PMID- 28983502 TI - Social Determinants of HIV/HCV Co-Infection: A case Study from People Who Inject Drugs in Rural Puerto Rico. PMID- 28983503 TI - Alzheimer's disease genetic risk variants beyond APOE epsilon4 predict mortality. AB - INTRODUCTION: We hypothesized that, like apolipoprotein E (APOE), other late onset Alzheimer's disease (LOAD) genetic susceptibility loci predict mortality. METHODS: We used a weighted genetic risk score (GRS) from 21 non-APOE LOAD risk variants to predict survival in the Adult Changes in Thought and the Health and Retirement Studies. We meta-analyzed hazard ratios and examined models adjusted for cognitive performance or limited to participants with dementia. For replication, we assessed the GRS-longevity association in the Cohorts for Heart and Aging Research in Genomic Epidemiology, comparing cases surviving to age >=90 years with controls who died between ages 55 and 80 years. RESULTS: Higher GRS predicted mortality (hazard ratio = 1.05; 95% confidence interval: 1.00-1.10, P = .04). After adjusting for cognitive performance or restricting to participants with dementia, the relationship was attenuated and no longer significant. In case control analysis, the GRS was associated with reduced longevity (odds ratio = 0.64; 95% confidence interval: 0.41-1.00, P = .05). DISCUSSION: Non-APOE LOAD susceptibility loci confer risk for mortality, likely through effects on dementia incidence. PMID- 28983504 TI - Perspectives on endoscopic surveillance of dysplasia in inflammatory bowel disease: a survey of academic gastroenterologists. AB - BACKGROUND AND STUDY AIMS: Dye-based chromoendoscopy (DBC) is the preferred method for endoscopic dysplasia surveillance in patients with inflammatory bowel disease (IBD). We sought to examine the uptake of, and perception toward DBC among academic gastroenterologists. METHODS: We conducted an online survey of academic members of the Canadian Association of Gastroenterology to assess their current dysplasia surveillance practice, uptake of DBC, and perceived barriers to adoption of DBC. RESULTS: Of the 150 physicians contacted, 49 (32.7 %) responded to the survey. The majority of respondents reported subspecialty training in IBD (71.4 %), and the median number of years in practice was 12. White-light endoscopy with random colonic biopsies was the preferred dysplasia screening method (73.5 %). Only 26.5 % of respondents routinely used DBC, despite institutional availability of over 60 %. The major barriers to adoption of DBC were concerns about procedure duration (46.9 %), concerns about cost (44.9 %), and inadequate training (40.8 %). CONCLUSION: There is low uptake of DBC for dysplasia surveillance in IBD patients among academic gastroenterologists practicing in Canada. Additional studies should be completed to determine how to improve the uptake of DBC. PMID- 28983505 TI - Comparison of endoscopic ultrasound-guided fine-needle aspiration by capillary action, suction, and no suction methods: a randomized blinded study. AB - BACKGROUND AND STUDY AIM : Different types of endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) techniques are used in clinical practice; the best method in terms of outcome has not been determined. The aim of the study was to compare the diagnostic adequacy of aspirated material, and the cytopathological and EUS morphological features between capillary action, suction, and no-suction FNA methods. PATIENTS AND METHODS: This was a prospective, single-blinded, randomized study conducted at a tertiary care hospital. Patients were randomized to the three groups: capillary action, suction, and no suction. A total of 300 patients were included, with 100 patients in each arm. RESULTS: A total of 300 patients (195 males) underwent EUS-FNA of 235 lymph nodes and 65 pancreatic masses (distribution not statistically different between the groups). The mean age was 52 +/- 14 years. A 22 gauge needle was used in the majority (93 %) of procedures. There was no statistical difference between the three groups regarding lymph node size at the largest axis and ratio, type of needle, echo features, echogenicity, calcification, necrosis, shape, borders (lymph nodes), number of passes, and cellularity. Diagnostic adequacy of the specimen was 91 %, 91 %, and 94 % in the capillary, suction, and no suction groups, respectively ( P = 0.67). Significantly more slides and blood clots were generated by the suction method compared with the other methods. CONCLUSION: The capillary action, suction, and no suction methods of EUS-FNA are similar in terms of diagnostic adequacy of the specimen. The suction method has the disadvantages of causing more bleeding and generating more slides. PMID- 28983506 TI - Newly recognized turbidity current structure can explain prolonged flushing of submarine canyons. AB - Seabed-hugging flows called turbidity currents are the volumetrically most important process transporting sediment across our planet and form its largest sediment accumulations. We seek to understand the internal structure and behavior of turbidity currents by reanalyzing the most detailed direct measurements yet of velocities and densities within oceanic turbidity currents, obtained from weeklong flows in the Congo Canyon. We provide a new model for turbidity current structure that can explain why these are far more prolonged than all previously monitored oceanic turbidity currents, which lasted for only hours or minutes at other locations. The observed Congo Canyon flows consist of a short-lived zone of fast and dense fluid at their front, which outruns the slower moving body of the flow. We propose that the sustained duration of these turbidity currents results from flow stretching and that this stretching is characteristic of mud-rich turbidity current systems. The lack of stretching in previously monitored flows is attributed to coarser sediment that settles out from the body more rapidly. These prolonged seafloor flows rival the discharge of the Congo River and carry ~2% of the terrestrial organic carbon buried globally in the oceans each year through a single submarine canyon. Thus, this new structure explains sustained flushing of globally important amounts of sediment, organic carbon, nutrients, and fresh water into the deep ocean. PMID- 28983508 TI - Specific reduction in cortisol stress reactivity after social but not attention based mental training. AB - Psychosocial stress is a public health burden in modern societies. Chronic stress induced disease processes are, in large part, mediated via the activation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic-adrenal-medullary system. We asked whether the contemplative mental training of different practice types targeting attentional, socio-affective (for example, compassion), or socio cognitive abilities (for example, perspective-taking) in the context of a 9-month longitudinal training study offers an effective means for psychosocial stress reduction. Using a multimethod approach including subjective, endocrine, autonomic, and immune markers and testing 313 participants in a standardized psychosocial laboratory stressor, we show that all three practice types markedly reduced self-reported stress reactivity in healthy participants. However, only the training of intersubjective skills via socio-affective and socio-cognitive routes attenuated the physiological stress response, specifically the secretion of the HPA axis end-product cortisol, by up to 51%. The assessed autonomic and innate immune markers were not influenced by any practice type. Mental training focused on present-moment attention and interoceptive awareness as implemented in many mindfulness-based intervention programs was thus limited to stress reduction on the level of self-report. However, its effectiveness was equal to that of intersubjective practice types in boosting the association between subjective and endocrine stress markers. Our results reveal a broadly accessible low-cost approach to acquiring psychosocial stress resilience. Short daily intersubjective practice may be a promising method for minimizing the incidence of chronic social stress-related disease, thereby reducing individual suffering and relieving a substantial financial burden on society. PMID- 28983507 TI - Structural plasticity of the social brain: Differential change after socio affective and cognitive mental training. AB - Although neuroscientific research has revealed experience-dependent brain changes across the life span in sensory, motor, and cognitive domains, plasticity relating to social capacities remains largely unknown. To investigate whether the targeted mental training of different cognitive and social skills can induce specific changes in brain morphology, we collected longitudinal magnetic resonance imaging (MRI) data throughout a 9-month mental training intervention from a large sample of adults between 20 and 55 years of age. By means of various daily mental exercises and weekly instructed group sessions, training protocols specifically addressed three functional domains: (i) mindfulness-based attention and interoception, (ii) socio-affective skills (compassion, dealing with difficult emotions, and prosocial motivation), and (iii) socio-cognitive skills (cognitive perspective-taking on self and others and metacognition). MRI-based cortical thickness analyses, contrasting the different training modules against each other, indicated spatially diverging changes in cortical morphology. Training of present-moment focused attention mostly led to increases in cortical thickness in prefrontal regions, socio-affective training induced plasticity in frontoinsular regions, and socio-cognitive training included change in inferior frontal and lateral temporal cortices. Module-specific structural brain changes correlated with training-induced behavioral improvements in the same individuals in domain-specific measures of attention, compassion, and cognitive perspective taking, respectively, and overlapped with task-relevant functional networks. Our longitudinal findings indicate structural plasticity in well-known socio affective and socio-cognitive brain networks in healthy adults based on targeted short daily mental practices. These findings could promote the development of evidence-based mental training interventions in clinical, educational, and corporate settings aimed at cultivating social intelligence, prosocial motivation, and cooperation. PMID- 28983509 TI - Multicellularity enriches the entrainment of Arabidopsis circadian clock. AB - The phase response curve (PRC) of the circadian clock provides one of the most significant indices for anticipating entrainment of outer cycles, despite the difficulty of making precise PRC determinations in experiments. We characterized the PRC of the Arabidopsisthaliana circadian clock on the basis of its phase locking property to variable periodic pulse perturbations. Experiments revealed that the PRC changed remarkably from continuous to discontinuous fashion, depending on the oscillation amplitude. Our hypothesis of amplitude-dependent adaptability to outer cycles was successfully clarified by elucidation of this transition of PRC as a change in the collective response of the circadian oscillator network. These findings provide an essential criterion against which to evaluate the precision of PRC measurement and an advanced understanding of the adaptability of plant circadian systems to environmental conditions. PMID- 28983510 TI - Mountain glaciation drives rapid oxidation of rock-bound organic carbon. AB - Over millions of years, the oxidation of organic carbon contained within sedimentary rocks is one of the main sources of carbon dioxide to the atmosphere, yet the controls on this emission remain poorly constrained. We use rhenium to track the oxidation of rock-bound organic carbon in the mountain watersheds of New Zealand, where high rates of physical erosion expose rocks to chemical weathering. Oxidative weathering fluxes are two to three times higher in watersheds dominated by valley glaciers and exposed to frost shattering processes, compared to those with less glacial cover; a feature that we also observe in mountain watersheds globally. Consequently, we show that mountain glaciation can result in an atmospheric carbon dioxide source during weathering and erosion, as fresh minerals are exposed for weathering in an environment with high oxygen availability. This provides a counter mechanism against global cooling over geological time scales. PMID- 28983511 TI - Risk preference shares the psychometric structure of major psychological traits. AB - To what extent is there a general factor of risk preference, R, akin to g, the general factor of intelligence? Can risk preference be regarded as a stable psychological trait? These conceptual issues persist because few attempts have been made to integrate multiple risk-taking measures, particularly measures from different and largely unrelated measurement traditions (self-reported propensity measures assessing stated preferences, incentivized behavioral measures eliciting revealed preferences, and frequency measures assessing actual risky activities). Adopting a comprehensive psychometric approach (1507 healthy adults completing 39 risk-taking measures, with a subsample of 109 participants completing a retest session after 6 months), we provide a substantive empirical foundation to address these issues, finding that correlations between propensity and behavioral measures were weak. Yet, a general factor of risk preference, R, emerged from stated preferences and generalized to specific and actual real-world risky activities (for example, smoking). Moreover, R proved to be highly reliable across time, indicative of a stable psychological trait. Our findings offer a first step toward a general mapping of the construct risk preference, which encompasses both general and domain-specific components, and have implications for the assessment of risk preference in the laboratory and in the wild. PMID- 28983512 TI - Gentle reenergization of electrons in merging galaxy clusters. AB - Galaxy clusters are the most massive constituents of the large-scale structure of the universe. Although the hot thermal gas that pervades galaxy clusters is relatively well understood through observations with x-ray satellites, our understanding of the nonthermal part of the intracluster medium (ICM) remains incomplete. With Low-Frequency Array (LOFAR) and Giant Metrewave Radio Telescope (GMRT) observations, we have identified a phenomenon that can be unveiled only at extremely low radio frequencies and offers new insights into the nonthermal component. We propose that the interplay between radio-emitting plasma and the perturbed intracluster medium can gently reenergize relativistic particles initially injected by active galactic nuclei. Sources powered through this mechanism can maintain electrons at higher energies than radiative aging would allow. If this mechanism is common for aged plasma, a population of mildly relativistic electrons can be accumulated inside galaxy clusters providing the seed population for merger-induced reacceleration mechanisms on larger scales such as turbulence and shock waves. PMID- 28983513 TI - Potentiating antibiotics in drug-resistant clinical isolates via stimuli activated superoxide generation. AB - The rise of multidrug-resistant (MDR) bacteria is a growing concern to global health and is exacerbated by the lack of new antibiotics. To treat already pervasive MDR infections, new classes of antibiotics or antibiotic adjuvants are needed. Reactive oxygen species (ROS) have been shown to play a role during antibacterial action; however, it is not yet understood whether ROS contribute directly to or are an outcome of bacterial lethality caused by antibiotics. We show that a light-activated nanoparticle, designed to produce tunable flux of specific ROS, superoxide, potentiates the activity of antibiotics in clinical MDR isolates of Escherichia coli, Salmonella enterica, and Klebsiella pneumoniae. Despite the high degree of antibiotic resistance in these isolates, we observed a synergistic interaction between both bactericidal and bacteriostatic antibiotics with varied mechanisms of action and our superoxide-producing nanoparticles in more than 75% of combinations. As a result of this potentiation, the effective antibiotic concentration of the clinical isolates was reduced up to 1000-fold below their respective sensitive/resistant breakpoint. Further, superoxide generating nanoparticles in combination with ciprofloxacin reduced bacterial load in epithelial cells infected with S. enterica serovar Typhimurium and increased Caenorhabditis elegans survival upon infection with S. enterica serovar Enteriditis, compared to antibiotic alone. This demonstration highlights the ability to engineer superoxide generation to potentiate antibiotic activity and combat highly drug-resistant bacterial pathogens. PMID- 28983514 TI - Effective drug combination for Caenorhabditis elegans nematodes discovered by output-driven feedback system control technique. AB - Infections from parasitic nematodes (or roundworms) contribute to a significant disease burden and productivity losses for humans and livestock. The limited number of anthelmintics (or antinematode drugs) available today to treat these infections are rapidly losing their efficacy as multidrug resistance in parasites becomes a global health challenge. We propose an engineering approach to discover an anthelmintic drug combination that is more potent at killing wild-type Caenorhabditis elegans worms than four individual drugs. In the experiment, freely swimming single worms are enclosed in microfluidic drug environments to assess the centroid velocity and track curvature of worm movements. After analyzing the behavioral data in every iteration, the feedback system control (FSC) scheme is used to predict new drug combinations to test. Through a differential evolutionary search, the winning drug combination is reached that produces minimal centroid velocity and high track curvature, while requiring each drug in less than their EC50 concentrations. The FSC approach is model-less and does not need any information on the drug pharmacology, signaling pathways, or animal biology. Toward combating multidrug resistance, the method presented here is applicable to the discovery of new potent combinations of available anthelmintics on C. elegans, parasitic nematodes, and other small model organisms. PMID- 28983515 TI - Using Research-Informed Pedagogical Practices to Maximize Learning in Youth Cognitive Behavioral Therapy. AB - Cognitive-behavioral therapy (CBT) for youth is an evidence-based treatment that typically starts with some form of psychoeducation, during which the patient is taught in a didactic manner about their presenting problems and strategies to ameliorate their symptoms. The learning process continues over the course of treatment as patients consolidate and attempt to utilize their aqcuired knowledge in their daily life. Manuals provide helpful structure and strategies to facilitate this learning process (e.g., using metaphors, personalized coping cards); however, there is variability across patients in terms of what presented content they will be able to access and understand, how they can most effectively transfer what they learn into their everyday life, and why they will become engaged in this learning process. The purpose of this paper is to connect CBT and pedagogy by outlining the research-informed pedagogical framework known as Universal Design for Learning (UDL) as it relates to the teaching and learning that takes place in CBT. First, we describe UDL as a lens through which clinicians can conceptualize evidence-based pedagogical principles that undergird common CBT teaching practices. Second, we recommend that clinicians use UDL as a guiding framework when they are faced with barriers to learning due to the variability that exists in how patients engage in, access and understand, and utilize the material. We posit that UDL can help clinicians ensure that more patients are able to successfully access and benefit from CBT. PMID- 28983516 TI - A biologist's guide to Bayesian phylogenetic analysis. AB - Bayesian methods have become very popular in molecular phylogenetics due to the availability of user-friendly software implementing sophisticated models of evolution. However, Bayesian phylogenetic models are complex, and analyses are often carried out using default settings, which may not be appropriate. Here, we summarize the major features of Bayesian phylogenetic inference and discuss Bayesian computation using Markov chain Monte Carlo (MCMC), the diagnosis of an MCMC run, and ways of summarising the MCMC sample. We discuss the specification of the prior, the choice of the substitution model, and partitioning of the data. Finally, we provide a list of common Bayesian phylogenetic software and provide recommendations as to their use. PMID- 28983517 TI - Competing species leave many potential niches unfilled. AB - A cornerstone of biology is that coexisting species evolve to occupy separate ecological niches. Classical theory predicts that interspecific competition should lead to all potential niches being occupied, yet observational data suggest that many niches are unfilled. Here we show that theory can be reconciled with observational data by reconceptualising competition in the Hutchinsonian niche space to distinguish between substitutable and non-substitutable resources. When resources are substitutable (e.g. seeds of different size), the components of competition along the niche axes combine multiplicatively, leading to a densely packed niche space. However, when resources are non-substitutable (e.g. seeds and nest sites), we show that the components of competition combine additively. Disruptive selection therefore limits niche overlap between non substitutable niche axes, leaving most potential niches unfilled. A key corollary is that increasing the number of niche axes may greatly increase the number of potential niches but does not necessarily increase diversity. We discuss observational data that are consistent with our model and consider implications for systems with invasive species. Our work reinforces the power of competition to drive major ecological patterns: while niche space informs on species that might exist, only a small and potentially arbitrary subset will coexist in sympatry. PMID- 28983520 TI - Cross-hierarchy systems principles. AB - One driving motivation of systems biology is the search for general principles that govern the design of biological systems. But questions often arise as to what kind of general principles biology could have. Concepts from engineering such as robustness and modularity are indeed becoming a regular way of describing biological systems. Another source of potential general principles is the emerging similarities found in processes across biological hierarchies. In this piece, I describe several emerging cross-hierarchy similarities. Identification of more cross-hierarchy principles, and understanding the implications these convergence have on the construction of biological systems, I believe, present exciting challenges for systems biology in the decades to come. PMID- 28983519 TI - Neuroticism and Individual Differences in Neural Function in Unmedicated Major Depression: Findings from the EMBARC Study. AB - BACKGROUND: Personality dysfunction represents one of the only predictors of differential response between active treatments for depression to have replicated. In this study, we examine whether depressed patients with higher neuroticism scores, a marker of personality dysfunction, show differences versus depressed patients with lower scores in the functioning of two brain regions associated with treatment response, the anterior cingulate and anterior insula cortices. METHODS: Functional magnetic resonance imaging data during an emotional Stroop task were collected from 135 adults diagnosed with major depressive disorder at four academic medical centers participating in the Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) study. Secondary analyses were conducted including a sample of 28 healthy individuals. RESULTS: In whole-brain analyses, higher neuroticism among depressed adults was associated with increased activity in and connectivity with the right anterior insula cortex to incongruent compared to congruent emotional stimuli (ks>281, ps<0.05 FWE corrected), covarying for concurrent psychiatric distress. We also observed an unanticipated relationship between neuroticism and reduced activity in the precuneus (k=269, p<0.05 FWE corrected). Exploratory analyses including healthy individuals suggested that associations between neuroticism and brain function may be nonlinear over the full range of neuroticism scores. CONCLUSIONS: This study provides convergent evidence for the importance of the right anterior insula cortex as a brain-based marker of clinically meaningful individual differences in neuroticism among adults with depression. This is a critical next step in linking personality dysfunction, a replicated clinical predictor of differential antidepressant treatment response, with differences in underlying brain function. PMID- 28983518 TI - Evidence for a Large-Scale Brain System Supporting Allostasis and Interoception in Humans. AB - Large-scale intrinsic brain systems have been identified for exteroceptive senses (e.g., sight, hearing, touch). We introduce an analogous system for representing sensations from within the body, called interoception, and demonstrate its relation to regulating peripheral systems in the body, called allostasis. Employing the recently introduced Embodied Predictive Interoception Coding (EPIC) model, we used tract-tracing studies of macaque monkeys, followed by two intrinsic functional magnetic resonance imaging samples (N = 280 and N = 270) to evaluate the existence of an intrinsic allostatic/interoceptive system in the human brain. Another sample (N = 41) allowed us to evaluate the convergent validity of the hypothesized allostatic/interoceptive system by showing that individuals with stronger connectivity between system hubs performed better on an implicit index of interoceptive ability related to autonomic fluctuations. Implications include insights for the brain's functional architecture, dissolving the artificial boundary between mind and body, and unifying mental and physical illness. PMID- 28983521 TI - Topological methods for genomics: present and future directions. AB - Topological methods are emerging as a new set of tools for the analysis of large genomic datasets. They are mathematically grounded methods that extract information from the geometric structure of data. In the last few years, applications to evolutionary biology, cancer genomics, and the analysis of complex diseases have uncovered significant biological results, highlighting their utility for fulfilling some of the current analytic needs of genomics. In this review, the state of the art in the application of topological methods to genomics is summarized, and some of the present limitations and possible future developments are reviewed. PMID- 28983522 TI - Solvent Vapor Annealing of Amorphous Carbamazepine Films for Fast Polymorph Screening and Dissolution Alteration. AB - Solubility enhancement and thus higher bioavailability are of great importance and a constant challenge in pharmaceutical research whereby polymorph screening and selection is one of the most important tasks. A very promising approach for polymorph screening is solvent vapor annealing where a sample is exposed to an atmosphere saturated with molecules of a specific chemical/solvent. In this work, amorphous carbamazepine thin films were prepared by spin coating, and the transformation into crystalline forms under exposure to solvent vapors was investigated. Employing grazing incidence X-ray diffraction, four distinct carbamazepine polymorphs, a solvate, and hydrates could be identified, while optical microscopy showed mainly spherulitic morphologies. In vitro dissolution experiments revealed different carbamazepine release from the various thin-film samples containing distinct polymorphic compositions: heat treatment of amorphous samples at 80 degrees C results in an immediate release; samples exposed to EtOH vapors show a drug release about 5 times slower than this immediate one; and all the others had intermediate release profiles. Noteworthy, even the sample of slowest release has a manifold faster release compared to a standard powder sample demonstrating the capabilities of thin-film preparation for faster drug release in general. Despite the small number of samples in this screening experiment, the results clearly show how solvent vapor annealing can assist in identifying potential polymorphs and allows for estimating their impact on properties like bioavailability. PMID- 28983523 TI - Glycoamino Acid Analogues of the Thomsen-Friedenreich Tumor-Associated Carbohydrate Antigen: Synthesis and Evaluation of Novel Antiproliferative Factor Glycopeptides. AB - Glycoamino acid analogues of the Thomsen-Friedenreich antigen disaccharide, where the 4' and 4" hydroxyl groups were substituted with fluorine or hydrogen, were synthesized and incorporated into the asialylated antiproliferative factor (as APF), a biologically active form of APF, a glycopeptide found in the urine of patients with interstitial cystitis. Various strategies were employed to incorporate the fluorine atom at the 4-positions of either the galactose or N acetylgalactosamine unit of the disaccharide antigen, based on stereochemistry and reactivity. These glycopeptides were evaluated in antiproliferative assays on both primary normal bladder epithelial cells and T24 bladder carcinoma cells. Unlike many previously published substitutions to APF, mono-4'-fluorination of the GalNAc residue did not affect the activity, whereas fluoro-derivatives of the galactose 4"-position or both 4' and 4" hydroxyls showed a reduced potency relative to the monosubstituted GalNAc derivative. A fourth compound where the 4" position of galactose was deoxygenated showed a lower potency than the parent and monosubstituted compounds. These results suggest that specific substitutions in the sugar moieties in the APF can be tolerated, and the glycomimetic design of APF analogues can include fluorine in the GalNAc sugar of the disaccharide. PMID- 28983524 TI - Low-Temperature Electron Beam-Induced Transformations of Cesium Lead Halide Perovskite Nanocrystals. AB - Cesium lead halide perovskite (CsPbX3, with X = Br, Cl, I) nanocrystals have been found to undergo severe modifications under the high-energy electron beam irradiation of a transmission electron microscope (80/200 keV). In particular, in our previous work, together with halogen desorption, Pb2+ ions were found to be reduced to Pb0 and then diffused to form lead nanoparticles at temperatures above -40 degrees C. Here, we present a detailed irradiation study of CsPbBr3 nanocrystals at temperatures below -40 degrees C, a range in which the diffusion of Pb0 atoms/clusters is drastically suppressed. Under these conditions, the irradiation instead induces the nucleation of randomly oriented CsBr, CsPb, and PbBr2 crystalline domains. In addition to the Br desorption, which accompanies Pb2+ reduction at all the temperatures, Br is also desorbed from the CsBr and PbBr2 domains at low temperatures, leading to a more pronounced Br loss, thus the final products are mainly composed of Cs and Pb. The overall transformation involves the creation of voids, which coalesce upon further exposure, as demonstrated in both nanosheets and nanocuboids. Our results show that although low temperatures hinder the formation of Pb nanoparticles in CsPbBr3 nanocrystals when irradiated, the nanocrystals are nevertheless unstable. Consequently, we suggest that an optimum combination of temperature range, electron energy, and dose rate needs to be carefully chosen for the characterization of halide perovskite nanocrystals to minimize both the Pb nanoparticle formation and the structural decomposition. PMID- 28983525 TI - Exploiting the 2-Amino-1,3,4-thiadiazole Scaffold To Inhibit Trypanosoma brucei Pteridine Reductase in Support of Early-Stage Drug Discovery. AB - Pteridine reductase-1 (PTR1) is a promising drug target for the treatment of trypanosomiasis. We investigated the potential of a previously identified class of thiadiazole inhibitors of Leishmania major PTR1 for activity against Trypanosoma brucei (Tb). We solved crystal structures of several TbPTR1-inhibitor complexes to guide the structure-based design of new thiadiazole derivatives. Subsequent synthesis and enzyme- and cell-based assays confirm new, mid micromolar inhibitors of TbPTR1 with low toxicity. In particular, compound 4m, a biphenyl-thiadiazole-2,5-diamine with IC50 = 16 MUM, was able to potentiate the antitrypanosomal activity of the dihydrofolate reductase inhibitor methotrexate (MTX) with a 4.1-fold decrease of the EC50 value. In addition, the antiparasitic activity of the combination of 4m and MTX was reversed by addition of folic acid. By adopting an efficient hit discovery platform, we demonstrate, using the 2 amino-1,3,4-thiadiazole scaffold, how a promising tool for the development of anti-T. brucei agents can be obtained. PMID- 28983526 TI - An Ideal C3-Symmetric Sulfate Complex: Molecular Recognition of Oxoanions by m Nitrophenyl- and Pentafluorophenyl-Functionalized Hexaurea Receptors. AB - The anion-binding properties of two tripodal-based hexaureas appended with the m nitrophenyl (1) and pentafluorophenyl (2) groups have been studied both experimentally and theoretically, showing strong affinities for sulfate over other inorganic oxoanions such as hydrogen sulfate, dihydrogen phosphate, bicarbonate, nitrate, and perchlorate. The structural analysis of the sulfate complex with 1 reveals that the receptor organizes all urea-binding sites toward the cavity at precise orientations around a tetrahedral sulfate anion to form an ideal C3-symmetric sulfate complex that is stabilized by 12 hydrogen-bonding interactions. The receptor and the encapsulated sulfate are located on the threefold axis passing through the bridgehead nitrogen of 1 and the sulfur atom of the anionic guest. The high-level density functional theory calculations support the crystallographic results, demonstrating that the C3-symmetric conformation of the sulfate complex is achieved due to the complementary NH...O between the receptor and sulfate. PMID- 28983527 TI - Microwave Heating of Crystals with Gold Nanoparticles and Synovial Fluid under Synthetic Skin Patches. AB - Gout is a disease with elusive treatment options. Reduction of the size of l alanine crystals as a model crystal for gouty tophi with the use of a monomode solid-state microwave was examined as a possible therapeutic aid. The effect of microwave heating on l-alanine crystals in the presence of gold nanoparticles (Au NPs) in solution and synovial fluid (SF) in a plastic pouch through a synthetic skin patch was investigated. In this regard, three experimental paradigms were employed: Paradigm 1 includes the effect of variable microwave power (5-10 W) and variable heating time (5-60 s) and Au NPs in water (20 nm size, volume of 10 MUL) in a plastic pouch (1 * 2 cm2 in size). Paradigm 2 includes the effect of a variable volume of 20 nm Au NPs in a variable volume of SF up to 100 MUL in a plastic pouch at a constant microwave power (10 W) for 30 s. Paradigm 3 includes the effect of constant microwave power (10 W) and microwave heating time (30 s), constant volume of Au NPs (100 MUL), and variable size of Au NPs (20-200 nm) placed in a plastic pouch through a synthetic skin patch. In these experiments, an average of 60-100% reduction in the size of an l-alanine crystal (initial size = 450 MUm) without damage to the synthetic skin or increasing the temperature of the samples beyond the physiological range was reported. PMID- 28983529 TI - Editorial: IJED and the Accademia Italiana di Odontoiatria Conservativa e Restaurativa. PMID- 28983528 TI - Toxicant Formation in Dabbing: The Terpene Story. AB - Inhalable, noncombustible cannabis products are playing a central role in the expansion of the medical and recreational use of cannabis. In particular, the practice of "dabbing" with butane hash oil has emerged with great popularity in states that have legalized cannabis. Despite their growing popularity, the degradation product profiles of these new products have not been extensively investigated. The study herein focuses on the chemistry of myrcene and other common terpenes found in cannabis extracts. Methacrolein, benzene, and several other products of concern to human health were formed under the conditions that simulated real-world dabbing. The terpene degradation products observed are consistent with those reported in the atmospheric chemistry literature. PMID- 28983530 TI - Ceramic laminate veneers: clinical procedures with a multidisciplinary approach. AB - Complex cases with high esthetic needs represent a challenge for clinicians. A multidisciplinary approach is vital to achieve the planned result. New technological devices are needed to facilitate the collaboration between the clinical team members and to develop a fluent and effective diagnostic and therapeutic pathway. This article describes a well-defined protocol for the treatment of complex esthetic cases with the use of ceramic laminate veneers. The protocol involves different branches of dentistry: periodontal therapy, mucogingival surgery, restorative dentistry, orthodontics, and prosthodontics. Each step of the protocol should be executed in a very strict order: intra- and extraoral esthetic analysis of the patient, with photographs; digital previsualization by means of Digital Smile Design (DSD); clinical previsualization by means of a mock-up; orthodontic, mucogingival, and endodontic treatments, if needed; minimally invasive tooth preparation, driven by a mock-up and silicone indices; manufacture of ceramic laminate veneers; try-in and adhesive cementation. In this article, this protocol is illustrated by a clinical case report in which all the above-mentioned steps were carried out. The finalization was obtained by means of state-of-the-art adhesive techniques and ceramic laminate veneers. The correct use of modern materials, in combination with rigorous adhesive procedures, allows for a minimally invasive and highly esthetic treatment, with adequate function and a perfect integration that is in harmony with the patient's face. PMID- 28983531 TI - The "index cutback technique": a three-dimensional guided layering approach in direct class IV composite restorations. AB - One of the main difficulties encountered with conventional class IV direct composite restorations is the layering management in terms of three dimensionality and shape control. The major concern is the predictability of the esthetic outcome, which is closely linked to the clinician's skills. This article presents a predictable approach to treat class IV direct composite restorations. The technique allows for the shape and thickness of different composite layers to be guided through transparent indexes that have been carried out previously on a planned wax-up. The final goal is to achieve a good esthetic outcome in an easy and fast way through a copy-and-paste approach. The "index cutback technique" is a complementary variant of the "index technique" for class IV direct restorations. After the casts have been generated, the technician creates a full wax-up of the tooth to be restored. A transparent silicone key of the full wax-up provides the full enamel index that is then cut with a blade along the incisal edge to achieve two enamel indexes, one palatal and one buccal. Then, the required amount of wax is removed from the full wax-up through a cutback step. The aim of this step is to remove a suitable amount of wax to leave a predetermined space for the composite enamel layers, both on the palatal and buccal surfaces. A second transparent silicone key is built on the cutback wax-up to achieve the cutback dentin index, which is then used to press the composite dentin onto the prepared tooth. PMID- 28983532 TI - Direct composites in anteriors: a matter of substrate. AB - When planning a restoration, the color of the substrate should also be taken into account in order to achieve a satisfactory esthetic outcome. In some clinical situations, clinicians are asked to hide the substrate with the restoration; in other situations, clinicians can take advantage of an unaltered color substrate and therefore select less opaque materials that exploit the color of the underlying tissue. PMID- 28983533 TI - Posterior indirect adhesive restorations (PIAR): preparation designs and adhesthetics clinical protocol. AB - Posterior indirect adhesive restorations (PIAR) are very common nowadays in clinical practice. The indirect approach is often indicated by a need for cuspal coverage (one or more cusps). With the adhesthetics protocol, the first step is to perform a cavity analysis evaluating the resistance of the tooth after restoration. The structures to be evaluated are, in sequence, the interaxial dentin, ridges, roof of the pulp chamber, and cusps. To improve the strength, the cusps should be covered, when required. The build-up for PIAR is performed with an adhesive technique, and, if possible, with low-shrinkage materials. The use of an adhesive post is not required, but not contraindicated if performed with a conservative approach on the root canal. Different preparation designs can be chosen. The butt joint, the most common with an adhesive technique, is used to protect the cusp when it is evaluated to be too fragile. A variant of the butt joint, the bevel, is useful for esthetic purposes or for providing more space or more enamel surface on the peripheral part of the preparation. The shoulder is useful if a cervical grasp is required, but is usually indicated when a previous cusp fracture needs to be restored. The veneerlay combines an overlay design with a buccal veneer when there are specific esthetic needs. In the interproximal areas, the preparation designs can be classified as: slot - the most common; bevel - useful in some cases to restore the ridge with a more conservative approach; ridge up - useful to preserve the ridge (a very important structure to maintain the resistance of the tooth) even when cuspal coverage is required. Ridge up can have two variants: ridge preservation and ridge coverage. More than one preparation design is used in many cases in the same preparation, taking into consideration the specific situation of the tooth and its different areas, in order to balance the prognosis with a conservative approach. PMID- 28983534 TI - From orthodontic treatment plan to ultrathin no-prep CAD/CAM temporary veneers. AB - Several treatment options are described in the literature to solve the microdontia-related problems of maxillary anterior teeth. These options are often focused on an orthodontic rather than a restorative approach. The case presented here started with an orthodontic phase followed by a restorative one. The aim of the orthodontic phase was to achieve the correct spacing, respecting ideal average tooth proportions. This was done using a digital setup to restore the six anterior teeth, so that an optimal esthetic and functional result was achieved by the end of the orthodontic treatment. The purpose of the restorative phase was to contribute to the esthetic outcome and occlusal stability. The 12-year-old patient was treated utilizing a CAD/CAM procedure, which took advantage of the mechanical properties and reasonable cost of the chosen resin matrix ceramic material (Vita Enamic). Once stability has been attained and proper periodontal tissue maturation has been reached at the end of the patient's growth, there will then be the option of improving the esthetics by replacing these restorations with ceramic veneers. PMID- 28983535 TI - New adhesives and bonding techniques. Why and when? AB - Nowadays, adhesive dentistry is a fundamental part of daily clinical work. The evolution of adhesive materials and techniques has been based on the need for simplicity in the step-by-step procedures to obtain long-lasting direct and indirect restorations. For this reason, recently introduced universal multimode adhesives represent a simple option for creating a hybrid layer, with or without the use of phosphoric acid application. However, it is important to understand the limitations of this latest generation of adhesive systems as well as how to use them on coronal and radicular dentin. Based on the findings in the literature, universal multimode adhesives have shown promising results, even if the problem of hybrid layer degradation due to the hydrolytic activity of matrix metalloproteinases (MMPs) still exists. Studies are therefore required to help us understand how to reduce this degradation. PMID- 28983536 TI - Visible light-driven, magnetically steerable gold/iron oxide nanomotors. AB - We report the synthesis and properties of rod-shaped gold/iron oxide nanomotors that are powered by visible light in dilute hydrogen peroxide solutions. Electrochemical measurements confirmed that the light-driven nanomotors operate by a self-electrophoretic mechanism, modulated by the photovoltage and the photoconductivity of gold/iron oxide. Due to the magnetism of iron oxide, the nanomotors can be steered by an external magnetic field without incorporating additional magnetic materials into the nanomotors. PMID- 28983537 TI - Dynamic encapsulation of corannulene molecules into a single-walled carbon nanotube. AB - The morphology of corannulene molecules encapsulated in a single-walled carbon nanotube (SWCNT) is addressed using atomistic simulations. Firstly, dynamic simulation (DS) of encapsulation of corannulene molecules into a SWCNT is performed using a molecular dynamics (MD) method. It is revealed that corannulene molecules encapsulated in a SWCNT tend to form concave-concave (CC) dimers, and these dimers make stacks tilting against the SWCNT axis or take an arrangement such that their convex surfaces face the inner wall of the SWCNT. This tendency arises from the fact that the van der Waals interactions between the convex surfaces of the corannulene molecules and the inner wall of the SWCNT dominate in their dynamic encapsulation into the SWCNT, and CC dimers are favored based on the energetics. Next, conjugate gradient (CG) energy minimizations starting from two kinds of initial arrangement of corannulene molecules in a SWCNT, concave convex (CV) and CC/convex-convex (VV) arrangements, are performed. The CG energy minimizations confirm the result of DS that CC dimers are the structural motif of corannulene molecules in a SWCNT. From the final configurations of both the simulations, the tilt angles and intermolecular distances of the stacked molecules are calculated. With increasing the SWCNT diameter, the tilt angles decrease while the intermolecular distances remain almost constant. The tilt angles of the stacked corannulene molecules are approximately expressed by a semi analytical formula which is derived on the basis of a geometrical constraint condition. PMID- 28983538 TI - Ligand displacement induced morphologies in block copolymer/quantum dot hybrids and formation of core-shell hybrid nanoobjects. AB - We investigate the self-assembly of a cylinder-forming polystyrene-block-poly(4 vinylpyridine) (PS-b-P4VP) block copolymer (BCP) mixed with trioctylphosphine oxide (TOPO) capped cadmium selenide (CdSe) quantum dots (QDs). The QDs were found to be enthalpically compatible with the P4VP chains via ligand displacement of TOPO from the QD surface. However, the QDs were found to localize preferentially at the PS/P4VP interphase plausibly to gain translational entropy in order to further lower the energetics of the self-assembled structure. Interestingly, the morphological transformation observed with increasing weight fraction of the QDs in the BCP/QD composite was driven by the migration of the displaced TOPO from the QD surface to the PS phase, effectively increasing its total volume fraction. Hence, the PS-b-P4VP BCP with PS as the minority block displayed lamellar morphology in its composite with QDs. Furthermore, the preferred localization of the QDs at the PS/P4VP interface led to the formation of a trilayer lamellar morphology which was deduced from the suppression of the primary scattering peak, relative to higher order peaks in the SAXS data. The morphological transformation was accompanied by a significant increase in the domain spacing due to excessive stretching of the longer P4VP chains of the asymmetric block copolymer. However, in the PS-b-P4VP/CdSe composites with P4VP as the minority block, cylindrical morphology was retained and the domain spacing decreased due to dominance of the co-surfactant effect as well as interfacial localization of CdSe QDs. We also demonstrate that these PS-b-P4VP/CdSe self assembled hybrid materials could further be used to obtain isolated core-shell nanoobjects, such as nanofibers and nanosheets, containing CdSe QDs. The nanoobjects so obtained exhibited photoluminescence properties typical of CdSe quantum dots. These photoluminescent polymer nanoobjects could have potential applications in biological targeting and fluorescence labeling. PMID- 28983539 TI - A bowl-shaped sumanene derivative with dense convex-concave columnar packing for high-performance organic field-effect transistors. AB - The charge transport properties of a bowl-shaped sumanene derivative with dense convex-concave columnar packing were studied. Single-crystal microribbons were grown by solution casting. Organic field-effect transistors based on individual single-crystal ribbons displayed a high hole mobility up to 0.37 cm2 V-1 s-1, which was one of the highest mobilities for buckybowl aromatics. PMID- 28983540 TI - Enhancing thermoelectric performance of Cu2Se by doping Te. AB - Owing to the excellent electrical properties and inherently complex crystal structure, Cu2Se has been considered as a promising thermoelectric (TE) material. Herein, a series of Cu2Se1-xTex (x = 0, 0.02, 0.04, 0.06, and 0.08) bulk samples are prepared by combining mechanical alloying (MA) and spark plasma sintering (SPS) to investigate the effect of Te content (x) on the phase structure, microstructure and TE properties of stoichiometric Cu2Se. It is found that a maximum TE figure of merit (ZT) value of 1.25 could be achieved for Cu2Se0.98Te0.02 sample at 773 K, which essentially stemmed from the elevated power factor (PF) and reduced thermal conductivity (kappa). The results obtained in our study indicate that the introduction of Te into stoichiometric Cu2Se is an effective and convenient strategy to improve ZT by enhancing PF and decreasing kappa. PMID- 28983541 TI - What Mn Kbeta spectroscopy reveals concerning the oxidation states of the Mn cluster in photosystem II. AB - The oxygen evolving complex, (OEC) in Photosystem II contains a Mn4Ca cluster and catalyses oxidation of water to molecular oxygen and protons, the most energetically demanding reaction in nature. The catalytic mechanism remains unresolved and the precise Mn oxidation levels through which the cluster cycles during functional turnover are controversial. Two proposals for these redox levels exist; the 'high' and 'low' oxidation state paradigms, which differ systematically by two oxidation equivalents throughout the redox accumulating catalytic S state cycle (states S0...S3). Presently the 'high' paradigm is more favored. For S1 the assumed mean redox levels of Mn are 3.5 (high) and 3.0 (low) respectively. Mn K region X-ray spectroscopy has been extensively used to examine the OEC Mn oxidation levels, with Kbeta emission spectroscopy increasingly the method of choice. Here we review the results from application of this and closely related techniques to PS II, building on our earlier examination of these and other data on the OEC oxidation states (Pace et al., Dalton Trans., 2012, 41, 11145). We compare the most recent results with a range of earlier Mn Kbeta experiments on the photosystem and related model Mn systems. New analyses of these data are given, highlighting certain key spectral considerations which appear not to have been sufficiently appreciated earlier. These show that the recent and earlier PS II Kbeta results have a natural internal consistency, leading to the strong conclusion that the low paradigm oxidation state assignment for the functional OEC is favoured. PMID- 28983542 TI - A versatile covalent organic framework-based platform for sensing biomolecules. AB - We herein report the design of a versatile covalent organic framework (COF)-based platform for sensing biomolecules. As a proof of concept, a highly sensitive and selective COF-based fluorescence turn-on detection of DNA and adenosine 5' triphosphate is demonstrated. PMID- 28983544 TI - Temperature dependent evolution of wrinkled single-crystal silicon ribbons on shape memory polymers. AB - Shape memory polymers (SMPs) can remember two or more distinct shapes, and thus can have a lot of potential applications. This paper presents combined experimental and theoretical studies on the wrinkling of single-crystal Si ribbons on SMPs and the temperature dependent evolution. Using the shape memory effect of heat responsive SMPs, this study provides a method to build wavy forms of single-crystal silicon thin films on top of SMP substrates. Silicon ribbons obtained from a Si-on-insulator (SOI) wafer are released and transferred onto the surface of programmed SMPs. Then such bilayer systems are recovered at different temperatures, yielding well-defined, wavy profiles of Si ribbons. The wavy profiles are shown to evolve with time, and the evolution behavior strongly depends on the recovery temperature. At relatively low recovery temperatures, both wrinkle wavelength and amplitude increase with time as evolution progresses. Finite element analysis (FEA) accounting for the thermomechanical behavior of SMPs is conducted to study the wrinkling of Si ribbons on SMPs, which shows good agreement with experiment. Merging of wrinkles is observed in FEA, which could explain the increase of wrinkle wavelength observed in the experiment. This study can have important implications for smart stretchable electronics, wrinkling mechanics, stimuli-responsive surface engineering, and advanced manufacturing. PMID- 28983543 TI - Enabling electrical biomolecular detection in high ionic concentrations and enhancement of the detection limit thereof by coupling a nanofluidic crystal with reconfigurable ion concentration polarization. AB - The regulation effect of surface charges on the transport of electrons in nanomaterials and ions in nanofluidic devices has been widely used to develop highly sensitive and label-free electrical biosensors. The intrinsic limitation to the clinical application of surface charge-effect nano-electrical biosensors is that they usually do not function in physiological conditions normally with high ionic concentrations (~160 mM), in which the surface charges are screened within a short distance (<1 nm at 160 mM). In this work, we developed a general strategy that enables surface charge-effect electrical biomolecular detection in physiological conditions with an integrated mechanism for enhancement of the limit of detection (LOD) by in situ preconcentration of target molecules during incubation and creation of a transient low ionic concentration environment during the signal read-out step using reconfigurable ion concentration polarization (ICP). We demonstrated the effectiveness of this strategy in a simple nanofluidic biosensor named a nanofluidic crystal (NFC), which can be prepared within hours and without expensive equipment. Our results indicate that the ion depletion effect of ICP could lower the ionic concentration by at least 200 fold and provide a stable ionic environment for over 15 s, enabling electrical detection of proteins and DNAs in serum and urine with LODs of 1-10 nM. We further reconfigured the device to preconcentrate target biomolecules before detection using the enrichment effect of ICP, obtaining LODs of 10-100 pM for proteins and DNAs in physiological conditions. By overcoming the inherent constraint on buffer conditions and the issues regarding fabrication, we believe that this work represents significant progress towards the practical application of surface charge-effect nano-electrical biosensors in point-of-care diagnostics and clinical medicine. PMID- 28983545 TI - Electrolyte containing lithium cation in squaraine-sensitized solar cells: interactions and consequences for performance and charge transfer dynamics. AB - By optimizing the lithium concentration in an electrolyte to 50 mmol L-1 and the dye-to-chenodeoxycholic acid ratio in a VG1-based dye solution, we achieved 4.7% power conversion efficiency under standard AM 1.5G conditions. In addition to this performance, we herein discuss the role played by lithium in the electrolyte and its interplay in the charge transfer processes from ms to fs dynamics. Based on electrochemical impedance spectroscopy, photoluminescence and pump-probe transient absorption spectroscopy, we conclude that although lithium increases the electron diffusion length, this has no satisfactory impact on electron injection and even slows dye regeneration. This study provides evidence that lithium is not only specifically adsorbed on the surface of TiO2 but prompts a molecular reorganization of the self-assembled dye monolayer, forming harmful H aggregates. PMID- 28983546 TI - New sigma-phases in the Nb-X-Ga and Nb-X-Al systems (X = Ru, Rh, Pd, Ir, Pt, and Au). AB - Previously unreported sigma-phases in the ternary niobium-based systems Nb-X-Ga for X = Ru, Rh, Pd, Ir, Pt, Au, and Nb-X-Al for X = Ir, and Pt are presented, prepared by arc-melting followed by annealing at 1000 degrees C for 1 week. The phases are primitive tetragonal (P42/mnm, no. 136) with lattice parameters of a = 9.8336(2)-9.9432(1) A and c = 5.1098(1)-5.1718(1) A. Refinements of the single crystal X-ray diffraction data for the Ru and Ir containing materials gave the formulas Nb20Ru5Ga5 and Nb20Ir4Ga6, showing mixing of X/Ga on the crystallographic 8i2 and 2a sites of the structure, a type of disorder frequently found in sigma-phases. We present a graphical classification for ternary sigma phases that places our materials in context with previous materials. The materials do not show evidence of bulk superconductivity above 2 K. Synthesis of equivalent Ta-based sigma-phases was attempted but they were not found. PMID- 28983547 TI - Bismuth-rhodamine: a new red light-excitable photosensitizer. AB - Bismuth-rhodamine (BiR) was developed as a new photosensitizer scaffold, and its photophysical properties were evaluated. BiR showed significant red-shifted absorption and emission compared with other xanthene-based photosensitizers, together with an efficient quantum yield for the generation of 1O2. BiR showed efficient cell-permeability as well as photo-triggered generation of 1O2 in cells. PMID- 28983548 TI - Time-periodic oscillation reaction in an organic-solvent dominated electrolyte. AB - Time-periodic phenomena widely exist in natural life sustaining systems but are rarely reported in highly efficient artificial electrochemical energy-harvesting systems. Herein, we observed for the first time the periodic oscillation reaction in organic-solvent dominated electrolytes that could be also derived from some electrochemical energy harvesting cells. Owing to different reaction activity and acidity in the organic solvent, the oscillation reaction could occur under milder pH conditions and exhibit better durability. Its influence on electric output and related differences from an aqueous B-Z reaction are discussed from a mechanism point of view. Our findings may contribute to smart self-oscillation materials and new strategies for highly efficient long-term energy harvesting. PMID- 28983549 TI - Polycyclic aromatic hydrocarbons as model solutes for carbon nanomaterials in ionic liquids. AB - The aim of this work is to understand the details of the interactions of ionic liquids with carbon nanomaterials (graphene and nanotubes) using polyaromatic compounds as model solutes. We have combined the measurements of thermodynamic quantities of solvation with molecular dynamics simulations to provide a microscopic view. The solubility of five polycyclic aromatic hydrocarbons (naphthalene, anthracene, phenanthrene, pyrene and coronene) was determined in seven ionic liquids ([C4C1im][C(CN)3], [C4C1pyrr][Ntf2], [C10C1im][Ntf2], [C2C1im][C(CN)3], [C2C1im][Ntf2], [C3C1pyrr][N(CN)2] and [C4C1im][N(CN)2]) at 298 K. The enthalpies of the dissolution of naphthalene, anthracene and pyrene were measured in four of the ionic liquids. Free energies were estimated from those measurements in order to analyse the entropic or enthalpic contributions to the dissolution process. Molecular dynamics simulations provided solvation free energies that were compared to experimental and structural information. Spatial distributions of solvent ions around the solutes when combined with IR measurements elucidate the structure of solvation environments. Interactions between the imidazolium rings of cations and the pi system of the solutes have been identified. However, ionic liquids with pyrrolidinium cations appeared as better solvents due to favourable enthalpic contributions compared to imidazolium cations. Long alkyl side chains on cations lead to higher solubility and lower enthalpy of dissolution by creating a "softer" solvation environment. Considering the effect of anions, small and planar anions lead to higher solubilities and lower enthalpies of dissolution of polyaromatic hydrocarbons. These findings provide the design principles based on molecular interactions and the structure of solvation environments to choose or formulate ionic liquids in view of their affinity for carbon nanomaterials. PMID- 28983550 TI - A combined experimental and theoretical approach towards mechanophenotyping of biological cells using a constricted microchannel. AB - We report a combined experimental and theoretical technique that enables the characterization of various mechanical properties of biological cells. The cells were infused into a microfluidic device that comprises multiple parallel micro constrictions to eliminate device clogging and facilitate characterization of cells of different sizes and types on a single device. The extension ratio lambda and transit velocity Uc of the cells were measured using high-speed and high resolution imaging which were then used in a theoretical model to predict the Young's modulus Ec = f(lambda, Uc) of the cells. The predicted Young's modulus Ec values for three different cell lines (182 +/- 34.74 Pa for MDA MB 231, 360 +/- 75 Pa for MCF 10A and, 763 +/- 93 Pa for HeLa) compare well with those reported in the literature from micropipette measurements and atomic force microscopy measurement within 10% and 15%, respectively. Also, the Young's modulus of MDA-MB 231 cells treated with 50 MUM 4-hyrdroxyacetophenone (for localization of myosin II) for 30 min was found out to be 260 +/- 52 Pa. The entry time te of cells into the micro-constrictions was predicted using the model and validated using experimentally measured data. The entry and transit behaviors of cells in the micro-constriction including cell deformation (extension ratio lambda) and velocity Uc were experimentally measured and used to predict various cell properties such as the Young's modulus, cytoplasmic viscosity and induced hydrodynamic resistance of different types of cells. The proposed combined experimental and theoretical approach leads to a new paradigm for mechanophenotyping of biological cells. PMID- 28983551 TI - Association of Enrollment in an Aerodigestive Clinic With Reduced Hospital Stay for Children With Special Health Care Needs. AB - Importance: Children with special health care needs (CSHCN) have disproportionate health care utilization. Previous studies have demonstrated that a primary medical home improves health care outcomes for this population. Objective: To elucidate if enrollment in a multidisciplinary aerodigestive clinic improves outcomes and reduces health care costs by decreasing admissions and inpatient days. Design, Setting, and Participants: A retrospective medical record review of 113 patients with aerodigestive disorders enrolled in a pediatric multidisciplinary clinic from June 2009 to December 2013 was performed. Of the 113 particpants, 58 (51.3%) were male, 59 (52.2%) had a tracheostomy, and 90 (80.5%) had a gastrostomy tube during their enrollment period. Patient ages at enrollment ranged from 0 to 20 years, with 59 (52.2%) ranging from 0 to 5 years, 23 (20.4%) ranging from 6 to 10 years, 18 (15.9%) ranging from 11 to 15 years, and 13 (11.5%) being 16 years or older. Admissions data before and after enrollment in a pediatric multidisciplinary clinic were examined. Main Outcomes and Measures: The main outcomes studied were changes in admissions and inpatient days before and after enrollment. Financial data were also examined to determine the reduction in technical direct cost. Results: The admissions data for 113 children were analyzed. No significant difference in number of admissions per year was seen with enrollment with a median difference of -0.30 admissions per year (range, -10.6 to 6.7 admissions per year; 95% CI, -3.5 to 2.9). However, there was a significant decrease seen in inpatient days per year following enrollment, with a median decrease of 4.1 inpatient days per year (range, -80 to 283.3 inpatient days per year; 95% CI, 0.33 to 91.0). When examining aerodigestive admissions alone, the median number of aerodigestive hospital days avoided per patient was 0.57 days per month, or 6.8 days per year, representing a 70% reduction in technical direct cost. Conclusions and Relevance: These findings indicate that for children with special health care needs, enrollment in a multidisciplinary aerodigestive clinic may improve health care outcomes by decreasing technical direct cost by 70% and significantly decreasing patient hospital days by an estimated 1 week per year. Furthermore, coordinated aerodigestive care in a medical home setting may lower health care expenditures from a systems-based perspective. PMID- 28983552 TI - Choriocapillaris Imaging Using Multiple En Face Optical Coherence Tomography Angiography Image Averaging. AB - Importance: Imaging of the choriocapillaris in vivo is challenging with existing technology. Optical coherence tomography angiography (OCTA), if optimized, could make the imaging less challenging. Objective: To investigate multiple en face image averaging on OCTA images of the choriocapillaris. Design, Setting, and Participants: Observational, cross-sectional case series at a referral institutional practice in Los Angeles, California. From the original cohort of 21 healthy individuals, 17 normal eyes of 17 participants were included in the study. The study dates were August to September 2016. Exposures: All participants underwent OCTA imaging of the macula covering a 3 * 3-mm area using OCTA software (Cirrus 5000 with AngioPlex; Carl Zeiss Meditec). One eye per participant was repeatedly imaged to obtain 9 OCTA cube scan sets. Registration was first performed using superficial capillary plexus images, and this transformation was then applied to the choriocapillaris images. The 9 registered choriocapillaris images were then averaged. Quantitative parameters were measured on binarized OCTA images and compared with the unaveraged OCTA images. Main Outcome and Measure: Vessel caliber measurement. Results: Seventeen eyes of 17 participants (mean [SD] age, 35.1 [6.0] years; 9 [53%] female; and 9 [53%] of white race/ethnicity) with sufficient image quality were included in this analysis. The single unaveraged images demonstrated a granular appearance, and the vascular pattern was difficult to discern. After averaging, en face choriocapillaris images showed a meshwork appearance. The mean (SD) diameter of the vessels was 22.8 (5.8) um (range, 9.6-40.2 um). Compared with the single unaveraged images, the averaged images showed more flow voids (1423 flow voids [95% CI, 967-1909] vs 1254 flow voids [95% CI, 825-1683], P < .001), smaller average size of the flow voids (911 [95% CI, 301-1521] um2 vs 1364 [95% CI, 645-2083] um2, P < .001), and greater vessel density (70.7% [95% CI, 61.9%-79.5%] vs 61.9% [95% CI, 56.0% 67.8%], P < .001). The distribution of the number vs sizes of the flow voids was skewed in both unaveraged and averaged images. A linear log-log plot of the distribution showed a more homogeneous distribution in the averaged images compared with the unaveraged images. Conclusions and Relevance: Multiple en face averaging can improve visualization of the choriocapillaris on OCTA images, transforming the images from a granular appearance to a level where the intervascular spaces can be resolved in healthy volunteers. PMID- 28983553 TI - Vaccination Challenges in Confronting the Resurgent Threat From Yellow Fever. PMID- 28983554 TI - Adopting the Results of Everest II Into Practice: A Clearer View From a Higher Level Study. PMID- 28983555 TI - Measuring Institutional Quality in Head and Neck Surgery Using Hospital-Level Data: Negative Margin Rates and Neck Dissection Yield. AB - Importance: Negative margins and lymph node yields (LNY) of 18 or more from neck dissections in patients with head and neck squamous cell carcinomas (HNSCC) have been associated with improved patient survival. It is unclear whether these metrics can be used to identify hospitals with improved outcomes. Objective: To determine whether 2 patient-level metrics would predict outcomes at the hospital level. Design, Setting, and Participants: A retrospective review of records from the National Cancer Database (NCDB) was used to identify patients who underwent primary surgery and concurrent neck dissection for HNSCC between 2004 and 2013. The percentage of patients at each hospital with negative margins on primary resection and an LNY 18 or more from a neck dissection was quantified. Cox proportional hazard models were used to define the association between hospital performance on these metrics and overall survival. Main Outcomes and Measures: Margin status and lymph node yield at hospital level. Overall survival (OS). Results: We identified 1008 hospitals in the NCDB where 64 738 patients met inclusion criteria. Of the 64 738 participants, 45 170 (69.8%) were men and 19 568 (30.2%) were women. The mean SD age of included patients was 60.5 (12.0) years. Patients treated at hospitals attaining the combined metric of a 90% or higher negative margin rate and 80% or more of cases with LNYs of 18 or more experienced a significant reduction in mortality (hazard ratio [HR] 0.93; 95% CI, 0.89-0.98). This benefit in survival was independent of the patient-level improvement associated with negative margins (HR, 0.73; 95% CI, 0.71-0.76) and LNY of 18 or more (HR, 0.85; 95% CI, 0.83-0.88). Including these metrics in the model neutralized the association of traditional measures of hospital quality (volume and teaching status). Conclusions and Relevance: Treatment at hospitals that attain a high rate of negative margins and LNY of 18 or more is associated with improved survival in patients undergoing surgery for HNSCC. These surgical outcome measures predicted outcomes independent of traditional, but generally nonmodifiable characteristics. Tracking of these metrics may help identify high quality centers and provide guidance for institution-level quality improvement. PMID- 28983556 TI - Efficacy and Safety of Ranibizumab With or Without Verteporfin Photodynamic Therapy for Polypoidal Choroidal Vasculopathy: A Randomized Clinical Trial. AB - Importance: Polypoidal choroidal vasculopathy (PCV) is a common subtype of exudative age-related macular degeneration among Asian individuals. To our knowledge, there are no large randomized clinical trials to evaluate intravitreal ranibizumab, with and without verteporfin photodynamic therapy (vPDT), for the treatment of PCV. Objective: To compare the efficacy and safety of combination therapy of ranibizumab and vPDT with ranibizumab monotherapy in PCV. Design, Setting, and Participants: A double-masked, multicenter randomized clinical trial of 322 Asian participants with symptomatic macular PCV confirmed by the Central Reading Center using indocyanine green angiography was conducted between August 7, 2013, and March 2, 2017. Interventions: Participants were randomized 1:1 to ranibizumab, 0.5 mg, and vPDT (n = 168; combination therapy group) or ranibizumab, 0.5 mg, and sham PDT (n = 154; monotherapy group). All participants received 3 consecutive monthly ranibizumab injections, followed by a pro re nata regimen. Participants also received vPDT/sham PDT on day 1, followed by a pro re nata regimen based on the presence of active polypoidal lesions. Main Outcomes and Measures: Step 1 assessed whether combination therapy was noninferior (5 letter margin) to monotherapy for change in best-corrected visual acuity from baseline and superior in complete polyp regression. If noninferiority was established, step 2 assessed whether combination therapy was superior to monotherapy measured by best-corrected visual acuity change at month 12. Results: Baseline demographics of the 322 participants were comparable between the treatment groups. Mean (SD) age of the patients was 68.1 (8.8) years, and overall, 69.9% of the patients were men. At baseline, the overall mean best corrected visual acuity and mean central subfield thickness were 61.1 letters and 413.3 MUm, respectively. At 12 months, mean improvement from baseline was 8.3 letters with combination therapy vs 5.1 letters with monotherapy (mean difference, 3.2 letters; 95% CI, 0.4-6.1), indicating that combination therapy met the predefined criterion for noninferiority as well as being superior to monotherapy (P = .01). Combination therapy was also superior to monotherapy in achieving complete polyp regression at month 12 (69.3% vs 34.7%; P < .001). Over 12 months, the combination therapy group received a median of 4.0 ranibizumab injections compared with 7.0 in the monotherapy group. Vitreous hemorrhage was the only ocular serious adverse event (combination therapy group, 1 [0.6%]; monotherapy group, 3 [2.0%]). Conclusions and Relevance: After 12 months, combination therapy of ranibizumab plus vPDT was not only noninferior but also superior to ranibizumab monotherapy in best-corrected visual acuity and superior in complete polyp regression while requiring fewer injections. Combination therapy should be considered for eyes with PCV. Trial Registration: clinicaltrials.gov Identifier: NCT01846273. PMID- 28983557 TI - Role of Deficient DNA Mismatch Repair Status in Patients With Stage III Colon Cancer Treated With FOLFOX Adjuvant Chemotherapy: A Pooled Analysis From 2 Randomized Clinical Trials. AB - Importance: The prognostic impact of DNA mismatch repair (MMR) status in stage III colon cancer patients receiving FOLFOX (folinic acid, fluorouracil, and oxaliplatin) adjuvant chemotherapy remains controversial. Objective: To determine the association of MMR status with disease-free survival (DFS) in patients with stage III colon cancer treated with FOLFOX. Design, Setting, and Participants: The evaluated biomarkers for MMR status were determined from prospectively collected tumor blocks from patients treated with FOLFOX in 2 open-label, phase 3 randomized clinical trials: NCCTG N0147 and PETACC8. The studies were conducted in general community practices, private practices, and institutional practices in the United States and Europe. All participants had stage III colon adenocarcinoma. They were enrolled in NCCTG N0147 from February 2004 to November 2009 and in PETACC8 from December 2005 to November 2009. Interventions: Patients in the clinical trials were randomly assigned to receive 6 months of chemotherapy with FOLFOX or FOLFOX plus cetuximab. Only those patients treated with FOLFOX alone were included in the present study. Main Outcomes and Measures: Association of MMR status with DFS was analyzed using a stratified Cox proportional hazards model. Multivariable models were adjusted for age, sex, tumor grade, pT/pN stage, tumor location, ECOG (Eastern Cooperative Oncology Group) performance status, and BRAF V600E mutational status. Results: Among 2636 patients with stage III colon cancer treated with FOLFOX, MMR status was available for 2501. Of these, 252 (10.1%) showed deficient MMR status (dMMR; 134 women, 118 men; median age, 59 years), while 2249 (89.9%) showed proficient MMR status (pMMR; 1020 women, 1229 men; median age, 59 years). The 3-year DFS rates in the dMMR and pMMR groups were 75.6% and 74.4%, respectively. By multivariate analysis, patients with dMMR phenotype had significantly longer DFS than those with pMMR (adjusted hazard ratio, 0.73; 95% CI, 0.54-0.97; P = .03). Conclusions and Relevance: The deficient MMR phenotype remains a favorable prognostic factor in patients with stage III colon cancer receiving FOLFOX adjuvant chemotherapy. Trial Registration: clinicaltrials.gov Identifier: NCT00079274 for the NCCTG N0147 trial and EudraCT identifier: 2005-003463-23 for the PETACC8 trial. PMID- 28983559 TI - Difficulties in Defining and Measuring Cancer-Related Fatigue. PMID- 28983558 TI - Association Between Opioid Prescribing Patterns and Abuse in Ophthalmology. AB - Importance: Drug overdoses have become the number 1 cause of mortality in American adults 50 years and younger. Prescription opioid abuse is a growing concern that has garnered widespread attention among policymakers and the general public. Objective: To determine the opioid prescribing patterns among ophthalmologists and elucidate their role in the prescription opioid abuse epidemic. Design, Setting, and Participants: In this observational cohort study, beneficiaries and their physicians were analyzed using 2013 to 2015 Medicare Part D Prescriber Data. The Centers for Medicare and Medicaid Services Medicare Part D Prescriber Public Use Files for 2013, 2014, and 2015 were accessed. Analysis began in June 2017. Data were collected and analyzed regarding the prescribing patterns for opioid drugs (eg, number of prescriptions written including refills, number of days' supply, and prescriber rates) for all participating ophthalmologists. Main Outcomes and Measures: The mean number of opioid prescriptions written annually by ophthalmologists; prescriber rates compared with all prescriptions written; and geographic distribution of opioid prescriptions written per ophthalmologist. Results: In 2013, 4167 of 19 615 ophthalmologists were women (21.2%). Consistently, most ophthalmologists (88% 89%) wrote 10 opioid prescriptions or fewer annually. Approximately 1% (0.94% 1.03%) of ophthalmologists wrote more than 100 prescriptions per year. On average, ophthalmologists wrote 7 opioid prescriptions per year (134 290 written annually by 19 638 physicians, on average) with a mean supply of 5 days. The 6 states with the highest volume of opioid prescriptions written annually per ophthalmologist were located in the southern United States. Conclusions and Relevance: In general, ophthalmologists show discretion in their opioid prescribing patterns. The present opioid abuse epidemic should prompt physicians to consider revisiting their prescribing protocols given the high risk for dependency. PMID- 28983560 TI - Combining Rhinoplasty With Upper Lip-Lift Using a Single Incision Line. PMID- 28983561 TI - Difficulties in Defining and Measuring Cancer-Related Fatigue-Reply. PMID- 28983563 TI - A Last Draw From the Boneyard. PMID- 28983562 TI - Adjuvant Ipilimumab for Melanoma-The $1.8 Million per Patient Regimen. PMID- 28983564 TI - Effect of Circulating Omentin-1 on the Retinal Circulation in Patients With Type 2 Diabetes Mellitus. AB - Purpose: To identify any significant correlations between retinal circulatory parameters and serum concentrations of omentin-1, a novel adipokine produced by adipocytes, in patients suffering from type 2 diabetes mellitus. Methods: Eighty seven patients suffering from type 2 diabetes and incipient diabetic retinopathy (DR) were analyzed and further divided into two groups according to sex. We compared the patients' retinal circulatory parameters measured with laser Doppler velocimetry and serum omentin-1 concentrations. Results: The plasma omentin-1 concentrations were related positively to the retinal blood flow (RBF) (r = 0.212; P = 0.048) and primarily with female sex (r = 0.288; P = 0.06) and negatively to the retinal arterial vascular resistance (RVR) (r = -0.218; P = 0.043). Moreover, the plasma omentin-1 concentration was modestly but not significantly positively related to the blood velocity. Multiple regression analysis showed that the serum omentin-1 level contributed independently and negatively to the RVR. Conclusions: Increased concentrations of plasma omentin-1 might be linked to elevated RBF levels probably through elevated blood velocity in patients suffering from type 2 diabetes with incipient DR, especially in female patients, which warrants further investigation. PMID- 28983567 TI - A Possible Association Between Hearing Loss and Zika Virus Infections. PMID- 28983568 TI - Ischemic Retinal Vascular Disease in an Infant With Hemophagocytic Lymphohistiocytosis. PMID- 28983569 TI - Retina Folds and Subretinal Fluid After Bell Palsy. PMID- 28983565 TI - The Burden of Primary Liver Cancer and Underlying Etiologies From 1990 to 2015 at the Global, Regional, and National Level: Results From the Global Burden of Disease Study 2015. PMID- 28983570 TI - Updating of visual orientation in a gravity-based reference frame. AB - The brain can use multiple reference frames to code line orientation, including head-, object-, and gravity-centered references. If these frames change orientation, their representations must be updated to keep register with actual line orientation. We tested this internal updating during head rotation in roll, exploiting the rod-and-frame effect: The illusory tilt of a vertical line surrounded by a tilted visual frame. If line orientation is stored relative to gravity, these distortions should also affect the updating process. Alternatively, if coding is head- or frame-centered, updating errors should be related to the changes in their orientation. Ten subjects were instructed to memorize the orientation of a briefly flashed line, surrounded by a tilted visual frame, then rotate their head, and subsequently judge the orientation of a second line relative to the memorized first while the frame was upright. Results showed that updating errors were mostly related to the amount of subjective distortion of gravity at both the initial and final head orientation, rather than to the amount of intervening head rotation. In some subjects, a smaller part of the updating error was also related to the change of visual frame orientation. We conclude that the brain relies primarily on a gravity-based reference to remember line orientation during head roll. PMID- 28983571 TI - A parametric texture model based on deep convolutional features closely matches texture appearance for humans. AB - Our visual environment is full of texture-"stuff" like cloth, bark, or gravel as distinct from "things" like dresses, trees, or paths-and humans are adept at perceiving subtle variations in material properties. To investigate image features important for texture perception, we psychophysically compare a recent parametric model of texture appearance (convolutional neural network [CNN] model) that uses the features encoded by a deep CNN (VGG-19) with two other models: the venerable Portilla and Simoncelli model and an extension of the CNN model in which the power spectrum is additionally matched. Observers discriminated model generated textures from original natural textures in a spatial three-alternative oddity paradigm under two viewing conditions: when test patches were briefly presented to the near-periphery ("parafoveal") and when observers were able to make eye movements to all three patches ("inspection"). Under parafoveal viewing, observers were unable to discriminate 10 of 12 original images from CNN model images, and remarkably, the simpler Portilla and Simoncelli model performed slightly better than the CNN model (11 textures). Under foveal inspection, matching CNN features captured appearance substantially better than the Portilla and Simoncelli model (nine compared to four textures), and including the power spectrum improved appearance matching for two of the three remaining textures. None of the models we test here could produce indiscriminable images for one of the 12 textures under the inspection condition. While deep CNN (VGG-19) features can often be used to synthesize textures that humans cannot discriminate from natural textures, there is currently no uniformly best model for all textures and viewing conditions. PMID- 28983572 TI - Risk of Intraocular Bleeding and the New Anticoagulants: Not Such a Big Effect Reply. PMID- 28983573 TI - Risk of Intraocular Bleeding and the New Anticoagulants: Not Such a Big Effect. PMID- 28983574 TI - Unilateral Nasal Obstruction. PMID- 28983575 TI - Association of Anesthesia Duration With Complications After Microvascular Reconstruction of the Head and Neck. AB - Importance: Prolonged anesthesia and operative times have deleterious effects on surgical outcomes in a variety of procedures. However, data regarding the influence of anesthesia duration on microvascular reconstruction of the head and neck are lacking. Objective: To examine the association of anesthesia duration with complications after microvascular reconstruction of the head and neck. Design, Setting, and Participants: The American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database was used to collect data. In total, 630 patients who underwent head and neck microvascular reconstruction were recorded in the NSQIP registry from January 1, 2005, through December 31, 2013. Patients who underwent microvascular reconstructive surgery performed by otolaryngologists or plastic surgeons were included in this study. Data analysis was performed from October 15, 2015, to January 15, 2016. Exposures: Microvascular reconstructive surgery of the head and neck. Main Outcomes and Measures: Patients were stratified into 5 quintiles based on mean anesthesia duration and analyzed for patient characteristics and operative variables (mean [SD] anesthesia time: group 1, 358.1 [175.6] minutes; group 2, 563.2 [27.3] minutes; group 3, 648.9 [24.0] minutes; group 4, 736.5 [26.3] minutes; and group 5, 922.1 [128.1] minutes). Main outcomes include rates of postoperative medical and surgical complications and mortality. Results: A total of 630 patients undergoing head and neck free flap surgery had available data on anesthesia duration and were included (mean [SD] age, 61.6 [13.8] years; 436 [69.3%] male). Bivariate analysis revealed that increasing anesthesia duration was associated with increased 30-day complications overall (55 [43.7%] in group 1 vs 80 [63.5%] in group 5, P = .006), increased 30-day postoperative surgical complications overall (45 [35.7%] in group 1 vs 78 [61.9%] in group 5, P < .001), increased rates of postoperative transfusion (32 [25.4%] in group 1 vs 70 [55.6%] in group 5, P < .001), and increased rates of wound disruption (0 in group 1 vs 10 [7.9%] in group 5, P = .02). No specific medical complications and no overall medical complication rate (24 [19.0%] in group 1 vs 22 [17.5%] in group 5, P = .80) or mortality (1 [0.8%] in group 1 vs 1 [0.8%] in group 5, P = .75) were associated with increased anesthesia duration. On multivariate analysis accounting for demographics and significant preoperative factors including free flap type, overall complications (group 5: odds ratio [OR], 1.98; 95% CI, 1.10-3.58; P = .02), surgical complications (group 5: OR, 2.46; 95% CI, 1.35-4.46; P = .003), and postoperative transfusion (group 5: OR, 2.31; 95% CI, 1.27-4.20; P = .006) remained significantly associated with increased anesthesia duration; the association of wound disruption and increased anasthesia duration was nonsignificant (group 5: OR, 2.0; 95% CI, 0.75-5.31; P = .16). Conclusions and Relevance: Increasing anesthesia duration was associated with significantly increased rates of surgical complications, especially the requirement for postoperative transfusion. Rates of medical complications were not significantly altered, and overall mortality remained unaffected. Avoidance of excessive blood loss and prolonged anesthesia time should be the goal when performing head and neck free flap surgery. Level of Evidence: 3. PMID- 28983576 TI - Image Averaging, a Powerful Tool in Optical Coherence Tomography and Optical Coherence Tomography Angiography. PMID- 28983577 TI - Early experience with robot-assisted laparoscopic hepatobiliary and pancreatic surgery in Singapore: single-institution experience with 20 consecutive patients. AB - INTRODUCTION: Experience with robot-assisted laparoscopic (RAL) hepatobiliary and pancreatic (HPB) surgery remains limited worldwide. In this study, we report our early experience with RAL HPB surgery in Singapore. METHODS: A retrospective review of the first 20 consecutive patients who underwent RAL HPB surgery at a single institution over a 34-month period from February 2013 to November 2015 was conducted. The 20 cases were performed by three principal surgeons, of which 17 (85.0%) were performed by a single surgeon. RESULTS: The median age of patients was 56 (range 22-75) years and median tumour size was 4.0 (range 1.2-7.5) cm. The surgeries performed included left-sided pancreatectomies (n = 10), hepatectomies (n = 7), triple bypass with bile duct exploration for obstructing pancreatic head cancer with choledocholithiasis (n = 1), cholecystectomy for Mirizzi's syndrome (n = 1) and gastric resection for gastrointestinal stromal tumour (n = 1). The median operation time was 445 (range 80-825) minutes and median blood loss was 350 (range 0-1,200) mL. There was only 1 (5%) open conversion. There were 2 (10.0%) major morbidities (> Grade II on the Clavien-Dindo classification) and no 30-day/in-hospital mortalities. There was no reoperation for postoperative complications. The median postoperative stay was 5.5 (range 3-22) days. CONCLUSION: Our initial experience confirms the feasibility and safety of RAL HPB surgery. PMID- 28983578 TI - The Singapore Paediatric Triage Scale Validation Study. AB - INTRODUCTION: This study aimed to determine the usefulness and validity of the triaging scale used in our emergency department (ED) by analysing its association with surrogate clinical outcome measures of severity consisting of hospitalisation rate, intensive care unit (ICU) admission, length of ED stay, predictive value for admission and length of hospitalisation. METHODS: A retrospective observational study was conducted of the performance markers of the Singapore Paediatric Triage Scale (SPTS) to identify children who needed immediate and greater care. All children triaged and attended to at the paediatric ED at KK Women's and Children's Hospital, Singapore, from 1 January 2014 to 31 December 2014 were included. Data was retrieved from the Online Paediatric Emergency Care system, which is used for patients' care from initial triaging to final disposition. RESULTS: Among 172,933 ED attendances, acuity levels 1, 2 plus, 2 and 3 were seen in 2.3%, 26.4%, 13.5% and 57.8% of patients, respectively. For admissions, triage acuity level 1 had a strong positive predictive value (79.5%), while triage acuity level 3 had a strong negative predictive value (93.7%). Fewer patients with triage acuity level 3 (6.3%) were admitted as compared to those with triage acuity level 1 (79.5%) (p < 0.001). There was a correlation between triage level and length of ED stay. CONCLUSION: The SPTS is a valid tool for use in the paediatric emergency setting. This was supported by strong performance in important patient outcomes, such as admission to hospital, ICU admissions and length of ED stay. PMID- 28983579 TI - Cost-effectiveness of two-dose human papillomavirus vaccination in Singapore. AB - INTRODUCTION: Cervical cancer is the tenth most common cancer and the eighth most frequent cause of death among women in Singapore. As human papillomavirus (HPV) infection is the necessary cause of cervical cancer, the risk of cervical cancer can be substantially reduced through vaccination. This study was conducted to evaluate the cost-effectiveness of two-dose HPV vaccination as part of a national vaccination programme for 12-year-old girls in Singapore, from the perspective of the healthcare payer. METHODS: A lifetime Markov cohort model was used to evaluate the cost-effectiveness of introducing the AS04-adjuvanted HPV-16/18 vaccine (AS04-HPV-16/18v) to the current cervical screening programme in Singapore. Furthermore, the cost-effectiveness of the AS04-HPV-16/18v was compared with the HPV-6/11/16/18 vaccine (4vHPV). Model inputs were derived from local data, where possible, and validated by clinical experts in Singapore. RESULTS: Introduction of the AS04-HPV-16/18v in Singapore was shown to prevent 137 cervical cancer cases and 48 cervical cancer deaths when compared with screening alone. This resulted in an incremental cost-effectiveness ratio of SGD 12,645 per quality-adjusted life year (QALY) gained, which is cost-effective according to the World Health Organization threshold for Singapore. When discounted at 3%, AS04-HPV-16/18v was dominant over 4vHPV, with cost savings of SGD 80,559 and 28 additional QALYs gained. In the one-way sensitivity analysis, AS04-HPV-16/18v remained cost-effective compared with screening alone and dominant compared with 4vHPV. CONCLUSION: AS04-HPV-16/18v is the most cost effective choice for reducing the burden of cervical cancer through universal mass vaccination for 12-year-old girls in Singapore. PMID- 28983580 TI - Laparoscopic sleeve gastrectomy for morbidly obese adolescents in Singapore. AB - INTRODUCTION: Laparoscopic sleeve gastrectomy (LSG) outcomes among adolescents and factors associated with adolescent obesity in Singapore were evaluated. METHODS: Prospectively collected data of patients aged 16-19 years who underwent LSG was retrospectively reviewed. A lifestyle questionnaire, Berlin and Epworth scores, and Patient Health Questionnaire-9 scores were collected. Preoperative anthropometrics, comorbidities, weight loss and body composition outcomes were recorded. RESULTS: Among 208 LSGs, 13 (6.3%) were performed on obese adolescents. Mean age and body mass index (BMI) at first presentation were 19.1 +/- 0.9 (range 16.8-19.8) years and 46.2 +/- 6.3 (range 36-57) kg/m2, respectively. There was family history of obesity (n = 7) and regular consumption of high-calorie drinks (n = 12). Most patients had comorbidities (n = 12), including hypertension (n = 5), asthma (n = 4), diabetes mellitus (n = 3), hernia (n = 3) and obstructive sleep apnoea requiring continuous positive airway pressure support (n = 3). At one year, excess weight loss was 64.3% +/- 34.7% (range 21.8%-101.5%), while BMI and fat mass dropped to 31.2 +/- 7.6 (range 23-40) kg/m2 and 17.4 kg, respectively. Pain score was 2/10 at 24 hours after surgery. Mean postoperative stay was 2.7 days. No complications or readmissions occurred. Remission of diabetes mellitus and hypertension was reported in two of three and four of five adolescents, respectively, within one year of surgery. CONCLUSION: LSG is a safe option for adolescents with good short-term weight loss outcomes and remission of metabolic comorbid conditions. PMID- 28983581 TI - Bioinformatics analysis of fibroblasts exposed to TGF-beta at the early proliferation phase of wound repair. AB - The aim of the current study was to identify gene signatures during the early proliferation stage of wound repair and the effect of TGF-beta on fibroblasts and reveal their potential mechanisms. The gene expression profiles of GSE79621 and GSE27165 were obtained from GEO database. Differentially expressed genes (DEGs) were identified using Morpheus and co-expressed DEGs were selected using Venn Diagram. Gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) online tool. Protein protein interaction (PPI) networks of the DEGs were constructed using Cytoscape software. PPI interaction network was divided into subnetworks using the MCODE algorithm and the function of the top one module was analyzed using DAVID. The results revealed that upregulated DEGs were significantly enriched in biological process, including the Arp2/3 complex-mediated actin nucleation, positive regulation of hyaluronan cable assembly, purine nucleobase biosynthetic process, de novo inosine monophosphate biosynthetic process, positive regulation of epithelial cell proliferation, whereas the downregulated DEGs were enriched in the regulation of blood pressure, negative regulation of cell proliferation, ossification, negative regulation of gene expression and type I interferon signaling pathway. KEGG pathway analysis showed that the upregulated DEGs were enriched in shigellosis, pathogenic Escherichia coli infection, the mitogen activated protein kinase signaling pathway, Ras signaling pathway and bacterial invasion of epithelial cells. The downregulated DEGs were enriched in systemic lupus erythematosus, lysosome, arachidonic acid metabolism, thyroid cancer and allograft rejection. The top 10 hub genes were identified from the PPI network. The top module analysis revealed that the included genes were involved in ion channel, neuroactive ligand-receptor interaction pathway, purine metabolism and intestinal immune network for IgA production pathway. The functional analysis revealed that TGF-beta may promote fibroblast migration and proliferation and defend against microorganisms at the early proliferation stage of wound repair. Furthermore, these results may provide references for chronic wound repair. PMID- 28983582 TI - Effects of Tripterygium glycoside treatment on experimental autoimmune encephalomyelitis. AB - Experimental autoimmune encephalomyelitis (EAE) is an autoimmune disease mediated by CD4+ T cells. It is characterized by mononuclear cell infiltration around the small blood vessels in the central nervous system (CNS). Previous investigations have found that apoptosis is associated with the occurrence and development of autoimmune disease, and that mononuclear cell apoptosis and clearance from the CNS is one of the repair mechanisms of EAE. Tripterygium wilfordii glycoside (TWP) is an organic matter isolated from Tripterygium wilfordii, which has anti inflammatory and immunosuppressive effects. In the present study, male Lewis rats were randomly divided into a normal control, EAE and TWP groups. Rats in EAE and TWP groups received injections of emulsified EAE antigen (myelin protein) at two points on the footpad while control group received PBS. The TWP group was then treated with TWP daily for 21 days. Symptoms and nerve function scores were observed and evaluated. Specimens of blood, brain and spinal cord were collected for further pathological examination, Tunel assay, ELISA and immunohistochemistry were performed to examine the effect of TWP on the onset of EAE, and changes in CNS inflammatory infiltration, cell apoptosis, and the expression of nuclear factor (NF)-kappaB P65 and interleukin (IL)-2. The results showed that the TWP treatment group exhibited decreased EAE and delayed onset, compared with the control. The clinical symptoms were significantly reduced and alleviation of inflammatory cell infiltration was observed. Compared with the EAE group, a higher inflammatory cell apoptotic rate, and reduced serum levels of IL-2 and NF kappaB p65-positive cells were observed in the TWP treatment group. Therefore, TWP effectively inhibited EAE via the inhibition of CNS inflammatory cell infiltration, enhancement of inflammatory cell apoptosis, and downregulation of the expression of NF-kappaB and IL-2. PMID- 28983583 TI - Aberrant production of soluble inducible T cell co-stimulator and soluble programmed cell death protein 1 in patients with chronic hepatitis B. AB - Previous studies demonstrated that immune dysregulation is an important cause of hepatitis B virus (HBV)-mediated liver damage. Co-stimulators including programmed cell death protein 1 (PD-1) and inducible T cell co-stimulator (ICOS) are involved in the pathogenesis of HBV. In the present study, the serum levels of soluble (s)PD-1 and sICOS in patients with chronic HBV infections, were investigated, and the association between sPD-1 and sICOS levels and liver injury degree was investigated. Serum sPD-1 and sICOS levels were increased in the HBV patient group particularly in the HBV external core antigen positive group. In the immune clearance group, sPD-1 and sICOS were increased compared with the tolerance group. Furthermore, the relative mRNA expression levels were also increased in patients with HBV. However there was no correlation between sPD-1 and sICOS levels and HBV antibodies or PD-1/ICOS mRNA copies. The altered sPD-1 and sICOS serum levels in the different HBV groups may reflect the dysregulation of T cell activation, and may be associated with the HBV pathological process. PMID- 28983584 TI - Na+/K+-ATPase DR region-specific antibody protects U251 cells against hypoxia reperfusion-induced injury via the PI3K/AKT and ERK pathways. AB - Cerebral ischemia is a condition in which there is insufficient blood flow to the brain to meet metabolic demand. This leads to poor oxygen supply or cerebral hypoxia and to the death of brain tissue or cerebral infarction/ischemic stroke. In the present study, an Na+/K+-ATPase (NKA) DR region-specific antibody (DRSAb) was established and purified and it was demonstrated that DRSAb induced a protective effect on human astrocytes (U251) via the phosphoinositide 3-kinase (PI3K)/AKT and extracellular signal-regulated protein kinase (ERK) signaling pathways. The binding of DRSAb on NKA was revealed using flow cytometry. High signals were detected on U251 cells incubated with DRSAb, but not with control sera or BSA. The viability of the hypoxia/reperfusion (H/R)-treated cells was markedly increased by DRSAb administration of 0.3-0.5 uM. The optimal concentration of DRSAb was 0.4 uM for attenuation of the injury induced by H/R. The administration of 0.4 uM DRSAb markedly reduced the number of apoptotic cells compared with control sera. The application of PD98059, an ERK inhibitor, and LY 294002, an AKT inhibitor, attenuated the protective effect induced by DRSAb in the U251 cells subjected to H/R. Furthermore, the application of LY294002 prior to incubation with DRSAb eliminated the activation of ERK1/2, whereas the use of PD98059 failed to attenuate the effect of DRSAb on PI3K/AKT activation. These results indicated that the protective effects of DRSAb against H/R injury in U251 cells occurred via stimulation of the PI3K/AKT and ERK signaling pathways. PMID- 28983585 TI - Complex role of connexin 43 in astrocytic tumors and possible promotion of glioma associated epileptic discharge (Review). AB - Connexin (Cx)43 is a multifunction protein which forms gap junction channels and hemi-channels. It also contains abundant binding domains which possess the ability to interact with certain Cx43-associated proteins and therefore serve a fundamental role in various physiological and pathological functions. However, the understanding of the association between cancer and Cx43 along with Cx43-gap junctions (GJ) remains unclear. All available data illustrate that Cx43 and its associated GJ serve important functions in cancers. The expression levels of Cx43 demonstrate a downward trend and an increase in the levels of malignancy, particularly in astrocytomas. The GJ intercellular communication activity in glioma cells can be adjusted via Cx43 phosphorylation and through the combination of Cx43 and its associated protein. Available evidence reveals Cx43 as a tumor inhibiting factor that suppresses glioma growth and proliferation. However, its mechanism is also regarded as complicated and ambiguous. Furthermore, it is apparent that Cx43-GJ and the carboxyl tail may contribute to glioma growth and proliferation too. However, this valuable role could be weakened by its effects on migration and invasiveness. The detailed mechanism remains unclear and full of controversies. Cx43 can enhance the motor ability and invasiveness of astrocytic glioma cells. It is also able to influence glioma cells to detach from the tumor core to the peritumoral neocortex. This peritumoral region has recently been regarded as the basic focus of glioma-associated seizure. Thus, Cx43 may take part in the onset and development of glioma-associated epileptic discharge. In addition, change and increase of Cx43 expression in GJs has been observed in seizure perilesional tissue, which is associated with brain tumors. Cx43 or GJ/hemi-channels exert enduring effects in the promotion of glioma-associated epileptic release through direct mass effects and change of the tumor microenvironment. However, there are still a number of issues concerning this aspect that require further exploration. Cx43, as a potential treatment target against this incurable disease and its common symptom of epilepsy, requires further investigation. PMID- 28983586 TI - Directed transdifferentiation of Muller glial cells to photoreceptors using the sonic hedgehog signaling pathway agonist purmorphamine. AB - Specification of distinct cell types from Muller glial cells is key to the potential application of endogenous repair in retinal regeneration. Sonic hedgehog (SHH) has been established as a potent mitogen for rat Muller glial cells, which also induces Muller glial cells to dedifferentiate and adopt the phenotype of rod photoreceptors. The present study investigated the effects of purmorphamine, a small molecule that activates the SHH-pathway, in the proliferation, dedifferentiation and transdifferentiation of Muller glial cells, as determined by several methods including immunofluorescence, polymerase chain reaction and western blotting. It was demonstrated that it may be able to replace SHH for the regeneration of retinal neurons. Purmorphamine was revealed to stimulate the proliferation of Muller glial cells by increasing the expression of cyclin D1 and cyclin D3. In addition, purmorphamine-treated Muller glial cells were induced to dedifferentiate by inducing the expression of progenitor-specific markers; subsequently differentiating into rod-like photoreceptors. Intraocular injection of purmorphamine promoted the activation of Muller glial cells, and in turn, the production of rod-like photoreceptors in acute damaged retina. These results suggested that the endogenous neurogenic capacity of retinal Muller glial cells may be enhanced by this small molecular agonist of the SHH signaling pathway. PMID- 28983587 TI - Bmi-1-targeting suppresses osteosarcoma aggressiveness through the NF-kappaB signaling pathway. AB - Bone cancer is one of the most lethal malignancies and the specific causes of tumor initiation are not well understood. B-cell-specific Moloney murine leukemia virus integration site 1 protein (Bmi-1) has been reported to be associated with the initiation and progression of osteosarcoma, and as a prognostic indicator in the clinic. In the current study, a full-length antibody targeting Bmi-1 (AbBmi 1) was produced and the preclinical value of Bmi-1-targeted therapy was evaluated in bone carcinoma cells and tumor xenograft mice. The results indicated that the Bmi-1 expression level was markedly upregulated in bone cancer cell lines, and inhibition of Bmi-1 by AbBmi-1 reduced the invasiveness and migration of osteosarcoma cells. Overexpression of Bmi-1 promoted proliferation and angiogenesis, and increased apoptosis resistance induced by cisplatin via the nuclear factor-kappaB (NF-kappaB) signal pathway. In addition, AbBmi-1 treatment inhibited the tumorigenicity of osteosarcoma cells in vivo. Furthermore, AbBmi-1 blocked NF-kappaB signaling and reduced MMP-9 expression. Furthermore, Bmi-1 promoted osteosarcoma tumor growth, whereas AbBmi-1 significantly inhibited osteosarcoma tumor growth in vitro and in vivo. Notably, AbBmi-1 decreased the percentages of Ki67-positive cells and terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells in tumors compared with Bmi-1-treated and PBS controls. Notably, MMP-9 and NF-kappaB expression were downregulated by treatment with AbBmi-1 in MG-63 osteosarcoma cells. In conclusion, the data provides evidence that AbBmi-1 inhibited the progression of osteosarcoma, suggesting that AbBmi-1 may be a novel anti-cancer agent through the inhibition of Bmi-1 via activating the NF-kappaB pathway in osteosarcoma. PMID- 28983588 TI - Dipterocarpus obtusifolius attenuates the effects of lipopolysaccharide-induced inflammatory response in RAW264.7 macrophages. AB - Dipterocarpus obtusifolius has been traditionally used as a herbal medicine and is considered to have anticancer properties. The biological activity of D. obtusifolius in inflammation and the underlying mechanisms of its activity remain to be elucidated. The present study investigated the effects of D. obtusifolius methanolic extract (DOME) on lipopolysaccharide (LPS)-stimulated inflammation in RAW264.7 cells. The effects of DOME on the production of nitric oxide, prostaglandin E2 and pro-inflammatory cytokines were assessed by ELISA, western blot analysis and reverse transcription-quantitative polymerase chain reaction. It was demonstrated that expression of inducible nitric oxide synthase, cyclooxygenase-2, interleukin-1beta and tumor necrosis factor-alpha was suppressed by DOME in LPS-stimulated cells. Furthermore, treatment with DOME suppressed phosphorylation of mitogen activated protein kinase (MAPK) molecules, including extracellular signal-regulated kinase, c-Jun N-terminal kinase and p38 MAPK. Translocation of the nuclear factor-kappaB p65 subunit into the nucleus was additionally inhibited by DOME. Phosphorylation of MAPK promoter activity was inhibited by treatment with DOME, PD98059, SB202190 and SP600125. These results demonstrated that DOME inhibits LPS-induced inflammatory responses. Therefore, DOME may be a potential therapeutic approach for the treatment of inflammatory diseases. PMID- 28983589 TI - Honokiol triggers receptor-interacting protein kinase 3-mediated cell death of neuroblastoma cells by upregulating reactive oxygen species. AB - Neuroblastoma is the most common form of childhood extracranial tumor and almost half of neuroblastoma cases occur in infants under two years old. Neuroblastoma accounts for ~6-10% of childhood cancers and 15% of cancer-associated childhood mortality. However, an effective treatment remains to be developed. Honokiol exhibits long-lasting central muscle relaxation, anti-inflammatory, antibacterial, antimicrobial, antiulcer, antioxidation, antiaging and antitumor effects. Honokiol has been previously demonstrated to kill neuroblastoma cells, however, the underlying mechanism of action remains unclear. The present study reports that honokiol inhibits the growth of neuroblastoma cells via upregulation of reactive oxygen species (ROS). MTT assays demonstrated that treatment of Neuro 2a neuroblastoma cells with honokiol resulted in time- and dose-dependent inhibition of cell proliferation, which was associated with upregulation of the protein expression of receptor-interacting protein kinase 3 (RIP3), as demonstrated by western blot analysis. Furthermore, knockdown of RIP3 by small interfering RNA, or pharmacological inhibition of RIP3 by the RIP3 specific inhibitor necrosulfonamide, reversed honokiol-induced loss of cell viability in Neuro-2a cells. Importantly, honokiol significantly increased the intracellular ROS levels as determined by a 2',7'-dichlorofluorescin diacetate assay, while ROS scavenger N-acetyl cysteine significantly prevented the induction of ROS and RIP3 by honokiol. The results of the present study indicate that honokiol may suppress the growth of neuroblastoma Neuro-2a cells, at least partially, through ROS mediated upregulation of RIP3. PMID- 28983590 TI - I-BET151 inhibits osteoclastogenesis via the RANKL signaling pathway in RAW264.7 macrophages. AB - Excessive bone resorption mediated by osteoclasts may lead to the risk of various lytic bone diseases. In the present study, the effects of I-BET151, a bromodomain and extra terminal domain protein inhibitor, on osteoclastogenesis in RAW264.7 cells and the underlying mechanism of this process was investigated. Cells were divided into 6 groups, including the control group, receptor activator of nuclear factor-kappaB ligand (RANKL) group and 4 other groups containing RANKL and I BET151 at different concentrations. Tartrate-resistant acid phosphatase (TRACP) staining was used to observe the effect of I-BET151 on osteoclastogenesis and the number of TRACP positive multinucleated cells was calculated. Western blotting was used to evaluate the expression of tumor necrosis factor receptor associated factor (TRAF6), nuclear factor of activated T-cells cytoplasmic 1 (NFATcl), transcription factor p65 (p65), nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-alpha (IkappaB-alpha), extracellular signal regulated kinase, Jun N-terminal kinase (JNK) and p38. mRNA expression levels of osteoclast specific genes TRACP, matrix metalloproteinase-9 (MMP9), cathepsin K (CtsK) and proto-oncogene tyrosine-protein kinase Src (c-Src) were measured using the reverse transcription-quantitative polymerase chain reaction (RT-qPCR). TRACP staining results demonstrated that I-BET151 inhibited osteoclastogenesis induced by RANKL and the inhibition was dose dependent. TRACP multinucleated positive cells were significantly decreased when treated with I-BET151 compared with the RANKL group. The inhibitory effect on TRAF6 was significant when concentrations of 100 and 200 nM I-BET151 were used, and NFATcl was significantly inhibited when a concentration of 200 nM was used compared with the RANKL group, in a dose dependent manner. Nuclear translocation of p65 was significantly inhibited by I BET151 at all concentrations. The degradation of IkappaB-alpha, and phosphorylation of JNK and p38 were also significantly inhibited by I-BET151, with the exception of the expression of IkappaB-alpha following treatment with 50 nM I-BET151. The RT-qPCR results revealed that osteoclast-specific genes TRACP, MMP9, CtsK and c-Src were all dose-dependently inhibited by I-BET151, except for CtsK. In conclusion, I-BET151 may significantly suppress the osteoclastogenesis of RAW264.7 cells via the RANKL signaling pathway. PMID- 28983591 TI - Chondromodulin-I suppresses tumorigenesis of human osteosarcoma cells. AB - Osteosarcoma is the most common type of bone cancer, and accounts for ~3% of cancers that occurring in children. Chondromodulin-I (ChM-I) is a 25 kDa glycoprotein that is expressed mainly in cartilage. ChM-I demonstrates anti angiogenic activity and has been suggested to inhibit endothelial cells from invading cartilage, and then has been shown to be an inhibitor of tumorigenesis. However, it remains unclear if ChM-I has any direct anti-tumorigenesis role on osteosarcoma. Therefore, the present study aimed to identify whether ChM-I has any direct inhibit effect on human osteosarcoma cells. A bromodeoxyuridine incorporation assay was performed on the Saos-2 human osteosarcoma cell line treated with or without recombinant human ChM-I, to evaluate its impact on DNA synthesis. An adenovirus carrier for the expression of ChM-I was constructed and transfected into tumor cells in vitro to evaluate the effect of ChM-I on tumor cells. Additionally, ChM-I was knocked down by using small interfering RNA to downregulate the expression of ChM-I. Cell invasion, migration and cell-colony formation assays, and xenograft tumor experiments were performed to evaluate the effects of ChM-I on tumor cells in vitro and in vivo. The results demonstrated that ChM-I could suppress DNA synthesis of human osteosarcoma cells, and it also exerted an inhibitory effect on the proliferation and colony formation abilities of human osteosarcoma cells. In addition, ChM-I inhibited cell invasion and migration in vitro and suppressed osteosarcoma cell growth significantly in vivo. In conclusion, ChM-I directly suppressed the proliferation and growth of osteosarcoma cells in an anchorage-independent manner, and may therefore be a promising drug for the treatment of osteosarcoma. PMID- 28983592 TI - Amygdalin ameliorates the progression of atherosclerosis in LDL receptor deficient mice. AB - Previous studies have demonstrated that regulatory T cells (Tregs) are pivotal in the regulation of T cell-mediated immune responses in atherosclerosis, a chronic autoimmune-like disease. In the authors' previous studies, it was demonstrated that amygdalin ameliorated atherosclerosis by the regulation of Tregs in apolipoprotein E-deficient (ApoE-/-) mice. Therefore, the aim of the present study was to investigate the therapeutic effect of amygdalin on low-density lipoprotein (LDL) receptor deficient (LDLR-/-) mice, and to examine its immune regulatory function by the stimulation of Tregs. To establish an atherosclerosis mouse model, the LDLR-/- mice were fed a high fat and high cholesterol diet then the total plasma cholesterol, triglyceride, LDL and chemokines levels were measured by an ELISA. Following sacrificing the mice, the upper sections of the aorta were stained by hematoxylin and eosin, and Oil red O to assess the plaque area. Then western blotting and reverse transcription polymerase chain reactions were performed to analysis the expression levels of cluster of differentiation 68, monocyte chemoattractant protein-1, matrix metalloproteinase (MMP)-2, MMP-9 and forkhead box P3 (Foxp3). To further confirm the activation of FOXP3 by amygdalin, lentiviruses carrying Foxp3 shRNA were injected into the mice, and the serum cytokines levels were measured by ELISA. Following feeding of the mice with a high-fat/high-cholesterol diet, the LDLR-/- mice demonstrated comparatively higher levels of triglyceride, total cholesterol and LDL, compared with levels in the amygdalin-treated mice. By comparing the vessel area, lumen area, plaque area, and percentage aortic plaque coverage, the effects of amygdalin on pre existing lesions were assessed. In addition, the levels of CD68, monocyte chemoattractant protein-1, MMP-2 and MMP-9 were analyzed, and analysis of the expression of interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF)-alpha indicated that the mice treated with amygdalin had decreased expression of pro inflammatory cytokines. The mRNA and protein levels of Foxp3 were also quantified, and the mice treated with amygdalin demonstrated an increased number of Tregs. The knockdown of Foxp3mRNA resulted in the increased secretion of IL 1beta, IL-6 and TNF-alpha. Therefore, the data indicated that amygdalin regulated the formation of atherosclerosis and stabilized the plaque by suppressing inflammatory responses and promoting the immune-modulation function of Tregs. Taken together, the results demonstrated the therapeutic effect of amygdalin on atherosclerosis. PMID- 28983593 TI - Anti-osteoporotic effects of tetramethylpyrazine via promoting osteogenic differentiation and inhibiting osteoclast formation. AB - Long-term glucocorticoid therapy results in various side effects, including a high incidence of glucocorticoid-induced osteoporosis (GIOP), which is the most common form of secondary osteoporosis. Excess glucocorticoids reduce the viability of bone marrow-derived mesenchymal stem cells (BMSCs) and prolong osteoclast survival. These two types of cell are essential in the balance between bone formation and resorption. Tetramethylpyrazine (TMP), the pharmacologically active component extracted from Chuanxiong, has been reported to protect BMSCs from glucocorticoid-induced apoptosis. In the present study, the protective effects of TMP on BMSC differentiation and osteoclasts maturation in GIOP were investigated in vivo and in vitro. The immunostaining of osterix (OSX) and tartrate-resistant acid phosphatase (TRAP) staining indicated that TMP promoted osteogenesis and inhibited osteoclastogenesis in a rat model of GIOP. Treatment with 10-6 M dexamethasone (Dex) significantly inhibited BMSC differentiation and increased TRAP-positive cells in vitro. However, different concentrations of TMP (50, 100 and 200 uM) ameliorated the negative effects of Dex by promoting the activity of alkaline phosphatase (ALP) and the calcium mineralization of BMSCs following osteogenic induction, which increased the expression levels of osteogenic genes, including ALP, collagen type I alpha1, osteocalcin and OSX, and decreased osteoclastogenesis-related genes, including TRAP, nuclear factor of T cells cytoplasmic 1 and cathepsin K. In addition, it was found that the inhibition of receptor activator of nuclear factor-kappaB ligand and intereleukin 6 in BMSCs may be a possible mechanism for the protective effects of TMP against glucocorticoid-induced osteoclastogenesis. These results are the first, to the best of our knowledge, to demonstrate that TMP promotes BMSC differentiation and inhibits osteoclastogenesis to ameliorate bone mass change in GIOP. PMID- 28983594 TI - MicroRNA-24-1-5p promotes malignant melanoma cell autophagy and apoptosis via regulating ubiquitin D. AB - The present study aimed to investigate the key roles and possible regulatory mechanism of microRNA (miR)-24-1-5p in regulating the autophagy, and apoptosis of malignant melanoma cells. The expression levels of miR-24-1-5p in malignant melanoma tissues were determined. Human melanoma A375 cells were transfected with miR-24-1-5p mimic and control. The effects of miR-24-1-5p overexpression on regulating the expressions of autophagy-related proteins [microtubule-associated protein 1A/1B-light chain 3 (LC3)-II, LC3-I and Beclin-1] and apoptosis-related proteins [apoptosis regulator Bcl-2 (Bcl-2) and (BCL2 like 1) Bcl-xL] were investigated. The percentage of apoptotic cells in different transfected cells was detected. In addition, luciferase reporter assays were performed to confirm whether ubiquitin D (UBD) was a target of miR-24-1-5p. The effects of UBD silencing on autophagy and apoptosis were also investigated. The expression levels of janus kinase (JNK), phosphorylated (P)-JNK, Jun proto-oncogene AP-1 transcription factor subunit (c-Jun) and p-c-Jun were determined following the overexpression of miR-24-1-5p, and UBD. In comparison with adjacent normal tissues, miR-24-1-5p was significantly downregulated in malignant melanoma tissues. Overexpression of miR-24-1-5p significantly increased the levels of LC3 II/I ratio and Beclin-1 expression, and decreased the expression levels of Bcl-2 and Bcl-xL. Flow cytometry also showed that miR-24-1-5p overexpression promoted cell apoptosis. Moreover, UBD was confirmed as a direct target of miR-24-1-5p. Silencing of UBD promoted melanoma cell autophagy and apoptosis via regulating the expression levels of related proteins. Besides, the levels of the p-JNK/JNK and p-c-Jun/Jun ratios were significantly increased following miR-24-1-5p overexpression, which were reversed following co-overexpression of miR-24-1-5p, and UBD. Overexpression of miR-24-1-5p may target UBD, and subsequently promote the autophagy and apoptosis of malignant melanoma cells through activation of the JNK signaling pathway. PMID- 28983595 TI - Bufalin induced apoptosis in SCC-4 human tongue cancer cells by decreasing Bcl-2 and increasing Bax expression via the mitochondria-dependent pathway. AB - The aim of the present study was to investigate the cytotoxic effects of bufalin on SCC-4 human tongue cancer cells. Cell morphological changes and viability were examined using phase contrast microscopy and flow cytometry, respectively. The results indicated that bufalin induced morphological changes and reduced total viable cells. Apoptotic cell death was analyzed by DAPI staining and DNA gel electrophoresis; the results revealed that bufalin induced cell apoptosis. Levels of reactive oxygen species (ROS), Ca2+, nitric oxide (NO) and mitochondrial membrane potential (DeltaPsim) were measured by flow cytometry, and bufalin was observed to increase Ca2+ and NO production, decrease the DeltaPsim and reduce ROS production in SCC-4 cells. In addition, western blotting was performed to detect apoptosis-associated protein expression. The results demonstrated that bufalin reduced the expression of the anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) and increased the expression of the pro-apoptotic protein, Bcl-2 associated X protein. However, bufalin treatment also increased the expression of other apoptosis-associated proteins such as apoptosis-inducing factor and endonuclease G in SCC-4 cells. Based on these findings, bufalin may induce apoptotic cell death via mitochondria-dependent pathways in human tongue cancer SCC-4 cells. PMID- 28983596 TI - CISD2 promotes the proliferation of glioma cells via suppressing beclin-1 mediated autophagy and is targeted by microRNA-449a. AB - CDGSH iron sulfur domain 2 (CISD2) has been found to be important in carcinogenesis. However, the role of CISD2 in glioma remains to be elucidated. The present study aimed to investigate the role of CISD2 in glioma using the reverse transcription-quantitative polymerase chain reaction, western blotting, co-immunoprecipitation assay, immunofluorescence staining and other methods. The results demonstrated that the mRNA and protein levels of CISD2 were found to be upregulated in glioma tissues, compared with the levels in matched normal tissues. Clinical data analysis showed that the level of CISD2 was negatively correlated with the survival rates of patients with glioma. In addition, high levels of CISD2 were associated with advanced clinical stage, relapse, vascular invasion and increased tumor size. The inhibition of CISD2 suppressed the proliferation and survival of glioma cells in vitro and in vivo. Mechanistically, it was found that small interfering RNA-induced knock down of CISD2 inhibited the proliferation of glioma cells through activating beclin-1-mediated autophagy. The results also revealed that CISD2 was a target of microRNA (miR)-449a. Together, the results of the present study demonstrated that CISD2 was increased in glioma samples and was associated with poor prognosis and aggressive tumor behavior. The miR-449a/CISD2/beclin-1-mediated autophagy regulatory network contributed to the proliferation of glioma cells. Targeting this pathway may be a promising strategy for glioma therapy. PMID- 28983597 TI - Mediating macrophage immunity with wogonin in mice with vascular inflammation. AB - Vascular inflammation may induce a number of diseases, including organ damage or failure, heart attack and stroke. The present study aimed to investigate the use of wogonin, a compound extracted from herbs, to mediate inflammatory reactions in vascular inflammation. Wogonin was loaded in a well-characterized polymeric biomaterial carrier. In mice with streptozotocin-induced vascular inflammation, wogonin treatment regulated the production of inflammatory cytokines, including interleukin-6, tumor necrosis factor-alpha and granulocyte macrophage colony stimulating factor. To understand the impact of wogonin on major immune cells, macrophages were treated with wogonin in vitro. It was determined that wogonin did not affect macrophage viability, and that wogonin regulated the relative ratio of M1 versus M2 macrophages. In addition, in co-culture, wogonin decreased inflammatory cytokine production and regulated the activation of macrophage surface markers including CD80, CD86 and CD40. Results from the present study may aid in our understanding of the effects of wogonin in regulating inflammation, especially its effects on macrophages. PMID- 28983599 TI - Baicalin potentiates TRAIL-induced apoptosis through p38 MAPK activation and intracellular reactive oxygen species production. AB - The combination of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) with other agents has been recognized as a promising strategy to overcome TRAIL resistance in cancer cells. Baicalin (5, 6-dihydroxy-7-o-glucuronide flavone) is a flavonoid from the root of the medicinal herb Scutellaria baicalensis Georgi, which has been reported to exert antioxidant, anti inflammatory, antiviral and anticancer activities in vitro. However, the effect of baicalin on TRAIL-induced cytotoxicity has not been previously reported. In the present study, the effect of combining TRAIL and baicalin was investigated in non-small cell lung cancer cell lines. The results revealed that baicalin was able to sensitize A549 and H2009 cells to TRAIL-induced apoptosis. This was detected by the potentiation of poly-adenosine-5'-diphosphate-ribose polymerase cleavage and Annexin V-fluorescein isothiocyanate staining of cells co-treated with baicalin and TRAIL. In addition, p38 mitogen-activated protein kinase was activated in baicalin and TRAIL co-treated cancer cells, whereas the p38 inhibitor SB203580 effectively suppressed cell death within the co-treated cells. Butylated hydroxyanisole and N-acetyl-cysteine, known reactive oxygen species (ROS) scavengers, significantly suppressed the potentiated cytotoxicity induced by baicalin and TRAIL co-treatment. The present study is the first, to the best of our knowledge, to demonstrate that baicalin enhances the anticancer activity of TRAIL via p38 activation and ROS accumulation, and may be exploited for anticancer therapy. PMID- 28983598 TI - PDGF signaling pathway in hepatic fibrosis pathogenesis and therapeutics (Review). AB - The platelet-derived growth factor (PDFG) signaling pathway exerts persistent activation in response to a variety of stimuli and facilitates the progression of hepatic fibrosis. Since this pathway modulates a broad spectrum of cellular processes, including cell growth, differentiation, inflammation and carcinogenesis, it has emerged as a therapeutic target for hepatic fibrosis and liver-associated disorders. The present review exhibits the current knowledge of the role of the PDGF signaling pathway and its pathological profiles in hepatic fibrosis, and assesses the potential of inhibitors which have been investigated in the experimental hepatic fibrosis model, in addition to the clinical challenges associated with these inhibitors. PMID- 28983600 TI - CD146+ skeletal stem cells from growth plate exhibit specific chondrogenic differentiation capacity in vitro. AB - Skeletal stem cells (SSCs) are a population of progenitor cells which give rise to postnatal skeletal tissues including bone, cartilage and bone marrow stroma, however not to adipose, haematopoietic or muscle tissue. Growth plate chondrocytes exhibit the ability of continuous proliferation and differentiation, which contributes to the continuous physiological growth. The growth plate has been hypothesized to contain SSCs which exhibit a desirable differentiation capacity to generate bone and cartilage. Due to the heterogeneity of the growth plate chondrocytes, SSCs in the growth plate are not well studied. The present study used cluster of differentiation (CD)146 and CD105 as markers to isolate purified SSCs. CD105+ SSCs and CD146+ SSCs were isolated using a magnetic activated cell sorting method. To quantitatively investigate the proliferation and differentiation ability, the colony-forming efficiency (CFE) and multi lineage differentiation capacity of CD105+ SSCs and CD146+ SSCs were compared with unsorted cells and adipose-derived stem cells (ASCs). It was revealed that CD105+ and CD146+ subpopulations represented subsets of SSCs which generated chondrocytes and osteocytes, however not adipocytes. Compared with CD105+ subpopulations and ASCs, the CD146+ subpopulation exhibited a greater CFE and continuous high chondrogenic differentiation capacity in vitro. Therefore, the present study suggested that the CD146+ subpopulation represented a chondrolineage-restricted subpopulation of SSCs and may therefore act as a valuable cell source for cartilage regeneration. PMID- 28983601 TI - PKCzeta, MMP-2 and MMP-9 expression in lung adenocarcinoma and association with a metastatic phenotype. AB - The aim of the present study was to investigate protein kinase C zeta type (PKCzeta), matrix metalloproteinase (MMP)-2 and MMP-9 expression in lung adenocarcinoma and to define their association with in vitro invasion and metastatic capacity. PKCzeta, MMP-2 and MMP-9 expression was assessed by immunohistochemistry in 110 cases of lung adenocarcinoma. PKCzeta small interfering (si)RNA was transfected into A549 cells, and western blotting was used to confirm PKCzeta-knockdown in transfected cells and to measure MMP-2 and MMP-9 levels. A Transwell invasion assay was used to detect in vitro invasive capacity. The rates of positive PKCzeta, MMP-2 and MMP-9 staining in lung adenocarcinoma tissues were 52.73, 55.45 and 61.82%, respectively. PKCzeta expression was increased in malignant tissues compared with adjacent normal lung tissues and was associated with lymph node metastasis (P<0.05), although it was not associated with any other clinicopathological parameters, including sex, age, tumor size, smoking status or distant metastases (all P>0.05). PKCzeta, MMP-2 and MMP-9 expression was markedly decreased in siPKCzeta-treated A549 cells, which exhibited a significantly decreased invasive capacity in the Transwell invasion assay (P<0.05). In conclusion, PKCzeta promoted lung adenocarcinoma invasion and metastasis, and its expression was associated with MMP-2 and MMP-9 expression. PKCzeta may be a potential target for gene therapy in lung adenocarcinoma. PMID- 28983602 TI - The role of TGFbeta-HGF-Smad4 axis in regulating the proliferation of mouse airway progenitor cells. AB - The interaction between airway epithelial progenitor cells and their microenvironment is critical for maintaining lung homeostasis. This microenvironment includes fibroblast cells, which support the growth of airway progenitor cells. However, the mechanism of this support is not fully understood. In the present study, the authors observed that inhibition of transforming growth factor (TGF)-beta signal with SB431542 promotes the expression of hepatocyte growth factor (HGF) in fibroblast cells. The HGF receptor, c-Met, is expressed on airway progenitor cells; HGF promotes the colony-forming ability of airway progenitor cells. The deletion of Smad4 in airway progenitor cells increases the colony-forming ability, suggesting that Smad4 plays a negative role in the regulating the proliferation of airway progenitor cells. These data demonstrated that the regulation of airway progenitor cells by TGF-beta depends on TGF betaR1/2 on stromal cells, rather than on epithelial progenitor cells. These data suggested a role for the TGF-beta-TGF-betaR1/2-HGF-Smad4 axis in airway epithelial homeostasis and sheds new light on the interaction between airway progenitor cells and their microenvironment. PMID- 28983603 TI - Inflammatory and oxidative stress-associated factors in chronic intermittent hypoxia in Chinese patients, rats, lymphocytes and endotheliocytes. AB - In order to investigate the association between inflammatory and oxidative stress (OS)-associated factors in chronic intermittent hypoxia (CIH), 238 CIH patients and 156 healthy volunteers were included. CIH rat and lymphocytes were used as experimental models. Interleukin (IL)-6, tumor necrosis factor-alpha (TNF-alpha), C-reactive protein (CRP), nitric oxide (NO) and nitric oxide synthase (NOS) were analyzed. Patients with CIH were older, with hypertension, increased heart rate (HR) and body mass index (BMI), and there were more males than females. Those with a history of smoking or type 2 diabetes (T2DM) history exhibited an increased risk of CIH. Serum IL-6, TNF-alpha and CRP in patients with CIH were increased, while NO and NOS were decreased. Hakka patients exhibited increased BMI measurements and NO expression, and decreased systolic arterial pressure, IL 6 and TNF-alpha compared with non-Hakka patients. Rats with CIH exhibited hypertension and stable weight, less activity and decreased appetite, increased HR and serum IL-6, TNF-alpha and CRP, and decreased NO and NOS. IL-6, TNF-alpha, CRP, NO and induced-NOS (iNOS) were increased in the lymphocytes of CIH rats compared with healthy ones. In rat endotheliocytes induced by CIH, IL-6, TNF alpha, CRP and iNOS increased, while NO and endothelial-NOS (eNOS) decreased. In the supernatant of co-cultured lymphocytes and endotheliocytes, IL-6, TNF-alpha and CRP increased, although NO and NOS decreased. In conclusion, age, male gender, BMI, smoking and T2DM history, serum IL-6, TNF-alpha and CRP were positively correlated with CIH combined with hypertension, while NO and NOS were negatively correlated with CIH. Serum NO was predominantly synthesized and released by eNOS. Hakka patients exhibited decreased inflammation and OS with CIH. Increasing IL-6, TNF-alpha and CRP, and decreasing NO and NOS are biomarkers of CIH, which could be targets in diagnosis, treatment and prevention of CIH. PMID- 28983604 TI - Sanggenon C protects against cardiomyocyte hypoxia injury by increasing autophagy. AB - Sanggenon C is isolated from Morus alba, a plant that has been used for anti inflammatory purposes in Oriental medicine. Little is known about the effect of Sanggenon C on cardiomyocyte hypoxia injury. This study, using H9c2 rat cardiomyoblasts, was designed to determine the effects of Sanggenon C on cardiomyocyte hypoxia injury. Inflammatory cytokine levels were measured by reverse transcription-polymerase chain reaction, reactive oxygen species were measured by 2',7'-dichlorofluorescin diacetate fluorescent probe, autophagy was detected using the LC3II/I ratio and cell apoptosis was detected by TUNEL staining. The molecular mechanisms underlying Sanggenon C-induced cyto-protection were also determined by western blotting, especially the possible involvement of autophagy and AMP-activated protein kinase (AMPK). Results indicated that samples pretreated with different concentrations of Sanggenon C (1, 10 and 100 uM) reduced the expression levels of pro-inflammatory cytokines, including tumor necrosis factor alpha, interleukin (IL)-1 and IL-6, under hypoxia. The beneficial effects of Sanggenon C were also associated with reduced levels of reactive oxygen species generation and increased levels of antioxidant nitric oxide and superoxide dismutase. Sanggenon C enhanced hypoxia-induced autophagy as evidenced by the increased expression levels of autophagy-associated proteins Beclin and autophagy related 5 as well as the decreased the accumulation of p62, and increased the LC3II/I ratio. Sanggenon C also reduced hypoxia-induced apoptosis as detected by TUNEL staining and the expression of Bcl-2 proteins. The beneficial effects of Sanggenon C were associated with enhanced activation level of AMPKalpha and suppressed hypoxia-induced mechanistic target of rapamycin (mTOR) and forkhead box O3a (FOXO3a) phosphorylation. The AMPK inhibitor Compound C (CpC) was used, and the anti-apoptotic and pro-autophagy effects of Sanggenon C in response to hypoxia were abolished by CpC. In conclusion, the current study demonstrated that Sanggenon C possessed direct cytoprotective effects against hypoxia injury in cardiac cells via signaling mechanisms involving the activation of AMPK and concomitant inhibition of mTOR and FOXO3a. PMID- 28983605 TI - LDHA promotes tumor metastasis by facilitating epithelial-mesenchymal transition in renal cell carcinoma. AB - Previous studies have indicated that high expression of lactate dehydrogenase A (LDHA) exists in many human cancers. Recently, several reports showed that silencing or inhibition of LDHA could suppress metastasis of human cancer including renal cell carcinoma (RCC). However, the mechanism remains unknown. The role of LDHA in RCC migration and invasion was investigated using immunohistochemistry, western blotting, Transwell and scratch assays, and in vivo experiment. The influence of LDHA on the Warburg effect was also investigated by LDHA activity and lactate production assay. LDHA was overexpressed in RCC tissues and predicted a worse survival following renal resection. Correlation analysis demonstrated that LDHA was negatively correlated with E-cadherin and positively with N-cadherin. Experimentally, both in vivo and in vitro experiments found downregulation of LDHA suppressed RCC cells migration and invasion by inhibiting EMT. In addition, results indicated LDHA could promote the Warburg effect. Further research presented that the LDHA inhibitor, oxamate, suppressed tumor metastasis by inhibiting LDHA activity and EMT. These results demonstrated that LDHA mediates tumor metastasis by promoting EMT in RCC, suggesting that LDHA could be a promising therapeutic target for RCC therapy. PMID- 28983606 TI - PARP-1 may be involved in hydroquinone-induced apoptosis by poly ADP-ribosylation of ZO-2. AB - Hydroquinone (HQ), a major reactive metabolite of benzene, contributes to benzene induced leukemia. The molecular mechanisms that underlie this activity remain to be elucidated. Poly ADP-ribosylation (PARylation) is a type of reversible posttranslational modification that is performed by enzymes in the PAR polymerase (PARP) family and mediates different biological processes, including apoptosis. Zona occludens 2 (ZO-2) is a tight junction scaffold protein, which is involved in cell proliferation and apoptosis. The present study investigated the activity and mechanisms regulated by PARP-1 during HQ-induced apoptosis using TK6 lymphoblastoid cells and PARP-1-silenced TK6 cells. The results revealed that exposure to 10 uM HQ for 72 h induced apoptosis in TK6 cells and that apoptosis was attenuated in PARP-1-silenced TK6 cells. In cells treated with HQ, inhibition of PARP-1 increased the expression of B cell leukemia/lymphoma 2 (Bcl-2), increased ATP production and reduced reactive oxygen species (ROS) production relative to the levels observed in cells treated with HQ alone. Co-localization of ZO-2 and PAR (or PARP-1 protein) was determined using immunofluorescence confocal microscopy. The findings of the present study revealed that ZO-2 was PARylated via an interaction with PARP-1, which was consistent with an analysis of protein expression that was performed using western blot analysis, which determined that ZO-2 protein expression was upregulated in HQ-treated control cells and downregulated in HQ-treated PARP-1-silenced TK6 cells. These findings indicated that prolonged exposure to a low dose of HQ induced TK6 cells to undergo apoptosis, whereas inhibiting PARP-1 attenuates cellular apoptosis by activating Bcl-2 and energy-saving processes and reducing ROS. The present study determined that PARP-1 was involved in HQ-induced apoptosis by PARylation of ZO 2. PMID- 28983608 TI - Alterations in cyclin D1 and cyclin-dependent kinase 4 expression in the amygdalae of post-traumatic stress disorder rats. AB - The amygdalae are an important component of the human limbic system and exhibit a key role in emotional and behavioral reactions. Previous studies have demonstrated abnormal function and morphology in the amygdalae of post-traumatic stress disorder (PTSD)-like animal models, however the underlying molecular mechanisms remain elusive. The authors have previously demonstrated that PTSD induced increased apoptosis in the amygdala of PTSD-like animals. Cyclin D1 and cyclin-dependent kinase 4 (CDK4) are two important regulators of the cell cycle. The study explored the expression of cyclin D1 and CDK4 in the amygdala in PTSD. The single-prolonged stress (SPS) rat model was used as a PTSD-like model. Ultrastructural alterations of cells in the amygdala were observed using transmission electron microscopy (TEM). 4',6-Diamidino-2-phenylindole (DAPI) fluorescence was employed to detect nuclear pycnosis. Cyclin D1 and CDK4 expression in the amygdala cells was examined using immunofluorescence, Western blotting and reverse transcription-quantitative polymerase chain reaction. TEM revealed morphological alterations to the amygdala cells of the SPS rats. DAPI stained nuclear brightness levels differed between the control and SPS groups. Expression of cyclin D1 and CDK4 in the amygdala increased gradually 1 day and 4 days following SPS stimulation, and peaked 7 days following SPS stimulation at the protein and mRNA levels, in comparison with the control rats. These findings suggest that SPS resulted in increased cyclin D1 and CDK4 expression, which may accelerate cell apoptosis. This may be associated with SPS-induced abnormal function and structure of the amygdala. PMID- 28983607 TI - Iguratimod prevents ovariectomy-induced bone loss and suppresses osteoclastogenesis via inhibition of peroxisome proliferator-activated receptor gamma. AB - Iguratimod is known for its anti-inflammatory activities and therapeutic effects in patients with rheumatoid arthritis. It has previously been demonstrated that iguratimod attenuates bone destruction and osteoclast formation in the Walker 256 rat mammary gland carcinoma cell-induced bone cancer pain model. Therefore, it was hypothesized that iguratimod may additionally exhibit therapeutic effects on benign osteoclast-associated diseases including postmenopausal osteoporosis. In the present study, ovariectomized mice were used to investigate the effects of iguratimod in vivo. Bone marrow mononuclear cells were cultured to detect the effects of iguratimod on receptor activator of nuclear factor-kappaB ligand (RANKL)-induced osteoclastogenesis in vitro and the molecular mechanisms involved. It was demonstrated that iguratimod may prevent ovariectomy-induced bone loss by suppressing osteoclast activity in vivo. Consistently, iguratimod may inhibit RANKL-induced osteoclastogenesis and bone resorption in primary bone marrow mononuclear cells. At the molecular level, peroxisome proliferator activated receptor-gamma (PPAR-gamma)/c-Fos pathway, which is essential in RANKL induced osteoclast differentiation, was suppressed by iguratimod. Subsequently, iguratimod decreased the expression of nuclear factor of activated T cells c1 and downstream osteoclast marker genes. The results of the present study demonstrated that iguratimod may inhibit ovariectomy-induced bone loss and osteoclastogenesis by modulating RANKL signaling. Therefore, iguratimod may act as a novel therapeutic to prevent postmenopausal osteoporosis. PMID- 28983609 TI - Molecular mechanisms of the inhibitory effects of jiangu granule-containing serum on RANKL-induced osteoclastogenesis. AB - Postmenopausal osteoporosis (PMOP) is characterized by increased bone loss due to enhanced osteoclastogenesis and bone resorption. A Chinese herbal formula, jiangugranule (JG), exhibited great efficacy in the clinical treatment of PMOP. However, the molecular mechanisms underlying the therapeutic effects remain unclear. The present study aimed to examine the effects of JG-containing serum on receptor activator of nuclear factor-kappaB (NF-kappaB) ligand (RANKL)-induced osteoclastogenesis. Osteoclast precursor RAW264.7 cells were cultured and treated with JG-containing serum in the presence of RANKL. Following 6 days of culture, the cells were stained with tartrate-resistant acid phosphatase and the rate of differentiation was calculated. In addition, cells were treated with JG containing serum for 24, 48 and 96 h and total RNA and proteins were extracted for reverse transcription-quantitative polymerase chain reaction and western blot analysis to detect mRNA and protein expression, respectively, of key molecules in the RANK/RANKL signaling pathway, including RANK, tumor necrosis factor receptor associated factor 6, NF-kappaB (p50 and p52 subunits), c-Fos and nuclear factor of activated T cells, cytoplasmic 1 (NFATc1). The results revealed that JG containing serum inhibited RANKL-induced osteoclastogenesis and reduced mRNA and protein expression of RANK, c-Fos and NFATc1. The results suggested that JG may regulate osteoclast differentiation through the RANK/RANKL signaling pathway, which may be a possible mechanism for the therapeutic effects of JG on PMOP. PMID- 28983610 TI - Network centrality in patients with acute unilateral open globe injury: A voxel wise degree centrality study. AB - The present study aimed to investigate functional networks underlying brain activity alterations in patients with acute unilateral open globe injury (OGI) and associations with their clinical features using the voxel-wise degree centrality (DC) method. In total, 18 patients with acute OGI (16 males and 2 females), and 18 healthy subjects (16 males and 2 females), closely matched in age, sex and education, participated in the present study. Each subject underwent a resting-state functional magnetic resonance imaging scan. The DC method was used to assess local features of spontaneous brain activity. Receiver operating characteristic curve analysis was used to distinguish OGIs from healthy controls (HCs). Correlation analysis was used to examine the association between the observed mean DC values of different brain areas and behavioral performance. Compared with HCs, patients with acute unilateral OGI had significantly increased DC values in the bilateral primary visual cortex (V1/V2) and left precuneus (PCUN), and significantly decreased DC values in the right insula, left insula, right inferior parietal lobule (IPL)/supramarginal gyrus (SMG), IPL/SMG, right supplementary motor area and right postcentral gyrus. Additionally, in the acute OGI group, it was observed that the duration of OGI was negatively correlated with the DC signal value of the bilateral V1/V2 (r=-0.581; P=0.011) and left PCUN (r=-0.508; P=0.031). Acute OGI led to brain functional network dysfunction in a number of brain regions, which may indicate impairment of the visual cortex and other vision-associated brain regions in OGI. PMID- 28983611 TI - Suppression by HSP90 inhibitors of BMP-4-stimulated osteoprotegerin synthesis in osteoblasts: Attenuation of p70 S6 kinase. AB - Heat shock protein 90 (HSP90) is an ATP-dependent ubiquitous molecular chaperon which is important in cell homeostasis. The authors previously demonstrated that bone morphogenetic protein (BMP)-4 stimulates osteoprotegerin (OPG) production in osteoblast-like MC3T3-E1 cells, and that p70 S6 kinase positively regulates the OPG synthesis by BMP-4. The present study investigated the involvement of HSP90 in the BMP-4-stimulated OPG synthesis and the mechanism in MC3T3-E1 cells. HSP90 inhibitors, 17-allylamino-17demethoxy-geldanamycin (17-AAG), 17-dimethylamino ethylamino-17-demethoxy-geldanamycin (17-DMAG) and geldanamycin significantly suppressed the BMP-4-stimulated OPG release. Geldanamycin markedly reduced the BMP-4-induced mRNA expression of OPG. 17-AAG and 17-DMAG significantly attenuated the phosphorylation of p70 S6 kinase induced by BMP-4 without affecting the BMP-4 induced phosphorylation of mothers against decapentaplegic homolog 1/5. The results suggest that HSP90 inhibitors suppress the BMP-4-stimulated OPG synthesis in osteoblasts, and that their suppressive effects are exerted through downregulating p70 S6 kinase. PMID- 28983612 TI - Screening and validation of serum protein biomarkers for early postmenopausal osteoporosis diagnosis. AB - Postmenopausal osteoporosis is one of the most prominent worldwide public health problems and the morbidity is increasing with the aging population. It has been demonstrated that early diagnosis and intervention delay the disease progression and improve the outcome. Therefore, searching for biomarkers that are able to identify postmenopausal women at high risk for developing osteoporosis is an effective way to improve the quality of life of patients, and alleviate social and economic burdens. In the present study, a protein array was used to identify potential biomarkers. The bone mineral densities of 10 rats were dynamically measured in an ovariectomized model by micro-computed tomography assessment, and the early stage of osteoporosis was defined. Through the protein array-based screening, the expression levels of six serum protein biomarkers in ovariectomized rats were observed to alter at the initiation stage of the postmenopausal osteoporosis. Fractalkine, tissue inhibitor of metalloproteinases 1 and monocyte chemotactic protein-1 were finally demonstrated to be increased in the serum of eight enrolled postmenopausal osteoporosis patients using ELISA assay and were correlated with the severity of progressive bone loss. These biomarkers may be explored as potential early biomarkers to readily evaluate and diagnose postmenopausal osteoporosis in the clinic. PMID- 28983613 TI - High-dose PMA with RANKL and MCSF induces THP-1 cell differentiation into human functional osteoclasts in vitro. AB - Osteoclasts are large multinuclear cells, which serve role in erosive bone disease. However, it is not possible to separate osteoclasts from cortical bone in order to culture the cells for further experiments. Therefore, a human osteoclast model is required to investigate the underlying mechanism of bone destruction. The most commonly-used osteoclast model is the RAW264.7 cell line, a murine mononuclear macrophage cell line; however, there exists no reliable osteoclast model using a human cell line. The aim of the present study was to establish a functional osteoclast model using the THP-1 cell line. Suspended THP 1 cells were stimulated for 2 days with 5 or 100 ng/ml phorbol-12 myristate-13 acetate (PMA) in order to induce the cells to differentiate into adherent macrophages. A 10-day stimulation with 50 ng/ml receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (MCSF) was performed in order to induce macrophage differentiation into osteoclasts. Treatment with high-dose PMA with RANKL and MCSF enabled the THP-1 cells to form tartrate-resistant acid phosphatase-positive osteoclasts, which were able absorb bone in a bone resorption test. Treatment with low-dose PMA with RANKL and MCSF failed to induce THP-1 cell differentiation into osteoclasts. PMA alone, or a combination of RANKL and MCSF alone, is insufficient to stimulate THP-1 cell differentiation into osteoclasts. In the present study, a reliable human osteoclast model was established using the THP-1 cell line. This osteoclast model may provide a useful tool for further studies. PMID- 28983614 TI - Interaction network of coexpressed mRNA, miRNA, and lncRNA activated by TGF-beta1 regulates EMT in human pulmonary epithelial cell. AB - Noncoding RNAs (ncRNAs), such as microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), play increasingly important roles in pathological processes involved in disease development. However, whether mRNAs interact with miRNAs and lncRNAs to form an interacting regulatory network in diseases remains unknown. In this study, the interaction of coexpressed mRNAs, miRNAs and lncRNAs during tumor growth factor-beta1-activated (TGF-beta1) epithelial-mesenchymal transition (EMT) was systematically analyzed in human alveolar epithelial cells. For EMT regulation, 24 mRNAs, 11 miRNAs and 33 lncRNAs were coexpressed, and interacted with one another. The interaction among coexpressed mRNAs, miRNAs and lncRNAs were further analyzed, and the results showed the lack of competing endogenous RNAs (ceRNAs) among them. The mutual regulation may be correlated with other modes, such as histone modification and transcription factor recruitment. However, the possibility of ceRNA existence cannot be ignored because of the generally low abundance of lncRNAs and frequent promiscuity of protein-RNA interactions. Thus, conclusions need further experimental identification and validation. In this context, disrupting many altered disease pathways remains one of the challenges in obtaining effective pathway-based therapy. The reason being that one specific mRNA, miRNA or lncRNA may target multiple genes that are potentially implicated in a disease. Nevertheless, the results of the present study provide basic mechanistic information, possible biomarkers and novel treatment strategies for diseases, particularly pulmonary tumor and fibrosis. PMID- 28983615 TI - Identification of differentially expressed genes in Budd-Chiari syndrome by RNA sequencing. AB - Budd-Chiari syndrome (BCS) is an uncommon disease characterized by the occlusion or obstruction of hepatic venous outflow. The mechanism of BCS is still unclear and there are no accurate and effective diagnostic or therapeutic tools. In the present study, blood samples from BCS patients and healthy controls were used for RNA-sequencing. The differentially expressed genes (DEGs) in BCS patients compared with healthy controls were identified. Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes pathway analysis and Protein Protein Interaction (PPI) networks construction were performed for DEGs. A total of 405 DEGs including 317 upregulated and 88 downregulated DEGs were identified. The cytosol was the most significantly enriched GO term and the proteasome was also identified as significant enriched pathway. According to the PPI network of 30 DEGs (18 upregulated and 12 downregulated DEGs), synuclein alpha, tubulin beta 2A class IIa and zinc finger protein Gfi-1b (GFIIB) were the three most significant hub proteins. In conclusion, several DEGs including secreted protein acidic and cysteine rich, lipocalin-2, GFI1B and proteasome-associated DEGs may be associated with the pathological process of BCS. These results can provide novel clues for the pathogenesis and provide novel diagnostic and therapeutic strategies for BCS. PMID- 28983616 TI - Abnormal expression levels of BMP15/Smad1 are associated with granulosa cell apoptosis in patients with polycystic ovary syndrome. AB - Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects reproductive dysfunction and metabolism in women of childbearing age. An increasing number of studies have suggested that the bone morphogenetic protein 15 (BMP15) signalling pathway serves an important role in the pathogenesis of PCOS; however, the full mechanism remains unknown. The present study revealed that intrinsic follicular dysplasia may be associated with regulation disorders of ovarian granulosa cell apoptosis. Compared with the control group, body mass index, luteinising hormone and testosterone levels were significantly increased (P<0.05). The percentage of S phase cells was significantly higher, cells in G2/M phase cells was significantly lower, and cells undergoing apoptosis was significantly higher in the PCOS group compared with the control group (P<0.05). The expression levels of B-cell lymphoma 2 was significantly decreased in granulosa cells of PCOS group, whereas the expression of caspase-3 was higher than the control group (P<0.05). The rate of apoptosis of granulosa cells was measured by a terminal deoxynucleotide transferase dUTP nick-end labelling assay. The relative mRNA expression levels of BMP receptor 2 and SMAD1 were significantly decreased in granulosa cells in the PCOS group compared with the control (P<0.05). In addition, the expression of BMP15 in follicular fluid and Smad1 in granulosa cells was significantly decreased in the PCOS group compared with the control (P<0.05). The data suggested that the BMP15/Smad1 signalling pathway may be involved in granulosa cell apoptosis, and may be a target for clinical treatment for PCOS. PMID- 28983617 TI - CREB1 and Smad3 mediate TGF-beta3-induced Smad7 expression in rat hepatic stellate cells. AB - Transforming growth factor (TGF)-beta3 has previously been reported to antagonize hepatic fibrosis in vivo and in vitro. The present study aimed to investigate the mechanism underlying the involvement of TGF-beta3 in hepatic fibrosis. Short hairpin (sh)RNA-cAMP-responsive element binding protein (CREB) 1 and small interfering (si)RNA-Smad3 were utilized to silence the expression of CREB1 and Smad3 in hepatic stellate cells (HSCs), whereas the vector pRSV-CREB1 was used to induce CREB1 overexpression in HSCs. Cells were treated with or without exogenous TGF-beta3 or TGF-beta1, and mRNA and protein expression levels were assessed using reverse transcription-quantitative polymerase chain reaction and western blot analysis. Untreated cells served as the control group. Exogenous TGF-beta3 increased Smad7 mRNA and protein expression levels in rat HSCs, and CREB1 and Smad3 appeared to be implicated in the mechanism of Smad7. CREB1 knockdown inhibited the TGF-beta3-induced upregulation of Smad7, whereas its overexpression potentiated the Smad7 upregulation in HSCs; conversely, CREB1 manipulations had no effect on Smad7 expression under basal conditions. In addition, TGF-beta3 induced Smad7 upregulation was blocked when the activity of p38, a kinase upstream of CREB1, was inhibited. Furthermore, silencing Smad3 resulted in decreased Smad7 expression under basal conditions and in TGF-beta3-stimulated cells. Notably, Smad7 expression appeared to also be induced by exogenous TGF beta1, independent of CREB1. The present study demonstrated that TGF-beta3 increased Smad7 expression in HSCs, whereas CREB1 and Smad3 appeared to participate in the mechanism of induction. Smad3 is the key regulator whereas CREB-1 acts as a co-regulator. These results suggested that this mechanism may underlie the antagonizing effects of TGF-beta3 on hepatic fibrosis. PMID- 28983618 TI - Simvastatin attenuated rat thoracic aorta remodeling by decreasing ROCK2-mediated CyPA secretion and CD147-ERK1/2-cyclin pathway. AB - Reactive oxygen species-induced cyclophilin A (CyPA) release from vascular smooth muscle cells (VSMCs) may be inhibited by simvastatin in vitro. The present study aimed to further examine the effect of simvastatin on serum CyPA levels and the basigin (CD147)-extracellular signal-regulated kinase (ERK) 1/2-cyclin pathway during thoracic aorta remodeling. The mechanisms through which simvastatin may inhibit CyPA secretion from VSMCs were further investigated. Serum CyPA levels and the expression kinetics of CyPA-associated signaling pathways were examined following simvastatin treatment in rat thoracic aortas during hypertension. Cell lysates were prepared from middle layer of thoracic aortas at 1, 4, 8 and 12 weeks subsequent to surgery. ELISA analysis revealed that serum CyPA levels were gradually increased with the progression of thoracic aorta remodeling. Western blotting demonstrated that the expression of CD147, phosphorylated-ERK1/2, cyclin D1, cyclin A, and cyclin E were increased with the progression of thoracic aorta remodeling. Simvastatin administration for 4, 8 and 12 weeks diminished all these changes, as observed in the hypertensive group. VSMCs from simvastatin-treated rats secreted a decreased amount of CyPA compared with VSMCs from hypertensive rats. In addition, pretreatment with geranylgeraniol partly reversed the inhibitory effect of simvastatin on LY83583-induced CyPA secretion in cultured VSMCs, whereas GGTI-298 and KD025 [a selective Rho-associated protein kinase 2 (ROCK2) inhibitor] mimicked the inhibitory effect of simvastatin. The present study demonstrated that simvastatin alleviated thoracic aorta remodeling by reducing CyPA secretion and expression of the CD147-ERK1/2-cyclin signaling pathway. In addition, the results of the present study demonstrated that the Rho ROCK2 pathway mediated CyPA secretion from VSMCs. PMID- 28983619 TI - Circular RNA expression profiles of peripheral blood mononuclear cells in rheumatoid arthritis patients, based on microarray chip technology. AB - Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic synovial inflammation and finally leads to variable degrees of bone and cartilage erosion. The diagnosis of RA is not an accurate indicator, but a series of scores and the mechanisms underlying it remain only partially understood. The present study explored whether circular RNAs (circRNAs) contribute to the RA pathophysiological mechanism. Total RNA from peripheral blood mononuclear cells of 10 RA patients and 10 healthy controls were extracted and circRNA expression profiling was followed by microarray analysis. In addition, circRNA interactions with microRNAs were performed and microRNA response elements were listed to identify differentially expressed binding site targets in RA. Reverse transcription-quantitative polymerase chain reaction amplification (RT-qPCR) was used to verify the differential expression of circRNAs. A total of 584 circRNAs were differentially expressed in RA patients vs. healthy controls, by circRNA microarray, including 255 circRNAs which were significantly upregulated and 329 downregulated among the RA samples. RT-qPCR validation demonstrated that the expression levels of hsa_circRNA_104194, hsa_circRNA_104593, hsa_circRNA_103334, hsa_circRNA_101407 and hsa_circRNA_102594 were consistent with the results from the microarray analysis. The current study presented differentially expressed circRNAs and their corresponding microRNA binding sites in RA. circRNAs may exhibit a role in the regulation of expression of symbol genes that influence the occurrence and development of RA. PMID- 28983620 TI - Implantation of bone mesenchymal stem cells overexpressing miRNA-705 mitigated ischemic brain injury. AB - Ischemic brain damage remains the major cause of death and disability worldwide. Bone mesenchymal stem cell (BMSC) transplantation has been identified to serve important roles in cerebral infarction due to its multi-directional differentiation and proliferative ability. However, the function of miR-705 combined with BMSCs on ischemic brain injury remains to be fully elucidated. In the present study, an ischemic brain injury mouse model was constructed, and the mice were injected with BMSCs infected by lentiviral particles expressing miR-705 (BMSCs-Ad-miR-705) to explore the mechanism by which BMSCs-Ad-miR-705 mitigates neurological deficits in ischemic brain damage. In the sham group, no significant neurological injury evaluated via neurological deficit scores was identified, the morphological structure of brain stained with HE was almost normal, and few apoptotic cells were detected by TUNEL assay. However, the PBS group exhibited significant brain damage (P<0.05). BMSCs-Ad (BMSCs infected with control lentiviral particles) and BMSCs-Ad-miR-705 markedly mitigated neurological injury, suppressed morphological damage and inhibited neuronal apoptosis, however promoted the mRNA levels of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) examined by reverse transcription-quantitative polymerase chain reaction and western blotting. Notably, BMSCs-Ad-miR-705 improved the outcome of BMSCs-Ad transplantation. These data indicated that BMSCs Ad-miR-705 promoted the secretion of VEGF and BDNF, suppressed neuronal apoptosis, and stimulated neuronal regeneration, in turn mitigating the impairment of ischemic brain damage. PMID- 28983621 TI - Direct binding of RNF8 to SUMO2/3 promotes cell survival following DNA damage. AB - Ring finger protein 8 (RNF8), an FHA/RING domain containing E3 ubiquitin ligase, is critical in supporting genome integrity by facilitating the assembly of multiple DNA repair proteins at DNA lesions following DNA damage. In the present study, a search for novel binding partners of RNF8 was performed using a yeast two-hybrid screening assay, and small ubiquitin-like modifier (SUMO)2/3 was identified as one of the major RNF8-binding candidates. GST pull-down and immunoprecipitation assays revealed that RNF8 bound directly and noncovalently to SUMO2/3, but not to SUMO1, and that the FHA domain of RNF8 was required for the binding to SUMO2/3. Furthermore, RNF8 co-localized with SUMO2/3 at sites of DNA lesions in response to ionizing radiation, as revealed by immunofluorescence assay. Survival assay indicated that the depletion of RNF8 and SUMO2/3 resulted in decreased cellular resistance to genotoxic stress. These data suggested that the binding of RNF8 to SUMO2/3 promoted the response to DNA damage. PMID- 28983622 TI - Novel insights into the effect of paroxetine administration in pilocarpine induced chronic epileptic rats. AB - The aim of the present study was to investigate the role of paroxetine intervention in epilepsy, and its association with the expression of serotonin transporter (SERT) and hippocampal apoptosis. Thirty adult male Sprague Dawley rats were divided into control vehicle (n=6) and epileptic (n=24) groups. Status epilepticus (SE) was induced via systemic injection of pilocarpine, and seizure activity was monitored via video electroencephalogram. The epileptic group was then randomly divided into two groups; Four weeks following SE induction, paroxetine (5 mg/kg/day; SE + paroxetine group) or normal saline (SE group) was intraperitoneally injected for 4 weeks. Brain tissue was collected to evaluate apoptosis via terminal deoxynucleotidyl transferase dUTP nick-end labeling. SERT, B-cell lymphoma-2 (Bcl-2) and brain derived neurotropic factor (BDNF) expression levels were evaluated by western blotting, and miR-16 expression was evaluated by reverse transcription-quantitative polymerase chain reaction. Paroxetine did not affect the mortality of the pilocarpine-induced chronic epileptic rats. Spontaneous recurrent seizures (SSRs) were observed 7-28 days following SE induction. The frequency and stage of the SSRs were reduced by paroxetine administration. Apoptotic cells were observed in the epileptic hippocampus. Following paroxetine intervention, the staining intensity and number of apoptotic cells were significantly decreased. Expression levels of BDNF and Bcl-2 were lower in the SE group compared with the vehicle group. The former was not altered by paroxetine injection; however, the latter was increased. In the SE group, SERT expression was not altered in the raphe nucleus but was decreased in the hippocampus. Following paroxetine administration, SERT expression was decreased in the raphe nucleus and increased in the hippocampus. In the SE group, miR-16 expression was decreased in the raphe nucleus and increased in the hippocampus. Following paroxetine administration, miR-16 expression was not altered in the raphe nucleus but was reduced in the hippocampus. In conclusion, the seizures and hippocampal apoptosis observed in chronic epileptic rats were alleviated by paroxetine treatment. This effect may be associated with the reduced Bcl-2 and BDNF expression and the modulation of SERT expression. The alterations in miR-16 expression may provide a potential explanation for the modulation of apoptosis; however, further research is required to determine the complete underlying molecular mechanism. PMID- 28983623 TI - MicroRNA-378b regulates alpha-1-type 1 collagen expression via sirtuin 6 interference. AB - Ultraviolet (UV) light mediates skin aging and induces destruction of the dermis by modulating the expression levels of extracellular matrix-associated genes, including collagen and matrix metalloproteinases. Sirtuin 6 (SIRT6), a member of the sirtuin family of proteins, regulates collagen metabolism and is an established anti-aging protein. However, the exact underlying mechanism by which SIRT6 expression is regulated in dermal fibroblasts during the aging process is unclear. The present study demonstrated that expression of microRNA-378b (miR 378b) is induced in UVB-exposed human dermal fibroblasts (HDFs), and this was inversely associated with the mRNA expression levels of alpha-1-type 1 collagen (COL1A1). In addition, knockdown of miR-378b enhanced the mRNA expression levels of COL1A1 in HDFs. A target analysis for miR-378b was performed, and the results revealed that SIRT6, a regulator of COL1A1, contains a target sequence for miR 378b in its 3'untranslated region. Notably, the present study demonstrated that an miR-378b mimic and inhibitor may directly regulate SIRT6 expression in HDFs. In conclusion, the present study suggested that miR-378b represses the mRNA expression levels of COL1A1 via interference with SIRT6 in HDFs, and may contribute to the underlying molecular mechanism by which UVB inhibits collagen I in dermal fibroblasts. PMID- 28983624 TI - Dual specificity phosphatase 1 has a protective role in osteoarthritis fibroblast like synoviocytes via inhibition of the MAPK signaling pathway. AB - Increasing evidence indicates the important role of inflammation in the pathogenesis and progression of osteoarthritis (OA). Dual specificity phosphatase 1 (DUSP1), a negative regulator of the mitogen-activated protein kinase (MAPK) signaling pathway, has anti-inflammatory properties. In the present study, the expression of DUSP1 was investigated in human OA fibroblast-like synoviocytes (FLSs), human normal FLSs and OA FLSs pretreated with dexamethasone at the mRNA and protein levels. Then, the activation of MAPK pathway proteins and the expression of matrix metalloproteinase-13 (MMP-13) and cyclooxygenase-2 (COX-2) were measured by western blot analysis in the three groups of cells. Dexamethasone induced the expression of DUSP1 and inhibited the activation of the MAPK pathway and reduced the expression of MMP-13 and COX-2 in OA FLSs. However, the role of DUSP1 remained unclear. To clarify this, the effects of overexpression of DUSP1 in OA FLSs were determined using a DUSP1-overexpressing lentivirus. The results demonstrated that overexpression of DUSP1 in OA FLSs inhibited the activation of the MAPK pathway and expression of OA-associated mediators. The findings of the present study indicate that DUSP1 has a protective role in OA FLSs and may be a potential target in the treatment of OA. PMID- 28983625 TI - Resveratrol inhibits proliferation and migration through SIRT1 mediated post translational modification of PI3K/AKT signaling in hepatocellular carcinoma cells. AB - Resveratrol (RES), a polyphenolic compound present in grapes and red wine, has potential anticancer properties. The present study aimed to examine the effects of resveratrol and its underlying mechanism on hepatocellular carcinoma (HCC) cell lines HepG2, Bel-7402 and SMMC-7721. It was demonstrated that resveratrol inhibited the viability and proliferation of HCC cells assessed by MTT and EdU assays. TUNEL assay revealed that resveratrol induced cell apoptosis by increasing HCC apoptosis rate from 3+/-0.78% to 16+/-1.12% with upregulation of B cell lymphoma (Bcl)-2 associated X, apoptosis regulator and cleaved-poly (ADP Ribose) polymerase 1 (PARP), and downregulation of Bcl-2, caspase-3, caspase-7 and PARP. As a sirtuin (SIRT) 1 activator, resveratrol elevated SIRT1 protein expression and its enzyme activity and decreased expression levels of phosphorylated (p)-phosphoinositide-3-kinase (PI3K), p-AKT Serine/Threonine Kinase 1 (AKT), and its downstream target p-Forkhead Box O3a in HepG2 cells. Furthermore, inhibition of SIRT1 enzymatic activity by EX527 resulted in increased phosphorylation levels of PI3K and AKT. This demonstrated that resveratrol inhibited the PI3K/AKT pathway by SIRT1 activation. In addition to inhibition of cancer cell migration, tumor suppressor gene DLC1 Rho GTPase activating protein level was upregulated and its phosphorylation was enhanced by AKT with resveratrol treatment. These findings suggested that resveratrol inhibits proliferation and migration through SIRT1 mediated post-translational modification of PI3K/AKT pathway in HCC cells. PMID- 28983626 TI - GRP78 positively regulates estrogen-stimulated cell growth mediated by ER-alpha36 in gastric cancer cells. AB - Estrogen receptor (ER)-alpha36, a novel isoform of ER, primarily mediates non classical estrogen signaling. It has been reported that ER-alpha36-mediated growth stimulating signals are involved in the malignancy of gastric tumor cells. However, the mechanism underlying the regulation of ER-alpha36 function in development of gastric cancer remains to be elucidated. The present study investigated the role of 78 kDa glucose-regulated protein (GRP78) in the regulation of ER-alpha36 expression and signaling during the growth of gastric tumor cells. It was demonstrated that GRP78 expression was detectable in gastric cancer tumor tissues, and was positively-correlated with tumor stage, lymphatic metastasis and ER-alpha36 expression (P<0.05). An increased growth rate, and increased expression of ER-alpha36 and the cell cycle regulator cyclin D1 was detected in cells with GRP78 overexpression (SGC-High78 cells). SGC-High78 cells are more sensitive to estrogen compared with SGC-Control cells. Therefore, the results of the present study demonstrated that GRP78 positively regulated ER alpha36 expression and signaling with cell growth in gastric cancer, which is involved in gastric carcinogenesis. PMID- 28983627 TI - Systematic module approach identifies altered genes and pathways in four types of ovarian cancer. AB - The present study aimed to identify altered genes and pathways associated with four histotypes of ovarian cancer, according to the systematic tracking of dysregulated modules of reweighted protein-protein interaction (PPI) networks. Firstly, the PPI network and gene expression data were initially integrated to infer and reweight normal ovarian and four types of ovarian cancer (endometrioid, serous, mucinous and clear cell carcinoma) PPI networks based on Spearman's correlation coefficient. Secondly, modules in the PPI network were mined using a clique-merging algorithm and the differential modules were identified through maximum weight bipartite matching. Finally, the gene compositions in the altered modules were analyzed, and pathway functional enrichment analyses for disrupted module genes were performed. In five conditional-specific networks, universal alterations in gene correlations were revealed, which leads to the differential correlation density among disrupted module pairs. The analyses revealed 28, 133, 139 and 33 altered modules in endometrioid, serous, mucinous and clear cell carcinoma, respectively. Gene composition analyses of the disrupted modules revealed five common genes (mitogen-activated protein kinase 1, phosphoinositide 3-kinase-encoding catalytic 110-KDalpha, AKT serine/threonine kinase 1, cyclin D1 and tumor protein P53) across the four subtypes of ovarian cancer. In addition, pathway enrichment analysis confirmed one common pathway (pathways in cancer), in the four histotypes. This systematic module approach successfully identified altered genes and pathways in the four types of ovarian cancer. The extensive differences of gene correlations result in dysfunctional modules, and the coordinated disruption of these modules contributes to the development and progression of ovarian cancer. PMID- 28983628 TI - Long intergenic noncoding RNA p21 mediates oxidized LDL-induced apoptosis and expression of LOX-1 in human coronary artery endothelial cells. AB - Atherosclerosis is the most common pathological cause of cardiovascular diseases, and endothelial dysfunction has a vital role. It has been suggested that inhibiting endothelial cell apoptosis induced by oxidized low-density lipoprotein (ox-LDL), an essential atherosclerotic factor, is a potential novel therapeutic strategy against atherosclerosis. Previous studies have revealed that endothelial lectin-like ox-LDL receptor-1 (LOX-1) and long intergenic noncoding RNA p21 (lincRNA-p21) may serve as therapeutic targets for atherosclerosis and associated cardiovascular disorders. The present study investigated the role of lincRNA-p21 in oxLDL-induced apoptosis and expression of LOX-1 in human coronary artery endothelial cells (HCAECs). Primary HCAECs were treated with ox-LDL (30, 60 or 90 ug/ml) for 24 or 48 h, and the expression of lincRNA-p21, LOX-1 and cell apoptosis rate were measured. Ox-LDL dose- and time-dependently induced the expression of lincRNA-p21 and LOX-1 and apoptosis in HCAECs. Lentiviral overexpression of lincRNA-p21 markedly increased oxLDL-induced apoptosis and the expression of LOX-1 in HCAECs. Additionally, the effect was largely blocked by selective protein kinase C (PKC) inhibitor, rottlerin. However, lentiviral knockdown of lincRNA-p21 markedly decreased oxLDL-induced apoptosis and the expression of LOX-1. In addition, overexpression and knockdown of lincRNA-p21 markedly increased and decreased oxLDL-induced PKCdelta activity/phosphorylation, respectively. In conclusion, to the best of our knowledge, the present study provides the first evidence indicating that lincRNA-p21 is a major mediator of oxLDL-induced apoptosis and expression of LOX-1 in human vascular endothelial cells, and acts via activation of PKCdelta. These results provide insights into the role of lincRNA-p21 in the pathogenesis of atherosclerosis. PMID- 28983629 TI - Expression of carbonic anhydrase III and skeletal muscle remodeling following selective denervation. AB - Carbonic anhydrase III (CAIII) is expressed selectively in type I (slow-twitch) myofibers. To investigate the association between changes in the expression of CAIII and skeletal muscle structure following denervation, the present study stained adjacent sections of skeletal muscle for ATPase and immunohistochemically for CAIII. In addition, differences in the protein expression and phosphatase activity of CAIII were examined by western blot and phosphatase staining between rat soleus and extensol digitorum longus (EDL) muscles, which are composed of predominantly slow- and fast-twitch fibers, respectively. Upon denervation, the EDL muscle showed more pronounced structural changes, compared with the soleus muscle. There was a transformation from fast to slow fibers, and a concomitant increase in fibers positive for CAIII. Following denervation, the protein expression of CAIII initially increased and then decreased in the soleus muscle, whereas the protein expression of CAIII in the EDL muscle increased gradually with time. In contrast to the protein changes, phosphatase activity in the soleus and EDL muscles decreased significantly following denervation. These results indicated that, following denervation, changes in the expression of CAIII were associated with myofiber remodeling. Specifically, the change in the expression of CAIII reflected the conversion to type I myofibers, suggesting the importance of CAIII in resistance to fatigue in skeletal muscle. PMID- 28983631 TI - Integrated analysis reveals candidate genes and transcription factors in lung adenocarcinoma. AB - Lung adenocarcinoma is the most common type of non-small cell lung cancer in Asia. Therefore, it is important to improve understanding of the underlying transcriptional regulatory mechanisms involved. The present study aimed to identify potential candidate genes and transcription factors (TFs) associated with the disease. Four gene expression profiles were downloaded from the Gene Expression Omnibus database, which included 141 lung adenocarcinoma patients and 191 healthy controls. The differentially expressed genes (DEGs) were screened out and functional annotation was performed. In addition, TFs were identified and a global transcriptional regulatory network was constructed. Integrated analysis gave rise to a total of 1,238 DEGs in lung adenocarcinoma when compared with healthy tissues, including 970 upregulated and 268 downregulated DEGs. The six overexpressed outlier genes of ceruloplasmin, heparan sulfate 6-O sulfotransferase 2, transmembrane protease serine 4, anillin actin binding protein, cellular retinoic acid binding protein 2 and cystatin SN may serve important roles in the development of lung adenocarcinoma. In addition, the downregulation of carbonic anhydrase 4 and S100 calcium binding protein A12 may render these effective diagnostic biomarkers. The results of the transcriptional regulatory network demonstrated that the hub nodes were sex determining region Y box 10, Spi-B transcription factor and nuclear receptor subfamily 4 group A member 2. The four TFs, forkhead box D1, E74-like ETS transcription factor 5, homeobox A5 and kruppel-like factor 5, may warrant future investigations into their function in disease development. In conclusion, the present study provided for further studies a list of candidate genes and TFs for the detection and treatment of lung adenocarcinoma. PMID- 28983630 TI - Rebamipide upregulates mucin secretion of intestinal goblet cells via Akt phosphorylation. AB - Mucin is produced and secreted by epithelial goblet cells and is a key component of the innate immune system, acting as a barrier in the intestinal tract. However, no studies have been conducted investigating the increase in mucin secretion to enhance the intestinal barrier function. The present study investigated whether rebamipide (Reb) acts as a secretagogue of intestinal mucin and the underlying mechanisms involved, thereby focusing on the effect on goblet cells. The LS174T cell line was used as goblet cell-like cells. Using Reb-treated LS174T cells, the level of mucin content was assessed by periodic acid-Schiff (PAS) staining, and mucin 2, oligomeric mucus/gel-forming (MUC2) mRNA expression was assessed using quantitative polymerase chain reaction (PCR). Furthermore, MUC2 secretion in the supernatant was quantified by the dot blot method. The present study additionally investigated the involvement of the epidermal growth factor receptor/Akt serine/threonine kinase 1 (Akt) pathway in mucin secretion by western blotting. The results suggested that Reb strongly enhanced the positivity of PAS staining in LS174T cells, thereby suggesting increased intracellular mucin production. The PCR results indicated that Reb significantly increased MUC2 mRNA in whole cell lysate of LS174T cells. In order to assess the subsequent secretion of mucin by LS174T, MUC2 protein expression in the supernatant was assessed using the dot blot method and it was demonstrated that Reb significantly increased the secretion of MUC2 in a concentration-dependent manner. The p-Akt was significantly increased by Reb treatment, and an Akt inhibitor specifically suppressed MUC2 secretion. Overall, Reb increased mucin secretion directly via p Akt. Reb-increased mucin may act as a strong non-specific barrier against pathogenic stimulants in various intestinal diseases. PMID- 28983632 TI - ? PMID- 28983633 TI - ? PMID- 28983634 TI - The 30th international symposium on paediatric surgical research. PMID- 28983635 TI - ? PMID- 28983636 TI - [Importance of surgical treatment for recurrent rectal cancer]. PMID- 28983637 TI - PKC-dependent phosphorylation of Munc18a at Ser313 in activated RBL-2H3 cells. AB - Protein Kinase C (PKC) regulates the release of pro-inflammatory compounds from IgE/antigen-activated mast cells by unknown mechanisms. In this study, we show for the first time that PKC inhibitor Ro-03-0432, which inhibits RBL-2H3 exocytosis/degranulation in a concentration-dependent fashion, prevents the phosphorylation of membrane fusion factor Munc18a at Ser 313. Our study provides fresh evidence that PKC-dependent protein phosphorylation may contribute to the intricate regulation of mast cell degranulation by directly targeting the fusion factors. PMID- 28983639 TI - Ginsenoside-Rb3 inhibits endothelial-mesenchymal transition of cardiac microvascular endothelial cells. AB - BACKGROUND: We investigated the effect of Ginsenoside-Rb3 (Rb3) on the endothelial-to-mesenchymal transition (EMT) of cardiac microvascular endothelial cells (CMVECs) following coxsackievirus B3 (CVB3) infection. METHODS: CMVECs were infected with 100 TCID50 CVB3 (CVB3 group) or treated with Rb3 (Rb3 group); stably cultured CMVECs were used as control. Cells treated with the Pyk2 inhibitor TAE226 and PI3K inhibitor LY294002 were used for additional experiments. Cell viability was assessed with the Cell Counting Kit-8 (CCK8). Expression of CD31 and alpha-smooth muscle actin (alpha-SMA) was evaluated by immunofluorescence (IF) and Western blotting (WB). Expression of Pyk2, PI3K, and AKT was assessed by real-time polymerase chain reaction (RT-PCR) and WB. RESULTS: Cell morphology, including cell pyknosis, and viability were significantly impaired by CVB3 infection (p < 0.05). However, the morphology of the Rb3 group was unaffected. The CCK8 assay showed that viability in the Rb3 group was increased compared with the CVB3 group (p < 0.05). Expression of CD31 decreased and alpha-SMA increased in the CVB3 group compared with the control group (p < 0.05), but CD31 increased while alpha-SMA decreased in the Rb3 group compared with the CVB3 group (p < 0.05). IF staining showed the same trends. The levels of Pyk2, PI3K, AKT, and CD31 were up-regulated in the Rb3 group compared with the CVB3 group, whereas alpha-SMA decreased (p < 0.05). In the Pyk2-inhibitor group, PI3K, AKT, and CD31 expression was down-regulated while alpha-SMA expression increased in comparison with the Rb3 group (p < 0.05). In the PI3K-inhibitor group, the levels of AKT and CD31 decreased while alpha-SMA increased (p < 0.05), although the level of Pyk2 expression showed no obvious change in comparison with the Rb3 group. CONCLUSION: Rb3 inhibited EMT in CMVECs following CVB3 infection via the Pyk2-PI3K-AKT signaling pathway. PMID- 28983638 TI - Bifidobacteria and the infant gut: an example of co-evolution and natural selection. AB - Throughout the human life, the gut microbiota interacts with us in a number of different ways, thereby influencing our health status. The acquisition of such an interactive gut microbiota commences at birth. Medical and environmental factors including diet, antibiotic exposure and mode of delivery are major factors that shape the composition of the microbial communities in the infant gut. Among the most abundant members of the infant microbiota are species belonging to the Bifidobacterium genus, which are believed to confer beneficial effects upon their host. Bifidobacteria may be acquired directly from the mother by vertical transmission and their persistence in the infant gut is associated with their saccharolytic activity toward glycans that are abundant in the infant gut. Here, we discuss the establishment of the infant gut microbiota and the contribution of bifidobacteria to this early life microbial consortium. PMID- 28983641 TI - [Suicidality in German-speaking school psychiatry : Thematization in textbooks from 1803 until the present]. AB - BACKGROUND: This chronology gives an overview about continuities and changes in the perception of suicidality in German-speaking school psychiatry over the past 200+ years. QUESTIONS: This study was guided by the following questions: has suicidality been perceived as regularly being connected to certain mental illnesses? Which other possible causes have been discussed by psychiatrists from the nineteenth century to the beginning of the twenty-first century? What approaches have major psychiatrists adopted towards suicidal patients and threatened suicide? What treatment and preventive strategies have been suggested? METHODOLOGY: First, we compiled a list of the, in our view, most influential textbooks on psychiatry of German-speaking school psychiatry from 1803 until the present. These textbooks were then skim-read for relevant passages on suicidality. The material gained was elicited, classified and analyzed in relation to the questions at hand. Futhermore, an attempt was made to arrive at contextual estimations. RESULTS: Several authors named a certain set of psychiatric illnesses that are assumed to involve or increase the risk of suicide. These illnesses include depression, schizophrenia and also physical illnesses. In nineteenth century textbooks heredity, anatomical anomalies and nationality were discussed as potential influencing factors. In contrast, more recent books discuss models of how suicidal behavior emerges and often refer to the Werther effect. With respect to therapy there is a trend towards therapeutic discussions and modern psychopharmacotherapy. DISCUSSION: Over time, there have been continuities and changes in psychiatrists' approach to suicidality not only as far as clinical aspects are concerned but also the general approach to and management of suicidal patients. PMID- 28983640 TI - A haplotypic variant at the IRGM locus and rs11747270 are related to the susceptibility for chronic periodontitis. AB - OBJECTIVE AND DESIGN: Immunity-regulated GTPase M (IRGM) plays a critical role in the defense against intracellular bacteria by regulating autophagy formation. This direct genetic association study aimed to determine whether variants at the IRGM genetic locus are associated with chronic periodontitis. MATERIALS AND SUBJECTS: Using PCR and melting curve analysis 390 periodontitis patients and 770 healthy controls have been genotyped regarding six polymorphisms in the IRGM gene (rs13361189, rs10065172, rs4958847, rs1000113, rs11747270, rs931058). RESULTS: Frequency distribution of alleles and genotypes for the six polymorphisms were not significantly different between the periodontitis and the control group. Also following stratification according to gender and smoking no significant linkage was found for any of the IRGM variants with periodontitis. Analysis of a subsample of patients revealed a significant association for rs11747270 with severe periodontitis (p = 0.003). Pairwise linkage analysis revealed one block composed of rs13361189, rs10065172, rs4958847, rs1000113 and 11747270 with strong or even complete linkage disequilibrium (r 2 > 0.9). Four haplotypes showed a frequency of > 1%, among which the haplotype C-T-A-T-G was significantly associated with chronic periodontitis (p = 0.0051; OR 4.66, 95% CI 1.41-15.42). CONCLUSIONS: One rare haplotype of the IRGM locus is significantly associated with chronic periodontitis in a German cohort. PMID- 28983642 TI - [Dermoscopically conspiciuous pigmented lesion on the forehead of a young male patient]. PMID- 28983644 TI - [Victor Khrisanfovich Kandinsky (1849-1889) : Contributions of a Russian psychiatrist to the concepts of pseudohallucination and schizophrenias]. AB - The article highlights the important work of the Russian psychiatrist Victor Khrisanfovich Kandinsky. His merits, in particular those in the fields of hallucinations and schizophrenias, have hitherto been neglected despite the fact that several of his articles have been published in German medical journals. He defined the term pseudohallucination in a way which is still common today. For him the criterion which separates it from real hallucinations was that the patient is aware of the fallacy of the phenomena perceived. Furthermore, his concept of ideophrenia can be regarded as a one of the precursors to today's concept of schizophrenias. PMID- 28983643 TI - [Radical prostatectomy in locally advanced prostate cancer]. AB - BACKGROUND: Due to an inverse stage migration, the proportion of patients with more aggressive and locally advanced prostate cancer (PCa) has increased over the last few years. The natural history in these patients shows a higher risk of local complications and worse oncologic outcome. OBJECTIVES: To analyze the impact of radical prostatectomy (RP) in patients with locally advanced PCa. MATERIALS AND METHODS: A review of the literature was performed using PubMed and MEDLINE databases focusing on articles addressing locally advanced PCa. RESULTS: Current guidelines recommend local therapy in patients with locally advanced PCa among other treatment options. Thereby no strong evidence favoring radiotherapy or RP is present. Compared to patients without local treatment, RP may improve oncologic outcome and decrease the risk of local complications. Due to more difficult surgery and an increased need of multimodal therapy, higher perioperative morbidity and worse functional outcomes compared to patients with localized PCa are reported. No reliable prospective data indicating a widespread use of neoadjuvant treatment exists. Indication for further adjuvant or salvage therapies depends on pathologic results and postoperative course. CONCLUSIONS: RP is one of the treatment options with good long-term results which can be offered to patients with locally advanced PCa. Nevertheless, patients need to be counselled especially about the worse postoperative functional outcome compared to patients with localized PCa. PMID- 28983645 TI - [Pseudomonas aeruginosa infections in chronic obstructive pulmonary disease : Role of long-term antibiotic treatment]. AB - Chronic Pseudomonas aeruginosa colonization in the airways of patients with chronic obstructive pulmonary disease (COPD) is probably associated with increased mortality and morbidity and a faster progress of COPD, although this has not been conclusively proven by studies. Studies demonstrating an improvement in prognosis in COPD patients by early eradication of Pseudomonas or at least a reduction of the bacterial burden by either inhaled or oral antibiotic maintenance therapy, are missing. An impact on the exacerbation rate has only been shown for macrolide maintenance treatment; however, this effect could be explained by the inclusion of patients with bronchiectasis in the studies. This is a group of patients for whom the effect of this kind of antibiotic treatment is well known. Further studies on the prevention and treatment of chronic Pseudomonas colonization in COPD patients are urgently needed. The stability of the respiratory microbiome probably plays an essential role in the course of the disease and should be established as a study endpoint. PMID- 28983646 TI - [Practice-oriented pain therapy in dermatology : Concept with special emphasis on pain quality]. AB - In order to avoid chronification of pain, appropriate treatment has to be started as early as possible. Inpatient dermatology patients not only suffer from old age and associated multimorbidities but also from characteristic pain due to distinct dermatological diseases. In many cases clinicians have little experience with specific pain treatment but instead have many concerns about how to deal with analgesics. So far chronic pain has been treated according to the pain ladder of the World Health Organization (WHO), which prioritizes the intensity of pain. This article presents an easily implementable concept of pain therapy with special emphasis on the quality of pain. This provides information on whether it is neuropathic or nociceptive pain, which can ultimately be differentially treated. The primary aim is to provide treating dermatologists with a concept to assist in the initiation of an efficient and correct pain therapy. This brief introduction of an individualized pain treatment can reduce the risk of chronification of pain, which can severely impair the quality of life particularly in dermatology patients and also the frequent stigmatization due to the dermatosis. PMID- 28983647 TI - Focus on fluid therapy. PMID- 28983648 TI - Optimising yield and resource utilisation of summer maize under the conditions of increasing density and reducing nitrogen fertilization. AB - The inefficient use of resources always poses risks of maize (Zea mays L.) yield reduction in China. We performed this research to monitor the effects of increasing plant density and reducing nitrogen (N) rate on radiation-use efficiency (RUE), N efficiency traits, grain yield (GY) and their inter relationships. Besides, whether GY and resource-use efficiency can both be maximized was examined. Hence, a 2-year field experiment was conducted using a widely grown variety "Denghai 618" in Shandong, China. Treatments contained two different plant densities [67,500 (D1) and 97,500 (D2) plant ha-1] and three N levels [0 (N-2), 180 (N-1), 360 (Nck) kg ha-1], set D1Nck as control. Significant increases in grain yield, biomass, RUE, above-ground N uptake (AGN) and N efficiency were observed when density increased from D1 to D2. Declining N application was accompanied by reductions in yield, RUE and AGN especially under high density, yet an obvious improvement in N recovery efficiency (NRE), agronomic N efficiency and N partial factor productivity. The increased GY was positive related with population biomass (r = 0.895**), RUE (r = 0.769**) and AGN (r = 0.923**), whereas it has no significant correlation with N efficiency. In this study, D2Nck obtained 18.8, 17.9, 24.8 and 29.7% higher grain yield, RUE, AGN and NRE respectively, compared to control, optimizing both yield and the efficiencies of radiation and N use. Furthermore, higher yield and RUE with more desirable N efficiency may be possible via optimizing density and N rate combination. PMID- 28983649 TI - [Shoulder cartilage regeneration : Indications, possibilities, surgical implementation]. AB - Asymptomatic cartilage lesions of the shoulder are frequent. Symptomatic lesions are treated analogously to other hyaline cartilage bearing joints and can be treated arthroscopically in the vast majority of cases. The therapeutic options can be subdivided into resection, stimulation and transplantation of the defect cartilage. There are only a few reports about outcome after cartilage restoration surgery in the literature, and microfracturing is the surgical technique that has been most investigated. PMID- 28983650 TI - [Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)]. AB - This article presents the case of a patient with dyspnea, a history of poorly controlled asthma, sinonasal polyposis, blood eosinophilia and transient pulmonary infiltrates. The autoantibodies antinuclear antibodies, cytoplasmic anti-neutrophil cytoplasmic antibodies (c-ANCA) and perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) were negative. These symptoms are typical for eosinophilic granulomatosis with polyangiitis (EGPA, alternatively known as Churg Strauss syndrome). The delay between onset and diagnosis in this case was several years. Although EGPA belongs to the spectrum of ANCA-associated vasculitis, less than 50% of EGPA patients are ANCA positive. Cardiac involvement (such as endomyocardial infiltration, arrhythmia and pericarditis) is the major cause of early death and a poor prognosis. In therapeutic regimens glucocorticoids and/or another immunosuppressant (e. g. cyclophosphamide, methotrexate or azathioprine) are used. The so-called five-factor score is a useful tool for assessment of prognosis. PMID- 28983651 TI - [Cytoreductive, radical prostatectomy in metastatic prostate cancer]. AB - The resection of the primary tumor in patients with metastatic prostate cancer is controversially debated. Retrospective clinical studies indicate survival benefits and prevention of secondary, locoregional complications; however, results of ongoing multicenter prospective studies are still lacking. This review highlights the rationale behind the cytoreductive prostatectomy and summarizes current clinical study results. PMID- 28983652 TI - What the radiologist needs to know about gastrointestinal endoscopic surgical procedures. AB - Natural orifice transluminal endoscopic surgery (NOTES) is a novel surgical approach, currently performed for an array of conditions. Endoscopic procedures offer significant benefits, including lower cost, no surgical incisions, and shorter hospital stays. These advantages align with the current trends in health care, namely a push for "cost-effective care." There are a multitude of health issues which are now being addressed by the endoscopic surgical approach, including peroral endoscopic myotomy (POEM), which is a relatively new technique used in the treatment of achalasia. Endoscopic treatment utilized for GERD includes transoral incisionless fundoplication. Endoscopic bariatric surgical procedures include intragastric balloon placement, endoscopic sleeve gastroplasty, and revision of prior bariatric procedures including Roux-en-Y gastric bypass and conventional gastric sleeve procedures. Endoscopic clips are routinely utilized for achieving hemostasis, treating iatrogenic gastric and bowel ulcerations and perforations and for the closure of enteric fistulization. Novel endoscopic procedures are now replacing conventional surgery due to their non-invasive nature, faster recovery and lower healthcare costs. Radiologists need to understand how these procedures are performed, as well as expected post procedural imaging appearance and potential complications. PMID- 28983653 TI - Combined arthroscopic all-inside repair of lateral and medial ankle ligaments is an effective treatment for rotational ankle instability. AB - PURPOSE: When the anterior fascicle of the deltoid ligament is injured in patients with chronic ankle instability, the diagnosis of rotational ankle instability is supported. The aim of this study was to report the results of an all-arthroscopic technique to concomitantly repair the lateral collateral and deltoid ligaments to treat patients with rotational ankle instability. METHODS: Thirteen patients [12 men and 1 woman, median age 32 (15-54) years] with rotational ankle instability were treated by arthroscopic means after failing non operative management. Median follow-up was 35 (18-42) months. Using a suture passer and knotless anchors, the ligaments were repaired with an arthroscopic all inside technique. RESULTS: During diagnostic arthroscopy, 12 patients showed an isolated anterior talofibular ligament (ATFL) injury, and in one patient, both the ATFL and calcaneofibular ligament were affected. Arthroscopic examination of the deltoid ligament demonstrated a tear affecting the anterior area of the ligament in all cases. The tear was described as an "open book" tear, because the ligament was separated from the medial malleolus when applying passive internal rotation of the tibio-talar joint. This gap was closed when the tibio-talar joint was in neutral rotation or externally rotated. All patients reported subjective improvement in their ankle instability after the arthroscopic all-inside ligaments repair. The median AOFAS score increased from 70 (44-77) preoperatively to 100 (77-100) at final follow-up. CONCLUSION: Rotational ankle instability can be successfully treated by an arthroscopic all-inside repair of the lateral and medial ligaments of the ankle. LEVEL OF EVIDENCE: Level IV, retrospective case series. PMID- 28983654 TI - Imaging and minimally invasive endovascular therapy in the management of portal vein thrombosis. AB - Thrombosis of the portal venous system, although rare in the general population, is commonly diagnosed in patients with specific underlying conditions including prothrombotic diseases, cirrhosis, hepatobiliary malignancy, and intraabdominal inflammation. Recent improvements in imaging have played a fundamental role in increased detection of portal vein thrombosis (PVT), frequently reported in asymptomatic patients as an incidental finding. Minimally invasive, endovascular therapy is a medically rational option to achieve recanalization of the portal vein as an adjunct to conservative medical management. This review focuses on the advances in imaging modalities to diagnose, stage and follow-up PVT, and gives a short overview of the available endovascular techniques in this field. PMID- 28983655 TI - Mechanistic understanding of Phenyllactic acid mediated inhibition of quorum sensing and biofilm development in Pseudomonas aeruginosa. AB - Pseudomonas aeruginosa depends on its quorum sensing (QS) system for its virulence factors' production and biofilm formation. Biofilms of P. aeruginosa on the surface of indwelling catheters are often resistant to antibiotic therapy. Alternative approaches that employ QS inhibitors alone or in combination with antibiotics are being developed to tackle P. aeruginosa infections. Here, we have studied the mechanism of action of 3-Phenyllactic acid (PLA), a QS inhibitory compound produced by Lactobacillus species, against P. aeruginosa PAO1. Our study revealed that PLA inhibited the expression of virulence factors such as pyocyanin, protease, and rhamnolipids that are involved in the biofilm formation of P. aeruginosa PAO1. Swarming motility, another important criterion for biofilm formation of P. aeruginosa PAO1, was also inhibited by PLA. Gene expression, mass spectrometric, functional complementation assays, and in silico data indicated that the quorum quenching and biofilm inhibitory activities of PLA are attributed to its ability to interact with P. aeruginosa QS receptors. PLA antagonistically binds to QS receptors RhlR and PqsR with a higher affinity than its cognate ligands N-butyryl-L-homoserine lactone (C4-HSL) and 2-heptyl-3,4 dihydroxyquinoline (PQS; Pseudomonas quinolone signal). Using an in vivo intraperitoneal catheter-associated medaka fish infection model, we proved that PLA inhibited the initial attachment of P. aeruginosa PAO1 on implanted catheter tubes. Our in vitro and in vivo results revealed the potential of PLA as anti biofilm compound against P. aeruginosa. PMID- 28983656 TI - A topological analysis of targeted In-111 uptake in SPECT images of murine tumors. AB - Single-photon emission computed tomography images of murine tumors are interpreted as the values of functions on a three-dimensional domain. Motivated by Morse theory, the local maxima of the tumor image functions are analyzed. This analysis captures tumor heterogeneity that cannot be identified with standard measures. Utilizing decreasing sequences of uptake values to filter the images, a modified form of the standard persistence diagrams for 0-dimensional persistent homology as well as novel childhood diagrams are constructed. Applying statistical methods to time series of persistence and childhood diagrams detects heterogeneous uptake of radioactive antibody within tumors over time and distinguishes uptake in two groups of mice injected with different labeled antibodies. PMID- 28983657 TI - Efficacy and safety of retreatment with nivolumab in metastatic melanoma patients previously treated with nivolumab. AB - BACKGROUND: Nivolumab is a monoclonal antibody directed against programmed death 1 that has been shown to improve survival in patients with metastatic melanoma. However, the efficacy of nivolumab and other agents in melanoma remains limited. The objective of this study was to evaluate the efficacy and safety of retreatment with nivolumab in metastatic melanoma patients who previously progressed on nivolumab. PATIENTS AND METHODS: A retrospective review was performed on eight consecutive metastatic melanoma patients retreated with nivolumab who progressed on previous nivolumab. These patients received nivolumab 2 mg/kg every 3 weeks. Best responses to each treatment were assessed using RECIST 1.1. RESULTS: Of eight metastatic melanoma patients, three patients received chemotherapy before first nivolumab. The median first nivolumab treatment period was 4.1 months. During first nivolumab, 3 (37.5%) patients achieved a partial response and 3 (37.5%) patients achieved stable disease as their best response. First nivolumab was discontinued due to disease progression in seven patients and grade 3 colitis in 1 patient. Patients were subsequently treated with ipilimumab (n = 6), vemurafenib (n = 1), or no other medical treatment (n = 1). The median treatment period between first and second nivolumab was 3.0 months. Four patients received radiation therapy between first and second nivolumab. The median second nivolumab treatment period was 4.3 months. Among the eight patients who received second nivolumab, 2 (25%) patients achieved a partial response and 3 (37.5%) patients achieved stable disease as their best response. Second nivolumab was discontinued due to disease progression in seven patients. One patient continues to receive second nivolumab. Among the four patients treated with ipilimumab and radiotherapy between first and second nivolumab, the response rate was 50% and the disease control rate was 75%. CONCLUSIONS: This study showed that retreatment with nivolumab is an option for select metastatic melanoma patients after previous nivolumab treatment. PMID- 28983658 TI - Newborn screening for biliary atresia in the United States. AB - Despite advances in our understanding of the pathogenesis of biliary atresia (BA), BA remains the most common cause of end-stage liver disease in children and the leading indication for pediatric liver transplantation. Age at time of Kasai portoenterostomy (KPE), performed to provide bile drainage, strongly correlates with transplant-free survival, mostly due to progression of intrahepatic fibrosis to cirrhosis. Unfortunately, challenges remain in recognizing that a jaundiced infant may have BA. To better diagnose infants with BA at an earlier age, population-based screening programs in countries such as Taiwan, Japan, and China have utilized stool color cards. Early results have been promising demonstrating earlier diagnosis, earlier KPE, and, hence, improved outcomes. Cost-effectiveness studies focused on stool color card screening in North America where the incidence of BA is much lower also project improved transplant-free survival rate with a savings in terms of healthcare expenditure. There is also evidence that postnatal serum bilirubin levels may also be effective as a screening tool given that all infants with BA exhibit hyperbilirubinemia at birth. The American Academy of Pediatrics (AAP) recently advocated studying the implementation of newborn screening for BA in the United States. Further efforts and analyses within the United States are ongoing, but current evidence is supportive of screening for BA even in low incidence countries. PMID- 28983659 TI - Cardiac and peripheral vasomotor autonomic functions in late-onset transthyretin Val30Met familial amyloid polyneuropathy. AB - The objective of this study was to systematically investigate cardiac and peripheral vasomotor autonomic functions in late-onset transthyretin Val30Met familial amyloid polyneuropathy (FAP ATTR Val30Met) patients from non-endemic areas. The coefficient of variation of R-R intervals (CVR-R), responses to the Valsalva manoeuvre, head-up tilt test with impedance cardiography, noradrenaline infusion test, and (123)I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy were assessed in eight patients. Although only four patients manifested orthostatic hypotension during the head-up tilt test, CVR-R, responses to the Valsalva manoeuvre, and myocardial MIBG uptake indicated a higher prevalence of cardiac sympathetic and parasympathetic dysfunction. Total peripheral resistance at 60 degrees tilt did not increase from baseline values in five of six examined patients. An infusion of low-dose noradrenaline induced an increase in systolic blood pressure in all patients. The extent of the change in systolic blood pressure negatively correlated to that in total peripheral resistance (p < 0.05). Patients with poor vasoconstrictor responses to orthostatic stress tended to exhibit severe reduction of unmyelinated fibres in sural nerve biopsy specimens. In conclusion, both cardiac and peripheral vasomotor autonomic dysfunctions were prevalent in late-onset FAP ATTR Val30Met patients from non-endemic areas, even in those without orthostatic intolerance. However, vasoconstriction by alpha adrenoceptor agonists was preserved even after denervation, carrying important implications for the management of orthostatic hypotension in FAP. PMID- 28983661 TI - Low kV versus dual-energy virtual monoenergetic CT imaging for proven liver lesions: what are the advantages and trade-offs in conspicuity and image quality? A pilot study. AB - PURPOSE: Single-energy low tube potential (SE-LTP) and dual-energy virtual monoenergetic (DE-VM) CT images both increase the conspicuity of hepatic lesions by increasing iodine signal. Our purpose was to compare the conspicuity of proven liver lesions, artifacts, and radiologist preferences in dose-matched SE-LTP and DE-VM images. METHODS: Thirty-one patients with 72 proven liver lesions (21 benign, 51 malignant) underwent full-dose contrast-enhanced dual-energy CT (DECT). Half-dose images were obtained using single tube reconstruction of the dual-source SE-LTP projection data (80 or 100 kV), and by inserting noise into dual-energy projection data, with DE-VM images reconstructed from 40 to 70 keV. Three blinded gastrointestinal radiologists evaluated half-dose SE-LTP and DE-VM images, ranking and grading liver lesion conspicuity and diagnostic confidence (4 point scale) on a per-lesion basis. Image quality (noise, artifacts, sharpness) was evaluated, and overall image preference was ranked on per-patient basis. Lesion-to-liver contrast-to-noise ratio (CNR) was compared between techniques. RESULTS: Mean lesion size was 1.5 +/- 1.2 cm. Across the readers, the mean conspicuity ratings for 40, 45, and 50 keV half-dose DE-VM images were superior compared to other half-dose image sets (p < 0.0001). Per-lesion diagnostic confidence was similar between half-dose SE-LTP compared to half-dose DE-VM images (p >= 0.05; 1.19 vs. 1.24-1.32). However, SE-LTP images had less noise and artifacts and were sharper compared to DE-VM images less than 70 keV (p < 0.05). On a per-patient basis, radiologists preferred SE-LTP images the most and preferred 40-50 keV the least (p < 0.0001). Lesion CNR was also higher in SE-LTP images than DE-VM images (p < 0.01). CONCLUSION: For the same applied dose level, liver lesions were more conspicuous using DE-VM compared to SE-LTP; however, SE LTP images were preferred more than any single DE-VM energy level, likely due to lower noise and artifacts. PMID- 28983660 TI - Synthetic genome recoding: new genetic codes for new features. AB - Full genome recoding, or rewriting codon meaning, through chemical synthesis of entire bacterial chromosomes has become feasible in the past several years. Recoding an organism can impart new properties including non-natural amino acid incorporation, virus resistance, and biocontainment. The estimated cost of construction that includes DNA synthesis, assembly by recombination, and troubleshooting, is now comparable to costs of early stage development of drugs or other high-tech products. Here, we discuss several recently published assembly methods and provide some thoughts on the future, including how synthetic efforts might benefit from the analysis of natural recoding processes and organisms that use alternative genetic codes. PMID- 28983662 TI - Radiofrequency ablation for locally advanced pancreatic cancer: SMAD4 analysis segregates a responsive subgroup of patients. AB - PURPOSE: SMAD4 mutational status correlates with pancreatic ductal adenocarcinoma (PDAC) failure pattern. We investigated in a subset of locally advanced patients submitted to radiofrequency ablation (RFA) whether the assessment of SMAD4 status is a useful way to select the patients. METHODS: Clinical, radiological, and follow-up details of patients submitted to RFA for locally advanced pancreatic cancer (LAPC), in whom cytohistological material was available at our institution, were retrospectively retrieved. SMAD4 expression was evaluated by immunohistochemistry (IHC) and considered "negative" or "positive." The survival analysis was conducted using Kaplan-Meier and Cox proportional hazards models. RESULTS: The study population consisted of 30 patients. Thirteen patients (43.3%) received RFA upfront, whereas 17 (56.7%) after induction treatments. SMAD4 was mutant in 18 out of 30 patients (60%). The overall estimated post-RFA disease specific survival (DSS) was 15 months (95% CI 11.64-18.35). The estimated post RFA DSS of patients with wild-type and mutant SMAD4 was 22 and 12 months, respectively (log-rank p < 0.05). At the multivariate analysis, SMAD4 was the only independent predictor of survival (p = 0.05). The pattern of failure was not associated with SMAD4 status (p = 0.4). CONCLUSIONS: Within patients undergoing RFA for LAPC, SMAD4 analysis could segregate a subgroup of subjects with improved survival, who likely benefited from tumor ablation. PMID- 28983663 TI - The role of land and aquatic exercise in ankylosing spondylitis: a systematic review. AB - Ankylosing spondylitis (AS) is a chronic and inflammatory rheumatic disease, characterized by pain and structural and functional impairments, such as reduced mobility and axial deformity, which lead to diminished quality of life. Its treatment includes not only drugs, but also nonpharmacological therapy. Exercise appears to be a promising modality. The aim of this study is to review the current evidence and evaluate the role of exercise either on land or in water for the management of patients with AS in the biological era. Systematic review of the literature published until November 2016 in Medline, Embase, Cochrane Library, Web of Science and Scopus databases. Thirty-five studies were included for further analysis (30 concerning land exercise and 5 concerning water exercise; combined or not with biological drugs), comprising a total of 2515 patients. Most studies showed a positive effect of exercise on Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, pain, mobility, function and quality of life. The benefit was statistically significant in randomized controlled trials. Results support a multimodal approach, including educational sessions and maintaining home-based program. This study highlights the important role of exercise in management of AS, therefore it should be encouraged and individually prescribed. More studies with good methodological quality are needed to strengthen the results and to define the specific characteristics of exercise programs that determine better results. PMID- 28983664 TI - [Radiation therapy of locally advanced prostate cancer]. AB - The risk classification for localized prostate cancer is based on the groups "low", "intermediate", and "high-risk" prostate cancer. Following this established risk group definition, locally advanced prostate cancer (cT3/4N0M0) has to be classified as "high-risk" prostate cancer. Radical prostatectomy or high-dose radiotherapy, which is combined with androgen deprivation, are the only curative standard treatments for locally advanced prostate cancer. Particularly adequate radiation doses, modern radiotherapy techniques like IMRT/IGRT, as well as long-term androgen suppression are essential for an optimal treatment outcome. In combination with definitive radiotherapy, androgen deprivation therapy should be started neoadjuvant/simultaneous to radiotherapy and is recommended to be continued after radiotherapy. Previous data suggest that 2-year long-term androgen deprivation in this setting may not be inferior to 3-year long-term androgen deprivation in high-risk patients. An additional radiation therapy of the lymphatic pathways in men with cN0 locally advanced/high-risk prostate cancer is still a matter of research. Ongoing trials may define selected subgroups with a suggested benefit at its best. PMID- 28983665 TI - The effect of prebiotic vaginal gel with adjuvant oral metronidazole tablets on treatment and recurrence of bacterial vaginosis: a triple-blind randomized controlled study. AB - PURPOSE: Bacterial vaginosis is a change in the normal vaginal bacterial flora that leads to loss of hydrogen peroxide producing lactobacilli and overgrowth of predominantly anaerobic bacteria. The present study was conducted to compare the effects of prebiotic vaginal gel with oral metronidazole tablet and metronidazole tablet alone on treatment and recurrence of bacterial vaginosis. METHODS: The present triple-blind randomized clinical trial was conducted in Sadatmandi Hospital in Robat-Karim town, where 100 patients were randomly divided into intervention (receiving a 5 mg prebiotic vaginal gel applicator plus three 250 mg metronidazole tablets per day for 7 days) and control (receiving a 5 mg placebo vaginal gel applicator and three 250 mg metronidazole tablets per day for 7 days) groups. Then, patients were assessed for bacterial vaginosis on 90 +/- 3 day after treatment. Data collected were analyzed in SPSS-21 using Chi square, repeated measures, and student's t tests at a significance level of P < 0.05. RESULTS: The results obtained showed no significant difference between the two groups in terms of personal and social characteristics, clinical complaints, or laboratory markers. On the 10th day, healing rate based on Amsel and Nugent criteria was 76% in the intervention group and 30% in the control group [odds ratio (OR) 4.3; 95% confidence interval (CI) 2.7-9.4]. On the 90th day, healing rate was 84% in the intervention group and 62% in the control group (OR 3.7; 95% CI 1.3-8.9). CONCLUSIONS: Adjuvant treatment with prebiotic vaginal gel improves the efficacy of bacterial vaginosis treatment. PMID- 28983666 TI - Assessment of reliability, validity, responsiveness and minimally important change of the German Hip dysfunction and osteoarthritis outcome score (HOOS) in patients with osteoarthritis of the hip. AB - Patient-reported outcome measures are a critical tool in evaluating the efficacy of orthopedic procedures. The intention of this study was to evaluate reliability, validity, responsiveness and minimally important change of the German version of the Hip dysfunction and osteoarthritis outcome score (HOOS). The German HOOS was investigated in 251 consecutive patients before and 6 months after total hip arthroplasty. All patients completed HOOS, Oxford-Hip Score, Short-Form (SF-36) and numeric scales for pain and disability. Test-retest reliability, internal consistency, floor and ceiling effects, construct validity and minimal important change were analyzed. The German HOOS demonstrated excellent test-retest reliability with intraclass correlation coefficient values > 0.7. Cronbach's alpha values demonstrated strong internal consistency. As hypothesized, HOOS subscales strongly correlated with corresponding OHS and SF-36 domains. All subscales showed excellent (effect size/standardized response means > 0.8) responsiveness between preoperative assessment and postoperative follow up. The HOOS and all subdomains showed higher changes than the minimal detectable change which indicates true changes. The German version of the HOOS demonstrated good psychometric properties. It proved to be valid, reliable and responsive to the changes instrument for use in patients with hip osteoarthritis undergoing total hip replacement. PMID- 28983667 TI - Utility of adult-based ultrasound malignancy risk stratifications in pediatric thyroid nodules. AB - BACKGROUND: Individual ultrasound (US) features have limited ability to distinguish benign from malignant thyroid nodules. Adult-based systems have been developed to integrate the sonographic features in an effort to improve diagnostic accuracy. None, however, has been validated in children, in whom the likelihood of malignancy is 2-5 times higher than adults. OBJECTIVE: To assess the performance of two adult-based sonographic (US) stratification methods for assessment of thyroid nodules in children. MATERIALS AND METHODS: This retrospective study comprised 124 children who underwent thyroid US. Three radiologists reviewed the US data using the American Thyroid Association (ATA) and the Thyroid Image Reporting and Data System (TI-RADS). Radiologists' accuracy and agreement was assessed. The reference standard was histopathology/cytology or 2-year follow-up of clinical outcome for nonoperative cases. RESULTS: We assessed 71 benign and 52 malignant nodules and excluded 1 nodule. Using the ATA pattern descriptions, 80% of malignant nodules were classified as "high" 36/52 (69%) or "intermediate" 6/52 (11%) likelihood of malignancy. A total of 20/71 (28%) benign nodules were also classified within these two categories. Using the TI-RADS, malignant nodules were classified as 2, 3, 4a, 4b, 4c and 5, with rate of malignancy of 0%, 0%, 7/52 (13.5%), 7/52 (13.5%), 32/52 (61.5%) and 6/52 (11.5%), respectively. Benign nodules were also classified in the 4a (26/71; 36.6%), 4b (17/71; 24%), 4c (14/71; 19.7%) and 5 (1/71; 1.4%) categories. The positive and negative predictive values were 68.0% and 87.5% for ATA, and 71.7% and 80.0% for TI-RADS. CONCLUSION: We validated the use of ATA and TI-RADS methods in children and showed that they have test characteristics similar to those in adults, although neither is independently sufficient to discriminate nodules' likelihood of malignancy. PMID- 28983668 TI - YC-1 alleviates bone loss in ovariectomized rats by inhibiting bone resorption and inducing extrinsic apoptosis in osteoclasts. AB - Osteoporosis is a major health problem in postmenopausal women and the elderly that leads to fractures associated with substantial morbidity and mortality. Current osteoporosis therapies have significant drawbacks, and the risk of fragility fractures has not yet been eliminated. There remains an unmet need for a broader range of therapeutics. Previous studies have shown that YC-1 has important regulatory functions in the cardiovascular and nervous systems. Many of the YC-1 effector molecules in platelets, smooth muscle cells and neurons, such as cGMP and MU-calpain, also have important functions in osteoclasts. In this study, we explored the effects of YC-1 on bone remodeling and determined the potential of YC-1 as a treatment for postmenopausal osteoporosis. Micro-computed tomography of lumbar vertebrae showed that YC-1 significantly improved trabecular bone microarchitecture in ovariectomized rats compared with sham-operated rats. YC-1 also significantly reversed the increases in serum bone resorption and formation in these rats, as measured by enzyme immunoassays for serum CTX-1 and P1NP, respectively. Actin ring and pit formation assays and TRAP staining analysis showed that YC-1 inhibited osteoclast activity and survival. YC-1 induced extrinsic apoptosis in osteoclasts by activating caspase-3 and caspase-8. In osteoclasts, YC-1 stimulated MU-calpain activity and inhibited Src activity. Our findings provide proof-of-concept for YC-1 as a novel antiresorptive treatment strategy for postmenopausal osteoporosis, confirming an important role of nitric oxide/cGMP/protein kinase G signaling in bone. PMID- 28983669 TI - Effects of acaricide treatment and host intrinsic factors on tick acquisition and mortality in Boran cattle. AB - Ticks and associated pathogens pose serious threats to the health of livestock. To assess the efficacy of acaricide dip treatment (cypermethrin, chlorpyrifos, piperonyl butoxide, citronella), we assessed post-treatment tick acquisition and tick mortality of free-ranging Boran cattle inhabiting a wildlife-cattle ranch in Northern Tanzania. Because host intrinsic variables and exposure to ticks may substantially affect tick acquisition, we incorporated host sex, body mass, health condition, and distance traveled in models of tick acquisition. Using generalized linear mixed models that accounted for non-independence of individuals, we found that tick species richness increased with host body mass but was not significantly related to other factors. In contrast, tick abundance increased with time since acaricide treatment, was positively correlated with host body mass, and was higher in female than male cattle. Distance traveled and health condition did not predict tick acquisition. Overall, these patterns were similar when separately analyzing acquisition of the more common tick species (Rhipicephalus pulchellus, R. sanguineus sensu lato, and R. praetextatus). Logistic regression models suggested that tick mortality was high for a few days after acaricide dip treatment but declined steeply post-treatment; 3.5 days after treatment, only 50% of ticks were dead, and mortality declined further thereafter. Our results provide new information regarding tick acquisition patterns in this system including female-biased tick parasitism and support for the hypothesis that increased host body mass provides greater resources and thus supports higher ectoparasite abundance and species richness. The limited acaricide duration of action and effectiveness on all tick species calls for adjusting tick management practices. PMID- 28983671 TI - Molecular modeling studies of structural properties of polyvinyl alcohol: a comparative study using INTERFACE force field. AB - Polyvinyl alcohol (PVA) is a material with a variety of applications in separation, biotechnology, and biomedicine. Using combined Monte Carlo and molecular dynamics techniques, we present an extensive comparative study of second- and third-generation force fields Universal, COMPASS, COMPASS II, PCFF, and the newly developed INTERFACE, as applied to this system. In particular, we show that an INTERFACE force field provides a possibility of composing a reliable atomistic model to reproduce density change of PVA matrix in a narrow temperature range (298-348 K) and calculate a thermal expansion coefficient with reasonable accuracy. Thus, the INTERFACE force field may be used to predict mechanical properties of the PVA system, being a scaffold for hydrogels, with much greater accuracy than latter approaches. Graphical abstract Molecular Dynamics and Monte Carlo studies indicate that it is possible to predict properties of the PVA in narrow temperature range by using the INTERFACE force field. PMID- 28983670 TI - Analgesia (mis)usage on a dental emergency service: a patient survey. AB - OBJECTIVES: Analgesics are one of the most frequently used medicines. Self medication and misuse have been described in the literature. The purpose of this study was to document analgesic (mis)use in a population seeking emergency dental treatment. MATERIAL AND METHODS: Patients consulting a dental emergency service were randomly asked to complete a questionnaire on analgesic use, knowledge and information on the analgesics and on their pain history. A photobook was used as an aid to identify products used. Descriptive statistics were combined with chi square and Mann-Whitney U testing. RESULTS: Ninety-eight patients were included. Acetaminophen (69.4%) and ibuprofen (65.3%) were the most frequently used products. Nearly half of the subjects (43.9%) combined at least two analgesics. Although 42.9% of subjects were aware of the maximum daily dose, 62.2% of the subjects exceeded this limit, specifically 76.6% of subjects using ibuprofen and 32.4% of subjects using acetaminophen overdosing. Females overdosed significantly more than males. Ingestion on medical advice did not affect the overdose rates significantly. No significant relation was found between the absence of knowledge on the maximum daily dose and actual overdosing. No higher pain reduction was found in patients overdosing analgesics. The average number of days patients experienced pain before consulting the emergency unit was 12. A significant relation was found between the lag time and overdosing. CONCLUSIONS: A large portion of the patients overdosed analgesics. Even prior medical advice did not reduce significantly overdose rates. CLINICAL RELEVANCE: Dentists treating emergency cases clearly need to be aware of the high risk and high rates of overdosing analgesics in their patients. PMID- 28983672 TI - Comparative analysis of microbial communities associated with bacteriomes, reproductive organs and eggs of the cicada Subpsaltria yangi. AB - Plant sap-feeding insects of Hemiptera often form intimate symbioses with microbes to obtain nutrients. The cicada Subpsaltria yangi is the only species of the subfamily Tettigadinae known from China. Using high-throughput sequencing combined with fluorescence in situ hybridization analysis, we characterize the bacterial composition of the bacteriomes, testes, ovaries and eggs of two representative populations of this species which occur in different habitats and feed on different plant hosts. In both populations, the bacterial community diversity in the testes was significantly higher than that in other tissues. The obligate endosymbiont Candidatus Sulcia muelleri was observed in all samples and was dominant in the bacteriomes, ovaries and eggs. The usual co-resident endosymbiont Candidatus Hodgkinia cicadicola found in some other cicadas was not detected. Instead, a novel Rhizobiales bacterium which shows a ~ 81% 16S rDNA similarity to Ca. Hodgkinia cicadicola was detected. Given that the genome of Ca. Hodgkinia cicadicola exhibits rapid evolution, it is possible that this novel Rhizobiales bacterium is a related endosymbiont with beneficial trophic functions similar to that of Ca. Hodgkinia cicadicola hosted by several certain other cicadas. The presence of the novel Rhizobiales species in other cicadas and its involvement with the adaptive evolution of related cicada hosts require further investigation. Discrepancy of bacterial communities associated with testes between the two populations may be closely related to the geographic isolation and divergence of habitats and host plants. Our results are informative for further studies of evolutionary divergence of related endosymbionts hosted in cicadas. PMID- 28983673 TI - Left ventricular outflow tract closure during LVAD implantation: 2 cases of patients supported for over 6 years. AB - We previously reported a series of 5 patients with advanced heart failure and aortic insufficiency (AI) who underwent concomitant left ventricular outflow tract (LVOT) closure at the time of continuous-flow left ventricular assist device (CF-LVAD) implantation. Although this technique of treating AI has been shown to be effective in the short term, its long-term durability has not been well studied. Here, we report the long-term outcomes of two patients with severe AI who underwent LVOT closure at the time of CF-LVAD implantation. Each of the two patients survived for more than 6 years without any complications related to LVOT closure. PMID- 28983674 TI - Contrast-enhanced ultrasound (CEUS) of the abdominal vasculature. AB - Vascular diseases account for a significant proportion of abdominal pathology and represent a common referral source for abdominal ultrasonographic examinations. B mode, color Doppler, and spectral Doppler analyses are well-established in the evaluation of abdominal blood vessels although they may occasionally be limited by lower sensitivity for slow flow visualization or the deeper location of abdominal vascular structures. The introduction of microbubbles as ultrasonographic contrast agents has rendered contrast-enhanced ultrasound (CEUS), a valuable complementary ultrasonographic technique, which is capable of addressing clinically significant problems and guiding patient management. The purpose of this pictorial review is to analyze the use of CEUS in the evaluation of abdominal vascular pathology and illustrate such applications by presenting representative images. Pathology discussed includes abdominal aortic aneurysm, post-endovascular treatment aorta, portal vein thrombosis, abdominal vascular trauma, and organ transplantation along with its complications. PMID- 28983675 TI - Efficacy and safety of sofosbuvir plus ribavirin for treatment of cirrhotic patients with genotype 4 hepatitis C virus in real-life clinical practice. AB - Egypt has the highest hepatitis C virus (HCV) prevalence in the world. Sofosbuvir is a new highly effective drug for treatment of HCV infection. Compared to previous treatments, sofosbuvir-based regimens provide a higher cure rate, fewer side effects, and a two- to fourfold reduced duration of therapy. The aim of this study was to evaluate the antiviral efficacy, safety, and tolerability of sofosbuvir plus ribavirin in Egyptian patients with liver cirrhosis due to chronic HCV infection. We studied 2400 cirrhotic Egyptian patients with chronic HCV infection who were treated with dual therapy with sofosbuvir and ribavirin for 24 weeks. Efficacy was determined by assessment of serum HCV RNA. Any adverse events during treatment were recorded. Two thousand four hundred cirrhotic Egyptian patients with chronic HCV infection treated with sofosbuvir and ribavirin for 24 weeks were enrolled in the study. The mean age of the studied group (+/- SD) was 53.9 +/- 6.5 years, 1549 (64.54%) were males, all were cirrhotic patients, 3.41% were treatment-experienced, the baseline mean HCV RNA concentration was 4.33 * 106 IU/mL, and 94.37% of the patients had completed the full course of therapy. The overall SVR12 rate was 71.2%. The most common adverse events were fatigue, myalgia, headache, insomnia, and anemia. One hundred thirty five (5.63%) patients stopped treatment permanently due to the appearance of complications that prevented continuation of treatment. The sofosbuvir and ribavirin combination is safe and effective in treatment of HCV patients with liver cirrhosis. However, further studies are needed to establish the optimal treatment regimen for those cases. PMID- 28983676 TI - The effectiveness of robotic training depends on motor task characteristics. AB - Previous research suggests that the effectiveness of robotic training depends on the motor task to be learned. However, it is still an open question which specific task's characteristics influence the efficacy of error-modulating training strategies. Motor tasks can be classified based on the time characteristics of the task, in particular the task's duration (discrete vs. continuous). Continuous tasks require movements without distinct beginning or end. Discrete tasks require fast movements that include well-defined postures at the beginning and the end. We developed two games, one that requires a continuous movement-a tracking task-and one that requires discrete movements-a fast reaching task. We conducted an experiment with thirty healthy subjects to evaluate the effectiveness of three error-modulating training strategies-no guidance, error amplification (i.e., repulsive forces proportional to errors) and haptic guidance on self-reported motivation and learning of the continuous and discrete games. Training with error amplification resulted in better motor learning than haptic guidance, besides the fact that error amplification reduced subjects' interest/enjoyment and perceived competence during training. Only subjects trained with error amplification improved their performance after training the discrete game. In fact, subjects trained without guidance improved the performance in the continuous game significantly more than in the discrete game, probably because the continuous task required greater attentional levels. Error amplifying training strategies have a great potential to provoke better motor learning in continuous and discrete tasks. However, their long-lasting negative effects on motivation might limit their applicability in intense neurorehabilitation programs. PMID- 28983677 TI - Reduced-dose C-arm computed tomography applications at a pediatric institution. AB - BACKGROUND: Reduced-dose C-arm computed tomography (CT) uses flat-panel detectors to acquire real-time 3-D images in the interventional radiology suite to assist with anatomical localization and procedure planning. OBJECTIVE: To describe dose reduction techniques for C-arm CT at a pediatric institution and to provide guidance for implementation. MATERIALS AND METHODS: We conducted a 5-year retrospective study on procedures using an institution-specific reduced-dose protocol: 5 or 8 s Dyna Rotation, 248/396 projection images/acquisition and 0.1 0.17 MUGy/projection dose at the detector with 0.3/0.6/0.9-mm copper (Cu) filtration. We categorized cases by procedure type and average patient age and calculated C-arm CT and total dose area product (DAP). RESULTS: Two hundred twenty-two C-arm CT-guided procedures were performed with a dose-reduction protocol. The most common procedures were temporomandibular and sacroiliac joint injections (48.6%) and sclerotherapy (34.2%). C-arm CT was utilized in cases of difficult percutaneous access in less common applications such as cecostomy and gastrostomy placement, foreign body retrieval and thoracentesis. C-arm CT accounted for between 9.9% and 80.7% of the total procedural DAP. CONCLUSION: Dose-reducing techniques can preserve image quality for intervention while reducing radiation exposure to the child. This technology has multiple applications within pediatric interventional radiology and can be considered as an adjunctive imaging tool in a variety of procedures, particularly when percutaneous access is challenging despite routine fluoroscopic or ultrasound guidance. PMID- 28983678 TI - The effect of quercetin on the pharmacokinetics of chlorzoxazone, a CYP2E1 substrate, in healthy subjects. AB - PURPOSE: Previous in vitro studies have demonstrated that quercetin inhibits CYP2E1 enzyme, but there are no available data to indicate that quercetin inhibits CYP2E1 enzyme in humans. The purpose of the present study was to assess the effect of quercetin on CYP2E1 enzyme activity in healthy subjects using chlorzoxazone (CHZ) as a CYP2E1 substrate. METHODS: An open-label, two-period, sequential study was conducted in 12 healthy subjects. A single dose of CHZ 250 mg was given to subjects during control phase and after treatment phases. Quercetin at a dose of 500 mg was given to subjects twice daily for a period of 10 days. The blood samples were collected at predetermined time intervals after CHZ dosing and analyzed to determine the concentrations of CHZ and 6 hydroxychlorzoxazone (6-OHCHZ). RESULTS: Treatment with quercetin significantly enhanced the maximum plasma concentration (C max), area under the curve (AUC), and half-life (t 1/2) by 47.8, 69.3, and 36.4%, respectively, while significantly decreased the elimination rate constant (k el) and apparent oral clearance (CL/F) of CHZ by 25.1 and 41.6%, respectively, in comparison with the control. On the other hand, C max and AUC of 6-OHCHZ were decreased by 30.1 and 32.6%, respectively, after quercetin treatment when compared to control. In addition, geometric mean ratios and 90% confidence intervals for C max and AUC of CHZ and 6 OHCHZ were both out of the no-effect boundaries of 0.80-1.25, which indicates a significant pharmacokinetic interaction present between CHZ and quercetin. Furthermore, treatment with quercetin significantly decreased the metabolic ratios of C max and AUC by 57.1 and 60.1%, respectively, as compared to control suggesting that reduced formation of CHZ to 6-OHCHZ. CONCLUSIONS: The results suggest that altered pharmacokinetics of CHZ might be attributed to quercetin mediated inhibition of CYP2E1 enzyme. Further, the inhibition of CYP2E1 by quercetin may represent a novel therapeutic approach for minimizing the ethanol induced CYP2E1 enzyme activity and results in reduced hepatotoxicity of ethanol. PMID- 28983679 TI - Safety of omitting routine bleeding tests prior to image-guided musculoskeletal core needle biopsy. AB - PURPOSE: To evaluate the safety of withholding preprocedure international normalized ratio (INR) and platelet testing in patients undergoing musculoskeletal (MSK) core needle biopsy (CNB). MATERIAL AND METHODS: Initially, a retrospective review of 1,162 consecutive patients undergoing MSK CNB with preprocedural INR and platelet testing was performed. Clinical (age, gender, bleeding disorder, liver disease, anticoagulation use, INR > 2, platelet count <50,000/ul) and biopsy factors (imaging modality, lesion type, biopsy needle gauge, number biopsy samples) were tested for association with bleeding complications. During the second phase, an additional 188 biopsies performed without preprocedural coagulation testing were studied. Categorical variables were compared using Chi-squared or Fisher's exact tests, continuous variables with a student t-test. Multivariate analysis was performed using logistic regression. RESULTS: In the first phase, there was a complication rate of 2.6%, 30/1162. Of the 11 clinical and biopsy factors, soft tissue lesions (p = 0.029) and lesions biopsied under ultrasound (p = 0.048) had a higher rate of bleeding than bone lesions or lesions biopsied under CT, respectively. Only three patients had an INR >2, 0.3% (3/1162) and only four patients had platelet count <50,000/ul, 0.3% (4/1162). No patient with a bleeding complication had an abnormal preprocedure bleeding test. In the second phase, there was a bleeding complication rate of 1.1% (2/188). CONCLUSION: Bleeding complications from MSK biopsy are low, even when preprocedure coagulation testing is omitted. PMID- 28983680 TI - [Community-based psychosocial care for people with dementia]. PMID- 28983681 TI - Altered expression of laminin alpha1 in aganglionic colon of endothelin receptor B null mouse model of Hirschsprung's disease. AB - PURPOSE: Laminin, an extracellular matrix molecule, is essential for normal development of the nervous system. The alpha1 subunit of laminin-1 (LAMA1) has been reported to promote neurites and outgrowth and is expressed only during embryogenesis. Previously, we developed a Sox10 transgenic version of the Endothelin receptor-B (Ednrb) mouse to visualize Enteric neural crest-derived cell (ENCC)s with a green fluorescent protein, Venus. We designed this study to investigate the expression of LAMA1 using Sox10-VENUS mice gut. METHODS: We harvested the gut on days 13.5 (E13.5) and 15.5 (E15.5) of gestation. Sox10 VENUS+/Ednrb -/- mice (n = 8) were compared with Sox10-VENUS+/Ednrb +/+ mice (n = 8) as controls. Gene expression of LAMA1 was analysed by real-time RT-PCR. Fluorescent immunohistochemistry was performed to assess protein distribution. RESULTS: The relative mRNA expression levels of LAMA1 were significantly increased in HD in the proximal and distal colon on E15.5 compared to controls (p < 0.05), whereas there were no significant differences on E13.5. LAMA1 was expressed in the serosa, submucosa and basal lamina in the gut, and was markedly increased in the proximal and distal colon of HD on E15.5. CONCLUSIONS: Altered LAMA1 expression in the aganglionic region may contribute to impaired ENCC migration, resulting in HD. These data could help in understanding the pathophysiologic interactions between LAMA1 and ENCC migration. PMID- 28983683 TI - In vivo Metabolic Profiles as Determined by 31P and short TE 1H MR-Spectroscopy : No Difference Between Patients with IDH Wildtype and IDH Mutant Gliomas. AB - PURPOSE: Previous ex vivo spectroscopic data from tissue samples revealed differences in phospholipid metabolites between isocitrate dehydrogenase mutated (IDHmut) and IDH wildtype (IDHwt) gliomas. We investigated whether these changes can be found in vivo using 1H-decoupled 31P magnetic resonance spectroscopic imaging (MRSI) with 3D chemical shift imaging (CSI) at 3 T in patients with low and high-grade gliomas. METHODS: The study included 33 prospectively enrolled, mostly untreated patients who met spectral quality criteria according to the World Health Organization (WHO II n = 7, WHO III n = 17, WHO IV n = 9; 25 patients IDHmut, 8 patients IDHwt). The MRSI protocol included 1H decoupled 31P MRSI with 3D CSI (3D 31P CSI), 2D 1H CSI and a 1H single voxel spectroscopy sequence (TE 30 ms) from the tumor area. For 1H MRS, absolute metabolite concentration values were calculated (phantom replacement method). For 31P MRS, metabolite intensity ratios were calculated for the choline (C) and ethanolamine (E)-containing metabolites. RESULTS: In our patient cohort we did not find significant differences for the ratio of phosphocholine (PC) and phosphoethanolamine (PE), PC/PE, (p = 0.24) for IDHmut compared to IDHwt gliomas. Furthermore, we found no elevated ratios of glycerophosphocholine (GPC) and glycerophosphoethanolamine (GPE), GPC/GPE, (p = 0.68) or GPC/PE (p = 0.12) for IDHmut gliomas. Even the ratio (PC+GPC)/(PE+GPE) showed no significant differences with respect to mutation status (p = 0.16). Nonetheless, changes related to tumor grade regarding intracellular pH (pHi) and phospholipid metabolism as well as absolute metabolite concentrations of co-registered 2D 1H CSI data for tumor and control tissue showed the anticipated results. CONCLUSION: Using 3D-CSI data acquisition, in vivo 31P MR spectroscopic measurement of phospholipid metabolites could not distinguish between IDHmut and IDHwt. PMID- 28983682 TI - Biliary atresia: unity in diversity. AB - Biliary atresia (BA) is a rare disease of unknown origin and unsatisfying outcome. Single, multicenter and national evaluations of epidemiological and outcome data on BA have been periodically published over the course of decades. However, the diversity of the registered parameters and outcome measures impede comparability and cumulative analysis of these very worthwhile studies. Taking into account the fact that BA is a good example of translational research and transition of patients from pediatric surgery and hepatology to transplant surgery and hepatology in general, the interdisciplinary community should make every effort to develop a common platform upon which further activities are conducted. Extending this topic to BA-related diseases might increase the acceptance of research studies and enhance the effectiveness of any recommendations outlined therein. The use of the Internet-based communication platform and registry on http://www.bard-online.com represents the first step in this direction, and the database should be viewed as a helpful tool that guides further activities. PMID- 28983684 TI - A Rapid Review of eHealth Interventions Addressing the Continuum of HIV Care (2007-2017). AB - National HIV prevention goals call for interventions that address Continuum of HIV Care (CoC) for persons living with HIV. Electronic health (eHealth) can leverage technology to rapidly develop and disseminate such interventions. We conducted a qualitative review to synthesize (a) technology types, (b) CoC outcomes, (c) theoretical frameworks, and (d) behavior change mechanisms. This rapid review of eHealth, HIV-related articles (2007-2017) focused on technology based interventions that reported CoC-related outcomes. Forty-five studies met inclusion criteria. Mobile texting was the most commonly reported technology (44.4%, k = 20). About 75% (k = 34) of studies showed proven or preliminary efficacy for improving CoC-related outcomes. Most studies (60%, k = 27) focused on medication adherence; 20% (k = 9) measured virologic suppression. Many eHealth interventions with preliminary or proven efficacy relied on mobile technology and integrated knowledge/cognition as behavior change mechanisms. This review identified gaps in development and application of eHealth interventions regarding CoC. PMID- 28983685 TI - Congenic mice demonstrate the presence of QTLs conferring obesity and hypercholesterolemia on chromosome 1 in the TALLYHO mouse. AB - The TALLYHO (TH) mouse presents a metabolic syndrome of obesity, type 2 diabetes, and hyperlipidemia. Highly significant quantitative trait loci (QTLs) linked to adiposity and hypercholesterolemia were previously identified on chromosome (Chr) 1 in a genome-wide scan of F2 mice from C57BL/6J (B6) x TH. In this study, we generated congenic mouse strains that carry the Chr 1 QTLs derived from TH on a B6 background; B6.TH-Chr1-128Mb (128Mb in size) and B6.TH-Chr1-92Mb (92Mb in size, proximally overlapping). We characterized these congenic mice on chow and high fat (HF) diets. On chow, B6.TH-Chr1-128Mb congenic mice exhibited a slightly larger body fat mass compared with B6.TH-Chr1-92Mb congenic and B6 mice, while body fat mass between B6.TH-Chr1-92Mb congenic and B6 mice was comparable. Plasma total cholesterol levels were significantly higher in B6.TH-Chr1-128Mb congenics compared to B6.TH-Chr1-92Mb congenic and B6 mice. Again, there was no difference in plasma total cholesterol levels between B6.TH-Chr1-92Mb congenic and B6 mice. All animals gained more body fat and exhibited higher plasma total cholesterol levels when fed HF diets than fed chow, but these increases were greater in B6.TH Chr1-128Mb congenics than in B6.TH-Chr1-92Mb congenic and B6 mice. These results confirmed the effect of the 128Mb TH segment from Chr 1 on body fat and plasma cholesterol values and showed that the distal segment of Chr 1 from TH is necessary to cause both phenotypes. Through bioinformatic approaches, we generated a list of potential candidate genes within the distal region of Chr 1 and tested Ifi202b and Apoa2. We conclude that Chr 1 QTLs largely confer obesity and hypercholesterolemia in TH mice and can be promising targets for identifying susceptibility genes. Congenic mouse strains will be a valuable resource for gene identification. PMID- 28983686 TI - 8beta-OH-THC and 8beta,11-diOH-THC-minor metabolites with major informative value? AB - The ?9-tetrahydrocannabinol (THC) metabolites 8beta-hydroxy-THC and 8beta,11 dihydroxy-THC are mentioned in the literature as potential blood markers of recent cannabis use. However, the formation of these metabolites in in vivo detectable concentrations has been described controversially. Therefore, the aim of this study was to verify the in vivo metabolism of 8beta-hydroxy-THC and 8beta,11-dihydroxy-THC in order to evaluate their potential as blood markers of recent cannabis use. First, we developed and validated a solid-phase-extraction method coupled with gas chromatography-mass spectrometry in order to enable the selective and very sensitive determination of 8beta-hydroxy-THC and 8beta,11 dihydroxy-THC. The application of this method in the analysis of 70 authentic plasma samples of cannabis users revealed positive results for both analytes. We detected 8beta-hydroxy-THC in three and 8beta,11-dihydroxy-THC in 37 out of the 70 analyzed samples. For 8beta-hydroxy-THC, all of the three positive results were below the limit of quantification (LOQ; 0.3 ng/mL) but above the limit of detection (LOD; 0.2 ng/mL). For 8beta,11-dihydroxy-THC, only two positive results were below the LOQ (0.4 ng/mL) but above the LOD (0.3 ng/mL); the remaining 35 were quantified. Hence, we were able to prove the in vivo metabolism from THC to both 8beta-hydroxy-THC and 8beta,11-dihydroxy-THC in detectable concentrations. The quantitative comparison of 8beta-hydroxy-THC and 8beta,11-dihydroxy-THC with the main cannabinoids THC, 11-hydroxy-THC, and 11-nor-9-carboxy-THC revealed no further informative value for 8beta-hydroxy-THC regarding the last time of cannabis consumption. However, the detectability from 8beta,11-dihydroxy-THC compared to 11-hydroxy-THC suggests a shorter detection time for 8beta,11 dihydroxy-THC and thereby a promising application of this metabolite as a blood marker of recent cannabis use. PMID- 28983688 TI - Inflammatory bowel disease in patients with Hirschsprung's disease: a systematic review and meta-analysis. AB - AIM AND OBJECTIVES: Hirschsprung-associated enterocolitis (HAEC) continues to be an important cause of morbidity in patients with Hirschsprung's disease (HSCR). HAEC can occur at any time during the course of the disease. The reported incidence of HAEC before surgery ranges from 6 to 50%, and after surgery, it ranges from 2 to 35%. HAEC and inflammatory bowel disease (IBD) have similar clinical presentation including diarrhea, hematochezia, and abdominal pain. In recent years, isolated cases of IBD have been reported in patients who had surgical treatment for HSCR. The exact pathogenesis of HAEC or IBD is not known. However, both conditions are characterized by an abnormal intestinal mucosal barrier function, which may be a common pathway. The purpose of this meta analysis was to determine the clinical presentation and outcome in patients with HSCR who developed IBD after pull-through operation. MATERIALS AND METHODS: A systematic literature search for relevant articles was performed in four databases using the combinations of the following terms "inflammatory bowel disease", "Crohn/Crohn's disease", "ulcerative colitis", and "Hirschsprung disease/Hirschsprung's disease" for studies published between 1990 and 2017. The relevant cohorts of HSCR associated with IBD were systematically searched for clinical presentation and outcomes. RESULTS: 14 studies met defined inclusion criteria, reporting a total of 66 patients who had HSCR associated with IBD. Mean age at first operation for HSCR was 5.8 months, mean age at diagnosis of IBD was 7.7 years, and the majority of patients were male (73%). The extent of aganglionosis was total colonic aganglionosis in 41% of patients, long segment in 45%, and rectosigmoid in 14%. The majority of patients underwent a Duhamel procedure (84%) for HSCR. The distribution of IBD was Crohn's disease in 72.3% of patients, ulcerative colitis in 16.9%, and others in 10.8%. Eight articles (47 patients) reported about HAEC, and 22 patients (47%) had experienced HAEC after surgery for HSCR. CONCLUSION: Male patients with extensive colonic aganglionosis who continue to suffer from postoperative HAEC after a Duhamel procedure are more susceptible to develop IBD. Recognition of IBD may be important in the long-term follow-up of HSCR patients who have had postoperative HAEC. PMID- 28983689 TI - Is the answer just beneath the surface? And other updates on recent autonomic research. PMID- 28983687 TI - Low-power laser irradiation inhibits PDGF-BB-induced migration and proliferation via apoptotic cell death in vascular smooth muscle cells. AB - Vascular restenosis after injury of blood vessel has been implicated in various responses including apoptosis, migration, and proliferation in vascular smooth muscle cells (VSMCs) stimulated by diverse growth factors underlying platelet derived growth factor (PDGF). Previous studies evaluated the effects of low-power laser (LPL) irradiation over various wavelength ranges on VSMC events in normal and pathologic states. However, whether VSMC responses are affected by LPL irradiation remains unclear. The purpose of this study is to explore the effects of LPL (green diode laser 532-nm pulsed wave of 300 mW at a spot diameter of 1 mm) irradiation on the responses, apoptosis, migration, and proliferation of VSMCs. The effect of LPL irradiation was tested on VSMCs through cytotoxicity, proliferation, migration, and apoptotic assays. Aortic ring assay was used to assess the effect of LPL irradiation on aortic sprout outgrowth. Protein expression levels were determined by western blotting. LPL irradiation did not affect VSMC viability but slightly attenuated PDGF-BB-induced proliferation in VSMCs. In addition, LPL irradiation inhibited PDGF-BB-evoked migration of VSMCs. Aortic sprout outgrowth in response to PDGF-BB was diminished in cells treated with LPL. In contrast, LPL irradiation evoked apoptosis in VSMCs in the presence of PDGF-BB. Similarly, activation of caspase-3 and Bax, as well as p38 mitogen activated protein kinase (MAPK), in VSMCs treated with PDGF-BB was enhanced by exposure to LPL. These findings indicate that LPL irradiation induces vascular apoptosis via p38 MAPK activation and simultaneously inhibits VSMC proliferation and migration in response to PDGF-BB. PMID- 28983691 TI - Hirschsprung's disease in the laparoscopic transanal pull-through era: implications of age at surgery and technical aspects. AB - AIM: Detailed implications of age at laparoscopic transanal pull-through (LTAPT) on postoperative bowel function (POBF) in Hirschsprung's disease (HD) are somewhat obscure because of a spectrum of factors. METHODS: Age at surgery was used to categorize 106 consecutive postoperative HD cases treated by our modified LTAPT (JLTPAT) between 1997 and 2015; group A: < 3 months old (n = 31); group B: 3-11 months old (n = 44); group C: 1-3 years old (n = 19); and group D: >= 4 years old (n = 12). POBF was assessed by reviewing outpatient records 1, 3, 5, 7, and 10 years after JLTAPT prospectively and scoring each of 5 criteria on a scale of 0-2; best score = 10. RESULTS: Only operative time was statistically longer in group D versus groups A, B, and C. Differences in gender ratios, blood loss, duration of follow-up, and POBF scores were not statistically significant. Mean POBF scores over time were: group A: 6.8, 7.6, 8.4, 8.6, and 8.4; group B: 7.1, 7.8, 8.3, 8.5, and 9.0; group C: 6.9, 7.9, 8.1, 8.3, and 8.6; group D: 7.0, 7.4, 8.2, 8.1, and 8.5, respectively. CONCLUSION: Age at JLTAPT was not correlated with POBF in HD. PMID- 28983690 TI - Subcellular localization and characterization of estrogenic pathway regulators and mediators in Atlantic salmon spermatozoal cells. AB - Much progress has been made regarding our understanding of aromatase regulation, estrogen synthesis partitioning and communication between the germinal and somatic compartments of the differentiating gonad. We now know that most of the enzymatic and signaling apparatus required for steroidogenesis is endogenously expressed within germ cells. However, less is known about the expression and localization of steroidogenic components within mature spermatozoa. We have assembled a sperm library presenting 197,015 putative transcripts. Co-expression clustering analysis revealed that 6687 genes were present at higher levels in sperm in comparison to fifteen other salmon tissue libraries. The sperm transcriptome is highly complex containing the highest proportion of unannotated genes (45%) of the tissues analyzed. Our analysis of highly expressed genes in late-stage sperm revealed dedication to tasks involving chromatin remodeling, flagellogenesis and proteolysis. In addition, using various different embedding and microscopic techniques, we examined the morphology of salmon spermatozoa and characterized expression and localization of several estrogenic regulatory and signaling proteins by immunohistochemistry. We provide evidence for the endogenous synthesis and localization of aromatase (CYP19A and CYP19B1) and potential mediators of estrogen [i.e., ER-alpha and soluble adenylyl cyclase (sAC)] or phosphate (i.e., CREB and FOXL2A) signaling. Partitioning of select transcripts that encode AR-beta, FSH and the LH receptor, but not AR-alpha, LH or the FSH receptor, further points to localized specificity of function in the steroidogenic circuitry of the sperm cell. These results open new avenues of investigation to further our understanding of the intra- and intercellular regulatory processes that guide sperm development and biology. PMID- 28983692 TI - Roseomonas aeriglobus sp. nov., isolated from an air-conditioning system. AB - A novel pale pink-coloured, strictly aerobic, Gram-stain negative bacterial strain, designated strain KER25-12T, was isolated from a laboratory air conditioning system in South Korea. Cells were observed to be non-motile cocci showing positive catalase and oxidase reactions. Strain KER25-12T was found to grow at 10-30 degrees C (optimum, 25-30 degrees C), at pH 4.0-9.0 (optimum, pH 6.0-7.0) and in the presence of 0-2% (w/v) NaCl (optimum, 0%). Ubiquinone-10 and spermidine were detected as the sole respiratory quinone and the predominant polyamine, respectively. The major fatty acids were identified as summed feature 8 (comprising C18:1 omega7c and/or C18:1 omega6c), summed feature 3 (comprising C16:1 omega7c and/or C16:1 omega6c), C16:0 and C18:0. The genomic DNA G+C content of strain KER25-12T was determined to be 70.0 mol%. The major polar lipids were identified as diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine and an unidentified aminolipid. Phylogenetic analysis based on 16S rRNA gene sequence comparison revealed that strain KER25-12T belongs to the genus Roseomonas and shows high sequence similarity to Roseomonas aerilata 5420S-30T (98.57%), Roseomonas pecuniae N75T (97.44%) and Roseomonas vinacea CPCC 100056T (97.40%). Based on the morphological, physiological, chemotaxonomic and phylogenetic features, strain KER25-12T is concluded to represent a novel species of the genus Roseomonas, for which the name Roseomonas aeriglobus sp. nov. is proposed. The type strain is KER25-12T (= KACC 19282T = JCM 32049T). PMID- 28983693 TI - Random non-fasting C-peptide testing can identify patients with insulin-treated type 2 diabetes at high risk of hypoglycaemia. AB - AIMS/HYPOTHESIS: The aim of this study was to determine whether random non fasting C-peptide (rCP) measurement can be used to assess hypoglycaemia risk in insulin-treated type 2 diabetes. METHODS: We compared continuous glucose monitoring-assessed SD of blood glucose and hypoglycaemia duration in 17 patients with insulin-treated type 2 diabetes and severe insulin deficiency (rCP < 200 pmol/l) and 17 matched insulin-treated control patients with type 2 diabetes but who had preserved endogenous insulin (rCP > 600 pmol/l). We then assessed the relationship between rCP and questionnaire-based measures of hypoglycaemia in 256 patients with insulin-treated type 2 diabetes and a comparison group of 209 individuals with type 1 diabetes. RESULTS: Continuous glucose monitoring (CGM) assessed glucose variability and hypoglycaemia was greater in individuals with rCP < 200 pmol/l despite similar mean glucose. In those with low vs high C peptide, SD of glucose was 4.2 (95% CI 3.7, 4.6) vs 3.0 (2.6, 3.4) mmol/l (p < 0.001). In the low-C-peptide vs high-C-peptide group, the proportion of individuals experiencing sustained hypoglycaemia <= 4 mmol/l was 94% vs 41% (p < 0.001), the mean rate of hypoglycaemia was 5.5 (4.4, 6.7) vs 2.1 (1.4, 2.9) episodes per person per week (p = 0.004) and the mean duration was 630 (619, 643) vs 223 (216, 230) min per person per week (p = 0.01). Hypoglycaemia <= 3 mmol/l was infrequent in individuals with preserved C-peptide (1.8 [1.2, 2.6] episodes per person per week vs 0.4 [0.1, 0.8] episodes per person per week for low vs high C-peptide, p = 0.04) and only occurred at night. In a population-based cohort with insulin-treated type 2 diabetes, self-reported hypoglycaemia was twice as frequent in those with rCP < 200 pmol/l (OR 2.0, p < 0.001) and the rate of episodes resulting in loss of consciousness or seizure was five times higher (OR 5.0, p = 0.001). The relationship between self-reported hypoglycaemia and C peptide was similar in individuals with type 1 and type 2 diabetes. CONCLUSIONS/INTERPRETATION: Low rCP is associated with increased glucose variability and hypoglycaemia in patients with insulin-treated type 2 diabetes and represents a practical, stable and inexpensive biomarker for assessment of hypoglycaemia risk. PMID- 28983694 TI - Incomplete vaccination coverage in European children with end-stage kidney disease prior to renal transplantation. AB - BACKGROUND: Because infections constitute a major cause of morbidity and mortality in paediatric renal allograft recipients, avoidance of preventable systemic infections by vaccination before transplantation is of utmost importance. However, data on the completeness of vaccinations and factors associated with incomplete vaccination coverage are scarce. METHODS: Within the framework of the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN), we therefore performed a multi-centre, multi-national, retrospective study investigating the vaccination coverage before transplantation of 254 European children with end-stage renal disease (mean age 10.0 +/- 5.6 years). RESULTS: Only 22 out of 254 patients (8.7%) presented complete vaccination coverage. In particular, the respective vaccination coverage against human papillomavirus (27.3%), pneumococci (42.0%), and meningococci (47.9%) was low. Patients with complete pneumococcal vaccination coverage had numerically less lower respiratory tract infections during the first 3 years post-transplant than children without vaccination or with an incomplete status (16.4% vs 27.7%, p = 0.081). Vaccine-preventable diseases post-transplant were 4.0 times more frequently in unvaccinated than in vaccinated patients. Factors associated with an incomplete vaccination coverage were non-Caucasian ethnicity (OR 9.21, p = 0.004), chronic dialysis treatment before transplantation (OR 6.18, p = 0.001), and older age at transplantation (OR 1.33, p < 0.001). CONCLUSIONS: The vaccination coverage in paediatric kidney transplant candidates is incomplete. Paediatric nephrologists, together with primary-care staff and patients' families, should therefore make every effort to improve vaccination rates before kidney transplantation. PMID- 28983695 TI - Signal reduction in choriocapillaris and segmentation errors in spectral domain OCT angiography caused by soft drusen. AB - PURPOSE: To analyze signal reduction in choriocapillaris (CC) and segmentation errors in spectral domain optical coherence tomography angiography (OCT-A) caused by soft drusen due to age-related macular degeneration (AMD). METHODS: Twenty four eyes of 24 patients underwent multimodal retinal imaging including central 3 * 3mm2 OCT-A (AngioVue, Optovue). Three drusen per study eye were randomly chosen and evaluated regarding drusen height, diameter, and accuracy of OCT-A layer segmentation in lesion proximity. Structural en-face OCT CC images were graded qualitatively and quantitatively regarding signal loss underneath the individual drusen area. Those drusen that showed no distinct signal loss in structural en face OCT CC images were further evaluated in OCT-A. CC decorrelation signal index was measured within a 30-MUm OCT-A CC slab in the exact area of drusen affection. Data were compared to healthy age-matched control subjects. Accuracy of layer segmentation, OCT CC data, and OCT-A CC data were correlated to morphological drusen parameters. RESULTS: Mean drusen height and diameter were 91.57 +/- 19.5MUm and 315.17 +/- 116.7MUm. OCT-A layer segmentation of the inner plexiform layer (IPL) was disturbed by more than 50 MUm in proximity to 26 drusen (36.1%). In these patients, drusen height was significantly higher compared to those with accurate IPL segmentation (p = 0.0126). Sixty-six out of 72 drusen (91.7%) caused a distinct signal loss in the structural en-face OCT CC image. Drusen height and drusen diameter were significantly higher in this group compared to the six drusen with a sufficient signal (p = 0.0276, p = 0.0025). CC decorrelation signal index measured in the area of these six drusen without OCT signal loss (8.3%) was reduced compared to age-matched healthy controls (73.6 vs. 100.1; p = 0.001). CONCLUSIONS: Signal attenuation in CC slabs and segmentation errors of the IPL depend on drusen morphology. Both are frequent artifacts in OCT-A imaging in patients with soft drusen and must be considered during image analysis. PMID- 28983696 TI - Is the eCura system useful for selecting patients who require radical surgery after noncurative endoscopic submucosal dissection for early gastric cancer? A comparative study. AB - BACKGROUND: We have established a risk-scoring system, termed the "eCura system," for the risk stratification of lymph node metastasis in patients who have received noncurative endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). We aimed to clarify whether this system contributes to the selection of patients requiring radical surgery after ESD. METHODS: Between 2000 and 2011, 1,969 patients with noncurative ESD for EGC were included in this multicenter study. Depending on the treatment strategy after ESD, we had patients with no additional treatment (n = 905) and those with radical surgery after ESD (n = 1,064). After the application of the eCura system to these patients, cancer recurrence and cancer-specific mortality in each risk category of the system were compared between the two patient groups. RESULTS: Multivariate Cox analysis revealed that in the high-risk category, cancer recurrence was significantly higher (hazard ratio = 3.13, p = 0.024) and cancer-specific mortality tended to be higher (hazard ratio = 2.66, p = 0.063) in patients with no additional treatment than in those with radical surgery after ESD, whereas no significant differences were observed in the intermediate-risk and low-risk categories. In addition, cancer-specific survival in the low-risk category was high in both patient groups (99.6 and 99.7%). A limitation of this study is that it included a small number of cases with undifferentiated-type EGC (292 cases). CONCLUSIONS: The eCura system is a useful aid for selecting the appropriate treatment strategy after noncurative ESD for EGC. However, caution is needed when applying this system to patients with undifferentiated-type EGC. PMID- 28983697 TI - Screening for biliary atresia. AB - Early diagnosis followed by proper KP is essential for the improvement of long term prognosis for patients with BA. It is increasingly accepted that KP at <= 30 days of age significantly improves native liver survival rate. Published analyses in English and Japanese indicate that screening by SCC and DB/CB is potentially feasible. Screening with SCC has been implemented in Tochigi Prefecture, Japan, since 1994. The concept of SCC was introduced from Japan to Taiwan and resulted in nationwide screening with SCC for the first time in Taiwan in 2004, followed by Japan in 2012. Home-based screening using SCC is easy and cost-effective; however, it may cause some difficulties for families in case of stools with intermediate colors. Laboratory-based screening using DB/CB may detect the suspected cases earlier, resulting in an increase in the number of patients with BA who undergo KP at <= 30 days of age; however, the recall rate is 1% and may be beyond an acceptable range. Further studies are needed to assess the feasibility and cost-effectiveness of both home-based (SCC) and laboratory-based (DB/CB) screening for BA. PMID- 28983698 TI - Pathogenic characteristics of a novel intranuclear coccidia in Japanese black calves and its genetic identification as Eimeria subspherica. AB - Bovine intranuclear coccidiosis is caused by the protozoans Eimeria alabamensis and Cyclospora spp. Here, we characterized the disease and genetically identified the causative species in Japanese black calves with chronic and refractory watery diarrhea. Histologic examinations revealed atrophy of the jejunal villi and numerous parasites in the nucleus of epithelial cells in the jejunum. Based on molecular analyses using 18S ribosomal RNA gene-specific primers that we designed, the parasites were found to be formed in the same cluster as Eimeria subspherica in the phylogenetic tree, which was separated from those of other related Eimeria spp. These results constitute the first report of E. subspherica as a cause of bovine intranuclear coccidiosis. PMID- 28983699 TI - Teriparatide rapidly improves pain-like behavior in ovariectomized mice in association with the downregulation of inflammatory cytokine expression. AB - Recent studies have indicated that teriparatide, an anti-osteoporosis agent, significantly improves back pain regardless of the presence of vertebral fracture in osteoporosis patients. The aims of this study were to examine whether teriparatide improves pain-like behavior in an ovariectomized (OVX) mouse model, and to evaluate changes in osteoclast marker levels and inflammatory cytokine expression levels induced by teriparatide treatment in bone tissue in association with improvements in pain-like behavior. OVX and sham operations were performed in 8-week-old mice, followed by teriparatide treatment for 2 weeks. Pain-like behavior tests (von Frey, paw flick and spontaneous pain test), and the measurement of serum tartrate-resistant acid phosphatase 5b (TRAP5b) level and inflammatory cytokine (interleukin [IL]-1beta, IL-6 and tumor necrosis factor [TNF]-alpha) expression levels in the bone tissue were conducted after teriparatide treatment in OVX mice. Pain-like behavior in the von Frey test was significantly improved by teriparatide treatment in OVX mice. With regard to the early phase (within the first 7 days of treatment), teriparatide significantly improved pain-like behavior in the von Frey test, the paw flick test and the spontaneous pain test. Teriparatide significantly inhibited the expression of IL 1beta, IL-6 and TNF-alpha in OVX mice in the early phase of the treatment, while the TRAP5b level in OVX mice was not significantly affected. We demonstrated that the teriparatide-induced rapid improvement effect on pain-like behavior in OVX mice was associated with the downregulation of inflammatory cytokine expression, including IL-1beta, IL-6 and TNF-alpha. PMID- 28983701 TI - Reduced H3K27me3 expression in radiation-associated angiosarcoma of the breast. AB - The diagnosis of radiation-associated angiosarcoma is challenging and there are overlapping clinicopathological features between radiation-associated benign, atypical and malignant vascular lesions. It has been shown convincingly, that the majority of radiation-associated angiosarcomas are characterised by amplification and subsequent overexpression of MYC in contrast to benign and atypical vascular lesions. Given the fact that epigenetic changes play an important role in carcinogenesis and loss of histone H3K27 trimethylation (H3K27me3) has been found in a number of malignant neoplasms including malignant peripheral nerve sheath tumours, especially when associated with previous radiotherapy, we evaluated the immunohistochemical reaction pattern for H3K27me3 in 49 vascular lesions and control cases: normal skin and benign vascular lesions not associated with previous radiotherapy, radiation-associated benign, atypical and malignant vascular lesions and angiosarcomas not associated with previous radiotherapy. We found loss of H3K27me3 expression in most cases of radiation-associated angiosarcomas, whereas endothelial cells in benign and atypical vascular lesions arising after previous radiotherapy stained positively for H3K27me3. The sporadic angiosarcomas stained inconsistently for H3K27me3. Loss of H3K27me3 is typically seen in radiation-associated angiosarcomas, representing an additional diagnostic tool and raises questions in regard to the carcinogenesis of malignant vascular neoplasms. PMID- 28983702 TI - Measurement of the 15N/14N ratio of phenylalanine in fermentation matrix by isotope ratio mass spectrometry. AB - OBJECTIVES: To determine the origin of 15N-labeled phenylalanine in microbial metabolic flux analysis using 15N as a tracer, a method for measuring phenylalanine delta15N using HPLC coupled with elemental analysis-isotope ratio mass spectrometry (EA-IRMS) was developed. RESULTS: The original source of the 15N-labeled phenylalanine was determined using this new method that consists of three steps: optimization of the HPLC conditions, evaluation of the isotope fractionation effects, and evaluation of the effect of pre-processing on the phenylalanine nitrogen stable isotope. In addition, the use of a 15N-labeled inorganic nitrogen source, rather than 15N-labeled amino acids, was explored using this method. CONCLUSIONS: The method described here can also be applied to the analysis of metabolic flux. PMID- 28983703 TI - Mapping Slow Waves by EEG Topography and Source Localization: Effects of Sleep Deprivation. AB - Slow waves are a salient feature of the electroencephalogram (EEG) during non rapid eye movement (non-REM) sleep. The aim of this study was to assess the topography of EEG power and the activation of brain structures during slow wave sleep under normal conditions and after sleep deprivation. Sleep EEG recordings during baseline and recovery sleep after 40 h of sustained wakefulness were analyzed (eight healthy young men, 27 channel EEG). Power maps were computed for the first non-REM sleep episode (where sleep pressure is highest) in baseline and recovery sleep, at frequencies between 0.5 and 2 Hz. Power maps had a frontal predominance at all frequencies between 0.5 and 2 Hz. An additional occipital focus of activity was observed below 1 Hz. Power maps <= 1 Hz were not affected by sleep deprivation, whereas an increase in power was observed in the maps >= 1.25 Hz. Based on the response to sleep deprivation, low-delta (0.5-1 Hz) and mid delta activity (1.25-2 Hz) were dissociated. Electrical sources within the cortex of low- and mid-delta activity were estimated using eLORETA. Source localization revealed a predominantly frontal distribution of activity for low-delta and mid delta activity. Sleep deprivation resulted in an increase in source strength only for mid-delta activity, mainly in parietal and frontal regions. Low-delta activity dominated in occipital and temporal regions and mid-delta activity in limbic and frontal regions independent of the level of sleep pressure. Both, power maps and electrical sources exhibited trait-like aspects. PMID- 28983704 TI - Presentation of pediatric Henoch-Schonlein purpura nephritis changes with age and renal histology depends on biopsy timing. AB - BACKGROUND: This study correlates the clinical presentation of Henoch-Schonlein purpura nephritis (HSPN) with findings on initial renal biopsy. METHODS: Data from 202 pediatric patients enrolled in the HSPN registry of the German Society of Pediatric Nephrology reported by 26 centers between 2008 and 2014 were analyzed. All biopsy reports were re-evaluated for the presence of cellular crescents or chronic pathological lesions (fibrous crescents, glomerular sclerosis, tubular atrophy >5%, and interstitial fibrosis >5%). RESULTS: Patients with HSPN with cellular glomerular crescents were biopsied earlier after onset of nephritis (median 24 vs 36 days, p = 0.04) than those without, whereas patients with chronic lesions were biopsied later (57 vs 19 days, p < 0.001) and were older (10.3 vs 8.6 years, p = 0.01) than those without. Patients biopsied more than 30 days after the onset of HSPN had significantly more chronic lesions (52 vs 22%, p < 0.001), lower eGFR (88 vs 102 ml/min/1.73m2, p = 0.01), but lower proteinuria (2.3 vs 4.5 g/g, p < 0.0001) than patients biopsied earlier. Children above 10 years of age had lower proteinuria (1.98 vs 4.58 g/g, p < 0.001), lower eGFR (86 vs 101 ml/min/1.73m2, p = 0.002) and were biopsied significantly later after onset of nephritis (44 vs 22 days, p < 0.001) showing more chronic lesions (45 vs 30%, p = 0.03). Proteinuria and renal function at presentation decreased with age. CONCLUSIONS: In summary, we find an age-dependent presentation of HSPN with a more insidious onset of non-nephrotic proteinuria, impaired renal function, longer delay to biopsy, and more chronic histopathological lesions in children above the age of 10 years. Thus, HSPN presents more like Immunoglobulin A (IgA) nephritis in older than in younger children. PMID- 28983706 TI - Validation of 3D documentation of palatal soft tissue shape, color, and irregularity with intraoral scanning. AB - OBJECTIVES: The purpose of this study was to assess the feasibility of 3D intraoral scanning for documentation of palatal soft tissue by evaluating the accuracy of shape, color, and curvature. MATERIALS AND METHODS: Intraoral scans of ten participants' upper dentition and palate were acquired with the TRIOS(r) 3D intraoral scanner by two observers. Conventional impressions were taken and digitized as a gold standard. The resulting surface models were aligned using an Iterative Closest Point approach. The absolute distance measurements between the intraoral models and the digitized impression were used to quantify the trueness and precision of intraoral scanning. The mean color of the palatal soft tissue was extracted in HSV (hue, saturation, value) format to establish the color precision. Finally, the mean curvature of the surface models was calculated and used for surface irregularity. RESULTS: Mean average distance error between the conventional impression models and the intraoral models was 0.02 +/- 0.07 mm (p = 0.30). Mean interobserver color difference was - 0.08 +/- 1.49 degrees (p = 0.864), 0.28 +/- 0.78% (p = 0.286), and 0.30 +/- 1.14% (p = 0.426) for respectively hue, saturation, and value. The interobserver differences for overall and maximum surface irregularity were 0.01 +/- 0.03 and 0.00 +/- 0.05 mm. CONCLUSIONS: This study supports the hypothesis that the intraoral scan can perform a 3D documentation of palatal soft tissue in terms of shape, color, and curvature. CLINICAL RELEVANCE: An intraoral scanner can be an objective tool, adjunctive to the clinical examination of the palatal tissue. PMID- 28983705 TI - Comparative adherence to weekly oral and quarterly intravenous bisphosphonates among patients with limited heath literacy who sustained distal radius fractures. AB - Individuals with limited health literacy (HL) are less likely to obtain preventive care. We designed a study to compare adherence to weekly oral and quarterly intravenous bisphosphonates among patients with low HL. The study enrolled a total of 432 female patients who presented with a distal radius fracture caused by low-energy trauma. Participant HL was measured using the Newest Vital Sign tool, and patients were randomized to weekly oral or quarterly intravenous bisphosphonate groups. Subjects in the intravenous bisphosphonate group received intravenous injections of 3 mg ibandronate every 3 months, and those in the oral bisphosphonate group self-administered 70 mg alendronate orally once each week for 12 months. The adherence to weekly oral or quarterly intravenous bisphosphonates was analyzed by HL level. The rate of adherence to quarterly intravenous bisphosphonates was significantly higher than that for weekly oral bisphosphonates in patients with inadequate HL (73 vs. 46%, p = 0.001), whereas no significant differences were observed between HL groups in adherence to intravenous bisphosphonate. Conversely, the rate of adherence to orally administered bisphosphonates was significantly lower in patients with inadequate HL than in those with appropriate HL (46 vs. 65%, p = 0.005). After controlling for confounding variables, inadequate HL, the presence of comorbidities, and weekly oral bisphosphonates were associated with a higher likelihood of nonadherence to osteoporosis treatment. Thus patients with limited health literacy can achieve rates of adherence to quarterly intravenous bisphosphonates, as opposed to weekly oral bisphosphonates, similar to rates among patients with appropriate literacy. PMID- 28983707 TI - Clinical and Radiological Discrimination of Solitary Pulmonary Lesions in Colorectal Cancer Patients. AB - OBJECTIVES: The lung is one of the most common organs of metastasis from colorectal cancer (CRC), and we have encountered lung cancer patients with a history of CRC. There have been few studies regarding methods used to discriminate between primary lung cancer (PLC) and pulmonary metastasis from CRC (PM-CRC) based only on preoperative findings. We retrospectively investigated predictive factors discriminating between these lesions in patients with a history of CRC. METHODS: Between 2006 and 2015, 117 patients with a history of CRC (44 patients with 47 PLC and 73 patients with 102 PM-CRC) underwent subsequent or concurrent resection of pulmonary lesions. We compared the clinical and radiological characteristics of 100 patients with solitary lesions (43 PLC and 57 PM-CRC). Using univariate and multivariate analyses, we examined predictive factors for discrimination of these two lesions. RESULTS: All tumors with findings of ground-glass opacity (GGO) were PLC (n = 19). In a multivariate analysis of 81 radiologically solid tumors, two factors were found to be significant independent predictors of PLC: a history of stage I CRC and presence of pleural indentation. All tumors in 26 patients with either GGO or both a stage I CRC history and pleural indentation were PLC, while most tumors in patients without all three factors were PM-CRC (43/44; 97.7%). CONCLUSIONS: The presence or absence of GGO, pathological CRC stage, and pleural indentation could be useful factors to distinguish between PLC and PM-CRC. PMID- 28983708 TI - Screening children for hypertension: the case against. PMID- 28983709 TI - Late complications of biliary atresia: hepatopulmonary syndrome and portopulmonary hypertension. AB - Children with biliary atresia (BA) following Kasai portoenterostomy have a high risk for portal hypertension, however, while variceal and hemorrhagic complications have been more commonly studied, less frequent but no less possibly devastating complications of hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PPH) remain less well understood. HPS and PPH both occur in a setting of portal hypertension, however, paradoxically patients with HPS develop pulmonic vasculature dilation leading to shunting and hypoxia, while those with PPH develop an opposite progression of pulmonary vasoconstriction eventually leading to cor pulmonale and decompensation. Given the near diametric evolution of diseases, HPS and PPH differ widely in therapy, though liver transplantation can have a role for treatment in either disease state. We reviewed our series of 320 pediatric patients with biliary atresia treated at our institution over 44 years, highlighting two cases that developed HPS and PPH, respectively, using these cases in further discussion of hepatopulmonary syndrome and portopulmonary hypertension regarding disease etiology, diagnosis, management, and prognosis. The complicated nature of these processes demand a careful multidisciplinary approach to optimize patient outcomes, including mindful evaluation for when transplantation may offer benefit. PMID- 28983711 TI - Economic and disease burden of breast cancer associated with suboptimal breastfeeding practices in Mexico. AB - PURPOSE: Exclusive breastfeeding and longer breastfeeding reduce women's breast cancer risk but Mexico has one of the lowest breastfeeding rates worldwide. We estimated the lifetime economic and disease burden of breast cancer in Mexico if 95% of parous women breastfeed each child exclusively for 6 months and continue breastfeeding for over a year. METHODS: We used a static microsimulation model with a cost-of-illness approach to simulate a cohort of Mexican women. We estimated breast cancer incidence, premature mortality, disability-adjusted life years (DALYs), medical costs, and income losses due to breast cancer and extrapolated the results to 1.116 million Mexican women of age 15 in 2012. Costs were expressed in 2015 US dollars and discounted at a 3% annual rate. RESULTS: We estimated that 2,186 premature deaths (95% CI 2,123-2,248), 9,936 breast cancer cases (95% CI 9,651-10,220), 45,109 DALYs (95% CI 43,000-47,217), and $245 million USD (95% CI 234-256) in medical costs and income losses owing to breast cancer could be saved over a cohort's lifetime. Medical costs account for 80% of the economic burden; income losses and opportunity costs for caregivers account for 15 and 5%, respectively. CONCLUSIONS: In Mexico, the burden of breast cancer due to suboptimal breastfeeding in women is high in terms of morbidity, premature mortality, and the economic costs for the health sector and society. PMID- 28983712 TI - ARHGAP18 is a novel gene under positive natural selection that influences HbF levels in beta-thalassaemia. AB - Foetal haemoglobin (HbF) plays a dominant role in ameliorating the morbidity and mortality of beta-thalassaemia. A better understanding of the loci and genes involved in HbF expression would be beneficial for the treatment of beta thalassaemia major. However, the genes associated with HbF expression remain largely unknown. In this study, we first explored large-scale data sets and examined the human genome for evidence of positive natural selection to screen out single nucleotide polymorphisms (SNPs). A genetic analysis of HbF levels was conducted in a Chinese cohort of patients with beta-thalassaemia to confirm the bioinformatics results. A total of 1141 subjects with beta-thalassaemia were recruited. The results showed that the SNP rs11759328 in the ARHGAP18 gene was significantly associated with HbF levels (Rho = 5.1 * 10-4). ARHGAP18 belongs to the RhoGAP family and controls angiogenesis, cellular morphology and motility. Second, after determining that ARHGAP18 was highly expressed in the human K562 cell line, we used lentiviral-mediated small interfering RNA to knock down ARHGAP18 expression and subsequently assessed cell proliferation and apoptosis using cell proliferation assays and flow cytometry, respectively. ARHGAP18 downregulation in K562 cells significantly increased HBG1/2 expression and apoptosis, but proliferation was not significantly affected in vitro. Our data suggest that ARHGAP18, which was located by the SNP rs11759328 via positive selection, plays a potential role in regulating HbF expression in beta thalassaemia and may be a promising therapeutic target. Knockout studies of ARHGAP18 warrant further investigation into its aetiology in HbF. PMID- 28983715 TI - Father's Role in Preconception Health. AB - As part of the federal multi-agency conference on Paternal Involvement in Pregnancy Outcomes, the existing Fatherhood paradigm was expanded to include a new focus on Men's Preconception Health. This concept grew out of the women's preconception health movement and the maternal and child health (MCH) life course perspective, as well as pioneering research from the child development, public health data and family planning fields. It encourages a new examination of how men's preconception health impacts both reproductive outcomes and men's own subsequent health and development. This essay introduces the concept of men's preconception health and health care; examines its historical development; notes the challenges of its inclusion into fatherhood and reproductive health programs; and situates it within a longer men's reproductive health life course. We then briefly explore six ways men's preconception health and health care can have positive direct and indirect impacts-planned and wanted pregnancies (family planning); enhanced paternal biologic and genetic contributions; improved reproductive health biology for women; improved reproductive health practices and outcomes for women; improved capacity for parenthood and fatherhood (psychological development); and enhanced male health through access to primary health care. Research on men's preconception health and health care is very limited and siloed. We propose a research agenda to advance this topic in three broad domains: increasing the basic epidemiology and risk factor knowledge base; implementing and evaluating men's preconception health/fatherhood interventions (addressing clinical health care, psychological resiliency/maturation, and social determinants of health); and fostering more fatherhood health policy and advocacy research. PMID- 28983714 TI - A Novel Phenylchromane Derivative Increases the Rate of Glucose Uptake in L6 Myotubes and Augments Insulin Secretion from Pancreatic Beta-Cells by Activating AMPK. AB - PURPOSE: A series of novel polycyclic aromatic compounds that augment the rate of glucose uptake in L6 myotubes and increase glucose-stimulated insulin secretion from beta-cells were synthesized. Designing these molecules, we have aimed at the two main pathogenic mechanisms of T2D, deficient insulin secretion and diminished glucose clearance. The ultimate purpose of this work was to create a novel antidiabetic drug candidate with bi-functional mode of action. METHODS: All presented compounds were synthesized, and characterized in house. INS-1E cells and L6 myoblasts were used for the experiments. The rate of glucose uptake, mechanism of action, level of insulin secretion and the druggability of the lead compound were studied. RESULTS: The lead compound (6-(1,3-dithiepan-2-yl)-2 phenylchromane), dose- and time-dependently at the low MUM range increased the rate of glucose uptake in L6 myotubes and insulin secretion in INS-1E cells. The compound exerted its effects through the activation of the LKB1 (Liver Kinase B1) AMPK pathway. In vitro metabolic parameters of this lead compound exhibited good druggability. CONCLUSIONS: We anticipate that bi-functionality (increased rate of glucose uptake and augmented insulin secretion) will allow the lead compound to be a starting point for the development of a novel class of antidiabetic drugs. PMID- 28983716 TI - Diagnostic and therapeutic evaluation of multiple choroidal granulomas in a patient with confirmed sarcoidosis using enhanced depth imaging optical coherence tomography. AB - PURPOSE: Sarcoidosis is a major cause of granulomatous uveitis but rarely manifests as multiple choroidal granulomas. This report describes the use of enhanced depth imaging optical coherence tomography (EDI-OCT) to visualize changes occurring in multiple choroidal granulomas during treatment. METHODS: The patient was a 36-year-old Japanese man with histopathologically confirmed sarcoidosis, who was examined using EDI-OCT and showed multiple yellowish-white subretinal lesions in the peripapillary region and the arcade of the right eye. RESULTS: EDI-OCT revealed homogeneous hyporeflective choroidal lesions with choriocapillaris thinning, consistent with a diagnosis of choroidal granulomas. Subretinal fluid adjacent to one of the peripapillary choroidal lesions was also apparent. EDI-OCT during oral prednisolone administration revealed a decrease in lesion size at as early as 3 weeks and complete resolution of the lesions after 6 months of treatment. However, 2 months after prednisolone discontinuation, EDI OCT revealed recurrence of choroidal granulomas in the peripapillary region and the arcade of the right eye. After injection of triamcinolone acetonide into the posterior sub-Tenon's capsule (sub-Tenon's injection), EDI-OCT demonstrated a reduction in granuloma lesion size within 3 months of the injection. CONCLUSION: EDI-OCT allowed detailed morphologic visualization of the choroidal granulomas caused by sarcoidosis. This imaging technique was useful for monitoring changes in granuloma size in response to steroid administration and for early detection of recurrence. Injection of triamcinolone acetonide into the posterior sub Tenon's capsule was as effective as oral prednisolone for the treatment of choroidal granulomas. PMID- 28983713 TI - Baseline and annual repeat rounds of screening: implications for optimal regimens of screening. AB - OBJECTIVES: Differences in results of baseline and subsequent annual repeat rounds provide important information for optimising the regimen of screening. METHODS: A prospective cohort study of 65,374 was reviewed to examine the frequency/percentages of the largest noncalcified nodule (NCN), lung cancer cell types and Kaplan-Meier (K-M) survival rates, separately for baseline and annual rounds. RESULTS: Of 65,374 baseline screenings, NCNs were identified in 28,279 (43.3%); lung cancer in 737 (1.1%). Of 74,482 annual repeat screenings, new NCNs were identified in 4959 (7%); lung cancer in 179 (0.24%). Only adenocarcinoma was diagnosed in subsolid NCNs. Percentages of lung cancers by cell type were significantly different (p < 0.0001) in the baseline round compared with annual rounds, reflecting length bias, as were the ratios, reflecting lead times. Long term K-M survival rate was 100% for typical carcinoids and for adenocarcinomas manifesting as subsolid NCNs; 85% (95% CI 81-89%) for adenocarcinoma, 74% (95% CI 63-85%) for squamous cell, 48% (95% CI 34-62%) for small cell. The rank ordering by lead time was the same as the rank ordering by survival rates. CONCLUSIONS: The significant differences in the frequency of NCNs and frequency and aggressiveness of diagnosed cancers in baseline and annual repeat need to be recognised for an optimal regimen of screening. KEY POINTS: * Lung cancer aggressiveness varies considerably by cell type and nodule consistency. * Kaplan Meier survival rates varied by cell type between 100% and 48%. * The percentages of lung cancers by cell type in screening rounds reflect screening biases. * Rank ordering by cell type survival is consistent with that by lead times. * Empirical evidence provides critical information for the regimen of screening. PMID- 28983717 TI - Economic growth and CO2 emissions: an investigation with smooth transition autoregressive distributed lag models for the 1800-2014 period in the USA. AB - The study aims to combine the autoregressive distributed lag (ARDL) cointegration framework with smooth transition autoregressive (STAR)-type nonlinear econometric models for causal inference. Further, the proposed STAR distributed lag (STARDL) models offer new insights in terms of modeling nonlinearity in the long- and short-run relations between analyzed variables. The STARDL method allows modeling and testing nonlinearity in the short-run and long-run parameters or both in the short- and long-run relations. To this aim, the relation between CO2 emissions and economic growth rates in the USA is investigated for the 1800-2014 period, which is one of the largest data sets available. The proposed hybrid models are the logistic, exponential, and second-order logistic smooth transition autoregressive distributed lag (LSTARDL, ESTARDL, and LSTAR2DL) models combine the STAR framework with nonlinear ARDL-type cointegration to augment the linear ARDL approach with smooth transitional nonlinearity. The proposed models provide a new approach to the relevant econometrics and environmental economics literature. Our results indicated the presence of asymmetric long-run and short run relations between the analyzed variables that are from the GDP towards CO2 emissions. By the use of newly proposed STARDL models, the results are in favor of important differences in terms of the response of CO2 emissions in regimes 1 and 2 for the estimated LSTAR2DL and LSTARDL models. PMID- 28983718 TI - Pediocin-like bacteriocins: new perspectives on mechanism of action and immunity. AB - This review attempts to analyze the mechanism of action and immunity of class IIa bacteriocins. These peptides are promising alternative food preservatives and they have a great potential application in medical sciences. Class IIa bacteriocins act on the cytoplasmic membrane of Gram-positive cells dissipating the transmembrane electrical potential by forming pores. However, their toxicity and immunity mechanism remains elusive. Here we discuss the role of the mannose phosphotransferase system (man-PTS) as the receptor for class IIa bacteriocins and the influence of the membrane composition on the activity of these antimicrobial peptides. A model that is consistent with experimental results obtained by different researchers involves the non-specific binding of the bacteriocin to the negatively charged membrane of target bacteria. This step would facilitate a specific binding to the receptor protein, altering its functionality and forming an independent pore in which the bacteriocin is inserted in the membrane. An immunity protein could specifically recognize and block the pore. Bacteriocins function in bacterial ecosystems and energetic costs associated with their production are also discussed. Theoretical models based on solid experimental evidence are vital to understand bacteriocins mechanism of action and to promote new technological developments. PMID- 28983719 TI - Glucose patterns during an oral glucose tolerance test and associations with future diabetes, cardiovascular disease and all-cause mortality rate. AB - AIMS/HYPOTHESIS: In addition to blood glucose concentrations measured in the fasting state and 2 h after an OGTT, intermediate measures during an OGTT may provide additional information regarding a person's risk of future diabetes and cardiovascular disease (CVD). First, we aimed to characterise heterogeneity of glycaemic patterns based on three time points during an OGTT. Second, we compared the incidences of diabetes and CVD and all-cause mortality rates among those with different patterns. METHODS: Our cohort study included 5861 participants without diabetes at baseline from the Danish Inter99 study. At baseline, all participants underwent an OGTT with measurements of plasma glucose levels at 0, 30 and 120 min. Latent class mixed-effects models were fitted to identify distinct patterns of glycaemic response during the OGTT. Information regarding incident diabetes, CVD and all-cause mortality rates during a median follow-up time of 11, 12 and 13 years, respectively, was extracted from national registers. Cox proportional hazard models with adjustment for several cardiometabolic risk factors were used to compare the risk of diabetes, CVD and all-cause mortality among individuals in the different latent classes. RESULTS: Four distinct glucose patterns during the OGTT were identified. One pattern was characterised by high 30 min but low 2 h glucose values. Participants with this pattern had an increased risk of developing diabetes compared with participants with lower 30 min and 2 h glucose levels (HR 4.1 [95% CI 2.2, 7.6]) and participants with higher 2 h but lower 30 min glucose levels (HR 1.5 [95% CI 1.0, 2.2]). Furthermore, the all-cause mortality rate differed between the groups with significantly higher rates in the two groups with elevated 30 min glucose. Only small non-significant differences in risk of future CVD were observed across latent classes after confounder adjustment. CONCLUSIONS/INTERPRETATION: Elevated 30 min glucose is associated with increased risk of diabetes and all-cause mortality rate independent of fasting and 2 h glucose levels. Therefore, subgroups at high risk may not be revealed when considering only fasting and 2 h glucose levels during an OGTT. PMID- 28983720 TI - Symptomatic and silent cerebral infarction following surgical clipping of unruptured intracranial aneurysms: incidence, risk factors, and clinical outcome. AB - Cerebral infarction (CI) associated with clipping of unruptured intracranial aneurysms (UIAs) has not been completely studied. The role of individual and operative characteristics is not known, and the risk of silent CI has not been well described. To determine the incidence, risk factors, and clinical outcome of postoperative CI, we retrospectively analyzed 388 consecutive patients undergoing clipping of UIAs between January 2012 and December 2015. We reviewed the pre- and postoperative computed tomography (CT) images of each patient. Postoperative CI was defined as a new parenchymal hypodensity in the vascular territory of treated artery. Patient-specific, aneurysm-specific, and operative variables were analyzed as potential risk factors. Functional outcome at discharge was assessed with the modified Rankin Scale (mRS). Postoperative CI was found in 49 (12.6%) patients, 29 of whom manifested neurological deficits. The incidences of symptomatic stroke and silent CI were 7.5 and 5.2%, respectively. Multivariate analysis showed that larger aneurysm size and history of hypertension were significantly associated with CI. Disability (mRS > 2) rate was 42.9% among patients with CI, which was substantially higher than that among patients without (0.9%). In conclusion, the incidence of CI following clipping of UIAs was not low. Larger aneurysm size and history of hypertension were independent risk factors. Postoperative symptomatic stroke correlated with an extremely high risk of disability. Silent CI was seemingly nondisabling, but the possible cognitive consequence is pending. PMID- 28983721 TI - Nutrient limitation of soil microbial activity during the earliest stages of ecosystem development. AB - A dominant paradigm in ecology is that plants are limited by nitrogen (N) during primary succession. Whether generalizable patterns of nutrient limitation are also applicable to metabolically and phylogenetically diverse soil microbial communities, however, is not well understood. We investigated if measures of N and phosphorus (P) pools inform our understanding of the nutrient(s) most limiting to soil microbial community activities during primary succession. We evaluated soil biogeochemical properties and microbial processes using two complementary methodological approaches-a nutrient addition microcosm experiment and extracellular enzyme assays-to assess microbial nutrient limitation across three actively retreating glacial chronosequences. Microbial respiratory responses in the microcosm experiment provided evidence for N, P and N/P co limitation at Easton Glacier, Washington, USA, Puca Glacier, Peru, and Mendenhall Glacier, Alaska, USA, respectively, and patterns of nutrient limitation generally reflected site-level differences in soil nutrient availability. The activities of three key extracellular enzymes known to vary with soil N and P availability developed in broadly similar ways among sites, increasing with succession and consistently correlating with changes in soil total N pools. Together, our findings demonstrate that during the earliest stages of soil development, microbial nutrient limitation and activity generally reflect soil nutrient supply, a result that is broadly consistent with biogeochemical theory. PMID- 28983722 TI - Distributions and sources of heavy metals in sediments of the Bohai Sea, China: a review. AB - This paper summarizes the recent research results from studies concerning heavy metals in the Bohai Sea in recent decades. The temporal and spatial variations and potential sources of the heavy metals in the surface sediments were analyzed. Based on these obtained data, the average concentrations in surface sediments collected in recent years (summarized 3171 samples) were 0.31, 87.0, 25.7, 25.8, 0.11, 16.9, 52.2, and 27.7 MUg/g for Cd, Zn, Cu, Pb, Hg, As, Cr, and Ni, respectively. In the samples collected in the 1980s, the concentrations were 22.6, 21.3, 69.13, 0.26, and 57.5 MUg/g (summarized 218 samples) for Cu, Pb, Zn, Cd, and Cr. The concentrations of Cu, Pb, Zn, and Cd increased slightly. Generally, higher concentrations were measured in the Bohai Bay and central Bohai Sea. The distribution patterns of heavy metals were significantly different between samples collected after the year of 2000 and those in the 1980s. In the 1980s and recent years, higher concentrations of Zn, Cd, and Pb were measured in the samples collected from Bohai Bay and Liaodong Bay, respectively. This indicated that the sources of heavy metals in Bohai Sea were changed significantly during the past decades. PMID- 28983723 TI - Engineering a carotenoid-binding site in Dokdonia sp. PRO95 Na+-translocating rhodopsin by a single amino acid substitution. AB - Light-driven H+, Cl- and Na+ rhodopsin pumps all use a covalently bound retinal molecule to capture light energy. Some H+-pumping rhodopsins (xanthorhodopsins; XRs) additionally contain a carotenoid antenna for light absorption. Comparison of the available primary and tertiary structures of rhodopsins pinpointed a single Thr residue (Thr216) that presumably prevents carotenoid binding to Na+ pumping rhodopsins (NaRs). We replaced this residue in Dokdonia sp. PRO95 NaR with Gly, which is found in the corresponding position in XRs, and produced a variant rhodopsin in a ketocarotenoid-synthesising Escherichia coli strain. Unlike wild-type NaR, the isolated variant protein contained the tightly bound carotenoids canthaxanthin and echinenone. These carotenoids were visible in the absorption, circular dichroism and fluorescence excitation spectra of the Thr216Gly-substituted NaR, which indicates their function as a light-harvesting antenna. The amino acid substitution and the bound carotenoids did not affect the NaR photocycle. Our findings suggest that the antenna function was recently lost during NaR evolution but can be easily restored by site-directed mutagenesis. PMID- 28983724 TI - Liver Function Assessment Using Albumin-Bilirubin Grade for Patients with Very Early-Stage Hepatocellular Carcinoma Treated with Radiofrequency Ablation. AB - BACKGROUND/AIM: Assessment of liver function is essential for management of hepatocellular carcinoma (HCC). Recently, albumin-bilirubin (ALBI) grade has been reported as a useful tool for assessing hepatic reserve in patients with HCC. The objective of this study was to determine whether ALBI grade could be used to predict the overall survival of very early-stage HCC patients treated with radiofrequency ablation (RF ablation). METHODS: A cohort of 368 patients with very early-stage HCC treated with RF ablation was retrospectively analyzed. The overall survival and recurrence-free survival were calculated in groups classified by ALBI grade and Child-Pugh score. RESULTS: Overall survival of patients with ALBI grade 1 was better than that of patients with ALBI grade 2 (5 year survival rate 88.5 vs. 73.8%, P < 0.001). In multivariable-adjusted model, ALBI grade was found to be an independent factor associated with overall survival (hazard ratio 2.44; 95% confidence interval 1.43-4.15). ALBI grade was able to stratify patients with distinct overall survival among patients within the same Child-Pugh score (5-year survival rate for Child-Pugh score 5: 88.5 vs. 76.6%, P = 0.002; for Child-Pugh score 6: 88.9 vs. 70.1%, P = 0.064). In contrast, Child Pugh score was unable to stratify patients with distinct overall survival within the same ALBI grade. CONCLUSIONS: Among patients with very early-stage HCC treated with RF ablation, ALBI grade was a good stratifying biomarker. ALBI grade was better tool for assessing liver function than Child-Pugh score for very early stage HCC treated with RF ablation. PMID- 28983725 TI - Liver transplantation for biliary atresia: a systematic review. AB - Biliary atresia (BA) is an idiopathic neonatal cholangiopathy characterized by progressive inflammatory obliteration of the intrahepatic or extrahepatic bile ducts. Although the Kasai operation has dramatically improved the outcomes in children with BA, most patients with BA eventually require liver transplantation (LT) even after undergoing a successful Kasai procedure. The Japanese LT Society (JLTS) was established in 1980 to characterize and follow trends in patient characteristics and the graft survival among all liver transplant patients in Japan. The 1-, 5-, 10-, 15- and 20-year survival rates for the patients and grafts undergoing living donor LT were 91.6, 91.5, 87.1, 85.4 and 84.2 and 90.5, 90.4, 84.6, 82.0 and 79.9%, respectively. LDLT was able to be performed even in patients weighing less than 5 kg with early liver failure following a Kasai operation using a reduced left lateral segments. As LT has been revealed to increase the donor pool and decrease the waiting list mortality with an excellent long-term graft survival, early referral to a transplant center should be considered when at least one complication of cirrhosis occurs during its natural history, especially in adolescents. PMID- 28983726 TI - Flexibility of individual multitasking strategies in task-switching with preview: are preferences for serial versus overlapping task processing dependent on between-task conflict? AB - The prevalence and the efficiency of serial and parallel processing under multiple task demands are highly debated. In the present study, we investigated whether individual preferences for serial or overlapping (parallel) processing represent a permanent predisposition or depend on the risk of crosstalk between tasks. Two groups (n = 91) of participants were tested. One group performed a classical task switching paradigm, enforcing a strict serial processing of tasks. The second group of participants performed the same tasks in a task-switching with-preview paradigm, recently introduced by Reissland and Manzey (2016), which in principle allows for overlapping processing of both tasks in order to compensate for switch costs. In one condition, the tasks included univalent task stimuli, whereas in the other bivalent stimuli were used, increasing risk of crosstalk and task confusion in case of overlapping processing. The general distinction of voluntarily occurring preferences for serial or overlapping processing when performing task switching with preview could be confirmed. Tracking possible processing mode adjustments between low- and high-crosstalk conditions showed that individuals identified as serial processors in the low crosstalk condition persisted in their processing mode. In contrast, overlapping processors split up in a majority adjusting to a serial processing mode and a minority persisting in overlapping processing, when working with bivalent stimuli. Thus, the voluntarily occurring preferences for serial or overlapping processing seem to depend at least partially on the risk of crosstalk between tasks. Strikingly, in both crosstalk conditions the individual performance efficiency was the higher, the more they processed in parallel. PMID- 28983727 TI - Binding pose and affinity prediction in the 2016 D3R Grand Challenge 2 using the Wilma-SIE method. AB - The Farnesoid X receptor (FXR) exhibits significant backbone movement in response to the binding of various ligands and can be a challenge for pose prediction algorithms. As part of the D3R Grand Challenge 2, we tested Wilma-SIE, a rigid protein docking method, on a set of 36 FXR ligands for which the crystal structures had originally been blinded. These ligands covered several classes of compounds. To overcome the rigid protein limitations of the method, we used an ensemble of publicly available structures for FXR from the PDB. The use of the ensemble allowed Wilma-SIE to predict poses with average and median RMSDs of 2.3 and 1.4 A, respectively. It was quite clear, however, that had we used a single structure for the receptor the success rate would have been much lower. The most successful predictions were obtained on chemical classes for which one or more crystal structures of the receptor bound to a molecule of the same class was available. In the absence of a crystal structure for the class, observing a consensus binding mode for the ligands of the class using one or more receptor structures of other classes seemed to be indicative of a reasonable pose prediction. Affinity prediction proved to be more challenging with generally poor correlation with experimental IC50s (Kendall tau ~ 0.3). Even when the 36 crystal structures were used the accuracy of the predicted affinities was not appreciably improved. A possible cause of difficulty is the internal energy strain arising from conformational differences in the receptor across complexes, which may need to be properly estimated and incorporated into the SIE scoring function. PMID- 28983728 TI - 17beta-estradiol and progesterone effect on human papillomavirus 16 positive cells grown as spheroid co-cultures. AB - Human papillomavirus (HPV) is the key epidemiologic factor of cervical cancer, but additional cofactors are mandatory. Estrogen has been considered as one of those. Here, the aim was to study the effects of steroid hormones on HPV16 E6-E7, estradiol receptors ERalpha and ERbeta, and progesterone receptor (PR) in HPV16 positive cervical carcinoma cell lines SiHa and CaSki grown as epithelial and fibroblast spheroid co-cultures. The spheroid co-cultures were exposured to 17beta-estradiol or progesterone from day 7 onwards. mRNA levels of HPV16 E6-E7, ERalpha, ERbeta and PR normalized against GAPDH were analyzed with quantitative reverse transcription-qPCR (RT-qPCR). 17beta-estradiol and progesterone decreased HPV16 E6-E7 mRNA expression in CaSki and increased in SiHA co-cultures. In CaSki co-cultures, ERbeta expression was blocked after 17beta-estradiol exposure while in SiHa cells it slightly increased ERbeta expression. PR expression was seen only in CaSki spheroids and it vanished after exposure to steroid hormones. Fibroblasts expressed all three hormone receptors as monolayers but ERbeta expression decreased and ERalpha and PR vanished after co-culturing. Cell culturing platform changes both oncogene and hormone receptor expression in HPV16 positive cervical cancer cell lines. This needs to be considered when in vitro results are extrapolated to in vivo situations. PMID- 28983729 TI - Increased CaSR and TRPC6 pulmonary vascular expression in the nitrofen-induced model of congenital diaphragmatic hernia. AB - AIMS AND OBJECTIVES: The high morbidity and mortality rates in congenital diaphragmatic hernia (CDH) are attributed primarily to severe lung hypoplasia and/or persistent pulmonary hypertension (PPH). PPH in CDH is characterized by abnormal vascular remodeling with thickening of medial and adventitial layers and extension of smooth muscle into previously nonmuscularized arteries. Excessive proliferation of pulmonary arterial smooth muscle cells (PASMC) is an important contributor to the concentric pulmonary arterial remodeling. An increase in cytosolic-free Ca2+ concentration in PASMC is a major trigger for pulmonary vasoconstriction and a key stimulus for PASMC proliferation and migration. Calcium-sensing receptor (CaSR), a member of the G-protein coupled receptor family, is activated by cations (e.g., Ca2+, Mg2+) and polyamines. Under normal physiological conditions, the expression levels of CaSR in the pulmonary vasculature are very low. Canonical transient receptor potential channels (TRPCs) constitute a series of nonselective cation channels with variable degree of Ca2+ selectivity. TRPC6 has been reported to play a crucial role in the regulation of neo-muscularization, vasoreactivity, and vasomotor tone in the pulmonary vasculature. We hypothesized that CaSR and TRPC6 expression is upregulated in the pulmonary vasculature of nitrofen-induced CDH rats. MATERIALS AND METHODS: Following ethical approval (REC1103), time-pregnant Sprague Dawley rats received nitrofen or vehicle on gestational day (D) 9. D21 fetuses were divided into CDH and control (n = 12). Quantitative real-time polymerase chain reaction (QRT-PCR), western blotting, and confocal-immunofluorescence microscopy were performed to detect lung gene and protein expression of CaSR and TRPC6. RESULTS: QRT-PCR and western blot analysis revealed that CaSR and TPRC6 expression was significantly increased in the CDH group compared to controls (p < 0.05). Confocal immunofluorescence microscopy revealed that CaSR and TRPC6 lung expression was markedly increased in CDH group compared to controls. CONCLUSION: Increased CaSR and TRPC6 expression in CDH lung suggests that CaSR interacting with TRPC6 may contribute to abnormal vascular remodeling resulting in pulmonary vasoconstriction and development of PPH. PMID- 28983730 TI - Associations between attention-deficit/hyperactivity disorder and autoimmune diseases are modified by sex: a population-based cross-sectional study. AB - Several studies have demonstrated associations between neuropsychiatric disorders, such as attention-deficit/hyperactivity disorder (ADHD), and the immune system, including autoimmune diseases. Since ADHD and many autoimmune diseases show sex-specific properties, such associations may also differ by sex. Using Norwegian national registries, we performed a cross-sectional study based on a cohort of 2,500,118 individuals to investigate whether ADHD is associated with common autoimmune diseases. Associations between ADHD and autoimmune diseases in females and males were investigated with logistic regression and effect modification by sex was evaluated. Several subanalyses were performed. The strongest association was found between ADHD and psoriasis in females, adjusted odds ratio (adjOR) = 1.57 (95% confidence interval: 1.46-1.68) and males, adjOR = 1.31 (1.23-1.40); p value for interaction < 0.0001. Furthermore, among females, ADHD was associated with Crohn's disease, adjOR = 1.44 (1.16-1.79) and ulcerative colitis, adjOR = 1.28 (1.06-1.54). In contrast, males with ADHD had lower odds of Crohn's disease, adjOR = 0.71 (0.54-0.92), in addition to a trend for lower odds of ulcerative colitis, adjOR = 0.86 (0.71-1.03); p values for interaction < 0.0001 and 0.0023, respectively. In a group of females where information on smoking and body mass index was available, adjustment for these potential mediators did not substantially alter the associations. Our findings support previously reported associations between ADHD and diseases of the immune system. The associations differ by sex, suggesting that sex-specific immune-mediated neurodevelopmental processes may be involved in the etiology of ADHD. PMID- 28983731 TI - Viral metagenomics of six bat species in close contact with humans in southern China. AB - Accumulating studies have shown that bats could harbor various important pathogenic viruses that could be transmitted to humans and other animals. Extensive metagenomic studies of different organs/tissues from bats have revealed a large number of novel or divergent viruses. To elucidate viral diversity and epidemiological and phylogenetic characteristics, six pooled fecal samples from bats were generated (based on bat species and geographic regions characteristic for virome analysis). These contained 500 fecal samples from six bat species, collected in four geographic regions. Metagenomic analysis revealed a plethora of divergent viruses originally found in bats. Multiple contigs from influenza A virus and coronaviruses in bats shared high identity with those from humans, suggesting possible cross-species transmission, whereas a number of contigs, whose sequences were taxonomically classifiable within Alphapapillomavirus, Betaretrovirus, Alpharetrovirus, Varicellovirus, Cyprinivirus, Chlorovirus and Cucumovirus had low identity to viruses in existing databases, which indicated possible evolution of novel viral species. None of the established caliciviruses and picornaviruses were found in the 500 fecal specimens. Papillomaviruses with high amino acid identity were found in Scotophilus kuhlii and Rhinolophus blythi, challenging the hypotheses regarding the strict host specificity and co-evolution of papillomaviruses. Phylogenetic analysis showed that four bat rotavirus A strains might be tentative G3 strains, according to the Rotavirus Classification Working Group classification. PMID- 28983732 TI - Publishing in black and white: the relevance of listing of scientific journals. AB - Scientific publishing, including in the field of Rheumatology, is evolving rapidly. Predatory journals are one of the major threats to contemporary publishing, especially to eager and naive authors. In this narrative review, we discuss mechanisms that authors can employ to white list genuine scientific journals and blacklist "predatory" ones. Inclusion of a journal in reputed indices such as Medline (but not just Pubmed), Web of Science, Scopus or Embase raises the likelihood that the journal is genuine, more so if it is included in the current Journal Citation Reports. Other commercially available whitelists also exist, so also whitelists published by regulatory authorities in some countries. A commercially available blacklist has emerged since the very useful Beall's blacklist became defunct. In the absence of access to a whitelist or blacklist, certain characteristics such as repeated email solicitations for articles with an extremely narrow deadline from unknown sources, lack of inclusion in reputed indices, journals not published or endorsed by national or international society and scarcity of currently published articles should render authors suspicious of the genuine nature of a journal. National societies should work together to generate subject-specific (including Rheumatology specific) whitelists that can be available free of cost to authors from all over the world. PMID- 28983733 TI - Bacterial and fungal biodeterioration of discolored building paints in Lagos, Nigeria. AB - Microbial induced discolorations are an unsightly feature occurring on painted walls in Lagos, the commercial hub of Nigeria. Very few studies have been carried out conventionally about the microbial community structure of discolored painted walls in Nigeria therefore, knowledge of the true microbial diversity is elusive. To further our understanding of the phylogenetic diversity of representative microbial community on 40 discolored and three clean-looking buildings, a comparative DNA sequence analysis of 16S rDNA genes was undertaken. Following DNA extraction, portions of the rDNA genes were amplified by PCR and sequenced. Resulting sequences were compared with GenBank data base sequences. Fifteen unique fungal sequences and one bacterial sequence were obtained. Majority (37.50%) of rDNA sequences analyzed, represent the genus Meyerozyma of which the novel fungus Meyerozyma guilliermondii, which to our knowledge, has not yet been implicated in painted walls was detected. Clones from the discolored painted wall isolates also produced a data set in which 31.25% of sequences were related to Fusarium proliferatum and 6.25% were Pseudomonas aeruginosa. The remaining sequences clustered with members of the genera Candida (6.25%), Aspergillus (12.5%) and Cerrena (6.25%). The study provides reliable data on microbial communities on painted walls and information for paint biocide formulation. PMID- 28983734 TI - Anti-inflammatory Effects of Enhanced Recovery Programs on Early-Stage Colorectal Cancer Surgery. AB - BACKGROUND: Postoperative ileus (POI) is observed in 20-30% of patients undergoing colorectal cancer surgery, despite enhanced recovery programs (ERPs). Cyclooxygenase (COX)-2 is identified as a key enzyme in POI, but other arachidonic acid pathway enzymes have received little attention despite their potential as selective targets to prevent POI. The objectives were to compare the expression of arachidonic acid metabolism (AAM) enzymes (1) between patients who underwent colorectal cancer surgery and followed an ERP or not (NERP), (2) and between ERP patients who experimented POI or not and (3) to determine the ability of antagonists of these pathways to modulate contractile activity of colonic muscle. METHODS: This was a translational study. Main outcome measures were gastrointestinal motility recovery data, mRNA expressions of key enzymes involved in AAM (RT-qPCR) and ex vivo motility values of the circular colon muscle. Twenty eight prospectively included ERP patients were compared to eleven retrospectively included NERP patients that underwent colorectal cancer surgery. RESULTS: ERP reduced colonic mucosal COX-2, microsomal prostaglandin E synthase (mPGES1) and hematopoietic prostaglandin D synthase (HPGDS) mRNA expression. mPGES1 and HPGDS mRNA expression were significantly associated with ERP compliance (respectively, r2 = 0.25, p = 0.002 and r2 = 0.6, p < 0.001). In muscularis propria, HPGDS mRNA expression was correlated with GI motility recovery (p = 0.002). The pharmacological inhibition of mPGES1 increased spontaneous ex vivo contractile activity in circular muscle (p = 0.03). CONCLUSION: The effects of ERP on GI recovery are correlated with the compliance of ERP and could be mediated at least in part by mPGES1, HPGDS and COX-2. Furthermore, mPGES1 shows promise as a therapeutic target to further reduce POI duration among ERP patients. PMID- 28983735 TI - Cancer-related loneliness mediates the relationships between social constraints and symptoms among cancer patients. AB - Cancer patients have high rates of persistent and disabling symptoms. Evidence suggests that social constraints (e.g., avoidance and criticism) negatively impact symptoms, but pathways linking these variables have yet to be identified. This study examined whether cancer-related loneliness (i.e., feeling socially disconnected related to having cancer) mediated the relationships between social constraints and symptoms (i.e., pain interference, fatigue, sleep disturbance, and cognitive complaints) in patients with various cancers (N = 182). Patients (51% female, mean age = 59) were recruited from the Indiana Cancer Registry and completed questionnaires assessing social constraints, cancer-related loneliness, and symptoms. Structural equation modeling was used to evaluate the hypothesized relationships among variables. The model demonstrated good fit. Consistent with our hypothesis, cancer-related loneliness mediated the relationships between social constraints and each symptom. Findings suggest that addressing cancer related loneliness in symptom management interventions may mitigate the negative impact of social constraints on outcomes. PMID- 28983736 TI - The Swedish cause of death register. AB - Sweden has a long tradition of recording cause of death data. The Swedish cause of death register is a high quality virtually complete register of all deaths in Sweden since 1952. Although originally created for official statistics, it is a highly important data source for medical research since it can be linked to many other national registers, which contain data on social and health factors in the Swedish population. For the appropriate use of this register, it is fundamental to understand its origins and composition. In this paper we describe the origins and composition of the Swedish cause of death register, set out the key strengths and weaknesses of the register, and present the main causes of death across age groups and over time in Sweden. This paper provides a guide and reference to individuals and organisations interested in data from the Swedish cause of death register. PMID- 28983737 TI - The chromosome 6q22.33 region is associated with age at diagnosis of type 1 diabetes and disease risk in those diagnosed under 5 years of age. AB - AIMS/HYPOTHESIS: The genetic risk of type 1 diabetes has been extensively studied. However, the genetic determinants of age at diagnosis (AAD) of type 1 diabetes remain relatively unexplained. Identification of AAD genes and pathways could provide insight into the earliest events in the disease process. METHODS: Using ImmunoChip data from 15,696 cases, we aimed to identify regions in the genome associated with AAD. RESULTS: Two regions were convincingly associated with AAD (p < 5 * 10-8): the MHC on 6p21, and 6q22.33. Fine-mapping of 6q22.33 identified two AAD-associated haplotypes in the region nearest to the genes encoding protein tyrosine phosphatase receptor kappa (PTPRK) and thymocyte expressed molecule involved in selection (THEMIS). We examined the susceptibility to type 1 diabetes at these SNPs by performing a meta-analysis including 19,510 control participants. Although these SNPs were not associated with type 1 diabetes overall (p > 0.001), the SNP most associated with AAD, rs72975913, was associated with susceptibility to type 1 diabetes in those individuals diagnosed at less than 5 years old (p = 2.3 * 10-9). CONCLUSION/INTERPRETATION: PTPRK and its neighbour THEMIS are required for early development of the thymus, which we can assume influences the initiation of autoimmunity. Non-HLA genes may only be detectable as risk factors for the disease in individuals diagnosed under the age 5 years because, after that period of immune development, their role in disease susceptibility has become redundant. PMID- 28983739 TI - Removal of NO with the hexamminecobalt solution catalyzed by the carbon treated with oxalic acid. AB - NO can be removed at the same time with SO2 by aqueous Co(NH3)62+ solution. The reduction of Co(NH3)63+ to Co(NH3)62+ is catalyzed by activated carbon to regain the NO absorption ability of the scrubbing solution. Oxalic acid solution is explored to change the carbon surface to ameliorate its catalytic capability. The experimental results suggest that the best catalyst is prepared by impregnating the carbon sample in 0.7 mol l-1 oxalic acid solution for 24 h followed by being activated at 600 degrees C for 5 h under nitrogen atmosphere. After being treated with oxalic acid solution, the surface area and the acidity on the carbon surface increase. The experiments show that the carbon modified with oxalic acid can get a much higher NO removal efficiency than the original carbon. PMID- 28983738 TI - Establishing clinical severity for PROMIS(r) measures in adult patients with rheumatic diseases. AB - PURPOSE: Different patient-reported outcome (PRO) measures are used for rheumatic diseases (RD). The aims of this study are-(1) Identify PROMIS(r) domains most relevant to care of patients with RD, (2) Collect T-Score metrics in patients with RD, and (3) Identify clinically meaningful cut-points for these domains. METHODS: A convenience sample of RD patients was recruited consecutively during clinic visits, and asked to complete computer-adaptive tests on thirteen Patient Reported Outcomes Measurement Information System (PROMIS(r)) instruments. Based on discussion with clinical providers, four measures were chosen to be relevant and actionable (from rheumatologists' perspective) in RD patients. Data from RD patients were used to develop clinical vignettes across a range of symptom severity. Vignettes were created based on most likely item responses at different levels on the T-score metric (mean = 50; SD = 10) and anchored at 5-point intervals (0.5 SDs). Patients with RD (N = 9) and clinical providers (N = 10) participated as expert panelists in separate one-day meetings using a modified educational standard setting method. RESULTS: Four domains (physical function, pain interferences, sleep disturbance, depression) that are actionable at the point-of-care were selected. For all domains, patients endorsed cut-points at lower levels of impairment than providers by 0.5 to 1 SD (e.g., severe impairment in physical function was defined as a T-score of 35 by patients and 25 by providers). CONCLUSIONS: We used a modified educational method to estimate clinically relevant cut-points to classify severity for PROMIS measures This allows for meaningful interpretation of PROMIS(r) measures in a clinical setting of RD population. PMID- 28983740 TI - Experimental Toxoplasma gondii and Eimeria tenella co-infection in chickens. AB - The widespread apicomplexan parasites Toxoplasma gondii (T. gondii) and Eimeria tenella (E. tenella) are important pathogens with high prevalence in poultry. The aim of our study was the investigation of mutual influences in co-infected chickens, focusing on immune response and course of infection. Two separate trials were performed using in total 96 1-day-old chickens, divided into four study groups: group NC (negative control, uninfected), group PC-T (oral or intramuscular infection with T. gondii oocysts (trial 1) or tachyzoites (trial 2), respectively), group PC-E (oral infection with E. tenella (trial 1) or E. tenella and Eimeria acervulina (trial 2)), and group TE (co-infection). T. gondii and Eimeria infections were validated by different parameters, and cytokine expression in the gut and spleen was investigated. T. gondii-specific antibodies were detected earliest 4 days post infection (p.i.) by immunoblot and direct DNA detection was possible in 22.1% of all tissue samples from infected chickens. Eimeria spp. merogony seemed to be enhanced by co-infection with T. gondii, interestingly without marked differences in oocyst excretion between co-infected and Eimeria spp. mono-infected chickens. An increase of messenger RNA (mRNA) expression of Th1- (IFN-gamma, IL-12, TNF-alpha) and Th2-related cytokines (IL 10) mainly in groups PC-E and TE was observed, however, without statistically significant differences between co-infection and single infection with Eimeria. In conclusion, most of the measurable immune response could be attributed to Eimeria infection. To the best of our knowledge, this is the first report on co infection experiments of T. gondii with Eimeria spp. in chickens. PMID- 28983741 TI - What Do High-Risk Patients Value? Perspectives on a Care Management Program. AB - BACKGROUND: There is growing interest in coordinating care for high-risk patients through care management programs despite inconsistent results on cost reduction. Early evidence suggests patient-centered benefits, but we know little about how participants engage with the programs and what aspects they value. OBJECTIVE: To explore care management program participants' awareness and perceived utility of program offerings. DESIGN: Cross-sectional telephone survey administered December 2015-January 2016. PARTICIPANTS: Patients enrolled in a Boston-area primary care based care management program. MAIN MEASURES: Our main outcome was the number of topics in which patients reported having "very helpful" interactions with their care team in the past year. We analyzed awareness of one's care manager as an intermediate outcome, and then as a primary predictor of the main outcome, along with patient demographics, years in the program, attitudes, and worries as secondary predictors. KEY RESULTS: The survey response rate was 45.8% (n = 1220); non-respondents were similar to respondents. More respondents reported worrying about family (72.8%) or financial issues (52.5%) than about their own health (41.6%). Seventy-four percent reported care manager awareness, particularly women (OR 1.33, 95% CI 1.01-1.77) and those with more years in the program (OR 1.16, 95% CI 1.03-1.30). While interaction rates ranged from 19.8% to 72.4% across topics, 81.3% rated at least one interaction as very helpful. Those who were aware of their care manager reported very helpful interactions on more topics (OR 2.77, 95% CI 2.15-3.56), as did women (OR 1.25, 95% CI 1.00-1.55), younger respondents (OR 0.98 for older age, 95% CI 0.97-0.99), and those with higher risk scores (OR 1.04, 95% CI 1.02-1.06), preference for deferring treatment decisions to doctors (OR 2.00, 95% CI 1.60-2.50), and reported control over their health (OR 1.67, 95% CI 1.33-2.10). CONCLUSIONS: High-risk patients reported helpful interactions with their care team around medical and social determinants of health, particularly those who knew their care manager. Promoting care manager awareness may help participants make better use of the program. PMID- 28983742 TI - Multi-resolution geometric modeling of the mitral heart valve leaflets. AB - An essential element of cardiac function, the mitral valve (MV) ensures proper directional blood flow between the left heart chambers. Over the past two decades, computational simulations have made marked advancements toward providing powerful predictive tools to better understand valvular function and improve treatments for MV disease. However, challenges remain in the development of robust means for the quantification and representation of MV leaflet geometry. In this study, we present a novel modeling pipeline to quantitatively characterize and represent MV leaflet surface geometry. Our methodology utilized a two-part additive decomposition of the MV geometric features to decouple the macro-level general leaflet shape descriptors from the leaflet fine-scale features. First, the general shapes of five ovine MV leaflets were modeled using superquadric surfaces. Second, the finer-scale geometric details were captured, quantified, and reconstructed via a 2D Fourier analysis with an additional sparsity constraint. This spectral approach allowed us to easily control the level of geometric details in the reconstructed geometry. The results revealed that our methodology provided a robust and accurate approach to develop MV-specific models with an adjustable level of spatial resolution and geometric detail. Such fully customizable models provide the necessary means to perform computational simulations of the MV at a range of geometric accuracies in order to identify the level of complexity required to achieve predictive MV simulations. PMID- 28983743 TI - PET Imaging of Human Brown Adipose Tissue with the TSPO Tracer [11C]PBR28. AB - PURPOSE: Brown adipose tissue (BAT) in adult humans has been recently rediscovered and intensively investigated as a new potential therapeutic target for obesity and type 2 diabetes (T2D). However, reliable assessment of BAT mass in vivo represents a considerable challenge. The purpose of this investigation is to demonstrate for the first time that human BAT depots can be imaged with a translocator protein (TSPO)-specific positron emission tomography (PET) tracer [11C]PBR28 under thermoneutral conditions. PROCEDURES: In this retrospective analysis, we analyzed the images of three healthy volunteers who underwent PET/magnetic resonance (MR) imaging after injection of 14 m Ci of [11C]PBR28 at room temperature. Thirty-minute static PET images were reconstructed from the data obtained 60-90 min after the injection of the tracer. RESULTS: [11C]PBR28 uptake in the neck/supraclavicular regions was identified, which was parallel to the known distribution pattern of human BAT depots. These areas co-localized with the areas of hyperintensity and corresponded to fat on T1-weighted MR images. Standardized uptake value (SUV) was used to quantify [11C]PBR28 signal in BAT depots. The average (+/- SD) SUV(mean) and SUVmax for BAT depots was 2.13 (+/- 0.33) and 3.19 (+/- 0.34), respectively, while the average SUV(mean) for muscle and subcutaneous adipose tissue was 0.79 (+/- 0.1) and 0.18 (+/- 0.04), respectively. CONCLUSIONS: In this brief article, we provide the first evidence suggesting that [11C]PBR28, a widely available TSPO-specific PET tracer, can be used for imaging human BAT mass under thermoneutral conditions. PMID- 28983744 TI - Human papillomavirus genotype distribution among HPV-positive women in Sichuan province, Southwest China. AB - In this hospital-based descriptive study, the genotype distribution of human papillomavirus (HPV) among HPV-infected women were investigated in 4,305 gynecological patients in Sichuan province. Females attending gynecology clinics between March 2014 and March 2015 were subjected to HPV screening after giving informed consent. Cervical scrapings were examined by cytopathology and colposcopy-directed biopsies. HPV genotyping was performed on a Luminex 200 system. Seventeen high-risk (HR) genotypes (HPV-16, -18, -31, -33, -35, -39, -45, -51, -52, -53, -56, -58, -59, -66, -68, -73, and -82) and seven low-risk (LR) genotypes (HPV-6, -11, -42, -43, -61, -81, and -83) were detected. Among all HPV positive women, 34.1% (1,467/4,305) of the cases showed abnormal cytology and biopsy, including high-grade squamous lesions (HSIL), cervical intraepithelial neoplasias of grades 2 and 3 (CIN2/CIN3), and cervical cancer (CC). HPV-16, -52, and -58 were the predominant genotypes, followed by HPV-56, -18, -59, -39, -53, 33, and -81. A total of 3,785 (87.9%) HPV positive women were found to have HR HPV infection, while 859 (20.0%) were found to have LR HPV infection. Among all patients, 79% (3,401/4,305) were infected with a single strain of HPV, 85.5% (2,907/3,401) cases of which were of the HR HPV genotype. In cervical precancerous lesions (CPLs) and CC patients, HR HPV-16, -58, -52, -33, and -18 were the predominant genotypes. Interestingly, 33 CPL patients had a single LR HPV infection with HPV-61, -11, -81, -6, -43, or -42. Furthermore, one CC patient was infected only with LR HPV-11. According to the abundant genotype diversity of HPV in Sichuan, we suggest that a large-scale epidemiological investigation should be launched, not only to understand the distribution of HPV genotype, but also to provide information needed for HPV vaccination programs and to predict the effectiveness of current vaccines in Southwest China. PMID- 28983745 TI - Physical and Chemical Enhancement of and Adaptive Resistance to Irreversible Electroporation of Pancreatic Cancer. AB - Irreversible electroporation (IRE) can be used to treat cancer by electrical pulses, with advantages over traditional thermal approaches. Here we assess for the first time the IRE response of pancreatic cancer, one of the deadliest forms of cancer, both in vitro and in vivo. We demonstrate that both established and primary cancer cell lines can be destroyed by IRE, but with differential susceptibility and thresholds. We further demonstrate in vitro that viability for a given IRE dose can vary with the local chemistry as outcomes were shown to depend on suspending medium and reduction of glucose in the media significantly improved IRE destruction. Data here also demonstrate that repeated IRE treatments can lead to adaptive resistance in pancreatic carcinoma cells thereby reducing subsequent treatment efficacy. In addition, we demonstrate that physical enhancement of IRE, by re-arranging the pulse sequences without increasing the electrical energy delivered, achieve reduced viability in vitro and decreased tumor growth in an in vivo xenograft model. Together, these results show that IRE can destroy pancreatic cancer in vitro and in vivo, that there are both chemical and physical enhancements that can improve tumor destruction, and that one should guard against adaptive resistance when performing repeated treatments. PMID- 28983746 TI - Performance of Granular Starch with Controlled Pore Size during Hydrolysis with Digestive Enzymes. AB - Studies on porous starch have been directed to explore different industrial applications as bio-adsorbents of a variety of compounds. However, the analysis of starch digestibility is essential for food application. The objective of this study was to determine the impact of porous structure on in vitro starch digestibility. Porous starches were obtained using a range of concentrations of amyloglucosidase (AMG), alpha-amylase (AM), cyclodextrin-glycosyltransferase (CGTase) or branching enzyme (BE). Porous starches exhibited major content of digestible starch (DS) that increased with the intensity of the enzymatic treatment, and very low amount of resistant starch (RS). Porous starches behaved differently during in vitro hydrolysis depending on their enzymatic treatment. AMG was the unique treatment that increased the digestive amylolysis and estimated glycemic index, whereas AM, CGTase and BE reduced them. A significant relationship was found between the pore size and the severity of the amylolysis, suggesting that a specific pore size is required for the accessibility of the digestive amylase. Therefore, pore size in the starch surface was a limiting factor for digestion of starch granules. PMID- 28983747 TI - Relative importance of climate changes at different time scales on net primary productivity-a case study of the Karst area of northwest Guangxi, China. AB - Climate changes are considered to significantly impact net primary productivity (NPP). However, there are few studies on how climate changes at multiple time scales impact NPP. With MODIS NPP product and station-based observations of sunshine duration, annual average temperature and annual precipitation, impacts of climate changes at different time scales on annual NPP, have been studied with EEMD (ensemble empirical mode decomposition) method in the Karst area of northwest Guangxi, China, during 2000-2013. Moreover, with partial least squares regression (PLSR) model, the relative importance of climatic variables for annual NPP has been explored. The results show that (1) only at quasi 3-year time scale do sunshine duration and temperature have significantly positive relations with NPP. (2) Annual precipitation has no significant relation to NPP by direct comparison, but significantly positive relation at 5-year time scale, which is because 5-year time scale is not the dominant scale of precipitation; (3) the changes of NPP may be dominated by inter-annual variabilities. (4) Multiple time scales analysis will greatly improve the performance of PLSR model for estimating NPP. The variable importance in projection (VIP) scores of sunshine duration and temperature at quasi 3-year time scale, and precipitation at quasi 5-year time scale are greater than 0.8, indicating important for NPP during 2000-2013. However, sunshine duration and temperature at quasi 3-year time scale are much more important. Our results underscore the importance of multiple time scales analysis for revealing the relations of NPP to changing climate. PMID- 28983748 TI - Changes in Adult BMI and Waist Circumference Are Associated with Increased Risk of Advanced Colorectal Neoplasia. AB - BACKGROUND: Waist circumference (WC) is a stronger predictor of colon cancer (CRC) risk than body mass index (BMI). However, how well change in either WC or BMI predicts risk of advanced colorectal neoplasia (AN) is unclear. AIMS: To determine the relationship between change in BMI and WC from early adulthood to later age and the risk of AN and which change measure is a stronger predictor. METHODS: In 4500 adults, ages 50-80, with no previous neoplasia and undergoing screening colonoscopy, BMI and WC at age 21 and at time of screening were reported. Changes in BMI and WC were defined using universal risk cutoffs. Known CRC risk factors were controlled in the logistic models. RESULTS: Overall, model statistics showed WC change (omnibus test chi 2 = 10.15, 2 DF, p value = 0.006) was a statistically stronger predictor of AN than BMI change (omnibus test chi 2 = 5.66, 5 DF, p value = 0.34). Independent of BMI change, participants who increased WC (OR 1.44; 95% CI 1.05-1.96) or maintained a high-risk WC (OR 2.50; 95% CI 1.38-4.53) at age 21 and at screening had an increased risk of AN compared to those with a low-risk WC. Study participants who were obese at age 21 and at screening had an increased risk of AN (OR 1.87; 95% CI 1.08-3.23) compared to those who maintained a healthy BMI. Maintaining an overweight BMI or increasing BMI was not associated with AN. CONCLUSIONS: Maintaining an unhealthy BMI and WC throughout adult life may increase risk of AN. WC change may be a better predictor of AN than BMI change. PMID- 28983749 TI - First study of hormesis effect on mushroom cultivation. AB - The use of fungicides is common in mushroom cultivation, but no study was carried out applying reduced doses of fungicides in order to increase yield, taking account the hormesis effect. The aim of this manuscript was to verify the effects of different concentrations of fungicides to stimulate the productivity of different strains of Agaricus bisporus. Two stages were developed, an in vitro study to define the best concentration to be applied in the second experiment an agronomic study, which consisted of the application of the selected fungicides, in their respective concentrations, in an experiment carried out in the mushroom chamber. Clearly, the result of the hormesis effect on mushroom cultivation can be verified. The results obtained in the 1st stage of the study (in vitro) were not always reproduced in the 2nd stage of the study (in vivo). The kresoxim methyl active ingredient may be an important chemical agent, while strain ABI 15/01 may be an extremely important biological agent to increase yield in the study of hormesis effects. PMID- 28983750 TI - Preliminary study on magnetic tracking-based planar shape sensing and navigation for flexible surgical robots in transoral surgery: methods and phantom experiments. AB - PURPOSE: Flexible surgical robot can work in confined and complex environments, which makes it a good option for minimally invasive surgery. In order to utilize flexible manipulators in complicated and constrained surgical environments, it is of great significance to monitor the position and shape of the curvilinear manipulator in real time during the procedures. In this paper, we propose a magnetic tracking-based planar shape sensing and navigation system for flexible surgical robots in the transoral surgery. The system can provide the real-time tip position and shape information of the robot during the operation. METHODS: We use wire-driven flexible robot to serve as the manipulator. It has three degrees of freedom. A permanent magnet is mounted at the distal end of the robot. Its magnetic field can be sensed with a magnetic sensor array. Therefore, position and orientation of the tip can be estimated utilizing a tracking method. A shape sensing algorithm is then carried out to estimate the real-time shape based on the tip pose. With the tip pose and shape display in the 3D reconstructed CT model, navigation can be achieved. RESULTS: Using the proposed system, we carried out planar navigation experiments on a skull phantom to touch three different target positions under the navigation of the skull display interface. During the experiments, the real-time shape has been well monitored and distance errors between the robot tip and the targets in the skull have been recorded. The mean navigation error is [Formula: see text] mm, while the maximum error is 3.2 mm. CONCLUSION: The proposed method provides the advantages that no sensors are needed to mount on the robot and no line-of-sight problem. Experimental results verified the feasibility of the proposed method. PMID- 28983751 TI - Surgical Management of Gastrogastric Fistula After Roux-en-Y Gastric Bypass: 10 Year Experience. AB - BACKGROUND: Gastrogastric fistula (GGF) occurs in 1-6% of patients who undergo Roux-en-Y gastric bypass (RYGB) for morbid obesity. The pathophysiology may be related to gastric ischemia, fistula, or ulcer. OBJECTIVES: The purposes of the study are to describe the principles of management and to review the literature of this uncommon complication. SETTING: The setting of this study is University Hospital, France. MATERIALS AND METHODS: We conducted a retrospective review of all patients' records with a diagnosis of GGF after RYGB between January 2004 and November 2014. RESULTS: During the study period, 1273 patients had RYGB for morbid obesity. Fifteen patients presented with a symptomatic GGF (1.18%). The average interval from surgery to presentation was 28 months (22-62). A history of marginal ulcer or anastomotic leak was present in nine patients (60%). The most common presentation was weight regain (80%), followed by pain (73.3%). Two types of fistulas were identified, an exclusively GGF (high) and a gastro-jejuno gastric fistula (low). High GGF, frequently associated with dilatation of the gastric pouch, was treated by a sleeve of the pouch and sleeve resection of the remnant stomach (nine patients). Low GGF was treated with gastric resection coupled with a revision of the gastrojejunal anastomosis (six patients). All patients were treated laparoscopically with no conversion to laparotomy. The average length of postoperative hospital stay was 5.2 days (range 3-10). CONCLUSION: GGF after RYGB is a rare complication. Its pathophysiology remains unclear. Surgical management is the definitive treatment. PMID- 28983752 TI - Cytotoxicity and apoptotic cell death induced by Vitis vinifera peel and seed extracts in A431 skin cancer cells. AB - Vitis vinifera. L is one of the most widely consumed fruits in the world and are rich in antioxidant abundant polyphenols. The present study was carried out to assess the antiproliferative and apoptotic effects of Vitis vinifera peel and seed extracts in an in vitro model using human epidermoid carcinoma A431 cell lines. Vitis vinifera peel and seed extracts were incubated with A431 cells to evaluate the antiproliferative, apoptotic effects and the morphological apoptotic changes induced by the extracts. Mitochondrial membrane potential was also measured after incubating the cells with extracts. At the inhibitory concentration (IC50), grape seed extract (111.11 ug/mL) and grape peel extract (319.14 ug/mL) were incubated for 24 h with A431 cells. Vitis vinifera peel and seed extracts were able to impart cytotoxic effects, induced apoptosis and apoptotic morphological changes in A431 cells significantly (p < 0.01) and this effect is associated with the interference with mitochondrial membrane potential. This reduction in mitochondrial membrane potential probably initiated the apoptotic cascade in the extracts treated cells. Vitis vinifera peel and seed phytochemicals can selectively target cancer cells and the phytochemicals that are occluded can serve as potential anticancer agents providing better efficacy in killing cancer cells. PMID- 28983754 TI - Regarding ligature induced blister formation in hanging - the "pinch" effect. PMID- 28983753 TI - Temporal Variation of White Rhino Dung Odours. AB - In order for an olfactory signal to be effective, it must persist in the environment for an extended period. White rhino dung odours transmit information about sex, age, territorial and oestrous states. As these odours relay important information, temporal changes in the odour emission rate and/or composition may be critical in order for other individuals to obtain this information. Here, we examine how the dung odours of adult white rhinos (male: territorial and non territorial; female: oestrous and non-oestrous) change over the short (hours) and long (seasons) term using headspace extraction. Additionally, we measure seasonal midden visitation and defecation frequency to link behaviours to seasonal changes in odour longevity. We found that during the dry season, territorial male dung odours persisted for 48 hours, while the odours of all other adults persisted for >48 hours. The high temperature and humidity of the wet season did not affect odour longevity of oestrous females, but decreased dung odour longevity (i.e. increased emission) of territorial males, non-territorial males, and non-oestrous females. Despite this reduction, neither males nor females adjusted their seasonal visitation or defecation frequency. With regard to a temporal indicator, 3,7-dimethly-1,6-octadiene signalled dung age during the wet season, while acetophenone signalled dung age during the dry season. Ultimately, our results provide the first detailed account of temporal changes of dung VOCs, and highlight the limitations of dung as a signalling medium. PMID- 28983756 TI - Effects of photobiomodulation therapy and topical non-steroidal anti-inflammatory drug on skeletal muscle injury induced by contusion in rats-part 1: morphological and functional aspects. AB - Musculoskeletal injuries are very frequent and are responsible for causing pain and impairment of muscle function, as well as significant functional limitations. In the acute phase, the most prescribed treatment is with non-steroidal anti inflammatory drugs (NSAIDs), despite their questionable effectiveness. However, the use of photobiomodulation therapy (PBMT) in musculoskeletal disorders has been increasing in the last few years, and this therapy appears to be an interesting alternative to the traditional drugs. The objective of the present study was to evaluate and compare the effects of PBMT, with different application doses, and topical NSAIDs, under morphological and functional parameters, during an acute inflammatory process triggered by a controlled model of musculoskeletal injury induced via contusion in rats. Muscle injury was induced by means of a single trauma to the animals' anterior tibialis muscle. After 1 h, the rats were treated with PBMT (830 nm; continuous mode, with a power output of 100 mW; 3.57 W/cm2; 1 J-35.7 J/cm2, 3 J-107.1 J/cm2, and 9 J-321.4 J/cm2; 10, 30, and 90 s) or diclofenac sodium for topical use (1 g). Morphological analysis (histology) and functional analysis (muscle work) were performed, 6, 12, and 24 h after induction of the injury. PBMT, with all doses tested, improved morphological changes caused by trauma; however, the 9 J (321.4 J/cm2) dose was the most effective in organizing muscle fibers and cell nuclei. On the other hand, the use of diclofenac sodium produced only a slight improvement in morphological changes. Moreover, we observed a statistically significant increase of muscle work in the PBMT 3 J (107.1 J/cm2) group in relation to the injury group and the diclofenac group (p < 0.05). The results of the present study indicate that PBMT, with a dose of 3 J (107.1 J/cm2), is more effective than the other doses of PBMT tested and NSAIDs for topical use as a means to improve morphological and functional alterations due to muscle injury from contusion. PMID- 28983757 TI - Evaluation of the accuracy of estimated baseline serum creatinine for acute kidney injury diagnosis. AB - BACKGROUND: Modern epidemiologic studies of acute kidney injury (AKI) have been facilitated by the increasing availability of electronic medical records. However, pre-morbid reference serum creatinine (SCr) data are often unavailable in such records. Investigators substitute estimated baseline SCr with the eGFR 75 approach, instead of using actually measured baseline SCr. Here, we evaluated the accuracy of estimated baseline SCr for AKI diagnosis in the Japanese population. METHODS: Inpatients and outpatients aged 18-80 years were retrospectively enrolled. AKI was diagnosed according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria, using SCr levels. The non-AKI and AKI groups were selected using the following criteria: increase 1.5 times greater than baseline SCr ("baseline SCr") or increase 0.3 mg/dL greater than baseline SCr in 48 h ("increase in 48 h"). AKI accuracy defined by the estimated reference SCr, the average SCr value of the non-AKI population (eb-GFR-A approach), or the back calculated SCr from fixed eGFR = 75 mL/min/1.73 m2 (eGFR 75 approach, or, eb-GFR B approach in this study), was evaluated. RESULTS: We analyzed data from 131,358 Japanese patients. The number of patients with reference baseline SCr in the non AKI and AKI patients were 29,834 and 8952, respectively. For AKI patients diagnosed using "baseline SCr", the AKI diagnostic accuracy rates as defined by eb-GFR-A and eb-GFR-B were 63.5 and 57.7%, respectively, while in AKI diagnosed using "increase in 48 h", the AKI diagnostic accuracy rates as defined by eb-GFR A and eb-GFR-B were 78.7 and 75.1%, respectively. In non-AKI patients, false positive rates of AKI misdiagnosed via eb-GFR-A and eb-GFR-B were 7.4 and 6.8%, respectively. CONCLUSIONS: AKI diagnosis using the average SCr value of the general population may yield more accurate results than diagnosis using the eGFR 75 approach when the reference SCr is unavailable. PMID- 28983758 TI - Biotechnological production of bio-based long-chain dicarboxylic acids with oleogenious yeasts. AB - Long-chain alpha,omega-dicarboxylic acids (DCAs) are versatile chemical intermediates of industrial importance used as building blocks for the production of polymers, lubricants, or adhesives. The majority of industrial long-chain DCAs is produced from petro-chemical resources. An alternative is their biotechnological production from renewable materials like plant oil fatty acids by microbial fermentation using oleogenious yeasts. Oleogenious yeasts are natural long-chain DCA producers, which have to be genetically engineered for high-yield DCA production. Although, some commercialized fermentation processes using engineered yeasts are reported, bio-based long-chain DCAs are still far from being a mass product. Further progress in bioprocess engineering and rational strain design is necessary to advance their further commercialization. The present article reviews the basic strategies, as well as novel approaches in the strain design of oleogenious yeasts, such as the combination of traditional metabolic engineering with system biology strategies for high-yield long-chain DCA production. Therefore a detailed overview of the involved metabolic processes for the biochemical long-chain DCA synthesis is given. PMID- 28983759 TI - Myocardial dysfunction after out-of-hospital cardiac arrest: predictors and prognostic implications. AB - We aim to determine the incidence of early myocardial dysfunction after out-of hospital cardiac arrest, risk factors associated with its development, and association with outcome. A retrospective chart review was performed among consecutive out-of-hospital cardiac arrest (OHCA) patients who underwent echocardiography within 24 h of return of spontaneous circulation at three urban teaching hospitals. Our primary outcome is early myocardial dysfunction, defined as a left ventricular ejection fraction < 40% on initial echocardiogram. We also determine risk factors associated with myocardial dysfunction using multivariate analysis, and examine its association with survival and neurologic outcome. A total of 190 patients achieved ROSC and underwent echocardiography within 24 h. Of these, 83 (44%) patients had myocardial dysfunction. A total of 37 (45%) patients with myocardial dysfunction survived to discharge, 39% with intact neurologic status. History of congestive heart failure (OR 6.21; 95% CI 2.54 15.19), male gender (OR 2.27; 95% CI 1.08-4.78), witnessed arrest (OR 4.20; 95% CI 1.78-9.93), more than three doses of epinephrine (OR 6.10; 95% CI 1.12-33.14), more than four defibrillations (OR 4.7; 95% CI 1.35-16.43), longer duration of resuscitation (OR 1.06; 95% CI 1.01-1.10), and therapeutic hypothermia (OR 3.93; 95% CI 1.32-11.75) were associated with myocardial dysfunction. Cardiopulmonary resuscitation immediately initiated by healthcare personnel was associated with lower odds of myocardial dysfunction (OR 0.40; 95% CI 0.17-0.97). There was no association between early myocardial dysfunction and mortality or neurological outcome. Nearly half of OHCA patients have myocardial dysfunction. A number of clinical factors are associated with myocardial dysfunction, and may aid providers in anticipating which patients need early diagnostic evaluation and specific treatments. Early myocardial dysfunction is not associated with neurologically intact survival. PMID- 28983760 TI - Chikungunya Virus-Associated Disease. AB - PURPOSE OF REVIEW: Chikungunya virus (CHIKV) infection has become increasingly prevalent in the last decade not only across the southern hemisphere but also, because of a recently documented viral mutation, in southern Europe and the USA. With the global spread of CHIKV infection, practitioners should know its epidemiology, pathophysiology and clinical features. RECENT FINDINGS: The acute phase of CHIKV disease is characterised by a fever-arthralgia-rash syndrome. Chronic rheumatic manifestations can persist for months to years with very variable clinical presentations. Some cases mimic inflammatory rheumatism such as rheumatoid arthritis. Several risk factors for persistent joint pain, notably older age, have been identified in cohort studies. Despite a low mortality rate with CHIKV infection, the rate of disability with chronic joint symptoms is high, and effective treatments are lacking. Current research is focusing on the development of vaccines and antiviral drugs, and data on treatment of CHIKV induced chronic arthritis are needed. PMID- 28983761 TI - Brucellosis in migratory sheep flock from Maharashtra, India. AB - Brucellosis is a zoonotic disease worldwide distributed and having the economic as well as public health importance. The prevalence of brucellosis among sheep flock having history of abortions was studied. A total of 229 samples comprising of 157 blood and 72 clinical samples (vaginal swabs) were collected from 157 animals. Clinical samples were processed for the isolation of Brucella melitensis. Serum samples (n = 157) were tested by Rose Bengal plate test (RBPT) and i-ELISA. A total of 68 (43.31%) and 104 (66.24%) samples were positive by RBPT and ELISA, respectively. Brucella isolates (n = 2) were recovered from clinical samples. Both isolates demonstrated amplification for bcsp 31 and IS711 genes. On AMOS PCR, both the isolates amplified at 731 bp, i.e., belongs to B. melitensis species. The incidence of B. melitensis in a migratory flock warns the thorough testing and culling of Brucella-infected sheep from the flock on a continuous basis; otherwise, such incidence will be routine and poor farmers will be at a loss. PMID- 28983762 TI - Enhanced pyruvate production in Candida glabrata by overexpressing the CgAMD1 gene to improve acid tolerance. AB - OBJECTIVES: To enhance acid tolerance of Candida glabrata for pyruvate production by engineering AMP metabolism. RESULTS: The physiological function of AMP deaminase in AMP metabolism from C. glabrata was investigated by deleting or overexpresseing the corresponding gene, CgAMD1. At pH 4, CgAMD1 overexpression resulted in 59 and 51% increases in biomass and cell viability compared to those of wild type strain, respectively. In addition, the intracellular ATP level of strain Cgamd1Delta/CgAMD1 was down-regulated by 22%, which led to a 94% increase in pyruvate production. Further, various strengths of CgAMD1 expression cassettes were designed, thus resulting in a 59% increase in pyruvate production at pH 4. Strain Cgamd1Delta/CgAMD1 (H) was grown in a 30 l batch bioreactor at pH 4, and pyruvate reached 46.1 g/l. CONCLUSION: CgAMD1 overexpression plays an active role in improving acid tolerance and pyruvate fermentation performance of C. glabrata at pH 4. PMID- 28983763 TI - [Patients with metastatic prostate cancer : Recommendations for primary hormonal or chemohormonal therapy]. AB - The standard treatment for patients with metastatic, hormone-sensitive prostate cancer (mCSPC) has so far consisted of medical or surgical castration. However, two published clinical trials using docetaxel in combination with castration (CHAARTED and STAMPEDE) recently provided evidence for a substantial improvement in overall survival. The survival benefit was 14 and 22 months, respectively, in the two trials. In addition, the CHAARTED trial showed that patients with high volume disease may benefit most from chemohormonal treatment. According to the current available evidence, the new standard of treatment for patients therefore consists of castration in combination with docetaxel-based chemotherapy, which should be offered to all patients who are fit to receive chemotherapy. With the results of the LATITUDE and a further study-arm of the STAMPEDE trial, the combination of androgen-deprivation therapy (ADT) plus abiraterone/prednisone has recently become an alternative treatment to chemohormonal treatment. This combination leads to an identical survival benefit compared to chemohormonal treatment and is recommended by expert panels. Based on the current evidence, it is not possible to decide which patient may benefit from chemohormonal treatment and who will benefit from the combination of ADT plus abiraterone/prednisone. PMID- 28983764 TI - Effect of patient age on accuracy of primary MRI signs of long head of biceps tearing and instability in the shoulder: an MRI-arthroscopy correlation study. AB - OBJECTIVE: To determine the effect of patient age on the accuracy of primary MRI signs of long head of biceps (LHB) tendon tearing and instability in the shoulder using arthroscopy as a reference standard. MATERIALS AND METHODS: Subjects with MRI studies and subsequent arthroscopy documenting LHB tendon pathology were identified and organized into three age groups (18-40, 41-60, 61-87). Normal and tendinopathic tendons were labeled grade 0, partial tears grade 1 and full tears grade 2. Two radiologists blinded to arthroscopic data graded MRI studies independently. Prevalence of disease, MRI accuracy for outcomes of interest, and inter-reader agreement were calculated. RESULTS: Eighty-nine subjects fulfilled inclusion criteria with 36 grade 0, 36 grade 1 and 17 grade 2 tendons found at arthroscopy. MRI sensitivity, regardless of age, ranged between 67-86% for grade 0, 72-94% for grade 1 and 82-94% for grade 2 tendons. Specificity ranged between 83-96% for grade 0, 75-85% for grade 1 and 99-100% for grade 2 tendons. MRI accuracy for detection of each LHB category was calculated for each age group. MRI was found to be least sensitive for grade 0 and 1 LHB tendons in the middle aged group with sensitivity between 55-85% for grade 0 and 53-88% for grade 1 tendons. Agreement between MRI readers was moderate with an unweighted kappa statistic of 62%. CONCLUSION: MRI accuracy was moderate to excellent and agreement between MRI readers was moderate. MRI appears to be less accurate in characterizing lower grades of LHB tendon disease in middle-aged subjects. PMID- 28983765 TI - Meandering Rivers: How Important is Lateral Variability for Species Persistence? AB - Models for population dynamics in rivers and streams have highlighted the importance of spatial and temporal variations for population persistence. We present a novel model that considers the longitudinal variation as introduced by the sinuosity of a meandering river where a main channel is laterally extended to point bars in bends. These regions offer different habitat conditions for aquatic populations and therefore may enhance population persistence. Our model is a nonstandard reaction-advection-diffusion model where the domain of definition consists of the real line (representing the main channel) with periodically added intervals (representing the point bars). We give an existence and uniqueness proof for solutions of the equations. We then study population persistence as the (in-) stability of the trivial solution and population spread as the minimal wave speed of traveling periodic waves. We conduct a sensitivity analysis to highlight the importance of each parameter on the model outcome. We find that sinuosity can enhance species persistence. PMID- 28983766 TI - Hersintuzumab: A novel humanized anti-HER2 monoclonal antibody induces potent tumor growth inhibition. AB - Humanized monoclonal antibodies (mAbs) against HER2 including trastuzumab and pertuzumab are widely used to treat HER2 overexpressing metastatic breast cancers. These two mAbs recognize distinct epitopes on HER2 and their combination induces a more potent blockade of HER2 signaling than trastuzumab alone. Recently, we have reported characterization of a new chimeric mAb (c-1T0) which binds to an epitope different from that recognized by trastuzumab and significantly inhibits proliferation of HER2 overexpressing tumor cells. Here, we describe humanization of this mAb by grafting all six complementarity determining regions (CDRs) onto human variable germline genes. Humanized VH and VL sequences were synthesized and ligated to human gamma1 and kappa constant region genes using splice overlap extension (SOE) PCR. Subsequently, the humanized antibody designated hersintuzumab was expressed and characterized by ELISA, Western blot and flow cytometry. The purified humanized mAb binds to recombinant HER2 and HER2 overexpressing tumor cells with an affinity comparable with the chimeric and parental mouse mAbs. It recognizes an epitope distinct from those recognized by trastuzumab and pertuzumab. Binding of hersintuzumab to HER2 overexpressing tumor cells induces G1 cell cycle arrest, inhibition of ERK and AKT signaling pathways and growth inhibition. Moreover, hersintuzumab could induce antibody-dependent cell cytotoxicity (ADCC) on BT-474 cells. This new humanized mAb is a potentially valuable tool for single or combination breast cancer therapy. PMID- 28983767 TI - Psychiatric Management, Administration, and Leadership: a Continuum or Distinct Concepts? AB - To clarify the relationship between the concepts of management, administration, and leadership in psychiatry. The authors provide a review of the conceptual evolution of administrative psychiatry and develop operational definitions of these three domains. Based upon their experiences, they discuss relevant core competencies and personal attributes. The authors found that the terms psychiatric management, psychiatric administration, and psychiatric leadership are often used interchangeably, yet they each have a different and distinct focus. Additionally, some in the field consider the concepts overlapping, existing on a continuum, while others draw distinct conceptual boundaries between these terms. Psychiatrists in leadership positions function in all three domains. While these are distinct concepts, the authors recommend that administrative psychiatrists integrate all three in their everyday work. The authors suggest the distinctions among these concepts should inform training and identify core competencies related to these distinctions. Mentoring should focus on the practical integration of the concepts of management, administration, and leadership in administrative psychiatry. The authors present a cohesive framework for future development of a curriculum for education and research. PMID- 28983768 TI - Low-dose combined exposure of nanoparticles and heavy metal compared with PM2.5 in human myocardial AC16 cells. AB - The co-exposure toxicity mechanism of ultrafine particles and pollutants on human cardiovascular system are still unclear. In this study, the combined effects of silica nanoparticles (SiNPs) and/or carbon black nanoparticles (CBNPs) with Pb(AC)2 compared with particulate matter (PM)2.5 were investigated in human myocardial cells (AC16). Our study detected three different combinations of SiNPs and Pb(AC)2, CBNPs and Pb(AC)2, and SiNPs and CBNPs compared with PM2.5 at low dose exposure. Using PM2.5 as positive control, our results suggested that the combination of SiNPs and Pb(AC)2/CBNPs could increase the production of reactive oxygen species (ROS), lactate dehydrogenase leakage (LDH), and malondialdehyde (MDA) and decrease the activities of superoxide dismutase (SOD) and glutathione (GSH); induce inflammation by the upregulation of protein CRP and TNF-alpha, and apoptosis by the upregulation of protein caspase-3, caspase-9, and Bax while the downregulation of protein Bcl-2; and trigger G2/M phase arrest by the upregulation of protein Chk2 and downregulation of protein Cdc2 and cyclin B1. In addition, the combination of CBNPs and Pb(AC)2 induced a significant increase in MDA and reduced the activities of ROS, LDH, SOD, and GSH, with G1/S phase arrest via upregulation of Chk1 and downregulation of CDK6 and cyclin D1. Our data suggested that the additive interaction and synergistic interaction are the major interaction in co-exposure system, and PM2.5 could trigger more severe oxidative stress, G2/M arrest, and apoptosis than either co-exposure or single exposure. PMID- 28983769 TI - Temporal lobe epilepsy due to meningoencephaloceles into the greater sphenoid wing: a consequence of idiopathic intracranial hypertension? AB - PURPOSE: Antero-inferior temporal lobe meningoencephaloceles are a rare, but increasingly recognized cause of drug-resistant temporal lobe epilepsy (TLE). In order to evaluate whether these lesions are related to idiopathic intracranial hypertension (IIH), we analyzed clinical and MRI findings of a cohort of patients undergoing presurgical work-up. METHODS: Seizure onset in the anterior temporal lobe was proven by EEG electrodes in 22 patients, and in 21 patients, anterior temporal lobectomy (mostly with sparing of the hippocampus) was performed. MRI signs of IIH (in particular empty sella) and the volumes of the ventricles and external CSF spaces were determined and related to the body mass index (BMI) and clinical outcome. RESULTS: Six of seven obese (BMI > 30 kg/m2) compared to four of 15 non-obese patients had partial empty or empty sella (p = 0.007). Bilateral lesions were found in all obese and 11 patients. Seizure freedom (Engel class 1A) was achieved in 12 of 21 patients (5 obese compared to 7 non-obese patients). BMI was related to the volume of the external CSF spaces (r = 0.467), and age at seizure onset was higher in obese patients. CONCLUSION: Roughly a third of patients with temporal lobe epilepsy due to antero-inferior meningoencephaloceles is obese and has MRI signs of idiopathic intracranial hypertension. PMID- 28983770 TI - Permutation Mutual Information: A Novel Approach for Measuring Neuronal Phase Amplitude Coupling. AB - Cross-frequency phase-amplitude coupling (PAC) in neuronal oscillations network plays an important functional role in large scale neuronal communication and neuronal encoding. In the present study, a novel approach named permutation mutual information (PMI) was applied in measuring PAC. It is derived from the permutation entropy based on the mutual information theory, by which the mutual information of permutations of two time series can be evaluated. In order to verify the ability of PMI, a numerical test was performed by using both simulation data and experimental data. The performances of PMI were compared with that of two well-known methods, which were the mean vector length (MVL) and the modulation index (MI). It was found that the performance of PMI was similar to that of MI when measuring PAC intensity, but the coupling sensitivity of PMI was the highest among all these three approaches. Moreover, there was the lowest sensitivity in the MVL measurement, suggesting that MVL was a more conservative approach in detecting the existence of PAC. In addition, an ROC analysis showed that PMI performed better in measuring PAC compared to that of others. Furthermore, the experimental data, obtained from rats' hippocampal CA3 regions, were analyzed by using the three approaches. The result was essentially in line with that of the simulation performances. In a word, the results suggest that PMI is a better choice for assessing PAC under the certain conditions. PMID- 28983771 TI - Endoscopic and Imaging Predictors of Complete Pathologic Response After Chemoradiation for Esophageal Cancer. AB - PURPOSE OF REVIEW: Locally advanced esophageal cancer is frequently treated preoperatively with chemotherapy and radiation. The degree of response to this preoperative therapy varies in different patients, and a complete pathological response (pCR) has important implications in the management and prognosis of these patients. This is a review of the different modalities currently available to detect pCR and the clinical context of their use. RECENT FINDINGS: While research is still ongoing, no single technique has emerged as the modality of choice to reliably predict pCR in all patients. Studies investigating the sensitivity, specificity, and accuracy of these modalities have had promising results, but no single modality has been firmly validated as the modality if choice. The emergence of functional imaging techniques and the use of biomarkers are newer developments which need further evaluation before adoption in routine clinical practice. While no single technique reliably predicts pCR, a combination of imaging and diagnostic modalities (endoscopic appearance, biopsy, EUS, and PET/CT) may provide a better diagnostic yield rather than any of these modalities taken alone. PMID- 28983773 TI - Ipilimumab and early signs of pulmonary toxicity in patients with metastastic melanoma: a prospective observational study. AB - Ipilimumab, an immune checkpoint inhibitor, is approved for treatment metastastic melanoma and is a promising agent against other malignancies. There is some preliminary evidence from case reports that ipilimumab treatment may be associated with pulmonary side effects. However, data from prospective studies on ipilimumab-related pulmonary toxicity are still scarce. Serial spirometries and measurements of CO-diffusion capacity (DLCO) in patients with metastatic melanoma before and during treatment with ipilimumab were performed. A reduction from baseline of forced vital capacity (FVC) of >= 10%, or >= 15% of DLCO was defined as clinically meaningful and indicative for pulmonary toxicity. Of 71 patients included in this study, a clinically meaningful lung function decline was registered in 6/65 (9%), 5/44 (11%), and 9/38 (24%) patients after 3, 6, and 9 weeks of treatment initiation, respectively. Even after adjusting for age, concomitant melanoma treatment, progressive pulmonary metastases, and baseline pulmonary function values, mean +/- SD DLCO decreased significantly during follow up (-4.3% +/- 13.6% from baseline, p = 0.033). Only 7% of patients reported respiratory symptoms. Clinically manifest ipilimumab-related pneumonitis was diagnosed only in one patient (1.4%). DLCO decline maybe an early indicator of subclinical pulmonary drug toxicity. Therefore, routine pulmonary function testing including DLCO measurement during treatment might help for risk stratification to screen for ipilimumab-related pneumonitis. PMID- 28983772 TI - The impact of comorbid mental health symptoms and sex on sleep functioning in children with ADHD. AB - Children with attention-deficit/hyperactivity disorder (ADHD) display more sleep problems than their peers, but it remains unclear whether comorbid mental health symptoms [i.e., anxiety, depression, oppositional-defiant disorder (ODD)] are uniquely related to sleep functioning. It is also largely unknown whether boys and girls with ADHD differ in their sleep functioning. This study (1) examined whether boys or girls with ADHD differ in their sleep functioning, (2) evaluated comorbid symptoms as uniquely related to sleep functioning domains, and (3) explored whether sex moderated associations between comorbid symptoms and sleep. Participants were 181 children (ages 7-13; 69% male; 82% White) diagnosed with ADHD. Parents completed measures assessing their child's ADHD symptoms, comorbid symptoms, and sleep functioning. Girls had poorer sleep functioning than boys across most sleep functioning domains. Sixty percent of children met cutoff criteria for having sleep problems, though rates differed significantly between girls (75%) and boys (53%). No differences in rates of sleep problems were found between ADHD subtypes/presentations or between younger and older children. In path models including ADHD and comorbid symptom dimensions, anxiety symptoms were uniquely associated with increased bedtime resistance and sleep anxiety, ADHD hyperactive-impulsive symptoms were associated with more night wakings and more parasomnia behaviors, and ODD and depressive symptoms were associated with shorter sleep duration. Depression was also uniquely associated with increased daytime sleepiness and overall sleep problems. Sex did not moderate associations between comorbid symptoms and sleep problems. This study provides important preliminary evidence that girls with ADHD experience more sleep problems than boys with ADHD. Findings also demonstrate that the associations between comorbid symptoms and sleep functioning in children with ADHD vary based on both the specific symptoms and sleep domains examined. PMID- 28983774 TI - First molecular detection of porcine circovirus type 3 in dogs in China. AB - Porcine circovirus type 3 (PCV3) has recently been isolated from diseased pigs within the USA. The objective was to detect the presence of PCV3 in dogs. Nested polymerase chain reactions (PCR) with PCV3-specific primers for the capsid gene were used to detect PCV3 genomic DNA in serum samples from dogs (n = 44) in China. There was PCV3 DNA detected in 4 of 44 dogs [all were negative for PCV2 and canine circovirus (CanineCV)]. Based on sequence analysis, positive sequences were grouped into PCV3 genotypes. However, these isolates had close evolutionary relationships with FoxCV (KP941114) and CanineCV (JQ821392). Further investigations of the epidemiology, evolutionary biology, and pathobiology of PCV3 to dogs are warranted. PMID- 28983775 TI - Deficiency of Adenosine Deaminase 2 (DADA2), an Inherited Cause of Polyarteritis Nodosa and a Mimic of Other Systemic Rheumatologic Disorders. AB - PURPOSE OF REVIEW: A new autoinflammatory disease, deficiency of adenosine deaminase 2 (DADA2), caused by mutations in the CECR1 gene, was first reported in 2014. This review aims to update progress in defining, treating, and understanding this multi-faceted disorder. RECENT FINDINGS: DADA2 was first described in patients with systemic inflammation, mild immune deficiency, and vasculopathy manifested as recurrent stroke or polyarteritis nodosa (PAN). More than 125 patients have now been reported, and the phenotype has expanded to include children and adults presenting primarily with pure red cell aplasia (PRCA), or with antibody deficiency. Age of onset and clinical severity vary widely, even among related patients, and are not clearly related to CECR1 genotype. Inflammatory features often respond to anti-TNF agents, but marrow failure and severe immune deficiency may require hematopoietic stem cell transplantation. ADA2 is expressed and secreted by monocytes and macrophages, but its biological function and the pathogenesis of DADA2 are uncertain and will remain an important area of research. Pre-clinical investigation of ADA2 replacement therapy and CECR1-directed gene therapy are warranted, but complicated by the absence of a suitable animal model. PMID- 28983776 TI - Second primary cancer after liver transplantation in hepatocellular carcinoma: a nationwide population-based study. AB - PURPOSE: The aim of this study is to evaluate prevalence of second primary cancer (SPC) among hepatocellular carcinoma (HCC) patients after liver transplantation (LT) by using nationwide claims data from South Korea. MATERIALS AND METHODS: The nationwide cohort included patients who were diagnosed with HCC and received LT from 1 January 2010 to 31 December 2014. We analyzed frequency and standardized incidence ratios (SIRs) to estimate the risk of SPC in HCC patients after LT. RESULTS: A total of 2462 patients who were diagnosed with HCC and received LT were confirmed. Of these patients, 103 (4.2%) developed SPC after LT; the most common cancer site was lung (16.5%). Patients with HCC receiving LT had high risk of SPC [SIR 2.79, 95% confidence interval (CI) 2.27-3.38], particularly lymphoma (SIR 9.26), myeloma (SIR 10.60), and bladder cancer (SIR 7.19). The 12-, 24-, 36 , and 48-month overall survival for patients with HCC after LT was 92.7, 87.8, 84.6, and 82.1%, respectively. CONCLUSIONS: HCC patients with LT had longer life expectancy and higher risk for SPC compared with the general population. Therefore, close surveillance for SPC is important in patients with HCC receiving LT. PMID- 28983777 TI - Therapy for Chronic Myelomonocytic Leukemia in a New Era. AB - Chronic myelomonocytic leukemia (CMML) is a myeloid malignancy which shares clinical and morphologic features of myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPNs) and is classified by the WHO as an MDS/MPN. The defining feature of CMML is clonal hematopoiesis that results in peripheral monocytosis. The benefit of early treatment is currently unclear, and treatment may be held until the disease exhibits accelerated blast counts or the patient becomes symptomatic. Optimal treatments for CMML are not well defined. Conventional treatments include hydroxyurea, cytarabine, and hypomethylating agents. However, all treatment options are limited and, with the exception of allogeneic stem cell transplantation, are considered palliative. As we continue to learn about the genomics of CMML and about arising therapeutic targets and those under active clinical investigation, the future therapy of CMML will likely improve considerably. Here, we review the data available for conventional therapies and highlight emerging therapeutic strategies. PMID- 28983778 TI - Probiotics for the prevention of Hirschsprung-associated enterocolitis: a systematic review and meta-analysis. AB - BACKGROUND/PURPOSE: Hirschsprung-associated enterocolitis (HAEC) is a life threatening complication of Hirschsprung's disease. HAEC is reported to occur in 6-50% of patients preoperatively and in 2-35% postoperatively. The exact cause of HAEC is not fully understood, but disturbances of intestinal microbiota have recently been reported in patients with HAEC. In recent years, the administration of probiotics has been proposed to reduce the incidence of HAEC. We conducted a systematic review and meta-analysis to determine the effect of probiotics on postoperative HAEC. METHODS: A systematic literature search for relevant articles was performed in four databases using the combinations of following terms "probiotics", "microbiota", "enterocolitis", "Lactobacillus", "Bifidobacterium", "Saccharomyces", "Streptococcus", and "Hirschsprung disease/Hirschsprung's disease" for studies published between 2002 and 2017. The relevant cohorts of the effect of probiotics in postoperative patients were systematically searched for clinical outcomes. Odds ratio (OR) or standard mean difference (SMD) with 95% confidence intervals (CI) were calculated using standardized statistical methodology. RESULTS: The search strategy identified 1274 reports. Overall, five studies met defined inclusion criteria, reporting a total of 198 patients. Two studies were prospective multicenter randomized control trials. Lactobacillus, Bifidobacterium, Streptococcus, and Enterococcus were used as probiotics. The incidence of HAEC with/without probiotics was 22.6 and 30.5%, respectively, but this was not statistically different (OR 0.72; 95% CI 0.37-1.39; P = 0.33). CONCLUSION: This study shows that the administration of probiotics was not associated with a significant reduction in the risk of HAEC. Additional studies are required to understand more fully the role of microbiota and complex interactions that cause HAEC. With increasing knowledge of the role of microbiota in HAEC, we are likely to understand better the potential benefits of probiotics in this disease. PMID- 28983779 TI - Dependence of Friability on Tablet Mechanical Properties and a Predictive Approach for Binary Mixtures. AB - PURPOSE: To systematically assess the dependence of friability on tablet mechanical properties, compaction pressure, and tablet porosity. METHODS: Several common excipients and their mixtures exhibiting diverse mechanical properties were analyzed. Tablet elastic modulus, hardness, brittleness, porosity, and tensile strength were determined using standard techniques and then were correlated to tablet friability both individually and as a group to derive a universal model. RESULTS: Viscoelastic starch exhibits the highest friability followed by brittle excipients (mannitol, DCPA, and LM) and then ductile excipients (HPC and MCC). A reasonably accurate model for predicting pharmaceutically relevant range of friability, up to 3%, of binary mixtures is presented based on friability of individual components. In addition, a multivariate model between friability and different mechanical parameters was developed, based on which the weight loss propensity of tablets may be predicted. CONCLUSIONS: The experimental findings and predictive model are useful for expedited development and optimization of tablet formulation using a minimum amount of API. PMID- 28983780 TI - Measurement repeatability of the dynamic Scheimpflug analyzer. AB - PURPOSE: To evaluate the repeatability of corneal deformation parameters measured using a dynamic Scheimpflug analyzer and the impact of baseline clinical factors on the repeatability of each parameter. STUDY DESIGN: Retrospective, cross sectional study. METHODS: Forty-eight eyes (48 healthy subjects; mean age, 49.0 +/- 19.5 years) underwent repeated examinations with the Scheimpflug analyzer to evaluate the test-retest variability. The intraclass correlation coefficient (ICC) and repeatability coefficient as indicators of variability were computed for 35 parameters measured with the Scheimpflug analyzer. The associations between the magnitude of the test-retest variability and baseline factors, such as age, axial length (AL), intraocular pressure (IOP), and central corneal thickness (CCT), were analyzed. RESULTS: The test-retest repeatability was excellent for 22 (62.9%) of 35 parameters (ICC >= 0.75), good for seven (20%), (ICC >= 0.6), fair for four (11.4%), (ICC >= 0.4), and poor for two (5.7%) parameters (ICC < 0.4). Age was associated positively with the magnitude of variability in 13 (37.1%) parameters; measurement variability was affected significantly by AL (5 parameters, 14.3%) and CCT (7 parameters, 20%) but, except for one parameter not by IOP. CONCLUSION: Most parameters of the dynamic Scheimpflug analyzer showed favorable measurement reliability in healthy subjects. However, six parameters showed poor-to-fair repeatability. Age, AL, and CCT significantly affected the repeatability of several parameters. These results should be considered when clinicians use this device in clinical practice. PMID- 28983781 TI - The distribution of lymph node metastases and their size in colon cancer. AB - PURPOSE: The purpose of this study is to clarify the optimal extent of lymph node dissection for colon cancer by evaluating the distributions of lymph node metastases and lymph node size according to tumor location and T stage. METHODS: This study enrolled 662 patients who underwent curative resection for primary colon cancer between 2013 and 2015. Lymph node regions were classified into pericolic, intermediate, and main nodes. The short-axis diameter of each dissected lymph node was measured. The distributions of lymph node metastases and lymph node size were evaluated according to tumor location and T stage. RESULTS: In the overall cohort, the incidence of metastases in pericolic nodes located more than 5 cm but no more than 10 cm from tumor and in pericolic nodes located more than 10 cm from tumor was 3.6 and 0.2%, respectively. More than 2% of patients with >= T2 tumor had metastases in main lymph nodes, and no patients with T1 tumor had metastases in main lymph nodes. Only 0.7% of patients with T1 tumor had lymph node metastases in pericolic nodes located more than 5 cm from the tumor. Both metastatic and non-metastatic lymph node sizes were significantly larger in right-sided colon cancer than in left-sided colon cancer, and both metastatic and non-metastatic lymph node sizes were significantly larger in >= T2 tumor than in T1 tumor. CONCLUSION: It is necessary to resect 10 cm of normal bowel both proximal and distal to the tumor and to perform D3 lymph node dissection for >= T2 colon cancer. PMID- 28983784 TI - Genetic Variations of DNA Repair Genes in Breast Cancer. AB - Genetic variations in DNA repair genes may affect DNA repair capacity therefore increase risk for cancer. In our study, we evaluted the relation between DNA repair gene polymorphisms XRCC1 rs1799782, rs25487, rs25489; XPC rs2228000, rs2228001; XPD rs1799793, rs13181; XRCC3 rs861539; RAD51B rs10483813, rs1314913 and breast cancer risk for 202 Turkish cases in total, in which 102 patients with breast cancer and 100 controls. Genotyping of the DNA samples was carried out by multiplex PCR and matrix-assisted laser desorption/ionization mass spectrometry with time of flight measurement (MALDI-TOF) using Sequenom MassARRAY 4 analyzer. Genotype and allele distributions were calculated between the groups. Odds ratios (ORs) and 95% confidence intervals (CIs) were reported. rs25487 AA genotype and A allele was found to be increased in the control group (respectively, OR 0.16 95% CI 0.02-1.06, p = 0.058; OR 1.55, 95% CI 1.01-2.36, p = 0.043) and rs861539 T allele was found to be decreased in the patient group (OR 1.53, 95% CI 1.01-2.30, p = 0.049). No association with breast cancer was found for the remaining SNPs. Our findings suggest that XRCC1 rs25487 AA genotype and A allele, XRCC3 rs861539 T allele may have protective effects in breast cancer for Turkish population. PMID- 28983783 TI - mTORC1 signaling-associated protein synthesis in porcine mammary glands was regulated by the local available methionine depending on methionine sources. AB - Mechanistic target of rapamycin complex1 (mTORC1) activation and protein synthesis varied with methionine sources; however, the related mechanisms are largely unknown. Porcine mammary epithelial cells (PMEC) and mammary tissue slices (MTS) were used to test whether methionine precursors differ in providing the available methionine and thus differ in mTORC1 signaling-associated protein synthesis. PMEC with methionine deprivation for 8 h and MTS from lactating sows were cultured for 24 and 2 h, respectively, with treatment media without methionine (negative control, NC) or supplemented with 0.6 mM (for PMEC) and 0.1 mM (for MTS) of L-methionine (L-MET), D-methionine (D-MET), DL-2-hydroxy-4 (methylthio) butyric acid (HMTBA), or keto-methyl(thio)butanoic acid (KMB). The measurements included: phosphorylation of mTORC1 signaling, fractional protein synthesis rate (FSR), amino acids (AA) profile, and enzyme activities. Compared with the NC treatment, activated mTORC1 signaling as manifested by higher (P < 0.05) protein abundance of phosphorylated-S6 Kinase 1 (P-S6K1) and phosphorylated 4E-binding Protein 1 (P-4E-BP1) in PMEC and MTS, and increased protein synthesis as indicated by higher (P < 0.05) FSR in MTS occurred in L-MET and HMTBA treatments rather than in D-MET treatment. Compared with the NC treatment, methionine concentration and ratio of methionine to lysine in MTS increased (P < 0.05) in L-MET and HMTBA treatments but not in D-MET treatment, and activities of enzymes responsible for conversion of D-MET and HMTBA to keto-methionine in mammary tissues were about 10 and 50%, respectively, of that in liver. Taken together, mTORC1 signaling-associated protein synthesis in porcine mammary glands was regulated by the local available methionine depending on methionine sources. PMID- 28983782 TI - Electronic Cigarettes: Their Constituents and Potential Links to Asthma. AB - PURPOSE OF REVIEW: Vaping is gaining popularity in the USA, particularly among teens and young adults. While e-cigs are commonly represented as safer alternatives to tobacco cigarettes, little is known regarding the health effects of their short- or long-term use, especially in individuals with pre-existing respiratory diseases such as asthma. Flavored e-cig liquids (e-liquids) and e-cig aerosols contain airway irritants and toxicants that have been implicated in the pathogenesis and worsening of lung diseases. In this review, we will summarize existing data on potential health effects of components present in e-cig aerosols, such as propylene glycol, vegetable glycerin, nicotine, and flavorings, and discuss their relevance in the context of asthma. RECENT FINDINGS: Recent survey data indicate that adolescents with asthma had a higher prevalence of current e-cig use (12.4%) compared to their non-asthmatics peers (10.2%) and conveyed positive beliefs about tobacco products, especially e-cigs. Similarly, a study conducted among high school students from Ontario, Canada, indicated a greater likelihood of e-cig use in asthmatics as compared to their non-asthmatic peers. Availability of different flavorings is often cited as the main reason among youth/adolescents for trying e-cigs or switching from cigarettes to e-cigs. Occupational inhalation of some common food-safe flavoring agents is reported to cause occupational asthma and worsen asthmatic symptoms. Moreover, workplace inhalation exposures to the flavoring agent diacetyl have caused irreversible obstructive airway disease in healthy workers. Additionally, recent studies report that thermal decomposition of propylene glycol (PG) and vegetable glycerin (VG), the base constituents of e-liquids, produces reactive carbonyls, including acrolein, formaldehyde, and acetaldehyde, which have known respiratory toxicities. Furthermore, recent nicotine studies in rodents reveal that prenatal nicotine exposures lead to epigenetic reprogramming in the offspring, abnormal lung development, and multigenerational transmission of asthmatic-like symptoms. Comparisons of the toxicity and health effects of e-cigs and conventional cigarettes often focus on toxicants known to be present in cigarette smoke (CS) (i.e., formaldehyde, nitrosamines, etc.), as well as smoking-associated clinical endpoints, such as cancer, bronchitis, and chronic obstructive pulmonary disease (COPD). However, this approach disregards potential toxicity of components unique to flavored e-cigs, such as PG, VG, and the many different flavoring chemicals, which likely induce respiratory effects not usually observed in cigarette smokers. PMID- 28983786 TI - Comparison of byakujutsu (Atractylodes rhizome) and sojutsu (Atractylodes lancea rhizome) on anti-inflammatory and immunostimulative effects in vitro. AB - The Japanese Pharmacopoeia defines byakujutsu (Atractylodes rhizome) as the rhizome of Atractylodes japonica or A. macrocephala and sojutsu (Atractylodes lancea rhizome) as the rhizome of A. lancea, A. chinensis, or their interspecific hybrids. Because their pharmaceutical uses differ in traditional Japanese Kampo medicine and traditional Chinese medicine, with less apparent scientific evidence, we compared the pharmacological properties between byakujutsu and sojutsu. Crude drug specimens of byakujutsu (n = 40) and sojutsu (n = 49) obtained in markets were identified by their species using DNA profiling. Their pharmacological properties were evaluated by the inhibitory effect of a MeOH extract of the samples on nitric oxide (NO) production by lipopolysaccharide stimulated murine macrophage-like RAW264.7 cells and by the inducing effect of boiling water extract of the samples on granulocyte-colony stimulating factor (G CSF) secretion from murine normal colonic epithelial MCE301 cells. We authenticated A. macrocephala (n = 8), A. japonica (n = 35), and the hybrid between A. macrocephala and A. japonica (n = 1), and they were used as byakujutsu. We authenticated A. chinensis (n = 25), A. lancea (n = 14), and the hybrid between A. chinensis and A. lancea (n = 6), and they were used as sojutsu. The inhibitory effects of byakujutsu on NO production were significantly higher than those of sojutsu (P < 0.05). This activity of A. japonica rhizome was significantly higher than that of A. macrocephala rhizome and A. lancea rhizome (P < 0.01). The activity of A. chinensis rhizome was significantly higher than that of A. lancea rhizome (P < 0.05). The extract of A. japonica rhizome significantly induced G-CSF secretion from MCE301 cells in a concentration dependent manner. These effects of byakujutsu samples were not significantly different from those of sojutsu samples. A. japonica rhizome had significantly higher activity than A. macrocephala rhizome; however, there were no statistically significant differences among A. japonica, A. chinensis, and A. lancea. The pharmacological differences of byakujutsu and sojutsu may not be large among highly variated crude drug samples with average values, and quality control with the identification of the original plant species of byakujutsu and sojutsu may guarantee their pharmacological properties. PMID- 28983785 TI - Implications of FGF19 on sorafenib-mediated nitric oxide production in hepatocellular carcinoma cells - a short report. AB - BACKGROUND: Hepatocellular carcinoma (HCC), a primary neoplasm derived from hepatocytes, is the second leading cause of cancer mortality worldwide. Previous work has shown that fibroblast growth factor 19 (FGF19), an oncogenic driver, acts as a negative regulator of the therapeutic efficacy of the tyrosine kinase inhibitor sorafenib in HCC cells. The FGF19-mediated mechanism affecting sorafenib treatment, however, still remains to be resolved. Here, we hypothesize that the FGF19-FGFR4 axis may affect the effectiveness of sorafenib in the treatment of HCC. METHODS: FGF19 and FGFR4 cDNAs were cloned into a pcDNA3.1 vector and subsequently used for exogenous over-expression analyses. FGF19 knockdown cells were generated using a lentiviral-mediated short hairpin RNA (shRNA) methodology and FGFR4 knockout cells were generated using a CRISPR-Cas9 methodology. FGFR4 activation in HCC cells was inhibited by BLU9931. The effects of exogenous gene over-expression, expression knockdown and knockout, as well as drug efficacies in HCC cells, were validated using Western blotting. HCC cell proliferation was assessed using a CellTiter 96(r) AQueous One Solution Cell Proliferation Assay, whereas NO levels were assessed using DAF-FM DA staining in conjunction with electrochemical biosensors. RESULTS: We found that FGF19, when exogenously overexpressed, results in a reduced sorafenib-induced NO generation and a decreased proliferation of HCC cells. In contrast, we found that either FGF19 silencing or knockout of its receptor FGFR4 sensitized HCC cells to sorafenib through the induction of NO generation. Concordantly, we found that inactivation of FGFR4 by BLU9931 enhanced the sensitivity of HCC cells to sorafenib. CONCLUSION: From our data we conclude that the FGF19-FGFR4 axis may play a critical role in the effects elicited by sorafenib in HCC cells. Blocking the FGF19-FGFR4 axis may provide novel opportunities to improve the efficacy of sorafenib in the treatment of patients with HCC. PMID- 28983787 TI - Morally-Relevant Similarities and Differences Between Assisted Dying Practices in Paradigm and Non-Paradigm Circumstances: Could They Inform Regulatory Decisions? AB - There has been contentious debate over the years about whether there are morally relevant similarities and differences between the three practices of continuous deep sedation until death, physician-assisted suicide, and voluntary euthanasia. Surprisingly little academic attention has been paid to a comparison of the uses of these practices in the two types of circumstances in which they are typically performed. A comparative domains of ethics analysis methodological approach is used in the paper to compare 1) the use of the three practices in paradigm circumstances, and 2) the use of the practices in paradigm circumstances to their use in non-paradigm circumstances. The analytical outcomes suggest that a bright moral line cannot be demonstrated between any two of the practices in paradigm circumstances, and that there are significant, morally-relevant distinctions between their use in paradigm and non-paradigm circumstances. A thought experiment is employed to illustrate how these outcomes could possibly inform the decisions of hypothetical deliberators who are engaged in the collaborative development of assisted dying regulatory frameworks. PMID- 28983788 TI - Very-long-term efficacy of bioresorbable vascular scaffolds. PMID- 28983789 TI - Acute kidney injury in necrotizing enterocolitis predicts mortality. AB - BACKGROUND: Morbidity and mortality with necrotizing enterocolitis (NEC) remains a significant challenge. Acute kidney injury (AKI) has been shown to worsen survival in critically ill neonates. To our knowledge, this study is the first to evaluate the prevalence of AKI and its impact on outcomes in neonatal NEC. METHODS: We carried out a single-center retrospective chart review of all neonates treated for NEC between 2003 and 2015 (N = 181). AKI is defined as a rise in serum creatinine (SCr) from a previous trough according to neonatal modified KDIGO criteria (stage 1 = SCr rise 0.3 mg/dL or SCr 150 < 200%, stage 2 = SCr rise 200 < 300%, stage 3 = SCr rise >=300%, SCr 2.5 mg/dL or dialysis). Primary outcome was in-hospital mortality and secondary outcomes were hospital length of stay (LOS) and need for and type of surgery. RESULTS: Acute kidney injury occurred in 98 neonates (54%), with 39 stage 1 (22%), 31 stage 2 (18%), and 28 stage 3 (16%), including 5 requiring dialysis. Non-AKI and AKI groups were not statistically different in age, weight, Bell's NEC criteria, and medication exposure (vasopressors, vancomycin, gentamicin, or diuretic). Neonates with AKI had higher mortality (44% vs 25.6%, p = 0.008) and a higher chance of death (HR 2.4, CI 1.2-4.8, p = 0.009), but the effect on LOS on survivors did not reach statistical significance (79 days, interquartile range [IQR] 30-104 vs 54 days, IQR 30-92, p = 0.09). Overall, 48 (27.9%) patients required surgical intervention. CONCLUSIONS: This study shows that AKI not only occurs in over half of patients with NEC, but that it is also associated with more than a two-fold higher mortality, highlighting the importance of early recognition and potentially early intervention for AKI. PMID- 28983790 TI - Influenza Vaccination in Patients with Common Variable Immunodeficiency (CVID). AB - PURPOSE OF REVIEW: Vaccination against influenza in patients with primary antibody deficiency is recommended. Common variable immunodeficiency (CVID) is the most frequent and clinically relevant antibody deficiency disease and is by definition characterized by an impaired vaccination response. The purpose of this review is to present the current knowledge of humoral and cellular vaccine response to influenza in CVID patients. RECENT FINDINGS: Studies conducted in CVID patients demonstrated an impaired humoral response upon influenza vaccination. Data on cellular immune response are in part conflicting, with two out of three studies showing responses similar to healthy controls. Available data suggest a benefit from influenza vaccination in CVID patients. Therefore, annual influenza vaccination in patients and their close household contacts is recommended. PMID- 28983791 TI - Co-Brooding and Co-Reflection as Differential Predictors of Depressive Symptoms and Friendship Quality in Adolescents: Investigating the Moderating Role of Gender. AB - Co-rumination has been shown advantageous for friendship quality, but disadvantageous for mental health. Recently, two components have been distinguished, with co-brooding predicting increases in depressive symptoms and co-reflection decreases. The current study aimed to replicate these findings and investigated whether both components also show differential relations with friendship quality. Gender was investigated as a moderator. Path analyses were used on data of 313 adolescents aged 9-17 (50.5% girls). Co-brooding was related to more concurrent and prospective depressive symptoms in girls. Co-reflection predicted less concurrent and prospective depressive symptoms in girls and higher concurrent positive friendship quality for boys and girls. This study underscores the value of studying co-rumination components and suggests that boys and girls in this context differ in their pathways towards depression. PMID- 28983792 TI - Conduct problems trajectories and psychosocial outcomes: a systematic review and meta-analysis. AB - There is increasing evidence that youth who follow the early onset persistent (EOP), adolescent-onset (AO) and childhood-limited (CL) trajectories of conduct problems show varying patterns of health, mental health, educational, and social outcomes in adulthood. However, there has been no systematic review and meta analysis on outcomes associated with different conduct problems trajectories. We systematically reviewed the literature of longitudinal studies considering outcomes of three conduct problems trajectories: EOP, AO, and CL compared with individuals with low levels of conduct problems (low). We performed a series of meta-analyses comparing each trajectory to the low group for eight different outcomes in early adulthood or later. Thirteen studies met our inclusion criteria. Outcomes were mental health (depression), cannabis use, alcohol use, self-reported aggression, official records of antisocial behaviour, poor general health, poor education, and poor employment. Overall, EOP individuals showed significant higher risk of poor outcome followed by AO individuals, CL individuals, and finally participants in the low group. All conduct problems trajectories showed higher risk of poor psychosocial outcomes compared to the low group, but the magnitude of risk differed across trajectories, with a general trend for the EOP to perform significantly worse, followed by the AO and CL. Early intervention is recommended across domains to maximise likelihood of desistance from antisocial behaviour and improvement on several psychosocial outcomes. PMID- 28983793 TI - The impact on rural livelihoods and ecosystem services of a major relocation and settlement program: A case in Shaanxi, China. AB - China's largest-ever resettlement program is underway, aiming to restore ecosystems and lift ecosystem service providers out of the poverty trap and into sustainable livelihoods. We examine the impact of the relocation and settlement program (RSP) to date, reporting on an ecosystem services (ES) assessment and a 1400-household survey. The RSP generally achieves the goals of ES increase and livelihood restore. In biophysical terms, the RSP improves water quality, sediment retention, and carbon sequestration. In social terms, resettled households so far report transformation of livelihoods activities from traditional inefficient agricultural and forest production to non-farm activities. Increased income contributes to decrease the poverty rate and improve resettled households' living condition and standard. Meanwhile, the RSP decreases households' dependence on ES in terms of provisioning services. Difficulty and challenge also showed up subsequently after relocation. A major current challenge is to enable poorer households to move, while providing greater follow-up support to relocated households. While the program is unique to China, it illuminates widespread opportunities for addressing environmental and poverty-related concerns in a rapidly changing world. PMID- 28983794 TI - Somatic Hypermutation Defects in Common Variable Immune Deficiency. AB - Common variable immunodeficiency (CVID) is a heterogeneous disorder characterized by impaired antibody production and recurrent infections. In the last 20 years, several groups have reported that B cells from CVID patients have an impaired somatic hypermutation (SHM). The reported frequency of this defect among CVID patient cohorts is highly variable and so is the methodology used to evaluate this process. Interestingly, the low level of SHM on B cells from CVID patients has been correlated with the presence of infectious and non-infectious complications. In this review, an overview of the studies regarding SHM in CVID patients is presented. We highlight the importance of SHM studies in CVID patients as a clinical tool due to the reported association with clinical complications by several groups. We also considered SHM measurement useful to guide future investigations in order to identify genetic defects involved in the development of the disease. PMID- 28983795 TI - Drain Placement Does Not Increase Infectious Complications After Retromuscular Ventral Hernia Repair with Synthetic Mesh: an AHSQC Analysis. AB - BACKGROUND: The use of surgical drains after ventral hernia repair (VHR) remains controversial. Some have concerns of increased infectious complications; others advocate that drains reduce fluid accumulation and surgical site occurrences (SSO). The aim of our study was to investigate the impact of retromuscular drains on SSO following retromuscular VHR with synthetic mesh. METHODS: Utilizing the Americas Hernia Society Quality Collaborative, patients between January 2013 and January 2016 undergoing retromuscular VHR with synthetic mesh were assessed for the presence of a drain. Propensity score matched patients (2 drains: 1 no drain) were evaluated for 30-day rates of SSO, surgical site infections (SSI) and SSO requiring procedural intervention (SSOPI). RESULTS: Five hundred eighty-one patients were identified as having undergone open, retromuscular VHR with synthetic mesh. Four hundred eighty-one patients with drains and 100 without drains. After matching, 300 patients were compared, 200 with drain placement and 100 without. Retromuscular drains were less likely to develop a noninfectious SSO (OR, 0.33). Drain placement was not associated with SSI (OR, 1.30) or SSOPI (OR, 0.94). CONCLUSION: Drain placement after retromuscular VHR with synthetic mesh is a common practice. Based on an analysis of early outcomes, surgical drains do not increase the risk of surgical infectious complications, and may be protective against some SSOs, such as seroma formation. PMID- 28983796 TI - Effect of Feedstock Concentration on Biogas Production by Inoculating Rumen Microorganisms in Biomass Solid Waste. AB - A methane production system with continuous stirred-tank reactor, rumen liquid as inoculate microorganisms, and paper mill excess sludge (PES) as feedstock was studied. The work mainly focused on revealing the effect of feedstock concentration on the biogas production, which was seldom reported previously for the current system. The optimal fermentation conditions were found as follows: pH = 7, T = 39 +/- 1 degrees C, sludge retention time is 20 days, sludge with total solids (TS) are 1, 2, 3.5, 5, 10, and 13% in weight. Daily gas yields were measured, and biogas compositions were analyzed by gas chromatograph. Under such conditions, the optimum input TS was 10 wt%, and the biogas yield and volume gas productivity were 280.2 mL/g.TS and 1188.4 mL L-1.d-1, respectively. The proportions of CH4 and CO2 in the biogas were 65.1 and 34.2%. The CH4 yield reached 182.7 mL/g VS (volatile suspended solid), which was higher than previously reported values. The findings of this work have a significant effect on promoting the application of digesting PES by rumen microorganisms and further identified the technical parameter. PMID- 28983797 TI - Clinical factors associated with decision to recommend methylphenidate treatment for children with ADHD in France. AB - European guidelines advise on best practices for the diagnosis and non pharmacological and pharmacological treatment of attention-deficit hyperactivity disorder (ADHD). This study aimed to (1) assess whether clinician's decisions to initiate methylphenidate treatment in children diagnosed with ADHD are in accordance with European guidelines and (2) identify clinical factors associated with the decision to recommend methylphenidate prescription. 5 to 13-year-old patients with an ADHD diagnosis were consecutively evaluated in an outpatient child and adolescent psychiatry clinic in France. Patients underwent a multidisciplinary evaluation including a diagnostic interview, symptom severity assessments with parent questionnaires, and IQ testing. We compared children with (n = 105) and without (n = 55) recommended methylphenidate treatment using Student's t test or Wilcoxon Mann-Whitney test and Chi-square or Fisher's test. Multivariate logistic regression was implemented to determine the respective influence of each variable on treatment recommendation. Recommendation to initiate methylphenidate treatment was associated with (1) ADHD combined presentation, (2) co-occurring Oppositional Defiant Disorder/Conduct Disorder (ODD/CD), Developmental Coordination Disorder (DCD) and Learning Disorder (LD), (3) clinical severity and impairment indicated on parent questionnaires, and (4) reduced perceptual reasoning. Using a multivariate regression model, ADHD combined presentation [combined versus predominantly hyperactive/impulsive and unspecified OR 4.52 (1.23-16.55), p = 0.023], age [OR 1.46 (1.14-1.88), p = 0.003], ODD/CD [OR 5.53 (2.19-14.01), p < 0.001], DCD [OR 4.22 (1.70-10.48), p = 0.002], PRI [OR 0.97 (0.94-0.99), p = 0.01] were significantly associated with recommendation of methylphenidate treatment. Our results indicate that clinicians' treatment decision-making complies with European guidelines and is furthermore associated with the type and severity of ADHD symptoms but also with co-occurring disorders. PMID- 28983799 TI - B Vitamin Complex and Chemotherapy-Induced Peripheral Neuropathy. AB - PURPOSE OF REVIEW: The purpose of this mini review is to evaluate the literature on B vitamins and chemotherapy-induced peripheral neuropathy. RECENT FINDINGS: One hundred and five journal articles were evaluated and nine manuscripts were included. There was one in vitro, one was an animal and seven were human studies. The in vitro study was a safety study on vitamin B6 and oxaliplatin which was not directly related to CIPN. The animal study evaluated vitamin B3 on paclitaxel administration with positive results. The human studies varied using a vitamin B complex, vitamin B12 only and vitamin B6. Chemotherapy-induced peripheral neuropathy (CIPN) continues to plague patients and the medical fraternity. Currently, there are still no conclusive protective or treatment options. B vitamins have been found to play a role in CIPN prevention, but further studies are required to ascertain possible protection and treatment options. PMID- 28983798 TI - Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience. AB - : Rituximab is a human/murine, chimeric anti-CD20 monoclonal antibody with established efficacy, and a favorable and well-defined safety profile in patients with various CD20-expressing lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin lymphoma. Since its first approval 20 years ago, intravenously administered rituximab has revolutionized the treatment of B-cell malignancies and has become a standard component of care for follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and mantle cell lymphoma. For all of these diseases, clinical trials have demonstrated that rituximab not only prolongs the time to disease progression but also extends overall survival. Efficacy benefits have also been shown in patients with marginal zone lymphoma and in more aggressive diseases such as Burkitt lymphoma. Although the proven clinical efficacy and success of rituximab has led to the development of other anti-CD20 monoclonal antibodies in recent years (e.g., obinutuzumab, ofatumumab, veltuzumab, and ocrelizumab), rituximab is likely to maintain a position within the therapeutic armamentarium because it is well established with a long history of successful clinical use. Furthermore, a subcutaneous formulation of the drug has been approved both in the EU and in the USA for the treatment of B-cell malignancies. Using the wealth of data published on rituximab during the last two decades, we review the preclinical development of rituximab and the clinical experience gained in the treatment of hematologic B cell malignancies, with a focus on the well-established intravenous route of administration. This article is a companion paper to A. Davies, et al., which is also published in this issue. FUNDING: F. Hoffmann-La Roche Ltd., Basel, Switzerland. PMID- 28983800 TI - A potentially crucial role of the PKD1 C-terminal tail in renal prognosis. AB - BACKGROUND: Autosomal dominant polycystic disease (ADPKD) often results in renal failure. Recently, allelic influences of PKD1 mutation types on renal survival were extensively investigated. Here, we analyzed integrated influences of PKD1 mutation types and positions on renal survival. METHODS: We included 338 (82 pedigrees) and 72 (12 pedigrees) patients with PKD1 and PKD2 mutations, respectively, identified through comprehensive gene analysis of 101 probands with ADPKD. Genetic testing was performed using next-generation sequencing, long-range PCR, and multiplex ligation-dependent probe amplification. Pathogenic mutations were identified by a software package-integrated seven databases and provided access to five cloud-based computing systems. RESULTS: Mean renal survivals of carriers with PKD1 non-truncating-type mutations at positions upstream of G protein-coupled receptor proteolytic site (GPS-upstream domain), transmembrane domain, or cytoplasmic C-terminal tail (CTT) domain were 70.2, 67.0, and 50.1 years, respectively (P < 0.0001); renal survival was shorter for mutation positions closer to CTT domain, suggesting its crucial role in renal prognosis. Furthermore, in truncating-type mutations, strong inactivation is anticipated on nucleotides downstream from the mutation site, implying CTT domain inactivation irrespective of mutation site. Shorter mean renal survival was found for PKD1 truncating-type than non-truncating-type mutation carriers (P = 0.0348); mean renal survival was not different between PKD1 3'- and 5'-region truncating-type mutation carriers (P = 0.4375), but was shorter in PKD1 3'-region than in 5' region non-truncating-type mutation carriers (P = 0.0014). Variable strength of CTT domain inactivation might account for these results. CONCLUSIONS: Aforementioned findings indicate that CTT domain's crucial role in renal prognosis needs further investigation by larger studies (ClinicalTrials.gov; NCT02322385). PMID- 28983801 TI - Electronic Health Data Predict Outcomes After Aneurysmal Subarachnoid Hemorrhage. AB - BACKGROUD: Using electronic health data, we sought to identify clinical and physiological parameters that in combination predict neurologic outcomes after aneurysmal subarachnoid hemorrhage (aSAH). METHODS: We conducted a single-center retrospective cohort study of patients admitted with aSAH between 2011 and 2016. A set of 473 predictor variables was evaluated. Our outcome measure was discharge Glasgow Outcome Scale (GOS). For laboratory and physiological data, we computed the minimum, maximum, median, and variance for the first three admission days. We created a penalized logistic regression model to determine predictors of outcome and a multivariate multilevel prediction model to predict poor (GOS 1-2), intermediate (GOS 3), or good (GOS 4-5) outcomes. RESULTS: One hundred and fifty three patients met inclusion criteria; most were discharged with a GOS of 3. Multivariate analysis predictors of mortality (AUC 0.9198) included APACHE II score, Glasgow Come Scale (GCS), white blood cell (WBC) count, mean arterial pressure, variance of serum glucose, intracranial pressure (ICP), and serum sodium. Predictors of death/dependence versus independence (GOS 4-5)(AUC 0.9456) were levetiracetam, mechanical ventilation, WBC count, heart rate, ICP variance, GCS, APACHE II, and epileptiform discharges. The multiclass prediction model selected GCS, admission APACHE II, periodic discharges, lacosamide, and rebleeding as significant predictors; model performance exceeded 80% accuracy in predicting poor or good outcome and exceeded 70% accuracy for predicting intermediate outcome. CONCLUSIONS: Variance in early physiologic data can impact patient outcomes and may serve as targets for early goal-directed therapy. Electronically retrievable features such as ICP, glucose levels, and electroencephalography patterns should be considered in disease severity and risk stratification scores. PMID- 28983802 TI - Low Energy Availability in Athletes: A Review of Prevalence, Dietary Patterns, Physiological Health, and Sports Performance. AB - In a high-performance sports environment, athletes can present with low energy availability (LEA) for a variety of reasons, ranging from not consuming enough food for their specific energy requirements to disordered eating behaviors. Both male and female high-performance athletes are at risk of LEA. Longstanding LEA can cause unfavorable physiological and psychological outcomes which have the potential to impair an athlete's health and sports performance. This narrative review summarizes the prevalence of LEA and its associations with athlete health and sports performance. It is evident in the published scientific literature that the methods used to determine LEA and its associated health outcomes vary. This contributes to poor recognition of the condition and its sequelae. This review also identifies interventions designed to improve health outcomes in athletes with LEA and indicates areas which warrant further investigation. While return-to play guidelines have been developed for healthcare professionals to manage LEA in athletes, behavioral interventions to prevent the condition and manage its associated negative health and performance outcomes are required. PMID- 28983803 TI - Evaluating internal and ocular residual astigmatism in Chinese myopic children. AB - PURPOSE: To investigate the nature of internal astigmatism (IA) and ocular residual astigmatism (ORA) in Chinese myopic children and to identify factors that may influence IA and ORA. METHODS: A total of 206 eyes of 206 myopic children (97 boys and 109 girls; 10.95 +/- 2.2 years) were enrolled in this cross sectional study. Total ocular astigmatism (TOA), anterior corneal astigmatism (ACA), posterior corneal astigmatism (PCA) and total corneal astigmatism (TCA) were measured directly using either a Hartmann-Shack wavefront sensor or a Pentacam. IA and ORA were calculated by Fourier vector analyses (the definitions of IA and ORA are: IA = TOA - ACA - PCA, ORA = TOA - ACA). Spearman or Pearson correlation was adopted to detect multiple factors that may influence IA and ORA, which were then predicted by linear regressions. Modified compensation factors were applied to evaluate the inter-relationship between corneal astigmatism and ORA. RESULTS: While the mean values of IA and ORA were -0.52 DC * 94.8 degrees and -0.63 DC * 93.0 degrees , respectively, the percentage of ORA power over 1.00 D was as high as 28.64%. Full or under-compensation of ACA by ORA predominated in the enrolled subjects. The mean ORA J0 and J45 were -0.311 +/- 0.236 and -0.032 +/- 0.156 D, respectively, negatively correlated with the corresponding ACA components (J0: r = -0.276, J45: r = -0.616, p < 0.001). While age was not correlated with either IA or ORA (p > 0.1), the power of IA or ORA was correlated inversely with the axial length (IA: r = -0.193, p = 0.005; ORA: r = -0.169, p = 0.015) and positively with the spherical equivalent refraction (IA r = 0.195, p = 0.005; ORA r = 0.213, p = 0.002) and power of corneal astigmatism (IA-ACA: r = 0.302, IA-TCA: r = 0.368, ORA-ACA: r = 0.334, ORA-TCA: r = 0.293). Girls had larger IA powers than boys (0.741 +/- 0.345 D vs 0.651 +/- 0.340, p = 0.036). CONCLUSIONS: Full or under-compensation of ACA by ORA is common in Chinese myopic children, and the compensation efficiency may decrease with age. Among Chinese children with myopia, a larger ORA is more prevalent with less myopia and greater corneal astigmatism. PMID- 28983804 TI - Arrhythmogenic Cardiomyopathy: the Guilty Party in Adipogenesis. AB - Arrhythmogenic cardiomyopathy (ACM) is a genetic cardiac condition characterized by the replacement of the ventricular myocardium with fibro-fatty tissue, by arrhythmias and sudden death. Adipogenesis in ACM is considered an aberrant remodeling following myocardial loss. Which cell type(s) is (are) responsible for the adipose replacement is still matter of debate. A systematic overview of the different cells that have been, over time, considered as main players in adipose replacement is provided. The comprehension of the cellular component giving rise to arrhythmogenic cardiomyopathy substrate defects may represent both an essential tool for mechanistic studies of disease pathogenesis and a novel possible therapeutic target. PMID- 28983805 TI - Influence of Disease and Patient Characteristics on Daratumumab Exposure and Clinical Outcomes in Relapsed or Refractory Multiple Myeloma. AB - OBJECTIVE: The aim of this study was to understand the influence of disease and patient characteristics on exposure to daratumumab, an immunoglobulin Gkappa (IgGkappa) monoclonal antibody, and clinical outcomes in relapsed or refractory multiple myeloma (MM). PATIENTS AND METHODS: Baseline myeloma type, albumin levels, renal/hepatic function, age, sex, race, weight, Eastern Cooperative Oncology Group (ECOG) status, refractory status, and number of prior therapies were evaluated using data from two clinical studies-GEN501 (N = 104) and SIRIUS (N = 124). RESULTS: Daratumumab clearance was approximately 110% higher in IgG myeloma patients than non-IgG myeloma patients, leading to significantly lower exposure in IgG myeloma patients based on maximum trough serum concentrations (p < 0.0001). However, the overall response rate was similar for IgG and non-IgG myeloma patients (odds ratio 1.08, 95% confidence interval 0.54-2.17, p = 0.82). For a given exposure, the drug effect was significantly higher (approximately two times) in IgG versus non-IgG patients (p = 0.03). The influence of other patient and disease characteristics on daratumumab exposure was minimal and no significant effect on efficacy was observed (p >= 0.1). The incidences of infections and overall grade 3 or higher adverse events in subpopulations were generally consistent with that of the overall population. CONCLUSION: Due to competition with the MM-produced IgG M-protein for neonatal Fc receptor protection from clearance, IgG-based monoclonal antibodies in general may have significantly higher clearance and lower concentrations in IgG MM patients compared with non-IgG MM patients. Careful evaluation of the impact of exposure and patient and disease characteristics on safety and efficacy is warranted for all IgG-based monoclonal antibodies used in MM. PMID- 28983806 TI - A spatial evaluation of historic iron mining impacts on current impaired waters in Lake Superior's Mesabi Range. AB - This paper examines the water quality legacies of historic and current iron mining in the Mesabi Range, the most productive iron range in the history of North America, producing more than 42% of the world's iron ore in the 1950s. Between 1893 and 2016, 3.5 * 109 t of iron ore were shipped from the Mesabi Range to steel plants throughout the world. We map historic sites and quantities of iron mining, ore processing, water use, and tailings deposition within subwatershed boundaries. We then map the locations of impaired lakes within HUC 12 subwatershed boundaries within the Mesabi Range, using government datasets created for US federal Clean Water Act reporting. Comparing watersheds with and without historic mining activity, watersheds with historic mining activity currently contain a greater percentage of impaired lakes than control watersheds within the same range. These results suggest that historic iron ore mining and processing in the Mesabi Range affected water quality on a landscape scale, and these legacies persist long after the mines have closed. This paper outlines a novel spatial approach that land managers and policy makers can apply to other landscapes to assess the effects of past mining activity on watershed health. PMID- 28983807 TI - Relationship between tumor volume and quantitative values calculated using two dimensional bone scan images. AB - The bone scan index (BSI) is calculated from a whole-body bone scan image; it shows the tumor burden in bone as a percentage of total skeletal mass. It has been used to determine the prognosis and to assess treatment effects; however, little has been reported on whether the BSI calculated using a two-dimensional image can accurately evaluate the three-dimensional spread in tumor volume. We investigated the relationship between tumor volume and BSI using Monte Carlo simulation (MCS). We simulated a gamma camera and constructed a voxel phantom based on an anthropomorphic phantom computed tomography (CT) image and gamma rays emitted from each part according to technetium-99m-labeled methylene diphosphonate (99mTc-MDP) uptake (bone 1, soft tissue 0.2, tumor 2-32). We constructed bone scan images from the obtained counts and analyzed them using the BSI calculation software. The BSI increased with increased tumor uptake (two- to 32-fold). However, there was not always a significant difference between change in BSI and tumor uptake of eight times or greater than that of bone. When BSI was calculated with a tumor having an uptake of four-to-eight times higher than that of bone, the BSI was consistent with tumor volume, but decreased to about half the tumor volume when tumors were in the thoracic spine (Th-spine) segment. The BSI can be a good indicator of tumor volume in most segments, even though it is affected by the tumor's 99mTc-MDP uptake. Nevertheless, values calculated from the Th-spine should be interpreted carefully. PMID- 28983808 TI - Alcohol and Sexual Risk Behaviors Among Male Central Asian Labor Migrants and Non migrants in Kazakhstan: Implications for HIV Prevention. AB - This paper examines the association between alcohol consumption and sexual risk behaviors (unprotected sex, multiple sex partners, sex under influence of drugs or alcohol and commercial sex) in a sample of Central Asian migrant and non migrant laborers in the largest marketplace in Kazakhstan. We used data from The Silk Road Health Project, conducted from 2010 to 2013 with 1342 male migrant and non-migrant market workers. Participants were selected through respondent driven sampling at the Baraholka Market in Almaty, Kazakhstan. We used regression analyses adjusting for potential confounders to examine the relationship between alcohol consumption and sexual risk behavior. We found that hazardous drinking was associated with an increase in the odds of sex under the influence of drugs (aOR = 6.09, 95% CI 3.48, 10.65; p < .001) and purchasing commercial sex (aOR = 2.02, 95% CI 1.02, 4.02; p < .05). We identified potential targets for HIV interventions to reduce sexual risk behaviors among this key population. PMID- 28983809 TI - Temperature evolution of Trp-cage folding pathways: An analysis by dividing the probability flux field into stream tubes. AB - Owing to its small size and very fast folding rate, the Trp-cage miniprotein has become a benchmark system to study protein folding. Two folding pathways were found to be characteristic of this protein: pathway I, in which the hydrophobic collapse precedes the formation of alpha-helix, and pathway II, in which the events occur in the reverse order. At the same time, the relative contribution of these pathways at different temperatures as well as the nature of transition from one pathway to the other remain unclear. To gain insight into this issue, we employ a recently proposed hydrodynamic description of protein folding, in which the process of folding is considered as a motion of a "folding fluid" (Chekmarev et al., Phys. Rev. Lett. 100(1), 018107 2008). Using molecular dynamics simulations, we determine the field of probability fluxes of transitions in a space of collective variables and divide it into stream tubes. Each tube contains a definite fraction of the total folding flow and can be associated with a certain pathway. Specifically, three temperatures were considered, T = 285K, T = 315K, and T = 325K. We have found that as the temperature increases, the contribution of pathway I, which is approximately 90% of the total folding flow at T = 285K, decreases to approximately 10% at T = 325K, i.e., pathway II becomes dominant. At T = 315K, both pathways contribute approximately equally. All these temperatures are found below the calculated melting point, which suggests that the Trp-cage folding mechanism is determined by kinetic factors rather than thermodynamics. PMID- 28983810 TI - Dysregulation of Innate Lymphoid Cells in Common Variable Immunodeficiency. AB - Common variable immunodeficiency (CVID) is the most prevalent symptomatic primary immune deficiency. With widespread use of immunoglobulin replacement therapy, non infectious complications, such as autoimmunity, chronic intestinal inflammation, and lung disease, have replaced infections as the major cause of morbidity and mortality in this immune deficiency. The pathogenic mechanisms that underlie the development of these complications in CVID are not known; however, there have been numerous associated laboratory findings. Among the most intriguing of these associations is elevation of interferon signature genes in CVID patients with inflammatory/autoimmune complications, as a similar gene expression profile is found in systemic lupus erythematosus and other chronic inflammatory diseases. Linked with this heightened interferon signature in CVID is an expansion of circulating IFN-gamma-producing innate lymphoid cells. Innate lymphoid cells are key regulators of both protective and pathogenic immune responses that have been extensively studied in recent years. Further exploration of innate lymphoid cell biology in CVID may uncover key mechanisms underlying the development of inflammatory complications in these patients and may inspire much needed novel therapeutic approaches. PMID- 28983812 TI - The Pursuit of Excellence in Forensic Psychiatry Education. PMID- 28983811 TI - Value of three-dimensional T2-weighted turbo spin-echo imaging with tissue specific variable refocusing flip angle for 3-T magnetic resonance imaging of prostate cancer: comparison with conventional two- and three-dimensional T2 weighted turbo spin-echo imaging. AB - PURPOSE: To investigate the impact of three-dimensional (3D) T2-weighted turbo spin-echo imaging (TSE-T2WI) with tissue-specific variable refocusing flip angle (TS-VRFA) on image quality and prostate cancer (PCa) detection and extraprostatic extension (EPE) evaluation compared to 2D TSE-T2WI and conventional 3D TSE-T2WI with volume isotropic TSE acquisition (VISTA). MATERIALS AND METHODS: Image data sets of 40 patients who underwent 3-T MRI before prostatectomy, including multiplane 2D T2WI, 3D T2WI with TS-VRFA and VISTA, and diffusion-weighted images were independently evaluated by two radiologists. The detectability of PCa and EPE of each sequence was assessed using areas by the receiver operating characteristic curve (AUC) analysis. Image quality measures and contrast ratios (CR) between cancerous lesions and non-cancerous regions for each T2WI were also evaluated. RESULTS: Overall image quality of TS-VRFA was better than that of VISTA and equivalent to 2D. The highest CR was obtained with TS-VRFA (P < 0.05). For both readers, no significances were observed in detectability for PCa detection between three sequences (P > 0.05). For both readers, there were no significant differences in AUC for EPE evaluation between three sequences (P > 0.05). CONCLUSION: 3D T2 WI using TS-VRFA could potentially replace multiplane 2D T2 WI for prostate cancer diagnosis with better image quality than VISTA. PMID- 28983815 TI - The association between FABP7 serum levels with survival and neurological complications in acetaminophen-induced acute liver failure: a nested case-control study. AB - BACKGROUND: Acetaminophen (APAP)-induced acute liver failure (ALF) is associated with significant mortality due to intracranial hypertension (ICH), a result of cerebral edema (CE) and astrocyte swelling. Brain-type fatty acid-binding protein (FABP7) is a small (15 kDa) cytoplasmic protein abundantly expressed in astrocytes. The aim of this study was to determine whether serum FABP7 levels early (day 1) or late (days 3-5) level were associated with 21-day mortality and/or the presence of ICH/CE in APAP-ALF patients. METHODS: Serum samples from 198 APAP-ALF patients (nested case-control study with 99 survivors and 99 non survivors) were analyzed by ELISA methods and assessed with clinical data from the US Acute Liver Failure Study Group (ALFSG) Registry (1998-2014). RESULTS: APAP-ALF survivors had significantly lower serum FABP7 levels on admission (147.9 vs. 316.5 ng/ml, p = 0.0002) and late (87.3 vs. 286.2 ng/ml, p < 0.0001) compared with non-survivors. However, a significant association between 21-day mortality and increased serum FABP7 early [log FABP7 odds ratio (OR) 1.16, p = 0.32] and late (log FABP7 ~ OR 1.34, p = 0.21) was not detected after adjusting for significant covariates (MELD, vasopressor use). Areas under the receiver operating curve for early and late multivariable models were 0.760 and 0.892, respectively. In a second analysis, patients were grouped based on the presence (n = 46) or absence (n = 104) of ICH/CE. A significant difference in FABP7 levels between patients with or without ICH/CE at early (259.7 vs. 228.2 ng/ml, p = 0.61) and late (223.8 vs. 192.0 ng/ml, p = 0.19) time points was not identified. CONCLUSION: Serum FABP7 levels were significantly elevated at early and late time points in APAP-ALF non-survivors compared to survivors. However, significant differences in FABP7 levels by 21-day mortality were not ascertained after adjusting for significant covariates (reflecting severity of illness). Our study suggests that FABP7 may not discriminate between patients with or without intracranial complications. PMID- 28983816 TI - Recent Progress in Chronic Neutrophilic Leukemia and Atypical Chronic Myeloid Leukemia. AB - PURPOSE OF REVIEW: We reviewed recent diagnostic and therapeutic progress in chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML). We summarized recent genetic data that may guide future efforts towards implementing risk-adapted therapy based on mutational profile and improving disease control and survival of affected patients. RECENT FINDINGS: Recent genetic data in CNL and aCML prompted modifications to the World Health Organization (WHO) diagnostic criteria, which have improved our understanding of how CNL and aCML are different diseases despite sharing common findings of peripheral granulocytosis and marrow myeloid hyperplasia. The overlap of recurrently mutated genes between aCML and CMML support considering CSF3R-T618I mutated cases as a distinct entity, either as CNL or CNL with dysplasia. Ongoing preclinical and clinical studies will help to further inform the therapeutic approach to these diseases. Our understanding of CNL and aCML has greatly advanced over the last few years. This will improve clarity for the diagnosis of these diseases, provide a strategy for risk stratification, and guide risk adapted therapy. PMID- 28983818 TI - In search of an efficient strategy to monitor disease status of chronic heart failure outpatients: added value of blood biomarkers to clinical assessment. AB - INTRODUCTION: Blood biomarkers have the potential to monitor the severity of chronic heart failure (CHF). Studies correlating repeated measurements of blood biomarkers with repeatedly assessed New York Heart Association (NYHA) class over a prolonged follow-up period, and concomitantly investigating their associations with clinical endpoints, have not yet been performed. METHODS: Between 2011-2013, 263 CHF patients were included. At inclusion and subsequently every 3 months, we measured N-terminal pro-B-type natriuretic (NT-proBNP), high-sensitivity troponin T (Hs-TnT) and C-reactive protein (CRP), and assessed NYHA class. The primary endpoint comprised heart failure hospitalisation, cardiovascular mortality, cardiac transplantation or left ventricular assist device implantation. Time dependent Cox models were used. RESULTS: Mean age was 67 +/- 13 years, 72% were men and 27% were in NYHA class III-IV. We obtained 886 repeated measures (median 3 [IQR 2-5] per patient). The primary endpoint was reached in 41 patients during a median follow-up of 1.0 [0.6-1.4] year. Repeatedly measured NT-proBNP and Hs TnT were significantly associated with repeatedly assessed NYHA class, whereas CRP was not (NT-proBNP: beta [95% CI]: 1.56 [1.17-2.06]ln(ng/l) increase per point increase in NYHA class, p = 0.002; HsTNT: beta [95% CI]: 1.58 [1.21-2.07]). Serially measured NT-proBNP (HR [95% CI]:2.86 [1.73-4.73]), CRP (1.69 [1.21 2.34]) and NYHA class (2.33 [1.51-3.62]) were positively and independently associated with the primary endpoint, whereas Hs-TnT lost statistical significance after multivariable adjustment. A model containing serially measured NYHA class and NT-proBNP displayed a C-index of 0.84, while serially measured NYHA class and CRP showed a C-index of 0.82. CONCLUSION: Temporal NT-proBNP, CRP and NYHA class patterns are independently associated with adverse clinical outcome. Serially measured NT-proBNP and NYHA class are best suited for monitoring CHF outpatients. PMID- 28983820 TI - Selenoprotein K Mediates the Proliferation, Migration, and Invasion of Human Choriocarcinoma Cells by Negatively Regulating Human Chorionic Gonadotropin Expression via ERK, p38 MAPK, and Akt Signaling Pathway. AB - Selenoprotein K (SelK), a member of selenoprotein family, is identified as a single endoplasmic reticulum (ER) transmembrane protein. Although over-expression of SelK inhibits adherence and migration of human gastric cancer BGC-823 cells, the effects of SelK in human choriocarcinoma (CCA) are not well understood. In this study, the expression levels of SelK in three CCA cell lines, BeWo, JEG-3, and JAR, were examined. The effects of silencing or over-expressing SelK on expression of human chorionic gonadotropin beta subunit (beta-hCG) were detected by western blotting. The results show that the protein level of beta-hCG was reciprocally regulated by down- or up-regulation of SelK (*P < 0.05; #P < 0.05). The proliferative, migratory, and invasive capabilities of JEG-3 cells with reduced or over-expressed SelK were then tested using the cell counting kit-8 (CCK-8), wound healing, and transwell chamber assays. We found that these cellular activities were markedly increased by the loss of SelK in JEG-3 cells. Conversely, over-expressing SelK in JEG-3 cells suppressed these phenotypes. In addition, SelK expression after down- or up-regulation of beta-hCG was also measured. Surprisingly, we found that level of SelK was affected by beta-hCG (*P < 0.05; #P < 0.05). The proliferation, migration, and invasion were determined in JEG-3 cells after each over-expression and reduction of beta-hCG. The results confirmed that beta-hCG functions as a promoter of human choriocarcinoma. Furthermore, ERK/p38 MAPK and Akt signaling pathways were found to involve in these cellular functions. This work suggests that SelK may act as a tumor suppressor in human choriocarcinoma cells by negatively regulating beta-hCG expression via ERK, p38 MAPK, and Akt signaling pathways. These findings revealed that selenoprotein K may serve as a novel target for human choriocarcinoma therapy in vitro. PMID- 28983819 TI - Subcutaneous Rituximab for the Treatment of B-Cell Hematologic Malignancies: A Review of the Scientific Rationale and Clinical Development. AB - : Rituximab (MabThera(r)/Rituxan(r)), a chimeric murine/human monoclonal antibody that binds specifically to the transmembrane antigen CD20, was the first therapeutic antibody to enter clinical practice for the treatment of cancer. As monotherapy and in combination with chemotherapy, rituximab has been shown to prolong progression-free survival and, in some indications overall survival, in patients with various B-cell malignancies, while having a well-established and manageable safety profile and a wide therapeutic window. As a result, rituximab is considered to have revolutionized treatment practices for patients with B-cell malignancies. A subcutaneous (SC) formulation of rituximab has been developed, comprising the same monoclonal antibody as the originally marketed formulation [rituximab concentrate for solution for intravenous (IV) infusion], and has undergone a detailed, sequential clinical development program. This program demonstrated that, at fixed doses, rituximab SC achieves non-inferior serum trough concentrations in patients with non-Hodgkin lymphoma and chronic lymphocytic leukemia, with comparable efficacy and safety relative to the IV formulation. The added benefit of rituximab SC was demonstrated in dedicated studies showing that rituximab SC allows for simplified and shortened drug preparation and administration times resulting in a reduced treatment burden for patients as well as improved resource utilization (efficiency) at the treatment facility. The improved efficiency of delivering rituximab's benefit to patients may broaden patient access to rituximab therapy in areas with low levels of healthcare resources, including IV-chair capacity constraints. This article is a companion paper to G. Salles, et al., which is also published in this issue. FUNDING: F. Hoffmann-La Roche Ltd. PMID- 28983823 TI - Erratum to: Changes in the pneumococcal disease-related hospitalisations in Spain after the replacement of 7-valent by 13-valent conjugate vaccine. AB - The original version of this article was published online with an incorrectly arranged Table 2. Also, Figs. 1 and 2 were missing the legends. PMID- 28983822 TI - In vitro activity of micafungin against biofilms of Candida albicans, Candida glabrata, and Candida parapsilosis at different stages of maturation. AB - Candida spp. is able to form a biofilm, which is considered resistant to the majority of antifungals used in medicine. The aim of this study was to evaluate the in vitro activity of micafungin against Candida spp. biofilms at different stages of their maturation (2, 6, and 24 h). We assessed the inhibitory effect of micafungin against 78 clinical isolates of Candida spp., growing as planktonic or sessile cells, by widely recommended broth microdilution method. The in vitro effect on sessile cells viability was evaluated by colorimetric reduction assay. All examined strains were susceptible or intermediate to micafungin when growing as planktonic cells. At the early stages of biofilm maturation, from 11 (39.3%) to 20 (100%), tested strains, depending on the species, exhibited sessile minimal inhibitory concentrations (SMICs) of micafungin at <= 2 mg/L. For 24-h-old Candida spp. biofilms, from 3 (10.7%) to 20 (100%) of the tested strains displayed SMICs of micafungin at <= 2 mg/L. Our findings confirm that micafungin exhibits high potential anti-Candida-biofilm activity. However, this effect does not comprise all Candida species and strains. All strains were susceptible or intermediate to micafungin when growing as planktonic cells, but for biofilms, micafungin displays species- and strain-specific activity. Paradoxical growth of C. albicans and C. parapsilosis was observed. Antifungal susceptibility testing of Candida spp. biofilms would be the best solution, but to date, no reference method is available. The strongest antibiofilm activity of micafungin is observed at early stages of biofilm formation. Possibly, micafungin could be considered as an effective agent for prevention of biofilm-associated candidiasis, especially catheter-related candidaemia. PMID- 28983824 TI - The potential future contribution of shipping to acidification of the Baltic Sea. AB - International regulation of the emission of acidic sulphur and nitrogen oxides from commercial shipping has focused on the risks to human health, with little attention paid to the consequences for the marine environment. The introduction of stricter regulations in northern Europe has led to substantial investment in scrubbers that absorb the sulphur oxides in a counterflow of seawater. This paper examines the consequences of smokestack and scrubber release of acidic oxides in the Baltic Sea according to a range of scenarios for the coming decades. While shipping is projected to become a major source of strong acid deposition to the Baltic Sea by 2050, the long-term effect on the pH and alkalinity is projected to be significantly smaller than estimated from previous scoping studies. A significant contribution to this difference is the efficient export of surface water acidification to the North Sea on a timescale of 15-20 years. PMID- 28983825 TI - Correction to: Reoperative Bariatric Surgery: a Systematic Review of the Reasons for Surgery, Medical and Weight Loss Outcomes, and Relevant Behavioral Factors. AB - Eating and lifestyle behaviors, difficulty in embracing the required lifestyle changes, and reappearance of depressive and anxious symptoms have been associated with failure of weight loss or weight regain after primary surgeries. These aspects are further developed in the original manuscript. PMID- 28983826 TI - Streptomyces tsukubaensis as a new model for carbon repression: transcriptomic response to tacrolimus repressing carbon sources. AB - In this work, we identified glucose and glycerol as tacrolimus repressing carbon sources in the important species Streptomyces tsukubaensis. A genome-wide analysis of the transcriptomic response to glucose and glycerol additions was performed using microarray technology. The transcriptional time series obtained allowed us to compare the transcriptomic profiling of S. tsukubaensis growing under tacrolimus producing and non-producing conditions. The analysis revealed important and different metabolic changes after the additions and a lack of transcriptional activation of the fkb cluster. In addition, we detected important differences in the transcriptional response to glucose between S. tsukubaensis and the model species Streptomyces coelicolor. A number of genes encoding key players of morphological and biochemical differentiation were strongly and permanently downregulated by the carbon sources. Finally, we identified several genes showing transcriptional profiles highly correlated to that of the tacrolimus biosynthetic pathway regulator FkbN that might be potential candidates for the improvement of tacrolimus production. PMID- 28983827 TI - Drag of a Cottrell atmosphere by an edge dislocation in a smectic-A liquid crystal. AB - In a recent letter (P. Oswald et al., EPL 103, 46004 (2013)), we have shown that a smectic-A phase hardens in compression normal to the layers when the liquid crystal is doped with gold nanoparticles. This is due to the formation of Cottrell clouds nearby the core of the edge dislocations and the appearance of an additional drag force that reduces their mobility. We theoretically calculate the shape of the Cottrell cloud and the associated drag force as a function of the climb velocity of the dislocations. The main result is that the drag force depends on velocity and vanishes when the temperature tends to the smectic-A-to nematic transition temperature. The role of the diffusion anisotropy is also evaluated. PMID- 28983828 TI - Entropic segregation of short polymers to the surface of a polydisperse melt. AB - Chain ends are known to have an entropic preference for the surface of a polymer melt, which in turn is expected to cause the short chains of a polydisperse melt to segregate to the surface. Here, we examine this entropic segregation for a bidisperse melt of short and long polymers, using self-consistent field theory (SCFT). The individual polymers are modeled by discrete monomers connected by freely-jointed bonds of statistical length a , and the field is adjusted so as to produce a specified surface profile of width [Formula: see text]. Semi-analytical expressions for the excess concentration of short polymers, [Formula: see text], the integrated excess, [Formula: see text] , and the entropic effect on the surface tension, [Formula: see text], are derived and tested against the numerical SCFT. The expressions exhibit universal dependences on the molecular weight distribution with model-dependent coefficients. In general, the coefficients have to be evaluated numerically, but they can be approximated analytically once [Formula: see text]. We illustrate how this can be used to derive a simple expression for the interfacial tension between immiscible A- and B-type polydisperse homopolymers. PMID- 28983829 TI - Mechanical Ventilation During Resuscitation: How Manual Chest Compressions Affect a Ventilator's Function. AB - INTRODUCTION: Guidelines for resuscitation recommend positive-pressure ventilation with a fixed ventilation rate as provided by an automated transport ventilator during cardiopulmonary resuscitation (CPR) with a secured airway. We investigated the influence of manual chest compressions (CC) on the accuracy of ventilator presets and the quality of CC with intermittent positive-pressure ventilation (IPPV), bilevel ventilation (BiLevel), and the novel ventilation mode chest compression synchronized ventilation (CCSV) in a simulation model. METHODS: Ninety paramedics performed continuous CC for 2 min on a modified advanced life support mannequin with a realistic lung model. IPPV, BiLevel, and CCSV were applied in a randomized order. CCSV is a novel type of pressure-controlled ventilation with short insufflations synchronized with CC, which are stopped before decompression begins. The ventilator presets (tolerance range) were IPPV Vt = 450 (400-500) ml, PEEP = 0 hPa, f = 10/min; BiLevel Pinsp = 19 (17.1-20.9) hPa, PEEP = 5 hPa, f = 10/min; CCSV Pinsp = 60 (54-66) hPa, PEEP = 0 hPa, Tinsp = 205 ms, f = CC rate. Preset values were compared with the measured results. Values were defined as correct within a tolerance range. Quality of CC was evaluated using ERC guidelines (depth >50 mm, CC rate 100-120/min). RESULTS: Median (25th/75th percentiles) IPPV V t = 399 (386/411) ml, BiLevel Pinsp = 22.0 (19.7/25.6) hPa, and CCSV Pinsp = 55.2 (52.6/56.7) hPa. Relative frequency of delivering correct ventilation parameters according to ventilation mode: IPPV = 40 (0/100)% vs. BiLevel = 20 (0/100)%, p = 0.37 and vs. CCSV = 71 (50/83)%, p < 0.02. Pinsp was too high in BiLevel = 80 (0/100)% vs. CCSV = 0(0/0)%, p < 0.001. CC depth: IPPV 56 (48/63) mm, BiLevel 57 (48/63) mm, CCSV 60 (52/67) mm; CC rate: IPPV 117 (105/124)/min, BiLevel 116 (107/123)/min, CCSV 117 (107/125)/min. CONCLUSION: When compared to IPPV and BiLevel, CCSV works best with preset values, without exceeding the upper pressure preset during simulated CPR. Quality of CC is not negatively affected by any of the ventilation patterns. FUNDING: Parts of this study were supported by Weinmann Emergency Medical Technology GmbH + Co.KG. PMID- 28983830 TI - Posterior reversible encephalopathy with brainstem involvement. PMID- 28983831 TI - Associations Between Selenium Content in Hair and Kashin-Beck Disease/Keshan Disease in Children in Northwestern China: a Prospective Cohort Study. AB - The objective of this study was to investigate the relationship between selenium content in hair and the incidence of Kashin-Beck disease (KBD) and Keshan disease (KD) in China. A prospective cohort study was conducted among children aged 5-12 years with different levels of low-selenium (group 1, Se <= 110 ng/g; group 2, 110 < Se <= 150 ng/g; and group 3, 150 < Se <= 200 ng/g) or selenium-supplemented (group 4, Se > 200 ng/g) exposure. A person-years approach was used to calculate the incidence and rate of positive clinical signs. Relative risk (RR), attributable risk, and etiologic fraction were used to determine the strength of association between selenium and disease incidence. Seven new KBD cases were diagnosed during 3-year follow-up. Positive clinical signs of KBD were found in 17.78 (95% confidence interval [CI] 14.27-21.29) cases per 100 person-years in group 1, 13.28 (9.82-16.74) in group 2, 12.95 (9.34-16.56) in group 3, and 8.18 (5.50-10.85) in group 4. Compared with group 4, the RR (95% CI) of groups 1, 2, and 3 were 2.17 (1.48-3.19), 1.62 (1.07-2.47), and 1.58 (1.03-2.43), respectively. Positive clinical signs of KD were 25.90 (18.62-33.18) cases per 100 person-years in group 1, 5.66 (1.26-10.06) in group 2, 4.60 (0.20-9.00) in group 3, and 14.62 (8.54-20.69) in group 4. Compared with group 4, the RR (95% CI) were 1.77 (1.07-2.93), 0.39 (0.16-0.93), and 0.31 (0.11-0.89), respectively. In children, the onset of KBD was negatively correlated with selenium content within a certain range. However, there may be a U-shaped association between selenium content and KD in children. PMID- 28983832 TI - Correction to: Comparison of the Effect of Exercise on Late-Phase LTP of the Dentate Gyrus and CA1 of Alzheimer's Disease Model. AB - The original version of this article unfortunately does not include the second affiliating institution of Dr. Munder A. Zagaar. "Department of Pharmacy Pracce and Clinical Health Sciences, Texas Southern University, Houston, TX 77004" should have been included on the paper. PMID- 28983833 TI - Correction to: Moderate Treadmill Exercise Protects Synaptic Plasticity of the Dentate Gyrus and Related Signaling Cascade in a Rat Model of Alzheimer's Disease. AB - The original version of this article unfortunately does not include the second affiliating institution of Dr. Munder A. Zagaar. "Department of Pharmacy Pracce and Clinical Health Sciences, Texas Southern University, Houston, TX 77004" should have been included on the paper. PMID- 28983834 TI - Correction to: Prevention by Regular Exercise of Acute Sleep Deprivation-Induced Impairment of Late Phase LTP and Related Signaling Molecules in the Dentate Gyrus. AB - The original version of this article unfortunately does not include the second affiliating institution of Dr. Munder A. Zagaar. "Department of Pharmacy Pracce and Clinical Health Sciences, Texas Southern University, Houston, TX 77004" should have been included on the paper. PMID- 28983835 TI - Biomedical Big Data: New Models of Control Over Access, Use and Governance. AB - Empirical evidence suggests that while people hold the capacity to control their data in high regard, they increasingly experience a loss of control over their data in the online world. The capacity to exert control over the generation and flow of personal information is a fundamental premise to important values such as autonomy, privacy, and trust. In healthcare and clinical research this capacity is generally achieved indirectly, by agreeing to specific conditions of informational exposure. Such conditions can be openly stated in informed consent documents or be implicit in the norms of confidentiality that govern the relationships of patients and healthcare professionals. However, with medicine becoming a data-intense enterprise, informed consent and medical confidentiality, as mechanisms of control, are put under pressure. In this paper we explore emerging models of informational control in data-intense healthcare and clinical research, which can compensate for the limitations of currently available instruments. More specifically, we discuss three approaches that hold promise in increasing individual control: the emergence of data portability rights as means to control data access, new mechanisms of informed consent as tools to control data use, and finally, new participatory governance schemes that allow individuals to control their data through direct involvement in data governance. We conclude by suggesting that, despite the impression that biomedical big data diminish individual control, the synergistic effect of new data management models can in fact improve it. PMID- 28983836 TI - In Vivo Human Skin Penetration Study of Sunscreens by Confocal Raman Spectroscopy. AB - This research work mainly deals with the application of confocal Raman spectroscopic technique to study in vivo human skin penetration of sunscreen products, as there are a lot of controversies associated with their skin penetration. Healthy human volunteers were tested for penetration of two commercial sunscreen products into their volar forearm skin for a period of 2 h. Measurements were taken before and after application of these sunscreen products. All the confocal Raman spectra were pre-processed and then subjected to multivariate two-dimensional principal component analysis and classical least squares analysis to determine the skin penetration of these sunscreens in comparison to the "sunscreen product spectrum" which was considered as the control. Score plots of principal component analysis of confocal Raman spectra indicated clear separation between the spectra before and after application of sunscreen products. Loading plots showed the maximum differences in the spectral region from 1590 to 1626 cm-1 where the characteristic peak of the pure sunscreen products was observed. Classical least squares analysis has shown a significant penetration to a depth of 10 MUm in the volar forearm skin of healthy human volunteers for both these sunscreen products. The results confirm that the penetration of these tested sunscreen products was restricted to stratum corneum and also prove that confocal Raman spectroscopy is a simple, fast, nondestructive, and noninvasive semi-quantitative analytical technique for these studies. PMID- 28983837 TI - Treatment Advances in Spinal Muscular Atrophy. AB - PURPOSE OF REVIEW: Spinal muscular atrophy (SMA) is a genetic disorder of motor neurons in the anterior horns of the spinal cord and brainstem that results in muscle atrophy and weakness. SMA is an autosomal recessive disease linked to deletions of the SMN1 gene on chromosome 5q. Humans have a duplicate gene (SMN2) whose product can mitigate disease severity, leading to the variability in severity and age of onset of disease, and is therefore a target for drug development. RECENT FINDINGS: Advances in preclinical and clinical trials have paved the way for novel therapeutic options for SMA patients, including many currently in clinical trials. In 2016, the first treatment for SMA has been approved in the USA, an antisense oligonucleotide that increases full-length protein product derived from SMN2. The approval of a first treatment for SMA and the rapid advances in clinical trials provide the prospect for multiple approaches to disease modification. There are several other promising therapeutics in different stages of development, based on approaches such as neuroprotection, or gene therapy. PMID- 28983838 TI - How race affects evidence accumulation during the decision to shoot. AB - The biasing role of stereotypes is a central theme in social cognition research. For example, to understand the role of race in police officers' decisions to shoot, participants have been shown images of Black and White males and instructed to shoot only if the target is holding a gun. Findings show that Black targets are shot more frequently and more quickly than Whites. The decision to shoot has typically been modeled and understood as a signal detection process in which a sample of information is compared against a criterion, with the criterion set for Black targets being lower. We take a different approach, modeling the decision to shoot as a dynamic process in which evidence is accumulated over time until a threshold is reached. The model accounts for both the choice and response time data for both correct and incorrect decisions using a single set of parameters. Across four studies, this dynamic perspective revealed that the target's race did not create an initial bias to shoot Black targets. Instead, race impacted the rate of evidence accumulation with evidence accumulating faster to shoot for Black targets. Some participants also tended to be more cautious with Black targets, setting higher decision thresholds. Besides providing a more cohesive and richer account of the decision to shoot or not, the dynamic model suggests interventions that may address the use of race information in decisions to shoot and a means to measure their effectiveness. PMID- 28983839 TI - AKI persistence at 48 h predicts mortality in patients with acute on chronic liver failure. AB - BACKGROUND AND AIM: Management of acute kidney injury (AKI) in cirrhotics has undergone a paradigm change. We evaluated the impact of AKI persistence at 48 h on outcome in patients with acute on chronic liver failure (ACLF). METHODS: Consecutive patients with ACLF (n = 373) were prospectively followed. AKI was defined as increase in serum creatinine of 0.3 mg/dl or 1.5- to 2-fold from baseline. Persistent AKI was defined as nonresponsive AKI at 48 h with respect to admission serum creatinine. RESULTS: AKI at admission was present in 177 (47.5 %) patients. At 48 h, 73 % patients had persistent AKI and 27 % had responsive AKI. High Model for End-Stage Liver Disease (MELD) (>=26) [p, odds ratio (OR), 95 % confidence interval (CI)] [<0.001, 3.65 (2.1-3.67)], systemic inflammatory response syndrome (SIRS) [0.03, 1.6 (1.02-21.6)], and age (>=42 years) [0.03, 1.84 (1.19-2.85)] were significant predictors of AKI persistence. Persistent AKI was associated with significantly higher in-hospital mortality [p < 0.001, hazard ratio (HR) 1.7, 95 % CI 1.32-2.27]. We further found a lower cutoff for serum creatinine of 1.14 mg/dl at 48 h with better sensitivity of 61 %, specificity of 61 %, and likelihood ratio (LR+) of 1.6, correctly classifying 61 %, as against the conventional cutoff of 1.5 mg/dl with sensitivity of 37 %, specificity of 57 %, and LR+ of 3.3, correctly classifying 56 %. This new cutoff also predicted mortality with higher odds (OR 2.4, 95 % CI 1.3-4.8) as compared with the conventional cutoff (OR 2.1, 95 % CI 1.1-4.1). CONCLUSION: AKI persistence at 48 h predicts mortality better than serum creatinine of 1.5 mg/dl in patients with ACLF. Serum creatinine value of 1.14 mg/dl and smaller increases in its value should be considered for risk stratification of patients with ACLF for interventional strategies. PMID- 28983840 TI - Does perfectionism in bipolar disorder pedigrees mediate associations between anxiety/stress and mood symptoms? AB - BACKGROUND: Bipolar disorder (BD) and the anxiety disorders are highly comorbid. The present study sought to examine perfectionism and goal attainment values as potential mechanisms of known associations between anxiety, stress and BD symptomatology. Measures of perfectionism and goal attainment values were administered to 269 members of BD pedigrees, alongside measures of anxiety and stress, and BD mood symptoms. Regression analyses were used to determine whether perfectionism and goal attainment values were related to depressive and (hypo)manic symptoms; planned mediation models were then used to test the potential for perfectionism to mediate associations between anxiety/stress and BD symptoms. RESULTS: Self-oriented perfectionism was associated with chronic depressive symptoms; socially-prescribed perfectionism was associated with chronic (hypo)manic symptoms. Self-oriented perfectionism mediated relationships between anxiety/stress and chronic depressive symptoms even after controlling for chronic hypomanic symptoms. Similarly, socially-prescribed perfectionism mediated associations between anxiety/stress and chronic hypomanic symptoms after controlling for chronic depressive symptoms. Goal attainment beliefs were not uniquely associated with chronic depressive or (hypo)manic symptoms. CONCLUSIONS: Cognitive styles of perfectionism may explain the co-occurrence of anxiety and stress symptoms and BD symptoms. Psychological interventions for anxiety and stress symptoms in BD might therefore address perfectionism in attempt to reduce depression and (hypo)manic symptoms in addition to appropriate pharmacotherapy. PMID- 28983841 TI - Evidence-based concepts for prevention of knee and ACL injuries. 2017 guidelines of the ligament committee of the German Knee Society (DKG). AB - INTRODUCTION: Knee injuries and especially anterior cruciate ligament (ACL) tears are frequent in athletes. Therefore, primary and secondary prevention of sports related lower limb injuries is an ongoing topic of interest. The aim of present study was to establish guidelines for the prevention of knee and ACL injuries on the basis of evidence-based concepts represented in current literature. METHODS: A comprehensive literature review regarding prevention programs for knee and ACL injuries was conducted. RESULTS: Several modifiable and non-modifiable risk factors for knee injuries in athletes have been reported in literature. Referring to the ACL, specific injury mechanisms have been identified and are well understood. In particular, it has been demonstrated that dynamic valgus is one of the most important modifiable risk factors. Simple tests like the drop jump test have shown their efficacy in screening and detecting athletes at risk. There is only few evidence for the preventive effect on knee and ACL injuries by single exercises. However, in order to prevent or correct endangering movement patterns including dynamic valgus, several complex prevention programs have been developed in the past. These prevention programs are included in standard warm-up exercises and are focusing on muscle strength, balance, and proprioception, as well as running and flexibility. It is reported that these training programs can reduce the incidence of knee injuries by up to 27% and ACL injuries by up to 51%. CONCLUSIONS: Screening, identification, and correction of endangering movement patterns like the dynamic valgus are the first crucial steps in order to prevent knee and ACL injuries in athletes. Furthermore, jumping, running and flexibility exercises as well as balance and strength training are proven to reduce the incidence of these injuries and should, therefore, be integrated into the regular warm up program. Appropriate complete prevention programs are freely accessible via the Internet and should be adapted to the specific sport disciplines. PMID- 28983842 TI - Soluble Amyloid Precursor Protein Alpha Interacts with alpha3-Na, K-ATPAse to Induce Axonal Outgrowth but Not Neuroprotection: Evidence for Distinct Mechanisms Underlying these Properties. AB - Amyloid precursor protein (APP) is cleaved not only to generate the amyloid peptide (Abeta), involved in neurodegenerative processes, but can also be metabolized by alpha secretase to produce and release soluble N-terminal APP (sAPPalpha), which has many properties including the induction of axonal elongation and neuroprotection. The mechanisms underlying the properties of sAPPalpha are not known. Here, we used proteomic analysis of mouse cortico hippocampal membranes to identify the neuronal specific alpha3 (alpha3)-subunit of the plasma membrane enzyme Na, K-ATPase (NKA) as a new binding partner of sAPPalpha. We showed that sAPPalpha recruits very rapidly clusters of alpha3-NKA at neuronal surface, and its binding triggers a cascade of events promoting sAPPalpha-induced axonal outgrowth. The binding of sAPPalpha with alpha3-NKA was not observed for sAPPalpha-induced Abeta1-42 oligomers neuroprotection, neither the downstream events particularly the interaction of sAPPalpha with APP before endocytosis, ERK signaling, and the translocation of SET from the nucleus to the plasma membrane. These data suggest that the mechanisms of the axonal growth promoting and neuroprotective properties of sAPPalpha appear to be specific and independent. The signals at the cell surface specific to trigger these mechanisms require further study. PMID- 28983843 TI - AZI23'UTR Is a New SLC6A3 Downregulator Associated with an Epistatic Protection Against Substance Use Disorders. AB - Regulated activity of SLC6A3, which encodes the human dopamine transporter (DAT), contributes to diseases such as substance abuse disorders (SUDs); however, the exact transcription mechanism remains poorly understood. Here, we used a common genetic variant of the gene, intron 1 DNP1B sequence, as bait to screen and clone a new transcriptional activity, AZI23'UTR, for SLC6A3. AZI23'UTR is a 3' untranslated region (3'UTR) of the human 5-Azacytidine Induced 2 gene (AZI2) but appeared to be transcribed independently of AZI2. Found to be present in both human cell nuclei and dopamine neurons, this RNA was shown to downregulate promoter activity through a variant-dependent mechanism in vitro. Both reduced RNA density ratio of AZI23'UTR/AZI2 and increased DAT mRNA levels were found in ethanol-naive alcohol-preferring rats. Secondary analysis of dbGaP GWAS datasets (Genome-Wide Association Studies based on the database of Genotypes and Phenotypes) revealed significant interactions between regions upstream of AZI23'UTR and SLC6A3 in SUDs. Jointly, our data suggest that AZI23'UTR confers variant-dependent transcriptional regulation of SLC6A3, a potential risk factor for SUDs. PMID- 28983844 TI - The Role of Vildagliptin in the Therapy of Type 2 Diabetic Patients with Renal Dysfunction. AB - Diabetes is the leading cause of chronic kidney disease, and even in the absence of albuminuria, decreased renal function in type 2 diabetes mellitus (T2DM) patients increases the risk for major adverse cardiovascular events and death. The evidence derived from recent studies suggests that intensive glucose control not only reduces the risk for microalbuminuria and macroalbuminuria but may also decrease the rate of decline of glomerular filtration rate (GFR). Although insulin therapy is widely used in patients with T2DM and renal disease, metabolic control is particularly difficult to achieve and manage because of the limited therapeutic options and the frequent comorbidities seen in this population. Recent evidence suggests that dipeptidyl peptidase-4 (DPP-4) inhibitors may offer a better choice for improving glycemic control in T2DM patients with low GFR. This review will focus on vildagliptin, a DPP-4 inhibitor with a large body of evidence in patients with moderate to severe renal failure and a good clinical profile in terms of efficacy and safety. In particular, vildagliptin, with appropriate dose adjustment, provides clinically important reductions in glycated hemoglobin, without increasing weight and the risk of hypoglycemia even in patients with severe chronic kidney disease. PMID- 28983845 TI - Correction to: Oxidizable Phenolic Concentrations Do Not Affect Development and Survival of Paropsis Atomaria Larvae Eating Eucalyptus Foliage. AB - Ian Wallis was inadvertently omitted as an author in this study. Ian Wallis assisted with the collection of the leaf samples that were used in this study, and built the chambers that the insects were housed in. PMID- 28983847 TI - Characterizing spatiotemporal variations of chromophoric dissolved organic matter in headwater catchment of a key drinking water source in China. AB - Natural surface drinking water sources with the increasing chromophoric dissolved organic matter (CDOM) have profound influences on the aquatic environment and drinking water safety. Here, this study investigated the spatiotemporal variations of CDOM in Fengshuba Reservoir and its catchments in China. Twenty four surface water samples, 45 water samples (including surface water, middle water, and bottom water), and 15 pore water samples were collected from rivers, reservoir, and sediment of the reservoir, respectively. Then, three fluorescent components, namely two humic-like components (C1 and C2) and a tryptophan-like component (C3), were identified from the excitation-emission matrix coupled with parallel factor analysis (EEM-PARAFAC) for all samples. For spatial distributions, the levels of CDOM and two humic-like components in the reservoir were significantly lower than those in the upstream rivers (p < 0.01), indicating that the reservoir may act as a reactor to partly reduce the levels of exogenous input including CDOM and humic-like matters from the surrounding catchment. For temporal variations, the mean levels of CDOM and three fluorescent components did not significantly change in rivers, suggesting that perennial anthropic activity maybe an important factor impacting the concentration and composition of river CDOM but not the precipitation and runoff. However, these mean values of CDOM for the bulk waters of the reservoir changed markedly along with seasonal variations, indicating that the hydrological processes in the reservoir could control the quality and quantity of CDOM. The different correlations between the fluorescent components and primary water parameters in the river, reservoir, and pore water samples further suggest that the reservoir is an important factor regulating the migration and transformation of FDOM along with the variations of different environmental gradients. PMID- 28983846 TI - Microglial Activation Results in Inhibition of TGF-beta-Regulated Gene Expression. AB - Chronic inflammation mediated by persistent microglial activation is associated with the pathogenesis of neurodegenerative diseases. The mechanisms underlying chronic microglial activation are poorly understood. We have previously shown that anti-inflammatory TGF-beta signaling is inhibited in LPS-treated microglia. In this study, we assessed whether different disease-related microglial activators could downregulate TGF-beta induction of gene expression. We examined the effects of amyloid beta (Abeta) (1-42)- or heat-killed Listeria monocytogenes (HKLM) on the TGF-beta-regulated gene expression in primary rat microglia. We found that Abeta (1-42) oligomers and HKLM, in addition to LPS, suppressed TGF beta-mediated induction of gene expression in part through reducing expression of TbetaR1 mRNA encoding the TGF-beta receptor 1 in primary microglia. Abeta (1-42) and LPS also prevented induction of TGF-beta-induced genes in primary microglia. Additionally, Abeta (1-42) rescued primary microglia from TGF-beta-mediated cell death without increasing cell proliferation. Blockage of NFkappaB signaling, but not the ERK or IRF3 pathways, inhibited Abeta (1-42)- and LPS-mediated reduction of TbetaR1 mRNA. Finally, LPS and Abeta (1-42) induced transient upregulation of mRNAs encoding SnoN and Bambi, inhibitors of TGF-beta signaling. Our data indicate that one mechanism through which activators may prolong microglial stimulation is through direct inhibition of anti-inflammatory signaling. A more detailed understanding of the interaction between inflammatory and anti inflammatory pathways may reveal potential targets for ameliorating chronic inflammation and hence speed the development of therapeutics to address neurodegenerative diseases. PMID- 28983848 TI - Prevalence of HIV-1 pre-treatment drug resistance in a southern province of Iran, 2016-2017. AB - HIV-1 transmitted drug resistance (TDR) occurs when primary viruses bear drug resistance mutations (DRMs). TDR causes first-line antiretroviral (ARV) therapy (ART) failure and is becoming more pronounced due to the widespread use of ART. With the absence of routine individual-level drug resistance testing, the World Health Organization (WHO) recommends the tracking of TDR mutations and optimizing the first-line ART following pre-treatment drug resistance (PDR) surveys. Here, we report the PDR frequency for the first time in Hormozgan, a southern province of Iran. In this study, 41 blood samples from HIV-1-positive ART-candidate volunteers were collected across the province between April 2016 and March 2017. Phylogenetic analysis of the sequenced protease (PR) and reverse transcriptase (RT) regions showed that 39 out of 41 samples (95%) were CRF35_AD and the two remaining cases were subtype B (2.5%) and C (2.5%). D67G (2.4%), a mutation that reduces susceptibility to nucleoside reverse transcriptase inhibitors (NRTIs) was the only detectable TDR mutation in this population. Two other DRMs, including E138A (9.7%) and V179T (4.9%), which confer resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs), were also identified. Although no major protease inhibitor (PI) resistance mutations were detected, the minor mutations L10F and L33F (2.5% each) as well as several highly frequent polymorphic mutations were identified. Our results show a PDR frequency of 17% in infected individuals from Hormozgan, classified further as 2.4% NRTIs and 14.6% NNRTIs. These results suggest that first-line ART should be practiced carefully in Hormozgan province, and alternative regimens may become necessary for all starters. PMID- 28983849 TI - Improved Oral Bioavailability and Liver Targeting of Sorafenib Solid Lipid Nanoparticles in Rats. AB - Minimal information is available on the oral bioavailability and liver-targeting properties of sorafenib solid lipid nanoparticles (SRF-SLNs) in rats. In this study, SRF-SLNs were prepared via the combined methods of high-speed shearing and ultrasonic treatment. SRF-SLN formulations were also optimized. Particle size, zeta potential, entrapment efficiency (EE), and drug loading (DL) were used as indices for the evaluation of the as-prepared SRF-SLNs. SRF concentration was determined by the high-performance liquid chromatography method. Results showed that the average EE and DL of SRF-SLNs were 89.87 and 5.39%. The average particle size, polydispersity index, and zeta potential of SRF-SLNs were 77.16 nm, 0.28, and - 18.1 mV, respectively. The results of the stability test showed that SRF SLNs remained stable for more than 1 month at room temperature. After oral administration to rats (7.5 mg/kg), the liver-targeting evaluation results showed that the average drug selectivity index value of SRF-SLNs was 2.20 times higher, than that of the SRF-suspension. Furthermore, the area under the concentration time curve of SRF increased by 66.7% in the SRF-SLN group comparing with that in the SRF-suspension. Our results suggested that SLNs were a promising approach for the oral delivery of SRF. PMID- 28983851 TI - A Deep-Learning System for Fully-Automated Peripherally Inserted Central Catheter (PICC) Tip Detection. AB - A peripherally inserted central catheter (PICC) is a thin catheter that is inserted via arm veins and threaded near the heart, providing intravenous access. The final catheter tip position is always confirmed on a chest radiograph (CXR) immediately after insertion since malpositioned PICCs can cause potentially life threatening complications. Although radiologists interpret PICC tip location with high accuracy, delays in interpretation can be significant. In this study, we proposed a fully-automated, deep-learning system with a cascading segmentation AI system containing two fully convolutional neural networks for detecting a PICC line and its tip location. A preprocessing module performed image quality and dimension normalization, and a post-processing module found the PICC tip accurately by pruning false positives. Our best model, trained on 400 training cases and selectively tuned on 50 validation cases, obtained absolute distances from ground truth with a mean of 3.10 mm, a standard deviation of 2.03 mm, and a root mean squares error (RMSE) of 3.71 mm on 150 held-out test cases. This system could help speed confirmation of PICC position and further be generalized to include other types of vascular access and therapeutic support devices. PMID- 28983850 TI - Topical Administration of Ibuprofen for Injured Athletes: Considerations, Formulations, and Comparison to Oral Delivery. AB - Non-steroidal anti-inflammatory drugs (NSAIDs) are a class of drugs commonly used to treat both the acute and chronic injuries sustained by athletes during training and competition. In many parts of the world, NSAIDs can be purchased over-the-counter and used without any physician oversight. However, the chronic nature of overuse injuries requires NSAIDs to be taken orally for an extended period of time. As a result, they can have significant adverse effects on athletes, namely gastrointestinal (GI), renal, and cardiovascular damage. Dyspepsia and upper GI ulceration and bleeding are of great concern in chronic NSAID use, and as such oral NSAIDs are generally contraindicated in those with a history of peptic ulcers or irritable bowel disease. In the setting of chronic overuse soft tissue or joint disease, topically administered NSAIDs offer an alternate route of administration that has the potential to deliver a similar level of pain and anti-inflammatory relief while bypassing the harmful side effects associated with oral intake. Topically applied NSAIDs are able to achieve high concentrations within the targeted site of action while simultaneously keeping plasma concentrations low, offering several advantages over oral administration. One commonly used generic NSAID is ibuprofen (2-(4 isobutylphenyl)propanoic acid). First synthesized in the 1960s, ibuprofen has since become widely available as an over-the-counter pharmaceutical. In this review, we outline new and different techniques that have been used to deliver ibuprofen into diseased tissues, including supersaturations, microemulsions, gels, nanosystems, and microneedles. We also review relevant clinical trials comparing transdermally delivered ibuprofen to placebo and orally administered ibuprofen. PMID- 28983852 TI - Autism spectrum disorder and Li-Fraumeni syndrome: purely coincidental or mechanistically associated? AB - BACKGROUND: Autism spectrum disorders (ASDs) are neurodevelopmental disorders with impaired social interactions and communication and restrictive, repetitive patterns of behaviors, interests, and activities. A recent epidemiological study suggests that children with ASD might have an increased cancer risk. CASE PRESENTATION: The 14.5-year-old boy, previously diagnosed with ASD, was referred with persistent bone pain. Diagnostic work-up confirmed diagnosis of acute lymphoblastic leukemia (ALL); cytogenetic analysis revealed low hypodiploid karyotype with a mutation (c.733G>A, p.Gly245Ser, rs28934575) in TP53 in the leukemic blasts. By Sanger sequencing, the presence of this mutation in the germline was subsequently confirmed and, thus, diagnosis of Li-Fraumeni syndrome (LFS) was made. His family history was remarkable with two siblings with intellectual disability and a mother who has died of premenopausal breast cancer. CONCLUSIONS: Some of the oncogenes and tumor suppressor genes causing cancer susceptibility syndromes overlap with those involved in autism. This functional overlap between autism and cancer is novel and particularly compelling. The surprising coincidence of LFS and ASD in our patient raises the question whether this is purely coincidental or mechanistically associated. PMID- 28983854 TI - A Pilot Study Examining Factors Influencing Readiness to Progress to Indirect Supervision Among First Year Residents in a General Psychiatry Training Program. AB - OBJECTIVE: In the first year of training, psychiatry residents progress from direct supervision to indirect supervision but factors predicting time to transition between these levels of supervision are unknown. This study aimed to examine times for transition to indirect levels of supervision and to identify resident factors associated with slower progression. METHODS: The authors compiled data from training files from years 2011-2015, including licensing exam scores, age, gender, medical school, month of first inpatient psychiatry rotation, and transition times between levels of supervision. Correlational analysis examined the relationship between these factors. Univariate analysis further examined the relationship between medical school training and transition times between supervision levels. RESULTS: Among the factors studied, only international medical school training was positively correlated with time to transition to indirect supervision and between levels of indirect supervision. CONCLUSIONS: International medical graduate (IMG) interns in psychiatry training may benefit from additional training and support to reach competencies required for the transition to indirect supervision. PMID- 28983853 TI - The effect of pericardial incision on right ventricular systolic function: a prospective observational study. AB - BACKGROUND: Echocardiographic longitudinal markers of right ventricular (RV) systolic function are commonly depressed after coronary artery bypass graft surgery (CABG) despite an uncomplicated course and good clinical recovery. The exact timing and cause of these changes is unknown. The aim of this observational study was to monitor echocardiographic markers of RV systolic function intraoperatively during CABG. We used angle-independent speckle tracking to measure the primary endpoints of tricuspid annular plane systolic excursion (TAPSE) and tricuspid annular systolic velocity (S') before and after pericardiotomy. METHODS: Twenty-four patients undergoing elective on-pump CABG were enrolled in the study. Speckle tracking-derived TAPSE, S', free wall systolic strain, RV outflow tract strain, colour tissue Doppler-derived isovolumic acceleration (IVA) and two-dimensional RV dimensions and fractional area change (FAC) were measured at three intraoperative time points: 1) after sternotomy immediately prior to pericardiotomy; 2) after pericardiotomy and placement of pericardial retraction sutures; and 3) following cardiopulmonary bypass after chest closure. RESULTS: Adequate image quality to perform speckle tracking measurements was obtained in twenty-one patients. We found that there were no significant changes to echocardiographic parameters of RV systolic function between pre- and post-pericardiotomy. The mean (SD) of the primary endpoints were: TAPSE [28.1 (5.1) mm vs 27.7 (7.4) mm, respectively; mean difference, -0.4 mm; 97.5% confidence interval (CI), -4.0 to 3.1; P = 0.76] and S' [10.4 (2.1) cm.sec-1 vs 10.8 (1.9) cm.sec-1, respectively; mean difference, 0.4 cm.sec-1; 97.5% CI, -0.9 to 1.7; P = 0.48]. Significant reductions in the parameters of RV systolic function were found only after cardiopulmonary bypass and chest closure. CONCLUSION: Pericardial opening and suspension had no significant effect on the indices of RV systolic function derived from speckle tracking or colour tissue Doppler. PMID- 28983855 TI - Incorporating Measurement Error from Modeled Air Pollution Exposures into Epidemiological Analyses. AB - PURPOSE OF REVIEW: Outdoor air pollution exposures used in epidemiological studies are commonly predicted from spatiotemporal models incorporating limited measurements, temporal factors, geographic information system variables, and/or satellite data. Measurement error in these exposure estimates leads to imprecise estimation of health effects and their standard errors. We reviewed methods for measurement error correction that have been applied in epidemiological studies that use model-derived air pollution data. RECENT FINDINGS: We identified seven cohort studies and one panel study that have employed measurement error correction methods. These methods included regression calibration, risk set regression calibration, regression calibration with instrumental variables, the simulation extrapolation approach (SIMEX), and methods under the non-parametric or parameter bootstrap. Corrections resulted in small increases in the absolute magnitude of the health effect estimate and its standard error under most scenarios. Limited application of measurement error correction methods in air pollution studies may be attributed to the absence of exposure validation data and the methodological complexity of the proposed methods. Future epidemiological studies should consider in their design phase the requirements for the measurement error correction method to be later applied, while methodological advances are needed under the multi-pollutants setting. PMID- 28983856 TI - Effect of HHH-Therapy on Regional CBF after Severe Subarachnoid Hemorrhage Studied by Bedside Xenon-Enhanced CT. AB - BACKGROUND: Management of delayed cerebral ischemia (DCI) following subarachnoid hemorrhage (SAH) is difficult and still carries controversies. In this study, the effect of therapeutic hypervolemia, hemodilution, and hypertension (HHH-therapy) on cerebral blood flow (CBF) was assessed by xenon-enhanced computerized tomography (XeCT) hypothesizing an increase in CBF in poorly perfused regions. METHODS: Bedside XeCT measurements of regional CBF in mechanically ventilated SAH patients were routinely scheduled for day 0-3, 4-7, and 8-12. At clinical suspicion of DCI, patients received 5-day HHH-therapy. For inclusion, XeCT was required at 0-48 h before start of HHH (baseline) and during therapy. Data from corresponding time-windows were also collected for non-DCI patients. RESULTS: Twenty patients who later developed DCI were included, and twenty-eight patients without DCI were identified for comparison. During HHH, there was a slight nonsignificant increase in systolic blood pressure (SBP) and a significant reduction in hematocrit. Median global cortical CBF for the DCI group increased from 29.5 (IQR 24.6-33.9) to 38.4 (IQR 27.0-41.2) ml/100 g/min (P = 0.001). There was a concomitant increase in regional CBF of the worst vascular territories, and the proportion of area with blood flow below 20 ml/100 g/min was significantly reduced. Non-DCI patients showed higher CBF at baseline, and no significant change over time. CONCLUSIONS: HHH-therapy appeared to increase global and regional CBF in DCI patients. The increase in SBP was small, while the decrease in hematocrit was more pronounced, which may suggest that intravascular volume status and rheological effects are of importance. XeCT may be potentially helpful in managing poor-grade SAH patients. PMID- 28983857 TI - Tolerability and Effectiveness of Exenatide Once Weekly Relative to Basal Insulin Among Type 2 Diabetes Patients of Different Races in Routine Care. AB - INTRODUCTION: Analyses of efficacy and tolerability of pharmacologic interventions are based on clinical trials that often include predominately white populations, in part because of challenges associated with recruitment and retention of racial/ethnically diverse study populations. Using real-world electronic health record (EHR) data, we sought to evaluate the tolerability and effectiveness of exenatide once weekly (EQW), overall and relative to basal insulin (BI), according to race. METHODS: Patients with type 2 diabetes initiating EQW or BI between 2012 and 2015 were selected from the Optum EHR Research Database, a system pooling data from dozens of hospitals throughout the US. Measures of HbA1c, weight, and body mass index (BMI) were summarized at initiation and quarterly in the first year afterwards. Occurrences of gastrointestinal (GI) symptoms and hypoglycemia were identified by diagnostic codes and clinical notes, and incidence rates (IR) and relative rates (RR) were calculated. RESULTS: Overall, 4907 white patients (mean age = 57 years) and 454 African American patients (mean age = 53 years) were included. The percent change in HbA1c from initiation through 9-12 months was similar for white and African American patients [EQW-White: -6.89 (95% CI: -8.29, -5.50), EQW-African American: -5.99 (95% CI: -10.33, -1.65), BI-White: -4.68 (95% CI: -5.51, -3.86), BI-African American: -3.11 (95% CI: -5.37, -0.85)]. For EQW, percent change in weight was 1.73 (95% CI: -2.45, -1.02) for white patients and -1.11 (95% CI: -3.02, -0.81) for African American patients. No weight loss was observed among BI initiators. Relative to BI initiators, EQW initiators had lower rates of hypoglycemia [White RR: 0.82 (95% CI: 0.66, 1.01), African American RR: 0.59 (95% CI: 0.26, 1.34)]. GI symptoms were increased in white EQW initiators. CONCLUSIONS: Treatment with EQW, relative to BI, was associated with larger reductions in HbA1c and weight and reduced risk of hypoglycemia, effects that were not different for white and African American patients. FUNDING: AstraZeneca, Gothenburg, Sweden. PMID- 28983858 TI - CME INSTRUCTIONS: Cardiac Autonomic Innervation. PMID- 28983859 TI - Provider perceptions on procalcitonin testing: a survey to tailor facility implementation. PMID- 28983860 TI - Evidence for spontaneous serial refreshing in verbal working memory? AB - Working memory (WM) keeps information temporarily accessible for ongoing cognition. One proposed mechanism to keep information active in WM is refreshing. This mechanism is assumed to operate by bringing memory items into the focus of attention, thereby serially refreshing the content of WM. We report two experiments in which we examine evidence for the spontaneous occurrence of serial refreshing in verbal WM. Participants had to remember series of red letters, while black probe letters were presented between these memory items, with each probe to be judged present in or absent from the list presented so far, as quickly as possible (i.e., the probe-span task). Response times to the probes were used to infer the status of the representations in WM and, in particular, to examine whether the content of the focus of attention changed over time, as would be expected if serial refreshing occurs spontaneously during inter-item pauses. In sharp contrast with this hypothesis, our results indicate that the last presented memory item remained in the focus of attention during the inter-item pauses of the probe-span task. We discuss how these findings help to define the boundary conditions of spontaneous refreshing of verbal material in WM, and discuss implications for verbal WM maintenance and forgetting. PMID- 28983861 TI - The Issues of Freedom and Happiness in Moral Bioenhancement: Continuing the Debate With a Reply to Harris Wiseman. AB - During the previous years, Harris Wiseman has devoted substantial attention to my stance on voluntary moral bioenhancement. He argued that he has been influenced by that position, but nonetheless criticized it. I haven't replied to his criticisms yet and wish to do so now. One of the reasons is to avoid my position being misrepresented. By replying to Wiseman's criticisms, I also wish to clarify those issues in my standpoint that might have given rise to some of the misinterpretations. With the same purpose in mind, I will demarcate my concept of voluntary moral bioenhancement from related standpoints, in particular from Persson and Savulescu's notion of compulsory moral bioenhancement that, as I argued, diminishes our freedom (of the will). Furthermore, I will consider the possibility of adding another essential element to my position-one that I have not discussed in my earlier publications. It is designed to propose a novel explanation of why humans would be motivated to opt for voluntary moral bioenhancement if its outcome is not a lowering of the likelihood of "Ultimate Harm" (as defined by Persson and Savulescu) or a milder form of self-destruction of humanity. This explanation will be based on the conception that an increase in happiness, rather than Ultimate Harm prevention, might be the grounding rationale for moral bioenhancement. PMID- 28983862 TI - Proteomics in the Diagnosis of Inborn Encephalopathies of Unknown Origin: A Myth or Reality. AB - Synaptopathy underlies a great variety of neurological or neurodevelopmental disorders, including neurodegenerative diseases and the highly complex neuropsychiatric syndromes. Standard diagnostic assays in the majority of synaptopathies are insufficient to make an appropriate and fast diagnosis, which has spurred a search for more accurate diagnostic methods using recent technological advances. As synaptopathy phenotypes strictly depend on genetics and environmental factors, the best way to approach these diseases is the investigation of entire sets of protein characteristics. Thus, proteomics has emerged as a mainstay in the studies on synaptopathies, with mass spectrometry as a technology of choice. This review is an update on the proteomic methods and achievements in the understanding, diagnostics, and novel biomarkers of synaptopathies. The article also provides a critical point of view and future perspectives on the application of neuroproteomics in clinical practice. PMID- 28983863 TI - Therapeutic Efficacy of Mandibular Advancement Devices in Patients with Severe Sleep Apnea: A Preliminary Report. AB - Obstructive sleep apnea (OSA) is defined as episodes of upper airway obstructions during sleep. The method of choice in conservative treatment of OSA is the use of devices that produce positive airway pressure (CPAP). In patients with mild moderate form of OSA, intraoral mandibular advancement devices (MAD) are applied. The aim of the study was to evaluate the therapeutic efficacy of MAD in patients with severe OSA who were unable to use CPAP. In this preliminary study three patients from a group of 25 severe OSA sufferers who failed to use CPAP, were included. The three patients underwent a triple polysomnographic (PSG) investigation: on CPAP, before MAD treatment, and during MAD. The patients completed the Epworth Sleepiness Scale questionnaire twice. We found significant improvements of subjective symptoms and PSG-evaluated variables after application of MAD in all three patients in comparison with both baseline and CPAP-recorded data. We conclude that MAD can be an alternative treatment option for severe OSA patients who are non-compliant with CPAP therapy. PMID- 28983864 TI - Modeling Sexual Selection in Tungara Frog and Rationality of Mate Choice. AB - The males of the species of frogs Engystomops pustulosus produce simple and complex calls to lure females, as a way of intersexual selection. Complex calls lead males to a greater reproductive success than what simple calls do. However, the complex calls are also more attractive to their main predator, the bat Trachops cirrhosus. Therefore, as M. Ryan suggests in (The tungara frog: a study in sexual selection and communication. University of Chicago Press, Chicago, 1985), the complexity of the calls lets the frogs keep a trade-off between reproductive success and predation. In this paper, we verify this trade-off from the perspective of game theory. We first model the proportion of simple calls as a symmetric game of two strategies. We also model the effect of adding a third strategy, males that keep quiet and intercept females, which would play a role of intrasexual selection. Under the assumption that the decision of the males takes into account this trade-off between reproductive success and predation, our model reproduces the observed behavior reported in the literature with minimal assumption on the parameters. From the model with three strategies, we verify that the quiet strategy could only coexists with the simple and complex strategies if the rate at which quiet males intercept females is high, which explains the rarity of the quiet strategy. We conclude that the reproductive strategy of the male frog E. pustulosus is rational. PMID- 28983865 TI - Performance of automated multiplex PCR using sonication fluid for diagnosis of periprosthetic joint infection: a prospective cohort. AB - PURPOSE: Sonication of explanted prostheses improved the microbiological diagnosis of periprosthetic joint infections (PJI). We evaluated the performance of automated multiplex polymerase chain reaction (PCR) using sonication fluid for the microbiological diagnosis of PJI. METHODS: In a prospective cohort using uniform definition criteria for PJI, explanted joint prostheses were investigated by sonication and the resulting sonication fluid was analyzed by culture and multiplex PCR. McNemar's Chi-squared test was used to compare the performance of diagnostic tests. RESULTS: Among 111 patients, PJI was diagnosed in 78 (70%) and aseptic failure in 33 (30%). For the diagnosis of PJI, the sensitivity and specificity of periprosthetic tissue culture was 51 and 100%, of sonication fluid culture 58 and 100%, and of sonication fluid PCR 51 and 94%, respectively. Among 70 microorganisms, periprosthetic tissue culture grew 52 (74%), sonication fluid culture grew 50 (71%) and sonication fluid PCR detected 37 pathogens (53%). If only organisms are considered, for which primers are included in the test panel, PCR detected 37 of 58 pathogens (64%). The sonication fluid PCR missed 19 pathogens (predominantly oral streptococci and anaerobes), whereas 7 additional microorganisms were detected only by PCR (including Cutibacterium spp. and coagulase-negative staphylococci). CONCLUSIONS: The performance of multiplex PCR using sonication fluid is comparable to culture of periprosthetic tissue or sonication fluid. The advantages of PCR are short processing time (< 5 h) and fully automated procedure. However, culture technique is still needed due to the low sensitivity and the need of comprehensive susceptibility testing. Modification of primers or inclusion of additional ones may improve the performance of PCR, especially of low-virulent organisms. PMID- 28983866 TI - Running Performance, VO2max, and Running Economy: The Widespread Issue of Endogenous Selection Bias. AB - Studies in sport and exercise medicine routinely use samples of highly trained individuals in order to understand what characterizes elite endurance performance, such as running economy and maximal oxygen uptake VO2max. However, it is not well understood in the literature that using such samples most certainly leads to biased findings and accordingly potentially erroneous conclusions because of endogenous selection bias. In this paper, I review the current literature on running economy and VO2max, and discuss the literature in light of endogenous selection bias. I demonstrate that the results in a large part of the literature may be misleading, and provide some practical suggestions as to how future studies may alleviate endogenous selection bias. PMID- 28983867 TI - Mycobacterium abscessus Complex Infections in Children: A Review. AB - PURPOSE OF REVIEW: Infections in children with Mycobacterium abscessus complex represent a particular challenge for clinicians. Increasing incidence of these infections worldwide has necessitated focused attention to improve both diagnostic as well as treatment modalities. Published medical literature was reviewed, with emphasis on material published in the past 5 years. RECENT FINDINGS: Increasing availability of new diagnostic tools, such as matrix assisted laser desorption ionization-time of flight mass spectrometry and custom PCRs, has provided unique insights into the subspecies within the complex and improved diagnostic certainty. Microbiological review of all recent isolates at the University of Minnesota Medical Center was also conducted, with description of the antimicrobial sensitivity patterns encountered in our center, and compared with those published from other centers in the recent literature. A discussion of conventional antimicrobial treatment regimens, alongside detailed description of the relevant antimicrobials, is derived from recent publications. Antimicrobial therapy, combined with surgical intervention in some cases, remains the mainstay of pediatric care. Ongoing questions remain regarding the transmission mechanics, immunologic vulnerabilities exploited by these organisms in the host, and the optimal antimicrobial regimens necessary to enable a reliable cure. Updated treatment guidelines based on focused clinical studies in children and accounting especially for the immunocompromised children at greatest risk are very much needed. PMID- 28983868 TI - The Race Structure of the Rice Blast Pathogen Across Southern and Northeastern China. AB - BACKGROUND: Rice blast, caused by the ascomycete Magnaporthe oryzae (Mo), imposes a major constraint on rice productivity. Managing the disease through the deployment of host resistance requires a close understanding of race structure of the pathogen population. RESULTS: The host/pathogen interaction between isolates sampled from four Mo populations collected across the rice-producing regions of China was tested using two established panels of differential cultivars. The clearest picture was obtained from the Chinese cultivar panel, for which the frequency of the various races, the race diversity index, the specific race isolate frequency, and the frequency of the three predominant races gave a consistent result, from which it was concluded that the pathogen population present in the southern production region was more diverse than that in the northeastern region. The four blast resistance genes Pi1, Pik, Pik-m, and Piz all still remain effective in the southern China rice production area, as does Pi1 in the northeastern region. The effectiveness of Pita, Pik-p, Piz, and Pib is restricted to single provinces. The distinctive resistance profile shown by the Chinese differential cultivar set implied the presence of at least five as yet unidentified blast resistance genes. CONCLUSIONS: The Chinese differential cultivar set proved to be more informative than the Japanese one for characterizing the race structure of the rice blast pathogen in China. A number of well characterized host resistance genes, in addition to some as yet uncharacterized ones, remain effective across the major rice production regions in China. PMID- 28983869 TI - Bipolar Effects in Photovoltage of Metamorphic InAs/InGaAs/GaAs Quantum Dot Heterostructures: Characterization and Design Solutions for Light-Sensitive Devices. AB - The bipolar effect of GaAs substrate and nearby layers on photovoltage of vertical metamorphic InAs/InGaAs in comparison with pseudomorphic (conventional) InAs/GaAs quantum dot (QD) structures were studied. Both metamorphic and pseudomorphic structures were grown by molecular beam epitaxy, using bottom contacts at either the grown n +-buffers or the GaAs substrate. The features related to QDs, wetting layers, and buffers have been identified in the photoelectric spectra of both the buffer-contacted structures, whereas the spectra of substrate-contacted samples showed the additional onset attributed to EL2 defect centers. The substrate-contacted samples demonstrated bipolar photovoltage; this was suggested to take place as a result of the competition between components related to QDs and their cladding layers with the substrate related defects and deepest grown layer. No direct substrate effects were found in the spectra of the buffer-contacted structures. However, a notable negative influence of the n +-GaAs buffer layer on the photovoltage and photoconductivity signal was observed in the InAs/InGaAs structure. Analyzing the obtained results and the performed calculations, we have been able to provide insights on the design of metamorphic QD structures, which can be useful for the development of novel efficient photonic devices. PMID- 28983870 TI - Extraction and representation of common feature from uncertain facial expressions with cloud model. AB - Human facial expressions are key ingredient to convert an individual's innate emotion in communication. However, the variation of facial expressions affects the reliable identification of human emotions. In this paper, we present a cloud model to extract facial features for representing human emotion. First, the uncertainties in facial expression are analyzed in the context of cloud model. The feature extraction and representation algorithm is established under cloud generators. With forward cloud generator, facial expression images can be re generated as many as we like for visually representing the extracted three features, and each feature shows different roles. The effectiveness of the computing model is tested on Japanese Female Facial Expression database. Three common features are extracted from seven facial expression images. Finally, the paper is concluded and remarked. PMID- 28983871 TI - Human amylin induces CD4+Foxp3+ regulatory T cells in the protection from autoimmune diabetes. AB - Autoimmune diabetes is a disorder of immune homeostasis that leads to targeted insulin-secreting islet beta cell destruction characterized by insulitis. Human amylin (hA) is an important neuroendocrine hormone co-secreted with insulin by pancreatic beta cells. Here, we report hA immune-modulatory action through inducing regulatory T cells. We ex vivo-treated human peripheral blood mononuclear cells (hPBMCs) with hA for 24 h and counted CD4+Foxp3+ regulatory T cells (Treg) using flow cytometry. Diabetic status was monitored and splenic Treg were measured in non-obese diabetic (NOD) male mice. NOD mice were intraperitoneally injected once daily with hA (n = 25) or solvent for control (n = 25) for 7 months continuously. Spleen tissues were collected at the end of intervention and processed for flow cytometry and Western blot. We found a 2.9 fold (p < 0.05) increase of CD4+Foxp3+ Treg in hPBMCs treated with 10 nmol/L hA compared with negative control. Incidence of diabetes in hA-treated NOD mice decreased 44% (p = 0.045) in the 6th month and 57% (p = 0.0002) in the 7th month. Meanwhile, the hA treatment induced a 1.5-fold increase of CD4+Foxp3+ Treg from mouse splenocytes (p = 0.0013). Expression of transforming growth factor-beta (TGF-beta) and toll-like receptor-4 (TLR-4) were upregulated in hA-treated mice. Human amylin might protect against autoimmune diabetes via the induction of CD4+Foxp3+ Treg, which suggests a novel approach to improve autoimmune conditions. PMID- 28983872 TI - Pearls and pitfalls of optical coherence tomography angiography in the multimodal evaluation of uveitis. AB - BACKGROUND: Optical coherence tomography angiography (OCTA) employs a novel imaging algorithm that detects the amplitude or phase decorrelation of blood cell movement. It thus provides a flow map with depth-resolved visualization of the various vascular layers in the posterior pole of the eye including the retina capillary plexus and the choroid. In the past 3 years, the number of research papers on the subject of OCTA in retinal diseases has grown exponentially including important applications in the field of uveitis. While the study of OCTA in uveitic diseases has gained remarkable relevance worldwide, interpretation can be challenging, and many limitations exist in optimally using this advanced system in uveitic eyes. The aim of this review is to describe the many significant applications of OCTA in uveitis disorders and to outline the various limitations that can confound interpretation and support uveitis specialists in the integration of OCTA in the multimodal imaging approach to inflammatory diseases. MAIN BODY: Unlike conventional angiography that can dynamically detect inflammation and leakage of dye from retinal vessels, OCTA provides other important biomarkers of inflammation. Detailed microvascular reconstruction of normal and abnormal blood vessels and quantitative evaluation are advantages of OCTA analysis. OCTA can therefore non-invasively detect choroidal neovascularization that may complicate inflammatory disorders, and with remarkable depth-resolved capability, OCTA can identify and quantitate flow loss as a manifestation of ischemia and/or inflammation. The areas of flow deficit on OCTA at the level of the inner choroid often co-localize with hypofluorescent lesions with indocyanine green angiography. These regions of presumed choriocapillaris ischemia may occur in placoid disorders. Space-occupying granulomas may occur in disorders such as sarcoid and may or may not co-localize with choriocapillaris ischemia on ICG angiography. Blocking or shadowing artifacts should be excluded when evaluating inner choroidal abnormalities with OCT angiography. Fundus autofluorescence may assess the metabolic function of the retinal pigment epithelium (RPE) and the viability of the overlying photoreceptors and thus the activity of inflammation associated with uveitic lesions. The photoreceptors are physiologically maintained by the diffusion of oxygen from the choriocapillaris below and, to a lesser extent, from the deep retinal capillary plexus above. The depth-resolved capability of OCTA may therefore provide additional significant microvascular information about these vascular layers that may be driving the development of hyper-autofluorescent RPE inflammation and photoreceptor loss. CONCLUSIONS: The implementation of OCTA in the evaluation and management of uveitis disorders is being spurred by our greater knowledge and understanding of its application. In order to take full advantage of this exciting new imaging modality, however, uveitis specialists must understand the limitations of interpretation and potential artifact-related pitfalls in assessment and should continue to support evaluation with multimodal imaging to best optimize diagnoses and treatment of inflammatory diseases. PMID- 28983873 TI - Updates in Lupus Genetics. AB - PURPOSE OF REVIEW: Our understanding on genetic basis of SLE has been advanced through genome-wide association studies. We review recent progress in lupus genetics with a focus on SLE-associated loci that have been functionally characterized, and discuss the potential for clinical translation of genetics data. RECENT FINDINGS: Over 100 loci have been confirmed to show robust association with SLE and many share with other immune-mediated diseases. Although causative variants captured at these established loci are limited, they guide biological studies of gene targets for functional characterization which highlight the importance of aberrant recognition of self-nucleic acid, type I interferon overproduction, and defective immune cell signaling underlying the pathogenesis of SLE. Increasing examples illustrate a predictive value of genetic findings in susceptibility/prognosis prediction, clinical classification, and pharmacological implication. Genetic findings provide a foundation for better understanding of disease pathogenic mechanisms and opportunities for target selection in lupus drug development. PMID- 28983874 TI - Towards Personal Exposures: How Technology Is Changing Air Pollution and Health Research. AB - PURPOSE OF REVIEW: We present a review of emerging technologies and how these can transform personal air pollution exposure assessment and subsequent health research. RECENT FINDINGS: Estimating personal air pollution exposures is currently split broadly into methods for modeling exposures for large populations versus measuring exposures for small populations. Air pollution sensors, smartphones, and air pollution models capitalizing on big/new data sources offer tremendous opportunity for unifying these approaches and improving long-term personal exposure prediction at scales needed for population-based research. A multi-disciplinary approach is needed to combine these technologies to not only estimate personal exposures for epidemiological research but also determine drivers of these exposures and new prevention opportunities. While available technologies can revolutionize air pollution exposure research, ethical, privacy, logistical, and data science challenges must be met before widespread implementations occur. Available technologies and related advances in data science can improve long-term personal air pollution exposure estimates at scales needed for population-based research. This will advance our ability to evaluate the impacts of air pollution on human health and develop effective prevention strategies. PMID- 28983875 TI - Erratum to: volume 73, issue 3 of Journal of Physiology and Biochemistry. AB - Volume 73 issue 3 was published with an incorrect cover date. Correct is August 2017. The Publisher apologizes for this mistake and all related inconveniences caused by this. PMID- 28983876 TI - Novel Missense LCAT Gene Mutation Associated with an Atypical Phenotype of Familial LCAT Deficiency in Two Portuguese Brothers. AB - Familial lecithin-cholesterol acyltransferase deficiency (FLD) is a rare recessive disorder of cholesterol metabolism, caused by loss-of-function mutations in the human LCAT gene, leading to alterations in the lipid/lipoprotein profile, with extremely low HDL levels.The classical FLD phenotype is characterized by diffuse corneal opacification, haemolytic anaemia and proteinuric chronic kidney disease (CKD); an incomplete form, only affecting the corneas, has been reported in a few families worldwide.We describe an intermediate phenotype of LCAT deficiency, with CKD preceding the development of corneal clouding, in two Portuguese brothers apparently homozygous for a novel missense LCAT gene mutation. The atypical phenotype, the diagnosis of membranous nephropathy in the proband's native kidney biopsy, the late-onset and delayed recognition of the corneal opacification, the co-segregation with Gilbert syndrome and the late recurrence of the primary disease in kidney allograft all contributed to obscure the diagnosis of an LCAT deficiency syndrome for many years.A major teaching point is that on standard light microscopy examination the kidney biopsies of patients with LCAT deficiency with residual enzyme activity may not show significant vacuolization and may be misdiagnosed as membranous nephropathy. The cases of these two patients also illustrate the importance of performing detailed physical examination in young adults presenting with proteinuric CKD, as the most important clue to the diagnosis of FLD is in the eyes. PMID- 28983877 TI - A systematic review of the use of local analgesia in medically compromised children and adolescents. AB - AIM: To determine if the use of routine techniques and agents for topical and injectable dental local analgesia (LA) are safe for use in medically compromised children and adolescents. METHOD: Medline, Embase and Cochrane Oral Health Group's trials register, were searched electronically, supplemented by hand searching of relevant journals. SELECTION CRITERIA: RCTs, cohort studies, case control studies, observational studies, case series, case reports, evidence based guidelines reporting on children and adolescents aged 18 years or younger with one/more pre-designated medical condition, being administered topical and/or injectable local analgesic for dental procedures using standard techniques of delivery. Outcomes were presence of adverse events which were attributable directly or indirectly to the underlying medical condition. RESULTS: N = 71 studies were retrieved but only three observational studies, one case series, two case reports and four evidence based guidelines met the criteria for inclusion. A disparate set of medical conditions were reported upon and sparse guidance given in these areas. Thirty-nine review articles and consensus documents provided little or no clinical data to support their recommendations. CONCLUSIONS: There are insufficient high quality data reporting on the use of topical and local analgesia to medically compromised children and adolescents. Apart from a known allergy to local analgesia or one of the agents, there appears to be very few absolute or relative contra-indications to the use of local analgesia in children and adolescents based on medical history. There is an urgent need for high quality studies wherever possible and appropriate, in order to improve and inform the evidence-base in this cohort. PMID- 28983878 TI - Erratum to: Ultrapure dialysis water obtained with additional ultrafilter may reduce inflammation in patients on hemodialysis. AB - In original publication, the Table 4 was incorrect. The correct Table has been given below. PMID- 28983879 TI - Capturing forest dependency in the central Himalayan region: Variations between Oak (Quercus spp.) and Pine (Pinus spp.) dominated forest landscapes. AB - Our study explores the nexus between forests and local communities through participatory assessments and household surveys in the central Himalayan region. Forest dependency was compared among villages surrounded by oak-dominated forests (n = 8) and pine-dominated forests (n = 9). Both quantitative and qualitative analyses indicate variations in the degree of dependency based on proximity to nearest forest type. Households near oak-dominated forests were more dependent on forests (83.8%) compared to households near pine-dominated forests (69.1%). Forest dependency is mainly subsistence-oriented for meeting basic household requirements. Livestock population, cultivated land per household, and non-usage of alternative fuels are the major explanatory drivers of forest dependency. Our findings can help decision and policy makers to establish nested governance mechanisms encouraging prioritized site-specific conservation options among forest-adjacent households. Additionally, income diversification with respect to alternate livelihood sources, institutional reforms, and infrastructure facilities can reduce forest dependency, thereby, allowing sustainable forest management. PMID- 28983880 TI - Cannabis and Cannabinoids for Chronic Pain. AB - PURPOSE OF REVIEW: The purpose of this study was to provide the most up-to-date scientific evidence of the potential analgesic effects, or lack thereof, of the marijuana plant (cannabis) or cannabinoids, and of safety or tolerability of their long-term use. RECENT FINDINGS: We found that inhaled (smoked or vaporized) cannabis is consistently effective in reducing chronic non-cancer pain. Oral cannabinoids seem to improve some aspects of chronic pain (sleep and general quality of life), or cancer chronic pain, but they do not seem effective in acute postoperative pain, abdominal chronic pain, or rheumatoid pain. The available literature shows that inhaled cannabis seems to be more tolerable and predictable than oral cannabinoids. Cannabis or cannabinoids are not universally effective for pain. Continued research on cannabis constituents and improving bioavailability for oral cannabinoids is needed. Other aspects of pain management in patients using cannabis require further open discussion: concomitant opioid use, medical vs. recreational cannabis, abuse potential, etc. PMID- 28983882 TI - Assessing Doping Prevalence is Possible. So What Are We Waiting For? PMID- 28983881 TI - Alzheimer's disease and driving: review of the literature and consensus guideline from Belgian dementia experts and the Belgian road safety institute endorsed by the Belgian Medical Association. AB - Alzheimer's disease (AD) is a highly prevalent condition and its prevalence is expected to further increase due to the aging of the general population. It is obvious that the diagnosis of AD has implications for driving. Finally, driving discussions are also emotionally charged because driving is associated with independence and personal identity. However, it is not clear how to implement this in clinical practice and the Belgian law on driving is rather vague in its referral to neurodegenerative brain diseases in general nor does it provide clear cut instructions for dementia or AD compared to for example driving for patients with epilepsy and as such does not prove to be very helpful. The present article reviews what is known from both literature and existing guidelines and proposes a consensus recommendation tailored to the Belgian situation agreed by both AD experts and the Belgian Road Safety Institute endorsed by the Belgian Medical Association. It is concluded that the decision about driving fitness should be considered as a dynamic process where the driving fitness is assessed and discussed early after diagnosis and closely monitored by the treating physician. The diagnosis of AD on itself definitely does not imply the immediate and full revocation of a driving license nor does it implicate a necessary referral for a formal on-road driving assessment. There is no evidence to recommend a reduced exposure or a mandatory co-pilot. A MMSE-based framework to trichotomise AD patients as safe, indeterminate or unsafe is presented. The final decision on driving fitness can only be made after careful history taking and clinical examination, neuropsychological, functional and behavioral evaluation and, only for selected cases, a formal assessment of driving performance. PMID- 28983883 TI - Correction to: Impact of a mixed educational and semi-restrictive antimicrobial stewardship project in a large teaching hospital in Northern Italy. AB - A technical error led to incorrect rendering of the author group in this article. The correct authorship is as follows: Daniele Roberto Giacobbe1, Valerio Del Bono1, Malgorzata Mikulska1, Giulia Gustinetti1, Anna Marchese2, Federica Mina3, Alessio Signori4, Andrea Orsi5, Fulvio Rudello6, Cristiano Alicino5, Beatrice Bonalumi3, Alessandra Morando7, Giancarlo Icardi5, Sabrina Beltramini3, Claudio Viscoli1; On behalf of the San Martino Antimicrobial Stewardship Group. PMID- 28983884 TI - Erratum to: Sub-chronic exposure to low concentration of dibutyl phthalate affects anthropometric parameters and markers of obesity in rats. AB - The correct name of the 1st and corresponding Author is Khalid Abdul Majeed. PMID- 28983885 TI - Shielding of medical imaging X-ray facilities: a simple and practical method. AB - The most widely accepted method for shielding design of X-ray facilities is that contained in the National Council on Radiation Protection and Measurements Report 147 whereby the computation of the barrier thickness for primary, secondary and leakage radiations is based on the knowledge of the distances from the radiation sources, the assumptions of the clinical workload, and usage and occupancy of adjacent areas. The shielding methodology used in this report is complex. With this methodology, the shielding designers need to make assumptions regarding the use of the X-ray room and the adjoining areas. Different shielding designers may make different assumptions resulting in different shielding requirements for a particular X-ray room. A more simple and practical method is to base the shielding design on the shielding principle used to shield X-ray tube housing to limit the leakage radiation from the X-ray tube. In this case, the shielding requirements of the X-ray room would depend only on the maximum radiation output of the X-ray equipment regardless of workload, usage or occupancy of the adjacent areas of the room. This shielding methodology, which has been used in South Australia since 1985, has proven to be practical and, to my knowledge, has not led to excess shielding of X-ray installations. PMID- 28983886 TI - Opioid receptor antagonists in the treatment of pathological gambling. PMID- 28983887 TI - Effect of tranexamic acid use on blood loss and thromboembolic risk in hip fracture surgery: systematic review and meta-analysis. AB - INTRODUCTION: Intravenous tranexamic acid (IV TXA) is a recognised pharmaceutical intervention utilised to minimise blood loss and allogenic blood transfusion. However, the use of IV TXA in hip fracture surgery remains inconclusive. We conducted a meta-analysis to investigate the role of TXA in operative hip fracture management on operative and total blood loss, allogenic blood transfusion requirements and impact on venous thromboembolic (VTE) event incidence. METHODS: A systematic computerised literature search of PubMed, Medline, Embase, Ovid, The Cochrane Controlled Trials Register, Trip and Google was conducted. We reviewed the efficacy of IV TXA on perioperative blood loss, total blood loss, pre- and postoperative haemoglobin differences, duration of surgery, allogenic blood transfusion requirements and VTE events. RESULTS: 8 studies were eligible including 6 randomised control trials and 2 cohort studies. Patients receiving IV TXA had reduced mean total blood loss of 442.9 mls (95% CI, 426.5-459.3; p<0.00001), reduced operative blood loss of 88.5 mls (95% CI, 59.9 117.2; p<0.00001), a decrease in the need for allogenic blood transfusion (OR 0.37; 95% CI, 0.26-0.53; p<0.00001) and a reduction in pre- and postoperative haemoglobin difference (p = 0.013.) There was no significant increase in VTE risk (OR 1.59; 95% CI 0.67-3.75; p>0.29) or significant difference on duration of surgery seen with IV TXA usage (p>0.06). CONCLUSIONS: Our review demonstrated the efficacy of IV TXA in minimising perioperative, reducing total blood loss and lowering the necessity for allogenic blood transfusions with no significant increased risk in VTE events. PMID- 28983888 TI - Indirect versus direct hip MR arthrography: an alternative imaging approach to improve patient comfort. PMID- 28983889 TI - Metallisation of Biolox Delta(r) ceramic head: What's wrong? AB - INTRODUCTION: Since the recent failure of certain coating models, hybrid implants (coated acetabular inserts with conventional stems) and stems with modular necks, there has been growing interest in the consequences of the generation and release of metal particles at the prosthetic interfaces. The use of ceramic heads has recently been described as an option for reducing the production of metal ions and their consequences. CASE REPORT: The present case report describes the first complete metallisation of a ceramic head secondary to an excessive release of metal ions at the head-neck junction. CONCLUSIONS: We believe this to have occurred due to the use of 12/14 cones of different manufacturers. PMID- 28983890 TI - Skin closure following fractured neck of femur surgery: a survey of orthopaedic surgeons' practices. AB - INTRODUCTION: Surgical intervention for patients presenting with a fractured neck of femur is common, however the best method of skin closure remains unclear. It has been suggested that the use of metallic skin clips in the closure of hip wounds may increase the rate of surgical site infections, however there are few high quality studies evaluating this. METHODS: We designed a survey to assess surgeons preferred skin closure method and their reasons for choosing it. This was sent to 545 consultant orthopaedic surgeons. RESULTS: The positive response rate to our survey was 68% (n = 370). The survey showed that 44% of surgeons used metallic skin clips, and this was the most common method of closure reported. Hip surgeons were less likely to use metallic skin clips when compared to surgeons with other principal subspecialty practices. Surgeons using clips were most likely to state the rationale for use as convenience, whereas those using non clip skin closure methods were more likely to cite reduced rates of wound inflammation, discharge, and infection as the rationale for use. Only a small proportion of surgeons indicate that their decisions were evidence based. CONCLUSIONS: Skin closure following surgery for fractured neck of femur is not consistent amongst surgeons and is not driven by evidence. Greater levels of evidence in this field are required to improve outcomes in this patient group. PMID- 28983891 TI - Infection and failure rates following total hip arthroplasty for septic arthritis: a case-controlled study. AB - INTRODUCTION: Total hip arthroplasty (THA) is performed as a 2-stage or single stage procedure in patients with a history of septic arthritis of the native hip joint. The decision is based on whether the infection is active or quiescent in the joint. The aim of this study was to compare the outcomes of total hip arthroplasty for septic arthritis of the native hip to a control series of patients treated for primary osteoarthritis of the hip with standard THA. METHODS: Between March 2000 and March 2013, 18 cases of septic arthritis of the hip treated with THA were retrospectively identified. During the same time period, 18 control cases of THA for degenerative osteoarthritis were identified. Cases and controls were comparable in age, gender, body mass index, type of anaesthesia and American Society of Anesthesiologists score. RESULTS: 11 and 7 cases received 2-stage and single stage total hip arthroplasty respectively for septic arthritis. There was a mean interval of 4 months between 1st and 2nd-stage operations. Cases and controls were followed up for a mean of 70 and 72 months respectively. There was no reinfection or implant failure in the cases, and comparable functional outcomes between cases and controls. CONCLUSIONS: Two-stage and single-stage THA for active and quiescent native hip infection respectively, achieved similar outcomes to THA for primary osteoarthritis in controls. PMID- 28983892 TI - Tubeless versus standard percutaneous nephrolithotomy in pediatric patients: a systematic review and meta-analysis. AB - BACKGROUND: This systematic review and meta-analysis was designed to evaluate the post-operative outcomes between tubeless and standard percutaneous nephrolithotomy (PCNL) among children. METHODS: Literature searches were performed following the Cochrane guidelines. We conducted a systematic review and meta-analysis that included three trials investigating the outcomes including the length of hospital stay, operation time, hemoglobin decrease, blood transfusion rate, perirenal fluid presence, post-operative fever, stone clearance rate, and the need for a second operation. RESULTS: The patients who underwent tubeless PCNL had shorter length of hospitalization compared to standard PCNLs (mean difference -1.57, 95% confidence interval -3.2 to 0.07, p = 0.06). No significant decrease was detected in hemoglobin after tubeless PCNL compared to standard PCNL (mean difference 0.05, 95% confidence interval -0.03 to 0.13, p = 0.21). There were no significant differences in operation time (p = 0.7), perirenal fluid presence (p = 0.15), post-operative fever (p = 0.72), stone clearance (p = 0.68), and the need for a second operation (p = 0.90). CONCLUSIONS: This study showed no significant difference between tubeless and standard PCNLs in children. However, due to the lack of data, the results should be mentioned prudently. Future randomized trials with more sample sizes and longer follow-ups are warranted. PMID- 28983893 TI - Development of late enophthalmos in pure blowout fractures: methodologic issues in prediction studies. PMID- 28983894 TI - Consecutive case series of 244 age-related macular degeneration patients undergoing implantation with an extended macular vision IOL. AB - PURPOSE: To determine safety and visual outcomes in eyes with age-related macular degeneration (AMD) implanted with a novel intraocular lens (IOL) that delivers an optimized retinal image to all macular areas within 10 degrees of retinal eccentricity. METHODS: This was a consecutive case series of 244 eyes with dry/stable wet AMD and logMAR visual acuity >=0.3 implanted with iolAMD Eyemax monoTM (London Eye Hospital Pharma), a single-piece, injectable, hydrophobic acrylic IOL sited in the capsular bag. Primary outcome was safety. Secondary outcomes were changes in corrected distance visual acuity (CDVA) and corrected near visual acuity (CNVA) (logMAR). RESULTS: Mean age at surgery was 80 years. Mean duration of follow-up was 3 months (range 1-16 months). No eyes had worsening of CDVA. Frequency of perioperative complications was equivalent to standard IOL implantation. Postoperative refractive outcomes were within +/-1 D of the target refraction in 88% of cases. Mean preoperative CDVA improved from 1.06 to 0.71 postoperatively (mean of differences -0.35; 95% confidence interval [CI] -0.3886 to -0.3223; p<0.0001), equating to an approximate Early Treatment Diabetic Retinopathy Study gain of 18 letters. Mean preoperative CNVA (N-point; logMAR conversion) improved from 1.36 to 0.88 postoperatively (mean of differences -0.48; 95% CI -0.53 to -0.44; p<0.0001). CONCLUSIONS: This novel IOL appears safe in the short to medium term. Improvements in postoperative CDVA and CNVA exceed those observed with standard implants. PMID- 28983895 TI - LncRNA GHET1 promotes esophageal squamous cell carcinoma cells proliferation and invasion via induction of EMT. AB - BACKGROUND: Recent studies have shown that long noncoding RNA (lncRNA) gastric carcinoma highly expressed transcript 1 (GHET1) was involved in the progression of tumors. However, the role of GHET1 in esophageal squamous cell carcinoma (ESCC) remains unclear. METHODS: The expression of lncRNA GHET1 was examined in 55 paired ESCC tissues and adjacent nontumor tissues. Molecular and cellular techniques were used to explore the role of GHET1 on ESCC cells. RESULTS: Our data showed that GHET1 expression was significantly increased in ESCC tissues and cell lines. High GHET1 expression in ESCC tissues was significantly associated with poor differentiation, advanced tumor nodes metastasis stage, and lymph node metastasis. GHET1 showed high sensitivity and specificity for diagnosing ESCC. Our data from in vitro assays showed that GHET1 inhibition suppressed ESCC cells proliferation, migration, and invasion, and induced cells apoptosis. Furthermore, western blot showed that GHET1 inhibition significantly decreased the expression of vimentin and N-cadherin while it increased the expression of E-cadherin. CONCLUSIONS: Our study indicates that GHET1 acts as an oncogene in ESCC and may represent a novel therapeutic target for the treatment of ESCC patients. PMID- 28983896 TI - Authors' reply to Comments on: Over-catheter tract suture to prevent bleeding and air embolism after tunneled catheter removal. PMID- 28983898 TI - Comments on: Over-catheter tract suture to prevent bleeding and air embolism after tunneled catheter removal. PMID- 28983897 TI - Left axillary to right atrium anterior chest wall graft using bovine carotid artery conduit. AB - INTRODUCTION: Central venous occlusive (CVO) disease involving the superior vena cava (SVC) and inferior vena cava (IVC) can occur frequently in patients with end stage renal disease (ESRD) on chronic dialysis. Dialysis access is essential for the survival of these patients. CASE DESCRIPTION: We report a case of a chest wall graft creation using bovine carotid artery conduit in a patient who was experiencing life-threatening loss of dialysis access secondary to her SVC and IVC occlusion along with a hypercoagulable state. We did a subcutaneous anterior chest wall graft from the left axillary artery to the right atrium (RA) using a mini thoracotomy incision. CONCLUSIONS: ESRD patients with CVO pose a unique challenge. We believe our approach can provide an excellent option for dialysis access in patients with exhausted conventional access options. PMID- 28983899 TI - Understanding patient preferences for femoral central venous catheterization among patients with sickle cell disease. PMID- 28983900 TI - Predicting tissue plasminogen activator use and success in in-center hemodialysis patients. AB - INTRODUCTION: Hemodialysis catheter malfunction is problematic. We aimed to determine clinical, catheter, and hemodialysis variables that predict: (i) catheter malfunction requiring recombinant tissue-plasminogen activator (TPA) treatment and (ii) the success of TPA administration. METHODS: Clinical, catheter, and hemodialysis variables were collected from a cohort of 559 catheters (141,526 catheter days) in 175 hemodialysis patients (2008-2011). Time to, and predictors of, catheter malfunction were determined for all catheters and primary catheters only, analyzed by Cox-proportional hazard model, multi-variable logistic regression model, and mixed-effect logistic regression models. Success of TPA use was determined immediately, next day, and two weeks after use. RESULTS: Shorter time to first TPA administration in all patient's catheters was associated with increased body mass index (hazard ratio [HR] = 1.06, 1.01-1.11, p = 0.03) and being of black race (HR = 3.05, 1.65-5.67, p<0.01). Primary TPA administration success at two weeks among primary catheters was associated with increased mean peak venous pressure before TPA administration (odds ratio [OR] = 1.03, 1.01-1.06, p<0.01) and decreased mean of the lowest systolic blood pressure measure for the three dialysis sessions prior to TPA administration (OR = 0.95, 0.91-0.99, p = 0.02). TPA administration success at two weeks among all catheters was associated with decreasing body mass index (OR = 0.84, CI 0.73-0.96, p = 0.01) and having diabetes (OR = 7.19, 1.40-36.81, p = 0.02). CONCLUSIONS: Both patient and dialysis predictors of TPA use and success were identified in this study, which may be useful for fine-tuning catheter management protocols to target hemodialysis patients at high risk of catheter malfunction. PMID- 28983901 TI - A novel insight into the role of entry tears in type B aortic dissection: pressure measurements in an in vitro model. AB - INTRODUCTION: Predicting aortic growth in acute type B dissection is fundamental in planning interventions. Several factors are considered to be growth predictors in the literature and, among them, size and location of entry tears have been recognized to particularly influence the false lumen pressure. In this study, we develop an in vitro setting to analyze the actual impact of size and location of the entry tears on false lumen pressure, in the absence of other confounding factors such as the deformability of the aortic wall. METHODS: We formalize some indexes that synthetically describe the false lumen pressure with respect to the true lumen pressure. Then, we experimentally derive their values in several configurations of the in vitro setting, and we look for trends in the indexes with respect to the size and location of entry tears. RESULTS: Results show that the tears have a relevant impact on the false lumen pressure, but that their size and location alone are not enough to explain the phenomena observed in vivo. CONCLUSIONS: To predict the behavior of acute type B dissection, we therefore recommend not limiting to size and location, as many effects may derive from the interactions between these parameters and other patient characteristics. PMID- 28983902 TI - Intractable seizures after a lengthy remission in childhood-onset epilepsy. AB - OBJECTIVES: To establish the risk of subsequent intractable epilepsy after >=2, >=5, and >=10 years of remission in childhood-onset epilepsy. METHODS: From the Nova Scotia childhood-onset epilepsy population-based cohort patients with all types of epilepsy were selected with >=20 years follow-up from seizure onset (incidence cases). Children with childhood absence epilepsy were excluded. The rate of subsequent intractable epilepsy was then studied for patients with >=5 years remission on or off AED treatment and compared with the rate for those with >=2 and >=10 years of remission. RESULTS: Three hundred eighty-eight eligible patients had >=20 years follow-up (average 27.7 +/- (standard deviation) 4 years) until they were an average of 34 +/- 6.5 years of age. Overall, 297 (77%) had a period of >=5 years of seizure freedom (average 21.2 +/- 8 years), with 90% of these remissions continuing to the end of follow-up. Seizures recurred in 31 (10%) and were intractable in 7 (2%). For the 332 with a remission of >=2 years seizure-free, 6.9% subsequently developed intractable epilepsy (p = 0.001). For the 260 with >=10 years remission, 0.78% subsequently developed intractable epilepsy (p = 0.25 compared with >=5 years remission). SIGNIFICANCE: Even after >=5 or >=10 years of seizure freedom, childhood-onset epilepsy may reappear and be intractable. The risk is fortunately small, but for most patients it is not possible to guarantee a permanent remission. PMID- 28983903 TI - Dynamic ultrasound-guided short-axis needle tip navigation technique vs. landmark technique for difficult saphenous vein access in children: a randomised study. AB - Dynamic ultrasound-guided short-axis needle tip navigation is a novel technique for vascular access. After venipuncture, the needle and catheter are further advanced within the vessel lumen under real-time ultrasound guidance with constant visualisation of the needle tip in the short-axis view. This can minimise the risk of transfixing the cannulated vessel. We compared two techniques for non-visible saphenous vein cannulation under general anaesthesia in children weighing >= 3 kg and less than four years of age: dynamic ultrasound guided short-axis needle tip navigation technique (ultrasound group) vs. landmark technique. Venous cannulation was performed by three experienced anaesthetists. The primary outcome measure was first-attempt success rate. Success rate within 10 min was a secondary outcome. A total of 102 patients were randomly allocated to either the ultrasound group or the landmark group. First-attempt success rate was 90% in the ultrasound group compared with 51% in the landmark group, p<0.001, difference 39%, 95% confidence interval (CI) of the difference 23-55%. Success rate within 10 min was 92% in the ultrasound group compared with 63% in the landmark group, p = 0.001, difference 29%, 95%CI of the difference 14-45%. We conclude that, when performed by experienced anaesthetists, the dynamic ultrasound-guided short-axis needle tip navigation technique improved non-visible saphenous vein cannulation in children compared with the landmark technique. PMID- 28983904 TI - Pre-operative variables including fitness associated with complications after oesophagectomy. AB - Oesophagectomy is a technically-demanding operation associated with a high level of morbidity. We analysed the association of pre-operative variables, including those from cardiopulmonary exercise testing, with complications (logistic regression) and survival and length of stay (Cox regression) after scheduled transthoracic oesophagectomy in 273 adults, in isolation and on multivariate testing (maximum Akaike information criterion). On multivariate analysis, any postoperative complication was associated with ventilatory equivalents for carbon dioxide, odds ratio (95%CI) 1.088 (1.02-1.17), p = 0.018. Cardiorespiratory complications were associated with FEV1 and pre-operative background survival (in an analogous group without cancer), odds ratios (95%CI) 0.55 (0.37-0.80), p = 0.002 and 0.89 (0.82-0.96), p = 0.004, respectively. Survival was associated with the ratio of expected-to-observed ventilatory equivalents for carbon dioxide and predicted postoperative survival, hazard ratios (95%CI) 0.17 (0.03-0.91), p = 0.039 and 0.96 (0.90-1.01), p = 0.076. Length of hospital stay was associated with FVC, hazard ratio (95%CI) 1.38 (1.17-1.63), p < 0.0001. PMID- 28983905 TI - Right heart masses demonstrated by echocardiography in a patient with amniotic fluid embolism during labour. PMID- 28983906 TI - A newborn infant chimpanzee snatched and cannibalized immediately after birth: Implications for "maternity leave" in wild chimpanzee. AB - OBJECTIVES: This study reports on the first observed case of a wild chimpanzee infant being snatched immediately after delivery and consequently cannibalized by an adult male in the Mahale Mountains, Tanzania. We demonstrate "maternity leave" from long-term data from the Mahale M group and suggest that it functions as a possible counterstrategy of mother chimpanzees against the risk of infanticide soon after delivery. MATERIALS AND METHODS: The subjects of this study were the M group chimpanzees at Mahale Mountains, Tanzania. The case of cannibalism was observed on December 2, 2014. We used the long-term daily attendance record of the M group chimpanzees between 1990 and 2010 to calculate the lengths of "maternity leave," a perinatal period during which a mother chimpanzee tends to hide herself and gives birth alone. RESULTS: We observed a very rare case of delivery in a wild chimpanzee group. A female chimpanzee gave birth in front of other members, and an adult male snatched and cannibalized the newborn infant immediately after birth. Using the long-term data, we demonstrate that the length of "maternity leave" is longer than that of nonmaternity leave among adult and adolescent female chimpanzees. DISCUSSION: We argue that this cannibalism event immediately after birth occurred due to the complete lack of "maternity leave" of the mother chimpanzee of the victim, who might lack enough experience of delivery. We suggest that "maternity leave" taken by expecting mothers may function as a possible counterstrategy against infanticide soon after delivery. PMID- 28983907 TI - Rapid vasodilation to raloxifene: role of oestrogen receptors and off-target effects. PMID- 28983908 TI - Interventions for managing medication-related osteonecrosis of the jaw. AB - BACKGROUND: Medication-related osteonecrosis of the jaw (MRONJ) is a severe adverse reaction experienced by some individuals to certain medicines commonly used in the treatment of cancer and osteoporosis (e.g. bisphosphonates, denosumab and antiangiogenic agents) and involves the progressive destruction of bone in the mandible or maxilla. Depending on the drug, its dosage, and the duration of exposure, the occurrence of this adverse drug reaction may be rare (e.g. following the oral administration of bisphosphonate or denosumab treatments for osteoporosis, or antiangiogenic agent-targeted cancer treatment) or common (e.g. following intravenous bisphosphonate for cancer treatment). MRONJ is associated with significant morbidity, adversely affects quality of life (QoL), and is challenging to treat. OBJECTIVES: To assess the effects of interventions versus no treatment, placebo, or an active control for the prophylaxis of MRONJ in people exposed to antiresorptive or antiangiogenic drugs.To assess the effects of non-surgical or surgical interventions (either singly or in combination) versus no treatment, placebo, or an active control for the treatment of people with manifest MRONJ. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 23 November 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, 2016, Issue 10), MEDLINE Ovid (1946 to 23 November 2016), and Embase Ovid (23 May 2016 to 23 November 2016). The US National Institutes of Health Trials Registry (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. No restrictions were placed on language or publication status when searching the electronic databases; however, the search of Embase was restricted to the last six months due to the Cochrane Embase Project to identify all clinical trials and add them to CENTRAL. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing one modality of intervention with another for the prevention or treatment of MRONJ. For 'prophylaxis of MRONJ', the primary outcome of interest was the incidence of MRONJ; secondary outcomes were QoL, time-to-event, and rate of complications and side effects of the intervention. For 'treatment of established MRONJ', the primary outcome of interest was healing of MRONJ; secondary outcomes were QoL, recurrence, and rate of complications and side effects of the intervention. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the search results, extracted the data, and assessed the risk of bias in the included studies. For dichotomous outcomes, we reported the risk ratio (RR) (or rate ratio) and 95% confidence intervals (CI). MAIN RESULTS: We included five RCTs (1218 participants) in the review. Three trials focused on the prophylaxis of MRONJ. Two trials investigated options for the treatment of established MRONJ. The RCTs included only participants treated with bisphosphonates and, thus, did not cover the entire spectrum of medications associated with MRONJ. Prophylaxis of MRONJOne trial compared standard care with regular dental examinations in three-month intervals and preventive treatments (including antibiotics before dental extractions and the use of techniques for wound closure that avoid exposure and contamination of bone) in men with metastatic prostate cancer treated with zoledronic acid. The intervention seemed to lower the risk of MRONJ: RR 0.10; 95% CI 0.02 to 0.39 (253 participants; low quality evidence). Secondary outcomes were not evaluated.As dentoalveolar surgery is considered a common predisposing event for developing MRONJ, one trial investigated the effect of plasma rich in growth factors (PRGF) for preventing MRONJ in people with cancer undergoing dental extractions. There was insufficient evidence to support or refute a benefit of PRGF on MRONJ incidence when compared with standard treatment (RR 0.08, 95% CI 0.00 to 1.51; 176 participants; very low quality evidence). Secondary outcomes were not reported. In another trial comparing wound closure by primary intention with wound closure by secondary intention after dental extractions in people treated with oral bisphosphonates (700 participants), no cases of intraoperative complications or postoperative MRONJ were observed. QoL was not investigated. Treatment of MRONJOne trial analysed hyperbaric oxygen (HBO) treatment used in addition to standard care (antiseptic rinses, antibiotics, and surgery) compared with standard care alone. HBO in addition to standard care did not significantly improve healing from MRONJ compared with standard care alone (at last follow-up: RR 1.56; 95% CI 0.77 to 3.18; 46 participants included in the analysis; very low-quality evidence). QoL data were presented qualitatively as intragroup comparisons; hence, an effect estimate of treatment on QoL was not possible. Other secondary outcomes were not reported.The other RCT found no significant difference between autofluorescence- and tetracycline fluorescence-guided sequestrectomy for the surgical treatment of MRONJ at any timepoint (at one-year follow-up: RR 1.05; 95% CI 0.86 to 1.30; 34 participants included in the analysis; very low-quality evidence). Secondary outcomes were not reported. AUTHORS' CONCLUSIONS: Prophylaxis of MRONJOne open label RCT provided some evidence that dental examinations in three-month intervals and preventive treatments may be more effective than standard care for reducing the incidence of MRONJ in individuals taking intravenous bisphosphonates for advanced cancer. We assessed the certainty of the evidence to be low.There is insufficient evidence to either claim or refute a benefit of either of the interventions tested for prophylaxis of MRONJ (i.e. PRGF inserted into the postextraction alveolus during dental extractions, and wound closure by primary or secondary intention after dental extractions). Treatment of MRONJAvailable evidence is insufficient to either claim or refute a benefit for hyperbaric oxygen therapy as an adjunct to conventional therapy. There is also insufficient evidence to draw conclusions about autofluorescence-guided versus tetracycline fluorescence-guided bone surgery. PMID- 28983910 TI - 'Your lack of planning does not constitute my emergency' - caring for obstetric patients with mental illness. PMID- 28983909 TI - Anthropometric factors and cutaneous melanoma: Prospective data from the population-based Janus Cohort. AB - The aim of the present study was to prospectively examine risk of cutaneous melanoma (CM) according to measured anthropometric factors, adjusted for exposure to ultraviolet radiation (UVR), in a large population-based cohort in Norway. The Janus Cohort, including 292,851 Norwegians recruited 1972-2003, was linked to the Cancer Registry of Norway and followed for CM through 2014. Cox regression was used to estimate hazard ratios (HRs) of CM with 95% confidence intervals (CIs). Restricted cubic splines were incorporated into the Cox models to assess possible non-linear relationships. All analyses were adjusted for attained age, indicators of UVR exposure, education, and smoking status. During a mean follow-up of 27 years, 3,000 incident CM cases were identified. In men, CM risk was positively associated with body mass index, body surface area (BSA), height and weight (all ptrends < 0.001), and the exposure-response curves indicated an exponential increase in risk for all anthropometric factors. Weight loss of more than 2 kg in men was associated with a 53% lower risk (HR 0.47, 95% CI: 0.39, 0.57). In women, CM risk increased with increasing BSA (ptrend = 0.002) and height (ptrend < 0.001). The shape of the height-CM risk curve indicated an exponential increase. Our study suggests that large body size, in general, is a CM risk factor in men, and is the first to report that weight loss may reduce the risk of CM among men. PMID- 28983911 TI - Global Regulatory Differences for Gene- and Cell-Based Therapies: Consequences and Implications for Patient Access and Therapeutic Innovation. AB - Gene- and cell-based therapies (GCTs) offer potential new treatment options for unmet medical needs. However, the use of conventional regulatory requirements for medicinal products to approve GCTs may impede patient access and therapeutic innovation. Furthermore, requirements differ between jurisdictions, complicating the global regulatory landscape. We provide a comparative overview of regulatory requirements for GCT approval in five jurisdictions and hypothesize on the consequences of the observed global differences on patient access and therapeutic innovation. PMID- 28983913 TI - Multiple dimensions of intraspecific diversity affect biomass of eelgrass and its associated community. AB - Genetic diversity within key species can play an important role in the functioning of entire communities. However, the extent to which different dimensions of diversity (e.g., the number of genotypes vs. the extent of genetic differentiation among those genotypes) best predicts functioning is unknown and may yield clues into the different mechanisms underlying diversity effects. We explicitly test the relative influence of genotypic richness and genetic relatedness on eelgrass productivity, biomass, and the diversity of associated invertebrate grazers in a factorial field experiment using the seagrass species, Zostera marina (eelgrass). Genotypic richness had the strongest effect on eelgrass biomass accumulation, such that plots with more genotypes at the end of the experiment attained a higher biomass. Genotypic diversity (richness + evenness) was a stronger predictor of biomass than richness alone, and both genotype richness and diversity were positively correlated with trait diversity. The relatedness of genotypes in a plot reduced eelgrass biomass independently of richness. Plots containing eelgrass with greater trait diversity also had a higher abundance of invertebrate grazers, while the diversity and relatedness of eelgrass genotypes had little effect on invertebrate abundance or richness. Our work extends previous findings by explicitly relating genotypic diversity to trait diversity, thus mechanistically connecting genotypic diversity to plot level yields. We also show that other dimensions of diversity, namely relatedness, influence eelgrass performance independent of trait differentiation. Ultimately, richness and relatedness captured fundamentally different components of intraspecific variation and should be treated as complementary rather than competing dimensions of biodiversity affecting ecosystem functioning. PMID- 28983912 TI - The impact of bottlenecks on microbial survival, adaptation, and phenotypic switching in host-pathogen interactions. AB - Microbial pathogens and viruses can often maintain sufficient population diversity to evade a wide range of host immune responses. However, when populations experience bottlenecks, as occurs frequently during initiation of new infections, pathogens require specialized mechanisms to regenerate diversity. We address the evolution of such mechanisms, known as stochastic phenotype switches, which are prevalent in pathogenic bacteria. We analyze a model of pathogen diversification in a changing host environment that accounts for selective bottlenecks, wherein different phenotypes have distinct transmission probabilities between hosts. We show that under stringent bottlenecks, such that only one phenotype can initiate new infections, there exists a threshold stochastic switching rate below which all pathogen lineages go extinct, and above which survival is a near certainty. We determine how quickly stochastic switching rates can evolve by computing a fitness landscape for the evolutionary dynamics of switching rates, and analyzing its dependence on both the stringency of bottlenecks and the duration of within-host growth periods. We show that increasing the stringency of bottlenecks or decreasing the period of growth results in faster adaptation of switching rates. Our model provides strong theoretical evidence that bottlenecks play a critical role in accelerating the evolutionary dynamics of pathogens. PMID- 28983914 TI - Crystal structure and functional characterization of SF216 from Shigella flexneri. AB - Shigella flexneri is a Gram-negative anaerobic bacterium that causes highly infectious bacterial dysentery in humans. Here, we solved the crystal structure of SF216, a hypothetical protein from the S. flexneri 5a strain M90T, at 1.7 A resolution. The crystal structure of SF216 represents a homotrimer stabilized by intersubunit interactions and ion-mediated electrostatic interactions. Each subunit consists of three beta-strands and five alpha-helices with the beta-beta beta-alpha-alpha-alpha-alpha-alpha topology. Based on the structural information, we also demonstrate that SF216 shows weak ribonuclease activity by a fluorescence quenching assay. Furthermore, we identify potential druggable pockets (putative hot spots) on the surface of the SF216 structure by computational mapping. PMID- 28983915 TI - Hypothesis - buttressed rings assemble, clamp, and release SNAREpins for synaptic transmission. AB - Neural networks are optimized to detect temporal coincidence on the millisecond timescale. Here, we offer a synthetic hypothesis based on recent structural insights into SNAREs and the C2 domain proteins to explain how synaptic transmission can keep this pace. We suggest that an outer ring of up to six curved Munc13 'MUN' domains transiently anchored to the plasma membrane via its flanking domains surrounds a stable inner ring comprised of synaptotagmin C2 domains to serve as a work-bench on which SNAREpins are templated. This 'buttressed-ring hypothesis' affords straightforward answers to many principal and long-standing questions concerning how SNAREpins can be assembled, clamped, and then released synchronously with an action potential. PMID- 28983916 TI - PIEZO2 as the anomalous mechanotransducer channel in auditory hair cells. AB - Throughout postnatal maturation of the mouse inner ear, cochlear hair cells display at least two types of mechanically gated ion channel: normal mechanotransducer (MT) channels at the tips of the stereocilia, activated by tension in interciliary tip links, and anomalous mechanosensitive (MS) channels on the top surface of the cells. The anomalous MS channels are responsible for the reverse-polarity current that appears in mutants in which normal transduction is lost. They are also seen in wild-type hair cells around birth, appearing 2 days earlier than normal MT channels, and being down-regulated with the emergence of the normal channels. We review the evidence that the normal and anomalous channels are distinct channel types, which includes differences in localization, susceptibility to pharmacological agents, single-channel conductance and Ca2+ permeability. The dichotomy is reinforced by the observation that the anomalous current is absent in cochlear cells of Piezo2-null mice, even though the normal MT current persists. The anomalous current is suppressed by high intracellular Ca2+ , suggesting that influx of the divalent ion via more Ca2+ -permeable normal MT channels inhibits the anomalous channels, thus explaining the temporal relationship between the two. Piezo2-null mice have largely normal hearing, exhibiting up to 20 dB elevation in threshold in the acoustic brainstem response, so raising questions about the significance of PIEZO2 in the cochlea. Since the anomalous current declines with postnatal age, PIEZO2 may contribute to hair cell development, but it does not underlie the normal MT current. Its role in the development of hearing is not understood. PMID- 28983917 TI - Influence of the location and type of epileptogenic lesion on scalp interictal epileptiform discharges and high-frequency oscillations. AB - OBJECTIVE: To increase the diagnostic power of scalp electroencephalography (EEG) by investigating whether lesion type and location influence the morphology of interictal epileptic discharges (IEDs) and the likelihood that IEDs and high frequency oscillations (HFOs) are present. METHODS: We studied EEG activity in epilepsy patients with lesional epilepsy. Lesions were classified by type and by location (region and depth). We marked a maximum of 50 IEDs during deep non-rapid eye movement sleep. IEDs were identified as spikes or sharp waves with or without slow waves, or bursts of spikes or sharp waves with or without slow waves. We analyzed HFOs in the studies showing at least 50 IEDs. RESULTS: In 192 scalp EEG studies, the differences in the percentage of studies showing IEDs in each depth related group were not statistically significant, whereas HFOs (55 studies) predominated in patients exhibiting superficial lesions (p<0.001). Sharp waves, as predominant pattern, were more prevalent in hippocampal abnormalities (p < 0.001), whereas bursts predominated in patients with malformations of cortical development (p < 0.001). SIGNIFICANCE: The depth of the lesion does not influence the presence of IEDs, as one might expect, but it influences that of HFOs. This is explained as follows. HFOs are generated in the epileptogenic region, do not propagate, and hence are only visible on scalp EEG with superficial lesions. IEDs can result from a nearby focus or propagate from a deep generator and are therefore equally present with deep, intermediate, and superficial lesions. Additionally, IED morphology provides information in determining the lesion type. PMID- 28983918 TI - How many cancer cases and deaths are potentially preventable? Estimates for Australia in 2013. AB - Cancer is a leading cause of disease burden in Australia, particularly fatal burden, accounting for an estimated thirty percent of deaths. Many cancers develop because of exposure to lifestyle and environmental factors that are potentially modifiable. We aimed to quantify the proportions and numbers of cancer deaths and cases in Australia in 2013 attributable to 20 modifiable factors in eight broad groupings that are established causes of cancer, namely: tobacco smoke (smoking and second-hand), dietary factors (low intake of fruit, non-starchy vegetables and dietary fibre; and high intake of red and processed meat), overweight/obesity, alcohol, physical inactivity, solar ultraviolet radiation, infections (seven agents), and reproductive factors (lack of breastfeeding, menopausal hormone therapy use, combined oral contraceptive use). We estimated population attributable fractions (PAF) using standard formulae incorporating exposure prevalence and relative risk data. Of all cancer deaths in Australia in 2013, approximately 38% overall (males 41%, females 34%) could be attributed to the factors assessed; the corresponding PAF for cancer cases was 33% (males 34%, females 32%). Tobacco smoke was the leading cause of cancer deaths and cases, with PAFs of 23 and 13%, respectively, followed by dietary factors (5% deaths/5% cases), overweight/obesity (5%/4%) and infections (5%/3%). Cancer sites with the highest numbers of potentially preventable deaths/cases were lung (n = 6,776/9,272), colorectum (n = 1,974/7,380) and cutaneous melanoma (n = 1,390/7,918). We estimate that about 16,700 cancer deaths and 41,200 cancer cases could be prevented in Australia each year if people's exposures to 20 causal factors were aligned with levels recommended to minimise cancer risk. PMID- 28983919 TI - Role of stem cell derived exosomes in tumor biology. AB - Exosomes are nano-scale messengers loaded with bio-molecular cargo of RNA, DNA, and Proteins. As a master regulator of cellular signaling, stem cell (both normal, and cancer stem cells) secreted exosome orchestrate various autocrine and paracrine functions which alter tumor micro-environment, growth and progression. Exosomes secreted by one of the two important stem cell phenotypes in cancers a) Mesenchymal stem cells, and b) Cancer stem cells not only promote cancerous growth but also impart therapy resistance in cancer cells. In tumors, normal or mesenchymal stem cell (MSCs) derived exosomes (MSC-exo) modulate tumor hallmarks by delivering unique miRNA species to neighboring cells and help in tumor progression. Apart from regulating tumor cell fate, MSC-exo are also capable of inducing physiological processes, for example, angiogenesis, metastasis and so forth. Similarly, cancer stem cells (CSCs) derived exosomes (CSC-exo) contain stemness-specific proteins, self-renewal promoting regulatory miRNAs, and survival factors. CSC-exo specific cargo maintains tumor heterogeneity and alters tumor progression. In this review we critically discuss the importance of stem cell specific exosomes in tumor cell signaling pathways with their role in tumor biology. PMID- 28983920 TI - Transcriptional variations in the wider peritumoral tissue environment of pancreatic cancer. AB - Transcriptional profiling was performed on 452 RNA preparations isolated from various types of pancreatic tissue from tumour patients and healthy donors, with a particular focus on peritumoral samples. Pancreatic ductal adenocarcinomas (PDAC) and cystic tumours were most different in these non-tumorous tissues surrounding them, whereas the actual tumours exhibited rather similar transcript patterns. The environment of cystic tumours was transcriptionally nearly identical to normal pancreas tissue. In contrast, the tissue around PDAC behaved a lot like the tumour, indicating some kind of field defect, while showing far less molecular resemblance to both chronic pancreatitis and healthy tissue. This suggests that the major pathogenic difference between cystic and ductal tumours may be due to their cellular environment rather than the few variations between the tumours. Lack of correlation between DNA methylation and transcript levels makes it unlikely that the observed field defect in the peritumoral tissue of PDAC is controlled to a large extent by such epigenetic regulation. Functionally, a strikingly large number of autophagy-related transcripts was changed in both PDAC and its peritumoral tissue, but not in other pancreatic tumours. A transcription signature of 15 autophagy-related genes was established that permits a prognosis of survival with high accuracy and indicates the role of autophagy in tumour biology. PMID- 28983921 TI - Epileptogenic networks in nodular heterotopia: A stereoelectroencephalography study. AB - OBJECTIVE: Defining the roles of heterotopic and normotopic cortex in the epileptogenic networks in patients with nodular heterotopia is challenging. To elucidate this issue, we compared heterotopic and normotopic cortex using quantitative signal analysis on stereoelectroencephalography (SEEG) recordings. METHODS: Clinically relevant biomarkers of epileptogenicity during ictal (epileptogenicity index; EI) and interictal recordings (high-frequency oscillation and spike) were evaluated in 19 patients undergoing SEEG. These biomarkers were then compared between heterotopic cortex and neocortical regions. Seizures were classified as normotopic, heterotopic, or normoheterotopic according to respective values of quantitative analysis (EI >=0.3). RESULTS: A total of 1,246 contacts were analyzed: 259 in heterotopic tissue (heterotopic cortex), 873 in neocortex in the same lobe of the lesion (local neocortex), and 114 in neocortex distant from the lesion (distant neocortex). No significant difference in EI values, high-frequency oscillations, and spike rate was found comparing local neocortex and heterotopic cortex at a patient level, but local neocortex appears more epileptogenic (p < 0.001) than heterotopic cortex analyzing EI values at a seizure level. According to EI values, seizures were mostly normotopic (48.5%) or normoheterotopic (45.5%); only 6% were purely heterotopic. A good long-term treatment response was obtained in only two patients after thermocoagulation and surgical disconnection. SIGNIFICANCE: This is the first quantitative SEEG study providing insight into the mechanisms generating seizures in nodular heterotopia. We demonstrate that both the heterotopic lesion and particularly the normotopic cortex are involved in the epileptogenic network. This could open new perspectives on multitarget treatments, other than resective surgery, aimed at modifying the epileptic network. PMID- 28983922 TI - A psychometric evaluation of the Temperament in Middle Childhood Questionnaire (TMCQ) in a Swedish sample. AB - Personality is generally considered to be biologically founded in temperament, and temperamental qualities have proven to be relatively stable across childhood and into adulthood (Caspi, Roberts & Shiner, ). Temperament predicts important developmental outcomes such as academic performance (Muris, ), and social functioning (Eisenberg, Fabes, Guthrie & Reiser, ), and it has also been found to be strongly related to the etiology and maintenance of internalizing and externalizing psychopathology in children (Muris, Meesters & Blijlevens, ; Nigg, ). To allow for the possibility of making early interventions, identification of potential risk factors (such as temperamental dispositions) is of great importance (Rettew & McKee, ). As temperament is multidimensional and has many different manifestations, parents and teachers are valuable sources in providing information about children's temperament (Rothbart & Bates, ; Tackett, Slobodskaya, Mar et al., ), and caregiver questionnaires are frequently used in child personality research. However, such questionnaires are only useful if their reliability and validity have been established. The aim of the present study was to examine the psychometric properties of the Temperament in Middle Childhood Questionnaire (TMCQ; Simonds, Kieras, Rueda & Rothbart, ), which focuses specifically on the ages between 7 and 11 years. The TMCQ is the least validated of the Rothbart measures, and although reliability data have been presented, together with some validity data, for a computerized self-report version of the questionnaire (Simonds & Rothbart, ), information about the reliability and validity for the caregiver version is scant. In the present paper, we report such data for a Swedish sample. PMID- 28983924 TI - Symmetry and stimulus class formation in humans: Control by temporal location in a successive matching task. AB - Symmetry refers to the observation that subjects will derive B-A (e.g., in the presence of B, select A) after being trained on A-B (e.g., in the presence of A, select B). Whereas symmetry is readily shown in humans, it has been difficult to demonstrate in nonhuman animals. This difficulty, at least in pigeons, may result from responding to specific stimulus properties that change when sample and comparison stimuli switch roles between training and testing. In three experiments with humans, we investigated to what extent human responding is influenced by the temporal location of stimuli using a successive matching-to sample procedure. Our results indicate that temporal location does not spontaneously control responding in humans, although it does in pigeons. Therefore, the number of functional stimuli that humans respond to in this procedure may be half of the number of functional stimuli that the pigeons respond to. In a fourth experiment, we tested this assumption by doubling the number of functional stimuli controlling responding in human participants in an attempt to make the test more comparable to symmetry tests with pigeons. Here, we found that humans responded according to indirect class formation in the same manner as pigeons do. In sum, our results indicate that functional symmetry is readily observed in humans, even in cases where the temporal features of the stimuli prevent functional symmetry in pigeons. We argue that this difference in behavior between the two species does not necessarily reflect a difference in capacity to show functional symmetry between both species, but could also reflect a difference in the functional stimuli each species responds to. PMID- 28983923 TI - The highs and lows of programmed cardiovascular disease by developmental hypoxia: studies in the chicken embryo. AB - It is now established that adverse conditions during pregnancy can trigger a fetal origin of cardiovascular dysfunction and/or increase the risk of heart disease in later life. Suboptimal environmental conditions during early life that may promote the development of cardiovascular dysfunction in the offspring include alterations in fetal oxygenation and nutrition as well as fetal exposure to stress hormones, such as glucocorticoids. There has been growing interest in identifying the partial contributions of each of these stressors to programming of cardiovascular dysfunction. However, in humans and in many animal models this is difficult, as the challenges cannot be disentangled. By using the chicken embryo as an animal model, science has been able to circumvent a number of problems. In contrast to mammals, in the chicken embryo the effects on the developing cardiovascular system of changes in oxygenation, nutrition or stress hormones can be isolated and determined directly, independent of changes in the maternal or placental physiology. In this review, we summarise studies that have exploited the chicken embryo model to determine the effects on prenatal growth, cardiovascular development and pituitary-adrenal function of isolated chronic developmental hypoxia. PMID- 28983925 TI - A genome-wide significant association on chromosome 2 for footrot resistance/susceptibility in Swiss White Alpine sheep. AB - Footrot is one of the most important causes of lameness in global sheep populations and is characterized by a bacterial infection of the interdigital skin. As a multifactorial disease, its clinical representation depends not only on pathogen factors and environmental components but also on the individual resistance/susceptibility of the host. A genetic component has been shown in previous studies; however, so far no causative genetic variant influencing the risk of developing footrot has been identified. In this study, we genotyped 373 Swiss White Alpine sheep, using the ovine high-density 600k SNP chip, in order to run a DNA-based comparison of individuals with known clinical footrot status. We performed a case-control genome-wide association study, which revealed a genome wide significant association for SNP rs418747104 on ovine chromosome 2 at 81.2 Mb. The three best associated SNP markers were located at the MPDZ gene, which codes for the multiple PDZ domain crumbs cell polarity complex component protein, also known as multi-PDZ domain protein 1 (MUPP1). This protein is possibly involved in maintaining the barrier function and integrity of tight junctions. Therefore, we speculate that individuals carrying MPDZ variants may differ in their footrot resistance/susceptibility due to modified horn and interdigital skin integrity. In conclusion, our study reveals that MPDZ might represent a functional candidate gene, and further research is needed to explore its role in footrot affected sheep. PMID- 28983927 TI - When less is more: Psychometric properties of Norwegian short-forms of the Ambivalent Sexism Scales (ASI and AMI) and the Illinois Rape Myth Acceptance (IRMA) Scale. AB - This paper reports on the development and the psychometric properties of short forms of Ambivalent Sexism Scales toward women (ASI; Glick & Fiske, 1996) and men (AMI; Glick & Fiske, 1999), and a scale measuring rape stereotypes (IRMA; McMahon & Farmer, 2011). The short form AMI/ASI were applied for examining gender and educational differences in university students (N = 512) and in high school students (N = 1381), and for predicting individual differences in rape stereotypes in the latter. The short forms demonstrated good to excellent psychometric properties across samples of emerging adults. Relative to female students, male students reported markedly more hostility toward women and more stereotypical beliefs about rape. Despite sampling from a highly gender egalitarian and secular culture, these gender differences are on a par with those reported internationally. Rape stereotypes were predicted by sexism in high school students. Additional predictors were educational program, relationship status, and acceptance of derogatory sexual slurs. The paper questions the validity of separate constructs for benevolent sexism toward women versus men. The short form versions of the scales may substitute the original versions in future research, and help prevent attrition while measuring the same constructs. PMID- 28983926 TI - The PAC-SYM questionnaire for chronic constipation: defining the minimal important difference. AB - BACKGROUND: The Patient Assessment of Constipation-Symptoms (PAC-SYM) questionnaire is frequently used in clinical trials of constipation. However, the threshold for reduction in total PAC-SYM score used to define a clinical response on this 0-4 point scale has not undergone formal appraisal, and its relationship with clinical benefit as perceived by patients has not been defined. AIM: To determine the minimal important difference in PAC-SYM score, and the optimum cut off value for defining responders. METHODS: The minimal important difference was estimated using data from six international phase 3/4, double-blind, randomised controlled trials of prucalopride in patients with chronic constipation (NCT01147926, NCT01424228, NCT01116206, NCT00485940, NCT00483886, NCT00488137), with anchor- and distribution-based approaches. Five appropriate patient-reported outcomes were selected as anchors. In addition, receiver operating characteristics (ROC) curve analyses were used to investigate responder discrimination for each anchor. RESULTS: Data from 2884 patients were included. Minimal important difference estimates ranged from -0.52 to -0.63 across the five anchors. Estimates were not affected by study location but were consistently lower for rectal symptoms than for abdominal and stool symptoms. Distribution based estimates were considerably lower than anchor-based estimates. ROC curve analyses showed optimum cut-off scores for discriminating responders to be similar to anchor-based minimal important difference estimates. CONCLUSIONS: Anchor-based methods gave consistent results for the minimal important difference, at approximately -0.6, and this value was close to the ROC-determined optimal cut-off scores for responder discrimination. This value could be considered in clinical practice. A slightly more conservative threshold (eg 0.75) could be used in clinical trials to reduce the placebo response rate. PMID- 28983928 TI - Highly identified power-holders feel responsible: The interplay between social identification and social power within groups. AB - Power relations affect dynamics within groups. Power-holders' decisions not only determine their personal outcomes, but also the outcomes of others in the group that they control. Yet, power-holders often tend to overlook this responsibility to take care of collective interests. The present research investigated how social identification - with the group to which both the powerful and the powerless belong - alters perceived responsibility among power-holders (and the powerless). Combining research on social power and social identity, we argue that power-holders perceive more responsibility than the powerless when strongly (rather than when weakly) identifying with the group. A study among leaders and an experiment supported this, highlighting that although power-holders are often primarily concerned about personal outcomes, they do feel responsible for considering others' interests when these others are included in the (social) self. PMID- 28983929 TI - Sleep problems in prison employees. PMID- 28983930 TI - Safety of leucodepleted salvaged blood in oncological surgery: an in vitro model. AB - Intra-operative blood cell salvage (IOCS) is mainly avoided in onco surgery due to the suspicion that it could increase metastasis' risk. We simulated IOCS followed by leucodepletion: HCT116 (human colorectal cancer) cells were inoculated into packed red blood cells units, and their distribution was evaluated, step-by-step, by flow cytometry and immunohistochemistry. Most of HCT116 cells were lost during washing, and almost completely removed after filtration. IOCS plus leucodepletion could be of great advantage for oncological patients, where allogenic blood transfusion could influence tumour progression. PMID- 28983931 TI - Two brown coat colour-associated TYRP1 variants (bc and bd ) occur in Leonberger dogs. PMID- 28983932 TI - Ecological and Evolutionary Benefits of Temperate Phage: What Does or Doesn't Kill You Makes You Stronger. AB - Infection by a temperate phage can lead to death of the bacterial cell, but sometimes these phages integrate into the bacterial chromosome, offering the potential for a more long-lasting relationship to be established. Here we define three major ecological and evolutionary benefits of temperate phage for bacteria: as agents of horizontal gene transfer (HGT), as sources of genetic variation for evolutionary innovation, and as weapons of bacterial competition. We suggest that a coevolutionary perspective is required to understand the roles of temperate phages in bacterial populations. PMID- 28983933 TI - Effect of orally administered vibrio bacterin on immunity, survival and growth in tiger shrimp (Penaeus monodon) grow-out culture ponds. AB - : Vibriosis is one of the important diseases causing economic loss to the shrimp industry worldwide. The present study reports field observations on the immune stimulatory effect of vibrio bacterin in commercial tiger shrimp (Penaeus monodon) grow-out culture ponds (n = 62) which were grouped under three stocking densities; low (6-8 nos per m2 ), medium (9-11 nos per m2 ) and high (12-14 nos per m2 ). The bacterin was administered in feed as a top dressing at final concentration equivalent to 2 * 108 CFU per kilogram feed twice a week throughout the culture period. In 20 representative ponds, total haemocyte count and prophenoloxidase activity in shrimp were significantly (P < 0.05) higher and anatomical deformities like, antennae cut (5.02 +/- 2.42), tail rot (5.10 +/- 1.74), rostrum cut (4.49 +/- 2.19) and soft shell (10.05 +/- 5.77) were significantly lower compared to controls in all the studied stocking densities. Significant (P < 0.05) improvement in production parameters like survival and production (kg ha1 ) was observed in all treatment ponds while similar improvement in average daily gain and feed conversion ratio could be observed in groups with low and medium stocking densities. Results of the study suggest that, oral administration of vibrio bacterin improves the immunity, reduces anatomical deformities and enhances the production in commercial shrimp culture operations. SIGNIFICANCE AND IMPACT OF THE STUDY: Administration of vibrio bacterin in feed as a top dressing induced immune stimulation as indicated by higher levels of total haemocyte count and prophenoloxidase. Further reduction in percentage of animals with anatomical deformities suggests the protection against subclinical bacterial infections. The overall improvement in the production parameters like, average daily gain, survival, feed conversation ratio and production in different shrimp stocking densities under commercial farming conditions suggested the possible development of an immune stimulant product based on the inactivated vibrio bacteria for improved health and production in Penaeus monodon shrimp farming. PMID- 28983934 TI - Free dug concentrations in pregnancy: Bound to measure unbound? PMID- 28983935 TI - Semiparametric accelerated failure time cure rate mixture models with competing risks. AB - Modern medical treatments have substantially improved survival rates for many chronic diseases and have generated considerable interest in developing cure fraction models for survival data with a non-ignorable cured proportion. Statistical analysis of such data may be further complicated by competing risks that involve multiple types of endpoints. Regression analysis of competing risks is typically undertaken via a proportional hazards model adapted on cause specific hazard or subdistribution hazard. In this article, we propose an alternative approach that treats competing events as distinct outcomes in a mixture. We consider semiparametric accelerated failure time models for the cause conditional survival function that are combined through a multinomial logistic model within the cure-mixture modeling framework. The cure-mixture approach to competing risks provides a means to determine the overall effect of a treatment and insights into how this treatment modifies the components of the mixture in the presence of a cure fraction. The regression and nonparametric parameters are estimated by a nonparametric kernel-based maximum likelihood estimation method. Variance estimation is achieved through resampling methods for the kernel smoothed likelihood function. Simulation studies show that the procedures work well in practical settings. Application to a sarcoma study demonstrates the use of the proposed method for competing risk data with a cure fraction. PMID- 28983936 TI - Choice of clinical supervisor: Cunning or collusion? PMID- 28983937 TI - Factors associated with change in health-related quality of life among individuals treated with long-term mechanical ventilation, a 6-year follow-up study. AB - AIMS: To examine changes and explanatory variables for changes in health-related quality of life in patients treated with long-term mechanical ventilation over a 6-year period. BACKGROUND: Long-term mechanical ventilation is a treatment for individuals with chronic hypercapnic respiratory failure, primarily caused by neuromuscular diseases, obesity hypoventilation syndrome, chronic obstructive pulmonary and restrictive thoracic diseases. Studies on long-term outcome on health-related quality of life and factors influencing it are lacking. DESIGN: Prospective cohort study. METHODS: Data were collected from the Norwegian Long Term-Mechanical-Ventilation Registry and from patient-reported questionnaire in 2008 and 2014. Health-related quality of life was measured by the Severe Respiratory Insufficiency questionnaire, containing 49 items and seven subdomains. Linear mixed effects models were used to measure changes and identify factors for changes. RESULTS: After 6 years, 60 patients were still participating, out of 127 at baseline. Health-related quality of life improved significantly in the total score and in four subdomains of the questionnaire. Satisfaction with training in long-term mechanical ventilation was an explanatory variable for improved 'psychological well-being' and follow-up for improvement of 'anxiety'. Side effects of the treatment like facial soreness were associated with the total score. High age and high forced vital capacity were related to lower 'physical function' and improved 'social functioning', respectively. CONCLUSION: Long-term mechanical ventilation over 6 years improved health-related quality of life in most patients. Patient training, follow-up and reduction of side effects, largely delivered by trained nurses, contribute to achieve the main goal of the treatment-improved health-related quality of life. PMID- 28983938 TI - Effects of moisturizing skincare on skin barrier function and the prevention of skin problems in 3-month-old infants: A randomized controlled trial. AB - An effective newborn skincare protocol has not been established. We aimed to evaluate the effects of moisturizing skincare, including using lotion and reducing routine bathing. Our hypothesis was that moisturizing skincare would improve skin barrier function. This randomized controlled trial included 227 healthy Asian newborns between 1 week and 3 months old. We compared moisturizing skincare (bathing every 2 days and using lotion daily; intervention, n = 113) to daily bathing without lotion (control, n = 114). We assessed the skin barrier function (transepidermal water loss [TEWL], stratum corneum hydration [SCH], skin pH and sebum secretion) as a primary outcome at 3 months old. We also assessed the incidence of skin problems according to parents' diary reports. Compared with the control, the intervention group had a lower face TEWL (mean +/- standard deviation, 14.69 +/- 7.38 vs 17.08 +/- 8.26 g/m2 per h, P = 0.033), higher face SCH (60.38 +/- 13.66 vs 53.52 +/- 14.55, P = 0.001) and higher body SCH (58.89 +/ 12.96 vs 53.02 +/- 10.08, P < 0.001). Compared with the control, newborns in the intervention group had significantly lower rates of diaper dermatitis between birth and 1 month old (6.3% vs 15.9%, P = 0.022), and tended to have lower rates of body skin problems between 1 and 3 months (42.1% vs 55.2%, P = 0.064). Moisturizing skincare was effective for improving skin barrier function and preventing newborns' diaper dermatitis. The results of our study may help parents make informed decisions about newborn skincare. PMID- 28983939 TI - The association between pediatric injury risks and parenting behaviours. AB - BACKGROUND: Unintentional injuries are the leading cause of death in children ages 1-18 years. Many of these injuries to young children occur in their own homes. Although research has explored injury risk prevention strategies, historically, much of this research has focused on environmental changes and teaching safety practices. Currently, there appears to be a gap in current research exploring how parenting influences children's risk of injury. METHODS: Mothers (n = 119) of children 5 years and younger were recruited from a paediatric clinic as a part of a larger study and completed measures of parenting challenges, developmentally sensitive parenting, child neglect, parental efficacy, and risk of potential injury situations. Hierarchical logistic regression was used to explore the extent to which developmentally insensitive parenting behaviours put parents at higher risk for behaviours that lead to unintentional injury in children and whether developmentally sensitive parenting behaviours protects children from injury. The association between demographic characteristics and injury risk behaviours was also examined. RESULTS: Parents who reported more frequent insensitive parenting behaviours (i.e., yelling, spanking, and putting child in time out) were more likely to report putting their child in an incorrect car seat or taking their child out of a car seat while the car is still moving. In addition, younger parents were at greater risk of storing cleaners and medications unsafely. CONCLUSION: Results from this study highlight the importance of supporting younger mothers and educating parents on effective parenting strategies when trying to prevent unintentional injury risks. PMID- 28983940 TI - Outline of guidelines for the management of vasculitis and vascular disorders in Japan, 2016 revised edition. AB - The proposal by the 1994 International Chapel Hill Consensus Conference on the Nomenclature of Systemic Vasculitides (CHCC1994) and by the CHCC2012 markedly influenced the classification and way of considering cutaneous vasculitis. In the proposal by the CHCC1994, hypersensitivity angiitis was defined as an equivalent pathological condition to microscopic polyangiitis or cutaneous leukocytoclastic angiitis (CLA), and it was not adopted as a disease name. However, CLA which was positioned as a type of small-vessel vasculitis is only a pathological name. In the proposal by the CHCC2012, a new category of single-organ vasculitis included CLA and cutaneous arteritis. Vasculitis allergica cutis (Ruiter) corresponded to CLA and cutaneous polyarteritis nodosa corresponded to cutaneous arteritis. The Japanese Dermatological Association (JDA) prepared guidelines for the management of vasculitis and vascular disorders in 2008 based on the proposal by the CHCC1994 and their original viewpoint of dermatology. The JDA subsequently revised the 2008 edition guidelines in 2016 following publication of the proposal of the CHCC2012 in Japanese. We presented the outline of the 2016 edition guidelines and propose a treatment algorithm for primary vasculitides based on the evaluation of the cutaneous symptoms for cases suspected as primary cutaneous vasculitides, which integrates the 2008 JDA guideline and CHCC2012 classification. This is the secondary English version of the original Japanese manuscript for the guideline for management of vasculitis and vascular disorders published in the Japanese Journal of Dermatology 127(3); 299-415, 2017. PMID- 28983941 TI - Impact of screening and exclusion of high anti-A titer donors on the risk of hemolytic anemia with intravenous immunoglobulin treatment: A hospital-based cohort study in the US. PMID- 28983942 TI - Dentists' opinions on using digital technologies in dental practice. AB - OBJECTIVES: To investigate which opinions among dentists are associated with level of technology use, when characteristics of the dentist and dental practice, as well as motivating work aspects are taken into account. METHODS: A total of 1000 general dental practitioners in the Netherlands received a questionnaire on digital technologies they use, opinions on using technologies and related motivating work aspects. Questions were derived from expert interviews, the Dentists' Experienced Job Resources Scale and literature on technology implementation. Technology use was measured as the number of technologies used, and divided into three technology user groups: low (using 0-4 technologies, mostly administrative and radiographic technologies), intermediate (using 5-7, more varied technologies) and high technology users (using 8-12, including more innovative diagnostic technologies). Opinions on technology use and motivating work aspects were analysed using principal components analysis (PCA) and exploratory factor analysis. Scores on all components and factors were calculated for each respondent by computing the mean of all valid responses on the underlying items. Differences in these scale scores on opinions among the technology user groups were assessed using one-way analysis of variance and Kruskal-Wallis tests. A multiple linear regression analysis assessed the association of scale scores about opinions on technology use with the sum of technologies used, taking into account motivating work aspects and characteristics of the dentist and dental practice. RESULTS: The response rate was 31%. Dentists who were high technology users perceived technologies as yielding more improvements in quality of care, adding more value to the dental practice and being easier to use, than low technology users. High technology users thought technologies added more value to their work and they reported higher skills and resources. They also focused more on technologies and thought these are more ready to use than low technology users. High technology users derived more motivation from "Immediate results" and "Craftsmanship" than low technology users. Personal and practice characteristics, motivating work aspects, and the opinion scales "Focus" and "Added value to dentist" explained 50% of the variance in the number of technologies a dentist uses. CONCLUSION: Opinions on digital technologies among dentists and motivating work aspects vary with level of technology use. Being more focused on technologies and perceiving a higher added value from using them are associated with using more digital dental technologies, when taking into account motivating work aspects and characteristics of the dentist and dental practice. PMID- 28983944 TI - Case of phenylephrine hydrochloride-induced periorbital contact dermatitis with fulminant keratoconjunctivitis causing pseudomembrane formation. PMID- 28983943 TI - Delayed methotrexate elimination: Incidence, interaction with antacid drugs, and clinical consequences? AB - The aim of this retrospective cohort study was to investigate the incidence of delayed methotrexate elimination in patients treated with high-dose methotrexate (>=1 g/m2 ) for haematological malignancy and to identify the impact of interacting drugs, especially proton-pump inhibitors (PPIs) and ranitidine. All patients treated with high-dose methotrexate over a 6 year period in the haematology department of the Lyon Sud University Hospital (Hospices Civils de Lyon, France) were included. Potential risk factors for delayed methotrexate elimination were tested in a generalized linear model by univariate analysis: patient age, gender, methotrexate dose, administration of PPI or ranitidine, and concomitant nephrotoxic drugs. A total of 412 cycles of methotrexate were administered to 179 patients. Proton-pump inhibitors were co-administered with methotrexate in 127 cycles and ranitidine in 192 cycles. Ninety-three cycles included no antacid drugs. A total of 918 plasma methotrexate assays were performed. Methotrexate concentrations were checked at 24 hours in 92% of cycles. Delayed methotrexate elimination was observed in 20.9% of cycles. A total of 63 cycles with delayed methotrexate elimination were only identified on plasma methotrexate measures at 72 hours: ie, plasma methotrexate was in the normal range at 24 and 48 hour post injection. Use of PPI/ranitidine or no antacid drugs did not increase risk of delayed elimination, with respectively delayed methotrexate elimination in 20.5%, 21.9%, and 19.4% of cycles (P = .89). Impaired baseline creatinine clearance showed significant association in univariate analysis. Fifteen patients showed grade 1 acute kidney injury, 1 grade 2, 2 grade 3, and none grade 4. For half of these cases, delayed methotrexate elimination was observed and the 2 grade 3 events appeared in patients treated with PPIs. This retrospective study suggests that there is no association between concomitant use of proton-pump inhibitors (pantoprazole and esomeprazole) or ranitidine and delayed methotrexate elimination. PMID- 28983945 TI - Association between promoter methylation of MLH1 and MSH2 and reactive oxygen species in oligozoospermic men-A pilot study. AB - MLH1 and MSH2 are important genes for DNA mismatch repair and crossing over during meiosis and are implicated in male infertility. Therefore, the methylation patterns of the DNA mismatch repair genes MLH1 and MSH2 in oligozoospermic males were investigated. Ten oligozoospermic patients and 29 normozoospermic donors were analysed. Methylation profiles of the MLH1 and MSH2 promotors were analysed. In addition, sperm motility and seminal reactive oxygen species (ROS) were recorded. Receiver operating characteristic (ROC) analysis was conducted to determine the accuracy of the DNA methylation status of MLH1 and MSH2 to distinguish between oligozoospermic and normozoospermic men. In oligozoospermic men, MLH1 was significantly (p = .0013) more methylated compared to normozoospermic men. Additionally, there was a significant positive association (r = .384; p = .0159) between seminal ROS levels and MLH1 methylation. Contrary, no association between MSH2 methylation and oligozoospermia was found. ROC curve analysis for methylation status of MLH1 was significant (p = .0275) with an area under the curve of 61.1%, a sensitivity of 22.2% and a specificity of 100.0%. This pilot study indicates oligozoospermic patients have more methylation of MLH1 than normozoospermic patients. Whether hypermethylation of the MLH1 promoter plays a role in repairing relevant mismatches of sperm DNA strands in idiopathic oligozoospermia warrants further investigation. PMID- 28983946 TI - Human papillomavirus type 6/11 identified in an epidermoid cyst of the scrotum. AB - To date, epidermoid cysts associated with human papillomavirus (HPV) infection have been described mainly in palmoplantar locations, and have involved HPV types 60 and 57. In contrast, HPV-6/11 is a major cause of condyloma acuminatum. Here, we report the case of a healthy 31-year-old man who presented to our clinic with a 1-month history of a 1-cm, reddish-brown, cystic scrotal tumor with a punctum. The lesion was studied histologically, immunohistochemically and by DNA-DNAin situ hybridization. Histology revealed an epidermoid cyst with vacuolated keratinocytes with shrunken nuclei (koilocytes) in the cyst wall. Immunostaining was positive for HPV antigens and in situ hybridization revealed HPV-6/11 DNA in the koilocytes. This is the first report of an HPV-6/11-associated epidermoid cyst in the anogenital skin of an immunocompetent individual. PMID- 28983947 TI - Correcting the cut-off point of hemoglobin at high altitude favors misclassification of anemia, erythrocytosis and excessive erythrocytosis. PMID- 28983948 TI - Severe erythema exudative multiforme developing from advanced melanoma treated with dabrafenib and trametinib followed by nivolumab. PMID- 28983949 TI - Improved prognosis with additional medium-dose VP16 to CY/TBI in allogeneic transplantation for high risk ALL in adults. AB - Allogeneic hematopoietic stem cell transplantation (HSCT) with the conventional cyclophosphamide and total body irradiation (CY/TBI) regimen is an essential therapeutic strategy for acute lymphoblastic leukemia (ALL) in adults. Medium dose etoposide (VP16, 30-40 mg/kg) can be added to intensify this CY/TBI regimen and reduce relapse; however, differences in prognosis between the VP16/CY/TBI and CY/TBI regimens have not yet been fully analyzed. We conducted a retrospective cohort study using a Japanese transplant registry database to compare the prognosis between the VP16/CY/TBI (VP16, total 30-40 mg/kg) (N = 376) and CY/TBI (N = 1178) regimens in adult patients with ALL transplanted at complete remission (CR) between January 1, 2000 and December 31, 2014. Our analyses indicated that VP16/CY/TBI significantly reduced relapse compared with CY/TBI (risk ratio, 0.75; 95% confidence interval [CI], 0.56-1.00; P = .05) with a corresponding improvement in leukemia-free survival (hazard ratio [HR], 0.76; 95%CI, 0.62-0.93; P = .01), particularly in patients transplanted at CR1 with advanced-risk (positive minimal residual disease, presence of poor-risk cytogenetics, or an initial elevated leukocyte count) (HR, 0.75; 95%CI, 0.56-1.00; P = .05) or those transplanted beyond CR2 (HR, 0.58; 95%CI, 0.39-0.88; P = .01). The addition of VP16 did not increase post-transplant complications or nonrelapse mortality (HR, 0.88; 95%CI, 0.65-1.18; P = .38). This study is the first to reveal the efficacy of the addition of medium-dose VP16 to CY/TBI in high-risk ALL. To establish new myeloablative conditioning regimens including VP16, a large-scale prospective study is necessary. PMID- 28983950 TI - Epidemiology and comorbidities of patients with chronic urticaria in Korea: A nationwide population-based study. AB - Few population-based studies have focused on the epidemiology and comorbidities of chronic urticaria (CU) or chronic spontaneous urticaria (CSU). The objective of this study was to obtain information on the epidemiology and comorbidities associated with CU and CSU in Korea. We conducted a cross-sectional analysis using a national health insurance database. An algorithm based on the International Classification of Diseases, 10th revision, was used for the identification of patients with CU and CSU, and an age-sex adjusted logistic regression model was used to assess the risk of comorbidities in these patients. The average annual prevalence rates of CU and CSU during the 4-year period between 2010 and 2013 were 3.08% and 1.40%, respectively. The prevalence rates of CU and CSU were higher in women than men (1:1.39 and 1:1.34, respectively) and peaked at 0-9 and 70-79 years, respectively. After adjustment for age and sex, the patients with CU and CSU were found to have a significantly higher prevalence rate of CU/CSU-related diseases, compared with those without CU (mean adjusted odds ratio, 8.46; 95% confidence interval, 8.10-8.83). Allergic rhinitis, drug allergies, asthma, thyroid diseases and cancers were the most common comorbidities. Stomach, thyroid, liver and prostate cancers were the most prevalent cancers. This study provides large epidemiological data on the prevalence rates of CU and CSU, and their comorbidities, in Korea. Patients with CU and CSU impose a higher burden, in terms of specific comorbidities, than those without CU. PMID- 28983951 TI - Development of a Cerebral Palsy Follow-up Registry in Jordan (CPUP-Jordan). AB - AIMS: This study aims to describe the development of a Cerebral Palsy Follow-up Registry in Jordan (CPUP-Jordan) and to provide a baseline child and parent demographic information, birth history of the child participants, and distribution of the participants based on topographical distribution of cerebral palsy (CP) and functional classification systems. METHODS: The CPUP-Jordan was developed using a similar framework of a follow-up surveillance programme for persons with CP in Sweden (CPUP). Standard assessment forms were utilized to collect data related to child and family demographics, child birth history, and functional classifications and physiotherapy and occupational therapy assessments and interventions. Research assistants were trained to conduct the assessments. A secured web-based system was developed to store data and disseminate knowledge maintained in the registry. Children with CP were included in the registry if they have confirmed diagnosis of CP. The ascertainment age of inclusion and the minimum age of survival required are 4 years. RESULTS: One hundred sixty-seven children were registered between 2013 and 2015 (mean age is 3.6 +/- 3.0 years). Forty-two percent were born premature, and 48% were less than the normal birthweight. Perinatal causes were reported for 54% of the participants. The most common type of CP based on tone disturbance was spastic type, and the most common topographical distributions of motor dysfunction were quadriplegia followed by diplegia. Fifty-six percent of the participants had severe limitation in ambulation; 48% had restricted manual abilities, and 47% had limited communication abilities even with familiar family members and partners. CONCLUSIONS: The development of CPUP-Jordan registry for children with CP proved to be both feasible and informative. The registry baseline descriptive data were similar to those reported in previous research in Jordan supporting validity of the data. The implementation of CPUP-Jordan at national level is expected to have a positive impact on children with CP, clinicians, policymakers, and researchers. PMID- 28983952 TI - General and professional values of student nurses and nurse educators. AB - AIM: The aim of this study was to explore and compare the self-reported general and professional values in undergraduate student nurses and nurse educators in Lithuania. BACKGROUND: Contemporary nursing requires strong moral motivation and clear values as nurses confront many ethical dilemas in their practice. Students acquire essential values of the nursing profession through the appropriate role modelling of their educators. Nursing students seek to become capable in providing ethical and professional patient care while their educators attempt to model desired behaviours. DESIGN: A national cross-sectional comparative study was carried out in March 2011. Four-hundred eight respondents participated: 316 undergraduate nursing students and 92 nurse educators. METHODS: A 57-item questionnaire was delivered to nursing programs at three universities and six colleges. Permission to conduct the study was granted by The Center on Bioethics. RESULTS: Student nurses and their educators rated the general value of altruism equally. Educators, in comparison with students, ranked honesty and intellectualism significantly higher and more often admired truth-telling in any circumstance. Students were more likely to avoid intellectual challenges in reading and placed lower importance on academic qualifications for career advancement. The professional nursing values of honesty, intellectualism and authority were ranked significantly higher by nurse educators than student nurses. CONCLUSIONS: The study revealed differences in self-reported general and professional values in undergraduate student nurses and nurse educators. The values of nurse educators were not always stronger than those of students. Positive relationships between particular general and professional values in both students and educators confirmed the link between professional and personal values. PMID- 28983953 TI - Alternate use of thrombopoietin receptor agonists in adult primary immune thrombocytopenia patients: A retrospective collaborative survey from Italian hematology centers. AB - Sequential use of the TPO-RAs romiplostim and eltrombopag in ITP patients failing either agent was retrospectively evaluated to assess efficacy and impact of clinical characteristics on outcome. Patients were grouped into 5 categories: efficacy issues: 1st TPO-RA failure; loss of response; non-efficacy issues: platelet fluctuations; patient's preference; adverse event development. Either one TPO-RA sequence was analyzed at 3 month and at last follow-up. 106/546 patients on TPO-RA underwent switch and 65% achieved, regained or maintained a short- term response independent of switch sequence, gender or age; lower response rates were associated with lines of previous therapy; disease duration lowers probability to respond. Clinically, patients switched for efficacy issue did not differ from those switched for non-efficacy issues. Response was achieved/regained in 57.8% of patients switched for efficacy issues, the lowest response rates were observed in non-responders to 1st TPO-RA; 80% of patients switched for non-efficacy issues maintained a response. Platelet fluctuation resolved in 44.4%. Of the 49 patients evaluable for long-term outcome, 27 were in response on therapy; 16 discontinued the TPO-RA for reasons other than efficacy, while only 6 were non responders. We confirm the efficacy of TPO-RA switch; once achieved, response to the 2nd TPO-RA seems durable. PMID- 28983954 TI - EPR monitoring of wound oxygenation as a biomarker of response to gene therapy encoding hCAP-18/LL37 peptide. AB - PURPOSE: To investigate the value of electron paramagnetic resonance oximetry to follow oxygenation in wounds treated by a plasmid-encoding host defense peptide hCAP-18/LL37. METHODS: Flaps were created on diabetic mice (7- or 12-week-old db/db mice) presenting different levels of microangiopathy. The hCAP-18/LL37 encoding plasmids were administered in wounds by electroporation. Low-frequency electron paramagnetic resonance oximetry using lithium phthalocyanine as the oxygen sensor was used to monitor wound oxygenation in flaps during the healing process. Flaps were analyzed by immunohistochemistry to assess hypoxia and cell proliferation. Kinetics of closure was also assessed in excisional skin wounds. RESULTS: A reoxygenation of the flap was observed during the healing process in the 7-week-old db/db treated mice, but not in the untreated mice and the 12-week old mice. Histological studies demonstrated less hypoxic regions and higher proportion of proliferating cells in hCAP-18/LL37-treated flaps in the 7-week-old db/db treated mice compared with untreated mice. Consistently, the kinetics of excisional wound closure was improved by hCAP-18/LL37 treatment in the 7-week-old db/db but not in the 12-week-old mice. CONCLUSIONS: Oxygenation measured by electron paramagnetic resonance oximetry is a promising biomarker of response to treatments designed to modulate wound oxygenation. Magn Reson Med 79:3267-3273, 2018. (c) 2017 International Society for Magnetic Resonance in Medicine. PMID- 28983955 TI - Associations between anti-melanoma differentiation-associated gene 5 antibody and demographics, clinical characteristics and laboratory results of patients with dermatomyositis: A systematic meta-analysis. AB - Anti-melanoma differentiation-associated gene 5 (MDA5) antibody is a specific biomarker in patients with dermatomyositis (DM). Results from several studies that examined the relationship between anti-MDA5 antibody and the demographics, clinical characteristics and laboratory results of DM patients have been conflicting. The purpose of this study was to identify the relationship, if any, of anti-MDA5 antibody with demographics, clinical characteristics and laboratory results of DM patients. PubMed, Web of Science, Embase and the Cochrane Library databases were searched for studies without language restrictions conducted before 16 March 2017. Stata version 12.0 software was used to calculate pooled odds ratios or weighted mean differences and corresponding 95% confidence intervals to determine the relationship between anti-MDA5 antibody and patient characteristics. Twenty studies comprising 1500 cases were included in this meta analysis. Anti-MDA5 antibody was strongly associated with clinically amyopathic DM (CADM) and rapidly progressive interstitial lung disease (RPILD). Anti-MDA5 antibody also increased the risk of developing eight characteristics comprising Gottron's sign or papules, mechanic's hand, V rash, skin ulcers, panniculitis, alopecia, arthritis/arthralgia and pneumomediastinum, but reduced the risk of muscle weakness, classic DM (CDM) and elevated creatine kinase (CK). Our meta analysis indicated that anti-MDA5 antibody is related to muscle weakness, Gottron's sign or papules, mechanic's hand, V rash, skin ulcers, panniculitis, alopecia, arthritis/arthralgia, pneumomediastinum, RPILD, CDM, CADM and elevated CK in patients with DM. PMID- 28983956 TI - Transitional dialysis care units: A new approach to increase home dialysis modality uptake and patient outcomes. AB - Home hemodialysis (HHD) and peritoneal dialysis (PD) are associated with better clinical outcomes, lower hospitalization rates, and improved quality of life compared with conventional in-center hemodialysis. However, <12% of patients requiring dialysis therapy use HHD or PD in the United States, even though over 90% of nephrologists would choose home-based dialysis modalities for themselves. Inadequate patient education and decision-making support are key barriers to patients choosing home-based therapy. Likewise, there are key challenges for dialysis providers, including development and optimal delivery of education materials, appropriate staffing, and training. The Satellite Healthcare Optimal Transitions (OT) Program was developed to provide education and decision support to patients during the transitional period. OT provides in-depth education in all dialysis modalities at the start of dialysis over a flexible time period (1-4 weeks, adapted for various learning curves) to allow for time to physical stabilization, self-care training, and modality choice based on each patient's individual life motivations, goals, and environments. OT may provide value to patients and providers by providing comprehensive support for dialysis modality selection, resulting in increased patient confidence to execute home dialysis with the potential for improved patient outcomes, and reduced hospitalizations. PMID- 28983957 TI - Prospective motion correction in 2D multishot MRI using EPI navigators and multislice-to-volume image registration. AB - PURPOSE: Prospective motion correction reduces artifacts in MRI by correcting for subject motion in real time, but techniques are limited for multishot 2 dimensional (2D) sequences. This study addresses this limitation by using 2D echo planar imaging (EPI) slice navigator acquisitions together with a multislice-to volume image registration. METHODS: The 2D-EPI navigators were integrated into 2D imaging sequences to allow a rapid, real-time motion correction based on the registration of three navigator slices to a reference volume. A dedicated slice iteration scheme was used to limit mutual spin-saturation effects between navigator and image data. The method was evaluated using T2 -weighted spin echo and multishot rapid acquisition with relaxation enhancement (RARE) sequences, and its motion-correction capabilities were compared with those of periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER). Validation was performed in vivo using a well-defined motion protocol. RESULTS: Data acquired during subject motion showed residual motion parameters within +/ 0.5 mm and +/-0.5 degrees , and demonstrated a substantial improvement in image quality compared with uncorrected scans. In a comparison to PROPELLER, the proposed technique preserved a higher level of anatomical detail in the presence of subject motion. CONCLUSIONS: EPI-navigator-based prospective motion correction using multislice-to-volume image registration can substantially reduce image artifacts, while minimizing spin-saturation effects. The method can be adapted for use in other 2D MRI sequences and promises to improve image quality in routine clinical examinations. Magn Reson Med 78:2127-2135, 2017. (c) 2017 International Society for Magnetic Resonance in Medicine. PMID- 28983958 TI - Management of syphilis in pregnancy: Knowledge and practices of health care providers and barriers to the control of disease in Teresina, Brazil. AB - AIMS: The aim of the study is to verify the knowledge and practices of health professionals working in prenatal care (PNC) related with syphilis during pregnancy and to identify the main barriers to the implementation of protocols for the control of this disease. METHODS: A cross-sectional study in Teresina, Brazil, from January to May 2015, was conducted with 366 physicians and nurses working in PNC, corresponding to 70% of eligible professionals. We evaluated 20 knowledge and practice criteria related to the diagnosis and treatment of syphilis during pregnancy with a 95% compliance standard. We performed descriptive analysis of the data and used chi2 statistical test to verify differences according to professional category. RESULTS: Only 2 criteria, "knowledge about mother to child transmission according to gestational age" and "counselling on infection," reached 95% compliance. Knowledge of the epidemiological profile of congenital syphilis and the goal of elimination of congenital syphilis and knowledge about serological tests had scores below 50%, while practices related with posttest counselling, cure control, and treatment of partners reached 60%. We identified organisational barriers related to the late initiation of PNC, to the delayed return of syphilis test results, to the application of benzathine penicillin in primary care units and to the treatment of partners. CONCLUSIONS: Strategies for early initiation of PNC, implementation of rapid tests for syphilis, ensuring treatment of pregnant women with penicillin, adequate partner treatment, and continued education of health professionals on clinical management and counselling in sexually transmitted diseases are necessary to eliminate congenital syphilis. PMID- 28983959 TI - Countywide implementation of crisis intervention teams: Multiple methods, measures and sustained outcomes. AB - The crisis intervention team (CIT) is a tool that can be used to foster pre booking diversion of individuals with mental illness from the criminal justice system and into community treatment services. Although CIT is often implemented solely as the training of law enforcement officers, the model stipulates that CIT is a vehicle for collaboration with community stakeholders who share a similar philosophy, as well as expanded mental health services offering a 24 hour-seven days per week drop-off option for law enforcement officers. This case study presents the countywide implementation of CIT and expands previous findings on the prevalence of officer interaction with persons with mental health issues and CIT training outcomes, including changes in officer perception of individuals with mental health issues. Furthermore, analysis of the disposition of calls for officer assistance coded as mental health or suicide found significant increases in officer drop-offs to the mental health crisis center post-CIT training. Interrupted time series analysis determined that this change has been sustained over time, perhaps owing to the unique communication between county law enforcement and mental health staff. Implications for policy and practice are discussed. PMID- 28983961 TI - Developing a predictive model for fine particulate matter concentrations in low socio-economic households in Durban, South Africa. AB - In low-resource settings, there is a need to develop models that can address contributions of household and outdoor sources to population exposures. The aim of the study was to model indoor PM2.5 using household characteristics, activities, and outdoor sources. Households belonging to participants in the Mother and Child in the Environment (MACE) birth cohort, in Durban, South Africa, were randomly selected. A structured walk-through identified variables likely to generate PM2.5 . MiniVol samplers were used to monitor PM2.5 for a period of 24 hours, followed by a post-activity questionnaire. Factor analysis was used as a variable reduction tool. Levels of PM2.5 in the south were higher than in the north of the city (P < .05); crowding and dwelling type, household emissions (incense, candles, cooking), and household smoking practices were factors associated with an increase in PM2.5 levels (P < .05), while room magnitude and natural ventilation factors were associated with a decrease in the PM2.5 levels (P < .05). A reasonably robust PM2.5 predictive model was obtained with model R2 of 50%. Recognizing the challenges in characterizing exposure in environmental epidemiological studies, particularly in resource-constrained settings, modeling provides an opportunity to reasonably estimate indoor pollutant levels in unmeasured homes. PMID- 28983960 TI - Thermal limits on MV x-ray production by bremsstrahlung targets in the context of novel linear accelerators. AB - PURPOSE: To study the impact of target geometrical and linac operational parameters, such as target material and thickness, electron beam size, repetition rate, and mean current on the ability of the radiotherapy treatment head to deliver high-dose-rate x-ray irradiation in the context of novel linear accelerators capable of higher repetition rates/duty cycle than conventional clinical linacs. METHODS: The depth dose in a water phantom without a flattening filter and heat deposition in an x-ray target by 10 MeV pulsed electron beams were calculated using the Monte-Carlo code MCNPX, and the transient temperature behavior of the target was simulated by ANSYS. Several parameters that affect both the dose distribution and temperature behavior were investigated. The target was tungsten with a thickness ranging from 0 to 3 mm and a copper heat remover layer. An electron beam with full width at half maximum (FWHM) between 0 and3 mm and mean current of 0.05-2 mA was used as the primary beam at repetition rates of 100, 200, 400, and 800 Hz. RESULTS: For a 10 MeV electron beam with FWHM of 1 mm, pulse length of 5 MUs, by using a thin tungsten target with thickness of 0.2 mm instead of 1 mm, and by employing a high repetition rate of 800 Hz instead of 100 Hz, the maximum dose rate delivered can increase two times from 0.57 to 1.16 Gy/s. In this simple model, the limiting factor on dose rate is the copper heat remover's softening temperature, which was considered to be 500 degrees C in our study. CONCLUSIONS: A high dose rate can be obtained by employing thin targets together with high repetition rate electron beams enabled by novel linac designs, whereas the benefit of thin targets is marginal at conventional repetition rates. Next generation linacs used to increase dose rate need different target designs compared to conventional linacs. PMID- 28983962 TI - Etiology of developmental spinal stenosis: A genome-wide association study. AB - Our study aimed to identify possible single nucleotide polymorphisms (SNPs) via a genome-wide association study (GWAS) approach and a candidate gene platform that were associated with lumbar developmental spinal stenosis (DSS). Southern Chinese population-based study volunteers were assessed (age range: 18-55 years). DSS was defined as the anteroposterior bony spinal canal diameter on T1-weighted axial MRI of L1 to S1. Genotyping was performed using the Illumina HumanOmniZhongHua-8 BeadChip. Using the canal diameter as the quantitative trait, genomic statistical analyses was performed. A total of 469 subjects were recruited. The mean axial AP measurements noted were: L1: 21.8 mm, L2: 21.9 mm, L3: 22.4 mm, L4: 20.2 mm, L5: 19.6 mm, and S1: 17.3 mm. Q-Q plots of genome-wide associations found significant differences in L4 and L5 measurements. More significant SNPs were found on chromosomes 8, 11, and 18. Low-density lipoprotein receptor-related protein 5 on chromosome 11 was found to be an important functional gene in canal bony development via candidate gene approach. We found two clusters in the findings with one including the upper levels (L1-L4) and the other the lower levels (L5 and S1). This is the first GWAS addressing DSS. The presence of multiple SNPs suggests a multi-factorial origin of DSS. Further analyses noted region-specific genetic predisposition, delineating distinct upper to lower lumbar regions of DSS. With better understanding of the DSS phenotype and genetic markers, the at risk population can be identified early, preventative measures can be initiated, lifestyle/activity modification can be implemented, and more novel and precision based therapeutics can be developed. (c) 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1262-1268, 2018. PMID- 28983963 TI - Beyond rescue: Implementation and evaluation of revised naloxone training for law enforcement officers. AB - OBJECTIVE: This study describes the implementation and evaluation of revised opioid overdose prevention and education of naloxone training for law enforcement officers (LEOs) that added: (1) a recovery testimony and (2) the process for deputy-initiated referrals postnaloxone administration. DESIGN AND SAMPLE: Evaluation regarding the naloxone training included a pre- and postopioid overdose knowledge surveys (N = 114) and subsequent 1-year postnaloxone training outcomes. RESULTS: Pre- and posttest scores for all knowledge outcome measures were statistically significant (p < .001) with favorable comments pertaining to the recovery testimony. Out of 31 individuals who received naloxone, 6 individuals (19.4%) continue to be in treatment or received some treatment services. The most common symptoms reported were unconsciousness/unresponsiveness (40.5%), abnormal breathing patterns (24.3%), and blue lips (16.2%). The majority of the calls (65.6%) were to a residential area, and the time for naloxone revival ranged <1-10 min (M = 3.48; SD = 2.27). CONCLUSION: As nearly 20% of individuals sought treatment after a LEO-initiated referral, it is recommended that other agencies consider the referral process into the training. Future research will investigate the impact of the recovery testimony in reducing the stigma of addiction. PMID- 28983965 TI - Unusual post-patch testing erythema: a late, granulomatous, non-eczematous reaction to gold sodium thiosulphate. PMID- 28983964 TI - Dopamine cross-reacts with adrenoreceptors in cortical astrocytes to induce BDNF expression, CREB signaling and morphological transformation. AB - Expression of brain-derived neurotrophic factor (BDNF) is induced in cultured rat cortical astrocytes by catecholamines norepinephrine and dopamine as well as selective alpha1 and beta adrenergic agonists. However, it has remained unknown which receptors mediate dopamine-induced BDNF upregulation in astrocytes. Here, we demonstrate that beta adrenoreceptors are the main mediators of this effect in cultured cortical astrocytes, while alpha1 adrenoreceptors and D1 dopamine receptors contribute to a lesser extent. We show that in cortical astrocytes BDNF exon IV and exon VI containing mRNAs are induced by dopamine and norepinephrine via CREB-dependent signaling and that this regulation is mediated by a mechanism that is distinct from activity-dependent CREB-mediated activation of BDNF transcription in neurons. We also show that regulation of BDNF promoters IV and VI by catecholamines requires a distal regulatory element in the BDNF locus. Finally, we demonstrate that dopamine-induced astrocyte stellation and induction of CREB signaling are mediated by cross-reaction of dopamine with beta adrenoreceptors. PMID- 28983966 TI - Joint water-fat separation and deblurring for spiral imaging. AB - PURPOSE: Most previous approaches to spiral Dixon water-fat imaging perform the water-fat separation and deblurring sequentially based on the assumption that the phase accumulation and blurring as a result of off-resonance are separable. This condition can easily be violated in regions where the B0 inhomogeneity varies rapidly. The goal of this work is to present a novel joint water-fat separation and deblurring method for spiral imaging. METHODS: The proposed approach is based on a more accurate signal model that takes into account the phase accumulation and blurring simultaneously. A conjugate gradient method is used in the image domain to reconstruct the deblurred water and fat iteratively. Spatially varying convolutions with a local convergence criterion are used to reduce the computational demand. RESULTS: Both simulation and high-resolution brain imaging have demonstrated that the proposed joint method consistently improves the quality of reconstructed water and fat images compared with the sequential approach, especially in regions where the field inhomogeneity changes rapidly in space. The loss of signal-to-noise-ratio as a result of deblurring is minor at optimal echo times. CONCLUSIONS: High-quality water-fat spiral imaging can be achieved with the proposed joint approach, provided that an accurate field map of B0 inhomogeneity is available. Magn Reson Med 79:3218-3228, 2018. (c) 2017 International Society for Magnetic Resonance in Medicine. PMID- 28983967 TI - Case of engraftment syndrome appearing as scratch dermatitis. PMID- 28983968 TI - Individualized 6-mercaptopurine increments in consolidation treatment of childhood acute lymphoblastic leukemia: A NOPHO randomized controlled trial. AB - OBJECTIVES: This randomized controlled trial tested the hypothesis that children with non-high-risk acute lymphoblastic leukemia could benefit from individualized 6-mercaptopurine increments during consolidation therapy (NCT00816049). Primary and secondary end points were end of consolidation minimal residual disease (MRD) positivity and event-free survival. METHODS: 392 patients were randomized to experimental and 396 to standard therapy. Patients allocated to standard therapy received oral 6-mercaptopurine (25 mg/m2 /day) from days 30 to 85, while the experimental arm received stepwise increments of additional 25 mg/m2 /day beginning on days 50 and/or 71 unless dose-limiting myelosuppression had occurred. RESULTS: In the experimental arm, 166 patients (42%) received one dose increment, and 62 (16%) received two. Fifty-seven of 387 (15%) patients in the experimental arm were MRD positive at end of consolidation vs 77 of 389 (20%) in the control arm (P = .08). Five-year probability of event-free survival was 0.89 (95% CI: 0.85-0.93) in the experimental arm vs 0.93 (0.90-0.96) in the control arm (P = .13). The median accumulated length of 6-mercaptopurine treatment interruptions was 7 (IQR 2-12) in the experimental arm vs 4 (IQR 0-10) in the control arm (P = .002). CONCLUSION: This study found no benefit from individualized 6-mercaptopurine increments compared to standard therapy. PMID- 28983969 TI - A high-performance gradient insert for rapid and short-T2 imaging at full duty cycle. AB - PURPOSE: The goal of this study was to devise a gradient system for MRI in humans that reconciles cutting-edge gradient strength with rapid switching and brings up the duty cycle to 100% at full continuous amplitude. Aiming to advance neuroimaging and short-T2 techniques, the hardware design focused on the head and the extremities as target anatomies. METHODS: A boundary element method with minimization of power dissipation and stored magnetic energy was used to design anatomy-targeted gradient coils with maximally relaxed geometry constraints. The design relies on hollow conductors for high-performance cooling and split coils to enable dual-mode gradient amplifier operation. With this approach, strength and slew rate specifications of either 100 mT/m with 1200 mT/m/ms or 200 mT/m with 600 mT/m/ms were reached at 100% duty cycle, assuming a standard gradient amplifier and cooling unit. RESULTS: After manufacturing, the specified values for maximum gradient strength, maximum switching rate, and field geometry were verified experimentally. In temperature measurements, maximum local values of 63 degrees C were observed, confirming that the device can be operated continuously at full amplitude. Testing for peripheral nerve stimulation showed nearly unrestricted applicability in humans at full gradient performance. In measurements of acoustic noise, a maximum average sound pressure level of 132 dB(A) was determined. In vivo capability was demonstrated by head and knee imaging. Full gradient performance was employed with echo planar and zero echo time readouts. CONCLUSION: Combining extreme gradient strength and switching speed without duty cycle limitations, the described system offers unprecedented options for rapid and short-T2 imaging. Magn Reson Med 79:3256-3266, 2018. (c) 2017 International Society for Magnetic Resonance in Medicine. PMID- 28983970 TI - Increasing incidence of primary central nervous system lymphoma but no improvement in survival in Sweden 2000-2013. AB - OBJECTIVES: This study aims to characterize the epidemiology of immunocompetent Primary central nervous system lymphoma (PCNSL) diagnosed 2000-2013 in Sweden. METHODS: Cases were identified in the population-based Swedish Lymphoma Register. Incidence per 100 000 person-years and 95% confidence intervals (CI) were calculated, and PCNSL-specific survival was estimated using relative survival. Tests for temporal trends were performed using Poisson regression. Population incidence of all brain tumors was retrieved for comparison. RESULTS: With 359 identified PCNSL cases (median age 66 years), overall incidence was 0.26 (95% CI: 0.24-0.29) and the average annual increase 4% (P = .002). The increasing trend was primarily observed among elderly individuals (70+ years). Similarly, an increase in incidence of all brain tumors was noted only among the elderly. There was no significant improvement in relative survival across the study period although, among fit patients (with Eastern Cooperative Oncology Group, EGOC 0), survival plateaued 6 years after diagnosis. CONCLUSION: The increasing PCNSL incidence in the elderly was consistent with an increasing incidence of brain tumors of any type and may in part be attributable to improved diagnostics and reporting in this group. New treatment options have not yet translated into general survival improvements in a population-based setting, although the presence of long-term survivors among fit patients is encouraging. PMID- 28983971 TI - Effects of caffeinated alcoholic beverages with low alcohol and high caffeine content on cognitive and motor functions. AB - OBJECTIVE: In Taiwan, caffeinated alcoholic beverages (CABs), with high caffeine but low alcohol concentrations compared to those sold in Western countries, are commonly consumed at work and have been associated with work-related injuries. However, the effects on cognitive and motor functions and self-perception have not been examined. METHODS: Twenty-eight healthy male volunteers (mean age: 32.6 +/- 2.7) participated in the study. Each participant visited our laboratory 4 times at intervals of at least 1 week and was assigned to one of 4 trials in a counterbalanced order at each visit: placebo, alcohol, caffeinated energy drink, and CAB. They completed the subjective perception ratings, go/no-go tasks, Stroop color-word tests, Purdue pegboard tests, and the standardized field sobriety test. We used analysis of variance to examine the intraindividual differences in the performance. RESULTS: Consuming alcohol of 0.23 g/kg typically consumed by Taiwanese CAB drinkers caused significant impairments in fine and crude motor functions; caffeine (1.5 mg/kg) did not antagonize these effects but led to an improvement in response speed in the go/no-go task. The subjective perceptions produced by alcohol were not masked by caffeine. CONCLUSIONS: CABs that contains a higher ratio of caffeine to alcohol did not counteract the motor function impairments induced by alcohol. PMID- 28983972 TI - On the composition of gastroliths from broiler breeders. AB - The purpose of this study was to ascertain the composition and origin of certain gastroliths or gizzard stones from broiler breeders (Gallus gallus domesticus). Fourier transform infrared spectroscopy (FTIR) and X-ray powder diffraction techniques were used as analysis tools. The main components resulted to be organic fibre and minerals referred to a pegmatite rock (quartz, feldspar albite and haematite) used as grit. Although the generally accepted purpose of gastroliths in chicken is the crushing and grinding of foodstuff in the ventriculus, the importance of mineral uptake from grit of iron and other essential elements such as Al, Ca, K, Cl, P, Ti, Mn, Mg, Cu, Zn and Zr (in ppm) as a secondary effect of the abrasion and dissolution of gastroliths should not be disregarded. PMID- 28983973 TI - Granuloma annulare associated with immune checkpoint inhibitors. PMID- 28983974 TI - Molecular design of Stat3-derived peptide selectivity between BET proteins Brd2 and Brd4 in ovarian cancer. AB - Stat3 signaling has been recognized as a potential therapeutic target of human ovarian cancer. The signaling is transducted through the peptide-medicated interaction of Stat3 with BET family members Brd2 and Brd4 -- 2 highly homologous proteins involved in differential downstream pathways. Here, we reported a successful design of peptide selectivity between the Brd2 and Brd4. The design resulted in 3 linear peptides SMSLQCXYLGVA, QSKVLTXSYWGA, and RQCNLGXLYMNY with high or moderate selectivity for Brd2 over Brd4 (S = 3.3-fold, 6.8-fold, and 4.2 fold, respectively) as compared with the native Stat3 peptide 281 HNLLRIXQFLQS292 (S = 2.5-fold). Structural analysis revealed that peptide N-terminus and hydrogen bonds play important roles in the peptide interaction stability and specificity with Brd2 and Brd4. This study would help to establish an integrated in silico-in vitro method for rational molecular design of peptide ligand selectivity between homologous protein receptors. PMID- 28983975 TI - Hyperglycaemia in transition dairy cows: Effects of lactational stage and conjugated linoleic acid supplementation on glucose metabolism and turnover. AB - Supplementing conjugated linoleic acid (CLA) is supposed to spare glucose due to the milk fat-depressing effect of the trans-10, cis-12 CLA isomer, and allows repartitioning nutrients despite an energy deficiency in early lactation. However, there is still a lack of knowledge in terms of the dynamic pattern of the glucose turnover in transition dairy cows. We hypothesized that dairy cows supplemented with CLA have an altered rate of glucose turnover and insulin sensitivity during early lactation. We conducted three consecutive hyperglycaemic clamps (HGC) in weeks -2, +2 and +4 relative to parturition in Holstein cows supplemented daily either with 70 g of lipid-encapsulated CLA (6.8 g trans-10, cis-12 and 6.6 g of the cis-9, trans-11 CLA isomer; CLA; n = 11) or with 56 g of control fat (CON; n = 11). From week -3 up to week +4 relative to parturition, milk yield and dry matter intake (DMI) were recorded daily, while body weight (BW) and milk composition were obtained once weekly. Blood samples were taken once weekly and every 30 min during the HGC. Plasma was analysed for concentrations of glucose, fatty acids (FFA), beta-hydroxybutyrate (BHB), insulin, triglycerides and cholesterol. The CLA supplementation did not affect performance and metabolic parameters except for BHB and cholesterol. Furthermore, insulin concentrations and insulin sensitivity were affected by treatment. During the HGC in early lactation, insulin response was lower and decrease in FFA and BHB greater compared with the HGC in week -2 although glucose target concentration achieved during the steady-state period was similar for all three HGC. Our findings in terms of insulin and cholesterol suggest that body reserves are preserved through CLA feeding without restraining animal's performance. Furthermore, CLA effects on cholesterol and triglyceride concentrations indicated beneficial effects on hepatic lipid export contributing to an improved efficiency of prevailing metabolites in circulation. PMID- 28983976 TI - An unresponsive progressive pustular and crusting dermatitis with acantholysis in nine cats. AB - BACKGROUND: Between 2000 and 2012, nine cats were examined with a visually distinctive, progressive crusting dermatitis that was poorly responsive to all attempted therapies. OBJECTIVES: Documentation of clinical and histopathological findings of this disease. ANIMALS: Nine privately owned cats. METHODS: Retrospective study. RESULTS: Eight neutered males and one (presumably spayed) female ranging in age from two to eight years, presented for a progressive, well demarcated, crusting dermatitis with variable pruritus of 1.5 months to five years duration. All cats lived in northern California, USA; seven lived within a 30 mile radius. Two males were littermates. Histopathological investigation showed both parakeratotic and orthokeratotic crusts, intraepidermal pustules and superficial folliculitis with rare to frequent acantholytic cells. Bacterial and fungal cultures were performed in six cats: meticillin-susceptible Staphylococcus pseudintermedius was isolated in three cats, two colonies of Trichophyton terrestre and three of Malassezia pachydermatis were isolated from one cat each. Treatment with various antibiotics, antifungal and a variety of immunosuppressive medications did not alter the progressive nature of the skin disease. CONCLUSIONS AND CLINICAL IMPORTANCE: The described disease shares some clinical and histopathological features with pemphigus foliaceus, but the lack of response to treatment, its progressive nature and the possible relatedness of some of the cats set it apart. The aetiology of this acantholytic dermatitis remains unknown. PMID- 28983977 TI - Quality of Dutch dermatological guidelines according to AGREE II. PMID- 28983978 TI - Painful interdigital lesion: could it be syphilis? PMID- 28983979 TI - Effect of marine by-product meals on hen egg production parameters, yolk lipid composition and sensory quality. AB - The effect of including 5% marine by-product meals in feeds of laying hens on egg production, composition and sensory characteristics was tested. Marine by-product meals were prepared using two methods: (i) cooking (100 degrees C/10 min) followed by drying (60 degrees C/24 hr) or (ii) grinding followed by drying. The raw materials used for meal production were scallop or squid viscera, shrimp heads or whole mackerel. A total of 108 laying hens were allocated to nine diet treatments; one control diet (corn and soya bean based) and eight experimental diets, containing 95% of the control feed and 5% of the experimental meal for three weeks. Daily intake was higher in hens fed the dried mackerel and cooked shrimp meals. All the experimental treatments showed significantly higher concentration of n-3 HUFA in yolk reserves and phospholipids compared to the control (0.12-0.13 g per 100 g), especially those with scallop or squid prepared by both methods (0.53-0.95 g per 100 g). Scallop, squid and shrimp meal inclusion in the feed produced eggs with more astaxanthin (0.22 mg per 100 g) while this carotenoid was absent in the control and mackerel treatments. Visual evaluation of raw yolk colour increased with the inclusion of marine by-product meals with higher values in hens fed shrimp heads (13), followed by scallop viscera (11), squid viscera (9), and with similar values for mackerel and control (4). The taste, aroma, texture and colour of cooked eggs from different treatments were not statically different when evaluated by a panel of 60 untrained people. These results suggest that meals from marine by-products are a better alternative for improving egg yolk composition by increasing n-3 HUFA when compared to fishmeal as they also increase astaxanthin and yolk pigmentation without affecting egg sensory characteristics. PMID- 28983980 TI - Three cases of facial erythema with dryness and pruritus in psoriasis patients during treatment with IL-17 inhibitors. PMID- 28983981 TI - Neurocognitive performances of visuospatial attention and the correlations with metabolic and inflammatory biomarkers in adults with obesity. AB - NEW FINDINGS: What is the central question of this study? Obesity is linked to cognitive deficits, elevated energy metabolic indices and low-grade systemic inflammation. Do the relationships between neurocognitive performance and the biochemical markers (e.g. energy metabolic indices and inflammatory cytokines) occur independently of factors known to be associated with neurocognitive dysfunction (i.e. cardiorespiratory fitness) in young adults? What is the main finding and its importance? Young obese adults showed poorer neuropsychological performances, aberrant neural activity and higher C-reactive protein and energy metabolic indices. The higher leptin and C-reactive protein concentrations showed a significant negative association with lower P3 amplitudes. However, leptin was the sole predictive factor, implicating hyperleptinaemia in the altered neurocognitive function observed in obesity. The present study was designed to explore the neurophysiological mechanism of visuospatial attention deficits in obese adults and to examine the relationships between neurocognitive (neuropsychological and neurophysiological) performances and the biochemical markers. Thirty obese adults and 30 healthy-weight control subjects, categorized by body mass index and percentage fat as measured with dual-energy X-ray absorptiometry, provided a fasting blood sample and performed a visuospatial attention protocol with concomitant electrophysiological recording. The obese group showed slower reaction times and smaller P3 amplitudes when performing the cognitive task. Even when controlling for the covariable of cardiorespiratory fitness, the results remained. In addition, the serum concentrations of insulin, glucose, leptin and C-reactive protein were significantly higher in the obese group relative to the control group, but not those of interleukin-6, interleukin 1beta and tumour necrosis factor-alpha. Partial correlations adjusting for cardiorespiratory fitness showed that leptin and C-reactive protein concentrations in the obese group were negatively associated with poorer neurophysiological (i.e. P3 amplitude) performance. However, the regression analysis showed that leptin was the sole predictor of P3 amplitude in the obese group. These findings indicate that the individuals with obesity exhibited neurocognitive deficits when performing the visuospatial attention task, and serum leptin concentrations could be one of the influential factors. PMID- 28983982 TI - Investigation of the correlation of serum IL-31 with severity of dermatitis in an experimental model of canine atopic dermatitis using beagle dogs. AB - BACKGROUND: IL-31 is a cytokine that is believed to play an important role in atopic dermatitis (AD). IL-31 levels positively correlate with disease severity in children with AD. Currently, there is no study that has investigated such a correlation in atopic dogs. HYPOTHESIS/OBJECTIVE: The purpose of this study was to evaluate the correlation between IL-31 serum levels and severity of dermatitis. It was hypothesized that a positive correlation exists between severity of AD and circulating levels of IL-31. ANIMALS: Sixteen atopic beagles experimentally sensitized to house dust mites. METHODS: Atopic beagles were exposed to dust mites epicutaneously twice weekly for four weeks. Severity of dermatitis was scored by the Canine Atopic Dermatitis and Extent Severity Index, 3rd iteration (CADESI-03) on days 0 and 28. Blood samples were taken on days 0 and 28 to measure serum IL-31 using a commercially available ELISA. RESULTS: Correlation between CADESI-03 scores and serum IL-31 levels was not detected on day 0 (Pearson, r = -0.2609, P = 0.3291). After flare-up of dermatitis was induced with allergen exposure, a significant positive correlation was detected between serum IL-31 and CADESI-03 on Day 28 (r = 0.6738, P = 0.004). CONCLUSIONS AND CLINICAL IMPORTANCE: Positive correlation was detected in active disease between severity of dermatitis and circulating levels of IL-31. Additional studies are needed to investigate this correlation in other breeds of dogs and to test whether circulating levels of IL-31 may predict clinical response to biological agents aimed at IL-31. PMID- 28983983 TI - Flavonoid Constituents of Phlomis (Lamiaceae) Species Using Liquid Chromatography Mass Spectrometry. AB - INTRODUCTION: Phlomis is one of the medicinal genera of Lamiaceae. This genus has unique medicinal properties. Consequently, appropriate methods need to be described for the identification of the chemical compounds. OBJECTIVE: A liquid chromatography tandem mass spectrometry (LC-MS/MS) technique on a triple quadrupole mass spectrometer (TQMS) was used for separation and identification of leaf flavonoid compounds for seven Phlomis species including Phlomis kurdia, Ph. aucheri, Ph. olivieri, Ph. bruguieri, Ph. persica, Ph. anisodonta and Ph. elliptica. METHODOLOGY: The flavonoid solution of air-dried leaves (10.5 g) was extracted using 85% methanol. The chromatogram was treated with three systems: methanol-water, chloroform-methanol and acetic acid. The extracts were analysed using LC-MS/MS. The MS2 detection was performed under negative mode electrospray ionisation (ESI). The identification of constituents was based on authentic references used in the identification process. RESULTS: A total of 35 chemical compounds were detected from which 32 were identified as flavonoids through comparison with published literature and reference standards. These compounds were distributed in four flavonoid classes. Flavones (12), flavonols (11), flavanones (8) and flavane (1) were the main groups appearing in almost all of the studied samples. The flavonoids such as naringenin, chrysoeriol, eriodictyol, dimethoxyflavanone, apigenin, luteolin, kaempferol and rhamnetin were in high proportions. Moreover, 22 flavonoid compounds were first reported in this study for Phlomis species. CONCLUSION: The fragmentation patterns of the compounds during collision induced dissociation (CID) clarified information of the compounds analysed. The detailed flavonoid compositions of Phlomis species provide the appropriate context from phytochemical and phytotherapeutics points of view. Copyright (c) 2017 John Wiley & Sons, Ltd. PMID- 28983984 TI - Predictors of aging based on the analysis of heart rate variability. AB - BACKGROUND: The current significant progress in the use of heart rate variability in the solution of many diagnostic and therapeutic problems is determined by the availability of standardized methods of measurement and physiological interpretation of heart rate variability indices on the one hand and the high technological level of state-of-the-art electronic measuring equipment that is used for automatic registration and computer processing of cardio-signals. METHODS: A retrospective analysis of anonymized cardio screening results of 22,433 adult residents of 565 settlements (cities and villages) across all 20 administrative districts of the Khmelnytskyi Region (Ukraine) was conducted to find a statistically significant connection between individual heart rate variability parameters and the age of people. RESULTS: Primary statistical analysis and visualization showed a correlation between the selected heart rate variability parameters and the age and sex of the examined persons. The study found values of the predicted age slightly over estimation versus the actual age for very young test subjects and below estimation for elderly subjects. CONCLUSION: The use of neural network computations and the modification of the algorithm through the construction of individual training samples for different age intervals, and the creation of individual ensembles of classification neural networks, therefore achieved a prediction of the age of examined persons based on the values of their time and frequency domain heart rate variability indices, with 87% accuracy for women and 85% accuracy for men in the 66-85 years age interval and at least 85% for age groups across the entire sample. PMID- 28983986 TI - Effects of animal type (wild vs. domestic) and diet alfalfa level on intake and digestibility of European adult rabbits (Oryctolagus cuniculus). AB - The aim of this study was to evaluate the effect of the level of alfalfa in the diet on feed intake and digestibility of two types of rabbits, wild (Oryctolagus cuniculus algirus) vs. domestic (O. cuniculus cuniculus). Ten wild (W; mean LW = 927 g) and 10 domestic (D; mean LW = 4,645 g) adult rabbit does were fed ad libitum two pelleted diets: a control diet (C) with 15% of dehydrated alfalfa hay (as feed basis) and a test diet (A) with 36% of dehydrated alfalfa hay (as feed basis), according to a change-over design. Wild does dry matter (DM) intake per kg live weight (BW) was 55% higher (p < .001) than the intake of the D ones (58 g vs. 37 g DM per kg BW respectively). However, no difference (p > .05) was found when intake was expressed per kg0.75 BW (ca. 56 g DM) and tended to be higher (p = .07) in D does when expressed per kg0.67 BW (62 g vs. 55 g DM). Domestic does showed a higher (p < .05) DM, organic matter, crude energy and neutral detergent fibre digestibility (3; 2; 3; 3 percentage points respectively) than W does. The amount of nutrients and energy digested by D does was lower per kg BW (p < .001), similar per kg0.75 BW (p > .05) and tended to be higher per kg0.67 BW (p < .1) than in W does. The diet content of alfalfa did not affect (p > .05) the feed intake nor the diet digestibility. This study suggests that W rabbits exhibit a higher intake per kg BW and a lower digestibility than their D counterparts, which results in similar digestible nutrient and energy intake per kg BW powered to 0.75. The nutritive value of dehydrated alfalfa for rabbits, evaluated through intake and digestibility, seems to be equivalent to their base diets (forage plus concentrate). PMID- 28983987 TI - Novel PNPLA1 mutations in two Italian siblings with autosomal recessive congenital ichthyosis. PMID- 28983985 TI - ZENK induction in the zebra finch brain by song: Relationship to hemisphere, rhythm, oestradiol and sex. AB - Oestradiol is abundant in the zebra finch auditory forebrain and has the capacity to modulate neural responses to auditory stimuli with specificity as a result of both hemisphere and sex. Arrhythmic song induces greater ZENK expression than rhythmic song in the caudomedial nidopallium (NCM), caudomedial mesopallium (CMM) and nucleus taeniae (Tn) of adult zebra finches. The increases in the auditory regions (i.e. NCM and CMM) may result from detection of errors in the arrhythmic song relative to the learned template. In the present study, zebra finches were treated with oestradiol, the aromatase inhibitor fadrozole or a control and then exposed to rhythmic or arrhythmic song to assess the effect of oestradiol availability on neural responses to auditory rhythms. ZENK mRNA was significantly greater in the left hemisphere within the NCM, CMM and Tn. Main effects of sex were detected in both auditory regions, with increased ZENK in males in the NCM and in females in the CMM. In the CMM, an effect of hormone treatment also existed. Although no pairwise comparison was statistically significant, the pattern suggested greater ZENK expression in control compared to both fadrozole- and oestradiol-treated birds. In the NCM, an interaction between sex and hormone treatment suggested that the sex effect was restricted to control animals. An additional interaction in the NCM among sex, stimulus rhythmicity and hemisphere indicated that the strongest effect of laterality was present in males exposed to arrhythmic song. The hormone effects suggest that an optimal level of oestradiol may exist for processing rhythmicity of auditory stimuli. The overall pattern for left lateralisation parallels the left lateralisation of language processing in humans and may suggest that this hemisphere is specialised for processing conspecific vocalisations. The reversed sex differences in the NCM and CMM suggest that males and females differentially rely on components of the auditory forebrain for processing conspecific song. PMID- 28983988 TI - Clinical outcome and prognosis of dogs with histopathological features consistent with epitheliotropic lymphoma: a retrospective study of 148 cases (2003-2015). AB - BACKGROUND: Limited information is available regarding the treatment and outcome of dogs with epitheliotropic lymphoma. The disease typically has a poor prognosis. OBJECTIVES: To characterize the clinical signs, identify prognostic factors and evaluate the treatment outcome of dogs with epitheliotropic lymphoma. METHODS: A retrospective review of medical records from 2003 to 2015. Treatment details, tumour response and survival time were recorded for 148 dogs. Potential prognostic factors were evaluated for their statistical effect on median survival time. RESULTS: The overall median survival time for dogs was 264 days (cutaneous: 130 days; mucocutaneous/mucosal: 491 days). On multivariate analysis, a shorter median survival time was associated with the cutaneous form (P < 0.001) and the presence of multiple lesions (P < 0.001). Among 80 dogs with cutaneous lesions, chemotherapy treatment (P < 0.001) and having a solitary lesion (P < 0.001) were associated with longer median survival. In 72 dogs with multiple cutaneous lesions, chemotherapy intervention (P < 0.001), retinoid treatment (P = 0.001) and complete remission (P = 0.001) were associated with longer median survival. In 68 dogs with mucocutaneous/mucosal lesions, decreasing age (P = 0.020) and a solitary lesion (P = 0.015) were associated with longer median survival. CONCLUSION: Canine epitheliotropic lymphoma may be divided into cutaneous and mucocutaneous/mucosal forms. Solitary lesions have a better prognosis. Dogs with multiple lesions appear to benefit from chemotherapy and retinoid treatment, with those attaining complete remission having longer survival times. Multi-agent chemotherapy could be considered in dogs with cutaneous lesions that fail to respond to single-agent chemotherapy. PMID- 28983989 TI - Detailed positron annihilation lifetime spectroscopic investigation of atrazine imprinted polymers grafted onto PE/PP non-woven fabrics. AB - This study presents the preparation of molecularly imprinted matrices by using radiation-induced grafting technique onto polyethylene/polypropylene (PE/PP) non woven fabrics. Atrazine imprinted polymers were grafted onto PE/PP non-woven fabrics through the use of methacrylic acid (MAA) and ethylene glycol dimethylacrylate (EGDMA) as the functional monomer and crosslinking agent, respectively. Grafted MIPs were characterized by attenuated total reflectance Fourier transform infra-red spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), elemental analysis, scanning electron microscopy (SEM), and positron annihilation lifetime spectroscopy (PALS). The average diameter of free volume holes was determined as 0.612 nm which correlates very well with the size of template molecule atrazine, 0.512 nm. Binding behaviors were investigated against various factors, such as concentration of template molecule, pH, and contact time. Furthermore, the specific selectivity of grafted MIP on non-woven fabric was studied by using other common triazine compounds, such as simazine and metribuzine which show structural similarities to atrazine. The specific binding values for atrazine, simazine, and metribuzine were determined as 40%, 2.5%, and 1.5%, respectively. PMID- 28983990 TI - Migration dermatology: an issue to consider? PMID- 28983991 TI - Neonatal overfeeding by small-litter rearing sensitises hippocampal microglial responses to immune challenge: Reversal with neonatal repeated injections of saline or minocycline. AB - The early-life period is extremely vulnerable to programming effects from the environment, many of which persist into adulthood. We have previously demonstrated that adult rats overfed as neonates have hypothalamic microglia that are hyper-responsive to an immune challenge, as well as hippocampal microglia that respond less efficiently to learning. We therefore hypothesised that neonatal overfeeding would alter the ability of hippocampal microglia to respond to an immune challenge with lipopolysaccharide (LPS) and that concomitant minocycline, a tetracycline antibiotic that suppresses microglial activity, could restore these responses. We induced neonatal overfeeding by manipulating the litter sizes in which Wistar rat pups were raised, so the pups were suckled in litters of four (neonatally overfed) or 12 (control-fed). We then examined the hippocampal microglial profiles 24 hour after an immune challenge with LPS and found that the neonatally overfed rats had dramatically increased microglial numbers in the hippocampus after immune challenge compared to control-fed rats. Attempts to reverse these effects with minocycline revealed repeated that neonatal injections, whether with minocycline or with saline, markedly suppressed microglial number and density throughout the hippocampus and abolished the difference between the groups in their responses to LPS. These data suggest that neonatal overfeeding not only can have lasting effects on hippocampal immune responses, but also that neonatal exposure to a protocol of repeated injections, irrespective of treatment, has a pronounced long-term impact, highlighting the importance of considering these effects when interpreting experimental data. PMID- 28983992 TI - Registries supporting new drug applications. AB - PURPOSE: Knowledge of the benefits and risks of new drugs is incomplete at the time of marketing approval. Registries offer the possibility for additional, post approval, data collection. For all new drugs, which were approved in the European Union between 2007 and 2010, we reviewed the frequency, the type, and the reason for requiring a registry. METHODS: The European Public Assessment Reports, published on the website of the European Medicine Agency, were reviewed for drugs approved by the Committee for Medicinal Products for Human Use. We searched for key characteristics of these drugs, including therapeutic area (ATC1 level), level of innovation (the score is an algorithm based on availability of treatment and therapeutic effect), and procedural characteristics. In addition, we identified if these registries were defined by disease (disease registry) or exposure to a single drug (drug registry). RESULTS: Out of 116 new drugs approved in the predefined period, for 43 (37%), 1 to 6 registry studies were identified, with a total of 73 registries. Of these 46 were disease registries and 27 (single) drug registries. For 9 drugs, the registry was a specific obligation imposed by the regulators. The level of innovation and the orphan status of the drugs were determinants positively predicting post-approval registries (OR 10.3 [95% CI 1.0-103.9] and OR 2.8 [95% CI 1.0-7.5], respectively). CONCLUSIONS: The majority of registries required by regulators are existing disease registries. Registries are an important and frequently used tool for post-approval data collection for orphan and innovative drugs. PMID- 28983993 TI - Synthesis and Demonstration of the Biological Relevance of sp3 -rich Scaffolds Distantly Related to Natural Product Frameworks. AB - The productive exploration of chemical space is an enduring challenge in chemical biology and medicinal chemistry. Natural products are biologically relevant, and their frameworks have facilitated chemical tool and drug discovery. A "top-down" synthetic approach is described that enabled a range of complex bridged intermediates to be converted with high step efficiency into 26 diverse sp3 -rich scaffolds. The scaffolds have local natural product-like features, but are only distantly related to specific natural product frameworks. To assess biological relevance, a set of 52 fragments was prepared, and screened by high-throughput crystallography against three targets from two protein families (ATAD2, BRD1 and JMJD2D). In each case, 3D fragment hits were identified that would serve as distinctive starting points for ligand discovery. This demonstrates that frameworks that are distantly related to natural products can facilitate discovery of new biologically relevant regions within chemical space. PMID- 28983995 TI - A systematic review of qualitative evidence of cancer patients' attitudes to mindfulness. AB - Mindfulness has been described as a non-elaborative, non-judgmental, present centred awareness in which each thought, feeling or sensation is acknowledged and accepted. The aim of the present study was to systematically search and synthesise qualitative evidence of cancer patients' attitudes to mindfulness. A systematic review of qualitative evidence was conducted following the SPICE framework. All cancers were included. Medline, Cinahl, Science Direct, O-Alster and New Bank were searched from the first available year to August 2016 using the search terms; wellbeing, mindfulness, qualitative. Two reviewers independently screened titles and abstracts; potentially relevant articles were retrieved and assessed independently by two reviewers. Data were extracted and quality assessed using Critical Appraisal Skills Programme (CASP) qualitative research checklist. In total, 233 studies conducted between 2005 and 2015 were identified with six included in the final analysis. Four themes were identified: Coping strategies developed through mindfulness course; Positive outcomes of mindful practice; Challenges with engaging in mindful practice; and Group identification and shared experience. The current evidence supports the view that mindfulness is an effective intervention to help people adjust to living with and beyond cancer however, more qualitative work is needed in this area. PMID- 28983996 TI - GPs' assessment of cooperation with other health care providers involved in cancer care-a cross-sectional study. AB - Cancer is a complex disease requiring the involvement of several health care providers. A possible constant in the cancer care process is the general practitioner (GP). The aim of this project was to evaluate GPs' satisfaction with cooperation with other health care providers in the cancer care process of their patients and to explore which variables are associated with higher satisfaction with cooperation with other health care providers. We considered the following health care providers: outpatient oncology specialists, physicians in relatively small hospitals (<=400 beds), physicians in relatively large hospitals (>400 beds), home care services, outpatient psycho(onco)logists/psychotherapists, hospice/palliative care units and specialised palliative home care. The cross sectional study was carried out as a postal survey all over Germany. Data were analysed descriptively and by means of logistic regression. Overall satisfaction with cooperation with other health care providers involved in cancer care was rather high. Only cooperation with outpatient psycho(onco)logists/psychotherapists was rated as not assessable/irrelevant by a majority of GPs. For all other health care providers under review, both communication and the transfer of sufficient information in good time were associated with overall satisfaction with cooperation. Little association was found between GP and practice variables and overall satisfaction with cooperation with the considered health care providers. PMID- 28983994 TI - Chronic beta2 -adrenoceptor agonist treatment alters muscle proteome and functional adaptations induced by high intensity training in young men. AB - KEY POINTS: While several studies have investigated the effects of exercise training in human skeletal muscle and the chronic effect of beta2 -agonist treatment in rodent muscle, their effects on muscle proteome signature with related functional measures in humans are still incompletely understood. Herein we show that daily beta2 -agonist treatment attenuates training-induced enhancements in exercise performance and maximal oxygen consumption, and alters muscle proteome signature and phenotype in trained young men. Daily beta2 agonist treatment abolished several of the training-induced enhancements in muscle oxidative capacity and caused a repression of muscle metabolic pathways; furthermore, beta2 -agonist treatment induced a slow-to-fast twitch muscle phenotype transition. The present study indicates that chronic beta2 -agonist treatment confounds the positive effect of high intensity training on exercise performance and oxidative capacity, which is of interest for the large proportion of persons using inhaled beta2 -agonists on a daily basis, including athletes. ABSTRACT: Although the effects of training have been studied for decades, data on muscle proteome signature remodelling induced by high intensity training in relation to functional changes in humans remains incomplete. Likewise, beta2 agonists are frequently used to counteract exercise-induced bronchoconstriction, but the effects beta2 -agonist treatment on muscle remodelling and adaptations to training are unknown. In a placebo-controlled parallel study, we randomly assigned 21 trained men to 4 weeks of high intensity training with (HIT+beta2 A) or without (HIT) daily inhalation of beta2 -agonist (terbutaline, 4 mg dose-1 ). Of 486 proteins identified by mass-spectrometry proteomics of muscle biopsies sampled before and after the intervention, 32 and 85 were changing (false discovery rate (FDR) <=5%) with the intervention in HIT and HIT+beta2 A, respectively. Proteome signature changes were different in HIT and HIT+beta2 A (P = 0.005), wherein beta2 -agonist caused a repression of 25 proteins in HIT+beta2 A compared to HIT, and an upregulation of 7 proteins compared to HIT. beta2 Agonist repressed or even downregulated training-induced enrichment of pathways related to oxidative phosphorylation and glycogen metabolism, but upregulated pathways related to histone trimethylation and the nucleosome. Muscle contractile phenotype changed differently in HIT and HIT+beta2 A (P <= 0.001), with a fast-to slow twitch transition in HIT and a slow-to-fast twitch transition in HIT+beta2 A. beta2 -Agonist attenuated training-induced enhancements in maximal oxygen consumption (P <= 0.01) and exercise performance (6.1 vs. 11.6%, P <= 0.05) in HIT+beta2 A compared to HIT. These findings indicate that daily beta2 -agonist treatment attenuates the beneficial effects of high intensity training on exercise performance and oxidative capacity, and causes remodelling of muscle proteome signature towards a fast-twitch phenotype. PMID- 28983997 TI - Cosleeping, sleep disturbances, children's behavioral problems, and parenting self-efficacy among Korean American families. AB - The purpose of this study was to compare sleep disturbances of children and their mothers, children's behavioral problems, and parenting self-efficacy between Korean American families who coslept and those who did not cosleep. Forty-eight mothers of children between 3 and 8 years of age completed the following surveys: Children's Sleep Habits Questionnaire, Pediatric Symptom Checklist, Pittsburgh Sleep Quality Index, Parenting Self-Efficacy Questionnaire, and Acculturation Rating Scale for Mexican Americans II. Overall, 48% (n = 23) of families coslept, and families with younger children coslept more than families with older children (x2=12.48,p<.05). When the families were divided into non-cosleeping (i.e., rarely) and cosleeping (i.e., sometimes and usually) groups, 100% of the cosleeping children had sleep disturbances compared to 56% of the non-cosleeping children (x2=8.67,p<.01). For mothers, 28% (n = 7) of the non-cosleeping mothers reported sleep disturbances, compared to 52% (n = 12) of the cosleeping mothers (x2=2.93,p=.08). Children's behavioral problems were not different between the two groups (F = 1.78, p = NS). Cosleeping mothers reported lower parenting self efficacy than non-cosleeping mothers (F = 6.26, p < .05). When providing care to Korean American families with young children, their cosleeping, sleep disturbances, and parenting self-efficacy need to be addressed. PMID- 28983998 TI - Phylogeny and Redescription of the Testate Amoeba Diaphoropodon archeri (Chlamydophryidae, Thecofilosea, Cercozoa), De Saedeleer 1934, and Annotations on the Polyphyly of Testate Amoebae with Agglutinated Tests in the Cercozoa. AB - The genus Diaphoropodon, Archer 1869, comprises filose amoebae with agglutinated tests made of quartz grains, diatom frustules and other particulate materials. The key trait of the genus is a hyaline theca covered with numerous 5- to 10-MUm long, hairlike rods. Based on SSU rDNA phylogeny, we show that Diaphoropodon groups closely to Lecythium, a testate amoeba genus with a flexible but naked theca. Electron microscopic images reveal that the rods of Diaphoropodon are not perforating the test but lie randomly distributed on the surface of the amoeba. Comparing fairly naked cells from our cultures with cells from the environment leads to the conclusion that these rods play a role in agglutinating the material on the test. PMID- 28983999 TI - Impact of nurses' perceptions of work environment and communication satisfaction on their intention to quit. AB - AIM: This study examines the association of nurses' perception of their work environment and communication satisfaction with their intention to quit. METHOD: The implementation part of the study was conducted with nurses working in a public hospital in the city of Burdur, Turkey. Data were collected in January 2017 from 175 participants and then assessed. RESULTS: The analysis showed that perceptions of the work environment and communication satisfaction taken together explain the total variance of the intention to quit. While participants' perceptions of the work environment become increasingly positive, their communication satisfaction increases and their intention to quit decreases. CONCLUSION: The findings of this study suggest that making improvements to the nursing work environment and nurses' communication satisfaction will decrease their intention to quit. PMID- 28984000 TI - Phase II trial of a depression self-care intervention for adult cancer survivors. AB - Supported self-care interventions are a low-intensity treatment for depression that has received little research attention in the cancer population. This is a phase II intervention only study to test the feasibility, acceptability and preliminary effectiveness of a depression self-care intervention for cancer patients who have completed their primary treatment and have moderate depressive symptoms. The self-care intervention was adapted from a successful model for people with chronic physical conditions, following focus groups with cancer care professionals and patients. The support was delivered by telephone by a trained lay coach who provided up to 8 weekly coaching contacts. A variety of recruitment methods were tested; those with the highest yield of eligible subjects per research staff time were electronic mailings to community support group members and social media posting. Sixty-eight people were contacted about the study over an 11-month period, of whom 34 (49%) were eligible; 32 were enrolled (94% recruitment rate); and 25 completed 2-month follow-up (78% retention). The mean severity of PHQ-9 depression decreased significantly from screening to 2 months (12.8 to 7.0, p < .0001). The intervention is a promising treatment option for cancer survivors, demonstrating sufficient effectiveness and feasibility to proceed with a phase III clinical trial. PMID- 28984002 TI - Compassion for self and others as key aspects of well-being in changing times. AB - Compassion has been put forth as a core concept in caring science, although there has also been a debate over whether it is a nonprofessional sentiment or not. In this theoretical article, I reflect on compassion not only for others but also for oneself as being important for patients' as well as professionals' well being. My reflections on compassion as being essential in caring are grounded not only in caring science but also in research from other disciplines, as a means of exploring why we need compassion in caring from different perspectives. My conclusion is that in changing times, where patients as well as caregivers are confronted with challenges in life, compassion for self as well as others must be acknowledged as pivotal in relation to well-being and care. PMID- 28984001 TI - A review of the performance of different methods for propensity score matched subgroup analyses and a summary of their application in peer-reviewed research studies. AB - PURPOSE: When evaluating safety signals, there is often interest in understanding safety in all patients for whom compared treatments are reasonable alternatives, as well as in specific subgroups of interest. There are numerous ways that propensity score (PS) matching can be implemented for subgroup analyses. METHODS: We conducted a systematic literature review of methods papers that compared the performance of alternative methods to implement PS matched subgroup analyses and examined how frequently different PS matching methods have been used for subgroup analyses in applied studies. RESULTS: We identified 5 methods papers reporting small improvements in covariate balance and bias with use of a subgroup-specific PS instead of a mis-specified overall PS within subgroups. Applied research papers frequently used PS for subgroups in ways not evaluated in methods papers. Thirty three percent used PS to match in the overall cohort and broke the matched sets for subgroup analysis without further adjustment. CONCLUSIONS: While the performance of several alternative ways to use PS matching in subgroup analyses has been evaluated in methods literature, these evaluations do not include the most commonly used methods to implement PS matched subgroup analyses in applied studies. There is a need to better understand the relative performance of commonly used methods for PS matching in subgroup analyses, particularly within settings encountered during active surveillance, where there may be low exposure, infrequent outcomes, and multiple subgroups of interest. PMID- 28984004 TI - Self-reported psychological wellbeing in adolescents: the role of intellectual/developmental disability and gender. AB - BACKGROUND: The Wellbeing in Special Education Questionnaire was developed to assess subjective wellbeing in young persons with intellectual and developmental disabilities (ID/DD) as this perspective is rarely included in research. The present study explored how ID/DD and gender are related to self-reported wellbeing among adolescents. METHOD: Students with (n = 110) or without (n = 110) ID/DD, aged 12-16 years, completed the Wellbeing in Special Education Questionnaire. Analyses of the effects of gender and disability status on peer relations and conflict, mental health, mental ill-health, school environment and family relations were carried out. RESULTS: The experiences of the school environment and of positive mental health aspects did not differ between students with and without ID/DD, but those with ID/DD reported more mental health problems and less positive experiences of peer relations and family. Generally, boys reported more positive experiences of school and less mental health problems than girls. CONCLUSIONS: Including the subjective perspective of young persons with ID/DD through self-reports can provide essential information about wellbeing that cannot be gained from proxy ratings. The results suggest both differences and similarities in self-reported wellbeing between boys and girls with and without ID/DD and potentially also in how they perceived the concepts measured. PMID- 28984005 TI - Influence of perinatal low-dose acetylsalicylic acid therapy on fetal hemodynamics evaluated by determining the acceleration-time/ejection-time ratio in the ductus arteriosus. AB - AIM: Acceleration-time/ejection-time ratio (At/Et ratio) of Doppler waveform is an established hemodynamic parameters that reflect proximal stenosis. Using this parameter, we evaluated whether perinatal low-dose acetylsalicylic acid (ASA) therapy could alter hemodynamics in the ductus arteriosus. METHODS: Pulse Doppler measurements of the fetal ductus arteriosus were performed longitudinally from 20 to 37 gestational weeks in 106 healthy pregnant women (controls) and 65 pregnant women taking daily low-dose ASA (80 or 100 mg/day) because of a history of recurrent pregnancy loss. The At/Et ratio, pulsatility index (PI), and peak systolic velocity were evaluated and statistically analyzed. RESULTS: The At/Et ratio significantly increased with gestational age in both the ASA group (r = 0.54) and the control group (r = 0.35), while the PI did not. Median peak systolic velocities also increased with gestational age in both the ASA group (r = 0.39) and the control group (r = 0.31). No significant differences in At/Et ratio, PI, or peak systolic velocity were observed between the ASA group and the control group. CONCLUSION: Administration of low-dose ASA during pregnancy did not appear to alter hemodynamics in the fetal ductus arteriosus. PMID- 28984006 TI - Nosema maddoxi sp. nov. (Microsporidia, Nosematidae), a Widespread Pathogen of the Green Stink Bug Chinavia hilaris (Say) and the Brown Marmorated Stink Bug Halyomorpha halys (Stal). AB - We describe a unique microsporidian species that infects the green stink bug, Chinavia hilaris; the brown marmorated stink bug, Halyomorpha halys; the brown stink bug, Euschistus servus; and the dusky stink bug, Euschistus tristigmus. All life stages are unikaryotic, but analysis of the consensus small subunit region of the ribosomal gene places this microsporidium in the genus Nosema, which historically has been characterized by diplokaryotic life stages. It is also characterized by having the reversed arrangement of the ribosomal gene (LSU -ITS- SSU) found in species within the "true Nosema" clade. This microsporidium is apparently Holarctic in distribution. It is present in H. halys both where it is native in Asia and where it is invasive in North America, as well as in samples of North American native C. hilaris collected prior to the introduction of H. halys from Asia. Prevalence in H. halys from mid-Atlantic, North America in 2015 2016 ranged from 0.0% to 28.3%, while prevalence in C. hilaris collected in Illinois in 1970-1972 ranged from 14.3% to 58.8%. Oral infectivity and pathogenicity were confirmed in H. halys and C. hilaris. Morphological, ultrastructural, and ecological features of the microsporidium, together with a molecular phylogeny, establish a new species named Nosema maddoxi sp. nov. PMID- 28984007 TI - Navigating difficult conversations: the role of self-monitoring and reflection-in action. AB - CONTEXT: Clinicians draw upon experiential knowledge to manoeuvre difficult conversations, using tacit knowledge that is difficult to explicitly teach. Instead, learners are taught to communicate through role-play and checklists, both of which are approaches that may fail during moments of clinical complexity. We know that difficult conversations may provoke anxiety in learners, but we know little about how they learn to navigate them. Without a deeper understanding, we may fail to equip learners with the skills to manoeuvre these conversations in practice. METHODS: Using constructivist grounded theory, we applied the sensitising concepts of self-monitoring and reflection-in-action both to explore the process in which trainees engage to navigate difficult conversations and to expand understanding about these theories. We situated our research in the neonatal intensive care unit (NICU), in which difficult conversations are ubiquitous. Fifteen resident and fellow trainees drew rich pictures about difficult conversations, and shared their drawings and experiences during semi structured interviews. Interview transcripts were analysed using constant comparative analysis. RESULTS: Participants described how they responded when checklist approaches became ineffective during moments of unexpected uncertainty and complexity. For participants, these indeterminate zones of practice triggered a process of seeing families differently and then pausing to understand problems that arose with the checklist-based approach. Throughout this process, learners actively observed others' communication approaches, negotiated their roles within difficult conversations, and abandoned the checklist to engage differently with families. CONCLUSIONS: Our findings suggest links between the theories of self monitoring and reflection-in-action, and describe the engagement of both processes in the context of NICU conversations. Self-monitoring may lead to the realisation of an indeterminate zone of practice, after which trainees may respond through reflection-in-action. We recognise that training programmes may need to teach a checklist-based approach as a starting point. We suggest that trainees also be given purposeful opportunities and support to depart from checklists in order to compassionately and flexibly navigate difficult conversations with families. PMID- 28984008 TI - A response to the letter "Sleep Problems in Prison Employees" submitted to the American Journal of Industrial Medicine. PMID- 28984009 TI - MicroRNA-125b expression and intrahepatic metastasis are predictors for early recurrence after hepatocellular carcinoma resection. AB - AIM: Early hepatocellular carcinoma (HCC) recurrence after curative resection is a known poor prognostic factor. We aimed to identify microRNAs associated with recurrence after curative HCC resection. METHODS: To identify risk factors for early recurrence and metastasis, 694 patients who underwent primary curative HCC resection were analyzed. We evaluated microRNA expression in cancerous and non cancerous tissues by microarray and quantitative PCR analyses using 16 HCC samples. We defined patients who had a recurrence within 1 year of resection as the early recurrence (ER) group, patients who had a recurrence within 1-5 years as the late recurrence (LR) group, and patients who did not recur during the 5 year observation period as the no recurrence (NR) group. We examined the relationship between microRNA expression and clinical features. RESULTS: Multivariate analysis revealed that alpha-fetoprotein >31 ng/mL, tumor size >4 cm, and intrahepatic metastasis (IM) were significant factors. Afterwards, microarray analyses revealed that microRNA (miR)-125b-5p and miR-148a-3p were significantly downregulated in recurrent cases. The ratio of miR-125b-5p expression in cancerous versus non-cancerous tissue (miR-125b ratio), but not miR 148a-3p, was significantly lower in the ER group. Early recurrence was associated with reduced overall survival compared with the LR and NR group. The miR-125b ratio was significantly lower in the ER group than in the LR and NR groups. Multivariate analysis showed that a low miR-125b ratio and IM were independently associated with ER and disease-free survival. CONCLUSIONS: Assessing tissue miR 125b-5p expression and IM is useful for stratifying patients at risk of early HCC recurrence after curative resection. PMID- 28984010 TI - Safety and dose-dependency of eptacog beta (activated) in a dose escalation study of non-bleeding congenital haemophilia A or B patients, with or without inhibitors. AB - INTRODUCTION: Varying initial doses of activated eptacog beta (recombinant human FVIIa, rhFVIIa) may provide therapeutic options when treating bleeding in patients with congenital haemophilia who have developed inhibitory antibodies to factor VIII (FVIII) or factor IX (FIX). This study evaluated escalated doses of a new rhFVIIa product as a prelude to selecting the doses for clinical efficacy evaluation in haemophilia patients. AIM: To assess the safety, pharmacokinetics, and laboratory pharmacodynamics of 3 doses of rhFVIIa in non-bleeding patients with congenital haemophilia A or B with or without inhibitors. METHODS: Adult male patients (18-75 years old) with congenital haemophilia A or B (with or without inhibitors) received infusions of rhFVIIa at doses of 25, 75 or 225 MUg/kg body weight. Ten patients were treated at each dose level, and each patient received 2 different dose levels. Descriptive methods were used to analyse the data. RESULTS: Administration of rhFVIIa at all doses was well tolerated. Pharmacokinetic analyses showed that peak FVIIa plasma levels (Cmax ) were approximately proportional to dose and correlated well with peak thrombin generation. Total AUC0-inf also was approximately dose proportional. Clot formation and duration correlated with FVIIa activity. Repeat doses did not produce an immunological response. CONCLUSION: In the first dose-escalation study of rhFVIIa to support product registration, eptacog beta at doses of 25, 75, and 225 MUg/kg was pharmacodynamically active and well tolerated in non-bleeding patients with congenital haemophilia A or B. PMID- 28984011 TI - Cognitive reactions of nurses exposed to cancer patients' traumatic experiences: A qualitative study to identify triggers of the onset of compassion fatigue. AB - OBJECTIVE: Nurses in cancer care are considered to be at risk for compassion fatigue because they are frequently exposed to patients' traumatic experiences. However, only a few effective empirical studies have been conducted in this field, and cognitive factors in particular have not been sufficiently studied. This study aims to describe the components of nurses' cognitive reactions from their exposure to cancer patients' traumatic experience to the onset of compassion fatigue. METHODS: In this qualitative study, 30 nurses in cancer care were purposively selected. Data were collected through semistructured interviews and analyzed by using content analysis and the constant comparative method. RESULTS: Forty attributes were identified from 613 statements and classified into 11 categories: sense of professional inadequacy, compassion for patients and their families, desire to support patients and their families, rumination on oneself or one's family, sense of professional mission, dissatisfaction with medical staff, desire to integrate with colleagues, desire to avoid one's duties, conflict between one's belief and reality, reconsideration of the meaning of life, and sense of powerlessness over cancer. CONCLUSIONS: This study identified important components of cognitive reactions of nurses who encounter the traumatic experiences of cancer patients in Japan. This information can contribute to the understanding of the onset of compassion fatigue and provide the foundation for nurses in cancer care to avoid and recover from compassion fatigue. PMID- 28984012 TI - Sustained virological response to ombitasvir/paritaprevir/ritonavir and dasabuvir treatment for hepatitis C: Real-world data from a large healthcare provider. AB - Treatment with ombitasvir/paritaprevir/ritonavir and dasabuvir, with or without ribavirin (OPrD +/- RBV), was the first interferon-free direct-acting antiviral for hepatitis C virus (HCV) introduced to Israel's national basket of health services in February 2015. Patients with HCV genotype 1 (GT1) and advanced fibrosis (F3-F4) were eligible for treatment in 2015. This study aimed to characterize patients initiating OPrD +/- RBV and assess sustained virological response (SVR). A retrospective cohort study was performed using the database of Maccabi Healthcare Services (MHS), a 2-million-member health plan in Israel. The study population included adults who initiated OPrD +/- RBV through December 2015 per health basket criteria. A gap in medication fills (>14 days between a fill's run-out and the next fill) was used to estimate adherence. SVR was defined by the viral tests at least 12-week post-treatment. The study population consisted of 403 patients (56.3% male), with a mean age of 60.7 years (SD 11.0). Overall, 71.0% were naive to prior HCV treatment, and 95.6% were treated with a 12-week regimen. A total of 348 patients (86.4%) completed the regimen in the usual time frame (highly adherent), whereas 8.2% completed with a gap, and 4.7% purchased less than the recommended dose. SVR rates overall and among highly adherent patients were 395/403 (98.0%; 95% CI 96.1-99.1) and 346/348 (99.4%; 95% CI 97.9 99.9), respectively. GT1b patients on 12-week regimens attained SVR rates of 194/196 (fibrosis F3) and 170/176 (cirrhosis). After a first year of provision of OPrD +/- RBV with good adherence, high SVR rates were achieved in various patient subgroups and comorbidities. PMID- 28984013 TI - Transformation of MDS/MPN-RS-T to AML: Trisomy 13, resistant thrombocytosis and transient disease control with oral busulfan therapy. PMID- 28984014 TI - Increased serum C-reactive protein and decreased urinary aquaporin 2 levels are predictive of the efficacy of tolvaptan in patients with liver cirrhosis. AB - AIM: Water retention, hepatic ascites, and peripheral edema are significant problems in patients with liver cirrhosis (LC). Although furosemide and spironolactone are commonly used as treatment, they are often insufficient to treat hyponatremia and renal insufficiency in patients with LC. Tolvaptan (TVP) could provide an effective treatment alternative. However, predictive factors of a therapeutic response to TVP are unclear. Our aim was to examine clinical predictors of the response to TVP in patients with LC and water retention. METHODS: Fifty-two patients were treated with TVP, with therapeutic effects judged by a decrease in body weight (>=2 kg) and increase in urinary volume (>=500 mL) within 7 days. Blood biochemical tests were carried out at baseline and post-treatment, including serum soluble CD14 (sCD14) and urinary aquaporin 2 (AQP2) levels. Clinical and laboratory predictive factors of a TVP response were evaluated by univariate and multivariate analyses. RESULTS: The overall response to TVP was 55.8%. On univariate analyses, serum C-reactive protein (CRP) level, the neutrophil-to-lymphocyte ratio, urinary blood urea nitrogen, and urinary AQP2 were predictors of the TVP response, with only serum CRP retained on multivariate analysis. A higher serum sCD14 level was strongly associated with a non-response to TVP. A decrease in urinary AQP2 to undetectable level was associated with a response. CONCLUSION: Tolvaptan provides a rapid and strong effect to improve water retention in patients with LC. Baseline serum sCD14 and CRP levels are useful predictors of a response to TVP, with a decrease in urinary AQP2 during treatment indicating an early response. PMID- 28984015 TI - Genotype 4 hepatitis E virus is a cause of chronic hepatitis in renal transplant recipients in Hong Kong. PMID- 28984016 TI - High Sulfur Content Material with Stable Cycling in Lithium-Sulfur Batteries. AB - We demonstrate a novel crosslinked disulfide system as a cathode material for Li S cells that is designed with the two criteria of having only a single point of S S scission and maximizing the ratio of S-S to the electrochemically inactive framework. The material therefore maximizes theoretical capacity while inhibiting the formation of polysulfide intermediates that lead to parasitic shuttle. The material we report contains a 1:1 ratio of S:C with a theoretical capacity of 609 mAh g-1 . The cell gains capacity through 100 cycles and has 98 % capacity retention thereafter through 200 cycles, demonstrating stable, long-term cycling. Raman spectroscopy confirms the proposed mechanism of disulfide bonds breaking to form a S-Li thiolate species upon discharge and reforming upon charge. Coulombic efficiencies near 100 % for every cycle, suggesting the suppression of polysulfide shuttle through the molecular design. PMID- 28984017 TI - Direct Access to MIDA Acylboronates through Mild Oxidation of MIDA Vinylboronates. AB - Acylboronate esters/trifluoroborates represent an elusive class of boronates that are of increasing interest for both fundamental study as well as applications at the interface of chemistry and biology. Their preparation has been limited by the use of strongly basic anions, often introduced in multistep reactions. Herein, we demonstrate the facile preparation of acylboronate N-methyliminodiacetyl (MIDA) esters from alkenyl-2-boronate esters through mild dihydroxylation and meta periodate cleavage. Given the well-known functional-group tolerance of this mild reaction sequence and the availability of alkenyl-2-boronates, this method should greatly increase access to acylboronate MIDA esters. PMID- 28984019 TI - Non-invasive estimation of left heart filling pressures: another nail in the coffin for E/e'? PMID- 28984018 TI - The impact of improving access to primary care. AB - OBJECTIVES: To measure the size and timing of changes in utilization and costs for employees and dependents who had major access barriers to primary care removed, across an 8-year period (2007 to 2014). STUDY DESIGN AND METHODS: Retrospective observational study examining patterns of utilization and costs before and after the implementation of a worksite medical office in 2010. The worksite office offered convenient primary care services with no travel from work, essentially guaranteed same day access, and no co-pay. Trends in visit rates and costs were compared for an intervention fixed cohort group (employees and dependents) at the employer (n = 1211) with a control fixed cohort group (n = 542 162) for 6 types of visits (primary, urgent, emergency, inpatient, specialty, and other outpatient). Difference-in-differences methods assessed the significance of between-group changes in utilization and costs. RESULTS: The worksite medical office intervention group had an increase in primary care visits relative to the control group (+43% vs +4%, P < 0.001). This was accompanied by a reduction in urgent care visits by the intervention group compared with the control group (-43% vs -5%, P < 0.001). There were no differences in the other types of visits, and the total visit costs for the intervention group increased 5.7% versus 2.7% for the control group (P = 0.008). A sub-group analysis of the intervention group (comparing dependents to employees) found that that the dependents achieved a reduction in costs of 2.7% (P < 0.001) across the study period. CONCLUSIONS: The potential for long-term reduction in utilization and costs with better access to primary care is significant, but not easily nor automatically achieved. PMID- 28984020 TI - Single-Step Reagentless Laser Scribing Fabrication of Electrochemical Paper-Based Analytical Devices. AB - A single-step laser scribing process is used to pattern nanostructured electrodes on paper-based devices. The facile and low-cost technique eliminates the need for chemical reagents or controlled conditions. This process involves the use of a CO2 laser to pyrolyze the surface of the paperboard, producing a conductive porous non-graphitizing carbon material composed of graphene sheets and composites with aluminosilicate nanoparticles. The new electrode material was extensively characterized, and it exhibits high conductivity and an enhanced active/geometric area ratio; it is thus well-suited for electrochemical purposes. As a proof-of-concept, the devices were successfully employed for different analytical applications in the clinical, pharmaceutical, food, and forensic fields. The scalable and green fabrication method associated with the features of the new material is highly promising for the development of portable electrochemical devices. PMID- 28984021 TI - Conotoxin Phi-MiXXVIIA from the Superfamily G2 Employs a Novel Cysteine Framework that Mimics Granulin and Displays Anti-Apoptotic Activity. AB - Conotoxins are a large family of disulfide-rich peptides that contain unique cysteine frameworks that target a broad range of ion channels and receptors. We recently discovered the 33-residue conotoxin Phi-MiXXVIIA from Conus miles with a novel cysteine framework comprising three consecutive cysteine residues and four disulfide bonds. Regioselective chemical synthesis helped decipher the disulfide bond connectivity and the structure of Phi-MiXXVIIA was determined by NMR spectroscopy. The 3D structure displays a unique topology containing two beta hairpins that resemble the N-terminal domain of granulin. Similar to granulin, Phi-MiXXVIIA promotes cell proliferation (EC50 17.85 MUm) while inhibiting apoptosis (EC50 2.2 MUm). Additional framework XXVII sequences were discovered with homologous signal peptides that define the new conotoxin superfamily G2. The novel structure and biological activity of Phi-MiXXVIIA expands the repertoire of disulfide-rich conotoxins that recognize mammalian receptors. PMID- 28984022 TI - Disseminated erythema with intense and selective inflammation of sweat gland and lichenoid drug eruption during nivolumab therapy. PMID- 28984023 TI - Relationship between the radiation doses at nonenhanced CT studies using different tube voltages and automatic tube current modulation during anthropomorphic phantoms of young children. AB - To compare the radiation dose and image noise of nonenhanced CT scans performed at 80, 100, and 120 kVp with tube current modulation (TCM) we used anthropomorphic phantoms of newborn, 1-year-old, and 5-year-old children. The noise index was set at 12. The image noise in the center of the phantoms at the level of the chest and abdomen was measured within a circumscribed region of interest. We measured the doses in individual tissues or organs with radio photoluminescence glass dosimeters for each phantom. Various tissues or organs were assigned and the radiation dose was calculated based on the international commission on radiological protection definition. With TCM the respective radiation dose at tube voltages of 80, 100, and 120 was 29.71, 31.60, and 33.79 mGy for the newborn, 32.00, 36.79, and 39.48 mGy for the 1-year-old, and 32.78, 38.11, and 40.85 mGy for the 5-year-old phantom. There were no significant differences in the radiation dose among the tube voltages and phantoms (P > 0.05). Our comparison of the radiation dose using anthropomorphic phantoms of young children showed that the radiation dose of nonenhanced CT performed at different tube voltages with TCM was not significantly different. PMID- 28984024 TI - Nature and Strength of the Inner-Core H???H Interactions in Porphyrinoids. AB - Several recent publications have illustrated that electrostatic attraction is not solely responsible for strong hydrogen bonds. Even electropositive and less electronegative atoms such as Te and Se are capable of forming strong H-bonds. Herein, we provide evidence for intramolecular homopolar dihydrogen bonds [HOMO DHBs; X-N(C)-Hdelta+ ???delta+ H-N(C)-Y] in porphyrins and related compounds for the first time; these bonds are revealed by careful Cambridge Structural Database (CSD) exploration, quantum theory of atoms in molecules, compliance constant calculations, and natural bond orbital and noncovalent interaction (NCI) analysis. A search of the CSD showed that the inner-core hydrogen atom distances were less than 2.5 A (sum of the van der Waals radii of two hydrogen atoms is 2.4 A) in porphyrinoids, i.e. about 75 % of the cases. This suggested an attractive interaction between hydrogen atoms carrying a positive charge, which was further supported by quantum-chemical calculations. The HOMO-DHB energy in some cases was found to be as much as around 20 kJ mol-1 , which is comparable to that of any conventional H-bond energy such as for the NH3 dimer. The interplay between hyperconjugative attraction and steric constraint favorably decided the strength of the HOMO-DHBs. We expect that HOMO-DHBs could be revealed in many more systems, such as corroles, phlorins, crown ethers, and constrained systems having hydrogen atoms in close contact, and could be an important noncovalent interaction to consider in supramolecular chemistry. PMID- 28984025 TI - Hydrostatic pressure in combination with topographical cues affects the fate of bone marrow-derived human mesenchymal stem cells for bone tissue regeneration. AB - Topographical and mechanical cues are vital for cell fate, tissue development in vivo, and to mimic the native cell growth environment in vitro. To date, the combinatory effect of mechanical and topographical cues as not been thoroughly investigated. This study investigates the effect of PCL nanofiber alignment and hydrostatic pressure on stem cell differentiation for bone tissue regeneration. Bone marrow-derived human mesenchymal stem cells were seeded onto standard tissue culture plastic and electrospun random and aligned nanofibers. These substrates were either cultured statically or subjected to intermittent hydrostatic pressure at 270 kPa, 1 Hz for 60 min daily over 21 days in osteogenic medium. Data revealed higher cell metabolic activities for all mechanically stimulated cell culture formats compared with non-stimulated controls; and random fibers compared with aligned fibers. Fiber orientation influenced cell morphology and patterns of calcium deposition. Significant up-regulation of Collagen-I, ALP, and Runx-2 were observed for random and aligned fibers following mechanical stimulation; highest levels of osteogenic markers were expressed when hydrostatic pressure was applied to random fibers. These results indicate that fiber alignment and hydrostatic pressure direct stem cell fate and are important stimulus for tissue regeneration. (c) 2017 The Authors Journal of Biomedical Materials Research Part A Published by Wiley Periodicals, Inc. J Biomed Mater Res Part A: A: 629-640, 2018. PMID- 28984026 TI - Hypertension and improved left ventricular mass index in children after renal transplantation. AB - This study was conducted to evaluate the changes in BP and LVH after the transplantation and to evaluate the effect of BP changes in LVH. Forty-three pediatric renal transplant patients, with a mean age of 16.99 +/- 3.88 years, were enrolled in this study. Twenty-three (53.5%) of the patients were male. Medical records for pretransplantation period (closest to the time of transplantation) and for post-transplantation period (9-12 months after transplantation) were reviewed. All the patients had BP measurements and echocardiographic evaluation in pre- and post-transplantation period. Hypertension was defined as an average systolic and/or diastolic BP that is >=95th percentile for sex, age, and height. Although the number of patients with hypertension increased from 30 (69.76%) to 35 (81.4%), the number of patients with LVH decreased from 19 (44.1%) to 9 (20.9%) after the transplantation. Although the only significant difference in BP measurements was between the mean Z scores of 24 hour and nighttime mean DBP before and after the transplantation; the mean LVMI, and the prevalence of LVH was significantly lower after the transplantation. There was no significant correlation between the LVMI and the BP measurements. Even though hypertension may persist, there is significant improvement in LVH after renal transplantation. PMID- 28984027 TI - Influence of a preschool preventive dental programme on caries prevalence, oral care and secretory immunity to Streptococcus mutans in young adults. AB - OBJECTIVE: To evaluate oral hygiene habits, decayed, missing and filled teeth (DMFT) and surfaces (DMFS), dental care, dietetic habits and anti-Streptococcus mutans salivary secretory Immunoglobulin A (SIgA) in young adults who attended a preventive programme during preschool age. MATERIAL AND METHODS: The study group (Baby Clinic) comprised 72 patients, aged 18-25 years, who had participated in the Baby Clinic preventive programme. The control group was age- and gender matched. The patients were examined and unstimulated whole saliva was sampled for detection of anti-S. mutansSIgA antibodies. RESULTS: Control patients presented increased DMFS scores (P < .05). Hygiene habits, cariogenic diet and antibody levels were not different between groups (P > .05). Baby Clinic patients presented better periodontal status (P < .005), less calculus (P < .005) and bleeding on probing (P < .005), and reported visiting dental services more regularly (P < .05). Adjusted multivariate linear regression analysis demonstrated that DMFT was associated with study group (P < .05), gender (P < .05), parents' education (P < .05), carbohydrate intake (P < .001) and levels of anti-S. mutansSIgA (P < .007). DMFS was associated with time elapsed since the last visit to the dentist (P < .005) and weekly carbohydrate intake (P < .005). CONCLUSION: Preventive programmes for preschool children positively impact on DMFS and periodontal status in young adults, but have no long-term effects on dietary or hygiene habits. PMID- 28984029 TI - Cervicopectoral flap as an adequate decision for advanced ameloblastic carcinoma. PMID- 28984030 TI - Epigenetics for the pediatric cardiologist. AB - A genetic basis of congenital heart disease (CHD) has been known for decades. In addition to the sequence of the genome, the contribution of epigenetics to pediatric cardiology is increasingly recognized. Multiple epigenetic mechanisms, including DNA methylation, histone modification, and RNA-based regulation, are known mediators of cardiovascular disease, including both development and progression of CHD and its sequelae. Basic understanding of the concepts of epigenetics will be essential to all pediatric cardiologists in order to understand mechanisms of pathophysiology, pharmacotherapeutic concepts, and to understand the role of epigenetics in precision medicine. PMID- 28984028 TI - Linc00511 acts as a competing endogenous RNA to regulate VEGFA expression through sponging hsa-miR-29b-3p in pancreatic ductal adenocarcinoma. AB - Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy. Long non-coding RNAs (lncRNAs) are important regulators in pathological processes, yet their potential roles in PDAC are poorly understood. Here, we identify a fundamental role for a novel lincRNA, linc00511, in the progression of PDAC. Linc00511 levels in PDAC tissue specimens and cell lines were examined by quantitative real-time PCR. Corresponding adjacent non-neoplastic tissues were used as controls. The function of linc00511 in PDAC cell lines was determined by RNA interference approach in vitro and in vivo. Fluorescence in situ hybridization (FISH) was used to characterize linc00511 expression in PDAC cells. Insights of the mechanism of competitive endogenous RNAs (ceRNAs) were obtained from bioinformatic analysis, luciferase assays and RIP assays. The association between the linc00511/hsa miR29b-3p axis and VEGFA was verified by Western blotting assay. Immunohistochemistry was performed to evaluate the expression of VEGFA in PDAC samples. The aberrant up-regulation of linc00511 was detected in PDAC cell lines and patient specimens compared with controls. An increase in linc00511 expression indicates the adverse clinical pathological characteristics and poor prognosis. Functionally, linc00511 depletion in PDAC cells decreased proliferation, migration, invasion and endothelial tube formation. Mechanistically, linc00511 could up-regulate VEGFA via its competing endogenous RNA (ceRNA) activity on hsa miR-29b-3p. In summary, our results define an important axis controlling proliferation, invasion and tumour angiogenesis in PDAC. Linc00511 is a novel lncRNA that plays a significant regulatory role in the pathogenesis and progression of PDAC. Thus, Linc00511 represents a new prognostic biomarker to predict clinical outcome of PDAC patients after surgery and may serve as a potential therapeutic target for PDAC treatment. PMID- 28984031 TI - Performance evaluation of the Spinit(r) -BC, a new point-of-care assay for total WBC count with 5-part differential and hematocrit measurement. PMID- 28984032 TI - Effects of dietary selenium and moisture on the physical activity and thyroid axis of cats. AB - Consumption of canned cat food is considered a risk factor for the development of feline hyperthyroidism. Because selenium and water are substantially higher in canned diets compared to dry diets, objectives of this study were to determine whether increased dietary selenium or water alters the function of the hypothalamic-pituitary-thyroid axis and leads to an increase in activity level. Employing a 28-day latin square design with a 14-day washout, six lean, neutered male domestic shorthair cats were fed (i) commercially available adult dry feline diet containing 0.8 ppm selenium (control), (ii) control diet with added sodium selenite to achieve a dietary selenium concentration of 1.125 ppm (selenium treatment) and (iii) the control diet with additional water to achieve a moisture content of 75% wt/wt (water treatment). Water consumption was determined using deuterium oxide washout. Actical activity monitors were placed on each cat's collar to allow quantification of the activity of each cat. Circulating serum T3 and T4 was measured on days 0, 14, and 28. On day 28, a thyrotropin-releasing hormone (TRH) stimulation test was conducted to determine treatment effects on serum concentrations of thyroid hormones. There was a significant increase in daily water consumption with dietary water treatment (192 ml +/- 7.85 SEM) compared to the control (120 ml +/- 20.4) and selenium (116 ml +/- 14.6) treatments. Both water and selenium treatments were associated with greater (p < .05) activity over that of the control treatment by 20.5% and 11% respectively. Serum TT3 AUC concentrations (0-4 hr) of TRH stimulation tests were greater (p < .05) by 16% with water compared to control treatments. The results of this study indicate that dietary water content may alter the function of the thyroid axis and that this effect is associated with an increase in physical activity. PMID- 28984033 TI - Two-year follow-up of a postpartum weight loss intervention: Results from a randomized controlled trial. AB - We recently reported that a 12-week diet intervention among postpartum women produced a weight loss of 12% after 1 year, compared to 5% in controls. Here, we present 2-year results after 1 year of unsupervised follow-up. In total, 110 women with a self-reported body mass index of >=27 kg/m2 at 6-15-week postpartum were randomized to diet group (D-group) or control group (C-group). D-group received a 12-week diet intervention by a dietitian followed by monthly e-mails up to the 1-year follow-up. C-group received a brochure on healthy eating. No contact was provided from 1 to 2 years to either group. Eighty-nine women (81%) completed the 2-year follow-up. Median (1st; 3rd quartile) weight change from 0 to 2 years was -6.9 (-11.0; -2.2) kg in D-group and -4.3 (-8.7; -0.2) kg in C group. There was no group by time interaction at 2 years (p = .082); however, when women with a new pregnancy between 1 and 2 years were excluded, the interaction became significant (-8.2 vs. -4.6 kg, p = .038). From 1 to 2 years, women in D- and C-group gained 2.5 +/- 5.0 kg and 1.1 +/- 4.4 kg, respectively (p = .186). Women who gained weight from 1 to 2 years reported a decrease in self weighing frequency compared to women who maintained or lost weight (p = .008). Both groups achieved clinically relevant 2-year weight loss, but the significant between-group-difference observed at 1 year was not maintained at 2 years in the main analysis. However, when women with a new pregnancy between 1 and 2 years were excluded, a significant weight loss effect was observed also at 2 years. PMID- 28984034 TI - Microcystin-LR disrupts insulin signaling by hyperphosphorylating insulin receptor substrate 1 and glycogen synthase. AB - Microcystin-LR (MC-LR) is a cyanobacteria-derived heptapeptide that has been commonly characterized as a hepatotoxin. Although the liver is a primary organ in glucose homeostasis, the effect of MC-LR on glucose metabolism remains unclear. In this study, the human liver cell line HL7702 and ICR mice were exposed to various concentrations of MC-LR for 24 h, and the proteins involved in insulin signaling were investigated. The results showed that MC-LR treatment induced the hyperphosphorylation of insulin receptor substrate 1 (IRS1) at several serine sites, S307, S323, S636/639, and S1101 in HL7702 cells, and S302, S318, S632/635, and S1097 in mice livers. In addition, the activation of S6K1 was demonstrated to play an important role in MC-LR-induced IRS1 hyperphosphorylation at several serine sites. Decreased levels of total IRS1 were observed in the mice livers, but there was no significant change in HL7702 cells. MC-LR also induced glycogen synthase (GS) hyperphosphorylation at S641 (inactivating GS) both in vitro and in vivo, even glycogen synthase kinase 3, a well-known GS kinase, was inactivated after MC-LR treatment. Moreover, MC-LR could block insulin-induced GS activation. In addition, glucose transport in liver cells was not impacted by MC-LR either with or without insulin stimulation. Our study implies that MC-LR can interfere with the actions of IRS1 and GS in insulin signaling and may have a toxic effect on glucose metabolism in the liver. PMID- 28984035 TI - Carney complex revealed by a cerebellar ischaemic stroke in a 6-year-old girl. PMID- 28984036 TI - A cross-sectional study of intestinal parasitoses in dogs and children of the periurban area of La Plata (Buenos Aires, Argentina): Zoonotic importance and implications in public health. AB - A cross-sectional study was performed between school term dates 2014 and 2015 to diagnose intestinal parasites in dogs and children living with them. The socio environmental characteristics and hygiene practices of the children were also evaluated in terms of risk factors for parasitic infection of periurban neighbourhoods of La Plata (Buenos Aires, Argentina). Serial coproparasitological samples of 78 dogs and 211 children were analysed by means of concentration and flotation techniques. Socio-environmental variables and hygiene practices of children were evaluated through semi-structured questionnaires which were answered by every family. The study showed that 82.1% of dogs were parasitized. The specific richness was of 11 species; Ancylostoma caninum (69.2%), Uncinaria stenocephala (41.0%), Trichuris vulpis (28.2%) and Toxocara canis (21.8%) were the most prevalent. The study also revealed that 67.8% of children were positive. Also, 11 species were identified and the most prevalent were Blastocystis sp. (36.0%), Enterobius vermicularis (27.5%) and Giardia lamblia (21.3%). The risk for parasitosis was higher in 6-year-old children and older (OR = 1.9, 95% IC: 1.0-3.7) and in those who did not wash their hands or did it occasionally after playing with their pets (OR = 2.8, 95% IC: 1.4-5.5). Blastocystis sp. and Entamoeba coli infection risks were greater in children whose parents had a basic level of education (OR = 3.4, 95% IC: 1.3-8.7 and OR = 3.6, 95% IC: 0.8-15.9, respectively). In addition, the risk of infection for E. coli was higher in children who lived in floodable houses (OR = 4.4, 95% IC: 0.9-16.6). Likewise, the risk of infection for E. vermicularis was greater in children with onychophagia (OR = 1.6, 95% IC: 0.7-3.7) and in 6 year olds and older whose parents completed only primary studies (OR = 3.6, 95% IC: 1.4-9.1). The results obtained show the existence of a worrying epidemiological scenario that stresses the importance of zoonotic parasitosis as a serious problem of public health. PMID- 28984037 TI - Clinical and pathological feature of bone marrow granulomas: A modern Australian series. AB - INTRODUCTION: Marrow granulomas have been commonly associated with mycobacterial infections, prompting extensive investigations in some cases where they are found, but in the setting of changing infectious epidemiology, there is a lack of recent data to guide the search for probable causes. METHODS: A retrospective case series examining the clinical and pathological findings in all cases where marrow granulomas were reported over a 10-year period at The Canberra Hospital, Australia. RESULTS: Of the 6062 marrow biopsies performed, 73 (1.2%) from 66 individuals had confirmed granulomas. Some patients had multiple potential causes found. B-cell non-Hodgkin Lymphoma, sarcoidosis and autoimmune disease were the most frequently observed causes. Infections were less common in this cohort than in the previous series, with no tuberculosis seen. The presence of granulomas in the marrow did not signify the presence of active malignancy in the marrow. There were no associations with any specific morphological characteristics of the granulomas and the presumed causes. CONCLUSION: Marrow granulomas are seen in a variety conditions. Neither their presence nor their morphological features are a guide to further investigations, which should be determined by the clinical presentation as appropriate. PMID- 28984038 TI - Beta-cell replacement strategies for diabetes. AB - Diabetes is characterized by elevated levels of blood glucose as a result of insufficient production of insulin from loss or dysfunction of pancreatic islet beta-cells. Here, we review several approaches to replacing beta-cells that were recently discussed at a symposium held in Kyoto, Japan. Transplant of donor human islets can effectively treat diabetes and eliminate the need for insulin injections, supporting research aimed at identifying abundant supplies of cells. Studies showing the feasibility of producing mouse islets in rats support the concept of generating pigs with human pancreas that can serve as donors of human islets, although scientific and ethical challenges remain. Alternatively, in vitro differentiation of both human embryonic stem cells and induced pluripotent stem cells is being actively pursued as an islet cell source, and embryonic stem cell-derived pancreatic progenitor cells are now in clinical trials in North America in patients with diabetes. Macro-encapsulation devices are being used to contain and protect the cells from immune attack, and alternate strategies of immune-isolation are being pursued, such as islets contained within long microfibers. Recent advancements in genetic engineering tools offer exciting opportunities to broaden therapeutic strategies and to probe the genetic involvement in beta-cell failure that contributes to diabetes. Personalized medicine might eventually become a possibility with genetically edited patient induced pluripotent stem cells, and the development of simplified robust differentiation protocols that ideally become standardized and automated. Additional efforts to develop a safe and effective beta-cell replacement strategy to treat diabetes are warranted. PMID- 28984039 TI - Small Molecule Antagonist of Cell Surface Glycosaminoglycans Restricts Mouse Embryonic Stem Cells in a Pluripotent State. AB - Recently, the field of stem cell-based regeneration has turned its attention toward chemical approaches for controlling the pluripotency and differentiation of embryonic stem cells (ESCs) using drug-like small molecule modulators. Growth factor receptors or their associated downstream kinases that regulate intracellular signaling pathways during differentiation are typically the targets for these molecules. The glycocalyx, which plays an essential role in actuating responses to growth factors at the cellular boundary, offers an underexplored opportunity for intervention using small molecules to influence differentiation. Here, we show that surfen, an antagonist of cell-surface glycosaminoglycans required for growth factor association with cognate receptors, acts as a potent and general inhibitor of differentiation and promoter of pluripotency in mouse ESCs. This finding shows that drugging the stem cell Glycome with small molecules to silence differentiation cues can provide a powerful new alternative to existing techniques for controlling stem cell fate. Stem Cells 2018;36:45-54. PMID- 28984040 TI - Equine chlamydiosis-An emerging infectious disease requiring a one health surveillance approach. AB - Psittacosis is a rare but potentially fatal zoonosis caused by Chlamydia psittaci, an organism that is typically associated with bird contact. However C. psittaci is capable of infecting other non-avian hosts, such as horses, sheep, cattle and goats. Stud staff and veterinarians have significant exposure to parturient animals and reproductive materials in their routine work. To investigate the zoonotic potential associated with the emergence of C. psittaci as an abortifacient agent in horses, we established a programme of joint human and animal surveillance in a sentinel horse-breeding region in Australia. This programme comprised cross-notification of equine cases to public health agencies, and active follow-up of known human contacts, including stud workers, foaling staff, veterinarians and laboratory staff. We identified no confirmed cases of acute psittacosis despite intensive surveillance and testing of heavily exposed contacts; however, further work in the area is needed. PMID- 28984041 TI - Safety and efficacy of the combination of the glucagon-like peptide-1 receptor agonist liraglutide with an oral antidiabetic drug in Japanese patients with type 2 diabetes: Post-hoc analysis of a randomized, 52-week, open-label, parallel group trial. AB - AIMS/INTRODUCTION: The aim of the present post-hoc analysis was to investigate the safety and efficacy of liraglutide in combination with one oral antidiabetic drug (OAD) across different OAD classes. MATERIALS AND METHODS: This was a post hoc analysis using data from a 52-week, open-label, parallel-group trial, in which patients with type 2 diabetes inadequately controlled with a single OAD (alpha-glucosidase inhibitor, glinide, metformin or thiazolidinedione) were randomized to either pretrial OAD in combination with liraglutide 0.9 mg/day (liraglutide group) or pretrial OAD in combination with an additional OAD (additional OAD group). The primary outcome investigated in this post-hoc analysis was the incidence of adverse events. RESULTS: The proportions of patients experiencing adverse events across the different groups of pretrial OADs were comparable between liraglutide and additional OAD (alpha-glucosidase inhibitor 74.6 vs 70.0%; glinide 93.1 vs 87.1%; metformin 91.8 vs 87.1%; thiazolidinedione 86.2 vs 96.4%, respectively). Minor hypoglycemia was infrequent (seven episodes in two patients randomized to liraglutide, and two episodes in two patients randomized to additional OAD). The mean reduction in glycated hemoglobin appeared greater with liraglutide therapy, with the estimated mean treatment difference (95% confidence interval [CI]) for liraglutide vs additional OAD ranging from -0.14%, 95% CI: -0.48 to 0.21 (-1.5 mmol/mol, 95 CI: -5.2 to 2.3) to -0.44%, 95% CI:-0.79 to -0.09 (-4.8 mmol/mol, 95% CI: -8.6 to -1.0). CONCLUSIONS: The present analysis suggests that Japanese patients on OAD monotherapy might benefit from a greater improvement in glycemic control, without impacting tolerability, by combining their OAD with liraglutide rather than another OAD, regardless of which OAD monotherapy they are receiving. PMID- 28984042 TI - Rates and predictors of disengagement of patients with first-episode psychosis from the early intervention service for sychosis service (EASY) covering 15 to 64 years of age in Hong Kong. AB - AIM: This study aims at assessing the rate and predictors of disengagement of patients with first-episode psychosis (FEP) from the early intervention (EI) service in Hong Kong (EASY) that covers age 15 to 64. METHODS: All FEP patients aged 15 to 64 years who were newly registered with the EASY programme of Kowloon West Psychiatric Unit from January to December 2012 were included. Data on socio demographic, clinical characteristics and disengagement over 3 years of the EI service were obtained retrospectively through systematic clinical record review. Predictors of 3 different types of disengagement and their rate of occurrence were identified: complete disengagement (type I), disengaged and re-engaged through hospitalization (type II) and re-engaged as outpatient (type III). RESULTS: Among the 277 patients included for analysis, 36 patients (13%) had type I disengagement, 17.2% (N = 21) were of age 15 to 25 and 9.7% (N = 15) were of age 25 to 64. Type II and type III disengagements were 4.3% and 13.4%, respectively. Early-stage poor drug compliance significantly predicted type I and type II disengagements. History of substance use, suicidal attempts and poor drug compliance predicted type III disengagement. Younger patients had significant earlier disengagement (chi2 = 5.01, df = 1, P = .025). CONCLUSION: Results of the current study highlighted the different patterns of disengagement for different age groups and the importance of identifying the high-risk group at early stage of the illness. With the expansion of EI service for wider age group, studies of the differential needs of patient with different ages would be important to guide the future service development. PMID- 28984043 TI - Metabolic nuclear receptors in periodontal host-microbe interactions and inflammation. PMID- 28984044 TI - An engineered tendon/ligament bioscaffold derived from decellularized and demineralized cortical bone matrix. AB - Demineralized bone matrix (DBM), as an extracellular matrix (ECM), has had limited use as a medical replacement although studies have reported a possibility for its use in tendon or ligament tissue engineering. To be an acid-extracted organic matrix, DBM contains much of bone protein, with a small amount of inorganic solids and some cell debris. However, cell debris is a critical factor that triggers inflammatory reaction in clinical reconstructions using ECM. In this study, we used a protocol incorporating the use of detergent with nuclease treatment to prepare decellularized DBM (DCDBM). DNA quantification analysis and histological observation confirmed that cells were completely removed from DBM. The inherent ultrastructure of DBM was well preserved after decellularization as observed through scanning electron microscopy. Additionally, calcium and phosphorus were absent and the specific functional groups of collagen remained after decellularization. Moreover, 79.71% of the tensile strength of DBM was retained and the viscoelastic properties were similar to the ligament. Furthermore, DCDBM promoted the adhesion and proliferation of NIH-3T3 fibroblasts in vitro and triggered less inflammation response at 12 weeks subcutaneous implantation in a rat model. These results demonstrate that the DCDBM has the potential to be used for tendon and ligament replacement. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 468-478, 2018. PMID- 28984045 TI - Differentially expressed alternatively spliced genes in skeletal muscle from cancer patients with cachexia. AB - BACKGROUND: Alternative splicing (AS) is a post-transcriptional gene regulatory mechanism that contributes to proteome diversity. Aberrant splicing mechanisms contribute to various cancers and muscle-related conditions such as Duchenne muscular dystrophy. However, dysregulation of AS in cancer cachexia (CC) remains unexplored. Our objectives were (i) to profile alternatively spliced genes (ASGs) on a genome-wide scale and (ii) to identify differentially expressed alternatively spliced genes (DASGs) associated with CC. METHODS: Rectus abdominis muscle biopsies obtained from cancer patients were stratified into cachectic cases (n = 21, classified based on International consensus diagnostic framework for CC) and non-cachectic controls (n = 19, weight stable cancer patients). Human transcriptome array 2.0 was used for profiling ASGs using the total RNA isolated from muscle biopsies. Representative DASG signatures were validated using semi quantitative RT-PCR. RESULTS: We identified 8960 ASGs, of which 922 DASGs (772 up regulated and 150 down-regulated) were identified at >=1.4 fold-change and P < 0.05. Representative DASGs validated by semi-quantitative RT-PCR confirmed the primary findings from the human transcriptome arrays. Identified DASGs were associated with myogenesis, adipogenesis, protein ubiquitination, and inflammation. Up to 10% of the DASGs exhibited cassette exon (exon included or skipped) as a predominant form of AS event. We also observed other forms of AS events such as intron retention, alternate promoters. CONCLUSIONS: Overall, we have, for the first time, conducted global profiling of muscle tissue to identify DASGs associated with CC. The mechanistic roles of the identified DASGs in CC pathophysiology using model systems is warranted, as well as replication of findings in independent cohorts. PMID- 28984047 TI - Using Z-scores to evaluate levator hiatal dimensions with four-dimensional translabial ultrasound. AB - AIM: This study represents the first attempt to use 'Z-scores' to assess levator hiatal dimensions and quantify hiatal expansion. METHODS: We undertook a retrospective study on the data of 110 nulliparae and 73 pelvic organ prolapse (POP) patients who had a clinical POP exam and translabial 4-D ultrasound. We used Z-scores to normalize the dimensions of nulliparae levator hiatus and to build a Z-score model to evaluate the 'hiatal ballooning' against the POP staging. RESULTS: Valid data were gathered from 102 nulliparae and 64 POP patients. We built the Z-score models as follows: Z-Av = (measured value - 17.19) / 2.98, Z-Lv = (measured value - 55.65) / 5.48, where 'Av' and 'Lv' represented the 'hiatal area' and the 'anterior-posterior diameter' on Valsalva, respectively. The '90% reference range' of Z-Av was (-1.8-+1.8) and that of Z-Lv was (-2.0-+2.0). On receiver-operator curve analysis, the cut-off against POP stage 2 for Av was 20 cm2 (sensitivity of 79%, specificity of 66%), and that for Lv was 6.0 cm (sensitivity of 68%, specificity of 65%), which were approximately equal to a Z-Av of 1.0 and a Z-Lv of 1.0, correspondingly. For POP stage 3, the cut-off was an Av of 24 cm2 (sensitivity of 85%, specificity of 83%) or an anterior-posterior diameter of 6.3 cm (sensitivity of 77%, specificity of 80%), which was approximately equal to a Z-Av of 2.0 or a Z-Lv of 1.5, respectively. CONCLUSION: 'Normal hiatal dimension' was defined as Z-Av <= 1.0 or Z-Lv <= 1.0, and 'hiatal ballooning' was defined as Z-Av >= 2.0 or Z-Lv >= 1.5. PMID- 28984046 TI - Inhibition of telomerase activity and induction of apoptosis by Rhodospirillum rubrum L-asparaginase in cancer Jurkat cell line and normal human CD4+ T lymphocytes. AB - Rhodospirillum rubrum L-asparaginase mutant E149R, V150P, F151T (RrA) down regulates telomerase activity due to its ability to inhibit the expression of telomerase catalytic subunit hTERT. The aim of this study was to define the effect of short-term and long-term RrA exposure on proliferation of cancer Jurkat cell line and normal human CD4+ T lymphocytes. RrA could inhibit telomerase activity in dose- and time-dependent manner in both Jurkat and normal CD4+ T cells. Continuous RrA exposure of these cells resulted in shortening of telomeres followed by cell cycle inhibition, replicative senescence, and development of apoptosis. Complete death of Jurkat cells was observed at the day 25 of RrA exposure while normal CD4+ T cells died at the day 50 due to the initial longer length of telomeres. Removal of RrA from senescent cells led to a reactivation of hTERT expression, restoration telomerase activity, re-elongation of telomeres after 48 h of cultivation, and survival of cells. These findings demonstrate that proliferation of cancer and normal telomerase-positive cells can be limited by continuous telomerase inhibition with RrA. Longer telomeres of normal CD4+ T lymphocytes make such cells more sustainable to RrA exposure that could give them an advantage during anti-telomerase therapy. These results should facilitate further investigations of RrA as a potent anti-telomerase therapeutic protein. PMID- 28984048 TI - Antibiotic pretreatment minimizes dietary effects on reconstructure of rumen fluid and mucosal microbiota in goats. AB - We used 16S rRNA gene sequencing to examine the posteffects of antibiotic treatment on the structure and metabolism of rumen microbiota. Twelve goats were randomly assigned into two groups, with one group receiving intramuscular streptomycin injection at 40 mg/kg bodyweight daily for 10 days. At 4 weeks after treatment with antibiotic, three goats were randomly selected from each group and switched to a 35% concentrate diet. The remaining six goats continued with the 10% concentrate diet. At 4 weeks after dietary shift, ruminal fluid and epithelium were collected to analyze the microbiota composition and short-chain fatty acid (SCFA) concentrations of the rumen. We found that antibiotic administration led to increases in the diversity and richness of recovered mucosal microbiota and to decreases in those of recovered fluid microbiota. When dietary modulation was performed after antibiotic intake, both communities showed little difference in structure from premodulated states. Additionally, antibiotic pretreatment reduced the basal lines of individual SCFAs but did not affect the increased percentages of SCFAs. Overall, our results indicate that antibiotic administration affects the structure of both rumen fluid and mucosal microbiota and reduces the functional redundancy of rumen microbiota. PMID- 28984049 TI - miR-422a suppresses SMAD4 protein expression and promotes resistance to muscle loss. AB - BACKGROUND: Loss of muscle mass and strength are important sequelae of chronic disease, but the response of individuals is remarkably variable, suggesting important genetic and epigenetic modulators of muscle homeostasis. Such factors are likely to modify the activity of pathways that regulate wasting, but to date, few such factors have been identified. METHODS: The effect of miR-422a on SMAD4 expression and transforming growth factor (TGF)-beta signalling were determined by western blotting and luciferase assay. miRNA expression was determined by qPCR in plasma and muscle biopsy samples from a cross-sectional study of patients with chronic obstructive pulmonary disease (COPD) and a longitudinal study of patients undergoing aortic surgery, who were subsequently admitted to the intensive care unit (ICU). RESULTS: miR-422a was identified, by a screen, as a microRNA that was present in the plasma of patients with COPD and negatively associated with muscle strength as well as being readily detectable in the muscle of patients. In vitro, miR-422a suppressed SMAD4 expression and inhibited TGF-beta and bone morphogenetic protein-dependent luciferase activity in muscle cells. In male patients with COPD and those undergoing aortic surgery and on the ICU, a model of ICU-associated muscle weakness, quadriceps expression of miR-422a was positively associated with muscle strength (maximal voluntary contraction r = 0.59, P < 0.001 and r = 0.51, P = 0.004, for COPD and aortic surgery, respectively). Furthermore, pre-surgery levels of miR-422a were inversely associated with the amount of muscle that would be lost in the first post-operative week (r = -0.57, P < 0.001). CONCLUSIONS: These data suggest that differences in miR-422a expression contribute to the susceptibility to muscle wasting associated with chronic and acute disease and that at least part of this activity may be mediated by reduced TGF-beta signalling in skeletal muscle. PMID- 28984050 TI - Comparison of the ability of double-robust estimators to correct bias in propensity score matching analysis. A Monte Carlo simulation study. AB - OBJECTIVE: As covariates are not always adequately balanced after propensity score matching and double- adjustment can be used to remove residual confounding, we compared the performance of several double-robust estimators in different scenarios. METHODS: We conducted a series of Monte Carlo simulations on virtual observational studies. After estimating the propensity scores by logistic regression, we performed 1:1 optimal, nearest-neighbor, and caliper matching. We used 4 estimators on each matched sample: (1) a crude estimator without double adjustment, (2) double-adjustment for the propensity scores, (3) double adjustment for the unweighted unbalanced covariates, and (4) double-adjustment for the unbalanced covariates, weighted by their strength of association with the outcome. RESULTS: The crude estimator led to highest bias in all tested scenarios. Double-adjustment for the propensity scores effectively removed confounding only when the propensity score models were correctly specified. Double-adjustment for the unbalanced covariates was more robust to misspecification. Double-adjustment for the weighted unbalanced covariates outperformed the other approaches in every scenario and using any matching algorithm, as measured by the mean squared error. CONCLUSION: Double-adjustment can be used to remove residual confounding after propensity score matching. The unbalanced covariates with the strongest confounding effects should be adjusted. PMID- 28984051 TI - Fetal retroesophageal left brachiocephalic vein with U-shaped vascular ring on four-dimensional color Doppler ultrasound. PMID- 28984052 TI - Patterns of long-term use of non-vitamin K antagonist oral anticoagulants for non valvular atrial fibrillation: Quebec observational study. AB - PURPOSE: Studies on long-term utilization of non-vitamin K antagonist oral anticoagulants (NOACs) in non-valvular atrial fibrillation (NVAF) are scarce. We evaluated predictors of use and long-term persistence of NOACs in a real-world setting. METHODS: This population-based cohort study used the computerized databases of the Canadian Province of Quebec's health insurance. Patients with a first NVAF diagnosis from 2011 until 2014 were included. A logistic regression model yielded adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for predictors of treatment initiation with NOACs versus VKAs. Cox proportional hazards models yielded adjusted hazard ratios (HRs) and 95% CIs for predictors of switching from VKAs to NOACs versus remaining on VKAs, and for predictors of discontinuation of anticoagulation treatment. RESULTS: Of the 62 867 newly diagnosed NVAF patients, 14 646 initiated NOACs and 17 685 VKAs. Initiation with NOACs was less likely for patients >= 80 years old (OR 0.55, 95% CI 0.41-0.73) or with CHA2 DS2 -VASc >= 2 (OR 0.49, 95% CI 0.42-0.57). Switching from VKAs to NOACs was less likely for patients with chronic kidney disease (HR 0.53, 95% CI 0.48-0.59). After 3 years, persistence was 54% with NOACs and 25% with VKAs. Discontinuation of anticoagulation treatment was less likely for patients >= 80 years old (HR 0.47, 95% CI 0.40-0.55) or with CHA2 DS2 -VASc >= 2 (HR 0.64, 95% CI 0.57-0.70). CONCLUSIONS: Older, high-risk patients are less likely to initiate NOACs than VKAs. NOAC users show a higher long-term persistence than VKA users, and older, high-risk patients are less likely to discontinue anticoagulation treatment. PMID- 28984054 TI - RNA uridylation: a key posttranscriptional modification shaping the coding and noncoding transcriptome. AB - RNA uridylation is a potent and widespread posttranscriptional regulator of gene expression. RNA uridylation has been detected in a range of eukaryotes including trypanosomes, animals, plants, and fungi, but with the noticeable exception of budding yeast. Virtually all classes of eukaryotic RNAs can be uridylated and uridylation can also tag viral RNAs. The untemplated addition of a few uridines at the 3' end of a transcript can have a decisive impact on RNA's fate. In rare instances, uridylation is an intrinsic step in the maturation of noncoding RNAs like for the U6 spliceosomal RNA or mitochondrial guide RNAs in trypanosomes. Uridylation can also switch specific miRNA precursors from a degradative to a processing mode. This switch depends on the number of uridines added which is regulated by the cellular context. Yet, the typical consequence of uridylation on mature noncoding RNAs or their precursors is to accelerate decay. Importantly, mRNAs are also tagged by uridylation. In fact, the advent of novel high throughput sequencing protocols has recently revealed the pervasiveness of mRNA uridylation, from plants to humans. As for noncoding RNAs, the main function to date for mRNA uridylation is to promote degradation. Yet, additional roles begin to be ascribed to U-tailing such as the control of mRNA deadenylation, translation control and possibly storage. All these new findings illustrate that we are just beginning to appreciate the diversity of roles played by RNA uridylation and its full temporal and spatial implication in regulating gene expression. WIREs RNA 2018, 9:e1440. doi: 10.1002/wrna.1440 This article is categorized under: RNA Processing > 3' End Processing RNA Processing > RNA Editing and Modification RNA Turnover and Surveillance > Turnover/Surveillance Mechanisms. PMID- 28984053 TI - Ten-year immune persistence and safety of the HPV-16/18 AS04-adjuvanted vaccine in females vaccinated at 15-55 years of age. AB - Women remain at risk of human papillomavirus (HPV) infection for most of their lives. The duration of protection against HPV-16/18 from prophylactic vaccination remains unknown. We investigated the 10-year immune response and long-term safety profile of the HPV-16/18 AS04-adjuvanted vaccine (AS04-HPV-16/18 vaccine) in females aged between 15 and 55 years at first vaccination. Females who received primary vaccination with three doses of AS04-HPV-16/18 vaccine in the primary phase-III study (NCT00196937) were invited to attend annual evaluations for long term immunogenicity and safety. Anti-HPV-16/18 antibodies in serum and cervico vaginal secretions (CVS) were measured using enzyme-linked immunosorbent assay (ELISA). Serious adverse events (SAEs) were recorded throughout the follow-up period. Seropositivity rates for anti-HPV-16 remained high (>=96.3%) in all age groups 10 years after first vaccination. It was found that 99.2% of 15-25-year olds remained seropositive for anti-HPV-18 compared to 93.7% and 83.8% of 26-45 year olds and 45-55-year olds, respectively. Geometric mean titers (GMT) remained above natural infection levels in all age groups. Anti-HPV-16 and anti-HPV-18 titers were at least 5.3-fold and 3.1-fold higher than titers observed after natural infection, respectively, and were predicted to persist above natural infection levels for >=30 years in all age groups. At Year 10, anti-HPV-16/18 antibody titers in subjects aged 15-25 years remained above plateau levels observed in previous studies. Correlation coefficients for antibody titers in serum and CVS were 0.64 (anti-HPV-16) and 0.38 (anti-HPV-18). This study concluded that vaccinated females aged 15-55 years elicited sustained immunogenicity with an acceptable safety profile up to 10 years after primary vaccination, suggesting long-term protection against HPV. PMID- 28984056 TI - Functional oxygen extraction fraction (OEF) imaging with turbo gradient spin echo QUIXOTIC (Turbo QUIXOTIC). AB - PURPOSE: QUantitative Imaging of eXtraction of Oxygen and TIssue Consumption (QUIXOTIC) is a recent technique that measures voxel-wise oxygen extraction fraction (OEF) but suffers from long scan times, limiting its application. We implemented multiecho QUIXOTIC dubbed turbo QUIXOTIC (tQUIXOTIC) that reduces scan time eightfold and then applied it in functional MRI. METHODS: tQUIXOTIC utilizes a novel turbo gradient spin echo readout enabling measurement of venular blood transverse relaxation rate in a single tag-control acquisition. Using tQUIXOTIC, we estimated cortical gray matter (GM) OEF, created voxel-by-voxel GM OEF maps, and quantified changes in visual cortex OEF during a blocked design flashing checkerboard visual stimulus. Contamination from cerebrospinal fluid partial volume averaging was estimated and corrected. RESULTS: The average cortical GM OEF was estimated as 0.38 +/- 0.06 (n = 8) using a 3.4-min acquisition. The average OEF in the visual cortex was estimated as 0.43 +/- 0.04 at baseline and 0.35 +/- 0.05 during activation, with an average %DeltaOEF of 20%. These values are consistent with those of past studies. CONCLUSION: tQUIXOTIC successfully estimated cortical GM OEF in clinical scan times and detected changes in OEF during blocked design visual stimulation. tQUIXOTIC will be useful to monitor regional OEF clinically and in blocked design or event related functional MRI experiments. Magn Reson Med 79:2713-2723, 2018. (c) 2017 International Society for Magnetic Resonance in Medicine. PMID- 28984057 TI - Echocardiographic estimation of left ventricular and pulmonary pressures in patients with heart failure and preserved ejection fraction: a study utilizing simultaneous echocardiography and invasive measurements. AB - AIMS: Although echocardiography is generally used for the diagnosis of heart failure with preserved ejection fraction (HFpEF), invasive measurements of filling pressures are the gold standard. Studies simultaneously performing echocardiography and invasive measurements in HFpEF are sparse. METHODS AND RESULTS: Invasive haemodynamic and echocardiographic measurements were simultaneously performed in 98 patients with heart failure New York Heart Association class >=II, left ventricular ejection fraction (LVEF) >=45%, and suspected pulmonary hypertension on a previous echocardiogram. Multivariable linear regression analyses were used to establish echocardiographic predictors of pulmonary artery wedge pressure (PAWP), left ventricular end-diastolic pressure (LVEDP), and mean pulmonary arterial pressure (mPAP). Mean age of the study patients was 74 +/- 9 years, 68% were female, mean LVEF was 57 +/- 5%, and 30% had atrial fibrillation at the time of measurement. Mean PAWP, LVEDP and mPAP were 17.2 +/- 6.2, 16.7 +/- 5.8 and 30.9 +/- 10.2 mmHg, respectively. Isovolumetric relaxation time (IVRT) and left atrial reservoir strain could moderately estimate PAWP (r = 0.656; P < 0.001). LVEDP was only modestly predicted by IVRT and right ventricular wall thickness (r = 0.548; P < 0.001). Surprisingly, a low correlation was found between E/e'mean and PAWP (r = 0.240; P = 0.019), E/e'mean and LVEDP (r = 0.081; P = 0.453). Correlation coefficients were similar in patients with and without atrial fibrillation. CONCLUSION: In patients with HFpEF, echocardiographic measurements, including the E/e' ratio, have a poor to moderate predictive value for the estimation of invasively acquired LVEDP and PAWP. This limitation should be taken into account for the diagnosis and evaluation of patients with HFpEF. PMID- 28984058 TI - Multivariate analysis of risk factors for cisplatin-induced nephrotoxicity in gynecological cancer. AB - AIM: Risk factors for cisplatin-induced nephrotoxicity (CIN) vary by population. This study aimed to assess risk factors for CIN in patients with gynecological cancer. METHODS: Patients who underwent cisplatin-based chemotherapy for gynecological cancer between January 2009 and December 2015 at Aichi Medical University School of Medicine were included in this study. CIN was defined according to the 'risk, injury, failure, loss, and end-stage kidney disease' (RIFLE) criteria and classified as either risk (Class R) or injury (Class I). Analyses were performed using univariate and multivariate logistic regression models. RESULTS: Among 112 patients enrolled, 30 had CIN. Multivariate analysis revealed that hydration with magnesium (odds ratio [OR], 0.223), history of cisplatin use (OR, 4.420), and hypoalbuminemia (OR, 4.170) were risk factors for Class R, and that frequency of cisplatin administration (OR, 5.620) and hydration with magnesium (OR, 0.216) were risk factors for Class I. CONCLUSION: This study confirmed that hydration without magnesium, history of cisplatin use, frequency of cisplatin administration, and hypoalbuminemia are significant risk factors for CIN. PMID- 28984059 TI - Treatment of hepatitis C with 8 weeks of ledipasvir/sofosbuvir: Highly effective in a predominantly black male patient population. PMID- 28984061 TI - Management of patients with cardiogenic shock on temporary mechanical circulatory support: urgent transplantation or on to the next pump? PMID- 28984055 TI - Daily cannabis and reduced risk of steatosis in human immunodeficiency virus and hepatitis C virus-co-infected patients (ANRS CO13-HEPAVIH). AB - Liver steatosis is common in human immunodeficiency virus (HIV)-hepatitis C virus (HCV)-co-infected patients. Some recent studies have found that cannabis use is negatively associated with insulin resistance in the general population and in HIV-HCV-co-infected patients. Given the causal link between insulin resistance and steatosis, we hypothesized that cannabis use has a positive impact on steatosis. Therefore, we aimed to study whether cannabis use in this population was associated with a reduced risk of steatosis, measured by ultrasound examination. ANRS CO13-HEPAVIH is a French nationwide multicentre cohort of HIV HCV-co-infected patients. Medical and socio-behavioural data from clinical follow up visits and annual self-administered questionnaires were prospectively collected. A cross-sectional analysis was conducted using data from the first visit where both ultrasound examination data for steatosis (positive or negative diagnosis) and data on cannabis use were available. A logistic regression model was used to evaluate the association between cannabis use and steatosis. Among study sample patients (n = 838), 40.1% had steatosis. Fourteen per cent reported daily cannabis use, 11.7% regular use and 74.7% no use or occasional use ("never or sometimes"). Daily cannabis use was independently associated with a reduced prevalence of steatosis (adjusted odds ratio [95% CI] = 0.64 [0.42;0.99]; P = .046), after adjusting for body mass index, hazardous alcohol consumption and current or lifetime use of lamivudine/zidovudine. Daily cannabis use may be a protective factor against steatosis in HIV-HCV-co-infected patients. These findings confirm the need for a clinical evaluation of cannabis-based pharmacotherapies in this population. Eudract.ema.europa.eu number, DGS050367. PMID- 28984060 TI - A practical approach to the management of nocturia. AB - AIM: To raise awareness on nocturia disease burden and to provide simplified aetiologic evaluation and related treatment pathways. METHODS: A multidisciplinary group of nocturia experts developed practical advice and recommendations based on the best available evidence supplemented by their own experiences. RESULTS: Nocturia is defined as the need to void >=1 time during the sleeping period of the night. Clinically relevant nocturia (>=2 voids per night) affects 2%-18% of those aged 20-40 years, rising to 28%-62% for those aged 70-80 years. Consequences include the following: lowered quality of life; falls and fractures; reduced work productivity; depression; and increased mortality. Nocturia-related hip fractures alone cost approximately ?1 billion in the EU and $1.5 billion in the USA in 2014. The pathophysiology of nocturia is multifactorial and typically related to polyuria (either global or nocturnal), reduced bladder capacity or increased fluid intake. Accurate assessment is predicated on frequency-volume charts combined with a detailed patient history, medicine review and physical examination. Optimal treatment should focus on the underlying cause(s), with lifestyle modifications (eg, reducing evening fluid intake) being the first intervention. For patients with sustained bother, medical therapies should be introduced; low-dose, gender-specific desmopressin has proven effective in nocturia due to idiopathic nocturnal polyuria. The timing of diuretics is an important consideration, and they should be taken mid-late afternoon, dependent on the specific serum half-life. Patients not responding to these basic treatments should be referred for specialist management. CONCLUSIONS: The cause(s) of nocturia should be first evaluated in all patients. Afterwards, the underlying pathophysiology should be treated specifically, alone with lifestyle interventions or in combination with drugs or (prostate) surgery. PMID- 28984063 TI - In situ and in vitro evaluation of crude protein degradation and utilisable crude protein content of barley, rye and triticale grains for ruminants. AB - Rations for dairy cows are comprised of high proportions of cereal grains. Thus, despite their low crude protein (CP) content, grains can contribute considerably to the CP intake of dairy cows. This study was conducted to describe and compare ruminal CP degradation of a broad range of barley, rye and triticale genotypes in situ and in vitro and different methods to estimate the utilisable CP at the duodenum (uCP). Twenty samples each of rye, barley and triticale were incubated in situ and in vitro. Exponential regression analyses were used to estimate in situ degradation parameters. Further, the effective degradability (ED), ruminal undegraded CP (UDP) and uCP for ruminal passage rates of 5% and 8% per hr were estimated. The uCP was estimated in vitro and based on two different approaches using in situ UDP data and estimates of microbial synthesised protein (based on fermented organic matter [fOM] or equations of the Gesellschaft fur Ernahrungsphysiologie). The degradation rate declined from rye (43% per hr) to triticale (27% per hr) to barley (20% per hr), and it exhibited remarkable variation between the genotypes of a single species. The maximal degradable CP fraction also differed between the species, but was overall very high (94%-99%). The lowest washout fraction (26%) and the highest variation in ED (77%-86% and 69%-80% for a passage rate of 5% and 8% per hr, respectively) were found in barley. The in situ uCP content (estimated using fOM) was lower for barley than for rye and triticale at ruminal passage rates of 5% and 8% per hr (barley: 157 g/kg DM at both passage rates; rye and triticale: 168 (at 5% per hr) and 169 (at 8% per hr) g/kg DM). In vitro estimations of uCP did not differ between the grain species and uCP estimated according to GfE was higher for triticale than for barley and rye, which did not differ. The low variation within a single grain species and the weak correlations between ruminal CP degradation and nutrient concentrations suggested that differentiation of ED and uCP between the genotypes of a single grain species is not necessary. PMID- 28984065 TI - In vitro study of stimulation effect on endothelialization by a copper bearing cobalt alloy. AB - Endothelialization is an important process after stenting in coronary artery. Recovery of the injured site timely can reduce the neointima formation and platelet absorbance, leading to a lower risk of in-stent restenosis. Copper is known to be critical in vascular construction. Thus a combination of copper with stent materials is a meaningful attempt. A copper bearing L605-Cu cobalt alloy was prepared and its effect on human umbilical vein endothelial cells (HUVECs) was evaluated in vitro in this study. It was found that HUVECs attached and stretched better on the surface of L605-Cu compared with L605, and the apoptosis of cells was decreased simultaneously. The migration and tube formation of HUVECs were also enhanced by the extract of L605-Cu. Furthermore, L605-Cu increased the mRNA expression of VEGF in HUVECs significantly. However it had no effect on the secretion of NO or mRNA expression of eNOS. The result of blood clotting test indicated that L605-Cu had better blood compatibility. These results above have demonstrated that the L605-Cu alloy is promising to be a new stent material with function of accelerating endothelialization. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 561-569, 2018. PMID- 28984064 TI - Loss of SIRT2 leads to axonal degeneration and locomotor disability associated with redox and energy imbalance. AB - Sirtuin 2 (SIRT2) is a member of a family of NAD+ -dependent histone deacetylases (HDAC) that play diverse roles in cellular metabolism and especially for aging process. SIRT2 is located in the nucleus, cytoplasm, and mitochondria, is highly expressed in the central nervous system (CNS), and has been reported to regulate a variety of processes including oxidative stress, genome integrity, and myelination. However, little is known about the role of SIRT2 in the nervous system specifically during aging. Here, we show that middle-aged, 13-month-old mice lacking SIRT2 exhibit locomotor dysfunction due to axonal degeneration, which was not present in young SIRT2 mice. In addition, these Sirt2-/- mice exhibit mitochondrial depletion resulting in energy failure, and redox dyshomeostasis. Our results provide a novel link between SIRT2 and physiological aging impacting the axonal compartment of the central nervous system, while supporting a major role for SIRT2 in orchestrating its metabolic regulation. This underscores the value of SIRT2 as a therapeutic target in the most prevalent neurodegenerative diseases that undergo with axonal degeneration associated with redox and energetic dyshomeostasis. PMID- 28984066 TI - Nanostructured fumarate copolymer-chitosan crosslinked scaffold: An in vitro osteochondrogenesis regeneration study. AB - In the tissue engineering field, the design of the scaffold inspired on the natural occurring tissue is of vital importance. Ideally, the scaffold surface must promote cell growth and differentiation, while promote angiogenesis in the in vivo implant of the scaffold. On the other hand, the material selection must be biocompatible and the degradation times should meet tissue reparation times. In the present work, we developed a nanofibrous scaffold based on chitosan crosslinked with diisopropylfumarate-vinyl acetate copolymer using anodized aluminum oxide (AAO) templates. We have previously demonstrated its biocompatibility properties with low cytotoxicity and proper degradation times. Now, we extended our studies to demonstrate that it can be successfully nanostructured using the AAO templates methodology, obtaining a nanorod-like scaffold with a diameter comparable to those of collagen fibers of the bone matrix (170 and 300 nm). The nanorods obtained presented a very homogeneous pattern in diameter and length, and supports cell attachment and growth. We also found that both osteoblastic and chondroblastic matrix production were promoted on bone marrow progenitor cells and primary condrocytes growing on the scaffolds, respectively. In addition, the nanostructured scaffold presented no cytotoxicity as it was evaluated using a model of macrophages on culture. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 570-579, 2018. PMID- 28984067 TI - Resistance characterization of ledipasvir and velpatasvir in hepatitis C virus genotype 4. AB - HCV genotype 4 (GT4) has often been overlooked in drug development, even though it infects ~20 million people worldwide. Ledipasvir/sofosbuvir and sofosbuvir/velpatasvir were highly efficacious in GT4 HCV-infected patients from GS-US-337-1119 and GS-US-342-1138. Here, we characterize the resistance profile of ledipasvir (LDV) and velpatasvir (VEL) in patients with GT4 HCV infection. NS5A deep-sequencing was performed for 454 patients infected with HCV GT4 at baseline, including 44 patients enrolled in GS-US-337-1119 and 116 patients enrolled in GS-US-342-1138, and at relapse for patients with virologic failure. LDV and VEL susceptibilities of 56 patient isolates were determined. In GS-US-337 1119, SVR12 rates were 100% for all subtypes except 4b and 4r. Phenotypic assessment of 56 HCV NS5A patient isolates from various GT4 subtypes indicated that LDV had high potency for the common subtypes 4a/d, and subtypes 4c/f/k/l/m/n/o/p/r/t despite the presence of resistance-associated substitutions (RASs). For the rare GT4b, LDV median EC50 was higher, but with a broad range of individual values. Importantly, all GT4b isolates tested had 2-4 NS5A RASs, some including Y93H. Similarly, the 2 GT4r infected patients who had virologic relapse had rare triple RASs. Reversion of these substitutions to the consensus residue significantly increased LDV susceptibility. In GS-US-342-1138, all patients achieved SVR12, regardless of their subtype or presence of RASs. In vitro data confirmed that VEL is potent against all GT4 isolates tested. LDV and VEL are potent antiviral drugs, estimated to be effective against >95% and >99%, respectively, of GT4 HCV isolates. PMID- 28984068 TI - Dental visiting behaviours among primary schoolchildren: Application of the health belief model. AB - OBJECTIVES: This study aimed to develop and validate a new instrument based on the health belief model and to use the instrument to investigate the determinants of regular dental attendance among primary schoolchildren. METHODS: A cross sectional study was conducted using a newly developed measurement scale based on the HBM, 4 health-promoting schools participated in the study and 958 students studying in grades 4-6 completed the questionnaire. The psychometric properties of the instrument were analysed, and a path analysis model was used to identify the determinants of regular dental attendance. RESULTS: The instrument had good internal consistency (Cronbach's alpha = 0.826-0.925) and a factor structure identical to HBM. Overall, the schoolchildren's health beliefs on caries treatment were positive. The determinants of regular dental visit were school location (beta = -0.13), mother's education level (beta = 0.15), susceptibility (beta = -0.18) and barriers (beta = -0.11). CONCLUSION: This study provided evidence that HBM is applicable to children's dental visiting behaviour and their health beliefs towards adherence to caries treatment. Although children had a positive attitude towards dental visits, environmental obstacles would interfere with dental visits. The newly developed instrument could be used to identify high risk children and help design oral health interventions for these children. Moreover, policy makers should increase the accessibility of dental resources to enhance the utilization of dental care among schoolchildren. PMID- 28984069 TI - Assessment of radiopharmaceutical retention for vascular access ports using positron emission tomography imaging. AB - PURPOSE: The purpose of this study was to resolve the issue of whether various generations of CR Bard peripheral vascular access ports and catheters are prone to retain PET radiopharmaceuticals. The study evaluates the residual radioactivity remaining following injection for two PET radiopharmaceuticals currently used extensively in the clinic, FDG and Na18 F. METHODS: FDG was purchased from a local cyclotron facility and Na18 F was prepared in-house. Three generations of currently marketed vascular access ports were tested. A total of five (n = 5) of each model was tested. Radiopharmaceutical of 2-3 mCi of each was injected into each port and flushed with 10, 30, 60, and 120 ml of saline. MicroPET scans were performed after each flush to detect the residual radioactivity on each port. A dose calibrator was used to detect the retention of radioactivity after each flush. RESULTS: Radioactivity retention for all vascular port models measured by microPET imaging was similar for both FDG and Na18 F, with less than 1% residual activity following a 10 ml saline flush. Based on the microPET images, all the subsequent flushes of 30, 60, and 120 ml were also considered. Dose calibrator activity measurements validated microPET measurements as negligible for all the ports, even with the first 10 ml flush. CONCLUSIONS: MicroPET imaging was more sensitive than the dose calibrator in determining the radioactivity retention of the vascular access ports from CR Bard. These ports may be used for the injection of FDG and Na18 F to track glucose metabolism and bone uptake with PET imaging. It is recommended to apply at least a 10 ml flush after radiopharmaceutical administration, to reduce residual activity to baseline levels. PMID- 28984070 TI - Reducing harms: Focus on drug-drug interactions and adverse drug events. PMID- 28984071 TI - Type 2 diabetes: Does pancreatic fat really matter? AB - With the increasing prevalence of obesity, the interest of research in nonalcoholic fatty pancreas disease (NAFPD) has grown. Even though the pancreas appears more susceptible to lipid accumulation compared with the liver, NAFPD has been less investigated due to the limits in detecting techniques. Several definitions and synonyms for NAFPD are used by authors and can be misleading. This, together with differences in methodology and ethnicity, make the integration and comparison of studies on this topic challenging. NAFPD could be used as an early indicator of ectopic fat deposition, which is recognized as a key factor of obesity cardio-metabolic complications. However, evidence that NAFPD has a pathogenetic role in type 2 diabetes is also emerging. This article reviews the current state of knowledge on the clinical and pathophysiologic relevance of NAFPD in beta-cell function and insulin resistance. PMID- 28984073 TI - Which aspects of mindfulness are important to include in adolescent interventions? AB - AIM: Despite widespread enthusiasm to adopt universal mindfulness-based interventions (MBIs) for youth, high-quality evidence is still lacking. It remains unknown how best to modify the successful adult curricula to render them accessible for young people but still effective. Specifically, it is unclear whether particular elements of mindfulness are key ingredients. The aim of this research was to identify the relation between aspects of baseline mindfulness and longitudinal trajectories related to well-being in adolescence. METHOD: We examined associations between eight aspects of mindfulness at baseline and longitudinal trajectories of depression, anxiety, well-being, weight concern and shape concern over a 12-month period in early adolescents (N = 499; 46% female; Mage at baseline 13.45 years; SD = .33). RESULTS: We found a transdiagnostic protective effect for those high in Accepting and Nonjudgmental Orientation, Decentering and Nonreactivity and Acting with Awareness, with effect sizes across the variables ranging from small to large (Cohen's d = .29-1.26) although this benefit reduced over time, especially for weight and shape concerns in girls. CONCLUSION: This natural but waning protective effect strengthens the case for MBIs in youth. The isolation of three key elements is an important preliminary step in identifying ways to improve the effectiveness of current adolescent curricula. Of the three, the current study suggests that teaching young adolescents to respond to their mistakes with kindness and non-judgement should be a prime focus. PMID- 28984072 TI - Recruiting a representative sample in adherence research-The MALT multisite prospective cohort study experience. AB - Medication adherence is an important determinant of transplant outcomes. Attempts to investigate adherence are frequently undermined by selection bias: It is very hard to recruit and retain non-adherent patients in research efforts. This manuscript presents recruitment strategies and results from the MALT (Medication Adherence in children who had a Liver Transplant) multisite prospective cohort study. MALT sites recruited 400 pediatric liver transplant patients who agreed to be followed for 2 years. The primary purpose was to determine whether a marker of adherence, the Medication Level Variability Index (MLVI), predicts rejection outcomes. The present manuscript describes methods used in MALT to ensure that a representative sample was recruited, and presents detailed recruitment results. MALT sites were able to recruit a nationally representative sample, as determined by a comparison between the MALT cohort and a national sample of transplant recipients. Strategies that helped ensure that the sample was representative included monitoring of the outcome measure in comparison with a national sample, drastically limiting patient burden, and specific recruitment methods. We discuss the importance of a representative sample in adherence research and recommend that future efforts to study adherence pay special attention to sample characteristics. PMID- 28984074 TI - Availability of comprehensive services in permanent supportive housing in Los Angeles. AB - Studies have often described a specific model or models of permanent supportive housing (PSH), yet few studies have systematically examined what services are typically offered to PSH tenants in any given service system and how those services are offered. Using telephone surveys from 23 PSH agency supervisors and qualitative data collected from 11 focus groups with 60 frontline providers and 17 individual interviews with supervisors from a subset of surveyed agencies-all of which were completed between July 2014 and December 2015-the goal of this study is to better understand what services are being offered in PSH organisations located in Los Angeles and what barriers frontline providers face in delivering these services. Survey findings using statistical frequencies suggest the existence of robust support services for a high-needs population and that single-site providers may offer more services than scatter-site providers. Qualitative thematic analysis of interview and focus group transcripts suggests services may be less comprehensive than they appear. If PSH is to be regarded as an intervention capable of more than "just" ending homelessness, further consideration of the provision of supportive services is needed. PMID- 28984075 TI - Association of glucocorticoid receptor gene polymorphisms with systemic lupus erythematosus in a Chinese population. AB - OBJECTIVES: To identify the association of glucocorticoid receptor (GR) gene polymorphism with systemic lupus erythematosus (SLE). METHODS: A case-control study was carried out, in which 400 Chinese patients with SLE and 400 normal people were enrolled. DNA was extracted using a genomic DNA extraction kit, and tagged single nucleotide polymorphisms (SNPs) were identified by Haploview (4.0) Project from the Chinese HapMap Project. Eighteen tagged SNPs of the GR gene were genotyped by the Multiplex SNaPshot technique. RESULTS: Two GR gene SNPs were associated with the pathogenesis of SLE: rs6865292 (dominant model: crude odds ratio [OR] = 1.526, 95% CI: 1.151-2.025, P = 0.003; adjusted OR = 1.525, 95% CI: 1.149-2.023, P = 0.004; PBH = 0.036) and rs9324921 (dominant model: crude OR = 1.556, 95% CI: 1.173-2.062, P = 0.002; adjusted OR = 1.553, 95% CI: 1.171-2.060, P = 0.002; PBH = 0.036). The haplotype analysis of GR gene SNPs manifested that the haplotype of 'CCGGG' (OR = 2.701, 95% CI: 1.348-5.410, P = 0.004; PBH = 0.036) was a risk factor for the development of SLE. A lower frequency of A allele of SNP rs4607376 (P = 0.021; OR = 0.794, 95% CI: 0.652-0.966, PBH = 0.126), higher frequency of C-allele of SNP rs6865292 (P = 0.019, OR = 1.317, PBH = 0.126) and A-allele of SNP rs9324921 (P = 0.019, OR = 1.317, PBH = 0.126) may be risk factors for developing SLE. The rs7719514 (recessive model: crude P = 0.044; adjusted P = 0.044, PBH = 0.264), rs7701443 (recessive model: crude P = 0.044, adjusted P = 0.045; PBH = 0.264), rs4607376 (recessive model: crude P = 0.027; adjusted P = 0.026; PBH = 0.264) and haplotype 'CAGCG' (P = 0.044; PBH = 0.198) showed marginal association with the pathogenesis of SLE. In the case group, there were no significant differences between non-lupus nephritis and lupus nephritis. Further, we found that the SNP rs12054797 (F = 3.228, P = 0.041, PBH = 0.342), rs2963156 (F = 3.163, P = 0.043, PBH = 0.342) might be marginally associated with disease activity. CONCLUSIONS: The study indicates that GR genetic polymorphisms may play a major role in the pathogenesis and development of SLE. PMID- 28984077 TI - Broad clinical high-risk mental state (CHARMS): Methodology of a cohort study validating criteria for pluripotent risk. AB - AIM: The development of the ultra-high risk (UHR) criteria for psychosis created a new paradigm for the prevention research in psychiatry. Since (1) prevention research faces the challenge of achieving adequate statistical power when focusing on single low-incidence syndromes and (2) early clinical phenotypes are overlapping and non-specific, this study broadens the UHR state beyond psychosis as an outcome. The CHARMS (clinical high at-risk mental state) study aims to prospectively validate a set of trans-diagnostic criteria to identify help seeking young people at risk of developing a range of serious mental illnesses. METHODS: This paper describes the methodology of the CHARMS study, which involves applying the CHARMS criteria to a cohort of help-seeking young people aged 12 to 25 attending youth mental health services in Melbourne. New referrals meeting the CHARMS criteria are allocated to the CHARMS+ group; referrals not meeting CHARMS threshold are allocated to CHARMS- group (control group); referrals meeting criteria for a full-threshold disorder are excluded. Transition status and clinical and functional outcomes are re-assessed at 6 and 12 months. CONCLUSIONS: This study will be the first to introduce and validate clinical criteria to identify a broader at-risk patient population, which may facilitate young people's access to clinical services and early treatment by reducing the reliance on "caseness" defined according to current diagnostic categories being required for service entry. These criteria may introduce a new, trans-diagnostic approach for understanding risk factors and pathogenic mechanisms that drive the onset of severe mental illness and the next generation of preventive intervention trials. PMID- 28984076 TI - Patterns of Eating Disorder Pathology are Associated with Weight Change in Family Based Behavioral Obesity Treatment. AB - OBJECTIVE: Children with overweight or obesity have elevated eating disorder (ED) pathology, which may increase their risk for clinical EDs. The current study identified patterns of ED pathology in children with overweight or obesity entering family-based behavioral weight loss treatment (FBT) and examined whether children with distinct patterns differed in their ED pathology and BMI z score (zBMI) change across FBT. METHODS: Before participating in a 16-session FBT, children (N = 241) completed surveys or interviews assessing ED pathology (emotional eating, shape/weight/eating concerns, restraint, and loss of control [LOC]). Shape and weight concerns (SWC) and LOC were also assessed post treatment. Child height and weight were measured at baseline and post treatment. Latent class analysis identified patterns of ED pathology. Repeated-measures ANOVA examined changes in zBMI and ED pathology. RESULTS: Four patterns of ED pathology were identified: low ED pathology, SWC, only loss of control, and high ED pathology. SWC decreased across treatment, with the highest decreases in patterns characterized by high SWC. All groups experienced significant decreases in zBMI; however, children with the highest ED pathology did not achieve clinically significant weight loss. CONCLUSIONS: ED pathology decreased after FBT, decreasing ED risk. While all children achieved zBMI reductions, further research is needed to enhance outcomes for children with high ED pathology. PMID- 28984078 TI - Controlling Non-Equilibrium Structure Formation on the Nanoscale. AB - Controlling the structure formation of gold nanoparticle aggregates is a promising approach towards novel applications in many fields, ranging from (bio)sensing to (bio)imaging to medical diagnostics and therapeutics. To steer structure formation, the DNA-DNA interactions of DNA strands that are coated on the surface of the particles have become a valuable tool to achieve precise control over the interparticle potentials. In equilibrium approaches, this technique is commonly used to study particle crystallization and ligand binding. However, regulating the structural growth processes from the nano- to the micro- and mesoscale remains elusive. Here, we show that the non-equilibrium structure formation of gold nanoparticles can be stirred in a binary heterocoagulation process to generate nanoparticle clusters of different sizes. The gold nanoparticles are coated with sticky single stranded DNA and mixed at different stoichiometries and sizes. This not only allows for structural control but also yields access to the optical properties of the nanoparticle suspensions. As a result, we were able to reliably control the kinetic structure formation process to produce cluster sizes between tens of nanometers up to micrometers. Consequently, the intricate optical properties of the gold nanoparticles could be utilized to control the maximum of the nanoparticle suspension extinction spectra between 525 nm and 600 nm. PMID- 28984079 TI - Two-dimensional and three-dimensional models for studying atherosclerosis pathogenesis induced by periodontopathogenic microorganisms. AB - Epidemiological studies have established a clinical association between periodontal disease and atherosclerosis. Bacteremia and endotoxemia episodes in patients with periodontitis appear to link these two diseases by inducing a body wide production of cardiovascular markers. The presence of oral bacteria in atherosclerotic lesions in patients with periodontitis suggests that bacteria, or their antigenic components, induce alterations in the endothelium associated with atherosclerosis. Therefore, a causal mechanism explaining the association between both diseases can be constructed using in vitro models. This review presents current experimental approaches based on in vitro cell models used to shed light on the mechanism by which periodontal pathogenic microorganisms, and their antigenic components, induce proatherosclerotic endothelial activity. Monolayer cultures of endothelial vascular or arterial cells have been used to assess periodontal pathogenic bacteria and their antigenic compounds and endothelial activation. However, these models are not capable of reflecting the physiological characteristics of the endothelium inside vascularized tissue. Therefore, the shift from two-dimensional (2D) cellular models toward three-dimensional (3D) models of endothelial cells resembling an environment close to the physiological environment of the endothelial cell within the endothelium is useful for evaluating the physiological relevance of results regarding the endothelial dysfunction induced by periodontopathogens that are currently obtained from 2D models. The use of in vitro 3D cellular models can also be relevant to the search for therapeutic agents for chronic inflammatory diseases such as atherosclerosis. Here, we present some strategies for the assembly of 3D cultures with endothelial cells, which is useful for the study of periodontopathogen-mediated disease. PMID- 28984080 TI - Inhibitory effect of GMI, an immunomodulatory protein from Ganoderma microsporum, on myofibroblast activity and proinflammatory cytokines in human fibrotic buccal mucosal fibroblasts. AB - Oral submucous fibrosis (OSF) has been indicated as one of the oral potentially malignant disorders. Epidemiological studies have attributed this pathological fibrosis to the habit of areca nuts chewing, which causes chronic inflammation and persistent activation of myofibroblasts in the oral cavity. Hence, it is crucial to find an effective intervention to ameliorate inflammation in order to prevent the malignant progression of OSF. In this study, we assessed the anti inflammatory effect of the immunomodulatory protein, GMI, extracted from Ganoderma microsporum on the expression proinflammatory cytokines and the myofibroblast characteristics in human fibrotic buccal mucosal fibroblasts (fBMFs). Our results demonstrated that the expression level of interleukin (IL)-6 and IL-8 were decreased after exposure of GMI and the myofibroblast activities, including collagen gel contraction, migration, invasion, and wound healing abilities were inhibited as well. Furthermore, we confirmed these findings in the arecoline-stimulated BMFs. Consistent with the above findings, the expression of the myofibroblast marker alpha-smooth muscle actin and other fibrogenic markers, such as type I collagen, fibronectin, and vimentin in fBMFs were all reduced in a dose-dependent manner. Collectively, our data suggested that GMI suppressed the proinflammatory cytokines and myofibroblast features in fBMFs, and could serve as a promising and natural antifibrosis agent. PMID- 28984081 TI - One pot synthesis of new poly(vinyl alcohol) blended natural polymer based magnetic hydrogel beads: Controlled natural anticancer alkaloid delivery system. AB - Facile one-pot synthesis has been demonstrated for new biocompatible and dual responsive magnetic iron oxide nanoparticles cross-linked poly(vinyl alcohol) (PVA) blended natural polymer chitosan (CS) based hydrogel beads (mCS-PVA) as a controlled natural anticancer alkaloid Luotonin A (LuA) delivery system. The prepared magnetic hydrogel beads were characterized using powder X-ray diffraction measurement, Fourier transform-infrared spectroscopy, scanning electron microscopy, energy dispersive X-ray spectroscopy, and vibrating sample magnetometer. The magnetic hydrogel beads are exhibited significant water retention and follow the second order kinetic model in swelling study. The swelling ratio of the magnetic gel beads increased by the addition of PVA and showed a maximum swelling ratio of 40.83 +/- 1.01 g/g and follows non-Fickian water transport mechanism. Stimuli responsive mCS and mCS-PVA hydrogel beads functionalized with LuA is demonstrated for controlled release at physiological pH and under magnetic field. The magnetic hydrogel beads show highest LuA releasing efficacy at acidic medium (pH = 5.0) with maximum efficiency of 73.33 +/- 1.44%. This efficacy may also be tuned by altering the external magnetic field as well as the weight percentage (wt %) of polyethylene glycol. It is clearly that the newly produced magnetic hydrogel beads can be served as an effective intestinal LuA delivery system. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 543-551, 2018. PMID- 28984082 TI - Performance evaluation of the microINR(r) point-of-care INR-testing system. AB - INTRODUCTION: Point-of-care International Normalised Ratio (INR) testing is used frequently. We evaluated the microINR(r) POC system for accuracy, precision and measurement repeatability, and investigated instrument and test chip variability and error rates. METHODS: Venous blood INRs of 210 patients on warfarin were obtained with Thromborel(r) S on the Sysmex CS-2100i(r) analyser and compared with capillary blood microINR(r) values. Precision was assessed using control materials. Measurement repeatability was calculated on 51 duplicate finger-prick INRs. Triplicate finger-prick INRs using three different instruments (30 patients) and three different test chip lots (29 patients) were used to evaluate instrument and test chip variability. RESULTS: Linear regression analysis of microINR(r) and Sysmex CS2100i(r) values showed a correlation coefficient of 0.96 (P < .0001) and a positive proportional bias of 4.4%. Dosage concordance was 93.8% and clinical agreement 95.7%. All acceptance criteria based on ISO standard 17593:2007 system accuracy requirements were met. Control material coefficients of variation (CV) varied from 6.2% to 16.7%. The capillary blood measurement repeatability CV was 7.5%. No significant instrument (P = .93) or test chip (P = .81) variability was found, and the error rate was low (2.8%). CONCLUSION: The microINR(r) instrument is accurate and precise for monitoring warfarin therapy. PMID- 28984083 TI - Temporal trends in Giardia occurrence in the Grand River and surrounding tributaries, Waterloo, Ontario (2005-2013), a retrospective analysis of surveillance data. AB - Giardia contamination in the Grand River Watershed (south-western Ontario, Canada) was monitored from 2005 to 2013 as part of FoodNet Canada. Our study objectives were to describe the temporal pattern of Giardia occurrence and determine whether water quality parameters and bacterial indicators could act as effective markers for Giardia occurrence. Water samples were collected monthly from the Grand River near a drinking water intake point (2005-2013) and also collected intermittently from other areas in the watershed during the study period. Samples were tested for Giardia cysts using the US EPA method 1623. Samples were also tested for chemical and microbial water quality indicators. Univariable and multivariable linear regression models were built to examine whether temporal, water quality and bacterial indicators were associated with Giardia cyst concentration. Giardia cysts were identified in 89% of samples (n = 228), with highest measured concentrations downstream of a waste water treatment plant outfall. Year and season were found to be predictors for Giardia occurrence. Concentrations were significantly higher in the winter and fall compared to the summer, and significantly higher in 2007 compared to other study years. After controlling for season, year and sampling location, dissolved oxygen was the only variable significantly associated with Giardia cyst concentration. Seasonal peaks in Giardia cyst concentrations in samples collected near the intake for the drinking water plant did not align with the seasonal peak in human Giardiasis cases in this region that are reported annually by public health authorities. This suggests that the risk of contracting Giardiasis from treated drinking water in this community is possibly low when the treatment plant is functioning adequately. Instead, waterborne exposure is likely the result of seasonal behaviours surrounding recreational water use. Therefore, the collective findings of our study are important to help inform future risk management studies and guide public health protection policies. PMID- 28984084 TI - Relevance of sample preparation for flow cytometry. AB - INTRODUCTION: Flow cytometry is a useful tool for diagnosis and minimal residual disease (MRD) study of hematological diseases. Standard sample preparation protocols are characterized by stain-lyse-wash (SLW). To prevent nonspecific bindings and achieve high sensitivity in MRD studies, lyse-wash-stain-wash (LWSW) is required. To our knowledge, no comparison between the two methods has been performed. METHODS: We compared mean fluorescence intensity (MFI), stain index, signal-to-noise ratio, and percentage of positive cells of 104 antibodies and of 13 selected antibodies tested in 10 samples simultaneously prepared with the two methods. RESULTS: MFI and percentages of positive cells obtained by the two methods did not show significant differences and showed a very high correlation. Stain index and signal-to-noise ratio presented higher values for kappa and lambda surface chains in LWSW samples and a trend of higher values for the other antibodies in SLW samples. CONCLUSIONS: We suggest to use LWSW method also at diagnosis to obtain more comparable antibody intensity expressions when samples from the same patient are processed for MRD evaluation after bulk lysis. Moreover, LWSW can prevent nonspecific bindings, shows no differences in the identification and quantitation of the populations of interest, and reduces acquisition of cell debris. PMID- 28984085 TI - Immunoprotective effects of a hemin-binding peptide derived from hemagglutinin-2 against infection with Porphyromonas gingivalis. AB - The principal etiologic agent in periodontal disease, Porphyromonas gingivalis, generates cysteine proteases that bind heme with domains such as hemagglutinin-2 (HA2). High-affinity HA2-hemin binding supplies the porphyrin and ferric iron needed for growth and virulence. The DHYAVMISK peptide, recently identified at the hemin-binding site of HA2, inhibits hemin binding. We now evaluate the protective effect of vaccination with DGFPGDHYAVMISK (termed DK) against P. gingivalis using a rat infection model. Rats immunized with DK generated anti peptide serum IgGs and salivary sIgAs (as measured by ELISA). In a subcutaneous abscess model, the protective effect of immunization was then investigated by measuring abscess size following subcutaneous injection with P. gingivalis. In an oral infection model, a ligature inoculated with P. gingivalis was used to induce periodontitis. The degree of bone erosion, ordinarily provoked by infection, was then evaluated by micro-computed tomography. We found that anti-peptide antibody titers of serum IgGs and salivary sIgAs for rats immunized with DK and adjuvant were significantly higher than for sham-immunized rats (injected with adjuvant/PBS alone; P < .05). In the subcutaneous abscess model, the DK + adjuvant-vaccinated rats recovered faster than sham-vaccinated animals, with their abscess sizes significantly smaller (P < .05). Further, in the experimental periodontitis model, bone loss at the molar palatal side for DK + adjuvant vaccinated rats was significantly lower than for sham-vaccinated animals (P < .05). Collectively, these data demonstrate the potential of (DK) peptide immunization in terms of eliciting an immunoprotective effect against infection with P. gingivalis. PMID- 28984086 TI - Catalytic Hydrogenation of Macroalgae-Derived Alginic Acid into Sugar Alcohols. AB - Alginic acid, a major constituent of macroalgae, iss hydrogenated into sugar alcohols over carbon-supported noble metals for the first time. Mannitol and sorbitol are the major products of the catalytic hydrogenation of alginic acid, which consists of two epimeric uronic acids. The main reaction pathway is the consecutive hydrogenations of the aldehyde and carboxyl ends of alginic acid dimers, followed by the cleavage of the C-O-C linkage into monomeric units by hydrolysis. The highest yield of C6 sugar alcohols is 61 % (sorbitol: 29 %; mannitol: 28 %; galactitol: 4 %). The low sorbitol/mannitol ratio is in contrast to that from cellulose hydrogenation, owing to the composition of alginic acid and isomerization between sugar alcohols under the catalytic system. This new green route to producing sugar alcohols from alginic acid might provide opportunities to diversify biomass resources. PMID- 28984088 TI - Label-free nanoscale characterization of red blood cell structure and dynamics using single-shot transport of intensity equation. AB - We report the results of characterization of red blood cell (RBC) structure and its dynamics with nanometric sensitivity using transport of intensity equation microscopy (TIEM). Conventional transport of intensity technique requires three intensity images and hence is not suitable for studying real-time dynamics of live biological samples. However, assuming the sample to be homogeneous, phase retrieval using transport of intensity equation has been demonstrated with single defocused measurement with x-rays. We adopt this technique for quantitative phase light microscopy of homogenous cells like RBCs. The main merits of this technique are its simplicity, cost-effectiveness, and ease of implementation on a conventional microscope. The phase information can be easily merged with regular bright-field and fluorescence images to provide multidimensional (three dimensional spatial and temporal) information without any extra complexity in the setup. The phase measurement from the TIEM has been characterized using polymeric microbeads and the noise stability of the system has been analyzed. We explore the structure and real-time dynamics of RBCs and the subdomain membrane fluctuations using this technique. PMID- 28984089 TI - Airway management with Fastrach laryngeal mask versus Spritztube: a prospective randomized manikin-based study. AB - BACKGROUND: A new promising device, the Spritztube (ST), was developed combining the ability to perform both supraglottic ventilation and orotracheal fibreoptic intubation using the same device, allowing an easy passage from supraglottic ventilation to tracheal ventilation avoiding apnea. The present study aims to compare the speed and the subjective ease of insertion of the novel tracheal tube (Spritztube(r)) compared to the intubating laryngeal mask airway FastrachTM (FT LMA) in a simulation environment. METHODS: Each participant received verbal instruction and practical demonstration concerning "technique of insertion" for both devices on manikin and, in a randomized order, used both devices. Time of placement (T1), time of inflation (T2), the elapsed procedural time (T3), ease of insertion, time of exchange maneuver for intubation (T4), success rates and number of attempts were recorded for each EAD. RESULTS: Forty-seven participants were enrolled. The ST was judged as easier insertion than FT-LMA (P<0.001) having also a significant higher success rate than FT-LMA (P<0.001). Number of attempts for insertion was similar. Number of attempts for exchange to ETI was significantly more for FT-LMA (P<0.001). FT-LMA was applied 11 s faster than the ST (median T3 Fastrach: 13 s, ST: 24 s, P<0.001) as the exchange maneuver for ETI (median T4 FT-LMA: 13 s, ST: 24 s, P<0.001). CONCLUSIONS: In a manikin simulation setting, insertion and intubation with and ST was performed 11 s slower than with use of a FT-LMA. PMID- 28984087 TI - Effects of Rhei Undulati Rhizoma on lipopolysaccharide-induced neuroinflammation in vitro and in vivo. AB - Neuroinflammation plays a critical role in the pathogenesis of degenerative brain diseases such as Alzheimer's disease and Parkinson's disease. Microglia are the major components of the brain immune system that regulate inflammatory processes. Activated microglia release pro-inflammatory factors and cytokines, resulting in neuronal cell death. We focused on inhibiting the activation of microglia from a stimulus as a strategy to search for neuroprotective drugs. Rhei Undulati Rhizoma (RUR) is traditionally used to treat various inflammatory disorders. In this study, we investigated whether RUR modulates inflammatory processes in lipopolysaccharide (LPS)-stimulated BV2 microglia cells and the mouse brain. RUR exerted anti-neuroinflammatory effects by inhibiting the production of nitric oxide and reactive oxygen species induced by LPS via the downregulation of transcription factors such as inducible nitric oxide synthase and cyclooxygenase 2 (COX-2) without causing cytotoxicity. RUR also regulated mitogen-activated protein kinase pathway by inhibiting phosphorylation of p38 and c-Jun N-terminal kinases and translocation of nuclear factor kappa B. Moreover, RUR attenuated LPS induced glial activation and COX-2 expression in the substantia nigra and hippocampus of the mouse brain. These results indicate that RUR is a potential candidate to treat neurodegenerative diseases by regulating neuroinflammation. PMID- 28984090 TI - Bispectral-Index-measured sevoflurane requirement might be decreased in individuals with major depressive disorder. AB - BACKGROUND: GABA (gamma-aminobutyric acid) is the primary inhibitory neurotransmitter in the CNS and well-known target for general anesthetics. In addition, the dysregulation of GABA could be involved in the etiology of major depressive disorder (MDD). In this study, we aimed to determine whether MDD has any effect on anesthetic requirement measured by Bispectral Index (BIS). METHODS: This study was designed as a prospective, observational study, registered ANZCTR (ACTRN 12616001295437), with institutional review board approval and written informed consent. Inpatients who were planned to undergo laparoscopic cholecystectomy as an elective surgery, were enrolled in this study. Patients were divided into two groups, based on the results of the Beck Depression Inventory (BDI) which was assessed the 21-item self-administered scale measuring various symptoms of depression. If the BDI score was under 10, it was accepted as control group. Patients were consulted to the psychiatrist if the BDI score was 17 or more. Patients who were diagnosed as MDD by the psychiatrist, were classified as MDD group. Anesthesia was standardized, and delivered sevoflurane concentration was adjusted according to BIS value in both groups. Parameters of the study were heart rate, non-invasive arterial blood pressure, arterial oxygen saturation, BIS, end-tidal carbon dioxide, and end-tidal concentration of sevoflurane at 5-minute intervals during the operation. RESULTS: End-tidal concentration of sevoflurane was found to be lower in MDD group during the maintenance phase of anesthesia. Mean end-tidal concentration of sevoflurane were significantly lower in MDD group (1.28+/-0.15) than control group (1.52+/-0.22) (P<0.0001). BIS values were lower at 5- and 10-minute intervals in MDD group in comparison with control group. BIS values were similar at other time intervals in both groups during surgery. CONCLUSIONS: MDD might result in decreased end-tidal concentration of sevoflurane. Further study is required to identify the relationship between MDD and anesthetics. PMID- 28984091 TI - Repeated alveolar recruitment maneuvers with and without positive end-expiratory pressure during bariatric surgery: a randomized trial. AB - BACKGROUND: Positive end-expiratory pressure (PEEP) is considered essential in protective ventilation, while it may lead to hemodynamic impairment. In the present study, we investigated the effect of repeated alveolar recruitment maneuvers (ARMs) with or without additional PEEP on the arterial oxygenation of obese patients who were undergoing bariatric surgery. METHODS: Thirty-six obese adult patients with Body Mass Index >40 kg/m2 who were scheduled for laparoscopic sleeve gastrectomy were randomly allocated into three groups: 1) control group, no intraoperative ARMs; 2) ARM+ZEEP group, repeated ARMs every 30 minutes without extra PEEP; or 3) ARM+PEEP group, ARMs followed by 8 cmH2O of PEEP from the onset of pneumoperitoneum. Arterial oxygenation, respiratory mechanics, hemodynamics, and postoperative outcomes were investigated. RESULTS: Patients in the ARM+PEEP group had significantly higher peak and plateau airway pressures during pneumoperitoneum, and more subjects required treatment with vasoconstrictors intraoperatively compared to patients in the other groups. Patients in the two ARMs treated groups had lower driving pressure during pneumoperitoneum and better arterial oxygenation in the emergence stage compared to patients in the control group. The PaO2/FiO2 ratio was 299+/-30, 315+/-39 and 245+/-43 mmHg in the ARM+ZEEP, ARM+PEEP, and control group, respectively (P<0.05 compared to control). There were no significant differences in the postoperative recovery variables between the groups. CONCLUSIONS: Repeated ARMs, either with or without PEEP, improve early postoperative oxygenation and shorten time to extubation. ARMs without PEEP result in lower airway pressure and less hemodynamic impairment in patients who were undergoing bariatric surgery. PMID- 28984092 TI - Patterns of changes in functional and neurocognitive status in elderly patients after transcatheter vs. surgical aortic valve replacements. AB - BACKGROUND: Replacement of severely stenotic aortic valve may influence cognitive and physical functioning. The aim of this study was to compare cognitive and functional status after surgical (SAVR) vs. transcatheter aortic valve replacements (TAVR) in the elderly with severe aortic stenosis (AS). METHODS: It was a prospective observational study with over 6 months of follow-up. Eighty >=70-year-old patients with AS underwent TAVR (N.=40) or SAVR (N.=40). Mini Mental State Exam (MMSE), activities daily living (ADL) score and instrumental activities daily living (IADL) score were used to assess the cognitive status, fundamental functioning and complex independent living skills, respectively. The tests were conducted at baseline and 6 months after the procedure. Additionally, MMSE was carried out at discharge. RESULTS: Baseline MMSE score was lower in the TAVR vs. SAVR group (P=0.001). In the SAVR group, there was a transient in hospital decline in mean MMSE score (P=0.020), absent in the TAVR group. Baseline ADL and IADL scores were lower in TAVR patients. Both groups experienced mild improvement. The average increase among those with improved IADL score was larger after TAVR (2.37 vs. 1.37 after SAVR; P=0.029). A systolic blood pressure (SBP) decrease <60 mmHg as well as larger periprocedural shift in SBP (expressed by a difference between maximum and minimum SBP) during TAVR were associated with the decline in the ADL (P=0.001) and IADL scores (P=0.043). CONCLUSIONS: Cognitive patterns differed between the TAVR and SAVR patients. A transient MMSE decline did not alter the 6-month status. TAVR might improve functionality. Periprocedural SBP decrease and larger changes in SBP are risk factors for functionality deterioration after TAVR. PMID- 28984093 TI - Effects of laparoscopic radical prostatectomy on intraoperative autonomic nervous system control of hemodynamics. AB - BACKGROUND: Laparoscopic radical prostatectomy induces hemodynamic changes that have been supposed due to autonomic nervous system activity. The aim of this study is to measure the sympathetic and vagal modulation on hemodynamic response to steep Trendelenburg and pneumoperitoneum for laparoscopic surgery. METHODS: Autonomic nervous system modulation was assessed noninvasively through heart rate variability and arterial pressure variability analysis in patients undergoing elective laparoscopic radical prostatectomy and in awake volunteers during head down tilt. RESULTS: Forty patients and 14 awake volunteers were studied. The induction of general anesthesia significantly decreased the heart rate, arterial pressure, vagal modulation, and sympathetic modulation. Steep Trendelenburg increased vagal and sympathetic modulation both in anesthetized and awake subjects. Pneumoperitoneum increased arterial pressure without effect on autonomic nervous system control in anesthetized patients. CONCLUSIONS: Hemodynamic changes occurring during laparoscopic radical prostatectomy reveal autonomic response to the challenges (i.e. general anesthesia and head down position), and non-neurally mediated increase of arterial pressure caused by pneumoperitoneum. This study supports the notion that during laparoscopic radical prostatectomy the association between the vagal stimulation due to Trendelenburg positioning and sympathetic withdrawal caused by general anesthesia could lead to severe bradycardia and cardiac arrest in risky patients. PMID- 28984094 TI - Mucosal and cutaneous capnometry for the assessment of tissue hypoperfusion. AB - In critically ill patients, tissue hypoperfusion is an important cause leading to multi-organ dysfunction and death, and it cannot always be detected by measuring standard global hemodynamic and oxygen-derived parameters. Gastric intramucosal partial pressure of carbon dioxide (PCO2) as measured by gastric tonometry has been recognized to be of clinical value as a prognostic factor, in assessing the effects of particular therapeutic interventions, and as an end-point of resuscitation. However, this technique has several limitations that have hampered its implementation in clinical practice. The sublingual tissue bed has been shown to be damaged in models of shock, and microcirculatory changes in this area may indicate imminent changes in other important organs. The measurement of sublingual mucosal PCO2 (PslCO2) by sublingual capnography is technically simple, noninvasive and gives near instantaneous results. Clinical studies have established that high PslCO2 values and, more especially, high PslCO2 gap (PslCO2 - arterial PCO2) values are correlated with impaired microcirculatory blood flow and a poor outcome in critically ill patients. Sublingual capnography seems to be the ideal noninvasive monitoring tool to evaluate the severity of shock states and the adequacy of tissue perfusion. However, clinical studies are needed to determine the clinical utility of PslCO2 gap monitoring as end-point target to guide resuscitation in critically ill patients. PMID- 28984095 TI - Continuous wound infusion and local infiltration analgesia for postoperative pain and rehabilitation after total hip arthroplasty. AB - BACKGROUND: Total hip arthroplasty is one of the most common procedures in orthopedic surgery. We hypothesized that local infiltration of analgesia and continuous wound infusion of anesthetics in the first 72 hours after surgery could provide more effective postoperative analgesia with better rehabilitation. METHODS: A double-blind, randomized, controlled study was conducted with 96 patients who underwent total hip arthroplasty. The patients were randomized to receive either a local infiltration analgesia and continuous wound infusion of anesthetics or a local infiltration analgesia and continuous wound infusion of saline solution. The patients in both groups received subarachnoid anesthesia and a local infiltration analgesia. A multihole catheter was placed next to the implant and connected to an electronic pump containing a 300-mL solution of 0.2% levobupivacaine (experimental group) or saline (control group). RESULTS: A total of 96 consecutive patients were enrolled and randomized. Of these, 48 patients received local infiltration analgesia and continuous wound infusion of local anesthetics, and the remainder received local infiltration analgesia and continuous wound infusion of saline solution. The analysis showed a significant main effect of treatment on the postoperative incident of pain (Ftreat(1,93)=22.62, P=0.000) and on resting pain during the post-surgery follow up (Ftreat(1,93)=15.62, P=0.0002). The pain scores during the rehabilitation period were significantly less in the experimental group. Analgesic consumption was less in the experimental group. CONCLUSIONS: The addition of continuous wound infusion of anesthetics to local infiltration analgesia provided an extended analgesic effect associated with good rehabilitation performance. PMID- 28984096 TI - Preventative effect of ketamine on post-surgical hyperalgesia induced at a body part remote from the surgical site. AB - BACKGROUND: It is known that pain hypersensitivity can be induced at a body part remote from a surgical site (tertiary hyperalgesia), leading to patient discomfort. Nevertheless, no reported study to date has investigated methods to attenuate such tertiary hyperalgesia. Ketamine is known to modulate hyperalgesia induced by central sensitization. Thus, we investigated whether intraoperative administration of ketamine could decrease post-surgical tertiary hyperalgesia in patients undergoing a laparoscopic hysterectomy. METHODS: In total 46 patients were studied. Ketamine (1 mg/kg IV and 0.5 mg/kg/h or the same volume of 0.9% saline) was administered during surgery in the ketamine and control groups, respectively. The mechanical pain threshold was measured on the patients' dominant palm before and 24 hours after the surgery to evaluate hyperalgesia. RESULTS: The change in mechanical pain threshold over time (preoperative and postoperative) differed between the groups, with a lower postoperative threshold in the control group (118.6+/-170.5 vs. 419.2+/-233; P=0.015). The postoperative visual analogue scale score at rest was lower in the ketamine group (22+/-16 vs. 13+/-9; P=0.02). Visual analogue scale scores during deep breathing, consumption of analgesia and antiemetics, and the incidence of dizziness did not differ significantly between the groups (P>0.05). CONCLUSIONS: These results suggest that the intraoperative administration of ketamine may decrease post-surgical hyperalgesia developing at a region remote from the surgical site. PMID- 28984097 TI - Intra- versus postoperative initiation of pain control via a thoracic epidural catheter for lumbar spinal fusion surgery. AB - BACKGROUND: Thoracic epidural anesthesia (TEA) is one of the pillars of perioperative pain care. Particularly for spine surgery which causes significant postoperative pain TEA seems like an appealing option. However, beneficial effects of a TEA are questionable when the catheter is not used intraoperatively, a decision that is usually based on the surgeon's wish to perform immediate neurological examination postoperatively. METHODS: Forty patients undergoing transforaminal lumbar interbody fusion surgery (TLIF) were randomized into two groups. Patients received preoperative insertion of a TEA. For patients in the intraoperative group an epidural infusion was started preoperatively and maintained throughout. For patients in the postoperative group the epidural infusion was started once neurological examination had been performed. The primary outcome measure in this study was postoperative requirements of piritramide during the first two postoperative hours. Secondary outcomes involved postoperative pain numeric rating scale (NRS) scores, intraoperative opioid requirements, side effects and ability to perform direct postoperative neurological examination. RESULTS: Postoperative group patients required significantly more opioids both intra- and postoperatively (P=0.036 and P=0.039) and NRS scores were significantly higher on admission to recovery, at 30 and 60 min as compared to patients in the intraoperative group (P=0.013; P=0.004 and P=0.012). Early postoperative neurological examination was feasible in all patients in both groups. CONCLUSIONS: Epidural catheters used intraoperatively during TLIF are feasible, significantly reduce pain, intra- and postoperative use of opioids and do not influence the quality of neurological tests directly after the surgical procedure. PMID- 28984098 TI - Role of flexible fiberoptic laryngoscopy in predicting difficult intubation. AB - BACKGROUND: The ability to precisely predict which intubations will be difficult during administration of anesthesia is an important part of preoperative preparation. This study's goal is to accurately identify patients who will be difficult to intubate using the number of tracheal rings observed preoperatively by fiberoptic laryngoscopy. METHODS: We enrolled 994 adult patients in our study who required general anesthesia and orotracheal intubation for their elective surgeries. All patients received a Mallampati Test, a Wilson Risk-Sum Score, and fiberoptic laryngoscopy before operation. Each patient's age, Body Mass Index (BMI), and neck circumference was recorded preoperatively. Logistic regression analysis was applied to evaluate the association between the recorded risk factors and a potentially difficult intubation. The three preoperative assessments were compared using three parameters: positive predictive value, sensitivity, and specificity. RESULTS: The risk factors which were determined to be predictive for difficult intubation were: BMI, neck circumference, Mallampati Test, Wilson Risk-Sum Score, and fiberoptic laryngoscopy (P<0.05). Fiberoptic laryngoscopy as a predictive factor in the preoperative setting had a higher sensitivity, specificity, and positive predictive value than did the Mallampati Test or the Wilson Risk-Sum Score (P<0.05). CONCLUSIONS: Fiberoptic laryngoscopy is a more accurate and convenient preoperative method to predict difficult intubation. PMID- 28984099 TI - Postoperative delirium and postoperative cognitive dysfunction: updates in pathophysiology, potential translational approaches to clinical practice and further research perspectives. AB - Postoperative delirium, the onset of confusion/delirium during the early postoperative phase, is the most common postoperative complication in older adults and represents a medical emergency that requires immediate assessment and treatment. On the other hand, the term postoperative cognitive decline or dysfunction refers to a wide spectrum of clinical conditions featuring a decline in a variety of neuropsychological domains including memory, executive functioning, and speed of processing emerging week to months after anesthesia and surgery. Postoperative delirium and postoperative cognitive decline represent two distinct clinical entities along the continuum of cognitive impairment after anesthesia and surgery. All patients experiencing delirium does however not develop postoperative dysfunction and likewise all patients showing various degree of postoperative decline have not explicitly exhibited postoperative delirium. Although neuroinflammation seems to be main cause, the exact pathophysiology of both phenomena is very difficult to ascertain because it involves the crossroads of many mechanisms. This paper aimed to provide an update in the pathophysiology of these conditions with special attention to the roles of the neuroinflammation, the microglia activation, the surgical stress response, the impairment of neurotransmitter systems, and the direct neurotoxic effect of general anesthetic drugs. Potential translational approaches to clinical practice and further research perspectives are also given. PMID- 28984100 TI - Perioperative ultrasound applied to diagnosis and decision making in anesthesia. AB - INTRODUCTION: Ultrasound is a portable and safe technology that is increasingly used to assist anesthetic procedures and has been integrated into the routine practice of a wide range of invasive procedures. As a complementary diagnostic tool, publications related to perioperative support other than vascular access and nerve blocks are currently lacking. EVIDENCE ACQUISITION: Given the growing interest of anesthesiologists in acquisition of knowledge and skills of ultrasound, we propose a systematic review of the diagnosis, decision making or change in perioperative management of non-cardiac surgical patients derived from ultrasound practice. Of 1112 references found in electronic databases, 62 studies resulted from the screening process. EVIDENCE SYNTHESIS: A complete critical reading of 19 full-text publications was carried out with quantitative analysis of 1825 ultrasound examinations including echocardiography, neck and laryngeal ultrasound, pulmonary ultrasound and abdominal ultrasound, all of them performed by anesthesiologists. Diagnosis applied ultrasound and decision making during perioperative period resulted in change in the management of 31% with 95% CI of 21.06 to 42.04 and odds ratio of 2.68 (1.77 to 4.06) related to hemodynamic, airway and respiratory perioperative management. CONCLUSIONS: Since most of the articles included in this review are observational studies with inherent design concerns, there is an urgent requirement for randomized controlled trials in this area. As anesthesiologists become more comfortable and knowledgeable in ultrasound applied to the perioperative support, emergence of protocols with multidisciplinary ultrasound exploration is expected to allow an improvement in perioperative safety. PMID- 28984101 TI - Possible explanations for the odd phenomenon of liver-assist albumen-dialysis hepatic encephalopathy stepwise "Plateau" electroencephalography recovery. PMID- 28984102 TI - Air pollution during inhalational sedation: it is not all about scavenging! PMID- 28984103 TI - Outcome of geriatric patients admitted to Intensive Care Unit after surgery: the burden of chronic diseases. PMID- 28984104 TI - A simple and cheap simulator for training in spinal anesthesia. PMID- 28984105 TI - Are you "too old" to survive a traumatic brain injury? PMID- 28984106 TI - Climate change in liver preservation? PMID- 28984107 TI - Video-assisted intubating laryngeal mask airway needs evaluation in unstable cervical spine patients. PMID- 28984108 TI - Colonization, contamination, or infection in perineural catheters: how to discriminate? PMID- 28984110 TI - Neuronal cytoplasmic inclusions in tau, TDP-43, and FUS molecular subtypes of frontotemporal lobar degeneration share similar spatial patterns. AB - The 'prion-like' transfer of pathogenic proteins may play a role in the pathogenesis of frontotemporal lobar degeneration (FTLD). Propagation of such proteins along anatomical pathways may give rise to specific spatial patterns of the 'signature' neuronal cytoplasmic inclusions (NCI) characteristic of these disorders. Hence, the spatial patterns of the NCI were compared in three molecular subtypes of FTLD: (1) two variants of FTLD-tau, viz. cortico-basal degeneration (CBD) and Pick's disease (PiD), (2) FTLD with transactive response (TAR) DNA-binding protein 43(TDP-43)-immunoreactive inclusions (FTLD-TDP), and (3) FTLD with 'fused in sarcoma' (FUS)-immunoreactive inclusions (FTLD-FUS). Regardless of molecular pathology, the NCI in the frontal and temporal cortex were most frequently aggregated into clusters, the clusters being regularly distributed parallel to the pia mater. In a significant proportion of regions, the regularly distributed clusters were in the size range 400-800 MUm, approximating the dimension of cell columns associated with the cortico-cortical pathways. Clusters of NCI were significantly larger in FTLD-tau compared with FTLD-TDP and FTLD-FUS. The data suggest that cortical NCI in different molecular subtypes of FTLD all share a similar spatial pattern in the frontal and temporal cortex consistent with a 'prion-like' spread of pathological proteins along anatomical pathways. However, a more selective group of neurons appears to be affected in FTLD-TDP and FTLD-FUS than in FTLD-tau. PMID- 28984111 TI - Dysfunctional lamins as mediators of oxidative stress in Emery-Dreifuss muscular dystrophy. AB - Deficit of lamin A/C or emerin causes genetically transmitted Emery-Dreifuss muscular dystrophy (EDMD). As lamins are considered to be mediators of oxidative stress, the antioxidant/oxidant status was examined. The total oxidant/antioxidant status in serum was examined in 29 cases of Emery-Dreifuss muscular dystrophy. The study included 12 autosomal-dominant laminopathies (AD EDMD), 17 X-linked emerinopathies (X-EDMD) and 20 age-matched normal subjects. Total oxidant status (TOS) was reduced in all cases, and the total antioxidant capacity (TAC) was found to be decreased in the majority of the patients (in 82.8%). A relationship between TOS level and disease progression was noted. No correlation between TOS/TAC level and cardiological or neurological parameters was detected. The results of the study indicate disturbances of redox balance in EDMD patients. Determination of TOS/TAC might help to assess the progress of the disease and the potential effectiveness of antioxidant therapy. PMID- 28984112 TI - Effects of green tea epigallocatechin-3-gallate on the proteolipid protein and oligodendrocyte transcription factor 1 messenger RNA gene expression in a mouse model of multiple sclerosis. AB - The cuprizone multiple sclerosis (MS) animal model is characteristic for toxic demyelination and represents a reversible demyelination and remyelination system. It has been shown that green tea epigallocatechin-3-gallate (EGCG) might be effective in improving the symptoms and pathological conditions associated with autoimmune inflammatory diseases in several animal models. In this study the effects of EGCG on proteolipid protein (PLP) and oligodendrocyte transcription factor 1 (Olig1) expression in the cerebral cortex of a murine model of cuprizone induced demyelination was investigated. C57BL/6 mice were treated with cuprizone for six weeks in order to induce demyelination. Immediately after the cessation of cuprizone the animals were divided into 6 groups (n = 10 for each group). The first two groups were injected intraperitoneally (IP) with EGCG in the amount of 50 mg/kg/daily body weight for 2 and 4 weeks. The second two groups (SHAM) were injected IP with phosphate-buffered saline (PBS) for 2 and 4 weeks, and the third two groups were left without injection as controls. After two and four weeks the mice were killed and the cerebral cortex was collected and the expression of Plp and Olig1 was studied by real-time PCR. The results showed significant increases in PLP and Olig1 expression in the EGCG-treated groups as compared to the SHAM and control groups (p < 0.0001). It is concluded that EGCG increases PLP and Olig1 expression in the cerebral cortex of a mouse model of MS induced by cuprizone. PMID- 28984113 TI - Neuroprotective effect of safranal, an active ingredient of Crocus sativus , in a rat model of transient cerebral ischemia. AB - Safranal is a monoterpene aldehyde found in saffron (Crocus sativus L.) petals. It has been previously reported that safranal has a wide range of activities such as antioxidant and anti-inflammatory effects. In this study, we examined the effect of safranal on brain injuries in a transient model of focal cerebral ischemia. Transient focal cerebral ischemia was induced by middle cerebral artery occlusion for 30 min, followed by 24 h of reperfusion. Safranal in the doses of 72.5 and 145 mg/kg was administered intraperitoneally at 0, 3, and 6 h after reperfusion. Neurobehavioral deficit, infarct volume, hippocampal cell loss and markers of oxidative stress including thiobarbituric acid reactive substances (TBARS), total sulfhydryl (SH) content, and antioxidant capacity (using FRAP assay) were also assessed. The focal cerebral ischemia induced a significant increase in the neurological score, infarct volume and neuronal cell loss in the ipsilateral hippocampal CA1 and CA3 subfields (p < 0.001) and also oxidative stress markers (p < 0.01). Following safranal administration, the total SH content and antioxidant capacity significantly increased, while marked decreases were observed in the neurological score, infarct volume and hippocampal cell loss, as well as TBARS level. This study concluded that safranal had protective effects on ischemic reperfusion injury in the rat model of stroke. Such effects of safranal may have been exerted mainly by suppressing the production of free radicals and increasing antioxidant activity. PMID- 28984115 TI - EBV-positive post-transplant lymphoproliferative disorder presenting as primary diffuse large B-cell lymphoma of the central nervous system. AB - Primary central nervous system post-transplant lymphoproliferative disorder (PCNS PTLD) is a rare complication with inferior survival outcomes in solid organ transplant patients. It represents approximately 7-15% of all PTLD patients. Because of the rarity of this disease, the diagnosis of PCNS-PTLD is often challenging, and the optimal therapy has not been established. We report a case of a renal transplant patient who initially presented with acute altered neurological function, an enhancing mass lesion of the brain on magnetic resonance imaging (MRI), and nonspecific reactive histopathological changes on brain biopsy. The lesion was self-limited and spontaneously resolved without medical treatment for PTLD. Six months later, surveillance MRI revealed recurrence of the brain lesion. The biopsy showed morphologic changes consistent with Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma. The patient responded well to reduction of immunosuppression and treatment with a single agent regimen of rituximab. This is an unusual case of PCNS-PTLD with an initial presentation resembling a self-limited reactive lesion. PMID- 28984114 TI - A novel de novo COL6A1 mutation emphasizes the role of intron 14 donor splice site defects as a cause of moderate-progressive form of ColVI myopathy - a case report and review of the genotype-phenotype correlation. AB - Collagen VI-related myopathy is a group of disorders affecting skeletal muscles and connective tissue. The most common symptoms are muscle weakness and joint deformities which limit the movement and progress over time. Several forms of collagen VI-related myopathies have been described: Bethlem myopathy, an intermediate form and Ullrich congenital muscular dystrophy, which is the most severe. Here we report a novel de novo c.1056+3A>C substitution in intron 14 of the COL6A1 gene encoding alpha-chains of collagen VI in a 13-year-old girl suffering from collagen VI (ColVI) myopathy. Analysis performed on cDNA generated from the RNA obtained from the patient's blood cells showed that the reported variant leads to the entire exon 14 skipping and probably results in an in-frame deletion of 18 amino acids of the COL6A1 protein. Clinical presentation, abnormal secretion of the collagen demonstrated in muscle biopsy and the COL6A1 c.1056+3A>C mutation justify classification of the presented case as ColVI myopathy with moderate-progressive course. Analysis of the literature indicates that the donor splice site of COL6A1 intron 14, associated with the phenotype of Bethlem myopathy or intermediate form, is a hot spot for ColVI myopathies. PMID- 28984116 TI - Cerebellar liponeurocytoma with atypical histological features - a rare example of a glioneuronal tumor. AB - We present a case of a rare neoplasm in a 77-year-old woman with previous oncological history, who developed a rapid onset of cerebellar symptoms. The neuroimaging detected a posterior fossa tumor suspected of meningioma which was completely resected soon after. Histologically the neoplasm had two components with different immunophenotype. One constituent was lobular, composed of monotonous mitotically active round cells with a predominant neuronal profile. The second, astrocytic component contained lipomatous cells intermixed with larger gemistocytic astrocytes. Fields of geographic necrosis as well as multifocal microvascular proliferation were observed. The Ki67 proliferation index was 12%. After two years of follow-up the patient remains free of symptoms and radiologic recurrence. The presented case of cerebellar liponeurocytoma is unusual in terms of its atypical histological features and prominent astrocytic component. The authors propose that the term 'lipomatous glioneuronal tumor' seems to be more appropriate for this type of lesion, considering its histologic spectrum and possible extracerebellar location. PMID- 28984117 TI - Sudden unexpected postnatal collapse at 20 hours from birth during skin-to-skin care related to brainstem developmental alterations - a case report. AB - This report describes a case of sudden collapse of a 20-hour-old newborn, while he was placed close to their mother according to skin-to-skin care, attributed to developmental alterations of brainstem nuclei involved in regulation of the vital functions. The infant, after a normal pregnancy, appeared well developed at birth, with no evidence of malformations or trauma, but showing severe asphyxia. The routine autopsy did not reveal a possible cause of death. Only the in-depth anatomopathological examination of the autonomic nervous system, according to the protocol developed by the "Lino Rossi" Research Center of Milan University, provided an explanation of the pathogenetic mechanism of this early death. The sudden death, a few hours after birth, was the unavoidable outcome of a complex of abnormalities of brainstem nuclei, particularly of the Kolliker-Fuse nucleus, an essential structure for eupneic breathing at birth, exacerbated by the prone position implied by the skin-to-skin contact. PMID- 28984118 TI - Intracerebral hemorrhage in the context of cerebral amyloid angiopathy and varied time of onset of cerebral venous thrombosis: a case report. AB - In patients with cerebral venous thrombosis (CVT) the incidence of intracerebral hemorrhage (ICH) is estimated at about 37% and subarachnoid hemorrhage (SAH) at 1% of patients. A case with coincident occurrence of ICH, SAH and CVT in a patient with cerebral amyloid angiopathy (CAA) is reported. A 79-year-old woman was admitted to the Neurological Department after the occurrence of generalized seizures, the first in her life. On admission she was unconscious with right hemiparesis and deviation of eyes to the left. On computed tomography (CT) scan many hemorrhagic infarcts were present in the frontal, parietal, temporal and left occipital lobes. Angio-CT revealed thrombosis in the right transverse sinus, right internal carotid vein and superior sagittal sinus. Her state slowly deteriorated. She died after 6 days. Neuropathologically, many hemorrhagic infarcts were observed in cortical regions in the vicinity of veins with thrombosis and in the white matter. The varied time of onset of thrombosis of the right sigmoid sinus, right superior petrosal sinus, superior sagittal sinus, right transverse sinus and the proximal part of the right internal carotid vein was confirmed. cerebral amyloid angiopathy in brain vessels was diagnosed. Subarachnoid hemorrhage is a very uncommon presentation of CVT and may coexist with CAA. We can only speculate that CAA may have an effect on vein destruction and can promote cerebral vein thrombosis and in consequence also predispose to intracerebral hemorrhage and subarachnoid hemorrhage. The most probable cause of extensive thrombosis was a coagulation disorder. PMID- 28984119 TI - Neurochemical Conference 2017: "Advances in molecular and epigenetic mechanisms in neurodegeneration and neuroinflammation: novel therapeutic approaches". PMID- 28984120 TI - Summary of global update on preventive chemotherapy implementation in 2016: crossing the billion. PMID- 28984121 TI - Global programme to eliminate lymphatic filariasis: progress report, 2016. PMID- 28984122 TI - Effect of Current on Diffusivity in Metal Hexaborides: A Spark Plasma Sintering Study. AB - We present the effect of pulsed direct current on metal ion diffusion in CaB6 SrB6 diffusion couples, showing that the diffusivity of Ca2+ and Sr2+ across the diffusion couple interface is higher toward the positive electrode when subjected to a current flow of 2.2 kA at a temperature of 2007 K. We attribute this enhanced mobility to the movement of negatively charged metal vacancies toward the positive electrode in the system. Energy-dispersive spectroscopy is used to map the concentration of Ca2+ and Sr2+ in the region near the interface, and diffusion profiles are fitted with error functions. The concentration curves display concentration-dependent Boltzmann-Matano diffusivity. Total dopant values (Q) have been used to numerically compare the differences between Ca2+ diffusion in SrB6 and Sr2+ diffusion in CaB6. We determine an enhancement of 3.8* for Ca2+ into SrB6 versus an enhancement of 1.8* for Sr2+ into CaB6. No new phases are formed at the interface between CaB6 and SrB6, since hexaboride compounds readily form solid solutions. The results elucidate the role of pulsed direct current on the diffusion of metal ions in hexaboride compounds. PMID- 28984123 TI - Oxidation Mechanism of Si1-xGex Nanowires with Au Catalyst Tip as a Function of Ge Content. AB - Si1-xGex nanowires (NWs) (0.22 <= x <= 0.78) were synthesized using a vapor liquid-solid procedure with a Au catalyst. We measured the intrinsic physical, chemical, and electrical properties of the oxidized Si1-xGex NWs using several techniques, including transmission electron microscopy, X-ray photoemission spectroscopy, and optical pump-THz probe spectroscopy. We suggest two distinct oxidation mechanisms depending on the Ge content in the Si1-xGex NWs: (i) when the Ge content is around 0.22, a Au catalytic effect brings about oxidation in both the axial and lateral directions; and (ii) when the Ge content is greater than 0.22, the Au tip is detached from the NW body and does not act as a catalyst, which is a result of the high degree of Ge-atom participation in the oxidation process. Additionally, we measured the photoconductivity decay time distribution for the Si1-xGex NWs before and after oxidation process; the decay time is significantly shortened in oxidized Si1-xGex NWs (0.22 < x), whereas it is maintained for Si-rich Si1-xGex NWs (x ~ 0.22) as compared to the as-grown Si1 xGex NWs. It indicates that the number of defect states is generated with the formation of defective Ge oxide at the oxide-shell-layer/Si1-xGex-core-NW interface. PMID- 28984124 TI - Interfacial Separation-Enabled All-Dry Approach for Simultaneous Visualization, Transfer, and Enhanced Raman Analysis of Latent Fingerprints. AB - It is of essential importance to visualize latent fingerprint (LFP) and analyze the compounds therein. For this purpose, various approaches have been developed but suffer from low imaging and/or detection efficiency. Most importantly, most of them require a necessary in-solution process and thus are not applicable to LFPs on bulky or water-sensitive substrates. In this work, we report an all-dry method to achieve simultaneous visualization and transfer of LFP and enhanced Raman analysis of multiple species therein. In this innovative approach, polydopamine (PDA) film-coated poly(dimethylsiloxane) (PDMS) flake with dense plasmonic silver nanoparticles (AgNPs@PDA@PDMS) was applied to cover the substrate carrying LFP. After gentle separation, the AgNPs@PDA film was transferred from PDMS to the LFP ridges to visualize a positive LFP pattern on the substrate, leaving behind a complementary (negative) LFP pattern on the PDMS flake. The compounds in the LFP were further analyzed via the AgNP-enhanced Raman technique. This approach enables high-contrast and full-feature visualization and transfer of LFP on arbitrary nonporous substrates and facilitates sensitive Raman analysis of multiple species in the sweat and thus promises great potential for practical applications. PMID- 28984125 TI - Self-Healing of Polymer in Acidic Water toward Strength Restoration through the Synergistic Effect of Hydrophilic and Hydrophobic Interactions. AB - To improve reliability, durability, and reworkability of bulk polymers utilized in ubiquitous acidic water, the authors develop a novel hyperbranched polymer capable of self-healing and recycling in a low-pH aqueous environment. The hyperbranched polymer has many hydrophilic and hydrophobic terminal groups. When it is damaged in acidic water, the hydrophilic groups are protonated, forming hydrogen bonds, and closing the crack. Meanwhile, hydrophobic interactions of hydrophobic groups are gradually established across the interface because of the intimate contact of the cracked surface, further reinforcing the rebonded portion. The amphiphilic structure proves to meet both the thermodynamic and kinetic requirements for autonomous rehabilitation. As a result, the unfavored water, which used to impede adhesion between hydrophobic polymeric materials, turns into a positive aid to crack healing. The mechanism involved is carefully analyzed and verified in terms of micro- and macroscopic techniques. The proposed operating environment-oriented design of the stimulus-responsive macromolecule may help to broaden the family of underwater self-healing polymers and their application scope. PMID- 28984126 TI - Light-Induced Cell Alignment and Harvest for Anisotropic Cell Sheet Technology. AB - Well-organized orientation of cells and anisotropic extracellular matrix (ECM) are crucial in engineering biomimetic tissues, such as muscles, arteries, and nervous system, and so on. This strategy, however, is only beginning to be explored. Here, we demonstrated a light-induced cell alignment and harvest for anisotropic cell sheets (ACS) technology using light-responsive TiO2 nanodots film (TNF) and photo-cross-linkable gelatin methacrylate (GelMA). Cell initial behaviors on TNF might be controlled by micropatterns of light-induced distinct surface hydroxyl features, owing to a sensing mechanism of myosin II-driven retraction of lamellipodia. Further light treatment allowed ACS detachment from TNF surface while simultaneously solidified the GelMA, realizing the automatic transference of ACS. Moreover, two detached ACS were successfully stacked into a 3D bilayer construct with controllable orientation of individual layer and maintained cell alignment for more than 7 days. Interestingly, the anisotropic HFF-1 cell sheets could further induce the HUVECs to form anisotropic capillary like networks via upregulating VEGFA and ANGPT1 and producing anisotropic ECM. This developed integrated-functional ACS technology therefore provides a novel route to produce complex tissue constructs with well-defined orientations and may have a profound impact on regenerative medicine. PMID- 28984128 TI - Unraveling the Dynamics of Nanoscopically Confined PVME in Thin Films of a Miscible PVME/PS Blend. AB - Broadband dielectric spectroscopy (BDS) was employed to investigate the glassy dynamics of thin films (7-200 nm) of a poly(vinyl methyl ether) (PVME)/polystyrene (PS) blend (50:50 wt %). For BDS measurements, nanostructured capacitors (NSCs) were employed, where films are allowed a free surface. This method was applied for film thicknesses up to 36 nm. For thicker films, samples were prepared between crossed electrode capacitors (CECs). The relaxation spectra of the films showed multiple processes. The first process was assigned to the alpha-relaxation of a bulklike layer. For films measured by NSCs, the rates of alpha-relaxation were higher compared to those of the bulk blend. This behavior was related to the PVME-rich free surface layer at the polymer/air interface. The second process was observed for all films measured by CECs (process X) and the 36 nm film measured by NSCs (process X2). This process was assigned to fluctuations of constraint PVME segments by PS. Its activation energy was found to be thickness-dependent because of the evidenced thickness dependency of the compositional heterogeneity. Finally, a third process with an activated temperature dependence was observed for all films measured by NSCs (process X1). It resembled the molecular fluctuations in an adsorbed layer found for thin films of pure PVME, and thus, it is assigned accordingly. This process undergoes an extra confinement because of frozen adsorbed PS segments at the polymer/substrate interface. To our knowledge, this is the first example where confinement-induced changes were observed by BDS for blend thin films. PMID- 28984127 TI - Critical Intermediate Structure That Directs the Crystalline Texture and Surface Morphology of Organo-Lead Trihalide Perovskite. AB - We have identified an often observed yet unresolved intermediate structure in a popular processing with dimethylformamide solutions of lead chloride and methylammonium iodide for perovskite solar cells. With subsecond time-resolved grazing-incidence X-ray scattering and X-ray photoemission spectroscopy, supplemental with ab initio calculation, the resolved intermediate structure (CH3NH3)2PbI2Cl2.CH3NH3I features two-dimensional (2D) perovskite bilayers of zigzagged lead-halide octahedra and sandwiched CH3NH3I layers. Such intermediate structure reveals a hidden correlation between the intermediate phase and the composition of the processing solution. Most importantly, the 2D perovskite lattice of the intermediate phase is largely crystallographically aligned with the [110] planes of the three-dimensional perovskite cubic phase; consequently, with sublimation of Cl ions from the organo-lead octahedral terminal corners in prolonged annealing, the zigzagged octahedral layers of the intermediate phase can merge with the intercalated methylammonium iodide layers for templated growth of perovskite crystals. Regulated by annealing temperature and the activation energies of the intermediate and perovskite, deduced from analysis of temperature dependent structural kinetics, the intermediate phase is found to selectively mature first and then melt along the layering direction for epitaxial conversion into perovskite crystals. The unveiled epitaxial conversion under growth kinetics controls might be general for solution-processed and intermediate-templated perovskite formation. PMID- 28984129 TI - Interfacial Chemistry Regulation via a Skin-Grafting Strategy Enables High Performance Lithium-Metal Batteries. AB - The lithium (Li) metal anode suffers severe interfacial instability from its high reactivity toward liquid electrolytes, especially carbonate-based electrolytes, resulting in poor electrochemical performance of batteries that use 4 V high capacity cathodes. We report a new skin-grafting strategy that stabilizes the Li metal-liquid electrolyte interface by coating the Li metal surface with poly((N 2,2-dimethyl-1,3-dioxolane-4-methyl)-5-norbornene-exo-2,3-dicarboximide), a chemically and electrochemically active polymer layer. This layer, composed of cyclic ether groups with a stiff polycyclic main chain, serves as a grafted polymer skin on the Li metal anode not only to incorporate ether-based polymeric components into the solid-electrolyte interphase (SEI) but also to accommodate Li deposition/dissolution under the skin in a dendrite/moss-free manner. Consequently, a Li-metal battery employing a Li metal anode with the grafted skin paired with LiNi0.5Co0.2Mn0.3O2 cathode has a 90.0% capacity retention after 400 charge/discharge cycles and a capacity of 1.2 mAh/cm2 in a carbonate-based electrolyte. This proof-of-concept study provides a new direction for regulating the interfacial chemistry of Li metal anodes and for enabling high-performance Li metal batteries. PMID- 28984130 TI - Ammonia Emissions May Be Substantially Underestimated in China. AB - China is a global hotspot of atmospheric ammonia (NH3) emissions and, as a consequence, very high nitrogen (N) deposition levels are documented. However, previous estimates of total NH3 emissions in China were much lower than inference from observed deposition values would suggest, highlighting the need for further investigation. Here, we reevaluated NH3 emissions based on a mass balance approach, validated by N deposition monitoring and satellite observations, for China for the period of 2000 to 2015. Total NH3 emissions in China increased from 12.1 +/- 0.8 Tg N yr-1 in 2000 to 15.6 +/- 0.9 Tg N yr-1 in 2015 at an annual rate of 1.9%, which is approximately 40% higher than existing studies suggested. This difference is mainly due to more emission sources now having been included and NH3 emission rates from mineral fertilizer application and livestock having been underestimated previously. Our estimated NH3 emission levels are consistent with the measured deposition of NHx (including NH4+ and NH3) on land (11-14 Tg N yr-1) and the substantial increases in NH3 concentrations observed by satellite measurements over China. These findings substantially improve our understanding on NH3 emissions, implying that future air pollution control strategies have to consider the potentials of reducing NH3 emission in China. PMID- 28984131 TI - In Situ Detection of the Adsorbed Fe(II) Intermediate and the Mechanism of Magnetite Electrodeposition by Scanning Electrochemical Microscopy. AB - Electrodeposition is an important approach that can produce functional compound materials by assembling multiple species at the electrode surface. However, a fundamental understanding of the electrodeposition mechanism has been limited by its complexity and is often gained only through ex situ studies of deposited materials. Here we report on the application of scanning electrochemical microscopy (SECM) to enable the in situ, real-time, and quantitative study of electrodeposition and electrodissolution. Specifically, we electrodeposit magnetite (Fe3O4) from an alkaline solution of Fe(III)-triethanolamine as a robust route that can prepare this magnetic and electrocatalytic compound on various conductive substrates. The powerful combination of SECM with cyclic voltammetry (CV) at a gold substrate reveals that the electrodeposition of magnetite requires the preceding adsorption of Fe(II)-triethanolamine on the substrate surface and, subsequently, is mediated through the highly complicated ECadsCmag mechanism, where both chemical steps occur at the substrate surface rather than in the homogeneous solution. SECM-based CV is obtained under high mass-transport conditions and analyzed by the finite element method to kinetically resolve all steps of the ECadsCmag mechanism and quantitatively determine relevant reaction parameters. By contrast, the adsorbed Fe(II) intermediate is unresolvable from co-deposited magnetite in situ by other electrochemical techniques and is undetectable ex situ because of the facile air oxidation of the Fe(II) intermediate. Significantly, SECM-based CV will be useful for the in situ characterization of various electrodeposited compounds to complement their ex situ characterization. PMID- 28984132 TI - Evaluating Single-Cell DNA Damage Induced by Enhanced Radiation on a Gold Nanofilm Patch. AB - Although radiotherapy is a general oncology treatment and is often synergistically applied with surgery and chemotherapy, it can cause side effects during and after treatment. Gold nanoparticles were studied as a potential material to enhance radiation to induce damage in cancer cells. However, few studies have been conducted to examine the effects of gold nanofilm on cell impairment under X-ray treatment. This paper describes a microfabrication-based single-cell array platform to evaluate DNA damage induced by enhanced X-ray radiation on gold nanofilm patches (GNFPs). Cancer cells were patterned on GNFPs of different diameters and thicknesses, where each cell was attached on one GNFP. The end-point DNA damage induced by X-ray was examined in situ at the single-cell level using a halo assay. The preliminary data demonstrated that the enhancement of DNA damage was significantly related to the area and thickness of the GNFP. This platform may be hopefully used to establish the mathematical relationships among DNA damage, X-ray dosage, and thickness and area of the GNFP, and further contribute to radiation dosage screening for personalized radiotherapy. PMID- 28984133 TI - Evaporative Optical Marangoni Assembly: Tailoring the Three-Dimensional Morphology of Individual Deposits of Nanoparticles from Sessile Drops. AB - We have recently devised the evaporative optical Marangoni assembly (eOMA), a novel and versatile interfacial flow-based method for directing the deposition of colloidal nanoparticles (NPs) on solid substrates from evaporating sessile drops along desired patterns using shaped UV light. Here, we focus on a fixed UV spot irradiation resulting in a cylinder-like deposit of assembled particles and show how the geometrical features of the single deposit can be tailored in three dimensions by simply adjusting the optical conditions or the sample composition, in a quantitative and reproducible manner. Sessile drops containing cationic NPs and a photosensitive surfactant at various concentrations are allowed to evaporate under a single UV beam with a diameter much smaller than that of the drop. After complete evaporation, the geometrical characteristics of the NP deposits are precisely assessed using optical profilometry. We show that both the volume and the radial size of the light-directed NP deposit can be adjusted by varying the diameter or the intensity of the UV beam or alternatively by changing the concentration of the photosensitive surfactant. Notably, in all these cases, the deposits display an almost constant median height corresponding to a few layers of particles. Moreover, both the radial and the axial extent of the patterns are tuned by changing the NP concentration. These results are explained by the correlation among the strength of Marangoni flow, the particle trapping efficiency, and the volume of the deposit, and by the role of evaporation-driven flow in strongly controlling the deposit height. Finally, we extend the versatility of eOMA by demonstrating that NPs down to 30 nm in diameter can be effectively patterned on glass or polymeric substrates. PMID- 28984135 TI - Smart Combination of Cyclodextrin Polymer Host-Guest Recognition and Mg2+ Assistant Cyclic Cleavage Reaction for Sensitive Electrochemical Assay of Nucleic Acids. AB - A novel enzyme-free electrochemical sensing strategy was proposed for sensitive monitoring of DNA and miRNA by smart combination of the cyclic cleavage reaction of Mg2+-dependent DNAzyme and the host-guest inclusion between ferrocene-labeled hairpin probe (H-1) and nitrogen-doped reduced graphene oxide/beta-cyclodextrin polymer (NRGO/beta-CDP) nanocomposites. The synthesized NRGO/beta-CDP nanocomposites with high electrocatalytic activity and recognition capability were modified on the glassy carbon electrode to construct the sensing platform. Upon the hybridization reaction of subunit DNA in the loop region with target sequence, the active DNAzyme was liberated from the caged structure, which bound with H-1 to catalyze its cleavage in the presence of Mg2+ and triggered the target recycling amplification for the cleavage of a large number of H-1. Each cleaved H-1 was divided into two single-stranded oligonucleotides, leading to an obvious enhancement of peak current by the molecular recognition of beta-CDP on the electrode. Thus, the constructed biosensor showed high sensitivity and selectivity for DNA and miRNA assays, with wide concentration ranges of 0.01-1000 and 0.05-500 pM and low detection limits of 3.2 and 18 fM, respectively. This developed sensing strategy may become a promising nucleic acid detection method in bioassays and clinical diagnosis. PMID- 28984134 TI - Ultrafast CO Kinetics in Heme Proteins: Adiabatic Ligand Binding and Heavy Atom Tunneling. AB - The ultrafast kinetics of CO rebinding to carbon monoxide oxidation activator protein (ChCooA) are measured over a wide temperature range and compared with the kinetics of CO binding in other heme systems such as myoglobin (Mb) and hemoglobin (Hb). The Arrhenius prefactor for CO binding to ChCooA and protoheme (~1011 s-1) is similar to what is found for spin-allowed NO binding to heme proteins and is several orders of magnitude larger than the prefactor of Mb and Hb (~109 s-1). This indicates that the CO binding reaction is adiabatic, in contrast to the commonly held view that it is nonadiabatic due to spin-forbidden (DeltaS = 2) selection rules. Under the adiabatic condition, entropic factors, rather than spin-selection rules, are the source of the reduced Arrhenius prefactors associated with CO binding in Mb and Hb. The kinetic response of ChCooA-CO is nonexponential at all temperatures, including 298 K, and is described quantitatively using a distribution of enthalpic rebinding barriers associated with heterogeneity in the heme doming conformation. Above the solvent glass transition (Tg ~ 180 K), the rebinding progress slows as temperature increases, and this is ascribed to an evolution of the distribution toward increased heme doming and larger enthalpic barriers. Between Tg and ~60 K, the nonexponential rebinding slows down as the temperature is lowered and the survival fraction follows the predictions expected for a quenched barrier distribution. Below ~60 K the rebinding kinetics do not follow these predictions unless quantum mechanical tunneling along the heme doming coordinate is also included as an active channel for CO binding. PMID- 28984136 TI - New Quantitative Structure-Activity Relationship Model for Angiotensin-Converting Enzyme Inhibitory Dipeptides Based on Integrated Descriptors. AB - Angiotensin-converting enzyme (ACE) inhibitory peptides derived from food proteins have been widely reported for hypertension treatment. In this paper, a benchmark data set containing 141 unique ACE inhibitory dipeptides was constructed through database mining, and a quantitative structure-activity relationships (QSAR) study was carried out to predict half-inhibitory concentration (IC50) of ACE activity. Sixteen descriptors were tested and the model generated by G-scale descriptor showed the best predictive performance with the coefficient of determination (R2) and cross-validated R2 (Q2) of 0.6692 and 0.6220, respectively. For most other descriptors, R2 were ranging from 0.52 to 0.68 and Q2 were ranging from 0.48 to 0.61. A complex model combining all 16 descriptors was carried out and variable selection was performed in order to further improve the prediction performance. The quality of model using integrated descriptors (R2 0.7340 +/- 0.0038, Q2 0.7151 +/- 0.0019) was better than that of G-scale. An in-depth study of variable importance showed that the most correlated properties to ACE inhibitory activity were hydrophobicity, steric, and electronic properties and C-terminal amino acids contribute more than N-terminal amino acids. Five novel predicted ACE-inhibitory peptides were synthesized, and their IC50 values were validated through in vitro experiments. The results indicated that the constructed model could give a reliable prediction of ACE-inhibitory activity of peptides, and it may be useful in the design of novel ACE-inhibitory peptides. PMID- 28984137 TI - Imaging and clinical end points in brain metastases trials. PMID- 28984138 TI - Val66Met Polymorphism in BDNF Has No Sexual and APOE epsilon4 Status-Based Dimorphic Effects on Susceptibility to Alzheimer's Disease: Evidence From an Updated Meta-Analysis of Case-Control Studies and High-Throughput Genotyping Cohorts. AB - Some studies showed that Val66Met polymorphism of brain-derived neurotrophic factor (BDNF) conveys susceptibility to Alzheimer's disease (AD) in females only. However, the confounding effects of some risk factors for AD were omitted in these studies. The aim of this meta-analysis comprising 19 604 patients with AD and 26 333 controls was to reexamine the association between Val66Met and AD by conditioning the effects of age, sex, and/or apolipoprotein E ( APOE) epsilon4 status. In agreement with the previous meta-analysis, Val66Met was associated with AD in females without confounding adjustment (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.03-1.14; P = .003). Nevertheless, after adjusting for age and APOE epsilon4 status, Val66Met was not associated with AD in females (OR, 1.02; 95% CI, 0.94-1.11; P = .57). This comprehensive meta-analysis with the largest sample size demonstrated no association could be observed between Val66Met and AD in general or by dividing samples based on sex or APOE epsilon4. PMID- 28984139 TI - Neurological improvement of perineural and leptomeningeal spread of squamous cell carcinoma treated with intrathecal chemotherapy and systemic EGFR inhibition. AB - Squamous cell carcinoma (SCC) is a common cancer of the skin. Risk factors include fair skin, excessive sun and ultraviolet light exposure, and history of xeroderma pigmentosa. Perineural invasion (PNI), an uncommon manifestation of SCC, involves microscopic tumor cells invading various layers of the nerve sheath. It is associated with a poorer prognosis. Standard treatment for PNI includes radiation therapy. Here, we describe a case an older gentleman with a history of SCC with PNI successfully treated with erlotinib and intrathecal chemotherapy. PMID- 28984140 TI - Spinal cord involvement in two children with posterior reversible encephalopathy syndrome. AB - Spinal cord involvement (SCI) is a rare feature of posterior reversible encephalopathy syndrome (PRES), especially in children. SCI is generally symptomatic, and may have a different outcome compared with encephalic localization of PRES. We reported about two cases of SCI in pediatric patients with PRES, after multimodal anticancer therapies, including radiotherapy, chemotherapy and targeted agents. PMID- 28984141 TI - Dabrafenib and trametinib in BRAFV600E mutated glioma. AB - BRAFV600E mutations have been identified in a number of glioma subtypes, most frequently in pleomorphic xanthoastrocytoma, ganglioglioma, pilocytic astrocytoma, and epithelioid glioblastoma. Although the development of BRAF inhibitors has dramatically improved the clinical outcome for patients with BRAFV600E mutant tumors, resistance develops in a majority of patients due to reactivation of the MAPK pathway. Addition of MEK inhibition to BRAF inhibition improves survival. Here we report successful treatment of two patients with BRAFV600E mutant pleomorphic xanthoastrocytoma using the BRAF inhibitor dabrafenib in combination with the MEK inhibitor trametinib. PMID- 28984142 TI - Visual inspection of MR relative cerebral blood volume maps has limited value for distinguishing progression from pseudoprogression in glioblastoma multiforme patients. AB - AIM: We examined whether visual interpretation of relative cerebral blood volume (rCBV) color maps made with dynamic susceptibility-weighted perfusion MRI can reliably distinguish progressive disease (PD) from pseudoprogression (PsPD) in glioblastoma patients during treatment with temozolomide chemoradiation. MATERIALS & METHODS: Magnetic resonance (MR) perfusion-weighted images were evaluated based on visual inspection of rCBV maps. Sensitivity and specificity were calculated to assess if rCBV can reliably differentiate between PD and PsPD, during standard chemoradiation therapy. RESULTS: Evaluation of dynamic susceptibility-weighted contrast-enhanced perfusion MRI by visual interpretation of rCBV maps did not differentiate PD from PsPD (sensitivity = 72%; specificity = 23%). Furthermore, the interpretation of the rCBV maps had no prognostic value regarding survival. CONCLUSION: Qualitative rCBV-based dynamic susceptibility weighted contrast-enhanced perfusion MRI does not reliably differentiate PD from PsPD, and is not prognostic for survival in glioblastoma multiforme patients during treatment with temozolomide chemoradiation. PMID- 28984143 TI - The textbook: An endangered species. PMID- 28984144 TI - The feasibility of brief dog-assisted therapy on university students stress levels: the PAwS study. AB - BACKGROUND: Pet therapy is becoming increasingly popular and is used in a variety of ways from encouraging communication in older adults to improving wellbeing in those with serious mental illness. Increasingly Universities have been offering pet therapy to students in an effort to reduce stress. However, little evidence currently exists to support the effectiveness of reducing measurable stress levels after a standalone drop-in unstructured session. The University of Sheffield's Counselling Service works in partnership with Guide Dogs for the Blind to give students access to calm, well-trained animals for informal group stress relief. AIMS: To assess the feasibility of implementing and evaluating unstructured group interventions with a Guide Dog in training within the university student population. METHODS: One hundred and thirty-one students who attended pet therapy at the University Counselling Service were recruited on a voluntary basis to take part in the research. Stress, measured on the state trait anxiety inventory, and blood pressure were taken before and after a 15-min intervention. RESULTS: All measures showed a statistically significant reduction immediately after the intervention. CONCLUSION: Short interactions with a Guide Dog in training appear to reduce stress in University students. A controlled study is required to investigate further. PMID- 28984145 TI - Central nervous system complications after allogeneic hematopoietic stem cell transplantation. AB - Allogenic hematopoietic stem cell transplant (alloSCT) is a potentially curative modality of treatment for patients with hematological malignancies. However, CNS complications following transplant pose a risk to survival of the patients. Early recognition and management of these complications are crucial to reduce morbidity and mortality of patients following transplant. Early CNS complications associated with alloSCT are infection, cerebrovascular events, chemotherapy and radiation-induced toxicities while late complications include post-transplant lymphoproliferative disorder, CNS relapse of underlying malignancy and viral and fungal infections. Development of graft-versus-host disease can further increase the risk of CNS complications and outcomes after alloSCT. Strategies aimed to reduce the risk of CNS complications and early management may ameliorate the morbidity and mortality in transplant recipients. PMID- 28984146 TI - Nonclinical safety assessment of SPX-101, a novel peptide promoter of epithelial sodium channel internalization for the treatment of cystic fibrosis. AB - BACKGROUND: ENaC inhibition has long been an attractive therapeutic target for the treatment of cystic fibrosis. However, previous attempts at developing ENaC inhibitors have been unsuccessful due to complications arising from systemic circulation of the compounds. Here, we describe the preclinical toxicology assessment of a new inhaled peptide promoter of ENaC internalization delivered as a nebulized aerosol. METHODS: Preclinical assessment of SPX-101 safety was determined using an in vitro hERG assay, bolus injection of SPX-101 in a canine cardiovascular and respiratory safety pharmacology model and 28-day inhalation toxicology studies of nebulized drug in rats and dogs. RESULTS: SPX101 had no effects on the respiratory, cardiac or central nervous systems. The 28-day inhalation toxicology studies of nebulized SPX-101 in rats and dogs revealed no drug-related adverse events. Plasma levels of SPX-101 peaked less than 1 h after the end of treatment in rats and were below the limit of detection in canine models. CONCLUSIONS: SPX-101, a novel peptide promoter of ENaC internalization, elicited no adverse effects at doses up to the MFD and in excess of the highest preclinical efficacious and expected clinical doses. In contrast to channel blockers like amiloride and derivative small molecules, SPX-101 does not achieve significant systemic circulation, thus doses are not limited due to toxic side effects like hyperkalemia and weight loss. PMID- 28984148 TI - Integrated Behavioral Health Care in Pediatric Primary Care: A Quality Improvement Project. AB - The top 5 reasons for pediatric office visits in the United States today are behavioral health concerns. This article describes a colocated behavioral health and care coordination integration model in a pediatric primary care office to reduce barriers to behavioral health care. PMID- 28984147 TI - Celastrol ameliorates acetaminophen-induced oxidative stress and cytotoxicity in HepG2 cells. AB - Acetaminophen (APAP) is the most commonly used analgesic and antipyretic drug in the world. However, hepatotoxicity caused by APAP overdose is the most frequent cause of acute liver failure worldwide and oxidative stress involved in the pathogenesis of APAP hepatotoxicity. Celastrol is a natural triterpenoid derived from Tripterygium wilfordii Hook F. that exhibits antioxidant, anti-inflammatory, and antitumor activities. In this study, we aimed to investigate the potential ameliorative effects of celastrol against APAP-induced cytotoxicity and oxidative stress. Human hepatocellular carcinoma cells (HepG2) were incubated with 20 mM of APAP for 24 h and posttreated with 50 nM, 100 nM, or 200 nM of celastrol for a further 24 h. The methylthiazolyldiphenyl-tetrazolium bromide, lactate dehydrogenase, and neutral red uptake assays showed celastrol posttreatments recovered cell viability and cell membrane integrity in a concentration-dependent manner. Celastrol posttreatments exerted a significant increase in the glutathione content and a decrease in the malondialdehyde and protein carbonylation levels. Also, celastrol posttreatments attenuated the APAP-induced oxidative stress by raising glutathione peroxidase, glutathione reductase, and catalase activities. However, superoxide dismutase activity did not change. In conclusion, celastrol treatment may improve cell viability and increase cellular antioxidant defense in HepG2 cells. These results suggest that celastrol may have the potential to ameliorate the APAP-induced oxidative stress and cytotoxicity. PMID- 28984149 TI - Support and negation of colorectal cancer risk prevention behaviors: analysis of spousal discussions. AB - The shared social context created in a marriage may be important in motivating engagement in health behaviors, but spousal influence may not be uniformly applied. Our goal was to examine how spouses discuss health behaviors relevant for colorectal cancer (CRC) risk-reduction to better understand how spouses exert or fail to exert influence. In this pilot study, first degree relatives of CRC patients and their spouses completed demographic and self-reported health questionnaires. After a genetic counseling session regarding risk and risk reduction, couples engaged in a semi-structured discussion task to discuss lifestyle choices they currently undertake or could undertake to reduce risk. Demographic and health data was analyzed using descriptive statistics. Using a directed content analysis based on the transtheoretical model of behavior change, we coded discussion transcripts for depth and direction of talk for seven behavioral CRC risk factors. Spouses engaged in several strategies to reduce their risk for CRC, and problem-solved together to increase these preventative efforts. All couples mentioned diet and exercise as important factors in CRC risk; however, other risk factors received less attention. Despite evidence of support and encouragement, spouses ignored, minimized, or negated the importance of some health behaviors. Spousal influence could be an important tool to improve participation in health behaviors, but more guidance may be necessary to hold couples accountable to evidence-based guidelines to reduce risk. Health care providers should address couples as a unit to assess and address health behaviors. PMID- 28984150 TI - Health related quality of life impact from rotavirus diarrhea on children and their family caregivers in Thailand. AB - BACKGROUND: Rotavirus diarrhea is a major health problem among young children worldwide with potential negative impacts on health-related quality of life (HRQoL). This study assessed the impact of rotavirus diarrhea on HRQoL of children and their caregivers. METHODS: We performed a cross-sectional study among 460 hospitalized children with diarrhea aged under 5 years and their family caregivers at three hospitals in Phetchabun province, Thailand during May 2013 and February 2014. The severity of diarrhea was assessed using the Vesikari severity scoring system while the HRQoL was assessed using the EQ-5D-3L. RESULTS: The mean EQ-5D utility of children with all-causes diarrhea was 0.604. The utility of the rotavirus diarrhea group was significantly lower than that of the non-rotavirus diarrhea group (0.593 vs. 0.612; p-value = 0.040). The family caregiver's utility was 0.964 at baseline and significantly decreased to 0.620 (p value = 0.041) when their children were hospitalized with diarrhea. In multiple regression analyses, severity but not rotavirus infection had significant negative impacts on the utility of both the children and their caregivers. CONCLUSION: Diarrhea, either caused by rotavirus or non-rotavirus infection, resulted in substantial negative impacts on the quality of life of both the children and their caregivers. PMID- 28984151 TI - Testing the 2 * 2 model of perfectionism in Ecuadorian adolescent population. AB - This study aimed to test the 2 * 2 model of dispositional perfectionism in an Ecuadorian sample of 1562 students aged between 12 and 17 years ( M = 14.83 years, standard deviation = 1.86 years). The Child and Adolescent Perfectionism Scale and the brief 21-item version of the Depression Anxiety Stress Scales were used. Cluster analysis revealed four profiles: Pure Self-Oriented Perfectionism, Pure Socially Prescribed Perfectionism, Mixed Perfectionism, and Non perfectionism. Mixed Perfectionism and Non-perfectionism obtained, respectively, the highest and lowest scores in anxiety, depression, and stress. The results are discussed in light of cultural differences in the interpretation and consequences of perfectionism. PMID- 28984152 TI - DNA barcoding post-larvae can improve the knowledge about fish biodiversity: an example from La Reunion, SW Indian Ocean. AB - The aim of this study was to demonstrate that fish larvae identified using their COI sequences offer a unique opportunity for improving the knowledge of local fish richness. Fish larvae were sampled at the end of their pelagic phase using light-traps set off the West Coast of La Reunion Island, southwestern Indian Ocean, once per month from October 2014 to March 2015. Among the 5174 larvae caught, 214 morphologically different specimens were selected, 196 successfully barcoded, giving a total of 101 different Barcode Index Numbers (BINs). Among these BINs, 55 had never been recorded in La Reunion exclusive economic zone (EEZ), and 13 were new for the BOLD database. Even if the sampling effort for collecting fish post-larvae during this study was relatively low, it allowed adding at least nine new species to an updated checklist of fishes of La Reunion EEZ. PMID- 28984153 TI - Narrow-band UV-B phototherapy: an effective and reliable treatment alternative for extensive and recurrent pityriasis versicolor. AB - PURPOSE: In the previous studies, positive effect of sunlight on seborrheic dermatitis may well be explained by the direct influence of UV-light on the yeasts. Narrow-band ultraviolet-B phototherapy appears to be a very effective and safe treatment option for patients with severe seborrheic dermatitis. We aimed to investigate the efficacy of narrow-band ultraviolet-B phototherapy as an alternative treatment for pityriasis versicolor. MATERIAL AND METHODS: A total of 38 patients diagnosed with disseminated pityriasis versicolor having more than four relapsing episodes within 12 months were treated with narrow-band ultraviolet-B phototherapy given three times weekly. Clinical assessment on the basis of the severity of pruritus, erythema/hyperpigmentation and scaling and mycological examination were made at Weeks 0, 4, 8, 12 and 16. RESULTS: Of the remaining 30 patients, 20 (66.7%) achieved excellent results and four patients (14%) had mild residual disease. The decrease in the clinical scores calculated at 4th week, 8th week, 12th week and 16th week were statistically significant. CONCLUSION: Narrow-band ultraviolet-B presumably may have an immunomodulatory and inhibitory effect on Malassezia growth. Narrowband ultraviolet-B is an effective and safe alternative tool for the management of extensive and recurrent pityriasis versicolor for patients who are unresponsive to conventional treatments. PMID- 28984154 TI - The expression profile and clinicopathological significance of Notch1 in patients with colorectal cancer: a meta-analysis. AB - AIM: This meta-analysis was conducted to evaluate the clinicopathological significance of Notch1 expression in patients with colorectal cancer (CRC). METHODS: Available articles were searched from diverse databases, and the meta analysis was done by using Stata 12.0 software. RESULTS: Thirteen studies were included in this analysis (3401 samples). The Notch1 expression in CRC tissues was significantly higher than that in normal tissues statistically (OR: 15.46; 95% CI: 8.11-29.45; p = 0.003), and were associated with lymph node metastasis, tumor stage, depth of infiltration and histological differentiation. DISCUSSION: There is a close relationship between higher Notch1 expression in CRC. Notch1 may be involved in tumor progression, invasion and metastasis with CRC. CONCLUSION: Notch1 overexpression in CRC suggested aggressive biological behaviors and thus implying that Notch1 may be a useful biomarker in CRCs. PMID- 28984155 TI - Cancer-directed therapy and potential impact on survivals in nonresected hepatocellular carcinoma: SEER-Medicare population study. AB - AIM: To investigate determinants of receiving cancer-directed therapies and their potential survival impact in nonresected hepatocellular carcinoma (HCC) Materials & methods: Nonsurgically resected HCC patients between 2000 and 2010 were stratified by American Joint Committee on Cancer staging and the type of therapy. Predictors of receiving therapy were identified and implication on survival was evaluated. RESULTS: Out of 9239 patients included, those receiving any therapy demonstrated prolonged overall survival with following median overall survival (months): ablation (30.8), Yttrium-90 (15.6), transcatheter arterial chemoembolization (15.5), Sorafenib (5.6), versus no cancer-directed therapy (3.7; p-values <0.001). Overall, 36% of patients received cancer-directed therapy including 47% with stage I/II. Favorable sociodemographic factors predicted receipt of percutaneous locoregional therapies (p-values <0.05). DISCUSSION & CONCLUSION: There appears to be significant disparity in care of nonresected HCC patients with significant underutilization of cancer-directed therapies. PMID- 28984156 TI - Influence of leadership on implementing Dementia Care Mapping: A multiple case study. AB - Dementia Care Mapping is an internationally applied method for enhancing person centred care for people with dementia in nursing homes. Recent studies indicate that leadership is crucial for the successful implementation of Dementia Care Mapping; however, research on this topic is rare. This case study aimed to explore the influence of leadership on Dementia Care Mapping implementation in four nursing homes. Twenty-eight interviews with project coordinators, head nurses and staff nurses were analysed using qualitative content analysis. Nursing homes that failed to implement Dementia Care Mapping were characterised by a lack of leadership. The leaders of successful nursing homes promoted person-centred care and were actively involved in implementation. While overall leadership performance was positive in one of the successful nursing homes, conflicts related to leadership style occurred in the other successful nursing homes. Thus, it is important that leaders promote person-centred care in general and Dementia Care Mapping in particular. Furthermore, different types of leadership can promote successful implementation. Trial registration of the primary study: Current Controlled Trials ISRCTN43916381. PMID- 28984157 TI - The role of therapist support on effectiveness of an internet-based modular self help intervention for adjustment disorder: a randomized controlled trial. AB - BACKGROUND: Adjustment disorder is among the most often diagnosed mental health disorders. Still, there is a lack of specific interventions available for adjustment disorder. OBJECTIVES: The aim of this study was to test if an internet based self-help intervention for adjustment disorder could be effective without therapist involvement. DESIGN: A parallel group randomized controlled trial design was used to test the effectiveness of the Brief Adjustment Disorder Intervention (BADI) - an internet-based intervention for adjustment disorder. METHODS: In total 1077 participants were randomized into two conditions: BADI intervention and BADI intervention with therapist support. The main outcome measures were symptoms of adjustment disorder and well-being. RESULTS: Pre intervention to post-intervention adjustment disorder effect size for the BADI intervention group was d = 0.64, and for the BADI with therapist support group the effect size was d = 0.53. CONCLUSIONS: The present study supported the effectiveness of the BADI intervention. Our findings also indicated that adding therapist support to the standard BADI intervention did not significantly improve the outcomes. PMID- 28984158 TI - Magnitude and sources of distress in mid-life adults with chronic medical illness: an exploratory mixed-methods analysis. AB - Most mid-life adults have at least one chronic medical condition (CMC) and are at risk for developing additional CMCs. Stressors specific to this life stage may contribute to CMC development by hindering healthy behaviors. The goal of this study was to compare sources and intensity of distress, as they relate to health behaviors, between mid-life and non-mid-life adults with CMCs. We utilized a mixed-methods approach by analyzing quantitative self-report measures of psychiatric symptoms and psychological well-being, with in-depth, semi-structured qualitative interviews to identify sources of stress in three cohorts of patients with CMCs (heart failure, type 2 diabetes, and coronary artery disease). Between group differences on self-report measures were compared via independent samples t tests and relevant themes from interview transcripts were compared via chi-square analysis. We found that mid-life participants (n = 30) reported greater psychological distress (depression/anxiety) than non-mid-life (n = 62) participants (Hospital Anxiety and Depression Scale scores 13.8 [SD 7.3] vs. 10.6 [SD 6.6]; t(90)=2.13; p = .035), and qualitative analysis revealed several specific sources of stress significantly more common (p < .001) in mid-life adults. Interventions targeting the needs of this population could reduce distress, improve health behaviors, and have a major impact on public health. PMID- 28984159 TI - Longer term effectiveness of inpatient multidisciplinary rehabilitation on health related quality of life in MS patients: a pragmatic randomized controlled trial - The Danish MS Hospitals Rehabilitation Study. AB - BACKGROUND: There is insufficient evidence to support the effectiveness of multidisciplinary rehabilitation on the health-related quality of life (HRQoL) of MS patients. OBJECTIVES: To evaluate the longer term effectiveness of inpatient multidisciplinary rehabilitation on the HRQoL of MS patients. METHODS: The study was a two-hospital, pragmatic, randomized controlled trial with a 6-month follow up. Patients aged 18-65 years with MS and Expanded Disability Status Scale scores <=7.5 were randomly assigned (1:1) to 4 weeks of inpatient multidisciplinary rehabilitation (20 days of scheduled rehabilitation) or 6 months on a wait list. The outcome measures were Functional Assessment in Multiple Sclerosis (FAMS), Multiple Sclerosis Impact Scale-29 (MSIS-29), EQ-5D-5L and 15D. RESULTS: We randomized 213 patients to the wait-list control group and 214 patients to the treatment group. Trends in favour of the treatment group were observed across all measures. However, the difference was significant in only two of the six measures. The treatment effect was -2.7 (95% CI: -5.6 to (-0.1)), p = 0.046) for the MSIS-29 Psychological and 0.017 (95% CI: 0.005-0.030, p = 0.008) for the 15D. FAMS, which we used to calculate the sample size, was not significant. CONCLUSION: The results indicated that inpatient multidisciplinary rehabilitation is effective in improving the HRQoL of MS patients after 6 months. PMID- 28984160 TI - R-lipoic acid overdosing affects platelet life span via ROS mediated autophagy. AB - R-lipoic acid (ALA), a powerful antioxidant valuable for the treatment of diabetes and its complications, has been reported to exhibit an antiplatelet activity in vitro. The aim of this study was to investigate the effect and mechanism of ALA on platelets in vivo. Sprague-Dawley (SD) male rats were intravenously administered with low-dose ALA (20 mg/kg/d), high-dose ALA (80 mg/kg/d) and saline, respectively. Platelets count and bone marrow smear were evaluated and the expressions of markers related to apoptosis and autophagy were measured. Platelet clearance analysis was conducted out on mice. The results showed that high-dose ALA administration could significantly decrease platelet count by 43% compared with control group, whereas, megakaryocytes showed no difference in the number. Moreover, high-dose ALA administration led to significant reduction in half-life of circulating platelets, indicative of enhanced rate of platelet clearance. Interesting, high-dose ALA administration could increase the level of reactive oxygen species (ROS) in platelets and induce autophagy without affecting apoptosis. Our finding also showed that high ALA induced autophagy in platelets was mediated by class III PtdIns3K activity, which could be reversed by 3-methyladenine (3-MA). Moreover, AKT and MAPK/ERK pathways were also observed to be involved in the regulation of autophagy in platelets. Thus, high-dose ALA could induce autophagy in platelets through modulating the activity of class III PtdIns3K, which was associated with decreased count of circulating platelets and shortened lifespan of platelets. PMID- 28984161 TI - Teaching feedback: An unregulated currency in medical education. PMID- 28984163 TI - Epidemiology of NMOSD in Catalonia: Influence of the new 2015 criteria in incidence and prevalence estimates. AB - BACKGROUND: Population-based studies on neuromyelitis optica spectrum disorders (NMOSD) are limited, and it is unclear whether the rates have changed with the implementation of the new 2015 criteria. OBJECTIVES: To estimate the incidence and prevalence of NMOSD in Catalonia (Spain), using both the 2006 and the 2015 criteria. METHODS: In this clinic-based retrospective study, patients diagnosed with NMOSD between 2006 and 2015 were identified using multiple sources, including direct contact to all Catalan hospitals, identification of cases through the Catalan Health Surveillance System, and registry of antibodies to aquaporin-4 (AQP4-IgG) and myelin oligodendrocyte glycoprotein (MOG-IgG) in a reference laboratory. The incidence rate was calculated for the period 1 January 2006-1 January 2016 and prevalence for the date 1 January 2016. RESULTS: We identified 74 patients (by the 2015 criteria). Most patients were Caucasian (81%), and female (76%) with a median age at disease onset of 42 years (range, 10 76 years). In total, 54 (73%) patients were positive for AQP4-IgG, 11 (15%) double-seronegative, and 9 (12%) MOG-IgG-positive. Rates of incidence and prevalence (0.63/1,000,000 person-years and 0.89/100,000, respectively) were 1.5 fold higher than those reported by the 2006 criteria. Lowest rates were seen in children and elder people and highest in women and middle-aged people (40-59 years). The female predominance was lost in incident AQP4-IgG-seronegative children and AQP4-IgG-positive elder people. MOG-IgG and double-seronegativity contributed similarly but did not influence the long-term outcome. CONCLUSION: The new criteria increase the estimates, but NMOSD remains as a rare disease. The differences in age- and sex-specific estimates highlight the importance of the serologic classification. PMID- 28984164 TI - Promoting synergistic partnerships in low resource countries: a case study exemplar. AB - OBJECTIVES/AIMS: The purpose of this discussion is to explore the dynamics of partnership and its impact on both nursing faculty at Hue University of Medicine and Pharmacy (HueUMP) and Health Volunteers Overseas (HVO) volunteers. DESIGN: A case study approach was used to promote understanding of partnerships in global health. DISCUSSION: Collaboration between HueUMP's nursing program and HVO is one of the most dynamic HVO nurse educator programs with five volunteer visits to Vietnam within a two-year period. Volunteer efforts include workshops to meet the diverse needs and interests of nursng faculty. We also emphasize the potential for ongoing strategic program planning integrating components from other nursing partnerships in the Southeast Asian region. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: If we are to continue meeting partnership goals, we must recognize that partnerships should evolve according to the goals of HueUMP nursing faculty and the context of nursing in Vietnam. PMID- 28984162 TI - Acid-base regulation and sensing: Accelerators and brakes in metabolic regulation of cerebrovascular tone. AB - Metabolic regulation of cerebrovascular tone directs blood flow to areas of increased neuronal activity and during disease states partially compensates for insufficient perfusion by enhancing blood flow in collateral blood vessels. Acid base disturbances frequently occur as result of enhanced metabolism or insufficient blood supply, but despite definitive evidence that acid-base disturbances alter arterial tone, effects of individual acid-base equivalents and the underlying signaling mechanisms are still being debated. H+ is an important intra- and extracellular messenger that modifies cerebrovascular tone. In addition, low extracellular [HCO3-] promotes cerebrovascular contraction through an endothelium-dependent mechanism. CO2 alters arterial tone development via changes in intra- and extracellular pH but it is still controversial whether CO2 also has direct vasomotor effects. Vasocontractile responses to low extracellular [HCO3-] and acute CO2-induced decreases in intracellular pH can counteract H+ mediated vasorelaxation during metabolic and respiratory acidosis, respectively, and may thereby reduce the risk of capillary damage and cerebral edema that could be consequences of unopposed vasodilation. In this review, the signaling mechanisms for acid-base equivalents in cerebral arteries and the mechanisms of intracellular pH control in the arterial wall are discussed in the context of metabolic regulation of cerebrovascular tone and local perfusion. PMID- 28984165 TI - Target definition in salvage postoperative radiotherapy for prostate cancer: 18F fluorocholine PET/CT assessment of local recurrence. AB - PURPOSE: Inadequate clinical target volume (CTV) definition is likely to be a major contributing factor to local recurrence (LR) rate after radiotherapy. Our aims were to identify sites of prostate cancer LR in biochemical recurrence post prostatectomy using 18F-Fluorocholine (18F-FCH) positron emission tomography/computed tomography (PET/CT) and to compare different CTV-delineation guidelines in a cohort of postoperative patients. MATERIAL AND METHODS: Thirty six patients presenting with LR within the prostatic bed on 18F-FCH PET/CT between 10/2011 and 06/2016 were included in this retrospective study. Median PSA at the time of 18F-FCH PET/CT was 2.7 ng/mL (0.8-9.4) and median PSA doubling time was 11 months (3-28). For each patient, the CTVRTOG, CTVFROGG and CTVEORTC following the corresponding guidelines were outlined and compared. Forty-one LR were delineated using a gradient-based method and the percentage of FCH uptake included in each CTV was evaluated. RESULTS: The anastomosis was the most common recurrence site (52.8%), followed by the retrovesical region (31.7%) and the bladder neck (7%). The median SUV max value was 4.8 (2.3-16.1). The percentage of LR entirely included in the CTVRTOG was not significantly different from that included in the CTVFROGG (84% versus 83%, p = .5). Significantly more recurrences were included in the CTVRTOG volume compared to the CTVEORTC (84% versus 68%, p=.006), due to a better coverage of the bladder neck and retrovesical regions. Six out of 10 relapses occurring in the posterior region of the anastomosis were not covered by any of the CTVs. CONCLUSIONS: In our study, the CTVRTOG and CTVFROGG ensured the best coverage of LR seen on 18F-FCH PET/CT. When outlining the prostatic fossa, greater coverage of the posterior vesico-urethral region may allow better coverage of potential microscopic disease. PMID- 28984166 TI - Dual action by fumaric acid esters synergistically reduces adhesion to human endothelium. AB - OBJECTIVE: Dimethyl fumarate (DMF) is prescribed against relapsing-remitting multiple sclerosis (MS). Here, we investigated the effects of DMF and monomethyl fumarate (MMF), its metabolite in vivo, at the (inflamed) blood-brain barrier (BBB). METHODS: Effects of fumaric acid esters were analyzed using primary human brain-derived microvascular endothelial cells (HBMECs) in combination with peripheral blood mononuclear cells (PBMCs) derived from DMF-treated MS patients. RESULTS: MMF-binding to brain endothelium cells leads to activation of nuclear factor (erythroid-derived 2)-related factor 2 (Nrf2)-induced downregulation of vascular cell adhesion molecule 1 (VCAM-1). This might be mediated via the G protein-coupled receptor (GPCR) hydroxycarboxylic acid receptor 2 (HCA2), a known molecular target of MMF, as we could demonstrate its expression and regulation on HBMECs. DMF treatment in vivo led to a strongly reduced expression of VCAM-1's ligand very late antigen 4 (VLA-4) by selectively reducing integrin high expressing memory T cells of MS patients, potentially due to inhibition of their maturation by reduced trans-localization of NFkappaB. CONCLUSION: DMF-mediated VCAM-1 downregulation on the endothelial side and reduction in T cells with a migratory phenotype on the lymphocyte side result in a synergistic reduction in T cell adhesion to activated endothelium and, therefore, to reduced BBB transmigration in the setting of MS. PMID- 28984167 TI - Task-Related Phasing of Circadian Rhythms in Antennal Responsiveness to Odorants and Pheromones in Honeybees. AB - The insect antennae receive olfactory information from the environment. In some insects, it has been shown that antennal responsiveness is dynamically regulated by circadian clocks. However, it is unknown how general this phenomenon is and what functions it serves. Circadian regulation in honeybee workers is particularly interesting in this regard because they show natural task-related chronobiological plasticity. Forager bees show strong circadian rhythms in behavior and brain gene expression, whereas nurse bees tend brood around-the clock and have attenuated circadian rhythms in activity and whole-brain gene expression. Here, we tested the hypothesis that there is task-related plasticity in circadian rhythms of antennal responsiveness to odorants in worker honeybees. We used electroantennogram (EAG) to measure the antennal responsiveness of nurses and foragers to general odorants and pheromones around the day. The capacity to track 10-Hz odorant pulses varied with time of day for both task groups but with different phases. The antennal pulse-tracking capacity was higher during the subjective day for the day-active foragers, whereas it was better during the night for around-the-clock active nurses. The task-related phases of pulse tracking rhythms were similar for all the tested stimuli. We also found evidence for circadian rhythms in the EAG response magnitude of foragers but not of nurses. To the best of our knowledge, these results provide the first evidence for circadian regulation of antennal olfactory responsiveness and odorant pulse tracking capacity in bees or any other hymenopteran insect. Importantly, our study shows for the first time that the circadian phase of olfactory responsiveness may be socially regulated. PMID- 28984169 TI - The relationship among resilience, rumination and posttraumatic growth in hemodialysis patients in North China. AB - Research has indicated that clinical serious disease may lead to posttraumatic growth (PTG). However, little is known about PTG among hemodialysis (HD) patients. The study examined the relationship among resilience, rumination and PTG among Chinese HD patients. 196 HD patients were recruited from a tertiary hospital in a Northern city of China between 1 June 2015 and 30 May 2016. Patients were surveyed using the Posttraumatic Growth Inventory-Chinese version, Connor-Davidson Resilience Scale, and Chinese Event Related Rumination Inventory. Correlation analyses showed that resilience was most highly positively correlated with PTG (r = .70, p < .001), deliberate rumination moderately correlated to PTG (r = .50, p < .001), and intrusive rumination was lower negatively related to PTG (r = -.26, p < .001). Regression analyses showed that age, gender, duration of dialysis, resilience and deliberate rumination had significant associations with PTG (beta = -.31, p < .0001; beta = -.14, p = .002; beta = .10, p = .032; beta = .44, p < .001; beta = .20, p < .001). They together explained 65% of the total variance in PTG (F [8,195] = 46.74, p < .001). However, intrusive rumination was not associated with PTG (p > .05). The results suggested that resilience and deliberate rumination may be instrumental for PTG improvement. PMID- 28984168 TI - Perceptions of Equipoise, Risk-Benefit Ratios, and "Otherwise Healthy Volunteers" in the Context of Early-Phase HIV Cure Research in the United States: A Qualitative Inquiry. AB - Early-phase HIV cure research is conducted against a background of highly effective antiretroviral therapy, and involves risky interventions in individuals who enjoy an almost normal life expectancy. To explore perceptions of three ethical topics in the context of HIV cure research-(a) equipoise, (b) risk benefit ratios, and (c) "otherwise healthy volunteers"-we conducted 36 in-depth interviews (IDIs) with three groups of purposively selected key informants: clinician-researchers ( n = 11), policy-makers and bioethicists ( n = 13), and people living with HIV (PLWHIV; n = 12). Our analysis revealed variability in perceptions of equipoise. Second, most key informants believed there was no clear measure of risk-benefit ratios in HIV cure research, due in part to the complexity of weighing (sometimes unknown) risks to participants and (sometimes speculative) benefits to science and society. Third, most clinician-researchers and policy-makers/bioethicists viewed potential HIV cure study participants as "otherwise healthy volunteers," but this perception was not shared among PLWHIV in our study. PMID- 28984170 TI - Perceived sources and levels of stress, general self-efficacy and coping strategies in preclinical dental students. AB - Dental education programs are known to be highly stressful and stress can affect general health. The aims were to identify sources of stress among preclinical students and to evaluate their perceived levels of stress, self-efficacy and effective coping strategies in a private dental school. One hundred preclinical students in a Turkish private dental school were surveyed using dental environment stress (DES), perceived stress (PSS), general self-efficacy (G-SES) and brief coping scales (Brief-COPE). Age, gender, history of psychiatric treatment, factors that affected the choice of dentistry, choice rank of dental school, scholarship and income was recorded. 'Exams and grades' followed by 'Fear of failing course or year' were found to be the most stressprovoking factors. The most and the least stressprovoking DES domains were 'Workload' and 'Social stressors', respectively. 'Social stressors' affected male more than female (p < .05). The most and the least common coping strategies were found to be 'Planning', and 'Drug', respectively. Female used 'Instrumental support' more than male (p < .05). Demographic factors had impact on the perceived stress factors and levels, as well as coping strategies. Unlike previous studies establishing high stress levels in dental students, preclinical students displayed moderate level of stress. Clinical dental education might be more responsible for creating stress. PMID- 28984171 TI - Aberrant sylvian vein: A newly described cause of pulsatile tinnitus. AB - We herein report a newly described cause of venous pulsatile tinnitus: protrusion of an aberrant sylvian vein into the tympanum. A 60-year-old woman presented with a 4-month history of objective persistent pulsatile tinnitus in the right ear with no other complaints. The pulsatile tinnitus diminished with rotation of the head to the right side or by compression of the right cervical vascular structures. The frequency and intensity of the tinnitus were 125 Hz and 20 dB HL, respectively. Audiometry and otoscopic examination findings were normal. Radiologic examination showed that the right sylvian vein protruded into the tympanum through the dehiscent anterior cortical plate of the tympanum. PMID- 28984172 TI - Analysis of mortality in the emergency department at a university hospital in Pleven. AB - Objective To identify the demographic patterns of mortality, the time spent before death in the emergency department (ED), and the causes of fatal outcomes. Methods We performed a 5-year (01/01/2011 to 01/01/2016) retrospective analysis of all non-traumatic deaths in the ED of the UMHAT - Pleven. To extract the necessary information, we used the registers in the ED until the patients' death. Results Among 156,848 patients in the study period, 381 died and the mortality rate was 2.4/100000. The male:female ratio was 1.48:1. The 71-80 years age group was the most affected. The mean (SD) age of patients who died in the ED was 69.9 +/- 8.4 years. Most non-traumatic deaths (222 cases) were due to cardiovascular disease. Most patients (70.9%) died within 2.3 h after arrival. The factors contributing to mortality included poverty, transporting the patient to hospital too late, and a lack of developed care centres for terminally ill patients. Conclusion Most patients die within approximately 2 h after arrival at the ED. The main cause of death is acute myocardial infarction. Pulmonary embolism remains unrecognized in most patients (69%). Oncological pathology is among the main causes (7.4%) of mortality. PMID- 28984173 TI - Facilitators and barriers to referral compliance among dental patients with increased risk of obstructive sleep apnea. AB - OBJECTIVE: Our aims were to determine the adherence rate to dentist referrals for sleep apnea evaluation and the barriers and facilitators to referral compliance. MATERIAL AND METHODS: A sample of 1099 patients was screened with the STOP-Bang questionnaire. Those with elevated risk were referred for a sleep evaluation. An interview was conducted over the phone to determine compliance to referral and the barriers and facilitators to compliance. RESULTS: Of the 1099 patients (mean age: 45.1 +/- 10 years) screened, 224 (20.4%) patients were determined to be at risk for obstructive sleep apnea (OSA). Only 41 (18.3%) patients with increased risk adhered to referral recommendation. Demographic and health characteristics did not show significant differences between the compliant and non-compliant patients. The most common facilitators to compliance were increased awareness about OSA (N = 25, 65%) and dentist recommendation (N = 14, 34.1%), whereas the most common barriers to referral compliance were misconceptions about OSA (N = 69, 37.7%) and work responsibilities (N = 44, 24%). CONCLUSIONS: Only a small percentage of patients adhered to the recommendation of their dentist to see a sleep specialist. Increased awareness about OSA and dentist recommendation were the most common factors that facilitated compliance, whereas misconceptions about OSA and work responsibilities were the most common barriers to patient compliance. PMID- 28984174 TI - The effect of menopause on the relationship between hyperlipidemia and periodontal disease via salivary 8-hydroxy-2'-deoxyguanosine and myeloperoxidase levels. AB - OBJECTIVE: Impairment of the lipid metabolism could affect the periodontal disease; increased oxidative stress may have a role in this relationship. The aim of the present study was to evaluate the role of menopause in the relationship between hyperlipidemia and periodontal disease via oxidative stress markers in saliva. MATERIALS AND METHODS: Sixty-seven women were enrolled in the study and divided into four groups as systemically healthy and premenopause (C) (n = 18), hyperlipidemia and premenopause (H) (n = 16), systemically healthy and postmenopause (M) (n = 17), and hyperlipidemia and postmenopause (MH) (n = 16). Sociodemographics, periodontal and metabolic parameters, and saliva oxidative markers (myeloperoxidase [MPO] and 8-hydroxy-2'-deoxyguanosine [8-OHdG]) were evaluated. RESULTS: Menopause and/or hyperlipidemia were associated with an increase in all evaluated periodontal parameters. Saliva 8-OHdG and MPO levels were higher in menopausal groups (M and MH). Multivariate linear regression analyses revealed that hyperlipidemia was related to an increase in periodontal parameters. Salivary oxidative stress markers and periodontal parameters were also positively associated with menopause and hyperlipidemia. CONCLUSION: Saliva 8-OHdG and MPO levels may indicate that the relationship between periodontal disease and hyperlipidemia is aggravated by menopause. PMID- 28984175 TI - Primary central nervous system lymphoma: Retrospective analysis of 34 cases in a single centre. AB - Objective To retrospectively analyse outcomes in patients with primary central nervous system lymphoma (PCNSL), which is a malignant CNS non-Hodgkin's lymphoma with a poor prognosis. Methods This study retrospectively analysed the treatment and outcomes of patients with PCNSL, which were divided into two groups: surgery (S) group and surgery/biopsy+chemotherapy (SC) group. The latter group was further subdivided into four cohorts based on the treatment regimen: cyclophosphamide, epidoxorubicin, vincristine and prednisone (CHOP), high-dose methotrexate (HDM)+dexamethasone+rituximab (HDM+D+R), HDM+D+temozolomide (HDM+D+T), and HDM+D+R+T. Results The study enrolled 34 patients; 10 of which received surgery only. Between the S and SC groups, the median progression-free survival (PFS) and overall survival (OS) of intracranial PCNSLs ( n = 32) were 8.5 months versus 29 months, respectively; and 8.5 months versus 54 months, respectively (5-year OS: 10.0% versus 48.7%, respectively; 2-year PFS: 0.0% versus 52.6%, respectively). Comparing the CHOP and HDM-based chemotherapy cohorts, the median PFS and OS were 15 months versus not achieved, respectively, and 25 months versus not achieved, respectively (5-year OS: 20.0% versus 60.8%, respectively; 2-year PFS: 20.0% versus 62.7%, respectively). Conclusion Chemotherapy appears to provide a better OS and PFS for patients with PCNSLs compared with surgery alone. HDM+D+T and HDM+D+R+T may be effective choices for PCNSL treatment. PMID- 28984176 TI - Detection of vulnerable atherosclerotic plaque during thoracic endovascular aortic repair using nonobstructive angioscopy. AB - An angioscope was used to observe the intima of the aorta in an 82-year-old patient who had undergone thoracic endovascular aortic repair. The aortic angioscopic findings showed vulnerable plaques from the ascending aorta to the aortic arch that had not been visualized using preoperative computed tomography. After deploying a stent graft from zone 1 to zone 4, the proximal edge of the stent graft was adjacent to the ruptured plaque with mixed thrombi. In spite of these findings, the patient had an uneventful recovery. Angioscopy may have the potential to stratify the risk of thoracic endovascular aortic repair-related complications. PMID- 28984177 TI - Effect of Tai Chi Chuan on degeneration of lumbar vertebrae and lumbar discs in middle-aged and aged people: a cross-sectional study based on magnetic resonance images. AB - Objective Exercise has a positive effect on physical fitness. Tai Chi Chuan is a traditional Chinese aerobic exercise. We assessed the effect of Tai Chi on the degeneration of lumbar vertebrae and lumbar discs with magnetic resonance images. Methods This retrospective cohort study involved 2 groups of participants: 27 Tai Chi practitioners with more than 4 years of experience with regular Tai Chi exercise and 24 sex- and age-matched participants without Tai Chi experience. The lumbar magnetic resonance images of all participants were collected. The numbers of degenerated lumbar vertebrae and lumbar discs were evaluated by the same radiologist, who was blind to the grouping. Results The Tai Chi practitioners had significantly fewer degenerated lumbar vertebrae (1.9) and lumbar discs (2.3) than the control group (2.6 and 2.9, respectively). The most severely affected lumbar vertebrae and discs were L5 and L4/L5, respectively. Conclusion Regular performance of the simplified Tai Chi 24 form could possibly retard the degeneration of lumbar vertebrae and lumbar discs in middle-aged and aged people. PMID- 28984179 TI - Efficacy of daclizumab beta versus intramuscular interferon beta-1a on disability progression across patient demographic and disease activity subgroups in DECIDE. AB - BACKGROUND: Demonstration of clinical benefits on disability progression measures is an important attribute of effective multiple sclerosis (MS) treatments. OBJECTIVE: Examine efficacy of daclizumab beta versus intramuscular (IM) interferon beta-1a on measures of disability progression in patient subgroups from DECIDE. METHODS: Twenty-four-week confirmed disability progression (CDP), 24 week sustained worsening on a modified Multiple Sclerosis Functional Composite (MSFCS) where 3-Second Paced Auditory Serial Addition Test was replaced by Symbol Digit Modalities Test, and proportion of patients with clinically meaningful worsening in 29-Item Multiple Sclerosis Impact Scale physical impact subscale (MSIS-29 PHYS) score from baseline to week 96 were examined in the overall population and subgroups defined by baseline demographic/disease characteristics. RESULTS: Daclizumab beta significantly reduced risk of 24-week CDP (hazard ratio (HR), 0.73; 95% confidence interval (95% CI), 0.55-0.98), risk of 24-week sustained MSFCS progression (HR, 0.80; 95% CI, 0.67-0.95), and odds of clinically meaningful worsening in MSIS-29 PHYS (odds ratio, 0.76; 95% CI, 0.60-0.95) versus IM interferon beta-1a. Point estimates showed trends favoring daclizumab beta over IM interferon beta-1a across several patient subgroups for all three outcome measures. CONCLUSION: Daclizumab beta showed consistent benefit versus IM interferon beta-1a across measures assessing patient disability/function and across a range of clinical baseline characteristics in patients with relapsing remitting MS. PMID- 28984178 TI - Effects of donor age on human adipose-derived adherent stromal cells under oxidative stress conditions. AB - Objective Adipose-derived stromal vascular fractions (SVFs) are heterogeneous complex populations of cells with therapeutic efficacy for tissue generation and vascular stabilization. SVFs have cardiomyogenic potential, and many researchers have examined the possibility of SVF transplantation for heart disease. In cell based therapies, donor age affects the regenerative capability, cell yield, and differentiation potential of adult tissues; however, opposing or controversial results have been found in humans. We examined whether SVF transplantation into impaired heart tissue shows differential effects according to donor age. Methods We investigated differences in protein expression in human umbilical vein endothelial cells (HUVECs) co-cultured with adipose-derived adherent stromal cells (ADASs) from donors of different ages [>40-year-olds (40s group) and >60 year-olds (60s group)] under oxidative stress conditions. Results Although co culturing HUVECs with ADASs ameliorated inflammation due to increased oxidative stress conditions, few differences were observed between the ADASs from the 40s and 60s groups. Moreover, the Database for Annotation, Visualization, and Integrated Discovery classification tool revealed differentially expressed genes in the Kyoto Encyclopedia of Genes and Genomes pathway associated with cytokine cytokine receptor interaction in response to ADASs. Conclusion Protein expression profiles were unchanged in HUVECs induced by isolated ADASs from donors of different ages under oxidative stress conditions. PMID- 28984180 TI - CNN-based ranking for biomedical entity normalization. AB - BACKGROUND: Most state-of-the-art biomedical entity normalization systems, such as rule-based systems, merely rely on morphological information of entity mentions, but rarely consider their semantic information. In this paper, we introduce a novel convolutional neural network (CNN) architecture that regards biomedical entity normalization as a ranking problem and benefits from semantic information of biomedical entities. RESULTS: The CNN-based ranking method first generates candidates using handcrafted rules, and then ranks the candidates according to their semantic information modeled by CNN as well as their morphological information. Experiments on two benchmark datasets for biomedical entity normalization show that our proposed CNN-based ranking method outperforms traditional rule-based method with state-of-the-art performance. CONCLUSIONS: We propose a CNN architecture that regards biomedical entity normalization as a ranking problem. Comparison results show that semantic information is beneficial to biomedical entity normalization and can be well combined with morphological information in our CNN architecture for further improvement. PMID- 28984181 TI - Optimal choice of word length when comparing two Markov sequences using a chi 2 statistic. AB - BACKGROUND: Alignment-free sequence comparison using counts of word patterns (grams, k-tuples) has become an active research topic due to the large amount of sequence data from the new sequencing technologies. Genome sequences are frequently modelled by Markov chains and the likelihood ratio test or the corresponding approximate chi 2-statistic has been suggested to compare two sequences. However, it is not known how to best choose the word length k in such studies. RESULTS: We develop an optimal strategy to choose k by maximizing the statistical power of detecting differences between two sequences. Let the orders of the Markov chains for the two sequences be r 1 and r 2, respectively. We show through both simulations and theoretical studies that the optimal k= max(r 1,r 2)+1 for both long sequences and next generation sequencing (NGS) read data. The orders of the Markov chains may be unknown and several methods have been developed to estimate the orders of Markov chains based on both long sequences and NGS reads. We study the power loss of the statistics when the estimated orders are used. It is shown that the power loss is minimal for some of the estimators of the orders of Markov chains. CONCLUSION: Our studies provide guidelines on choosing the optimal word length for the comparison of Markov sequences. PMID- 28984182 TI - Identification of genome-wide non-canonical spliced regions and analysis of biological functions for spliced sequences using Read-Split-Fly. AB - BACKGROUND: It is generally thought that most canonical or non-canonical splicing events involving U2- and U12 spliceosomes occur within nuclear pre-mRNAs. However, the question of whether at least some U12-type splicing occurs in the cytoplasm is still unclear. In recent years next-generation sequencing technologies have revolutionized the field. The "Read-Split-Walk" (RSW) and "Read Split-Run" (RSR) methods were developed to identify genome-wide non-canonical spliced regions including special events occurring in cytoplasm. As the significant amount of genome/transcriptome data such as, Encyclopedia of DNA Elements (ENCODE) project, have been generated, we have advanced a newer more memory-efficient version of the algorithm, "Read-Split-Fly" (RSF), which can detect non-canonical spliced regions with higher sensitivity and improved speed. The RSF algorithm also outputs the spliced sequences for further downstream biological function analysis. RESULTS: We used open access ENCODE project RNA-Seq data to search spliced intron sequences against the U12-type spliced intron sequence database to examine whether some events could occur as potential signatures of U12-type splicing. The check was performed by searching spliced sequences against 5'ss and 3'ss sequences from the well-known orthologous U12 type spliceosomal intron database U12DB. Preliminary results of searching 70 ENCODE samples indicated that the presence of 5'ss with U12-type signature is more frequent than U2-type and prevalent in non-canonical junctions reported by RSF. The selected spliced sequences have also been further studied using miRBase to elucidate their functionality. Preliminary results from 70 samples of ENCODE datasets show that several miRNAs are prevalent in studied ENCODE samples. Two of these are associated with many diseases as suggested in the literature. Specifically, hsa-miR-1273 and hsa-miR-548 are associated with many diseases and cancers. CONCLUSIONS: Our RSF pipeline is able to detect many possible junctions (especially those with a high RPKM) with very high overall accuracy and relative high accuracy for novel junctions. We have incorporated useful parameter features into the pipeline such as, handling variable-length read data, and searching spliced sequences for splicing signatures and miRNA events. We suggest RSF, a tool for identifying novel splicing events, is applicable to study a range of diseases across biological systems under different experimental conditions. PMID- 28984183 TI - XBSeq2: a fast and accurate quantification of differential expression and differential polyadenylation. AB - BACKGROUND: RNA sequencing (RNA-seq) is a high throughput technology that profiles gene expression in a genome-wide manner. RNA-seq has been mainly used for testing differential expression (DE) of transcripts between two conditions and has recently been used for testing differential alternative polyadenylation (APA). In the past, many algorithms have been developed for detecting differentially expressed genes (DEGs) from RNA-seq experiments, including the one we developed, XBSeq, which paid special attention to the context-specific background noise that is ignored in conventional gene expression quantification and DE analysis of RNA-seq data. RESULTS: We present several major updates in XBSeq2, including alternative statistical testing and parameter estimation method for detecting DEGs, capacity to directly process alignment files and methods for testing differential APA usage. We evaluated the performance of XBSeq2 against several other methods by using simulated datasets in terms of area under the receiver operating characteristic (ROC) curve (AUC), number of false discoveries and statistical power. We also benchmarked different methods concerning execution time and computational memory consumed. Finally, we demonstrated the functionality of XBSeq2 by using a set of in-house generated clear cell renal carcinoma (ccRCC) samples. CONCLUSIONS: We present several major updates to XBSeq. By using simulated datasets, we demonstrated that, overall, XBSeq2 performs equally well as XBSeq in terms of several statistical metrics and both perform better than DESeq2 and edgeR. In addition, XBSeq2 is faster in speed and consumes much less computational memory compared to XBSeq, allowing users to evaluate differential expression and APA events in parallel. XBSeq2 is available from Bioconductor: http://bioconductor.org/packages/XBSeq/. PMID- 28984185 TI - STRScan: targeted profiling of short tandem repeats in whole-genome sequencing data. AB - BACKGROUND: Short tandem repeats (STRs) are found in many prokaryotic and eukaryotic genomes, and are commonly used as genetic markers, in particular for identity and parental testing in DNA forensics. The unstable expansion of some STRs was associated with various genetic disorders (e.g., the Huntington disease), and thus was used in genetic testing for screening individuals at high risk. Traditional STR analyses were based on the PCR amplification of STR loci followed by gel electrophoresis. With the availability of massive whole genome sequencing data, it becomes practical to mine STR profiles in silico from genome sequences. Software tools such as lobSTR and STR-FM have been developed to address these demands, which are, however, built upon whole genome reads mapping tools, and thus may not be sensitive enough. RESULTS: In this paper, we present a standalone software tool STRScan that uses a greedy algorithm for targeted STR profiling in next-generation sequencing (NGS) data. STRScan was tested on the whole genome sequencing data from Venter genome sequencing and 1000 Genomes Project. The results showed that STRScan can profile 20% more STRs in the target set that are missed by lobSTR. CONCLUSION: STRScan is particularly useful for the NGS-based targeted STR profiling, e.g., in genetic and human identity testing. STRScan is available as open-source software at http://darwin.informatics.indiana.edu/str/ . PMID- 28984184 TI - Using machine learning algorithms to identify genes essential for cell survival. AB - BACKGROUND: With the explosion of data comes a proportional opportunity to identify novel knowledge with the potential for application in targeted therapies. In spite of this huge amounts of data, the solutions to treating complex disease is elusive. One reason being that these diseases are driven by a network of genes that need to be targeted in order to understand and treat them effectively. Part of the solution lies in mining and integrating information from various disciplines. Here we propose a machine learning method to mining through publicly available literature on RNA interference with the goal of identifying genes essential for cell survival. RESULTS: A total of 32,164 RNA interference abstracts were identified from 10.5 million pubmed abstracts (2001 - 2015). These abstracts spanned over 1467 cancer cell lines and 4373 genes representing a total of 25,891 cell gene associations. Among the 1467 cell lines 88% of them had at least 1 or up to 25 genes studied in a given cell line. Among the 4373 genes 96% of them were studied in at least 1 or up to 25 different cell lines. CONCLUSIONS: Identifying genes that are crucial for cell survival can be a critical piece of information especially in treating complex diseases, such as cancer. The efficacy of a therapeutic intervention is multifactorial in nature and in many cases the source of therapeutic disruption could be from an unsuspected source. Machine learning algorithms helps to narrow down the search and provides information about essential genes in different cancer types. It also provides the building blocks to generate a network of interconnected genes and processes. The information thus gained can be used to generate hypothesis which can be experimentally validated to improve our understanding of what triggers and maintains the growth of cancerous cells. PMID- 28984186 TI - PennCNV in whole-genome sequencing data. AB - BACKGROUND: The use of high-throughput sequencing data has improved the results of genomic analysis due to the resolution of mapping algorithms. Although several tools for copy-number variation calling in whole genome sequencing have been published, the noisy nature of sequencing data is still a limitation for accuracy and concordance among such tools. To assess the performance of PennCNV original algorithm for array data in whole genome sequencing data, we processed mapping (BAM) files to extract coverage, representing log R ratio (LRR) of signal intensity, and B allele frequency (BAF). RESULTS: We used high quality sample NA12878 from the recently reported NIST database and created 10 artificial samples with several CNVs spread along all chromosomes. We compared PennCNV-Seq with other tools with general deletions and duplications, as well as for different number of copies and copy-neutral loss-of-heterozygosity (LOH). CONCLUSION: PennCNV-Seq was able to find correct CNVs and can be integrated in existing CNV calling pipelines to report accurately the number of copies in specific genomic regions. PMID- 28984187 TI - New statistical methods for estimation of recombination fractions in F2 population. AB - BACKGROUND: Dominant markers in an F2 population or a hybrid population have much less linkage information in repulsion phase than in coupling phase. Linkage analysis produces two separate complementary marker linkage maps that have little use in disease association analysis and breeding. There is a need to develop efficient statistical methods and computational algorithms to construct or merge a complete linkage dominant marker maps. The key for doing so is to efficiently estimate recombination fractions between dominant markers in repulsion phases. RESULT: We proposed an expectation least square (ELS) algorithm and binomial analysis of three-point gametes (BAT) for estimating gamete frequencies from F2 dominant and codominant marker data, respectively. The results obtained from simulated and real genotype datasets showed that the ELS algorithm was able to accurately estimate frequencies of gametes and outperformed the EM algorithm in estimating recombination fractions between dominant loci and recovering true linkage maps of 6 dominant loci in coupling and unknown linkage phases. Our BAT method also had smaller variances in estimation of two-point recombination fractions than the EM algorithm. CONCLUSION: ELS is a powerful method for accurate estimation of gamete frequencies in dominant three-locus system in an F2 population and BAT is a computationally efficient and fast method for estimating frequencies of three-point codominant gametes. PMID- 28984188 TI - ScaPD: a database for human scaffold proteins. AB - BACKGROUND: Scaffold proteins play a critical role in an increasing number of biological signaling processes, including simple tethering mechanism, regulating selectivity in pathways, shaping cellular behaviors. While many databases document the signaling pathways, few databases are devoted to the scaffold proteins that medicate signal transduction. RESULTS: Here, we have developed a user-friendly database, ScaPD, to describe computationally predicted, experimentally validated scaffold proteins and associated signaling pathways. It currently contains 273 scaffold proteins and 1118 associated signaling pathways. The database allows users to search, navigate and download the scaffold protein mediated signaling networks. CONCLUSIONS: Manually curated and predicted scaffold protein data will be a foundation for further investigation of the scaffold protein in the signal transduction. With maintained up-to-date data, ScaPD ( http://bioinfo.wilmer.jhu.edu/ScaPD ) will be a valuable resource for understanding how individual signaling pathways are regulated. PMID- 28984189 TI - The International Conference on Intelligent Biology and Medicine (ICIBM) 2016: from big data to big analytical tools. AB - The 2016 International Conference on Intelligent Biology and Medicine (ICIBM 2016) was held on December 8-10, 2016 in Houston, Texas, USA. ICIBM included eight scientific sessions, four tutorials, one poster session, four highlighted talks and four keynotes that covered topics on 3D genomics structural analysis, next generation sequencing (NGS) analysis, computational drug discovery, medical informatics, cancer genomics, and systems biology. Here, we present a summary of the nine research articles selected from ICIBM 2016 program for publishing in BMC Bioinformatics. PMID- 28984190 TI - Unsupervised deep learning reveals prognostically relevant subtypes of glioblastoma. AB - BACKGROUND: One approach to improving the personalized treatment of cancer is to understand the cellular signaling transduction pathways that cause cancer at the level of the individual patient. In this study, we used unsupervised deep learning to learn the hierarchical structure within cancer gene expression data. Deep learning is a group of machine learning algorithms that use multiple layers of hidden units to capture hierarchically related, alternative representations of the input data. We hypothesize that this hierarchical structure learned by deep learning will be related to the cellular signaling system. RESULTS: Robust deep learning model selection identified a network architecture that is biologically plausible. Our model selection results indicated that the 1st hidden layer of our deep learning model should contain about 1300 hidden units to most effectively capture the covariance structure of the input data. This agrees with the estimated number of human transcription factors, which is approximately 1400. This result lends support to our hypothesis that the 1st hidden layer of a deep learning model trained on gene expression data may represent signals related to transcription factor activation. Using the 3rd hidden layer representation of each tumor as learned by our unsupervised deep learning model, we performed consensus clustering on all tumor samples-leading to the discovery of clusters of glioblastoma multiforme with differential survival. One of these clusters contained all of the glioblastoma samples with G-CIMP, a known methylation phenotype driven by the IDH1 mutation and associated with favorable prognosis, suggesting that the hidden units in the 3rd hidden layer representations captured a methylation signal without explicitly using methylation data as input. We also found differentially expressed genes and well-known mutations (NF1, IDH1, EGFR) that were uniquely correlated with each of these clusters. Exploring these unique genes and mutations will allow us to further investigate the disease mechanisms underlying each of these clusters. CONCLUSIONS: In summary, we show that a deep learning model can be trained to represent biologically and clinically meaningful abstractions of cancer gene expression data. Understanding what additional relationships these hidden layer abstractions have with the cancer cellular signaling system could have a significant impact on the understanding and treatment of cancer. PMID- 28984191 TI - Robust mutant strain design by pessimistic optimization. AB - BACKGROUND: Flux Balance Analysis (FBA) based mathematical modeling enables in silico prediction of systems behavior for genome-scale metabolic networks. Computational methods have been derived in the FBA framework to solve bi-level optimization for deriving "optimal" mutant microbial strains with targeted biochemical overproduction. The common inherent assumption of these methods is that the surviving mutants will always cooperate with the engineering objective by overproducing the maximum desired biochemicals. However, it has been shown that this optimistic assumption may not be valid in practice. METHODS: We study the validity and robustness of existing bi-level methods for strain optimization under uncertainty and non-cooperative environment. More importantly, we propose new pessimistic optimization formulations: P-ROOM and P-OptKnock, aiming to derive robust mutants with the desired overproduction under two different mutant cell survival models: (1) ROOM assuming mutants have the minimum changes in reaction fluxes from wild-type flux values, and (2) the one considered by OptKnock maximizing the biomass production yield. When optimizing for desired overproduction, our pessimistic formulations derive more robust mutant strains by considering the uncertainty of the cell survival models at the inner level and the cooperation between the outer- and inner-level decision makers. For both P ROOM and P-OptKnock, by converting multi-level formulations into single-level Mixed Integer Programming (MIP) problems based on the strong duality theorem, we can derive exact optimal solutions that are highly scalable with large networks. RESULTS: Our robust formulations P-ROOM and P-OptKnock are tested with a small E. coli core metabolic network and a large-scale E. coli iAF1260 network. We demonstrate that the original bi-level formulations (ROOM and OptKnock) derive mutants that may not achieve the predicted overproduction under uncertainty and non-cooperative environment. The knockouts obtained by the proposed pessimistic formulations yield higher chemical production rates than those by the optimistic formulations. Moreover, with higher uncertainty levels, both cellular models under pessimistic approaches produce the same mutant strains. CONCLUSIONS: In this paper, we propose a new pessimistic optimization framework for mutant strain design. Our pessimistic strain optimization methods produce more robust solutions regardless of the inner-level mutant survival models, which is desired as the models for cell survival are often approximate to real-world systems. Such robust and reliable knockout strategies obtained by the pessimistic formulations would provide confidence for in-vivo experimental design of microbial mutants of interest. PMID- 28984192 TI - A link prediction approach to cancer drug sensitivity prediction. AB - BACKGROUND: Predicting the response to a drug for cancer disease patients based on genomic information is an important problem in modern clinical oncology. This problem occurs in part because many available drug sensitivity prediction algorithms do not consider better quality cancer cell lines and the adoption of new feature representations; both lead to the accurate prediction of drug responses. By predicting accurate drug responses to cancer, oncologists gain a more complete understanding of the effective treatments for each patient, which is a core goal in precision medicine. RESULTS: In this paper, we model cancer drug sensitivity as a link prediction, which is shown to be an effective technique. We evaluate our proposed link prediction algorithms and compare them with an existing drug sensitivity prediction approach based on clinical trial data. The experimental results based on the clinical trial data show the stability of our link prediction algorithms, which yield the highest area under the ROC curve (AUC) and are statistically significant. CONCLUSIONS: We propose a link prediction approach to obtain new feature representation. Compared with an existing approach, the results show that incorporating the new feature representation to the link prediction algorithms has significantly improved the performance. PMID- 28984193 TI - DRREP: deep ridge regressed epitope predictor. AB - INTRODUCTION: The ability to predict epitopes plays an enormous role in vaccine development in terms of our ability to zero in on where to do a more thorough in vivo analysis of the protein in question. Though for the past decade there have been numerous advancements and improvements in epitope prediction, on average the best benchmark prediction accuracies are still only around 60%. New machine learning algorithms have arisen within the domain of deep learning, text mining, and convolutional networks. This paper presents a novel analytically trained and string kernel using deep neural network, which is tailored for continuous epitope prediction, called: Deep Ridge Regressed Epitope Predictor (DRREP). RESULTS: DRREP was tested on long protein sequences from the following datasets: SARS, Pellequer, HIV, AntiJen, and SEQ194. DRREP was compared to numerous state of the art epitope predictors, including the most recently published predictors called LBtope and DMNLBE. Using area under ROC curve (AUC), DRREP achieved a performance improvement over the best performing predictors on SARS (13.7%), HIV (8.9%), Pellequer (1.5%), and SEQ194 (3.1%), with its performance being matched only on the AntiJen dataset, by the LBtope predictor, where both DRREP and LBtope achieved an AUC of 0.702. CONCLUSION: DRREP is an analytically trained deep neural network, thus capable of learning in a single step through regression. By combining the features of deep learning, string kernels, and convolutional networks, the system is able to perform residue-by-residue prediction of continues epitopes with higher accuracy than the current state of the art predictors. PMID- 28984194 TI - The International Conference on Intelligent Biology and Medicine (ICIBM) 2016: putting systems biology to work. AB - Between December 8-10, 2016, the International Conference on Intelligent Biology and Medicine (ICIBM 2016) was held in Houston, Texas, USA. The conference included eight scientific sessions, four tutorials, one poster session, four highlighted talks and four keynotes that covered topics in 3D genome structure analysis and visualization, next generation sequencing analysis, computational drug discovery, medical informatics, cancer genomics and systems biology. Systems biology has been a main theme in ICIBM 2016, with exciting advances were presented in many areas of systems biology. Here, we selected seven high quality papers to be published in BMC Systems Biology. PMID- 28984195 TI - MD-Miner: a network-based approach for personalized drug repositioning. AB - BACKGROUND: Due to advances in next generation sequencing technologies and corresponding reductions in cost, it is now attainable to investigate genome-wide gene expression and variants at a patient-level, so as to better understand and anticipate heterogeneous responses to therapy. Consequently, it is feasible to inform personalized drug treatment decisions using personal genomics data. However, these efforts are limited due to a lack of reliable computational approaches for predicting effective drugs for individual patients. The reverse gene set enrichment analysis (i.e., connectivity mapping) approach and its variants have been widely and successfully used for drug prediction. However, the performance of these methods is limited by undefined mechanism of action (MoA) of drugs and reliance on cohorts of patients rather than personalized predictions for individual patients. RESULTS: In this study, we have developed and evaluated a computational approach, known as Mechanism and Drug Miner (MD-Miner), using a network-based computational approach to predict effective drugs and reveal potential drug mechanisms of action at the level of signaling pathways. Specifically, the patient-specific signaling network is constructed by integrating known disease associated genes with patient-derived gene expression profiles. In parallel, a drug mechanism of action network is constructed by integrating drug targets and z-score profiles of drug-induced gene expression (pre vs. post-drug treatment). Potentially effective candidate drugs are prioritized according to the number of common genes between the patient-specific dysfunctional signaling network and drug MoA network. We evaluated the MD-Miner method on the PC-3 prostate cancer cell line, and showed that it significantly improved the success rate of discovering effective drugs compared with the random selection, and could provide insight into potential mechanisms of action. CONCLUSIONS: This work provides a signaling network-based drug repositioning approach. Compared with the reverse gene signature based drug repositioning approaches, the proposed method can provide clues of mechanism of action in terms of signaling transduction networks. PMID- 28984196 TI - Multitype Bellman-Harris branching model provides biological predictors of early stages of adult hippocampal neurogenesis. AB - BACKGROUND: Adult hippocampal neurogenesis, the process of formation of new neurons, occurs throughout life in the hippocampus. New neurons have been associated with learning and memory as well as mood control, and impaired neurogenesis has been linked to depression, schizophrenia, autism and cognitive decline during aging. Thus, understanding the biological properties of adult neurogenesis has important implications for human health. Computational models of neurogenesis have attempted to derive biologically relevant knowledge, hard to achieve using experimentation. However, the majority of the computational studies have predominantly focused on the late stages of neurogenesis, when newborn neurons integrate into hippocampal circuitry. Little is known about the early stages that regulate proliferation, differentiation, and survival of neural stem cells and their immediate progeny. RESULTS: Here, based on the branching process theory and biological evidence, we developed a computational model that represents the early stage hippocampal neurogenic cascade and allows prediction of the overall efficiency of neurogenesis in both normal and diseased conditions. Using this stochastic model with a simulation program, we derived the equilibrium distribution of cell population and simulated the progression of the neurogenic cascade. Using BrdU pulse-and-chase experiment to label proliferating cells and their progeny in vivo, we quantified labeled newborn cells and fit the model on the experimental data. Our simulation results reveal unknown but meaningful biological parameters, among which the most critical ones are apoptotic rates at different stages of the neurogenic cascade: apoptotic rates reach maximum at the stage of neuroblasts; the probability of neuroprogenitor cell renewal is low; the neuroblast stage has the highest temporal variance within the cell types of the neurogenic cascade, while the apoptotic stage is short. CONCLUSION: At a practical level, the stochastic model and simulation framework we developed will enable us to predict overall efficiency of hippocampal neurogenesis in both normal and diseased conditions. It can also generate predictions of the behavior of the neurogenic system under perturbations such as increase or decrease of apoptosis due to disease or treatment. PMID- 28984197 TI - Circular RNA expression profiles and features in human tissues: a study using RNA seq data. AB - BACKGROUND: Circular RNA (circRNA) is one type of noncoding RNA that forms a covalently closed continuous loop. Similar to long noncoding RNA (lncRNA), circRNA can act as microRNA (miRNA) 'sponges' to regulate gene expression, and its abnormal expression is related to diseases such as atherosclerosis, nervous system disorders and cancer. So far, there have been no systematic studies on circRNA abundance and expression profiles in human adult and fetal tissues. RESULTS: We explored circRNA expression profiles using RNA-seq data for six adult and fetal normal tissues (colon, heart, kidney, liver, lung, and stomach) and four gland normal tissues (adrenal gland, mammary gland, pancreas, and thyroid gland). A total of 8120, 25,933 and 14,433 circRNAs were detected by at least two supporting junction reads in adult, fetal and gland tissues, respectively. Among them, 3092, 14,241 and 6879 circRNAs were novel when compared to the published results. In each adult tissue type, we found at least 1000 circRNAs, among which 36.97-50.04% were tissue-specific. We reported 33 circRNAs that were ubiquitously expressed in all the adult tissues we examined. To further explore the potential "housekeeping" function of these circRNAs, we constructed a circRNA-miRNA-mRNA regulatory network containing 17 circRNAs, 22 miRNAs and 90 mRNAs. Furthermore, we found that both the abundance and the relative expression level of circRNAs were higher in fetal tissue than adult tissue. The number of circRNAs in gland tissues, especially in mammary gland (9665 circRNA candidates), was higher than that of other adult tissues (1160-3777). CONCLUSIONS: We systematically investigated circRNA expression in a variety of human adult and fetal tissues. Our observation of different expression level of circRNAs in adult and fetal tissues suggested that circRNAs might play their role in a tissue-specific and development-specific fashion. Analysis of circRNA-miRNA-mRNA network provided potential targets of circRNAs. High expression level of circRNAs in mammary gland might be attributed to the rich innervation. PMID- 28984198 TI - Genomic diversity and phylogeography of norovirus in China. AB - BACKGROUND: Little is known about the phylogeography of norovirus (NoV) in China. In norovirus, a clear understanding for the characteristics of tree topology, migration patterns and its demographic dynamics in viral circulation are needed to identify its prevalence trends, which can help us better prepare for its epidemics as well as develop useful control strategies. The aim of this study was to explore the genetic diversity, temporal distribution, demographic dynamics and migration patterns of NoV that circulated in China. RESULTS: Our analysis showed that two major genogroups, GI and GII, were identified in China, in which GII.3, GII.4 and GII.17 accounted for the majority with a total proportion around 70%. Our demography inference suggested that during the long-term migration process, NoV evolved into multiple lineages and then experienced a selective sweep, which reduced its genetic diversity. The phylogeography results suggested that the norovirus may have originated form the South China (Hong Kong and Guangdong), followed by multicenter direction outbreaks across the country. CONCLUSIONS: From these analyses, we indicate that domestic poultry trade and frequent communications of people from different regions have all contributed to the spread of the NoV in China. Together with recent advances in phylogeographic inference, our researches also provide powerful illustrations of how coalescent based methods can extract adequate information in molecular epidemiology. PMID- 28984199 TI - Roles of alternative splicing in modulating transcriptional regulation. AB - BACKGROUND: The ability of a transcription factor to regulate its targets is modulated by a variety of genetic and epigenetic mechanisms. Alternative splicing can modulate gene function by adding or removing certain protein domains, and therefore affect the activity of protein. Reverse engineering of gene regulatory networks using gene expression profiles has proven valuable in dissecting the logical relationships among multiple proteins during the transcriptional regulation. However, it is unclear whether alternative splicing of certain proteins affects the activity of other transcription factors. RESULTS: In order to investigate the roles of alternative splicing during transcriptional regulation, we constructed a statistical model to infer whether the alternative splicing events of modulator proteins can affect the ability of key transcription factors in regulating the expression levels of their transcriptional targets. We tested our strategy in KIRC (Kidney Renal Clear Cell Carcinoma) using the RNA-seq data downloaded from TCGA (the Cancer Genomic Atlas). We identified 828of modulation relationships between the splicing levels of modulator proteins and activity levels of transcription factors. For instance, we found that the activity levels of GR (glucocorticoid receptor) protein, a key transcription factor in kidney, can be influenced by the splicing status of multiple proteins, including TP53, MDM2 (mouse double minute 2 homolog), RBM14 (RNA-binding protein 14) and SLK (STE20 like kinase). The influenced GR-targets are enriched by key cancer-related pathways, including p53 signaling pathway, TR/RXR activation, CAR/RXR activation, G1/S checkpoint regulation pathway, and G2/M DNA damage checkpoint regulation pathway. CONCLUSIONS: Our analysis suggests, for the first time, that exon inclusion levels of certain regulatory proteins can affect the activities of many transcription factors. Such analysis can potentially unravel a novel mechanism of how splicing variation influences the cellular function and provide important insights for how dysregulation of splicing outcome can lead to various diseases. PMID- 28984200 TI - Incorporating genomic, transcriptomic and clinical data: a prognostic and stem cell-like MYC and PRC imbalance in high-risk neuroblastoma. AB - BACKGROUND: Previous studies suggested that cancer cells possess traits reminiscent of the biological mechanisms ascribed to normal embryonic stem cells (ESCs) regulated by MYC and Polycomb repressive complex 2 (PRC2). Several poorly differentiated adult tumors showed preferentially high expression levels in targets of MYC, coincident with low expression levels in targets of PRC2. This paper will reveal this ESC-like cancer signature in high-risk neuroblastoma (HR NB), the most common extracranial solid tumor in children. METHODS: We systematically assembled genomic variants, gene expression changes, priori knowledge of gene functions, and clinical outcomes to identify prognostic multigene signatures. First, we assigned a new, individualized prognostic index using the relative expressions between the poor- and good-outcome signature genes. We then characterized HR-NB aggressiveness beyond these prognostic multigene signatures through the imbalanced effects of MYC and PRC2 signaling. We further analyzed Retinoic acid (RA)-induced HR-NB cells to model tumor cell differentiation. Finally, we performed in vitro validation on ZFHX3, a cell differentiation marker silenced by PRC2, and compared cell morphology changes before and after blocking PRC2 in HR-NB cells. RESULTS: A significant concurrence existed between exons with verified variants and genes showing MYCN-dependent expression in HR-NB. From these biomarker candidates, we identified two novel prognostic gene-set pairs with multi-scale oncogenic defects. Intriguingly, MYC targets over-represented an unfavorable component of the identified prognostic signatures while PRC2 targets over-represented a favorable component. The cell cycle arrest and neuronal differentiation marker ZFHX3 was identified as one of PRC2-silenced tumor suppressor candidates. Blocking PRC2 reduced tumor cell growth and increased the mRNA expression levels of ZFHX3 in an early treatment stage. This hypothesis-driven systems bioinformatics work offered novel insights into the PRC2-mediated tumor cell growth and differentiation in neuroblastoma, which may exert oncogenic effects together with MYC regulation. CONCLUSION: Our results propose a prognostic effect of imbalanced MYC and PRC2 moderations in pediatric HR-NB for the first time. This study demonstrates an incorporation of genomic landscapes and transcriptomic profiles into the hypothesis-driven precision prognosis and biomarker discovery. The application of this approach to neuroblastoma, as well as other cancer more broadly, could contribute to reduced relapse and mortality rates in the long term. PMID- 28984201 TI - Identification of common oncogenic and early developmental pathways in the ovarian carcinomas controlling by distinct prognostically significant microRNA subsets. AB - BACKGROUND: High-grade serous ovarian carcinoma (HG-SOC) is the dominant tumor histologic type in epithelial ovarian cancers, exhibiting highly aberrant microRNA expression profiles and diverse pathways that collectively determine the disease aggressiveness and clinical outcomes. However, the functional relationships between microRNAs, the common pathways controlled by the microRNAs and their prognostic and therapeutic significance remain poorly understood. METHODS: We investigated the gene expression patterns of microRNAs in the tumors of 582 HG-SOC patients to identify prognosis signatures and pathways controlled by tumor miRNAs. We developed a variable selection and prognostic method, which performs a robust selection of small-sized subsets of the predictive features (e.g., expressed microRNAs) that collectively serves as the biomarkers of cancer risk and progression stratification system, interconnecting these features with common cancer-related pathways. RESULTS: Across different cohorts, our meta analysis revealed two robust and unbiased miRNA-based prognostic classifiers. Each classifier reproducibly discriminates HG-SOC patients into high-confidence low-, intermediate- or high-prognostic risk subgroups with essentially different 5-year overall survival rates of 51.6-85%, 20-38.1%, and 0-10%, respectively. Significant correlations of the risk subgroup's stratification with chemotherapy treatment response were observed. We predicted specific target genes involved in nine cancer-related and two oocyte maturation pathways (neurotrophin and progesterone-mediated oocyte maturation), where each gene can be controlled by more than one miRNA species of the distinct miRNA HG-SOC prognostic classifiers. CONCLUSIONS: We identified robust and reproducible miRNA-based prognostic subsets of the of HG-SOC classifiers. The miRNAs of these classifiers could control nine oncogenic and two developmental pathways, highlighting common underlying pathologic mechanisms and perspective targets for the further development of a personalized prognosis assay(s) and the development of miRNA-interconnected pathway-centric and multi-agent therapeutic intervention. PMID- 28984202 TI - SVachra: a tool to identify genomic structural variation in mate pair sequencing data containing inward and outward facing reads. AB - BACKGROUND: Characterization of genomic structural variation (SV) is essential to expanding the research and clinical applications of genome sequencing. Reliance upon short DNA fragment paired end sequencing has yielded a wealth of single nucleotide variants and internal sequencing read insertions-deletions, at the cost of limited SV detection. Multi-kilobase DNA fragment mate pair sequencing has supplemented the void in SV detection, but introduced new analytic challenges requiring SV detection tools specifically designed for mate pair sequencing data. Here, we introduce SVachra - Structural Variation Assessment of CHRomosomal Aberrations, a breakpoint calling program that identifies large insertions deletions, inversions, inter- and intra-chromosomal translocations utilizing both inward and outward facing read types generated by mate pair sequencing. RESULTS: We demonstrate SVachra's utility by executing the program on large-insert (Illumina Nextera) mate pair sequencing data from the personal genome of a single subject (HS1011). An additional data set of long-read (Pacific BioSciences RSII) was also generated to validate SV calls from SVachra and other comparison SV calling programs. SVachra exhibited the highest validation rate and reported the widest distribution of SV types and size ranges when compared to other SV callers. CONCLUSIONS: SVachra is a highly specific breakpoint calling program that exhibits a more unbiased SV detection methodology than other callers. PMID- 28984203 TI - System modeling reveals the molecular mechanisms of HSC cell cycle alteration mediated by Maff and Egr3 under leukemia. AB - BACKGROUND: Molecular mechanisms of the functional alteration of hematopoietic stem cells (HSCs) in leukemic environment attract intensive research interests. As known in previous researches, Maff and Egr3 are two important genes having opposite functions on cell cycle; however, they are both highly expressed in HSCs under leukemia. Hence, exploring the molecular mechanisms of how the genes act on cell cycle will help revealing the functional alteration of HSCs. RESULTS: We herein utilize the bioinformatic resources to computationally model the acting mechanisms of Maff and Egr3 on cell cycle. Using the data of functional experiments as reference, molecular acting mechanisms are optimally enumerated through model selection. The results are consolidated by evidences from gene sequence analysis, thus having enhanced the confidence of our pilot findings, which suggest that HSCs possibly undergo a "adaptation - suppression" process in response to the malignant environment of leukemia. CONCLUSION: As a pilot research, our results may provide valuable insights for further experimental studies. Meanwhile, our research method combining computational modeling and data from functional experiments can be worthwhile for knowledge discovery; and it can be generalized and extended to other biological/biomedical studies. PMID- 28984204 TI - SAIC: an iterative clustering approach for analysis of single cell RNA-seq data. AB - BACKGROUND: Research interests toward single cell analysis have greatly increased in basic, translational and clinical research areas recently, as advances in whole-transcriptome amplification technique allow scientists to get accurate sequencing result at single cell level. An important step in the single-cell transcriptome analysis is to identify distinct cell groups that have different gene expression patterns. Currently there are limited bioinformatics approaches available for single-cell RNA-seq analysis. Many studies rely on principal component analysis (PCA) with arbitrary parameters to identify the genes that will be used to cluster the single cells. RESULTS: We have developed a novel algorithm, called SAIC (Single cell Analysis via Iterative Clustering), that identifies the optimal set of signature genes to separate single cells into distinct groups. Our method utilizes an iterative clustering approach to perform an exhaustive search for the best parameters within the search space, which is defined by a number of initial centers and P values. The end point is identification of a signature gene set that gives the best separation of the cell clusters. Using a simulated data set, we showed that SAIC can successfully identify the pre-defined signature gene sets that can correctly separated the cells into predefined clusters. We applied SAIC to two published single cell RNA seq datasets. For both datasets, SAIC was able to identify a subset of signature genes that can cluster the single cells into groups that are consistent with the published results. The signature genes identified by SAIC resulted in better clusters of cells based on DB index score, and many genes also showed tissue specific expression. CONCLUSIONS: In summary, we have developed an efficient algorithm to identify the optimal subset of genes that separate single cells into distinct clusters based on their expression patterns. We have shown that it performs better than PCA method using published single cell RNA-seq datasets. PMID- 28984205 TI - The discrepancy among single nucleotide variants detected by DNA and RNA high throughput sequencing data. AB - BACKGROUND: High throughput sequencing technology enables the both the human genome and transcriptome to be screened at the single nucleotide resolution. Tools have been developed to infer single nucleotide variants (SNVs) from both DNA and RNA sequencing data. To evaluate how much difference can be expected between DNA and RNA sequencing data, and among tissue sources, we designed a study to examine the single nucleotide difference among five sources of high throughput sequencing data generated from the same individual, including exome sequencing from blood, tumor and adjacent normal tissue, and RNAseq from tumor and adjacent normal tissue. RESULTS: Through careful quality control and analysis of the SNVs, we found little difference between DNA-DNA pairs (1%-2%). However, between DNA-RNA pairs, SNV differences ranged anywhere from 10% to 20%. CONCLUSIONS: Only a small portion of these differences can be explained by RNA editing. Instead, the majority of the DNA-RNA differences should be attributed to technical errors from sequencing and post-processing of RNAseq data. Our analysis results suggest that SNV detection using RNAseq is subject to high false positive rates. PMID- 28984206 TI - Logo2PWM: a tool to convert sequence logo to position weight matrix. AB - BACKGROUND: position weight matrix (PWM) and sequence logo are the most widely used representations of transcription factor binding site (TFBS) in biological sequences. Sequence logo - a graphical representation of PWM, has been widely used in scientific publications and reports, due to its easiness of human perception, rich information, and simple format. Different from sequence logo, PWM works great as a precise and compact digitalized form, which can be easily used by a variety of motif analysis software. There are a few available tools to generate sequence logos from PWM; however, no tool does the reverse. Such tool to convert sequence logo back to PWM is needed to scan a TFBS represented in logo format in a publication where the PWM is not provided or hard to be acquired. A major difficulty in developing such tool to convert sequence logo to PWM is to deal with the diversity of sequence logo images. RESULTS: We propose logo2PWM for reconstructing PWM from a large variety of sequence logo images. Evaluation results on over one thousand logos from three sources of different logo format show that the correlation between the reconstructed PWMs and the original PWMs are constantly high, where median correlation is greater than 0.97. CONCLUSION: Because of the high recognition accuracy, the easiness of usage, and, the availability of both web-based service and stand-alone application, we believe that logo2PWM can readily benefit the study of transcription by filling the gap between sequence logo and PWM. PMID- 28984207 TI - The International Conference on Intelligent Biology and Medicine (ICIBM) 2016: summary and innovation in genomics. AB - In this editorial, we first summarize the 2016 International Conference on Intelligent Biology and Medicine (ICIBM 2016) that was held on December 8-10, 2016 in Houston, Texas, USA, and then briefly introduce the ten research articles included in this supplement issue. ICIBM 2016 included four workshops or tutorials, four keynote lectures, four conference invited talks, eight concurrent scientific sessions and a poster session for 53 accepted abstracts, covering current topics in bioinformatics, systems biology, intelligent computing, and biomedical informatics. Through our call for papers, a total of 77 original manuscripts were submitted to ICIBM 2016. After peer review, 11 articles were selected in this special issue, covering topics such as single cell RNA-seq analysis method, genome sequence and variation analysis, bioinformatics method for vaccine development, and cancer genomics. PMID- 28984208 TI - Unique protein expression signatures of survival time in kidney renal clear cell carcinoma through a pan-cancer screening. AB - BACKGROUND: In 2016, it is estimated that there will be 62,700 new cases of kidney cancer in the United States, and 14,240 patients will die from the disease. Because the incidence of kidney renal clear cell carcinoma (KIRC), the most common type of kidney cancer, is expected to continue to increase in the US, there is an urgent need to find effective diagnostic biomarkers for KIRC that could help earlier detection of and customized treatment strategies for the disease. Accordingly, in this study we systematically investigated KIRC's prognostic biomarkers for survival using the reverse phase protein array (RPPA) data and the high throughput sequencing data from The Cancer Genome Atlas (TCGA). RESULTS: With comprehensive data available in TCGA, we systematically screened protein expression based survival biomarkers in 10 major cancer types, among which KIRC presented many protein prognostic biomarkers of survival time. This is in agreement with a previous report that expression level changes (mRNAs, microRNA and protein) may have a better performance for prognosis of KIRC. In this study, we also identified 52 prognostic genes for KIRC, many of which are involved in cell-cycle and cancer signaling, as well as 15 tumor-stage-specific prognostic biomarkers. Notably, we found fewer prognostic biomarkers for early stage than for late-stage KIRC. Four biomarkers (the RPPA protein IDs: FASN, ACC1, Cyclin_B1 and Rad51) were found to be prognostic for survival based on both protein and mRNA expression data. CONCLUSIONS: Through pan-cancer screening, we found that many protein biomarkers were prognostic for patients' survival in KIRC. Stage-specific survival biomarkers in KIRC were also identified. Our study indicated that these protein biomarkers might have potential clinical value in terms of predicting survival in KIRC patients and developing individualized treatment strategies. Importantly, we found many biomarkers in KIRC at both the mRNA expression level and the protein expression level. These biomarkers shared a significant overlap, indicating that they were technically replicable. PMID- 28984209 TI - Genome-wide identification of key modulators of gene-gene interaction networks in breast cancer. AB - BACKGROUND: With the advances in high-throughput gene profiling technologies, a large volume of gene interaction maps has been constructed. A higher-level layer of gene-gene interaction, namely modulate gene interaction, is composed of gene pairs of which interaction strengths are modulated by (i.e., dependent on) the expression level of a key modulator gene. Systematic investigations into the modulation by estrogen receptor (ER), the best-known modulator gene, have revealed the functional and prognostic significance in breast cancer. However, a genome-wide identification of key modulator genes that may further unveil the landscape of modulated gene interaction is still lacking. RESULTS: We proposed a systematic workflow to screen for key modulators based on genome-wide gene expression profiles. We designed four modularity parameters to measure the ability of a putative modulator to perturb gene interaction networks. Applying the method to a dataset of 286 breast tumors, we comprehensively characterized the modularity parameters and identified a total of 973 key modulator genes. The modularity of these modulators was verified in three independent breast cancer datasets. ESR1, the encoding gene of ER, appeared in the list, and abundant novel modulators were illuminated. For instance, a prognostic predictor of breast cancer, SFRP1, was found the second modulator. Functional annotation analysis of the 973 modulators revealed involvements in ER-related cellular processes as well as immune- and tumor-associated functions. CONCLUSIONS: Here we present, as far as we know, the first comprehensive analysis of key modulator genes on a genome wide scale. The validity of filtering parameters as well as the conservativity of modulators among cohorts were corroborated. Our data bring new insights into the modulated layer of gene-gene interaction and provide candidates for further biological investigations. PMID- 28984210 TI - A systematic analysis of FDA-approved anticancer drugs. AB - BACKGROUND: The discovery of novel anticancer drugs is critical for the pharmaceutical research and development, and patient treatment. Repurposing existing drugs that may have unanticipated effects as potential candidates is one way to meet this important goal. Systematic investigation of efficient anticancer drugs could provide valuable insights into trends in the discovery of anticancer drugs, which may contribute to the systematic discovery of new anticancer drugs. RESULTS: In this study, we collected and analyzed 150 anticancer drugs approved by the US Food and Drug Administration (FDA). Based on drug mechanism of action, these agents are divided into two groups: 61 cytotoxic-based drugs and 89 target based drugs. We found that in the recent years, the proportion of targeted agents tended to be increasing, and the targeted drugs tended to be delivered as signal drugs. For 89 target-based drugs, we collected 102 effect-mediating drug targets in the human genome and found that most targets located on the plasma membrane and most of them belonged to the enzyme, especially tyrosine kinase. From above 150 drugs, we built a drug-cancer network, which contained 183 nodes (150 drugs and 33 cancer types) and 248 drug-cancer associations. The network indicated that the cytotoxic drugs tended to be used to treat more cancer types than targeted drugs. From 89 targeted drugs, we built a cancer-drug-target network, which contained 214 nodes (23 cancer types, 89 drugs, and 102 targets) and 313 edges (118 drug-cancer associations and 195 drug-target associations). Starting from the network, we discovered 133 novel drug-cancer associations among 52 drugs and 16 cancer types by applying the common target-based approach. Most novel drug cancer associations (116, 87%) are supported by at least one clinical trial study. CONCLUSIONS: In this study, we provided a comprehensive data source, including anticancer drugs and their targets and performed a detailed analysis in term of historical tendency and networks. Its application to identify novel drug cancer associations demonstrated that the data collected in this study is promising to serve as a fundamental for anticancer drug repurposing and development. PMID- 28984211 TI - [Multidisciplinary treatment of chronic pancreatitis: an overview of current step up approach and new options]. AB - - Chronic pancreatitis is a progressive inflammatory disease, which leads to a severe decrease in quality of life and reduced life expectancy.- 85-90% of patients with chronic pancreatitis consult the doctor because of pain.- Pain in chronic pancreatitis has a multifactorial aetiology, with nociceptive and neuropathological components.- Current treatment of chronic pancreatitis uses a step-up approach, starting with lifestyle interventions and medication, followed by endoscopic or surgical treatment or a combination of these two.- Surgical drainage or resection is more effective than repeated endoscopic treatment for patients with advanced chronic pancreatitis who use opiates.- There are indications that early surgical intervention in painful chronic pancreatitis and a dilated pancreatic duct provides better results than the current step-up approach; this is currently being investigated in the ESCAPE trial. PMID- 28984212 TI - [Fatal intoxication with nicotine for e-cigarette]. AB - BACKGROUND: Since the introduction of the electronic e-cigarette a few years ago, its use has greatly increased. The liquid formulations used in these e-cigarettes contain nicotine in high concentrations; ingestion of these liquids can be fatal. CASE DESCRIPTION: A 42-year-old male was admitted to the Intensive Care ward due to cardiac arrest. The patient had ingested highly concentrated liquid nicotine, originating from a vial with liquid for e-cigarettes. When the ambulance personnel found the patient he did not have a pulse; following CPR and administration of adrenaline his pulse returned. Upon admission, the plasma nicotine level was high at 3.0 mg/l (reference values for a smoker are 0.01-0.05 mg/l) and the patient's neurological function was poor. The patient was treated symptomatically, but eventually died of a postanoxic encephalopathy. CONCLUSION: Nicotine e-liquids are highly concentrated. Intentional ingestion can lead to toxic levels of nicotine which are associated with cardiac arrhythmias or arrest. Because even a few millilitres can be lethal, nicotine intoxication due to e liquid ingestion should be considered potentially life-threatening. PMID- 28984213 TI - [Superglue instead of eye ointment; the sealed eye: often frightening and painful, generally ends well]. AB - BACKGROUND: Not infrequently, patients mistakenly put glue in their eye. This often induces considerable emotional and physical reaction. CASE DESCRIPTION: A 20-year-old man came to the Emergency Department at night because he had mistaken a tube of superglue for his eye ointment and instilled the glue into his right eye. All the glue was removed, as were most of his eyelashes. The glue-induced corneal abrasion healed completely and the patient did not sustain any permanent injury. CONCLUSION: Despite the considerable dismay and severe pain caused by mistakenly introducing superglue into the eye, most cases have a favourable outcome. PMID- 28984214 TI - [Tilting at WIP windmills in the OR: laminar flow might be harmful]. AB - The World Health Organization has published a new guideline for the prevention of surgical site infection (SSI), according to which laminar airflow systems should not be used to reduce the risk of SSI in the OR. The Dutch Health Care Inspectorate has, on the other hand, published a directive demanding laminar airflow in most operation rooms in Dutch hospitals. This directive is based on an evidence-based report from the Dutch Working Group on Infection Prevention (WIP). Since these guidelines are contradictory, the evidence presented in the WHO report as well as in the WIP report is evaluated in this article. The conclusion is that the WIP report used the available literature selectively, resulting in a favourable but false advantage for the laminar airflow system. The directive on laminar airflow should therefore be withdrawn and the WHO guideline should be implemented in Dutch hospitals. PMID- 28984215 TI - Roseomonas terricola sp. nov., isolated from agricultural soil. AB - A novel strain, designated EM302T, was isolated from a soil sample collected from farmland located in Yesan-gun in the Republic of Korea. The cells were Gram-stain negative, aerobic, non-motile without flagella and coccobacilli-shaped. Colonies were circular with entire edges, convex, opaque and pink. The strain grew at 15 40 C (optimum, 35 C) and pH 6.0-9.0 (optimum, 7.0). The strain grew in R2A medium without the addition of NaCl. Based on 16S rRNA gene sequences analysis, strain EM302T was found to be phylogenetically related to Roseomonas wooponensis WW53T (96.5 % 16S rRNA gene sequence similarity), Roseomonas arcticisoli MC 3624T (95.2 %), Roseomonas aerilata 5420-30T (94.5 %), Roseomonas pecuniae N75T (94.4 %) and Roseomonas vinacea CPCC 100056T (94.4 %). The major cellular fatty acids were summed feature 8 (C18 : 1omega7c and/or C18 : 1omega6c) and C16 : 0. The predominant respiratory quinone was Q-10. The major polar lipids were phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol and an unidentified aminolipid. The DNA G+C content of the type strain was 65.7 mol%. On the basis of data presented here, strain EM302T is considered to represent a novel species of the genus Roseomonas, for which the name Roseomonasterricola sp. nov. is proposed. The type strain is EM302T (=KACC 13942T=KCTC 42906T=NBRC 111477T). PMID- 28984216 TI - Streptomyces roietensis sp. nov., an endophytic actinobacterium isolated from the surface-sterilized stem of jasmine rice, Oryza sativa KDML 105. AB - An endophytic actinobacterium, strain WES2T, was isolated from the stem of a jasmine rice plant collected from a paddy field in Thung Gura Rong Hai, Roi Et province, Thailand. As a result of a polyphasic study, this strain was identified as representing a novel member of the genus Streptomyces. This strain was a Gram stain-positive, aerobic actinobacterium with well-developed substrate mycelia and forming chains of looped spores. The closest phylogenetic relations, which shared the highest 16S rRNA gene sequence similarity, were Streptomyces nogalater JCM 4799T and Streptomyces lavenduligriseus NRRL-ISP 5487T at 99.1 and 99.0 %, respectively. Chemotaxonomic data, including major fatty acids, cell wall components and major menaquinones, confirmed the affiliation of WES2T to the genus Streptomyces. The data from the phylogenetic analysis, including physiological and biochemical studies and DNA-DNA hybridization, revealed the genotypic and phenotypic differentiation of WES2T from the most closely related species with validly published names. The name proposed for the novel species is Streptomycesroietensis sp. nov. The type strain is WES2T (=DSM 101729=NRRL B 65344). PMID- 28984217 TI - Kordia zosterae sp. nov., isolated from the seaweed, Zostera marina. AB - A Gram-stain-negative, gliding and rod shaped bacterium, designated strain ZO2 23T was isolated from a seaweed sample collected from the West Sea, Republic of Korea. Cells are catalase-negative and oxidase-positive. Neighbour-joining phylogenetic tree based on 16S rRNA gene sequences showed that strain ZO2-23T forms an independent lineage within the genus Kordia. Strain ZO2-23T was related to Kordia ulvae SC2T (98.0 %, 16S rRNA gene sequence similarity) and K. antarctica IMCC3317T (97.9 %). The major fatty acids of strain ZO2-23T were iso C15 : 0, iso-C17 : 0 3-OH, summed feature 3 and iso-C15 : 0 3-OH. The only isoprenoid quinone of the isolate was menaquinone-6. The DNA G+C content of strain ZO2-23T was 31.7 mol%. Phenotypic characteristics distinguished strain ZO2 23T from the related species of the genus Kordia. On the basis of the evidences presented in this study, novel species, Kordia zosterae sp. nov., is proposed for strain ZO2-23T (=KCTC 52268T=JCM 31799T). PMID- 28984218 TI - Pedobacter solisilvae sp. nov., isolated from forest soil. AB - The bacteria strain EN12T was isolated from forest soil in the Republic of Korea. The cells were Gram-negative, non-motile and rod-shaped, and the strain was strictly aerobic. Phylogenetic analysis of its 16S rRNA gene sequences showed that strain EN12T belonged to the class Sphingobacteriia of the phylum Bacteroidetes, and its closest relative is Pedobacter namyangjuensis 5G38T, with a sequence similarity of 95.5 %. The average DNA sequence similarity from validly described species within the genus Pedobacter was 92.5+/-1.3 %. Chemotaxonomic data including major ubiquinones (menaquinone-7), polar lipids (phosphatidylethanolamine and sphingolipid) and fatty acids (iso-C15 : 0, iso-C17 : 0 3-OH, and C16 : 1omega6c/C16 : 1omega7c) also supported an affiliation of strain EN12T with the genus Pedobacter. Genotypic and phenotypic differentiation of strain EN12T from six published Pedobacter species was revealed through DNA DNA relatedness and physiological/biochemical tests. Results of these phenotypic, phylogenetic and chemotaxonomic analyses indicated that strain EN12T is a novel species in the genus Pedobacter, for which we propose the name Pedobacter solisilvae sp. nov. (=KCTC 42612T=LMG 28820T). PMID- 28984219 TI - Psychrosphaera aquimarina sp. nov., a marine bacterium isolated from seawater collected from Asan Bay, Republic of Korea. AB - Cells of strain SW33T, isolated from the seawater of Asan Bay, Republic of Korea, were characterized as Gram-stain-negative, aerobic, rod-shaped, motile and non spore-forming. Phylogenetic analysis revealed that strain SW33T belonged to the genus Psychrosphaera and clustered distantly with the other genera in the family Pseudoalteromonadaceae in the phylogenetic tree. The 16S rRNA sequences of strain SW33T revealed high similarities to Psychrosphaera saromensis SA4-48T (98.7 %), Psychrosphaera haliotis KDW4T (97.4 %) and Psychrosphaera aestuarii PSC101T (97.3 %). The major fatty acids were C16 : 0 (27.9 %), summed feature 3 (32.2 %) and summed feature 8 (17.2 %). The predominant quinone was Q-8, and the polar lipid profile consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol and an unidentified amino lipid. The DNA G+C content was 38.3 mol%. The DNA-DNA relatedness values with the three species of Psychrosphaera saromensis KCTC 23240T, Psychrosphaera haliotis KCTC 22500T and Psychrosphaera aestuarii KCTC 32274T were 22, 23 and 18 %, respectively. Based on the phenotypic characteristics and taxonomic analyses, we propose that strain SW33T represents a novel species within the genus Psychrosphaera, for which the name Psychrosphaera aquimarina sp. nov. with the type strain SW33T (=KCTC 52743T=CICC 24249T) is proposed. PMID- 28984220 TI - Hymenobacter gummosus sp. nov., isolated from a spring. AB - Strain ANT-18T, isolated from a water sample taken from the Longtoushan Spring in Taiwan, was characterized using a polyphasic taxonomic approach. Cells of strain ANT-18T were Gram-stain-negative, aerobic, motile by gliding rods that were surrounded by a thick capsule and it formed pink colonies. Growth occurred at 20 37 degrees C (optimum, 25 degrees C), at pH 6-8 (optimum, pH 7) and with 0-1 % NaCl (w/; optimum, 0 %). Phylogenetic analyses, based on 16S rRNA gene sequences, showed that strain ANT-18T belongs to the genus Hymenobacter and showed the highest levels of sequence similarity to Hymenobacter ocellatus Myx 2105T (97.8 %) and Hymenobacter paludis KBP-30T (97.7 %). Strain ANT-18T contained iso-C15 : 0, anteiso-C15 : 0, C18 : 0 and summed feature 4 (iso-C17 : 1 I and/or anteiso C17 : 1 B) as the predominant fatty acids. The major isoprenoid quinone was MK-7. The polar lipid profile consisted of phosphatidylethanolamine, one uncharacterized aminolipid, two uncharacterized aminophospholipids, two uncharacterized glycolipids and seven uncharacterized lipids. The major polyamine was homospermidine. The genomic DNA G+C content of strain ANT-18T was 63.6 mol%. The DNA-DNA relatedness values of strain ANT-18T with respect to H. ocellatus Myx 2105T and H. paludis KBP-30T were less than 35 %. On the basis of the phylogenetic inference and phenotypic data, strain ANT-18T is recognized to be a representative of a novel species within the genus Hymenobacter. The name Hymenobacter gummosus sp. nov. is proposed, with strain ANT-18T (=BCRC 80966T=LMG 29477T=KCTC 52166T) as the type strain. PMID- 28984221 TI - Hymenobacter cavernae sp. nov., isolated from a karst cave. AB - A novel Gram-stain-negative, rod-shaped, non-motile and red-pigmented bacterial strain, designated K1E01-27T, was isolated from an animal excrement sample which was found in a karst cave located in Guizhou province, China. The phylogenetic analysis based on 16S rRNA gene sequences indicated that strain K1E01-27T represented a member of the genus Hymenobacter within the family Cytophagaceae of the phylum Bacteroidetes. Strain K1E01-27T was most closely related to Hymenobacter algoricola VUG-A23aT, with 95.1 % 16S rRNA gene sequence similarity. Growth of strain K1E01-27T occurred at 4-35 degrees C, at pH 5-9 and in the presence of 0-0.5 % (w/v) NaCl. The major fatty acids were iso-C15 : 0, anteiso C15 : 0, C16 : 1omega5c, summed feature 3 (comprising C16 : 1omega6c and/or C16 : 1omega7c) and summed feature 4 (comprising iso-C17 : 1 I/anteiso-C17 : 1 B). The major isoprenoid quinone was menaquinone 7 (MK-7). The major polar lipids were phosphatidylethanolamine, five unidentified aminophospholipids, three unidentified glycolipids, two unidentified phospholipids and one unidentified polar lipid. The DNA G+C content of the genomic DNA was 54.9 mol%. On the basis of phylogenetic, phenotypic and chemotaxonomic characteristics, strain K1E01-27T is considered to represent a novel species of the genus Hymenobacter, for which the name Hymenobacter cavernae sp. nov. is proposed. The type strain is K1E01-27T (=CGMCC 1.15197T=NBRC 112610T). PMID- 28984222 TI - Ancylobacter sonchi sp. nov., a novel methylotrophic bacterium from roots of Sonchus arvensis L. AB - An aerobic facultatively methylotrophic bacterium was isolated from roots of Sonchus arvensis L. and designated strain OsotT The cells of this strain were Gram-stain-negative, asporogenous, motile short rods multiplying by binary fisson. They utilized methanol, methylamines and a variety of polycarbon compounds as the carbon and energy sources. Methanol was assimilated after sequential oxidation to formaldehyde and CO2 via the ribulose bisphosphate pathway. The organism grew optimally at 22-29 degrees C and pH 7.5-8.0. The dominant phospholipids were phosphatidylethanolamine, phosphatidylcholine, phosphatidylglycerol and diphosphatidylglycerol (cardiolipin). The major cellular fatty acids of strain OsotT cells grown in R2A medium were C18 : 1omega7c (49.0 %), C19 : 0omega8c cyclo (38.3 %) and C16 : 0 (8.4 %). The major ubiquinone was Q 10. The DNA G+C content of strain OsotT was 66.1 mol% (Tm). On the basis of 16S rRNA gene sequence analysis strain OsotT is phylogenetically related to the members of genus Ancylobacter (97.1-98.8 % sequence similarity). Based on 16S rRNA gene sequence analysis and DNA-DNA relatedness (27-29 %) with type strains of the genus Ancylobacter, the novel isolate is classified as a new species of this genus and named Ancylobacter sonchi sp. nov.; the type strain is OsotT (=VKM B-3145T=JCM 32039T). PMID- 28984223 TI - Sphingobacterium tabacisoli sp. nov., isolated from a tobacco field soil sample. AB - A Gram-staining-negative, non-motile and rod-shaped bacterium, designated strain h337T, was isolated from an arable soil sample of a tobacco field in Kunming, south-west China. The cells showed oxidase-positive and catalase-positive reactions. Growth was observed at 10-35 degrees C, at pH 6.0-9.0 and in the presence of up to 3 % (w/v) NaCl, with optimal growth at 30 degrees C, pH 7.0 and with 1-2 % (w/v) NaCl. The predominant isoprenoid quinone was MK-7. The major fatty acids were identified as iso-C15 : 0, iso-C17 : 0 3-OH, summed feature 3 (C16 : 1omega7c and/or C16 : 1omega6c) and summed feature 4 (iso-C17 : 1 I and/or anteiso-C17 : 1 B). The cellular polar lipids contained phosphatidylethanolamine, sphingophospholipid, four unidentified phospholipids, five unidentified lipids and three unidentified aminophospholipids. The genomic DNA G+C content was 41.5 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain h337T should be assigned to the genus Sphingobacterium. 16S rRNA gene sequence similarity analysis showed that strain h337T was most closely related to 'Sphingobacteriumyamdrokense' 3-0-1 (98.8 %) and Sphingobacteriumyanglingense CCNWSP36-1T (98.5 %) and shared less than 97 % similarity with other species of the genus Sphingobacterium. DNA-DNA hybridization data indicated that the isolate represented a novel genomic species belonging to the genus Sphingobacterium. The characteristics determined in this polyphasic taxonomic study indicated that strain h337T represents a novel species of the genus Sphingobacterium, for which the name Sphingobacterium tabacisoli sp. nov. (type strain h337T=KCTC 52298T=CCTCC AB 2017155T) is proposed. PMID- 28984224 TI - Phenylobacterium deserti sp. nov., isolated from desert soil. AB - A novel bacterial strain, designated YIM 73061T, was isolated from the Cholistan desert in Punjab, Pakistan, and characterized by using a polyphasic taxonomic approach. 16S rRNA gene sequence analysis revealed the highest levels of sequence similarity with respect to Phenylobacterium conjunctum FWC21T (97.6 %), Phenylobacterium lituiforme FaiI3T (97.4 %), Phenylobacteriumcomposti 4T-6T (97.0 %) and Phenylobacterium aquaticum W2-3-4T (96.8 %). Cells were Gram-stain negative, aerobic and motile rods that formed orange colonies. The strain was oxidase- and catalase-positive. Growth occurred at 20-40 degrees C (optimum, 30 37 degrees C) at pH 5.0-8.0 (optimum, pH 7.0) and with 0-1 % (w/v) NaCl (optimum, 0-0.5 %). The major cellular fatty acids (>10 %) were summed feature 8 (comprising C18 : 1omega7c and/or C18 : 1omega6c) and C16 : 0. The polar lipid profile consisted of phosphatidylglycerol and four unidentified glycolipids. The major isoprenoid quinone was ubiquinone-10 (Q-10). The G+C content of the genomic DNA was 66.8 mol%. Strain YIM 73061T showed low levels of DNA-DNA relatedness to P. conjunctum FWC21T (27.2+/-2.6 %), P. lituiforme FaiI3T (24.6+/-1.1 %) and P.composti 4T-6T (18.4+/-3.1 %). On the basis of phylogenetic inference, chemotaxonomic characteristics and phenotypic data, strain YIM 73061T should be classified as representing a novel species, for which the name Phenylobacterium deserti sp. nov. is proposed. The type strain is YIM 73061T (=DSM 103871T=CCTCC AB 2016297T). PMID- 28984225 TI - Sediminibacterium roseum sp. nov., isolated from sewage sediment. AB - A novel bacterial strain, designated SYL130T, was isolated from the sewage sediment of a park in Busan, Korea. The strain was aerobic, producing orange colonies on R2A agar. Cells were single, Gram-stain-negative rods and were motile by gliding. Phylogenetic analyses, based on 16S rRNA gene sequences, showed that strain SYL130T was most closely related to Sediminibacterium aquarii JCM 31013T (96.1 %). The major fatty acids (>5 % of the total) of strain SYL130T were iso C15 : 0 (28.3 %), iso-C15 : 1 G (23.2 %), iso-C17 : 0 3-OH (9.6 %), anteiso-C15 : 0 (5.9 %) and iso-C16 : 0 3-OH (5.6 %). The major polar lipids were phosphatidylethanolamine, one unidentified phospholipid, one unidentified aminolipid, two unidentified aminophospholipids and six unidentified polar lipids. The predominant respiratory quinone was MK-7. The DNA G+C content was 47.8 mol%. Strain SYL130T had clearly differential characteristics to related species including the temperature and pH ranges for growth, and being positive for l-arabinose and maltose, and negative for alpha-galactosidase activity. On the basis of phenotypic, chemotaxonomic and genotypic analyses, strain SYL130T represents a novel species of the genus Sediminibacterium, for which the name Sediminibacterium roseum sp. nov., is proposed. The type strain Sediminibacterium roseum is SYL130T (=KCTC 52860T=CCTCC AB 2017082T). PMID- 28984226 TI - Clotrimazole is highly effective in vitro against feline Sporothrix brasiliensis isolates. AB - PURPOSE: Sporothrix brasiliensis, the most virulent species in the Sporothrix schenckii complex, is responsible for the ongoing epidemics of human and animal sporotrichosis in Brazil. Feline outbreaks are usually driven by S. brasiliensis and followed by extensive transmission to humans. Itraconazole is the first-line treatment for both feline and human sporotrichosis; however, reduced sensitivity is an emerging issue. Thus, we investigated the effect of the widely used antifungal clotrimazole - alone or in combination with itraconazole - against the pathogenic (yeast) form of feline and human S. brasiliensis isolates, in vitro. METHODOLOGY: Minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values were determined for treatment with clotrimazole and itraconazole, as monotherapy or in combination. In addition, the effect of the drugs on neutral lipid levels and the yeast ultrastructure were evaluated by flow cytometry and transmission electron microscopy (TEM), respectively. RESULTS: The MIC and MFC values show that clotrimazole was more effective than itraconazole against feline S. brasiliensis isolates, while human isolates were more sensitive to itraconazole. Similarly to itraconazole, treatment with clotrimazole induced statistically significant neutral lipid accumulation in S. brasiliensis yeasts, and treated yeasts displayed irregularities in the cell membrane and a thicker cell wall when observed by TEM. Clotrimazole increased the antifungal activity of itraconazole in combination assays, with a synergistic effect for two feline isolates. CONCLUSION: The strong activity of clotrimazole against feline S. brasiliensis isolates suggests that this drug is potentially a new alternative for the treatment of feline sporotrichosis, alone or in combination with itraconazole. PMID- 28984227 TI - Leprosy in pre-Norman Suffolk, UK: biomolecular and geochemical analysis of the woman from Hoxne. AB - PURPOSE: A woman's skull, exhibiting features of lepromatous leprosy (LL), was recovered from a garden in Hoxne, Suffolk. The absence of post crania and lack of formal excavation meant that diagnosis and dating was uncertain. The aim of this research was to confirm the diagnosis using biomolecular means and second, to place it in context with other British leprosy cases using SNP genotyping and radiocarbon dating. METHODOLOGY: Bone from the skull was analysed by ancient DNA (aDNA) methods and subjected to radiocarbon dating. As a result, stable carbon and nitrogen isotope values were produced, both useful for assessing aspects of the woman's diet.Results/Key findings. aDNA confirmed the presence of mycobacterium leprae and genotyping demonstrated an ancestral variant of subtype 3I, the same lineage recently identified in living squirrels in the south of England. Radiocarbon dating revealed the woman lived approximately between 885 1015 AD, providing evidence for endurance of this subtype in East Anglia, having been previously identified as early as the fifth-sixth century (Great Chesterford) and as late as the thirteenth century (Ipswich). CONCLUSIONS: The confirmation of a new pre-Norman leprosy case in East Anglia is of interest as this is where a high proportion of cases are located. Possible factors for this may include preservation and excavation biases, population density, but also connection and trade, possibly of fur, with the continent. Future research on other British LL cases should focus on exploring these aspects to advance understanding of the disease's history, here and on the continent. PMID- 28984228 TI - Substitutions at residues 300 and 389 of the VP2 capsid protein serve as the minimal determinant of attenuation for canine parvovirus vaccine strain 9985-46. AB - Identifying molecular determinants of virulence attenuation in live attenuated canine parvovirus (CPV) vaccines is important for assuring their safety. To this end, we identified mutations in the attenuated CPV 9985-46 vaccine strain that arose during serial passage in Crandell-Rees feline kidney cells by comparison with the wild-type counterpart, as well as minimal determinants of the loss of virulence. Four amino acid substitutions (N93K, G300V, T389N and V562L) in VP2 of strain 9985-46 significantly restricted infection in canine A72 cells. Using an infectious molecular clone system, we constructed isogenic CPVs of the parental virulent 9985 strain carrying single or double mutations. We observed that only a single amino acid substitution in VP2, G300V or T389N, attenuated the virulent parental virus. Combinations of these mutations further attenuated CPV to a level comparable to that of 9985-46. Strains with G300V/T389N substitutions did not induce clinical symptoms in experimentally infected pups, and their ability to infect canine cells was highly restricted. We found that another G300V/V562L double mutation decreased affinity of the virus for canine cells, although its pathogenicity to dogs was maintained. These results indicate that mutation of residue 300, which plays a critical role in host tropism, is not sufficient for viral attenuation in vivo, and that attenuation of 9985-46 strain is defined by at least two mutations in residues 300 and 389 of the VP2 capsid protein. This finding is relevant for quality control of the vaccine and provides insight into the rational design of second-generation live attenuated vaccine candidates. PMID- 28984230 TI - Markerless deletion of putative alanine dehydrogenase genes in Bacillus licheniformis using a codBA-based counterselection technique. AB - Bacillus licheniformis strains are used for the large-scale production of industrial exoenzymes from proteinaceous substrates, but details of the amino acid metabolism involved are largely unknown. In this study, two chromosomal genes putatively involved in amino acid metabolism of B. licheniformis were deleted to clarify their role. For this, a convenient counterselection system for markerless in-frame deletions was developed for B. licheniformis. A deletion plasmid containing up- and downstream DNA segments of the chromosomal deletion target was conjugated to B. licheniformis and integrated into the genome by homologous recombination. Thereafter, the counterselection was done by using a codBA cassette. The presence of cytosine deaminase and cytosine permease exerted a conditionally lethal phenotype on B. licheniformis cells in the presence of the cytosine analogue 5-fluorocytosine. Thereby clones were selected that lost the integrated vector sequence and the anticipated deletion target after a second recombination step. This method allows the construction of markerless mutants in Bacillus strains in iterative cycles. B. licheniformis MW3 derivatives lacking either one of the ORFs BL03009 or BL00190, encoding a putative alanine dehydrogenase and a similar putative enzyme, respectively, retained the ability to grow in minimal medium supplemented with alanine as the carbon source. In the double deletion mutant MW3 DeltaBL03009 DeltaBL00190, however, growth on alanine was completely abolished. These data indicate that the two encoded enzymes are paralogues fulfilling mutually replaceable functions in alanine utilization, and suggest that in B. licheniformis MW3 alanine utilization is initiated by direct oxidative transamination to pyruvate and ammonium. PMID- 28984229 TI - Development of macrolide resistance-associated mutations after macrolide treatment in children infected with Mycoplasma pneumoniae. AB - PURPOSE: To determine the timing of the emergence of macrolide-resistant mutations after macrolide treatment in individuals with Mycoplasma pneumoniae infections. METHODOLOGY: Between October 2011 and December 2013, serial pharyngeal swab specimens were collected before and after macrolide treatment from 21 otherwise healthy children infected with M. pneumoniae without macrolide resistant mutations. The copy numbers of a M. pneumoniae gene and the proportion of clones showing macrolide-resistance mutations were determined for each specimen. RESULTS: After macrolide treatment (10-15 mg kg-1 day-1 clarithromycin for 5-10 days or 10 mg kg-1 day-1 azithromycin for 3 days), fever resolved in 19 (90 %) of 21 children within 1 to 2 days, and the M. pneumoniae gene copy number decreased in all but one specimen in the second set of specimens relative to the number in the corresponding initial specimens. None of the second specimens, which were collected 2-4 days after initiation of macrolide treatment, showed mutations in the 23S rRNA gene. However, the proportion of mutant clones with A2063G and A2064G mutations in the specimens collected 7-24 days after initiation of treatment increased to 100 %. We identified a family in which three members had M. pneumoniae infections. The analysis of transmission in this household indicated that the M. pneumoniae harbouring a macrolide-resistant mutation that developed in the index patient after macrolide treatment was not transmitted to the family members. CONCLUSION: A macrolide-resistant population might develop in individual patients up to 24 days after initiation of macrolide treatment. However, the decrease in M. pneumoniae load after macrolide administration effectively reduces interpersonal transmission. PMID- 28984231 TI - Transgene expression in the genome of Middle East respiratory syndrome coronavirus based on a novel reverse genetics system utilizing Red-mediated recombination cloning. AB - Middle East respiratory syndrome coronavirus (MERS-CoV) is a high-priority pathogen in pandemic preparedness research. Reverse genetics systems are a valuable tool to study viral replication and pathogenesis, design attenuated vaccines and create defined viral assay systems for applications such as antiviral screening. Here we present a novel reverse genetics system for MERS-CoV that involves maintenance of the full-length viral genome as a cDNA copy inserted in a bacterial artificial chromosome amenable to manipulation by homologue recombination, based on the bacteriophage lambda Red recombination system. Based on a full-length infectious MERS-CoV cDNA clone, optimal genomic insertion sites and expression strategies for GFP were identified and used to generate a reporter MERS-CoV expressing GFP in addition to the complete set of viral proteins. GFP was genetically fused to the N-terminal part of protein 4a, from which it is released during translation via porcine teschovirus 2A peptide activity. The resulting reporter virus achieved titres nearly identical to the wild-type virus 48 h after infection of Vero cells at m.o.i. 0.001 (1*105 p.f.u. ml-1 and 3*105 p.f.u. ml-1, respectively), and allowed determination of the 50 % inhibitory concentration for the known MERS-CoV inhibitor cyclosporine A based on fluorescence readout. The resulting value was 2.41 uM, which corresponds to values based on wild-type virus. The reverse genetics system described herein can be efficiently mutated by Red-mediated recombination. The GFP-expressing reporter virus contains the full set of MERS-CoV proteins and achieves wild-type titres in cell culture. PMID- 28984232 TI - CHROMagar COL-APSE: a selective bacterial culture medium for the isolation and differentiation of colistin-resistant Gram-negative pathogens. AB - PURPOSE: A selective chromogenic culture medium for the laboratory isolation and differentiation of colistin resistant Acinetobacter, Pseudomonas, Stenotrophomonas and Enterobacteriaceae spp. (CHROMagar COL-APSE) was developed, evaluated and compared to an existing selective bacterial culture medium (SuperPolymyxin). METHODOLOGY: The medium was challenged with 84 isolates, including polymyxin B (POL B)-susceptible and -resistant type strains and colistin (COL)-resistant organisms recovered from human and animal samples. Susceptibility to COL and POL B was determined by agar dilution and broth microtitre dilution. The lower limit for the detection of COL-resistant organisms was also calculated for both CHROMagar COL-APSE and SuperPolymyxin media. The ability to isolate and correctly differentiate COL-resistant organisms within mixed cultures was also assessed and compared using both media. RESULTS: Using CHROMagar COL-APSE, Gram-negative pathogens (n=71) with intrinsic (n=8) or acquired COL (n=63) resistance were recovered with 100 % specificity down to the lower limit of detection of 101 colony-forming units (c.f.u.). The growth on SuperPolymyxin was similar, but notably weaker for COL-resistant non-fermentative bacteria (Acinetobacter, Pseudomonas and Stenotrophomonas). CHROMagar COL-APSE was also more sensitive in supporting the growth of Enterobacteriaceae with COL resistance associated with the carriage of mcr-1. CONCLUSION: CHROMagar COL-APSE is a sensitive and specific medium for the growth of COL-resistant bacterial pathogens. Due to the low limit of detection (101 c.f.u.), it may be useful as a primary isolation medium in the surveillance and recovery of COL-resistant bacteria from complex human, veterinary and environmental samples, especially those with plasmid-mediated MCR-1 or novel mechanisms of polymyxin resistance. PMID- 28984233 TI - Surface micropattern reduces colonization and medical device-associated infections. AB - PURPOSE: Surface microtopography offers a promising approach for infection control. The goal of this study was to provide evidence that micropatterned surfaces significantly reduce the potential risk of medical device-associated infections. METHODOLOGY: Micropatterned and smooth surfaces were challenged in vitro against the colonization and transference of two representative bacterial pathogens - Staphylococcus aureus and Pseudomonas aeruginosa. A percutaneous rat model was used to assess the effectiveness of the micropattern against device associated S. aureus infections. After the percutaneous insertion of silicone rods into (healthy or immunocompromised) rats, their backs were inoculated with S. aureus. The bacterial burdens were determined in tissues under the rods and in the spleens. RESULTS: The micropatterns reduced adherence by S. aureus (92.3 and 90.5 % reduction for flat and cylindrical surfaces, respectively), while P. aeruginosa colonization was limited by 99.9 % (flat) and 95.5 % (cylindrical). The micropatterned surfaces restricted transference by 95.1 % for S. aureus and 94.9 % for P. aeruginosa, compared to smooth surfaces. Rats with micropatterned devices had substantially fewer S. aureus in subcutaneous tissues (91 %) and spleens (88 %) compared to those with smooth ones. In a follow-up study, immunocompromised rats with micropatterned devices had significantly lower bacterial burdens on devices (99.5 and 99.9 % reduction on external and internal segments, respectively), as well as in subcutaneous tissues (97.8 %) and spleens (90.7 %) compared to those with smooth devices. CONCLUSION: Micropatterned surfaces exhibited significantly reduced colonization and transference in vitro, as well as lower bacterial burdens in animal models. These results indicate that introducing this micropattern onto surfaces has high potential to reduce medical device-associated infections. PMID- 28984234 TI - Stenotrophomonas maltophilia produces an EntC-dependent catecholate siderophore that is distinct from enterobactin. AB - Stenotrophomonas maltophilia, a Gram-negative, multi-drug-resistant bacterium, is increasingly recognized as a key opportunistic pathogen. Thus, we embarked upon an investigation of S. maltophilia iron acquisition. To begin, we determined that the genome of strain K279a is predicted to encode a complete siderophore system, including a biosynthesis pathway, an outer-membrane receptor for ferrisiderophore, and other import and export machinery. Compatible with these data, K279a and other clinical isolates of S. maltophilia secreted a siderophore like activity when grown at 25-37 degrees C in low-iron media, as demonstrated by a chrome azurol S assay, which detects iron chelation, and Arnow and Rioux assays, which detect catecholate structures. Importantly, these supernatants rescued the growth of iron-starved S. maltophilia, documenting the presence of a biologically active siderophore. A mutation in one of the predicted biosynthesis genes (entC) abolished production of the siderophore and impaired bacterial growth in low-iron conditions. Inactivation of the putative receptor gene (fepA) prevented the utilization of siderophore-containing supernatants for growth in low-iron conditions. Although the biosynthesis and import loci showed some similarity to those of enterobactin, a well-known catecholate made by enteric bacteria, the siderophore of K279a was unable to rescue the growth of an enterobactin-utilizing indicator strain, and conversely iron-starved S. maltophilia could not use purified enterobactin. Furthermore, the S. maltophilia siderophore displayed patterns of solubility in organic compounds and mobility upon thin-layer chromatography that were distinct from those of enterobactin and its derivative, salmochelin. Together, these data demonstrate that S. maltophilia secretes a novel catecholate siderophore. PMID- 28984236 TI - Siccirubricoccus deserti gen. nov., sp. nov., a proteobacterium isolated from a desert sample. AB - Strain SYSU D8009T was isolated from a desert sample collected from Saudi Arabia. The taxonomic position of the isolate was investigated by a polyphasic approach. The novel isolate was Gram-stain-negative, non-motile, aerobic and non-spore forming. It was able to grow at 4-45 degrees C and pH 4.0-8.0, and exhibited NaCl tolerance of up to 1.5 % (w/v). Strain SYSU D8009T shared the closest 16S rRNA gene sequence similarities with members of the family Acetobacteraceae, with a value of less than 96.0 %. In the phylogenetic dendrograms, the strain clustered with the genera Paracraurococcus, Craurococcus and Crenalkalicoccus within the family Acetobacteraceae but with a distinct lineage, thereby demonstrating that the strain should be classified within the family Acetobacteraceae. The respiratory ubiquinone was found to be Q-10. The polar lipids of the strain comprised diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol and four unidentified aminolipids. The predominant cellular fatty acids were summed feature 8 (C18 : 1omega7c and/or C18 : 1omega6c) and C16 : 0. The genomic DNA G+C content of strain SYSU D8009T was determined to be 71.6 mol%. Based on the results of the phylogenetic analyses and differences in the physiological and biochemical characteristics, strain SYSU D8009T merits representation of a novel species of a new genus within the family Acetobacteraceae, for which the name Siccirubricoccus deserti gen. nov., sp. nov. is proposed. The type strain of Siccirubricoccus deserti sp. nov. is SYSU D8009T (=CGMCC 1.15936T=KCTC 62088T). PMID- 28984237 TI - Aeribacillus composti sp. nov., a thermophilic bacillus isolated from olive mill pomace compost. AB - A Gram-stain-positive, aerobic, endospore-forming, thermophilic bacterium, strain N.8T, was isolated from the curing step of an olive mill pomace compost sample, collected at the Composting Experimental Centre (CESCO, Salerno, Italy). Strain N.8T, based on 16S rRNA gene sequence similarities, was most closely related to Aeribacillus pallidus strain H12T (=DSM 3670T) (99.8 % similarity value) with a 25 % DNA-DNA relatedness value. Cells were rod-shaped, non-motile and grew optimally at 60 degrees C and pH 9.0, forming cream colonies. Strain N.8 was able to grow on medium containing up to 9.0 % (w/v) NaCl with an optimum at 6.0 % (w/v) NaCl. The cellular membrane contained MK-7, and C16 : 0 (48.4 %), iso-C17 : 0 (19.4 %) and anteiso-C17 : 0 (14.6 %) were the major cellular fatty acids. The DNA G+C content was 40.5 mol%. Based on phenotypic characteristics, 16S rRNA gene sequences, DNA-DNA hybridization values and chemotaxonomic characteristics, strain N.8T represents a novel species of the genus Aeribacillus, for which the name Aeribacillus composti sp. nov. is proposed. The type strain is N.8T (=KCTC 33824T=JCM 31580T). PMID- 28984238 TI - Manipulation of both virus- and cell-specific factors is required for robust transient replication of a hepatitis C virus genotype 3a sub-genomic replicon. AB - Hepatitis C virus (HCV) genotype (GT) 3 is the second most prevalent of the seven HCV genotypes and exhibits the greatest resistance to the highly potent, direct acting antivirals (DAAs) that are currently in use. Previously a stable cell line harbouring the S52 GT3 sub-genomic replicon (SGR) was established, but this SGR was unable to robustly replicate transiently. As transient SGRs are a critical tool in the development of DAAs, and in the study of viral resistance, we sought to establish a transient SGR system based on S52. Next-generation sequencing was used to identify putative culture-adaptive substitutions that had arisen during long-term selection of the S52 SGR. A subset of these substitutions was built back into the S52 SGR in the context of a CpG/UpA-low luciferase reporter, with a single point mutation in NS4A conferring the greatest replication capability upon S52. Modification of the innate immune-sensing pathways of Huh7.5 hepatoma cells by expression of the parainfluenza virus type 5 V protein and SEC14L2 resulted in a further enhancement of S52 replication. Furthermore, this transiently replicating SGR showed genotype-specific differences in sensitivity to two clinically relevant NS5A DAAs. In conclusion, we report that a single substitution in NS4A, coupled with host cell modifications, enabled robust levels of transient replication by the GT3 S52 SGR. This system will have beneficial uses in both basic research into the unique aspects of GT3 biology and drug discovery. PMID- 28984239 TI - Variability of interferon-lambda induction and antiviral activity in Nipah virus infected differentiated human bronchial epithelial cells of two human donors. AB - Highly pathogenic Nipah virus (NiV) generally causes severe encephalitis in humans. Respiratory symptoms are infrequently observed, likely reflecting variations in infection kinetics in human airways. Supporting this idea, we recently identified individual differences in NiV replication kinetics in cultured airway epithelia from different human donors. As type III interferons (IFN-lambda) represent major players in the defence mechanism against viral infection of the respiratory mucosa, we studied IFN-lambda induction and antiviral activity in NiV-infected primary differentiated human bronchial epithelial cells (HBEpCs) cultured under air-liquid interface conditions. Our studies revealed that IFN-lambda was upregulated in airway epithelia upon NiV infection. We also show that IFN-lambda pretreatment efficiently inhibited NiV replication. Interestingly, the antiviral activity of IFN-lambda varied in HBEpCs from two different donors. Increased sensitivity to IFN-lambda was associated with higher expression levels of IFN-lambda receptors, enhanced phosphorylation of STAT1, as well as enhanced induction of interferon-stimulated gene expression. These findings suggest that individual variations in IFN-lambda receptor expression affecting IFN responsiveness can play a functional role for NiV replication kinetics in human respiratory epithelial cells of different donors. PMID- 28984240 TI - In vitro detection of bacterial contamination in platelet concentrates by matrix assisted laser desorption/ionization time-of-flight mass spectrometry: a preliminary study. AB - PURPOSE: Platelet concentrates are at risk of transfusion-related sepsis. The microbial detection methods currently available have reached their limits, as they do not completely prevent transfusion-related bacterial contamination.The aim of this study was to develop a new strategy to detect the risk of platelet transfusion-related bacterial contamination using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). METHODOLOGY: In vitro, platelet concentrates were seeded with known concentrations of bacterial strains. Protein mass profiles were acquired by using a Microflex MALDI-TOF instrument. Dedicated 'Platelet' software was used as a spectrum subtraction tool to reveal specific peaks caused by the presence of pathogens in samples. RESULTS: The MALDI-TOF spectra of platelets were characterized and the reproducibility over time, regardless of the blood donor, was demonstrated with a positive predictive value of 100 %. In addition, the negative predictive value of the total number of specific peaks to predict contamination was 100 %. CONCLUSION: Detecting bacteria in platelet concentrates using the MALDI-TOF approach and analysing spectra with the Platelet software present the advantage of combining the precocity of results and sufficient sensitivity (10 c.f.u. ml-1). Further research will be conducted to compare this novel method with the current conventional method in order to validate our results, the objective being to reduce the risk of platelet transfusion-related bacterial contamination. PMID- 28984241 TI - Identification of the same polyomavirus species in different African horseshoe bat species is indicative of short-range host-switching events. AB - Polyomaviruses (PyVs) are considered to be highly host-specific in different mammalian species, with no well-supported evidence for host-switching events. We examined the species diversity and host specificity of PyVs in horseshoe bats (Rhinolophus spp.), a broadly distributed and highly speciose mammalian genus. We annotated six PyV genomes, comprising four new PyV species, based on pairwise identity within the large T antigen (LTAg) coding region. Phylogenetic comparisons revealed two instances of highly related PyV species, one in each of the Alphapolyomavirus and Betapolyomavirus genera, present in different horseshoe bat host species (Rhinolophus blasii and R. simulator), suggestive of short-range host-switching events. The two pairs of Rhinolophus PyVs in different horseshoe bat host species were 99.9 and 88.8 % identical with each other over their respective LTAg coding sequences and thus constitute the same virus species. To corroborate the species identification of the bat hosts, we analysed mitochondrial cytb and a large nuclear intron dataset derived from six independent and neutrally evolving loci for bat taxa of interest. Bayesian estimates of the ages of the most recent common ancestors suggested that the near identical and more distantly related PyV species diverged approximately 9.1E4 (5E3-2.8E5) and 9.9E6 (4E6-18E6) years before the present, respectively, in contrast to the divergence times of the bat host species: 12.4E6 (10.4E6-15.4E6). Our findings provide evidence that short-range host-switching of PyVs is possible in horseshoe bats, suggesting that PyV transmission between closely related mammalian species can occur. PMID- 28984242 TI - Biochanin A partially restores the activity of ofloxacin and ciprofloxacin against topoisomerase IV mutation-associated fluoroquinolone-resistant Ureaplasma species. AB - PURPOSE: This study aims to investigate the synergistic antimicrobial activity of four phytoalexins in combination with fluoroquinolones against Ureaplasma spp., a genus of cell wall-free bacteria that are intrinsically resistant to many available antibiotics, making treatment inherently difficult. METHODOLOGY: A total of 22 958 urogenital tract specimens were assessed for Ureaplasma spp. identification and antimicrobial susceptibility. From these, 31 epidemiologically unrelated strains were randomly selected for antimicrobial susceptibility testing to determine the minimum inhibitory concentration (MIC) of four fluoroquinolones and the corresponding quinolone resistance-determining regions (QRDRs). Synergistic effects between fluoroquinolones and four phytoalexins (reserpine, piperine, carvacrol and biochanin A) were evaluated by fractional inhibitory concentration indices (FICIs). RESULTS: Analysis of the QRDRs suggested a vital role for the mutation of Ser-83->Leu in ParC in fluoroquinolone-resistant strains, and the occurrence of mutations in QRDRs showed significant associations with the breakpoint of levofloxacin. Moreover, diverse synergistic effects of the four phytoalexins with ofloxacin or ciprofloxacin were observed and biochanin A was able to enhance the antimicrobial activity of fluoroquinolones significantly. CONCLUSION: This is the first report of the antimicrobial activity of biochanin A in combination with fluoroquinolones against a pathogenic mycoplasma, and opens up the possibility of using components of biochanin A as a promising therapeutic option for treating antibiotic-resistant Ureaplasma spp. infections. PMID- 28984243 TI - Long-term health effects after resolution of acute Cryptosporidium parvum infection: a 1-year follow-up of outbreak-associated cases. AB - We describe a longitudinal study carried out in an adult outbreak-associated cohort to investigate health effects, including post-infectious irritable bowel syndrome, occurring after resolution of acute Cryptosporidium parvum infection. New symptoms self-reported up to 12 months included: weight loss (31 %), abdominal pain (38 %), diarrhoea (33 %), eye pain (9 %), joint pain (33 %), fatigue (22 %) and symptoms consistent with irritable bowel syndrome (IBS) (28 %). Two people were medically diagnosed with IBS. This study describes for the first time sequelae reported by patients up to 12 months after infection with C. parvum, which appear to be similar to those described with C. hominis. PMID- 28984245 TI - Competing scaffolding proteins determine capsid size during mobilization of Staphylococcus aureus pathogenicity islands. AB - Staphylococcus aureus pathogenicity islands (SaPIs), such as SaPI1, exploit specific helper bacteriophages, like 80alpha, for their high frequency mobilization, a process termed 'molecular piracy'. SaPI1 redirects the helper's assembly pathway to form small capsids that can only accommodate the smaller SaPI1 genome, but not a complete phage genome. SaPI1 encodes two proteins, CpmA and CpmB, that are responsible for this size redirection. We have determined the structures of the 80alpha and SaPI1 procapsids to near-atomic resolution by cryo electron microscopy, and show that CpmB competes with the 80alpha scaffolding protein (SP) for a binding site on the capsid protein (CP), and works by altering the angle between capsomers. We probed these interactions genetically and identified second-site suppressors of lethal mutations in SP. Our structures show, for the first time, the detailed interactions between SP and CP in a bacteriophage, providing unique insights into macromolecular assembly processes. PMID- 28984246 TI - The role of EEG in the diagnosis and classification of the epilepsy syndromes: a tool for clinical practice by the ILAE Neurophysiology Task Force (Part 1). AB - The concept of epilepsy syndromes, introduced in 1989, was defined as "clusters of signs and symptoms customarily occurring together". Definition of epilepsy syndromes based on electro-clinical features facilitated clinical practice and, whenever possible, clinical research in homogeneous groups of patients with epilepsies. Progress in the fields of neuroimaging and genetics made it rapidly clear that, although crucial, the electro-clinical description of epilepsy syndromes was not sufficient to allow much needed development of targeted therapies and a better understanding of the underlying pathophysiological mechanisms of seizures. The 2017 ILAE position paper on Classification of the Epilepsies recognized that "as a critical tool for the practicing clinician, epilepsy classification must be relevant and dynamic to changes in thinking". The concept of "epilepsy syndromes" evolved, incorporating issues related to aetiologies and comorbidities. A comprehensive update (and revision where necessary) of the EEG diagnostic criteria in the light of the 2017 revised terminology and concepts was deemed necessary. The work was commissioned by the Neurophysiology Task Force of the ILAE Committee on the Diagnostic Methods. Diagnostic criteria and recording procedures were developed by group consensus, reached through an "informal", internal decision-making process. Each working group member was allocated a number of syndromes, and a standard structured template was used. International literature was extensively reviewed. We developed a simple diagnostic system that is applicable to all epilepsy syndromes which allows the physician (i) to rate the strength of EEG diagnosis (degree of diagnostic certainty) by weighting EEG findings in relation to the available clinical information or the specific clinical question, and ii) to suggest further EEG diagnostics where conclusive diagnostic evidence is lacking. We also propose a system of syndrome-specific recording protocols that, used with the relevant clinical presentation or specific clinical question, may maximize activation of epileptic discharges and ultimately help with standardization of EEG recording across departments, worldwide. Because recording methodology also depends on available resources, a two-tier system was developed to embrace clinical EEG services in resource-limited and industrialized countries. A clinical practice statement for each of the epilepsy syndromes discussed underscores the crucial role of the clinical information with regards to both the optimization of the EEG recording and mainly its meaningful interpretation. Part I covers Genetic (Idiopathic) generalized epilepsies and syndromes, Reflex epilepsies, structural and genetic focal (lobar) syndromes and Progressive Myoclonus Epilepsies [Published with educational EEG plates on www.epilepticdisorders.com]. PMID- 28984235 TI - Biochemical Features of Beneficial Microbes: Foundations for Therapeutic Microbiology. AB - Commensal and beneficial microbes secrete myriad products which target the mammalian host and other microbes. These secreted substances aid in bacterial niche development, and select compounds beneficially modulate the host and promote health. Microbes produce unique compounds which can serve as signaling factors to the host, such as biogenic amine neuromodulators, or quorum-sensing molecules to facilitate inter-bacterial communication. Bacterial metabolites can also participate in functional enhancement of host metabolic capabilities, immunoregulation, and improvement of intestinal barrier function. Secreted products such as lactic acid, hydrogen peroxide, bacteriocins, and bacteriocin like substances can also target the microbiome. Microbes differ greatly in their metabolic potential and subsequent host effects. As a result, knowledge about microbial metabolites will facilitate selection of next-generation probiotics and therapeutic compounds derived from the mammalian microbiome. In this article we describe prominent examples of microbial metabolites and their effects on microbial communities and the mammalian host. PMID- 28984247 TI - Organ Donation in Children: The Next Frontier. PMID- 28984244 TI - YTHDC1 mediates nuclear export of N6-methyladenosine methylated mRNAs. AB - N6-methyladenosine (m6A) is the most abundant internal modification of eukaryotic messenger RNA (mRNA) and plays critical roles in RNA biology. The function of this modification is mediated by m6A-selective 'reader' proteins of the YTH family, which incorporate m6A-modified mRNAs into pathways of RNA metabolism. Here, we show that the m6A-binding protein YTHDC1 mediates export of methylated mRNA from the nucleus to the cytoplasm in HeLa cells. Knockdown of YTHDC1 results in an extended residence time for nuclear m6A-containing mRNA, with an accumulation of transcripts in the nucleus and accompanying depletion within the cytoplasm. YTHDC1 interacts with the splicing factor and nuclear export adaptor protein SRSF3, and facilitates RNA binding to both SRSF3 and NXF1. This role for YTHDC1 expands the potential utility of chemical modification of mRNA, and supports an emerging paradigm of m6A as a distinct biochemical entity for selective processing and metabolism of mammalian mRNAs. PMID- 28984249 TI - Inflammatory Bowel Disease-Unclassified: How Much do we Know? PMID- 28984248 TI - Antibiotic Consumption and Consequence: Lessons from the Neonatal Units. PMID- 28984250 TI - Pediatric Rhabdomyosarcoma in India: A Single-center Experience. AB - OBJECTIVE: Analyze the profile and outcome of children with rhabdomyosarcoma from a pediatric-oncology unit. DESIGN: Retrospective analysis of case records over 23 years (1990-2012). Setting: Government-run, tertiary-care, university hospital in Northern India. PARTICIPANTS: 159 children (<12-years) with a diagnosis of rhabdomyosarcoma were enrolled. The median age was 4 years; 13% were infants. MAIN OUTCOME MEASURE: Five-year event free survival. RESULTS: The median symptom interval was 2-months. Head and neck region was the most frequent site (44%), followed by tumors in the extremity (15.7%). The majority (67%) of the tumors were located at 'unfavorable' sites; 68% were >5 cm in size. The most frequent (58%) pathological subtype was embryonal. Treatment was based on the 'Intergroup Rhabdomyosarcoma Study (IRS) Group' risk-stratification. 33% were 'low-risk' children, 11% were 'high-risk'. Treatment-refusal (18%) and abandonment (33%) were major impediments. The median +/- SE five-year event free survival of those taking treatment was 43.6 +/- 6%. Conclusion: Large sized tumors, tumors at unfavorable locations, and treatment refusal/abandonment contributed to inferior outcome in children with rhabdomyosarcoma. PMID- 28984251 TI - Impact of Antibiotic Policy on Antibiotic Consumption in a Neonatal Intensive Care Unit in India. AB - OBJECTIVE: To study the impact of initiating antibiotic policy on antibiotic consumption in a neonatal intensive care unit (NICU). METHODS: This retrospective study was conducted between January, 2013 and December, 2014 in a 30 bed NICU. The antibiotic policy for neonatal sepsis was initiated on January 1st, 2014. The overall antibiotic consumption (Daily Defined Dose [DDD] per 100 patient-days), one year before and one year after the initiation of antibiotic policy was evaluated using interrupted time-series analysis. RESULTS: There was no significant change (12.47 vs. 11.47 DDD/100 patient-days; P = 0.57) in overall antibiotic consumption. A significant increase in the proportion of patients on first-line agents (ampicillin and gentamicin) (66% (n=449) vs. 84% (n=491); P <0.001) and significant decrease in consumption of third generation cephalosporins (1.45 vs. 0.45 DDD/100 patient-days; P =0.002) was observed. Conclusion: Antibiotic policy increased the use of first-line agents and decreased the consumption of third generation cephalosporins. PMID- 28984252 TI - Long-term Outcome of Inflammatory Bowel Disease-Unclassified in Children. AB - OBJECTIVE: To document the frequency at diagnosis and evolution over time of inflammatory bowel disease-unclassified in children. METHODS: Analysis of case records (2004-2011) of patients diagnosed with inflammatory bowel disease unclassified following upper-gastrointestinal endoscopy, ileocolonoscopy and small bowel imaging. Any subsequent diagnostic reclassification by 2016 was recorded. RESULTS: 344 children diagnosed as inflammatory bowel disease: 58% Crohn's disease, 34.5% ulcerative colitis, and 7.5% (n=26) inflammatory bowel disease-unclassified. 25/26 inflammatory bowel disease-unclassified patients were followed for 4.5-11.5 years. 17 of these patients needed endoscopic re-evaluation leading to changed diagnosis in ten (Crohn's disease 7, ulcerative colitis 3). Conclusion: 7.5% (25/344) of inflammatory bowel disease children had inflammatory bowel disease-unclassified at diagnosis; 10 (40%) evolved into Crohn's disease or ulcerative colitis. PMID- 28984253 TI - Evaluation of Asthma Control in Children Using Childhood- Asthma Control Test (C ACT) and Asthma Therapy Assessment Questionnaire (ATAQ). AB - OBJECTIVE: To evaluate the efficacy of Childhood-asthma control test (C-ACT) and the Asthma therapy assessment questionnaire by (ATAQ) checking its consistency with Global Initiative for Asthma (GINA) criteria. METHODS: Asthma control of 97 children was assessed using C-ACT, ATAQ and GINA criteria separately, and their results were compared. RESULTS: C-ACT had better performance for evaluating control as per GINA criteria with sensitivity of 48.3%, specificity of 68.9%, and area under the receiver operative curve (ROC) of 0.647. The above parameters for ATAQ were: 93.1%, 17.2% and 0.552, respectively. A cut-off score of 20 for C-ACT is more suitable as it has maximum ROC area (0.667), and higher kappa score (0.315); P= 0.001. Conclusion: C-ACT can be validity used to monitor asthma control. However, the cut-off score 20 is more accurate for the Indian population. The performance of ATAQ in evaluating asthma control is not satisfactory. PMID- 28984254 TI - Yield of Imaging Performed as per Indian Society of Pediatric Nephrology Guidelines in Children with Urinary Tract Infection. AB - OBJECTIVE: To assess yield of imaging performed as per Indian Society of Pediatric Nephrology (ISPN) urinary tract infection (UTI) guideline. METHODS: Ultrasonography (USG), voiding cystourethrography (VCUG) and dimercaptosuccinic acid (DMSA) scintigraphy were performed in 183 children (age 0-5y) with first episode (age 0-1y) of UTI or recurrent (age <5y) UTI, as per ISPN recommendations. RESULTS: Significant abnormalities were detected in 110 (63%), with vesicoureteric reflux (VUR) grades 3-5 in 31% and renal scars in 43%. Combined USG and DMSA had a negative predictive value of 94% for significant VUR. Conclusion: ISPN guideline resulted in a high yield of detection of significant abnormalities. PMID- 28984255 TI - Risk Factors for Cardiovascular Disease in Obese Children. AB - OBJECTIVE: To study the prevalence of cardiovascular risk factors in pediatric obesity. METHODS: 50 obese children (age 5-17y) and 50 apparently healthy non obese children (body mass index of over 95th percentile and between 5th to 95th percentiles, respectively) using Centre for Disease Control growth charts were included. Fasting blood sugar, lipid profile, insulin, homeostasis model assessment of insulin resistance, uric acid, fibrinogen, lipoprotein (a), homocysteine, malondialdehyde, ferric reducing ability of plasma and nitric oxide were measured. RESULTS: Insulin, insulin resistance, triglycerides, uric acid, fibrinogen, malondialdehyde, ferric reducing ability of plasma and nitric oxide were significantly higher (P <0.001) in obese children. Body mass index showed significant positive correlation with insulin r=0.519, P<0.001; insulin resistance r =0.479, P<0.001; uric acid r= 0.289, P=0.005; fibrinogen r=0.461, P<0.001; and nitric oxide r=0.235, P=0.012. Conclusion: Pediatric obesity is associated with dyslipidemia, oxidative stress, insulin resistance and endothelial dysfunction, which are cardiovascular risk factors and components of metabolic syndrome. These children must be targeted for lifestyle and dietary modification. PMID- 28984256 TI - Neonatal Endocrine Labomas - Pitfalls and Challenges in Reporting Neonatal Hormonal Reports. AB - This review highlights pitfalls and challenges in interpreting neonatal hormone reports. Pre-analytical errors contribute to nearly 50% of all errors. Modern chemiluminescence assay are more accurate, have lower risk of Hook's effect, but continue to have problems of assay interference. Liquid chromatography mass spectroscopy is gold standard for most hormone assays. Neonatal hypoglycemia diagnostic cut-offs are lower than adults. Random growth hormone testing is of value in diagnosing growth hormone deficiency in neonates. 17-hydroxy progesterone testing in first three days of life for congenital adrenal hyperplasia (CAH) remains a challenge due to cross-reactivity with maternal circulating steroids, prematurity and lack of adrenal maturation. Both T4 and TSH testing is encouraged after 48 hours of delivery for diagnosing neonatal hypothyroidism; repeat testing should be done immediately for confirmation of diagnosis. There is an urgent need to develop age- sex- and ethnicity-based normative data for different hormone parameters in neonates. Laboratory should develop their own neonatal references and avoid using ranges from manufacturers. In neonatal endocrinopathies, the clinical scenario should primarily dictate the treatment formulation with hormonal assay to supplement treatment. PMID- 28984257 TI - From Kwashiorkor to Edematous Malnutrition. PMID- 28984258 TI - Hepatic Sinusoidal-obstruction Syndrome and Busulfan-induced Lung Injury in a Post-autologous Stem Cell Transplant Recipient. AB - Veno-occlusive disease of the liver is mostly encountered as a complication of hematopoietic stem cell transplantation with myeloablative regimens with an incidence estimated to be 13.7%. It is clinically characterized by tender hepatomegaly, jaundice, weight gain and ascites. Strong clinical suspicion and an early recognition of clinical signs are essential to establish the diagnosis and institute effective regimen. Another complication of cytotoxic drugs given for cancers, is development of busulfan-induced lung injury. A strong index of suspicion is needed for its diagnosis, especially in setting where opportunistic fungal and viral infections manifest similarly. We illustrate the clinical and autopsy finings in a 21/2-year-old boy who received autologous stem-cell transplantation following resection of stage IV neuroblastoma. He subsequently developed both hepatic veno-occlusive disease and busulfan-induced lung injury. The autopsy findings are remarkable for their rarity. PMID- 28984259 TI - Maternal Pseudo-Bartter Syndrome Associated with Severe Perinatal Brain Injury. AB - BACKGROUND: Maternal electrolyte imbalance is rarely reported as causative factor of severe perinatal brain injury. CASE CHARACTERISTICS: This case outlines a unique maternal and neonatal pseudo-Bartter syndrome presented with metabolic alkalosis and hypochloremia due to maternal severe vomiting. OBSERVATION: Neonatal MRI brain revealed extensive brain hemorrhages with porencephalic cysts. Subsequent investigation workup points towards maternal severe metabolic alkalosis as its cause. MESSAGE: Careful medical attention should be paid to pregnant women with excessive vomiting to ensure a healthy outcome for both the mother and the baby. PMID- 28984260 TI - Glycogen Storage Disease Type VI With a Novel Mutation in PYGL Gene. AB - BACKGROUND: Glycogen storage disease type VI (GSD-VI) presents with failure to thrive and also fibrosis in some cases, without cirrhosis. CASE CHARACTERISTICS: 21/2-year-old girl presented with short stature, transaminase elevation and significant fibrosis, suggesting GSD-III. OBSERVATION: A pathogenic mutation in PYGL gene suggested GSD-VI. MESSAGE: GSD-VI should be a differential diagnosis whenever GSD-III is suspected. PMID- 28984261 TI - Factors Affecting Outcome in Children with Dengue in Kolkata. AB - This observational, descriptive study was conducted on 260 dengue patients diagnosed as per the revised 2009 WHO guidelines in a tertiary-care hospital of eastern India between June and November 2015. Children were evaluated for clinical symptoms, signs, and laboratory parameters. Clinical variables viz., rash, nausea/vomiting, bleeding, oliguria, capillary leak and liver enlargement; and laboratory variables viz., rising haemoglobin, haematocrit, thrombocytopenia, blood urea, serum Creatinine, ALT, hypo albuminemia and cholesterol were found to be significantly associated with outcome. PMID- 28984262 TI - The Unusual Story of an Infant with Congenital Adrenal Hyperplasia. PMID- 28984263 TI - Evisceration of Gut Through Post-surgical Drain Site in a Neonate. PMID- 28984264 TI - Simultaneous Two Site Blood Culture in Diagnosis of Neonatal Sepsis: Few Concerns. PMID- 28984265 TI - Simultaneous Two Site Blood Culture in Diagnosis of Neonatal Sepsis: Few Concerns: Authors Reply. PMID- 28984266 TI - Quantum Jump in the Coverage of Mega Doses of Vitamin A Supplementation Program to Children in India. PMID- 28984267 TI - Cotrimoxazole-induced Methemoglobinemia. PMID- 28984268 TI - Autistic Regression: Should it Prompt Urgent EEG? PMID- 28984269 TI - Family-Centered Care: Beginning of a New Era in India. PMID- 28984270 TI - Family-Centered Care: Beginning of a New Era in India: Authors Reply. PMID- 28984271 TI - When are we to Integrate 'Research Module' in Undergraduate Medical Curriculum in India? PMID- 28984272 TI - Clinical Trials: A Step Closer to Universal Data Sharing. PMID- 28984273 TI - Coarsening of carbon black supported Pt nanoparticles in hydrogen. AB - This study addresses coarsening mechanisms of Pt nanoparticles supported on carbon black in hydrogen. By means of in situ transmission electron microscopy (TEM), Pt nanoparticle coarsening was monitored in 6 mbar 20% H2/Ar while ramping up the temperature to almost 1000 degrees C. Time-resolved TEM images directly reveal that separated ca. 3 nm sized Pt nanoparticles in a hydrogen environment are stable up to ca. 800 degrees C at a heating rate of 10 degrees C min-1. The coarsening above this temperature is dominated by the particle migration and coalescence mechanism. However, for agglomerated Pt nanoparticles, coalescence events were observed already above 200 degrees C. The temperature-dependency of particle sizes and the observed migration distances are described and found to be consistent with simple early models for the migration and coalescence. PMID- 28984274 TI - Nonclassical nucleation pathways in protein crystallization. AB - Classical nucleation theory (CNT), which was established about 90 years ago, has been very successful in many research fields, and continues to be the most commonly used theory in describing the nucleation process. For a fluid-to-solid phase transition, CNT states that the solute molecules in a supersaturated solution reversibly form small clusters. Once the cluster size reaches a critical value, it becomes thermodynamically stable and favored for further growth. One of the most important assumptions of CNT is that the nucleation process is described by one reaction coordinate and all order parameters proceed simultaneously. Recent studies in experiments, computer simulations and theory have revealed nonclassical features in the early stage of nucleation. In particular, the decoupling of order parameters involved during a fluid-to-solid transition leads to the so-called two-step nucleation mechanism, in which a metastable intermediate phase (MIP) exists between the initial supersaturated solution and the final crystals. Depending on the exact free energy landscapes, the MIPs can be a high density liquid phase, mesoscopic clusters, or a pre-ordered state. In this review, we focus on the studies of nonclassical pathways in protein crystallization and discuss the applications of the various scenarios of two-step nucleation theory. In particular, we focus on protein solutions in the presence of multivalent salts, which serve as a model protein system to study the nucleation pathways. We wish to point out the unique features of proteins as model systems for further studies. PMID- 28984275 TI - Electric control of the bandgap in quantum wells with band-inverted junctions. AB - In IV-VI semiconductor heterojunctions with band-inversion, such as those made of [Formula: see text] [Formula: see text]Te or [Formula: see text] [Formula: see text]Se, interface states are properly described by a two-band model, predicting the appearance of a Dirac cone in single junctions. However, in quantum wells the interface dispersion is quadratic in momentum and the energy spectrum presents a gap. We show that the interface gap shrinks under an electric field parallel to the growth direction. Therefore, the interface gap can be dynamically tuned in experiments on double-gated quantum wells based on band-inverted compounds. PMID- 28984276 TI - Role of charged impurities in thermoelectric transport in molybdenum disulfide monolayers. AB - A theoretical study of the electronic properties, namely, electrical conductivity (EC), electronic thermal conductivity (ETC) and thermoelectric power (TEP) in 2D MoS2 monolayers (MLs), over a wide range of temperatures (10 < T < 300 K), is presented employing Boltzmann transport formalism. Considering the electrons to be scattered by screened charged impurities and the acoustic, optical and remote phonons, the transport equation is solved using Ritz iterative method. Numerical calculations of EC, ETC and TEP presented for supported and free-standing MLs with high electron concentrations, as a function of temperature, bring out the relative importance of the various scattering mechanisms operative. The role of CIs, with regard to both concentration and separation from the substrate-ML interface, in determining the properties of supported MLs is demonstrated for the first time. Validity of Wiedemann-Franz law and Mott formula are examined for supported and free standing MLs. Calculations are in consonance with recent experimental data on mobility and TEP of exfoliated SiO2-supported MoS2 ML samples. In the case of TEP it is found that though the diffusion contribution is dominant the inclusion of the drag component, incorporating contributions from all relevant phonon scattering mechanisms, is needed to obtain good agreement with the data. PMID- 28984277 TI - A multicentre audit of HDR/PDR brachytherapy absolute dosimetry in association with the INTERLACE trial (NCT015662405). AB - A UK multicentre audit to evaluate HDR and PDR brachytherapy has been performed using alanine absolute dosimetry. This is the first national UK audit performing an absolute dose measurement at a clinically relevant distance (20 mm) from the source. It was performed in both INTERLACE (a phase III multicentre trial in cervical cancer) and non-INTERLACE brachytherapy centres treating gynaecological tumours. Forty-seven UK centres (including the National Physical Laboratory) were visited. A simulated line source was generated within each centre's treatment planning system and dwell times calculated to deliver 10 Gy at 20 mm from the midpoint of the central dwell (representative of Point A of the Manchester system). The line source was delivered in a water-equivalent plastic phantom (Barts Solid Water) encased in blocks of PMMA (polymethyl methacrylate) and charge measured with an ion chamber at 3 positions (120 degrees apart, 20 mm from the source). Absorbed dose was then measured with alanine at the same positions and averaged to reduce source positional uncertainties. Charge was also measured at 50 mm from the source (representative of Point B of the Manchester system). Source types included 46 HDR and PDR 192Ir sources, (7 Flexisource, 24 mHDR-v2, 12 GammaMed HDR Plus, 2 GammaMed PDR Plus, 1 VS2000) and 1 HDR 60Co source, (Co0.A86). Alanine measurements when compared to the centres' calculated dose showed a mean difference (+/-SD) of +1.1% (+/-1.4%) at 20 mm. Differences were also observed between source types and dose calculation algorithm. Ion chamber measurements demonstrated significant discrepancies between the three holes mainly due to positional variation of the source within the catheter (0.4% 4.9% maximum difference between two holes). This comprehensive audit of absolute dose to water from a simulated line source showed all centres could deliver the prescribed dose to within 5% maximum difference between measurement and calculation. PMID- 28984278 TI - Spin reorientation and disordered rare earth magnetism in Ho2FeCoO6. AB - We report the experimental observation of spin reorientation in the double perovskite Ho2FeCoO6. The magnetic phase transitions in this compound are characterized and studied through magnetization and specific heat, and the magnetic structures are elucidated through neutron powder diffraction. Two magnetic phase transitions are observed in this compound - one at TN1 ~ 250 K, from paramagnetic to antiferromagnetic, and the other at TN2 ~ 45 K, from a phase with mixed magnetic structures to a single phase through a spin reorientation process. The magnetic structure in the temperature range 200 K -45 K is a mixed phase of the irreducible representations Gamma1 and Gamma3, both of which are antiferromagnetic. The phase with mixed magnetic structures that exists in Ho2FeCoO6 gives rise to a large thermal hysteresis in magnetization that extends from 200 K down to the spin reorientation temperature. At TN2, the magnetic structure transforms to Gamma1. Though long-range magnetic order is established in the transition metal lattice, it is seen that only short-range magnetic order prevails in Ho3+ - lattice. Our results should motivate further detailed studies on single crystals in order to explore spin reorientation process, spin switching and the possibility of anisotropic magnetic interactions giving rise to electric polarization in Ho2FeCoO6. PMID- 28984281 TI - Comment on "Calcium preparations do not inhibit allergic reactions: a randomized controlled trial". PMID- 28984282 TI - Cardiac implantable electronic device infection: formidable, frustrating, and increasingly frequent. PMID- 28984283 TI - High-sensitivity troponin T as a prognostic marker in patients undergoing aortic valve replacement. PMID- 28984285 TI - Large mass on the mitral valve in a woman in the 28th week of pregnancy. PMID- 28984284 TI - Acute pancreatitis due to an attack of acute intermittent porphyria. PMID- 28984286 TI - Acute coronary syndrome with a culprit lesion in a single coronary artery. PMID- 28984288 TI - Preanalytical, analytical, and postanalytical errors in the measurement of irisin levels. PMID- 28984287 TI - The LifeVest wearable defibrillator for noninvasive prevention of sudden arrhythmic death syndrome. The first Polish case of an adequate LifeVest intervention. PMID- 28984289 TI - Preanalytical, analytical, and postanalytical errors in the measurement of irisin levels. Authors' reply. PMID- 28984290 TI - Role of autophagy in oncolytic herpes simplex virus type 1-induced cell death in squamous cell carcinoma cells. AB - Herpes simplex virus type 1 (HSV-1) is one of the most widely studied viruses for oncolytic virotherapy. In squamous cell carcinoma (SCC) cells, the role of autophagy induced by neurovirulence gene-deficient HSV-1s in programmed cell death has not yet been elucidated. The oncolytic HSV-1 strain RH2, which lacks the gamma34.5 gene and induces the fusion of human SCC cells, was used. RH2 replicated and induced cell death in SCC cells. RH2 infection was accompanied by the aggregation of microtubule-associated protein 1 light chain 3 (LC3) in the cytoplasm, the conversion of LC3-I to LC3-II and the formation of double-membrane vacuoles containing cell contents. No significant changes were observed in the expression of Bcl-2 or Bax, while a slight decrease was observed in that of Beclin 1. The autophagy inhibitors, 3-methyladenine (3-MA) and bafilomycin A1, did not affect viral replication, but significantly inhibited the cytotoxicity of RH2. The caspase-3 inhibitor z-DEVD-fmk and caspase-1 inhibitor z-YVAD-fmk also reduced the cytotoxicity of RH2. These results demonstrated that gamma34.5 gene deficient HSV-1 RH2 induced autophagic cell death in SCC cells as well as pyroptosis and apoptosis. PMID- 28984292 TI - Immunotherapy: CD8+ T cells - burn fat, get fit. PMID- 28984291 TI - New perspectives for targeting RAF kinase in human cancer. AB - The discovery that a subset of human tumours is dependent on mutationally deregulated BRAF kinase intensified the development of RAF inhibitors to be used as potential therapeutics. The US Food and Drug Administration (FDA)-approved second-generation RAF inhibitors vemurafenib and dabrafenib have elicited remarkable responses and improved survival of patients with BRAF-V600E/K melanoma, but their effectiveness is limited by resistance. Beyond melanoma, current clinical RAF inhibitors show modest efficacy when used for colorectal and thyroid BRAF-V600E tumours or for tumours harbouring BRAF alterations other than the V600 mutation. Accumulated experimental and clinical evidence indicates that the complex biochemical mechanisms of RAF kinase signalling account both for the effectiveness of RAF inhibitors and for the various mechanisms of tumour resistance to them. Recently, a number of next-generation RAF inhibitors, with diverse structural and biochemical properties, have entered preclinical and clinical development. In this Review, we discuss the current understanding of RAF kinase regulation, mechanisms of inhibitor action and related clinical resistance to these drugs. The recent elucidation of critical structural and biochemical aspects of RAF inhibitor action, combined with the availability of a number of structurally diverse RAF inhibitors currently in preclinical and clinical development, will enable the design of more effective RAF inhibitors and RAF inhibitor-based therapeutic strategies, tailored to different clinical contexts. PMID- 28984294 TI - Perinatal Immune Activation Produces Persistent Sleep Alterations and Epileptiform Activity in Male Mice. AB - Increasing evidence suggests a role for inflammation in neuropsychiatric conditions, including autism spectrum disorder (ASD). Previous work in rodents has established that immune activation during critical developmental periods can cause phenotypes that reproduce core features of ASD, including decreased social interaction, aberrant communication, and increased repetitive behavior. In humans, ASD is frequently associated with comorbid medical conditions including sleep disorders, motor hyperactivity, and seizures. Here we use a 'two-hit' immune-activation paradigm to determine whether perinatal immune activation can also produce these comorbid features in mice. In this paradigm, we treated timed pregnant mice with polyinosinic:polycytidylic acid (Poly I:C), which simulates a viral infection, on gestational day 12.5 according to an established maternal immune activation regimen. A subset of the offspring also received a second 'hit' of lipopolysaccharide (LPS), which simulates a bacterial infection, on postnatal day 9. At 6 weeks of age, mice were implanted with wireless telemetry transmitters that enabled continuous measurements of electroencephalography (EEG), electromyography (EMG), locomotor activity, and subcutaneous temperature. Effects at 7 and 12 weeks of age were compared. Both prenatal Poly I:C and postnatal LPS produced changes in locomotor activity and temperature patterns, increases in slow-wave sleep, and shifts in EEG spectral power, several of which persisted at 12 weeks of age. Postnatal LPS also produced persistent increases in spontaneous bursts of epileptiform activity (spike-wave discharges) that occurred predominantly during sleep. Our findings demonstrate that early-life immune activation can lead to long-lasting physiologic perturbations that resemble medical comorbidities often seen in ASD and other neuropsychiatric conditions. PMID- 28984293 TI - Drive and Reinforcement Circuitry in the Brain: Origins, Neurotransmitters, and Projection Fields. AB - Brain stimulation has identified two central subsets of stimulation sites with motivational relevance. First, there is a large and disperse set of sites where stimulation is reinforcing, increasing the frequency of the responses it follows, and second, a much more restricted set of sites where-along with reinforcement stimulation also has drive-like effects, instigating feeding, copulation, predation, and other motivated acts in otherwise sated or peaceful animals. From this work a dispersed but synaptically interconnected network of reinforcement circuitry is emerging: it includes afferents to the ventral tegmental area and substantia nigra; the dopamine systems themselves; glutamatergic afferents to the striatum; and one of two dopamine-receptor-expressing efferent pathways of the striatum. Stimulation of a limited subset of these sites, including descending inhibitory medial forebrain bundle fibers, induces both feeding and reinforcement, and suggests the possibility of a subset of fibers where stimulation has both drive-like and reinforcing effects. This review stresses the common findings of sites and connectivity between electrical and optogenetic studies of core drive and reinforcement sites. By doing so, it suggests the biological importance of optogenetic follow-up of less-publicized electrical stimulation findings. Such studies promise not only information about origins, neurotransmitters, and connectivity of related networks, by covering more sensory and at least one putative motor component they also promote a much deeper understanding of the breadth of motivational function. PMID- 28984295 TI - R-Baclofen Reverses Cognitive Deficits and Improves Social Interactions in Two Lines of 16p11.2 Deletion Mice. AB - Human chromosome 16p11.2 microdeletion is among the most common gene copy number variations (CNVs) known to confer risk for intellectual disability (ID) and autism spectrum disorder (ASD) and affects an estimated 3 in 10 000 people. Caused by a single copy deletion of ~27 genes, 16p11.2 microdeletion syndrome is characterized by ID, impaired language, communication and socialization skills, and ASD. Studies in animal models where a single copy of the syntenic 16p11.2 region has been deleted have revealed morphological, behavioral, and electrophysiological abnormalities. Previous studies suggested the possibility of some overlap in the mechanisms of pathophysiology in 16p11.2 microdeletion syndrome and fragile X syndrome. Improvements in fragile X phenotypes have been observed following chronic treatment with R-baclofen, a selective agonist of GABAB receptors. We were therefore motivated to investigate the effects of chronic oral R-baclofen administration in two independently generated mouse models of 16p11.2 microdeletion syndrome. In studies performed across two independent laboratories, we found that chronic activation of GABAB receptors improved performance on a series of cognitive and social tasks known to be impaired in two different 16p11.2 deletion mouse models. Our findings suggest that R-baclofen may have clinical utility for some of the core symptoms of human 16p11.2 microdeletion syndrome. PMID- 28984296 TI - Male breast cancer: correlation between immunohistochemical subtyping and PAM50 intrinsic subtypes, and the subsequent clinical outcomes. AB - Male breast cancer is a rare disease that is still poorly understood. It is mainly classified by immunohistochemistry as a luminal disease. In this study, we assess for the first time the correlation between molecular subtypes based on a validated six-marker immunohistochemical panel and PAM50 signature in male breast cancer, and the subsequent clinical outcome of these different subtypes. We collected 67 surgical specimens of invasive male breast cancer from four different Spanish pathology laboratories. Immunohistochemical staining for the six-marker panel was performed on tissue microarrays. PAM50 subtypes were determined in a research-use-only nCounter Analysis System. We explored the association of immunohistochemical and PAM50 subtypes. Overall survival and disease-free survival were analyzed in the different subtypes of each classification. The distribution of tumor molecular subtypes according PAM50 was: 60% luminal B, 30% luminal A and 10% human epidermal growth factor receptor 2 (Her2) enriched. Only one Her2-enriched tumor was also positive by immunohistochemistry and was treated with trastuzumab. None of the tumors were basal-like. Using immunohistochemical surrogates, 51% of the tumors were luminal B, 44% luminal A, 4% triple-negative and 1% Her2-positive. The clinicopathological characteristics did not differ significantly between immunohistochemical and PAM50 subtypes. We found a significant worse overall survival in Her2-enriched compared with luminal tumors. Male breast cancer seems to be mainly a genomic luminal disease with a predominance of the luminal B subtype. In addition, we found a proportion of patients with Her2-negative by immunohistochemistry but Her2-enriched profile by PAM50 tumors with a worse outcome compared with luminal subtypes that may benefit from anti-Her2 therapies. PMID- 28984297 TI - Expression patterns of class I histone deacetylases in osteosarcoma: a novel prognostic marker with potential therapeutic implications. AB - Epigenetic aberrations are recognized as having pivotal roles in cancer etiology and progression. Histone deacetylases are among the most studied epigenetic modulators in various cancer types. The expression levels of class I histone deacetylase isoforms 1, 2, and 3 in patient-derived primary osteosarcoma cells (6 cases) was investigated, comparing them to normal bone graft-derived osteoblasts (6 cases) using the immunoblotting technique. Expression profiles of histone deacetylases in high-grade osteosarcoma tissue of 89 patients were examined and their association with clinicopathologic parameters and the patient survival was evaluated. Histone deacetylases were immunohistochemically stained on formalin fixed paraffin-embedded biopsied tissue. Primary osteosarcoma cells expressed higher levels of histone deacetylase 1 and histone deacetylase 2, but lower levels of histone deacetylase 3 compared to benign osteoblasts. Overall, 82, 99, and 93% of 89 osteosarcomas showed nuclear expression of the histone deacetylase isoforms 1, 2, and 3, respectively. Low levels of histone deacetylase 1 were significantly associated with a high Enneking stage (P=0.014) and the presence of initial metastasis (P=0.040), while low levels of histone deacetylase 3 were significantly correlated with age >15 years (P=0.026). Univariate survival analysis found significantly shorter survival in the patients with a high Enneking stage (P<0.001), axial location (P=0.009), presence of initial metastasis (P<0.001), low-histone deacetylase 1 expression (P=0.038), and low-all histone deacetylases expression (P=0.016). Multivariate survival analysis showed that only axial location (P=0.011) and low-all-histone deacetylases expression (P=0.039) were independent prognostic factors. In subgroup analysis of stage IIB patients (n=45), only axial location and low-all-histone deacetylases expression were associated with shorter survival in both univariate and multivariate analysis (axial location, P=0.008 and 0.010; low-all-HDACs, P=0.013 and 0.038, respectively). Low levels of all-histone deacetylases expression were significantly associated with advanced disease status and short survival. These findings may be a guide to future use of histone deacetylase inhibitors in osteosarcoma patients. PMID- 28984298 TI - Polypoid fibroadipose tumors of the esophagus: 'giant fibrovascular polyp' or liposarcoma? A clinicopathological and molecular cytogenetic study of 13 cases. AB - Giant fibrovascular polyp of the esophagus is a descriptive diagnostic term intended to encompass rare, large, polypoid esophageal masses composed of fibroadipose tissue. Despite sometimes dramatic clinical presentations, they have historically been considered to represent reactive, non-neoplastic proliferations. Recently, however, a small number of reports have described well differentiated liposarcomas of the esophagus, mimicking giant fibrovascular polyps. In order to clarify the relationship between esophageal liposarcoma and giant fibrovascular polyp, we retrieved esophageal cases coded as 'giant fibrovascular polyp,' 'lipoma' and 'liposarcoma' from our archives and re examined their clinicopathologic features and MDM2 amplification status. Thirteen cases were identified (lipoma (n=1), giant fibrovascular polyp (n=5), well differentiated liposarcoma (n=3), dedifferentiated liposarcoma (n=3)). The tumors ranged from 5.2 to 19.5 cm and arose predominantly in the cervical esophagus. All consisted chiefly of mature adipose tissue, with a variable component of fibrous septa. In all cases, close inspection of these fibrous septa showed them to contain an increased number of slightly enlarged spindled cells with irregular, hyperchromatic nuclei, similar to those seen in some well-differentiated liposarcomas. Three cases, all previously classified as dedifferentiated liposarcoma, showed in addition solid zones of non-lipogenic spindle cell sarcoma. By fluorescence in situ hybridization (FISH), all cases showed MDM2 amplification, confirming diagnoses as well-differentiated (N=10) and dedifferentiated (N=3) liposarcoma. Clinical follow-up (8 cases, range 22-156 months, median 33 months) showed 3 patients with local recurrences (1 well differentiated and 2 dedifferentiated liposarcomas), 1 patient with liver metastases (dedifferentiated liposarcoma) and 2 deaths from disease (both dedifferentiated liposarcomas). These results suggest that the great majority of large, polypoid, fat-containing masses of the esophagus represent well and dedifferentiated liposarcoma, rather than 'giant fibrovascular polyps.' We suggest that the diagnosis of 'giant fibrovascular polyp' should be made with great caution in the esophagus, and only after careful morphological study and MDM2 FISH has excluded the possibility of liposarcoma. PMID- 28984299 TI - Medical renal diseases are frequent but often unrecognized in adult autopsies. AB - Kidney diseases affect many hospitalized patients and contribute to morbidity and mortality. Therefore, kidney disease should be prevalent, but the frequency and spectrum of medical renal pathology in autopsy specimens has not been well documented. We sought to determine the spectrum of medical renal pathology in adult autopsy specimens and the frequency of overlooked diagnoses. We reviewed the hematoxylin- and eosin-stained kidney sections from 140 adult autopsies performed at a large teaching hospital over a 2-year period. Fifty-eight cases (41%) had findings warranting further analysis, including alterations in glomerular matrix and/or cellularity, atypical or pigmented casts, thrombi, tubulointerstitial or vascular inflammation, or deposition of amorphous material. After additional studies and clinical correlation, the pathologic changes in 43 cases (31%) were categorized as follows: diabetic nephropathy, bile cast nephropathy, thrombotic microangiopathy, infection-related glomerulonephritis, focal necrotizing/crescentic glomerulonephritis, oxalate nephropathy, light-chain cast nephropathy, amyloidosis, urate nephropathy, hemosiderosis, antineutrophil cytoplasmic antibody-associated vasculitis, polyoma virus nephropathy, atheroembolic disease, and nephrocalcinosis. These diagnoses were not reported in 26 (60%) cases during the initial autopsy evaluation. This study demonstrates that medical renal diseases are common in autopsy cases, but significant diagnoses can be easily overlooked. Autopsy kidney specimens are a rich source of renal pathology and their evaluation should be emphasized in anatomic pathology residency training. Ultimately, our understanding of how kidney disease contributes to morbidity and mortality will benefit from accurate recognition of renal pathology in autopsy specimens. PMID- 28984300 TI - CD200 expression in mantle cell lymphoma identifies a unique subgroup of patients with frequent IGHV mutations, absence of SOX11 expression, and an indolent clinical course. AB - CD200, a marker currently utilized in the diagnosis of B-cell lymphoma, is uniformly positive in chronic lymphocytic leukemia/chronic lymphocytic leukemia, and is usually absent in mantle cell lymphoma. Over a 6 year-period, of 668 mantle cell lymphoma assessed by flow cytometry, CD200 expression was detected in 25 patients (~4%). All 25 patients had bone marrow involvement; however, 11 (44%) patients had no nodal or extranodal disease and belonged to non-nodal leukemic variant mantle cell lymphoma. Morphologically, bone marrow showed an unusual interstitial infiltrative pattern in 14/25 (56%) and small round cells resembling chronic lymphocytic leukemia in 9/25 (36%). CD23 was positive in 19/25 (76%) patients; and SOX11 was only positive in 5/21(24%). All 4 patients tested showed IGHV mutations. With a median follow-up of 23 months, 12/24 (50%) patients were not treated. These clinicopathological features were significantly different from 154 randomly chosen CD200-negative mantle cell lymphoma patients, in SOX11 positivity (24% versus 74%, P<0.0001), CD23 expression (76% versus 8%, P<0.0001), a non-nodal leukemic presentation (44% versus 2%, P<0.001), and therapy requirement (50% versus 92%, P<0.0001). This is the first study to show that CD200 expression in mantle cell lymphoma, though uncommon, identifies a subgroup of mantle cell lymphoma patients with characteristic pathological features, frequent non-nodal leukemic variant, and an indolent clinical course. PMID- 28984301 TI - Are the uterine serous carcinomas underdiagnosed? Histomorphologic and immunohistochemical correlates and clinical follow up in high-grade endometrial carcinomas initially diagnosed as high-grade endometrioid carcinoma. AB - Histologic subclassification of high-grade endometrial carcinomas can sometimes be a diagnostic challenge when based on histomorphology alone. Here we utilized immunohistochemical markers to determine the immunophenotype in histologically ambiguous high-grade endometrial carcinomas that were initially diagnosed as pure or mixed high-grade endometrioid carcinoma, aiming to determine the utility of selected immunohistochemical panel in accurate classification of these distinct tumor types, while correlating these findings with the clinical outcome. A total of 43 high-grade endometrial carcinoma cases initially classified as pure high grade endometrioid carcinoma (n=32), mixed high-grade endometrioid carcinoma/serous carcinoma (n=9) and mixed high-grade endometrioid carcinoma/clear cell carcinoma (n=2) were retrospectively stained with a panel of immunostains, including antibodies for p53, p16, estrogen receptor, and mammaglobin. Clinical follow-up data were obtained, and stage-to-stage disease outcomes were compared for different tumor types. Based on aberrant staining for p53 and p16, 17/43 (40%) of the high-grade endometrial carcinoma cases initially diagnosed as high-grade endometrioid carcinoma were re-classified as serous carcinoma. All 17 cases showed negative staining for mammaglobin, while estrogen receptor was positive in only 6 (35%) cases. The remaining 26 cases of high-grade endometrioid carcinoma showed wild-type staining for p53 in 25 (96%) cases, patchy staining for p16 in 20 (77%) cases, and were positive for mammaglobin and estrogen receptor in 8 (31%) and 19 (73%) cases, respectively, thus the initial diagnosis of high-grade endometrioid carcinoma was confirmed in these cases. In addition, the patients with re-classified serous carcinoma had advanced clinical stages at diagnosis and poorer overall survival on clinical follow-up compared to that of the remaining 26 high-grade endometrioid carcinoma cases. These results indicate that selected immunohistochemical panel, including p53, p16, and mammaglobin can be helpful in reaching accurate diagnosis in cases of histomorphologically ambiguous endometrial carcinomas, and can assist in providing guidance for appropriate therapeutic options for the patients. PMID- 28984302 TI - Composite analysis of immunological and metabolic markers defines novel subtypes of triple negative breast cancer. AB - Cancer biology is influenced by the tumor microenvironment, which impacts disease prognosis and therapeutic interventions. The inter-relationship of tumor infiltrating lymphocytes, immune response regulators, and a glycolytic tumor environment was evaluated in a cohort of 183 largely consecutive patients with triple negative breast cancer diagnosis. High levels of tumor-infiltrating lymphocytes were associated with improved survival of triple negative breast cancer cases. However, elevated levels of PD-L1, CD163, and FOXP3 were individually associated with significantly decreased overall survival. These three determinants were significantly correlated, and could serve to differentiate the prognostic significance of tumor-infiltrating lymphocytes. Interestingly, a glycolytic tumor environment, as determined by the expression of MCT4 in the tumor stroma, was associated with the immune evasive environment and poor prognosis. Clustering of all markers defined four distinct triple negative breast cancer subtypes that harbored prognostic significance in multivariate analysis. Immune and metabolic markers stratified triple negative breast cancer into subtypes that have prognostic significance and implications for therapies targeting immune checkpoints and tumor metabolism. PMID- 28984303 TI - Analysis of clinically relevant somatic mutations in high-risk head and neck cutaneous squamous cell carcinoma. AB - Cutaneous squamous cell carcinoma is the second most prevalent malignancy, most frequently occurring in the head and neck (head and neck cutaneous squamous cell carcinoma). Treatment of locally advanced or metastatic disease is associated with functional morbidity and disfigurement. Underlying genetic mechanisms are poorly understood. Targeted sequencing of 48 clinically relevant genes was performed on DNA extracted from formalin-fixed and paraffin-embedded high-risk primary head and neck cutaneous squamous cell carcinomas that remained non metastatic at minimum follow-up of 24 months. Associations of somatic mutations with clinicopathologic characteristics were evaluated and compared with those described in the literature for metastatic disease. Alterations in 44 cancer associated genes were identified. TP53 was mutated in 100% of cases; APC, ATM, ERBB4, GNAQ, KIT, RB1 and ABL1 were altered in 60% of cases. FGFR2 mutations (40%) were exclusively seen in patients with perineural invasion. MLH1 mutations were exclusively seen in the two younger patients (<45 years). Lower incidences of NOTCH1 mutations were observed compared with that described in metastatic head and neck cutaneous squamous cell carcinoma in the literature. Somatic mutations susceptible to EGFR inhibitors, and other small molecular targeted therapeutics were seen in 60% of cases. This study provides insights into somatic mutations in non-metastatic, high-risk head and neck cutaneous squamous cell carcinoma and identifies potential therapeutic targets. Alterations in FGFR2 and NOTCH1 may have roles in local and distant disease progression. PMID- 28984305 TI - Optoelectronics: Letting photons out of the gate. PMID- 28984304 TI - Clinicopathological and genomic analysis of double-hit follicular lymphoma: comparison with high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements. AB - Most high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements are aggressive B-cell lymphomas. Occasional double-hit follicular lymphomas have been described but the clinicopathological features of these tumors are not well known. To clarify the characteristics of double-hit follicular lymphomas, we analyzed 10 cases of double-hit follicular lymphomas and 15 cases of high-grade B cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements for clinicopathological and genome-wide copy-number alterations and copy-neutral loss of-heterozygosity profiles. For double-hit follicular lymphomas, the median age was 67.5 years (range: 48-82 years). The female/male ratio was 2.3. Eight patients presented with advanced clinical stage. The median follow-up time was 20 months (range: 1-132 months). At the end of the follow-up, 8 patients were alive, 2 patients were dead including 1 patient with diffuse large B-cell lymphoma transformation. Rearrangements of MYC/BCL2, MYC/BCL6, and MYC/BCL2/BCL6 were seen in 8, 1, and 1 cases, respectively. The partner of MYC was IGH in 6 cases. There were no cases of histological grade 1, 4 cases of grade 2, 5 cases of grade 3a, and 1 case of grade 3b. Two cases of grade 3a exhibited immunoblast-like morphology. Immunohistochemistry demonstrated 9 cases with >=50% MYC-positive cells. There was significant difference in MYC intensity (P=0.00004) and MIB-1 positivity (P=0.001) between double-hit follicular lymphomas and high-grade B cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements. The genome profile of double-hit follicular lymphomas was comparable with conventional follicular lymphomas (GSE67385, n=198) with characteristic gains of 2p25.3-p11.1, 7p22.3 q36.3, 12q11-q24.33, and loss of 18q21.32-q23 (P<0.05). In comparison with high grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements, double-hit follicular lymphomas had fewer copy-number alterations and minimal common region of gain at 2p16.1 (70%), locus also significant against conventional follicular lymphomas (P=0.0001). In summary, double-hit follicular lymphomas tended to be high-grade histology, high MYC protein expression, high MYC/IGH fusion, and minimal common region of gain at 2p16.1. Double-hit follicular lymphomas seemed to be a different disease from high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements and have an indolent clinical behavior similar to follicular lymphomas without MYC rearrangement. PMID- 28984307 TI - Students step up. PMID- 28984309 TI - Science outreach in the post-truth age. PMID- 28984308 TI - Science policy in the days of Trump. PMID- 28984311 TI - Spin qubits: Germanium-vacancy defects join the family. PMID- 28984310 TI - Towards phase-coherent caloritronics in superconducting circuits. AB - The emerging field of phase-coherent caloritronics (from the Latin word calor, heat) is based on the possibility of controlling heat currents by using the phase difference of the superconducting order parameter. The goal is to design and implement thermal devices that can control energy transfer with a degree of accuracy approaching that reached for charge transport by contemporary electronic components. This can be done by making use of the macroscopic quantum coherence intrinsic to superconducting condensates, which manifests itself through the Josephson effect and the proximity effect. Here, we review recent experimental results obtained in the realization of heat interferometers and thermal rectifiers, and discuss a few proposals for exotic nonlinear phase-coherent caloritronic devices, such as thermal transistors, solid-state memories, phase coherent heat splitters, microwave refrigerators, thermal engines and heat valves. Besides being attractive from the fundamental physics point of view, these systems are expected to have a vast impact on many cryogenic microcircuits requiring energy management, and possibly lay the first stone for the foundation of electronic thermal logic. PMID- 28984312 TI - Corrigendum: Monitoring the orientation of rare-earth-doped nanorods for flow shear tomography. AB - This corrects the article DOI: 10.1038/nnano.2017.111. PMID- 28984314 TI - Alzheimer disease: ApoE4 implicated in tau-mediated neurodegeneration. PMID- 28984313 TI - Human models of migraine - short-term pain for long-term gain. AB - Migraine is a complex disorder characterized by recurrent episodes of headache, and is one of the most prevalent and disabling neurological disorders. A key feature of migraine is that various factors can trigger an attack, and this phenomenon provides a unique opportunity to investigate disease mechanisms by experimentally inducing migraine attacks. In this Review, we summarize the existing experimental models of migraine in humans, including those that exploit nitric oxide, histamine, neuropeptide and prostaglandin signalling. We describe the development and use of these models in the discovery of molecular pathways that are responsible for initiation of migraine attacks. Combining experimental human models with advanced imaging techniques might help to identify biomarkers of migraine, and in the ongoing search for new and better migraine treatments, human models will have a key role in the discovery of future targets for more specific and more-effective mechanism-based antimigraine drugs. PMID- 28984316 TI - Is evidence-based practice a sinking ship? PMID- 28984317 TI - Pharmacotherapy: A smarter way to treat obesity. PMID- 28984318 TI - Diabetes: Risk of kidney disease in T1DM. PMID- 28984315 TI - PET imaging of the neurovascular interface in cerebrovascular disease. AB - Cerebrovascular disease encompasses a range of pathologies that affect different components of the cerebral vasculature and brain parenchyma. Large artery atherosclerosis, acute cerebral ischaemia, and intracerebral small vessel disease all demonstrate altered metabolic processes that are key to their pathogenesis. Although structural imaging techniques such as MRI are the mainstay of clinical care and research in cerebrovascular disease, they have limited ability to detect these pathophysiological processes in vivo. By contrast, PET can detect and quantify metabolic processes that are relevant to each facet of cerebrovascular disease. Information obtained from PET studies has helped to shape the understanding of key concepts in cerebrovascular medicine, including vulnerable atherosclerotic plaque, salvageable ischaemic penumbra, neuroinflammation and selective neuronal loss after ischaemic insult. PET has also helped to elucidate the relationships between chronic hypoxia, neuroinflammation, and amyloid-beta deposition in cerebral small vessel disease. This Review describes how PET-based imaging of metabolic processes at the neurovascular interface has contributed to our understanding of cerebrovascular disease. PMID- 28984320 TI - The first organocatalytic, ortho-regioselective inverse-electron-demand hetero Diels-Alder reaction. AB - The development of the unprecedented ortho-regioselective inverse-electron-demand hetero-Diels-Alder (IEDHDA) reaction is described. It has been demonstrated that by proper choice of reactants and reaction conditions the inverse-electron-demand hetero-Diels-Alder cycloaddition can be realized with unprecedented regioselectivity arising from the reaction between the terminal carbon atom of the dienophile and the heteroatom of the heterodiene. PMID- 28984321 TI - The cytotoxicity and mechanism of action of new multinuclear Scaffold AuIII, PdII pincer complexes containing a bis(diphenylphosphino) ferrocene/non-ferrocene ligand. AB - New multinuclear gold(iii), palladium(ii) pincer complexes containing bis(diphenylphosphino) ferrocene/non-ferrocene ligands of formula [(L)Au(MU2-eta2 CS3)Pd(dppf)](PF6)2, 1, and [(L)Au(MU2-eta2-CS3)Pd(dppe)](PF6)2, 2 (HL = 5 methoxy-1,3-bis (1-methyl-1H-benzo[d]imidazol-2-yl)benzene, dppf = 1,1' bis(diphenylphosphino)ferrocene, and dppe = bis(diphenylphosphino)ethane) have been synthesized and fully characterized. Both complexes are more cytotoxic to a number of human cancer cell lines than cisplatin. Moreover, complex 1 is more active than auranofin as the reference gold compound against a panel of several human tumor cell lines. Chemosensitivity tests completed on cisplatin sensitive and resistant cell lines have confirmed that both complexes were able to overcome cisplatin resistance. The complexes successfully inhibited the enzymes thioredoxin reductase (TrxR) and glutathione reductase (GR). The cellular uptake of both gold and palladium of the complexes was studied, which indicated a high biological stability of the complexes. The complexes 1 and 2 increase the production of ROS in HCT-15 cells. In addition, these complexes induce major levels of cancer cell death by apoptosis. PMID- 28984319 TI - Angiopoietin-like 3 in lipoprotein metabolism. AB - Triglycerides and cholesterol circulate in the bloodstream as part of various lipoprotein particles. Three members of the angiopoietin-like (ANGPTL) protein family - ANGPTL3, ANGPTL4 and ANGPTL8 - have emerged as important regulators of plasma lipoprotein levels by inhibiting the enzyme lipoprotein lipase. Here, I review the role of ANGPTL3 in lipoprotein metabolism. In contrast to ANGPTL4 and ANGPTL8, ANGPTL3 is exclusively produced in the liver and can therefore be classified as a true hepatokine. ANGPTL3 cooperates with ANGPTL8 to inhibit lipoprotein lipase and is mostly active after feeding, whereas ANGPTL4 is mostly active after fasting. Inactivation of ANGPTL3 in mice reduces plasma triglyceride and free fatty acid levels and suppresses atherosclerosis. In humans, homozygous loss-of-function mutations in ANGPTL3 lead to low plasma levels of low-density lipoproteins, high-density lipoproteins and triglycerides, a condition referred to as familial combined hypolipidaemia. Heterozygous carriers of loss-of-function mutations in ANGPTL3 have a lower risk of coronary artery disease than non carriers. At present, researchers are investigating antisense oligonucleotide and monoclonal antibody-based inactivation of ANGPTL3 in human clinical trials for the therapeutic management of dyslipidaemia and atherosclerosis. Thus, ANGPTL3 is an important liver-derived regulator of lipoprotein metabolism that holds considerable promise as a target for atherosclerosis. PMID- 28984322 TI - Nanocrystals generated under tensile stress in metallic glasses with phase selectivity. AB - Revealing the mechanism of phase selectivity can provide guidance for controlling crystals with certain phases for special properties. In the present work, nanocrystals of about 2-4 nm diameters with a B2 structure (thermodynamic metastable phase) are generated from CuZr glassy fiber by applying tensile stress at ambient temperature. By combining the ab initio calculations with the molecular dynamics simulations, the stabilities of B2 austenite and B19' martensitic phases under applied tensile stress are compared, and the phase transformation mechanism is revealed. The results show that the B2 structure has a bigger attractive basin, and the phase transition could occur with a larger applied stress during the deformation. Therefore, insights into the higher symmetric B2 nanocrystal with selective nucleation driven under directional stress are provided. PMID- 28984323 TI - Analysis of human gliomas by swab touch spray-mass spectrometry: applications to intraoperative assessment of surgical margins and presence of oncometabolites. AB - Touch spray mass spectrometry using medical swabs is an ambient ionization technique (ionization of unprocessed sample in the open air) that has potential intraoperative application in quickly identifying the disease state of tissue and in better characterizing the resection margin. To explore this potential, we studied 29 human brain tumor specimens and obtained evidence that this technique can provide diagnostic molecular information that is relevant to brain cancer. Touch spray using medical swabs involves the physical sampling of tissue using a medical swab on a spatial scale of a few mm2 with subsequent ionization occurring directly from the swab tip upon addition of solvent and application of a high voltage. Using a tertiary mixture of acetonitrile, N,N-dimethylformamide, and ethanol, membrane-derived phospholipids and oncometabolites are extracted from the tissue, incorporated into the sprayed microdroplets, vacuumed into the mass spectrometer, and characterized in the resulting mass spectra. The tumor cell load was assessed from the complex phospholipid pattern in the mass spectra and also separately by measurement of N-acetylaspartate. Mutation status of the isocitrate dehydrogenase gene was determined via detection of the oncometabolite 2-hydroxyglutarate. The lack of sample pretreatment makes touch spray mass spectrometry using medical swabs a feasible intraoperative strategy for rapid surgical assessment. PMID- 28984324 TI - Dynamics of the crystal structure of tin-based type-I clathrates with different degrees of disorder in their cationic frameworks. AB - The temperature dependencies of heat capacity, CP(T), and cubic unit cell parameter, a(T), were experimentally obtained in the range of 2-300 K for the compounds Sn24P19.2I8, Sn20Zn4P20.8I8, and Sn17Zn7P22I8, which belong to a family of type-I clathrates. The experimental data were analyzed in the frames of the Debye-Einstein approximation, further accounting for the contributions of positional disorder in the clathrate frameworks as well as those of defect modes arising from the distribution of guest atoms over unequal in energy but close in space positions inside the framework cages. By fitting the experimental data, the Debye and Einstein characteristic temperatures describing the dynamics of the framework and guest atoms, respectively, were obtained. Their analysis revealed peculiar dependencies of the characteristic temperatures upon the number of substituted zinc atoms and the concentration of vacancies in the framework, which are discussed in this paper. PMID- 28984326 TI - Thiol-ene synthesis and characterization of lithium bis(malonato)borate single ion conducting gel polymer electrolytes. AB - The development of high capacity anodes and high voltage cathodes for advanced lithium-ion batteries motivates the search for new polymer electrolytes that exhibit superior electrochemical stabilities and high ionic conductivities. We report a convenient, three-step synthesis of lithium bis(non-8-enyl malonato)borate (LiBNMB) as a alpha,omega-diene monomer, which undergoes thermally initiated thiol-ene crosslinking polymerizations in propylene carbonate to yield gel polymer electrolytes with high lithium ion concentrations (~0.9 M). By conducting these crosslinking polymerizations using mixtures of di- and tri thiols and LiBNMB with [thiol] : [ene] = 1 : 1, we synthesized a series of gel networks with dynamic elastic moduli ranging from G' = 40-79 kPa that increase monotonically with trifunctional crosslinker content. While ionic conductivities for these polymer gels measured by electrochemical impedance spectroscopy at 22 degrees C are sigma = 0.82-2.5 * 10-6 S cm-1, we show that the conductivity of propylene carbonate-solvated lithium ions though the bulk of these gel electrolytes is 8.5 * 10-5 S cm-1 independent of crosslinker density. However, the conductivities of the gel interfaces depend sensitively on crosslinker content, suggesting the importance of segmental rearrangement dynamics at the electrode interface in limiting the rate of ion motion. Thus, the design of highly conductive polymer electrolytes for advanced batteries demands careful design of both the internal and interfacial properties of these new materials. PMID- 28984325 TI - Synthesis of kinase inhibitors containing a pentafluorosulfanyl moiety. AB - A series of 3-methylidene-1H-indol-2(3H)-ones substituted with a 5- or 6 pentafluorosulfanyl group has been synthesized by a Knoevenagel condensation reaction of SF5-substituted oxindoles with a range of aldehydes. The resulting products were characterized by X-ray crystallography studies and were tested for biological activity versus a panel of cell lines and protein kinases. Some exhibited single digit nM activity. PMID- 28984327 TI - Probing photoinduced electron-transfer in graphene-dye hybrid materials for DSSC. AB - We investigated the photophysical properties of a newly synthesized hybrid material composed of a triphenylamine dye covalently bound to reduced graphene oxide, potentially relevant as a stable photosensitizer in dye-sensitized solar cells. The photophysical characterization has been carried out by means of fluorescence quenching and fluorescence lifetime measurements, complemented by Electron Paramagnetic Resonance (EPR) spectroscopy, aimed at the detailed description of the photoinduced processes occurring in the hybrid and in the mixed hybrid/N-doped TiO2 material. The combined optical/magnetic study unequivocally demonstrates a fast quenching of the dye excited state in the isolated hybrid and an efficient electron transfer to N-doped titania nanopowders. In the latter case, a metastable radical cation on the dye moiety is photogenerated and the corresponding negative charge, an electron, is trapped in defect sites of the doped semiconductor oxide. The spin distribution in the stable radical has been determined by EPR spectroscopy and correlated with DFT calculations. PMID- 28984328 TI - NMR effective radius of hydrogen in XIV group hydrides evaluated by NMR spectroscopy. AB - In the [ABrnIm] (A = C, Si, Ge, Sn; n + m = 4) compounds, with the heavier halides bonded to the central IV group elements, the experimental 13C, 29Si, 73Ge and 119Sn NMR chemical shifts of the central atoms were found to be strictly linearly proportional to the bonded halides ionic radii overall sum ?(rh). Based on this, calibration lines relating the chemical shifts to ?(rh) could be built for the considered subgroup of [ABrnIm] compounds. Using such calibration lines we could calculate the equivalent NMR radius, NMRrH-A, attributable to each of the bonded hydrogens in [AH4] species, according to the overall NMR shielding produced on the central A atom. Interestingly, the calculated NMRrH-A value resulted to be almost constant in all [AH4] examined systems (A = 13C, 29Si, 73Ge, 119Sn) with an average NMRr[combining macron]H-A value equal to 194.6 +/- 1.6 pm. Based on this approach, we could calculate the 207Pb NMR chemical shift of the unstable [PbH4] complex using the value of 192.7 pm calculated for NMRrH Sn in the stable closest hydride [SnH4]. The obtained unprecedented NMR value is in accord with the 207Pb NMR chemical shift estimation, independently calculated for [PbH4] from the [SnH4] data, using the Pb/Sn chemical shift correlation defined in the Mitchell equation. PMID- 28984329 TI - A water-soluble two-photon ratiometric triarylboron probe with nucleolar targeting by preferential RNA binding. AB - By functionalizing triarylboron with cyclen, we developed a two-photon fluorescence probe, TAB-2, which can selectively bind RNA with a ratiometric readout. We tested TAB-2 in NIH/3T3 fibroblast cells, and demonstrated its capability in visualizing nucleoli and analyzing microenvironment polarity by two photon and fluorescence-lifetime imaging microscopy. PMID- 28984331 TI - Excited-states of a rhenium carbonyl diimine complex: solvation models, spin orbit coupling, and vibrational sampling effects. AB - We present a quantum-chemical investigation of the excited states of the complex [Re(CO)3(Im)(Phen)]+ (Im = imidazole; Phen = 1,10-phenanthroline) in solution including spin-orbit couplings and vibrational sampling. To this aim, we implemented electrostatic embedding quantum mechanics/molecular mechanics (QM/MM) in the Amsterdam Density Functional program suite, suitable for time-dependent density functional calculations including spin-orbit couplings. The new implementation is employed to simulate the absorption spectrum of the complex, which is compared to the results of implicit continuum solvation and frozen density embedding. Molecular dynamics simulations are used to sample the ground state conformations in solution. The results demonstrate that any study of the excited states of [Re(CO)3(Im)(Phen)]+ in solution and their dynamics should include extensive sampling of vibrational motion and spin-orbit couplings. PMID- 28984332 TI - Visualizing and quantifying the nanoscale hydrophobicity and chemical distribution of surface modified polyethersulfone (PES) membranes. AB - Chemical modifications bring unique properties into polymeric membranes that may have enhanced filtration or separation efficiencies, antifouling, antimicrobial activity and selectivity. However, there is a lack of nanoscale characterization of the chemical additive distribution and the impacts of chemical modifiers or additives on membrane surface properties, especially those at the nanoscale. In this study, a series of industrially relevant polyethersulfone (PES) membranes modified with poly (ethylene glycol) (PEG) and polyvinylpyrrolidone (PVP) were analysed systematically. Particularly, hydrophobicity and chemical distribution were scrutinized by atomic force microscopy (AFM) and AFM coupled with infrared analysis capability (AFM-IR) for the first time that successfully resolved nanoscale structural and chemical properties of the chemically modified PES membranes. Our results indicated the heterogeneous spatial distribution of PVP and PEG based on their characteristic IR bands and the resulting hydrophobicity distribution on modified membrane surfaces at the nanoscale. Particularly, we established a linear correlation (R2 = 0.9449) between the measured adhesion force and water contact angles, which enabled the examination of local surface hydrophobicity. The PES membranes became more hydrophilic with the increasing blend of PVP and PEG. With AFM-IR, trace amounts (1-4%) of PVP could be identified sensitively on PES membranes based on their unique characteristic IR bands, which were not achieved by FTIR or IR mapping. Overall, these novel characterization approaches hold paramount importance for the design and quality control of polymer membrane modification and manufacturing. PMID- 28984330 TI - An unsymmetric cisplatin-based Pt(iv) derivative containing 2-(2 propynyl)octanoate: a very efficient multi-action antitumor prodrug candidate. AB - The design, synthesis, characterization and biological properties of a Pt(iv) complex containing the very active inhibitor of histone deacetylase (2 propynyl)octanoic acid, POA, as an axial ligand are reported here. The title complex, namely (OC-6-44)-acetatodiamminedichlorido(2-(2 propynyl)octanoato)platinum(iv), 1, containing POA in racemic or in enantiomeric forms, was one/two orders of magnitude more active than cisplatin, depending on the chemo-sensitivity of the cancer cell lines. Moreover, 1 exhibited similar or even better antiproliferative activity than (OC-6-33)-diamminedichloridobis(2 propylpentanoato)platinum(iv), 2, containing two molecules of the well-known histone deacetylase inhibitor 2-propylpentanoic (valproic) acid. The high potency of 1 is likely due to its high cellular accumulation and to the synergism between the DNA-damaging cisplatin and the histone deacetylase inhibitor POA, both released upon the intracellular reduction of 1. Prodrug 1, after oral administration, caused an impressive reduction of the tumor mass (94%) in a model of solid tumor (murine Lewis lung carcinoma), compared to that of the control, whereas (intraperitoneal) cisplatin induced a tumor regression of 75% only. A good accumulation of 1 was observed in the tumor mass. The time course of the body weight attested that cisplatin induced elevated anorexia, whereas treatment with 1 did not induce significant body weight loss throughout the therapeutic experiment. PMID- 28984333 TI - Interlayer bond polarizability model for stacking-dependent low-frequency Raman scattering in layered materials. AB - Two-dimensional (2D) layered materials have been extensively studied owing to their fascinating and technologically relevant properties. Their functionalities can be often tailored by the interlayer stacking pattern. Low-frequency (LF) Raman spectroscopy provides a quick, non-destructive and inexpensive optical technique for stacking characterization, since the intensities of LF interlayer vibrational modes are sensitive to the details of the stacking. A simple and generalized interlayer bond polarizability model is proposed here to explain and predict how the LF Raman intensities depend on complex stacking sequences for any thickness in a broad array of 2D materials, including graphene, MoS2, MoSe2, NbSe2, Bi2Se3, GaSe, h-BN, etc. Additionally, a general strategy is proposed to unify the stacking nomenclature for these 2D materials. Our model reveals the fundamental mechanism of LF Raman response to the stacking, and provides general rules for stacking identification. PMID- 28984334 TI - Cobalt ion-coordinated self-assembly synthesis of nitrogen-doped ordered mesoporous carbon nanosheets for efficiently catalyzing oxygen reduction. AB - The design and synthesis of a promising porous carbon-based electrocatalyst with an ordered and uninterrupted porous structure for oxygen reduction reaction (ORR) is still a significant challenge. Herein, an efficient catalyst based on cobalt embedded nitrogen-doped ordered mesoporous carbon nanosheets (Co/N-OMCNS) is successfully prepared through a two-step procedure (cobalt ion-coordinated self assembly and carbonization process) using 3-aminophenol as a nitrogen source, cobalt acetate as a cobalt source and Pluronic F127 as a mesoporous template. This work indicates that the formation of a two dimensional nanosheet structure is directly related to the extent of the cobalt ion coordination interaction. Moreover, the critical roles of pyrolysis temperature in nitrogen doping and ORR catalytic activity are also investigated. Benefiting from the high surface area and graphitic degree, high contents of graphitic N and pyridinic N, ordered interconnected mesoporous carbon framework, as well as synergetic interaction between the cobalt nanoparticles and protective nitrogen doped graphitic carbon layer, the resultant optimal catalyst Co/N-OMCNS-800 (pyrolyzed at 800 degrees C) exhibits comparable ORR catalytic activity to Pt/C, superior tolerance to methanol crossover and stability. PMID- 28984335 TI - The design of synthetic superoxide dismutase mimetics: seven-coordinate water soluble manganese(ii) and iron(ii) complexes and their superoxide dismutase-like activity studies. AB - Bio-inspired manganese [Mn(N5Py)(H2O)(CH3OH)](ClO4)2 (1) and iron [Fe(N5Py)(H2O)(ClO4)]ClO4 (2) complexes derived from a pentadentate ligand (N5Py = 2,6-bis((E)-1-phenyl-2-(pyridin-2-ylmethylene)hydrazinyl)pyridine) framework containing a N5 binding motif were synthesized and characterized using different spectroscopic methods. The molecular structures of complexes 1 and 2 were determined by X-ray crystallography. These complexes were found to be stable under physiological conditions and exhibited an excellent superoxide dismutase (SOD) activity. The SOD activity was determined by a xanthine-xanthine oxidase nitro blue tetrazolium assay and the IC50 values were determined to be 1.53 and 2.09 MUM, respectively. PMID- 28984336 TI - A Retrospective Evaluation of the Epithelial Changes/Lesions and Neoplasms of the Gallbladder in Turkey and a Review of the Existing Sampling Methods: A Multicentre Study. AB - OBJECTIVE: As there is continuing disagreement among the observers on the differential diagnosis between the epithelial changes/lesions and neoplasms of the gallbladder, this multicentre study was planned in order to assess the rate of the epithelial gallbladder lesions in Turkey and to propose microscopy and macroscopy protocols. MATERIAL AND METHOD: With the participation of 22 institutions around Turkey that were included in the Hepato-Pancreato-Biliary Study Group, 89,324 cholecystectomy specimens sampled from 2003 to 2016 were retrospectively evaluated. The numbers of adenocarcinomas, dysplasias, intracholecystic neoplasms/adenomas, intestinal metaplasias and reactive atypia were identified with the review of pathology reports and the regional and countrywide incidence rates were presented in percentages. RESULTS: Epithelial changes/lesions were reported in 6% of cholecystectomy materials. Of these epithelial lesions, 7% were reported as adenocarcinoma, 0.9% as high-grade dysplasia, 4% as low-grade dysplasia, 7.8% as reactive/regenerative atypia, 1.7% as neoplastic polyp, and 15.6% as intestinal metaplasia. The remaining lesions (63%) primarily included non-neoplastic polypoids/hyperplastic lesions and antral/pyloric metaplasia. There were also differences between pathology laboratories. CONCLUSION: The major causes of the difference in reporting these epithelial changes/lesions and neoplasms include the differences related to the institute's oncological surgery frequency, sampling protocols, geographical dissimilarities, and differences in the diagnoses/interpretations of the pathologists. It seems that the diagnosis may change if new sections are taken from the specimen when any epithelial abnormality is seen during microscopic examination of the cholecystectomy materials. PMID- 28984339 TI - A Unique Immunofluorescence Protocol to Detect Protein Expression in Vascular Tissues: Tacking a Long Standing Pathological Hitch. AB - OBJECTIVE: Autofluorescence induced interference is one of the major drawbacks in immunofluorescence analysis of formalin-fixed paraffin-embedded tissues, as it decreases the signal-to-noise ratio of specific labeling. Apart from aldehyde fixation induced artifacts; collagen and elastin, red blood cells and endogenous fluorescent pigment lipofuscin are prime sources of autofluorescence in vascular and aging tissues. We describe herein, an optimized indirect-immunofluorescence method for archival formalin-fixed paraffin-embedded tissues tissues and cryo sections, using a combination of 3-reagents in a specific order, to achieve optimal fluorescence signals and imaging. MATERIAL AND METHOD: Human telomerase reverse transcriptase, a protein implicated as a proliferation marker, was chosen relevant to its expression in solid tumors along with 3 other intracellular proteins exhibiting nuclear and/or cytoplasmic expression. Staining was performed on 10 glioma tissue sections along with 5 of their cryo sections, 5 sections each of hepatocellular, lung, papillary-thyroid and renal cell carcinoma, with 10 non malignant brain tissue samples serving as control. Specimens were imaged using epifluorescence microscopy, followed by software-based quantification of fluorescence signals for statistical analysis and validation. RESULTS: We observed that the combined application of sodium-borohydride followed by crystal violet before antigen retrieval and a Sudan black B treatment after secondary antibody application proved to be most efficacious for masking autofluorescence/non-specific background in vascular tissues. CONCLUSION: This unique trio-methodology provides quantifiable observations with maximized fluorescence signal intensity of the target protein for longer retention time of the signal even after prolonged storage. The results can be extrapolated to other human tissues for different protein targets. PMID- 28984341 TI - Immunohistochemical Analysis of the Extrinsic Apoptosis Process in the Non Neoplastic and Neoplastic Prostate. AB - OBJECTIVE: Deviations in the apoptotic process have been demonstrated in prostate carcinogenesis. We aimed to evaluate especially the process of extrinsic apoptosis in the spectrum of neoplastic lesions of the prostate epithelium so as to reveal the variations in the apoptotic process. MATERIAL AND METHOD: The study included 20 benign prostatic hyperplasia, 8 high-grade prostatic intraepithelial neoplasia and 82 prostatic carcinoma patients. Immunohistochemistry was performed on sections obtained from materials of suprapubic prostatectomy, tru-cut biopsy, transurethral resection and radical prostatectomy. While Fas and FasL were evaluated in glandular and stromal areas, DcR1 and FLIP were evaluated in only glandular areas. Intensity and extent of immunostaining for Fas and FasL antibodies were separately scored and both scores were summarized. The total score of >= 4 both for Fas and FasL, expressions of FLIP and DcR1determined in more than 5% of glandular areas were accepted as positive. RESULTS: Glandular FasL positivity was observed in 63.8 and 20% of the cases with prostatic carcinoma and benign prostatic hyperplasia, respectively (p=0.001). The loss of stromal Fas expression in PCa was obvious (p < 0.001). FLIP positivity was more frequently seen in high-grade prostatic intraepithelial neoplasia and PCa. CONCLUSION: In prostatic carcinoma, decreased stromal Fas expression, contrary to higher glandular FasL positivity, supports the assertion that sensitivity of epithelial and stromal cells to apoptosis and their protective pathways against apoptosis undergo alterations. Increased FLIP expressions in high-grade prostatic intraepithelial neoplasia and prostatic carcinoma can also be interpreted accordingly. PMID- 28984342 TI - Follicular Dendritic Cell Sarcoma of the Larynx: Apropos a Rare Case with Review of the Literature. AB - Extranodal follicular dendritic cell sarcomas are extremely rare neoplasms included under the hematolymphoid and dendritic group of neoplasms. Histologically, fascicular, whorled spindle cells with sprinkled lymphocytes are typical; however higher grade epithelioid morphology seen in a subset makes diagnosis of follicular dendritic cell sarcoma challenging. Rarity of occurrence, a wide histologic spectrum and a long list of differential diagnostic entities render follicular dendritic cell sarcoma an under-recognized entity susceptible to diagnostic pitfalls. Application of a judicious panel of immunohistochemical markers is imperative to avoid errors in diagnosis and patient management. We report here an extremely rare case of follicular dendritic cell sarcoma of the larynx- a hitherto unreported site. PMID- 28984343 TI - The World Health Organization Classification of Odontogenic Lesions: A Summary of the Changes of the 2017 (4th) Edition. AB - The 4 < sup > th < /sup > edition of the World Health Organization (WHO) Classification of Head and Neck Tumors was published in January 2017. The edition serves to provide an updated classification scheme, and extended genetic and molecular data that are useful as diagnostic tools for the lesions of the head and neck region. This review focuses on the most current update of odontogenic cysts and tumors based on the 2017 WHO edition. The updated classification has some important differences from the 3 < sup > rd < /sup > edition (2005), including a new classification of odontogenic cysts, 'reclassified' odontogenic tumors, and some new entities. PMID- 28984344 TI - Concomitant Intraocular Retinoblastoma and Choroidal Hemangioma in a 1-Year-Old Boy. AB - We report a case of concomitant choroidal hemangioma in an eye that harbored intraocular retinoblastoma (RB) in a 1-year-old child. A 12-month-old boy presented with right white pupil (Leukocoria). The initial clinical diagnosis was unilateral intraocular RB Group C. The eye was treated initially by systemic chemotherapy combined with focal consolidation therapy followed by I-125 plaque radiotherapy. Massive sub-retinal recurrence was seen 4 months later, and Magnetic Resonance Imaging (MRI) showed extra-scleral invasion of the tumor, and therefore enucleation was performed. Microscopic examination revealed a differentiated retinoblastoma associated at the site of the base of the tumor with choroidal hemangioma with trans-scleral invasion. Orbit MRI was repeated 3 months after the surgery, and there was no orbital tumor recurrence. We are reporting a rare case of pathologically concomitant choroidal hemangioma with trans-scleral invasion in an eye that harbored active recurrent intraocular RB. This trans-scleral extension of hemangioma was misinterpreted by MRI as extraocular retinoblastoma and resulted in enucleation. PMID- 28984345 TI - Changes in the Hematopoietic System and Blood Under the Influence of Heavy Metal Salts Can Be Reduced with Vitamin E. AB - OBJECTIVE: The aim of our work was to study the blood parameters and bone marrow morphological changes in rats exposed to increased amounts of heavy metal salts and the effect of vitamin E. MATERIAL AND METHOD: Investigation of bone marrow structural features and blood parameters was performed in sexually mature Wistar male rats (n=84). RESULTS: Exposure to increased amounts of heavy metal salts led to the inhibition of erythropoiesis and leukopoiesis, as well as a synchronized increase in the number of megakaryocytes which was clearly reflected in the blood: the number of erythrocytes, leukocytes and Hb decreased, and the number of platelets increased. These changes in the blood and bone marrow were less pronounced when vitamin E was used as an adjuster. CONCLUSION: When increased amounts of HMS enter the rats' bodies, suppression of erythropoiesis and leukocytopoiesis occurs while thrombocytopoiesis increases. These changes depend on the period of intake of heavy metal salts. The adjustment of vitamin E reduces the severity of the cytotoxic effect of heavy metals and improves readaptation in the recovery period. PMID- 28984346 TI - Do the Well Known Prognostic Parameters in Pancreatic Ductal Adenocarcinoma Really Reflect Survival? AB - OBJECTIVE: Pancreatic ductal adenocarcinoma is an aggressive tumor with short survival. In this study we aimed to investigate the effect of well-known prognostic parameters on survival in these tumors. MATERIAL AND METHOD: A total of 56 pancreatic ductal adenocarcinoma cases diagnosed between 2005 and 2014 were included in the study. Survival data were obtained and histopathological parameters were re-evaluated in each patient. RESULTS: Tumor size (p=0.029), mitotic count (p=0.030), lymph node metastasis (p=0.003), metastatic lymph node ratio (p < 0.001) and ampullary invasion (p=0.044) had a statistically significant relationship with survival. However, there was no relationship between survival and tumor grade, lymphovascular and perineural invasion, and peripancreatic soft tissue invasion. CONCLUSION: Our results showed that existent 2010 WHO pancreatic ductal adenocarcinoma grading parameters excluding mitotic count are subjective and not applicable. Considering that almost all of the tumors in our series were larger than 2 cm, we think that the 2 cm cut-off in tumor size is insufficient to make the tumor stage pT2. Peripancreatic soft tissue invasion, which is a common finding in pancreatic ductal adenocarcinoma, should also not be assessed like adjacent tissue invasion and make the tumor reach pT3 stage independent of tumor size. It is clear that the existent WHO tumor grading and pT staging parameters need to be revised and the mitotic count, which correlates with survival, should be presented in pathology reports. PMID- 28984347 TI - Tumorous Conditions of the Hand: A Retrospective Review of 402 Cases. AB - OBJECTIVE: Knowledge concerning treatment and care of hand lesions is often based on small case series, case reports and a few large general case series. The aim of this study is to present our experience with hand tumors' and tumor-like lesions' incidence, age range and localizations. MATERIAL AND METHOD: Between 2006-2016, 402 patients operated and histopathologically diagnosed with bone and soft tissue tumorous conditions of the hand were evaluated retrospectively. RESULTS: Three hundred sixty one out of 402 cases (89.8%) were soft tissue tumors and 41 cases (10.2%) were osseous tumors of the hand. A total of 10 malignant tumors (2.5%) were encountered in the hand. The average age of the patients was 41.9 years (ranged from 1 to 83 years). Among 361 soft tissue tumors, only 6 cases (1.6%) were malignant and they were squamous cell tumors (n=5) and synovial sarcoma (n=1). The most common soft tissue pathology was ganglion cyst (n=125). The most common bone tumor was enchondroma, diagnosed in 26 patients (6.4% of all patients). Primary malignant bone tumors were extremely rare in the hand; one osteosarcoma and one chondrosarcoma were reported. Metastatic tumors to the hand were seen in two patients; and they were lung carcinoma and chondrosarcoma metastasis. CONCLUSION: Up-date knowledge and a thorough understanding of the nature and demographic characteristics of the tumorous conditions of the hand are crucial for accurate diagnosis and appropriate treatment. PMID- 28984348 TI - Acute Myeloid Leukaemia with Gene Mutation: A Correlation with Haematological and Immunophenotypic Characteristics and Our Experience in a Tertiary Care Cancer Center in South India. AB - OBJECTIVE: Molecular genetic analysis of FLT3, NPM1, and CEBPA is already the standard of care in patients with acute myeloid leukaemia (AML) and represents the most frequent genetic alterations and important diagnostic and prognostic indicators. This study was undertaken to determine the frequency of FLT3 and NPM1 gene mutations in our institution and to characterize the association between gene mutations and haematological parameters as well as immunophenotypic features. MATERIAL AND METHOD: Morphological, haematological and immunophenotypic characteristics of NPM1 and FLT3 mutations in 126 patients of de novo AML including adults and children were studied. Apart from the French American British (FAB) method for classification, blasts were assessed for cuplike morphology as per strict definition for cuplike nuclei, >=10% blasts with nuclear invaginations >=25% of the nuclear area. RESULTS: FLT3 mutation in 31/126 (25%) and NPM1 mutation was found in 17/126 (13.4%) of the AML patients. 6 (5%) samples were positive for both NPM1 and FLT3/ITD mutations. Associations between the FLT3 and NPM1 gene mutations with haematological and immunophenotypic characteristics are reported. CONCLUSION: The results suggest that presence of distinct morphology and haematological and immunophenotypic characteristics together may serve as important indicators and surrogate for NPM1 and FLT3/ITD mutations. Further, comprehensive studies on the biological effects of NPM1 and FLT3/ITD mutations and their interactions with other genetic alterations are needed to gain insight into the molecular mechanism of these mutations involved in the pathogenesis of AML. PMID- 28984349 TI - Quality of life and comorbidities associated with Dravet syndrome severity: a multinational cohort survey. AB - AIM: To test the hypothesis that higher seizure burden in Dravet syndrome is associated with increased comorbidities and lower quality of life (QoL) in a large cohort of patients with Dravet syndrome and their caregivers in Europe. METHOD: An extensive survey of caregivers of patients with Dravet syndrome on experiences of diagnosis, seizure burden, management, social and financial impact, and health services use was administered online in 10 languages. RESULTS: The survey received 584 unique responses from caregivers of paediatric (83%) and adult (17%) patients with Dravet syndrome (aged <1-48y). Despite broadly following current treatment guidance, less than 10% of patients were seizure free in the previous 3 months. Nearly all (99.6%) patients aged 5 years or older experienced at least one or more motor, speech, learning, or behavioural impairment. High seizure frequency was related to more reports of emergency treatment, comorbidities, and a lower QoL (as measured by the standardized instrument EQ-5D-5L). If not diagnosed at the first instance, the majority (83%) of adults, but less than 20% of 6- to 11-year-olds were diagnosed after 4 or more years. INTERPRETATION: Patients with Dravet syndrome with the highest current seizure frequency suffer from more comorbidities and have a lower QoL. Therefore, more effective antiepileptic treatments are needed. WHAT THIS PAPER ADDS: The survey captured about 15% of all patients with Dravet syndrome in Europe. Less than 10% of patients had current seizure freedom. Patients with a high current seizure burden have more comorbidities and lower quality of life. PMID- 28984350 TI - Thinking or feeling? An exploratory study of maternal scaffolding, child mental state talk, and emotion understanding in language-impaired and typically developing school-aged children. AB - BACKGROUND: Mother-child mental state talk (MST) supports children's developing social-emotional understanding. In typically developing (TD) children, family conversations about emotion, cognition, and causes have been linked to children's emotion understanding. Specific language impairment (SLI) may compromise developing emotion understanding and adjustment. AIMS: We investigated emotion understanding in children with SLI and TD, in relation to mother-child conversation. Specifically, is cognitive, emotion, or causal MST more important for child emotion understanding and how might maternal scaffolding support this? SAMPLE: Nine 5- to 9-year-old children with SLI and nine age-matched typically developing (TD) children, and their mothers. METHOD: We assessed children's language, emotion understanding and reported behavioural adjustment. Mother-child conversations were coded for MST, including emotion, cognition, and causal talk, and for scaffolding of causal talk. RESULTS: Children with SLI scored lower than TD children on emotion understanding and adjustment. Mothers in each group provided similar amounts of cognitive, emotion, and causal talk, but SLI children used proportionally less cognitive and causal talk than TD children did, and more such child talk predicted better child emotion understanding. Child emotion talk did not differ between groups and did not predict emotion understanding. Both groups participated in maternal-scaffolded causal talk, but causal talk about emotion was more frequent in TD children, and such talk predicted higher emotion understanding. CONCLUSIONS: Cognitive and causal language scaffolded by mothers provides tools for articulating increasingly complex ideas about emotion, predicting children's emotion understanding. Our study provides a robust method for studying scaffolding processes for understanding causes of emotion. PMID- 28984351 TI - Scaling Theory of Mind in a Small-Scale Society: A Case Study From Vanuatu. AB - Although theory of mind (ToM) is argued to emerge between 3 and 5 years of age, data from non-Western, small-scale societies suggest diversity. Deeper investigations into these settings are warranted. In the current study, over 400 Melanesian children from Vanuatu (range = 3-14 years), growing up in either urban or rural remote environments, completed culturally tailored ToM batteries. Results show a marked delay in false belief (FB) performance, particularly among participants from rural villages. By further investigating a diverse range of concepts beyond FB, we illustrate two unique cultural sequences for a suite of mental state concepts among urban and rural ni-Vanuatu children. Implications for social and cultural influences on the development of ToM are discussed. PMID- 28984352 TI - Development of the Hand Assessment for Infants: evidence of internal scale validity. AB - AIM: The aim of this study was to develop a descriptive and evaluative assessment of upper limb function for infants aged 3 to 12 months and to investigate its internal scale validity for use with infants at risk of unilateral cerebral palsy. METHOD: The concepts of the test items and scoring criteria were developed. Internal scale validity and aspects of reliability were investigated on the basis of 156 assessments of infants at 3 to 12 months corrected age (mean 7.2mo, SD 2.5) with signs of asymmetric hand use. Rasch measurement model analysis and non-parametric statistics were used. RESULTS: The new test, the Hand Assessment for Infants (HAI), consists of 12 unimanual and five bimanual items, each scored on a 3-point rating scale. It demonstrated a unidimensional construct and good fit to the Rasch model requirements. The excellent person reliability enabled person separation to six significant ability strata. The HAI produced an interval-level measure of bilateral hand use as well as unimanual scores of each hand, allowing a quantification of possible asymmetry expressed as an asymmetry index. INTERPRETATION: The HAI can be considered a valid assessment tool for measuring bilateral hand use and quantifying side difference between hands among infants at risk of developing unilateral cerebral palsy. WHAT THIS PAPER ADDS: The Hand Assessment for Infants (HAI) measures the use of both hands and quantifies a possible asymmetry of hand use. HAI is valid for infants at 3 to 12 months corrected age at risk of unilateral cerebral palsy. PMID- 28984353 TI - Care maps for children with medical complexity. AB - AIM: Children with medical complexity require multiple providers and services to keep them well and at home. A care map is a patient/family-created diagram that pictorially maps out this complex web of services. This study explored what care maps mean for families and healthcare providers to inform potential for clinical use. METHOD: Parents (n=15) created care maps (hand drawn n=10 and computer generated n=5) and participated in semi-structured interviews about the process of developing care maps and their perceived impact. Healthcare providers (n=30) reviewed the parent-created care maps and participated in semi-structured interviews. Data were analysed for themes and emerging theory using a grounded theory analytical approach. RESULTS: Data analysis revealed 13 overarching themes that were further categorized into three domains: features (characteristics of care maps), functions (what care maps do), and emerging outcomes (benefits of care map use). These domains further informed a definition and a theoretical model of how care maps work. INTERPRETATION: Our findings suggest that care maps may be a way of supporting patient- and family-centred care by graphically identifying and integrating experiences of the family as well as priorities for moving forward. WHAT THIS PAPER ADDS: Care maps were endorsed as a useful tool by families and providers. They help healthcare providers better understand parental priorities for care. Parents can create care maps to demonstrate the complex burden of care. They are a unique visual way to incorporate narrative medicine into practice. PMID- 28984354 TI - CPD of the future: a partnership between quality improvement and competency-based education. AB - CONTEXT: Many of those involved in continuing professional development (CPD) over the past 10 years have engaged in discussions about its goals and activities. Whereas in the past CPD was viewed as an education intervention directed towards the medical expert role, recent research highlights the need to expand the scope of CPD and to promote its more explicit role in improving patient care and health outcomes. Recent developments in quality improvement (QI) and competency-based medical education (CBME), guided by appropriate theories of learning and change, can shed light on how the field might best advance. This paper describes principles of QI and CBME and how they might contribute to CPD, explores theoretical perspectives that inform such an integration and suggests a future model of CPD. DISCUSSION: Continuing professional development seeks to improve patient outcomes by increasing physician knowledge and skills and changing behaviours, whereas QI takes the approach of system and process change. Combining the strengths of a CPD approach with strategies known to be effective from the field of QI has the potential to harmonise the contributions of each, and thereby to lead to better patient outcomes. Similarly, competency-based CPD is envisioned to place health needs and patient outcomes at the centre of a CPD system that will be guided by a set of competencies to enhance the quality of practice and the safety of the health system. CONCLUSIONS: We propose that the future CPD system should adhere to the following principles: it should be grounded in the everyday workplace, integrated into the health care system, oriented to patient outcomes, guided by multiple sources of performance and outcome data, and team based; it should employ the principles and strategies of QI, and should be taken on as a collective responsibility by physicians, CPD provider organisations, regulators and the health system. PMID- 28984355 TI - Incidental Findings and Normal Anatomical Variants on Brain MRI in Children for Primary Headaches. AB - When MRI scans of the brain are obtained for evaluation of primary headaches in children, incidental findings and anatomical variants are commonly present. After a review of the prevalence, 11 types are presented. PMID- 28984356 TI - A Real-World Analysis of Migraine: A Cross-Sectional Study of Disease Burden and Treatment Patterns. AB - OBJECTIVE: The purpose of this cross-sectional study was to assess the sociodemographics, disease burden, and treatment patterns of patients with episodic and chronic migraine in the United States. BACKGROUND: Migraine is a disabling neurological disease that places an enormous burden on patients. METHODS: Data were drawn from the Adelphi Migraine United States Disease Specific Programme (index period: January to March 2014). Physicians (N = 150) completed a patient report form on 10 consulting patients with migraine. Episodic migraineurs had <=14 headache days per month (HDM) and those with chronic migraine had >=15. Headache-related disability was assessed with the Migraine Disability Assessment (MIDAS) questionnaire. Disability was also compared across subgroups based on the number of HDM (<=3, 4-7, 8-14, and >=15). RESULTS: A total of 1487 patient report forms were completed. Over 70% of the patients were female, 90.8% (n = 1350) were episodic migraineurs, and 9.2% (n = 137) were chronic migraineurs. Acute treatment was prescribed for >90% of the patients, and >50% had a current prescription for preventive treatment. Despite taking acute and/or preventive treatment, 29.2% of episodic migraineurs (including some patients with <=3 headache days/month) and 73.2% of chronic migraineurs had moderate-to-severe headache-related disability (MIDAS total score >=11). Preventive treatment was discontinued/switched at least once by 26.4% of episodic migraineurs and by 53.3% of chronic migraineurs. Of those patients (n = 382) who gave collective reasons for discontinuation/switching preventive treatment, over 70% selected lack of efficacy and tolerability/safety. CONCLUSIONS: This real-world analysis provides additional support for the unmet medical need for efficacious therapies that reduce migraine frequency and severity, headache-related disability, and have better tolerability for patients with migraine. In addition, further research is needed to better understand the burden of illness among patients with lower migraine frequency, and to implement treatment strategies to prevent progression of the disease. PMID- 28984357 TI - Endocytosis: another pathway in receptor-Gq-TASK signalling. PMID- 28984358 TI - The significance of glutathione and ascorbate in modulating the retrograde high light response in Arabidopsis thaliana leaves. AB - Retrograde signals from the chloroplast control expression of nuclear genes. A large fraction of these genes is affected rapidly upon light intensity shifts. This study was designed to address the interdependence of signaling pathways involved in the rapid high light response and redox and reactive oxygen species signaling by exploiting the glutathione and ascorbate deficient mutants pad2 and vtc1. In the first set of experiments the transcriptional response of the two transcription factors ERF6 and ERF105 that had previously been shown to rapidly respond to light was shown to be deregulated in the pad2 mutant but not in the vtc1 background. The transcriptional response after combining the low-to-high light transfer with methylviologen pretreatment further demonstrated the significance of glutathione in strongly modulating the retrograde response. Transcripts encoding small heat shock proteins (HSP17.4, HSP176a, HSP20-like1 and HSP20-like2) and the lipid transfer protein LTP3 were taken as markers responding to the combinatorial treatment in wild type, and most strongly in pad2 in high light or upon methylviologen treatment. A correlation with H2 O2 accumulation was not observed. It is concluded that glutathione-dependent processes participate in light-triggered rapid gene regulation independent on cellular H2 O2 . PMID- 28984360 TI - Daytime depression in temperature-normalised stem CO2 efflux in young poplar trees is dominated by low turgor pressure rather than by internal transport of respired CO2. AB - Daytime decreases in temperature-normalised stem CO2 efflux (EA_D ) are commonly ascribed to internal transport of respired CO2 (FT ) or to an attenuated respiratory activity due to lowered turgor pressure. The two are difficult to separate as they are simultaneously driven by sap flow dynamics. To achieve combined gradients in turgor pressure and FT , sap flow rates in poplar trees were manipulated through severe defoliation, severe drought, moderate defoliation and moderate drought. Turgor pressure was mechanistically modelled using measurements of sap flow, stem diameter variation, and soil and stem water potential. A mass balance approach considering internal and external CO2 fluxes was applied to estimate FT . Under well-watered control conditions, both turgor pressure and sap flow, as a proxy of FT , were reliable predictors of EA_D . After tree manipulation, only turgor pressure was a robust predictor of EA_D . Moreover, FT accounted for < 15% of EA_D . Our results suggest that daytime reductions in turgor pressure and associated constrained growth are the main cause of EA_D in young poplar trees. Turgor pressure is determined by both carbohydrate supply and water availability, and should be considered to improve our widely used but inaccurate temperature-based predictions of woody tissue respiration in global models. PMID- 28984361 TI - Contrast-enhanced ultrasound examination of the gallbladder and bile ducts: A pictorial essay. AB - The gallbladder and bile ducts are usually assessed initially with conventional gray-scale ultrasound (US). Contrast enhanced US (CEUS) is used when a diagnosis cannot be reached with conventional US. CEUS is easy to learn and perform. US contrast agents can be safely administered in patients with renal function impairment. In this pictorial essay the physics, examination technique and indications of CEUS for examining the gallbladder and bile ducts are reviewed. Gallbladder indications include elucidating normal variants, differentiating sludge from neoplastic lesions, benign and malignant pathology, infection, wall rupture and hemobilia. In the biliary tree CEUS is used for studying benign and malignant tumors, including metastases and cholangiocarcinoma, as well as intrabiliary injection. PMID- 28984362 TI - A unique subphenotype of myasthenia gravis. AB - While extraocular muscles (EOMs) are affected early in generalized myasthenia gravis (MG), and their treatment responsiveness is similar to nonocular muscles, we have identified an ophthalmoplegic (OP) subphenotype that remains resistant to treatment. This subphenotype of ophthalmoplegic MG (OP-MG) most commonly affects acetylcholine receptor antibody-positive cases with juvenile-onset MG and African genetic ancestry. However, a few OP-MG cases have been found with MuSK antibodies and triple-seronegative MG. In a proportion of OP-MG cases, the EOM treatment resistance manifests from treatment initiation, while in others the EOMs may initially respond until a critical trigger, such as treatment interruption or crisis. The management of OP-MG is an unmet need. Managing the visual disability may require a surgical or nonsurgical solution. The ideal case selection for surgery and the timing of surgery should be carefully considered. The pathogenesis of OP-MG remains unknown. A genetic study, using extended whole exome sequencing and an "extreme" phenotype sample of OP-MG versus control MG cases differing only by their EOM responsivity to therapy, discovered several potentially functional OP-MG risk variants. These variants implicate myogenesis and gangliosphingolipid biosynthesis pathways at the EOM endplates in OP-MG. PMID- 28984359 TI - Strategies to retain properties of bone marrow-derived mesenchymal stem cells ex vivo. AB - Mesenchymal stem cells (MSCs) have been extensively used for cell therapies and tissue engineering. The current MSC strategy requires a large quantity of cells for such applications, which can be achieved through cell expansion in culture. In the body, stem cell fate is largely determined by their microenvironment, known as the niche. The complex and dynamic stem cell niche provides physical, mechanical, and chemical cues to collaboratively regulate cell activities. It remains a great challenge to maintain the properties of MSCs in culture. Constructing a microenvironment as an engineered stem cell niche in culture to maintain MSC phenotypes, properties, and functions is a viable strategy to address the issue. Here, we review the current understanding of MSC behavior in the bone marrow niche, describe different strategies to engineer an in vitro microenvironment for maintaining MSC properties and functions, and discuss previous findings on environmental factors critical to the modulation of MSC activities in engineered microenvironments. PMID- 28984363 TI - Evolutionary ecology of telomeres: a review. AB - Telomere-induced selection could take place if telomere-associated disease risk shortens reproductive life span and differently reduces relative fitness among individuals. Some of these diseases first appear before reproductive senescence and could thus influence ongoing selection. We ask whether we can estimate the components of the breeder's equation for telomeres, in which the response to selection (R, by definition "evolution") is the product of ongoing selection (S) and heritability (h2 ). However, telomere inheritance is a conundrum: in quantitative genetics, traits can usually be allocated to categories with relatively high or low heritability, depending on their association with relative fitness. Telomere traits, however, show wide variation in heritability from zero to one, across taxa, gender, ethnicity, age, and disease status. In spite of this, there is divergence in telomere length among populations, supporting past and ongoing telomere evolution. Rates of telomere attrition and elongation vary among taxa with some, but not complete, taxonomic coherence. For example, telomerase is commonly referred to as "restricted to the germ line in mammals," but inbred mice and beavers have telomerase upregulation in somatic tissue, as do many ectotherms. These observations provoke a simplistic understanding of telomere evolutionary biology-clearly much is yet to be discovered. PMID- 28984365 TI - Hydrogen peroxide treatment modulates the transcription of sex-related genes in the sea lice Caligus rogercresseyi. PMID- 28984364 TI - Isolation and analysis of a stromule-overproducing Arabidopsis mutant suggest the role of PARC6 in plastid morphology maintenance in the leaf epidermis. AB - Stromules, or stroma-filled tubules, are thin extensions of the plastid envelope membrane that are most frequently observed in undifferentiated or non-mesophyll cells. The formation of stromules is developmentally regulated and responsive to biotic and abiotic stress; however, the physiological roles and molecular mechanisms of the stromule formation remain enigmatic. Accordingly, we attempted to obtain Arabidopsis thaliana mutants with aberrant stromule biogenesis in the leaf epidermis. Here, we characterize one of the obtained mutants. Plastids in the leaf epidermis of this mutant were giant and pleomorphic, typically having one or more constrictions that indicated arrested plastid division, and usually possessed one or more extremely long stromules, which indicated the deregulation of stromule formation. Genetic mapping, whole-genome resequencing-aided exome analysis, and gene complementation identified PARC6/CDP1/ARC6H, which encodes a vascular plant-specific, chloroplast division site-positioning factor, as the causal gene for the stromule phenotype. Yeast two-hybrid assay and double mutant analysis also identified a possible interaction between PARC6 and MinD1, another known chloroplast division site-positioning factor, during the morphogenesis of leaf epidermal plastids. To the best of our knowledge, PARC6 is the only known A. thaliana chloroplast division factor whose mutations more extensively affect the morphology of plastids in non-mesophyll tissue than in mesophyll tissue. Therefore, the present study demonstrates that PARC6 plays a pivotal role in the morphology maintenance and stromule regulation of non-mesophyll plastids. PMID- 28984366 TI - Metabolism within the specialized guard cells of plants. AB - Contents 1018 I. 1018 II. 1019 III. 1022 IV. 1025 V. 1026 VI. 1029 1030 References 1030 SUMMARY: Stomata are leaf epidermal structures consisting of two guard cells surrounding a pore. Changes in the aperture of this pore regulate plant water-use efficiency, defined as gain of C by photosynthesis per leaf water transpired. Stomatal aperture is actively regulated by reversible changes in guard cell osmolyte content. Despite the fact that guard cells can photosynthesize on their own, the accumulation of mesophyll-derived metabolites can seemingly act as signals which contribute to the regulation of stomatal movement. It has been shown that malate can act as a signalling molecule and a counter-ion of potassium, a well-established osmolyte that accumulates in the vacuole of guard cells during stomatal opening. By contrast, their efflux from guard cells is an important mechanism during stomatal closure. It has been hypothesized that the breakdown of starch, sucrose and lipids is an important mechanism during stomatal opening, which may be related to ATP production through glycolysis and mitochondrial metabolism, and/or accumulation of osmolytes such as sugars and malate. However, experimental evidence supporting this theory is lacking. Here we highlight the particularities of guard cell metabolism and discuss this in the context of the guard cells themselves and their interaction with the mesophyll cells. PMID- 28984367 TI - Host-microbiota interplay in mediating immune disorders. AB - To maintain health, the immune system must maintain a delicate balance between eliminating invading pathogens and avoiding immune disorders such as autoimmunity and allergies. The gut microbiota provide essential health benefits to the host, particularly by regulating immune homeostasis. Dysbiosis, an alteration and imbalance of the gut microbiota, is associated with the development of several autoimmune diseases in both mice and humans. In this review, we discuss recent advances in understanding how certain factors, such as age and gender, affect the gut microbiota, which in turn can influence the development of autoimmune diseases. The age factor in microbiota-dependent immune disorders indicates a window of opportunity for future diagnostic and therapeutic approaches. We also discuss unique commensal bacteria with strong immunomodulatory activity. Finally, we provide an overview of the potential molecular mechanisms whereby gut microbiota induce autoimmunity, as well as the evidence that gut microbiota trigger extraintestinal diseases by inducing the migration of gut-derived immune cells. Elucidating the interaction of gut microbiota and the host immune system will help us understand the pathogenesis of immune disorders, and provide us with new foundations to develop novel immuno- or microbe-targeted therapies. PMID- 28984368 TI - Autogenic drainage for airway clearance in cystic fibrosis. AB - BACKGROUND: Autogenic drainage is an airway clearance technique that was developed by Jean Chevaillier in 1967. The technique is characterised by breathing control using expiratory airflow to mobilise secretions from smaller to larger airways. Secretions are cleared independently by adjusting the depth and speed of respiration in a sequence of controlled breathing techniques during exhalation. The technique requires training, concentration and effort from the individual. It is important to systematically review the evidence demonstrating that autogenic drainage is an effective intervention for people with cystic fibrosis. OBJECTIVES: To compare the clinical effectiveness of autogenic drainage in people with cystic fibrosis with other physiotherapy airway clearance techniques. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews, as well as two trials registers (31 August 2017).Dtae of most recent search of the Cochrane Cystic Fibrosis Trials Register: 25 September 2017. SELECTION CRITERIA: We identified randomised and quasi randomised controlled studies comparing autogenic drainage to another airway clearance technique or no therapy in people with cystic fibrosis for at least two treatment sessions. DATA COLLECTION AND ANALYSIS: Data extraction and assessments of risk of bias were independently performed by two authors. The authors assessed the quality of the evidence using the GRADE system. The authors contacted two investigators for further information pertinent to their published studies. MAIN RESULTS: Searches retrieved 35 references to 21 individual studies, of which seven (n = 208) were eligible for inclusion. One study was of parallel design with the remaining six being cross-over in design; participant numbers ranged from 17 to 75. The total study duration varied between four days and two years. The age of participants ranged between seven and 63 years with a wide range of disease severity reported. Six studies enrolled participants who were clinically stable, whilst participants in one study had been hospitalised with an infective exacerbation. All studies compared autogenic drainage to one (or more) other recognised airway clearance technique. Exercise is commonly used as an alternative therapy by people with cystic fibrosis; however, there were no studies identified comparing exercise with autogenic drainage.The quality of the evidence was generally low or very low. The main reasons for downgrading the level of evidence were the frequent use of a cross-over design, outcome reporting bias and the inability to blind participants.The review's primary outcome, forced expiratory volume in one second, was the most common outcome measured and was reported by all seven studies; only three studies reported on quality of life (also a primary outcome of the review). One study reported on adverse events and described a decrease in oxygen saturation levels whilst performing active cycle of breathing techniques, but not with autogenic drainage. Six of the seven included studies measured forced vital capacity and three of the studies used mid peak expiratory flow (per cent predicted) as an outcome. Six studies reported sputum weight. Less commonly used outcomes included oxygen saturation levels, personal preference, hospital admissions or intravenous antibiotics. There were no statistically significant differences found between any of the techniques used with respect to the outcomes measured except when autogenic drainage was described as being the preferred technique of the participants in one study over postural drainage and percussion. AUTHORS' CONCLUSIONS: Autogenic drainage is a challenging technique that requires commitment from the individual. As such, this intervention merits systematic review to ensure its effectiveness for people with cystic fibrosis. From the studies assessed, autogenic drainage was not found to be superior to any other form of airway clearance technique. Larger studies are required to better evaluate autogenic drainage in comparison to other airway clearance techniques in view of the relatively small number of participants in this review and the complex study designs. The studies recruited a range of participants and were not powered to assess non-inferiority. The varied length and design of the studies made the analysis of pooled data challenging. PMID- 28984370 TI - A practical approach to estimate diffusional leakages of leaf chamber of open gas exchange systems using intact leaves. AB - We propose a novel approach to determine the coefficient of CO2 diffusional leakage (k_CO2 ) in the chamber of a portable open gas exchange system (Li-6400, Li-Cor Inc., NE, USA) using intact leaves. Assuming that dark respiration rate (Rn ) is constant at various CO2 concentrations, at least in a short term, k_CO2 should be the value that makes the leak-corrected Rn constant. We used 2 representative tree species native to northern Japan, Japanese white birch (Betula platyphylla var. japonica) and Japanese oak (Quercus mongolica var. crispula), to determine k_CO2 , by measuring Rn at various CO2 concentrations. Irrespective of the species, k_CO2 estimated by the present approach was well correlated with the diffusional leak coefficient (k_flow ) estimated by the generally used approach that utilizes CO2 concentrations inside and outside the chamber based on thermally killed leaves at various flow rates. Furthermore, the present approach does not require the ambient CO2 concentration outside the chamber (Ca ) if Ca in the laboratory is stable, which provides a feasible way to correct the photosynthetic rate, taking diffusional leakage into account. PMID- 28984369 TI - Maternal Multivitamin Intake, Plasma Folate and Vitamin B12 Levels and Autism Spectrum Disorder Risk in Offspring. AB - BACKGROUND: To examine the prospective association between multivitamin supplementation during pregnancy and biomarker measures of maternal plasma folate and vitamin B12 levels at birth and child's Autism Spectrum Disorder (ASD) risk. METHODS: This report included 1257 mother-child pairs, who were recruited at birth and prospectively followed through childhood at the Boston Medical Center. ASD was defined from diagnostic codes in electronic medical records. Maternal multivitamin supplementation was assessed via questionnaire interview; maternal plasma folate and B12 were measured from samples taken 2-3 days after birth. RESULTS: Moderate (3-5 times/week) self-reported supplementation during pregnancy was associated with decreased risk of ASD, consistent with previous findings. Using this as the reference group, low (<=2 times/week) and high (>5 times/week) supplementation was associated with increased risk of ASD. Very high levels of maternal plasma folate at birth (>=60.3 nmol/L) had 2.5 times increased risk of ASD [95% confidence interval (CI) 1.3, 4.6] compared to folate levels in the middle 80th percentile, after adjusting for covariates including MTHFR genotype. Similarly, very high B12 (>=536.8 pmol/L) showed 2.5 times increased risk (95% CI 1.4, 4.5). CONCLUSION: There was a 'U shaped' relationship between maternal multivitamin supplementation frequency and ASD risk. Extremely high maternal plasma folate and B12 levels at birth were associated with ASD risk. This hypothesis-generating study does not question the importance of consuming adequate folic acid and vitamin B12 during pregnancy; rather, raises new questions about the impact of extremely elevated levels of plasma folate and B12 exposure in-utero on early brain development. PMID- 28984371 TI - Sonographic diagnosis and prognosis of fetal arachnoid cysts. AB - PURPOSE: To explore the clinical significance of sonographic (US) diagnosis of fetal arachnoid cysts and to evaluate their prognosis. METHODS: Sixty fetuses deemed to have arachnoid cysts by prenatal US were included in this study. Data from serial US, prenatal and/or postnatal MRI, or post-mortem examinations were retrospectively analyzed. For live births, the developmental quotient scores were determined using the Gesell Developmental Scale. RESULTS: Thirty fetuses were diagnosed during the second trimester and another 30 fetuses were diagnosed in the third trimester. Fifty-one lesions were located in the supratentorial compartment, and 9 were located in the posterior fossa. Twenty-four lesions were isolated, and the remaining lesions were associated with intracranial and/or extra central nervous system malformations. The evolution of the cysts included progression, stability, or spontaneous resolution. The outcomes included induced abortion, intrauterine death, live birth with either normal neurodevelopment or mental retardation, and infant mortality. Two cases were lost to follow-up. The accuracy of prenatal US diagnosis was 86.2% (50/58). CONCLUSION: Prenatal US is the modality of choice for the diagnosis of fetal arachnoid cysts. Serial US examinations are critical to monitor the lesions. Moreover, prenatal MRI is a valuable complementary tool. For live births, the prognosis appears to be good. PMID- 28984372 TI - Adverse Maternal and Birth Outcomes in Women Admitted to Hospital for Hyperemesis Gravidarum: a Population-Based Cohort Study. AB - BACKGROUND: Evidence for risks of adverse maternal and birth outcomes in women with hyperemesis gravidarum (HG) is predominantly from small studies, unknown, or conflicting. METHODS: A population-based cohort study using secondary health care records (Hospital Episode Statistics covering all of England from 1997 to 2012) was used to calculate odds ratios (OR) with 99% confidence intervals (CI) for the association between HG hospital admission and adverse outcomes, adjusting for maternal and pregnancy confounders. RESULTS: Within 8 211 850 pregnancies ending in live births or stillbirths, women with HG had increased odds of anaemia (OR 1.28, 99% CI 1.23, 1.33), preeclampsia (OR 1.16, 99% CI 1.09, 1.22), eclampsia (OR 1.84, 99% CI 1.07, 3.18), venous thromboembolism antenatally (OR 1.94, 99% CI 1.57, 2.39 for deep vein thrombosis, and OR 2.54, 99% CI 1.89, 3.40 for pulmonary embolism) and post-partum. Odds of stillbirth (OR 0.77, 99% CI 0.66, 0.89) and post-term (OR 0.86, 99% CI 0.81, 0.92) delivery were decreased. Women were more likely to be induced (OR 1.20, 99% CI 1.16, 1.23), to deliver preterm (OR 1.11, 99% CI 1.05, 1.17), very preterm (OR 1.18, 99% CI 1.05, 1.32), or by caesarean section (OR 1.12, 99% CI 1.08, 1.16), to have low birthweight (OR 1.12, 99% CI 1.08, 1.17) or small for gestational age (OR 1.06, 99% CI 1.01, 1.11) babies and although absolute risks were small, their offspring were more likely to undergo resuscitation or neonatal intensive care. CONCLUSION: HG may have important antenatal and postnatal consequences that should be considered in communications between health care professionals and women to best manage HG and prevent progression during pregnancy. PMID- 28984373 TI - Pulmonary ultrasound scoring system for intubated critically ill patients and its association with clinical metrics and mortality: A prospective cohort study. AB - PURPOSE: Pulmonary ultrasound (PU) examination at the point-of-care can rapidly identify the etiology of acute respiratory failure (ARF) and assess treatment response. The often-subjective classification of PU abnormalities makes it difficult to document change over time and communicate findings across providers. The study goal was to develop a simple, PU scoring system that would allow for standardized documentation, have high interprovider agreement, and correlate with clinical metrics. METHODS: In this prospective study of 250 adults intubated for ARF, a PU examination was performed at intubation, 48-hours later, and at extubation. A total lung score (TLS) was calculated. Clinical metrics and final diagnosis were extracted from the medical record. RESULTS: TLS correlated positively with mortality (P = .03), ventilator hours (P = .003), intensive care unit, and hospital length of stay (P = .003, P = .008), and decreasing PaO2 /FiO2 (P < .001). Agreement of PU findings was very good (kappa = 0.83). Baseline TLS and subscores differed significantly between ARF categories (nonpulmonary, obstructive, and parenchymal disease). CONCLUSIONS: A quick, scored, PU examination was associated with clinical metrics, including mortality among a diverse population of patients intubated for ARF. In addition to diagnostic and prognostic information at the bedside, a standardized and quantifiable approach to PU provides objectivity in serial assessment and may enhance communication of findings between providers. PMID- 28984375 TI - Context matters when striving to promote active and lifelong learning in medical education. AB - : WHERE DO WE STAND NOW?: In the 30 years that have passed since The Edinburgh Declaration on Medical Education, we have made tremendous progress in research on fostering 'self-directed and independent study' as propagated in this declaration, of which one prime example is research carried out on problem-based learning. However, a large portion of medical education happens outside of classrooms, in authentic clinical contexts. Therefore, this article discusses recent developments in research regarding fostering active learning in clinical contexts. SELF-REGULATED, LIFELONG LEARNING IN MEDICAL EDUCATION: Clinical contexts are much more complex and flexible than classrooms, and therefore require a modified approach when fostering active learning. Recent efforts have been increasingly focused on understanding the more complex subject of supporting active learning in clinical contexts. One way of doing this is by using theory regarding self-regulated learning (SRL), as well as situated learning, workplace affordances, self-determination theory and achievement goal theory. Combining these different perspectives provides a holistic view of active learning in clinical contexts. ENTRY TO PRACTICE, VOCATIONAL TRAINING AND CONTINUING PROFESSIONAL DEVELOPMENT: Research on SRL in clinical contexts has mostly focused on the undergraduate setting, showing that active learning in clinical contexts requires not only proficiency in metacognition and SRL, but also in reactive, opportunistic learning. These studies have also made us aware of the large influence one's social environment has on SRL, the importance of professional relationships for learners, and the role of identity development in learning in clinical contexts. Additionally, research regarding postgraduate lifelong learning also highlights the importance of learners interacting about learning in clinical contexts, as well as the difficulties that clinical contexts may pose for lifelong learning. However, stimulating self-regulated learning in undergraduate medical education may also make postgraduate lifelong learning easier for learners in clinical contexts. PMID- 28984374 TI - Lessons learned from 15 years of non-grades-based selection for medical school. AB - CONTEXT: Thirty years ago, it was suggested in the Edinburgh Declaration that medical school applicants should be selected not only on academic, but also on non-academic, attributes. The main rationale behind extending medical school selection procedures with the evaluation of (non-academic) personal qualities is that this will lead to the selection of students who will perform better as a doctor than those who are selected on the basis of academic measures only. A second rationale is the expectation that this will lead to a representative health workforce as a result of reduced adverse impact. The aims of this paper are (i) to describe what can be learned about the use of selection criteria other than grades from over 15 years of Dutch experience and (ii) to summarise current knowledge on the issue of adverse impact in relation to non-grades-based selection. METHODS: A narrative review was undertaken of the (published) evidence that has resulted from non-grades-based school-specific selection procedures in the Netherlands and from recent explorations of the effect of the use of non grades-based selection criteria on student diversity. RESULTS: The Dutch evidence is grouped into five key themes: the effect of participation in voluntary selection procedures, the assessment of pre-university extracurricular activities, the use of work samples, Dutch experiences with situational judgement tests and the effects of changing circumstances. This is followed by several lessons learned for medical schools that aim to increase their student diversity. CONCLUSION: Over the last 30 years, important steps towards reliable and valid methods for measuring non-academic abilities have been taken. The current paper describes several lessons that can be learned from the steps taken in the Dutch context. The importance of sharing evidence gathered around the globe and building on this evidence to reach our goal of predicting who will be a good doctor is acknowledged. PMID- 28984376 TI - Applying adverse outcome pathways and species sensitivity-weighted distribution to predicted-no-effect concentration derivation and quantitative ecological risk assessment for bisphenol A and 4-nonylphenol in aquatic environments: A case study on Tianjin City, China. AB - Adverse outcome pathways (AOPs) are a novel concept that effectively considers the toxic modes of action and guides the ecological risk assessment of chemicals. To better use toxicity data including biochemical or molecular responses and mechanistic data, we further developed a species sensitivity-weighted distribution (SSWD) method for bisphenol A and 4-nonylphenol. Their aquatic predicted-no-effect concentrations (PNECs) were derived using the log-normal statistical extrapolation method. We calculated aquatic PNECs of bisphenol A and 4-nonylphenol with values of 4.01 and 0.721 ug/L, respectively. The ecological risk of each chemical in different aquatic environments near Tianjin, China, a coastal municipality along the Bohai Sea, was characterized by hazard quotient and probabilistic risk quotient assessment techniques. Hazard quotients of 7.02 and 5.99 at 2 municipal sewage sites using all of the endpoints were observed for 4-nonylphenol, which indicated high ecological risks posed by 4-nonylphenol to aquatic organisms, especially endocrine-disrupting effects. Moreover, a high ecological risk of 4-nonylphenol was indicated based on the probabilistic risk quotient method. The present results show that combining the SSWD method and the AOP concept could better protect aquatic organisms from adverse effects such as endocrine disruption and could decrease uncertainty in ecological risk assessment. Environ Toxicol Chem 2018;37:551-562. (c) 2017 SETAC. PMID- 28984378 TI - Prenatal development in greater mouse-eared bat, Myotis myotis (Borkhausen, 1797) (Chiroptera, Vespertilionidae). AB - Order Chiroptera is the second largest mammal group after rodents. An understanding of the development of the bats, which is a very special mammal group in terms of their lifestyles, morphology and their ability to fly, is very important because most of the adult anatomical differences characterizing species occur during organogenesis. In this study, developmental stages were determined for Myotis myotis species based on external morphological characteristics from embryos obtained from wild-caught pregnant females. The developmental stages of M. myotis were comparable with those of other bat species. PMID- 28984377 TI - Age- and sex-related effects in children with mild traumatic brain injury on diffusion magnetic resonance imaging properties: A comparison of voxelwise and tractography methods. AB - Although there are several techniques to analyze diffusion-weighted imaging, any technique must be sufficiently sensitive to detect clinical abnormalities. This is especially critical in disorders like mild traumatic brain injury (mTBI), where pathology is likely to be subtle. mTBI represents a major public health concern, especially for youth under 15 years of age. However, the developmental period from birth to 18 years is also a time of tremendous brain changes. Therefore, it is important to establish the degree of age- and sex-related differences. Participants were children aged 8-15 years with mTBI or mild orthopedic injuries. Imaging was obtained within 10 days of injury. We performed tract-based spatial statistics (TBSS), deterministic tractography using Automated Fiber Quantification (AFQ), and probabilistic tractography using TRACULA (TRActs Constrained by UnderLying Anatomy) to evaluate whether any method provided improved sensitivity at identifying group, developmental, and/or sex-related differences. Although there were no group differences from any of the three analyses, many of the tracts, but not all, revealed increases of fractional anisotropy and decreases of axial, radial, and mean diffusivity with age. TBSS analyses resulted in age-related changes across all white matter tracts. AFQ and TRACULA revealed age-related changes within the corpus callosum, cingulum cingulate, corticospinal tract, inferior and superior longitudinal fasciculus, and uncinate fasciculus. The results are in many ways consistent across all three methods. However, results from the tractography methods provided improved sensitivity and better tract-specific results for identifying developmental and sex-related differences within the brain. PMID- 28984379 TI - Use of polychlorinated biphenyl and toxic equivalent concentrations in scat from mink(Neovison vison) fed fish from the upper Hudson River to predict dietary and hepatic concentrations and health effects. AB - To evaluate health effects associated with consumption of fish contaminated with polychlorinated biphenyls (PCBs) from the upper Hudson River, farm-raised mink were fed diets containing fish collected from the river. Endpoints assessed included adult reproductive performance, offspring growth and mortality, and organ mass and pathology of adults and their offspring. Scat samples were collected from adult males at the time of necropsy and from adult females just prior to whelping. Scat samples were analyzed for PCBs, polychlorinated dibenzo-p dioxins (PCDDs), and polychlorinated dibenzofurans (PCDFs). The present study provides the results of these analyses and compares ?PCB and 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) toxic equivalent (TEQ) concentrations in scat with dietary and hepatic concentrations associated with effects reported previously. Dry weight concentrations of ?PCBs and ?TEQs in scat generally increased with dietary concentration and reflected corresponding increases in hepatic concentrations of ?PCBs and ?TEQs. Maternal concentrations of ?PCBs in scat expressed on a dry, wet, and lipid weight basis predicted to result in 50% kit mortality (LC50) were 1.0, 0.30, and 12 MUg ?PCBs/g. Concentrations of ?PCBs in scat expressed on a dry, wet, and lipid weight basis predicted to result in 50% incidence of a previously reported jaw lesion (EC50) were 1.7, 0.48, and 24 MUg ?PCBs/g in adult females and 2.5, 0.87, and 19 MUg ?PCBs/g in adult males. Environ Toxicol Chem 2018;37:563-575. (c) 2017 SETAC. PMID- 28984380 TI - Knotting nets: Molecular junctions of interconnecting endocrine axes identified by application of the adverse outcome pathway concept. AB - To be defined as an endocrine disruptor, a substance has to meet several criteria, including the induction of specific adverse effects, a specific endocrine mode of action, and a plausible link between both. The latter criterion in particular might not always be unequivocally determined, especially because the endocrine system consists of diverse endocrine axes. The axes closely interact with each other, and manipulation of one triggers effects on the other. The present review aimed to identify some of the many interconnections between these axes. The focus was on fish, but data obtained in studies on amphibians and mammals were considered if they assisted in closing data gaps, because most of the endocrine mechanisms are evolutionarily conserved. The review includes data both from ecotoxicological studies and on physiological processes and gives information on hormone/hormone receptor interactions or gene transcription regulation. The key events and key event relationships identified provide explanations for unexpected effects on one axis, exerted by substances suspected to act specifically on another axis. Based on these data, several adverse outcome pathway (AOP) segments are identified, describing connections between the hypothalamic-pituitary-gonadal (HPG) and hypothalamic-pituitary-thyroid (HPT) axes, the HPG and hypothalamic-pituitary-adrenal/interrenal (HPA/I) axes, and the HPT and HPA/I axes. Central key events identified across axes were altered aromatase activity as well as altered expression and function of the proteins 11beta-hydroxysteroid dehydrogenase (11beta-HSD) and steroidogenic acute regulatory (StAR) protein. Substance classes that act on more than one endocrine axis were, for example, goitrogens or aromatase inhibitors. Despite the wealth of information gathered, the present review only provides a few insights into the molecular nets of endocrine axes, demonstrating the complexity of their interconnections. Environ Toxicol Chem 2018;37:318-328. (c) 2017 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC. PMID- 28984381 TI - Longitudinal changes in knee gait mechanics between 2 and 8 years after anterior cruciate ligament reconstruction. AB - The purpose of this study was to longitudinally investigate changes in knee joint kinematics and kinetics from 2 to 8 years post-ACLR. Seventeen subjects with primary unilateral transtibial ACLR performed bilateral gait analysis approximately 2 years and 8 years post-ACLR. Seventeen matched healthy control subjects were also analyzed. Kinematic and kinetic comparisons between the ACLR and contralateral limbs over time were completed using a 2 * 2 (time, limb) repeated-measures ANOVA. Unpaired Student's t-tests were used to compare the ACLR and contralateral kinematics and kinetics to the control group. The ACLR and contralateral limbs had similar gait changes over time. Kinetic changes over time included a reduction in first (p = 0.048) and second (p < 0.001) peak extension moments, internal rotation moment (p < 0.001), adduction moment (first peak: p = 0.002, second peak: p = 0.009, impulse: p = 0.004) and an increase in peak knee flexion moment (p = 0.002). Kinematic changes over time included increases in peak knee flexion angle in the first half of stance (p = 0.026), minimum knee flexion angle in the second half of stance (p < 0.001), and average external rotation angle during stance (p = 0.007), and a reduction in average anterior femoral displacement during stance (p = 0.006). Comparison to healthy controls demonstrated improvement in some gait metrics over time. The results demonstrated longitudinal changes from 2 to 8 years after ACLR in knee joint kinetics and kinematics that have been related to clinical outcome after ACLR and the progression of knee OA, and support future larger and comprehensive investigations into long-term changes in joint mechanics in the ACLR population. (c) 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1478-1486, 2018. PMID- 28984382 TI - Association study of polymorphisms in the ABO gene and their gene-gene interactions with ischemic stroke in Chinese population. AB - AIMS: To investigate the impact of 4 single nucleotide polymorphisms (SNPs) within ABO gene and their gene-gene interactions on ischemic stroke (IS) susceptibility in Chinese Han population. METHODS: A total of 1993 participants (1375 males, 618 females) were selected, including 991 IS patients and 1002 normal controls. The SNPstats (http://bioinfo.iconcologia.net/SNPstats) was used for Hardy-Weinberg equilibrium (HWE) test. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best interaction combination among 4 SNPs within ABO gene. Logistic regression was performed to calculate the ORs (95%CI) for interaction between SNPs. RESULTS: Both rs579459 and rs505922 within ABO gene were associated with IS risk in additive and dominant models. IS risks were higher in those with minor alleles of rs579459 and rs505922 than those with wild type homozygotes, OR (95%CI) were 1.62 (1.19-2.10) and 1.69 (1.23-2.18), respectively. We did not find any relation of rs651007 and rs529565 with IS risk in both additive and dominant models. GMDR model indicated a significant two locus model (P = .0010) involving rs505922 and rs579459, indicating a potential interaction between rs505922 and rs579459, the cross-validation consistency of the two-locus models was 9/10, and the testing accuracy was 60.72%. We also found that participants with rs505922- TC/CC and rs579459- TC/CC genotype have the highest IS risk, compared to participants with rs505922- TT and rs579459- TT genotype, OR (95%CI) was 2.94 (1.28-4.66). CONCLUSIONS: We found that rs579459 and rs505922 within ABO gene and their interaction were both associated with increased IS risk in Chinese population. PMID- 28984383 TI - Evaluation of the highly sensitive chemiluminescent enzyme immunoassay "Lumipulse HBsAg-HQ" for hepatitis B virus screening. AB - BACKGROUND: Ongoing efforts in the development of HBsAg detection kits are focused on improving sensitivity and specificity. The purpose of this study was to evaluate an improved, highly sensitive quantitative assay, "Lumipulse HBsAg HQ", a chemiluminescent enzyme immunoassay designed for a fully automated instrument, the "Lumipulse G1200". METHODS: Serum samples for reproducibility, dilution, correlation, sensitivity, and specificity studies were obtained from patients at the Osaka University Hospital. Seroconversion and sensitivity panels were purchased from a commercial vender. Subtype, sensitivity panels, and HBsAg recombinant proteins with one or two amino acid substitutions were prepared in house. RESULTS: The coefficients of variation for the low, medium, and high concentration samples ranged from 1.93 to 2.55%. The HBsAg-HQ reagent for dilution testing showed good linearity in the 0.005-150 HBsAg IU/mL range and no prozone phenomenon. All 102 HBV carrier samples were positive by HBsAg-HQ, while other commercial reagents showed one or more to be negative. In the seroconversion panel, the 14-day blood sample was positive. The sensitivity against HBsAg-HQ "ad" and "ay" subtypes was 0.025 ng/mL. Comparisons among the HBsAg-HQ, HISCL, and Architect HBsAg reagents were performed using the Bland Altman plot. Specificity for 1000 seronegative individuals was 99.7%. HBsAg-HQ detected 29 positive serum among 12 231 routinely obtained serum samples, which showed concentrations of 0.005-0.05 HBsAg IU/mL. CONCLUSIONS: According to these results, the Lumipulse HBsAg-HQ assay, with a highly sensitive limit of detection of 0.005 IU/mL, may facilitate the development of a better management strategy for a considerable proportion of infected patients. PMID- 28984385 TI - Antibiotic resistance of Helicobacter pylori to 16 antibiotics in clinical patients. AB - BACKGROUND: Resistance of Helicobacter pylori (H. pylori) to antibiotics is increasing worldwide. To determine the status of H. pylori resistance and its patterns in clinical patients, an investigation utilizing susceptibility testing for commonly used antibiotics was needed. METHODS: Total of 2283 H. pylori strains were collected from 2013 to 2016. The resistance and its patterns of these strains were tested by agar dilution method. The resistance rate and minimal inhibition concentration (MIC) in different gender groups were also analyzed. RESULTS: The overall resistance rates were as following: amoxicillin (1.58%), clarithromycin (22.73%), levofloxacin (24.75%), furazolidone (1.49%), doxycycline (9.20%), cefetamet (97.20%), ceftriaxone (49.60%), cefuroxime (25.20%), gentamicin (3.73%), azithromycin (85.60%), rifampicin (2.80%), metronidazole (92.53%), ornidazole (94.27%), tinidazole (87.20%), ciprofloxacin (43.20%), and moxifloxacin (38.53%). There were only 64.08% strains pan susceptible to amoxicillin, clarithromycin, levofloxacin, and furazolidone, followed by mono resistance (23.17%), double resistance (11.13%), triple resistance (1.36%), and quadruple resistance (0.26%). Significant differences in the resistance rate and MIC were also observed in different gender groups. CONCLUSION: Antibiotic resistance trends of H. pylori is increasing in clinical patients. With the increasing resistance, it is imperative to individualized therapy based on the results of drug susceptibility testing. PMID- 28984384 TI - The role of the long non-coding RNA TDRG1 in epithelial ovarian carcinoma tumorigenesis and progression through miR-93/RhoC pathway. AB - As one of the most frequently diagnosed cancers in women, the development and progression of epithelial ovarian carcinoma (EOC) remains an open area of research. The role of long non-coding RNAs (lncRNAs) in EOC is an emerging field of study. We found that LncRNA TDRG1 (human testis development-related gene 1) was highly expressed in EOC tissues than in normal ovarian tissues, and expression differed significantly with differentiation. LncRNA TDRG1 downregulation suppressed EOC cell proliferation, migration, and invasion, while its overexpression had the opposite effect. Bioinformatic predictions and dual luciferase reporter assays showed that LncRNA TDRG1 has possible miRNA-93 (miR 93) binding sites. LncRNA TDRG1 downregulation upregulated miR-93 expression, while its overexpression reduced miR-93 expression. In addition, TDRG1 downregulation reduced the expression of Ras homolog gene family member C (RhoC), P70 ribosomal S6 kinase (P70S6 K), Bcl-xL, and matrix metalloproteinase 2 (MMP2) protein, which are regulated by miR-93, while its upregulation induced RhoC, P70S6 K, Bcl-xL, and MMP2 protein expression. In vivo, LncRNA TDRG1 overexpression induced tumor development and RhoC expression. Taken together, our results demonstrated for the first time that LncRNA TDRG1 may be a new and important diagnostic and therapeutic target in EOC. PMID- 28984386 TI - Pyogenic liver abscess related to intrahepatic bile duct stones: Difficulties in infectious control and diagnosis of concomitant cholangiocarcinoma. AB - BACKGROUND AND AIM: Cholangitis, bacteremia, and pyogenic liver abscess (PLA) can be often caused by intrahepatic bile ducts stone (IBDS), which is endemic to South-East Asia. The association between IBDS and cholangiocarcinoma has been well recognized. Concomitant cholangiocarcinoma in the PLA related to IBDS is often missed. METHODS: A case-control study consisting of 64 patients with PLA related to IBDS and 256 control patients with PLA not related to IBDS was used to investigate clinical features of PLA and incidence of concomitant cholangiocarcinoma in patients with PLA related to IBDS. RESULTS: The main imaging manifestations of PLA related to IBDS was cystic-solid lesions and solid lesions. Of seven patients (10.9%) with pathology-proven cholangiocarcinoma in the same area of PLA related to IBDS among 64 patients, only two patients were initially diagnosed as having concomitant cholangiocarcinoma by biopsy, and other five patients diagnosed as acute inflammatory lesion. Within 60 days after onset, the infection-related death rate and recurrence rate in patients with PLA related to IBDS were 12.9% and 20.3%, respectively, whereas in patients with PLA not related to IBDS were 3.9% and 3.1%, respectively. Only 25% of patients with PLA related to IBDS underwent surgery after admission. The main pathogens in PLA patients related to IBDS were Escherichia coli and extended-spectrum beta lactamase-producing Enterobacteriaceae. CONCLUSIONS: The imaging manifestations of PLA related to IBDS often present cystic-solid or solid lesions. PLA related to IBDS is characterized by high rate of recurrence and infection-related death, difficulty in diagnosis of concomitant cholangicarcinoma. PMID- 28984388 TI - Educating for collaborative practice: an interpretation of current achievements and thoughts for future directions. AB - CONTEXT: The Edinburgh Declaration, developed in 1998 as a pledge to alter the character of medical education to more effectively meet the needs of society, included a recommendation to increase the opportunity for joint learning between health and health-related professions, as part of the training for teamwork. This article acknowledges achievements since the Declaration in relation to this recommendation, using an umbrella term for the phenomenon, 'educating for collaborative practice', and presents a perspective framed as a series of questions to encourage reflection on future directions. METHODS: A literature interpretation, informed by philosophical hermeneutics, was conducted using text sets comprising reports and reviews from a section of the international literature since 1988. The interpretation involved: engaging with meanings as presented in the chosen texts; making iterative returns to the texts to explore emerging understanding; and ensuring parts of our understanding from particular texts were fused with complete understanding of the texts as a whole. A lens of appreciative inquiry facilitated acknowledgement of what has been achieved, while being curious about how it could be. RESULTS: Interpretation of the selected literature revealed notable achievements. Areas for further consideration were identified in relation to three themes: establishing shared understanding AND purpose behind use of terminology; being a conduit AND sharing responsibility for change; exploring ways of doing things AND ensuring ongoing inclusivity. CONCLUSIONS: Interpreting the current literature on 'educating for collaborative practice' has generated questions for reflection on how it may be otherwise. Readers are encouraged to embrace the tensions inherent in unanswered questions, providing space for communication, initiative and diversity of thought. An ongoing dialogue with the literature is proposed, asking whether educating students for a collective identity in settings where they are learning for and with patients is likely to advance educating for patient-centred collaborative practice. PMID- 28984387 TI - Gene expression differences in the methionine remethylation and transsulphuration pathways under methionine restriction and recovery with D,L-methionine or D,L HMTBA in meat-type chickens. AB - This study examined the molecular mechanisms of methionine pathways in meat-type chickens where birds were provided with a diet deficient in methionine from 3 to 5 weeks of age. The birds on the deficient diet were then provided with a diet supplemented with either D,L-methionine or D,L-HMTBA from 5 to 7 weeks. The diet of the control birds was supplemented with L-methionine from hatch till 7 weeks of age. We studied the mRNA expression of methionine adenosyltransferase 1, alpha, methionine adenosyltransferase 1, beta, 5-methyltetrahydrofolate homocysteine methyltransferase, 5-methyltetrahydrofolate-homocysteine methyltransferase reductase, betaine-homocysteine S-methyltransferase, glycine N methyltransferase, S-adenosyl-L-homocysteine hydrolase and cystathionine beta synthase genes in the liver, duodenum, Pectoralis (P.) major and the gastrocnemius muscle at 5 and 7 weeks. Feeding a diet deficient in dietary methionine affected body composition. Birds that were fed a methionine-deficient diet expressed genes that indicated that remethylation occurred via the one carbon pathway in the liver and duodenum; however, in the P. major and the gastrocnemius muscles, gene expression levels suggested that homocysteine received methyl from both folate and betaine for remethylation. Birds who were switched from a methionine deficiency diet to one supplemented with either D,L methionine or D,L-HMTBA showed a downregulation of all the genes studied in the liver. However, depending on the tissue or methionine form, either folate or betaine was elicited for remethylation. Thus, mRNA expressions show that genes in the remethylation and transsulphuration pathways were regulated according to tissue need, and there were some differences in the methionine form. PMID- 28984389 TI - Binding of trace elements (Ag, Cd, Co, Cu, Ni, and Tl) to cytosolic biomolecules in livers of juvenile yellow perch (Perca flavescens) collected from lakes representing metal contamination gradients. AB - Biomolecules involved in handling cytosolic metals in the liver of the yellow perch (Perca flavescens) were characterized in juvenile fish collected from 4 lakes constituting metal contamination gradients. Using size-exclusion liquid chromatography coupled to an inductively coupled mass spectrometer, we determined metal distributions among ligands of different molecular weights in the cytosol, before and after a heat denaturation step designed to isolate metallothionein like peptides and proteins. Silver, Cd, and Cu found in the heat-stable protein supernatants were indeed largely present as metallothionein-like peptide complexes; but Co, Ni, and Tl, also present in the heat-stable protein supernatants, did not coelute with metallothionein-like peptides and proteins. This difference in metal partitioning is consistent with the known preference of "soft" metals such as Ag, Cd, and Cu(I) for thiolated ligands and the contrasting tendency of Co and Ni to bind to ligands with oxygen and nitrogen as donor atoms. Metal handling in the whole cytosol also reflected these differences in metal binding behavior. For Cd and Cu, the importance of the molecular weight pool that includes metallothionein-like peptides and proteins increased relative to the other pools as the total cytosolic metal concentration ([M]cytosol ) increased, consistent with a concentration-dependent detoxification response. In contrast, for Ni and Tl the increase in [M]cytosol was accompanied by a marked increase in the high-molecular weight (670-33 kDa) pool, suggesting that hepatic Ni and Tl are not effectively detoxified. Overall, the results suggest that metal detoxification is less effective for Ni, Tl, and Co than for Ag, Cd, and Cu. Environ Toxicol Chem 2018;37:576-586. (c) 2017 SETAC. PMID- 28984390 TI - Experimental and Theoretical Interpretation on the Magnetic Behavior in a Series of Pentagonal-Bipyramidal DyIII Single-Ion Magnets. AB - Taking advantage of the steric hindrance and charge-driving effects, four air stable pentagonal bipyramidal mononuclear DyIII compounds were hydrothermally synthesized. With a tetradentate ligand, N,N'-bis(2 methylenepyridinyl)ethylenediamine (Bpen), invariably coordinates to DyIII in an equatorial plan, 1-3 achieve an orderly transformation of the ligand field by sequentially replacing the remaining sites of the DyIII ion. Compound 4 possesses the same coordination atoms but a different peripheral coordination sphere with 3. Magnetic characterizations display that the compounds are field-induced single ion magnets (SIM) with actually low barriers, even though 2 has both the same atoms and a similar geometry of the first sphere compared with [Dy(bbpen)Cl] (2', H2 bbpen=N,N'-bis(2-hydroxybenzyl)-N,N'-bis(2-methylpyridyl)ethylenediamin), a high-performance SIM previously reported. Detailed ab initio calculations have been employed to further elucidate the electronic and magnetic structure of the low-lying energy levels of compounds 1-4 and 2'. The theoretical results indicate there is an apparent difference in the electronic structure for these compounds. The analysis on the electrostatic potential further demonstrates that although the pentagonal bipyramidal D5h is one of the ideal configurations expected, the electron density of the donor atoms from the different hybridizations and other functional groups, outside the first sphere, should also be considered in the rational design of promising molecular magnets. PMID- 28984391 TI - Tuning Electron Flux through Nitrogenase with Methanogen Iron Protein Homologues. AB - Nitrogenase uses a reductase component called Fe protein to deliver electrons to its catalytic partner for substrate reduction. The essential role of Fe protein in catalysis makes it an ideal target for regulating the electron flux and enzymatic activity of nitrogenase without perturbing the cofactor site. This work reports that hybrids between the Fe protein homologs of Methanosarcina acetivorans and the catalytic components of Azotobacter vinelandii can trap substrate CO through reduced electron fluxes. In addition, homology modeling/in silico docking is used to define markers for binding energy and specificity between the component proteins that correlate with the experimentally determined activities. This homologue-based approach could be further developed to allow identification or design of hybrids between homologous nitrogenase components for mechanistic investigations of nitrogenase through capture of substrates/ intermediates or for transgenic expression of nitrogenase through synthetic biology. PMID- 28984392 TI - Spin-State Energetics of Fe Complexes from an Optimally Tuned Range-Separated Hybrid Functional. AB - We assess the performance of the optimally tuned range-separated hybrid (OT-RSH) functional approach in predicting the ground-state electronic configuration and spin-state energetics of complexes that can potentially exhibit multiple spin configurations. To that end, we investigate eight iron complexes: four spin crossover complexes, for which reference data from other approximate density functionals are available, and four smaller complexes, for which reference ab initio data are available. We show that the spin-state energetics are mostly governed by the percentage of short-range exact exchange and are only weakly influenced by the choice of the range-separation parameter. However, the electronic structure, especially the fundamental gap, is much more sensitive to the range-separation parameter. We further find that correct prediction of the ground state in spin-crossover compounds requires a reduction in the amount of short-range exact exchange, likely owing to a larger role of static correlation. PMID- 28984393 TI - In memory of Tommaso Galeotti. PMID- 28984394 TI - Impaired hypothalamic cocaine- and amphetamine-regulated transcript expression in lateral hypothalamic area and paraventricular nuclei of dehydration-induced anorexic rats. AB - Negative energy balance promotes physiological adaptations that ensure the survival of animals. The hypothalamic-pituitary-thyroid axis regulates basal energy expenditure and its down-regulating adaptation to negative energy balance is well described: in fasting, the serum content of thyrotrophin (TSH) and thyroid hormones (TH) decreases, enhancing the survival odds of individuals. By contrast, dehydration-induced anorexic (DIA) rats present an impaired hypothalamic-pituitary-thyroid (HPT) axis adaptation despite their negative energy balance: increased circulating TSH levels. The implication of cocaine- and amphetamine-regulated transcript (CART), an anorexic peptide, in HPT axis function impairment and food-avoidance behaviour displayed by DIA animals is unknown. Because CART is co-expressed with the peptide that regulates the HPT axis in hypophysiotrophic paraventricular nucleus (PVN) neurones (TSH-releasing hormone), we analysed CART expression and possible implications with respect to high TSH levels of DIA animals. We examined whether changes in CART expression from the lateral hypothalamic area (LHA) and arcuate nucleus (ARC) could participate in food-avoidance of DIA rats. DIA and forced-food restricted (FFR) animals reduced their body weight and food intake. FFR rats had a down-regulation of their HPT axis (reduced serum TH and TSH content), whereas DIA animals had reduced TH but increased TSH levels. CART mRNA expression in the ARC decreased similarly between experimental groups and diminished in anterior, medial PVN and in LHA of FFR animals, whereas DIA animals showed unchanged levels. This impaired CART mRNA expression in the anterior PVN and LHA could be related to the aberrant feeding behaviour of DIA rats but not to their deregulated HPT axis function. PMID- 28984395 TI - The cost of reproduction in women: Reproductive effort and oxidative stress in premenopausal and postmenopausal American women. AB - OBJECTIVES: Life history theory predicts a trade-off between female investment in reproduction and somatic maintenance, which can result in accelerated senescence. Oxidative stress has been shown to be a causal physiological mechanism for accelerated aging and a possible contributor to this trade-off. We aimed to test the hypothesis for the existence of significant associations between measures of reproductive effort and the level of oxidative stress biomarkers in premenopausal and postmenopausal American women. METHODS: Serum samples and questionnaire data were collected from 63 premenopausal and postmenopausal women (mean age 53.4 years), controls in the Connecticut Thyroid Health Study, between May 2010 and December 2013. Samples were analyzed for levels of 8-OHdG and Cu/Zn-SOD using immunoassay method. RESULTS: Levels of oxidative damage (8-OHdG) but not oxidative defense (Cu/Zn-SOD) were negatively associated with parity and number of sons in premenopausal women (r = -0.52 for parity, r = -0.52 for number of sons, P < .01). Together, measures of reproductive effort, women's BMI, age, and menopausal status explained around 15% of variance in level of 8-OHdG. No association between reproductive effort characteristics and oxidative damage was found for postmenopausal women. CONCLUSIONS: We found no evidence of a trade-off between somatic maintenance as measured by 8-OHdG and reproductive effort in women from this American population. On the contrary, higher gravidity and parity in premenopausal women was associated with lower damage to cellular DNA caused by oxidative stress. These results highlight the importance of population variation and environmental conditions when testing the occurrence of life-history trade offs. PMID- 28984396 TI - Association of common genetic variants with human skin color variation in Indian populations. AB - OBJECTIVES: Human skin color is one of the most conspicuously variable physical traits that has attracted the attention of physical anthropologists, social scientists and human geneticists. Although several studies have established the underlying genes and their variants affecting human skin color, they were mostly confined to Europeans and Africans and similar studies in Indian populations have been scanty. Studying the association between candidate genetic variants and skin color will help to validate previous findings and to better understand the molecular mechanism of skin color variation. METHODS: In this study, 22 candidate SNPs from 12 genes were tested for association with skin color in 299 unrelated samples sourced from nine geographical locations in India. RESULTS: Our study establishes the association of 9 SNPs with the phenotype in Indian populations and could explain ~31% of the variance in skin color. Haplotype analysis of chromosome 15 revealed a significant association of alleles G, A and C of SNPs rs1426654, rs11070627, and rs12913316, respectively, to the phenotype, and accounted for 17% of the variance. Latitude of the sampling location was also a significant factor, contributing to ~19% of the variation observed in the samples. CONCLUSIONS: These observations support the findings that rs1426654 and rs4775730 located in SLC24A5, and rs11070627 and rs12913316 located in MYEF2 and CTXN2 genes respectively, are major contributors toward skin pigmentation and would aid in further unraveling the genotype-phenotype association in Indian populations. These findings can be utilized in forensic DNA applications for criminal investigations. PMID- 28984397 TI - Intra-arterial Modulation of the Trigeminal Nerve Ganglion in Patients with Refractory Trigeminal Neuralgia. AB - BACKGROUND AND PURPOSE: Nerves and nerve ganglions are supplied by segmental arteries and the vasa nervorum, but the intra-arterial route has not been used for diagnostic or therapeutic purposes. We present the results of intra-arterial delivery of medication for modulating trigeminal nerve ganglion function in patients with refractory trigeminal neuralgia. METHODS: We administered intra arterial lidocaine in doses up to 50 mg in the middle meningeal artery territory adjacent to the arterial branch that supplies the trigeminal nerve ganglion. We performed electrophysiologic monitoring to serially assess the latency and amplitude of R1 and R2 responses in the blink reflex before and concurrent with each incremental dose of lidocaine. Clinical outcome assessment included a 10 point numeric rating, 4-point severity grading, and the pain-free time interval pre- and post-treatment. RESULTS: Intra-arterial lidocaine was administered to three patients with trigeminal neuralgia (35-year-old woman, 57-year-old man, and 34-year-old woman). In all patients, there was a latency prolongation and amplitude reduction of R1 or R2 responses or both which was evident after 5-10 mg of lidocaine administration; a more pronounced effect was seen with increasing doses. The second and third patients reported improvement in pain severity on all scales with pain-free intervals of 5 and 3 days, respectively. There was improvement in facial hyperalgesia in all three patients in all dermatomes. All three patients' symptoms had returned to baseline severity 1 month later. CONCLUSIONS: We found that modulation of trigeminal nerve activity via the intra arterial route is possible based on consistent intraprocedural electrophysiologic suppression and short-term clinical improvement in patients with refractory trigeminal neuralgia. PMID- 28984398 TI - The beta-lactam clavulanic acid mediates glutamate transport-sensitive pain relief in a rat model of neuropathic pain. AB - BACKGROUND: Following nerve injury, down-regulation of astroglial glutamate transporters (GluTs) with subsequent extracellular glutamate accumulation is a key factor contributing to hyperexcitability within the spinal dorsal horn. Some beta-lactam antibiotics can up-regulate GluTs, one of which, ceftriaxone, displays analgesic effects in rodent chronic pain models. METHODS: Here, the antinociceptive actions of another beta-lactam clavulanic acid, which possesses negligible antibiotic activity, were compared with ceftriaxone in rats with chronic constriction injury (CCI)-induced neuropathic pain. In addition, the protein expression of glutamate transporter-1 (GLT1), its splice variant GLT1b and glutamate-aspartate transporter (GLAST) was measured in the spinal cord of CCI rats. Finally, protein expression of the same GluTs was evaluated in cultured astrocytes obtained from rodents and humans. RESULTS: Repeated injection of ceftriaxone or clavulanic acid over 10 days alleviated CCI-induced mechanical hypersensitivity, whilst clavulanic acid was additionally able to affect the thermal hypersensitivity. In addition, clavulanic acid up-regulated expression of GLT1b within the spinal cord of CCI rats, whereas ceftriaxone failed to modulate expression of any GluTs in this model. However, both clavulanic acid and ceftriaxone up-regulated GLT1 expression in rat cortical and human spinal astrocyte cultures. Furthermore, clavulanic acid increased expression of GLT1b and GLAST in rat astrocytes in a dose-dependent manner. CONCLUSIONS: Thus, clavulanic acid up-regulates GluTs in cultured rodent- and human astroglia and alleviates CCI-induced hypersensitivity, most likely through up-regulation of GLT1b in spinal dorsal horn. SIGNIFICANCE: Chronic dosing of clavulanic acid alleviates neuropathic pain in rats and up-regulates glutamate transporters both in vitro and in vivo. Crucially, a similar up-regulation of glutamate transporters in human spinal astrocytes by clavulanic acid supports the development of novel beta-lactam-based analgesics, devoid of antibacterial activity, for the clinical treatment of chronic pain. PMID- 28984399 TI - Characterization of a novel capsaicin/heat ongoing pain model. AB - BACKGROUND: Human experimental pain models provide an important translational link between pre-clinical models and clinical pain. Using topical capsaicin and continuous heat application, the novel capsaicin/heat ongoing pain (CHOP) model induces long-lasting experimental pain of which the perceived intensity can be individually adjusted. METHODS: In the CHOP model, capsaicin or control cream is applied to a 10 * 10 cm skin area and a heating pad is applied over the area after cream removal. Two experiments in healthy participants were performed for model characterization. In Experiment 1, a constant temperature was applied for 60 min; in Experiment 2, temperature was adjusted to maintain a constant perceived intensity for 60 min. RESULTS: Experiment 1: across participants, constant temperature induced initial habituation followed by an increase in sensation back to baseline. Cluster analysis revealed that half the participants sensitized to the constant temperature, while the other half did not. The degree of sensitization was related to the baseline pain unpleasantness, relative to pain intensity. Experiment 2: constant perceived intensity was achieved in the painful and a non-painful control condition. The two conditions did not differ regarding possibly confounding variables, including blood pressure, heart rate, inflammation or physiological stress as measured by surrogate markers. Secondary allodynia and hyperalgesia were reported more following painful compared to control stimulation. Sensitizers as determined in Experiment 1 were also more pain sensitive in Experiment 2. CONCLUSION: The CHOP model reproduces some aspects of clinical pain, such as longer duration, sensitization, secondary allodynia and hyperalgesia. SIGNIFICANCE: Here we demonstrate a novel pain model that can be applied for up to an hour without tissue damage. The CHOP model allows for investigation of primary and secondary hyperalgesia as well as top down influences on sensitization, thereby providing an experimental model that can be used to assess clinically-oriented questions. PMID- 28984400 TI - Mutation analysis by whole exome sequencing of endometrial hyperplasia and carcinoma in one patient: Abnormalities of polymerase epsilon and the phosphatidylinositol-3 kinase pathway. AB - In order to understand the role of gene mutations in endometrial carcinogenesis, whole exome sequencing via laser microdissection was performed in the normal endometrium, atypical endometrial hyperplasia and endometrial carcinoma in the same patient. A total of 4046 and 5746 mutations with amino acid substitution were detected in endometrial hyperplasia and endometrial carcinoma, respectively; 2252 were common in both tissues and might play crucial roles in early carcinogenesis. These common mutations included polymerase epsilon (POLE) and DNA mismatch repair (MMR) genes, indicating that an ultra-mutated phenotype, and also included PTEN and PIK3CA. The mutation-prone environment evoked by mutations in the POLE and MMR genes associated with the activated phosphatidylinositol-3 kinase pathway played a pivotal role in this case. PMID- 28984401 TI - Cyclic Depsipeptide BE-43547A2 : Synthesis and Activity against Pancreatic Cancer Stem Cells. AB - Asymmetric total synthesis of the cyclic depsipeptide BE-43547A2 was achieved in 15 linear steps on a 350 mg scale in one batch. The synthesis features the highly diastereoselective construction of an alpha-hydroxy-beta-ketoamide through alpha hydroxylation with a d.r. of up to 86:1. BE-43547A2 significantly reduces the percentage of pancreatic cancer stem cells (PCSCs) in Panc-1 cell cultures, and dramatically reduces the tumorsphere-forming capability of Panc-1 cells. An in vivo tumor-initiation assay, a gold standard for cancer stem cell assays, confirmed that BE-43547A2 can abolish the tumorigenesis of Panc-1 cells. The anti PCSC activity of BE-43547A2 could make this depsipeptide scaffold a promising starting point for discovering new PCSC-targeting drugs. PMID- 28984402 TI - Efficacy, acceptability and safety of cognitive behavioural therapies in fibromyalgia syndrome - A systematic review and meta-analysis of randomized controlled trials. AB - : This updated systematic review aimed at evaluating the efficacy, acceptability and safety of cognitive behavioural therapies (CBTs) in fibromyalgia syndrome (FMS). Clinicaltrials.gov, Cochrane Library, MEDLINE, PsycINFO and SCOPUS were searched from September 2013 to May 2017. Randomized controlled trials (RCTs) comparing CBTs with controls were analysed. Primary outcomes were >=50% pain relief, >=20% improvement of health-related quality of life (HRQoL), negative mood, fatigue, disability, acceptability and safety at end of therapy and at 6 months follow-up. Effects were summarized by a random effects model using risk differences (RD) or standardized mean differences (SMD) with 95% confidence intervals (CI). 29 RCTs with 2509 subjects were included. CBTs were superior to controls (waiting list, attention control, treatment as usual, other active non pharmacological therapies) in pain relief of 50% or greater (RD 0.05 [95% CI 0.02 0.07] (high-quality evidence), improvement of HRQoL of 20% or greater (RD 0.13 [95% CI 0.00-0.26], (moderate quality evidence), and in reducing negative mood (SMD -0.43 [95% CI -0.62 to -0.24]) (high-quality evidence), disability (SMD 0.30 [95% CI -0.52 to -0.08]) (high-quality evidence) and fatigue (SMD - 0-27 [95% CI -0.50 to -0.03]) (high-quality evidence). There were no statistically significant differences between CBTs and controls in acceptability and safety (high-quality evidence). The update did not change the major findings of the previous review. CBTs provided a clinically relevant benefit over control interventions in reducing some key symptoms of FMS and disability at the end of treatment. SIGNIFICANCE: This updated systematic review with meta-analysis on cognitive behavioural therapies (CBTs) including acceptance-based CBTs endorse the efficacy and tolerability of CBTs in reducing key symptoms and disability in FMS in the short- and long-term if compared to waiting list, treatment as usual, attention controls and active non-pharmacological therapies. CBTs did not differ in efficacy except superiority for coping with pain and tolerability from recommended drug therapy (pregabalin and/or duloxetine). PMID- 28984403 TI - Radical-Based C-C Bond-Forming Processes Enabled by the Photoexcitation of 4 Alkyl-1,4-dihydropyridines. AB - We report herein that 4-alkyl-1,4-dihydropyridines (alkyl-DHPs) can directly reach an electronically excited state upon light absorption and trigger the generation of C(sp3 )-centered radicals without the need for an external photocatalyst. Selective excitation with a violet-light-emitting diode turns alkyl-DHPs into strong reducing agents that can activate reagents through single electron transfer manifolds while undergoing homolytic cleavage to generate radicals. We used this photochemical dual-reactivity profile to trigger radical based carbon-carbon bond-forming processes, including nickel-catalyzed cross coupling reactions. PMID- 28984404 TI - Towards Tuneable Retaining Glycosidase-Inhibiting Peptides by Mimicry of a Plant Flavonol Warhead. AB - Retaining glycosidases are an important class of enzymes involved in glycan degradation. To study better the role of specific enzymes in deglycosylation processes, and thereby the importance of particular glycosylation patterns, a set of potent inhibitors, each specific to a particular glycosidase, would be an invaluable toolkit. Towards this goal, we detail here a more in-depth study of a prototypical macrocyclic peptide inhibitor of the model retaining glycosidase human pancreatic alpha-amylase (HPA). Notably, incorporation of l-DOPA into this peptide affords an inhibitor of HPA with potency that is tenfold higher (Ki =480 pm) than that of the previously found consensus sequence. This represents a first successful step in converting a recently discovered natural-product-derived motif, already specific for the catalytic side-chain arrangement conserved in the active sites of retaining glycosidases, into a tuneable retaining glycosidase inhibition warhead. PMID- 28984405 TI - An empirically based conceptual framework for fostering meaningful patient engagement in research. AB - BACKGROUND: Patient engagement in research (PEIR) is promoted to improve the relevance and quality of health research, but has little conceptualization derived from empirical data. OBJECTIVE: To address this issue, we sought to develop an empirically based conceptual framework for meaningful PEIR founded on a patient perspective. METHODS: We conducted a qualitative secondary analysis of in-depth interviews with 18 patient research partners from a research centre affiliated patient advisory board. Data analysis involved three phases: identifying the themes, developing a framework and confirming the framework. We coded and organized the data, and abstracted, illustrated, described and explored the emergent themes using thematic analysis. Directed content analysis was conducted to derive concepts from 18 publications related to PEIR to supplement, confirm or refute, and extend the emergent conceptual framework. The framework was reviewed by four patient research partners on our research team. RESULTS: Participants' experiences of working with researchers were generally positive. Eight themes emerged: procedural requirements, convenience, contributions, support, team interaction, research environment, feel valued and benefits. These themes were interconnected and formed a conceptual framework to explain the phenomenon of meaningful PEIR from a patient perspective. This framework, the PEIR Framework, was endorsed by the patient research partners on our team. CONCLUSIONS: The PEIR Framework provides guidance on aspects of PEIR to address for meaningful PEIR. It could be particularly useful when patient-researcher partnerships are led by researchers with little experience of engaging patients in research. PMID- 28984406 TI - Early death and causes of death of people with intellectual disabilities: A systematic review. AB - BACKGROUND: Death of people with intellectual disabilities is considered to be earlier than for the general population. METHODS: Databases were searched for key words on intellectual disabilities and death. Strict inclusion/exclusion criteria were used. Information was extracted from selected papers, tabulated and synthesized. Prospero registration number: CRD42015020161. RESULTS: Of 19,111 retrieved articles, 27 met criteria. Death was earlier by 20 years. It has improved in recent decades; however, the same inequality gap with the general population remains. More severe intellectual disabilities, and/or additional comorbidities rendered it shortest. Standardized mortality rates showed a greater inequality for women than men. Respiratory disease and circulatory diseases (with greater congenital and lesser ischaemic disease compared with the general population) were the main causes of death. Cancer was less common, and cancer profile differed from the general population. Some deaths are potentially avoidable. All research is from high-income countries, and cause of death is surprisingly little investigated. CONCLUSIONS: Improved health care, including anticipatory care such as health checks, and initiatives addressing most relevant lifestyle behaviours and health risks are indicated. PMID- 28984407 TI - The role of frequent HIV testing in diagnosing HIV in men who have sex with men. AB - OBJECTIVES: In the UK, quarterly HIV testing is recommended for high-risk men who have sex with men (MSM). In this manuscript we determined the risk of being newly diagnosed with HIV in MSM by their HIV testing history, considering both the frequency and periodicity of testing. METHODS: Data on HIV incidence in MSM attending a sexual health clinic (SHC) in England in 2013-2014 with testing history (previous 2 years) were obtained from GUMCAD, the national sexually transmitted infection (STI) surveillance system in England. HIV testing patterns among MSM were defined using the frequency and periodicity of testing, based on 3 month intervals, in the year preceding the first attendance during the study period. Cox proportional hazards regression was used to determine the association between HIV testing pattern and time to HIV diagnosis with and without adjustment for demographic confounders. Analyses were stratified by risk stratum, with 'high risk' defined as a history of a bacterial STI in the past year. Adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) are reported. RESULTS: Among the 37 702 HIV-negative MSM attending an SHC in 2013-2014, 1105 (3%) were diagnosed with HIV infection within 1 year of their first attendance. The probability of HIV diagnosis was highest in MSM who were tested quarterly compared with those who were not tested in the past year (aHR 2.51; 95% CI 1.33 4.74); this increased 1.8-fold among high-risk MSM (aHR 4.48; 95% CI 0.97-21.17). CONCLUSIONS: The probability of subsequent HIV diagnosis was greatest in high risk MSM who were tested most frequently. Quarterly HIV testing increased the likelihood of identifying undiagnosed HIV infection and should remain a continued recommendation for high-risk MSM. PMID- 28984408 TI - Cost analysis of open radical cystectomy versus robot-assisted radical cystectomy. AB - OBJECTIVES: To perform a cost analysis comparing the cost of robot-assisted radical cystectomy (RARC) with open RC (ORC) in a UK tertiary referral centre and to identify the key cost drivers. PATIENTS AND METHODS: Data on hospital length of stay (LOS), operative time (OT), transfusion rate, and volume and complication rate were obtained from a prospectively updated institutional database for patients undergoing RARC or ORC. A cost decision tree model was created. Sensitivity analysis was performed to find key drivers of overall cost and to find breakeven points with ORC. Monte Carlo analysis was performed to quantify the variability in the dataset. RESULTS: One RARC procedure costs L12 449.87, or L12 106.12 if the robot was donated via charitable funds. In comparison, one ORC procedure costs L10 474.54. RARC is 18.9% more expensive than ORC. The key cost drivers were OT, LOS, and the number of cases performed per annum. CONCLUSION: High ongoing equipment costs remain a large barrier to the cost of RARC falling. However, minimal improvements in patient quality of life would be required to offset this difference. PMID- 28984409 TI - Development and validation of an instrument to measure nurse educator perceived confidence in clinical teaching. AB - Teaching nursing in clinical environments is considered complex and multi faceted. Little is known about the role of the clinical nurse educator, specifically the challenges related to transition from clinician, or in some cases, from newly-graduated nurse to that of clinical nurse educator, as occurs in developing countries. Confidence in the clinical educator role has been associated with successful transition and the development of role competence. There is currently no valid and reliable instrument to measure clinical nurse educator confidence. This study was conducted to develop and psychometrically test an instrument to measure perceived confidence among clinical nurse educators. A multi-phase, multi-setting survey design was used. A total of 468 surveys were distributed, and 363 were returned. Data were analyzed using exploratory and confirmatory factor analyses. The instrument was successfully tested and modified in phase 1, and factorial validity was subsequently confirmed in phase 2. There was strong evidence of internal consistency, reliability, content, and convergent validity of the Clinical Nurse Educator Skill Acquisition Assessment instrument. The resulting instrument is applicable in similar contexts due to its rigorous development and validation process. PMID- 28984410 TI - Comparison of coastal phytoplankton composition estimated from the V4 and V9 regions of the 18S rRNA gene with a focus on photosynthetic groups and especially Chlorophyta. AB - We compared the composition of eukaryotic communities using two genetic markers (18S rRNA V4 and V9 regions) at 27 sites sampled during Ocean Sampling Day 2014, with a focus on photosynthetic groups and, more specifically green algae (Chlorophyta). Globally, the V4 and V9 regions of the 18S rRNA gene provided similar images of alpha diversity and ecological patterns. However, V9 provided 20% more OTUs built at 97% identity than V4. 34% of the genera were found with both markers and, of the remnant, 22% were found only with V4 and 44% only with V9. For photosynthetic groups, V4 and V9 performed equally well to describe global communities at different taxonomic levels from the division to the genus and provided similar Chlorophyta distribution patterns. However, at lower taxonomic level, the V9 dataset failed for example to describe the diversity of Dolichomastigales (Chlorophyta, Mamiellophyceae) emphasizing the lack of V9 sequences for this group and the importance of the reference database for metabarcode analysis. We conclude that in order to address questions regarding specific groups (e.g., a given genus), it is necessary to choose the marker based not only on the genetic divergence within this group but also on the existence of reference sequences in databases. PMID- 28984411 TI - Foliar application of benzovindiflupyr shows non-fungicidal effects in wheat plants. AB - BACKGROUND: The fungicide benzovindiflupyr belongs to the class of succinate dehydrogenase inhibitors (SDHIs). Certain SDHIs have shown plant physiological effects, so-called secondary effects, that appeared to be related to the plant water status. Therefore, the effect of benzovindiflupyr on transpiration of leaves and whole wheat plants was studied under controlled conditions. Furthermore, wheat yield trials under controlled and natural drought stress in the field were conducted. RESULTS: Transpiration of detached wheat leaves was reduced by benzovindiflupyr in a dose-dependent manner. Similarly, whole-plant transpiration decreased for several days following application of this fungicide. In 16 field trials under drought stress conditions that were classified as disease-free, treatment of wheat plants at the flag leaf stage or at heading with benzovindiflupyr showed a grain yield increase (+5.2%; P <= 0.01) that was partially attributed to an increased thousand-grain weight. CONCLUSIONS: Water saving during pre-anthesis as a result of benzovindiflupyr application may be associated with better seed setting and filling under dry field conditions in wheat. The results of this research provide new insights into secondary effects of SDHIs that lead directly to yield improvements. (c) 2017 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. PMID- 28984413 TI - Strength through diversity: training overseas. PMID- 28984412 TI - Sublethal effects of four insecticides on folding and spinning behavior in the rice leaffolder, Cnaphalocrocis medinalis (Guenee) (Lepidoptera: Pyralidae). AB - BACKGROUND: The rice leaffolder, Cnaphalocrocis medinalis, is an important rice pest. The sublethal effects of chlorpyrifos, chlorantraniliprole, emamectin benzoate and spinosad were investigated on the folding and spinning behaviors of third- to fifth-instar C. medinalis larvae (L3 - L5) after insecticidal exposure of the second instar. RESULTS: A 25% lethal concentration (LC25 ) of chlorpyrifos prolonged the leaf selection time of L5, and reduced the number of binds per primary fold for L4 and L5. An LC10 of chlorantraniliprole reduced the number of binds per primary fold for L4 and increased the number of head swings per bind for L5. An LC10 of emamectin benzoate shortened the primary fold length for L5 and decreased the number of head swings per primary fold for L3 and L4 and the number of head swings per bind for L3, while an LC25 of emamectin benzoate shortened the fold length per 24 h for L5 and folding time for L3. An LC10 of spinosad lowered the fold length per 24 h and the number of head swings for L5. An LC25 of spinosad prolonged leaf selection time, and decreased primary fold length, binds per primary fold, binds per fold and fold length per 24 h in L5. CONCLUSION: Emamectin benzoate and spinosad exerted stronger sublethal effects on the folding and spinning behavior of C. medinalis than chlorpyrifos and chlorantraniliprole. These results provide better understanding of the sublethal effects of interactions of insecticides on C. medinalis. (c) 2017 Society of Chemical Industry. PMID- 28984414 TI - Appreciating Our Past-Virtual Issues. PMID- 28984417 TI - Role conflict within medical education. PMID- 28984416 TI - Domestic violence teaching in UK medical schools: a cross-sectional study. AB - BACKGROUND: Domestic violence and abuse (DVA) is a leading contributor to the physical and mental ill health of women. Recent international guidance recommends that undergraduate medical curricula should include DVA. We do not know what is currently taught about DVA to medical students in the UK. Recent international guidance recommends that undergraduate medical curricula should include DVA METHOD: Teaching leads from all UK medical schools (n = 34) were invited to participate in an 18-item online survey about what DVA education is provided, their views of this provision and any feedback provided by students. Descriptive statistics were used to analyse the data. RESULTS: A total of 25 out of 34 medical schools participated in the survey (74%). All respondents felt that there should be formal teaching on DVA in the medical curriculum. Eighty-four per cent of respondents reported that there was some formal teaching in their medical school, and 90% of these reported that it was mandatory. Of those who delivered some teaching, 52% reported that the provision was 0-2 hours in total. Most commonly content was delivered in year 4. DVA teaching was delivered in different modules, by different methods and delivered by a range of different providers. Seventy-five per cent of respondents reported that they felt the provision at their medical school was inadequate or not enough. Barriers to providing DVA education identified included time constraints, failure to perceive it as a medical problem and the assumption that it will be covered elsewhere. CONCLUSION: Most medical students in the UK receive a small amount of teaching on DVA towards the end of the curriculum. This is perceived as inadequate. PMID- 28984415 TI - Mechanisms of carbon nanotube-induced pulmonary fibrosis: a physicochemical characteristic perspective. AB - Carbon nanotubes (CNTs) are engineered nanomaterials (ENMs) with numerous beneficial applications. However, they could pose a risk to human health from occupational or consumer exposures. Rodent models demonstrate that exposure to CNTs via inhalation, instillation, or aspiration results in pulmonary fibrosis. The severity of the fibrogenic response is determined by various physicochemical properties of the nanomaterial such as residual metal catalyst content, rigidity, length, aggregation status, or surface charge. CNTs are also increasingly functionalized post-synthesis with organic or inorganic agents to modify or enhance surface properties. The mechanisms of CNT-induced fibrosis involve oxidative stress, innate immune responses of macrophages, cytokine and growth factor production, epithelial cell injury and death, expansion of the pulmonary myofibroblast population, and consequent extracellular matrix accumulation. A comprehensive understanding of how physicochemical properties affect the fibrogenic potential of various types of CNTs should be considered in combination with genetic variability and gain or loss of function of specific genes encoding secreted cytokines, enzymes, or intracellular cell signaling molecules. Here, we cover the current state of the literature on mechanisms of CNT-exposed pulmonary fibrosis in rodent models with a focus on physicochemical characteristics as principal drivers of the mechanisms leading to pulmonary fibrosis. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Respiratory Disease Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials. PMID- 28984420 TI - NOMENCLATURE FOR FACTORS OF THE HLA SYSTEM, UPDATE JANUARY/FEBRUARY 1997. PMID- 28984418 TI - 1,4-Dioxane-degrading consortia can be enriched from uncontaminated soils: prevalence of Mycobacterium and soluble di-iron monooxygenase genes. AB - Two bacterial consortia were enriched from uncontaminated soil by virtue of their ability to grow on 1,4-dioxane (dioxane) as a sole carbon and energy source. Their specific dioxane degradation rates at 30 degrees C, pH = 7 (i.e. 5.7 to 7.1 g-dioxane per g-protein per day) were comparable to those of two dioxane metabolizing archetypes: Pseudonocardia dioxanivoransCB1190 and Mycobacterium dioxanotrophicusPH-06. Based on 16S rRNA sequencing, Mycobacterium was the dominant genus. Acetylene inhibition tests suggest that dioxane degradation was mediated by monooxygenases. However, qPCR analyses targeting the tetrahydrofuran/dioxane monooxygenase gene (thmA/dxmA) (which is, to date, the only sequenced dioxane monooxygenase gene) were negative, indicating that other (as yet unknown) catabolic gene(s) were responsible. DNA sequence analyses also showed threefold to sevenfold enrichment of group 5 and group 6 soluble di-iron monooxygenase (SDIMO) genes relative to the original soil samples. Whereas biodegradation of trace levels of dioxane is a common challenge at contaminated sites, both consortia degraded dioxane at low initial concentrations (300 MUg l-1 ) below detectable levels (5 MUg l-1 ) in bioaugmented microcosms prepared with impacted groundwater. Overall, this work shows that dioxane-degrading bacteria (and the associated natural attenuation potential) exist even in some uncontaminated soils, and may be enriched to broaden bioaugmentation options for sites experiencing insufficient dioxane catabolic capacity. PMID- 28984419 TI - Diagnosis of pediatric neuroblastoma by urine cytology: A case report. AB - Neuroblastomas are embryonal tumors arising from the neuronal crest cells of the synaptic nervous system. Findings from aspiration cytology have been reported, but there have been no reports of urine cytology findings. Here, we report a case of pediatric neuroblastoma characterized by urine cytology. A 2-year-old boy presented with abdominal pain, nausea, and loss of appetite. Computed tomography revealed a large tumor in the left suprarenal region with massive infiltration into the kidney. Urinary cytology showed highly cellular clusters composed of small, round, atypical cells with little cytoplasm and high nuclear/cytoplasmic ratio; nuclear molding was also noted in some places. Immunocytochemical staining was positive for synaptophysin and chromogranin A, and neuroblastoma was suggested by urine cytology. A biopsy of the left adrenal tumor later confirmed a diagnosis of poorly differentiated neuroblastoma. Urine cytology may be useful for rapid diagnosis and management of similar cases. PMID- 28984422 TI - NOMENCLATURE FOR FACTORS OF THE HLA SYSTEM, UPDATE MARCH 1997. PMID- 28984421 TI - THE SPECIFICITY OF ANTI-HLA CLASS II MONOCLONAL ANTIBODIES IN CATTLE. AB - At the Eleventh International HLA Histocompatibility Workshop, numerous anti-HLA class II monoclonal antibodies (mAb) were tested. For several of the polymorphic mAb, one epitope for binding has been mapped within the antigen-binding site of the class II molecules. Screening of the available bovine DRB3 and DQB exon 2 sequences revealed that some of the key amino acid (AA) motifs of these epitopes were present in cattle as well, and the question was raised whether this sharing of key AA motifs might cause interspecies cross-reactivity. Eight polymorphic anti-HLA class II mAb (seven anti-HLA DRB1 and one anti-HLA DQB) were selected for analysis of their reactivity towards bovine lymphocytes. In addition, the monomorphic anti-HLA class II mAb, 7.5.10.1, was selected for analysis, as this mAb was described to detect class II polymorphism in cattle. Flow cytometry and lymphocyte microcytotoxicity testing revealed that five of the polymorphic anti HLA mAb were reactive with bovine lymphocytes. Furthermore, the anti-bovine reactivity of 7.5.10.1 was confirmed. These findings were supported by biochemical analysis. The anti-bovine reaction of the anti-HLA mAb did not correspond with the expected reaction, which was based on the presence of the AA, postulated to be responsible for recognition. Therefore, we suggest that the patterns of reactivity of the anti-HLA mAb are not always determined by one epitope. PMID- 28984423 TI - The triple-negative (CD34-/HLA-DR-/CD11b-) profile rapidly and specifically identifies an acute promyelocytic leukemia. AB - INTRODUCTION: The genetic testing to confirm or rule out an acute promyelocytic leukemia (APL) typically takes a minimum of 24-72 hours. Flow cytometric immunophenotyping (FCI) on the other hand provides rapid and objective information to differentiate APL from non-APL. METHODS: FCI features, with single tube 8-color combination using CD45, CD34, HAL-DR, CD11b, CD13, CD33, and CD117 and CD64, were compared for the 30 consecutive APL and 30 non-APL acute myeloid leukemia (AML) cases which morphologically mimicked an APL. The diagnosis was confirmed by cytogenetic or molecular genetic testing in the form of t (15:17) (q22; q21)/variant translocations or PML-RARA fusion transcript analysis. RESULTS: The APL cells lacked CD34, HLA-DR, and CD11b in 90%, 90%, and 93.3% cases, respectively. Myeloid antigens such as CD33, CD13, CD117, and CD64 were expressed in 96.7%, 96.7%, 76.7%, and 70% cases, respectively. The dual negative profiles, CD34-/HLA-DR- or HLA-DR-/CD11b-, were noted in 90% and 93.3% cases. The triple-negative (CD34-/HLA-DR-/CD11b-) profile was noted in 90% of the cases. The sensitivity, specificity, and positive predictive value (PPV) of CD34-/HLA-DR- and HLA-DR-/CD11b- profiles for the diagnosis of APL were found to be 90%, 80% & 81.1% and 93.3%, 86.7%& 87.5%, respectively. Combining the above two profiles resulted in a triple-negative profile (CD34-, HLA-DR- and CD11b-), which had a better specificity (93.3%) and positive predictive value (93.1%), with similar sensitivity. CONCLUSION: FCI is a rapid and reliable modality for the diagnosis of an APL. The triple-negative profile (CD34-/HLA-DR-/CD11b-) rapidly and specifically identifies an APL case. PMID- 28984424 TI - A Novel Spiro[acridine-9,9'-fluorene] Derivatives Containing Phenanthroimidazole Moiety for Deep-Blue OLED Application. AB - Typical pi-pi stacking and aggregation-caused quenching could be suppressed in the film-state by the spiro conformation molecular design in the field of organic light-emitting diodes (OLEDs). Herein, a novel deep-blue fluorescent material with spiro conformation, 1-(4-(tert-butyl)phenyl)-2-(4-(10-phenyl-10H spiro[acridine-9,9'-fluoren]-2-yl)phenyl)-1H-phenanthro[9,10-d]imidazole (SAF BPI), was designed and synthesized. The compound consists of spiro-acridine fluorene (SAF) as donor part and phenanthroimidazole (BPI) as acceptor part. Owing to the rigid SAF skeleton, this compound exhibits a high thermal stability with a glass transition temperature (Tg ) of 198 degrees C. The compound exhibits bipolar transporting characteristics demonstrated by the single-carrier devices. The non-doped OLEDs based on the SAF-BPI as the emitting layer shows maximum emission at 448 nm, maximum luminance of 2122 cd m-2 , maximum current efficiency (CE) of 3.97 cd A-1 , and a maximum power efficiency of 2.08 lm W-1 . The chromaticity coordinate is stable at (0.15, 0.10) at the voltage of 7-11 V. The device shows a slow efficiency roll-off with CE of 3.35 and 2.85 cd A-1 at 100 and 1000 cd m-2 , respectively. PMID- 28984425 TI - Opportunities for groundwater microbial electro-remediation. AB - Groundwater pollution is a serious worldwide concern. Aromatic compounds, chlorinated hydrocarbons, metals and nutrients among others can be widely found in different aquifers all over the world. However, there is a lack of sustainable technologies able to treat these kinds of compounds. Microbial electro remediation, by the means of microbial electrochemical technologies (MET), can become a promising alternative in the near future. MET can be applied for groundwater treatment in situ or ex situ, as well as for monitoring the chemical state or the microbiological activity. This document reviews the current knowledge achieved on microbial electro-remediation of groundwater and its applications. PMID- 28984426 TI - Caregiver knowledge and skills to safely care for pediatric tracheostomy ventilation at home. AB - OBJECTIVE: Caregivers of children using home mechanical ventilation (HMV) via tracheostomy require appropriate knowledge and skills. Existing training curricula are locally developed and content variable. We sought to develop a competency checklist to inform initial training and subsequent assessment of knowledge and skills of family caregivers. METHODS: We used a 2-step process. Candidate items were generated by synthesis of a scoping review, existing checklists, with additional items suggested by an eight member inter-professional group representing pediatric HMV programs across Canada. Following removal of duplicate items, we conducted a three-round Delphi to gain consensus on items for the KidsVent Checklist. RESULTS: The scoping review and checklists from five HMV programs identified 18 domains and 172 items; one additional domain and 83 additional items were identified by our expert group who also classified domains as mandatory or optional. We recruited 95 clinicians representing 12 Canadian paediatric HMV programs to participate in Delphi round 1 (response rate 72%; 84%, and 100% for subsequent rounds). Importance rating of the 255 items reduced them to 246 items. In the final checklist, the 19 domains comprised 14 mandatory (189 mandatory items) and 5 optional domains (57 optional items). CONCLUSIONS: We have developed the KidsVent checklist using rigorous consensus building methods, informed by participants with diverse geographic and inter-professional representation. This checklist represents knowledge and skills required to safely care for children using tracheostomy ventilation at home. Further study is required to explore the impact of this checklist on outcomes of this growing group of technology-dependent children. PMID- 28984427 TI - Knowledge gaps and research priorities in Staphylococcus aureus mastitis control. AB - This study assessed knowledge gaps and suggested research priorities in the field of Staphylococcus aureus mastitis. Staphylococcus aureus infecting the mammary gland remains a major problem to the dairy industry worldwide because of its pathogenicity, contagiousness, persistence in the cow environment, colonization of skin or mucosal epithelia, and the poor curing efficacy of treatments. Staphylococcus aureus also constitutes a threat to public health due to food safety and antibiotic usage issues and the potential for bidirectional transmission of strains between humans and dairy animals (cows and small ruminants). Gaps have been identified in (i) understanding the molecular basis for pathogenesis of S. aureus mastitis, (ii) identifying staphylococcal antigens inducing protection and (iii) determining the cell-mediated immune responses to infection and vaccination. The recommended priorities for research are (i) improved diagnostic methods for early detection of infection and intervention through treatment or management, (ii) development of experimental models to investigate the strategies used by S. aureus to survive within the mammary gland and resist treatment with anti-microbials, (iii) investigation of the basis for cow-to-cow variation in response to S. aureus mastitis, (iv) identification of the immune responses (adaptive and innate) induced by infection or vaccination and (v) antibacterial discovery programmes to develop new, more effective, narrow spectrum antibacterial agents for the treatment of S. aureus mastitis. With the availability and ongoing improvement of molecular research tools, these objectives may not be out of reach in the future. PMID- 28984430 TI - Modeling sediment transport in Qatar: Application for coastal development planning. AB - Hydrodynamics and sediment transport are key physical processes contributing to habitat structure within the marine environment. Coastal development that results in the alteration of these processes (e.g., changing water flushing and/or sedimentation rates) can have detrimental impacts on sensitive systems. This is a current, relevant issue in Qatar as its coastal regions continue to be developed, not only around the capital of Doha, but in many areas around this Arabian Gulf peninsula. The northeastern Qatari coast is comprised of diverse and sensitive flora and fauna such as seagrass and macroalgae meadows, coral reefs and patches, turtles, and dugongs that tolerate harsh environmental conditions. In the near future, this area may see a rise in anthropogenic activity in the form of coastal development projects. These projects will add to existing natural stresses, such as high temperature, high salinity, and low rates of precipitation. Consequently, there is a need to characterize this area and assess the potential impacts that these anthropogenic activities may have on the region. In the present study, a novel sediment transport model is described and used to demonstrate the potential impact of altering hydrodynamics and subsequent sediment transport along the northeastern Qatar nearshore marine environment. The developed models will be tested using potential scenarios of future anthropogenic activities forecasted to take place in the area. The results will show the effects on water and sediment behavior and provide a scientific approach for key stakeholders to make decisions with respect to the management of the considered coastal zone. Furthermore, it provides a tool and framework that can be utilized in environmental impact assessment and associated hydrodynamic studies along other areas of the Qatari coastal zone. Integr Environ Assess Manag 2018;14:240-251. (c) 2017 SETAC. PMID- 28984431 TI - What do we know about ALARA? Is our knowledge sufficient about radiation safety? AB - BACKGROUND: The aim of this study was to determine the knowledge of neurosurgeons and emergency physicians about ALARA (as low as reasonably achievable) and to gain awareness to them about this topic. METHODS: A multiple-choice survey comprising 17 questions was performed to 30 neurosurgeons and 70 emergency room doctors. RESULTS: Emergency medicine doctors, neurosurgeons, emergency medicine residents, neurosurgery residents and general practitioners participated in the survey. Sixty-six percent of participants stated that they examined more than 50 patient with headache, dizziness and head trauma in emergency service per diem and more than half of the participants stated that brain CT was performed in the event of patient's request, even if there was not an indication. 75% of the participants stated that they requested CT scan without neurological examination when the number of patients increased in the emergency room. Eighty-three percent of the participants did not think there was a safe dose limit in CT, 92% did not know the radiation dose received during brain CT, 96% did not know the meaning of the ALARA. Fifty-seven percent of the participants stated that if they informed about the criteria of ALARA, they will take into acount these criteria while requesting CT scan. CONCLUSIONS: In our country, doctors working in emergency services request brain CT needlessly because of taking into account the patient's wish and fear of malpractice. The knowledge of the neurosurgeons and emergency service doctors about ALARA is insufficient. It is necessary to educate our physicians about ALARA protocol, for taking these criteria into their consideration when requesting CT examination. For protecting the patients from the effects of ionizing radiation and reducing the economic loss of hospitals, it is necessary to increase awareness of the ALARA protocol and to increase the number of hospitals which protocol is applied. PMID- 28984432 TI - IgG4-related disease presenting as a temporal lobe tumor. PMID- 28984433 TI - Use of ultrasound in minimally invasive spinal instrumentation surgery. PMID- 28984434 TI - Training in skull base surgery: a holistic perspective. PMID- 28984435 TI - Highly Sensitive Piezocapacitive Sensor for Detecting Static and Dynamic Pressure Using Ion-Gel Thin Films and Conductive Elastomeric Composites. AB - A new class of simple and highly sensitive piezocapacitive sensors that are capable of detecting static and dynamic pressure changes is reported. The pressure sensor structure is formed by vertically sandwiching a sandpaper-molded carbon nanotube/poly(dimethylsiloxane) composite (CPC) dielectric layer between two ion-gel thin film electrodes. Such a capacitive sensor system enables the distinguishable detection of directional movement of applied pressure as well as static pressure variation by modulating ion distribution in the ion-gel thin films. The resulting capacitive pressure sensors exhibit high sensitivity (9.55 kPa-1), high durability, and low operating voltage (0.1 V). Our proposed pressure sensors are successfully applied as potential platforms for monitoring human physiological signals and finger sliding motions in order to demonstrate their capability for practical usage. The outstanding sensor performance of the pressure sensors can permit applications in wearable electronic devices for human machine connecting platforms, health care monitoring systems, and artificial skin. PMID- 28984428 TI - Fasciola and fasciolosis in ruminants in Europe: Identifying research needs. AB - Fasciola hepatica is a trematode parasite with a global distribution, which is responsible for considerable disease and production losses in a range of food producing species. It is also identified by WHO as a re-emerging neglected tropical disease associated with endemic and epidemic outbreaks of disease in human populations. In Europe, F. hepatica is mostly associated with disease in sheep, cattle and goats. This study reviews the most recent advances in our understanding of the transmission, diagnosis, epidemiology and the economic impact of fasciolosis. We also focus on the impact of the spread of resistance to anthelmintics used to control F. hepatica and consider how vaccines might be developed and applied in the context of the immune-modulation driven by the parasite. Several major research gaps are identified which, when addressed, will contribute to providing focussed and where possible, bespoke, advice for farmers on how to integrate stock management and diagnosis with vaccination and/or targeted treatment to more effectively control the parasite in the face of increasing the prevalence of infection and spread of anthelmintic resistance that are likely to be exacerbated by climate change. PMID- 28984436 TI - Less is More: A Comparison of Antibody-Gold Nanoparticle Conjugates of Different Ratios. AB - This comprehensive study is related to gold nanoparticles (GNPs) conjugated with antibodies. The goal of the study is to determine the minimal concentration of antibodies for conjugate synthesis when the conjugates have high antigen capturing activity. Two systems were studied: gold nanoparticles conjugated with monoclonal antibodies (mAb-GNP) specific to Helicobacter pylori and gold nanoparticles conjugated with polyclonal antibodies (pAb-GNP) specific to mouse immunoglobulins. Several conjugates were synthesized with different GNP-to antibody molar ratios (from 1:1 to 1:245) through nondirectional and noncovalent immobilization on a surface of GNPs with a diameter of 25.3 +/- 4.6 nm. The maximal antigen-capturing activities and equilibrium constants of the conjugates correlate with the formation of a constant hydrodynamic radius of the conjugates for mAb-GNP (GNP to antibody molar ratio 1:58) and with the stabilizing concentration by flocculation curves for pAb-GNP (GNP to antibody molar ratio 1:116). The application of the conjugates to the lateral flow immunoassay shows that the antibody concentrations used for the conjugation can be reduced (below the stabilizing concentration) without losing activity for the mAb-GNP conjugates. The findings highlight that the optimal concentration of antibodies immobilized on the surface of GNPs is not always equal to the stabilizing concentration determined by the flocculation curve. PMID- 28984437 TI - Lanthanide-Functionalized Metal-Organic Framework Hybrid Systems To Create Multiple Luminescent Centers for Chemical Sensing. AB - Metal-organic frameworks (MOFs) possess an important advantage over other candidate classes for chemosensory materials because of their exceptional structural tunability and properties. Luminescent sensing using MOFs is a simple, intuitive, and convenient method to recognize species, but the method has limitations, such as insufficient chemical selectivity and signal loss. MOFs contain versatile building blocks (linkers or ligands) with special chemical reactivity, and postsynthetic modification (PSM) provides an opportunity to exploit and expand their unique properties. The linkers in most MOFs contain aromatic subunits that can readily display luminescence after ultraviolet or visible (typically blue) excitation, and this is the main luminescent nature of most MOFs. The introduction of photoactive lanthanide ions (Ln3+) into the MOF hosts may produce new luminescent signals at different positions from that of the MOF linker, but this depends on the intramolecular energy transfer (antenna effect) from the MOF (linkers) to the Ln3+ ions. Controlling the Ln3+ content in MOF hybrids may create multiple luminescent centers. The nature of the unique luminescent centers may cause different responses to sensing species (i.e., ratiometric sensing), which may provide a new opportunity for luminescence research with applications to chemical sensing. In this Account, recent research progress on using lanthanide-functionalized MOF hybrid materials to create multiple luminescent centers for chemical sensing is described. Here we propose a general strategy to functionalize MOF hosts with lanthanide ions, compounds, or other luminescent species (organic dyes or carbon dots) and to assemble types of photofunctional hybrid systems based on lanthanide-functionalized MOFs. Five main methods were used to functionalize the MOFs and assemble the hybrid materials: in situ composition, ionic doping, ionic exchange, covalent PSM, and coordinated PSM. Through the lanthanide functionalization, multiple (double or triple) luminescent centers were created with different luminescent bands in the visible region. Because of the different luminescent natures of the lanthanide ions, MOF linkers, and other species (organic dyes or carbon dots), they display different responses to sensing species. Currently, using these strategies, we have utilized a dual-response luminescent probe to realize chemical sensing of different types of cations (Fe3+/Fe2+, Hg2+, and Cd2+), anions (Cr2O72-/CrO4- and CO32-), molecules (volatile organic compounds and O2), special air pollutants (formaldehyde), and biomarkers of food spoilage as well as pH and temperature. Additionally, we have achieved triple-luminescence-response sensing of ions (Ag+, Hg2+, and S2-) in complicated aqueous environments, which was developed using a logic operation. PMID- 28984439 TI - Enhanced Quality Factor Label-free Biosensing with Micro-Cantilevers Integrated into Microfluidic Systems. AB - Microelectromechanical systems (MEMS) have enabled the development of a new generation of sensor platforms. Acoustic sensor operation in liquid, the native environment of biomolecules, causes, however, significant degradation of sensing performance due to viscous drag and relies on the availability of capture molecules to bind analytes of interest to the sensor surface. Here, we describe a strategy to interface MEMS sensors with microfluidic platforms through an aerosol spray. Our sensing platform comprises a microfluidic spray nozzle and a microcantilever array operated in dynamic mode within a closed loop oscillator. A solution containing the analyte is sprayed uniformly through picoliter droplets onto the microcantilever surface; the micrometer-scale drops evaporate rapidly and leave the solutes behind, adding to the mass of the cantilever. This sensing scheme results in a 50-fold increase in the quality factor compared to operation in liquid, yet allows the analytes to be introduced into the sensing system from a solution phase. It achieves a 370 femtogram limit of detection, and we demonstrate quantitative label-free analysis of inorganic salts and model proteins. These results demonstrate that the standard resolution limits of cantilever sensing in dynamic mode can be overcome with the integration of spray microfluidics with MEMS. PMID- 28984438 TI - Engineering the Genetic Code in Cells and Animals: Biological Considerations and Impacts. AB - Expansion of the genetic code allows unnatural amino acids (Uaas) to be site specifically incorporated into proteins in live biological systems, thus enabling novel properties selectively introduced into target proteins in vivo for basic biological studies and for engineering of novel biological functions. Orthogonal components including tRNA and aminoacyl-tRNA synthetase (aaRS) are expressed in live cells to decode a unique codon (often the amber stop codon UAG) as the desired Uaa. Initially developed in E. coli, this methodology has now been expanded in multiple eukaryotic cells and animals. In this Account, we focus on addressing various biological challenges for rewriting the genetic code, describing impacts of code expansion on cell physiology and discussing implications for fundamental studies of code evolution. Specifically, a general method using the type-3 polymerase III promoter was developed to efficiently express prokaryotic tRNAs as orthogonal tRNAs and a transfer strategy was devised to generate Uaa-specific aaRS for use in eukaryotic cells and animals. The aaRSs have been found to be highly amenable for engineering substrate specificity toward Uaas that are structurally far deviating from the native amino acid, dramatically increasing the stereochemical diversity of Uaas accessible. Preparation of the Uaa in ester or dipeptide format markedly increases the bioavailability of Uaas to cells and animals. Nonsense-mediated mRNA decay (NMD), an mRNA surveillance mechanism of eukaryotic cells, degrades mRNA containing a premature stop codon. Inhibition of NMD increases Uaa incorporation efficiency in yeast and Caenorhabditis elegans. In bacteria, release factor one (RF1) competes with the orthogonal tRNA for the amber stop codon to terminate protein translation, leading to low Uaa incorporation efficiency. Contradictory to the paradigm that RF1 is essential, it is discovered that RF1 is actually nonessential in E. coli. Knockout of RF1 dramatically increases Uaa incorporation efficiency and enables Uaa incorporation at multiple sites, making it feasible to use Uaa for directed evolution. Using these strategies, the genetic code has been effectively expanded in yeast, mammalian cells, stem cells, worms, fruit flies, zebrafish, and mice. It is also intriguing to find out that the legitimate UAG codons terminating endogenous genes are not efficiently suppressed by the orthogonal tRNA/aaRS in E. coli. Moreover, E. coli responds to amber suppression pressure promptly using transposon insertion to inactivate the introduced orthogonal aaRS. Persistent amber suppression evading transposon inactivation leads to global proteomic changes with a notable up-regulation of a previously uncharacterized protein YdiI, for which an unexpected function of expelling plasmids is discovered. Genome integration of the orthogonal tRNA/aaRS in mice results in minor changes in RNA transcripts but no significant physiological impairment. Lastly, the RF1 knockout E. coli strains afford a previously unavailable model organism for studying otherwise intractable questions on code evolution in real time in the laboratory. We expect that genetically encoding Uaas in live systems will continue to unfold new questions and directions for studying biology in vivo, investigating the code itself, and reprograming genomes for synthetic biology. PMID- 28984429 TI - Incidence of cancer and overall risk of mortality in individuals treated with raltegravir-based and non-raltegravir-based combination antiretroviral therapy regimens. AB - OBJECTIVES: There are currently few data on the long-term risk of cancer and death in individuals taking raltegravir (RAL). The aim of this analysis was to evaluate whether there is evidence for an association. METHODS: The EuroSIDA cohort was divided into three groups: those starting RAL-based combination antiretroviral therapy (cART) on or after 21 December 2007 (RAL); a historical cohort (HIST) of individuals adding a new antiretroviral (ARV) drug (not RAL) to their cART between 1 January 2005 and 20 December 2007, and a concurrent cohort (CONC) of individuals adding a new ARV drug (not RAL) to their cART on or after 21 December 2007. Baseline characteristics were compared using logistic regression. The incidences of newly diagnosed malignancies and death were compared using Poisson regression. RESULTS: The RAL cohort included 1470 individuals [with 4058 person-years of follow-up (PYFU)] compared with 3787 (4472 PYFU) and 4467 (10 691 PYFU) in the HIST and CONC cohorts, respectively. The prevalence of non-AIDS-related malignancies prior to baseline tended to be higher in the RAL cohort vs. the HIST cohort [adjusted odds ratio (aOR) 1.31; 95% confidence interval (CI) 0.95-1.80] and vs. the CONC cohort (aOR 1.89; 95% CI 1.37-2.61). In intention-to-treat (ITT) analysis (events: RAL, 50; HIST, 45; CONC, 127), the incidence of all new malignancies was 1.11 (95% CI 0.84-1.46) per 100 PYFU in the RAL cohort vs. 1.20 (95% CI 0.90-1.61) and 0.83 (95% CI 0.70 0.99) in the HIST and CONC cohorts, respectively. After adjustment, there was no evidence for a difference in the risk of malignancies [adjusted rate ratio (RR) 0.73; 95% CI 0.47-1.14 for RALvs. HIST; RR 0.95; 95% CI 0.65-1.39 for RALvs. CONC] or mortality (adjusted RR 0.87; 95% CI 0.53-1.43 for RALvs. HIST; RR 1.14; 95% CI 0.76-1.72 for RALvs. CONC). CONCLUSIONS: We found no evidence for an oncogenic risk or poorer survival associated with using RAL compared with control groups. PMID- 28984440 TI - Rapid Detection of Abrin Toxin and Its Isoforms in Complex Matrices by Immuno Extraction and Quantitative High Resolution Targeted Mass Spectrometry. AB - Abrin expressed by the tropical plant Abrus precatorius is highly dangerous with an estimated human lethal dose of 0.1-1 MUg/kg body weight. Due to the potential misuse as a biothreat agent, abrin is in the focus of surveillance. Fast and reliable methods are therefore of great importance for early identification. Here, we have developed an innovative and rapid multiepitope immuno-mass spectrometry workflow which is capable of unambiguously differentiating abrin and its isoforms in complex matrices. Toxin-containing samples were incubated with magnetic beads coated with multiple abrin-specific antibodies, thereby concentrating and extracting all the isoforms. Using an ultrasonic bath for digestion enhancement, on-bead trypsin digestion was optimized to obtain efficient and reproducible peptide recovery in only 30 min. Improvements made to the workflow reduced total analysis time to less than 3 h. A large panel of common and isoform-specific peptides was monitored by multiplex LC-MS/MS through the parallel reaction monitoring mode on a quadrupole-Orbitrap high resolution mass spectrometer. Additionally, absolute quantification was accomplished by isotope dilution with labeled AQUA peptides. The newly established method was demonstrated as being sensitive and reproducible with quantification limits in the low ng/mL range in various food and clinical matrices for the isoforms of abrin and also the closely related, less toxic Abrus precatorius agglutinin. This method allows for the first time the rapid detection, differentiation, and simultaneous quantification of abrin and its isoforms by mass spectrometry. PMID- 28984441 TI - Molecular Recognition in the Colloidal World. AB - Colloidal self-assembly is a bottom-up technique to fabricate functional nanomaterials, with paramount interest stemming from programmable assembly of smaller building blocks into dynamic crystalline domains and photonic materials. Multiple established colloidal platforms feature diverse shapes and bonding interactions, while achieving specific orientations along with short- and long range order. A major impediment to their universal use as building blocks for predesigned architectures is the inability to precisely dictate and control particle functionalization and concomitant reversible self-assembly. Progress in colloidal self-assembly necessitates the development of strategies that endow bonding specificity and directionality within assemblies. Methodologies that emulate molecular and polymeric three-dimensional (3D) architectures feature elements of covalent bonding, while high-fidelity molecular recognition events have been installed to realize responsive reconfigurable assemblies. The emergence of anisotropic 'colloidal molecules', coupled with the ability to site specifically decorate particle surfaces with supramolecular recognition motifs, has facilitated the formation of superstructures via directional interactions and shape recognition. In this Account, we describe supramolecular assembly routes to drive colloidal particles into precisely assembled architectures or crystalline lattices via directional noncovalent molecular interactions. The design principles are based upon the fabrication of colloidal particles bearing surface exposed functional groups that can undergo programmable conjugation to install recognition motifs with high fidelity. Modular and versatile by design, our strategy allows for the introduction and integration of molecular recognition principles into the colloidal world. We define noncovalent molecular interactions as site-specific forces that are predictable (i.e., feature selective and controllable complementary bonding partners) and can engage in tunable high fidelity interactions. Examples include metal coordination and host-guest interactions as well as hydrogen bonding and DNA hybridization. On the colloidal scale, these interactions can be used to drive the reversible formation of open structures. Key to the design is the ability to covalently conjugate supramolecular motifs onto the particle surface and/or noncovalently associate with small molecules that can mediate and direct assembly. Efforts exploiting the binding strength inherent to DNA hybridization for the preparation of reversible open-packed structures are then detailed. We describe strategies that led to the introduction of dual-responsive DNA-mediated orthogonal assembly as well as colloidal clusters that afford distinct DNA-ligated close-packed lattices. Further focus is placed on two essential and related efforts: the engineering of complex superstructures that undergo phase transitions and colloidal crystals featuring a high density of functional anchors that aid in crystallization. The design principles discussed in this Account highlight the synergy stemming from coupling well-established noncovalent interactions common on the molecular and polymeric length scales with colloidal platforms to engineer reconfigurable functional architectures by design. Directional strategies and methods such as those illustrated herein feature molecular control and dynamic assembly that afford both open-packed 1D and 2D lattices and are amenable to 3D colloidal frameworks. Multiple methods to direct colloidal assembly have been reported, yet few are capable of crystallizing 2D and 3D architectures of interest for optical data storage, electronics, and photonics. Indeed, early implications are that [supra]molecular control over colloidal assembly can fabricate rationally structured designer materials from simple fundamental building blocks. PMID- 28984442 TI - High-Resolution Capillary Zone Electrophoresis with Mass Spectrometry Peptide Mapping of Therapeutic Proteins: Peptide Recovery and Post-translational Modification Analysis in Monoclonal Antibodies and Antibody-Drug Conjugates. AB - Reversed phase liquid chromatography with mass spectrometry (RPLC-MS) peptide mapping is routinely used for interrogating molecular and structural attributes such as amino acid composition, sequence variants, and post-translational modifications (PTMs) in antibody-derived therapeutics. RPLC has some limitations that often impact the analysis of certain peptides including large hydrophobic peptides, hydrophilic di-/tripeptides and glycopeptides. Capillary zone electrophoresis with mass spectrometry (CZE-MS) has great potential for peptide mapping due to high efficiency and outstanding sensitivity. In this report we demonstrate the utility of CZE-MS as an orthogonal and complementary technique to RPLC-MS for peptide mapping analyses of antibody-drug conjugates (ADCs) and their parent antibodies. This work is based on high-resolution CZE-MS separation recently developed in our group, where a mixed aqueous-organic solvent system containing N,N-dimethylacetamide (DMA) or N,N-dimethylformamide (DMF) was used to improve the separation selectivity. The results described here show several advantages of CZE-MS for the analysis of small hydrophilic di-/tripeptides, large hydrophobic peptides, glycopeptides, and hydrophobic drug-linked peptides. PMID- 28984443 TI - Investigation of Antibacterial 1,8-Cineole-Derived Thin Films Formed via Plasma Enhanced Chemical Vapor Deposition. AB - The need for low-fouling coatings for biomedical devices has prompted considerable interest in antibacterial compounds from natural and sustainable sources, such as essential oils. Herein, a tea tree oil-based precursor, 1,8 cineole, is used to fabricate antimicrobial films (denoted ppCin) by plasma enhanced chemical vapor deposition. Film properties were comprehensively characterized using a variety of surface and bulk analytical tools, and the plasma gas phase is assessed using optical emission spectroscopy, which can be correlated to ppCin film properties. Notably, film wettability increases linearly with plasma pressure, yielding water contact angles ranging from ~50 degrees to ~90 degrees . X-ray photoelectron spectroscopy reveals less oxygen is incorporated at higher pressures, likely arising from the lower density of OH(g) species. Further, we utilized H2O(v) plasma surface modification of the ppCin films to improve wettability and find this results in a substantial increase in surface oxygen content. To elucidate the role of film wettability and antibacterial properties, both as-deposited and H2O(v) plasma-modified films were exposed to Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus using glass slides and hydrocarbon films deposited from 1,7-octadiene as positive controls. Overall, bacteria attach to a similar extent on all films, including controls, yet only essential oil-based films significantly prevent biofilm formation (4-7% coverage compared to ~40% for controls). PMID- 28984445 TI - Thin-Film Electrochemistry of Single Prussian Blue Nanoparticles Revealed by Surface Plasmon Resonance Microscopy. AB - Electrochemical behaviors of Prussian blue (PB) have been intensively studied for decades because it not only serves as a model electro-active nanomaterial in fundamental electrochemistry but also a promising metal-ion storage electrode material for developing rechargeable batteries. Traditional electrochemical studies are mostly based on bulk materials, leading to an averaged property of billions of PB nanoparticles. In the present work, we employed surface plasmon resonance microscopy (SPRM) to resolve the optical cyclic voltammograms of single PB nanoparticles during electrochemical cycling. It was found that the electrochemical behavior of single PB nanoparticles nicely followed a classical thin-film electrochemistry theory. While kinetic controlled electron transfer was observed at slower scan rates, intraparticle diffusion of K+ ions began to take effect when the scan rate was higher than 60 mV/s. We further found that the electrochemical activity among individual PB nanoparticles was very heterogeneous and such a phenomenon has not been previously observed in the bulk measurements. The present work not only demonstrates the thin-film electrochemical feature of single electro-active nanomaterials for the first time, it also validates the applicability of SPRM technique to investigate a variety of metal ion-storage battery materials, with implications in both fundamental nanoelectrochemistry and electro-active materials for sensing and battery applications. PMID- 28984444 TI - Sequence and Solution Effects on the Prevalence of d-Isomers Produced by Deamidation. AB - Deamidation of asparagine is a spontaneous and irreversible post-translational modification associated with a growing list of human diseases. While pervasive, deamidation is often overlooked because it represents a relatively minor chemical change. Structural and functional characterization of this modification is complicated because deamidation of asparagine yields four isomeric forms of Asp. Herein, radical directed dissociation (RDD), in conjunction with mass spectrometry, is used to identify and quantify all four isomers in a series of model peptides that were subjected to various deamidation conditions. Although primary sequence significantly influences the rate of deamidation, it has little impact on the relative proportions of the product isomers. Furthermore, the addition of ammonia can be used to increase the rate of deamidation without significantly perturbing isomer populations. Conversely, external factors such as buffer conditions and temperature alter product distributions but exhibit less dramatic effects on the deamidation rate. Strikingly, the common laboratory and biologically significant bicarbonate buffer is found to strongly promote racemization, yielding increased amounts of d-Asp and d-isoAsp. These outcomes following deamidation have broad implications in human aging and should be considered during the development of protein-based therapeutics. PMID- 28984446 TI - Mechanochemically Sulfidated Microscale Zero Valent Iron: Pathways, Kinetics, Mechanism, and Efficiency of Trichloroethylene Dechlorination. AB - In water treatment processes that involve contaminant reduction by zerovalent iron (ZVI), reduction of water to dihydrogen is a competing reaction that must be minimized to maximize the efficiency of electron utilization from the ZVI. Sulfidation has recently been shown to decrease H2 formation significantly, such that the overall electron efficiency of (or selectivity for) contaminant reduction can be greatly increased. To date, this work has focused on nanoscale ZVI (nZVI) and solution-phase sulfidation agents (e.g., bisulfide, dithionite or thiosulfate), both of which pose challenges for up-scaling the production of sulfidated ZVI for field applications. To overcome these challenges, we developed a process for sulfidation of microscale ZVI by ball milling ZVI with elemental sulfur. The resulting material (S-mZVIbm) exhibits reduced aggregation, relatively homogeneous distribution of Fe and S throughout the particle (not core shell structure), enhanced reactivity with trichloroethylene (TCE), less H2 formation, and therefore greatly improved electron efficiency of TCE dechlorination (epsilone). Under ZVI-limited conditions (initial Fe0/TCE = 1.6 mol/mol), S-mZVIbm gave surface-area normalized reduction rate constants (k'SA) and epsilone that were ~2- and 10-fold greater than the unsulfidated ball-milled control (mZVIbm). Under TCE-limited conditions (initial Fe0/TCE = 2000 mol/mol), sulfidation increased kSA and epsilone ~ 5- and 50-fold, respectively. The major products from TCE degradation by S-mZVIbm were acetylene, ethene, and ethane, which is consistent with dechlorination by beta-elimination, as is typical of ZVI, iron oxides, and/or sulfides. However, electrochemical characterization shows that the sulfidated material has redox properties intermediate between ZVI and Fe3O4, mostly likely significant coverage of the surface with FeS. PMID- 28984447 TI - Magnetic Structure and Excitations in CeCuxAl4-x System. AB - CeCuAl3 crystallizing in the tetragonal BaNiSn3-type structure and CeCuxAl4-x solid solutions were investigated by means of elastic and inelastic neutron scattering. Powder neutron diffraction brought information on both temperature evolution of crystallographic parameters and magnetic order at low temperatures. No structural change was observed in the investigated temperature range from 1.5 to 300 K. Weak magnetic peaks outside nuclear Bragg positions observed in solid solutions with 0.90 <= x <= 1.10 were described by the propagation vector k = (0.40 + deltax, 0.60 + deltay, 0), where deltax ~ 0.02 and deltay ~ 0.01. The magnetic structure of CeCu0.75Al3.25 consists of two components: an anti ferromagnetic one described by the same k and a ferromagnetic one with k0 = (0, 0, 0) and magnetic moments lying within the tetragonal basal plane. The evolution of magnetic excitations as a function of Cu-Al concentration in CeCuxAl4-x was studied by inelastic neutron scattering. The measured spectra of CeCuAl3 and the solution with x = 0.95 point to a three-magnetic-peak energy scheme, while only two excitations are expected from the local symmetry conditions on Ce atoms. The standard two-peak spectrum of crystal electric field excitations was observed for Cu-Al substitutions further from the 1:1:3 stoichiometry (x = 0.75 and 1.10). The intermediate concentrations (x = 0.90 and 1.05) exhibit spectra on the border between the former cases with a less clear pronounced first inelastic magnetic peak. The observed behavior is discussed considering the evolution of structural parameters in the CeCuxAl4-x system and the coupling between the lattice vibrations and the crystal electric field excitations. PMID- 28984448 TI - Alteration of Intraligand Donor-Acceptor Interactions Through Torsional Connectivity in Substituted Re-dppz Complexes. AB - The ground- and excited-state properties of a series of [ReCl(CO)3(dppz)] complexes with substituted donor groups were investigated. Alteration of donor acceptor communication through modulation of torsional angle and the number and nature of the donor substituents allowed the effects on the photophysical properties to be characterized though both computational and spectroscopic techniques, including time-dependent density functional theory and resonance Raman and time-resolved infrared spectroscopy. The ground-state optical properties show significant variation as a result of donor group modulation, with an increased angle between the donor and acceptor blue-shifting and depleting the intensity of the lowest-energy transition, which is consistently intraligand charge transfer (ILCT) in nature. However, across all complexes studied there was minimal perturbation to the excited-state properties and dynamics. Three excited states on the picosecond, nanosecond, and microsecond time scales were observed in all cases, corresponding to 1ILCT, 3pipi*, and 3ILCT, respectively. PMID- 28984449 TI - Thermodynamic Stability Trend of Cubic Perovskites. AB - Stability is of central importance in current perovskite solar cell research and applications. Goldschmidt tolerance factor (t) recently provided qualitative guidance for experimentalists to engineer stable ABX3 perovskite by tuning effective ionic size with mixing cations or anions and for theorists to search emerging perovskites. Through first-principles calculations, we have calculated decomposition energies of 138 perovskite compounds of potential solar cell applications. Instead of t, we have found that (MU + t)eta, where MU and eta are the octahedral factor and the atomic packing fraction, respectively, demonstrates a remarkably linear correlation with thermodynamic stability. As a stability descriptor, (MU + t)eta is able to predict the relative stability among any two perovskites with an accuracy of ~90%. This trend is then used to predict decomposition energies of another 69 perovskites, and the results are in excellent agreement with first-principles calculations, indicating the generalization of the trend. This thermodynamic stability trend may help the efficient high-throughput search for emerging stable perovskites and precise control of chemical compositions for stabilizing current perovskites. PMID- 28984450 TI - Cadmium Bis(phenyldithiocarbamate) as a Nanocrystal Shell-Growth Precursor. AB - Cadmium bis(phenyldithiocarbamate) [Cd(PTC)2] is prepared and structurally characterized. The compound crystallizes in the monoclinic space group P21/n. A one-dimensional polymeric structure is adopted in the solid state, having bridging PTC ligands and 6-coordinate pseudo-octahedral Cd atoms. The compound is soluble in DMSO, THF, and DMF and insoluble in EtOH, MeOH, CHCl3, CH2Cl2, and toluene. {CdSe[n-octylamine]0.53} quantum belts and Cd(PTC)2 react to deposit epitaxial CdS shells on the nanocrystals. With an excess of Cd(PTC)2, the resulting thick shells contain spiny CdS nodules grown in the Stranski-Krastanov mode. Stoichiometric control affords smooth, monolayer CdS shells. A base catalyzed reaction pathway is elucidated for the conversion of Cd(PTC)2 to CdS, which includes phenylisothiocyanate and aniline as intermediates, and 1,3 diphenylthiourea as a final product. PMID- 28984451 TI - Membrane-Active Hydantoin Derivatives as Antibiotic Agents. AB - Hydantoin (imidazolidinedione) derivatives such as nitrofurantoin are small molecules that have aroused considerable interest recently due to their low rate of bacterial resistance. However, their moderate antimicrobial activity may hamper their application combating antibiotic resistance in the long run. Herein, we report the design of bacterial membrane-active hydantoin derivatives, from which we identified compounds that show much more potent antimicrobial activity than nitrofurantoin against a panel of clinically relevant Gram-positive and Gram negative bacterial strains. These compounds are able to act on bacterial membranes, analogous to natural host-defense peptides. Additionally, these hydantoin compounds not only kill bacterial pathogens rapidly but also prevent the development of methicillin-resistant Staphylococcus aureus (MRSA) bacterial resistance under the tested conditions. More intriguingly, the lead compound exhibited in vivo efficacy that is much superior to vancomycin by eradicating bacteria and suppressing inflammation caused by MRSA-induced pneumonia in a rat model, demonstrating its promising therapeutic potential. PMID- 28984453 TI - Selective Synthesis of 3-Arylbenzo-1,2,3-triazin-4(3H)-ones and 1-Aryl-(1H)-benzo 1,2,3-triazoles from 1,3-Diaryltriazenes through Pd(0) Catalyzed Annulation Reactions. AB - Pd(0) catalyzed carbonylative annulation reaction of 1-(2-iodophenyl)-3-aryltriaz 1-enes in the presence of DABCO and 1 atm of carbon monoxide in toluene at 80 degrees C gave the corresponding 3-arylbenzo-1,2,3-triazin-4(3H)-ones with high selectivity and in excellent yields. Substrate scope of this reaction is demonstrated with 24 examples with various halo, alkyl, and alkoxy substituents on either of the aromatic rings. Bromo substituted triazenes were less reactive as starting materials toward the carbonylative annulation reaction and yielded 3 arylbenzo-1,2,3-triazin-4(3H)-ones in good to moderate yields in the presence of only xantphos as an additive. In the absence of CO (under N2 atmosphere), the reaction did not proceed, and only starting material was recovered. However, in the presence of catalytic amount of CO or in the presence of Ph3P in catalytic amounts as additives, the reactions proceeded to yield the corresponding 1-aryl (1H)-benzo-1,2,3-triazoles selectively in good yields. On the basis of control experiments, a plausible reaction mechanism for the selective formation of 3 arylbenzo-1,2,3-triazin-4(3H)-ones in the presence of CO and1-aryl-(1H)-benzo 1,2,3-triazoles in the absence of CO through a common intermediate was proposed. PMID- 28984452 TI - C-Methylated Flavonoid Glycosides from Pentarhizidium orientale Rhizomes and Their Inhibitory Effects on the H1N1 Influenza Virus. AB - Thirteen C-methylated flavonoid glycosides (1-13), along with 15 previously known flavonoids (14-28), were isolated from rhizomes of Pentarhizidium orientale. Among these compounds, matteuorienates D-K (1-8) were obtained as analogues of matteuorienates A-C (14-16), which contain a characteristic 3-hydroxy-3 methylglutaryl (HMG) moiety. The structures of 1-13 were characterized by spectroscopic analysis and chemical derivatization. The isolates were evaluated for their antiviral activities against influenza virus (H1N1), with compounds 21, 22, 23, 25, and 26 showing inhibitory effects (IC50 of 23.9-30.3 MUM) against neuraminidases. PMID- 28984454 TI - Photochemical Relaxation Pathways in Dinitropyrene Isomer Pollutants. AB - Dinitropyrenes are polycyclic aromatic pollutants prevalent in the environment. While their transformations by sunlight in the environment have been documented, the effect that the nitro-group substitution pattern has on the relaxation pathways has not been extensively studied. In this contribution, the steady-state and femtosecond-to-microsecond excited-state dynamics of 1,3-dinitropyrene and 1,8-dinitropyrene isomers are investigated upon visible light excitation at 425 nm and compared with those recently reported for the 1,6-dinitropyrene isomer. The experimental results are complemented with ground- and excited-state density functional calculations. It is shown that excitation at 425 nm results in the ultrafast branching of the excited-state population in the S1 state to populate the triplet state in ca. 90% yield and to form a nitropyrenoxy radical in less than 10% yield. In addition, the position of the NO2 group does not affect significantly the excited-state relaxation mechanism, while it does influence the absorption and fluorescence spectra, the fluorescence, triplet, singlet oxygen, and photodegradation yields, as well as the relative yield of radical formation. Radical formation is implicated in the photodegradation of these pollutants, while in the presence of hydrogen donors, direct reactions from the triplet state are also observed. PMID- 28984455 TI - Mechanistic Insights into the Alternating Copolymerization of Epoxides and Cyclic Anhydrides Using a (Salph)AlCl and Iminium Salt Catalytic System. AB - Mechanistic studies involving synergistic experiment and theory were performed on the perfectly alternating copolymerization of 1-butene oxide and carbic anhydride using a (salph)AlCl/[PPN]Cl catalytic pair. These studies showed a first-order dependence of the polymerization rate on the epoxide, a zero-order dependence on the cyclic anhydride, and a first-order dependence on the catalyst only if the two members of the catalytic pair are treated as a single unit. Studies of model complexes showed that a mixed alkoxide/carboxylate aluminum intermediate preferentially opens cyclic anhydride over epoxide. In addition, ring-opening of epoxide by an intermediate comprising multiple carboxylates was found to be rate determining. On the basis of the experimental results and analysis by DFT calculations, a mechanism involving two catalytic cycles is proposed wherein the alternating copolymerization proceeds via intermediates that have carboxylate ligation in common, and a secondary cycle involving a bis-alkoxide species is avoided, thus explaining the lack of side reactions until the polymerization is complete. PMID- 28984456 TI - Mechanism Underlying the Nucleobase-Distinguishing Ability of Benzopyridopyrimidine (BPP). AB - Benzopyridopyrimidine (BPP) is a fluorescent nucleobase analogue capable of forming base pairs with adenine (A) and guanine (G) at different sites. When incorporated into oligodeoxynucleotides, it is capable of differentiating between the two purine nucleobases by virtue of the fact that its fluorescence is largely quenched when it is base-paired to guanine, whereas base-pairing to adenine causes only a slight reduction of the fluorescence quantum yield. In the present article, the photophysics of BPP is investigated through computer simulations. BPP is found to be a good charge acceptor, as demonstrated by its positive and appreciably large electron affinity. The selective quenching process is attributed to charge transfer (CT) from the purine nucleobase, which is predicted to be efficient in the BPP-G base pair, but essentially inoperative in the BPP-A base pair. The CT process owes its high selectivity to a combination of two factors: the ionization potential of guanine is lower than that of adenine, and less obviously, the site occupied by guanine enables a greater stabilization of the CT state through electrostatic interactions than the one occupied by adenine. The case of BPP illustrates that molecular recognition via hydrogen bonding can enhance the selectivity of photoinduced CT processes. PMID- 28984457 TI - Synthesis of Diverse o-Arylthio-Substituted Diaryl Ethers by Direct Oxythiolation of Arynes with Diaryl Sulfoxides Involving Migratory O-Arylation. AB - A diverse range of o-arylthio-substituted diaryl ethers has been synthesized by direct oxythiolation of arynes with diaryl sulfoxides that involves the formation of the C-O and C-S bonds followed by migratory O-arylation. PMID- 28984458 TI - Pr2FeCrO6: A Type I Multiferroic. AB - We synthesized double perovskite Pr2FeCrO6 by solid-state method. Analysis of its X-ray powder diffraction shows that the compound crystallizes in a centrosymmetric structure with space group Pbnm. Our X-ray photoelectron spectroscopy (XPS) studies show that all the cations are present in +3 oxidation state. Magnetization studies of Pr2FeCrO6 show that the material is paramagnetic at room temperature and undergoes a magnetic transition below TCM = 250 K. We observe clear magnetic hysteresis loop, for example, below 150 K. A low remnant magnetization Mr, ~0.05 MUB/f. u., is inferred from the observed magnetic hysteresis loop. 57Fe Mossbauer study at 25 K shows a high hyperfine magnetic field of ~53 T at the Fe nucleus, which corresponds to a magnetic moment of ~6-7 MUB/Fe. These two results together suggest a ferrimagnetic (nearly compensated or canted) ordering of the Fe moments. Mossbauer studies close to the ferrimagnetic ordering temperature suggest interesting magnetic relaxation effects. A dielectric anomaly observed at TCE = 453 K signals a ferroelectric <-> paraelectric phase transition. We observe at room temperature a clear and well defined ferroelectric hysteresis loop, PS = 1.04 MUC/cm2, establishing ferroelectricity in the material. From these results, we conclude that Pr2FeCrO6 is a type I multiferroic (TCE > TCM). PMID- 28984459 TI - Tension Independence of Lipid Diffusion and Membrane Viscosity. AB - The diffusion of biomolecules at lipid membranes is governed by the viscosity of the underlying two-dimensionally fluid lipid bilayer. For common three dimensional fluids, viscosity can be modulated by hydrostatic pressure, and pressure-viscosity data have been measured for decades. Remarkably, the two dimensional analogue of this relationship, the dependence of molecular mobility on tension, has to the best of our knowledge never been measured for lipid bilayers, limiting our understanding of cellular mechanotransduction as well as the fundamental fluid mechanics of membranes. Here we report both molecular-scale and mesoscopic measures of fluidity in giant lipid vesicles as a function of mechanical tension applied using micropipette aspiration. Both molecular-scale data, from fluorescence recovery after photobleaching, and micron-scale data, from tracking the diffusion of phase-separated domains, show a surprisingly weak dependence of viscosity on tension, in contrast to predictions of recent molecular dynamics simulations, highlighting fundamental gaps in our understanding of membrane fluidity. PMID- 28984460 TI - Thermal-Annealing-Induced Self-Stretching: Fabrication of Anisotropic Polymer Particles on Polymer Films. AB - Designing anisotropic particles of various shapes draws great attention to scientists nowadays. We develop a facile and simple method to fabricate anisotropic polymer particles from spherical polymer particles. Poly(vinyl alcohol) (PVA) films spin-coated with polystyrene (PS) microspheres are confined on both sides using binder clips and are heated above the glass-transition temperatures of the polymers. During the thermal annealing process, the PS particles sink into the PVA films and transform to anisotropic particles. Depending on the distances to the bound regions, oblate spheroid PS particles or prolate spheroid particles with different aspect ratios can be obtained. The transformation of the particles is mainly driven by the stretching forces and the squeezing forces. The main advantage of this method is that anisotropic particles with different shapes can be fabricated simultaneously on a single film. We expect that this novel method can be helpful to various fields including colloids science, suspension rheology, and drug delivery. PMID- 28984461 TI - Multiple Physical Time Scales and Dead Time Rule in Few-Nanometers Sized Graphene SiOx-Graphene Memristors. AB - The resistive switching behavior in SiOx-based phase change memory devices confined by few nanometer wide graphene nanogaps is investigated. Our experiments and analysis reveal that the switching dynamics is not only determined by the commonly observed bias voltage dependent set and reset times. We demonstrate that an internal time scale, the dead time, plays a fundamental role in the system's response to various driving signals. We associate the switching behavior with the formation of microscopically distinct SiOx amorphous and crystalline phases between the graphene electrodes. The reset transition is attributed to an amorphization process due to a voltage driven self-heating; it can be triggered at any time by appropriate voltage levels. In contrast, the formation of the crystalline ON state is conditional and only occurs after the completion of a thermally assisted structural rearrangement of the as-quenched OFF state which takes place within the dead time after a reset operation. Our results demonstrate the technological relevance of the dead time rule which enables a zero bias access of both the low and high resistance states of a phase change memory device by unipolar voltage pulses. PMID- 28984462 TI - Ir/Zn Dual Catalysis: Enantioselective and Diastereodivergent alpha-Allylation of Unprotected alpha-Hydroxy Indanones. AB - A one-step enantioselective and diastereodivergent alpha-allylation of unprotected alpha-hydroxy indanones has been developed using an Ir/Zn dual catalyst system; no additional base is required. The cyclic tertiary alpha hydroxyketones containing vicinal stereocenters can be synthesized with excellent enantioselectivity (up to >99% ee) and good diastereoselectivity (up to 12:1 dr). By a simple choice of the appropriate chiral metal catalyst combination, all four product stereoisomers could be obtained from the same starting materials and under identical conditions. PMID- 28984463 TI - Energy-Transfer Phenomena in Thermoresponsive and pH- Switchable Fluorescent Diblock Copolymer Vesicles. AB - We describe the development of a polymeric vesicle that not only selectively fluoresces at low pH, a condition prevailing in cancer cells, but also can potentially monitor the thermoresponsive release of a drug even if the drug is nonfluorescent. The developed fluorescence resonance energy transfer (FRET)-based thermoresponsive vesicular nanocarriers are composed of a new poly(PEGMA)-b poly(NIPA-r-R6GMED) block copolymer, which undergoes pH-switchable superior turn on-off fluorescence characteristics. The block copolymer was synthesized using the RAFT technique, and its solution properties and self-assembly behavior were investigated by turbidity measurements, fluorescence spectroscopy, 1H NMR, dynamic light scattering, and transmission electron microscopy. The block copolymer self-assembled to form nanostructured vesicles above the critical aggregation temperature under physiologically relevant conditions. Steady-state and time-resolved fluorescence spectroscopy were utilized to study the FRET process between encapsulated hydrophobic guest C-153 (donor) and polymer-bound R6GMED units (acceptor) in the thermoresponsive vesicles. The FRET rate and efficiency were found to vary as a result of the pH-dependent changes in the quantum yield of the acceptor molecules. The occurrence of a highly efficient FRET in this polymeric vesicular nanocarrier at acidic pH, a condition similar to the cytoplasm and cell nucleus in leukemic tissues, and the ability to encapsulate hydrophilic and hydrophobic molecules and their temperature controlled release make it potentially useful in imaging guided real-time monitoring of drug-delivery vehicles. PMID- 28984465 TI - Combination Therapy and the Start of a New Epoch for Idiopathic Pulmonary Fibrosis? PMID- 28984464 TI - Subsequent malignant neoplasms in the survivor of childhood cancer: where we have been and where we are going? PMID- 28984466 TI - Why should we perform a D2 lymphadenectomy in gastric cancer? PMID- 28984467 TI - The 9p21 Rs 1333040 polymorphism is associated with coronary microvascular obstruction in ST-segment elevation myocardial infarction treated by primary angioplasty. AB - BACKGROUND: Microvascular obstruction (MVO) after primary percutaneous coronary intervention (pPCI) leads to higher incidence of both early and late complications. A number of single nucleotide polymorphisms in 9p21 chromosome have been shown to affect angiogenesis in response to ischaemia. In particular, Rs1333040 with its three genotypic vriants C/C, T/C and T/T might influence the occurrence of MVO after pPCI. METHODS: We enrolled ST-elevation myocardial infarction (STEMI) patients undergoing pPCI. The Rs1333040 polymorphism was evaluated by polymerase chain reaction-restriction fragment length polymorphism using restriction endonucleases (Bsml). Two expert operators unaware of the patients' identity performed the angiographic analysis; collaterals were assessed applying Rentrop's classification. Angiographic MVO was defined as a post-pPCI Thrombolysis In Myocardial Infarction (TIMI)<3 or TIMI 3 with myocardial blush grade 0 or 1, whereas electrocardiographic MVO was defined as ST segment resolution <70% one hour after pPCI. RESULTS: Among our 133 STEMI patients (mean age 63 +/- 11 years, men 72%), 35 (26%) and 53 (40%) respectively experienced angiographic or electrocardiographic MVO. Angiographic and electrocardiographic MVO were different among the three variants ( p= 0.03 and p=0.02 respectively). In particular, T/T genotype was associated with a higher incidence of both angiographic and electrocardiographic MVO compared with C/C genotype ( p=0.04 and p=0.03 respectively). Moreover, Rentrop score <2 detection rate differed among the three genotypes ( p=0.03). In particular T/T genotype was associated with a higher incidence of a Rentrop score <2 as compared with C/C genotype ( p= 0.02). CONCLUSION: Rs1333040 polymorphism genetic variants portend different MVO incidence. In particular, T/T genotype is related to angiographic and electrocardiographic MVO and to worse collaterals towards the culprit artery. PMID- 28984468 TI - TGF-beta1 Evokes Human Airway Smooth Muscle Cell Shortening and Hyperresponsiveness via Smad3. AB - Transforming growth factor beta1 (TGF-beta1), a cytokine whose levels are elevated in the airways of patients with asthma, perpetuates airway inflammation and modulates airway structural cell remodeling. However, the role of TGF-beta1 in excessive airway narrowing in asthma, or airway hyperresponsiveness (AHR), remains unclear. In this study, we set out to investigate the direct effects of TGF-beta1 on human airway smooth muscle (HASM) cell shortening and hyperresponsiveness. The dynamics of AHR and single-cell excitation-contraction coupling were measured in human precision-cut lung slices and in isolated HASM cells using supravital microscopy and magnetic twisting cytometry, respectively. In human precision-cut lung slices, overnight treatment with TGF-beta1 significantly augmented basal and carbachol-induced bronchoconstriction. In isolated HASM cells, TGF-beta1 increased basal and methacholine-induced cytoskeletal stiffness in a dose- and time-dependent manner. TGF-beta1-induced single-cell contraction was corroborated by concomitant increases in myosin light chain and myosin phosphatase target subunit 1 phosphorylation levels, which were attenuated by small interfering RNA-mediated knockdown of Smad3 and pharmacological inhibition of Rho kinase. Strikingly, these physiological effects of TGF-beta1 occurred through a RhoA-independent mechanism, with little effect on HASM cell [Ca2+]i levels. Together, our data suggest that TGF-beta1 enhances HASM excitation-contraction coupling pathways to induce HASM cell shortening and hyperresponsiveness. These findings reveal a potential link between airway injury repair responses and bronchial hyperreactivity in asthma, and define TGF-beta1 signaling as a potential target to reduce AHR in asthma. PMID- 28984469 TI - Reply to Patel et al.: Tempering the Clinical Effects of Early Myeloid-derived Suppressor Cell Expansion in Severe Sepsis and Septic Shock. PMID- 28984471 TI - Tempering the Clinical Effects of Early Myeloid-derived Suppressor Cell Expansion in Severe Sepsis and Septic Shock. PMID- 28984470 TI - Advances in systemic therapy for malignant mesothelioma: future perspectives. AB - Malignant mesothelioma is a rare and aggressive form of cancer affecting the mesothelium. This mainly occupational disease is becoming more common in those countries where asbestos has been used for industrial applications. Notwithstanding the progress made in the field, patients do not survive more than 12 months on average with standard treatment. With the advent of next generation sequencing, it is now possible to study the mutational landscape of each tumor with the aim of identifying the genetic aberrations driving tumorigenesis. This review encompasses the latest research in the field, with particular attention to new chemotherapy combinatorial regimens, molecular targets and immunotherapies, providing a comprehensive picture of the current and future treatment options for malignant mesothelioma patients. PMID- 28984472 TI - Sanger Institute series: uncovering the genetics of cancer: an interview with David Adams. AB - Dr David Adams speaks to Editor of Oncology Central, Jade Parker: Based at Wellcome Trust Sanger Institute as a senior group leader, David Adams uses DNA sequencing of patients and genetic screens in human cells and mice to identify cancer genes and genetic interactions. The Adams group studies the mechanisms of cancer development, particularly skin cancer (melanoma) and colorectal cancer. They sequence DNA from families with a high incidence of cancer and also tumors from patients to understand why some people are at greater risk of tumor development and how cancers evolve. The group also performs functional studies in cultured cells and in mice to understand how factors such as DNA mutations and the immune system influence tumor growth. PMID- 28984475 TI - Sarah Tilton Fries, MPH (1938-2017). PMID- 28984476 TI - Two new 2-(2-Hydroxy-2-phenylethyl)chromens from agarwood originating from Aquilaria crassna. AB - Two new 2-(2-hydroxy-2-phenylethyl)chromones (1-2), along with three known 2-(2 phenylethyl)chromones (3-5), were isolated from the agarwood originating from Aquilaria crassna Pierre ex Lecomte. Their structures were determined by the spectroscopic methods including 1D and 2D NMR analysis and comparison with reported data in the literature. All the compounds were isolated from agarwood of A. crassna for the first time. Compounds 1 and 2 exhibited inhibitory activity against acetylcholinesterase (AChE) with 17.4 +/- 0.6 and 15.8 +/- 0.7%, respectively, at a concentration of 50 MUg/ml. Besides, Compound 3 expressed antibacterial activities against Ralstonia solanacearum with diameter of the inhibition zone of 6.80 +/- 0.08 mm at a concentration of 10 mg/ml. PMID- 28984474 TI - S100A6 promotes proliferation of intrahepatic cholangiocarcinoma cells via the activation of the p38/MAPK pathway. AB - AIM: We explored the expression of S100A6 and its role in intrahepatic cholangiocarcinoma (ICC). METHODS: The expression of S100A6 in ICC samples was detected by immunohistochemistry. In vitro experiments, we silenced and overexpressed S100A6 to investigate its role in cell functions. RESULTS: The expression of S100A6 was markedly increased in ICC tissues and cell lines. S100A6 overexpression was an independent risk factor for patients' survival. Silencing S100A6 resulted in a suppression of proliferation and p38/MAPK activity, while overexpressing S100A6 caused a promotion of proliferation and p38/MAPK. DISCUSSION: S100A6 participated in the proliferation of ICC cells and correlated with a more aggressive behavior of ICC. Conclusion: S100A6 may serve as a novel prognostic marker and a potential therapeutic target for ICC patients. PMID- 28984477 TI - Pediatric pharmacoepidemiology - safety and effectiveness of medicines for ADHD. AB - INTRODUCTION: Attention-deficit hyperactivity disorder (ADHD) is a common neurobehavioral disorder in children and adolescents that comprises core symptoms of developmentally inappropriate levels of inattention and/or hyperactivity and impulsivity. Stimulant (methylphenidate, amphetamines) and non stimulant (atomoxetine, clonidine and guanfacine) are the treatment usually prescribed for ADHD. Area covered: This review covers the safety of ADHD medications in children and adolescents. MEDLINE, EMBASE and PsycINFO databases were searched with the aim to retrieve prospective studies that monitored the incidence of adverse events (AEs) in children receiving drug therapy for ADHD. Many of the studies investigated the risk of specific AEs. In particular, the cardiovascular safety, the impact on growth and on sleep pattern, the risk of substance use disorders and of suicidal ideation are among the topics more studied. Expert opinion: Effective drugs for ADHD appears to be safe and well tolerated. Most of the adverse events reported in the randomised controlled trials are mild and transient. Decreased appetite, growth decrease and the impact on sleep (insomnia for stimulants and somnolence for alpha2-agonists) are among the most common events. Concerns exist about cardiovascular and psychiatric AEs, even if the available evidence does not support an association with medications. PMID- 28984473 TI - The continuing evolution of cardiac troponin I biomarker analysis: from protein to proteoform. AB - INTRODUCTION: The troponin complex consists of three proteins that fundamentally couple excitation with contraction. Circulating cardiac-specific Troponin I (cTnI) serves as diagnostic biomarker tools for risk stratification of acute coronary syndromes and acute myocardial infarction (MI). Within the heart, cTnI oscillates between inactive and active conformations to either block or disinhibit actinomyosin formation. This molecular mechanism is fine-tuned through extensive protein modifications whose profiles are maladaptively altered with co morbidities including hypertrophic cardiomyopathy, diabetes, and heart failure. Technological advances in analytical platforms over the last decade enable routine baseline cTnI analysis in patients without cardiovascular complications, and hold potential to expand cTnI readouts that include modified cTnI proteoforms. Areas covered: This review covers the current state, advances, and prospects of analytical platforms that now enable routine baseline cTnI analysis in patients. In parallel, improved mass spectrometry instrumentation and workflows already reveal an array of modified cTnI proteoforms with promising diagnostic implications. Expert commentary: New analytical capabilities provide clinicians and researchers with an opportunity to address important questions surrounding circulating cTnI in the improved diagnosis of specific patient cohorts. These techniques also hold considerable promise for new predictive and prescriptive applications for individualized profiling and improve patient care. PMID- 28984478 TI - PD-L1 in immune-escape of breast and prostate cancers: from biology to therapy. PMID- 28984479 TI - Comprehensive characterization of differentially expressed genes in thyroid cancer. AB - AIM: To explore the patterns of gene expression and functionally characterize the differentially expressed genes (DEGs) in thyroid cancer. METHODS: DEGs were determined between 57 paired thyroid cancer and noncancerous tissues using DESeq2. Subsequently, the main functions of the DEGs were studied by a variety of analyses. RESULTS: We identified a cohort of 752 upregulated and 309 downregulated DEGs in thyroid cancer. Several hub DEGs were found in the protein protein interaction networks. We also revealed a set of DEGs that were dysmethylated, involved in copy number variations and associated with clinical features in thyroid cancer. CONCLUSION: These results provide some novel findings on DEGs in thyroid cancer, which will be useful to guide further investigation and target therapy for this disease. [Formula: see text]. PMID- 28984480 TI - The current status of adjuvant treatment for high-risk renal cell carcinoma. PMID- 28984481 TI - Dynamic Functional Assessment of Hand Motion Using an Animation Glove: The Effect of Stenosing Tenosynovitis. AB - BACKGROUND: The aim of the present study is to determine whether an animation glove can be utilized to provide a reliable and reproducible assessment of dynamic hand function and whether this assessment is altered in the setting of hand pathology. METHODS: Ten subjects without known hand pathology and 11 subjects with known stenosing tenosynovitis were assessed on tasks involving hand function at varied speeds, including forceful and gradual making of a fist and the quick and slow grip of a baseball using an animation glove to record range of motion and measures of velocity (CyberGlove II). RESULTS: In normal subjects, peak extension and flexion velocity of the index and middle finger was highest in the metacarpophalangeal and lowest in the distal interphalangeal; however, the converse was true in the ring finger. In those subjects with stenosing tenosynovitis, the animation glove was able to detect a triggering event during assessment. Furthermore, there was a significant decrease in the maximum velocity of the proximal interphalangeal joint observed with the slow fist task in both flexion and extension (55%, P < .01) in the affected hand when compared with the unaffected hand. CONCLUSIONS: The CyberGlove II can be utilized in the dynamic functional analysis of the hand and is able to detect a triggering event in subjects with known stenosing tenosynovitis. Those subjects demonstrate a significant decrease in maximum velocity in slow fist tasks, highlighting the need for comprehensive assessment to ascertain the full extent of functional limitations that can occur in the setting of hand pathology. PMID- 28984482 TI - Public Library Staff as Community Health Partners: Training Program Design and Evaluation. AB - Public libraries are free and open to all-and accessed at high rates by vulnerable populations-which positions them to be key public health allies. However, library staff themselves often feel ill-equipped to address the health and social concerns of their patrons. To fill this gap, we developed a case-based training curriculum to help library staff recognize, engage, and refer vulnerable patrons to appropriate resources. Topics addressed in the training, including homelessness, mental health and substance use disorders, immigration, and trauma, were selected based on findings from a prior community needs assessment. Using a modified measure of self-efficacy, participants ( n = 33) were surveyed before and after each session. Several participants ( n = 7) were also interviewed 4 months after the training was completed. Overall, staff reported significant increases in comfort, confidence, and preparedness in assisting vulnerable patrons across all topic areas. Qualitative findings reflected positive perceived impact and value of the trainings. Staff felt training resources should be made more readily accessible. Improving library staff capacity to address the health and social needs of their patrons can further establish public libraries as partners in improving population health. PMID- 28984483 TI - Latest advances in adult gastrointestinal stromal tumors. AB - Gastrointestinal stromal tumors (GISTs) are the most common GI tract mesenchymal tumors. GIST patients are optimally managed by a precision medicine approach. Herein, we discuss the latest advances in precision medicine and ongoing clinical trials relevant to GIST. Circulating tumor DNA for detection of mutational changes could replace tissue biopsies and radiographic imaging once validated. Most GISTs are KIT/PDGFRalpha mutated, and despite the good clinical response to imatinib, treatment is generally not curative, more often due to secondary mutations. New mechanisms to bypass this resistance by inhibiting KIT downstream pathways and by targeting multiple KIT or PDGFRalpha mutations are being investigated. Immunotherapy for GIST patients is in its infancy. These approaches may lead to more effective, less toxic therapies. PMID- 28984484 TI - The perceptions of the causes of cardiac diseases: a taxonomy. AB - OBJECTIVE: This study verifies whether the open-ended question of the B-IPQ can collect causal attributions of patients with cardiac diseases, define the more frequent causal attributions reported, classify them and describe the relation between the classification of the causes and patients' characteristics. DESIGN: A group of 2011 patients with cardiac diseases was recruited during the first week of cardiac rehabilitation. PRIMARY OUTCOME MEASURES: Every participant filled in the B-IPQ and the HADS. The qualitative and quantitative analyses of the text using T-LAB identified the most frequent causal attributions and their co occurrences. RESULTS: Among the patients, 26% did not recognise any causal attribution. The likelihood that the patients did not provide an answer was increased in older patients, females, patients with lower levels of education and higher levels of depression. Smoking and stress emerged as the most important attributions, followed by genetics, metabolic syndrome, work and nutrition. Four thematic clusters were identified: 'work and stress', 'metabolic syndrome and hypertension', 'displeasures and body care' and 'heredity and other related diseases'. CONCLUSIONS: This study suggests a classification of the causal attributions in patients with cardiac diseases and identifies thematic patterns and unknown attributions. The themes identified can serve as categories for future closed-ended questions. PMID- 28984485 TI - Exercise-induced bronchospasm in a hot and dry region: study of asthmatic, rhinitistic and asymptomatic adolescents. AB - BACKGROUND: Exercise-induced bronchospasm (EIB) is the bronchial narrowing that occurs after intense exercise in a significant number of asthmatics and in some non-asthmatics. This study aims to evaluate the occurrence of EIB in adolescents with asthma, rhinitis and respiratory asymptomatics in a hot and dry climate. RESEARCH DESIGN AND METHODS: This is a cross-sectional study based on an epidemiological study that evaluated the prevalence of asthma in schoolchildren in a semi-arid zone of Brazil. The EIB was defined as a reduction in forced expiratory volume in first second (FEV1) greater than 10%. RESULTS: A total of 114 individuals participated in the study (36.8% male), of whom 54 were asymptomatic, 30 asthmatic and 30 with rhinitis. Asthmatics presented a higher proportion of EIB in comparison to rhinitis and asymptomatics (46.7% vs. 13.3% and 7.4%, p = 0.001) and none of the individuals had severe EIB (DeltaFEV1 >= 50%). CONCLUSIONS: A large proportion of the asthmatics selected from the community for the clinical study had EIB. Among participants with rhinitis, EIB was found in slightly more than 10%, while in the asymptomatics the frequency was slightly more than 5%. This study presents an important aspect in individuals living in hot and dry climates. PMID- 28984486 TI - Exergames vs. traditional exercise: investigating the influencing mechanism of platform effect on subthreshold depression among older adults. AB - OBJECTIVE: This study aimed to examine the influencing mechanism of exercise platform effect on subthreshold depression among older adults by comparing exergames and traditional exercise. METHOD: One hundred and two Singaporean older adults were assigned to either playing Wii exergames or performing traditional exercise programs once a week, for six weeks. RESULTS: Results confirmed a direct negative platform effect on subthreshold depression and further supported the mediation role of positive emotions in the platform effect. It implied that exergames led to higher positive emotions than traditional exercise, which further reduced the subthreshold depression among older adults. Self-efficacy was not supported to be a significant mediator in the relations between exercise platform and subthreshold depression. CONCLUSION: A better understanding of the mechanisms behind the antidepressant effects of exercise platform would not only provide additional insight into a possible causal association, but also inspire the future use of exergames in the treatment of subthreshold depression. PMID- 28984487 TI - Dapagliflozin and saxagliptin tablets for adults with type 2 diabetes. AB - INTRODUCTION: Saxagliptin (a dipeptidyl peptidase-4 inhibitor, DPP-4i) and dapagliflozin (a sodium-glucose cotransporter type 2 inhibitor, SGLT2i) improve glucose control in type 2 diabetes (T2D) through different potentially complementary mechanisms, thus offering the opportunity for a combined therapy. Area covered: The characteristics of the saxagliptin/dapagliflozin combination are analysed, focusing on: 1) pharmacokinetic and pharmacodynamic properties; 2) efficacy and safety in phase III trials with concurrent and sequential add-on therapy; and 3) potential use in clinical practice, including in special populations (cardiovascular disease, heart failure, chronic kidney disease, elderly). Expert commentary: Conclusions drawn from clinical trials investigating combination with the separate drugs are considered to apply to the fixed-dose combination (FDC) that demonstrates bioequivalence. Dual saxagliptin/dapagliflozin therapy is more potent than either monotherapy and can be used as an initial combination or a stepwise sequential approach. Dual therapy is generally well tolerated and may be used in special populations, with some limitations because of the presence of dapagliflozin. However, the latter may offer some advantages because of multiple effects attributed to SGLT2i. The best place of this dual combination for the management of T2D and the profile of patients who will make the most of this combined therapy remains to be defined. PMID- 28984488 TI - Prognostic impact of germline mutations in inherited cancer syndromes. PMID- 28984490 TI - Pitfalls in conducting prospective trials in stage III cardiac amyloidosis - experience from the REVEAL study. PMID- 28984489 TI - Directing the use of DDR kinase inhibitors in cancer treatment. AB - INTRODUCTION: Defects in the DNA damage response (DDR) drive the development of cancer by fostering DNA mutation but also provide cancer-specific vulnerabilities that can be exploited therapeutically. The recent approval of three different PARP inhibitors for the treatment of ovarian cancer provides the impetus for further developing targeted inhibitors of many of the kinases involved in the DDR, including inhibitors of ATR, ATM, CHEK1, CHEK2, DNAPK and WEE1. Areas covered: We summarise the current stage of development of these novel DDR kinase inhibitors, and describe which predictive biomarkers might be exploited to direct their clinical use. Expert opinion: Novel DDR inhibitors present promising candidates in cancer treatment and have the potential to elicit synthetic lethal effects. In order to fully exploit their potential and maximize their utility, identifying highly penetrant predictive biomarkers of single agent and combinatorial DDR inhibitor sensitivity are critical. Identifying the optimal drug combination regimens that could used with DDR inhibitors is also a key objective. PMID- 28984491 TI - Monitoring for antidepressant-associated adverse events in the treatment of patients with major depressive disorder: An international consensus statement. AB - OBJECTIVES: These recommendations were designed to ensure safety for patients with major depressive disorder (MDD) and to aid monitoring and management of adverse effects during treatment with approved antidepressant medications. The recommendations aim to inform prescribers about both the risks associated with these treatments and approaches for mitigating such risks. METHODS: Expert contributors were sought internationally by contacting representatives of key stakeholder professional societies in the treatment of MDD (ASBDD, CANMAT, WFSBP and ISAD). The manuscript was drafted through iterative editing to ensure consensus. RESULTS: Adequate risk assessment prior to commencing pharmacotherapy, and safety monitoring during pharmacotherapy are essential to mitigate adverse events, optimise the benefits of treatment, and detect and assess adverse events when they occur. Risk factors for pharmacotherapy vary with individual patient characteristics and medication regimens. Risk factors for each patient need to be carefully assessed prior to initiating pharmacotherapy, and appropriate individualised treatment choices need to be selected. Some antidepressants are associated with specific safety concerns which were addressed. CONCLUSIONS: Risks of adverse outcomes with antidepressant treatment can be managed through appropriate assessment and monitoring to improve the risk benefit ratio and improve clinical outcomes. PMID- 28984492 TI - Prognostic factors affecting survival after whole brain radiotherapy in patients with brain metastasized lung cancer. AB - BACKGROUND: Whole-brain radiotherapy (WBRT) has been the standard of care for multiple NSCLC brain metastases but due to its toxicity and lack of survival benefit, its use in the palliative setting is being questioned. PATIENT AND METHODS: This was a single institution cohort study including brain metastasized lung cancer patients who received WBRT at Karolinska University Hospital. Information about Recursive Partitioning Analysis (RPA) and Graded Prognostic Assessment (GPA) scores, demographics, histopathological results and received oncological therapy were collected. Predictors of overall survival (OS) from the time of received WBRT were identified by Cox regression analyses. OS between GPA and RPA classes were compared by pairwise log rank test. A subgroup OS analysis was performed stratified by RPA class. RESULTS: The cohort consisted of 280 patients. RPA 1 and 2 classes had better OS compared to class 3, patients with GPA <1.5 points had better OS compared to GPA>= 1.5 points and age >70 years was associated with worse OS (p< .0001 for all comparisons). In RPA class 2 subgroup analysis GPA >=1.5 points, age <=70 years and CNS surgery before salvage WBRT were independent positive prognostic factors. CONCLUSIONS: RPA class 3 patients should not receive WBRT, whereas RPA class 1 patients should receive WBRT if clinically indicated. RPA class 2 patients with age <=70 years and GPA >=1.5 points should be treated as RPA 1. WBRT should be omitted in RPA 2 patients with age >70. In RPA 2 patients with age <=70 years and GPA <1.5 points WBRT could be a reasonable option. PMID- 28984493 TI - Integration of tuberculosis and HIV services: Exploring the perspectives of co infected patients in Ghana. AB - Scaling up of integrated tuberculosis (TB)-human immunodeficiency virus (HIV) services remains sub-optimal in many resource-limited countries, including Ghana, where the two conditions take a heavy toll on the financial resources of health systems as well as infected persons. Previous studies have documented several implementation challenges towards TB-HIV service integration, but views of patients on integrated service delivery have not received commensurate research attention. This paper explored the experiences of 40 TB-HIV co-infected patients at different stages of treatment in Ghana. Using Normalisation Process Theory as a framework, data were coded using inter-rater coding technique and analysed inductively and deductively with the help of QSR NVivo 10. For several participants, either of the diseases was diagnosed 'accidentally', leading to inconsistencies in co-therapy administration, constraints regarding separate clinic appointment dates for TB and HIV and prolonged TB treatment due to treatment failure. Put differently, there were widespread negative experiences among TB-HIV co-infected patients with regard to treatment and care, especially among patients who were accessing care in separate facilities or separate units in the same facility. Co-infected patients unanimously support full-service integration. However, they felt powerless to request for reforms on a mode of service delivery. PMID- 28984494 TI - Binding of acarbose, an anti-diabetic drug to lysozyme: a combined structural and thermodynamic study. PMID- 28984495 TI - Dietary fatty acids modulation of human colon cancer cells: mechanisms and future perspectives. AB - Colorectal cancer (CRC) is one of the most common malignancies worldwide and its pathogenesis is proven to be related with dietary patterns, namely dietary fatty acid (FA) intake. We reviewed the evidences regarding the effect of different dietary FAs on human CRC cell lines proliferation and apoptosis. Altogether, the results obtained from in vitro studies show that monounsaturated FAs lack evidence regarding both proliferation and apoptosis, whereas there is a consensus about the anti-proliferative and pro-apoptotic effects, involving different intracellular targets, of n-3 polyunsaturated FAs, while n-6 series show a similar effect or no effects. The response to these dietary components depends on the cell type as well as the amount and duration of exposure. These results highlight the importance of identifying molecular targets for dietary components aiming to interfere with one of the main risk factors related with CRC incidence and prevalence. PMID- 28984496 TI - Spending Carveouts Substantially Improve the Accuracy of Performance Measurement in Shared Savings Arrangements: Findings From Simulation Analysis of Medicaid ACOs. AB - Accuracy of spending-based provider performance metrics is limited by random variation and components of spending that are uncontrollable by providers. Such components vary according to the care management focus and operational maturity of each provider group. This study uses data from New Jersey Medicaid accountable care organizations (ACOs) to examine how carving out uncontrollable components of spending affects the accuracy of performance measures in shared savings arrangements. Spending on injury care, custodial care in facilities (CCF), and amounts above $100 000 per patient are used as examples of potentially uncontrollable spending. Data from 7 applicant Medicaid ACOs are used to conduct Monte Carlo simulations examining the effects of carving out each type of uncontrollable spending under the assumption that controllable spending is reduced by 5%. The simulations show that failure to carve out uncontrollable injury care spending adds -3 to +1 percentage points of bias to the measurement of the true average savings rate (ASR) of 5% and can increase mean squared error (MSE) by a factor of up to 3. Failure to carve out uncontrollable CCF spending generates bias ranging from -4 to +9 percentage points and increases MSE by factors of 8 or more. Failure to carve out uncontrollable spending above $100 000 per person generates bias ranging from -5 to +5 percentage points and increases MSE by factors of 13 or more. Compared with the main modeling reported above, sensitivity analyses find even greater distortions in measured performance when uncontrollable spending is not carved out of the ASR calculation. PMID- 28984497 TI - Redefining ADHD Using an Adult Population: Should Inattention be Viewed as a Separate Dimension From Cognitive and Physiological Activity Level? AB - OBJECTIVE: The purpose of this study was to reexamine the latent structure of ADHD and sluggish cognitive tempo (SCT) due to issues with construct validity. Two proposed changes to the construct include viewing hyperactivity and sluggishness (hypoactivity) as a single continuum of activity level, and viewing inattention as a separate dimension from activity level. METHOD: Data were collected from 1,398 adults using Amazon's MTurk. A new scale measuring activity level was developed, and scores of Inattention were regressed onto scores of Activity Level using curvilinear regression. RESULTS: The Activity Level scale showed acceptable levels of internal consistency, normality, and unimodality. Curvilinear regression indicates that a quadratic (curvilinear) model accurately explains a small but significant portion of the variance in levels of inattention. CONCLUSION: Hyperactivity and hypoactivity may be viewed as a continuum, rather than separate disorders. Inattention may have a U-shaped relationship with activity level. Linear analyses may be insufficient and inaccurate for studying ADHD. PMID- 28984498 TI - Brilliant blue R dye is capable of suppressing amyloid fibril formation of lysozyme. AB - Amyloid fibril formation is associated with an array of degenerative diseases. While no real cure is currently available, evidence suggests that suppression of amyloid fibrillogenesis is an effective strategy toward combating these diseases. Brilliant blue R (BBR), a disulfonated triphenylmethane compound, has been shown to interact with fibril-forming proteins but exert different effects on amyloid fibrillogenesis. These inconsistent findings prompted us to further evaluate BBR's effect on the inhibition/suppresion of protein fibrillogenesis. Using 129 residue hen lysozyme, which shares high sequence homology to human lysozyme associated with hereditary non-neuropathic systemic amyloidosis, as a model, this study is aimed at thoroughly examining the influence of BBR on the in vitro protein fibrillogenesis. We first showed that BBR dose-dependently attenuated lysozyme fibril formation probably by affecting the fibril growth rate, with the value of IC50 determined to be ~4.39 MUM. Next, we employed tryptophan fluorescence quenching method to determine the binding constant and number of binding site(s) associated with BBR-lysozyme binding. In addition, we further conducted molecular docking studies to gain a better understanding of the possible binding site(s) and interaction(s) between lysozyme and BBR. We believe some of the information and/or knowledge concerning the structure-function relationship associated with BBR's suppressing activity obtained here can be applied for the future work in the subject matter related with the therapeutic strategies for amyloid diseases. PMID- 28984499 TI - The assessment of mindfulness skills: the "what" and the "how". AB - BACKGROUND: The five facets mindfulness questionnaire-short form (FFMQ-SF) is a new, brief measure for the assessment of mindfulness skills in clinical and nonclinical samples. The construct validity of the FFMQ-SF has not been previously assessed in community samples. AIMS: The present study investigated the factor structure of the Italian version of the FFMQ-SF. METHOD: Structured equation modeling was used to test the fit of three alternative models in a sample of highly educated adults (n = 211). RESULTS: A hierarchical model with a single second-order factor loaded by observing, describing, and acting with awareness (i.e. the mindfulness "what" skills) performed slightly better than both a five-factor model with correlated factors and a hierarchical model with a general second-order factor. The FFMQ-SF scores were significantly higher than those reported in both Dutch depressed patients and Australian undergraduate students for all facets (but nonreactivity for the Australian sample). CONCLUSIONS: Data support the multifaceted nature of mindfulness skills. Because of its brevity and simplicity of use, the FFMQ-SF is a promising questionnaire in longitudinal and clinical research. This questionnaire can serve as a guideline to help clinicians assess and monitor mindfulness skills acquisition, strengthening, and generalization, and prioritize mindfulness skills that need immediate attention. PMID- 28984500 TI - Ursolic acid and carvacrol may be potential inhibitors of dormancy protein small heat shock protein16.3 of Mycobacterium tuberculosis. AB - Small heat shock protein16.3 (sHSP16.3) is a crucial protein for survival of Mycobacterium tuberculosis (MTB) in its host. Besides, this protein acts as a molecular chaperone during stress and is indispensable for MTB's growth, virulence and cell-wall thickening. sHSP16.3 is also a promising candidate for vaccine, serodiagnosis and drug design as well. In the present study, we have targeted sHSP16.3 with two phytochemicals, namely ursolic acid and carvacrol using in silico approach. Molecular docking analysis showed that both phytochemicals (ursolic acid and carvacrol) have docked with sHSP16.3 and shown tendency to inhibit the function of this vital protein of MTB. In addition, both compounds have exhibited strong compatibility with sHSP16.3 during whole 60 ns duration of molecular dynamics simulation. Further, the molecular mechanic/generalized Born/Poisson-Boltzmann surface area (MM/G/P/BSA) free energies were calculated which showed that both phytocompounds have stable and favourable binding energies causing strong binding with binding site of sHSP16.3. Taking together, the data of present study suggest that both phytocompounds may be potential inhibitor of sHSP16.3 of MTB and a best alternative to standard anti tuberculosis drugs. PMID- 28984501 TI - Response to: Small group activities within academic communities improve the connectedness of students and faculty. PMID- 28984502 TI - The association between hypogonadism symptoms with serum testosterone, FSH and LH in men. AB - OBJECTIVES: This study aimed to determine the relationship of hypogonadism symptoms with the levels of sex hormones in men. METHODS: This cross-sectional study was conducted on 140 men aged above 40 years. Data collections were conducted by Aging Male Scales (AMS) questionnaire and some sociodemographic variables. Then, 3 ml blood serum was sampled for testosterone (free and total), FSH and LH. Data were analyzed by descriptive and analytical statistics. RESULTS: Mean age score was 52.09 +/- 7.096. There was no significant association between total score of the symptoms of hypogonadism and serum total and free testosterone level while it was shown significant association with BMI (p = .021) and occupation (p = .005). CONCLUSION: The most men experienced the symptoms of hypogonadism and the majority of the symptoms were related to psychological domain. The symptoms of hypogonadism are considered to some factors like BMI and occupation too. PMID- 28984503 TI - Temporal dynamics of anxiety-related attentional bias: is affective context a missing piece of the puzzle? AB - Previous research has demonstrated that anxious individuals attend to negative emotional information at the expense of other information. This is commonly referred to as attentional bias. The field has historically conceived of this process as relatively static; however, research by [Zvielli, A., Bernstein, A., & Koster, E. H. W. (2014). Dynamics of attentional bias to threat in anxious adults: Bias towards and/or away? PLoS ONE, 9(8), e104025; Zvielli, A., Bernstein, A., & Koster, E. H. W. (2015). Temporal dynamics of attentional bias. Clinical Psychological Science, 3(5), 772-788.], and others, challenges this assumption by demonstrating considerable temporal variability in attentional bias amongst anxious individuals. Still, the mechanisms driving these temporal dynamics are less well known. Using a modified dot-probe task, the present study examined the impact of two relevant contextual variables- affective valence and trial repetition. Affective context was instantiated by the presentation of negative versus neutral pictures before each trial, while repetition context was achieved via the presentation of the valenced pictures in either a blocked- or mixed-trial design. Results indicate that individuals with higher trait-anxiety levels were significantly more influenced by blocked presentations of negative affective information, leading to greater temporal fluctuations in attentional bias. Furthermore, our findings provide additional evidence that attentional bias is best conceptualised as dynamic and variable, and that an individual's affective experience is one factor that regulates attentional bias dynamics. Implications relating to theoretical and methodological factors are discussed. PMID- 28984504 TI - Comment on: Long-term benefits by a mind-body medicine skills course on perceived stress and empathy among medical and nursing students. PMID- 28984505 TI - Strain-controlled fatigue behaviors of porous PLA-based scaffolds by 3D-printing technology. AB - In the study, the low-cycle fatigue behaviors of 3D-printed poly lactic acid (PLA) scaffolds with 60% porosity and two kinds of geometrical pores were investigated under strain-controlled loading. The obtained Deltaepsilona-Nf curves were fitted by Coffin-Manson relation. The mechanical stability of the porous structure under cyclic loading was studied. Both kinds of specimens undergo the strain softening after the initial cyclic hardening. The scaffold with circular pore exhibits stable resistance to the fatigue damage which is desirable for bone repairing. Regarding to the accumulation of inelastic deformation, the triangular-scaffold is more sensitive to the cyclic load. The superior fatigue behaviors of the scaffold with circular pore is attributed to homogeneous distribution of the applied mechanical stress and diminishing stress concentration by the introduction of circular pore. PMID- 28984506 TI - Manipulating affective state influences conditioned appetitive responses. AB - Affective states influence how individuals process information and behave. Some theories predict emotional congruency effects (e.g. preferential processing of negative information in negative affective states). Emotional congruency should theoretically obstruct the learning of reward associations (appetitive learning) and their ability to guide behaviour under negative mood. Two studies tested the effects of the induction of a negative affective state on appetitive Pavlovian learning, in which neutral stimuli were associated with chocolate (Experiment 1) or alcohol (Experiment 2) rewards. In both experiments, participants showed enhanced approach tendencies towards predictors of reward after a negative relative to a positive performance feedback manipulation. This increase was related to a reduction in positive affect in Experiment 1 only. No effects of the manipulation on conditioned reward expectancies, craving, or consumption were observed. Overall, our findings support the idea of counter-regulation, rather than emotional congruency effects. Negative affective states might therefore serve as a vulnerability factor for addiction, through increasing conditioned approach tendencies. PMID- 28984508 TI - Subjective, physiological, and behavioural responses towards evaluatively conditioned stimuli. AB - Evaluative Conditioning (EC) is commonly defined as the change in liking of a stimulus (conditioned stimulus, CS) due to its pairings with an affective unconditioned stimulus (US). In Experiment 1, we investigated effects of repeated stimulus pairings on affective responses, i.e. valence and arousal ratings, pupil size, and duration estimation. After repeatedly pairing the CSs with affective USs, a consistent pattern of affective responses emerged: The CSnegative was rated as being more negative and more arousing, resulted in larger pupils, and was temporally overestimated compared to the CSneutral. In Experiment 2, the influence of a mere instruction about the contingency between a CS and US on affective responses was examined. After mere instruction about upcoming pairings between the CS and US, subjective ratings also changed, but there was neither evidence for differential pupillary responses nor for differential temporal processing. The results indicate that EC via pairings or instructions can change the affective responses towards formerly neutral stimuli and introduce pupil size as a physiological measure in EC research. However, Experiment 2 suggests that there might be moderating factors based on the type of EC procedure involved. PMID- 28984507 TI - Anterior or posterior walkers for children with cerebral palsy? A systematic review. AB - OBJECTIVE: To review the literature comparing use of anterior and posterior walkers (PW's) by children with cerebral palsy (CP) to determine which walker type is preferable. METHODS: Electronic databases were searched using pre-defined terms by two independent reviewers. Reference lists of included studies were hand searched. Studies published between 1985 and 2016 comparing use of anterior and PW's by children with CP were included. All study designs and outcomes were accepted. Risk of bias was assessed using the "Quality assessment standard for a cross-over study". Quality of evidence was evaluated using GRADE. RESULTS: Six studies were analysed. All studies had small sample sizes. A total of 4/6 studies were randomized. A total of 4/6 had high risk of bias. Outcomes included velocity, pelvic tilt, hip flexion, knee flexion, step length, stride length, cadence, double stance time, oxygen cost and participant/parental preference. Velocity, trunk flexion/pelvic tilt, and stability may be improved by using a PW, however, GRADE quality was very low for all outcomes and there was heterogeneity between studies. The majority of participants and parents preferred the PW. CONCLUSIONS: Heterogeneity and low quality of existing evidence prevented recommendation of one walker type. Well-designed studies with adequate power are needed to inform clinical recommendations. Implications for rehabilitation Clinical recommendations cannot be made for whether anterior or posterior walkers are preferable for children with cerebral palsy based on the existing evidence. Velocity, trunk flexion/pelvic tilt, and stability may be improved by using a posterior walker. The majority of walking aid users and their parents preferred posterior walkers. Adequately powered studies designed to minimize bias are needed. PMID- 28984509 TI - Asking About Pets Enhances Patient Communication and Care: A Pilot Study. AB - This research explored whether asking patients about their pets would enable better environmental/social history taking, and improve patient communication/care. Primary health care providers (PHPs) were surveyed about prevalence of patients living with pets, the health impact of pets, and influences on patient communication. Following an educational intervention, they committed to asking patients about their pets. A follow-up survey was conducted electronically. PHPs were recruited at a continuing medical education (CME) conference and at CME workshops. All 225 participants were PHPs. At the conference, participants were educated one-on-one about the clinical relevance of pets in the family. CME sessions were large or small group teaching. Baseline and final surveys measured awareness of pets in patients' families, assessment of determinants of health, impact on rapport with patients, and patient care. A sign test assessed difference in scores using repeated-measures analysis. Binomial outcomes were assessed using Fisher's exact test. Comments were themed. Ninety four PHPs (42%) completed the study. Pet-related discussions opened communication with patients. Two-thirds of participants identified positive effects on practice and on relationships with patients. PHPs were able to leverage the health benefits of pets (zooeyia) and mitigate zoonotic risk. Asking patients about pets in the family reveals clinically relevant information, improves communication, and strengthens the therapeutic alliance. PMID- 28984510 TI - Psychometric evaluation of the hope, agency and opportunity (HAO); a brief measure of mental health recovery. AB - BACKGROUND: The development of safe and effective mental health services is a priority. This requires valid measures of personal recovery, yet these tools are not embedded in routine clinical practice. Brief "patient reported measures" are most likely to be acceptable to service-users and clinicians. The 4-item "Hope, Agency and Opportunity" (HAO) was co-produced to assess recovery outcomes and experience of mental health services. AIM: To evaluate the psychometric properties of the HAO. METHOD: A clinical sample from secondary healthcare services and a non-clinical sample were assessed at baseline and two weeks, on measures of personal recovery. RESULTS: Factor analysis indicated goodness of fit for the HAO with both clinical and non-clinical samples. The measure demonstrated acceptable internal consistency, moderate to strong construct validity and substantial test-retest reliability over two weeks. CONCLUSIONS: The HAO demonstrates satisfactory psychometric properties. Co-production of the measure confers clinical credibility. The brevity of the tool means it can be incorporated into routine clinical practice to drive improvements in service quality. PMID- 28984511 TI - Interbody distraction and vertebral body reconstruction with polymethylmethacrylate for the treatment of pathological fractures. AB - OBJECTIVE Treatment of epidural spinal cord compression (ESCC) caused by tumor includes surgical decompression and stabilization followed by postoperative radiation. In the case of severe axial loading impairment, anterior column reconstruction is indicated. The authors describe the use of interbody distraction to restore vertebral body height and correct kyphotic angulation prior to reconstruction with polymethylmethacrylate (PMMA), and report the long term durability of such reconstruction. METHODS A single institution, prospective series of patients with ESCC undergoing single-stage decompression, anterior column reconstruction, and posterior instrumentation from 2013 to 2016 was retrospectively analyzed. Several demographic, perioperative, and radiographic measurements were collected. Descriptive statistics were compiled, in addition to postoperative changes in anterior height, posterior height, and kyphosis. Paired Student t-tests were performed for each variable. Overall survival was calculated using the techniques described by Kaplan and Meier. RESULTS Twenty-one patients underwent single-stage posterior decompression with interbody distraction and anterior column reconstruction using PMMA. The median age and Karnofsky Performance Scale score were 61 years and 70, respectively. Primary tumors included renal cell (n = 8), lung (n = 4), multiple myeloma (n = 2), prostate (n = 2), and other (n = 5). Eighteen patients underwent a single-level vertebral body reconstruction and 3 underwent multilevel transpedicular corpectomies. The median survival duration was 13.3 months. In the immediate postoperative setting, statistically significant improvement was noted in anterior body height (p = 0.0017, 95% confidence interval [CI] -4.15 to -1.11) and posterior body height (p = 0.0116, 95% CI -3.14 to -0.45) in all patients, and improved kyphosis was observed in those with oblique endplates (p = 0.0002, 95% CI 11.16-20.27). In the median follow-up duration of 13.9 months, the authors observed 3 cases of asymptomatic PMMA subsidence. One patient required reoperation in the form of extension of fusion. CONCLUSIONS In situ interbody distraction allows safe and durable reconstruction with PMMA, restores vertebral height, and corrects kyphotic deformities associated with severe pathological fractures caused by tumor. This is accomplished with minimal manipulation of the thecal sac and avoiding an extensive 360 degrees surgical approach in patients who cannot tolerate extensive surgery. PMID- 28984512 TI - Spinal cord injury after traumatic spine fracture in patients with ankylosing spinal disorders. AB - OBJECTIVE Spinal cord injury (SCI) is a major complication of spinal fractures in patients with ankylosing spondylitis (AS) and diffuse idiopathic skeletal hyperostosis (DISH). Due to the uncommon nature of these conditions, existing literature consists of relatively small case series without detailed neurological data. This study aims to investigate the incidence, predictors, and sequelae of SCI in patients with a traumatic fracture of the ankylosed spine. METHODS The study included all patients older than 18 years of age with AS or DISH who presented to two affiliated tertiary care centers between January 1, 1990, and January 1, 2016, and had a traumatic fracture of the spine. Factors associated with SCI after traumatic fracture were compared using Fisher's exact tests. Logistic regression was used for the analysis of predictive factors for SCI. For the comparison of probability of survival between patients with and without SCI, Kaplan-Meier methodology was used. RESULTS One hundred seventy-two patients with a traumatic fracture of an ankylosed spine were included. Fifty-seven patients (34.1%) had an SCI associated with the fracture. The cervical spine was the most fractured region for patients both with (77.2%) and without (51.4%) SCI. A cervical fracture (odds ratio [OR] 2.70, p = 0.024) and a spinal epidural hematoma (SEH) after fracture (OR 2.69, p = 0.013) were predictive of SCI. Eleven patients (19.3%) with SCI had delayed SCI (range 8-230 days). Of 44 patients with SCI and sufficient follow-up, 20 (45.5%) had neurological improvement after treatment. Early and late complication rates were significantly higher (p = 0.001 and p = 0.004) and hospital stay was significantly longer (p = 0.001) in patients with SCI. The probability of survival was significantly lower in the SCI group compared with the non-SCI group (p = 0.006). CONCLUSIONS The incidence of SCI was high after fracture of the spine in patients with AS and DISH. Predictive factors for SCI after fracture were a fracture in the cervical spine and an SEH following fracture. One-fifth of the patients with SCI had delayed SCI. Patients with SCI had more complications, a longer hospital stay, and a lower probability of survival. Less than half of the patients with SCI showed neurological improvement. PMID- 28984513 TI - Fascicular shifting: a novel technique to overcome large nerve defects. AB - OBJECTIVE Over the last decade, a number of authors have investigated the utility of different biological and synthetic matrices as alternatives to conventional nerve grafts. However, the autologous nerve graft remains the gold standard, even though it often involves using a pure sensory nerve to reconstruct a mixed or even a pure motor nerve. Furthermore, limited donor sites often necessitate a significant mismatch of needed nerve tissue, especially for large proximal nerve defects such as brachial plexus lesions. Here, the authors present a new technique that overcomes these problems: the fascicular shift procedure (FSP). A fascicular group of the nerve distal to the injury is harvested in a sufficient length to bridge the nerve defect. METHODS The method of fascicular shifting was tested at the sciatic nerve in 45 Lewis rats. In the experimental group, a 15-mm nerve defect was created and reconstructed with a fascicular group that was harvested directly distal to the gap. This group was compared with 1 negative control group (defect without reconstruction) and 3 positive control groups (sensory, motor, and mixed graft). After 12 weeks of nerve regeneration, outcome was evaluated using retrograde labeling, histomorphometric analysis, and muscle force analysis. RESULTS All reconstructed groups showed successful regeneration with various levels of function. The negative control group showed minimal force measurements that were of no functional value. The fascicular shift provided sufficient guidance to overcome nerve defects, had higher (p < 0.1) motor neuron counts (1958.75 +/- 657.21) than the sensory graft (1263.50 +/- 538.90), and was equal to motor grafts (1490.43 +/- 794.80) and mixed grafts (1720.00 +/- 866.421). This tendency of improved motor regeneration was confirmed in all analyses. The mixed graft group was compared with the experimental group to investigate the influence of the potential damage induced by the fascicular shift distal to the repair site. However, none of the analyses revealed an impairment of nerve regeneration for both the tibial and common peroneal index muscles. CONCLUSIONS This study demonstrates that harvesting a transplant from the nerve segment distal to the injury site offers a mixed graft without causing additional donor-site morbidity. These grafts perform statistically better than a standard sensory graft in terms of motor recovery. The fascicular shift presents a novel method to reconstruct large proximal nerve defects, making it immensely attractive in brachial plexus reconstruction. PMID- 28984514 TI - Inpatient costs and blood transfusion rates of sarcopenic patients following thoracolumbar spine surgery. AB - OBJECTIVE Sarcopenia, the muscle atrophy associated with aging and disease progression, accounts for nearly $18.5 billion in health care expenditures annually. Given the high prevalence of sarcopenia in patients undergoing orthopedic surgery, the goal of this study was to assess the impact of sarcopenia on inpatient costs following thoracolumbar spine surgery. METHODS Patients older than 55 years undergoing thoracolumbar spine surgery from 2003 to 2015 were retrospectively analyzed. Sarcopenia was measured using total psoas area at the L 4 vertebra on perioperative CT scans. Hospital billing data were used to compare inpatient costs, transfusion rate, and rate of advanced imaging utilization. RESULTS Of the 50 patients assessed, 16 were sarcopenic. Mean total hospital costs were 1.75-fold greater for sarcopenic patients compared with nonsarcopenic patients ($53,128 vs $30,292, p = 0.04). Sarcopenic patients were 2.1 times as likely to require a blood transfusion (43.8% vs 20.6%, p = 0.04). Sarcopenic patients had a 2.6-fold greater usage of advanced imaging (68.8% vs 26.5%, p = 0.002) with associated higher diagnostic imaging costs ($2452 vs $801, p = 0.01). Sarcopenic patients also had greater pharmacy, laboratory, respiratory care, and emergency department costs. CONCLUSIONS This study is the first to show that sarcopenia is associated with higher postoperative costs and rates of blood transfusion following thoracolumbar spine surgery. Measuring the psoas area may represent a strategy for predicting perioperative costs in spine surgery patients. PMID- 28984515 TI - Surgical timing for cervical and upper thoracic injuries in patients with polytrauma. AB - OBJECTIVE Few studies have investigated the advantages of early spinal stabilization in the patient with polytrauma in terms of reduction of morbidity and mortality. Previous analyses have shown that early stabilization may reduce ICU stay, with no effect on complication rates. METHODS The authors prospectively observed 340 polytrauma patients with an Injury Severity Score (ISS) of greater than 16 at a single Level 1 trauma center who were treated in accordance with a protocol termed "early appropriate care," which emphasizes operative treatment of various fractures within 36 hours of injury. Of these patients, 46 had upper thoracic and/or cervical spine injuries. The authors retrospectively compared patients treated according to protocol versus those who were not. Continuous variables were compared using independent t-tests and categorical variables using Fisher's exact test. Logistic regression analysis was performed to account for baseline confounding factors. RESULTS Fourteen of 46 patients (30%) did not undergo surgery within 36 hours. These patients were significantly more likely to be older than those in the protocol group (53 vs 38 years, p = 0.008) and have greater body mass index (BMI; 33 vs 27, p = 0.02), and they were less likely to have a spinal cord injury (SCI) (82% did not have an SCI vs 44% in the protocol group, p = 0.04). In terms of outcomes, patients in the protocol-breach group had significantly more total ventilator days (13 vs 6 days, p = 0.02) and total ICU days (16 vs 9 days, p = 0.03). Infection rates were 14% in the protocol-breach group and 3% in the protocol group (p = 0.2) Total complications trended toward being statistically significantly more common in the protocol-breach group (57% vs 31%). After controlling for potential confounding variables by logistic regression (including age, sex, BMI, race, and SCI), total complications were significantly (p < 0.05) greater in the protocol-breach group (OR 29, 95% CI 1.9 1828). This indicates that the odds of developing "any complication" were 29 times greater if treatment was delayed more than 36 hours. CONCLUSIONS Early surgical stabilization in the polytrauma patient with a cervical or upper thoracic spine injury is associated with fewer complications and improved outcomes. Hospitals may consider the benefit of protocols that promote early stabilization in this patient population. PMID- 28984516 TI - Multilevel, ultra-large-volume epidural blood patch for the treatment of neurocognitive decline associated with spontaneous intracranial hypotension: case report. AB - Spontaneous intracranial hypotension (SIH) is a progressive clinical syndrome characterized by orthostatic headaches, nausea, emesis, and occasionally focal neurological deficits. Rarely, SIH is associated with neurocognitive changes. An epidural blood patch (EBP) is commonly used to treat SIH when conservative measures are inadequate, although some patients require multiple EBP procedures or do not respond at all. Recently, the use of a large-volume (LV) EBP has been described to treat occult leak sites in treatment-refractory SIH. This article describes the management of a patient with profound neurocognitive decline associated with SIH, who was refractory to conservative management and multiple interventions. The authors describe the successful use of an ultra-LV-EBP of 120 ml across multiple levels, the largest volume reported in the literature, and describe the technical aspects of the procedure. This procedure has resulted in dramatic and sustained symptom resolution. PMID- 28984518 TI - Validation of the unruptured intracranial aneurysm treatment score: comparison with real-world cerebrovascular practice. AB - OBJECTIVE The purpose of this study was to compare the unruptured intracranial aneurysm treatment score (UIATS) recommendations with the real-world experience in a quaternary academic medical center with a high volume of patients with unruptured intracranial aneurysms (UIAs). METHODS All patients with UIAs evaluated during a 3-year period were included. All factors included in the UIATS were abstracted, and patients were scored using the UIATS. Patients were categorized in a contingency table assessing UIATS recommendation versus real world treatment decision. The authors calculated the percentage of misclassification, sensitivity, specificity, and area under the receiver operating characteristic (ROC) curve. RESULTS A total of 221 consecutive patients with UIAs met the inclusion criteria: 69 (31%) patients underwent treatment and 152 (69%) did not. Fifty-nine (27%) patients had a UIATS between -2 and 2, which does not offer a treatment recommendation, leaving 162 (73%) patients with a UIATS treatment recommendation. The UIATS was significantly associated with treatment (p < 0.001); however, the sensitivity, specificity, and percentage of misclassification were 49%, 80%, and 28%, respectively. Notably, 51% of patients for whom treatment would be recommended by the UIATS did not undergo treatment in the real-world cohort and 20% of patients for whom conservative management would be recommended by UIATS had intervention. The area under the ROC curve was 0.646. CONCLUSIONS Compared with the authors' experience, the UIATS recommended overtreatment of UIAs. Although the UIATS could be used as a screening tool, individualized treatment recommendations based on consultation with a cerebrovascular specialist are necessary. Further validation with longitudinal data on rupture rates of UIAs is needed before widespread use. PMID- 28984517 TI - Intermediate-risk meningioma: initial outcomes from NRG Oncology RTOG 0539. AB - OBJECTIVE This is the first clinical outcomes report of NRG Oncology RTOG 0539, detailing the primary endpoint, 3-year progression-free survival (PFS), compared with a predefined historical control for intermediate-risk meningioma, and secondarily evaluating overall survival (OS), local failure, and prospectively scored adverse events (AEs). METHODS NRG Oncology RTOG 0539 was a Phase II clinical trial allocating meningioma patients to 1 of 3 prognostic groups and management strategies according to WHO grade, recurrence status, and resection extent. For the intermediate-risk group (Group 2), eligible patients had either newly diagnosed WHO Grade II meningioma that had been treated with gross-total resection (GTR; Simpson Grades I-III) or recurrent WHO Grade I meningioma with any resection extent. Pathology and imaging were centrally reviewed. Patients were treated with radiation therapy (RT), either intensity modulated (IMRT) or 3D conformal (3DCRT), 54 Gy in 30 fractions. The RT target volume was defined as the tumor bed and any nodular enhancement (e.g., in patients with recurrent WHO Grade I tumors) with a minimum 8-mm and maximum 15-mm margin, depending on tumor location and setup reproducibility of the RT method. The primary endpoint was 3 year PFS. Results were compared with historical controls (3-year PFS: 70% following GTR alone and 90% with GTR + RT). AEs were scored using NCI Common Toxicity Criteria. RESULTS Fifty-six patients enrolled in the intermediate-risk group, of whom 3 were ineligible and 1 did not receive RT. Of the 52 patients who received protocol therapy, 4 withdrew without a recurrence before 3 years leaving 48 patients evaluable for the primary endpoint, 3-year PFS, which was actuarially 93.8% (p = 0.0003). Within 3 years, 3 patients experienced events affecting PFS: 1 patient with a WHO Grade II tumor died of the disease, 1 patient with a WHO Grade II tumor had disease progression but remained alive, and 1 patient with recurrent WHO Grade I meningioma died of undetermined cause without tumor progression. The 3-year actuarial local failure rate was 4.1%, and the 3-year OS rate was 96%. After 3 years, progression occurred in 2 additional patients: 1 patient with recurrent WHO Grade I meningioma and 1 patient with WHO Grade II disease; both remain alive. Among 52 evaluable patients who received protocol treatment, 36 (69.2%) had WHO Grade II tumors and underwent GTR, and 16 (30.8%) had recurrent WHO Grade I tumors. There was no significant difference in PFS between these subgroups (p = 0.52, HR 0.56, 95% CI 0.09-3.35), validating their consolidation. Of the 52 evaluable patients, 44 (84.6%) received IMRT, and 50 (96.2%) were treated per protocol or with acceptable variation. AEs (definitely, probably, or possibly related to protocol treatment) were limited to Grade 1 or 2, with no reported Grade 3 events. CONCLUSIONS This is the first clinical outcomes report from NRG Oncology RTOG 0539. Patients with intermediate-risk meningioma treated with RT had excellent 3-year PFS, with a low rate of local failure and a low risk of AEs. These results support the use of postoperative RT for newly diagnosed gross-totally resected WHO Grade II or recurrent WHO Grade I meningioma irrespective of resection extent. They also document minimal toxicity and high rates of tumor control with IMRT. Clinical trial registration no.: NCT00895622 (clinicaltrials.gov). PMID- 28984519 TI - Surgical management of incidentally discovered diffusely infiltrating low-grade glioma. AB - OBJECTIVE Occasionally, diffusely infiltrating low-grade gliomas (LGGs) are identified as incidental findings in patients who have no signs or symptoms that can be ascribed to the tumors. The diagnosis of incidental, asymptomatic LGGs has become more frequent due to the vast increase in access to medical imaging technology. While management of these lesions remains controversial, early surgery has been suggested to improve outcome. The authors set out to identify and review the characteristics and surgical outcomes of patients who underwent surgical intervention for incidental LGG. METHODS All cases of LGG surgically treated between 2004 and 2016 at the authors' institution were analyzed to identify those that were discovered incidentally. Patients with incidentally discovered LGGs were identified, and their cases were retrospectively reviewed. An "incidental" finding was defined as an abnormality on imaging that was obtained for a reason not attributable to the glioma, such as trauma, headache, screening, or research participation. Kaplan-Meier analysis was performed to determine actuarial rates of overall survival, progression-free survival, and malignant progression-free survival. RESULTS In 34 (6.8%) of 501 adult patients who underwent surgery for LGG, the tumors were discovered incidentally. Headache (26%, n = 9) and screening (21%, n = 7) were the most common indications for brain imaging in this group. Four of these 34 patients had initial biopsy after the tumor was identified on imaging. In 5 cases, the patients opted for immediate resection; the remaining cases were managed with a "watch-and-wait" approach, with intervention undertaken only after radiological or clinical evidence of disease progression. The mean duration of follow-up for all 34 cases was 5 years. Twelve patients (35.3%) had disease progression, with an average time to progression of 43.8 months (range 3-105 months). There were 5 cases (14.7%) of malignant progression and 4 deaths (11.8%). Oligodendroglioma was diagnosed in 16 cases (47%) and astrocytoma in 15 (44%). Twenty-five patients (74%) had IDH1 mutation and demonstrated prolonged survival. Only 2 patients had mild surgery related complications, and 16 patients (47%) developed epilepsy during the course of the disease. CONCLUSIONS In this retrospective analysis of cases of incidentally discovered LGGs, the tumors were surgically removed with minimal surgical risk. In patients with incidental LGGs there is improved overall survival relative to median survival for patients with symptomatic LGGS, which is likely attributable to the underlying favorable biology of the disease indicated by the presence of IDH1 mutation in 74% of the cases. PMID- 28984520 TI - Prediction of BRAF mutation status of craniopharyngioma using magnetic resonance imaging features. AB - OBJECTIVE Treatment with a BRAF mutation inhibitor might shrink otherwise refractory craniopharyngiomas and is a promising preoperative treatment to facilitate tumor resection. The aim of this study was to investigate the noninvasive diagnosis of BRAF-mutated craniopharyngiomas based on MRI characteristics. METHODS Fifty-two patients with pathologically diagnosed craniopharyngioma were included in this study. Polymerase chain reaction was performed on tumor tissue specimens to detect BRAF and CTNNB1 mutations. MRI manifestations-including tumor location, size, shape, and composition; signal intensity of cysts; enhancement pattern; pituitary stalk morphology; and encasement of the internal carotid artery-were analyzed by 2 neuroradiologists blinded to patient identity and clinical characteristics, including BRAF mutation status. Results were compared between the BRAF-mutated and wild-type (WT) groups. Characteristics that were significantly more prevalent (p < 0.05) in the BRAF mutated craniopharyngiomas were defined as diagnostic features. The minimum number of diagnostic features needed to make a diagnosis was determined by analyzing the receiver operating characteristic (ROC) curve. RESULTS Eight of the 52 patients had BRAF-mutated craniopharyngiomas, and the remaining 44 had BRAF WT tumors. The clinical characteristics did not differ significantly between the 2 groups. Interobserver agreement for MRI data analysis was relatively reliable, with values of Cohen kappa ranging from 0.65 to 0.97 (p < 0.001). A comparison of findings in the 2 patient groups showed that BRAF-mutated craniopharyngiomas tended to be suprasellar (p < 0.001), spherical (p = 0.005), predominantly solid (p = 0.003), and homogeneously enhancing (p < 0.001), and that patients with these tumors tended to have a thickened pituitary stalk (p = 0.014). When at least 3 of these 5 features were present, a tumor might be identified as BRAF mutated with a sensitivity of 1.00 and a specificity of 0.91. The area under the ROC curve for the sum of all 5 diagnostic criteria was 0.989 (p < 0.001). CONCLUSIONS The BRAF mutation status of craniopharyngiomas might be predicted using certain MRI features with relatively high sensitivity and specificity, thus offering potential guidance for the preoperative administration of BRAF mutation inhibitors. PMID- 28984521 TI - Idiopathic intracranial hypertension: 120-day clinical, radiological, and manometric outcomes after stent insertion into the dural venous sinus. AB - OBJECTIVE Idiopathic intracranial hypertension (IIH) is commonly associated with venous sinus stenosis. In recent years, transvenous dural venous sinus stent (DVSS) insertion has emerged as a potential therapy for resistant cases. However, there remains considerable uncertainty over the safety and efficacy of this procedure, in particular the incidence of intraprocedural and delayed complications and in the longevity of sinus patency, pressure gradient obliteration, and therapeutic clinical outcome. The aim of this study was to determine clinical, radiological, and manometric outcomes at 3-4 months after DVSS in this treated IIH cohort. METHODS Clinical, radiographic, and manometric data before and 3-4 months after DVSS were reviewed in this single-center case series. All venographic and manometric procedures were performed under local anesthesia with the patient supine. RESULTS Forty-one patients underwent DVSS venography/manometry within 120 days. Sinus pressure reduction of between 11 and 15 mm Hg was achieved 3-4 months after DVSS compared with pre-stent baseline, regardless of whether the procedure was primary or secondary (after shunt surgery). Radiographic obliteration of anatomical stenosis correlating with reduction in pressure gradients was observed. The complication rate after DVSS was 4.9% and stent survival was 87.8% at 120 days. At least 20% of patients developed restenosis following DVSS and only 63.3% demonstrated an improvement or resolution of papilledema. CONCLUSIONS Reduced venous sinus pressures were observed at 120 days after the procedure. DVSS showed lower complication rates than shunts, but the clinical outcome data were less convincing. To definitively compare the outcomes between DVSS and shunts in IIH, a randomized prospective study is needed. PMID- 28984522 TI - The V3 segment of the vertebral artery as a robust donor for intracranial-to intracranial interpositional bypasses: technique and application in 5 patients. AB - The V3 segment of the vertebral artery (VA) has been studied in various clinical scenarios, such as in tumors of the craniovertebral junction and dissecting aneurysms. However, its use as a donor artery in cerebral revascularization procedures has not been extensively studied. In this report, the authors summarize their clinical experience in cerebral revascularization procedures using the V3 segment as a donor. A brief anatomical description of the relevant techniques is also provided. PMID- 28984523 TI - Retreatment of vestibular schwannoma with Gamma Knife radiosurgery: clinical outcome, tumor control, and review of literature. AB - OBJECTIVE Gamma Knife radiosurgery (GKRS) has become an accepted treatment for vestibular schwannoma, with a high rate of tumor control and good clinical outcome. In a small number of cases, additional treatment is needed. This retrospective study examines the clinical outcome, reproducibility of volumetric response patterns, and tumor control rate after administering a second GKRS to treat vestibular schwannomas. METHODS A total of 38 patients were included: 28 patients underwent a radiosurgical procedure as the initial treatment (Group 1), and 10 patients underwent microsurgical resection with adjuvant radiosurgery on the tumor remnant as the initial treatment (Group 2). The indication for a second GKRS treatment was growth observed on follow-up imaging. The median margin dose was 11.0 Gy for the first procedure and 11.5 Gy for the second procedure. Tumor control after retreatment was assessed through volumetric analysis. Clinical outcome was assessed through medical chart review. RESULTS Median tumor volume at retreatment was 3.6 cm3, with a median treatment interval of 49 months. All patients showed tumor control in a median follow-up period of 75 months after the second radiosurgical procedure. Volumetric tumor response after the second procedure did not correspond to response after the first procedure. After retreatment, persisting House-Brackmann Grade II facial nerve dysfunction was observed in 3 patients (7.9%), facial spasms in 5 patients (13%), and trigeminal nerve hypesthesia in 3 patients (7.9%). Hearing preservation was not evaluated because of the small number of patients with serviceable hearing at the second procedure. CONCLUSIONS Repeat GKRS after a failed first treatment appears to be an effective strategy in terms of tumor control. The volumetric response after a repeat procedure could not be predicted by the volumetric response observed after first treatment. This justifies considering repeat GKRS even for tumors that do not show any volumetric response and show continuous growth after first treatment. An increased risk of mild facial and trigeminal nerve dysfunction was observed after the second treatment compared with the first treatment. PMID- 28984524 TI - Population Dynamics of Early Visual Cortex during Working Memory. AB - Although the content of working memory (WM) can be decoded from the spatial patterns of brain activity in early visual cortex, how populations encode WM representations remains unclear. Here, we address this limitation by using a model-based approach that reconstructs the feature encoded by population activity measured with fMRI. Using this approach, we could successfully reconstruct the locations of memory-guided saccade goals based on the pattern of activity in visual cortex during a memory delay. We could reconstruct the saccade goal even when we dissociated the visual stimulus from the saccade goal using a memory guided antisaccade procedure. By comparing the spatiotemporal population dynamics, we find that the representations in visual cortex are stable but can also evolve from a representation of a remembered visual stimulus to a prospective goal. Moreover, because the representation of the antisaccade goal cannot be the result of bottom-up visual stimulation, it must be evoked by top down signals presumably originating from frontal and/or parietal cortex. Indeed, we find that trial-by-trial fluctuations in delay period activity in frontal and parietal cortex correlate with the precision with which our model reconstructed the maintained saccade goal based on the pattern of activity in visual cortex. Therefore, the population dynamics in visual cortex encode WM representations, and these representations can be sculpted by top-down signals from frontal and parietal cortex. PMID- 28984525 TI - Brain Networks Related to Beta Oscillatory Activity during Episodic Memory Retrieval. AB - Evidence from fMRI has consistently located a widespread network of frontal, parietal, and temporal lobe regions during episodic retrieval. However, the temporal limitations of the fMRI methodology have made it difficult to assess the transient network dynamics by which these distributed regions coordinate activity. Recent evidence suggests that beta oscillations (17-20 Hz) are important for top-down control for memory suppression. However, the spatial limitations of the EEG methodology make it difficult to assess the relationship between these oscillatory signals and the distributed networks identified with fMRI. This study used simultaneous EEG/fMRI to identify networks related to beta oscillations during episodic retrieval. Participants studied adjectives and either imagined a scene (Place Task) or judged its pleasantness (Pleasant Task). During the recognition test, participants decided which task was performed with each word ("Old Place Task" or "Old Pleasant Task") or "New." EEG results revealed that posterior beta power was greater for new than old words. fMRI results revealed activity in a frontal, parietal network that was greater for old than new words, consistent with prior studies. Although overall beta power increases correlated with decreased activity within a predominantly parietal network, within the right dorsolateral and ventrolateral pFC, beta power correlated with BOLD activity more under conditions requiring more cognitive control and EEG/fMRI effects in the right frontal cortex correlated with BOLD activity in a frontoparietal network. Therefore, using simultaneous EEG and fMRI, the present results suggest that beta oscillations are related to postretrieval control operations in the right frontal cortex and act within a broader postretrieval control network. PMID- 28984526 TI - The Dorsal Attention Network Reflects Both Encoding Load and Top-down Control during Working Memory. AB - The dorsal attention network is consistently involved in verbal and visual working memory (WM) tasks and has been associated with task-related, top-down control of attention. At the same time, WM capacity has been shown to depend on the amount of information that can be encoded in the focus of attention independently of top-down strategic control. We examined the role of the dorsal attention network in encoding load and top-down memory control during WM by manipulating encoding load and memory control requirements during a short-term probe recognition task for sequences of auditory (digits, letters) or visual (lines, unfamiliar faces) stimuli. Encoding load was manipulated by presenting sequences with small or large sets of memoranda while maintaining the amount of sensory stimuli constant. Top-down control was manipulated by instructing participants to passively maintain all stimuli or to selectively maintain stimuli from a predefined category. By using ROI and searchlight multivariate analysis strategies, we observed that the dorsal attention network encoded information for both load and control conditions in verbal and visuospatial modalities. Decoding of load conditions was in addition observed in modality-specific sensory cortices. These results highlight the complexity of the role of the dorsal attention network in WM by showing that this network supports both quantitative and qualitative aspects of attention during WM encoding, and this is in a partially modality-specific manner. PMID- 28984527 TI - Corrigendum to "Analgesic Effect of Maternal Human Milk Odor on Premature Neonates: A Randomized Controlled Trial". AB - Baudesson de Chanville, A., Brevaut-Malaty, V., Garbi, A., Tosello, B., Baumstarck, K., Gire, C., & Le Cozannet, R. (2017). Analgesic effect of maternal human milk odor on premature neonates: A randomized controlled trial. Journal of Human Lactation, 33(2), 300-308. (Original DOI: 10.1177/0890334417693225) In this article that appeared in the May 2017 issue of Journal of Human Lactation, the following corrections are required due to an inadvertent omission by the research team authoring the paper. 1) Dr. Romain Le Cozannet has been added as an author. The corrected author list is as follows: Audrey Baudesson de Chanville, MD, Veronique Brevaut-Malaty, MD, Aurelie Garbi, MD, Barthelemy Tosello, MD, PhD, Karine Baumstarck, MD, PhD, Catherine Gire, MD, and Romain Le Cozannet, PhD 2) At the time this study was conducted, Dr. Le Cozannet was the scientific coordinator for Aroma Therapeutics in Marseille, France. The funding statement has been amended to include Aroma Therapeutics, which provided materials and technical and scientific support for this study. The corrected funding statement is also provided as follows: Funding The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by institutional grants from the French 2013 Appel d'Offre Recherche Clinique Assistance Publique, Hopitaux de Marseille. The sponsor was represented by Assistance Publique, Hopitaux de Marseille, France, whose role was to control the appropriateness of ethical and legal considerations. Aroma Therapeutics provided materials and technical and scientific support for this study. PMID- 28984529 TI - JHL News. PMID- 28984528 TI - Antidepressant Use in Late Gestation and Breastfeeding Rates at Discharge from Hospital. AB - BACKGROUND: Few studies have investigated breastfeeding outcomes among women exposed to antidepressants. Research aim: This study aimed to evaluate the association between antidepressant use in late gestation and maternal psychiatric illness on breastfeeding rates at discharge from hospital. METHODS: The authors conducted a retrospective cohort study of 32,662 women delivering live-born singletons between January 2001 and December 2008. Electronic hospital records were used to obtain data on antidepressant exposure during late gestation and whether mothers were breastfeeding at discharge from hospital following delivery. RESULTS: Five hundred seventy-five women received a dispensing for an antidepressant in late gestation (exposed), 1,552 did not receive a dispensing for an antidepressant but had a reported psychiatric illness (disease comparison), and 30,535 served as nonexposed controls. Exposed women were significantly less likely to be breastfeeding their infants at discharge from hospital compared with nonexposed women, adjusted odds ratio ( AOR) = 0.63, 95% confidence interval (CI) [0.50-0.80], but no statistically significant difference was observed when compared with women in the disease comparison group, AOR = 0.83, 95% CI [0.65-1.07]. In stratified analyses, compared with women in the disease comparison group, exposed women were significantly less likely to be breastfeeding their infants at discharge from hospital if their neonate was delivered at term, AOR = 0.73, 95% CI [0.55-0.98], but not preterm, AOR = 1.24, 95% CI [0.66-2.32]. CONCLUSION: While antidepressant use is associated with a reduction in breastfeeding rates, this association appears to be strongly influenced by factors such as underlying maternal psychiatric illness. Overall, these results highlight that these women may benefit from additional education and support to improve breastfeeding rates. PMID- 28984530 TI - Development and Evaluation of a Lactation Rotation for a Pediatric Residency Program. AB - BACKGROUND: The American Academy of Pediatrics recommends that pediatricians promote and help manage breastfeeding. However, research has shown that they are not adequately prepared. To address this gap, a 2-week mandatory lactation rotation program was developed for first-year pediatric residents. Research aim: The aim of the study was to provide a lactation education program and to measure the residents' knowledge and perceived confidence regarding breastfeeding. METHODS: This longitudinal self-report pretest/posttest study was conducted with a convenience sample of 45 first-year pediatric residents. Each resident spent a minimum of 50 hours with an International Board Certified Lactation Consultant. To measure breastfeeding knowledge and clinical confidence, the American Academy of Pediatrics' Breastfeeding Residency Curriculum pretest was used 4 times: first and last day of the rotation and at 6 and 12 months postrotation. RESULTS: Test and confidence scores were evaluated. Statistically significant differences in knowledge were found between test 1 when compared with tests 2, 3, and 4 ( p < .001). No significant differences were found between tests 2, 3, and 4 ( p > .05). The abilities to "adequately address parents' questions" and to "completely manage common problems" were significant, with confidence increasing in tests 2, 3, and 4 ( p < .001). CONCLUSION: As a result of an innovative, comprehensive educational lactation program, the pediatric residents' knowledge and perceived confidence related to breastfeeding significantly increased. PMID- 28984532 TI - Corrigendum to "Workplace Lactation Support in Milwaukee County 5 Years After the Affordable Care Act". AB - Lennon, T., Blackwell, D., & Willis, E. (2017). Workplace lactation support in Milwaukee county 5 years after the Affordable Care Act. Journal of Human Lactation, 33(1), 214-219. (Original DOI: 10.1177/0890334416679617) In this article that appeared in the February 2017 issue of Journal of Human Lactation, the following corrections are required due to an inadvertent omission by the research team authoring the paper. 1) Dalvery Blackwell has been added as an author. The corrected author list is as follows: Tyler Lennon, BS, Dalvery Blackwell, BA, IBCLC, and Earnestine Willis, MD, MPH 2) The authors sincerely appreciate the significant contribution that the African American Breastfeeding Network (AABN) had in this project that resulted in a publication and wish to acknowledge them for their outstanding efforts in the Milwaukee communities. The authors regret not providing an authorship to the AABN with the original manuscript submission. PMID- 28984533 TI - 12th Breastfeeding and Feminism International Conference: Breastfeeding as Social Justice: From Crucial Conversation to Inspired Action. PMID- 28984535 TI - Fluid biomarkers for disease activity in multiple sclerosis. PMID- 28984534 TI - Validation of a Theory of Planned Behavior-Based Questionnaire to Examine Factors Associated With Milk Expression. AB - BACKGROUND: A proper assessment of multidimensional needs for breastfeeding mothers in various settings is crucial to facilitate and support breastfeeding and its exclusivity. The theory of planned behavior (TPB) has been used frequently to measure factors associated with breastfeeding. Full utility of the TPB requires accurate measurement of theory constructs. Research aim: This study aimed to develop and confirm the psychometric properties of an instrument, Milk Expression on Campus, based on the TPB and to establish the reliability and validity of the instrument. METHODS: In spring 2015, 218 breastfeeding (current or in the recent past) employees and students at one university campus in northern New Jersey completed the online questionnaire containing demography and theory-based items. Internal consistency (alpha) and split-half reliability ( r) tests and factor analyses established and confirmed the reliability and construct validity of this instrument. RESULTS: Milk Expression on Campus showed strong and significant reliabilities as a full scale (alpha = .78, r = .74, p < .001) and theory construct subscales. Validity was confirmed as psychometric properties corresponded to the factors extracted from the scale. Four factors extracted from the direct construct subscales accounted for 79.49% of the total variability. Four distinct factors from the indirect construct subscales accounted for 73.68% of the total variability. CONCLUSION: Milk Expression on Campus can serve as a model TPB-based instrument to examine factors associated with women's milk expression behavior. The utility of this instrument extends to designing effective promotion programs to foster breastfeeding and milk expression behaviors in diverse settings. PMID- 28984536 TI - Airway injury in an in vitro human epithelium-fibroblast model of diacetyl vapor exposure: diacetyl-induced basal/suprabasal spongiosis. AB - Inhalation exposure to diacetyl (DA) is associated with obliterative bronchiolitis (OB) in workers and induces OB-like fibrotic airway lesions in rats. The pathogenesis of OB is poorly understood in part due to complex interactions between airway epithelial, mesenchymal and blood-derived inflammatory cells. DA-induced airway toxicity in the absence of recruited inflammatory/immune cells was characterized using an air-liquid interface (ALI) model consisting of human airway epithelium with (Epi/FT) and without (Epi) a mesenchymal component. ALI cultures were exposed to 25 mM DA-derived vapors (using vapor cups) for 1 h on day 0, 2 and 4. In some experiments, the tissues were exposed to 2,3-hexanedione (Hex) which is structurally-similar, but much less fibrogenic than DA. Lactate dehydrogenase activity and day 6 histopathologic changes associated with epithelial injury, including basal/suprabasal spongiosis, were increased following exposure of Epi/FT tissues to DA but not control or Hex vapors. IL-1a, IL-6, IL-8, sIL-1Ra, TGFa, MCP-3 and TNFa proteins were increased following DA exposure of Epi/FT tissues; only IL-1a, IL-8, sIL-1Ra and TGFa were increased following exposure of Epi tissues. MMP-1, MMP-3 and TIMP-1 proteins were increased following DA exposure of Epi/FT tissues; whereas MMP-2, MMP-7 and TIMP-2 were decreased, and production was largely dependent upon the presence of sub-epithelial stromal matrix/fibroblasts. Hex-induced protein changes were minimal. This in vitro study demonstrated that exposure of human airways to DA vapors induced epithelial injury (with the histopathologic feature of basal/suprabasal spongiosis) and increased release of pro-inflammatory and pro fibrotic cytokines/chemokines as well as MMPs/TIMPs in the absence of recruited inflammatory cells. PMID- 28984537 TI - Neurosurgical transection of the breast: an unexpected extracranial complication of ventriculoperitoneal shunt insertion. AB - Ventriculoperitoneal (VP) shunt placement is among the most common surgical procedures undertaken by neurosurgeons. Complications arising from the thoracic portion of the shunt are relatively rare in comparison with those of the intraventricular and peritoneal portions. Disruption of primary breast development following VP shunt placement has not previously been reported. The authors describe the case of a 15-year-old girl referred to the plastic surgery department with a significant right breast deformity and associated asymmetry following VP shunt placement performed during the neonatal period. The calcified shunt was excised and the breast deformity was corrected surgically through multiple scar tissue releases and restoration of the normal breast parenchymal anatomy via a minimally invasive approach, resulting in an excellent aesthetic outcome. This case highlights the potential for injury to occult breast tissue in pediatric patients undergoing VP shunt placement, which can impair subsequent cosmesis and quality of life. PMID- 28984538 TI - Lessons learned from administration of high-dose methylprednisolone sodium succinate for acute pediatric spinal cord injuries. AB - OBJECTIVE Methylprednisolone sodium succinate (MPSS) has been studied as a pharmacological adjunct that may be given to patients with acute spinal cord injury (ASCI) to improve neurological recovery. MPSS treatment became the standard of care in adults despite a lack of evidence supporting clinical benefit. More recently, new guidelines from neurological surgeon groups recommended no longer using MPSS for ASCI, due to questionable clinical benefit and known complications. However, little information exists in the pediatric population regarding MPSS use in the setting of ASCI. The aim of this paper was to describe steroid use and side effects in patients with ASCI at the authors' Level 1 pediatric trauma center in order to inform other hospitals that may still use this therapy. METHODS A retrospective chart review was conducted to determine adherence in ordering and delivery according to the guideline of the authors' institution and to determine types and frequency of complications. Inclusion criteria included age < 17 years, blunt trauma, physician concern for ASCI, and admission for >= 24 hours or treatment with high-dose intravenous MPSS. Exclusion criteria included penetrating trauma, no documentation of ASCI, and incomplete medical records. Charts were reviewed for a predetermined list of complications. RESULTS A total of 602 patient charts were reviewed; 354 patients were included in the study. MPSS was administered in 59 cases. In 34 (57.5%) the order was placed correctly. In 13 (38.2%) of these 34 cases, MPSS was administered according to the recommended timeline protocol. Overall, only 13 (22%) of 59 patients received the therapy according to protocol with regard to accurate ordering and administration. Among the patients with ASCI, 20 (55.6%) of the 36 who received steroids had complications, which was a significantly higher rate than in those who did not receive steroids (8 [24.2%] of 33, p = 0.008). Among the patients without ASCI, 10 (43.5%) of the 23 who received steroids also experienced significantly more complications than patients who did not receive steroids (50 [19.1%] of 262, p = 0.006). CONCLUSIONS High-dose MPSS for ASCI was not delivered to pediatric patients according to protocol with a high degree of reliability. Patients receiving steroids for pediatric ASCI were significantly more likely to experience complications than patients not receiving steroids. The findings presented, including complications of steroid use, support removal of high-dose MPSS as a treatment option for pediatric ASCI. PMID- 28984539 TI - The importance of extent of choroid plexus cauterization in addition to endoscopic third ventriculostomy for infantile hydrocephalus: a retrospective North American observational study using propensity score-adjusted analysis. AB - OBJECTIVE Combined endoscopic third ventriculostomy (ETC) and choroid plexus cauterization (CPC)-ETV/CPC- is being investigated to increase the rate of shunt independence in infants with hydrocephalus. The degree of CPC necessary to achieve improved rates of shunt independence is currently unknown. METHODS Using data from a single-center, retrospective, observational cohort study involving patients who underwent ETV/CPC for treatment of infantile hydrocephalus, comparative statistical analyses were performed to detect a difference in need for subsequent CSF diversion procedure in patients undergoing partial CPC (describes unilateral CPC or bilateral CPC that only extended from the foramen of Monro [FM] to the atrium on one side) or subtotal CPC (describes CPC extending from the FM to the posterior temporal horn bilaterally) using a rigid neuroendoscope. Propensity scores for extent of CPC were calculated using age and etiology. Propensity scores were used to perform 1) case-matching comparisons and 2) Cox multivariable regression, adjusting for propensity score in the unmatched cohort. Cox multivariable regression adjusting for age and etiology, but not propensity score was also performed as a third statistical technique. RESULTS Eighty-four patients who underwent ETV/CPC had sufficient data to be included in the analysis. Subtotal CPC was performed in 58 patients (69%) and partial CPC in 26 (31%). The ETV/CPC success rates at 6 and 12 months, respectively, were 49% and 41% for patients undergoing subtotal CPC and 35% and 31% for those undergoing partial CPC. Cox multivariate regression in a 48-patient cohort case-matched by propensity score demonstrated no added effect of increased extent of CPC on ETV/CPC survival (HR 0.868, 95% CI 0.422-1.789, p = 0.702). Cox multivariate regression including all patients, with adjustment for propensity score, demonstrated no effect of extent of CPC on ETV/CPC survival (HR 0.845, 95% CI 0.462-1.548, p = 0.586). Cox multivariate regression including all patients, with adjustment for age and etiology, but not propensity score, demonstrated no effect of extent of CPC on ETV/CPC survival (HR 0.908, 95% CI 0.495-1.664, p = 0.755). CONCLUSIONS Using multiple comparative statistical analyses, no difference in need for subsequent CSF diversion procedure was detected between patients in this cohort who underwent partial versus subtotal CPC. Further investigation regarding whether there is truly no difference between partial versus subtotal extent of CPC in larger patient populations and whether further gain in CPC success can be achieved with complete CPC is warranted. PMID- 28984540 TI - Evolution of the postoperative sagittal spinal profile in early-onset scoliosis: is there a difference between rib-based and spine-based growth-friendly instrumentation? AB - OBJECTIVE Although the vertical expandable prosthetic titanium rib (VEPTR) and growing rod instrumentation (GRI) encourage spinal growth via regular lengthening, they can create different results because of their different fixation patterns and mechanisms in correcting scoliosis. Previous studies have focused comparisons on coronal plane deformity with minimal attention to the sagittal profile. In this retrospective study, the authors aimed to compare the evolution of the sagittal spinal profile in early-onset scoliosis (EOS) treated with VEPTR versus GRI. METHODS The data for 11 patients with VEPTR and 22 with GRI were reviewed. All patients had more than 2 years' follow-up with more than 2 lengthening procedures. Radiographic measurements were performed before and after the index surgery and at the latest follow-up. The complications in both groups were recorded. RESULTS Patients in both groups had similar diagnoses, age at the index surgery, and number of lengthening procedures. The changes in the major coronal Cobb angle and T1-S1 spinal height were not significantly different between the 2 groups. Compared with the GRI group, the VEPTR group had less correction in thoracic kyphosis (23% +/- 12% vs 44% +/- 16%, p < 0.001) after the index surgery and experienced a greater correction loss in thoracic kyphosis (46% +/- 18% vs 11% +/- 8%, p < 0.001) at the latest follow-up. Although the increase in the proximal junctional angle was not significantly different (VEPTR: 7 degrees +/- 4 degrees vs GRI: 8 degrees +/- 5 degrees , p = 0.569), the incidence of proximal junctional kyphosis was relatively lower in the VEPTR group (VEPTR: 18.2% vs GRI: 22.7%). No significant changes in the spinopelvic parameters were observed, while the sagittal vertical axis showed a tendency toward a neutral position in both groups. The overall complication rate was higher in the VEPTR group than in the GRI group (72.7% vs 54.5%). CONCLUSIONS The VEPTR had coronal correction and spinal growth results similar to those with GRI. In the sagittal plane, however, the VEPTR was not comparable to the GRI in controlling thoracic kyphosis. Thus, for hyperkyphotic EOS patients, GRI is recommended over VEPTR. PMID- 28984542 TI - Tenacibaculum aestuariivivum sp. nov., isolated from a tidal flat. AB - A Gram-stain-negative, aerobic, non-motile, non-spore-forming bacterial strain, designated JDTF-79T, was isolated from a tidal flat in Jindo, an island of South Korea, and subjected to a taxonomic study using a polyphasic approach. Strain JDTF-79T grew optimally at 25 degrees C and in the presence of 2.0 % (w/v) NaCl. Phylogenetic trees based on 16S rRNA gene sequences showed that strain JDTF-79T fell within the clade comprising the type strains of species of the genus Tenacibaculum, clustering with the type strains of Tenacibaculum dicentrarchi, Tenacibaculum ovolyticum, 'Tenacibaculum haliotis' and Tenacibaculum soleae. The novel strain exhibited highest 16S rRNA gene sequence similarity (98.3 %) to the type strain of T. dicentrarchi and sequence similarities of 93.5-96.9 % to the type strains of the other species of the genus Tenacibaculum. Strain JDTF-79T contained MK-6 as the predominant menaquinone and anteiso-C15 : 0, iso-C15 : 0 3 OH and iso-C15 : 0 as the major fatty acids. The major polar lipids of strain JDTF-79T were phosphatidylethanolamine, one unidentified lipid and one unidentified aminophospholipid. The DNA G+C content of strain JDTF-79T was 30.3 mol%. Strain JDTF-79T had a mean DNA-DNA relatedness value of 19 % with the type strain of T. dicentrarchi. The differential phenotypic properties, together with the phylogenetic and genetic data, revealed that strain JDTF-79T is separated from other recognized species of the genus Tenacibaculum. On the basis of the data presented, strain JDTF-79T is considered to represent a novel species of the genus Tenacibaculum, for which the name Tenacibaculum aestuariivivum sp. nov. is proposed. The type strain is JDTF-79T (=KCTC 52980T=NBRC 112903T). PMID- 28984541 TI - Isolated optic nerve gliomas: a multicenter historical cohort study. AB - OBJECTIVE Isolated optic nerve gliomas (IONGs) constitute a rare subgroup of optic pathway gliomas (OPGs). Due to the rarity of this condition and the difficulty in differentiating IONGs from other types of OPGs in most clinical series, little is known about these tumors. Currently, due to lack of evidence, they are managed the same as any other OPG. METHODS The authors conducted a multicenter retrospective cohort study aimed at determining the natural history of IONGs. Included were patients with clear-cut glioma of the optic nerve without posterior (chiasmatic/hypothalamic) involvement. At least 1 year of follow-up, 2 MRI studies, and 2 neuro-ophthalmological examinations were required for inclusion. RESULTS Thirty-six patients with 39 tumors were included in this study. Age at diagnosis ranged between 6 months and 16 years (average 6 years). The mean follow-up time was 5.6 years. Twenty-five patients had neurofibromatosis Type 1. During the follow-up period, 59% of the tumors progressed, 23% remained stable, and 18% (all with neurofibromatosis Type 1) displayed some degree of spontaneous regression. Fifty-one percent of the patients presented with visual decline, of whom 90% experienced further deterioration. Nine patients were treated with chemotherapy, 5 of whom improved visually. Ten patients underwent operation, and no local or distal recurrence was noted. CONCLUSIONS Isolated optic nerve gliomas are highly dynamic tumors. Radiological progression and visual deterioration occur in greater percentages than in the general population of patients with OPGs. Response to chemotherapy may be better in this group, and its use should be considered early in the course of the disease. PMID- 28984543 TI - Phaeobacter piscinae sp. nov., a species of the Roseobacter group and potential aquaculture probiont. AB - Four heterotrophic, antimicrobial, motile, marine bacterial strains, 27-4T, 8-1, M6-4.2 and S26, were isolated from aquaculture units in Spain, Denmark and Greece. All four strains produced the antibiotic compound tropodithietic acid, which is a key molecule in their antagonism against fish pathogenic bacteria. Cells of the strains were Gram-reaction-negative, rod-shaped and formed star shaped aggregates in liquid culture and brown-coloured colonies on marine agar. The predominant cellular fatty acids were C18 : 1omega7c, C16 : 0, C11 methyl C18 : 1omega7c and C16 : 0 2-OH, and the polar lipids comprised phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, an aminolipid, a phospholipid and an unidentified lipid. The strains grew optimally at 31-33 degrees C. Growth was observed at a salt concentration between 0.5 and 5-6 % NaCl with an optimum at 2-3 %. The pH range for growth of the strains was from pH 6 to 8-8.5 with an optimum at pH 7. Based on 16S rRNA gene sequence analysis, the strains are affiliated with the genus Phaeobacter. The genome sequences of the strains have a DNA G+C content of 60.1 % and share an average nucleotide identity (ANI) of more than 95 %. The four strains are distinct from the type strains of the closely related species Phaeobactergallaeciensis and Phaeobacterinhibens based on an ANI of 90.5-91.7 and 89.6-90.4 %, respectively, and an in silico DNA-DNA hybridization relatedness of 43.9-46.9 and 39.8-41.9 %, respectively. On the basis of phylogenetic analyses as well as phenotypic and chemotaxonomic properties, the isolates are considered to represent a novel species, for which the name Phaeobacter piscinae sp. nov. is proposed. The type strain is 27-4T (=DSM 103509T=LMG 29708T). PMID- 28984544 TI - Anoxynatronum buryatiense sp. nov., an anaerobic alkaliphilic bacterium from a low mineralization soda lake in Buryatia, Russia. AB - An anaerobic alkaliphilic, proteolytic bacterium, strain Su22T, was isolated from the bottom sediment of the alkaline low mineralization lake Sulphatnoe (Selenginsky district, Buryatia, Russia). A comparative analysis of the 16S rRNA gene sequence revealed that this bacterium was closely related to Anoxynatronum sibiricum Z-7981T with a similarity of 98.1 %. Strain Su22T differed from A. sibiricum Z-7981T in its inability to use carbohydrates, peptone and amino acids as carbon sources. Strain Su22T grew over a temperature range of 20-40 degrees C with an optimum at 30 degrees C and within the pH range 7.4-11.0 with an optimum at pH 9.6. Sodium cations stimulated the growth of the strain considerably with an optimal concentration at 0.76-1.09 M. The whole-cell fatty acid profile included C16 : 1omega7c, C16 : 0 and C16 : 0 ALDE. The G+C content was 46.1 mol%. Based on the DNA-DNA hybridization level (53.2 %) and phenotypical differences between strains Su22T and Z-7981T, the new isolate is thus considered to represent a novel species, for which the name Anoxynatronumburyatiense sp. nov. is proposed. The type strain is Su22T (=VKM B-2510T=CECT 8731T). PMID- 28984545 TI - Planktotalealamellibrachiae sp. nov., isolated from a marine organism in Kagoshima Bay, Japan. AB - A novel marine bacterial strain, designated JAM 119T, was isolated from a tubeworm trophosome in Kagoshima Bay, Japan. Cells were Gram-negative, rod shaped, non-spore-forming aerobic chemoorganotrophs and motile by means of a single polar flagellum. The isolate grew optimally at 25-27 degrees C and in the presence of 3 % NaCl. The major respiratory quinone was Q-10. The predominant fatty acid was C18 : 1omega7c. Phosphatidylcholine, phosphatidylglycerol and an unidentified aminolipid were the major polar lipids. On the basis of 16S rRNA gene sequence analysis, the isolated strain was closely affiliated with members of the genus Planktotalea in the class Alphaproteobacteria, and the 16S rRNA gene sequence similarity of the new isolates with the closest related species, Planktotalea frisia SH6-1T, was 97.3 %. The DNA G+C content of the novel strain was 57.0 mol%. Based on differences in taxonomic characteristics, the isolated strain represents a novel species of the genus Planktotalea, for which the name Planktotalealamellibrachiae sp. nov. (type strain JAM 119T; JCM 31859T=DSMZ 104669T) is proposed. PMID- 28984546 TI - Mycobacterium grossiae sp. nov., a rapidly growing, scotochromogenic species isolated from human clinical respiratory and blood culture specimens. AB - A previously undescribed, rapidly growing, scotochromogenic species of the genus Mycobacterium (represented by strains PB739T and GK) was isolated from two clinical sources - the sputum of a 76-year-old patient with severe chronic obstructive pulmonary disease, history of tuberculosis exposure and Mycobacterium avium complex isolated years prior; and the blood of a 15-year-old male with B cell acute lymphoblastic leukaemia status post bone marrow transplant. The isolates grew as dark orange colonies at 25-37 degrees C after 5 days, sharing features in common with other closely related species. Analysis of the complete 16S rRNA gene sequence (1492 bp) of strain PB739T demonstrated that the isolate shared 98.8 % relatedness with Mycobacterium wolinskyi. Partial 429 bp hsp65 and 744 bp rpoB region V sequence analyses revealed that the sequences of the novel isolate shared 94.8 and 92.1 % similarity with those of Mycobacterium neoaurum and Mycobacterium aurum, respectively. Biochemical profiling, antimicrobial susceptibility testing, HPLC/gas-liquid chromatography analyses and multilocus sequence typing support the taxonomic status of these isolates (PB739T and GK) as representatives of a novel species. Both isolates were susceptible to the Clinical and Laboratory Standards Institute recommended antimicrobials for susceptibility testing of rapidly growing mycobacteria including amikacin, ciprofloxacin, moxifloxacin, doxycycline/minocycline, imipenem, linezolid, clarithromycin and trimethropin/sulfamethoxazole. Both isolates PB739T and GK showed intermediate susceptibility to cefoxitin. We propose the name Mycobacterium grossiae sp. nov. for this novel species and have deposited the type strain in the DSMZ and CIP culture collections. The type strain is PB739T (=DSM 104744T=CIP 111318T). PMID- 28984547 TI - Cohnella algarum sp. nov., isolated from a freshwater green alga Paulinella chromatophora. AB - A Gram-stain-positive, facultatively aerobic and endospore-forming bacterium, designated strain Pch-40T, was isolated from a freshwater green alga, Paulinella chromatophora. Cells were motile rods with a monotrichous polar flagellum showing catalase- and oxidase-positive reactions. Strain Pch-40T grew at 20-50 degrees C (optimum, 37-40 degrees C), at pH 5.0-11.0 (optimum, pH 7.0) and in the presence of 0-4.0 % (w/v) NaCl (optimum, 0 %). Menaquinone-7 was detected as the sole isoprenoid quinone. The genomic DNA G+C content of strain Pch-40T was 55.6 mol%. The major cellular fatty acids of strain Pch-40T were C16 : 0, iso-C16 : 0, anteiso-C15 : 0 and anteiso-C17 : 0. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain Pch 40T clearly belonged to the genus Cohnella of the family Paenibacillaceae. Strain Pch-40T was most closely related to Cohnella rhizosphaerae CSE-5610T with a 96.1 % 16S rRNA gene sequence similarity. The phenotypic and chemotaxonomic features and the phylogenetic inference clearly suggested that strain Pch-40T represents a novel species of the genus Cohnella, for which the name Cohnellaalgarum sp. nov. is proposed. The type strain is strain Pch-40T (=KACC 19279T=JCM 32033T). PMID- 28984548 TI - Arthrobacter silviterrae sp. nov., isolated from forest soil. AB - A novel actinomycete strain, designated KIS14-16T, was isolated from forest soil in Ongjin county, South Korea and characterized using polyphasic taxonomy. The cells are aerobic, Gram-stain-positive, non-flagellated and short rods. The strain grew in a temperature range of 4-33 degrees C (optimum, 28-30 degrees C) and pH range of 5.0-10.0 (optimum, 7.0) and in the presence of 0-5 % (w/v) NaCl (optimum, 0 %). Comparison of 16S rRNA gene sequences showed that strain KIS14 16T is a member of the genus Arthrobacter exhibiting high sequence similarity with A. livingstonensis LI2T (97.7 %), A. cryoconiti Cr6-08T (97.6 %), A. psychrochitiniphilus GP3T (97.4 %), A. stackebrandtii CCM 2783T (97.1 %) and A. globiformis DSM 20124T (96.3 %). DNA-DNA relatedness and phenotypic data distinguished strain KIS14-16T from phylogenetically related type strains. The peptidoglycan type of strain KIS14-16T was A3alpha, with an interpeptide bridge comprising l-Lys, l-Thr, Gly and l-Ala4. Strain KIS14-16T contained a large amount of MK-9(H2) and relatively small amounts of MK-10(H2) and MK-8(H2). The main polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol and dimannosylglyceride. The major fatty acids (>10 %) were anteiso-C15 : 0 and anteiso-C17 : 0. The genomic DNA G+C content was 63.9 mol%. On the basis of these phenotypic, chemotaxonomic and phylogenetic data, strain KIS14-16T should be designated as a representative novel species of the genus Arthrobacter, for which the name Arthrobacter silviterrae sp. nov. is proposed. The type strain is KIS14-16T (=KACC 17303T=DSM 27180T=NBRC 109660T). PMID- 28984549 TI - Seonamhaeicola marinus sp. nov., isolated from marine algae. AB - A Gram-stain-negative, facultatively anaerobic, rod-shaped, non-flagellated and non-gliding bacterium, designated strain B011T, was isolated from marine algae Gracilaria blodgettii collected from the coast of Lingshui county, Hainan, China. Phylogenetic analysis of 16S rRNA gene sequences revealed that strain B011T, Seonamhaeicola algicola (96.8 % 16S rRNA gene sequence similarity) and Seonamhaeicola aphaedonensis (95.0 %) belonged to the same clade. Optimal growth occurred in the presence of 3.0 % (w/v) NaCl, at pH 6.5-7.5 and at 28 degrees C. Menaquinone-6 (MK-6) was the predominant respiratory quinone. The major fatty acids (>10 %) were iso-C15 : 1 G (23.4 %) and iso-C15 : 0 (22.8 %). The major polar lipids were phosphatidylethanolamine, one aminolipid and three unknown lipids. The DNA G+C content of strain B011T was 33.9 mol%. On the basis of polyphasic analysis, strain B011T is considered to represent a novel species in the genus Seonamhaeicola, for which the name Seonamhaeicolamarinus sp. nov. is proposed. The type strain is B011T (=MCCC 1H00146T=NBRC 112333T). PMID- 28984550 TI - Lysobacter olei sp. nov., isolated from oil-contaminated soil. AB - Strain D-14T, a brown-coloured, Gram-stain-negative, non-motile and rod-shaped bacterium, was isolated from oil-contaminated soil. It was able to grow at 20-40 degrees C, at pH 6.0-10.0 and at 0-1 % (w/v) NaCl concentration. Based on the 16S rRNA gene sequence analysis, strain D-14T belonged to the genus Lysobacter and was closely related to Lysobacter caeni BUT-8T (99.0 % sequence similarity), Lysobacter ruishenii CTN-1T (98.5 %), Lysobacter daejeonensis GH1-9T (98.2 %) and Lysobacter panacisoli CJ29T (97.2 %). The only respiratory quinone was ubiquinone 8. The polar lipid profile revealed the presence of phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and phosphatidyl-N-methyl ethanolamine. The predominant fatty acids of strain D-14T were iso-C15 : 0, iso C16 : 0, summed feature 9 (iso-C17 : 1 omega9c and/or C16 : 0 10-methyl), summed feature 3 (C16 : 1 omega7c and/or C16 : 1 omega6c), iso-C14 : 0, C11 : 0iso 3-OH, C15 : 1iso F and C16 : 0. The genomic DNA G+C content of this novel strain was 68.7 mol%. The DNA-DNA relatedness values between strain D-14T and L. caeni BUT 8T, L. ruishenii CTN-1T, L. daejeonensis GH1-9T and L. panacisoli CJ29T were 56.0, 46.3, 48.7 and 41.7 %, respectively, which fall below the threshold value of 70 % for the strain to be considered as novel. The morphological, physiological, chemotaxonomic and phylogenetic analyses clearly distinguished this strain from its closest phylogenetic neighbours. Thus, strain D-14T represents a novel species of the genus Lysobacter, for which the name Lysobacterolei sp. nov. is proposed. The type strain is D-14T (=KEMB 9005 572T=KACC 19173T=JCM 31917T). PMID- 28984551 TI - Chitinimonas lacunae sp. nov., isolated from artificial pond in Korea. AB - A gram-negative, rod shaped bacterium designated as strain H2T was isolated from an artificial pond in Korea. The strain H2T was able to grow aerobically and anaerobically with optimal growth occurring at 30 degrees C and pH 7.0 under aerobic conditions. Phylogenetic analysis based on 16S rRNA gene sequences showed that the strain H2T belonged to the genus Chitinimonas of the family Burkholderiaceae. Phylogenetic similarity calculated from 16S rRNA gene sequences of strain H2T and valid species belongs to the genus Chitinimonas ranged from 93.2 % (for Chitinimonas taiwanensis cfT) to 94.4 % (for Chitinimonas prasina LY03T), and strain H2T formed a tight monophyletic group with them. Predominant fatty acids were C16 : 0 and summed feature 3, which consisted of C16 : 1omega6c and/or C16 : 1omega7c. The major respiratory quinone of the strain H2T was ubiquinone-8, and DNA G+C content was 60.2 %. The polar lipids consisted of phosphatidylethanolamine, phosphatidylglycerol, unidentified aminolipid, and unidentified phospholipid. The biochemical characteristics that distinguished strain H2T from other Chitinimonas species included positive cystine arylamidase activity and lacked alpha-chymotrypsin and beta-glucosidase (aesculin hydrolysis) activity. In addition, reciprocal DNA-DNA relatedness between H2T and three Chitinimonas strains ranged from 32.0 to 43.7 %. On the basis of its phylogenetic, chemotaxonomic, and genotypic characteristics, strain H2T represents a novel species of the genus Chitinimonas. Chitinimonas lacunae sp. nov. is proposed with the type strain H2T (=KCTC 52574T=LMG 29894T). PMID- 28984552 TI - Paraglaciecola aestuariivivens sp. nov., isolated from a tidal flat. AB - A Gram-stain-negative, singly flagellated, aerobic and coccoid, ovoid or rod shaped bacterium, designated strain JDTF-33T, was isolated from a tidal flat in Jindo, an island of South Korea. Strain JDTF-33T grew optimally at 30 degrees C, at pH 7.0-8.0 and in the presence of 2.0-3.0 % (w/v) NaCl. A neighbour-joining phylogenetic tree, based on 16S rRNA gene sequences, demonstrated that strain JDTF-33T belonged to the genus Paraglaciecola, joining the type strain of the species Paraglaciecola aquimarinawith 97.9 % sequence similarity. Strain JDTF-33T exhibited 16S rRNA gene sequence similarities of 97.1 and 97.0 % to the type strains of Paraglaciecola arctica and Paraglaciecola psychrophila, respectively, and of 96.1-96.6 % to the type strains of the other species of the genus Paraglaciecola. Strain JDTF-33T showed DNA-DNA relatedness values of 11-24 % to the type strains of the species P. aquimarina, P. arctica and Paraglaciecola psychrophila. Strain JDTF-33T contained Q-8 as the predominant ubiquinone and summed feature 3 (C16 : omega7c and/or C16 : 1omega6c) and C16 : 0 as the major fatty acids. The major polar lipids detected in strain JDTF-33T were phosphatidylcholine, phosphatidylglycerol and phosphatidylethanolamine. The DNA G+C content of strain JDTF-33T was 41.7 mol%. Differential phenotypic properties, together with phylogenetic and genetic data, demonstrate that strain JDTF-33T is separate from species of the genus Paraglaciecolawith validly published names. On the basis of the data presented, strain JDTF-33T represents a novel species of the genus Paraglaciecola, for which the name Paraglaciecola aestuariivivens sp. nov. is proposed. The type strain is JDTF-33T (=KCTC 52838T=NBRC 112782T). PMID- 28984553 TI - Salsuginimonas clara gen. nov., sp. nov., a member of the family Pseudoalteromonadaceae isolated from a brackish river. AB - A bacterial strain designated LSN-49T was isolated from a brackish river in Taiwan and characterized using a polyphasic taxonomy approach. Cells of strain LSN-49T were Gram-staining-negative, aerobic, poly-beta-hydroxybutyrate accumulating, motile by means of a monopolar flagellum, non-spore forming, straight rods and formed shiny and translucent colonies. Growth occurred at 20-40 degrees C (optimum, 25-30 degrees C), at pH 6-10 (optimum, pH 7-8) and with 0-3 % (w/v) NaCl [optimum, 0-1 % (w/v)]. The predominant fatty acids were summed feature 3 (comprising C16 : 1omega7c and/or C16 : 1omega6c), C17 : 1omega8c and C16 : 0. The polar lipid profile consisted of a mixture of phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phosphatidylcholine, (PC), two uncharacterized aminophospholipids (APL1 and APL2), one uncharacterized glycolipid (GL1), four uncharacterized phospholipids (PL1-PL4) and four uncharacterized lipids (L1-L4). The major polyamine was putrescine. The major isoprenoid quinone was Q-8 and the DNA G+C content was 51.0 mol%. The results of phylogenetic analyses based on 16S rRNA gene sequences indicated that LSN-49T formed a distinct lineage with respect to closely related genera in the family Pseudoalteromonadaceae. LSN-49T was most closely related to Pseudoalteromonas, Algicola and Psychrosphaera and showed 89.3-92.1 % sequence similarity with members of the family Pseudoalteromonadaceae with validly published names. On the basis of the genotypic and phenotypic data, LSN-49T represents a novel genus and species of the family Pseudoalteromonadaceae, for which the name Salsuginimonas clara gen. nov., sp. nov. is proposed. The type strain is LSN-49T (=BCRC 81005T=LMG 29726T=KCTC 52439T). PMID- 28984554 TI - Characterization of the first rice paddy cluster I isolate, Methyloterricola oryzae gen. nov., sp. nov. and amended description of Methylomagnum ishizawai. AB - Three gammaproteobacterial methanotrophic strains (73aT, 175 and 114) were isolated from stems of rice plants. All strains are Gram-negative, motile and grow on methane or methanol as sole carbon sources. They oxidize methane using the particulate methane monooxygenase. Strains 114 and 175 possess additionally a soluble methane monooxygenase. All strains contain significant amounts of the cellular fatty acids C16 : 0, C16 : 1omega6c and C16 : 1omega7c, typical for type Ib methanotrophs. Characteristic for strains 114 and 175 are high amounts of C14 : 0 and C16 : 1omega6c , while strain 73aT contains high quantities of C16 : 1omega5c. 16S rRNA gene sequence analyses showed that strains 114 and 175 are most closely related to Methylomagnum ishizawai (>=99.6 % sequence identity). Strain 73aT is representing a new genus within the family Methylococcaceae, most closely related to Methylococcus capsulatus (94.3 % sequence identity). Phylogenetic analysis of the PmoA sequence indicates that strain 73aT represents rice paddy cluster I (RPCI), which has almost exclusively been detected in rice ecosystems. The G+C content of strain 73aT is 61.0 mol%, while strains 114 and 175 have a G+C content of 63.3 mol%. Strain 73aT (=LMG 29185T, =VKM B-2986T) represents the type strain of a novel species and genus, for which the name Methyloterricola oryzae gen. nov., sp. nov. is proposed and a description is provided. Strains 175 (=LMG 28717, VKM B-2989) and 114 are members of the species Methylomagnum ishizawai. This genus was so far only represented by one isolate, so an amended description of the species is given. PMID- 28984555 TI - Paracoccus litorisediminis sp. nov., isolated from a tidal flat. AB - A Gram-stain-negative, non-spore-forming, non-motile and coccoid, ovoid or short rod-shaped bacterial strain, designated GHD-05T, was isolated from a tidal flat on the Yellow Sea in South Korea. Strain GHD-05T grew optimally at 30 degrees C, at pH 7.0-8.0 and in the presence of 2.0 % (w/v) NaCl. The phylogenetic trees based on 16S rRNA gene sequences showed that strain GHD-05T belonged to the genus Paracoccus, clustering with the type strain of Paracoccusaestuariivivens. Strain GHD-05T exhibited 16S rRNA gene sequence similarity values of 97.0-99.1 % to the type strains of Paracoccusaestuariivivens, Paracoccuslimosus, Paracoccuslaeviglucosivorans and Paracoccusmarinus, and of 94.2-96.9 % to the type strains of the other Paracoccus species. Strain GHD-05T contained Q-10 as the predominant ubiquinone and C18 : 1omega7c as the major fatty acid. The major polar lipids detected in strain GHD-05T were phosphatidylcholine, phosphatidylglycerol, diphosphatidylglycerol, one unidentified aminolipid and one unidentified glycolipid. The DNA G+C content of strain GHD-05T was 64.1 mol% and its DNA-DNA relatedness values with the type strains of P. aestuariivivens, Paracoccuslimosus, P. laeviglucosivorans and P. marinus were 13-32 %. Differential phenotypic properties, together with its phylogenetic and genetic distinctiveness, revealed that strain GHD-05T is separated from recognized Paracoccus species. On the basis of the data presented here, strain GHD-05T is considered to represent a novel species of the genus Paracoccus, for which the name Paracoccuslitorisediminis sp. nov. is proposed. The type strain is GHD-05T (=KCTC 52978T=NBRC 112902T). PMID- 28984556 TI - Pseudomonas tarimensis sp. nov., an endophytic bacteria isolated from Populus euphratica. AB - An endophytic bacterium, MA-69T, was isolated from the storage liquid in the stems of Populuseuphratica trees at the ancient Ugan River in Xinjiang, PR China. Strain MA-69T was found to be short rod-shaped, Gram-stain-negative, non-spore forming, aerobic and motile by means of a monopolar flagellum. According to phylogenetic analysis based on 16S rRNA gene sequences, strain MA-69T was assigned to the genus Pseudomonas with highest 16S rRNA gene sequence similarity of 97.5 % to Pseudomonas azotifigens JCM 12708T, followed by Pseudomonas matsuisoli JCM 30078T (97.5 %), Pseudomonas balearica DSM 6083T (97.1 %), Azotobacter salinestris ATCC 49674T (96.1 %) and Pseudomonas indica DSM 14015T (95.9 %). Analysis of strain MA-69T based on the three housekeeping genes, rpoB, rpoD and gyrB, further confirmed the isolate to be distinctly delineated from species of the genus Pseudomonas. The DNA G+C content of strain MA-69T was 64.1 mol%. DNA-DNA hybridization with Pseudomonas azotifigens JCM 12708T, Pseudomonas matsuisoli JCM 30078T and Pseudomonas balearica DSM 6083T revealed 62.9, 60.1 and 49.0 % relatedness, respectively. The major fatty acids in strain MA-69T were summed feature 3 (25.7 %), summed feature 8 (24.0 %), C19 : 0cyclo omega8c (19.9 %), C16 : 0 (14.6 %) and C12 : 0 (6.3 %). The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. Q-9 was the major quinone in strain MA-69T. Based on phenotypic, chemotaxonomic and phylogenetic properties, strain MA-69T represents a novel species of the genus Pseudomonas, for which the name Pseudomonas tarimensis sp. nov. is proposed. The type strain is MA-69T (=CCTCC AB 2013065T=KCTC 42447T). PMID- 28984557 TI - Puia dinghuensis gen. nov., sp. nov., isolated from monsoon evergreen broad leaved forest soil. AB - A Gram-stain-negative, rod-shaped, aerobic, non-motile bacterial strain, 4GSH07T, was originally isolated from the monsoon evergreen broad-leaved forest soil of Dinghushan Biosphere Reserve, Guangdong Province, PR China (112 degrees 31' E 23 degrees 10' N). It grew optimally at 28-33 degrees C and pH 4.0. The 16S rRNA gene sequence analysis showed that strain 4GSH07T had the highest sequence similarity of 94.0 % to Parasegetibacter terrae JCM 19942T, and formed an independent lineage separable from other described genera of the family Chitinophagaceae. The main fatty acids (>5 %) were iso-C15 : 0, iso-C17 : 0 3-OH, C16 : 0 3-OH, summed feature 3 (C16 : 1omega6c and/or C16 : 1omega7c) and C15 : 0 2-OH. The organism contained MK-7 as the predominant respiratory quinone, and the total DNA G+C content was 50.3 mol%. The phenotypic, chemotaxonomic and phylogenetic data showed consistently that strain 4GSH07T represents a novel species of a novel genus of the family Chitinophagaceae, for which the name Puia dinghuensis gen. nov., sp. nov., is proposed, with 4GSH07T (=CGMCC 1.15448T=LMG 29214T) as the type strain. PMID- 28984558 TI - Porphyrobacter algicida sp. nov., an algalytic bacterium isolated from seawater. AB - A novel Gram-stain-negative, yellow-pigmented, catalase- and oxidase-positive, non-endospore-forming, flagellated bacterium, designated strain Yeonmyeong 2-22T, was isolated from surface seawater of Geoje Island, Republic of Korea. Strain Yeonmyeong 2-22T showed algalytic activity against the seven strains tested: Cochlodinium polykrikoides, Chattonella marina, Heterosigma akashiwo, Scrippsiella trochoidea, Heterocapsa triquetra, Prorocentrum minimum and Skeletonema costatum. A taxonomic study was carried out based on a polyphasic approach to characterize the exact taxonomic position of strain Yeonmyeong 2-22T. The bacterium was able to grow at 10-40 degrees C, at salinities from 0 to 9 %, at pH from 4.0 to 9.0 and was not able to degrade gelatin or casein. Phylogenetic analysis of 16S rRNA gene sequences revealed that strain Yeonmyeong 2-22T was considered to represent a novel species of the genus Porphyrobacter, which belongs to the family Erythrobacteraceae, and was related most closely to Porphyrobacter dokdonensis DSW-74T with 97.23 % 16S rRNA gene sequence similarity. The dominant cellular fatty acids of strain Yeonmyeong 2-22T were C18 : 1omega7c (49.7 %), C16 : 0 (12.0 %) and 11-methyl C18 : 1omega7c (11.5 %), and ubiquinone-10 (Q-10) was the predominant respiratory lipoquinone. The genomic DNA G+C content of strain Yeonmyeong 2-22T was calculated to be 63.0 mol%. Phenotypic characteristics of the novel strain also differed from other members of the genus Porphyrobacter. On the basis of polyphasic taxonomic data, strain Yeonmyeong 2 22Trepresents as a novel species of the genus Porphyrobacter, for which the name of Porphyrobacter algicida sp. nov. is proposed. The type strain is Yeonmyeong 2 22T (=KEMB 9005-328T=JCM 31499T). PMID- 28984559 TI - Ponticoccus marisrubri sp. nov., a moderately halophilic marine bacterium of the family Rhodobacteraceae. AB - Strain SJ5A-1T, a Gram-stain-negative, coccus-shaped, non-motile, aerobic bacterium, was isolated from the brine-seawater interface of the Erba Deep in the Red Sea, Saudi Arabia. The colonies of strain SJ5A-1T have a beige to pale-brown pigmentation, are approximately 0.5-0.7 um in diameter, and are catalase and oxidase positive. Growth occurred optimally at 30-33 degrees C, pH 7.0-7.5, and in the presence of 9.0-12.0 % NaCl (w/v). Phylogenetic analysis of the 16S rRNA gene indicates that strain SJ5A-1T is a member of the genus Ponticoccus within the family Rhodobacteraceae. Ponticoccus litoralis DSM 18986T is the most closely related described species based on 16S rRNA gene sequence identity (96.7 %). The DNA-DNA hybridization value between strain SJ5A-1T and P. litoralis DSM 18986T was 36.7 %. The major respiratory quinone of strain SJ5A-1T is Q-10; it predominantly uses the fatty acids C18 : 1 (54.2 %), C18 : 0 (11.2 %), C16 : 0 (8.6 %), 11-methyl C18 : 1omega7c (7.7 %), C19 : 0cyclo omega8c (3.3 %), and C12 : 1 3-OH (3.5 %), and its major polar lipids are phosphatidylethanolamine, phosphatidylglycerol, phosphocholine, an unknown aminolipid, an unknown phospholipid and two unknown lipids. The genome draft of strain SJ5A-1T as presented here is 4 562 830 bp in size and the DNA G+C content is 68.0 mol%. Based on phenotypic, phylogenetic and genotypic data, strain SJ5A-1T represents a novel species in the genus Ponticoccus, for which we propose the name Ponticoccus marisrubri sp. nov. The type strain of P. marisrubri is SJ5A-1T (=JCM 19520T=ACCC19863T). PMID- 28984560 TI - Kineococcus terrestris sp. nov. and Kineococcus aureolus sp. nov., isolated from saline sediment. AB - Two novel actinobacteria, designated YIM 121936T and YIM 121940T, were isolated from alkaline sediment in Yuanjiang, China. The cells of the novel strains were Gram-stain-positive, aerobic, motile, non-spore-forming and coccus-shaped. The two strains both contained meso-diaminopimelic acid as the diagnostic diamino acid. The whole-cell sugars were arabinose, galactose, glucose, mannose and ribose. The predominant menaquinone was MK-9(H2). The polar lipid profile of both strains comprised diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, phosphatidylinositol mannoside, one unknown phosphoglycolipid and five unknown phospholipids. The predominant fatty acids of both strains were anteiso-C15 : 0. The genomic DNA G+C contents of strains YIM 121936T and YIM 121940T were 74.7 and 75.2 %, respectively. Strain YIM 121936T was closely related to Kineococcus aurantiacus IFO 15268T (97.19 %), Kineococcus gypseus YIM 121300T (97.00 %) and Kineococcus mangrovi NBRC 110933T (97.00 %). Strain YIM 121940T was closely related to K. aurantiacus IFO 15268T (97.41 %), Kineococcus endophytica KLBMP 1274T (97.18 %), Kineococcus rhizosphaerae RP-B16T (97.09 %), Kineococcus radiotolerans SRS 30216T (97.09 %), K. gypseus YIM 121300T (97.00 %) and K. mangrovi NBRC 110933T (97.00 %). Strain YIM 121936T shared high 16S rRNA gene sequence similarity (99 %) with YIM 121940T. Similarities of two strains with other species of the genus Kineococcus were <97 %. The DNA-DNA hybridization values were below 70 % among all the strains studied. YIM 121936T and YIM 121940T are representatives of two new species in the genus Kineococcus, for which names Kineococcus terreus sp. nov. (type strain YIM 121936T=KCTC 39738T=DSM 102155T) and Kineococcus aureolus sp. nov. (type strain YIM 121940T=KCTC 39739T=DSM 102158T) are proposed, respectively. PMID- 28984561 TI - Ciceribacter thiooxidans sp. nov., a novel nitrate-reducing thiosulfate-oxidizing bacterium isolated from sulfide-rich anoxic sediment. AB - Two facultative chemolithotrophic, nitrate-reducing thiosulfate-oxidizing strains, F43bT and F21, were isolated from the sulfide-rich anoxic sediment of an urban creek in Pearl River Delta, China. Both strains were Gram-negative, facultatively anaerobic, non-spore-forming and rod-shaped with a flagellum. Phylogenetic analyses of 16S rRNA genes and the thrC, recA, glnII and atpD housekeeping genes revealed that the type strain shared high sequence similarities to Ciceribacter lividus MSSRFBL1T, with 98.8, 90.9, 94.8, 95.4 and 96.1 % identity, respectively. In addition, the major isoprenoid quinone (ubiquinone Q-10) and the DNA G+C content (66.0 mol%) of the type strain were similar to those of Ciceribacter lividus MSSRFBL1T. These results strongly support the classification of strains F43bT and F21 into the genus Ciceribacter. However, these strains diverged markedly from strain MSSRFBL1T with respect to several physiological and biochemical properties such as their semi-translucent colonies and nitrate-reducing and simultaneous thiosulfate-oxidizing respiration. Furthermore, the predominant fatty acids of strain F43bT were summed feature 2 (C18 : 1omega9t and/or C18 : 1omega9c and/or C18 : 1omega11t), C14 : 0 3-OH, C18 : 0 and C16 : 0, and its polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidymonomethylethanolamine and an unidentified glycolipid, which represented another two significant differences from strain MSSRFBL1T. Importantly, the DNA-DNA relatedness between strain F43bT and MSSRFBL1T was only 47.7 %. Based on the aforementioned polyphasic taxonomic results, the two isolates are suggested to represent a novel species of the genus Ciceribacter, for which the name Ciceribacterthiooxidans sp. nov. is proposed; the type strain is F43bT (=CCTCC AB 2016062T=KCTC 52231T). PMID- 28984563 TI - Flavobacterium limi sp. nov., isolated from forest mud. AB - A Gram-stain-negative, aerobic, non-motile, yellow and rod-shaped bacterial strain was isolated from forest mud located at Kyung Hee University, South Korea. Strain THG-AG6.4T grew at 10-35 degrees C, pH 6.0-9.5 and in the presence of 0 1.5 % (w/v) NaCl. Phylogenetic analysis, based on 16S rRNA gene sequencing, showed that strain THG-AG6.4T was most closely related to Flavobacterium gyeonganense HME 7524T (97.66 %), Flavobacterium defluvii EMB 117T (96.93 %) and Flavobacterium arsenitoxidans S2-3HT (96.80 %). The DNA G+C content of strain THG AG6.4T was 30.2 mol%. The DNA-DNA relatedness values between strain THG-AG6.4T and its closest phylogenetic neighbour, F. gyeonganense HME 7524T, were below 61.0 %. The predominant quinone of strain THG-AG6.4T was MK-6. The major polar lipids were phosphatidylethanolamine, an unidentified phospholipid, five unidentified glycolipids, phosphatidylserine, an unidentified lipid, an unidentified aminophospholipid, two unidentified aminolipids and two unidentified aminoglycolipids. The major fatty acids were C16 : 0, C18 : 0 10-methyl, summed feature 3 and C18 : 1omega9c. The major polyamine was homospermidine. On the basis of the phenotypic, genotypic and phylogenetic characterization of strain THG-AG6.4T, it is concluded that the isolate represents a novel species of the genus Flavobacterium, for which the name Flavobacterium limi sp. nov. is proposed, with THG-AG6.4T as the type strain (=KACC 18851T=CGMCC 1.16060T). PMID- 28984562 TI - Deinococcus taklimakanensis sp. nov., isolated from desert soil. AB - A gamma- and UV radiation-tolerant, Gram-negative, short-rod-shaped bacterial strain, designated X-121T, was isolated from soil samples collected from the Taklimakan desert in Xinjiang, China. Strain X-121T showed the highest 16S rRNA gene sequence similarity with Deinococcus depolymerans TDMA-24T (94.7 %). Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain X 121T is a member of a novel species belonging to the clade formed by members of the genus Deinococcus in the family Deinococcaceae. The DNA G+C content of strain X-121T was 63.6 mol%. The chemotaxonomic charateristics of strain X-121T were typical of members of the genus Deinococcus, with MK-8 being the predominant respiratory quinone, summed feature 3 (16 : 1omega7c,16 : 1omega6c), 16 : 0 and 17 : 1omega8c as major cellular fatty acid, several unidentified phosphoglycolipids and glycolipids as the dominant polar lipids, galactose as the predominant cell-wall sugar and the presence of peptidoglycan with l-ornithine. Strain X-121T is therefore identified as representing a novel species, for which the name Deinococcus taklimakanensis sp. nov. is proposed, with the type strain X 121T(=CCTCC AB 207228T=KCTC 33842T). PMID- 28984564 TI - Sabulilitoribacter arenilitoris sp. nov., isolated from seashore sand. AB - A Gram-stain-negative and non-motile bacterial strain that formed rods and orange pigmented colonies, designated HMF6543T, was isolated from sand of seashore on the South Sea, Republic of Korea. Strain HMF6543T grew optimally at 30 degrees C, at pH 7.0-8.0 and in the presence of 2 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain HMF6543T belonged to the genus Sabulilitoribacter. The most closest related species was Sabulilitoribacter multivorans M-M16T (96.7 %, sequence similarity). Strain HMF6543T contained MK-6 as the predominant menaquinone and iso-C15 : 1 G, iso-C15 : 0 and iso-C17 : 0 3 OH as the major fatty acids. The major polar lipids detected in strain HMF6543T were phosphatidylethanolamine, two unidentified aminolipids, one unidentified glycolipid and three unidentified lipids. The DNA G+C content of strain HMF6543T was 31.9 mol%. On the basis of the evidence presented in this study, strain HMF6543T represents a novel species of the genus Sabulilitoribacter, for which the name Sabulilitoribacterarenilitoris sp. nov. is proposed. The type strain is HMF6543T (=KCTC 52401T=NBRC 112674T). PMID- 28984565 TI - Risk factors for and role of OprD protein in increasing minimal inhibitory concentrations of carbapenems in clinical isolates of Pseudomonas aeruginosa. AB - PURPOSE: This study examined the risk factors for, and molecular mechanisms underlying, the increase in carbapenem minimum inhibitory concentrations (MICs) in clinical isolates of Pseudomonas aeruginosa. METHODOLOGY: Consecutive clinical isolates of P. aeruginosa were collected. The MicroScan WalkAway system detected more than fourfold increases in the MICs of carbapenems in P. aeruginosa isolates serially recovered from some patients during their clinical course. The clinical risk factors associated with this increase were examined by multiple logistic regression analysis. Western blot analysis and nucleotide sequencing of the oprD gene of 19 clonally related and paired P. aeruginosa isolates from the same patients were undertaken to examine the mechanisms underlying the increase in MICs. RESULTS: The results showed that prior use of carbapenems (OR, 2.799; 95 % CI, 1.088-7.200; P=0.033) and the use of ventilators or tracheostomies (OR, 2.648; 95 % CI, 1.051-6.671; P=0.039) were risk factors for increased carbapenem MICs. Analysis of the underlying mechanisms revealed that loss of functional OprD protein due to mutation of the oprD gene tended to occur in P. aeruginosa isolates with imipenem MICs of more than 8 ug ml-1; a reduction in OprD expression was observed in P. aeruginosa isolates with imipenem MICs of 4 or 8 ug ml-1. This difference in the resistance mechanism was not correlated with the MICs of meropenem. CONCLUSION: This difference in the resistance mechanism of P. aeruginosa indicates a critical breakpoint at an imipenem MIC of 8 ug ml-1, in accordance with EUCAST criteria. Reducing carbapenem use will prevent P. aeruginosa clinical isolates from developing resistance to carbapenems. PMID- 28984566 TI - Pertussis-associated persistent cough in previously vaccinated children. AB - To evaluate the role of Bordetella pertussis infection, 96 otherwise healthy 7- to 17-year-old subjects who were suffering from a cough lasting from 2 to 8 weeks were prospectively recruited. At enrolment, a nasopharyngeal swab and an oral fluid sample were obtained to search for pertussis infection by the detection of B. pertussis DNA and/or an elevated titre of anti-pertussis toxin IgG. Evidence of pertussis infection was found in 18 (18.7 %; 95 % confidence interval, 11.5 28.0) cases. In 15 cases, the disease occurred despite booster administration. In two cases, pertussis was diagnosed less than 2 years after the booster injection, whereas in the other cases it was diagnosed between 2 and 9 years after the booster dose. This study used non-invasive testing to show that pertussis is one of the most important causes of long-lasting cough in school-age subjects. Moreover, the protection offered by acellular pertussis vaccines currently wanes more rapidly than previously thought. PMID- 28984567 TI - Polaribacter tangerinus sp. nov., isolated from sediment in a sea cucumber culture pond. AB - A Gram-stain-negative, aerobic, non-motile, coccoid, ovoid or rod-shaped, and orange-pigmented bacterial strain, designated WS2-14T, was isolated from sediment collected from a sea cucumber culture pond located in Rongcheng, Shandong province, PR China (122 degrees 14' E, 36 degrees 54' N). Strain WS2-14T grew optimally at 28 degrees C and pH 7.0-7.5, and was able to tolerate salt concentrations of 0.5-6.0 % (w/v) NaCl. Strain WS2-14T was characterized chemotaxonomically as possessing menaquinone-6 (MK-6) as the major respiratory quinone, as well as iso-C13 : 0, iso-C15 : 0 3-OH and iso-C15 : 0 as the predominant fatty acids. The DNA G+C content of strain WS2-14T was 31.2 mol%. The major polar lipids were phosphatidylethanolamine, one unidentified phospholipid, one unidentified aminolipid and three unidentified lipids. Phylogenetic analyses based on 16S rRNA gene sequences revealed that strain WS2-14T was phylogenetically related to members of the genus Polaribacter and was closely related to Polaribacter haliotis, Polaribacter atrinae and Polaribacter sejongensis with 97.7, 97.4 and 97.0 % sequence similarities, respectively. On the basis of its phenotypic and chemotaxonomic properties, as well as phylogenetic analyses, strain WS2-14T was considered to represent a novel species of the genus Polaribacter, for which the name Polaribactertangerinus sp. nov. is proposed. The type strain is WS2-14T (=KCTC 52275T=MCCC 1H00163T). PMID- 28984568 TI - Bacillus ciccensis sp. nov., isolated from maize (Zea mays L.) seeds. AB - Two Gram-stain-positive bacterial strains, designated as 5L6T and 6L6, isolated from seeds of hybrid maize (Zea mays L., Jingke 968) were investigated using a polyphasic taxonomic approach. The cells were aerobic, motile, endospore-forming and rod-shaped. Phylogenetic analysis based on 16S rRNA gene sequences showed that the isolates were recognized as a species of the genus Bacillus, to which the five closest neighbours are Bacillus solani FJAT-18043T (99.8 % similarity), Bacillus horneckiae DSM 23495T (97.7 %), Bacillus eiseniae A1-2T (97.4 %), Bacillus kochii WCC 4582T (97.1 %) and Bacillus purgationiresistens DS22T (97.0 %). The DNA G+C content of strain 5L6T was 37.4 mol%. Its polar lipid profile consisted of diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine. The predominant respiratory quinone was MK-7 and the major fatty acids were iso-C15 : 0, anteiso-C15 : 0, iso-C16 : 0, iso-C14 : 0, anteiso-C17 : 0 and C16 : 1 omega7c alcohol. The cell-wall peptidoglycan contained ornithine, serine, aspartic acid, glutamic acid and alanine while diaminopimelic acid could not be detected. Strains 5L6T and 6L6 were clearly distinguished from the type strains of related validly named species using phylogenetic analysis, DNA-DNA hybridization, fatty acid analysis, peptidoglycan analysis and comparison of a range of physiological and biochemical characteristics. The genotypic and phenotypic data show that strains 5L6T and 6L6 represent a novel species of the genus Bacillus, for which the name Bacillusciccensis sp. nov. is proposed. The type strain is 5L6T (=KCTC 33663T=CICC 23855T=DSM 104513T). PMID- 28984569 TI - Nonomuraea cavernae sp. nov., a novel actinobacterium isolated from a karst cave sample. AB - A novel actinobacterial strain, designated SYSU K10005T, was isolated from a soil sample collected from a karst cave in Xingyi county, Guizhou province, south-west China. The taxonomic position of the strain was investigated using a polyphasic approach. Cells of the strain were aerobic and Gram-stain-positive. On the basis of 16S rRNA gene sequence analysis, strain SYSU K10005T was most closely related to the type strains of the genus Nonomuraea, and shared highest sequence similarity of 98.4 % with Nonomuraea candida HMC10T. DNA-DNA hybridization values between the two strains were less than 70 %. The whole-cell hydrolysates of strain SYSU K10005T contained meso-diaminopimelic acid (diagnostic diamino acid), and arabinose, madurose and rhamnose (whole-cell sugars). The major isoprenoid quinone was MK-9(H4), while the major fatty acids were iso-C16 : 0, 10-methyl C17 : 0, C17 : 1omega8c and C17 : 0. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, hydroxyl phosphatidylethanolamine, lyso-phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositol mannosides, an unidentified lipid, two unidentified ninhydrin-positive phosphoglycolipids and two unidentified phospholipids. The genomic DNA G+C content of strain SYSU K10005T was 64.2 mol%. On the basis of phenotypic, genotypic and phylogenetic data, strain SYSU K10005T can be characterized to represent a novel species of the genus Nonomuraea, for which the name Nonomuraea cavernae sp. nov. is proposed. The type strain is SYSU K10005T (=KCTC 39805T=CGMCC 4.7368T). PMID- 28984570 TI - Parapedobacter defluvii sp. nov., isolated from the sewage treatment packing of a coking chemical plant. AB - Strain WY-1T, a Gram-stain-negative, non-spore-forming, rod-shaped, non-motile bacterium, was isolated from the sewage treatment packing of a coking chemical plant. Strain WY-1T grew over a temperature range of 15-45 degrees C (optimum, 30-37 degrees C), a pH range of 5.5-11.0 (optimum, pH 6.5-7.0) and an NaCl concentration range of 0-3 % (w/v; optimum, 0 %). 16S rRNA gene sequence analysis showed that strain WY-1T was closely related to Parapedobacter indicus RK1T with the highest sequence similarity of 96.0 %. The predominant cellular fatty acids of the novel strain were iso-C15 : 0, summed feature 3(C16 : 1omega6c and/or C16 : 1omega7c), iso-C17 : 0 3-OH, iso-C17 : 1omega9c, iso-C15 : 0 3-OH and C16 : 0. The respiratory quinone of the cells was menaquinone 7 (MK-7). The main polar lipid was phosphatidylethanolamine, an unidentified phospholipid, two unidentified aminolipids and two unknown lipids. The G+C content of the DNA was 47.1 mol%. Chemotaxonomic characteristics and phylogenetic analyses revealed that strain WY-1T belonged to the genus Parapedobacter. Strain WY-1T showed a range of phenotypic characteristics that differentiated it from species of the genus Parapedobacter with validly published names, including its assimilation from carbon sources, enzyme activities and having a wider pH range for growth. Based on these results, it is concluded that strain WY-1T represents a novel species of the genus Parapedobacter, for which the name Parapedobacter defluvii sp. nov. is proposed. The type strain is WY-1T (=NBRC 112611T=CGMCC 1.15342T). PMID- 28984571 TI - Characterization of Marinomonas algicida sp. nov., a novel algicidal marine bacterium isolated from seawater. AB - A novel Marinomonas-like, aerobic, Gram-reaction-negative, moderately halophilic, acidophilic, motile by a single polar flagellum, non-spore-forming, rod-shaped bacterium that showed algalytic activity, designated strain Yeongu 1-4T, was isolated from surface seawater of Geoje Island in the South Sea, Republic of Korea. The strain was oxidase-negative and weakly positive for catalase. Growth of this bacterium was observed at temperatures from 4 to 42 degrees C, at salinities from 0 to 12 % and at pH from 4.5 to 9.0, and it was not able to degrade starch, gelatin, casein or Tween 80. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain Yeongu 1-4T was related most closely to Marinomonas spartinae SMJ19T with similarity of 99.3 %. However, levels of DNA DNA relatedness between strain Yeongu 1-4T and the most closely related species were lower than 70 %, confirming that they represent distinct genomic species. The genomic DNA G+C content of strain Yeongu 1-4T was 44.2 mol%. The organism used Q-8 as the predominant respiratory quinone, and C16 : 1omega7c, C18 : 1omega7c and C16 : 0 as major cellular fatty acids. Based on data from this polyphasic taxonomic study, strain Yeongu 1-4T belongs to a novel species of the genus Marinomonas, within the family Oceanospirillaceae, for which the name Marinomonas algicida is proposed. The type strain is Yeongu 1-4T (=KEMB 9005 327T=MCCC 1K00609T). PMID- 28984572 TI - Total hip arthroplasty via the direct anterior approach with a dual mobility cup for displaced femoral neck fracture in patients with a high risk of dislocation. AB - INTRODUCTION: Although total hip arthroplasty (THA) is superior to bipolar hemiarthroplasty (BHA) for displaced femoral neck fracture in terms of hip pain, function and reoperation rate, THA has a higher rate of dislocation. The direct anterior approach (DAA) and a dual mobility cup (DMC) are associated with lower rates of dislocation. The aim of this study was to investigate the outcomes of THA compared with BHA, and in those patients who had a THA we investigated those with a DMC (DMC-THA) and compared them with those had a single conventional cup (Single cup-THA). MATERIALS: A total of 89 patients living independently were included between 2009 and 2015. We assessed patient characteristics, peri- and post-operative outcomes, walking ability and one-year mortality. Adjusted odds ratios (Adjusted ORs) were estimated for decrease of walking ability and one-year mortality using a logistic regression model with adjustment for potential confounders such as age, neuromuscular diseases with weakness, duration of surgery, perioperative blood loss and preoperative walking ability. RESULTS: BHA (20 patients) versus THA (69 patients): There was no significant difference in the walking ability in either group. Multivariable logistic regression analysis demonstrated a significant association with one-year mortality in both groups [THA Adjusted ORs 0.088 (95% CI 0.0007-0.69); p = 0.020]. Single cup-THA (36 patients) versus DMC-THA (33 patients): The DMC-THA group had significantly greater age and more patients with neuromuscular diseases with weakness compared with the Single cup-THA group. Multivariable logistic regression analysis demonstrated no significant difference in the decrease of walking ability and in the one-year mortality between the groups. There were no post operative dislocations in any group. DISCUSSION: THA via the DAA is one of the best treatments for displaced femoral neck fracture with a low risk of dislocation. THA via the DAA with a DMC is a safe and effective treatment for the patients with a high risk of dislocation. PMID- 28984573 TI - Sleep homeostasis regulated by 5HT2b receptor in a small subset of neurons in the dorsal fan-shaped body of drosophila. AB - Our understanding of the molecular mechanisms underlying sleep homeostasis is limited. We have taken a systematic approach to study neural signaling by the transmitter 5-hydroxytryptamine (5-HT) in drosophila. We have generated knockout and knockin lines for Trh, the 5-HT synthesizing enzyme and all five 5-HT receptors, making it possible for us to determine their expression patterns and to investigate their functional roles. Loss of the Trh, 5HT1a or 5HT2b gene decreased sleep time whereas loss of the Trh or 5HT2b gene diminished sleep rebound after sleep deprivation. 5HT2b expression in a small subset of, probably a single pair of, neurons in the dorsal fan-shaped body (dFB) is functionally essential: elimination of the 5HT2b gene from these neurons led to loss of sleep homeostasis. Genetic ablation of 5HT2b neurons in the dFB decreased sleep and impaired sleep homeostasis. Our results have shown that serotonergic signaling in specific neurons is required for the regulation of sleep homeostasis. PMID- 28984575 TI - To rebound or not to rebound. AB - Sexual arousal in flies counteracts the effects of sleep deprivation. PMID- 28984576 TI - Ground state properties of 3d metals from self-consistent GW approach. AB - The self consistent GW approach (scGW) has been applied to calculate the ground state properties (equilibrium Wigner-Seitz radius S WZ and bulk modulus B) of 3d transition metals Sc, Ti, V, Fe, Co, Ni, and Cu. The approach systematically underestimates S WZ with average relative deviation from the experimental data of about 1% and it overestimates the calculated bulk modulus with relative error of about 25%. It is shown that scGW is superior in accuracy as compared to the local density approximation but it is less accurate than the generalized gradient approach for the materials studied. If compared to the random phase approximation, scGW is slightly less accurate, but its error for 3d metals looks more systematic. The systematic nature of the deviation from the experimental data suggests that the next order of the perturbation theory should allow one to reduce the error. PMID- 28984574 TI - Ligand modulation of sidechain dynamics in a wild-type human GPCR. AB - GPCRs regulate all aspects of human physiology, and biophysical studies have deepened our understanding of GPCR conformational regulation by different ligands. Yet there is no experimental evidence for how sidechain dynamics control allosteric transitions between GPCR conformations. To address this deficit, we generated samples of a wild-type GPCR (A2AR) that are deuterated apart from 1H/13C NMR probes at isoleucine delta1 methyl groups, which facilitated 1H/13C methyl TROSY NMR measurements with opposing ligands. Our data indicate that low [Na+] is required to allow large agonist-induced structural changes in A2AR, and that patterns of sidechain dynamics substantially differ between agonist (NECA) and inverse agonist (ZM241385) bound receptors, with the inverse agonist suppressing fast ps-ns timescale motions at the G protein binding site. Our approach to GPCR NMR creates a framework for exploring how different regions of a receptor respond to different ligands or signaling proteins through modulation of fast ps-ns sidechain dynamics. PMID- 28984577 TI - Ultraviolet-assisted direct patterning and low-temperature formation of flexible ZrO2 resistive switching arrays on PET/ITO substrates. AB - We demonstrate a low-cost and facile photochemical solution method to prepare the ZrO2 resistive switching arrays as memristive units on flexible PET/ITO substrates. ZrO2 solution sensitive to UV light of 337 nm was synthesized using zirconium n-butyl alcohol as the precursor, and benzoylacetone as the complexing agent. After the dip-coated ZrO2 gel films were irradiated through a mask under the UV lamp (with wavelength of 325-365 nm) at room temperature and rinsed in ethanol, the ZrO2 gel arrays were obtained on PET/ITO substrates. Subsequently, the ZrO2 gel arrays were irradiated by deep UV light of 254 and 185 nm at 150 degrees C, resulting in the amorphous ZrO2 memristive micro-arrays. The ZrO2 units on flexible PET/ITO substrates exhibited excellent memristive properties. A high ratio of 104 of on-state and off-state resistance was obtained. The resistive switching behavior of the flexible device remained stable after being bent for 103 times. The device showed stable flexibility up to a minimum bending diameter of 1.25 cm. PMID- 28984578 TI - Process-specific analysis in episodic memory retrieval using fast optical signals and hemodynamic signals in the right prefrontal cortex. AB - OBJECTIVE: Memory is formed by the interaction of various brain functions at the item and task level. Revealing individual and combined effects of item- and task related processes on retrieving episodic memory is an unsolved problem because of limitations in existing neuroimaging techniques. To investigate these issues, we analyze fast and slow optical signals measured from a custom-built continuous wave functional near-infrared spectroscopy (CW-fNIRS) system. APPROACH: In our work, we visually encode the words to the subjects and let them recall the words after a short rest. The hemodynamic responses evoked by the episodic memory are compared with those evoked by the semantic memory in retrieval blocks. In the fast optical signal, we compare the effects of old and new items (previously seen and not seen) to investigate the item-related process in episodic memory. The Kalman filter is simultaneously applied to slow and fast optical signals in different time windows. MAIN RESULTS: A significant task-related HbR decrease was observed in the episodic memory retrieval blocks. Mean amplitude and peak latency of a fast optical signal are dependent upon item types and reaction time, respectively. Moreover, task-related hemodynamic and item-related fast optical responses are correlated in the right prefrontal cortex. SIGNIFICANCE: We demonstrate that episodic memory is retrieved from the right frontal area by a functional connectivity between the maintained mental state through retrieval and item-related transient activity. To the best of our knowledge, this demonstration of functional NIRS research is the first to examine the relationship between item and task-related memory processes in the prefrontal area using single modality. PMID- 28984579 TI - Follow-up of patients undergoing oncoplastic surgery - more palpable masses and benign biopsies. AB - BACKGROUND: Oncoplastic reconstruction is increasingly used in the management of women undergoing breast conserving surgery. We examined the findings on breast exam and imaging of patients who underwent breast conservation with or without oncoplastic reconstruction. OBJECTIVE: We hypothesized that patients undergoing immediate breast reconstruction would present with more palpable and imaging abnormalities compared to lumpectomy alone and undergo therefore more biopsies. METHODS: All patients undergoing breast conservation with oncoplastic reconstruction for breast cancer between 2009 and 2014 were included in the study group. The control group was created by matching 4 women that underwent lumpectomy alone during the same week to each patient in the study group. The two groups were compared regarding demographics, tumor characteristics, post operative complaints, breast exam, imaging and biopsies done during follow-up. RESULTS: The study group included 67 women who had lumpectomy and immediate oncoplastic reconstruction and 268 women that underwent lumpectomy alone.Patients undergoing immediate oncoplastic reconstruction had more advanced disease; larger mean tumor size (3.1 cm versus 1.9 cm, P < 0.001), higher rate of involved lymph nodes (48% versus 26%; P < 0.001) and use of neoadjuvant treatment (39% versus 15%; P < 0.001).After oncoplastic reconstruction, new lumps (18% versus 5%; P = 0.004) were found more frequently, and there was a higher rate of women undergoing biopsies (31% versus 11%; P < 0.001). This finding remained significant after controlling for age, type of tumor, use of neoadjuvant treatment and volume of tissue removed. Over ninety percent of biopsies in the oncoplastic group were benign, most commonly-fat necrosis (N = 15, 60% of the biopsies). CONCLUSIONS: Immediate oncoplastic reconstruction is associated with increased palpable masses and imaging abnormalities, requiring biopsies. Patients and clinicians should be aware of the benign nature of most of these findings. PMID- 28984580 TI - Memory Complaints and Cognitive Decline: Data from the GUIDAGE Study1. AB - BACKGROUND: Subjective cognitive decline (SCD) may be a very early symptom of Alzheimer's disease (AD) and may be associated with a cognitive decline in a cognitively normal population. The McNair and Kahn Scale was used to assess memory complaints in the GuidAge study. OBJECTIVE: Our objectives were to examine if the McNair and Kahn Scale can predict cognitive decline and to screen which (if any) of the question(s) of this scale would better predict this cognitive decline. METHODS: The GuidAge study was a phase III, multicenter, randomized, double blind, placebo-controlled study. Individuals aged 70 years and older, without cognitive impairment (Clinical Dementia Rate (CDR = 0)) at baseline who had spontaneously reported SCD were included in this study. The 20-item version of the McNair and Kahn Scale was used to assess SCD and a standardized neuropsychological assessment was used to assess the cognitive status. RESULTS: 1,307 patients with SCD and with CDR = 0 at baseline were included. During the 5 years of follow-up, 519 patients showed cognitive decline. Incidence of aggravation score of CDR was 13.40% person years (95% CI [12.24-14.56]). Results showed a significant relationship between the McNair and Kahn Scale score and decline in cognitive performance (HR 1.012; 95% CI [1.002-1.021]; p = 0.0156). Among the 20 items, 5 were statistically significant to predict cognitive decline after adjustment. CONCLUSION: SCD is a promising indicator of memory impairment. Our study found that using the McNair and Kahn scale can predict cognitive decline. A 5-item version of this scale could be used to screen patients in clinical practice and in clinical research. PMID- 28984581 TI - Screening for Alzheimer's Disease: Cognitive Impairment in Self-Referred and Memory Clinic-Referred Patients. AB - BACKGROUND: Cognitive assessment is essential in tracking disease progression in AD. Presently, cohorts including preclinical at-risk participants are recruited by different means, which may bias cognitive and clinical features. We compared recruitment strategies to levels of cognitive functioning. OBJECTIVE: We investigate recruitment source biases in self-referred and memory clinic-referred patient cohorts to reveal potential differences in cognitive performance and demographics among at-risk participants. METHODS: We included 431 participants 40 80 years old. Participants were classified as controls (n = 132) or symptom group (n = 299). The symptom group comprised of subjective cognitive decline (SCD, n = 163) and mild cognitive impairment (MCI, n = 136). We compared cognitive performance and demographics in memory clinic-referrals (n = 86) to self-referred participants responding to advertisements and news bulletins (n = 179). Participants recruited by other means were excluded from analysis (n = 34). RESULTS: At symptom group level, we found significant reductions in cognitive performance in memory clinic-referrals compared to self-referrals. However, here reductions were only found within the MCI group. We found no differences in cognitive performance due to recruitment within the SCD group. The MCI group was significantly impaired compared to controls on all measures. Significant reductions in learning, and executive functions were also found for the SCD group. CONCLUSION: Regardless of recruitment method, both the SCD and MCI groups showed reductions in cognitive performance compared to controls. We found differences in cognitive impairment for memory clinic-referrals compared to self referrals only within the MCI group, SCD-cases being equally affected irrespective of referral type. PMID- 28984584 TI - Perception and Reality of Cognitive Function: Information Processing Speed, Perceived Memory Function, and Perceived Task Difficulty in Older Adults. AB - This study examines the relationships between two measures of information processing speed associated with executive function (Trail Making Test and a computer-based visual search test), the perceived difficulty of the tasks, and perceived memory function (measured by the Memory Functioning Questionnaire) in older adults (aged 50+ y) with normal general health, cognition (Montreal Cognitive Assessment score of 26+), and mood. The participants were recruited from the community rather than through clinical services, and none had ever sought or received help from a health professional for a memory complaint or mental health problem. For both the trail making and the visual search tests, mean information processing speed was not correlated significantly with perceived memory function. Some individuals did, however, reveal substantially slower information processing speeds (outliers) that may have clinical significance and indicate those who may benefit most from further assessment and follow up. For the trail making, but not the visual search task, higher levels of subjective memory dysfunction were associated with a greater perception of task difficulty. The relationship between actual information processing speed and perceived task difficulty also varied with respect to the task used. These findings highlight the importance of taking into account the type of task and metacognition factors when examining the integrity of information processing speed in older adults, particularly as this measure is now specifically cited as a key cognitive subdomain within the diagnostic framework for neurocognitive disorders. PMID- 28984583 TI - Deficit in Central Auditory Processing as a Biomarker of Pre-Clinical Alzheimer's Disease. AB - Prevention of dementia due to Alzheimer's disease (d/AD) requires interventions that slow the disease process prior to symptom onset. To develop such interventions, one needs metrics that assess pre-symptomatic disease progression. Familiar measures of progression include cerebrospinal fluid (CSF) biochemical and imaging analyses, as well as cognitive testing. Changes in the latter can sometimes be difficult to distinguish from effects of "normal" aging. A different approach involves testing of "central auditory processing" (CAP), which enables comprehension of auditory stimuli amidst a distracting background (e.g., conversation in a noisy bar or restaurant). Such comprehension is often impaired in d/AD. Similarly, effortful or diminished auditory comprehension is sometimes reported by cognitively healthy elders, raising the possibility that CAP deficit may be a marker of pre-symptomatic AD. In 187 cognitively and physically healthy members of the aging, AD family history-positive PREVENT-AD cohort, we therefore evaluated whether CAP deficits were associated with known markers of AD neurodegeneration. Such markers included CSF tau concentrations and magnetic resonance imaging volumetric and cortical thickness measures in key AD-related regions. Adjusting for age, sex, education, pure-tone hearing, and APOEE4 status, we observed a persistent relationship between CAP scores and CSF tau levels, entorhinal and hippocampal cortex volumes, cortical thickness, and deficits in cognition (Repeatable Battery for Assessment of Neuropsychological Status total score, and several of its index scales). These cross-sectional observations suggest that CAP may serve as a novel metric for pre-symptomatic AD pathogenesis. They are therefore being followed up longitudinally with larger samples. PMID- 28984585 TI - Memory Correlates of Alzheimer's Disease Cerebrospinal Fluid Markers: A Longitudinal Cohort Study. AB - BACKGROUND: Performance on episodic, semantic, and working memory tests is impaired in Alzheimer's disease (AD)-type dementia, but it is unclear which type of memory test is most strongly associated with early AD biomarkers in cerebrospinal fluid (CSF), and most useful for monitoring disease progression. OBJECTIVE: To examine the association between amyloid-beta 1-42 (Abeta42) and tau in CSF with performance on different memory domains at baseline, and how these CSF markers are related with memory decline. METHODS: We included 263 individuals with normal cognition, mild cognitive impairment, AD-type dementia, and non-AD dementia from the European EDAR study. Assessment included CSF Abeta42 and t-tau analyses with INNO-BIA AlzBio3 Luminex assay, the CERAD wordlist learning and delayed recall, animal fluency test, and the CANTAB Paired Associates Learning (PAL) and Spatial Working Memory tasks. Follow-up assessments were performed within 3 years after baseline. RESULTS: At baseline, decreased CSF Abeta42 correlated most strongly with the PAL total errors adjusted and the wordlist delayed recall and increased CSF t-tau with the wordlist delayed recall. Over time, decreased CSF Abeta42 was associated with decline on the wordlist learning, whereas increased CSF t-tau were associated with decline in scores on the wordlist learning, wordlist delayed recall, and animal fluency. Associations were independent of baseline diagnosis. CONCLUSION: Tests assessing episodic verbal and visuospatial memory are most useful for detection of AD pathology. Tests for episodic verbal memory and semantic memory are most useful for tracking memory decline. PMID- 28984586 TI - Utility of Molecular and Structural Brain Imaging to Predict Progression from Mild Cognitive Impairment to Dementia. AB - This project compares three neuroimaging biomarkers to predict progression to dementia in subjects with mild cognitive impairment (MCI). Eighty-eight subjects with MCI and 40 healthy controls (HCs) were recruited. Subjects had a 3T magnetic resonance imaging (MRI) scan, and two positron emission tomography (PET) scans, one with Pittsburgh compound B ([11C]PIB) and one with fluorodeoxyglucose ([18F]FDG). MCI subjects were followed for up to 4 y and progression to dementia was assessed on an annual basis. MCI subjects had higher [11C]PIB binding potential (BPND) than HCs in multiple brain regions, and lower hippocampus volumes. [11C]PIB BPND, [18F]FDG standard uptake value ratio (SUVR), and hippocampus volume were associated with time to progression to dementia using a Cox proportional hazards model. [18F]FDG SUVR demonstrated the most statistically significant association with progression, followed by [11C]PIB BPND and then hippocampus volume. [11C]PIB BPND and [18F]FDG SUVR were independently predictive, suggesting that combining these measures is useful to increase accuracy in the prediction of progression to dementia. Hippocampus volume also had independent predictive properties to [11C]PIB BPND, but did not add predictive power when combined with the [18F]FDG SUVR data. This work suggests that PET imaging with both [11C]PIB and [18F]FDG may help to determine which MCI subjects are likely to progress to AD, possibly directing future treatment options. PMID- 28984587 TI - Diabetes is Not Associated with Alzheimer's Disease Neuropathology. AB - BACKGROUND: Previous evidence linking diabetes to Alzheimer's disease (AD) neuropathology is mixed and scant data are available from low- and middle-income countries. OBJECTIVE: To investigate the association between diabetes and AD neuropathology in a large autopsy study of older Brazilian adults. METHODS: In this cross-sectional study, diabetes was defined by diagnosis during life or use of antidiabetic medication. A standardized neuropathological examination was performed using immunohistochemistry. The associations of diabetes with Consortium to Establish and Registry for Alzheimer Disease (CERAD) scores for neuritic plaques and Braak-Braak (BB) scores for neurofibrillary tangles were investigated using multivariable ordinal logistic regression. We investigated effect modification of education, race, and APOE on these associations. RESULTS: Among 1,037 subjects (mean age = 74.4+/-11.5 y; mean education = 4.0+/-3.7 y; 48% male, 61% White), diabetes was present in 279 subjects. Diabetes was not associated with BB (OR = 1.12, 95% CI = 0.81-1.54, p = 0.48) or with CERAD (OR = 0.97, 95% CI = 0.68-1.38, p = 0.86) scores on analyses adjusted for sociodemographic and clinical variables. We observed effect modification by the APOE allele E4 on the association between diabetes mellitus and BB scores. CONCLUSION: No evidence of an association between diabetes and AD neuropathology was found in a large sample of Brazilians; however, certain subgroups, such as APOE allele E4 carriers, had higher odds of accumulation of neurofibrillary tangles. PMID- 28984588 TI - Secular Trends in the Incidence of Dementia in a Multi-Ethnic Community. AB - BACKGROUND: Determination of secular trends in cognitive aging is important for prioritization of resources, services, and research in aging populations. Prior studies have identified declining dementia incidence associated with changes in cardiovascular risk factors and increased educational attainment. However, few studies have examined these factors in multi-ethnic cohorts. OBJECTIVE: To identify secular trends in the incidence rate of dementia in an elderly population. METHODS: Participants in this study were drawn from the Washington Heights-Inwood Columbia Aging Project, a multi-ethnic cohort study of northern Manhattan residents aged 65 years and older. Cox proportional hazards models were used to examine differences in the incidence of dementia in cohorts recruited in 1992 and 1999, with age at dementia or age at last follow-up visit as the "time to-event" variable. RESULTS: Overall, there was a 41% reduction in the hazard ratio for dementia among participants in the 1999 cohort compared with those in the 1992 cohort, adjusting for age, sex, race, and baseline memory complaints (HR = 0.59). The reduction in incidence was greatest among non-Hispanic Whites and African-Americans and lowest among Hispanic participants (HRs = 0.60, 0.52 and 0.64, respectively), and was associated with increases in level of educational attainment, especially among African-Americans. Reduction in incidence of dementia was also greater among persons 75 years or older than among younger participants (HR = 0.52 versus HR = 0.69). CONCLUSIONS: Our results support previous findings that secular trends in dementia incidence are changing, including in aging minority populations. PMID- 28984589 TI - Dementia Prevalence in a Rural Region of South Africa: A Cross-Sectional Community Study. AB - BACKGROUND: Dementia is a growing concern for low- and middle-income countries where longevity is increasing and service provision is poor. Global prevalence estimates vary from 2% to 8.5% for those aged 60 years and older. There have been few dementia studies in sub-Saharan Africa, and prevalence data are lacking for South Africa. OBJECTIVE: To conduct a large dementia prevalence study in a low income rural population in South Africa. METHODS: 1,394 Xhosa-speaking community dwellers, aged >=60 y (mean age+/-sd 71.3+/-8.3 y), in three clinic catchment areas, were screened at home. Trained community health workers administered the brief Community Screening Instrument for Dementia (CSID) to participants and informants to assess cognitive and functional capacity. Depressive symptoms were assessed with three questions from the EURO-D. RESULTS: The prevalence estimate using published CSID sensitivity/specificity values was 0.8 (95% CI: 0.06-0.09). Using CSID cut-off scores the estimated prevalence was 0.12 (95% CI: 0.10-0.13), with 161 screen-positives. Both methods gave a rate of 0.11 (95% CI: 0.09-0.13) for those over 65 years (n = 1051). 68.6% of participants were female and 69.8% had less than 7 years of education. Dementia risk was associated with older age and symptoms of depression, but not with sex. The association with education was not significant when controlled for by age. CONCLUSIONS: Dementia prevalence estimates were higher than expected for this low-income rural community. There is a need for increased dementia awareness and feasible support interventions. We also need further studies of regional prevalences, dementia subtypes, and modifiable risk factors in South Africa. PMID- 28984590 TI - Disinhibition in Alzheimer's Disease is Associated with Reduced Right Frontal Pole Cortical Thickness. AB - Neuropsychiatric symptoms in Alzheimer's disease are among the most disabling and difficult aspects for caregivers and treating health professionals to manage. Despite the high prevalence of these behaviors, little is known about the factors which lead some patients to develop florid behavioral symptoms while others may progress to severe dementia without such phenomenon. We examined whether regional brain volumes as measured by cortical thickness would predict the presence or absence of disinhibition in patients with Alzheimer's disease. Using data from the ADNI, we identified 758 patients with caregiver ratings on the Neuropsychiatric Inventory and a volumetric MRI scan with cortical thickness measurements completed in FreeSurfer by the UCSF core. Of these, 177 patients were found to have disinhibition. Logistic regression models demonstrated that reduced cortical thickness in the right frontal pole was associated with the presence of disinhibition even when controlling for age, disease severity, total intracranial volume, gender, and APOE genotype. The results are considered in the context of leading models of the functions of frontopolar cortex. PMID- 28984591 TI - Curcumin Inhibits Tau Aggregation and Disintegrates Preformed Tau Filaments in vitro. AB - The pathological aggregation of tau is a common feature of most of the neuronal disorders including frontotemporal dementia, Parkinson's disease, and Alzheimer's disease. The inhibition of tau aggregation is considered to be one of the important strategies for treating these neurodegenerative diseases. Curcumin, a natural polyphenolic molecule, has been reported to have neuroprotective ability. In this work, curcumin was found to bind to adult tau and fetal tau with a dissociation constant of 3.3+/-0.4 and 8+/-1 MUM, respectively. Molecular docking studies indicated a putative binding site of curcumin in the microtubule-binding region of tau. Using several complementary techniques, including dynamic light scattering, thioflavin S fluorescence, 90 degrees light scattering, electron microscopy, and atomic force microscopy, curcumin was found to inhibit the aggregation of tau. The dynamic light scattering analysis and atomic force microscopic images revealed that curcumin inhibits the oligomerization of tau. Curcumin also disintegrated preformed tau oligomers. Using Far-UV circular dichroism, curcumin was found to inhibit the beta-sheets formation in tau indicating that curcumin inhibits an initial step of tau aggregation. In addition, curcumin inhibited tau fibril formation. Furthermore, the effect of curcumin on the preformed tau filaments was analyzed by atomic force microscopy, transmission electron microscopy, and 90 degrees light scattering. Curcumin treatment disintegrated preformed tau filaments. The results indicated that curcumin inhibited the oligomerization of tau and could disaggregate tau filaments. PMID- 28984592 TI - TOMM40 and APOE Gene Expression and Cognitive Decline in Japanese Alzheimer's Disease Subjects. AB - BACKGROUND: TOMM40 is located on chromosome 19, is in linkage disequilibrium with apolipoprotein E (APOE), andis reported in several genome-wide association studies to be associated with Alzheimer's disease (AD). OBJECTIVE: Assess APOE and TOM40 and mitochondrial genes as blood biomarkers for AD. METHODS: We examined TOMM40, PTEN-induced putative kinase 1 (PINK1), Parkin RBR E3 ubiquitin protein ligase (PARK2), and APOE mRNA expression in relation to the methylation rates of CpG sites in the upstream region of TOMM40exon 1 in peripheral leukocytes and TOMM40523 polyT genotypes in 60 AD and age- and sex-matched control subjects. RESULTS: TOMM40 mRNA expression was significantly lower in AD subjects (0.87+/-0.18 versus 1.0+/-0.23, p = 0.005), and PINK1 mRNA expression was higher in AD subjects (1.5+/-0.61 versus 1.0+/-0.52, p < 0.001). TOMM40 mRNA expression was significantly correlated with the Mini-Mental State Examination total score (r = 0.290, p = 0.027). There was no expressional change in peripheral APOE mRNA in either AD or control subjects (p = 0.32). Methylation rates in the upstream region of TOMM40exon 1 were not different between AD and control subjects (average rate: 1.37+/-0.99 versus 1.39+/-1.20, p = 0.885), and TOMM40523 polyT genotypes were also not different between AD and control subjects (p = 0.67). CONCLUSION: TOMM40 mRNA expression was lower in AD subjects and was correlated with cognitive decline. Significant changes in both TOMM40 and PINK1 mRNA may be related to mitochondrial dysfunction. PMID- 28984593 TI - Exploring Erythrocytes as Blood Biomarkers for Alzheimer's Disease. AB - Peripheral biomarkers for dementia are few and far between. Despite research into blood plasma/serum biomarkers for dementia diagnostics, there is a lack of information on erythrocytes and their vast proteomes as potential biomarkers. This review identifies a number of relevant and potentially promising erythrocyte biomarkers for various subtypes of dementia. These include erythrocyte morphology, oxidative stress, and erythrocyte membrane proteins such as the glucose transporter (GLUT-1), amyloid-beta, IgG, Hsp90, calpain-1, and band 3 protein. Of those proteins identified Hsp90, amyloid-beta, calpain-1 and band 3 show the most promise as pre-clinical biomarkers. However, the most intriguing aspect of erythrocytes is their changed morphology in dementia. The altered morphology not only could be used as a diagnostic biomarker but may be crucial in early pathogenesis of the disease. Further work must be done to establish the pathological connection between the periphery and central disease processes. PMID- 28984582 TI - Multiple System Atrophy: An Oligodendroglioneural Synucleinopathy1. AB - Multiple system atrophy (MSA) is an orphan, fatal, adult-onset neurodegenerative disorder of uncertain etiology that is clinically characterized by various combinations of parkinsonism, cerebellar, autonomic, and motor dysfunction. MSA is an alpha-synucleinopathy with specific glioneuronal degeneration involving striatonigral, olivopontocerebellar, and autonomic nervous systems but also other parts of the central and peripheral nervous systems. The major clinical variants correlate with the morphologic phenotypes of striatonigral degeneration (MSA-P) and olivopontocerebellar atrophy (MSA-C). While our knowledge of the molecular pathogenesis of this devastating disease is still incomplete, updated consensus criteria and combined fluid and imaging biomarkers have increased its diagnostic accuracy. The neuropathologic hallmark of this unique proteinopathy is the deposition of aberrant alpha-synuclein in both glia (mainly oligodendroglia) and neurons forming glial and neuronal cytoplasmic inclusions that cause cell dysfunction and demise. In addition, there is widespread demyelination, the pathogenesis of which is not fully understood. The pathogenesis of MSA is characterized by propagation of misfolded alpha-synuclein from neurons to oligodendroglia and cell-to-cell spreading in a "prion-like" manner, oxidative stress, proteasomal and mitochondrial dysfunction, dysregulation of myelin lipids, decreased neurotrophic factors, neuroinflammation, and energy failure. The combination of these mechanisms finally results in a system-specific pattern of neurodegeneration and a multisystem involvement that are specific for MSA. Despite several pharmacological approaches in MSA models, addressing these pathogenic mechanisms, no effective neuroprotective nor disease-modifying therapeutic strategies are currently available. Multidisciplinary research to elucidate the genetic and molecular background of the deleterious cycle of noxious processes, to develop reliable biomarkers and targets for effective treatment of this hitherto incurable disorder is urgently needed. PMID- 28984594 TI - Alzheimer's Disease: The Alternative Serotonergic Hypothesis of Cognitive Decline. AB - The pathognomonic feature of Alzheimer's disease is a loss of declarative memory. This has generally been attributed to early involvement of medial temporal lobe structures with neurofibrillary tangles and loss of neurons in the entorhinal cortex. However, there has been a re-emerging emphasis on the causal role of brainstem monoaminergic nuclei as involvement of the cholinergic basal forebrain loses prominence. The rejection of this latter theory of cognitive decline is related to inconsistencies in time course and modest effects of treatment using cholinergic agents. The amyloid hypothesis of cortical dysfunction is also losing favor as current trials of plaque dissolution are proving again disappointing. Recent pre-clinical studies on APP/PS1 (familial Alzheimer's disease) transgenic mouse models using serotonergic receptor modulating agents, demonstrate clear neuroprotective effects. The involvement of midbrain raphe in the earliest stages of dementia requires a reassessment of relevant pathophysiology beyond behavioral and affective dimensions. Indeed, a theory of serotonergic modulation of explicit memory formation by direct enhancement of synaptic strength could change the view of the role of these nuclei in AD and lead to more effective treatments. PMID- 28984596 TI - Low Erythrocyte Levels of Proteasome and Acyl-Peptide Hydrolase (APEH) Activities in Alzheimer's Disease: A Sign of Defective Proteostasis? AB - Alzheimer's disease (AD) is a progressive, multifactorial neurodegenerative disorder that is the main cause of dementia. To date, there are no definitive diagnostic tests that can predict or assess onset and progression of the disease. Blood biomarkers for AD are being sought for many years but their identification remains a challenging task. In this study, we investigated the potential relationship between AD and levels of acyl-peptide hydrolase (APEH) and proteasome in erythrocyte samples of 52 participants (26 AD and 26 cognitively healthy controls). A statistically significant decrease in proteasome and exopeptidase/endopeptidase APEH activities was found in AD samples compared to those of healthy controls. Moreover, in contrast to what was observed for proteasome transcripts, APEH activities reduction in AD patients was unrelated to its gene expression levels, suggesting the occurrence of posttranslational modifications or the expression of endogenous inhibitors that might impair enzyme activity. These preliminary data further support a relationship between the APEH proteasome system and AD molecular players, providing the first evidence of its potential use as a novel blood-based indicator for the routine detection of AD. PMID- 28984595 TI - Low Prevalence and Clinical Effect of Vascular Risk Factors in Early-Onset Alzheimer's Disease. AB - BACKGROUND: Determinants of early-onset Alzheimer's disease (EOAD) are not well known. In late-onset AD, vascular risk factors (VRFs) are associated with earlier clinical manifestation. OBJECTIVE: The objective of this study was to assess the putative association between VRFs and EOAD. METHODS: We studied participants with dementia meeting criteria for EOAD (recruited into the French CoMAJ prospective cohort study from 1 June 2009 to 28 February 2014) and age-, gender-matched controls (ratio 1:3, drawn randomly from the French MONA-LISA population-based survey between 2005 and 2007). Demographic data, VRFs, comorbidities, treatments, and APOE genotypes were compared in multivariable logistic regression analyses. RESULTS: We studied 102 participants with dementia (mean+/-standard deviation age: 59.5+/-3.8; women: 59.8%) and 306 controls. Compared with controls, EOAD participants had spent less time in formal education (9.9+/-2.9 versus 11.7+/-3.8 y; p < 0.0001), were less likely to be regular alcohol consumers (p < 0.0001), had a lower body mass index (-2 kg/m2; p < 0.0004), and a lower mean systolic blood pressure (-6.2 mmHg; p = 0.0036). The prevalence of APOE E4 allele was higher in participants with dementia than in controls (50% versus 29.4%; p = 0.0002), as was the prevalence of depression (48% versus 32%; p < 0.001). Similar results were observed in multivariable analysis. Compared with EOAD participants lacking VRFs, EOAD participants with at least one VRF had a higher prevalence of depression (29.6% versus 53.3%, respectively; p = 0.03). CONCLUSION: The prevalence of VRFs is not elevated in EOAD patients (in contrast to older AD patients). Extensive genetic testing should be considered more frequently in the context of EOAD. PMID- 28984597 TI - Cognitive Change in Rehabilitation Patients with Dementia: Prevalence and Association with Rehabilitation Success. AB - BACKGROUND: Dementia is a frequent diagnosis in geriatric rehabilitation. Studies in patients with dementia on the development of their cognitive status during rehabilitation and its relation to functional outcomes have been scarce. OBJECTIVES: To describe the changes in cognitive status in patients with dementia during inpatient rehabilitation and to determine its association with patient characteristics and rehabilitation outcome. METHODS: Cohort study in a geriatric rehabilitation center with data collection at admission and discharge. Outcome measures were change in global and domain-related cognitive functioning and its association with activities of daily living (ADL) and discharge home. RESULTS: 154 patients (mean age 83.7 years) diagnosed with mild to moderate dementia were included. Cognitive performance significantly improved from admission to discharge for all cognitive variables tested (p < 0.001 to 0.03). Change in global cognitive functioning, executive functions, and episodic memory were positively associated with ADL recovery. Change in global cognitive functioning predicted ADL improvements (beta= 0.32; p = 0.006). Only 7.8% of patients, characterized by worse ADL and motor abilities as well as higher frailty scores at admission, deteriorated in global cognitive scores. In comparison to patients with stable or improved cognition, these patients showed least improvements in ADL-scores (4.1 versus 12.5) and a trend for higher institutionalization (50% versus 26.5%). CONCLUSIONS: The findings highlight the potential of patients with dementia to recover cognitive functioning during rehabilitation. Cognitive change represents an independent rehabilitation outcome and a prognostic factor for successful rehabilitation suggesting that specific interventions are indicated to maintain and enhance cognitive functioning in these highly vulnerable patients. PMID- 28984598 TI - Vitamin D and the Risk of Dementia: The Rotterdam Study. AB - BACKGROUND: Vitamin D has gained interest as a potentially modifiable risk factor for dementia because of its putative neuroprotective effects. However, longitudinal studies examining the association between vitamin D and dementia have provided inconsistent results. OBJECTIVE: To determine the relationship of serum vitamin D with prevalent and incident dementia in the general population. METHODS: Within the prospective Rotterdam Study, we measured serum 25 hydroxyvitamin D concentrations between 1997 and 2001 using electrochemiluminescence-immunoassay in 6220 participants 55 years or older. We assessed dementia at baseline and continuously during follow-up until 1 January 2015. We used appropriate regression models to determine the relationship of vitamin D with prevalent and incident dementia, including Alzheimer's disease (AD). We adjusted models for age, sex, and season of blood collection. Additionally, we adjusted for ethnicity, education, cardiovascular risk factors, serum calcium, kidney function, depression, outdoor-activity and APOEE4 carriership. RESULTS: At baseline, 127 of 6,220 participants had dementia, of whom 97 had AD. Lower vitamin D concentrations were associated with a non significantly higher prevalence of dementia (adjusted OR, per SD decrease 1.20, 95% CI 0.95;1.52), but not with AD (adjusted OR: 0.97, 95% CI 0.74;1.29). Among 6,087 non-demented participants with 68,884 person-years of follow-up, 795 participants developed dementia, of whom 641 had AD. Lower vitamin D concentrations were associated with higher risk of dementia (adjusted HR, per SD decrease 1.11, 95% CI 1.02;1.20) and AD (adjusted HR: 1.13, 95% CI 1.03;1.24). CONCLUSION: Lower serum vitamin D concentrations are associated with a higher incidence of dementia. PMID- 28984599 TI - Sleep Apnea, Cognitive Profile, and Vascular Changes: An Intriguing Relationship. AB - BACKGROUND: Sleep breathing disorders can affect cognitive performances through complex brain anatomical and functional changes. OBJECTIVE: Our aim was to evaluate the correlations between cognitive performances and obstructive sleep apnea syndrome (OSAS), as well as the possible influence of vascular factors. METHODS: Thirty-four non-demented OSAS patients and 34 controls were submitted to a neuropsychological evaluation and to a vascular screening including the study of cerebrovascular reactivity by means of the breath-holding index (BHI) calculation. After 6 months, polisomnographic, neuropsychologic, and hemodynamics assessment was repeated in patients. RESULTS: At baseline, some cognitive performances involved in executive and memory functions were significantly lower in patients with respect to controls. Significantly lower values in mean BHI were also detected in patients with respect to controls (p < 0.0001). At the 6-month evaluation, 18 patients had a reduction in OSAS severity (group 1) and 16 remained stable (group 2). Group 1 patients had a significant improvement in left and mean BHI (p < 0.001) and in short-term (p = 0.02) and long-term Rey Auditory Verbal Learning Test (p < 0.001). No change in cerebrovascular reactivity and cognitive profile was detected in group 2 patients. CONCLUSIONS: Patients with OSAS may experience a reduced cognitive efficiency. Improvement of OSAS was associated to favorable hemodynamic changes and increased level of performances in verbal memory tasks so suggesting an involvement of vascular underlying mechanisms in sustaining cognitive dysfunctions in OSAS. Our preliminary data suggest the need for further studies to deepen the knowledge about the relationships between OSAS, cerebral hemodynamic compromise, and cognitive impairment risk. PMID- 28984600 TI - Plasma Amyloid-beta Levels, Cerebral Small Vessel Disease, and Cognition: The Rotterdam Study. AB - BACKGROUND: Plasma amyloid-beta (Abeta) levels are increasingly studied as a potential, accessible marker of cognitive impairment and dementia. The most common plasma Abeta isoforms, i.e., Abeta1-40 and Abeta1-42 have been linked with risk of Alzheimer's disease. However, it remains under-explored whether plasma Abeta levels including novel Abeta1-38 relate to vascular brain disease and cognition in a preclinical-phase of dementiaObjective:To examine the association of plasma Abeta levels (i.e., Abeta1-38, Abeta1-40, and Abeta1-42) with markers of cerebral small vessel disease (SVD) and cognition in a large population-based setting. METHODS: We analyzed plasma Abeta1 levels in 1201 subjects from two independent cohorts of the Rotterdam Study. Markers of SVD [lacunes, white matter hyperintensity (WMH) volume] were assessed on brain MRI (1.5T). Cognition was assessed by a detailed neuropsychological battery. In each cohort, the association of Abeta levels with SVD and cognition was performed using regression models. Estimates were then pooled across cohorts using inverse variance meta analysis with fixed effects. RESULTS: Higher levels of plasma Abeta1-38, Abeta1 40, Abeta1-42, and Abeta1-40/ Abeta1-42 ratio were associated with increasing lacunar and microbleeds counts. Moreover, higher levels of Abeta1-40 and Abeta1 40/ Abeta1-42 were significantly associated with larger WMH volumes. With regard to cognition, a higher level of Abeta1-38 Abeta1-40 and Abeta1-40/ Abeta1-42 was related to worse performance on cognitive test specifically in memory domain. CONCLUSION: Higher plasma levels of Abeta levels are associated with subclinical markers of vascular disease and poorer memory. Plasma Abeta levels thus mark the presence of vascular brain pathology. PMID- 28984601 TI - Failure to Recover from Proactive Semantic Interference and Abnormal Limbic Connectivity in Asymptomatic, Middle-Aged Offspring of Patients with Late-Onset Alzheimer's Disease. AB - BACKGROUND: We have obtained previous evidence of limbic dysfunction in middle aged, asymptomatic offspring of late-onset Alzheimer's disease (LOAD) patients, and failure to recover from proactive semantic interference has been shown to be a sensitive cognitive test in other groups at risk for LOAD. OBJECTIVE: To assess the effects of specific proactive semantic interference deficits as they relate to functional magnetic resonance imaging (fMRI) neocortical and limbic functional connectivity in middle aged offspring of individuals with LOAD (O-LOAD) and age equivalent controls. METHODS: We examined 21 O-LOAD and 20 controls without family history of neurodegenerative disorders (CS) on traditional measures of cognitive functioning and the LASSI-L, a novel semantic interference test uniquely sensitive to the failure to recover from proactive interference (frPSI). Cognitive tests then were correlated to fMRI connectivity of seeds located in entorhinal cortex and anterodorsal thalamic nuclei among O-LOAD and CS participants. RESULTS: Relative to CS, O-LOAD participants evidenced lower connectivity between entorhinal cortex and orbitofrontal, anterior cingulate, and anterior temporal cortex. In the offspring of LOAD patients, LASSI-L measures of frPSI were inversely associated with connectivity between anterodorsal thalamus and contralateral posterior cingulate. Intrusions on the task related to frPSI were inversely correlated with a widespread connectivity network involving hippocampal, insular, posterior cingulate, and dorsolateral prefrontal cortices, along with precunei and anterior thalamus in this group. Different patterns of connectivity associated with frPSI were observed among controls. CONCLUSION: The present results suggest that both semantic interference deficits and connectivity abnormalities might reflect limbic circuit dysfunction as a very early clinical signature of LOAD pathology, as previously demonstrated for other limbic phenotypes, such as sleep and circadian alterations. PMID- 28984602 TI - Modulation of Immune Responses to Herpes Simplex Virus Type 1 by IFNL3 and IRF7 Polymorphisms: A Study in Alzheimer's Disease. AB - Herpes simplex virus type 1 (HSV-1) has long been suspected to play a role in Alzheimer's disease (AD), the most common form of dementia. IFN-lambda (IFN lambda) is one of the key cytokine in innate antiviral defenses and, in particular, has an appreciable antiviral activity against HSV-1 infection. IFN lambda expression is regulated by the interaction between two different proteins: Mediator Complex 23 (MED23) and Interferon-Responsive Transcription Factor 7 (IRF7); single nucleotide polymorphisms (SNPs) in these genes as well as in IFNL3 were shown to be differently distributed in AD patients. In this study, allelic discrimination analysis for IFNL3 rs12979860, MED23 rs3756784, and IRF7 rs6598008, as well as IFN-lambda serum concentration and anti-HSV-1 antibody (Ab) titers were performed in 79 AD patients, 57 mild cognitive impairment (MCI) individuals, and 81 healthy controls (HC) who were HSV-1-seropositive. Results showed that INF-lambda serum concentration was increased in AD and MCI carrying the IFNL3 T allele compared to HC (AD versus HC: p = 0.014; MCI versus HC: p = 0.029), with the highest anti-HSV-1 Ab titers seen in AD patients carrying the IFNL3 CC genotype (p = 0.012 versus HC). Notably, anti-HSV-1 Ab titers were higher in AD and MCI individuals carrying the IRF7 AA genotype compared to HC (p = 0.018 for both). MED23 polymorphisms did not show any statistical association either with serum IFN-lambda or with anti-HSV-1 Ab. Data herein suggest that the IFNL3 rs12979860 and IRF7 rs6598008 polymorphisms modulate immune responses against HSV-1 via their effect on the IFN-lambda pathway. These results help to clarify the possible role of HSV-1 infection in AD pathogenesis. PMID- 28984603 TI - Relation of Odor Identification with Alzheimer's Disease Markers in Cerebrospinal Fluid and Cognition. AB - BACKGROUND: Impaired olfactory function is an early characteristic of Alzheimer's disease (AD), but it remains unclear if odor identification also relates to early markers of AD in cerebrospinal fluid (CSF). OBJECTIVE: To investigate the association between odor identification and amyloid-beta 1-42 (Abeta42) and total tau (t-tau) concentrations in CSF. In addition, to examine the relation between odor identification and cognitive function at baseline and at follow-up, and whether these associations are moderated by CSF Abeta42 and t-tau and apolipoprotein E (APOE) genotype. METHODS: We included 160 individuals (40 with normal cognition, 45 with mild cognitive impairment (MCI), 42 with AD-type dementia, and 26 individuals with non-AD dementia) from the EDAR study. Individuals were recruited from six memory clinics across Europe. Odor identification was tested with the brief University of Pennsylvania Smell Identification Test. CSF Abeta42 and t-tau were assessed with INNO-BIA AlzBio3 Luminex assay. Neuropsychological assessment included tests for verbal memory, verbal fluency, attention, executive function, and visuoconstruction. Follow-up was performed within 3 years after baseline. RESULTS: Lower odor identification scores correlated with increased CSF t-tau concentrations and with lower scores on all cognitive measures at baseline independent of diagnostic group. Lower odor identification scores predicted decline on the MMSE in the total group, and decline on wordlist learning and delayed recall in APOE E4 carriers and in individuals with abnormal Abeta42. CONCLUSION: Odor identification impairment may be an indicator of neuronal injury rather than amyloid pathology. PMID- 28984605 TI - The Pitfall of Behavioral Variant Frontotemporal Dementia Mimics Despite Multidisciplinary Application of the FTDC Criteria. AB - BACKGROUND: The behavioral variant of frontotemporal dementia (bvFTD) has a broad differential diagnosis including other neurological and psychiatric disorders. Psychiatric misdiagnoses occur in up to 50% of bvFTD patients. Numbers on misdiagnosis of bvFTD in psychiatric disorders are lacking. OBJECTIVE: The aim of our study was to investigate the frequency and characteristics of bvFTD misdiagnoses in psychiatric disorders and other neurologic disorders. METHODS: Thirty-five patients with a (possible or probable) bvFTD diagnosis made by specialized memory clinic neurologists were included. Change in diagnosis after consulting a psychiatrist at baseline was recorded as well as change in diagnosis after two years of multidisciplinary neuropsychiatric follow-up. Differences in cognitive and behavioral profiles were investigated per diagnostic group after follow-up (bvFTD, psychiatry, other neurologic disorders). Clinical profiles are described in detail. RESULTS: In 17 patients (48.5%), the bvFTD baseline diagnosis changed: Two at baseline after psychiatric consultation, and 15 after two years of multidisciplinary follow-up. Eleven (64.5%) of these 17 patients (31.5% of total) were reclassified with a psychiatric diagnosis. We found no differences for cognitive baseline profiles between patients with bvFTD versus psychiatric diagnoses. CONCLUSION: In almost half of cases, the initial bvFTD diagnosis was changed after follow-up, most often into a psychiatric disorder. A multidisciplinary neuropsychiatric approach in the diagnostic process of bvFTD results in the identification of treatable disorders. Our findings illustrate a limited specificity of the [18F]FDG-PET-scan and the bvFTD criteria in a neuropsychiatric cohort, especially combined with certain clinical symptoms, like disinhibition, apathy, or loss of empathy. PMID- 28984604 TI - Alzheimer's Disease-Related Polymorphisms in Shunt-Responsive Idiopathic Normal Pressure Hydrocephalus. AB - BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is a late onset, surgically treated progressive brain disease caused by impaired cerebrospinal fluid dynamics and subsequent ventriculomegaly. Comorbid Alzheimer's disease (AD) seems to be frequent in iNPH. OBJECTIVE: We aim to evaluate the role of AD related polymorphisms in iNPH. METHODS: Overall 188 shunt-operated iNPH patients and 688 controls without diagnosed neurodegenerative disease were included into analysis. Twenty-three single-nucleotide polymorphisms (SNPs FRMD4A [rs7081208_A, rs2446581_A, rs17314229_T], CR1, BIN, CD2AP, CLU, MS4A6A, MS4A4E, PICALM, ABCA7, CD33, INPP5D, HLA_DRB5, EPHA1, PTK2B, CELF1, SORL1, FERMT2, SLC24A, DSG2, CASS4, and NME8) adjusted to APOE were analyzed between groups by using binary logistic regression analysis. Neuroradiological characteristics and AD-related changes in the right frontal cortical brain biopsies were available for further analysis. RESULTS: Logistic regression analysis adjusted to age, gender, and other SNPs indicated allelic variation of NME8 between iNPH patients and non-demented controls (p = 0.014). The allelic variation of NME8 was not related to the neuropathological changes in the brain biopsies of iNPH patients. However, periventricular white matter changes (p = 0.017) were more frequent in the iNPH patients with the AA-genotype, an identified risk factor of AD. CONCLUSIONS: Our findings increase the evidence that iNPH is characterized by genetic and pathophysiological mechanisms independent from AD. Considering that NME8 plays a role in the ciliary function and displays SNP-related diversity in white matter changes, the mechanisms of NME8 in iNPH and other neurodegenerative processes are worth further study. PMID- 28984606 TI - The Use of Music Playlists for People with Dementia: A Critical Synthesis. AB - The use of pre-recorded music to ease behavioral and psychological symptoms associated with dementia is popular in health-care contexts in both formal music therapy settings and in non-therapist led interventions. However, further understanding of how non-therapist led interventions compare to therapist led interventions is needed. This paper reviews 28 studies that used pre-recorded music with people with dementia using a critical interpretive synthesis model. Results revealed that pre-recorded music can be effective in reducing a variety of affective and behavioral symptoms, in particular agitation, even where a trained music therapist is not present. However, the results are not universally positive, suggesting the need for further clarification of protocols for music use and closer investigation of variables that influence individual responseto music. PMID- 28984607 TI - Co-Localization of Glia Maturation Factor with NLRP3 Inflammasome and Autophagosome Markers in Human Alzheimer's Disease Brain. AB - Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by the presence of intracellular neurofibrillary tangles (NFTs) containing hyperphosphorylated tau, and the extracellular deposition of amyloid plaques (APs) with misfolded amyloid-beta (Abeta) peptide. Glia maturation factor (GMF), a highly conserved pro-inflammatory protein, isolated and cloned in our laboratory, has been shown to activate glial cells leading to neuroinflammation and neurodegeneration in AD. We hypothesized that inflammatory reactions promoted by NLRP3-Caspase-1inflammasome pathway trigger dysfunction in autophagy and accumulation of Abeta which is amplified and regulated by GMF in AD. In this study, using immunohistochemical techniques we analyzed components of the NLRP3 inflammasome and autophagy- lysosomal markers in relation to Abeta, p-tau and GMF in human postmortem AD and age-matched non-AD brains. Tissue sections were prepared from the temporal cortex of human postmortem brains. Here, we demonstrate an increased expression of the inflammasome components NLRP3 and Caspase-1 and the products of inflammasome activation IL-1beta and IL-18 along with GMF in the temporal cortex of AD brains. These inflammasome components and the pro-inflammatory cytokines co-localized with GMF in the vicinity and periphery of the APs and NFTs. Moreover, using double immunofluorescence staining, AD brain displayed an increase in the autophagy SQSTM1/p62 and LC3 positive vesicles and the lysosomal marker LAMP1 that also co-localized with GMF, Abeta and hyperphosphorylated p-tau. Our results indicate that in AD, the neuroinflammation promoted by the NLRP3 inflammasome may be amplified and regulated by GMF, which further impairs clearance of protein aggregates mediated by the auto-phagosomal pathway. PMID- 28984608 TI - Damage to the Frontal Aslant Tract Accounts for Visuo-Constructive Deficits in Alzheimer's Disease. AB - The frontal aslant tract (FAT) has been described as a bundle connecting the Broca's area to the supplementary motor area (SMA) and the pre-SMA in both hemispheres. The functional properties of this tract and its role in degenerative dementia, such as Alzheimer's disease (AD), still need to be fully clarified. The aim of this study was to explore the microstructural integrity of the FAT in patients with AD and its potential relationship with cognitive functioning. Twenty-three patients with AD and 25 healthy subjects (HS) were enrolled. All subjects underwent cognitive and MRI examination. MRI, including diffusion sequences, was used for probabilistic tractography analysis. We reconstructed individual FATs bilaterally and assessed their microstructural integrity using fractional anisotropy (FA), computed as both mean tract value and voxel-wise using SPM-8. Mean FA values were then used to test for correlations with cognitive measures. Mean tract FA and voxel-wise analyses revealed that patients with AD, compared to HS, had decreased FA in the FAT bilaterally. In addition, positive associations were found between FA in the FATs and patients' performance at tests for constructional praxis and visuospatial logical reasoning. The present results reveal a bilateral damage of FAT in AD patients. The association between FATs' microscopic abnormalities and constructive abilities fits well with the knowledge of a functional involvement of SMA and pre-SMA in movement sequences when executing constructive praxis tasks. The FAT is an associative bundle critically involved in the network sub-serving constructional praxis in patients with AD. PMID- 28984613 TI - The Impact of Family History on the Clinical Features of Huntington's Disease. AB - BACKGROUND: Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder. In most cases the disease is inherited from a parent, although a considerable number of affected persons have no reported family history of the disease. While CAG repeat length is negatively correlated with age of symptom onset, variability exists suggesting that other variables may influence symptom onset. OBJECTIVES: The objective of this study is to determine whether awareness of a family history of HD has an impact on symptom onset and disease manifestations. METHODS: Data were obtained from Enroll-HD to compare subjects with a family history of HD to subjects without on various key clinical outcomes. In addition, multiple regressions were performed to investigate the impact of family history on the age at onset of depression and motor symptoms. RESULTS: 4,285 mutation positive subjects were included in the analysis, of which 4.81% had a negative family history. Controlling for CAG repeat length, a positive family history predicted an onset of depression 11.438 years earlier and an onset of motor symptoms 6.681 years earlier when compared to having a negative family history. Subjects with a positive family history were more likely to report behavioral manifestations as the initial major symptom of HD (38.6% vs. 29.6%, p = 0.023), and were more likely to report previous suicidal ideation/attempts (26.2% vs. 20.3%, p = 0.046). CONCLUSIONS: A positive family history of HD appears to be associated with an earlier onset of depression and overall disease manifestations. Implications regarding the role of genetic versus environmental contributions to symptom onset in HD are discussed. PMID- 28984614 TI - Progression of Duchenne Cardiomyopathy Presenting with Chest Pain and Troponin Elevation. AB - BACKGROUND: Improved neuromuscular and respiratory therapies have altered the natural history of Duchenne muscular dystrophy (DMD) such that the most common cause of mortality is progressive cardiomyopathy. Despite imaging evidence of progressive cardiomyopathy, troponin I (cTn) is not significantly elevated in asymptomatic DMD patients. RESULTS: We describe eight boys with DMD evaluated for acute chest pain (ACP) and found to have acute cTn elevation with depressed left ventricular ejection fraction (LVEF). Of our eight patients, five presented with a primary complaint of ACP, while three presented with secondary myocardial injury in the context of systemic illness requiring hospitalization. Electrocardiograms showed diffuse ST changes and mean peak cTn level was 44+/ 15.4 ng/mL (reference range <0.03 ng/mL). cTn levels normalized with only supportive care. Cardiac magnetic resonance imaging (CMR) was performed during the event on all but one patient, demonstrating increased late gadolinium enhancement (LGE) from 12.4+/-11.4% to 36.5+/-10.3% with associated deterioration of LVEF from 61+/-4.4% to 47.6+/-6.6% which remained depressed on follow-up CMR study (49.1+/-7.8%). All viral studies were negative. Additional investigations varied among patients, but no causative findings were demonstrated. CONCLUSIONS: ACP with cTn elevation occurs in DMD boys and may be indicative of cardiomyopathy progression as evidenced by acute left ventricular dysfunction and development or progression of myocardial fibrosis. This clinical presentation is under recognized. These events may represent an important pathophysiological mechanism in cardiomyopathy progression. PMID- 28984615 TI - Initiation of Levodopa-Carbidopa Intestinal Gel Infusion Using Telemedicine (Video Communication System) Facilitates Efficient and Well-Accepted Home Titration in Patients with Advanced Parkinson's Disease. AB - BACKGROUND: Levodopa-carbidopa intestinal gel (LCIG; Duodopa(r)) is used for continuous infusion in advanced Parkinson's disease. To achieve optimal effect, the LCIG dose is individually titrated, traditionally conducted during hospitalization in Sweden. However, dose adjustment depends on surrounding conditions, physical activity, and emotional stress, which is why titration at home could be beneficial. Telemedicine (TM) using a video communication system offers alternative titration procedures, allowing LCIG initiation at home. OBJECTIVE: Study objectives were to show the feasibility of TM for LCIG home titration, evaluate resource use, and assess patient, neurologist, and nurse satisfaction. METHODS: Four clinics enrolled 15 patients to observe efficiency and feasibility of TM-based monitoring. RESULTS: Patient median (range) age was 67 (52-73) years and time since diagnosis was 10 (7-23) years. Median time between LCIG initiation and end of TM-assisted titration was 2.8 (2.0-13.8) days. Median time required for home titration by neurologists, nurses, and patients was (hours:minutes) 1 : 14 (0 : 29-1 : 52), 5 : 49 (2 : 46-10 : 3), and 8 : 53 (4 : 11-14 : 11), respectively. Neurologists and nurses considered this to be less time than required for hospital titration. TM allowed patients 92% free time from start to end of titration. Technical problems associated with TM contacts were rare, mostly related to digital link, and quickly resolved. Patients, neurologists, and nurses were satisfied using TM. No serious adverse events were reported; there was one device complaint (tube occlusion). CONCLUSIONS: In this study, TM-assisted LCIG titration at home was resource-efficient, technically feasible, well-accepted and was deemed satisfactory by patients, neurologists, and nurses. PMID- 28984616 TI - The Role of Vitamin D in Disease Progression in Early Parkinson's Disease. AB - BACKGROUND: Previous cross-sectional studies have shown that Parkinson's disease (PD) patients have lower serum 25-hydroxy vitamin D (25(OH)D) concentrations than controls. Vitamin D deficiency was associated with increased disease severity and cognitive impairment in prevalent PD patients. OBJECTIVE: The aim of the study was to determine 25(OH)D in newly diagnosed PD and age-matched controls and to assess if there was an association with clinical outcomes (disease severity, cognition and falls) over the 36-month follow up period. METHODS: A prospective observational study of newly diagnosed PD patients in the North East of England with age-matched controls (PD, n = 145; control, n = 94). Serum 25(OH)D was assessed at baseline and 18 months. Participants underwent clinical assessment at baseline, 18 and 36 months. One hundred and ten participants with PD also took part in a prospective falls study. RESULTS: Mean serum 25(OH)D concentrations were lower in PD than control participants at baseline (44.1+/-21.7 vs. 52.2+/ 22.1 nmol/L, p < 0.05) and 18 months (44.2+/-23.6 vs. 55.7+/-28.8 nmol/L, p < 0.05). Baseline serum 25(OH)D concentration, age, motor score and dosage of dopaminergic medication were significant predictors of variance of motor severity at 36 months ((DeltaR2 = 0.039, F = 6.6, p < 0.01). Serum 25(OH)D was not associated with cognition or falls during the follow up period. CONCLUSIONS: Patients with incident PD had significantly lower serum 25(OH)D concentrations than age-matched controls, which may have implications in terms of bone health and fracture risk. There was a small but significant association between vitamin D status at baseline and disease motor severity at 36 months. PMID- 28984617 TI - Differences in Parkinson's Disease Risk with Caffeine Intake and Postmenopausal Hormone Use. AB - BACKGROUND: Caffeine intake has been associated with a lower risk of Parkinson's disease (PD). This association is robust in men, but inconsistent in women due to a possible interaction with post-menopausal hormone (PMH) use. OBJECTIVE: To (1) evaluate the association between caffeine intake and PD risk and (2) assess potential effect modification of the association by PMH use among women. METHODS: We examined associations between caffeine intake and incident PD risk in the Nurses' Health Study (NHS) (N = 121,701 women) and the Health Professionals Follow-up Study (HPFS) (N = 51,529 men). Dietary data on coffee and caffeine from other sources were collected every four years using a validated semi-quantitative food frequency questionnaire for both cohorts. Information on lifestyle and incident PD diagnosis was updated biennially and PD diagnoses were confirmed by medical record review. We estimated hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional hazards models. RESULTS: We documented a total of 1,219 PD cases over the follow-up period. The multivariable-adjusted HR comparing the highest to lowest quintile of caffeine intake was 0.50 (95% CI: 0.37, 0.68; Ptrend<0.0001) in the HPFS. Among women, there was a suggestion of an interaction between coffee intake and PMH use (P = 0.08). In the pooled analyses combining men and women who have never used PMH, the risk of PD was lower as coffee intake increased (Ptrend<0.001). CONCLUSIONS: Our results support previous findings that increased caffeine intake may be associated with a decreased PD risk in men and women who have never used PMH. PMID- 28984618 TI - Reduced TH expression and alpha-synuclein accumulation contribute towards nigrostriatal dysfunction in experimental hepatic encephalopathy. AB - PURPOSE: The present work examines alpha-synuclein expression in the nigrostriatal system of a rat chronic hepatic encephalopathy model induced by portacaval anastomosis (PCA). There is evidence that dopaminergic dysfunction in disease conditions is strongly associated with such expression. Possible relationships among dopaminergic neurons, astroglial cells and alpha-synuclein expression were sought. METHODS: Brain tissue samples from rats at 1 and 6 months post-PCA, and controls, were analysed immunohistochemically using antibodies against tyrosine hydroxylase (TH), alpha-synuclein, glial fibrillary acidic protein (GFAP) and ubiquitin (Ub). RESULTS: In the control rats, TH immunoreactivity was detected in the neuronal cell bodies and processes in the substantia nigra pars compacta (SNc). A dense TH-positive network of neurons was also seen in the striatum. In the PCA-exposed rats, however, a reduction in TH positive neurons was seen at both 1 and 6 months in the SNc, as well as a reduction in TH-positive fibres in the striatum. This was coincident with the appearance of alpha-synuclein-immunoreactive neurons in the SNc; some of the TH positive neurons also showed alpha-synuclein immunoreactivity. In addition, alpha synuclein accumulation was seen in the SNc and striatum at both 1 and 6 months post-PCA, whereas alpha-synuclein was only mildly expressed in the nigrostriatal pathway of the controls. Astrogliosis was also seen following PCA, as revealed by increased GFAP expression from 1 month to 6 months post-PCA in both the SN and striatum. The astroglial activation level in the SN paralleled the reduced neuronal expression of TH throughout PCA exposure. CONCLUSION: alpha-synuclein accumulation following PCA may induce dopaminergic dysfunction via the downregulation of TH, as well as astroglial activation. PMID- 28984619 TI - The therapeutic use of non-invasive brain stimulation in multiple sclerosis - a review. AB - BACKGROUND: Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system and a leading cause of disability in young adults. Many disabling symptoms in MS, such as spasticity, pain, depression and cognitive deficits are not fully controlled by drug treatment. Non-invasive brain stimulation (NIBS) techniques can be used as tools for modulating altered cortical excitability and plasticity MS patients, providing an improvement in disabling symptoms affecting such patients. OBJECTIVE: This review reported and summarized some of the most interesting and promising recent achievements regarding the therapeutic use of NIBS in MS patients. METHODS: We reviewed the clinical application of transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS), emphasizing their effect on clinical symptoms and signs that are commonly involved in MS patients. In addition, we shortly described new NIBS protocols, such as transcranial alternating current stimulation and transcranial focused ultrasound stimulation as potential and innovative therapeutic options to be applied in future studies in MS patients. RESULTS: We reviewed twenty-one studies covering six main clinical domains. Most of such studies focused on fatigues (33.3%), motor performance (19%) and spasticity (19%), sparse results were about pain (9.5%), cognitive abilities (9.5%), sensory deficit (4.8%) and bladder function (4.8%). The most promising results have been published for the improvement of motor (i.e. hand dexterity) and cognitive performances (i.e. attention and working memory) by applying rTMS or tDCS alone or in association with motor/cognitive training, for pain's treatment by using tDCS. CONCLUSION: There are still no official recommendations for the therapeutic use of tDCS or rTMS in MS. The huge inter individual variability of NIBS efficacy is still a big challenge which needs to be solved. However, well-designed studies, deeper knowledge about pathomechanisms underlying MS, and the combination of such techniques with motor and cognitive rehabilitation might results in higher effectiveness of NIBS. PMID- 28984620 TI - Making if-then plans counteracts learned non-use in stroke patients: A proof-of principle study. AB - BACKGROUND: After stroke, the learned non-use of a paretic arm is a major obstacle to the improvement of hand function. OBJECTIVE: We examined whether patients with a central paresis could profit from applying the self-regulation strategy of making if-then plans that specify situational triggers to using the paretic arm. METHOD: Seventeen stroke patients with a mild to moderate hand paresis were asked to perform a Simon task which is commonly used to study the enhanced executive control needed when there is a mismatch between stimulus (e.g., color) and response (e.g., location) features. We examined whether patients with hemiparesis would be able to reduce the Simon effect (i.e., responding slower to mismatched as compared to matched stimulus and response features) by creating new stimulus-response associations via if-then plans. RESULTS: A significant Simon effect was observed in both the affected and the non affected arm for control trials. However, there was no longer a significant Simon effect for the critical trials prepared by forming if-then plans. This led to a significant stimulus*compatibility interaction effect for the affected arm and a marginally significant interaction effect for the non-affected arm. Making if then plans was effective for eliminating or at least reducing the Simon effect for the affected and the non-affected arm, respectively. CONCLUSION: This observation opens a potential new route to improving stroke rehabilitation. If then plans may qualify as a viable strategy to overcome the learned non-use of the affected arm. Further research is now required to develop and test therapeutic measures based on this proof-of-principle. PMID- 28984622 TI - Follicular psoriasis - dermoscopic features at a glance. PMID- 28984621 TI - The effects of exercise on cognitive function and brain plasticity - a feasibility trial. AB - BACKGROUND: Exercise-mediated cognitive improvements can be at least partly attributed to neuroplastic changes in the nervous system, and may be influenced by the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene. Transcranial magnetic stimulation (TMS) can be used to assess mechanisms of plasticity in humans noninvasively. OBJECTIVES: To assess the feasibility of evaluating the effects of short-term regular exercise on cognitive performance, and to evaluate the relationship between these effects, TMS measures of plasticity, and BDNF Met carrier status in young healthy sedentary adults. METHODS: Of the 19 participants who enrolled in the study, 14 sedentary adults (12 females, age mean+/-SD, 27+/-12.3 yr), with less than two sessions of physical exercise in the preceding 2 months, completed an aerobic exercise regimen including four 30-min daily sessions per week for 4 weeks (for a total of 16 sessions) delivered at 55-64% of age-predicted maximal heart rate. Prior to and following the exercise regimen, participants performed a neuropsychological test battery and an intermittent theta-burst TMS plasticity protocol. RESULTS: All participants completed the various measures and adhered to the exercise regimen. There were no complications and the results obtained were reliable. The feasibility of the approach is thus well established. Between-group comparisons of pre-post change revealed trends toward increased performance on the Stroop and faster reaction times in the CPT detectability in the Val66Val subgroup (p = 0.07 and p = 0.08), and a reduction in TBS-induced modulation of TMS responses in Met carriers (p = 0.07). CONCLUSION: Acute exercise interventions in sedentary adults can be meaningfully conducted along with cognitive and neurophysiologic measures to assess behavioral and neurobiological effects and assessment of BDNF polymorphism. TMS measures of plasticity can be used to evaluate the effects of exercise on brain plasticity, and relate them to neuropsychological measures of cognition. PMID- 28984623 TI - Intradermal spindle cell/pleomorphic lipoma: Case report and review of the literature. PMID- 28984624 TI - Facial multiple xanthogranuloma in an adult. PMID- 28984625 TI - Low-dose methotrexate combined with superficial X-ray in the treatment of folliculotropic mycosis fungoides: A case report. PMID- 28984626 TI - Treatment of drug-induced hypersensitivity syndrome with cyclosporine. PMID- 28984627 TI - Extranodal natural killer/T cell lymphoma, nasal type presenting as recurrent facial cellulitis. PMID- 28984628 TI - Encouraging curricular research: A new agenda for IJDVL. PMID- 28984629 TI - Extranodal natural killer T-cell lymphoma mimicking cellulitis and venous thrombosis: A case report. PMID- 28984630 TI - Perioperative Management of the Adult Patient on Venovenous Extracorporeal Membrane Oxygenation Requiring Noncardiac Surgery. AB - The use of venovenous extracorporeal membrane oxygenation is increasing worldwide. These patients often require noncardiac surgery. In the perioperative period, preoperative assessment, patient transport, choice of anesthetic type, drug dosing, patient monitoring, and intraoperative and postoperative management of common patient problems will be impacted. Furthermore, common monitoring techniques will have unique limitations. Importantly, patients on venovenous extracorporeal membrane oxygenation remain subject to hypoxemia, hypercarbia, and acidemia in the perioperative setting despite extracorporeal support. Treatments of these conditions often require both manipulation of extracorporeal membrane oxygenation settings and physiologic interventions. Perioperative management of anticoagulation, as well as thresholds to transfuse blood products, remain highly controversial and must take into account the specific procedure, extracorporeal membrane oxygenation circuit function, and patient comorbidities. We will review the physiologic management of the patient requiring surgery while on venovenous extracorporeal membrane oxygenation. PMID- 28984631 TI - Right Ventricular Perfusion: Physiology and Clinical Implications. AB - Regulation of blood flow to the right ventricle differs significantly from that to the left ventricle. The right ventricle develops a lower systolic pressure than the left ventricle, resulting in reduced extravascular compressive forces and myocardial oxygen demand. Right ventricular perfusion has eight major characteristics that distinguish it from left ventricular perfusion: (1) appreciable perfusion throughout the entire cardiac cycle; (2) reduced myocardial oxygen uptake, blood flow, and oxygen extraction; (3) an oxygen extraction reserve that can be recruited to at least partially offset a reduction in coronary blood flow; (4) less effective pressure-flow autoregulation; (5) the ability to downregulate its metabolic demand during coronary hypoperfusion and thereby maintain contractile function and energy stores; (6) a transmurally uniform reduction in myocardial perfusion in the presence of a hemodynamically significant epicardial coronary stenosis; (7) extensive collateral connections from the left coronary circulation; and (8) possible retrograde perfusion from the right ventricular cavity through the Thebesian veins. These differences promote the maintenance of right ventricular oxygen supply-demand balance and provide relative resistance to ischemia-induced contractile dysfunction and infarction, but they may be compromised during acute or chronic increases in right ventricle afterload resulting from pulmonary arterial hypertension. Contractile function of the thin-walled right ventricle is exquisitely sensitive to afterload. Acute increases in pulmonary arterial pressure reduce right ventricular stroke volume and, if sufficiently large and prolonged, result in right ventricular failure. Right ventricular ischemia plays a prominent role in these effects. The risk of right ventricular ischemia is also heightened during chronic elevations in right ventricular afterload because microvascular growth fails to match myocyte hypertrophy and because microvascular dysfunction is present. The right coronary circulation is more sensitive than the left to alpha adrenergic-mediated constriction, which may contribute to its greater propensity for coronary vasospasm. This characteristic of the right coronary circulation may increase its vulnerability to coronary vasoconstriction and impaired right ventricular perfusion during administration of alpha-adrenergic receptor agonists. PMID- 28984632 TI - Effect of High-Dose Allopurinol Pretreatment on Cardiac Biomarkers of Patients Undergoing Elective Percutaneous Coronary Intervention: A Randomized Clinical Trial. AB - BACKGROUND: Increased accumulation of reactive oxygen species contributes to pathophysiologic states such as endothelial dysfunction, metabolic and functional impairment, inflammatory activation, and other features of cardiovascular pathophysiology. Allopurinol acts as a xanthine oxidase inhibitor that reduces the amount of free radicals after reactive oxygen species generation. METHODS AND RESULTS: In this placebo-controlled randomized clinical trial, all patients admitted with coronary artery disease who are candidates for elective percutaneous coronary intervention (PCI) were included. The 254 patients were randomly divided into 2 groups. Blood samples for cardiac biomarkers (creatine kinase [CK]-MB and troponin T [cTnT]) were collected from all patients after admission (the day before PCI), and also 8 and 16 hours after intervention. In group 1 (133 patients), 600 mg allopurinol was orally administered on the day before PCI, and another same dose on the day of PCI, and the elective PCI was performed. In group 2 (121 patients), elective PCI was performed without pretreatment with allopurinol. In an unadjusted model, the serum levels of both CK-MB and cTnT, 16 hours after PCI were higher in the placebo group as compared with the allopurinol group, although it was statistically insignificant. We compared the maximum levels of CK-MB and cTnT (8 or 16 hours after PCI) and their maximum changes in both groups. After adjustment for confounders, use of allopurinol did not have any statistically significant association with the rise of cardiac-spec-fic enzymes. CONCLUSIONS: Allopurinol could not be effective significantly, in patients undergoing elective PCI, to decrease cardiac-specific enzymes, and seems not to be of use before PCI. PMID- 28984633 TI - Homeopathy as Boundary Object and Distributed Therapeutic Agency. A Discussion on the Homeopathic Placebo Response. AB - BACKGROUND: We discuss homeopathy's placebo effect as the result of a distributed therapeutic agency involving humans, objects, and texts. Homeopathy has been involved in controversies for centuries, and the dispute whether it is therapy or quackery is as lively as ever. Still, homeopathy has retained significant popularity and acceptance within the medical establishment. AREAS OF UNCERTAINTY: We bracket the issue of biochemical effectiveness of homeopathic remedies as we only discuss homeopathy's potential to elicit a placebo response within its therapeutic alliance, in virtue of its social, symbolic, and material features. DATA SOURCES: The review is based on literature discussing homeopathic effectiveness, including historical, biographical, sociological, and epistemological perspectives. We build upon research that clarifies the therapeutic relationship, examining its activities and meanings for practitioners and patients. RESULTS: Previous analyses discussing homeopathy's placebo effect stress the importance of the individualized consultation that functions as psychotherapy and generates empathy and hope. We enlarge the discussion, highlighting homeopathy's distributed therapeutic agency across humans, texts, and materials. The historical evolution of homeopathy in relation to biomedicine and science is important to understand its institutional integration into mainstream medicine and its appeal to scientifically minded doctors. Anecdotes of healing and the message of no-harm encourage patients to try homeopathy and hope for the best. The esthetics and ritual of remedies, coupled with computers' scientific legitimacy and time-saving power constitute a material infrastructure of therapeutic persuasion. CONCLUSIONS: Through its relation with biomedicine, its doctrine, consultation design, and treatment rituals, homeopathy offers a powerful medium to elicit a placebo response in a therapeutic alliance. By virtue of its proximity and radical difference from the scientific and biomedical enterprises, its material and textual organization, its storytelling and esthetics, homeopathy offers doctors and patients the opportunity and the tools to collaborate, to witness healing, and to hope for success against adversity. PMID- 28984634 TI - Using eHealth to Increase Autonomy Supportive Care: A Multicenter Intervention Study in Antenatal Care. AB - eHealth solutions are increasingly implemented in antenatal care to enhance women's involvement. The main aim of this study was to evaluate women's assessment of autonomy supportive care during the antenatal care visits among low risk pregnant women. An intervention study was conducted including a control group attending standard antenatal care and an intervention group having access to an eHealth knowledge base, in addition to standard care. A total of 87 women were included in the control group and a total of 121 women in the intervention group. Data were collected using an online questionnaire 2 weeks after participants had given birth. Data were analyzed using chi tests and Wilcoxon rank sums. Use of an eHealth knowledge base was associated with statistically significant higher scores for women's overall assessment of antenatal care visits, the organization of antenatal care visits, confidence after antenatal care visits, and involvement during antenatal care visits. We also found a statistically significant higher overall self-perceived autonomy supportive care in the intervention group compared with the control group. PMID- 28984635 TI - The association between self-reported versus nicotine metabolite-confirmed smoking status and coronary artery calcification. AB - OBJECTIVE: There are no data comparing the relationship between coronary artery calcification and self-reported and cotinine-verified smoking. This study was carried out to evaluate the relationship between coronary artery calcium (CAC) and urinary cotinine or self-reported smoking status in Korean adults. PARTICIPANTS AND METHODS: Study participants included 22 797 individuals (19 181 men; mean age+/-SD 39.2+/-7.1 years) who were enrolled in the Kangbuk Samsung Health Study and Kangbuk Samsung Cohort Study between 2011 and 2013, and who had urinary cotinine and CAC measurements. Cotinine-verified current smokers were defined as having a urinary cotinine level of above 50 ng/ml. RESULTS: The prevalence of never smokers, former smokers, and current smokers according to the self-reported questionnaires was 44.6, 24.2, and 31.2%, respectively, and that of cotinine-verified current smokers was 30.2%. The prevalence of the presence of CAC in self-reported current smokers was higher than that in self-reported never/former smokers (13.7 vs. 10.2%, P<0.001), and that in cotinine-verified current smokers was higher than that in cotinine-verified never smokers (14.0 vs. 10.2%, P<0.001). A multivariate logistic regression model adjusted for the variables with univariate relationships showed that self-reported former smokers and current smokers had significantly increased odds ratio (OR) for the presence of CAC compared with self-reported never smokers [OR (95% confidence interval): 1.20 (1.03-1.40) in former smokers and 1.29 (1.11-1.50) in current smokers]. Cotinine-verified current smokers also showed a significant association with the presence of CAC [1.23 (1.12-1.35)]. Furthermore, log-transformed cotinine levels increased the OR for the presence of CAC [1.03 (1.01-1.05)]. CONCLUSION: This study is the first large cohort study to show that both self-reported and cotinine-verified smoking is associated independently with the presence of CAC in Korean adults. PMID- 28984637 TI - What do we tell patients with coronary artery disease about marijuana use? PMID- 28984636 TI - Coronary artery-positive remodeling in current smokers. AB - BACKGROUND: This study aims to evaluate the association of the coronary artery positive remodeling (CAPR) observed on cardiac computed tomography angiography (CCTA) with cigarette smoking. PATIENTS AND METHODS: This retrospective case control study enrolled 178 consecutive patients with CAPR plaque (case group) and 180 consecutive patients with coronary artery plaque, but no positive remodeling (control group). CAPR was evaluated in CCTA images and defined as at least 10% larger vessel diameter at the plaque site compared with a normal reference segment. RESULTS: The average age of this population was 61.8+/-11.5 years (30.4% women). In the case group, the prevalences of current smokers, former smokers, and nonsmokers were 15.7, 26.4, and 57.9%, respectively. In the control group, the prevalences were 6.1, 20.6, and 73.3%, respectively, which were significantly different from the control group (P=0.002 for all). In a subanalysis of the CAPR location in the CAPR group, CAPR was more prevalent in the proximal than the distal segments of the major coronary arteries. Most of the patients in the case group had only one segment involvement with CAPR (71.35%). Logistic regression analyses showed that a history of current smoking has a significant correlation with CAPR in both unadjusted and adjusted models after controlling for risk factors. Current smokers have a 3.5-fold higher risk of having CAPR compared with nonsmokers (P<0.01). CONCLUSION: There is a significant independent association between a history of cigarette smoking and CAPR evaluated by CCTA. Current cigarette smokers have a 3.5 times higher risk of having CAPR. PMID- 28984638 TI - The future of nonoperating room anesthesia in the 21st century: emphasis on quality and safety. AB - PURPOSE OF REVIEW: Nonoperating room anesthesia (NORA) has grown from an insignificant percentage of total anesthesia cases into a major percentage of anesthesia workload over the past 30 years. This trend evidences no signs of abating. RECENT FINDINGS: With the rapid development of novel interventional techniques in cardiology, radiology, gastroenterology and pulmonary medicine and other areas, the core responsibilities of the anesthesia provider will no longer be confined to delivering care in traditional operating rooms. This change presents challenges for the profession on several fronts. Efficient staffing of multiple locations poses challenges. The demand for anesthesia services continues to increase, but underutilization is a major problem. Each clinical area presents unique patient care issues. New interventional techniques are continually developed with which anesthesiologists need to be familiar in each specific area. NORA patients are older and medically complex, yet many are treated on an outpatient basis. Consequently, anesthetic management for NORA will of necessity require techniques that allow patients to recover quickly. SUMMARY: It may be anticipated that in the next decade that NORA cases will constitute over 50% of the number of cases performed with anesthesia involvement. As the last century belonged to invasive surgery, the next century will belong to interventionalists. There is also an increasing national emphasis on quality measurement and metrics reporting. Future anesthesia payment models under Medicare Access and CHIP Reauthorization Act, such as merit-based incentive payment system (MIPS), emphasize various process and outcomes measures. Anesthesiologists will be evaluated based on a composite performance score consisting of four components: quality, resource use, clinical practice improvement activities and meaningful use of certified electronic health record technology. PMID- 28984640 TI - Predictors of Driving Cessation in Dementia: Baseline Characteristics and Trajectories of Disease Progression. AB - A diagnosis of dementia implies the eventual need to relinquish driving. This is associated with significant morbidity and anticipating when it will need to occur can be important for planning. Patients, however, vary in the course of their disease. We sought to identify predictors of driving cessation in patients with dementia, including both baseline characteristics and changes in cognition and function over time as indicators of disease trajectory. A total of 779 patients with dementia were recruited from 9 memory clinics around Australia. Patients and their carers reported their driving status and completed measures of dementia severity, cognition, function, neuropsychiatric symptoms, and medication use at regular intervals over a 3-year period. Of the 247 patients still driving at baseline, 147 (59.5%) stopped driving during the study. Variables that predicted driving cessation included older age; female sex; greater dementia severity and cognitive and functional impairments at baseline; and greater increases in dementia severity and cognitive and functional impairments over 3 and 6 month periods. The findings confirm that easily assessable characteristics, including changes over time, predict future driving status. The findings underscore the value of regularly assessing patients with standardized measures to determine disease trajectory and likely prognosis. PMID- 28984639 TI - Baseline White Matter Hyperintensities and Hippocampal Volume are Associated With Conversion From Normal Cognition to Mild Cognitive Impairment in the Framingham Offspring Study. AB - INTRODUCTION: We examined associations between magnetic resonance imaging (MRI) markers of cerebrovascular disease and neurodegeneration with mild cognitive impairment (MCI) diagnosis at baseline and conversion from normal cognition to MCI at follow-up. METHODS: Framingham Offspring participants underwent brain MRI and neuropsychological assessment at baseline (n=1049) and follow-up (n=561). Participants were classified at baseline and at follow-up as cognitively normal or MCI using sensitive neuropsychological criteria. White matter hyperintensity (WMH) volume, covert brain infarcts, hippocampal volume, and total cerebral brain volume were quantified. RESULTS: Baseline measures of WMH and hippocampal volume were associated with MCI status cross-sectionally and also with conversion from normal cognition to MCI at 6.5-year follow-up. Annualized change rates in total cerebral brain volume and hippocampal volume were associated with conversion from normal cognition to MCI to follow-up. DISCUSSION: Baseline WMH and hippocampal volume are markers that are both associated with conversion from normal cognition to MCI, highlighting the role of both vascular lesions and neurodegeneration in MCI. PMID- 28984641 TI - Prospects for adoptive T-cell therapy for invasive fungal disease. AB - PURPOSE OF REVIEW: Invasive fungal disease (IFD) is a cause of morbidity and mortality in allogeneic hematopoietic stem cell transplant (HSCT) recipients. As more potent broad-spectrum antifungal agents are used in prophylaxis, drug resistance and less common fungal species have increased in frequency. Here we review current treatments available for IFD and examine the potential for adoptive T-cell treatment to enhance current therapeutic choices in IFD. RECENT FINDINGS: There is growing evidence supporting the role of T cells as well as phagocytes in antifungal immunity. T cells recognizing specific antigens expressed on fungal morphotypes have been identified and the role of T-cell transfer has been explored in animal models. The clinical efficacy of adoptive transfer of antigen-specific T cells for prophylaxis and treatment of viral infections post-HSCT has raised interest in developing good manufacturing practice (GMP)-compliant methods for manufacturing and testing fungus-specific T cells after HSCT. SUMMARY: As the outcomes of IFD post-HSCT are poor, reconstitution of antifungal immunity offers a way to correct the underlying deficiency that has caused the infection rather than simply pharmacologically suppress fungal growth. The clinical development of fungus specific T cells is in its early stages and clinical trials are needed in order to evaluate safety and efficacy. PMID- 28984643 TI - Assessing Clinical Significance of Acute Kidney Injury in Burn Patients. PMID- 28984642 TI - Viral infections in solid organ transplant recipients: novel updates and a review of the classics. AB - PURPOSE OF REVIEW: To summarize new discoveries in viral pathogenesis and novel therapeutic and prophylactic strategies in organ transplant recipients. RECENT FINDINGS: For decades, prophylaxis of cytomegalovirus (CMV) has been the standard preventive strategy, but new clinical trials are expected to determine the advantages of preemptive therapy over prophylaxis. Novel anti-CMV agents, such as maribavir and letermovir, are being studied for the treatment of resistant/refractory CMV as alternatives to foscarnet and cidofovir. CMV immune monitoring may offer individualized management plans. Epstein-Barr virus infections in transplant recipients are difficult to prevent and treat, though recent data suggest possible merit to pretransplant rituximab among high-risk transplant recipients. We review the groundbreaking HIV-to-HIV organ transplant trials, which are expected to revolutionize the care of HIV-infected individuals. Finally, we review topical developments in human herpesvirus 8, Zika virus, RNA respiratory viruses, adenovirus, norovirus, and polyoma viruses in organ transplantation. SUMMARY: Ongoing trials to optimize CMV prophylaxis and treatment, and outcomes of HIV-to-HIV organ transplantation in the United States, have significant implications to optimize management of these viruses in transplant recipients. Assessment of new antivirals and antiviral strategies, such as adoptive immunotherapy, is warranted for refractory viral infections. PMID- 28984644 TI - Robotic Versus Laparoscopic Minimally Invasive Surgery for Rectal Cancer: A Systematic Review and Meta-analysis of Randomized Controlled Trials. AB - OBJECTIVE: The aim of this study was to evaluate the safety and efficacy of elective rectal resection for rectal cancer in adults by robotic surgery compared with conventional laparoscopic surgery. SUMMARY OF BACKGROUND DATA: Technological advantages of robotic surgery favor precise dissection in narrow spaces. However, the evidence base driving recommendations for the use of robotic surgery in rectal cancer primarily hinges on observational data. METHODS: We searched MEDLINE, Embase, and CENTRAL for randomized controlled trials (until August 2016) comparing robotic surgery versus conventional laparoscopic surgery. Data on the following endpoints were evaluated: circumferential margin status, mesorectal grade, number of lymph nodes harvested, rate of conversion to open surgery, postoperative complications, and operative time. Data were summarized as relative risks (RR) or weighted mean differences (WMDs) with 95% confidence intervals (95% CIs). Risk of bias of studies was assessed with standard methods. RESULTS: Five trials were eligible, including 334 robotic and 337 laparoscopic surgery cases. Meta-analysis showed that RS was associated with lower conversion rate (7.3%; 4 studies, 544 participants, RR 0.58; 95% CI 0.35-0.97, P = 0.04, I = 0%) and longer operating time (MD 38.43 minutes, 95% CI 31.84-45.01: P < 0.00001) compared with laparoscopic surgery. Perioperative mortality, rate of circumferential margin involvement (2 studies, 489 participants, RR 0.82, 95% CI 0.39-1.73), and lymph nodes collected (mean 17.4 Lymph Nodes; 5 trials, 674 patients, MD -0.35, 95% CI -1.83 to 1.12) were similar. The quality of the evidence was moderate for most outcomes. CONCLUSION: Evidence of moderate quality supports that robotic surgery for rectal cancer produces similar perioperative outcomes of oncologic procedure adequacy to conventional laparoscopic surgery. Robotic surgery portraits lower rate of conversion to open surgery, while operating time is significantly longer than by laparoscopic approach. PMID- 28984645 TI - Advances in the endoscopic management of gastric outflow disorders. AB - PURPOSE OF REVIEW: Disorders of gastric outflow and outlet obstruction include a variety of benign and malignant disorders such as peptic strictures, foreign bodies, gastroparesis, and cancers of the stomach, duodenum, and pancreas. Historically, a majority of patients presenting with gastric outlet obstruction (GOO) were to the result of peptic ulcers and surgical management of peptic ulcer complications was a mainstay of general surgical training. Invasive surgery is being performed less frequently today due to realization of the role of Helicobacter pylori in peptic ulcer disease and the introduction of novel endoscopic techniques for management of GOO. RECENT FINDINGS: For malignant GOO, the introduction of lumen-apposing metal stents have opened the door for the development and performance of endoscopic ultrasound-guided gastric bypass procedures. For benign GOO, including gastroparesis and pyloric stenosis, endoscopic myotomy shows promise. SUMMARY: Endoscopic ultrasound-guided gastric bypass, per-oral endoscopic myotomy, and other novel techniques in the endoscopic management of GOO, are discussed in this review. PMID- 28984646 TI - First trimester prediction and prevention of adverse pregnancy outcomes related to poor placentation. AB - PURPOSE OF REVIEW: To summarize recent research findings related to first trimester prediction and prevention of adverse pregnancy outcomes associated with poor placentation. Recent publications related to prediction and prevention of preeclampsia, intrauterine growth restriction (IUGR) and stillbirth were reviewed. RECENT FINDINGS: Researchers continue to identify markers that will help predict pregnancies that go on to develop preeclampsia through screening at 11-13 weeks. A number of multivariate algorithms describing risks for preeclampsia have been published and some of these have been validated in independent populations. A large randomized controlled trial has proven the efficacy of a first trimester prediction - prevention programme for preeclampsia with an 80% reduction in prevalence of disease leading to delivery less than 34 weeks. Screening tools for IUGR and stillbirth are less advanced and require further validation in other populations. The value of these models in preventing disease still needs to be demonstrated. SUMMARY: Significant progress has been made in developing predictive and preventive strategies which can affect the prevalence of severe early-onset preeclampsia. This approach could be adopted for population-based screening aiming to prevent this disease. PMID- 28984647 TI - Functional genomics of stromal cells in chronic inflammatory diseases. AB - PURPOSE OF REVIEW: Stroma is a broad term referring to the connective tissue matrix in which other cells reside. It is composed of diverse cell types with functions such as extracellular matrix maintenance, blood and lymph vessel development, and effector cell recruitment. The tissue microenvironment is determined by the molecular characteristics and relative abundances of different stromal cells such as fibroblasts, endothelial cells, pericytes, and mesenchymal precursor cells. Stromal cell heterogeneity is explained by embryonic developmental lineage, stages of differentiation to other cell types, and activation states. Interaction between immune and stromal cell types is critical to wound healing, cancer, and a wide range of inflammatory diseases. Here, we review recent studies of inflammatory diseases that use functional genomics and single-cell technologies to identify and characterize stromal cell types associated with pathogenesis. RECENT FINDINGS: High dimensional strategies using mRNA sequencing, mass cytometry, and fluorescence activated cell-sorting with fresh primary tissue samples are producing detailed views of what is happening in diseased tissue in rheumatoid arthritis, inflammatory bowel disease, and cancer. Fibroblasts positive for CD90 (Thy-1) are enriched in the synovium of rheumatoid arthritis patients. Single-cell RNA-seq studies will lead to more discoveries about the stroma in the near future. SUMMARY: Stromal cells form the microenvironment of inflamed and diseased tissues. Functional genomics is producing an increasingly detailed view of subsets of stromal cells with pathogenic functions in rheumatic diseases and cancer. Future genomics studies will discover disease mechanisms by perturbing molecular pathways with chemokines and therapies known to affect patient outcomes. Functional genomics studies with large sample sizes of patient tissues will identify patient subsets with different disease phenotypes or treatment responses. PMID- 28984648 TI - New treatment paradigms in spondyloarthritis. AB - PURPOSE OF REVIEW: The review presents the recent rapid expansion of therapeutical options in spondyloarthritis. Additionally, it focuses on the importance of additional questions raised by the growing therapeutic possibilities related to the optimal use of these drugs. RECENT FINDINGS: The emergence of new treatment options opens new avenues and opportunities for treating patients with nonresponse, contraindications, or intolerance for classic drugs. However, it becomes more relevant than ever to define not only drugs and treatment options but also treatment strategies. We address current literature and remaining questions on strategies such as early intervention, combination treatment, personalized medicine, and treat-to-target. SUMMARY: Not only the treatment as such, but also the treatment strategy is crucial to reveal the full therapeutic potential and benefit for patients. Whereas cautious but crucial steps have been taken in the last years to explore these aspects, related to timing and sequence of treatment (including combination treatments), stratified medicine approaches, and treat-to-target strategies, it is now time for full scale investment in prospective strategy trials. PMID- 28984649 TI - Orthostatic hypotension for the cardiologist. AB - PURPOSE OF REVIEW: Orthostatic hypotension is a phenomenon commonly encountered in a cardiologist's clinical practice that has significant diagnostic and prognostic value for a cardiologist. Given the mounting evidence associating cardiovascular morbidity and mortality with orthostatic hypotension, cardiologists will play an increasing role in treating and managing patients with orthostatic hypotension. RECENT FINDINGS: The American College of Cardiology, American Heart Association, and Heart Rhythm Society recently published consensus guidelines on the diagnosis, treatment, and management of syncope and their instigators, including orthostatic hypotension. Additionally, consensus guidelines have also been recently updated, reinforcing the universal definition orthostatic hypotension and its closely associated pathologies. Finally, the United States Food and Drug Administration (FDA) recently approved droxidopa, a synthetic oral norepinephrine prodrug, in 2014 for the treatment of neurogenic orthostatic hypotension (nOH), and it represents a well tolerated, effective, and easy to use intervention for nOH. This represents only the second drug approved by the FDA for orthostatic hypotension, the first being midodrine in 1986. A handful of smaller head-to-head studies have pitted not only pharmacologic agents to one another but also nonpharmacologic interventions to pharmacologic agents. Additionally, recent studies have also reported on more convenient screening tools for orthostatic hypotension. SUMMARY: Though there have been many advances in the management of orthostatic hypotension, nOH remains a chronic, debilitating, and often progressively fatal condition. Cardiologists can play a very important role in optimizing hemodynamics in this patient population to improve quality of life and minimize cardiovascular risk. PMID- 28984650 TI - Diagnosis and clinical management of long-QT syndrome. AB - PURPOSE OF REVIEW: To give an overview over the substantial advances in the diagnosis and management of Long-QT syndrome since its first description 60 years ago. RECENT FINDINGS: LQT syndrome remains the most common inherited arrhythmia and is a leading cause for sudden unexplained death accounting for up to 20-25% of cases. Rapid progress of genetic technology over the past 2 decades has significantly improved our understanding of molecular and genetic mechanisms of LQT. Despite all those novel insights, phenotype assessment and appropriate risk stratification in LQT remains challenging - even for the expert. SUMMARY: This review outlines our current understanding and approach to the clinical diagnosis and management of LQT as well as recent insights into genotype-phenotype correlations. Genetic testing has evolved beyond a pure diagnostic tool and is in addition increasingly integrated as complementary prognostic marker. With regard to the management of LQT, there is now evidence that the protective effect of beta-blockers is rather substance-specific than a class effect. Novel approaches in conjunction with standard beta-blockers - are emerging including gene specific treatment for certain subtypes of LQT. A specialized inherited arrhythmia clinic is the preferred resource for the complex risk stratification and individualized management of individuals with LQT. PMID- 28984651 TI - New anti-HER2 agents: from second-generation tyrosine kinases inhibitors to bifunctional antibodies. AB - PURPOSE OF REVIEW: HER2-positive breast cancers have benefited since the end of the twentieth century, not only from the improvement of biological knowledge, but also from major technological advances. The latter allowed the synthesis of the first generation of enzymatic inhibitors of the HER receptor family such as lapatinib, but above all, monoclonal antibodies such as trastuzumab or pertuzumab having profoundly modified the management of these cancers. However, despite outstanding progresses, there are still patients who are not cured with these first-generation treatments, and they will need new approaches to improve disease control and impact patients' survival. RECENT FINDINGS: Understanding the mechanisms of escape to these treatments, more than real resistance, has profoundly changed our pharmacological approaches. They have enabled the development of molecules blocking the signaling pathway downstream of receptors such as mTOR, PI3K inhibitors or molecules interacting with the cellular traffic of the receptor in combination with the first-generation treatments. In addition, new second-generation tyrosine kinase inhibitors have demonstrated increased in vitro efficacy, but still need to show clinical relevance because of new toxicity profiles. The antibody engineering had also permitted a paradigm evolution of the role of the antibody treatments, particularly with the synthesis of bispecific and trifunctional antibodies, promoting the link between the tumor and the immune system, with the goal to amplify the immune anticancer response. SUMMARY: Among the new anti-HER2 agents, second-generation tyrosine kinase inhibitors and bifunctional antibodies are promising approaches that will help to improve disease control and curability of HER2-positive breast cancers. PMID- 28984652 TI - An Outcomes Study on the Effects of the Singapore General Hospital Burns Protocol. AB - INTRODUCTION: The Singapore General Hospital Burns Protocol was implemented in May 2014 to standardize treatment for all burns patients, incorporate new techniques and materials, and streamline the processes and workflow of burns management. This study aims to analyze the effects of the Burns Protocol 2 years after its implementation. METHODS: Using a REDCap electronic database, all burns patients admitted from May 2013 to April 2016 were included in the study. The historical preimplementation control group composed of patients admitted from May 2013 to April 2014 (n = 96). The postimplementation prospective study cohort consisted of patients admitted from May 2014 to April 2016 (n = 243). Details of the patients collected included age, sex, comorbidities, total body surface area (TBSA) burns, time until surgery, number of surgeries, number of positive tissue and blood cultures, and length of hospital stay. RESULTS: There was no statistically significant difference in the demographics of both groups. The study group had a statistically significant shorter time to surgery compared with the control group (20.8 vs 38.1, P < 0.0001). The study group also averaged fewer surgeries performed (1.96 vs 2.29, P = 0.285), which, after accounting for the extent of burns, was statistically significant (number of surgeries/TBSA, 0.324 vs 0.506; P = 0.0499). The study group also had significantly shorter length of stay (12.5 vs 16.8, P = 0.0273), a shorter length of stay/TBSA burns (0.874 vs 1.342, P = 0.0101), and fewer positive tissue cultures (0.6 vs 1.3, P = 0.0003). The study group also trended toward fewer positive blood culture results (0.09 vs 0.35, P = 0.0593), although the difference was just shy of statistical significance. CONCLUSIONS: The new Singapore General Hospital Burns Protocol had revolutionized Singapore burns care by introducing a streamlined, multidisciplinary burns management, resulting in improved patient outcomes, lowered health care costs, and improved system resource use. PMID- 28984653 TI - Comparative Outcomes of Inferior Pedicle and Superomedial Pedicle Technique With Wise Pattern Reduction in Gigantomastic Patients. AB - INTRODUCTION: Although multiple pedicle and skin excision techniques exist for gigantomastic breast reduction, no consensus exists as to which method is most effective in providing an aesthetically pleasing breast, especially in the long term period. This study aimed to compare the aesthetic and surgical outcomes between inferior pedicle and superomedial pedicle reductions, which both use Wise pattern skin excision in gigantomastic patients. METHODS: A prospective study was planned, and the number of patients was determined before the beginning of the study. Fifty inferior pedicle breast reductions (25 patients) were matched to 50 superomedial pedicle breast reductions (25 patients) after a 1-year postoperative period. Matching was done based on age, body mass index, size of reduction, minor and major postoperative complications, symptomatic relief, long-term measurements of the nipple-areola complex position, and inferior pole length elongation at 1 year postoperatively. RESULTS: There was no significant difference in complications between the inferior and superomedial pedicle groups. The mean resection weight was 1320 (right) and 1355 g (left) in the inferior pedicle group and 1380 (right) and 1310 g (left) in the superomedial pedicle group (P < 0.05). The mean elongation of the nipple-areola complex to inframamarian fold distance was 1.97 (right) and 2.19 cm (left) in the inferior pedicle group and 2.15 (right) and 2.26 cm (left) in the superomedial pedicle group (P < 0.05). At 1 year postoperatively, the mean suprasternal notch to nipple distance was 22.10 (right) and 22.33 cm (left) in the inferior pedicle group and 22.90 (right) and 22.14 cm (left) in the superomedial pedicle group (P < 0.05). All patients achieved symptomatic relief. DISCUSSION: This study shows that the inferior pedicle is not superior to the superomedial pedicle technique with Wise patern skin excision in gigantomastic patients. Although both pedicle techniques generate acceptable aesthetic outcomes, bottoming-out has occurred in each of the groups with time. To prevent this deformity, some pedicle modifications may be required. PMID- 28984654 TI - Joint Denervation in the Digits: Technique and Patient Satisfaction. AB - BACKGROUND: Traditional approaches to treating painful osteoarthritis of the fingers include arthrodesis and arthroplasty. Although highly effective for pain control, arthrodesis sacrifices joint motion and can be complicated by nonunion, malunion, and infection.Implant arthroplasty preserves motion but is likewise subject to complications-particularly at the level of the proximal interphalangeal joint. In contrast, finger joint denervation is a simple outpatient procedure that maintains joint motion. In this study, we describe our surgical techniques for joint denervation and review our survey of patient satisfaction. METHODS: A retrospective review was performed of all patients undergoing finger joint denervation for osteoarthritis at our institution from 2012 to 2014. Each patient was contacted by phone and asked to rate their pre- and postoperative pain and function.Patients were also asked about any complications experienced and if they would choose to undergo the operation again. RESULTS: Over the 2-year period, 12 patients underwent denervation of 23 joints. Of the 12 patients in the study, 11 undergoing 22 joint denervations were available for our survey. Patient-reported pain scores fell from a median of 5/5 preoperatively to 0/5 after recovery (P < 0.001). Perceived hand function improved from a preoperative reported median of 2/5 to a postoperative median of 5/5 (P < 0.001). Complications were few, and 9 of 11 patients said they would choose to have the operation again. CONCLUSIONS: Joint denervation is a safe and effective treatment modality for osteoarthritis of the digits, resulting in good pain relief and high patient satisfaction with low complication rates. PMID- 28984655 TI - Mixed Versus Pure Variants of Desmoplastic Melanoma: The Cleveland Clinic Experience. AB - BACKGROUND: Desmoplastic melanoma (DM) is a subvariant of spindle cell melanoma, accounting for less than 4% of all cutaneous melanomas. It occurs later in life and is associated with chronic sun exposure. Desmoplastic melanoma prognosis is considered more favorable than other variants, with lower rates of metastasis and higher survival. Recently, DM has been further subclassified into pure and mixed, calling into question surgical management and patient outcomes as well as viability of current nationwide databases without this distinction. METHODS: We identified all patients with a histopathologic diagnosis of DM from the Cleveland Clinic electronic melanoma database (n = 58) from 1997 to 2013. Clinical and histopathologic data were collected. Comparison in clinical variables was performed between patients who had pure (n = 15) and mixed (n = 43) variants of DM. RESULTS: There were no differences in age, sex, location of lesion, Breslow depth, ulceration, or regression. Patients with mixed DM were more likely to have lymphovascular invasion (P = 0.03) compared with pure DM. There was no difference in performance of sentinel lymph node biopsy (P = 0.25) or sentinel lymph node positivity (P = 0.31) between the 2 groups. Recurrence was present in 13.3% of pure and 30.2% of mixed patients. Overall, Kaplan-Meier 3-year survival was 75% for pure and 80% for mixed DM (P = 0.53). CONCLUSIONS: Pure and mixed DMs seem to have similar clinical characteristics and outcomes. This indicates that analysis of national datasets without this subclassification remains viable. PMID- 28984656 TI - The Distally Based Peroneus Brevis Flap: The 5-Step Technique. AB - The peroneus brevis flap was first described as proximally based by Mathes et al (Surg Clin North Am. 1974;54:1337-1354) and later by Jackson and Scheker (Injury. 1982;13:324-330). A distally based version of this flap by Mathes and Nahai (Reconstructive Surgery: Principles, Anatomy and Technique. 1997:1437e46) was subsequently described in 1997. The first case series of distally based flaps was published by Eren et al (Plast Reconstr Surg. 2001;107:1443-1448). In our experience, the distally based flap is a useful muscle flap to reconstruct small defects in the lateral distal third of the leg. Initial interest and confidence in the use of this flap in our unit were hindered by lack of direct experience and descriptive detail in the literature. We have now developed a systematic approach to harvest the distally pedicled peroneus brevis muscle flap in 5 reproducible, safe steps. This has allowed the flap to become adopted as a standard technique of limb reconstruction in our unit with no cases of flap loss. PMID- 28984657 TI - Osseointegrated Prosthetic Ear Reconstruction in Cases of Skin Malignancy: Technique, Outcomes, and Patient Satisfaction. AB - BACKGROUND: Ear reconstruction with osseointegrated prosthetic implants is a well established method of reconstruction after resection of skin malignancies on the external ear. There is limited literature reporting technique, outcomes, and patient satisfaction. METHODS: We evaluated our outcomes over a 5-year period looking at osseointegrated prosthetic reconstruction after auriculectomy for external ear skin malignancies. We report demographics, disease characteristics, technique, and complications. The patients were surveyed looking at 6 domains: satisfaction, stability, comfort, ease of use, level of self-consciousness, and preoperative education. RESULTS: Of the 21 patients included in the study, 14 (67%) were treated for invasive melanoma (Breslow depth, >0.8mm), 4 (19%) for squamous cell carcinoma, 2 (10%) for basal cell carcinoma, and 1 (5%) for an atypical fibroxanthoma. Complications rates were low. There were no cases of infection, hematoma, or bleeding. In 2 patients (9.5%), 1 of the 3 implants failed to osseointegrate and was removed, but the prosthesis was able to be secured with the remaining 2 posts. There were 3 cases (14%) of delayed healing and 1 with excessive granulation tissue growth. Survey results showed high satisfaction in all measured domains. CONCLUSIONS: In cases of skin malignancy requiring total or subtotal auriculectomy, prosthetic ear reconstruction with osseointegrated implants is a good alternative to reconstruction with autologous tissue. Our experience demonstrates good outcomes and with low complication rates and high patient satisfaction. PMID- 28984658 TI - Long-term Outcomes After Flap Reconstruction in Pediatric Pressure Ulcers. AB - BACKGROUND: Pressure ulcers refractory to nonoperative management may undergo flap reconstruction. This study aims to evaluate the long-term outcomes and recurrence rates of flap reconstruction for pediatric pressure ulcers. METHODS: We reviewed the records of patients who underwent flap reconstruction for pressure ulcer(s) from 1995 to 2013. RESULTS: Twenty-four patients with 30 pressure ulcers, requiring 52 flaps were included. Ulcers were stages III and IV and mostly involved either the ischia (15/30) or sacrum (8/30). Flaps were followed for a median of 4.9 years. Twenty-three patients were wheelchair dependent, and 20 had sensory impairment at their ulcer site(s). Ten patients had a history of noncompliance with preoperative management, 8 of whom experienced ulcer recurrence. Twenty-one ulcers had underlying osteomyelitis, associated with increased admissions (P = 0.019) and cumulative length of stay (P = 0.031). Overall, there was a 42% recurrence rate in ulceration after flap reconstruction. Recurrence was associated with a preoperative history of noncompliance with nonoperative therapy (P = 0.030), but not with flap type or location, age, sex, body mass index, osteomyelitis, or urinary/fecal incontinence (P > 0.05, all). CONCLUSIONS: Flap reconstruction can be beneficial in the management of pediatric pressure ulcers. Although high rates of long-term success with this intervention have been reported in children, we found rates of ulcer recurrence similar to that seen in adults. Poor compliance with nonoperative care and failure to modify the biopsychosocial perpetuators of pressure ulcers will likely eventuate in postoperative recurrence. Despite the many comorbidities observed in our patient sample, compliance was the best indicator of long-term skin integrity and flap success. PMID- 28984659 TI - A Cross-Sectional Study of Variations in Reimbursement for Breast Reconstruction: Is A Healthcare Disparity On the Horizon? AB - BACKGROUND: Despite growing demand for breast reconstruction, financial disincentives to perform breast reconstruction in patients with government sponsored insurance plans may lead to longer wait times and decreased access to care. We identify the variation in reimbursement for implant and autologous reconstruction as a step toward understanding these financial implications, to develop safeguards to minimize effects on access to care. METHODS: Billing data were collected over a 10-year period for patients undergoing implant-based (19357) or free-flap (19364) breast reconstruction. Patients were placed into cohorts according to insurance type-Medicare, Medicaid, or private insurance, and these were directly compared. RESULTS: A total of 2691 women underwent breast reconstruction between 2003 and 2013; 71.2% had private insurance, 13.3% had Medicaid, and 14.49% had Medicare. For implant-based reconstructions, the average reimbursement of total charges was 16.3% for Medicaid, 28.3% for Medicare, and 67.2% for private insurance. For autologous reconstruction, average reimbursement was 12.37% for Medicaid, 22.9% for Medicare, and 35.35% for private insurance. Hourly reimbursement estimates for Medicaid patients undergoing autologous reconstruction were lowest. The highest hourly reimbursement estimate was for privately insured patients undergoing implant-based reconstruction. Over time, reimbursement for autologous reconstruction has declined significantly for all payor types, whereas implant-based reimbursement disparities are narrowing. CONCLUSIONS: We found that wide variations in reimbursement for breast reconstruction procedures exist and may preclude some surgeons from offering certain reconstructive options to a subset of patients. Understanding these discrepancies is a key first step in minimizing a potential care delivery disparity for this patient population. PMID- 28984660 TI - Selective Scalp Nerve Block: A Useful Technique With Tissue Expansion in Postburn Pediatric Alopecia. AB - BACKGROUND: Scalp defects can be reconstructed either with skin graft, local flaps, free flaps, or tissue expansion. Tissue expanders have been proved to be fruitful in the pediatric population. Scalp expansion has proved to be useful in the reconstruction of posttraumatic and postburn alopecic defects. Selective nerve block can be added for attenuation of sympathetic stimulation and decrease surgical stress in cranial surgeries. In this study, a comparison was done between using selective nerve block and without selective nerve block in both stages of tissue expansion procedure. PATIENTS AND METHODS: This study included 32 different children who underwent tissue expansions in the management of postburn alopecia. Pediatric patients presented with postburn alopecia of the scalp with mature scar were included in this work. RESULTS: Postoperative analgesics were less in children who had received scalp block, whereas it was shorter in patients who did not receive any scalp block. Meperidine consumption was much more less in patients who received selective scalp nerve block. Pain score was markedly decreased in children who had received selective scalp nerve block in the immediate postoperative period. Children who received scalp block showed marked attenuation in the surgical stress responses with minimal changes in heart rate and mean arterial blood pressure after skin incision. CONCLUSIONS: Scalp nerve block is considered an excellent choice for postoperative pain control with less need for opioid analgesia. PMID- 28984661 TI - Surgeon-Controlled Comparison of Direct-to-Implant and 2-Stage Tissue Expander Implant Immediate Breast Reconstruction Outcomes. AB - BACKGROUND: Current literature comparing outcomes of immediate breast reconstruction using direct-to-implant (DTI) single-stage and 2-stage tissue expanders (TEs) is conflicting. This study compared overall outcomes and determined predictive patient factors associated with higher complication rates. METHODS: After institutional review board approval, a retrospective cohort study of consecutive patients who underwent immediate breast reconstruction from 2010 to 2014 at a single hospital was performed. Demographic data and complications were recorded and compared using univariate analysis. Infection was defined as any patient receiving antibiotics beyond the expected postoperative course or restarting antibiotics for a suspected infection. RESULTS: Seventy-nine breasts (50 patients) underwent immediate breast reconstruction using tissue expansion, and 117 breasts (69 patients) underwent immediate breast reconstruction using the DTI technique. Overall complications, infection rate, and rate of aesthetic revisions were higher in the TE group compared with the DTI group. There was no difference in rates of seroma, hematoma, and mastectomy skin flap necrosis between the 2 groups. Infectious complications were significantly higher in patients with body mass index of greater than 30 who underwent TE-based reconstruction than those who underwent DTI-based reconstruction. CONCLUSIONS: Single-stage DTI immediate breast reconstruction has less overall complications than 2-stage TE-based immediate reconstruction. Direct-to-implant immediate breast reconstruction may provide favorable outcomes in patients with body mass index of greater than 30. PMID- 28984662 TI - Rapid cardiothoracic ultrasound protocol for diagnosis of acute heart failure in the emergency department. AB - OBJECTIVES: The aim of this study was to evaluate the performance of a rapid cardiothoracic ultrasound protocol (CaTUS), combining echocardiographically derived E/e' and lung ultrasound (LUS), for diagnosing acute heart failure (AHF) in patients with undifferentiated dyspnea in an emergency department (ED). PATIENTS AND RESULTS: We enrolled 100 patients with undifferentiated dyspnea from a tertiary care ED, who all had CaTUS done immediately upon arrival in the ED. CaTUS was positive for AHF with an E/e' > 15 and congestion, that is bilateral B lines or bilateral pleural fluid, on LUS. In addition, an inferior vena cava index was also recorded to analyze whether including a central venous pressure estimate would add diagnostic benefit to the CaTUS protocol. All 100 patients had a brain natriuretic peptide (BNP) sample withdrawn, and 96 patients underwent chest radiography in the ED, which was analyzed later by a blinded radiologist. The reference diagnosis of AHF consisted of either a BNP of more than 400 ng/l or a BNP of less than 100 ng/l in combination with congestion on chest radiography and structural heart disease on conventional echocardiography.CaTUS had a sensitivity of 100% (95% confidence interval: 91.4-100%), a specificity of 95.8% (95% confidence interval: 84.6-99.3%), and an area under the curve of 0.979 for diagnosing AHF (P<0.001). The diagnostic accuracy of CaTUS was higher than of either E/e' or LUS alone. Adding the inferior vena cava index to CaTUS did not improve diagnostic accuracy. CaTUS seemed helpful also for differential diagnostics of dyspnea, mainly regarding pneumonias and pulmonary embolisms. CONCLUSION: CaTUS, combining E/e' and LUS, provided excellent accuracy for diagnosing AHF. PMID- 28984663 TI - Practical management of concomitant acute heart failure and worsening renal function in the emergency department. AB - Worsening renal function (i.e. any increase in creatinine or decrease in the estimated glomerular filtration rate) is common in patients admitted for acute heart failure in the emergency department. Although worsening renal function (WRF) has been associated with the occurrence of dismal outcomes, this only appears to be the case when associated with clinical deterioration. However, if the clinical status of the patient is improving, a certain increase in serum creatinine may be acceptable. This WRF, which is not associated with clinical deterioration or adverse outcomes (e.g. during treatment up-titration), has been referred to as 'pseudo-WRF' and should not detract clinicians from targeting 'guideline-recommended' therapies. This is an important message for emergency physicians to pursue diuretics as long as signs of pulmonary congestion persist to improve the clinical status of the patient. In the present review, we aim to provide clinicians in acute settings with an integrative and comprehensive approach to cardiorenal interactions in acute heart failure. PMID- 28984664 TI - Effect of 2 Different Drilling Speeds on the Osseointegration of Implants Placed With Flapless Guided Surgery: A Study in Rabbits. AB - OBJECTIVE: The aim of this study was to evaluate the influence of the drilling speed on bone healing and the osseointegration of implants placed with a guided flapless surgical technique in rabbit tibias. METHODS: For the evaluation of bone healing, a total of 30 perforations (defects) were made in both tibias of 15 rabbits using 2 different drilling speeds (1500 rpm-control group; 50 rpm-test group). The regeneration of bone tissue in the surgical sites was evaluated at 0, 7, and 14 days. For the evaluation of implant osseointegration, another 15 rabbits underwent drilling in both tibias for implant placement. Thirty implants (3.75 * 10 mm) were placed to evaluate osseointegration at 4, 8, and 12 weeks after surgery. RESULTS: Both groups showed a progressive healing of the defect, which involved the complete closure of the perforation. The osseointegration occurred in all groups with no statistically significant differences in the assessment of the osseointegration between the groups. CONCLUSION: In the experimental models used, the drilling speed does not prejudice the pattern of bone healing and osseointegration of implants placed with guided flapless surgery. PMID- 28984665 TI - Westchester Medical Center and Its Health Care System: One Hundred Years (1917 2017) of Dedicated Service to Community, Country, and Cardiology. PMID- 28984666 TI - Adrian Kantrowitz, MD (1918-2008) and His Contributions to Cardiac Transplantation. PMID- 28984667 TI - Ascending Aortic Aneurysm Is an Inherited Disease: A Contemporary Literature Review Based on Hill's Criteria of Specificity, Strength of Association, and Biological Coherence. AB - There is growing evidence of a differential etiological basis for thoracic aortic aneurysms (TAA), with ascending (As) TAAs being genetically mediated and descending (Des) TAAs more strongly related to acquired pathologies. A comprehensive literature review of this hypothesis has not been carried out. We carried out a systematic literature review based on the latest guidelines on TAA endorsed by the American Heart Association. The etiologies were classified as genetic and inherited, the studies were tabulated accordingly, and Hill's epidemiological criteria of causality were applied. We found 38 studies addressing the etiology of TAAs. Out of these, 17 were about genetic causes, 9 about acquired causes, and 4 had information regarding both etiologies. Multiple genetic studies showed a strong association of As TAA with different genetic mutations. Contrary to commonly held beliefs, acquired causes, that is, dyslipidemia, diabetes, and atherosclerosis, were negatively associated with As TAA and positively associated with Des TAA. Hypertension was only associated with Des TAA and dissections (TAAD), not with As TAA. Multiple studies fulfilled the criteria of strength of association (n = 4), consistency (n = 9), specificity (n = 5), temporality (24), biological gradient (n = 3), plausibility (n = 38), biological coherence (n = 25), experiment (n = 4), and analogy (n = 6). Our literature review supports the hypothesis that As TAA is genetically mediated and Des TAA is predominantly an acquired pathology, and supports the argument for genetic testing in all cases of As TAA. PMID- 28984668 TI - Brain-Heart Interactions in Traumatic Brain Injury. AB - The cardiovascular manifestations associated with nontraumatic head disorders are commonly known. Similar manifestations have been reported in patients with traumatic brain injury (TBI); however, the underlying mechanisms and impact on the patient's clinical outcomes are not well explored. The neurocardiac axis theory and neurogenic stunned myocardium phenomenon could partly explain the brain-heart link and interactions and can thus pave the way to a better understanding and management of TBI. Several observational retrospective studies have shown a promising role for beta-adrenergic blockers in patients with TBI in reducing the overall TBI-related mortality. However, several questions remain to be answered in clinical randomized-controlled trials, including population selection, beta blocker type, dosage, timing, and duration of therapy, while maintaining the optimal mean arterial pressure and cerebral perfusion pressure in patients with TBI. PMID- 28984669 TI - Vitamins for Cardiovascular Diseases: Is the Expense Justified? AB - Despite the knowledge that a well-balanced diet provides most of the nutritional requirements, the use of supplemental vitamins is widespread among adults in the United States. Evidence from large randomized controlled trials over the last 2 decades does not support vitamin supplementation for the reduction of cardiovascular risk factors or clinical outcomes. Many of the vitamins used in common practice likely are safe when consumed in small doses, but long-term consumption of megadoses is not only expensive but has the potential to cause adverse effects. Therefore, a need exists to revisit this issue, reminding the public and healthcare providers about the data supporting the use of vitamins for cardiovascular disease, and the potential for harm and the expense associated with their unnecessary use. In this review, we highlight the scientific evidence from randomized controlled studies regarding the efficacy and safety of vitamin supplementation for primary and secondary prevention of cardiovascular diseases and outcomes. We also draw attention to issues related to widespread and indiscriminate use of vitamin supplements and the need to educate the public to curtail unnecessary consumption and expense by limiting their use based on strong scientific evidence. PMID- 28984670 TI - Neprilysin Inhibition and the Treatment of Heart Failure: Recent Steps in the Right Direction. AB - Numerous investigators have attempted to target the natriuretic peptide system in the treatment of heart failure since it was first described over 30 years ago. The history of neprilysin inhibition as a treatment for heart failure has been characterized by numerous setbacks. Recently, the PARADIGM-HF trial has shown favorable results, which may bring neprilysin inhibition into the mainstream of clinical practice. This article will review the history of the natriuretic peptide system and the investigations into it as a target for heart failure treatment, culminating in the positive results of the PARADIGM-HF trial, as well as planned and potential future directions for research. PMID- 28984671 TI - Early Coronary Angiography for Survivors of Out-of-Hospital Cardiac Arrests Without ST Elevation. AB - There are over 300,000 out-of-hospital cardiac arrests (OOHCA) in the United States each year, and the long-term survival rate is less than 10%. Despite improvements in postarrest management, the greatest drop-off in survival occurs during hospitalization, mostly due to myocardial dysfunction and neurological injury. Coronary artery disease is common in postcardiac arrest patients, with an incidence of approximately 60-80%. In patients with a chest pain syndrome and an ST-segment-elevation myocardial infarction pattern evident on the presenting electrocardiogram, immediate revascularization is recommended by cardiovascular societies due to established mortality benefits. However, it is less clear whether immediate or urgent coronary angiography for OOHCA survivors without ST elevation on the presenting electrocardiogram is beneficial. The current evidence base suggests that many OOHCA survivors, particularly when an acute coronary event is suspected, stand to benefit from early coronary angiography, although prospective trial data are lacking. Further studies are needed to identify whether all or even a subset of OOHCA survivors without ST elevation should undergo routine early coronary angiography. PMID- 28984672 TI - Cholangitis Lenta: A Clinicopathologic Study of 28 Cases. AB - Cholangitis lenta, also known as ductular cholestasis, cholangiolar cholestasis, or subacute nonsuppurative cholangitis, is an uncommon type of cholangitis characterized by ductular reaction with inspissated bile in dilated ductules. The literature on this unique entity has been limited to only a few studies based on a very limited number of cases, which importantly suggest an association with sepsis and/or intra-abdominal infection. The clinical, laboratory, and histologic features of 28 cases of cholangitis lenta are herein investigated. Twenty-five (89.3%) patients were liver transplant recipients. Most notably, the majority of patients showed clinical signs and symptoms of sepsis, and positive microbiology cultures were demonstrated in 24 (85.7%) patients. Significantly, 15 (53.6%) patients died during their hospitalization, ranging from 2 days to 5 months after the initial liver biopsy that showed histologic features of cholangitis lenta. Among the 13 discharged patients, including 2 who received retransplantation, 4 (14.3%) subsequently died of pneumonia, graft dysfunction, or fungal infection within 7 months to 9.3 years. Only 9 (32.1%) patients were alive at the last follow-up, with the follow-up time ranging from 3.8 to 10.4 years. Our data show that the finding of cholangitis lenta on liver biopsy is thus frequently associated with sepsis and with a high mortality rate. Therefore, accurate diagnosis of this condition on liver biopsy is imperative as it is an indication that the patient may have a potentially life threatening condition that requires immediate medical attention and management. PMID- 28984673 TI - Toward Biological Subtyping of Papillary Renal Cell Carcinoma With Clinical Implications Through Histologic, Immunohistochemical, and Molecular Analysis. AB - Papillary renal cell carcinoma (PRCC) has 2 histologic subtypes. Almost half of the cases fail to meet all morphologic criteria for either type, hence are characterized as PRCC not otherwise specified (NOS). There are yet no markers to resolve the PRCC NOS category. Accurate classification can better guide the management of these patients. In our previous PRCC study we identified markers that can distinguish between the subtypes. A PRCC patient cohort of 108 cases was selected for the current study. A panel of potentially distinguishing markers was chosen from our previous genomic analysis, and assessed by immunohistochemistry. The panel exhibited distinct staining patterns between the 2 classic PRCC subtypes; and successfully reclassified the NOS (45%) cases. Moreover, these immunomarkers revealed a third subtype, PRCC3 (35% of the cohort). Molecular testing using miRNA expression and copy number variation analysis confirmed the presence of 3 distinct molecular signatures corresponding to the 3 subtypes. Disease-free survival was significantly enhanced in PRCC1 versus 2 and 3 (P=0.047) on univariate analysis. The subtypes stratification was also significant on multivariate analysis (P=0.025; hazard ratio, 6; 95% confidence interval, 1.25-32.2). We propose a new classification system of PRCC integrating morphologic, immunophenotypical, and molecular analysis. The newly described PRCC3 has overlapping morphology between PRCC1 and PRCC2, hence would be subtyped as NOS in the current classification. Molecularly PRCC3 has a distinct signature and clinically it behaves similar to PRCC2. The new classification stratifies PRCC patients into clinically relevant subgroups and has significant implications on the management of PRCC. PMID- 28984674 TI - Targeted Genomic Profiling Reveals Recurrent KRAS Mutations in Mesonephric-like Adenocarcinomas of the Female Genital Tract. AB - Mesonephric adenocarcinoma most commonly arises in the cervix and is presumed to be derived from normal or hyperplastic mesonephric remnants. It is characterized by recurrent KRAS mutations and lack of PIK3CA/PTEN alterations. Adenocarcinomas of the uterine corpus and ovary characterized by morphologic and immunophenotypic similarities to mesonephric adenocarcinoma have been reported. The pathogenesis of these tumors, which have been designated "mesonephric-like adenocarcinomas" is unknown, and it has been debated whether these represent mesonephric adenocarcinomas that arise in the endometrium/ovary or endometrioid adenocarcinomas that closely mimic mesonephric adenocarcinoma. The relationship at the molecular level between mesonephric adenocarcinomas and mesonephric-like adenocarcinomas is unknown. The aim of this study was to examine the molecular alterations in mesonephric-like adenocarcinomas to identify driver mutations and potential therapeutically targetable mutations, and to determine the relationship between mesonephric-like adenocarcinomas and mesonephric adenocarcinomas using targeted next-generation sequencing. Seven mesonephric-like adenocarcinomas (4 ovarian, 3 uterine corpus) underwent targeted next-generation sequencing to detect mutations, copy number variations and structural variants in exonic regions of 300 cancer genes, and 113 selected intronic regions across 35 genes. All 7 tumors (100%) harbored canonical activating KRAS mutations (4 G12D, 3 G12V). PIK3CA activating mutations were identified in 3 of 7 (43%) cases. There were no alterations in PTEN, ARID1A, or TP53 in any of the tumors. In copy number analysis, 5 of 7 (71%) tumors exhibited 1q gain, which was accompanied by 1p loss in 2 cases. In addition, 4 of 7 (57%) tumors had chromosome 10 gain, which was accompanied by gain of chromosome 12 in 3 cases. Mesonephric-like adenocarcinomas, similar to mesonephric adenocarcinomas, are characterized by recurrent KRAS mutations, gain of 1q, lack of PTEN mutations, and gains of chromosomes 10 and 12. PIK3CA mutations, which have not previously been identified in mesonephric adenocarcinoma, were found in 3 of 7 (43%) mesonephric like adenocarcinomas in our study. Mesonephric-like adenocarcinomas exhibit strikingly similar molecular aberrations to mesonephric adenocarcinomas, but also frequently harbor PIK3CA mutations, demonstrating biological overlap with carcinomas of both mesonephric and Mullerian (endometrioid) differentiation. Given the previously documented association with endometriosis (ovarian neoplasms) and the prominent endometrial involvement (uterine corpus neoplasms), we believe these are best regarded as of Mullerian origin and representing adenocarcinomas which differentiate along mesonephric lines; as such, we propose the term mesonephric-like Mullerian adenocarcinoma. PMID- 28984675 TI - Feasibility of Prostate PAXgene Fixation for Molecular Research and Diagnostic Surgical Pathology: Comparison of Matched Fresh Frozen, FFPE, and PFPE Tissues. AB - Advances in prostate cancer biology and diagnostics are dependent upon high fidelity integration of clinical, histomorphologic, and molecular phenotypic findings. In this study, we compared fresh frozen, formalin-fixed paraffin embedded (FFPE), and PAXgene-fixed paraffin-embedded (PFPE) tissue preparation methods in radical prostatectomy prostate tissue from 36 patients and performed a preliminary test of feasibility of using PFPE tissue in routine prostate surgical pathology diagnostic assessment. In addition to comparing histology, immunohistochemistry, and general measures of DNA and RNA integrity in each fixation method, we performed functional tests of DNA and RNA quality, including targeted Miseq RNA and DNA sequencing, and implemented methods to relate DNA and RNA yield and quality to quantified DNA and RNA picogram nuclear content in each tissue volume studied. Our results suggest that it is feasible to use PFPE tissue for routine robot-assisted laparoscopic prostatectomy surgical pathology diagnostics and immunohistochemistry, with the benefit of significantly improvedDNA and RNA quality and RNA picogram yield per nucleus as compared with FFPE tissue. For fresh frozen, FFPE, and PFPE tissues, respectively, the average Genomic Quality Numbers were 7.9, 3.2, and 6.2, average RNA Quality Numbers were 8.7, 2.6, and 6.3, average DNA picogram yields per nucleus were 0.41, 0.69, and 0.78, and average RNA picogram yields per nucleus were 1.40, 0.94, and 2.24. These findings suggest that where DNA and/or RNA analysis of tissue is required, and when tissue size is small, PFPE may provide important advantages over FFPE. The results also suggest several interesting nuances including potential avenues to improve RNA quality in FFPE tissues and confirm recent suggestions that some DNA sequence artifacts associated with FFPE can be avoided. PMID- 28984676 TI - Advances in understanding and management of lymphoedema (cancer, primary). AB - PURPOSE OF REVIEW: Despite being neglected both clinically and in research in the past, primary lymphoedema, and lymphoedema secondary to cancer treatment have been the subject of an increasing number of studies in recent years. This review will focus on new developments relevant to clinical practice. RECENT FINDINGS: The main themes covered by the review include the incidence and prevalence of lymphoedema, early detection and intervention in cancer-related lymphoedema, risk reduction for the development of cancer-related lymphoedema, surgical treatment, palliative care for lymphoedema in advanced cancer and developments in the genetics of primary lymphoedema. SUMMARY: Evidence suggests that lymphoedema is more common than has been previously recognized. It continues to be a significant problem for people following cancer treatment. Developments in the early detection and treatment of cancer-related lymphoedema should reduce the future impact for patients. Advice on how to reduce the risk of developing lymphoedema may need to be modified in light of recent research. New treatments such as surgical procedures are still in their infancy but the results seem encouraging for selected patients. PMID- 28984677 TI - Advances in the understanding and management of mucositis during stem cell transplantation. AB - PURPOSE OF REVIEW: Mucositis is a severe and common side effect of anticancer treatments, with an incidence of between 40 and 80% depending on the cytotoxic regimen used. The most profound mucositis burden is experienced during conditioning regimens for hematopoietic stem cell transplant (HSCT), where the use of highly mucotoxic agents with or without total body irradiation leads to serious damage throughout the alimentary tract. Currently, the assessment and management of both oral and gastrointestinal mucositis lack authoritative guideline, with recommendations only achieved in narrow clinical scenarios. This review provides a brief overview of current management guidelines for mucositis in both adult and pediatric patients receiving HSCT, highlights recent advances in mucositis prevention and discusses future research avenues. RECENT FINDINGS: The Multinational Association of Supportive Care in Cancer and International Society for Oral Oncology (MASCC/ISOO) guidelines for the prevention of mucositis in HSCT are scarce, with low level laser therapy (photobiomodulation) and palifermin only recommended for oral mucositis. Loperamide and octreotide remain gold-standard for the treatment of diarrhea, despite poor efficacy. Although several interventions have been trialled in pediatric cohorts, no recommendations currently exist for children receiving high-dose chemotherapy or total body irradiation for HSCT. SUMMARY: HSCT continues to be associated with mucositis, which impacts on patients' ability and willingness to receive engraftment, and worsens clinical outcome. Research into the prevention and treatment of mucositis in this setting remains limited, with an overwhelming amount of small, single center studies that fail to achieve a sufficient level of evidence that warrant recommendation(s). As such, our ability to manage mucotoxic side effects of high dose chemotherapy and irradiation is limited, particularly in children. PMID- 28984678 TI - Effect of branched-chain amino acid supplements on muscle strength and muscle mass in patients with liver cirrhosis. AB - OBJECTIVE: The aim of this study was to assess the effect of branched-chain amino acid (BCAA) supplements on muscle strength and muscle mass in patients with liver cirrhosis. PATIENTS AND METHODS: We carried out a single-center, prospective study of adult cirrhotic patients receiving nutrition therapy at Shonan Kamakura General Hospital. A 28-day pretreatment observation period was followed by a 24 week treatment period. Patients who fulfilled the treatment criteria received one package of oral BCAA supplement powder twice a day and the response was evaluated. A responder to BCAA in muscle strength and muscle mass was defined as a patient with an increased skeletal muscle mass index and hand grip assessed 24 weeks after drug treatment commenced. RESULTS: Eighty-two patients fulfilled our criteria and completed the treatment. In terms of muscle strength, there were 59 (72.0%) responders to BCAA supplementation with a significant increase in hand grip from before treatment (22.2+/-6.3 kg) to after treatment (23.9+/-6.4 kg) (P<0.001). In terms of muscle mass, 36 (43.9%) patients responded to BCAA with a slight decrease in skeletal muscle mass index from before treatment (7.40+/-1.62) to after treatment (7.30+/-1.49) (P=0.333). CONCLUSION: BCAA supplementation improved low muscle strength in patients with chronic liver disease, but did not increase muscle mass during the treatment period. PMID- 28984679 TI - Influence of laboratory-related and endoscopy-related factors on the assessment of serum pepsinogens and gastrin-17. AB - BACKGROUND AND AIM: Serum pepsinogen I (PGI) and pepsinogen II (PGII) are noninvasive parameters in the detection of atrophic gastritis. The diagnostic add on value of serum gastrin-17 (G-17) remains uncertain. The aim of this study was to assess the stability of these serum parameters over time and to evaluate the influence of clinical factors, such as upper gastrointestinal (GI) endoscopy and bowel cleansing, on serum PGI, PGII, and G-17 assessment. PATIENTS AND METHODS: A prospective study was carried out in healthy individuals and patients. For the stability analyses, the plasma and serum samples from 23 individuals were processed at different time points with and without the addition of a stabilizer. Ten patients were included to evaluate the influence of upper GI endoscopy and 18 patients to evaluate the effect of bowel cleansing before colonoscopy. RESULTS: PGI, PGII, and G-17 levels were not statistically different in the serum and plasma. PGI and PGII serum levels were stable over time. G-17 is associated with time-dependent degradation (P=0.0001). The addition of the G-17 stabilizer showed no improvement in stability. Upper GI endoscopy and bowel preparation before colonoscopy were associated with minimal variations in PGI and PGII, whereas G-17 showed patient-specific alterations. CONCLUSION: PGI and PGII serum levels are stable over time. However, G-17 stability is strongly dependent on the time of processing and storage; therefore, samples for G-17 analysis need to be processed no later than 6 h after blood collection. Upper GI endoscopy and colonoscopy preparation lead to minimal nonsignificant changes in basal PGI, PGII, and G-17 levels. PMID- 28984680 TI - Pan-tibial avascular necrosis in a 12-year-old boy: a case report. AB - We report a unique case of post-traumatic avascular necrosis of tibia in a 12 year-old boy following a Salter-Harris type II physeal injury of the proximal tibia. The diagnosis was made on the basis of classical radiological findings. The only clinical symptom was diffuse shin pain. The patient was managed conservatively. At our 2-year follow-up, there was clinical and radiological evidence of spontaneous resolution of avascular necrosis, but with sequelae. The child developed a limb-length discrepancy and genu valgum. The parents of the child refused further treatment. PMID- 28984681 TI - Functional outcome of displaced radial head fractures in children treated by elastic stable intramedullary nailing. AB - The objectives of this study were to retrospectively investigate the clinical and radiological outcomes of displaced radial head fractures in children treated by elastic stable intramedullary nailing (ESIN) and evaluate the functional outcome of these injuries using the short version of the Disabilities of the Arm, Shoulder and Hand outcome questionnaire (Quick DASH). A total of 24 patients (nine males and 15 females) fulfilled the inclusion criteria. The mean age at the time of injury was 10.7+/-2.8 years (range: 9.5-16.33 years). Before surgery, the mean angulation was 53.8 degrees +/-18.4 degrees (range: 28 degrees -82 degrees ) differentiating fractures on the basis of Judet's classification. The mean Quick DASH score was a good 4 (range: 0-15.9). Functional outcomes were similar irrespective of the severity of fracture displacement (P>0.05), presence or absence of associated fracture (P>0.05), and time immobilized (P>0.05). The Quick DASH score was better in children younger than 9 years of age (1.62) than children older than 9 years of age (4.95), but without a statistically significant difference (P=0.058). Children with displaced radial head fractures treated with ESIN showed good functional outcomes. Associated fracture injuries were not a predictive factor of functional outcome. Open reduction must be avoided as it carries an increased risk of complications. PMID- 28984682 TI - Anxiety, Depression, and Pain Symptoms: Associations With the Course of Marijuana Use and Drug Use Consequences Among Urban Primary Care Patients. AB - OBJECTIVES: This exploratory study aims to investigate whether anxiety, depression, and pain are associated with changes in marijuana use and drug use consequences among primary care patients. METHODS: In all, 331 adult primary care patients with marijuana as the only drug used were followed prospectively to investigate associations between anxiety/depression symptoms (no/minimal symptoms; anxiety or depression symptoms; symptoms of both) and pain (1-10 scale: none [0]; low [1-3]; medium [4-6]; high [7-10]) (independent variables) and substance use outcomes in regression models. These outcomes were changes (over 6 months) in primary outcomes: marijuana use days (past 30); and drug use consequences (Short Inventory of Problems-Drugs [SIP-D]); secondary outcomes-drug use risk (Alcohol, Smoking, and Substance Involvement Screening Test [ASSIST] score for drugs). RESULTS: At baseline, 67% reported no/minimal anxiety/depression symptoms, 16% anxiety or depression symptoms, 17% both; 14% reported no pain, 16% low, 23% medium, 47% high pain level. Mean (SD) number of marijuana use days was 16.4 (11.6), mean SIP-D 5.9 (9.0), mean ASSIST 12.5 (7.8); no significant association was found between anxiety/depression and marijuana use changes. Given the same baseline status for SIP-D and ASSIST, respectively, those with anxiety or depression had greater increases in SIP-D (adjusted mean difference [95% confidence interval] +3.26 [1.20; 5.32], P = 0.004) and borderline significant increases in ASSIST (+3.27 [-0.12; 6.65], P = 0.06) compared with those without anxiety or depression; those with both anxiety and depression had greater increases in ASSIST (+5.42 [2.05; 8.79], P = 0.003), but not SIP-D (+1.80 [-0.46; 4.06], P = 0.12). There was no significant association between pain and marijuana use and SIP-D changes. Given the same baseline ASSIST level, those with high pain level had greater increases in ASSIST (+4.89 [1.05; 8.72], P = 0.04) compared with those with no pain. CONCLUSION: In these exploratory analyses, anxiety, depression, and high pain level appear to be associated with increases in drug-related harm among primary care patients using marijuana. PMID- 28984683 TI - Reversine induces autophagic cell death through the AMP-activated protein kinase pathway in urothelial carcinoma cells. AB - Urothelial carcinoma is one of the most common malignancies of the urinary tract. Effective treatment of advanced urothelial carcinoma remains a clinical challenge with poor outcomes in these patients. Previous reports have shown that the expression of aurora kinase is associated with clinical stage and prognosis; hence, aurora kinases are potential targets in urothelial carcinoma therapy. Reversine, an aurora kinase inhibitor, was analyzed for its cytotoxicity in this study. Cell proliferation, flow cytometry, western blotting, and immunofluorescent assay were used to determine the effect of reversine on urothelial carcinoma cells. The results showed that reversine significantly inhibits the growth of urothelial carcinoma cell lines. Reversine induced cell cycle arrest at the G2/M phase, leading to autophagic cell death by activating the AMP-activated protein kinase pathway. Reversine induced significant cell death in urothelial carcinoma cells. Our results suggest that reversine may be a suitably small molecule for treating urothelial carcinoma in the future. PMID- 28984684 TI - Influence of the alkylating function of aldoifosfamide on the antitumor activity. AB - The present work investigates the influence of different DNA damages caused by different isophosphoramide mustards on the 3-hydroxypropanal-assisted apoptotic antitumor activity of oxazaphosphorine cytostatics using I-aldophosphamide perhydrothiazine (IAP) and mesyl-I-aldophosphamide-perhydrothiazine (SUM-IAP) for in-vitro and in-vivo experiments. IAP and SUM-IAP hydrolyze spontaneously to the corresponding I-aldophosphamide derivatives. They differ in the chemical structure of the alkylating moiety, whereas IAP has two chlorethyl groups in the SUM-IAP molecule, one chlorethyl group is substituted by a mesylethyl group. With both substances, cytotoxicity studies on P388 tumor cells in vitro and therapy experiments in mice bearing advanced growing P388 tumors were carried out. IAP was significantly more cytotoxic in-vitro than SUM-IAP, but the antitumor activity of SUM-IAP was by order of magnitude higher than the antitumor activity of IAP. The reason for these findings is discussed with respect to the enzymatic cleavage of the various I-aldophosphamide derivatives to the corresponding isophosphoramide mustards and 3-hydroxypropanal. Overall, the findings indicate that antitumor activity of ifosfamide and derivatives of ifosfamide can be improved considerably by altering the alkylating moiety of the molecule, but retaining the aldophosphamide structure. PMID- 28984686 TI - Intraobserver and Interobserver Reliability of Radiographic Analysis of Proximal Humerus Fractures in Adolescents. AB - BACKGROUND: Multiple studies have shown low intrarater and interrater agreement of radiographic classification systems for proximal humerus fractures (PHFs) in adults. There is no standardized method of measuring angulation of pediatric PHFs, nor is there consensus as to the amount of angulation and displacement that require operative fixation of adolescent PHFs. We propose a new standardized method to measure fracture angulation that is similar to the method used to measure the epiphyseal-shaft angle for slipped capital femoral epiphysis. The primary purpose of this study was to evaluate the intraobserver and interobserver reliability of our proposed method compared with a nonstandardized method. The secondary purpose was to evaluate the intrarater and interrater agreement of the Neer and Horowitz (NH), and Salter-Harris (SH) classification systems. METHODS: Seven raters evaluated 26 deidentified anteroposterior shoulder radiographs of patients 10 to 16 years of age with PHFs. Raters classified each fracture using the NH and SH systems, and used their own method to measure fracture angulation. This process was repeated 2 weeks later. During the second round, raters also measured fracture angulation using our proposed standardized method. Two weeks after the second round, raters reevaluated the radiographs using the standardized method. Intraclass correlation coefficients were calculated. RESULTS: Excellent intraobserver and interobserver agreement was achieved for the standardized method of measuring fracture angulation. All of the raters had an intrarater reliability classified as excellent (>0.80) using the standardized method. Good intrarater and excellent interrater agreement was achieved when raters used their own fracture angulation measurement method but wide confidence intervals suggested that the results were less precise. Fair to moderate intrarater and interrater reliability was seen for the NH and SH classifications. CONCLUSIONS: Our standardized method for measuring angulation in adolescent PHFs demonstrated excellent intrarater and interrater reliability. We propose that this technique may be a more precise method of measuring fracture angulation and this method should be used in future studies that evaluate indications for operative management of adolescent PHFs. LEVEL OF EVIDENCE: Level III-diagnostic. PMID- 28984687 TI - Chemical-Induced Hearing Loss in Shipyard Workers. AB - OBJECTIVE: The aim of this study was to determine the effect of lead, cadmium, arsenic, toluene, and xylene exposure on hearing compared with noise exposures alone. METHODS: Personnel at a shipyard (n = 1266) were divided into four exposure groups on the basis of concentrations: low metals/low solvents/high noise (reference group), high metals/high solvents/low noise, high metals/low solvents/high noise, and high metals/high solvents/high noise. Hearing changes occurring from the years 2004 to 2015 were analyzed. RESULTS: Hearing changes were significantly worse at 1000 Hz (P = 0.007), averaged across 2000 to 4000 Hz (P = 0.014), and averaged across 500 to 6000 Hz (P = 0.014) for the high metals/high solvent/high noise group compared with the low metals/low solvents/high noise only reference group. CONCLUSION: Simultaneous exposures classified as high for metals/solvents/noise appear to damage hearing more than exposure to noise alone. Hearing conservation programs should take into consideration combined exposures to metals, solvents, and noise, not simply exposure to noise. PMID- 28984689 TI - Functional foods and dietary supplements in 2017: food for thought. PMID- 28984690 TI - PD-1/PD-L1 and VEGF-A/VEGF-C expression in lymph node microenvironment and association with melanoma metastasis and survival. AB - Regional lymph nodes are affected frequently by melanoma metastasis. Its microenvironment may be associated with tumor progression. We investigated sentinel nodes with and without tumor and negative nodes surrounding positive nodes, looking for patterns related to tumor immune interaction and lymphovascular progression. We quantified programmed cell death protein 1 (PD 1)/programmed cell death-ligand 1, vascular endothelial growth factor (VEGF) A/VEGF-C expressions in lymph nodes of 103 patients who underwent sentinel lymph node biopsy. Two groups were studied: negative sentinel lymph nodes and positive ones. Negative lymph nodes of sequential lymphadenectomy from positive cases were also studied. Markers were assessed by immunohistochemistry. Results were related to clinical/histological outcomes. VEGF-A/VEGF-C analysis showed higher positivity in metastatic nodes and higher positivity in the surrounding negative nodes from positive cases in comparison with nonmetastatic patients. Programmed cell death-ligand 1, studied only in metastasis, presented high positivity, not associated with prognosis. PD-1 expressions were similar in the groups with a 1% cutoff and higher in the metastasis with a 5% cutoff. Higher VEGF-A expression was related to higher pathological stages. PD-1 expression in the lymph node was associated with higher survival. Other clinical and histopatological variables were not associated with marker expression patterns. VEGF-A and VEGF-C expressions in lymph nodes were associated with the presence of lymph node metastasis. PD-1 expression in the lymph node was related to higher survival rates and this should be explored in the context of adjuvant immunotherapy. PMID- 28984691 TI - Intracorneal pustular drug eruption, a novel cutaneous adverse event in anti programmed cell death-1 patients that highlights the effect of anti-programmed cell death-1 in neutrophils. AB - The introduction of anti-programmed cell death-1 (anti-PD1) monoclonal antibodies has revolutionized the treatment of various advanced malignancies. Despite its efficacy, anti-PD1 therapy is accompanied by a variety of cutaneous adverse events. A 79-year-old man developed erythematous scaly plaques and pustules of the forehead, legs and arms after four cycles of nivolumab infusions every 2 weeks. Histology showed intracorneal pustules with dermal neutrophils and eosinophils. He was treated successfully with topical corticosteroids without discontinuation of nivolumab. We report subcorneal pustular eruption as a novel cutaneous adverse event in patients on anti-PD1 therapy. Other neutrophilic eruptions (psoriasis, Sweet's syndrome, acute generalized pustulosis) have been reported in patients on anti-PD1 treatments, suggesting the neutrophil as another cell type modulated by anti-PD1 antibodies. PMID- 28984692 TI - Annular Scaly Plaque on the Left Foot. PMID- 28984693 TI - Myoepithelial-Rich and Infiltrative Giant Vascular Eccrine Spiradenoma: A Unique Presentation of a Rare Adnexal Tumor. AB - A rare variant of the eccrine spiradenoma, the giant vascular eccrine spiradenoma, has been characterized as a large circumscribed and sometimes hemorrhagic solitary tumor occurring in adults older than 50 years. Histopathologically, the lesion is comprised of distinct cell populations and cystic hemorrhagic glandular spaces. We present a 68-year-old Bengali man with a giant vascular eccrine spiradenoma and describe immunohistochemical features of this tumor. In addition, we highlight unique aspects of this case, including a rich myoepithelial component and focal pseudocapsular infiltration. PMID- 28984694 TI - Cold-Induced Dermatoses: Case Report and Review of Literature. AB - Cold panniculitis and perniosis are the most common cold-induced dermatologic disorders and are clinically characterized by indurated and erythematous nodules and plaques that develop at sites exposed to excessive cold and wet conditions. Cold panniculitis is most commonly seen in infants, but adult cases involving the thighs of equestrians are well known and have come to be known as equestrian cold panniculitis or equestrian perniosis. Recently, similar cases have been described in nonequestrian settings with the prolonged use of ice-packs or other cold therapy devices. We describe the case of 51-year-old female patient who underwent recent arthroscopic shoulder surgery for repair of a rotator cuff tear and presented to the dermatology clinic for painful and erythematous nodules on her arm. A punch biopsy demonstrated a superficial and deep perivascular and periappendageal lymphocytic infiltrate with some spillover into the superficial subcutaneous adipose tissue. Focal vacuolar changes along the basal layer of the epidermis with a few dyskeratotic keratinocytes were present. A mild increase in interstitial mucin was seen, but no significant papillary dermal edema. On clinical questioning she admitted to sustained use of icepacks on the injured shoulder postoperatively for up to 18 hours a day. Based on clinical and histopathologic features the diagnosis of ice-pack dermatosis was made. A review of cold-induced dermatoses is considered with a focus on the main histologic differential diagnoses. PMID- 28984695 TI - Primary Cutaneous CD8+ T-cell Lymphoma, an Indolent and Locally Aggressive Form Mimicking Paronychia. AB - CD8 T-cell lymphomas comprise a wide spectrum of lymphomas, many which have yet to be formally classified. We present a case of a 43-year-old woman with an enlarging tumor distal to the distal interphalangeal joint of the fourth finger, compressing the underlying nail matrix. Magnetic resonance imaging showed bony involvement of the underlying distal phalanx. Histology showed a dense epidermotropic and pandermal infiltrate composed of medium-sized, uniformly pleomorphic lymphocytes with cleaved nuclei, which raised the possibility of primary cutaneous CD8 aggressive epidermotropic cytotoxic T-cell lymphoma. However, the patient's clinical photograph was inconsistent with this diagnosis. Other diagnoses, such as primary cutaneous acral CD8 T-cell lymphoma-a provisional entity, were also considered but did not capture all the features of this patient's lymphoma. We propose to classify this case as a primary cutaneous CD8 T-cell lymphoma, an indolent and locally aggressive form. PMID- 28984696 TI - Heterotopic Cutaneous Meningioma: An Unusual Presentation Occurring in a Patient With a Remote History of Intracranial Meningioma. AB - Meningioma is a neoplasm of the meninges, which usually occurs in intracranial sites. Extracranial meningioma has been frequently reported in the sinonasal tract and skull bone, often as extension of intracranial meningiomas. Isolated heterotopic meningioma without contiguous intracranial lesion is extremely rare. A 56-year-old woman presented in December 2015 with 2 firm subcutaneous scalp masses; one in the left lateral (temporal) and the other in the left superior (parietal) region. The clinical impression was that of lipoma. Pathologic examination revealed an ill-defined proliferation of uniform meningothelial cells in a fibroblastic stroma interspersed within adipose tissue. The excised lesions had similar histologic features. Immunohistochemical stains were performed and the tumor cells were positive for epithelial membrane antigen and negative for S 100. A diagnosis of extracranial meningioma, WHO grade I was made. The patient's medical history was significant for intracranial meningioma of the frontal lobe in October 2007, which was diagnosed as atypical meningioma, WHO grade II. Comparison of the scalp masses to her previous meningioma revealed a distinctly different morphologic pattern. In light of the 8-year interval between the scalp and intracranial meningioma and the difference in histologic grades, it is unlikely that her most recent tumors represent a recurrence or metastasis of the intracranial tumor. PMID- 28984697 TI - Mixed Lichenoid and Follicular T- and B-Cell Lymphoid Reaction to Red Tattoos With Monoclonal T Cells. AB - Pseudolymphomatous reactions have been described to occur in tattoos. Most cases have exhibited T-cell predominance and polyclonal T-cell receptor gene rearrangements. One case with monoclonal IgH gene rearrangements progressed into B-cell lymphoma. Lichenoid infiltrates are commonly described but lymphoid follicles much less frequently. We report a case with mixed lichenoid and follicular T- and B-cell reaction to red tattoos. The histopathology and the immunohistochemical studies were constant with a mixed T- and B-cell pseudolymphoma, the IgH gene rearrangement study was polyclonal, but the T-cell receptor gene rearrangement study was monoclonal. The patient who responded to intralesional corticosteroid injections remains under close scrutiny. PMID- 28984698 TI - Relative Importance Assigned to Health Care Rationing Principles at the Bedside: Evidence From a Portuguese and Bulgarian Survey. AB - Activity was undertaken to develop a Prioritization Scoring Index for Portugal and Bulgaria that weights the importance given to ethical rationing principles that should guide decisions at the bedside. Data from two random samples of 355 Portuguese and 298 Bulgarian members of the public were collected from an online questionnaire. Questions asked about the level of importance given to specific issues related to patient's prioritization criteria. Responses were analyzed quantitatively with the SPSS. In the process of selecting the patient to treat, Portuguese and Bulgarian respondents seem unanimous in giving greater importance to (i) the treatment outcomes, (ii) the severity of illness, (iii) children, and (iv) patients' fragility. In general, Portuguese and Bulgarian respondents allocate more than 50% of the prioritization weight to equity considerations, approximately 35% to efficiency considerations, and 5% to lottery selection. Even so, Bulgarian respondents rate highly the equity and less the efficiency consideration than Portuguese respondents. Although the pursuit of efficiency seems to be valued by respondents, their major concern seems to be with the reduction of inequalities in health. PMID- 28984699 TI - Emerging techniques in assessment and treatment of muscle tension dysphonia. AB - PURPOSE OF REVIEW: The purpose of this review is to summarize current evidence regarding treatment for muscle tension dysphonia (MTD) and to present recent advances in evaluation and management. RECENT FINDINGS: It is generally accepted that voice therapy for MTD is effective, but current systematic reviews report limited evaluation specific to MTD patients with moderate evidence, at best, available to support voice therapy techniques. Individual studies are difficult to compare because of heterogeneity. Considerable work is underway to identify most important metrics to include in assessment, and to advance and define direct voice therapy approaches. SUMMARY: Further standardization of assessment and treatment protocols for MTD will improve future research. Novel therapeutic techniques are under investigation. In small studies, these have found value in improving voice outcomes and measures compared with pretreatment values but have not met success greater than existing therapeutic methods. PMID- 28984701 TI - HIV-related cardiovascular disease: closing the gap in mortality. AB - : This series of review articles outlines the complex cause of HIV-related cardiovascular diseases (CVDs) particularly the interactions of viral factors, complications of antiviral therapy such as metabolic derangement, and chronic systemic inflammation. These factors, directly stemming from chronic HIV infection, are important in the pathogenesis of HIV-related CVD. Addressing each issue has likely underpinned the improved morbidity and increased life expectancy enjoyed by patients in the modern era of HIV management. The global management of HIV-related CVD may, however, be simpler than previously imagined, as the disease likely follows a pathway shared by multiple systemic diseases. Other chronic systemic diseases, including diabetes, rheumatoid arthritis, and autoimmune disease, share numerous pathophysiological mechanisms with HIV and provoke similar cardiac complications. CVD risk management in patients living with HIV (PLHIV) may be optimized by drawing upon existing knowledge of chronic systemic diseases which may open up new concepts in treatment and address the current shortfalls in cardiovascular management of PLHIV. PMID- 28984702 TI - Current assessment of heart rate variability and QTc interval length in HIV/AIDS. AB - PURPOSE OF REVIEW: The increasing prevalence of cardiovascular disease comorbidity in persons infected with the HIV has become a global concern. The electrocardiogram (ECG) is increasingly being utilized to provide clinically relevant information regarding cardiac arrhythmias and cardio-autonomic dysfunction. The purpose of this review is to summarize the latest research comparing QT and R-to-R interval length as a function of HIV+ status or antiretroviral therapy (ART) regimen. RECENT FINDINGS: Prolongation of the corrected QTc interval may be acquired in HIV+ ART-naive individuals, exacerbated by various classes of ART drugs, and is generally predictive of lethal cardiac arrhythmias, with effects observed from childhood to adulthood. Recent literature also suggests the trend of lower heart rate variability in HIV is indicative of cardiorespiratory and inflammatory-immune dysfunction. SUMMARY: These emergent studies support the clinical relevance of the ECG across the age and HIV disease spectrum. Furthermore, the reported findings have implications for the management of cardiovascular and chronic inflammatory disease comorbidity in persons living with HIV. PMID- 28984703 TI - Pathophysiology of ischaemic heart disease. AB - PURPOSE OF REVIEW: To summarize recent findings in the pathogenesis of ischemic heart disease (IHD) in people living with HIV (PLWH). RECENT FINDINGS: PLWH have an elevated risk of IHD. Although incidence is declining, this condition still represents a major cause of non-AIDS-related mortality. The cause is likely multifactorial: traditional risk factors play an important role and IHD risk might be reduced with greater emphasis on primary prevention. The contribution of specific antiretroviral agents to IHD risk is changing as antiretroviral coverage increases globally and as safer agents have replaced drugs with well-described metabolic toxicities. The beneficial impact of virological suppression on antiretroviral therapy (ART) in reducing IHD is particularly evident in participants with advanced HIV infection and high baseline cardiovascular risk. The association between current abacavir use and myocardial infarction is still unexplained and indicates that mechanisms other than metabolic alterations may underlie IHD in PLWH. Consequently, the contributions of inflammation, subclinical atherosclerosis and endothelial dysfunction are receiving greater attention. SUMMARY: Modern ART coupled with intensified efforts towards primary prevention is the cornerstone of IHD risk management in PLWH. The role of chronic inflammation and its optimal management need to be defined. PMID- 28984704 TI - The promises of immunotherapy in gliomas. AB - PURPOSE OF REVIEW: Also owing to the limited efficacy of targeted therapies, there has been a renewed interest in targeting gliomas with immunotherapy. But despite considerable efforts using sophisticated approaches, proof of efficacy beyond case studies is still lacking. The purpose of this review is to summarize and discuss current immunotherapeutic approaches and efforts to understand mechanisms of response and resistance. RECENT FINDINGS: The recent failure of large randomized clinical trials using targeted vaccines and checkpoint inhibitors to improve clinical outcome have underlined the grand challenges in this therapeutic arena and illustrated the necessity to understand the biology of immunotherapeutic interventions before conducting large randomized studies. However, these failures should not distract us from continuing to optimize immunotherapeutic concepts. The recent developments in transgenic T cell technologies and personalized vaccines but also rational combinatorial approaches offer tremendous opportunities and should be exploited carefully in early scientifically driven clinical trials. SUMMARY: A profound understanding of the cellular and molecular mechanisms of response and resistance to immunotherapy to be gained from these thoroughly designed clinical trials will be essential to carve out successful strategies in selected patient populations. PMID- 28984706 TI - Engaging Community Health Workers in the Effort to Prevent Sudden Unexpected Death and Death From Chronic Illness. PMID- 28984705 TI - The crashing patient: hemodynamic collapse. AB - PURPOSE OF REVIEW: Rapid restoration of tissue perfusion and oxygenation are the main goals in the resuscitation of a patient with circulatory collapse. This review will focus on providing an evidence based framework of the technological and conceptual advances in the evaluation and management of the patient with cardiovascular collapse. RECENT FINDINGS: The initial approach to the patient in cardiovascular collapse continues to be based on the Ventilate-Infuse-Pump rule. Point of care ultrasound is the preferred modality for the initial evaluation of undifferentiated shock, providing information to narrow the differential diagnosis, to assess fluid responsiveness and to evaluate the response to therapy. After the initial phase of resuscitative fluid administration, which focuses on re-establishing a mean arterial pressure to 65 mmHg, the use of dynamic parameters to assess preload responsiveness such as the passive leg raise test, stroke volume variation, pulse pressure variation and collapsibility of the inferior vena cava in mechanically ventilated patients is recommended. SUMMARY: The crashing patient remains a clinical challenge. Using an integrated approach with bedside ultrasound, dynamic parameters for the evaluation of fluid responsiveness and surrogates of evaluation of tissue perfusion have made the assessment of the patient in shock faster, safer and more physiologic. PMID- 28984709 TI - Measurement of Optic Disc Cup Surface Depth Using Cirrus HD-OCT. AB - PURPOSE: To introduce the measurement method of optic disc cup surface depth using spectral-domain optical coherence tomography (SD-OCT) and then evaluate the rates of cup surface depression at 3 different stages of glaucoma. MATERIALS AND METHODS: We retrospectively identified 52 eyes with preperimetric glaucoma, 56 with mild-or-moderate glaucoma and 50 with severe glaucoma and followed them for at least 48 months. Eyes were imaged using SD-OCT (Cirrus HD-OCT) at 12-month intervals. The mean cup surface depth was calculated using the following formula: Cup volume/(disc area*average cup-to-disc ratio)-200 MUm. RESULTS: The rates of mean cup surface depression (MUm/y) were significantly greater in mild-or moderate glaucoma (-7.96+/-1.03) than in preperimetric (-3.11+/-0.61) and severe glaucoma (-0.70+/-0.12; all P<0.001). The percentile rates of mean cup surface depression (%/y) were significantly greater than those of average of retinal nerve fiber layer (RNFL) thinning (%/y) in preperimetric glaucoma (-1.64+/-0.12 vs. -1.11+/-0.07; P<0.001) and mild-or-moderate glaucoma (-4.20+/-0.33 vs. 3.14+/-0.19; P<0.001); and conversely, in severe glaucoma, mean cup surface depth changed slower than did average RNFL thickness (-0.64+/-0.06 vs. -0.75+/-0.08%/y; P<0.001). CONCLUSIONS: In early-to-moderate glaucoma, the cup surface depth changed faster than did the RNFL thickness. These results signify the possibility that SD-OCT-based estimation of cup surface depth might be useful for monitoring of glaucoma development and progression. PMID- 28984707 TI - Incident Cardiovascular Risk Factors Among Men and Women Veterans After Return From Deployment. AB - BACKGROUND: Stressors associated with military service and reintegration may impact psychologic well-being and behaviors that result in increased incidence rates for cardiovascular (CV) risk factors. OBJECTIVE: Using electronic health record data from the Veterans Health Administration we sought to measure the incidence of newly diagnosed CV risk factors and how these incident risks were moderated by race and mental health conditions. DESIGN: A cohort study including Veterans whose end of last deployment was between October 1, 2001 and July 31, 2014. SUBJECTS: A total of 267,305 Operations Iraqi Freedom, Enduring Freedom, and New Dawn Veterans were present. MAIN OUTCOME MEASURES: Incident risk factors (hypertension, obesity, dyslipidemia, diabetes, or coronary artery disease), identified through new International Classification of Diseases, 9th Revision, Clinical Modification diagnostic codes or measurement recordings at primary care visits. RESULTS: The rate of developing at least 1 risk factor or coronary artery disease was 240 and 151 per 1000 person-years in men and women, respectively. Except for obesity, women were significantly less likely to develop any other CV risk factor compared with men (Crude hazard ratios ranging from 0.44 to 0.82). The impact of sex on hypertension (P<0.001) and obesity (P<0.001) was modified by race and the impact of sex on the combined event of any risk factor (P=0.007) and obesity (P<0.001) was modified by depression. CONCLUSIONS: Compared with men, women Veterans were more likely to become obese after return from deployment, but less likely to develop any other risk . For black women, the protective effect of female sex on the combined event (any risk factor), and hypertension was lessened compared with white women. The increased risk of obesity for women was greater in black women, and those with depression. PMID- 28984710 TI - Risk Factors Associated With Glaucomatous Progression in Pseudoexfoliation Patients. AB - PURPOSE: To investigate risk factors associated with glaucomatous progression in pseudoexfoliation glaucoma (PXG) patients. PATIENTS AND METHODS: A retrospective observational study with a total of 48 PXG patients and age, sex, and visual field (VF) test mean deviation-matched 48 primary open-angle glaucoma (POAG) patients recruited from 3 university-based hospitals. Glaucomatous progression was defined by 2 criteria, either optic disc/retinal nerve fiber layer photographic assessment or serial VF data. Univariate and multivariate Cox proportional hazard models were used to detect associations between risk factors and progression in each subgroup and shared frailty model were used in total participants. RESULTS: In total participants, PXG diagnosis [hazard ratio (HR), 7.245; P=0.050], a higher baseline intraocular pressure (IOP) (HR, 1.221; P=0.025) and a greater number of glaucoma medications (HR, 3.537; P=0.016) were significant factors for glaucoma progression. In the PXG group, a higher baseline IOP (HR, 1.131; P<0.001), a lower IOP reduction (HR, 0.966; P=0.027), a greater number of glaucoma medications (HR, 2.413; P=0.004), and worse baseline VF mean deviation (HR, 0.875; P=0.004) were significant factors, whereas the number of glaucoma medications (HR, 3.493; P=0.019) and disc hemorrhage (HR, 3.953; P=0.043) showed association in the POAG group. CONCLUSIONS: Factors associated with progression differed between PXG and POAG groups. Higher baseline IOP and requirement for a greater number of glaucoma medications were related with PXG progression. PMID- 28984712 TI - Acute Angle Closure Secondary to Tubercular Choroidal Granuloma. AB - Acute angle closure is usually thought to be secondary to pupillary block, which is relieved by laser iridotomy. Anterior rotation of the ciliary body at the scleral spur following development of an inflammatory ciliochoroidal detachment may result in a presentation of acute angle closure. It is imperative to recognize this condition correctly, because the management is with cycloplegics and anti-inflammatory drugs, which is diametrically opposite to the treatment of primary angle closure. More importantly, it has been reported as a consequence of serious systemic disease such as HIV infection and Vogt Koyanagi Harada (VKH) syndrome. We report a patient who presented to the medical emergency with headache and vomiting and was subsequently found to have acute angle closure in 1 eye secondary to a tubercular choroidal granuloma. This presentation of ocular tuberculosis has not been reported previously. PMID- 28984711 TI - Genomic Organization of TBK1 Copy Number Variations in Glaucoma Patients. AB - BACKGROUND: Approximately 1% of normal tension glaucoma (NTG) cases are caused by TANK-binding kinase 1 (TBK1) gene duplications and triplications. However, the precise borders and orientation of these TBK1 gene copy number variations (CNVs) on chromosome 12 are unknown. METHODS: We determined the exact borders of TBK1 CNVs and the orientation of duplicated or triplicated DNA segments in 5 NTG patients with different TBK1 mutations using whole-genome sequencing. RESULTS: Tandemly duplicated chromosome segments spanning the TBK1 gene were detected in 4 NTG patients, each with unique borders. Four of 5 CNVs had borders located within interspersed repetitive DNA sequences (Alu and long interspersed nuclear element L1 elements), suggesting that mismatched homologous recombinations likely generated these CNVs. A fifth NTG patient had a complex rearrangement including triplication of a chromosome segment spanning the TBK1 gene. CONCLUSIONS: No specific mutation hotspots for TBK1 CNVs were detected, however, interspersed repetitive sequences (ie, Alu elements) were identified at the borders of TBK1 CNVs, which suggest that mismatch of these elements during meiosis may be the mechanism that generated TBK1 gene dosage mutations. PMID- 28984713 TI - Do Intraocular Pressure Measurements Under Anesthesia Reflect the Awake Condition? PMID- 28984714 TI - A Case of Idiopathic Bilateral Profound Hypotony. PMID- 28984715 TI - Suprachoroidal Bleeding After XEN Gel Implantation. AB - PURPOSE: To report for the first time a clinical case of suprachoroidal bleeding after XEN45 gel implantation. OBSERVATIONS: A 84-year old female patient with pseudoexfoliation glaucoma with intraocular pressure (IOP) (20 mm Hg) above target despite maximal IOP-lowering therapy was scheduled for XEN45 gel implantation. The XEN45 gel implantation went without complications and was properly placed in the anterior chamber and beneath the conjunctiva. On the first postoperative day, the patient presented with an IOP of 4 mm Hg, a functioning bleb and a deep anterior chamber. On the second day she developed suprachoroidal bleeding. A wait and see strategy was followed and the patient monitored steadily. The bleeding resolved spontaneously after 6 weeks. CONCLUSIONS AND IMPORTANCE: Minimally invasive glaucoma surgery is developed to provide a safer and less-invasive option to reduce IOP in glaucoma patients compared with trabeculectomy. Although the concept of the XEN45 gel stent seems to be a favorable to reach IOP-lowering results similar to those of trabeculectomy, complications may be similar, too. We have to keep this in mind when informing patients about surgical options. PMID- 28984716 TI - Author Response, "Do Intraocular Pressure Measurements Under Anesthesia Reflect the Awake Condition?" PMID- 28984717 TI - Idiopathic Bilateral Profound Hypotony in an Unknown Progressive Neurodegenerative Disorder. PMID- 28984718 TI - Endoscopic Treatment of the Zenker Diverticulum With Flexible Endoscopic Myotomy: A Single Tertiary Center Experience. AB - INTRODUCTION: The Zenker diverticulum (ZD) is the most common type of esophageal diverticula. Management of ZD has different options; however, there is a recent increase in treatment with flexible endoscopic myotomy (FEM). In our study, we aimed to investigate the efficacy and safety of FEM among patients with ZD. MATERIALS AND METHODS: The data of patients who underwent FEM for ZD in our clinic between January 2008 and May 2016 were retrospectively analyzed. Myotomy was performed with a needle-knife sphincterotome by using pulse-cut or forced coagulation electrocautery mode. Myotomy was performed on the common wall of the diverticulum up to 0.5 to 1 cm of the distal end. A handmade diverticuloscope, which was modified from an overtube, was used in most of the patients to focus more carefully on the septum. Dysphagia scores of the patients before and after the procedure were compared and complications were evaluated. RESULTS: A total of 17 patients were enrolled in the study. The mean age was 65.3 years, and mean diverticular diameter was 3.2 cm. The most common symptoms were dysphagia and regurgitation. The mean in-hospital stay was 5 days. The dysphagia score was significantly decreased after FEM among the patients (0.17+/-0.39 vs. 2+/-0.79; P=0.0001). Complications were observed in 3 patients (17.6%); however, there was no procedure-related mortality. DISCUSSION: FEM is an efficient and safe procedure as a treatment modality for ZD. However, lack of a standard algorithm is a remarkable disadvantage. PMID- 28984719 TI - Laparoscopic Appendectomy in Pregnancy With Acute Appendicitis: Single Center Experience With World Review. AB - OBJECTIVES: This clinical study is aiming to discuss the therapeutic benefit of laparoscopic appendectomy (LA) by comparing with conventional open appendectomy (OA) in pregnancy. MATERIALS AND METHODS: The clinical data of 26 pregnant women who underwent appendectomy from 2012 to 2016 was retrospectively analyzed. The variables analyzed included baseline information, operation characteristics, maternal complications, and infant health outcomes. The patients were divided in 2 LA and OA groups according to the surgical approach and their clinical characteristics were compared. RESULTS: Of reported 26 patients, 7 underwent LA whereas the remaining 19 patients underwent OA. The median age of the patients was 28 years (range, 19 to 39 y). The median gestational period was 21.5 weeks (range, 5 to 33 wk). The postoperative pathology showed complicated appendicitis 7 cases. The result showed significantly shorter operation time (42.14+/-8.63 vs. 65.21+/-26.58 min, P=0.003), hospital stay (4.14+/-1.77 vs. 6.47+/-2.72 d, P=0.021), and earlier recovery of gastrointestinal function in the LA group compared with OA group. There were no maternal and fetal deaths occurred in perioperative period in both groups. CONCLUSIONS: LA has not increased morbidity and mortality but displayed shorter hospital stay, operation time and recovery of gastrointestinal function to OA as well as good cosmetic results. Therefore, LA in patients with pregnancy can be considered as preferred approach in sophisticated hands without increased risks. PMID- 28984720 TI - Prevention of bladder cancer incidence and recurrence: tobacco use. AB - PURPOSE OF REVIEW: To summarize the current knowledge about smoking carcinogenesis in bladder cancer (BCa), individual susceptibility and impact of smoking on incidence and outcomes of nonmuscle invasive BCa (NMIBC) and muscle invasive BCa (MIBC). To assess the impact of smoking cessation on oncological outcomes. RECENT FINDINGS: Smoking pattern, intensity, and duration are responsible for an increased risk of developing BCa and for worse tumor features at presentation. Tobacco consumption is associated with a higher risk of recurrence in NMIBC and with an impaired intravesical therapy efficacy. To date, the impact of smoking on oncological outcomes after radical surgery remains unclear. SUMMARY: Smoking cessation decreases the risk of BCa and may also allow benefits on treatment outcomes. Nonetheless, the magnitude of the effect remains unclear and prospective series with the specific aim of weighing smoking cessation on outcomes are needed. Because even a 5-min counseling in the urology setting may be sufficient to significantly enhance smoking cessation rates, adequate knowledge of links between tobacco and BCa, from its molecular pathophysiology and its harms to benefits of cessation is paramount for urologists and for everyday clinical practice. PMID- 28984721 TI - Would Parents Consent to a Comparative Effectiveness Trial of Oral Doxycycline Versus Intravenous Ceftriaxone for the Treatment of Children with Lyme Meningitis? AB - Children with Lyme meningitis are often treated with intravenous ceftriaxone, although oral doxycycline may be effective. Parents were surveyed after observing a video describing a hypothetical Lyme meningitis treatment trial. Eighty-four of 102 (82%) would consent to their child participating. Parents would accept 2 additional days of symptoms (noninferiority margin) with doxycycline even if ceftriaxone hastened symptom resolution. PMID- 28984722 TI - Safety and Efficacy of Micafungin in Extremely Low Birth Weight Infants. AB - Little is known about the side effects of micafungin in extremely low birth weight infants. In a retrospective single-center study, 19 extremely low birth weight infants were analyzed for micafungin efficacy and safety. At a mean+/ standard deviation daily dosage of 7.5 +/- 2.0 mg/kg, no clinically relevant side effects were observed. A significant increase of liver enzymes was reversible after treatment. PMID- 28984724 TI - Neuro-ophthalmic manifestations of cerebrovascular accidents. AB - PURPOSE OF REVIEW: Ocular functions can be affected in almost any type of cerebrovascular accident (CVA) creating a burden on the patient and family and limiting functionality. The present review summarizes the different ocular outcomes after stroke, divided into three categories: vision, ocular motility, and visual perception. We also discuss interventions that have been proposed to help restore vision and perception after CVA. RECENT FINDINGS: Interventions that might help expand or compensate for visual field loss and visuospatial neglect include explorative saccade training, prisms, visual restoration therapy (VRT), and transcranial direct current stimulation (tDCS). VRT makes use of neuroplasticity, which has shown efficacy in animal models but remains controversial in human studies. SUMMARY: CVAs can lead to decreased visual acuity, visual field loss, ocular motility abnormalities, and visuospatial perception deficits. Although ocular motility problems can be corrected with surgery, vision, and perception deficits are more difficult to overcome. Interventions to restore or compensate for visual field deficits are controversial despite theoretical underpinnings, animal model evidence, and case reports of their efficacies. PMID- 28984725 TI - Ganglion cell layer complex measurements in compressive optic neuropathy. AB - PURPOSE OF REVIEW: Neuroophthalmologists and neurosurgeons are often asked by their patients what their visual prognosis will be after decompression of an optic chiasm lesion. Previous methods have been studied but have not provided consistent guidance. However, a recent algorithm which allows for retinal ganglion cell analysis from optical coherence tomography (OCT) may be more helpful. RECENT FINDINGS: Recent studies have shown that ganglion cell layer complex (GCC) measurements from OCT strongly correlate with the visual field loss associated with compressive optic neuropathies. For example, GCC measurements show corresponding binasal thinning with bitemporal hemianopia. Some investigators have also shown that more preserved GCC thickness is preoperatively associated with better postsurgical outcome. Interestingly, some patients experience almost complete recovery of visual fields despite considerable GCC thinning, and others may have GCC loss before they develop demonstrable visual field defects. SUMMARY: GCC measurements on OCT strongly correlate with visual field defects from optic chiasm compressive lesions and may help with regard to prognosis following treatment. However, considerable visual recovery is possible despite persistent GCC loss. PMID- 28984726 TI - Ophthalmic manifestations of bartonella infection. AB - PURPOSE OF REVIEW: The eye is commonly affected in disseminated cat scratch disease (CSD) caused by Bartonella species. This article reviews recently published data on epidemiology of CSD, clinical features of ocular involvement, diagnosis and treatment. RECENT FINDINGS: The annual incidence of CSD has been estimated as 4.7 per 100 000 in the United States. It occurs predominantly in the southern states, with a peak in January, and disproportionately affects children. Retinal infiltrates, neuroretinitis and branch retinal artery occlusions have been reported as common manifestations of ocular bartonellosis in recent series. The use of different antigens for serodiagnosis and new real-time PCR assays for molecular diagnosis have been described. Despite lack of a standard treatment, good visual outcomes were generally reported in patients with ocular bartonellosis. SUMMARY: Bartonella infections continue to be a burden worldwide and epidemiologic features may guide preventive measures in high-risk regions and populations. An increased awareness of diverse posterior segment manifestations will lead to an early diagnosis of ocular bartonellosis. Laboratory diagnostic methods continue to evolve and may be applied to the investigation of ocular fluids for a definitive diagnosis of ocular bartonellosis. Well designed clinical trials are required to establish the optimum treatment of especially sight threatening manifestations. PMID- 28984727 TI - Sickle cell disease and the eye. AB - PURPOSE OF REVIEW: To review recent literature pertaining to sickle cell retinopathy (SCR) and, in particular, sickle cell maculopathy. RECENT FINDINGS: Several recent studies suggest that macular perfusion abnormalities seen in patients with sickle cell disease of various genotypes may affect both the superficial and deep capillary plexi, with a predilection for the deep capillary plexus. Further, these changes may be associated with areas of macular thinning, as well as with peripheral retinal ischemia, even in individuals without visual symptoms, contrary to what has previously been described in both diabetic retinopathy and retinal vein occlusion. Several cases also suggest that paracentral acute middle maculopathy may be the pathophysiologic mechanism by which microvascular occlusion leads to macular thinning. SUMMARY: Sickle cell disease can manifest in a number of ways within the orbit as well as intraocularly because of its nonspecific vasoocclusive episodes. However, SCR is the most common ophthalmic manifestation of this disease. Historically, SCR has been considered a peripheral retinopathy, but the development and use of spectral domain optical coherence tomography and optical coherence tomography angiography suggest that significant macular vascular changes occur early in this disease, even in asymptomatic individuals. PMID- 28984728 TI - Incidence of Wrong-Site Surgery List Errors for a 2-Year Period in a Single National Health Service Board. AB - INTRODUCTION: Wrong-site/side surgical "never events" continue to cause considerable harm to patients, healthcare professionals, and organizations within the United Kingdom. Incidence has remained static despite the mandatory introduction of surgical checklists. Operating theater list errors have been identified as a regular contributor to these never events. The aims of the study were to identify and to learn from the incidence of wrong-site/side list errors in a single National Health Service board. METHODS: The study was conducted in a single National Health Service board serving a population of approximately 300,000. All theater teams systematically recorded errors identified at the morning theater brief or checklist pause as part of a board-wide quality improvement project. Data were reviewed for a 2-year period from May 2013 to April 2015, and all episodes of wrong-site/side list errors were identified for analysis. RESULTS: No episodes of wrong-site/side surgery were recorded for the study period. A total of 86 wrong-site/side list errors were identified in 29,480 cases (0.29%). There was considerable variation in incidence between surgical specialties with ophthalmology recording the largest proportion of errors per number of surgical cases performed (1 in 87 cases) and gynecology recording the smallest proportion (1 in 2671 cases). The commonest errors to occur were "wrong side" list errors (62/86, 72.1%). DISCUSSION: This is the first study to identify incidence of wrong-site/site list errors in the United Kingdom. Reducing list errors should form part of a wider risk reduction strategy to reduce wrong site/side never events. Human factors barrier management analysis may help identify the most effective checks and controls to reduce list errors incidence, whereas resilience engineering approaches should help develop understanding of how to best capture and neutralize errors.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. PMID- 28984729 TI - Simulation-Based Education Enhances Patient Safety Behaviors During Central Venous Catheter Placement. AB - OBJECTIVE: We describe the effect of simulation-based education on residents' adherence to protocols for and performance of central venous access. METHODS: Internal medicine and emergency medicine residents underwent a central venous access course that included a lecture, video presentation, readings, and simulation demonstrations presented by faculty. Baseline data were collected before the course was initiated. After a skills session where they rehearsed their ultrasound-guided central venous access skills, residents were evaluated using a procedural checklist and written knowledge exam. Residents also completed questionnaires regarding confidence in performing ultrasound-guided central venous access and opinions about the training course. RESULTS: Residents demonstrated significant improvement on the written knowledge exam (P < 0.0001) and Standard Protocol Checklist (P < 0.0001) after the training course. Training improved a number of patient safety elements, including adherence to sterile technique, transparent dressing, discarding sharps, and ordering postprocedure x rays. However, a number of residents failed to wash their hands, prepare with chlorhexidine, drape the patient using a sterile technique, anesthetize the site, and perform a preprocedure time-out. Significant improvement in procedural skills was also noted for reduction in skin-to-vein time (P < 0.003) as well as a reduction in number of residents who punctured the carotid artery (P < 0.02). CONCLUSIONS: Simulation-based education significantly improved residents' knowledge and procedural skills along with their confidence. Adherence to the protocol also improved. This study illustrates that simulation-based education can improve patient safety through training and protocols. PMID- 28984730 TI - Intradevice misalignment predicts residual leak in patients undergoing left atrial appendage closure. AB - AIMS: Postdeployment mutual orientation between the disk and the lobe in patients undergoing left atrial appendage closure with Amplatzer cardiac plug/Amulet device might impact on the risk of residual leak during follow-up. Thus, we evaluated in an exploratory, pilot study whether the degree of intradevice misalignment, measured by cardiac computed tomography (CT), discriminates the occurrence of peridevice leak in those patients. METHODS: All patients (N = 15) undergoing percutaneous left atrial appendage closure with those specific devices between April 2013 and January 2015 were prospectively included. All patients received follow-up evaluation by cardiac CT at 6 months after the intervention to calculate the angle of misalignment within the device and to detect presence of residual peridevice leak. RESULTS: The angle of misalignment between the disk and the lobe of the device significantly discriminated between patients with and without peridevice leak (area under the curve 0.96, 95% confidence interval 0.88 1.0; P = 0.003), with an angle more than 20 degrees being associated with nine fold higher risk of residual leak. This angle of intradevice misalignment calculated by cardiac CT was significantly correlated with that measured by two dimensional transesophageal echocardiography or X-rays in the cath lab after the device deployment (r = 0.943 and r = 0.938, respectively). CONCLUSION: A marked intradevice misalignment after Amplatzer cardiac plug/Amulet device implantation significantly predicts the occurrence of postprocedural leak in patients with atrial fibrillation; if confirmed by larger studies, these findings may impact on practice patterns. PMID- 28984731 TI - Bariatric surgery, hypertension, and epicardial adipose tissue. PMID- 28984732 TI - The clinical performance of dabigatran in the Italian real-life experience. PMID- 28984734 TI - A Comparison of Back Pain Functional Scale With Roland Morris Disability Questionnaire, Oswestry Disability Index, and Short Form 36-Health Survey. AB - STUDY DESIGN: A comparison study of Back Pain Functional Scale (BPFS) with Roland Morris Questionnaire (RMQ), Oswestry Disability Index (ODI), and Short Form 36 Health Survey (SF-36). OBJECTIVE: The aim of this study is to investigate the correlation of BPFS with RMQ, ODI, and SF-36. SUMMARY OF BACKGROUND DATA: The primary goal in the treatment of patients with low back pain is to improve the patients' levels of activities and participation. Many questionnaires focusing on function have been developed in patients with low back pain. BPFS is one of these questionnaires. No studies have investigated the correlation of BPFS with ODI and SF-36. METHODS: This study was conducted with 120 patients receiving outpatient and inpatient treatment in physiotherapy and rehabilitation units of a state hospital. BPFS, RMQ, ODI, and SF-36 questionnaires were used to assess the disability in low back pain. Spearman and Pearson Correlation were used to compare the data obtained in the study. RESULTS: There was a good correlation among the 5 functional outcome measures (correlation r = -0.693 for BPFS/RMQ, r = -0.794 for BPFS/ODI, r = 0.697 for BPFS/SF-36 Physical function and r = 0.540 for BPFS/SF-36 Pain). CONCLUSION: BPFS demonstrated good correlation with RMQ, ODI, SF-36 physical function, and SF-36 pain. LEVEL OF EVIDENCE: 2. PMID- 28984735 TI - Variability in Assessing Spinopelvic Parameters with Lumbosacral Transitional Vertebrae: Inter- and Intra-observer Reliability among Spine Surgeons. AB - STUDY DESIGN: Prospectively-collected survey study OBJECTIVE.: To determine the consistency with which spino-pelvic parameters (SPP) are determined in patients with lumbosacral transitional vertebrae (LSTV). SUMMARY OF BACKGROUND DATA: The incidence of LSTV in the general population is as high as 35.6%. The often fixed nature of LSTV relative to the pelvis, but lumbar-type appearance, may lead to differential use of the S1 endplate when performing SPP assessment. This could have significant impact on SPP derived from these landmarks, resulting in considerable variation in surgical planning and decision making. METHODS: 20 patients demonstrating LSTV on standing lateral 36-in spinal radiographs were randomly arranged and independently analyzed by 16 experienced spine surgeons using the same computer software. Pelvic incidence (PI), pelvic tilt (PT), lumbar lordosis (LL), and T1 pelvic angle (TPA) were captured. Two weeks after the first assessment, surgeons repeated the measurements after image sequence re randomization. Intraclass correlation coefficient (ICC) was calculated to evaluate IOR for each SPP. Intra-observer reliability (IAOR) was assessed through an average Pearson's correlation coefficient for each parameter for each surgeon. RESULTS: 16 surgeons completed initial measurements. IOR was poor for TPA (0.35, 95% CI 0.20, 0.58) and PI (0.42, 95% CI 0.26, 0.65) and fair for LL (0.67, 95% CI 0.51, 0.82) and PT (0.63, 95% CI 0.47, 0.81). 14 surgeons completed phase-2 measurements to assess IAOR. Average parameter PPC showed excellent IAOR (LL 0.86, TPA 0.77, PI 0.78, PT 0.86). Kappa coefficient showed fair agreement for raters choosing the same endplate for measurement (Phase 1 0.38, Phase 2 0.32). By patient, the percentage of raters that chose the S1 endplate for measurement varied from 6.3% to 85.7%. CONCLUSIONS: Significant variability exists when surgeons measure SPP in patients with LSTV. These parameters are critical in determining the goals of surgical reconstruction and such variability may have considerable implications for radiographic goals and outcomes of surgical reconstruction. LEVEL OF EVIDENCE: 4. PMID- 28984733 TI - Cartilage Endplate Thickness Variation Measured by Ultrashort Echo-Time MRI Is Associated With Adjacent Disc Degeneration. AB - STUDY DESIGN: A magnetic resonance imaging study of human cadaver spines. OBJECTIVE: To investigate associations between cartilage endplate (CEP) thickness and disc degeneration. SUMMARY OF BACKGROUND DATA: Damage to the CEP is associated with spinal injury and back pain. However, CEP morphology and its association with disc degeneration have not been well characterized. METHODS: Ten lumbar motion segments with varying degrees of disc degeneration were harvested from six cadaveric spines and scanned with magnetic resonance imaging in the sagittal plane using a T2-weighted two-dimensional (2D) sequence, a three dimensional (3D) ultrashort echo-time (UTE) imaging sequence, and a 3D T1rho mapping sequence. CEP thicknesses were calculated from 3D UTE image data using a custom, automated algorithm, and these values were validated against histology measurements. Pfirrmann grades and T1rho values in the disc were assessed and correlated with CEP thickness. RESULTS: The mean CEP thickness calculated from UTE images was 0.74 +/- 0.04 mm. Statistical comparisons between histology and UTE-derived measurements of CEP thickness showed significant agreement, with the mean difference not significantly different from zero (P = 0.32). Within-disc variation of T1rho (standard deviation) was significantly lower for Pfirrmann grade 4 than Pfirrmann grade 3 (P < 0.05). Within-disc variation of T1rho and adjacent CEP thickness heterogeneity (coefficient of variation) had a significant negative correlation (r = -0.65, P = 0.04). The standard deviation of T1rhoand the mean CEP thickness showed a moderate positive correlation (r = 0.40, P = 0.26). CONCLUSION: This study demonstrates that quantitative measurements of CEP thickness measured from UTE magnetic resonance imaging are associated with disc degeneration. Our results suggest that variability in CEP thickness and T1rho, rather than their mean values, may serve as valuable diagnostic markers for disc degeneration. LEVEL OF EVIDENCE: N/A. PMID- 28984736 TI - EFFECT OF PATIENTS' CLINICAL INFORMATION ON THE DIAGNOSIS OF AND DECISION TO TREAT RETINOPATHY OF PREMATURITY. AB - PURPOSE: To evaluate the effect of patients' clinical information on experts' diagnoses of retinopathy of prematurity (ROP) and decisions to treat. METHODS: Seven experts assessed wide-field fundus photographs of eyes of 52 premature infants of <=30 weeks' gestational age or <=1,500 g birthweight (BW) for ROP diagnosis (stage, plus disease, and aggressive posterior ROP) and the necessity for treatment for 2 days. On Day 1, they were masked to all patient data. On Day 2, they were given information on gestational age and BW. RESULTS: A significant shift in the experts' ratings toward a less aggressive ROP grading stage (P = 0.006) and less frequent decision for intervention (P = 0.021) was observed after receipt of patients' clinical information. This was truer for heavier/less premature infants (gestational age >= 28 0/7 weeks or BW >= 900 g) than those with very low BWs/high prematurity (gestational age < 24 0/7 weeks or BW < 600 g) (ROP stage P = 0.009 vs. P = 0.399, treatment decision P = 0.022 vs. P = 0.648). CONCLUSION: These results suggest knowledge of patients' clinical information influences the grading of ROP disease and decision for treatment. Retinopathy of prematurity staging seemed to be set at a lower level and the decision for treatment at a higher threshold for heavier/less premature babies. Our findings may have implications for further refinements in ROP assessment. PMID- 28984737 TI - INTRAVITREAL AFLIBERCEPT AND RANIBIZUMAB INJECTIONS FOR TYPE 3 NEOVASCULARIZATION. AB - PURPOSE: To compare the effectiveness of intravitreal injection of aflibercept with ranibizumab in patients with Type 3 neovascularization. METHODS: Sixty-three treatment-naive eyes with Type 3 neovascularization (58 patients) were retrospectively analyzed. The eyes had received intravitreal aflibercept or ranibizumab injections. All patients were treated using an initial series of three monthly loading injections, followed by further injections as required. The visual and anatomical outcomes of treatment were evaluated after 12 months. RESULTS: The mean best-corrected visual acuity in the aflibercept-treated group (21 eyes), expressed as the logarithm of the minimum angle of resolution, improved from 0.71 +/- 0.42 (Snellen equivalent; 20/102) to 0.54 +/- 0.39 (20/69) after 12 months of treatment (P = 0.022). Similarly, in the ranibizumab-treated group (42 eyes), the best-corrected visual acuity improved from 0.68 +/- 0.38 (20/95) to 0.53 +/- 0.36 (20/67) (P = 0.013) at 12 months. The central foveal thickness decreased in the aflibercept-treated group from 356 +/- 139 MUm to 212 +/- 155 MUm and in the ranibizumab-treated group from 348 +/- 177 MUm to 208 +/- 161 MUm (P = 0.014 and P = 0.017, respectively). There was no significant difference between the groups about improvement in best-corrected visual acuity or decrease in central foveal thickness. However, geographic atrophy was significantly more frequent in the aflibercept-treated group, occurring in 42.9% of eyes, than in the ranibizumab-treated group (19.0% of eyes; P = 0.045). CONCLUSION: There was no difference between the aflibercept and ranibizumab treatments in terms of visual acuity improvement after 12 months in patients with Type 3 neovascularization. However, geographic atrophy developed more frequently in the aflibercept-treated group. PMID- 28984738 TI - Outer Retinal Tubulation Associated With Chronic Retinal Detachment. PMID- 28984739 TI - Correspondence. PMID- 28984740 TI - Correspondence. PMID- 28984741 TI - Foveal Retinal Neovascularization in Proliferative Diabetic Retinopathy: Assessment by Optical Coherence Tomography Angiography. PMID- 28984742 TI - Correspondence. PMID- 28984743 TI - ARTERIAL OXYGEN SATURATION IN NEOVASCULARIZATIONS IN PROLIFERATIVE DIABETIC RETINOPATHY. AB - PURPOSE: Retinal neovascularizations in proliferative diabetic retinopathy have been proposed to develop from larger retinal venules. However, angiographic evidence suggests that the new vessels may originate from both arterioles and venules, and the vitreous oxygen tension near retinal neovascularizations is similar to that of retinal arterioles. An assessment of the oxygen saturation in neovascularizations may help characterizing the vascular origin of these vessels in proliferative diabetic retinopathy. METHODS: Dual wavelength oximetry was used to study the oxygen saturation in arterioles, venules, and retinal neovascularizations in 40 eyes from 40 patients with proliferative diabetic retinopathy. RESULTS: The oxygen saturation was significantly lower in retinal venules than in arterioles and neovascularizations (P < 0.0001), and after a correction for the influence of vessel diameter, there was no significant difference between the oxygen saturation in retinal arterioles and neovascularizations (P = 0.71). Age at onset and duration of diabetes mellitus contributed significantly to the variation in oxygen saturation of the venules, whereas none of the clinical background parameters contributed to the variation in oxygen saturation in arterioles and neovascularizations. CONCLUSION: The oxygen saturation in retinal neovascularizations in proliferative diabetic retinopathy is similar to that of the arterioles. Neovascularizations may act as shunts to bypass areas of capillary occlusion. PMID- 28984744 TI - Correspondence. PMID- 28984745 TI - Reply. PMID- 28984747 TI - Thirty- Versus Ten-Day Diazepam Treatment for Alcohol Detoxification and a Comparison of Drinking Patterns, Craving, and Anxiety for up to 12 Weeks: A "Proof-of-Concept" Open-Label Randomized Controlled Trial. AB - PURPOSE: The aim of this study was to evaluate whether a prolonged detoxification treatment could decrease the relapse rate at 3 months after alcohol cessation in alcohol-dependent individuals through decreasing the levels of postdetoxification craving and anxiety. METHODS: Twenty-six adult patients with alcohol dependence (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision) who began an outpatient alcohol cessation program with an initial drinking goal of abstinence were enrolled in a 3-month, parallel, randomized (1:1 ratio), controlled, open-label, pilot trial. Participants were randomized to receive a detoxification treatment of diazepam with a duration of 30 (n = 12) or 10 days (n = 14). All participants received BRENDA-based psychotherapy during follow-up. RESULTS: No significant between-group difference in relapse to any drinking was found at 3 months (P = 0.20). However, relapse to any heavy drinking at 3 months and regular drinking or heavy drinking during follow-up were significantly lower in the 30-day diazepam group (P = 0.009, P = 0.049, and P = 0.004, respectively). These differences were corroborated by significant differences in the alcohol-specific biological marker carbohydrate deficient transferrin at 3 months. Participants in the 30-day diazepam group also displayed significantly lower scores for alcohol craving (P = 0.007), self-reported anxiety (P = 0.024), and clinician-assessed anxiety (P = 0.002) throughout the follow-up. No serious adverse event was reported during the study. CONCLUSION: This study provides an evidence-based rationale for a double-blind, randomized, placebo controlled trial to confirm the efficacy of such a procedure on short-term and mid-/long-term drinking outcomes after alcohol cessation in alcohol-dependent individuals. PMID- 28984746 TI - Late Reduction of Cocaine Cravings in a Randomized, Double-Blind Trial of Aripiprazole vs Perphenazine in Schizophrenia and Comorbid Cocaine Dependence. AB - PURPOSE: Co-occurring schizophrenia spectrum disorder and International Statistical Classification of Diseases, 10th Revision cocaine dependence present a particularly destructive constellation that is often difficult to treat. Both conditions raise dopamine transmission effects in the brain. Traditional neuroleptics block dopamine receptors, whereas aripiprazole modulates dopamine activity as an agonist/antagonist. We tested whether dopamine modulation is superior to dopamine blocking in dual-diagnosis patients. METHODS: In a randomized, double-blind, comparison design, cocaine-dependent schizophrenic subjects actively using cocaine received either aripiprazole or perphenazine in an 8-week trial. Primary outcome targeted cocaine-free urine sample proportions, whereas cocaine craving scores were a secondary variable. RESULTS: Subjects (N = 44) randomized (n = 22 per group) did not differ at baseline. The proportion of cocaine-free urine samples did not differ by medication group. Contrasting weeks 3 to 5 vs 6 to 8 revealed significant late reductions in craving with aripiprazole. On the respective 5-point subscales, craving intensity decreased by 1.53 +/- 0.43 (P < 0.0005) points, craving frequency by 1.4 +/- 0.40 (P > 0.0004) points, and craving duration by 1.76 +/- 0.44 (P > 0.0001) points. CONCLUSIONS: A drug effect of aripiprazole on craving items appeared at week 6 of treatment, on average, and was not seen before that length of drug exposure. The data suggest that dopamine modulation reduces cocaine cravings but requires an acclimation period. To understand the mechanism of action better, a trial of depot aripiprazole may be useful. Clinically, a reduction in craving potentially offers a clearer focus for ongoing behavioral treatment. It may also offer a longer-term treatment effect with respect to the severity of relapse. PMID- 28984748 TI - Clozapine-induced agranulocytosis/granulocytopenia: mechanisms and monitoring. AB - PURPOSE OF REVIEW: Clozapine-induced agranulocytosis/granulocytopenia (CIAG) is an uncommon condition, but potentially fatal in consequences. The pathogenesis, despite multiple experiments, is not fully elucidated. The current theory suggests reactive oxygen species - nitrenium ion as the most important factor of CIAG. In this review, mechanism and monitoring of CIAG will be discussed. RECENT FINDINGS: The mechanism of CIAG seems to have an autoimmune background, rather than toxic. Clozapine has a high potential to undergo biochemical activation to nitrenium ion. The role of the primary metabolite of clozapine - N desmethylclozapine - is in decline. Nitrenium ion is mainly synthesized by CYP3A4, CYP2D6, and myeloperoxidase system in leukocytes. An important component of CIAG pathogenesis is genetic aberration in human leukocyte antigen genes, and also genes associated with apoptosis and ubiquitination. Clozapine monitoring regimes differ between countries. US-derived clozapine Risk Evaluation and Mitigation Strategy is the most tolerant in the aspect of blood parameter thresholds. Therefore, it provides the opportunities for physician to continue the treatment and also to rechallenge the drug after the episode of CIAG. SUMMARY: Each patient with the episode of CIAG should be assessed individually, with special attention to risk factors and drug-drug interactions. Upon that, the decision about clozapine rechallenge or withdrawal should be made. PMID- 28984749 TI - INTRAVITREAL INJECTION OF AIR FOR THE TREATMENT OF VITREOMACULAR TRACTION. AB - PURPOSE: To study the efficacy of a single intravitreal injection of air as a valuable alternative to current treatment options (conservative, pharmacological, and surgical) in patients with symptomatic, focal vitreomacular traction. METHODS: Interventional, nonrandomized clinical study including a consecutive series of patients who underwent a single injection of 0.3 mL of air for vitreomacular traction. Each patient underwent best-corrected visual acuity, and spectral domain optical coherence tomography before and after the procedure. Mean maximal horizontal vitreomacular adhesion and a maximal foveal thickness were measured manually. RESULTS: Four eyes of four patients, all males, were included in the study. Mean age was 71 +/- 6.7 years; mean best-corrected visual acuity was 0.3 +/- 0.08 logarithm of the minimum angle of resolution (logMAR) (20/40 Snellen equivalent). One month following treatment, complete resolution of vitreomacular traction was achieved in 100% of eyes. Mean visual acuity postinjection was 0.18 +/- 0.09 logMAR (20/32 Snellen equivalent) (Student's t test for repeated measures P = 0.03). No correlation has been found between horizontal vitreomacular adhesion and best-corrected visual acuity or maximal foveal thickness and best-corrected visual acuity (P = 0.7 and P = 0.9, respectively). CONCLUSION: Intravitreal injection of air could offer a minimally invasive, low-cost alternative treatment in patients with symptomatic, persisting vitreomacular traction. Additional studies on a larger number of patients are required. PMID- 28984750 TI - Postoperative changes of liver enzymes can distinguish between biliary stricture and graft rejection after living donor liver transplantation: A longitudinal study. AB - There is no known useful clinical parameter that can specifically predict a biliary stricture and differentiate it from other related complications after living donor liver transplantations (LDLT). The aims of this study were to determine whether the changes of liver enzymes can predict postoperative biliary stricture apart from other complications. We reviewed the medical records of 203 patients who underwent LDLT with duct to duct anastomosis from 2008 to 2010. The longitudinal changes of liver enzyme over time and the occurrence of complication were evaluated. A total of 124 patients had no complication up to 2 years after LDLT, and 74 patients had complications including biliary stricture and graft rejection. Complications developed more frequently in patients who's alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGT) did not return to the baseline plateau at 30 days after LDLT (ALP; P = .045, GGT; P = .047). Aspartate transaminase (AST) and alanine transaminase (ALT) increased continuously until the diagnosis of complication in both stricture and rejection groups with more rapid increase in enzymes in the rejection versus stricture group (P < .05). In addition, AST and ALT were 2-fold higher in the rejection than the stricture group at the diagnosis of each complication (AST; P < .05, ALT; P < .05). The increasing slope and final levels of AST and ALT are potentially helpful parameters to differentiate rejection and stricture, the 2 most common posttransplantation complications. PMID- 28984751 TI - Bla-OXA48 gene microorganisms outbreak, in a tertiary Children's Hospital, Over 3 years (2012-2014): Case Report. AB - RATIONALE: Carbapenem-resistant Enterobacteriaceae are an emerging problem in children. Nosocomial spread remains the principal risk factor for acquisition of these microorganisms. PATIENTS CONCERNS: We describe an outbreak of Klebsiella pneumoniae OXA48 (KOXA48) in a tertiary children's hospital during the years 2012 to 2014, as well as the preventive measures put in place in colonized and infected cases. DIAGNOSES: We studied, "in vitro," the KOXA48 susceptibility to antiseptics and surface disinfectants. Moreover, an epidemiological surveillance of infection or colonization by these microorganisms, with molecular typing of the KOXA48, was performed, and carbapenemase genes were confirmed by polymerase chain reaction (PCR). INTERVENTIONS: The bundles recommended (early detection, cohorting of children and health care workers [HCW], contact precautions, etc.) to control the KOXA48 outbreak were taken from those described in the centers for disease control (CDC) 2012 guide, and adapted according to our experience in controlling other outbreaks. OUTCOMES: All the KOXA48 microorganisms isolated from children belonged to the same strain (ST11) and were susceptible to alcohol solutions but not the surface disinfectant previously employed in our hospital (tensoactive). We reinforced the surface disinfection using a double application (tensoactive + alcohol). The outbreak of KOXA48 begun in 2012 (16 cases in neonatal intensive care unit [NICU] and 1 in pediatric intensive care unit [PICU]) ended before the end of the same year and was not transmitted to new patients in 2013 to 2014, despite readmission of some colonized cases, in intensive care units (ICUs) and other units, of our children hospital. LESSONS: Infected children are the tip of the iceberg (3/17) of KOXA48 prevalence making it necessary to identify the cases colonized by these bacteria. At the beginning of the outbreak, the susceptibility of the epidemic strain to antiseptics and surface disinfectants should be studied. Moreover, the measures taken (cohorts, contact precautions, etc.) must be thorough in both colonized and infected cases, immediately, after microbiological diagnosis. PMID- 28984752 TI - Intensity-modulated radiation therapy for patients with 1 to 3 brain metastases in recursive partitioning analysis class 3. AB - The prognosis is extremely poor for patients with brain metastases in recursive partitioning analysis (RPA) class 3. It is not clear whether dose elevation for brain lesions in addition to whole-brain radiotherapy could improve survival for those patients. This study aimed to assess the efficacy and safety of dose elevation with intensity-modulated radiation therapy (IMRT) for patients with 1 to 3 brain metastases in RPA class 3.From January 2013 to December 2015, 24 patients with 1 to 3 brain metastases in RPA class 3 were included in this study. The median age was 60 (range 41-85) years and the mean graded prognostic assessment (GPA) score was 1.25 (range 0.5-2). Whole-brain radiotherapy (30 Gy) with a simultaneous integrated boost (SIB) to the brain metastases (totaling 40 Gy) was delivered in 10 fractions using IMRT technique. Survival times and overall safety were assessed. The significance of prognostic variables on survival was assessed by both univariate and multivariate analyses.All of the patients completed the planned SIB schedule. The overall response rate was 66.7%. The median survival time (MST) was 8 months for the entire group of patients. The MST was 5 months for patients with a GPA score of 0.5 to 1 (n = 11 patients) and 12 months with a GPA score of 1.5 to 2 (n = 13 patients). No acute or late toxicities greater than grade 2 were detected. Age and subsequent chemotherapy were significantly associated with MST on univariate and multivariate analyses.It is feasible to elevate radiation doses to 40 Gy using the IMRT technique in RPA class 3 patients with 1 to 3 brain metastases without serious toxicities. The preliminary results are encouraging and further studies with larger cohorts are warranted. PMID- 28984753 TI - Cervical epidural analgesia complicated by epidural abscess: A case report and literature review. AB - RATIONALE: Spinal epidural abscess is an uncommon complication in clinical practice. If the abscess is large enough, the patient will rapidly develop neurologic signs of spinal injury, and urgent neurosurgical intervention may be required. PATIENT CONCERNS: Rapid and correct diagnosis and treatment is important for spinal epidural abscess complication. DIAGNOSES: This report describes a cervical epidural abscess (CEA) caused by epidural analgesia, wherein the patient was punctured twice. A CEA was suspected based on the patient's significant neck pain and elevated white blood cell and neutrophil counts. A CEA from C6 to T8 was confirmed by magnetic resonance imaging scan. INTERVENTIONS: The patient was treated with a combination of intravenous vancomycin and imipenem/cilastatin for more than 4 weeks. OUTCOMES: After more than 2 weeks of intensive antibiotic treatment, the epidural abscess gradually diminished in size, the white blood cell count, neutrophil count, hyperallergic C-reactive protein (CRP), and general CRP decreased, and the patient's neck and back pain resolved. After more than 4 weeks of anti-inflammation therapy, the epidural abscess was completely absorbed, and there was no relapse during the 3-month follow-up period. LESSONS: Although an effective combination of intravenous antibiotics can cure an epidural abscess, caution is warranted when performing epidural steroid injections in immunocompromised patients. PMID- 28984754 TI - Late presentation of necrotizing enterocolitis associated with rotavirus infection in a term infant with hyperinsulinism on octreotide therapy: A case report. AB - RATIONALE: Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycemia in infancy that can cause permanent brain damage. Consequently, optimal management is extremely important. Current pharmacologic and surgical treatment were available that included diazoxide and octreotides. PATIENT CONCERNS: A 4 month old Saudi male patient diagnosed at our hospital as CHI, treated with near total pancreatectomy and octreotide therapy of 30 mcg/kg/day presented with severe abdominal distension, vomiting and bloody diarrhea. DIAGNOSES: The patient was diagnosed as necrotising enterocolitis (NEC) associated with Rota virus infection which played together with octeriotides as risk factors for NEC. INTERVENTIONS: Radiological investigations and multidisciplinary team management with endocrinologist, neonatologist, pediatric surgeon, and gastroenterologist. OUTCOMES: Resolution of NEC with conservative medical management and was discharged after 1 month of hospital stay with follow up with all concerned sub specialties. LESSONS: NEC can develop in patients treated with octreotides especially when associated with another risk factor such as rotavirus infection. PMID- 28984755 TI - Clinical and imaging features of spinal cord type of neuro Behcet disease: A case report and systematic review. AB - RATIONAL: To investigate the clinical and MRI characteristics of spinal cord nerve Behcet's disease. PATIENT CONCERNS: One patient with spinal cord nerve Behcet's disease was admitted to our hospital at October 20, 2015. DIAGNOSE: Spinal cord nerve Behcet's disease. INTERVENTIONS: Retrospective analysis was performed on such case as well as 16 cases of spinal cord nerve Behcet's disease reported in China or abroad. OUTCOMES: Seventeen cases of spinal cord type of neuro Behcet's disease include 13 men and 4 women, with an average age of onset of 34.8 years old. The mean time from Behcet's disease symptoms to spinal cord involvement were 10.8 years. The initial symptom in one case was spinal cord injury, and another 4 cases had a recurrence course. The most common performance of spinal cord injury was sensory disturbance (82.4%), following by weakness (76.5%), sphincter or sexual dysfunction (58.8%), and pain in back, backside of neck or lower chest (29.4%). The number of cells was slightly increased or the protein level was increased in cerebrospinal fluid test. And the water channel protein antibody and oligoclonal band of serum levels were all negative. The spinal cord injury involved more than 3 vertebral bodies in 10 cases, and involved more than half of spinal cord in sagittal plane in 8 cases. In acute stage, shock therapy with large dose of glucocorticoid was generally applied both in China and abroad. LESSONS: The clinical features of spinal cord nerve Behcet's disease were various, making it easily misdiagnosed. Longitudinal extensive transverse myelitis performs as a characteristic manifestation. PMID- 28984756 TI - Preoperative photocoagulation reduces corneal endothelial cell damage after vitrectomy in patients with proliferative diabetic retinopathy. AB - Proliferative diabetic retinopathy (PDR) is a severe complication of diabetes and is a leading cause of visual decline and irreversible blindness. So we designed this study to investigate retrospectively the effect of preoperative photocoagulation on corneal endothelial cells after vitrectomy in patients with PDR.The study included 52 eyes of 46 patients with PDR complicated with vitreous hemorrhage, who underwent vitrectomy. Patients were apportioned to a photocoagulation group (26 eyes/23 patients) or nonphotocoagulation group (26/23 patients), according to their history of preoperative photocoagulation. A specular microscope was used to assess the corneal endothelial cell density and percentage of hexagonal cells (PHC) before surgery, and at 1 week, 1 month, and 3 months after surgery.The cell density was lower 3 months after surgery in the photocoagulation group, but at 1 month in the nonphotocoagulation group, all cases were significantly different from the preoperative value (P < .05 or P < .01). One week after surgery, the mean cell densities between the photocoagulation and nonphotocoagulation groups were not statistically different (P > .05). However, the mean cell densities at 1 and 3 months after surgery in the photocoagulation group were significantly higher than those in the nonphotocoagulation group (P < .05). The PHC values in the photocoagulation group at 1 week and in the nonphotocoagulation group at 1 week, 1 month, and 3 months were much lower than their respective preoperative values (P < .05 or P < .01). More importantly, at 1 and 3 months, the PHC had recovered to preoperative values in the photocoagulation group, but not in the nonphotocoagulation group. As for cell density and PHC, they were both significantly higher 1 and 3 months after surgery in the photocoagulation group than in the nonphotocoagulation group (P < .05).Photocoagulation before vitrectomy reduces subsequent corneal endothelial cell damage in PDR patients. PMID- 28984758 TI - Expression of matrix metalloproteinases-12 in ST-segment elevation myocardial infarction: A case-control study. AB - Matrix metalloproteinases-12 (MMP12) can lead to degradation of elastin resulting in plaque destabilization and rupture. MMP12 also facilitates platelet aggregation, adhesion, and granule secretion. However, evidence in the literature related to the function of MMP12 in ST-segment elevation myocardial infarction (STEMI) is little. This study investigated the expression of MMP12 in human coronary thrombus and examined the relationship between plasma MMP12 and STEMI.Arterial plasma was obtained from 46 STEMI patients and 52 stable angina pectoris (SAP) patients and 30 controls with angiographically normal coronary arteries. Coronary thrombi were obtained from 26 STEMI patients with a large thrombus burden (LTB). The expression levels of MMP12 in coronary thrombus were analyzed by immunohistochemistry and immunofluorescence, reverse transcription polymerase chain reaction (RT-PCR), Western blotting (WB) and casein zymography. In addition, MMP12 concentration measured by enzyme-linked immunosorbent assay (ELISA) and activity measured by fluorescence resonance energy transfer (FRET) were used to assess the levels in plasma.We confirmed the expression of MMP12 in human coronary thrombus. MMP12 was secreted mainly in active form of 45 kDa in coronary thrombus. In plasma samples of the STEMI group, MMP12 concentrations were found to be higher than the SAP group (5.030 +/- 2.24 pg/mL vs 3.010 +/- 1.99 pg/mL, P < .05) but with lower MMP12 activity (332 +/- 77 RFU vs 458 +/- 91 RFU, P < .05). Also, the STEMI group demonstrated much higher MMP12 concentrations than the normal coronary artery control group (5.030 +/- 2.24 pg/mL vs 1.720 +/- 0.51 pg/mL, P < .05) and with lower MMP12 activity (332 +/- 77 RFU vs 549 +/- 112 RFU, P < .05). In addition, the STEMI group had significantly higher tissue inhibitor of metalloproteinases-1 (TIMP1) concentration (573.40 +/- 270.60 pg/mL) than SAP group (384.50 +/- 147.70 pg/mL) and control group (219.90 +/- 154.80 pg/mL, P < .05). The imbalance in MMP12/TIMP ratio was observed in the STEMI group compared with SAP and control group (P < .05).This study demonstrated that MMP12 exists in human coronary thrombus. Patients with STEMI have elevated plasma level of MMP12 and the imbalance of MMP12/TIMP1. These data supported that MMP12 might be of potential relevance in STEMI. PMID- 28984757 TI - The association between diabetes/hyperglycemia and the prognosis of cervical cancer patients: A systematic review and meta-analysis. AB - BACKGROUND: The predictive roles of diabetes in the prognosis of many types of cancer have been well studied, but its role in predicting the prognosis of cervical cancer is still controversial. The aim of the study is to evaluate the association between diabetes/hyperglycemia and the prognosis of cervical cancer. METHODS: We conducted a systematic review for peer-reviewed studies indexed in PubMed, Embase, Web of Science, and Wanfang published before December 2016. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were pooled in the meta-analysis. RESULTS: This systematic review identified 13 studies with a total of 11,091 cervical cancer patients, of which 11 studies were included in the meta analysis. The study indicated that diabetes was related to poorer overall survival (HR = 1.59, 95% CI: 1.35-1.87, P < .001) and poorer recurrence-free survival (HR = 1.98, 95% CI: 1.47-2.66, P < .001) in cervical cancer patients. The meta-analysis of adjusted HRs also indicated that diabetes was independently associated with poor overall survival (HR = 1.69, 95% CI: 1.38-2.05, P < .001) and poor recurrence-free survival (HR = 1.98, 95% CI: 1.47-2.66, P < .001) in cervical cancer patients. Sensitivity analysis and subgroup analyses showed similar results. No significant heterogeneity was observed for the included studies. CONCLUSIONS: The meta-analysis suggests that diabetes is an important predictive factor for cervical cancer prognosis, and it is linked to poorer survival of cervical cancer patients. Diabetes can serve as a useful index in the prognostic evaluation for patients with cervical cancer. PMID- 28984759 TI - Serum levels of uncoupling proteins in patients with differential insulin resistance: A community-based cohort study. AB - The uncoupling protein (UCP) belongs to a family of energy-dissipating proteins in mitochondria. Increasing evidences have indicated that UCPs have immense impact on glucose homeostasis and are key proteins in metabolic syndrome. For applying the findings to clinical practice, we designed a study to explore the association between serum UCPs 1-3 and insulin resistance. This investigation prospectively recorded demographical parameter and collected blood samples of 1071 participants from 4 districts in Northeastern Taiwan during the period from August 2013 to July 2014. Propensity score matching by age and sex in patients with top and bottom third homeostasis model assessment of insulin resistance (HOMA-IR) levels was performed, and 326 subjects were enrolled for further studies. The mean age of the patients was 59.4 years and the majority of them (65.5%) were females. The prevalence of metabolic syndrome was 35.5%. Our results demonstrated that serum UCPs 1-3 were significantly associated with differences in HOMA-IR levels. Multiple logistic regression analysis indicated that low UCP 1 and features of metabolic syndrome, namely hypertension, diabetes, body mass index, and high-density lipoprotein, were independent determinants for high HOMA IR levels. We thus determined that low serum UCP 1 is a predictor for high resistance to insulin. PMID- 28984760 TI - Implementation effectiveness of revised (post-2010) World Health Organization guidelines on prevention of mother-to-child transmission of HIV using routinely collected data in sub-Saharan Africa: A systematic literature review. AB - BACKGROUND: To synthesize and evaluate the impact of implementing post-2010 World Health Organization (WHO) prevention of mother-to-child transmission (PMTCT) guidelines on attainment of PMTCT targets. METHODS: Retrospective and prospective cohort study designs that utilized routinely collected data with a focus on provision and utilization of the cascade of PMTCT services were included. The outcomes included the proportion of pregnant women who were tested during their antenatal clinic (ANC) visits; mother-to-child transmission (MTCT) rate; adherence; retention rate; and loss to follow-up (LTFU). RESULTS: Of the 1210 references screened, 45 met the inclusion criteria. The studies originated from 14 countries in sub-Saharan Africa. The highest number of studies originated from Malawi (10) followed by Nigeria and South Africa with 7 studies each. More than half of the studies were on option A while the majority of option B+ studies were conducted in Malawi. These studies indicated a high uptake of human immunodeficiency virus (HIV) testing ranging from 75% in Nigeria to over 96% in Zimbabwe and South Africa. High proportions of CD4 count testing were reported in studies only from South Africa despite that in most of the countries CD4 testing was a prerequisite to access treatment. MTCT rate ranged from 1.1% to 15.1% and it was higher in studies where data were collected in the early days of the WHO 2010 PMTCT guidelines. During the postpartum period, adherence and retention rate decreased, and LTFU increased for both HIV-positive mothers and exposed infants. CONCLUSION: Irrespective of which option was followed, uptake of antenatal HIV testing was high but there was a large drop off along later points in the PMTCT cascade. More research is needed on how to improve later components of the PMTCT cascade, especially of option B+ which is now the norm throughout sub-Saharan Africa. PMID- 28984762 TI - Ivabradine has a neutral effect on mortality in randomized controlled trials. AB - BACKGROUND: It has long been a controversial hotspot whether resting heart rate (RHR) is a risk factor or a marker for death. Ivabradine, a specific inhibitor of the If current in the sinoatrial node, is a pure RHR lowering agent. The study was aimed to investigate whether ivabradine would reduce more RHR, cardiovascular disease (CVD) mortality, and all-cause mortality than those placebo or beta blockers. METHODS: The authors performed a meta-analysis of 8 randomized controlled clinical studies (with 40,357 participants), and 3 studies of those which were ivabradine versus placebo (36,069 participants) and other 5 studies ivabradine versus beta-blockers (4288 participants) were available. The authors compared the association of the RHR reduction with death from CVD causes (2674 in 40,285 participants) and the rate of all-cause death (3143 deaths in 38,037 participants), and assessed improvement in death rates with the use of ivabradine. RESULTS: The change of RHR from baseline to endpoint was 8 to 16 beats/min (bpm) in ivabradine group, 1 to 8 bpm in placebo group, and 4 to 24 bpm in beta-blockers group. In ivabradine versus placebo, the reduced risks of CVD mortality and all-cause morbidity were not significantly (risk ratio [RR] 1.02; 95% confidence interval [CI] 0.91-1.14, P = .737; RR: 1.00, 95% CI: 0.92-1.09, P = .992, respectively). CVD and all-cause morbidity were similar for ivabradine versus beta-blockers (RR: 1.04; 95% CI: 0.80-1.37, P = .752; RR: 1.17, 95% CI: 0.53-2.60, P = .697, respectively). CONCLUSIONS: Ivabradine had a neutral effect on mortality, suggesting that a pure RHR lowering agent did not reduce CVD mortality, all-cause mortality and improve the lifespan. PMID- 28984761 TI - Effects of different anticoagulant drugs on the prevention of complications in patients after arthroplasty: A network meta-analysis. AB - BACKGROUND: After arthroplasty treatment, some complications commonly occur, such as early revision, infection/dislocation, and venous thromboembolism (VTE). This study aims to use a network meta-analysis to compare effects of 9 anticoagulant drugs (edoxaban, dabigatan, apixaban, rivaroxaban, warfarin, heparin, bemiparin, ximelagatran, and enoxaparin) in preventing postoperative complications in arthroplasty patients. METHODS: After retrieving PubMed, Embase, and Cochrane Library database from the inception to November 2016, randomized controlled trials were enrolled. The integration of direct and indirect evidences was performed to calculate odd ratios and the surface under the cumulative ranking curves. Nineteen eligible randomized controlled trials were included. RESULTS: The network meta-analysis results showed that compared with warfarin, edoxaban, apixaban, and rivaroxaban had a lower incidence rate in asymptomatic deep venous thrombosis, which indicated that edoxaban, apixaban, and rivaroxaban had better effects on prevention. Similarly, in comparison to enoxaparin, edoxaban and rivaroxaban had better effect; rivaroxaban was better than ximelagatran in preventive effects. Compared with apixaban, edoxaban, dabigatan, rivaroxaban, and enoxaparin had a higher incidence rate in clinically relevant non-major bleeding, which showed that preventive effects were relatively poor. In addition, the results of the surface under the cumulative ranking curves showed that rivaroxaban and bemiparin worked best on symptomatic deep venous thrombosis and pulmonary embolism. In terms of bleeding, apixaban and warfarin had better preventive effects. CONCLUSION: Our findings suggested that rivaroxaban may work better in terms of symptomatic deep venous thrombosis and pulmonary embolism, whereas apixaban had better preventive effects in bleeding. PMID- 28984763 TI - Epidemic hemorrhagic fever complicated with late pregnancy: A case report. AB - RATIONALE: Hantaviruses cause two forms of diseases in humans, namely hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome. Hantavirus infections can occur in pregnant women, and could influence the maternal and fetal outcomes, although this is a rare finding, even in endemic areas. PATIENT CONCERNS: In this report, we describe anunusual case involving a pregnant woman with HFRS who was in a state of shock. DIAGNOSES: Hemorrhagic fever with renal syndrome and septic shock. INTERVENTIONS: Timely termination of pregnancyalong with correction of the shock is very important to curb the inflammation and reduce organ damage. OUTCOMES: Although HFRS in pregnancy could pose a serious threat to the lives of the mother and the child. Our patient was successfully treated. LESSONS: Early and accurate diagnosis, anti-shock treatment, and timely termination of pregnancyare the key aspects of therapy for HFRS with late pregnancy. PMID- 28984764 TI - A systematic review and meta-analysis of the prevalence of norovirus in cases of gastroenteritis in developing countries. AB - BACKGROUND: While norovirus (NoV) is well known as a leading causal pathogen for acute gastroenteritis in developed countries,structured data on prevalence in developing countries are not available thus far. This review aims to estimate the prevalence of NoV in cases of gastroenteritis in developing countries based on recently published reports. METHODS: Relevant studies were identified by searching PubMed and Web of Science for the period January 1, 1990 through March 31, 2016. We included studies performed in developing countries with a study period of at least 12 months and which provided information on polymerase chain reaction (PCR)-confirmed NoV prevalence in patients diagnosed with acute gastroenteritis. A metaanalysis was conducted on NoV prevalence, focused on viral genogroups GI and GII, in cases of acute gastroenteritis. RESULTS: Using evidence from 178 articles, the estimated NoV prevalence among 148,867 patients with acute gastroenteritis was 17% (95% confidence interval [CI]: 15-18%). The prevalence decreased from 18% (95% CI: 16-20%) for upper middle-income countries to 15% (13 18%) and 6% (3-10%) for lower middle- and low-income countries, respectively. There were no significant differences in NoV prevalence by age group (under 5 years, 5 years and over, and mixed ages) or severity of symptoms as defined by community, outpatient, or inpatient setting. The pooled prevalence of NoV GII (15%, 95% CI: 13-17%) was significantly higher than that of NoV GI (1%, 95% CI: 1 1%) in patients with acute gastroenteritis. CONCLUSION: From the evidence considered in this review, the estimated prevalence of NoV in patients with acute gastroenteritis in developing countries was 17%. This estimate can be used to evaluate the burden of NoV-associated acute gastroenteritis in developing countries, which is currently unclear due to poor diagnosis and surveillance systems, and the estimation may enhance the development of human NoV vaccines. PMID- 28984765 TI - Cutaneous sarcoidosis: A retrospective case series and a hospital-based case control study in Taiwan. AB - Sarcoidosis is a systemic granulomatous disorder of unknown etiology often involving skin. Studies on cutaneous sarcoidosis and comorbidities are limited. This study is aimed to describe the clinical features of cutaneous sarcoidosis diagnosed in our hospital and to determine the relationships between cutaneous sarcoidosis and comorbidities.This retrospective study evaluates patients with cutaneous sarcoidosis in a tertiary center in Taiwan from 1996 to 2015. The records of 38 patients with cutaneous sarcoidosis were reviewed for clinical characteristics and evaluated by analysis of variance. A 1:4 case-control analysis was conducted with 152 age- and sex-matched controls who underwent biopsy for other benign skin tumors.The male to female ratio was 1:4.4. The average age at diagnosis was 51.7 years. Female patients were on average 13.9 years older than male patients. The correlation of age with gender was statistically significant (P = .037). The most common cutaneous lesions were plaques (47.4%) and confined to the face (71.1%). Of the 38 patients, 26.3% had diabetes mellitus. Age over 40 (P = .014) and female (P = .014) were associated with facial involvement. In the case-control study, a higher percentage of patients with cutaneous sarcoidosis than of control subjects had diabetes mellitus (P = .001), hearing loss (P = .031) and eye diseases (P = .047).The present study demonstrates a striking female predominance and high proportions of facial involvement. Diabetes mellitus, hearing loss, and eye diseases may be associated with Taiwanese patients with cutaneous sarcoidosis. PMID- 28984766 TI - Flattening effect of corneal cross-linking depends on the preoperative severity of keratoconus. AB - A retrospective observational study was conducted to validate the effect of corneal cross-linking (CXL) on eyes with progressing keratoconus, depending on severity.In total, 45 eyes of 33 patients (age: 23.9 +/- 6.8 years, range: 14-42 years) with progressive keratoconus who underwent CXL were enrolled. Examinations were performed at pre-, 1, 3, 6, and 12 months after surgery. In addition to a slit lamp microscopy, measurement of visual acuity, the steepest keratometric value (Kmax), the thinnest corneal thickness (TCT), and the corneal endothelial cell density (ECD) were assessed. Change in Kmax (DeltaKmax) was calculated by subtracting the preoperative Kmax from the 12-month postoperative Kmax.CDVA, TCT, and ECD did not change significantly throughout the follow-up period. Kmax was 56.4 +/- 7.2 D preoperatively and 54.3 +/- 5.6 D at 12 months after CXL (P = .174). The average value of DeltaKmax was -2.23 +/- 4.31 D at 12 months after CXL. DeltaKmax was negatively correlated with preoperative Kmax (rho = -0.5517, P = .0001), and positively correlated with preoperative TCT (rho = 0.4791, P = .0012). However, no correlation was observed between Kmax and patient age or the decrease ratio of ECD.The more flattening was obtained after CXL in cases with the more advanced keratoconus. No complication, including corneal endothelial damage, was observed even in advanced cases. PMID- 28984767 TI - Outcomes of robotic versus laparoscopic surgery for mid and low rectal cancer after neoadjuvant chemoradiation therapy and the effect of learning curve. AB - Randomized controlled trials have demonstrated that laparoscopic surgery for rectal cancer is safe and can accelerate recovery without compromising oncological outcomes. However, such a surgery is technically demanding, limiting its application in nonspecialized centers. The operational features of a robotic system may facilitate overcoming this limitation. Studies have reported the potential advantages of robotic surgery. However, only a few of them have featured the application of this surgery in patients with advanced rectal cancer undergoing neoadjuvant chemoradiation therapy (nCRT).From January 2012 to April 2015, after undergoing nCRT, 40 patients with mid or low rectal cancer were operated using the robotic approach at our institution. Another 38 patients who were operated using the conventional laparoscopic approach were matched to patients in the robotic group by sex, age, the body mass index, and procedure. All operations were performed by a single surgical team. The clinicopathological characteristics and short-term outcomes of these patients were compared. To assess the effect of the learning curve on the outcomes, patients in the robotic group were further subdivided into 2 groups according to the sequential order of their procedures, with an equal number of patients in each group. Their outcome measures were compared.The robotic and laparoscopic groups were comparable with regard to pretreatment characteristics, rectal resection type, and pathological examination result. After undergoing nCRT, more patients in the robotic group exhibited clinically advanced diseases. The complication rate was similar between the 2 groups. The operation time and the time to the resumption of a soft diet were significantly prolonged in the robotic group. Further analysis revealed that the difference was mainly observed in the first robotic group. No significant difference was observed between the second robotic and laparoscopic groups.Although the robotic approach may offer potential advantages for rectal surgery, comparable short-term outcomes may be achieved when laparoscopic surgery is performed by experienced surgeons. However, our results suggested a shorter learning curve for robotic surgery for rectal cancer, even in patients who exhibited more advanced disease after undergoing nCRT. PMID- 28984768 TI - The safety and feasibility of guidezilla catheter in complex coronary interventions and an observational study. AB - The monorail Guidezilla guide extension catheter was designed to provide additional backup and facilitate device delivery in percutaneous coronary intervention (PCI) for complex coronary anatomy such as chronic total occlusion (CTO), extreme vessel tortuosity, diseased bypass grafts, and anomalous coronary arteries, among others.The present retrospective, single-center study included 188 consecutive patients who underwent PCI using the Guidezilla catheter from March 2015 to August 2016. Study outcomes were rates of target lesion crossing success, procedural success, and complications.The Guidezilla catheter was used most commonly in PCI of CTOs (45%) and heavy proximal calcification (37%), followed by tortuosity (10%), previously deployed proximal stents (4%), and coronary artery anomaly (4%). The right coronary artery (48%) was most commonly intervened followed by the left ascending (35%) and left circumflex (17%) arteries. Rates of target lesion crossing success and procedural success were both 99%, with one device-related periprocedural complication, namely proximal vessel dissection secondary to deep insertion which was successfully treated with stent implantation. Ninety percent of PCI were performed and completed successfully by radial access.In a single center with experienced operators, the use of the Guidezilla guide extension catheter in PCI of complex coronary anatomy performed mostly via radial artery access appeared safe and efficacious, and greatly facilitated device delivery. PMID- 28984769 TI - Conservative treatment for equinus deformity in children with cerebral palsy using an adjustable splint-assisted ankle-foot orthosis. AB - BACKGROUND: A novel splint, the assisting ankle-foot orthoses (AFO), was developed to provide adjustable sustained stretching to improve conservative treatment for equinus deformities in children with cerebral palsy (CP). The treatment effect was validated by follow-up visits. METHODS: This study involved subjects between 2 and 12 years old, including 28 CP children treated with splint assisted AFO correction, 30 CP children treated with static AFO correction, and 30 normal children with typical development (TD). Quantitative pedobarographic measurements were taken to evaluate the effect of splint-assisted AFO correction. The heel/forefoot ratio was introduced to indicate the degree of the equinus deformity during treatment. RESULTS: The results showed that the heel/forefoot ratios were 1.41 +/- 0.26 for the TD children; 0.65 +/- 0.41, 1.02 +/- 0.44, and 1.24 +/- 0.51 for the splint-assisted AFO correction before and after 6-month and 12-month treatments; 0.59 +/- 0.37, 0.67 +/- 0.44, and 0.66 +/- 0.42 for the static AFO correction before and after 6-month and 12-month treatments. CONCLUSIONS: This study suggests that correction with the adjustable splint assisted AFO is an effective treatment for equinus deformity in CP Children. PMID- 28984770 TI - Management of iatrogenic renal arteriovenous fistula and renal arterial pseudoaneurysm by transarterial embolization: A single center analysis and outcomes. AB - The purpose of this study was to evaluate the efficacy and safety of transarterial embolization (TAE) for iatrogenic renal arterial pseudoaneurysm and arteriovenous fistula at our center.Our retrospective analysis included 27 patients who received TAE for iatrogenic renal arterial pseudoaneurysm and arteriovenous fistula between January 2006 and January 2016. Data on demographics, type of minimally invasive renal procedures, clinical manifestation, imaging features, embolization procedure, and perioperative details were collected. The technical and clinical success rates were analyzed. Furthermore, the changes in serum creatinine and eGFR before and after embolization were recorded and compared by t test.The median time between iatrogenic renal injury and TAE was 3 days (range, 0-110 days), with most patients (24/27, 88.9%) receiving TAE within 14 days. Only 1 patient was diagnosed with renal artery pseudoaneurysm 110 days after laproscopic partial nephrectomy. The technical and clinical success rates were 100% and 96.3%, respectively, with 1 patient requiring a second embolotherapy at the third postoperative day. No other patient required additional endovascular or surgical intervention due to recurrent hemorrhage. The mean serum creatinine before TAE was 92.8 +/- 25.3 MUmol/L and after TAE, 96.1 +/- 27.7 MUmol/L (P = .095). The eGFR of pre- and postembolization was 75.2 +/- 26.5 mL/min/1.73 m and 72.5 +/- 26.2 mL/min/1.73 m (P = .16). No severe complications were observed during follow up.This retrospective review demonstrated that TAE for the treatment of iatrogenic renal artery pseudoaneurysm and/or arteriovenous fistula was safe and associated with high technical and clinical success rate. PMID- 28984771 TI - Application of neoadjuvant chemotherapy in occult breast cancer: Five case reports. AB - RATIONALE: Although rare, occult breast cancer (OBC) originates from breast tissue. Its primary lesions cannot be identified by clinical examination or imaging; therefore, the diagnosis, treatment, and prognosis remain controversial. PATIENT CONCERNS: This study comprised 5 female OBC patients who were admitted to the Affiliated Hospital of Guizhou Medical University for painless axillary lumps. DIAGNOSES: F-flurodeoxyglucose (F-FDG) positron emission tomography/computed tomography (PET/CT) indicated metastasis in the ipsilateral axillary lymph nodes. No clear breast primary lesions were identified; other organs were also excluded as the primary site. Pathological biopsy confirmed axillary lymph node metastasis of adenocarcinoma. Immunohistochemical staining of the tumor to identify the source revealed that estrogen receptors (ERs) and progesterone receptors (PgRs) were positive in 2 cases, ER was positive and PR was negative in 1 case, and both were negative in 2 cases. Human epidermal growth factor receptor 2 was negative in all cases. All patients were diagnosed with OBC. INTERVENTIONS: All patients underwent neoadjuvant chemotherapy (NAC). One patient did not undergo follow-up therapy. The other 4 underwent total mastectomy plus axillary lymph node dissection followed by radiotherapy. Two patients also underwent endocrine therapy. OUTCOMES: Patients were followed up for 9.0 to 72.0 months. Four achieved pathological complete response. One patient experienced metastasis to the ipsilateral supraclavicular lymph nodes 2.0 years later, which was cleared after additional treatment. The other patients were tumor free. LESSONS: Here, we are reporting 5 cases of OBC treated with NAC that were evaluated by F-FDG PET/CT scans. This study suggests that NAC might lead to a positive outcome. PMID- 28984772 TI - Comparison of 2 modified methods for the active removal of silicone oil with a 23 gauge transconjunctival vitrectomy system. AB - To report and compare 2 modified approaches for the active removal of silicone oil (ROSO) with a 23-gauge transconjunctival vitrectomy system.This prospective single blinded study was conducted from January 2015 to December 2016. Eighty nine eyes of 86 patients who underwent silicone oil removal were enrolled. Patients were randomly divided into either group A or B. In group A, the fluid air exchange tube was connected to a 1 mL syringe with the plunger removed and the tip was dilated with a hemostat so that it fit into the cap of the 23-gauge cannula to form a seal for oil drainage. In group B, the tip of the syringe was closely attached to the cap of the 23-gauge cannula by a tube adaptor, which was salvaged from a used silicone oil inject and aspirate pack and sterilized. Main outcome measures were time required for silicone oil removal, silicone oil residual, intraoperative and postoperative complications including hypotony, bleeding, and retinal redetachment.The mean time required was 6.08 +/- 0.31 minutes and 6.11 +/- 0.31 minutes for groups A and B, respectively. No silicone oil residual, severe hypotony, recurrence of retinal detachment, or impairment of visual acuity were observed in either group. Conjunctival injection and hyperemia were slightly more severe in group A, but spontaneously resolved in 2 to 3 days.Both methods described in this paper were demonstrated to be safe, effective, and cost-effective for the ROSO. The syringe dilation method caused more severe conjuntival irritation, thus we suggest using the tube adaptor method for hospitals equipped with cold sterilization equipment. PMID- 28984774 TI - A case report of tongue metastasis from lung squamous cell carcinoma and literature review. AB - RATIONALE: Tongue metastasis from lung cancer is extremely rare, and the prognosis of these patients is rather poor. PATIENT CONCERS: A 56-year-old man was found a 4-cm cavity lesion in the left upper lobe, which was initially misdiagnosed as tuberculosis. DIAGNOSES: A case of lung squamous cell carcinoma that metastasized to the base of a patient's tongue. INTERVATIONS: We send the biopsy of the lung and the tongue lesions for gene sequencing. OUTCOMES: He received systemic chemotherapy, but continued to have pain at the base of his tongue and died 7 months later. LESSONS: From sequencing data, mutations in KRAS proto-oncogene, GTPase (KRAS), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), and tumor protein p53 (TP53) were found in the tumor biopsy of the patient. All of these were indicators of poor prognosis. PMID- 28984773 TI - Ovarian torsion of mixed epithelial tumor misdiagnosed as a malignancy in postmenopausal woman: A case report. AB - RATIONALE: Adnexal torsion is 1 of the most common emergency gynecological disease. It is more often diagnosed in reproductive age, but rarely in postmenopausal women. The clinical symptoms of adnexal torsion are nonspecific in postmenopausal women. Epithelial ovarian tumors are common in adults, and the risk of malignancy increases with age, especially after menopause. So, it is difficult to diagnose adnexal torsion precisely compared with reproductive women, and most cases of adnexal torsion with postmenopausal women are diagnosed as a malignancy preoperatively. We report a case of ovarian torsion with mixed epithelial tumor misdiagnosed as a malignancy in postmenopausal woman. PATIENT CONCERNS: A 65-year-old woman presented lower left abdominal pain, and there was slight abdominal distension, but no tenderness or rebound tenderness on abdominal palpation. DIAGNOSES: Radiologic assessments showed a huge multiseptated cystic mass with solid portion in the left ovary, and malignancy was suspected. The test for serum tumor markers revealed normal levels of cancer antigen 125 (CA-125). INTERVENTIONS: The patient underwent a laparotomy and there was torsion of the left ovary. We conducted frozen biopsy of left ovary for confirming malignancy before performing staging surgery. OUTCOMES: The result of a frozen section biopsy confirmed a borderline Brenner tumor associated with a benign mucinous tumor. Subsequently, total hysterectomy and right salpingo-oophorectomy were performed. The operation was completed without addition procedures LESSONS:: Ovarian torsion is benign in most cases and malignancy is rare. Although very rare, ovarian torsion can occur in postmenopausal women, and it should be taken into consideration that the possibility of malignancy is low in postmenopausal women with normal CA-125 levels. Instead of performing staging surgery, it appears to be appropriate to carry out surgery based on the result of intraoperative frozen section biopsy so that we were able to avoid unnecessary surgical procedures. PMID- 28984775 TI - Clinicopathological features of progressive renal involvement in TAFRO syndrome: A case report and literature review. AB - RATIONALE: TAFRO syndrome is a systemic inflammatory disease characterized by a constellation of symptoms: Thrombocytopenia, Anasarca, MyeloFibrosis, Renal dysfunction, and Organomegaly. Progressive renal insufficiency is a predominant symptom; however, the mechanism of acute kidney injury (AKI) remains unclear, probably because severe thrombocytopenia prevents kidney biopsy. We report a rare case of TAFRO syndrome with histologically confirmed renal involvement. PATIENTS CONCERNS: A 70-year-old man developed fever, anasarca, AKI, thrombocytopenia, and hepatosplenomegaly. DIAGNOSES: Plasma vascular endothelial growth factor and serum interleukin-6 levels were significantly elevated. The diagnosis of TAFRO syndrome was made based on his clinical and laboratory findings. Kidney biopsy was performed for the evaluation of AKI and provided a diagnosis of membranoproliferative glomerulonephritis-like lesions due to endothelial injury. Glomerular capillary lumens were extremely narrowed or occluded by endothelial swelling, and marked widening of the subendothelial space by electron-lucent material resulted in mesangiolysis and a double-contoured glomerular basement membrane with no immune complex deposits. INTERVENTIONS AND OUTCOMES: The patient required temporary hemodialysis due to oliguric AKI, but steroid therapy rapidly improved renal function. LESSONS: Typically, patients with progressive renal involvement in TAFRO syndrome rapidly develop oliguric or anuric AKI. This report suggests that the reduction of glomerular perfusion by glomerular endothelial injury might be a primary factor in the progressive AKI of TAFRO syndrome. Our case and the literature review indicate that steroid and/or biological therapies result in highly favorable renal outcomes in patients with progressive AKI in TAFRO syndrome. PMID- 28984776 TI - Intralesional versus intracoronary administration of glycoprotein IIb/IIIa inhibitors during percutaneous coronary intervention in patients with acute coronary syndromes: A meta-analysis of randomized controlled trials. AB - BACKGROUND: Glycoprotein IIb/IIIa inhibitors (GPIs) have been regarded as an adjuvant regimen to deal with no-reflow. However, whether intralesional (IL) administration of GPIs improves myocardial reperfusion without increasing bleeding in patients with acute coronary syndrome (ACS) compared with intracoronary (IC) administration has not been well addressed. Our meta-analysis aimed to evaluate the efficacy and safety of IL versus IC administration of GPIs for patients with ACS during percutaneous coronary intervention. METHODS: We systematically searched Medline, Embase, the Cochrane Central Register of Controlled Trials, and Cambridge Scientific Abstracts from January 2007 to May 2017. Thrombolysis in Myocardial Infarction (TIMI) 3 flow, corrected TIMI frame count (CTFC), and complete ST-segment resolution (>70%) were selected as the primary outcomes. Major adverse cardiac events (MACEs) were the secondary outcome, and major bleeding complications were the safety outcome. Data analysis was conducted using the Review Manager 5.3 software. RESULTS: Six randomized controlled trials were included in our meta-analysis. Compared with IC, IL obtained better results in terms of TIMI grade 3 flow [odds ratio (OR) 2.29; 95% confidence intervals (CIs) 1.31-4.01; P = .004], CTFC [weighted mean difference (WMD) -4.63; 95% CI -8.82 to -0.43; P = .03], and complete ST-segment resolution (OR 1.55; 95% CI 1.12-2.14; P = .008). There was a trend toward decreased MACE in the IL administration groups, which was not of statistical significance (OR 0.63; 95% CI 0.30-1.31; P = .22). No significant difference was found between the two groups in terms of in-hospital major bleeding events (OR 2.52; 95% CI .66 to 9.62; P = .18). CONCLUSION: IL administration yielded favorable outcomes in terms of myocardial tissue reperfusion as evidenced by the improved TIMI flow grade, CTFC, complete ST-segment resolution, and decreased MACE without increasing in hospital major bleeding events. The IL administration of GPIs can be recommended as the preferred regimen to guard against no-reflow. PMID- 28984777 TI - Anti-Ma2-associated limbic encephalitis with coexisting chronic inflammatory demyelinating polyneuropathy in a patient with non-Hodgkin lymphoma: A case report. AB - RATIONALE: We report the rare case of a 74-year-old man with anti-Ma2-associated paraneoplastic neurologic syndrome (PNS), and review and analyze the clinical manifestations, diagnosis, and treatment of the disease. PATIENT CONCERNS: The patient presented with a 5-month history of muscle weakness, progressive body aches, and weakness and numbness in both lower extremities. Before his hospitalization, he had experienced cognitive function decline; ptosis, inward gaze, and vertical gaze palsy in the right eye; and occasional visual hallucinations. Brain and spinal cord magnetic resonance imaging (MRI) yielded normal results. Anti-Ma2 antibodies were detected in both serum and cerebrospinal fluid. A 4-hour electroencephalogram showed irregular sharp slow waves and delta waves in the temporal region. Electromyography showed peripheral nerve demyelination. Positron-emission tomography/computed tomography (PET-CT) examination revealed hypermetabolism in the lymph nodes of the whole body. Biopsy of the lymph nodes showed non-Hodgkin lymphoma. DIAGNOSIS: A clinical diagnosis of lymphoma and PNS was made. INTERVENTIONS: The patient was treated with intravenous dexamethasone (15 mg/day) for 3 days. LESSONS: We have presented a rare case of a PNS involving both the central and peripheral nervous systems. The clinical features of this case indicated anti-Ma2-associated encephalitis and chronic inflammatory demyelinating polyneuropathy. PET-CT played a critical role in enabling early diagnosis and prompt treatment in this case. PMID- 28984778 TI - Diagnostic value of using multiplanar reformation images: Case report for rare endotracheal hamartomas. AB - RATIONALE: Pulmonary hamartomas are the most common benign tumor of the lung. Two types of pathologically similar hamartomas exist based on their location. These tumors have a low incidence, are rarely reported and frequently misdiagnosed because of lack of familiarity and/or understanding concerning their imaging features. PATIENT CONCERNS: Seventeen patients received treatment between June 2007 and May 2013 and had complete medical records. All of them had different degrees of cough and expectoration. Other symptoms include fever (5 cases), hemoptysis (4 cases), chest pain (3 cases), shortness of breath (2 cases), and dyspnea (1 case). DIAGNOSES: These patients all have pathologically confirmed, and informed the diagnosis of endobronchial hamartoma. INTERVENTIONS: Unenhanced and enhanced CT scans were performed using Toshiba Aquilion 64-slice and GE Lightspeed 64-slice CT scanners. The scan was performed from the superior thoracic aperture to the lateral costophrenic angle. The transaxial CT data was inserted into a Volume Wizard workstation to reconstruct images using MPR technique. OUTCOMES: The relationship between the location of the tumor and bronchi was clearly displayed on the axial images in only 2 patients. In all 17 patients, reconstructed MPR images were able to display the tumor parallel to the long axis of bronchi, thus facilitating in tumor identification and positioning along the bronchial tree. LESSONS: MPR images are valuable tools in the diagnosis of endobronchial hamartomas. Chiefly, these reconstructions aid in the detection of intratumoral fat/calcification and clearly demonstrate the tumors relationship and effect with the adjacent bronchi. PMID- 28984779 TI - Two-dimensional myocardial deformation in coronary vasospasm-related Takotsubo cardiomyopathy: A case report of a serial echocardiographic study. AB - RATIONALE: Although transient reduction in the left ventricular ejection fraction is characteristic of Takotsubo cardiomyopathy, little is known about the time course changes of myocardial deformation in coronary vasospasm-related Takotsubo cardiomyopathy. PATIENT CONCERNS: We retrospectively analyzed the time-course changes in left ventricle, right ventricle, and left atrium strain values in a patient with coronary vasospasm-related Takotsubo cardiomyopathy. We found that not only left ventricular strain but also left atrial strain was abnormal during acute Takotsubo cardiomyopathy due to coronary vasospasm. Right ventricular free wall strain was normal. DIAGNOSES: Coronary vasospasm-related Takotsubo cardiomyopathy. INTERVENTIONS: A serial echocardiographic study. OUTCOMES: The left ventricular strain was still subnormal despite a normalized left ventricular ejection fraction 2 months later. The left atrial strain was normal when the left ventricular ejection fraction normalized. LESSONS: From this limited experience, it is suggested that echocardiographic myocardial deformation analysis can provide more information than the standard ejection fraction in evaluating myocardial contractile function. PMID- 28984780 TI - Conversion of failed hemiarthroplasty to total hip arthroplasty: A short-term follow-up study. AB - Purpose of this study was to evaluate the outcomes of patients underwent hemiarthroplasty for proximal femoral fracture converted to total hip arthroplasty (THA).A total of 138 patients from October 2009 till October 2014 had conversion of their failed hemiarthroplasties following a proximal femoral fracture to total hip arthroplasty (THA) in Erfan and Milad hospitals, Tehran. We performed a prospective analysis of the outcome of conversion surgery in patients with failed hemiarthroplasty. The patients had clinical evaluations at 1 month, 6 months, 1 year, and annually thereafter. We used Harris Hip Score (HHS) to evaluate the results of conversion procedure in terms of relief of groin pain and functional improvement.Dislocation occurred in 6 patients (4.34%). The mean period of follow-up was 42 months (range 36-60 months). HHS score improved from mean preoperative score of 44.93 +/- 8.40 to 95.41 +/- 2.27 at final follow-up. The survivorship analysis with revision of HHS score was 89.1%. Existence of infection (P = .038) and time of primary operation to being symptomatic (P = .009) can predict the postoperative pain significantly.THA is a safe option which can lead to good functional and short-term and mid-term outcomes; and patients should be informed of the possibility of incomplete relief of groin pain or other symptoms postoperatively. PMID- 28984781 TI - Vesical transmigration of an intrauterine contraceptive device: A rare case report and literature review. AB - RATIONALE: Displacement of an intrauterine contraceptive device (IUD) is a rare and serious complication of IUD insertion. Theoretically, it can migrate to anywhere in the pelvic and abdominal cavity. However, it is not usual for an IUD to migrate to the bladder. PATIENT CONCERNS: In this case report, we reported a patient with chronic urinary symptoms caused by the migration of an IUD into the bladder. The displacement of the IUD led to contraception failure and IUD retention in the bladder for 5 years. DIAGNOSES: Pelvic ultrasonography (US), radiography, and cystoscopy examinations confirmed the migration of IUD in bladder. INTERVENTIONS: The patient underwent cystoscopy. OUTCOMES: The MCu IUD was successfully removed without any complications. LESSONS: Our study demonstrated that a missing IUD should be followed up and removed early to avoid possible serious complications. PMID- 28984782 TI - Chiari type I malformation with occult tethered cord syndrome in a child: A case report. AB - RATIONALE: Chiari type I malformation (CM1) and occult tethered cord syndrome (OTCS) are considered to be malformations associated with subtle structural abnormalities of the terminal filum. Few studies have reported patients with CM1 and OTCS. Treatment strategy for patients of CM1 associated with OTCS is controversial. PATIENT CONCERNS: A 14-year-old child was admitted with intermittent pain and numbness in the right upper limb. And he had urinary frequency, neck pain, back pain, and numbness simultaneously. The imaging examinations showed CM1, syringomyelia, small fat in the filum at the level of the L2 vertebral body but the conus medullaris at the aspect of the L1 vertebral body. DIAGNOSES: The child was diagnosed with CM1 associated with OTCS. INTERVENTIONS: Patient underwent sectioning of filum terminale (SFT) under electrophysiological monitoring during the first hospital and posterior fossa decompression (PFD) during the second hospital. OUTCOMES: After first discharge pain of the right upper limb was relieved, but he still felt numbness. And his numbness was relieved after second discharge. The imaging examinations also showed corresponding improvement during the 2-year follow-up period. LESSONS: For pediatric patients with CM1 and TCS, treatment trouble is not only to choose the staging operation or simultaneous operation but also staging procedures for treatment of 2 lesions. Detailed preoperative evaluation is essential for development of individualized surgical plan. Staging operation of firstly minimally invasive SFT and later PFD may be helpful for such cases owing to its positive effect on both the symptoms and imaging findings. PMID- 28984783 TI - The current status of treatment for colorectal cancer in China: A systematic review. AB - BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers all over the world, but its epidemiology is obviously different in various regions. METHODS: The treatment of CRC also has varying characteristics due to differences in economy, geography, disease onset, chemotherapy, and other factors, although international guidelines are used to guide the treatment of CRC in China. RESULTS: This paper summarizes the current status of CRC treatment, including surgical therapy, neoadjuvant radiotherapy and chemotherapy, postoperative chemotherapy, targeted therapy, maintenance therapy, and immunotherapy, according to the clinical situation in China, so as to provide better therapy and improve clinical practice for patients with CRC. CONCLUSION: This research shows that the treatment of colorectal cancer continues to progress, and the patient's efficacy and quality of life have improved. PMID- 28984784 TI - Severe hypokalemic paralysis and rhabdomyolysis occurring after binge eating in a young bodybuilder: Case report. AB - RATIONALE: Severe hypokalemia can be a potentially life-threatening disorder and is associated with variable degrees of skeletal muscle weakness. PATIENT CONCERNS: We report a case of severe hypokalemic paralysis and rhabdomyolysis in a 28-year-old bodybuilder. He was admitted to the emergency room due to progressive paralysis in both lower extremities, which had begun 12 hours earlier. He was a bodybuilder trainer and had participated in a regional competition 5 days earlier. He went on a binge, consuming large amounts of carbohydrates over 4 days, resulting in a gain of 10 kg in weight. DIAGNOSES: He had no family history of paralysis and this was his first attack. He strongly denied drug abuse, such as anabolic steroids, thyroid and growth hormone, and diuretics. Neurological examinations revealed symmetrical flaccid paralysis in his lower extremities, but the patient was alert and his sensory system was intact. His initial serum potassium and phosphate level was 1.8 mmol/L and 1.4 mg/dL, respectively. The calculated transtubular potassium gradient (TTKG) was 2.02. His thyroid function was normal. INTERVENTIONS AND OUTCOMES: Serum potassium levels increased to 3.8 mmol/L with intravenous infusion of about 50 mmol of potassium chloride over 20 hours. OUTCOMES: His muscular symptoms improved progressively and he was discharged from the hospital 7 days after admission on foot. He was followed in our outpatient clinic, without recurrence. LESSONS: Physicians should keep in mind that large intakes of food during short periods can provoke hypokalemic paralysis and rhabdomyolysis, especially in bodybuilders. PMID- 28984785 TI - Intestinal Fatty Acid Binding Protein and Citrulline as Markers of Gut Injury and Prognosis in Patients With Acute Pancreatitis. AB - OBJECTIVES: Severe acute pancreatitis (AP) is associated with high mortality due to systemic inflammatory response syndrome in the early phase and secondary infection in the later phase. Concomitant intestinal ischemia often results in gut injury. We studied intestinal fatty acid binding protein (IFABP) and citrulline levels as markers of gut injury to predict prognosis in AP. METHODS: Acute pancreatitis patients at admission and controls were studied. Serum IFABP was measured by enzyme-linked immunosorbent assay and plasma citrulline by high performance liquid chromatography technique. Ultrastructural changes in duodenal biopsy were also compared between the 2 groups. RESULTS: The IFABP concentration was significantly higher in AP cases (n = 94) compared with controls (n = 100) (mean [standard deviation], 592.5 [753.6] vs 87.8 [67.6] pg/mL; P < 0.001) and in patients with severe AP versus mild AP (738.3 [955.3] vs 404.0 [263.3] pg/ mL, P = 0.03). Citrulline concentration was lower in AP versus controls (29.9 [33.8] vs 83.9 [60.1] MUg/L, P < 0.001). We propose a model by which these biomarkers (IFABP >350 pg/mL and citrulline <18 MUg/L) are able to predict poor prognosis in 33.9% of patients with AP. The gut injury was also validated via ultrastructural changes. CONCLUSIONS: Intestinal fatty acid binding protein is a promising prognostic marker in acute pancreatitis. PMID- 28984786 TI - Clinically Significant Differences in Ki-67 Proliferation Index Between Primary and Metastases in Resected Pancreatic Neuroendocrine Tumors. AB - OBJECTIVE: Pancreatic neuroendocrine tumors (NETs) (pNETs) have a varied prognosis according to their grade. The European Neuroendocrine Tumor Society grading system uses assessment of the proliferation index via Ki-67 immunohistochemistry to aid prognosis. There is evidence that the proliferation index can vary significantly within a single tumor, but it is not fully understood to what extent heterogeneity occurs between the primary and metastatic sites and how this may affect the grade. The aim of this study is to determine whether the grade assigned to a pNET varies depending on which site is selected for Ki-67 immunolabeling. METHODS: Patients were selected from our institution's NET database. Patients were included if they had a confirmed pNETs, had multiple resection specimens, and had consented to research being performed on their specimens. Ki-67 immunohistochemistry was performed on all resected specimens meeting the inclusion criteria. RESULTS: Pancreatic neuroendocrine tumors specimens resected from 16 patients were analyzed. There was no trend to higher Ki-67 in metastatic than primary disease. Ki-67 was on average 3% higher in liver metastases than lymph node metastases (P < 0.001). CONCLUSIONS: The grade of pNETs varies according to the tumor selected for Ki-67 immunolabeling. Useful information can be gained by performing Ki-67 PI on liver metastases. PMID- 28984787 TI - Effects of omega-3 Fatty Acids on Toll-like Receptor 4 and Nuclear Factor kappaB p56 in the Pancreas of Rats With Severe Acute Pancreatitis. AB - OBJECTIVES: The aims of this study were to determine the effects of omega-3 fatty acids (omega-3FAs) on the Toll-like receptor 4 (TLR4)/nuclear factor kappaB p56 (NF-kappaBp56) signaling pathway in the pancreas of rats with severe acute pancreatitis (SAP). METHODS: Sixty-four Sprague-Dawley rats were randomly divided into 4 groups: the control, SAP-saline, SAP-soybean oil, and SAP-omega-FA groups. Severe acute pancreatitis was induced by the retrograde infusion of sodium taurocholate into the pancreatic duct. The expression of TLR4 and NF-kappaBp56 in the pancreas was evaluated by immunohistochemistry and Western blot analysis. The levels of the proinflammatory cytokines interleukin 6 and tumor necrosis factor alpha in the pancreas were measured by enzyme-linked immunosorbent assays. RESULTS: Toll-like receptor 4, NF-kappaBp56, and inflammatory cytokine expression in the pancreas was increased significantly in the SAP group compared with that in the control group (P < 0.05), but was significantly decreased in the omega-3FA group compared with that in the soybean oil group at 24 and 48 hours (P < 0.05). CONCLUSIONS: Our results suggest that during the initial stage of SAP omega-3FAs could efficiently lower the inflammatory response by activating the TLR4/NF kappaBp56 signaling pathway. PMID- 28984788 TI - Concurrent Diabetic Ketoacidosis in Hypertriglyceridemia-Induced Pancreatitis: How Does It Affect the Clinical Course and Severity Scores? AB - OBJECTIVES: Concurrent diabetic ketoacidosis (DKA) is highly prevalent in patients with hypertriglyceridemia-induced pancreatitis (HP). Diabetic ketoacidosis could potentially complicate the diagnosis, management, and prognosis of HP. This study aimed to directly compare the clinical course of HP with and without DKA and assess the outcomes of frequently used severity prediction scores in such population. METHODS: We retrospectively analyzed 140 patients with HP; 37 patients (26.4%) had concurrent DKA. We compared epidemiologic characteristics, initial laboratory values, and clinical courses between the DKA and non-DKA groups. Bedside Index for Severity in Acute Pancreatitis score, Sequential Organ Failure Assessment score, Ranson criteria, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and Marshall score were calculated and compared between groups. RESULTS: We observed more acute kidney injury in the DKA group. Patients with DKA more likely required intensive care unit admission, received intravenous insulin, and were discharged on subcutaneous insulin. Ranson criteria and APACHE II score were significantly higher with DKA. CONCLUSIONS: Concurrent DKA does not affect length of stay, in hospital mortality, and readmission rate in patients with HP. Higher Ranson criteria and APACHE II score likely reflected derangement of clinical parameters secondary to DKA rather than true severity of pancreatitis in such population. PMID- 28984790 TI - Different Clinical Characteristics Between Distal Cholangiocarcinoma and Pancreatic Head Carcinoma With Biliary Obstruction. AB - OBJECTIVES: The aim of this study was to compare the perioperative clinical characteristics between patients with distal cholangiocarcinoma (DCC) and pancreatic head carcinoma (PHC) with biliary obstruction. METHODS: This study included patients who underwent pancreatoduodenectomy and were diagnosed with DCC (n = 85) or PHC (n = 90) by final pathological examination. Perioperative clinical characteristics were compared for patients with DCC versus PHC with biliary obstruction. RESULTS: Median coronal thickness of the pancreatic neck was significantly greater, whereas the main pancreatic duct diameter was significantly smaller in patients with DCC than patients with PHC. Most patients with DCC (95%) had a soft pancreas, whereas only 29% of patients with PHC had. The incidence rates of overall morbidity, infectious complications, and pancreatic fistula were significantly higher in patients with DCC than those in patients with PHC. Eleven DCC patients (12%) were preoperatively misdiagnosed with PHC. Among them, intraductal ultrasonography of the bile duct was performed in 7 patients, and the presence of PHC was suspected in 3 of these patients because intraductal ultrasonography detected a small intrapancreatic mass. CONCLUSIONS: This study clearly showed different perioperative characteristics between patients with DCC and PHC. It is not uncommon to misdiagnose PHC as DCC. Intraductal ultrasonography may be helpful in differentiating DCC and PHC. PMID- 28984789 TI - S100P in Duodenal Fluid Is a Useful Diagnostic Marker for Pancreatic Ductal Adenocarcinoma. AB - OBJECTIVES: The development of an effective screening method for pancreatic ductal adenocarcinoma (PDAC) is of paramount importance. This study assessed the diagnostic utility in pancreatic diseases of duodenal markers during upper gastrointestinal endoscopy (GIE) or endoscopic ultrasonography. METHODS: This study prospectively enrolled 299 consecutive participants, including 94 patients with PDACs, 144 patients with other pancreatic diseases, and 61 normal individuals as control subjects. All subjects underwent upper GIE or endoscopic ultrasonography either at Kyushu University Hospital (Fukuoka, Japan) or the Mayo Clinic (Jacksonville, Fla) from October 2011 to July 2014. Duodenal fluid (DF) was collected without secretin stimulation and of carcinoembryonic antigen and S100 calcium-binding protein P (S100P) concentrations were measured. RESULTS: Concentrations of S100P in DF were significantly higher in patients with PDAC and chronic pancreatitis than in control subjects (P < 0.01). A logistic regression model that included age found that the sensitivity and specificity of S100P concentration in diagnosing stages 0/IA/IB/IIA PDAC were 85% and 77%, respectively, with an area under the receiver operating characteristic curve of 0.82. Carcinoembryonic antigen concentrations in DF of patients with pancreatic disease did not differ significantly from control subjects. CONCLUSIONS: Analysis of S100P concentration in DF, in combination with routine screening upper GIE, may facilitate the detection of PDAC. PMID- 28984791 TI - Sex Determining Region Y Box 9 Induces Chemoresistance in Pancreatic Cancer Cells by Induction of Putative Cancer Stem Cell Characteristics and Its High Expression Predicts Poor Prognosis. AB - OBJECTIVES: Pancreatic cancer is a highly chemoresistant tumor and underlying mechanisms are not well understood. Sex determining region Y box 9 (Sox9) is a transcription factor playing important roles on maintenance of pluripotent cells during pancreatic organogenesis. The purpose of this study is to evaluate the roles of Sox9 in pancreatic cancer. METHODS: The Sox9 expression was evaluated by immunohistochemical analysis. Effects of Sox9 inhibition by siRNA or shRNA on chemosensitivity, sphere formation, stem cell markers expression, and in vivo tumor formation rate were examined using pancreatic cancer cell lines. RESULTS: High expression of Sox9 in pancreatic cancer tissue is correlated with poor prognosis (P = 0.011). Cells with high Sox9 expression (PANC-1, Capan-1) showed stronger chemoresistance to Gemcitabine than cells with low Sox9 expression (BxPC 3, MIA PaCa-2). The chemosensitivity in PANC-1 was recovered by suppressing Sox9 using siRNA (P < 0.05). Both sphere formation rate and the proportion of CD44CD24 cells were decreased by Sox9 inhibition. Tumor formation rate of Tet-on inducible Sox9 shRNA-transfected PANC-1 cells in KSN/Slc nude mice was decreased by induction of shRNA with doxycycline feeding (P < 0.05). CONCLUSION: Sox9 plays an important role in chemoresistance by the induction of stemness in pancreatic cancer cells. PMID- 28984792 TI - Effects of Ghrelin miRNA on Inflammation and Calcium Pathway in Pancreatic Acinar Cells of Acute Pancreatitis. AB - OBJECTIVES: The study investigated the effects of endogenous targeted inhibition of ghrelin gene on inflammation and calcium pathway in an in vitro pancreatic acinar cell model of acute pancreatitis. METHODS: Lentiviral expression vector against ghrelin gene was constructed and transfected into AR42J cells. The mRNA and protein expression of each gene were detected by reverse transcription polymerase chain reaction, Western blotting, or enzyme-linked immunosorbent assay. The concentration of intracellular calcium ([Ca]i) was determined by calcium fluorescence mark probe combined with laser scanning confocal microscopy. RESULTS: Compared with the control group, cerulein could upregulate mRNA and protein expression of inflammatory factors, calcium pathway, ghrelin, and [Ca]i. mRNA and protein expression of inflammatory factors increased significantly in cells transfected with ghrelin miRNA compared with the other groups. Intracellular calcium and expression of some calcium pathway proteins decreased significantly in cells transfected with ghrelin miRNA compared with the other groups. CONCLUSIONS: Targeted inhibition of ghrelin gene in pancreatic acinar cells of acute pancreatitis can upregulate the expression of the intracellular inflammatory factors and alleviate the intracellular calcium overload. PMID- 28984793 TI - SPINK1 Gene is Significantly Associated With Pancreatitis: A Comprehensive Meta Analysis. AB - OBJECTIVES: This research was applied to case-control studies of the association between pancreatitis and SPINK1 gene to assess the joint evidence for the association, the influence of individual studies, and evidence for publication bias. METHODS: MEDLINE and Embase were searched to identify longitudinal studies evaluating pancreatitis and SPINK1. Odds ratios (ORs) and 95% confidence interval (CI) were pooled using random-effect models and calculated using Carlin method. Publication bias was assessed using Egger et al's approach (A famous statistic method by Egger et al). Sensitivity, heterogeneity, and trim and fill analyses were conducted. RESULTS: Based on the results, we found that (1) the results support for the association between pancreatitis and SPINK1, when analyzed totally and by subdivision (total [OR, 7.771; 95% CI, 5.232-11.543; P < 0.000]; European [OR,6.400; 95% CI, 4.346-9.426; P < 0.000]; Asian [OR, 11.823; 95% CI, 4.612-30.310; P < 0.000]; American [OR, 3.777; 95% CI, 1.596-8.939; P = 0.002]; mixed: [OR, 13.566; 95% CI, 2.322-79.252, P = 0.004]); (2) no evidence indicates that this association is accounted for by any one study, and no evidence indicates any publication bias exists. CONCLUSIONS: The results indicated that SPINK1 gene, particularly the N34S mutation, has a genetic association with the development of pancreatitis. PMID- 28984794 TI - The use of povidone-iodine in ophthalmology. AB - PURPOSE OF REVIEW: Povidone-iodine (PVI) is a disinfectant and antiseptic agent used for preoperative preparation of the skin and mucous membranes, as well as for the treatment of contaminated wounds. Currently regimens for prophylaxis against postsurgical endophthalmitis are being modified, including a total withdrawal of antibiotics in intravitreal injections. The aim of this study was to evaluate the use of PVI in ophthalmology. RECENT FINDINGS: As a result of its broad spectrum of microbicidal activity, PVI is routinely used in ophthalmic surgery. However, various protocols are applied worldwide and within different procedures. Additional indications include prophylaxis against ophthalmia neonatorum, acute conjunctivitis, adenoviral conjunctivitis, bacterial keratitis or corneal ulcer, endophthalmitis, giant fornix syndrome, and antimicrobial prophylaxis in patients with Boston type I keratoprosthesis. SUMMARY: Despite the introduction of new antiseptics in surgery, PVI is still the preeminent antiseptic measure in ophthalmology. Its use is economically reasonable. There have been no reports of resistance to PVI or anaphylaxis with topical ophthalmic use. Furthermore, it does not induce resistance or cross-grztance to antibiotics. With these advantages the range of indications for topical use of antibiotics might decrease, with PVI as the sole perioperative antiseptic measure. Additional studies are required to assess the optimal timing, concentration and exposure time within different ophthalmic procedures. PMID- 28984796 TI - Continuous non-invasive haemodynamic monitoring: a beneficial impact on patient outcome is needed to gain 'confidence in the technology'. PMID- 28984795 TI - Re-evaluation of peri-operative cardiac risk (the MET REPAIR study): Study protocol of a prospective, multicentre cohort study sponsored by the European Society of Anaesthesiology. PMID- 28984797 TI - Validation of radial artery-based uncalibrated pulse contour method (PulsioFlex) in critically ill patients: A observational study. AB - BACKGROUND: Because of their simplicity, uncalibrated pulse contour (UPC) methods have been introduced into clinical practice in critical care but are often validated with a femoral arterial waveform. OBJECTIVE: We aimed to test the accuracy of cardiac index (CI) measurements and trending ability from a radial artery with one UPC. DESIGN: An observational study. SETTING: Tertiary care mixed surgical ICU. Data were obtained from April 2015 to July 2016. PATIENTS: We studied 20 critically ill mechanically ventilated patients monitored by UPC (PulsioFlex; Pulsion Medical Systems SE, Feldkirchen, Germany). We used transpulmonary thermodilution (PiCCO2) as a reference. MAIN OUTCOME MEASURES: Bland-Altman-analyses with percentage errors were calculated to assess the accuracy of CI values from radial pulse contour analysis (CIRAD), autocalibration (CIAC) and femoral pulse contour analysis (CIFEM). All were compared with a reference (CITD) at 4-h intervals for 24 h. Trending ability was assessed by polar-plots and four-quadrant-plots. CI is given in l min m. RESULTS: Bland Altman-analyses: for CIRAD, the mean bias was -0.1 with limits of agreement (LOA) of -2.9 to 2.7 and a percentage error of 70%; for CIAC, the mean bias was 0 with LOA -2.8 to 2.7 and a percentage error of 70%; for CIFEM, the mean bias was 0 with LOA -1.2 to 1.2 and a percentage error of 30%, respectively. Polar plots for trending: for CIRAD, the angular bias was 12 degrees with radial LOA of 39 degrees , a polar concordance rate of 73% and a concordance rate of 67% in the four-quadrant-plot; for CIAC, the angular bias was 4 degrees with radial LOA of 41 degrees , polar concordance rate of 79% and a concordance rate of 74% in the four quadrant plot; for CIFEM, the angular bias was -2 degrees with radial LOA of 50 degrees , polar concordance rate of 74% and a concordance rate of 81%. CONCLUSION: In critically ill patients, the PulsioFlex system connected to a radial arterial catheter is inaccurate for CI measurements and does not track changes in CI adequately. We therefore recommend using validated thermodilution techniques for monitoring in the critical care setting. PMID- 28984798 TI - Comparing C-MAC videolaryngoscope with direct laryngoscopy for emergency intubation. PMID- 28984799 TI - Reply to: comparing C-MAC videolaryngoscope with direct laryngoscopy for emergency intubation. PMID- 28984800 TI - Pediatric cancer genetics. AB - PURPOSE OF REVIEW: The current review will focus on the current knowledge of the contribution of both germline and somatic mutations to the development and management of cancer in pediatric patients. RECENT FINDINGS: It has long been thought that genetic mutations in both germline and somatic cells can contribute to the development of cancer in pediatric patients. With the recent advances in genomic technologies, there are now over 500 known cancer predisposition genes. Recent studies have confirmed an 8.5-14% germline mutation rate in cancer predisposition genes in pediatric cancer patients. SUMMARY: The discovery of both germline and somatic cells mutation(s) in pediatric cancer patients not only aids in the management of current disease, but can also have direct implications for future management as well as the medical management of family members. PMID- 28984801 TI - Assessing Cochlear Implant Outcomes in Older Adults Using HERMES: A National Web based Database. AB - OBJECTIVE: Cochlear implant (CI) outcomes research has been largely limited to retrospective or single-institution studies in the United States. The objective is to demonstrate the feasibility of using a novel, national, web-based CI database through evaluating CI outcomes in older adults. STUDY DESIGN: Analysis of a prospective, national, web-based database designed for CI outcome tracking (HERMES; HIPAA-secure, Encrypted, Research Management and Evaluation Solution). SETTING: Multi-centered at 18 private practice and academic US medical centers. PATIENTS: Older (age >=75, n = 47) or younger (age <75, n = 103) adult CI patients (n = 150 total, n = 160 ears). MAIN OUTCOME MEASURE(S): Arizona Biomedical (AzBio), CI usage, postoperative complications. RESULTS: Older adults had slightly lower performance on most recent AzBio (56.0%, n = 26, 12.2 +/- 6.5 mo postoperatively) compared with younger adults (74.0%, n = 52, 12.6 +/- 6.5 mo postoperatively; p < 0.01, Mann-Whitney). However, on multiple regression, age was not a significant predictor of AzBio scores after controlling for sex, hearing loss duration, use, and postoperative follow-up duration. Most recent CI use was similar but significantly different (11.4 h/d in older, n = 24 versus 13.0 in younger, n = 45; p = 0.01). Usage also did not decline over time (p = 0.81 in older versus p = 0.46, in younger). The most common complications were similar (vertigo 25 versus 20%, p = 0.45; tinnitus 4 versus 4%, p = 0.93) in older and younger adults, respectively. CONCLUSION: We demonstrate the feasibility of a novel user-friendly, web-based, national CI database to analyze CI outcomes. Older age was not a significant predictor of AzBio scores after adjusting for multiple factors. Additionally, CI use did not decline over time. PMID- 28984802 TI - Vestibular Function Change in a Vasopressin-Induced Hydrops Model. AB - HYPOTHESIS: A vasopressin-induced endoymphatic hydrops model can represent an acute vertiginous attack in Meniere's disease (MD). BACKGROUND: Previous animal models are not appropriate to evaluate the efficacy of new treatments for hydrops because they cannot represent an acute attack of MD. Recently, a new dynamic model was introduced for acute hydrops exacerbation using the vasopressin type 2 receptor agonist, desmopressin (1-deamino-8-D-Arginine vasopressin, VP); however, resulting changes in vestibular function have not been investigated. METHODS: A total of 37 guinea pigs were used. Two to 4 weeks after surgical ablation of endolymphatic sacs in 33 guinea pigs, acute exacerbation of hydrops was induced by a single VP injection in 18 animals (group A). Next, two VP injections at 1 hour interval were administered to investigate the effect of multiple VP doses on vestibular function in the other 15 animals (group B). In the remaining four animals, VP was injected without surgery for the control group (control). Bidirectional sinusoidal harmonic acceleration (SHA) tests of vestibular function were performed. "Type I response" was defined as when the maximum slow-phase velocity (SPV) during left rotation (toward the operated ear) was lower than that during right rotation (toward the normal ear). In contrast, "Type II response" was defined as when maximum SPV at the left rotation was higher than that at the right rotation. Vestibular symmetry scores were analyzed at baseline and after each of two VP injections given 1 hour apart. RESULTS: Vestibular symmetry scores increased at 1 hour after VP injection in all 18 animals in group A (p < 0.001). Two hours after VP injection, symmetry score decreased to the initial score. Two different types of vestibular response were observed after VP. However, the symmetry scores between type I and II responses were not significantly different (p = 0.173). In all 15 animals of Group B, vestibular asymmetry was sustained over 3 hours when two VP injections were given 1 hour apart. In three of Group B, the type of vestibular response changed from type II response to type I response after the 2nd VP injection; however, no animal demonstrated a shift from type I to type II response. CONCLUSION: VP can transiently induce an acute exacerbation of hydrops and asymmetric vestibular dysfunction in guinea pigs. This model could help in studying new treatments for acute hydrops and in explaining the mechanism of bidirectional nystagmus in MD. PMID- 28984803 TI - Long-term Complications and Surgical Failures After Ossiculoplasty. AB - OBJECTIVE: To study long-term complications after ossiculoplasty. STUDY DESIGN: Case series with chart review. SETTING: Tertiary care referral center otology practice. PATIENTS: One hundred ninety-five patients (18-88 yr of age) undergoing ossiculoplasty with tympanoplasty or tympanomastoidectomy using cartilage tympanic membrane grafts, retrograde mastoidectomy with canal wall reconstruction, or mastoid obliteration techniques between July 1998 and July 2012. The studied patients all had at least 3 years of clinical follow-up. OUTCOME MEASURES: Incidence of long-term complications, including need for revision surgery, need for secondary ventilation tube placement, recurrence of conductive hearing loss (and related etiologies), recurrent cholesteatoma, and delayed graft failure (recurrent tympanic membrane perforation). RESULTS: Long term complications were observed in 10.3% (20/195) of patients. 8.2% (16/195) required revision surgery, 10.2% (17/195) required secondary ventilation tube placement, 3.6% (7/195) experienced recurrence of conductive hearing loss, 4.1% (8/195) had delayed failure of tympanic membrane graft, and 1.5% (3/195) had recurrence of cholesteatoma. Recurrence of conductive hearing loss was caused by the displacement of prosthesis in 3 of 7 patients and extensive scar tissue formation without prosthesis displacement in 4 of 7 patients. Seventy-two percent obtained a postoperative pure-tone average - air-bone gap < 20 dB. Forty-eight percent (93/195) obtained a hearing result worse than expected based on the ossiculoplasty outcome parameter staging index. CONCLUSION: Long-term complications are a significant consideration in all the patients undergoing ossiculoplasty. Our data suggest that tobacco smoking, Eustachian tube dysfunction, and an unexpectedly poor hearing result on the first postoperative audiogram are all important risk factors for the development of significant complications. PMID- 28984804 TI - Pediatric Calvarial Bone Thickness in Patients With and Without Aural Atresia. AB - OBJECTIVE: To compare temporal bone thickness along a three-dimensional arc of potential osseointegrated implant sites for bone-anchored hearing aids in children with and without aural atresia using computed tomographic imaging (CT). STUDY DESIGN: Retrospective case review. SETTING: Tertiary children's hospital. PATIENTS: Children with or without aural atresia aged less than 11 years who had a temporal bone CT. INTERVENTION (S): Calvarial bone volume on CT was rendered in three-dimensional and thickness was reconstructed and measured at up to 12 defined sites along an arc of recommended implant sites. MAIN OUTCOME MEASURE (S): Determining whether a majority of observed potential implant sites have 2, 3, or 4 mm of bone thickness while controlling for age differences and atresia status. RESULTS: A total of 40 atretic (from 34 patients) and 34 control (from 34 patients) temporal bones were compared using CT. Likelihood ratio tests indicated that diagnosis did not have a statistically significant effect on whether patients reached thresholds of 2, 3, or 4 mm at most observed sites (p = 0.781, 0.773, and 0.529, respectively) when adjusting for age. For all children measured, 93% had >50% of measured points greater than or equal to 2 mm thick. CONCLUSION: Most children had greater than 2 mm of temporal bone thickness at >50% of the sites measured regardless of age or atresia diagnosis. The likelihood of reaching 4 mm of thickness at most sites improves with age. In unilateral patients, there was not a significant difference in thickness between affected and unaffected sides. There was also no significant difference in thickness when comparing patients with atresia to those without. PMID- 28984805 TI - A Follow-Up Study on Music and Lexical Tone Perception in Adult Mandarin-Speaking Cochlear Implant Users. AB - OBJECTIVE: The aim was to evaluate the development of music and lexical tone perception in Mandarin-speaking adult cochlear implant (CI) users over a period of 1 year. STUDY DESIGN: Prospective patient series. SETTING: Tertiary hospital and research institute. PATIENTS: Twenty five adult CI users, with ages ranging from 19 to 75 years old, participated in a year-long follow-up evaluation. There were also 40 normal hearing adult subjects who participated as a control group to provide the normal value range. INTERVENTIONS: Musical sounds in cochlear implants (Mu.S.I.C.) test battery was undertaken to evaluate music perception ability. Mandarin Tone Identification in Noise Test (M-TINT) was used to assess lexical tone recognition. The tests for CI users were completed at 1, 3, 6, and 12 months after the CI switch-on. MAIN OUTCOMES MEASURES: Quantitative and statistical analysis of their results from music and tone perception tests. RESULTS: The performance of music perception and tone recognition both demonstrated an overall improvement in outcomes during the entire 1-year follow up process. The increasing trends were obvious in the early period especially in the first 6 months after switch-on. There was a significant improvement in the melody discrimination (p < 0.01), timbre identification (p < 0.001), tone recognition in quiet (p < 0.0001), and in noise (p < 0.0001). CONCLUSIONS: Adult Mandarin-speaking CI users show an increasingly improved performance on music and tone perception during the 1-year follow-up. The improvement was the most prominent in the first 6 months of CI use. It is essential to strengthen the rehabilitation training within the first 6 months. PMID- 28984806 TI - Petrous Apex Cholesterol Granulomas: Outcomes, Complications, and Hearing Results From Surgical and Wait-and-Scan Management. AB - OBJECTIVE: 1. To analyze the surgical outcomes in the management of petrous apex cholesterol granulomas (PACG) with a brief literature review.2. To evaluate the importance of wait-and-scan management option. STUDY DESIGN: Retrospective review. SETTING: Quaternary referral center for otology and skull base surgery. SUBJECTS AND METHODS: Charts of 55 patients with at least 12 months of follow-up were analyzed for demographic, clinical, audiometric, and radiological features. Patients were divided into surgical group (SG) (n = 31) and wait-and-scan (n = 24) (WS) group. Surgical approach was chosen as per hearing status and PACG extension and relation to nearby neurovascular structures and included either drainage by transmastoid-infralabyrinthine approach (TM-IL)/transcanal infracochlear approach (TC-IC) or resection by infratemporal fossa type B approach (ITF-B). The combination of ITF-B with trans-otic (TO) approach or TO approach solely was used in unserviceable hearing cases. Postoperative outcomes and complications were evaluated in SG. RESULTS: Postoperative symptom relief was observed in 24 patients (77.4%). Diplopia and paresthesia recovered in each case and improvement in headache, dizziness, tinnitus, and hearing loss was observed in 87.1% cases. Serviceable hearing was preserved in 24 of 26 cases. Postoperative complication rate was 32.2% including incidences of profound hearing loss, facial nerve paresis, carotid artery injury and intraoperative CSF leaks. Revision surgery was required in 3 (9.6%) cases, after TM-IL approach. CONCLUSION: Surgical drainage is preferable to more aggressive resection procedures, with the latter reserved for recurrent lesions or lesions with severe hearing loss/involvement of critical neurovascular structures. ITF-B approach provides adequate cyst and neurovascular control for resection, while avoiding brain retraction. An initial wait-and-scan approach can be used in most patients where symptoms and imaging justify so. PMID- 28984807 TI - Decline of Low-Frequency Hearing in People With Ski-Slope Hearing Loss; Implications for Electrode Array Insertion. AB - HYPOTHESIS: The decline of low-frequency hearing in people with ski-slope hearing loss varies and might depend on etiology. BACKGROUND: People with ski-sloping hearing loss might benefit from cochlear implantation with preservation of residual hearing. To reduce the risk of losing low-frequency hearing after implantation, the electrode-array can be inserted partially up to the desired frequency. That, however, obstructs electrical stimulation of lower frequencies. To decide between complete or partial insertion, knowledge regarding the natural decline of low-frequency hearing is helpful. METHODS: Patients with at least two ski-slope audiograms over time were selected. We calculated progression at lower frequencies for 320 patients. Etiologies for hearing loss were retrieved from medical records. Progression of hearing loss was analyzed separately for patients with uni- and bilateral hearing losses. Relative progression of hearing loss was obtained by comparing progression to a reference group. RESULTS: Average progression of PTA was 1.73 dB/yr and was not significantly different in the bilateral and unilateral group. Etiologies that did not show significantly more progression compared with the reference group could be identified as single or short-lasting pathologic events, whereas long-lasting conditions had significant more progression of PTA. CONCLUSION: Patients with a ski-slope hearing loss that was caused by a single or short-lasting event have low progression rate and are viable for partial insertion to minimize the risk of damaging residual low frequency hearing. In the absence of such an event, complete insertion should be considered because faster than normal deterioration of low-frequency hearing over time will probably limit the advantage of preservation of residual hearing. PMID- 28984808 TI - Cochlear Dysfunction is not Common in Human Meningioma of the Internal Auditory Canal. AB - HYPOTHESIS: Cochlear dysfunction is not common in human meningioma of the internal auditory canal. BACKGROUND: Meningiomas arising from the cerebellopontine angle and internal auditory canal typically cause hearing loss. Cochlear dysfunction is known to contribute to sensorineural hearing loss induced by vestibular schwannoma, the most common tumor of the internal auditory canal. Detailed cochlear histopathology in meningioma has not been reported. METHODS: Retrospective analysis of cochlear histopathology in five unoperated and five operated meningiomas of the internal auditory canal identified after screening human temporal bone collections from three academic medical centers. RESULTS: While some dysfunction of all analyzed cochlear cell types was identified, a predominant or exclusive loss of hair cells was not observed in any meningioma. Only 14.3% of temporal bones showed significantly more hair cell damage on the side of the tumor when compared with the contralateral ear; cochlear neuronal damage was more prevalent in meningiomas. The incidence of hydrops, perilymphatic precipitate, or endolymphatic precipitate was low. CONCLUSIONS: Substantial cochlear damage in human meningioma of the internal auditory canal is not common. This may explain the anecdotal hearing improvement observed after surgical resection of meningioma. Our findings underline the importance of developing therapeutic strategies to prevent cochlear neuronal degeneration due to tumors of the internal auditory canal. PMID- 28984809 TI - Otology at the Academy of Gondishapur 200-600 CE. AB - OBJECTIVE: To investigate the way in which otology was practiced at the Academy of Gondishapur in ancient Persia from 200 to 600 CE. METHOD: The pertinent literature, using German and English translations of Latin, Greek, Arabic, and Sanskrit documents, was identified and reviewed through the indices of available books and through a PDF search for the following topics: auricle, deaf, deafness, dizziness, ear, hearing, medicine, otitis, pinna, punishment-ear, speech, surgery, vertigo, and voice. RESULTS: The medical school at the Academy of Gondishapur followed the medical and surgical practices of Greece and Rome and, in the 6th century, incorporated those from India as detailed in the Shutra Samhita. This shutra, which originated during the first millennium BCE, detailed many interventions, among which one of the most unusual was the use of a pedicle cheek flap to restore the pinnae. The use of the pedicle flap for pinna restoration appears not have been reported in literature again until 1931, by Jacque Joseph. CONCLUSION: During the period of late antiquity, medical knowledge of both the east and west was preserved and taught in Persia. Among surgical interventions used during the first millennium BCE in India, knowledge of which passed, through the shutra, to the Sasanian Empire in the 6th century CE, was use of the pedicle cheek flap for pinna reconstruction. Even as late as the Renaissance, the pedicle flap was not known to surgeons in the West, and a pedicle flap, though not a cheek flap, was first incorporated into Western medical practice during the 1930s. PMID- 28984810 TI - STRC Deletion is a Frequent Cause of Slight to Moderate Congenital Hearing Impairment in the Czech Republic. AB - OBJECTIVE: This study aimed to clarify the molecular epidemiology of hearing loss by identifying the responsible genes in patients without GJB2 mutations. STUDY DESIGN: Prospective genetic study. SETTING: Tertiary referral hospital. PATIENTS: Fifty one patients with bilateral sensorineural hearing loss, 20 men, and 31 women, mean age 24.9 years, range 3 to 64 years, from 49 families. GJB2 and deltaGJB6-D13S1830 mutations were excluded previously. INTERVENTION: Diagnostic. Sixty-nine genes reported to be causative of hearing loss were analyzed. Sequence capture technology, next-generation sequencing, and multiplex ligation-dependent probe amplification (MLPA) were used. Coverage of STRC was screened in Integrative Genomics Viewer software. MAIN OUTCOME MEASURE: Identification of causal pathogenic mutations in genes related to deafness. RESULTS: Five families (10%) had recessive STRC deletions or mutations. Five unrelated patients (10%) had recessive mutations in TMPRSS3, USH2A, PCDH15, LOXHD1, and MYO15A. Three families (6%) had autosomal dominant mutations in MYO6A, KCNQ4, and SIX1. One family (2%) had an X-linked POU3F4 mutation. Thus, we identified the cause of hearing loss in 28% of the families studied. CONCLUSIONS: Following GJB2, STRC was the second most frequently mutated gene in patients from the Czech Republic with hearing loss. To decrease the cost of testing, we recommend STRC deletion screening with MLPA before next-generation sequencing. The existence of a pseudogene and polymorphic STRC regions can lead to false-positive or false negative results when copy number variation analysis is based on next-generation sequencing data. PMID- 28984811 TI - Dizziness Handicap Inventory Score Is Highly Correlated With Markers of Gait Disturbance. AB - OBJECTIVE: To evaluate the association between Dizziness Handicap Inventory Screening version (DHI-S) score and spatiotemporal gait parameters using SoleSound, a newly developed, inexpensive, portable footwear-based gait analysis system. STUDY DESIGN: Cross-sectional. PATIENTS: One hundred eighteen patients recruited from otology clinic. INTERVENTION(S): Subjects completed the DHI-S survey and four uninterrupted walking laps wearing SoleSound instrumented footwear on a hard, flat surface for 100 m. MAIN OUTCOME MEASURE(S): For each subject, mean and coefficient of variation (CV) of stride length, cadence, walking speed, foot-ground clearance, double-support time, swing period, and stance-to-swing were computed by considering 40 strides of steady-state walking within each lap. Linear regression models were employed to study correlations between these variables and DHI-S scores after adjusting for age, sex, and race/ethnicity. RESULTS: Patients with higher DHI-S score took shorter steps and less steps per minute (-0.017 m and -1.1 steps/min per every four-point increase in DHI-S score, p < 0.05) than patients with a lower DHI-S score, with slower walking speed (-0.025 m/s per every four-point increase in DHI-S score, p < 0.01). Additionally, patients with higher DHI-S scores showed larger variability in all analyzed temporal parameters (+0.1% for CV of cadence, +0.5% for CV of double support period, +0.2% for CV of swing period, and +0.4% for CV of stance to-swing, per every four-point increase in DHI-S score, p < 0.01). CONCLUSION: SoleSound was effective in measuring a wide range of gait parameters. Patients' self-perception of vestibular handicap, as assessed with DHI-S, is associated with deterioration in measurable gait parameters independent of age. PMID- 28984812 TI - Factors associated with diffusely increased renal uptake of Tc-99m diphosphono propanedicarboxylic acid on bone scintigraphy in patients with end-stage renal disease. AB - OBJECTIVE: We aimed to determine the factors contributing toward diffusely increased renal uptake on bone scintigraphy using technetium-99m (Tc-99m) diphosphono-propanedicarboxylic acid (DPD) in patients with end-stage renal disease. PATIENTS AND METHODS: One-hundred and forty-three bone scintigraphies, performed between June 2007 and July 2013, in 135 patients with chronic kidney disease were analyzed retrospectively, including 22 bone scintigraphies (15 patients; eight women; seven men) with glomerular filtration rates less than 15 ml/min/1.73 m. Patients with nephrocalcinosis were excluded. The clinical records of medication and underlying disease were reviewed retrospectively. The presence of renal artery calcification was visually estimated and the Hounsfield unit (HU) of renal parenchyma was measured by abdominal and pelvic nonenhanced computed tomography. RESULTS: Two patients underwent peritoneal dialysis and 13 underwent hemodynamic dialysis. Diffusely increased renal Tc-99m DPD uptake was observed on 15 of 22 (68%) bone scintigraphy images. Laboratory test results were not significantly different between the patients with or without increased renal uptake. A history of inflammatory conditions or antibiotic administration did not correlate with kidney visualization. The significant factor for diffuse renal tracer uptake on multivariate analysis was renal artery calcification (odds ratio: 18.42; 95% confidence interval: 2.01-79.43; P<0.001). The mean HU values were significantly higher in patients with diffuse renal tracer uptake (P=0.04) and renal artery calcification (P=0.02). CONCLUSION: Small renal arteriolar calcification and a higher HU value of renal parenchyma could be associated with diffusely increased renal Tc-99m DPD uptake in patients with end-stage renal disease. PMID- 28984813 TI - Dual-isotope subtraction SPECT-CT in parathyroid localization. AB - OBJECTIVE: The aim of this study was to investigate the accuracy of locating parathyroid adenomas using dual-Isotope subtraction single-photon emission computed tomography-computed tomography (SPECT-CT) in comparison with clinical follow-up and pathology findings from surgery. PATIENTS AND METHODS: A retrospective cohort study of dual-isotope subtraction SPECT-CT was carried out on 224 consecutive patients who were diagnosed with primary hyperparathyroidism. All the patients were injected with 20 MBq of iodine-123-iodide, followed 20 min later by 900 MBq of technetium-99m-sestamibi. Planar neck and chest views and SPECT-CT images were acquired 15 min after administration, followed by an additional planar image set at 2 h to view washout; all images were dual energy. In all, 115 out of 224 of the patients imaged underwent parathyroid surgery. The imaging results were compared with pathology findings when available and, in those who did not undergo surgery, and in some complex cases, with clinical measures after a 2-year clinical follow-up period. FINDINGS: Out of the 224 patients, 135 patients had complete pathology and/or clinical follow-up data and were included in the analysis. The sensitivity of the subtraction SPECT-CT findings was measured to be 95%, with a specificity of 89% for the detection and localization of parathyroid adenomas. The positive predictive value was found to be 97% and the negative predictive value was found to be 83%. The accuracy of the technique was 94% in detecting parathyroid adenoma and 92% in accurate localization. CONCLUSION: Dual-isotope subtraction SPECT-CT imaging has a very high sensitivity and specificity in detecting and locating a parathyroid adenoma, showing that it is a very reliable preoperative imaging technique in primary hyperparathyroidism. PMID- 28984814 TI - Clinical utility of 18F-FDG PET/CT in low 18F-FDG-avidity breast cancer subtypes: comparison with breast US and MRI. AB - OBJECTIVE: The aim of this study was to evaluate the diagnostic performance of fluorine-18-fluorodeoxyglucose (F-FDG) PET/CT in initial axillary lymph node (ALN) staging and tumor recurrence in breast cancer subtypes with low F-FDG avidity in comparison with breast ultrasonography (US) and/or MRI. PATIENTS AND METHODS: A total of 491 PET/CT exams from 192 patients with biopsy-proven breast cancer subtypes with low F-FDG avidity were enrolled retrospectively. Nodal status on staging and locoregional recurrence or metastasis on surveillance was confirmed either by pathology or by further clinical follow-up. Comparison was made with recent US and/or MRI. RESULTS: A total of 142 scans were for staging and 349 scans were for surveillance. For the staging, 127 tumors had perceptible F-FDG uptake. For the detection of ALN metastasis, the sensitivity, specificity, and accuracy were calculated to be 51.5, 94.6, and 84.7% for F-FDG PET/CT, 42.4, 90.1, and 79.2% for US, and 51.5, 88.3, and 79.9% for MRI, respectively. PET/CT showed significantly higher specificity than MRI. In the surveillance, the total recurrence rate was 4.3%. There were no cases of recurrence of mucinous or tubular carcinoma. PET/CT showed comparable diagnostic performance for locoregional recurrence compared with US in invasive lobular carcinoma. Distant metastasis developed in five patients (one stage II, four stage III), and all of these were identified by PET/CT alone. CONCLUSION: PET/CT showed comparable diagnostic performance with US and/or MRI for ALN staging and detecting tumor recurrence even when the primary breast cancer has low F-FDG avidity. F-FDG PET/CT also detected unsuspected distant metastasis in 36.4% of stage III patients. Surveillance PET/CT should be considered in advanced-stage invasive lobular carcinoma for early detection of recurrence. PMID- 28984815 TI - Benefits of respiratory-gated 18F-FDG PET acquisition in lung disease. AB - BACKGROUND: Fluorine-18-fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) is a reliable imaging modality for the diagnosis of malignant lung nodules and to assess the latter's prognosis. However, physiological respiratory motion deteriorates PET images and thus decreases the technique's diagnostic and prognostic values. This issue can be overcome by applying respiratory gating to the F-FDG PET/CT acquisitions. PURPOSE: The aim of this study was to evaluate the ability of respiratory-gated F-FDG PET/CT to diagnose malignant lung nodules and to predict recurrence and patient survival. PATIENTS AND METHODS: A total of 103 prospectively enrolled patients with solid lung nodules underwent both ungated and gated F-FDG PET/CT acquisitions. The maximum standardized uptake value (SUVmax) was used to differentiate benign from malignant nodules. Patients have been followed up for at least 36 months to confirm imaging results and assess survival. RESULTS: Gated F-FDG PET/CT was significantly more sensitive than ungated PET/CT for the diagnosis of malignant lung nodules located in the lower lobes (92 vs. 58%; P<0.001) and in patients aged older than 60 years (73 vs. 48%; P<0.001). The same gain was observed for stage I cancers with tumors from 10 to 20 mm. When considering patients aged older than 60 years, those with a low SUVmax on gated PET images had a significantly higher 3-year disease-free survival rate than those with a high SUVmax (76 vs. 47%; P=0.03). CONCLUSION: F FDG PET/CT is advisable for the assessment of lung nodules in patients aged older than 60 years and/or in the lower lobes. PMID- 28984816 TI - Reproducibility of differential renal function measurement using technetium-99m ethylenedicysteine dynamic renal scintigraphy: a French prospective multicentre study. AB - OBJECTIVE: Dynamic renal scintigraphy remains the gold standard for assessing differential renal function (DRF). Recently, technetium-99m-ethylenedicysteine (Tc-EC) was shown to be valuable and had similar quality images as technetium-99m mercaptoacetyltriglycine (Tc-MAG3). However, its reproducibility has never been confirmed. The aim of this study was to perform the first evaluation of Tc-EC reproducibility for assessing DRF in children who were referred for hydronephrosis or urinary tract dilatation. PATIENTS AND METHODS: A total of 109 patients from three French nuclear medicine departments prospectively underwent dynamic renal scintigraphy with Tc-EC. DRF reproducibility was assessed by different pairs of raters using a multilevel design that integrated local and centralized predefined procedures. RESULTS: Both local and centralized procedures yielded near-excellent inter-rater agreements, with all of the intraclass correlation coefficient values over 0.998. Bland-Altman plots showed a systematic bias of less than 1%, with the corresponding limits of agreements not exceeding the 5% threshold cut-off value that corresponds to the clinical definition of acceptable limits for this purpose. Intrarater agreements were also good to excellent. CONCLUSION: This prospective multicentre study showed that Tc-EC is highly reproducible for assessing DRF in a standard paediatric population, thus validating its use as an alternative to Tc-MAG3 in this setting. PMID- 28984817 TI - Robust Weighted Sum Harvested Energy Maximization for SWIPT Cognitive Radio Networks Based on Particle Swarm Optimization. AB - In this paper, we consider multiuser simultaneous wireless information and power transfer (SWIPT) for cognitive radio systems where a secondary transmitter (ST) with an antenna array provides information and energy to multiple single-antenna secondary receivers (SRs) equipped with a power splitting (PS) receiving scheme when multiple primary users (PUs) exist. The main objective of the paper is to maximize weighted sum harvested energy for SRs while satisfying their minimum required signal-to-interference-plus-noise ratio (SINR), the limited transmission power at the ST, and the interference threshold of each PU. For the perfect channel state information (CSI), the optimal beamforming vectors and PS ratios are achieved by the proposed PSO-SDR in which semidefinite relaxation (SDR) and particle swarm optimization (PSO) methods are jointly combined. We prove that SDR always has a rank-1 solution, and is indeed tight. For the imperfect CSI with bounded channel vector errors, the upper bound of weighted sum harvested energy (WSHE) is also obtained through the S-Procedure. Finally, simulation results demonstrate that the proposed PSO-SDR has fast convergence and better performance as compared to the other baseline schemes. PMID- 28984818 TI - Biomass Derived Nitrogen-Doped Highly Porous Carbon Material with a Hierarchical Porous Structure for High-Performance Lithium/Sulfur Batteries. AB - A novel nitrogen doped mesoporous carbon (NMPC) with a hierarchical porous structure is prepared by simple carbonizing the green algae, which is applied as a host material to encapsulate sulfur for lithium/sulfur (Li/S) battery. The NMPC exhibits high pore volume as well as large specific surface area, and thus sulfur content in the S/NMPC composite reaches up to 63 wt %. When tested in a Li/S battery, the S/NMPC composite yields a high initial capacity of 1327 mAh.g-1 as well as 757 mAh.g-1 after 100 cycles at a current rate of 0.1 C, a reversible capacity of 642 was achieved even at 1 C. This good electrochemical performance of the S/NMPC composite could be attributed to a unique combination of mesopority and surface chemistry, allowing for the retention of the intermediate polysuflides within the carbon framework. PMID- 28984819 TI - Unexpected High Intragenomic Variation in Two of Three Major Pest Thrips Species Does Not Affect Ribosomal Internal Transcribed Spacer 2 (ITS2) Utility for Thrips Identification. AB - The mitochondrial cytochrome oxidase I gene (mtCO1) and the ribosomal internal transcribed spacer 2 region (ITS2) are among the most widely used molecular markers for insect taxonomic characterization. Three economically important species of thrips, Scirtothripsdorsalis, Thripspalmi, and Frankliniellaoccidentalis were selected to examine the extent of intragenomic variation within these two marker regions in the family Thripidae, and determine if this variation would affect the utility of markers in thrips molecular diagnostics. For each species, intragenomic (within individual) variation and intergenomic (among individuals) variation was assessed by cloning and sequencing PCR-amplified copies. Intergenomic variation was generally higher than intragenomic variation except in cases where intergenomic variation was very low, as in mtCO1 from S.dorsalis and F.occidentalis. Intragenomic variation was detected in both markers in all three of the thrips species, however, 2-3 times more intragenomic variation was observed for ITS2 than mtCO1 in both S.dorsalis and T.palmi. Furthermore, levels of intragenomic variation were low for both of the genes in F.occidentalis. In all of the three thrips species, no sex-based clustering of haplotypes was observed in either marker. Unexpected high intragenomic variation in ITS2 for two of three thrips species did not interfere with thrips diagnostics. However, caution should be taken in applying ITS2 to certain studies of S.dorsalis and T.palmi when high levels of intragenomic variation could be problematic or confounding. In such studies, mtCO1 may be a preferable marker. Possible reasons for discrepancies in intragenomic variation among genomic regions are discussed. PMID- 28984820 TI - Histopathology of Cervical Cancer and Arsenic Concentration in Well Water: An Ecological Analysis. AB - Arsenic in drinking water is causally linked with cancer of the skin, lung, and urinary bladder, but there is very little data on a possible role for arsenic in the etiology of cervical cancer, a disease in which human papilloma virus is held to be a necessary but not sufficient cause. All histopathology results from cervical specimens from the National Institute of Cancer Research and Hospital (NICRH), Dhaka (1997-2015), and the Anowara Medical Services (2003-2015), both serving the whole of Bangladesh, were classified by cell type. Arsenic concentrations in well water in the thana of residence were estimated from systematic sampling carried out by the British Geological Survey. In a case referent analysis arsenic estimates for cases of cervical cancer were compared with those found to have benign lesions. In this study, 3464 NICRH (CH) cervical specimens and 30,050 community medical service (CMS) specimens were available: 3329 (CH) and 899 (CMS) were recorded as malignant. Most were squamous cell carcinoma, of which 4.9% were poorly differentiated. Overall, there was no increase in cervical cancer with increasing arsenic concentration. Among those with squamous cell histology, a strong dose response was seen for poorly differentiated cancer with increasing arsenic exposure. The odds ratio increased monotonically, compared with exposure <10 MUg/L, from 1.58 at 10 < 50 MUg/L to 8.11 at >200 MUg/L (p < 0.001). Given the high proportion of Bangladeshis using drinking water containing >50 MUg/L of arsenic, the evidence that arsenic is implicated in cancer grade suggests a need for further investigation and the introduction of cervical screening in high arsenic areas. PMID- 28984821 TI - miR-425-5p Inhibits Differentiation and Proliferation in Porcine Intramuscular Preadipocytes. AB - Intramuscular fat (IMF) content affects the tenderness, juiciness, and flavor of pork. An increasing number of studies are focusing on the functions of microRNAs (miRs) during porcine intramuscular preadipocyte development. Previous studies have proved that miR-425-5p was enriched in porcine skeletal muscles and played important roles in multiple physiological processes; however, its functions during intramuscular adipogenesis remain unclear. To explore the role of miR-425 5p in porcine intramuscular adipogenesis, miR-425-5p agomir and inhibitor were used to perform miR-425-5p overexpression and knockdown in intramuscular preadipocytes, respectively. Our results showed that the agomir of miR-425-5p dramatically inhibited intramuscular adipogenic differentiation and downregulated the expression levels of adipogenic marker genes PPARgamma, FABP4, and FASN, whereas its inhibitor promoted adipogenesis. Interestingly, the agomir repressed proliferation of porcine intramuscular preadipocytes by downregulation of cyclin B and cyclin E. Furthermore, we demonstrated that miR-425-5p inhibited adipogenesis via targeting and repressing the translation of KLF13. Taken together, our findings identified that miR-425-5p is a novel inhibitor of porcine intramuscular adipogenesis possibly through targeting KLF13 and subsequently downregulating PPARgamma. PMID- 28984822 TI - A Walnut-Enriched Diet Reduces Lipids in Healthy Caucasian Subjects, Independent of Recommended Macronutrient Replacement and Time Point of Consumption: a Prospective, Randomized, Controlled Trial. AB - : Studies indicate a positive association between walnut intake and improvements in plasma lipids. We evaluated the effect of an isocaloric replacement of macronutrients with walnuts and the time point of consumption on plasma lipids. We included 194 healthy subjects (134 females, age 63 +/- 7 years, BMI 25.1 +/- 4.0 kg/m2) in a randomized, controlled, prospective, cross-over study. Following a nut-free run-in period, subjects were randomized to two diet phases (8 weeks each). Ninety-six subjects first followed a walnut-enriched diet (43 g walnuts/day) and then switched to a nut-free diet. Ninety-eight subjects followed the diets in reverse order. Subjects were also randomized to either reduce carbohydrates (n = 62), fat (n = 65), or both (n = 67) during the walnut diet, and instructed to consume walnuts either as a meal or as a snack. The walnut diet resulted in a significant reduction in fasting cholesterol (walnut vs. CONTROL: 8.5 +/- 37.2 vs. -1.1 +/- 35.4 mg/dL; p = 0.002), non-HDL cholesterol (-10.3 +/- 35.5 vs. -1.4 +/- 33.1 mg/dL; p <= 0.001), LDL-cholesterol (-7.4 +/- 32.4 vs. 1.7 +/- 29.7 mg/dL; p = 0.029), triglycerides (-5.0 +/- 47.5 vs. 3.7 +/- 48.5 mg/dL; p = 0.015) and apoB (-6.7 +/- 22.4 vs. -0.5 +/- 37.7; p <= 0.001), while HDL-cholesterol and lipoprotein (a) did not change significantly. Neither macronutrient replacement nor time point of consumption significantly affected the effect of walnuts on lipids. Thus, 43 g walnuts/d improved the lipid profile independent of the recommended macronutrient replacement and the time point of consumption. PMID- 28984823 TI - Defect Detection and Segmentation Framework for Remote Field Eddy Current Sensor Data. AB - Remote-Field Eddy-Current (RFEC) technology is often used as a Non-Destructive Evaluation (NDE) method to prevent water pipe failures. By analyzing the RFEC data, it is possible to quantify the corrosion present in pipes. Quantifying the corrosion involves detecting defects and extracting their depth and shape. For large sections of pipelines, this can be extremely time-consuming if performed manually. Automated approaches are therefore well motivated. In this article, we propose an automated framework to locate and segment defects in individual pipe segments, starting from raw RFEC measurements taken over large pipelines. The framework relies on a novel feature to robustly detect these defects and a segmentation algorithm applied to the deconvolved RFEC signal. The framework is evaluated using both simulated and real datasets, demonstrating its ability to efficiently segment the shape of corrosion defects. PMID- 28984824 TI - Combined Virtual and Experimental Screening for CK1 Inhibitors Identifies a Modulator of p53 and Reveals Important Aspects of in Silico Screening Performance. AB - A compound collection of pronounced structural diversity was comprehensively screened for inhibitors of the DNA damage-related kinase CK1. The collection was evaluated in vitro. A potent and selective CK1 inhibitor was discovered and its capacity to modulate the endogenous levels of the CK1-regulated tumor suppressor p53 was demonstrated in cancer cell lines. Administration of 10 MUM of the compound resulted in significant increase of p53 levels, reaching almost 2-fold in hepatocellular carcinoma cells. In parallel to experimental screening, two representative and orthogonal in silico screening methodologies were implemented for enabling the retrospective assessment of virtual screening performance on a case-specific basis. Results showed that both techniques performed at an acceptable and fairly comparable level, with a slight advantage of the structure based over the ligand-based approach. However, both approaches demonstrated notable sensitivity upon parameters such as screening template choice and treatment of redundancy in the enumerated compound collection. An effort to combine insight derived by sequential implementation of the two methods afforded poor further improvement of screening performance. Overall, the presented assessment highlights the relation between improper use of enrichment metrics and misleading results, and demonstrates the inherent delicacy of in silico methods, emphasizing the challenging character of virtual screening protocol optimization. PMID- 28984825 TI - Contribution of Drinking Water Softeners to Daily Phosphate Intake in Slovenia. AB - The cumulative phosphate intake in a typical daily diet is high and, according to several studies, already exceeds recommended values. The exposure of the general population to phosphorus via drinking water is generally not known. One of the hidden sources of phosphorus in a daily diet is sodium polyphosphate, commonly used as a drinking water softener. In Slovenia, softening of drinking water is carried out exclusively within the internal (household) drinking water supply systems to prevent the accumulation of limescale. The aim of the study was to determine the prevalence of sodium phosphates in the drinking water in Slovenia in different types of buildings, to determine residents' awareness of the presence of chemical softeners in their drinking water, and to provide an exposure assessment on the phosphorus intake from drinking water. In the current study, the presence of phosphates in the samples of drinking water was determined using a spectrophotometric method with ammonium molybdate. In nearly half of the samples, the presence of phosphates as water softeners was confirmed. The measured concentrations varied substantially from 0.2 mg PO4/L to 24.6 mg PO4/L. Nearly 70% of the respondents were not familiar with the exact data on water softening in their buildings. It follows that concentrations of added phosphates should be controlled and the consumers should be informed of the added chemicals in their drinking water. The health risks of using sodium polyphosphate as a drinking water softener have not been sufficiently investigated and assessed. It is highly recommended that proper guidelines and regulations are developed and introduced to protect human health from adverse effects of chemicals in water intended for human consumption. PMID- 28984826 TI - Binding Affinity of a Highly Sensitive Au/Ag/Au/Chitosan-Graphene Oxide Sensor Based on Direct Detection of Pb2+ and Hg2+ Ions. AB - The study of binding affinity is essential in surface plasmon resonance (SPR) sensing because it allows researchers to quantify the affinity between the analyte and immobilised ligands of an SPR sensor. In this study, we demonstrate the derivation of the binding affinity constant, K, for Pb2+ and Hg2+ ions according to their SPR response using a gold/silver/gold/chitosan-graphene oxide (Au/Ag/Au/CS-GO) sensor for the concentration range of 0.1-5 ppm. The higher affinity of Pb2+ to binding with the CS-GO sensor explains the outstanding sensitivity of 2.05 degrees ppm-1 against 1.66 degrees ppm-1 of Hg2+. The maximum signal-to-noise ratio (SNR) upon detection of Pb2+ is 1.53, and exceeds the suggested logical criterion of an SNR. The Au/Ag/Au/CS-GO SPR sensor also exhibits excellent repeatability in Pb2+ due to the strong bond between its functional groups and this cation. The adsorption data of Pb2+ and Hg2+ on the CS GO sensor fits well with the Langmuir isotherm model where the affinity constant, K, of Pb2+ and Hg2+ ions is computed. The affinity of Pb2+ ions to the Au/Ag/Au/CS-GO sensor is significantly higher than that of Hg2+ based on the value of K, 7 * 105 M-1 and 4 * 105 M-1, respectively. The higher shift in SPR angles due to Pb2+ and Hg2+ compared to Cr3+, Cu2+ and Zn2+ ions also reveals the greater affinity of the CS-GO SPR sensor to them, thus supporting the rationale for obtaining K for these two heavy metals. This study provides a better understanding on the sensing performance of such sensors in detecting heavy metal ions. PMID- 28984827 TI - The Bcl-2 Family in Host-Virus Interactions. AB - Members of the B cell lymphoma-2 (Bcl-2) family are pivotal arbiters of mitochondrially mediated apoptosis, a process of fundamental importance during tissue development, homeostasis, and disease. At the structural and mechanistic level, the mammalian members of the Bcl-2 family are increasingly well understood, with their interplay ultimately deciding the fate of a cell. Dysregulation of Bcl-2-mediated apoptosis underlies a plethora of diseases, and numerous viruses have acquired homologs of Bcl-2 to subvert host cell apoptosis and autophagy to prevent premature death of an infected cell. Here we review the structural biology, interactions, and mechanisms of action of virus-encoded Bcl-2 proteins, and how they impact on host-virus interactions to ultimately enable successful establishment and propagation of viral infections. PMID- 28984829 TI - Potential Toxicity and Underlying Mechanisms Associated with Pulmonary Exposure to Iron Oxide Nanoparticles: Conflicting Literature and Unclear Risk. AB - Fine/micron-sized iron oxide particulates are incidentally released from a number of industrial processes, including iron ore mining, steel processing, welding, and pyrite production. Some research suggests that occupational exposure to these particulates is linked to an increased risk of adverse respiratory outcomes, whereas other studies suggest that iron oxide is biologically benign. Iron oxide nanoparticles (IONPs), which are less than 100 nm in diameter, have recently surged in use as components of novel drug delivery systems, unique imaging protocols, as environmental catalysts, and for incorporation into thermoplastics. However, the adverse outcomes associated with occupational exposure to IONPs remain relatively unknown. Relevant in vivo studies suggest that pulmonary exposure to IONPs may induce inflammation, pulmonary fibrosis, genotoxicity, and extra-pulmonary effects. This correlates well with in vitro studies that utilize relevant dose, cell type(s), and meaningful end points. A majority of these adverse outcomes are attributed to increased oxidative stress, most likely caused by particle internalization, dissolution, release of free iron ions, and disruption of iron homeostasis. However, because the overall toxicity profile of IONPs is not well understood, it is difficult to set safe exposure limit recommendations that would be adequate for the protection of at-risk workers. This review article will focus on known risks following IONPs exposure supported by human, animal, and cell culture-based studies, the potential challenges intrinsic to IONPs toxicity assessment, and how these may contribute to the poorly characterized IONPs toxicity profile. PMID- 28984828 TI - Changes in Dietary Patterns from Childhood to Adolescence and Associated Body Adiposity Status. AB - The aims of this study were to identify cross-sectional dietary patterns (DPs) in a representative sample of 7-10-year-old schoolchildren, to examine how scores for these DPs tracked over a time period of five years (from age 7-10 years to 12 15 years), and to investigate longitudinal associations between changes in DPs scores and changes in BMI (Body Mass Index) z-scores. Children aged 7-10-years were examined in 2007 (n = 1158) and a subset of the sample participated in a follow-up in 2012 (n = 458). Factor analysis (FA) was applied to derive DPs at baseline. The change in DP from childhood to adolescence was analyzed by comparing factor scores using the complete cases, in which factor loadings were the ones evaluated at baseline. Associations of BMI change with DP change were assessed by multivariate linear regression. At baseline, four DP were identified that explained 47.9% of the food intake variance. On average, the factor scores of "DP II" (salty snacks, French fries, fast-food, sugary beverages) decreased in follow-up, while no changes were observed for "DP I" (rice, cooked beans, beef/poultry, leafy vegetables), "DP III" (fruits, cooked and leafy vegetables, fruit juices, pasta, milk, cheese), and "DP IV" (milk, coffee with milk, cheese, breads/biscuits). No significant linear association was shown between changes in BMI z-scores and changes in DP scores from childhood to adolescence. In conclusion, three out of four DP scores identified at baseline tracked slightly in adolescence. PMID- 28984830 TI - Child Community Mental Health Services in Asia Pacific and Singapore's REACH Model. AB - In recent decades, there have been concerted efforts to improve mental health services for youths alongside the challenges of rising healthcare costs and increasing demand for mental health needs. One important phenomenon is the shift from traditional clinic-based care to community-based mental health services to improve accessibility to services and provide patient-centred care. In this article, we discuss the child and adolescent community mental health efforts within the Asia-Pacific region. We also discuss Singapore's community and school based mental health service, known as the Response, Early Intervention and Assessment in Community Mental Health (REACH). This article discusses how REACH has evolved over the years in response to the changing needs of youths in Singapore. Finally, we discuss the current challenges and future directions for youth mental health care. PMID- 28984831 TI - A Theoretical Study of the N to O Linkage Photoisomerization Efficiency in a Series of Ruthenium Mononitrosyl Complexes. AB - Ruthenium nitrosyl complexes are fascinating versatile photoactive molecules that can either undergo NO linkage photoisomerization or NO photorelease. The photochromic response of three ruthenium mononitrosyl complexes, trans [RuCl(NO)(py)4]2+, trans-[RuBr(NO)(py)4]2+, and trans-(Cl,Cl)[RuCl2(NO)(tpy)]+, has been investigated using density functional theory and time-dependent density functional theory. The N to O photoisomerization pathways and absorption properties of the various stable and metastable species have been computed, providing a simple rationalization of the photoconversion trend in this series of complexes. The dramatic decrease of the N to O photoisomerization efficiency going from the first to the last complex is mainly attributed to an increase of the photoproduct absorption at the irradiation wavelength, rather than a change in the photoisomerization pathways. PMID- 28984833 TI - Hydrogen Separation by Natural Zeolite Composite Membranes: Single and Multicomponent Gas Transport. AB - Single and multicomponent gas permeation tests were used to evaluate the performance of metal-supported clinoptilolite membranes. The efficiency of hydrogen separation from lower hydrocarbons (methane, ethane, and ethylene) was studied within the temperature and pressure ranges of 25-600 degrees C and 110 160 kPa, respectively. The hydrogen separation factor was found to reduce noticeably in the gas mixture compared with single gas experiments at 25 degrees C. The difference between the single and multicomponent gas results decreased as the temperature increased to higher than 300 degrees C, which is when the competitive adsorption-diffusion mechanism was replaced by Knudsen diffusion or activated diffusion mechanisms. To evaluate the effect of gas adsorption, the zeolite surface isotherms of each gas in the mixture were obtained from 25 degrees C to 600 degrees C. The results indicated negligible adsorption of individual gases at temperatures higher than 300 degrees C. Increasing the feed pressure resulted in a higher separation efficiency for the individual gases compared with the multicomponent mixture, due to the governing effect of the adsorptive mechanism. This study provides valuable insight into the application of natural zeolites for the separation of hydrogen from a mixture of hydrocarbons. PMID- 28984832 TI - The Role of Omega-3 Fatty Acids in Reverse Cholesterol Transport: A Review. AB - The beneficial effects of omega-3 polyunsaturated fatty acids (n-3 PUFAs) on cardiovascular disease have been studied extensively. However, it remains unclear to what extent n-3 PUFAs may impact Reverse Cholesterol Transport (RCT). RCT describes a mechanism by which excess cholesterol from peripheral tissues is transported to the liver for hepatobiliary excretion, thereby inhibiting foam cell formation and the development of atherosclerosis. The aim of this review is to summarize the literature and to provide an updated overview of the effects of n-3 PUFAs on key players in RCT, including apoliprotein AI (apoA-I), ATP-binding cassette transporter A1 (ABCA1), ABCG1, apoE, scavenger receptor class B type I (SR-BI), cholesteryl ester transfer protein (CETP), low-density lipoprotein receptor (LDLr), cholesterol 7 alpha-hydroxylase (CYP7A1) and ABCG5/G8. Based on current knowledge, we conclude that n-3 PUFAs may beneficially affect RCT, mainly by influencing high-density lipoprotein (HDL) remodeling and by promoting hepatobiliary sterol excretion. PMID- 28984834 TI - Dual Biological Functions of a Cytoprotective Effect and Apoptosis Induction by Bioavailable Marine Carotenoid Fucoxanthinol through Modulation of the Nrf2 Activation in RAW264.7 Macrophage Cells. AB - In this study, the function of fucoxanthinol (FxOH) as a bioavailable marine carotenoid together with the pre-metabolite, fucoxanthin (Fx), was examined through the Nrf2-ARE pathway. The antioxidant activity in the low concentration range of the compounds (1-4 MUM) with a peroxyl radical scavenging capacity was proved by the ORAC (Oxygen Radical Absorbance Capacity) method and an ESR study. Similar concentrations of the compound also activated the Nrf2-ARE signaling with the Nrf2 translocation into the nuclear, then the expression of the antioxidant protein HO-1 increased. On the other hand, the high concentrations of both compounds (>10 MUM) induced apoptosis with caspase 3/7 activation during suppression of the anti-apoptotic proteins, such as Bcl-XL and phosphorous Akt (pAkt). The Nrf2 expression was then activated in the nuclear, indicating that the Nrf2 plays a significant role in the cytoprotective effect against the toxicity of the compounds. These results indicated that the compounds have the dual functions of a cytoprotective effect and the apoptosis induction dependent on the treated concentrations through the Nrf2 activation. In addition, the results of all the assays involved in our previous studies suggested that the metabolite FxOH having a higher activity than the Fx, will be a bioavailable compound in biological systems. PMID- 28984835 TI - Dietary Inflammatory Index and Cardiometabolic Risk Parameters in Overweight and Sedentary Subjects. AB - Nutrition has been established as a relevant factor in the development of cardiovascular disease (CVD). We aimed to investigate the relationship between the dietary inflammatory index (DII) and cardiometabolic risk parameters in a cohort of 90 overweight and sedentary adults from Bogota, Colombia. A 24-h dietary record was used to calculate the DII. Body composition variables, flow mediated dilation (FMD), pulse wave velocity (PWV), lipid profile, glucose, glycosylated hemoglobin (Hb1Ac), and blood pressure were measured and a cardiometabolic risk score (MetScore) was calculated. A lower DII score (anti inflammatory diet) was significantly associated with higher high-density lipoprotein-cholesterol (HDL-C) and FMD, and lower Hb1Ac and MetScore (p < 0.05). A lower DII score was inversely correlated with plasma triglyceride levels (r = 0.354, p < 0.05), glucose (r = -0.422, p < 0.05), MetScore (r = -0.228, p < 0.05), and PWV (r = -0.437, p < 0.05), and positively with FMD (r = 0.261, p < 0.05). In contrast, a higher DII score (pro-inflammatory diet) showed a positive relationship with MetScore (r = 0.410, p < 0.05) and a negative relationship with FMD (r = -0.233, p < 0.05). An increased inflammatory potential of diet was inversely associated with an improved cardiometabolic profile, suggesting the importance of promoting anti-inflammatory diets as an effective strategy for preventing CVD. PMID- 28984836 TI - Balanced Diet-Fed Fat-1 Transgenic Mice Exhibit Lower Hindlimb Suspension-Induced Soleus Muscle Atrophy. AB - The consequences of two-week hindlimb suspension (HS) on skeletal muscle atrophy were investigated in balanced diet-fed Fat-1 transgenic and C57BL/6 wild-type mice. Body composition and gastrocnemius fatty acid composition were measured. Skeletal muscle force, cross-sectional area (CSA), and signaling pathways associated with protein synthesis (protein kinase B, Akt; ribosomal protein S6, S6, eukaryotic translation initiation factor 4E-binding protein 1, 4EBP1; glycogen synthase kinase3-beta, GSK3-beta; and extracellular-signal-regulated kinases 1/2, ERK 1/2) and protein degradation (atrophy gene-1/muscle atrophy F box, atrogin-1/MAFbx and muscle RING finger 1, MuRF1) were evaluated in the soleus muscle. HS decreased soleus muscle wet and dry weights (by 43% and 26%, respectively), muscle isotonic and tetanic force (by 29% and 18%, respectively), CSA of the soleus muscle (by 36%), and soleus muscle fibers (by 45%). Fat-1 transgenic mice had a decrease in the omega-6/omega-3 polyunsaturated fatty acids (PUFAs) ratio as compared with C57BL/6 wild-type mice (56%, p < 0.001). Fat-1 mice had lower soleus muscle dry mass loss (by 10%) and preserved absolute isotonic force (by 17%) and CSA of the soleus muscle (by 28%) after HS as compared with C57BL/6 wild-type mice. p-GSK3B/GSK3B ratio was increased (by 70%) and MuRF-1 content decreased (by 50%) in the soleus muscle of Fat-1 mice after HS. Balanced diet-fed Fat-1 mice are able to preserve in part the soleus muscle mass, absolute isotonic force and CSA of the soleus muscle in a disuse condition. PMID- 28984837 TI - Expression Profiling of Mitogen-Activated Protein Kinase Genes Reveals Their Evolutionary and Functional Diversity in Different Rubber Tree (Hevea brasiliensis) Cultivars. AB - Rubber tree (Heveabrasiliensis) is the only commercially cultivated plant for producing natural rubber, one of the most essential industrial raw materials. Knowledge of the evolutionary and functional characteristics of kinases in H. brasiliensis is limited because of the long growth period and lack of well annotated genome information. Here, we reported mitogen-activated protein kinases in H.brasiliensis (HbMPKs) by manually checking and correcting the rubber tree genome. Of the 20 identified HbMPKs, four members were validated by proteomic data. Protein motif and phylogenetic analyses classified these members into four known groups comprising Thr-Glu-Tyr (TEY) and Thr-Asp-Tyr (TDY) domains, respectively. Evolutionary and syntenic analyses suggested four duplication events: HbMPK3/HbMPK6, HbMPK8/HbMPK9/HbMPK15, HbMPK10/HbMPK12 and HbMPK11/HbMPK16/HbMPK19. Expression profiling of the identified HbMPKs in roots, stems, leaves and latex obtained from three cultivars with different latex yield ability revealed tissue- and variety-expression specificity of HbMPK paralogues. Gene expression patterns under osmotic, oxidative, salt and cold stresses, combined with cis-element distribution analyses, indicated different regulation patterns of HbMPK paralogues. Further, Ka/Ks and Tajima analyses suggested an accelerated evolutionary rate in paralogues HbMPK10/12. These results revealed HbMPKs have diverse functions in natural rubber biosynthesis, and highlighted the potential possibility of using MPKs to improve stress tolerance in future rubber tree breeding. PMID- 28984838 TI - Application of Negative Curvature Hollow-Core Fiber in an Optical Fiber Sensor Setup for Multiphoton Spectroscopy. AB - In this paper, an application of negative curvature hollow core fiber (NCHCF) in an all-fiber, multiphoton fluorescence sensor setup is presented. The dispersion parameter (D) of this fiber does not exceed the value of 5 ps/nm * km across the optical spectrum of (680-750) nm, making it well suited for the purpose of multiphoton excitation of biological fluorophores. Employing 1.5 m of this fiber in a simple, all-fiber sensor setup allows us to perform multiphoton experiments without any dispersion compensation methods. Multiphoton excitation of nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) with this fiber shows a 6- and 9-fold increase, respectively, in the total fluorescence signal collected when compared with the commercial solution in the form of a hollow-core photonic band gap fiber (HCPBF). To the author's best knowledge, this is the first time an NCHCF was used in an optical-fiber sensor setup for multiphoton fluorescence experiments. PMID- 28984839 TI - Complete Mitochondrial Genome Sequencing of a Burial from a Romano-Christian Cemetery in the Dakhleh Oasis, Egypt: Preliminary Indications. AB - The curse of ancient Egyptian DNA was lifted by a recent study which sequenced the mitochondrial genomes (mtGenome) of 90 ancient Egyptians from the archaeological site of Abusir el-Meleq. Surprisingly, these ancient inhabitants were more closely related to those from the Near East than to contemporary Egyptians. It has been accepted that the timeless highway of the Nile River seeded Egypt with African genetic influence, well before pre-Dynastic times. Here we report on the successful recovery and analysis of the complete mtGenome from a burial recovered from a remote Romano-Christian cemetery, Kellis 2 (K2). K2 serviced the ancient municipality of Kellis, a village located in the Dakhleh Oasis in the southwest desert in Egypt. The data were obtained by high throughput sequencing (HTS) performed independently at two ancient DNA facilities (Armed Forces DNA Identification Laboratory, Dover, DE, USA and Carl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, IL, USA). These efforts produced concordant haplotypes representing a U1a1a haplogroup lineage. This result indicates that Near Eastern maternal influence previously identified at Abusir el-Meleq was also present further south, in ancient Kellis during the Romano-Christian period. PMID- 28984841 TI - Can Intensity-Modulated-Radiotherapy Reduce Toxicity in Head and Neck Squamous Cell Carcinoma? AB - Intensity modulated radiotherapy (IMRT) is a modern radiotherapy technique that was implemented in the mid-1990s. It allows closer shaping of dose, to target volumes, thereby sparing organs at risk (OARs). Before the IMRT-era, two dimensional radiotherapy (2DRT) and later three-dimensional conformal radiotherapy (3DCRT) were the techniques of choice, but this robust way of irradiating caused more normal tissue to receive a higher dose. Radiation of cancers in the head and neck region is complex because of close proximity to critical normal tissue and the large target volumes that need to be treated at high doses. IMRT offers an elegant solution compared with 3DCRT and surgery because it allows organ preservation and improved function preservation. In this manuscript, we review the rationales for IMRT, with an emphasis on toxicity outcomes compared with 3DCRT. We performed a review of the literature and looked at the most important randomised controlled trials comparing IMRT with 3DCRT. We conclude that IMRT is safe in regard to disease outcome, and that it allows better sparing of normal tissue, thereby causing less toxicity, resulting in a smaller impact on quality of life compared with conventional radiotherapy in the treatment of head and neck cancer. PMID- 28984840 TI - A Novel and Native Microcystin-Degrading Bacterium of Sphingopyxis sp. Isolated from Lake Taihu. AB - A native, highly efficient microcystin-LR (MC-LR)-degrading bacterium named a7 was isolated from Lake Taihu and identified as Sphingopyxis sp. by 16S rDNA sequence analysis. The strain a7 could totally degrade MC-LR at a rate of 3.33 mg/(L*h), as detected by high-performance liquid chromatography (HPLC). The mlrA, mlrC, and mlrD genes were detected in the strain a7 by sequence analysis. Tetrapeptide and Adda-which are the middle metabolites of MC-LR-were analyzed via liquid chromatography time-of-flight mass spectrometry (LC-TOF-MS) during degradation. These metabolites were degraded completely, which suggested that the native Sphingopyxis sp. a7 was highly efficient in MC-LR degradation under bench conditions. Thus, strain a7 exhibited a significant potential application for bioremediation in water bodies contaminated by MC-LR produced by harmful cyanobacterial blooms. PMID- 28984842 TI - Intercompartmental Piecewise Gene Transfer. AB - Gene relocation from the residual genomes of organelles to the nuclear genome still continues, although as a scaled down evolutionary phenomenon, limited in occurrence mostly to protists (sensu lato) and land plants. During this process, the structural integrity of transferred genes is usually preserved. However, the relocation of mitochondrial genes that code for respiratory chain and ribosomal proteins is sometimes associated with their fragmentation into two complementary genes. Herein, this review compiles cases of piecewise gene transfer from the mitochondria to the nucleus, and discusses hypothesized mechanistic links between the fission and relocation of those genes. PMID- 28984844 TI - Maternal obesity heritably perturbs offspring metabolism for three generations without serial programming. AB - Maternal obesity can program offspring metabolism across multiple generations. It is not known whether multigenerational effects reflect true inheritance of the induced phenotype, or are due to serial propagation of the phenotype through repeated exposure to a compromised gestational milieu. Here we sought to distinguish these possibilities, using the Avy mouse model of maternal obesity. In this model, F1 sons of obese dams display a predisposition to hepatic insulin resistance, which remains latent unless the offspring are challenged with a Western diet. We find that F2 grandsons and F3 great grandsons of obese dams also carry the latent predisposition to metabolic dysfunction, but remain metabolically normal on a healthy diet. Given that the breeding animals giving rise to F2 and F3 were maintained on a healthy diet, the latency of the phenotype permits exclusion of serial programming; we also confirmed that F1 females remained metabolically healthy during pregnancy. Molecular analyses of male descendants identified upregulation of hepatic Apoa4 as a consistent signature of the latent phenotype across all generations. Our results exclude serial programming as a factor in transmission of the metabolic phenotype induced by ancestral maternal obesity, and indicate inheritance through the germline, probably via some form of epigenetic inheritance. PMID- 28984843 TI - Unsupportive parenting moderates the effects of family psychosocial intervention on metabolic syndrome in African American youth. AB - BACKGROUND/OBJECTIVE: Family relationships have been linked to obesity and related disorders in youth, but few studies have provided causal evidence of this association. This study tested the impact of a family psychosocial intervention on components of metabolic syndrome-a condition driven largely by abdominal obesity-in African American youth. In particular, the study tested whether effects were strongest among those who started at highest risk, that is, with high levels of unsupportive parenting at baseline. SUBJECTS/METHODS: Randomized clinical trial of a community sample of 391 African American youth (mean age=11.2 years) conducted in 2001-2002, with follow-up metabolic syndrome assessment in 2014-2015. Participants were assigned either to receive a weekly family intervention or to a control group. The primary study outcome was the number of components of metabolic syndrome that were clinically elevated at age 25, including central adiposity, blood pressure, triglycerides, glucose and low high density lipoproteins. Unsupportive parenting was measured by questionnaires at baseline. RESULTS: Significant interaction effects were found between group assignment and baseline unsupportive parenting on counts of metabolic syndrome components in youth (beta=-0.17, P=0.03). Among those who started with higher levels of unsupportive parenting at age 11, participation in the family intervention reduced the number of clinically elevated components of the metabolic syndrome at age 25 relative to the control group. No such effect was seen among those who started with good parenting. Mediation analyses suggested that changes in the psychosocial targets of the parenting intervention partially accounted for the effects amongst those high in unsupportive parenting at baseline (effect size=-0.350, s.e.=0.178). CONCLUSIONS: These findings suggest that efforts to improve family relationships may be able to ameliorate the detrimental effects that harsh and unsupportive parenting have on obesity-related outcomes such as metabolic syndrome in youth. PMID- 28984845 TI - Site-directed RNA editing by adenosine deaminase acting on RNA for correction of the genetic code in gene therapy. AB - Site-directed RNA editing is an important technique for correcting gene sequences and ultimately tuning protein function. In this study, we engineered the deaminase domain of adenosine deaminase acting on RNA (ADAR1) and the MS2 system to target-specific adenosines, with the goal of correcting G-to-A mutations at the RNA level. For this purpose, the ADAR1 deaminase domain was fused downstream of the RNA-binding protein MS2, which has affinity for the MS2 RNA. To direct editing to specific targets, we designed guide RNAs complementary to target RNAs. The guide RNAs directed the ADAR1 deaminase to the desired editing site, where it converted adenosine to inosine. To provide proof of principle, we used an allele of enhanced green fluorescent protein (EGFP) bearing a mutation at the 58th amino acid (TGG), encoding Trp, into an amber (TAG) or ochre (TAA) stop codon. In HEK 293 cells, our system could convert stop codons to read-through codons, thereby turning on fluorescence. We confirmed the specificity of editing at the DNA level by restriction fragment length polymorphism analysis and sequencing, and at the protein level by western blotting. The editing efficiency of this enzyme system was ~5%. We believe that this system could be used to treat genetic diseases resulting from G-to-A point mutations. PMID- 28984846 TI - Bacteria alone establish the chemical basis of the wood-fall chemosynthetic ecosystem in the deep-sea. AB - Wood-fall ecosystems host chemosynthetic bacteria that use hydrogen sulfide as an electron donor. The production of hydrogen sulfide from decaying wood in the deep sea has long been suspected to rely on the activity of wood-boring bivalves, Xylophaga spp. However, recent mesocosm experiments have shown hydrogen sulfide production in the absence of wood borers. Here, we combined in situ chemical measurements, amplicon sequencing and metagenomics to test whether the presence of Xylophaga spp.-affected hydrogen sulfide production and wood microbial community assemblages. During a short-term experiment conducted in a deep-sea canyon, we found that wood-fall microbial communities could produce hydrogen sulfide in the absence of Xylophaga spp. The presence of wood borers had a strong impact on the microbial community composition on the wood surface but not in the wood centre, where communities were observed to be homogeneous among different samples. When wood borers were excluded, the wood centre community did not have the genetic potential to degrade cellulose or hemicellulose but could use shorter carbohydrates such as sucrose. We conclude that wood centre communities produce fermentation products that can be used by the sulfate-reducing bacteria detected near the wood surface. We thus demonstrate that microorganisms alone could establish the chemical basis essential for the recruitment of chemolithotrophic organisms in deep-sea wood falls. PMID- 28984848 TI - Response to Protocol Review Scenario: Unintended consequences. PMID- 28984847 TI - Mycorrhizal fungi show regular community compositions in natural ecosystems. AB - Dissimilarity overlap curve analysis has shown that 'universality' is a common feature in many complex microbial communities, suggesting that the same taxa interact in a similar manner when shared between communities. We present evidence that arbuscular mycorrhizal fungi, common plant root symbionts, show universal community compositions in natural ecosystems and that this pattern is conserved even at larger spatial scales. However, universality was not detected in agricultural ecosystems potentially implying that agricultural symbiont communities are formed in a different manner. PMID- 28984849 TI - Preparing for a successful infusion study. PMID- 28984850 TI - Smart undershirt. PMID- 28984851 TI - Two major survival surgeries, one protocol: how should the IACUC report violations and change practices? PMID- 28984852 TI - Bio-Serv's Rodent Medicated Dosing Systems (Rodent MD'sTM); a low-stress dosing alternative for rodents during the post-operative period. PMID- 28984853 TI - A minimally invasive method to mend a broken heart. PMID- 28984855 TI - Response to Protocol Review Scenario: Consolidate with caution. PMID- 28984856 TI - All that glitters is gold-frozen fish. PMID- 28984857 TI - Response to Protocol Review Scenario: Oops!... I did it again. PMID- 28984854 TI - Adult zebrafish in CNS disease modeling: a tank that's half-full, not half-empty, and still filling. AB - The zebrafish (Danio rerio) is increasingly used in a broad array of biomedical studies, from cancer research to drug screening. Zebrafish also represent an emerging model organism for studying complex brain diseases. The number of zebrafish neuroscience studies is exponentially growing, significantly outpacing those conducted with rodents or other model organisms. Yet, there is still a substantial amount of resistance in adopting zebrafish as a first-choice model system. Studies of the repertoire of zebrafish neural and behavioral functions continue to reveal new opportunities for understanding the pathobiology of various CNS deficits. Although some of these models are well established in zebrafish, including models for anxiety, depression, and addiction, others are less recognized, for example, models of autism and obsessive-compulsive states. However, mounting data indicate that a wide spectrum of CNS diseases can be modeled in adult zebrafish. Here, we summarize recent findings using zebrafish CNS assays, discuss model limitations and the existing challenges, as well as outline future directions of research in this field. PMID- 28984859 TI - Solving an identity crisis in the taste system. PMID- 28984861 TI - Gnotobiotics: getting a grip on the microbiome boom. PMID- 28984863 TI - Tributes for animals and the dedicated people entrusted with their care: a practical how-to guide. PMID- 28984864 TI - Policy watch: revisions to the Animal Welfare Inspection Guide. PMID- 28984866 TI - Bone marrow stroma cells derived from mononuclear cells at diagnosis as a source of germline control DNA for determination of somatic mutations in acute myeloid leukemia. PMID- 28984865 TI - Malaria in pregnancy: the relevance of animal models for vaccine development. AB - Malaria during pregnancy due to Plasmodium falciparum or P. vivax is a major public health problem in endemic areas, with P. falciparum causing the greatest burden of disease. Increasing resistance of parasites and mosquitoes to existing tools, such as preventive antimalarial treatments and insecticide-treated bed nets respectively, is eroding the partial protection that they offer to pregnant women. Thus, development of effective vaccines against malaria during pregnancy is an urgent priority. Relevant animal models that recapitulate key features of the pathophysiology and immunology of malaria in pregnant women could be used to accelerate vaccine development. This review summarizes available rodent and nonhuman primate models of malaria in pregnancy, and discusses their suitability for studies of biologics intended to prevent or treat malaria in this vulnerable population. PMID- 28984867 TI - Sodium fluoride PET imaging as a quantitative pharmacodynamic biomarker for bone homeostasis during anti-DKK1 therapy for multiple myeloma. PMID- 28984868 TI - A role for caspase-8 and TRAIL-R2/DR5 in ER-stress-induced apoptosis. PMID- 28984869 TI - BCL2 and miR-15/16: from gene discovery to treatment. AB - In 1984, we investigated the t(14;18) chromosomal translocations that frequently occur in patients with follicular lymphoma. We first identified a locus on chromosome 18 involved in these translocations with the chromosome 14 containing the immunoglobulin heavy chain locus. Within this region on chromosome 18, we then discovered a gene that we called BCL2, which was activated by the translocations. Since that time, many studies determined that BCL2 is one of the most important oncogenes involved in cancer by inhibiting apoptosis. In 2002, we studied 13q deletions in chronic lymphocytic leukemia (CLL) and found that the microRNA cluster miR-15a/miR-16-1 (miR-15/16) is deleted by 13q deletions. In 2005, we discovered that miR-15/16 function as tumor suppressors by directly targeting BCL2. Thus the loss of two negative regulators of BCL2 expression results in overexpression of BCL2. Very recently, a specific BCL2 inhibitor ABT 199 (Venetoclax) was developed and approved by FDA for CLL treatment. Thus it took 32 years from fundamental discovery of a critical oncogene to the development of a drug capable to cure CLL. In this review, we discuss the discovery, functions and clinical relevance of miR-15/16 and BCL2. PMID- 28984870 TI - Oxidative stress promotes SIRT1 recruitment to the GADD34/PP1alpha complex to activate its deacetylase function. AB - Phosphorylation of the eukaryotic translation initiation factor, eIF2alpha, by stress-activated protein kinases and dephosphorylation by the growth arrest and DNA damage-inducible protein (GADD34)-containing phosphatase is a central node in the integrated stress response. Mass spectrometry demonstrated GADD34 acetylation at multiple lysines. Substituting K315 and K322 with alanines or glutamines did not impair GADD34's ability to recruit protein phosphatase 1alpha (PP1alpha) or eIF2alpha, suggesting that GADD34 acetylation did not modulate eIF2alpha phosphatase activity. Arsenite (Ars)-induced oxidative stress increased cellular GADD34 levels and enhanced Sirtuin 1 (SIRT1) recruitment to assemble a cytoplasmic complex containing GADD34, PP1alpha, eIF2alpha and SIRT1. Induction of GADD34 in WT MEFs paralleled the dephosphorylation of eIF2alpha (phosphoserine 51) and SIRT1 (phosphoserine-47). By comparison, eIF2alpha and SIRT1 were persistently phosphorylated in Ars-treated GADD34-/- MEFs. Expressing WT GADD34, but not a mutant unable to bind PP1alpha in GADD34-/- MEFs restored both eIF2alpha and SIRT1 dephosphorylation. SIRT1 dephosphorylation increased its deacetylase activity, measured in vitro and in cells. Loss of function of GADD34 or SIRT1 enhanced cellular p-eIF2alpha levels and attenuated cell death following Ars exposure. These results highlighted a novel role for the GADD34/PP1alpha complex in coordinating the dephosphorylation and reactivation of eIF2alpha and SIRT1 to determine cell fate following oxidative stress. PMID- 28984871 TI - How do we fit ferroptosis in the family of regulated cell death? AB - In the last few years many new cell death modalities have been described. To classify different types of cell death, the term 'regulated cell death' was introduced to discriminate it from 'accidental cell death'. Regulated cell death involves the activation of genetically encoded molecular machinery that couples the presence of some signal to cell death. These forms of cell death, like apoptosis, necroptosis and pyroptosis have important physiological roles in development, tissue repair, and immunity. Accidental cell death occurs in response to physical or chemical insults and occurs independently of molecular signalling pathways. Ferroptosis, an emerging and recently (re)discovered type of regulated cell death occurs through Fe(II)-dependent lipid peroxidation when the reduction capacity of a cell is insufficient. Ferroptosis is coined after the requirement for free ferrous iron. Here, we will consider the extent to which ferroptosis is similar to other regulated cell deaths and explore emerging ideas about the physiological role of ferroptosis. PMID- 28984874 TI - Mathematical bias in assessment of placental residual blood volume. PMID- 28984873 TI - RNF20 controls astrocytic differentiation through epigenetic regulation of STAT3 in the developing brain. AB - Astrocyte has crucial roles in the central nervous system and accumulating evidence has shown its core function for brain complexity, plasticity and cognition. However, the essential key factors in the precise regulation of astrocytic differentiation remain largely uncharacterized. Here, we identified that RNF20, an E3 ligase of H2BK120 in the mammalian system, regulates astrocyte production from neural precursor cells. RNF20 deficiency by shRNA knockdown or deletion in conditional knockout mice impairs the astrocytic differentiation. Overexpression of RNF20 promotes astrocytic differentiation and can rescue the astrocyte production deficiency caused by RNF20 disruption. Furthermore, we demonstrate that RNF20 functions cooperatively with acetyltransferase MOF to promote astrocytic generation. RNF20-mediated H2Bub1 cooperating with MOF mediated H4K16ac activates the transcription of Stat3. Together, these data indicate RNF20 is a critical regulator of astrocytic production, which may contribute to the understanding of neurological disorders with glial dysgenesis. PMID- 28984875 TI - Response to Rigo et al. PMID- 28984876 TI - Near infrared spectroscopy and preterm infants-ready for routine use? PMID- 28984877 TI - Approaches to end-of-life discussions with parents of a profoundly compromised newborn. PMID- 28984872 TI - p53 shades of Hippo. AB - The three p53 family members, p53, p63 and p73, are structurally similar and share many biochemical activities. Yet, along with their common fundamental role in protecting genomic fidelity, each has acquired distinct functions related to diverse cell autonomous and non-autonomous processes. Similar to the p53 family, the Hippo signaling pathway impacts a multitude of cellular processes, spanning from cell cycle and metabolism to development and tumor suppression. The core Hippo module consists of the tumor-suppressive MST-LATS kinases and oncogenic transcriptional co-effectors YAP and TAZ. A wealth of accumulated data suggests a complex and delicate regulatory network connecting the p53 and Hippo pathways, in a highly context-specific manner. This generates multiple layers of interaction, ranging from interdependent and collaborative signaling to apparent antagonistic activity. Furthermore, genetic and epigenetic alterations can disrupt this homeostatic network, paving the way to genomic instability and cancer. This strengthens the need to better understand the nuances that control the molecular function of each component and the cross-talk between the different components. Here, we review interactions between the p53 and Hippo pathways within a subset of physiological contexts, focusing on normal stem cells and development, as well as regulation of apoptosis, senescence and metabolism in transformed cells. PMID- 28984878 TI - Efficient electro-optic modulation in low-loss graphene-plasmonic slot waveguides. AB - Surface plasmon polaritons enable light concentration within subwavelength regions, opening thereby new avenues for miniaturizing the device and strengthening light-matter interactions. Here we realize efficient electro-optic modulation in low-loss plasmonic waveguides with the aid of graphene, and the devices are fully integrated in the silicon-on-insulator platform. By advantageously exploiting low-loss plasmonic slot-waveguide modes, which weakly leak into a substrate while featuring strong fields within the two-layer-graphene covered slots in metals, we successfully achieve a tunability of 0.13 dB MUm-1 for our fabricated graphene-plasmonic waveguide devices with extremely low insertion loss, which outperforms previously reported graphene-plasmonic devices. Our results highlight the potential of graphene plasmonic leaky-mode hybrid waveguides to realize active ultra-compact devices for optoelectronic applications. PMID- 28984879 TI - Doping disorder and the reduction-doping process in LiSrPO4. AB - A systematic theoretical study was performed on trivalent and divalent rare-earth (RE) dopant ions in the LiSrPO4 structure, using atomistic simulations based on lattice energy minimization. It was found that RE3+ and RE2+ ions are most energetically favorable for incorporation at the Sr site. For RE3+ ion incorporation, charge compensation by vacancies or anti-site defects are both probable. In order to investigate the reduction-doping process (Europium reduction), two schemes (open atmosphere and H2 reducing atmosphere) were considered. A H2 reduction atmosphere was found to be the most effective agent for Eu reduction. Results reveal that the most probable charge compensation mechanism and the host site preference for rare-earth doping ions play important roles in the investigation of the mechanism of the luminescence properties of LiSrPO4. PMID- 28984880 TI - Low gas permeability of particulate films slows down the aging of gas marbles. AB - Introducing solid particles into liquid films drastically changes their properties: "gas marbles" can resist overpressure and underpressure ten times larger than their pure liquid counterparts - also known as soap bubbles - before deforming. Such gas marbles can therefore prove to be useful as gas containers able to support stresses. Yet, as their liquid counterparts, they can undergo gas transfer, which can reduce the scope of their applications. However, their permeability has never been characterized. In this paper, we measure the gas permeability of gas marbles through dedicated experiments. Our results show that particulate films are less permeable to gas than their pure liquid counterparts. We attribute this limited overall gas flux to the particles that reduce the surface area through which gas diffuses. PMID- 28984881 TI - Polyoxometalate-based gelating networks for entrapment and catalytic decontamination. AB - We report the synthesis and characterization of a new class of organic/inorganic hybrid polymers composed of covalently-bound 1,3,5-benzenetricarboxamide linkers and anionic polyoxovanadate clusters with varying counter-cations. These materials form gels within seconds upon contact with polar aprotic organic liquids and catalyze the degradation of odorants and toxic molecules under mild conditions including aerobic oxidation of thiols, hydrogen peroxide-catalyzed oxidation of sulfides, and hydrolysis of organophosphate chemical warfare agent analogues. PMID- 28984882 TI - Phosphoramidate hydrolysis catalyzed by human histidine triad nucleotide binding protein 1 (hHint1): a cluster-model DFT computational study. AB - As a member of the histidine triad (HIT) protein superfamily, human histidine triad nucleotide binding protein 1 (hHint1) serves as an efficient enzyme in the hydrolysis of phosphoramidate. In particular, hHint1 has been utilized to activate nucleotide prodrugs (proTides). Understanding the mechanism of hHint1 will aid in the future design of proTides. Density functional theory (DFT) computations on a 228-atom cluster active-site model were performed to investigate the hydrolysis mechanism of a phosphoramidate substrate. The overall proposed mechanism included the key involvement of the histidine triad as a proton shuttle. Protonated methylphosphoramidate was first formed by proton transfer of protonated His114 species. A penta-coordinated phosphoryl intermediate, protonated methylphosphorodiamidate, was generated by a nucleophilic attack of His112. After the release of amine and the generation of a phosphorylated histidine intermediate, the nucleophilic attack of an active-site water produced a hydrolyzed intermediate that subsequently transferred a proton back to His114. A rate-determining fully associative pathway with a free energy of activation of 21.7 kcal mol-1 formed the penta-coordinated phosphoryl intermediate. A non-rate determining associative-interchange transition state was involved in the formation of transient tetra-coordinated phosphoryl intermediate. The overall hydrolysis was favorable by -16.1 kcal mol-1. PMID- 28984883 TI - Synthesis of long hierarchical MoS2 nanofibers assembled from nanosheets with an expanded interlayer distance for achieving superb Na-ion storage performance. AB - MoS2 material is considered as a promising anode material candidate in Na-ion batteries (NIBs) due to its high theoretical capacity and layered structure. However, MoS2 nanosheets usually tend to restack or aggregate during the synthesis and cycling process, which makes the advantages of the separated nanosheets disappear. Here, we present a PVP-assisted synthesis for growing long hierarchical MoS2 nanofibers with a length up to 74.5 MUm, which were further assembled from intercrossed curly nanosheets with expanded (002) interlayer spacings in the range of 0.62 nm to 1.14 nm. Such architectural design simultaneously combines multiple-scale structural features that are desired for Na-ion storage. On the one hand, the nanosheets can provide a large surface area which is in contact with the electrolyte, a short Na-ion diffusion pathway from the lateral side and facile Na-ion insertion and extraction through the expanded (002) interlayer; on the other hand, the hierarchical MoS2 nanofibers possess a one dimensional structure and a suitable amount of carbon, which can both serve as an electrical highway and prevent them from restacking, resulting in an enhanced electrochemical performance. When used as an anode in NIBs, they demonstrated excellent cycling performance (537 mA h g-1 at 0.1 A g-1 after 200 cycles, and 370 mA h g-1 at 2 A g-1 over 200 cycles) and outstanding rate capability (329 mA h g-1 at 10 A g-1). PMID- 28984885 TI - Evaluation of mesoporous silica nanoparticles for oral drug delivery - current status and perspective of MSNs drug carriers. AB - The oral pathway is considered as the most common method for drug administration, although many drugs, especially the highly pH- and/or enzymatic biodegradable peptide drugs, are very difficult to formulate and achieve a good intestinal absorption. Efficient systematic absorption of an active substance, delivered via oral ingestion, is only achievable if the drug (1) is substantially present as a solution in the gastrointestinal tract, (2) is able to penetrate through the intestinal mucus, (3) overcomes the different gastrointestinal barriers, and (4) provides an effective therapeutic dose. Therefore, optimization of oral bioavailability of poorly-soluble drugs still remains a significant challenge for the pharmaceutical industry. Even though numerous conventional drug carriers have successfully solved some of the issues related to oral delivery of poorly-soluble drugs, only few of them met commercialization requirements. These drawbacks have led the scientific world to reconsider its approaches toward targeted drug delivery systems and researchers started looking for alternative vectorized carriers. In this area, nanoparticle-based materials have several significant advantages over free and non-formulated drugs. For example, nanosized porous silica carriers allow for more sustained and controlled drug release or improved oral bioavailability. Thus, in the present review, we will highlight the most important features of nanostructured silica drug carriers, such as particle size, particle shape, surface roughness or surface functionalization, and underline the key advantages of these nanosupports. In particular, this article will discuss recent progress and challenges in the area of mesoporous silica nanocarriers used for oral drug delivery. Additional emphasis will be set on the biological and chemical features of the gastrointestinal tract as well as currently tested nanoformulations and strategies to avoid drug degradation in the gastrointestinal environment. PMID- 28984884 TI - Debranchase-resistant labeling of RNA using the 10DM24 deoxyribozyme and fluorescent modified nucleotides. AB - The 10DM24 deoxyribozyme can site-specifically label RNAs with fluorophore-GTP conjugates; however, the 2',5'-branched RNA linkage is readily cleaved by debranchase. To prevent loss of labels upon cleavage, we synthesized phosphorothioate-modified, fluorescent GTP derivatives and elaborated conditions for their incorporation by 10DM24. RNAs labeled with fluorescent derivatives of Sp-GTPS were found to be resistant to debranchase. PMID- 28984886 TI - Copper(i)-catalyzed 5-exo-trig radical cyclization/borylation of alkyl halides: access to functionalized pyrrolidine derivatives. AB - This work reports the copper(i)-catalyzed 5-exo-trig radical cyclization/borylation of alkyl halides bearing an alkene moiety, during which a C-C bond and a C-B bond were formed in one step. Various functionalized pyrrolidine derivatives bearing a quaternary carbon center were obtained, and they showed good functional group tolerance and high chemoselectivity. This transformation was highly efficient and could be finished in 20 minutes. A radical mechanism has been proposed. PMID- 28984887 TI - Size dependence of efficiency of PbS quantum dots in NiO-based dye sensitised solar cells and mechanistic charge transfer investigation. AB - Quantum dots (QDs) are very attractive materials for solar cells due to their high absorption coefficients, size dependence and easy tunability of their optical and electronic properties due to quantum confinement. Particularly interesting are PbS QDs owing to their broad spectral absorption until long wavelengths, their easy processability and low cost. Here, we used control of the PbS QD size to understand charge transfer processes at the interfaces of a NiO semiconductor and explain the optimal QD size in photovoltaic devices. Towards this goal, we have synthesized a series of PbS QDs with different diameters (2.8 nm to 4 nm) and investigated charge transfer dynamics by time resolved spectroscopy and their ability to act as sensitizers in nanocrystalline NiO based solar cells using the cobalt tris(4,4'-ditert-butyl-2,2'-bipyridine) complex as a redox mediator. We found that PbS QDs with an average diameter of 3.0 nm show the highest performance in terms of efficient charge transfer and light harvesting efficiency. Our study showed that hole injection from the PbS QDs to the NiO valence band (VB) is an efficient process even with low injection driving force ( 0.3 eV) and occurs in 6-10 ns. Furthermore we found that direct electrolyte reduction (photoinduced electron transfer to the cobalt redox mediator) also occurs in parallel to the hole injection with a rate constant of similar magnitude (10-20 ns). In spite of its large driving force, the rate constant of the oxidative quenching of PbS by Co(iii) diminishes more steeply than hole injection on NiO when the diameter of PbS increases. This is understood as the consequence of increasing the trap states that limit electron shift. We believe that our detailed findings will advance the future design of QD sensitized photocathodes. PMID- 28984888 TI - Consumption of a single serving of red raspberries per day reduces metabolic syndrome parameters in high-fat fed mice. AB - Using an animal model for diet-induced metabolic disease, we have shown previously that the addition of raspberry juice concentrate (RJC) and raspberry puree concentrate (RPC) at a level of 10% of kcal, equivalent to four servings per day, to an obesogenic high-fat, western-style diet (HF) significantly reduced body weight gain, serum resistin levels, and altered the expression of hepatic genes related to lipid metabolism and oxidative stress. This study was designed to examine the effect of a lower level of RJC or RPC consumption, at a level representing a single serving of food per day (2.5% of kcal). For ten weeks, four groups of C57BL/6J mice (n = 8 ea.) were fed: low fat (LF), HF, HF + RJC, or HF + RPC diets. Intake of RJC and RPC decreased final body weight. Hepatic lipid accumulation was significantly decreased in HF + RPC- and HF + RJC-fed mice, compared to HF-fed mice. Further, the relative expression of hepatic genes including Heme oxygenase 1 (Hmox1) and Hormone sensitive lipase (Lipe), were altered by RPC or RJC consumption. In this mouse model of diet-induced metabolic disease, consumption of the equivalent of a single daily serving of either RPC or RJC improved metabolism in mice fed HF diet. We hypothesize that the phytochemicals contained in raspberries, and/or their subsequent metabolites, may be acting to influence gene expression and other regulatory pathways, to produce the metabolic improvements observed in this study. PMID- 28984889 TI - Investigation of the dynamics of aqueous proline solutions using neutron scattering and molecular dynamics simulations. AB - We applied quasielastic neutron scattering (QENS) techniques to samples with two different contrasts (deuterated solute/hydrogenated solvent and the opposite label) to selectively study the component dynamics of proline/water solutions. Results on diluted and concentrated solutions (31 and 6 water molecules/proline molecule, respectively) were analyzed in terms of the susceptibility and considering a recently proposed model for water dynamics [Arbe et al., Phys. Rev. Lett., 2016, 117, 185501] which includes vibrations and the convolution of localized motions and diffusion. We found that proline molecules not only reduce the average diffusion coefficient of water but also extend the time/frequency range of the crossover region ('cage') between the vibrations and purely diffusive behavior. For the high proline concentration we also found experimental evidence of water heterogeneous dynamics and a distribution of diffusion coefficients. Complementary molecular dynamics simulations show that water molecules start to perform rotational diffusion when they escape the cage regime but before the purely diffusive behavior is established. The rotational diffusion regime is also retarded by the presence of proline molecules. On the other hand, a strong coupling between proline and water diffusive dynamics which persists with decreasing temperature is directly observed using QENS. Not only are the temperature dependences of the diffusion coefficients of both components the same, but their absolute values also approach each other with increasing proline concentration. We compared our results with those reported using other techniques, in particular using dielectric spectroscopy (DS). A simple approach based on molecular hydrodynamics and a molecular treatment of DS allows rationalizing the a priori puzzling inconsistency between QENS and dielectric results regarding the dynamic coupling of the two components. The interpretation proposed is based on general grounds and therefore should be applicable to other biomolecular solutions. PMID- 28984890 TI - Multi-centre study of whole-heart dynamic 3D cardiac magnetic resonance perfusion imaging for the detection of coronary artery disease defined by fractional flow reserve: gender based analysis of diagnostic performance. AB - Aims: Coronary artery disease (CAD) is a leading cause of morbidity and mortality in women and non-invasive testing for CAD in women can be more challenging than in men. This study compared the diagnostic performance of whole-heart dynamic 3D cardiovascular magnetic resonance (CMR) stress perfusion imaging in female and male patients with quantitative coronary angiography (QCA) and fractional flow reserve (FFR) as reference tests. Methods and results: Four hundred sixteen patients with suspected or known CAD were enrolled in five European centres. CMR imaging was performed prior to clinically indicated coronary angiography. QCA was performed in all patients and FFR in 357 of 416 patients. Whole-heart dynamic 3D CMR first-pass perfusion imaging was conducted at rest and during adenosine stress. All CMR analyses were operated by experienced investigators blinded to all clinical data. One hundred nineteen female and 297 male patients were included and successfully examined (mean age 65 +/- 11 and 63 +/- 11 years, respectively). FFR was performed in 106 female and 251 male patients. Sensitivity and specificity of whole-heart dynamic 3D CMR stress perfusion imaging were 89% (95% CI: 77-96) and 82% (95% CI: 70-90) in the female population and 83% (95% CI: 77-86) and 79% (95% CI: 71-86) in the male population relative to QCA (P = 0.474 and P = 0.83, P-values for comparison between genders). Sensitivity and specificity were 95% (95% CI: 82-99) and 84% (95% CI: 73-92) in the female population and 83% (95% CI: 76-89) and 82% (95% CI: 74-88) in the male population when using FFR as the reference (P = 0.134 and P = 0.936, P-values for comparison between genders). Diagnostic accuracy in females was 92% (95% CI: 85-96) and 86% (95% CI: 81-90) in males when using FFR as the reference. The prevalence of CAD as defined by FFR (<0.8) was 36% in females and 53% in males. Conclusion: Whole heart dynamic 3D CMR stress perfusion imaging has a high diagnostic accuracy for the detection of significant CAD irrespective of gender and is therefore a suitable non-invasive testing tool to detect myocardial ischaemia in both genders. PMID- 28984891 TI - Mechanical dyssynchrony-resurrected as a flashing and rocking parameter to predict prognosis after cardiac resynchronization therapy. PMID- 28984892 TI - Overcoming the difficulties to adequately detect myocardial ischaemia in women. PMID- 28984893 TI - The years 2015-2016 in the European Heart Journal-Cardiovascular Imaging. Part I. AB - The multimodality cardiovascular imaging journal, European Heart Journal Cardiovascular Imaging, was launched in 2012. It has gained an impressive impact factor of 5.99 during its 5 first years and is now established as the most important cardiovascular imaging journal in Europe. The most important studies from the journal's forth and fifth years will be highlighted in two reports. Part I of the review will focus on studies about myocardial function and risk prediction, myocardial ischaemia, and emerging techniques in cardiovascular imaging, while Part II will focus on valvular heart disease, heart failure, cardiomyopathies, and congenital heart disease. PMID- 28984894 TI - A joint procedural position statement on imaging in cardiac sarcoidosis: from the Cardiovascular and Inflammation & Infection Committees of the European Association of Nuclear Medicine, the European Association of Cardiovascular Imaging, and the American Society of Nuclear Cardiology. AB - This joint position paper illustrates the role and the correct use of echocardiography, radionuclide imaging with 18F-fluorodeoxyglucose positron emission tomography, radionuclide myocardial perfusion imaging and cardiovascular magnetic resonance imaging for the evaluation and management of patients with known or suspected cardiac sarcoidosis. This position paper will aid in standardizing imaging for cardiac sarcoidosis and may facilitate clinical trials and pooling of multi-centre data on cardiac sarcoidosis. Proposed flow charts for the work up and management of cardiac sarcoidosis are included. PMID- 28984895 TI - New Balance, New Beginning. AB - Following the passage of TMA-supported legislation to loosen maintenance of certification (MOC) requirements, Texas is now a national leader in reducing the onerousness of MOC on physicians. What will the new law do once it takes effect at the beginning of 2018, and what could it do to keep more physicians in practice? PMID- 28984896 TI - Marketing Is Not a Luxury - Marketing Is a Necessity. AB - Physicians who work in small practices constantly face a basic marketing question: What's the best way to sell myself and my business to the community? Because few physicians studied business principles, many won't know the answer. That's why the Texas Medical Association is publishing a book titled Marketing Smart: A Guide for Medical Practices. PMID- 28984897 TI - Don't Get Waste-Deep. AB - The U.S. Environmental Protection Agency and the Texas Commission on Environmental Quality both have roles in regulating waste that physician practices generate, and it's not all about proper handling and disposal. Registration and paperwork negligence can land practices in big trouble as well. PMID- 28984898 TI - QPP Made Simple(r). AB - The Physicians Advocacy Institute is helping doctors understand the MACRA Quality Payment Program (QPP) by launching an online resource center with the help of the Texas Medical Association, other state medical societies, and health care consulting firm Healthsperien. PMID- 28984899 TI - The Problems of Parental Leave. AB - The United States is the only major industrialized country in the world to not require paid parental leave. Numerous studies have shown that allowing parents time with a newborn makes the child and the parents healthier, both physically and mentally. Many physicians, especially those who work in practices with five or fewer doctors, worry about how to pay for parental leave for themselves and their staff. PMID- 28984900 TI - Borrowing Trouble? AB - Education debt is a growing problem that heavily influences which students choose the medical field and discourages many low-income and minority students. PMID- 28984902 TI - Regulation of ICAM-1 and IL-6 in Myocardial Ischemia: Effect of Reperfusion a. PMID- 28984901 TI - Truly selective primary IgM deficiency is probably very rare. AB - Isolated decreased serum-immunoglobulin (Ig)M has been associated with severe and/or recurrent infections, atopy and autoimmunity. However, the reported high prevalence of clinical problems in IgM-deficient patients may reflect the skewed tertiary centre population studied so far. Also, many papers on IgM deficiency have included patients with more abnormalities than simply IgM-deficiency. We studied truly selective primary IgM deficiency according to the diagnostic criteria of the European Society for Immunodeficiencies (ESID) (true sIgMdef) by reviewing the literature (261 patients with primary decreased serum-IgM in 46 papers) and analysing retrospectively all patients with decreased serum-IgM in a large teaching hospital in 's-Hertogenbosch, the Netherlands [1 July 2005-23 March 2016; n = 8049 IgM < 0.4 g/l; n = 2064 solitary (IgG+IgA normal/IgM < age matched reference)]. A total of 359 of 2064 (17%) cases from our cohort had primary isolated decreased serum-IgM, proven persistent in 45 of 359 (13%) cases; their medical charts were reviewed. Our main finding is that true sIgMdef is probably very rare. Only six of 261 (2%) literature cases and three of 45 (7%) cases from our cohort fulfilled the ESID criteria completely; 63 of 261 (24%) literature cases also had other immunological abnormalities and fulfilled the criteria for unclassified antibody deficiencies (unPAD) instead. The diagnosis was often uncertain (possible sIgMdef): data on IgG subclasses and/or vaccination responses were lacking in 192 of 261 (74%) literature cases and 42 of 45 (93%) cases from our cohort. Our results also illustrate the clinical challenge of determining the relevance of a serum sample with decreased IgM; a larger cohort of true sIgMdef patients is needed to explore fully its clinical consequences. The ESID online Registry would be a useful tool for this. PMID- 28984903 TI - Whole genome microarray expression analysis in blood identifies pathways linked to signs and symptoms of a patient with hypercalprotectinaemia and hyperzincaemia. AB - A child, 2 years with the 'hypercalprotectinaemia with hyperzincaemia' clinical syndrome, presented with atypical symptoms and signs, notably persistent fever of approximately 38 degrees C, thrombocythaemia of > 700 * 109 /l and a predominance of persistent intestinal symptoms. In an effort to find a cure by identifying the dysregulated pathways we analysed whole-genome mRNA expression by the Affymetrix HG U133 Plus 2.0 array in blood on three occasions 3-5 months apart. Major up regulation was demonstrated for the Janus kinase/signal transducer and activators of transcription (JAK/STAT) pathway including, in particular, CD177, S100A8, S100A9 and S100A12, accounting for the thrombocytosis; a large number of interleukins, their receptors and activators, accounting for the febrile apathic state; and the high mobility group box 1 (HMBG1) gene, possibly accounting for part of the intestinal symptoms. These results show that gene expression array technology may assist the clinician in the diagnostic work-up of individual patients with suspected syndromal states of unknown origin, and the expression data can guide the selection of optimal treatment directed at the identified target pathways. PMID- 28984904 TI - Vaginal-assisted laparoscopic sacrohysterocervicopexy with retroperitoneal tunneling. PMID- 28984905 TI - Meta-analysis of bipolar radiofrequency endometrial ablation versus thermal balloon endometrial ablation for the treatment of heavy menstrual bleeding. AB - BACKGROUND: Heavy menstrual bleeding is a common problem that can severely affect quality of life. OBJECTIVES: To compare bipolar radiofrequency endometrial ablation and thermal balloon ablation for heavy menstrual bleeding in terms of efficacy and health-related quality of life (HRQoL). SEARCH STRATEGY: Online registries were systematically searched using relevant terms without language restriction from inception to November 24, 2016. SELECTION CRITERIA: Randomized control trials or cohort studies of women with heavy menstrual bleeding comparing the efficacy of two treatments were eligible. DATA COLLECTION AND ANALYSIS: Data were extracted. Results were expressed as risk ratios (RRs) or weighted mean differences (WMDs) with 95% confidence intervals (CIs). MAIN RESULTS: Six studies involving 901 patients were included. Amenorrhea rate at 12 months was significantly higher after bipolar radiofrequency endometrial ablation than after thermal balloon ablation (RR 2.73, 95% CI 2.00-3.73). However, no difference at 12 months was noted for dysmenorrhea (RR 1.04, 95% CI 0.68-1.58) or treatment failure (RR 0.78, 95% CI 0.38-1.60). The only significant difference for HRQoL outcomes was for change in SAQ pleasure score (12 months: WMD -3.51, 95% CI -5.42 to -1.60). CONCLUSIONS: Bipolar radiofrequency endometrial ablation and thermal balloon ablation reduce menstrual loss and improve quality of life. However, bipolar radiofrequency endometrial ablation is more effective in terms of amenorrhea rate and SAQ pleasure. PMID- 28984906 TI - Lateral hypothalamic Orexin-A-ergic projections to the arcuate nucleus modulate gastric function in vivo. AB - It has been well-known that hypothalamic orexigenic neuropeptides, orexin-A, and melanin-concentrating hormone (MCH), play important roles in regulation of gastric function. However, what neural pathway mediated by the two neuropeptides affects the gastric function remains unknown. In this study, by way of nucleic stimulation and extracellular recording of single unit electrophysiological properties, we found that electrically stimulating the lateral hypothalamic area (LH) or microinjection of orexin-A into the arcuate nucleus (ARC) excited most gastric distension-responsive neurons in the nuclei and enhanced the gastric function including motility, emptying, and acid secretion of conscious rats. The results indicated that LH-ARC orexin-A-ergic projections may exist and the orexin A in the ARC affected afferent and efferent signal transmission between ARC and stomach. As expected, combination of retrograde tracing and immunohistochemistry showed that some orexin-A-ergic neurons projected from the LH to the ARC. In addition, microinjection of MCH and its receptor antagonist PMC-3881-PI into the ARC affected the role of orexin-A in the ARC, indicating a possible involvement of the MCH pathway in the orexin-A role. Our findings suggest that there was an orexin-A-ergic pathway between LH and ARC which participated in transmitting information between the central nuclei and the gastrointestinal tract and in regulating the gastric function of rats. PMID- 28984908 TI - Novel Antioxidant Therapy for Cerebral Ischemia-Reperfusion Injury. PMID- 28984907 TI - Prader-Willi syndrome genetic subtypes and clinical neuropsychiatric diagnoses in residential care adults. AB - The historical diagnosis of Prader-Willi syndrome (PWS), a complex genetic disorder, in adults is often achieved by clinical presentation rather than by genetic testing and thus limited genetic subtype-specific psychometric investigations and treatment options. Genetic testing and clinical psychiatric evaluation using Diagnostic and Statistical Manual (DSM)-IV-TR criteria were undertaken on 72 adult residents (34 M; 38 F) from the Prader-Willi Homes of Oconomowoc (PWHO), a specialty PWS group home system. Methylation specific multiplex ligation probe amplification and high-resolution microarrays were analyzed for methylation status, 15q11-q13 deletions and maternal uniparental disomy 15 (mUPD15). Seventy (33M; 37F) of 72 residents were genetically confirmed and 36 (51%) had Type I or Type II deletions; 29 (42%) with mUPD15 and 5 (7%) with imprinting defects from three separate families. Psychiatric comorbidities were classified as anxiety disorder (38%), excoriation (skin picking) (33%), intermittent explosive disorder ([30%-predominantly among males at 45% compared with females at 16% [OR = 4.3, 95%CI 1.4-13.1, P < 0.008]) and psychotic features (23%). Psychiatric diagnoses did not differ between mUPD15 vs deletion, but a greater number of psychiatric diagnoses were observed for the larger Type I (4.3) vs smaller Type II (3.6) deletions when age was controlled (F = 5.0, P < 0.04). Adults with PWS presented with uniformly higher rates of psychiatric comorbidities which differed by genetic subtype with gender-specific trends. PMID- 28984910 TI - Myocardial Reperfusion Injury: Fact or Myth? A 1993 Appraisal of a Seemingly Endless Controversy a. PMID- 28984909 TI - Impact of maternal vaccination timing and influenza virus circulation on birth outcomes in rural Nepal. AB - OBJECTIVE: To describe the effect of maternal vaccination on birth outcomes in rural Nepal, modified by timing of vaccination in pregnancy and influenza virus activity. METHODS: A secondary analysis was conducted using data from two annual cohorts of a randomized controlled trial. A total of 3693 pregnant women from Sarlahi District were enrolled between April 25, 2011, and September 9, 2013. All participants were aged 15-40 years and received a trivalent inactivated influenza vaccine or placebo. The outcome measures included birth weight, pregnancy length, low birth weight (<2500 g), preterm birth, and small-for-gestational-age birth. RESULTS: Data were available on birth weight for 2741 births and on pregnancy length for 3623 births. Maternal vaccination increased mean birthweight by 42 g (95% confidence interval [CI] 8-76). The magnitude of this increase varied by season but was greatest among pregnancies with high influenza virus circulation during the third trimester. Birth weight increased by 111 g (95% CI -51 to 273) when 75%-100% of a pregnancy's third trimester had high influenza virus circulation versus 38 g (95% CI -6 to 81) when 0%-25% of a pregnancy's third trimester had high influenza virus circulation. However, these results were nonsignificant. CONCLUSION: Seasonal maternal influenza vaccination in rural Nepal increased birth weight; the magnitude appeared larger during periods of high influenza virus circulation. CLINICALTRIALS.GOV: NCT01034254. PMID- 28984911 TI - A molecular approach to drought-induced reduction in leaf CO2 exchange in drought resistant Quercus ilex. AB - Drought-induced reduction of leaf gas exchange entails a complex regulation of the plant leaf metabolism. We used a combined molecular and physiological approach to understand leaf photosynthetic and respiratory responses of 2-year old Quercus ilex seedlings to drought. Mild drought stress resulted in glucose accumulation while net photosynthetic CO2 uptake (Pn ) remained unchanged, suggesting a role of glucose in stress signaling and/or osmoregulation. Simple sugars and sugar alcohols increased throughout moderate-to-very severe drought stress conditions, in parallel to a progressive decline in Pn and the quantum efficiency of photosystem II; by contrast, minor changes occurred in respiration rates until drought stress was very severe. At very severe drought stress, 2 oxoglutarate dehydrogenase complex gene expression significantly decreased, and the abundance of most amino acids dramatically increased, especially that of proline and gamma-aminobutyric acid (GABA) suggesting enhanced protection against oxidative damage and a reorganization of the tricarboxylic cycle acid cycle via the GABA shunt. Altogether, our results point to Q. ilex drought tolerance being linked to signaling and osmoregulation by hexoses during early stages of drought stress, and enhanced protection against oxidative damage by polyols and amino acids under severe drought stress. PMID- 28984912 TI - Variability of pesticide residues in eggplant units collected from a field trial and marketplaces in Greece. AB - BACKGROUND: Variability of pesticide residues among food items is very important when assessing the risks and food safety for the consumers. Therefore, the present study was undertaken to estimate the unit-to-unit residue variability factors for eggplant. RESULTS: In total, 120 samples from a trial field and 142 samples from different marketplaces in Thessaloniki, Greece, were collected to estimate the variability of pesticide residues in eggplant units. They were extracted by the QuEChERS method and the residues were determined by LC-MS/MS. For the field samples, the unit-to-unit variability factors (VFs) obtained for cypermethrin and deltamethrin residues were 2.54 and 2.51, respectively. The mean residue levels of both pesticides were higher in the composite samples than in the individual samples. The average VFs for the marketplace samples was 3.89. The eggplant units exposed to pesticides were higher in residues than the non-exposed units. CONCLUSION: The variability factors obtained in the marketplace samples were higher than those in the samples collected from the field trial. A default VF value of 3 for field trials is appropriate for use when assessing the acute dietary intake but a VF for the marketplace samples should be reconsidered with a larger data. (c) 2017 Society of Chemical Industry. PMID- 28984914 TI - Morphological Manifestations of Reperfusion Injury in Brain a. PMID- 28984913 TI - Ischemia-Reperfusion Injury to the Lung a. PMID- 28984915 TI - Ischemia And Reperfusion Induced Alterations In Membrane Phospholipids: An Overview a. PMID- 28984916 TI - Preconditioning and Antioxidant Defense against Reperfusion Injury a. PMID- 28984917 TI - Ischemic Preconditioning against Arrhythmias: An Anti-Arrhythmic or an Anti Ischemic Phenomenon? PMID- 28984918 TI - The pH Paradox in the Pathophysiology of Reperfusion Injury to Rat Neonatal Cardiac Myocytes a. PMID- 28984919 TI - Evidence Implicating Xanthine Oxidase and Neutrophils in Reperfusion-Induced Microvascular Dysfunction a. PMID- 28984920 TI - Heat-Shock Proteins, Stress, and the Heart. PMID- 28984921 TI - Cytokines, Neuropeptides, and Reperfusion Injury during Magnesium Deficiency a. PMID- 28984922 TI - Lipid Peroxidation-Derived Free Radical Production and Postischemic Myocardial Reperfusion Injurya. PMID- 28984923 TI - B cell tolerance to epidermal ribonuclear-associated neo-autoantigen in vivo. AB - Defining how self-antigens are perceived by the immune system is pivotal to understand how tolerance is maintained under homeostatic conditions. Clinically relevant, natural autoantigens targeted by autoantibodies, in e.g. systemic lupus erythematosus (SLE), commonly have an intrinsic ability to engage not only the B cell receptor (BCR), but also a co-stimulatory pathway in B cells, such as the Toll-like receptor (TLR)-7 pathway. Here we developed a novel mouse model displaying inducible expression of a fluorescent epidermal neo-autoantigen carrying an OT-II T cell epitope, B cell antigen and associated ribonucleic acids capable of stimulating TLR-7. The neo-autoantigen was expressed in skin, but did not drain in intact form into draining lymph nodes, even after ultraviolet B (UVB)-stimulated induction of apoptosis in the basal layer. Adoptively transferred autoreactive B cells were excluded follicularly and perished at the T B border in the spleen, preventing their recirculation and encounter with antigen peripherally. This transitional check-point was bypassed by crossing the reporter to a BCR knock-in line on a C4-deficient background. Adoptively transferred OT-II T cells homed rapidly into cutaneous lymph nodes and up-regulated CD69. Surprisingly, however, tolerance was not broken, as the T cells subsequently down regulated activation markers and contracted. Our results highlight how sequestration of intracellular and peripheral antigen, the transitional B cell tolerance check-point and T cell regulation co-operate to maintain immunological tolerance in vivo. PMID- 28984924 TI - Reperfusion Injury in Gastric Mucosa. PMID- 28984925 TI - Corrigendum: Individual variation in fathers' testosterone reactivity to infant distress predicts parenting behaviors with their 1-year-old infants. P. X. Kuo, E. K. Saini, E. Thomason, O. C. Schultheiss, R. Gonzalez, and B. L. Volling. PMID- 28984927 TI - Cytokines and Extrahepatic Sequelae of Ischemia-Reperfusion Injury to the Liver a. PMID- 28984926 TI - Application and optimisation of air-steam cooking on selected vegetables: impact on physical and antioxidant properties. AB - BACKGROUND: Several studies investigated the impact of different cooking techniques on the quality of vegetables. However, the use of the combined air steam cooking is still scarcely debated, despite the advantages informally referred by professional catering workers. In this study, its optimisation was studied on Brussels sprouts and pumpkin cubes to obtain the best physical (texture, colour) and antioxidant (FRAP, total phenols) response, in comparison to a conventional steaming treatment. RESULTS: Increasing the strength of the air steam treatment, Brussels sprouts resulted to be softer, less green (higher a* value), richer in phenols and exhibited lower FRAP values than the steamed ones. The air-steamed pumpkin cubes exhibited an equivalent softening degree to that of steamed ones and, under the strongest cooking conditions, a higher antioxidant quality and a yellow darkening (lower b* value). Varying the cooking time and/or temperature, a linear change of force/compression hardness and a* (negative a*: greenness) for Brussels sprouts, b* (yellowness) and total phenol content for pumpkin cubes was observed. A predictive model for these variables was obtained by response surface methodology. The best process conditions to achieve the optimal desirability were also identified. CONCLUSION: The application of air steam cooking under suitable time/temperature conditions could be proposed as an alternative method to a traditional steam cooking on Brussels sprouts and pumpkin cubes, being able to preserve or improve their quality. The best air-steam cooking conditions were 25 min at 90 degrees C for Brussels sprouts and 10 min at 110 degrees C for pumpkin. (c) 2017 Society of Chemical Industry. PMID- 28984928 TI - Clearance Time of Different Superoxide Dismutase-Albumin Complexes in Plasma and Interstitial Fluid a. PMID- 28984929 TI - Is Myocardial Infarct Size Limitation by Ischemic Preconditioning an "All or Nothing" Phenomenon?a. PMID- 28984930 TI - Oleate plus Oxfenicine Improves Functional Recovery, Assessed via an Intraventricular Balloon, in Ischemic-Reperfused Rat Hearts. PMID- 28984932 TI - Exacerbation of Both Ischemic and Reperfusion Damage by Fatty Acid in Working Rat Hearts. PMID- 28984931 TI - Patterns of Myocardial Gene Expression after Cycles of Brief Coronary Occlusion and Reperfusion. PMID- 28984933 TI - Gangliosides in Postischemic Cellular Dysfunctions. PMID- 28984934 TI - LPS-Stimulated Nitric Oxide Production Decreases Spontaneous Organ Chemiluminescence and Increases Injury during Reperfusion of Perfused Rat Liver a. PMID- 28984935 TI - Allopurinol Improves Postischemic Muscle Function but Not High-Energy Phosphate Levels. PMID- 28984936 TI - Morphology of Peroxisomes after Ischemia-Reperfusion Injury a. PMID- 28984937 TI - Decrease in Norepinephrine Release from Cardiac Adrenergic Nerve Terminals after Ischemia and Reperfusion a. PMID- 28984938 TI - CuZn Superoxide Dismutase: Intraorganellar Distribution in Peroxisomes a. PMID- 28984939 TI - K+-Channel Openers Protect the Myocardium against Ischemia-Reperfusion Injury. PMID- 28984940 TI - Disruption of Intracellular Ca2+Homeostasis in Hearts Reperfused after Prolonged Episodes of Ischemia a. PMID- 28984941 TI - Effects of Dimethylthiourea on the Cardiac Function and Oxyradical Status in Ischemia-Reperfusion Injury a. PMID- 28984942 TI - Morphometry of Reversible Myocardial Damage. PMID- 28984943 TI - Role of Free Radicals in Hepatic Reperfusion Injury. PMID- 28984944 TI - On the Reversal of Myocardial Stunning: A Role for Ca2+-Sensitizers. PMID- 28984945 TI - Time Course of Free Radicals Formation, Lipid Peroxidation, and Reoxygenation Injury in Perfused Rat Hepatocytes. PMID- 28984946 TI - Myocardial Salvage by Chimyl Alcohol: Possible Role of Peroxisomal Dysfunction in Reperfusion Injury. PMID- 28984947 TI - Regional Expression of Immediate-Early Genes and Heat-Shock Genes after Cerebral Ischemia a. PMID- 28984948 TI - The Effects of Platelet Activating Factor Antagonist, TCV309, on the Relationship between Electrophysiological and Mechanical Status during Myocardial Ischemia and Reperfusion. PMID- 28984949 TI - Role of Phospholipase A2, C, and D Activities during Myocardial Ischemia and Reperfusion a. PMID- 28984950 TI - Extracellular Magnesium Manipulation Reduces Reperfusion Arrhythmias and Ion Shifts in Isolated Rat Hearts. PMID- 28984951 TI - Ceruloplasmin and Deferoxamine Prevent Ischemia-Reperfusion Damage in Kidney Transplantation. PMID- 28984952 TI - ESR Evidence of Attenuation of Hydroxyl Radical Generation in Rat Cerebral Ischemia-Reperfusion Model by Oxypurinol. PMID- 28984953 TI - Endothelin-Induced Response of the Phosphatidylinositol Cycle in Cultured Cardiomyocytes Exposed to Substrate-Free Hypoxia-Reoxygenation a. PMID- 28984954 TI - Depression of Myocardial Contractility Is Not a Causative Factor for Circulatory Deterioration in Two Experimental Models of Shock in Anesthetized Dogs. PMID- 28984955 TI - Ischemia Potentiates the Mechanosensitive Modulation of Atrial ATP-Sensitive Potassium Channels a. PMID- 28984956 TI - Salutary Effects of Dopexamine, a DA-1 and beta-2 Agonist, on Free Radical Induced Toxicity in Anesthetized Rats. PMID- 28984957 TI - The Contribution of Hypoxia-Reperfusion Injury to Inflammatory Synovitis: The Influence of Reactive Oxygen Intermediates on the Transcriptional Control of Inflammation. PMID- 28984958 TI - Neutrophils and the Endothelium in Post-Ischemic Alterations in Skeletal Muscle Blood Flow. PMID- 28984959 TI - Functional Assessment of the Efficacy of Oxygen Free Radical Scavengers in the "No-Reflow" Phenomenon in Skeletal Muscle. PMID- 28984960 TI - Gene Expression during Myocardial Adaptation to Ischemia and Reperfusion a. PMID- 28984961 TI - The Effect of Immunosuppressants on Human Leukocyte NADPH Oxidase a. PMID- 28984962 TI - Prevention of Reperfusion Injury in Skeletal Muscle. PMID- 28984963 TI - Protein Kinase C and Gene Expression in Prolactin-Stimulated Postischemic Livers a. PMID- 28984964 TI - Neutrophils and Skeletal Muscle Reperfusion Injury. PMID- 28984965 TI - Introduction. PMID- 28984966 TI - Formation of 4-Hydroxyalkenals by the Reperfusion-Injured Rat Heart a. PMID- 28984967 TI - Creatine Kinase-BB and Soluble Thrombomodulin: New Markers for Sinusoidal Damage in Human Liver Transplantation. PMID- 28984968 TI - The ATP-Regulated Potassium Channel in Ischemia-Reperfusion Injury. PMID- 28984969 TI - Bidirectional, Transmembranal Protein Shifts in Hippocampal Neurons during Early Postischemic Reperfusion of the Gerbil Brain. PMID- 28984970 TI - Leukotriene Generation and Pulmonary Dysfunction following Aortic Cross Clamp in Humans. PMID- 28984971 TI - Role of Leukocytes during the Early Phase of Reperfusion Injury after Cold Preservation of Rat Liver. PMID- 28984973 TI - Changed Relation between Phosphorylation Potential and Left Ventricular Developed Pressure in Guinea Pig Hearts during Ischemia-Reperfusion a. PMID- 28984972 TI - Selenium, Free Radicals, and Intestinal Ischemia-Reperfusion Injury: An Experimental Study in the Rat. PMID- 28984974 TI - Role of Calcium Channel Blockers in Postischemic Lungs. PMID- 28984975 TI - Role of Endothelin in Ischemia-Reperfusion Injury. PMID- 28984976 TI - Extreme Hypoxia Decreases the Adherence of Granulocytes to Endothelial Cells in Vitroa. PMID- 28984977 TI - A New Extracorporeal Perfusion System: Prolongation of Liver Organ Vitality beyond 24 Hours. PMID- 28984978 TI - The Effects of Reduced Perfusion and Reperfusion on C-Fos Protei Immunohistochemistry in Gestational Day 21 Rat Brains a. PMID- 28984979 TI - Molecular Response to Calcium Channel Blockers Expressed during Reperfusion following Acute Renal Ischemia. PMID- 28984980 TI - The Scavenging of Oxygen Free Radicals by Angiotensin Converting Enzyme Inhibitors: The Importance of the Sulfhydryl Group in the Chemical Structure of the Compounds. PMID- 28984981 TI - VIP Enhances and Nitric Oxide Synthase Inhibitor Reduces Survival of Rat Lungs Perfused ex Vivo. PMID- 28984982 TI - Protective Effects of Prostaglandin I2 Analogues on Superoxide-Induced Hepatocyte Injury. PMID- 28984983 TI - The Role of Systemic Prostaglandins during Human Liver Transplantation a. PMID- 28984984 TI - Nitric Oxide: A Potent Mediator of Glutamatergic Neurotoxicity in Brain Ischemia. PMID- 28984985 TI - Cellular Mechanisms in Ischemic Preconditioning: The Role of Adenosine and Protein Kinase C a. PMID- 28984986 TI - Ischemic Preconditioning Slows Ischemic Metabolism and Limits Myocardial Infarct Size a. PMID- 28984987 TI - Expression and Immunohistochemical Localization of Heat-Shock Protein-70 in Preconditioned Porcine Myocardium. PMID- 28984988 TI - Role of Calcium in Reperfusion Injury of the Kidney. PMID- 28984990 TI - Nitric Oxide Mediates Oxidant Tissue Injury Caused by Paraquat and Xanthine Oxidase. PMID- 28984989 TI - Treating murine Kala-azar with a Mayan plant induces immunochemical changes. AB - Pentalinon andrieuxii Muell Arg is a Mexican-Central American plant anciently used by local people to treat cutaneous leishmaniasis. We evaluated a hexane extract of the root we called PAE for its chemical content and for its immunochemical and in vitro activity against Leishmania donovani and healing of experimental Kala-azar. Chemical analysis using gas chromatography coupled to mass spectrometry (GC-MS) identified hexadecanoic acid, hexadecanoic acid ethyl ester, 9, 12-octadecadienoic acid ethyl ester, octadecanoic acid ethyl ester, 9 octadecenoic acid ethyl ester and diethyl phthalate as the main compounds present in PAE. We also demonstrated PAE kills promastigotes and amastigotes in vitro and significantly reduces parasite loads in liver and spleen of infected Balb/c mice. PAE induces expression of NFkB/AP-1 transcription factors and production of IL-2 and IFN-gamma by spleen cells of PAE treated but not in the untreated control mice. Furthermore, there were not IL-6, IL-10 nor TNF production in macrophages treated in vitro with PAE. We developed an affordable extract of P. andrieuxii effective to treat experimental Kala-azar in Balb/c mice. PMID- 28984991 TI - The Function of the Golgi Ribbon Structure - An Enduring Mystery Unfolds! AB - The Golgi apparatus in vertebrate cells consists of individual Golgi stacks fused together in a continuous ribbon structure. The ribbon structure per se is not required to mediate the classical functions of this organelle and the relevance of the "ribbon" structure has been a mystery since first identified ultrastructurally in the 1950s. Recent advances recognize a role for the Golgi apparatus in a range of cellular processes, some mediated by signaling networks which are regulated at the Golgi. Here we review the cellular processes and signaling events regulated by the Golgi apparatus and, in particular, explore an emerging theme that the ribbon structure of the Golgi contributes directly to the regulation of these higher order functions. PMID- 28984992 TI - Social interactions and activity patterns of old Barbary macaques: Further insights into the foundations of social selectivity. AB - Human aging is accompanied by a decrease in social activity and a narrowing in social networks. Studies in nonhuman primates may provide valuable comparative insights in which way aging impacts social life, in the absence of cultural conventions and an awareness of a limited lifetime. For female Barbary macaques at "La Foret des Singes" in Rocamadour, France, we previously reported an age associated decrease in active grooming time and network size. Here, we aimed to extend these findings by investigating in which way physical decline, spatial proximity, and aggression vary with age in female Barbary macaques. We analyzed >1,200 hr of focal observations for 46 females aged 5-29 years. As expected, older females engaged less frequently in challenging locomotor activity, such as climbing or running, than younger ones. The previously reported decrease in grooming time was not due to shorter grooming bout duration. Instead, active grooming bouts lasted even longer, which discounts the idea that manual fatigue explains the shift in grooming pattern. We found that older females tended to be spatially reclusive and that they were less frequently the targets of aggression. Although older females showed aggressive behaviors at similar rates as younger females, the proportion of low-level aggression (i.e., threats) increased with age. We suggest that these threats are not simply a signal of dominance, but also function to deter approaches by others. Overall, these findings are in line with the idea that older females aim to avoid potentially negative interactions, specifically if these are costly. In sum, these findings support the idea that shifts in female Barbary macaques' grooming activity, do not simply result from physical deterioration, but are instead due to a higher selectivity in the choice of social partners. PMID- 28984993 TI - Total synthesis of [13 C]2 -, [13 C]3 -, and [13 C]5 -isotopomers of xanthohumol, the principal prenylflavonoid from hops. AB - Xanthohumol [(E)-6'-methoxy-3'-(3-methylbuten-2-yl)-2',4',4"-trihydroxychalcone], he principal prenylated flavonoid from hops, has a complex bioactivity profile, and 13 C-labeled isotopomers of this compound are of potential use as molecular probes and as analytical standards to study metabolism and mode of action. 1,3 [13 C]2 -Xanthohumol was prepared by an adaptation of the total synthesis of Khupse and Erhardt in 7 steps and 5.7% overall yield from phloroglucinol by a route incorporating a cascade Claisen-Cope rearrangement to install the 3'-prenyl moiety from a 5'-prenyl aryl ether and an aldol condensation between 1-[13 C] 2',4'-bis(benzyloxymethyloxy)-6'-methoxy-3'-(3-methylbuten-2-yl)acetophenone and 1'-[13 C]-4-(methoxymethyloxy)benzaldehyde. The 13 C-atom in the methyl ketone was derived from 1-[13 C]-acetyl chloride while that in the aryl aldehyde was derived from [13 C]-iodomethane. Tri- and penta-13 C-labeled xanthohumols were similarly prepared by applying minor modifications to the route. PMID- 28984994 TI - Novel bi-allelic splice mutations in CARD9 causing adult-onset Candida endophthalmitis. AB - CARD9 deficiency (CANDF2; OMIM# 212050) is an autosomal-recessive monogenic inborn error of immunity conferring susceptibility to invasive fungal diseases, including the very distinct syndrome of spontaneous central nervous system candidiasis, in which opportunistic yeast of the genus Candida infect the central nervous system (either brain parenchyma and/or meninges) in the absence of trauma, chemotherapy or underlying systemic disease. We present a patient with spontaneous endophthalmitis of the right eye due to Candida albicans; further investigations revealed concomitant cerebral abscess. She had a history of left endophthalmitis due to the dematiaceous mould, Aureobasidium pullulans, 15 years earlier. Targeted sequencing of the CARD9 gene revealed 2 novel variants (c.184G>A and c.288C>T). Analysis in silico predicted each variant altered splicing, which was confirmed by sequencing of cDNA from proband and carrier offsprings: c.184G>A results in a 4-base pair frameshift deletion with loss of allelic expression; c.288C>T results in an in-frame 36-bp pair deletion with detectable protein. CARD9 deficiency can present with a phenotype of spontaneous candidal endophthalmitis. We report 2 novel mutations in CARD9, both affecting splicing, expanding the range of morbid variants causing CARD9 deficiency, emphasising the importance of both genomic and cDNA sequencing for this condition. PMID- 28984995 TI - Giant Room-Temperature Magnetodielectric Response in a MOF at 0.1 Tesla. AB - A giant room-temperature magnetodielectric (MD) response upon the application of a small magnetic field is of fundamental importance for the practical application of a new generation of devices. Here, the giant room-temperature magnetodielectric response is demonstrated in the metal-organic framework (MOF) of [NH2 (CH3 )2 ]n [FeIII FeII(1-x) NiIIx (HCOO)6 ]n (x ~ 0.63-0.69) (1) with its MD coefficient remaining between -20% and -24% in the 300-410 K temperature range, even at 0.1 T. Because a room-temperature magnetodielectric response has never been observed in MOFs, the present work not only provides a new type of magnetodielectric material but also takes a solid step toward the practical application of MOFs in a new generation of devices. PMID- 28984996 TI - Electrochemical Tantalum Oxide for Resistive Switching Memories. AB - Redox-based resistive switching memories (ReRAMs) are strongest candidates for the next-generation nonvolatile memories fulfilling the criteria for fast, energy efficient, and scalable green IT. These types of devices can also be used for selector elements, alternative logic circuits and computing, and memristive and neuromorphic operations. ReRAMs are composed of metal/solid electrolyte/metal junctions in which the solid electrolyte is typically a metal oxide or multilayer oxides structures. Here, this study offers an effective and cheap electrochemical approach to fabricate Ta/Ta2 O5 -based devices by anodizing. This method allows to grow high-quality and dense oxide thin films onto a metallic substrates with precise control over morphology and thickness. Electrochemical-oxide-based devices demonstrate superior properties, i.e., endurance of at least 106 pulse cycles and/or 103 I-V sweeps maintaining a good memory window with a low dispersion in ROFF and RON values, nanosecond fast switching, and data retention of at least 104 s. Multilevel programing capability is presented with both I-V sweeps and pulse measurements. Thus, it is shown that anodizing has a great prospective as a method for preparation of dense oxide films for resistive switching memories. PMID- 28984997 TI - NLRP3/IL-1beta mediates denervation during bladder outlet obstruction in rats. AB - AIMS: Denervation of the bladder is a detrimental consequence of bladder outlet obstruction (BOO). We have previously shown that, during BOO, inflammation triggered by the NLRP3 inflammasome in the urothelia mediates physiological bladder dysfunction and downstream fibrosis in rats. The aim of this study was to assess the effect of NLRP3-mediated inflammation on bladder denervation during BOO. METHODS: There were five groups of rats: (i) Control (no surgery); (ii) Sham operated; (iii) BOO rats given vehicle; (iv) BOO rats given the NLRP3 inhibitor glyburide; and (v) BOO rats given the IL-1 receptor antagonist anakinra. BOO was constructed by ligating the urethra over a 1 mm catheter and removing the catheter. Medications were given prior to surgery and once daily for 12 days. Bladder sections were stained for PGP9.5, a pan-neuronal marker. Whole transverse sections were used to identify and count nerves while assessing cross-sectional area. For in vitro studies, pelvic ganglion neurons were isolated and treated with IL-1beta. After a 48 h incubation apoptosis, neurite length and branching were assessed. RESULTS: In obstructed bladders, the number of nerves decreased while total area increased, indicating a loss of cell number and/or branching. The decrease in nerve density was blocked by glyburide or anakinra, clearly implicating the NLRP3 pathway in denervation. In vitro analysis demonstrated that IL-1beta, a product of the inflammasome, induced apoptosis in pelvic ganglion neurons, suggesting one mechanism of BOO-induced denervation is NLRP3/IL-1beta triggered apoptosis. CONCLUSIONS: The NLRP3/IL-1beta-mediated inflammation pathway plays a significant role in denervation during BOO. PMID- 28984998 TI - Biofluorescence as a survey tool for cryptic marine species. AB - As ecosystems come under increasing anthropogenic pressure, rare species face the highest risk of extinction. Paradoxically, data necessary to evaluate the conservation status of rare species are often lacking because of the challenges of detecting species with low abundance. One group of fishes subject to this undersampling bias are those with cryptic body patterns. Twenty-one percent of cryptic fish species assessed for their extinction risk (International Union for Conservation of Nature [IUCN]) are data deficient. We developed a nondestructive method for surveying cryptically patterned marine fishes based on the presence of biofluorescence (underwater biofluorescence census, UBC). Blue LED torches were used to investigate how widespread biofluorescence was in cryptic reef fishes in the Coral Triangle region. The effectiveness of UBC to generate abundance data was tested on a data-deficient pygmy seahorse species (Hippocampus bargibanti) and compared with data obtained from standard underwater visual census (UVC) surveys. We recorded 95 reef fish species displaying biofluorescence, 73 of which had not been previously described as biofluorescent. Of those fish with cryptic patterns, 87% were biofluorescent compared with 9% for noncryptic fishes. The probability of species displaying biofluorescence was 70.9 times greater for cryptic species than for noncryptic species. Almost twice the number of H. bargibanti was counted using the UBC compared with UVC. For 2 triplefin species (Ucla xenogrammus, Enneapterygius tutuilae), the abundance detected with UBC was triple that detected with UVC. The UBC method was effective at finding cryptic species that would otherwise be difficult to detect and thus will reduce interobserver variability inherent to UVC surveys. Biofluorescence is ubiquitous in cryptic fishes, making this method applicable across a wide range of species. Data collected using UBC could be used with multiple IUCN criteria to assess the extinction risk of cryptic species. Adopting this technique will enhance researchers' ability to survey cryptic species and facilitate management and conservation of cryptic marine species. PMID- 28984999 TI - Direct immunofluorescence testing in vasculitis-A single institution experience with Henoch-Schonlein purpura. AB - BACKGROUND: Direct immunofluorescence (DIF) panels (IgG, IgA, IgM, C3 and fibrinogen) are ordered for clinically suspected vasculitis, with frequently negative results. METHODS: Cases submitted for DIF and histology (2010-2014) with "vasculitis" in the clinical data were examined, and the electronic medical record reviewed for clinical suspicion of Henoch-Schonlein purpura (HSP). Peri/intravascular IgA was considered positive, other reactants non-specific and no immunoreactivity negative. RESULTS: Vasculitis was the given indication for 20% (258/1318) of DIF studies. HSP was clinically suspected in 36% (95/258). In this setting, leukocytoclastic vasculitis (LCV) was common (66%, 63/95) and DIF was positive in 43% (27/63). One hundred percentage of DIF+ had LCV+. In cases without HSP suspicion, 26% (42/163) were LCV+ and <1% DIF+. Of the 258 cases, LCV+ greatly enriched for DIF+ (105/258 LCV+ with 28/105 [27%] DIF+), captured 100% of HSP and included cases with non-specific DIF/etiologic findings. In LCV cases, DIF positivity was not seen, HSP was not diagnosed and non-specific DIF findings were common. CONCLUSIONS: LCV is an H&E-based histopathologic diagnosis that can have positive, negative and non-specific DIF results that are rarely contributory except in the setting of HSP, where DIF is best utilized with IgA as the sole immunoreactant. H&E-based triage of DIF orders is recommended. PMID- 28985000 TI - Autonomous Ex Novo Chemical Assembly with Blebbing and Division of Functional Polymer Vesicles from a "Homogeneous Mixture". AB - The chemical energy and radicals from an oscillating chemical reaction are used to synthesize a polymer vesicle from a homogeneous solution of monomeric units. Periodically formed radicals from the Belousov-Zhabotinsky (B-Z) reaction initiate radical polymerization between a polyethylene glycol based chain transfer agent (PEG-CTA) and hydrophilic acrylonitrile monomers in water. The growth of a hydrophobic chain on the hydrophilic PEG chain induces self-assembly of polymeric amphiphiles to form micrometer-sized vesicles entrapping an active oscillating B-Z reaction. In our experimental conditions, the different chemical environments inside and outside the vesicles contribute to enlarge the area and diameter of the resulting self-assembled vesicles and, in some cases, promote blebbing and division. PMID- 28985001 TI - GBF1 and Arf1 function in vesicular trafficking, lipid homoeostasis and organelle dynamics. AB - The ADP-ribosylation factor (Arf) small G proteins act as molecular switches to coordinate multiple downstream pathways that regulate membrane dynamics. Their activation is spatially and temporally controlled by the guanine nucleotide exchange factors (GEFs). Members of the evolutionarily conserved GBF/Gea family of Arf GEFs are well known for their roles in formation of coat protein complex I (COPI) vesicles, essential for maintaining the structure and function of the Golgi apparatus. However, studies over the past 10 years have found new functions for these GEFs, along with their substrate Arf1, in lipid droplet metabolism, clathrin-independent endocytosis, signalling at the plasma membrane, mitochondrial dynamics and transport along microtubules. Here, we describe these different functions, focussing in particular on the emerging theme of GFB1 and Arf1 regulation of organelle movement on microtubules. PMID- 28985002 TI - A Twisted Thieno[3,4-b]thiophene-Based Electron Acceptor Featuring a 14-pi Electron Indenoindene Core for High-Performance Organic Photovoltaics. AB - With an indenoindene core, a new thieno[3,4-b]thiophene-based small-molecule electron acceptor, 2,2'-((2Z,2'Z)-((6,6'-(5,5,10,10-tetrakis(2-ethylhexyl)-5,10 dihydroindeno[2,1-a]indene-2,7-diyl)bis(2-octylthieno[3,4-b]thiophene-6,4 diyl))bis(methanylylidene))bis(5,6-difluoro-3-oxo-2,3-dihydro-1H-indene-2,1 diylidene))dimalononitrile (NITI), is successfully designed and synthesized. Compared with 12-pi-electron fluorene, a carbon-bridged biphenylene with an axial symmetry, indenoindene, a carbon-bridged E-stilbene with a centrosymmetry, shows elongated pi-conjugation with 14 pi-electrons and one more sp3 carbon bridge, which may increase the tunability of electronic structure and film morphology. Despite its twisted molecular framework, NITI shows a low optical bandgap of 1.49 eV in thin film and a high molar extinction coefficient of 1.90 * 105 m-1 cm-1 in solution. By matching NITI with a large-bandgap polymer donor, an extraordinary power conversion efficiency of 12.74% is achieved, which is among the best performance so far reported for fullerene-free organic photovoltaics and is inspiring for the design of new electron acceptors. PMID- 28985003 TI - The APSES protein Sok2 is a positive regulator of sporulation in Ashbya gossypii. AB - Ashbya gossypii is a homothallic, flavinogenic, filamentous ascomycete that starts overproduction of riboflavin and fragments its mycelium quantitatively into spore producing sporangia at the end of a growth phase. Mating is not required for sporulation and the standard homothallic laboratory strain is a MATa strain. Here we show that ectopic expression of Saccharomyces cerevisiae MATalpha2 in A. gossypii completely suppresses sporulation, inhibits riboflavin overproduction and downregulates among others AgSOK2. AgSok2 belongs to a fungal specific group of (APSES) transcription factors. Deletion of AgSOK2 strongly reduces riboflavin production and blocks sporulation. The initiator of meiosis, AgIME1, is a transcription factor essential for sporulation. We characterized the AgIME1 promoter region required for complementation of the Agime1 mutant. Reporter assays with AgIME1 promoter fragments fused to lacZ showed that AgSok2 does not control AgIME1 transcription. However, global transcriptome analysis identified two other essential regulators of sporulation, AgIME2 and AgNDT80, as potential targets of AgSok2. Our data suggest that sporulation and riboflavin production in A. gossypii are under mating type locus and nutritional control. Sok2, a target of the cAMP/protein kinase A pathway, serves as a central positive regulator to promote sporulation. This contrasts Saccharomyces cerevisiae where Sok2 is a repressor of IME1 transcription. PMID- 28985005 TI - On-Demand Reconfiguration of Nanomaterials: When Electronics Meets Ionics. AB - Rapid advances in the semiconductor industry, driven largely by device scaling, are now approaching fundamental physical limits and face severe power, performance, and cost constraints. Multifunctional materials and devices may lead to a paradigm shift toward new, intelligent, and efficient computing systems, and are being extensively studied. Herein examines how, by controlling the internal ion distribution in a solid-state film, a material's chemical composition and physical properties can be reversibly reconfigured using an applied electric field, at room temperature and after device fabrication. Reconfigurability is observed in a wide range of materials, including commonly used dielectric films, and has led to the development of new device concepts such as resistive random access memory. Physical reconfigurability further allows memory and logic operations to be merged in the same device for efficient in-memory computing and neuromorphic computing systems. By directly changing the chemical composition of the material, coupled electrical, optical, and magnetic effects can also be obtained. A survey of recent fundamental material and device studies that reveal the dynamic ionic processes is included, along with discussions on systematic modeling efforts, device and material challenges, and future research directions. PMID- 28985004 TI - Efficient ASK-assisted system for expression and purification of plant F-box proteins. AB - Ubiquitin-mediated protein degradation plays an essential role in plant growth and development as well as responses to environmental and endogenous signals. F box protein is one of the key components of the SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex, which recruit specific substrate proteins for subsequent ubiquitination and 26S proteasome-mediated degradation to regulate developmental processes and signaling networks. However, it is not easy to obtain purified F-box proteins with high activity due to their unstable protein structures. Here, we found that Arabidopsis SKP-like proteins (ASKs) can significantly improve soluble expression of F-box proteins and maintain their bioactivity. We established an efficient ASK-assisted method to express and purify plant F-box proteins. The method meets a broad range of criteria required for the biochemical analysis or protein crystallization of plant F-box proteins. PMID- 28985006 TI - Thermoreversible Self-Assembly of Perfluorinated Core-Coronas Cellulose Nanoparticles in Dry State. AB - Self-assembly of nanoparticles (NPs) forming unique structures has been investigated extensively over the past few years. However, many self-assembled structures by NPs are irreversible, because they are generally constructed using their suspensions. It is still challenging for NPs to reversibly self-assemble in dry state, let alone of polymeric NPs with general sizes of hundreds of nm. Herein, this study reports a new reversible self-assembly phenomenon of NPs in dry state, forming thermoreversible strip-like supermolecular structures. These novel NPs of around 150 nm are perfluorinated surface-undecenoated cellulose nanoparticles (FSU-CNPs) with a core-coronas structure. The thermoreversible self assembled structure is formed after drying in the air at the interface between FSU-CNP films and Teflon substrates. Remarkably, the formation and dissociation of this assembled structure are accompanied by a reversible conversion of the surface hydrophobicity, film transparency, and anisotropic properties. These findings show novel feasibility of reversible self-assembly of NPs in dry state, and thereby expand our knowledge of self-assembly phenomenon. PMID- 28985007 TI - Lithiation Mechanism of Tunnel-Structured MnO2 Electrode Investigated by In Situ Transmission Electron Microscopy. AB - Manganese oxide (alpha-MnO2 ) has been considered a promising energy material, including as a lithium-based battery electrode candidate, due to its environmental friendliness. Thanks to its unique 1D [2 * 2] tunnel structure, alpha-MnO2 can be applied to a cathode by insertion reaction and to an anode by conversion reaction in corresponding voltage ranges, in a lithium-based battery. Numerous reports have attributed its remarkable performance to its unique tunnel structure; however, the precise electrochemical reaction mechanism remains unknown. In this study, finding of the lithiation mechanism of alpha-MnO2 nanowire by in situ transmission electron microscopy (TEM) is reported. By elaborately modifying the existing in situ TEM experimental technique, rapid lithium-ion diffusion through the tunnels is verified. Furthermore, by tracing the full lithiation procedure, the evolution of the MnO intermediate phase and the development of the MnO and Li2 O phases with preferred orientations is demonstrated, which explains how the conversion reaction occurs in alpha-MnO2 material. This study provides a comprehensive understanding of the electrochemical lithiation process and mechanism of alpha-MnO2 material, in addition to the introduction of an improved in situ TEM biasing technique. PMID- 28985008 TI - Transcellular vesicular transport in epithelial and endothelial cells: Challenges and opportunities. AB - Vesicle-mediated transcellular transport or simply "transcytosis" is a cellular process used to shuttle macromolecules such as lipoproteins, antibodies, and albumin from one surface of a polarized cell to the other. This mechanism is in contrast to the transit of small molecules such as anions, cations and amino acids that occur via uptake, diffusion through the cytosol and release and is also distinct from paracellular leak between cells. Importantly, transcytosis has evolved as a process to selectively move macromolecules between 2 neighboring yet unique microenvironments within a multicellular organism. Examples include the movement of lipoproteins out of the circulatory system and into tissues and the delivery of immunoglobulins to mucosal surfaces. Regardless of whether the transport is conducted by endothelial or epithelial cells, the process often involves receptor-mediated uptake of a ligand into an endocytic vesicle, regulated transit of the carrier through the cytoplasm and release of the cargo via an exocytic event. While transcytosis has been examined in detail in epithelial cells, for both historical and technical reasons, the process is less understood in endothelial cells. Here, we spotlight aspects of epithelial transcytosis including recent findings and review the comparative dearth of knowledge regarding the process in endothelial cells highlighting the opportunity for further study. PMID- 28985009 TI - Odontogenic myxoma: A 63-year retrospective multicenter study of 85 cases in a Brazil population and a review of 999 cases from literature. AB - BACKGROUND: Odontogenic myxoma (OM) is an uncommon neoplasm of the jaws. Considering the importance of defining the relative incidence and demographic profile of these lesions in South America, the aim of this study was to analyze the clinical and imagiological features of OM from three South American oral pathology services and to discuss these findings in light of the literature. METHODS: Data regarding age, gender, anatomic site, and imagiological features from 85 cases of OM were collected. Additionally, we did a review of OM studies published in three electronic databases. RESULTS: Among 63 450 oral biopsies, 1178 (1.85%) were odontogenic tumors (World Health Organization - 2017), of which 85 (7.21%) met the criteria of OM. The mean age was 30.7 years (range: 10-61 years; SD: 12.22). Forty-five (52.9%) cases occurred in females and 40 (47.1%) in males (ratio: 1:1.12). Maxilla was affected in 44 cases (53%) and mandible in 39 (47%). Of the 41 informed cases (48.2%), all of them were radiolucent lesions. The literature review indicated a majority of mean ages in third decade and a predilection for females, mandible, and multilocular radiolucent lesions. CONCLUSIONS: The features of OM samples have strong similarity to that reported in studies from other continents. It is possible to infer that geographic variation does not help to explain some differences observed in the clinical features of OM. PMID- 28985010 TI - Gold Nanoparticles on Polymer-Wrapped Carbon Nanotubes: An Efficient and Selective Catalyst for the Electroreduction of CO2. AB - Multiple approaches will be needed to reduce the atmospheric CO2 levels, which have been linked to the undesirable effects of global climate change. The electroreduction of CO2 driven by renewable energy is one approach to reduce CO2 emissions while producing chemical building blocks, but current electrocatalysts exhibit low activity and selectivity. Here, we report the structural and electrochemical characterization of a promising catalyst for the electroreduction of CO2 to CO: Au nanoparticles supported on polymer-wrapped multiwall carbon nanotubes. This catalyst exhibits high selectivity for CO over H2 : 80-92 % CO, as well as high activity: partial current density for CO as high as 160 mA cm-2 . The observed high activity, originating from a high electrochemically active surface area (23 m2 g-1 Au), in combination with the low loading (0.17 mg cm-2 ) of the highly dispersed Au nanoparticles underscores the promise of this catalyst for efficient electroreduction of CO2 . PMID- 28985011 TI - Dental students' and staff perceptions of the impact of learning environment disruption on their learning and teaching experiences. AB - INTRODUCTION: This project is a qualitative investigation into student and staff experiences of the effect of a major building redevelopment on their Dental School learning and teaching environments. Currently, there is little research exploring the impact of disruptions to the learning environment on students' learning and staff teaching experiences. METHOD: Data were collected in 2016 using an online survey, semi-structured interviews and focus groups with students and staff. Data were analysed using a general inductive approach. RESULTS: Four broad themes emerged as follows: (i) students valued having a space for personal and collaborative work within the Dental School; (ii) both staff and students positioned staff contributions to learning experiences above the role of the physical learning environment; (iii) the majority of staff and students not feel that the physical environment limited their clinical training; and (iv) staff and students were able to adapt to the impact of building redevelopment through resilience and organisation. DISCUSSION: Results of this research have informed the provision of collegial spaces at the School, both as the building redevelopment continues, and in planning for the completed building. PMID- 28985012 TI - Expression level of CXCL7 in peripheral blood cells is a potential biomarker for the diagnosis of renal cell carcinoma. AB - There are no blood biomarkers for the diagnosis of renal cell carcinoma (RCC) in routine clinical use. We focused on the gene expression profile of peripheral blood cells obtained from RCC patients to discover novel biomarkers for RCC diagnosis. Using microarray analysis and quantitative verification, CXCL7 was shown to be significantly upregulated in the peripheral blood cells of RCC patients. Importantly, aberrant CXCL7 expression was confirmed even in peripheral blood cells obtained from early stage (pT1a) RCC patients, and the expression level of CXCL7 in peripheral blood cells was a potential independent biomarker for the diagnosis of RCC by receiver operating characteristic curve analysis (sensitivity, 70.0%; specificity, 64.0%; area under the curve = 0.722; multiple logistic regression analysis: odds ratio, 1.07; 95% confidence interval, 1.03 1.11; P = 0.0004). Moreover, CXCL7 expression in peripheral blood cells significantly decreased after resection of the primary tumor. CXCL7 is more highly expressed in PBMCs than in neutrophils from both healthy controls and RCC patients. Interestingly, CXCL7 expression in PBMCs from healthy volunteers was significantly elevated following coculture with RCC cells compared to those cocultured with normal cells as a control. These results suggest that aberrant CXCL7 expression in peripheral blood cells is induced by RCC cells and may serve as a novel biomarker in the diagnosis of RCC. PMID- 28985013 TI - HDAC2/3 binding and deacetylation of BubR1 initiates spindle assembly checkpoint silencing. AB - BubR1 acetylation is essential in spindle assembly checkpoint (SAC) signaling. Here we show that BubR1 deacetylation is a signal that initiates mitotic exit. Sustained BubR1 acetylation arrests the cells in metaphase, although chromosome congression is achieved. BubR1 deacetylation was coordinated with dephosphorylation in mitotic exit, suggesting the presence of a coordinated acetylation-phosphorylation code in mitotic signaling. Histone deacetylase (HDAC) 2 and 3 bound to acetylated BubR1 exclusively in mitosis and led to the polyubiquitination of BubR1. Subsequent degradation of BubR1 resulted in the disassembly of the mitotic checkpoint complex. Importantly, BRCA2 was required for HDAC2/3 association with acetylated BubR1 in nocodazole (Noc)-arrested cells. Plk1, PP2A, P300/CBP-associated factor (PCAF) and BubR1 were found in the mitotic BRCA2 complex, suggesting that BRCA2 acts as a signaling scaffold for BubR1 modification. Furthermore, we show that Plk1 is required for BRCA2 to localize at the prometaphase kinetochore (KT). Inhibition of Plk1 resulted in the loss of BRCA2 from the KT, and so did PCAF, consistent with the loss of BubR1 acetylation. Concordantly, BRCA2-dysfunctional cells exhibited resistance to trichostatin A, which was restored when BRCA2 was introduced. That loss of Brca2 conferred resistance to various HDAC inhibitors was corroborated by the experiments in mouse pancreatic organoids. These results suggest that the BRCA2 BubR1 acetylation-deacetylation pathway is an important decision-making point for the HDAC inhibitor response. Taken together, BRCA2 is a signaling platform for BubR1, and BubR1 deacetylation is a cue for SAC silencing. PMID- 28985015 TI - Emerging materials for sample preparation. AB - This review provides an update on the implementation of emerging materials as sorbents for sample preparation in combination with chromatographic separation. We have focused on recent applications of metal-organic frameworks, layered double hydroxides, porous carbons obtained from polymers or biomass precursors, and silicates (clays and zeolites). The review is directed toward the strategies followed by the authors to engineer suitable supports enabling the application of materials with unconventional size and shape as high-performance sorbents to explore new boundaries in sample pretreatment in manual or automated modes. PMID- 28985014 TI - Cacao biotechnology: current status and future prospects. AB - Theobroma cacao-The Food of the Gods, provides the raw material for the multibillion dollar chocolate industry and is also the main source of income for about 6 million smallholders around the world. Additionally, cocoa beans have a number of other nonfood uses in the pharmaceutical and cosmetic industries. Specifically, the potential health benefits of cocoa have received increasing attention as it is rich in polyphenols, particularly flavonoids. At present, the demand for cocoa and cocoa-based products in Asia is growing particularly rapidly and chocolate manufacturers are increasing investment in this region. However, in many Asian countries, cocoa production is hampered due to many reasons including technological, political and socio-economic issues. This review provides an overview of the present status of global cocoa production and recent advances in biotechnological applications for cacao improvement, with special emphasis on genetics/genomics, in vitro embryogenesis and genetic transformation. In addition, in order to obtain an insight into the latest innovations in the commercial sector, a survey was conducted on granted patents relating to T. cacao biotechnology. PMID- 28985016 TI - A molecular biopsy test based on arteriolar under-hyalinosis reflects increased probability of rejection related to under-immunosuppression. AB - Calcineurin inhibitor immunosuppressive drugs induce changes such as arteriolar hyalinosis (ah) in kidney transplants, raising the possibility that molecular changes in biopsies related to histologic ah can provide information about drug exposure. We hypothesized that molecular changes associated with less-than expected hyalinosis might highlight a subpopulation of patients with under immunosuppression/nonadherence at intermediate times of biopsy posttransplant (TxBx). Using gene expression data from 562 indication biopsies, we developed a molecular classifier for predicting the expected ah lesions (Mah ) at a particular TxBx. Mah -scores increased linearly with log(TxBx), but some biopsies had lower scores than expected for TxBx. The deviation of individual Mah -scores below the predicted regression line of Mah -scores vs TxBx is defined as "low hyalinosis index." Low hyalinosis indices were frequent in biopsies between 3 months and 3 years posttransplant, particularly among biopsies lacking histologic hyalinosis (ah0), and were associated with T cell-mediated rejection and a subset of recent-onset antibody-mediated rejection without glomerular double contours. In patients with medical records available for review, low hyalinosis indices were frequently associated with physician-recorded concerns about nonadherence (suspected or proven). We conclude that the Mah classifier and hyalinosis index identify indication biopsies with rejection for which the possibility of patient nonadherence should be considered. PMID- 28985017 TI - Characterization of stress degradation products of amodiaquine dihydrochloride by liquid chromatography with high-resolution mass spectrometry and prediction of their properties by using ADMET PredictorTM. AB - The degradation behavior of amodiaquine dihydrochloride, an antimalarial drug, was investigated in solution as well as solid states. The drug was subjected to hydrolytic, photolytic, oxidative, and thermal stress conditions, according to International Conference on Harmonization guideline Q1A(R2). It showed extensive hydrolysis in acidic, alkaline, and neutral solutions both with and without light, while it proved to be stable to thermal and oxidative conditions. In total, six degradation products were formed, which were separated on a C8 column, employing a gradient reversed-phase high-performance liquid chromatography method in which acetonitrile and 10 mM ammonium formate (pH 3.0) were used in the mobile phase. To characterize the degradation products, mass fragmentation behavior of the drug was established by direct infusion of solution to quadrupole time-of flight and multiple-stage mass spectrometry systems. Liquid chromatography with high-resolution mass spectrometry studies were subsequently carried out on the stressed samples using the same gradient high-performance liquid chromatography method employed for the separation of the degradation products. Hydrogen/deuterium exchange studies were additionally conducted to determine the number of labile hydrogen atoms. The degradation pathway of the drug was delineated, justified by mechanistic explanation. Lastly, ADMET PredictorTM software was employed to predict relevant physicochemical and toxicity data for the degradation products. PMID- 28985018 TI - The role of graphene-based sorbents in modern sample preparation techniques. AB - The application of graphene-based sorbents in sample preparation techniques has increased significantly since 2011. These materials have good physicochemical properties to be used as sorbent and have shown excellent results in different sample preparation techniques. Graphene and its precursor graphene oxide have been considered to be good candidates to improve the extraction and concentration of different classes of target compounds (e.g., parabens, polycyclic aromatic hydrocarbon, pyrethroids, triazines, and so on) present in complex matrices. Its applications have been employed during the analysis of different matrices (e.g., environmental, biological and food). In this review, we highlight the most important characteristics of graphene-based material, their properties, synthesis routes, and the most important applications in both off-line and on-line sample preparation techniques. The discussion of the off-line approaches includes methods derived from conventional solid-phase extraction focusing on the miniaturized magnetic and dispersive modes. The modes of microextraction techniques called stir bar sorptive extraction, solid phase microextraction, and microextraction by packed sorbent are discussed. The on-line approaches focus on the use of graphene-based material mainly in on-line solid phase extraction, its variation called in-tube solid-phase microextraction, and on-line microdialysis systems. PMID- 28985019 TI - Polycyclic Polyprenylated Acylphloroglucinols: An Emerging Class of Non-Peptide Based MRSA- and VRE-Active Antibiotics. AB - In the past 20 years, peptide-based antibiotics, such as vancomycin, teicoplanin, and daptomycin, have often been considered as second-line antibiotics. However, in recent years, an increasing number of reports on vancomycin resistance in pathogens appeared, which forces researchers to find novel lead structures for potent new antibiotics. Herein, we report the total synthesis of a defined endo type B PPAP library and their antibiotic activity against multiresistant S. aureus and various vancomycin-resistant Enterococci. Four new compounds that combine high activities and low cytotoxicity were identified, indicating that the PPAP core might become a new non-peptide-based lead structure in antibiotic research. PMID- 28985020 TI - A Bayesian nonparametric test of significance chasing biases. AB - There is a growing concern that much of the published research literature is distorted by the pursuit of statistically significant results. In a seminal article, Ioannidis and Trikalinos (2007, Clinical Trials) proposed an omnibus (I&T) test for significance chasing (SC) biases. This test compares the observed number of studies that report statistically significant results, against their expected number based on study power, assuming a common effect size across studies. The current article extends this approach by developing a Bayesian nonparametric (BNP) meta-regression model and test of SC bias, which can diagnose bias at the individual study level. This new BNP test is based on a flexible model of the predictive distribution of study power, conditionally on study-level covariates which account for study diversity, including diversity due to heterogeneous effect sizes across studies. A test of SC bias proceeds by comparing each study's significant outcome report indicator against its estimated posterior predictive distribution of study power, conditionally on the study's covariates. The BNP model and SC bias test are illustrated through the analyses of 3 meta-analytic data sets and through a simulation study. Software code for the BNP model and test, and the data sets, are provided as Supporting Information. PMID- 28985021 TI - The effects of gene polymorphisms on glioma prognosis. AB - BACKGROUND: Malignant gliomas are the most common primary brain tumors. Various genetic factors play important roles in the development and prognosis of glioma. The present study focuses on the impact of MPHOSPH6, TNIP1 and several other genes (ACYP2, NAF1, TERC, TERT, OBFC1, ZNF208 and RTEL1) on telomere length and how this affects the prognosis of glioma. METHODS: Forty-three polymorphisms in nine genes from 605 glioma patients were selected. The association between genotype and survival outcome was analyzed using the Kaplan-Meier method, Cox regression analysis and the log-rank test. RESULTS: The 1-year overall survival (OS) rates of patients younger than 40 years of age was higher compared to those in patients older than 40 years of age. The 1-year OS rate of patients who underwent total resection was higher than that of patients whose gliomas were not completely resected. The 1-year OS rates of patients undergoing chemotherapy and of patients who did not undergo chemotherapy were 39.90% and 26.80%, respectively. Univariate analyses showed that ACYP2 rs12615793 and TERT rs2853676 loci affected progression-free survival in glioma patients; both ZNF208 rs8105767 and ACYP2 rs843720 affected the OS of patients with low-grade gliomas. Multivariate analyses suggested that MPHOSPH6 rs1056629 and rs1056654, and TERT rs2853676 loci were associated with good prognoses of patients with glioma or high-grade gliomas, whereas ZNF208 rs8105767 was associated with good prognosis of patients with low-grade glioma. CONCLUSIONS: Age, surgical resection and chemotherapy influenced the survival rates of glioma patients. TERT, MPHOSPH6, ACYP2 and ZNF208 genes were found to affect glioma prognosis. PMID- 28985023 TI - Determination of trace polychlorinated biphenyls and organochlorine pesticides in water samples through large-volume stir bar sorptive extraction method with thermal desorption gas chromatography. AB - A fast and sensitive analytical method based on stir bar sorptive extraction technology with gas chromatography and mass spectrometry was developed to simultaneously analyze 18 kinds of polychlorinated biphenyls and 20 kinds of organochlorine pesticides in aqueous samples. A long adsorption time and small sample volume, which are problems encountered in conventional methods of stir bar sorptive extraction, were effectively solved by simultaneously using multiple stir bars for enrichment with sequential cryofocusing and merged injection. Optimized results showed good linear coefficients in the range of 10-500 ng/L and the method detection limits of 0.12-2.07 ng/L for polychlorinated biphenyls and organochlorine pesticides. The recovery ratios of the spiked samples at different concentrations were between 64.7 and 111.0%, and their relative standard deviations ranged from 0.9 to 17.6%. Four types of the studied compounds were determined in Qiantang River water samples, and their contents were between 0.82 and 5.00 ng/L. PMID- 28985024 TI - Photoirradiation surface molecularly imprinted polymers for the separation of 6-O alpha-d-maltosyl-beta-cyclodextrin. AB - Photoirradiation surface molecularly imprinted polymers for the separation of 6-O alpha-d-maltosyl-beta-cyclodextrin were synthesized using functionalized silica as a matrix, 4-(phenyldiazenyl)phenol as a light-sensitive monomer, and 6-O-alpha d-maltosyl-beta-cyclodextrin as a template. Fourier transform infrared spectroscopy results indicated that 4-(phenyldiazenyl)phenol was grafted onto the surface of functionalized silica. The obtained imprinted polymers exhibited specific recognition toward 6-O-alpha-d-maltosyl-beta-cyclodextrin. Equilibrium binding experiments showed that the photoirradiation surface molecularly imprinted polymers obtained the maximum adsorption amount of 6-O-alpha-d-maltosyl beta-cyclodextrin at 20.5 mg/g. In binding kinetic experiments, the adsorption reached saturation within 2 h with binding capacity of 72.8%. The experimental results showed that the adsorption capacity and selectivity of imprinted polymers were effective for the separation of 6-O-alpha-d-maltosyl-beta-cyclodextrin, indicating that imprinted polymers could be used to isolate 6-O-alpha-d-maltosyl beta-cyclodextrin from a conversion mixture containing beta-cyclodextrin and maltose. The results showed that the imprinted polymers prepared by this method were very promising for the selective separation of 6-O-alpha-d-maltosyl-beta cyclodextrin. PMID- 28985022 TI - Endocrine sensitivity of estrogen receptor-positive breast cancer is negatively correlated with aspartate-beta-hydroxylase expression. AB - Although prognostic markers for early estrogen receptor (ER)-positive breast cancer have been extensively developed, predictive markers for adjuvant endocrine therapy are still lacking. Focusing on the mechanisms underlying endocrine resistance, we investigated whether the endocrine sensitivity of ER-positive breast cancer cells was correlated with the expression of aspartate-beta hydroxylase (ASPH), which is involved in the development of hepatocellular carcinoma. ASPH expression in ER-positive and tamoxifen-resistant breast cancer cells was upregulated by the MAPK and phosphoinositide-3 kinase (PI3K) pathways, which both play pivotal roles in endocrine resistance. In the clinical setting, ASPH expression was negatively correlated with recurrence-free survival of luminal B breast cancer patients that received adjuvant endocrine therapy, but not in patients that did not receive adjuvant endocrine therapy. Luminal B breast cancer is one of the intrinsic molecular subtypes identified by the Prediction Analysis of Microarray 50 (PAM50) multiple gene classifier, and because of its poor response to endocrine therapy, chemotherapy in addition to endocrine therapy is generally required after surgical resection. Our results suggest that the endocrine sensitivity of luminal B breast cancer can be assessed by examining ASPH expression, which promotes the consideration of a prospective study on the association between ASPH expression at the mRNA and protein levels in luminal B breast cancer and subsequent response to endocrine therapy. PMID- 28985026 TI - Urologic malignancies in kidney transplantation. AB - With advances in immunosuppression, graft and patient outcomes after kidney transplantation have improved considerably. As a result, long-term complications of transplantation, such as urologic malignancies, have become increasingly important. Kidney transplant recipients, for example, have a 7-fold risk of renal cell carcinoma (RCC) and 3-fold risk of urothelial carcinoma (UC) compared with the general population. While extrapolation of data from the general population suggest that routine cancer screening in transplant recipients would allow for earlier diagnosis and management of these potentially lethal malignancies, currently there is no consensus for posttransplantation RCC or UC screening as supporting data are limited. Further understanding of risk factors, presentation, optimal management of, and screening for urologic malignancies in kidney transplant patients is warranted, and as such, this review will focus on the incidence, surveillance, and treatment of urologic malignancies in kidney transplant recipients. PMID- 28985027 TI - A Copper-Catalyzed Aerobic [1,3]-Nitrogen Shift through Nitrogen-Radical 4-exo trig Cyclization. AB - A novel radical [1,3]-nitrogen shift catalyzed by copper diacetate under an oxygen atmosphere (1 atm) has been developed for the construction of a diverse range of indole derivatives from alpha,alpha-disubstituted benzylamine. In this reaction, oxygen was used as a clean terminal oxidant, and water was produced as the only by-product. Five inert bonds were cleaved, and two C-N bonds and one C-C double bond were constructed in one pot during this transformation. This unique method demonstrated broad application protential for the late-stage modification of biologically active natural products and drugs. Mechanistic investigations indicate that a unique 4-exo-trig cyclization of an aminyl radical onto a phenyl ring is involved in the catalytic cycle. PMID- 28985028 TI - Pitfalls in using fluorescence tagging of nanomaterials: tecto-dendrimers in skin tissue as investigated by Cluster-FLIM. AB - Targeted topical application promises high drug concentrations in the skin and low systemic adverse effects. To locate drugs and drug-delivery systems like nanocarriers, fluorescent dyes are commonly used as drug surrogates or nanocarrier labels in micrographs of tissue sections. Here, we investigate how labeling degree, concentration of fluorophore, and nanocarrier may affect the interpretation of these micrographs. False-negative penetration results due to inter- and intramolecular quenching effects are likely. Using tecto-dendrimers as an example, we present a detailed analysis of pitfalls in the (semi-)quantitative evaluation of skin nanocarrier penetration. Fluorescence lifetime imaging microscopy (FLIM) allows distinguishing the target fluorescence of dye-tagged nanocarriers from skin autofluorescence, providing a highly sensitive tool for clear-cut localization of the nanocarriers. Cluster-FLIM images reveal that FITC labeled tecto-dendrimers penetrate the stratum corneum of human skin ex vivo and reconstructed human skin but do not cross the tight junction barrier. PMID- 28985025 TI - Multidisciplinary approach to cardiac and pulmonary vascular disease risk assessment in liver transplantation: An evaluation of the evidence and consensus recommendations. AB - Liver transplant (LT) candidates today are older, have greater medical severity of illness, and have more cardiovascular comorbidities than ever before. In addition, there are specific cardiovascular responses in cirrhosis that can be detrimental to the LT candidate. Cirrhotic cardiomyopathy, a condition characterized by increased cardiac output and a reduced ventricular response to stress, is present in up to 30% of patients with cirrhosis, thus challenging perioperative management. Current noninvasive tests that assess for subclinical coronary and myocardial disease have low sensitivity, and altered hemodynamics during the LT surgery can unmask latent cardiovascular disease either intraoperatively or in the immediate postoperative period. Therefore, this review, assembled by a group of multidisciplinary experts in the field and endorsed by the American Society of Transplantation Liver and Intestine and Thoracic and Critical Care Communities of Practice, provides a critical assessment of the diagnosis of cardiac and pulmonary vascular disease and interventions aimed at managing these conditions in LT candidates. Key points and practice-based recommendations for the diagnosis and management of cardiac and pulmonary vascular disease in this population are provided to offer guidance for clinicians and identify gaps in knowledge for future investigations. PMID- 28985029 TI - A variant associated with sagittal nonsyndromic craniosynostosis alters the regulatory function of a non-coding element. AB - Craniosynostosis presents either as a nonsyndromic congenital anomaly or as a finding in nearly 200 genetic syndromes. Our previous genome-wide association study of sagittal nonsyndromic craniosynostosis identified associations with variants downstream from BMP2 and intronic in BBS9. Because no coding variants in BMP2 were identified, we hypothesized that conserved non-coding regulatory elements may alter BMP2 expression. In order to identify and characterize noncoding regulatory elements near BMP2, two conserved noncoding regions near the associated region on chromosome 20 were tested for regulatory activity with a Renilla luciferase assay. For a 711 base pair noncoding fragment encompassing the most strongly associated variant, rs1884302, the luciferase assay showed that the risk allele (C) of rs1884302 drives higher expression of the reporter than the common allele (T). When this same DNA fragment was tested in zebrafish transgenesis studies, a strikingly different expression pattern of the green fluorescent reporter was observed depending on whether the transgenic fish had the risk (C) or the common (T) allele at rs1884302. The in vitro results suggest that altered BMP2 regulatory function at rs1884302 may contribute to the etiology of sagittal nonsyndromic craniosynostosis. The in vivo results indicate that differences in regulatory activity depend on the presence of a C or T allele at rs1884302. PMID- 28985030 TI - A double-edged sword: The world according to Capicua in cancer. AB - CIC/Capicua is an HMG-box transcription factor that is well conserved during evolution. CIC recognizes the T(G/C)AATG(A/G)A sequence and represses its target genes, such as PEA3 family genes. The receptor tyrosine kinase/RAS/MAPK signals downregulate CIC and relieves CIC's target genes from the transrepressional activity; CIC thus acts as an important downstream molecule of the pathway and as a tumor suppressor. CIC loss-of-function mutations are frequently observed in several human neoplasms such as oligodendroglioma, and lung and gastric carcinoma. CIC is also involved in chromosomal translocation-associated gene fusions in highly aggressive small round cell sarcoma that is biologically and clinically distinct from Ewing sarcoma. In these mutations, PEA3 family genes and other important target genes are upregulated, inducing malignant phenotypes. Downregulation of CIC abrogates the effect of MAPK inhibitors, suggesting its potential role as an important modifier of molecular target therapies for cancer. These data reveal the importance of CIC as a key molecule in signal transduction, carcinogenesis, and developing novel therapies. PMID- 28985031 TI - Trends in sinusitis research: a systematic review of extramural funding. AB - BACKGROUND: Innovation represents a core value of the American Rhinologic Society (ARS), with multiple efforts to promote research in the advancement rhinologic care. We therefore sought to identify trends in extramural sinusitis funding and underutilized sources of support to facilitate future efforts. METHODS: A systematic review of the National Institutes of Health (NIH) Research Portfolio Online Tools (RePORTER) database (fiscal year 1993 to 2017) was completed with the search strategy: ("chronic sinusitis" OR rhinosinusitis). All identified studies were accepted for review, with comparison to ARS membership rolls to identify studies supported by ARS investigators. Foundation awards were surveyed to identify and characterize additional sources of support. RESULTS: The systematic review identified 958 projects receiving NIH funding, of which 120 remain active. The percentage of sinusitis-related awards and total funding relative to all NIH awards increased over the past 10 years (2006 to 2016) from 0.06% (8 / 9128) and 0.09% ($2,151,152 / $3,358,338,602) to 0.87% (86 / 9540) and 0.90% ($37,201,095 / $4,300,145,614). Among active studies, 9 investigators maintain membership in the ARS and serve as principal investigator or project leader in 12 (10%) studies. ARS investigators received the greatest number of awards from the National Institute on Deafness and Other Communication Disrders (n = 8,66.7%), while only receiving 2.2% of awarded funding from the National Institute of Allergy and Infectious Diseases ($607,500/$26,873,022), the largest source of awards for sinusitis research. CONCLUSION: Support for sinusitis research is significantly growing, with the largest source of active funding not being fully utilized by members of the ARS. Further efforts to promote funding priorities among extramural sources is necessary to facilitate increased funding for ARS member initiatives. PMID- 28985032 TI - Organ-on-a-Chip Systems for Women's Health Applications. AB - Biomedical research, for a long time, has paid little attention to the influence of sex in many areas of study, ranging from molecular and cellular biology to animal models and clinical studies on human subjects. Many studies solely rely on male cells/tissues/animals/humans, although there are profound differences in male and female physiology, which can significantly impact disease mechanisms, toxicity of compounds, and efficacy of pharmaceuticals. In vitro systems have been traditionally very limited in their capacity to recapitulate female-specific physiology and anatomy such as dynamic sex-hormone levels and the complex interdependencies of female reproductive tract organs. However, the advent of microphysiological organ-on-a-chip systems, which attempt to recreate the 3D structure and function of human organs, now gives researchers the opportunity to integrate cells and tissues from a variety of individuals. Moreover, adding a dynamic flow environment allows mimicking endocrine signaling during the menstrual cycle and pregnancy, as well as providing a controlled microfluidic environment for pharmacokinetic modeling. This review gives an introduction into preclinical and clinical research on women's health and discusses where organ-on a-chip systems are already utilized or have the potential to deliver new insights and enable entirely new types of studies. PMID- 28985035 TI - Tumor-associated myeloid cells: new understandings on their metabolic regulation and their influence in cancer immunotherapy. AB - Tumor-associated myeloid cells (TAMCs), mainly represented by tumor-associated macrophages and myeloid-derived suppressor cells, can promote tumor growth directly, by favoring tumor cell proliferation and survival, and indirectly, by creating an immunosuppressive microenvironment. Myeloid cells are characterized by an extreme phenotypical and functional plasticity. Immunometabolism is now emerging as a crucial aspect of TAMCs skewing toward pro-tumoral activities. The metabolic re-education of myeloid cells is a new strategy to boost their antitumor effector functions. Several anticancer therapies targeting TAMCs are already under investigation. Nowadays, the hot topic of cancer immunotherapy is represented by immune checkpoint inhibitors. These drugs unrestrain T-cell mediated tumor elimination by removing suppressive signals delivered by tumor associated cells. The efficacy of immune checkpoint blockade can be enhanced using coordinated strategies to counteract the TAMCs-dependent impairment of immune adaptive responses. In the first part of the review, we will describe the association between metabolic reprogramming and TAMCs biological activities. In the second part, we will illustrate the potential of combination therapies associating TAMC-targeting drugs with immune checkpoint inhibitors. PMID- 28985033 TI - Associations of Maternal Weight Status Before, During, and After Pregnancy with Inflammatory Markers in Breast Milk. AB - OBJECTIVE: The goal of this study was to examine the associations of maternal weight status before, during, and after pregnancy with breast milk C-reactive protein (CRP) and interleukin 6 (IL-6), two bioactive markers of inflammation, measured at 1 and 3 months post partum. METHODS: Participants were 134 exclusively breastfeeding mother-infant dyads taking part in the Mothers and Infants Linked for Health (MILK) study, who provided breast milk samples. Pre pregnancy body mass index (BMI) and gestational weight gain (GWG) were assessed by chart abstraction; postpartum weight loss was measured at the 1- and 3-month study visits. Linear regression was used to examine the associations of maternal weight status with repeated measures of breast milk CRP and IL-6 at 1 and 3 months, after adjustment for potential confounders. RESULTS: Pre-pregnancy BMI and excessive GWG, but not total GWG or postpartum weight loss, were independently associated with breast milk CRP after adjustment (beta = 0.49, P < 0.001 and beta = 0.51, P = 0.011, respectively). No associations were observed for IL-6. CONCLUSIONS: High pre-pregnancy BMI and excessive GWG are associated with elevated levels of breast milk CRP. The consequences of infants receiving varying concentrations of breast milk inflammatory markers are unknown; however, it is speculated that there are implications for the intergenerational transmission of disease risk. PMID- 28985034 TI - Esophageal adenocarcinoma microenvironment: Peritumoral adipose tissue effects associated with chemoresistance. AB - Peritumoral microenvironment affects cancer development and chemoresistance, and visceral adipose tissue may play a critical role. We aimed to identify depot specific adipose characteristics associated with carcinogenesis and resistance to neoadjuvant therapy in esophageal adenocarcinoma (EAC). We analyzed: (i) the peritumoral adipose tissue of rats following the induction of esophageal carcinogenesis; (ii) the peritumoral and distal (omental) adipose tissue of patients affected by EAC; (iii) adipose-derived stem cells (ADSC) isolated from healthy patients and treated with conditioned medium (CM), collected from tumoral and adipose tissue of patients with EAC. In peritumoral adipose tissue of rats, CD34, CD31 and vascular endothelial growth factor (VEGF) expression increased progressively during EAC development. In patients with EAC, expression of CD34, CD45, CD90 and nucleostemin (NSTM) was higher in peritumoral than in distal adipose tissue and decreased in the presence of neoadjuvant therapy. Moreover, expression of NSTM, octamer-binding transcription factor 4 (OCT-4) and VEGF was higher in peritumoral (but not in distal) adipose tissue of chemoresistant patients. In ADSC, treatment with peritumoral adipose tissue CM increased the adipogenic potential and the expression of CD34, CD90, NSTM and OCT-4. These effects were similar to those induced by cancer-derived CM, but were not observed in ADSC treated with distal adipose tissue CM and were partially reduced by a leptin antagonist. Last, ADSC treated with peritumoral CM of chemoresistant patients displayed increased expression of NSTM, OCT-4, leptin, leptin receptor, alpha-smooth muscle actin (alpha-SMA), CD34 and VEGF. These results suggest that peritumoral adipose tissue may promote, by paracrine signaling, the expression of depot-specific factors associated with therapeutic resistance. PMID- 28985036 TI - Preparation of a long-alkyl-chain-based hybrid monolithic column with mixed-mode interactions using a "one-pot" process for pressurized capillary electrochromatography. AB - A simple "one-pot" approach for the preparation of a new vinyl-functionalized organic-inorganic hybrid monolithic column is described. In this improved method, the hydrolyzed alkoxysilanes of tetramethoxysilane and triethoxyvinylsilane were used as precursors for the synthesis of a silica-based monolith, while 1 hexadecene and sodium ethylenesulfonate were used as vinyl functional monomers along with azobisisobutyronitrile as an initiator. The effects of reaction temperature, urea content, and composition of organic monomers on the column properties (e.g. morphology, mechanical stability, and chromatographic performance) were investigated. The monolithic column was used for the separation of neutral solutes by reversed-phase pressurized capillary. Furthermore, the monolith can separate various aromatic amines, which indicated its excellent cation-exchange capability and hydrophobic interactions. The baseline separation of the aromatic amines was obtained with a column efficiency of up to 78 000 plates/m. PMID- 28985038 TI - Characterizing biochemical and morphological variations of clinically relevant anatomical locations of oral tissue in vivo with hybrid Raman spectroscopy and optical coherence tomography technique. AB - This study aims to characterize biochemical and morphological variations of the clinically relevant anatomical locations of in vivo oral tissue (ie, alveolar process, lateral tongue and floor of the mouth) by using hybrid Raman spectroscopy (RS) and optical coherence tomography (OCT) technique. A total of 1049 in vivo fingerprint (FP: 800-1800 cm-1 ) and high wavenumber (HW: 2800-3600 cm-1 ) Raman spectra were acquired from different oral tissue (alveolar process = 331, lateral tongue = 339 and floor of mouth = 379) of 26 normal subjects in the oral cavity under the OCT imaging guidance. The total Raman dataset were split into 2 parts: 80% for training and 20% for testing. Tissue optical attenuation coefficients of alveolar process, lateral tongue and the floor of the mouth were derived from OCT images, revealing the inter-anatomical morphological differences; while RS uncovers subtle FP/HW Raman spectral differences among different oral tissues that can be attributed to the differences in inter- and intra-cellular proteins, lipids, DNA and water structures and conformations, enlightening biochemical variability of different oral tissues at the molecular level. Partial least squares-discriminant analysis implemented on the training dataset show that the integrated tissue optical attenuation coefficients and FP/HW Raman spectra provide diagnostic sensitivities of 99.6%, 82.3%, 50.2%, and specificities of 97.0%, 75.1%, 92.1%, respectively, which are superior to using either RS (sensitivities of 90.2%, 77.5%, 48.8%, and specificities of 95.8%, 72.1%, 88.8%) or optical attenuation coefficients derived from OCT (sensitivities of 75.0%, 78.2%, 47.2%, and specificities of 96.2%, 67.7%, 85.0%) for the differentiation among alveolar process, lateral tongue and the floor of the mouth. Furthermore, the diagnostic algorithms applied to the independent testing dataset based on hybrid RS-OCT technique gives predictive diagnostic sensitivities of 100%, 76.5%, 51.3%, and specificities of 95.1%, 77.6%, 89.6%, respectively, for the classifications among alveolar process, lateral tongue and the floor of the mouth, which performs much better than either RS or optical attenuation coefficient derived from OCT imaging. This work suggests that inter anatomical morphological and biochemical variability are significant which should be considered as an important parameter in the interpretation and rendering of hybrid RS-OCT technique for oral tissue diagnosis and characterization. PMID- 28985037 TI - Postoperative sinonasal morbidity in sellar reconstruction: mucosal autograft versus acellular dermal allograft. AB - BACKGROUND: Sellar pathology is increasingly addressed using the expanded endonasal approach (EEA). Although avascular graft reconstruction is an acceptable means to prevent cerebrospinal fluid leak, there are few data regarding sinonasal morbidity in these patients. In this study we compare rates of persistent postoperative crusting (PPC) and rhinosinusitis in patients undergoing sellar reconstruction with mucosal autografting and acellular dermal allografting (ADA). METHODS: Patients undergoing the EEA between 2008 and 2014 were categorized into 2 subgroups: mucosal reconstruction and ADA reconstruction. Univariate analyses were performed to compare differences in PPC and rhinosinusitis in these groups and to identify risk factors for sinonasal morbidity. Multivariate propensity matching analysis was performed to match ADA and mucosa reconstruction groups with respect to age, race, gender, smoking status, diabetes status, tumor type, tumor size, and revision vs primary surgery. RESULTS: A total of 149 patients were identified. There were 105 patients reconstructed with autologous mucosa (70.5%) and 44 reconstructed with ADA (29.5%). Overall, PPC was seen in 20 patients (13.4%) and rhinosinusitis in 10 patients (6.7%). Propensity matching generated 39 patients reconstructed with ADA and 39 reconstructed with mucosa. There was a significant increase in PPC in patients reconstructed with ADA compared to those reconstructed with mucosa (8 of 39 [20.5%] vs 2 of 39 [5.1%], p = 0.04). There was no association between reconstruction with ADA and increased rhinosinusitis (3 of 39 [7.7%] vs 4 of 39 [10.3%], p = 0.64). CONCLUSION: Sinonasal morbidity is not uncommon after sellar reconstruction. Patients undergoing sellar reconstruction with ADA may be at increased risk of postoperative crusting compared with those undergoing reconstruction with mucosa. PMID- 28985039 TI - Pretreatment Fasting Plasma Glucose Modifies Dietary Weight Loss Maintenance Success: Results from a Stratified RCT. AB - OBJECTIVE: Levels of fasting plasma glucose (FPG) and fasting insulin (FI) were studied as diet-specific prognostic markers for successful weight loss maintenance in participants with overweight. METHODS: After losing >= 8% of body weight, participants received one of three ad libitum diets for 6 months: (1) a moderate-fat diet high in monounsaturated fatty acids (MUFA); a low-fat, high fiber diet (Nordic Nutrition Recommendations [NNR]); and the Average Danish Diet (ADD). Participants were categorized as having low (< 90 mg/dL) or high (90-105 mg/dL) FPG based on preintervention values. Median FI among those having high FPG was used as a cutoff for FI (FI <= 50 pmol/L; FI > 50 pmol/L). RESULTS: Participants with low FPG and randomized to MUFA, NNR, and ADD regained similarly 2.1 to 2.5 kg after 6 months. By contrast, participants with high FPG and randomized to MUFA, NNR, and ADD regained 2.73 kg (95% CI 1.33 to 4.13; P < 0.001), -0.05 kg (95% CI -1.95 to 1.86; P = 0.96), and 4.16 kg (95% CI 2.27 to 6.06; P < 0.001) after 6 months, respectively, resulting in lower weight regain on NNR compared to ADD (-4.21 kg [95% CI -6.83 to -1.59]; P = 0.002) and MUFA (95% CI -2.77 kg [-5.12 to -0.43]; P = 0.020). The addition of FI strengthened these associations. CONCLUSIONS: Slightly elevated pretreatment FPG determined success in dietary weight loss maintenance among overweight patients on ad libitum diets differing in macronutrient and fiber content. PMID- 28985040 TI - Comparison of Methods for Analyzing Human Adipose Tissue Macrophage Content. AB - OBJECTIVE: The relationship between inflammation, obesity, and adverse metabolic conditions is associated with adipose tissue macrophages (ATM). This study compared the measurements of human ATM using flow cytometry, immunohistochemistry (IHC), and real-time polymerase chain reaction (RT-PCR) of ATM markers. METHODS: A new software program (AMCounter) was evaluated to help measure ATM using IHC, and this was compared to flow cytometry and RT-PCR. RESULTS: IHC had good intraindividual reproducibility for total (CD68), proinflammatory (CD14), and anti-inflammatory (CD206) ATM. The AMCounter improved interreader agreement and was more time efficient. Flow cytometry had acceptable intraindividual reproducibility for the percentage of CD68+ cells that were CD14+ or CD206+ , but not for ATMs per gram of tissue. ATMs per gram of tissue was much greater using IHC than flow cytometry. The flow cytometry and IHC measures of ATM from the same biopsies were not correlated. There were statistically significant correlations between RT-PCR CD68 and IHC CD68, CD14, and CD206 ATMs per 100 adipocytes. Also of interest were statistically significant correlations between RT-PCR CD68 and IHC CD68, CD14, and adipose flow cytometry measures of CD68+ , CD68+ /CD14+ , and CD68+ /CD206+ ATMs per gram of tissue. CONCLUSIONS: The AMCounter software helps provide reproducible and efficient measures of IHC ATMs. Flow cytometry, IHC, and RT-PCR measures of adipose inflammation provide somewhat different information. PMID- 28985042 TI - IVF in Costa Rica. AB - For 16 years, Costa Rica was the only country in the world that banned IVF, after it had been successfully conducted from 1995 to 2000. It also has been the only country that banned IVF based on the argument that it protects the embryo. After years of conflict, the prohibition has finally been lifted and the first baby girl was born in March 2017. This paper recounts the judicial and legal struggles Costa Rica faced in order to reestablished its IVF program. PMID- 28985041 TI - Influence of the abstinence period on human sperm quality: analysis of 2,458 semen samples. AB - OBJECTIVE: The aim of this study was to evaluate the influence of different periods of abstinence on conventional semen parameters as well as functional parameters in human semen, including mitochondrial function, chromatin packing and sperm DNA fragmentation. METHODS: We recruited a cohort of 2,458 men undergoing infertility investigation. Semen analyses were performed according to WHO guidelines/morphology-motile sperm organelle morphology examination/MSOME. For DNA integrity analysis, the percentages of DNA fragmentation (TUNEL), abnormal chromatin packaging/underprotamination (chromomycin A3/CMA3), abnormal mitochondrial membrane potential (MMP/MitoTracker Green), and apoptosis (annexin V) were recorded. Associations between the sexual abstinence period and sperm parameters were assessed using Spearman correlation. For group comparisons, the subjects were categorized according to the sexual abstinence period (SAP) into three groups: SAP <2 days, SAP 2-5 days, and SAP >5 days. RESULTS: The duration of abstinence had a statistically significant positive influence on sperm concentration and volume, the number of leukocytes and a statistically significant negative influence on sperm motility and vitality. The percentages of DNA fragmentation and MMP (mitochondrial damage) worsened with the increased duration of abstinence. The percentage of sperm protamination was statistically significantly increased with abstinence. CONCLUSION: Increase in the sexual abstinence period influences sperm quality. This study reinforces the importance of the duration of ejaculatory abstinence on semen parameter variation. It highlights the deleterious effect of increased abstinence on DNA damage, which is most likely associated with ROS (mitochondrial damage/number of leukocytes). The increase in chromatin packaging can represent a protective feature for DNA. PMID- 28985043 TI - Is There a Cholinergic Survival Incentive for Neurotropic Parasites in the Brain? AB - The reason why some parasites specifically target the brain remains a mystery. Often, it is seen that the primary site of infection is quite remote from the brain, but an eventual involvement of the cerebral tissue is seen to occur that becomes the cause of death of the majority of the patients. In the absence of a clear preferential reason for targeting the brain, chemicals produced by the nervous system, which have miniature concentrations in the blood, appear to set up a chemical attraction that eventually causes them to migrate to the neural tissue. We studied the possible chemicals of neural origin that can lure the parasite toward the brain, enabling them to cause meningoencephalitis. The identification of these chemicals could be of enormous prophylactic significance as blocking the chemotaxis of neurotropic parasite by antagonist drugs and chemicals can prevent cerebral infection and provide ample time to eradicate the parasites at the primary site of infection. PMID- 28985044 TI - Biosynthesis of (-)-5-Hydroxy-equol and 5-Hydroxy-dehydroequol from Soy Isoflavone, Genistein Using Microbial Whole Cell Bioconversion. AB - Equols are isoflavandiols formed by reduction of soy isoflavones such as daidzein and genistein by gut microorganisms. These phytoestrogens are of interest for their various biological effects. We report biosynthesis from genistein to (-)-5 hydroxy-equol in recombinant E. coli expressing three reductases (daidzein reductase DZNR, dihidrodaidzein reductase DHDR, tetrahydrodaidzein reductase THDR) and a racemase (dihydrodaidzein racemase, DDRC) originating from the gut bacterium, Slackia isoflavoniconvertens. The biosynthesized 5-hydroxy-equol proved as an optically negative enantiomer, nonetheless it displayed an inverse circular dichroism spectrum to (S)-equol. Compartmentalized expression of DZNR and DDRC in one E. coli strain and DHDR and THDR in another increased the yield to 230 mg/L and the productivity to 38 mg/L/h. If the last reductase was missing, the intermediate spontaneously dehydrated to 5-hydroxy-dehydroequol in up to 99 mg/L yield. This novel isoflavene, previously not known to be synthesized in nature, was also detected in this biotransformation system. Although (S)-equol favors binding to human estrogen receptor (hER) beta over hERalpha, (-)-5-hydroxy equol showed the opposite preference. This study provides elucidation of the biosynthetic route of (-)-5-hydroxy-equol and measurement of its potent antagonistic character as a phytoestrogen for the first time. PMID- 28985045 TI - Microwave-Assisted Regioselective Synthesis of 3-Functionalized Indole Derivatives via Three-Component Domino Reaction. AB - A microwave-assisted regioselective synthesis of 3-functionalized indole derivatives via a three-component domino reaction of anilines, arylglyoxal monohydrates, and cyclic 1,3-dicarbonyl compounds is described. The main advantages of this protocol are short reaction times, practical simplicity, its metal-free nature, the availability of starting materials, green solvents, and high regioselectivity. PMID- 28985046 TI - Self-Supported Hierarchical FeCoNi-LTH/NiCo2O4/CC Electrodes with Enhanced Bifunctional Performance for Efficient Overall Water Splitting. AB - The development of advanced earth-abundant electrocatalysts for hydrogen production is highly desirable. In this paper, we report the design and synthesis of a novel and highly efficient electrode of NiCo2O4 nanoneedles decorated with FeCoNi layered ternary hydroxides supported on carbon cloth (FeCoNi LTH/NiCo2O4/CC) by a facile and efficient two-step approach. It exhibits superior bifunctional catalytic activities for the oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) in alkaline media, due to the special structure and strong synergies. The FeCoNi-LTH/NiCo2O4/CC obtains an onset overpotential of 240 mV and an overpotential of 302 mV at the current density of 50 mA cm-2 for OER, which is superior to RuO2. It also efficiently catalyzes HER with onset overpotential of 96 mV and overpotential of 151 mV to achieve a current density of 20 mA cm-2. Serving as both cathode and anode in a two-electrode water splitting system, FeCoNi-LTH/NiCo2O4/CC only requires an overpotential of 1.65 V at current density of 50 mA cm-2. The cell exhibits outstanding stability as well, indicating that FeCoNi-LTH/NiCo2O4/CC is a befitting material to be utilized as effective bifunctional catalysts for overall water splitting. PMID- 28985047 TI - Direct Organization of Morphology-Controllable Mesoporous SnO2 Using Amphiphilic Graft Copolymer for Gas-Sensing Applications. AB - A simple and flexible strategy for controlled synthesis of mesoporous metal oxide films using an amphiphilic graft copolymer as sacrificial template is presented and the effectiveness of this approach for gas-sensing applications is reported. The amphiphilic graft copolymer poly(vinyl chloride)-g-poly(oxyethylene methacrylate) (PVC-g-POEM) is used as a sacrificial template for the direct synthesis of mesoporous SnO2. The graft copolymer self-assembly is shown to enable good control over the morphology of the resulting SnO2 layer. Using this approach, mesoporous SnO2 based sensors with varied porosity are fabricated in situ on a microheater platform. This method reduces the interfacial contact resistance between the chemically sensitive materials and the microheater, while a simple fabrication process is provided. The sensors show significantly different gas-sensing performances depending on the SnO2 porosity, with the highly mesoporous SnO2 sensor exhibiting high sensitivity, low detection limit, and fast response and recovery toward hydrogen gas. This printable solution-based method can be used reproducibly to fabricate a variety of mesoporous metal oxide layers with tunable morphologies on various substrates for high-performance applications. PMID- 28985048 TI - Homogeneous Catalysis for Sustainable Hydrogen Storage in Formic Acid and Alcohols. AB - Hydrogen gas is a storable form of chemical energy that could complement intermittent renewable energy conversion. One of the main disadvantages of hydrogen gas arises from its low density, and therefore, efficient handling and storage methods are key factors that need to be addressed to realize a hydrogen based economy. Storage systems based on liquids, in particular, formic acid and alcohols, are highly attractive hydrogen carriers as they can be made from CO2 or other renewable materials, they can be used in stationary power storage units such as hydrogen filling stations, and they can be used directly as transportation fuels. However, to bring about a paradigm change in our energy infrastructure, efficient catalytic processes that release the hydrogen from these molecules, as well as catalysts that regenerate these molecules from CO2 and hydrogen, are required. In this review, we describe the considerable progress that has been made in homogeneous catalysis for these critical reactions, namely, the hydrogenation of CO2 to formic acid and methanol and the reverse dehydrogenation reactions. The dehydrogenation of higher alcohols available from renewable feedstocks is also described. Key structural features of the catalysts are analyzed, as is the role of additives, which are required in many systems. Particular attention is paid to advances in sustainable catalytic processes, especially to additive-free processes and catalysts based on Earth-abundant metal ions. Mechanistic information is also presented, and it is hoped that this review not only provides an account of the state of the art in the field but also offers insights into how superior catalytic systems can be obtained in the future. PMID- 28985049 TI - Themis: Batch Preprocessing for Ultrahigh-Resolution Mass Spectra of Complex Mixtures. AB - Fourier transform ion cyclotron resonance mass spectrometry affords the resolving power to determine an unprecedented number of components in complex mixtures, such as petroleum. The software tools required to also analyze these data struggle to keep pace with advancing instrument capabilities and increasing quantities of data, particularly in terms of combining information efficiently across multiple replicates. Improved confidence in data and the use of replicates is particularly important where strategic decisions will be based upon the analysis. We present a new algorithm named Themis, developed using R, to jointly preprocess replicate measurements of a sample with the aim of improving consistency as a preliminary step to assigning peaks to chemical compositions. The main features of the algorithm are quality control criteria to detect failed runs, ensuring comparable magnitudes across replicates, peak alignment, and the use of an adaptive mixture model-based strategy to help distinguish true peaks from noise. The algorithm outputs a list of peaks reliably observed across replicates and facilitates data handling by preprocessing all replicates in a single step. The processed data produced by our algorithm can subsequently be analyzed by use of relevant specialized software. While Themis has been demonstrated with petroleum as an example of a complex mixture, its basic framework will be useful for complex samples arising from a variety of other applications. PMID- 28985051 TI - Catalytic Paper Spray Ionization Mass Spectrometry with Metal Nanotubes and the Detection of 2,4,6-Trinitrotoluene. AB - Materials are making inroads into mass spectrometry, and an example is the use of advanced materials for enhanced ionization by transformation of a less-ionizable molecule to an easily ionizable one. Here we show the use of Pt nanoparticle decorated nanotubes as highly active catalysts for the reduction of 2,4,6 trinitrotoluene to 2,4,6-triaminotoluene and subsequent easy detection of the product by in situ ambient ionization mass spectrometry. PMID- 28985050 TI - Parallel Synthesis of 1H-Pyrazolo[3,4-d]pyrimidines via Condensation of N Pyrazolylamides and Nitriles. AB - A novel parallel medicinal chemistry (PMC)-enabled synthesis of 1H-pyrazolo[3,4 d]pyrimidines employing condensation of easily accessible N-pyrazolylamides and nitriles has been developed. The presented studies describe singleton and library enablements that allowed rapid generation of molecular diversity to examine C4 and C6 vectors. This chemistry enabled access to challenging alkyl substituents, expanding the overall chemical space beyond that available via typical C(sp2) C(sp2) coupling and SNAr transformations. Furthermore, monomer group interconversions allowing the use of larger and more diverse amides and carboxylic acids as precursors to nitriles are discussed. PMID- 28985052 TI - Hydrazinium Salt as Additive To Improve Film Morphology and Carrier Lifetime for High-Efficiency Planar-Heterojunction Perovskite Solar Cells via One-Step Method. AB - One-step solution process is the simplest method to fabricate organic-inorganic metal halide perovskite thin films, which however does not work well when employed in the planar-heterojunction (PHJ) solar cells due to the generally poor film morphology. Here we show that hydrazinium chloride can be used as an additive in the precursor solution to produce perovskite films featuring higher coverage and better crystallinity. The light absorption ability and charge carrier lifetime are both significantly improved accordingly. Under the optimal additive ratio, the average power conversion efficiency (PCE) of the inverted PHJ perovskite solar cells greatly increases by as much as 70%, and the champion device shows a satisfying PCE of 12.66%. These results suggest that N2H5Cl is a promising additive for fabricating high-efficiency perovskite solar cells via one step method, which could be of interest in the future commercial solar cell industry. PMID- 28985054 TI - Efficient Suppression of Defects and Charge Trapping in High Density In-Sn-Zn-O Thin Film Transistor Prepared using Microwave-Assisted Sputter. AB - Amorphous oxide semiconductor-based thin film transistors (TFTs) have been considered as excellent switching elements for driving active-matrix organic light-emitting diodes (AMOLED) owing to their high mobility and process compatibility. However, oxide semiconductors have inherent defects, causing fast transient charge trapping and device instability. For the next-generation displays such as flexible, wearable, or transparent displays, an active semiconductor layer with ultrahigh mobility and high reliability at low deposition temperature is required. Therefore, we introduced high density plasma microwave-assisted (MWA) sputtering method as a promising deposition tool for the formation of high density and high-performance oxide semiconductor films. In this paper, we present the effect of the MWA sputtering method on the defects and fast charge trapping in In-Sn-Zn-O (ITZO) TFTs using various AC device characterization methodologies including fast I-V, pulsed I-V, transient current, low frequency noise, and discharge current analysis. Using these methods, we were able to analyze the charge trapping mechanism and intrinsic electrical characteristics, and extract the subgap density of the states of oxide TFTs quantitatively. In comparison to conventional sputtered ITZO, high density plasma MWA-sputtered ITZO exhibits outstanding electrical performance, negligible charge trapping characteristics and low subgap density of states. High-density plasma MWA sputtering method has high deposition rate even at low working pressure and control the ion bombardment energy, resulting in forming low defect generation in ITZO and presenting high performance ITZO TFT. We expect the proposed high density plasma sputtering method to be applicable to a wide range of oxide semiconductor device applications. PMID- 28985053 TI - Structural and Functional Characterization of Malate Synthase G from Opportunistic Pathogen Pseudomonas aeruginosa. AB - Pseudomonas aeruginosa is an opportunistic human pathogen recognized as a critical threat by the World Health Organization because of the dwindling number of effective therapies available to treat infections. Over the past decade, it has become apparent that the glyoxylate shunt plays a vital role in sustaining P. aeruginosa during infection scenarios. The glyoxylate shunt comprises two enzymes: isocitrate lyase and malate synthase isoform G. Inactivation of these enzymes has been reported to abolish the ability of P. aeruginosa to establish infection in a mammalian model system, yet we still lack the structural information to support drug design efforts. In this work, we describe the first X ray crystal structure of P. aeruginosa malate synthase G in the apo form at 1.62 A resolution. The enzyme is a monomer composed of four domains and is highly conserved with homologues found in other clinically relevant microorganisms. It is also dependent on Mg2+ for catalysis. Metal ion binding led to a change in the intrinsic fluorescence of the protein, allowing us to quantitate its affinity for Mg2+. We also identified putative drug binding sites in malate synthase G using computational analysis and, because of the high resolution of the experimental data, were further able to characterize its hydration properties. Our data reveal two promising binding pockets in malate synthase G that may be exploited for drug design. PMID- 28985055 TI - Modeling the Effects of Interfacial Characteristics on Gas Permeation Behavior of Nanotube-Mixed Matrix Membranes. AB - Theoretical approaches that accurately predict the gas permeation behavior of nanotube-containing mixed matrix membranes (nanotube-MMMs) are scarce. This is mainly due to ignoring the effects of nanotube/matrix interfacial characteristics in the existing theories. In this paper, based on the analogy of thermal conduction in polymer composites containing nanotubes, we develop a model to describe gas permeation through nanotube-MMMs. Two new parameters, "interfacial thickness" (aint) and "interfacial permeation resistance" (Rint), are introduced to account for the role of nanotube/matrix interfacial interactions in the proposed model. The obtained values of aint, independent of the nature of the permeate gas, increased by increasing both the nanotubes aspect ratio and polymer nanotube interfacial strength. An excellent correlation between the values of aint and polymer-nanotube interaction parameters, chi, helped to accurately reproduce the existing experimental data from the literature without the need to resort to any adjustable parameter. The data includes 10 sets of CO2/CH4 permeation, 12 sets of CO2/N2 permeation, 3 sets of CO2/O2 permeation, and 2 sets of CO2/H2 permeation through different nanotube-MMMs. Moreover, the average absolute relative errors between the experimental data and the predicted values of the proposed model are very small (less than 5%) in comparison with those of the existing models in the literature. To the best of our knowledge, this is the first study where such a systematic comparison between model predictions and such extensive experimental data is presented. Finally, the new way of assessing gas permeation data presented in the current work would be a simple alternative to complex approaches that are usually utilized to estimate interfacial thickness in polymer composites. PMID- 28985056 TI - Backbone-Fluorinated 1,2,3-Triazole-Containing Dipeptide Surrogates. AB - The 1,2,3-triazole moiety can be incorporated as a peptide bond bioisostere to provide protease resistance in peptidomimetics. Herein, we report the synthesis of peptidomimetic building blocks containing backbone-fluorinated 1,4 disubstituted 1,2,3-triazole moieties. Synthetic protocols for the preparation of various Xaa-Gly dipeptide surrogates in the form of Xaa-psi[triazole]-F2Gly building blocks were established, and selected examples were introduced into the endogenous peptide opioid receptor ligand Leu-enkephalin as a model compound. PMID- 28985057 TI - Research on the Mechanism of Aggregation-Induced Emission through Supramolecular Metal-Organic Frameworks with Mechanoluminescent Properties and Application in Press-Jet Printing. AB - This study investigates the mechanism of AIE in the solid state through supramolecular metal-organic frameworks and mechanoluminescent materials for the first time. Herein, four novel differently substituted Schiff base building blocks, SB1-SB4, exhibit typical AIE properties with various fluorescence emissions from yellow to green. SB1-SB4 are linked through C-H...O hydrogen bonding interactions to construct supramolecular metal-organic frameworks (SMOFs): namely, SMOFSB1-SMOFSB4. Particularly, among these SMOFs, SMOFSB3 is observed to have micropores in the 3D supramolecular structure and exhibits mechanoluminescent properties (grinding). An emission turn-on mechanism occurs with destruction of micropores by grinding and blockage of intramolecular rotations of the methyl and acetonitrile in the micropores, resulting in emission turn-on in SMOFSB3. Single-crystal X-ray structures, powder X-ray diffraction, emission spectra at room temperature, temperature-dependent emission spectra, DFT calculations, and a charge separation hypothesis well demonstrate the emission turn-on mechanism, which is consistent with the mechanism of AIE. More importantly, the molecules demonstrated potential application for press-jet printing. PMID- 28985058 TI - Identification of a Novel 1,2,3,4-Tetrahydrobenzo[b][1,6]naphthyridine Analogue as a Potent Phosphodiesterase 5 Inhibitor with Improved Aqueous Solubility for the Treatment of Alzheimer's Disease. AB - Phosphodiesterase 5 (PDE5) hydrolyzes cyclic guanosine monophosphate (cGMP) leading to increased levels of the cAMP response element binding protein (CREB), a transcriptional factor involved with learning and memory processes. We previously reported potent quinoline-based PDE5 inhibitors (PDE5Is) for the treatment of Alzheimer's disease (AD). However, the low aqueous solubility rendered them undesirable drug candidates. Here we report a series of novel PDE5Is with two new scaffolds, 1,2,3,4-tetrahydrobenzo[b][1,6]naphthyridine and 2,3-dihydro-1H-pyrrolo[3,4-b]quinolin-1-one. Among them, compound 6c, 2-acetyl-10 ((3-chloro-4-methoxybenzyl)amino)-1,2,3,4-tetrahydrobenzo[b][1,6]naphthyridine-8 carbonitrile, the most potent compound, has an excellent in vitro IC50 (0.056 nM) and improved aqueous solubility as well as good efficacy in a mouse model of AD. Furthermore, we are proposing two plausible binding modes obtained through in silico docking, which provide insights into the structural basis of the activity of the two series of compounds reported herein. PMID- 28985059 TI - Elucidation of Binding Site and Chiral Specificity of Oxidovanadium Drugs with Lysozyme through Theoretical Calculations. AB - This study presents an implementation of the protein-ligand docking program GOLD and a generalizable method to predict the binding site and orientation of potential vanadium drugs. Particularly, theoretical methods were applied to the study of the interaction of two VIVO complexes with antidiabetic activity, [VIVO(pic)2(H2O)] and [VIVO(ma)2(H2O)], where pic is picolinate and ma is maltolate, with lysozyme (Lyz) for which electron paramagnetic resonance spectroscopy suggests the binding of the moieties VO(pic)2 and VO(ma)2 through a carboxylate group of an amino acid residue (Asp or Glu). The work is divided in three parts: (1) the generation of a new series of parameters in GOLD program for vanadium compounds and the validation of the method on five X-ray structures of VIVO and VV species bound to proteins; (2) the prediction of the binding site and enantiomeric preference of [VO(pic)2(H2O)] to lysozyme, for which the X-ray diffraction analysis displays the interaction of a unique isomer (i.e., OC-6-23 Delta) through Asp52 residue, and the subsequent refinement of the results with quantum mechanics/molecular mechanics methods; (3) the application of the same approach to the interaction of [VO(ma)2(H2O)] with lysozyme. The results show that convenient implementation of protein-ligand docking programs allows for satisfactorily reproducing X-ray structures of metal complexes that interact with only one coordination site with proteins and predicting with blind procedures relevant low-energy binding modes. The results also demonstrate that the combination of docking methods with spectroscopic data could represent a new tool to predict (metal complex)-protein interactions and have a general applicability in this field, including for paramagnetic species. PMID- 28985060 TI - Regioselective Termination Reagents for Ring-Opening Alkyne Metathesis Polymerization. AB - Alkyne cross-metathesis of molybdenum carbyne complex [TolC=Mo(OCCH3(CF3)2)3].DME with 2 equiv of functional ynamines or ynamides yields the primary cross metathesis product with high regioselectivity (>98%) along with a molybdenum metallacyclobutadiene complex. NMR and X-ray crystal structure analysis reveals that ynamides derived from 1-(phenylethynyl)pyrrolidin-2-one selectively cleave the propagating molybdenum species in the ring-opening alkyne metathesis polymerization (ROAMP) of ring-strained 3,8-dihexyloxy-5,6-dihydro-11,12 didehydrodibenzo[a,e][8]annulene and irreversibly deactivate the diamagnetic molybdenum metallacyclobutadiene complex through a multidentate chelate binding mode. The chain termination of living ROAMP with substituted ethynylpyrrolidin-2 ones selectively transfers a functional end-group to the polymer chain, giving access to telechelic polymers. This regioselective carbyne transfer strategy gives access to amphiphilic block copolymers through synthetic cascades of ROAMP followed by ring-opening polymerization of strained epsilon-caprolactone. PMID- 28985062 TI - Nucleofuge Generating Glycosidations by the Remote Activation of Hydroxybenzotriazolyl Glycosides. AB - Hydroxybenzotriazole is routinely used in peptide chemistry for reducing racemization due to the increased reactivity. In this article, very stable hydroxybenzotriazolyl glucosides were identified to undergo glycosidation. The reaction was hypothesized to go through the remote activation by the Tf2O at the N3-site of HOBt followed by the extrusion of the oxocarbenium ion that was attacked by the glycosyl acceptor. Further, equilibration of the zwitterionic benzotriazolyl species makes the leaving group noncompetitive and generates the nucleofuge that has been reconverted to the glycosyl donor. The reaction is mild, high yielding, fast and suitable for donors containing both C2-ethers and C2 esters as well. The regenerative-donor glycosidation strategy is promising as it enables us to regenerate the glycosyl donor for further utilization. The utility of the methodology for the oligosaccharide synthesis was demonstrated by the successful synthesis of the branched pentamannan core of the HIV1-gp120 complex. PMID- 28985061 TI - Mechanistic Insight into the Photocontrolled Cationic Polymerization of Vinyl Ethers. AB - The mechanism of the recently reported photocontrolled cationic polymerization of vinyl ethers was investigated using a variety of catalysts and chain-transfer agents (CTAs) as well as diverse spectroscopic and electrochemical analytical techniques. Our study revealed a complex activation step characterized by one electron oxidation of the CTA. This oxidation is followed by mesolytic cleavage of the resulting radical cation species, which leads to the generation of a reactive cation-this species initiates the polymerization of the vinyl ether monomer-and a dithiocarbamate radical that is likely in equilibrium with the corresponding thiuram disulfide dimer. Reversible addition-fragmentation type degenerative chain transfer contributes to the narrow dispersities and control over chain growth observed under these conditions. Finally, the deactivation step is contingent upon the oxidation of the reduced photocatalyst by the dithiocarbamate radical concomitant with the production of a dithiocarbamate anion that caps the polymer chain end. The fine-tuning of the electronic properties and redox potentials of the photocatalyst in both the excited and the ground states is necessary to obtain a photocontrolled system rather than simply a photoinitiated system. The elucidation of the elementary steps of this process will aid the design of new catalytic systems and their real-world applications. PMID- 28985063 TI - Personalized Medicine for Crops? Opportunities for the Application of Molecular Recognition in Agriculture. AB - This perspective examines the detection of rhizosphere biomarkers, namely, root exudates and microbial metabolites, using molecular recognition elements, such as molecularly imprinted polymers, antibodies, and aptamers. Tracking these compounds in the rhizosphere could provide valuable insight into the status of the crop and soil in a highly localized way. The outlook and potential impact of the combination of molecular recognition and other innovations, such as nanotechnology and precision agriculture, and the comparison to advances in personalized medicine are considered. PMID- 28985065 TI - The Origin of Chalcogen-Bonding Interactions. AB - Favorable molecular interactions between group 16 elements have been implicated in catalysis, biological processes, and materials and medicinal chemistry. Such interactions have since become known as chalcogen bonds by analogy to hydrogen and halogen bonds. Although the prevalence and applications of chalcogen-bonding interactions continues to develop, debate still surrounds the energetic significance and physicochemical origins of this class of sigma-hole interaction. Here, synthetic molecular balances were used to perform a quantitative experimental investigation of chalcogen-bonding interactions. Over 160 experimental conformational free energies were measured in 13 different solvents to examine the energetics of O...S, O...Se, S...S, O...HC, and S...HC contacts and the associated substituent and solvent effects. The strongest chalcogen bonding interactions were found to be at least as strong as conventional H-bonds, but unlike H-bonds, surprisingly independent of the solvent. The independence of the conformational free energies on solvent polarity, polarizability, and H bonding characteristics showed that electrostatic, solvophobic, and van der Waals dispersion forces did not account for the observed experimental trends. Instead, a quantitative relationship between the experimental conformational free energies and computed molecular orbital energies was consistent with the chalcogen-bonding interactions being dominated by n -> sigma* orbital delocalization between a lone pair (n) of a (thio)amide donor and the antibonding sigma* orbital of an acceptor thiophene or selenophene. Interestingly, stabilization was manifested through the same acceptor molecular orbital irrespective of whether a direct chalcogen...chalcogen or chalcogen...H-C contact was made. Our results underline the importance of often-overlooked orbital delocalization effects in conformational control and molecular recognition phenomena. PMID- 28985066 TI - Emulsified and Liquid-Liquid Phase-Separated States of alpha-Pinene Secondary Organic Aerosol Determined Using Aerosol Optical Tweezers. AB - We demonstrate the first capture and analysis of secondary organic aerosol (SOA) on a droplet suspended in an aerosol optical tweezers (AOT). We examine three initial chemical systems of aqueous NaCl, aqueous glycerol, and squalane at ~75% relative humidity. For each system we added alpha-pinene SOA-generated directly in the AOT chamber-to the trapped droplet. The resulting morphology was always observed to be a core of the original droplet phase surrounded by a shell of the added SOA. We also observed a stable emulsion of SOA particles when added to an aqueous NaCl core phase, in addition to the shell of SOA. The persistence of the emulsified SOA particles suspended in the aqueous core suggests that this metastable state may persist for a significant fraction of the aerosol lifecycle for mixed SOA/aqueous particle systems. We conclude that the alpha-pinene SOA shell creates no major diffusion limitations for water, glycerol, and squalane core phases under humid conditions. These experimental results support the current prompt-partitioning framework used to describe organic aerosol in most atmospheric chemical transport models and highlight the prominence of core-shell morphologies for SOA on a range of core chemical phases. PMID- 28985064 TI - Synthesis of ent-[3]-Ladderanol: Development and Application of Intramolecular Chirality Transfer [2+2] Cycloadditions of Allenic Ketones and Alkenes. AB - An enantioselective synthesis of ent-[3]-ladderanol is presented. The ladderanes are an interesting class of molecules for their unique structure of fused cyclobutane rings as well as their perceived biological function of organism protection. The route hinges on the development and application of a chirality transfer [2+2] cycloaddition of an allenic ketone and alkene. Further stereocontrolled transformations allowed for completion of the synthesis. The scope of the chirality transfer [2+2] cycloaddition is also presented. PMID- 28985067 TI - Nickel Pincer Complexes with Frequent Aliphatic Alkoxo Ligands [(iPrPCP)Ni-OR] (R = Et, nBu, iPr, 2-hydroxyethyl). An Assessment of the Hydrolytic Stability of Nickel and Palladium Alkoxides. AB - A series of nickel pincer complexes with terminal alkoxo ligands [(iPrPCP)Ni-OR] (R = Et, nBu, iPr, CH2CH2OH; iPrPCP is the 2,6 bis(diisopropylphosphinomethyl)phenyl pincer ligand) was synthesized and fully characterized. Together with the previously reported methoxo analogues of Ni and Pd, these complexes constitute a unique series of isostructural late transition metal alkoxides. Spectroscopic and X-ray diffraction data provide direct indications of the strong polarization of their covalent Ni-OR bonds. One of the most salient features of this class of compounds is their facile hydrolysis with traces of moisture, leading to equilibrium mixtures with the corresponding hydroxides [(iPrPCP)M-OH] (M = Ni or Pd) and alcohols, ROH. To compare the hydrolytic stability of nickel and palladium alkoxides, we performed NMR titrations of both hydroxides with several alcohols and determined the corresponding equilibrium constants. In general, these constants are ca. 1 order of magnitude smaller for M = Ni than Pd, indicating that Ni alkoxide complexes are more readily hydrolyzed than their Pd counterparts. For alkoxide complexes containing heteroatom-free R groups, the tendency to hydrolyze decreases as the parent alcohol ROH becomes more acidic, that is, R = Me > Et > iPr. This intuitive trend is broken for 2-methoxyethanol, the most acidic alcohol investigated. The hydroxo/2-methoxyethanol exchange equilibrium constants are comparable to those of ethanol (M = Ni) or methanol (M = Pd), showing that the corresponding 2-methoxyethoxide complexes are more prone to hydrolysis than anticipated. These experimental observations were rationalized in the light of density functional theory calculations. PMID- 28985068 TI - Design of Wall-Destructive but Membrane-Compatible Solvents. AB - We report an extremely biocompatible solvent for plant cell walls based on a polar liquid zwitterion that dissolves cellulose, the most recalcitrant component of the plant cell walls. The polar liquid zwitterion does not affect the viability and activity of Escherichia coli, even at high concentrations. We demonstrate conversion of cell walls to ethanol via a starch-like process, namely successive dissolution, hydrolysis and fermentation in the same reaction pot. PMID- 28985069 TI - Shackling Effect Induced Property Differences in Metallo-Supramolecular Polymers. AB - We demonstrate here the synthesis of a novel class of metallo-supramolecular polymers with shackled structure, via the coordination of cyclic di(bis terpyridine-triphenyl ether ester) ligands with ruthenium(II) ions. The constraint from the ring topology via the shackling of ligands provides novel properties to these metallo-supramolecular polymers, including the formation of dendritic crystals, red-shift of absorption bands in the UV-vis spectra from interchain charge-transfer transitions, and a typical flash-type memory behavior. PMID- 28985070 TI - Cooperative Al-H Bond Activation in DIBAL-H: Catalytic Generation of an Alumenium Ion-Like Lewis Acid for Hydrodefluorinative Friedel-Crafts Alkylation. AB - The Ru-S bond in Ohki-Tatsumi complexes breaks oligomeric DIBAL-H structures into their more reactive monomer. That deaggregation is coupled to heterolytic Al-H bond activation at the Ru-S bond, formally splitting the Al-H linkage into hydride and an alumenium ion. The molecular structure of these Lewis pairs was established crystallographically, revealing an additional Ru-Al interaction next to the Ru-H and Al-S bonds. That bonding situation was further analyzed by quantum-chemical calculations and is best described as a three-center-two electron (3c2e) donor-acceptor sigma(Ru-H) -> Al interaction. Despite the extra stabilization of the aluminum center by the interaction with both the sulfur atom and the Ru-H bond, the hydroalane adducts are found to be stronger Lewis acids and electrophiles than the free ruthenium catalyst and DIBAL-H in its different aggregation states. Hence, the DIBAL-H molecule and its Al-H bond are activated by the Ru-S bond, but these hydroalane adducts are not to be mistaken as sulfur stabilized alumenium ions in a strict sense. The Ohki-Tatsumi complexes catalyze C(sp3)-F bond cleavage with DIBAL-H, and the catalytic setup is applied to hydrodefluorinative Friedel-Crafts alkylations. A broad range of CF3-substituted arenes is efficiently converted into unsymmetrical diarylmethanes with various arenes as nucleophiles. Computed fluoride-ion affinities (FIAs) of the hydroalane adducts as well as DIBAL-H in its aggregation states support this experimental finding. PMID- 28985072 TI - Crystallization-Induced Fouling during Boiling: Formation Mechanisms to Mitigation Approaches. AB - Boiling is significantly altered by the presence of dissolved salts. In particular, salts whose solubility decreases with temperature have the tendency to crystallize and adhere to the heat transfer surface and adversely affect the thermal performance. Scaling due to the precipitation of such salts poses serious operational and safety challenges in several practical applications, including heat exchangers, pipelines, and desalination. Here, we study the effect of dissolved salts on the dynamics of pool boiling and its impact on the heat transfer coefficient and critical heat flux (CHF). We find that even undersaturated conditions can lead to crystallization and scale buildup on the boiling surface and dramatically lower heat transfer performance. For example, the CHF for a salt solution that is 75% of the saturation concentration is found to be at least 2 times lower than that for deionized water. Using simultaneous high-speed optical and infrared imaging, we determine the interdependence between crystallization-induced scale formation and bubble evolution dynamics, including bubble nucleation, growth, and departure. We find that salt crystallizes in a "coffee-ring" pattern due to evaporation at the contact line of the bubble. On the basis of the role of the microlayer and triple contact line on scale formation, we propose manipulating surface wettability as a means to avoid scale formation and the associated decrease in the heat transfer coefficient. Surfaces with hybrid wettability are demonstrated as a means to mitigate the reduction in the heat transfer coefficient and CHF in the presence of dissolved salts. PMID- 28985071 TI - UiO-68-ol NMOF-Based Fluorescent Sensor for Selective Detection of HClO and Its Application in Bioimaging. AB - Fluorescent probes are powerful tools for the investigations of reactive oxygen species (ROS) in living organisms by visualization and imaging. As one of the most important of the natural reactive oxygen species (ROS), hypochlorous acid (HClO) plays a crucial role in various physiological and pathological processes. We report herein a new redox-switchable NMOF of UiO-68-ol via a direct ligand modification approach. The obtained UiO-68-ol NPs, which contains organic-based molecular redox switches, exhibit excellent photophysical properties for biological application and can be highly sensitive and selective fluorescent probes to detect HClO species in living cells. PMID- 28985073 TI - Excited-State Dynamics of Isocytosine: A Hybrid Case of Canonical Nucleobase Photodynamics. AB - We present resonant two-photon ionization (R2PI) spectra of isocytosine (isoC) and pump-probe results on two of its tautomers. IsoC is one of a handful of alternative bases that have been proposed in scenarios of prebiotic chemistry. It is structurally similar to both cytosine (C) and guanine (G). We compare the excited-state dynamics with the Watson-Crick (WC) C and G tautomeric forms. These results suggest that the excited-state dynamics of WC form of G may primarily depend on the heterocyclic substructure of the pyrimidine moiety, which is chemically identical to isoC. For WC isoC we find a single excited-state decay with a rate of ~1010 s-1, while the enol form has multiple decay rates, the fastest of which is 7 times slower than for WC isoC. The excited-state dynamics of isoC exhibits striking similarities with that of G, more so than with the photodynamics of C. PMID- 28985075 TI - Stochastic and Quasi-Stochastic Hamiltonians for Long-Time Nonadiabatic Molecular Dynamics. AB - In the condensed-matter environments, the vibronic Hamiltonian that describes nonadiabatic dynamics often appears as an erratic entity, and one may assume it can be generated stochastically. This property is utilized to formulate novel stochastic and quasi-stochastic vibronic Hamiltonian methodologies, which open a new route to long-time excited state dynamics in atomistic solid-state systems at negligible computational cost. Using a model mimicking a typical solid-state material in noisy environment, general conclusions regarding the simulation of nonadiabatic dynamics are obtained: (1) including bath is critical to complete excited state relaxation; (2) a totally stochastic modulation of energies and couplings has a net effect of no bath and inhibits relaxation; (3) including a single or several dominant electron-phonon modes may be insufficient to complete the excited state relaxation; (4) only the multiple modes, even those that have negligible weights, can represent both the deterministic modulation of system's Hamiltonian and stochastic effects of bath. PMID- 28985074 TI - Improved Method for Determining Absolute Phosphorylation Stoichiometry Using Bayesian Statistics and Isobaric Labeling. AB - Phosphorylation stoichiometry, or occupancy, is one element of phosphoproteomics that can add useful biological context (Gerber et al. Proc. Natl. Acad. Sci. U. S. A. 2003, 100, 6940-5). We previously developed a method to assess phosphorylation stoichiometry on a proteome-wide scale (Wu et al. Nat. Methods 2011, 8, 677-83). The stoichiometry calculation relies on identifying and measuring the levels of each nonphosphorylated counterpart peptide with and without phosphatase treatment. The method, however, is problematic in that low stoichiometry phosphopeptides can return negative stoichiometry values if measurement error is larger than the percent stoichiometry. Here, we have improved the stoichiometry method through the use of isobaric labeling with 10 plex TMT reagents. In this way, five phosphatase treated and five untreated samples are compared simultaneously so that each stoichiometry is represented by five ratio measurements with no missing values. We applied the method to determine basal stoichiometries of HCT116 cells growing in culture. With this method, we analyzed five biological replicates simultaneously with no need for phosphopeptide enrichment. Additionally, we developed a Bayesian model to estimate phosphorylation stoichiometry as a parameter confined to an interval between 0 and 1 implemented as an R/Stan script. Consequently, both point and interval estimates are consistent with the plausible range of values for stoichiometry. Finally, we report absolute stoichiometry measurements with credible intervals for 6772 phosphopeptides containing at least a single phosphorylation site. PMID- 28985076 TI - Dodecylmaltoside Modulates Bicellular Tight Junction Contacts To Promote Enhanced Permeability. AB - Intestinal permeation enhancers are a crucial component of many oral formulations, without which many drugs would show an insufficient absorption in the gut. The present study sought to provide a better understanding of the molecular interaction of such absorption enhancers with the intestine, by investigating the effect of the surfactant-like permeation enhancer dodecylmaltoside (DDM) on Caco-2 cells. The extent to which the action of DDM is apportioned between the para- and transcellular routes was addressed by examining the transport of relevant marker compounds ([3H]-mannitol and [3H]-propranolol, respectively). In the case of [3H]-mannitol, a robust permeation enhancement was achieved with 0.5 mM DDM (~6-fold), whereas little effect was seen on the permeation of [3H]-propranolol. Concomitantly measured TEER values revealed a rapid onset of action of DDM with a swift recovery and complete restitution (>90%) within 4 h after washout. To localize the site(s) of action of DDM at the absorptive surface of Caco-2 cells, sulfo-NHS-SS-biotin, a membrane-impermeable compound, was applied apically. In the presence of 0.5 mM DDM, translocated biotin was found to be accumulated toward bicellular contacts, whereas no biotin permeation was observed in untreated control cells. Western blot analysis of DDM treated and untreated Caco-2 cells revealed an interaction of DDM with specific tight junction associated proteins, resulting in a reduction of claudin-3 and -4 and also occludin, as well as a depletion of claudin-2 from lipid rafts. Collectively, the results presented provide a more in depth understanding of the molecular mechanism(s) underlying the permeation-enhancing actions of DDM. PMID- 28985077 TI - Direct Prediction of Calcite Surface Wettability with First-Principles Quantum Simulation. AB - Prediction of intrinsic surface wettability from first-principles offers great opportunities in probing new physics of natural phenomena and enhancing energy production or transport efficiency. We propose a general quantum mechanical approach to predict the macroscopic wettability of any solid crystal surfaces for different liquids directly through atomic-level density functional simulation. As a benchmark, the wetting characteristics of calcite crystal (10.4) under different types of fluids (water, hexane, and mercury), including either contact angle or spreading coefficient, are predicted and further validated with experimental measurements. A unique feature of our approach lies in its capability of capturing the interactions among various polar fluid molecules and solid surface ions, particularly their charge density difference distributions. Moreover, this approach provides insightful and quantitative predictions of complicated surface wettability alteration problems and wetting behaviors of liquid/liquid/solid triphase systems. PMID- 28985078 TI - Kinetics of Supersaturated Solution with Restricted Size of Precipitates in the Presence of Dimer Adsorption/Emission and Monomer-Monomer Agglomeration. AB - Kinetics of supersaturated solutions with restricted size of precipitating particles is considered using the microscopic theory which includes monomer monomer agglomeration (MMA) and dimer adsorption/emission (DAE). It is shown that the system passes, during its evolution from initial to final state, through four consecutive stages. In stage I and stage III, the scaled size distribution of particles changes quickly with increasing time while in stage II and stage IV it is almost independent of time. It is argued that during stage II the system, at any rates of MMA and DAE, is in a regime similar to the asymptotic regime provided by the classical Lifshitz-Slyouzov-Wagner (LSW) theory where no restrictions on the size of the particles are imposed and MMA and DAE are not considered. Extrapolating the time dependence of mean radius R of particles, obtained in range II, to large times provides the power law R ~ t1/nu where nu depends on the rates of MMA and DAE and changes from nu = 2 when MMA and DAE are absent and nu = 2.3 for comparatively large rates of MMA and DAE. This complements the result of the classical LSW approach where change of nu was attributed to the relationship between the rate of particles' diffusion and rate of adsorption of monomers on the surface of larger particles. During stage IV (large times), the system approaches exponentially the asymptotic state which is different from that for classical theory. The time behavior of the concentrations of the particles of largest size and of mean radius are examined for both asymptotic regimes. PMID- 28985079 TI - Dynamics and Novel Mechanisms of SN2 Reactions on ab Initio Analytical Potential Energy Surfaces. AB - We describe a novel theoretical approach to the bimolecular nucleophilic substitution (SN2) reactions that is based on analytical potential energy surfaces (PESs) obtained by fitting a few tens of thousands high-level ab initio energy points. These PESs allow computing millions of quasi-classical trajectories thereby providing unprecedented statistical accuracy for SN2 reactions, as well as performing high-dimensional quantum dynamics computations. We developed full-dimensional ab initio PESs for the F- + CH3Y [Y = F, Cl, I] systems, which describe the direct and indirect, complex-forming Walden inversion, the frontside attack, and the new double-inversion pathways as well as the proton-transfer channels. Reaction dynamics simulations on the new PESs revealed (a) a novel double-inversion SN2 mechanism, (b) frontside complex formation, PMID- 28985080 TI - Wettability of Reentrant Surfaces: A Global Energy Approach. AB - In this work, we consider two possible wetting states for a droplet when placed on a substrate: the Fakir configuration of a Cassie-Baxter (CB) state with a droplet residing on top of roughness grooves and the one characterized by the homogeneous wetting of the surface, referred as the Wenzel (W) state. We extend a theoretical model based on the global interfacial energies for both states CB and W to study the wetting behavior of simple and double reentrant surfaces. Due to the minimization of the energies associated with each wetting state, we predict the thermodynamic wetting state of the droplet for a given surface texture and obtain its contact angle thetaC. We first use this model to find the geometries for pillared, simple and double reentrant surfaces that most enhances thetaC and conclude that the repellent behavior of these surfaces is governed by the relation between the height and width of the reentrances. We compare our results with recent experiments and discuss the limitations of this thermodynamic approach. To address one of these limitations, we implement Monte Carlo simulations of the cellular Potts Model in three dimensions, which allow us to investigate the dependency of the wetting state on the initial state of the droplet. We find that when the droplet is initialized in a CB state, it gets trapped in a local minimum and stays in the repellent behavior irrespective of the theoretical prediction. When the initial state is W, simulations show a good agreement with theory for pillared surfaces for all geometries, but for reentrant surfaces the agreement only happens in few cases: for most simulated geometries the contact angle reached by the droplet in simulations is higher than thetaC predicted by the model. Moreover, we find that the contact angle of the simulated droplet is higher when placed on the reentrant surfaces than for a pillared surfaces with the same height, width and pillar distance. PMID- 28985081 TI - Multiphotochromism in an Asymmetric Ruthenium Complex with Two Different Dithienylethenes. AB - An asymmetric bis(dithienylethene-acetylide) ruthenium(II) complex trans Ru(dppe)2(L1o)(L2o) (1oo) incorporating two different dithienylethene-acetylides (L1o and L2o) was designed to modulate multistate photochromism in view of the well separated ring-closing absorption bands between L1o and L2o. Upon irradiation with appropriate wavelengths of light, complex 1 undergoes stepwise photocyclization and selective photocycloreversion to afford four states (1oo, 1co, 1oc, and 1cc). As a contrast, symmetric complexes trans-Ru(dppe)2(L1o)2 (2oo) and trans-Ru(dppe)2(L2o)2 (3oo) with two identical dithienylethene acetylides were synthesized, and the corresponding photochromic behavior was investigated. The photochromic properties of the oxidized species (1oo+/1co+/1oc+/1cc+, 2oo+/2co+/2cc+, and 3oo+/3co+/3cc+) were also investigated. The ring-closing absorption bands of one-electron oxidized species 1oo+, 2oo+, and 3oo+ show obvious blue shifts relative to those of 1oo, 2oo, and 3oo, respectively. The ring-closing absorption bands in both neutral and oxidized species grow progressively following oo -> oc/co -> cc and oo+ -> oc+/co+ -> cc+. As revealed by spectroscopic, electrochemical, and computational studies, complex 1 displays eight switchable states through stepwise photocyclization, selective cycloreversion, and a reversible redox process. PMID- 28985082 TI - Transformable Sulfoximine Assisted One-Pot Double Annulation of Vinylic C-H Bonds with Unactivated Alkynes. AB - The methylphenyl sulfoximine (MPS) directing group (DG) successfully promotes the one-pot double annulation of acrylic acids with alkynes under Ru catalysis, which is unprecedented. Diverse arrays of pyrido-fused-isoquinolinone skeletons are fabricated from acrylamides, creating two C-C and two C-N bonds in a single operation. The unsymmetrical annulation with two distinct alkynes is presented. The recovery of methylphenyl sulfoxide, a precursor of MPS, validates the synthetic adaptability of transformable-DG (TfDG) in C-H activation. PMID- 28985083 TI - Single-Molecule Photocurrent at a Metal-Molecule-Semiconductor Junction. AB - We demonstrate here a new concept for a metal-molecule-semiconductor nanodevice employing Au and GaAs contacts that acts as a photodiode. Current-voltage traces for such junctions are recorded using a STM, and the "blinking" or "I(t)" method is used to record electrical behavior at the single-molecule level in the dark and under illumination, with both low and highly doped GaAs samples and with two different types of molecular bridge: nonconjugated pentanedithiol and the more conjugated 1,4-phenylene(dimethanethiol). Junctions with highly doped GaAs show poor rectification in the dark and a low photocurrent, while junctions with low doped GaAs show particularly high rectification ratios in the dark (>103 for a 1.5 V bias potential) and a high photocurrent in reverse bias. In low doped GaAs, the greater thickness of the depletion layer not only reduces the reverse bias leakage current, but also increases the volume that contributes to the photocurrent, an effect amplified by the point contact geometry of the junction. Furthermore, since photogenerated holes tunnel to the metal electrode assisted by the HOMO of the molecular bridge, the choice of the latter has a strong influence on both the steady state and transient metal-molecule-semiconductor photodiode response. The control of junction current via photogenerated charge carriers adds new functionality to single-molecule nanodevices. PMID- 28985084 TI - Controlling Plasma Stability of Hydroxamic Acids: A MedChem Toolbox. AB - Hydroxamic acids are outstanding zinc chelating groups that can be used to design potent and selective metalloenzyme inhibitors in various therapeutic areas. Some hydroxamic acids display a high plasma clearance resulting in poor in vivo activity, though they may be very potent compounds in vitro. We designed a 57 member library of hydroxamic acids to explore the structure-plasma stability relationships in these series and to identify which enzyme(s) and which pharmacophores are critical for plasma stability. Arylesterases and carboxylesterases were identified as the main metabolic enzymes for hydroxamic acids. Finally, we suggest structural features to be introduced or removed to improve stability. This work thus provides the first medicinal chemistry toolbox (experimental procedures and structural guidance) to assess and control the plasma stability of hydroxamic acids and realize their full potential as in vivo pharmacological probes and therapeutic agents. This study is particularly relevant to preclinical development as it allows obtaining compounds equally stable in human and rodent models. PMID- 28985085 TI - Effect of Architecture on Micelle Formation and Liquid-Crystalline Ordering in Solutions of Block Copolymers Comprising Flexible and Rigid Blocks: Rod-Coil vs Y Shaped vs Comblike Copolymers. AB - Micelle formation of amphiphilic block copolymers of various architectures comprising both flexible and rodlike blocks were studied in a selective solvent via dissipative particle dynamics (DPD) simulations. Peculiarities of self assembly of Y-shaped (insoluble rigid block and two flexible soluble arms) and comblike (soluble flexible backbone with insoluble rigid side chains) copolymers are compared with those of equivalent rod-coil diblock copolymers. We have shown that aggregation of the rigid blocks into the dense core of the micelles is accompanied by their nematic ordering. However, the orientation order parameter and aggregation number of the micelles are strongly dependent on macromolecular architecture. Relatively small micelles of pretty high nematic order parameter, S2 ~ 0.5-0.8, are the features of the Y-shaped and rod-coil copolymer micelles. They are characterized by different responses to the solvent quality worsening. The aggregation number of the rod-coil diblock copolymer micelles increases and that of the Y-shaped copolymer micelles decreases at the solvent quality worsening. However, the order parameter grows in both cases, achieving a maximum value for the Y-shaped copolymer micelles. Herewith, the core elongates. On the contrary, comblike copolymers self-assemble into bigger spherical micelles whose core possesses a lower nematic order of the rods, S2 ~ 0.3-0.4. The aggregation number is shown to depend on the length of the combs (on the number of repeating elements in the architecture). Possible physical reasons for such behavior of the systems are discussed. PMID- 28985086 TI - Gingival melanin depigmentation by Er:YAG laser: A literature review. AB - Laser ablation is recently suggested as a most effective and reliable technique for depigmentation of melanin hyperpigmented gingiva. To date, different lasers have been used for gingival depigmentation (CO2, diode, Nd:YAG, Er:YAG and Er,Cr:YSGG lasers). The use of Er:YAG laser for depigmentation of melanin hyperpigmented gingiva has gained increasing importance in recent years. The purpose of this study was to report removal of gingival melanin pigmentation using an Er:YAG laser in a literature review. The main outcomes, such as improvement of signs (clinical parameters of bleeding, erythema, swelling and wound healing), symptoms (pain) and melanin recurrence/repigmentation were measured. The literature demonstrated that depigmentation of gingival melanin pigmentation can be performed safely and effectively by Er:YAG laser resulting in healing and an esthetically significant improvement of gingival discoloration. Thus, Er:YAG laser seems to be safe and useful in melanin depigmentation procedure. However, the main issue in giving the final conclusion of the optimal Er:YAG laser use in melanin depigmentation is that, to date, studies are offering completely discrepant Er:YAG laser procedure protocols (complex settings of laser parameters), and different criteria for the assessment of depigmentation and repigmentation (recurrence), thus hampering the comparison of the results. Therefore, further studies are necessary to give an optimal recommendation on the use of Er:YAG laser in gingival melanin hyperpigmentation. PMID- 28985087 TI - Letter to the editor: Association of tear stability and corneal surface temperature. PMID- 28985088 TI - Modeling influences of dopamine on synchronization behavior of striatum. AB - A network model of striatum that comprises medium spiny neurons (MSNs) and fast spiking interneurons (FSIs) is constructed following the work of Humphries et al. (2009). The dynamic behavior of striatum microcircuit is investigated using a dopamine-modulated modified Izhikevich neuron model. The influences of dopamine on the synchronization behavior of the striatal microcircuit and the dependence on receptor type are investigated with and without time delay. To investigate the role of two types of dopamine receptors, D1 and D2, on the overall activity of the striatum microcircuit, the activities of two groups are considered as disconnected and connected. When the connection exists between D1 and D2 sub networks with zero dopamine and time delay, neuronal activity decreases because of an inhibitory effect of the connected neurons of the other sub-network. In the presence of dopamine, an increase in the activity of D1 type MSNs and quiescent behavior of D2 type MSNs are observed when the time delay is zero. However, the diversity in synchronization of D1 and D2 type MSNs is observed for different synaptic time delays and synaptic strengths in the case that dopamine is present. PMID- 28985089 TI - Examining participant perceptions of an interprofessional simulation-based trauma team training for medical and nursing students. AB - High quality care relies on interprofessional teamwork. We developed a short simulation-based course for final year medical, nursing and nursing anaesthesia students, using scenarios from emergency medicine. The aim of this paper is to describe the adaptation of an interprofessional simulation course in an undergraduate setting and to report participants' experiences with the course and students' learning outcomes. We evaluated the course collecting responses from students through questionnaires with both closed-ended and open-ended questions, supplemented by the facilitators' assessment of students' performance. Our data is based on responses from 310 students and 16 facilitators who contributed through three evaluation phases. In the analysis, we found that students reported emotional activation and learning outcomes within the domains self-insight and stress management, understanding of the leadership role, insight into teamwork, and skills in team communication. In subsequent questionnaire studies students reported having gained insights about communication, teamwork and leadership, and they believed they would be better leaders of teams and/or team members after having completed the course. Facilitators' observations suggested a progress in students' non-technical skills during the course. The facilitators observed that nursing anaesthesia students seemed to be more comfortable in finding their role in the team than the two other groups. In conclusion, we found that an interprofessional simulation-based emergency team training course with a focus on leadership, communication and teamwork, was feasible to run on a regular basis for large groups of students. The course improved the students' team skills and received a favourable evaluation from both students and faculty. PMID- 28985091 TI - Letters to the Editor. PMID- 28985090 TI - Policies to mitigate nonmedical use of prescription medications: how should emerging evidence of gabapentin misuse be addressed? AB - INTRODUCTION: Over the past decade, increased prescription supply has facilitated an epidemic of nonmedical use of controlled substances, including predominantly opioids, as well as benzodiazepines, z-hypnotics, and stimulants. Areas covered: More recently, misuse of noncontrolled prescriptions, such as gabapentin, has been detected. Gabapentin misuse has been associated with drug-related harm and increased healthcare service utilization in a few studies, including a recent large-sample analysis of commercially insured enrollees in the United States (U.S.) Responding to this emerging base of evidence, a small number of U.S. states have acted to prevent or detect gabapentin misuse by requiring the inclusion of gabapentin utilization in reporting to local Prescription Drug Monitoring Programs (PDMPs) and/or imposing other restrictions on gabapentin prescribing (e.g., classification as a controlled substance, quantity limits). These efforts may result in unintentional harm by (1) encouraging 'doctor shopping' across state lines to seek lenient regulatory policies and (2) placing the burden for mitigating misuse on individual practitioners. Expert opinion: We call for a unified national approach, comprising federal regulation and enhanced PDMP reporting to address gabapentin misuse, while laying the groundwork for management of new medications of abuse that the healthcare industry may encounter in the future. PMID- 28985092 TI - Resveratrol Ameliorates Retinal Ischemia/Reperfusion Injury in C57BL/6J Mice via Downregulation of Caspase-3. AB - PURPOSE: Ischemia/reperfusion (I/R) injury induces apoptosis in retinal ganglion cells (RGCs). Resveratrol (Res) is a potent natural antioxidant with beneficial effects in many ocular diseases, such as age-related macular degeneration, diabetic retinopathy, and glaucoma. Because caspase-3 expression is highly correlated with activation of the apoptotic pathway, the present study aimed to determine whether Res regulates the expression of caspase-3 using an I/R retinal injury mouse model. METHODS: Male C57BL/6J mice were injected with Res for 2 consecutive days before I/R retinal injury. I/R retinal injury was induced by increasing the intraocular pressure for 1 h. Res was then injected for 3 consecutive days. Changes in retinal morphology were monitored for 3 days after injury by histochemistry using hematoxylin and eosin staining. mRNAs and proteins were extracted 2 days after injury. The expression levels of caspase-8 and caspase-3 mRNA and protein were determined using reverse-transcriptase polymerase chain reaction (RT-PCR) and western blot analyses. RESULTS: I/R injury induced declines in retinal thickness and number of RGCs during 5 days after injury. Caspase-8 and caspase-3 mRNA and protein activation increased. Res treatment reduced the significant loss of retinal morphology and downregulated the expression of mRNA and activation of caspase-8 and caspase-3 protein. CONCLUSIONS: The observed changes in retinal morphology suggest that I/R injury promotes retinal degeneration. Increased expression of caspase-8 and caspase-3 mRNA indicates apoptosis activation. Res, however, suppresses apoptosis via downregulation of caspase-8 and caspase-3 expression. PMID- 28985093 TI - Effects of Offense, Defense, and Ball Possession on Mobility Performance in Wheelchair Basketball. AB - The aim of this study was to determine to what extent mobility performance is influenced by offensive or defensive situations and ball possession and to what extent these actions are different for the field positions. From video analysis, the relative duration of the various wheelchair movements during team offense/defense and individual ball possession was compared in 56 elite wheelchair basketball players. A two-way analysis of variance indicated that during offense, the guards and forwards performed longer driving forward than during defense. Overall, centers stood still longer during offense than during defense. Without ball, centers performed driving forward longer than with ball possession. It is concluded that offense, defense, and ball possession influenced mobility performance for the different field positions. These differences can be used to design specific training protocols. Furthermore, field positions require potentially different specific wheelchair configurations to improve performance. PMID- 28985094 TI - Patellar Instability Management: A Survey of the International Patellofemoral Study Group. AB - BACKGROUND:: Although patellofemoral instability is among the most prevalent knee disorders, the management of patients with this condition is complex and remains variable, given the lack of long-term, high-level clinical outcome studies to compare various operative and nonoperative modalities. PURPOSE:: To discover a consensus within treatment controversies in patellofemoral instability among experienced knee surgeons with a specific interest in the patellofemoral joint. STUDY DESIGN:: Expert opinion; Level of evidence, 5. METHODS:: A 3-step modified Delphi technique was used to establish a consensus. A 34-question, case-based online survey regarding patellofemoral instability was distributed to all active members of the International Patellofemoral Study Group. Consensus statements were generated if at least 66% of the respondents agreed and then redistributed to the same panel. Modifications to the consensus statements were made based on the iterative feedback process until no discordance was encountered in the third stage. RESULTS:: Eight consensus statements were achieved. Nonoperative management is the current standard of care for a first-time dislocation in the absence of an osteochondral fragment or loose body requiring excision (100% agreement). In patients with a first-time dislocation with an operative osteochondral fracture requiring excision or repair, patellar instability should be addressed concurrently (89% agreement). Recurrent instability should be treated surgically, with most surgeons favoring medial reconstruction (77%-86% agreement). While there is general agreement that bony procedures should be performed to correct underlying bony deformities, there is no consensus regarding the most appropriate type of procedure performed. Lateral release should not be performed in isolation for the treatment of patellar instability (89% agreement). CONCLUSION:: Despite the consensus generated in this study, our current understanding remains limited by a lack of high-level evidence as well as the numerous complex variables influencing treatment decision making. High-quality, multicenter randomized controlled trials, particularly those directly comparing specific surgical treatment methods while controlling for underlying risk factors, are needed to address these areas of uncertainty. PMID- 28985095 TI - A Propensity-Matched Analysis of Outcomes of Patients with Clinical Stage I Non Small Cell Lung Cancer Treated surgically or with stereotactic radiotherapy: A Meta-Analysis. AB - OBJECTIVE: The aim of this study was to compare the efficacy between SBRT and surgery based on the Propensity-Matched Analysis. METHODS: Publications on comparison SBRT and Surgery for early stage non- small cell lung cancer (NSCLC) from 2011 to 2017 were collected. Propensity score matching was used to achieve comparable treatment hazard ratios of the overall survival (OS), local control survival (LC), regional control survival (RC), loco-regional control survival (LRC), distant control survival (DC), disease-free survival (DFS), and progression-free survival (PFS) between SBRT and Surgery. The major outcomes measures were hazard ratios (HRs). Meta-analysis Revman 5.3 software was used to analyze the combined Pooled HRs using fixed- or random-effects models according to the heterogeneity. RESULT: Eleven studies met our inclusion criteria. The LC, L-R C, DC, DFS and PFS rates of patients with early-stage lung cancer who were treated with SBRT are equal to surgical results. While, patients with surgery achieved superior OS compared with SBRT. CONCLUSION: In this study we carried out a meta-analysis, which controls the acceptable level of the efficacy in the propensity score to match patients. The surgery had obvious OS advantages in this meta-analysis. However, these conclusions would be proven by further studies incorporating comorbidity data, and outcomes from randomized control study. The final decision for the optimal treatment of a patient with early-stage NSCLC can be substantiated by a personalized treatment model. PMID- 28985097 TI - Statement of Retraction. PMID- 28985096 TI - Parents' Perspectives of Physical Activity in Their Adult Children With Autism Spectrum Disorder: A Social-Ecological Approach. AB - The purpose of this study was to investigate parent perceptions of the physical activity (PA) engagement of their adult children with autism spectrum disorders. The theoretical framework used in this study was social ecology. Participants were nine parents from families with one adult child with autism spectrum disorder whose ages ranged from 18 to 42. Using phenomenological interviews, which explored parents' life experience and meaning making, four themes were generated: supports and advocacy for PA, engaging in PA independently, benefits of PA, and barriers to or reasons for disengaging in particular activities. Parents' interview comments showed that intrapersonal factors, interpersonal relationships, and community factors were essential for keeping the individuals with autism spectrum disorder engaged in PA. Families and practitioners can take advantage of that by seeking PA opportunities in community settings or with other individuals. PMID- 28985098 TI - Retinal Nerve Fiber Layer Thickness in Human T-cell Lymphotropic Virus Type 1 Patients. AB - PURPOSE: To determine whether there is an optic neuropathy (ON) in patients with human T-cell lymphotropic virus type 1 (HTLV-1) infection. METHODS: We included HTLV-1 asymptomatic carriers (a.c.HTLV-1) and tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM) patients between January 1st, 2014 and March 31st, 2015. All patients had complete eye examination. The visual acuity (VA) and retinal nerve fiber layer (RNFL) thickness were measured and compared to age- and sex-matched control groups including patients seen in our refraction clinic with no previous medical or surgical history. RESULTS: Thirty-one a.c.HTLV-1 (group 1) and 29 TSP/HAM patients (group 2) were included. The average RNFL thickness was 99.9 +/- 14.3 um in group 1 and 87.8 +/- 19.2 um in group 2. The average RFNL thicknesses were lower in both groups, when compared to controls. The difference was significant in patients with TSP/HAM (87.8 +/- 19.2 um vs. 97 +/- 7.8 um; p = 0.003) who also had significantly decreased VA. CONCLUSIONS: We report here the first study about the RNFL thickness in patients with TSP/HAM. In these patients, there is decrease of the RNFL thickness with subtle but definite decrease of VA. This suggests that subclinical ON occurs in the natural history of the disease. The diagnosis of TSP/HAM must be evoked as a differential of primary progressive multiple sclerosis in a population at risk. Moreover, RNFL thinning with no evidence of glaucoma should raise suspicion for HTLV-1 infection and TSP/HAM in a population at risk. PMID- 28985099 TI - Physical Activity Among Adolescents With Long-Term Illnesses or Disabilities in 15 European Countries. AB - Physical activity (PA) is an important health-promoting behavior from which adolescents with long-term illnesses or disabilities (LTID) can benefit. It is important to monitor differences across countries in adherence with PA recommendations for health. The aim of this study was to compare PA levels among 15 European countries after disaggregating data by disability. Data from pupils (mean age = 13.6 years, SD = 1.64) participating in the 2013/2014 Health Behavior in School-aged Children study were analyzed to compare adolescents without LTID, with LTID, and with LTID that affects their participation (affected LTID). Logistic regression models adjusted for age and family affluence, stratified by gender and country group with PA recommendations for health as the outcome variable. With the data pooled, 15% (n = 9,372) of adolescents reported having LTID and 4% (n = 2,566) having affected LTID. Overall, fewer boys with LTID met PA recommendations for health than boys without LTID, although it was not statistically significant either at the national levels or for girls. PMID- 28985100 TI - Aerobic Exercise During Encoding Impairs Hippocampus-Dependent Memory. AB - We investigated how aerobic exercise during encoding affects hippocampus dependent memory through a source memory task that assessed hippocampus independent familiarity and hippocampus-dependent recollection processes. Using a within-participants design, young adult participants performed a memory-encoding task while performing a cycling exercise or being seated. The subsequent retrieval phase was conducted while sitting on a chair. We assessed behavioral and event-related brain potential measures of familiarity and recollection processes during the retrieval phase. Results indicated that source accuracy was lower for encoding with exercise than for encoding in the resting condition. Event-related brain potential measures indicated that the parietal old/new effect, which has been linked to recollection processing, was observed in the exercise condition, whereas it was absent in the rest condition, which is indicative of exercise-induced hippocampal activation. These findings suggest that aerobic exercise during encoding impairs hippocampus-dependent memory, which may be attributed to inefficient source encoding during aerobic exercise. PMID- 28985101 TI - The Man in the Vest. PMID- 28985102 TI - Klatskin Tumor. PMID- 28985103 TI - Low Bone Mineral Density in Male Athletes Is Associated With Bone Stress Injuries at Anatomic Sites With Greater Trabecular Composition. AB - BACKGROUND: While sports participation is often associated with health benefits, a subset of athletes may develop impaired bone health. Bone stress injuries (BSIs) are a common overuse injury in athletes; site of injury has been shown to relate to underlying bone health in female athletes. Hypothesis/Purpose: This case series characterizes the association of type of sports participation and anatomic site of BSIs with low bone mineral density (BMD), defined as BMD Z-score <-1.0. Similar to female athletes, it was hypothesized that male athletes who participate in running and sustain BSIs in sites of higher trabecular bone content would be more likely to have low BMD. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Chart review identified 28 male athletes aged 14 to 36 years with history of >=1 lower-extremity BSI who were referred for evaluation of overall bone health, including assessment of lumbar spine, hip, and/or total body less head BMD per dual-energy x-ray absorptiometry. BMD Z-scores were determined via age, sex, and ethnicity normative values. Prior BSIs were classified by anatomic site of injury into trabecular-rich locations (pelvis, femoral neck, and calcaneus) and cortical-rich locations (tibia, fibula, femur, metatarsal and tarsal navicular). Sport type and laboratory values were also assessed in relationship to BMD. The association of low BMD to anatomic site of BSI and sport were evaluated with P value <.05 as threshold of significance. RESULTS: Of 28 athletes, 12 (43%) met criteria for low BMD. Athletes with a history of trabecular-rich BSIs had a 4.6-fold increased risk for low BMD as compared with those with only cortical-rich BSIs (9 of 11 vs 3 of 17, P = .002). Within sport type, runners had a 6.1-fold increased risk for low BMD versus nonrunners (11 of 18 vs 1 of 10, P = .016). Laboratory values, including 25-hydroxy vitamin D, were not associated with BMD or BSI location. CONCLUSION: Low BMD was identified in 43% of male athletes in this series. Athletes participating in sports of running and with a history of trabecular-rich BSI were at increased risk for low BMD. PMID- 28985104 TI - Sport Participation for Elite Athletes With Physical Disabilities: Motivations, Barriers, and Facilitators. AB - There are many reasons why individuals are motivated to participate in sports. Less attention, however, is given for studying motivation and athlete development in adapted sport. The purpose of this study was to identify the motivations, facilitators, and barriers to sports participation of elite athletes with a physical disability. Participants (N = 23, 17 males, six females, mean age: 24.3 years) were recruited through online listservs, e-mails, and snowball sampling. A semistructured interview guide was employed. Analysis was conducted and grounded in self-determination theory and literature surrounding barriers and facilitators of sports participation. Through coding by multiple researchers, six themes emerged. Themes indicated that athletes attributed participation to constructs of self-determination theory as well as overcoming specific barriers such as cost, time constraints, and lack of opportunity. Among facilitators to their athletic development, there were empowerment and advocacy, increased health, college scholarships, and achieving performance-related goals. PMID- 28985105 TI - Class II malocclusion treatment effects with Jones Jig and Distal Jet followed by fixed appliances. AB - OBJECTIVES: To compare the skeletal, dentoalveolar, and soft tissue changes in Class II malocclusion patients treated with Jones Jig and Distal Jet distalizers followed by fixed appliances. MATERIALS AND METHODS: The experimental groups comprised 45 Class II malocclusion subjects divided into two groups. Group 1 consisted of 25 patients treated with the Jones Jig, and group 2 consisted of 20 patients treated with the Distal Jet. Group 3 comprised 19 untreated Class II subjects. Cephalograms were analyzed before and after orthodontic treatment. For intergroup comparisons, one-way analysis of variance and post hoc Tukey tests were performed. RESULTS: During treatment, the experimental groups exhibited significant increases in occlusal plane inclination and maxillary second molar mesial tipping. Additionally, the molar relationship improved and overjet decreased significantly in the experimental groups. The Jones Jig group showed greater mandibular incisor proclination and greater overbite reduction than the control group. No significant intergroup differences in nasolabial angle changes were found. CONCLUSIONS: Treatment protocols using the Jones Jig and Distal Jet followed by fixed appliances were effective in correcting Class II malocclusion by means of dentoalveolar changes without significant skeletal and soft tissue changes. The experimental groups showed occlusal plane clockwise rotation and greater mesial tipping of maxillary second molars when compared to the untreated group. PMID- 28985106 TI - A comparative study of the effect of the intrusion arch and straight wire mechanics on incisor root resorption: A randomized, controlled trial. AB - OBJECTIVE: To analyze and compare external apical root resorption (EARR) of maxillary incisors treated by intrusion arch or continuous archwire mechanics. MATERIALS AND METHODS: This cone-beam computed tomography (CBCT) study analyzed 28 deep bite patients in the permanent dentition who were randomly divided into two groups: Group 1, 12 patients with initial mean age of 15.1 +/- 1.6 years and mean overbite of 4.6 +/- 1.2 mm treated with the Connecticut intrusion arch (CIA) in the upper arch (Ortho Organizers, Carlsbad, Calif) for a mean period of 5.8 +/ 1.27 months. Group 2, 16 patients with initial mean age of 22.1 +/- 5.7 years and mean overbite of 4.1 +/- 1.1 mm treated with conventional leveling and alignment using continuous archwire mechanics for 6.1 +/- 0.81 months. The degree of EARR was detected in 112 maxillary incisors by using CBCT scans and a three dimensional program (Dolphin 11.7, Dolphin Imaging & Management Solutions, Chatsworth, Calif). The CBCT scans were obtained before (T1) and 6 months after initiation of treatment (T2). Differences between and within groups were assessed by nonpaired and paired t-tests, respectively, with a 5% significance level. RESULTS: Significant differences were found for both groups between T1 and T2 ( P < .05) indicating that EARR occurred in both groups. However, there were no significant differences when EARR was compared between group 1 (-0.76 mm) and group 2 (-0.59 mm). CONCLUSIONS: The Connecticut intrusion arch did not lead to greater EARR of maxillary incisors when compared with conventional orthodontic mechanics. PMID- 28985107 TI - A comparison of treatment effects of total arch distalization using modified C palatal plate vs buccal miniscrews. AB - OBJECTIVE: The purpose of this study was to compare the treatment effects of palatally vs buccally placed temporary anchorage devices. MATERIALS AND METHODS: Of 40 Class II division 1 malocclusion patients, 22 were treated with modified C palatal plate (MCPP) appliances (age 21.9 +/- 6.6 years), and 18 (age 24.2 +/- 6.8 years) were treated with buccally placed miniscrews between the maxillary first molar and second premolar. A total of 26 linear and angular measurements were analyzed on pre- and posttreatment lateral cephalograms. Multivariate analysis of variance was performed to evaluate the treatment effects within each group and to compare the effects between groups. RESULTS: Overall, the MCPP appliances showed 4.2 mm of distalization, 1.6 mm of intrusion of the first molar with 2 degrees tipping, and 0.8 mm extrusion of incisors. The miniscrew group resulted in 2.0 mm of distalization, 0.1 mm intrusion of the first molar with 7.2 degrees tipping, and 0.3 mm of incisor extrusion. Regarding soft tissue change, in the MCPP group, the upper lip was significantly retracted ( P < .001). CONCLUSIONS: Comparing the treatment effects between MCPP appliances and buccal miniscrews, the MCPP appliances showed greater distalization and intrusion with less distal tipping of the first molar and less extrusion of the incisor compared to the buccal miniscrews. PMID- 28985108 TI - Editorial. PMID- 28985110 TI - Uncorrected and corrected refractive error experiences of Nepalese adults: a qualitative study. AB - PURPOSE: The aim of this study was to explore the impact of corrected and uncorrected refractive error (URE) on Nepalese people's quality of life (QoL), and to compare the QoL status between refractive error subgroups. METHODS: Participants were recruited from Tilganga Institute of Ophthalmology and Dhulikhel Hospital, Nepal. Semi-structured in-depth interviews were conducted with 101 people with refractive error. Thematic analysis was used with matrices produced to compare the occurrence of themes and categories across participants. Themes were identified using an inductive approach. RESULTS: Seven major themes emerged that determined refractive error-specific QoL: activity limitation, inconvenience, health concerns, psycho-social impact, economic impact, general and ocular comfort symptoms, and visual symptoms. Activity limitation, economic impact, and symptoms were the most important themes for the participants with URE, whereas inconvenience associated with wearing glasses was the most important issue in glasses wearers. Similarly, possibilities of having side effects or complications were the major concerns for participants wearing contact lens. In general, refractive surgery addressed socio-emotional impact of wearing glasses or contact lens. However, the surgery participants had concerns such as possibility of having to wear glasses again due to relapse of refractive error. CONCLUSION: Impact of refractive error on people's QoL is multifaceted. Significance of the identified themes varies by refractive error subgroups. Refractive correction may not always address QoL impact of URE but often add unique QoL issues. This study findings also provide content for developing an item-bank for quantitatively measuring refractive error-specific QoL in developing country setting. PMID- 28985111 TI - A Chemical Reaction Network to Generate Random, Power-Law-Distributed Time Intervals. AB - In Levy walks (LWs), particles move with a fixed speed along straight line segments and turn in new directions after random time intervals that are distributed according to a power law. Such LWs are thought to be an advantageous foraging and search strategy for organisms. While complex nervous systems are certainly capable of producing such behavior, it is not clear at present how single-cell organisms can generate the long-term correlated control signals required for a LW. Here, we construct a biochemical reaction system that generates long-time correlated concentration fluctuations of a signaling substance, with a tunable fractional exponent of the autocorrelation function. The network is based on well-known modules, and its basic function is highly robust with respect to the parameter settings. PMID- 28985109 TI - Bioequivalence of a Liquid Formulation of Alpha1-Proteinase Inhibitor Compared with Prolastin(r)-C (Lyophilized Alpha1-PI) in Alpha1-Antitrypsin Deficiency. AB - This study evaluated the bioequivalence, safety, and immunogenicity of a new liquid formulation of human plasma-derived alpha1-proteinase inhibitor, Liquid Alpha1-PI, compared with the Lyophilized Alpha1-PI formulation (Prolastin(r)-C), for augmentation therapy in patients with alpha1-antitrypsin deficiency (AATD). In this double-blind, randomized, 20-week crossover study, 32 subjects with AATD were randomized to receive 8 weekly infusions of 60 mg/kg of Liquid Alpha1-PI or Lyophilized Alpha1-PI. Serial blood samples were drawn for 7 days after the last dose followed by 8 weeks of the alternative treatment. The primary endpoint was bioequivalence at steady state, as measured by area under the concentration versus time curve from 0 to 7 days (AUC0-7 days) postdose using an antigenic content assay. Bioequivalence was defined as 90% confidence interval (CI) for the ratio of the geometric least squares (LS) mean of AUC0-7 days for both products within the limits of 0.80 and 1.25. Safety and immunogenicity were assessed. Mean alpha1-PI concentration versus time curves for both formulations were superimposable. Mean AUC0-7 days was 20 320 versus 19 838 mg * h/dl for Liquid Alpha1-PI and Lyophilized Alpha1-PI, respectively. The LS mean ratio of AUC0-7 days (90% CI) for Liquid Alpha1-PI versus Lyophilized Alpha1-PI was 1.05 (1.03 1.08), indicating bioequivalence. Liquid Alpha1-PI was well tolerated and adverse events were consistent with Lyophilized Alpha1-PI. Immunogenicity to either product was not detected. In conclusion, Liquid Alpha1-PI is bioequivalent to Lyophilized Alpha1-PI, with a similar safety profile. The liquid formulation would eliminate the need for reconstitution and shorten preparation time for patients receiving augmentation therapy for AATD. PMID- 28985112 TI - Minimally Sufficient Conditions for the Evolution of Social Learning and the Emergence of Non-Genetic Evolutionary Systems. AB - Social learning, defined as the imitation of behaviors performed by others, is recognized as a distinctive characteristic in humans and several other animal species. Previous work has claimed that the evolutionary fixation of social learning requires decision-making cognitive abilities that result in transmission bias (e.g., discriminatory imitation) and/or guided variation (e.g., adaptive modification of behaviors through individual learning). Here, we present and analyze a simple agent-based model that demonstrates that the transition from instinctive actuators (i.e., non-learning agents whose behavior is hardcoded in their genes) to social learners (i.e., agents that imitate behaviors) can occur without invoking such decision-making abilities. The model shows that the social learning of a trait may evolve and fix in a population if there are many possible behavioral variants of the trait, if it is subject to strong selection pressure for survival (as distinct from reproduction), and if imitation errors occur at a higher rate than genetic mutation. These results demonstrate that the (sometimes implicit) assumption in prior work that decision-making abilities are required is incorrect, thus allowing a more parsimonious explanation for the evolution of social learning that applies to a wider range of organisms. Furthermore, we identify genotype-phenotype disengagement as a signal for the imminent fixation of social learners, and explain the way in which this disengagement leads to the emergence of a basic form of cultural evolution (i.e., a non-genetic evolutionary system). PMID- 28985113 TI - Droplets As Liquid Robots. AB - Liquid droplets are very simple objects present in our everyday life. They are extremely important for many natural phenomena as well as for a broad variety of industrial processes. The conventional research areas in which the droplets are studied include physical chemistry, fluid mechanics, chemical engineering, materials science, and micro- and nanotechnology. Typical studies include phenomena such as condensation and droplet formation, evaporation of droplets, or wetting of surfaces. The present article reviews the recent literature that employs droplets as animated soft matter. It is argued that droplets can be considered as liquid robots possessing some characteristics of living systems, and such properties can be applied to unconventional computing through maze solving or operation in logic gates. In particular, the lifelike properties and behavior of liquid robots, namely (i) movement, (ii) self-division, and (iii) group dynamics, will be discussed. PMID- 28985114 TI - The Evolution of Sex through the Baldwin Effect. AB - This article suggests that the fundamental haploid-diploid cycle of eukaryotic sex exploits a rudimentary form of the Baldwin effect. With this explanation for the basic cycle, the other associated phenomena can be explained as evolution tuning the amount and frequency of learning experienced by an organism. Using the well-known NK model of fitness landscapes, it is shown that varying landscape ruggedness varies the benefit of the haploid-diploid cycle, whether based upon endomitosis or syngamy. The utility of pre-meiotic doubling and recombination during the cycle are also shown to vary with landscape ruggedness. This view is suggested as underpinning, rather than contradicting, many existing explanations for sex. PMID- 28985115 TI - A New Home for a Vital Conversation: Introducing the ALife Societal Impact Section and Going Back to Bio-Inspiration for the Internet. PMID- 28985116 TI - RAIN: A Bio-Inspired Communication and Data Storage Infrastructure. AB - We summarize the results and perspectives from a companion article, where we presented and evaluated an alternative architecture for data storage in distributed networks. We name the bio-inspired architecture RAIN, and it offers file storage service that, in contrast with current centralized cloud storage, has privacy by design, is open source, is more secure, is scalable, is more sustainable, has community ownership, is inexpensive, and is potentially faster, more efficient, and more reliable. We propose that a RAIN-style architecture could form the backbone of the Internet of Things that likely will integrate multiple current and future infrastructures ranging from online services and cryptocurrency to parts of government administration. PMID- 28985117 TI - On the Relation between Chemical Oscillations and Self-Replication. AB - One proposed scenario for the emergence of biochemical oscillations is that they may have provided the basic mechanism behind cellular self-replication by growth and division. However, alternative scenarios not requiring any chemical oscillation have also been proposed. Each of the various protocell models proposed to support one or another scenario comes with its own set of specific assumptions, which makes it difficult to ascertain whether chemical oscillations are required or not for cellular self-replication. This article compares these two cases within a single whole-cell model framework. This model relies upon a membrane embedding a chemical reaction network (CRN) synthesizing all the cellular constituents, including the membrane, by feeding from an external nutrient. Assuming the osmolarity is kept constant, the system dynamics are governed by a set of nonlinear differential equations coupling the chemical concentrations and the surface-area-to-volume ratio. The resulting asymptotic trajectories are used to determine the cellular shape by minimizing the membrane bending energy (within an approximate predefined family of shapes). While the stationary case can be handled quite generally, the oscillatory one is investigated using a simple oscillating CRN example, which is used to identify features that are expected to hold for any network. It is found that cellular self-replication can be reached with or without chemical oscillations, and that a requirement common to both stationary and oscillatory cases is that a minimum spontaneous curvature of the membrane is required for the cell to divide once its area and volume are both doubled. The oscillatory case can result in a greater variety of cellular shape trajectories but raises additional constraints for cellular division and self-replication: (i) the ratio of doubling time to oscillation period should be an integer, and (ii) if the oscillation amplitude is sufficiently high, then the spontaneous curvature must be below a maximum value to avoid early division before the end of the cycle. Because of these additional stringent constraints, it is likely that early protocells did not rely upon chemical oscillations. Biochemical oscillations typical of modern evolved cells may have emerged later through evolution for other reasons (e.g., metabolic advantage) and must have required additional feedback mechanisms for such a self replicating system to be robust against even slight environmental variations (e.g., temperature fluctuations). PMID- 28985119 TI - FROM THE EDITOR - ABOUT THIS ISSUE ON YOUTHFUL OFFENDERS. PMID- 28985118 TI - THE CHALLENGE OF JUVENILE JUSTICE: ADVOCATING FOR TROUBLED CHILDREN IN TROUBLE. AB - Psychiatric nurses have long advocated for children with mental disorders, but few have gone behind bars to advocate for these youth. This paper offers suggestions for advocating on behalf of the most underserved of children?youthful offenders. Efforts in Maryland, as an example, portray conflicting convictions: to punish or to treat. These conflicting convictions permeate our juvenile laws, juvenile facilities, and treatment programs. A discussion of successful programming demonstrates the strengths of advocacy and the difference one person can make. Steps are outlined to assist nurses in the development of activist roles in advocating for these troubled youth. PMID- 28985120 TI - AN OVERVIEW OF FORENSIC PSYCHIATRIC CARE OF THE ADOLESCENT. AB - The field of forensic psychiatric nursing is a relatively recent addition to the specialty of psychiatric nursing. This paper provides an overview of forensic psychiatric care of adolescent patients. It describes the juvenile justice system, identifies various theoretical models useful for understanding youthful offenders, and explores risk and protective factors. Psychiatric comorbidities and treatment considerations also are presented. PMID- 28985121 TI - THE COUNSELOR'S HANDBOOK: A PRACTICAL A?Z GUIDE TO PROFESSIONAL AND CLINICAL PRACTICE. PMID- 28985122 TI - USING CREATIVE ARTS TO BUILD COPING SKILLS TO REDUCE DOMESTIC VIOLENCE IN THE LIVES OF FEMALE JUVENILE OFFENDERS. AB - The development of gender-specific programming is gaining attention as the approach that most effectively addresses the needs of female youthful offenders. This study provides a profile of female juvenile offenders, their problems and needs, and suggests psychoeducational approaches for building coping skills to reduce cycles of domestic violence. This is particularly important within a system designed primarily for their male counterparts. PMID- 28985123 TI - THE ROLE OF CONTEXTUAL, CHILD, AND PARENT FACTORS IN PREDICTING CRIMINAL OUTCOMES IN ADOLESCENCE. AB - This study examined predictor variables that would contribute toward an explanatory model linking child maltreatment and the outcome of crime seriousness. A secondary data analysis was completed on a random sample of youth committed and detained by a juvenile justice system in the northeast United States. Although existing data indicate a predisposition to crime and violence among youth that are maltreated, more research is needed to determine the exact nature of the link, as well as the need to determine the relationship of associated factors. The aim of this analysis was to identify key contextual, child, and parental factors related to maladaptive behavior in abused and neglected adolescent offenders. Logistic regression was used to predict serious criminal outcomes. Overall, 73% of the cases were correctly classified. Ten variables remained in the model to predict serious juvenile criminal behavior. Youth who had been exposed to community violence or who had a mother with mental illness were four times as likely to commit serious criminal behaviors. PMID- 28985124 TI - FROM THE GUEST EDITOR OF THIS SPECIAL ISSUE ON YOUTHFUL OFFENDERS. PMID- 28985125 TI - Progressive Changes in Walking Kinematics and Kinetics After Anterior Cruciate Ligament Injury and Reconstruction: A Review and Meta-Analysis. AB - CONTEXT: Anterior cruciate ligament (ACL) injury and ACL reconstruction (ACLR) result in persistent alterations in lower extremity movement patterns. The progression of lower extremity biomechanics from the time of injury has not been described. OBJECTIVE: To compare the 3-dimensional (3D) lower extremity kinematics and kinetics of walking among individuals with ACL deficiency (ACLD), individuals with ACLR, and healthy control participants from 3 to 64 months after ACLR. DATA SOURCES: We searched PubMed and Web of Science from 1970 through 2013. STUDY SELECTION AND DATA EXTRACTION: We selected only articles that provided peak kinematic and kinetic values during walking in individuals with ACLD or ACLR and comparison with a healthy control group or the contralateral uninjured limb. DATA SYNTHESIS: A total of 27 of 511 identified studies were included. Weighted means, pooled standard deviations, and 95% confidence intervals were calculated for the healthy control, ACLD, and ACLR groups at each reported time since surgery. The magnitude of between-groups (ACLR versus ACLD, control, or contralateral limb) differences at each time point was evaluated using Cohen d effect sizes and associated 95% confidence intervals. Peak knee flexion angle (Cohen d = -0.41) and external knee-extensor moment (Cohen d = 0.68) were smaller in the ACLD than in the healthy control group. Peak knee flexion angle (Cohen d range = -0.78 to -1.23) and external knee-extensor moment (Cohen d range = -1.39 to -2.16) were smaller in the ACLR group from 10 to 40 months after ACLR. Reductions in external knee-adduction moment (Cohen d range = 0.50 to -1.23) were present from 9 to 42 months after ACLR. CONCLUSIONS: Reductions in peak knee-flexion angle, external knee-flexion moment, and external knee-adduction moment were present in the ACLD and ACLR groups. This movement profile during the loading phase of gait has been linked to knee-cartilage degeneration and may contribute to the development of osteoarthritis after ACLR. PMID- 28985129 TI - Erratum: IJSPP 12(6), 2017. AB - The preceding issue of the journal, IJSPP 12(6), was marked incorrectly in print only on the cover and on the table of contents page as a June issue when it was, in fact, the July issue. The online issue is and always has been correct; only the print version was affected. PMID- 28985130 TI - Is There Risk in Exercise Testing of Athletes? PMID- 28985131 TI - Spot Sample Urine Specific Gravity Does Not Accurately Represent Small Decreases in Plasma Volume in Resting Healthy Males. AB - BACKGROUND: Urine specific gravity (USG) is often used to assess hydration status, particularly around athletic competition, but it is unknown whether high USG is indicative of plasma volume (PV) reduction (i.e., hypohydration). We tested the hypothesis that if high USG is reflective of reduced PV, subsequent fluid ingestion would increase PV. PURPOSE: The purpose of this study was to examine 24-hour changes in USG and PV in individuals presenting with high and low spot USG. METHODS: Nineteen healthy males were provided food and water over 24 hours with a total water volume of 35 ml.kg-1 body mass. Absolute PV and blood volume (BV), measured using the CO-rebreathe technique, along with USG were measured before and after a 24-hour intervention period. Based on a preintervention morning spot USG, subjects were post hoc assigned to groups according to USG (<=1.020 or >1.020; low and high USG, respectively). RESULTS: Despite presenting with an elevated spot USG (1.026 +/- 0.004), subsequent fluid ingestion over 24 hours did not lead to changes (?) in PV (-75 +/- 234 ml) or BV (-156 +/- 370 ml) in the high USG group (p > 0.05). However, a spot USG after the 24-hour intervention in this group decreased (p = 0.018) to a level indicating improved hydration status (1.017 +/- 0.007). In the low USG group, there were no changes in PV (-39 +/- 274 ml), BV (-82 +/- 396 ml), or USG (0.003 +/- 0.007) over the 24-hour fluid intervention (all p > 0.05). CONCLUSIONS: Despite a high preintervention USG and subsequent decrease after 24-hour fluid intake, measures of PV and BV were not indicative of this seemingly improved hydration status. This suggests that a highly concentrated spot sample USG and subsequent changes are not accurately representative of PV or BV. PMID- 28985132 TI - ENT3 utilizes a pH Sensing Mechanism for Transport. PMID- 28985134 TI - Is the Simple Saline Mount Technique More Effective than Potassium Hydroxide for the Microscopic Detection of Sarcoptes scabiei? PMID- 28985133 TI - Organ Doses Associated with Partial-Body Irradiation with 2.5% Bone Marrow Sparing of the Non-Human Primate: A Retrospective Study. AB - A partial-body irradiation model with approximately 2.5% bone marrow sparing (PBI/BM2.5) was established to determine the radiation dose-response relationships for the prolonged and delayed multi-organ effects of acute radiation exposure. Historically, doses reported to the entire body were assumed to be equal to the prescribed dose at some defined calculation point, and the dose-response relationship for multi-organ injury has been defined relative to the prescribed dose being delivered at this point, e.g., to a point at mid-depth at the level of the xiphoid of the non-human primate (NHP). In this retrospective dose study, the true distribution of dose within the major organs of the NHP was evaluated, and these doses were related to that at the traditional dose prescription point. Male rhesus macaques were exposed using the PBI/BM2.5 protocol to a prescribed dose of 10 Gy using 6-MV linear accelerator photons at a rate of 0.80 Gy/min. Point and organ doses were calculated for each NHP from computed tomography (CT) scans using heterogeneous density data. The prescribed dose of 10.0 Gy to a point at midline tissue assuming homogeneous media resulted in 10.28 Gy delivered to the prescription point when calculated using the heterogeneous CT volume of the NHP. Respective mean organ doses to the volumes of nine organs, including the heart, lung, bowel and kidney, were computed. With modern treatment planning systems, utilizing a three-dimensional reconstruction of the NHP's CT images to account for the variations in body shape and size, and using density corrections for each of the tissue types, bone, water, muscle and air, accurate determination of the differences in dose to the NHP can be achieved. Dose and volume statistics can be ascertained for any body structure or organ that has been defined using contouring tools in the planning system. Analysis of the dose delivered to critical organs relative to the total-body target dose will permit a more definitive analysis of organ-specific effects and their respective influence in multiple organ injury. PMID- 28985128 TI - National Athletic Trainers' Association Position Statement: Fluid Replacement for the Physically Active. AB - OBJECTIVE: To present evidence-based recommendations that promote optimized fluid-maintenance practices for physically active individuals. BACKGROUND: Both a lack of adequate fluid replacement (hypohydration) and excessive intake (hyperhydration) can compromise athletic performance and increase health risks. Athletes need access to water to prevent hypohydration during physical activity but must be aware of the risks of overdrinking and hyponatremia. Drinking behavior can be modified by education, accessibility, experience, and palatability. This statement updates practical recommendations regarding fluid replacement strategies for physically active individuals. RECOMMENDATIONS: Educate physically active people regarding the benefits of fluid replacement to promote performance and safety and the potential risks of both hypohydration and hyperhydration on health and physical performance. Quantify sweat rates for physically active individuals during exercise in various environments. Work with individuals to develop fluid-replacement practices that promote sufficient but not excessive hydration before, during, and after physical activity. PMID- 28985136 TI - Same behavior, different provider: American medical students' attitudes toward reporting risky behaviors committed by doctors, nurses, and classmates. AB - The bioethics literature lacks findings about medical students' attitudes toward reporting risky behaviors that can cause error or reduce the perceived quality of health care. A survey was administered to 159 medical students to assess their likelihood to directly approach and to report various providers-a physician, nurse, or medical student-for three behaviors (poor hand hygiene, intoxication, or disrespect of patients). For the same behavior, medical students were significantly more likely to approach a classmate, followed by a nurse and then a doctor (p < .0001), to ask for behavioral modification. Across all three health care provider types, medical students were most likely to report intoxication (p < .0001). Medical students' willingness to approach or report a provider for a risky or unprofessional behavior is influenced by the type of health care provider in question. Medical schools should implement patient safety curricula that alleviate fears about reporting superiors and create anonymous reporting systems to improve reporting rates. PMID- 28985137 TI - Principles of Quantitative MR Imaging with Illustrated Review of Applicable Modular Pulse Diagrams. AB - Continued improvements in diagnostic accuracy using magnetic resonance (MR) imaging will require development of methods for tissue analysis that complement traditional qualitative MR imaging studies. Quantitative MR imaging is based on measurement and interpretation of tissue-specific parameters independent of experimental design, compared with qualitative MR imaging, which relies on interpretation of tissue contrast that results from experimental pulse sequence parameters. Quantitative MR imaging represents a natural next step in the evolution of MR imaging practice, since quantitative MR imaging data can be acquired using currently available qualitative imaging pulse sequences without modifications to imaging equipment. The article presents a review of the basic physical concepts used in MR imaging and how quantitative MR imaging is distinct from qualitative MR imaging. Subsequently, the article reviews the hierarchical organization of major applicable pulse sequences used in this article, with the sequences organized into conventional, hybrid, and multispectral sequences capable of calculating the main tissue parameters of T1, T2, and proton density. While this new concept offers the potential for improved diagnostic accuracy and workflow, awareness of this extension to qualitative imaging is generally low. This article reviews the basic physical concepts in MR imaging, describes commonly measured tissue parameters in quantitative MR imaging, and presents the major available pulse sequences used for quantitative MR imaging, with a focus on the hierarchical organization of these sequences. (c)RSNA, 2017. PMID- 28985135 TI - Whole-Body Diffusion-weighted MR Imaging of Iron Deposits in Hodgkin, Follicular, and Diffuse Large B-Cell Lymphoma. AB - Purpose To analyze the frequency and distribution of low-signal-intensity regions (LSIRs) in lymphoma lesions and to compare these to fluorodeoxyglucose (FDG) uptake and biologic markers of inflammation. Materials and Methods The authors analyzed 61 untreated patients with a bulky lymphoma (at least one tumor mass >=7 cm in diameter). When a LSIR within tumor lesions was detected on diffusion weighted images obtained with a b value of 50 sec/mm2, a T2-weighted gradient echo (GRE) sequence was performed and calcifications were searched for with computed tomography (CT). In two patients, Perls staining was performed on tissue samples from the LSIR. LSIRs were compared with biologic inflammatory parameters and baseline FDG positon emission tomography (PET)/CT parameters (maximum standardized uptake value [SUVmax], total metabolic tumor volume [TMTV]). Results LSIRs were detected in 22 patients and corresponded to signal void on GRE images; one LSIR was due to calcifications, and three LSIRS were due to a recent biopsy. In 18 patients, LSIRs appeared to be related to focal iron deposits; this was proven with Perls staining in two patients. The LSIRs presumed to be due to iron deposits were found mostly in patients with aggressive lymphoma (nine of 26 patients with Hodgkin lymphoma and eight of 20 patients with diffuse large B-cell lymphoma vs one of 15 patients with follicular lymphoma; P = .047) and with advanced stage disease (15 of 18 patients). LSIRS were observed in spleen (n = 14), liver (n = 3), and nodal (n = 8) lesions and corresponded to foci FDG uptake, with mean SUVmax of 9.8, 6.7, and 16.2, respectively. These patients had significantly higher serum levels of C-reactive protein, alpha1-globulin, and alpha2-globulin and more frequently had microcytic anemia than those without such deposits (P = .0072, P = .003, P = .0068, and P < .0001, respectively). They also had a significantly higher TMTV (P = .0055) and higher levels of spleen involvement (P < .0001). Conclusion LSIRs due to focal iron deposits are detected in lymphoma lesions and are associated with a more pronounced biologic inflammatory syndrome. (c) RSNA, 2017 Online supplemental material is available for this article. PMID- 28985138 TI - Optimal Combination of Soy, Buffalo, and Cow's Milk in Bioyogurt for Optimal Chemical, Nutritional, and Health Benefits. AB - OBJECTIVE: Soy milk is enriched with nutritive elements such as proteins, unsaturated fatty acids, lecithins, isoflavones, mineral substances, free amino acids, and polypeptides. The aim of this study was to increase the health and nutritional values of bioyogurt by using ABT-5 culture and mixing soy milk with buffalo and cow's milk. METHODS: Five treatments of yogurt were made from soy, buffalo, and cow's milk and from 75% buffalo + 25% soy milk mixture and 75% cow + 25% soy milk mixture using ABT-5 culture. RESULTS: Utilization of soy milk in yogurt production decreased acidity, redox potential (Eh), total solids (TS), fat, total nitrogen, ash, total volatile fatty acids (TVFAs), saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and total amino acids contents. In contrast, the highest levels of unsaturated fatty acids (USFAs), polyunsaturated fatty acids (PUFAs), linoleic acid, and alpha-linolenic acid were detected. Higher numbers of L. acidophilus and bifidobacteria were found in soy milk yogurt than in buffalo or cow's milk. Blending of buffalo or cow's milk with soy milk increased the sensory evaluation scores of yogurt. CONCLUSIONS: Mixtures of 25% soy milk + 75% buffalo milk, 25% soy milk + 75% cow's milk and ABT-5 culture could be successfully used in production of bioyogurt characterized by high health and nutritional properties. These optimal combinations highly enhanced probiotic bacteria. The recommended level of 107 cfu.g-1 of bifidobacteria as a probiotic was exceeded for soy milk yogurt treatments. PMID- 28985139 TI - Lung Cancer Risk from Plutonium: A Pooled Analysis of the Mayak and Sellafield Worker Cohorts. AB - In this study, lung cancer risk from occupational plutonium exposure was analyzed in a pooled cohort of Mayak and Sellafield workers, two of the most informative cohorts in the world with detailed plutonium urine monitoring programs. The pooled cohort comprised 45,817 workers: 23,443 Sellafield workers first employed during 1947-2002 with follow-up until the end of 2005 and 22,374 Mayak workers first employed during 1948-1982 with follow-up until the end of 2008. In the pooled cohort 1,195 lung cancer deaths were observed (789 Mayak, 406 Sellafield) but only 893 lung cancer incidences (509 Mayak, 384 Sellafield, due to truncated follow-up in the incidence analysis). Analyses were performed using Poisson regression models, and were based on doses derived from individual radiation monitoring data using an updated dose assessment methodology developed in the study. There was clear evidence of a linear association between cumulative internal plutonium lung dose and risk of both lung cancer mortality and incidence in the pooled cohort. The pooled point estimates of the excess relative risk (ERR) from plutonium exposure for both lung cancer mortality and incidence were within the range of 5-8 per Gy for males at age 60. The ERR estimates in relationship to external gamma radiation were also significantly raised and in the range 0.2-0.4 per Gy of cumulative gamma dose to the lung. The point estimates of risk, for both external and plutonium exposure, were comparable between the cohorts, which suggests that the pooling of these data was valid. The results support point estimates of relative biological effectiveness (RBE) in the range of 10-25, which is in broad agreement with the value of 20 currently adopted in radiological protection as the radiation weighting factor for alpha particles, however, the uncertainty on this value (RBE = 21; 95% CI: 9-178) is large. The results provide direct evidence that the plutonium risks in each cohort are of the same order of magnitude but the uncertainty on the Sellafield cohort plutonium risk estimates is large, with observed risks consistent with no plutonium risk, and risks five times larger than those observed in the Mayak cohort. PMID- 28985141 TI - Disclosure in traumatic deaths as correlates of differential mental health outcomes. AB - This analysis addresses the controversial question of whether disclosure of a significant other's traumatic death cause is associated with mental health outcomes. Consistent with the limited previous research, this data, collected from 131 suicide bereaved, 10 exclusively drug death bereaved, and six other bereaved respondents, showed fewer grief difficulties and better self-rated mental health among those inclined to openly disclose a significant other's death cause, compared to those who feared incurring shame and embarrassment from doing so. Regression analyses suggested that the tendency to openly discuss the death was the single most powerful correlate to explaining variations in grief difficulties. PMID- 28985140 TI - Inflammatory bactericidal lectin RegIIIbeta: Friend or foe for the host? AB - In the inflamed gut, the bactericidal lectin RegIIIbeta is massively produced by intestinal mucosa. RegIIIbeta binds peptidoglycan and lipid A respectively, and thus can kill certain Gram-positive and Gram-negative bacteria, including the gut commensal microbiota and enteropathogenic bacteria. Considering the expression pattern and bactericidal activity, RegIIIbeta is believed to be a host defense factor for protecting against the infection with enteropathogenic bacteria. However, it was poorly understood how RegIIIbeta recognizes the target bacteria and kill them, and how RegIIIbeta plays role(s) in infectious diarrhea. Therefore, our recent study has focused on RegIIIbeta-target recognition, killing of Gram-negative bacteria, and host protective functions of RegIIIbeta for infectious diarrhea inflicted by Salmonella Typhimurium. Here, we discuss novel insights into the protective role of RegIIIbeta in infectious diarrhea, and propose avenues towards novel therapeutic interventions for Salmonella diarrhea. PMID- 28985142 TI - Sour Cherries but Not Apples Added to the Regular Diet Decrease Resting and fMLP Stimulated Chemiluminescence of Fasting Whole Blood in Healthy Subjects. AB - OBJECTIVE: Berry fruits rich in anthocyanins have antioxidant and anti inflammatory properties. Blood phagocytes are an important source of oxidants that contribute to inflammatory response and oxidative stress. We examined the effect of sour cherry consumption on luminol-enhanced whole blood chemiluminescence (LBCL) reflecting oxidants generation by circulating phagocytes in healthy subjects. METHODS: Thirty-four and 29 healthy subjects (on a regular diet) consumed 500 g of sour cherries containing 346.5 mg of total anthocyanins or 500 g of anthocyanin-free apples everyday (between 1100 and 1400 hours) for 30 days. Twenty-four volunteers without any dietary intervention served as the control with respect to LBCL changes over the study period. Fasting blood and spot morning urine samples were collected before and after the fruit courses and after the 10-day wash-out period to measure resting and agonist (fMLP)-induced LBCL, blood cell count, concentration of various phenolics, and plasma antioxidant activity. RESULTS: Sour cherries inhibited (p < 0.05) median resting LBCL (by 29.5% and 33.7%) and fMLP-LBCL (by 24.7% and 32.3%) after 30-day consumption and after 10-day wash-out, respectively. No changes in LBCL were noted in the apple consumers and controls. Increased urinary levels of chlorogenic, 4-hydroxyhippuric, and 3-hydroxyhippuric acids occasionally correlated negatively with resting and fMLP-LBCL in sour cherry consumers. Other measured variables did not change in all groups over the study period. CONCLUSIONS: The inhibition of resting and agonist-induced LBCL suggests that regular sour cherry consumption may suppress the formation of reactive oxygen species by circulating phagocytes and decrease the risk of systemic imbalance between oxidants and antioxidants. This may be attributed to the anthocyanins in sour cherry and be one of mechanisms of the health-promoting effects of consumption of anthocyanin-rich fruits. PMID- 28985143 TI - Bereavement grief: A population-based foundational evidence study. AB - Information is needed on the incidence and prevalence of bereavement grief, and factors associated with severe or prolonged grief. Among 1,208 representative Canadian adults, 96% had experienced bereavement grief and 78% were actively grieving at interview. Grief levels were higher among women, Protestants, and Catholics, when the death was under 2 years previously, when a spouse, parent, or child had died, and when the perceived death quality was lower. This study reveals the importance of good deaths; they are essential for dying people and also those who mourn their deaths. PMID- 28985144 TI - The invasion of circRNAs. PMID- 28985145 TI - Virulence Profile: Renate Konig. PMID- 28985146 TI - Identification of Delta1-pyrroline 5-carboxylate synthase (P5CS) genes involved in the synthesis of proline in Lotus japonicus. AB - Proline accumulation is a common response of plants to different biotic and abiotic stresses. In the model legume Lotus japonicus, osmotic stress-induced proline accumulation is one of the first responses of the plant, converting proline in a reliable stress marker. The main biosynthetic pathway of proline is from glutamate and the reaction catalyzed by the enzyme Delta1-pyrroline 5 carboxylate synthase (P5CS) is the rate limiting step. L. japonicus has been suggested to have three different P5CS genes. Here the predicted P5CS genes of L. japonicus were analyzed in silico and their expression under osmotic stress was determined. Contrary to previous suggestions this study demonstrated that L. japonicus has two different P5CS genes, as most dicotyledonous plants do. The gene that is inducible by osmotic stress and is located on chromosome 1, was called LjP5CS1, and the one located on chromosome 2 and not inducible by osmotic stress was called LjP5CS2. PMID- 28985147 TI - Social support following bereavement: The role of beliefs, expectations, and support intentions. AB - Social support is one of the strongest determinants of bereavement outcomes, yet little is understood about the community's recognition of grief and intentions to provide social support to grieving persons. A total of 476 adults responded to an online vignette and questionnaire measuring grief norms and supportive intentions. Respondent gender, age, and bereavement status all had some association with expectations of grief, intentions to support, perceived helpfulness of support attempts, and opinions toward the diagnostic classification of grief. Given that most bereavement support is informal, this study informs the development of community capacity to provide constructive, timely bereavement support. PMID- 28985148 TI - PHYTOCHROME INTERACTING FACTORs from Physcomitrella patens are active in Arabidopsis and complement the pif quadruple mutant. AB - Phytochromes are red/far-red light receptors in plants involved in the regulation of growth and development in response to changes in the ambient environment. An important mode of action of plant phytochromes depends on their light-regulated relocation from the cytosol into the nucleus and control of gene expression; in addition, there is also evidence for a cytosolic or plasma membrane associated function of phytochromes in different species. The PHYTOCHROME INTERACTING FACTORs (PIFs) form a subgroup of the bHLH transcription factors and it is well established that PIFs are key components of phytochrome downstream signalling in the nucleus of seed plants. Recent studies identified members of the PIF family also in the liverwort Marchantia polymorpha and the moss Physcomitrella patens. Here, we show that all four potential PIF homologs from Physcomitrella have PIF function when expressed in the Arabidopsis pifQ mutant, which is deficient in multiple PIFs. We propose that PIFs are ancient components of nuclear phytochrome signalling that have emerged in the last common ancestor of today's land plants. PMID- 28985149 TI - The Moderating Effect of Interaction Avoidance Between Abusive Supervision and Subordinates' Job Promotions. AB - While abusive supervision is shown to have negative stress-related effects on targets, less is known about the factors capable of mitigating these negative effects and their career-related outcomes. In this paper, we drew on the transactional model of stress and coping (Lazarus & Folkman, 1986) and the upward mobility theory (Turner, 1960) to explore the moderating effect of subordinates' interaction avoidance between abusive supervision and job promotions. To test this moderating effect, we collected data from 604 full-time employees at three points in time over a 12-month time period in Japan. The findings suggest that interaction avoidance moderates the relationship between abusive supervision and promotions, such that this relationship will be less negative as interaction avoidance increases. PMID- 28985150 TI - Nonlinear Associations Between Co-Rumination and Both Social Support and Depression Symptoms. AB - Co-ruminating about one's problems appears to involve both beneficial self disclosure and harmful rumination, suggesting that moderate levels may be the most adaptive. This study used nonlinear regression to determine whether moderate levels of self-reported co-rumination in relationships with a sibling, parent, friend, and romantic partner are linked to the highest levels of self-perceived social support and lowest levels of self-reported depression symptoms in 175 emerging adults (77% female; M = 19.66 years). As expected, moderate co rumination was associated with high social support across all four relationship types, but, somewhat unexpectedly, high levels of co-rumination were also associated with high social support. As predicted, moderate levels of co rumination with friends and siblings were associated with low levels of depression. Contrary to hypotheses, high levels of co-rumination were associated with high depression within romantic relationships. Co-rumination with a parent did not have a linear or quadratic association with depression. These findings suggest that high co-ruminating in supportive relationships and to a lesser extent low co-ruminating in unsupportive relationships are maladaptive interpersonal processes but that co-rumination's relation to depression depends on the co-ruminating partner. Psychotherapies for depression may target these maladaptive processes by supporting clients' development of balanced self-focused negative talk. PMID- 28985151 TI - A Randomized Pilot Study of a Phone-Based Mindfulness and Weight Loss Program. AB - This study evaluated the feasibility and efficacy of integrating mindfulness training into a phone-based weight loss program to improve outcomes in those with high levels of emotional eating. Participants were 75 enrollees into an employer sponsored weight loss program who reported high levels of overeating in response to thoughts and feelings. Seventy-five overweight and obese participants (92% female, 65% Caucasian, aged 26 to 68 years) were randomized to the new mindfulness weight loss program (n = 50) or the standard behavioral weight loss program (n = 25). Both programs consisted of 11 coaching calls with health coaches and registered dietitians with supplemental online materials. Satisfaction, engagement, and percent weight lost did not significantly differ for intervention vs. control at six months. Intervention participants had significantly better scores at six-month follow-up on mindful eating, binge eating, experiential avoidance, and one mindfulness subscale. Exploratory analyses showed that improvements on several measures predicted more weight loss in the intervention group. This pilot study found that integrating mindfulness into a brief phone-based behavioral weight loss program was feasible and acceptable to participants, but did not produce greater weight loss on average, despite hypothesized changes in mindful eating. Only one third of intervention participants reported participating in mindfulness exercises regularly. Mechanisms of change observed within the intervention group suggest that for adults with high levels of emotional eating those who embrace mindful eating and meditation may lose more weight with a mindfulness intervention. PMID- 28985152 TI - Connecting in the Twitterverse: Using Twitter to satisfy unmet belonging needs. AB - The current study explored how social media can satisfy unmet needs for belonging. We predicted that, of those who experience chronic ostracism (feeling excluded and ignored frequently), people high in need to belong would utilize Twitter to satisfy their unmet belonging needs more than those low in need to belong. Specifically, individuals high in need to belong and chronic ostracism should use Twitter to form and maintain parasocial relationships (one-sided relationships with media figures). Participants (n = 315) completed a survey assessing their chronic ostracism experiences, dispositional need to belong, and Twitter behavior, particularly regarding potential parasocial relationship targets (n = 229). As expected, when participants reported experiencing high rates of chronic ostracism, participants high in need to belong used Twitter more than those low in need to belong, particularly following more parasocial relationship targets. Thus, maintaining parasocial relationships on Twitter may be an effective way to satisfy unmet belonging needs. PMID- 28985153 TI - Profiling Movement and Gait Quality Characteristics in Pre-School Children. AB - There is a dearth of suitable metrics capable of objectively quantifying motor competence. Further, objective movement quality characteristics during free play have not been investigated in pre-school children. The aims of this study were to characterize children's free play physical activity and investigate how gait quality characteristics cluster with free play in pre-school children (3-5 years old). Sixty-one children (39 boys; 4.3 +/- 0.7 years, 1.04 +/- 0.05 m, 17.8 +/- 3.2 kg) completed the movement assessment battery for children and took part in free play while wearing an ankle- and hip-mounted accelerometer. Characteristics of movement quality were profiled using a clustering algorithm. Spearman's rho and the Mann-Whitney U tests were used to assess relationships between movement quality characteristics and motor competence classification differences in integrated acceleration and spectral purity, respectively. Significant differences were found between motor competency classifications for spectral purity and integrated acceleration (p < .001). Spectral purity was hierarchically clustered with motor competence and integrated acceleration. Significant positive correlations were found between spectral purity, integrated acceleration and motor competence (p < .001). This is the first study to report spectral purity in pre-school children and the results suggest that the underlying frequency component of movement is clustered with motor competence. PMID- 28985154 TI - Rate of Torque Development and Feedforward Control of the Hip and Knee Extensors: Gender Differences. AB - The purpose of this study was to determine whether women demonstrate decreased rate of torque development (RTD) of the hip and knee extensors and altered onset timing of the vastus lateralis and gluteus maximus during a drop-jump task when compared with men. On average, women demonstrated significantly lower normalized RTD of the hip extensors (women: 11.6 +/- 1.3 MVT.s-1, men: 13.1 +/- 0.9 MVT.s-1; p <= .01); however, there was no significant difference in knee extensor RTD. Women also demonstrated significantly earlier activation of their vastus lateralis (women: 206.0 +/- 130.6 ms, men: 80.9 +/- 69.6 ms; p <= .01) and gluteus maximus (women: 85.7 +/- 58.6 ms, men: 54.5 +/- 35.4 ms; p = .02). In both men and women, there was a significant negative correlation between the hip extensor RTD and the vastus lateralis electromyographic onset time (men: r = .386, p = .046; women: r = -.531, p = .008). The study findings suggest that women may utilize a feedforward control strategy in which they activate their knee extensors earlier than men to compensate for deficits in hip extensor RTD. The impaired capacity to rapidly stabilize the hip and knee joints during dynamic maneuvers may contribute to the increased risk of anterior cruciate ligament injury observed in women. PMID- 28985155 TI - Exploring the Relationship Between Autistic Traits and Body Image, Body Satisfaction, and Body Competence. AB - Autism spectrum disorders (ASD) have been linked to bodily disorders (anorexia nervosa, obesity), and individuals with ASD are known to experience unique bodily states (e.g., exaggerated interoceptive sensitivity). Though there is evidence to suggest body variables may significantly impact quality of life in those with ASD, research has yet to examine the potential relationship between ASD and body image variables, that is, the evaluation of one's body. The present study examined 80 healthy college students (40 male, 40 female) who completed an online set of questionnaires regarding body image and satisfaction, body competency, depression, anxiety, and autistic traits (Autism Spectrum Quotient, or AQ) (Baron Cohen, Wheelwright, Skinner, Martin, & Clubley, 2001 ). Of primary interest was whether AQ scores, gender, and the interaction between AQ scores and gender could successfully predict participants' scores on body image, satisfaction, and competency scales. Autistic traits were only a significant predictor of scores on one measure of momentary body image and satisfaction (Body Image States Scale: Cash et al., 2002 ). However, our results did suggest the possibility of an interaction between gender and AQ scores in predicting reports of body image, satisfaction, and competency. PMID- 28985156 TI - Barriers to Accessing Detox Facilities, Substance Use Treatment, and Residential Services among Women Impacted by Commercial Sexual Exploitation and Trafficking. AB - More than 50% of women entering substance use treatment in the United States reported having traded sex for money or drugs. Women's participation in addiction treatment and related services is essential to their recovery and increased safety, stabilization, and quality of life. This article's aim is to explore the barriers related to accessing detox facilities and essential services including substance use treatment and residential services for women impacted by commercial sexual exploitation (CSE). Data are drawn from a larger, community-based, grounded theory study. In-depth interview data were collected from 30 adult women who traded sex as adults (through maximum variation and snowball sampling), as well as 20 service providers who come into contact with adult women who trade sex (through nominations and purposive sampling). Finding suggest that women often encountered sobriety requirements, which created barriers to accessing addiction treatment or residential services. Some organizations' policies required evicting women if they were caught using, which created additional challenges for women who relapsed. Women wanted to avoid becoming "dopesick" on the streets or at home, which partially contributed to them needing to maintain their addiction. Consequently, some returned to sex trading, thus increasing their risk of trafficking. Some women engaged in creative strategies, such as claiming they were suicidal, in order to access the detox facilities in hospitals. Some women indicated they were only able to detox when they were forced to do so in jail or prison, often without medical assistance. Implications to improve health care delivery for this population are discussed. PMID- 28985157 TI - Dyad Practice Impacts Self-Directed Practice Behaviors and Motor Learning Outcomes in a Contextual Interference Paradigm. AB - We studied dyad practice to determine whether and how alternating practice blocks with a partner impacts self-directed practice scheduling, learning, and perceptions of practice. Participants were assigned to be Partner 1 (P1) or 2 (P2). P1s had a blocked, random, or self-directed schedule, while all P2s self directed practice of 3, differently-timed keystroke-sequences. P2s showed both own error-dependent practice (switching sequences following better performance) and partner-dependent practice, with the partner's schedule impacting sequence selection and switching frequency. A partner's schedule also impacted learning. Random practice resulted in better timing accuracy than blocked practice for both partners in an immediate and delayed retention test. These data give evidence that self-directed practice behaviors and learning outcomes are modulated by a partner's practice schedule. PMID- 28985158 TI - Association Between Chronic Pain and Leisure Time Physical Activity and Sedentary Behavior in Schoolteachers. AB - Chronic pain (CP) is a public health problem with harmful social and individual effects, and its relationships with physical activity (PA) and sedentary behaviors are unclear. This study examined the relationship between CP and PA and time spent watching television as an indicator of leisure time sedentary behavior, and explored the effects of major confounding factors. The information was obtained between 2012 and 2013 from individual interviews with 943 teachers from public schools in Londrina, Brazil. Statistical analysis was performed in 2014 using a logistic regression model adjusted for sociodemographic, lifestyle, depression, and working conditions variables. The prevalence of CP was 31.9%. No statistically significant association was observed between PA and CP. In the adjusted analyses, CP was associated with time > 60 minutes/day spent watching television (odds ratio [OR] = 1.39, 95% confidence interval [CI] 1.03, 1.89) on weekdays. In analyses stratified according to body areas affected by CP, only pain in the lower limbs was associated with more time watching television (OR = 1.62, 95% CI 1.06, 2.47). Watching television on a weekday for > 60 minutes is a sedentary behavior associated with a greater likelihood of teachers having chronic pain, especially in the lower limbs. This association was observed independently of the main confounders such as sex, age, leisure time physical activity, depression and working conditions. PMID- 28985160 TI - Development and Characterization of 12 Novel Polymorphic Microsatellite Loci for the Mammal Chewing Louse Geomydoecus aurei (Insecta: Phthiraptera) and a Comparison of Next-Generation Sequencing Approaches for Use in Parasitology. AB - Next-generation sequencing methodologies open the door for evolutionary studies of wildlife parasites. We used 2 next-generation sequencing approaches to discover microsatellite loci in the pocket gopher chewing louse Geomydoecus aurei for use in population genetic studies. In one approach, we sequenced a library enriched for microsatellite loci; in the other approach, we mined microsatellites from genomic sequences. Following microsatellite discovery, promising loci were tested for amplification and polymorphism in 390 louse individuals from 13 pocket gopher hosts. In total, 12 loci were selected for analysis (6 from each methodology), none of which exhibited evidence of null alleles or heterozygote deficiencies. These 12 loci showed adequate genetic diversity for population level analyses, with 3-9 alleles per locus with an average HE per locus ranging from 0.32 to 0.70. Analysis of Molecular Variance (AMOVA) indicated that genetic variation among infrapopulations accounts for a low, but significant, percentage of the overall genetic variation, and individual louse infrapopulations showed FST values that were significantly different from zero in the majority of pairwise infrapopulation comparisons, despite all 13 infrapopulations being taken from the same locality. Therefore, these 12 polymorphic markers will be useful at the infrapopulation and population levels for future studies involving G. aurei. This study shows that next-generation sequencing methodologies can successfully be used to efficiently obtain data for a variety of evolutionary questions. PMID- 28985159 TI - International standards for monoclonal antibodies to support pre- and post marketing product consistency: Evaluation of a candidate international standard for the bioactivities of rituximab. AB - The intrinsic complexity and heterogeneity of therapeutic monoclonal antibodies is built into the biosimilarity paradigm where critical quality attributes are controlled in exhaustive comparability studies with the reference medicinal product. The long-term success of biosimilars will depend on reassuring healthcare professionals and patients of consistent product quality, safety and efficacy. With this aim, the World Health Organization has endorsed the need for public bioactivity standards for therapeutic monoclonal antibodies in support of current controls. We have developed a candidate international potency standard for rituximab that was evaluated in a multi-center collaborative study using participants' own qualified Fc-effector function and cell-based binding bioassays. Dose-response curve model parameters were shown to reflect similar behavior amongst rituximab preparations, albeit with some differences in potency. In the absence of a common reference standard, potency estimates were in poor agreement amongst laboratories, but the use of the candidate preparation significantly reduced this variability. Our results suggest that the candidate rituximab standard can support bioassay performance and improve data harmonization, which when implemented will promote consistency of rituximab products over their life-cycles. This data provides the first scientific evidence that a classical standardization exercise allowing traceability of bioassay data to an international standard is also applicable to rituximab. However, we submit that this new type of international standard needs to be used appropriately and its role not to be mistaken with that of the reference medicinal product. PMID- 28985164 TI - Erratum. PMID- 28985165 TI - Balance Theory Revisited: Relationship Issue Relevance Affects Imbalance-Induced Tension in Workplace Relationships. AB - The present work applies and extends balance theory by examining the role of relevance of issue to the relationship in balance theory processes within the context of workplace relationships. In Experiment 1, a sample of working adults (N = 81) reported greater job tension when self-supervisor dissimilarity involved a relationship-relevant (vs. non-relationship) ethical dilemma. In Experiment 2, a sample of working students (N = 185) who perceived greater self-supervisor dissimilarity about workplace (vs. family) ethics reported greater job tension, and in turn, less job satisfaction and organizational commitment. Perceiving dissimilarity with a work supervisor in attitudes about relationship-relevant issues may negatively affect outcomes at work. Importantly, these experiments demonstrated that not all dissimilarity is likely to yield negative outcomes; only relationship-relevant (vs. non-relevant) dissimilarity was a catalyst for imbalance-induced tension. PMID- 28985166 TI - Reproductive health issues. PMID- 28985167 TI - The Role of Perceived Employability, Core Self-Evaluations, and Job Resources on Health and Turnover Intentions. AB - According to Conservation of Resources (COR) theory, this study investigated the explanatory role of perceived employability, over and above core self-evaluations (CSE) and job resources, in relation to different aspects of health (physical and mental) and turnover intentions. Based on data obtained from a sample of 274 Romanian blue-collar employees (59.5% men), hierarchical multiple regressions revealed that perceived employability adds a significant variance compared to variance due to CSE and job resources with respect to aspects of health and turnover. The results highlight the role of perceived employability in health - on an individual level, and in decisions to leave the organization - on an organizational level. The findings are of value because they inform organizations how to design human resources strategies in order to retain a healthy workforce. PMID- 28985168 TI - When cold-induced vasospasm is the tip of the iceberg. PMID- 28985169 TI - Cervical cancer in African American women: Optimizing prevention to reduce disparities. PMID- 28985170 TI - Is pregnancy safe after kidney transplant? PMID- 28985171 TI - Which patients with respiratory disease need long-term azithromycin? PMID- 28985172 TI - Treating Raynaud phenomenon: Beyond staying warm. AB - Raynaud phenomenon is an overactive vascular response to cold and emotional stress that results in cutaneous color changes and sensory symptoms in the digits. It can be idiopathic (primary) or secondary to another condition; the latter can be more severe and more apt to lead to ischemic complications such as digital ulceration and even loss of digits. If nonpharmacologic interventions prove inadequate, then vasodilator agents are used. PMID- 28985173 TI - Acute monocular vision loss: Don't lose sight of the differential. PMID- 28985174 TI - Disparities in cervical cancer in African American women: What primary care physicians can do. PMID- 28985175 TI - Navigating the anticoagulant landscape in 2017. AB - Several questions remain regarding anticoagulant management: What is the best strategy for managing acute venous thromboembolism? How should patients on a direct oral anticoagulant or on warfarin be managed when they need elective surgery? When is heparin bridging necessary? PMID- 28985176 TI - Diabetes medications and cardiovascular outcome trials: Lessons learned. AB - The US Food and Drug Administration's current standards require that new diabetes medications demonstrate cardiovascular safety in large, long-term trials. New drugs that have been assessed in such trials are changing the management of type 2 diabetes. PMID- 28985177 TI - Osborn waves of hypothermia. PMID- 28985178 TI - Sarcoidosis mimicking lytic osseous metastases. PMID- 28985179 TI - A new role for zinc in the brain. AB - Certain neurons in the auditory cortex release zinc to influence how the brain processes sounds. PMID- 28985180 TI - Low Prenatal Exposures to Fluoride: Are There Neurotoxic Risks for Children? PMID- 28985181 TI - Binding of bromocresol green and bromocresol purple to albumin in hemodialysis patients. AB - BACKGROUND: Colorimetric albumin assays based on binding to bromocresol purple (BCP) and bromocresol green (BCG) yield different results in chronic kidney disease. Altered dye binding of carbamylated albumin has been suggested as a cause. In the present study, a detailed analysis was carried out in which uremic toxins, acute phase proteins and Kt/V, a parameter describing hemodialysis efficiency, were compared with colorimetrically assayed (BCP and BCG) serum albumin. METHODS: Albumin was assayed using immunonephelometry on a BN II nephelometer and colorimetrically based on, respectively, BCP and BCG on a Modular P analyzer. Uremic toxins were assessed using high-performance liquid chromatography. Acute phase proteins (C-reactive protein and alpha1-acid glycoprotein) and plasma protein alpha2-macroglobulin were assayed nephelometrically. In parallel, Kt/V was calculated. RESULTS: Sixty-two serum specimens originating from hemodialysis patients were analyzed. Among the uremic toxins investigated, total para-cresyl sulfate (PCS) showed a significant positive correlation with the BCP/BCG ratio. The serum alpha1-acid glycoprotein concentration correlated negatively with the BCP/BCG ratio. The BCP/BCG ratio showed also a negative correlation with Kt/V. CONCLUSIONS: In renal insufficiency, the BCP/BCG ratio of serum albumin is affected by multiple factors: next to carbamylation, uremic toxins (total PCS) and alpha1-acid glycoprotein also play a role. PMID- 28985182 TI - GFR estimation based on standardized creatinine and cystatin C: a European multicenter analysis in older adults. AB - BACKGROUND: Although recommended by the Kidney Disease Improving Global Outcomes, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPICR) creatinine equation was not targeted to estimate glomerular filtration rate (eGFR) among older adults. The Berlin Initiative Study (BIS1CR) equation was specifically developed in older adults, and the Lund-Malmo revised (LMRCR) and the Full Age Spectrum (FASCR) equations have shown promising results in older adults. Our aim was to validate these four creatinine equations, including addition of cystatin C in a large multicenter cohort of Europeans >=70 years. METHODS: A total of 3226 individuals (2638 with cystatin C) underwent GFR measurement (mGFR; median, 44 mL/min/1.73 m2) using plasma iohexol clearance. Bias, precision (interquartile range [IQR]), accuracy (percent of estimates +/-30% of mGFR, P30), eGFR accuracy diagrams and probability diagrams to classify mGFR<45 mL/min/1.73 m2 were compared. RESULTS: The overall results of BIS1CR/CKD-EPICR/FASCR/LMRCR were as follows: median bias, 1.7/3.6/0.6/-0.7 mL/min/1.73 m2; IQR, 11.6/12.3/11.1/10.5 mL/min/1.73 m2; and P30, 77.5%/76.4%/80.9%/83.5% (significantly higher for LMR, p<0.001). Substandard P30 (<75%) was noted for all equations at mGFR<30 mL/min/1.73 m2, and at body mass index values <20 and >=35 kg/m2. LMRCR had the most stable performance across mGFR subgroups. Only LMRCR and FASCR had a relatively constant small bias across eGFR levels. Probability diagrams exhibited wide eGFR intervals for all equations where mGFR<45 could not be confidently ruled in or out. Adding cystatin C improved P30 accuracy to 85.7/86.8/85.7/88.7 for BIS2CR+CYS/CKD-EPICR+CYS/FASCR+CYS/MEANLMR+CAPA. CONCLUSIONS: LMRCR and FASCR seem to be attractive alternatives to CKD-EPICR in estimating GFR by creatinine based equations in older Europeans. Addition of cystatin C leads to important improvement in estimation performance. PMID- 28985185 TI - Preeclampsia and intrauterine growth restriction: placental disorders still not fully understood. PMID- 28985183 TI - The effect of celery (Apium graveolens L.) on fertility: A systematic review. AB - Background Fertility and infertility problems are among the complex issues in medicine. The use of herbal products in the treatment of fertility has been considered as an alternative to synthetic drugs. Celery containing known compounds can have an impact on the fertility rate. The aim of this study was to do a systematic review on conducted studies in conjunction with the celery and reproduction. Methods Required papers were searched from databases like Science direct, PubMed, Scopus, and Springer. Keywords used in this study were "Apium graveolens L.", "fertility", "reproductive system", "sperm", "testis", "delivery", "sexual hormone", "LH", "FSH", "testosterone", "semen", "male", and "female". Out of 238 collected articles (published in the period 1995 to 2015), 222 were excluded due to non-relevance and lack of access to the original article. Results The notable points were the different results seen by different researchers during different treatment periods or at different doses. Of the 16 studies reviewed in this study, 13 studies have mentioned the positive effect of celery on fertility, while three studies reported the inhibitory effects of this plant. Conclusions Celery can have protective effects against substances such as sodium valproate, propylene glycol, and diethyl phthalate causing damages to the testicular structure and spermatogenesis. In this regard, the doses used and the treatment time while using the plant must be accurately investigated. Since there are compounds such as apigenin, the celery can induce inhibitory effects on fertility in case of chronic use or high concentration. PMID- 28985184 TI - Sirolimus precipitating diabetes mellitus in a patient with congenital hyperinsulinaemic hypoglycaemia due to autosomal dominant ABCC8 mutation. AB - BACKGROUND: Sirolimus (mTOR inhibitor) is proven to be effective in children with congenital hyperinsulinism (CHI). Studies in animals suggest that sirolimus may have diabetogenic actions. However, its role in precipitating diabetes mellitus (DM) in children with CHI has not been reported. CASE PRESENTATION: A 16-year-old female with CHI due to a dominant ABCC8 gene mutation was switched from diazoxide therapy to sirolimus, due to the hypertrichosis side effect of diazoxide. She developed facial cellulitis that was treated with clarithromycin and a month later, once the infection was resolved, she was found to have persistent hyperglycaemia, and was diagnosed with DM. She was unresponsive to oral sulfonylurea therapy and is currently managed with metformin. Her mother, who had the same ABCC8 mutation, developed DM at her 30s. CONCLUSIONS: Patients with dominant ABCC8 gene mutations are prone to DM in adulthood, but Sirolimus therapy might increase the risk of developing diabetes at an early age, as this case illustrates. PMID- 28985186 TI - A self-ordered, body-centered tetragonal superlattice of SiGe nanodot growth by reduced pressure CVD. AB - Self-ordered three-dimensional body-centered tetragonal (BCT) SiGe nanodot structures are fabricated by depositing SiGe/Si superlattice layer stacks using reduced pressure chemical vapor deposition. For high enough Ge content in the island (>30%) and deposition temperature of the Si spacer layers (T > 700 degrees C), we observe the formation of an ordered array with islands arranged in staggered position in adjacent layers. The in plane periodicity of the islands can be selected by a suitable choice of the annealing temperature before the Si spacer layer growth and of the SiGe dot volume, while only a weak influence of the Ge concentration is observed. Phase-field simulations are used to clarify the driving force determining the observed BCT ordering, shedding light on the competition between heteroepitaxial strain and surface-energy minimization in the presence of a non-negligible surface roughness. PMID- 28985187 TI - Special issue on pressure-induced superconductivity in CrAs and MnP. PMID- 28985188 TI - Facile preparation of magnetic metal organic frameworks core-shell nanoparticles for stimuli-responsive drug carrier. AB - Facile synthesis of core-shell magnetic MOFs for drug delivery is of significance due to the advantages of high drug load and easy separation. In this work, magnetic metal organic frameworks (MOFs, Fe3O4-NH2@MIL101-NH2) core-shell nanoparticles were synthesized rapidly in water phase by microwave irradiation using Fe3+ and 2-amino-1,4-benzenedicarboxylate (BDC-NH2) as metal ions and ligands respectively. The resulting magnetic MOFs exhibit large surface areas (96.04 m2 g-1), excellent magnetic response (20.47 emu g-1) and large mesopore volume (22.07 cm3 g-1) along with spherical morphologies with the diameters ranging from 140-330 nm. Using doxorubicin (DOX) as a model drug, the drug loading capacity of Fe3O4-NH2@MIL101-NH2 could reach 36.02%, substantially higher than pristine MIL101-NH2. Importantly, the release of DOX could be controlled by pH as well as the meso pore size of MOFs. The cytotoxicity assay showed that the magnetic MOFs have low cytotoxicity and good biocompatibility. The results suggest great potential of the magnetic MOFs core-shell nanoparticles fabricated in this study on controlled drug release of DOX. PMID- 28985189 TI - Charge carrier transport in defective reduced graphene oxide as quantum dots and nanoplatelets in multilayer films. AB - Graphene is a breakthrough 2D material due to its unique mechanical, electrical, and thermal properties, with considerable responsiveness in real applications. However, the coverage of large areas with pristine graphene is a challenge and graphene derivatives have been alternatively exploited to produce hybrid and composite materials that allow for new developments, considering also the handling of large areas using distinct methodologies. For electronic applications there is significant interest in the investigation of the electrical properties of graphene derivatives and related composites to determine whether the characteristic 2D charge transport of pristine graphene is preserved. Here, we report a systematic study of the charge transport mechanisms of reduced graphene oxide chemically functionalized with sodium polystyrene sulfonate (PSS), named as GPSS. GPSS was produced either as quantum dots (QDs) or nanoplatelets (NPLs), being further nanostructured with poly(diallyldimethylammonium chloride) through the layer-by-layer (LbL) assembly to produce graphene nanocomposites with molecular level control. Current-voltage (I-V) measurements indicated a meticulous growth of the LbL nanostructures onto gold interdigitated electrodes (IDEs), with a space-charge-limited current dominated by a Mott-variable range hopping mechanism. A 2D intra-planar conduction within the GPSS nanostructure was observed, which resulted in effective charge carrier mobility (MU) of 4.7 cm2 V-1 s-1 for the QDs and 34.7 cm2 V-1 s-1 for the NPLs. The LbL assemblies together with the dimension of the materials (QDs or NPLs) were favorably used for the fine tuning and control of the charge carrier mobility inside the LbL nanostructures. Such 2D charge conduction mechanism and high MU values inside an interlocked multilayered assembly containing graphene-based nanocomposites are of great interest for organic devices and functionalization of interfaces. PMID- 28985190 TI - Pregnancy and the kidney transplant recipient. AB - PURPOSE OF REVIEW: The current article reviews the available literature on the incidence, complications, outcomes, and management of pregnancies in kidney transplant recipients. RECENT FINDINGS: Pregnancy can be a reasonable option for women with a kidney transplant. More than 4700 successful pregnancies have been reported after kidney transplantation. New data have emerged regarding the risk of allograft dysfunction following pregnancy. There is a lack of consensus on the optimal time for conception, immunosuppressive targets, the safety of allograft biopsy, and infection surveillance. Successful pregnancies have recently been reported in ABO-incompatible transplant recipients and recipients of combined heart-kidney transplants. SUMMARY: The ideal contraceptive method, timing of conception, immunosuppressant protocol, infection surveillance, and the method of delivery should be individualized depending on the patient's age and medical conditions. PMID- 28985191 TI - The role of parathyroidectomy in the management of secondary hyperparathyroidism. AB - PURPOSE OF REVIEW: Parathyroidectomy (PTX) is often used to treat severe secondary hyperparathyroidism (SHPT) in patients receiving maintenance dialysis. However, most evidence for the proposed benefits of PTX originates from observational studies, which cannot demonstrate causality. A reconsideration of the potential role of PTX might help guide its appropriate use. RECENT FINDINGS: Several large observational studies have suggested that PTX can reduce mortality risk. However, these studies generally suffer from bias and confounding, tempering conclusions and suggesting that the true effects of PTX may not be known. PTX has been reported to be associated with a 2% 30-day mortality, a substantial risk for what is generally an elective procedure. Additionally, biochemical control after PTX in a subset of patients may be suboptimal. The optimal surgical approach to PTX in specific clinical scenarios is also uncertain. SUMMARY: PTX may be beneficial for certain patients with severe SHPT and clinical symptoms, but identifying patients in whom the benefits are likely to outweigh the risks is a substantial challenge. Further, great care must be taken to monitor symptoms and laboratory values in patients who undergo PTX in the immediate postoperative period and, in many cases, well beyond. PMID- 28985192 TI - Incorporating supportive care into the hemodialysis unit. AB - PURPOSE OF REVIEW: Advance care planning is underutilized in patients with dialysis-dependent kidney failure and the provision of high intensity rather than supportive care is a standard practice in most hemodialysis units wherever challenges to incorporating palliative or supportive care into unit processes remain formidable. RECENT FINDINGS: The practice of advance care planning empowers patients, families and physicians and drives decisions about future treatment that align with patients' values, wishes and changing clinical circumstances. Barriers to incorporating supportive care exist; however, advance care planning optimizes the chance for future care that is smooth, compassionate, timely and supportive. SUMMARY: Care that is palliative in nature may be desired by dialysis patients suffering from escalating comorbid illness and ongoing clinical decline. Advance care planning addresses wishes for future treatment and serves as a prerequisite to the provision of patient-centered care. Nephrologists are uniquely poised to promote a culture that incorporates shared decision-making and support for palliative treatment into dialysis unit care. PMID- 28985193 TI - Medical and policy considerations for nuclear and radiation accidents, incidents and terrorism. AB - PURPOSE OF REVIEW: The purpose of this review is to address the increasing medical and public concern regarding the health consequences of radiation exposure, a concern shaped not only by fear of another Chernobyl or Fukushima nuclear power facility accident but also by the intentional use of a nuclear weapon, a radiological dispersion device, a radiological exposure device, or an improved nuclear device by rogue states such as North Korea and terrorist organizations such as Al Qaeda and ISIS. RECENT FINDINGS: The United States has the medical capacity to respond to a limited nuclear or radiation accident or incident but an effective medical response to a catastrophic nuclear event is impossible. Dealing effectively with nuclear and radiation accidents or incidents requires diverse strategies, including policy decisions, public education, and medical preparedness. SUMMARY: I review medical consequences of exposures to ionizing radiations, likely concomitant injuries and potential medical intervention. These data should help haematologists and other healthcare professionals understand the principles of medical consequences of nuclear terrorism. However, the best strategy is prevention. PMID- 28985194 TI - Current status of blood 'pharming': megakaryoctye transfusions as a source of platelets. AB - PURPOSE OF REVIEW: Donor-derived platelets have proven to be of hemostatic value in many clinical settings. There is a fear that the need for platelets may outgrow the donor pool in first-world countries. Moreover, there are other challenges with donor platelets that add to the impetus to find an alternative platelet source, especially after the megakaryocyte cytokine thrombopoietin was identified. Megakaryocytes have since been differentiated from numerous cell sources and the observed released platelet-like particles (PLPs) have led to calls to develop such products for clinical use. The development of megakaryocytes from embryonic stem cell also supported the concept of developing nondonor-based platelets. RECENT FINDINGS: Several groups have claimed that nondonor-based platelets derived from in-vitro grown megakaryocytes may soon become available to supplement or replace donor-derived products, but their number and quality has been wanting. A possible alternative of directly infusing megakaryocytes that release platelets in the lungs - similar to that recently shown for endogenous megakaryocytes - has been proposed. SUMMARY: This present review will describe the present state-of-the-art in generating and delivering nondonor-derived platelets. Progress has been slow, but advances in our ability to generate human megakaryocytes in culture, generate PLPs from these cells, and test the functionality of the resultant platelets in vitro and in vivo have identified important remaining challenges and raised alternative potential solutions. PMID- 28985195 TI - Effects of dexamethasone on early cognitive decline after cardiac surgery: A randomised controlled trial. AB - BACKGROUND: Postoperative cognitive decline (POCD), a very common complication after cardiac surgery, is characterised by impairment of both memory function and intellectual ability as well as being associated with increased use of healthcare resources. The investigators focused on the role of the inflammatory response to a surgical procedure as a potential factor involved in the pathogenesis of POCD. OBJECTIVE: The use of prophylactic dexamethasone to attenuate the inflammatory response was hypothesised to reduce the risk of POCD. DESIGN: Randomised controlled study. SETTING: Single university teaching hospital, from March 2015 to January 2016. PATIENTS: A total of 169 patients scheduled for elective cardiac surgery were enrolled, and 161 patients were included in the analyses. INTERVENTION: Patients were randomised to receive a single intravenous bolus of 0.1 mg kg dexamethasone (n = 85) or placebo (n = 84) 10 h before the surgery. MAIN OUTCOME MEASURES: The primary outcome measure in both groups was the incidence of POCD on the 6th day after surgery. The investigators also evaluated the effect of dexamethasone on the incidence of systemic inflammatory response syndrome, postoperative C-reactive protein levels and postoperative serum S100beta protein levels. RESULTS: Compared to the placebo group, the dexamethasone group showed statistically significant reductions in the incidence of POCD (relative risk, 0.43; 95% confidence interval, 0.21 to 0.89; P = 0.02), the incidence of systemic inflammatory response syndrome (30.0 versus 58.0%, P < 0.001) and postoperative C-reactive protein levels (P < 0.001). Postoperative S100beta levels were insignificantly lower (P = 0.56) in the dexamethasone group. CONCLUSION: Preoperative administration of dexamethasone reduced the inflammatory response and thereby decreased the risk of early POCD after cardiac surgery. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02767713. PMID- 28985196 TI - Inflammatory Stroma of Lymphoepithelioma-like Carcinoma of the Cervix: Immunohistochemical Study of 3 Cases and Review of the Literature. AB - The aim of this study was to characterize the inflammatory infiltrate of the lymphoepithelioma-like carcinoma, a variant of squamous cell carcinoma clinically associated with a good prognosis. Immunohistochemistry was used to characterize 3 cases of lymphoepithelioma-like carcinoma in the uterine cervix, diagnosed over a period of 3 yr. The patients were between 30 and 50 yr old. Their cervical smears had shown atypical squamous cells of unknown significance or high-grade squamous intraepithelial lesions, and the initial cervical biopsy showed high-grade cervical intraepithelial neoplasia (CIN3) or squamous cell carcinoma. All patients underwent a Wertheim operation, 2 of which were preceded by a cervicectomy. Microscopically, all tumors were characterized by poorly defined sheets of undifferentiated squamous cells with a syncytial pattern and a dense background of infiltrating lymphocytes. Immunohistochemical analysis revealed that the lymphocytes were predominantly CD3 and CD8 T cells. The tumor lobules contained isolated CD8 T cells, whereas CD4 T cells and CD20 B cells surrounded the tumor lobules. CD56 NK cells and CD79 B cells were scattered in the tumor tissue. An in situ hybridization staining for Epstein-Barr encoding region was negative but all cases were immunohistochemically positive for P16. Follow-up varied between 2 mo and 2.7 yr. All 3 patients were disease free. Lymphoepithelioma-like carcinoma of the uterine cervix is a variant of squamous cell carcinoma, known for its better prognosis. The good prognosis of this tumor is potentially explained by the high levels of infiltrating CD8 T cells. PMID- 28985198 TI - Impact of the ?El Nino Costero? phenomenon on the Peruvian population's health in 2017. PMID- 28985197 TI - Downregulation of lncRNA X Inactive Specific Transcript (XIST) Suppresses Cell Proliferation and Enhances Radiosensitivity by Upregulating mir-29c in Nasopharyngeal Carcinoma Cells. AB - BACKGROUND LncRNA X inactive specific transcript (XIST) was reported to function as an oncogene in nasopharyngeal carcinoma cells (NPC) by sponging miR-34a-5p. However, the role of XIST in modulating the radiosensitivity of NPC cells and its mechanism still remain undefined. MATERIAL AND METHODS The expressions of XIST and miR-29c in NPC cells were evaluated by qRT-PCR. CNE1 and CNE2 cells were transfected with si-XIST, pcDNA-XIST, miR-29c mimics, anti-miR-29c, or respective controls by Lipofectamine 2000. The effects of XIST knockdown and miR-29c overexpression on cell proliferation, survival fraction, and gamma-H2AX expression were investigated by CCK-8 assay, colony formation assay, immunofluorescence, and Western blot, respectively. Luciferase reporter assay and qRT-PCR analysis were performed to confirm whether XIST interacts with miR-29c and regulates its expression. RESULTS XIST was upregulated and miR-29c was downregulated in NPC cells. The expressions of XIST and miR-29c changed reversely in response to irradiation. Knockdown of XIST and miR-29c overexpression both resulted in a dramatic suppression of cell proliferation, a marked enhancement of radiosensitivity, and an obvious increase of gamma-H2AX foci formation in NPC cells. Luciferase reporter assay and qRT-PCR analysis demonstrated that XIST interacts with miR-29c and negatively regulates its expression. Moreover, miR-29c inhibition abrogated XIST knockdown-induced cell proliferation inhibition and radiosensitivity increase in NPC cells. CONCLUSIONS XIST knockdown suppressed cell proliferation and enhanced radiosensitivity of NPC cells by upregulating miR 29c, providing a novel therapeutic target to improve radiotherapy efficiency for patients with NPC. PMID- 28985199 TI - Renal lineage cells as a source for renal regeneration. AB - The mammalian kidney is a highly complex organ, composed of various cell types within a unique structural framework. Nonetheless, in recent years, giant leaps in our understanding of nephrogenesis and the origin of new cells in the adult kidney have resulted in novel routes to regenerate damaged nephrons. While several strategies can be envisioned to achieve this aim, one common theme is the reliance on renal lineage cells, as extrarenal cells, such as bone marrow-derived cells, have been shown to be devoid of renal differentiation capacity. Herein, we will present the main motivation for the pursuit for cell-based therapies, which is the ever growing problem of chronic kidney disease (CKD), and discuss different strategies toward replenishing the damaged renal parenchyma. These include transplantation of fetal kidney grafts or fetal kidney stem cells, directed differentiation of pluripotent stem cells into kidney epithelia, establishment of renal progenitors from the adult kidney, and genetic reprogramming of mature kidney cells into a progenitor state. Taken together with novel techniques recapitulating the three-dimensional developmental environment, these advances are expected to take the field into a new era, bringing us closer than ever to the day when kidney stem cell-based therapy becomes a viable therapeutic option. PMID- 28985200 TI - Cellular therapy for traumatic neurological injury. AB - Neurological injury is the primary lethal mechanism of injury in children, and the primary etiology of long-term disability after trauma. Laboratories and clinical/translational teams have sought to develop stem/progenitor cell therapies to improve recovery in a clinical setting in which there is no significant reparative option. While none of these treatments are currently standard therapeutics, phase IIb clinical trials are underway in both adults and children in severe traumatic brain injury (TBI) and phase I/IIa trials in spinal cord injury. This review will characterize the cell therapy strategies: cell replacement and tissue integration vs. immunomodulation/enhanced endogenous tissue repair. TBI is somewhat different from other central nervous system injuries (spinal cord injury and stroke), in that TBI is a diffuse injury, whereas spinal cord injury and stroke are anatomically discrete. Importantly, this drives cell therapy approaches, as TBI is less apt to be treatable with a local cell replacement intervention. More localized injuries may be more amenable to local approaches and cell replacement to bridge focal gaps. This review focuses on a few reports in the field that highlight areas of progress, but is not intended to be a comprehensive survey of the state of regenerative medicine for neurological injuries. PMID- 28985204 TI - Noncoding RNAs as effective markers in cancer-care management. PMID- 28985201 TI - "Good things come in small packages": application of exosome-based therapeutics in neonatal lung injury. AB - Infants born at very low gestational age contribute disproportionately to neonatal morbidity and mortality. Advancements in antenatal steroid therapies and surfactant replacement have favored the survival of infants with ever-more immature lungs. Despite such advances in medical care, cardiopulmonary and neurological impairment prevail in constituting the major adverse outcomes for neonatal intensive care unit survivors. With no single effective therapy for either the prevention or treatment of such neonatal disorders, the need for new tools to treat and reduce risk of further complications associated with extreme preterm birth is urgent. Mesenchymal stem/stromal cell (MSC)-based approaches have shown promise in numerous experimental models of lung injury relevant to neonatology. Recent studies have highlighted that the therapeutic potential of MSCs is harnessed in their secretome, and that the therapeutic vector therein is represented by the exosomes released by MSCs. In this review, we summarize the development and significance of stem cell-based therapies for neonatal diseases, focusing on preclinical models of neonatal lung injury. We emphasize the development of MSC exosome-based therapeutics and comment on the challenges in bringing these promising interventions to clinic. PMID- 28985202 TI - 3D bioprinting using stem cells. AB - Recent advances have allowed for three-dimensional (3D) printing technologies to be applied to biocompatible materials, cells and supporting components, creating a field of 3D bioprinting that holds great promise for artificial organ printing and regenerative medicine. At the same time, stem cells, such as human induced pluripotent stem cells, have driven a paradigm shift in tissue regeneration and the modeling of human disease, and represent an unlimited cell source for tissue regeneration and the study of human disease. The ability to reprogram patient specific cells holds the promise of an enhanced understanding of disease mechanisms and phenotypic variability. 3D bioprinting has been successfully performed using multiple stem cell types of different lineages and potency. The type of 3D bioprinting employed ranged from microextrusion bioprinting, inkjet bioprinting, laser-assisted bioprinting, to newer technologies such as scaffold free spheroid-based bioprinting. This review discusses the current advances, applications, limitations and future of 3D bioprinting using stem cells, by organ systems. PMID- 28985203 TI - Cell therapy for diverse central nervous system disorders: inherited metabolic diseases and autism. AB - The concept of utilizing human cells for the treatment of medical conditions is not new. In its simplest form, blood product transfusion as treatment of severe hemorrhage has been practiced since the 1800s. The advent of hematopoietic stem cell transplantation (HSCT) began with the development of bone marrow transplantation for hematological malignancies in the mid-1900s and is now the standard of care for many hematological disorders. In the past few decades, HSCT has expanded to additional sources of donor cells, a wider range of indications, and the development of novel cell products. This trajectory has sparked a rapidly growing interest in the pursuit of innovative cell therapies to treat presently incurable diseases, including neurological conditions. HSCT is currently an established therapy for certain neurologically devastating inherited metabolic diseases, in which engrafting donor cells provide lifelong enzyme replacement that prevents neurological deterioration and significantly extends the lives of affected children. Knowledge gained from the treatment of these rare conditions has led to refinement of the indications and timing of HSCT, the study of additional cellular products and techniques to address its limitations, and the investigation of cellular therapies without transplantation to treat more common neurological conditions, such as autism spectrum disorder. PMID- 28985205 TI - Corrigendum: Targeting CASP8 and FADD-like apoptosis regulator ameliorates nonalcoholic steatohepatitis in mice and nonhuman primates. AB - This corrects the article DOI: 10.1038/nm.4290. PMID- 28985208 TI - Mission control: Drug developers test the 'benefit corporation' business model. PMID- 28985207 TI - Erratum: Thermoneutral housing exacerbates nonalcoholic fatty liver disease in mice and allows for sex-independent disease modeling. AB - This corrects the article DOI: 10.1038/nm.4346. PMID- 28985209 TI - Erratum: Elimination of large tumors in mice by mRNA-encoded bispecific antibodies. AB - This corrects the article DOI: 10.1038/nm.4356. PMID- 28985210 TI - Engineering MeCP2 to spy on its targets. PMID- 28985206 TI - Clonal evolution in leukemia. AB - Human leukemias are liquid malignancies characterized by diffuse infiltration of the bone marrow by transformed hematopoietic progenitors. The accessibility of tumor cells obtained from peripheral blood or through bone marrow aspirates, together with recent advances in cancer genomics and single-cell molecular analysis, have facilitated the study of clonal populations and their genetic and epigenetic evolution over time with unprecedented detail. The results of these analyses challenge the classic view of leukemia as a clonal homogeneous diffuse tumor and introduce a more complex and dynamic scenario. In this review, we present current concepts on the role of clonal evolution in lymphoid and myeloid leukemia as a driver of tumor initiation, disease progression and relapse. We also discuss the implications of these concepts in our understanding of the evolutionary mechanisms involved in leukemia transformation and therapy resistance. PMID- 28985211 TI - Rationalizing combination therapies. PMID- 28985212 TI - GDF15 and energy balance: homing in on a mechanism. PMID- 28985213 TI - Corrigendum: Classification and characterization of microsatellite instability across 18 cancer types. AB - This corrects the article DOI: 10.1038/nm.4191. PMID- 28985215 TI - Angst about exclusivity: The potential cost of incentivizing makers of generic drugs. PMID- 28985216 TI - The Babesia bovis hap2 gene is not required for blood stage replication, but expressed upon in vitro sexual stage induction. AB - Babesia bovis, is a tick borne apicomplexan parasite responsible for important cattle losses globally. Babesia parasites have a complex life cycle including asexual replication in the mammalian host and sexual reproduction in the tick vector. Novel control strategies aimed at limiting transmission of the parasite are needed, but transmission blocking vaccine candidates remain undefined. Expression of HAP2 has been recognized as critical for the fertilization of parasites in the Babesia-related Plasmodium, and is a leading candidate for a transmission blocking vaccine against malaria. Hereby we identified the B. bovis hap2 gene and demonstrated that it is widely conserved and differentially transcribed during development within the tick midgut, but not by blood stage parasites. The hap2 gene was disrupted by transfecting B. bovis with a plasmid containing the flanking regions of the hap2 gene and the GPF-BSD gene under the control of the ef-1alpha-B promoter. Comparison of in vitro growth between a hap2 KO B. bovis clonal line and its parental wild type strain showed that HAP2 is not required for the development of B. bovis in erythrocytes. However, xanthurenic acid-in vitro induction experiments of sexual stages of parasites recovered after tick transmission resulted in surface expression of HAP2 exclusively in sexual stage induced parasites. In addition, hap2-KO parasites were not able to develop such sexual stages as defined both by morphology and by expression of the B. bovis sexual marker genes 6-Cys A and B. Together, the data strongly suggests that tick midgut stage differential expression of hap2 is associated with the development of B. bovis sexual forms. Overall these studies are consistent with a role of HAP2 in tick stages of the parasite and suggest that HAP2 is a potential candidate for a transmission blocking vaccine against bovine babesiosis. PMID- 28985214 TI - Cancer stem cells revisited. AB - The cancer stem cell (CSC) concept was proposed four decades ago, and states that tumor growth, analogous to the renewal of healthy tissues, is fueled by small numbers of dedicated stem cells. It has gradually become clear that many tumors harbor CSCs in dedicated niches, and yet their identification and eradication has not been as obvious as was initially hoped. Recently developed lineage-tracing and cell-ablation strategies have provided insights into CSC plasticity, quiescence, renewal, and therapeutic response. Here we discuss new developments in the CSC field in relationship to changing insights into how normal stem cells maintain healthy tissues. Expectations in the field have become more realistic, and now, the first successes of therapies based on the CSC concept are emerging. PMID- 28985218 TI - Spatial and temporal trends of visceral leishmaniasis by mesoregion in a southeastern state of Brazil, 2002-2013. AB - BACKGROUND: Visceral leishmaniasis (VL) is expanding in Brazil and in other South American countries, a process that has been associated with the urbanization of the disease. This study analyzes the spatial and temporal distribution of VL in the Brazilian state of Minas Gerais and identifies the areas with higher risks of transmission. METHODOLOGY: An ecological study with spatial and time series analyzes of new confirmed cases of VL notified to the Brazilian Notifiable Disease Information System between 2002 and 2013, considering the 12 mesoregions of Minas Gerais. Two complementary methodologies were used: thematic maps of incidence and Poisson (log-linear) generalized linear model. Thematic maps using crude and smoothed cumulative incidences were generated for four trienniums. Poisson Regression measured the variation of the average number of cases from one year to the following, for each mesoregion. PRINCIPAL FINDINGS: The 5,778 cases analyzed revealed a heterogeneous spatial and temporal distribution of VL in Minas Gerais. Six mesoregions (Central Mineira, Jequitinhonha, Metropolitan area of Belo Horizonte, Northwest of Minas, North of Minas, and Vale do Rio Doce) were responsible for the expansion and maintenance of VL, with incidence rates as high as 26/100,000 inhabitants. The Vale do Rio Doce and Jequitinhonha mesoregions showed a considerable increase in the incidence rates in the last period studied. The other six mesoregions reported only sporadic cases and presented low and unsteady incidence rates, reaching a maximum of 1.2/100,000 inhabitants. CONCLUSIONS/SIGNIFICANCE: The results contribute to further the current understanding about the expansion of VL in Minas Gerais and may help guide actions for disease control. PMID- 28985217 TI - Lymphatic filariasis transmission on Mafia Islands, Tanzania: Evidence from xenomonitoring in mosquito vectors. AB - INTRODUCTION: Lymphatic filariasis (LF) is a chronic nematode infection transmitted by mosquitoes and in sub-Saharan Africa it is caused by Wuchereria bancrofti. The disease was targeted for global elimination by 2020 using repeated community-wide mass drug administration (MDA) distributed in endemic areas. However, recently, there has been a growing recognition of the potential role of including vector control as a supplement to MDA to achieve elimination goal. This study was carried out to determine mosquito abundance and transmission of bancroftian filariasis on Mafia Islands in Tanzania as a prerequisite for a search for appropriate vector control methods to complement the ongoing MDA campaign. METHODS: Mosquitoes were collected indoor and outdoor using Centre for Disease Control (CDC) light and gravid traps, respectively. Collected mosquitoes were identified based on their differential morphological features and Anopheles gambiae complex and An. funestus group were further identified to their respective sibling species by polymerase chain reaction (PCR). Filarial mosquito vectors were then examined for infection with Wuchereria bancrofti by microscopy and PCR technique. RESULTS: Overall, a total of 35,534 filarial mosquito vectors were collected, of which Anopheles gambiae complex, An. funestus group and Culex quinquefasciatus Say accounted for 1.3, 0.5 and 98.2%, respectively. Based on PCR identification, An. gambiae sensu stricto (s.s) and An. funestus s.s sibling species accounted for 88.3% and 99.1% of the identified members of the An. gambiae complex and An. funestus group, respectively. A total of 7,936 mosquitoes were examined for infection with W. bancrofti by microscopy. The infection and infectivity rates were 0.25% and 0.08%, respectively. Using pool screen PCR technique, analysis of 324 mosquito pools (each with 25 mosquitoes) resulted to an estimated infection rate of 1.7%. CONCLUSION: The study has shown that Cx. quinquefasciatus is the dominant mosquito on Mafia Islands. By using mosquito infectivity as proxy to human infection, the study indicates that W. bancrofti transmission is still ongoing on Mafia Islands after more than a decade of control activities based on MDA. PMID- 28985219 TI - The ins and outs of vanillyl alcohol oxidase: Identification of ligand migration paths. AB - Vanillyl alcohol oxidase (VAO) is a homo-octameric flavoenzyme belonging to the VAO/PCMH family. Each VAO subunit consists of two domains, the FAD-binding and the cap domain. VAO catalyses, among other reactions, the two-step conversion of p-creosol (2-methoxy-4-methylphenol) to vanillin (4-hydroxy-3 methoxybenzaldehyde). To elucidate how different ligands enter and exit the secluded active site, Monte Carlo based simulations have been performed. One entry/exit path via the subunit interface and two additional exit paths have been identified for phenolic ligands, all leading to the si side of FAD. We argue that the entry/exit path is the most probable route for these ligands. A fourth path leading to the re side of FAD has been found for the co-ligands dioxygen and hydrogen peroxide. Based on binding energies and on the behaviour of ligands in these four paths, we propose a sequence of events for ligand and co-ligand migration during catalysis. We have also identified two residues, His466 and Tyr503, which could act as concierges of the active site for phenolic ligands, as well as two other residues, Tyr51 and Tyr408, which could act as a gateway to the re side of FAD for dioxygen. Most of the residues in the four paths are also present in VAO's closest relatives, eugenol oxidase and p-cresol methylhydroxylase. Key path residues show movements in our simulations that correspond well to conformations observed in crystal structures of these enzymes. Preservation of other path residues can be linked to the electron acceptor specificity and oligomerisation state of the three enzymes. This study is the first comprehensive overview of ligand and co-ligand migration in a member of the VAO/PCMH family, and provides a proof of concept for the use of an unbiased method to sample this process. PMID- 28985220 TI - Combinatorial treatment with topical NSAIDs and anti-VEGF for age-related macular degeneration, a meta-analysis. AB - Inflammation is a key pathogenic factor in age-related macular degeneration (AMD). However, the clinical importance of combining anti-VEGF agents and topical NSAIDs to reduce inflammation remains unclear. In this study, we systematically reviewed clinical trials comparing combined treatment versus anti-VEGF alone in AMD patients. We quantified treatment effects via meta-analysis. The pooled weighted mean difference (WMD, -0.91, 95%CI: -1.39 to -0.42, P = 0.0003) demonstrates that combined treatment may reduce required anti-VEGF injection number, probably by means of decreasing central retina thickness (CRT) (WMD = 22.9, 95% CI: -41.20 to -4.59, P = 0.01). The best corrected visual acuity (BCVA) did not change significantly between these two groups (WMD = - 0.01, 95%CI: -0.23 to 0.20, P = 0.90). Topical NSAIDs slightly increased the incidence of foreign body sensation (Odds Ratio [OR] = 2.63, 95%Cl: 1.06 to 6.52, P = 0.76). Combining topical NSAIDs and anti-VEGF agents may provide a new strategy for AMD treatment. PMID- 28985221 TI - Long-term outcomes of augmented unilateral recess-resect procedure in children with intermittent exotropia. AB - BACKGROUND: Initial overcorrection after exotropia surgery has been considered as a desirable result. Recently, there had been several studies that reported better surgical results of augmented bilateral lateral rectus muscle recession procedure over the conventional procedure. OBJECTIVES: To compare the long-term results of augmented unilateral lateral rectus recession-medial rectus resection procedure (RR) with the original surgery in exotropic children. DATA EXTRACTION: A retrospective cohort study was performed on a total of 121 children with exotropia who underwent RR from February 2005 to December 2012 and were followed up for at least 24 months. In 64 patients, RR was performed based on the original surgical table (original RR group). In 57 patients, the amount of medial rectus muscle resection was increased by 1 mm (augmented RR group). RESULTS: In the original RR group, 47 of 64 patients (73.4%) had a successful outcome, 13 patients (20.3%) had recurrence, and 4 patients (6.3%) had overcorrection at 2 years after surgery. In the augmented RR group, 45 of 57 patients (79.0%) were successful, 4 patients (7.0%) had recurrence and 8 patients (14.0%) had overcorrection at 2 years after surgery. The recurrence rate was significantly lower in the augmented RR group than the original RR group, whereas the overcorrection rate was not significantly different between two groups at 2 years after surgery (P = 0.036 and P = 0.153, respectively). The cumulative probability of recurrence was lower in the augmented group at 36 months after surgery (P = 0.046, log rank test). CONCLUSIONS: The long-term success rate of augmented RR in exotropic children was 79.0% and the recurrence rate was significantly lower than original RR with comparable overcorrection rates. Augmented RR can be considered as an alternative procedure in children with basic and convergence insufficiency type exotropia. PMID- 28985222 TI - Trace element contents in toenails are related to regular physical activity in older adults. AB - The aim was to assess the trace element contents in toenails of older adults and its association with regular physical activity. Cross-sectional multicentre study in Spain, collecting data from a random sample of 380 participants (54% female) aged 55-80 years (men) and 60-80 years (women) with no previously documented cardiovascular disease. Physical activity performed was measured using the Minnesota Leisure-time Physical Activity Questionnaire. The 25 most inactive and 25 most active individuals for each sex were selected for this study (final sample n = 100). Anthropometric measurements were performed and toenail samples collected for calcium (Ca), chromium (Cr), iron (Fe), cobalt (Co), nickel (Ni), zinc (Zn), selenium (Se) and mercury (Hg) analysis. Significant differences between sexes were reported in Ca concentrations, women having lower concentrations than men. No differences were reported in trace element contents between active and inactive men. Active women showed higher Ca, Cr, Fe, Co, and Zn and lower Hg contents than their inactive peers (all p<0.05). Inactive women showed lower Ca and Co levels (735.0 mg/kg and 4.5 MUg/kg, respectively) than inactive men (1170.0 mg/kg and 7.9 MUg/kg, respectively). Active women had lower Ca and higher levels of Cr (936.0 mg/kg and 1230.0 MUg/kg, respectively) than active men (1070.0 mg/kg and 522.0 MUg/kg, respectively). The present data added new information on the element contents in toenails of healthy Spanish older adults. The concentration of trace elements was similar in both sexes except for Ca which were lower in women. The trace element contents in women's toenails, but not in men, were markedly influenced by physical activity, with higher levels of Ca and Fe and lower Hg among active females. PMID- 28985223 TI - Heavy metals exposure levels and their correlation with different clinical forms of fetal growth restriction. AB - BACKGROUND: Prenatal heavy metals exposure has shown a negative impact on birth weight. However, their influence on different clinical forms of fetal smallness was never assessed. OBJECTIVES: To investigate whether there is a differential association between heavy metals exposure and fetal smallness subclassification into intrauterine growth restriction (IUGR) and small-for-gestational age (SGA). METHOD: In this prospective case-control study, we included 178 mother-infant pairs; 96 of appropriate for gestational age (AGA) and 82 of small fetuses diagnosed in third trimester. The small ones were further subclassified into IUGR, n = 49 and SGA, n = 33. Cadmium (Cd), mercury (Hg), lead (Pb), arsenic (As) and zinc (Zn) levels were measured in the maternal and cord serum, and in the placentas of the three groups. RESULTS: Maternal serum level of Cd (p<0.001) was higher in the small fetuses compared to AGA. Fetal serum level of Cd (p<0.001) was increased in the small fetuses compared to AGA. Fetal serum level of Hg (p<0.05) showed an increase in SGA compared to both IUGR and AGA. Fetal serum level of Zn was increased in the AGA (p < 0.001) compared to each of the small fetuses groups. Only differences in the levels between the small fetuses' subgroups were detected in the fetal serum levels of Cd and Hg. Fetal birth weight was negatively correlated with the fetal serum level of Cd (p < 0.001). No differences in the placental heavy metal levels were observed among the groups. CONCLUSION: Fetal serum levels of Cd showed differential correlation between small fetuses' clinical subclassification, which together with the increased Cd levels in both maternal and fetal serum of the small fetuses reinforce the negative influence of heavy metals on birth weight. These findings provide more opportunities to verify the role of heavy metals exposure in relation to small fetuses' subclassification. PMID- 28985225 TI - Disrupting assembly of the inner membrane complex blocks Plasmodium falciparum sexual stage development. AB - Transmission of malaria parasites relies on the formation of a specialized blood form called the gametocyte. Gametocytes of the human pathogen, Plasmodium falciparum, adopt a crescent shape. Their dramatic morphogenesis is driven by the assembly of a network of microtubules and an underpinning inner membrane complex (IMC). Using super-resolution optical and electron microscopies we define the ultrastructure of the IMC at different stages of gametocyte development. We characterize two new proteins of the gametocyte IMC, called PhIL1 and PIP1. Genetic disruption of PhIL1 or PIP1 ablates elongation and prevents formation of transmission-ready mature gametocytes. The maturation defect is accompanied by failure to form an enveloping IMC and a marked swelling of the digestive vacuole, suggesting PhIL1 and PIP1 are required for correct membrane trafficking. Using immunoprecipitation and mass spectrometry we reveal that PhIL1 interacts with known and new components of the gametocyte IMC. PMID- 28985224 TI - Caspase-8, association with Alzheimer's Disease and functional analysis of rare variants. AB - The accumulation of amyloid beta (Abeta) peptide (Amyloid cascade hypothesis), an APP protein cleavage product, is a leading hypothesis in the etiology of Alzheimer's disease (AD). In order to identify additional AD risk genes, we performed targeted sequencing and rare variant burden association study for nine candidate genes involved in the amyloid metabolism in 1886 AD cases and 1700 controls. We identified a significant variant burden association for the gene encoding caspase-8, CASP8 (p = 8.6x10-5). For two CASP8 variants, p.K148R and p.I298V, the association remained significant in a combined sample of 10,820 cases and 8,881 controls. For both variants we performed bioinformatics structural, expression and enzymatic activity studies and obtained evidence for loss of function effects. In addition to their role in amyloid processing, caspase-8 and its downstream effector caspase-3 are involved in synaptic plasticity, learning, memory and control of microglia pro-inflammatory activation and associated neurotoxicity, indicating additional mechanisms that might contribute to AD. As caspase inhibition has been proposed as a mechanism for AD treatment, our finding that AD-associated CASP8 variants reduce caspase function calls for caution and is an impetus for further studies on the role of caspases in AD and other neurodegenerative diseases. PMID- 28985226 TI - Scaling and maintenance of corneal thickness during aging. AB - Corneal thickness is tightly regulated by its boundary endothelial and epithelial layers. The regulated set-point of corneal thickness likely shows inter individual variations, changes by age, and response to stress. Using anterior segment-optical coherence tomography, we measure murine central corneal thickness and report on body size scaling of murine central corneal thickness during aging. For aged-matched mice, we find that corneal thickness depends on sex and strain. To shed mechanistic insights into these anatomical changes, we measure epithelial layer integrity and endothelial cell density during the life span of the mice using corneal fluorescein staining and in vivo confocal microscopy, respectively and compare their trends with that of the corneal thickness. Cornea thickness increases initially (1 month: 114.7 +/- 3.0 MUm, 6 months: 126.3 +/- 1.6 MUm), reaches a maximum (9 months: 129.3 +/- 4.4 MUm) and then reduces (12 months: 127 +/- 2.9 MUm, 13 months: 119.5 +/- 7.6 MUm, 14 months: 110.6 +/- 10.6 MUm), while the body size (weight) increases with age. We find that endothelial cell density reduces from 2 months old to 8 months old as the mice age and epithelial layer accumulates damages within this time frame. Finally, we compare murine corneal thickness with those of several other mammals including humans and show that corneal thickness has an allometric scaling with body size. Our results have relevance for organ size regulation, translational pharmacology, and veterinary medicine. PMID- 28985227 TI - Nanoparticle curcumin ameliorates experimental colitis via modulation of gut microbiota and induction of regulatory T cells. AB - BACKGROUND AND AIMS: Curcumin is a hydrophobic polyphenol derived from turmeric, a traditional Indian spice. Curcumin exhibits various biological functions, but its clinical application is limited due to its poor absorbability after oral administration. A newly developed nanoparticle curcumin shows improved absorbability in vivo. In this study, we examined the effects of nanoparticle curcumin (named Theracurmin) on experimental colitis in mice. METHODS: BALB/c mice were fed with 3% dextran sulfate sodium (DSS) in water. Mucosal cytokine expression and lymphocyte subpopulation were analyzed by real-time PCR and flow cytometry, respectively. The profile of the gut microbiota was analyzed by real time PCR. RESULTS: Treatment with nanoparticle curcumin significantly attenuated body weight loss, disease activity index, histological colitis score and significantly improved mucosal permeability. Immunoblot analysis showed that NF kappaB activation in colonic epithelial cells was significantly suppressed by treatment with nanoparticle curcumin. Mucosal mRNA expression of inflammatory mediators was significantly suppressed by treatment with nanoparticle curcumin. Treatment with nanoparticle curcumin increased the abundance of butyrate producing bacteria and fecal butyrate level. This was accompanied by increased expansion of CD4+ Foxp3+ regulatory T cells and CD103+ CD8alpha- regulatory dendritic cells in the colonic mucosa. CONCLUSIONS: Treatment with nanoparticle curcumin suppressed the development of DSS-induced colitis potentially via modulation of gut microbial structure. These responses were associated with induction of mucosal immune cells with regulatory properties. Nanoparticle curcumin is one of the promising candidates as a therapeutic option for the treatment of IBD. PMID- 28985228 TI - Effect of lifestyle coaching versus care coordination versus treatment as usual in people with severe mental illness and overweight: Two-years follow-up of the randomized CHANGE trial. AB - The objective of this trial was to assess the long-term effect of the CHANGE lifestyle coaching intervention for 428 people with abdominal obesity and schizophrenia spectrum disorders on cardiovascular risk. In this randomized, superiority, multi-center clinical trial, participants were randomized to 12 months of either lifestyle coaching plus care coordination (N = 138), care coordination alone, (N = 142) or treatment as usual (N = 148). There was no effect after 12 months, but we hypothesized that there might have been a delayed treatment effect. Our primary outcome at two-year follow-up was 10-year risk of cardiovascular disease standardized to 60 years of age. After two-years the mean 10-year cardiovascular-disease risk was 8.7% (95% confidence interval (CI) 7.6 9.9%) in the CHANGE group, 7.7% (95% CI 6.5-8.9%) in the care coordination group, and 8.9% (95% CI 6.9-9.2%) in the treatment as usual group (P = 0.24). Also, there were no intervention effects for any secondary or exploratory outcomes, including cardiorespiratory fitness, weight, physical activity, diet and smoking. No reported adverse events could be ascribed to the intervention. We conclude that there was neither any direct nor any long-term effect of individual lifestyle coaching or care coordination on cardiovascular risk factors in people with abdominal obesity and schizophrenia spectrum disorders. The trial was approved by the Ethics Committee of Capitol Region Copenhagen, Denmark (registration number: H-4-2012-051) and the Danish Data Protection Agency (registration number: 01689 RHP-2012-007). The trial was funded by the Mental Health Services of the Capital Region of Denmark, the Lundbeck Foundation, the Tryg Foundation, the Danish Ministry of Health, and the Daehnfeldts Foundation. PMID- 28985229 TI - A deep convolutional neural network-based automatic delineation strategy for multiple brain metastases stereotactic radiosurgery. AB - Accurate and automatic brain metastases target delineation is a key step for efficient and effective stereotactic radiosurgery (SRS) treatment planning. In this work, we developed a deep learning convolutional neural network (CNN) algorithm for segmenting brain metastases on contrast-enhanced T1-weighted magnetic resonance imaging (MRI) datasets. We integrated the CNN-based algorithm into an automatic brain metastases segmentation workflow and validated on both Multimodal Brain Tumor Image Segmentation challenge (BRATS) data and clinical patients' data. Validation on BRATS data yielded average DICE coefficients (DCs) of 0.75+/-0.07 in the tumor core and 0.81+/-0.04 in the enhancing tumor, which outperformed most techniques in the 2015 BRATS challenge. Segmentation results of patient cases showed an average of DCs 0.67+/-0.03 and achieved an area under the receiver operating characteristic curve of 0.98+/-0.01. The developed automatic segmentation strategy surpasses current benchmark levels and offers a promising tool for SRS treatment planning for multiple brain metastases. PMID- 28985231 TI - Inferring oscillatory modulation in neural spike trains. AB - Oscillations are observed at various frequency bands in continuous-valued neural recordings like the electroencephalogram (EEG) and local field potential (LFP) in bulk brain matter, and analysis of spike-field coherence reveals that spiking of single neurons often occurs at certain phases of the global oscillation. Oscillatory modulation has been examined in relation to continuous-valued oscillatory signals, and independently from the spike train alone, but behavior or stimulus triggered firing-rate modulation, spiking sparseness, presence of slow modulation not locked to stimuli and irregular oscillations with large variability in oscillatory periods, present challenges to searching for temporal structures present in the spike train. In order to study oscillatory modulation in real data collected under a variety of experimental conditions, we describe a flexible point-process framework we call the Latent Oscillatory Spike Train (LOST) model to decompose the instantaneous firing rate in biologically and behaviorally relevant factors: spiking refractoriness, event-locked firing rate non-stationarity, and trial-to-trial variability accounted for by baseline offset and a stochastic oscillatory modulation. We also extend the LOST model to accommodate changes in the modulatory structure over the duration of the experiment, and thereby discover trial-to-trial variability in the spike-field coherence of a rat primary motor cortical neuron to the LFP theta rhythm. Because LOST incorporates a latent stochastic auto-regressive term, LOST is able to detect oscillations when the firing rate is low, the modulation is weak, and when the modulating oscillation has a broad spectral peak. PMID- 28985230 TI - Biological nanoparticles carrying the Hmda-7 gene are effective in inhibiting pancreatic cancer in vitro and in vivo. AB - OBJECTIVES: Pancreatic cancer is one of the most common malignancies of the digestive system, and remains a clinical challenge. This study aimed to assess the effects of bovine serum albumin (BSA) nanoparticles carrying the hMDA-7 gene (BSA-NP-hMDA-7) in the treatment of pancreatic cancer. METHODS: BSA-NP-hMDA-7 was generated by nanotechnology and gene recombination technology. A total of 5 BXPC 3 or PANC-1 pancreatic cancer cell groups were examined, including Control, BSA NPs, Empty vector, hMDA-7 plasmid, and hMDA-7 BSA-NPs groups, respectively. Proliferation and apoptosis of cultured cells were assessed by the MTT method and flow-cytometry, respectively. In addition, pancreatic cancer models were established with both cell lines in nude mice, and the expression profiles of hMDA-7 and VEGF in cancer tissues were measured by Western blot and immunohistochemistry. RESULTS: BSA-NP-hMDA-7 nanoparticles were successfully generated, and significantly inhibited the proliferation of BXPC-3 and PANC-1 cells; in addition, apoptosis rates were higher in both cell lines after treatment with BSA-NP-hMDA-7 (P<0.05). Nude mouse xenograft studies indicated that treatment with BSA-NP-hMDA-7 nanoparticles resulted in decreased tumor size. Moreover, the hMDA-7 protein was found in tumor tissues after hMDA-7 gene transfection, while BSA-NP-hMDA-7 significantly suppressed VEGF expression in tumor tissues. Similar results were obtained for both BXPC-3 and PANC-1 xenograft models. CONCLUSION: BSA nanoparticles carrying the hMDA-7 gene effectively transfected BXPC-3 and PANC-1 pancreatic cancer cells, causing reduced cell proliferation and enhanced apoptosis in vitro. In mouse xenografts, BSA-NP-hMDA-7 treatment decreased tumor size and reduced VEGF expression. These findings indicated that BSA-NP-hMDA-7 might exert anticancer effects via VEGF suppression. PMID- 28985232 TI - Altered cropping pattern and cultural continuation with declined prosperity following abrupt and extreme arid event at ~4,200 yrs BP: Evidence from an Indus archaeological site Khirsara, Gujarat, western India. AB - Archaeological sites hold important clues to complex climate-human relationships of the past. Human settlements in the peripheral zone of Indus culture (Gujarat, western India) are of considerable importance in the assessment of past monsoon human-subsistence-culture relationships and their survival thresholds against climatic stress exerted by abrupt changes. During the mature phase of Harappan culture between ~4,600-3,900yrsBP, the ~4,100+/-100yrsBP time slice is widely recognized as one of the major, abrupt arid-events imprinted innumerous well dated palaeo records. However, the veracity of this dry event has not been established from any archaeological site representing the Indus (Harappan) culture, and issues concerning timing, changes in subsistence pattern, and the likely causes of eventual abandonment (collapse) continue to be debated. Here we show a significant change in crop-pattern (from barley-wheat based agriculture to 'drought-resistant' millet-based crops) at ~4,200 yrs BP, based on abundant macrobotanical remains and C isotopes of soil organic matter (delta13CSOM) in an archaeological site at Khirsara, in the Gujarat state of western India. The crop change appears to be intentional and was likely used as an adaptation measure in response to deteriorated monsoonal conditions. The ceramic and architectural remains of the site indicate that habitation survived and continued after the ~4,200yrsBP dry climatic phase, but with declined economic prosperity. Switching to millet-based crops initially helped inhabitants to avoid immediate collapse due to climatic stresses, but continued aridity and altered cropping pattern led to a decline in prosperity levels of inhabitants and eventual abandonment of the site at the end of the mature Harappan phase. PMID- 28985233 TI - Frequency of breast cancer with hereditary risk features in Spain: Analysis from GEICAM "El Alamo III" retrospective study. AB - PURPOSE: To determine the frequency of breast cancer (BC) patients with hereditary risk features in a wide retrospective cohort of patients in Spain. METHODS: a retrospective analysis was conducted from 10,638 BC patients diagnosed between 1998 and 2001 in the GEICAM registry "El Alamo III", dividing them into four groups according to modified ESMO and SEOM hereditary cancer risk criteria: Sporadic breast cancer group (R0); Individual risk group (IR); Familial risk group (FR); Individual and familial risk group (IFR) with both individual and familial risk criteria. RESULTS: 7,641 patients were evaluable. Of them, 2,252 patients (29.5%) had at least one hereditary risk criteria, being subclassified in: FR 1.105 (14.5%), IR 970 (12.7%), IFR 177 (2.3%). There was a higher frequency of newly diagnosed metastatic patients in the IR group (5.1% vs 3.2%, p = 0.02). In contrast, in RO were lower proportion of big tumors (> T2) (43.8% vs 47.4%, p = 0.023), nodal involvement (43.4% vs 48.1%, p = 0.004) and lower histological grades (20.9% G3 for the R0 vs 29.8%) when compared to patients with any risk criteria. CONCLUSIONS: Almost three out of ten BC patients have at least one hereditary risk cancer feature that would warrant further genetic counseling. Patients with hereditary cancer risk seems to be diagnosed with worse prognosis factors. PMID- 28985234 TI - Pathogenesis and sexual transmission of Spondweni and Zika viruses. AB - The Spondweni serogroup of viruses (Flaviviridae, Flavivirus) is comprised of Spondweni virus (SPONV) and Zika virus (ZIKV), which are mosquito-borne viruses capable of eliciting human disease. Numerous cases of ZIKV sexual transmission in humans have been documented following the emergence of the Asian genotype in the Americas. The African ZIKV genotype virus was previously implicated in the first reported case of ZIKV sexual transmission. Reports of SPONV infection in humans have been associated with non-specific febrile illness, but no association with sexual transmission has been reported. In order to assess the relative efficiency of sexual transmission of different ZIKV strains and the potential capacity of SPONV to be sexually transmitted, viral loads in the male reproductive tract and in seminal fluids were assessed in interferon alpha/beta and -gamma receptor deficient (AG129) mice. Male mice were inoculated subcutaneously with Asian genotype ZIKV strains PRVABC59 (Puerto Rico, 2015), FSS13025 (Cambodia, 2010), or P6-740 (Malaysia, 1966); African genotype ZIKV strain DakAr41524 (Senegal, 1984); or SPONV strain SAAr94 (South Africa, 1955). Infectious virus was detected in 60 72% of ejaculates collected from AG129 mice inoculated with ZIKV strains. In contrast, only 4% of ejaculates from SPONV-inoculated AG129 males were found to contain infectious virus, despite viral titers in the testes that were comparable to those of ZIKV-inoculated mice. Based on these results, future studies should be undertaken to assess the role of viral genetic determinants and host tropism that dictate the differential sexual transmission potential of ZIKV and SPONV. PMID- 28985235 TI - A Bayesian approach to modelling heterogeneous calcium responses in cell populations. AB - Calcium responses have been observed as spikes of the whole-cell calcium concentration in numerous cell types and are essential for translating extracellular stimuli into cellular responses. While there are several suggestions for how this encoding is achieved, we still lack a comprehensive theory. To achieve this goal it is necessary to reliably predict the temporal evolution of calcium spike sequences for a given stimulus. Here, we propose a modelling framework that allows us to quantitatively describe the timing of calcium spikes. Using a Bayesian approach, we show that Gaussian processes model calcium spike rates with high fidelity and perform better than standard tools such as peri-stimulus time histograms and kernel smoothing. We employ our modelling concept to analyse calcium spike sequences from dynamically-stimulated HEK293T cells. Under these conditions, different cells often experience diverse stimulus time courses, which is a situation likely to occur in vivo. This single cell variability and the concomitant small number of calcium spikes per cell pose a significant modelling challenge, but we demonstrate that Gaussian processes can successfully describe calcium spike rates in these circumstances. Our results therefore pave the way towards a statistical description of heterogeneous calcium oscillations in a dynamic environment. PMID- 28985236 TI - Discovery by organism based high-throughput screening of new multi-stage compounds affecting Schistosoma mansoni viability, egg formation and production. AB - Schistosomiasis, one of the most prevalent neglected parasitic diseases affecting humans and animals, is caused by the Platyhelminthes of the genus Schistosoma. Schistosomes are the only trematodes to have evolved sexual dimorphism and the constant pairing with a male is essential for the sexual maturation of the female. Pairing is required for the full development of the two major female organs, ovary and vitellarium that are involved in the production of different cell types such as oocytes and vitellocytes, which represent the core elements of the whole egg machinery. Sexually mature females can produce a large number of eggs each day. Due to the importance of egg production for both life cycle and pathogenesis, there is significant interest in the search for new strategies and compounds not only affecting parasite viability but also egg production. Here we use a recently developed high-throughput organism-based approach, based on ATP quantitation in the schistosomula larval stage of Schistosoma mansoni for the screening of a large compound library, and describe a pharmacophore-based drug selection approach and phenotypic analyses to identify novel multi-stage schistosomicidal compounds. Interestingly, worm pairs treated with seven of the eight compounds identified show a phenotype characterized by defects in eggshell assemblage within the ootype and egg formation with degenerated oocytes and vitelline cells engulfment in the uterus and/or oviduct. We describe promising new molecules that not only impair the schistosomula larval stage but also impact juvenile and adult worm viability and egg formation and production in vitro. PMID- 28985238 TI - The pain threshold of high-threshold mechanosensitive receptors subsequent to maximal eccentric exercise is a potential marker in the prediction of DOMS associated impairment. AB - BACKGROUND: Delayed-onset muscle soreness (DOMS) refers to dull pain and discomfort in people after participating in exercise, sport or recreational physical activities. The aim of this study was to detect underlying mechanical thresholds in an experimental model of DOMS. METHODS: Randomised study to detect mechanical pain thresholds in a randomised order following experimentally induced DOMS of the non-dominant arm in healthy participants. Main outcome was the detection of the pressure pain threshold (PPT), secondary thresholds included mechanical detection (MDT) and pain thresholds (MPT), pain intensity, pain perceptions and the maximum isometric voluntary force (MIVF). RESULTS: Twenty volunteers (9 female and 11 male, age 25.2 +/- 3.2 years, weight 70.5 +/- 10.8 kg, height 177.4 +/- 9.4 cm) participated in the study. DOMS reduced the PPT (at baseline 5.9 +/- 0.4 kg/cm2) by a maximum of 1.5 +/- 1.4 kg/cm2 (-24%) at 48 hours (p < 0.001). This correlated with the decrease in MIVF (r = -0.48, p = 0.033). Whereas subjective pain was an indicator of the early 48 hours, the PPT was still present after 72 hours (r = 0.48, p = 0.036). Other mechanical thresholds altered significantly due to DOMS, but did show no clinically or physiologically remarkable changes. CONCLUSIONS: Functional impairment following DOMS seems related to the increased excitability of high-threshold mechanosensitive nociceptors. The PPT was the most valid mechanical threshold to quantify the extent of dysfunction. Thus PPT rather than pain intensity should be considered a possible marker indicating the athletes' potential risk of injury. PMID- 28985240 TI - Doxycycline synergizes with doxorubicin to inhibit the proliferation of castration-resistant prostate cancer cells. AB - Castration-resistant prostate cancer (CRPC) is fatal and there is currently no effective clinical treatment. The antibiotic doxycycline has shown anti-cancer effect in several kinds of solid tumors including prostate cancer. In this study, a combination of doxycycline and doxorubicin was used to investigate the synergistic effect on CRPC cells. MTT assay was employed to determine the viability of cells in two-dimensional (2D) cultures. Apoptosis was determined by Annexin V/propidium iodide (PI) double staining assay. Cell cycle was analyzed by PI staining, and reverse transcription-PCR (RT-PCR) was used to determine the expressions of apoptosis-related genes at mRNA level. Western blot analysis was used to analyze the expressions of Bcl-2, Bax, and Poly (ADP-ribose) polymerase proteins. Cytotoxicity assay and morphological observation of PC3 cells in three dimensional (3D) cultures were used to determine the effect of combination treatment. Results showed that doxycycline combined with doxorubicin significantly inhibited PC3 cells in both 2D and 3D cultures, enhanced apoptosis, and increased the accumulation of cells in G2/M phase. RT-PCR showed down regulation of Bcl-2 and up-regulation of Bax mRNA after combination treatment. Meanwhile, western blot analysis showed that combination treatment resulted in down-regulation of Bcl-2 protein and up-regulation of Bax protein, and that PARP cleavage was obviously exhibited after combination treatment. Confocal imaging analysis indicated that doxorubicin penetrated deeply into the core of spheroids when combined with doxycycline. These data indicated that doxycycline in combination with doxorubicin had a synergistic effect on PC3 cells and may provide a potential novel strategy for the treatment of CRPC. PMID- 28985237 TI - Enterovirus 71 protease 2Apro and 3Cpro differentially inhibit the cellular endoplasmic reticulum-associated degradation (ERAD) pathway via distinct mechanisms, and enterovirus 71 hijacks ERAD component p97 to promote its replication. AB - Endoplasmic reticulum-associated degradation (ERAD) is an important function for cellular homeostasis. The mechanism of how picornavirus infection interferes with ERAD remains unclear. In this study, we demonstrated that enterovirus 71 (EV71) infection significantly inhibits cellular ERAD by targeting multiple key ERAD molecules with its proteases 2Apro and 3Cpro using different mechanisms. Ubc6e was identified as the key E2 ubiquitin-conjugating enzyme in EV71 disturbed ERAD. EV71 3Cpro cleaves Ubc6e at Q219G, Q260S, and Q273G. EV71 2Apro mainly inhibits the de novo synthesis of key ERAD molecules Herp and VIMP at the protein translational level. Herp differentially participates in the degradation of different glycosylated ERAD substrates alpha-1 antitrypsin Null Hong Kong (NHK) and the C-terminus of sonic hedgehog (SHH-C) via unknown mechanisms. p97 was identified as a host factor in EV71 replication; it redistributed and co-exists with the viral protein and other known replication-related molecules in EV71 induced replication organelles. Electron microscopy and multiple-color confocal assays also showed that EV71-induced membranous vesicles were closely associated with the endoplasmic reticulum (ER), and the ER membrane molecule RTN3 was redistributed to the viral replication complex during EV71 infection. Therefore, we propose that EV71 rearranges ER membranes and hijacks p97 from cellular ERAD to benefit its replication. These findings add to our understanding of how viruses disturb ERAD and provide potential anti-viral targets for EV71 infection. PMID- 28985241 TI - Short-Term High-Salt Diet Increases Corin Level to Regulate the Salt-Water Balance in Humans and Rodents. AB - BACKGROUND: Dietary sodium and potassium affect the fluctuation in blood pressure (BP) and renal function. Corin, with its enzymatic activity to convert pro-atrial natriuretic peptide (pro-ANP) to biologically active ANP, regulates BP, cardiac, and renal functions. We investigated whether corin expression responds to a high salt (HS) diet to regulate salt and water balance. METHODS: Forty-two volunteers followed 3 sequential diets for 7 days each: a low-salt (LS) diet (3.0 g/day NaCl), a HS diet (18.0 g/day NaCl), followed by an HS diet with K+ supplementation (HS + K+) (18.0 g/day NaCl and 4.5 g/day KCl). RESULTS: Corin level was higher with the HS diet than the LS and HS + K+ diets and was positively correlated with systolic BP (SBP) and 24-hour urinary Na+ and microalbumin (U-mALB) excretion. In rodents, serum and renal levels of corin were transiently increased with the HS diet and were decreased if the HS diet was continued for up to 7 days. HS loading increased SBP, 24-hour urinary Na+, U-mALB excretion, and the expression of proprotein convertase subtilisin/kexin-6 (PCSK6), a corin activator. Knockdown of PCSK6 or corin in high salt-treated M1 cortical collecting duct (M1-CCD) cells increased the expression of aquaporin 2 (AQP2) and beta-epithelial Na+ channel (beta-ENaC). CONCLUSIONS: Short-term HS may induce the PCSK6-corin-ANP-AQP2/beta-ENaC pathway in the kidney. Enhanced serum corin level in humans and rodents is positively correlated with HS-induced SBP and 24-hour urinary Na+ and U-mALB excretion, which suggests that corin is involved in the salt-water balance in response to HS intake. CLINICAL TRIALS REGISTRATION: Public Trials Registry Number NCT02915315. PMID- 28985243 TI - Conducting and reporting trials for older people. AB - Randomised controlled trials provide the most rigorous test of efficacy and effectiveness for interventions used in healthcare. They underpin much of clinical practice, yet older people are often excluded from studies, resulting in uncertainty about risks and benefits of new treatments. Encouraging inclusion of older people in randomised controlled trials and reporting of trial results in a rigorous manner is a key function of clinical geriatrics journals such as Age and Ageing. This article provides practical advice on how to report randomised controlled trials that are targeted at older people. Some of these issues are generic, but there are specific requirements which apply to most studies of older people. Recording and reporting basic characteristics of recruits in terms of physical function, cognition, comorbidity and/or frailty is vital to allow proper interpretation of the external validity of the trial. Adverse effects should include consideration of common geriatric problems including falls. Authors should follow the CONSORT reporting guidelines (CONsolidated Standards Of Reporting Trials) to enhance the transparency and quality of their manuscript. PMID- 28985242 TI - Development of an international undergraduate curriculum for delirium using a modified delphi process. AB - Background: delirium is a medical emergency affecting approximately 30% of hospitalised older patients. Recent work examining UK undergraduate medical curricula highlighted inconsistencies in the delivery of teaching on delirium. The aim of this project was to develop consensus agreement on a delirium curriculum for medical undergraduates. Methods: a modified Delphi process was used to determine consensus amongst experts in an iterative manner. Experts at the European Delirium Association Conference (London, 2015) were invited to participate. Participants were asked to consider: (i) What should be taught? (ii) How should teaching be delivered? (iii) Who should deliver the teaching? (iv) Where should the teaching be delivered? (v) When should the teaching be delivered? Delphi rounds continued until consensus on curriculum content (defined as 80% agreement) was achieved. Results: consensus was reached after three rounds. A recurrent theme was the need to involve patients, families and carers to help drive attitudinal change. The final curriculum, along with data pertaining to agreement with each curriculum item during the Delphi process, is presented. Conclusion: this Delphi process enabled an international group of experts from a broad range of specialties, to reach consensus agreement on the components of an undergraduate curriculum for delirium. The curriculum represents an important step in the development of delirium education within medical training. Despite competing demands of increasingly crowded undergraduate curricula, delirium, given its relevance to 21st century healthcare, must be prioritised. We call on Medical Schools to consider integrating this delirium curriculum into their degree programmes. PMID- 28985239 TI - Safety and immunogenicity of rVSVDeltaG-ZEBOV-GP Ebola vaccine in adults and children in Lambarene, Gabon: A phase I randomised trial. AB - BACKGROUND: The rVSVDeltaG-ZEBOV-GP vaccine prevented Ebola virus disease when used at 2 * 107 plaque-forming units (PFU) in a trial in Guinea. This study provides further safety and immunogenicity data. METHODS AND FINDINGS: A randomised, open-label phase I trial in Lambarene, Gabon, studied 5 single intramuscular vaccine doses of 3 * 103, 3 * 104, 3 * 105, 3 * 106, or 2 * 107 PFU in 115 adults and a dose of 2 * 107 PFU in 20 adolescents and 20 children. The primary objective was safety and tolerability 28 days post-injection. Immunogenicity, viraemia, and shedding post-vaccination were evaluated as secondary objectives. In adults, mild-to-moderate adverse events were frequent, but there were no serious or severe adverse events related to vaccination. Before vaccination, Zaire Ebola virus (ZEBOV)-glycoprotein (GP)-specific and ZEBOV antibodies were detected in 11% and 27% of adults, respectively. In adults, 74% 100% of individuals who received a dose 3 * 104, 3 * 105, 3 * 106, or 2 * 107 PFU had a >=4.0-fold increase in geometric mean titres (GMTs) of ZEBOV-GP-specific antibodies at day 28, reaching GMTs of 489 (95% CI: 264-908), 556 (95% CI: 280 1,101), 1,245 (95% CI: 899-1,724), and 1,503 (95% CI: 931-2,426), respectively. Twenty-two percent of adults had a >=4-fold increase of ZEBOV antibodies, with GMTs at day 28 of 1,015 (647-1,591), 1,887 (1,154-3,085), 1,445 (1,013-2,062), and 3,958 (2,249-6,967) for the same doses, respectively. These antibodies persisted up to day 180 for doses >=3 * 105 PFU. Adults with antibodies before vaccination had higher GMTs throughout. Neutralising antibodies were detected in more than 50% of participants at doses >=3 * 105 PFU. As in adults, no serious or severe adverse events related to vaccine occurred in adolescents or children. At day 2, vaccine RNA titres were higher for adolescents and children than adults. At day 7, 78% of adolescents and 35% of children had recombinant vesicular stomatitis virus RNA detectable in saliva. The vaccine induced high GMTs of ZEBOV GP-specific antibodies at day 28 in adolescents, 1,428 (95% CI: 1,025-1,989), and children, 1,620 (95% CI: 806-3,259), and in both groups antibody titres increased up to day 180. The absence of a control group, lack of stratification for baseline antibody status, and imbalances in male/female ratio are the main limitations of this study. CONCLUSIONS: Our data confirm the acceptable safety and immunogenicity profile of the 2 * 107 PFU dose in adults and support consideration of lower doses for paediatric populations and those who request boosting. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR201411000919191. PMID- 28985246 TI - Trajectory of social isolation following hip fracture: an analysis of the English Longitudinal Study of Ageing (ELSA) cohort. AB - Background: social isolation is defined as a lack of meaningful and sustained communication or interactions with social networks. There is limited understanding on the prevalence of social isolation and loneliness in people following hip fracture and no previous understanding of how this changes over time. Objective: to determine the prevalence and trajectory of social isolation and loneliness before a hip fracture, during the recovery phase and a minimum of 2 years post-hip fracture in an English population. Methods: data were from the English Longitudinal Study of Ageing (ELSA) cohort (2004/5-2014/15). The sample comprised of 215 participants who had sustained a hip fracture. Measures of social isolation and loneliness were analysed through multilevel modelling to determine their trajectories during three-time intervals (pre-fracture; interval at hip fracture and recovery; minimum 2 years post-fracture). The prevalence of social isolation and loneliness were determined pre- and post-fracture. Results: prevalence of social isolation was 19% post-hip fracture and loneliness 13% post hip fracture. There was no statistically significant change in social isolation pre-fracture compared to a minimum of 2 years post-fracture (P = 0.78). Similarly, there was no statistically significant change in loneliness pre fracture compared to a minimum of 2 years post-fracture (P = 0.12). Conclusion: this analysis has determined that whilst social isolation and loneliness do not change over time following hip fracture, these remain a significant problem for this population. Interventions are required to address these physical and psychological health needs. This is important as they may have short and longer term health benefits for people post-hip fracture. PMID- 28985244 TI - Menthol-Induced Cutaneous Vasodilation Is Preserved in Essential Hypertensive Men and Women. AB - BACKGROUND: Menthol is a selective transient receptor potential melastatin 8 (TRPM8) channel agonist that induces cutaneous vasodilation in young, normotensive men and women through nitric oxide synthase (NOS)-, endothelium derived hyperpolarizing factor (EDHF)-, and sensory nerve-mediated mechanisms. Microvascular dysfunction is present in essential hypertension and whether menthol induces vasodilation is men and women with essential hypertension is equivocal. METHODS: Four intradermal microdialysis fibers were placed in the forearm of 9 essential hypertensive and 10 age-matched normotensive control subjects. Sites were pretreated with lactated Ringer's (control), l-NAME (NOS inhibited), TEA (EDHF inhibited), and lidocaine (sensory nerve inhibited). The microdialysis fibers were then perfused with 7 increasing doses of menthol (0.1 500 mM). Red cell flux in response to menthol was measured with laser Doppler flowmetry. Data were normalized to mean arterial pressure and presented as a percentage of site-specific maximum vasodilation (%CVCmax). RESULTS: At the control site, menthol caused vasodilation in both the normotensive and hypertensive groups (menthol doses 100, 250, and 500 mM; all P < 0.05 compared to baseline). There were no differences between groups (P = 0.58, main effect). There was no effect of either NOS or sensory nerve inhibition on menthol-induced vasodilation in the normotensive group; however, menthol-induced vasodilation was attenuated with NOS and sensory nerve inhibition in the hypertensive group. EDHF inhibition attenuated menthol-induced vasodilation in both groups. CONCLUSIONS: Menthol-induced vasodilation has NO, EDHF, and sensory nerve components. Menthol induced cutaneous vasodilation is preserved in hypertensive subjects. However, the hypertensive subjects exhibited a loss of redundant vasodilator systems. PMID- 28985247 TI - Hypertension and Cardiovascular Risk Profile in a Middle-Income Setting: The HELISUR Study. AB - BACKGROUND: Hypertension is the leading risk factor responsible for premature death worldwide, but its burden has shifted to low- and middle-income countries. Therefore, we studied hypertension and cardiovascular risk in the population of Suriname, a middle-income country with a predominantly urban population of African and Asian ancestry. METHODS: A random sample of 1,800 noninstitutionalized men and women aged 18-70 years was selected to be interviewed at home and examined at the local hospital for cardiovascular risk factors, asymptomatic organ damage, and cardiovascular disease. RESULTS: The 1,157 participants examined (37% men) were mainly of self-defined Asian (43%) or African (39%) ancestry, mean age 43 years (SD 14). The majority of the population (71%) had hypertension or prehypertension, respectively, 40% and 31%. Furthermore, 72% was obese or overweight, while 63% had diabetes or prediabetes. Only 1% of the adult population had an optimal cardiovascular risk profile. Hypertension awareness, treatment, and control were respectively 68%, 56%, and 20%. In line with this, 22% of the adult population had asymptomatic organ damage, including increased arterial stiffness, left ventricular hypertrophy, microalbuminuria, or asymptomatic chronic kidney disease. CONCLUSIONS: In this first extensive cardiovascular assessment in the general population of this middle-income Caribbean country, high prevalence of hypertension with inadequate levels of treatment and control was predominant. The findings emphasize the need for collaborative effort from national and international bodies to prioritize the implementation of affordable and sustainable public health programs that combat the escalating hypertension and cardiovascular risk factor burden. PMID- 28985245 TI - Heart Rate Variability and Cognitive Function In Middle-Age Adults: The Coronary Artery Risk Development in Young Adults. AB - BACKGROUND: Low heart rate variability (HRV), a marker of cardiac autonomic dysfunction, has been associated with major risk factors of cognitive impairment. Yet, the direct association of HRV with cognitive function remains relatively unexplored, particularly in midlife. METHODS: In 2005, 2 measures of short-term HRV, the SD of normal-to-normal intervals (SDNN) and the root mean square of successive differences (RMSSD), were calculated for participants of the Coronary Artery Risk Development in Young Adults study, and then categorized into quartiles. Five years later, 3 cognitive tests were administered for verbal memory ("Rey Auditory-Verbal Learning Test", RAVLT, range 0-15), processing speed ("Digit Symbol Substitution Test", DSST, range 0-133), and executive function ("Stroop interference"). RESULTS: Two thousand one hundred and eighteen participants (57.7% female, 42.2% Black) with a mean baseline age of 45.3 years were included in this analysis. In demographic-adjusted models, compared to participants with quartile 1 SDNN (lowest quartile), participants in the upper quartiles of SDNN scored better on the DSST (quartile 4: beta = 1.83 points better, P = 0.03; and quartile 3: beta = 1.95 points better, P = 0.03) and on the stroop (quartile 3: beta = 1.19 points better, P < 0.05; and quartile2: beta = 1.44 points better, P = 0.02). After adjusting for behavioral and cardiovascular risk factors, higher quartile SDNN remained significantly associated with better stroop score (quartile 3: beta = 1.21 points better, P = 0.04; and quartile 2: beta = 1.72 points better, P < 0.01) but not with DSST. There was no association between quartile of RMSSD and cognitive function, from fully adjusted models. CONCLUSIONS: Our findings suggest that higher quartile SDDN is associated with better executive function in midlife, above, and beyond cardiovascular risk factors. PMID- 28985248 TI - New horizons in multimorbidity in older adults. AB - The concept of multimorbidity has attracted growing interest over recent years, and more latterly with the publication of specific guidelines on multimorbidity by the National Institute for Health and Care Excellence (NICE). Increasingly it is recognised that this is of particular relevance to practitioners caring for older adults, where multimorbidity may be more complex due to the overlap of physical and mental health disorders, frailty and polypharmacy. The overlap of frailty and multimorbidity in particular is likely to be due to the widespread health deficit accumulation, leading in some cases to functional impairment. The NICE guidelines identify 'target groups' who may benefit from a tailored approach to care that takes their multimorbidity into account, and make a number of research recommendations. Management includes a proactive individualised assessment and care plan, which improves quality of life by reducing treatment burden, adverse events, and unplanned or uncoordinated care. PMID- 28985250 TI - Interventions to prevent and reduce excessive alcohol consumption in older people: a systematic review and meta-analysis. AB - Background: harmful alcohol consumption is reported to be increasing in older people. To intervene and reduce associated risks, evidence currently available needs to be identified. Methods: two systematic reviews in older populations (55+ years): (1) Interventions to prevent or reduce excessive alcohol consumption; (2) Interventions as (1) also reporting cognitive and dementia outcomes. Comprehensive database searches from 2000 to November 2016 for studies in English, from OECD countries. Alcohol dependence treatment excluded. Data were synthesised narratively and using meta-analysis. Risk of bias was assessed using NICE methodology. Reviews are reported according to PRISMA. Results: thirteen studies were identified, but none with cognition or dementia outcomes. Three related to primary prevention; 10 targeted harmful or hazardous older drinkers. A complex range of interventions, intensity and delivery was found. There was an overall intervention effect for 3- and 6-month outcomes combined (8 studies; 3,591 participants; pooled standard mean difference (SMD) -0.18 (95% CI -0.28, 0.07) and 12 months (6 studies; 2,788 participants SMD -0.16 (95% CI -0.32, 0.01) but risk of bias for most studies was unclear with significant heterogeneity. Limited evidence (three studies) suggested more intensive interventions with personalised feedback, physician advice, educational materials, follow-up could be most effective. However, simple interventions including brief interventions, leaflets, alcohol assessments with advice to reduce drinking could also have a positive effect. Conclusions: alcohol interventions in older people may be effective but studies were at unclear or high risk of bias. Evidence gaps include primary prevention, cost-effectiveness, impact on cognitive and dementia outcomes. PMID- 28985251 TI - Reply to 'Seasonal ambient changes influence inpatient falls' Magota et al. PMID- 28985249 TI - Occupational social and mental stimulation and cognitive decline with advancing age. AB - Objective: this study investigates the role of social and mental occupational characteristics in cognitive decline after retirement. Methods: the study included 1,048 subjects aged >=65 years from the Three City cohort. Participants were evaluated at home at the initial visit and at 2-year intervals for a period of 12 years. The study includes detailed assessments of cognition, health and information about the subjects' main occupation. The four cognitive tests have been grouped into one latent factor. Three independent raters specialised in employment were asked to evaluate the level of social and intellectual stimulation for each occupation, which was then rated as low, medium and high. Results: after controlling for potential confounding factors, no association was found between higher levels of social stimulation at work and baseline cognition (medium score, P = 0.440; high score, P = 0.700) as compared with a low level. While cognitive trajectories were initially similar between high and medium levels of social stimulation compared with that of a low level, with advancing age this association diverged whereby more social stimulation during work years was related to accelerated cognitive decline that further grew in magnitude with older age. For mental stimulation, differences were only observed at baseline, with greater levels of mental stimulation during work years being associated with better cognitive performance (medium score, beta = 0.573, P = 0.015; and high score, beta = 0.510; P = 0.090) compared with a low level of mental stimulation. Conclusion: workers retiring from occupations characterised by high levels of social stimulation may be at risk of accelerated cognitive decline with advancing age. PMID- 28985252 TI - Age- and sex-based recovery curves to track functional outcomes in older adults with total knee arthroplasty. AB - Background: older adults with total knee arthroplasty (TKA) frequently undergo rehabilitation to address limited knee flexion range-of-motion, quadriceps weakness and gait speed limitations. This study aimed to develop age- and sex specific recovery curves of knee flexion range-of-motion, quadriceps strength and fast gait speed post-TKA. Methods: a population-based sample of 2,987 patients undergoing primary TKA participated, of whom 2015 (68%) were 65 years of age or older. At 4, 8 and 12 weeks post surgery, knee flexion range-of-motion, quadriceps strength and fast gait speed were quantified. Quantile regression was used to determine the percentiles of the knee and gait measures. Results: the various knee and gait measures improved nonlinearly over time, with substantial improvements observed in the 1st 8-10 weeks post surgery. Age-specific, sex specific recovery curves were developed to show the recovery patterns at multiple percentile levels. A web interface was created to facilitate easy computation of the percentile rank for a given outcome value. Conclusions: we have provided reference percentile values for knee flexion range-of-motion, quadriceps strength and gait speed recovery post-TKA. Such information may assist rehabilitation professionals in interpreting outcomes and quantifying deviations from the expected recovery pattern. PMID- 28985253 TI - Reply to 'Seasonal ambient changes influence inpatient falls' Magota et al. PMID- 28985254 TI - Spontaneous Iliopsoas tendon rupture: a rare cause of hip pain in an older person. PMID- 28985256 TI - Does current smoking predict future frailty? The English longitudinal study of ageing. AB - Background: smoking is the single most preventable cause of morbidity and mortality. The evidence on independent associations between smoking in later life and incident frailty is scarce. Objectives: to examine the effect of current smoking in older people on the risk of developing frailty, controlling for important confounders. Methods: we used data of 2,542 community-dwelling older people aged >=60 years in England. Participants were classified as current smokers or non-smokers. Frailty was defined using modified Fried criteria. Multivariable logistic regression models were used to examine risk of 4-year incident frailty in current smokers compared with non-smokers, adjusted for demographic, socioeconomic and health variables. Results: of 2,542 participants, 261 and 2,281 were current smokers and non-smokers, respectively. The current smokers were significantly frailer, younger, with lower BMI, less educated, less wealthy and lonelier compared with non-smokers at baseline. In multivariable logistic regression models adjusting for age and gender, current smokers were twice as likely to develop frailty compared with non-smokers (odds ratio (OR) = 2.07, 95% confidence interval (CI) = 1.39-3.39, P = 0.001). The association is attenuated largely by controlling for socioeconomic status. Smoking remains significantly associated with incident frailty in fully adjusted models including age, gender, socioeconomic status, alcohol use, cognitive function and loneliness (OR = 1.60, 95% CI = 1.02-2.51, P = 0.04). The relationship is however attenuated when taking account of non-response bias through multiple imputation. Conclusions: current smokers compared with non-smokers were significantly more likely to develop frailty over 4 years among community-dwelling older people. Given that smoking is a modifiable lifestyle factor, smoking cessation may potentially prevent or delay developing frailty, even in old age. PMID- 28985255 TI - Haloperidol versus placebo for delirium prevention in acutely hospitalised older at risk patients: a multi-centre double-blind randomised controlled clinical trial. AB - Background: because the few randomised placebo-controlled trials investigating the potential role for prophylactic haloperidol in delirium prevention have focused on specific surgical populations, we investigated its efficacy and safety in acutely hospitalised older patients. Methods: this multi-centre, double-blind, stratified, block randomised, placebo-controlled trial was conducted at six Dutch hospitals. Patients age >=70 years, acutely admitted through the emergency department for general medicine or surgical specialties and at risk for delirium were randomised (n = 245) to haloperidol or placebo 1 mg orally twice-daily (maximum of 14 doses) on top of standard nonpharmacological prevention strategies. The primary outcome was delirium incidence. Other endpoints included delirium severity and duration, drug safety and clinical outcomes. Results: intention-to-treat analysis included 242 participants (calculated sample size n = 390, statistical power of current sample 59%) allocated to haloperidol (n = 118) or placebo (n = 124). In the haloperidol and placebo group, delirium incidence was 19.5 versus 14.5% (OR 1.43, 95% CI 0.72 to 2.78); median (IQR) delirium duration 4 (2, 5) versus 3 (1, 6) days (P = 0.366); maximum DRS-R-98 score 16 (9.8, 19.5) versus 10 (5.5, 22.5) (P = 0.549; 53.7% missing data); hospital LOS 7 (4, 10.3) versus 7 (5, 11.8) days (P = 0.343); 3-month mortality 9.9 versus 12.5% (OR 0.77, 95% CI 0.34 to 1.75), respectively. No treatment-limiting side effects were noted. Conclusions: prophylactic low-dose oral haloperidol did not reduce delirium incidence in acutely hospitalised older patients. Therefore, prophylactic use of haloperidol in this population is not recommended. PMID- 28985258 TI - Interarm Systolic and Diastolic Blood Pressure Difference Is Diversely Associated With Cerebral Atherosclerosis in Noncardioembolic Stroke Patients. AB - BACKGROUND: Interarm systolic and diastolic blood pressure differences (IASBD, IADBD) are not infrequent in various populations. Cerebral atherosclerosis, including extracranial cerebral atherosclerosis (ECAS) and intracranial cerebral atherosclerosis (ICAS), is an important risk factor for stroke. In this study, we aimed to investigate the relationship of IASBD, IADBD with presence and burden of ICAS and ECAS. METHODS: This was a retrospective hospital-based cross-sectional study. In total, 1,063 consecutive noncardioembolic ischemic stroke patients, who were checked for bi-brachial blood pressures from ankle-brachial index and brain magnetic resonance angiographic images of cerebral arteries, were included. The IASBD and IADBD were defined as absolute value of the blood pressure difference in both arms. RESULTS: In all included patients, patients with IASBD >=10 and IADBD >=10 were noted in 9.4% (100/1,063) and 5.3% (56/1,063). The patients with IASBD >=10 mm Hg were more frequently burdened with ICAS (P = 0.001) and ECAS (P = 0.027) and patients with IADBD >=10 mm Hg were more frequently burdened with ICAS (P = 0.042) but not ECAS (P = 0.187). Multivariate analysis after adjusting gender, age, and a P value <0.1 in univariate analysis showed IASBD >=10 mm Hg was associated with the presence of both ECAS and ICAS [odds ratio (OR): 2.96, 95% confidence interval (CI): 1.65-5.31]. The IADBD >=10 mm Hg was related with presence of ICAS only (OR: 1.87, 95% CI: 1.05-3.37) but not with ECAS only (OR: 1.50, 95% CI: 0.73-3.06). CONCLUSIONS: Our study showed IASBD and IADBD were diversely associated with cerebral atherosclerosis. In noncardioembolic stroke patients with IASBD >=10 or IADBD >=10, the possibility of accompanying cerebral atherosclerosis should be considered. PMID- 28985257 TI - Potentially inappropriate medication among people with dementia in eight European countries. AB - Objectives: to evaluate the frequency of potentially inappropriate medication (PIM) prescription among older people with dementia (PwD) from eight countries participating in the European study 'RightTimePlaceCare', and to evaluate factors and adverse outcomes associated with PIM prescription. Methods: survey of 2,004 PwD including a baseline assessment and follow-up after 3 months. Interviewers gathered data on age, sex, prescription of medication, cognitive status, functional status, comorbidity, setting and admission to hospital, fall-related injuries and mortality in the time between baseline and follow-up. The European Union(7)-PIM list was used to evaluate PIM prescription. Multivariate regression analysis was used to investigate factors and adverse outcomes associated with PIM prescription. Results: overall, 60% of the participants had at least one PIM prescription and 26.4% at least two. The PIM therapeutic subgroups most frequently prescribed were psycholeptics (26% of all PIM prescriptions) and 'drugs for acid-related disorders' (21%). PwD who were 80 years and older, lived in institutional long-term care settings, had higher comorbidity and were more functionally impaired were at higher risk of being prescribed two PIM or more. The prescription of two or more PIM was associated with higher chance of suffering from at least one fall-related injury and at least one episode of hospitalisation in the time between baseline and follow-up. Conclusions: PIM use among PwD is frequent and is associated with institutional long-term care, age, advanced morbidity and functional impairment. It also appears to be associated with adverse outcomes. Special attention should be paid to psycholeptics and drugs for acid-related disorders. PMID- 28985259 TI - Effectiveness and safety of oral anticoagulants in older patients with atrial fibrillation: a systematic review and meta-regression analysis. AB - Background and objective: the study analysed the effectiveness and safety of warfarin use compared with warfarin non-use and non-vitamin K antagonist oral anticoagulants (NOACs) in atrial fibrillation (AF) patients aged >=65 years. Methods: after searching PubMed and the Cochrane Library, 26 studies were included, with 10 comparing warfarin with warfarin non-use and 16 comparing warfarin with NOACs, in older AF patients (>=65 years). Results: warfarin use was superior to no antithrombotic therapy [relative risk (RR) 0.59, 95% confidence interval (CI) 0.51-0.76, I2 = 12.3%, n = 8] and aspirin (RR 0.44, 95% CI 0.24 0.64, I2 = 0.0%, n = 5) for stroke/thromboembolism (TE) prevention. Warfarin use was associated with a non-significant increase in risk of major bleeding compared with no antithrombotic therapy (RR 1.26, 95% CI 0.99-1.52, I2 = 0.0%, n = 7) and aspirin (RR 1.20, 95% CI 0.91-1.50, I2 = 0.0%, n = 5). NOACs were superior to warfarin for stroke/TE prevention [hazard ratio (HR) 0.81, 95% CI 0.73-0.89, I2 = 56.6%, n = 9], and also were associated with reduced risk of major bleeding compared to warfarin (HR 0.87, 0.77-0.97, I2 = 86.1%, n = 9). Conclusions: warfarin use was superior to warfarin non-use, aspirin and no antithrombotic therapy in reducing the risk of stroke/TE in older AF patients, but with a possible increase in major bleeding. NOACs were superior to warfarin for stroke/TE prevention, with reduced risk of major bleeding. PMID- 28985261 TI - Lessons learned from a case of Candida Discitis. PMID- 28985260 TI - Validation of the 6-Item Cognitive Impairment Test and the 4AT test for combined delirium and dementia screening in older Emergency Department attendees. AB - Background: screening for cognitive impairment in Emergency Department (ED) requires short, reliable tools. Objective: to validate the 4AT and 6-Item Cognitive Impairment Test (6-CIT) for ED dementia and delirium screening. Design: diagnostic accuracy study. Setting/subjects: attendees aged >=70 years in a tertiary care hospital's ED. Methods: trained researchers assessed participants using the Standardised Mini Mental State Examination, Delirium Rating Scale Revised 98 and Informant Questionnaire on Cognitive Decline in the Elderly, informing ultimate expert diagnosis using Diagnostic and Statistical Manual of Mental Disorders (DSM-V) criteria for dementia and delirium (reference standards). Another researcher blindly screened each participant, within 3 h, using index tests 4AT and 6-CIT. Result: of 419 participants (median age 77 years), 15.2% had delirium and 21.5% had dementia. For delirium detection, 4AT had positive predictive value (PPV) 0.68 (95% confidence intervals: 0.58-0.79) and negative predictive value (NPV) 0.99 (0.97-1.00). At a pre-specified 9/10 cut off (9 is normal), 6-CIT had PPV 0.35 (0.27-0.44) and NPV 0.98 (0.95-0.99). Importantly, 52% of participants had no family present. A novel algorithm for scoring 4AT item 4 where collateral history is unavailable (score 4 if items 2-3 score >=1; score 0 if items 1-3 score is 0) proved reliable; PPV 0.65 (0.54-0.76) and NPV 0.99 (0.97-1.00). For dementia detection, 4AT had PPV 0.39 (0.32-0.46) and NPV 0.94 (0.89-0.96); 6-CIT had PPV 0.46 (0.37-0.55) and NPV 0.94 (0.90 0.97). Conclusion: 6-CIT and 4AT accurately exclude delirium and dementia in older ED attendees. 6-CIT does not require collateral history but has lower PPV for delirium. PMID- 28985262 TI - Evaluating physical activity in dementia: a systematic review of outcomes to inform the development of a core outcome set. AB - Background: physical activity is recommended for people living with dementia, but evidence for the positive effects of physical activity is limited by the use of heterogeneous outcomes and measurement tools. This systematic literature review aimed to summarise previously reported outcomes and identify the measurement tools used most frequently in physical activity interventions for people with dementia. Methods: literature searches were conducted in April 2015, on Delphis and Medline. Qualitative, quantitative and mixed methods studies reporting on any type of physical activity, in any setting, across types of dementia, stages of disease progression and published from 2005 onwards were included. A content analysis approach was used to report on the frequency of reported outcomes and measurement tools. Results: the 130 included studies reported on 133 different outcome domains and 267 different measurement tools. 'Functional abilities and independence' (n = 69), 'Global cognitive function' (n = 65), 'Balance' (n = 43), 'Global behavioural symptoms of dementia' (n = 42) and 'Health-related quality of life' (n = 40) were the most frequently reported outcome domains. 'Enjoyment' was the outcome most frequently sought by patients and carers. Conclusion: the need for the development and implementation of a Core Outcome Set has been reinforced. Ahead of the completion of the Core Outcome Set, researchers and clinicians are advised to measure the impact of physical activity interventions on these frequently reported outcome domains. PMID- 28985263 TI - The effect of perindopril on postural instability in older people with a history of falls-a randomised controlled trial. AB - Design: double-blind, parallel group, placebo-controlled randomised trial. Methods: we recruited people aged >65 years with at least one fall in the previous year. Participants received 4 mg perindopril or placebo daily for 15 weeks. The primary outcome was the between-group difference in force-plate measured anteroposterior (AP) sway at 15 weeks. Secondary outcomes included other measures of postural sway, limits of stability during maximal forward, right and left leaning, blood pressure, muscle strength, 6-min walk distance and falls. The primary outcome was assessed using two-way ANOVA, adjusted for baseline factors. Results: we randomised 80 participants. Mean age was 78.0 (SD 7.4) years; 60 (75%) were female. About 77/80 (96%) completed the trial. At 15 weeks there were no significant between-group differences in AP sway with eyes open (mean difference 0 mm, 95% CI -8 to 7 mm, P = 0.91) or eyes closed (mean difference 2 mm, 95% CI -7 to 12 mm, P = 0.59); no differences in other measures of postural stability, muscle strength or function. About 16/40 (42%) of patients in each group had orthostatic hypotension at follow-up. The median number (IQR) of falls was 1 (0,4) in the perindopril versus 1 (0,2) in the placebo group (P = 0.24). Conclusions: perindopril did not improve postural sway in older people at risk of falls. Clinical Trials Registration: ISRCTN58995463. PMID- 28985266 TI - Enabling Research in Care Homes. PMID- 28985265 TI - Health-related quality of life in older patients with acute coronary syndrome randomised to an invasive or conservative strategy. The After Eighty randomised controlled trial. AB - Objective: in the After Eighty study (ClinicalTrials.gov.number, NCT01255540), patients aged 80 years or more, with non-ST-elevation myocardial infarction (NSTEMI), and unstable angina pectoris (UAP), were randomised to either an invasive or conservative management approach. We sought to compare the effects of these management strategies on health related quality of life (HRQOL) after 1 year. Methods: the After Eighty study was a prospective randomised controlled multicenter trial. In total, 457 patients aged 80 or over, with NSTEMI or UAP, were randomised to either an invasive strategy (n = 229, mean age: 84.7 years), involving early coronary angiography, with immediate evaluation for percutaneous coronary intervention, coronary artery bypass graft, optimal medical therapy, or to a conservative strategy (n = 228, mean age: 84.9 years). The Short Form 36 health survey (SF-36) was used to assess HRQOL at baseline, and at the 1-year follow-up. Results: baseline SF-36 completion was achieved for 208 and 216 patients in the invasive and conservative groups, respectively. A total of 137 in the invasive group and 136 patients in the conservative group completed the SF-36 form at follow-up. When comparing the changes from follow-up to baseline (delta) no significant changes in quality-of-life scores were observed between the two strategies in any of the domains, expect for a small but statistically significant difference in bodily pain. This difference in only one of the SF-36 subscales may not necessarily be clinically significant. Conclusion: from baseline to the 1 year follow-up, only minor differences in change of HRQOL as measured by SF-36 were seen by comparing an invasive and conservative strategy. ClinicalTrials.gov identifier: NCT01255540. PMID- 28985264 TI - Comparative transcriptomics of cyprinid minnows and carp in a common wild setting: a resource for ecological genomics in freshwater communities. AB - Comparative transcriptomics can now be conducted on organisms in natural settings, which has greatly enhanced understanding of genome-environment interactions. Here, we demonstrate the utility and potential pitfalls of comparative transcriptomics of wild organisms, with an example from three cyprinid fish species (Teleostei:Cypriniformes). We present extensively filtered and annotated transcriptome assemblies that provide a valuable resource for studies of genome evolution (e.g. polyploidy), ecological and morphological diversification, speciation, and shared and unique responses to environmental variation in cyprinid fishes. Our results and analyses address the following points: (i) 'essential developmental genes' are shown to be ubiquitously expressed in a diverse suite of tissues across later ontogenetic stages (i.e. juveniles and adults), making these genes are useful for assessing the quality of transcriptome assemblies, (ii) the influence of microbiomes and other exogenous DNA, (iii) potentially novel, species-specific genes, and (iv) genomic rearrangements (e.g. whole genome duplication). The data we present provide a resource for future comparative work in cypriniform fishes and other taxa across a variety of sub-disciplines, including stress response, morphological diversification, community ecology, ecotoxicology, and climate change. PMID- 28985267 TI - Effect of Exercise on Arterial Stiffness: Is There a Ceiling Effect? AB - BACKGROUND: Whether arterial stiffness (AS) can be improved by regular exercise in healthy individuals remains equivocal according to cross-sectional and longitudinal studies assessing arterial properties at discrete time points. The purpose of the present study was to pinpoint the time course of training-induced adaptations in central AS. METHODS: Aorta characteristic impedance (Zc) and carotid distensibility (CD) were determined with ultrasonography prior to (week 0) and across 8 weeks (weeks 2, 4, and 8) of supervised endurance training (ET) (3 * 60 minutes cycle ergometry sessions per week), in 9 previously untrained healthy normotensive adults (27 +/- 4 years) with no history of cardiovascular disease. Exercise capacity was assessed by maximal oxygen consumption (VO2max) elicited by incremental ergometry. RESULTS: VO2max increased throughout the ET intervention (+12% from week 0 to week 8, P < 0.001, P for linear trend <0.001). Systolic blood pressure rose with ET (+7% from week 0 to week 8, P = 0.019, P for linear trend <0.001). Aorta Zc augmented from week 0 to week 8 of ET in all individuals (+38%, P = 0.003, P for linear trend = 0.002). CD did not significantly differ among time points (P = 0.196) although a linear decreasing trend was detected (P = 0.016). CONCLUSIONS: Central AS augments during a conventional ET intervention that effectively enhances aerobic exercise capacity in young individuals. This suggests that normal, healthy elastic arteries are not amendable to improvement unless impairment is present. PMID- 28985269 TI - Impact of the National Essential Public Health Services Policy on Hypertension Control in China. AB - BACKGROUND: Hypertension remains a severe challenge to population health worldwide. This study assessed the impact of a nationwide program in China Essential Public Health Services (EPHS) on improvement of hypertension treatment and control. METHODS: A cohort of hypertensive patients was identified from the 2011-2013 China Health and Retirement Longitudinal Study. Hypertension was defined based on: (i) an average systolic blood pressure of >=140 mm Hg, and/or an average diastolic blood pressure of >=90 mm Hg; and/or (ii) currently taking antihypertensive medications. Outcomes assessed included the rate of hypertension control, medication use, and blood pressure monitoring at a doctor's office. The key independent variable was defined as whether one received services from the EPHS-covered physical examination by 2013. Probit regression models with a difference-in-difference approach were performed for each of the 3 outcomes. Data were analyzed in 2017. RESULTS: Among the 4,958 hypertensive patients, 404 (8.1%) received the EPHS-covered service by 2013. Coverage by the EPHS program was associated with an increase of 7.9% in hypertension control rate (SE = 2.9%, P = 0.020), an increase of 10.3% in the rate of medication use (SE = 2.5%, P < 0.001), and an increase of 10.5% in the rate of blood pressure monitoring (SE = 2.5%, P < 0.001). Results also showed that the EPHS program helped mitigate the geographic disparities in access to health services such as blood pressure monitoring. CONCLUSIONS: The National EPHS program improved the treatment and control among hypertension patients. Expanding its program reach could further benefit the cardiovascular health of the population. PMID- 28985268 TI - Clinical Outcomes by Race and Ethnicity in the Systolic Blood Pressure Intervention Trial (SPRINT): A Randomized Clinical Trial. AB - BACKGROUND: The Systolic Blood Pressure Intervention Trial (SPRINT) showed that targeting a systolic blood pressure (SBP) of <= 120 mm Hg (intensive treatment) reduced cardiovascular disease (CVD) events compared to SBP of <= 140 mm Hg (standard treatment); however, it is unclear if this effect is similar in all racial/ethnic groups. METHODS: We analyzed SPRINT data within non-Hispanic White (NHW), non-Hispanic Black (NHB), and Hispanic subgroups to address this question. High-risk nondiabetic hypertensive patients (N = 9,361; 30% NHB; 11% Hispanic) 50 years and older were randomly assigned to intensive or standard treatment. Primary outcome was a composite of the first occurrence of a myocardial infarction, acute coronary syndrome, stroke, decompensated heart failure, or CVD death. RESULTS: Average postbaseline SBP was similar among NHW, NHB, and Hispanics in both treatment arms. Hazard ratios (HRs) (95% confidence interval) (intensive vs. standard treatment groups) for primary outcome were 0.70 (0.57 0.86), 0.71 (0.51-0.98), 0.62 (0.33-1.15) (interaction P value = 0.85) in NHW, NHB, and Hispanics. CVD mortality HRs were 0.49 (0.29-0.81), 0.77 (0.37-1.57), and 0.17 (0.01-1.08). All-cause mortality HRs were 0.61 (0.47-0.80), 0.92 (0.63 1.35), and 1.58 (0.73-3.62), respectively. A test for differences among racial/ethnic groups in the effect of treatment assignment on all-cause mortality was not significant (Hommel-adjusted P value = 0.062) after adjustment for multiple comparisons. CONCLUSION: Targeting a SBP goal of <= 120 mm Hg compared to <= 140 mm Hg led to similar SBP control and was associated with similar benefits and risks among all racial ethnic groups, though NHBs required an average of ~0.3 more medications. CLINICAL TRIALS REGISTRATION: Trial Number NCT01206062, ClinicalTrials.gov Identifier at https://clinicaltrials.gov/ct2/show/NCT01206062. PMID- 28985270 TI - Dietary Sodium Modifies Serum Uric Acid Concentrations in Humans. AB - BACKGROUND: Subjects with hypertension are frequently obese or insulin resistant, both conditions in which hyperuricemia is common. Obese and insulin-resistant subjects are also known to have blood pressure that is more sensitive to changes in dietary sodium intake. Whether hyperuricemia is a resulting consequence, moderating or contributing factor to the development of hypertension has not been fully evaluated and very few studies have reported interactions between sodium intake and serum uric acid. METHODS: We performed further analysis of our randomized controlled clinical trials (Australian New Zealand Clinical Trials Registry #12609000161224 and #12609000292279) designed to assess the effects of modifying sodium intake on concentrations of serum markers, including uric acid. Uric acid and other variables (including blood pressure, renin, and aldosterone) were measured at baseline and 4 weeks following the commencement of low (60 mmol/day), moderate (150 mmol/day), and high (200-250 mmol/day) dietary sodium intake. RESULTS: The median aldosterone-to-renin ratio was 1.90 [pg/ml]/[pg/ml] (range 0.10-11.04). Serum uric acid fell significantly in both the moderate and high interventions compared to the low sodium intervention. This pattern of response occurred when all subjects were analyzed, and when normotensive or hypertensive subjects were analyzed alone. CONCLUSIONS: Although previously reported in hypertensive subjects, these data provide evidence in normotensive subjects of an interaction between dietary sodium intake and serum uric acid. As this interaction is present in the absence of hypertension, it is possible it could play a role in hypertension development, and will need to be considered in future trials of dietary sodium intake. CLINICAL TRIALS REGISTRATION: The trials were registered with the Australian and New Zealand Clinical Trials Registry as ACTRN12609000161224 and ACTRN1260. PMID- 28985271 TI - ECG Voltage in Relation to Peripheral and Central Ambulatory Blood Pressure. AB - BACKGROUND: The heart ejects in the central elastic arteries. No previous study in workers described the diurnal profile of central blood pressure (BP) or addressed the question whether electrocardiogram (ECG) indexes are more closely associated with central than peripheral BP. METHODS: In 177 men (mean age, 29.1 years), we compared the associations of ECG indexes with brachial and central ambulatory BP, measured over 24 hours by the validated oscillometric Mobil-O Graph 24h PWA monitor. RESULTS: From wakefulness to sleep, as documented by diaries, systolic/diastolic BP decreased by 11.7/13.1 mm Hg peripherally and 9.3/13.6 mm Hg centrally, whereas central pulse pressure (PP) increased by 4.3 mm Hg (P < 0.0001). Over 24 hours and the awake and asleep periods, the peripheral minus-central differences in systolic/diastolic BPs averaged 11.8/-1.6, 12.7/ 1.8, and 10.3/-1.2 mm Hg, respectively (P < 0.0001). Cornell voltage and index averaged 1.18 mV and 114.8 mV.ms. Per 1-SD increment in systolic/diastolic BP, the Cornell voltages were 0.104/0.086 mV and 0.082/0.105 mV higher in relation to brachial 24-hour and asleep BP and 0.088/0.90 mV and 0.087/0.107 mV higher in relation to central BP. The corresponding estimates for the Cornell indexes were 9.6/8.6 and 8.2/10.5 mV.ms peripherally and 8.6/8.9 and 8.8/10.7 mV.ms centrally. The regression slopes (P >= 0.067) and correlation coefficients (P >= 0.088) were similar for brachial and central BP. Associations of ECG measurements with awake BP and PP were not significant. CONCLUSIONS: Peripheral and central BPs run in parallel throughout the day and are similarly associated with the Cornell voltage and index. PMID- 28985272 TI - User-Friendly HPLC Method Development and Validation for Determination of Enalapril Maleate and Its Impurities in Enalapril Tablets. AB - The official method for the determination of Enalapril Maleate and its related substances in European Pharmacopoeia (EP) is a gradient liquid chromatographic method. The method used styrene-divinylbenzene copolymer column, mobile phase buffer pH 6.8 and column oven temperature 70 degrees C. In this method, the separation between main component Enalapril and Ph. Eur. Imp-A was not completed hence the achieving system suitability requirement is a tough task and it requires quite often adjustment in chromatographic parameters. Moreover, column oven temperature 70 degrees C is not user friendly to HPLC instruments and users. In this study, several changes were introduced to the method in order to improve the separation, peak shapes and to overcome the column oven temperature. A new user-friendly stability-indicating RP-HPLC method was developed for Enalapril related substances analysis. The developed method uses a ZORBAX Eclipse XDB-C18 column with column oven temperature at 55 degrees C and mobile phase containing acetonitrile and a phosphate buffer at pH 3.0. The method is capable of separating all the known impurities with resolution more than 3.5, which is much better than that obtained with the existing monograph methods. The optimized method was validated and demonstrated to have acceptable specificity, sensitivity, linearity, accuracy, precision, robustness, solution stability and equivalency to the EP method. The developed method proved to be applicable to a wide number of C18 reversed-phase columns. In addition, the Enalapril assay method also presented with 20 min run time. PMID- 28985273 TI - Homocysteine and Nighttime Blood Pressure Dipping-Is There a Connection? PMID- 28985274 TI - A Sensitive and Rapid LC-MS-MS Method for Simultaneous Determination of Propafenone and Its Active Metabolite 5-Hydroxypropafenone in Human Plasma and Its Application in a Pharmacokinetic Study. AB - A simple and rapid high-performance liquid chromatography tandem mass spectrometry method for the determination of propafenone (PPF) and its active metabolite 5-hydroxypropafenone (5-OHP) in human plasma was developed and validated. This new method was linear and allowed simultaneous quantification of PPF and 5-OHP at a lower level of 0.5 ng/mL. The aliquot of 200 MUL plasma sample was simply treated with 4-fold methanol to deproteinize the plasma. The chromatographic separation was achieved on a Hedera ODS-2C18 analytical column with the mobile phase of methanol and 5 mM ammonium acetate solution containing 0.2% formic acid (pH 3.2) (68:32, v/v) at a flow rate of 0.4 mL/min. Quantitation of the analytes was achieved by multiple reaction monitoring under positive ionization mode. The method was successfully applied to a pharmacokinetic study of PPF and 5-OHP in healthy Chinese volunteers. After oral administration of a single dose of 425 mg PPF hydrochloride sustained-release capsule, the maximum peak plasma concentration (Cmax) of PPF was 210.9 +/- 141.9 ng/mL with a Tmax of 6 +/- 1 h, the Cmax of 5-OHP was 129.6 +/- 65.4 ng/mL with a Tmax of 7 +/- 2 h. The area under plasma concentration-time curve (AUC0-36) of PPF was 1610 +/- 1309 ng.h/mL with a t1/2 of 4.6 +/- 1.1 h, the AUC0-36 of 5-OHP was 1446 +/- 754 ng.h/mL with a t1/2 of 7.6 +/- 1.6 h. PMID- 28985275 TI - Race, Vigilant Coping Strategy, and Hypertension in an Integrated Community. AB - BACKGROUND: Vigilant coping refers to individuals who, potentially as a result of experiencing discrimination in the past, proactively prepare for the possibility that they will be discriminated against or mistreated because of their race. The extent to which vigilant coping is linked with hypertension, a highly prevalent condition with well-documented racial/ethnic disparities, remains largely unknown. METHODS: We performed a cross-sectional analysis of data from the Exploring Health Disparities in Integrated Communities (EHDIC) study-Southwest Baltimore (n = 715). We used a series of multivariate logistic regression models to evaluate vigilance as a potential mediator or moderator of the association between race, discrimination, and hypertension within the context of a racially integrated community. RESULTS: There was no difference in prevalence of hypertension between African-Americans and Whites in this sample (66.8 vs. 66.2; P = 0.86). A higher proportion of African-Americans reported discrimination (41.1 vs. 22.9; P < 0.0001) and vigilance (67.3 vs. 46.9; P < 0.0001) compared to Whites; however, neither measure was associated with hypertension. In stratified analyses, bothersome discrimination alongside vigilant coping was associated with higher odds of hypertension among African-Americans and lower odds among Whites. CONCLUSIONS: Overall, prevalence of hypertension was high and there were no racial differences in this racially integrated community. Discrimination, vigilance, and hypertension were differently associated among African-Americans and Whites. Studying lived experiences in integrated communities may illuminate how structural inequalities impact the health of African-Americans more broadly. Further, raising awareness of social factors as they relate to hypertension may help to inform clinical management of low-income patients. PMID- 28985276 TI - Mortality and Macrovascular Risk in Elderly With Hypertension and Diabetes: Effect of Intensive Drug Therapy. AB - BACKGROUND: This study identifies the effect of intensive drug therapy (IDT) in individuals age 65+ with diabetes (type 2 diabetes mellitus (T2D)) and hypertension on all-cause death, congestive heart failure (CHF), hospitalization for myocardial infarction (MI), and stroke or transient ischemic attack (TIA). METHODS: Individuals from the Medicare 5% dataset with hypertension and T2D undergoing IDT for these conditions were propensity score matched to a nonintensive drug-therapy group. Hazard ratios (HRs) were obtained using the Cox proportional hazard model. RESULTS: IDT was associated with increased risk of CHF (HR 2.32; 95% confidence interval (CI) 2.32-2.38), MI (HR 4.27; 95% CI 4.05 4.52), and stroke or TIA (HR 1.80; 95% CI 1.70-1.89) but decreased risk of death (HR 0.95; 95% CI 0.93-0.97). Risk for CHF (HR 0.73; 95% CI 0.71-0.73), MI (HR 0.64; 95% CI 0.62-0.67), stroke or TIA (HR 0.82; 95% CI 0.78-0.86), and death (HR 0.29; 95% CI 0.28-0.29) was decreased by adherence to diabetes management guidelines. CONCLUSIONS: Use of IDT in a high-risk population delays death but not severe macrovascular outcomes. Protective effects of IDT in high-risk patients likely outweigh polypharmacy-related health concerns. PMID- 28985277 TI - Arterial Stiffness, the Metabolic Syndrome, and the Brain. PMID- 28985279 TI - Are All "Arterial Stiffening" Parameters Equal or Are Some More Equal Than Others? PMID- 28985278 TI - Postexercise Hypotension After Aquatic Exercise in Older Women With Hypertension: A Randomized Crossover Clinical Trial. AB - BACKGROUND: Hypertension can be prevented and modified with lifestyle interventions that include regular exercise. Aquatic exercise is widely recommended for older adults for a variety of health benefits, but few studies have assessed the immediate ambulatory blood pressure (BP) response to aquatic exercise, a response termed postexercise hypotension (PEH). Thus, we assessed PEH after a session of aquatic exercise in physically active, older women with hypertension. METHODS: Twenty-four women 70.0 +/- 3.9 years with a resting systolic (SBP)/diastolic (DBP) BP of 124.0/72.3 mm Hg and body mass index of 29.8 +/- 4.1 kg/m2 were randomly assigned to participate in a 45-minute session of moderate intensity, water-based exercise (WATER) and a 45-minute land control session (CONTROL). All experimental sessions started at 9 am sharply with 7 days between them. Subjects left the experiments wearing an ambulatory BP monitor for the next 21 hours. RESULTS: SBP was lower by 5.1 +/- 1.0 mm Hg after WATER than CONTROL over 21 hours (P < 0.001), over awake hours by 5.7 +/- 1.1 mm Hg (P < 0.001), and sleep hours by 4.5 +/- 0.4 mm Hg (P = 0.004). DBP was lower following WATER compared to CONTROL: 1.2 +/- 0.3 mm Hg over 21 hours (P = 0.043); 0.9 +/- 0.6 mm Hg over awake hours (P = 0.101); and 1.4 +/- 0.9 mm Hg over sleep hours (P = 0.039). CONCLUSIONS: Aquatic exercise elicited PEH (~5 mm Hg) over 21 hours, BP reductions that are comparable in magnitude to land aerobic exercise. The immediate antihypertensive benefits of acute aquatic exercise should continue to be explored in future studies. PMID- 28985280 TI - Liquid Chromatographic Chiral Separation of Acenocoumarol and Its Hemiketal Form. AB - Acenocoumarol, an anticoagulant drug, was separated successfully using polysaccharide-based chiral stationary phases columns namely Cellulose Chiralpak(r) IB and Chiralcel(r) OD, using various normal mobile phases by high performance liquid chromatography. However, the appearance of four well separated peaks confirmed the presence of the hemiketal form of 4-hydroxy-3-[1-(4 nitrophenyl)-3-oxobutyl]-2H-chromen-2-one. PMID- 28985282 TI - The Renaissance of Heart Rate Variability as a Predictor of Cognitive Functioning. PMID- 28985281 TI - Striatin Gene Polymorphic Variants Are Associated With Salt Sensitive Blood Pressure in Normotensives and Hypertensives. AB - BACKGROUND: Understanding the interactions between genetics, sodium (Na+) intake, and blood pressure (BP) will help overcome the lack of individual specificity in our current treatment of hypertension. This study had 3 goals: expand on the relationship between striatin gene (STRN) status and salt-sensitivity of BP (SSBP); evaluate the status of Na+ and volume regulating systems by striatin risk allele status; evaluate potential SSBP mechanisms. METHODS: We assessed the relationship between STRN status in humans (HyperPATH cohort) and SSBP and on volume regulated systems in humans and a striatin knockout mouse (STRN+/-). RESULTS: The previously identified association between a striatin risk allele and systolic SSBP was demonstrated in a new cohort (P = 0.01). The STRN-SSBP association was significant for the combined cohort (P = 0.003; beta = +5.35 mm Hg systolic BP/risk allele) and in the following subgroups: normotensives, hypertensives, men, and older subjects. Additionally, we observed a lower epinephrine level in risk allele carriers (P = 0.014) and decreased adrenal medulla phenylethanolamine N-methyltransferase (PNMT) in STRN+/- mice. No significant associations were observed with other volume regulated systems. CONCLUSIONS: These results support the association between a variant of striatin and SSBP and extend the findings to normotensive individuals and other subsets. In contrast to most salt-sensitive hypertensives, striatin-associated SSBP is associated with normal plasma renin activity and reduced epinephrine levels. These data provide clues to the underlying cause and a potential pathway to achieve, specific, personalized treatment, and prevention. PMID- 28985283 TI - Renin-Angiotensin-Aldosterone System Parameters as Biomarker in Heart Failure Patients With Preserved Ejection Fraction: Focus on Angiotensinogen. PMID- 28985285 TI - Masked Uncontrolled Hypertension in the Elderly: A Dangerous Affair. PMID- 28985284 TI - Determination of Five Aminoalcohol-diterpenoid Alkaloids in the Lateral Root of Aconitum carmichaeli by HPLC-ELSD with SPE. AB - A convenient and accurate high-performance liquid chromatography coupled with evaporative light scattering detection (HPLC-ELSD) method using solid phase extraction (SPE) was established for quantification of five aminoalcohol diterpenoid alkaloids (ADAs), including mesaconine, aconine, hypaconine, fuziline and neoline, in the lateral roots of Aconitum carmichaeli (Fuzi) for the first time. The Fuzi extractive was purified using strong cation-exchange SPE. The chromatographic separation was performed on a Gemini C18 column (150 * 4.60 mm, 5 MUm) with the mobile phase of methanol-water-diethylamine (48:52:0.01, v/v/v), adjusted to pH 10.2 with acetic acid. The detector was Alltech ELSD 2000ES (drift tube temperature: 90 degrees C; gas flow-rate: 2.3 L/min). Five ADAs in Fuzi were well separated. The calibration curves showed good linearity (r > 0.9990) in the range of 0.0125-0.3750 mg/mL for each alkaloid. The recoveries were in the range of 95.1-105.7%, with relative standard deviations < 5.0%. This method is accurate, specific and repeatable for the determination of five ADAs in different Fuzi samples, which can be applied to the quality control of Fuzi. PMID- 28985286 TI - Australian employee perceptions of an organizational-level intervention to reduce sitting. AB - Stand Up Lendlease-a cluster-randomized trial targeting reductions in sitting time in Australian office workers (n = 153, 18 manager-led teams, 1 organization) effectively reduced sitting time during work hours and across the day after 12 months. The trial included two arms: organizational-support strategies (e.g. manager support, emails) with or without an activity tracker. The current study aimed to examine participant perceptions of the intervention, and perceived barriers and facilitators for reducing sitting time. Telephone interviews (n = 50 participants; conducted at 6-10 months) and three focus groups (n = 21 participants; conducted at 16 months) evaluated the intervention with qualitative data analysed thematically. Several consistent themes emerged across both short and long-term time points and intervention groups. Support and role modelling of desired behaviours from important organization personnel and receiving feedback on sitting levels were key drivers of change. Improvements in awareness about sitting, and workplace culture changes supporting active work practices were positive impacts of the intervention, but some participants also reported that initial cultural effects had dissipated and the intervention needed 'reinvigoration'. Participants desired additional 'tools' to maintain sitting less and being active, such as sit-stand desks, standing meeting tables and activity trackers. In summary, the intervention raised awareness and initiated cultural changes towards active work practices, however, additional support may be required to maintain changes in organizational culture long term. Practical tools to support sitting changes, organizational and management support and role modelling, as well as ongoing 'reinvigoration' are key strategies for short and long-term intervention success in office workplaces. PMID- 28985287 TI - Bariatric Surgery and Hypertension. AB - Obesity continues to increase in prevalence worldwide. Hypertension has long been associated with obesity, and weight loss continues to be a first-line therapy in the treatment of hypertension. Lifestyle modification and pharmacologic therapy, however, often meet with treatment failure. Bariatric surgery continues to be the most successful approach to sustained weight loss. This review focuses on the underlying physiologic mechanisms of obesity-hypertension, and the impact of bariatric surgery on the treatment of hypertension. Current available literature on the physiologic mechanisms of obesity-hypertension, and the major trials, meta analyses and systematic reviews of the impact of bariatric surgery procedures on hypertension are reviewed. Evidence suggests significant improvement in obesity hypertension in patients who undergo surgical weight-reduction procedures. Malabsorptive techniques such as the Roux-en-Y gastric bypass or surgical resection techniques such as laparoscopic sleeve gastrectomy appear to offer superior results in regards to hypertension control over restrictive techniques such as Gastric Banding. Though long-term control of hypertension following surgery remains a concern, available follow-up post-operative data of up to 10 years suggests a sustained, if lessened, effect on hypertension control over time. PMID- 28985289 TI - Hypertension and Atrial Fibrillation: Balancing Stroke and Bleeding Risks. PMID- 28985288 TI - Is orthostatic hypotension more common in individuals with atrial fibrillation? Findings from The Irish Longitudinal Study on Ageing (TILDA). AB - Introduction: atrial fibrillation (AF) and orthostatic hypotension (OH) share common risk factors such as age, hypertension and cardiovascular (CV) disease. The autonomic nervous system (ANS) also plays a role in the pathogenesis of both AF and OH. The aim of this study is to assess whether individuals with AF are more likely to have OH than those without AF. Methods: data from wave 1 of The Irish Longitudinal Study on Ageing were used. Beat-to-beat blood pressure was measured during active stand lasting 110 s. OH, defined as a drop in systolic blood pressure (SBP) >=20 mmHg or a drop in diastolic blood pressure >=10 mmHg at 30, 60 and 90 s was assessed. Initial OH (IOH) was assessed as a drop in SBP >=40 mmHg or a drop in diastolic BP>=20 mmHg. Results: in total 4,408 participants aged >=50 had active stand and electrocardiogram data suitable for analysis. AF was identified in 101 of these. Logistic regression found participants with AF were more likely to have OH at 30 (odds ratio (OR) 1.95, 95% confidence interval (CI) 1.24-3.06) and 60 (OR 2.13, 95% CI 1.18-3.87) seconds, and IOH (OR 1.81, 95% CI 1.21-2.70). The association between IOH and OH at 30 s remained significant following adjustment for confounders (age, sex, baseline HR, education, BP, smoking, frailty, beta blocker (BB) use, anti-hypertensive use (excluding BBs) and number of CV conditions). Conclusion: OH is more common in individuals with AF, this may reflect the role of the ANS in both AF and OH. PMID- 28985290 TI - Shared genetic influence on frailty and chronic widespread pain: a study from TwinsUK. AB - Introduction: frailty is an increased vulnerability to adverse health outcomes, across multiple physiological systems, with both environmental and genetic drivers. The two most commonly used measures are Rockwood's frailty index (FI) and Fried's frailty phenotype (FP). Material and methods: the present study included 3626 individuals from the TwinsUK Adult Twin Registry. We used the classical twin model to determine whether FI and FP share the same latent aetiological factors. We also investigated the relationship between frailty and chronic widespread musculoskeletal pain (CWP), another holistic age-related condition with significant clinical impact. Results: FP and FI shared underlying genetic and environmental aetiology. CWP was associated with both frailty measures, and health deficits appeared to mediate the relationship between phenotypic frailty and pain. Latent genetic factors underpinning CWP were shared with frailty. While frailty was increased in the twins reporting pain, co-twin regression analysis indicated that the relationship between CWP and frailty is reduced after accounting for shared genetic and environmental factors. Conclusions: both measures of frailty tap the same root causes, thus this work helps unify frailty research. We confirmed a strong association between CWP and frailty, and showed a large and significant shared genetic aetiology of both phenomena. Our findings argue against pain being a significant causative factor in the development of frailty, favouring common causation. This study highlights the need to manage CWP in frail individuals and undertake a Comprehensive Geriatric Assessment in individuals presenting with CWP. Finally, the search for genetic factors underpinning CWP and frailty could be aided by integrating measures of pain and frailty. PMID- 28985293 TI - Qualitative research on infertile Chinese couples' understanding of sexuality. AB - Background: Family physicians play an important role in the initial counselling and evaluation of infertility. Despite infertility regarded as a stressor and a life crisis for individuals or couples, little is known about the psychosexual aspects of infertility. On the basis that sexuality is a crucial part of quality of life, it is worthwhile to give more attention to sexuality of infertile couples during their time of experiencing infertility. Objective: This study aimed to gain insight into the dynamic features of the sexuality of infertile couples and to provide meaningful evidence for improving their quality of life. Methods: We employed a qualitative approach to conduct this study. Utilizing purposive sampling method, 56 participants (28 infertile Chinese couples) were recruited from the reproductive medicine centre of a general hospital, and in depth interviews were conducted with each participant. Thematic content analysis was used to analyse the transcripts. Results: Four themes emerged from the respondents' narratives; these themes relate to the infertile couples' understanding of sexuality: (i) gender identity, (ii) communication about sex, (iii) sexual life and (iv) sexual satisfaction. It was further found that Chinese culture's values of fertility, perceptions about sexuality and sex, social norms regarding gender, and expectations about marital sexual life can have significant effects on infertile Chinese couples' sexuality. Conclusion: These findings should be highly considered by family physicians in their practice to provide infertile couples with information related to sexual well-being, coping styles, relationship, etc. PMID- 28985292 TI - Extreme Deviations from Expected Evolutionary Rates in Archaeal Protein Families. AB - Origin of new biological functions is a complex phenomenon ranging from single nucleotide substitutions to the gain of new genes via horizontal gene transfer or duplication. Neofunctionalization and subfunctionalization of proteins is often attributed to the emergence of paralogs that are subject to relaxed purifying selection or positive selection and thus evolve at accelerated rates. Such phenomena potentially could be detected as anomalies in the phylogenies of the respective gene families. We developed a computational pipeline to search for such anomalies in 1,834 orthologous clusters of archaeal genes, focusing on lineage-specific subfamilies that significantly deviate from the expected rate of evolution. Multiple potential cases of neofunctionalization and subfunctionalization were identified, including some ancient, house-keeping gene families, such as ribosomal protein S10, general transcription factor TFIIB and chaperone Hsp20. As expected, many cases of apparent acceleration of evolution are associated with lineage-specific gene duplication. On other occasions, long branches in phylogenetic trees correspond to horizontal gene transfer across long evolutionary distances. Significant deceleration of evolution is less common than acceleration, and the underlying causes are not well understood; functional shifts accompanied by increased constraints could be involved. Many gene families appear to be "highly evolvable," that is, include both long and short branches. Even in the absence of precise functional predictions, this approach allows one to select targets for experimentation in search of new biology. PMID- 28985294 TI - Recruiting primary care practices for practice-based research: a case study of a group-randomized study (TRANSLATE CKD) recruitment process. AB - Background: We assessed the challenging process of recruiting primary care practices in a practice-based research study. Methods: In this descriptive case study of recruitment data collected for a large practice-based study (TRANSLATE CKD), 48 single or multiple-site health care organizations in the USA with a total of 114 practices were invited to participate. We collected quantitative and qualitative measures of recruitment process and outcomes for the first 25 practices recruited. Information about 13 additional practices is not provided due to staff transitions and limited data collection resources. Results: Initial outreach was made to 114 practices (from 48 organizations, 41% small); 52 (45%) practices responded with interest. Practices enrolled in the study (n = 25) represented 22% of the total outreach number, or 48% of those initially interested. Average time to enroll was 71 calendar days (range 11-107). There was no difference in the number of days practices remained under recruitment, based on enrolled versus not enrolled (44.8 +/- 30.4 versus 46.8 +/- 25.4 days, P = 0.86) or by the organization size, i.e. large versus small (defined by having <=4 distinct practices; 52 +/- 23.6 versus 43.6 +/- 27.8 days; P = 0.46). The most common recruitment barriers were administrative, e.g. lack of perceived direct organizational benefit, and were more prominent among large organizations. Conclusions: Despite the general belief that the research topic, invitation method, and interest in research may facilitate practice recruitment, our results suggest that most of the recruitment challenges represent managerial challenges. Future research projects may need to consider relevant methodologies from businesses administration and marketing fields. PMID- 28985291 TI - Mobile Genetic Elements and Evolution of CRISPR-Cas Systems: All the Way There and Back. AB - The Clustered Regularly Interspaced Palindromic Repeats (CRISPR)-CRISPR associated proteins (Cas) systems of bacterial and archaeal adaptive immunity show multifaceted evolutionary relationships with at least five classes of mobile genetic elements (MGE). First, the adaptation module of CRISPR-Cas that is responsible for the formation of the immune memory apparently evolved from a Casposon, a self-synthesizing transposon that employs the Cas1 protein as the integrase and might have brought additional cas genes to the emerging immunity loci. Second, a large subset of type III CRISPR-Cas systems recruited a reverse transcriptase from a Group II intron, providing for spacer acquisition from RNA. Third, effector nucleases of Class 2 CRISPR-Cas systems that are responsible for the recognition and cleavage of the target DNA were derived from transposon encoded TnpB nucleases, most likely, on several independent occasions. Fourth, accessory nucleases in some variants of types I and III toxin and type VI effectors RNases appear to be ultimately derived from toxin nucleases of microbial toxin-antitoxin modules. Fifth, the opposite direction of evolution is manifested in the recruitment of CRISPR-Cas systems by a distinct family of Tn7 like transposons that probably exploit the capacity of CRISPR-Cas to recognize unique DNA sites to facilitate transposition as well as by bacteriophages that employ them to cope with host defense. Additionally, individual Cas proteins, such as the Cas4 nuclease, were recruited by bacteriophages and transposons. The two-sided evolutionary connection between CRISPR-Cas and MGE fits the "guns for hire" paradigm whereby homologous enzymatic machineries, in particular nucleases, are shuttled between MGE and defense systems and are used alternately as means of offense or defense. PMID- 28985296 TI - The association between implementation and outcome of a complex care program for frail elderly people. AB - Background: Over the last 20 years, the effectiveness of complex care programs aiming to prevent adverse outcomes in frail elderly people has been disappointing. Recently, we found no effectiveness of the CareWell primary care program. It is largely unknown to what extent incomplete implementation of these complex interventions influences their outcomes. Objective: To examine the association between the degree of implementation of the CareWell program and the prevention of functional decline in frail elderly people. Methods: Quantitative process evaluation conducted alongside a cluster-controlled trial. Two hundred and four frail elderly participants from six general practitioner practices in the Netherlands received care according to the CareWell program, consisting of four key components: multidisciplinary team meetings, proactive care planning, case management and medication reviews. We measured time registrations of team meetings, case management and medication reviews and care plan data as stored in a digital information portal. These data were aggregated into a total implementation score (TIS) representing the program's overall implementation. We measured functional decline with the Katz-15 change score (follow-up score at 12 months minus the baseline score). The association between TIS and functional decline was analyzed with linear mixed model analyses. Results: We found no statistically significant differences in functional decline between TIS groups (F = 1.350, P = 0.245). In the groups with the highest TISs, we found more functional decline. Conclusion: A higher degree of implementation of the CareWell program did not lead to the prevention of functional decline in frail elderly people. PMID- 28985295 TI - Few Nuclear-Encoded Mitochondrial Gene Duplicates Contribute to Male Germline Specific Functions in Humans. AB - Most of the genes encoding proteins that function in the mitochondria are located in the nucleus and are called nuclear-encoded mitochondrial genes, or N-mt genes. In Drosophila melanogaster , about 23% of N-mt genes fall into gene families, and all duplicates with tissue-biased expression (76%) are testis biased. These genes are enriched for energy-related functions and tend to be older than other duplicated genes in the genome. These patterns reveal strong selection for the retention of new genes for male germline mitochondrial functions. The two main forces that are likely to drive changes in mitochondrial functions are maternal inheritance of mitochondria and male-male competition for fertilization. Both are common among animals, suggesting similar N-mt gene duplication patterns in different species. To test this, we analyzed N-mt genes in the human genome. We find that about 18% of human N-mt genes fall into gene families, but unlike in Drosophila , only 28% of the N-mt duplicates have tissue-biased expression and only 36% of these have testis-biased expression. In addition, human testis-biased duplicated genes are younger than other duplicated genes in the genome and have diverse functions. These contrasting patterns between species might reflect either differences in selective pressures for germline energy-related or other mitochondrial functions during spermatogenesis and fertilization, or differences in the response to similar pressures. PMID- 28985297 TI - Gene Regulatory Enhancers with Evolutionarily Conserved Activity Are More Pleiotropic than Those with Species-Specific Activity. AB - Studies of regulatory activity and gene expression have revealed an intriguing dichotomy: There is substantial turnover in the regulatory activity of orthologous sequences between species; however, the expression level of orthologous genes is largely conserved. Understanding how distal regulatory elements, for example, enhancers, evolve and function is critical, as alterations in gene expression levels can drive the development of both complex disease and functional divergence between species. In this study, we investigated determinants of the conservation of regulatory enhancer activity for orthologous sequences across mammalian evolution. Using liver enhancers identified from genome-wide histone modification profiles in ten diverse mammalian species, we compared orthologous sequences that exhibited regulatory activity in all species (conserved-activity enhancers) to shared sequences active only in a single species (species-specific-activity enhancers). Conserved-activity enhancers have greater regulatory potential than species-specific-activity enhancers, as quantified by both the density and diversity of transcription factor binding motifs. Consistent with their greater regulatory potential, conserved-activity enhancers have greater regulatory activity in humans than species-specific activity enhancers: They are active across more cellular contexts, and they regulate more genes than species-specific-activity enhancers. Furthermore, the genes regulated by conserved-activity enhancers are expressed in more tissues and are less tolerant of loss-of-function mutations than those targeted by species specific-activity enhancers. These consistent results across various stages of gene regulation demonstrate that conserved-activity enhancers are more pleiotropic than their species-specific-activity counterparts. This suggests that pleiotropy is associated with the conservation of regulatory across mammalian evolution. PMID- 28985299 TI - A multidisciplinary intervention programme for overweight and obese children in deprived areas. AB - Background: GPs can refer obese children living in deprived areas to multidisciplinary programmes for a weight loss intervention, though the effectiveness of these local initiatives targeted to this specific group is unknown. Objective: To evaluate the effectiveness of the Kids4Fit intervention in deprived areas on child's weight status. Methods: Design and setting: cohort study, including a waiting list control period. Subjects: children (N = 154) aged 6-12 years, who signed up for the Kids4Fit intervention programme, led by a dietitian, physiotherapist and child psychologist were included. Measurements of standardized body mass index (BMI-z) and waist circumference were taken at start of the waiting list period, at start and at the end of the intervention and after 52 weeks. Mixed model analyses (random effects models) were used, expressed in effect per week [beta with 95% confidence interval (CI)], compared to the waiting list expectancy over the 52-week study period. Results: Mixed model analyses showed a non-significant trend towards a lower BMI-z up to 52 weeks after start of Kids4Fit (beta: -0.0024; 95% CI: -0.0053; 0.0004), compared to the waiting list expectancy. A significantly lower waist circumference was found over time compared to the waiting list expectancy (beta: -0.0558; 95% CI: -0.0950; 0.0166). No differences were found in lifestyle and health-related quality of life. Conclusion: A local multidisciplinary intervention programme in deprived areas is effective in reducing waist circumference of obese children, compared to a waiting list expectancy, but no significant changes in lifestyle and quality of life were shown. PMID- 28985300 TI - Focus on early-career GPs: qualitative evaluation of a multi-faceted educational intervention to improve antibiotic prescribing. AB - Background: We conducted an educational intervention emphasizing rational antibiotic prescribing in early-career General Practitioners (GP) in vocational training (trainees). The intervention consisted of an online introduction module, an online communication training module, face-to-face workshops, and cases to be discussed one-on-one by the trainee-supervisor dyad during regular scheduled education sessions. Objectives: To explore the participants' experiences with the intervention. Methods: A qualitative study of 14 GP trainees and supervisors. Interviews followed a semi-structured interview guide, were transcribed and analysed using concurrent thematic analysis. Results: Overall, the intervention was well received. Resources were not often used in practice, but GP trainees used the information in communicating with patients. The intervention improved trainees' confidence and provided new communication strategies, e.g. explicitly asking about patients' expectations and talking patients through the examination to form an overall clinical picture. Trainees seemed eager to learn and adapt their practice, whereas GP supervisors rather commented that the intervention was reinforcing. None of the participants reported prescribing conflicts between trainee and supervisor. However, most participants identified conflicts within the GP practice or with specialists: other doctors who prescribe more antibiotics perpetuate patients' ideas that antibiotics will fix everything, which in turn causes conflict with the patient and undermines attempts to improve antibiotic prescribing. Conclusion: The educational intervention was received positively. Early-career GPs thought it influenced their prescribing behaviour and improved their confidence in non-prescribing. Interventions that target teams (e.g. entire practice) could minimize conflict, ensure consistency of messages and support overall antibiotic stewardship in primary care. PMID- 28985298 TI - Phylogenetic Conflict in Bears Identified by Automated Discovery of Transposable Element Insertions in Low-Coverage Genomes. AB - Phylogenetic reconstruction from transposable elements (TEs) offers an additional perspective to study evolutionary processes. However, detecting phylogenetically informative TE insertions requires tedious experimental work, limiting the power of phylogenetic inference. Here, we analyzed the genomes of seven bear species using high-throughput sequencing data to detect thousands of TE insertions. The newly developed pipeline for TE detection called TeddyPi (TE detection and discovery for Phylogenetic Inference) identified 150,513 high-quality TE insertions in the genomes of ursine and tremarctine bears. By integrating different TE insertion callers and using a stringent filtering approach, the TeddyPi pipeline produced highly reliable TE insertion calls, which were confirmed by extensive in vitro validation experiments. Analysis of single nucleotide substitutions in the flanking regions of the TEs shows that these substitutions correlate with the phylogenetic signal from the TE insertions. Our phylogenomic analyses show that TEs are a major driver of genomic variation in bears and enabled phylogenetic reconstruction of a well-resolved species tree, despite strong signals for incomplete lineage sorting and introgression. The analyses show that the Asiatic black, sun, and sloth bear form a monophyletic clade, in which phylogenetic incongruence originates from incomplete lineage sorting. TeddyPi is open source and can be adapted to various TE and structural variation callers. The pipeline makes it possible to confidently extract thousands of TE insertions even from low-coverage genomes (~10*) of nonmodel organisms. This opens new possibilities for biologists to study phylogenies and evolutionary processes as well as rates and patterns of (retro-)transposition and structural variation. PMID- 28985301 TI - The Trouble with MEAM2: Implications of Pseudogenes on Species Delimitation in the Globally Invasive Bemisia tabaci (Hemiptera: Aleyrodidae) Cryptic Species Complex. AB - Molecular species identification using suboptimal PCR primers can over-estimate species diversity due to coamplification of nuclear mitochondrial (NUMT) DNA/pseudogenes. For the agriculturally important whitefly Bemisia tabaci cryptic pest species complex, species identification depends primarily on characterization of the mitochondrial DNA cytochrome oxidase I (mtDNA COI) gene. The lack of robust PCR primers for the mtDNA COI gene can undermine correct species identification which in turn compromises management strategies. This problem is identified in the B. tabaci Africa/Middle East/Asia Minor clade which comprises the globally invasive Mediterranean (MED) and Middle East Asia Minor I (MEAM1) species, Middle East Asia Minor 2 (MEAM2), and the Indian Ocean (IO) species. Initially identified from the Indian Ocean island of Reunion, MEAM2 has since been reported from Japan, Peru, Turkey and Iraq. We identified MEAM2 individuals from a Peruvian population via Sanger sequencing of the mtDNA COI gene. In attempting to characterize the MEAM2 mitogenome, we instead characterized mitogenomes of MEAM1. We also report on the mitogenomes of MED, AUS, and IO thereby increasing genomic resources for members of this complex. Gene synteny (i.e., same gene composition and orientation) was observed with published B. tabaci cryptic species mitogenomes. Pseudogene fragments matching MEAM2 partial mtDNA COI gene exhibited low frequency single nucleotide polymorphisms that matched low copy number DNA fragments (<3%) of MEAM1 genomes, whereas presence of internal stop codons, loss of expected stop codons and poor primer annealing sites, all suggested MEAM2 as a pseudogene artifact and so not a real species. PMID- 28985303 TI - What do tests do for doctors? A qualitative study of blood testing in UK primary care. AB - Background: Rates of blood testing are rising with significant geographical variability. Most research into diagnostic testing focuses on the role of tests in diagnostic decision-making. Objective: The aim of this study was to explore the non-medical motives for blood testing by considering what tests do for doctors, through qualitative interviews with general practitioners (GPs). Methods: We undertook 23 in-depth semi-structured interviews with UK GPs. Reasons for performing recent inflammatory marker blood tests were explored by reviewing GPs pathology inboxes to ground discussions in real-life clinical practice. Interviews were transcribed verbatim and analysed using a grounded theory approach. Results: Blood tests offer doctors a tool to manage uncertainty; within a context of increased litigation, risk aversion and reduced continuity of care. Tests can also be offered as a 'gift' for patients, a way to be seen to be 'doing something'; in the social context of time pressures and perceived patient pressures. There was a tension however. On the one hand, doctors talked about using tests for reassurance and as a 'gift' offering 'truth'. Yet paradoxically, they also discussed the challenges of uncertainty and anxiety from inconclusive test results. Conclusion: Our study emphasises that defining 'unnecessary' blood testing may not be as simple as determining medical criteria for testing; psychosocial reasons may be equally valid and interlinked. Further research is needed to help GPs manage uncertainty within the context of a risk averse society, and to explore the congruence and dissonance between doctors' and patients' perceptions of testing. PMID- 28985304 TI - Treatment of nocturnal leg cramps by primary care patients over the age of 60. AB - Background: Approximately one out of two individuals over the age of 60 suffers from nocturnal leg cramps. These often have an important impact on the person's quality of life. Different drug and non-drug treatments are proposed to treat these cramps, but none to date have been shown to be both safe and effective. The objective of this study was to describe the drug and non-drug treatments used by primary care patients suffering from cramps. Methods: We used data collected as part of two cross-sectional surveys of patients aged 60 years and older attending general practices in the French region of Alsace. We asked the participants suffering from cramps if they were currently using a treatment for their cramps. We distinguished potentially harmful from unharmful treatments. Results: Overall, 632 patients suffering from cramps were included in our study. Only 133 patients (19.5%) were taking a treatment for cramps. 82 patients used one or several of 17 different drug treatments. 58 patients used one or several of 13 different types of non-drug treatments. Potentially harmful treatments, mostly Quinine made up 16,7% (n = 25) of all treatments used for cramps. Conclusions: This study sheds light on the great diversity of therapeutic practices for cramps in outpatient care. Many of the treatments reported by patients have not previously been described in the medical literature. We recommend GPs to ask their patients about the treatments they take for cramps in order to make sure that they are safe. PMID- 28985302 TI - Net Evolutionary Loss of Residue Polarity in Drosophilid Protein Cores Indicates Ongoing Optimization of Amino Acid Composition. AB - Amino acid frequencies in proteins may not be at equilibrium. We consider two possible explanations for the nonzero net residue fluxes in drosophilid proteins. First, protein interiors may have a suboptimal residue composition and be under a selective pressure favoring stability, that is, leading to the loss of polar (and the gain of large) amino acids. One would then expect stronger net fluxes on the protein interior than at the exposed sites. Alternatively, if most of the polarity loss occurs at the exposed sites and the selective constraint on amino acid composition at such sites decreases over time, net loss of polarity may be neutral and caused by disproportionally high occurrence of polar residues at exposed, least constrained sites. We estimated net evolutionary fluxes of residue polarity and volume at sites with different solvent accessibility in conserved protein families from 12 species of Drosophila. Net loss of polarity, miniscule in magnitude, but consistent across all lineages, occurred at all sites except the most exposed ones, where net flux of polarity was close to zero or, in membrane proteins, even positive. At the intermediate solvent accessibility the net fluxes of polarity and volume were similar to neutral predictions, whereas much of the polarity loss not attributable to neutral expectations occurred at the buried sites. These observations are consistent with the hypothesis that residue composition in many proteins is structurally suboptimal and continues to evolve toward lower polarity in the protein interior, in particular in proteins with intracellular localization. The magnitude of polarity and volume changes was independent from the protein's evolutionary age, indicating that the approach to equilibrium has been slow or that no such single equilibrium exists. PMID- 28985305 TI - Genome sequencing and comparative genomics reveal the potential pathogenic mechanism of Cercospora sojina Hara on soybean. AB - Frogeye leaf spot, caused by Cercospora sojina Hara, is a common disease of soybean in most soybean-growing countries of the world. In this study, we report a high-quality genome sequence of C. sojina by Single Molecule Real-Time sequencing method. The 40.8-Mb genome encodes 11,655 predicated genes, and 8,474 genes are revealed by RNA sequencing. Cercospora sojina genome contains large numbers of gene clusters that are involved in synthesis of secondary metabolites, including mycotoxins and pigments. However, much less carbohydrate-binding module protein encoding genes are identified in C. sojina genome, when compared with other phytopathogenic fungi. Bioinformatics analysis reveals that C. sojina harbours about 752 secreted proteins, and 233 of them are effectors. During early infection, the genes for metabolite biosynthesis and effectors are significantly enriched, suggesting that they may play essential roles in pathogenicity. We further identify 13 effectors that can inhibit BAX-induced cell death. Taken together, our results provide insights into the infection mechanisms of C. sojina on soybean. PMID- 28985306 TI - Plastome Evolution in the Sole Hemiparasitic Genus Laurel Dodder (Cassytha) and Insights into the Plastid Phylogenomics of Lauraceae. AB - To date, little is known about the evolution of plastid genomes (plastomes) in Lauraceae. As one of the top five largest families in tropical forests, the Lauraceae contain many species that are important ecologically and economically. Lauraceous species also provide wonderful materials to study the evolutionary trajectory in response to parasitism because they contain both nonparasitic and parasitic species. This study compared the plastomes of nine Lauraceous species, including the sole hemiparasitic and herbaceous genus Cassytha (laurel dodder; here represented by Cassytha filiformis). We found differential contractions of the canonical inverted repeat (IR), resulting in two IR types present in Lauraceae. These two IR types reinforce Cryptocaryeae and Neocinnamomum-Perseeae Laureae as two separate clades. Our data reveal several traits unique to Cas. filiformis, including loss of IRs, loss or pseudogenization of 11 ndh and rpl23 genes, richness of repeats, and accelerated rates of nucleotide substitutions in protein-coding genes. Although Cas. filiformis is low in chlorophyll content, our analysis based on dN/dS ratios suggests that both its plastid house-keeping and photosynthetic genes are under strong selective constraints. Hence, we propose that short generation time and herbaceous lifestyle rather than reduced photosynthetic ability drive the accelerated rates of nucleotide substitutions in Cas. filiformis. PMID- 28985308 TI - Development of a multi-component lifestyle intervention for preventing type 2 diabetes and cardiovascular risk factors in adults with intellectual disabilities. AB - Background: We report on the development of the 'STOP Diabetes' education programme, a multi-component lifestyle behaviour change intervention for the prevention of type 2 diabetes and cardiovascular risk factors in adults with intellectual disabilities (ID). Methods: We combined qualitative stakeholder interviews with evidence reviews to develop the intervention, guided by the MRC Framework and informed by intervention mapping and two existing diabetes prevention programmes. We conducted two pilot cycles drawing on additional stakeholder interviews to inform and refine the intervention. Results: The STOP Diabetes education programme employed a theoretical framework, using sound learning and behavioural principles and concrete kinaesthetic methods, to provide the grounding for innovative games and activities to promote health behaviour change in adults with ID. Qualitative data also suggested that two educators and one support person delivering a programme of one carer session followed by seven 2.5-h sessions over 7 weeks was acceptable to service users, carers and educators and appeared to benefit the participants. Conclusions: The STOP Diabetes education programme was successfully developed and is suitable for a definitive randomized controlled trial. PMID- 28985309 TI - Comparing watchful waiting with antidepressants for the management of subclinical depression symptoms to mild-moderate depression in primary care: a systematic review. AB - Background: The benefits of watchful waiting (WW) over antidepressants (ADs) for the treatment of depression in primary care (PC) are unclear. Objective: We aimed to systematically review the evidence supporting either WW or ADs for the treatment of subclinical depressive symptoms and mild-moderate depression in a PC setting. Methods: This systematic review was registered at PROSPERO (42016036345). Four electronic sources (EMBASE, PubMed, PsycINFO, Web of Knowledge) were systematically searched from inception to November 2016 for controlled trials comparing WW and ADs in PC following established guidelines. The studies had to include adult population with new symptoms of subclinical depression or mild-moderate depression. Patients in the intervention group should receive a WW approach, while patients in the control group underwent treatment with ADs. The abstraction form included information on the setting, characteristics of the study population, total sample size, size of the control and intervention groups and date of the study. Outcome measures and variability were extracted. Results: The scarcity of studies and the considerable clinical and methodological heterogeneity discouraged us from performing a meta-analysis. Three articles were included and qualitatively synthesized. There was no evidence for the superiority of one treatment option over the other, although two of the studies suggested small differences in favour of ADs when less conservative analyses were conducted (per protocol analysis and analysis not adjusted for missingness predictors). Conclusions: Superiority was not demonstrated by either treatment option. More robust evidence is needed to inform recommendations for the management of depressive symptoms in PC. PMID- 28985307 TI - Sequence-Based Analysis of Thermal Adaptation and Protein Energy Landscapes in an Invasive Blue Mussel (Mytilus galloprovincialis). AB - Adaptive responses to thermal stress in poikilotherms plays an important role in determining competitive ability and species distributions. Amino acid substitutions that affect protein stability and modify the thermal optima of orthologous proteins may be particularly important in this context. Here, we examine a set of 2,770 protein-coding genes to determine if proteins in a highly invasive heat tolerant blue mussel (Mytilus galloprovincialis) contain signals of adaptive increases in protein stability relative to orthologs in a more cold tolerant M. trossulus. Such thermal adaptations might help to explain, mechanistically, the success with which the invasive marine mussel M. galloprovincialis has displaced native species in contact zones in the eastern (California) and western (Japan) Pacific. We tested for stabilizing amino acid substitutions in warm tolerant M. galloprovincialis relative to cold tolerant M. trossulus with a generalized linear model that compares in silico estimates of recent changes in protein stability among closely related congeners. Fixed substitutions in M. galloprovincialis were 3,180.0 calories per mol per substitution more stabilizing at genes with both elevated dN/dS ratios and transcriptional responses to heat stress, and 705.8 calories per mol per substitution more stabilizing across all 2,770 loci investigated. Amino acid substitutions concentrated in a small number of genes were more stabilizing in M. galloprovincialis compared with cold tolerant M. trossulus. We also tested for, but did not find, enrichment of a priori GO terms in genes with elevated dN/dS ratios in M. galloprovincialis. This might indicate that selection for thermodynamic stability is generic across all lineages, and suggests that the high change in estimated protein stability that we observed in M. galloprovincialis is driven by selection for extra stabilizing substitutions, rather than by higher incidence of selection in a greater number of genes in this lineage. Nonetheless, our finding of more stabilizing amino acid changes in the warm adapted lineage is important because it suggests that adaption for thermal stability has contributed to M. galloprovincialis' superior tolerance to heat stress, and that pairing tests for positive selection and tests for transcriptional response to heat stress can identify candidates of protein stability adaptation. PMID- 28985311 TI - Response to: The Cause of the Arteriolar Injury in Malignant Hypertension. PMID- 28985310 TI - Outcomes of Mobilisation of Vulnerable Elders in Ontario (MOVE ON): a multisite interrupted time series evaluation of an implementation intervention to increase patient mobilisation. AB - Background: older patients admitted to hospitals are at risk for hospital acquired morbidity related to immobility. The aim of this study was to implement and evaluate an evidence-based intervention targeting staff to promote early mobilisation in older patients admitted to general medical inpatient units. Methods: the early mobilisation implementation intervention for staff was multi component and tailored to local context at 14 academic hospitals in Ontario, Canada. The primary outcome was patient mobilisation. Secondary outcomes included length of stay (LOS), discharge destination, falls and functional status. The targeted patients were aged >= 65 years and admitted between January 2012 and December 2013. The intervention was evaluated over three time periods-pre intervention, during and post-intervention using an interrupted time series design. Results: in total, 12,490 patients (mean age 80.0 years [standard deviation 8.36]) were included in the overall analysis. An increase in mobilisation was observed post-intervention, where significantly more patients were out of bed daily (intercept difference = 10.56%, 95% CI: [4.94, 16.18]; P < 0.001) post-intervention compared to pre-intervention. Hospital median LOS was significantly shorter during the intervention period (intercept difference = 3.45 days, 95% CI: [-6.67,-0.23], P = 0.0356) compared to pre-intervention. It continued to decrease post-intervention with significantly fewer days in hospital (intercept difference= -6.1, 95% CI: [-11,-1.2]; P = 0.015) in the post intervention period compared to pre-intervention. Conclusions: this is a large scale study evaluating an implementation strategy for early mobilisation in older, general medical inpatients. The positive outcome of this simple intervention on an important functional goal of getting more patients out of bed is a striking success for improving care for hospitalised older patients. PMID- 28985312 TI - Maternal Renovascular Hypertensive Rats Treatment With Hydrogen Sulfide Increased the Methylation of AT1b Gene in Offspring. AB - BACKGROUND: A large number of studies have shown hypertension of offspring in adulthood is related to parental health during pregnancy. Hydrogen sulfide (H2S) could relax placental vasculature and improve intrauterine growth restriction. In the present study, we want to observe the effect of H2S on the fetal programming of renovascular hypertension, a rat model of secondary hypertension. METHODS: Renovascular hypertension was induced by 2-kidney-1-clip, their adult pups were used to evaluate basal blood pressure. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured noninvasively by tail-cuff plethysmography in conscious offspring; HE staining was used to observe morphology of kidney; the protein expression of angiotensin II receptor 1 (AT1R) tested by western blot; methylation of angiotensin II receptor 1b (AT1b) gene used pBLUE-T-cloning to check. RESULTS: The SBP and DBP in the offspring of renovascular hypertensive dams were higher than those in control group. Moreover, interstitial inflammatory infiltration was significant in the kidney and the protein expression of AT1R was also increased in the offspring of renovascular hypertensive dams. Conversely, methylation of AT1b promoter (U01033 277-1611) decreased in the first 3 CG sites. Either prenatal or postnatal treatment with H2S could increase the methylation of AT1b and downregulate AT1R expression then improve the blood pressure. CONCLUSION: These results suggested that parental secondary hypertension-induced kidney damage that elevated basal blood pressure in adult offspring. Prenatal or postnatal administration with H2S induced improved effect accompanied by an increased methylation of AT1b gene then downregulated protein of AT1R in offspring. PMID- 28985313 TI - General practitioners' perceptions of irritable bowel syndrome: a Q methodological study. AB - Background: Irritable bowel syndrome (IBS) is a common disorder that imposes a significant burden upon societies, health care and quality of life, worldwide. While a diverse range of patient viewpoints on IBS have been explored, the opinions of the GPs they ideally need to develop therapeutic partnerships with are less well defined. Objective: To explore how GPs perceive IBS, using Q methodology, which allows quantitative interpretation of qualitative data. Design and Setting: A Q-methodological study of GPs in Leeds, UK. Method: Thirty-three GPs completed an online Q-sort in which they ranked their level of agreement with 66 statements. Factor analysis of the Q-sorts was performed to determine the accounts that predominated in understandings of IBS. Ten of the GPs were interviewed in person and responses to the statements recorded to help explain the accounts. Results: Analysis yielded one predominant account shared by all GPs that IBS was a largely psychological disorder. This account overshadowed a debate represented by a minority, polarized between those who viewed IBS as almost exclusively psychological, versus those who believed IBS had an organic basis, with a psychological component. The overwhelming similarity in responses indicates that all GPs shared a common perspective on IBS. Interviews suggested degrees of uncertainty and discomfort around the aetiology of IBS. Conclusion: There was overwhelming agreement in the way GPs perceived IBS. This contrasts with the range of patient accounts of IBS and may explain why both GPs and their patients face difficult negotiations in achieving therapeutic relationships. PMID- 28985314 TI - To Become Senders, Songbirds Must be Receivers First. AB - Courtship signals are attractive; in other words, receivers are motivated to approach courtship signals. Though the concept of a receiver is commonly associated in the literature with that of a mate seeker, young songbirds that are learning to sing by imitating conspecifics are also receivers. Juvenile songbirds are attracted to conspecific songs, which has been shown by juveniles working to hear song in operant chambers. The mechanisms explaining this attraction are poorly understood. Here, I review studies that hint at the mechanisms by which conspecific song becomes attractive. In at least some species, juveniles imitate individuals with which they have a strong social bond, such as the father. Such cases suggest that social reward plays a role in the process of song becoming attractive. In addition, experiments using birds reared in isolation from conspecific song have shown that juveniles imitate songs that have acoustic features that are typically found in conspecific song. Those studies suggest that such features are attractive to juveniles regardless of their social experience. The relative contributions of social reward and species-typical acoustic features to the attractiveness of a song can be determined using methods such as operant conditioning. For example, juvenile songbirds can be given control over the playback of songs that differ in a given attribute, such as acoustic similarity to the song of the father. The juveniles will frequently elicit playback of the songs that are attractive to them. Investigating the mechanisms that contribute to the attractiveness of conspecific song to learners will broaden our understanding of the evolution of song as a courtship signal, because the preferences of learners may ultimately determine what will be sung to potential mates. PMID- 28985316 TI - Are RNA Viruses Candidate Agents for the Next Global Pandemic? A Review. AB - Pathogenic RNA viruses are potentially the most important group involved in zoonotic disease transmission, and they represent a challenge for global disease control. Their biological diversity and rapid adaptive rates have proved to be difficult to overcome and to anticipate by modern medical technology. Also, the anthropogenic change of natural ecosystems and the continuous population growth are driving increased rates of interspecies contacts and the interchange of pathogens that can develop into global pandemics. The combination of molecular, epidemiological, and ecological knowledge of RNA viruses is therefore essential towards the proper control of these emergent pathogens. This review outlines, throughout different levels of complexity, the problems posed by RNA viral diseases, covering some of the molecular mechanisms allowing them to adapt to new host species-and to novel pharmaceutical developments-up to the known ecological processes involved in zoonotic transmission. PMID- 28985315 TI - Cross-Reactivity of Pantoprazole with Three Commercial Cannabinoids Immunoassays in Urine. AB - Pantoprazole is a frequently prescribed proton pump inhibitor (PPI) commonly utilized in the management of gastrointestinal symptoms. Few substances have proved to cause a false-positive cannabinoid urine screen. However, a case of false-positive urine cannabinoid screen in a patient who received a pantoprazole dose has been recently published. The purpose of this study was to determine the potential cross-reactivity of pantoprazole in the cannabinoid immunoassays: Alere Triage(r) TOX Drug Screen, KIMS(r) Cannabinoids II and DRI(r) Cannabinoids Assay. Drug-free urine to which pantoprazole was added up to 12,000 MUg/mL produced negative results in the DRI(r) Cannabinoids and KIMS(r) Cannabinoids II. Alere Triage(r) TOX Drug Screen assay gave positive results at pantoprazole concentrations higher than 1,000 MUg/mL. Urine samples from 8 pediatric patients were collected at the beginning of their pantoprazole treatment. Alere Triage(r) TOX Drug Screen assay produced positive test results in all patient samples and KIMS(r) Cannabinoids II immunoassay produced positive test results in one patient sample. None patient sample gave a false-positive result when analyzed by the DRI(r) Cannabinoids Assay. Our findings demonstrate that some cannabinoids immunoassays are susceptible to cross-reaction errors resulting from the presence in urine of pantoprazole and the resulting metabolism of the parent drug. Clinicians should be aware of the possibility of false-positive results for cannabinoids after a pantoprazole treatment. PMID- 28985317 TI - Manipulation of Gut Microbiota Reveals Shifting Community Structure Shaped by Host Developmental Windows in Amphibian Larvae. AB - Exploration of the importance of developmental windows for microbial colonization in diverse animal taxa, and tests of how these shape both animal microbiomes as well as host phenotypes promise to shed needed light on host-microbe interactions. The aims of this study were to explore how gut microbiota diversity of larval amphibians varies among species and across ontogeny, and to test if manipulation of gut colonization can reveal how microbiomes develop. We found that gut microbiomes differ among species and change across larval ontogeny, with distinctive differences between larvae, metamorphic animals, and juvenile frogs. Through applying a gnotobiotic protocol to eggs and cross-inoculating gut microbiomes between species, we demonstrated that microbiota can be transplanted among species and developmental stages. These results also demonstrated that microbial colonization at hatching is potentially formative for long term composition and function of amphibian gut microbiomes, suggesting that hatching may be a critical developmental window for colonization, similar to the effects of birth mode on human microbiomes. Specifically, our results suggest that either the egg jelly and/or capsules surrounding amphibian eggs are likely important sources for initial microbiome inoculation. Furthermore, we speculate these results suggest that vertical transmission may be important to amphibian microbiome establishment and development, as is common among many animal taxa. Taken together, our results suggest that explicit tests of how host developmental windows influence microbial colonization, and shape amphibian microbiomes across life stages promise to provide insight into the ecological and evolutionary dynamics of host-microbe interactions. PMID- 28985319 TI - Rift Valley Fever: Does Wildlife Play a Role? AB - Rift Valley fever (RVF) virus (RVFV) is an emerging vector-borne pathogen that causes sporadic epizootics and epidemics with multi-year, apparently quiescent, inter-epidemic periods. The epidemiology and ecology of the virus during these inter-epidemic periods is poorly understood. There is evidence for low-level circulation of the virus in livestock and wild ruminants; however, as of yet there is no evidence to identify a specific mammalian reservoir host. Using a systematic approach, this review synthesizes results from serosurveys, attempts at viral detection, and experimental infection of wildlife. These data demonstrate there is a gap in research conducted on RVF in wild ruminants. Specifically, there is very little published data on the pathogenicity of an RVFV infection in various wildlife species, validation of diagnostic assays for exposure to RVFV and understanding of epizootic or endemic disease dynamics in wild ruminants. We recommend that future research on RVFV incorporate a more systematic approach to understand the low-level cycling of the virus during inter epidemic periods in both wild and domestic ruminant species. PMID- 28985318 TI - Nonhuman Primates: A Vital Model for Basic and Applied Research on Female Reproduction, Prenatal Development, and Women's Health. AB - The comparative biology of reproduction and development in mammalian species is remarkable. Hence, because of similarities in environmental and neuroendocrine control of the reproductive axis, the cyclic function of the ovary and reproductive tract, establishment and control of the maternal-fetal-placental unit during pregnancy, and reproductive aging from puberty through menopause, nonhuman primates (NHPs) are valuable models for research related to women's reproductive health and its disorders. This chapter provides examples of research over the past 10+ years using Old World monkeys (notably macaque species), baboons, and to a lesser extent New World monkeys (especially marmosets) that contributed to our understanding of the etiology and therapies or prevention of: (1) ovarian disorders, e.g., polycystic ovary syndrome, mitochondrial DNA-based diseases from the oocyte; (2) uterine disorders, for example, endometriosis and uterine transplantation; and (3) pregnancy disorders, for example, preterm labor and delivery, environmental factors. Also, emerging opportunities such as viral (e.g., Zika) induced fetal defects and germline genomic editing to generate valuable primate models of human diseases (e.g., Huntington and muscular dystrophy) are addressed. Although the high costs, specialized resources, and ethical debate challenge the use of primates in biomedical research, their inclusion in fertility and infertility research is vital for continued improvements in women's reproductive health. PMID- 28985321 TI - Intra-laboratory Development and Evaluation of a Quantitative Method for Measurement of Aflatoxins B1, M1 and Q1 in Animal Urine by High Performance Liquid Chromatography with Fluorescence Detection. AB - Mycotoxins negatively impact animal health. Aflatoxins (AFs) are the most common mycotoxins affecting both large and small animals and are a common cause of toxin related pet food recalls. Definitive diagnosis of aflatoxicosis is constrained by a lack of validated ante-mortem analytical methods for detection and quantitation of AFs and their metabolites in biological specimens. Herein, we developed and evaluated a urine-based quantitative method for measurement of aflatoxin B1 (AFB1) and its metabolites aflatoxin M1 (AFM1) and aflatoxin Q1 (AFQ1) in animal urine. (Some of the results have been presented at 59th AAVLD conference, Greensboro, North Carolina, October 13-19th, 2016.) This method uses an immuno affinity column for clean-up and pre-column derivatization followed by high performance liquid chromatography analysis with fluorescence detection. The method has high selectivity, recovery (>81%) and sensitivity with an instrument limit of detection of 0.20-1.02 pg; instrument limit of quantitation of 0.77-4.46 pg; and a method lower limit of quantitation of 0.30-2.5 ng/mL. The method has high accuracy, repeatability, and is rugged against minor changes. However, because of poor sensitivity of AFQ1 at low concentrations we recommend this method for quantitative determination of AFB1 and AFM1, and for qualitative measurement of AFQ1 in animal urine for diagnosis of aflatoxicosis. PMID- 28985320 TI - Multiple Drug-Toxicity Involving Novel Psychoactive Substances, 3 Fluorophenmetrazine and U-47700. AB - 3-Fluorophenmetrazine (3-FPM) is a stimulant-like novel psychoactive substance (NPS) and fluorinated analog of phenmetrazine that has recently appeared on the recreational drug market, with limited published information. Likewise, the synthetic opioid U-47700 has gained popularity among recreational drug users and is frequently detected in postmortem casework. We present the case history, autopsy and toxicological findings of a fatality involving the designer drugs 3 FPM and U-47700 for the first time in the literature. A sensitive and specific liquid chromatography-tandem mass spectrometry method was developed and validated for the quantification of 3-FPM in whole blood, with a 0.001-0.100 mg/L analytical range. The method met the requirements for acceptable linearity, bias and precision. 3-FPM was detected along with U-47700 and other drugs including amitriptyline, nortriptyline, methamphetamine, amphetamine, diazepam, nordiazepam, temazepam, and the designer benzodiazepines flubromazolam and delorazepam. 3-FPM was quantified in the decedent's peripheral (femoral) and central (aortic) blood at 2.4 and 2.6 mg/L, respectively. These concentrations are similar to reported concentrations in non-fatal intoxications. U-47700 was present in peripheral blood at a semi-quantitative concentration of 0.36 mg/L, consistent with reported U-47700 postmortem concentrations. The cause of death was considered multiple drug-toxicity (3-FPM, U-47700, amitriptyline, methamphetamine, diazepam, temazepam, flubromazolam and delorazepam) and the manner of death ruled an accident. This case illustrates the dangers of polysubstance use and discusses the potential overlap between recreational and fatal concentrations for some NPS. PMID- 28985322 TI - Chemical Evaluation of Electronic Cigarettes: Multicomponent Analysis of Liquid Refills and their Corresponding Aerosols. AB - Electronic cigarette use has raised concern worldwide regarding potential health risks and its position in tobacco cessation strategies. As part of any toxicity assessment, the chemical characterization of e-liquids and their related vapors are among fundamental data to be determined. Considering the lack of available reference methods, we developed and validated several analytical procedures in order to conduct a multicomponent analysis of six e-liquid refills and their resultant vapor emissions (generated by a smoking machine), and compared them with tobacco smoke. We combined several techniques including gas-chromatography, high and ultra-performance liquid chromatography and inductively coupled plasma with mass spectrometry or ultraviolet and flame ionization detection in order to identify the main e-liquid constituents (propylene glycol, glycerol and nicotine), as well as multiple potentially harmful components (trace elements, polycyclic aromatic hydrocarbons (PAHs), pesticides and carbonyl compounds). Regarding propylene glycol, glycerol and nicotine concentrations, the six tested e-liquids comply with the advertised composition and contain only traces of pollutants. Noticeable lower concentrations of trace elements (<=3.4 pg/mL puff), pesticides (=65 years in China, India, Cuba, Dominican Republic, Peru, Venezuela, Mexico and Puerto Rico in 2003. SRH was assessed by asking 'how do you rate your overall health in the past 30 days' with responses ranging from excellent to poor. Covariates included socio-demographic characteristics, use of health services and health factors. Mortality was ascertained through a screening of all respondents until 2007. Results: the prevalence of good SRH was higher in urban compared to rural sites, except in China. Men reported higher SRH than women, and depression had the largest negative impact on SRH in all sites. Without adjustment, those with poor SRH showed a 142% increase risk of dying within 4 years compared to those with moderate SRH. After adjusting for all covariates, those with poor SRH still showed a 43% increased risk. Conclusion: our findings support the use of SRH as a simple measure in survey settings to identify vulnerable groups and evaluate health interventions in resource-scares settings. PMID- 28985332 TI - Trade-offs Influencing the Physiological Ecology of Hibernation in Temperate-Zone Bats. AB - Seasonality of temperature and food availability can lead to trade-offs between the benefits of immediate reproduction and costs associated with mortality risk from starvation, inclement weather, or predation. Hibernating mammals exhibit an enormous seasonal shift in physiology and behavior and provide a useful system to examine the effect of this trade-off on key events in the annual cycle. Most of what we understand about the ecological energetics and phenology of hibernation comes from studies of rodent hibernators such as ground squirrels, chipmunks, and dormice. Temperate-zone, insectivorous bats, however, provide another useful model system to examine trade-offs influencing seasonal change within individuals. Here, I review recent studies from my laboratory on little brown bats (Myotis lucifugus) from central Canada to understand the interplay between capacity for energy storage, energy expenditure during hibernation, and the timing of key events in the annual cycle of hibernating mammals. These studies have relied on measurements of body condition to assess energetic status, biologging of skin temperature using temperature telemetry, and use of passive transponders (i.e., PIT tags) to quantify emergence timing. In general, these studies suggest that, in part due to constraints associated with flight, bats exhibit unique, or at least unusual, adaptations for extreme energy savings during winter. The results also support the optimization hypothesis that current energetic status and future energy requirements influence energy expenditure during hibernation and the timing of emergence from hibernation in spring. Taken together, this work provides insight into the influence of reproductive timing and energy availability on hibernation behavior and physiology. It also has implications for understanding responses of bat populations to anthropogenic impacts like climate change and white-nose syndrome. PMID- 28985334 TI - Simultaneous Quantitation of Methamphetamine, Ketamine, Opiates and their Metabolites in Urine by SPE and LC-MS-MS. AB - Heroin, methamphetamine and ketamine have been the most commonly abused drugs in Taiwan. The presence of these drugs and their metabolites in postmortem specimens has been routinely monitored in our laboratory mostly by gas chromatographic-mass spectrometric methods. This study aimed to evaluate a more effective approach to simultaneously quantify these analytes (i.e., amphetamine, methamphetamine, 3,4 methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine (MDMA), morphine, codeine, 6-acetylmorphine, 6-acetylcodeine, ketamine and norketamine) in postmortem urine and blood specimens by liquid chromatography-tandem mass spectrometry (LC-MS-MS). Samples (1 mL) were extracted via solid-phase extraction, evaporated and reconstituted in the mobile phase for injection into the LC-MS-MS system. Respective deuterated analogs of these analytes were used as internal standards. Chromatographic separation was achieved by an Agilent Zorbax SB-Aq analytical column at 50 degrees C. Mass spectrometric analysis was performed by electrospray ionization in positive-ion dynamic multiple reaction monitoring mode with optimized collision energy for respective precursor ion selected for each analyte, and the monitoring of two transition ions. Performance characteristics were assessed using drug-free samples that were fortified with 50 1,000 ng/mL of the 10 analytes. Analytical parameters evaluated and resulting data are as follows: (i) average extraction recoveries (n= 3) were better than 80%, except for MDMA (71%) and morphine (74%); (ii) inter-day and intra-day precision ranges (%CV) were 1.59-8.80% and 0.57-3.89%, respectively; (iii) calibration linearity (r2), detection limit and quantitation limit for all analytes were >0.999, 1 and 5 ng/mL, respectively; (iv) matrix effects (ion suppression) were observed for three analytes, but were satisfactorily compensated for by the deuterated internal standards adopted in the analytical protocol. This method was successfully applied to the analysis of specimens collected from unknown death cases from various district prosecutors' offices in Taiwan, and was also found helpful to understanding whether the detected opiates were derived from heroin or legal morphine/codeine-containing medications. PMID- 28985333 TI - Nonhuman Primate Models of Neurodegenerative Disorders. AB - Alzheimer's (AD), Huntington's (HD), and Parkinson's (PD) disease are age-related neurodegenerative disorders characterized by progressive neuronal cell death. Although each disease has particular pathologies and symptoms, accumulated evidence points to similar mechanisms of neurodegeneration, including inflammation, oxidative stress, and protein aggregation. A significant body of research is ongoing to understand how these pathways affect each other and what ultimately triggers the onset of the disease. Experiments in nonhuman primates (NHPs) account for only 5% of all research in animals. Yet the impact of NHP studies for clinical translation is much greater, especially for neurodegenerative disorders, as NHPs have a complex cognitive and motor functions and highly developed neuroanatomy. New NHP models are emerging to better understand pathology and improve the platform in which to test novel therapies. The goal of this report is to review NHP models of AD, HD, and PD in the context of the current understanding of these diseases and their contribution to the development of novel therapies. PMID- 28985335 TI - Current Concepts in the Treatment of Renovascular Hypertension. AB - Renovascular disease (RVD) remains a major cause of secondary and treatment resistant hypertension. Most cases are related either to fibromuscular or atherosclerotic lesions, but a variety of other causes including arterial dissection, stent occlusion, and embolic disease can produce the same syndrome. Recent studies emphasize the kidney's tolerance to moderate flow reduction during antihypertensive drug therapy and the relative safety of medical therapy to control blood pressure. Several prospective trials in moderate RVD fail to identify major benefits from endovascular revascularization for moderate atherosclerotic disease. However, high-risk and progressive renovascular syndromes are recognized to be relatively refractory to medical therapy only and respond better to combining renal revascularization with ongoing medical therapy. Clinicians caring for complex hypertension should be familiar with pathogenic pathways, imaging techniques, and a rational approach to managing renovascular hypertension in the current era. PMID- 28985336 TI - Two Hospitalizations and One Death After Exposure to Ortho-Fluorofentanyl. AB - Two young males were hospitalized with miosis and respiratory dysfunction after exposure to a white powder obtained from a foreign source by mail. A few days later, one of the males was found dead at his home. A serum sample from one of the hospitalized patients and a blood sample from the deceased contained ortho fluorofentanyl in concentrations of 2.5 and 2.4 ng/mL, respectively. It was concluded that death was caused by ortho-fluorofentanyl. PMID- 28985337 TI - DARS2 protects against neuroinflammation and apoptotic neuronal loss, but is dispensable for myelin producing cells. AB - Although mitochondria are ubiquitous, each mitochondrial disease has surprisingly distinctly different pattern of tissue and organ involvement. Congruently, mutations in genes encoding for different mitochondrial tRNA synthetases result in the development of a very flamboyant group of diseases. Mutations in some of these genes, including aspartyl-tRNA synthetase (DARS2), lead to the onset of a white matter disease-leukoencephalopathy with brainstem and spinal cord involvement, and lactate elevation (LBSL) characterized by progressive spastic ataxia and characteristic leukoencephalopathy signature with multiple long-tract involvements. Puzzled by the white matter disease phenotypes caused by DARS2 deficiency when numerous other mutations in the genes encoding proteins involved in mitochondrial translation have a detrimental effect predominantly on neurons, we generated transgenic mice in which DARS2 was specifically depleted in forebrain-hippocampal neurons or myelin-producing cells. Our results now provide the first evidence that loss of DARS2 in adult neurons leads to strong mitochondrial dysfunction and progressive loss of cells. In contrast, myelin producing cells seem to be resistant to cell death induced by DARS2 depletion despite robust respiratory chain deficiency arguing that LBSL might originate from the primary neuronal and axonal defect. Remarkably, our results also suggest a role for early neuroinflammation in the disease progression, highlighting the possibility for therapeutic interventions of this process. PMID- 28985339 TI - A re-sequencing-based ultra-dense genetic map reveals a gummy stem blight resistance-associated gene in Cucumis melo. AB - The melon (Cucumis melo) genome and genetic maps with hundreds to thousands of single nucleotide polymorphism markers were recently released. However, a high resolution genetic map was lacking. Gummy stem blight (Gsb) is a destructive disease responsible for considerable economic losses during melon production. We herein describe the development of an ultra-dense genetic map consisting of 12,932 recombination bin markers covering 1,818 cM, with an average distance of 0.17 cM between adjacent tags. A comparison of the genetic maps for melon, watermelon, and cucumber revealed chromosome-level syntenic relationships and recombination events among the three Cucurbitaceae species. Our genetic map was useful for re-anchoring the genome scaffolds of melon. More than 92% assembly was anchored to 12 pseudo-chromosomes and 90% of them were oriented. Furthermore, 1,135 recombination hotspots revealed an unbalanced recombination rate across the melon genome. Genetic analyses of the Gsb-resistant and -susceptible lines indicated the resistance phenotype is mediated by a single dominant gene. We identified Gsb-resistance gene candidates in a 108-kb region on pseudo-chromosome 4. Our findings verify the utility of an ultra-dense genetic map for mapping a gene of interest, and for identifying new disease resistant genes. PMID- 28985338 TI - RFamide-related Peptide-3 and the Trade-off between Reproductive and Ingestive Behavior. AB - Ingestive and sex behaviors are important for individual survival and reproductive success, but when environmental energy availability is limited, individuals of many different species make a trade-off, forfeiting sex for ingestive behavior. For example, food-deprived female Syrian hamsters (Mesocricetus auratus) forego vaginal scent marking and lordosis (sex behaviors) in favor of foraging, hoarding, and eating food (ingestive behavior). Reproductive processes tend to be energetically costly, and individual survival requires homeostasis in metabolic energy. Thus, during energetic challenges, the chances of survival are enhanced by decreasing the energy expended on reproductive processes. The entire hypothalamic-pituitary-gonadal (HPG) system is inhibited by severe energetic challenges, but comparatively little is known about the effects of mild energetic challenges. We hypothesized that (1) a trade-off is made between sex and ingestive behavior even when the level of food restriction is insufficient to inhibit the HPG system; (2) mild energetic challenges force a trade-off between appetitive ingestive and sex behaviors, but not consummatory versions of the same behaviors; and (3) the trade-off is orchestrated by ovarian steroid modulation of RFamide-related peptide 3 (RFRP-3). In other species, RFRP 3, an ortholog of avian gonadotropin-inhibitory hormone, is implicated in control of behavior in response to energetic challenges and stressful stimuli. In support of our three hypotheses, there is a "dose-response" effect of food restriction and re-feeding on the activation of RFRP-3-immunoreactive cells in the dorsomedial hypothalamus and on appetitive behaviors (food hoarding and sexual motivation), but not on consummatory behaviors (food intake and lordosis), with no significant effect on circulating levels of estradiol or progesterone. The effect of food restriction on the activation of RFRP-3 cells is modulated at the time of estrus in gonadally-intact females and in ovariectomized females treated with progesterone alone or with estradiol plus progesterone. Intracerebral treatment with RFRP-3 results in significant decreases in sexual motivation and results in significant but small increases in food hoarding in hamsters fed ad libitum. These and other results are consistent with the idea that ovarian steroids and RFRP-3 are part of a system that orchestrates trade-offs in appetitive behaviors in environments where energy availability fluctuates. PMID- 28985340 TI - Genome-wide mapping of large deletions and their population-genetic properties in dairy cattle. AB - Large genomic deletions are potential candidate for loss-of-function, which could be lethal as homozygote. Analysing whole genome data of 175 cattle, we report 8,480 large deletions (199 bp-773 KB) with an overall false discovery rate of 8.8%; 82% of which are novel compared with deletions in the dbVar database. Breakpoint sequence analyses revealed that majority (24 of 29 tested) of the deletions contain microhomology/homology at breakpoint, and therefore, most likely generated by microhomology-mediated end joining. We observed higher differentiation among breeds for deletions in some genic-regions, such as ABCA12, TTC1, VWA3B, TSHR, DST/BPAG1, and CD1D. The genes overlapping deletions are on average evolutionarily less conserved compared with known mouse lethal genes (P value = 2.3 * 10-6). We report 167 natural gene knockouts in cattle that are apparently nonessential as live homozygote individuals are observed. These genes are functionally enriched for immunoglobulin domains, olfactory receptors, and MHC classes (FDR = 2.06 * 10-22, 2.06 * 10-22, 7.01 * 10-6, respectively). We also demonstrate that deletions are enriched for health and fertility related quantitative trait loci (2-and 1.5-fold enrichment, Fisher's P-value = 8.91 * 10 10 and 7.4 * 10-11, respectively). Finally, we identified and confirmed the breakpoint of a ~525 KB deletion on Chr23:12,291,761-12,817,087 (overlapping BTBD9, GLO1 and DNAH8), causing stillbirth in Nordic Red Cattle. PMID- 28985341 TI - Relationship Between Blood Pressure Variability and Cognitive Function in Elderly Patients With Good Blood Pressure Control. AB - BACKGROUND: Although higher blood pressure (BP) levels and BP variability have been associated with cognitive impairment, data are sparse regarding the relationship between BP variability and cognitive function in elderly patients with well BP control. METHODS: We analyzed 232 ambulatory patients with one or more cardiovascular risk factors. All patients underwent ambulatory BP monitoring and the Japanese version of the Montreal Cognitive Assessment (MoCA-J). RESULTS: The mean age was 77.7 +/- 8.3 years; 33.6% were male, and 85.3% were taking antihypertensive drugs. The average 24-hour BP level was 118.7 +/- 10.0/68.3 +/- 6.4 mm Hg. When we divided the weighted SD of systolic BP (SBP) as a measure of BP variability into quartiles, the top quartile group (>=19.6 mm Hg) had a significantly lower total MoCA-J score (15.4 [95% confidence interval 14.2-16.7] vs. 17.9 [17.2-18.6], P = 0.001) and lower scores on several domains, visuoexecutive (2.2 [1.9-2.6] vs. 2.8 [2.6-2.9], P = 0.012), abstraction (1.0 [0.7-1.2] vs. 1.3 [1.1-1.4], P = 0.015), attention (2.8 [2.4-3.1] vs. 3.6 [3.4 3.8], P = 0.001), and naming (2.1 [1.9-2.3] vs. 2.5 [2.4-2.6], P = 0.001) than quartiles 1 through 3 combined, after adjustment for age and 24-hour SBP. These associations were not found in the quartiles of 24-hour SBP. CONCLUSIONS: In elderly patients with well ambulatory BP control, higher BP variability but not average ambulatory BP level was associated with cognitive impairment. PMID- 28985342 TI - The Effect of Head and Neck Radiotherapy on Blood Pressure and Orthostatic Hypotension in Patients With Head and Neck Tumors. AB - BACKGROUND: Radiotherapy (RT) plays a key role in the management of head and neck cancer (HNC), especially in locally advanced disease. Patients undergoing head and neck RT, especially elderly ones, are suffering from low and labile blood pressure (BP) during the treatment. They complain of weakness and fatigue and are prone to recurrent falls. The aim of this study was to characterize BP changes during RT period. METHODS: Patients with HNC, receiving radiation to the neck, were recruited from Sheba medical center RT unit. Office BP, orthostatic measurements, 24-hour ambulatory BP monitoring, body weight, and metabolic parameters were measured at baseline after 30 days and after 90 days from beginning of therapy. RESULTS: Nineteen patients (17 males), 64 +/- 12 years old were recruited. Nine hypertensive patients continued their antihypertensive treatment during the study. Office systolic BP and diastolic BP decreased significantly after 30 days (128 +/- 4/80 +/- 3 to 122 +/- 3/74 +/- 3 mm Hg; P < 0.05). Average 24-hour BP values after 30 days of RT decreased from 130 +/- 3/76 +/- 2 to 123 +/- 3/71 +/- 2 mm Hg; P < 0.05. A similar trend was observed for day and night BP levels. Decrease in office and ambulatory BP was sustained for several months after RT completion. No orthostasis was observed during the study period. Patient lost weight significantly during the study period. However, BP changes were independent of weight loss. CONCLUSION: There is a significant and sustained BP reduction after head and neck RT, without orthostatic changes. Clinicians should be aware of this phenomenon and consider treatment adaption accordingly. PMID- 28985343 TI - Angiotensinergic Innervation of the Human Right Atrium: Implications for Cardiac Reflexes. AB - BACKGROUND: The right atrium is densely innervated and provides sensory input to important cardiocirculatory reflexes controlling cardiac output and blood pressure. Its angiotensin (Ang) II-expressing innervation may release Ang II as a neuropeptide cotransmitter to modulate reflexes but has not yet been characterized. METHODS: Intraoperative surgical biopsies from human right atria (n = 7) were immunocytologically stained for Ang II, tyrosine hydroxylase (TH), and synaptophysin (SYN). Tissue angiotensins were extracted and quantified by radioimmunoassay. RESULTS: Angiotensinergic fibers were frequent in epicardial nerves and around vessels with variable TH co-localization (none to >50%/bundle). Fibers were also widely distributed between cardiomyocytes and in the endocardium where they were typically nonvaricose, TH/SYN-negative and usually accompanied by varicose catecholaminergic fibers. In the endocardium, some showed large varicosities and were partially TH or SYN-positive. A few endocardial regions showed scattered nonvaricose Ang fibers ending directly between endothelial cells. Occasional clusters of thin varicose terminals co-localizing SYN or TH were located underneath, or protruded into, the endothelium. Endocardial density of Ang and TH-positive fibers was 30-300 vs. 200-450/mm2. Atrial Ang II, III, and I concentrations were 67, 16, and 5 fmol/g (median) while Ang IV and V were mostly undetectable. CONCLUSIONS: The human right atrium harbors an abundant angiotensinergic innervation and a novel potential source of atrial Ang II. Most peripheral fibers were noncatecholaminergic afferents or preterminal vagal efferents and a minority was presumably sympathetic. Neuronal Ang II release from these fibers may modulate cardiac and circulatory reflexes independently from plasma and tissue Ang II sources. PMID- 28985344 TI - Point-of-care testing in primary care patients with acute cardiopulmonary symptoms: a systematic review. AB - Background: Point-of-care tests (POCT) can assist general practitioners (GPs) in diagnosing and treating patients with acute cardiopulmonary symptoms, but it is currently unknown if POCT impact relevant clinical outcomes in these patients. Objective: To assess whether using POCT in primary care patients with acute cardiopulmonary symptoms leads to more accurate diagnosis and impacts clinical management. Methods: We performed a systematic review in four bibliographic databases. Articles published before February 2016 were screened by two reviewers. Studies evaluating the effect of GP use of POCT on clinical diagnostic accuracy and/or effect on treatment and referral rate in patients with cardiopulmonary symptoms were included. Results: Our search yielded nine papers describing data from seven studies, on the clinical diagnostic accuracy of POCT in a total of 2277 primary care patients with acute cardiopulmonary symptoms. Four papers showed data on GP use of D-dimer POCT in pulmonary embolism (two studies); two studies on Troponin T in acute coronary syndrome; one on heart-type fatty acid-binding protein (H-FABP) in acute coronary syndrome; one on B-type natriuretic peptide (BNP) in heart failure; one on 3-in-1 POCT (Troponin T, BNP, D-dimer) in acute coronary syndrome, heart failure and/or pulmonary embolism. Only one study assessed the effect of GP use of POCT on treatment initiation and one on actual referral rates. Conclusion: There is currently limited and inconclusive evidence that actual GP use of POCT in primary care patients with acute cardiopulmonary symptoms leads to more accurate diagnosis and affects clinical management. However, some studies show promising results, especially when a POCT is combined with a clinical decision rule. PMID- 28985347 TI - Systemic Angiotensinogen Concentrations Are Independently Associated With Left Ventricular Diastolic Function in a Community Sample. AB - BACKGROUND: Left ventricular (LV) diastolic dysfunction characterizes heart failure with a preserved ejection fraction. Although it is recognized that the renin-angiotensin-aldosterone system (RAAS) decreases LV diastolic function, whether systemic angiotensinogen (AGT) contributes to these effects is uncertain. Hence, the aim was to determine the relationship between systemic AGT concentrations and LV diastolic function. METHODS: LV diastolic function was determined from the mean of the lateral and septal wall myocardial tissue lengthening at the mitral annulus (average e') and from the ratio of early transmitral blood flow velocity (E) to average e' (E/e') in 445 Black African participants from a community sample. RESULTS: In multivariate regression models with adjustments for age, sex, waist circumference diabetes mellitus, alcohol and tobacco use, hypertension treatment, systolic blood pressure (BP), and relative wall thickness, the square root of serum AGT concentrations was independently associated with E/e' (partial r (95% confidence interval [CI]) = 0.11 (0.02 0.21), P = 0.04), but not with average e' (partial r (95% CI) = -0.06 (-0.15 to 0.04), P = 0.25). There was no association between plasma renin concentrations and markers of diastolic function (all P > 0.05). CONCLUSION: Circulating AGT concentrations are associated with LV diastolic function beyond BP and other confounders in an African population. Hence, through circulating AGT, the systemic RAAS may play an important role in contributing to LV diastolic function in Black Africans. PMID- 28985345 TI - Replication stress-induced endogenous DNA damage drives cellular senescence induced by a sub-lethal oxidative stress. AB - Although oxidative stress has been shown to induce senescence and replication stress independently, no study has implicated unresolved replication stress as the driver for cellular senescence in response to oxidative stress. Using cells exposed to increasing concentrations of hydrogen peroxide, we show that sub lethal amount of exogenous hydrogen peroxide induces two waves of DNA damage. The first wave is rapid and transient while the second wave coincides with the cells transition from the S to the G2/M phases of cell cycle. Subsequently, cells enter growth arrest accompanied by the acquisition of senescence-associated characteristics. Furthermore, a p53-dependent decrease in Rad51, which is associated with the formation of DNA segments with chromatin alterations reinforcing senescence, and Lamin B1 that is involved in chromatin remodeling, is observed during the establishment of the senescent phenotype. On the other hand, increase in senescence associated-beta-Gal activity, a classical marker of senescence and HMGA2, a marker of the senescence-associated heterochromatin foci, is shown to be independent of p53. Together, our findings implicate replication stress-induced endogenous DNA damage as the driver for the establishment of cellular senescence upon sub-lethal oxidative stress, and implicate the role of p53 in some but not all hallmarks of the senescent phenotype. PMID- 28985348 TI - Elbow Room for Best Practice? Montgomery, Patients' values, and Balanced Decision Making in Person-Centred Clinical Care. AB - The UK Supreme Court Montgomery judgment marks a decisive shift in the legal test of duty of care in the context of consent to treatment, from the perspective of the clinician (as represented by Bolam rules) to that of the patient. A majority of commentators on Montgomery have focused on the implications of the judgment for disclosure of risk. In this article, we set risk disclosure in context with three further elements of the judgment: benefits, options, and dialogue. These elements, we argue, taken together with risk disclosure, reflect the origins of the Montgomery ruling in a model of consent based on autonomy of patient choice through shared decision-making with their doctor. This model reflects recent developments in both law and medicine and is widely regarded (by the General Medical Council and others) as representing best practice in contemporary person centred medicine. So understood, we suggest, the shift marked by Montgomery in the basis of duty of care is a shift in underpinning values: it is a shift from the clinician's interpretation about what would be best for patients to the values of (to what is significant or matters from the perspective of) the particular patient concerned in the decision in question. But the values of the particular patient do not thereby become paramount. The Montgomery test of duty of care requires the values of the particular patient to be balanced alongside the values of a reasonable person in the patient's position. We illustrate some of the practical challenges arising from the balance of considerations required by Montgomery with examples from surgical care. These examples show the extent to which Montgomery, in mirroring the realities of clinical decision-making, provides elbowroom for best practice in person-centred clinical care. PMID- 28985349 TI - Concomitant Hypertension and Diabetes: Role of Aortic Stiffness and Glycemic Management. PMID- 28985350 TI - Cousins, Genetic Diagnosis and Liability of Clinicians: Smith & Another V University of Leicester NHS Trust [2016] EWHC 817 (QB). AB - This comment analyses the recent High Court decision in Smith & Another v University of Leicester NHS Trust. In this case, the court struck out a claim brought by a patient's second cousins regarding their failure to provide the patient with an accurate diagnosis, which would have resulted in the claimants being diagnosed with hereditary disease earlier than they in fact were. The claimants argued that the doctors' failure to conduct the test caused harm and a duty of care was owed in respect of the patient's relatives. The defendant conceded the issue of foreseeable harm but argued a duty was not fair, just, and reasonable when treating the patient and no other, or, alternately, if the duty was to inform then the cousins was insufficiently proximate. It is argued in this comment that the judge was correct to reject the claim but that aspects of the judgment demanded greater analysis. PMID- 28985346 TI - Single-molecule kinetic analysis of HP1-chromatin binding reveals a dynamic network of histone modification and DNA interactions. AB - Chromatin recruitment of effector proteins involved in gene regulation depends on multivalent interaction with histone post-translational modifications (PTMs) and structural features of the chromatin fiber. Due to the complex interactions involved, it is currently not understood how effectors dynamically sample the chromatin landscape. Here, we dissect the dynamic chromatin interactions of a family of multivalent effectors, heterochromatin protein 1 (HP1) proteins, using single-molecule fluorescence imaging and computational modeling. We show that the three human HP1 isoforms are recruited and retained on chromatin by a dynamic exchange between histone PTM and DNA bound states. These interactions depend on local chromatin structure, the HP1 isoforms as well as on PTMs on HP1 itself. Of the HP1 isoforms, HP1alpha exhibits the longest residence times and fastest binding rates due to DNA interactions in addition to PTM binding. HP1alpha phosphorylation further increases chromatin retention through strengthening of multivalency while reducing DNA binding. As DNA binding in combination with specific PTM recognition is found in many chromatin effectors, we propose a general dynamic capture mechanism for effector recruitment. Multiple weak protein and DNA interactions result in a multivalent interaction network that targets effectors to a specific chromatin modification state, where their activity is required. PMID- 28985351 TI - Non-prescription medicine misuse, abuse and dependence: a cross-sectional survey of the UK general population. PMID- 28985352 TI - Associations between mental distress and physical activity in US adults: a dose response analysis BRFSS 2011. AB - Background: To examine the associations between levels of severity of mental distress (MD) and meeting the 2008 physical activity (PA) recommendations using the MD Severity Index (MDSI). Methods: Participants (n = 431 313) were adults (>=18 years of age) who responded to the 2011 Behavioral Risk Factor Surveillance System (BRFSS). MD was categorized into five levels of severity: 0-4, 5-10, 11 16, 17-22 and >=23 days/month. The dependent variable was self-reported PA volume of at least 150 min/wk (or vigorous equivalent, 75 min/wk). Results: Following adjustment for age, gender, race/ethnicity, education and body mass index, the odds of reporting meeting the PA recommendations were significantly lower among those reporting the following days per month of MD: 5-10 (odds ratio [OR] = 0.92, 95% confidence interval [CI]: 0.87-0.96), 11-16 (OR = 0.76, 95% CI: 0.71-0.82), 17-22 (OR = 0.69, 95% CI: 0.62-0.76) and >=23 (OR = 0.64, 95% CI: 0.60-0.67). An inverse dose-response (P < 0.01) was observed between the severity of MD and meeting the current PA recommendations. Conclusions: An inverse dose-response relationship was found between the severity of MD and volumes of PA meeting the 2008 recommendation. These findings lend support for the epidemiological utility of the MDSI when examining the relationship between MD and PA. PMID- 28985353 TI - Loss of ADAMTS3 activity causes Hennekam lymphangiectasia-lymphedema syndrome 3. AB - Primary lymphedema is due to developmental and/or functional defects in the lymphatic system. It may affect any part of the body, with predominance for the lower extremities. Twenty-seven genes have already been linked to primary lymphedema, either isolated, or as part of a syndrome. The proteins that they encode are involved in VEGFR3 receptor signaling. They account for about one third of all primary lymphedema cases, underscoring the existence of additional genetic factors. We used whole-exome sequencing to investigate the underlying cause in a non-consanguineous family with two children affected by lymphedema, lymphangiectasia and distinct facial features. We discovered bi-allelic missense mutations in ADAMTS3. Both were predicted to be highly damaging. These amino acid substitutions affect well-conserved residues in the prodomain and in the peptidase domain of ADAMTS3. In vitro, the mutant proteins were abnormally processed and sequestered within cells, which abolished proteolytic activation of pro-VEGFC. VEGFC processing is also affected by CCBE1 mutations that cause the Hennekam lymphangiectasia-lymphedema syndrome syndrome type1. Our data identifies ADAMTS3 as a novel gene that can be mutated in individuals affected by the Hennekam syndrome. These patients have distinctive facial features similar to those with mutations in CCBE1. Our results corroborate the recent in vitro and murine data that suggest a close functional interaction between ADAMTS3 and CCBE1 in triggering VEGFR3 signaling, a cornerstone for the differentiation and function of lymphatic endothelial cells. PMID- 28985354 TI - State-level income inequality and meeting physical activity guidelines; differential associations among US men and women. AB - Background: Previous work has identified a relationship between income inequality and risk for obesity and heart attack. We investigated the relationship between state-level income inequality and physical activity among US adults. Methods: We used Behavioral Risk Factor Surveillance System (BRFSS) cross-sectional data from a population based and representative sample of n = 428 828 US adults. Multilevel models were used to determine the association between state-level income inequality and participation in physical activity and strengthening exercises in the previous month. Results: In comparison to males, females were significantly more likely to report being physically inactive (OR = 1.07, 95% CI = 1.04, 1.11), and less likely to meet aerobic activity requirements (OR = 0.90, 95% CI = 0.88, 0.93), meet strengthening activities (OR = 0.71, 95% CI = 0.69, 0.74), and meet overall physical activity recommendations (OR = 0.91, 95% CI = 0.88, 0.94). Cross level Gini * sex interactions indicated that income inequality was associated with increased odds for participating in no physical activity (OR = 1.08, 95% CI = 1.05, 1.12), decreased odds in participating in strengthening physical activity (OR = 0.92, 95% CI = 0.89, 0.96), aerobic activity (OR = 0.96, 95% CI = 0.93, 0.99), and in meeting overall physical activity recommendations (OR = 0.93, 95% CI = 0.91, 0.95) among women only. Conclusions: Future studies are needed to identify mechanisms in which income inequality leads to physical activity behavior among US women. PMID- 28985355 TI - Master or apprentice: rethinking entry points and training in Public Health. AB - Background: The Public Health workforce needs to adapt to a policy environment in which the need to improve public health is not only a key challenge but also has to be delivered within financial constraints. Methods: A total of 14 qualitative individual interviews or focus groups (of up to 10 people), were conducted with senior Public Health staff in 12 local authorities and in Public Health England in the Yorkshire and the Humber region of England. Thematic analysis was applied to the transcribed interviews. Results: Despite cuts in training budgets, junior staff were increasingly expected to deliver Public Health functions. There is also an absence of a career ladder for this core Public Health workforce. There were concerns that financial constraints would lead to reductions in Public Health skills with fewer staff to provide critical analysis. Formal qualifications were increasingly less valued. Instead staff were expected to have a broader skill set with an emphasis on experience. Entry points into Public Health careers need rethinking. There was an expectation that Public Health departments would 'grow their own'. Conclusions: Apprenticeship schemes could help maintain or enhance the professional status of Public Health and provide a training route for Public Health practitioners. PMID- 28985356 TI - Multiple hybrid de novo genome assembly of finger millet, an orphan allotetraploid crop. AB - Finger millet (Eleusine coracana (L.) Gaertn) is an important crop for food security because of its tolerance to drought, which is expected to be exacerbated by global climate changes. Nevertheless, it is often classified as an orphan/underutilized crop because of the paucity of scientific attention. Among several small millets, finger millet is considered as an excellent source of essential nutrient elements, such as iron and zinc; hence, it has potential as an alternate coarse cereal. However, high-quality genome sequence data of finger millet are currently not available. One of the major problems encountered in the genome assembly of this species was its polyploidy, which hampers genome assembly compared with a diploid genome. To overcome this problem, we sequenced its genome using diverse technologies with sufficient coverage and assembled it via a novel multiple hybrid assembly workflow that combines next-generation with single molecule sequencing, followed by whole-genome optical mapping using the Bionano Irys(r) system. The total number of scaffolds was 1,897 with an N50 length >2.6 Mb and detection of 96% of the universal single-copy orthologs. The majority of the homeologs were assembled separately. This indicates that the proposed workflow is applicable to the assembly of other allotetraploid genomes. PMID- 28985357 TI - CRISPR-Cas9-mediated functional dissection of 3'-UTRs. AB - Many studies using reporter assays have demonstrated that 3' untranslated regions (3'-UTRs) regulate gene expression by controlling mRNA stability and translation. Due to intrinsic limitations of heterologous reporter assays, we sought to develop a gene editing approach to investigate the regulatory activity of 3'-UTRs in their native context. We initially used dual-CRISPR (clustered, regularly interspaced, short palindromic repeats)-Cas9 targeting to delete DNA regions corresponding to nine chemokine 3'-UTRs that destabilized mRNA in a reporter assay. Targeting six chemokine 3'-UTRs increased chemokine mRNA levels as expected. However, targeting CXCL1, CXCL6 and CXCL8 3'-UTRs unexpectedly led to substantial mRNA decreases. Metabolic labeling assays showed that targeting these three 3'-UTRs increased mRNA stability, as predicted by the reporter assay, while also markedly decreasing transcription, demonstrating an unexpected role for 3' UTR sequences in transcriptional regulation. We further show that CRISPR-Cas9 targeting of specific 3'-UTR elements can be used for modulating gene expression and for highly parallel localization of active 3'-UTR elements in the native context. Our work demonstrates the duality and complexity of 3'-UTR sequences in regulation of gene expression and provides a useful approach for modulating gene expression and for functional annotation of 3'-UTRs in the native context. PMID- 28985358 TI - Identification of Plagl1/Zac1 binding sites and target genes establishes its role in the regulation of extracellular matrix genes and the imprinted gene network. AB - PLAGL1/ZAC1 undergoes parental genomic imprinting, is paternally expressed, and is a member of the imprinted gene network (IGN). It encodes a zinc finger transcription factor with anti-proliferative activity and is a candidate tumor suppressor gene on 6q24 whose expression is frequently lost in various neoplasms. Conversely, gain of PLAGL1 function is responsible for transient neonatal diabetes mellitus, a rare genetic disease that results from defective pancreas development. In the present work, we showed that Plagl1 up-regulation was not associated with DNA damage-induced cell cycle arrest. It was rather associated with physiological cell cycle exit that occurred with contact inhibition, growth factor withdrawal, or cell differentiation. To gain insights into Plagl1 mechanism of action, we identified Plagl1 target genes by combining chromatin immunoprecipitation and genome-wide transcriptomics in transfected cell lines. Plagl1-elicited gene regulation correlated with multiple binding to the proximal promoter region through a GC-rich motif. Plagl1 target genes included numerous genes involved in signaling, cell adhesion, and extracellular matrix composition, including collagens. Plagl1 targets also included 22% of the 409 genes that make up the IGN. Altogether, this work identified Plagl1 as a transcription factor that coordinated the regulation of a subset of IGN genes and controlled extracellular matrix composition. PMID- 28985359 TI - PARP1 controls KLF4-mediated telomerase expression in stem cells and cancer cells. AB - Telomerase is highly expressed in cancer and embryonic stem cells (ESCs) and implicated in controlling genome integrity, cancer formation and stemness. Previous studies identified that Kruppel-like transcription factor 4 (KLF4) activates telomerase reverse transcriptase (TERT) expression and contributes to the maintenance of self-renewal in ESCs. However, little is known about how KLF4 regulates TERT expression. Here, we discover poly(ADP-ribose) polymerase 1 (PARP1) as a novel KLF4-interacting partner. Knockdown of PARP1 reduces TERT expression and telomerase activity not only in cancer cells, but also in human and mouse ESCs. Recruitment of KLF4 to TERT promoter is reduced in PARP1 suppressed cells. The poly(ADP-ribose) polymerase activity is dispensable, while the oligo(ADP-ribose) polymerase activity is required for the PARP1- and KLF4 mediated TERT activation. Repression of Parp1 in mouse ESCs decreases expression of pluripotent markers and induces differentiation. These results suggest that PARP1 recruits KLF4 to activate telomerase expression and stem cell pluripotency, indicating a positive regulatory role of the PARP1-KLF4 complex in telomerase expression in cancer and stem cells. PMID- 28985360 TI - Tandem phage-display for the identification of non-overlapping binding pairs of recombinant affinity reagents. AB - The 'sandwich' binding format, which uses two reagents that can bind simultaneously to a given analyte, is the gold standard in diagnostics and many biochemical techniques. One of the bottlenecks in creating a sandwich assay is identifying pairs of reagents that bind non-competitively to the target. To bridge this gap, we invented Megaprimer Shuffling for Tandem Affinity Reagents (MegaSTAR) to identify non-competitive binding pairs of recombinant affinity reagents through phage-display. The key innovation in MegaSTAR is the construction of a tandem library, in which two reagents are randomly-displayed on the phage surface. This is accomplished by using a pool of 300-nucleotide long 'megaprimers', which code for previously-selected reagents, to prime second strand synthesis of a single-stranded DNA template and generate millions of pair wise combinations. The tandem library is then affinity selected to isolate pairs that both reagents contribute to binding the target. As a proof-of-concept, we used MegaSTAR to identify pairs of fibronectin type III monobodies for three human proteins. For each target, we could identify between five and fifteen unique pairs and successfully used a single pair in a sandwich assay. MegaSTAR is a versatile tool for generating sandwich ELISA-grade and bispecific reagents. PMID- 28985361 TI - Novel cell surface luciferase reporter for high-throughput yeast one-hybrid screens. AB - Gene-centered yeast one-hybrid (Y1H) screens provide a powerful and effective strategy to identify transcription factor (TF)-promoter interactions. While genome-wide TF ORFeome clone collections are increasingly available, screening protocols have limitations inherent to the properties of the enzymatic reaction used to identify interactions and to the procedure required to perform the assay in a high-throughput format. Here, we present the development and validation of a streamlined strategy for quantitative and fully automated gene-centered Y1H screens using a novel cell surface Gaussia luciferase reporter. PMID- 28985362 TI - Combatting the opioid epidemic: Baltimore's experience and lessons learned. AB - In the midst of a national opioid crisis, Baltimore City witnessed 393 deaths from drug and alcohol overdose in 2015. With an estimated 25 000 residents who are addicted to heroin or other opioids, Baltimore has been profoundly affected by the opioid epidemic. Other resources have commented on federal, state-based, and provider responses to the opioid crisis. This article examines what may be done at the city level based on the experiences of the Baltimore City Health Department. Local jurisdictions must play a critical role in addressing the U.S. opioid crisis through public health coalitions, overdose prevention, treatment expansion, and anti-stigma education. PMID- 28985363 TI - Protein phosphatase 1 and phosphatase 1 nuclear targeting subunit-dependent regulation of DNA-dependent protein kinase and non-homologous end joining. AB - DNA-dependent protein kinase catalytic subunit (DNA-PKcs) plays a key role in mediating non-homologous end joining (NHEJ), a major repair pathway for DNA double-strand breaks (DSBs). The activation, function and dynamics of DNA-PKcs is regulated largely by its reversible phosphorylation at numerous residues, many of which are targeted by DNA-PKcs itself. Interestingly, these DNA-PKcs phosphorylation sites function in a distinct, and sometimes opposing manner, suggesting that they are differentially regulated via complex actions of both kinases and phosphatases. In this study we identified several phosphatase subunits as potential DSB-associated proteins. In particular, protein phosphatase 1 (PP1) is recruited to a DSB-mimicking substrate in Xenopus egg extracts and sites of laser microirradiation in human cells. Depletion of PP1 impairs NHEJ in both Xenopus egg extracts and human cells. PP1 binds multiple motifs of DNA-PKcs, regulates DNA-PKcs phosphorylation, and is required for DNA-PKcs activation after DNA damage. Interestingly, phosphatase 1 nuclear targeting subunit (PNUTS), an inhibitory regulator of PP1, is also recruited to DNA damage sites to promote NHEJ. PNUTS associates with the DNA-PK complex and is required for DNA-PKcs phosphorylation at Ser-2056 and Thr-2609. Thus, PNUTS and PP1 together fine-tune the dynamic phosphorylation of DNA-PKcs after DNA damage to mediate NHEJ. PMID- 28985364 TI - Concomitant pulmonologist and primary care for chronic obstructive pulmonary disease: a population study. AB - Background: Pulmonologists provide quality care, however, their number is not adequate to take care of all the chronic obstructive pulmonary disease (COPD) needs of the population and their services come with a cost. Their optimal role should be defined, ideally based on evidence, to ensure that their abilities are applied most efficiently where needed. Objective: To determine if concomitant pulmonologist and primary care physician care after COPD hospital or emergency department discharge was associated with better health outcomes than primary care services alone. Methods: A population cohort study was conducted in Ontario, Canada from 2004 to 2011. All individuals with a COPD hospital or emergency department discharge were included. Patients who visited both a pulmonologist and a primary care physician within 30 days of the index discharge were matched to patients who had visited a primary care physician alone using propensity scores. The composite outcome of death, COPD hospitalization or COPD emergency department visit was compared using proportional hazards regression. Results: In the propensity score matched sample, 39.7% of patients who received concomitant care and 38.9% who received primary care only died or visited the emergency department visit or hospital for COPD within 1 year (adjusted hazard ratio 1.08, 95% confidence interval 1.00-1.17). The former, however, were more likely to receive diagnostic testing and medications. Conclusion: Patients who received concomitant care after COPD emergency department or hospital discharge did not have better outcomes than those who received primary care alone, however, they did receive more testing and medical management. PMID- 28985365 TI - Zebrafish cdc6 hypomorphic mutation causes Meier-Gorlin syndrome-like phenotype. AB - Cell Division Cycle 6 (Cdc6) is a component of pre-replicative complex (preRC) forming on DNA replication origins in eukaryotes. Recessive mutations in ORC1, ORC4, ORC6, CDT1 or CDC6 of the preRC in human cause Meier-Gorlin syndrome (MGS) that is characterized by impaired post-natal growth, short stature and microcephaly. However, vertebrate models of MGS have not been reported. Through N ethyl-N-nitrosourea mutagenesis and Cas9 knockout, we generate several cdc6 mutant lines in zebrafish. Loss-of-function mutations of cdc6, as manifested by cdc6tsu4305 and cdc6tsu7cd mutants, lead to embryonic lethality due to cell cycle arrest at the S phase and extensive apoptosis. Embryos homozygous for a cdc6 hypomorphic mutation, cdc6tsu21cd, develop normally during embryogenesis. Later on, compared with their wild-type (WT) siblings, cdc6tsu21cd mutant fish show growth retardation, and their body weight and length in adulthood are greatly reduced, which resemble human MGS. Surprisingly, cdc6tsu21cd mutant fish become males with a short life and fail to mate with WT females, suggesting defective reproduction. Overexpression of Cdc6 mutant forms, which mimic human CDC6(T323R) mutation found in a MGS patient, in zebrafish cdc6tsu4305 mutant embryos partially represses cell death phenotype, suggesting that the human CDC6(T323R) mutation is a hypomorph. cdc6tsu21cd mutant fish will be useful to detect more tissue defects and develop medical treatment strategies for MGS patients. PMID- 28985366 TI - Different hydraulic traits of woody plants from tropical forests with contrasting soil water availability. AB - In southwestern China, tropical karst forests (KF) and non-karst rain forests (NKF) have different species composition and forest structure owing to contrasting soil water availability, but with a few species that occur in both forests. Plant hydraulic traits are important for understanding the species' distribution patterns in these two forest types, but related studies are rare. In this study, we investigated hydraulic conductivity, vulnerability to drought induced cavitation and wood anatomy of 23 abundant and typical woody species from a KF and a neighboring NKF, as well as two Bauhinia liana species common to both forests. We found that the KF species tended to have higher sapwood density, smaller vessel diameter, lower specific hydraulic conductivity (ks) and leaf to sapwood area ratio, and were more resistant to cavitation than NKF species. Across the 23 species distinctly occurring in either KF or NKF, there was a significant tradeoff between hydraulic efficiency and safety, which might be an underlying mechanism for distributions of these species across the two forests. Interestingly, by possessing rather large and long vessels, the two Bauhinia liana species had extremely high ks but were also high resistance to cavitation (escaping hydraulic tradeoff). This might be partially due to their distinctly dimorphic vessels, but contribute to their wide occurrence in both forests. PMID- 28985368 TI - Exploring the impact and use of patients' feedback about their care experiences in general practice settings-a realist synthesis. AB - Background: Policy encourages health care providers to listen and respond to feedback from patients, expecting that it will enhance care experiences. Enhancement of patients' experiences may not yet be a reality, particularly in primary health care settings. Objective: To identify the issues that influence the use and impact of feedback in this context. Design and Setting: A realist synthesis of studies of the use of patient feedback within primary health care settings. Methods: Structured review of published studies between 1971 and January 2015. Results: Eighteen studies were reported in 20 papers. Eleven studies reported patient survey scores as a primary outcome. There is little evidence that formal patient feedback led to enhanced experiences. The likelihood of patient feedback to health care staff stimulating improvements in future patients' experiences appears to be influenced predominantly by staff perceptions of the purpose of such feedback; the validity and type of data that is collected; and where, when and how it is presented to primary health care teams or practitioners and teams' capacity to change. Conclusions: There is limited research into how patient feedback has been used in primary health care practices or its usefulness as a stimulant to improve health care experience. Using a realist synthesis approach, we have identified a number of contextual and intervention-related factors that appear to influence the likelihood that practitioners will listen to, act on and achieve improvements in patient experience. Consideration of these may support research and improvement work in this area. PMID- 28985367 TI - The Novel Evolution of the Sperm Whale Genome. AB - The sperm whale, made famous by Moby Dick, is one of the most fascinating of all ocean-dwelling species given their unique life history, novel physiological adaptations to hunting squid at extreme ocean depths, and their position as one of the earliest branching toothed whales (Odontoceti). We assembled the sperm whale (Physeter macrocephalus) genome and resequenced individuals from multiple ocean basins to identify new candidate genes for adaptation to an aquatic environment and infer demographic history. Genes crucial for skin integrity appeared to be particularly important in both the sperm whale and other cetaceans. We also find sperm whales experienced a steep population decline during the early Pleistocene epoch. These genomic data add new comparative insight into the evolution of whales. PMID- 28985369 TI - Reducing early career general practitioners' antibiotic prescribing for respiratory tract infections: a pragmatic prospective non-randomised controlled trial. AB - Background: Inappropriate antibiotic prescription and consequent antibacterial resistance is a major threat to healthcare. Objectives: To evaluate the efficacy of a multifaceted intervention in reducing early career general practitioners' (GPs') antibiotic prescribing for upper respiratory tract infections (URTIs) and acute bronchitis/bronchiolitis. Methods: A pragmatic non-randomized trial employing a non-equivalent control group design nested within an existing cohort study of GP registrars' (trainees') clinical practice. The intervention included access to online modules (covering the rationale of current clinical guidelines recommending non-prescription of antibiotics for URTI and bronchitis/bronchiolitis, and communication skills in management of acute bronchitis) followed by a face-to-face educational session. The intervention was delivered to registrars (and their supervisors) in two of Australia's seventeen regional GP training providers (RTPs). Three other RTPs were the control group. Outcomes were proportion of registrars' URTI consultations and bronchitis/bronchiolitis consultations prescribed antibiotics. Intention-to-treat analyses employed logistic regression within a Generalised Estimating Equation framework, adjusted for relevant independent variables. The predictors of interest were time; treatment group; and an interaction term for time-by treatment group. The P value associated with an interaction term determined statistically significant differences in antibiotic prescribing. Results: Analyses include data of 217 intervention RTPs' and 311 control RTPs' registrars. There was no significant reduction in antibiotic prescribing for URTIs. For bronchitis/bronchiolitis, a significant reduction (interaction P value = 0.024) remained true for analysis adjusted for independent variables (P value = 0.040). The adjusted absolute reduction in prescribing was 15.8% (95% CI: 4.2%-27.5%). Conclusions: A multifaceted intervention reduced antibiotic prescribing for bronchitis/bronchiolitis but not URTIs. PMID- 28985370 TI - Maintained effect of a training program on attitudes towards depression in family physicians. AB - Background: Family doctors' (FD) attitudes likely play an important role in the recognition and management of depression. Objective: The purpose of the study was to prospectively analyse the short-term and long-term impact of a specifically designed training program on attitudes towards depression among FDs. Methods: A prospective, educational intervention, single group pre- and post-test study with three assessments (pre, post, and 6-month follow-up) was conducted. Participants included 1322 certified FDs who had enrolled voluntarily in a structured postgraduate training in depression. This course was mainly practical and guided by case reports and real clinical experiences. The course was based on Patient's Unmet Needs and Doctors Educational Needs (PUNS & DENS) methodology. Primary outcome was assessed through the Depression Attitudes Questionnaire (DAQ). In total, 970 subjects completed the pre-post assessments, and 787 also completed the 6-month follow-up. Results: After training, FDs positively changed their attitudes towards the management of depression. A significant change was observed in 18 of 20 items of the DAQ. The distinction between unhappiness and depression was initially found to be difficult in 41% of FDs. After the course, the percentage was reduced to 27%. Agreement with the statement that 'psychotherapy is an exclusive practice of specialists' strikingly changed from 57% to 23%. Minimal differences were noted between the post-training assessment and the 6 month follow-up. Conclusions: Attitudes towards depression in FDs can be modified by a structured training program, and this change is maintained over the long term. A short training in psychotherapy (cognitive-behavioural, problem-solving based and psycho-educative oriented) significantly increases the confidence of FDs in treating depression. PMID- 28985372 TI - Evaluation of the Activity of Gamma-Emitting Natural Radionuclides in Seafood and Estimation of the Annual Effective Dose for Different Age Groups in KSA. AB - Twenty-six brands of canned tuna and sardines imported from several countries in Southeast Asia to consume in the KSA. All samples were prepared and analyzed by using a High Pure Germanium Detector of 40% efficiency. Natural radionuclides 40K, 238U (226Ra) and 232Th(228Ra) series were observed with a varying range in all analyzed samples. The values found to be 192.3 +/- 14.6, 1.5 +/- 0.8 and 1.0 +/- 0.6 Bq kg-1 for canned tuna and 219.8 +/- 15.8, 0.37 +/- 0.3 and 1.2 +/- 0.3 Bq kg-1 for canned sardines, respectively. Cesium-137 was not detected at any sample. The comparison between the average activity concentrations of 40K, 238U(226Ra) and 232Th(228Ra) in both canned tuna and sardines was performed and discussed. The dose assessment due to consume/ingestion of seafood was calculated and observed that the calculated committed effective dose is within the global internal dose (290 MUSv/y). PMID- 28985371 TI - The Preoptic Area and the RFamide-Related Peptide Neuronal System Gate Seasonal Changes in Chemosensory Processing. AB - Males of many species rely on chemosensory information for social communication. In male Syrian hamsters (Mesocricetus auratus), as in many species, female chemosignals potently stimulate sexual behavior and a concurrent, rapid increase in circulating luteinizing hormone (LH) and testosterone (T). However, under winter-like, short-day (SD) photoperiods, when Syrian hamsters are reproductively quiescent, these same female chemosignals fail to elicit behavioral or hormonal responses, even after T replacement. It is currently unknown where in the brain chemosensory processing is gated in a seasonally dependent manner such that reproductive responses are only displayed during the appropriate breeding season. The goal of the present study was to determine where this gating occurred by identifying neural loci that respond differentially to female chemosignals across photoperiods, independent of circulating T concentrations. Adult male Syrian hamsters were housed under either long-day (LD) (reproductively active) or SD (reproductively inactive) photoperiods with half of the SD animals receiving T replacement. Animals were exposed to either female hamster vaginal secretions (FHVSs) diluted in mineral oil or to vehicle, and the activational state of chemosensory processing centers and elements of the neuroendocrine reproductive axis were examined. Components of the chemosensory pathway upstream of hypothalamic centers increased expression of FOS, an indirect marker of neuronal activation, similarly across photoperiods. In contrast, the preoptic area (POA) of the hypothalamus responded to FHVS only in LD animals, consistent with its role in promoting expression of male sexual behavior. Within the neuroendocrine axis, the RF-amide related peptide (RFRP), but not the kisspeptin neuronal system responded to FHVS only in LD animals. Neither response within the POA or the RFRP neuronal system was rescued by T replacement in SD animals, mirroring photoperiodic regulation of reproductive responses. Considering the POA and the RFRP neuronal system promote reproductive behavior and function in male Syrian hamsters, differential activation of these systems represents a potential means by which photoperiod limits expression of reproduction to the appropriate environmental context. PMID- 28985374 TI - AD-HOC INTERCOMPARISON OF FOUR DIFFERENT RADON EXHALATION MEASUREMENT METHODS. AB - It is indicated that the exposure to radon originating from the building materials is not negligible and the radon exhalation measurement should get more attention in the future. The experience with four different methods of the exhalation measurement, established in our laboratory for the purpose of the intercomparison is reported. Additionally, a comparison of advantages and disadvantages of used methods is discussed. PMID- 28985373 TI - Pleasure attainment or self-realization: the balance between two forms of well beings are encoded in default mode network. AB - What is a good life and how it can be achieved is one of the fundamental issues. When considering a good life, there is a division between hedonic (pleasure attainment) and eudaimonic well-being (meaning pursuing and self-realization). However, an integrated approach that can compare the brain functional and structural differences of these two forms of well-being is lacking. Here, we investigated how the individual tendency to eudaimonic well-being relative to hedonic well-being, measured using eudaimonic and hedonic balance (EHB) index, is reflected in the functional and structural features of a key network of well being-the default mode network (DMN). We found that EHB was positively correlated with functional connectivity of bilateral ventral medial prefrontal cortex within anterior DMN and bilateral precuneus within posterior DMN. Brain morphometric analysis showed that EHB was also positively correlated with gray matter volume in left precuneus. These results demonstrated that the relative dominance of one form of well-being to the other is reflected in the morphometric characteristics and intrinsic functions of DMN. PMID- 28985376 TI - The impact of economic downturns and budget cuts on homelessness claim rates across 323 local authorities in England, 2004-12. PMID- 28985375 TI - Rapid monoterpene induction promotes the susceptibility of a novel host pine to mountain pine beetle colonization but not to beetle-vectored fungi. AB - Chemical induction can drive tree susceptibility to and host range expansions of attacking insects and fungi. Recently, mountain pine beetle (Dendroctonus ponderosae Hopkins; MPB) has expanded its host range from its historic host lodgepole pine (Pinus contorta var. latifolia Douglas ex Loudon) to jack pine (Pinus banksiana Lamb) in western Canada. Beetle success in jack pine forests likely depends upon the suitability of tree chemistry to MPB and its symbiotic phytopathogenic fungi. In particular, how rapid induced defenses of jack pine affect MPB colonization and the beetle's symbionts is unknown. In the field, we characterized and compared differences in rapid induced phloem monoterpenes between lodgepole and jack pines in response to various densities of Grosmannia clavigera (Robinson-Jeffery and Davidson)-a MPB symbiotic fungus used to simulate beetle attack-inoculations. Overall, lodgepole pine had higher limonene and myrcene, but lower alpha-pinene, concentrations than jack pine. However, myrcene concentrations in jack pine increased with inoculation density, while that in lodgepole pine did not respond to density treatments. We compared the growth and reproduction of MPB's symbiotic fungi, G. clavigera, Ophiostoma montium (Rumford) von Arx and Leptographium longiclavatum Lee, Kim and Breuil, grown on media amended with myrcene, alpha-pinene and limonene at concentrations reflecting two induction levels from each pine species. Myrcene and alpha-pinene amendments inhibited the growth but stimulated the reproduction of G. clavigera, whereas limonene stimulated its growth while inhibiting its reproduction. However, the growth and reproduction of the other fungi were generally stimulated by monoterpene amendments. Overall, our results suggest that jack pine rapid induction could promote MPB aggregation due to high levels of alpha-pinene (pheromone precursor), a positive feedback of myrcene (pheromone synergist) and low levels of limonene (resistance). Jack pine is likely as susceptible to MPB vectored fungi as lodgepole pine, indicating that jack pine induction will likely not adversely affect symbiont activities enough to inhibit the invasion of MPB into jack pine forests. PMID- 28985377 TI - Coping with gravity: the foliar water relations of giant sequoia. AB - In tall trees, the mechanisms by which foliage maintains sufficient turgor pressure and water content against height-related constraints remain poorly understood. Pressure-volume curves generated from leafy shoots collected crown wide from 12 large Sequoiadendron giganteum (Lindley) J. Buchholz (giant sequoia) trees provided mechanistic insights into how the components of water potential vary with height in tree and over time. The turgor loss point (TLP) decreased with height at a rate indistinguishable from the gravitational potential gradient and was controlled by changes in tissue osmotica. For all measured shoots, total relative water content at the TLP remained above 75%. This high value has been suggested to help leaves avoid precipitous declines in leaf-level physiological function, and in giant sequoia was controlled by both tissue elasticity and the balance of water between apoplasm and symplasm. Hydraulic capacitance decreased only slightly with height, but importantly this parameter was nearly double in value to that reported for other tree species. Total water storage capacity also decreased with height, but this trend essentially disappeared when considering only water available within the typical range of water potentials experienced by giant sequoia. From summer to fall measurement periods we did not observe osmotic adjustment that would depress the TLP. Instead we observed a proportional shift of water into less mobile apoplastic compartments leading to a reduction in hydraulic capacitance. This collection of foliar traits allows giant sequoia to routinely, but safely, operate close to its TLP, and suggests that gravity plays a major role in the water relations of Earth's largest tree species. PMID- 28985378 TI - Professional competence in a health promotion program in the Netherlands. AB - Health promotion for senior citizens ('seniors') is an increasingly important factor in health and welfare policy, having important implications for occupational therapy. The health promotion program 'Healthy and Active Aging' originated in the US, has been modified and adapted to the Dutch context and has been implemented in community contexts. This study aimed to generate an in-depth understanding of the Healthy and Active Aging program and to use this knowledge to inform professional practice. A naturalistic case study methodology was followed, using document analysis, observations, interviews and a group interview as data gathering methods. Data were analyzed and interpreted using narrative analyses. In this specific case, a small group of women joined the program. During 10 sessions, the participants explored the meaning of everyday activities for their self-perceived health and well-being. The key experience reported by the participants and professionals related to the positive ambience within the group, the emotional recognition among the participants and the responsive guidance of the professionals. This case showed how the framework of the program can be modified and tailored to the wishes and needs of the participating seniors. The group facilitators chose a subtle, responsive manner to support and motivate the participants. PMID- 28985379 TI - Xylogenesis in stems and roots after thinning in the boreal forest of Quebec, Canada. AB - The reduction of competition through thinning increases radial growth in the stem and roots of many conifer species. However, not much is known about the effect of thinning on the dynamics of wood formation and intra-annual development of the growth ring, especially in the roots, which are an essential part of the tree for stability and resource acquisition. The aim of this study was to evaluate the effect of an experimental thinning on the dynamics and phenology of xylogenesis in the stem and roots of black spruce and balsam fir. Experimental and control trees were selected in two mature even-aged stands, one black spruce (Picea mariana (Mill.) BSP) and one balsam fir (Abies balsamea (L.) Mill.). Wood microcores were collected weekly in the stem and roots from May to October for a period of 4 years. The onset and ending of each cell differentiation phase were computed, as well as growth rate and total cell production. Results show that thinning increased the cell production rate of stem and roots of black spruce and balsam fir. This higher daily growth rate caused an increase in the total number of cells produced by the cambium. The intensity of the treatment was sufficient to significantly increase light availability for residual trees, but insufficient to modify soil temperature and water content to a point at which a significant change in the timing or duration of xylogenesis would be induced. Thus, thinning increased cell production rate and total number of cells produced in both stem and roots, but did not result in a change in the phenology of wood formation that could lead to increased risks of frost damage in the spring or autumn. PMID- 28985380 TI - MEASUREMENTS IN AFGHANISTAN USING AN ACTIVE RADON EXPOSURE METER AND ASSESSMENT OF RELATED ANNUAL EFFECTIVE DOSE. AB - Radon gas concentrations in eight basements, four living rooms and four caves from different locations in Kabul and Panjsher, Afghanistan, were measured by using eight active radon exposure meters recently developed by the Helmholtz Center in Munich, Germany. The two-phase measurements lasted from a week to a year. In the first phase of measurements which lasted one week, the mean activity concentrations ranged from 6 to 120 Bq/m3 and 25 to 139 Bq/m3 for the basements and caves, respectively. In the second phase of measurements which lasted one year, the mean activity concentrations ranged from 33 to 2064 Bq/m3 and the corresponding effective annual doses calculated for the inhabitants were in the range between 0.6 and 33.4 mSv. As some of the values are rather high and exceed the recommended recommendations by IAEA and ICRP, based on the local conditions a number of simple recommendations has been proposed for the possible reduction of effective annual dose caused by radon in the measurement locations. PMID- 28985381 TI - COMPARISON OF PERSONAL DOSE EQUIVALENT Hp(10) IN 137CS RADIATION BETWEEN THE PRIMARY STANDARDS LABORATORIES OF JAPAN AND AUSTRALIA USING BeO OSL PERSONAL DOSEMETERS. AB - A comparison of personal dose equivalent Hp(10) for 137Cs radiation was conducted between the primary standards laboratories of Japan and Australia. A set of 120 commercially available passive BeO OSL dosemeters were used (Dosimetrics GmbH, Munich). The aim was to investigate the precision which could be obtained with this technique, and to confirm the personal dose equivalent delivery methods in each standards laboratory. A dose of 5 mSv was delivered to 40 dosemeters in each country, and 40 dosemeters were used as controls. The result of the comparison was a ratio of Hp(10) in Japan to Australia of 1.006 with a combined standard uncertainty of 3.2%. The statistical uncertainty was 0.32% indicating that passive dosemeters can be used for comparisons of high precision. PMID- 28985382 TI - Metabolome and transcriptome profiling reveal new insights into somatic embryo germination in Norway spruce (Picea abies). AB - Transcriptome, metabolome and histological profiling were performed on normal and aberrant somatic embryo germinants of Norway spruce (Picea abies L. Karst) providing a simplistic systems biology description of conifer germination. Aberrant germinants (AGs) formed periderm-like tissue at the apical pole and lacked shoot growth above the cotyledons. Transcriptome profiling (RNA Sequencing) revealed a total of 370 differentially expressed genes at >=1 or <=-1 log2-fold change, where 92% were down-regulated in AGs compared with normal germinants (NGs). Genes associated with shoot apical meristem formation were down regulated in AGs, or not differentially expressed between AGs and NGs. Genes involved in hormone signaling and transport were also down-regulated. Metabolite profiling by gas chromatography-mass spectrometry (MS) and liquid chromatography MS revealed biochemical difference between AGs and NGs, notably increased levels of sugars including glucose in AGs. Genes involved in glucose signaling were down regulated and genes involved in starch biosynthesis were up-regulated, suggesting involvement of sugar signaling during late embryo development and germination. The overall results provide new data enabling further studies to confirm potential markers for a normal germination process in conifers. PMID- 28985383 TI - ASSESSMENT OF RADIATION DOSE AND EXCESSIVE LIFE-TIME CANCER RISK FROM THE BUNAIR GRANITE, NORTHERN PAKISTAN. AB - Natural radioactivity was measured in Bunair Granite using high purity germanium gamma-ray spectrometer and compared to world's granites and building materials to access its suitability for the construction purpose. Average gamma-activities of 226Ra, 232Th and 40K were found to be 52.41, 58.41 and 1130.12 Bq kg-1, respectively. The Indoor and outdoor radiation indices including excessive life time cancer risk (ELCR) were calculated. The average indoor ELCR was estimated as 3.49 * 10-3. The average outdoor ELCR was assessed as 0.46 * 10-3. As a basic building material Bunair Granite should be on low propriety. For flooring, facing the buildings and as Table tops, in kitchens and other utilities it is safe. PMID- 28985385 TI - Evaluating an Indigenous health curriculum for diabetes prevention: engaging the community through talking circles and knowledge translation of results. AB - Background: Kahnawa:ke is a Kanien'keha:ka (Mohawk) community in Quebec, Canada. In 1997, the community-controlled Kateri Memorial Hospital Centre in partnership with the Kahnawake Education Center, and the Kahnawake Schools Diabetes Prevention Project (KSDPP) developed an elementary school diabetes prevention health education program, aimed to increase knowledge of Type 2 diabetes, healthy eating and active lifestyles. Long-term goals for KSDPP community and school interventions are to decrease obesity and diabetes. Objectives: To evaluate the Kateri Memorial Hospital Centre Health Education Program for Diabetes Prevention (HEP) and use key principles of knowledge translation to promote understanding of results to upgrade HEP content and improve delivery. Methods: A KSDPP community based participatory research team used mixed methods for evaluation, combining a cross-sectional survey for 23 teachers with interviews of two elementary school principals and three culturally appropriate Indigenous talking circles with HEP authors, teachers and parents. Questionnaire results were presented as descriptive statistics. The thematic textual analysis identified emerging themes from talking circles and interviews. Results: Facilitators of HEP delivery were an acknowledgement of its importance; appreciation of prepared lesson plans for teachers; and KSDPP's strong community presence. Barriers included reduced administrative support and instructional time due to competing academic demands; the need for increased Kanien'keha:ka cultural content; and outdated resource materials. Recommendations included increasing teacher training, Kanien'keha:ka cultural content and administrative support. Conclusion: Community researchers undertook detailed knowledge translation activities of facilitators, barriers and recommendations with hospital and education centre administrators and Kahnawa:ke community to maximize uptake of findings before external dissemination of results. PMID- 28985384 TI - Putting it in Context: Linking Auditory Processing with Social Behavior Circuits in the Vertebrate Brain. AB - Context is critical to the adaptive value of communication. Sensory systems such as the auditory system represent an important juncture at which information on physiological state or social valence can be added to communicative information. However, the neural pathways that convey context to the auditory system are not well understood. The serotonergic system offers an excellent model to address these types of questions. Serotonin fluctuates in the mouse inferior colliculus (IC), an auditory midbrain region important for species-specific vocalizations, during specific social and non-social contexts. Furthermore, serotonin is an indicator of the valence of event-based changes within individual social interactions. We propose a model in which the brain's social behavior network serves as an afferent effector of the serotonergic dorsal raphe nucleus in order to gate contextual release of serotonin in the IC. Specifically, discrete vasopressinergic nuclei within the hypothalamus and extended amygdala that project to the dorsal raphe are functionally engaged during contexts in which serotonin fluctuates in the IC. Since serotonin strongly influences the responses of IC neurons to social vocalizations, this pathway could serve as a feedback loop whereby integrative social centers modulate their own sources of input. The end result of this feedback would be to produce a process that is geared, from sensory input to motor output, toward responding appropriately to a dynamic external world. PMID- 28985386 TI - Economic shocks and health resilience: lessons from the Russian Federation. PMID- 28985387 TI - Neuropsychiatric symptoms and psychotropic drug use in patients with dementia in general practices. AB - Background: Neuropsychiatric symptoms (NPS) frequently occur in community dwelling patients with dementia and they are also frequently prescribed psychotropic drugs. The prescription of psychotropic drugs has been found to be associated with the level of NPS. Data on NPS in patients with dementia in general practices are scarce. Objectives: The aim of this study was to assess the prevalence rates of NPS and psychotropic drug use (PDU) in patients with dementia in general practices. Methods: We analyzed data from the baseline measurement of a prospective cohort study in a sample of (Dutch) patients in general practices. Prevalence rates of NPS and subsyndromes assessed with the Neuropsychiatric Inventory (NPI) and of PDU were calculated. Prevalence rates of individual NPS are presented both as clinically relevant symptoms (NPI symptom score >= 4) and as prevalence rates of symptoms with symptom score > 0. Results: Of the 117 patients, more than 90% had at least one symptom and more than 65% had at least one clinically relevant symptom. The most common NPS were agitation/aggression, dysphoria/depression and irritability/lability. The most common clinically relevant NPS were aberrant motor behaviour, agitation/aggression and apathy/indifference. Only 28.7% of the patients used at least one, 7.0% used at least two different and 1.7% used at least three different types of psychotropic drugs (excluding anti-dementia medication). Conclusions: NPS are highly prevalent in patients with dementia in general practices, but PDU is rather low. The most common clinically relevant NPS were aberrant motor behaviour, agitation/aggression and apathy/indifference. PMID- 28985388 TI - Leaf surface traits and water storage retention affect photosynthetic responses to leaf surface wetness among wet tropical forest and semiarid savanna plants. AB - While it is reasonable to predict that photosynthetic rates are inhibited while leaves are wet, leaf gas exchange measurements during wet conditions are challenging to obtain due to equipment limitations and the complexity of canopy atmosphere interactions in forested environments. Thus, the objective of this study was to evaluate responses of seven tropical and three semiarid savanna plant species to simulated leaf wetness and test the hypotheses that (i) leaf wetness reduces photosynthetic rates (Anet), (ii) leaf traits explain different responses among species and (iii) leaves from wet environments are better adapted for wet leaf conditions than those from drier environments. The two sites were a tropical rainforest in northern Costa Rica with ~4200 mm annual rainfall and a savanna in central Texas with ~1100 mm. Gas exchange measurements were collected under dry and wet conditions on five sun-exposed leaf replicates from each species. Additional measurements included leaf wetness duration and stomatal density. We found that Anet responses varied greatly among species, but all plants maintained a baseline of activity under wet leaf conditions, suggesting that abaxial leaf Anet was a significant percentage of total leaf Anet for amphistomatous species. Among tropical species, Anet responses immediately after wetting ranged from -31% (Senna alata (L.) Roxb.) to +21% (Zamia skinneri Warsz. Ex. A. Dietr.), while all savanna species declined (up to -48%). After 10 min of drying, most species recovered Anet towards the observed status prior to wetting or surpassed it, with the exception of Quercus stellata Wangenh., a savanna species, which remained 13% below Anet dry. The combination of leaf wetness duration and leaf traits, such as stomatal density, trichomes or wax, most likely influenced Anet responses positively or negatively. There was also overlap between leaf traits and Anet responses of savanna and tropical plants. It is possible that these species converge on a relatively conservative response to wetness, each for divergent purposes (cooling, avoiding stomatal occlusion, or by several unique means of rapid drying). A better understanding of leaf wetness inhibiting photosynthesis is vital for accurate modeling of growth in forested environments; however, species adapted for wet environments may possess compensatory traits that mitigate these effects. PMID- 28985390 TI - Roles and Mechanistic Bases of Glucocorticoid Regulation of Avian Reproduction. AB - To maximize fitness, organisms must invest energetic and nutritional resources into developing, activating, and maintaining reproductive physiology and behavior. Corticosterone (CORT), the primary avian glucocorticoid, regulates energetic reserves to meet metabolic demands. At low (baseline) plasma levels, CORT activates avian mineralocorticoid receptors and may stimulate lipid mobilization, foraging activity, and feeding behavior. During stress in birds, elevated plasma CORT also stimulates glucocorticoid receptors and may promote glycemia, lipolysis, and proteolysis. Furthermore, CORT orchestrates physiological and behavioral adjustments to perceived threats. While many avian studies demonstrate effects of CORT on reproduction, few studies have elucidated the mechanisms, including receptor activation and site(s) of action, which underlie these effects. Even fewer studies have investigated how low and elevated plasma CORT regulates energetic reserves to meet the metabolic demands of reproduction. Here, we propose several hypotheses to clarify the direct and indirect effects of CORT on avian reproductive physiology and behavior. In addition, we emphasize the need for new manipulative studies involving alterations of endogenous plasma CORT levels and/or food availability to elucidate how CORT regulates the energetic demands of reproduction. PMID- 28985389 TI - Water retained in tall Cryptomeria japonica leaves as studied by infrared micro spectroscopy. AB - Recent studies in the tallest tree species suggest that physiological and anatomical traits of tree-top leaves are adapted to water-limited conditions. In order to examine water retention mechanism of leaves in a tall tree, infrared (IR) micro-spectroscopy was conducted on mature leaf cross-sections of tall Cryptomeria japonica D. Don from four different heights (51, 43, 31 and 19 m). We measured IR transmission spectra and mainly analyzed OH (3700-3000 cm-1) and C-O (1190-845 cm-1) absorption bands, indicating water molecules and sugar groups, respectively. The changes in IR spectra of leaf sections from different heights were compared with bulk-leaf hydraulics. Both average OH band area of the leaf sections and leaf water content were larger in the upper-crown, while osmotic potential at saturation did not vary with height, suggesting higher dissolved sugar contents of upper-crown leaves. As cell-wall is the main cellular structure of leaves, we inferred that larger average C-O band area of upper-crown leaves reflected higher content of structural polysaccharides such as cellulose, hemicellulose and pectin. Infrared micro-spectroscopic imaging showed that the OH and C-O band areas are large in the vascular bundle, transfusion tissue and epidermis. Infrared spectra of individual tissue showed that much more water is retained in vascular bundle and transfusion tissue than mesophyll. These results demonstrate that IR micro-spectroscopy is a powerful tool for visualizing detailed, quantitative information on the spatial distribution of chemical substances within plant tissues, which cannot be done using conventional methods like histochemical staining. The OH band could be well reproduced by four Gaussian OH components around 3530 (free water: long H bond), 3410 (pectin-like OH species), 3310 (cellulose-like OH species) and 3210 (bound water: short H bond) cm-1, and all of these OH components were higher in the upper crown while their relative proportions did not vary with height. Based on the spectral analyses, we inferred that polysaccharides play a key role in biomolecular retention of water in leaves of tall C. japonica. PMID- 28985391 TI - EXTRAPOLATION METHOD FOR MAXIMAL AND 24-H AVERAGE LTE TDD EXPOSURE ESTIMATION. AB - The Long-Term Evolution (LTE) system represents the evolution of the Universal Mobile Telecommunication System technology. This technology introduces two duplex modes: Frequency Division Duplex and Time Division Duplex (TDD). Despite having experienced a limited expansion in the European countries since the debut of the LTE technology, a renewed commercial interest for LTE TDD technology has recently been shown. Therefore, the development of extrapolation procedures optimised for TDD systems becomes crucial, especially for the regulatory authorities. This article presents an extrapolation method aimed to assess the exposure to LTE TDD sources, based on the detection of the Cell-Specific Reference Signal power level. The method introduces a betaTDD parameter intended to quantify the fraction of the LTE TDD frame duration reserved for downlink transmission. The method has been validated by experimental measurements performed on signals generated by both a vector signal generator and a test Base Transceiver Station installed at Linkem S.p.A facility in Rome. PMID- 28985392 TI - Moving in Dim Light: Behavioral and Visual Adaptations in Nocturnal Ants. AB - Visual navigation is a benchmark information processing task that can be used to identify the consequence of being active in dim-light environments. Visual navigational information that animals use during the day includes celestial cues such as the sun or the pattern of polarized skylight and terrestrial cues such as the entire panorama, canopy pattern, or significant salient features in the landscape. At night, some of these navigational cues are either unavailable or are significantly dimmer or less conspicuous than during the day. Even under these circumstances, animals navigate between locations of importance. Ants are a tractable system for studying navigation during day and night because the fine scale movement of individual animals can be recorded in high spatial and temporal detail. Ant species range from being strictly diurnal, crepuscular, and nocturnal. In addition, a number of species have the ability to change from a day to a night-active lifestyle owing to environmental demands. Ants also offer an opportunity to identify the evolution of sensory structures for discrete temporal niches not only between species but also within a single species. Their unique caste system with an exclusive pedestrian mode of locomotion in workers and an exclusive life on the wing in males allows us to disentangle sensory adaptations that cater for different lifestyles. In this article, we review the visual navigational abilities of nocturnal ants and identify the optical and physiological adaptations they have evolved for being efficient visual navigators in dim-light. PMID- 28985393 TI - Reason and Paradox in Medical and Family Law: Shaping Children's Bodies. PMID- 28985394 TI - A Validated Method for the Detection of 32 Bath Salts in Oral Fluid. AB - Workplace drug testing in Australia is usually adherent to one of two standards, AS/NZS 4308:2008 for urine or AS 4760:2006 for oral fluid. These standards prescribe the drugs tested, devices used and testing methodology followed by the testing agency. However, they are not comprehensive and for many years workers have been able to consume novel psychoactive substances to avoid detection and without consequences. Here, we present a validated method for the detection of 32 Synthetic Stimulant and Hallucogenic drugs, commonly sold as bath salts, in oral fluid. These drugs are cathinone, ephedrone, methylone, flephedrone, MDA, PMA, methedrone, TMA, MDMA, butylone, mephedrone, MDEA, MEC, pentedrone, MBDB, MTA, Alpha-PVP, MPBP, 2C-B, MDPV, DOB, 2C-T-2, TFMPP, DOET, 2C-T-7, naphyrone, MDAI, FMA, DMA, 25C-NBOMe, 25B-NBOMe and 25T4-NBOMe. Sample preparation was undertaken using a simple protein precipitation in acetonitrile. Chromatographic separation was achieved in 7.5 min on a Kinetex F5 column (50 mm * 3 mm * 2.6 MUm) using 0.1% formic acid in water and acetonitrile as the mobile phases. The method was validated with limit of detection (1 ng/mL), limit of quantitation (2.5 ng/mL), selectivity, linearity (2.5-500 ng/mL), accuracy (85.3-108.4% of the target concentration) and precision (1.9-14%). This method was applied to 12 samples previously submitted for routine testing and two were found to contain 2-CB and DOB (5 and 4 ng/mL) and, MPBP and TFMPP (both at 4 ng/mL). This method provides for the rapid detection of a large number of compounds in oral fluid which is readily applicable to routine testing laboratories. PMID- 28985396 TI - EYE LENS DOSIMETRY WITHIN THE CARDIAC CATHETERISATION LABORATORY-ARE ANCILLARY STAFF BEING FORGOTTEN? AB - Eye lens doses have been widely explored for interventional clinicians, however, data for ancillary staff is limited. Eye doses have been measured using a headband technique for clinicians, specialist registrars, nurses and radiographers working in a cardiac catheterisation laboratory in a UK hospital. Workload was found to be significantly higher for ancillary staff, and consequently, despite the absolute monthly collar doses and other indicators such as eye dose/KAP and eye dose/procedure being highest for clinicians, our study found there was no significant difference in the monthly eye dose readings between the clinicians and nurses (p = 0.82), and clinicians and radiographers (p = 0.72). The average eye dose/collar dose ratios were 0.71 and 0.61 for cardiologists and SPRs, but ratios above one were found for nurses and radiographers. This work expands on the eye dose data available for ancillary staff and demonstrates that eye dosimetry for these workers should not be overlooked. PMID- 28985397 TI - A Rare Cause of Torticollis: Grisel Syndrome. AB - Painful torticollis in children requires specific attention. Grisel syndrome is diagnosed on suspicion in patients with recent or history of ongoing upper respiratory tract infections and in patients with restriction of movement or deformity following oto-rhino-laryngologic surgery. Pediatricians should be aware of this condition because early diagnosis and intervention are critical for prognosis in Grisel syndrome. PMID- 28985399 TI - Have community health workers increased the delivery of maternal and child healthcare in India? AB - Background: Accredited Social Health Activists (ASHAs) are community health workers in rural India. This study estimates the proportion of villages with an ASHA and examines the impact of increased ASHA placement on changes in healthcare. Methods: Information about ASHA placement and maternal and child healthcare was obtained from the District-Level Household Surveys from 2007 to 2008 and 2012 to 2013. In this ecological analysis, the difference in district level proportions of maternal and child healthcare outcomes between 2012-13 and 2007-08 was regressed onto the difference in ASHA placement between those years. Results: Within 218 districts from 21 states, the average proportion of villages with an ASHA increased from 39.1 to 76.2%, unmet need for family planning increased from 14.7 to 22.4%, institutional delivery increased from 61.6 to 82.5%, and full immunization coverage decreased from 71.2 to 65.1%. A 1% increase in ASHA placement resulted in 0.05% less unmet need for family planning and 0.22% more full immunization, but no changes in institutional delivery. Conclusions: ASHAs provide essential services to their community by acting as a conduit to healthcare services, but they may require more training about certain services like promoting institutional delivery to be effective in increasing access to these health services. PMID- 28985398 TI - Prognostic importance of pathological response to neoadjuvant chemotherapy followed by definitive surgery in advanced oral squamous cell carcinoma. AB - Objective: The clinical importance of neoadjuvant chemotherapy (NAC) followed by definitive surgery was retrospectively investigated in clinical Stage III/IV oral squamous cell carcinoma (OSCC). Methods: Surgery was performed for OSCC in 164 patients, including 72 patients who had received NAC (two cycles of cisplatin and fluorouracil) prior to surgery from January 2004 to December 2014. The clinical characteristics and survival parameters of the groups that received and did not receive NAC were evaluated. The pathological response was classified as Grade 0 (no effect), 1a (very slight effect), 1b (slight effect), 2 (moderate effect) or 3 (marked effect), and its correlation with prognosis was investigated. Results: There were no statistical differences in survival indicators between patients who received NAC and those who did not (overall survival, P = 0.75). The proportion of patients who received NAC in the effective NAC group (Grades 1b, 2, and 3) was 52.8%. After a median follow-up of 35 months, overall survival (P = 0.01), disease-free survival (P = 0.002), locoregional disease-free survival (P = 0.003), and distant disease-free survival (P = 0.01) were significantly better in the effective NAC group than in the less effective NAC group (Grades 0 and 1a). Conclusion: Although NAC had a limited effect on disease prognosis in OSCC, the pathological response to NAC could be an important prognostic indicator for advanced OSCC. PMID- 28985395 TI - Nonhuman Primates and Translational Research-Cardiovascular Disease. AB - Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States. Human epidemiological studies provide challenges for understanding mechanisms that regulate initiation and progression of CVD due to variation in lifestyle, diet, and other environmental factors. Studies describing metabolic and physiologic aspects of CVD, and those investigating genetic and epigenetic mechanisms influencing CVD initiation and progression, have been conducted in multiple Old World nonhuman primate (NHP) species. Major advantages of NHPs as models for understanding CVD are their genetic, metabolic, and physiologic similarities with humans, and the ability to control diet, environment, and breeding. These NHP species are also genetically and phenotypically heterogeneous, providing opportunities to study gene by environment interactions that are not feasible in inbred animal models. Each Old World NHP species included in this review brings unique strengths as models to better understand human CVD. All develop CVD without genetic manipulation providing multiple models to discover genetic variants that influence CVD risk. In addition, as each of these NHP species age, their age-related comorbidities such as dyslipidemia and diabetes are accelerated proportionally 3 to 4 times faster than in humans.In this review, we discuss current CVD-related research in NHPs focusing on selected aspects of CVD for which nonprimate model organism studies have left gaps in our understanding of human disease. We include studies on current knowledge of genetics, epigenetics, calorie restriction, maternal calorie restriction and offspring health, maternal obesity and offspring health, nonalcoholic steatohepatitis and steatosis, Chagas disease, microbiome, stem cells, and prevention of CVD. PMID- 28985400 TI - Dramatic Differences in Gut Bacterial Densities Correlate with Diet and Habitat in Rainforest Ants. AB - Abundance is a key parameter in microbial ecology, and important to estimates of potential metabolite flux, impacts of dispersal, and sensitivity of samples to technical biases such as laboratory contamination. However, modern amplicon-based sequencing techniques by themselves typically provide no information about the absolute abundance of microbes. Here, we use fluorescence microscopy and quantitative polymerase chain reaction as independent estimates of microbial abundance to test the hypothesis that microbial symbionts have enabled ants to dominate tropical rainforest canopies by facilitating herbivorous diets, and compare these methods to microbial diversity profiles from 16S rRNA amplicon sequencing. Through a systematic survey of ants from a lowland tropical forest, we show that the density of gut microbiota varies across several orders of magnitude among ant lineages, with median individuals from many genera only marginally above detection limits. Supporting the hypothesis that microbial symbiosis is important to dominance in the canopy, we find that the abundance of gut bacteria is positively correlated with stable isotope proxies of herbivory among canopy-dwelling ants, but not among ground-dwelling ants. Notably, these broad findings are much more evident in the quantitative data than in the 16S rRNA sequencing data. Our results provide quantitative context to the potential role of bacteria in facilitating the ants' dominance of the tropical rainforest canopy, and have broad implications for the interpretation of sequence-based surveys of microbial diversity. PMID- 28985401 TI - Clinical Characteristics of Nosocomial Bloodstream Infections in Neonates in Two Hospitals, China. AB - Background: The improvement of medical condition requires prolonged hospital stays, which increase the risk of nosocomial bloodstream infections (BSIs). Methods: All nosocomial BSI newborns in two hospitals were included, and the demographic and clinical characteristics of bacteremia patients were obtained from the information systems. Isolates were identified by biochemical assays. Antimicrobial susceptibility was determined using disk diffusion method. Results: Except for three same risk factors, intubation with mechanical ventilation was a risk factor in Chongqing, while low birth weight was a risk factor in Henan. Klebsiella pneumoniae was the predominant strain in Chongqing, and Escherichia coli was the most prevalent strain in Henan. The resistance rate of gram-negative bacteria in Henan was higher than that of strains in Chongqing. Conclusions: The risk factors and resistance rate of pathogens were different in different areas. Therefore, treatment protocols should be established based on the trends of drug resistance and bacterial spectrum. PMID- 28985402 TI - Case Comment-Webster V Burton Hospital NHS Foundation Trust. PMID- 28985403 TI - Anthropometric Parameters of HIV-Infected and HIV-Uninfected Mothers and their Premature Infants. AB - This study aimed to assess the maternal anthropometric parameters of human immunodeficiency virus (HIV)-infected and HIV-uninfected mothers as well as to assess the neonatal anthropometric parameters of premature infants in relation to maternal anthropometric parameters (weight, height and mid-upper-arm circumference), HIV status and anti-retroviral therapy (ART) regimen. Study participants included HIV-infected and HIV-uninfected mothers who gave birth to premature infants. All HIV-infected mothers received ART. The incidence of intra uterine growth restriction (IUGR) among premature infants was high. Maternal anthropometric parameters, HIV status and ART exposure showed no association with IUGR in this study. Sufficient maternal ART exposure may positively influence head circumference at birth, which might determine the neurodevelopmental outcome of these infants. PMID- 28985405 TI - Katrien Devolder, The Ethics of Embryonic Stem Cell Research. PMID- 28985406 TI - The Animal Welfare Act and the Conduct and Publishing of Wildlife Research in the United States. AB - In the US, the Animal Welfare Act (AWA) and its enabling regulations (AWAR) cover all warm-blooded animals used for research, testing, experimentation, or exhibition. The only exceptions, made in the enabling regulations, are for two genera of rodents and for birds, bred specifically for research (meaning even those exceptions do not apply to wild birds and wild rodents of those genera) and for farm and agricultural animals. Research using animals covered by the AWA and AWAR must be reviewed and approved by an Animal Care and Use Committee (ACUC) properly constituted according to AWA and AWAR. A review of Instructions to Authors and policy statements offered by 106 journals classified by their content as containing articles that were oriented largely toward disease, ecology, or general, showed that disease-oriented journals originating in the United States and those produced by professional societies and government agencies have a higher explicit requirement for ACUC review than do disease-oriented journals produced outside the United States or those produced commercially. Journals with a general orientation that are produced outside the United States or commercially had much higher rates of requiring explicit statements for ACUC review than generally-oriented journals produced in the United States or those produced by professional societies and government agencies. Ecology journals had low rates of explicit statements for ACUC review regardless of geographic origins or sources. PMID- 28985407 TI - USTUR WHOLE-BODY CASE 0212: 17-YEAR FOLLOW-UP OF PLUTONIUM CONTAMINATED WOUND. AB - The National Council of Radiation Protection and Measurements' (NCRP) wound model was applied to the bioassay data from a United States Transuranium and Uranium Registries' whole-body tissue donor, Case 0212. This individual was exposed to plutonium nitrate as a result of an occupational wound injury and he underwent extensive chelation treatment with Ca-DTPA. All major soft tissues and bones were collected post-mortem and radiochemically analyzed for 238Pu, 239,240Pu and 241Am. The 239,240Pu activity in the total body was estimated to be 232.0 Bq, with 80.3 Bq retained in the liver, 115.1 Bq in the skeleton and 14.3 Bq in the wound. The maximum likelihood method was used to simultaneously fit the 'post treatment' urinary excretion and post-mortem liver and skeleton retention data. It was demonstrated that the deposited material was predominantly a strongly retained soluble compound (nitrate) with a 22% fraction of plutonium particles. The residual intake, the amount of plutonium deposited in the wound that was not removed from the system by Ca-DTPA, was estimated to be 288 Bq. The resulting committed effective dose was 134 mSv. Accounting for plutonium eliminated in the urine during chelation therapy, the actual 'untreated' intake was 1204 Bq, and the projected committed effective dose was 567 mSv. Hence, DTPA treatment reduced the dose by a factor of 4. PMID- 28985404 TI - Small RNA profiling in Chlamydomonas: insights into chloroplast RNA metabolism. AB - In Chlamydomonas reinhardtii, regulation of chloroplast gene expression is mainly post-transcriptional. It requires nucleus-encoded trans-acting protein factors for maturation/stabilization (M factors) or translation (T factors) of specific target mRNAs. We used long- and small-RNA sequencing to generate a detailed map of the transcriptome. Clusters of sRNAs marked the 5' end of all mature mRNAs. Their absence in M-factor mutants reflects the protection of transcript 5' end by the cognate factor. Enzymatic removal of 5'-triphosphates allowed identifying those cosRNA that mark a transcription start site. We detected another class of sRNAs derived from low abundance transcripts, antisense to mRNAs. The formation of antisense sRNAs required the presence of the complementary mRNA and was stimulated when translation was inhibited by chloramphenicol or lincomycin. We propose that they derive from degradation of double-stranded RNAs generated by pairing of antisense and sense transcripts, a process normally hindered by the traveling of the ribosomes. In addition, chloramphenicol treatment, by freezing ribosomes on the mRNA, caused the accumulation of 32-34 nt ribosome-protected fragments. Using this 'in vivo ribosome footprinting', we identified the function and molecular target of two candidate trans-acting factors. PMID- 28985408 TI - A common neural code for social and monetary rewards in the human striatum. AB - Although managing social information and decision making on the basis of reward is critical for survival, it remains uncertain whether differing reward type is processed in a uniform manner. Previously, we demonstrated that monetary reward and the social reward of good reputation activated the same striatal regions including the caudate nucleus and putamen. However, it remains unclear whether overlapping activations reflect activities of identical neuronal populations or two overlapping but functionally independent neuronal populations. Here, we re analyzed the original data and addressed this question using multivariate-pattern analysis and found evidence that in the left caudate nucleus and bilateral nucleus accumbens, social vs monetary reward were represented similarly. The findings suggest that social and monetary rewards are processed by the same population of neurons within these regions of the striatum. Additional findings demonstrated similar neural patterns when participants experience high social reward compared to viewing others receiving low social reward (potentially inducing schadenfreude). This is possibly an early indication that the same population of neurons may be responsible for processing two different types of social reward (good reputation and schadenfreude). These findings provide a supplementary perspective to previous research, helping to further elucidate the mechanisms behind social vs non-social reward processing. PMID- 28985409 TI - Dynamic stepwise opening of integron attC DNA hairpins by SSB prevents toxicity and ensures functionality. AB - Biologically functional DNA hairpins are found in archaea, prokaryotes and eukaryotes, playing essential roles in various DNA transactions. However, during DNA replication, hairpin formation can stall the polymerase and is therefore prevented by the single-stranded DNA binding protein (SSB). Here, we address the question how hairpins maintain their functional secondary structure despite SSB's presence. As a model hairpin, we used the recombinogenic form of the attC site, essential for capturing antibiotic-resistance genes in the integrons of bacteria. We found that attC hairpins have a conserved high GC-content near their apical loop that creates a dynamic equilibrium between attC fully opened by SSB and a partially structured attC-6-SSB complex. This complex is recognized by the recombinase IntI, which extrudes the hairpin upon binding while displacing SSB. We anticipate that this intriguing regulation mechanism using a base pair distribution to balance hairpin structure formation and genetic stability is key to the dissemination of antibiotic resistance genes among bacteria and might be conserved among other functional hairpins. PMID- 28985410 TI - Distribution of optometric practices relative to deprivation index in Scotland. AB - Background: The UK National Health Service aims to provide universal availability of healthcare, and eye-care availability was a primary driver in the development of the Scottish General Ophthalmic Services (GOS) model. Accordingly, a relatively equal distribution of optometry practices across socio-economic areas is required. We examined practice distribution relative to deprivation. Methods: 672 practices were sampled from nine Health Boards within Scotland. Practices were assigned a deprivation ranking by referencing their postcode with the Scottish Index of Multiple Deprivation (SIMD) tool (Scottish Executive National Statistics: General Report. 2016). Results: Averaged across Health Boards, the share of practices for the five deprivation quintiles was 25, 33, 18, 14 and 11% from most to least deprived area, respectively. Although there was some variation of relative practice distribution in individual Health Boards, 17 of the 45 regions (nine Health Boards, five quintiles) had a close balance between population and share of practices. There was no clear pattern of practice distribution as a function of deprivation rank. Analysis revealed good correlation between practice and population share for each Health Board, and for the combined data (R2 = 0.898, P < 0.01). Conclusion: Distribution of optometry practices is relatively balanced across socio-economic areas, suggesting that differences in eye-examination uptake across social strata are unrelated to service availability. PMID- 28985412 TI - Validated Chromatographic Methods for the Simultaneous Determination of Sulfacetamide Sodium and Prednisolone Acetate in their Ophthalmic Suspension. AB - Two specific, sensitive, rapid and accurate chromatographic methods have been developed, optimized and validated for the simultaneous determination of sulfacetamide sodium and prednisolone acetate in pure forms and in their binary mixture. The first method is an isocratic Reversed phase-high performance liquid chromatography method where a rapid separation was achieved on a Zorbax ODS column using a green mobile phase of methanol: water (80:20, v/v) and pH adjusted to 5.0 +/- 0.2 with orthophosphoric acid. The retention times (tR) were 2.21 and 3.64 min for sulfacetamide sodium and prednisolone acetate, respectively. The separated peaks were detected at 254 nm. The second method is a thin layer chromatography-densitometric method where the two drugs were separated on silica gel plates using a simple mobile phase of chloroform: methanol (90:10, v/v) and scanning of the separated bands was at 254 nm. The retardation factors (Rf) values were 0.37 and 0.64 for sulfacetamide sodium and prednisolone acetate, respectively. The suggested methods were validated in compliance with the ICH guidelines and were successfully applied to determine both drugs in their pure forms, laboratory prepared mixtures and dosage form. The obtained results were statistically compared to the official method where no significant difference was obtained with respect to both accuracy and precision. PMID- 28985413 TI - THE CHALLENGES IN THE ESTIMATION OF THE EFFECTIVE DOSE WHEN WEARING RADIOPROTECTIVE GARMENTS. AB - The performance of a single or double dosimetry (SD or DD) algorithm on estimating effective dose wearing radioprotective garments (ERPG) depends on the specific irradiation conditions. This study investigates the photon energies and angles of incidence for which the estimation of ERPG with the personal dose equivalents measured over and under the RPG (Ho and Hu) becomes more challenging. The energy and angular dependences of ERPG, Ho and Hu were Monte Carlo calculated for photon exposures. The personal dosimeter of SCK . CEN was modeled and used to determine Ho and Hu. Different SD and DD algorithms were tested and critical exposure conditions were identified. Moreover, the influence of calibration methods was investigated for the SCK . CEN dosimeter when worn over RPG. We found that the accuracy with which ERPG is calculated using SD and DD is strongly dependent on the energy and angle of incidence of photons. Also, the energy of the photon beam used to calibrate the Ho dosimeter can bias the estimation of ERPG. PMID- 28985411 TI - Tethered-variable CL bispecific IgG: an antibody platform for rapid bispecific antibody screening. AB - Bispecific antibodies offer a clinically validated platform for drug discovery. In generating functionally active bispecific antibodies, it is necessary to identify a unique parental antibody pair to merge into a single molecule. However, technologies that allow high-throughput production of bispecific immunoglobulin Gs (BsIgGs) for screening purposes are limited. Here, we describe a novel bispecific antibody format termed tethered-variable CLBsIgG (tcBsIgG) that allows robust production of intact BsIgG in a single cell line, concurrently ensuring cognate light chain pairing and preserving key antibody structural and functional properties. This technology is broadly applicable in the generation of BsIgG from a variety of antibody isotypes, including human BsIgG1, BsIgG2 and BsIgG4. The practicality of the tcBsIgG platform is demonstrated by screening BsIgGs generated from FGF21-mimetic anti-Klotho-beta agonistic antibodies in a combinatorial manner. This screen identified multiple biepitopic combinations with enhanced agonistic activity relative to the parental monoclonal antibodies, thereby demonstrating that biepitopic antibodies can acquire enhanced functionality compared to monospecific parental antibodies. By design, the tcBsIgG format is amenable to high-throughput production of large panels of bispecific antibodies and thus can facilitate the identification of rare BsIgG combinations to enable the discovery of molecules with improved biological function. PMID- 28985414 TI - PtoMYB170 positively regulates lignin deposition during wood formation in poplar and confers drought tolerance in transgenic Arabidopsis. AB - Wood formation is a complex developmental process under multi-level transcriptional control executed by a large set of transcription factors. However, only limited members have been characterized to be key regulators of lignin biosynthesis in poplar. Here we report the conserved and unique functions of PtoMYB170, a transcription factor identified from Populus tomentosa (Chinese white poplar), in lignin deposition and drought tolerance in comparison with its duplicate paralog PtoMYB216. PtoMYB170 is preferentially expressed in young leaves and xylem tissues. Overexpression of PtoMYB170 in transgenic poplar plants resulted in stronger lignification and more thickened secondary wall in xylem compared with wild-type plants, whereas the CRISPR/Cas9-generated mutation of PtoMYB170 weakened lignin deposition, thereby leading to a more flexible and collapsed xylem phenotype. Transient expression experiments demonstrated that PtoMYB170 specifically activated the expression of lignin biosynthetic genes, consistent with the function of PtoMYB216. However, GUS staining assays revealed that PtoMYB170 was specifically expressed in guard cells of transgenic Arabidopsis while PtoMYB216 was not. Heterologous expression of PtoMYB170 in Arabidopsis enhanced stomatal closure in the dark and resulted in drought tolerance of the transgenic plants through reduced water loss, indicating a diversified role from PtoMYB216. These results revealed the PtoMYB170-dependent positive transcriptional regulation on lignin deposition in poplar and its coordinated function in enhancing drought tolerance by promoting dark-induced stomatal closure. PMID- 28985415 TI - Letter to the Editor. PMID- 28985416 TI - EVLncRNAs: a manually curated database for long non-coding RNAs validated by low throughput experiments. AB - Long non-coding RNAs (lncRNAs) play important functional roles in various biological processes. Early databases were utilized to deposit all lncRNA candidates produced by high-throughput experimental and/or computational techniques to facilitate classification, assessment and validation. As more lncRNAs are validated by low-throughput experiments, several databases were established for experimentally validated lncRNAs. However, these databases are small in scale (with a few hundreds of lncRNAs only) and specific in their focuses (plants, diseases or interactions). Thus, it is highly desirable to have a comprehensive dataset for experimentally validated lncRNAs as a central repository for all of their structures, functions and phenotypes. Here, we established EVLncRNAs by curating lncRNAs validated by low-throughput experiments (up to 1 May 2016) and integrating specific databases (lncRNAdb, LncRANDisease, Lnc2Cancer and PLNIncRBase) with additional functional and disease-specific information not covered previously. The current version of EVLncRNAs contains 1543 lncRNAs from 77 species that is 2.9 times larger than the current largest database for experimentally validated lncRNAs. Seventy-four percent lncRNA entries are partially or completely new, comparing to all existing experimentally validated databases. The established database allows users to browse, search and download as well as to submit experimentally validated lncRNAs. The database is available at http://biophy.dzu.edu.cn/EVLncRNAs. PMID- 28985417 TI - School-level factors associated with teacher connectedness: a multilevel analysis of the structural and relational school determinants of young people's health. AB - Background: Conducting research on the antecedents of teacher connectedness (TC) is key to inform intervention and policy that can leverage the public health potential of teachers for young people's well-being. As part of the EU-funded Teacher Connectedness Project, this study aims to examine the contribution of a variety of school-level factors (including type of school, school size, student teacher ratio, students per class and teacher gender). Methods: Sample consisted of 5335 adolescents aged 11, 13 and 15 years that had participated in the HBSC study in England. Multilevel multinomial regression was used to examine the contributions of sociodemographic and school-level factors to TC. Results: TC was lower in older adolescents and those from less affluent families, but similar in boys and girls. Regarding school-level factors, it was not the size of the school but the ratio of students per teacher which was significantly associated to TC, with higher student-teacher ratio being significantly associated with lower odds of medium-to-high TC. Some differences between mixed and all-girls schools were also found. Conclusions: Health promotion strategies targeting student-teacher relationships need to consider how TC changes by age and SES and give attention to school-level factors, in particular the student-teacher ratio. PMID- 28985420 TI - Effects of stem size on stem respiration and its flux components in yellow-poplar (Liriodendron tulipifera L.) trees. AB - Carbon dioxide (CO2) released from respiring cells in the stems of trees (RS) can diffuse radially to the atmosphere (EA) or dissolve in xylem sap and move internally in the tree (FT). Previous studies have observed that EA decreases as stem or branch diameter increases, but the cause of this relationship has not been determined, nor has the relationship been confirmed between stem diameter and RS, which includes both EA and FT. In this study, for the first time the mass balance technique was used to estimate RS of stems of Liriodendron tulipifera L. trees of different diameters, ranging from 16 to 60 cm, growing on the same site. The magnitude of the component fluxes scaled with tree size. Among the five trees, the contribution of EA to RS decreased linearly with increasing stem diameter and sapwood area while the contribution of FT to RS increased linearly with stem diameter and sapwood area. For the smallest tree EA was 86% of RS but it was only 46% of RS in the largest tree. As tree size increased a greater proportion of respired CO2 dissolved in sap and remained within the tree. Due to increase in FT with tree size, we observed that trees of different sizes had the same RS even though they had different EA. This appears to explain why the EA of stems and branches decreases as their size increases. PMID- 28985421 TI - Socioeconomic Condition and Prevalence of Malaria Fever in Pakistani Children: Findings from a Community Health Survey. AB - Objective: We assessed the prevalence of malarial fever and its association with demographic and socioeconomic factors in children <5 years of age. Methods: Using the data of Pakistan Demographic and Health Survey (PDHS), the socioeconomic condition (SEC) was assessed by using a household wealth index as a proxy indicator, generated through principal component analysis. Two-stage sampling was used for selection of households, and multilevel logistic regression analysis was performed. Results: The PDHS contains 10 935 children <5 years of age with valid information about malaria fever. In total, 36% (3930) children have malaria 2 weeks before the survey. A decreasing trend in prevalence of malaria fever was found with increasing SEC. Compared with SEC Quintile V, children of SEC Quintile I were more likely to get fever [adjusted odds ratio (AOR)=1.40 (1.15-1.69)] and of SEC Quintile II [AOR = 1.23 (1.03-1.45)]. Conclusion: SEC has a significant impact on the prevalence of malaria fever in the context of different regions in Pakistan. PMID- 28985418 TI - The SysteMHC Atlas project. AB - Mass spectrometry (MS)-based immunopeptidomics investigates the repertoire of peptides presented at the cell surface by major histocompatibility complex (MHC) molecules. The broad clinical relevance of MHC-associated peptides, e.g. in precision medicine, provides a strong rationale for the large-scale generation of immunopeptidomic datasets and recent developments in MS-based peptide analysis technologies now support the generation of the required data. Importantly, the availability of diverse immunopeptidomic datasets has resulted in an increasing need to standardize, store and exchange this type of data to enable better collaborations among researchers, to advance the field more efficiently and to establish quality measures required for the meaningful comparison of datasets. Here we present the SysteMHC Atlas (https://systemhcatlas.org), a public database that aims at collecting, organizing, sharing, visualizing and exploring immunopeptidomic data generated by MS. The Atlas includes raw mass spectrometer output files collected from several laboratories around the globe, a catalog of context-specific datasets of MHC class I and class II peptides, standardized MHC allele-specific peptide spectral libraries consisting of consensus spectra calculated from repeat measurements of the same peptide sequence, and links to other proteomics and immunology databases. The SysteMHC Atlas project was created and will be further expanded using a uniform and open computational pipeline that controls the quality of peptide identifications and peptide annotations. Thus, the SysteMHC Atlas disseminates quality controlled immunopeptidomic information to the public domain and serves as a community resource toward the generation of a high-quality comprehensive map of the human immunopeptidome and the support of consistent measurement of immunopeptidomic sample cohorts. PMID- 28985419 TI - Subthalamic nucleus stimulation impairs emotional conflict adaptation in Parkinson's disease. AB - The subthalamic nucleus (STN) occupies a strategic position in the motor network, slowing down responses in situations with conflicting perceptual input. Recent evidence suggests a role of the STN in emotion processing through strong connections with emotion recognition structures. As deep brain stimulation (DBS) of the STN in patients with Parkinson's disease (PD) inhibits monitoring of perceptual and value-based conflict, STN DBS may also interfere with emotional conflict processing. To assess a possible interference of STN DBS with emotional conflict processing, we used an emotional Stroop paradigm. Subjects categorized face stimuli according to their emotional expression while ignoring emotionally congruent or incongruent superimposed word labels. Eleven PD patients ON and OFF STN DBS and eleven age-matched healthy subjects conducted the task. We found conflict-induced response slowing in healthy controls and PD patients OFF DBS, but not ON DBS, suggesting STN DBS to decrease adaptation to within-trial conflict. OFF DBS, patients showed more conflict-induced slowing for negative conflict stimuli, which was diminished by STN DBS. Computational modelling of STN influence on conflict adaptation disclosed DBS to interfere via increased baseline activity. PMID- 28985423 TI - ANALYSIS OF URINARY EXCRETION DATA FROM THREE PLUTONIUM-CONTAMINATED WOUNDS AT LOS ALAMOS NATIONAL LABORATORY. AB - The National Council on Radiation Protection (NCRP)-156 Report proposes seven different biokinetic models for wound cases depending on the physicochemistry of the contaminant. Because the models were heavily based on experimental animal data, the authors of the report encouraged application and validation of the models using bioassay data from actual human exposures. Each of the wound models was applied to three plutonium-contaminated wounds, and the models resulted in a good agreement to only one of the cases. We then applied a simpler biokinetic model structure to the bioassay data and showed that fitting the transfer rates from this model structure yielded better agreement with the data than does the best-fitting NCRP-156 model. Because the biokinetics of radioactive material in each wound is different, it is impractical to propose a discrete set of model parameters to describe the biokinetics of radionuclides in all wounds, and thus each wound should be treated empirically. PMID- 28985422 TI - Relationship status and perceived support in the social regulation of neural responses to threat. AB - Strong social ties correspond with better health and well being, but the neural mechanisms linking social contact to health remain speculative. This study extends work on the social regulation of brain activity by supportive handholding in 110 participants (51 female) of diverse racial and socioeconomic origins. In addition to main effects of social regulation by handholding, we assessed the moderating effects of both perceived social support and relationship status (married, cohabiting, dating or platonic friends). Results suggest that, under threat of shock, handholding by familiar relational partners attenuates both subjective distress and activity in a network associated with salience, vigilance and regulatory self-control. Moreover, greater perceived social support corresponded with less brain activity in an extended network associated with similar processes, but only during partner handholding. In contrast, we did not observe any regulatory effects of handholding by strangers, and relationship status did not moderate the regulatory effects of partner handholding. These findings suggest that contact with a familiar relational partner is likely to attenuate subjective distress and a variety of neural responses associated with the presence of threat. This effect is likely enhanced by an individual's expectation of the availability of support from their wider social network. PMID- 28985424 TI - Influence of reproduction on nitrogen uptake and allocation to new organs in Fagus crenata. AB - The contributions of the internal nitrogen (N) cycle and N uptake from soil to growth in mature trees remain poorly understood, especially during reproduction. In order to elucidate how reproduction affects N uptake, allocation and remobilization, we applied pulse 15N labelling to three fruiting (F) and three non-fruiting (NF) Fagus crenata Blume trees after the leaves were fully unfurled. Three-year-old branches were sampled from upper crowns at about 2 week intervals until leaf fall. 15N content per organ dry mass (15Nexcess) and N concentration in all new shoot organs were determined. Fruiting led to greater 15Nexcess uptake from the soil during the first month following application. Cupules absorbed the highest fraction of 15Nexcess initially and nuts contained about half the 15Nexcess at the end of the growing season. Biomass of reproductive organs represented up to 70% of new shoot growth in F trees. This fruit burden led to 34% and 38% reduction in biomass and 15Nexcess, respectively, in mature leaves compared with NF trees. Moreover, the increment of 15Nexcess in new shoots of F relative to NF trees was lower than the increment of biomass between the two. These results indicate that N is a limiting resource during masting in F. crenata. 15Nexcess incorporated into nuts started to increase dramatically once 15Nexcess in leaves, branches and cupules hit seasonal maxima. Similar seasonal biomass growth patterns were also found in these organs, indicating that sink strength drives uptake and allocation of 15Nexcess between new shoot compartments. These results, together with translocation of 15Nexcess from cupules and senescing leaves to nuts (contributing to fruit ripening), suggest that a finely tuned growth phenology alleviated N limitation. Thus, fruiting did not influence the N concentration in leaves or branches. These reproduction related variations in N uptake and allocation among new shoot compartments have implications for N dynamics in the plant-soil system. PMID- 28985425 TI - Alcohol's effects on emotionally motivated attention, defensive reactivity and subjective anxiety during uncertain threats. AB - Developing a better understanding of how and under what circumstances alcohol affects the emotions, cognitions and neural functions that precede and contribute to dangerous behaviors during intoxication may help to reduce their occurrence. Alcohol intoxication has recently been shown to reduce defensive reactivity and anxiety more during uncertain vs certain threat. However, alcohol's effects on emotionally motivated attention to these threats are unknown. Alcohol may disrupt both affective response to and attentional processing of uncertain threats making intoxicated individuals less able to avoid dangerous and costly behaviors. To test this possibility, we examined the effects of a broad range of blood alcohol concentrations on 96 participants' sub-cortically mediated defensive reactivity (startle potentiation), retrospective subjective anxiety (self-report) and cortically assessed emotionally motivated attention (probe P3 event related potential) while they experienced visually cued uncertain and certain location electric shock threat. As predicted, alcohol decreased defensive reactivity and subjective anxiety more during uncertain vs certain threat. In a novel finding, alcohol dampened emotionally motivated attention during uncertain but not certain threat. This effect appeared independent of alcohol's effects on defensive reactivity and subjective anxiety. These results suggest that alcohol intoxication dampens processing of uncertain threats while leaving processing of certain threats intact. PMID- 28985426 TI - Physiological and transcriptional responses of Catalpa bungei to drought stress under sufficient- and deficient-nitrogen conditions. AB - Many semi-arid ecosystems are simultaneously limited by soil water and nitrogen (N). We conducted a greenhouse experiment to address how N availability impacts drought-resistant traits of Catalpa bungei C. A. Mey at the physiological and molecular level. A factorial design was used, consisting of sufficient-N and deficient-N combined with moderate drought and well-watered conditions. Seedling biomass and major root parameters were significantly suppressed by drought under the deficient-N condition, whereas N application mitigated the inhibiting effects of drought on root growth, particularly that of fine roots with a diameter <0.2 mm. Intrinsic water-use efficiency was promoted by N addition under both water conditions, whereas stable carbon isotope compositions (delta13C) was promoted by N addition only under the well-watered condition. Nitrogen application positively impacted drought adaptive responses including osmotic adjustment and homeostasis of reactive oxygen species, the content of free proline, soluble sugar and superoxide dismutase activity: all were increased upon drought under sufficient-N conditions but not under deficient-N conditions. The extent of abscisic acid (ABA) inducement upon drought was elevated by N application. Furthermore, an N dependent crosstalk between ABA, jasmonic acid and indole acetic acid at the biosynthesis level contributed to better drought acclimation. Moreover, the transcriptional level of most genes responsible for the ABA signal transduction pathway, and genes encoding the antioxidant enzymes and plasma membrane intrinsic proteins, are elevated upon drought only under sufficient-N addition. These observations confirmed at the molecular level that major adaptive responses to drought are dependent on sufficient N nutrition. Although N uptake was decreased under drought, N-use efficiency and transcription of most genes encoding N metabolism enzymes were elevated, demonstrating that active N metabolism positively contributed drought resistance and growth of C. bungei under sufficient-N conditions. PMID- 28985427 TI - Blastocystis Hominis and Chronic Abdominal Pain in Children: Is there an Association between Them? AB - Chronic abdominal pain has many etiologies, one of them being parasites. The aim of this study was to find an association between chronic abdominal pain in children and Blastocystis hominis (Bh). Clinical files of patients with Bh and functional abdominal pain were reviewed. A comparison was made between patients who showed an improvement of their symptoms and those who did not. Out of the 138 patients who had functional abdominal pain and Bh, 37 patients did not receive any treatment (26.8%), while 101 received it and were treated with different antimicrobial agents (73.2%); regarding the improvement of symptoms, a statistically significant difference (p < 0.001) was observed. Chronic abdominal pain in children has different etiologies; however, we have documented through this work that it is appropriate to provide antimicrobial treatment for patients with Bh and chronic abdominal pain. PMID- 28985429 TI - Prevention of mother to child transmission of HIV in Tanzania: assessing gender mainstreaming on paper and in practice. AB - Although gender mainstreaming has been long recognized as a strategy for addressing gender inequalities and associated negative health outcomes; its implementation has remained a challenge, even in the area of prevention of mother to child transmission of HIV (PMTCT). Despite recognition of gender in Tanzania's political arena and prioritization of PMTCT by the health sector, there is very little information on how well gender has been mainstreamed into National PMTCT guidelines and organizational practices at service delivery level. Using a case study methodology, we combined document review with key informant interviews to assess gender mainstreaming in PMTCT on paper and in practice in Tanzania. We reviewed PMTCT policy/strategy documents using the WHO's Gender Responsive Assessment Scale (GRAS). The scale differentiates between level 1 (gender unequal), 2 (gender blind), 3 (gender sensitive), 4 (gender specific), and 5 (gender transformative). Key informant interviews were also conducted with 26 leaders purposively sampled from three government health facilities in Mwanza city to understand their practices. The gender responsiveness of PMTCT policy/strategy documents varies, with some being at GRAS level 3 (gender sensitive) and others at GRAS level 4 (gender specific). Those which are gender sensitive indicate gender awareness, but no remedial action is developed; while those which are gender specific go beyond indicating how gender may hinder PMTCT to highlighting remedial measures, such as the promotion of couple counselling and testing for HIV. In addition, interviews on organizational processes and practices suggested that there has been little attention to the holistic integration of gender in the delivery of PMTCT services. The study has revealed limited integration of gender concerns in PMTCT policy documents. Similarly, health facility leader responses indicate perspectives and practices that pay little attention to the holistic integration of gender in the delivery PMTCT services. PMID- 28985428 TI - An RNA editing/dsRNA binding-independent gene regulatory mechanism of ADARs and its clinical implication in cancer. AB - Adenosine-to-inosine (A-to-I) RNA editing, catalyzed by Adenosine DeAminases acting on double-stranded RNA(dsRNA) (ADAR), occurs predominantly in the 3' untranslated regions (3'UTRs) of spliced mRNA. Here we uncover an unanticipated link between ADARs (ADAR1 and ADAR2) and the expression of target genes undergoing extensive 3'UTR editing. Using METTL7A (Methyltransferase Like 7A), a novel tumor suppressor gene with multiple editing sites at its 3'UTR, we demonstrate that its expression could be repressed by ADARs beyond their RNA editing and double-stranded RNA (dsRNA) binding functions. ADARs interact with Dicer to augment the processing of pre-miR-27a to mature miR-27a. Consequently, mature miR-27a targets the METTL7A 3'UTR to repress its expression level. In sum, our study unveils that the extensive 3'UTR editing of METTL7A is merely a footprint of ADAR binding, and there are a subset of target genes that are equivalently regulated by ADAR1 and ADAR2 through their non-canonical RNA editing and dsRNA binding-independent functions, albeit maybe less common. The functional significance of ADARs is much more diverse than previously appreciated and this gene regulatory function of ADARs is most likely to be of high biological importance beyond the best-studied editing function. This non-editing side of ADARs opens another door to target cancer. PMID- 28985430 TI - Reproductive investments driven by sex and altitude in sympatric Populus and Salix trees. AB - The sex ratios of co-existing Populus and Salix vary depending on altitude and species: 1:1 equlibrium sex ratios are observed at mid-altitude but skewed ones at high altitudes, where Populus shows male-biased and Salix female-biased sex ratios. However, the underlying ecological mechanisms are poorly known. Reproductive investments of Populus purdomii Rehd. and Salix magnifica Hemsl. were assessed at altitudes of 2000 and 2600 m in the Gongga Mountain by different metrics, including biomass, carbon (C), nitrogen (N) and phosphorus (P) concentrations and construction cost, and by estimating the payback time that combines energy gain and associated costs. Reproductive investment measured as C, N and P concentrations, and construction cost was higher in P. purdomii females at 2600 m. However, in S. magnifica, no difference was observed for biomass, C and N at 2600 m, but the investments for P and construction cost were even greater in males. The payback time showed no significant differences for the sexes at 2000 m, but it was shorter for P. purdomii males and S. magnifica females at 2600 m. We concluded that nutrient- and construction cost-based estimates of reproductive allocation can provide more informative insight into the cost of reproduction than does biomass, and together with the payback time they can supply an explanation for divergent sex ratios in Populus and Salix. Consequently, our results improve our understanding of the causes and consequences of sexual dimorphism in dioecious species. PMID- 28985431 TI - Growth rate reduction causes a decline in the annual incremental trunk growth in masting Fagus crenata trees. AB - Tree trunk annual increments are markedly reduced in mast years. There are two hypotheses that could explain the mechanism for this phenomenon: (1) a reduction in the duration of growth due to switching the resource allocation from somatic growth to seed production; (2) reduction of growth rate due to resources being shared between somatic growth and reproduction simultaneously. In this study, we aimed to test these hypotheses in Fagus crenata Blume from the point of view of resource allocation. The radial growth patterns in F. crenata during a year without reproduction (2014) and a masting year (2015) were monitored using a digital dendrometer. At the same time, shoot growth patterns were monitored by sampling branches from the top of the canopy. Data obtained using the digital dendrometer were fitted to a sigmoidal function, and the parameters of the function were evaluated with a hierarchal Bayesian approach; estimated parameters were used to represent the properties of trunk growth phenology. Trunk growth started synchronously just after leaf unfurling in both mass-fruiting (F15) and limited-fruiting (NF15) trees in 2014 and 2015. Reproduction reduced the growth rate in 2015. This was due to the resources being allocated for the development of cupules and for formation of relatively thick branches, both of which occurred simultaneously with trunk growth. There was no clear difference in the duration of radial growth between F15 and NF15 trees in the 2 years, although seed maturation started after trunk growth ceased. As a result, the annual trunk radius increment was reduced in the F15 trees in 2015. These results suggested that reduction of radial growth rate (Hypothesis 2) caused the reduction in annual trunk increment of reproducing trees of this species. PMID- 28985432 TI - Intra-annual dynamics of xylem growth in Pinus massoniana submitted to an experimental nitrogen addition in Central China. AB - In recent decades, anthropogenic activities have increased nitrogen (N) deposition in terrestrial ecosystems. This higher availability of N is expected to impact plant growth. However, the effects of N deposition on tree growth remain inconclusive due to the wide variability of experimental methods used. This study aimed to test the effect of short-term N addition on the intra-annual wood formation of Chinese red pine (Pinus massoniana Lamb.) in a warm-temperate forest of Central China. From 2013, solution containing 25 kg N ha-1 year-1 was applied monthly to the understory of experimental plots from April to December to double the current natural N deposition. Each week from March to December in 2014 and 2015, cambial activity and the timings and dynamics of xylem formation were monitored by collecting microcores from stems. Xylem formation lasted from March to November, producing an average of 19 and 33 cells for all studied trees in 2014 and 2015, respectively. No difference in xylem cell production was observed between control and N-treated trees. Moreover, N-treated trees had similar timings, rates and durations of xylem formation as control trees. These findings indicated that short-term N addition was unable to affect timings and dynamics of xylem formation in Chinese red pine of warm-temperate forest. PMID- 28985433 TI - THYROID PHANTOM MEASUREMENTS IN JOINT EURADOS-LLNL INTERCOMPARISON EXERCISE. AB - The European Radiation Dosimetry Group (EURADOS), in collaboration with Lawrence Livermore National Laboratory's (LLNL's) Thyroid Intercomparison Program (TRIP), conducted an intercomparison exercise consistent with the goals of EURADOS. In total, 35 in vivo radiobioassay facilities from 18 countries participated to evaluate the differences between the neck and thyroid phantoms specified in two standards issued by the American National Standards Institute. Radioiodine (125I and 131I) measurement results were compared to the traceable standard activity levels added to each phantom. Measurement data showed no statistically significant differences between normalized activity measurements of the thyroid phantom types (20 and 30 ml). Differences were noted between the laboratories that routinely participate in the radioiodine thyroid intercomparison program (TRIP participants) and laboratories that have not previously participated in TRIP. Evaluation of the reasons for these differences will require additional EURADOS-LLNL collaborations. Finally, the measurement data from this intercomparison was used with a designed intake scenario for intercomparison of dose evaluations. Results from the dose intercomparison will be presented in a subsequent article. PMID- 28985435 TI - Neonatal Outcome of Babies Born to Women 40 Years and over at the University Hospital of the West Indies 2012-2013. AB - Aim: This article aims to determine neonatal outcome of babies born to women >=40 years at the University Hospital of the West Indies. Methods: This was a matched retrospective cohort study looking at the outcome of all babies born to women >=40 years and control babies born to women aged 20-30 years at the University Hospital of the West Indies over a 2-year period. Maternal and neonatal demographic data and course of admission for admitted neonates were recorded. Descriptive analyses were performed. Results: One hundred and ninety-eight neonates were born to women >=40 years and 208 to their younger counterparts, M:F 1:1.2. There was no difference in the number of preterm or low birth weight infants, the number of neonates with a low 5 min Apgar score <7, the number of neonates admitted or the number of neonates who died between women >=40 years and their younger counterparts (p > 0.05). Conclusion: No difference in adverse neonatal outcome was noted between women >=40 years and their younger counterparts. PMID- 28985434 TI - Electrophysiological correlates of oxytocin-induced enhancement of social performance monitoring. AB - Altered performance monitoring has been demonstrated after administration of different pharmacological compounds and in various clinical populations, such as excessive neurophysiological responses to mistakes in anxiety disorders. Here, a novel social pharmacological approach was applied to investigate whether oxytocin administration (24 IU) enhances performance monitoring for errors that have negative consequences for another individual, so-called social mistakes. Healthy male volunteers (N = 24) participated in a placebo-controlled crossover design. EEG measures were obtained while pairs of participants performed a speeded choice reaction-time task in an individual and social context. Following oxytocin administration, error-related negativity amplitudes were increased for social compared with individual mistakes. This increase was not found in the placebo condition. No effects of oxytocin were present in the individual context. The current study shows that oxytocin enhances performance monitoring specifically for social mistakes. This outcome is in line with a presumed role for oxytocin in salience attribution to social cues and underlines its context-dependency. Combining these processes may thus open up new research avenues and advance our understanding of individual differences in performance monitoring and oxytocin responses from a social neurocognitive, pharmacological and clinical perspective. PMID- 28985436 TI - LC-MS-MS with Post-Column Reagent Addition for the Determination of Zolpidem and its Metabolite Zolpidem Phenyl-4-carboxylic Acid in Oral Fluid after a Single Dose. AB - A rapid, selective and sensitive LC-MS-MS method with a post-column addition of acetonitrile was developed and fully validated for the quantitative determination of zolpidem and its major metabolite, zolpidem phenyl-4-carboxylic acid (ZPCA), in oral fluid. Preliminary sample treatment was limited to a simple dilution of 1 mL oral fluid specimen aliquots with methanol. Chromatography was performed on a Capcell Pak C18 MGII column (250 * 2.0 mm, 5 MUm i.d., Shiseido, Tokyo, Japan) with isocratic elution using a water-acetonitrile mobile phase with 0.1% formic acid, 5% acetonitrile and 20 mM ammonium acetate in an aqueous phase at a flow rate of 0.4 mL/min. Acetonitrile was added post-column at a flow rate of 0.4 mL/min to enhance ionization of the analytes in the MS source. Detection was carried out on a QTrapTM 6500 mass spectrometer in positive ionization mode. Good linearities were generated over the range of 0.05-200 ng/mL for zolpidem and 0.1 200 ng/mL for ZPCA. Limit of detection for zolpidem and ZPCA were 0.01 ng/mL and 0.05 ng/mL, respectively, whereas LLOQs were 0.05 ng/mL and 0.1 ng/mL, respectively. This method meets the required criteria for bioanalytical analyses to be used for clinical and forensic purposes. Application of this method was demonstrated by testing authentic samples collected after a single oral dose to obtain insights into the general detectability and detection windows of zolpidem and ZPCA in oral fluid. PMID- 28985437 TI - The role of gamma interbrain synchrony in social coordination when humans face territorial threats. AB - Throughout history and into the modern era, human groups have been continually subjected to a wide range of societal threats, from natural disasters to pandemics to terrorism. Yet despite this fundamental aspect of human existence, there has been little research on how societal threat affects social coordination at both the neural and the behavioral level. Here, we show for the first time that individuals are better able to coordinate under high societal threat as compared to low or no threat (Experiment 1). Using a method of hyperscanning electroencephalography (EEG), which simultaneously measures brain activity among interacting subjects, we further illustrate that interbrain synchrony of gamma band oscillations is enhanced when people are under high threat, and increased gamma interbrain synchrony is associated with lower dyadic interpersonal time lag (i.e. higher coordination) (Experiment 2). To our knowledge, the current work provides some of the first empirical evidence that gamma interbrain synchrony is associated with social coordination when humans are under threat. PMID- 28985438 TI - Structural differences between glycosylated, disulfide-linked heterodimeric Knob into-Hole Fc fragment and its homodimeric Knob-Knob and Hole-Hole side products. AB - An increasing number of bispecific therapeutic antibodies are progressing through clinical development. The Knob-into-Hole (KiH) technology uses complementary mutations in the CH3 region of the antibody Fc fragment to achieve heavy chain heterodimerization. Here we describe the X-ray crystal structures of glycosylated and disulfide-engineered heterodimeric KiH Fc fragment and its homodimeric Knob Knob and Hole-Hole side products. The heterodimer structure confirms the KiH design principle and supports the hypothesis that glycosylation stabilizes a closed Fc conformation. Both homodimer structures show parallel Fc fragment architectures, in contrast to recently reported crystal structures of the corresponding aglycosylated Fc fragments which in the absence of disulfide mutations show an unexpected antiparallel arrangement. The glycosylated Knob-Knob Fc fragment is destabilized as indicated by variability in the relative orientation of its CH3 domains. The glycosylated Hole-Hole Fc fragment shows an unexpected intermolecular disulfide bond via the introduced Y349C Hole mutation which results in a large CH3 domain shift and a new CH3-CH3 interface. The crystal structures of glycosylated, disulfide-linked KiH Fc fragment and its Knob Knob and Hole-Hole side products reported here will facilitate further design of highly efficient antibody heterodimerization strategies. PMID- 28985439 TI - Identification of potential genes that contributed to the variation in the taxoid contents between two Taxus species (Taxus media and Taxus mairei). AB - Taxol is currently a valuable anticancer drug; however, the accumulated mixture of taxoids can vary greatly among Taxus species. So far, there is very little genomic information for the genus Taxus, except for Taxus baccata. Transcriptome analysis is a powerful approach to explore the different regulatory mechanisms underlying the taxoid biosynthesis pathway in Taxus species. First, we quantified the variation in the taxoid contents between Taxus media and Taxus mairei. The contents of paclitaxel and 10-deacetylpaclitaxel in T. media are higher than that in T. mairei. Then, the transcriptome profiles of T. media and T. mairei were analyzed to investigate the altered expressions. A total of 20,704 significantly differentially expressed genes (DEGs), including 9865 unigenes predominantly expressed in T. media and 10,839 unigenes predominantly expressed in T. mairei, were identified. In total, 120 jasmonic acid-related DEGs were analyzed, suggesting variations in 'response to JA stimulus' and 'JA biosynthetic process' pathways between T. media and T. mairei. Furthermore, a number of genes related to the precursor supply, taxane skeleton formation and hydroxylation, and C13 side chain assembly were also identified. The differential expression of the candidate genes involved in taxoid biosynthetic pathways may explain the variation in the taxoid contents between T. media and T. mairei. PMID- 28985440 TI - Mesothelioma incidence and asbestos exposure in Italian national priority contaminated sites. AB - Objectives This study aimed to (i) describe mesothelioma incidence in the Italian national priority contaminated sites (NPCS) on the basis of data available from the Italian National Mesothelioma Registry (ReNaM) and (ii) profile NPCS using Bayesian rank analysis. Methods Incident cases of mesothelioma and standardized incidence ratios (SIR) were estimated for both genders in each of the 39 selected NPCS in the period 2000-2011. Age-standardized rates of Italian geographical macro areas were used to estimate expected cases. Rankings of areas were produced by a hierarchical Bayesian model. Asbestos exposure modalities were discussed for each site. Results In the study period, 2683 incident cases of mesothelioma (1998 men, 685 women) were recorded. An excess of mesothelioma incidence was confirmed in sites with a known past history of direct use of asbestos (among men) such as Balangero (SIR 197.1, 95% CI 82.0-473.6), Casale Monferrato (SIR 910.7, 95% CI 816.5-1012.8), and Broni (SIR 1288.5, 95% CI 981.9-1691.0), in sites with shipyards and harbors (eg, Trieste, La Spezia, Venice, and Leghorn), and in settings without documented direct use of asbestos. The analysis ranked the sites of Broni and Casale Monferrato (both genders) and Biancavilla (only for women) the highest. Conclusions The present study confirms that asbestos pollution is a risk for people living in polluted areas, due to not only occupational exposure in industrial settings with direct use of asbestos but also the presence of asbestos in the environment. Epidemiological surveillance of asbestos-related diseases is a fundamental tool for monitoring the health profile in NPCS. PMID- 28985441 TI - Effects and associations of nutrition in patients with venous leg ulcers: A systematic review. AB - AIMS: To identify the associations and effects of nutritional characteristics and interventions on ulcer outcomes in adult patients with venous leg ulcers. BACKGROUND: Venous leg ulcers are the most prevalent type of lower limb ulcer; however, little evidence exists regarding the relationship between nutritional status and ulcer healing. DESIGN: A systematic search of English language articles was conducted using the Cochrane Collaboration Handbook for Systematic Reviews of Interventions. DATA SOURCES: A search of databases Ovid MEDLINE, EMBASE, Cochrane, CINAHL and Scopus was performed for studies published between January 2004 - May 2017. REVIEW METHODS: Quality of the included studies was assessed using the Cochrane Collaboration's Risk of Bias Assessment tool and the relevant Joanna Briggs Institute quality appraisal checklists. RESULTS: Twenty studies met the inclusion criteria. All participants had Clinical Aetiology Anatomy Pathophysiology classification C5 (healed) or C6 (active) ulcers. Studies were conducted in a range of clinical settings with relatively small sample sizes. The majority of patients were overweight or obese. Increased body mass index was associated with delayed wound healing. Vitamin D, folic acid and flavonoids were associated with some beneficial effects on ulcer healing. Dietary intakes of omega-3 fatty acids, vitamin C and zinc were low for some patients. CONCLUSION: Current evidence suggests that venous leg ulcer patients are more likely to be overweight or obese. However, evidence for weight management improving wound healing is lacking. Micronutrients, including vitamin D and folic acid, may improve wound healing in at-risk patients. PMID- 28985442 TI - Periodontal disease and pneumonia mortality in haemodialysis patients: A 7-year cohort study. AB - AIM: To evaluate the association between periodontal disease and pneumonia mortality in haemodialysis patients. MATERIALS AND METHODS: This prospective cohort study included 211 patients (mean age, 64.4 years) undergoing haemodialysis at a single medical centre. The patients underwent a baseline clinical dental examination in 2008 and were then followed up until July 2015. Periodontal disease was defined as the presence of clinical attachment loss of >=4 mm in >=30% of the probed sites. The primary endpoint, that is death from pneumonia, was determined by reviewing death certificates and was analysed using the competing-risks regression model. RESULTS: At baseline, 92 patients (43.6%) had periodontal disease. The median follow-up period was 84 months (interquartile range, 36-86 months). Of the 68 deaths that occurred, 21 were from pneumonia. The multivariable competing-risks regression model showed that periodontal disease was significantly associated with death from pneumonia (adjusted subhazard ratio, 3.49; 95% confidence interval, 1.14-10.64), after adjusting for other baseline health characteristics. CONCLUSIONS: The results of this study suggest that periodontal disease is independently associated with pneumonia mortality in haemodialysis patients. Future studies evaluating the potential effect of oral interventions for periodontal health improvement on pneumonia in haemodialysis patients would be of great interest. PMID- 28985444 TI - Synthesis of the Unknown Indeno[1,2-a]fluorene Regioisomer: Crystallographic Characterization of Its Dianion. AB - Of the five possible indenofluorene regioisomers, examples of a fully conjugated indeno[1,2-a]fluorene scaffold have so far remained elusive. This work reports the preparation and characterization of 7,12-dimesitylindeno[1,2-a]fluorene as a highly reactive species. Experimental and computational data support the notion of a molecule with pronounced diradical character that exists in a triplet ground state. As such, both NICS and ACID calculations suggest that the indeno[1,2 a]fluorene scaffold is weakly Baird aromatic. Reduction of the unstable red solid with Cs metal produces the dianion of the title compound, from which single crystals could be obtained and X-ray data acquired, thus fully corroborating the proposed indeno[1,2-a]fluorene hydrocarbon core. PMID- 28985445 TI - Physiological dissection revealed that both uptake and assimilation are the major components regulating different growth responses of two tobacco cultivars to nitrogen nutrition. AB - K326 and HD represent major tobacco cultivars in China, which required large N fertiliser input but at different application rates. To understand primary components affecting tobacco N use physiology, we adopted these two varieties as valuable genetic material to assess their growth response to N nutrition. We established a hydroponic culture system to grow plants supplied with different N regimes. Plant biomass, N, ammonium, nitrate, arginine, GS and NR activity, N transfer and use efficiency as well as root uptake were examined. Our data revealed the preference of K326 and HD to utilise nitrate or ammonium nitrate but not ammonium alone, with 2 mm N supply probably sufficient and economical to achieve good biomass production at the vegetative stage. Moreover, both varieties were very sensitive to ammonium, perhaps due to lack of or abnormal signalling related to nitrate and/or arginine rather than impairment of N acquisition and initial assimilation; this was supported by measurements of the plant content of N, ammonium and activities of GS and NR. Notably, short-term 15 N root influx studies identified differential uptake kinetics of K326 and HD, with distinct affinities and transport rates for ammonium and nitrate. The data suggest that the growth adaptation of K326 or HD to higher or lower N may be ascribed to different competences for effective N uptake/translocation and assimilation. Thus, our work provides valuable information to prompt deeper investigation of the molecular basis controlling plant N use efficiency. PMID- 28985446 TI - Preparation Ferrule Design Effect on Endocrown Failure Resistance. AB - PURPOSE: To evaluate the effect of preparation ferrule inclusion with fracture resistance of mandibular molar endocrowns. MATERIALS AND METHODS: Recently extracted mandibular third molars were randomly divided into 3 groups (n = 12) with the coronal tooth structure removed perpendicular to the root long axis approximately 2 mm above the cemento-enamel junction with a slow-speed diamond saw. The pulp chamber was exposed using a diamond bur in a high-speed handpiece with pulpal remnants removed and canals instrumented using endodontic hand instruments. The chamber floor was restored using a resin core material with a two-step, self-etch adhesive and photopolymerized with a visible light-curing unit to create a 2 mm endocrown preparation pulp chamber extension. One and two millimeter ferrule height groups were prepared using a diamond bur in a high speed handpiece following CAD/CAM guidelines. Completed preparation surface area was determined using a digital measuring microscope. Scanned preparations were restored with lithium disilicate restorations with a self-adhesive resin luting agent. All manufacturer recommendations were followed. Specimens were stored at 37 degrees C/98% humidity and tested to failure after 24 hours at a 45 degrees angle to the tooth long axis using a universal testing machine. Failure load was converted to MPa using the available bonding surface area with mean data analyzed using Kruskal-Wallis/Dunn (p = 0.05). RESULTS: Calculated failure stress found no difference in failure resistance among the three groups; however, failure load results identified that the endocrown preparations without ferrule had significantly lower fracture load resistance. Failure mode analysis identified that all preparations demonstrated a high number of catastrophic failures. CONCLUSIONS: Under the conditions of this study, ferrule-containing endocrown preparations demonstrated significantly greater failure loads than standard endocrown restorations; however, calculated failure stress based on available surface area for adhesive bonding found no difference between the groups. Lower instances of catastrophic failure were observed with the endocrown preparations containing 1 mm of preparation ferrule design; however, regardless of the presence of ferrule, this study found that all endocrown restorations suffered a high proportion of catastrophic failures but at loads greater than reported under normal masticatory function. PMID- 28985447 TI - Restoration contour is a risk indicator for peri-implantitis: A cross-sectional radiographic analysis. AB - AIM: The purpose of this study was to determine whether restoration emergence angle was associated with peri-implantitis. MATERIALS AND METHODS: A data set consisting of 96 patients with 225 implants (mean follow-up: 10.9 years) was utilized. Implants were divided into bone-level and tissue-level groups, and radiographs were analysed to determine the restoration emergence angles, as well as restoration profiles (convex or concave). Peri-implantitis was diagnosed based on probing depth and radiographic bone loss. Associations between peri implantitis and emergence angles/profiles were assessed using generalized estimating equations. RESULTS: Eighty-three patients with 168 implants met inclusion criteria. The prevalence of peri-implantitis was significantly greater in the bone-level group when the emergence angle was >30 degrees compared to an angle <=30 degrees (31.3% versus 15.1%, p = .04). In the tissue-level group, no such correlation was found. For bone-level implants, when a convex profile was combined with an angle of >30 degrees, the prevalence of peri-implantitis was 37.8% with a statistically significant interaction between emergence angle and profile (p = .003). CONCLUSIONS: Emergence angle of >30 degrees is a significant risk indicator for peri-implantitis and convex profile creates an additional risk for bone-level implants, but not for tissue-level implants. PMID- 28985448 TI - A Systematic Review of the Survival and Complication Rates of All-Ceramic Resin Bonded Fixed Dental Prostheses. AB - PURPOSE: The aim of this systematic review was to investigate the survival and complication rates of all-ceramic resin-bonded fixed dental prostheses (RBFDPs). MATERIALS AND METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were applied. A systematic search was conducted by an electronic search in PubMed, EMBASE, Cochrane Library, and CNKI databases complemented by a manual search. Only clinical studies on all-ceramic RBFDPs with a mean follow-up period of at least 3 years qualified for data analyses. RESULTS: Among 1503 screened articles, one randomized controlled trial (RCT) and seven prospective or retrospective cohort studies were included in this study. The estimated 5-year survival rate of all-ceramic RBFDPs was 91.2%. Debonding and framework fracture were the two most frequent technical complications, and the estimated 5-year debonding rate and fracture rate were 12.2% and 4.8%, respectively. Additionally, cantilevered all-ceramic RBFDPs had a higher survival rate (p < 0.01), lower debonding rate, (p < 0.05), and fracture rate (p < 0.01) compared with two-retainer all-ceramic RBFDPs. Zirconia ceramic RBFDPs had a lower incidence of failure but a higher debonding rate compared with glass ceramic RBFDPs (p < 0.01). CONCLUSION: Within the limitations of this systematic review, although all-ceramic RBFDPs have a favorable 5-year survival rate, this rate cannot represent the complete success of the treatment, since it may include typical complications such as debonding and fractures. There is an urgent need for long-term clinical studies, especially for well-designed RCTs on all-ceramic RBFDPs. PMID- 28985443 TI - KV channels and the regulation of vascular smooth muscle tone. AB - VSMCs in resistance arteries and arterioles express a diverse array of KV channels with members of the KV 1, KV 2 and KV 7 families being particularly important. Members of the KV channel family: (i) are highly expressed in VSMCs; (ii) are active at the resting membrane potential of VSMCs in vivo (-45 to -30 mV); (iii) contribute to the negative feedback regulation of VSMC membrane potential and myogenic tone; (iv) are activated by cAMP-related vasodilators, hydrogen sulfide and hydrogen peroxide; (v) are inhibited by increases in intracellular Ca2+ and vasoconstrictors that signal through Gq -coupled receptors; (vi) are involved in the proliferative phenotype of VSMCs; and (vii) are modulated by diseases such as hypertension, obesity, the metabolic syndrome and diabetes. Thus, KV channels participate in every aspect of the regulation of VSMC function in both health and disease. PMID- 28985449 TI - How does climate change affect regeneration of Mediterranean high-mountain plants? An integration and synthesis of current knowledge. AB - Mediterranean mountains are extraordinarily diverse and hold a high proportion of endemic plants, but they are particularly vulnerable to climate change, and most species distribution models project drastic changes in community composition. Retrospective studies and long-term monitoring also highlight that Mediterranean high-mountain plants are suffering severe range contractions. The aim of this work is to review the current knowledge of climate change impacts on the process of plant regeneration by seed in Mediterranean high-mountain plants, by combining available information from observational and experimental studies. We also discuss some processes that may provide resilience against changing environmental conditions and suggest some research priorities for the future. With some exceptions, there is still little evidence of the direct effects of climate change on pollination and reproductive success of Mediterranean high-mountain plants, and most works are observational and/or centred only in the post dispersal stages (germination and establishment). The great majority of studies agree that the characteristic summer drought and the extreme heatwaves, which are projected to be more intense in the future, are the most limiting factors for the regeneration process. However, there is an urgent need for studies combining elevational gradient approaches with experimental manipulations of temperature and drought to confirm the magnitude and variability of species' responses. There is also limited knowledge about the ability of Mediterranean high-mountain plants to cope with climate change through phenotypic plasticity and local adaptation processes. This could be achieved by performing common garden and reciprocal translocation experiments with species differing in life history traits. PMID- 28985450 TI - Patterns of periodontal disease progression based on linear mixed models of clinical attachment loss. AB - AIM: The goal of the present longitudinal cohort study was to examine patterns of periodontal disease progression at progressing sites and subjects defined based on linear mixed models (LMM) of clinical attachment loss (CAL). MATERIALS AND METHODS: A total of 113 periodontally healthy and 302 periodontitis subjects had their CAL calculated bimonthly for 12 months. LMMs were fitted for each site and the predicted CAL levels used to categorize their progression state. Participants were grouped based on the number of progressing sites into unchanged, transitional and active subjects. Patterns of periodontal disease progression were explored using descriptive statistics. RESULTS: Progression occurred primarily at molars (50% of progressing sites) and inter-proximal sites (72%), affected a higher proportion of deep than shallow sites (2.7% versus 0.7%), and pocketing was the main mode of progression (49%). We found a low level of agreement (47%) between the LMM and traditional approaches to determine progression such as change in CAL >=3 mm. Fourteen per cent of subjects were classified as active and among those 93% had periodontitis. The annual mean rate of progression for the active subjects was 0.35 mm/year. CONCLUSION: Progressing sites and subjects defined based on LMMs presented patterns of disease progression similar to those previously reported in the literature. PMID- 28985451 TI - Independent association among suicidal ideation, asthma, and bronchial hyperresponsiveness in adolescents. PMID- 28985452 TI - Synergistic Manganese(I) C-H Activation Catalysis in Continuous Flow: Chemoselective Hydroarylation. AB - Chemoselective hydroarylations were accomplished by a novel synergistic Bronsted acid/manganese(I)-catalyzed C-H activation manifold. Thus, alkynes bearing O leaving groups could, for the first time, be employed for C-H alkenylations without concurrent beta-O elimination, thereby setting the stage for versatile late-stage diversifications. Also described is the first manganese-catalyzed C-H activation in continuous flow, thus enabling efficient hydroarylations within only 20 minutes. PMID- 28985453 TI - Labelling Proteins with Carbon Nanodots. AB - We present efficient labelling of several proteins with orange-emissive carbon dots. N-Hydroxysuccinimide was used to activate the carboxyl groups of carbon dots, which subsequently reacted with the lysine groups present on the protein. Labelling was confirmed by UV absorption spectroscopy, PAGE and fluorescence correlation spectroscopy. Protein-conjugated carbon dots showed an enhancement in fluorescence lifetime and intensity owing to reduced intramolecular dynamic fluctuations. Single-molecule fluorescence measurements showed reduced fluorescence fluctuations and higher photon budget after protein tagging. Our study opens up opportunities to use carbon dots as highly precise biolabelling probes. PMID- 28985454 TI - Spectroscopic and Theoretical Characterization of Through-Space Conjugation of Foldamers with a Tetraphenylethene Hinge. AB - Through-space conjugation is an important noncovalent interaction in artificial materials and biomacromolecules. Establishing relationships between geometry and property is of high significance to provide deeper insights into this phenomenon. In this work, we have focused on the through-space conjugation in a new class of foldamers with a folded tetraphenylethene core. We have studied its impact on the photophysical properties through experimental measurements and theoretical calculations. It is found that the through-space conjugation makes significant contributions to the short-wavelength absorption in these foldamers. Moreover, these foldamers exhibit aggregation-enhanced emission (AEE) and apparent blue shifts in their emission spectra on going from solution to aggregates. The structural changes are smaller in the aggregated state than those in the isolated state during the excited-state relaxation process, which results in lower re organization energies. This accounts for the blueshifted and enhanced emissions in the aggregates. PMID- 28985456 TI - Successful treatment of childhood cheilitis granulomatosa with infliximab. PMID- 28985455 TI - Iridium Complexes with Proton-Responsive Azole-Type Ligands as Effective Catalysts for CO2 Hydrogenation. AB - Pentamethylcyclopentadienyl iridium (Cp*Ir) complexes with bidentate ligands consisting of a pyridine ring and an electron-rich diazole ring were prepared. Their catalytic activity toward CO2 hydrogenation in 2.0 m KHCO3 aqueous solutions (pH 8.5) at 50 degrees C, under 1.0 MPa CO2 /H2 (1:1) have been reported as an alternative to photo- and electrochemical CO2 reduction. Bidentate ligands incorporating an electron-rich diazole ring improved the catalytic performance of the Ir complexes compared to the bipyridine ligand. Complexes 2, 4, and 6, possessing both a hydroxy group and an uncoordinated NH group, which are proton-responsive and capable of generating pendent bases in basic media, recorded high initial turnover frequency values of 1300, 1550, and 2000 h-1 , respectively. Spectroscopic and computational investigations revealed that the reversible deprotonation changes the electronic properties of the complexes and causes interactions between pendent base and substrate and/or solvent water molecules, resulting in high catalytic performance in basic media. PMID- 28985457 TI - Periungual pyogenic granuloma-like lesions following plaster cast immobilization: a case managed with symptomatic therapy. PMID- 28985458 TI - Superior Blends Solid Polymer Electrolyte with Integrated Hierarchical Architectures for All-Solid-State Lithium-Ion Batteries. AB - Exploration of advanced solid electrolytes with good interfacial stability toward electrodes is a highly relevant research topic for all-solid-state batteries. Here, we report PCL/SN blends integrating with PAN-skeleton as solid polymer electrolyte prepared by a facile method. This polymer electrolyte with hierarchical architectures exhibits high ionic conductivity, large electrochemical windows, high degree flexibility, good flame-retardance ability, and thermal stability (workable at 80 degrees C). Additionally, it demonstrates superior compatibility and electrochemical stability toward metallic Li as well as LiFePO4 cathode. The electrolyte/electrode interfaces are very stable even subjected to 4.5 V at charging state for long time. The LiFePO4/Li all-solid state cells based on this electrolyte deliver high capacity, outstanding cycling stability, and superior rate capability better than those based on liquid electrolyte. This solid polymer electrolyte is eligible for next generation high energy density all-solid-state batteries. PMID- 28985459 TI - Regioisomeric Non-Fullerene Acceptors Containing Fluorobenzo[c][1,2,5]thiadiazole Unit for Polymer Solar Cells. AB - We designed and synthesized two isomeric nonfullerene acceptors, IFBR-p and IFBR d. These molecular semiconductors contain indacenodithiophene (IDT) as the central unit, adjacent asymmetric 5-fluorobenzo[c][1,2,5]thiadiazole units, and are flanked with rhodanine as the peripheral units. The orientation of the two fluorine atoms (proximal, p, or distal, d), relative to IDT impacts most severely the film morphologies when blended with the electron-donating polymer PTzBI. Polymer solar cells based on PTzBI:IFBR-p give rise to a power conversion efficiency (7.3 +/- 0.2%) that is higher than what is achieved with PTzBI:IFBR-d (5.2 +/- 0.1%). This difference is attributed to the lower tendency for (over)crystallization by IFBR-p and the resulting more favorable morphology of the photoactive layer. These results highlight the subtle impact of substitution regiochemistry on the properties of nonfullerene acceptors through modulation of their self-assembly tendencies. PMID- 28985460 TI - Plasmonic MoO2 Nanospheres as a Highly Sensitive and Stable Non-Noble Metal Substrate for Multicomponent Surface-Enhanced Raman Analysis. AB - Semiconductor-based surface-enhanced Raman spectroscopy is getting more and more attention because of its great price advantage. One of the biggest obstacles to the large-scale application of it is the poor stability. Here, we report that plasmonic MoO2 nanospheres can be used as a highly sensitive and stable semiconducting-substrate material for surface-enhanced Raman scattering (SERS). By using the MoO2 nanospheres as Raman substrates, a series of typical compounds with high attention can be accurately detected. This new non-noble metal substrate material shows a very high detection limit of 10-8 M, and exhibits great near-field enhancement with one of the highest enhancement factor of 4.8 * 106 reported to date. More importantly, the oxide with intermediate valence displays unexpected ultrahigh stability, which can withstand the corrosion of strong acid and strong alkali as well as 150 degrees C high temperature oxidation in air. Moreover, the accurate detection of multicomponent samples was also successful on this substrate. These results show that some simple metal oxides with intermediate valence may become sensitive and stable SERS substrate materials due to their abundant free electrons and structure that easily causes hot spots. PMID- 28985461 TI - Tuning Stilbene Photochemistry by Fluorination: State Reordering Leads to Sudden Polarization near the Franck-Condon Region. AB - Spontaneous polarization of a nonpolar molecule upon photoexcitation (the sudden polarization effect) earlier discussed for 90 degrees -twisted alkenes is observed and calculated for planar ring-fluorinated stilbenes, trans 2,3,5,6,2',3',5',6'-octofluorostilbene (tF2356) and trans 2,3,4,5,6,2',3',4',5',6'-decafluorostilbene (tF23456). Due to the fluorination, Franck-Condon states S1FC and S2FC are dominated by the quasi-degenerate HOMO-1 > LUMO and HOMO-2 -> LUMO excitations, while their interaction gives rise to a symmetry-broken zwitterionic S1 state. After optical excitation of tF2356, one observes an ultrafast (~0.06 ps) evolution that reflects relaxation from initial nonpolar S3FC to long-lived (1.3 ns in n-hexane and 3.4 ns in acetonitrile) polar S1. The polarity of S1 is evidenced by a solvatochromic shift of its fluorescence band. The experimental results provide a sensitive test for quantum-chemical calculations. In particular, our calculations agree with the experiment, and raise concerns about the applicability of the common TDDFT approach to relatively simple stilbenic systems. PMID- 28985462 TI - Reconceptualizing Fluorescence Correlation Spectroscopy for Monitoring and Analyzing Periodically Passing Objects. AB - Fluorescence correlation spectroscopy (FCS) is a sensitive technique commonly applied for studying the dynamics of nanoscale-labeled objects in solution. Current analysis of FCS data is largely based on the assumption that the labeled objects are stochastically displaced due to Brownian motion. However, this assumption is often invalid for microscale objects, since the motion of these objects is dominated by Stokes drag and settling or rising effects, rather than stochastic Brownian motion. To utilize the power of FCS for systems with nonstochastic displacements of objects, the collection and analysis of FCS data have to be reconceptualized. Here, we extended the applicability of FCS for the detection and analysis of periodically passing objects. Toward this end, we implemented droplet-based microfluidics, in which monodispersed droplets containing fluorescent marker are flowing equally spaced within microchannels. We show by simulations and experiments that FCS can sensitively quantify the flow rates, variability, and content of rapidly passing droplets. This information can be derived at high temporal resolution, based on the intensity fluctuations generated by only 5-10 passing droplets. Moreover, by utilizing the periodicity of the flowing droplets for noise reduction by averaging, FCS can monitor accurately the droplets flow even if their fluorescence intensity is negligible. Hence, extending FCS for periodically passing objects converts it into a powerful analytical tool for high-throughput droplet-based microfluidics. Moreover, based on the principles described here, FCS can be straightforwardly applied for a variety of systems in which the passing of objects is periodic rather than stochastic. PMID- 28985463 TI - Dopamine-Loaded Liposomes for in-Situ Amplified Photoelectrochemical Immunoassay of AFB1 to Enhance Photocurrent of Mn2+-Doped Zn3(OH)2V2O7 Nanobelts. AB - A novel signal-amplified strategy based on dopamine-loaded liposome (DLL) was developed for competitive-type nonenzymatic photoelectrochemical (PEC) immunoassay of small- molecular aflatoxin B1 (AFB1) in foodstuff, using Mn2+ doped Zn3(OH)2V2O7.2H2O nanobelts. The signal was amplified by high-loaded capacity of liposome and the highly efficient dopamine molecule to enhance photocurrent of Mn2+-doped Zn3(OH)2V2O7.2H2O nanobelts. The loaded dopamine in the liposome was used as an electron donor to scavenge the hole and inhibit the charge recombination. To design such an immunoassay system, a AFB1-bovine serum albumin (AFB1-BSA) conjugate was covalently bound with the multifunctional liposome via the cross-linkage glutaraldehyde, whereas monoclonal anti-AFB1 antibody was labeled onto a magnetic bead by typical carbodiimide coupling. Upon addition of target AFB1, a competitive immunoreaction was carried out between the analyte and the AFB1-BSA-DLL for the conjugated antibody on the magnetic bead. Followed by magnetic separation, the carried DLL on the magnetic bead was lysed by using Triton X-100 to release the encapsulated dopamine. The as-produced dopamine (as an elector donor) increased the photocurrent of the Mn2+-doped Zn3(OH)2V2O7.2H2O nanobelts. The photocurrent depended on the as-released amount of the dopamine. The change in the photocurrent enhanced with the increasing AFB1 concentration. Under the optimal conditions, Mn2+-doped Zn3(OH)2V2O7.2H2O nanobelts exhibited good photoelectrochemical responses for the detection of AFB1 and allowed the detection of AFB1 at a concentration as low as 0.3 pg mL-1 within a linear range from 0.5 pg mL-1 to 10 ng mL-1. Importantly, this system provided an ideal PEC immune sensing platform based on Mn2+-doped Zn3(OH)2V2O7.2H2O nanobelts and the high-loaded liposome for the detection of small molecules. PMID- 28985464 TI - Interfacial Self-Assembly of Polyelectrolyte-Capped Gold Nanoparticles. AB - We report on pH- and salt-responsive assembly of nanoparticles capped with polyelectrolytes at vapor-liquid interfaces. Two types of alkylthiol-terminated poly(acrylic acid) (PAAs, varying in length) are synthesized and used to functionalize gold nanoparticles (AuNPs) to mimic similar assembly effects of single-stranded DNA-capped AuNPs using synthetic polyelectrolytes. Using surface sensitive X-ray scattering techniques, including grazing incidence small-angle X ray scattering (GISAXS) and X-ray reflectivity (XRR), we demonstrate that PAA AuNPs spontaneously migrate to the vapor-liquid interfaces and form Gibbs monolayers by decreasing the pH of the suspension. The Gibbs monoalyers show chainlike structures of monoparticle thickness. The pH-induced self-assembly is attributed to the protonation of carboxyl groups and to hydrogen bonding between the neighboring PAA-AuNPs. In addition, we show that adding MgCl2 to PAA-AuNP suspensions also induces adsorption at the interface and that the high affinity between magnesium ions and carboxyl groups leads to two- and three-dimensional clusters that yield partial surface coverage and poorer ordering of NPs at the interface. We also examine the assembly of PAA-AuNPs in the presence of a positively charged Langmuir monolayer that promotes the attraction of the negatively charged capped NPs by electrostatic forces. Our results show that synthetic polyelectrolyte-functionalized nanoparticles exhibit interfacial self assembly behavior similar to that of DNA-functionalized nanoparticles, providing a pathway for nanoparticle assembly in general. PMID- 28985465 TI - Reversible Self-Assembly of Glutathione-Coated Gold Nanoparticle Clusters via pH Tunable Interactions. AB - Nanoparticle (NP) clusters with diameters ranging from 20 to 100 nm are reversibly assembled from 5 nm gold (Au) primary particles coated with glutathione (GSH) in aqueous solution as a function of pH in the range of 5.4 to 3.8. As the pH is lowered, the GSH surface ligands become partially zwitterionic and form interparticle hydrogen bonds that drive the self-limited assembly of metastable clusters in <1 min. Whereas clusters up to 20 nm in size are stable against cluster-cluster aggregation for up to 1 day, clusters up to 80 nm in size can be stabilized over this period via the addition of citrate to the solution in equal molarity with GSH molecules. The cluster diameter may be cycled reversibly by tuning pH to manipulate the colloidal interactions; however, modest background cluster-cluster aggregation occurs during cycling. Cluster sizes can be stabilized for at least 1 month via the addition of PEG-thiol as a grafted steric stabilizer, where PEG-grafted clusters dissociate back to starting primary NPs at pH 7 in fewer than 3 days. Whereas the presence of excess citrate has little effect on the initial size of the metastable clusters, it is necessary for both the cycling and dissociation to mediate the GSH-GSH hydrogen bonds. In summary, these metastable clusters exhibit significant characteristics of equilibrium self limited assembly between primary particles and clusters on time scales where cluster-cluster aggregation is not present. PMID- 28985467 TI - SERS Detection of Multiple Antimicrobial-Resistant Pathogens Using Nanosensors. AB - Successful pathogen detection is crucial for public health as the threat of infectious disease is dramatically increasing globally due to bacteria developing resistance to many antimicrobial drugs. The increase in bacterial infections has led to urgent demands for simpler, faster, and more reliable detection methods to be developed allowing the most appropriate therapy to be provided. Surface enhanced Raman scattering (SERS) is an analytical technique which has gained a great deal of interest for biosensing due to its sensitivity, selectivity, and multiplexing capabilities. A new bionanosensor has been developed for the isolation and detection of multiple bacterial pathogens via magnetic separation and SERS. This novel assay format involves using lectin functionalized magnetic nanoparticles for capture and isolation of bacteria from the sample matrix followed by specifically detecting bacterial pathogens using SERS active nanoparticles functionalized with antibodies which are strain specific. Therefore, the sample is captured using a "magnetic plug" and interrogated with a laser allowing simple and fast optical detection. Three bacterial pathogens (Escherichia coli, Salmonella typhimurium, and methicillin-resistant Staphylococcus aureus) were successfully isolated and detected, with the lowest concentration for each of the strains detected at just 101 colony forming units per mL (CFU/mL). In addition to single pathogen detection, a mixture of all three bacterial strains was isolated and identified within the same sample matrix using SERS with the triplex detection also being confirmed using principal component analysis. Herein, we demonstrate that this multiplexed bionanosensor is capable of providing rapid and sensitive discrimination of bacterial pathogens both individually, and within a multiplex system, offering opportunities for future point of care devices and advancements in biomedical applications. PMID- 28985466 TI - Charge Induced Dynamics of Water in a Graphene-Mica Slit Pore. AB - We use atomic force microscopy to in situ investigate the dynamic behavior of confined water at the interface between graphene and mica. The graphene is either uncharged, negatively charged, or positively charged. At high humidity, a third water layer will intercalate between graphene and mica. When graphene is negatively charged, the interface fills faster with a complete three layer water film, compared to uncharged graphene. As charged positively, the third water layer dewets the interface, either by evaporation into the ambient or by the formation of three-dimensional droplets under the graphene, on top of the bilayer. Our experimental findings reveal novel phenomena of water at the nanoscale, which are interesting from a fundamental point of view and demonstrate the direct control over the wetting properties of the graphene/water interface. PMID- 28985468 TI - Charge Transfer Exciton and Spin Flipping at Organic-Transition-Metal Dichalcogenide Interfaces. AB - Two-dimensional transition-metal dichalcogenides (TMD) can be combined with other materials such as organic small molecules to form hybrid van der Waals heterostructures. Because of different properties possessed by these two materials, the hybrid interface can exhibit properties that cannot be found in either of the materials. In this work, the zinc phthalocyanine (ZnPc)-molybdenum disulfide (MoS2) interface is used as a model system to study the charge transfer at these interfaces. It is found that the optically excited singlet exciton in ZnPc transfers its electron to MoS2 in 80 fs after photoexcitation to form a charge transfer exciton. However, back electron transfer occurs on the time scale of ~1-100 ps, which results in the formation of a triplet exciton in the ZnPc layer. This relatively fast singlet-triplet transition is feasible because of the large singlet-triplet splitting in organic materials and the strong spin-orbit coupling in TMD crystals. The back electron transfer would reduce the yield of free carrier generation at the heterojunction if it is not avoided. On the other hand, the spin-selective back electron transfer could be used to manipulate electron spin in hybrid electronic devices. PMID- 28985470 TI - Analysis of a Polystyrene-Toluene System through "Dynamic" Sorption Tests: Glass Transitions and Retrograde Vitrification. AB - Exposing a glassy polymer to a fluid phase (in gaseous or liquid state) containing a low molecular weight compound results in the sorption of the latter within the polymer, inducing, among other effects, the plasticization of the material which also promotes a change in the glass transition temperature. The amount of sorbed penetrant is often related in a complex fashion to the temperature and pressure of the fluid, thus determining that the locus of glass transition, when represented in pressure-temperature coordinates, may display as well rather complex patterns. This is an issue of particular importance in several applications of glassy polymers. In particular, we investigated the behavior of polystyrene in contact with toluene vapor by performing several modes of dynamic sorption experiments, in which the rate of change of the temperature of the system and/or of the pressure of the vapor phase are controlled with high accuracy, with the aim of creating a map of rubbery and glassy states of the polymer as a function of temperature and pressure of the toluene vapor. Isothermal tests were performed by changing the pressure at a controlled rate, isobaric tests were performed by changing the temperature at a controlled rate, and isoactivity tests were performed by concurrently changing, in a proper way, both temperature and pressure. A relevant feature resulting from these experiments is the presence of a discontinuity in the slope of the mass of toluene sorbed within polystyrene reported as a function of temperature and/or pressure. This discontinuity has been interpreted as the indication of the occurrence of a glass transition. The elaboration of the experimental results allowed identification of the pressure/temperature conditions at which rubbery or glassy states of the polymer mixture are established. Quite interestingly, the system displays the so- called "retrograde vitrification" phenomenon, which consists of the occurrence of a rubbery-to-glassy state transition as the temperature increases at a fixed pressure. The whole set of results has been successfully interpreted on the basis of thermodynamics of II order transitions accounting for the fact that experimental evidence of such transitions is significantly affected by the kinetics of polymer relaxation. PMID- 28985469 TI - Programmed Cell Death Protein Ligand-1 Silencing with Polyethylenimine-Dermatan Sulfate Complex for Dual Inhibition of Melanoma Growth. AB - Programmed cell death protein-1 (PD-1) is a prominent immune checkpoint receptor interacting with its ligand, programmed cell death protein ligand-1 (PD-L1, B7 H1). The PD-1/PD-L1 interaction induces functional exhaustion of tumor-reactive cytotoxic T cells and, thus, interferes with antitumor T-cell immunity. In addition, PD-1/PD-L1 interaction promotes tumorigenesis via the mTOR signaling pathway in a group of cancers including melanoma. Based on the dual functions of PD-1/PD-L1 interactions in tumor progression, we hypothesize that siRNA targeting PD-L1 (siPD-L1) will suppress melanoma growth, acting on both immune checkpoint and intrinsic tumorigenesis pathways. We tested this hypothesis by delivering siPD-L1 with a polymeric carrier ("pd") consisting of disulfide-cross-linked polyethylenimine (CLPEI) and dermatan sulfate (DS), which we previously found to have a specific interaction with CD146-positive B16F10 melanoma cells. The siPD L1/pd suppressed the expression of PD-L1 in the interferon-gamma (IFN-gamma) challenged B16F10 melanoma cells in a cell-type dependent manner and attenuated the expression of tumor-specific genes in B16F10 cells. siPD-L1/pd suppressed the B16F10 melanoma growth in C57BL/6 immune-competent mice with increased tumor specific immunity. siPD-L1/pd also suppressed melanoma growth in immune compromised nude mice. Both animals showed a positive correlation between PD-L1 and p-S6k (a marker of mTOR pathway activation) expression in tumors. These results indicate that the siPD-L1/pd complex attenuates melanoma growth in both T cell-dependent and independent mechanisms. PMID- 28985471 TI - Reproducible Preparation of Proteopolymersomes via Sequential Polymer Film Hydration and Membrane Protein Reconstitution. AB - Film rehydration method is commonly used for membrane protein (MP) reconstitution into block copolymer (BCP), but the lack of control in the rehydration step formed a heterogeneous population of proteopolymersomes that interferes with the characterization and performance of devices incorporating them. To improve the self-assembly of polymersomes with simultaneous MP reconstitution, the study reported herein aimed to understand the effects of different variants of the rehydration procedure on the MP reconstitution into BCP membranes. The model MP used in this study was AquaporinZ (AqpZ), an alpha-helical MP that has been shown to have a high permeation rate exclusive to water molecules. Comparing four rehydration methods differing in the hydration time (i.e., brief wetting or full hydration) and medium (i.e., in buffer or AqpZ stock solution), prehydration with buffer prior to adding AqpZ was found to be most desirable and reproducible reconstitution method because it gave rise to the highest proportion of well formed vesicles with intact AqpZ functionality as evidenced by the transmission electron microscopy images, dynamic light scattering, and stopped-flow analyses. The mechanisms by which effective AqpZ reconstitution takes place were also investigated and discussed. Small-angle X-ray scattering analysis shows that hydrating the initially dry multilamellar BCP films allows the separation of lamellae. This is anticipated to increase the membrane fluidity that facilitates a fast and spontaneous integration of AqpZ as the detergent concentration is considerably lowered below its critical micelle concentration. Dilution of detergent can result in precipitation of proteins in the absence of well fluidized membranes for protein integration that underscores the importance of membrane fluidity in MP reconstitution. PMID- 28985472 TI - Degradation of Bisphenol A by Peroxymonosulfate Catalytically Activated with Mn1.8Fe1.2O4 Nanospheres: Synergism between Mn and Fe. AB - A high-efficient, low-cost, and eco-friendly catalyst is highly desired to activate peroxides for environmental remediation. Due to the potential synergistic effect between bimetallic oxides' two different metal cations, these oxides exhibit superior performance in the catalytic activation of peroxymonosulfate (PMS). In this work, novel Mn1.8Fe1.2O4 nanospheres were synthesized and used to activate PMS for the degradation of bisphenol A (BPA), a typical refractory pollutant. The catalytic performance of the Mn1.8Fe1.2O4 nanospheres was substantially greater than that of the Mn/Fe monometallic oxides and remained efficient in a wide pH range from 4 to 10. More importantly, a synergistic effect between solid-state Mn and Fe was identified in control experiments with Mn3O4 and Fe3O4. Mn was inferred to be the primary active site in the surface of the Mn1.8Fe1.2O4 nanospheres, while Fe(III) was found to play a key role in the synergism with Mn by acting as the main adsorption site for the reaction substrates. Both sulfate and hydroxyl radicals were generated in the PMS activation process. The intermediates of BPA degradation were identified and the degradation pathways were proposed. This work is expected to help to elucidate the rational design and efficient synthesis of bimetallic materials for PMS activation. PMID- 28985473 TI - Red Clover Aryl Hydrocarbon Receptor (AhR) and Estrogen Receptor (ER) Agonists Enhance Genotoxic Estrogen Metabolism. AB - Many women consider botanical dietary supplements (BDSs) as safe alternatives to hormone therapy for menopausal symptoms. However, the effect of BDSs on breast cancer risk is largely unknown. In the estrogen chemical carcinogenesis pathway, P450 1B1 metabolizes estrogens to 4-hydroxylated catechols, which are oxidized to genotoxic quinones that initiate and promote breast cancer. In contrast, P450 1A1 catalyzed 2-hydroxylation represents a detoxification pathway. The current study evaluated the effects of red clover, a popular BDS used for women's health, and its isoflavones, biochanin A (BA), formononetin (FN), genistein (GN), and daidzein (DZ), on estrogen metabolism. The methoxy estrogen metabolites (2-MeOE1, 4-MeOE1) were measured by LC-MS/MS, and CYP1A1 and CYP1B1 gene expression was analyzed by qPCR. Nonmalignant ER-negative breast epithelial cells (MCF-10A) and ER-positive breast cancer cells (MCF-7) were derived from normal breast epithelial tissue and ER+ breast cancer tissue. Red clover extract (RCE, 10 MUg/mL) and isoflavones had no effect on estrogen metabolism in MCF-10A cells. However, in MCF-7 cells, RCE treatments downregulated CYP1A1 expression and enhanced genotoxic metabolism (4-MeOE1/CYP1B1 > 2-MeOE1/CYP1A1). Experiments with the isoflavones showed that the AhR agonists (BA, FN) preferentially induced CYP1B1 expression as well as 4-MeOE1. In contrast, the ER agonists (GN, DZ) downregulated CYP1A1 expression likely through an epigenetic mechanism. Finally, the ER antagonist ICI 182,780 potentiated isoflavone-induced XRE-luciferase reporter activity and reversed GN and DZ induced downregulation of CYP1A1 expression. Overall, these studies show that red clover and its isoflavones have differential effects on estrogen metabolism in "normal" vs breast cancer cells. In breast cancer cells, the AhR agonists stimulate genotoxic metabolism, and the ER agonists downregulate the detoxification pathway. These data may suggest that especially breast cancer patients should avoid red clover and isoflavone based BDSs when making choices for menopausal symptom relief. PMID- 28985474 TI - Erratum. PMID- 28985475 TI - Erratum. AB - In the article "Changes in Aerobic Plate and Escherichia coli-Coliform Counts and in Populations of Inoculated Foodborne Pathogens on Inshell Walnuts during Storage" by J. C. Frelka, G. R. Davidson, and L. J. Harris, Journal of Food Protection 79(7):1143-1153, 2016, doi:10.4315/0362-028X.JFP-15-553, the sentence beginning in line 11 of the Abstract should read as follows: "Populations declined by 2.86, 5.01, and 4.40 log CFU per nut for Salmonella, E. coli O157:H7, and L. monocytogenes, respectively, after drying and during the first 8 days of storage. PMID- 28985476 TI - In silico analysis of coevolution among ERMES proteins, Pex11, and Lam6. AB - In eukaryotic cells, communication and dynamic interactions among different organelles are important for maintaining cellular homeostasis. The endoplasmic reticulum (ER) mitochondria encounter structure (ERMES) complex establishes membrane contact sites between ER and mitochondria and is essential for phospholipid transport, protein import, and mitochondrial dynamics and inheritance. In this work, in silico analyses were used to probe the intramolecular interactions in ERMES proteins and the interactions that support the ERMES complex. Based on mutual information (MI), sites of intramolecular coevolution are predicted in the core proteins Mmm1, Mdm10, Mdm12, Mdm34, the peroxisomal protein Pex11, and cytoplasmic Lam6; these sites are linked to structural features of the proteins. Intermolecular coevolution is predicted among the synaptotagmin-like mitochondrial lipid-binding protein (SMP) domains of Mmm1, Mdm12, and Mdm34. Segments of Pex11 and Lam6 also share MI with the SMP domains of Mmm1 and Mdm12 and with the N terminus of Mdm34, implicating Mdm34 as part of a hub for interactions between ERMES and other complexes. In contrast, evidence of limited intermolecular coevolution involving the outer membrane protein Mdm10 was detected only with Mmm1 and Pex11. The results support models for the organization of these interacting proteins and suggest roles for Pex11 and Lam6 in regulating complex formation. PMID- 28985477 TI - Air velocity influences thermoregulation and endurance exercise capacity in the heat. AB - This study examined the effects of variations in air velocity on time to exhaustion and thermoregulatory and perceptual responses to exercise in a hot environment. Eight male volunteers completed stationary cycle exercise trials at 70% peak oxygen uptake until exhaustion in an environmental chamber maintained at 30 degrees C and 50% relative humidity. Four air velocity conditions, 30, 20, 10, and 0 km/h, were tested, and the headwind was directed at the frontal aspect of the subject by 2 industrial fans, with blade diameters of 1 m and 0.5 m, set in series and positioned 3 m from the subject's chest. Mean +/- SD time to exhaustion was 90 +/- 17, 73 +/- 16, 58 +/- 13, and 41 +/- 10 min in 30-, 20-, 10 , and 0-km/h trials, respectively, and was different between all trials (P < 0.05). There were progressive elevations in the rate of core temperature rise, mean skin temperature, and perceived thermal sensation as airflow decreases (P < 0.05). Core temperature, heart rate, cutaneous vascular conductance, and perceived exertion were higher and evaporative heat loss was lower without airflow than at any given airflow (P < 0.05). Dry heat loss and plasma volume were similar between trials (P > 0.05). The present study demonstrated a progressive reduction in time to exhaustion as air velocity decreases. This response is associated with a faster rate of core temperature rise and a higher skin temperature and perceived thermal stress with decreasing airflow. Moreover, airflow greater than 10 km/h (2.8 m/s) might contribute to enhancing endurance exercise capacity and reducing thermoregulatory, cardiovascular, and perceptual strain during exercise in a hot environment. PMID- 28985478 TI - Alteration of RNA Splicing by Small-Molecule Inhibitors of the Interaction between NHP2L1 and U4. AB - Splicing is an important eukaryotic mechanism for expanding the transcriptome and proteome, influencing a number of biological processes. Understanding its regulation and identifying small molecules that modulate this process remain a challenge. We developed an assay based on time-resolved fluorescence resonance energy transfer (TR-FRET) to detect the interaction between the protein NHP2L1 and U4 RNA, which are two key components of the spliceosome. We used this assay to identify small molecules that interfere with this interaction in a high throughput screening (HTS) campaign. Topotecan and other camptothecin derivatives were among the top hits. We confirmed that topotecan disrupts the interaction between NHP2L1 and U4 by binding to U4 and inhibits RNA splicing. Our data reveal new functions of known drugs that could facilitate the development of therapeutic strategies to modify splicing and alter gene function. PMID- 28985479 TI - Mechanical Ventilation in Adults with Acute Respiratory Distress Syndrome. Summary of the Experimental Evidence for the Clinical Practice Guideline. AB - RATIONALE: The American Thoracic Society/European Society for Intensive Care Medicine/Society of Critical Care Medicine guidelines on mechanical ventilation in adult patients with acute respiratory distress syndrome (ARDS) provide treatment recommendations derived from a thorough analysis of the clinical evidence on six clinical interventions. However, each of the recommendations contains areas of uncertainty and controversy, which may affect their appropriate clinical application. OBJECTIVES: To provide a critical review of the experimental evidence surrounding the pathophysiology of ventilator-induced lung injury and to help clinicians apply the clinical recommendations to individual patients. METHODS: We conducted a literature search and narrative review. RESULTS: A large number of experimental studies have been performed with the aim of improving understanding of the pathophysiological effects of mechanical ventilation. These studies have formed the basis for the design of many clinical trials. Translational research has fundamentally advanced understanding of the mechanisms of ventilator-induced lung injury, thus informing the design of interventions that improve survival in patients with ARDS. CONCLUSIONS: Because daily management of patients with ARDS presents the challenge of competing considerations, clinicians should consider the mechanism of ventilator-induced lung injury, as well as the rationale for interventions designed to mitigate it, when applying evidence-based recommendations at the bedside. PMID- 28985480 TI - Performance and Ratings Based Measures of Executive Function in School-Aged Children with Down Syndrome. AB - : We examined performance-based laboratory tasks and ratings-based assessments of executive function (EF) in school-aged children with Down syndrome and mental-age matched peers along with adaptive functioning. METHODS: A battery of assessments including EF laboratory tasks was collected. RESULTS: The DS group performed both working memory/inhibition and planning laboratory tasks with significant challenges. Moderate correlations were evident only between some laboratory tasks and ratings-based EF domains. However, ratings-based EF better predicted adaptive function than performance on an EF laboratory-based task. CONCLUSIONS: Findings underscore the need to address early and targeted EF intervention in children with DS. PMID- 28985481 TI - Determination of quantitative retention-activity relationships between pharmacokinetic parameters and biological effectiveness fingerprints of Salvia miltiorrhiza constituents using biopartitioning and microemulsion high performance liquid chromatography. AB - In this study, we analyzed danshen (Salvia miltiorrhiza) constituents using biopartitioning and microemulsion high-performance liquid chromatography (MELC). The quantitative retention-activity relationships (QRARs) of the constituents were established to model their pharmacokinetic (PK) parameters and chromatographic retention data, and generate their biological effectiveness fingerprints. A high-performance liquid chromatography (HPLC) method was established to determine the abundance of the extracted danshen constituents, such as sodium danshensu, rosmarinic acid, salvianolic acid B, protocatechuic aldehyde, cryptotanshinone, and tanshinone IIA. And another HPLC protocol was established to determine the abundance of those constituents in rat plasma samples. An experimental model was built in Sprague Dawley (SD) rats, and calculated the corresponding PK parameterst with 3P97 software package. Thirty five model drugs were selected to test the PK parameter prediction capacities of the various MELC systems and to optimize the chromatographic protocols. QRARs and generated PK fingerprints were established. The test included water/oil-soluble danshen constituents and the prediction capacity of the regression model was validated. The results showed that the model had good predictability. PMID- 28985482 TI - Magnetic graphene dispersive solid phase extraction-ultra performance liquid chromatography tandem mass spectrometry for determination of beta-agonists in urine. AB - In this study, a magnetic graphene-based dispersive solid phase extraction method was first developed for extraction of beta-agonists in urine. During the experiments, the absorbent amount, sample pH, extraction time, elution solution and elution time were optimized respectively. The optimized extraction method was finished within 10min, and showed high enrichment factors for 9 beta-agonists (20 26 folds). Furthermore, this absorbent could be reused for at least 60 times. Then this extraction method was combined with ultra performance liquid chromatography triple quadrupole tandem mass spectrometry to determine the 9 drugs in urine. The limits of detection for the 9 drugs were in a range of 0.015 0.023ngmL-1, and the recoveries from the standards fortified blank urine were in a range of 60.2%-109.4%. Therefore, this method could be used as a simple, rapid, sensitive and accurate tool to determine trace level of beta-agonists in urine. PMID- 28985483 TI - Pipette tip dummy molecularly imprinted solid-phase extraction of Bisphenol A from urine samples and analysis by gas chromatography coupled to mass spectrometry. AB - Molecularly imprinted polymers (MIPs) were synthesized and used as sorbent for Bisphenol A (BPA) pipette tip solid-phase microextraction from urine samples and BPA analysis by gas chromatography coupled to mass spectrometry (GC-MS). The MIPs were synthesized by the sol-gel methodology. Aminopropyltriethoxysilane (APTES) and tetraethyl orthosilicate (TEOS) were used as functional monomer and cross linking reagent, respectively. BPA and tetrabromobisphenol A (TBBPA) were evaluated as template during MIP synthesis. The BPA-based MIP displayed slightly higher extraction efficiency than the TBBPA-based dummy molecularly imprinted polymer (DMIP), but the TBBPA-based DMIP was selected as sorbent to minimize interference from leaked template. Comparison of the TBBPA-based DMIP, BPA-based MIP, and non-imprinted polymer (NIP) extraction efficiencies attested that the TBBPA-based DMIP was selective. The synthesized polymers were characterized by Scanning Electron Microscopy (SEM) and Fourier Transform Infrared spectroscopy (FTIR). The TBBPA-based DMIP was reused for over 100 times, which confirmed its robustness. The developed method was linear from 50 to 500ngmL-1. Precision values had coefficient of variation (CV) ranging from 4 to 14%. The accuracy relative standard deviation values (RSD) varied from -13.6 to 12.3%. PMID- 28985484 TI - An improved method for fast and selective separation of carotenoids by LC-MS. AB - Carotenoids are a large class of compounds that are biosynthesized by condensation of isoprene units in plants, fungi, bacteria, and some animals. They are characteristically highly conjugated through double bonds, which lead to many isomers as well susceptibility to oxidation and other chemical modifications. Carotenoids are important because of their potent antioxidant activity and are the pigments responsible for color in a wide variety of foods. Human consumption is correlated to many health benefits including prevention of cancer, cardiovascular disease, and age-related disease. Extreme hydrophobicity, poor stability, and low concentration in biological samples make these compounds difficult to analyze and difficult to develop analytical methods for aimed towards identification and quantification. Examples in the literature frequently report the use of exotic stationary phases, solvents, and additives, such as ethyl acetate, dichloromethane, and methyl tert-butyl ether that are incompatible with liquid chromatography mass spectrometry (LC-MS). In order to address these issues, we implemented the use of LC-MS friendly conditions using a low hydrophobicity cyano-propyl column (Agilent Zorbax SB-CN). We successfully differentiated between isomeric carotenoids by optimizing two gradient methods and using a mixture of 11 standards and LC-MS in positive ionization mode. Three complex biological samples from strawberry leaf, chicken feed supplement, and the photosynthetic bacterium Chloroflexus aurantiacus were analyzed and several carotenoids were resolved in these diverse backgrounds. Our results show this methodology is a significant improvement over other alternatives for analyzing carotenoids because of its ease of use, rapid analysis time, high selectivity, and, most importantly, its compatibility with typical LC-MS conditions. PMID- 28985485 TI - Assessment of in vivo organ-uptake and in silico prediction of CYP mediated metabolism of DA-Phen, a new dopaminergic agent. AB - The drug development process strives to predict metabolic fate of a drug candidate, together with its uptake in major organs, whether they act as target, deposit or metabolism sites, to the aim of establish a relationship between the pharmacodynamics and the pharmacokinetics and highlight the potential toxicity of the drug candidate. The present study was aimed at evaluating the in vivo uptake of 2-Amino-N-[2-(3,4-dihydroxy-phenyl)-ethyl]-3-phenyl-propionamide (DA-Phen) - a new dopaminergic neurotransmission modulator, in target and non-target organs of animal subjects and integrating these data with SMARTCyp results, an in silico method that predicts the sites of cytochrome P450-mediated metabolism of drug like molecules. Wistar rats, subjected to two different behavioural studies in which DA-Phen was intraperitoneally administrated at a dose equal to 0.03mmol/kg, were sacrificed after the experimental protocols and their major organs were analysed to quantify the drug uptake. The data obtained were integrated with in silico prediction of potential metabolites of DA-Phen using the SmartCYP predictive tool. DA-Phen reached quantitatively the Central Nervous System and the results showed that the amide bond of the DA-Phen is scarcely hydrolysed as it was found intact in analyzed organs. As a consequence, it is possible to assume that DA-Phen acts as dopaminergic modulator per se and not as a Dopamine prodrug, thus avoiding peripheral release and toxic side effects due to the endogenous neurotransmitter. Furthermore the identification of potential metabolites related to biotransformation of the drug candidate leads to a more careful evaluation of the appropriate route of administration for future intended therapeutic aims and potential translation into clinical studies. PMID- 28985486 TI - The effect of ankle distraction on arthroscopic evaluation of syndesmotic instability: A cadaveric study. AB - BACKGROUND: To assist with visualization, orthopaedic surgeons often apply ankle distraction during arthroscopic procedures. The study aimed to investigate whether ankle distraction suppresses fibular motion in cadaveric specimens with an unstable syndesmotic injury. METHODS: Fourteen fresh-frozen above knee specimens underwent arthroscopic assessment with 1) intact ligaments, 2) after sectioning of the anterior inferior tibiofibular ligament, the interosseous ligament, and the posterior inferior tibiofibular ligament, and 3) after sectioning of the deep and superficial deltoid ligament. In all scenarios, the lateral hook test, anterior-posterior hook test, and posterior-anterior hook test were applied. Each test was performed with and without ankle distraction. Coronal plane anterior and posterior tibiofibular diastasis as well as sagittal plane tibiofibular translation due to the applied load were arthroscopically measured. FINDINGS: Tibiofibular diastasis in the coronal plane, as measured at both the anterior and posterior third of the incisura, was found to be significantly less when ankle distraction was applied, as compared to arthroscopic evaluation in the absence of distraction. In contrast, measurement of sagittal plane tibiofibular translation was not affected by ankle distraction. INTERPRETATION: Since arthroscopic findings of syndesmotic instability are subtle the differential values of the syndesmotic measurements taken on and off distraction are clinically relevant. To optimally assess syndesmotic instability one should evaluate the syndesmosis without distraction or focus on fibular motion in the sagittal plane when distraction is required. PMID- 28985487 TI - Lower-extremity dynamics of walking in neuropathic diabetic patients who wear a forefoot-offloading shoe. AB - BACKGROUND: A forefoot-offloading shoes has a negative-heel rocker outsole and is used to treat diabetic plantar forefoot ulcers, but its mechanisms of action and their association with offloading and gait stability are not sufficiently clear. METHODS: Ten neuropathic diabetic patients were tested in a forefoot-offloading shoe and subsequently in a control shoe with no specific offloading construction, both worn on the right foot (control shoe on left), while walking at 1.2m/s. 3D instrumented gait analysis and simultaneous in-shoe plantar pressure measurements were used to explain the shoe's offloading efficacy and to define centre-of pressure profiles and left-to-right symmetry in ankle joint dynamics (0-1, 1:maximum symmetry), as indicators for gait stability. FINDINGS: Compared to the control shoe, peak forefoot pressures, vertical ground reaction force, plantar flexion angle, and ankle joint moment, all in terminal stance, and the proximal to-distal centre-of-pressure trajectory were significantly reduced in the forefoot-offloading shoe (P<0.01). Peak ankle joint power was 51% lower in the forefoot-offloading shoe compared to the control shoe: 1.61 (0.35) versus 3.30 (0.84) W/kg (mean (SD), P<0.001), and was significantly associated with forefoot peak pressure (R2=0.72, P<0.001). Left-to-right symmetry in the forefoot offloading shoe was 0.39 for peak ankle joint power. INTERPRETATION: By virtue to their negative-heel rocker-outsole design, forefoot-offloading shoes significantly alter a neuropathic diabetic patient's gait towards a reduced push off power that explains the shoe's offloading efficacy. However, gait symmetry and stability are compromised, and may be factors in the low perceived walking discomfort and limited use of these shoes in clinical practice. Shoe modifications (e.g. less negative heel, a more cushioning insole) may resolve this trade-off between efficacy and usability. PMID- 28985488 TI - Plantar pressure differences between cases with symptoms of clinically diagnosed chronic exertional compartment syndrome and asymptomatic controls. AB - BACKGROUND: Anterior chronic exertional compartment syndrome of the leg has been hypothesised to develop due to excessive muscle activity and foot pronation. Plantar pressure variables related to lower limb muscle activity and foot type may therefore provide insight into this condition. METHODS: 70 male cases and 70 asymptomatic controls participated. A clinical diagnosis was established from typical symptoms, with clinical examination excluding other pathologies. Plantar pressure variables during walking, hypothesised to be related to foot type, toe extensor activity or had shown predictive validity for general exercise-related lower leg pain, were extracted. FINDINGS: Cases were shorter in height (mean difference 2.4cm), had greater body mass (mean difference 4.4kg) and had reduced ankle dorsiflexion range of motion than controls (mean difference 1.5cm). Plantar pressure variables indicative of foot-type and toe extensor activity did not differ between groups (P>0.05). The magnitude of medial forefoot loading was the strongest plantar pressure predictor of the presence of chronic exertional compartment syndrome (Odds ratio:0.87, P=0.005). There was also some evidence of greater lateral heel loading at 5% of stance time (P=0.049-0.054). INTERPRETATION: The lack of association with foottype-related and toe extensor activity-related plantar pressure variables suggest that these are not risk factors for the development of chronic exertional compartment syndrome, contrary to earlier hypotheses. The greater lateral to medial loading could theoretically represent increased Tibialis anterior muscle activity at heel strike but a subsequent loss of control as the ankle is lowered. Future studies directly investigating muscle activity and function are now required. PMID- 28985489 TI - Changes in gait characteristics of women with early and established medial knee osteoarthritis: Results from a 2-years longitudinal study. AB - BACKGROUND: Despite the large number of cross-sectional studies on gait in subjects with knee osteoarthritis, there are scarcely any longitudinal studies on gait changes in knee osteoarthritis. METHODS: Gait analysis was performed on 25 women with early and 18 with established medial knee osteoarthritis, as well as a group of 23 healthy controls. Subjects were asked to walk at their comfortable speed. Kinematic and kinetic data were measured at baseline and after 2years follow-up. FINDINGS: Results indicated that the early osteoarthritis group, similar to established osteoarthritis group, showed significantly higher maximum knee adduction angles compared to the controls during the early stance phase of gait. None of the kinematic or kinetic measures, changed over two years in the early osteoarthritis group. In the established osteoarthritis group, at the time of entry, an increased first and second peak knee adduction moment, as well as higher mid-stance knee adduction moment and knee adduction moment impulse, were present compared to the control and the early osteoarthritis groups. Mid-stance knee adduction moment and knee adduction moment impulse, further increased over two years only in the established osteoarthritis group. For all three groups, the peak knee flexion angle during the stance phase decreased significantly over time. INTERPRETATION: Increased maximum knee adduction angle during stance phase was the only alteration in the gait pattern of subjects with early knee osteoarthritis compared to the controls. This suggests that, unlike in the later stages of the disease, gait is rather stable over two years in early osteoarthritis. PMID- 28985490 TI - Bone grafting in oblique versus prepared rectangular uncontained glenoid defects in reversed shoulder arthroplasty. A biomechanical comparison. AB - BACKGROUND: How the shape of the glenoid defect being reconstructed influences stability in reversed shoulder arthroplasty has never been evaluated. The purpose of this study was to compare the reconstruction of two different shaped defects in reversed shoulder arthroplasty. METHODS: Two groups (ten Sawbone scapulae each) of oblique- and rectangular-shaped glenoid defects were tested biomechanically. On the anterior half of the glenoid, bony defects (rectangular and oblique shaped) were prepared and reconstructed subsequently with a graft and reversed shoulder arthroplasty. As a control group, Sawbones without glenoid deficiency were used. In addition, these tests were reproduced in cadavers. FINDINGS: In Sawbones, no significant difference in initial stability was found between the two groups (p>0.05). Additionally, in the cadaver tests no significant difference was found between the groups with different defects (p>0.05). During the preparation, macroscopic loosening of the oblique bone grafts was found in three cases after the performance of the reversed shoulder arthroplasty due to the lack of medial support. The localization of the highest micromotion were measured primarily between the scapula bone and the graft compared to the measured micromotions between glenoid implant and the graft. INTERPRETATION: If the oblique-shaped bone graft was secured under the baseplate, the rectangular defect preparation did not show a significantly higher primary stability. However, the advantage of medial support in rectangular defects leads to more stability while placing the bone graft and baseplate during the surgical technique and should therefore be considered a preferable option. PMID- 28985491 TI - Tanshinone IIA ameliorated endothelial dysfunction in rats with chronic intermittent hypoxia. AB - Chronic intermittent hypoxia (CIH) during repetitive airflow cessations may cause endothelial dysfunction. Tanshinone IIA (Tan IIA) has been used to treat various circulatory disturbance-related diseases because of its pharmacological actions, including vasodilation. However, the mechanism of the effect of its vasodilation is not well established. The objective of this study was to explore the effect of Tan IIA in endothelium-dependent contracting factors and endothelin receptors in aortic endothelial dysfunction in CIH rats. Aortas of rats were retrieved for use in in vitro experiments (isometric force measurement), histological analysis, immunohistochemistry, and Western blotting. Tan IIA treatment increased the expression of endothelial nitric oxide synthase (eNOS) and formation of nitric oxide (NO), inhibited the production of endothelin-1 (ET-1), down-regulated ETA receptor expression, and up-regulated ETB receptor expression. In conclusion, Tan IIA protects endothelial function by inhibiting strain-induced ET-1 expression, decreasing ETA receptors, increasing ETB receptors, increasing the formation of NO, and up-regulating eNOS in CIH. PMID- 28985492 TI - Primary cardiac diffuse large B-cell lymphoma with concurrent high MYC and BCL2 expression in an immunocompetent Chinese elderly woman. AB - Primary cardiac lymphoma is a rare type of extranodal lymphoma that involves only heart and/or pericardium. It is usually observed in immunodeficient people. However, immunocompetent patients may also suffer from this disease. Most primary cardiac lymphomas are of B-cell lineage, and they usually present as diffuse large B-cell lymphoma (DLBCL). Diffuse large B-cell lymphoma with concurrently high MYC and BCL2 expression, which is named as double-expressor lymphoma (DEL), is a rare subtype of DLBCL. Here we report a rare case of a primary cardiac DEL in an immunocompetent 65-year old Chinese woman. Echocardiography and magnetic resonance imaging revealed a mass of 6.6 cm*5.6 cm in the right atrium. No tumor formations were observed in other organs. Histopathologic examination showed that the cardiac tumor was diffuse large B-cell lymphoma, non-germinal center B-cell type by Hans algorithm. The tumor cells showed high MYC and BCL2 protein expression by immunohistochemistry, with high proliferative index. PMID- 28985493 TI - Kaempferol alleviates ox-LDL-induced apoptosis by up-regulation of autophagy via inhibiting PI3K/Akt/mTOR pathway in human endothelial cells. AB - Oxidized low-density lipoprotein (ox-LDL) has been reported to induce apoptosis of endothelial cells (ECs) and contribute to the progression of atherosclerosis. Kaempferol has been shown to possess antiatherosclerotic effect. The aim of the present study was to evaluate the effect of kaempferol on ox-LDL-induced apoptosis of human umbilical vein endothelial cells (HUVECs) and its possible molecular basis. The results showed that kaempferol alleviated ox-LDL-induced apoptosis. Kaempferol increased the ratio of LC3-II/I and beclin-1 level in ox LDL-induced HUVECs. Moreover, the expression of p-Akt and p-mTOR was down regulated after treatment with kaempferol in ox-LDL-treated HUVECs, which is similar to the effect of PI3K inhibitor (LY294002) or mTOR inhibitor [rapamycin (RAP)]. Besides, autophagy induced by kaempferol was enhanced by LY294002 or RAP, while kaempferol-induced autophagy was attenuated with insulin treatment, the activator of PI3K/Akt/mTOR pathway. Furthermore, insulin also abated the effect of kaempferol on cell viability and apoptosis in ox-LDL-induced HUVECs. The results indicated that kaempferol alleviated ox-LDL-induced cell apoptosis by up regulation of autophagy via inhibiting PI3K/Akt/mTOR pathway in human ECs. PMID- 28985494 TI - The Contribution of Neanderthals to Phenotypic Variation in Modern Humans. AB - Assessing the genetic contribution of Neanderthals to non-disease phenotypes in modern humans has been difficult because of the absence of large cohorts for which common phenotype information is available. Using baseline phenotypes collected for 112,000 individuals by the UK Biobank, we can now elaborate on previous findings that identified associations between signatures of positive selection on Neanderthal DNA and various modern human traits but not any specific phenotypic consequences. Here, we show that Neanderthal DNA affects skin tone and hair color, height, sleeping patterns, mood, and smoking status in present-day Europeans. Interestingly, multiple Neanderthal alleles at different loci contribute to skin and hair color in present-day Europeans, and these Neanderthal alleles contribute to both lighter and darker skin tones and hair color, suggesting that Neanderthals themselves were most likely variable in these traits. PMID- 28985496 TI - DOMINO: Using Machine Learning to Predict Genes Associated with Dominant Disorders. AB - In contrast to recessive conditions with biallelic inheritance, identification of dominant (monoallelic) mutations for Mendelian disorders is more difficult, because of the abundance of benign heterozygous variants that act as massive background noise (typically, in a 400:1 excess ratio). To reduce this overflow of false positives in next-generation sequencing (NGS) screens, we developed DOMINO, a tool assessing the likelihood for a gene to harbor dominant changes. Unlike commonly-used predictors of pathogenicity, DOMINO takes into consideration features that are the properties of genes, rather than of variants. It uses a machine-learning approach to extract discriminant information from a broad array of features (N = 432), including: genomic data, intra-, and interspecies conservation, gene expression, protein-protein interactions, protein structure, etc. DOMINO's iterative architecture includes a training process on 985 genes with well-established inheritance patterns for Mendelian conditions, and repeated cross-validation that optimizes its discriminant power. When validated on 99 newly-discovered genes with pathogenic mutations, the algorithm displays an excellent final performance, with an area under the curve (AUC) of 0.92. Furthermore, unsupervised analysis by DOMINO of real sets of NGS data from individuals with intellectual disability or epilepsy correctly recognizes known genes and predicts 9 new candidates, with very high confidence. In summary, DOMINO is a robust and reliable tool that can infer dominance of candidate genes with high sensitivity and specificity, making it a useful complement to any NGS pipeline dealing with the analysis of the morbid human genome. PMID- 28985495 TI - Mendelian Randomization Analysis Identifies CpG Sites as Putative Mediators for Genetic Influences on Cardiovascular Disease Risk. AB - The extent to which genetic influences on cardiovascular disease risk are mediated by changes in DNA methylation levels has not been systematically explored. We developed an analytical framework that integrates genetic fine mapping and Mendelian randomization with epigenome-wide association studies to evaluate the causal relationships between methylation levels and 14 cardiovascular disease traits. We identified ten genetic loci known to influence proximal DNA methylation which were also associated with cardiovascular traits after multiple-testing correction. Bivariate fine mapping provided evidence that the individual variants responsible for the observed effects on cardiovascular traits at the ADCY3 and ADIPOQ loci were potentially mediated through changes in DNA methylation, although we highlight that we are unable to reliably separate causality from horizontal pleiotropy. Estimates of causal effects were replicated with results from large-scale consortia. Genetic variants and CpG sites identified in this study were enriched for histone mark peaks in relevant tissue types and gene promoter regions. Integrating our results with expression quantitative trait loci data, we provide evidence that variation at these regulatory regions is likely to also influence gene expression levels at these loci. PMID- 28985497 TI - Dominant Mutations in GRM1 Cause Spinocerebellar Ataxia Type 44. PMID- 28985498 TI - Leveraging Multi-ethnic Evidence for Risk Assessment of Quantitative Traits in Minority Populations. PMID- 28985499 TI - Measurement of backbone hydrogen-deuterium exchange in the type III secretion system needle protein PrgI by solid-state NMR. AB - In this report we present site-specific measurements of amide hydrogen-deuterium exchange rates in a protein in the solid state phase by MAS NMR. Employing perdeuteration, proton detection and a high external magnetic field we could adopt the highly efficient Relax-EXSY protocol previously developed for liquid state NMR. According to this method, we measured the contribution of hydrogen exchange on apparent 15N longitudinal relaxation rates in samples with differing D2O buffer content. Differences in the apparent T1 times allowed us to derive exchange rates for multiple residues in the type III secretion system needle protein. PMID- 28985500 TI - The Continuing SAGA of TFIID and RNA Polymerase II Transcription. AB - Using improved techniques, Baptista et al. (2017) and Warfield et al. (2017) revisit fundamental questions about SAGA and TFIID function in yeast. They conclude that each complex independently contributes to the expression of all genes transcribed by RNA polymerase II. PMID- 28985501 TI - Intragenic Enhancers Attenuate Host Gene Expression. AB - Eukaryotic gene transcription is regulated at many steps, including RNA polymerase II (Pol II) recruitment, transcription initiation, promoter-proximal Pol II pause release, and transcription termination; however, mechanisms regulating transcription during productive elongation remain poorly understood. Enhancers, which activate gene transcription, themselves undergo Pol II-mediated transcription, but our understanding of enhancer transcription and enhancer RNAs (eRNAs) remains incomplete. Here we show that transcription at intragenic enhancers interferes with and attenuates host gene transcription during productive elongation. While the extent of attenuation correlates positively with nascent eRNA expression, the act of intragenic enhancer transcription alone, but not eRNAs, explains the attenuation. Through CRISPR/Cas9-mediated deletions, we demonstrate a physiological role for intragenic enhancer-mediated transcription attenuation in cell fate determination. We propose that intragenic enhancers not only enhance transcription of one or more genes from a distance but also fine tune transcription of their host gene through transcription interference, facilitating differential utilization of the same regulatory element for disparate functions. PMID- 28985502 TI - The Revolution Continues: Newly Discovered Systems Expand the CRISPR-Cas Toolkit. AB - CRISPR-Cas systems defend prokaryotes against bacteriophages and mobile genetic elements and serve as the basis for revolutionary tools for genetic engineering. Class 2 CRISPR-Cas systems use single Cas endonucleases paired with guide RNAs to cleave complementary nucleic acid targets, enabling programmable sequence specific targeting with minimal machinery. Recent discoveries of previously unidentified CRISPR-Cas systems have uncovered a deep reservoir of potential biotechnological tools beyond the well-characterized Type II Cas9 systems. Here we review the current mechanistic understanding of newly discovered single protein Cas endonucleases. Comparison of these Cas effectors reveals substantial mechanistic diversity, underscoring the phylogenetic divergence of related CRISPR Cas systems. This diversity has enabled further expansion of CRISPR-Cas biotechnological toolkits, with wide-ranging applications from genome editing to diagnostic tools based on various Cas endonuclease activities. These advances highlight the exciting prospects for future tools based on the continually expanding set of CRISPR-Cas systems. PMID- 28985503 TI - A Peptide Encoded by a Putative lncRNA HOXB-AS3 Suppresses Colon Cancer Growth. AB - A substantial fraction of eukaryotic transcripts are considered long non-coding RNAs (lncRNAs), which regulate various hallmarks of cancer. Here, we discovered that the lncRNA HOXB-AS3 encodes a conserved 53-aa peptide. The HOXB-AS3 peptide, not lncRNA, suppresses colon cancer (CRC) growth. Mechanistically, the HOXB-AS3 peptide competitively binds to the ariginine residues in RGG motif of hnRNP A1 and antagonizes the hnRNP A1-mediated regulation of pyruvate kinase M (PKM) splicing by blocking the binding of the ariginine residues in RGG motif of hnRNP A1 to the sequences flanking PKM exon 9, ensuring the formation of lower PKM2 and suppressing glucose metabolism reprogramming. CRC patients with low levels of HOXB-AS3 peptide have poorer prognoses. Our study indicates that the loss of HOXB AS3 peptide is a critical oncogenic event in CRC metabolic reprogramming. Our findings uncover a complex regulatory mechanism of cancer metabolism reprogramming orchestrated by a peptide encoded by an lncRNA. PMID- 28985504 TI - CLOCK Acetylates ASS1 to Drive Circadian Rhythm of Ureagenesis. AB - In addition to responding to environmental entrainment with diurnal variation, metabolism is also tightly controlled by cell-autonomous circadian clock. Extensive studies have revealed key roles of transcription in circadian control. Post-transcriptional regulation for the rhythmic gating of metabolic enzymes remains elusive. Here, we show that arginine biosynthesis and subsequent ureagenesis are collectively regulated by CLOCK (circadian locomotor output cycles kaput) in circadian rhythms. Facilitated by BMAL1 (brain and muscle Arnt like protein), CLOCK directly acetylates K165 and K176 of argininosuccinate synthase (ASS1) to inactivate ASS1, which catalyzes the rate-limiting step of arginine biosynthesis. ASS1 acetylation by CLOCK exhibits circadian oscillation in human cells and mouse liver, possibly caused by rhythmic interaction between CLOCK and ASS1, leading to the circadian regulation of ASS1 and ureagenesis. Furthermore, we also identified NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9 (NDUFA9) and inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) as acetylation substrates of CLOCK. Taken together, CLOCK modulates metabolic rhythmicity by acting as a rhythmic acetyl-transferase for metabolic enzymes. PMID- 28985505 TI - Combined CRISPRi/a-Based Chemical Genetic Screens Reveal that Rigosertib Is a Microtubule-Destabilizing Agent. AB - Chemical libraries paired with phenotypic screens can now readily identify compounds with therapeutic potential. A central limitation to exploiting these compounds, however, has been in identifying their relevant cellular targets. Here, we present a two-tiered CRISPR-mediated chemical-genetic strategy for target identification: combined genome-wide knockdown and overexpression screening as well as focused, comparative chemical-genetic profiling. Application of these strategies to rigosertib, a drug in phase 3 clinical trials for high risk myelodysplastic syndrome whose molecular target had remained controversial, pointed singularly to microtubules as rigosertib's target. We showed that rigosertib indeed directly binds to and destabilizes microtubules using cell biological, in vitro, and structural approaches. Finally, expression of tubulin with a structure-guided mutation in the rigosertib-binding pocket conferred resistance to rigosertib, establishing that rigosertib kills cancer cells by destabilizing microtubules. These results demonstrate the power of our chemical genetic screening strategies for pinpointing the physiologically relevant targets of chemical agents. PMID- 28985506 TI - NRF2 Is a Major Target of ARF in p53-Independent Tumor Suppression. AB - Although ARF can suppress tumor growth by activating p53 function, the mechanisms by which it suppresses tumor growth independently of p53 are not well understood. Here, we identified ARF as a key regulator of nuclear factor E2-related factor 2 (NRF2) through complex purification. ARF inhibits the ability of NRF2 to transcriptionally activate its target genes, including SLC7A11, a component of the cystine/glutamate antiporter that regulates reactive oxygen species (ROS) induced ferroptosis. As a consequence, ARF expression sensitizes cells to ferroptosis in a p53-independent manner while ARF depletion induces NRF2 activation and promotes cancer cell survival in response to oxidative stress. Moreover, the ability of ARF to induce p53-independent tumor growth suppression in mouse xenograft models is significantly abrogated upon NRF2 overexpression. These results demonstrate that NRF2 is a major target of p53-independent tumor suppression by ARF and also suggest that the ARF-NRF2 interaction acts as a new checkpoint for oxidative stress responses. PMID- 28985507 TI - Randomized CRISPR-Cas Transcriptional Perturbation Screening Reveals Protective Genes against Alpha-Synuclein Toxicity. AB - The genome-wide perturbation of transcriptional networks with CRISPR-Cas technology has primarily involved systematic and targeted gene modulation. Here, we developed PRISM (Perturbing Regulatory Interactions by Synthetic Modulators), a screening platform that uses randomized CRISPR-Cas transcription factors (crisprTFs) to globally perturb transcriptional networks. By applying PRISM to a yeast model of Parkinson's disease (PD), we identified guide RNAs (gRNAs) that modulate transcriptional networks and protect cells from alpha-synuclein (alphaSyn) toxicity. One gRNA identified in this screen outperformed the most protective suppressors of alphaSyn toxicity reported previously, highlighting PRISM's ability to identify modulators of important phenotypes. Gene expression profiling revealed genes differentially modulated by this strong protective gRNA that rescued yeast from alphaSyn toxicity when overexpressed. Human homologs of top-ranked hits protected against alphaSyn-induced cell death in a human neuronal PD model. Thus, high-throughput and unbiased perturbation of transcriptional networks via randomized crisprTFs can reveal complex biological phenotypes and effective disease modulators. PMID- 28985509 TI - Untangling P-Bodies: Dissecting the Complex Web of Interactions that Enable Tiered Control of Gene Expression. AB - In this issue of Molecular Cell, Hubstenberger et al. (2017) define the molecular composition of P-bodies isolated from human epithelial cells to propose that these foci act as mRNA storage depots rather than mRNA decay facilities. PMID- 28985511 TI - Epigenetic Control of NRF2-Directed Cellular Antioxidant Status in Dictating Life Death Decisions. AB - In this issue of Molecular Cell, Chen et al. (2017) demonstrate that the tumor suppressor protein ARF sensitizes cancer cells to programmed death through a surprising mechanism: ARF physically interacts with and antagonizes activation by acetylation of the master redox regulator NRF2, providing an unusual mode of posttranslational NRF2 regulation. PMID- 28985508 TI - Methods and Applications of CRISPR-Mediated Base Editing in Eukaryotic Genomes. AB - The past several years have seen an explosion in development of applications for the CRISPR-Cas9 system, from efficient genome editing, to high-throughput screening, to recruitment of a range of DNA and chromatin-modifying enzymes. While homology-directed repair (HDR) coupled with Cas9 nuclease cleavage has been used with great success to repair and re-write genomes, recently developed base editing systems present a useful orthogonal strategy to engineer nucleotide substitutions. Base editing relies on recruitment of cytidine deaminases to introduce changes (rather than double-stranded breaks and donor templates) and offers potential improvements in efficiency while limiting damage and simplifying the delivery of editing machinery. At the same time, these systems enable novel mutagenesis strategies to introduce sequence diversity for engineering and discovery. Here, we review the different base-editing platforms, including their deaminase recruitment strategies and editing outcomes, and compare them to other CRISPR genome-editing technologies. Additionally, we discuss how these systems have been applied in therapeutic, engineering, and research settings. Lastly, we explore future directions of this emerging technology. PMID- 28985512 TI - The Anti-CRISPR Story: A Battle for Survival. AB - The last decade has seen the fields of molecular biology and genetics transformed by the development of CRISPR-based gene editing technologies. These technologies were derived from bacterial defense systems that protect against viral invasion. Elegant studies focused on the evolutionary battle between CRISPR-encoding bacteria and the viruses that infect and kill them revealed the next step in this arms race, the anti-CRISPR proteins. Investigation of these proteins has provided important new insight into how CRISPR-Cas systems work and how bacterial genomes evolve. They have also led to the development of important biotechnological tools that can be used for genetic engineering, including off switches for CRISPR-Cas9 genome editing in human cells. PMID- 28985510 TI - High-Throughput Approaches to Pinpoint Function within the Noncoding Genome. AB - The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas nuclease system is a powerful tool for genome editing, and its simple programmability has enabled high-throughput genetic and epigenetic studies. These high-throughput approaches offer investigators a toolkit for functional interrogation of not only protein-coding genes but also noncoding DNA. Historically, noncoding DNA has lacked the detailed characterization that has been applied to protein-coding genes in large part because there has not been a robust set of methodologies for perturbing these regions. Although the majority of high-throughput CRISPR screens have focused on the coding genome to date, an increasing number of CRISPR screens targeting noncoding genomic regions continue to emerge. Here, we review high-throughput CRISPR-based approaches to uncover and understand functional elements within the noncoding genome and discuss practical aspects of noncoding library design and screen analysis. PMID- 28985513 TI - Increasing air humidity influences hydraulic efficiency but not functional vulnerability of xylem in hybrid aspen. AB - Climate models predict greater increases in the frequency than in the amount of precipitation and a consequent rise in atmospheric humidity at high latitudes by the end of the century. We investigated the responses of hydraulic and relevant anatomical traits of xylem to elevated relative humidity of air on a 1-yr-old coppice of hybrid aspen (Populus*wettsteinii) growing in the experimental stand at the Free Air Humidity Manipulation site in Eastern Estonia. The hydraulic conductivity of stems was measured with a high pressure flow meter; artificial cavitation in the stem segments was induced by the air injection method. Specific conductivity of xylem decreased from 4.42 in the control to 3.94kgm-1s-1MPa-1 in the humidification treatment, while the trend was well correlated with increasing wood density. Humidified trees exhibited smaller leaf area at the same xylem cross-sectional area, resulting in 34% higher average Huber values compared to the control. Control and humidity-treated trees differed by neither native embolism level nor susceptibility to dehydration-induced cavitation. Increasing atmospheric humidity reduces the hydraulic efficiency of hybrid aspen trees expressed on a xylem area basis and causes substantial changes in resource allocation between photosynthetic and water transport tissues. This climate trend does not influence stem vulnerability to cavitation. PMID- 28985514 TI - Visceral adipose tissue macrophage-targeted TACE silencing to treat obesity induced type 2 diabetes. AB - Obesity is an increasingly prevalent global health problem. Due to its close relations with metabolic diseases and cancer, new therapeutic approaches for treating obesity and obesity-induced metabolic diseases are required. Visceral white adipose tissue (WAT) has been closely associated with obesity-induced inflammation and adipose tissue macrophages (ATMs) are responsible for obesity induced inflammation by releasing inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6. TNF-alpha converting enzyme (TACE) is a transmembrane enzyme that induces the enzymatic cleavage and release of inflammatory cytokines. In this study, we developed a nonviral gene delivery system consisting of an oligopeptide (ATS-9R) that can selectively target visceral ATMs. In here we shows visceral adipose tissue-dominant inflammatory gene over-expressions in obese mouse and our strategy enabled the preferential delivery of therapeutic genes to visceral ATMs and successfully achieved ATM targeted gene silencing. Finally, ATS-9R-mediated TACE gene silencing in visceral ATMs alleviated visceral fat inflammation and improved type 2 diabetes by reducing whole body inflammation. PMID- 28985515 TI - Geographical differences in risk of advanced breast cancer: Limited evidence for reductions over time, Queensland, Australia 1997-2014. AB - BACKGROUND: Reducing geographical inequalities in breast cancer stage remains a key focus of public health policy. We explored whether patterns of advanced breast cancer by residential accessibility and disadvantage in Queensland, Australia, have changed over time. METHODS: Population-based cancer registry study of 38,706 women aged at least 30 years diagnosed with a first primary invasive breast cancer of known stage between 1997 and 2014. Multilevel logistic regression was used to examine temporal changes in associations of area-level factors with odds of advanced disease after adjustment for individual-level factors. RESULTS: Overall 19,401 (50%) women had advanced breast cancer. Women from the most disadvantaged areas had higher adjusted odds (OR = 1.23 [95%CI 1.13, 1.32]) of advanced disease than those from least disadvantaged areas, with no evidence this association had changed over time (interaction p = 0.197). Living in less accessible areas independently increased the adjusted odds (OR = 1.18 [1.09, 1.28]) of advanced disease, with some evidence that the geographical inequality had reduced over time (p = 0.045). Sensitivity analyses for un-staged cases showed that the original associations remained, regardless of assumptions made about the true stage distribution. CONCLUSIONS: Both geographical and residential socioeconomic inequalities in advanced stage diagnoses persist, potentially reflecting barriers in accessing diagnostic services. Given the role of screening mammography in early detection of breast cancer, the lack of population-based data on private screening limits our ability to determine overall participation rates by residential characteristics. Without such data, the efficacy of strategies to reduce inequalities in breast cancer stage will remain compromised. PMID- 28985516 TI - Assessment of spatial variation in breast cancer-specific mortality using Louisiana SEER data. AB - BACKGROUND: Previous studies suggest spatial differences in mortality for many types of cancer, including breast cancer. Identifying explanations for these spatial differences results in a better understanding of what leads to longer survival time. METHODS: We used a Bayesian accelerated failure time model with spatial frailty terms to investigate potential spatial differences in breast cancer mortality following breast cancer diagnosis using 2000-2013 Louisiana SEER data. RESULTS: There are meaningful spatial differences in breast cancer mortality across the parishes of Louisiana, even after adjusting for known demographic and clinical risk factors. For example, the average survival time of a woman diagnosed in Orleans parish was 1.51 times longer than that of a woman diagnosed in Terrebonne parish. Additionally, there is evidence to suggest shorter survival times in lower income parishes along the Red and Mississippi Rivers, as well as parishes with lower socioeconomic status, less access to care and fresh food, worse quality of care, and more workers in certain industries. CONCLUSION: The addition of spatial frailties to account for an individual's geographic location is useful when analyzing breast cancer mortality data. Our findings suggest that survival following breast cancer diagnosis could potentially be improved if socioeconomic status differences were addressed, healthcare improved in quality and became more accessible, and certain industrial situations were improved for individuals diagnosed in parishes identified as having shorter average survival times. PMID- 28985518 TI - The LUNGe to Model Alveolar Lung Diseases in a Dish. AB - Obtaining alveolar epithelial type 2 cells (AEC2s) from human pluripotent stem cells (hPSCs) offers great scientific and clinical promise. In this issue of Cell Stem Cell, Jacob et al. (2017) report a method for the directed differentiation of hPSCs into mature AEC2s and demonstrate its application in modeling alveolar lung diseases. PMID- 28985517 TI - Effect of common antivertiginous agents on the high velocity vestibulo-ocular reflex. AB - OBJECTIVE: It has long been suggested that antivertiginous medications exert their symptomatic effect through inhibition of the vestibulo-ocular reflex (VOR). We tested this hypothesis by directly measuring the VOR after administration of three agents from different substance classes: an antihistamine, a benzodiazepine and a calcium channel antagonist. METHODS: The gain and the variability of the high velocity VOR was assessed using video head impulses (vHIT) under the following conditions: baseline, after dimenhydrinate, after diazepam and after cinnarizine. RESULTS: We found that all three medications did not change any VOR gain or variability parameter: At 60ms, the gain was 0.95 at baseline, 0.99 under dimenhydrinate, 0.99 under diazepam and 0.96 under cinnarizine. The gain variability across repetitive head impulses remained also uninfluenced. CONCLUSIONS: The human high frequency VOR remains robust to pharmacological perturbations at common clinical doses and the assumption that symptomatic vertigo relief is achieved merely through impairment of the VOR requires re examination. SIGNIFICANCE: Alternative mechanisms of pharmacological action might be operant, such as the modulation of vestibulo-cortical pathways, a differential effect on the low frequency VOR and an altered sensitivity to drugs in acute unilateral vestibulopathy. PMID- 28985519 TI - E Pluribus Unum ("Out of Many, One"): CRISPR Modeling of Myeloid Expansion. AB - In this issue of Cell Stem Cell, Tothova et al. (2017) demonstrate a promising way to model the complex genetics of clonal hematopoiesis and myeloid disorders using CRISPR-Cas9 genome editing in human hematopoietic stem and progenitor cells. Their approach opens the door to genotype-specific pharmacologic testing. PMID- 28985520 TI - Gut with the Program: Direct Reprogramming toward Intestinal Epithelium Realized. AB - Intestinal organoids offer great promise for modeling intestinal diseases; however, harvesting intestinal tissue is invasive and directed hPSC differentiation protocols are laborious and costly. In this issue of Cell Stem Cell, Miura and Suzuki (2017) describe the direct conversion of somatic cells from both mice and humans into robust intestinal epithelial tissue. PMID- 28985521 TI - Policing Tumorigenesis within the Skin: Good Outs Bad. AB - Recently published in Nature, Brown et al. (2017) shed new light on how the skin handles the activation of oncogenic pathways in the stem cell compartment and how wild-type cells limit the proliferation of mutant cells to maintain proper tissue homeostasis. PMID- 28985522 TI - Mononuclear Diploidy at the Heart of Cardiomyocyte Proliferation. AB - Reporting in Nature Genetics, Patterson et al. (2017) show that adult mammalian hearts possess an innate capacity to regenerate, which depends on a small population of mononuclear diploid cardiomyocytes. These cells undergo karyokinesis and cytokinesis, raising the possibility that endogenous cardiac muscle cells can be stimulated to proliferate for myocardial repair. PMID- 28985523 TI - Human Embryo Editing: Opportunities and Importance of Transnational Cooperation. AB - A recent National Academies report articulates a path forward for research, ethics, and governance of clinical applications involving genome editing. In light of recent human embryo editing developments, scientists and stakeholders from all nations should cooperate to take advantage of this historic opportunity for medicine and also basic human biology. PMID- 28985524 TI - Human Genome Editing in the Clinic: New Challenges in Regulatory Benefit-Risk Assessment. AB - As genome editing rapidly progresses toward the realization of its clinical promise, assessing the suitability of current tools and processes used for its benefit-risk assessment is critical. Although current regulations may initially provide an adequate regulatory framework, improvements are recommended to overcome several existing technology-based safety and efficacy issues. PMID- 28985526 TI - Distinct Cell-Cycle Control in Two Different States of Mouse Pluripotency. AB - Mouse embryonic stem cells (ESCs) cultured in serum are characterized by hyper phosphorylated RB protein, lack of G1 control, and rapid progression through the cell cycle. Here, we show that ESCs grown in the presence of two small-molecule inhibitors (2i ESCs) have a longer G1-phase with hypo-phosphorylated RB, implying that they have a functional G1 checkpoint. Deletion of RB, P107, and P130 in 2i ESCs results in a G1-phase similar to that of serum ESCs. Inhibition of the ERK signaling pathway in serum ESCs results in the appearance of hypo-phosphorylated RB and the reinstatement of a G1 checkpoint. In addition, induction of a dormant state by the inhibition of MYC, resembling diapause, requires the presence of the RB family proteins. Collectively, our data show that RB-dependent G1 restriction point signaling is active in mouse ESCs grown in 2i but abrogated in serum by ERK dependent phosphorylation. PMID- 28985527 TI - Evolutionarily Distinctive Transcriptional and Signaling Programs Drive Human Germ Cell Lineage Specification from Pluripotent Stem Cells. AB - Germline specification underlies human reproduction and evolution, but it has proven difficult to study in humans since it occurs shortly after blastocyst implantation. This process can be modeled with human induced pluripotent stem cells (hiPSCs) by differentiating them into primordial germ cell-like cells (hPGCLCs) through an incipient mesoderm-like cell (iMeLC) state. Here, we elucidate the key transcription factors and their interactions with important signaling pathways in driving hPGCLC differentiation from iPSCs. Germline competence of iMeLCs is dictated by the duration and dosage of WNT signaling, which induces expression of EOMES to activate SOX17, a key driver of hPGCLC specification. Upon hPGCLC induction, BMP signaling activates TFAP2C in a SOX17 independent manner. SOX17 and TFAP2C then cooperatively instate an hPGCLC transcriptional program, including BLIMP1 expression. This specification program diverges from its mouse counterpart regarding key transcription factors and their hierarchies, and it provides a foundation for further study of human germ cell development. PMID- 28985525 TI - CRISPR/Cas9-Based Engineering of the Epigenome. AB - Determining causal relationships between distinct chromatin features and gene expression, and ultimately cell behavior, remains a major challenge. Recent developments in targetable epigenome-editing tools enable us to assign direct transcriptional and functional consequences to locus-specific chromatin modifications. This Protocol Review discusses the unprecedented opportunity that CRISPR/Cas9 technology offers for investigating and manipulating the epigenome to facilitate further understanding of stem cell biology and engineering of stem cells for therapeutic applications. We also provide technical considerations for standardization and further improvement of the CRISPR/Cas9-based tools to engineer the epigenome. PMID- 28985530 TI - A 5-HT1Areceptor promoter polymorphism influences fronto-limbic functional connectivity and depression severity in bipolar disorder. PMID- 28985528 TI - Chromatin and Single-Cell RNA-Seq Profiling Reveal Dynamic Signaling and Metabolic Transitions during Human Spermatogonial Stem Cell Development. AB - Human adult spermatogonial stem cells (hSSCs) must balance self-renewal and differentiation. To understand how this is achieved, we profiled DNA methylation and open chromatin (ATAC-seq) in SSEA4+ hSSCs, analyzed bulk and single-cell RNA transcriptomes (RNA-seq) in SSEA4+ hSSCs and differentiating c-KIT+ spermatogonia, and performed validation studies via immunofluorescence. First, DNA hypomethylation at embryonic developmental genes supports their epigenetic "poising" in hSSCs for future/embryonic expression, while core pluripotency genes (OCT4 and NANOG) were transcriptionally and epigenetically repressed. Interestingly, open chromatin in hSSCs was strikingly enriched in binding sites for pioneer factors (NFYA/B, DMRT1, and hormone receptors). Remarkably, single cell RNA-seq clustering analysis identified four cellular/developmental states during hSSC differentiation, involving major transitions in cell-cycle and transcriptional regulators, splicing and signaling factors, and glucose/mitochondria regulators. Overall, our results outline the dynamic chromatin/transcription landscape operating in hSSCs and identify crucial molecular pathways that accompany the transition from quiescence to proliferation and differentiation. PMID- 28985529 TI - Multiplex CRISPR/Cas9-Based Genome Editing in Human Hematopoietic Stem Cells Models Clonal Hematopoiesis and Myeloid Neoplasia. AB - Hematologic malignancies are driven by combinations of genetic lesions that have been difficult to model in human cells. We used CRISPR/Cas9 genome engineering of primary adult and umbilical cord blood CD34+ human hematopoietic stem and progenitor cells (HSPCs), the cells of origin for myeloid pre-malignant and malignant diseases, followed by transplantation into immunodeficient mice to generate genetic models of clonal hematopoiesis and neoplasia. Human hematopoietic cells bearing mutations in combinations of genes, including cohesin complex genes, observed in myeloid malignancies generated immunophenotypically defined neoplastic clones capable of long-term, multi-lineage reconstitution and serial transplantation. Employing these models to investigate therapeutic efficacy, we found that TET2 and cohesin-mutated hematopoietic cells were sensitive to azacitidine treatment. These findings demonstrate the potential for generating genetically defined models of human myeloid diseases, and they are suitable for examining the biological consequences of somatic mutations and the testing of therapeutic agents. PMID- 28985531 TI - Spatial structure normalises working memory performance in Parkinson's disease. AB - Cognitive deficits are a frequent symptom of Parkinson's disease (PD), particularly in the domain of spatial working memory (WM). Despite numerous demonstrations of aberrant WM in patients, there is a lack of understanding about how, if at all, their WM is fundamentally altered. Most notably, it is unclear whether span - the yardstick upon which most WM models are built - is compromised by the disease. Moreover, it is also unknown whether WM deficits occur in all patients or only exist in a sub-group who are executively impaired. We assessed the factors that influenced spatial span in medicated patients by varying the complexity of to-be-remembered items. Principally, we manipulated the ease with which items could enter - or be blocked from - WM by varying the level of structure in memoranda. Despite having similar levels of executive performance to controls, PD patients were only impaired when remembering information that lacked spatial, easy-to-chunk, structure. Patients' executive function, however, did not influence this effect. The ease with which patients could control WM was further examined by presenting irrelevant information during encoding, varying the level of structure in irrelevant information and manipulating the amount of switching between relevant and irrelevant information. Disease did not significantly alter the effect of these manipulations. Rather, patients' executive performance constrained the detrimental effect of irrelevant information on WM. Thus, PD patients' spatial span is predominantly determined by level of structure in to-be remembered information, whereas their level of executive function may mitigate against the detrimental effect of irrelevant information. PMID- 28985532 TI - The role of premotor and parietal cortex during monitoring of involuntary movement: A combined TMS and tDCS study. AB - Converging evidence on voluntary actions underlays the existence of a motor monitoring system able to compare the predicted and the actual consequences of our movements. In this context, both the premotor cortex (PMC) and the posterior parietal cortex (PPC) play a role in action monitoring and awareness. The present study explores the role of PMC and PPC in monitoring involuntary muscle contractions induced by transcranial magnetic stimulation (TMS) over the hand motor area. To this aim, the effects of transcranial direct current stimulation (tDCS) over PMC and PPC were examined. Thirty-six healthy subjects were asked to perform a motor monitoring task (i.e., to verbally report hand twitches induced by TMS) after 10 min of tDCS. Through three experiments, the effects of cathodal, anodal and sham tDCS over the left and the right hemispheres were compared. Our results show that cathodal tDCS over the right PMC does not affect the monitoring of involuntary movements. By contrast, tDCS over both the right and the left PPC affects motor monitoring, depending on the current polarity: while cathodal tDCS increases the feeling of phantom-like movements (which actually did not occur), anodal tDCS impairs the ability to detect involuntary hand twitches (which actually took place). These findings show that the PMC is not involved in motor monitoring of involuntary movements; rather, the PPC, where multisensory stimuli converge and are processed, seems to play a crucial role. PMID- 28985533 TI - Determination of triazine herbicides and their metabolites in multiple medicinal parts of traditional Chinese medicines using streamlined pretreatment and UFLC ESI-MS/MS. AB - A rapid, sensitive, and reliable ultra-fast liquid chromatography combined with electrospray ionization tandem mass spectrometry (UFLC-ESI-MS/MS) method was established and applied to simultaneous determination of 31 triazine herbicides and their metabolites in multiple medicinal parts of traditional Chinese medicines (TCMs). A streamlined pretreatment approach using one-step extraction and dilution was proposed, which provided high-throughput processing, excellent recovery, and negligible interference. Afterwards, multiple-reaction monitoring (MRM) and information-dependent acquisition (IDA) triggered enhanced product ion spectra (EPI) was adopted to identify and quantify the targets in a single analysis. The optimized method was then validated according to the guidelines of the European Commission for the following parameters: Matrix effects, specificity, accuracy, precision, linearity, range, and stability. The LOD and LOQ for the 31 triazine herbicides were 0.1-10 MUg kg-1 and 0.5-25 MUg kg-1, respectively. Recoveries at three concentration levels were within 67.9-120.3% with an associated precision RSD <20%. Using the proposed approach, trazines herbicides were determined from 44 commercially available TCMs. The detection rate of triazine herbicides residues was 15.9% of the total samples. Among them, atrazine, simeton, and simetryn were found in the radix, herba, and seed TCMs with values far below the referenced maximum residue limits (MRLs), but no residues were detected in either the flos or fructus. Taken together, this method has the potential to provide a means for triazines screening in extensive matrices, thereby laying the foundation for pesticide registration on TCMs. Moreover, it has the potential to guide further triazine residue control in TCMs. PMID- 28985534 TI - Organophosphate ester flame retardants in Nepalese soil: Spatial distribution, source apportionment and air-soil exchange assessment. AB - Despite soil being the major terrestrial environmental reservoir and one of the significant sinks for many hydrophobic organic compounds including organophosphate ester flame retardants (OPFRs), limited information is available about concentration and fate of OPFRs contamination in urban soil in general and especially in case of Nepal. This study investigates the environmental concentration, spatial distribution and source apportionment of eight OPFRs in surface soil (n = 28) from four major cities of Nepal with special interest on air-soil exchange. Overall, significantly high concentrations of ?8OPFR were measured in soil ranging from 25-27,900 ng/g dw (median 248 ng/g dw). In terms of compositional pattern, tris(methyl phenyl) phosphate (TMPP) was the most abundant phosphorus chemical in soil, followed by tris(2-chloroisopropyl) phosphate (TCIPP), and accounted for 35-49% and 8-25% of ?8OPFRs, respectively. The high level of these OPFRs was attributed to local sources as opposed to transboundary influence from remote areas. A Spearman's rank correlation analysis exhibited weak correlation of ?8OPFRs with TOC (Rho = 0.117, p < 0.05) and BC (Rho = 0.007, p < 0.05), suggesting little or no influence of TOC and BC on the concentration of ?8OPFRs. The fugacity fraction (ff) results indicated a strong influence of soil contamination on atmospheric level of OPFRs via volatilization. PMID- 28985535 TI - Evaluation of polyurethane foam passive air sampler (PUF) as a tool for occupational PAH measurements. AB - Routine monitoring of workplace exposure to polycyclic aromatic hydrocarbons (PAHs) is performed mainly via active sampling. However, active samplers have several drawbacks and, in some cases, may even be unusable. Polyurethane foam (PUF) as personal passive air samplers constitute good alternatives for PAH monitoring in occupational air (8 h). However, PUFs must be further tested to reliably yield detectable levels of PAHs in short exposure times (1-3 h) and under extreme occupational conditions. Therefore, we compared the personal exposure monitoring performance of a passive PUF sampler with that of an active air sampler and determined the corresponding uptake rates (Rs). These rates were then used to estimate the occupational exposure of firefighters and police forensic specialists to 32 PAHs. The work environments studied were heavily contaminated by PAHs with (for example) benzo(a)pyrene ranging from 0.2 to 56 ng m-3, as measured via active sampling. We show that, even after short exposure times, PUF can reliably accumulate both gaseous and particle-bound PAHs. The Rs values are almost independent of variables such as the concentration and the wind speed. Therefore, by using the Rs-values (2.0-20 m3 day-1), the air concentrations can be estimated within a factor of two for gaseous PAHs and a factor of 10 for particulate PAHs. With very short sampling times (1 h), our method can serve as a (i) simple and user-friendly semi-quantitative screening tool for estimating and tracking point sources of PAH in micro-environments and (ii) complement to the traditional active pumping methods. PMID- 28985536 TI - Perfluorooctane sulfonate impairs rat Leydig cell development during puberty. AB - Perfluorooctane sulfonate (PFOS) possibly delays male sexual development. However, its effects on pubertal Leydig cell development are unclear. The objective of the present study was to investigate the effects of in vivo PFOS exposure on rat Leydig cell development during puberty. Immature male Sprague Dawley rats were gavaged 5 or 10 mg/kg PFOS on postnatal day 35 for 21 days. Compared to the control (0 mg/kg), PFOS lowered serum testosterone levels without altering luteinizing hormone and follicle-stimulating hormone levels on postnatal day 56. PFOS in vivo downregulated mRNA or protein levels of Leydig cells (Lhcgr, Cyp11a1, and Cyp17a1). PFOS in vitro inhibited androgen secretion in immature Leydig cells at >= 50 nM, most possibly via downregulating Hsd17b3 mRNA level. At >= 500 nM, PFOS downregulated Lhcgr, inhibited BCL-2 and increased BAX levels to cause Leydig cell apoptosis. In conclusion, PFOS at a lower dose directly inhibited pubertal development of Leydig cells. PMID- 28985537 TI - Removal of natural organic matter in drinking water treatment by coagulation: A comprehensive review. AB - Natural organic matter (NOM) is a complex matrix of organic substances produced in (or channeled to) aquatic ecosystems via various biological, geological and hydrological cycles. Such variability is posing a serious challenge to most water treatment technologies, especially the ones designed to treat drinking water supplies. Lately, in addition to the fluctuating composition of NOM, a substantial increase of its concentration in fresh waters, and also municipal wastewater effluents, has been reported worldwide, which justifies the urgent need to develop highly efficient and versatile water treatment processes. Coagulation is among the most applied processes for water and wastewater treatment. The application of coagulation to remove NOM from drinking water supplies has received a great deal of attention from researchers around the world because it was efficient and helped avoiding the formation of disinfection by products (DBPs). Nonetheless, with the increased fluctuation of NOM in water (concentration and composition), the efficiency of conventional coagulation was substantially reduced, hence the need to develop enhanced coagulation processes by optimizing the operating conditions (mainly the amount coagulants and pH), developing more efficient inorganic or organic coagulants, as well as coupling coagulation with other water treatment technologies. In the present review, recent research studies dealing with the application of coagulation for NOM removal from drinking water supplies are presented and compared. In addition, integration schemes combining coagulation and other water treatment processes are presented, including membrane filtration, oxidation, adsorption and others processes. PMID- 28985538 TI - Thermodynamic parameters for the protonation and the interaction of arsenate with Mg2+, Ca2+ and Sr2+: Application to natural waters. AB - Thermodynamic parameters for the protonation of AsO43- and for the interaction with Mg2+, Ca2+ and Sr2+ were reported, comprehensive also of their dependence on ionic strength, considering the 0.1 <= I <= 1 M range and using NaCl as background salt. The same speciation models were obtained for Mg2+, Ca2+ and Sr2+ systems, with the formation of three different species: ML, MLH and MLH2 (L = AsO43-). Mono- and di-protonated species were very weak, with formation constant values (log K) ranging from 1.45 to 3.23. In order to have a complete picture of thermodynamic properties of the systems under study and to fill the shortage of thermodynamic data on arsenate complex systems, the ligand protonation and metal complex enthalpies were also determined by calorimetric titrations, at t = 25 degrees C and in NaCl at I = 0.7 M (for H+-AsO43- species also at I = 0.1 M). On the light of the proposed speciation models, examples of As(V) distribution in some natural waters are reported. PMID- 28985539 TI - The use of toxicokinetics and exposure studies to show that carprofen in cattle tissue could lead to secondary toxicity and death in wild vultures. AB - Veterinary medicines can be extremely damaging to the environment, as seen with the catastrophic declines in Gyps vulture in South Asia due to their secondary exposure to diclofenac in their primary food source. Not surprisingly, concern has been raised over other similar drugs. In this study, we evaluate the toxicity of carprofen to the Gyps vulture clade through plasma pharmacokinetics evaluations in Bos taurus cattle (their food source) and Gyps africanus (a validated model species); tissue residues in cattle; and the effect of carprofen as a secondary toxicant as both tissue-bound residue or pure drug at levels expected in cattle tissues. Carprofen residues were highest in cattle kidney (7.72 +/- 2.38 mg/kg) and injection site muscle (289.05 +/- 98.96 mg/kg of dimension of 5 * 5 * 5 cm). Vultures exposed to carprofen as residues in the kidney tissue or pure drug equivalents showed no toxic signs. When exposed to average injection site concentrations (64 mg/kg) one of two birds died with evidence of severe renal and liver damage. Toxicokinetic analysis revealed a prolonged drug half-life of 37.75 h in the dead bird as opposed to 13.99 +/- 5.61 h from healthy birds dosed intravenously at 5 mg/kg. While carprofen may generally be harmless to Gyps vultures, its high levels at the injection site in treated cattle can result in lethal exposure in foraging vultures, due to relative small area of tissue it is found therein. We thus suggest that carprofen not be used in domesticated ungulates in areas where carcasses are accessible or provided to vultures at supplementary feeding sites. PMID- 28985540 TI - Influence of lead on stabilization/solidification by ordinary Portland cement and magnesium phosphate cement. AB - Inorganic binder-based stabilization/solidification (S/S) of Pb-contaminated soil is a commonly used remediation approach. This paper investigates the influences of soluble Pb species on the hydration process of two types of inorganic binders: ordinary Portland cement (OPC) and magnesium potassium phosphate cement (MKPC). The environmental leachability, compressive strength, and setting time of the cement products are assessed as the primary performance indicators. The mechanisms of Pb involved in the hydration process are analyzed through X-ray diffraction (XRD), hydration heat evolution, and thermogravimetric analyses. Results show that the presence of Pb imposes adverse impact on the compressive strength (decreased by 30.4%) and the final setting time (prolonged by 334.7%) of OPC, but it exerts much less influence on those of MKPC. The reduced strength and delayed setting are attributed to the retarded hydration reaction rate of OPC during the induction period. These results suggest that the OPC-based S/S of soluble Pb mainly depends on physical encapsulation by calcium-silicate-hydrate (CSH) gels. In contrast, in case of MKPC-based S/S process, chemical stabilization with residual phosphate (pyromorphite and lead phosphate precipitation) and physical fixation of cementitious struvite-K are the major mechanisms. Therefore, MKPC is a more efficient and chemically stable inorganic binder for the Pb S/S process. PMID- 28985541 TI - Chromium (VI) removal from aqueous solutions through powdered activated carbon countercurrent two-stage adsorption. AB - To exploit the adsorption capacity of commercial powdered activated carbon (PAC) and to improve the efficiency of Cr(VI) removal from aqueous solutions, the adsorption of Cr(VI) by commercial PAC and the countercurrent two-stage adsorption (CTA) process was investigated. Different adsorption kinetics models and isotherms were compared, and the pseudo-second-order model and the Langmuir and Freundlich models fit the experimental data well. The Cr(VI) removal efficiency was >80% and was improved by 37% through the CTA process compared with the conventional single-stage adsorption process when the initial Cr(VI) concentration was 50 mg/L with a PAC dose of 1.250 g/L and a pH of 3. A calculation method for calculating the effluent Cr(VI) concentration and the PAC dose was developed for the CTA process, and the validity of the method was confirmed by a deviation of <5%. PMID- 28985542 TI - Tiny but mighty: bacterial membrane vesicles in food biotechnological applications. AB - Membrane vesicle (MV) production is observed in all domains of life. Evidence of MV production accumulated in recent years among bacterial species involved in fermentation processes. These studies revealed MV composition, biological functions and properties, which made us recognize the potential of MVs in food applications as delivery vehicles of various compounds to other bacteria or the human host. Moreover, MV producing strains can deliver benefits as probiotics or starters in fermentation processes. Next to the natural production of MVs, we also highlight possible methods for artificial generation of bacterial MVs and cargo loading to enhance their applicability. We believe that a more in-depth understanding of bacterial MVs opens new avenues for their exploitation in biotechnological applications. PMID- 28985543 TI - Evaluation of interleukin-10 producing CD19+ B cells in human gingival tissue. AB - OBJECTIVE: This study aimed to evaluate IL-10 producing CD19+ B cells and to examine the correlation between these cells and the expression levels of IL 1beta, TNF-alpha, RANKL, and IL-10 cytokines in the gingival tissues of individuals with and without chronic periodontitis. DESIGN: Data were obtained from 20 patients with chronic periodontitis and 10 healthy controls. The gingival samples were analyzed by immunofluorescence, while real-time PCR and enzyme linked immunosorbent assays were performed to determine cytokine levels. RESULTS: The number of IL-10 producing CD19+ B cells and the expression levels of IL-10 were significantly higher in the inflamed gingival tissues than in the healthy tissues. A positive correlation between the expression levels of IL-10 and the number of IL-10 producing CD19+ B cells were observed. IL-1beta, TNF-alpha, and RANKL expression levels were significantly elevated in diseased gingivae compared to healthy tissues, and there was a positive correlation between the expression levels of these pro-inflammatory cytokines and the number of IL-10 producing CD19+ B cells. CONCLUSION: While IL-10 producing CD19+ B cells are present in the gingival tissues of patients with periodontal disease and of those with a healthy periodontium, the diseased gingival tissues had a much greater number of these cells than the healthy. The mRNA and protein levels of IL-10, IL-1beta, and RANKL, as well as mRNA levels of TNF-alpha, were positively correlated with the number of IL-10 producing CD19+ B cells, which highlights the importance of these factors in the development and progression of periodontitis. PMID- 28985544 TI - Spasticity and spastic dystonia: the two faces of velocity-dependent hypertonia. AB - BACKGROUND: Spasticity and spastic dystonia are two separate phenomena of the upper motor neuron syndrome. Spasticity is clinically defined by velocity dependent hypertonia and tendon jerk hyperreflexia due to the hyper-excitability of the stretch reflex. Spastic dystonia is the inability to relax a muscle leading to a spontaneous tonic contraction. Both spasticity and spastic dystonia are present in patients who are at rest; however, only patients with spasticity are actually able to kept their muscles relaxed prior to muscle stretch. The idea that has inspired the present work is that also in patients with spastic dystonia the stretch reflex is likely to be hyper-excitable. Therefore, velocity-dependent hypertonia could be mediated not only by spasticity, but also by spastic dystonia. METHODS: Tonic stretch reflexes in the rectus femoris muscle were evoked in 30 patients with multiple sclerosis showing velocity-dependent hypertonia of leg extensors and the habituation of the reflex was studied. Moreover, the capability of relax the muscle prior to muscle stretch (spastic dystonia) was also investigated. RESULTS: A tonic stretch reflex was evoked in all the enrolled patients. 73% of the patients were able to relax their rectus femoris muscle prior to stretch (spasticity). In the overwhelming majority of these patients, the tonic stretch reflex decreased during repeated stretches. In the remaining 27% of the subjects, the muscle was tonically activated prior to muscle stretch (spastic dystonia). In the patients in whom spastic dystonia progressively increased over the subsequent stretches (50% of the subjects with spastic dystonia), the habituation of the reflex was replaced by a progressive reflex facilitation. DISCUSSION: This study shows for the first time that velocity-dependent hypertonia can be caused by two distinct phenomena: spasticity and spastic dystonia. The habituation of the tonic stretch reflex, which is a typical feature of spasticity, is replaced by a reflex facilitation in the half of the subject with spastic dystonia. These preliminary findings suggest that differentiating the two types of velocity-dependent muscle hypertonia (spasticity and spastic dystonia) could be clinically relevant. PMID- 28985545 TI - Shaping innovation in health care: A content analysis of innovation policies in the English NHS, 1948-2015. AB - Governments around the world seek to design policies that enhance the innovative capacity of public service. Hence, identifying the underlying meanings attributed to innovation concepts in public policies is critical, as these very understandings inform not only the policy discourses, but also the overall institutional landscape regulating innovation activities. This paper examines such fundamental definitional aspects in the specific context of the National Health Service in England. For this purpose, it traces the evolution of the innovation concept in policy discourse based on the analysis of 21 key policy documents published or commissioned by the English Department of Health between 1948 and 2015. Systematic analysis of these texts reveals that policymakers' conception of healthcare innovation broadened considerably over time. English health innovation policy initially focused on basic biomedical research. Subsequently, it entered a transitional period, zeroing in on science- and technology-based innovation. Finally, this focus gradually shifted to a broader conception of innovation translating into health, economic, and service design benefits. PMID- 28985546 TI - Ovulation induction and controlled ovarian stimulation using letrozole gonadotropin combination: A single center retrospective cohort study. AB - OBJECTIVE: To assess the effect of letrozole in combination with low dose gonadotropins for ovulation induction in anovulatory infertility from polycystic ovary syndrome (PCOS) and controlled ovarian stimulation for endometriosis, and unexplained infertility patients. STUDY DESIGN: Retrospective cohort study in a setting of private Reproductive Endocrinology and Infertility Clinic affiliated with the University. Three hundred couples (650 cycles) requiring OI/COS for PCOS (92 patients, 195 cycles), endometriosis (89 patients, 217 cycles), and unexplained infertility (119 patients, 238 cycles). Patients received 2.5mg or 5mg letrozole for 5days (D3-D7) and recombinant follicle-stimulating hormone on alternating D3-D7 and human menopausal gonadotropin-highly purified alternating D5-D10 until growth of ideally 2 mature follicles. Ovulation was triggered with 10,000 IU of HCG. Maximum number of cycles per patient was four. RESULTS: Main outcome measures were clinical pregnancy rates, multiple order pregnancy rates, miscarriage rates, number of follicles and endometrial thickness on the day of HCG administration. The cumulative incidence of pregnancy was estimated as 35% (95%CI: 29%-41%) overall and was highest in patients with PCOS (36.6%), followed by unexplained infertility (34.6%) and endometriosis (32.5%). The pregnancy rates per cycle in PCOS, endometriosis and unexplained infertility patients were 17%, 13.2% and 17.2% respectively, no statistically significant difference between the groups. There were three twin pregnancies in PCOS, and one in unexplained infertility group. Monofolliculogenesis was noted in 48% of patients. CONCLUSION(S): Letrozole-low dose gonadotropins combination appears to be effective across different causes of infertility for superovulation. The letrozole-low dose gonadotropin combination resulted in high rate of monofolliculogenesis, low occurrence of multiple gestations and no case of OHSS or cycle cancellation. PMID- 28985547 TI - Efficacy of 5% imiquimod for the treatment of Vaginal intraepithelial neoplasia-A systematic review of the literature and a meta-analysis. AB - Vaginal intraepithelial neoplasia (VaIN) is an uncommon disease associated with HPV and is considered to be a precursor of vaginal carcinoma. To date, treatment recommendations vary with no universally accepted standard of care as best treatment modality. Nevertheless, 5% imiquimod appears to be a promising, alternative, non-invasive treatment option. To ascertain the efficacy of 5% imiquimod for the treatment of this rare condition, we conducted a systematic review and meta-analysis of the proportion of women who received 5% imiquimod with their complete response, HPV clearance and recurrence rates. A literature search was carried out throughout the PubMed, EMBASE, ClinicalTrials.gov and Cochrane Databases for relevant studies. We computed the summary proportions for complete response, HPV clearance and non-recurrence following administration of 5% imiquimod by random effects meta-analysis. Six articles reporting on 94 patients were included. The summary proportions of women with complete response and HPV clearance were 76.5% (95% CI 59.4-98.5) and 52.5% (95% CI 29.5-93.6) respectively. The summary proportion of women with non-recurrence appeared high (94.3% (95% CI 67.1-132)), yet not significant. Use of 5% imiquimod for the treatment of VaIN is associated with relatively high response rate, satisfactory HPV clearance, whilst the risk for VaIN recurrence appears low. PMID- 28985548 TI - The visibility of QSEN competencies in clinical assessment tools in Swedish nurse education. AB - BACKGROUND: Prospective nurses need specific and sufficient knowledge to be able to provide quality care. The Swedish Society of Nursing has emphasized the importance of the six quality and safety competencies (QSEN), originated in the US, in Swedish nursing education. PURPOSE: To investigate the visibility of the QSEN competencies in the assessment tools used in clinical practice METHOD: A quantitative descriptive method was used to analyze assessment tools from 23 universities. RESULTS AND CONCLUSION: Teamwork and collaboration was the most visible competency. Patient-centered care was visible to a large degree but was not referred to by name. Informatics was the least visible, a notable concern since all nurses should be competent in informatics to provide quality and safety in care. These results provide guidance as academic and clinical programs around the world implement assessment of how well nurses have developed these essential quality and safety competencies. PMID- 28985549 TI - How linear response shaped models of neural circuits and the quest for alternatives. AB - In the past decades, many mathematical approaches to solve complex nonlinear systems in physics have been successfully applied to neuroscience. One of these tools is the concept of linear response functions. However, phenomena observed in the brain emerge from fundamentally nonlinear interactions and feedback loops rather than from a composition of linear filters. Here, we review the successes achieved by applying the linear response formalism to topics, such as rhythm generation and synchrony and by incorporating it into models that combine linear and nonlinear transformations. We also discuss the challenges encountered in the linear response applications and argue that new theoretical concepts are needed to tackle feedback loops and non-equilibrium dynamics which are experimentally observed in neural networks but are outside of the validity regime of the linear response formalism. PMID- 28985550 TI - The many worlds hypothesis of dopamine prediction error: implications of a parallel circuit architecture in the basal ganglia. AB - Computational models of reinforcement learning (RL) strive to produce behavior that maximises reward, and thus allow software or robots to behave adaptively [1]. At the core of RL models is a learned mapping between 'states'-situations or contexts that an agent might encounter in the world-and actions. A wealth of physiological and anatomical data suggests that the basal ganglia (BG) is important for learning these mappings [2,3]. However, the computations performed by specific circuits are unclear. In this brief review, we highlight recent work concerning the anatomy and physiology of BG circuits that suggest refinements in our understanding of computations performed by the basal ganglia. We focus on one important component of basal ganglia circuitry, midbrain dopamine neurons, drawing attention to data that has been cast as supporting or departing from the RL framework that has inspired experiments in basal ganglia research over the past two decades. We suggest that the parallel circuit architecture of the BG might be expected to produce variability in the response properties of different dopamine neurons, and that variability in response profile may not reflect variable functions, but rather different arguments that serve as inputs to a common function: the computation of prediction error. PMID- 28985551 TI - The Stigma Resistance Scale: A multi-sample validation of a new instrument to assess mental illness stigma resistance. AB - Although associated with key recovery outcomes, stigma resistance remains under studied largely due to limitations of existing measures. This study developed and validated a new measure of stigma resistance. Preliminary items, derived from qualitative interviews of people with lived experience, were pilot tested online with people self-reporting a mental illness diagnosis (n = 489). Best performing items were selected, and the refined measure was administered to an independent sample of people with mental illness at two state mental health consumer recovery conferences (n = 202). Confirmatory factor analyses (CFA) guided by theory were used to test item fit, correlations between the refined stigma resistance measure and theoretically relevant measures were examined for validity, and test-retest correlations of a subsample were examined for stability. CFA demonstrated strong fit for a 5-factor model. The final 20-item measure demonstrated good internal consistency for each of the 5 subscales, adequate test-retest reliability at 3 weeks, and strong construct validity (i.e., positive associations with quality of life, recovery, and self-efficacy, and negative associations with overall symptoms, defeatist beliefs, and self-stigma). The new measure offers a more reliable and nuanced assessment of stigma resistance. It may afford greater personalization of interventions targeting stigma resistance. PMID- 28985552 TI - Differential symptomatology and functioning in borderline personality disorder across age groups. AB - There is increasing research aimed at addressing whether patients with borderline personality disorder (BPD) may exhibit variations in symptomatology and functioning according to their chronological age. The current study consisted of 169 outpatients diagnosed with BPD, who were divided into four age groups as follows: 16-25 years (n = 41), 26-35 years (n = 43), 36-45 years (n = 45), and 46 and more years (n = 40). Age groups were compared for symptomatology, normal personality traits, psychiatric comorbidities, functioning, and treatment-related features. The younger group had significantly higher levels of physical/verbal aggression and suicide attempts relative to the older group. Conversely, the older group had significantly greater severity of somatization, depression, and anxiety symptoms. In addition, the older group showed significantly greater functional impairment overall and across physical/psychological domains, specifically when compared to the younger group. Overall, these findings may suggest that age-related symptoms should be considered when diagnosing BPD. Also, functional impairments should be the target interventions for older BPD patients. PMID- 28985554 TI - Human Genetics: Questions, Challenges, and the Future. PMID- 28985553 TI - lncRNAs HIF1A-AS2 facilitates the up-regulation of HIF-1alpha by sponging to miR 153-3p, whereby promoting angiogenesis in HUVECs in hypoxia. AB - Angiogenesis serves as an important protective mechanism against ischemic stroke, because angiogenesis promotes the generation of collateral circulation and consequently improves the blood supply to cerebral infraction areas. Long noncoding RNAs (lncRNAs), which can act as a competing endogenous RNA, mediate protein-coding gene expression by sponging miRNA. Based on previous studies, the present study hypothesized that lncRNAs HIF1A-AS2 by sponging to miR-153-3p might regulate expression of HIF-1alpha and its down-stream targets, thereby influencing angiogenesis in hypoxia. Permanent middle cerebral artery occlusion (pMCAO) model was established in SD rats to explore the association between angiogenesis and expression profiles of miR-153-3p and HIF-1alpha in infraction areas. The effect of HIF1A-AS2 on angiogenesis was investigated in an in vitro study by using human umbilical vein endothelial cells (HUVECs). Results showed that angiogenesis was induced during pMCAO. pMCAO decreased miR-153-3p RNA level in infraction areas, but increased protein levels of HIF-1alpha, VEGFA and Notch1. HIF1A-AS2 was up-regulated in HUVECs in hypoxia. Luciferase reporter assay indicated that HIF1A-AS2 serves as a 'sponge' to miR-153-3p, which decreased the post-transcriptional silencing of HIF-1alpha by miR-153-3p. This function of HIF1A-AS2 facilitated the activation of HIF-1alpha/VEGFA/Notch1 cascades, by which HUVECs viability, migration ability and tube formation were promoted. These results suggest an enhanced angiogenesis in HUVECs. In short, HIF1A-AS2 facilitates the up-regulation of HIF-1alpha by sponging to miR-153-3p, whereby promoting angiogenesis in HUVECs in hypoxia. The present study revealed an important mechanism for understanding angiogenesis in hypoxia, thus laid theoretical basis for developing new strategy for the treatment of ischemic stroke. PMID- 28985555 TI - Gene Discovery for Complex Traits: Lessons from Africa. AB - The genetics of African populations reveals an otherwise "missing layer" of human variation that arose between 100,000 and 5 million years ago. Both the vast number of these ancient variants and the selective pressures they survived yield insights into genes responsible for complex traits in all populations. PMID- 28985556 TI - Land Plant Model Systems Branch Out. AB - The genome of the liverwort Marchantia polymorpha is an important step toward development of a new plant model system (Bowman et al., 2017). Liverworts may be the sister taxon to all other land plants, and the genome shows features that illuminate the ancestor of all land plants and give insights into how plant systems function and evolved. PMID- 28985557 TI - Guardians of the ERAD Galaxy. AB - The endoplasmic reticulum-associated degradation (ERAD) pathway facilitates the disposal of terminally misfolded proteins in the early secretory pathway yet spares folding intermediates from being destroyed. Zhang et al. report on a protein complex that acts as a guardian to protect these folding intermediates from being targeted for ERAD. PMID- 28985558 TI - Editing the Phenotype: A Revolution for Quantitative Genetics. AB - Quantitative trait genes have been difficult to analyze because of the subtle effects of their natural variation. Rodriguez-Leal et al. now develop a promoter editing approach to generate a range of effective alleles for analysis, providing an avenue to investigate complex interactions among such genes. PMID- 28985559 TI - Untangling the Web of Lymphoma Somatic Mutations. AB - In this issue of Cell, Reddy et al. report integrative genetic characterization of diffuse large B cell lymphomas (DLBCL), including large-scale exome capture, transcriptomes, CRISPR screens, and integrative clinical biomarker studies. This provides the first comprehensive overview of DLBCL biology and the basis for future precision medicine approaches to this disease. PMID- 28985560 TI - Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease. AB - Ferroptosis is a form of regulated cell death characterized by the iron-dependent accumulation of lipid hydroperoxides to lethal levels. Emerging evidence suggests that ferroptosis represents an ancient vulnerability caused by the incorporation of polyunsaturated fatty acids into cellular membranes, and cells have developed complex systems that exploit and defend against this vulnerability in different contexts. The sensitivity to ferroptosis is tightly linked to numerous biological processes, including amino acid, iron, and polyunsaturated fatty acid metabolism, and the biosynthesis of glutathione, phospholipids, NADPH, and coenzyme Q10. Ferroptosis has been implicated in the pathological cell death associated with degenerative diseases (i.e., Alzheimer's, Huntington's, and Parkinson's diseases), carcinogenesis, stroke, intracerebral hemorrhage, traumatic brain injury, ischemia-reperfusion injury, and kidney degeneration in mammals and is also implicated in heat stress in plants. Ferroptosis may also have a tumor suppressor function that could be harnessed for cancer therapy. This Primer reviews the mechanisms underlying ferroptosis, highlights connections to other areas of biology and medicine, and recommends tools and guidelines for studying this emerging form of regulated cell death. PMID- 28985562 TI - Cohesin Loss Eliminates All Loop Domains. AB - The human genome folds to create thousands of intervals, called "contact domains," that exhibit enhanced contact frequency within themselves. "Loop domains" form because of tethering between two loci-almost always bound by CTCF and cohesin-lying on the same chromosome. "Compartment domains" form when genomic intervals with similar histone marks co-segregate. Here, we explore the effects of degrading cohesin. All loop domains are eliminated, but neither compartment domains nor histone marks are affected. Loss of loop domains does not lead to widespread ectopic gene activation but does affect a significant minority of active genes. In particular, cohesin loss causes superenhancers to co-localize, forming hundreds of links within and across chromosomes and affecting the regulation of nearby genes. We then restore cohesin and monitor the re-formation of each loop. Although re-formation rates vary greatly, many megabase-sized loops recovered in under an hour, consistent with a model where loop extrusion is rapid. PMID- 28985561 TI - Insights into Land Plant Evolution Garnered from the Marchantia polymorpha Genome. AB - The evolution of land flora transformed the terrestrial environment. Land plants evolved from an ancestral charophycean alga from which they inherited developmental, biochemical, and cell biological attributes. Additional biochemical and physiological adaptations to land, and a life cycle with an alternation between multicellular haploid and diploid generations that facilitated efficient dispersal of desiccation tolerant spores, evolved in the ancestral land plant. We analyzed the genome of the liverwort Marchantia polymorpha, a member of a basal land plant lineage. Relative to charophycean algae, land plant genomes are characterized by genes encoding novel biochemical pathways, new phytohormone signaling pathways (notably auxin), expanded repertoires of signaling pathways, and increased diversity in some transcription factor families. Compared with other sequenced land plants, M. polymorpha exhibits low genetic redundancy in most regulatory pathways, with this portion of its genome resembling that predicted for the ancestral land plant. PAPERCLIP. PMID- 28985563 TI - Lactate Metabolism in Human Lung Tumors. AB - Cancer cells consume glucose and secrete lactate in culture. It is unknown whether lactate contributes to energy metabolism in living tumors. We previously reported that human non-small-cell lung cancers (NSCLCs) oxidize glucose in the tricarboxylic acid (TCA) cycle. Here, we show that lactate is also a TCA cycle carbon source for NSCLC. In human NSCLC, evidence of lactate utilization was most apparent in tumors with high 18fluorodeoxyglucose uptake and aggressive oncological behavior. Infusing human NSCLC patients with 13C-lactate revealed extensive labeling of TCA cycle metabolites. In mice, deleting monocarboxylate transporter-1 (MCT1) from tumor cells eliminated lactate-dependent metabolite labeling, confirming tumor-cell-autonomous lactate uptake. Strikingly, directly comparing lactate and glucose metabolism in vivo indicated that lactate's contribution to the TCA cycle predominates. The data indicate that tumors, including bona fide human NSCLC, can use lactate as a fuel in vivo. PMID- 28985564 TI - Cryo-EM Structures Reveal Mechanism and Inhibition of DNA Targeting by a CRISPR Cas Surveillance Complex. AB - Prokaryotic cells possess CRISPR-mediated adaptive immune systems that protect them from foreign genetic elements, such as invading viruses. A central element of this immune system is an RNA-guided surveillance complex capable of targeting non-self DNA or RNA for degradation in a sequence- and site-specific manner analogous to RNA interference. Although the complexes display considerable diversity in their composition and architecture, many basic mechanisms underlying target recognition and cleavage are highly conserved. Using cryoelectron microscopy (cryo-EM), we show that the binding of target double-stranded DNA (dsDNA) to a type I-F CRISPR system yersinia (Csy) surveillance complex leads to large quaternary and tertiary structural changes in the complex that are likely necessary in the pathway leading to target dsDNA degradation by a trans-acting helicase-nuclease. Comparison of the structure of the surveillance complex before and after dsDNA binding, or in complex with three virally encoded anti-CRISPR suppressors that inhibit dsDNA binding, reveals mechanistic details underlying target recognition and inhibition. PMID- 28985565 TI - Genetic Mapping and Biochemical Basis of Yellow Feather Pigmentation in Budgerigars. AB - Parrot feathers contain red, orange, and yellow polyene pigments called psittacofulvins. Budgerigars are parrots that have been extensively bred for plumage traits during the last century, but the underlying genes are unknown. Here we use genome-wide association mapping and gene-expression analysis to map the Mendelian blue locus, which abolishes yellow pigmentation in the budgerigar. We find that the blue trait maps to a single amino acid substitution (R644W) in an uncharacterized polyketide synthase (MuPKS). When we expressed MuPKS heterologously in yeast, yellow pigments accumulated. Mass spectrometry confirmed that these yellow pigments match those found in feathers. The R644W substitution abolished MuPKS activity. Furthermore, gene-expression data from feathers of different bird species suggest that parrots acquired their colors through regulatory changes that drive high expression of MuPKS in feather epithelia. Our data also help formulate biochemical models that may explain natural color variation in parrots. VIDEO ABSTRACT. PMID- 28985566 TI - Brain-wide Maps Reveal Stereotyped Cell-Type-Based Cortical Architecture and Subcortical Sexual Dimorphism. AB - The stereotyped features of neuronal circuits are those most likely to explain the remarkable capacity of the brain to process information and govern behaviors, yet it has not been possible to comprehensively quantify neuronal distributions across animals or genders due to the size and complexity of the mammalian brain. Here we apply our quantitative brain-wide (qBrain) mapping platform to document the stereotyped distributions of mainly inhibitory cell types. We discover an unexpected cortical organizing principle: sensory-motor areas are dominated by output-modulating parvalbumin-positive interneurons, whereas association, including frontal, areas are dominated by input-modulating somatostatin-positive interneurons. Furthermore, we identify local cell type distributions with more cells in the female brain in 10 out of 11 sexually dimorphic subcortical areas, in contrast to the overall larger brains in males. The qBrain resource can be further mined to link stereotyped aspects of neuronal distributions to known and unknown functions of diverse brain regions. PMID- 28985568 TI - A Prize for Cancer Prevention. PMID- 28985569 TI - SnapShot: Tissue Clearing. AB - Tissue clearing has become an important tool for the investigation of biological systems in three dimensions. However, many pioneering techniques were based on serendipitous discoveries. Next-generation clearing methods have been (re)designed with a better understanding of the chemistry and physics required to equalize the refractive index throughout a sample which prevents the random bending of light that clouds biological tissues. PMID- 28985570 TI - Triterpenes derived from hydrolyzate of total Gynostemma pentaphyllum saponins with anti-hepatic fibrosis and protective activity against H2O2-induced injury. AB - Gynostemma pentaphyllum is a popular functional food, and it is also used as a traditional medicine in Asia. In this study, five previously undescribed triterpenes, gypensapogenin M, gypensapogenin N, gypensapogenin O, gypensapogenin P, and gypensapogenin Q, together with five known compounds were isolated from the hydrolyzate of total G. pentaphyllum saponins. The bioassay data showed that all the triterpenes exhibited significant protective activity against H2O2 induced myocardial cell injury and anti-hepatic fibrosis activity. Taken together, the discovery of these triterpenes from the hydrolyzate of total G. pentaphyllum saponins expands its use as a functional food for preventing myocardial injury and liver fibrosis. PMID- 28985571 TI - Alkaloid constituents from Viola tianschanica. AB - Eighteen previously undescribed alkaloids, tishaviolamines A-J, including eight pairs of enantiomers, together with two known benzylisoquinoline alkaloids, (-) bicuculline and (-)-corlumine, were isolated from Viola tianschanica. Among them, tishaviolamine A-E were demonstrated to possess three types of unpresented skeletons. The structures of these alkaloids were established by comprehensive analyses of the 1D, 2D-NMR and (+)HRESIMS data. The absolute configurations of enantiomers were determined by comparing their calculated ECD spectra with the experimental ones. The menin-mixed lineage leukemia 1 protein-protein interaction inhibitory effect of the isolated compounds were also measured. PMID- 28985567 TI - Genetic and Functional Drivers of Diffuse Large B Cell Lymphoma. AB - Diffuse large B cell lymphoma (DLBCL) is the most common form of blood cancer and is characterized by a striking degree of genetic and clinical heterogeneity. This heterogeneity poses a major barrier to understanding the genetic basis of the disease and its response to therapy. Here, we performed an integrative analysis of whole-exome sequencing and transcriptome sequencing in a cohort of 1,001 DLBCL patients to comprehensively define the landscape of 150 genetic drivers of the disease. We characterized the functional impact of these genes using an unbiased CRISPR screen of DLBCL cell lines to define oncogenes that promote cell growth. A prognostic model comprising these genetic alterations outperformed current established methods: cell of origin, the International Prognostic Index comprising clinical variables, and dual MYC and BCL2 expression. These results comprehensively define the genetic drivers and their functional roles in DLBCL to identify new therapeutic opportunities in the disease. PMID- 28985572 TI - Post photosynthetic carbon partitioning to sugar alcohols and consequences for plant growth. AB - The occurrence of sugar alcohols is ubiquitous among plants. Physiochemical properties of sugar alcohols suggest numerous primary and secondary functions in plant tissues and are often well documented. In addition to functions arising from physiochemical properties, the synthesis of sugar alcohols may have significant influence over photosynthetic, respiratory, and developmental processes owing to their function as a large sink for photosynthates. Sink strength is demonstrated by the high concentrations of sugar alcohols found in plant tissues and their ability to be readily transported. The plant scale distribution and physiochemical function of these compounds renders them strong candidates for functioning as stress metabolites. Despite this, several aspects of sugar alcohol biosynthesis and function are poorly characterised namely: 1) the quantitative characterisation of carbon flux into the sugar alcohol pool; 2) the molecular control governing sugar alcohol biosynthesis on a quantitative basis; 3) the role of sugar alcohols in plant growth and ecology; and 4) consequences of sugar alcohol synthesis for yield production and yield quality. We highlight the need to adopt new approaches to investigating sugar alcohol biosynthesis using modern technologies in gene expression, metabolic flux analysis and agronomy. Combined, these approaches will elucidate the impact of sugar alcohol biosynthesis on growth, stress tolerance, yield and yield quality. PMID- 28985573 TI - Antibody-based immunotherapy of aciclovir resistant ocular herpes simplex virus infections. AB - The increasing incidence of aciclovir- (ACV) resistant strains in patients with ocular herpes simplex virus (HSV) infections is a major health problem in industrialized countries. In the present study, the humanized monoclonal antibody (mAb) hu2c targeting the HSV-1/2 glycoprotein B was examined for its efficacy towards ACV-resistant infections of the eye in the mouse model of acute retinal necrosis (ARN). BALB/c mice were infected by microinjection of an ACV-resistant clinical isolate into the anterior eye chamber to induce ARN and systemically treated with mAb hu2c at 24h prior (pre-exposure prophylaxis) or at 24, 40, and 56h after infection (post-exposure immunotherapy). Mock treated controls and ACV treated mice showed pronounced retinal damage. Mice treated with mAb hu2c were almost completely protected from developing ARN. In conclusion, mAb hu2c may become a reliable therapeutic option for drug/ACV-resistant ocular HSV infections in humans in order to prevent blindness. PMID- 28985574 TI - Full genomic characterization of California serogroup viruses, genus Orthobunyavirus, family Peribunyaviridae including phylogenetic relationships. AB - Thorough molecular characterization of reference viruses supports the detection of emerging human pathogens as well as studies of evolutionary relationships. However, full characterization of the tripartite RNA genomes of many viruses of the clinically important family Peribunyaviridae remains incomplete, making it difficult to identify emerging strains. Here, we report the full genome sequences of nine viruses belonging to the California serogroup and describe multi-segment analyses of these and previously published California serogroup strain data to determine the role of segment reassortment in the evolution of this serogroup. Phylogenetic trees from the small, medium, and large segments suggest long term, independent evolution of the majority of strains. However, trees from each segment were not entirely congruent and evidence of reassortment among some strains is presented. Of unique interest, the L segment phylogeny reveals divergent branching patterns for encephalitic versus non-encephalitic viruses in both major clades of the California serogroup. PMID- 28985576 TI - Plant membrane-protein mediated intracellular traffic of fatty acids and acyl lipids. AB - In plants, de novo synthesis of fatty acids (FAs) occurs in plastids, whereas assembly and modification of acyl lipids is accomplished in the endoplasmic reticulum (ER) and plastids as well as in mitochondria. Subsequently, lipophilic compounds are distributed within the cell and delivered to their destination site. Thus, constant acyl-exchanges between subcellular compartments exist. These can occur via several modes of transport and plant membrane-intrinsic proteins for FA/lipid transfer have been shown to play an essential role in delivery and distribution. Lately, substantial progress has been made in identification and characterization of transport proteins for lipid compounds in plant organelle membranes. In this review, we focus on our current understanding of protein mediated lipid traffic between organelles of land plants. PMID- 28985575 TI - Research progress in modern structure of platinum complexes. AB - Since the antitumor activity of cisplatin was discovered in 1967 by Rosenberg, platinum-based anticancer drugs have played an important role in chemotherapy in clinic. Nevertheless, platinum anticancer drugs also have caused severe side effects and cross drug resistance which limited their applications. Therefore, a significant amount of efforts have been devoted to developing new platinum-based anticancer agents with equal or higher antitumor activity but lower toxicity. Until now, a large number of platinum-based complexes have been prepared and extensively investigated in vitro and in vivo. Among them, some platinum-based complexes revealing excellent anticancer activity showed the potential to be developed as novel type of anticancer agents. In this account, we present such platinum-based anticancer complexes which owning various types of ligands, such as, amine carrier ligands, leaving groups, reactive molecule, steric hindrance groups, non-covalently binding platinum (II) complexes, Platinum(IV) complexes and polynuclear platinum complexes. Overall, platinum-based anticancer complexes reported recently years upon modern structure are emphasized. PMID- 28985577 TI - Characteristics of clinical measurements between biomechanical responders and non responders to a shoe designed for knee osteoarthritis. AB - PURPOSE: The purpose of this study was to investigate the characteristics of biomechanical and clinical measurements in relation to the knee adduction moment when wearing a standard shoe and a shoe design for individuals with knee osteoarthritis (Flex-OA). METHODS: Kinematic and kinetic data were collected from thirty-two healthy individuals (64 knees) using a ten camera motion analysis system and four force plates. Subjects performed 5 walking trials under the two conditions and the magnitude of individuals' biomechanical responses where explored in relation to the clinical assessment of the Foot Posture Index, hip rotation range, strength of hip rotators, and active ankle-foot motion, all of which have been described as possible compensation mechanisms in knee osteoarthritis. RESULTS: Significant reductions in the first peak of the knee adduction moment (KAM) during stance phase (9.3%) were recorded (p<0.0001). However, despite this difference, 22 of 64 knees showed either no change or an increased KAM, indicating a non-response or negative-response to the Flex-OA shoe. Significant differences were observed between the responder and non responder subgroups in the hip rotation range ratio (p=0.044) and the hip rotators strength ratio (p=0.028). CONCLUSION: Significant differences were seen in clinical assessments of hip rotation range and hip rotator strength between responders and non-responders using a cut-off of 0.02Nm/kg change in the KAM. PMID- 28985578 TI - Standing or swaying to the beat: Discrete auditory rhythms entrain stance and promote postural coordination stability. AB - Humans seem to take social and behavioral advantages of entraining themselves with discrete auditory rhythms (e.g., dancing, communicating). We investigated the benefits of such an entrainment on posture during standing (spontaneous entrainment) and during a whole-body swaying task (intentional synchronization). We first evaluated how body sway was entrained by different auditory metronome frequencies (0.25, 0.5, and 1.0Hz). We then assessed the stabilizing role of auditory rhythms on postural control, characterized in a dynamical systems perspective by informational anchoring of the head (local stabilization) and fewer transitions from in-phase to anti-phase ankle-hip coordination (global stabilization). Our results revealed in both situations an entrainment of postural movements by external rhythms. This entrainment tended to be more effective when the metronome frequency (0.25Hz) was close to the dominant sway frequency. Particularly, we found during intentional synchronization that head movements were less variable when paced by a slower beat (informational anchoring), and that phase transitions between the two stable patterns in postural dynamics were delayed. Our findings demonstrate that human bipedal posture can be actively or spontaneously modulated by an external discrete auditory rhythm, which might be exploited for the purpose of learning and rehabilitation. PMID- 28985579 TI - Metformin and insulin impact on clinical outcome in patients with advanced hepatocellular carcinoma receiving sorafenib: Validation study and biological rationale. AB - PURPOSE: In 2015, we published a study on a small series of patients with hepatocellular carcinoma (HCC) treated chronically with metformin for type II diabetes mellitus (DM2) who showed a poorer response to sorafenib. The aim of the present study was to validate the prognostic significance of metformin in HCC patients treated with sorafenib, providing a biological rationale for the mechanism of resistance to sorafenib in patients on chronic metformin therapy, and to clarify the role of sirtuin-3 (SIRT-3), a protein involved in metabolic diseases and acknowledged as a tumour suppressor in HCC, in this resistance. PATIENTS AND METHODS: We analysed 279 patients consecutively treated with sorafenib for the clinical analysis. Of the 86 (30%) patients with DM2, 52 (19%) were on chronic treatment with metformin and 34 (12%) with insulin. We included 43 patients with HCC for the biological study: 19 (44.1%) were diabetic and 14 (73.7%) of these received metformin for DM2. SIRT-3 expression was investigated by immunohistochemistry (IHC) in formalin-fixed and paraffin-embedded (FFPE) samples. RESULTS: In HCC patients undergoing chronic treatment with metformin, the use of sorafenib was associated with poor progression-free survival (PFS) and overall survival (OS) (1.9 and 6.6 months, respectively) compared to 3.7 months and 10.8 months, respectively, for patients without DM2 and 8.4 months and 16.6 months, respectively, for patients on insulin (P < .0001). We also observed that SIRT-3 protein expression was significantly higher in patients treated with metformin than in those not taking this medication (65% versus 25%, respectively) (P = .013). CONCLUSIONS: Our findings could be attributed to increased tumour aggressiveness and resistance to sorafenib caused by chronic treatment with metformin. PMID- 28985580 TI - Implementation of a nightly bedtime routine: How quickly do things improve? AB - BACKGROUND: Institution of a consistent bedtime routine has been demonstrated to improve sleep in young children within two weeks. However, no studies have investigated the rate of this change and when most change occurs. The purpose of this study was to examine the nightly change in infant sleep and maternal perceptions after implementing a bedtime routine. METHODS: Mothers (n=134) and their infant (8-18 months) were randomly assigned to implementation of a bedtime routine intervention for a two-week period. RESULTS: Two-level piecewise linear growth models showed that the intervention resulted in the most rapid change in the first three nights of the intervention across sleep outcomes, including sleep onset latency, the frequency and duration of nighttime awakenings, sleep consolidation, and maternal perceptions of bedtime ease, sleep quality, and infant mood. No significant additional improvement in sleep onset latency emerged after these first three nights, whereas small additional improvements occurred for all other outcomes throughout the remainder of the intervention period. CONCLUSIONS: These results indicate that sleep disturbances in infants and toddlers can be quickly ameliorated within just a few nights after implementation of a consistent bedtime routine, including a bath, massage, and quiet activities. Future research should consider the potential mechanisms behind these relatively fast improvements in sleep, such as reduced household chaos or physiological changes (e.g. core body temperature, cortisol). PMID- 28985581 TI - Postpartum tubal ligation: A retrospective review of anesthetic management at a single institution and a practice survey of academic institutions. AB - STUDY OBJECTIVE: The primary aim was to evaluate institutional anesthetic techniques utilized for postpartum tubal ligation (PPTL). Secondarily, academic institutions were surveyed on their clinical practice for PPTL. DESIGN: An institutional-specific retrospective review of patients with ICD-9 procedure codes for PPTL over a 2-year period was conducted. Obstetric anesthesia fellowship directors were surveyed on anesthetic management of PPTL. SETTING: Labor and delivery unit. Internet survey. PATIENTS: 202 PPTL procedures were reviewed. 47 institutions were surveyed; 26 responses were received. MEASUREMENTS: Timing of PPTL, anesthetic management, postoperative pain and length of stay. MAIN RESULTS: There was an epidural catheter reactivation failure rate of 26% (18/69 epidural catheter reactivation attempts). Time from epidural catheter insertion to PPTL was a significant factor associated with failure: median [IQR; range] time for successful versus failed epidural catheter reactivation was 17h [10-25; 3-55] and 28h [14-33; 5-42], respectively (P=0.028). Epidural catheter reactivation failure led to significantly longer times to provide surgical anesthesia than successful epidural catheter reactivation or primary spinal technique: median [IQR] 41min [33-54] versus 15min [12-21] and 19min [15-24], respectively (P<0.0001). Fifty-eight percent (15/26) of respondents routinely leave the labor epidural catheter in-situ if PPTL is planned. Sixty-five percent (17/26) and 7% (2/26) would not attempt to reactivate the epidural catheter for PPTL if >8h and >24h post-delivery, respectively. CONCLUSIONS: Epidural catheter reactivation failure increases with longer intervals between catheter placement and PPTL. Failed epidural catheter reactivation increases anesthetic and operating room times. Our results and the significant variability in practice from our survey suggest recommendations on the timing and anesthetic management are needed to reduce unfulfilled PPTL procedures. PMID- 28985582 TI - Reversal of trend in near infrared spectroscopy [NIRS] values in a patient with carotid artery stenosis. PMID- 28985583 TI - Surgeon assisted quadratus lumborum block - 'Gaurav-Aditi' technique case series. PMID- 28985584 TI - Strategies to prevent ischemic optic neuropathy following major spine surgery: A narrative review. AB - Postoperative vision loss following a major spine operation is a rare but life changing event. Most of reports have been linked to ischemic optic neuropathy, and patients undergoing surgery for scoliosis correction or posterior lumbar fusion seem to be at the highest risk. Despite that some key risk factors have been identified, much of the pathophysiology still remain unknown. In fact, whereas only a minority of patients at high risk will present this complication, others with similar risk factors undergoing different procedures may not develop it at all. On the other hand, even when all preventive measures have been taken, ischemic optic neuropathy may still occur. Therefore, it is appropriate for clinicians involved in these cases to inform their patients about the existence of a small but unpredictable risk of vision loss. Since ischemic optic neuropathy is deemed to be the leading cause of vision loss in the context of major spine surgery in prone position, this review will be focused on its main aspects related to the frequency, diagnosis, predisposing factors, and prevention. Regrettably, no treatment has been proved to be effective for this condition. PMID- 28985585 TI - Anesthetic management for retrieval of a large aspirated denture in a patient with Parkinson's disease. PMID- 28985586 TI - Effects of a stand-alone web-based electronic screening and brief intervention targeting alcohol use in university students of legal drinking age: A randomized controlled trial. AB - BACKGROUND: Many intervention efforts targeting student drinking were developed to address US college students, which usually involves underage drinking. It remains unclear, if research evidence from these interventions is generalizable to university and college students of legal drinking age, e.g., in Europe. OBJECTIVE: To evaluate the effectiveness of a translated and adapted version of the eCHECKUP TO GO, applied as stand-alone web-based electronic screening and brief intervention (e-SBI), in German university students at risk for hazardous drinking. METHODS: A fully automated web-based two-arm parallel-group randomized controlled trial was conducted. Participants were randomized to an e-SBI or assessment-only (AO) condition. The current paper analyzed students with baseline AUDIT-C scores >=3 for women and >=4 for men (sample at baseline: e-SBI [n=514], AO [n=467]; 3-month follow-up: e-SBI [n=194], AO [n=231]; 6-month follow-up: e SBI [n=146], AO [n=200]). The primary outcome was prior four weeks' alcohol consumption. Secondary outcomes were frequency of heavy drinking occasions, peak blood alcohol concentration, and number of alcohol-related problems. RESULTS: Mixed linear model analyses revealed significant interaction effects between groups and time points on the primary outcome after 3 and 6months. Compared to students in the AO condition, students in the e-SBI condition reported consuming 4.11 fewer standard drinks during the previous four weeks after 3months, and 4.78 fewer standard drinks after 6months. Mixed results were found on secondary outcomes. CONCLUSIONS: The results indicate that evidence on and knowledge of web based e-SBIs based on US college student samples is transferable to German university students of legal drinking age. However, knowledge of what motivates students to complete programs under voluntary conditions, although rare, is needed. PMID- 28985587 TI - Cerebrospinal fluid D-serine concentrations in major depressive disorder negatively correlate with depression severity. AB - BACKGROUND: D-serine is an endogenous co-agonist of N-methyl-D-aspartate receptor (NMDAR) and plays an important role in glutamate neurotransmission. Several studies suggested the possible involvement of D-serine related in the pathophysiology of psychiatric disorders including major depression disorders (MDD). We tried to examine whether cerebrospinal fluid (CSF) or plasma D-serine concentrations are altered in MDD and whether D-serine concentrations correlated with disease severity. METHODS: 26 MDD patients and 27 healthy controls matched for age, sex and ethnicity were enrolled. We measured amino acids in these samples using by high-performance liquid chromatography with fluorometric detection. RESULTS: D-serine and L-serine, precursor of D-serine, levels in CSF or plasma were not significantly different in patients of MDD compared to controls. Furthermore, a significant correlation between D-serine levels in CSF and Hamilton Depression Rating Scale (HAMD)-17 score was observed (r = -0.65, p = 0.006). Furthermore, we found a positive correlation between CSF D-serine and HVA concentrations in MDD patients (r = 0.54, p = 0.007). CSF D-serine concentrations were correlated with those of plasma in MDD (r = 0.61, p = 0.01) but not in controls. In CSF, we also confirmed a significant correlation between D-serine and L-serine levels in MDD (r = 0.72, p < 0.0001) and controls (r = 0.70, p < 0.0001). CONCLUSIONS: The study has some limitations; sample size was relatively small and most patients were medicated. We revealed that CSF D-serine concentrations were correlated with depression severity and HVA concentrations and further investigation were required to reveal the effect of medication and disease heterogeneity. PMID- 28985588 TI - Inter- and intra-specific competition of duckweed under multiple heavy metal contaminated water. AB - The influences of intra- and inter-species competition on ecosystems are poorly understood. Lemna aequinoctialis and Spirodela polyrhiza were used to assess the effects of exposure to different concentrations of multiple heavy metals (copper cadmium-zinc), when the plants were grown in mixed- or mono-culture. Parameters assessed included relative growth rate (RGR), content of chlorophyll, glutathione (GSH), malondialdehyde (MDA), as well as the activity of catalase (CAT), superoxide dismutase (SOD) and peroxidase (POD). Inter-specific competition was affected by metal concentration, with results indicating that inter-specific competition significantly affected duckweed growth and metal uptake in different heavy metal exposure conditions. Inter-specific competition increased growth rate of duckweed under high metal concentrations, although when compared with intra specific competition, it caused no obvious differences under low metal concentrations. The growth of L. aequinoctialis was further increased in mixed culture when exposed to high metal concentrations, with inter-specific competition increasing the content of cadmium and zinc, while decreasing copper content of L. aequinoctialis compared with under intra-specific conditions. Conversely, inter-specific competition increased the content of copper and cadmium of S. polyrhiza, without causing obvious differences in zinc accumulation under high ambient concentrations. Under high metal conditions, inter-specific competition increased antioxidant enzyme activities in duckweed species, increasing resistance to heavy metals. Results show that inter-specific competition makes duckweed develop mechanisms to increase fitness and survival, such as enhancement of antioxidant enzyme activities, rather than limiting metal uptake when exposed to high concentrations of multiple metals. PMID- 28985590 TI - A new turn-on fluorimetric method for the rapid speciation of Cr(III)/Cr(VI) species in tea samples with rhodamine-based fluorescent reagent. AB - A new fluorimetric method with rhodamine-based fluorescent agent was developed for the rapid speciation of Cr(III)/Cr(VI) in tea, soil and water samples. The system, which utilizes a fluorescent reagent, was used for the first time after synthesis/characterization of 3',6'-bis(diethylamino)-2-{[(1E)-(2,4 dimethoxyphenyl)methylene] amino}spiro[isoindole-1,9'-xanthen]-3(2H)-one (BDAS). The reagent responds instantaneously at room temperature in a 1:1 stoichiometric manner to the amount of Cr(III). The selectivity of this system for Cr(III) over other metal ions is remarkably high, and its sensitivity is below 0.01mgL-1 in aqueous solutions which enables a simplification without any pretreatment of the real sample. The method has a wide linear range of 0.1-10mgL-1 and a detection limit of 0.15MUgL-1 for Cr(III) while the relative standard deviation was 0.1% for 0.1mgL-1 Cr(III) concentration. The results of detection and recovery experiments for Cr(III) in tea, soil and water were satisfactory, indicating that the method has better feasibility and application potential in the routine determination and speciation of Cr(III)/Cr(VI). The results of analysis of the certified reference material (INCT-TL-1 tea sample and CWW-TM-D waste water) are in good agreement with the certified value. PMID- 28985589 TI - Screening for psychological distress using the Patient Health Questionnaire Anxiety and Depression Scale (PHQ-ADS): Initial validation of structural validity in dialysis patients. AB - OBJECTIVE: To validate the factor structure of the Patient Health Questionnaire Anxiety and Depression Scale (PHQ-ADS)- which is a composite measure of depression and anxiety using the Patient Health Questionnaire-9 and Generalised Anxiety Disorder Scale (GAD-7), in a sample of haemodialysis patients. METHOD: Screening data (n=182) used to select entry into a feasibility study of an online cognitive-behavioural therapy intervention for distress in dialysis patients were analysed here. Structural validity of the PHQ-ADS was evaluated using confirmatory factor analysis (CFA), assessing alternative models including a bi factor model. In the bi-factor model all items from the PHQ-9 and GAD-7 (16-items in total) were loaded onto a general distress factor. Respective items of the PHQ 9 and GAD-7 were specified as subgroup factors. Omega-hierarchical was calculated to indicate the level of saturation of a multidimensional scale by a general factor. Construct validity was determined against the Brief Illness Perception Questionnaire. RESULTS: A bi-factor PHQ-ADS model had good fit to the data (chi square=96.1, p=0.26, CFI=0.99; TLI=0.99; RMSEA=0.02). The general distress factor accounted for approximately 84% of the explained variance (omega-h=0.90). Distress scores were significantly higher in females compare with males. There was a significant association between distress and negative illness perceptions (r=0.58, p<0.01). CONCLUSIONS: The PHQ-ADS appears to have good structural validity in haemodialysis patients and is sufficiently unidimensional to warrant the use of a total distress score. A full psychometric analysis of the PHQ-ADS in a larger sample of dialysis patients is warranted. PMID- 28985591 TI - Antiphospholipid syndrome and recurrent miscarriage: A systematic review and meta analysis. AB - Antiphospholipid syndrome (APS) is an autoimmune condition that is associated with thrombosis and morbidity in pregnancy. The exact mechanisms by which these associations occur appear to be heterogeneous and are not yet well understood. The aim of this study was to identify and analyze publications in recent years to better understand the diagnosis and its contribution to monitoring APS among women with recurrent miscarriage (RM). This systematic review and meta-analysis was conducted using the PubMed and Web of Knowledge databases, with articles published between 2010 and 2014, according to the PRISMA statement. Of the 85 identified studies, nine were selected. Most of the studies reported an association between recurrent miscarriage and specific antiphospholipid antibodies, as anticardiolipin antibodies (aCL), lupus anticoagulant (LA), anti beta2-glycoprotein I antibodies (abeta2GPI) and antiphosphatidylserine (aPS), which showed a relationship with RM. The main result of the meta-analysis revealed association between antiphospholipid antibodies (aPLs) and/or APS compared to the patients with RM (OR: 0.279; 95% CI: 0.212-0.366) and APS cases compared to the patients with RM (OR: 0.083; 95% CI: 0.036-0.189). High heterogeneity among these studies (I2=100.0%, p <0.001) was observed. In addition, there was no significant publication bias across studies according to Begg's test (p=0.230), although Egger's test (p=0.037) suggests significant publication bias. The funnel plot was slightly asymmetrical. Systematic review and meta-analysis demonstrated a positive association between antiphospholipid antibodies and/or antiphospholipid syndrome in patients with recurrent miscarriage. PMID- 28985592 TI - Pharmacological thrombolysis for acute ischemic stroke treatment: Gender differences in clinical risk factors. AB - BACKGROUND: In a stroke population, women have a worse outcome than men when untreated. In contrast, there is no significant difference in treated patients. In this study, we determined whether clinical variables represent a promising approach to assist in the evaluation of gender differences in a stroke population. METHODS: We analyzed data from ischemic stroke patients' >=18 years old from the stroke registry on rtPA administration and identified gender differences in clinical factors within inclusion and exclusion criteria in a stroke population that received rtPA. Multivariate analysis was used to adjust for patient demographic and clinical variables. RESULTS: Of the 241 eligible stroke patients' thrombolytic therapy, 49.4% were females and 50.6% were males. Of the 422 patients that did not receive rtPA, more women (235) were excluded from rtPA than men (187) (P<0.05). In the male population, exclusion from rtPA was associated with history of a previous stroke (P<0.05, OR=2.028), hypertension (P<0.05, OR=0.519), and NIH stroke score (P<0.0001, OR=0.893). In female stroke patients, exclusion from rtPA was associated with previous history of stroke (P<0.05, OR=2.332), diabetes (P<0.05, OR=1.88) and NIH stroke score (P<0.05, OR=0.916). CONCLUSIONS: Despite similarities in different areas of stroke care for both men and women, more women with diabetes, previous history of stroke and higher NIH scores are more likely to be excluded from thrombolytic therapy. Men with a previous history of stroke, hypertension and higher NIH scores are more likely to be excluded rtPA even after adjustment for confounding variables. PMID- 28985593 TI - Effects of chilled-then-frozen storage (up to 52weeks) on an indicator of protein oxidation and indices of protein degradation in lamb M. longissimus lumborum. AB - This study investigated the protein oxidation properties of lamb following chilled-then-frozen storage. Experimental (n=360) M. longissimus lumborum (LL) were randomly sampled from the boning room of a commercial Australian abattoir, at 24h post mortem, and assigned to five chilled storage periods (0, 2, 4, 6 and 8weeks) and six subsequent frozen storage periods (0, 4, 8, 12, 24 and 52weeks). Upon completion of each storage treatment combination, corresponding LL were sub sectioned and analysed for carbonyl content, protein solubility, nitrate/nitrite content, particle size analysis and estimated myoglobin fractions. The association between these protein measures and shear force was also explored. During chilled storage, particle size and sarcoplasmic protein solubility decreased which indicated protein degradation, while frozen storage only affected myoglobin oxidation. Tenderness was best explained by decreased particle size, decreased deoxymyoglobin and increased oxymyoglobin. No carbonyl effects were observed. It can be concluded that, according to these analyses, that in chilled then-frozen lamb carbonyl formation was negligible. PMID- 28985594 TI - The effect of beam slope on the perception of melodic contour. AB - Musical score reading is a complex task, which involves attending and interpreting multiple visual constituents that are graphically congested. The present investigation examined the 'beam', which although consistently found in music notation, is typically considered as providing no more information than marking metric boundaries (i.e., chunking). However, we provide evidence here that beams enhance visual perception of contour. In Study 1, a Stroop-like paradigm was used in which participants were required to judge the direction of notes or the beam in a compound figure; the two dimensions were either congruent or incongruent. A congruency effect was observed in both tasks, confirming that both notes and beam are processed automatically during score reading. In Study 2, an additional auditory stimulus was presented. The results not only replicated the findings of Study 1, but showed that beams affect both visual and auditory perception. Finally, group differences surfaced: musicians were more affected by the direction of notes than non-musicians when attending to beams, but the effect of beams on judging note direction was comparable in both groups. The implications for understanding musical score reading - specifically issues related to melodic contour - are discussed. PMID- 28985595 TI - Investigation of the use of luminescent markers as gunshot residue indicators. AB - The addition of luminescent markers into ammunition cartridges is an appealing proposal to achieve a greater individual identification of the ammunition. The lanthanide elements present in these luminescent materials act as characteristic chemical markers that, also, offer the great benefit of making gunshot residues (GSR) collection easier. Although the use of luminescent markers offers numerous advantages, and can be a reliable future option in the cartridge ammunition market, little or nothing is known about the interaction of the marker with the ammunition compounds after the shot. For the forensic laboratories, it is of utmost importance to anticipate the commercialization of tagged luminescent ammunition by knowing the type of particles produced after the discharge. That is, to investigate if markers merge with GSR to form single particles or, on the contrary, they form individual particles that travel separately from the GSR particles. In this work, conventional ammunition cartridges tagged with two types of luminescent markers were shot. Then, the particles produced were visualized under UV light on the floor, clothing targets and the shooter. The luminescent particles spread over the floor determined the shooter position and the bullet trajectory. The illumination of the shot targets allows the visualization of the GSR patterns only using a portable UV lamp, avoiding the use of colorimetric test. The GSR particles were collected and subjected to SEM-EDX and Raman spectroscopy analysis to get information about their inorganic and organic composition. The results indicated that part of the marker and the GSR merge and travel together. With this, particles composed by the marker and propellant organic compounds can be identified by Raman spectroscopy, and the unequivocal identification of the GSR and the marker can be achieved by SEM-EDX. Consequently, the luminescent particles detected under UV light improve the evidence collection and offer information about the GSR and the marker. Additionally, this study support the use of luminescent ammunition to study, for example, the transfer or persistence of GSR. PMID- 28985596 TI - Synthesis and characterization of polysulfone/graphene oxide nano-composite membranes for removal of bisphenol A from water. AB - Bisphenol A (BPA) is an emerging contaminant of water resources that disrupts endocrine function. Attempts are continuing to develop cost-effective methods to remove BPA from water environments. The aim of this study was to prepare and characterize polysulfone/graphene oxide nano-composite membranes for removal of BPA from water. Three membranes were synthetized using phase inversion method: polysulfone membrane as PSF and two polysulfone/graphene oxide nano-composite membranes with graphene oxide (GO) weight ratios of 0.4 and 1.0% as PSF/GO 0.4% and PSF/GO 1.0%, respectively. The membrane characteristics including morphology, surface roughness, pore size, zeta potential and presence of functional groups were determined using field emission scanning electron microscopy, atomic force microscopy, streaming potential, and attenuated total reflectance Fourier transform infrared spectroscopy techniques. Inclusion of GO remarkably increased permeate flux of the membranes, so that pure water flux of PSF, PSF/GO 0.4% and PSF/GO 1.0% at operating pressure of 2 bar was determined 226, 449 and 512 L/m2 h, respectively. The membrane PSF/GO 0.4% with the most negative zeta potential ( 10.46 mV) and the highest BPA removal efficiency was determined as the optimal membrane. The optimum conditions of input pressure, operating time, initial concentration of BPA, and pH for BPA removal efficiency by PSF/GO 0.4% were determined using surface response methodology to be 1.02 bar, 10.6 min, 7.5 mg/L, and 5.5, respectively. By optimizing the conditions of operating parameters, experimental BPA removal efficiency by PSF/GO 0.4% reached to as high as 93%. PMID- 28985597 TI - Human health risk assessment of ground water contaminated with petroleum PAHs using Monte Carlo simulations: A case study of an Indian metropolitan city. AB - Underground pipelines are frequently used to transport petroleum fuels, through industrial as well as residential zones. Chennai is one of the four largest metropolitan cities of India. The region of interest in this study is located in the northern part of the Chennai. Ground water of this area was contaminated with polyaromatic hydrocarbons (PAHs) from the leaking oil storage tanks and pipe lines. Health risk assessment was conducted for exposure to PAHs in the ground water using incremental life time cancer risk (ILCR) models coupled with benzo[a]pyrene toxic equivalent method. The exposure pathways considered in this study were direct water ingestion and dermal contact under residential scenario. Exposure input parameters were transformed to statistical parameters using lognormal/uniform distributions and resultant probabilities of cancer risk were estimated by performing Monte Carlo simulations. Preliminary remediation goals were predicted using the combination of the cancer risk models of all the exposure routes with the consideration of high-safety risk of 1-in-1 million. Results showed that the cancer risk is predominantly contributed (greater than 98%) by dermal exposure than the oral in both adults and children. The total ILCR is found to be greater than a low safety risk of 1-in-10,000 with higher probability percentages (>90%). The 95th percentile values of the risk were presented in order to address the need for remediation. Appropriate remedial and treatment methods for the subject site were proposed. The results of the study will be useful for the regulatory boards and policy makers in India in understanding the actual impact of the contamination on receptors, setting up final remediation goals and deciding on a specific remedial method. PMID- 28985598 TI - Preparation of highly stable zeolite-alginate foam composite for strontium(90Sr) removal from seawater and evaluation of Sr adsorption performance. AB - Alginate bead is a promising strontium (Sr) adsorbent in seawater, but highly concentrated Na ions caused over-swelling and damaged the hydrogel bead. To improve the mechanical stability of alginate bead, flexible foam-type zeolite alginate composite was synthesized and Sr adsorption performance was evaluated in seawater; 1-10% zeolite immobilized alginate foams were prepared by freeze-dry technique. Immobilization of zeolite into alginate foam converted macro-pores to meso-pores which lead to more compact structure. It resulted in less swollen composite in seawater medium and exhibited highly improved mechanical stability compared with alginate bead. Besides, Sr adsorption efficiency and selectivity were enhanced by immobilization of zeolite in alginate foam due to the increase of Sr binding sites (zeolite). In particular, Sr selectivity against Na was highly improved. The 10% zeolite-alginate foam exhibited a higher log Kd of 3.3, while the pure alginate foam exhibited 2.7 in the presence of 0.1 M Na. Finally, in the real seawater, the 10% zeolite-alginate foam exhibited 1.5 times higher Sr adsorption efficiency than the pure alginate foam. This result reveals that zeolite-alginate foam composite is appropriate material for Sr removal in seawater due to its swelling resistance as well as improved Sr adsorption performance in complex media. PMID- 28985599 TI - Can the skin make you fat? A role for the skin in regulating adipose tissue function and whole-body glucose and lipid homeostasis. AB - Prevalence of obesity and related complications such as type 2 diabetes (T2D) has increased dramatically in recent decades. Metabolic complications of obesity arise in part due to subcutaneous adipose tissue (SAT) dysfunction. However, it is currently unclear why some obese individuals develop insulin resistance and T2D and others do not. In this review, we discuss the role of the skin in regulating SAT function, and whether presence of inflammatory skin diseases such as psoriasis represent a novel risk mechanism mediating development of obesity related complications. PMID- 28985600 TI - Factors affecting the roles of reactive species in the degradation of micropollutants by the UV/chlorine process. AB - The UV/chlorine process is an emerging advanced oxidation process (AOP) that produces various reactive species, such as hydroxyl radicals (HO) and reactive chlorine species (RCS). The effects of the treatment conditions, such as chlorine dosage and pH, and the water matrix components of natural organic matter (NOM), alkalinity, ammonia and halides, on the kinetics and reactive species in the degradation of four micropollutants, metronidazole (MDZ), nalidixic acid (NDA), diethyltoluamide (DEET) and caffeine (CAF), by the UV/chlorine process were investigated. The degradation of MDZ and CAF was primarily attributable to HO and ClO, respectively, while that of NDA was primarily attributable to both ClO and CO3-. HO, Cl and CO3- are important for the degradation of DEET. The second-order rate constants for ClO with CAF and CO3- with NDA were determined to be 5.1 (+/ 0.2) * 107 M-1s-1 and 1.4 (+/-0.1) * 107 M-1s-1, respectively. Increasing chlorine dosage slightly changed the contribution of HO but linearly increased that of ClO to micropollutant degradation. Increasing pH decreased the contribution of either HO or Cl but not that of ClO. Both NOM and bicarbonate decreased the contributions of HO and Cl, whereas NOM but not bicarbonate significantly decreased that of ClO. The contribution of either HO or Cl first rose and then fell as the molar ratio of ammonia to chlorine increased from 0 to 1:1, while that of ClO decreased. The co-presence of high concentrations of Cl- and Br- enhanced the contribution of ClBr- and BrCl. PMID- 28985601 TI - A risk-based approach for developing standards for irrigation with reclaimed water. AB - A generalised quantitative risk assessment (QRA) is developed to assess the potential harm to human health resulting from irrigation with reclaimed water. The QRA is conducted as a backward calculation starting from a pre-defined acceptable risk level at the receptor point (defined as an annual infection risk of 10-4 for pathogens and by reference doses (RfD) for chemical hazards) and results in an estimate of the corresponding acceptable concentration levels of the given hazards in the effluent. In this way the QRA is designed to inform the level of water treatment required to achieve an acceptable risk level and help establish reclaimed water quality standards. The QRA considers the exposure of human receptors to microbial and chemical hazards in the effluent through various exposure pathways and routes depending on the specific irrigation scenario. By considering multiple pathways and routes, a number of key aspects relevant to estimating human exposure to recycled water can be accounted for, including irrigation and crop handling practices (e.g., non-edible vs edible, spray vs. drip, withholding time) and volumes consumed (directly vs indirectly). The QRA relies on a large number of inputs, many of which were found to be highly uncertain. A possibilistic approach, based on fuzzy set theory, was used to propagate the uncertain input values through the QRA model to estimate the possible range of hazard concentrations that are deemed acceptable/safe for reclaimed water irrigation. Two scenarios were considered: amenity irrigation and irrigation of ready-to-eat food crops, and calculations were carried out for six example hazards (norovirus, Cryptosporidium, cadmium, lead, PCB118 and naphthalene) and using UK-specific input values. The human health risks associated with using reclaimed water for amenity irrigation were overall deemed low, i.e. the calculated acceptable concentration levels for most of the selected hazards were generally far greater than levels typically measured in effluent from wastewater treatment plants; however the predicted acceptable concentration levels for norovirus and Cryptosporidium suggested that disinfection by UV may be required before use. It was found that stricter concentration standards were required for hazards that are more strongly bound to soil and/or are more toxic/infectious. It was also found that measures that reduce the amount of effluent directly ingested by the receptor would significantly reduce the risks (by up to 2 orders of magnitude for the two pathogens). The results for the food crop irrigation scenario showed that stricter concentration standards are required to ensure the effluent is safe to use. For pathogens, the dominant exposure route was found to be ingestion of effluent captured on the surface of the crops indicating that risks could be significantly reduced by restricting irrigation to the non-edible parts of the crop. The results also showed that the exposure to some organic compounds and heavy metals through plant uptake and attached soil particles could be high and possibly pose unacceptable risk to human health. For both scenarios, we show that the predicted acceptable concentration levels are associated with large uncertainty and discuss the implications this has for defining quality standards and how the uncertainty can be reduced. PMID- 28985602 TI - Experiences of women receiving childbirth care from public health facilities in Kumasi, Ghana. AB - OBJECTIVE: to explore women's experiences with childbirth care in Kumasi, Ghana. DESIGN: exploratory, qualitative research design using in-depth interviews and content analysis. SETTING: four public health facilities in Kumasi, Ghana. PARTICIPANTS: fifty-six women attending either antenatal or postnatal care at the four public health facilities. MEASUREMENTS AND FINDINGS: individual in-depth interviews were used to explore women's experiences with childbirth care. Mothers had both encouraging and discouraging experiences during care, which influenced their willingness to seek assisted health care during childbirth in the future. Participants who had experiences of empathetic support and continuous labour support and attention reported these to be encouraging. Other participants reported discouraging experiences such as disrespectful care and inadequate communication and involvement in care decisions. KEY CONCLUSIONS: Women in our study wanted to be seen as partners in the care process and not subordinate to care providers. IMPLICATIONS FOR PRACTICE: Midwives and student midwives must be given the tools and support to deliver patient-centred childbirth care. PMID- 28985603 TI - Immobilization of Candida antarctic lipase B on MWNTs modified by ionic liquids with different functional groups. AB - Multiwalled carbon nanotubes (MWNTs) were modified by imidazole-based ionic liquids with different kinds of functional groups such as alkyl, carboxyl, amino and hydroxyl. The supports were used to immobilize Candida antarctic lipase B (CALB) and the influence of different functional groups of ionic liquids on enzymatic properties was investigated by the hydrolysis reaction of triacetin. The results revealed that the functionalization process did not destroy the structural integrity of MWNTs, and the enzymatic properities of CALB which immobilized on the MWNTs modified by ionic liquids with different kinds of functional groups were all improved. The hydroxyl functionalized ionic liquids which exhibited the best enzymatic properities was selected to investigate the effects of different carbon chain length on the enzymatic properties of immobilized CALB. Among them, CALB which immobilized on MWNTs modified by hydroxyl functionalized ionic liquid with suitable chain length (MWNTs-IL(8C)-OH CALB) had the highest specific activity, with a specific activity of 18.11 times that of MWNTs-CALB. Furthermore, it also presented best thermal stability and reusability. The residual activity of MWNTs-IL(8C)-OH-CALB held over 64.01% of the initial activity after being incubated for 20min at 70 degrees C, and the residual activity was 85.56% after 4 cycles of use. PMID- 28985604 TI - Gold nanoflowers synthesized using Acanthopanacis cortex extract inhibit inflammatory mediators in LPS-induced RAW264.7 macrophages via NF-kappaB and AP-1 pathways. AB - We reported the rapid synthesis (<8s) of gold nanoparticles at room temperature using Acanthopanacis cortex extract (A-AuNPs). We characterized the A-AuNPs using several analytical techniques and found that nano-flower type A-AuNPs, which are known to possess a coarse surface with a high surface to volume ratio, conferring these particles with high binding capacity for various biological molecules. After confirming the stability of the nanoparticles, we investigated the anti inflammatory effect of A-AuNPs in LPS-stimulated RAW264.7 cells. These nanoparticles inhibited LPS-induced iNOS and COX-2 protein as well as gene expression level, along with reduction of NO and PGE2 production. Furthermore, we observed that the A-AuNPs inhibited translocation of NF-kappaB and AP-1 through phosphorylation of MAPK signaling by western blot analysis. In summary, we synthesized gold nanoflowers in an economical and eco-friendly way using Acanthopanacis cortex extract and the resultant flower-like A-AuNPs had anti inflammatory activity, highlighting their potential as therapeutic candidates for suppression of inflammatory-mediated diseases. PMID- 28985605 TI - Adsorption and covalent binding of fibrinogen as a method for probing the chemical composition of poly(styrene/alpha-tert-butoxy-omega-vinylbenzyl polyglycidol) microsphere surfaces. AB - We investigated the distribution of polyglycidol and polystyrene on the surface of poly(styrene/alpha-tert-butoxy-omega-vinylbenzyl-polyglycidol) microspheres (random distribution or segregated into hydrophilic and hydrophobic patches), using fibrinogen (Fb) as a macromolecular probe. The fibrinogen was adsorbed or covalently attached to the surface of the poly(styrene-co-alpha-tert-butoxy-omega vinylbenzyl-polyglycidol) (P(S/PGLy)) microspheres. The P(S/PGLy) particles were prepared by emulsion copolymerization of styrene and alpha-tert-butoxy-omega vinylbenzyl-polyglycidol (PGLy) macromonomer initiated with potassium persulfate. The polymerizations yielded P(S/PGLy) particles with various surface fractions of polyglycidol, depending on the amount of added macromonomer and the addition process. In some syntheses, the entire macromonomer amount was added once at the beginning of the polymerization, while in others, the macromonomer was added gradually after the formation of particle seeds from pure polystyrene. XPS studies revealed that the fraction of polyglycidol in the interfacial layer of the microspheres was larger when the entire amount of macromonomer was added at the beginning of the polymerization than when it was added after formation of the polystyrene seeds. Studies of fibrinogen adsorption provided the first evidence of segregation of the hydrophobic (polystyrene) and hydrophilic (polyglycidol) components at the surface of the composite P(S/PGLy) microspheres into patches. The hydrophobic patches are composed mainly of polystyrene. However, they also contain a small amount of polyglycidol chains, making the adsorption of fibrinogen weaker than the adsorption onto the pure polystyrene. Studies of covalent immobilization of fibrinogen on the microspheres via 1,3,5 trichlorotriazine confirmed these findings. PMID- 28985606 TI - Preparation of artificial red cell and its application on alleviation of tumor hypoxia. AB - Hemoglobin-based oxygen carriers were developed as an alternative for blood transfusion. However, the research progress for their further clinic applications was slow in recent several years. Hypoxia is found in most solid tumors, which is responsible for the tumor formation, increased metastasis, drug resistance during therapeutic process as well as poor patient survival. In this work, novel hemoglobin (Hb) loaded nanoliposomes, as artificial red cells for oxygen delivery, were optimized by screening various types of phospholipids and analyzing different mole ratio of phospholipid to cholesterol. The nanoliposomes presented a high encapsulating efficiency to hemoglobin and also significantly enhanced its stability. The obtained hemoglobin loaded nanoliposome (HLL) could be lyophilized for long term storage. HLL did not cause significant cell death in the concentration range of 0-100MUg equivalent Hb/mL under normoxia and hypoxia incubation conditions, suggesting the low cytotoxicity and high biocompatibility of HLL. Importantly, HLL could efficiently accumulate into subcutaneous and deep orthotopic tumors, inducing a significant decrease of hypoxia-inducible factors 1alpha subunits (HIF-1alpha) in the tumors and remarkably reduced expression of vascular endothelial growth factor (VEGF). The study of acute and chronic toxicity indicated that HLL did not induce obvious damage to main organs of mice after intravenous injections with total Hb dose of 120mg/kg. We presented a promising method for relieving the hypoxia degree in solid tumors and down regulating HIF-1alpha protein by directly delivering oxygen into tumors, which will be very helpful for subsequent cancer therapy. PMID- 28985607 TI - Design of pH/reduction dual-responsive nanoparticles as drug delivery system for DOX: Modulating controlled release behavior with bimodal drug-loading. AB - pH/Reduction dual-responsive P(FPA-co-PEGMA-co-MAA) (PFPM) nanoparticles were designed for tumor-specific intracellular triggered release of anticancer drug DOX by emulsion copolymerization of 4-formylphenyl acrylate (FPA), methacrylic acid (MAA), and poly(ethylene glycol) methyl ether methacrylate (PEGMA), with N,N bis(acryloyl)cystamine (BACy) as crosslinker. Then three drug delivery systems (DDSs) with average hydrodynamic diameter around 200nm and drug-loading capacity (DLC) of >35% were obtained via the noncovalent interaction of DOX with the carboxyl and aldehyde groups in MAA and FPA units, covalently conjugating DOX onto the FPA units via acid-labile imine bond, or both the two modes. The in vitro release profiles showed that all the three DDSs exhibited good tumor intracellular triggered release characteristic whitout burst release. And the bimodal drug-loaded one (DOX/PFPMC+N), which had the highest DLC of >54%, possessed the middle drug release rate, faster than the one via covalent conjugation (DOX/PFPMC) but slower than the one via noncovalent interaction (DOX/PFPMN). The results demonstrated that the controlled release behavior of such functional nanoparticles could be tailored with drug-loading modes. PMID- 28985609 TI - Inhibition of autophagy modulates astaxanthin and total fatty acid biosynthesis in Chlorella zofingiensis under nitrogen starvation. AB - The present study showed that inhibition of autophagy significantly increased cellular levels of reactive oxygen species in Chlorella zofingiensis under nitrogen starvation. This was accompanied with increased expression of PSY, and enhanced accumulation of astaxanthin after 48h of cultivation. Nevertheless, the proportion of astaxanthin in secondary carotenoids remained unchanged. Meanwhile, the expression level of ACCase was also elevated in the 3-MA-treated cells compared to the control despite a >20% lower content of fatty acid in the former than the latter. This phenomenon might be due to inhibition of recycling of cellular components by 3-MA and suggests the potential involvement of post transcriptional regulation in fatty acid biosynthesis. In summary, our work has been the first to report a potentially important role of autophagy in fatty acid and astaxanthin accumulation in C. zofingiensis under stress conditions. The findings might provide valuable insights to guide further research in this area. PMID- 28985608 TI - The role of neutrophil gelatinase-associated lipocalin (NGAL) in the detection of blast lung injury in a military population. AB - PURPOSE: To study the relationship between serum neutrophil gelatinase-associated lipocalin (NGAL) and military blast and gunshot wound (GSW) to establish whether potential exists for NGAL as a biomarker for blast lung injury (BLI). METHOD: Patients from the intensive care unit (ICU) of the Role 3 Medical Treatment Facility at Camp Bastion, Helmand Province, Afghanistan were studied over a five month period commencing in 2012. Age, mechanism, trauma injury severity score (TRISS) and serum NGAL were recorded on ICU admission (NGAL1). Serum NGAL (NGAL2) and PaO2/FiO2 ratio (P/F ratio2) were recorded at 24h. RESULTS: 33 patients were injured by blast and 23 by GSW. NGAL1 inversely correlated with TRISS (p=0.020), pH (p=0.002) and P/F ratio 2 (p=0.009) overall. When data was stratified into blast and GSW, NGAL1 also inversely correlated with P/F ratio 2 in the blast injured group (p=0.008) but not GSW group (p=0.27). CONCLUSION: Raised NGAL correlated with increased severity of injury (worse survival probability i.e. TRISS and low pH) in both patient groups. There was an inverse correlation between admission NGAL and a marker of blast lung injury (low P/F ratio) at 24h in blast injured group but not GSW group that warrants further investigation. PMID- 28985610 TI - Acclimation to extremely high ammonia levels in continuous biomethanation process and the associated microbial community dynamics. AB - Acclimatized anaerobic communities to high ammonia levels can offer a solution to the ammonia toxicity problem in biogas reactors. In the current study, a stepwise acclimation strategy up to 10g NH4+-N L-1, was performed in mesophilic (37+/-1 degrees C) continuously stirred tank reactors. The reactors were co-digesting (20/80 based on volatile solid) cattle slurry and microalgae, a protein-rich, 3rd generation biomass. Throughout the acclimation period, methane production was stable with more than 95% of the uninhibited yield. Next generation 16S rRNA gene sequencing revealed a dramatic microbiome change throughout the ammonia acclimation process. Clostridium ultunense, a syntrophic acetate oxidizing bacteria, increased significantly alongside with hydrogenotrophic methanogen Methanoculleus spp., indicating strong hydrogenotrophic methanogenic activity at extreme ammonia levels (>7g NH4+-N L-1). Overall, this study demonstrated for the first time that acclimation of methanogenic communities to extreme ammonia levels in continuous AD process is possible, by developing a specialised acclimation AD microbiome. PMID- 28985611 TI - Photo and biocatalytic activities along with UV protection properties on polyester fabric through green in-situ synthesis of cauliflower-like CuO nanoparticles. AB - In this paper, a facile environmentally friendly method is introduced for in-situ synthesis and fabrication of cauliflower-like CuO nanoparticles on the polyester fabric to produce photo and biocatalytic activities with UV protection properties on polyester fabric. The ash of burnt leaves and stems of Seidlitzia rosmarinus plant called Keliab was used as a natural and nontoxic alkaline source for simultaneous synthesis of CuO nanoparticles and surface modification of polyester without using any other compounds. The images of field-emission scanning electron microscopy, patterns of energy-dispersive spectroscopy, UV-visible spectrum and X ray diffraction confirmed successful synthesis and loading of CuO nanoparticles on the polyester fabric. The treated fabrics showed very good antibacterial activities toward two pathogen bacteria including Staphylococcus aureus as a Gram positive and Escherichia coli as a Gram-negative bacteria with no adverse effects on human dermal fibroblasts based on MTT test. The treated fabrics confirmed significant photocatalytic activity for degradation of methylene blue under sunlight, self-cleaning properties under UV light and also UV protection properties. Further a colorant effect along with an improvement in the wettability and mechanical properties of the treated fabrics were indicated. Overall, this method can be applied as a clean route for producing photo and bio active textiles protecting against UV irradiation. PMID- 28985612 TI - A dual marker label free electrochemical assay for Flavivirus dengue diagnosis. AB - Dengue is a RNA viral illness of the genus Flavivirus which can cause, depending on the pervasiveness of the infection, hemorrhagic dengue fever or dengue shock syndrome. Herein we present an electrochemical label free approach enabling the rapid sensitive quantification of NS1 and IgG (supporting an ability to distinguish primary and secondary infections). Using a bifunctional SAM containing PEG moieties and a tethered redox thiol, both markers are detectable across clinically relevant levels by label free impedance derived redox capacitance. A subsequent frequency specific immittance function approach enables assaying (within seconds) with no impairment of analytical quality (linearity, sensitivity and variance). PMID- 28985613 TI - Preventable complications in epilepsy admissions: The "July effect". AB - BACKGROUND: Inpatient hospital stays for patients with epilepsy represent a significant burden on patients and society. Identifying factors that contribute to such costs aides in developing effective strategies to address this burden. July admissions have been associated with higher rates of complications and worse outcomes, attributed to the presence of new physicians. This study aims to evaluate whether epilepsy patients admitted in July have higher preventable complication rates and mortality than during the rest of the year. METHODS: Data was derived from the Nationwide Inpatient Sample (NIS) for epilepsy admissions for the years 2000-2010. Multivariable analyses assessed the effect of July against non-July admission on "hospital acquired complications" (HAC), which are complications identified as owing to preventable causes and mortality. Additionally, the total adjusted charges and prolonged length of stay (pLOS) for July admissions were compared to the 50th percentile. RESULTS: A total of 12,997,181 admissions for epilepsy were identified with 993,619 (8%) occurring in July, 10,810,900 (83%) were non-July months, and 1,192,662 (9%) were missing data. Patients admitted in July showed an increased association for HAC events (RR=1.02, [1.01,1.03], p<0.01), but a decrease in mortality (RR=0.96, [0.95,0.97], p<0.01). There was no difference in rates of higher total adjusted charges for July admissions (RR=1.00, [1.00,1.00], p<0.01) and a decrease in rates of pLOS (RR=0.99, [0.98,0.99], p<0.01). CONCLUSION: In the epilepsy population, although July admissions were associated with a slight increase in HAC events, there was a non-significant or decreased rate of mortality, LOS, and total charge. Our results suggest that although complications were increased in July, possibly due to new staff, supervision is sufficient to prevent significant burden on patients and hospitals. PMID- 28985614 TI - Complement system dysregulation in patients affected by Idiopathic Generalized Epilepsy and the effect of antiepileptic treatment. AB - Complement system dysregulation has been hypothesized as a possible pathogenetic factor triggering epileptogenesis in both animal models and human studies. The aim of the present study is to evaluate the complement system in adult patients affected by idiopathic generalized epilepsy (IGE), either untreated or treated by antiepileptic drugs (AEDs). Thirty-seven IGE patients were compared to a population of 20 matched healthy controls. IGE patients underwent neurological investigation, epilepsy diary, 24-h EEG recording, and blood sample for the assessment of the complement factors C3 and C4, fibrinogen, and C-reactive protein (CRP) serum levels. We excluded patients with clinical and subclinical seizures in the 24h before obtaining the blood sample. We observed decreased C3 and C4 serum levels in IGE patients with respect to controls (p<0.05), and in untreated compared to treated IGE patients (p<0.05). We found significant correlations in the IGE group linking C3 to C4 (R=0.34), CRP (R=0.49), and fibrinogen serum levels (R=0.61). This study proved a significant alteration of the complement system in IGE patients not related to ictal conditions. The hyperactivation of the complement cascade was more significant in untreated than in treated IGE patients. Hence, this study documented the complement factors dysregulation in patients affected by IGE. However, the impact of complement system alteration in the epileptogenetic process needs to be clarified. PMID- 28985615 TI - Body temperature and motion: Evaluation of an online monitoring system in pigs challenged with Porcine Reproductive & Respiratory Syndrome Virus. AB - Highly contagious and emerging diseases cause significant losses in the pig producing industry worldwide. Rapid and exact acquisition of real-time data, like body temperature and animal movement from the production facilities would enable early disease detection and facilitate adequate response. In this study, carried out within the European Union research project RAPIDIA FIELD, we tested an online monitoring system on pigs experimentally infected with the East European subtype 3 Porcine Reproductive & Respiratory Syndrome Virus (PRRSV) strain Lena. We linked data from different body temperature measurement methods and the real-time movement of the pigs. The results showed a negative correlation between body temperature and movement of the animals. The correlation was similar with both body temperature obtaining methods, rectal and thermal sensing microchip, suggesting some advantages of body temperature measurement with transponders compared with invasive and laborious rectal measuring. We also found a significant difference between motion values before and after the challenge with a virulent PRRSV strain. The decrease in motion values was noticeable before any clinical sign was recorded. Based on our results the online monitoring system could represent a practical tool in registering early warning signs of health status alterations, both in experimental and commercial production settings. PMID- 28985616 TI - Bio-corrosion behavior and mechanical characteristics of magnesium-titania hydroxyapatite nanocomposites coated by magnesium-oxide flakes and silicon for use as resorbable bone fixation material. AB - This study was aimed to improve of the corrosion resistance and mechanical properties of Mg/15TiO2/5HA nanocomposite by silicon and magnesium oxide coatings prepared using a powder metallurgy method. The phase evolution, chemical composition, microstructure and mechanical properties of uncoated and coated samples were characterized. Electrochemical and immersion tests used to investigate the in vitro corrosion behavior of the fabricated samples. The adhesion strength of ~36MPa for MgO and ~32MPa for Si/MgO coatings to substrate was measured by adhesion test. Fabrication a homogenous double layer coating with uniform thicknesses consisting micro-sized particles of Si as outer layer and flake-like particles of MgO as the inner layer on the surface of Mg/15TiO2/5HA nanocomposite caused the corrosion resistance and ductility increased whereas the ultimate compressive stress decreased. However, after immersion in SBF solution, Si/MgO-coated sample indicates the best mechanical properties compared to those of the uncoated and MgO-coated samples. The increase of cell viability percentage of the normal human osteoblast (NHOst) cells indicates the improvement in biocompatibility of Mg/15TiO2/5HA nanocomposite by Si/MgO coating. PMID- 28985617 TI - The alpha-lipoic acid improves high-fat diet-induced cerebral damage through inhibition of oxidative stress and inflammatory reaction. AB - This study is to clarify the protective role of alpha-lipoic acid in high-fat diet-induced cerebral damage mice. The mice were divided into 5 groups: normal control group, high-fat diet (HFD) group, low-dose alpha-lipoic acid group for prevention, high-dose alpha-lipoic acid group for prevention, and high-dose alpha lipoic acid group for treatment. The groups' weights and blood glucose changes were monitored. We used HE staining to observe morphological changes in the cerebral cortex. The expression levels of the oxidative stress proteins SOD2, catalase, and the inflammatory pathway proteins p-JNK, p-ERK were measured by western blot and immunochemistry. Compared with the control group, the quantity of cortical neurons in the HFD group was decreased, and the samples exhibited retrogression. However, the lipoic acid significantly protected and promoted the cortical neurons survival. Moreover, compared with the HFD group, the expression levels of SOD2 and catalase in the three alpha-lipoic acid obtained groups were significantly increased. However, the expression levels of the inflammatory pathway proteins p-JNK and p-ERK were significantly decreased. These results indicate that thealpha-lipoic acid greatly protects the cortical neurons, and inhibited the oxidative stress and inflammatory reactions in the high-fat diet mice. PMID- 28985618 TI - Intake of DDT and its metabolites through food items among reproductive age women in Bangladesh. AB - This study was conducted to make clear the major intake route of DDT in Bangladesh people to develop strategy and policy that could lead to a reduction in body burden especially in the reproductive age women. The concentrations of several POPs (DDT, PCBs, chlordanes, HCHs, HCB, and PeCB) were quantified in food items, human breast milk and house dust collected in Bangladesh in 2011-2012. Among the POPs analyzed in this study, DDT and its metabolites (SigmaDDT) showed the highest concentration. The highest median SigmaDDT concentration was found in meat (1.3-1100 ng g-1 wet weight) and house dust (30-1100 ng g-1 dry weight), and followed by human breast milk (20-55 ng g-1 wet weight). Estimated daily intake (EDI) was calculated using the DDT concentrations in food items. The highest intake of DDT was found in an infant and 99% of it was via breast milk feeding. DDT intake via consumption of beef accounted for 69% and 72% of that found in children and adults, respectively. The total EDI of DDT did not exceed the tolerable daily intake proposed by the WHO, but the EDI of p,p'-DDT exceeded the oral reference dose proposed by the US Environmental Protection Agency. Further research is required to clarify the reason for the high levels of DDT in beef, which seems to be the major intake route of DDT for women of reproductive age in Bangladesh. PMID- 28985619 TI - Determination of 20, 25-diazacholesterol in avian matrices by high performance liquid chromatography/tandem mass spectrometry. AB - Wildlife contraceptives are an emerging tool for minimizing human-wildlife conflicts. One promising avian contraceptive compound, 20,25-diazacholesterol (DAC), reduces fertility by inhibiting cholesterol synthesis. A reliable analytical method for DAC was required in support of its registration for use as a reproductive control agent in pest bird species. A liquid chromatographic method employing tandem mass spectrometry (LC-MS/MS) was developed for the analysis of tissue extracts following solid phase extraction clean-up. Tissues analyzed were whole body samples from crows, monk parakeets, and quails and liver samples from crows and quails. Excellent sensitivity and selectivity was afforded by tandem mass spectrometry. The method accuracy of DAC from various tissue samples fortified at parts-per-million (ppm) and parts-per-billion (ppb) concentrations was high (>90%) with excellent precision (<10% relative standard deviation). Lower limits of detection were excellent in all tissues types, ranging from 1 to 11ppb in whole body matrices and 9.9-34ppb in liver matrices. PMID- 28985620 TI - Serum levels of leptin, adiponectin and resistin in patients with ankylosing spondylitis: A systematic review and meta-analysis. AB - OBJECTIVES: Various studies have researched the serum levels of leptin, adiponectin and resistin in patients with ankylosing spondylitis (AS), but the results were inconclusive. The purpose of this study was to systematically evaluate the correlations between serum levels of these adipokines and AS. METHODS: Electronic databases were retrieved to search relevant publications. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by the random-effect model. Cochrane Q test and I2 statistic were used to test heterogeneity. Subgroup analysis and meta-regression were applied to assess possible sources of heterogeneity. RESULTS: A total of sixteen articles were included. Meta-analysis results indicated no statistical differences between AS patients and normal controls in serum leptin and adiponectin levels (leptin, SMD=0.829, 95% CI=-0.116 to 1.774, p=0.085; adiponectin, SMD=0.460, 95% CI=-0.004 to 0.924, p=0.052). However, AS patients had higher serum resistin levels than controls (SMD=1.413, 95% CI=0.294 to 2.531, p=0.013). Subgroup analyses suggested that Asian and African AS patients as well as patients aged <40years had higher serum leptin and resistin levels when compared to controls. Serum adiponectin levels were higher in AS patients compared to controls in subgroup of age >=40, and serum resistin levels in subgroup of BMI >=25. Measurement method was a source of heterogeneity for resistin. Publication bias was not observed and the robustness of study results was confirmed by sensitivity analysis. CONCLUSION: Serum resistin, but not leptin or adiponectin levels may be closely associated with the development of AS. PMID- 28985621 TI - Circulating CD4+CXCR5+ T cells contribute to proinflammatory responses in multiple ways in coronary artery disease. AB - Coronary artery disease (CAD) is a common subtype of cardiovascular disease. The major contributing event is atherosclerosis, which is a progressive inflammatory condition resulting in the thickening of the arterial wall and the formation of atheromatous plaques. Recent evidence suggests that circulating CD4+CXCR5+ T cells can contribute to inflammatory reactions. In this study, the frequency, phenotype, and function of circulating CD4+CXCR5+ T cells in CAD patients were examined. Data showed that circulating CD4+CXCR5+ T cells in CAD patients were enriched with a PD-1+CCR7- subset, which was previously identified as the most potent in B cell help. The CD4+CXCR5+ T cells in CAD patients also secreted significantly higher levels of IFN-gamma, IL-17A, and IL-21 than those from healthy controls. Depleting the PD-1+ population significantly reduced the cytokine secretion. Interestingly, the CD4+CXCR5+PD-1- T cells significantly upregulated PD-1 following anti-CD3/CD28 or SEB stimulation. CD4+CXCR5+ T cells from CAD patients also demonstrated more potent capacity to stimulate B cell inflammation than those from healthy individuals. The phosphorylation of STAT1 and STAT3 were significantly higher in B cells incubated with CD4+CXCR5+ T cells from CAD than controls. The IL-6 and IFN-gamma expression were also significantly higher in B cells incubated with CD4+CXCR5+ T cells from CAD. Together, this study demonstrated that CAD patients presented a highly activated CD4+CXCR5+ T cell subset that could contribute to proinflammatory responses in multiple ways. The possibility of using CD4+CXCR5+ T cells as a therapeutic target should therefore be examined in CAD patients. PMID- 28985622 TI - Outcomes and changes in code status of patients with acute myeloid leukemia undergoing induction chemotherapy who were transferred to the intensive care unit. AB - Patients with Acute Myeloid Leukemia (AML) have compromised marrow function and chemotherapy causes further suppression. As a result complications are frequent, and patients may require admission to the intensive care unit (ICU). How codes status changes when these events occur and how those changes influence outcome are largely unknown. Outcomes for adult patients with AML, undergoing induction chemotherapy, and transferred to the ICU between January 2000 and December 2013 were analyzed. 94 patients were included. Median survival was 1.3 months. At 3 and 6 months overall survival (OS) was 27% and 18% respectively. Respiratory failure was the most common reason for transfer to ICU (88%), with 63% requiring mechanical ventilation at transfer. Other reasons included: cardiac arrest (18%), septic shock (17%), hypotension (9%), and acute renal failure (9%). The most frequent interventions were mechanical ventilation in 85%, vasopressors in 62%, and hemodialysis in 30%. Following transfer 55 patients (58%) had a change in code status. Overall, 46 patients (49%) changed from Full Code (FC) to Comfort Care (CC), 7 (7%) from FC to Do Not Resuscitate (DNR), and 2 (2%) from DNR to CC. For the entire cohort, ICU mortality (IM) was 61% and hospital mortality (HM) was 71%. For FC or DNR patients, IM was 30% and HM was 41%. For CC patients, IM was 90% and HM was 100%. Overall, 27 patients (29%) survived to discharge. Of those discharged, 22 (81%) were alive at 3 months and 17 (63%) were alive at 6 months. In conclusion, patients that required ICU admission during induction chemotherapy have a poor prognosis. Code status changed during the ICU stay for the majority of patients and always to a less aggressive status. PMID- 28985623 TI - Maintenance of cellular respiration indicates drug resistance in acute myeloid leukemia. AB - Primary resistance to induction therapy is an unsolved clinical problem in acute myeloid leukemia (AML). Here we investigated drug resistance in AML at the level of cellular metabolism in order to identify early predictors of therapeutic response. Using extracellular flux analysis, we compared metabolic drug responses in AML cell lines sensitive or resistant to cytarabine or sorafenib after 24h of drug treatment to a small cell lung cancer (SCLC) cell line exposed to etoposide. Only drug-resistant AML cells maintained oxidative metabolism upon drug exposure while SCLC cells displayed an overall metabolic shift towards glycolysis, i.e. a Warburg effect to escape drug toxicity. Moreover, primary AML blasts displayed very low glycolytic activity, while oxygen consumption was readily detectable, indicating an essential role of oxidative pathways in the bioenergetics of AML blasts. In line with these observations, analysis of the mitochondrial membrane potential using tetramethylrhodamine ethyl ester staining and flow cytometry allowed for clear discrimination between drug sensitive and resistant AML cell line clones and primary blasts after 24h of treatment with cytarabine or sorafenib. Our data reveal a distinct metabolic phenotype of resistant AML cells and suggest that disrupting oxidative metabolism rather than glycolysis may enhance the cytotoxic effects of chemotherapy in AML. PMID- 28985624 TI - Modal analysis and nonlinear characterization of an airborne power ultrasonic transducer with rectangular plate radiator. AB - Some industrial processes like particle agglomeration or food dehydration among others can be enhanced by the use of power ultrasonic technologies. These technologies are based on an airborne power ultrasonic transducer (APUT) constituted by a pre-stressed Langevin-type transducer, a mechanical amplifier and an extensive plate radiator. In order to produce the desired effects in industrial processing, the transducer has to vibrate in an extensional mode driving an extensive radiator in the desired flexural mode with high amplitude displacements. Due to the generation of these high amplitude displacements in the radiator surfaces, non-linear effects like frequency shifts, hysteresis or modal interactions, among others, may be produced in the transducer behavior. When any nonlinear effect appears, when applying power, the stability and efficiency of this ultrasonic technology decreases, and the transducer may be damaged depending on the excitation power level and the nature of the nonlinearity. In this paper, an APUT with flat rectangular radiator is presented, as the active part of an innovative system with stepped reflectors. The nonlinear behavior of the APUT has been characterized numerically and experimentally in case of the modal analysis and experimentally in the case of dynamic analysis. According to the results obtained after the experiments, no modal interactions are expected, nor do other nonlinear effects. PMID- 28985625 TI - Atomic-scale structure relaxation, chemistry and charge distribution of dislocation cores in SrTiO3. AB - By using the state-of-the-art microscopy and spectroscopy in aberration-corrected scanning transmission electron microscopes, we determine the atomic arrangements, occupancy, elemental distribution, and the electronic structures of dislocation cores in the 10 degrees tilted SrTiO3 bicrystal. We identify that there are two different types of oxygen deficient dislocation cores, i.e., the SrO plane terminated Sr0.82Ti0.85O3-x (Ti3.67+, 0.48 <= x <= 0.91) and TiO2 plane terminated Sr0.63Ti0.90O3-y (Ti3.60+, 0.57 <= y <= 1). They have the same Burgers vector of a[100] but different atomic arrangements and chemical properties. Besides the oxygen vacancies, Sr vacancies and rocksalt-like titanium oxide reconstruction are also identified in the dislocation core with TiO2 plane termination. Our atomic-scale study reveals the true atomic structures and chemistry of individual dislocation cores, providing useful insights into understanding the properties of dislocations and grain boundaries. PMID- 28985626 TI - Criteria and considerations for preparing atom-probe tomography specimens of nanomaterials utilizing an encapsulation methodology. AB - Atom-probe tomography (APT) is a powerful method for characterization of nanomaterials due to its atomic-ppm level detection limit and Angstrom spatial resolution. Sample preparation for nanomaterials is, however, challenging because of their small dimensions and complicated geometries. Nanowires, with their high geometrical aspect ratio and nanowire length, 10 to 100 times their typical diameters, are highly suitable specimens for APT analyses, which can be transferred to silicon microposts using a nanomanipulator for direct APT measurements. This method is, however, prone to poor alignment and a limited field-of-view (FOV). Most importantly, direct implementation of APT with high aspect ratio nanowires may yield a low success rate of ~30%, due to the high electric fields (10-40 V nm-1) associated with APT. While this is acceptable for samples analyzed solely by APT, a low sample yield makes it challenging to perform correlative experiments on the same nanowire specimen, utilizing other sophisticated characterization instruments. Herein, we introduce a general strategy for preparing high-yield APT specimens by encapsulating the nanowires utilizing a conformal atomic-layer deposition (ALD) coating followed by site specific lift-out using a dual-beam focused-ion beam microscope. The ALD deposited coating forms strong chemical bonds with the Si nanowires yielding a high-quality and robust interface. The evaporation electric fields of the ALD coating and the nanowires are tuned by changing laser energy to obtain a uniform evaporation rate. The strong adhesion of the ALD-coating/nanowire interface and uniform evaporation rate produce a >90% specimen yield, with small concentration of reconstruction artifacts in 3-D. Simultaneously, the field-of-view is enhanced and the surface of the nanowire becomes visible, which makes the study of surface adsorption, segregation and oxidation possible. We utilized ALD-ZnO coated silicon nanowires as an example for investigating the criteria for choosing coating materials, laser pulse energy, laser direction, sample geometry, and substrate materials. The same criteria and considerations are applicable for preparing specimens of nanoparticles and 2-D material. PMID- 28985627 TI - Anaeramoebidae fam. nov., a Novel Lineage of Anaerobic Amoebae and Amoeboflagellates of Uncertain Phylogenetic Position. AB - We report discovery of a new lineage of anaerobic marine amoebae and amoeboflagellates, Anaeramoeba gen. nov., represented by six newly described species. The trophic form of Anaeramoeba spp. is an amoeba corresponding to the uncommon flabellate or flamellian morphotype - it is fan-shaped and produces an anterior, flattened hyaline zone and posterior hyaline projections. In contrast to other representatives of these morphotypes, cells of Anaeramoeba spp. possess acristate mitochondrion-related organelles associated with prokaryotic symbionts, and a large acentriolar centrosome. Surprisingly, two Anaeramoeba species form morphologically unique flagellates with two or four isokont, thickened flagella. Phylogenetic analyses of the SSU rRNA gene showed that Anaeramoeba spp. form a clade, which is not robustly related to any other eukaryotic lineage. We accommodate Anaeramoeba in a new family Anaeramoebidae, which we classify as Eukaryota incertae sedis. PMID- 28985628 TI - A mentalization-based approach to common factors in the treatment of borderline personality disorder. AB - In this paper we conceptualize borderline personality disorder as a disorder of mentalizing, social cognition, and loss of resilience. Several treatment approaches are effective, and meta-analyses suggest that there are few substantive differences in effectiveness between them and between specialized and non-specialized approaches. We propose that these findings arise because of shared mechanisms of change, congruent with current thinking both about the existence of a general 'p' factor of psychopathology and a reconceptualization of personality disorders as involving a lack of resilience resulting from problems with epistemic trust and salutogenesis, the capacity to derive benefit from the social environment. Effective treatments share the characteristics of consistency, coherence and continuity, qualities particularly relevant to borderline personality disorder. They create the conditions for the reopening of epistemic trust, an essential component in therapeutic change, as it enables the individual to use the experience of being mentalized, to learn mentalizing of others, and then apply and develop these experiences in day-to-day life, which is the basis for meaningful therapeutic change. PMID- 28985629 TI - DSM-5 alternative model of personality disorder: testing the trait perspective captured in Criterion B. AB - We review the trait model (i.e., Criterion B) included as a central piece of the alternative model of personality disorder (PD) included in DSM-5. The pathological traits are organized into five domains with 25 facets that overlap substantially with basic personality models (e.g., five-factor model). These PD traits can be reliably assessed using a variety of measures; however, questions of poor discriminant validity have been raised. Concerns were raised that this model would result in the loss of clinically meaningful constructs (e.g., borderline personality disorder) but the empirical literature suggests that the traits can faithfully and adequately assess traditional PD constructs. Although personality dysfunction and pathological traits are required for this alternative model, impairment and traits largely overlap with only the latter demonstrating substantial and consistent incremental validity. PMID- 28985630 TI - Impact of preprocedure simethicone on adenoma detection rate during colonoscopy: a multicenter, endoscopist-blinded randomized controlled trial. AB - BACKGROUND AND STUDY AIMS: Ideal bowel preparation for colonoscopy requires complete removal of fluid and foam from the colon. Polyethylene glycol (PEG) is widely used for bowel preparation, with antifoaming agents such as simethicone commonly used in combination with PEG. Data on the effect of simethicone on the adenoma detection rate (ADR) were limited. This study therefore aimed to investigate whether preprocedure simethicone could increase the ADR. PATIENTS AND METHODS: This was a prospective, multicenter, endoscopist-blinded randomized controlled trial involving consecutive patients who underwent colonoscopy in six centers in China. Patients were randomly assigned to one of two groups: PEG plus simethicone or PEG alone. The primary outcome was ADR; secondary outcomes were quality of bowel preparation, measured by the Boston bowel preparation scale (BBPS) and bubble scores. RESULTS: 583 patients were included. More adenomas were detected in the PEG plus simethicone group than in the PEG alone group (ADR 21.0 % vs. 14.3 %, P = 0.04; advanced ADR 9.0 % vs. 7.0 %, P = 0.38). The mean number of adenomas detected was 2.20 +/- 1.36 vs. 1.63 +/- 0.89 (P = 0.02). Patients in the PEG plus simethicone group showed better bowel cleansing efficacy: BBPS >= 6 in 88.3 % vs. 75.2 % (P < 0.001) and bubble scores of 1.00 +/- 1.26 vs. 3.98 +/- 2.50 (P < 0.001). Abdominal bloating was reported less frequently in the PEG plus simethicone group (7.8 % vs. 19.7 %, P < 0.001) than in the PEG alone group. CONCLUSION: Combined use of PEG and simethicone is associated with a significantly increased ADR in a Chinese population. PMID- 28985631 TI - Introduction to the Current Concepts in Lower Extremity Reconstruction by the Italian Society for Microsurgery. PMID- 28985632 TI - Limb and Flap Salvage in Gustilo IIIC Injuries Treated by Vascular Repair and Emergency Free Flap Transfer. PMID- 28985633 TI - Role of Negative Pressure Therapy as Damage Control in Soft Tissue Reconstruction for Open Tibial Fractures. AB - The concept of damage control orthopaedics (DCO) is a strategy that focuses on managing orthopaedic injuries in polytrauma patients who are in an unstable physiological state. The concept of DCO is an extension of damage control surgery or damage limitation surgery (DCS/DLS). Recently, it has become clear that certain patients, following extensive soft tissue trauma, could benefit from the idea of DCS. In the management of severe lower extremity trauma with exposed fracture sites, aggressive early wound excision debridement, early internal fixation, and vascularized wound coverage within a few days after trauma were proposed. A negative-pressure dressing can be easily and rapidly applied to obtain a temporary closure between surgical stages. While negative pressure wound therapy (NPWT) has clear indications in the management of chronic wounds, its applications in the acute setting in victims of polytrauma are uneven. We conducted a review of the current clinical literature to evaluate the role of NPWT in this field, which points out that the negative pressure, applied immediately after the first debridement, seems to be an optimal bridge to the final reconstruction up to 7 days. PMID- 28985634 TI - Vascular Grafts and Flow-through Flaps for Microsurgical Lower Extremity Reconstruction. PMID- 28985635 TI - Below Knee Stump Reconstruction with a Foot Fillet Flap. PMID- 28985636 TI - Muscle versus Fasciocutaneous Flap in Lower Limb Reconstruction: Is There a Best Option? PMID- 28985637 TI - Retrospective Analysis in Lower Limb Reconstruction: Propeller Perforator Flaps versus Free Flaps. PMID- 28985638 TI - Achilles Region Soft-Tissue Defects: A Reconstructive Algorithm Based on a Series of 46 Cases. PMID- 28985640 TI - [Prophylactic Appendectomy: Yes or No?] AB - Background At more than 50%, appendicitis is the leading cause of acute intra abdominal disease requiring surgery. In the course of various other operations, prophylactic appendectomy (PA) is frequently performed. Objectives This study examines to what extent PA is justified. Patients and Methods A prospective study was performed in all patients (n = 173) undergoing prophylactic appendectomy in Katharinen Hospital Unna between January 2010 and October 2013. The following variables were analysed: age, gender, type of primary surgery, emergency or elective surgery, complications, lethality, intraoperative and histopathological evaluation of the appendix. In addition, patients were contacted postoperatively with the request to complete a questionnaire. Results Prophylactic appendectomy was carried out without any specific complications. 117 patients (68%) participated in the survey. 15% of these patients had suffered symptoms that could be attributable to irritation of the appendix. With only one exception, all appendectomy specimens revealed pathological findings in the histopathological examination. PA allowed the early diagnosis of 4 adenomas, one neuroendocrine tumour and 6 metastases or manifestations of peritoneal carcinomatosis. Conclusion PA is ethically justifiable, as there are few complications. Moreover, it can help to avoid future appendicitis and allows early detection of malignancies. PMID- 28985641 TI - A Genetic Marker Associated with De Quervain's Tenosynovitis. AB - De Quervain's tenosynovitis is a repetitive strain injury involving synovial inflammation of the tendons of the first extensor compartment of the wrist. It is relatively common in the general population, and is the most common radial-sided tendinopathy seen in athletes. Identifying a genetic marker associated with de Quervain's tenosynovitis could provide a useful tool to help identify those individuals with an increased risk for injury. A genome-wide association screen was performed using publically available data from the Research Program in Genes, Environment and Health (RPGEH) including 4,129 cases and 98,374 controls. rs35360670 on chromosome 8 showed an association with de Quervain's tenosynovitis at genome-wide significance (p=1.9*10-8; OR=1.46; 95% CI=1.38-1.59). This study is the first genome-wide screen for de Quervain's tenosynovitis and provides insights regarding its genetic etiology as well as a DNA marker with the potential to inform athletes and other high-risk individuals about their relative risk for injury. PMID- 28985642 TI - Farrerol Modulates Aorta Gene Expression Profile in Spontaneously Hypertensive Rats. AB - Farrerol, a typical natural flavanone and major active component in Rhododendron dauricum var. ciliatum, has been shown to possess vasoactive ability in vitro. The aim of this study was to investigate its effect on aorta gene expression in spontaneously hypertensive rats. Twelve-week-old male normotensive Wistar Kyoto rats and spontaneously hypertensive rats were treated with orally administered farrerol (50 mg/kg body weight) for 8 wk before they were sacrificed. We found that aorta samples showed 444 upregulated genes in control spontaneously hypertensive rats compared with the control Wistar Kyoto rats. Administration of farrerol in spontaneously hypertensive rats increased the expression of 2329 genes in the aorta compared with the control spontaneously hypertensive rats. Gene expression profiles performed on the aorta revealed that farrerol induced changes in vascular smooth muscle contraction, mitogen-activated protein kinase signaling pathway, regulation of actin cytoskeleton, vascular endothelial growth factor signaling pathway, calcium signaling pathway, and renin angiotensin system. Furthermore, 10 genes involved in the pathway of vascular smooth muscle contraction were verified using real-time polymerase chain reaction technique, and several novel potential target genes for the farrerol treatment of hypertension were identified. The findings of this study lend support to the potential use of farrerol as a novel therapeutic and antihypertensive candidate drug to prevent the development of hypertension. PMID- 28985643 TI - Hyperspectral Imaging and Support Vector Machine: A Powerful Combination to Differentiate Black Cohosh (Actaea racemosa) from Other Cohosh Species. AB - Actaea racemosa (black cohosh) has a history of traditional use in the treatment of general gynecological problems. However, the plant is known to be vulnerable to adulteration with other cohosh species. This study evaluated the use of shortwave infrared hyperspectral imaging (SWIR-HSI) in tandem with chemometric data analysis as a fast alternative method for the discrimination of four cohosh species (Actaea racemosa, Actaea podocarpa, Actaea pachypoda, Actaea cimicifuga) and 36 commercial products labelled as black cohosh. The raw material and commercial products were analyzed using SWIR-HSI and ultra-high-performance liquid chromatography coupled to mass spectrometry (UHPLC-MS) followed by chemometric modeling. From SWIR-HSI data (920 - 2514 nm), the range containing the discriminating information of the four species was identified as 1204 - 1480 nm using Matlab software. After reduction of the data set range, partial least squares discriminant analysis (PLS-DA) and support vector machine discriminant analysis (SVM-DA) models with coefficients of determination (R2 ) of >= 0.8 were created. The novel SVM-DA model showed better predictions and was used to predict the commercial product content. Seven out of 36 commercial products were recognized by the SVM-DA model as being true black cohosh while 29 products indicated adulteration. Analysis of the UHPLC-MS data demonstrated that six commercial products could be authentic black cohosh. This was confirmed using the fragmentation patterns of three black cohosh markers (cimiracemoside C; 12 beta,21-dihydroxycimigenol-3-O-L-arabinoside; and 24-O-acetylhydroshengmanol-3-O beta-D-xylopyranoside). SWIR-HSI in conjunction with chemometric tools (SVM-DA) could identify 80% adulteration of commercial products labelled as black cohosh. PMID- 28985644 TI - Accessory Anteromedial Portal may not Provide Clinically Superior Results Compared with the Anteromedial Portal in Anterior Cruciate Ligament Reconstruction. AB - Techniques using the anteromedial portal (AMP) and accessory anteromedial portal (AAMP) are commonly used in anterior cruciate ligament (ACL) reconstruction. The aim of this study was to investigate the radiological and clinical outcomes of arthroscopic single-bundle ACL reconstruction using the AMP or AAMP technique to drill the femoral tunnel. The records of 157 patients who underwent single-bundle ACL reconstruction using the AMP or AAMP technique between 2011 and 2015 were reviewed. The femoral tunnel clock-face position and femoral tunnel and tibial tunnel anterior-posterior (AP) inclination angles were assessed on axial or AP magnetic resonance images. At last follow-up, the Lachman test and pivot-shift test were used to evaluate AP and rotational stability, respectively. The Lysholm knee scoring scale and the International Knee Documentation Committee (IKDC) form were used to evaluate clinical and functional results. No statistically significant differences were found between the groups in patient age, sex, follow up period, or affected side distribution. The mean femoral tunnel inclination angle was 31.13 +/- 8.06 degrees in the AMP group and 30.17 +/- 9.02 degrees in the AAMP group (p = 0.513). The tibial tunnel inclination angle in the AMP group (16.28 +/- 7.89 degrees) was not different from that in the AAMP group (13.70 +/- 6.08 degrees). No significant differences were observed between the two groups in the Lachman test, pivot-shift test, Lysholm knee scoring scale, or IKDC scores. The AAMP technique was not clinically superior to the AMP technique in ACL reconstruction. This is a retrospective comparative study and its level of evidence is III. PMID- 28985645 TI - Happy Birthday to You, Professor Borst. PMID- 28985646 TI - [Not Available]. PMID- 28985647 TI - [Expert Opinions in Court: Liability of the Expert]. AB - Experts in criminal, civil and, increasingly, in social court cases have to present their expert opinions in court. This should be regarded not only as a burden, even if this may at times appear superfluous to the expert, perhaps because the discussion is mere repetition of the opinion he has already written, or because the questions appear to be biased against the expert. Nonetheless, the expert is always advised to appear calm and objective during the interrogation by judges and parties or participants and their legal representatives, and should not allow himself or herself to be provoked by questioning. Furthermore, it may be necessary to correct the written expert statement in the course of the interrogation, but this can be a sign of a truly competent medical expert. The expert consulted can be held liable for adverse health effects resulting from the interrogation and investigation, as well as for deliberate or grossly faulty reports. PMID- 28985648 TI - [Communication and Networking - Results of the Working Group 8 of the Forum Future Public Health, Berlin 2016]. AB - Steady changes in society present challenges to constructive cooperation between stakeholders in the diverse PH landscape of Germany through individualism, globalisation, medical progress, digitalisation, etc. Working group 8 therefore suggests that the PH community should build new internal structures, in order to be able to respond jointly to external challenges, facilitate networking amongst the actors and speak with one voice, when needed. The suggestion is to establish an office that has the task to organise further meetings, harmonize written joint statements and moderate the dialogue amongst peers. PMID- 28985649 TI - Peripheral Blood Mononuclear Cell Immunophenotyping in Fibrodysplasia Ossificans Progressiva Patients: Evidence for Monocyte DNAM1 Up-regulation. AB - BACKGROUND: Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder caused by sporadic heterozygous mutations in ACVR1 gene which progressively leads to severe heterotopic ossification. FOP is characterized by episodic flare-ups triggered by different factors such as viral infections, tissue injuries, vaccinations, or occurring without a recognizable cause. The sporadic course of the disease, the documented presence of an important inflammatory reaction in early lesions and the partial response to corticosteroids support the idea that the immune system, and in particular the innate component, may play a role in FOP pathogenesis. However, an extensive expression profile of the peripheral blood mononuclear cells (PBMC) of FOP patients has never been done. METHODS: In this study, we carried out a wide PBMC immunophenotyping on a cohort of FOP patients and matching controls by multiparametric analysis of the expression of a panel of 37 markers associated with migration, adhesion, inhibition, activation, and cell death of circulating immune cells. RESULTS: We observed a statistically significant increase of the expression of DNAM1 receptor in patients' monocytes as compared to controls, and little but significant differences in the expression profile of CXCR1 (CD181), CD62L, CXCR4 (CD184), and HLA-DR molecules. CONCLUSIONS: DNAM1 had been previously shown to play a pivotal role in monocyte migration through the endothelial barrier and the increased expression detected in patients' monocytes might suggest a role of this surface receptor during the early phases of FOP flare-ups in which the activation of the immune response is believed to represent a crucial event. (c) 2017 International Clinical Cytometry Society. PMID- 28985651 TI - Reply to "Can STN DBS protect both nigral somata and innervation of the striatum?" PMID- 28985650 TI - Can STN DBS protect both nigral somata and innervation of the striatum? PMID- 28985652 TI - Cadmium remobilization from shoot to grain is related to pH of vascular bundle in rice. AB - The remobilization of cadmium (Cd) from shoots to grain is the key process to determine the Cd accumulation in grain. The apoplastic pH of plants is an important factor and signal in influencing on plant responding to environmental variation and inorganic elements uptake. It is proposed that pH of rice plants responds and influences on Cd remobilization from shoots to grain when rice is exposed to Cd stress. The results of hydroponic experiment showed that: pH of the rice leaf vascular bundles among 3 cultivars was almost increased, pH value of 1 cultivar was slightly increasing when rice plants were treated with Cd. The decrease degree of H+ concentration in leaf vascular bundles was different among cultivars. The cultivar with higher decreasing in H+ concentration, showed higher Cd transfer efficiency from shoots to grain. The H+ concentration of leaf vascular bundles under normal condition was negatively correlated to cadmium accumulation in leaf. Moreover, pH change was related to Cd accumulation in shots and remobilization from shoots to grain. Uncovering the role of pH response is a key component for the understanding Cd uptake and remobilization mechanism for rice production. PMID- 28985653 TI - Response surface methodology modeling to improve degradation of Chlorpyrifos in agriculture runoff using TiO2 solar photocatalytic in a raceway pond reactor. AB - This paper deals with the use of a raceway pond reactor (RPR) as an alternative photoreactor for solar photocatalytic applications. Raceway pond reactors are common low-cost reactors which can treat large volumes of water. The experiments were carried out with TiO2 in the agriculture effluent spiked with Chlorpyrifos (CPF) at circumneutral pH. The Response Surface Methodology (RSM) was used to find the optimum process parameters to maximize CPF oxidation from the mathematical model equations developed in this study using R software. By ANOVA, p-value of lack of fit > 0.05 indicated that, the equation was well-fitted. The theoretical efficiency of CPF removal, under the optimum oxidation conditions with UV solar energy of around 697 +/- 5.33 lux, was 84.01%, which is in close agreement with the mean experimental value (80 +/- 1.42%) confirming that the response model was suitable for the optimization. As far as the authors know, this is the first study of CPF removal using RPR in agriculture runoff at circumneutral pH. PMID- 28985655 TI - The Changing Face of Technologically Integrated Neurosurgery: Today's High-Tech Operating Room. AB - Over the last decade, surgical technology in planning, mapping, optics, robotics, devices, and minimally invasive techniques has changed the face of modern neurosurgery. We explore the current advances in clinical technology across all neurosurgical subspecialties, examine how clinical practice is being shaped by this technology, and suggest what the operating room of tomorrow may look like. PMID- 28985654 TI - Environmental pollution affects molecular and biochemical responses during gonadal maturation of Astyanax fasciatus (Teleostei: Characiformes: Characidae). AB - Endocrine disrupting compounds (EDCs) have the potential to alter fish reproduction at various levels of organization. The aim of this study was to assess the impact of a natural environment with heavily anthropogenic influence on the physiological processes involved in reproduction in the freshwater fish lambari (Astyanax fasciatus) using different biomarkers. Adult males and females were collected in different seasons from two distinct sites in the same watershed: Ponte Nova Reservoir (PN) considered a pristine or small anthropogenic influence reference point; and Billings Reservoir (Bil), subjected to a large anthropogenic impact. Biological indices, such as hepatosomatic index and gonadosomatic index (GSI), gonadal histomorphology, fecundity, and biomarkers such as plasma levels of estradiol (E2) as well as hepatic gene expression of its alfa nuclear receptor (ERalpha), were analyzed. Hepatic vitellogenin (VTG) gene expression was evaluated in both sexes, as an indicator of xenoestrogen exposure. Females collected at PN presented a typical annual variation reflected in GSI, whereas for those sampled at Bil the index did not change through the seasons. The higher concentration of E2 in males collected at Bil during spring/2013, together with the detection of VTG gene expression, suggest the presence of EDCs in the water. These EDCs may have also influenced fecundity of females from Bil, which was higher during winter and spring/2013. Gene expression of ERalpha and ovarian morphology did not differ between fish from both sites. Water conditions from Bil reservoir impacted by anthropic activity clearly interfered mainly with biomarkers of biological effect such as plasma E2 levels and absolute and relative fecundity, but also altered biomarkers of exposure as VTG gene expression. These facts support the notion that waterborne EDCs are capable of causing estrogenic activity in A. fasciatus. PMID- 28985656 TI - Virtual Reality and Simulation in Neurosurgical Training. AB - Recent biotechnological advances, including three-dimensional microscopy and endoscopy, virtual reality, surgical simulation, surgical robotics, and advanced neuroimaging, have continued to mold the surgeon-computer relationship. For developing neurosurgeons, such tools can reduce the learning curve, improve conceptual understanding of complex anatomy, and enhance visuospatial skills. We explore the current and future roles and application of virtual reality and simulation in neurosurgical training. PMID- 28985657 TI - The Orbit as Seen Through Different Surgical Windows: Extensive Anatomosurgical Study. AB - A thorough understanding of the orbit, structures within it, and complex spatial relationships among these structures bears relevance in a variety of neurosurgical cases. We describe the 3-dimensional surgical anatomy of the orbit and fragile and complex network of neurovascular architectures, flanked by a series of muscular and glandular structures, found within the orbital dura. PMID- 28985658 TI - Neurosurgical Odyssey: Case of Anaplastic Meningiomatosis. PMID- 28985659 TI - Letter to the Editor Regarding "Burr-Hole Drainage for Chronic Subdural Hematoma Under Low-Dose Acetylsalicylic Acid: A Comparative Risk Analysis Study". PMID- 28985660 TI - Outcomes and Recurrences After Chronic Subdural Hematoma Evacuation. PMID- 28985661 TI - Surgical Treatment of Significant Asymptomatic Carotid Stenosis: for the Motion. PMID- 28985662 TI - Pharmacy-Mediated Antiplatelet Management Algorithm Surrounding Neurointerventional Stenting and Flow Diversion Procedures. PMID- 28985663 TI - In Reply to the Letter to the Editor "Pharmacy-Mediated Antiplatelet Management Algorithm Surrounding Neurointerventional Stenting and Flow Diversion Procedures". PMID- 28985664 TI - Apples and Oranges: Proper Comparison of Costs - Endonasal vs. Transnasal. PMID- 28985665 TI - In Reply to the Letter to the Editor "Apples and Oranges: Proper Comparison of Costs - Endonasal vs. Transnasal". PMID- 28985666 TI - Letter to the Editor Regarding "The Likelihood of Reaching Substantial Clinical Benefit After an Interlaminar Dynamic Spacer for Chronic Low Back Pain: A Clinical and Radiologic Analysis of a Prospective Cohort". PMID- 28985667 TI - In Reply to the Letter to the Editor Regarding "The Likelihood of Reaching Substantial Clinical Benefit After an Interlaminar Dynamic Spacer for Chronic Low Back Pain: A Clinical and Radiologic Analysis of a Prospective Cohort". PMID- 28985668 TI - From the Annals of Weill Cornell Neurological Surgery. PMID- 28985669 TI - Establishment of Next-Generation Neurosurgery Research and Training Laboratory with Integrated Human Performance Monitoring. AB - Quality of neurosurgical care and patient outcomes are inextricably linked to surgical and technical proficiency and a thorough working knowledge of microsurgical anatomy. Neurosurgical laboratory-based cadaveric training is essential for the development and refinement of technical skills before their use on a living patient. Recent biotechnological advances including 3-dimensional (3D) microscopy and endoscopy, 3D printing, virtual reality, surgical simulation, surgical robotics, and advanced neuroimaging have proved to reduce the learning curve, improve conceptual understanding of complex anatomy, and enhance visuospatial skills in neurosurgical training. Until recently, few means have allowed surgeons to obtain integrated surgical and technological training in an operating room setting. We report on a new model, currently in use at our institution, for technologically integrated surgical training and innovation using a next-generation microneurosurgery skull base laboratory designed to recreate the setting of a working operating room. Each workstation is equipped with a 3D surgical microscope, 3D endoscope, surgical drills, operating table with a Mayfield head holder, and a complete set of microsurgical tools. The laboratory also houses a neuronavigation system, a surgical robotic, a surgical planning system, 3D visualization, virtual reality, and computerized simulation for training of surgical procedures and visuospatial skills. In addition, the laboratory is equipped with neurophysiological monitoring equipment in order to conduct research into human factors in surgery and the respective roles of workload and fatigue on surgeons' performance. PMID- 28985672 TI - Thiol-Stabilized Gold Nanoparticles: New Ways To Displace Thiol Layers Using Yttrium or Lanthanide Chlorides. AB - We use the aurophilic interactions shown by lanthanides to overcome the sulfur gold interaction. UV-vis and X-ray photoelectron spectroscopy confirm that yttrium or lanthanide chlorides easily displace sulfur ligands from the surface of thiol-stabilized gold nanoparticles. PMID- 28985671 TI - Challenges and Opportunities of Nontraditional Approaches to Treating Bacterial Infections. AB - Due to increasing rates of antimicrobial-resistant infections and the current inadequacy of the antibiotic pipeline, there is increasing interest in nontraditional approaches to antibacterial therapies. We define "traditional" agents as small-molecule agents that directly target bacterial components to exert a bacteriostatic or bactericidal effect, and "nontraditional approaches" as antimicrobial therapeutics that work through other means (ie, not a small molecule and/or utilizes a nontraditional target). Due to their atypical features, such therapies may be less susceptible to the emergence of resistance than traditional antibiotics. They include approaches such as monoclonal antibodies, virulence disruptors, immunomodulators, phage therapies, microbiome based therapies, antibiotic potentiators, and antisense approaches. This article discusses both the developmental and regulatory advantages and challenges associated with each of these technologies. By identifying existing regulatory and developmental gaps, we hope to provide a sense of where focusing resources may provide the greatest impact on successful product development. PMID- 28985673 TI - Observation of the Marcus Inverted Region of Electron Transfer from Asymmetric Chemical Doping of Pristine (n,m) Single-Walled Carbon Nanotubes. AB - The concept of electrical energy generation based on asymmetric chemical doping of single-walled carbon nanotube (SWNT) papers is presented. We explore 27 small, organic, electron-acceptor molecules that are shown to tune the output open circuit voltage (VOC) across three types of pristine SWNT papers with varying (n,m) chirality distributions. A considerable enhancement in the observed VOC, from 80 to 440 mV, is observed for SWNT/molecule acceptor pairs that have molecular volume below 120 A3 and lowest unoccupied molecular orbital (LUMO) energies centered around -0.8 eV. The electron transfer (ET) rate constants driving the VOC generation are shown to vary with the chirality-associated Marcus theory, suggesting that the energy gaps between SWNT and the LUMO of acceptor molecules dictate the ET process. When the ET rate constants and the maximum VOC are plotted versus the LUMO energy of the acceptor organic molecule, volcano shaped dependencies, characteristic of the Marcus inverted region, are apparent for three distinct sources of SWNT papers with modes in diameter distributions of 0.95, 0.83, and 0.75 nm. This observation, where the ET driving force exceeds reorganization energies, allows for an estimation of the outer-sphere reorganization energies with values as low as 100 meV for the (8,7) SWNT, consistent with a proposed image-charge modified Born energy model. These results expand the fundamental understanding of ET transfer processes in SWNT and allow for an accurate calculation of energy generation through asymmetric doping for device applications. PMID- 28985675 TI - One-Pot Asymmetric Synthesis of Alkylidene 1-Alkylindan-1-ols Using Bronsted Acid and Palladium Catalysis. AB - A one-pot catalytic enantioselective allylboration/Mizoroki-Heck reaction of 2 bromoaryl ketones has been developed for the asymmetric synthesis of 3 methyleneindanes bearing a tertiary alcohol center. Bronsted acid-catalyzed allylboration with a chiral BINOL derivative was followed by a palladium catalyzed Mizoroki-Heck cyclization, resulting in selective formation of the exo alkene. This novel protocol provides a concise and scalable approach to 1-alkyl-3 methyleneindan-1-ols in high enantiomeric ratios (up to 96:4 er). The potential of these compounds as chiral building blocks was demonstrated with efficient transformation to optically active diol and amino alcohol scaffolds. PMID- 28985674 TI - Iodide-Switched Deposition for the Synthesis of Segmented Pd-Au-Pd Nanorods: Crystal Facet Matters. AB - Segmented metallic nanorods with well-defined shapes and controllable components play an important role on the systematic investigation of their shape-dependent catalytic, electric, and plasmonic properties of metal nanostructures. Unfortunately, the shape and composition of segmented nanorods are difficult to be precisely controlled via colloidal methods. Here, we reported the growth of Pd Au-Pd bimetallic heterostructures by using Au 5-fold twinned bipyramids (BPs) as seeds, with KI as a structure-directing reagent. Through a series of control experiments we revealed that two parameters were identified as critical factors for the growth of segmented Pd-Au-Pd nanorods. First, 5-fold twinned Au BPs with low-index end facets and high-index side facets function as a unique template for directed growth. Second, iodide can switch the deposition of Pd on the Au BPs. A high concentration of iodide is believed to block the high-index facets of the Au BPs and lower the reaction kinetics to promote the selective growth of two Pd segments on the Au BPs. As a result, uniformed segmented Pd-Au-Pd nanorods were obtained. The segmented nanorods exhibit intense extinction in the near-IR range and could be a potential candidate for plasmon-based biological applications such as thermal therapy. PMID- 28985676 TI - Absorptive Dissolution Testing of Supersaturating Systems: Impact of Absorptive Sink Conditions on Solution Phase Behavior and Mass Transport. AB - One of the most commonly used formulation development tools is dissolution testing. However, for solubility enhancing formulations, a simple closed compartment conventional dissolution apparatus operating under sink conditions often fails to predict oral bioavailability and differentiate between formulations. Hence, increasing attention is being paid to combined dissolution absorption testing. The currently available mass transport apparatuses, however, have certain limitations, the most important being the small membrane surface area, which results in slow mass transfer. In this study, a novel high surface area, flow-through absorptive dissolution testing apparatus was developed and tested on a weakly basic model drug, nevirapine. Following optimization of the experimental parameters, the mass transfer attained for a nevirapine solution was 30 times higher in 60 min as compared to a side-by-side diffusion cell. To further evaluate the system, nevirapine powder and commercial tablets were first dissolved at an acidic pH, followed by pH increase, creating a supersaturated solution. Detailed information related to the extent of supersaturation achieved in crystallizing and noncrystallizing systems could be obtained from the combined dissolution-mass transport measurements. Differences in donor cell compartment concentration-time profiles were noted for absorptive versus closed compartment conditions. It is anticipated that this approach could be a promising tool to identify solubility enabling formulations that perform optimally in vivo. PMID- 28985677 TI - Remediation of Cadmium Toxicity by Sulfidized Nano-Iron: The Importance of Organic Material. AB - Nanozerovalent iron (nZVI) is widely used for its ability to remove or degrade environmental contaminants. However, the effect of nZVI-pollutant complexes on organisms has not been tested. We demonstrate the ability of a sulfidized derivative of nZVI (FeSSi) to sorb cadmium (Cd) from aqueous media and alleviate Cd toxicity to a freshwater alga for 32 days. FeSSi particles removed over 80% of the aqueous Cd in the first hour and nearly the same concentration of free Cd remained unbound at the end of the experiment. We found that FeSSi particles with Cd sorbed onto them are an order of magnitude more toxic than FeSSi alone. Further, algal-produced organic material facilitates safer remediation of Cd by FeSSi by decreasing the toxicity of FeSSi itself. We developed a dynamic model to predict the maximum Cd concentration FeSSi can remediate without replacing Cd toxicity with its own. FeSSi can remediate four times as much Cd to phytoplankton populations when organic material is present compared to the absence of organic material. We demonstrate the effectiveness of FeSSi as an environmental remediator and the strength of our quantitative model of the mitigation of nanoparticle toxicity by algal-produced organic material. PMID- 28985678 TI - Aescin Incorporation and Nanodomain Formation in DMPC Model Membranes. AB - The saponin aescin from the horse chestnut tree is a natural surfactant well known to self-assemble as oriented-aggregates at fluid interfaces. Using model membranes in the form of lipid vesicles and Langmuir monolayers, we study the mixing properties of aescin with the phase-segregating phospholipid 1,2 dimyristoyl-sn-glycero-phosphocholine (DMPC). The binary membranes are experimentally studied on different length scales ranging from the lipid headgroup area to the macroscopic scale using small-angle X-ray scattering (SAXS), photon correlation spectroscopy (PCS), and differential scanning calorimetry (DSC) with binary bilayer vesicles and Langmuir tensiometry (LT) with lipid monolayers spread on the surface of aescin solutions. The binary interaction was found to strongly depend on aescin concentration in two well differentiated concentration regimes. Below 7 mol %, the results reveal phase segregation of nanometer-sized aescin-rich domains in an aescin-poor continuous bilayer. Above this concentration, aescin-aescin interactions dominate, which inhibit vesicle formation but lead to the formation of new membrane aggregates of smaller sizes. From LT studies in monolayers, the interaction of aescin with DMPC was shown to be stronger in the condensed phase than in the liquid expanded phase. Furthermore, a destructuring role was revealed for aescin on phospholipid membranes, similar to the fluidizing effect of cholesterol and nonsteroidal anti inflammatory drugs (NSAIDs) on lipid bilayers. PMID- 28985679 TI - Plasmonic-Photonic Interference Coupling in Submicrometer Amorphous TiO2-Ag Nanoarchitectures. AB - In this study, we report the crystallinity effects of submicrometer titanium dioxide (TiO2) nanotube (TNT) incorporated with silver (Ag) nanoparticles (NPs) on surface-enhanced Raman scattering (SERS) sensitivity. Furthermore, we demonstrate the SERS behaviors dependent on the plasmonic-photonic interference coupling (P-PIC) in the TNT-AgNP nanoarchitectures. Amorphous TNTs (A-TNTs) are synthesized through a two-step anodization on titanium (Ti) substrate, and crystalline TNTs (C-TNTs) are then prepared by using thermal annealing process at 500 degrees C in air. After thermally evaporating 20 nm thick Ag on TNTs, we investigate SERS signals according to the crystallinity and P-PIC on our TNT-AgNP nanostructures. (A-TNTs)-AgNP substrates show dramatically enhanced SERS performance as compared to (C-TNTs)-AgNP substrates. We attribute the high enhancement on (A-TNTs)-AgNP substrates with electron confinement at the interface between A-TNTs and AgNPs as due to the high interfacial barrier resistance caused by band edge positions. Moreover, the TNT length variation in (A-TNTs)-AgNP nanostructures results in different constructive or destructive interference patterns, which in turn affects the P-PIC. Finally, we could understand the significant dependency of SERS intensity on P-PIC in (A-TNTs)-AgNP nanostructures. Our results thus might provide a suitable design for a myriad of applications of enhanced EM on plasmonic-integrated devices. PMID- 28985680 TI - Understanding the Effect of Single Cysteine Mutations on Gold Nanoclusters as Studied by Spectroscopy and Density Functional Theory Modeling. AB - Fluorescent metal nanoclusters have generated considerable excitement in nanobiotechnology, particularly in the applications of biolabeling, targeted delivery, and biological sensing. The present work is an experimental and computational study that aims to understand the effects of protein environment on the synthesis and electronic properties of gold nanoclusters. MPT63, a drug target of Mycobacterium tuberculosis, was used as the template protein to synthesize, for the first time, gold nanoclusters at a low micromolar concentration of the protein. Two single cysteine mutants of MPT63, namely, MPT63Gly20Cys (mutant I) and MPT63Gly40Cys (mutant II) were employed for this study. The experimental results show that cysteine residues positioned in two different regions of the protein induce varying electronic states of the nanoclusters depending on the surrounding amino acids. A mixture of five-atom and eight-atom clusters was generated for each mutant, and the former was found to be predominant in both cases. Computational studies, including density functional theory (DFT), frontier molecular orbital (FMO), and natural bond orbital (NBO) calculations, validated the experimental observations. The as-prepared protein stabilized nanoclusters were found to have applications in the imaging of live cells. PMID- 28985681 TI - Identifying the Recognition Site for Selective Trapping of 99TcO4- in a Hydrolytically Stable and Radiation Resistant Cationic Metal-Organic Framework. AB - Effective and selective removal of 99TcO4- from aqueous solution is highly desirable for both waste partitioning and contamination remediation purposes in the modern nuclear fuel cycle, but is of significant challenge. We report here a hydrolytically stable and radiation-resistant cationic metal-organic framework (MOF), SCU-101, exhibiting extremely fast removal kinetics, exceptional distribution coefficient, and high sorption capacity toward TcO4-. More importantly, this material can selectively remove TcO4- in the presence of large excesses of NO3- and SO42-, as even 6000 times of SO42- in excess does not significantly affect the sorption of TcO4-. These superior features endow that SCU-101 is capable of effectively separating TcO4- from Hanford low-level waste melter off-gas scrubber simulant stream. The sorption mechanism is directly unraveled by the single crystal structure of TcO4--incorporated SCU-101, as the first reported crystal structure to display TcO4- trapped in a sorbent material. A recognition site for the accommodation of TcO4- is visualized and is consistent with the DFT analysis results, while no such site can be resolved for other anions. PMID- 28985682 TI - No Evidence for an Association Between Renal Function and Serious Bleeding Events in Patients Treated With Coumarins: A Population-Based Study. AB - BACKGROUND: Although anticoagulation therapy is closely monitored in the Netherlands, coumarin-induced serious bleeding events are still observed. Current literature suggests that renal impairment may contribute to this. OBJECTIVE: To explore the association between renal function and bleeding events during coumarin treatment. METHODS: A nested case-control study was conducted using data from the PHARMO Database Network. Patients hospitalized for a bleeding event during coumarin treatment were selected as cases and matched on sex, birth year, and geographic region to up to 2 controls using coumarins without hospitalization for bleeding. All values of estimated glomerular filtration rates (eGFRs) were selected in the year before index date (case hospitalization date) and compared between cases and controls using logistic regression analyses. RESULTS: In total, 2224 cases were matched to 4398 controls (61% male; mean +/- SD age 75 +/- 11 and 78 +/- 11 years among cases and controls, respectively). Availability of eGFR values was higher among cases compared with controls (mean +/- SD eGFR values 4.5 +/- 7.1 vs 3.2 +/- 5.5), reflected in the significantly shorter time since last eGFR value (at index date, mean +/- SD = 2.7 +/- 3.0 vs 3.8 +/- 3.1 months; odds ratio [OR] = 0.91, 95%CI = 0.89-0.92). No statistically significant difference was found for the mean eGFR value in the year before index date (mean +/- SD 65.7 +/- 22.8 vs 64.6 +/- 20.9 mL/min/1.73 m2; OR per 10 units [95%CI] = 0.99 [0.96 1.02]). CONCLUSIONS: No association between renal function and serious bleeding events during coumarin treatment was observed. PMID- 28985683 TI - Effects of botulinum toxin A therapy and multidisciplinary rehabilitation on lower limb spasticity classified by spastic muscle echo intensity in post-stroke patients. AB - OBJECTIVES: The purpose of the present study was to investigate retrospectively the relationship between botulinum toxin type A plus multidisciplinary rehabilitation and muscle echo intensity in post-stroke patients with spasticity. The primary aim was to investigate whether the effects of the intervention on the improvement of spasticity depend on muscle echo intensity, and the secondary aim was to investigate whether the motor function of the lower limbs depends on muscle echo intensity. METHODS: A 12-day inpatient protocol was designed for 102 post-stroke patients with spasticity due to lower limb paralysis. Muscle echo intensity of the triceps surae muscle was measured by ultrasonography, and the patients were categorized into four groups based on Heckmatt scale grades (Grades I-IV). RESULTS: All four groups classified by the Heckmatt scale showed significant pre-to-post-intervention differences in the knee and ankle modified Ashworth scale scores (p < 0.05). Grades I-III patient groups showed a significant improvement in lower limb motor function following intervention. Grade IV patients did not show a significant improvement in lower limb motor function. CONCLUSIONS: We observed significant improvements in the modified Ashworth scale scores after botulinum toxin type A and multidisciplinary rehabilitation therapy on post-stroke patients with spasticity. Although patients with lower muscle echo intensity demonstrated improvements in motor function, the improvement was poor in those with higher muscle echo intensity. PMID- 28985684 TI - Microencapsulation of probiotics by efficient vibration technology. AB - The target site of action of probiotics is the intestine. They must be surviving the stomach acidic condition before reaching the target site. Three probiotic bacteria were microencapsulated in sodium alginate beads using a sophisticated microencapsulation technology provided by BUCHI B-390. This study reports the tolerance of the different microencapsulated Lactobacillus at low pH using simulated gastric juice, comparing it with the tolerance of free bacteria. The three microencapsulated strains displayed time-dependent acid sensitivity at pH values under 3.0. At pH 2.0, a dramatic reduction in bacterial survival occurred after 5 min, with only L. casei surviving after 30 min, with 75% survival. At pH 2.5 microencapsulated L. casei survived for 90 , L. reuteri survived for 60 and L. bulgaricus survived for only 30 min, respectively. The microencapsulation technology used in this study may effectively protect Lactobacillus from gastric conditions and permit comparisons between strains. PMID- 28985685 TI - Effectiveness of the Simultaneous Stretching of the Achilles Tendon and Plantar Fascia in Individuals With Plantar Fasciitis. AB - BACKGROUND: Since the plantar fascia and the Achilles tendon are anatomically connected, it is plausible that stretching of both structures simultaneously will result in a better outcome for plantar fasciitis. METHODS: Fifty participants aged 40 to 60 years with a history of plantar fasciitis greater than 1 month were recruited. They were prospectively randomized into 2 groups. Group 1 was instructed to stretch the Achilles tendon while group 2 simultaneously stretched the Achilles tendon and plantar fascia. RESULTS: After 4 weeks of both stretching protocols, participants in group 2 demonstrated a significantly greater pressure pain threshold than participants in group 1 ( P = .040) with post hoc analysis. No significant differences between groups were demonstrated in other variables ( P > .05). Concerning within-group comparisons, both interventions resulted in significant reductions in pain at first step in the morning and average pain at the medial plantar calcaneal region over the past 24 hours, while there were increases in the pressure pain threshold, visual analog scale-foot and ankle score, and range of motion in ankle dorsiflexion ( P < .001). More participants in group 2 described their symptoms as being much improved to being completely improved than those in group 1. CONCLUSION: The simultaneous stretching of the Achilles tendon and plantar fascia for 4 weeks was a more effective intervention for plantar fasciitis. Patients who reported complete relief from symptoms at the end of the 4-week intervention in the simultaneous stretching group (n = 14; 56%) were double that of the stretching of the Achilles tendon-only group (n = 7; 28%). LEVEL OF EVIDENCE: II, lesser quality RCT or prospective comparative study. PMID- 28985686 TI - Are Older Adults Willing to Consider New Strategies to Reduce Stroke Risk? AB - Atrial fibrillation (AF) is a common arrhythmia that increases patients' risk of stroke, and determining an optimal prevention therapy is a preference-sensitive decision appropriate for shared decision making (SDM). Utilizing community-based focus groups, we explored beliefs and values around options for stroke prevention. Interview transcripts from five independent focus groups were qualitatively assessed and organized into themes. Most participants were taking a blood thinner (93%) and more than half of participants (64%) reported having AF. Few participants were familiar with newer therapies. Qualitative analysis revealed three themes: (a) fearing loss of self-control through debilitating stroke, (b) recognizing uncertainty in how to weigh risks and benefits of new treatments, and (c) needing mutual respect between clinicians and patients to consider new/alternative treatment regimens. These findings help direct future research efforts examining optimal timing for SDM and decision aids to promote mutual respect. PMID- 28985687 TI - Evaluating the swelling, erosion, and compaction properties of cellulose ethers. AB - Swelling, erosion, deformation, and consolidation properties can affect the performance of cellulose ethers, the most commonly used matrix former in hydrophilic sustained tablet formulations. The present study was designed to comparatively evaluate the swelling, erosion, compression, compaction, and relaxation properties of the cellulose ethers in a comprehensive study using standardised conditions. The interrelationship between various compressional models and the inherent deformation and consolidation properties of the polymers on the derived swelling and erosion parameters are consolidated. The impact of swelling (Kw) on erosion rates (KE) and the inter-relationship between Heckel and Kawakita plasticity constants was also investigated. It is evident from the findings that the increases in both substitution and polymer chain length led to higher Kw, but a lower KE; this was also true for all particle size fractions regardless of polymer grade. Smaller particle size and high substitution levels tend to increase the relative density of the matrix but reduce porosity, yield pressure (Py), Kawakita plasticity parameter (b-1) and elastic relaxation. Both KW versus KE (R2 = 0.949-0.980) and Py versus. b-1 correlations (R2 = 0.820 0.934) were reasonably linear with regards to increasing hydroxypropyl substitution and molecular size. Hence, it can be concluded that the combined knowledge of swelling and erosion kinetics in tandem with the in- and out-of-die compression findings can be used to select a specific polymer grade and further to develop and optimize formulations for oral controlled drug delivery applications. PMID- 28985688 TI - Diagnosis and management of pancreatic exocrine insufficiency (PEI) in primary care: consensus guidance of a Canadian expert panel. AB - BACKGROUND: Pancreatic exocrine insufficiency (PEI) results in maldigestion due to inadequate activity of pancreatic enzymes in the small bowel. PEI can arise from a variety of medical conditions that reduce enzyme synthesis within the pancreatic parenchyma or from secondary factors that may occur despite optimal parenchymal function, such as pancreatic duct obstruction or impaired or poorly synchronized enzyme release. PURPOSE: To provide practical guidance for primary care physicians managing patients who are at risk of PEI or who present with symptoms of PEI. METHODS: For each of six key clinical questions identified by the authors, PubMed searches were conducted to identify key English-language papers up to April 2017. Forward and backward searches on key articles were conducted using Web of Science. Clinical recommendations proposed by the co chairs (P.D. and C.T.) were vetted and approved based on the authors? CONSENSUS: FINDINGS: The most characteristic symptom of PEI is steatorrhea ? voluminous, lipid-rich stools; other common signs and symptoms include unexplained weight loss and deficiencies of fat-soluble vitamins and other micronutrients. Pancreatic enzyme replacement therapy (PERT) can relieve symptoms and long-term sequelae of PEI. Diagnosis of PEI and initiation of PERT are usually the responsibility of gastroenterology specialists. However, primary care physicians (PCPs) are well positioned to identify potential cases of PEI and to participate in the collaborative, long-term management of patients already seen by a specialist. CONCLUSIONS: In this document, a panel of Canadian gastroenterologists has conducted a critical review of the literature on PEI and PERT and has developed practical diagnostic and treatment recommendations for PCPs. These recommendations provide guidance on identifying patients at risk of PEI, the triggers for PEI testing and referral, and best practices for co managing patients with confirmed PEI. PMID- 28985689 TI - Effect of age, period and birth-cohort on the frequency of glucose-6-phosphate dehydrogenase deficiency in Sardinian adults. AB - BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an inherited disorder common in Sardinia. In this study, the frequency variation of G6PD deficiency across age groups and birth cohorts was investigated using Age-Period Cohort analysis. METHODS: Data were collected from the clinical records of 11,252 patients (6975 women, age range 17-94 years) who underwent endoscopy between 2000 and 2016 at a teaching hospital (University of Sassari), Italy. G6PD status was assessed by enzymatic assay based on G6PD/6GPD ratio. A Poisson log-linear regression model was used to identify age and time trend in G6PD deficiency. RESULTS: Enzyme deficiency was detected in 11.4% of the entire cohort (men: 7.9%; women: 13.6%). Age-Period-Cohort analysis showed no inflection points across age groups, especially after age 80. The effects of time period and birth cohorts on G6PD deficiency were negligible (frequencies before and after 1950 were 11.0% and 11.8%, respectively). CONCLUSIONS: These findings indicate that the frequency of G6PD deficiency does not vary significantly in oldest subjects. The lack of evidence for selection across the malaria eradication time may be explained by other factors, including somatic cell selection or misclassification of heterozygotes women as G6PD normal in the older birth cohorts. Additional molecular studies may help clarify these issues. Key message The frequency of glucose-6-phosphate dehydrogenase deficiency is stable across age groups and does not vary in generations born before or after malaria eradication. PMID- 28985690 TI - Influence of high-flow modified ultrafiltration on brain oxygenation and perfusion during surgery for children with ventricular septal defects: a pilot study. AB - BACKGROUND: Modified ultrafiltration (MUF) can be performed in infants with ventricular septal defects (VSDs) after cardiopulmonary bypass (CPB) to reduce haemodilution and its potential adverse effects. High-flow MUF might reduce ultrafiltration duration and hasten the necessary correction of haemodilution during CPB. However, its influence on brain oxygenation remains controversial. OBJECTIVE: This non-randomized, prospective, pilot study aimed to investigate the influence of high-flow MUF on brain oxygenation in infants with VSDs. METHODS: High-flow MUF (>=20 mL/kg/min) was performed in twenty infants. Brain oxygen saturation (rSO2) and tissue haemoglobin index (tHI) were non-invasively and continuously measured intraoperatively using near-infrared spectroscopy (NIRS). Transcranial Doppler non-invasively detected the mean flow velocity of the middle cerebral artery (Vmean). RESULTS: rSO2 increased significantly during MUF, as did tHI, Vmean, mean arterial pressure and haematocrit (all p<0.05). No correlation was found between changes in rSO2 and changes in other parameters (all p>=0.05). CONCLUSION: In infants with ventricular septal defects managed with CPB during VSDs repair, high-flow MUF did not reduce brain oxygenation. PMID- 28985691 TI - Comparative Outcomes Between Step-Cut Lengthening Calcaneal Osteotomy vs Traditional Evans Osteotomy for Stage IIB Adult-Acquired Flatfoot Deformity. AB - BACKGROUND: The forefoot abduction component of the flexible adult-acquired flatfoot can be addressed with lengthening of the anterior process of the calcaneus. We hypothesized that the step-cut lengthening calcaneal osteotomy (SLCO) would decrease the incidence of nonunion, lead to improvement in clinical outcome scores, and have a faster time to healing compared with the traditional Evans osteotomy. METHODS: We retrospectively reviewed 111 patients (143 total feet: 65 Evans, 78 SLCO) undergoing stage IIB reconstruction followed clinically for at least 2 years. Preoperative and postoperative radiographs were analyzed for the amount of deformity correction. Computed tomography (CT) was used to analyze osteotomy healing. The Foot and Ankle Outcome Scores (FAOS) and lateral pain surveys were used to assess clinical outcomes. Mann-Whitney U tests were used to assess nonnormally distributed data while chi2 and Fisher exact tests were used to analyze categorical variables (alpha = 0.05 significant). RESULTS: The Evans group used a larger graft size ( P < .001) and returned more often for hardware removal ( P = .038) than the SLCO group. SLCO union occurred at a mean of 8.77 weeks ( P < .001), which was significantly lower compared with the Evans group ( P = .02). The SLCO group also had fewer nonunions ( P = .016). FAOS scores improved equivalently between the 2 groups. Lateral column pain, ability to exercise, and ambulation distance were similar between groups. CONCLUSION: Following SLCO, patients had faster healing times and fewer nonunions, similar outcomes scores, and equivalent correction of deformity. SLCO is a viable technique for lateral column lengthening. LEVEL OF EVIDENCE: Level III, retrospective cohort study. PMID- 28985692 TI - Comprehensive blood conservation program in a new congenital cardiac surgical program allows bloodless surgery for the Jehovah Witness and a reduction for all patients. AB - BACKGROUND: Cardiac surgery on Jehovah's Witnesses (JW) can be challenging, given the desire to avoid blood products. Establishment of a blood conservation program involving the pre-, intra- and post-operative stages for all patients may lead to a minimized need for blood transfusion in all patients. METHODS: Pre-operatively, all JW patients were treated with high dose erythropoietin 500 IU/kg twice a week. JW patients were compared to matching non-JW patients from the congenital cardiac database, two per JW to serve as control. Blood use, ventilation time, bypass time, pre-operative hematocrit, first in intensive care unit (ICU) and at discharge and 24 hour chest drainage were compared. Pre-operative huddle, operating room huddle and post-operative bedside handoff were done with the congenital cardiac surgeon, perfusionist, anesthesiologist and intensive care team in all patients for goal alignment. RESULTS: Five JW patients (mean weight 24.4 +/- 25.0 Kg, range 6.3 - 60 Kg) were compared to 10 non-JW patients (weight 22.0 +/- 22.8 Kg, range 6.2 - 67.8 Kg). There was no difference in bypass, cross clamp, time to extubation (0.8 vs. 2.1 hours), peak inotrope score (2.0 vs. 2.3) or chest drainage. No JW patient received a blood product compared to 40% of non JW. The pre-operative hematocrit (Hct) was statistically greater for the JW patients (46.1 +/- 3.3% vs. 36.3 +/- 4.7%, p<0.001) and both ICU and discharge Hct were higher for the JW (37 +/- 1.8% vs 32.4 +/- 8.0% and 41 +/- 8.1% vs 34.8 +/- 7.9%), but did not reach statistical significance. All patients had similar blood draws during the hospitalization (JW x 18 mL/admission vs non-JW 20 mL/admission). CONCLUSION: The continuous application and development of blood conservation techniques across the continuum of care allowed bloodless surgery for JW and non-JW patients alike. Blood conservation is a team sport and to make significant strides requires participation and input by all care providers. PMID- 28985693 TI - Assessing the depth of isoflurane anaesthesia during cardiopulmonary bypass. AB - INTRODUCTION: Bispectral index (BIS) and monitoring of end-tidal concentration may be associated with a reduction in the incidence of awareness during volatile based general anaesthesia. An analogue of end-tidal concentration during cardiopulmonary bypass (CPB) is measuring exhausted isoflurane concentration from the oxygenator as an estimate to blood and, so, brain concentration. The aim of this study was to determine the relationships between oxygenator exhaust and blood concentrations of isoflurane and the BIS score during CPB when administering isoflurane into the sweep gas supply to the oxygenator. METHODS: Seventeen patients undergoing elective cardiac surgery using CPB and isoflurane with BIS monitoring were recruited in a single-centre university hospital. Isoflurane gas was delivered via a calibrated vaporiser at the beginning of anaesthetic induction. Radial arterial blood samples were collected after the initiation of CPB and before aortic cross-clamping, which were analysed for isoflurane by gas chromatography and mass spectrometry. The BIS score and the concentration of exhausted isoflurane from the oxygenator membrane, as measured by an anaesthetic gas analyser, were recorded at the time of blood sampling. RESULTS: The mean duration of anaesthetic induction to arterial blood sampling was 90 min (95%CI: 80,100). On CPB, the median BIS was 39 (range, 7-43) and the mean oxygenator exhaust isoflurane concentration was 1.24 +/- 0.21%. No significant correlation was demonstrated between BIS with arterial isoflurane concentration (r=-0.19, p=0.47) or oxygenator exhaust isoflurane concentration (r=0.07, p=0.80). Mixed-venous blood temperature was moderately correlated to BIS (r=0.50, p=0.04). Oxygenator exhaust isoflurane concentration was moderately, positively correlated with its arterial concentration (r=0.64, p<0.01). DISCUSSION: In conclusion, in patients undergoing heart surgery with CPB, the findings of this study indicate that, whilst oxygenator exhaust concentrations were significantly associated with arterial concentrations of isoflurane, neither had any association with the BIS scores, whereas body temperature has moderate positive correlation. PMID- 28985694 TI - Domestic Violence and the Victim/Offender Overlap Across the Life Course. AB - The current article examined the overlap of domestic violence across the life course, connecting childhood abuse and adolescent dating victimization to adult intimate partner victimization, and the connection between these behaviors and adult domestic violence perpetration against partners and children. Using three waves of Add Health data, the study found that childhood and adolescent domestic victimization were directly and indirectly linked to adult intimate partner victimization and that domestic violence perpetration also played a role. These findings indicate that offending must be accounted for in tracking patterns of victimization over the life course and that the overlap must more directly be reconciled in current criminal justice policy. PMID- 28985695 TI - Techniques of Neutralization: A Brain Network Perspective. AB - Sykes and Matza introduced neutralization theory in 1957 to explain how juvenile delinquents retain a positive self-image when engaging in delinquent acts. Since then, aspects of neutralization theory have been incorporated into sociological and criminological theories to explain socially deviant behavior. Functional brain mapping research utilizing advanced magnetic resonance imaging techniques has identified complex, intrinsically organized, large-scale brain networks. Higher order operations commonly attributed to three brain networks (default mode network [DMN], central executive network [CEN], salience network [SN]) align closely with neutralization theory. This article briefly discusses brain networks in general and the DMN, CEN, and SN specifically. It also discusses how these networks are involved when engaging in the use of techniques of neutralization and offers implications for future research. PMID- 28985696 TI - A new prosthetic alignment device to read and record prosthesis alignment data. AB - Prosthetic alignment is an essential process to rehabilitate patients with amputations. This study presents, for the first time, an invented device to read and record prosthesis alignment data. The digital device consists of seven main parts: the trigger, internal shaft, shell, sensor adjustment button, digital display, sliding shell, and tip. The alignment data were read and recorded by the user or a computer to replicate prosthesis adjustment for future use or examine the sequence of changes in alignment and its effect on the posture of the patient. Alignment data were recorded at the anterior/posterior and medial/lateral positions for five patients. Results show the high level of confidence to record alignment data and replicate adjustments. Therefore, the device helps patients readjust their prosthesis by themselves, or prosthetists to perform adjustment for patients and analyze the effects of malalignment. PMID- 28985697 TI - Characterization of Prepractice Injury Prevention Exercises of High School Athletic Teams. AB - BACKGROUND: Static and dynamic exercises are performed before activity to decrease injury risk and increase performance. Although evidence supports using dynamic over static stretching and performing Federation Internationale de Football Association (FIFA) 11+ as a dynamic prepractice routine, we do not know the frequency at which these exercises are utilized in high school populations. HYPOTHESIS: We hypothesize that there is a wide variety of preparticipation exercises performed by high school athletes, and that few high school teams perform FIFA 11+ as an injury prevention program in its entirety. STUDY DESIGN: Observational study. LEVEL OF EVIDENCE: Level 4. METHODS: High school prepractice routines were observed for 185 teams (football, soccer, basketball, and lacrosse) over 1 season. The percentages of team warm-up routines that included components of FIFA 11+ were calculated, and the chi-square test was used to compare sex, sport, and level of competition. RESULTS: Of a total 644 warm-up observations, 450 (69.9%) included only non-FIFA 11+ exercises, 56 (8.7%) included at least 1 FIFA 11+ exercise, and 38 (5.9%) included only jogging; 69 (10.6%) consisted only of sport-specific activities. The type of warm-up differed significantly between males and females ( P = 0.002), sports ( P < 0.001), and level of competition ( P < 0.001). Static stretching and athletes stretching on their own were observed in 14% and 15% of all observations. No team performed the FIFA 11+ injury prevention routine in its entirety. CONCLUSION: The type of warm-up differed by sex, sport, and level of competition. Static stretching was performed more frequently than anticipated, and an entire FIFA 11+ warm-up was never performed. CLINICAL RELEVANCE: We need to identify the exercises that decrease injury and increase performance and better inform the athletic population about the risks and benefits of static and dynamic warm-up programs. PMID- 28985700 TI - Telepsychiatry 2.0. PMID- 28985698 TI - Application of real-time quantitative PCR assays for detecting marine Brucella spp. in fish. AB - Brucella ceti and Brucella pinnipedialis have been documented as occurring in marine mammals, and B. ceti has been identified in 3 naturally acquired human cases. Seroconversion and infection patterns in Pacific Northwest harbor seals ( Phoca vitulina richardii) and North Atlantic hooded seals ( Cystophora cristata) indicate post-weaning exposure through prey consumption or lungworm infection, suggesting fish and possibly invertebrates play an epizootiologic role in marine Brucella transmission and possible foodborne risk to humans. We determined if real-time quantitative PCR (qPCR) assays can detect marine Brucella DNA in fish DNA. Insertion sequence (IS) 711 gene and sequence type (ST)27 primer-probe sets were used to detect Brucella associated with marine mammals and human zoonotic infections, respectively. First, DNA extracts from paired-species fish (containing 2 species) samples were tested and determined to be Brucella DNA negative using both IS 711 and ST27 primer-probe sets. A representative paired species fish DNA sample was spiked with decreasing concentrations of B. pinnipedialis DNA to verify Brucella detection by the IS 711 primer-probe within fish DNA. A standard curve, developed using isolated DNA from B. pinnipedialis, determined the limit of detection. Finally, the IS 711 primer-probe was used to test Atlantic cod ( Gadus morhua) DNA extracts experimentally infected with the B. pinnipedialis hooded seal strain. In culture-positive cod tissue, the IS 711 limit of detection was ~1 genome copy of Brucella. Agreement between culture and PCR results for the 9 positive and 9 negative cod tissues was 100%. Although a larger sample set is required for validation, our study shows that qPCR can detect marine Brucella in fish. PMID- 28985702 TI - Descriptive Epidemiology of Injuries Sustained in National Collegiate Athletic Association Men's and Women's Volleyball, 2013-2014 to 2014-2015. AB - BACKGROUND: There were 18,844 volleyball players in the National Collegiate Athletic Association (NCAA) in the 2014-2015 academic year. Little research has examined sex-based differences among these athletes. PURPOSE: To examine injury epidemiology in NCAA men's and women's volleyball athletes. STUDY DESIGN: Descriptive epidemiology study. LEVEL OF EVIDENCE: Level 3. METHODS: Injury surveillance data from the 2013-2014 through 2014-2015 academic years were obtained from the NCAA Injury Surveillance Program for 6 men's and 33 women's collegiate volleyball teams. Injury rates per 1000 athlete-exposures (AEs) and injury rate ratios (IRRs) with 95% CIs were calculated. Time-loss (TL) injuries resulted in participation restriction for at least 24 hours, and non-time-loss (NTL) injuries resulted in participation restriction of less than 24 hours. RESULTS: Overall, 83 and 510 injuries were reported in men and women, respectively, leading to injury rates of 4.69 and 7.07 per 1000 AEs. The injury rate was greater in women than men (IRR, 1.51; 95% CI, 1.19-1.90). TL injury rates were 1.75 and 2.62 per 1000 AEs for men and women, respectively. The ankle was the most commonly injured body part among TL injuries (men, 25.8%; women, 24.3%); the knee was the most commonly injured body part among NTL injuries (men, 25.5%; women, 16.3%). Among TL injuries, common diagnoses included sprains (men, 25.8%; women, 31.2%) and concussions (men, 19.4%; women, 14.8%). Most TL concussions were due to ball contact (men, 83.3%; women, 53.6%). Compared with men, women had a greater NTL overuse injury rate (IRR, 3.47; 95% CI, 1.61-7.46). Compared with women, men had a greater TL injury rate associated with ball contact (IRR, 2.24; 95% CI, 1.07-4.68). CONCLUSION: There are differences in injury patterns and rates between male and female intercollegiate volleyball players. Although a limited-contact sport, a notable number of concussions were sustained, mostly from ball contact. CLINICAL RELEVANCE: Understanding injury patterns may aid clinicians in injury diagnosis, management, and prevention. PMID- 28985703 TI - Escalation of extracorporeal life support as a bridge to lung transplantation in end-stage lung disease. AB - Extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplant (LTx) is not uncommon, but it is not commonplace yet. We present a case of a 45-year old man with cystic fibrosis with recent deterioration in lung function who was initially supported with veno-venous (VV) ECMO. However, he subsequently required conversion to veno-veno-arterial (VVA) ECMO. After 21 days of support, he underwent double lung transplantation, with an uneventful postoperative course. This case shows that, in patients with end-stage respiratory failure awaiting lung transplantation, extracorporeal life support may require escalation to improve gas exchange and address circulatory requirements. PMID- 28985704 TI - Extracorporeal membrane oxygenation for Kawasaki disease: two case reports and the Extracorporeal Life Support Organization experience 1999-2015. AB - Kawasaki disease is usually a limited illness of early childhood. However, life threatening cardiac manifestations can occur, either at acute presentation or as a consequence of coronary arterial involvement. We report the successful use of veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) for cardiac support in two children with Kawasaki disease: one with acute Kawasaki disease shock syndrome, the other with complications of coronary arteritis and subsequent surgery. We also reviewed the reported experience in the ELSO database and available literature. PMID- 28985705 TI - Accuracy of the Spectrum Medical M4 and Terumo CDI 500 compared to the Radiometer ABL90 FLEX benchtop blood analyzer. AB - The benchtop blood analyzer is the gold standard for blood oxygen saturation (SO2) and hemoglobin (Hb) analysis. However, the benchtop analyzer only provides values at a given point in time. In the field of cardiovascular perfusion and the practice of cardiopulmonary bypass (CPB), continuous measurement of SvO2 and hemoglobin values have become commonplace. Two devices currently available which monitor these values are the Terumo CDI 500 and Spectrum Medical M4. A retrospective study was conducted to examine the accuracy of the M4 technology and the CDI 500 as they compare to each other and the ABL90 FLEX, a benchtop blood gas analyzer. The data revealed the magnitude of mean differences were small, even when significant. However, the 95% Limits of Agreement were too large for either device to allow substitution of the CDI 500 and M4 hemoglobin or SvO2 values for ABL90 values. As recommended by the manufacturers, the CDI 500 and M4 should only be used as a trending device. PMID- 28985706 TI - A total eclipse...or a partial eclipse. PMID- 28985707 TI - Simultaneous pain intensity rating and quantification of ischemia throughout exercise and recovery in proximal versus distal arterial claudication. AB - Data on simultaneous hemodynamic changes and pain rating estimation in arterial claudication while walking are lacking. This study was conducted to determine if a difference in transcutaneous oxygen pressure (tc pO2) exists between proximal and distal localization at pain appearance (PAINapp), maximal pain (PAINmax) and pain relief (PAINrel) in proximal or distal claudication and if a relationship exists between tc pO2 changes and pain intensity. We analyzed the pain rating (Visual Analog Scale (VAS)) to lower limb ischemia, measured with the decrease from rest of oxygen pressure (DROP) tc pO2 index during constant-load treadmill tests in patients with calf ( n = 41) or buttock ( n = 19) claudication. Calves versus buttocks results were analyzed with ANOVA tests. The R2 correlation coefficient between individual VAS versus DROP was calculated. Ischemia intensity versus pain rating changes were correlated. Significant ischemia was required for pain appearance, but pain disappeared despite the persistence of ischemia. We observed no statistical difference for DROP at PAINapp, PAINmax or PAINrel between proximal or distal claudication. A significant correlation between pain rating versus DROP was found: from PAINapp to PAINmax, R2 = 0.750 (calves) and 0.829 (buttocks), and from PAINmax to PAINrel, R2 = 0.608 (calves) and 0.560 (buttocks); p<0.05. Pain appeared after a significant decrease of hemodynamic parameters but disappeared while parameters were not normalized. No difference in pain rating was found in proximal versus distal claudication. PMID- 28985708 TI - Images in Vascular Medicine: Blue rubber bleb nevus syndrome: A rare cause of gastrointestinal bleeding and vascular anomaly in children. PMID- 28985709 TI - Detection of Treponema phagedenis-like antibodies in serum and bulk milk from cows with and without digital dermatitis. AB - Digital dermatitis (DD) in dairy cows is a widespread disease linked to infection with Treponema. The traditional diagnostic method is clinical inspection, which is subjective and laborious. We explored the performance of 4 different immunogenic proteins from Treponema phagedenis in a new antibody ELISA for analysis of serum or milk. Analysis of samples from 390 cows in 25 herds showed that the ELISA could distinguish the majority of cows with DD from healthy cows. By changing the cutoff and applying parallel or serial testing, high sensitivity or specificity could be achieved. The investigation indicated that aggregated test results can be useful in the assessment of a herd's DD status. In addition, analysis of bulk tank milk samples showed good agreement with results from individual cows. The test system could be useful in research on the epidemiology and immunology of DD. PMID- 28985710 TI - Early-life exposures and Johne's disease risk in zoo ruminants. AB - Johne's disease, caused by Mycobacterium avium subsp. paratuberculosis (MAP), is a chronic, progressive bacterial enteritis of ruminants that can cause serious losses in both livestock and exotic species. Infection risk in exotic ruminants is associated with maternal infection status, but the effect of other herdmates on risk of infection has not been reported, to our knowledge. We conducted a retrospective cohort study to evaluate the association between MAP infection status and early-life contact with infected herdmates. The study population included 3,234 individuals representing 128 species at San Diego Zoo Global facilities between 1991 and 2010. Animal movement, health, and pathology records were used to trace enclosure-sharing contacts between members of the study population and any MAP-infected animal. Contact-days were counted by age of the reference animal and the number of unique infected individuals contacted. Herdmate infection status was stratified by stage of infection (180 d prior to diagnosis), age, and whether relevant lesions were found at autopsy. Having an infected herdmate was a strong risk factor for infection (OR = 4.4; 95% CI: 1.9 10.3), and each method of defining herdmate infection status showed significant differences in infection risk. The best predictor was number of contact-days within the first week of life, with a 2-fold increase in risk associated with each doubling in the number of contact-days (OR = 2.1; 95% CI: 1.1-4.0). We conclude that early contact with infected animals is an important predictor of MAP infection risk, although the effect size is smaller than that previously described for maternal infection status. PMID- 28985711 TI - Genome-wide analysis of rice cis-natural antisense transcription under cadmium exposure using strand-specific RNA-Seq. AB - BACKGROUND: The elucidation of novel transcripts and their expression in response to various stress conditions is necessary to understand the transcriptional network of plants as an adaptation to biotic and abiotic stresses. We performed strand-specific RNA-Seq (ssRNA-Seq) on rice exposed to cadmium (Cd) for 24 h and investigated the expression of cis-natural antisense transcripts (cis-NATs), a class of endogenous coding or non-protein-coding RNAs with sequence complementarity to the opposite strands of RAP transcripts. RESULTS: Many RAP transcripts possessed cis-NATs and these cis-NATs were responsive to some extent. Cis-NATs were upregulated from 26, 266 and 409 RAP gene loci, while 2054, 2501 and 2825 RAP transcripts were upregulated from 38,123 RAP loci under high Cd exposure in roots at 1, 12 and 24 h, respectively. In addition, most of the upregulated cis-NATs showed little upregulation under ABA or cold treatment. A number of cis-NATs were upregulated from less than 35 RAP gene loci in different tissue and time-point combinations under low Cd exposure, suggesting that cis NATs respond to environmental stress. Furthermore, 409 RAP transcripts with upregulated cis-NATs were classified into three groups based on the expression of the RAP transcripts from the opposite DNA strand, including 138 upregulated, 128 invariable, and 143 downregulated transcripts, although the responses of cis-NATs and RAP transcripts were not always correlated. CONCLUSIONS: We have shown that the cis-NATs identified by ssRNA-Seq analysis are novel genes and that some of them are stress-specific and show different responses depending on the degree of stress and tissue. These results improve our understanding of the complete molecular mechanism of plant adaptation to Cd exposure. PMID- 28985712 TI - An integrative approach to predicting the functional effects of small indels in non-coding regions of the human genome. AB - BACKGROUND: Small insertions and deletions (indels) have a significant influence in human disease and, in terms of frequency, they are second only to single nucleotide variants as pathogenic mutations. As the majority of mutations associated with complex traits are located outside the exome, it is crucial to investigate the potential pathogenic impact of indels in non-coding regions of the human genome. RESULTS: We present FATHMM-indel, an integrative approach to predict the functional effect, pathogenic or neutral, of indels in non-coding regions of the human genome. Our method exploits various genomic annotations in addition to sequence data. When validated on benchmark data, FATHMM-indel significantly outperforms CADD and GAVIN, state of the art models in assessing the pathogenic impact of non-coding variants. FATHMM-indel is available via a web server at indels.biocompute.org.uk. CONCLUSIONS: FATHMM-indel can accurately predict the functional impact and prioritise small indels throughout the whole non-coding genome. PMID- 28985713 TI - Patients with glycogen storage diseases undergoing anesthesia: a case series. AB - BACKGROUND: Glycogen storage diseases are rare genetic disorders of glycogen synthesis, degradation, or metabolism regulation. When these patients are subjected to anesthesia, perioperative complications can develop, including hypoglycemia, rhabdomyolysis, myoglobinuria, acute renal failure, and postoperative fatigue. The objective of this study was to describe the perioperative course of a cohort of patients with glycogen storage diseases. METHODS: This is a retrospective review of patients with glycogen storage diseases undergoing anesthetic care at our institution from January 1, 1990, through June 30, 2015 to assess perioperative management and outcomes. RESULTS: We identified 30 patients with a glycogen storage disease who underwent 41 procedures under anesthesia management. Intraoperative lactic acidosis developed during 4 major surgeries (3 liver transplants, 1 myectomy), and in all cases resolved within 24 postoperative hours. Lactated Ringer solution was used frequently. Preoperative and intraoperative hypoglycemia was noted in some patients with glycogen storage disease type I, all of which responded to administration of dextrose-containing solutions. No serious postoperative complications occurred. CONCLUSIONS: Patients with glycogen storage disease, despite substantial comorbid conditions, tolerates the anesthetic management without major complications. Several patients who experienced self-limited metabolic acidosis were undergoing major surgical procedures, during which acidosis could be anticipated. Close monitoring and management of blood glucose levels of patients with glycogen storage disease type I is prudent. PMID- 28985715 TI - Acute transient spinal paralysis and cardiac symptoms following an accidental epidural potassium infusion - a case report. AB - BACKGROUND: To describe a case of an accidental epidural potassium infusion leading to an acute transient spinal paralysis and cardiac symptoms and review the literature on that topic. CASE PRESENTATION: We report the case of an accidental infusion of 900 mg potassium chloride 7.45% (KCl) into the epidural space, which occurred during epidural analgesia in a 74-year-old patient suffering from immobilization due to lumbar back pain as well as from a paralytic Ileus. The event was resulting in vegetative symptoms, such as tachycardia and hypertension accompanied by a motor complete tetraplegia (AIS B) sub C2 with respiratory depression. The endotracheal intubation was necessary. The patient was treated with 40 mg dexamethasone intravenously, as well an epidural lavage with sodium chloride solution 0.9% (NaCl) through the epidural catheter. The neurologic symptoms completely resolved within five days. An elevation of troponin-T values and a reduced left ventricular ejection fraction (LVEF) of 40% accompanied by transient pectanginous pain were documented. An exertional dyspnea remained. CONCLUSIONS: A symptom complex with elevated sympathetic nervous system activity up to a stress cardiomyopathy is possible following epidural potassium infusion. Additionally, generalized pain and muscle spasticity evolve and a progressive acute spinal cord injury syndrome can occur within minutes, accompanied by respiratory depression. Treatment consists of early intensive care and the symptomatic therapy of the associated symptoms, leading in most of the reported cases to a good clinical outcome. PMID- 28985714 TI - Unhealthy smokers: scopes for prophylactic intervention and clinical treatment. AB - BACKGROUND: Globally, tobacco use causes approximately 6 million deaths per year, and predictions report that with current trends; more than 8 million deaths are expected annually by 2030. Cigarette smokings is currently accountable for more than 480,000 deaths each year in United States (US) and is the leading cause of preventable death in the US. On average, smokers die 10 years earlier than nonsmokers and if smoking continues at its current proportion among adolescents, one in every 13 Americans aged 17 years or younger is expected to die prematurely from a smoking-related illness. Even though there has been a marginal smoking decline of around 5% in recent years (2005 vs 2015), smokers still account for 15% of the US adult population. What is also concerning is that 41,000 out of 480,000 deaths results from secondhand smoke (SHS) exposure. Herein, we provide a detailed review of health complications and major pathological mechanisms including mutation, inflammation, oxidative stress, and hemodynamic and plasma protein changes associated with chronic smoking. Further, we discuss prophylactic interventions and associated benefits and provide a rationale for the scope of clinical treatment. CONCLUSIONS: Considering these premises, it is evident that much detailed translational and clinical studies are needed. Factors such as the length of smoking cessation for ex-smokers, the level of smoke exposure in case of SHS, pre-established health conditions, genetics (and epigenetics modification caused by chronic smoking) are few of the criteria that need to be evaluated to begin assessing the prophylactic and/or therapeutic impact of treatments aimed at chronic and former smokers (especially early stage ex-smokers) including those frequently subjected to second hand tobacco smoke exposure. Herein, we provide a detailed review of health complications and major pathological mechanisms including mutation, inflammation, oxidative stress, and hemodynamic and plasma protein changes associated with chronic smoking. Further, we discuss about prophylactic interventions and associated benefits and provide a rationale and scope for clinical treatment. PMID- 28985717 TI - Identification of VPS35 p.D620N mutation-related Parkinson's disease in a Taiwanese family with successful bilateral subthalamic nucleus deep brain stimulation: a case report and literature review. AB - BACKGROUND: Vacuolar protein sorting 35 (VPS35) was recently reported to be a genetic cause for late-onset autosomal dominant Parkinson's disease (PD). However, VPS35 mutations are rarely reported in Asian populations. Herein, we report the first Taiwanese family with the pathogenic VPS35 p.D620N mutation, including one patient treated successfully with subthalamic nucleus deep brain stimulation (STN-DBS). CASE PRESENTATION: A 61-year-old woman presented with progressive left hand resting tremor at the age of 42. Neurological examinations revealed mask face and akinetic-rigidity over left extremities. She showed a good response to levodopa treatment, and her unified Parkinson's disease rating scale (UPDRS) motor scores improved from 42 to 15 under the levodopa equivalent dose of 1435 mg/day. She developed peak-dose dyskinesia and motor fluctuation seven years after the onset of symptoms, and received bilateral STN-DBS at the age of 55. Stimulation led to a marked improvement in her motor symptoms with a 37% improvement in the UPDRS motor score during the OFF period five years after surgery. The patient's mother and three siblings were also diagnosed with PD in their forties, following an autosomal-dominant inheritance pattern. We performed genetic analysis of the proband using a targeted next generation sequencing (NGS) panel covering 17 known PD-causative genes. We identified a pathogenic missense mutation in VPS35 gene, c.1858G > A (p.D620N), in this patient. CONCLUSIONS: This is the first report of the VPS35 p.D620N mutation in a Taiwanese family. Additionally, our report contributes to the current understanding of genetically defined PD patients treated successfully with STN-DBS. PMID- 28985718 TI - Gender differences in the prevalence of congenital heart disease in Down's syndrome: a brief meta-analysis. AB - BACKGROUND: Down's syndrome (DS) affects one per 700 live births and congenital heart disease (CHD) occurs in 40-60% of these patients. Contributing factors to the association between DS and CHD are being unraveled. Gender could be one of them. METHODS: We performed a meta-analysis of CHD prevalence in DS, separated by gender. Three search engines were used and 578 articles were reviewed. Twelve articles were included. RESULTS: Quantitative analysis showed a higher prevalence of CHD, particularly atrioventricular septal defects (AVSD), in female patients. No differences were found in others forms of CHD. CONCLUSION: CHD, particularly AVSD, are more common in the female gender of Down's syndrome patients. PMID- 28985716 TI - Selection of opioids for cancer-related pain using a biomarker: a randomized, multi-institutional, open-label trial (RELIEF study). AB - BACKGROUND: Cancer patients experience pain that has physiological, sensory, affective, cognitive, behavioral, and sociocultural dimensions. Opioids are used in treatment of pain in patients with various types of cancer. We previously showed that the catechol-O-methyltransferase (COMT) genotype is related to the plasma level of morphine and the required dose of morphine in an exploratory prospective study. The findings showed that a group of patients with a GG single nucleotide polymorphism (SNP) rs4680 in COMT required a significantly higher dose of morphine than a non-GG group. A biomarker for selection of opioids for cancer pain relief would be particularly useful clinically, and therefore we have planned a randomized comparative study of morphine and oxycodone, using the COMT rs4680 SNP as a biomarker. This study is aimed at verifying the assumption that patients in the GG group require an increased morphine dose for pain relief. METHODS: The RELIEF study is a randomized, multi-institutional, open-label trial with a primary endpoint of the proportion of subjects requiring high-dose opioids, as calculated from the dose of a rescue preparation administered on day 0. Secondary endpoints include the Hospital Anxiety and Depression Scale, Short form McGill Pain Questionnaire-2, European Organization for Research and Treatment of Cancer QLQ-C15-PAL, Pain Catastrophizing Scale, and adverse events, Eligibility criteria are patients with advanced carcinoma with non-daily use of opioids in initial screening for registration; and cancer pain targeted for daily opioid treatment, NSAIDs or acetaminophen, NRS >=3(average over 24 h), opioid treatment naive within 30 h, no chemotherapy, radiotherapy, or bisphosphonate administration newly started within 2 weeks, and written informed consent at the time of second registration. Between November 2014 and June 2017, an estimated 110 patients from two sites in Japan were randomized (1:1) to morphine or oxycodone in GG and non-GG groups. DISCUSSION: A method for selection of appropriate opioids in cancer patients is a high unmet medical need. This study was designed to evaluate the efficacy of different opioids in patients with cancer based on gene polymorphism, as the first potential multi-institutional registration trial to be conducted in cancer patients with pain. TRIAL REGISTRATION: UMIN000015579 Date of registration: 4 November 2014. It is updated once every six months, the latest update is 30 June 2017. Trial status. The enrollment started in November 2014. At the time of manuscript submission (July 2017), Three-quarters of patients have participated. We thus expect to complete the recruitment by March 2018. PMID- 28985719 TI - A novel compound mutation in GLRA1 cause hyperekplexia in a Chinese boy- a case report and review of the literature. AB - BACKGROUND: The pathogenesis of hereditary hyperekplexia is thought to involve abnormalities in the glycinergic neurotransmission system, the most of mutations reported in GLRA1. This gene encodes the glycine receptor alpha1 subunit, which has an extracellular domain (ECD) and a transmembrane domain (TMD) with 4 alpha helices (TM1-TM4). CASE PRESENTATION: We investigated the genetic cause of hyperekplexia in a Chinese family with one affected member. Whole-exome sequencing of the 5 candidate genes was performed on the proband patient, and direct sequencing was performed to validate and confirm the detected mutation in other family members. We also review and analyse all reported GLRA1 mutations. The proband had a compound heterozygous GLRA1 mutation that comprised 2 novel GLRA1 missense mutations, C.569C > T (p.T190 M) from the mother and C.1270G > A (p.D424N) from the father. SIFT, Polyphen-2 and MutationTaster analysis identified the mutations as disease-causing, but the parents had no signs of hyperekplexia. The p.T190 M mutation is located in the ECD, while p.D424N is located in TM4. CONCLUSIONS: Our findings contribute to a growing list GLRA1 mutations associated with hyperekplexia and provide new insights into correlations between phenotype and GLRA1 mutations. Some recessive mutations can induce hyperekplexia in combination with other recessive GLRA1 mutations. Mutations in the ECD, TM1, TM1-TM2 loop, TM3, TM3-TM4 loop and TM4 are more often recessive and part of a compound mutation, while those in TM2 and the TM2-TM3 loop are more likely to be dominant hereditary mutations. PMID- 28985720 TI - Effects of Homocysteine on white matter diffusion parameters in Alzheimer's disease. AB - BACKGROUND: The clinical features of Alzheimer's disease (AD) are related to brain network degeneration, and hyperhomocysteinemia is related to greater white matter hyperintensities. We investigated the changes in four diffusion tensor imaging parameters in the white matter of patients with early stage AD, examined their associations with homocysteine level, and tested the clinical significance of the diffusion tensor imaging parameters and homocysteine level in correlation analysis with cognitive test scores. METHODS: We enrolled 132 patients with AD and analyzed white matter (WM) macrostructural changes using diffusion tensor neuroimaging parameters including fractional anisotropy (FA), mean diffusion (MD), axial diffusivity (axial-D) and radial diffusivity (RD). Two neuroimaging post-processing analyses were performed to provide complementary data. First, we calculated 11 major bundle microstructural integrities using a WM parcellation algorithm, and correlated them with serum homocysteine levels to explore whether the fiber bundles were affected by homocysteine. Second, we used tract-based spatial statistics to explore the anatomical regions associated with homocysteine levels. Changes in cognitive test scores caused by homocysteine served as the major outcome factor. RESULTS: The results suggested that homocysteine levels did not have a direct impact on cross-sectional cognitive test scores, but that they were inversely correlated with renal function, B12 and folate levels. Topographies showing independent correlations with homocysteine in FA and MD were more diffusely located compared to the posterior brain regions in axial-D and RD. In the association bundle analysis, homocysteine levels were significantly correlated with the four diffusion parameters even after correcting for confounders, however no association between homocysteine and WM to predict cognitive outcomes was established. CONCLUSIONS: In our patients with AD, homocysteine levels were associated with renal dysfunction and decreased levels of vitamin B12 and folate, all of which require clinical attention as they may have been associated with impaired WM microstructural integrity and modulated cognitive performance in cross-sectional observations. PMID- 28985721 TI - A descriptive pilot study of cytokine production following stimulation of ex-vivo whole blood with commercial therapeutic feline hydrolyzed diets in individual healthy immunotolerant cats. AB - BACKGROUND: Hydrolyzed diets are used in companion animals for the diagnosis and treatment of adverse food reaction. Similarly, hydrolyzed formulas are used in human infants with severe inflammatory bowel disease or milk allergy, and these must meet the standard of hypoallergenicity through rigorous testing. Unfortunately, no standards are currently applied to hydrolyzed veterinary therapeutic diets, and data for the immunogenicity of feline diets is also not available. Therefore, the main aim of this pilot study was to determine if ex vivo whole blood stimulation assays could be used to characterize the cytokine response to hydrolyzed commercial diets in a small number of individual healthy immunotolerant cats. This approach has also been used to investigate cytokine production in response to cow milk protein in humans and currently similar studies do not exist in companion animals. Nine healthy cats previously eating the same basal diet were divided into groups and fed one of three hydrolyzed diets exclusively for 6 weeks. Heparinized whole blood was collected from each cat before and after the feeding trial. Ex-vivo whole blood stimulation assays were performed using crude extracts of the basal diet as a positive control, as this diet contained the same proteins present in the hydrolyzed diet but were intact, saline as a negative control, and each cat's respective hydrolyzed diet. Supernatants were collected and analyzed for tumor necrosis factor-alpha, interleukin-10 (IL-10), and interleukin-4 using enzyme-linked immunosorbant assay. RESULTS: Seven cats produced detectable amounts of the anti-inflammatory cytokine IL-10 upon stimulation with the basal diet. Two cats produced detectable amounts of IL-10 upon stimulation with a hydrolyzed soy-based diet and one cat produced a detectable amount of IL-10 upon stimulation with a hydrolyzed chicken based diet (>125 pg/mL). CONCLUSIONS: Results from this pilot study suggest that in some healthy immunotolerant cats, some hydrolyzed diets may elicit a similar cytokine response compared to their basal diet, which contained the same proteins intact. Therefore, animals may be able to recognize and react to some hydrolyzed forms of tolerated proteins, and may also suggest IL-10 as a target for investigation as a potential marker for dietary tolerance in cats, however further studies would be necessary to corroborate this. Further studies are also needed to determine if this would also be the same in immunologically naive, sensitized and clinically hypersensitized cats. PMID- 28985722 TI - The impact of a referral card-based intervention on intimate partner violence, psychosocial health, help-seeking and safety behaviour during pregnancy and postpartum: a randomized controlled trial. AB - BACKGROUND: We aimed to investigate the impact of a referral-based intervention in a prospective cohort of women disclosing intimate partner violence (IPV) on the prevalence of violence, and associated outcomes psychosocial health, help seeking and safety behaviour during and after pregnancy. METHODS: Women seeking antenatal care in eleven Belgian hospitals were consecutively invited from June 2010 to October 2012, to participate in a single-blind randomized controlled trial (RCT) and handed a questionnaire. Participants willing to be interviewed and reporting IPV victimisation were randomised. In the Intervention Group (IG) participants received a referral card with contact details of services providing assistance and tips to increase safety behaviour. Participants in the Control Group (CG) received a "thank you" card. Follow-up data were obtained through telephone interview at an average of 10 months after receipt of the card. RESULTS: At follow-up (n = 189), 66.7% (n = 126) of the participants reported IPV victimisation. Over the study-period, the prevalence of IPV victimisation decreased by 31.4% (P < 0.001), psychosocial health increased significantly (5.4/140, P < 0.001), 23.8% (n = 46/193) of the women sought formal help, 70.5% (n = 136/193) sought informal help, and 31.3% (n = 60/192) took at least one safety measure. We observed no statistically significant differences between the IG and CG, however. Adjusted for psychosocial health at baseline, the perceived helpfulness of the referral card seemed to be larger in the IG. Both the questionnaire and the interview were perceived to be significantly more helpful than the referral card itself (P < 0.001). CONCLUSIONS: Asking questions can be helpful even for types of IPV of low severity, although simply distributing a referral card may not qualify as the ideal intervention. Future interventions should be multifaceted, delineate different types of violence, controlling for measurement reactivity and designing a tailored intervention programme adjusted to the specific needs of couples experiencing IPV. TRIAL REGISTRATION: The trial was registered with the U.S. National Institutes of Health ClinicalTrials.gov registry on July 6, 2010 under identifier NCT01158690 ). PMID- 28985723 TI - Correction to: Association of plasma potassium with mortality and end-stage kidney disease in patients with chronic kidney disease under nephrologist care - The NephroTest study. PMID- 28985724 TI - Association between dementia and discharge status in patients hospitalized with pneumonia. AB - BACKGROUND: Pneumonia is the most common cause of death in patients with dementia, but the outcomes of patients with dementia hospitalized with pneumonia are poorly understood. We sought to illuminate the association between dementia and in-hospital mortality and discharge status in patients hospitalized with pneumonia. METHODS: We used the Diagnosis Procedure Combination database, a national inpatient database in Japan, to identify retrospectively patients aged >=60 years admitted to hospital with pneumonia during the study period of May 1, 2010 to March 31, 2014. We recorded their sex, age, body mass index, severity of pneumonia and comorbidities (including dementia). The outcomes were in-hospital mortality and discharge home. Multivariable Cox regression analysis was performed to analyze factors influencing discharge home. RESULTS: We identified 470,829 patients hospitalized with pneumonia; 45,031 were recorded as having dementia (9.6%). In-hospital mortality was 13.1% and 13.4% in patients with and without dementia, respectively (P = 0.63). The proportions of patients discharged home were 52.9% and 71.3% in patients with and without dementia, respectively (P < 0.001). The adjusted hazard ratio for discharge home for patients with dementia was 0.68 (95% confidence interval, 0.67-0.69; P < 0.001). CONCLUSIONS: In hospital mortality from pneumonia did not differ significantly between patients with and without dementia; however, those with dementia were less likely to be discharged home. PMID- 28985725 TI - Factors influencing the clinical decision-making of midwives: a qualitative study. AB - BACKGROUND: Although midwives make clinical decisions that have an impact on the health and well-being of mothers and babies, little is known about how they make those decisions. Wide variation in intrapartum decisions to refer women to obstetrician-led care suggests that midwives' decisions are based on more than the evidence based medicine (EBM) model - i.e. clinical evidence, midwife's expertise, and woman's values - alone. With this study we aimed to explore the factors that influence clinical decision-making of midwives who work independently. METHODS: We used a qualitative approach, conducting in-depth interviews with a purposive sample of 11 Dutch primary care midwives. Data collection took place between May and September 2015. The interviews were semi structured, using written vignettes to solicit midwives' clinical decision-making processes (Think Aloud method). We performed thematic analysis on the transcripts. RESULTS: We identified five themes that influenced clinical decision making: the pregnant woman as a whole person, sources of knowledge, the midwife as a whole person, the collaboration between maternity care professionals, and the organisation of care. Regarding the midwife, her decisions were shaped not only by her experience, intuition, and personal circumstances, but also by her attitudes about physiology, woman-centredness, shared decision-making, and collaboration with other professionals. The nature of the local collaboration between maternity care professionals and locally-developed protocols dominated midwives' clinical decision-making. When midwives and obstetricians had different philosophies of care and different practice styles, their collaborative efforts were challenged. CONCLUSION: Midwives' clinical decision-making is a more varied and complex process than the EBM framework suggests. If midwives are to succeed in their role as promoters and protectors of physiological pregnancy and birth, they need to understand how clinical decisions in a multidisciplinary context are actually made. PMID- 28985726 TI - Correction to: Gestational hypertensive disorders and retinal microvasculature: the Generation R Study. PMID- 28985727 TI - Respiratory mechanics in infants with severe bronchiolitis on controlled mechanical ventilation. AB - BACKGROUND: Analysis of respiratory mechanics during mechanical ventilation (MV) is able to estimate resistive, elastic and inertial components of the working pressure of the respiratory system. Our aim was to discriminate the components of the working pressure of the respiratory system in infants on MV with severe bronchiolitis admitted to two PICU's. METHODS: Infants younger than 1 year old with acute respiratory failure caused by severe bronchiolitis underwent neuromuscular blockade, tracheal intubation and volume controlled MV. Shortly after intubation studies of pulmonary mechanics were performed using inspiratory and expiratory breath hold. The maximum inspiratory and expiratory flow (QI and QE) as well as peak inspiratory (PIP), plateau (PPL) and total expiratory pressures (tPEEP) were measured. Inspiratory and expiratory resistances (RawI and RawE) and Time Constants (KTI and KTE) were calculated. RESULTS: We included 16 patients, of median age 2.5 (1-5.8) months. Bronchiolitis due to respiratory syncytial virus was the main etiology (93.8%) and 31.3% had comorbidities. Measured respiratory pressures were PIP 29 (26-31), PPL 24 (20-26), tPEEP 9 [8 11] cmH2O. Elastic component of the working pressure was significantly higher than resistive and both higher than threshold (tPEEP - PEEP) (P < 0.01). QI was significantly lower than QE [5 (4.27-6.75) v/s 16.5 (12-23.8) L/min. RawI and RawE were 38.8 (32-53) and 40.5 (22-55) cmH2O/L/s; KTI and KTE [0.18 (0.12-0.30) v/s 0.18 (0.13-0.22) s], and KTI:KTE ratio was 1:1.04 (1:0.59-1.42). CONCLUSIONS: Analysis of respiratory mechanics of infants with severe bronchiolitis receiving MV shows that the elastic component of the working pressure of the respiratory system is the most important. The elastic and resistive components in conjunction with flow profile are characteristic of restrictive diseases. A better understanding of lung mechanics in this group of patients may lead to change the traditional ventilatory approach to severe bronchiolitis. PMID- 28985728 TI - Outcomes identified and prioritised by consumers of Partners in Recovery: a consumer-led study. AB - BACKGROUND: Recovery oriented service provisions means focusing on outcomes that are important to consumers themselves rather than to clinicians or services. Partners in Recovery (PIR) is an Australia-wide initiative designed to provide service coordination and brokerage for individuals with severe and persistent mental illness. One PIR service engaged a consumer-led research team to evaluate the service from the perspective of consumers. This consumer-led study was established to explore PIR consumers' perceptions of outcomes they achieved through their involvement with PIR. METHODS: Data were collected through semi structured interviews exploring participants' views about and experiences with PIR. Data analysis occurred simultaneously with data collection using constant comparative analysis. RESULTS: Twenty consumers participated. They reported experiencing valued outcomes in six domains: feeling supported; feeling more hopeful and positive about the future; improved mental clarity, focus and order in life; getting out of the house and engaging in positive activity; having a better social life; and improved physical health. CONCLUSIONS: Exploring outcomes achieved by PIR consumers, from their own perspective provides a nuanced understanding of the contribution these programs can have in supporting individuals' recovery. Findings from this study highlight the kinds of outcomes consumers achieve when engaged with service coordination and brokerage services. Findings also suggest that outcome measures used in these types of services should focus on recovery outcomes as well as met and unmet needs. PMID- 28985729 TI - A novel bedside cardiopulmonary physical diagnosis curriculum for internal medicine postgraduate training. AB - BACKGROUND: Physicians spend less time at the bedside in the modern hospital setting which has contributed to a decline in physical diagnosis, and in particular, cardiopulmonary examination skills. This trend may be a source of diagnostic error and threatens to erode the patient-physician relationship. We created a new bedside cardiopulmonary physical diagnosis curriculum and assessed its effects on post-graduate year-1 (PGY-1; interns) attitudes, confidence and skill. METHODS: One hundred five internal medicine interns in a large U.S. internal medicine residency program participated in the Advancing Bedside Cardiopulmonary Examination Skills (ACE) curriculum while rotating on a general medicine inpatient service between 2015 and 2017. Teaching sessions included exam demonstrations using healthy volunteers and real patients, imaging didactics, computer learning/high-fidelity simulation, and bedside teaching with experienced clinicians. Primary outcomes were attitudes, confidence and skill in the cardiopulmonary physical exam as determined by a self-assessment survey, and a validated online cardiovascular examination (CE). RESULTS: Interns who participated in ACE (ACE interns) by mid-year more strongly agreed they had received adequate training in the cardiopulmonary exam compared with non-ACE interns. ACE interns were more confident than non-ACE interns in performing a cardiac exam, assessing the jugular venous pressure, distinguishing 'a' from 'v' waves, and classifying systolic murmurs as crescendo-decrescendo or holosystolic. Only ACE interns had a significant improvement in score on the mid-year CE. CONCLUSIONS: A comprehensive bedside cardiopulmonary physical diagnosis curriculum improved trainee attitudes, confidence and skill in the cardiopulmonary examination. These results provide an opportunity to re-examine the way physical examination is taught and assessed in residency training programs. PMID- 28985730 TI - Clinical utility of the low-density Infinium QC genotyping Array in a genomics based diagnostics laboratory. AB - BACKGROUND: With 15,949 markers, the low-density Infinium QC Array-24 BeadChip enables linkage analysis, HLA haplotyping, fingerprinting, ethnicity determination, mitochondrial genome variations, blood groups and pharmacogenomics. It represents an attractive independent QC option for NGS-based diagnostic laboratories, and provides cost-efficient means for determining gender, ethnic ancestry, and sample kinships, that are important for data interpretation of NGS-based genetic tests. METHODS: We evaluated accuracy and reproducibility of Infinium QC genotyping calls by comparing them with genotyping data of the same samples from other genotyping platforms, whole genome/exome sequencing. Accuracy and robustness of determining gender, provenance, and kinships were assessed. RESULTS: Concordance of genotype calls between Infinium QC and other platforms was above 99%. Here we show that the chip's ancestry informative markers are sufficient for ethnicity determination at continental and sometimes subcontinental levels, with assignment accuracy varying with the coverage for a particular region and ethnic groups. Mean accuracies of provenance prediction at a regional level were varied from 81% for Asia, to 89% for Americas, 86% for Africa, 97% for Oceania, 98% for Europe, and 100% for India. Mean accuracy of ethnicity assignment predictions was 63%. Pairwise concordances of AFR samples with the samples from any other super populations were the lowest (0.39-0.43), while the concordances within the same population were relatively high (0.55-0.61). For all populations except African, cross-population comparisons were similar in their concordance ranges to the range of within population concordances (0.54-0.57). Gender determination was correct in all tested cases. CONCLUSIONS: Our results indicate that the Infinium QC Array-24 chip is suitable for cost-efficient, independent QC assaying in the settings of an NGS-based molecular diagnostic laboratory; hence, we recommend its integration into the standard laboratory workflow. Low-density chips can provide sample specific measures for variant call accuracy, prevent sample mix-ups, validate self-reported ethnicities, and detect consanguineous cases. Integration of low density chips into QC procedures aids proper interpretation of candidate sequence variants. To enhance utility of this low-density chip, we recommend expansion of ADME and mitochondrial markers. Inexpensive Infinium-like low-density human chips have a potential to become a "Swiss army knife" among genotyping assays suitable for many applications requiring high-throughput assays. PMID- 28985731 TI - Screening for celiac disease in poorly controlled type 2 diabetes mellitus: worth it or not? AB - BACKGROUND: Recent studies have demonstrated that immune factors might have a role in the pathophysiology of insulin resistance and type 2 diabetes mellitus (T2DM). Inappropriate glycemic control in patients with T2DM is an important risk factor for the occurrence of diabetes complications. The prevalence of celiac disease (CD) is high in type 1 diabetes mellitus however, there are scarce data about its prevalence in T2DM. Our aim was to investigate the prevalence of celiac disease among insulin-using type 2 diabetes patients with inappropriate glycemic control. METHODS: IgA tissue transglutaminase antibodies (tTGA IgA) test was performed as a screening test. A total of 135 patients with T2DM whose control of glycemia is inappropriate (HbAlc value >7%) in spite of using insulin treatment for at least 3-months (only insulin or insulin with oral antidiabetic drugs) and 115 healthy controls were enrolled in the study. Upper gastrointestinal endoscopy with duodenal biopsy was performed to all patients with raised tTGA IgA or selective lgA deficiency. RESULTS: Gender, age, body mass index (BMI) and tTGA IgA, kreatinin, calcium, LDL-cholesterol (LDL-C), total cholesterol, 25-OH vitamin D3 levels were similar between groups. Systolic and diastolic blood pressure, waist circumference, fasting plasma glucose, postprandial plasma glucose, urea, sodium, HbA1c, LDL-C, triglyceride, vitamin B12 levels were significantly higher in DM group (p < 0.0001). BMI, high-sensitive CRP, microalbuminuria, and AST, ALT, potassium, phosphorus levels were significantly higher in the T2DM group (p < 0.05). HDL-cholesterol and parathormone levels were significantly lower in the T2DM group (p < 0.05). Two of the 135 patients with T2DM were diagnosed with CD (1.45%). CONCLUSIONS: The prevalence of celiac disease among patients with type 2 diabetes, with poor glycemic control despite insulin therapy, is slightly higher than the actual CD prevalence in general population. Type 2 diabetic patients with inappropriate control of glycemia in spite of insulin treatment might be additionally tested for Celiac disease especially if they have low C-peptide levels. PMID- 28985732 TI - Cost-effectiveness of malaria preventive treatment for HIV-infected pregnant women in sub-Saharan Africa. AB - BACKGROUND: Malaria is a leading cause of morbidity and mortality among HIV infected pregnant women in sub-Saharan Africa: at least 1 million pregnancies among HIV-infected women are complicated by co-infection with malaria annually, leading to increased risk of premature delivery, severe anaemia, delivery of low birth weight infants, and maternal death. Current guidelines recommend either daily cotrimoxazole (CTX) or intermittent preventive treatment with sulfadoxine pyrimethamine (IPTp-SP) for HIV-infected pregnant women to prevent malaria and its complications. The cost-effectiveness of CTX compared to IPTp-SP among HIV infected pregnant women was assessed. METHODS: A microsimulation model of malaria and HIV among pregnant women in five malaria-endemic countries in sub-Saharan Africa was constructed. Four strategies were compared: (1) 2-dose IPTp-SP at current IPTp-SP coverage of the country ("2-IPT Low"); (2) 3-dose IPTp-SP at current coverage ("3-IPT Low"); (3) 3-dose IPTp-SP at the same coverage as antiretroviral therapy (ART) in the country ("3-IPT High"); and (4) daily CTX at ART coverage. Outcomes measured include maternal malaria, anaemia, low birth weight (LBW), and disability-adjusted life years (DALYs). Sensitivity analyses assessed the effect of adherence to CTX. RESULTS: Compared with the 2-IPT Low Strategy, women receiving CTX had 22.5% fewer LBW infants (95% CI 22.3-22.7), 13.5% fewer anaemia cases (95% CI 13.4-13.5), and 13.6% fewer maternal malaria cases (95% CI 13.6-13.7). In all simulated countries, CTX was the preferred strategy, with incremental cost-effectiveness ratios ranging from cost-saving to $3.9 per DALY averted from a societal perspective. CTX was less effective than the 3-IPT High Strategy when more than 18% of women stopped taking CTX during the pregnancy. CONCLUSION: In malarious regions of sub-Saharan Africa, daily CTX for HIV-infected pregnant women regardless of CD4 cell count is cost-effective compared with 3-dose IPTp-SP as long as more than 82% of women adhere to daily dosing. PMID- 28985733 TI - Topical use of 5% acyclovir cream for the treatment of occult and verrucous equine sarcoids: a double-blinded placebo-controlled study. AB - BACKGROUND: Previous studies mention the use of topical acyclovir for the treatment of equine sarcoids. Success rates vary and since the bovine papillomavirus (BPV) lacks the presence of a kinase necessary to activate acyclovir, there is no proof of its activity against equine sarcoids. RESULTS: Twenty-four equine sarcoids were topically treated with acyclovir cream and 25 with a placebo. Both creams were applied twice daily during 6 months. Before the start of the treatment and further on a monthly basis, photographs and swabs were obtained. On the photographs, sarcoid diameter and surface area were measured and verrucosity of the tumours was quantified using a visual analog scale (VAS). The swabs were analysed by PCR for the presence of BPV DNA and positivity rates were calculated as the number of positive swabs divided by the total number of swabs for each treatment group at each time point. Success rates were not significantly different between both treatment groups. There was also no significant effect of treatment on sarcoid diameter, surface area or VAS score. For the swabs, a significantly higher BPV positivity rate was found for acyclovir treated tumours compared to placebo treated sarcoids only after 1 month of treatment and not at other time points. CONCLUSIONS: None of the results indicate that treatment with acyclovir yields any better results compared to placebo treatment. PMID- 28985734 TI - Individual and household factors associated with ownership of long-lasting insecticidal nets and malaria infection in south-central Ethiopia: a case-control study. AB - BACKGROUND: A recent considerable decline in malaria morbidity and mortality in Ethiopia is likely to be followed by changes in the practice of effective preventive measures and malaria risk factors. This study aimed to identify determinants of long-lasting insecticidal nets (LLINs) ownership and risk of malaria infection. METHODS: A matched case-control study of 191 case and 377 control households was conducted between October 2014 and November 2015 in Adami Tullu district in south-central Ethiopia. Cases were microscopy or rapid diagnostic test confirmed malaria patients identified at three health centers and nine health posts, and matched on age with two neighbourhood controls. Information was collected on socio-demographic factors, house structure, knowledge on malaria and ownership of LLINs. The logistic regression model was used to determine predictors of LLINs ownership and malaria infection. RESULTS: All cases were infections due to either Plasmodium falciparum (71.2%) or Plasmodium vivax (28.8%). About 31% of the study households had at least one LLINs. Significant determinants of LLINs ownership were household's head malaria knowledge [adjusted odds ratio (AOR) = 2.47, 95% confidence interval (CI) 1.44 4.22], educational status [read and write (AOR = 6.88, 95% CI 2.30-20.55), primary education or higher (AOR = 5.40, 95% CI 1.57-18.55)], farmer respondent (AOR = 0.35, 95% CI 0.17-0.76), having >= 3 sleeping areas (AOR = 6.71, 95% CI 2.40-18.77) and corrugated roof type (AOR = 2.49, 95% CI 1.36-4.58). This study was unable to identify important risk factors of malaria infection with regard to sex, household wealth index, house structure, ownership of LLINs, keeping livestock inside house, staying overnight outdoor or having malaria during the last 6 months. CONCLUSIONS: Household socio-economic status, educational status and knowledge on malaria were important predictors of LLINs ownership. Households with farmer respondents were less likely to own LLINs. Addressing these factors could improve household's ownership of LLINs. The importance of factors associated with malaria infection was less evident in the current low transmission setting, and necessitates further epidemiological study. PMID- 28985735 TI - Objective and subjective diagnostic parameters in the fellow eye of unilateral keratoconus. AB - BACKGROUND: Keratoconus (KC) is usually a bilateral corneal ectatic disease. For significant asymmetric presentation (so called unilateral KC), the fellow eye has the mildest and earliest form of the disease, which is typically called forme fruste keratoconus. The aim of this study was to evaluate the sensitivity and specificity of parameters derived from a Scheimpflug imaging system (Pentacam) as well as the changes in the quality of mesopic vision in the apparently normal fellow eye (forme fruste) to detect the earliest and most sensitive parameters. METHODS: Patients with clinical keratoconus in one eye and forme fruste keratoconus in the fellow eye were compared to subjects with normal eyes. The patients were examined using a rotating Scheimpflug imaging system (Pentacam).The following parameters were evaluated: keratometry, minimum corneal thickness, pachymetry progression index (PPI), Ambrosio relational thickness (ART), posterior elevation, back difference elevation (BDE) and multimetric D index(D index). Receiver operating characteristic (ROC) curves were analyzed by evaluating the area under the curve (AUC) to detect the sensitivity and specificity of each parameter. Mesopic vision evaluations were performed by contrast sensitivity and glare tests for each group. RESULTS: A total of 48 patients with clinical keratoconus in one eye and forme fruste keratoconus in the fellow eye and 72normal subjects were evaluated. In the clinical keratoconus eyes, the mean K, back difference elevation (BDE), pachymetric progression index maximum(PPI max), and multimetric D were significantly higher compared to the normal subjects, whereas the corneal pachymetry and Ambrosio relational thickness maximum (ART max) were significantly lower. In the forme fruste eyes, the ROC analysis showed that the AUC values of the mean K, thinnest pachymetry, ARTmax, BDE, D index, and PPI max were 0.82, 0.61, 0.88, 0. 67, and 0.64, respectively. The contrast sensitivity and glare tests were significantly affected in the forme fruste cases. CONCLUSION: In forme fruste keratoconus eyes, the ART max is considered a highly sensitive objective parameter. Contrast sensitivity and glare is an important subjective test, which is affected in forme fruste patients. PMID- 28985736 TI - Spatial clustering of fatal, and non-fatal, suicide in new South Wales, Australia: implications for evidence-based prevention. AB - BACKGROUND: Rates of suicide appear to be increasing, indicating a critical need for more effective prevention initiatives. To increase the efficacy of future prevention initiatives, we examined the spatial distribution of suicide deaths and suicide attempts in New South Wales (NSW), Australia, to identify where high incidence 'suicide clusters' were occurring. Such clusters represent candidate regions where intervention is critically needed, and likely to have the greatest impact, thus providing an evidence-base for the targeted prioritisation of resources. METHODS: Analysis is based on official suicide mortality statistics for NSW, provided by the Australian Bureau of Statistics, and hospital separations for non-fatal intentional self-harm, provided through the NSW Health Admitted Patient Data Collection at a Statistical Area 2 (SA2) geography. Geographical Information System (GIS) techniques were applied to detect suicide clusters occurring between 2005 and 2013 (aggregated), for persons aged over 5 years. The final dataset contained 5466 mortality and 86,017 non-fatal intentional self-harm cases. RESULTS: In total, 25 Local Government Areas were identified as primary or secondary likely candidate regions for intervention. Together, these regions contained approximately 200 SA2 level suicide clusters, which represented 46% (n = 39,869) of hospital separations and 43% (n = 2330) of suicide deaths between 2005 and 2013. These clusters primarily converged on the Eastern coastal fringe of NSW. CONCLUSIONS: Crude rates of suicide deaths and intentional self-harm differed at the Local Government Areas (LGA) level in NSW. There was a tendency for primary suicide clusters to occur within metropolitan and coastal regions, rather than rural areas. The findings demonstrate the importance of taking geographical variation of suicidal behaviour into account, prior to development and implementation of prevention initiatives, so that such initiatives can target key problem areas where they are likely to have maximal impact. PMID- 28985737 TI - RNA sequencing identifies novel non-coding RNA and exon-specific effects associated with cigarette smoking. AB - BACKGROUND: Cigarette smoking is the leading modifiable risk factor for disease and death worldwide. Previous studies quantifying gene-level expression have documented the effect of smoking on mRNA levels. Using RNA sequencing, it is possible to analyze the impact of smoking on complex regulatory phenomena (e.g. alternative splicing, differential isoform usage) leading to a more detailed understanding of the biology underlying smoking-related disease. METHODS: We used whole-blood RNA sequencing to describe gene and exon-level expression differences between 229 current and 286 former smokers in the COPDGene study. We performed differential gene expression and differential exon usage analyses using the voom/limma and DEXseq R packages. Samples from current and former smokers were compared while controlling for age, gender, race, lifetime smoke exposure, cell counts, and technical covariates. RESULTS: At an adjusted p-value <0.05, 171 genes were differentially expressed between current and former smokers. Differentially expressed genes included 7 long non-coding RNAs that have not been previously associated with smoking: LINC00599, LINC01362, LINC00824, LINC01624, RP11-563D10.1, RP11-98G13.1, AC004791.2. Secondary analysis of acute smoking (having smoked within 2-h) revealed 5 of the 171 smoking genes demonstrated an acute response above the baseline effect of chronic smoking. Exon-level analyses identified 9 exons from 8 genes with significant differential usage by smoking status, suggesting smoking-induced changes in isoform expression. CONCLUSIONS: Transcriptomic changes at the gene and exon levels from whole blood can refine our understanding of the molecular mechanisms underlying the response to smoking. PMID- 28985738 TI - Mitigating risks of students use of study drugs through understanding motivations for use and applying harm reduction theory: a literature review. AB - As postsecondary students' use of "study drugs" becomes more popular with increasingly reported negative effects on health and academic performance, failing prohibitionist policies to reduce consumption, and ambiguity in literature towards best practices to address this population, we present a literature review that seeks effective solutions educational institutions can apply to improve outcomes for students who use drugs. Motivations for use, effects of the substances, an analysis of efforts to control use from educational institutions, and suggestions on promoting most effective outcomes based on harm reduction, are described. Theory, quantitative, and qualitative works from systematic reviews, cohort studies, and epidemiological assessments are examined on the "study drugs" methylphenidate, dextroamphetamine, and amphetamine, also known as Adderall, Ritalin, Focalin, and Concerta. There is a focus on postsecondary students ages 18-25 in North America. Results show important risk factors for drug use including low perceived self-efficacy or enjoyment in courses, poor accommodation of special needs, reliance on external validation, having a low GPA, and experiencing a mental health issue. There is much misconception on the health and academic effects of these drugs in literature, among students, and on online knowledge sources. We suggest these drugs do not improve GPA and learning, while they might temporarily increase memory, but with detrimental negative health effects. Campaigns that address underlying factors of use can be most successful in mitigating harms. PMID- 28985739 TI - A lipidated peptide of Mycobacterium tuberculosis resuscitates the protective efficacy of BCG vaccine by evoking memory T cell immunity. AB - BACKGROUND: The current BCG vaccine induces only short-term protection against Mycobacterium tuberculosis (Mtb), suggesting its failure to generate long-lasting memory T cells. Previously, we have demonstrated that a self-adjuvanting peptide of Mtb (L91), successfully generated enduring memory Th1 cells. Consequently, we investigated if L91 was able to recuperate BCG potency in perpetuating the generation of memory T cells and protection against Mtb infected mice. METHODS: In the present study, we evaluated the potency of a self adjuvanting Mtb peptide vaccine L91 in invigorating BCG immune response against Mtb in mice. Female BALB/c mice were immunized with BCG. Later, they were boosted twice with L91 or an antigenically irrelevant lipidated influenza virus hemagglutinin peptide (LH). Further, PBMCs obtained from BCG vaccinated healthy subjects were cultured in vitro with L91. T cell responses were determined by surface markers and intracellular cytokine staining. Secretion of cytokines was estimated in the culture supernatants (SNs) by ELISA. RESULTS: Compared to the BCG-vaccinated controls, L91 booster significantly enhanced the percentage of memory Th1 cells and Th17 cells and reduced the mycobacterial burden in BCG primed and L91-boosted (BCG-L91) group, even after 229 days of BCG vaccination. Further, substantial augmentation in the central (CD44hiCD62LhiCD127hi) and effector memory (CD44hiCD62LloCD127lo) CD4 T cells was detected. Furthermore, greater frequency of polyfunctional Th1 cells (IFN-gamma+TNF-alpha+) and Th17 cells (IFN-gamma+IL 17A+) was observed. Importantly, BCG-L91 successfully prevented CD4 T cells from exhaustion by decreasing the expression of PD-1 and Tim-3. Additionally, augmentation in the frequency of Th1 cells, Th17 cells and memory CD4 T cells was observed in the PBMCs of the BCG-vaccinated healthy individuals following in vitro stimulation with L91. CONCLUSIONS: Our study demonstrated that L91 robustly reinvigorate BCG potency to invoke enduring protection against Mtb. This novel vaccination stratagem involving BCG-priming followed by L91-boosting can be a future prophylactic measure to control TB. PMID- 28985740 TI - Nanoscale click-reactive scaffolds from peptide self-assembly. AB - BACKGROUND: Due to their natural tendency to self-assemble, proteins and peptides are important components for organic nanotechnology. One particular class of peptides of recent interest is those that form amyloid fibrils, as this self assembly results in extremely strong, stable quasi-one-dimensional structures which can be used to organise a wide range of cargo species including proteins and oligonucleotides. However, assembly of peptides already conjugated to proteins is limited to cargo species that do not interfere sterically with the assembly process or misfold under the harsh conditions often used for assembly. Therefore, a general method is needed to conjugate proteins and other molecules to amyloid fibrils after the fibrils have self-assembled. RESULTS: Here we have designed an amyloidogenic peptide based on the TTR105-115 fragment of transthyretin to form fibrils that display an alkyne functionality, important for bioorthogonal chemical reactions, on their surface. The fibrils were formed and reacted both with an azide-containing amino acid and with an azide-functionalised dye by the Huisgen cycloaddition, one of the class of "click" reactions. Mass spectrometry and total internal reflection fluorescence optical microscopy were used to show that peptides incorporated into the fibrils reacted with the azide while maintaining the structure of the fibril. These click-functionalised amyloid fibrils have a variety of potential uses in materials and as scaffolds for bionanotechnology. DISCUSSION: Although previous studies have produced peptides that can both form amyloid fibrils and undergo "click"-type reactions, this is the first example of amyloid fibrils that can undergo such a reaction after they have been formed. Our approach has the advantage that self-assembly takes place before click functionalization rather than pre-functionalised building blocks self-assembling. Therefore, the molecules used to functionalise the fibril do not themselves have to be exposed to harsh, amyloid-forming conditions. This means that a wider range of proteins can be used as ligands in this process. For instance, the fibrils can be functionalised with a green fluorescent protein that retains its fluorescence after it is attached to the fibrils, whereas this protein loses its fluorescence if it is exposed to the conditions used for aggregation. PMID- 28985741 TI - Lack of efficacy of pomegranate supplementation for glucose management, insulin levels and sensitivity: evidence from a systematic review and meta-analysis. AB - BACKGROUND: The potential glucose-lowering effects of pomegranate have been reported in animal and observational studies, but intervention studies in humans have generated mixed results. In this paper, we aimed to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the precise effects of pomegranate supplementation on measures of glucose control, insulin levels and insulin sensitivity in humans. METHODS: Comprehensive electronic searches were conducted in PubMed, Embase, and the Cochrane Library. Studies included were RCTs that evaluated the changes in diabetes biomarkers among adults (>=18 years) following pomegranate interventions. The predefined outcomes included fasting blood glucose (FBG), fasting blood insulin (FBI), glycated haemoglobin (HbA1c), and homeostatic model assessment of insulin resistance (HOMA-IR). Endpoints were calculated as weighted mean differences (WMDs) with 95% confidence intervals (CIs) by using a random-effects model. Publication bias, subgroup analyses, sensitivity analysis and random-effects meta regression were also performed to explore the influence of covariates on the net changes in fasting glucose and insulin concentrations. RESULTS: Sixteen eligible trials with 538 subjects were included. The pooled estimates suggested that pomegranate did not significantly affect the measures of FBG (WMD, -0.6 mg/dL; 95% CI, -2.79 to 1.58; P=0.59), FBI (WMD, 0.29 MUIU/mL; 95% CI, -1.16 to 1.75; P=0.70), HOMA-IR (WMD, -0.04; 95% CI, -0.53 to 0.46; P=0.88) or HbA1c (WMD, 0.11%; 95% CI, -0.39 to -0.18; P=0.46). Overall, significant heterogeneity was detected for FBI and HOMA-IR, but subgroup analysis could not identify factors significantly influencing these parameters. These results were robust in sensitivity analysis, and no significant publication bias was found in the current meta-analysis. CONCLUSION: Pomegranate intake did not show a notably favourable effect on improvements in glucose and insulin metabolism. The current evidence suggests that daily pomegranate supplementation is not recommended as a potential therapeutic strategy in glycemic management. Further large-scale RCTs with longer duration are required to confirm these results. PMID- 28985742 TI - Health-related quality of life in children with congenital adrenal hyperplasia. AB - BACKGROUND: Children with congenital adrenal hyperplasia (CAH) require life-long glucocorticoid replacement and have daily intermittent hyper/hypocortisolemia and hyperandrogenemia. Health-related quality of life (HRQL) is important for understanding the impact the disease and therapy have on physical, mental, emotional, and social functioning. Little is known about HRQL in CAH. We compared HRQL in children with CAH to healthy norms and examined how these scores related to physiologic variables. METHODS: A cross-sectional study examined 45 patients (mean age 8.2(4.5) years). Thirty-two self-reported their quality of life (QoL) on the PedsQLTM Generic Core Scale and PedsQLTM Fatigue Scale, and 44 parents completed a parent report. Bone age Z-scores were calculated from the most recent bone age. RESULTS: Children with CAH did not report lower QoL than healthy norms. However, their parents reported lower overall QoL and fatigue scores than parents of healthy norms. Children with CAH rated sleep poorer than their parents. QoL scores did not differ by sex or CAH subtype and were not associated with total daily hydrocortisone dose. Bone age Z-scores were negatively associated with child-reported emotional health and cognitive fatigue. CONCLUSIONS: Parents of children with CAH reported a negative impact of disease on their children's QoL, but their children did not. The negative associations between bone age Z-scores and emotional health and cognitive fatigue suggest an impact from chronic hypocortisolemia and hyperandrogenemia. PMID- 28985743 TI - Efficacy of functional foods mixture in improving hypercholesterolemia, inflammatory and endothelial dysfunction biomarkers-induced by high cholesterol diet. AB - BACKGROUND: Hypercholesterolemia associated with cardiovascular diseases is a global health issue that could be alleviated by functional foods. This study aimed to explore the effects of a high-cholesterol diet on lipid profile, cardiac, inflammatory, and endothelial dysfunction biomarkers, and the possible improvement by functional foods mixture. METHODS: Male albino rats weighing 100 150 g were randomly divided into four equal groups: 1st control, giving a normal diet; the 2nd received high-cholesterol diet for 8 weeks, the 3rd received the high-cholesterol diet + functional foods mixture, and the 4th administered high cholesterol diet +atorvastatin (20 mg) orally. RESULTS: The results showed a significant increase in lipid profile and cardiac biomarkers levels (lactate dehydrogenase, creatine kinase and homocystein), also inflammatory markers, as, tumor necrotic factor alpha and chronic reactive proteins were elevated, moreover, vascular adhesion molecule-1 and nitric oxide synthase were disturbed in high-cholesterol diet compared with normal group. While administration of atorvastatin and functional foods mixture ameliorated these alterations. CONCLUSIONS: Administration of functional foods mixture and atorvastatin were effective in treating hypercholesterolemia, reduce the risk of inflammation and cardiovascular biomarkers with a high safety margin. These efficiencies may be due to its active ingredient that improve the imbalance in the measured biomarkers. PMID- 28985744 TI - Correction to: ReMixT: clone-specific genomic structure estimation in cancer. PMID- 28985746 TI - Porcine model of progressive cardiac hypertrophy and fibrosis with secondary postcapillary pulmonary hypertension. AB - BACKGROUND: Meaningful translational large animal models for cardiac diseases are indispensable for studying disease mechanisms, development of novel therapeutic strategies, and evaluation of potential drugs. METHODS: For induction of heart failure, cardiac hypertrophy and fibrosis, a bare metal stent was implanted in the descending aorta of growing pigs (n = 7), inducing pressure stress on the left ventricle (group HYPI). The constant stent size in growing pigs resulted in antegrade partial obstruction of the aortic flow with a gradual increase in afterload. Five pigs with sham intervention served as control. Serial haemodynamic, pressure-volume loop measurements and transthoracic echocardiography (TTE) were performed to detect developing pressure overload of the LV and cardiac MRI with late enhancement for measuring LV and RV mass and ejection fraction. RESULTS: At 5-month follow-up, CT and contrast aortography, and intraluminal echocardiography confirmed aortic isthmus stenosis with a mean trans-stenotic gradient of 64 +/- 13.9 mmHg. Invasive haemodynamic measurements revealed a secondary increase in pulmonary artery pressure (44.6 +/- 5.1 vs 25.9 +/- 6.2 mmHg, HYPI vs control, p < 0.05). TTE and ex vivo analyses confirmed severe concentric LV hypertrophy (mean circumferential wall thickness, 19.4 +/- 3.1, n = 7 vs 11.4 +/- 1.0 mm, n = 5, HYPI vs controls, p < 0.05). The LV and RV mass increased significantly, paralleled by increased isovolumic relaxation constant (tau). Histological analyses confirmed substantial fibrosis and myocyte hypertrophy in both LV and RV. Expressions of ANP, BNP, and miRNA-29a were up regulated, while SERCA2a and miRNA-1 were down-regulated. Plasma NGAL levels increased gradually, while the elevation of NT-proBNP was detected only at the 5 month FUP. CONCLUSION: These data prove that percutaneous artificial aortic stenosis in pigs is useful for inducing clinically relevant progredient heart failure based on myocardial hypertrophy and fibrosis. PMID- 28985747 TI - Thyroid hemiagenesis and Hashimoto's thyroditis-diagnostic and treatment pitfalls. AB - BACKGROUND: Thyroid hemiagenesis (TH) is a rare congenital disease with absence of a thyroid lobe; most patients have no clinical symptoms. The etiology of TH remains unclear. In this paper, we describe a rare case of TH and congenital absence of the ipsilateral parathyroid gland, found during the operation, combined with the autoimmune disease Hashimoto's thyroiditis, also known as chronic lymphocytic thyroiditis. CASE PRESENTATION: A 31-year-old woman was admitted to our hospital because of a mass in the right neck. Surgical exploration validated the absence of the left lobe of the thyroid and parathyroid glands, and pathological examination of the excised nodules confirmed Hashimoto's thyroiditis. Patients with TH might show accompanying absence of the ipsilateral parathyroid gland. The case described here, in which TH was combined with Hashimoto's thyroiditis, is rare in the medical literature. The operation should be ended at once if Hashimoto's thyroiditis is diagnosed during surgery. CONCLUSIONS: Absence of thyroid lobe may accompany with a congenital absence of the ipsilateral parathyroid gland and Hashimoto's thyroiditis. Fine needle aspiration is essential to diagnosis and decision-making of the treatment. PMID- 28985748 TI - Correction to: Trends in use of and complications from intrauterine contraceptive devices and tubal ligation or occlusion. PMID- 28985745 TI - Mucus and Mucins: do they have a role in the inhibition of the human immunodeficiency virus? AB - BACKGROUND: Mucins are large O-linked glycosylated proteins which give mucus their gel-forming properties. There are indications that mucus and mucins in saliva, breast milk and in the cervical plug inhibit the human immunodeficiency virus (HIV-1) in an in vitro assay. Crude mucus gels form continuous layers on the epithelial surfaces of the major internal tracts of the body and protect these epithelial surfaces against aggressive luminal factors such as hydrochloric acid and pepsin proteolysis in the stomach lumen, the movement of hard faecal pellets in the colon at high pressure, the effects of shear against the vaginal epithelium during intercourse and the presence of foreign substances in the respiratory airways. Tumour-associated epitopes on mucins make them suitable as immune-targets on malignant epithelial cells, rendering mucins important as diagnostic and prognostic markers for various diseases, even influencing the design of mucin-based vaccines. Sub-Saharan Africa has the highest prevalence of HIV-AIDS in the world. The main points of viral transmission are via the vaginal epithelium during sexual intercourse and mother-to-child transmission during breast-feeding. There have been many studies showing that several body fluids have components that prevent the transmission of HIV-1 from infected to non infected persons through various forms of contact. Crude saliva and its purified mucins, MUC5B and MUC7, and the purified mucins from breast milk, MUC1 and MUC4 and pregnancy plug cervical mucus (MUC2, MUC5AC, MUC5B and MUC6), inhibit HIV-1 in an in vitro assay. There are conflicting reports of whether crude breast-milk inhibits HIV-1 in an in vitro assay. However studies with a humanised BLT mouse show that breast-milk does inhibit HIV and that breast-feeding is still advisable even amongst HIV-positive women in under-resourced areas, preferably in conjunction with anti-retroviral treatment. CONCLUSION: These findings raise questions of how such a naturally occurring biological substance such as mucus, with remarkable protective properties of epithelial surfaces against aggressive luminal factors in delicate locations, could be used as a tool in the fight against HIV-AIDS, which has reached epidemic proportions in sub-Saharan Africa. PMID- 28985749 TI - Correction to: Leucine-Rich Repeat Kinase 2 (LRRK2) phosphorylates p53 and induces p21WAF1/CIP1 expression. PMID- 28985751 TI - Assessment of the kinesiotherapy's efficacy in male athletes with calcaneal apophysitis. AB - BACKGROUND: The aim of the present study was to assess the efficacy of kinesiotherapy used for treating various disorders in athletes on pain and pedal functions in patients with calcaneal apophysitis. METHODS: This prospective randomized controlled study included 22 patients with calcaneal apophysitis aged 8 to 16 years presenting with heel pain among junior athletes of a professional football club. The patients were randomly grouped into two groups, with one group receiving sham tape only and the other kinesio tape. American Orthopedic Foot & Ankle Society (AOFAS) and visual analog scale (VAS) scores were recorded before and after the treatment. RESULTS: The preoperative VAS score of the kinesio tape was 7, and AOFAS score was 62.4; the corresponding figures of the sham group were 6.81 and 70.5, respectively. The kinesio-tape group had a better AOFAS scores at 1st and 3rd month (p < 0.05). Posttreatment AOFAS score was 99.7 +/- 0.9 for the kinesio-tape group and 97.4 +/- 3.9 for the sham-tape group. Posttreatment VAS score was 0.1 +/- 0.3 for the kinesio-tape group and 0.4 +/- 0.5 for the sham tape group (p > 0.05). DISCUSSION: Conservative treatment modalities are preferentially used for its treatment. Kinesiotherapy is one of the treatment methods for the apophysitis. In the literature, our study is the first prospective randomized trial on the efficacy of kinesio taping in calcaneal apophysitis. CONCLUSIONS: Although kinesio taping can be effectively used for the restoration of ankle functions of athletes with calcaneal apophysitis, its role in pain is limited. Since it lacks serious side effects, it can be used in combination with or as an alternative to pharmacological treatment in this patient group. PMID- 28985750 TI - Childhood diarrheal morbidity and sanitation predictors in a nomadic community. AB - BACKGROUND: Diarrhea remains a leading killer of young children on the globe despite the availability of simple and effective solutions to prevent and control it. The disease is more prevalent among under - five children (U5C) in the developing world due to lack of sanitation. A child dies every 15 s from diarrheal disease caused largely by poor sanitation. Nearly 90% of diarrheal disease is attributed to inadequate sanitation. Even though, the health burden of diarrheal disease is widely recognized at global level, its prevalence and sanitation predictors among a nomadic population of Ethiopia are not researched. This study was therefore designed to assess the prevalence of childhood diarrheal disease and sanitation predictors among a nomadic people in Hadaleala district, Afar region, Northeast Ethiopia. METHODS: A community based cross-sectional study design was carried out to investigate diarrheal disease among U5C. A total of 704 households who had U5C were included in this study and the study subjects were recruited by a multistage cluster sampling technique. Data were collected using a structured questionnaire and an observational checklist. All the mothers of U5C found in the selected clusters were interviewed. Furthermore, the living environment was observed. Univariable binary logistic regression analysis was used to choose variables for the multivariable binary logistic regression analysis on the basis of p- value less than 0.2. Finally, multivariable binary logistic regression analysis was used to identify variables associated with childhood diarrhea disease on the basis of adjusted odds ratio (AOR) with 95% confidence interval (CI) and p < 0.05. RESULTS: The two weeks period prevalence of diarrheal disease among U5C in Hadaleala district was 26.1% (95% CI: 22.9 - 29.3%). Childhood diarrheal disease was statistically associated with unprotected drinking water sources [AOR = 2.449, 95% CI = (1.264, 4.744)], inadequate drinking water service level [AOR = 1.535, 95% CI = (1.004, 2.346)], drinking water sources not protected from animal contact [AOR = 4.403, 95% CI = (2.424, 7.999)], un-availability of any type of latrine [AOR = 2.278, 95% CI = (1.045, 4.965)], presence of human excreta in the compound [AOR = 11.391, 95% CI = (2.100, 61.787)], not washing hand after visiting toilet [AOR = 16.511, 95% CI = (3.304, 82.509)], and live in one living room [AOR = 5.827, 95% CI = (3.208, 10.581)]. CONCLUSION: Childhood diarrheal disease was the common public health problem in Hadaleala district. Compared with the national and regional prevalence of childhood diarrhea, higher prevalence of diarrhea among U5C was reported. Types of drinking water sources, households whose water sources are shared with livestock, volume of daily water collected, availability of latrine, presence of faeces in the compound, hand washing after visiting the toilet and number of rooms were the sanitation predictors associated with childhood diarrhea. Therefore, enabling the community with safe and continuous supply of water and proper disposal of wastes including excreta is necessary with particular emphasis to the rural nomadic communities. PMID- 28985753 TI - Correction to: Breast cancer metastases to the thyroid gland - An uncommon sentinel for diffuse metastatic disease: A case report and literature review. PMID- 28985752 TI - Erratum to: MIIP remodels Rac1-mediated cytoskeleton structure in suppression of endometrial cancer metastasis. PMID- 28985754 TI - Cross protective immune responses in nursing piglets infected with a US spike insertion deletion porcine epidemic diarrhea virus strain and challenged with an original US PEDV strain. AB - We investigated cross-protective immunity of a US spike-insertion deletion porcine epidemic diarrhea virus (PEDV) Iowa106 (S-INDEL) strain against the original US PEDV (PC21A) strain in nursing piglets. Piglets were inoculated orally with S-INDEL, PC21A or mock. At 20-29 days post-inoculation (dpi), all pigs were challenged with the PC21A strain. The S-INDEL-inoculated pigs had lower ileal IgA antibody secreting cells, serum IgA and neutralizing antibody titers compared with PC21A-inoculated pigs. No pigs in the PC21A-group developed diarrhea, whereas 81 and 100% of pigs in the S-INDEL and mock-groups had diarrhea post challenge, respectively. S-INDEL induced partial protective immunity against the original US PEDV strain. PMID- 28985755 TI - A retrospective analysis of trends in maternal mortality in a Gambian tertiary health centre. AB - BACKGROUND: Maternal mortality ratio (MMR) has been on the decline in the Gambia since 1990. However, there has been no steady decline in maternal mortality ratio in the Edward Francis Small Teaching Hospital, the only tertiary health facility in the Gambia. The aim of the study is to determine the trend in maternal mortality over the last 8 years.A retrospective review of all maternal deaths occurring at the Edward Francis Small Teaching Hospital from 1st January 2007 to 31st December 2014 was done. Case abstraction was done with a pre-structured questionnaire using the WHO definition of maternal mortality. RESULTS: There were 663 maternal deaths recorded during the study period. During the same period the total number of live births were 38,896. The annual MMR in each year varied with a range between 1461 and 2105 per 100,000 live births. The MMR in the hospital in on the rise compared to earlier studies. The causes of maternal mortality have not changed much in the hospital. However, the seasonal variation in maternal mortality in earlier studies attributed to the influence of malaria and anaemia was not seen in this study. We attribute this change to the widespread use of intermittent prophylactic treatment for malaria in the antenatal period. CONCLUSION: While MMR was decreasing in the country, it was increasing in the only tertiary health facility in the country. This was attributed to increasing referrals from other health facilities. The influence of malaria and anemia as a cause of maternal mortality seems to be declining. PMID- 28985757 TI - Bayesian nonparametric estimation of EQ-5D utilities for United States using the existing United Kingdom data. AB - BACKGROUND: Valuations of health state descriptors such as EQ-5D or SF6D have been conducted in different countries. There is a scope to make use of the results in one country as informative priors to help with the analysis of a study in another, for this to enable better estimation to be obtained in the new country than analyzing its data separately. METHODS: Data from 2 EQ-5D valuation studies were analyzed using the time trade-off technique, where values for 42 health states were devised from representative samples of the UK and US populations. A Bayesian non-parametric approach has been applied to predict the health utilities of the US population, where the UK results were used as informative priors in the model to improve their estimation. RESULTS: The findings showed that employing additional information from the UK data helped in the production of US utility estimates much more precisely than would have been possible using the US study data alone. CONCLUSION: It is very plausible that this method would serve useful in countries where the conduction of large evaluation studies is not very feasible. PMID- 28985756 TI - Extracranial metastases of high-grade glioma: the clinical characteristics and mechanism. AB - BACKGROUND: This presentation of two cases and literature review discusses the epidemiology, clinical manifestations, pathogenesis, diagnosis, treatment, and prognosis of high-grade glioma with extracranial metastases. METHODS: A retrospective analysis of the clinical features of two cases of malignant glioma, including metastatic sites, pathological data, and treatment methods, and a literature review was performed. RESULTS: Two patients developed extracranial metastases within 1 year after surgery for primary glioma. One patient developed cervical lymph node and bone metastases while the other developed bone metastases, and both patients died within 2 months after the diagnosis of the extracranial metastasis. CONCLUSION: Extracranial metastases may develop from malignant gliomas. According to the literature, the most common extracranial site is intraspinal (along the neural axis), followed by the vertebrae, lungs, liver, and lymph nodes. The complex metastatic mechanism remains unclear, and the prognosis is very poor, with a survival duration of less than 6 months. PMID- 28985758 TI - Pharmacological targeting of the ephrin receptor kinase signalling by GLPG1790 in vitro and in vivo reverts oncophenotype, induces myogenic differentiation and radiosensitizes embryonal rhabdomyosarcoma cells. AB - BACKGROUND: EPH (erythropoietin-producing hepatocellular) receptors are clinically relevant targets in several malignancies. This report describes the effects of GLPG1790, a new potent pan-EPH inhibitor, in human embryonal rhabdomyosarcoma (ERMS) cell lines. METHODS: EPH-A2 and Ephrin-A1 mRNA expression was quantified by real-time PCR in 14 ERMS tumour samples and in normal skeletal muscle (NSM). GLPG1790 effects were tested in RD and TE671 cell lines, two in vitro models of ERMS, by performing flow cytometry analysis, Western blotting and immunofluorescence experiments. RNA interfering experiments were performed to assess the role of specific EPH receptors. Radiations were delivered using an x-6 MV photon linear accelerator. GLPG1790 (30 mg/kg) in vivo activity alone or in combination with irradiation (2 Gy) was determined in murine xenografts. RESULTS: Our study showed, for the first time, a significant upregulation of EPH-A2 receptor and Ephrin-A1 ligand in ERMS primary biopsies in comparison to NSM. GLPG1790 in vitro induced G1-growth arrest as demonstrated by Rb, Cyclin A and Cyclin B1 decrease, as well as by p21 and p27 increment. GLPG1790 reduced migratory capacity and clonogenic potential of ERMS cells, prevented rhabdosphere formation and downregulated CD133, CXCR4 and Nanog stem cell markers. Drug treatment committed ERMS cells towards skeletal muscle differentiation by inducing a myogenic-like phenotype and increasing MYOD1, Myogenin and MyHC levels. Furthermore, GLPG1790 significantly radiosensitized ERMS cells by impairing the DNA double-strand break repair pathway. Silencing of both EPH-A2 and EPH-B2, two receptors preferentially targeted by GLPG1790, closely matched the effects of the EPH pharmacological inhibition. GLPG1790 and radiation combined treatments reduced tumour mass by 83% in mouse TE671 xenografts. CONCLUSIONS: Taken together, our data suggest that altered EPH signalling plays a key role in ERMS development and that its pharmacological inhibition might represent a potential therapeutic strategy to impair stemness and to rescue myogenic program in ERMS cells. PMID- 28985760 TI - An improved pre-clinical patient-derived liquid xenograft mouse model for acute myeloid leukemia. AB - BACKGROUND: Xenotransplantation of patient-derived AML (acute myeloid leukemia) cells in NOD-scid Il2rgamma null (NSG) mice is the method of choice for evaluating this human hematologic malignancy. However, existing models constructed using intravenous injection in adult or newborn NSG mice have inferior engraftment efficiency, poor peripheral blood engraftment, or are difficult to construct. METHODS: Here, we describe an improved AML xenograft model where primary human AML cells were injected into NSG newborn pups intrahepatically. RESULTS: Introduction of primary cells from AML patients resulted in high levels of engraftment in peripheral blood, spleen, and bone marrow (BM) of recipient mice. The phenotype of engrafted AML cells remained unaltered during serial transplantation. The mice developed features that are consistent with human AML including spleen enlargement and infiltration of AML cells into multiple organs. Importantly, we demonstrated that although leukemic stem cell activity is enriched and mediated by CD34+CD117+ subpopulation, CD34+CD117- subpopulation can acquire CD34+CD117+ phenotype through de differentiation. Lastly, we evaluated the therapeutic potential of Sorafenib and Regorafenib in this AML model and found that periphery and spleen AML cells are sensitive to these treatments, whereas BM provides a protective environment to AML. CONCLUSIONS: Collectively, our improved model is robust, easy-to-construct, and reliable for pre-clinical AML studies. PMID- 28985759 TI - Role of microglial amylin receptors in mediating beta amyloid (Abeta)-induced inflammation. AB - BACKGROUND: Neuroinflammation in the brain consequent to activation of microglia is viewed as an important component of Alzheimer's disease (AD) pathology. Amyloid beta (Abeta) protein is known to activate microglia and unleash an inflammatory cascade that eventually results in neuronal dysfunction and death. In this study, we sought to identify the presence of amylin receptors on human fetal and murine microglia and determine whether Abeta activation of the inflammasome complex and subsequent release of cytokines is mediated through these receptors. METHODS: The presence of dimeric components of the amylin receptor (calcitonin receptor and receptor activity modifying protein 3) were first immunohistochemically identified on microglia. Purified human fetal microglial (HFM) cultures were incubated with an in vivo microglial marker, DyLight 594-conjugated tomato lectin, and loaded with the membrane-permeant green fluorescent dye, Fluo-8L-AM for measurements of intracellular calcium [Ca2+]i. HFM and BV-2 cells were primed with lipopolysaccharide and then exposed to either human amylin or soluble oligomeric Abeta1-42 prior to treatment with and without the amylin receptor antagonist, AC253. Changes in the inflammasome complex, NLRP3 and caspase-1, were examined in treated cell cultures with Western blot and fluorometric assays. RT-PCR measurements were performed to assess cytokine release. Finally, in vivo studies were performed in transgenic mouse model of AD (5xFAD) to examine the effects of systemic administration of AC253 on markers of neuroinflammation in the brain. RESULTS: Acute applications of human amylin or Abeta1-42 resulted in an increase in [Ca2+]i that could be blocked by the amylin receptor antagonist, AC253. Activation of the NLRP3 and caspase-1 and subsequent release of cytokines, TNFalpha and IL-1beta, was diminished by AC253 pretreatment of HFMs and BV2 cells. In vivo, intraperitoneal administration of AC253 resulted in a reduction in microglial markers (Iba-1 and CD68), caspase-1, TNFalpha, and IL-1beta. These reductions in inflammatory markers were accompanied by reduction in amyloid plaque and size in the brains of 5xFAD mice compared to controls. CONCLUSION: Microglial amylin receptors mediate Abeta-evoked inflammation, and amylin receptor antagonists therefore offer an attractive therapeutic target for intervention in AD. PMID- 28985761 TI - Socioeconomic and urban-rural differentials in exposure to air pollution and mortality burden in England. AB - BACKGROUND: Socioeconomically disadvantaged populations often have higher exposures to particulate air pollution, which can be expected to contribute to differentials in life expectancy. We examined socioeconomic differentials in exposure and air pollution-related mortality relating to larger scale (5 km resolution) variations in background concentrations of selected pollutants across England. METHODS: Ozone and particulate matter (sub-divided into PM10, PM2.5, PM2.5-10, primary, nitrate and sulphate PM2.5) were simulated at 5 km horizontal resolution using an atmospheric chemistry transport model (EMEP4UK). Annual mean concentrations of these pollutants were assigned to all 1,202,578 residential postcodes in England, which were classified by urban-rural status and socioeconomic deprivation based on the income and employment domains of the 2010 English Index of Multiple Deprivation for the Lower-level Super Output Area of residence. We used life table methods to estimate PM2.5-attributable life years (LYs) lost in both relative and absolute terms. RESULTS: Concentrations of the most particulate fractions, but not of nitrate PM2.5 or ozone, were modestly higher in areas of greater socioeconomic deprivation. Relationships between pollution level and socioeconomic deprivation were non-linear and varied by urban rural status. The pattern of PM2.5 concentrations made only a small contribution to the steep socioeconomic gradient in LYs lost due to PM2.5 per 103 population, which primarily was driven by the steep socioeconomic gradient in underlying mortality rates. In rural areas, the absolute burden of air pollution-related LYs lost was lowest in the most deprived deciles. CONCLUSIONS: Air pollution shows modest socioeconomic patterning at 5 km resolution in England, but absolute attributable mortality burdens are strongly related to area-level deprivation because of underlying mortality rates. Measures that cause a general reduction in background concentrations of air pollution may modestly help narrow socioeconomic differences in health. PMID- 28985762 TI - A study of Epstein-Barr virus infection in the Chinese tree shrew(Tupaia belangeri chinensis). AB - BACKGROUND: Epstein-Barr virus (EBV) is closely associated with many human diseases, including a variety of deadly human malignant tumours. However, due to the lack of ideal animal models,the biological characteristics of EBV, particularly its function in tumourigenesis, have not been determined. Chinese tree shrews (Tupaia belangeri chinensis), which are similar to primates, have been used to establish a variety of animal models and have recently received much attention. Here, we established tree shrews as a model for EBV infection by intravenous injection. METHODS: Ten tree shrews were inoculated with EBV by intravenous injection,and blood was collected at regular intervals thereafter from the femoral artery or vein to detect EBV markers. RESULTS: Eight of 10 tree shrews showed evidence of EBV infection. In the 8 EBV-infected tree shrews, EBV copy number increased intermittently or transiently, EBV-related gene expression was detected, and anti-EBV antibodies increased to varying degrees. Macroscopic hepatomegaly was observed in 1 tree shrew, splenomegaly was observed in 4 tree shrews, and enlarged mesenteric lymph nodes were observed in 3 tree shrews. Haematoxylin and eosin (HE) staining showed splenic corpuscle hyperplasia in the spleens of 4 tree shrews and inflammatory cell infiltration of the liver of 1 tree shrew and of the mesenteric lymph nodes of 3 tree shrews. EBER in situ hybridization(ISH) and immunohistochemical (IHC) staining showed that EBER-, LMP1 and EBNA2- positive cells were present in the spleens and mesenteric lymph nodes of some tree shrews. Western blotting (WB) revealed EBNA1-positive cells in the spleens of 4 tree shrews. EBV markers were not detected by HE, EBER-ISH or IHC in the lung or nasopharynx. CONCLUSIONS: These findings suggest that EBV can infect tree shrews via intravenous injection. The presented model offers some advantages for exploring the pathophysiology of EBV infection in humans. PMID- 28985763 TI - Crossing enhanced and high fidelity SpCas9 nucleases to optimize specificity and cleavage. AB - BACKGROUND: The propensity for off-target activity of Streptococcus pyogenes Cas9 (SpCas9) has been considerably decreased by rationally engineered variants with increased fidelity (eSpCas9; SpCas9-HF1). However, a subset of targets still generate considerable off-target effects. To deal specifically with these targets, we generated new "Highly enhanced Fidelity" nuclease variants (HeFSpCas9s) containing mutations from both eSpCas9 and SpCas9-HF1 and examined these improved nuclease variants side by side to decipher the factors that affect their specificities and to determine the optimal nuclease for applications sensitive to off-target effects. RESULTS: These three increased-fidelity nucleases can routinely be used only with perfectly matching 20-nucleotide-long spacers, a matching 5' G extension being more detrimental to their activities than a mismatching one. HeFSpCas9 exhibit substantially improved specificity for those targets for which eSpCas9 and SpCas9-HF1 have higher off-target propensity. The targets can also be ranked by their cleavability and off-target effects manifested by the increased fidelity nucleases. Furthermore, we show that the mutations in these variants may diminish the cleavage, but not the DNA-binding, of SpCas9s. CONCLUSIONS: No single nuclease variant shows generally superior fidelity; instead, for highest specificity cleavage, each target needs to be matched with an appropriate high-fidelity nuclease. We provide here a framework for generating new nuclease variants for targets that currently have no matching optimal nuclease, and offer a simple means for identifying the optimal nuclease for targets in the absence of accurate target-ranking prediction tools. PMID- 28985765 TI - Identifying effective components for mobile health behaviour change interventions for smoking cessation and service uptake: protocol of a systematic review and planned meta-analysis. AB - BACKGROUND: Mobile health (mHealth) interventions for smoking cessation have been shown to be associated with an increase in effectiveness. However, interventions using mobile phones to change people's behaviour are often perceived as complex interventions, and the interactions between several components within them may affect the outcome. Therefore, it is important to understand how we can improve the design of mHealth interventions using mobile phones as a medium to deliver services. METHODS: Randomised controlled trials (RCTs) of mHealth interventions to support smoking cessation or uptake of smoking cessation services for smokers will be included in this systematic review. A search will be performed by searching MEDLINE, MEDLINE(R) In-Process & Other Non-Indexed Citations, EMBASE, PsycINFO, Web of Science, and CINAHL. A search for new publications will be conducted 3 months prior to submission for publication as mHealth is an emerging area of research. A random-effects meta-analysis model will be used to summarise the effectiveness of mHealth interventions. The risk ratio will be used for the primary outcome, self-reported or verified smoking abstinence, and any binary outcomes for uptake of smoking cessation services. The standardised mean difference using Hedges' g will be reported for continuous data. Heterogeneity will be assessed using I 2 statistics. Where feasible, meta-regression analysis using random-effects multilevel modelling will be conducted to examine the association of pre-specified characteristics (covariates) at the study level with the effectiveness of interventions. Publication bias will be explored using Egger's test for continuous outcomes and Harbord and Peters tests for dichotomous outcomes. The funnel plot will be used to evaluate the presence of publication bias. The Cochrane Risk of Bias Tool will be used to assess differences in risks of bias. DISCUSSION: The results of this systematic review will provide future research with a foundation for designing and evaluating complex interventions that use mobile phones as a platform to deliver behaviour change techniques. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016026918 . PMID- 28985764 TI - Identification of differential genomic DNA Methylation in the hypothalamus of pubertal rat using reduced representation Bisulfite sequencing. AB - BACKGROUND: There are many variables affecting the onset of puberty in animals, including genetic, nutritional, and environmental factors. Recent studies suggest that epigenetic regulation, especially DNA methylation, plays a majorrole in the regulation of puberty. However, there have been no reports on DNA methylation of the pubertal genome. METHODS: We investigated DNA methylation in the female rat hypothalamus at prepuberty and puberty using reduced representation bisulfite sequencing technology. The identified genes and signaling pathways exhibiting changes to DNA methylation in pubertal rats were determined by Gene Ontogeny and Kyoto Encyclopedia of Genes and Genomes analysis. RESULTS: The distribution of the three types of methylated C bases in promoter and CpG island (CGI) regions in the hypothalamus was as follows: 87.79% CG, 3.05% CHG, 9.16% CHH for promoters, and 88.35% CG, 3.21% CHG, 88.35% CHH for CGI in prepubertal rats; and 90.78% CG, 2.13% CHG, 7.09% CHH for promoters, and 88.59% CG, 88.59% CHG, 8.35% CHH for CGI in pubertal animals. CG showed the highest percentage of methylation, and was the highest methylation state in CGI. Compared to prepubertal hyoyhalamus samples, we identified ten genes with altered methylation in promoter regions in the pubertal hypothalamus samples, and 43 genes with altered methylation in the CGI. Changes in DNA methylation were found in gonadotropin-releasing hormone signaling pathways, and the oocyte meiosis pathway. CONCLUSION: Our results demonstrate changes in DNA methylation occur in female rats from prepuberty to puberty suggestng DNA methylation may play a crucial role in the regulation of puberty onset. This study provides essential information for future studies on the role of epigenetics in the regulation of puberty. PMID- 28985766 TI - Mutations in BRCA1, BRCA2 and other breast and ovarian cancer susceptibility genes in Central and South American populations. AB - Breast cancer (BC) is the most common malignancy among women worldwide. A major advance in the understanding of the genetic etiology of BC was the discovery of BRCA1 and BRCA2 (BRCA1/2) genes, which are considered high-penetrance BC genes. In non-carriers of BRCA1/2 mutations, disease susceptibility may be explained of a small number of mutations in BRCA1/2 and a much higher proportion of mutations in ethnicity-specific moderate- and/or low-penetrance genes. In Central and South American populations, studied have focused on analyzing the distribution and prevalence of BRCA1/2 mutations and other susceptibility genes that are scarce in Latin America as compared to North America, Europe, Australia, and Israel. Thus, the aim of this review is to present the current state of knowledge regarding pathogenic BRCA variants and other BC susceptibility genes. We conducted a comprehensive review of 47 studies from 12 countries in Central and South America published between 2002 and 2017 reporting the prevalence and/or spectrum of mutations and pathogenic variants in BRCA1/2 and other BC susceptibility genes. The studies on BRCA1/2 mutations screened a total of 5956 individuals, and studies on susceptibility genes analyzed a combined sample size of 11,578 individuals. To date, a total of 190 different BRCA1/2 pathogenic mutations in Central and South American populations have been reported in the literature. Pathogenic mutations or variants that increase BC risk have been reported in the following genes or genomic regions: ATM, BARD1, CHECK2, FGFR2, GSTM1, MAP3K1, MTHFR, PALB2, RAD51, TOX3, TP53, XRCC1, and 2q35. PMID- 28985767 TI - Acute suppurative appendicitis associated with Enterobius vermicularis: an incidental finding or a causative agent? A case report. AB - BACKGROUND: Histological acute appendicitis patterns associated with Enterobius vermicularis is an extremely rare finding. The exact role of this parasite in acute appendicitis is controversial as usually resected specimens show no evidence of histological inflammation. CASE PRESENTATION: We present herein a case of a 21-year-old male Arabic patient who presented with clinical syndrome of acute appendicitis. Emergency appendectomy was performed and the histopathological examination of the resected specimen showed the presence of E. vermicularis as well as intense acute inflammatory patterns such as mucosal ulceration and suppurative necrosis. The post-operative course was uneventful and the patient was discharged with appropriate anti-helmintic drug prescription. CONCLUSION: Acute appendicitis due to E. vermicularis is a very rare occurrence. The histopathological analysis of resected specimens should pay special attention to search for this parasite for adequate post-operative treatment of patients. PMID- 28985769 TI - Low toxicity and favorable clinical and quality of life impact after non myeloablative autologous hematopoietic stem cell transplant in Crohn's disease. AB - OBJECTIVE: The incidence of adverse events in myeloablative transplant protocols is high in refractory Crohn's disease; this study used low doses of cyclophosphamide. Fourteen patients were submitted to non-myeloablative autologous hematopoietic stem cell transplantation. RESULTS: The average number of days of anemia (hemoglobin < 10 g/dL) was 5.4 +/- 4.2 and 14 +/- 2.4 in the mobilization and conditioning phases, respectively. The mean number of days of neutropenia (neutrophils < 0.5 * 109/L) in the mobilization phase was 1.7 +/- 1.5 while it was 7.6 +/- 1.4 in the conditioning phase. When comparing the conditioning and mobilization phases, there was an increased number days of leukopenia (white blood cells < 1.0 * 109/L), lymphocytopenia (lymphocytes < 0.5 * 109/L) and thrombocytopenia (platelets < 25 * 109/L). Crohn's Disease Activity Index values before the transplant ranged from 155 to 450.5 (mean 281.2 +/- 79.0) and at 30 days after the procedures they ranged from 45.4 to 177 (mean 95.8 +/- 35.4). Moreover, the procedure improved in overall quality of life of patients. Non-myeloablative autologous hematopoietic stem cell transplantation with lower doses of cyclophosphamide leads to lower rates of hematological toxicity and adverse events compared to protocols described in the literature. Trial registration NCT 03000296: Date 9 December 2016. PMID- 28985768 TI - Immune thrombocytopenia with multi-organ dysfunction syndrome as a rare presentation of scrub typhus: a case report. AB - BACKGROUND: Scrub typhus is an acute infectious illness caused by Orientia tsutsugamushi. It is endemic to a part of the world known as the "tsutsugamushi triangle". Humans are accidental hosts in this zoonotic disease. About a third of patients admitted with scrub typhus have evidence of multi-organ dysfunction. Multi-organ dysfunction secondary to scrub typhus carries a high mortality rate. CASE PRESENTATION: We report a 65-year old lady who was admitted in a Tertiary Care Center in the state of Kerala in India, with 7 day history of fever, myalgia and reduced urine output. Head to foot examination revealed the presence of an eschar on her chest. One week prior to the onset of her illness she had gone trekking through a hilly forest area. She was clinically suspected to have scrub typhus, which was later confirmed with laboratory tests. She developed multi organ dysfunction syndrome secondary to this illness. Though there was an improvement in the multi-organ dysfunction, thrombocytopenia alone failed to improve. Bone marrow study was done which was suggestive of immune thrombocytopenia. Patient was given a course of steroids with which the thrombocytopenia improved. CONCLUSION: Failure of platelet count to normalize even after there has been a general improvement of other markers of multi-organ dysfunction in scrub typhus should prompt the clinician to consider other potential causes of thrombocytopenia. An unusual finding as this calls for further research to understand the molecular mechanisms behind such an event. Further, considering the close similarity in clinical presentation of several tropical illnesses, meticulous history taking and a detailed physical examination needs to be emphasized. PMID- 28985770 TI - Systemic inflammation mediates the detrimental effects of obesity on asthma control. AB - BACKGROUND: Obesity negatively impacts asthma control, but the inflammatory mechanisms are poorly understood. OBJECTIVE: To explore which systemic inflammatory mediators mediate the effects of obesity on asthma control. METHODS: The subjects with stable asthma (n = 108) underwent assessment of clinical characteristics, which included usingThe Asthma Control Questionnaire (ACQ)-6. Obesity was defined as a body mass index (BMI) of more than or equal to 30 kg/m2, overweight was defined as BMI between 25 to 29.9 kg/m2, and lean weight was defined as BMI < 25 kg/m2. Body composition, including fat mass (FM), visceral fat area (VFA), and percentage body fat (PBF) was analyzed by bioimpedance. Serum interleukin (IL) 4, IL-5, IL-8, IL-13, IL-17, chemokine (C-C motif) ligand (CCL) 17, CCL22, leptin, adiponectin, C-reactive protein (CRP), and interferon (IFN) gamma were measured by using ELISA. Linear regression models were fitted according to the Baron and Kenny procedures for mediation analysis. RESULTS: FM (12.73 +/- 3.95 versus 18.59 +/- 2.95 versus 27.82 +/- 5.17 kg; p < 0.0001), VFA (65.99 +/- 23.17 versus 93.96 +/- 10.28 versus 123.10 +/- 18.34 cm2; p < 0.0001), PBF (23.86 +/- 7.46 versus 30.74 +/- 5.08 versus 36.21 +/- 6.28 %; p = 0.0003)and ACQ-6 values (0.83 [0, 1.17]) versus 1.15 [0.50, 1.75] versus 1.33 [0.83, 1.83] score; p = 0.002) were different amonglean (n = 52), overweight (n = 37), and obese (n = 19) subjects. Serum levels of leptin, IL-5, IL-13, IL-17, CCL17, CRP, andIFN-gamma in the obese group were significantly elevated compared with the subjects who were lean or overweight (all p < 0.05). The mediation analyses found that the effect of obesity, assessed by BMI, on ACQ-6 was significantly mediated throughIL-13 and CCL17. Furthermore, IL-13 and CCL17 mediated the effects of body composition (FM, VFA and PBF) on ACQ-6. The effects of obesity assessed by body composition, but not by using BMI, on ACQ-6 were mediated by leptin. CONCLUSION: Our mediation analysis confirmed that systemic inflammation biomarkers, such as leptin, CCL17, IL-4, andIL-13, mediated the effects of obesity on asthma control. This warrants prospective exploration in this distinct asthma phenotype in the future. PMID- 28985771 TI - Novel Two-Stage Fine Milling Enables High-Throughput Determination of Glyphosate Residues in Raw Agricultural Commodities. AB - Dramatic process-efficiency gains for residue analysis of glyphosate in raw agricultural commodities (RACs) were achieved by development and validation of a two-stage fine-milling process. This secondary milling produced a uniform and consistent product that could be reproducibly measured with 75 mg analytical test portions. The milligram scale sample size enabled the direct weighing of sample into a liquid-handler-compatible 96-well format. A high-throughput workflow based on this innovative comminution approach for the quantitation of glyphosate, a nonselective herbicide, and its main degradation product, aminomethylphosphonic acid, was validated in various RACs and used to demonstrate the applicability of the two-step milling process. The precision and reproducibility of 75 mg analytical portions taken through this assay was used to demonstrate the feasibility of using a two-stage fine-milling technique for pesticide residue applications. An RSD of less than 10% was achieved in endogenous glyphosate residues in multiple RACs. Comparable recoveries and superior precision were achieved with this new method as compared with a validated 10 g scale method. PMID- 28985772 TI - ? PMID- 28985773 TI - ? PMID- 28985774 TI - [ERAS, from concept to care]. AB - Enhanced recovery after surgery (ERAS) aims at reducing the length of hospital stays and complications. Everyone has a role to play - healthcare professionals, medical secretaries, administrative staff and patients. A coordinated treatment pathway must be ensured and changes in practices must be accepted. PMID- 28985775 TI - [Making patients actors in their own care]. AB - Enhanced recovery after surgery is a caregiving method focusing on the patient. It aims at ensuring faster recovery of the patient's functional abilities after surgery for a rapid return to the everyday environment and activities with total safety. PMID- 28985776 TI - [Toward innovative hospital care]. AB - For healthcare financing to remain profitable and to continue to function, the care system must be innovative in terms of patient care. Work organisation has changed with the pricing system for medical acts. The system of enhanced recovery after surgery helps to reduce hospitalisation times and to reflect on organisation. Nurses are on the front line. PMID- 28985777 TI - [Follow-up care at home after outpatient surgery]. AB - Private nurses have an important role to play in the healthcare system, notably within the framework of outpatient surgery. They are often underestimated, but they are on the front lines when it comes to informing patients, reassuring them and caring for them. They must therefore master the processes of outpatient surgery and those of enhanced recovery after surgery. Their skills need to be upgraded. PMID- 28985778 TI - [Implementing an ERAS protocol]. AB - An orthopaedic surgeon at Clinique Saint-Augustin in Nantes has joined the label developed by the Groupe Francophone de Rehabilitation Amelioree apres Chirurgie (Francophone Group for Enhanced Recovery After Surgery. The establishment has taken an interest in this approach and is promoting it by applying the recommendations issued by the Haute Autorite de Sante (French National Health Authority) for this new circuit. PMID- 28985779 TI - ? PMID- 28985781 TI - [Happy feet, happy caregivers]. AB - Healthcare professionals take care of their patients' feet. But how much attention do they pay to their own feet, which they use all day long? Perspectives on prevention and the connection between healthy feet and wellbeing. PMID- 28985780 TI - [Schizophrenia, automobile driving and virtual simulation]. AB - A psychiatric nurse working at a day hospital discusses an innovative approach to care for patients suffering from schizophrenia. This approach focuses on the patients' everyday life through a project for obtaining a driving licence using innovative technologies. PMID- 28985782 TI - [Electrocardiograms: derived derivations!] AB - Simple and non-invasive, the electrocardiogram is a basic examination for studying how the cardiac muscle functions. Very commonly used, it nonetheless requires great rigour when applying the electrodes to avoid false results that can be harmful to appropriate care for the patient. A reminder of good practices. PMID- 28985784 TI - ? PMID- 28985783 TI - [Fencing for promoting health after breast cancer]. AB - Physical activity is recommended after breast cancer surgery. Fencing is a sport that is well suited to combatting fatigue, pain and reduced arm mobility. A healthcare executive, herself a fencer, puts the benefits of this sport into perspective, both physically and psychologically. PMID- 28985785 TI - ? PMID- 28985786 TI - ? PMID- 28985787 TI - ? PMID- 28985788 TI - ? PMID- 28985789 TI - [Anales de pediatria: Achieving milestones]. PMID- 28985790 TI - [Anales De Pediatria: Onward and upward]. PMID- 28985791 TI - New International Guidelines for the Interpretation of the Electrocardiograph in Athletes: a "Traffic Light" Tool for Maximising Diagnostic Specificity. PMID- 28985792 TI - Renal Failure and Right Heart Failure After Left Ventricular Assist Device Implantation: Which Is Cause and Which Is Effect? PMID- 28985793 TI - Intraocular Phenylephrine-Induced Takotsubo Syndrome. PMID- 28985794 TI - Cardiac Syndrome X, Vitamin D, and Lipoprotein(a). PMID- 28985795 TI - Comparison of Risk 'Scores' Performances for Combined Aortic Valve Replacement and Coronary Artery Bypass Surgery. PMID- 28985796 TI - Assessing Contemporary Risk Models' Performance in Cardiac Surgery. PMID- 28985799 TI - Teaching binocular indirect ophthalmoscopy to novice residents using an augmented reality simulator. AB - OBJECTIVE: To compare the traditional teaching approach of binocular indirect ophthalmoscopy (BIO) to the EyeSI augmented reality (AR) BIO simulator. DESIGN: Prospective randomized control trial. PARTICIPANTS: 28 post-graduate year one (PGY1) ophthalmology residents. METHODS: Residents were recruited at the 2012 Toronto Ophthalmology Residents Introductory Course (TORIC). 15 were randomized to conventional teaching (Group 1), and 13 to augmented reality simulator training (Group 2). 3 vitreoretinal fellows were enrolled to serve as experts. Evaluations were completed on the simulator, with 3 tasks, and outcome measures were total raw score, total time elapsed, and performance. RESULTS: Following conventional training, Group 1 residents were outperformed by vitreoretinal fellows with respect to all 3 outcome measures. Following AR training, Group 2 residents demonstrated superior total scores and performance compared to Group 1 residents. Once the Group 1 residents also completed the AR BIO training, there was a significant improvement compared to their baseline scores, and were now on par with Group 2 residents. CONCLUSIONS: This study provides construct validity for the EyeSI AR BIO simulator and demonstrates that it may be superior to conventional BIO teaching for novice ophthalmology residents. PMID- 28985800 TI - The application of a "6S Lean" initiative to improve workflow for emergency eye examination rooms. AB - BACKGROUND: Ophthalmology residents on call at the Royal Alexandra Hospital identified workplace disorganization and lack of standardization in emergency eye examination rooms as an impediment to efficient patient treatment. OBJECTIVE: The aim of the study was to use the "6S Lean" model to improve workflow in eye examination rooms at the Royal Alexandra Hospital. METHODS: With the assistance of quality improvement consultants, the "6S Lean" model was applied to the current operation of the emergency eye clinic examination rooms. This model, considering 8 waste categories, was then used to recommend and implement changes to the examination rooms and to workplace protocols to enhance efficiency and safety. RESULTS: Eye examination rooms were improved with regards to setup, organization of supplies, inventory control, and maintenance. All targets were achieved, and the 5S audit checklist score increased by 33 points from 44 to 77. CONCLUSIONS: Implementation of the 6S methodology is a simple approach that removes inefficiencies from the workplace. The ophthalmology clinic removed waste from all 8 waste categories, increased audit results, mitigated patient and resident safety risks, and ultimately redirected resident time back to patient care delivery. PMID- 28985801 TI - Evaluation of an online peer fundus photograph matching program in teaching direct ophthalmoscopy to medical students. AB - OBJECTIVE: Direct ophthalmoscopy is an important clinical skill that is often poorly performed by medical professionals and students. This is attributable to a declining emphasis on ophthalmology in medical school. We present and evaluate a self-directed approach of teaching ophthalmoscopy to medical students that is suitable for the current medical curriculum. DESIGN: Prospective medical education trial. PARTICIPANTS: Ninety-five second-year medical students at Queen's University: 32 in the experimental group and 63 in the control group. METHODS: The experimental group consisted of medical students who practised ophthalmoscopy with one another using an online peer fundus photograph matching exercise created by the Department of Ophthalmology at Queen's University. To use the program, students first examined a peer with an ophthalmoscope and then selected an online photograph of a fundus corresponding to that of the examinee. The program notifies students if a correct selection is made. To encourage use of the program, students participated in a 2-week ophthalmoscopy competition during their ophthalmology rotation. The control group consisted of students who did not participate in the learning exercise. RESULTS: On assessment at the end of the ophthalmology rotation, the experimental group (n = 32) was more accurate in matching fundus photographs compared with the control group (n = 63) (p = 0.02). Participants were faster at performing ophthalmoscopy at the end of the learning exercise (p < 0.01). All students in the experimental group reported increased confidence levels in ophthalmoscopy after participation in the learning exercise. CONCLUSIONS: Matching online peer fundus photographs in a self-directed manner appeared to increase the skill and confidence of medical students in ophthalmoscopy. PMID- 28985802 TI - Creation and validation of a simulator for corneal rust ring removal. AB - OBJECTIVE: To create and validate a simulation model for corneal rust ring removal. METHODS: Rust rings were created on cadaveric eyes with the use of small particles of metal. The eyes were mounted on suction plates at slit lamps and the trainees practiced rust ring removal. An inexperienced cohort of medical students and first year ophthalmology residents (n=11), and an experienced cohort of senior residents and faculty (n=11) removed the rust rings from the eyes with the use of a burr. Rust ring removal was evaluated based on removal time, percentage of rust removed and incidence of corneal perforation. A survey was administered to participants to determine face validity. RESULTS: Time for rust ring removal was longer in the inexperienced group at 187+/-93 seconds (range of 66-408 seconds), compared to the experienced group at 117+/-54 seconds (range of 55-240 seconds) (p=0.046). Removal speed was similar between groups, at 4847+/-4355 pixels/minute and 7206+/-5181 pixels/minute in the inexperienced and experienced groups, respectively (p=0.26). Removal percentage values were similar between groups, at 61+/-15% and 69+/-18% (p=0.38). There were no corneal perforations. 100% (22/22) of survey respondents believed the simulator would be a valuable practice tool, and 89% (17/19) felt the simulation was a valid representation of the clinical correlate. CONCLUSION: The corneal rust ring simulator presented here is a valid training tool that could be used by early trainees to gain greater comfort level before attempting rust ring removal on a live patient. PMID- 28985804 TI - Adult patients with uveitis associated with juvenile idiopathic arthritis: a retrospective review. AB - OBJECTIVE: To describe clinical characteristics and outcomes of adults with uveitis associated with juvenile idiopathic arthritis (JIA). METHODS: Retrospective chart review from 2001 to 2014 of adult patients with JIA and follow-up >=2 months. Outcome measures included visual acuity, intraocular pressure (IOP), inflammation grade, ocular findings/complications, immunosuppressive therapies, and surgeries. RESULTS: Nineteen patients were included (95% female, 84% bilateral uveitis, 47% anterior uveitis). Mean (SD) ages at presentation and JIA diagnosis were 25.6 (7.8) years and 8.9 (5.6) years, respectively. Visual acuity and IOP did not significantly change throughout the study. Mean (SD) presenting inflammation grade was significantly decreased at 6 and 12 months. Fifteen (79%) patients were on topical medications, and 17 (89%) were on systemic immunosuppression. Two (12%) patients developed side effects requiring medication cessation. CONCLUSION: Uveitis associated with JIA may extend into adulthood despite the use of topical medications and/or systemic immunosuppression and result in significant ocular morbidity, including the need for surgical intervention. PMID- 28985803 TI - Flashes and floaters: a survey of Canadian ophthalmology residents' practice patterns. AB - BACKGROUND: Residents are often the first point of contact in assessing patients who present with "flashes and floaters" in the emergency ophthalmology clinic. Most often, these symptoms are attributed to a posterior vitreous detachment (PVD), which may be associated with a retinal tear in up to 14% of cases. A proper peripheral retinal exam is, thus, imperative, and techniques other than scleral depression may not be sufficient. We conducted a cross-sectional survey of Canadian ophthalmology residents-in-training to understand the current resident practice patterns for examination of the peripheral retina. METHODS: Anonymous electronic survey of all Canadian ophthalmology residents (postgraduate years 2-5). RESULTS: On average, residents (n = 47) perform a peripheral retinal examination 5 to 7 times per day in the emergency clinic and on call. Reported techniques for assessing the peripheral retina include scleral depression with indirect ophthalmoscopy alone (45.7%), scleral depression combined with the 3 mirror (15.2%) or panretinal lens (10.9%), or each of these techniques alone (23.9% and 4.3%, respectively). The major factors deterring resident use of scleral depression include history of recent trauma (47.5%), patient discomfort (16.3%), personal discomfort (16.3%), or lack of time (13.8%). CONCLUSIONS: Although scleral depression is the recommended standard of care for assessment of flashes and floaters, residents in training may routinely use alternative techniques as a result of extrinsic and intrinsic factors. PMID- 28985805 TI - Antigen-specificity of antiretinal antibodies in patients with noninfectious uveitis. AB - OBJECTIVE: Antiretinal antibodies (ARAs) have previously been described in noninfectious uveitis. However, the antigen specificity of these ARAs has not been investigated. The purpose of this study was to identify antigen-specific ARAs in noninfectious uveitis. METHODS: A total of 18 patients with noninfectious uveitis were enrolled. Surface plasmon resonance was used to measure binding responses of patient and control sera against several uveitogenic proteins: recoverin, S-antigen, interphotoreceptor retinoid binding (IRBP), retinal-pigment epithelium-specific 65-kDa protein (RPE65), tyrosinase-related protein 1 (TRYP1), and tyrosinase-related protein 2 (TRYP2). RESULTS: The frequency of ARA positivity against S-antigen, IRBP, RPE65, TYRP1, and TYRP2 in patients with uveitis did not differ significantly from that of normal controls. However, ARA positivity for recoverin was more frequently observed in patients with uveitis (p = 0.002). A total of 10 patients in the uveitis cohort had birdshot chorioretinopathy, and all 10 were positive for anti-recoverin ARAs. CONCLUSIONS: Patients with noninfectious uveitis have increased frequency of ARA positivity against recoverin. This ARA deserves further investigations as a potential biomarker and pathogenic agent in noninfectious uveitis, especially in birdshot chorioretinopathy. PMID- 28985806 TI - Low-dose ranibizumab as primary treatment of posterior type I retinopathy of prematurity. AB - OBJECTIVE: The aim of this study was to evaluate the visual and structural outcomes of eyes that received ranibizumab as treatment for retinopathy of prematurity (ROP). METHODS: This was a retrospective case series of infants who received a 0.2 mg (0.02 mL) intravitreal injection of ranibizumab as the primary treatment for type 1 ROP. Outcome measures included regression or recurrence of ROP, complications of treatment, and assessment of visual acuity and refractive error. RESULTS: Forty-two eyes of 21 infants (13 male) were included. Mean gestational age and birth weight were 24.6 +/- 1.3 weeks and 613 +/- 91 g, respectively. Mean age at injection was 37.4 +/- 2.2 weeks postmenstrual age, and mean follow-up period was 10.1 +/- 7 months. Active neovascularization regressed rapidly, and anatomical outcomes were favourable in all eyes. Twelve eyes of 6 infants received supplemental laser photocoagulation at a mean post-menstrual age (PMA) of 72.0 +/- 27.3 weeks when vascularization had not advanced beyond zone II. Visual acuity was measurable in 28 of 42 eyes. Mean visual acuity was 0.94 +/ 0.36 logMAR. Mean spherical equivalent was +1.00. There were no ocular or systemic complications in these patients and no cicatricial complications were observed with no progression to stage 4 or 5 disease. CONCLUSIONS: A single intravitreal dose of 0.2 mg (0.02 mL) ranibizumab showed favourable anatomical and functional outcomes in eyes with type 1 ROP. PMID- 28985808 TI - Community vision screening in preschoolers: initial experience using the Plusoptix S12C automated photoscreening camera. AB - OBJECTIVE: Amblyopia is the leading cause of monocular vision impairment in children. Early intervention is critical to prevent permanent vision impairment. Preschool vision screening programs in Canada are limited. This study reports the initial results of a community-wide vision screening program for preschoolers using the Plusoptix S12C Photoscreener (Plusoptix Inc, Nuremburg, Germany). DESIGN: Cross-sectional. PARTICIPANTS: For this study, 1443 children aged 18-59 months were recruited and screened in various community settings in London, Ontario. METHODS: Participants were screened with the Plusoptix S12C device from September 2015 to May 2016. Data were analyzed for percentage of children referred for amblyogenic risk factors using the Arnold 2012 referral criteria. Referral, inconclusive results, follow-up rate, and positive predictive value were reported. RESULTS: Data from 1321 children were analyzed. Mean age of children meeting the inclusion criteria was 34.1 +/- 9.6 (18-58) months. One hundred and nineteen children were referred to an optometrist for a comprehensive eye exam; 39 (3.0%) were inconclusive screens. The referral rate for children detected with amblyogenic risk factors was 6.1%. Forty (50.0%) children were documented as complying with the follow-up examination. The positive predictive value was 81.8%. CONCLUSIONS: Our community-wide vision screening program identified in a timely, manner, 80 preschoolers with amblyogenic risk factors previously unknown to be present. Results identified children with amblyogenic risk factors that may have gone undetected. This program could serve as a model for consideration by policy makers. PMID- 28985807 TI - Age-related macular degeneration: is polypoidal choroidal vasculopathy recognized and treated? AB - OBJECTIVE: To assess how polypoidal choroidal vasculopathy (PCV) is recognized and treated, and to assess whether treatment outcomes are different between Chinese and Caucasian Canadian patients with age-related macular degeneration (AMD). DESIGN: Retrospective chart review. PARTICIPANTS: 154 eyes from 135 Chinese patients and 2291 eyes from 1792 Caucasian patients who were newly diagnosed with either AMD or PCV and had more than 1 year of follow-up were included. METHODS: All newly diagnosed AMD patients presenting to the Retina Service of 3 Toronto University Hospitals, between March 25, 2008, to September 30, 2014, were reviewed. RESULTS: 10/154 eyes (6.5%) in Chinese Canadians and 16/2291 eyes (0.7%) in Caucasian Canadians were diagnosed as having PCV. Indocyanine green angiography (ICGA) was used to diagnose PCV in 20% of Chinese Canadians and 8.8% of Caucasian Canadians. Clinical practices with a larger percentage of Chinese patients were more likely to diagnose PCV in both Chinese (p = 0.004) and Caucasian patients (p = 0.03), were more likely to use photodynamic therapy (PDT) (p < 0.01), and had significantly greater central retinal thickness decrease (p < 0.001). CONCLUSION: Our study has shown that PCV is under-recognized in a Canadian population, and ICGA is underutilized. In clinical practices with a greater portion of Chinese patients, PCV is more often recognized and PDT is used more liberally. PMID- 28985809 TI - A decade of surgical eye removals in Ontario: a clinical-pathological study. AB - OBJECTIVE: To assess patient demographics, clinical indications, and pathologic causes of surgically removed eyes over a decade in Ontario (Canada) and to identify areas of ocular disease management needing more attention. DESIGN: Retrospective cross-sectional study. PARTICIPANTS: The surgically removed eyes of 713 consecutive mainly adult patients from 2004 to 2013. METHODS: Demographic, clinical, and pathologic data were collected on all eyes received by the University of Toronto Ophthalmic Pathology Laboratory from 2004 to 2013. RESULTS: Of the 713 eyes removed, enucleations accounted for 60% of cases, eviscerations for 39% of cases, and exenteration for 1% of cases. The most common clinical indications for surgical eye removal were blind painful eye (37%), neoplasm (35%), and trauma (6%). The leading pathologic causes of eye removal were neoplasm (36%), glaucoma (21%), infection or inflammation (17%), and trauma (16%). Glaucoma-related findings were the most common pathologic findings observed (38%), regardless of the primary cause. CONCLUSIONS: A blind painful eye and neoplasms were the most commonly documented indications prior to removal of the eye. Common pathologies included glaucoma, neoplasms, infection/inflammation, and trauma. However, regardless of the primary cause, glaucoma-related pathologies were the most common pathologic findings. Refractory eye disease and pain continue to be important reasons for removal of eyes among patients in Ontario. More effective and targeted management strategies are needed to reduce the need for this radical eye surgery of last resort. PMID- 28985810 TI - Effectiveness of indocyanine green gel in the identification and complete removal of the medial wall of the lacrimal sac during endoscopic endonasal dacryocystorhinostomy. AB - OBJECTIVE: We investigated the effect of using indocyanine green (ICG) gel, a mixture of ICG and Viscoat, on complete removal of the medial wall of the lacrimal sac as well as the success rate of endoscopic endonasal dacryocystorhinostomy (DCR) for primary acquired nasolacrimal duct obstruction. METHODS: Consecutive cases of endoscopic endonasal DCR between January and December 2010 were included in a retrospective, comparative manner. A total of 91 patients with primary acquired nasolacrimal duct obstruction were enrolled. Surgical method was selected according to time period. In the ICG gel group, we used ICG gel, which is a fluorescent-colored viscoelastic substance made of ICG dye (25 mg) and Viscoat. ICG gel was injected into the lacrimal sac via the inferior canaliculus prior to lacrimal sac dissection. The anatomic and functional surgical success rates of endoscopic endonasal DCR in each group were compared. RESULTS: Our study included 49 cases in the ICG gel group and 42 cases in the control group. The functional success rate of endoscopic endonasal DCR reached 93.9% (46 of 49) in the ICG gel group compared with 71.4% (30 of 42) in the control group (Pearson's chi2 test, p value = 0.004). In contrast, there was no statistically significant correlation between use of ICG gel and anatomic success rate of endoscopic endonasal DCR. CONCLUSIONS: Using ICG gel during lacrimal sac dissection may enhance the functional success rate of endoscopic endonasal DCR for primary acquired nasolacrimal duct obstruction by facilitating easier identification and subsequent complete removal of the medial wall of the lacrimal sac. PMID- 28985811 TI - Ocular injury in orbital fractures at a level I trauma center. AB - OBJECTIVE: To determine the acuity of ophthalmology referral for orbital fractures. METHODS: This is a retrospective chart review of 73 cases of orbital fractures over a 1-year period at a level I trauma centre. All consultations including those for orbital fractures were included in the study. The age and sex of the patient, date and time of initial emergency room (ER) arrival, date and time of input of the ophthalmology consultation, date and time the patient actually saw ophthalmology, reasons for consultation, location of examination, mechanism, and ocular findings at initial and follow-up examination, and any orbital surgery performed were recorded. RESULTS: Of the 73 patients referred, 10 had an ocular abnormality on examination. Of the 65 routine referrals for orbital fracture received, 5 had an ocular abnormality on examination, whereas 5 of the 8 patients referred for an ocular abnormality in addition to the orbital fracture had an ocular abnormality, for an overall rate of 13.7%. Of the routine referrals, none had severe ocular injuries, such as globe rupture or retrobulbar hemorrhage, requiring immediate ocular intervention. CONCLUSIONS: Orbital fractures may be associated with severe ocular abnormalities, although routine cases of orbital fractures in the absence of suspicion of serious ocular injury may be less likely to have abnormalities requiring emergent evaluation by an ophthalmologist. A prospective study evaluating orbital fractures would help clarify this. PMID- 28985812 TI - Barriers to electronic medical record implementation: a comparison between ophthalmology and other surgical specialties in Canada. AB - OBJECTIVE: In the present study, the barriers limiting widespread adoption of electronic medical records (EMRs) among Canadian ophthalmologists were evaluated in comparison with physicians from other surgical specialities. The published literature regarding EMR use in ophthalmic practice was also reviewed. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: A total of 1199 Canadian surgeons participating in the 2014 National Physician Survey (NPS). METHODS: Data regarding speciality surgeons' adoption of EMR programs were extracted from the 2014 NPS, a nationwide survey of practicing physicians in Canada. The data were entered into a spreadsheet, and basic statistical analyses, including chi2 analyses, were performed to compare the responses of ophthalmologists to other surgeons. RESULTS: Compared with other surgeons, ophthalmologists surveyed were significantly more likely to identify the following barriers to EMR adoption: "no suitable product for my practice" (p = 0.01), "too costly" (p = 0.0006), "too time consuming" (p < 0.0001), and "planning to retire soon" (p = 0.001). No statistically detectable differences were found between ophthalmologists and other surgeons for the following barriers: privacy concerns, reliability concerns, and lack of training. CONCLUSIONS: The barriers that limit increased EMR adoption among Canadian ophthalmologists are different from those of other surgeons. This may be attributed to unique features of the field, including heavy reliance on hand-drawn figures in documentation, high patient volume, and the high costs associated with independent practice. Given the well-established benefits of EMR technology, consideration should be given to implementing strategies to mitigate these barriers. Additional research may help determine which specific improvements can be made to increase the use of EMR systems by ophthalmologists. PMID- 28985813 TI - Collagen cross-linking as an adjunct for repair of corneal lacerations: a cadaveric study. AB - OBJECTIVE: To determine the efficacy of collagen cross-linking (CXL) as an adjunct to suturing in the repair of corneal lacerations. METHODS: A cadaveric study was undertaken in which a linear 5 mm corneal laceration was created in the central cornea of 20 eyes. The eyes were then randomized to receive 1 (n = 8), 2 (n = 8), or 3 (n = 4) standard corneal sutures. The burst pressure of the wound was then measured. All eyes in the 1- and 2-suture group then underwent standard CXL, with burst pressure repeated afterward. RESULTS: The initial wound burst pressure in the 1-, 2-, and 3-suture groups was 54.9, 74.0, and 201.2 mm Hg, respectively. After CXL, wound burst pressure increased by a mean of 3.2 and 62.3 mm Hg in the 1- and 2-suture groups, respectively. This change was statistically significant in the 2-suture group (p = 0.017). After CXL, the 2-suture group still had a significantly lower burst pressure compared with the 3-suture group (p = 0.011). CONCLUSIONS: The study highlights a potential novel application for CXL to strengthen corneal wounds. Provided that suture density is sufficient to appose the wound edges, CXL may result in short-term wound strengthening. This could potentially allow for decreased corneal suture density and a corresponding decrease in suture-related complications. PMID- 28985814 TI - Tear osmolarity and subjective dry eye symptoms in migraine sufferers. AB - OBJECTIVE: Previous studies have suggested an association between dry eye and migraine. In a busy ophthalmologist clinic, quick identification of dry eye in migraine sufferers may improve their quality of life. Tear osmolarity is an objective and reliable tool for diagnosing dry eye. It has not been investigated in any population with migraine. Using tear osmolarity and questionnaires, we aimed to explore the relationship between dry eye and clinical symptoms in patients with migraine. DESIGN: Prospective cross-sectional study. PARTICIPANTS: Thirty-four adults with migraine sequentially recruited from a single neurologist's practice. METHODS: Patients were assessed for subjective and objective signs of migraine and dry eye by using the Migraine Disability Assessment Score, the Ocular Surface Disease Index, and tear osmolarity (TearLab). Headache characteristics were compared by using chi2, Fisher's exact, and Mann-Whitney U tests. Osmolarity scores were compared with scores for headache features. RESULTS: Median age of patients was 38 years, and 76.5% were females. Severe migraine disability was reported in 75.6%, and 34.5% reported moderate to severe dry eye symptoms. Objectively, 49.5% had evidence of dry eye, significantly higher than the 20% recognized in the general population (p < 0.0001). Aura was found to occur more frequently with dry eye (43.8% vs 5.9%; p = 0.02). Those with daily headaches were also more likely to have higher tear osmolarity with marginal significance (median osmolarity 310 mOsm/L vs 299 mOsm/L; p = 0.08). CONCLUSIONS: Patients with migraine, especially those with aura, appear more likely to have dry eye, as indicated by tear osmolarity. Tear osmolarity may also be greater in those who suffer from daily headaches. PMID- 28985815 TI - Young donor-graft assisted endothelial keratoplasty (PDEK/DMEK) with epithelial debridement for chronic pseudophakic bullous keratopathy. AB - OBJECTIVE: The aim of this study was to describe the applicability and report visual outcomes for the treatment of subepithelial fibrosis and anterior stromal scarring in cases of chronic pseudophakic bullous keratopathy (PBK) with epithelial debridement and endothelial keratoplasty (EK) (pre-Descemet endothelial keratoplasty [PDEK]; Descemet membrane endothelial keratoplasty [(DMEK]) using young donor tissue. DESIGN: Prospective, single-centre, interventional study. PARTICIPANTS: 6 cases with chronic PBK (> 1 year duration). METHODS: Case 1 underwent PDEK with glued intraocular lens (IOL) as a single stage procedure, whereas cases 2 and 3 underwent glued IOL followed by DMEK and PDEK, respectively, as a second-stage procedure. Cases 4 and 6 underwent PDEK, whereas case 5 underwent DMEK. Epithelial debridement was performed in all cases at the time of EK, and young donor grafts were used. The main outcome measures were best spectacle-corrected visual acuity, clearance of corneal scar and haze, central corneal thickness (CCT), specular microscopy, and endothelial cell count (ECC). RESULTS: Postoperatively, all cases demonstrated significant improvement in visual acuity. The mean value of depth of subepithelial haze was 121+/-71.7 um and 25.3 +/- 19.8 um in the preoperative and postoperative periods, respectively (p = 0.028). At the 1-month follow-up, the mean preoperative CCT of 676 +/- 92.7 um was reduced to 534.6 +/- 21.1um. At the 6-month follow-up, the mean ECC loss resulting from the procedure was 36.5 +/- 10.4%. CONCLUSIONS: EK with epithelial debridement performed for the treatment of chronic PBK resulted in significantly improved visual acuity to a functional level, with the clearance of subepithelial fibrosis and anterior stromal scar, in most patients. PMID- 28985816 TI - Infantile cataract: comparison of two surgical approaches. AB - OBJECTIVE: To compare the results of 2 cataract extraction techniques with primary intraocular lens (IOL) implantation in children. DESIGN: Retrospective comparative case series study. METHODS: This study included children with congenital or developmental cataract. In all cases, anterior capsulorhexis, lens aspiration, posterior continuous curvilinear capsulorhexis, and primary IOL implantation were performed. We compared 2 surgical approaches. In the first approach, after IOL implantation in the bag, posterior optic capture (OC) was performed without anterior vitrectomy (OC technique); in the second approach, anterior vitrectomy was performed without OC of the IOL (AV technique). Patient demographic data as well as ethnic origin, child's age at cataract diagnosis, child's age at surgery, axial length, IOL power in diopters, visual acuity, visual axis opacification, and complications were assessed. RESULTS: One hundred twenty-three eyes were included for surgical approach outcomes comparison; 21 eyes underwent the OC surgical approach and 102 the AV surgical approach. The mean patient age at surgery was 57.3 +/- 47.1 months. The mean follow-up was 63.13 months (range 12-202 months). Epithelial lens reproliferation was the major adverse event in our series, affecting 21.1% of patients' eyes; the mean time to epithelial lens reproliferation development was 90 +/- 9.70 months. There was no statistically significant difference between the two groups in best spectacle corrected visual acuity or epithelial lens reproliferation incidence. CONCLUSIONS: In our case series we did not find any difference between surgical techniques. PMID- 28985817 TI - Nutritional optic neuropathy instead of tobacco-alcohol amblyopia. PMID- 28985818 TI - Pull-through technique for delivery of a larger diameter DMEK graft using endothelium-in method. PMID- 28985819 TI - Subconjunctival injection of bevacizumab for recurrent conjunctival papilloma: a case report. PMID- 28985820 TI - Ciliochoroidal detachment following pure sulfur hexafluoride injection in Descemet stripping automated endothelial keratoplasty. PMID- 28985821 TI - Persistent pediatric primary canaliculitis associated with congenital lacrimal fistula. PMID- 28985822 TI - Mooren's ulcerative keratitis after systemic pegylated interferon alpha2a in chronic hepatitis C. PMID- 28985823 TI - Eye drop safety seal causing ocular irritation following cataract and vitrectomy surgery. PMID- 28985824 TI - Optic nerve hypoplasia in a patient with a de novo KIF1A heterozygous mutation. PMID- 28985825 TI - Childhood glaucoma in neonatal Marfan syndrome resulting from a novel FBN1 deletion. PMID- 28985827 TI - Ethambutol optic neuropathy associated with enhancement at the optic chiasm. PMID- 28985826 TI - Optic nerve hypoplasia and internal carotid artery hypoplasia: a new association. PMID- 28985828 TI - Cerebellopontine angle astrocytoma producing Bruns nystagmus mimicking vestibular schwannoma. PMID- 28985829 TI - Case series: Merkel cell carcinoma of the eyelid. PMID- 28985830 TI - Haller cells: A risk factor for spontaneous orbital floor fracture? PMID- 28985831 TI - Immunoglobulin G4-related dacryocystitis. PMID- 28985832 TI - Chandelier scleral buckling for retinal detachment in Stevens-Johnson syndrome. PMID- 28985833 TI - Intraretinal macular hemorrhage due to high-power handheld blue laser. PMID- 28985834 TI - An unusual presentation of Roth spots in Cogan's syndrome. PMID- 28985835 TI - Palliative therapy for stage IV rectal adenocarcinoma: how frequently is it used? AB - BACKGROUND: Palliative care is associated with decreased cost and improved quality of life, although its use in stage IV rectal cancer is understudied. MATERIALS AND METHODS: Stage IV rectal cancer patients (2004-2011) who did not undergo surgery with curative intent were identified within the National Cancer Database. Patients receiving palliative therapy were stratified by the type of intervention, as were patients undergoing chemotherapy that was not designated as palliative. Logistic regression was used to identify factors associated with the receipt of palliative therapy. RESULTS: A total of 11,245 patients were analyzed, of which 2314 (20.6%) received palliative therapy. Use of palliative therapy as a category of treatments did not change significantly from 2004-2012 (19.4%-23.0%; P = 0.14), but the use of palliative chemotherapy nearly doubled (4.7%-8.7%; P < 0.001). Factors associated with the use of palliative therapy included age >60 y and increasing chronic comorbidities; these subgroups also had lower odds of receiving chemotherapy that was not designated as palliative. Differences in gender and race were not associated with variations in the receipt of palliative therapy. CONCLUSIONS: For stage IV rectal cancers managed without curative intent, use of palliative therapies remains consistently low, with a preference for sicker patients. PMID- 28985837 TI - Patient-reported quality of life after bariatric surgery: a single institution analysis. AB - BACKGROUND: Bariatric surgery is an effective weight loss and comorbidity treatment among severely obese patients. However, there are limited data describing its impact on patient-reported quality of life (QoL). We examined patient-reported QoL after bariatric surgery and analyzed variables associated with higher postoperative QoL. METHODS: Patient demographics, comorbidities, and weight loss data were obtained from our institutional database for patients who underwent bariatric surgery from January 2010 to December 2012. QoL scores were obtained during preoperative and postoperative visits (2, 6, 12, 24, 52, and 104 wk) from the Moorehead-Ardelt Quality of Life Questionnaire II. Multivariable logistic regression was performed to generate odds ratios for variables hypothesized a priori to be associated with higher postoperative QoL. RESULTS: A total of 209 patients were included in the study. Patients lost an average of 59.1% (+/-19.0) of excess body weight 1 y after surgery. One-year postoperative QoL scores were available for 42% of patients. Mean QoL scores improved from 0.82 preoperatively to 1.66 1 y postoperatively (P = 0.004). Patients scored higher in all individual areas of Moorehead-Ardelt Quality of Life Questionnaire II: self esteem (0.22 versus 0.36), physical activity (0.11 versus 0.31), social life (0.28 versus 0.36), work ability (0.07 versus 0.22), sexual functioning (0.04 versus 0.16), and approach to food (0.11 versus 0.26; all P values <0.05). On multivariable analysis, higher QoL was associated with private insurance/self-pay versus Medicare (odds ratio 4.20 [95% confidence interval 1.39-12.68]). CONCLUSIONS: Bariatric surgery patients experienced significant improvement in QoL 1 y after surgery. Identifying modifiable predictors of high QoL after bariatric surgery requires additional investigation. PMID- 28985836 TI - A meta-analysis of implant-based breast reconstruction and timing of adjuvant radiation therapy. AB - BACKGROUND: Implant-based breast reconstruction is the most common type of reconstruction after postmastectomy radiation therapy (PMRT). The impact of the timing of PMRT to a tissue expander or permanent implant is not well understood. The purpose of this systematic review was to evaluate outcomes in implant-based reconstruction and the timing of PMRT. METHODS: A review of the English literature in the PubMed/MEDLINE database (2000-2016) was performed to identify all articles on implant-based breast reconstruction and PMRT. Cases from each study were grouped by PMRT to a tissue expander or PMRT to a permanent implant. Outcomes of interest included reconstructive failure and capsular contracture as overall rates and associations were pooled. Effect sizes (z values), risk ratios (RRs), and heterogeneity scores (I2) were calculated on meta-analysis. RESULTS: There were 20 studies meeting inclusion criteria with 2348 patients identified. Pooled analysis revealed an overall rate of reconstructive failure of 17.6% and Baker grade III/IV capsular contracture of 37.5%. PMRT applied to tissue expanders resulted in higher rates of reconstructive failure compared with PMRT applied to permanent silicone implants (20% versus 13.4%, RR = 2.33, P = 0.0083, 95% confidence interval 1.24-4.35), but lower rates of capsular contracture (24.5% versus 49.4%, RR = 0.53, P = 0.083, 95% confidence interval 0.26-1.09). CONCLUSIONS: Regardless of timing, PMRT applied to implant-based breast reconstruction was associated with high risk of reconstructive failure and capsular contracture. Surgeons should consider alternative strategies, such as autologous tissue reconstructions, in patients requiring PMRT. PMID- 28985838 TI - T3 versus T4 thoracoscopic sympathectomy for palmar hyperhidrosis: a meta analysis and systematic review. AB - BACKGROUND: Palmar hyperhidrosis (PH) is a benign sympathetic disorder that can adversely affect the quality of life of patients. Thoracic sympathectomy (TS) at the T3 or T4 level has been used to treat PH. We aimed to determine the optimal denervation level for TS by comparing the efficacy of T3 TS versus T4 TS in PH patients. METHODS: We searched the PubMed, Ovid MEDLINE, EMBASE, Web of Science, ScienceDirect, the Cochrane Library, Scopus, and Google Scholar databases for studies comparing T3 versus T4 TS for PH. Clinical end points included symptom resolution, patient satisfaction, and complications. RESULTS: Of 2201 articles reviewed, 10 (T3 group, 566 patients; T4 group, 629 patients) were selected. T4 TS was associated with a lower incidence of postoperative compensatory sweating, dry hands, and gustatory sweating than T3 TS. No significant difference in symptom resolution or patient satisfaction was found between the T3 and T4 groups. CONCLUSIONS: T4 TS may be superior to T3 TS in patients with PH. However, this finding should be validated in high-quality, large-scale randomized controlled trials. PMID- 28985839 TI - Peritoneal drainage is associated with higher survival rates for necrotizing enterocolitis in premature, extremely low birth weight infants. AB - BACKGROUND: To evaluate peritoneal drainage (PD) and laparotomy +/- resection/ostomy (LAP) as initial approaches to the surgical management of necrotizing enterocolitis (NEC) in premature, extremely low birth weight (ELBW) infants. METHODS: Kids' Inpatient Database (2003-2012) was searched for cases of NEC (International Classification of Diseases, ninth revision, Clinical Modification [ICD-9-CM] 777.5x) in premature (<37 weeks), extremely low birth weight (<1000 g) infants. Infants were admitted at <28 days of life. Propensity score (PS)-matched analyses were performed, using end points of hospital mortality, length of stay (LOS), and cost of hospitalization. Cases were matched 1:1 on 48 confounding variables (demographic, clinical, and hospital characteristics and 39 comorbidities). RESULTS: On PS-matched comparison, PD had higher survival versus LAP, P = 0.0009. LOS and cost were higher for PD versus LAP, P < 0.003. Survival rates did not differ between PD + LAP and PD-only treatments. LOS and cost were higher for PD + LAP versus PD-only, P < 0.02. PD + LAP infants had higher survival versus LAP, P = 0.0193. LOS and cost were higher for PD + LAP, P < 0.005. CONCLUSIONS: A risk-adjusted PS-matched analysis of operative management in premature, ELBW infants with NEC found higher survival rates associated with PD placement versus LAP, whether PD was used as definitive treatment or with subsequent LAP even after controlling for potential contributors to selection bias (i.e., stability influencing management preference). PMID- 28985840 TI - Near-infrared-conjugated humanized anti-carcinoembryonic antigen antibody targets colon cancer in an orthotopic nude-mouse model. AB - BACKGROUND: The success of a curative surgery for cancer is dependent on the complete removal of all cancer cells. Tumor visualization by the surgeon can be enhanced through fluorescent-antibody targeting. To further develop such technology, we selected humanized anti-carcinoembryonic antigen (CEA) conjugated to a near-infrared dye to target orthotopically-implanted human colon cancer in nude mice. MATERIALS AND METHODS: The HT-29 human colon cancer cell line was grown in culture and subcutaneously injected in mice. After 3 wk of growth, tumors were resected and cut into 2 mm3 fragments that were sutured to the cecum of five additional nude mice for orthotopic implantation. The tumors were allowed to grow for 4 wk at which point 3 had successful orthotopic tumor growth and were selected for injection of the humanized anti-CEA antibody conjugated to the near infrared dye IRDye800CW (anti-CEA-IRDye800CW). The antibody-dye conjugate (75 MUg) was administered via tail vein injection. Images were obtained with the Pearl Trilogy Small Animal Imaging System with both 700 and 800 nm channels and evaluated using Image Studio. RESULTS: Laparotomy was performed 24 h after labeling the tumors. When imaged through the 800 nm channel, the tumors were observed to be strongly labeled with anti-CEA-IRDye800. At 48 h, laparotomy was repeated which again demonstrated strong labeling of the tumors through the 800 nm channel, but with a lower absolute intensity (in relative units), than at 24 h. CONCLUSIONS: Humanized anti-CEA-IRDye800CW can rapidly and effectively label CEA-expressing human colon cancer in an orthotopic nude mouse model. Given the ability of this technology to target and label tumors with great specificity, the anti-CEA-IRDye800CW is currently being developed for clinical use in fluorescence guided surgery. PMID- 28985841 TI - Surgical resident technical skill self-evaluation: increased precision with training progression. AB - BACKGROUND: Surgical resident ability to accurately evaluate one's own skill level is an important part of educational growth. We aimed to determine if differences exist between self and observer technical skill evaluation of surgical residents performing a single procedure. MATERIALS AND METHODS: We prospectively enrolled 14 categorical general surgery residents (six post graduate year [PGY] 1-2, three PGY 3, and five PGY 4-5). Over a 6-month period, following each laparoscopic cholecystectomy, residents and seven faculty each completed the Objective Structured Assessment of Technical Skills (OSATS). Spearman's coefficient was calculated for three groups: senior (PGY 4-5), PGY3, and junior (PGY 1-2). Rho (rho) values greater than 0.8 were considered well correlated. RESULTS: Of the 125 paired assessments (resident-faculty each evaluating the same case), 58 were completed for senior residents, 54 for PGY3 residents, and 13 for junior residents. Using the mean from all OSATS categories, trainee self-evaluations correlated well to faculty (senior rho 0.97, PGY3 rho 0.9, junior rho 0.9). When specific OSATS categories were analyzed, junior residents exhibited poor correlation in categories of respect for tissue (rho 0.5), instrument handling (rho 0.71), operative flow (rho 0.41), use of assistants (rho 0.05), procedural knowledge (rho 0.32), and overall comfort with the procedure (rho 0.73). PGY3 residents lacked correlation in two OSATS categories, operative flow (rho 0.7) and procedural knowledge (rho 0.2). Senior resident self-evaluations exhibited strong correlations to observers in all areas. CONCLUSIONS: Surgical residents improve technical skill self-awareness with progressive training. Less-experienced trainees have a tendency to over-or underestimate technical skill. PMID- 28985842 TI - Increased population of immature enteric glial cells in the resected proximal ganglionic bowel of Hirschsprung's disease patients. AB - BACKGROUND: Enteric glial cells are essential for normal gastrointestinal function. Abnormalities in glial structure, development, or function lead to disturbances in gastrointestinal physiology. Fatty acid-binding protein 7 (FABP7) is a marker of immature enteric glial cells, whereas S100 is expressed only by mature glial cells. Patients with Hirschsprung's disease (HSCR) often suffer from dysmotility and enterocolitis despite proper surgery. We designed this study to determine the distribution and expression of glial cells in patients with HSCR compared to normal controls. METHODS: We investigated FABP7, S100, and PGP 9.5 expressions in both the ganglionic and aganglionic bowel of patients with HSCR (n = 6) versus normal control colon (n = 6). Protein distribution was assessed by using immunofluorescence and confocal microscopy. Gene and protein expressions were quantified using quantitative real-time polymerase chain reaction (qPCR), Western blot analysis, and densitometry. RESULTS: qPCR and Western blot analysis demonstrated a significantly increased FABP7 expression in ganglionic specimens compared to control specimen (P < 0.05). Confocal microscopy revealed FABP7+ glia cells lie under the colonic epithelium and in close apposition to enteric neurons in the ganglionic bowel. CONCLUSIONS: The significantly increased number of immature enteric glial cells (EGCs) in the ganglionic bowel of HSCR patients may have adverse effect on the function of enteric neurons and intestinal barrier and thus predispose these patients to intestinal motility problems and enterocolitis. PMID- 28985844 TI - Assessment of hemodynamic response to fluid resuscitation of patients with intra abdominal sepsis in low- and middle-income countries. AB - BACKGROUND: Patients with intra-abdominal infections need to achieve adequate hemodynamic status before being taken to the operating room. Multiple parameters (urinary output [UOP], vital signs, inferior vena cava collapsibility index, and central venous pressure) may be used to assess hemodynamic response to fluid resuscitation, but the options are few in limited-resource settings. This study aimed at assessing if a bedside-performed ultrasound to assess the inferior vena cava collapsibility index is superior to UOP in assessing hemodynamic response to fluid resuscitation. METHODS: All adult patients presenting to a tertiary referral hospital in the capital city of Rwanda with intra-abdominal infection requiring intravenous fluid (IVF) resuscitation before operation were included in this study. Before IVF administration, the baseline inferior vena cava collapsibility index (IVC-CI) and vital parameters were recorded. After initiation of IVF resuscitation, serial measurements of IVC-CI and UOP were recorded every 2 h until the decision was made to take the patient to the operating room. RESULTS: Twenty-four patients were enrolled. The mean duration of symptoms was 4.7 days. Four patients (16%) had altered mental status as a presenting symptom. Half of all patients had generalized peritonitis due to gangrenous bowel as the primary diagnosis (n = 12). The mean difference between time of hemodynamic response based on IVC-CI versus UOP was 2 h (P < 0.001). CONCLUSIONS: Measurement of the IVC-CI can provide early detection of hemodynamic response to fluid therapy in patients with intra-abdominal infection with spontaneous breathing compared to UOP. Future research should utilize this parameter in the preoperative management of hemodynamically unstable patients. PMID- 28985843 TI - Total parenteral nutrition in patients following pancreaticoduodenectomy: lessons from 1184 patients. AB - BACKGROUND: Total parenteral nutrition (TPN) has historically been used conservatively in the management of patients after pancreaticoduodenectomy (PD). Herein, we evaluate the indications for and outcomes associated with TPN use in a high-volume pancreatic surgery center. MATERIALS AND METHODS: We retrospectively queried our institution's pancreatic surgery database for patients who received TPN after PD from 2006 through 2015. RESULTS: Of 1184 patients who underwent PD, 232 (19.6%) received TPN perioperatively. The most common indications for TPN were delayed gastric emptying (DGE, n = 171, 73.7%), pancreatic fistula (n = 102, 44%), and generalized malnutrition (n = 25, 10.8%). The median day of TPN initiation was postoperative day 4 (range: -31 to 22), with a median usage of 9 days (range: 1-115). Forty-four (19%) patients received short-course TPN (<=3 days), primarily those diagnosed with isolated grade A DGE without associated complications (P = 0.0003). Multivariate analysis suggests the presence of deep surgical site infection (odds ratio: 3.09, [1.16-5.06], P = 0.018) or pancreatic fistula (odds ratio: 2.57, [1.03-6.41], P = 0.043) at the time of DGE presentation as predictive of long-term TPN requirement. Hyperglycemia (34.5%) was the most common complication resulting from TPN use, whereas central line associated bloodstream infections (2.6%) were rare. Readmissions (35.3% TPN cohort; 15% historical institutional rate) were most commonly due to poor oral intake (26.8%). The 30-day mortality rate in the overall TPN cohort was 3.4% (0.8% historical institutional rate). CONCLUSIONS: TPN is a critical and safe adjunct for patients who develop PD-associated complications; however, it may be of limited utility for patients with isolated DGE. PMID- 28985845 TI - Postoperative paralytic ileus remains a problem following surgery for advanced pelvic cancers. AB - BACKGROUND: Paralytic postoperative ileus (POI) is associated with increased morbidity and mortality after abdominal surgery. Despite increased awareness and implementation of various measures, POI remains a problem, perhaps moreso for those patients undergoing extensive oncological surgical treatment. The aim of this study was to describe the extent of POI after advanced cancer surgery in the era of contemporary treatment modalities of POI. METHODS: A retrospective analysis of all patients who underwent either abdominoperineal excision with transpelvic vertical rectus abdominal musculocutaneous (VRAM)-flap after anal cancer or pelvic exenteration at single institution from January 2012 to November 2013 was carried out. Patients were identified from operative codes, and data were retrieved from patient records. RESULTS: Eighty-nine patients were included in the study, 21 abdominoperineal excision and 68 pelvic exenteration procedures. Median nasogastric tube duration was 4 days (range: 0-44). Median time to first flatus was 1 day (range 0-15). Median time to defecation was 3 days (range 0-16 days). Twenty-three patients (28%) experienced prolonged ileus. There was a significant longer time to first defecation for patients who received a VRAM flap (P = 0.046). There was also a significant association between longer operative times and first flatus (P = 0.007). CONCLUSIONS: This retrospective study reveals that POI remains as a significant clinical problem in patients undergoing advanced pelvic cancer surgery, despite the increased awareness and implementation of enhanced recovery protocols. New regimens for better prophylaxis are needed, and further research on POI treatment is important. PMID- 28985846 TI - Assessment of clinical feedback given to medical students via an electronic feedback system. AB - BACKGROUND: The feedback medical students receive during clinical rotations, traditionally verbal and not formally captured, plays a critical role in student development. This study evaluates written daily feedback given to students through a novel web-based feedback system. METHODS: A Minute Feedback System was used to collect feedback given to medical students during their surgery clerkship from May 2015-April 2016. Using qualitative content analysis, feedback comments were categorized as: encouraging, corrective, specific, and nonspecific. Effective feedback was a combination of specific and either corrective or encouraging feedback; ineffective feedback contained only nonspecific comments; mediocre feedback contained elements of both effective and ineffective comments. RESULTS: 3191 feedback requests were sent by medical students and 2029 faculty/resident feedback responses were received. The overall response rate was 62%. Nonspecific feedback comprised 80% of faculty, 83% of senior resident, and 78% of junior resident comments. Specific feedback was given by only 35% of faculty, 17% of senior residents, and 26% of junior residents. Faculty provided Effective feedback in only 16% of comments, senior residents 8%, and junior residents 17%. Mediocre feedback comprised 13% of faculty, 9% of senior resident, and 7% of junior resident comments. Ineffective feedback comprised 67% of all feedback: 60% of faculty, 72% of senior resident, and 68% of junior resident feedback. CONCLUSIONS: The majority of resident and faculty feedback to medical students using an electronic, email-based application during their surgery clerkship was nonspecific and encouraging and therefore of limited effectiveness. This presents an opportunity for resident/faculty development and education regarding optimal feedback techniques. PMID- 28985847 TI - Discordance of conflict of interest self-disclosure and the Centers of Medicare and Medicaid Services. AB - BACKGROUND: The Open Payments Database (OPD) discloses financial transactions between manufacturers and physicians. The concordance of OPD versus self-reported conflicts of interest (COI) is unknown. MATERIALS AND METHODS: Our objectives were to compare (1) industry and self-disclosed COI in clinical literature, (2) payments within each disclosure level, and (3) industry- and self-disclosed COI and payments by specialty. This was an observational study. PubMed was searched for clinical studies accepted for publication from January 2014 to June 2016. Author and OPD-disclosed COIs were compared. Articles and authors were divided into full disclosure, incomplete industry disclosure, incomplete self-disclosure, and no COI. Primary outcome (differences in reported COI per article) was assessed using McNemar's test. Payment differences were compared using Kruskal Wallis test. RESULTS: OPD- and self-disclosed COI differed (65.0% discordance rate by article, P < 0.001). Percentages of authors within each disclosure category differed between specialties (P < 0.001). Hematology articles exhibited the highest discordance rate (79.0%) and received the highest median payment for incomplete self-disclosure ($30,812). CONCLUSIONS: Significant discordance exists between self- and OPD-reported COI. Additional research is needed to determine reasons for these differences. PMID- 28985848 TI - Transforming growth factor beta1 and Fas ligand synergistically enhance immune tolerance in dendritic cells in liver transplantation. AB - BACKGROUND: Long-term survival of patients following liver transplantation can be achieved by application of genetically modified, immune tolerogenic immature dendritic cells (imDCs) to overcome allograft-induced acute cellular rejection, a major cause of death. In this study, using a rat model of liver transplantation, we determined whether cotransfection of transforming growth factor beta1 (TGF beta1) and Fas ligand (FasL) in imDCs synergistically enhances immune tolerance. MATERIALS AND METHODS: We first determined the immune tolerogenic effects of TGF beta1 and FasL independently or together in imDCs by measuring the levels of CD86 and CD80 and by assessing T-cell proliferation using mixed lymphocyte reaction tests. Next, a rat model of liver transplantation, in which dark agouti and Lewis rats treated with DCs exogenously expressing TGF-beta1 and/or FasL served as donors and recipients, respectively, was used to examine TGF-beta1/FasL-induced immune tolerance. Specifically, we assessed the Banff rejection activity index (RAI), liver functions (alanine transaminase and total bilirubin levels), serum levels of interleukin (IL)-1, IL-10, and IL-12, apoptosis by TUNEL, and posttransplant survival. RESULTS: TGF-beta1/FasL cotransfection of imDCs resulted in greater reduction of CD85 and CD80 expression and T-cell proliferation than a monotransfection. Cotransfected imDCs also showed reduced RAI scores, decreased plasma alanine transaminase and total bilirubin, altered cytokine levels, increased apoptosis, and prolonged survival than monotransfected imDCs in liver allografted rats. CONCLUSIONS: By enhancing immune tolerance, reducing liver damage, and achieving long-term postsurgery survival, TGF-beta1/FasL cotransfection of imDCs may prove more beneficial for patients undergoing liver transplantation. PMID- 28985849 TI - Treating a 20 mm Hg gradient alleviates myocardial hypertrophy in experimental aortic coarctation. AB - BACKGROUND: Children with coarctation of the aorta (CoA) can have a hyperdynamic and remodeled left ventricle (LV) from increased afterload. Literature from an experimental model suggests the putative 20 mm Hg blood pressure gradient (BPG) treatment guideline frequently implemented in CoA studies may permit irreversible vascular changes. LV remodeling from pressure overload has been studied, but data are limited following correction and using a clinically representative BPG. MATERIALS AND METHODS: Rabbits underwent CoA at 10 weeks to induce a 20 mm Hg BPG using permanent or dissolvable suture thereby replicating untreated and corrected CoA, respectively. Cardiac function was evaluated at 32 weeks by magnetic resonance imaging using a spoiled cine GRE sequence (TR/TE/FA 8/2.9/20), 14 * 14 cm FOV, and 3-mm slice thickness. Images (20 frames/cycle) were acquired in 6-8 short axis views from the apex to the mitral valve annulus. LV volume, ejection fraction (EF), and mass were quantified. RESULTS: LV mass was elevated for CoA (5.2 +/- 0.55 g) versus control (3.6 +/- 0.16 g) and corrected (4.0 +/- 0.44 g) rabbits, resulting in increased LV mass/volume ratio for CoA rabbits. A trend toward increased EF and stroke volume was observed but did not reach significance. Elevated EF by volumetric analysis in CoA rabbits was supported by concomitant increases in total aortic flow by phase-contrast magnetic resonance imaging. CONCLUSIONS: The indices quantified trended toward a persistent hyperdynamic LV despite correction, but differences were not statistically significant versus control rabbits. These findings suggest the current putative 20 mm Hg BPG for treatment may be reasonable from the LV's perspective. PMID- 28985850 TI - The administration of argon during ex vivo normothermic perfusion in an experimental model of kidney ischemia-reperfusion injury. AB - BACKGROUND: Argon has shown potential as an organoprotective agent in numerous models of ischemia-reperfusion injury (IRI). The aim of this study was to evaluate the effects of argon gas during ex vivo normothermic perfusion (EVNP) in an experimental porcine model of kidney IRI. MATERIALS AND METHODS: After a warm ischemia time of 15 min and 17 h of static cold storage, porcine kidneys underwent 1 h of EVNP using leukocyte-depleted blood. During EVNP, kidneys were perfused with a gas composition either of 70% argon (n = 6), 70% nitrogen control (n = 6), or standard 95% oxygen (n = 6) balanced with 5% carbon dioxide. After EVNP, kidneys were reperfused with whole blood under standard conditions for 3 h to assess renal function and injury. RESULTS: During 1-h EVNP, the mean renal blood flow was numerically higher in the argon group (49.2 +/- 16.2 mL/min/100 g; P = 0.320) compared with the nitrogen and oxygen groups (42.9 +/- 18.64 and 37.71 +/- 7.0 mL/min/100 g, respectively). Other measures of renal function and hemodynamics were not significantly different between the argon and control groups during this period. During reperfusion, no significant differences were found in functional parameters or inflammatory markers (P < 0.05). Histologic analysis revealed no significant change in morphology or hypoxia-inducible factor 1 alpha staining between gaseous groups. Nuclear hypoxia-inducible factor-1 alpha staining was observed only after 3 h of reperfusion. CONCLUSIONS: Our findings suggest that using 70% argon during 1 h of EVNP does not mediate a measurable organoprotective effect in an experimental porcine model of IRI. PMID- 28985851 TI - In-bag enzymatic splenic digestion: a novel alternative to manual morcellation? AB - BACKGROUND: Contained in-bag spleen morcellation is a conventional extraction technique for safe spleen removal during laparoscopic splenectomy. Existing data for the use of in-bag enzymatic splenic digestion as an alternative to morcellation are lacking. This proof-of-concept study sought to evaluate the effectiveness of single and combinatorial enzyme digestion of murine spleens. MATERIALS AND METHODS: Murine spleens were digested with collagenase alone or with combinations of commercially available enzymes (collagenase, elastase, hyaluronidase, neutral protease) to determine their degradation effect. The primary end point was the percentage of mass reduction at 15 and 30 min. RESULTS: For collagenase alone (n = 15), the mean reduction in mass was 14 +/- 10% (range: 2%-31%) at 15 min and 30 +/- 25% (range: 7%-100%) at 30 min. Using combinatorial dissolution with collagenase, hyaluronidase, and elastase (n = 8), the mean reduction in mass was 27 +/- 16% (range: 6%-42%) at 15 min and 48 +/- 27% (range: 3%-100%) at 30 min. Injecting the enzyme solution into whole spleens (n = 9) yielded a mean reduction in mass of 22 +/- 13% (range: 9%-42%) at 15 min and 55 +/- 31% (range: 9%-100%) at 30 min; mean reduction was 9 +/- 13% (range: 0%-39%) at 15 min and 23 +/- 13% (range: 3%-53%) with no injection (n = 12). CONCLUSIONS: We provide the first demonstration of successful enzymatic murine spleen digestion as an alternative method for in-bag spleen removal during laparoscopic splenectomy. However, the significant cost and quantities of commercial enzyme required for clinical application dampens the enthusiasm for this novel approach. PMID- 28985852 TI - Development of a total colectomy and ileorectal anastomosis rat model to evaluate colonic metaplasia. AB - BACKGROUND: Ulcerative colitis is an idiopathic inflammatory condition of the colon that may require surgical intervention including proctocolectomy and either ileal pouch-anal anastomosis or in the pediatric population, low ileorectal anastomosis (IRA). Often, subsequent physiologic alteration (or colonic metaplasia) occurs in the anastomosed small bowel that includes changes in mucin content, villous blunting, and increased expression of WNT5A, a marker of colonic crypt regeneration. We developed a rat low IRA model to assess and study the development of colonic metaplasia. MATERIALS AND METHODS: We subjected male Sprague-Dawley rats (n = 17) to total colectomy and low IRA surgery and evaluated healing periodically by endoscopic evaluation. The ileum upstream of the anastomosis was assessed by hematoxylin and eosin staining, and the mucin content was measured by high iron diamine-Alcian blue staining. Wnt5a transcripts were quantified by reverse transcription and quantitative polymerase chain reaction at the 8-wk study end point. RESULTS: Although no gross endoscopic evidence of inflammation was seen throughout the course of the study, colonic metaplasia in the small bowel was detected in 7 out of 10 (70%) rats at the study end point. In rats with colonic metaplasia, enhanced expression of Wnt5a was evident at the study end point compared to levels in the terminal ileum at the time of surgery. CONCLUSIONS: Within 4-8 wk, the majority of rats subjected to IRA developed colonic metaplasia defined by villous blunting, changes in mucin content, and increased expression of Wnt5a. This model provides a method to study small bowel colonic metaplasia. PMID- 28985853 TI - The falciform ligament as a graft for portal-superior mesenteric vein reconstruction in pancreatectomy. AB - BACKGROUND: Tumor invasion or adherence to the portal vein-superior mesenteric vein (PV/SMV) may be encountered during pancreatic surgery. In such cases, venous resection and reconstruction might be required for complete resection of the tumor. We report an innovative technique in which the graft for PV/SMV reconstruction was made with the falciform ligament. METHODS: Between May 2011 and July 2016, PV/SMV reconstruction with a falciform ligament graft was performed in 10 cases during pancreatectomy. Among these cases, including six cases with a patch graft and four cases with a conduit graft. Retrospective reviews of medical records and radiologic studies were performed. RESULTS: Ten patients with pancreatobiliary cancer underwent en bloc tumor resection with concurrent PV/SMV resection and reconstruction with a falciform ligament graft. There were six males and four females, and the mean age was 65.3 +/- 9.4 (48-80) y. Using Doppler ultrasound examination, all 10 grafts were shown to be patent at postoperative 2 wk. However, occlusion was found in one case with conduit graft and stenosis in the other three cases with conduit graft using enhanced computed tomography at postoperative 2 mo. Complete patency was shown in three of six cases with patch graft and stenosis in the other three cases at 2 mo after the operation. Although occlusion or stenosis of the grafts was observed, no severe adverse events occurred, and normal liver function was discovered in all 10 cases at postoperative 2 mo. CONCLUSIONS: Falciform ligament grafts might be considered for reconstruction of PV/SMV in the absence of appropriate vascular grafts. PMID- 28985854 TI - Reduced disparities and improved surgical outcomes for Asian Americans with colorectal cancer. AB - BACKGROUND: Studies suggest Asian Americans may have improved oncologic outcomes compared with other ethnicities. We hypothesized that Asian Americans with colorectal cancer would have improved surgical outcomes in mortality, postoperative complications (POCs), length of stay (LOS), and readmissions compared with other racial/ethnic groups. METHODS: We queried the 2011-2014 American College of Surgeons National Surgical Quality Improvement Program for patients who underwent surgery for colorectal cancer and stratified patients by race. Primary outcome was 30-d mortality with secondary outcomes including POCs, LOS, and 30-d readmission. Stepwise backward logistic regression analyses and incident rate ratio calculations were performed to identify risk factors for disparate outcomes. RESULTS: Of the 28,283 patients undergoing colorectal surgery for malignancy, racial/ethnic groups were divided into Caucasian American (84%), African American (12%), or Asian American (4%). On unadjusted analyses, compared with other racial/ethnic groups, Asian Americans were more likely to have normal weight, not smoke, and had lower American Society of Anesthesiologists score of 1 or 2 (P < 0.001). Postoperatively, Asian Americans had the shortest LOS and the lowest rates of complications due to ileus, respiratory, and renal complications (P < 0.001). There were no racial differences in 30-d mortality or readmission. On adjusted analyses, Asian American race was independently associated with less postoperative ileus (odds ratio 0.8, 95% confidence interval 0.66-0.98, P < 0.001) and decreased LOS by 13% and 4% compared with African American and Caucasian American patients, respectively (P < 0.001). CONCLUSIONS: Asian Americans undergoing surgery for colorectal cancer have shorter LOS and fewer POCs when compared with other racial/ethnic groups without differences in 30-d mortality or readmissions. The mechanism(s) underlying these disparities will require further study, but may be a result of patient, provider, and healthcare system differences. PMID- 28985855 TI - Safety of perioperative ketorolac administration in pediatric appendectomy. AB - BACKGROUND: Recent studies in adults undergoing gastrointestinal surgeries show an increased rate of complications with the use of ketorolac. This calls into question the safety of ketorolac in certain procedures. We sought to evaluate the impact of perioperative ketorolac administration on outcomes in pediatric appendectomy. METHODS: The Pediatric Health Information System database was queried for patients aged 5-17 y with a primary diagnosis of appendicitis and a primary procedure of appendectomy during the period 2010-2014. Patients with procedures suggesting incidental appendectomy, those records with data quality issues, deaths, and extracorporeal membrane oxygenation were excluded. Variables recorded included age, sex, race, ethnicity, discharge year, complex chronic conditions, geographic region, intensive care unit admission, mechanical ventilation, and whether appendicitis was coded as complicated. The exposure variable was ketorolac administration on the day of or day after operation. The primary outcomes of interest were any surgical complications during the initial encounter, postoperative length of stay (LOS), total cost for the initial visit, any readmission to ambulatory, observation, or inpatient status within 30 d, and readmission with a diagnosis of peritoneal abscess or other postoperative infection or with transabdominal drainage performed. RESULTS: A total of 78,926 patients were included in the analysis cohort. Mean age was 11.4 y (standard deviation 3.3 y), the majority were males (61%), White (70%), and non-Hispanic (65%). Few had a complex chronic condition (3%) or required mechanical ventilation (2%) or an intensive care unit admission (1%). Patients with complicated appendicitis comprised 28% of the cohort. Most (73%) received ketorolac on postoperative day 0-1; those with complicated appendicitis were more likely to receive ketorolac. In all, 2.6% of the cohort had a surgical complication during the index visit, 4.3% were readmitted within 30 d, and 2% had a postoperative infection or transabdominal drainage (1% in the uncomplicated group and 5% in the complicated group). Median postoperative LOS was 1 d and mean cost was $9811 +/- $9509. On bivariate analysis, ketorolac administration was associated with a decrease in same-visit surgical complications (P = 0.004) and cost ($459 decrease, P < 0.001) but was not associated with readmission, postoperative LOS, or postoperative infection. On multivariate analysis, ketorolac administration was associated with a significant decrease in any complication (adjusted odds ratio 0.89, 95% confidence interval 0.80-0.99) and cost (analysis of variance P < 0.001) but was not associated with readmission, postoperative LOS, or postoperative infection. CONCLUSIONS: Based on a large, contemporary data set from children's hospitals, ketorolac administration in the immediate postoperative period after appendectomy for appendicitis is common and was not associated with an increase in postoperative LOS, postoperative infection, or any-cause 30-d readmission. Ketorolac was, however, independently associated with a lower overall rate of postoperative complications and cost in this population. PMID- 28985856 TI - Papillary thyroid microcarcinoma: decision-making, extent of surgery, and outcomes. AB - BACKGROUND: The optimal extent of surgery for patients with papillary thyroid microcarcinoma (PTMC), tumors <=1 cm, is controversial because survival is excellent regardless of approach. The objective of this study was to investigate patient and surgeon decision-making about the extent of surgery for PTMC. MATERIALS AND METHODS: We conducted a retrospective review of thyroid cancer patients operated on at a single institution from 2008-2016. To examine decision making about the extent of surgery, we performed a discourse analysis on all available documentation looking for patient or surgeon reasons. RESULTS: Of the 853 thyroid cancer patients, 125 (14.7%) had a PTMC as their largest tumor. Overall, 27.2% of the PTMC patients underwent a thyroid lobectomy, whereas 72.8% had a total thyroidectomy (TT). Of those patients diagnosed with PTMC preoperatively (19/125), a significantly higher proportion underwent a TT (94.7% versus 68.9%, P = 0.02). In all cases, documentation indicated that these preoperatively diagnosed patients followed the surgeon's recommendation regarding the extent of surgery. Reasons surgeons cited for recommending a TT included patient and disease factors (34.6%), belief that TT was the standard treatment (21.7%), ease of follow-up (8.7%), and referring provider preference (4.3%). Of the 19 patients diagnosed preoperatively, four (21.1%) patients had a complication, one (5.3%) of which was permanent and potentially avoidable with less extensive surgery. CONCLUSIONS: These data suggest that surgeons drive decision-making about the extent of thyroidectomy in patients with preoperatively diagnosed PTMC. With recent guidelines recommending thyroid lobectomy, closer examination of decision-making is needed to ensure that patients make well informed, preference-based decisions. PMID- 28985857 TI - Cyclooxygenase 2 contributes to bradykinin-induced microvascular responses in peripheral arterioles after cardiopulmonary bypass. AB - BACKGROUND: Diabetic patients are associated with impaired peripheral microvascular function after cardiopulmonary bypass (CPB) and cardiac surgery. We hypothesized that upregulation of the inducible cyclooxygenase 2 (COX-2) contributes to altered microvascular reactivity of peripheral arterioles in diabetic patients undergoing CPB and cardiac surgery. METHODS: Skeletal muscle samples of nondiabetic (ND) patients and patients with diabetes mellitus (DM; n = 8 per group) undergoing cardiac surgery were harvested before and after CPB. The protein expression/localization of COX-2 was assayed by Western blotting and immunohistochemistry. Peripheral arterioles were dissected from the harvested skeletal muscle tissue samples, the isolated arterioles (80-180 MUm) were cannulated and pressurized, and changes in diameter were measured with video microscopy. In-vitro relaxation responses of precontracted arterioles were examined in the presence of the endothelium-dependent vasodilator bradykinin (10 10 to 10-6M) and in the presence or absence of the selective COX-2 inhibitor NS398 (10-5M). RESULTS: The post-CPB protein levels of the inducible COX-2 were significantly increased compared with pre-CPB values in both the ND and DM groups (P < 0.05), whereas, this increase was higher in DM than that of ND (P < 0.05). In the DM arterioles, not the ND vessels, bradykinin-induced relaxation response was inhibited in the presence of the specific COX-2 inhibitor NS398 at baseline (P < 0.05). After CPB, bradykinin-induced relaxation response of the ND and DM arterioles was inhibited in the presence of the specific COX-2 inhibitor NS398, but this effect was more pronounced in the diabetic patients (P < 0.05). CONCLUSIONS: Diabetes and CPB are associated with upregulation in COX-2 expression/activation in human peripheral microvasculature. This alteration may lead to altered peripheral microvascular reactivity in diabetic patients undergoing cardiac surgery. PMID- 28985858 TI - Increase in contralateral prophylactic mastectomy conversation online unrelated to decision-making. AB - BACKGROUND: The increased uptake of contralateral prophylactic mastectomy (CPM) among breast cancer patients remains poorly understood. We hypothesized that the increased rate of CPM is represented in conversations on an online breast cancer community and may contribute to patients choosing this operation. METHODS: We downloaded 328,763 posts and their dates of creation from an online breast cancer community from August 1, 2000, to May 22, 2016. We then performed a keyword search to identify posts which mentioned breast cancer surgeries: contralateral prophylactic mastectomy (n = 7095), mastectomy (n = 10,889), and lumpectomy (n = 9694). We graphed the percentage of CPM-related, lumpectomy-related, and mastectomy-related conversations over time. We also graphed the frequency of posts which mentioned multiple operations over time. Finally, we performed a qualitative study to identify factors influencing the observed trends. RESULTS: Surgically related posts (e.g., mentioning at least one operation) made up a small percentage (n = 27,678; 8.4%) of all posts on this community. The percentage of surgically related posts mentioning CPM was found to increase over time, whereas the percentage of surgically related posts mentioning mastectomy decreased over time. Among posts that mentioned more than one operation, mastectomy and lumpectomy were the procedures most commonly mentioned together, followed by mastectomy and CPM. There was no change over time in the frequency of posts that mentioned more than one operation. Our qualitative review found that most posts mentioning a single operation were unrelated to surgical decision making; rather the operation was mentioned only in the context of the patient's cancer history. Conversely, the most posts mentioning multiple operations centered around the patients' surgical decision-making process. CONCLUSIONS: CPM related conversation is increasing on this online breast cancer community, whereas mastectomy-related conversation is decreasing. These results appear to be primarily informed by patients reporting the types of operations they have undergone, and thus appear to correspond to the known increased uptake of CPM. PMID- 28985859 TI - In by helicopter out by cab: the financial cost of aeromedical overtriage of trauma patients. AB - BACKGROUND: Helicopter transport of injured patients is controversial and costly. This study aims to show that a complex trauma algorithm leads to significant aeromedical overtriage at substantial cost. Our secondary outcomes were to compare adjusted mortality and outcomes between air and ground transport and determine predictors of overtriage. MATERIALS AND METHODS: A 6-y retrospective analysis was conducted of all trauma activations at a Level I center. Patients were dichotomized by transportation method as well as trauma activation criteria. Overtriage was defined as those who were discharged from the emergency department, medically admitted without injuries, or admitted to observation status only. Overtriage and associated charges were calculated for each patient cohort, and multivariate regression models were created to derive adjusted mortality rates and predictors of overtriage. RESULTS: A total of 4218 patients were treated with 28% arriving by helicopter. Overtriage increased significantly from 51% to 77% with lower tier activation criteria (P < 0.001). Median charges for air-evacuated patients was $10,478 (versus $1008 ground). Eliminating overtriage of air patients would result in a cost savings of $1,316,036 annually. Adjusted mortality between air and ground transport was not significantly different (8.5% versus 10.9%, P = 0.548). Predictors of overtriage included decreasing age, Injury Severity Score, Head Abbreviated Injury Score, nonoperative treatment, and lower tier activation criteria. CONCLUSIONS: Significant overtriage (52%) and unnecessary air evacuation of minimally injured patients occurs at great financial cost. Revision of trauma activation protocols may result in more judicious air transport use and significant reductions in health care costs. PMID- 28985860 TI - A novel magnetic device for laparoscopic cholangiojejunostomy. AB - BACKGROUND: Laparoscopic cholangiojejunostomy (LCJ) with hand-sewn technique is technically difficult and requires a long time to master. The purpose of this study was to assess the feasibility of LCJ using a novel magnetic compression device (MCD) in dogs. METHODS: The concept of the purse-string technique of the circular stapler was used to design a novel MCD for LCJ. To test the feasibility of this MCD in a more clinically relevant situation, four dogs were subjected to bile duct ligation. When the diameter of their bile ducts reached 10 mm, LCJ using MCD was performed. The anastomotic time and expelling time of the magnets were assessed. RESULTS: In the clinically relevant model of bile duct obstruction in dogs, LCJ created with this MCD yielded patent anastomoses. The LCJ procedure using this novel MCD was simple, and the mean anastomotic time was 12.9 +/- 1.73 min. All animals recovered smoothly after the operation without complications. All magnets spontaneously passed through the rectum in 14.5 +/- 2.08 d after LCJ. CONCLUSIONS: LCJ in dogs using this novel MCD is feasible. PMID- 28985861 TI - Differences in rural and urban outcomes: a national inspection of emergency general surgery patients. AB - BACKGROUND: About 19% of the United States population lives in rural areas and is served by only 10% of the physician workforce. If this misdistribution represents a shortage of available surgeons, it is possible that outcomes for rural patients may suffer. The objective of this study was to explore differences in outcomes for emergency general surgery (EGS) conditions between rural and urban hospitals using a nationally representative sample. METHODS: Data from the 2007-2011 National Inpatient Sample were queried for adult patients (>=18 years) with a primary diagnosis consistent with an EGS condition, as defined by the American Association for the Surgery of Trauma. Urban and rural patients were matched on patient-level factors using coarsened exact matching. Differences in outcomes including mortality, morbidity, length of stay (LOS), and total cost of hospital care were assessed using multivariable regression models. Analogous counterfactual models were used to further examine hypothetical outcomes, assuming that all patients had been treated at urban centers. RESULTS: A total of 3,749,265 patients were admitted with an EGS condition during the study period. Of 3259 hospitals analyzed, 40.2% (n = 1310) were rural; they treated 14.6% of patients. Relative to urban centers, EGS patients treated at rural centers had higher odds of in-hospital mortality (odds ratio [OR]: 1.24; 95% confidence interval [CI]: 1.21-1.28) and lower odds of major complications (OR: 0.98; 95% CI: 0.96-0.99). Rural patients had 0.51 d (95% CI: 0.50-0.53) shorter LOS and $744 (95% CI: 712-774) higher cost of hospitalization compared to urban patients. In counterfactual models overall odds of death decreased by 0.05%, whereas the overall odds of complications increased by 0.02%. Overall difference in LOS and total costs were comparable with absolute differences of 0.08 d and $98, respectively. CONCLUSIONS: Despite the statistically significant difference in mortality and cost of care at rural versus urban hospitals, the magnitude of absolute differences is sufficiently small to indicate limited clinical importance. Large urban centers are designed to manage complex cases, but our results suggest that for cases appropriate to treat in rural hospitals, equivalent outcomes are found. These findings will inform future work on rural outcomes and provide impetus for regionalization of care for complex EGS presentations. PMID- 28985862 TI - Autophagy negatively regulates pro-osteogenic activity in human aortic valve interstitial cells. AB - BACKGROUND: Autophagy is a physiological process that plays an important role in maintaining cellular functions. When aortic valve interstitial cells (AVICs) are stimulated with inflammatory or mechanical stress, one response is elevated pro osteogenic activity. We hypothesized that autophagy is important in the prevention or regulation of this pro-osteogenic activity in AVICs. MATERIALS AND METHODS: AVICs were isolated. Autophagy activity was examined and its role in AVIC's pro-osteogenic activity was determined using chemical inhibitors and genetic techniques. The pro-osteogenic biomarker bone morphogenetic protein 2 (BMP-2) and alkaline phosphatase (ALP) were analyzed by immunoblotting and calcium deposition assay. RESULTS: Human AVICs from normal aortic valve donors displayed significantly higher autophagic activity than those from calcified aortic valve donors as indicated by lower protein levels of light chain 3-II. Suppression of autophagy by 3-methyladenine, bafilomycin, or knockdown of Atg7 gene induced the expression of BMP-2 and ALP, increased ALP activity, and calcium deposit formation in normal AVICs. Conversely, upregulation of autophagy with rapamycin or overexpression of Atg7 gene decreased the levels of BMP-2 and ALP in diseased AVICs. CONCLUSIONS: Our data showed that autophagy negatively regulates the pro-osteogenic activity in human AVICs, suggesting that upregulation of autophagy may prevent the progression of calcific aortic valve disease. PMID- 28985863 TI - Early declaration of death by neurologic criteria results in greater organ donor potential. AB - BACKGROUND: Aggressive management of patients prior to and after determination of death by neurologic criteria (DNC) is necessary to optimize organ recovery, transplantation, and increase the number of organs transplanted per donor (OTPD). The effects of time management are understudied but potentially pivotal component. The objective of this study was to analyze specific time points (time to DNC, time to procurement) and the time intervals between them to better characterize the optimal timeline of organ donation. METHODS: Using data over a 5 year time period (2011-2015) from the largest US OPO, all patients with catastrophic brain injury and donated transplantable organs were retrospectively reviewed. Active smokers were excluded. Maximum donor potential was seven organs (heart, lungs [2], kidneys [2], liver, and pancreas). Time from admission to declaration of DNC and donation was calculated. Mean time points stratified by specific organ procurement rates and overall OTPD were compared using unpaired t test. RESULTS: Of 1719 Declaration of Death by Neurologic Criteria organ donors, 381 were secondary to head trauma. Smokers and organs recovered but not transplanted were excluded leaving 297 patients. Males comprised 78.8%, the mean age was 36.0 (+/-16.8) years, and 87.6% were treated at a trauma center. Higher donor potential (>4 OTPD) was associated with shorter average times from admission to brain death; 66.6 versus 82.2 hours, P = 0.04. Lung donors were also associated with shorter average times from admission to brain death; 61.6 versus 83.6 hours, P = 0.004. The time interval from DNC to donation varied minimally among groups and did not affect donation rates. CONCLUSIONS: A shorter time interval between admission and declaration of DNC was associated with increased OTPD, especially lungs. Further research to identify what role timing plays in the management of the potential organ donor and how that relates to donor management goals is needed. PMID- 28985864 TI - Ultrasonography training and utilization in surgical critical care fellowships: a program director's survey. AB - BACKGROUND: Intensivist-performed ultrasound (IPUS) is an adjunctive tool used to assist in resuscitation and management of critically ill patients. It allows clinicians real-time information through noninvasive methods. We aimed to evaluate the types of IPUS performed and the methods surgical critical care (SCC) fellows are trained along with challenges in training. METHODS: One hundred SCC fellowship directors were successfully sent an email inviting them to participate in a short Web-based survey. We inquired about program characteristics including hospital type, fellowship size, faculty size and training, dedicated surgical critical care beds, and ultrasound equipment availability. The survey contained questions regarding the program directors' perception on importance on cost effectiveness of IPUS, types of IPUS examinations performed, fellows experience with IPUS, challenges to training, and presence and methods of quality assurance (QA) programs. RESULTS: A total of 38 (38.0%) program directors completed the survey. Using a 100-point Likert scale, the majority of the respondents indicated that IPUS is important to patient care in the SICU and is cost-effective (mean score 85.5 and 84.6, respectively). Most (34, 89.5%) utilize IPUS and conduct a mean of 5.1 different examination types with FAST being the most prevalent examination (33, 86.8%). Thirty-three (86.8%) programs include IPUS in their SCC training with varying amounts of time spent training. Of these programs, 19 (57.6%) have a specific curriculum. The most frequently used modalities for training fellows were informal bedside teaching (28, 84.8%), hands-on lectures (20, 60.6%) and formal lectures (19, 57.6%). The top three challenges program directors cited for IPUS education was time (23, 69.7%), followed by concerns for ongoing QA (19, 57.6%) and lack of faculty trained in IPUS (18, 53.9%). Only 20 (60.6%) programs review images as a part of QA/quality improvement. CONCLUSIONS: Utilization and training of IPUS is common in SCC fellowships. There is varied education type and training time devoted to IPUS which could lead to gaps in knowledge and care. Development of a standard curriculum for SCC fellowships could assist surgical intensivists in achieving a base of knowledge in IPUS to create a more homogenously trained workforce and standards of care. PMID- 28985865 TI - Personality traits within a pediatric surgery fellowship applicant pool. AB - BACKGROUND: The Big Five framework examines five factors that represent a description of human personality. These factors correlate with success measures and job satisfaction. The Big Five Inventory is a 44-item instrument designed to measure the Big Five framework. Our aim was to document the distribution of Big Five personality traits among Pediatric Surgery fellowship applicants, compare with community norms, surgical residents, between genders, and correlate to the fellowship match results. MATERIALS AND METHODS: Forty Pediatric Surgery fellowship applicants at a university hospital completed the Big Five Inventory during the interview process. It was analyzed and compared with general surgery residents' results and community norms. The data were compared regarding gender and match results. Continuous variables were compared by unpaired t-tests and Mann-Whitney tests. A P value <0.05 was considered significant. RESULTS: The 40 applicants were equally divided between male and female. When compared with general surgery residents and community norms, applicants of both genders scored higher on agreeableness (P < 0.01), conscientiousness (P < 0.01), and emotional stability (P < 0.01). Applicants scored higher on openness when compared with surgical residents (P < 0.01). Male applicants scored higher on emotional stability than females (P = 0.026). Matched applicants scored higher for conscientiousness than unmatched applicants (P = 0.016). CONCLUSIONS: Pediatric Surgery fellowship applicants expressed higher levels of desirable professional traits compared with general surgery residents and community norms. Male applicants demonstrated higher emotional stability than females. Conscientiousness was higher in matching applicants. This first reported experience with personality testing in Pediatric Surgery fellow selection demonstrated potential utility in applicant matching. PMID- 28985866 TI - A novel model of highly lethal uncontrolled torso hemorrhage in swine. AB - INTRODUCTION: A reproducible, lethal noncompressible torso hemorrhage model is important to civilian and military trauma research. Current large animal models balancing clinical applicability with standardization and internal validity. As such, large animal models of trauma vary widely in the surgical literature, limiting comparisons. Our aim was to create and validate a porcine model of uncontrolled hemorrhage that maximizes reproducibility and standardization. METHODS: Seven Yorkshire-cross swine were anesthetized, instrumented, and splenectomized. A simple liver tourniquet was applied before injury to prevent unregulated hemorrhage while creating a traumatic amputation of 30% of the liver. Release of the tourniquet and rapid abdominal closure following injury provided a standardized reference point for the onset and duration of uncontrolled hemorrhage. At the moment of death, the liver tourniquet was quickly reapplied to provide accurate quantification of intra-abdominal blood loss. Weight and volume of the resected and residual liver segments were measured. Hemodynamic parameters were recorded continuously throughout each experiment. RESULTS: This liver injury was rapidly and universally lethal (11.2 +/- 4.9 min). The volume of hemorrhage (35.8% +/- 6% of total blood volume) and severity of uncontrolled hemorrhage (100% of animals deteriorated to a sustained mean arterial pressure <35 mmHg for 5 min) were consistent across all animals. Use of the tourniquet effectively halted preprocedure and postprocedure blood loss allowing for accurate quantification of amount of hemorrhage over a defined period. In addition, the tourniquet facilitated the creation of a consistent liver resection weight (0.0043 +/- 0.0003 liver resection weight: body weight) and as a percentage of total liver resection weight (27% +/- 2.2%). CONCLUSIONS: This novel tourniquet assisted noncompressible torso hemorrhage model creates a standardized, reproducible, highly lethal, and clinically applicable injury in swine. Use of the tourniquet allowed for consistent liver injury and precise control over hemorrhage. Recorded blood loss was similar across all animals. Improving reproducibility and standardization has the potential to offer improvements in large animal translational models of hemorrhage. LEVEL OF EVIDENCE: Level I. PMID- 28985867 TI - Laparoscopic subtotal cholecystectomy compared to total cholecystectomy: a matched national analysis. AB - BACKGROUND: Laparoscopic subtotal cholecystectomy (LSC) is considered a safe alternative to laparoscopic cholecystectomy (LC) if biliary anatomy is obscured by inflammation. While case series studies have observed low morbidity rates with LSC, the impact of operative conversion on patient outcomes is poorly understood. METHODS: A national analysis of all patients who underwent LC or LSC from 2009 to 2013 was performed using the University HealthSystem Consortium database. A 1:1 propensity score match was used to compare procedural outcomes accounting for clinical and demographic factors. Matched samples had <10% standardized differences of each baseline covariate. RESULTS: A total of 131,082 LC and 487 LSC were performed during the study period. Compared with LC, patients undergoing LSC were more likely to be older (56 versus 48 years), male (54.2% versus 32.3%), and have higher severity of illness scores on admission (9.2% versus 3.5% extreme severity of illness; P < 0.001 each). LSC patients had a prolonged hospital length of stay (LOS, 4 versus 3 days), greater total direct cost ($9053 versus $6398), higher readmission rates (11.9% versus 7.0%), and higher mortality rates (0.82% versus 0.28%, P < 0.05 each). After matching, the difference in total direct cost persisted ($9053 versus $7,581, P < 0.001), but there were no differences in hospital LOS, readmission rates, or overall mortality. CONCLUSIONS: LSC is an important alternative to LC for the difficult gallbladder. Conversion to LSC is associated with increased patient morbidity and resource utilization leading to perceived poor outcomes, but this is due to patient factors at initial presentation. Health care providers should consider LSC if the patient may be at risk for iatrogenic injury to the biliary tract. PMID- 28985868 TI - Clinical and socioeconomic factors associated with negative pediatric appendicitis. AB - BACKGROUND: Misdiagnosing appendicitis may lead to unnecessary surgery. The study evaluates the risk factors for negative appendectomies, as well as the clinical and socioeconomic consequences of negative appendectomy across three states. MATERIALS AND METHODS: Data were obtained from the California, New York, and Florida State Inpatient Databases 2005-2011. Patients (<18 years) who underwent nonincidental appendectomies (n = 156,660) were evaluated with hierarchical and multivariate negative binomial regression analyses on outcomes including hospital cost, length of stay (LOS), and associated morbidity. RESULTS: From 2005 to 2011, there was a decrease in the rate of negative appendicitis and perforated appendicitis, whereas the rate of true acute nonperforated appendicitis increased. Whites, females, and privately insured patients were associated with higher negative appendicitis rates, whereas those at an increased risk for perforated appendicitis were African-Americans, males, and those with public or no insurance. Compared to patients with acute nonperforated appendicitis, those with negative appendicitis have significantly higher morbidity (2.5% versus 1.3%), longer LOS (3.4 versus 1.8 d), and greater hospital costs averaged over time ($6926 versus $6492 per patient). CONCLUSIONS: Despite a low incidence, negative appendicitis is associated with greater morbidity, longer LOS, and higher cost than acute nonperforated appendicitis. Certain subpopulations are at higher risk for undergoing surgery for negative appendicitis, whereas others are at greater risk for presenting with perforated appendicitis. Further research is needed to understand what drives such disparities and to inform efforts to improve quality of hospital care across all groups of patients. PMID- 28985869 TI - Surgical approach to gallbladder disease in rural Guatemala. AB - BACKGROUND: In this article, we report the current surgical approach to gallbladder disease at a major referral hospital in rural Guatemala. Complications in a cohort of patients undergoing open versus laparoscopic cholecystectomy were catalogued. METHODS: We reviewed cholecystectomies performed by surgeons at the Hospital Nacional de San Benito in El Peten, Guatemala, after the adoption of the laparoscopic approach. Laparoscopic cholecystectomies (LCs) between 2014 and 2015 (n = 42) were reviewed and matched by 58 randomly selected open cholecystectomies (OCs) during the same period. RESULTS: Patient demographics were similar in the LC and OC groups. Of the 63 patients who had elective surgery, 43 (68%) underwent OC. Conversion rate, hospital length of stay, and readmission rate were 4%, 4.8 days, and 5%, respectively. Complications were similar between groups. CONCLUSIONS: Despite the low number of LCs, their complications were not different from that of OCs. During the study period, a large number of cholecystectomies continued to be open, even in the elective setting. PMID- 28985870 TI - Polymeric micelles loaded with (1,2-diaminocyclohexane)platinum(II) against colorectal cancer. AB - BACKGROUND: We investigated the potential of nanomedicine in loading the oxaliplatin parent complex (1,2-diaminocyclohexane)platinum(II)-loaded polymeric micelles (DACHPt/m) against multiple liver metastases from colon cancer in a mouse model. MATERIALS AND METHODS: The efficacy of DACHPt/m or oxaliplatin (on days 14 and 21 after inoculation of tumor cells) was evaluated in a mouse model of liver metastasis for murine colon adenocarcinoma C26 cells. In vivo antitumor effects were evaluated by recording the number of liver metastases and weights of metastatic livers after treatment (day 28). The accumulation of drugs in tumors and liver parenchyma was analyzed using ion coupled plasma-mass spectrometry 24 h after administration of DACHPt/m or oxaliplatin (n = 5). We assessed renal and hepatic toxicities through changes in creatinine, aspartate transaminase, and alanine transaminase on the last day of the antitumor activity experiment. RESULTS: Mice receiving DACHPt/m had significantly fewer metastatic nodules (P = 0.038) and lower liver weights (P = 0.038) than those receiving oxaliplatin. The accumulation of DACHPt/m in the metastatic liver was significantly higher than that of oxaliplatin, whereas the distribution of micelles in healthy liver tissues was limited. Mice treated with DACHPt/m also showed significantly lower serum creatinine levels than those treated with oxaliplatin (P = 0.007), whereas serum aspartate transaminase and alanine transaminase levels for both drugs were not different. CONCLUSIONS: High levels of DACHPt/m accumulate in metastatic livers, producing a strong antitumor effect without severe adverse effects. DACHPt/m is a safe approach for managing liver metastasis from colorectal cancer. PMID- 28985871 TI - Ex vivo treatment with inhaled N-acetylcysteine in porcine lung transplantation. AB - BACKGROUND: We have shown the beneficial effects of N-acetylcysteine (NAC) on posttransplant lung function, when both donor and recipient were pretreated intravenously. However, systemic treatment of multiorgan donors may not be clinically relevant. Thus, we hypothesized that ex vivo treatment of donors with nebulized NAC would be adequate to prevent from ischemia-reperfusion injury after lung transplantation. METHODS: Lungs were retrieved from domestic pigs and stored at 4 degrees C for 24 h followed by 2 h of ex vivo lung perfusion (EVLP) to administer 50 mg/kg of NAC via nebulization in the NAC group (n = 6). The control group received nebulized saline (n = 5). Left lungs were transplanted and isolated at 1 h of reperfusion by occluding the right main bronchus and pulmonary artery, followed by 5 h of observation. Physiological data during EVLP and after reperfusion were recorded. Inflammatory response, markers of oxidative stress, and microscopic lung injury were analyzed. RESULTS: There was a trend toward better oxygenation throughout reperfusion period in the treatment group, which was accompanied by inhibited inflammatory response related to reduction in myeloperoxidase activity during EVLP and nuclear factor-kappaB activation at the end of reperfusion. CONCLUSIONS: Ex vivo treatment of donor lungs with inhaled NAC reduced inflammatory response via its antioxidant activity in experimental porcine lung transplantation. PMID- 28985872 TI - Are nonemergent cardiac operations performed during off-time associated with worse outcome? AB - BACKGROUND: With the implementation of value-based health care, it is of increasing interest to understand whether performing elective surgeries during off-time impacts surgical outcomes. The objective of this study was to evaluate the impact of start times on nonemergent cardiac operations. METHODS: The institutional Society of Thoracic Surgeons was used to identify all adult nonemergent cardiac operations performed between January 2008 and December 2015 at our institution. "Off-time" is defined as either operation "late starts," that is, an incision time after 3 PM and before 7 AM, or procedures occurring during the weekends. Univariate and multivariate logistic regression analyses were performed to examine its impact on in-hospital mortality and major adverse events. Available cost data were directly obtained from the departmental BIOME database. RESULTS: Of the 3406 cardiac operations included in the study, 2933 (86.1%) were normal-start and 473 (13.9%) were off-time-start operations. After adjusting for patient and operative characteristics, late operating room start times were not associated with increased in-hospital mortality (P = 0.28, confidence interval [CI] 95% = 0.99-1.03), readmissions (P = 0.21, CI 95% = 0.99 1.07), or major adverse events (P = 0.07, CI 95% = 1.00-1.12). In addition, there was no significant impact on total hospital cost (9.0% increase, P = 0.07). CONCLUSIONS: These findings suggest that late operating room start times are not associated with increased mortality or other complications in a tertiary-care academic medical center. Our findings should be considered during operative scheduling to optimize resource distribution and patient care strategies. PMID- 28985873 TI - Intestinal alkaline phosphatase deficiency leads to dysbiosis and bacterial translocation in the newborn intestine. AB - BACKGROUND: Intestinal alkaline phosphatase (IAP) has been shown to help maintain intestinal homeostasis. Decreased expression of IAP has been linked with pediatric intestinal diseases associated with bacterial overgrowth and subsequent inflammation. We hypothesize that the absence of IAP leads to dysbiosis, with increased inflammation and permeability of the newborn intestine. METHODS: Sprague-Dawley heterozygote IAP cross-matches were bred. Pups were dam fed ad lib and euthanized at weaning. The microbiotas of terminal ileum (TI) and colon was determined by quantitative real-time polymerase chain reaction (qRT-PCR) of subphylum-specific bacterial 16S ribosomal RNA. RT-PCR was performed on TI for inflammatory cytokines. Intestinal permeability was quantified by fluorescein isothiocyanate-dextran permeability and bacterial translocation by qRT-PCR for bacterial 16S ribosomal RNA in mesenteric lymph nodes. Statistical analysis was done by chi-square analysis. RESULTS: All three genotypes had similar concentrations of bacteria in the TI and colon. However, IAP knockout (IAP-KO) had significantly decreased diversity of bacterial species in their colonic stool compared with heterozygous and wild-type (WT). IAP-KO pups had a nonstatistically significant 3.9-fold increased inducible nitric oxide synthase messenger RNA expression compared with WT (IAP-KO, 3.92 +/- 1.36; WT, 1.0 +/- 0.27; P = 0.03). IAP-KO also had significantly increased bacterial translocation to mesenteric lymph nodes occurred in IAP-KO (IAP-KO, 7625 RFU/g +/- 3469; WT, 4957 RFU/g +/- 1552; P = 0.04). Furthermore, IAP-KO had increased permeability (IAP-KO, 0.297 mg/mL +/- 0.2; WT, 0.189 mg/mL +/- 0.15 P = 0.07), but was not statistically significant. CONCLUSIONS: Deficiency of IAP in the newborn intestine is associated with dysbiosis and increased inflammation, permeability, and bacterial translocation. PMID- 28985874 TI - Bioscaffold-mediated mucosal remodeling following short-segment colonic mucosal resection. AB - Precancerous or cancerous lesions of the gastrointestinal tract often require surgical resection via endomucosal resection. Although excision of the colonic mucosa is an effective cancer treatment, removal of large lesions is associated with high morbidity and complications including bleeding, perforation, fistula formation, and/or stricture, contributing to high clinical and economic costs and negatively impacting patient quality of life. The present study investigates the use of a biologic scaffold derived from extracellular matrix (ECM) to promote restoration of the colonic mucosa following short segment mucosal resection. Six healthy dogs were assigned to ECM-treated (tubular ECM scaffold) and mucosectomy only control groups following transanal full circumferential mucosal resection (4 cm in length). The temporal remodeling response was monitored using colonoscopy and biopsy collection. Animals were sacrificed at 6 and 10 wk, and explants were stained with hematoxylin and eosin (H&E), Alcian blue, and proliferating cell nuclear antigen (PCNA) to determine the temporal remodeling response. Both control animals developed stricture and bowel obstruction with no signs of neomucosal coverage after resection. ECM-treated animals showed an early mononuclear cell infiltrate (2 weeks post-surgery) which progressed to columnar epithelium and complex crypt structures nearly indistinguishable from normal colonic architecture by 6 weeks after surgery. ECM scaffold treatment restored colonic mucosa with appropriately located PCNA+ cells and goblet cells. The study shows that ECM scaffolds may represent a viable clinical option to prevent complications associated with endomucosal resection of cancerous lesions in the colon. PMID- 28985875 TI - Safety considerations in learning new procedures: a survey of surgeons. AB - BACKGROUND: There exists a tension between surgical innovation and safety. The learning curve associated with the introduction of new procedures/technologies has been associated with preventable patient harm. Surgeon's perceptions regarding the safety of methods for learning new procedures/technologies are largely uncharacterized. MATERIALS AND METHODS: A survey was designed to evaluate surgeons' perceptions related to learning new procedures/technologies. This included clinical vignettes across two domains: (1) experience with an operation (e.g., colectomy) and (2) experience with a technology (e.g., laparoscopy). This study also focuses on a surgeon's perceptions of existing credentialing/privileging requirements. Participants were faculty surgeons (n = 150) at two large Midwestern academic health centers. RESULTS: Survey response rate was 77% (116/150). 69% of respondents believed the processes of credentialing/privileging is "far too relaxed" or "too relaxed" for ensuring patient safety. Surgeons most commonly indicated a mini-fellowship is required to learn a new laparoscopic procedure. However, that requirement differed based on a surgeon's prior experience with laparoscopy. For example, to learn laparoscopic colectomy, 35% of respondents felt a surgeon with limited laparoscopic experience should complete a mini-fellowship, whereas 3% felt this was necessary if the surgeon had extensive laparoscopic experience. In the latter scenario, most respondents felt a surgeon should scrub in cases performed by an expert (38%) or perform cases under a proctor's supervision (33%) when learning laparoscopic colectomy. CONCLUSIONS: Many surgeons believe existing hospital credentialing/privileging practices may be too relaxed. Moreover, surgeons believe the "one-size-fits-all" approach for training practicing surgeons may not protect patients from unsafe introduction of new procedures/technologies. PMID- 28985876 TI - The readability of psychosocial wellness patient resources: improving surgical outcomes. AB - BACKGROUND: Patient education is increasingly accessed with online resources and is essential for patient satisfaction and clinical outcomes. The average American adult reads at a seventh grade level, and the National Institute of Health (NIH) and the American Medical Association (AMA) recommend that information be written at a sixth-grade reading level. Health literacy plays an important role in the disease course and outcomes of all patients, including those with depression and likely other psychiatric disorders, although this is an area in need of further study. The purpose of this study was to collect and analyze written, online mental health resources on the Veterans Health Administration (VA) website, and other websites, using readability assessment instruments. METHODS: An internet search was performed to identify written patient education information regarding mental health from the VA (the VA Mental Health Website) and top-rated psychiatric hospitals. Seven mental health topics were included in the analysis: generalized anxiety disorder, bipolar, major depressive disorder, posttraumatic stress disorder, schizophrenia, substance abuse, and suicide. Readability analyses were performed using the Gunning Fog Index, the Flesch-Kincaid Grade Level, the Coleman-Liau Index, the SMOG Readability Formula, and the Automated Readability Index. These scores were then combined into a Readability Consensus score. A two-tailed t-test was used to compare the mean values, and statistical significance was set at P < 0.05. RESULTS: Twelve of the best hospitals for psychiatry 2016-2017 were identified. Nine had educational material. Six of the nine cited the same resource, The StayWell Company, LLC (StayWell Company, LLC; Yardley, PA), for at least one of the mental health topics analyzed. The VA mental health website (http://www.mentalhealth.va.gov) had a significantly higher readability consensus than six of the top psychiatric hospitals (P < 0.05, P = 0.0067, P = 0.019, P = 0.041, P = 0.0093, P = 0.0054, and P = 0.0093). The overall average readability consensus for mental health information on all websites analyzed was 9.52. CONCLUSIONS: Online resources for mental health disorders are more complex than recommended by the NIH and AMA. Efforts to improve readability of mental health and psychosocial wellness resources could benefit patient understanding and outcomes, especially in patients with lower literacy. Surgical outcomes are correlated with patient mental health and psychosocial wellness and thus can be improved with more appropriate levels of readability of psychosocial wellness resources. PMID- 28985877 TI - Intra-graft injection of tacrolimus promotes survival of vascularized composite allotransplantation. AB - BACKGROUND: Immunosuppressive therapies derived from solid organ transplantation are effective in promoting survival of vascularized composite allotransplantation (VCA), but they cause serious side effects that are difficult to justify for this non-life-saving procedure. Unlike solid organ transplantation, hand and face transplants offer the possibility of site-specific immunosuppression for reducing systemic exposure while increasing intra-graft concentrations of the drug. Therefore, in this study, we tested whether a single intra-graft injection tacrolimus could promote VCA survival. METHODS: Brown Norway-to-Lewis hind limb transplantations were performed, and animals were left untreated (group I), treated with a daily injection of 1-mg/kg tacrolimus for 21 days (group 2) or injected with 7-mg tacrolimus directly into the transplanted limb on day 1 (group III). Graft rejection was monitored, and animals were sacrificed at grade 3 rejection or 200 days after transplantation. RESULTS: Intra-graft injection of tacrolimus significantly prolonged allograft survival as compared to untreated animals or animals treated with systemic tacrolimus. Half of the intra-graft treated rats rejected their graft on average at day 70.5. Interestingly, the other half remained rejection-free for more than 200 days without signs of kidney or liver toxicity. In these animals, tacrolimus was detected in the VCA skin but not in the blood until day 200. Long-term survival was not linked to induction of donor-specific tolerance but to a higher level of lymphocyte chimerism. CONCLUSIONS: Intra-graft delivery of tacrolimus may promote VCA survival by increasing tissue drug availability and promoting the establishment of transient chimerism and thus long-term graft acceptance. PMID- 28985878 TI - Effect of surgery-induced acute muscle wasting on postoperative outcomes and quality of life. AB - BACKGROUND: Gastrectomy results in a significant loss of body composition in the long term, but the acute skeletal muscle wasting after gastrectomy has been rarely investigated. Moreover, the association between postoperative muscle wasting and quality of life (QOL) has never been reported. In the present study, we aimed to investigate the risk factors for acute muscle wasting after gastric cancer surgery and its effect on QOL and short-term postoperative outcomes. METHODS: We conducted a prospective study of patients who underwent curative gastrectomy for gastric cancer between June 2015 and December 2015. Skeletal muscle mass was measured by computed tomography within 1 month before and 1 week after surgery. QOL was assessed 1, 3, and 6 months postoperatively. Univariate and multivariate analyses were performed to identify the risk factors for clinically relevant muscle wasting (muscle wasting >=10%). RESULTS: A total of 110 patients were included, in which 35 patients had muscle wasting >=10% within 1 week after surgery. Age >=65 years and diabetes were independent risk factors for muscle wasting >=10%. Patients with muscle wasting >=10% had a poorer QOL in terms of fatigue and physical functioning at 1 and 3 months postoperatively, as well as a higher incidence of postoperative complications, a higher incidence of handgrip strength reduction >=10%, longer hospital stays, and higher costs. CONCLUSIONS: Age >=65 years and diabetes were independently associated with clinically relevant muscle wasting within 1 week after gastric cancer surgery. Clinically relevant muscle wasting was associated with a poorer QOL and short term outcomes after surgery. PMID- 28985879 TI - Resource utilization associated with cervical hematoma after thyroid and parathyroid surgery. AB - BACKGROUND: Postoperative cervical hematoma (PCH) after thyroid and parathyroid surgery is a well-known complication. This study used data from the Nationwide Inpatient Sample to identify risk factors, estimate mortality, length of stay (LOS), and total costs attributable to PCH in patients undergoing procedures for thyroid and parathyroid diseases. METHODS: Patients aged >18 y who underwent thyroid or parathyroid surgery between 2001 and 2011 were identified and stratified by the occurrence of PCH. Univariate analyses of patient demographics, clinical and hospital characteristics were performed. Multivariable logistic regression was used to determine risk factors for hematoma formation. LOS and costs were fit to linear regression models to determine the effect of PCH after adjusting for patient and hospital characteristics. RESULTS: Of patients who underwent thyroid or parathyroid surgery, 619 patients (0.8%) had a PCH. Predisposing factors included nonelective admission (emergent: OR = 2.01, P < 0.0001; urgent: OR = 1.47, P = 0.003), diagnosis of Graves' disease (OR = 1.90, P < 0.0001), or other benign pathology (OR = 1.43, P = 0.011) and having >=2 comorbidities (2-3 comorbidities, OR = 1.24; P = 0.036 and >= 4 comorbidities, OR = 2.28; P < 0.0001). After adjusting for those characteristics, the total excess LOS and costs attributable to PCH were 2.1 d (P < 0.0001) and $7316 (P < 0.0001), respectively. In addition, after risk adjustment, odds of mortality more than tripled (P < 0.0001) in the setting of PCH. CONCLUSIONS: Because risk for PCH is largely driven by preoperative patient risk factors, five clinicians have an opportunity to stratify patients accordingly and thereby minimize the resource utilization and health care spending among those with lowest risk. PMID- 28985880 TI - Trends in parastomal hernia repair in the United States: a 14-y review. AB - BACKGROUND: Parastomal hernia is the most common complication after stoma creation. Parastomal hernias can create significant morbidity, including patient discomfort, small bowel obstruction, and need for emergency surgery. We examined national trends in parastomal hernia repair (PHR) including annual frequency of procedure, patient characteristics, and same-admission complications. MATERIALS AND METHODS: The 1998-2011 Nationwide Inpatient Sample was used to identify patients who underwent a PHR (International Classification of Disease, Ninth Edition, Procedure Code [ICD-9 PR] 46.42). PHRs were classified as PHR with concurrent resiting (ICD-9 PR 46.43), PHR with concurrent ostomy reversal (ICD-9 PR 46.52 or 46.51), or primary PHR. Patient characteristics were collected. Complications, length of stay, cost and inpatient mortality were identified. RESULTS: The estimated number of annual PHRs increased from 4150 to 7623 (P <= 0.01) for a total of 73,393 repairs. Thirty percent underwent a concurrent stoma reversal and 10% underwent a resiting. There was an upward trend in number of patients with >=3 Elixhauser comorbidities (17%-44%, P < 0.01). Length of stay remained steady, with a median of 6.3 d and in-hospital annual mortality ranged from 1.8% to 3.9%. Mortality and emergency admission status were highest for patients who underwent primary PHR. CONCLUSIONS: The incidence of PHR nationwide is increasing and more than half of patients undergo primary repair. Although the surgical focus has moved toward prevention, parastomal hernia is a persistent complication of stoma creation. Further exploration is warranted to determine contributing factors to the observed increase in PHR and changes in surgical technique. PMID- 28985881 TI - Discontinuous insurance coverage predicts prolonged hospital stay after pediatric adenotonsillectomy. AB - BACKGROUND: Changes in health insurance coverage have been implicated in limiting access to care and increasing morbidity risk. The consequences of insurance discontinuity for surgical outcomes are unclear. In this study, we explored whether recent insurance discontinuity was associated with prolonged inpatient hospitalization after adenotonsillectomy in children. MATERIALS AND METHODS: We retrospectively evaluated single-center data on children aged 2-18 y undergoing adenotonsillectomy with overnight stay in 2009-2014. Insurance coverage at surgery and over the preceding year was categorized as (1) continuous private, (2) continuous Medicaid, or (3) discontinuous (changes or gaps in coverage). The association between insurance discontinuity and prolonged hospitalization (>=2 d) was evaluated using multivariable logistic regression. RESULTS: The study included 1013 girls and 983 boys (aged 4.5 +/- 2.9 y), of whom 205 (10%) required prolonged hospitalization. Insurance was continuous private for 749 patients (38%), continuous Medicaid for 1121 patients (56%), and discontinuous for 126 patients (6%). Prolonged stay was most common with discontinuous insurance (23/126, 18%), followed by continuous Medicaid (117/1,121, 10%), and continuous private insurance (65/749, 9%; P = 0.004). In multivariable analysis, discontinuous insurance remained associated with prolonged hospital stay, compared with continuous private insurance (odds ratio = 1.88; 95% confidence interval: 1.06-3.33; P = 0.031), and compared with continuous Medicaid (odds ratio = 1.86; 95% confidence interval: 1.09-3.19; P = 0.023). CONCLUSIONS: This study demonstrates greater odds of prolonged hospitalization after adenotonsillectomy among children with recent gaps or changes in insurance coverage and illustrates the feasibility of studying influences of health insurance change on surgical outcomes using existing data in hospital electronic records. PMID- 28985882 TI - Economic evaluations of comprehensive geriatric assessment in surgical patients: a systematic review. AB - BACKGROUND: Seniors presenting with surgical disease face increased risk of postoperative morbidity and mortality and have increased treatment costs. Comprehensive Geriatric Assessment (CGA) is proposed to reduce morbidity, mortality, and the cost after surgery. METHODS: A systematic review of CGA in emergency surgical patients was conducted. The primary outcome was cost effectiveness; secondary outcomes were length of stay, return of function, and mortality. Inclusion and exclusion criteria were predefined. Systematic searches of MEDLINE, Embase, Cochrane, and National Health Service Economic Evaluation Database were performed. Text screening, bias assessment, and data extraction were performed by two authors. RESULTS: There were 560 articles identified; abstract review excluded 499 articles and full-text review excluded 53 articles. Eight studies were included; one nonorthopedic trauma and seven orthopedic trauma studies. Bias assessment revealed moderate to high risk of bias for all studies. Economic evaluation assessment identified two high-quality studies and six moderate or low quality studies. Pooled analysis from four studies assessed loss of function; loss of function decreased in the experimental arm (odds ratio 0.92, 95% confidence interval [CI]: 0.88-0.97). Pooled results for length of stay from five studies found a significant decrease (mean difference: -1.17, 95% CI: -1.63 to -0.71) after excluding the nonorthopedic trauma study. Pooled mortality was significantly decreased in seven studies (risk ratio: 0.78, 95% CI: 0.67-0.90). All studies decreased cost and improved health outcomes in a cost-effective manner. CONCLUSIONS: CGA improved return of function and mortality with reduced cost or improved utility. Our review suggests that CGA is economically dominant and the most cost-effective care model for orthogeriatric patients. Further research should examine other surgical fields. PMID- 28985883 TI - Outpatient follow-up does not prevent emergency department utilization by trauma patients. AB - BACKGROUND: Although most trauma centers have a regularly scheduled trauma clinic, research demonstrates that trauma patients do not consistently attend follow-up appointments and often use the emergency department (ED) for outpatient care. METHODS: A retrospective review of outpatient follow-up of adult patients admitted to the trauma service (January 2014-December 2014) at an urban level I trauma center was conducted (n = 2134). RESULTS: A total of 219 patients (10%) were evaluated in trauma clinic after discharge from the hospital. Twenty-one percent of patients seen in trauma clinic visited the ED within 30 d compared with 12% of those not seen in clinic (P < 0.001). A total of 104 patients were readmitted within 30 d of discharge; no difference existed in the rate of hospital readmission between patients seen in clinic and those not seen in clinic (P = 0.25). Stepwise logistic regression showed that clinic follow-up was not a significant predictor of decreased ED utilization (adjusted odds ratio [OR] 1.16 [95% confidence interval 0.78-1.72], P = 0.461) and also showed that while ED use was a significant predictor of readmission (adjusted OR 216 [93-500], P < 0.001), clinic visits were not (adjusted OR 0.74 [0.33-1.69], P = 0.48). CONCLUSIONS: Outpatient follow-up in the trauma clinic does not decrease ED utilization or hospital readmissions indicating that interventions aimed at improving access to a conventional outpatient clinic will not impact ED utilization rates. Further study is necessary to determine the best system for providing clinically appropriate and cost-effective outpatient follow-up for trauma patients. PMID- 28985884 TI - Gender differences in academic surgery, work-life balance, and satisfaction. AB - BACKGROUND: An increasing number of women are pursuing a career in surgery. Concurrently, the percentage of surgeons in dual-profession partnerships is increasing. We sought to evaluate the gender differences in professional advancement, work-life balance, and satisfaction at a large academic center. MATERIALS AND METHODS: All surgical trainees and faculty at a single academic medical center were surveyed. Collected variables included gender, academic rank, marital status, family size, division of household responsibilities, and career satisfaction. Student t-test, Fisher's exact test, and chi-square test were used to compare results. RESULTS: There were 127 faculty and 116 trainee respondents (>80% response rate). Respondents were mostly male (77% of faculty, 58% of trainees). Women were more likely than men to be married to a professional (90% versus 37%, for faculty; 82% versus 41% for trainees, P < 0.001 for both) who was working full time (P < 0.001) and were less likely to be on tenure track (P = 0.002). Women faculty were more likely to be primarily responsible for childcare planning (P < 0.001), meal planning (P < 0.001), grocery shopping (P < 0.001), and vacation planning (P = 0.003). Gender-neutral responsibilities included financial planning (P = 0.04) and monthly bill payment (P = 0.03). Gender differences in division of household responsibilities were similar in surgical trainees except for childcare planning, which was a shared responsibility. CONCLUSIONS: Women surgeons are more likely to be partnered with a full-time working spouse and to be primarily responsible for managing their households. Additional consideration for improvement in recruitment and retention strategies for surgeons might address barriers to equalizing these gender disparities. PMID- 28985885 TI - Head and neck ultrasound: technical advances, novel applications and the role of elastography. AB - High-resolution ultrasound (US) provides superb anatomical detail in the superficial anatomy of the neck and has become the first-line imaging investigation for neck lumps and a crucial component of clinical pathways. In this article, a wide range of advances in neck US are described with a focus on the emerging role of ultrasound elastography. Selected examples of clinical utility are presented across a spectrum of scenarios with discussion of newer applications, service delivery, and training issues. The changing role of the neck ultrasound practitioner and the future of the technique in the head and neck are considered. PMID- 28985886 TI - Debatable issues in automated ECG reporting. AB - Although automated ECG analysis has been available for many years, there are some aspects which require to be re-assessed with respect to their value while newer techniques which are worthy of review are beginning to find their way into routine use. At the annual International Society of Computerized Electrocardiology conference held in April 2017, four areas in particular were debated. These were a) automated 12 lead resting ECG analysis; b) real time out of hospital ECG monitoring; c) ECG imaging; and d) single channel ECG rhythm interpretation. One speaker presented the positive aspects of each technique and another outlined the more negative aspects. Debate ensued. There were many positives set out for each technique but equally, more negative features were not in short supply, particularly for out of hospital ECG monitoring. PMID- 28985887 TI - The Dressler - de Winter sign of acute proximal LAD occlusion. PMID- 28985888 TI - Speech sound disorders or differences: Insights from bilingual children speaking two Chinese languages. AB - The study investigated how Putonghua-Cantonese bilingual children differ from monolinguals in their acquisition of speech sound and phonological patterns. Fifty-four typically developing Putonghua-Cantonese bilingual children aged 3;6 6;0 were recruited from nurseries in the North District of Hong Kong. The Hong Kong Cantonese Articulation Test (Cheung et al., 2006) and a Putonghua picture naming task (Zhu & Dodd, 2000) were used to elicit single-word samples of both languages. Acquisition of speech sound and phonological patterns exhibited by >=20% of the children in an age group were compared to the normative data on children who were Cantonese native or Putonghua monolingual speakers. The bilingual children demonstrated smaller sound inventory in both languages and more delayed and atypical phonological processes. The atypical patterns could be explained by phonological interference between Putonghua and Cantonese. The findings serve as a preliminary reference for clinicians in differentiating language difference from true speech sound disorders in Putonghua-Cantonese bilingual children in Hong Kong. PMID- 28985889 TI - Discussion of: "Radioactive seed localization for breast conservation surgery: Low positive margin rate with no learning curve". PMID- 28985890 TI - Discussion of: "Perioperative complications increase the risk of venous thromboembolism following bariatric surgery". PMID- 28985891 TI - A three-step method for modular lymphadenectomy in gastric cancer surgery: The ability to retrieve sufficient lymph nodes and improve survival. AB - BACKGROUND: Systematic lymphadenectomy for the resection of sufficient lymph nodes is the most important part of curative resection in gastric cancer surgery. Here, we explore the outcomes of the three-step method for modular lymphadenectomy (TSMML) and determine its safety and efficacy, compared with the conventional method for lymphadenectomy (CML). METHODS: From 2008 to 2011, 270 patients with gastric cancer were divided into 2 subgroups: the TSMML group and the CML group. RESULTS: Patients in the TSMML group had a significantly higher median number of retrieved lymph nodes (rLNs), lower median metastatic lymph node ratios (MLRs), and superior 5-year relapse-free survival (RFS) than the CML group. Moreover, the use of the TSMML procedure was an independent protective factor for RFS. No significant intergroup differences were found in morbidity or mortality in these two groups. CONCLUSION: The TSMML procedure is safe and effective and is easy to learn. PMID- 28985892 TI - Laparoscopic donor nephrectomy: A single institution minimally invasive general surgeon experience 1999-2013. AB - BACKGROUND: Laparoscopic donor nephrectomy (LDN) is the standard of care for donor nephrectomies. No large series reports have been published detailing the LDN experience of minimally invasive general surgeons. METHODS: A retrospective review of 526 LDNs performed by MIS general surgeons at Baylor University Medical Center between 1999 and 2013. Complications were graded on the Clavien scale. The learning curve was determined by procedure time. RESULTS: The complication rate was 3.0%. Female donors had shorter operative time than males (141 vs 162 min). Warm ischemia time was shorter with female donors and left kidney procurement. There were six recipient graft losses within 30 days of the transplant. Operative time plateaued after 27 cases. CONCLUSION: MIS general surgeons using a standardized technique can learn and perform a new, unfamiliar procedure with excellent results. Women are easier to perform organ harvest than men. Organ harvest from obese patients can be safely performed. PMID- 28985893 TI - Metabolic responses induced by compression of chondrocytes in variable-stiffness microenvironments. AB - Cells sense and respond to mechanical loads in a process called mechanotransduction. These processes are disrupted in the chondrocytes of cartilage during joint disease. A key driver of cellular mechanotransduction is the stiffness of the surrounding matrix. Many cells are surrounded by extracellular matrix that allows for tissue mechanical function. Although prior studies demonstrate that extracellular stiffness is important in cell differentiation, morphology and phenotype, it remains largely unknown how a cell's biological response to cyclical loading varies with changes in surrounding substrate stiffness. Understanding these processes is important for understanding cells that are cyclically loaded during daily in vivo activities (e.g. chondrocytes and walking). This study uses high-performance liquid chromatography - mass spectrometry to identify metabolomic changes in primary chondrocytes under cyclical compression for 0-30minutes in low- and high-stiffness environments. Metabolomic analysis reveals metabolites and pathways that are sensitive to substrate stiffness, duration of cyclical compression, and a combination of both suggesting changes in extracellular stiffness in vivo alter mechanosensitive signaling. Our results further suggest that cyclical loading minimizes matrix deterioration and increases matrix production in chondrocytes. This study shows the importance of modeling in vivo stiffness with in vitro models to understand cellular mechanotransduction. PMID- 28985894 TI - In vivo fascicle length measurements via B-mode ultrasound imaging with single vs dual transducer arrangements. AB - Ultrasonography is a useful technique to study muscle contractions in vivo, however larger muscles like vastus lateralis may be difficult to visualise with smaller, commonly used transducers. Fascicle length is often estimated using linear trigonometry to extrapolate fascicle length to regions where the fascicle is not visible. However, this approach has not been compared to measurements made with a larger field of view for dynamic muscle contractions. Here we compared two different single-transducer extrapolation methods to measure VL muscle fascicle length to a direct measurement made using two synchronised, in-series transducers. The first method used pennation angle and muscle thickness to extrapolate fascicle length outside the image (extrapolate method). The second method determined fascicle length based on the extrapolated intercept between a fascicle and the aponeurosis (intercept method). Nine participants performed maximal effort, isometric, knee extension contractions on a dynamometer at 10 degrees increments from 50 to 100 degrees of knee flexion. Fascicle length and torque were simultaneously recorded for offline analysis. The dual transducer method showed similar patterns of fascicle length change (overall mean coefficient of multiple correlation was 0.76 and 0.71 compared to extrapolate and intercept methods respectively), but reached different absolute lengths during the contractions. This had the effect of producing force-length curves of the same shape, but each curve was shifted in terms of absolute length. We concluded that dual transducers are beneficial for studies that examine absolute fascicle lengths, whereas either of the single transducer methods may produce similar results for normalised length changes, and repeated measures experimental designs. PMID- 28985895 TI - When attended and conscious perception deactivates fronto-parietal regions. AB - The finding of increased fronto-parietal activity during conscious and attended perception forms a key basis for theories of consciousness and attention. However, this finding comes largely from studies that required explicit detection of events in a way that made detection the goal of the ongoing task. This is an important confound because goal completion itself elicits fronto-parietal activity. In everyday life attended and conscious perception is instrumental in achieving our goals but rarely a goal in itself. Here we examined whether conscious perception that was instrumental to participants' current goals, but not a goal in itself, elicited increased fronto-parietal activity. In Experiments 1 and 2 participants attended to a stream of letters (1 per second) to detect occasional targets in their midst. We found that consciousness of, and attention to, these highly visible non-targets events deactivated fronto-parietal regions. In Experiment 3 participants heard a loud auditory cue that had to be retained in memory for up to 9 sec before being used to select the correct rule for completing the goal. No increased fronto-parietal activity was observed even for such salient, attended and remembered event. In contrast, robust fronto-parietal activation was observed across all the experiments for goal completion events. The results indicate that increased fronto-parietal activity is not a necessary correlate of conscious and attended perception. We speculate that fronto-parietal deactivation during non-target events may be related to the suppression of potential interference from salient, conscious, but non-goal stimuli. PMID- 28985896 TI - According to which declaration was the study conducted? PMID- 28985897 TI - Head Trauma. AB - Head trauma is a common cause of significant morbidity and mortality in dogs and cats. Traumatic brain injury may occur after head trauma. Understanding the pathophysiology of primary and secondary injury after head trauma is essential for management. This article reviews the pathophysiology of head trauma, patient assessment and diagnostics, and treatment recommendations. PMID- 28985898 TI - The impact of transcatheter aortic valve implantation on quality of life: A mixed methods study. AB - OBJECTIVE: To provide an in-depth understanding of patients' views about the impact of transcatheter aortic valve implantation on self-reported quality of life. BACKGROUND: Transcatheter aortic valve implantation is considered to be the gold standard of care for inoperable patients diagnosed with severe symptomatic aortic stenosis. Mid- to long-term clinical outcomes are favourable and questionnaire data indicates improvements in quality of life but an in-depth understanding of how quality of life is altered by the intervention is missing. METHODS: A mixed methods study design with a total of 89 in-depth qualitative interviews conducted with participants (39% male; mean age 81.7 years), 1 and 3 months post TAVI, recruited from a regional centre in England. Data were triangulated with questionnaire data (SF-36 and EQ5D-VAS) collected, pre, 1 and 3 months post implantation. RESULTS: Participants' accounts were characterised by four key themes; shortened life, extended life, limited life and changed life. Quality of life was changed through two mechanisms. Most participants reported a reduced symptom burden and all explained that their life expectancy was improved. Questionnaire data supported interview data with gradual improvements in mean EQ 5D scores and SF-36 physical and mental domain scores at 1 and 3 months compared to baseline. CONCLUSION: Findings suggest that TAVI was of variable benefit, producing considerable improvements in either mental or physical health in many participants, while a smaller proportion continued to deteriorate. PMID- 28985899 TI - Treatment of Extensive Gluteus Muscle Tears With Transosseous Fixation and a Nonresorbable Collagen Patch. AB - BACKGROUND: Extensive tearing of the gluteus muscles (spontaneous or subsequent to hip arthroplasty) is difficult to treat. We are carrying out osseous fixation with securement of the suture anchor by a nonresorbable collagen patch. The objective of this study is to examine the follow-up data of 30 patients and to assess whether the clinical outcomes depended on the extent of the fatty degeneration of the gluteus medius. METHODS: Thirty patients (28 female and 2 male) with a mean age of 76.8 +/- 4.3 years (68-83 years) were followed for a mean of 46.8 +/- 23.1 months (24-101 months). RESULTS: Pain improved significantly from a preoperative visual analog scale score of 7.0 +/- 1.52 (6 10) to 0.83 +/- 0.77 (0-3) 24-month postoperative. The gluteus medius muscle force increased from 2.09 +/- 0.81 to 3.3 +/- 0.78 using the British Medical Research Council Scale. All patients exhibited a severe limp before the operation. Postoperatively, only 5 patients had a severe limp, while 14 exhibited a mild limp and 11 no limp at all. The modified Harris Hip Score increased from a preoperative value of 44.5 +/- 4.2 (26-66) to a value of 81.1 +/- 7.79 (60-100) 24-month postoperative. The functional results were dependent on the level of fatty degeneration of the muscle. CONCLUSION: The first results for this surgical technique appear to be very promising for the treatment of extensive tearing of the gluteus musculature that has a degree of fatty degeneration less than 75%. PMID- 28985900 TI - Clinical and microbiological findings of septic arthritis caused by Haemophilus parainfluenzae. AB - OBJECTIVES: To report a case of septic arthritis due to H. parainfluenzae and to review the clinical and microbiological characteristics of published case patients. PATIENTS AND METHODS: Data was collected on age, sex, infection localization, underlying risk factors, symptom onset-diagnosis interval, analytical findings, microbiological diagnosis, treatment, outcome, and follow-up of the present patient (presenting with septic arthritis of the pubic symphysis due to H. parainfluenzae) and those identified in a literature analysis. RESULTS: Data of 18 patients, including 17 reported case patients, was collected. Mean age at presentation was 51+/-9 years. Underlying diseases for septic arthritis were recorded in 11 patients. The infection site was the knee in eight patients, hip and/or acromioclavicular joint in five. Pain was observed in 15 patients and fever in 10; the mean symptom onset-diagnosis interval was 9.4 days. Diagnosis was obtained from synovial fluid aspirate in 12 patients and from blood cultures in four. Susceptibility of H. parainfluenzae strains was reported in 12 cases. Eight patients were treated with cephalosporins and 10 with penicillins. A favorable outcome was observed in 13 patients. CONCLUSIONS: Septic arthritis caused by H. parainfluenzae is a rare entity that requires a high level of suspicion before application of laboratory methods for rapid diagnosis and treatment. PMID- 28985903 TI - Quantitative analysis of aldehydes in canned vegetables using static headspace gas chromatography-mass spectrometry. AB - Volatile aldehydes appear in canned vegetables as constituents and some of them can also be present as disinfection by-products (DBPs) because of the contact between vegetables and treated water. This paper describes two static headspace gas chromatography-mass spectrometry (SHS-GC-MS) methods to determine 15 aldehydes in both the solid and the liquid phases of canned vegetables. The treatment for both phases of samples was carried out simultaneously into an SHS unit, including the leaching of the aldehydes (from the vegetable), their derivatization and volatilization of the oximes formed. Detection limits were obtained within the range of 15-400MUg/kg and 3-40MUg/L for aldehydes in the solid and the liquid phases of the food, respectively. The relative standard deviation was lower than 7% -for the whole array of the target analytes-, the trueness evaluated by recovery experiments provided %recoveries between 89 and 99% and short- and long-term stability studies indicated there was no significant variation in relative peak areas of all aldehydes in both phases of canned vegetables after their storing at 4 degrees C for two weeks. The study of the origin of the 15 aldehydes detected between both phases of canned vegetables showed that: i) the presence of 13 aldehydes -at average concentrations of 2.2 39MUg/kg and 0.25-71MUg/L for the solid and the liquid phases, respectively- is because they are natural constituents of vegetables; and ii) the presence of glyoxal and methylglyoxal -which are mainly found in the liquid phase (average values, 1.4-4.1MUg/L)- is ascribed to the use of treated water, thereby being DBPs. PMID- 28985901 TI - Systemic Manifestations in Pyridox(am)ine 5'-Phosphate Oxidase Deficiency. AB - OBJECTIVE: Pyridoxine is converted to its biologically active form pyridoxal-5 phosphate (P5P) by the enzyme pyridox(am)ine 5'-phosphate oxidase and serves as a cofactor in nearly 200 reactions in the central nervous system. Pyridox(am)ine 5' phosphate oxidase deficiency leads to P5P dependent epilepsy, typically a neonatal- or infantile-onset epileptic encephalopathy treatable with P5P or in some cases, pyridoxine. Following identification of retinopathy in a patient with pyridox(am)ine 5'-phosphate oxidase deficiency that was reversible with P5P therapy, we describe the systemic manifestations of pyridox(am)ine 5'-phosphate oxidase deficiency. METHODS: A series of six patients with homozygous mutations of PNPO, the gene coding pyridox(am)ine 5'-phosphate oxidase, were evaluated in our center over the course of two years for phenotyping of neurological and systemic manifestations. RESULTS: Five of six were born prematurely, three had anemia and failure to thrive, and two had elevated alkaline phosphatase. A movement disorder was observed in two children, and a reversible retinopathy was observed in the most severely affected infant. All patients had neonatal-onset epilepsy and were on a continuum of developmental delay to profound encephalopathy. Electroencephalographic features included background slowing and disorganization, absent sleep features, and multifocal and generalized epileptiform discharges. All the affected probands carried a homozygous PNPO mutation (c.674 G>T, c.686 G>A and c.352G>A). CONCLUSION: In addition to the well described epileptic encephalopathy, pyridox(am)ine 5'-phosphate oxidase deficiency causes a range of neurological and systemic manifestations. A movement disorder, developmental delay, and encephalopathy, as well as retinopathy, anemia, and failure to thrive add to the broadening clinical spectrum of P5P dependent epilepsy. PMID- 28985902 TI - Simultaneous determination of acrylamide and 4-hydroxy-2,5-dimethyl-3(2H) furanone in baby food by liquid chromatography-tandem mass spectrometry. AB - A liquid chromatography triple quadrupole mass spectrometry method was developed and validated for the simultaneous determination of acrylamide and 4-hydroxy-2,5 dimethyl-3(2H)-furanone (HDMF) in baby food. The sample preparation involves acetonitrile-based extraction combined with dispersive primary secondary amine (PSA) cleanup and cation-exchange solid-phase extraction (SPE), which promotes efficient removal of matrix interferences. Analytical selectivity and sensitivity were achieved for the quantification of acrylamide and HDMF in complex matrices such as fruit, cereal and milk-based baby foods; furthermore, adequate linearity (range 10-300MUgkg-1) in solvent and matrix-matched calibration curves, and appropriate recoveries (94-110%) and precision (RSD<=10%), under repeatability and within-laboratory reproducibility conditions, were also obtained. Expanded measurement uncertainty was estimated at the 20MUgkg-1 level (limit of quantification) on the basis of data obtained from in-house validation, with values of 25.5 and 16.5% for acrylamide and HDMF, respectively. The fitness for purpose of developed method was verified by analyzing 15 commercial baby foods available in the Brazilian market. Acrylamide was detected in one plum-based baby food (35MUgkg-1) while HDMF in 67% of the samples analyzed (levels between 25 and 262MUgkg-1). PMID- 28985904 TI - Facile preparation of multi-functionalized hybrid monoliths via two-step photo initiated reactions for two-dimensional liquid chromatography-mass spectrometry. AB - A facile approach was developed to prepare hybrid monoliths with different functions via two-step photo-initiated reactions. Firstly, acrylopropyl polyhedral oligomertic silsesquioxane (acryl-POSS) and propargyl acrylate (PA) were used as precursors to synthesize alkynyl-functionalized hybrid monoliths via photo-initiated free radical polymerization. Secondly, the hybrid monoliths were modified with 1-octadecanethiol (ODT) and sodium 3-mercapto-1-propanesulfonate (SMPS) via photo-initiated thiol-yne click reaction to prepare reversed-phase (RP) and strong cation-exchange (SCX) hybrid monoliths, respectively. The results of chromatographic characterization indicated that the column efficiencies for alkylbenzenes on ODT-modified hybrid monolith reached 84,000-87,700 plates per meter at the velocity of 0.58mm/s, and also revealed a retention-independent efficient performance of small molecules in isocratic elution. The SMPS-modified hybrid monolith exhibited both hydrophobicity and ion-exchange mechanisms, and the dynamic binding capacity was calculated to be 1.4*10-4MUmol/cm. Human Hela cells tryptic digest was well separated on ODT-modified hybrid monolith in one dimensional RPLC-MS/MS, and 2786 unique peptides and 685 proteins were identified. Furthermore, the SMPS-modified monolith coupled with ODT-modified monolith was used for two-dimensional separation of human Hela cells tryptic digest in SCX-RPLC-MS/MS, and the results showed that 9744 unique peptides and 2749 proteins were identified. Compared to those identified in one-dimensional RP system, the total numbers of unique peptides and proteins identified in SCX-RP system increased by 249.7% and 301.3%, respectively. PMID- 28985905 TI - The strategy for establishment of the multiple reaction monitoring based characteristic chemical profile of triterpenes in Alismatis rhizoma using two combined tandem mass spectrometers. AB - It was reported that triterpenes compounds in Alismatis rhizoma (AR) contributed to the lipid lowering effect on high fat diet (HFD)-induced hyperlipidemia. To date only 24 triterpenes (including the isomers) were characterized by LC-QTOF MS/MS due to the lack of strategies for systematic discovery, classification and identification of triterpenes in AR. In this study, an integrated strategy combining various QTOF-MS/MS and QTRAP-MS/MS scan functions was developed for systematic identification and specific characterization of triterpenes in AR and processed AR. First, MS/MS fragmentation behaviors of different types of triterpenes were investigated and their diagnostic product ions were systematically summarized for discovery and classification of triterpenes. Second, diagnostic product ions were used to filter the data acquired by UHPLC QTOF MS/MS for efficient identification of targeted triterpenes. Third, MRM-based characteristic chemical profile (CCP) of triterpenes was established using 30 MRM transitions by UHPLC-QTRAP-MS/MS. Fourth, MRM-based CCP was applied for comparative analyses of triterpenes in AR from different regions and from two other processed AR (salt processed AR and bran processed AR). Consequently, a total of 80 triterpenes including 14 novel compounds were identified in the AR, and 7 more triterpenes compounds were discovered using MRM-based CCP in the processed AR. This work is the most comprehensive characterization of triterpenes compounds in AR to date. The established MRM-based CCP of triterpenes compounds can be instructive for qualitative analyses and relative quantitative analyses of triterpenes in AR and its related medicinal products for potential applications including quality control and classification of different AR materials. PMID- 28985906 TI - NK cells and Immunotherapy. PMID- 28985907 TI - Association between preconception maternal beverage intake and in vitro fertilization outcomes. AB - OBJECTIVE: To study whether maternal intake of beverage type affects IVF outcomes. DESIGN: A prospective study. SETTING: Tertiary, university-affiliated center. PATIENT(S): Three hundred forty women undergoing IVF from 2014 through 2016 for infertility as well as for pregenetic diagnosis for autosomal recessive diseases were enrolled during ovarian stimulation and completed a questionnaire describing their usual beverage consumption. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): IVF outcomes were abstracted from medical records. Total caffeine intake was estimated by summing the caffeine content for specific beverages multiplied by frequency of intake. Associations between specific types of beverages and IVF outcomes were analyzed using Poisson and logistic regression models adjusting for possible confounders. RESULT(S): Higher intake of sugared soda was associated with lower total, mature, and fertilized oocytes and top quality embryos after ovarian stimulation. Women who consumed sugared soda had, on average, 1.1 fewer oocytes retrieved, 1.2 fewer mature oocytes retrieved, 0.6 fewer fertilized oocytes, and 0.6 fewer top-quality embryos compared with women who did not consume sugared soda. Furthermore, compared with women who did not drink sugared soda, the adjusted difference in percent of cycles resulting in live birth for women consuming 0.1-1 cups/day and >1 cup/day were -12% and -16%, respectively. No associations were found between consumption of coffee, caffeine, or diet sodas and IVF outcome. CONCLUSION(S): Sugared beverages, independent of their caffeine content, may be a bigger threat to reproductive success than caffeine and caffeinated beverages without added sugar. PMID- 28985908 TI - Effect of the male factor on the clinical outcome of intracytoplasmic sperm injection combined with preimplantation aneuploidy testing: observational longitudinal cohort study of 1,219 consecutive cycles. AB - OBJECTIVE: To evaluate the impact of the male factor on the outcomes of intracytoplasmic sperm injection (ICSI) cycles combined with preimplantation genetic testing for aneuploidies (PGT-A). DESIGN: Observational longitudinal cohort study. SETTING: Private in vitro fertilization (IVF) center. PATIENT(S): A total of 1,219 oocyte retrievals divided into five study groups according to sperm parameters: normozoospermia (N), moderate male factor (MMF), severe oligoasthenoteratozoospermia (OAT-S), obstructive azoospermia (OA), and nonobstructive azoospermia (NOA). INTERVENTION(S): ICSI with ejaculated/surgically retrieved sperm, blastocyst culture, trophectoderm-based quantitative polymerase chain reaction PGT-A, and frozen-warmed euploid embryo transfer (ET). MAIN OUTCOMES MEASURE(S): The primary outcome measures were fertilization, blastocyst development, and euploidy rates; the secondary outcome measures were live birth and miscarriage rates. Perinatal and obstetrical outcomes were monitored as well. RESULT(S): A total of 9,042 metaphase II oocytes were inseminated. The fertilization rate was significantly reduced in MMF, OAT-S, OA, and NOA compared with N (74.8%, 68.7%, 67.3%, and 53.1% vs. 77.2%). The blastocyst rate per fertilized oocyte was significantly reduced in MMF and NOA compared with N (48.6% and 40.6% vs. 49.3%). The timing of blastocyst development also was affected in OA and NOA. Logistic regression analysis adjusted for confounders highlighted NOA as a negative predictor of obtaining an euploid blastocyst per OPU (odds ratio 0.5). When the analysis was performed per obtained blastocyst, however, no correlation between male factor and euploidy rate was observed. Embryo transfers also resulted in similar live birth and miscarriage rates. No impact of sperm factor on obstetrical/perinatal outcomes was observed. CONCLUSION(S): Severe male factor impairs early embryonic competence in terms of fertilization rate and developmental potential. However, the euploidy rate and implantation potential of the obtained blastocysts are independent from sperm quality. PMID- 28985910 TI - Depression, assisted reproductive technology/in vitro fertilization and selective serotonin reuptake inhibitors. PMID- 28985909 TI - Neutral effect of body mass index on implantation rate after frozen-thawed blastocyst transfer. AB - OBJECTIVE: To examine the effects of body mass index (BMI) on implantation rate after uniform protocol frozen-thawed blastocyst transfer in women with a homogenous uterine environment. DESIGN: Retrospective cohort study. SETTING: Single IVF clinic at a large academic institution. PATIENT(S): Four hundred sixty one infertile women treated at a large academic institution from January 2007 to January 2014. INTERVENTION(S): All women underwent standardized slow frozen thawed blastocyst transfers with good-quality day 5-6 embryos, following an identical hormonal uterine preparation, with comparison groups divided according to BMI category: underweight (<18.5 kg/m2), normal weight (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2), and obese (>=30.0 kg/m2). MAIN OUTCOME MEASURE(S): Implantation rate. RESULT(S): There were no statistically significant differences identified when comparing implantation rates among the four BMI cohorts. The implantation rate was 38.2% in normal weight patients, 41.7% in underweight patients, 45.1% in overweight patients, and 34.7% in obese patients. Adjusted odds ratios (OR) demonstrated no association between the main outcome, implantation rate, and BMI. Compared with the normal weight patients, the adjusted OR of implantation was 1.70 (95% confidence interval [CI], 0.40-7.72) for underweight patients, 1.61 (95% CI, 0.97-2.68) for overweight patients, and 0.92 (95% CI, 0.49-1.72) for obese patients. Secondary outcomes, including rates of miscarriage, clinical pregnancy, ongoing pregnancy, and live birth, were not significantly different between cohorts. While powered to detect a 16% difference between overweight and normal weight women, the study was underpowered to detect differences in the underweight and obese women, and no definitive conclusions can be drawn for these small cohorts. Patients with transfers that required the longest amount of time, greater than 200 seconds, had the highest average BMI of 27.5 kg/m2. CONCLUSION(S): Under highly controlled circumstances across 7 years of data from a single institution, using a uniform uterine preparation, following a precise transfer technique with high-quality day 5-6 slow frozen-thawed blastocysts, a BMI in the overweight range of 25-29.9 kg/m2 is not associated with a poorer implantation rate or live-birth rate, nor is it associated with an increased risk of miscarriage when compared with a normal BMI range. The increased length of time required during transfer for women with higher BMI suggests body habitus may contribute to difficult transfers, although this may not translate into poorer implantation rates. By using a standardized protocol for slow freezing and thawing of embryos, using identical hormonal preparation and a uniform ET protocol, a homogenous uterine environment was created in this carefully selected cohort of women, thereby minimizing confounders and uniquely highlighting the neutral effect of overweight BMI on implantation rate. PMID- 28985911 TI - Hip fractures and Parkinson's disease: A case series. AB - There are no specific guidelines for treating Parkinson's disease patients who present with a hip fracture. Here we present a large cohort of patients with Parkinson's disease who suffered hip fractures. Our aim was to assess for differences between a Parkinson's disease population and a non-Parkinson's disease population with hip fractures and make recommendations on management guidelines. We performed a comprehensive analysis of prospectively collected data on all patients with hip fracture who were admitted into our department over a period of 29 years. In total 9225 patients with hip fractures were included in this study, 452 (4.9%) patients had Parkinson's disease. The mobility scores were worse pre- and post-operatively in the Parkinson's group as were mini-mental scores and ASA grade. Post-operative complications were similar between the two groups, with no difference in dislocation rate or wound complications. However, other outcomes including mobility and mortality rate at 1year were worse in the Parkinson's group. These patients also had a longer hospital stay and were more likely to be immobile and discharged to an institution. We recommend that Parkinson's disease patients should be assessed more thoroughly in the peri operative period and arrangement for rehab and discharge planning should commence as soon as possible following admission. The consent process should reflect longer hospital stays, worse mobility, higher mortality and increased likelihood of discharge to institution but concern over increased complications, specifically dislocation was not evident in our data. PMID- 28985912 TI - Patterns of vasopressor utilization during the resuscitation of massively transfused trauma patients. AB - BACKGROUND: The use of vasopressors (VP) in the resuscitation of massively transfused trauma patients might be considered a marker of inadequate resuscitation. We sought to characterize the utilization of VP in patients receiving massive transfusion and examine the association of their use with mortality. METHODS: Trauma patients admitted from January 2011 to October 2016 receiving massive transfusion, defined as 3 units of pRBC within the first hour from admission, were selected for analysis. Demographics, admission vital signs and labs, use of VP, surgical interventions and outcomes were collected. Standard statistical tools were utilized. RESULTS: Over the 5-year study period, 120 trauma patients met inclusion criteria. The median age was 39 years with 77% being male and 41% sustaining a penetrating injury. Patients who received VP [VP (+)] were more likely to have a lower admission GCS (median 4.5 vs. 14.0, p <0.01) and less likely to have a penetrating injury (31% vs. 54%, p=0.02). The overall mortality was 49% and significantly higher in the VP (+) cohort (60% vs. 34%, AHR: 9.9, adjusted p=0.03). Mortality increased in a stepwise fashion with increasing number of VP utilized, starting at 34% for no VP, to 78% for 3 VP, and 100% for 5 or more. The majority of deaths in the VP (-) group (88%) occurred within one day from admission. For the VP (+) group, 57% of deaths occurred within one day, with the remaining 43% occurring at a later time. CONCLUSION: In the era of massive transfusion protocols, vasopressors are commonly utilized in exsanguinating trauma patients and their use is associated with a higher mortality risk. Deaths in patients receiving vasopressors are more likely to occur later compared to those in patients who do not receive vasopressors. Further research to characterize the role of these agents in the resuscitation of trauma patients is required. PMID- 28985913 TI - Factors influencing disaster nursing core competencies of emergency nurses. AB - BACKGROUND: Emergency nurses are expected to provide required nursing services by using their professional expertise to reduce the risk posed by disasters. Thus, emergency nurses' disaster nursing core competencies are essential for coping with disasters. The purpose of the study reported here was to identify factors influencing the disaster nursing core competencies of emergency nurses. METHODS: A survey was conducted among 231 emergency nurses working in 12 hospitals in South Korea. Data were collected on disaster-related experience, attitude, knowledge, and disaster nursing core competencies by means of a questionnaire. RESULTS: In multiple regression analysis, disaster-related experience exerted the strongest influence on disaster nursing core competencies, followed by disaster related knowledge. The explanatory power of these factors was 25.6%, which was statistically significant (F=12.189, p<0.001). CONCLUSIONS: These findings indicate that the disaster nursing core competencies of emergency nurses could be improved through education and training programs that enhance their disaster preparedness. The nursing profession needs to participate actively in the development of disaster nursing education and training programs. PMID- 28985915 TI - A theoretical framework to guide a study exploring cancer related fatigue. PMID- 28985914 TI - A multinational qualitative investigation of the perspectives and drivers of exercise and dietary behaviors in people living with HIV. AB - Globally, people living with HIV (PLWH) are at remarkably high risk for developing chronic comorbidities. While exercise and healthy eating reduce and mitigate chronic comorbidites, PLWH like many others, often fail to engage in recommended levels. We qualitatively examined the perspectives and contextual drivers of diet and exercise reported by PLWH and their health care providers. Two hundred and six participants across eight sites in the United States, Puerto Rico and Botswana described one overarching theme, Arranging Priorities, and four subthemes Defining Health, Perceived Importance of Diet and Exercise, Competing Needs, and Provider Influence. People living with HIV and their health care providers recognize the importance of eating a healthy diet and engaging in regular exercise. Yet there are HIV-specific factors limiting these behaviors that should be addressed. Health care providers have an important, and often underutilized opportunity to support PLWH to make improvements to their exercise and diet behavior. PMID- 28985916 TI - Racial and ethnic differences in breastfeeding, maternal knowledge, and self efficacy among low-income mothers. AB - PURPOSE: The purpose of this secondary analysis was to examine racial and ethnic differences in the propensity to engage in breastfeeding, maternal knowledge, and self-efficacy in infant feeding among three groups of low-income mothers: non Hispanic (NH) White, NH African American, and Hispanic. BACKGROUND: While racial and ethnic differences in infant feeding practices are substantial, these differences have not been broadly examined in relation to breastfeeding, maternal knowledge, and self-efficacy in infant feeding among low-income mothers. METHODS: This secondary analysis used baseline data from a randomized clinical trial with a sample of 540 low-income, mother-infant dyads from Michigan and Colorado. All data were collected when infants were approximately one month old via self-report questionnaires. RESULTS: After adjusting for mothers' age, education, marital and working status, the odds of engaging in any form of breastfeeding among Hispanic mothers remained significantly higher than among NH African-American mothers (OR=2.5, 95% CI:1.59-3.96) and NH White mothers (OR=1.7, 95% CI:1.08-2.81). However, Hispanic mothers had significantly lower maternal knowledge and self efficacy in infant feeding than the other two groups. No significant correlations were found between maternal knowledge, self-efficacy in infant feeding, and the propensity to breastfeed. CONCLUSIONS: Racial and ethnic variations were evident in the propensity to breastfeed, maternal knowledge, and self-efficacy in infant feeding suggesting the importance of tailoring breastfeeding programs to improve breastfeeding, and associated positive health outcomes. Further investigation is needed to find a better way to address breastfeeding disparity in relation to race and ethnicity, maternal knowledge, and self-efficacy in infant feeding. PMID- 28985917 TI - Effect of aromatherapy via inhalation on the sleep quality and fatigue level in people undergoing hemodialysis. AB - The most common problems in hemodialysis patients are sleep disorders and fatigue. This randomized-controlled experimental study was conducted to determine the effect of aromatherapy applied by inhalation on sleep quality and fatigue level in hemodialysis patients. The study was completed in five hemodialysis centers settled in two provinces with 27 intervention group patients and 35 controls, being totally 62 patients, recruited with simple randomization. Ethical approval, informed consent from the individuals and institutional permission were obtained. Data were collected with a questionnaire form and Visual Analogue Scale (VAS) for fatigue, Piper fatigue scale, Pittsburgh Sleep Quality Index (PSQI), and follow-up forms for the patient and the researcher. Aromatherapy inhalation (sweet orange and lavender oil) was performed before going to bed every day for one month to the intervention group patients. No other application has been made to the control group patients except for standard hemodialysis treatment. All of the forms were performed at baseline and at follow-up at the end of the four weeks (baseline and last follow-up), VAS and Piper fatigue scale were performed during follow-ups at the end of every week (the first, second and third follow ups). Data were statistically analyzed with Independent Samples t-test, one way analysis of variance, Pearson correlation analysis, chi-square test, Friedman and Mann Whitney U tests and Bonferroni test. p<0.05 was set as statistically significant in comparisons. Mean total and sub-dimension scores of VAS, Piper fatigue scale and PSQI (except for daytime sleepiness dysfunction sub-dimension) of the intervention and control groups at baseline were not significantly different (p>0.05). It was found that mean total and sub-dimension scores of VAS, Piper fatigue scale and PSQI of the intervention group significantly decreased in other follow-ups compared to the control group (p<0.05). Consequently, it was determined that aromatherapy applied by inhalation improved sleep quality, decreased fatigue level and severity in hemodialysis patients. Accordingly, aromatherapy prepared with sweet orange and lavender oil may be recommended to increase sleep quality and to decrease fatigue level of the hemodialysis patients. PMID- 28985918 TI - Longitudinal examination of social and environmental influences on motivation for physical activity. AB - BACKGROUND: Physical activity behavior is influenced by numerous factors including motivation, social interactions, and the walkability of the environment. AIM: To examine how social contexts and environmental features affect physical activity motivational processes across time. METHODS: Participants (N=104) completed 3 monthly online surveys assessing self determination theory constructs, social partners in physical activity, neighborhood walkability, and weekly physical activity. Longitudinal path analysis examined the degree to which physical activity was predicted by individual goals, orientation, and autonomy support and whether these associations were meditated by motivation and moderated by the social and environmental contexts of physical activity. RESULTS: The effect of controlled exercise orientations on physical activity was mediated by autonomous motivation. This association was stronger among those who perceived less crime in their neighborhoods. DISCUSSION: To improve the ability to tailor physical activity counseling it is important to understand how each person views exercise situations and to understand his/her social and neighborhood environments. PMID- 28985919 TI - Contributing factors of teenage pregnancy among African-American females living in economically disadvantaged communities. AB - AIM: To identify contributing factors that increased the risk of pregnancy among African-American adolescent females living in economically disadvantaged communities and to evaluate the current pregnancy prevention programs addressing these factors in order to provide suggestions for the development of tailored pregnancy prevention programs for this target population. BACKGROUND: Pregnancy rates among adolescents in the United States have declined over the past several years. Despite this trend, the pregnancy rate for African-American adolescent females is disproportionately higher than the adolescent pregnancy rates for other ethnicities. Limited attempts have been made to compile and synthesize the factors that increase risk of pregnancy in this population or to evaluate the effectiveness of intervention programs for African-American females that incorporate these risk factors. METHOD: An integrative literature review was conducted to identify the major contributing factors of pregnancy among African American adolescents living in economically disadvantaged areas. RESULTS: Of the identified contributing risk factors for early pregnancy among African-American adolescent females, the five most supported risk factors were: parental influence, peer influence, social messages, substance use including alcohol, and pregnancy desire. Twelve pregnancy prevention programs were identified that addressed one or more of the five contributing factors to pregnancy. Parental influence and social messages were the most addressed factors among these programs. CONCLUSIONS: This review found five contributing factors related to teenage pregnancy; however, current intervention programs are not well addressed substance use as a component of alcohol use. Thus, development of a tailored pregnancy prevention program incorporating those factors will help decrease the high pregnancy rate among this target population. PMID- 28985920 TI - Comparing appropriateness and equivalence of email interviews to phone interviews in qualitative research on reproductive decisions. AB - BACKGROUND: Despite an increasing use of qualitative email interviews by nurse researchers, there is little understanding about the appropriateness and equivalence of email interviews to other qualitative data collection methods, especially on sensitive topics research. PURPOSE: The purpose is to describe our procedures for completing asynchronous, email interviews and to evaluate the appropriateness and equivalency of email interviews to phone interviews in two qualitative research studies that examined reproductive decisions. METHODS: Content analysis guided the methodological appraisal of appropriateness and equivalency of in-depth, asynchronous email interviews to single phone interviews. Appropriateness was determined by: (a) participants' willingness to engage in email or phone interviews, (b) completing data collection in a timely period, and (c) participants' satisfaction with the interview. Equivalency was evaluated by: (a) completeness of the interview data, and (b) insight obtained from the data. RESULTS: Of the combined sample in the two studies (N=71), 31% of participants chose to participate via an email interview over a phone interview. The time needed to complete the email interviews averaged 27 to 28days and the number of investigator probe-participant response interchanges was 4 to 5cycles on average. In contrast, the phone interviews averaged 59 to 61min in duration. Most participants in both the email and phone interviews reported they were satisfied or very satisfied with their ability to express their true feelings throughout the interview. Regarding equivalence, 100% of the email and phone interviews provided insight into decision processes. Although insightful, two of the email and one phone interview had short answers or, at times, underdeveloped responses. Participants' quotes and behaviors cited within four published articles, a novel evaluation of equivalency, revealed that 20% to 37.5% of the citations about decision processes were from email participants, which is consistent with the percent of email participants. CONCLUSIONS: In-depth, asynchronous email interviews were appropriate and garnered rich, insightful data that augmented the phone interviews. Awareness of the procedures, appropriateness, and nuances when carrying out email interviews on sensitive topics may provide nurse researchers with the ability to obtain thick, rich data that can best advance clinical practice and direct future research. PMID- 28985922 TI - End of life care in nursing homes in Spain: Exploratory analysis and evidences of validity of a new scale. AB - Quality end-of-life care is a central issue in nursing homes, requiring the assessment of individual and family needs by health professionals. Although previous instruments have been developed, they usually rely on family reports and have been adapted from other clinical contexts (hospital or primary care). It is important to consider how health care professionals working in nursing homes perceive what is necessary to achieve quality end-of-life care. In this study, the objective was to develop an instrument to assess quality of end-of-life care in the context of Spanish care homes. A 24 item scale Nursing Home End of Life Care Scale (NHEOLC) was developed through a systematic evaluation of existing tools combined with an iterative process of consultation with group experts in end of life care in long term care settings. A total of 307 health care professionals agreed to participate in the study and completed the scale. The scale was grouped in six dimensions: physical, psychological aspects and spiritual aspects of care, family care, bereavement, and patient/family preferences management. The results suggest an adequate factorial structure of the scale and good internal consistency for the total score and the subscales. In addition, the results showed significant differences depending on the size of the nursing home, the category of health professionals, and their own perceptions of his work regarding end-of-life care. PMID- 28985921 TI - Using a mixed methods approach to explore factors associated with evidence-based cancer pain management practice among nurses. PMID- 28985926 TI - How Art Can Educate the Radiologist's Eye: Duchamp's "Nude Descending a Staircase". PMID- 28985923 TI - Use of the Hage framework for theory construction: Factors affecting glucose control in the college-aged student with type 1 diabetes. AB - This article describes the Hage framework for theory construction and its application to the clinical problem of glycemic control in college-aged students with type 1 diabetes. College-aged students with type 1 diabetes struggle to self manage their condition. Glycated hemoglobin (HbA1c), if controlled within acceptable limits (6-8%), is associated with the prevention or delay of serious diabetic complications such as kidney and cardiovascular disease. Diabetes educators provide knowledge and skills, but young adults must self-manage their condition on a daily basis, independent of parents. The Hage framework includes five tasks of theory construction: narrowing and naming the concepts, specifying the definitions, creating the theoretical statements, specifying the linkages, and ordering components in preparation for model building. During the process, concepts within the theory were revised as the literature was reviewed, and measures and hypotheses, foundational to research, were generated. We were successful in applying the framework and creating a model of factors affecting glycemic control, emphasizing that physical activity, thought of as a normal part of wellness, can be a two-edged sword producing positive effect but also serious negative effects in some college-aged students with type 1 diabetes. Contextual factors important to self-management in college-aged students are emphasized. The Hage framework, already used to a small extent in nursing curricula, deserves more attention and, because of its generic nature, may be used as a template for theory construction to examine a wide variety of nursing topics. PMID- 28985924 TI - Narrative Nursing: Applications in Practice, Education, and Research. PMID- 28985925 TI - Improving Performance of Breast Cancer Risk Prediction by Incorporating Optical Density Image Feature Analysis: An Assessment. AB - RATIONALE AND OBJECTIVES: The purpose of this study is to improve accuracy of near-term breast cancer risk prediction by applying a new mammographic image conversion method combined with a two-stage artificial neural network (ANN)-based classification scheme. MATERIALS AND METHODS: The dataset included 168 negative mammography screening cases. In developing and testing our new risk model, we first converted the original grayscale value (GV)-based mammographic images into optical density (OD)-based images. For each case, our computer-aided scheme then computed two types of image features representing bilateral asymmetry and the maximum of the image features computed from GV and OD images, respectively. A two stage classification scheme consisting of three ANNs was developed. The first stage included two ANNs trained using features computed separately from GV and OD images of 138 cases. The second stage included another ANN to fuse the prediction scores produced by two ANNs in the first stage. The risk prediction performance was tested using the rest 30 cases. RESULTS: With the two-stage classification scheme, the computed area under the receiver operating characteristic curve (AUC) was 0.816 +/- 0.071, which was significantly higher than the AUC values of 0.669 +/- 0.099 and 0.646 +/- 0.099 achieved using two ANNs trained using GV features and OD features, respectively (P < .05). CONCLUSION: This study demonstrated that applying an OD image conversion method can acquire new complimentary information to those acquired from the original images. As a result, fusion image features computed from these two types of images yielded significantly higher performance in near-term breast cancer risk prediction. PMID- 28985927 TI - Association Between Targeted HER-2 Therapy and Breast Reconstruction Outcomes: A Propensity Score-Matched Analysis. AB - BACKGROUND: Current treatment for HER-2+ breast cancer includes chemotherapy and targeted HER-2 therapy with trastuzumab and/or pertuzumab. Evidence is lacking on the safety of breast reconstructive operations in these patients. We hypothesized that targeted HER-2 therapy was not associated with post-mastectomy reconstructive outcomes. STUDY DESIGN: Women receiving chemotherapy and post mastectomy reconstruction at Duke University Medical Center from 2006 to 2016 were retrospectively identified. Patients receiving targeted HER-2 therapy with trastuzumab and/or pertuzumab within 6 weeks before breast reconstruction were propensity score-matched 1:1 to patients who did not receive targeted HER-2 therapy, based on the following factors: age, obesity, diabetes, tobacco use, receipt of neoadjuvant chemotherapy, chemotherapy regimen, and radiation therapy. Primary study outcomes included the occurrence of hematoma, seroma, infection, wound breakdown, mastectomy skin flap necrosis, and postoperative flap thrombosis. RESULTS: A total of 481 women were identified, resulting in 107 propensity score-matched pairs. Administration of combined trastuzumab and pertuzumab therapy before breast reconstruction was independently associated with increased risk of postoperative wound breakdown requiring operative intervention for closure, compared with patients not undergoing targeted HER-2 therapy (odds ratio 65.29; 95% CI 1.63 to 2,611.50; p = 0.03). In addition, larger tumor size (2 to 5 cm) was significantly associated with a reduced risk of postoperative wound breakdown, compared with smaller tumors (<2 cm) (odds ratio 0.41; 95% CI 0.19 to 0.87; p = 0.02). Single-agent targeted HER-2 therapy with trastuzumab was not significantly associated with reconstructive complications. CONCLUSIONS: Our study suggests that trastuzumab therapy in conjunction with breast reconstructive operation is not associated with reconstructive complications, and breast reconstruction does not need to be delayed due to the administration of trastuzumab. Future studies are needed to evaluate the impact of pertuzumab on surgical outcomes. PMID- 28985930 TI - A Review of Resting-State Analysis Methods. AB - Resting-state functional connectivity is the synchronization of brain regions with each another. Alterations are suggestive of neurologic or psychological disorders. This article discusses methods and approaches used to describe resting state brain connectivity and the results in neurotypical and diseased brains. PMID- 28985928 TI - Methods and Considerations for Dynamic Analysis of Functional MR Imaging Data. AB - Functional MR imaging (fMR imaging) studies have recently begun to examine spontaneous changes in interregional interactions (functional connectivity) over seconds to minutes, and their relation to natural shifts in cognitive and physiologic states. This practice opens the potential for uncovering structured, transient configurations of coordinated brain activity whose features may provide novel cognitive and clinical biomarkers. However, analysis of these time-varying phenomena requires careful differentiation between neural and nonneural contributions to the fMR imaging signal and thorough validation and statistical testing. In this article, the authors present an overview of methodological and interpretational considerations in this emerging field. PMID- 28985929 TI - Ten Key Observations on the Analysis of Resting-state Functional MR Imaging Data Using Independent Component Analysis. AB - For more than 20 years, the powerful, flexible family of independent component analysis (ICA) techniques has been used to examine spatial, temporal, and subject variation in functional magnetic resonance (fMR) imaging data. This article provides an overview of 10 key principles in the basic and advanced application of ICA to resting-state fMR imaging. ICA's core advantages include robustness to artifact; false-positives and autocorrelation; adaptability to variant study designs; agnosticism to the temporal evolution of fMR imaging signals; and ability to extract, identify, and analyze neural networks. ICA remains in the vanguard of fMRI methods development. PMID- 28985931 TI - Graph Theoretic Analysis of Resting State Functional MR Imaging. AB - Graph theoretic analyses applied to examine the brain at rest have played a critical role in clarifying the foundations of the brain's intrinsic and task related activity. There are many opportunities for clinical scientists to describe and predict dysfunction using a network perspective. This primer describes the theoretic basis and practical application of graph theoretic analysis to resting state functional MR imaging data. Major practices, concepts, and findings are concisely reviewed. The theoretic and practical frontiers of resting state functional MR imaging are highlighted with observations about major avenues for conceptual advances and clinical translation. PMID- 28985932 TI - Machine Learning Applications to Resting-State Functional MR Imaging Analysis. AB - Machine learning is one of the most exciting and rapidly expanding fields within computer science. Academic and commercial research entities are investing in machine learning methods, especially in personalized medicine via patient-level classification. There is great promise that machine learning methods combined with resting state functional MR imaging will aid in diagnosis of disease and guide potential treatment for conditions thought to be impossible to identify based on imaging alone, such as psychiatric disorders. We discuss machine learning methods and explore recent advances. PMID- 28985933 TI - Resting-state Functional Magnetic Resonance Imaging in Presurgical Functional Mapping: Sensorimotor Localization. AB - This article compares resting-state functional magnetic resonance (fMR) imaging with task fMR imaging for presurgical functional mapping of the sensorimotor (SM) region. Before tumor resection, 38 patients were scanned using both methods. The SM area was anatomically defined using 2 different software tools. Overlap of anatomic regions of interest with task activation maps and resting-state networks was measured in the SM region. A paired t-test showed higher overlap between resting-state maps and anatomic references compared with task activation when using a maximal overlap criterion. Resting state-derived maps are more comprehensive than those derived from task fMR imaging. PMID- 28985934 TI - Application of Resting State Functional MR Imaging to Presurgical Mapping: Language Mapping. AB - Resting state functional MR imaging (rs-fMR imaging) has become an indispensable tool for examining brain function. The greatest opportunity to translate rs-fMR imaging from the research domain into clinical use is as a tool for examining intrinsic brain networks for preoperative planning. Many studies have demonstrated concordance of intrinsic motor networks from rs-fMR imaging data with task-fMR imaging and direct cortical stimulation. Earlier reports show concordance of language networks as well, although more recent studies with larger numbers of subjects demonstrate subject-level variability that needs to be further investigated and addressed before widespread implementation of rs-fMR imaging for preoperative planning. PMID- 28985936 TI - Applications of Resting-State Functional Connectivity to Neurodegenerative Disease. AB - Neurodegenerative diseases target specific large-scale neuronal networks, leading to distinct behavioral and cognitive dysfunctions. Resting-state functional magnetic resonance imaging (rsfMR imaging)-based functional connectivity method maps symptoms-associated functional network deterioration in vivo. This article summarizes accumulating functional connectivity findings supporting the network based neurodegeneration hypothesis. Understanding of disease mechanism can further guide early detection and predictions of disease progression and inform development of more effective treatment. With better clinical phenotyping and larger samples across multiple sites, we discuss several possible future directions to further develop rsfMR imaging-based functional connectivity methods into scientifically and clinically useful assays for neurodegenerative disorders. PMID- 28985935 TI - Limitations of Resting-State Functional MR Imaging in the Setting of Focal Brain Lesions. AB - Methods of image acquisition and analysis for resting-state functional MR imaging (rsfMR imaging) are still evolving. Neurovascular uncoupling and susceptibility artifact are important confounds of rsfMR imaging in the setting of focal brain lesions such as brain tumors. This article reviews the detection of these confounds using rsfMR imaging metrics in the setting of focal brain lesions. In the near future, with the wide range of ongoing research in rsfMR imaging, these issues likely will be overcome and will open new windows into brain function and connectivity. PMID- 28985937 TI - Applications of Resting State Functional MR Imaging to Traumatic Brain Injury. AB - Traumatic brain injury (TBI) is an important public health issue. TBI includes a broad spectrum of injury severities and abnormalities. Functional MR imaging (fMR imaging), both resting state (rs) and task, has been used often in research to study the effects of TBI. Although rs-fMR imaging is not currently applicable in clinical diagnosis of TBI, computer-aided tools are making this a possibility for the future. Specifically, graph theory is being used to study the change in networks after TBI. Machine learning methods allow researchers to build models capable of predicting injury severity and recovery trajectories. PMID- 28985938 TI - Applications of Resting-State Functional MR Imaging to Epilepsy. AB - We discuss the value of resting-state functional MR imaging (rsfMR imaging) as an emerging technique to address questions about memory and language that are central in surgery for temporal-lobe epilepsy, namely the identification and characterization of eloquent cortex to avoid surgical morbidity. The emergence of a robust set of data using rsfMR imaging has opened new avenues for exploring more direct relationships between neural networks and current cognitive function and prediction of postoperative change. These techniques are also being explored for their potential to characterize epilepsy subtypes, identify epileptic foci, and monitor treatment effects. PMID- 28985940 TI - Functional Connectivity. PMID- 28985941 TI - Functional Connectivity. PMID- 28985939 TI - Applications of Resting State Functional MR Imaging to Neuropsychiatric Diseases. AB - Resting state studies in neuropsychiatric disorders have already provided much useful information, but the field is regarded as being at a relatively preliminary stage and subject to several design issues that set limits on the overall utility. PMID- 28985942 TI - Effects of Pyridostigmine bromide on SH-SY5Y cells: An in vitro neuroblastoma neurotoxicity model. AB - Pyridostigmine bromide (PB) is a reversible acetylcholinesterase (AChE) inhibitor and the first-choice for the treatment of symptoms associated with myasthenia gravis and other neuromuscular junction disorders. However, evidence suggested that PB could be associated with the Gulf War Illness characterised by the presence of fatigue, headaches, cognitive dysfunction, and musculoskeletal respiratory and gastrointestinal disturbances. Given that a potential neurotoxic effect of PB has not yet been completely elucidated, the present investigation used neural SH-SY5Y cells to evaluate the effect of PB on the cellular viability, cell apoptosis, modulation of the cell cycle, oxidative stress, and genotoxicity variables, which indicate neurodegeneration. As expected, a PB concentration curve based on the therapeutic dose of the drug showed an inhibition of the AChE activity. However, this effect was transient and did not involve differential AChE gene regulation by PB. These results confirmed that undifferentiated SH-SY5Y cells can be used as a cholinergic in vitro model. In general, PB did not trigger oxidative stress, and at a slightly higher PB concentration (80ng/mL), higher levels of protein carbonylation and DNA damage were detected, as determined by the marker 8-deoxyguanosine. The PB genotoxic effects at 80ng/mL were confirmed by the upregulation of the p53 and DNA methyltransferase 1 (DNMT1) genes, which are associated with cellular DNA repair. PB at 40ng/mL, which is the minimal therapeutic dose, led to higher cell proliferation and mitochondrial activity compared with the control group. The effects of PB were corroborated by the upregulation of the telomerase gene. In summary, despite the methodological constrains related to the in vitro protocols, our results suggested that exposure of neural cells to PB, without other chemical and physical stressors did not cause extensive toxicity or indicate any neurodegeneration patterns. PMID- 28985943 TI - No evidence of DNA damage by co-exposure to extremely low frequency magnetic fields and aluminum on neuroblastoma cell lines. AB - Whether exposure to 50-60Hz extremely low frequency magnetic fields (ELF-MF) exerts neurotoxic effects is a debated issue. Analogously, the potential role of Aluminum (Al) in neurodegeneration is a matter of controversial debate. As all living organisms are exposed to ELF-MF and/or Al daily, we found investigating the early effects of co-exposure to ELF-MF and Al in SH-SY5Y and SK-N-BE-2 human neuroblastoma (NB) cells intriguing. SH-SY5Y5 and SK-N-BE-2 cells underwent exposure to 50Hz ELF-MF (0.01, 0.1 or 1mT) or AlCl3 (4 or 40MUM) or co-exposure to 50Hz ELF-MF and AlCl3 for 1h continuously or 5h intermittently. The effects of the treatment were evaluated in terms of DNA damage, redox status changes and Hsp70 expression. The DNA damage was assessed by Comet assay; the cellular redox status was investigated by measuring the amount of reduced glutathione (GSH) and glutathione disulfide (GSSG) while the inducible Hsp70 expression was evaluated by western blot analysis and real-time RT-PCR. Neither exposure to ELF-MF or AlCl3 alone induced DNA damage, changes in GSH/GSSG ratio or variations in Hsp70 expression with respect to the controls in both NB cell lines. Similarly, co exposure to ELF-MF and AlCl3 did not have any synergic toxic effects. The results of this in vitro study, which deals with the effects of co-exposure to 50Hz MF and Aluminum, seem to exclude that short-term exposure to ELF-MF in combination with Al can have harmful effects on human SH-SY5Y and SK-N-BE-2 cells. PMID- 28985944 TI - In vitro cell transformation induced by synthetic amorphous silica nanoparticles. AB - Synthetic amorphous silica nanoparticles (SAS) are among the most widely produced and used nanomaterials, but little is known about their carcinogenic potential. This study aims to evaluate the ability of four different SAS, two precipitated, NM-200 and NM-201, and two pyrogenic, NM-202 and NM-203, to induce the transformation process. For this, we used the recently developed in vitro Bhas 42 cell transformation assay (CTA). The genome of the transgenic Bhas 42 cells contains several copies of the v-Ha-ras gene, making them particularly sensitive to tumor-promoter agents. The Bhas 42 CTA, which includes an initiation assay and a promotion assay, was validated in our laboratory using known soluble carcinogenic substances. Its suitability for particle-type substances was verified by using quartz Min-U-Sil 5 (Min-U-Sil) and diatomaceous earth (DE) microparticles. As expected given their known transforming properties, Min-U-Sil responded positively in the Bhas 42 CTA and DE responded negatively. Transformation assays were performed with SAS at concentrations ranging from 2MUg/cm2 to 80MUg/cm2. Results showed that all SAS have the capacity to induce transformed foci, interestingly only in the promotion assay, suggesting a mode of action similar to tumor-promoter substances. NM-203 exhibited transforming activity at a lower concentration than the other SAS. In conclusion, this study showed for the first time the transforming potential of different SAS, which act as tumor-promoter substances in the Bhas 42 model of cell transformation. PMID- 28985945 TI - Multi-walled carbon nanotube-induced genotoxic, inflammatory and pro-fibrotic responses in mice: Investigating the mechanisms of pulmonary carcinogenesis. AB - The International Agency for Research on Cancer has classified one type of multi walled carbon nanotubes (MWCNTs) as possibly carcinogenic to humans. However, the underlying mechanisms of MWCNT- induced carcinogenicity are not known. In this study, the genotoxic, mutagenic, inflammatory, and fibrotic potential of MWCNTs were investigated. MutaTMMouse adult females were exposed to 36+/-6 or 109+/ 18MUg/mouse of Mitsui-7, or 26+/-2 or 78+/-5MUg/mouse of NM-401, once a week for four consecutive weeks via intratracheal instillations, alongside vehicle-treated controls. Samples were collected 90days following the first exposure for measurement of DNA strand breaks, lacZ mutant frequency, p53 expression, cell proliferation, lung inflammation, histopathology, and changes in global gene expression. Both MWCNT types persisted in lung tissues 90days post-exposure, and induced lung inflammation and fibrosis to similar extents. However, there was no evidence of DNA damage as measured by the comet assay following Mitsui-7 exposure, or increases in lacZ mutant frequency, for either MWCNTs. Increased p53 expression was observed in the fibrotic foci induced by both MWCNTs. Gene expression analysis revealed perturbations of a number of biological processes associated with cancer including cell death, cell proliferation, free radical scavenging, and others in both groups, with the largest response in NM-401 treated mice. The results suggest that if the two MWCNT types were capable of inducing DNA damage, strong adaptive responses mounted against the damage, resulting in efficient and timely elimination of damaged cells through cell death, may have prevented accumulation of DNA damage and mutations at the post exposure time point investigated in the study. Thus, MWCNT-induced carcinogenesis may involve ongoing low levels of DNA damage in an environment of persisting fibres, chronic inflammation and tissue irritation, and parallel increases or decreases in the expression of genes involved in several pro-carcinogenic pathways. PMID- 28985946 TI - Ten factors for considering the mode of action of Cr(VI)-induced gastrointestinal tumors in rodents. AB - The determination of whether a chemical induces a specific cancer through a mutagenic or non-mutagenic mode of action (MOA) plays an important role in choosing between linear and nonlinear low-dose extrapolation to derive toxicity criteria. There is no formal framework from the U.S. EPA for determining whether environmental chemicals act through a mutagenic or non-mutagenic MOA; consequently, most such determinations are made on an ad hoc basis. Eastmond [Mutat Res 751 (2012)] recently conducted a systematic investigation of MOA determinations by U.S. and international regulatory agencies and organizations, and identified ten major factors that influence them, including toxicokinetics, in vivo genotoxicity in target organs, data quality, and evidence for alternative MOAs. We have used these ten factors to evaluate mutagenic vs. non-mutagenic MOA for gastrointestinal tumors induced by oral exposure to hexavalent chromium [Cr(VI)]. We also highlight similarities between Cr(VI) and other intestinal carcinogens previously determined to have non-genotoxic MOAs. Based on these analyses, we conclude that the MOA for Cr(VI) induced gastrointestinal tumors is non-mutagenic and that threshold risk assessment approaches are appropriate. PMID- 28985947 TI - Induction of the chromosomal translocation t(14;18) by targeting the BCL-2 locus with specific binding I-125-labeled triplex-forming oligonucleotides. AB - Triplex-Forming oligonucleotides (TFO) bind sequence-specific to the DNA double helix in-vitro and in-vivo and are a promising tool to manipulate genes or gene regulatory elements. TFO as a carrier molecule for short-range particle emitter such as Auger-Electron-Emitters (AEE) bear the potential to introduce radiation induced site-specific complex DNA lesions, which are known to induce chromosomal translocations. We studied gene expression, translocation frequency and protein expression in SCL-II cells after transfection with the AEE Iodine-125 (I-125) labeled TFO-BCL2 targeting the human BCL2 gene. The TFO-BCL2 binds to the BCL2 gene in close proximity to a known major-breakage-region (mbr). SCL-II cells were transfected with I-125 labeled TFO and stored for decay accumulation. Monitoring of BCL2 translocations was done with the Fluorescence-In-Situ-Hybridization (FISH) method. The utilized FISH probes were designed to detect a t(14;18) translocation of the BCL2 gene, which is a common translocation leading to an overexpression of BCL2 protein. Analysis of BCL2 gene expression levels was done via quantitative Real-Time PCR. Verification of gene expression on the protein level was analyzed by Western blotting. The relative gene expression of BCL2 in I 125-TFO-BCL2 transfected cells showed a significant up-regulation when compared to controls. Analysis of the BCL2 t(14;18) translocation frequency revealed a significant 1.8- to 2-fold increase when compared to control cells. This 2-fold increase was not reflected on the protein level. We conclude that I-125 decays within the BCL2 gene facilitate the t(14;18) chromosomal translocation in the SCL II cells and that the increased frequency contributes to the observed overall enhanced BCL2 gene expression. PMID- 28985948 TI - Metal bioaccumulation and mutagenesis in a Tradescantia clone following long-term exposure to soils from urban industrial areas and closed landfills. AB - Soil mutagens, particularly metals, may persist long after the source of pollution has been removed, representing a hazard to plants, animals, and humans in or near contaminated areas. Often, due to urban growth, previous land uses may be forgotten and hazards overlooked. We exposed Tradescantia clone #4430 plants to soil from two industrial areas (with different former uses) and two urban waste landfills in the city of Vilnius, all of which were long disused. Two modes of exposure were used: long-term exposure of growing plants in test soils for 0.5 or 1.0y, and short-term exposure of cuttings to water and dimethyl sulfoxide (DMSO) soil extracts. An increased frequency of micronuclei (MN) was observed with both modes of exposure. The concentrations of 24 metals and other elements were analyzed in the test soils and in above-ground plant parts, under both exposure modes, and the concentration coefficients (Cc) for various elements, the total contamination index (Zs) for soils and plants, and the bioaccumulation factor (BAF) for plants were calculated. These measurements allow a comparison of the contamination levels of soils and plants with equalized values. Metal accumulation levels in plants and soils showed significant differences, providing a better understanding of the genotoxicity of soils from closed landfills and highlighting the need to determine the concentrations of metals and other genotoxicants in plants in relation to genotoxicity. PMID- 28985949 TI - Emergency Nurses' Perceptions of Efficiency and Design: Examining ED Structure, Process, and Outcomes. AB - INTRODUCTION: Due to increasing demands, it is imperative for emergency departments to improve efficiency, while providing safe and effective care. Efficient and quality healthcare delivery are impacted by interactions among the emergency department's physical structure, processes, and outcomes. Examining the interrelationship between these three components is essential for assessing quality of care in the ED setting. Studies simultaneously investigating all three aspects of this model are rare. OBJECTIVES: To study examined emergency nurses' perceptions of efficiency and satisfaction with the design of a newly constructed academic emergency department through analysis of these three assessment factors. METHODS: Data were collected using observational techniques, physical measurements of walking, and staff questionnaires. Correlation analysis was employed to investigate the relationships among specific structure, process, and outcome factors. Hierarchical linear regression was conducted to understand which structure and process variables in particular were related to the dependent variable, perceptions of efficiency and staff satisfaction with design. RESULTS: Outcomes revealed that all of the structure and process factors examined in this emergency department including unit configuration, technology, lighting, visibility, patient room layout, storage, walkability, staff stress, data access, and teamwork were significantly associated with perceptions of efficiency and staff satisfaction with design. DISCUSSION: The findings suggest that the structure of the built environment can shape healthcare processes occurring within it and ultimately improve the delivery of efficient care, thus increasing both patient and staff satisfaction. As such, the designed environment has a critical impact on enhancing performance, productivity, and staff satisfaction. PMID- 28985950 TI - Moderate to high intensity statin in dialysis patients after acute myocardial infarction: A national cohort study in Asia. AB - BACKGROUND AND AIMS: Statin is not beneficial for dialysis patients but moderate to high intensity statin is beneficial for patients after acute myocardial infarction (MI). The aim of this study was to evaluate the effect of moderate to high intensity statin on mortality, cardiovascular outcomes in dialysis patients after acute MI. METHODS: Data on dialysis patients were retrieved from the National Health Insurance Research Database in Taiwan. Dialysis patients admitted for MI were selected and divided into two groups according to statin prescription or not after MI. All-cause mortality and cardiovascular outcomes after a 4-year follow-up were analyzed after propensity score matching (PSM). RESULTS: We identified 790 patients who received moderate to high intensity statin therapy and 1788 patients who did not receive any statins after acute MI and clinical outcomes were analyzed after 1:1 PSM. The benefit of statin on mortality therapy appeared from 1 year to the end of the 4-year follow-up period after hospitalization (statin group versus non-statin group: 22.9% vs. 31.1% at 1 year (HR: 0.70; 95% CI: 0.58-0.85); 48.0% vs. 55.1% at the end of the 4 years (HR: 0.76; 95% CI: 0.67-0.88)). In addition, the impact of statin therapy was stronger in patients with shock at admission (p = 0.035). There were no differences in any individual cardiovascular outcome or adverse event. CONCLUSIONS: Moderate to high intensity statin therapy might lower all-cause mortality in dialysis patients after acute MI, especially those with shock, but not influence cardiovascular outcomes and any adverse events. PMID- 28985951 TI - A generalized smith predictor for unstable time-delay SISO systems. AB - In this work, a generalization of the Smith Predictor (SP) is proposed to control linear time-invariant (LTI) time-delay single-input single-output (SISO) systems. Similarly to the SP, the combination of any stabilizing output-feedback controller for the delay-free system with the proposed predictor leads to a stabilizing controller for the delayed system. Furthermore, the tracking performance and the steady-state disturbance rejection capabilities of the equivalent delay-free loop are preserved. In order to place this contribution in context, some modifications of the SP are revisited and recast under the same structure. The features of the proposed scheme are illustrated through simulations, showing a comparison with respect to the corresponding delay-free loop, which is here considered to be the ideal scenario. In order to emphasize the feasibility of this approach, a successful experimental implementation in a laboratory platform is also reported. PMID- 28985952 TI - Usefulness of Coronary Artery Calcium to Predict Heart Failure With Preserved Ejection Fraction in Men Versus Women (from the Multi-Ethnic Study of Atherosclerosis). AB - We studied the association of coronary artery calcium (CAC) and risk of heart failure with preserved ejection fraction (HFpEF) among men and women in a multiethnic cohort. Coronary artery disease is a risk factor for development of HFpEF and assessment of subclinical atherosclerosis using CAC may allow for the early identification of patients at risk for HFpEF. We used data from the Multi Ethnic Study of Atherosclerosis. CAC was measured at baseline in all participants. Incident HFpEF was defined as heart failure hospitalization with left ventricular ejection fraction >=50%. Multivariable-adjusted Cox proportional hazards models were used to calculate HFpEF risk by CAC categories (0, 1 to 100, 101 to 300, and >300) and by CAC (continuous), stratified by gender and race/ethnicity. Of 6809 total participants, 127 incident HFpEF cases (1.8%) were ascertained. Mean age was 62 years (+/-10 years), and the participants were 53% female, 38% White, and 12% Black. In adjusted analysis, CAC >300 was associated with increased risk of HFpEF (hazard ratio [HR] 1.68, 95% confidence interval [95 CI] 1.00, 1.83); however, this was significant only in women (HR 2.82, 95% CI 1.32, 6.00 vs HR 0.91, 95% CI 0.46, 1.82 for men, interaction p = 0.03). Similarly, CAC modeled as a continuous variable was strongly predictive in women but not in men. In conclusion, measurement of CAC, a marker of coronary atherosclerosis, may stratify risk of HFpEF beyond traditional risk factors for women. Further investigation is needed to better understand potential gender differences in pathophysiology and presentation of HFpEF. PMID- 28985953 TI - Effects of biodegradable hydrogel spacer injection on contralateral submandibular gland sparing in radiotherapy for head and neck cancers. AB - Xerostomia is the most common late toxicity after head and neck radiation. We demonstrate injection of a hydrogel spacer anteriorly displacing the submandibular gland. This procedure enables reduced dose to the displaced submandibular gland in cadaveric models of oropharynx cancer treated with IMRT, with potential implications in reducing xerostomia risk. PMID- 28985954 TI - Experimental verification of dose enhancement effects in a lung phantom from inline magnetic fields. AB - BACKGROUND AND PURPOSE: To present experimental evidence of lung dose enhancement effects caused by strong inline magnetic fields. MATERIALS AND METHODS: A permanent magnet device was utilised to generate 0.95T-1.2T magnetic fields that encompassed two small lung-equivalent phantoms of density 0.3g/cm3. Small 6MV and 10MV photon beams were incident parallel with the magnetic field direction and Gafchromic EBT3 film was placed inside the lung phantoms, perpendicular to the beam (experiment 1) and parallel to the beam (experiment 2). Monte Carlo simulations of experiment 1 were also performed. RESULTS: Experiment 1: The 1.2T inline magnetic field induced a 12% (6MV) and 14% (10MV) increase in the dose at the phantom centre. The Monte Carlo modelling matched well (+/-2%) to the experimentally observed results. Experiment 2: A 0.95T field peaked at the phantom centroid (but not at the phantom entry/exit regions) details a clear dose increase due to the magnetic field of up to 25%. CONCLUSIONS: This experimental work has demonstrated how strong inline magnetic fields act to enhance the dose to lower density mediums such as lung tissue. Clinically, such scenarios will arise in inline MRI-linac systems for treatment of small lung tumours. PMID- 28985955 TI - Paraprotein deposits in the skin. AB - Cutaneous manifestations secondary to paraprotein deposits in the skin include a group of different disorders that although rare, may be the first clinical manifestation of the underlying hematologic dyscrasia. In this article we review the clinical manifestations and histopathologic findings of the processes that result from specific deposition of the paraprotein in different structures of the skin. Paraneoplastic processes frequently associated with hematologic malignancies will not be covered in this review. Some of the disorders included here result from deposition of the intact paraprotein in the skin, whereas in other cases the lesions are due to deposition of modified paraproteins in the form of amyloid substance, cryoglobulins, or crystalglobulins. Cutaneous amyloidoma refers to nodular dermal deposits of amyloid derived from immunoglobulin light chains produced by local plasma cells in the absence of systemic amyloidosis. Dermatologists and dermatopathologists should be aware of the clinical and histopathologic features of these rare disorders because sometimes the cutaneous lesions are the first sign of an underlying silent hematologic malignancy with paraproteinemia. PMID- 28985956 TI - Psychiatric adverse events during treatment with brodalumab: Analysis of psoriasis clinical trials. AB - BACKGROUND: Individuals with psoriasis are at increased risk for psychiatric comorbidities, including suicidal ideation and behavior (SIB). OBJECTIVE: To distinguish between the underlying risk and potential for treatment-induced psychiatric adverse events in patients with psoriasis being treated with brodalumab, a fully human anti-interleukin 17 receptor A monoclonal antibody. METHODS: Data were evaluated from a placebo-controlled, phase 2 clinical trial; the open-label, long-term extension of the phase 2 clinical trial; and three phase 3, randomized, double-blind, controlled clinical trials (AMAGINE-1, AMAGINE 2, and AMAGINE-3) and their open-label, long-term extensions of patients with moderate-to-severe psoriasis. RESULTS: The analysis included 4464 patients with 9161.8 patient-years of brodalumab exposure. The follow-up time-adjusted incidence rates of SIB events were comparable between the brodalumab and ustekinumab groups throughout the 52-week controlled phases (0.20 vs 0.60 per 100 patient-years). In the brodalumab group, 4 completed suicides were reported, 1 of which was later adjudicated as indeterminate; all patients had underlying psychiatric disorders or stressors. LIMITATIONS: There was no comparator arm past week 52. Controlled study periods were not powered to detect differences in rare events such as suicide. CONCLUSIONS: Comparison with controls and the timing of events do not indicate a causal relationship between SIB and brodalumab treatment. PMID- 28985957 TI - Pediatric Guillain-Barre Syndrome: Is a low amplitude of nerve action potentials always a bad omen? PMID- 28985958 TI - A scoping review of evidence-based interventions available to parents of maltreated children ages 0-5 involved with child welfare services. AB - Parents referred to child welfare services for child maltreatment often struggle against chronic risk factors including violence, substance abuse, mental health concerns, and poverty, which impinge upon their ability to be sensitive caregivers. The first line of intervention within the child welfare context is to modify parenting behavior. This scoping review comprehensively surveyed all available literature to map the extent and range of research activity around the types of interventions available within a child welfare context to parents of infants and toddlers (0-5 years of age), to identify the facilitators and/or barriers to the uptake of interventions, and to check that interventions match the risk factors faced by parents. This scoping review engaged in stringent screening of studies based upon inclusion/exclusion criteria. Sixty-five articles involving forty-two interventions met inclusion criteria. Interventions generally aimed to improve parenting practices, the relationship between parent and child, and/or attachment security, along with reducing child abuse and/or neglect. A notable finding of this scoping review is that at present, interventions for parents of children ages 0-5 involved with the child welfare system are most frequently measured via case study and quasi-experimental designs, with randomized control trials making up 26.2% of included study designs. PMID- 28985959 TI - Introduction to a special section on Explaining Positive Adaptation of Immigrant and Minority Youth across Cultures. AB - This special section on "Explaining Positive Adaptation of Immigrant and Minority Youth across Cultures" is the result of an expert meeting organized by the Society for Research in Child Development (SRCD), the European Association of Developmental Psychology (EADP), and the European Association for Research on Adolescence (EARA). The aim of this special section was to bring together empirical studies and expert commentaries on a pressing topic of global importance, and to explore intersections between the fields of acculturation and positive youth development. From these contributions, several major challenges were identified. These included the need for greater attention to the strengths and adaptation of immigrant adolescents (i.e., to include a positive youth development framework in acculturation research and theory), the differentiation and intersections between acculturative processes and normative developmental challenges, the evolution acculturation theory, the need to better understand contact between multiple groups, the consideration of context-dependency and dynamic nature of acculturative processes. PMID- 28985960 TI - Comparison of the Pharmacokinetics of the Phase II and Phase III Capsule Formulations of Selumetinib and the Effects of Food on Exposure: Results From Two Randomized Crossover Trials in Healthy Male Subjects. AB - PURPOSE: Selumetinib (AZD6244, ARRY-142886), an oral, potent, and highly selective mitogen-activated protein kinase 1/2 inhibitor with a short half-life, has shown activity across various tumor types. Before initiation of Phase III trials, the site, scale, and color (hypromellose shell from white [Phase II] to blue [Phase III]) of the selumetinib 25mg capsule manufacture was changed. We present 2 crossover trials evaluating Phase III capsules in healthy subjects. METHODS: The relative bioavailability trial was a Phase I, open-label, randomized, 3-treatment, 4-period, 6-sequence crossover trial in healthy male subjects (aged 18-55 years). Subjects received selumetinib 75mg (3 * 25 mg) Phase II or Phase III capsules, or a 35mg oral solution, during 4 dosing periods in 1 of 6 randomized treatment sequences. The food effect trial was a Phase I, open label, randomized, 2-period crossover trial in healthy male subjects (aged 18-45 years). Subjects were randomized to 1 of 2 sequences to receive selumetinib 75mg (3 * 25 mg) Phase III capsules. In sequence 1, subjects received selumetinib after 10 hours of fasting. Following a washout period, selumetinib was administered after a high-fat meal. In sequence 2, subjects received selumetinib in the fed state, before the fasted state. Pharmacokinetic parameters were determined from serial blood sampling. FINDINGS: Twenty-seven subjects were randomized to the relative bioavailability trial; 26 completed all dosing periods. Mean selumetinib AUC was unchanged (geometric least squares mean ratio [GLSMR], 90.01% [90% CI, 81.74-99.11]). Cmax was 18% lower with the Phase III capsules (GLSMR, 81.97% [90% CI, 69.01-97.36]). A post hoc exploratory statistical analysis excluding outlying observations with later Tmax showed that Phase II and III capsules produced similar exposure in terms of Cmax and AUC. High intrasubject variability for Cmax attributed to the pharmacokinetic sampling schedule was judged to have impacted on the estimated GLSMR. In the food effect trial, 34 subjects completed both study periods. A high-fat meal reduced selumetinib Cmax compared with the fasted state (GLSMR, 49.76% [90% CI, 43.82 56.51]); AUC was minimally changed (GLSMR, 84.08% [90% CI, 80.72-87.59]). Median Tmax was prolonged by 1.49 hours. No deaths or serious adverse events were reported. IMPLICATIONS: Selumetinib 75mg (3 * 25 mg) Phase III capsules are being used in ongoing pivotal Phase III trials and should be administered in the fasted state. Based on findings from the relative bioavailability trial, pharmacokinetic sampling frequency was increased for healthy subject trials, including the food effect trial. ClinicalTrials.gov identifiers: NCT01635023 (relative bioavailability) and NCT01974349 (food effect). PMID- 28985961 TI - Volume and Patterns of Physical Activity Across the Health and Heart Failure Continuum. AB - BACKGROUND: The benefits of regular physical activity (PA) are well documented in patients with heart failure (HF), however the amount and intensity of objectively measured PA and sedentary behaviour in HF with preserved (HFPEF) or reduced ejection fraction (HFREF) is not well known. METHODS: In a cross-sectional observational study the energy expenditure of 151 participants (HFPEF: n = 53; HFREF: n = 16; at-risk for HF: n = 48; control participants: n = 34) using SenseWear Mini Armbands (Body Media, Inc, Pittsburgh, PA) were monitored. PA outcomes included time spent in different PA intensities (light and moderate vigorous PA), sedentary time, steps per day, total daily energy expenditure, PA energy expenditure, and the patterns of PA in bouts of >= 10 minutes of moderate vigorous PA. RESULTS: The patients with HFPEF had the lowest volume of activity across the 4 groups. After adjusting for covariates, only steps per day remained significantly different across groups (P = 0.0005). A comparison of HFPEF vs HFREF indicated a higher amount of time in bouts of >= 10 minutes of moderate vigorous PA for patients with HFREF (median, 2.4 [interquartile range, 0-13.5] vs 26 [3.7-46.8]; P = 0.0075). In the at-risk group, PA was lower than the recommended levels in the guidelines. CONCLUSIONS: Our findings suggest step count as the most robust outcome in evaluating daily PA in this population. Also, patients with HFPEF showed to be the least active group in the HF continuum. Monitoring volume and pattern of PA for those at risk of HF and patients with HFPEF could help to identify sedentary individuals and to develop tailored behavioural interventions for them. PMID- 28985962 TI - Coronary Vasospasm Precipitated by Pseudoephedrine, Not Metoprolol. PMID- 28985963 TI - Cerebral imaging of post-stroke plasticity and tissue repair. AB - Six months after stroke onset, 50 % of patients are still disabled and dependent, while many brain mechanisms of recovery remain partially unknown or misunderstood. However, brain imaging and cerebral connectivity analytical techniques have provided invaluable insights into such mechanisms and identified two main patterns of brain reorganization depending on stroke severity. The contralesional primary motor cortex can take over motor function in severely impaired patients, whereas the ipsilesional motor cortex or hemisphere reorganize themselves in good recoverers. These patterns evolve with time after stroke, and highlight ipsilesional and contralesional primary and secondary areas that appear to take over lost functions. The crucial role of these areas has been confirmed by histological tracer studies. In addition, non-invasive techniques can stimulate post-stroke brain plasticity, although appropriate targets first need to be found. Imaging has proved useful for finding such appropriate targets and has also provided biomarkers of efficacy with various therapies. Moreover, it has provided some clues to the mechanisms of action of recovery-enhancing drugs. These imaging techniques have also identified patients who show atypical reorganization and recovery patterns. Thus, it may be necessary to design individualized and targeted therapies. PMID- 28985964 TI - The hemoglobin derived peptide LVV-hemorphin-7 evokes behavioral effects mediated by oxytocin receptors. AB - LVV-hemorphin-7 (LVV-h7) is bioactive peptide resulting from degradation of hemoglobin beta-globin chain. LVV-h7 is a specific agonist of angiotensin IV receptor. This receptor belongs to the class of insulin-regulated aminopeptidases (IRAP), which displays oxytocinase activity. Herein, our aims were to assess whether: i) LVV-h7 modifies centrally organized behavior and cardiovascular responses to stress and ii) mechanisms underlying LVV-h7 effects involve activation of oxytocin (OT) receptors, probably as result of reduction of IRAP proteolytic activity upon OT. Adult male Wistar rats (270-370g) received (i.p.) injections of LVV-h7 (153nmol/kg), or vehicle (0.1ml). Different protocols were used: i) open field (OP) test for locomotor/exploratory activities; ii) Elevated Plus Maze (EPM) for anxiety-like behavior; iii) forced swimming test (FST) test for depression-like behavior and iv) air jet for cardiovascular reactivity to acute stress exposure. Diazepam (2mg/kg) and imipramine (15mg/kg) were used as positive control for EPM and FST, respectively. The antagonist of OT receptors (OTr), atosiban (1 and 0,1mg/kg), was used to determine the involvement of oxytocinergic paths. We found that LVV-h7: i) increased the number of entries and the time spent in open arms of the maze, an indicative of anxiolysis; ii) provoked antidepressant effect in the FS test; and iii) increased the exploration and locomotion; iv) did not change the cardiovascular reactivity and neuroendocrine responses to acute stress. Also, increases in locomotion and the antidepressant effects evoked by LVV-h7 were reverted by OTr antagonist. We conclude that LVV-h7 modulates behavior, displays antidepressant and anxiolytic effects that are mediated in part by oxytocin receptors. PMID- 28985965 TI - Ghrelin projection from the lateral hypothalamus area to the dorsal vagal complex and its regulation of gastric motility in cisplatin-treated rats. AB - OBJECTIVE: To investigate ghrelin projection from the lateral hypothalamus area (LHA) to the dorsal vagal complex (DVC) and its regulation of gastric motility in cisplatin-treated rats. MATERIALS AND METHODS: In the present study, the protein and mRNA expression of ghrelin and its receptor GHSR-1a were measured by Western blot and PCR, respectively. The ghrelin fiber projections arising from the LHA and projecting to the DVC were investigated by retrograde tracing combined with fluoro-immunohistochemical staining. The effects of ghrelin in the DVC, electrical stimulation of the LHA, and electrical lesion of the DVC on gastric motility were measured in cisplatin-treated rats. RESULTS: Ghrelin fibers originating in the LHA projected to the DVC. The protein and mRNA expression of GHSR-1a was greater in cisplatin-treated rats than in saline-treated rats. Conversely, the expression of ghrelin in the LHA and DVC was reduced in cisplatin treated rats. Cisplatin treatment also reduced gastric contractions. Ghrelin administrated into the DVC significantly promoted gastric motility, an effect completely blocked by treatment with the ghrelin receptor antagonist [D-Lys-3] GHRP-6. In addition, electrical stimulation of the LHA promoted gastric motility, though this effect was much weaker in cisplatin-treated rats than in control rats. The excitatory effect of electrical stimulation of the LHA on gastric motility was partially blocked by pretreatment of the DVC with [D-Lys-3]-GHRP-6. Electrical lesion of the DVC diminished the excitatory effect that was induced by electrical stimulation of the LHA. CONCLUSIONS: DVC, especially AP, may have a role for gastric contraction induced by the stimulation of the LHA. This regulation on gastric motility was weaker in cisplatin-treated rats than in saline-treated rats, possibly due to reduced ghrelin expression in the LHA and ghrelin projection from the LHA to the DVC. PMID- 28985966 TI - Re: 'The environmental impact of obesity: longitudinal evidence from the United States'. PMID- 28985967 TI - Re: Evaluation of compliance with the Spanish Code of self-regulation of food and drinks advertising directed at children under the age of 12 years in Spain. PMID- 28985968 TI - Should Urologists Abandon the Use of Mannitol During Partial Nephrectomy? PMID- 28985970 TI - The effects of actors vocal exercises for relaxation on fluency: A preliminary study. AB - PURPOSE: To determine the efficacy of treatment based on Kristin Linklater's technique for vocal preparation for performance for use with people who stutter. METHOD: A protocol for a treatment for stuttering involving breathing exercises, relaxation techniques, and focus on awareness was designed by the first author from Linklater's published exercises in her book Freeing the Natural Voice (2006). Four adults who stutter participated in a 12-week, single-case reversal design study. Treatment efficacy was determined by baseline and post-treatment measures on the OASES, self-report naturalness, tension and severity scale, and percentage of stuttering-like disfluency (SLD). Qualitative measures included a daily tension and practice log, a program completion questionnaire, and accounts from the clinicians administering the treatment protocol. RESULTS: Three of four participants scored lower on the OASES post-treatment, suggesting that the impact of stuttering on their daily lives had decreased. All four experienced a reduction in the number of SLD counted throughout treatment sessions compared to baseline data. CONCLUSION: A treatment for stuttering based on Linklater's work including regulation of breathing, relaxation, and awareness of breath may be effective in improving fluency and decreasing the impact of stuttering and warrants further study. PMID- 28985969 TI - Modifiable Factors Associated With Survival After Out-of-Hospital Cardiac Arrest in the Pan-Asian Resuscitation Outcomes Study. AB - STUDY OBJECTIVE: The study aims to identify modifiable factors associated with improved out-of-hospital cardiac arrest survival among communities in the Pan Asian Resuscitation Outcomes Study (PAROS) Clinical Research Network: Japan, Singapore, South Korea, Malaysia, Taiwan, Thailand, and the United Arab Emirates (Dubai). METHODS: This was a prospective, international, multicenter cohort study of out-of-hospital cardiac arrest in the Asia-Pacific. Arrests caused by trauma, patients who were not transported by emergency medical services (EMS), and pediatric out-of-hospital cardiac arrest cases (<18 years) were excluded from the analysis. Modifiable out-of-hospital factors (bystander cardiopulmonary resuscitation [CPR] and defibrillation, out-of-hospital defibrillation, advanced airway, and drug administration) were compared for all out-of-hospital cardiac arrest patients presenting to EMS and participating hospitals. The primary outcome measure was survival to hospital discharge or 30 days of hospitalization (if not discharged). We used multilevel mixed-effects logistic regression models to identify factors independently associated with out-of-hospital cardiac arrest survival, accounting for clustering within each community. RESULTS: Of 66,780 out of-hospital cardiac arrest cases reported between January 2009 and December 2012, we included 56,765 in the analysis. In the adjusted model, modifiable factors associated with improved out-of-hospital cardiac arrest outcomes included bystander CPR (odds ratio [OR] 1.43; 95% confidence interval [CI] 1.31 to 1.55), response time less than or equal to 8 minutes (OR 1.52; 95% CI 1.35 to 1.71), and out-of-hospital defibrillation (OR 2.31; 95% CI 1.96 to 2.72). Out-of-hospital advanced airway (OR 0.73; 95% CI 0.67 to 0.80) was negatively associated with out of-hospital cardiac arrest survival. CONCLUSION: In the PAROS cohort, bystander CPR, out-of-hospital defibrillation, and response time less than or equal to 8 minutes were positively associated with increased out-of-hospital cardiac arrest survival, whereas out-of-hospital advanced airway was associated with decreased out-of-hospital cardiac arrest survival. Developing EMS systems should focus on basic life support interventions in out-of-hospital cardiac arrest resuscitation. PMID- 28985971 TI - Sex differences in the end-state comfort effect in pre-adolescent children. AB - There has been recent interest in the developmental trajectory of the end-state comfort effect (ESCE) in young children. However, potential sex differences have yet to be examined in the overturned glass task. We examined the ESCE using this task in a large sample (N=232) of typically-developing elementary school children (111 girls, 121 boys) in grades 1-5 (approximately 7-11years old). We sought to determine whether there were similarities or differences in performance between boys and girls. Children picked up an overturned drinking glass from a table, turned the glass upright, and then poured water into it from a measuring cup. Three trials were performed, and the use of an initial awkward thumb-down grip to pick up the glass was taken as evidence for the ESCE. There were non-significant main effects for sex and grade, but a significant interaction between factors. Boys increased in sensitivity to end-state comfort across the five grades while girls showed a decrease from grades 1-3, followed by an increase between grades 3 and 5. Taken together, the results indicate the presence of adult-like motor planning for the overturned glass task by the 4th grade (i.e., age 10), but also suggest the presence of a motor reorganization in girls, at around the 2nd or 3rd grade (i.e., 8 or 9years of age). PMID- 28985972 TI - Quantitative methylation analysis of human papillomavirus 16L1 gene reveals potential biomarker for cervical cancer progression. AB - Human papillomavirus 16 is the most prevalent type found in cervical cancer worldwide, accounting for >50% of all cases. Quantitative methylation analysis of human papillomavirus 16L1 gene within 5' (CpGs 5600, 5606, 5609, 5615) and 3' (7136 and 7145) regions to determine potential biomarker for cervical cancer progression was performed in exfoliated cervical cells collected from 101 Thai women of precancerous and cancerous lesions. Intermediate to high methylation levels (>20%) were detected in HPV16 5'L1 regions especially CpG 5600 of all cancerous (100%) and 50% of CIN3 samples, whereas normal/CIN1 samples (80%) showed methylation levels <20%. Our results indicate the potential use of HPV 16L1 gene methylation at specific site as a biomarker for prognostic cervical cancer screening, however, suitable cutoff should be further evaluated in a larger sample size. PMID- 28985974 TI - What Is the Role of the Bacterium Propionibacterium acnes in Type 1 Modic Changes? A Review of the Literature. AB - This review presents a summary of the pathology and epidemiology of Modic changes and the possible role of Propionibacterium acnes. This information is followed by a synthesis of the most recent clinical research involved in culturing the discs of patients with degenerative disc disease for the presence of bacteria. We also discuss a randomized controlled trial that investigates the effects of antibiotics on patients with chronic low back pain and type 1 Modic changes. We conclude with a brief discussion of the difficulties involved in this research and the significance of the findings. PMID- 28985976 TI - Weight loss for the prevention and treatment of type 2 diabetes. PMID- 28985975 TI - Mental Health Screening of Medically-Admitted Patients With Cystic Fibrosis. AB - BACKGROUND: Multi-national studies have identified an increased risk for depression and anxiety among the cystic fibrosis population. People with cystic fibrosis and depression have decreased lung function, adherence, and quality of life, and increased health care utilization. This is a pilot study of mental health screening and referral of patients with cystic fibrosis in a large tertiary medical center. OBJECTIVE: Patients with a diagnosis of cystic fibrosis aged 8 and older, medically admitted to a tertiary hospital, were screened for eligibility and offered mental health screening for depression and anxiety. METHODS: Patients indicating elevated rates of anxiety, depression, or suicidal ideation were offered a psychiatric consultation, and all participants were offered mental health referrals. Health-related outcomes were gathered via medical record review. RESULTS: The pediatric population showed elevated rates/at risk of depression (17%), anxiety (22%) and clinically-elevated depression (5%), and anxiety (11%). Twenty-two percent of the youth reported suicidal ideation. The adult population reported mild rates of depression (11%), anxiety (28%), and suicidality (11%). The mental health screening process resulted in 1 mental health referral, 16 patients eligible for psychiatric consultation, and 4 completed psychiatric consultations. DISCUSSION: This study represents a pilot mental health screening in the inpatient medical setting. The results indicate an elevated rate of depression, anxiety, and suicidal ideation, and a protocol for responding to elevated responses via psychiatric consultation. This study indicates the need for further exploration of implementation of mental health screening, rapid response to suicidal ideation, referral process, and treatment interventions. PMID- 28985977 TI - Perihamate-Peripisiform-Transtriquetrum Axial Ulnar Fracture Dislocation of the Hand With an Associated Perilunate Injury. AB - Axial fracture-dislocations are rare, high-energy injuries. Although cases of axial fracture-dislocations are reported in the literature, there are few reports of a patient who suffered a combined perilunate injury with an ulnar axial dislocation of the hand. This case report describes the anatomical injury and operative treatment of a patient who suffered this injury and discusses the importance of associated soft tissue management. PMID- 28985973 TI - Treatment challenges in and outside a network setting: Soft tissue sarcomas. AB - Patients with soft tissue sarcoma (STS) experienced better outcomes when treated according to existing clinical practice guidelines either at reference institution or dedicated treatment networks. Despite increasing evidence supporting referral to sarcoma specialised units, up to half of patients are not managed according to guidelines, particularly those in the early stage of their disease requiring surgery. Also, criteria to certify expertise of institutions, such as the treatment volume, are debated and health authorities have only recently started identification of these centres and creation of treatment networks in Europe as well as in several countries. This process have important implications for both patient outcomes and innovation of existing treatment strategies through clinical research, making improvement of clinical pathways a priority for health care authorities. This article will discuss issues with management of patients with STS, such as pathological diagnosis and adherence to guidelines, and the definition of referral centres and networks will be illustrated along with existing experiences and population-based data. PMID- 28985979 TI - Feasibility of a New Pulley Repair: A Cadaver Study. AB - PURPOSE: In this study, the feasibility of a new pulley reconstruction in which the tendon graft is pulled through a tunnel in the proximal phalanx, was evaluated using a cadaver model, with particular attention paid to the weakening of the bone structure by the drill hole. METHODS: Nine fingers from 6 cadaver hands with intact pulley systems were compared with 9 fingers from 6 cadaver hands with missing A2 to A4 pulleys but that included a repair using the new surgical technique. Each finger was fixed to an isokinetic loading device. The forces in the flexor tendons were recorded in each finger using a force transducer. RESULTS: The forces recorded in the flexor tendons of the control group were significantly higher than in the reconstructed fingers. The most common event in the reconstructed fingers was graft failure. A fracture of the bone due to the drill hole was not observed. CONCLUSIONS: The new pulley reconstruction could represent an alternative to existing reconstructive techniques. The cause for the higher forces recorded in the control group could be attributed to sutures used in the operated fingers. CLINICAL RELEVANCE: The new pulley reconstruction method may enable reduced extensor tendon irritation because it avoids contact with the extensor hood and could possibly prohibit cortical bone loss, a serious side effect in the "one and one-half loop" technique. PMID- 28985978 TI - The Ethics of Hand Transplantation: A Systematic Review. AB - PURPOSE: We conducted a systematic review to document ethical concerns regarding human upper extremity (UE) allotransplantation and how these concerns have changed over time. METHODS: We performed a systematic review of 5 databases to find manuscripts addressing ethical concerns related to UE allotransplantation. Inclusion criteria were papers that were on the topic of UE allotransplantation, and related ethical concerns, written in English. We extracted and categorized ethical themes under the 4 principles of bioethics: Autonomy, Beneficence, Nonmaleficence, and Justice. We assessed theme frequency by publication year using Joinpoint regression, analyzing temporal trends, and estimating annual percent change. RESULTS: We identified 474 citations; 49 articles were included in the final analysis. Publication years were 1998 to 2015 (mean, 3 publications/y; range, 0-7 publications/y). Nonmaleficence was most often addressed (46 of 49 papers; 94%) followed by autonomy (36 of 49; 74%), beneficence (35 of 49; 71%), and justice (31 of 49; 63%). Of the 14 most common themes, only "Need for More Research/Data" (nonmaleficence) demonstrated a significant increase from 1998 to 2002. CONCLUSIONS: Upper extremity transplantation is an appealing reconstructive option for patients and physicians. Its life-enhancing (vs life-saving) nature and requirement for long term immunosuppression have generated much ethical debate. Availability of human data has influenced ethical concerns over time. Our results indicate that discussion of ethical issues in the literature increased following publication of UE transplants and outcomes as well as after meetings of national societies and policy decisions by regulatory agencies. CLINICAL RELEVANCE: Because UE transplantation is not a life-saving procedure, much ethical debate has accompanied its evolution. It is important for UE surgeons considering referring patients for evaluation to be aware of this discussion to fully educate patients and help them make informed treatment decisions. PMID- 28985980 TI - Idarucizumab Dosing in Kidney Failure. PMID- 28985981 TI - In Reply to 'Idarucizumab Dosing in Kidney Failure'. PMID- 28985982 TI - Older Suicide Decedents: Intent Disclosure, Mental and Physical Health, and Suicide Means. AB - INTRODUCTION: This study examined: (1) associations of suicide intent disclosure with depressed mood and health problems; (2) age-group differences in those associations; and (3) relationship between disclosure and suicide means among suicide decedents aged >=50 years (N=46,857). METHODS: Data came from the National Violent Death Reporting Systems, 2005-2014. Data analysis was conducted in 2017. Chi-square tests were used to compare disclosers and nondisclosers on sociodemographic and precipitating factors and suicide means. Logistic regression analyses were used to examine the research questions. RESULTS: The overall disclosure rate was 23.4%. Logistic regression results showed that both depressed mood (AOR=1.57, 95% CI=1.50, 1.65, p<0.001) and health problems (AOR=1.56, 95% CI=1.48, 1.64, p<0.001) were associated with increased odds of disclosure. Compared with decedents aged 50-59 years, those aged 70-79 years and >=80 years had greater disclosure odds. When interaction terms of age group X health problems were entered in the model, disclosure odds increased among those with health problems in the groups aged 60-69 years (ratio of AOR=1.19, 95% CI=1.06, 1.34, p=0.003), 70-79 years (ratio of AOR=1.29, 95% CI=1.13, 1.48, p<0.001), and >=80 years (ratio of AOR=1.41, 95% CI=1.20, 1.66, p<0.001). Compared with other suicide means, both firearm use and hanging/suffocation were associated with lower disclosure odds. CONCLUSIONS: The older the decedents were, the more likely they were to have disclosed suicidal intent, and health problems largely explained their higher odds of disclosure. Healthcare providers need better preparation to screen and aid those in need to prevent suicide. Social support system members should also be assisted in identifying warning signs and linking older adults to services. PMID- 28985983 TI - Medical and Surgical Management of Equine Recurrent Uveitis. AB - Equine recurrent uveitis (ERU) is characterized by recurrent bouts of inflammation interrupted by periods of quiescence that vary in duration. There is little consensus on the clinical manifestations, the underlying causes, or the management. The 3 commonly recognized syndromes of ERU (classic, insidious, and posterior) do not accurately separate the clinical manifestations of disease into distinct categories. An accurate diagnosis and early intervention are essential to minimizing the effects of disease and preserving vision. There are multiple medical and surgical options for controlling ERU as long as the disease is recognized early and targeted treatment is initiated immediately. PMID- 28985984 TI - Advanced Imaging of the Equine Eye. AB - This article reviews the literature for studies describing advanced imaging of the equine eye as a reference for practitioners to help in the selection of image modalities, describe how to use the instruments, and help interpret the image findings. Indications for, technique of, and image interpretation of advanced image modalities such as ultrasound, computed tomography, MRI, optical coherence tomography, confocal microscopy, and angiography are reviewed. The article is organized anatomically, not by instrument, so that the reader will be able to quickly research ways to image specific disease entities or anatomic locations that are affecting their equine patients. PMID- 28985985 TI - Corneal Response to Injury and Infection in the Horse. AB - This article describes the natural responses of the immune system and the cornea to injury and infection. The process of reepithelialization and reformation of stromal collagen is discussed, as are the clinical signs and manifestations of the effects of the healing response when it is routine and when it is pathologic. Excessive inflammatory or immune responses by host tissues can cause further damage that may be present from the antecedent injury or the effect of a pathogen. The clinical signs and manifestations of wound healing as well as potential therapeutic interventions are described. PMID- 28985986 TI - Sex differences in the association between perceived stress and adiposity in a nationally representative sample. AB - PURPOSE: Prior studies examining the association between perceived stress and adiposity have reported mixed findings, and sex differences have largely not been examined. METHODS: We examined the relationship between perceived stress and body mass index (BMI) and waist circumference in young adults in the National Longitudinal Study of Adolescent to Adult Health. Participants (mean age 29 years; N = 14,044) completed the short form of Cohen's Perceived Stress Scale during a home visit. Height, weight, and waist circumference were assessed during the same visit. BMI was calculated based on measured height and weight. RESULTS: In the sample, 52% were male and 65% were identified as white. In adjusted linear regression analyses, a sex by Perceived Stress Scale interaction was noted (P < .05) for both BMI and waist circumference. Perceived stress was statistically significantly associated with lower BMI (beta: -0.09; standard error [SE]: 0.05) and was associated with lower waist circumference, although not statistically significant (beta: -0.18; SE: 0.10) among men. No associations were noted among women. CONCLUSIONS: In this nationally representative sample of young adults, perceived stress was associated with lower levels of adiposity among men. Noted differences could be attributed to different behavioral and coping strategies in response to stress between men and women as well as biological mechanisms which should be explored further. PMID- 28985988 TI - A novel screwing method to prevent decubitus and skin ulcer in severe kyphoscoliosis after spinal cord injury: A case report. PMID- 28985987 TI - Kinetochore Function from the Bottom Up. AB - During a single human lifetime, nearly one quintillion chromosomes separate from their sisters and transit to their destinations in daughter cells. Unlike DNA replication, chromosome segregation has no template, and, unlike transcription, errors frequently lead to a total loss of cell viability. Rapid progress in recent years has shown how kinetochores enable faithful execution of this process by connecting chromosomal DNA to microtubules. These findings have transformed our idea of kinetochores from cytological features to immense molecular machines and now allow molecular interpretation of many long-appreciated kinetochore functions. In this review we trace kinetochore protein connectivity from chromosomal DNA to microtubules, relating new findings to important points of regulation and function. PMID- 28985989 TI - Distribution of artificial radionuclides in particle-size fractions of soil on fallout plumes of nuclear explosions. AB - In this paper are analyzed the artificial radionuclide distributions (137Cs, 90Sr, 241Am, 239+240Pu) in particle-size fractions of soils from two radioactive fallout plumes at the Semipalatinsk Test Site. These plumes were generated by a low-yield surface nuclear test and a surface non-nuclear experiment with insignificant nuclear energy release, respectively, and their lengths are approximately 3 and 0,65 km. In contrast with the great majority of similar studies performed in areas affected mainly by global fallout where adsorbing radionuclides such as Pu are mainly associated with the finest soil fractions, in this study it was observed that along both analyzed plumes the highest activity concentrations are concentrated in the coarse soil fractions. At the plume generated by the surface nuclear test, the radionuclides are concentrated mainly in the 1000-500 MUm soil fraction (enrichment factor values ranging from 1.2 to 3.8), while at the plume corresponding to the surface non-nuclear test is the 500 250 MUm soil fraction the enriched one by technogenic radionuclides (enrichment factor values ranging from 1.1 to 5.1). In addition, the activity concentration distributions among the different soil size fractions are similar for all radionuclides in both plumes. All the obtained data are in agreement with the hypothesis indicating that enrichment observed in the coarse fractions is caused by the presence of radioactive particles resulted from the indicated nuclear tests. PMID- 28985990 TI - The importance of atrial fibrillation and selected echocardiographic parameters for the effectiveness and safety of thrombolytic therapy in patients with stroke. AB - BACKGROUND: The efficacy and safety of thrombolytic therapy in stroke depend on multiple factors. The aim of this study was to evaluate the significance of atrial fibrillation the prognosis in terms of the functional status in patients with stroke treated with intravenous thrombolysis. An additional aim was also to assess the potential significance of reduced ejection fraction (EF) and enlarged left atrium (LA) of the heart for the prognosis in patients with stroke who underwent thrombolytic therapy. METHODOLOGY: A prospective study involved enrollment of 222 patients, mean age of 72 years with first-in-life ischemic stroke. In all participants there were realized procedures as follows: neurological status before administering rt-PA (NIHSS), selected echocardiographic parameters, functional status on the 14th day from the onset (mRankin scale) and analysis the bleeding events. RESULTS: Atrial fibrillation was significantly more frequent in women than men; females had higher CHA2DS2VASc scores and heavier neurological conditions on day 1 of stroke. Two independent factors for poor prognosis (3-5 points by mRankin) were found: the NIHSS score and the CHA2DS2VASc score >=3. We identified 2 independent factors for death within 14 days from the onset: the result by NIHSS and the EF. The NIHSS score turned out to be the only independent predictor of hemorrhage during hospitalization: RR 1.19; CI [1.06-1.33]; p=0.003; p for model=0.0025. CONCLUSIONS: The presence of atrial fibrillation worsens the patient's prognosis in terms of the functional status and survival during the acute period of stroke in patients treated with intravenous thrombolysis. Higher NIHSS and CHA2DS2VASc scores and reduced EF in patients with stroke treated with thrombolysis are the predictors of unfavorable short-term prognosis. PMID- 28985991 TI - Noninfectious complications of acute stroke and their impact on hospital mortality in patients admitted to a stroke unit in Warsaw from 1995 to 2015. AB - BACKGROUND: Medical complications often worsen the prognosis after stroke. Our aim was to investigate the association between particular noninfectious complications and hospital mortality of acute stroke patients admitted to an urban Polish stroke center, and changes in their occurrence from 1995 to 2015. METHODS: This is a retrospective analysis of 5174 consecutive patients admitted for acute ischemic stroke or cerebral hemorrhage to a Polish urban stroke center between 1995 and 2015. The occurrence of complications was reported for years 1995-2000 (n=883), 2001-2006 (n=1567), 2006-2010 (n=1539) and 2011-2015 (n=1183). Odds ratios (OR) with 95% confidence interval (95% CI) for stroke unit death were calculated after adjustment for age, congestive heart failure (CHF), pre-existing disability, stroke type and baseline neurological deficit in three different time periods. RESULTS: Over time there was a significant decrease in the occurrence of myocardial infarction (MI) (2.2%, 1.4%, 1.0% and 0.3%, respectively), exacerbated CHF (4.6%, 5.1%, 2.6% and 2.0%) and deep vein thrombosis (DVT) (4.6%, 2.7%, 1.2% and 1.1%). Adjusted odds for stroke unit death were increased by myocardial infarction (MI) (OR 17.5, 95% CI: 8.5-35.7), exacerbated CHF (OR 15.0, 95% CI: 9.8-23.0), pulmonary embolism (PE) (OR 11.5, 95% CI: 6.1-21.6), gastrointestinal bleeding (OR 9.2, 95% CI: 4.4-18.9) and recurrent stroke (OR 5.4, 95% CI: 3.1 9.3). CONCLUSIONS: Over the last two decades Polish urban stroke units may have achieved a significant reduction of the occurrence of some noninfectious complications (i.e. MI, exacerbated CHF and DVT). However, the list of conditions associated with stroke unit mortality includes not only MI and exacerbated CHF but also PE, gastrointestinal bleeding and recurrent stroke. PMID- 28985992 TI - Lurasidone: A New Option for Older Adults with Bipolar Disorder? PMID- 28985993 TI - Effects of engineered nanoparticles on the innate immune system. AB - Engineered nanoparticles (NPs) have broad applications in industry and nanomedicine. When NPs enter the body, interactions with the immune system are unavoidable. The innate immune system, a non-specific first line of defense against potential threats to the host, immediately interacts with introduced NPs and generates complicated immune responses. Depending on their physicochemical properties, NPs can interact with cells and proteins to stimulate or suppress the innate immune response, and similarly activate or avoid the complement system. NPs size, shape, hydrophobicity and surface modification are the main factors that influence the interactions between NPs and the innate immune system. In this review, we will focus on recent reports about the relationship between the physicochemical properties of NPs and their innate immune response, and their applications in immunotherapy. PMID- 28985994 TI - From mundane medicines to euphorigenic drugs: How pharmaceutical pleasures are initiated, foregrounded, and made durable. AB - BACKGROUND: Examining how pharmaceuticals are used to induce pleasure presents a unique opportunity for analyzing not only how pleasure is assembled and experienced through distinct consumption practices but also how mundane medicines can become euphorigenic substances. METHODS: Drawing on qualitative research on the non-medical use of prescription drugs by young adults in the United States, this paper utilizes Actor-Network Theory (ANT) to examine how prescription medicines come to produce pleasure. RESULTS: Our research found an indeterminacy of experience as individuals were initiated into prescription drug pleasures. We also found that euphorigenic effects coalesce and are foregrounded through subsequent use, and that pleasure and other forms of gratification are made durable through repeated and deliberate pharmaceutical consumption. CONCLUSION: Understanding how individuals are socialized into pharmaceutical pleasure, and how assemblages act to constitute the euphorigenic potential of pharmaceutical misuse, may allow for more context-appropriate intervention efforts. We suggest that the euphorigenic properties ascribed to prescription drugs are not inherent in their pharmaceutical formulations, but instead emerge through interactions within networks of heterogeneous actants. PMID- 28985995 TI - Aerobic granular sludge technology: Mechanisms of granulation and biotechnological applications. AB - Aerobic granular sludge (AGS) is a novel microbial community which allows simultaneous removal of carbon, nitrogen, phosphorus and other pollutants in a single sludge system. AGS is distinct from activated sludge in physical, chemical and microbiological properties and offers compact and cost-effective treatment for removing oxidized and reduced contaminants from wastewater. AGS sequencing batch reactors have shown their utility in the treatment of abattoir, live-stock, rubber, landfill leachate, dairy, brewery, textile and other effluents. AGS is extensively researched for wide-spread implementation in sewage treatment plants. However, formation of AGS takes relatively much longer time while treating low strength wastewaters like sewage. Strategies like increased volumetric flow by means of short cycles and mixing of sewage with industrial wastewaters can promote AGS formation while treating low-strength sewage. This article reviewed the state of research on AGS formation mechanisms, bioremediation capabilities and biotechnological applications of AGS technology in domestic and industrial wastewater treatment. PMID- 28985996 TI - TLR-induced secretion of novel cytokine IL-27 is defective in newly diagnosed type-2 diabetic subjects. AB - Toll-like receptors (TLRs), the innate immune receptors, act as sentinels bridging both innate and adaptive arms of immunity. In the present study, we estimated TLR-induced secretion of IL-27, IL-12, IL-23, IL-8, IP-10, IL-17, IL-6 and TNF-alpha (by ELISA) and expression of Human Leukocyte Antigen- (Human Leukocyte Antigen - antigen D Related (HLA-DR), CD69, CD80 (also known asB7-1) (by flowcytometry) and Activating Transcription Factor 3(ATF3) (by qRT-PCR) in whole blood cultures of control and type-2 diabetic (both newly diagnosed/NDD and known/KDM) subjects. TLR-induced secretion of IL-27 was significantly reduced in the NDD group compared to the control (Normal Glucose Tolerance (NGT)) and KDM groups. On the other hand, the expression of CD80 was significantly upregulated in both the monocytes and B cells in KDM group. This was associated with increased T cell activation (CD3+CD69+HLA-DR+) with increased IL-17 and reduced TNF-alpha secretion in this group. Impaired TLR-induced IL-27 secretion and augmented expression of antigen presentation molecules result in chronic T cell activation which may fuel T cell-mediated inflammation in type-2 diabetes. PMID- 28985997 TI - IL-33 gene variants and protein expression in pediatric Tunisian asthmatic patients. AB - Interleukin-33 (IL-33) is one of the last discovered members of the human IL-1 family. It is involved in the pathogenesis of many inflammatory diseases. This study investigates the relationship between IL33 gene variants and serum protein levels with the development of childhood asthma. We analyzed in this case-control study the distribution of two IL33 polymorphisms, rs7044343 and rs1342326, within 200 Tunisian children, using predefined Taqman genotyping assays. IL-33 serum levels were assessed by commercial sandwich Enzyme-linked immunosorbent assay (ELISA). The presence of rs1342326 polymorphism was significantly associated with a lower risk of asthma development. The CC [OR=0.20, CI (0.08-0.50)] and AC [OR=0.24, CI (0.11-0.49)] genotypes, as well as the C-allele [OR=0.40; CI: 0.26 0.61, P=0.00001] were associated significantly with a decreased asthma risk. However, the C-allele was more frequent in severe asthma patients than in milder ones. No association was found between rs7044343 variant and asthma. The level of IL-33 in sera was significantly increased in asthmatic children [1.48+/ 0.47pg/mL] compared to controls [0.70+/-0.18pg/mL; P<0.001]. Furthermore, this increase of IL-33 was associated with the presence of rs1342326 C allele. The IL33 rs1342326 polymorphism was associated with a lower childhood asthma risk in the Tunisian population and a higher IL-33 protein expression. PMID- 28985998 TI - Synthesis and evaluation of the inhibitory activity of the four stereoisomers of the potent and selective human gamma-glutamyl transpeptidase inhibitor GGsTop. AB - 2-Amino-4-{[3-(carboxymethyl)phenoxy](methoxy)phosphoryl}butanoic acid (GGsTop) is a potent, highly selective, nontoxic, and irreversible inhibitor of gamma glutamyl transpeptidase (GGT). GGsTop has been widely used in academic and medicinal research, and also as an active ingredient (Nahlsgen) in commercial anti-aging cosmetics. GGsTop consists of four stereoisomers due to the presence of two stereogenic centers, i.e., the alpha-carbon atom of the glutamate mimic (l/d) and the phosphorus atom (RP/SP). In this study, each stereoisomer of GGsTop was synthesized stereoselectively and their inhibitory activity against human GGT was evaluated. The l- and d-configurations of each stereoisomer were determined by a combination of a chiral pool synthesis and chiral HPLC analysis. The synthesis of the four stereoisomers of GGsTop used chiral synthetic precursors that were separated by chiral HPLC on a preparative scale. With respect to the configuration of the alpha-carbon atom of the glutamate mimic, the l-isomer (kon=174M-1s-1) was ca. 8-fold more potent than the d-isomer (kon=21.5M-1s-1). In contrast, the configuration of the phosphorus atom is critical for GGT inhibitory activity. Based on a molecular modeling approach, the absolute configuration of the phosphorus atom of the active GGsTop isomers was postulated to be SP. The SP isomers inhibited human GGT (kon=21.5-174M-1s-1), while the RP-isomers were inactive even at concentrations of 0.1mM. PMID- 28985999 TI - Discovery of renin inhibitors containing a simple aspartate binding moiety that imparts reduced P450 inhibition. AB - Discovery of potent renin inhibitors which contain a simplified alkylamino Asp binding group and exhibit improved selectivity for renin over Cyp3A4 is described. Structure-function results in this series are rationalized based on analysis of selected compounds bound to renin, and the contribution of each molecular feature leading to the reduced P450 inhibition is quantified. PMID- 28986000 TI - The effect of light-emitting diode (590/830 nm)-based low-level laser therapy on posttraumatic edema of facial bone fracture patients. AB - PURPOSE: Posttraumatic edema in facial bone fracture patients may interfere with the operation field and delay the schedule. Thus, swiftly reducing the edema alleviates patient discomfort and advances the operation date. Ice packing and compression bandages are often used for such a purpose, but such methods are often inconvenient for the face. In this study, we aim to analyze the effect of light-emitting diode (LED) (590/830 nm)-based low-level laser therapy (LLLT) in posttraumatic edema in facial bone fracture patients. MATERIALS AND METHODS: We conducted a prospective cohort study of 40 patients who were admitted to a single institution for facial bone fracture. The patients were divided into two groups of 20 each, treated either with LLLT or with sham treatment light. We used an LLLT device that consists of planar LED-based arrays with double wavelengths 590 nm and 830 nm. The patients were treated with either true or sham light from posttraumatic day 1-5, twice a day. After each treatment, the volume of a patient's face was measured with a 3-dimensional camera. We analyzed and compared the changes in facial edema. The Wilcoxon rank sum test was conducted for statistical comparison of the two groups, and significance was set to the level of p < 0.05. RESULTS: The sex ratio and mean age of the two groups were of little difference. The fracture sites included the nasal bone, orbital wall, zygomaticomaxillary bone, mandible, and frontal sinus. Mechanisms of injury included fall, assault, traffic accident, sports, and gunshot. The total operation rate of both groups was equal to 85%. Our analysis showed a 16.5% reduction of edema in the LLLT group and 7.3% in the sham light group. The edema reduction was statistically significantly greater in the LLLT group than in the sham light group (p < 0.047). CONCLUSION: LED-based LLLT is recently receiving attention worldwide for its cost-effectiveness and large coverage area compared to traditional laser therapy. Recent studies support its effectiveness in various areas such as wound healing, skin rejuvenation, and pain alleviation. In this study, we treated facial bone fracture patients with LED-based LLLT, and showed its effectiveness in reducing posttraumatic edema. PMID- 28986001 TI - A bioprosthetic total artificial heart for end-stage heart failure: Results from a pilot study. AB - BACKGROUND: The electro-hydraulically actuated Carmat total artificial heart (C TAH) is designed to replace the heart in patients with end-stage heart failure, either as bridge to transplant or destination therapy. It provides pulsatile flow and contains bio-prosthetic blood contacting materials. A clinical feasibility study was conducted to evaluate the C-TAH safety and performance. METHODS: Hospitalized patients, at imminent risk of death from irreversible biventricular failure despite optimal medical management, and not eligible for transplant or eligible but on extracorporeal life support, were enrolled. The primary endpoint was 30-days survival. RESULTS: Four patients were implanted with the C-TAH, three as destination therapy (ages 76, 68, 74) and one as bridge to transplant (age 58). They had implant times of 74, 270, 254 and 20 days respectively. All patients were free from hemolysis, clinical neurologic events, clinical evidence of thrombus and device-related infections. Hemodynamic and physical recovery allowed two patients to be discharged home for a cumulative duration of 7 months. The anticoagulation management strategy comprised initial unfractionated heparin, from postoperative day 2, followed by low molecular weight heparin and aspirin. An increased D-dimer level was observed in all patients during months 1 to 4. Temporary suspension of heparin anticoagulation resulted in thrombocytopenia and increased fibrin monomer, reversed by resuming anticoagulation with heparin. Causes of death were device-related (2 cases), respiratory failure and multi organ failure. CONCLUSIONS: Preliminary clinical results with the C-TAH demonstrated good safety and performance profiles in patients suffering from biventricular failure, which need to be confirmed in a pivotal study. PMID- 28986002 TI - Management of gastroesophageal reflux disease and hiatal hernia post-sleeve gastrectomy: cardiopexy with ligamentum teres. PMID- 28986003 TI - Postural tachycardia in hypermobile Ehlers-Danlos syndrome: A distinct subtype? AB - INTRODUCTION: It is not clear if patients with postural tachycardia syndrome (POTS) and Ehlers-Danlos syndrome (hEDS) differ from patients with POTS due to other etiologies. We compared the results of autonomic testing and healthcare utilization in POTS patients with and without hEDS. METHODS: Patients with POTS+hEDS (n=20) and POTS controls without hypermobility (n=20) were included in the study. All patients underwent autonomic testing, and the electronic medical records were reviewed to determine the number and types of medications patients were taking, as well as the number of outpatient, emergency department, and inpatient visits over the prior year. RESULTS: Patients with hEDS had twice as many outpatient visits (21 v. 10, p=0.012), were taking more prescription medications (8 vs. 5.5, p=0.030), and were more likely to see a pain physician (70% vs 25%, p=0.005). Autonomic testing demonstrated a slight reduction in heart rate variability and slightly lower blood pressures on tilt table testing in hEDS patients, however for most patients these variables remained within the range of normal. Orthostatic tachycardia on tilt table testing was greater in POTS controls (46bpm vs 39bpm, p=0.018). Abnormal QSweat responses were common in both groups (38% of POTS+hEDS and 36% of POTS controls). CONCLUSIONS: While autonomic testing results were not significantly different between groups, patients with POTS+hEDS took more medications and had greater markers of healthcare utilization, with chronic pain likely playing a prominent role. PMID- 28986004 TI - Schizophrenia in Wolfram Syndrome (DIDMOAD Syndrome): A case report in support of the mitochondrial dysfunction hypothesis. PMID- 28986005 TI - Using wearable technology to detect the autonomic signature of illness severity in schizophrenia. AB - INTRODUCTION: Research suggests that people with schizophrenia have autonomic dysfunctions. These have been linked to functioning problems, symptoms and considered a risk factor for illness chronicity. The aim of this study is to introduce a new Mobile Health (mHealth) method using wearable technology to assessing autonomic activity in people's everyday life. We aim to evaluate the new method acceptability and characterise the association between schizophrenia illness features and autonomic abnormalities. METHOD: Thirty participants with schizophrenia and 25 controls were asked to wear a mHealth device measuring autonomic activity and movements during their normal everyday life. Measures of device use acceptability were collected from all participants. Participants with schizophrenia were also assessed for symptoms and functioning levels. Measures of heart rate variability (HRV), electrodermal activity (EDA) and movement were collected by the device and groups were compared. Correlation between physiological measures, functioning, symptoms and medication levels were assessed in people with schizophrenia. RESULTS: The mHealth device method proved to be acceptable and produced reliable measures of autonomic activity and behaviour. Compared to controls, people with schizophrenia showed lower levels of HRV, movement and functioning. In people with schizophrenia illness severity, particularly positive symptoms, was associated with parasympathetic deregulation. CONCLUSIONS: Autonomic abnormalities can be detected using wearable technology from people's everyday life. These are in line with previous research and support the notion that autonomic deregulation are relevant illness features for mental and physical health in schizophrenia. This method may be developed as a monitoring system for well-being and relapse prevention. PMID- 28986007 TI - Reply to Letter to the Editor: Which clinical parameters should be used to determine systemic inflammation in cardiac surgery? PMID- 28986006 TI - Association between mismatch negativity and global functioning is specific to duration deviance in early stages of psychosis. AB - BACKGROUND: Mismatch negativity (MMN) is a candidate biomarker for early stages of psychosis. Although an association among duration MMN (dMMN), cognitive deficits, and functional outcome in chronic schizophrenia has been shown by a large-scale study, the effects of deviant type and clinical stages have not been investigated. METHODS: We investigated the relationships among dMMN, frequency MMN (fMMN), global functioning, and cognitive function in early stages of psychosis. The participants included 26 individuals with recent-onset schizophrenia (ROSZ), 30 individuals with ultra-high risk (UHR), and 20 healthy controls. RESULTS: The correlational analyses revealed that dMMN amplitude, which was impaired in the ROSZ group compared to the healthy controls, correlated with global functioning (Global Assessment of Functioning-Functioning scale) in the ROSZ (r=-0.45) and UHR (r=-0.37) groups. The amplitude of fMMN, which did not differ among the groups, correlated with working memory (r=-0.57) only in the ROSZ group. The path analyses indicated that dMMN had a direct effect on global functioning in the ROSZ and UHR groups while fMMN had a direct effect on working memory only in the ROSZ group. CONCLUSIONS: Our findings suggested that the association between MMN and global functioning was specific to the duration deviant and was already present in early stages of psychosis. These findings confirm the usefulness of dMMN as a biological marker of early psychosis to guide treatment interventions. PMID- 28986008 TI - Characterisation of the porcine eyeball as an in-vitro model for dry eye. AB - PURPOSE: To characterise the anatomical parameters of the porcine eye for potentially using it as a laboratory model of dry eye. METHODS: Anterior chamber depth and angle, corneal curvature, shortest and longest diameter, endothelial cell density, and pachymetry were measured in sixty freshly enucleated porcine eyeballs. RESULTS: Corneal steepest meridian was 7.85+/-0.32mm, corneal flattest meridian was 8.28+/-0.32mm, shortest corneal diameter was 12.69+/-0.58mm, longest corneal diameter was 14.88+/-0.66mm and central corneal ultrasonic pachymetry was 1009+/-1MUm. Anterior chamber angle was 28.83+/-4.16 degrees , anterior chamber depth was 1.77+/-0.27mm, and central corneal thickness measured using OCT was 1248+/-144MUm. Corneal endothelial cell density was 3250+/-172 cells/mm2. CONCLUSIONS: Combining different clinical techniques produced a pool of reproducible data on the porcine eye anatomy, which can be used by researchers to assess the viability of using the porcine eye as an in-vitro/ex-vivo model for dry eye. Due to the similar morphology with the human eye, porcine eyeballs may represent a useful and cost effective model to individually study important key factors in the development of dry eye, such as environmental and mechanical stresses. PMID- 28986009 TI - Cytapheresis (CAP) with leukocyte removal filter/bead column as one therapeutic option for inflammatory bowel disease. AB - Inflammatory bowel disease (IBD) like Crohn's disease and ulcerative colitis are chronic inflammatory disorders that affect the bowel. The disease is characterized by periods of clinical remission and relapse due to severe intestinal inflammation. Drug therapy of IBD is associated with unpleasant side effects. Further, efficacies of conventional drugs decrease with chronic use and this can represent a major difficulty in the long term management of IBD. However, in active IBD, leukocytes are elevated in the lesion they may be able to be a factor of IBD aggravation. Membrane filters column and leukocyte adsorbing beads have been developed which are direct blood perfusion systems for removing any desired level of leukocytes. Clinical studies with these two new models have shown good effects for active IBD. Clinical data suggest that leukocytapheresis might be an effective adjunct to therapy of IBD, to promote remission, taper conventional drug dosage and potentially should reduce the number of patients who require colectomy. The results may further understandings of the pathophysiology of IBD and this in turn should contribute to a more effective treatment of this disorder. PMID- 28986010 TI - Collaborative development of an accelerated graduate entry nursing programme outside of traditional funding mechanisms. AB - Financial support for students entering nurse education programmes has typically been the responsibility of Governments who make a substantial contribution to tuition and/or living costs. However, where programmes are not funded by Government bodies, students must make alternative arrangements for financial support. This paper explores how a university worked with local employers to design, recruit and deliver an accelerated graduate entry nursing programme and how this philosophy of collaboration ultimately led to local health employers providing sponsorship for students. Therefore, we offer for debate the benefits of collaborative curriculum design and future considerations of attracting employer funding for graduate entry nursing programmes. PMID- 28986011 TI - Trans-generational changes and rural-urban inequality in household fuel use and cookstove ventilation in China: A multi-region study of 0.5 million adults. AB - BACKGROUND: Disease burden estimates related to household air pollution (HAP) relied on cross-sectional data on cooking fuel, overlooking other important sources (e.g. heating) and temporal-regional variations of exposure in geographically diverse settings. We aimed to examine the trends and variations of for cooking and heating fuel use and ventilation in 500,000 adults recruited from 10 diverse localities of China. METHODS: At baseline (2004-08) and two subsequent resurveys (2008-14), participants of China Kadoorie Biobank, aged 30-79, reported their past and current fuel use for cooking and heating and the availability of cookstove ventilation. These were compared across regions, time periods, birth cohorts, and socio-demographic factors. RESULTS: During 1968-2014, the proportion of self-reported solid fuel use for cooking or heating decreased by two-thirds (from 84% to 27%), whereas those having complete kitchen ventilation tripled (from 19% to 66%). By 2014, despite a continuing downward trend, many in rural areas still used solid fuels for cooking (48%) and heating (72%), often without adequate ventilation (51%), in contrast to urban residents (all <5%). The large urban-rural inequalities in solid fuel use persisted across multiple generations and also varied by socioeconomic status, especially in rural areas. CONCLUSIONS: Despite marked progress in fuel modernization in the last 50 years, substantial rural-urban inequalities remain in the study population, especially those who were older or of lower socioeconomic status. Uptake of cleaner heating fuel and ventilation has been slow. More proactive and targeted strategies are needed to expedite universal access to clean energy for both cooking and heating. PMID- 28986013 TI - Is competition bad for our health(care)? We simply don't know. PMID- 28986012 TI - Effect of patient choice and hospital competition on service configuration and technology adoption within cancer surgery: a national, population-based study. AB - BACKGROUND: There is a scarcity of evidence about the role of patient choice and hospital competition policies on surgical cancer services. Previous evidence has shown that patients are prepared to bypass their nearest cancer centre to receive surgery at more distant centres that better meet their needs. In this national, population-based study we investigated the effect of patient mobility and hospital competition on service configuration and technology adoption in the National Health Service (NHS) in England, using prostate cancer surgery as a model. METHODS: We mapped all patients in England who underwent radical prostatectomy between Jan 1, 2010, and Dec 31, 2014, according to place of residence and treatment location. For each radical prostatectomy centre we analysed the effect of hospital competition (measured by use of a spatial competition index [SCI], with a score of 0 indicating weakest competition and 1 indicating strongest competition) and the effect of being an established robotic radical prostatectomy centre at the start of 2010 on net gains or losses of patients (difference between number of patients treated in a centre and number expected based on their residence), and the likelihood of closing their radical prostatectomy service. FINDINGS: Between Jan 1, 2010, and Dec 31, 2014, 19 256 patients underwent radical prostatectomy at an NHS provider in England. Of the 65 radical prostatectomy centres open at the start of the study period, 23 (35%) had a statistically significant net gain of patients during 2010-14. Ten (40%) of these 23 were established robotic centres. 37 (57%) of the 65 centres had a significant net loss of patients, of which two (5%) were established robotic centres and ten (27%) closed their radical prostatectomy service during the study period. Radical prostatectomy centres that closed were more likely to be located in areas with stronger competition (highest SCI quartile [0.87-0.92]; p=0.0081) than in areas with weaker competition. No robotic surgery centre closed irrespective of the size of net losses of patients. The number of centres performing robotic surgery increased from 12 (18%) of the 65 centres at the beginning of 2010 to 39 (71%) of 55 centres open at the end of 2014. INTERPRETATION: Competitive factors, in addition to policies advocating centralisation and the requirement to do minimum numbers of surgical procedures, have contributed to large-scale investment in equipment for robotic surgery without evidence of superior outcomes and contributed to the closure of cancer surgery units. If quality performance and outcome indicators are not available to guide patient choice, these policies could threaten health services' ability to deliver equitable and affordable cancer care. FUNDING: National Institute for Health Research. PMID- 28986014 TI - Biological cost of fosfomycin resistance in Escherichia coli in a murine model of urinary tract infection. AB - Prevalence of fosfomycin resistance in E. coli clinical isolates from UTIs remains very low. Our hypothesis was that fosfomycin resistance may be associated with a biological cost. Three groups of strains of E. coli belonging to the B2 phylogenetic group were used: clinical wild-type (WT) isolates, clinical multidrug-resistant isolates and in vitro fosfomycin-resistant derivatives from the uropathogen clinical strain E. coli CFT073. In each group fosfomycin susceptible and -resistant isolates were compared. In vitro, we found a significantly decreased growth rate for fosfomycin-resistant strains as compared with susceptible strains in the WT group. In a murine model of ascending UTI, there was a significant reduction in infection rates with fosfomycin-resistant isolates as compared with susceptible ones, in all 3 study groups, ranging from 28 to 39% (P<0.03). All fosfomycin-susceptible clinical strains were virulent in vivo (13/13), while fosfomycin-resistant clinical strains were either virulent (2/7) or non-virulent (5/7) (P<0.002). This difference was not explained by the number of virulence factors or pathogenicity-associated islands. In conclusion, fosfomycin resistance appears to carry some biological cost in E. coli, which may explain in part the apparent paradox of the low prevalence of fosfomycin resistance despite a high rate of spontaneous mutants. PMID- 28986015 TI - Mind in Deep Time: Original Participation and Re-enchantment of the World. AB - This paper describes my experiences exploring consciousness as an artist engraver, in particular the sense of reawakening the participatory primal mind, which came about through the act of engraving. This 'original participation' is viewed as a fundamental characteristic of our early Acheuelan ancestors and evidence is presented to show that they possessed both a 'modern' esthetic sense and also a prayerful, sacramental consciousness. It is suggested that this primal consciousness is a fundamental human quality that became eclipsed in the modern mind by the denial of participation and the Cartesian split between subject and object during the Scientific Revolution. It is upon this denial of participation and the illusion of objectivity that the whole methodology of natural science and the alienated outlook of contemporary culture is based. A re-enchantment of the world can take place through the re-mythologizing of consciousness and the re apprehension of original participation. PMID- 28986016 TI - Effects of Intentionally Treated Water on Growth of Arabidopsis thaliana Seeds with Cryptochrome Mutations. AB - OBJECTIVE: A previous experiment suggested that consumption of intentionally treated tea influenced subjective mood under double-blind, controlled conditions. To investigate that effect objectively, again under double-blind, controlled conditions, we studied whether Arabidopsis thaliana seeds hydrated with intentionally treated vs. untreated water would show differences in hypocotyl length, anthocyanin, and chlorophyll. DESIGN: Three Buddhist monks focused their intention on commercially bottled water with the goal of improving the growth of seeds; bottled water from the same source served as an untreated control. Seeds with the following three variations of cryptochrome (CRY) were used: the wild type Arabidopsis (Columbia-4), a gain-of-function mutation (His-CRY2), and a loss of function mutation (cry1/2), where "gain" and "loss" refer to enhanced and reduced sensitivity to blue light, respectively. Seeds were hydrated with treated or untreated water under blinded conditions, and then placed in random positions in an incubator. The germination process was repeated three times in each experiment, each time using new seeds, and then the entire experiment was repeated four times. RESULTS: Data combined across the four experiments showed a significant decrease in hypocotyl length in the His-CRY2 seedlings (treated mean 1.31 +/- 0.01mm, untreated mean 1.43 +/- 0.01mm, P < 10-13), a significant increase in anthocyanin with all three forms of cry, particularly His-CRY2 (treated mean 17.0 +/- 0.31mg, untreated mean 14.5 +/- 0.31mg, P < 10-4), and a modest increase in chlorophyll in His-CRY2 (treated mean 247.6 +/- 5.63mg, untreated mean 230.6 +/- 5.63mg, P = .05). These outcomes conformed to the monks' intentions because a decrease in hypocotyl length and increase in anthocyanin and chlorophyll are associated with enhanced photomorphogenic growth. These experiments suggest that the His-CRY2 mutation of Arabidopsis may be an especially robust "detector" of intention. PMID- 28986017 TI - Recent progress in translational cystic fibrosis research using precision medicine strategies. AB - Significant progress has been achieved in developing precision therapies for cystic fibrosis; however, highly effective treatments that target the ion channel, CFTR, are not yet available for many patients. As numerous CFTR therapeutics are currently in the clinical pipeline, reliable screening tools capable of predicting drug efficacy to support individualized treatment plans and translational research are essential. The utilization of bronchial, nasal, and rectal tissues from individual cystic fibrosis patients for drug testing using in vitro assays such as electrophysiological measurements of CFTR activity and evaluation of fluid movement in spheroid cultures, has advanced the prediction of patient-specific responses. However, for precise prediction of drug effects, in vitro models of CFTR rescue should incorporate the inflamed cystic fibrosis airway environment and mimic the complex tissue structures of airway epithelia. Furthermore, novel assays that monitor other aspects of successful CFTR rescue such as restoration of mucus characteristics, which is important for predicting mucociliary clearance, will allow for better prognoses of successful therapies in vivo. Additional cystic fibrosis treatment strategies are being intensively explored, such as development of drugs that target other ion channels, and novel technologies including pluripotent stem cells, gene therapy, and gene editing. The multiple therapeutic approaches available to treat the basic defect in cystic fibrosis combined with relevant precision medicine models provide a framework for identifying optimal and sustained treatments that will benefit all cystic fibrosis patients. PMID- 28986018 TI - Cystic Fibrosis & disorders of the large intestine: DIOS, constipation, and colorectal cancer. AB - Since 1966 when the Cystic Fibrosis Foundation Patient Registry (CFFPR) was founded, clinicians have witnessed significant advances in both the quality and quantity of life for patients living with Cystic Fibrosis (CF). As patients with CF live longer and fuller lives, increasing encumbrances from gastrointestinal manifestations of CF will be observed. This article serves to discuss "below the diaphragm" concerns involving the large intestine (Distal Intestinal Obstruction Syndrome, Constipation, and Colorectal Cancer). Avenues for development and implementation of clinical care protocols, particularly regarding proactive management of known associated conditions and cancer screening, will continue to be refined in the coming years. It falls to the multidisciplinary CF care team to be actively engaged in addressing these concerns effectively as priority shifts from relative acuity (typically related to early nutrition and lung function) to the travails of longevity as the CF population continues to age. PMID- 28986019 TI - Pancreatic insufficiency in Cystic Fibrosis. AB - Pancreatic insufficiency (PI) affects about 85% of the cystic fibrosis population. Although most are PI soon after birth, some will have pancreatic sufficiency (PS) for some or all of their life. Understanding the clinical presentation, diagnosis, and management of PI is crucial to the care of people with cystic fibrosis. PMID- 28986020 TI - Meconium ileus in Cystic Fibrosis. AB - Meconium ileus (MI) is often the first manifestation of cystic fibrosis (CF) and occurs in approximately 20% of patients diagnosed with CF. This article reviews the pathophysiology of MI and its clinical presentation. It focuses on the medical and surgical management emphasizing the importance of nutrition and a multidisciplinary approach to improve both short-term and long-term outcomes for CF patients with MI. PMID- 28986021 TI - Approach to chronic abdominal pain in Cystic Fibrosis. AB - Abdominal pain in individuals with CF is challenging for the patient as well as the physician, as the differential diagnosis can be complex. Most gastrointestinal manifestations of CF present with regional abdominal pain. Pain localization, which requires knowledge of gut development and innervation, is crucial to understanding the pathophysiology of abdominal pain in CF. The location of the pain, together with the clinical presentation, shapes the differential diagnosis and thus guides the evaluation and management. PMID- 28986022 TI - Bacterial overgrowth, dysbiosis, inflammation, and dysmotility in the Cystic Fibrosis intestine. AB - Gastrointestinal disease in Cystic Fibrosis (CF) is caused by defective chloride and bicarbonate transport in intestinal cells leading to reduced intraluminal fluidity, increased mucous viscosity and consequently development of intestinal inflammation, dysbiosis and often times dysmotility. This triad is also referred to as the "CF gut". A diagnosis is mainly based on clinical observation and treatment is often times decided empirically. This review of the literature should provide CF caregivers with some tools to identify intestinal inflammation, dysbiosis and dysmotility as possible cause for their patient's gastrointestinal complaints and provide an overview of our current approach to its management. PMID- 28986023 TI - Gallbladder and bile duct disease in Cystic Fibrosis. AB - Cystic fibrosis (CF) is a multi-organ, clinically diverse disorder caused by mutations in the cystic fibrosis transmembrane conductance receptor (CFTR). Awareness of extra-pulmonary manifestations, including gastrointestinal and hepatobiliary disturbances, is an increasingly important part of providing high quality care to patients with CF. Furthermore, biliary disorders, including gallbladder and bile duct disease, are common complications of CF. Therefore, a thorough understanding and efficient clinical evaluation of the gallbladder and biliary tree is an important aspect of integrated care for the patient with CF in order to prevent progression of undetected pathology. This best practice article summarizes the basis for gallbladder and bile duct pathology, describes the context and clinical presentation of biliary disease, and provides recommended approaches to delivery of high-quality care for patients with CF. PMID- 28986024 TI - Cystic Fibrosis and gastroesophageal reflux disease. AB - Gastroesophageal reflux is common in children and adults with cystic fibrosis (CF). Pathological gastroesophageal reflux disease (GERD) is also frequent in patients of all ages with CF. This article reviews the pathophysiology, diagnostic work-up, management options, complications, and future directions in the evaluation and management of GERD - unique to and pertinent for - patients with CF in particular. PMID- 28986025 TI - Introduction. PMID- 28986026 TI - Nutrition: Prevention and management of nutritional failure in Cystic Fibrosis. AB - Close monitoring of nutritional status is critical to the overall health of a patient with CF. As part of routine CF care, measurement of weight and height (and calculation of weight/length or BMI as appropriate) should be performed and analyzed at each visit. Early recognition of nutritional risk is imperative and evaluation with a multidisciplinary team should be performed to assess for caloric intake, caloric malabsorption, and other causes of poor weight gain and growth. Many tools are available to use for intervention, including oral supplementation, behavioral interventions, medications, nutritional therapies, and enteral tube feeding. PMID- 28986027 TI - Cystic Fibrosis-related cirrhosis. AB - While liver involvement is common in cystic fibrosis, the major liver disorder with impact on the clinical outcome of individuals with CF is the development of multilobular cirrhosis with progression to portal hypertension. Interestingly, this is a disorder primarily of children and adolescents. We review the proposed pathogenesis, clinical presentation, diagnostic work-up, medical and surgical management, and complications of CF cirrhosis. PMID- 28986028 TI - Pancreatitis and pancreatic cystosis in Cystic Fibrosis. AB - The pathologic effects of an altered cystic fibrosis transmembrane receptor (CFTR) protein on the exocrine pancreas is ubiquitous and of varying severity. In this section, pancreatitis and pancreatic cystosis are covered. PMID- 28986030 TI - Working towards HIV prevention choices for women. PMID- 28986029 TI - Daily and non-daily pre-exposure prophylaxis in African women (HPTN 067/ADAPT Cape Town Trial): a randomised, open-label, phase 2 trial. AB - BACKGROUND: The relative feasibility and acceptability of daily versus non-daily dosing of oral HIV pre-exposure prophylaxis (PrEP) among women are unknown. We aimed to investigate the feasibility of non-daily PrEP regimens in adult women. METHODS: We did a randomised, open-label, phase 2 clinical trial (HPTN 067/ADAPT) of oral PrEP with emtricitabine plus tenofovir disoproxil fumarate at a research centre in Cape Town, South Africa. Participants were adult women (age >=18 years) who received directly observed dosing once a week for 5 weeks followed by random assignment (1:1:1) at week 6 to one of three unblinded PrEP regimens for self administered dosing over 24 weeks: daily; time-driven (twice a week plus a post sex dose); or event-driven (one tablet both before and after sex). Primary outcomes were PrEP coverage (at least one dose within the 4 days before sex and one dose within 24 h after sex), pills needed or used to achieve regimen-specific adherence and coverage, and symptoms and side-effects. All analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01327651; the trial is completed and this report presents the final analysis. FINDINGS: Between Sept 12, 2011, and Oct 3, 2012, 191 women were enrolled to the trial. 178 (93%) completed directly observed dosing and were randomly assigned one of the three PrEP regimens for the self-administered phase: 59 were allocated the daily regimen, 59 the time-driven regimen, and 60 the event-driven regimen. Median age of women was 26 years (IQR 21-37; range 18-52). In women allocated the daily regimen, 1459 (75%) of 1952 sex events were covered by PrEP, compared with 599 (56%) of 1074 sex events among those assigned the time-driven regimen (odds ratio [OR] 2.35, 95% CI 1.43-3.83; p=0.0007) and 798 (52%) of 1542 sex events among those allotted the event-driven regimen (2.76, 1.68-4.53; p<0.0001). Fewer pills were needed for complete adherence in women allocated non-daily regimens (vs daily regimen, relative mean 2.53 [95% CI 2.39-2.69] for the time-driven regimen and 4.16 [3.59-4.82] for the event-driven regimen; p<0.0001). Side effects were uncommon. Eight HIV seroconversions occurred overall, with four documented during the self-administered phase (two with the time-driven regimen and two with the event-driven regimen). Adherence to the assigned regimen was 75% (7283 of 9652 doses taken) for women allocated the daily regimen compared with 65% for those assigned the time-driven regimen (2367 of 3616 doses taken; p=0.0028) and 53% for those allotted the event-driven regimen (1161 of 2203 doses taken; p<0.0001). When sex was reported in the previous week, PrEP drugs were detected (above the lower limits of quantification) more frequently in women assigned the daily regimen (73 [68%] of 107 samples) than in those allocated the time-driven regimen (42 [58%] of 72 samples) and the event-driven regimen (41 [41%] of 99 samples). INTERPRETATION: Daily PrEP dosing resulted in higher coverage of sex events, increased adherence to the regimen, and augmented drug concentrations than did either time-driven or event-driven dosing. These findings support recommendations for daily use of PrEP with oral emtricitabine plus tenofovir disoproxil fumarate in women. FUNDING: HIV Prevention Trials Network. PMID- 28986031 TI - Cardiovascular risk prediction model for Omanis with type 2 diabetes. AB - AIM: To date, no cardiovascular risk assessment tool has been developed specifically for any Arabian population including Omanis. This study aims to develop a suitable cardiovascular risk prediction model in the form of a statistical equation, for Omanis with type 2 diabetes. MATERIALS AND METHODS: A sample of 2039 patients with type 2 diabetes selected from primary care settings in the Aldakhiliyah Province of Oman were involved in a retrospective cohort study. All patients were free of cardiovascular disease at baseline (in 2009 2010) and were followed up until: 1) their first cardiovascular event occurred; 2) the patient died, or 3) the end of the data collection in December 2015. RESULTS: Among the total sample, 192 cardiovascular disease events were recorded within a mean follow-up period of 5.3-year. The 5-year probability of a cardiovascular event was given as 1-0.9991Exp?XiBi, where Exp ?XiBi (hazard ratio)=Exp (0.038 age+0.052 DM duration+0.102 HbA1c+0.201 total cholesterol+0.912 albuminuria [1 if present]+0.166 hypertension [1 if present]+0.005 BMI). CONCLUSION: The first cardiovascular risk prediction tool in the Arab world was developed in this study. It may be used to estimate the 5-year cardiovascular risk among Omanis with type 2 diabetes in order to plan patient management and preventive measures. However, further validation studies are required to determine the accuracy of the model. PMID- 28986033 TI - Splicing factor mutations in the myelodysplastic syndromes: target genes and therapeutic approaches. AB - Mutations in splicing factor genes (SF3B1, SRSF2, U2AF1 and ZRSR2) are frequently found in patients with myelodysplastic syndromes (MDS), suggesting that aberrant spliceosome function plays a key role in the pathogenesis of MDS. Splicing factor mutations have been shown to result in aberrant splicing of many downstream target genes. Recent functional studies have begun to characterize the splicing dysfunction in MDS, identifying some key aberrantly spliced genes that are implicated in disease pathophysiology. These findings have led to the development of therapeutic strategies using splicing-modulating agents and rapid progress is being made in this field. Splicing inhibitors are promising agents that exploit the preferential sensitivity of splicing factor-mutant cells to these compounds. Here, we review the known target genes associated with splicing factor mutations in MDS, and discuss the potential of splicing-modulating therapies for these disorders. PMID- 28986032 TI - Phosphatidic acid-producing enzymes regulating the synaptic vesicle cycle: Role for PLD? AB - In cortical and hippocampal neurons of the mammalian brain, the synaptic vesicle cycle is a series of steps that tightly regulate exo- and endocytosis of vesicles. Many proteins contribute to this regulation, but lipids have recently emerged as critical regulators as well. Of all the many lipid signaling molecules, phosphatidic acid is important to the physical processes of membrane fusion. Therefore, the lipid-metabolizing enzymes that produce phosphatidic acid are vital to the regulation of the cycle. Our lab is particularly interested in the potential regulatory mechanisms and neuronal roles of two phosphatidic acid producing enzymes: diacylglycerol kinase theta (DGKtheta) and phospholipase D (PLD). We recently discovered a regulatory role of DGKtheta on evoked endocytosis (Goldschmidt et al., 2016). In addition to this enzyme, studies implicate PLD1 in neurotransmission, although its precise role is of some debate. Altogether, the production of phosphatidic acid by these enzymes offer an interesting and novel pathway for the regulation of the synaptic vesicle cycle. PMID- 28986034 TI - Update on the epidemiology of rotavirus in the Middle East and North Africa. AB - Rotavirus (RV) is the leading cause of severe acute gastroenteritis (AGE) worldwide. Consequently, we conducted a systematic literature review on articles studying RV in the 25 countries of the MENA region during the past 15years (2000 2015). The methods and reporting were set according to the 2015 preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) and based on the elements from the international prospective register of systematic reviews (PROSPERO). Our literature search identified 169 studies meeting our predefined inclusion criteria. Studies reporting on RV were conducted in 19 out of the 24 countries of the MENA region. The largest number of studies was reported in Turkey (n=32), Iran (n=31), Saudi Arabia (n=19) and Egypt (n=17). The majority of studies reporting on RV gastroenteritis rates were clinical observational studies. In 115 studies out of 169, RV was reported among in patients whereas 35 studies reported RV among outpatients. The predominantly reported RV genotype in the region was G1[P8] followed by G2[P4] and G9[P8]. The majority of studies (n=108) were conducted among children less than 5years of age whereas the remaining studies reported on AGE among other age groups and rarely adults. In MENA countries, RV infection was reported all year round with peaks described in cold as well as hot months. This systematic review provides a current update on the epidemiology of RV-associated gastroenteritis in countries of the MENA region and draws attention to the major gaps existing in the continuous monitoring of RV. PMID- 28986035 TI - Estimating the full public health value of vaccination. AB - There is an enhanced focus on considering the full public health value (FPHV) of vaccination when setting priorities, making regulatory decisions and establishing implementation policy for public health activities. Historically, a therapeutic paradigm has been applied to the evaluation of prophylactic vaccines and focuses on an individual benefit-risk assessment in prospective and individually randomized phase III trials to assess safety and efficacy against etiologically confirmed clinical outcomes. By contrast, a public health paradigm considers the population impact and encompasses measures of community benefits against a range of outcomes. For example, measurement of the FPHV of vaccination may incorporate health inequity, social and political disruption, disruption of household integrity, school absenteeism and work loss, health care utilization, long term/on-going disability, the development of antibiotic resistance, and a range of non-etiologically and etiologically defined clinical outcomes. Following an initial conference at the Fondation Merieux in mid-2015, a second conference (December 2016) was held to further describe the efficacy of using the FPHV of vaccination on a variety of prophylactic vaccines. The wider scope of vaccine benefits, improvement in risk assessment, and the need for partnership and coalition building across interventions has also been discussed during the 2014 and 2016 Global Vaccine and Immunization Research Forums and the 2016 Geneva Health Forum, as well as in numerous publications including a special issue of Health Affairs in February 2016. The December 2016 expert panel concluded that while progress has been made, additional efforts will be necessary to have a more fully formulated assessment of the FPHV of vaccines included into the evidence base for the value proposition and analysis of unmet medical need to prioritize vaccine development, vaccine licensure, implementation policies and financing decisions. The desired outcomes of these efforts to establish an alternative framework for vaccine evaluation are a more robust vaccine pipeline, improved appreciation of vaccine value and hence of its relative affordability, and greater public access and acceptance of vaccines. PMID- 28986037 TI - A Practical Approach to the Management of Micronutrients and Other Nutrients of Concern in Food Exchange Lists for Meal Planning. PMID- 28986036 TI - Association between Haemagglutination inhibiting antibodies and protection against clade 6B viruses in 2013 and 2015. AB - BACKGROUND: The epidemiology of the pandemic A(H1N1) virus has been changing as population immunity continues to co-evolve with the virus. The impact of genetic changes in the virus on human's susceptibility is an outstanding important question in vaccine design. In a community-based study, we aim to (1) determine the genetic characteristics of 2009-2015 pandemic H1N1 viruses, (2) assess antibody response following natural infections and (3) assess the correlation of A/California/07/09 antibody titers to protection in the 2013 and 2015 epidemics. METHODS: In a household transmission study, serum specimens from 253 individuals in Managua, Nicaragua were analyzed. Combined nose and throat swabs were collected to detect RT-PCR confirmed influenza infection and virus sequencing. Hemagglutination inhibition assays were performed and the protective titer for circulating H1N1pdm was determined. RESULTS: Clade 6B pandemic H1N1 viruses predominated in Nicaragua during the 2013 and 2015 seasons. Our household transmission study detected a household secondary attack rate of 17% in 2013 and 33% in 2015. Infected individuals, including vaccinees, showed an apparent antibody response to A/California/07/09. Baseline titers of A/California/07/09 antibodies were found to associate with protection in both seasons. A titer of >=1:40 correlated to a 44% protection in children, a 29% protection in adults 15 49years old and a 51% protection in adults 50-85years old. CONCLUSION: In 2013 and 2015, antibody titers to A/California/07/09 associated with an infection risk reduction amongst exposed household contacts. This is consistent with a detectable vaccine effectiveness reported in a number of studies. Genetic changes in clade 6B viruses might have led to a reduced immunity in some whereas others might have been less affected. The use of human serologic data is important in virus characterization and if performed in a timely manner, could assist in vaccine strain selection. PMID- 28986038 TI - Reconstruction of the anterior chest wall with a 3-dimensionally printed biodynamic prosthesis. PMID- 28986039 TI - Reoperation rate for recurrent mitral disease is low after robotically assisted mitral valve repair. PMID- 28986040 TI - Segmentectomy of the left superior segment (S6) 4 years after segmentectomy of the left dorsobasal segment (S10). PMID- 28986042 TI - Open reoperations for complications of endovascular aortic procedures: Tip of the iceberg? PMID- 28986041 TI - Improvement in TNM staging of pulmonary neuroendocrine tumors requires histology and regrouping of tumor size. AB - OBJECTIVE: Neuroendocrine tumors of the lung are currently staged with the 7th edition TNM non-small cell lung cancer staging system. This decision, based on data analysis without data on histology or disease-specific survival, makes its applicability limited. This study proposes a specific staging system for these tumors. METHODS: We retrospectively analyzed 510 consecutive patients (female/male, 313/197; median age, 61 years; interquartile range, 51-70) undergoing lung resection for a primary neuroendocrine tumor between 2000 and 2015 in 8 centers. Multivariable analysis was performed using a Cox proportional hazard model to identify factors associated with disease-specific survival. A new staging system was proposed on the basis of the results of this analysis. Kaplan Meier disease-specific survival was analyzed by stage using the proposed and the 7th TNM staging system. RESULTS: Follow-up was completed in 490 of 510 patients at a median of 51 months (interquartile range, 18-99). Histology (G1-typical carcinoid vs G2-atypical carcinoid vs G3-large-cell neuroendocrine carcinoma) and pT were independently associated with survival, but pN was not. After regrouping histology and pT, we proposed the following staging system: IA (pT1-2G1), IB (pT3G1, pT1G2), IIA (pT4G1, pT2-3G2, pT1G3), IIB (pT4G2, pT2-3G3), and III (pT4G3). The 5-year survivals were 97.9%, 81.0%, 69.1%, 51.8%, and 0%, respectively. By using the 7th TNM, 5-year survivals were 95.0%, 92.3%, 67.7%, 70.9%, and 65.1% for stage IA, IB, IIA, IIB, and III, respectively. CONCLUSIONS: Incorporating histology and regrouping tumor stage create a unique neuroendocrine tumor staging system that seems to predict survival better than the 7th TNM classification. PMID- 28986043 TI - Yet another risk factor appears. PMID- 28986044 TI - Mitral repair failures are not the robot's fault! PMID- 28986045 TI - Is acetaminophen safe in pregnancy? AB - Acetaminophen is thought to be the safest analgesic and antipyretic medicine for pregnant women, and it is widely used all over the world. However, prenatal acetaminophen was reported to be associated with asthma, lower performance intelligence quotient (IQ), shorter male infant anogenital distance (predicting poor male reproductive potential), autism spectrum disorder, neurodevelopmental problems (gross motor development, communication), attention deficit/hyperactivity disorder, poorer attention and executive function, and behavioral problems in childhood. Each article has poor power to show risks of acetaminophen, however, the integration of the articles that showed adverse effects of acetaminophen may have power to show them. Acetaminophen use in childhood was associated with autism spectrum disorder, asthma symptoms, wheezing, and allergic disease. Acetaminophen is the safest medicine as analgesics for nociceptive pain and antipyretics in childhood and pregnancy. There is no alternative medication of acetaminophen. Acetaminophen should not be withheld from children or pregnant women for fears it might develop adverse effects. Acetaminophen should be used at the lowest effective dosage and for the shortest time. When we know the possible, rare but serious complications, we should use acetaminophen in pregnancy only when needed and no safer option for pain or fever relief is available. Health care providers should help inform the general lay public about this difficult dilemma. PMID- 28986046 TI - Reply to the letter of Robert L. Folmer: Does treatment response depend on the type of stimulation device? PMID- 28986047 TI - Factors that contribute to the efficacy of repetitive transcranial magnetic stimulation (rTMS) for tinnitus treatment. PMID- 28986048 TI - Open reduction-internal fixation versus intramedullary nailing for humeral shaft fractures: an expected value decision analysis. AB - BACKGROUND: Previous randomized controlled studies and meta-analyses have failed to collectively favor either open reduction-internal fixation (ORIF) or intramedullary nailing (IMN) fixation. The purpose of our investigation was to elucidate the optimal decision between ORIF and IMN for acute traumatic operative humeral shaft fractures through an expected value decision analysis. METHODS: We performed an expected value decision analysis and sensitivity analysis to elucidate the difference between ORIF and IMN fixation for patients with acute traumatic humeral shaft fractures. We surveyed 100 consecutive, randomly selected volunteers for their outcome preferences. Outcomes included union, delayed union, major complications, minor complications, and infection. A literature review was used to establish probabilities for each of these respective outcomes. A decision tree was constructed and a fold-back analysis was performed to find an expected patient value for each treatment option. RESULTS: The overall patient expected values for ORIF and IMN were 12.7 and 11.2, respectively. Despite artificially decreasing the rates of major complications, infection, delayed union, and nonunion each to 0% for IMN fixation (sensitivity analysis), ORIF continued to maintain a greater overall patient expected value (12.7 vs. 11.4, 11.2, 11.2, and 12.1, respectively). Only if the rate of nonunion after ORIF was increased from 6.1% to 16.8% did the overall expected outcome after ORIF equal that of IMN (11.2). CONCLUSION: Our expected value decision analysis demonstrates that patients favor ORIF over IMN as the optimal treatment decision for an acute traumatic humeral shaft fracture. PMID- 28986049 TI - Correction to Lancet Glob Health 2017; 5: e545-55. PMID- 28986050 TI - Correction to Lancet Glob Health 2017; 5: e984-91. PMID- 28986051 TI - Effect of intermediate dose dexamethasone on post-operative pain in lumbar spine surgery: A randomized, triple-blind, placebo-controlled trial. AB - OBJECTIVES: Dexamethasone has demonstrated analgesic properties and is used as an adjunctive pain agent for many procedures. We evaluated the efficacy of a single, intermediate dose of dexamethasone on post-operative analgesic consumption, and pain scores for lumbar spine surgery. METHODS: Eighty patients aged between 18 and 70 scheduled for lumbar decompressive laminectomy were randomly allocated into two groups to receive either intravenous 0.2 mg/kg dexamethasone (group D = 40) or normal saline (group P = 40) before anesthetic induction. Post-operative total morphine consumption and the respective pain score at the PACU, 4, 6, 12, 24 and 48 h were evaluated. In addition, any adverse events were recorded. RESULTS: Total post-operative morphine consumption within 48 h was significantly lower in group D (34.5 vs. 42.5 mg, p = 0.031); however, the respective morphine consumption at each assessment was similar between groups. The respective NRS pain score at rest and upon movement in both groups was not significantly different for any time comparison. The average NRS pain score at rest and upon movement within 48 h was similar in both groups (i.e., NRS at rest Group D 3.6 vs. Group P 3.8, p = 0.936, and NRS for movement Group D 6.2 vs. Group P 6.3, p = 0.791). The adverse events within 48 h were also similar and serious complications (i.e., respiratory depression or surgical infection) were not found in either group. CONCLUSION: A single, intermediate dose of dexamethasone before anesthetic induction could minimally decrease post-operative morphine consumption within 48 h after lumbar decompressive laminectomy without any effect on the pain score. PMID- 28986052 TI - An effective algorithm for the serological diagnosis of idiopathic inflammatory myopathies: The key role of anti-Ro52 antibodies. AB - BACKGROUND: Patients with suspected idiopathic inflammatory myopathies (IIM) are commonly tested for the presence of anti-nuclear antibodies (ANA) by indirect immunofluorescence (IIF) on HEp-2 cell substrates. However, ANA-IIF false negative tests may occur in IIM because some antigens, such as Jo1 and Ro52, may be scarcely expressed on HEp-2 cells. In addition, cytoplasmic staining is often not appropriately investigated by a specific antibody assay, leading to decreased clinical sensitivity of the ANA test. We evaluated the diagnostic impact of different strategies using different combination of myositis-related autoantibody tests. METHODS: Sera from 51 patients with an established diagnosis of IIM were tested for ANA by IIF on HEp-2 cells and for myositis-specific antibodies (MSA) and myositis-associated antibodies (MAA) by lineblot methods. RESULTS: Forty four/51 (86.3%) samples tested positive with at least one of the three methods and seven were negative with all methods. Of the 44 positive samples, 9 (20.5%) tested negative for the ANA-IIF test and positive for MAA/MSA. Anti-Ro52 were the most prevalent autoantibodies in IIM patients (21/51; 41%), frequently associated with anti-Jo1 antibodies (13/21; 62%). 13 (16%) anti-Ro52 and anti-Jo1 negative samples were reactive to MSA. CONCLUSIONS: Our findings suggest that when IIM is clinically suspected, the optimal diagnostic algorithm is to associate the ANA IIF screening test with a specific test for anti-Ro52 and anti-Jo1 antibodies. Should all these tests be negative, serological tests for MSA are recommended. PMID- 28986053 TI - External quality assessment program on urinary dysmorphic erythrocytes. PMID- 28986054 TI - Reduced aggrecan expression affects cardiac outflow tract development in zebrafish and is associated with bicuspid aortic valve disease in humans. AB - Hemodynamic forces have been known for a long time to regulate cardiogenic processes such as cardiac valve development. During embryonic development in vertebrates, the outflow tract (OFT) adjacent to the ventricle comes under increasing hemodynamic load as cardiogenesis proceeds. Consequently, extracellular matrix components are produced in this region as the cardiac cushions form which will eventually give rise to the aortic valves. The proteoglycan AGGRECAN is a key component of the aortic valves and is frequently found to be deregulated in a variety of aortic valve diseases. Here we demonstrate that aggrecan expression in the OFT of developing zebrafish embryos is hemodynamically dependent, a process presumably mediated by mechanosensitive channels. Furthermore, knockdown or knockout of aggrecan leads to failure of the OFT to develop resulting in stenosis. Based on these findings we analysed the expression of AGGRECAN in human bicuspid aortic valves (BAV). We found that in type 0 BAV there was a significant reduction in the expression of AGGRECAN. Our data indicate that aggrecan is required for OFT development and when its expression is reduced this is associated with BAV in humans. PMID- 28986055 TI - Gender differences in the association of epicardial adipose tissue and coronary artery calcification: EPICHEART study: EAT and coronary calcification by gender. AB - BACKGROUND: The association of epicardial adipose tissue (EAT) and coronary artery calcification (CAC) seems to differ by gender. However, few studies have controlled for body size, and the ideal method for body size indexing has not been explored. OBJECTIVES: To analyse the effect of gender related-body size and body fat differences on the association of EAT with CAC. METHODS: This was a prospective cohort of 371 severe aortic stenosis patients (77+/-8.5year-old, 51% females) referred to cardiac surgery. Agatston calcium score, EAT volume and visceral abdominal fat (VAF) were obtained by computed tomography. Body composition was determined using bioelectrical impedance analysis. Body weight and height were measured to derive body mass index (BMI), body surface area (BSA), and body surface index (BSI). EAT volume was normalized for BSA, weight and height. RESULTS: Median CAC score was higher in men (887; IQR: 2010) than in women (279: IQR: 145) (p<0.01). Similarly, men had higher volume of EAT than women (137+/-65.6 vs. 106+/-65.6mL, p<0.01), even when BSA- or height-indexed, but not if weight-indexed. EAT volume was associated with CAC adjusting for adiposity (BMI or BSI and VAF, or fat mass), but not with further adjustment for gender. In a stratified analysis, absolute- and indexed-volumes of EAT were independently associated with CAC in men while no association was found in women (gender-interaction p<0.05). CONCLUSIONS: In these high-risk patients, we demonstrated that EAT was associated with CAC score irrespective of body size, body fat and cardiovascular risk factors in men but not in women. PMID- 28986056 TI - Fibrinogen levels compensation of thrombocytopenia-induced bleeding following cardiac surgery. AB - BACKGROUND: After cardiopulmonary bypass (CPB) thrombocytopenia is a relatively common pattern which may trigger postoperative bleeding. The purpose of this study is to verify if the endogenous fibrinogen levels are independent determinants of chest drain blood loss and need for allogeneic blood products transfusions in a clinical model of post-CPB thrombocytopenia. METHODS: Retrospective analysis on 445 consecutive patients having a platelet count <100*1000cells/MUL after CPB. Based on the fibrinogen levels the patients were divided into three groups with similar platelet count and low (LF, median 170mg/dL), intermediate (IF, median 215mg/dL), and high (HF, median 280mg/dL), fibrinogen levels. Chest drain blood loss (mL/12h), transfusion rate of red blood cells (RBC), fresh frozen plasma (FFP) and platelet concentrates were assessed and compared between groups. RESULTS: There was a significant (P=0.001) difference in chest drain blood loss with higher values in the LF group (487mL/12h, IQR 300-600mL/12h) than in the IF group (350mL/12h, IQR 200 500mL/12h) and the HF group (300mL/12h, IQR 200-475mL/12h). Transfusion rates of FFP significantly (P=0.014) differed between groups (LF: 18.4%, IF: 7.9%, HF: 9.2%) and platelet concentrate transfusions significantly (P=0.020) differed between groups (LF: 23.5%, IF: 16.5%, HF: 10.7%). In multivariable models, these differences were confirmed. Thromboelastography parameters showed an effective compensation of clot firmness in group HF vs. IF and LF. CONCLUSIONS: Levels of fibrinogen >240mg/dL compensate the decrease in clot firmness observed in thrombocytopenic patients following CPB, and reduce bleeding and transfusion needs. PMID- 28986057 TI - Myeloid-related protein-8/14 in acute coronary syndrome. AB - BACKGROUND: The alarmin family member myeloid-related protein (MRP)-14 (S100A9), which has been identified by platelet transcriptional profiling as an acute myocardial infarction gene, regulates vascular inflammation and thrombosis. Elevated plasma levels of MRP-8/14 (S100A8/A9) heterodimer predict first and recurrent cardiovascular events. The aim of this study was to elucidate pathophysiological roles of MRP-8/14 in acute coronary syndrome (ACS). METHODS AND RESULTS: In 38 consecutive ACS patients, the MRP-8/14 level in coronary artery blood obtained at thrombus aspiration was higher in 23 patients, in whom aspirated thrombus was confirmed, compared to the 15 patients, in whom it was absent [4.86 (1.95, 8.29) vs 2.94 (1.31, 4.44), P=0.017]. The MRP-8/14 level was correlated with myeloperoxidase (MPO) level (R2=0.52), but not with soluble P selectin level (R2=0.0002) in the coronary artery blood. Immunohistochemistry of the aspirated thrombus exhibited that expression of MRP8/14 was co-localized with leukocytes positive for activated Mac-1. Finally, in cultured human umbilical vein endothelial cells, MRP-8/14 increased tissue factor expression. CONCLUSIONS: Our findings indicate that MRP-8/14 concentration increases in coronary artery blood in association with thrombus formation in ACS, co-localizes with leukocytes, and is associated with leukocyte activation. MRP-8/14 is positioned as a unique biomarker at the interface of inflammation and thrombosis in ACS. PMID- 28986058 TI - Impact of switching to polypill based therapy by baseline potency of medication: Post-hoc analysis of the SPACE Collaboration dataset. AB - BACKGROUND: Fixed dose combinations of cardiovascular therapy ('polypills') have now been launched in several dozen countries. There is considerable clinical interest in the effects of switching to polypill-based care from typical current treatment regimens, especially if polypills contain components at sub-maximal dosage. METHODS: The SPACE Collaboration includes three trials of polypill based care vs usual care in patients with established CVD or at high calculated risk. Individual patient data for 3140 trial participants were combined. Patients were categorized according to the potency of the statin and the number of BP lowering medications they were taking at baseline. Effects on adherence to anti-platelet medication, systolic blood pressure (SBP) and LDL cholesterol stratified by baseline potency of medication were determined using fixed effects models. RESULTS: Randomisation to the polypill group was associated with improved SBP at 12months, but this improvement varied according to baseline BP regimen: -3.3, 5.9, -2.5 and +1mmHg for patients taking 0, 1, 2 and 3+ BP lowering medications at baseline. For changes in LDL cholesterol at 12months, significant improvements in LDL cholesterol were seen for those taking no statin (-0.21mmol/L; 95% CI: 0.34 to -0.07), less potent statin (-0.16mmol/L; 95% CI: -0.29 to -0.04) and equipotent statins (-0.14mmol/L; 95% CI -0.26 to -0.02) at baseline. CONCLUSION: The adherence benefits of polypills tend to offset the loss of potency from use of individual components with lower dose potency, and to facilitate improvements in multiple risk factors. PMID- 28986059 TI - The day of the week and acute heart failure admissions: Relationship with acute myocardial infarction, 30-day readmission rate and in-hospital mortality. AB - BACKGROUND: In-hospital care may be constrained during the weekend due to lesser resources. Impact on outcomes of weekend versus weekday care in congestive heart failure (HF) needs further study. METHODS: Admissions with a primary diagnosis of HF using ICD-9CM codes were studied. 22,287 HF-admissions from Einstein Medical Center (2003-2013) and 2,248,482 HF-admissions from the 2002-2012 Nationwide Inpatient Sample (NIS) were analyzed separately. Primary outcomes were 30-day HF readmission and in-hospital mortality. Logistic regression models were used to evaluate outcomes. RESULTS: Weekends experienced lower rates of admission and discharge. Mondays experienced the highest admission rate and Fridays experienced the highest discharge rate. Friday was independently associated with highest 30 day HF-readmission rates (Adjusted OR 1.12, CI 1.01-1.23; p=0.02) in addition to risk factors such as African-American race, hypertension, diabetes, hyperlipidemia, end-stage renal disease and coronary artery disease. Within the NIS sample, 85,479 in-hospital deaths (3.8%) were recorded. Compared to weekdays, patients admitted over the weekend had greater comorbidities, higher incidence of acute myocardial infarction (AMI) (15.8% vs. 16.8%; p<0.01), higher Charlson comorbidity index and underwent less procedures such as echocardiography, right heart catheterization, coronary angiography, coronary revascularization or mechanical circulatory support. Weekend HF admission predicted higher in-hospital mortality (aOR 1.07, 95%CI 1.05-1.08; p<0.01) on multivariate analysis. This relationship was applicable for teaching and non-teaching hospitals. CONCLUSION: Friday was associated with the highest discharge and 30-day HF-readmission rate. Weekend HF admissions experienced more AMI, had greater comorbidities, received less cardiac procedures and predicted higher in-hospital mortality. Higher weekend mortality may be related to the greater degree of severity of illness among admitted patients. PMID- 28986060 TI - The prognostic utility of dihomo-gamma-linolenic acid (DGLA) in patients with acute coronary heart disease. AB - BACKGROUND: We previously investigated the prognostic utility of red blood cell (RBC) n-3 fatty acids (FAs) in survivors of an acute myocardial syndrome (ACS) but found no relationship with all-cause mortality and cardiac death or MI after two years. Here we extend our follow-up to 7years, focusing on the potential predictive power of RBC n-6 FAs. METHODS: We included 398 ACS patients presenting with increased troponin-T (TnT) levels for whom baseline RBC FA data were available. Cox regression analysis was used to relate the risk of future events to RBC n-6 FA levels, both continuously and by quartile. RESULTS: At 7-year follow-up, 183 (46.0%) had died, 128 (32.2%) had experienced another MI and 24 (6.0%) had had a stroke. Death or MI occurred in 227 patients (57.0%); and death, MI or stroke in 235 patients (59.0%). In a multivariable Cox regression model for total death, the hazard ratio (HR) in the highest as compared to the lowest quartile of dihomo-gamma-linolenic acid (DGLA) was 0.55 [95% confidence interval (CI), 0.35-0.88, p=0.012, for death or MI [HR 0.62 (95% CI, 0.41-0.94), p=0.025], and for the fully combined endpoint [HR 0.57 (95% CI, 0.38-0.86), p=0.006]. Similar results were found in the per 1-SD analysis. No other RBC n-6 FAs significantly predicted these outcomes in multivariable models. CONCLUSION: RBC DGLA levels had significant independent prognostic value in post-ACS patients. These findings need confirmation, and the possible biochemical pathways by which higher DGLA membrane levels may be cardioprotective should be explored. PMID- 28986061 TI - Adverse cardiovascular outcomes in atrial fibrillation: Validation of the new 2MACE risk score. AB - BACKGROUND: In addition to thromboembolism, atrial fibrillation (AF) may also predispose to major adverse cardiovascular events (MACE) attributable to coronary artery disease (CAD), including myocardial infarction (MI). The 2MACE score (2 points - Metabolic syndrome and Age>=75years, 1 point - MI/revascularization, Congestive heart failure/ejection-fraction <40%, and thrombo-Embolism) was recently proposed to help identify AF patients at risk of MACE. We assessed the predictive validity of the 2MACE score for MACE occurrence in AF patients free of CAD at baseline. METHODS: Non-valvular AF patients (n=794) without CAD (mean-age, 62.5+/-12.1years, metabolic syndrome, 34.0%; heart failure/ejection-fraction <40%, 25.7%; thromboembolism, 9.7%) were prospectively followed for 5years, or until MACE (composite of non-fatal/fatal MI, revascularization and cardiovascular death). At inclusion, CAD was excluded by medical history, exercise-stress testing and/or coronary angiography. Also, the 2MACE score was determined. RESULTS: At follow-up, 112 patients experienced MACE (2.8%/year). The 2MACE score demonstrated adequate discrimination (C-statistic, 0.699; 95% confidence interval [CI], 0.648-0.750; P<0.001) and calibration (Hosmer-Lemeshow P=0.79) for MACE. The score was significantly associated with MACE, with the adjusted Hazard Ratio (aHR) of 1.56 (95%CI, 1.35-1.73; P<0.001). As for individual outcomes, the score predicted MI (n=46; aHR, 1.49; 95%CI 1.23-1.80), revascularization (n=32; aHR, 1.41; 95%CI, 1.11-1.80) and cardiovascular death (n=34; aHR, 1.43; 95%CI, 1.14 1.81), all P<0.001. CONCLUSIONS: The 2MACE score successfully predicts future MACE, including incident MI, coronary revascularization and cardiovascular death in AF patients free of CAD at baseline. It may have a role in risk-stratification and primary prevention of MACE in AF patients. PMID- 28986063 TI - Utility of the 0-hour/1-hour high-sensitivity cardiac troponin T algorithm in Asian patients with suspected non-ST elevation myocardial infarction. AB - BACKGROUND: A rapid rule-out or rule-in protocol based on the 0-hour/1-hour algorithm using high-sensitivity cardiac troponin T is recommended by the European Society of Cardiology. However, Asian data are not available. METHODS: This prospective cohort study included 413 patients with suspected non-ST elevation myocardial infarction in 3 hospitals in Japan and Taiwan from November 2014 to April 2017. Patients were divided into 3groups-rule-out, observe, and rule-in-according to the algorithm. Major adverse cardiovascular events were evaluated at the 30-dayfollow-up. RESULTS: The algorithm ruled out acute myocardial infarction (AMI) in 171 patients with a negative predictive value and sensitivity of 100% (95% confidential interval [CI], 96.8%-100%) and 100% (95% CI, 88.0%-100%), respectively, in the rule-out group. None of the patients were diagnosed with AMI. Among the 127 patients classified into the rule-in group, 47 were diagnosed as having AMI. The positive predictive value and specificity were 33.1% (95% CI, 25.1%-41.9%) and 66.3% (95% CI, 60.2%-72.0%), respectively. Elective catheter intervention was required in 13 patients (5 in the rule-out group, 8 in the observe group) by the 30-dayfollow-up. The Framingham Risk Score (FRS) identified moderate risk in 5 patients and high risk in 8, while the Global Registry of Acute Coronary Events (GRACE) 2.0 risk score identified low risk in 6 patients and moderate risk in 7. CONCLUSION: The ESC0-hour/1-hour algorithm could be sufficient in Asian patients. The combination with FRS may be more precise than that with the GRACE 2.0 risk score. PMID- 28986062 TI - Quality control of regional wall motion analysis in stress Echo 2020. AB - BACKGROUND: The trial "Stress Echo (SE) 2020" evaluates novel applications of SE beyond coronary artery disease. The aim of the study was control quality and harmonize reading criteria. METHODS: One reader from 78 centers of the SE 2020 network asked for credentials to read a set of 20 SE video-clips selected by the core lab. All aspiring centers met the pre-requisite of high-volume and the years of experience in SE ranged from 5 to 31years (mean value 18years). The diagnostic gold standard was a reading by the core lab. The a priori determined pass threshold was 18/20 (>=90%). RESULTS: Of the initial 78 who started, 57 completed the first attempt: individual readers' score on first attempt ranged from 07/20 to 20/20 (accuracy from 35% to 100%, mean 78.7+/-13%) and 44 readers passed it. There was a very poor correlation between years of experience and the reader's score on first attempt (r=-0.161, p=0.231). Of the 13 readers who failed the first attempt, 12 took it again after the web-based session and their accuracy improved (74% vs. 96%, p<0.001). The kappa inter-observer agreement before and after web-based training was 0.59 on first attempt and rose to 0.91 on the last attempt. CONCLUSIONS: In SE reading, the volume of activity or years of experience is not synonymous with diagnostic quality. Qualitative analysis and operator-dependence can become a limiting weakness in clinical practice, in the absence of strict pathways of learning, credentialing and audit. PMID- 28986064 TI - Liposomes entrapping beta-cyclodextrin/ibuprofen inclusion complex: Role of the host and the guest on the bilayer integrity and microviscosity. AB - Multilamellar vesicles (MLVs) from 1-palmitoyl-2-oleoyl-sn-glycero-3 phosphocholine (POPC) were prepared by using the dehydration-rehydration method. The beta-cyclodextrin/Ibuprofen inclusion complex (beta-CD/Ibu) was formed and solubilised into the aqueous compartments of the investigated vesicles. The resulting POPC MLVs entrapping beta-CD/Ibu complex were essentially homogeneous in shape as demonstrated by Transmission Electron Microscopy (TEM). The liposomal stability was determined at 37.0+/-0.1 degrees C by following the outflux rate of 5(6)-carboxyfluorescein (CF) at pH 7.40, while the membrane microviscosity was estimated by the ratio of the fluorescence intensities of pyrene in excimer and monomer state. The results presented herein confirm that interactions between POPC and beta-CD occur and suggest that associations between POPC and Ibuprofen are also involved in the properties of the investigated liposomes. PMID- 28986065 TI - A little rein on addiction. AB - Rewarding and aversive experiences influence emotions, motivate specific behaviors, and modify future action in animals. Multiple conserved vertebrate neural circuits have been discovered that act in a species-specific manner to reinforce behaviors that are rewarding, while attenuating those with an adverse outcome. A growing body of research now suggests that malfunction of the same circuits is an underlying cause for many human disorders and mental ailments. The habenula (Latin for "little rein") complex, an epithalamic structure that regulates midbrain monoaminergic activity has emerged in recent years as one such region in the vertebrate brain that modulates behavior. Its dysfunction, on the other hand, is implicated in a spectrum of psychiatric disorders in humans such as schizophrenia, depression and addiction. Here, I review the progress in identification of potential mechanisms involving the habenula in addiction. PMID- 28986066 TI - The crosstalk between Sirt1 and Keap1/Nrf2/ARE anti-oxidative pathway forms a positive feedback loop to inhibit FN and TGF-beta1 expressions in rat glomerular mesangial cells. AB - Oxidative stress aroused by advanced glycation-end products (AGEs) is a culprit in the pathological progression of diabetic nephropathy. Both Sirt1 and the Keap1/Nrf2/ARE anti-oxidative pathway exert crucial inhibitory effects on the development of diabetic nephropathy. Our previous study has confirmed that Sirt1 activation can inhibit the upregulation of fibronectin (FN) and transforming growth factor-beta1 (TGF-beta1) by promoting Keap1/Nrf2/ARE pathway in glomerular mesangial cells (GMCs) challenged with AGEs. However, the underlying mechanism needs further investigation. Here, we found that concomitant with deacetylating and reducing the ubiquitination levels of Nrf2, Sirt1 significantly enhanced the activity of Keap1/Nrf2/ARE pathway including decreasing Keap1 expression, promoting the nuclear content, ARE-binding ability, and transcriptional activity of Nrf2, augmenting the protein levels of heme oxygenase 1, a target gene of Nrf2, which eventually quenched ROS overproduction and alleviating FN and TGF beta1 accumulation in AGEs-treated GMCs. And depletion of Nrf2 blocked those renoprotective effects of Sirt1. Interestingly, Nrf2 also positively regulated Sirt1 at the protein expression and deacetylase activity levels as evidenced by tert-Butylhydroquinone and specific siRNA targeting Nrf2 to downregulate FN and TGF-beta1. In conclusion, the current study basically demonstrated that the crosstalk between Sirt1 and Keap1/Nrf2/ARE anti-oxidative pathway forms a positive feedback loop to inhibit the protein expressions of FN and TGF-beta1 in AGEs-treated GMCs. PMID- 28986068 TI - Effectiveness of omega-3 fatty acid supplementation in patients with Alzheimer disease: A systematic review and meta-analysis. AB - INTRODUCTION: Alzheimer disease (AD) is a neurodegenerative disease characterised by progressive dementia associated with global cognitive dysfunction. METHODS: We conducted a systematic review and meta-analysis of clinical trials evaluating omega-3 supplementation in patients with AD. OBJECTIVE: To determine if there is scientific evidence of the effectiveness of omega-3 supplementation in improving cognitive function in patients with AD. SEARCH STRATEGY: We included only randomised controlled trials (RCTs) from the following databases: Medline, Cochrane Central, Cinahl, and LILACS. An electronic search was also conducted using Google Scholar. STUDY SELECTION: Six articles met the eligibility criteria. The risk of bias was assessed following the Cochrane method. CONCLUSION: There is no consistent evidence to support the effectiveness of omega-3 supplementation in improving cognitive function in AD patients in the short and medium term. PMID- 28986067 TI - T cell responses in senior patients with community-acquired pneumonia related to disease severity. AB - Senior individuals older than 65 years of age are at a disproportionally higher risk of developing pneumonia. Impaired capacity to defend against airway infections may be one of the reasons. It is generally believed that weaker regulatory T cell responses may be beneficial to host defense against pathogens. In senior patients with community-acquired bacterial pneumonia, we investigated the frequencies and functions of regulatory T cells. Interestingly, we found that compared to age- and sex-matched healthy controls, senior pneumonia patients presented lower frequencies of Foxp3-expressing and Helios-expressing CD4+ T cells. The quantity of Foxp3 and Helios being expressed, measured by their mRNA transcription levels, was also lower in CD4+ T cells from pneumonia patients. Furthermore, following TCR and TGF-beta stimulation, pneumonia patients presented impaired capacity to upregulate Foxp3 and Helios. Functional analyses revealed that CD4+ T cells from pneumonia patients secreted lower amounts of IL-10 and TGF beta, two cytokines critical to regulatory T cell-mediated suppression. Also, the expression of granzyme B and perforin, which were cytolytic molecules potentially utilized by regulatory T cells to mediate the elimination of antigen-presenting cells and effector T cells, were reduced in CD4+CD25+ T cells from senior pneumonia patients. In addition, the CD4+CD25+ T cells from senior pneumonia patients presented reduced capacity to suppress effector CD4+ and CD8+ T cell proliferation. Moreover, the value of pneumonia severity index was inversely correlated with several parameters of regulatory T cell function. Together, our results demonstrated that senior pneumonia patients presented a counterintuitive impairment in regulatory T cell responses that was associated with worse prognosis. PMID- 28986069 TI - Accuracy and usefulness of aortic annular measurement using real-time three dimensional transesophageal echocardiography: Comparison with direct surgical sizing. AB - BACKGROUND: There is a paucity of data that demonstrates a clinical impact of anatomical measurements of the aortic annulus by three-dimensional (3D) transesophageal echocardiography (TEE) on surgical aortic valve replacement (AVR). The aim of this study is to validate the accuracy of 3D TEE measurements compared with the direct intraoperative annular diameter and to investigate an impact of 3D TEE on a prediction of AVR with aortic annular enlargement (AAE). METHODS AND RESULTS: We retrospectively enrolled 61 patients who underwent both two-dimension (2D) and 3D TEE and transthoracic echocardiography (TTE) before AVR. The annular diameters were measured noninvasively with 2D TEE (D2D) and TTE (DTTE) in a classical manner and the area- and perimeter-derived annular diameters (Darea, Dperim) were measured from using 3D TEE analysis. Intraoperative annular diameter was measured with the manufacture's sizer (Dintraope). Darea showed the best agreement with Dintraope in the Bland-Altman analysis. Darea, Dperim, D2D, and DTTE correlated well with Dintraope (r=0.821, 0.820, 0.532, and 0.610, respectively; all p<0.001). Three patients underwent AVR with AAE and the specificity of Dperim for prediction of AAE was significantly higher than D2D (p=0.008). CONCLUSIONS: 3D TEE measurement of aortic annular diameter showed better agreement with the direct intraoperative measurement than 2D TEE and TTE measurements. 3D TEE measurement could predict AVR with AAE more accurately than 2D TEE and TTE measurements. PMID- 28986070 TI - Remembering Corrado Vassanelli. PMID- 28986071 TI - Severe Asthma and the Primary Care Provider: Identifying Patients and Coordinating Multidisciplinary Care. AB - Without proper care, patients with severe forms of asthma face substantial medical risks, marked reductions in quality of life, and other significant disease-related burdens. Therefore, it is essential that primary care clinicians and other healthcare providers are adept at identifying cases of severe asthma on the basis of symptom control, exacerbation risks, and the need for relatively aggressive treatment regimens (eg, high-dose inhaled corticosteroids with long acting controller medications or frequent oral corticosteroid use). Engaging and educating affected individuals as part of ongoing treatment planning are best achieved with a good understanding of patients' own insights into their disease and management challenges that often arise in busy healthcare practices. This includes effectively communicating with patients about the implications of their diagnosis and potential treatment strategies that can be accessed via coordinated multidisciplinary care. Expert primary care and specialist faculty have highlighted strategies to identify cases of severe asthma, appropriate referral pathways for these individuals, and considerations on integrating patients' perspectives into clinical decision making across the continuum of care (access to an accredited educational program on these topics is available at http://courses.elseviercme.com/pcp/687). Additionally, this online program is a component of a larger platform of education activities and consolidated clinical resources designed to improve the care of patients with respiratory disorders (http://respiratorycme.elsevierresource.com/). PMID- 28986072 TI - Contraception after medication abortion in the United States: results from a cluster randomized trial. AB - BACKGROUND: Understanding how contraceptive choices and access differ for women having medication abortions compared to aspiration procedures can help to identify priorities for improved patient-centered postabortion contraceptive care. OBJECTIVE: The objective of this study was to investigate the differences in contraceptive counseling, method choices, and use between medication and aspiration abortion patients. STUDY DESIGN: This subanalysis examines data from 643 abortion patients from 17 reproductive health centers in a cluster, randomized trial across the United States. We recruited participants aged 18-25 years who did not desire pregnancy and followed them for 1 year. We measured the effect of a full-staff contraceptive training and abortion type on contraceptive counseling, choice, and use with multivariable regression models, using generalized estimating equations for clustering. We used survival analysis with shared frailty to model actual intrauterine device and subdermal implant initiation over 1 year. RESULTS: Overall, 26% of participants (n = 166) had a medication abortion and 74% (n = 477) had an aspiration abortion at the enrollment visit. Women obtaining medication abortions were as likely as those having aspiration abortions to receive counseling on intrauterine devices or the implant (55%) and on a short-acting hormonal method (79%). The proportions of women choosing to use these methods (29% intrauterine device or implant, 58% short-acting hormonal) were also similar by abortion type. The proportions of women who actually used short-acting hormonal methods (71% medication vs 57% aspiration) and condoms or no method (20% vs 22%) within 3 months were not significantly different by abortion type. However, intrauterine device initiation over a year was significantly lower after the medication than the aspiration abortion (11 per 100 person-years vs 20 per 100 person-years, adjusted hazard ratio, 0.50; 95% confidence interval, 0.28-0.89). Implant initiation rates were low and similar by abortion type (5 per 100 person-years vs 4 per 100 person years, adjusted hazard ratio, 2.41; 95% confidence interval, 0.88-6.59). In contrast to women choosing short-acting methods, relatively few of those choosing a long-acting method at enrollment, 34% of medication abortion patients and 53% of aspiration abortion patients, had one placed within 3 months. Neither differences in health insurance nor pelvic examination preferences by abortion type accounted for lower intrauterine device use among medication abortion patients. CONCLUSION: Despite similar contraceptive choices, fewer patients receiving medication abortion than aspiration abortion initiated intrauterine devices over 1 year of follow-up. Interventions to help patients receiving medication abortion to successfully return for intrauterine device placement are warranted. New protocols for same-day implant placement may also help patients receiving medication abortion and desiring a long-acting method to receive one. PMID- 28986073 TI - "Kissing Nail Technique" for the exchange of intramedullary implants in adjacent peri-implant fractures. AB - One third of the people aged 65 years and over fall every year, and 1-5% of these falls result in a fracture. For these people, history of fracture and surgery become a risk factor for recurrent falls. In osteoporotic patients, repeated fractures often require several osteosynthetic procedures within a short time frame. Despite the lack of biomechanical studies, clinical experience suggests that additional fractures adjacent to implants occur because of the difference in stiffness between the metallic implant and the osteoporotic bone. This requires customized fixation techniques to ensure stability. The technique was first performed in an 81-year old female patient presenting with a dislocated proximal femoral fracture at the tip of a previously implanted distal femoral nail (DFN), and non-union of the old fracture. For this technique, the DFN was advanced until it passed the proximal fracture, thereby reducing both fractures, while a lateral femoral nail (LFN), extra-long and 3 mm thicker than the DFN, was introduced and advanced distally. The LFN was implanted in a "kissing nail technique," meaning the tips of the two nails were touching each other, and all fracture fragments were held in functional reduction. The DFN was slowly pulled backwards and fragment stability was maintained, while both nails passed the distal non-union. The Kissing Nail Technique allows simple, safe and fast reduction of all instable fragments, precise and easy positioning of the proximal entry point by the retrograde guide wire, a minimally invasive procedure, and stable fixation of a periprosthetic fracture. We found this new customized procedure accommodating to the unique anatomical features of a single patient, that can be applied as a strategy especially for osteoporotic patients with periprosthetic fractures. PMID- 28986074 TI - Finite element analysis of the stability of AO/OTA 43-C1 type distal tibial fractures treated with distal tibia medial anatomic plate versus anterolateral anatomic plate. AB - BACKGROUND: The treatment of a pilon fracture type is possible from a medial, an anterolateral approach or both medial and lateral. The aim of study was compare the stability of two different plate fixation of a tibia pilon AO-43C1 type fractures. MATERIAL AND METHODS: In this study, three-dimensional finite element stress analysis was applied using isotropic materials and static linear analysis. Loading of 400 N force was applied to the model of a patient fixed in a standing position. In the model, first the fibula was treated by plating and then in one group the pilon fracture was treated by medial plating, and in the other by anterolateral plating. The displacement and stress values of the fragments of the fracture line were compared of the same points in each model. RESULTS: The magnitude of the displacement of fragments in the total displacement magnitudes of X, Y, Z axis were measured in the medial plate and anterolateral plate. The anterolateral plate results were similar to those of the medial plate and the displacement values in the Y axis were determined to be lower than in the medial plate. CONCLUSION: In AO 43 C1 distal tibia fractures, medial or anterolateral plates can be used, and the results of this study showed similar biomechanical stiffness in the two plates. PMID- 28986075 TI - The scope of upper limb surgery for tetraplegics: Role of tendon transfers and Universal Cuff. AB - OBJECTIVE: The aim of this study was to evaluate the role of tendon transfers and universal cuff in restoring hand function in tetraplegic patients. METHODS: Twenty-one upper limbs on 12 tetraplegic patients (9 males and 3 females); mean age: 42.2 years (range 22-58 years) with a spinal cord injury at or distal to C6, were included in this study. Key pinch was restored using Brachioradialis to Flexor Pollicis Longus transfer and hook using Pronator Teres to Flexor Digitorum Profundus transfer. The gains achieved were measured objectively at six months and at final follow up, the average follow up being 26 months. The functional outcome was assessed using the Modified Lamb and Chan score. RESULTS: Average value was 1.67 kg for key pinch and 2.58 kg for hook grip at final follow up. The Modified Lamb and Chan score revealed good to fair outcome in 75% of patients. Complications resulted from stretching of transfer and mal-tensioning and were salvaged by the use of a 'Universal Cuff'. CONCLUSION: Surgery should be routinely offered to tetraplegic patients with deficient hand function in whom no recovery is expected after six months following spinal cord injury. Universal Cuff is a good salvage method for patients who refuse re-surgery. LEVEL OF EVIDENCE: Level IV, Therapeutic study. PMID- 28986076 TI - Association between obesity and risk of chronic kidney disease: A nationwide Cohort study in Taiwan. AB - BACKGROUND AND AIMS: Increased body fat relates to enhanced inflammatory cytokine production, which, in turn, activates the renin-angiotensin-aldosterone system and increases the risk of chronic kidney disease (CKD). Herein, we aimed to examine the association between obesity and the risk of CKD in a population representative cohort in Taiwan. METHODS AND RESULTS: A multistage systematic sampling process was applied in the National Health Interview Survey (NHIS) 2000, 2005, and 2009. Participants were interviewed by a standardized face-to-face questionnaire to obtain information on their demographics, socioeconomic status, lifestyle factors, and body mass index (BMI). The BMI values were classified as follows: underweight (<18.5 kg/m2), normal (18.5-23.9 kg/m2), overweight (24-26.9 kg/m2), and obesity (>=27 kg/m2). The NHIS dataset was linked to National Health Insurance claims data to identify the incidence of CKD. Univariate and multivariate Cox proportional hazard models with competing risks were used to investigate the association between BMI and CKD incidence. We analyzed 45,012 subjects (mean age, 42.03 years; 50.09% males). During 374,254 person-years of follow-up, a total of 1913 new-onset CKD cases were identified. Kaplan-Meier curves comparing the four BMI groups revealed a significant difference (p < 0.01, log-rank test). After controlling for confounding factors, the relative risk of incident CKD was significantly higher in the obese group compared to the normal weight group (adjusted hazard ratio = 1.32; 95% confidence interval: 1.17-1.49), with a significant linear trend (p < 0.01). CONCLUSION: Obesity was suggested as an independent risk factor for CKD. Further studies focusing on the effect of losing weight on CKD prevention are warranted. PMID- 28986077 TI - Inverse relations of serum phosphatidylcholines and lysophosphatidylcholines with vascular damage and heart rate in patients with atherosclerosis. AB - BACKGROUND AND AIMS: The rapidly growing discipline of lipidomics allows the study of a wide spectrum of lipid species in body fluids and provides new insights into the pathogenesis of cardiovascular disease. We investigated serum phosphatidylcholine (PC) and lysophosphatidylcholine (lysoPC) species in relation to arterial stiffness, hemodynamics, and endothelial dysfunction in symptomatic patients with atherosclerosis and in healthy controls. METHODS AND RESULTS: Thirty-two patients with peripheral arterial disease (age 61.7 +/- 9.0 years), 52 patients with coronary artery disease (age 63.2 +/- 9.2 years), and 40 apparently healthy controls (age 60.3 +/- 7.1 years) were studied. Serum levels of 90 glycerophospholipids were determined with the AbsoluteIDQTM p180 kit (BIOCRATES Life Sciences AG, Innsbruck, Austria). The technique of applanation tonometry was used for non-invasive pulse wave analysis and carotid-femoral pulse wave velocity (cf-PWV) assessment. Decreased serum levels of several individual PC and lysoPC species (e.g., PC aa C28:1, PC aa C30:0, PC aa C32:2, PC ae C30:0 and PC ae C34:2, lysoPC a C18:2) were observed for the patient groups in comparison to the healthy subjects. In addition, a considerable number of PCs and lysoPCs were inversely related to either cf-PWV, heart rate, asymmetric dimethylarginine (ADMA) or ADMA/arginine for patients with symptomatic atherosclerosis but not for the controls. CONCLUSION: We found altered relationships between PC and lysoPC profiles, inflammation, and arterial function in atherosclerotic patients, compared to healthy subjects. PMID- 28986078 TI - Are bariatric and metabolic surgeries synonymous? - A nutritional view. PMID- 28986079 TI - Complex migration of antibiotic resistance in natural aquatic environments. AB - Antibiotic resistance is a worsening global concern, and the environmental behaviors and migration patterns of antibiotic resistance genes (ARGs) have attracted considerable interest. Understanding the long-range transport of ARG pollution is crucial. In this study, we characterized the dynamics of ARG changes after their release into aquatic environments and demonstrated the importance of traditional chemical contaminants in the transmission mechanisms of ARGs. We hypothesized that the main route of ARG proliferation switches from active transmission to passive transmission. This antibiotic-dominated switch is motivated and affected by non-corresponding contaminants. The effect of anthropogenic activities gradually weakens from inland aquatic environments to ocean environments; however, the effect of changes in environmental conditions is enhanced along this gradient. The insights discussed in this study will help to improve the understanding of the distribution and migration of ARG pollution in various aquatic environments, and provide a modern perspective to reveal the effect of corresponding contaminants and non-corresponding contaminants in the process of antibiotic resistance proliferation. PMID- 28986080 TI - Chronic nitrate exposure alters reproductive physiology in fathead minnows. AB - Nitrate is a ubiquitous aquatic pollutant that is commonly associated with eutrophication and dead zones in estuaries around the world. At high concentrations nitrate is toxic to aquatic life but at environmental concentrations it has also been purported as an endocrine disruptor in fish. To investigate the potential for nitrate to cause endocrine disruption in fish, we conducted a lifecycle study with fathead minnows (Pimephales promelas) exposed to nitrate (0, 11.3, and 56.5 mg/L (total nitrate-nitrogen (NO3-N)) from <24 h post hatch to sexual maturity (209 days). Body mass, condition factor, gonadal somatic index (GSI), incidence of intersex, and vitellogenin induction were determined in mature male and female fish and plasma 11-keto testosterone (11-KT) was measured in males only. In nitrate-exposed males both 11-KT and vitellogenin were significantly induced when compared with controls. No significant differences occurred for body mass, condition factor, or GSI among males and intersex was not observed in any of the nitrate treatments. Nitrate-exposed females also had significant increases in vitellogenin compared to controls but no significant differences for mass, condition factor, or GSI were observed in nitrate exposed groups. Estradiol was used as a positive control for vitellogenin induction. Our findings suggest that environmentally relevant nitrate levels may disrupt steroid hormone synthesis and/or metabolism in male and female fish and may have implications for fish reproduction, watershed management, and regulation of nutrient pollution. PMID- 28986081 TI - Blood concentrations of PCBs and DDTs in an avian predator endemic to southern Africa: Associations with habitat, electrical transformers and diet. AB - Persistent pollutants such as organochlorine compounds (OCs) have been highlighted as a cause of population decline in avian predators. Understanding patterns of OCs contamination can be crucial for the conservation of affected species, yet little is known on these threats to African raptors. Here we report on OC concentrations in an endangered predator endemic to southern Africa, the Black Harrier Circus maurus. Blood samples were collected in 2012-2014 from wild nestlings (n = 90) and adults (n = 23) in south-western South Africa, where agriculture and urbanization have developed rapidly since the 1950s. Polychlorinated biphenyl (SigmaPCB) and dichlorodiphenyltrichloroethane (SigmaDDT, for p,p'-DDT + p,p'-DDE) were detected in 79% and 84% of sampled individuals, respectively, with varying concentrations among demographic groups: nestlings had significantly higher SigmaPCB and p,p'-DDT concentrations than adults, while adults had higher levels of p,p'-DDE than nestlings. Levels of SigmaPCB significantly increased with an index of electric transformer density, a measure of the number and power of electric transformers around active nests. We propose this index as a useful tool for assessing SigmaPCB exposure risk in other wildlife. Levels of p,p'-DDE significantly increased with the proportion of wetlands within the breeding territory, and also with the proportion of bird biomass in the diet. No association was found between OC levels and the protected area status of nesting sites. Physiological effects of contaminants were also manifest in increased white blood cell counts with higher p,p'-DDT levels. Heterophil to lymphocyte ratio increased with higher SigmaPCB levels, suggesting increased physiological stress and reduced immunity in contaminated individuals. Our results suggest that OCs are still a current cause of concern for endangered Black Harriers, as well as other sympatric predators. PMID- 28986082 TI - Fifteen years of imposex and tributyltin pollution monitoring along the Portuguese coast. AB - IMO's Anti-Fouling Systems convention banned the use of organotin-based antifouling systems in 2008 as the ultimate effort to stop tributyltin (TBT) inputs into the marine environment. One of the hazardous effects of TBT is imposex (the superimposition of male sexual characters onto gastropod females), a phenomenon that may cause female sterility and the gastropod populations decline. Despite previous European Union legislation had already been shown effective in reducing the imposex levels along the Portuguese coast, this study intends to confirm these decreasing trends after 2008 and describe the global evolution in the last 15 years. Imposex levels were assessed in two bioindicators - the dog whelk Nucella lapillus and the netted-whelk Nassarius reticulatus (Gastropoda, Prosobranchia) - in 2011 and 2014, and the results were compared with previous years. Both species showed progressive decreasing trends in imposex levels over the last 15 years; median values of the vas deferens sequence index (VDSI) fell from 3.96 to 0.78 in N. lapillus and from 3.39 to 0.29 in N. reticulatus. The temporal/spatial evolution of imposex suggests an apparent shift of TBT hotspots, being now restricted to fishing ports and marinas in detriment of large commercial harbours where TBT levels fell rapidly. Butyltins were measured in the whole tissues of N. lapillus females collected in 2014: monobutyltin (MBT) varied from < DL (detection limit: 1 ng Sn/g) to 13 ng Sn/g dw, dibutyltin (DBT) from 2.2 to 27 ng Sn/g dw and TBT from 1.5 to 55 ng Sn/g dw. Although TBT body burden has declined over time, the butyltin degradation index ([MBT]+[DBT])/[TBT] exhibited values < 1 in c. a. 90% of the sites assessed, suggesting that recent TBT inputs are still widespread in the Portuguese coast eventually due to illegal use of TBT antifouling systems and TBT desorption from sediments. PMID- 28986083 TI - The effect of sewage sludge fertilization on the concentration of PAHs in urban soils. AB - This paper analyses sources of sixteen PAHs - polycyclic aromatic hydrocarbons in urbanized areas by using selected diagnostic ratios. Simultaneously, an attempt was made to determine how sewage sludge changes PAHs content in urbanized areas soils. In the experiment three lawns along the main roads in Bialystok with different traffic intensity, three doses of sewage sludge and two years of study were considered. There was no effect of fertilization with sewage sludge on the sum of 16 PAHs in urban soil samples, nevertheless, the sum of 16 PAHs was reduced from 2.6 in 2011 to 2.3 mg/kg in 2012. Among 16 tested PAHs compounds, benzo[a]pyrene was the most dominant compound in samples collected in both years about 15% of all PAHs. The results suggest that application of sludge into the soil did not influence the concentration of 2-3-ring, 4-ring and 5-6-ring PAHs. For the objects fertilized with a dose 150.0 Mg/ha, of sludge the total sum of potentially carcinogenic PAHs in the urban soil lowered by approximately 68% in comparison with the control plots. PAHs contamination of the urban soil samples resulted from the influence of coal, petroleum and biomass combustion. Moreover, PAHs can enter soil via at mospheric deposition. PMID- 28986084 TI - On the functional significance of retrieval mode: Task switching disrupts the recollection of conceptual stimulus information from episodic memory. AB - Episodic memory retrieval is assumed to be associated with the tonic cognitive state of retrieval mode. Despite extensive research into the neurophysiological correlates of retrieval mode, as of yet, relatively little is known about its functional significance. The present event-related potential (ERP) study was aimed at examining the impact of retrieval mode on the specificity of memory content retrieved in the course of familiarity and recollection processes. In two experiments, participants performed a recognition memory inclusion task in which they had to distinguish identically repeated and re-colored versions of study items from new items. In Experiment 1, participants had to alternate between the episodic memory task and a semantic task requiring a natural/artificial decision. In Experiment 2, the two tasks were instead performed in separate blocks. ERPs locked to the preparatory cues in the test phases indicated that participants did not establish retrieval mode on switch trials in Experiment 1. In the absence of retrieval mode, neither type of studied item elicited ERP correlates of familiarity-based retrieval (FN400). Recollection-related late positive complex (LPC) old/new effects emerged only for identically repeated but not for conceptually identical but perceptually changed versions of study items. With blocked retrieval in Experiment 2, both types of old items instead elicited equivalent FN400 and LPC old/new effects. The LPC data indicate that retrieval mode may play an important role in the successful recollection of conceptual stimulus information. The FN400 results additionally suggest that task switching may have a detrimental effect on familiarity-based memory retrieval. PMID- 28986085 TI - Ovatodiolide isolated from Anisomeles indica induces cell cycle G2/M arrest and apoptosis via a ROS-dependent ATM/ATR signaling pathways. AB - Ovatodiolide was isolated from the traditional Chinese medicinal herb Anisomeles indica, possesses anti-bacterial and anti-inflammatory properties; however, the anti-cancer activity and its mechanisms have been limitedly reported. This study aimed to examine the effect and molecular action of ovatodiolide in lung cancer cells. Cell cycle distribution and reactive oxygen species (ROS) generation were measured by flow cytometry. Apoptosis was detected by propidium iodide/annexin V staining and TUNEL assay. DNA damage was investigated by comet assay and gamma H2AX staining. Caspase activity was determined using caspase fluorometric kits. Moreover, protein levels were examined by western blot. Ovatodiolide provoked reactive oxygen species generation and DNA damage, as well as inhibited cell growth and induced apoptosis in human lung cancer A549 and H1299 cell lines. DNA damage-related molecules, ATM/ATR and CHK1/CHK2 were activated by ovatodiolide. Moreover, ovatodiolide-mediated G2/M arrest was associated with the decrease of Cyclin B1 and CDC25C levels, and increase of p21WAF1/CIP1 expression. Additionally, ovatodiolide-triggered apoptosis was through both intrinsic and extrinsic pathways characterized by the elevating PUMA, Bax, and DR5 proteins, decreasing Bcl-2 and Mcl-1, and activating caspase-8, caspase-9 and caspase-3. Caffeine, an ATM/ATR inhibitor, rescued ovatodiolide-mediated cell cycle arrest and apoptosis, but not reactive oxygen species generation. Nevertheless, antioxidant N-acetyl-cysteine completely blocked ovatodiolide-mediated molecular events, G2/M arrest, and apoptosis. These observations suggest that ovatodiolide stimulates reactive oxygen species generation, causes oxidative stress and DNA damage; subsequently, provokes DNA damage signaling pathways, eventually leads to block cell cycle at G2/M phase and trigger apoptosis in lung cancer A549 and H1299 cells. PMID- 28986086 TI - Functional physical training improves women's military occupational performance. AB - : The U.S. Armed Forces have recently approved full integration of women into combat roles. Physical fitness demands for executing Military Occupational Specialties (MOS) are substantial; thus lifting and load carriage capability improvements are desirable. OBJECTIVES: To determine if a specially-designed physical conditioning program could lessen the gap between the performance of male and female Soldiers in lifting and load carriage and thereby enable women to meet the requirements of most, if not all, Army MOSs. METHODS: Forty women participated in a 24-week physical training program, which included resistance training, long-distance running, backpacking, and specialized drills. Pre- and post-tests of occupational and physical performance measures were conducted before and after training. Repeated measures analysis of variance were used to determine statistically significant differences among the pre-, mid- and posttests. RESULTS: Women increased maximal occupational lifting strength 12-20 kg, added 9-34 repetitions in lifting endurance, increased 0.23 m in jumping performance, added 46 repetitions in local muscular endurance, and decreased load carriage for time by 3.7-8.6 min. Women scored within 82-94% of untrained male scores for aerobic capacity and muscular endurance after training. CONCLUSION: Women's ability to perform physically-demanding military occupational tasks was significantly improved following 6 months of concurrent training, with emphasis on load carriage and lifting. The percentage of women that qualified for current "heavy" and "very heavy" MOSs was initially 24%, but increased to 78% after training. A resistance training program of 6+ months can adequately prepare women for "heavy" to "very heavy" MOS's. PMID- 28986087 TI - Risk factors for injury associated with low, moderate, and high mileage road marching in a U.S. Army infantry brigade. AB - OBJECTIVES: Road marching is an important physical training activity that prepares soldiers for a common occupational task. Continued exploration of risk factors for road marching-related injuries is needed. This analysis has assessed the association between modifiable characteristics of physical training and injury risk. METHODS: Injuries in the previous 6 months were captured by survey from 831 U.S. Army infantry soldiers. Road marching-related injuries were reported as those attributed to road marching on foot for specified distances while carrying equipment. Frequencies, means, and relative risk ratios (RR) for road marching-related injury with 95% confidence intervals (CI) were calculated. Adjusted odds ratios (OR) and 95% CI were calculated for leading risk factors using multivariable logistic regression. DESIGN: Retrospective cohort study. RESULTS: Half (50%) of reported injuries were attributed to road marching or running. When miles of exposure were considered, injury risk during road marching was higher than during running (RRroad marching/running=1.8, 95% CI: 1.38-2.37). A higher product of road marching distance and weight worn (pound-miles per month) resulted in greater injury risk (RR>=1473 pound-miles/<1472=1.92, 95% CI: 1.17-2.41). Road marching-related injuries were associated with carrying a load >25% of one's body weight (OR>25%/1-20%=2.09, 95% CI: 1.08-4.05), having high occupational lifting demands (OR50-100+lbs/25-50lbs=3.43, 95% CI: 1.50-7.85), road marching >=5 times per month (OR>=5 times/4 times=2.11, 95% CI: 1.14-3.91), and running <4 miles per week during personal physical training (OR0/>=10 miles/week=3.56, 95% CI: 1.49-8.54, OR1-4/>=10 miles/week=4.14, 95% CI: 1.85 9.25). CONCLUSIONS: Ideally, attempts should be made to decrease the percentage of body weight carried to reduce road marching-related injuries. Since this is not always operationally feasible, reducing the cumulative overloading from both physical training and occupational tasks may help prevent injury. PMID- 28986088 TI - Expression of tyrosine kinase receptor AXL is associated with worse outcome of metastatic renal cell carcinomas treated with sunitinib. AB - BACKGROUND: Renal cell carcinoma (RCC) represents 2%-3% of all cancers of the Western countries. Currently, sunitinib, a receptor tyrosine kinase inhibitor, particularly of PDGF and VEGF receptors, is the first-line therapy for metastatic RCC (mRCC), with significant improvement in clinical outcome. However, there is a lack of predictive biomarkers of sunitinib response. Recently, others and our group suggested that the receptor tyrosine kinase AXL may modify the response to sunitinib. OBJECTIVE: To study the expression of AXL in a series patients with of mRCC treated with sunitinib and to correlate it with patient's clinic pathological features and therapeutic response. MATERIAL AND METHODS: Sixty-four patients with mRCC (51 clear cell carcinomas (CCCs) and 13 non-CCCs) were evaluated for AXL expression by immunohistochemistry in the primary tumor. RESULTS: AXL positivity was observed in 47% (30/64) of cases, namely in 43% (22/51) of CCCs and 61% (8/13) of non-CCC. Considering only the clear cell subtype, the univariate analysis showed that AXL expression was statistically associated with a poor prognosis, with a median overall survival of 13 months vs. 43 months in patients with negative AXL. In this subtype, along with the AXL positivity, other prognostic factors were absence of nephrectomy, Karnofsky performance status, more than 1 site of metastasis and liver metastasis. Moreover, AXL expression was associated with shorter progression to sunitinib. Overall, the multivariate survival analysis showed that absence of nephrectomy (HR = 4.85, P = 0.001), more than 1 site of metastasis (HR = 2.99, P = 0.002), bone metastasis (HR = 2.95, P = 0.001), together with AXL expression (HR = 2.01, P = 0.048) were independent poor prognostic factor in patients with mRCC. CONCLUSION: AXL expression was associated with worse clinical outcome and may be an important prognostic biomarker in sunitinib-treated patients with metastatic renal cell carcinoma. PMID- 28986089 TI - Anterior deflected urinary stream. AB - We present a case of anterior deflected urinary stream (ADUS) secondary to meatal shelf with no dysfunctional voiding symptoms (DV). The video illustrates the presentation, operative management and literature review. Meatal deformity in girls has been described in association with DV. Hoebeke et al. highlighted the strong correlation between meatal abnormality and non-neurogenic bladder dysfunction in girls. They demonstrated that girls with ADUS had more severe dysfunction on urodynamics. Klijn et al. prospectively evaluated the effect of surgical meatal correction in girls with ADUS. They found that 39% of female patients with DV had ADUS, 50% of them were free of symptoms following surgical correction. This is the first reported case of an isolated ADUS without DV. Early correction of the anomaly is advocated to limit social distress, and potentially prevent development of DV. PMID- 28986090 TI - Urinary tract infection in children: Diagnosis, treatment, imaging - Comparison of current guidelines. AB - BACKGROUND AND OBJECTIVE: Urinary tract infection (UTI) is a frequent disorder of childhood, yet the proper approach for a child with UTI is still a matter of controversy. The objective of this study was to critically compare current guidelines for the diagnosis and management of UTI in children, in light of new scientific data. METHODS: An analysis was performed of the guidelines from: American Academy of Pediatrics (AAP), National Institute for Health and Care Excellence (NICE), Italian Society of Pediatric Nephrology, Canadian Paediatric Society (CPS), Polish Society of Pediatric Nephrology, and European Association of Urology (EAU)/European Society for Pediatric Urology (ESPU). Separate aspects of the approach for a child with UTI, including diagnosis, treatment and further imaging studies, were compared, with allowance for recent research in each field. CONCLUSIONS: The analyzed guidelines tried to reconcile recent reports about diagnosis, treatment, and further diagnostics in pediatric UTI with prior practices and opinions, and economic capabilities. There was still a lack of sufficient data to formulate coherent, unequivocal guidelines on UTI management in children, with imaging tests remaining the main area of controversy. As a result, the authors formulated their own proposal for UTI management in children. PMID- 28986091 TI - The role of adenotonsillectomy in the treatment of primary nocturnal enuresis in children: A systematic review. AB - INTRODUCTION: Primary nocturnal enuresis (PNE) is a challenging condition for physicians, patients and families. Although the etiology remains unclear, sleep disordered breathing (SDB) and sleep apnea have been suggested to play an important role. Recent research has suggested a potential therapeutic benefit of adenotonsillectomy (T&A) and surgical management of upper airway obstruction in the treatment of PNE. OBJECTIVE: The aim was to conduct a systematic review of relevant literature to determine the effectiveness of T&A in treating children aged 2-19 years with PNE. STUDY DESIGN: This was a systematic review using a comprehensive electronic search strategy that included PubMed, Embase, CINAHL, Cochrane Library, conference proceedings, and the gray literature up to July 2015. We included all studies of children aged 2-19 years with PNE and SDB who underwent T&A. The primary outcome was resolution of PNE following surgery. Observational studies and randomized trials were reviewed. Risk of bias assessment and meta-analyses of included studies were performed. RESULTS: We screened 3254 citations; following title and abstract screening, 42 studies were selected for full-text screening by two independent reviewers. We included 18 studies (890 patients) in our final analysis. All studies were observational and only one included a control group. Meta-analysis of proportions of all (18) studies revealed a pooled complete resolution rate of 51% (43-60%), with significant heterogeneity among studies (I2 = 82.2%). Partial resolution was seen in 20% (14-27%), with similar heterogeneity to the complete resolution group. Sensitivity analysis including only studies with a low risk of bias and with patients >=5 years (n = 244 patients) yielded a complete resolution rate of 43% (36-49%) with minimal heterogeneity (I2 = 0%; figure). CONCLUSION: In our systematic review, T&A resulted in improvement of nocturnal enuresis in more than 60% of patients, with complete resolution rates in excess of 50%. Findings were persistent on meta-analysis focused only on studies including older patients (>=5 years) and those with short follow-up after surgery (<=3 months), which imply a higher cure rate than would be expected based on natural history alone. The limitations of this review include the lack of controlled trials, the overall quality of the evidence reviewed and the heterogeneity between included studies. The role for systematic investigation and treatment of sleep disorders in patients with PNE should be scrutinized further, since a near 50% complete resolution rate for PNE may be expected with T&A in some settings. PMID- 28986092 TI - Population-based HPV vaccination programmes are safe and effective: 2017 update and the impetus for achieving better global coverage. AB - Persistent oncogenic human papillomavirus (HPV) is the cause of cervical cancer, as well as cancers of the anus, penis, vulva, vagina and oropharynx. There is good evidence that prophylactic HPV vaccines are immunogenic and effective against targeted-type HPV infections and type-specific genital lesions, including high-grade cervical intraepithelial neoplasia (CIN), when administered prior to HPV infection. There is good evidence that HPV vaccines are safe in population usage, with the most frequent adverse event being injection-site reactions. There is evidence to support some cross-protection against non-targeted types occurring following the administration of HPV vaccines. There is limited evidence suggesting that HPV vaccines may be beneficial in preventing future disease in women treated for high-grade CIN. This chapter focuses on the accumulated evidence regarding the global use of the three licensed HPV vaccines including safety, immunogenicity, duration of protection, effectiveness, coverage to date and barriers to higher coverage. PMID- 28986093 TI - Prognosis of women with stage I endometrioid endometrial cancer and synchronous stage I endometrioid ovarian cancer. AB - OBJECTIVE: Synchronous endometrial and ovarian cancer with endometrioid histology at two cancer sites typically presents with early-stage disease and is thought to have a good prognosis. We examined the survival of women with early-stage endometrioid endometrial cancer who had synchronous early-stage endometrioid ovarian cancer. METHODS: This is a retrospective case-control study examining the Surveillance, Epidemiology, and End Result Program between 1973 and 2013. Survival of women with stage I endometrioid endometrial cancer with stage I endometrioid ovarian cancer (n=839) were compared to women with stage I endometrioid endometrial cancer without synchronous ovarian cancer (n=123,692) after propensity score matching. RESULTS: Women with synchronous stage I endometrioid ovarian cancer were more likely to be diagnosed recently, be younger, have stage IA disease, grade 1 tumors, to have undergone lymphadenectomy, and were less likely to receive radiotherapy compared to those without synchronous ovarian cancer (all, P<0.001). In a propensity score matched model, the presence of synchronous ovarian cancer was not associated with endometrial cancer-specific survival (10-year rates 96.0% versus 95.3%, P=0.97) or overall survival (85.6% versus 87.2%, P=0.10). Among tumors with concordant grades at the two cancer sites, survival was similar regardless of presence of synchronous ovarian tumors (grade 1 tumors, 10-year rate for overall survival, 88.2% versus 89.1%, P=0.40; and grade 2 tumors, 84.0% versus 85.8%, P=0.78). CONCLUSION: Women with stage I endometrioid endometrial cancer with synchronous stage I endometrioid ovarian cancer have a survival outcome similar to those with stage I endometrioid endometrial cancer without synchronous ovarian cancer. PMID- 28986094 TI - PP2A regulates SCF-induced cardiac stem cell migration through interaction with p38 MAPK. AB - AIMS: Previous studies have shown that stem cell factor (SCF) induces the migration of cardiac stem cells (CSCs) and helps to repair myocardial infarctions. Earlier studies on the migration mechanism only focused on the activation of kinases; here, we aimed to explore the functional role of protein phosphatase 2A (PP2A) in SCF-induced CSC migration. MAIN METHODS: CSCs were treated with SCF, PP2A enzymatic activity was measured, the phosphorylation levels of PP2A, p38 MAPK and cofilin were evaluated using western blot. Transwell assay was used to determine the migratory ability of CSCs. KEY FINDINGS: In vitro, SCF induced the phosphorylation of p38 MAPK and cofilin, leading to the migration of CSCs. Cofilin acted as a downstream signal of p38 MAPK. PP2A was involved in this process. Further studies revealed that PP2A was inactivated via phosphorylation at Tyr307 by SCF and the inactivation/phosphorylation was mediated by activated p38 MAPK, as p38 MAPK inhibitor SB203580 or siRNA prevented SCF-induced inactivation and phosphorylation of PP2A. When CSCs were pretreated with PP2A inhibitor (okadaic acid, OA), SCF-induced CSC migration and the downstream signals were enhanced, and the enhancement was reversed when p38 MAPK was blocked. Additionally, co-immunoprecipitation showed a direct interaction of PP2A with p38 MAPK. SIGNIFICANCE: Our results indicated that PP2A regulated the SCF-induced activation of p38 MAPK/cofilin signaling pathway and subsequent migration of CSCs by interaction with p38 MAPK. PMID- 28986095 TI - Modulation of mitochondrial dynamics by treadmill training to improve gait and mitochondrial deficiency in a rat model of Parkinson's disease. AB - PURPOSE: Parkinson's disease (PD) is a progressive degenerative central nervous system disorder that particularly impairs motor function. As PD advances, gait disorders become more pronounced and are often difficult to treat with current pharmacological therapies. Physical activity improves both mobility in and the daily living activities of patients with PD. Mitochondrial alterations and oxidative stress contribute to PD progression. Therefore, the association between mitochondria and exercise in PD and the implicated regulation of mitochondrial proteins was explored in this study. METHODS: In this study, we developed a unilateral 6-hydroxydopamine rat model of PD and executed 4weeks of treadmill training. Motor behavior was evaluated through gait change analysis (the CatWalk method) and rotational testing. The viability of dopaminergic neurons, mitochondrial function, and oxidative stress in the substantia nigra and striatum were investigated through Western blot and immunohistochemical staining. KEY FINDINGS: Treadmill training improved the performance of gait parameters in terms of maximal area, swing speed, stride length, and stance phase; treadmill training also reduced methamphetamine-induced rotation. This training not only improved dopaminergic neuron viability but also recovered mitochondrial function and attenuated oxidative stress in PD rats. The mechanism may be associated with the facilitation of mitochondrial turnover, including facilitation of mitochondrial fusion, fission, and clearance accompanying increased quantities of mitochondria. SIGNIFICANCE: Treadmill exercise improved gait speed and balance, reduced oxidative stress, improved mitochondrial fusion and fission, increased mitochondrial amounts, and potentially attenuated dopaminergic neuron degeneration. Consequently, mitochondrial quality was improved in PD rats. PMID- 28986096 TI - High-fat diet enhances hepatic ischemia-reperfusion injury-induced apoptosis: Role of glucocorticoid receptors. AB - AIMS: The present study was designed to evaluate whether and how glucocorticoids can affect obesity-regulated hepatic ischemia-reperfusion (I/R) injury. MAIN METHODS: To this end, we first examined whether hydrocortisone (HCT) has protective effects on liver damage induced by hepatic I/R injury in mice receiving high fat diet treatment. We then explored the role of GR expression and phosphorylation in the anti-apoptotic effects of hydrocortisone upon hepatic I/R injury. KEY FINDINGS: We found that HCT reduced hepatic necrosis and inflammatory infiltration after hepatic I/R injury in mice that received high fat diet treatment. However, HCT lost the anti-apoptotic effects in high-fat diet treated mice. This phenomenon was associated with increased GRbeta expression, decreased basal levels of GR phosphorylation at Ser220 and lack of HCT-induced GR phosphorylation at Ser220 in high-fat diet treated mice. Additionally, basal levels of ERK phosphorylation was increased in high-fat diet treated mice, and I/R injury was associated with robustly increased ERK phosphorylation in high-fat diet treated mice, compared to normal diet treated mice. Furthermore, we demonstrated that high fat diet treated ERK1-/- mice exhibited robustly reduced apoptosis rate at 24h after reperfusion, compared to high fat diet treated wild type mice. Importantly, there was a decreased level of GRbeta after high fat diet treatment in ERK1-/- mice. SIGNIFICANCE: These results together suggested that ERK1 phosphorylation plays a critical role in regulating GRbeta expression and HCT-induce GR phosphorylation at Ser220, which is critical for the anti-apoptotic effects HCT on hepatic I/R injury. PMID- 28986097 TI - Effects of lentivirus-mediated ornithine decarboxylase gene on the proliferation and apoptosis of fibroblast-like synoviocytes in rats with arthritis. AB - OBJECTIVE: This study aimed to explore the effects of lentivirus-mediated ornithine decarboxylase (ODC) gene on the proliferation and apoptosis of fibroblast-like synoviocytes (FLSs) in rats with rheumatoid arthritis (RA). METHODS: Twenty Lewis rats were randomized into control group (ten rats without processing) and RA group (ten rats of adjuvant-induced arthritis). The third generation FLSs were randomized into test, control and blank groups. MTT assay and flow cytometry were employed to detect cell proliferation and apoptosis, respectively. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of tumor necrosis factor alpha (TNF-alpha), interferon-gamma (IFN-gamma), and interleukin-2 (IL-2). RESULTS: Lewis rats in the RA group became ill from 11days on and got seriously ill 18days after modeling. However, rats in the control group had no obvious change. MTT assay showed that the test group had higher cell proliferation than the blank and control groups (P1<0.001; P2<0.001). Flow cytometry revealed that the apoptosis of FLSs in the test group was significantly lower than that in the blank and control groups (P1<0.001; P2<0.001). ELISA showed that the test group had higher TNF-alpha, IFN-gamma and IL-2 level than the control and blank groups (all P<0.001), but no significant difference was found between the control and blank groups (all P>0.05). CONCLUSION: The results indicated that overexpression of ODC gene promotes the proliferation while suppressing apoptosis of FLSs in rats with RA. PMID- 28986098 TI - Reviewers' list December 2017. PMID- 28986099 TI - Downregulation of Pin1 in human atherosclerosis and its association with vascular smooth muscle cell senescence. AB - OBJECTIVE: Pin1 is prevalently overexpressed in human cancers and implicated to regulate cell growth and apoptosis. Thus far, however, no role for Pin1 has been described in modulating vascular smooth muscle cell (VSMC) senescence. METHODS: Immunohistochemistry and Western blotting were used to assess Pin1 protein level in human normal and atherosclerotic tissues. beta-galactosidase staining, cumulative population doubling level, telomerase activity, and relative telomere length measurement were used to confirm VSMC senescence. The expressions of Pin1 and other genes involved in this research were analyzed by quantitative reverse transcription polymerase chain reaction and Western blotting in VSMCs. Apolipoprotein E gene-deleted mice (ApoE-/-) fed a high-fat diet were treated with juglone or 10% ethanol, respectively, for 3 weeks. The extent of atherosclerosis was evaluated by Oil Red O, Masson trichrome staining, and immunohistology. RESULTS: Pin1 protein level decreased in human atherosclerotic tissues and VSMCs, synchronously with increased VSMC senescence. Adenoviral mediated Pin1 overexpression rescued cellular senescence in atherosclerotic VSMCs, with concurrent down-regulation of P53, p21, growth arrest and DNA-damage inducible protein 45-alpha (Gadd45a), phosphorylated retinoblastoma (p-pRb), p65 and upregulation of cyclin subfamilies (cyclin B, D, and E), and cyclin-dependent kinase subfamilies (2, 4, and 6), whereas Pin1 knockdown resulted in the converse effects, indicating that VSMC senescence mediated by Pin1 is an integrated response to diverse signals. In vivo data from ApoE-/- mice showed that treatment of juglone led to accelerated atherosclerosis development. CONCLUSIONS: Altogether this work supports a role for Pin1 as a vital modulator of VSMC senescence, thereby providing a novel target for regulation and control of atherosclerosis. PMID- 28986100 TI - Reduced shear stress and associated aortic deformation in the thoracic aorta of patients with chronic obstructive pulmonary disease. AB - OBJECTIVE: Central aortic stiffness and chronic obstructive pulmonary disease (COPD) are associated with increased incidence of devastating aortopathies. However, the exact mechanism leading to elevated aortic stiffness in patients with COPD is unknown. The purpose of this study was to quantify flow and shear hemodynamic indices, known markers of vascular remodeling, in the thoracic aorta of patients with mild to moderate COPD (n = 16) and to compare these results with an age-matched control group (n = 10). METHODS: Four-dimensional flow magnetic resonance imaging has been applied to measure hemodynamic wall shear stress (WSS) at four specific planes along the ascending aorta, aortic arch, and proximal descending aorta for all subjects. Peak systolic WSS and time-averaged WSS, which respectively reflect magnitude and temporal shear variability, were calculated at standardized planes. Aortic deformation was measured by means of relative area change (RAC) at the midlevel of the ascending and descending aorta. RESULTS: Compared with controls, patients with COPD had significantly reduced RAC in the mid ascending aorta (9% vs 18%; P < .0001) and descending aorta (15% vs 19%; P = .0206). Peak systolic WSS in COPD patients was significantly reduced in all considered planes, with the most dramatic difference occurring in the descending aorta (0.46 vs 0.86 N/m2; P < .0001). Peak systolic WSS and time-averaged WSS were both significantly correlated with aortic RAC at each evaluated plane. CONCLUSIONS: Reduced flow shear metrics assessed at specific aortic regions correlated with RAC, a marker of aortic stiffness. Reduced hemodynamic WSS may then contribute to central aortic stiffening and perpetuate the risk for development of severe aortopathy. PMID- 28986101 TI - The immature electrophysiological phenotype of iPSC-CMs still hampers in vitro drug screening: Special focus on IK1. AB - Preclinical drug screens are not based on human physiology, possibly complicating predictions on cardiotoxicity. Drug screening can be humanised with in vitro assays using human induced pluripotent stem cell-derived cardiomyocytes (iPSC CMs). However, in contrast to adult ventricular cardiomyocytes, iPSC-CMs beat spontaneously due to presence of the pacemaking current If and reduced densities of the hyperpolarising current IK1. In adult cardiomyocytes, IK1 finalises repolarisation by stabilising the resting membrane potential while also maintaining excitability. The reduced IK1 density contributes to proarrhythmic traits in iPSC-CMs, which leads to an electrophysiological phenotype that might bias drug responses. The proarrhythmic traits can be suppressed by increasing IK1 in a balanced manner. We systematically evaluated all studies that report strategies to mature iPSC-CMs and found that only few studies report IK1 current densities. Furthermore, these studies did not succeed in establishing sufficient IK1 levels as they either added too little or too much IK1. We conclude that reduced densities of IK1 remain a major flaw in iPSC-CMs, which hampers their use for in vitro drug screening. PMID- 28986102 TI - Reply to: "Herbal tea consumption and the liver - All is not what is seems!" PMID- 28986103 TI - The susceptibility of circulating human influenza viruses to tizoxanide, the active metabolite of nitazoxanide. AB - Nitazoxanide is a thiazolide compound that was originally developed as an anti parasitic agent, but has recently been repurposed for the treatment of influenza virus infections. Thought to exert its anti-influenza activity via the inhibition of hemagglutinin maturation and intracellular trafficking in infected cells, the effectiveness of nitazoxanide in treating patients with non-complicated influenza is currently being assessed in phase III clinical trials. Here, we describe the susceptibility of 210 seasonal influenza viruses to tizoxanide, the active circulating metabolite of nitazoxanide. An optimised cell culture-based focus reduction assay was used to determine the susceptibility of A(H1N1)pdm09, A(H3N2), and influenza B viruses circulating in the southern hemisphere from the period March 2014 to August 2016. Tizoxanide showed potent in vitro antiviral activity against all influenza viruses tested, including neuraminidase inhibitor resistant viruses, allowing the establishment of a baseline level of susceptibility for each subtype. Median EC50 values (+/-IQR) of 0.48 MUM (0.33 0.71), 0.62 MUM (0.56-0.75), 0.66 MUM (0.62-0.69), and 0.60 MUM (0.51-0.67) were obtained for A(H1N1)pdm09, A(H3N2), B(Victoria lineage), and B(Yamagata lineage) influenza viruses respectively. There was no significant difference in the median baseline tizoxanide susceptibility for each influenza subtype tested. This is the first report on the susceptibility of circulating viruses to tizoxanide. The focus reduction assay format described is sensitive, robust, and less laborious than traditional cell based antiviral assays, making it highly suitable for the surveillance of tizoxanide susceptibility in circulating seasonal influenza viruses. PMID- 28986104 TI - The effects of betulinic acid on neurobehavioral activity, electrophysiology and histological changes in an animal model of the Alzheimer's disease. AB - Alzheimer's disease (AD) is a common disorder characterized by aggregation and conversion of amyloid beta (Abeta) monomers to fibrils. Betulinic acid (BA) strongly accelerated this pathway through circumventing the oligomeric intermediate state. BA at doses of 0.2 and 0.4MUM/10MUl/rat (intra-hippocampal or i.h injection, vehicle: DMSO) was bilaterally administrated 180 and 10min before co-administration of Abeta (0.1MUM/5MUl/rat, i.h injection, vehicle: PBS) and Streptozotocin (STZ, 1.5mg/kg/10MUl/rat, intracerebroventricular or i.c.v. injection, vehicle: aCSF). The behavioral assessments (spatial and passive avoidance memory, anxiety, locomotion, depression, and motor coordination), electrophysiological evaluations (hippocampal long- term potentiation (LTP)) as well as histological changes were evaluated 30days after injections. The indices of spatial and passive avoidance memory, anxiety/depression and LTP records were significantly impaired in AD rats in comparison with the sham. Pretreatment of BA (0.4MUM) showed a more significant effect on memory, anxiety, all LTP parameters, and histological damage compared to a low dose in contrast to the AD group. Overall, BA pretreatment was able to prevent AD-induced neurobehavioral and LTP deficits in rats and the best effect was observed in molar ratio of 1:4 (Abeta to BA). PMID- 28986105 TI - Dynamic functional connectivity analysis reveals improved association between brain networks and eating behaviors compared to static analysis. AB - Uncontrollable eating behavior is highly associated with dysfunction in neurocognitive systems. We aimed to quantitatively link brain networks and eating behaviors based on dynamic functional connectivity analysis, which reflects temporal dynamics of brain networks. We used 62 resting-state functional magnetic resonance imaging data sets representing 31 healthy weight (HW) and 31 non-HW participants based on body mass index (BMI). Brain networks were defined using a data-driven group-independent component analysis and a dynamic connectivity analysis with a sliding window technique was applied. The network centrality parameters of the dynamic brain networks were extracted from each brain network and they were correlated to eating behavior and BMI scores. The network parameters of the executive control network showed a strong correlation with eating behavior and BMI scores only when a dynamic (p < 0.05), not static (p > 0.05), connectivity analysis was adopted. We demonstrated that dynamic connectivity analysis was more effective at linking brain networks and eating behaviors than static approach. We also confirmed that the executive control network was highly associated with eating behaviors. PMID- 28986106 TI - Tool-Driven Advances in Neuropeptide Research from a Nematode Parasite Perspective. AB - Expanding 'omics' datasets for parasitic nematodes have accelerated the identification of putative drug targets derived from the nematode nervous system. However, novel drug target validation is hampered by the absence of adequate localisation, functional characterisation, and receptor deorphanisation tools in key nematode pathogens. Reverse genetics techniques have advanced to encompass transgenic, targeted mutagenesis, gene silencing (RNA interference), and genome editing (CRISPR/Cas9) approaches in Caenorhabditis elegans. Unfortunately the translation to nematode pathogens has been slow, such that parasite-focused toolbox development and optimisation is critical. Here we review the discovery, localisation, and functional characterisation toolkit available for parasitic nematode neuropeptide research, and assess the scope and limitations of the tools and techniques for novel nematicide discovery. PMID- 28986107 TI - Parasites at Risk - Insights from an Endangered Marsupial. AB - Parasites are the most abundant form of life on earth and are vital components of ecosystem health. Yet, it is only relatively recently that attention has been given to the risks of extinction that parasites face when their hosts, particularly wildlife, are endangered. In such circumstances, parasites that are host-specific with complicated life cycles are most at risk. Such extinction/coextinction events have been poorly documented, principally because of the difficulties of following such extinction processes in nature. Fortunately, we were presented with the rare opportunity to catalogue an endangered Australian marsupial's parasites; we present our near-complete catalogue here. We incorporate this catalogue into a predictive framework to understand which parasites might be most vulnerable to coextinction, which we hope will serve as a model for endangered hosts and their parasites elsewhere. PMID- 28986108 TI - Temporal case-based reasoning for type 1 diabetes mellitus bolus insulin decision support. AB - Individuals with type 1 diabetes have to monitor their blood glucose levels, determine the quantity of insulin required to achieve optimal glycaemic control and administer it themselves subcutaneously, multiple times per day. To help with this process bolus calculators have been developed that suggest the appropriate dose. However these calculators do not automatically adapt to the specific circumstances of an individual and require fine-tuning of parameters, a process that often requires the input of an expert. To overcome the limitations of the traditional methods this paper proposes the use of an artificial intelligence technique, case-based reasoning, to personalise the bolus calculation. A novel aspect of our approach is the use of temporal sequences to take into account preceding events when recommending the bolus insulin doses rather than looking at events in isolation. The in silico results described in this paper show that given the initial conditions of the patient, the temporal retrieval algorithm identifies the most suitable case for reuse. Additionally through insulin-on board adaptation and postprandial revision, the approach is able to learn and improve bolus predictions, reducing the blood glucose risk index by up to 27% after three revisions of a bolus solution. PMID- 28986109 TI - X protein variants of the autochthonous Latin American hepatitis B virus F genotype promotes human hepatocyte death by the induction of apoptosis and autophagy. AB - The hepatitis B virus X protein (HBV-X) is a multifunctional regulatory protein associated with the pathogenesis of liver disease in chronic HBV infection. Basal core promoter mutations (BCP), associated with the clinical course of chronic HBV infection, affect HBV-X at 130-131 positions. The role of these mutations on HBV X biological activity remains largely unknown. The aim of this study was to analyze the impact of the presence of different amino acids at 130-131 positions of HBV-X on the biological activity of the protein. Transient expression of wild type and mutant F1b and F4 HBV-X increased cell mortality by the induction of apoptosis in human hepatoma cells. The wild type and mutant HBV-X differentially modulate the expression of pro-apoptotic (Bax) and anti-apoptotic (Bcl-2 and Bcl X) regulatory proteins of the Bcl-2 family. Furthermore, the expression of HBV-X variants of both subgenotypes induced autophagy of human tumoral hepatocytes. In conclusion, HBV-X variants of the Latin American HBV F genotype promotes human hepatocytes death by the induction of apoptosis and autophagy. The results of this work describe some of the molecular mechanisms by which HBV-X variants contribute to the pathogenesis of liver diseases in the infected liver and help to the biological characterization of genotype F, responsible of the majority of HBV infections in Argentina. PMID- 28986110 TI - The Gulfwatch contaminants monitoring program in the Gulf of Maine: Are its data being used for ocean protection, with special reference to Nova Scotia, Canada? AB - The Gulfwatch Contaminants Monitoring Program is part of the Canada-US, Gulf of Maine Council on the Marine Environment (GOMC). Programs monitoring legacy toxic substances, i.e., chemical contaminants, such as Gulfwatch, collect and analyse environmental samples (e.g., blue mussels), interpret the data, and report on chemical levels and trends (spatial and temporal) in coastal waters. This study explored the extent to which its extensive information (data, reports, papers) has been used broadly and by Nova Scotia, a GOMC member. A mixed-methods study was conducted, using quantitative and qualitative metrics. Citations to some Gulfwatch papers and analysis of use of the Gulfwatch website showed that its data and information were accessed, mostly by government departments. However, interviews revealed that the departments were not using the data to inform Nova Scotia provincial coastal policy or practices. Recommendations are presented to improve the visibility and use of information provided by long-term, environmental monitoring programs. PMID- 28986111 TI - Subsurface low dissolved oxygen occurred at fresh- and saline-water intersection of the Pearl River estuary during the summer period. AB - Estuarine oxygen depletion is one of the worldwide problems, which is caused by the freshwater-input-derived severe stratification and high nutrients loading. In this study we presented the horizontal and vertical distributions of dissolved oxygen (DO) in the Pearl River estuary, together with temperature, salinity, chlorophyll a concentration and heterotrophic bacteria abundance obtained from two cruises during the summer (wet) and winter (dry) periods of 2015. In surface water, the DO level in the summer period was lower and varied greater, as compared to the winter period. The DO remained unsaturated in the summer period if salinity is <12 and saturated if salinity is >12; while in the winter period it remained saturated throughout the estuary. In subsurface (>5m) water, the DO level varied from 0.71 to 6.65mgL-1 and from 6.58 to 8.20mgL-1 in the summer and winter periods, respectively. Particularly, we observed an area of ~1500km2 low DO zone in the subsurface water with a threshold of 4mgDOL-1 during this summer period, that located at the fresh- and saline-water intersection where is characterized with severe stratification and high heterotrophic bacteria abundance. In addition, our results indicate that spatial DO variability in surface water was contributed differently by biological and physio-chemical variables in the summer and winter periods, respectively. PMID- 28986112 TI - Seagrass leaf element content: A global overview. AB - Knowledge on the role of seagrass leaf elements and in particular micronutrients and their ranges is limited. We present a global database, consisting of 1126 unique leaf values for ten elements, obtained from literature and unpublished data, spanning 25 different seagrass species from 28 countries. The overall order of average element values in seagrass leaves was Na>K>Ca>Mg>S>Fe>Al>Si>Mn>Zn. Although we observed differences in leaf element content between seagrass families, high intraspecific variation indicated that leaf element content was more strongly determined by environmental factors than by evolutionary history. Early successional species had high leaf Al and Fe content. In addition, seagrass leaf element content also showed correlations with macronutrients (N and P), indicating that productivity also depends on other elements. Expected genomes of additional seagrass species in combination with experiments manipulating (micro)nutrients and environmental drivers might enable us to unravel the importance of various elements to sustain productive and flourishing meadows. PMID- 28986113 TI - Water quality near Estonian harbours in the Baltic Sea as observed from entire MERIS full resolution archive. AB - Variations and trends in water quality parameters (total suspended matter and coloured dissolved organic matter) were examined in five harbours in the eastern Baltic Sea using satellite imagery collected from 2002 to 2011 by the Medium Resolution Imaging Spectrometer (MERIS) at full spatial resolution (300*300m). In the eastern Gulf of Finland harbours (Sillamae, Kunda) the TSM monthly variations were related to monthly mean wind speed. In Tallinn harbour, which operates >6000 vessels annually, evidence of anthropogenic impacts was identified through inter annual TSM variations. The vessel traffic footprint was ascertained from the significant correlation (R=0.66; p=0.035) between the number of annual vessel visits and mean annual TSM concentration. In the harbour of Parnu, located close to the river mouth, inter-annual water quality variations in terms of the CDOM concentrations were affected by the mean annual river discharge levels of the Parnu River. PMID- 28986114 TI - Synthesis of photocaged 6-O-(2-nitrobenzyl)guanosine and 4-O-(2-nitrobenzyl) uridine triphosphates for photocontrol of the RNA transcription reaction. AB - 6-O-(2-Nitrobenzyl)guanosine and 4-O-(2-nitrobenzyl)uridine triphosphates (NBGTP, NBUTP) were synthesized, and their biochemical and photophysical properties were evaluated. We synthesized NBUTP using the canonical triphosphate synthesis method and NBGTP from 2',3'-O-TBDMS guanosine via a triphosphate synthesis method by utilizing mild acidic desilylation conditions. Deprotection of the nitrobenzyl group in NBGTP and NBUTP proceeded within 60s by UV irradiation at 365nm. Experiments using NBGTP or NBUTP in T7-RNA transcription reactions showed that NBGTP could be useful for the photocontrol of transcription by UV irradiation. PMID- 28986115 TI - A 'catch and release' strategy towards HPLC-free purification of synthetic oligonucleotides by a combination of the strain-promoted alkyne-azide cycloaddition and the photocleavage. AB - A convenient strategy to purify oligonucleotides (ONs) synthesized by solid phase synthesis on an automatic DNA/RNA synthesizer was described. By attaching a photocleavable azide linker as the last phosphoramidite unit in the ON synthesis, only the desired full-length sequence was 'caught' on a controlled pore glass (CPG) resin possessing an aza-dimethoxycyclooctyne (DIBAC) derivative. Washing the resulting CPG resin to remove all unbounded species, the subsequent photoirradiation allowed the pure ONs to be 'released' without leaving any chemical modifications on native ON structure or chemical reagents from the solid phase ON synthesis. PMID- 28986116 TI - 9-Substituted acridine derivatives as acetylcholinesterase and butyrylcholinesterase inhibitors possessing antioxidant activity for Alzheimer's disease treatment. AB - We investigated the inhibitory activity of 4 groups of novel acridine derivatives against acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and carboxylesterase (CaE) using the methods of enzyme kinetics and molecular docking. Antioxidant activity of the compounds was determined using the 2,2' azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+) radical decolorization assay as their ability to scavenge free radicals. Analysis of the esterase profiles and antiradical activities of the acridine derivatives showed that 9 aryl(heteroaryl)-N-methyl-9,10-dihydroacridines have a high radical-scavenging activity but low potency as AChE and BChE inhibitors, whereas 9-aryl(heteroaryl) N-methyl-acridinium tetrafluoroborates effectively inhibit cholinesterases but do not exhibit antiradical activity. In contrast, a group of derivatives of 9 heterocyclic amino-N-methyl-9,10-dihydroacridine has been found that combine effective inhibition of AChE and BChE with rather high radical-scavenging activity. The results of molecular docking well explain the observed features in the efficacy, selectivity, and mechanism of cholinesterase inhibition by the acridine derivatives. Thus, in a series of acridine derivatives we have found compounds possessing dual properties of effective and selective cholinesterase inhibition together with free radical scavenging, which makes promising the use of the acridine scaffold to create multifunctional drugs for the therapy of neurodegenerative diseases. PMID- 28986117 TI - Screening, prophylaxis and counselling before the start of biological therapies: A practical approach focused on IBD patients. AB - : The standard of care in the management of immune-mediated inflammatory conditions relies on immunomodulators, glucocorticoids, and biologicals (including anti-tumour necrosis factor -alpha and other monoclonal antibodies). These agents have an overall favourable benefit/risk ratio; however, they modulate the immune response as part of their mechanisms of action, and therefore they may increase the risk of developing infections, particularly in older patients or in patients with concomitant corticosteroids. Some of these infections may be preventable by immunization, chemoprophylaxis or counselling. AIM: screening for and monitoring infections throughout these therapies is so mandatory to ensure patients' safety. Still, standardized guidelines focused on these procedures have yet to be established. This review aims to fill such a gap. The authors searched for articles published in English from 2009 until 2017 using PUBMED, with the terms "immunomodulators", "biological drugs", "anti-TNF alpha", "inflammatory bowel diseases", "immunomediated inflammatory diseases", "risk of infection", "infection prevention", "screening", "immunization", "tuberculosis", "latent tuberculosis", "listeriosis", "endemic mycosis", "Pneumocystis jiroveci pneumonia", "granulomatous infection", "varicella", "herpes virus", "hepatitis B", "hepatitis A", "hepatitis C" and identified the journal articles. Based on the literature and in their own experience the authors established recommendations and a practical guide for infections' screening, monitoring and prevention before and during immunomodulatory and biological therapies. PMID- 28986118 TI - Full-thickness skin grafts for lower leg defects coverage: Interest of postoperative immobilization. AB - INTRODUCTION: Full-thickness skin graft is an effective reconstruction method after excision of skin lesions on the lower limb that are not amenable to primary closure. The randomness of graft take is the major drawback of this procedure. OBJECTIVE: The objective of the study was to evaluate the outcome of full thickness skin grafts (FTSG), used to repair lower leg defects after excision of skin lesions, after a 5-day immobilization period. MATERIAL AND METHODS: All consecutive patients who underwent FTSG to cover defects below the knee between November 2011 and January 2016 were retrospective reviewed. Graft take was assessed and defined as good (>90% graft take), moderate (between 50% and 90% graft take), or poor (<50% graft take). RESULTS: Seventy patients were included. Median age was 70 years (range, 18-92 years). The median area of the defect was 12cm2. Graft take was good in 64 patients (91.4%), moderate in 3 patients (4.3%), and poor in 3 patients (4.3%) at Day 5. Complications included hematoma (11%), infection (14%) and venous thrombosis (3%). CONCLUSION: Full-thickness skin graft is a reliable method to repair defects on the lower leg after removal of skin lesions. A 5-day immobilization period can improve the graft take. The authors have indicated no significant interest with commercial supporters. PMID- 28986119 TI - Utility of Risk Stratification for Paclitaxel Hypersensitivity Reactions. AB - BACKGROUND: Hypersensitivity reactions (HSRs) are a common impediment to paclitaxel therapy. Management strategies to guide care after a paclitaxel induced HSR are needed. OBJECTIVE: The objective was to evaluate the utility and safety of risk stratification on the basis of severity of the initial HSR. METHODS: A risk stratification pathway was developed on the basis of a retrospective review of the management and outcome of 130 patients with paclitaxel-induced HSRs at Massachusetts General Hospital. This pathway was then studied prospectively in patients referred to Allergy/Immunology with paclitaxel induced HSRs. RESULTS: The study population (n = 35) had a mean age of 56.1 +/- 12 years and most were women (n = 33 [94%]). All 5 patients (15%) with grade 1 initial HSRs were successfully reexposed to paclitaxel, 1 patient at the standard infusion rate and 4 patients at 50% of the standard infusion rate. Thirty patients (85%) with grade 2 to 4 initial HSRs underwent initial paclitaxel desensitization based on the risk stratification pathway. No patients developed severe HSRs using the pathway. Eleven (31%) patients had HSRs that were mild to moderate in nature (grade 1, n = 4 [11%]; grade 2, n = 6 [17%]; grade 3, n = 1 [3%]) during their first desensitization. Sixteen (46%) of the 35 patients safely returned to the outpatient infusion setting for paclitaxel treatment at 50% of the standard infusion rate. Seven (20%) discontinued paclitaxel before the completion of the risk stratification pathway because of disease progression, completion of therapy, or death. CONCLUSIONS: A management strategy using the initial HSR severity for risk stratification allowed patients to receive paclitaxel safely. PMID- 28986120 TI - Acetyl Salicylic Acid Challenge in Children with Hypersensitivity Reactions to Nonsteroidal Anti-Inflammatory Drugs Differentiates Between Cross-Intolerant and Selective Responders. AB - BACKGROUND: Hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) in children are becoming a great concern. Most studies have focused on adults, with noted discrepancies observed in the classification of hypersensitivity reactions to NSAIDs in children when compared with adults. OBJECTIVE: To phenotype a group of children with hypersensitivity reactions to NSAIDs, including paracetamol, and analyze the degree of agreement with the entities reported in adults and how they fit the proposed classifications. METHODS: The study comprised 116 children aged 0.5 to 14 years, with a clinical history indicative of hypersensitivity reactions to NSAIDs. They all underwent a single-blind oral provocation test with acetyl salicylic acid, except in those cases when this was the suspected drug, in which case the challenge was done first with ibuprofen. If positive, cross-intolerance was established and if negative, an oral provocation test with the culprit drug was performed to establish a selective response or exclude allergy. RESULTS: Of the 26% diagnosed as hypersensitive to NSAIDs, 83% were cross-intolerant and 17% selective reactors. The highest significant differences between reactors and nonreactors were observed in the time to reaction after drug intake and the clinical entity (P < .0001), followed by drug involved and age (P < .01). CONCLUSIONS: From the total number of cases confirmed with NSAID hypersensitivity, 83% were cross intolerant. In cross-intolerant reactions, both cutaneous and respiratory manifestations are common. Acetyl salicylic acid challenge as the first approach proved to be safe and useful to establish the diagnosis. PMID- 28986122 TI - Mitochondrial ROS-mediated post-transcriptional regulation of alpha-synuclein through miR-7 and miR-153. AB - Dysregulation of human alpha-synuclein (alpha-SYN) is one of the major contributors in the pathogenesis of Parkinson's disease. 1-methyl-4 phenylpyridinium (MPP+) is well known neurotoxin which increases alpha-SYN expression and causes dopaminergic neuronal death. Increasing evidence suggests microRNAs (miRNAs), especially miRNA-7 and miR-153, have important role in the regulation of alpha-SYN translation and they can prevent MPP+-mediated neuronal death. Here, we examined whether MPP+-mediated upregulation of alpha-SYN expression is directly related to miRNA-7 and miR-153. First, we established HEK293/TR cells stably expressing both miR-7 and miR-153. Human alpha-SYN 3'-UTR containing target sites for both miRNAs was cloned next to a luciferase reporter construct. To control the total levels of reporter mRNA, a tetracycline-inducible system was used. Compared to wild-type HEK293/TR cells, cells overexpressing both miRNAs demonstrated about 75% reduction in luciferase activity. MPP+ treatment, however, significantly increased luciferase activity of human alpha-SYN 3'-UTR. Either quenching mitochondrial reactive oxygen species (ROS) or translational inhibition significantly reduced MPP+-mediated luciferase activity, suggesting mitochondrial ROS is responsible for MPP+-induced alpha-SYN translation. Together, our results suggest that MPP+-mediated increased alpha-SYN levels are contributed by mitochondrial ROS-mediated de novo protein synthesis which is regulated by miRNA-7 and miR-153. PMID- 28986121 TI - A cellular threshold for active ERK1/2 levels determines Raf/MEK/ERK-mediated growth arrest versus death responses. AB - In addition to its conventional role for cell proliferation and survival, the Raf/MEK/Extracellular signal-regulated kinase (ERK) pathway can also induce growth arrest and death responses, if aberrantly activated. Here, we determined a molecular basis of ERK1/2 signaling that underlies these growth inhibitory physiological outputs. We found that overexpression of ERK1 or ERK2 switches DeltaRaf-1:ER-induced growth arrest responses to caspase-dependent apoptotic death responses in different cell types. These death responses, however, were reverted to growth arrest responses upon titration of cellular phospho-ERK1/2 levels by the MEK1/2 inhibitor AZD6244. These data suggest that a cellular threshold for active ERK1/2 levels exists and affects the cell fate between death and growth arrest. We also found that death-mediating ability of ERK2 is abolished by the catalytic site-disabling Lys52Arg replacement or significantly attenuated by the F-site recruitment site-disabling Tyr261Asn replacement, although unaffected by the mutations that disable the common docking groove or the dimerization interface. Therefore, ERK1/2 mediates death signaling dependently of kinase activity and specific physical interactions. Intriguingly, Tyr261Asn-replaced ERK2 could still mediate growth arrest signaling, further contrasting the molecular basis of ERK1/2-mediated growth arrest and death signaling. These data reveal a mechanism underlying the role of ERK1/2 as a focal point of Raf/MEK/ERK-mediated growth arrest and death signaling. PMID- 28986123 TI - Possible anti-depressant effect of efavirenz and pro-depressive-like effect of voriconazole in specified doses in various experimental models of depression in mice. AB - BACKGROUND: Reports from experimental and clinical studies have indicated the possible relation between cholesterol and depression. Efavirenz (EFV) and Voriconazole (VRC) have been reported to affect cholesterol-24S-hydroxylase enzyme. The objective of the present study was to evaluate the effect of EFV and VRC in experimental models of depression in mice. METHODS: There was a measurement of immobility time in forced swim test and tail suspension test in which mice were previously subjected to the treatment of EFV (0.09mg/kg, orally (po)) and VRC (75mg/kg, intraperitoneally (ip)) separately for 14days. Sucrose intake was measured during stress schedule of 21days in chronic mild stress model in which mice were subjected to above mentioned drug treatment for last 14days. There was an estimation of serum total cholesterol and brain serotonin levels on day 21. RESULTS: The results indicated that mice treated with EFV showed a significant decrease in the immobility time and increase in sucrose intake with decrease in serum total cholesterol. Mice treated with VRC showed a significant increase in the immobility time and decrease in the sucrose intake with increase in serum total cholesterol. There was a significant increase and decrease in brain serotonin levels in mice treated with EFV and VRC respectively. CONCLUSION: The results of the present study indicates the possible anti-depressant effect of EFV and pro-depressive-like effect of VRC in specified doses in mice, raising the possibility that stimulation but not inhibition of cholesterol-24S-hydroxylase may be important in the treatment of depression. PMID- 28986124 TI - Real-world health care utilization and effectiveness of omalizumab for the treatment of severe asthma. AB - BACKGROUND: Omalizumab is indicated for the treatment of moderate to severe asthma. There is limited observational evidence on the costs and effectiveness of omalizumab. OBJECTIVE: To examine the costs and effectiveness of omalizumab for treatment of severe asthma relative to nonusers. METHODS: We conducted a within person repeated-measures matched cohort study in Ontario, Canada from April 1, 2012 to March 31, 2014. Continuous users of omalizumab were matched with up to 4 nonusers according to age, sex, recent specialist visits, oral corticosteroid use, asthma severity, and Charlson comorbidity score. The primary outcome was direct health care costs. Secondary outcomes were asthma-related hospitalizations or emergency department visits and oral corticosteroid use. The association between omalizumab use and each outcome was assessed using mixed-effects models adjusting for confounders. RESULTS: Ninety-five omalizumab users and 352 nonusers were matched. Among users, there was a significant increase in health care costs of $1,796 per person owing to the cost of the medication at treatment initiation (P < .0001). Costs did not change significantly among nonusers ($85 increase in average monthly costs per person; P = .59). We found no significant changes in the rates of asthma-related hospitalizations or emergency department visits among omalizumab users (P = .44) or nonusers (P = .99) between pre- and postintervention periods. CONCLUSION: The use of omalizumab was associated with increased costs but no evidence of lower rates of clinically important outcomes. These results suggest omalizumab had limited effectiveness in our study population. Future studies should further explore subsets of patients most likely to benefit from omalizumab therapy. PMID- 28986125 TI - Biliary stenosis after transjugular intrahepatic portosystemic shunt. PMID- 28986126 TI - The evolution of asymmetric photosensitive structures in metazoans and the Nodal connection. AB - Asymmetries are observed in a great number of taxa in metazoans. More particularly, functional lateralization and neuroanatomical asymmetries within the central nervous system have been a matter of intense research for at least two hundred years. While asymmetries of some paired structures/organs (e.g. eyes, ears, kidneys, legs, arms) constitute random deviations from a pure bilateral symmetry, brain asymmetries such as those observed in the cortex and epithalamus are directional. This means that molecular and anatomical features located on one side of a given structure are observed in most individuals. For instance, in humans, the neuronal tract connecting the language areas is enlarged in the left hemisphere. When asymmetries are fixed, their molecular mechanisms can be studied using mutants displaying different phenotypes: left or right isomerism of the structure, reversed asymmetry or random asymmetry. Our understanding of asymmetry in the nervous system has been widely enriched thanks to the characterization of mutants affecting epithalamus asymmetry. Furthermore, two decades ago, pioneering studies revealed that a specific morphogen, Nodal, active only on one side of the embryo during development is an important molecule in asymmetry patterning. In this review, I have gathered important data bringing insight into the origin and evolution of epithalamus asymmetry and the role of Nodal in metazoans. After a short introduction on brain asymmetries (chapter I), I secondly focus on the molecular and anatomical characteristics of the epithalamus in vertebrates and explore some functional aspects such as its photosensitive ability related to the pineal complex (chapter II). Third, I discuss homology relationship of the parapineal organ among vertebrates (chapter III). Fourth, I discuss the possible origin of the epithalamus, presenting cells displaying photosensitive properties and/or asymmetry in the anterior part of the body in non-vertebrates (chapter IV). Finally, I report Nodal signaling expression data and functional experiments performed in different metazoan groups (chapter V). PMID- 28986127 TI - Vitamin D and asthma: a case to answer. PMID- 28986129 TI - Validation of the Italian version of the UNESP-Botucatu unidimensional composite pain scale for the assessment of postoperative pain in cattle. AB - OBJECTIVE: The aim of this study was to validate the Italian version of the UNESP Botucatu Unidimensional Composite Pain Scale (UCPS-IV) for assessing postoperative pain in cattle. STUDY DESIGN: Video analysis and psychometric testing. ANIMALS: A total of 40 Nellore cattle, age 2-3 years, weighing 365+/-51 kg. METHODS: An English version of the scale was translated to Italian and back translated to English to ensure semantic equivalence. A total of four Italian observers and the researcher who developed the original scale (considered as the gold standard) analysed videos of 40 cattle previously subjected to orchiectomy (recorded for each cattle at four predetermined timepoints during the perioperative period) unaware of the videos' timepoint. They assigned a pain score [ranging from no pain (0) to severe pain (10)] using the Italian version of the scale and verified the need for analgesic treatment for each animal. The obtained scores were subjected to psychometric validity, responsiveness and reliability tests. RESULTS: The factor analysis of the scale resulted in a one factor solution. Significant changes in pain scores in response to surgery and analgesics confirmed not only the content and construct validity, but also responsiveness. The agreement between the researcher who developed the original scale and the blinded observers and the correlation between the pain scores determined by the scale and those determined by three classical unidimensional pain scales confirmed criterion and concurrent validity. Internal consistency of the scale was excellent. Inter- and intrarater reliability ranged from moderate to good and from moderate to very good for all scale items, respectively, supporting reproducibility and stability. The cut-off point for rescue analgesia calculated by the receiver operating characteristic curve was > 3. CONCLUSIONS AND CLINICAL RELEVANCE: The results confirm that the UNESP-Botucatu UCPS-IV appears to be a valid and reliable tool for the assessment of postorchiectomy pain in the bovine species. The determination of a cut-off point for rescue analgesia is also helpful for guiding analgesic therapy. PMID- 28986128 TI - Vitamin D supplementation to prevent asthma exacerbations: a systematic review and meta-analysis of individual participant data. AB - BACKGROUND: A previous aggregate data meta-analysis of randomised controlled trials showed that vitamin D supplementation reduces the rate of asthma exacerbations requiring treatment with systemic corticosteroids. Whether this effect is restricted to patients with low baseline vitamin D status is unknown. METHODS: For this systematic review and one-step and two-step meta-analysis of individual participant data, we searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science for double-blind, placebo controlled, randomised controlled trials of vitamin D3 or vitamin D2 supplementation in people with asthma that reported incidence of asthma exacerbation, published between database inception and Oct 26, 2016. We analysed individual participant data requested from the principal investigator for each eligible trial, adjusting for age and sex, and clustering by study. The primary outcome was the incidence of asthma exacerbation requiring treatment with systemic corticosteroids. Mixed-effects regression models were used to obtain the pooled intervention effect with a 95% CI. Subgroup analyses were done to determine whether effects of vitamin D on risk of asthma exacerbation varied according to baseline 25-hydroxyvitamin D (25[OH]D) concentration, age, ethnic or racial origin, body-mass index, vitamin D dosing regimen, use of inhaled corticosteroids, or end-study 25(OH)D levels; post-hoc subgroup analyses were done according to sex and study duration. This study was registered with PROSPERO, number CRD42014013953. FINDINGS: Our search identified 483 unique studies, eight of which were eligible randomised controlled trials (total 1078 participants). We sought individual participant data for each and obtained it for seven studies (955 participants). Vitamin D supplementation reduced the rate of asthma exacerbation requiring treatment with systemic corticosteroids among all participants (adjusted incidence rate ratio [aIRR] 0.74, 95% CI 0.56-0.97; p=0.03; 955 participants in seven studies; high-quality evidence). There were no significant differences between vitamin D and placebo in the proportion of participants with at least one exacerbation or time to first exacerbation. Subgroup analyses of the rate of asthma exacerbations treated with systemic corticosteroids revealed that protective effects were seen in participants with baseline 25(OH)D of less than 25 nmol/L (aIRR 0.33, 0.11-0.98; p=0.046; 92 participants in three studies; moderate-quality evidence) but not in participants with higher baseline 25(OH)D levels (aIRR 0.77, 0.58-1.03; p=0.08; 764 participants in six studies; moderate-quality evidence; pinteraction=0.25). p values for interaction for all other subgroup analyses were also higher than 0.05; therefore, we did not show that the effects of this intervention are stronger in any one subgroup than in another. Six studies were assessed as being at low risk of bias, and one was assessed as being at unclear risk of bias. The two-step meta-analysis did not reveal evidence of heterogeneity of effect (I2=0.0, p=0.56). INTERPRETATION: Vitamin D supplementation reduced the rate of asthma exacerbations requiring treatment with systemic corticosteroids overall. We did not find definitive evidence that effects of this intervention differed across subgroups of patients. FUNDING: Health Technology Assessment Program, National Institute for Health Research (reference number 13/03/25). PMID- 28986130 TI - Covalent binding design strategy: A prospective method for discovery of potent targeted anticancer agents. AB - Cancer remains the most serious disease that threatens human health. Molecularly targeted cancer therapies, specifically small-molecule protein kinase inhibitors, form an important part of cancer therapy. Targeted covalent modification represents a proven approach to drug discovery with the recent FDA approvals of afatanib, ibrutinib, and osimertinib agents, which were designed to undergo an irreversible hetero-Michael addition reaction with a unique cysteine residue of a specific protein. Covalent inhibitors possess numerous advantages, including increased biochemical efficacy, longer duration of action, the high potential for improved therapeutic index due to lower effective dose, and the potential to inhibit certain drug resistance mechanisms. In this regard, the novel targeted anticancer agents whose activity is presumably dependent upon a hetero-Michael addition reaction with thiols are summarized in this article. PMID- 28986132 TI - New perspectives in cancer: Modulation of lipid metabolism and inflammation resolution. AB - Inflammation is considered an enabling feature of cancer. Besides the persistence of inflammatory stimuli, also defective mechanisms of resolution can lead to chronic inflammation. Inflammation resolution is an active process controlled by lipidic specialized pro-resolving mediators (SPMs), derived from omega-3 or omega 6 essential polyunsaturated fatty acids (PUFA) through the activity of lipoxygenases (ALOX5 and 15). Thus, a lack or defect in resolution mechanisms may affect cancer development and progression by prolonging inflammation. Components of pro-resolving pathways (PUFA, enzymes, or SPMs) have been reported to modulate various cancer features by affecting both cancer cells and cancer-associated stroma. Here, we will review the most important mechanisms by which SPMs, omega 3/6 PUFA, and ALOXs affect cancer biology, paying particular attention to their role in the inhibition of inflammation and angiogenesis, two of the most important hallmarks of cancer. The collection of these results may suggest novel perspectives in cancer management based on the modulation of lipid metabolism and the production of SPMs. PMID- 28986131 TI - Selenoprotein MsrB1 deficiency exacerbates acetaminophen-induced hepatotoxicity via increased oxidative damage. AB - Acetaminophen (APAP) overdose induces acute liver damage and failure via reactive oxygen species production and glutathione (GSH) depletion. Methionine sulfoxide reductase B1 (MsrB1) is an antioxidant selenoenzyme that specifically catalyzes the reduction of methionine R-sulfoxide residues. In this study, we used MsrB1 gene-knockout mice and primary hepatocytes to investigate the effect of MsrB1 on APAP-induced hepatotoxicity. Analyses of histological alterations and serum indicators of liver damage showed that MsrB1-/- mice were more susceptible to APAP-induced acute liver injury than wild-type (MsrB1+/+) mice. Consistent with the in vivo results, primary MsrB1-/- hepatocytes displayed higher susceptibility to APAP-induced cytotoxicity than MsrB1+/+ cells. MsrB1 deficiency increased hepatic oxidative stress after APAP challenge such as hydrogen peroxide production, lipid peroxidation, and protein oxidation levels. Additionally, basal and APAP-induced ratios of reduced-to-oxidized GSH (GSH/GSSG) were significantly lower in MsrB1-/- than in MsrB1+/+ livers. Nrf2 nuclear accumulation and heme oxygenase-1 expression levels after APAP challenge were lower in MsrB1-/- than in MsrB1+/+ livers, suggesting that MsrB1 deficiency attenuates the APAP-induced activation of Nrf2. Collectively, the results of this study suggest that selenoprotein MsrB1 plays a protective role against APAP-induced hepatotoxicity via its antioxidative function. PMID- 28986133 TI - Glycated albumin predicts the development of early diabetic nephropathy in patients with type 2 diabetes. PMID- 28986134 TI - Consequences of adding gum Arabic as a cryoprotectant on motility and viability of frozen stallion semen. AB - A trial was conducted to check effect of adding gum Arabic (GA) instead of egg yolk (EY) as a cryoprotectant for stallion sperm. Two experiments were designed; experiment I tested adding 3 levels of nonheated GA (i.e., 3, 6 and 9 g/100 mL diluents) in HF-20 extender. However, in experiment II the same levels were tested except that GA was heated at 80 degrees C for 60 min. HF-20 containing 10% of EY was used as control. In experiment I, sperm frozen in HF-20 containing nonheated GA exhibited lower percentages of motile sperm, progressively motile sperm and sperm with intact plasma membranes, vitality rate, and acrosome integrity after cooling or after deep freezing. Frozen semen in HF-20 containing 3-6% of preheated GA in experiment II maintained sperm motility at 46-50% and elevated progressive motility at 27%. The semen diluted in preheated GA (6%) and frozen exhibited a fertility rate of 40% (2/5). A similar fertility rate (40%) was found in the control semen (i.e. 10%) compared to those that were inseminated with frozen semen in preheated 3% GA (20%, 1/5). These results suggest that preheated GA could be used as an alternative cryoprotectant for cryopreserving stallion sperm. PMID- 28986135 TI - Impact of supplementation of semen extender with antioxidants on the quality of chilled or cryopreserved Arabian stallion spermatozoa. AB - The aim of the present study was to evaluate the effects of supplementation of semen extender with various non-enzymatic antioxidants on the quality of cooled or cryopreserved Arabian stallion spermatozoa. Semen collected from four pure Arabian stallions was centrifuged at 600g for 15 min. Spermatozoa were then diluted in INRA-82 extender supplemented with bovine serum albumin (BSA; 0, 10, 15 and 20 mg/mL) or trehalose (0, 75, 100 and 150 mM) or zinc sulphate (0, 100, 150 and 200 MUM). The diluted semen was then either cooled at 5 degrees C or cryopreserved in 0.5-ml plastic straws. After cooling or thawing, sperm motility, viability, sperm abnormalities, viability index, and plasma membrane integrity were evaluated. The results showed that supplementation of semen extender with 150 mM trehalose or with 200 MUM zinc sulphate significantly (P < 0.05) improved motility, viability, sperm membrane integrity and acrosome status in Arabian stallion spermatozoa after cooling or after freezing and thawing compared with controls (non-supplemented media) or with those supplemented with other concentrations of trehalose or zinc sulphate. Supplementation of semen extender with BSA did not improve sperm motility or cryosurvival of Arabian stallion spermatozoa after cooling or after freezing and thawing. In conclusion, supplementation of semen extender with non-enzymatic antioxidants (trehalose or zinc sulphate) improved the quality of chilled and frozen/thawed Arabian stallion spermatozoa. The most beneficial effects occur when semen diluent was supplemented with 150 mM trehalose or 200 MUM zinc sulphate. PMID- 28986136 TI - 'Corrigendum to "Severe hepatitis under combined immunotherapy: Resolution under corticosteroids plus anti-thymocyte immunoglobulins" [Eur J Cancer 81 (August 2017) 203-205]'. PMID- 28986137 TI - Immediate completion lymph node dissection in stage IIIA melanoma does not provide significant additional staging information beyond EORTC SN tumour burden criteria. PMID- 28986138 TI - HDL functionality in familial hypercholesterolemia: effects of treatment modalities and pharmacological interventions. AB - Recent studies have demonstrated that assessment of high-density lipoprotein (HDL) functionality indices, instead of HDL cholesterol measurement, is a more robust tool for the evaluation of the functional status of HDL and cardiovascular risk. There are qualitative abnormalities of HDL particles in familial hypercholesterolemia (FH) patients that might represent potential therapeutic targets. Despite the potential promise of optimizing HDL functionality for the treatment of FH, there has been no prior comprehensive review focusing on the impact of different lipid-modifying therapies on HDL functionality in FH patients. In the present review, we aim to fulfill this gap and provide a concise summary on the impact of different lipid-modifying therapies on HDL functionality in FH. PMID- 28986140 TI - Barriers to and facilitators of independent non-medical prescribing in clinical practice: a mixed-methods systematic review. AB - QUESTION: What are the factors that affect the implementation or utilisation of independent non-medical prescribing (iNMP)? DESIGN: Mixed-methods systematic review. Two reviewers independently completed searches, eligibility and quality assessments. DATA SOURCES: Pre-defined search terms were utilised to search electronic databases. Reference lists, key journals and grey literature were searched alongside consultation with authors/experts. ELIGIBILITY CRITERIA FOR INCLUDED STUDIES: Qualitative and quantitative studies investigating independent prescribing by any non-medical professional group. Study participants included any stakeholders involved in actual or proposed iNMP. Measurements reported on data describing stakeholders' perceptions and experiences of the barriers to/facilitators of iNMP. RESULTS: A total of 43 qualitative and seven quantitative studies from three countries (n=12, 117 participants) were included. Quality scores varied from 9 to 35 (Quality Assessment Tool for Studies with Diverse Designs, 0 to 48). Qualitative data were synthesised into four themes (and subthemes): systems (government and political, organisational, formulary); education and support (non-medical prescribing (NMP) courses/continuous professional development (CPD)); personal and professional (medical profession, NMP professions, service users); and financial factors. Quantitative data corroborated the qualitative themes. Integration of the qualitative themes and quantitative data enabled the development of a NMP implementation framework. CONCLUSION: Barriers to and facilitators of the implementation and utilisation of iNMP are evident, demonstrating multifactorial and context-specific variables within four explicit themes. Professional bodies, politicians, policy and healthcare managers and clinicians could use the resulting NMP implementation framework to ensure the safe and successful implementation and utilisation of NMP. Clinical physiotherapists and other clinicians should consider whether these variables have been adequately addressed prior to adopting NMP into their clinical practice. REGISTRATION: PROSPERO CRD42015017212. [Noblet T, Marriott J, Graham-Clarke E, Rushton A (2017) Barriers to and facilitators of independent non medical prescribing in clinical practice: a mixed-methods systematic review. Journal of Physiotherapy 63: 221-234]. PMID- 28986141 TI - ? PMID- 28986139 TI - Restrictions for reimbursement of interferon-free direct-acting antiviral drugs for HCV infection in Europe. AB - All-oral direct-acting antiviral drugs (DAAs) for hepatitis C virus, which have response rates of 95% or more, represent a major clinical advance. However, the high list price of DAAs has led many governments to restrict their reimbursement. We reviewed the availability of, and national criteria for, interferon-free DAA reimbursement among countries in the European Union and European Economic Area, and Switzerland. Reimbursement documentation was reviewed between Nov 18, 2016, and Aug 1, 2017. Primary outcomes were fibrosis stage, drug or alcohol use, prescriber type, and HIV co-infection restrictions. Among the 35 European countries and jurisdictions included, the most commonly reimbursed DAA was ombitasvir, paritaprevir, and ritonavir, with dasabuvir, and with or without ribavirin (33 [94%] countries and jurisdictions). 16 (46%) countries and jurisdictions required patients to have fibrosis at stage F2 or higher, 29 (83%) had no listed restrictions based on drug or alcohol use, 33 (94%) required a specialist prescriber, and 34 (97%) had no additional restrictions for people co infected with HIV and hepatitis C virus. These findings have implications for meeting WHO targets, with evidence of some countries not following the 2016 hepatitis C virus treatment guidelines by the European Association for the Study of Liver. PMID- 28986142 TI - Limonene protects osteoblasts against methylglyoxal-derived adduct formation by regulating glyoxalase, oxidative stress, and mitochondrial function. AB - Methylglyoxal (MG) is a potent protein glycating agent and an important precursor of advanced glycation end products, which are involved in the pathogenesis of diabetic osteopathy. In this study, we investigated the effects of limonene on MG induced damage in osteoblastic MC3T3-E1 cells. Pretreating cells with limonene prevented MG-induced protein adduct formation, tumor necrosis factor alpha and interleukin-6 release, mitochondrial superoxide production, and cardiolipin peroxidation. In addition, limonene increased glyoxalase I activity, and glutathione and heme oxygenase-1 levels in the presence of MG. Pretreatment with limonene prior to MG exposure reduced MG-induced mitochondrial dysfunction by preventing mitochondrial membrane potential dissipation and adenosine triphosphate loss, and reduced the levels of adenosine monophosphate-activated protein kinase, peroxisome proliferator activated receptor gamma coactivator 1alpha, and nitric oxide. These results demonstrate that limonene may prevent the development of diabetic osteopathy. PMID- 28986143 TI - Validation of calcaneus trabecular microstructure measurements by HR-pQCT. AB - OBJECTIVE: Assessment of calcaneus microstructure using high-resolution peripheral quantitative computed tomography (HR-pQCT) might be used to improve fracture risk predictions or to assess responses to pharmacological and physical interventions. To develop a standard clinical protocol for the calcaneus, we validated calcaneus trabecular microstructure measured by HR-pQCT against 'gold standard' micro-CT measurements. METHODS: Ten human cadaveric feet were scanned in situ using HR-pQCT (isotropic 82MUm voxel size) at 100, 150 and 200ms integration times, and at 100ms integration time following removal of the calcaneus from the foot (ex vivo). Dissected portions of these bones were scanned using micro-computed tomography (micro-CT) at an isotropic 17.4MUm voxel size. HR pQCT images were rigidly registered to those obtained with micro-CT and divided into multiple 5mm sided cubes to evaluate and compare morphometric parameters between the modalities. Standard HR-pQCT measurements (derived bone volume fraction (BV/TVd); trabecular number, Tb.N; derived trabecular thickness, Tb.Thd; derived trabecular spacing, Tb.Spd) and corresponding micro-CT voxel-based measurements (BV/TV, Tb.N, Tb.Th, Tb.Sp) were compared. RESULTS: A total of 108 regions of interest were analysed across the 10 specimens. At all integration times HR-pQCT BV/TVd was strongly correlated with micro-CT BV/TV (r2=0.95-0.98, RMSE=1%), but BV/TVd was systematically lower than that measured by micro-CT (mean bias=5%). In contrast, HR-pQCT systematically overestimated Tb.N at all integration times; of the in situ scans, 200ms yielded the lowest mean bias and the strongest correlation with micro-CT (r2=0.61, RMSE=0.15mm-1). Regional analysis revealed greater accuracy for Tb.N in the superior regions of the calcaneus at all integration times in situ (mean bias=0.44-0.85mm-1; r2=0.70 0.88, p<0.001 versus mean bias=0.63-1.46mm-1; r2<=0.08, p>=0.21 for inferior regions). Tb.Spd was underestimated by HR-pQCT compared to micro-CT, but showed similar trends with integration time and the region evaluated as Tb.N. HR-pQCT Tb.Thd was also underestimated and moderately correlated (r2=0.53-0.59) with micro-CT Tb.Th, independently from the integration time. Stronger correlations, smaller biases and error were found in the scans of the calcaneus ex vivo compared to in situ. CONCLUSION: Calcaneus trabecular BV/TVd and trabecular microstructure, particularly in the superior region of the calcaneus, can be assessed by HR-pQCT. The highest integration time examined, 200ms, compared best with micro-CT. Weaker correlations for microstructure at inferior regions, and also with lower integration times, might limit the use of the proposed protocol, which warrants further investigation in vivo. PMID- 28986145 TI - Peptides for targeting betaB2-crystallin fibrils. AB - Crystallins are a major family of proteins located within the lens of the eye. Cataracts are thought to be due to the formation of insoluble fibrillar aggregates, which are largely composed of proteins from the crystallin family. Today the only cataract treatment that exists is surgery and this can be difficult to access for individuals in the developing world. Development of novel pharmacotherapeutic approaches for the treatment of cataract rests on the specific targeting of these structures. betaB2-crystallin, a member of beta crystallin family, is a large component of the crystallin proteins within the lens, and as such was used to form model fibrils in vitro. Peptides were identified, using phage display techniques, that bound to these fibrils with high affinity. Fibrillation of recombinantly expressed human betaB2-crystallin was performed in 10% (v/v) trifluoroethanol (TFE) solution (pH 2.0) at various temperatures, and its amyloid-like structure was confirmed using Thioflavin-T (ThT) assay, transmission electron microscopy (TEM), and X-ray fiber diffraction (XRFD) analysis. Affinity of identified phage-displayed peptides were analyzed using enzyme-linked immunosorbent assay (ELISA). Specific binding of a cyclic peptide (CKQFKDTTC) showed the highest affinity, which was confirmed using a competitive inhibition assay. PMID- 28986144 TI - Motor axons are guided to exit points in the spinal cord by Slit and Netrin signals. AB - In the spinal cord, motor axons project out the neural tube at specific exit points, then bundle together to project toward target muscles. The molecular signals that guide motor axons to and out of their exit points remain undefined. Since motor axons and their exit points are located near the floor plate, guidance signals produced by the floor plate and adjacent ventral tissues could influence motor axons as they project toward and out of exit points. The secreted Slit proteins are major floor plate repellents, and motor neurons express two Slit receptors, Robo1 and Robo2. Using mutant mouse embryos at early stages of motor axon exit, we found that motor exit points shifted ventrally in Robo1/2 or Slit1/2 double mutants. Along with the ventral shift, mutant axons had abnormal trajectories both within the neural tube toward the exit point, and after exit into the periphery. In contrast, the absence of the major ventral attractant, Netrin-1, or its receptor, DCC caused motor exit points to shift dorsally. Netrin 1 attraction on spinal motor axons was demonstrated by in vitro explant assays, showing that Netrin-1 increased outgrowth and attracted cultured spinal motor axons. The opposing effects of Slit/Robo and Netrin-1/DCC signals were tested genetically by combining Netrin-1 and Robo1/2 mutations. The location of exit points in the combined mutants was significantly recovered to their normal position compared to Netrin-1 or Robo1/2 mutants. Together, these results suggest that the proper position of motor exit points is determined by a "push-pull" mechanism, pulled ventrally by Netrin-1/DCC attraction and pushed dorsally by Slit/Robo repulsion. PMID- 28986146 TI - Age related distribution of 4-hydroxy 2-nonenal immunoreactivity in human retina. AB - The retina is prone to be damaged by oxidative stress (OS), owing to its constant exposure to light, high rate of oxygen consumption and high membrane lipid content. Lipid peroxidation in aging human retina has been shown by biochemical means. However, information on the cellular sites of OS and antioxidant responses in aging human retina remains limited. Here, we show distribution of immunoreactivity (IR) to a marker of lipid peroxidation (4-hydroxy 2-nonenal [HNE] and antioxidant enzymes involved in counteracting lipid peroxidation (glutathione S-transferase-pi1 and glutarexoxin-1) in donor human retinas at different ages (35-91 years; N = 24). Initially, HNE-IR was present in few macular cone outer segments (COS, sixth decade). With aging, IR appeared in many COS and peaked at ninth decade (14 vs 62 per 3850 MUm2 area between 6 and 9 decade; p < 0.001) in the parafovea then seen elsewhere (perifoveal, mid peripheral and nasal). IR was seen in the parafovea of all retinas, whereas it was present in 8/24 of perifoveal and 6/24 of mid-peripheral retinas, indicating that the parafovea is susceptible to undergo lipid peroxidation. Foveolar COS were immunonegative until 81 years, which developed IR later (>83 years). IR to glutathione S-transferase-pi1 was moderate until eight decade and then showed a decrease in photoreceptor cells between ninth and tenth decade, while glutaredoxin-1 maintained a steady expression with aging. Damaged COS were present in aged retinas, and inner segments and photoreceptor nuclei also showed some degree of alterations. Although there was increased lipid peroxidation with aging, cone death was minimal in those retinas. The two antioxidant enzymes studied here, may play a role in protecting photoreceptors against OS with advanced aging. PMID- 28986147 TI - Fractional flow reserve derived from coronary computed tomography angiography reclassification rate using value distal to lesion compared to lowest value. AB - INTRODUCTION: A standardised approach to the interpretation of FFRCT data is currently lacking. We evaluated the rate of reclassification of FFRCT positivity using the FFRCT value distal to an anatomical stenoses compared to the lowest FFRCT value. METHOD: Patients who underwent coronary CTA and FFRCT analysis were eligible. FFRCT value of <= 0.80 was considered positive. Positive FFRCT distal to stenosis was defined as those with a stenoses of >= 25% with an associated FFRCT value of <= 0.80 within 2cm distal to the lesion. Outcome data on subsequent invasive coronary angiography (ICA) and coronary revascularisation were collected with a minimum follow-up of 60 days to account for delay between referral for invasive testing and/or revascularisation and receiving the procedure. RESULT: 192 patients (mean age 60.7 +/- 10.6 years, 67.5% men) were included. FFRCT was positive for lowest FFRCT value in 55.7% of patients. Positive FFRCT value distal to stenosis was found in 31.3%. The overall reclassification rate of those positive for lowest FFRCT value to negative for FFRCT value distal to stenosis was 43.9% (p < 0.01). The reclassification rates were most pronounced for those with intermediate stenoses - 67% for those with < 50% stenoses, p < 0.01; 49% for 50-69% stenoses, p < 0.01. Amongst those who underwent ICA, the rate of revascularization was significant higher for those with positive FFRCT distal to stenosis compared to those positive for lowest FFRCT value (revascularization/ICA = 0.53 vs 0.44, p < 0.01). CONCLUSION: Using FFRCT values distal to a anatomical stenoses, 44% of patients positive for lowest FFRCT value were reclassified as negative for FFRCT value distal to stenosis. Those who underwent ICA, the rate of revascularisation was higher amongst those with positive FFRCT distal to stenosis compared to those positive for lowest FFRCT value. PMID- 28986149 TI - Factors associated with early dramatic recovery following successful recanalization of occluded artery by endovascular treatment in anterior circulation stroke. AB - Endovascular treatment (EVT) significantly increases the recanalization rate and improves functional outcomes in acute ischemic stroke. However, despite successful recanalization by EVT, some stroke patients demonstrate no early dramatic recovery (EDR). We assessed factors associated with EDR following recanalization by EVT. We included subjects with anterior circulation stroke treated with EVT who met the following criteria: Thrombolysis in Cerebral Ischemia scores (TICI) 2b-3 after EVT, lesion volume <70mL as seen on the pre treatment diffusion-weighted imaging (DWI) scan and a baseline NIHSS score >=6. EDR was defined as a >=8-point reduction in the NIHSS score, or NIHSS score of 0 or 1 measured 24h following treatment. Multivariate regression analyses were performed to identify the predictors associated with EDR. Of the 102 patients (mean age, 64.3years; median National Institutes of Health Stroke Scale score, 14), EDR was achieved in 39 patients (38.2%). The median DWI lesion volume was 12mL (interquartile range, 5-25mL). Median onset-to-recanalization time in these patients was 320min (interquartile range, 270-415min). Logistic regression analysis identified a higher initial NIHSS score (OR 1.17, 95% CI 1.03-1.33, P=0.016) and shorter time from onset to recanalization (OR 0.99, 95% CI 0.986 0.997, P=0.003), to be independently associated with EDR. In the setting of pretreatment DWI lesion volume <70mL, a higher initial NIHSS score and faster time from onset to recanalization may be important predictors of EDR following successful EVT. PMID- 28986148 TI - Brain Activity Unique to Orgasm in Women: An fMRI Analysis. AB - BACKGROUND: Although the literature on imaging of regional brain activity during sexual arousal in women and men is extensive and largely consistent, that on orgasm is relatively limited and variable, owing in part to the methodologic challenges posed by variability in latency to orgasm in participants and head movement. AIM: To compare brain activity at orgasm (self- and partner-induced) with that at the onset of genital stimulation, immediately before the onset of orgasm, and immediately after the cessation of orgasm and to upgrade the methodology for obtaining and analyzing functional magnetic resonance imaging (fMRI) findings. METHODS: Using fMRI, we sampled equivalent time points across female participants' variable durations of stimulation and orgasm in response to self- and partner-induced clitoral stimulation. The first 20-second epoch of orgasm was contrasted with the 20-second epochs at the beginning of stimulation and immediately before and after orgasm. Separate analyses were conducted for whole-brain and brainstem regions of interest. For a finer-grained analysis of the peri-orgasm phase, we conducted a time-course analysis on regions of interest. Head movement was minimized to a mean less than 1.3 mm using a custom fitted thermoplastic whole-head and neck brace stabilizer. OUTCOMES: Ten women experienced orgasm elicited by self- and partner-induced genital stimulation in a Siemens 3-T Trio fMRI scanner. RESULTS: Brain activity gradually increased leading up to orgasm, peaked at orgasm, and then decreased. We found no evidence of deactivation of brain regions leading up to or during orgasm. The activated brain regions included sensory, motor, reward, frontal cortical, and brainstem regions (eg, nucleus accumbens, insula, anterior cingulate cortex, orbitofrontal cortex, operculum, right angular gyrus, paracentral lobule, cerebellum, hippocampus, amygdala, hypothalamus, ventral tegmental area, and dorsal raphe). CLINICAL TRANSLATION: Insight gained from the present findings could provide guidance toward a rational basis for treatment of orgasmic disorders, including anorgasmia. STRENGTHS AND LIMITATIONS: This is evidently the first fMRI study of orgasm elicited by self- and partner-induced genital stimulation in women. Methodologic solutions to the technical issues posed by excessive head movement and variable latencies to orgasm were successfully applied in the present study, enabling identification of brain regions involved in orgasm. Limitations include the small sample (N = 10), which combined self- and partner-induced stimulation datasets for analysis and which qualify the generalization of our conclusions. CONCLUSION: Extensive cortical, subcortical, and brainstem regions reach peak levels of activity at orgasm. Wise NJ, Frangos E, Komisaruk BR. Brain Activity Unique to Orgasm in Women: An fMRI Analysis. J Sex Med 2017;14:1380-1391. PMID- 28986150 TI - Microsurgical treatment and outcomes of spinal arteriovenous lesions: Learned from consecutive series of 105 lesions. AB - Spinal arteriovenous lesions (SAVLs), arteriovenous fistulas (AVFs) and arteriovenous malformations (AVMs), are rare and can devastatingly impair spinal cord function. This study aimed to evaluate clinical outcomes after microsurgical treatment with the aid of intraoperative indocyanine green video-angiography (ICG VA) in a large series of patients with SAVLs. We retrospectively reviewed the cases of 95 consecutive patients with 105 SAVLs (77 spinal AVFs, 28 spinal AVMs) who had been treated surgically during 2010-2016 in two hospitals by the same experienced surgeon. All patients had undergone magnetic resonance imaging and digital subtraction angiography preoperatively and were assessed using the modified Aminoff and Logue Scale (mALS). All lesions were resected or occluded using ICG-VA. No ICG-VA-related complications occurred. Compared with AVF, patients with AVM tended to be younger (p<0.001) and were at higher risk of an associated aneurysm (p=0.021), hemorrhage (p<0.001), pain (p<0.001) and abrupt onset (p<0.001). SAVLs were most common in the lower thoracic region (45.71%), and their most common clinical presentation was paresthesia (89.52%). At a mean follow-up of 33.3months, mALS indicated significant improvement in patients with spinal AVFs (p<0.001) and AVMs (p=0.002) compared with their status preoperatively. An improved, stable clinical status was noted at the last follow up in 93.51% of those with AVFs and 89.28% of those with AVMs. Thus, microsurgical treatment of SAVLs produced a lasting positive clinical outcome in a large cohort of consecutive patients. ICG-VA proved to be an efficient intraoperative tool during resection of these lesions, especially in patients with an AVF. PMID- 28986151 TI - BRAF V600E mutation is a significant prognosticator of the tumour regrowth rate in brainstem gangliogliomas. AB - BRAF V600E mutations are progression factors in paediatric low-grade gliomas. Furthermore, a high percentage of paediatric brainstem gangliogliomas have BRAF V600E mutations. However, their clinical significance, including possible connections between the biomarkers and ganglioglioma's clinical features, especially a brainstem counterpart, is unclear. To identify potential molecular features predictive of brainstem ganglioglioma's clinical outcomes, a retrospective cohort of 28 World Health Organization (WHO) grade I brainstem gangliogliomas was analysed for BRAF V600E, IDH1 R132H, and IDH2 R172K mutations, TERT C228T/C250T promoter mutation, H3F3A K27M mutation and MGMT methylation. The volume of tumours was calculated accurately by using 3D Slicer software. The clinical data of these patients were retrospectively analysed. In tumours with BRAF V600E mutations, the tumour regrowth rate was significantly faster than that of the wild type group (p=0.001). Moreover, the BRAF V600E mutant group had shorter progression-free survival (PFS) compared with wild type (p=0.012). On multivariate analysis, no factor was found to be an independent prognostic factor; however, tumours with faster regrowth rates had a strong trend towards an increased risk for shorter PFS (HR=1.027, p=0.056). No statistical analysis could be performed to evaluate factors affecting overall survival (OS). These data suggest that BRAF V600E can predict the regrowth rate of brainstem gangliogliomas after microsurgery, and a BRAF V600E-targeted therapeutic may be a promising early intervention measure for patients who harbour BRAF V600E mutation after microsurgery. PMID- 28986152 TI - Vocal Evaluation of Children with Congenital Hypothyroidism. AB - OBJECTIVE: To evaluate the vocal characteristics of a group of children with congenital hypothyroidism (CH) and the association of these characteristics with the children's clinical, laboratory, and therapeutic profiles. MATHERIAL AND METHODS: Observational, analytical, cross-sectional study including 200 prepubertal children, of whom 100 had CH (study group [SG]) and 100 had no CH (control group [CG]). The following parameters were evaluated: 1) history (identification, complaints, and interfering variables), 2) auditory-perceptual and acoustic evaluation (samples analyzed by a group of specialists, and objectively by a computer program), 3) self-assessment scores in the Pediatric Voice-Related Quality-of-Life (PVRQoL) survey, 4) laryngological evaluation (presence or absence of laryngeal lesions and data regarding glottal closure), and 5) medical records (CH etiology, age at treatment initiation, disease severity at diagnosis, treatment quality, and thyroid function tests on the day of the examination). RESULTS: In the perceptual assessment, 62.6% of the SG children passed, whereas 37.4% failed in the voice screening, but these results were comparable with those in the CG (P = 0.45). Both groups had mean/median acoustic measurements within the normal limits. The mean PVRQoL in the SG (99.3 +/- 2.4) and CG (99.5 +/- 1.7) were comparable (P = 1.00). Both SG (16.7%) and CG (15%) presented vocal cord lesions (P = 1.00). There was no association between voice/larynx characteristics and endocrinological data. CONCLUSION: Prepubescent children diagnosed with CH during neonatal screening and who have a lifelong history of adequate treatment of CH showed similar vocal and laryngeal characteristics compared with children without CH. PMID- 28986153 TI - Contemporary Commercial Music Singing Students-Voice Quality and Vocal Function at the Beginning of Singing Training. AB - OBJECTIVE: The purpose of this study was to assess the voice quality and the vocal tract function in popular singing students at the beginning of their singing training at the High School of Music. DESIGN: This is a retrospective cross-sectional study. METHODS: The study consisted of 45 popular singing students (35 females and 10 males, mean age: 19.9 +/- 2.8 years). They were assessed in the first 2 months of their 4-year singing training at the High School of Music, between 2013 and 2016. Voice quality and vocal tract function were evaluated using videolaryngostroboscopy, palpation of the vocal tract structures, the perceptual speaking and singing voice assessment, acoustic analysis, maximal phonation time, the Voice Handicap Index, and the Singing Voice Handicap Index (SVHI). RESULTS: Twenty-two percent of Contemporary Commercial Music singing students began their education in the High School, with vocal nodules. Palpation of the vocal tract structure showed in 50% correct motions and tension in speaking and in 39.3% in singing. Perceptual voice assessment showed in 80% proper speaking voice quality and in 82.4% proper singing voice quality. The mean vocal fundamental frequency while speaking in females was 214 Hz and in males was 116 Hz. Dysphonia Severity Index was at the level of 2, and maximum phonation time was 17.7 seconds. The Voice Handicap Index and the SVHI remained within the normal range: 7.5 and 19, respectively. Perceptual singing voice assessment correlated with the SVHI (P = 0.006). CONCLUSIONS: Twenty-two percent of the Contemporary Commercial Music singing students began their education in the High School, with organic vocal fold lesions. PMID- 28986154 TI - Ultrasound in acute internal medicine; time to set a European standard. AB - Nowadays point-of-care ultrasound (POCUS) is considered indispensable for critical care and emergency physicians. POCUS is a noninvasive tool, can be done at the bedside, leads to instant diagnostic information and is safe in terms of radiation. POCUS could also be very suitable for internists in the field of acute internal medicine. There are differences between European internists in the use of POCUS from no use at all to more outlined educational programs. In literature there are examples of comprehensive POCUS guidelines which could serve as an example for the European Federation of Internal Medicine (EFIM). In this review some aspects of POCUS are highlighted and the authors encourage EFIM to set European standards for this important development. PMID- 28986155 TI - Using scores to identify patients at risk of short term mortality at arrival to the acute medical unit: A validation study of six existing scores. AB - INTRODUCTION: "Early warning scores" (EWS) have been developed to quantify levels of vital sign abnormality. However, many scores have not been validated. The aim of this study was to validate six scores that all rely on vital signs: Rapid Acute Physiology Score (RAPS), Rapid Emergency Medicine Score (REMS) and the National Early Warning Score (NEWS) and the Goodacre, Groarke and Worthing physiological scores. METHODS: A posthoc single-center observational cohort study of prospectively collected vital signs on acutely admitted medical patients to a Danish hospital. All adult patients arriving at an acute medical unit at a 450 bed regional teaching hospital were included. Upon arrival, we registered initial vital signs and only the first presentation in the study period was included. Patients were included from 1 June to 31 October 2012. All-cause 24-h mortality and overall in-hospital mortality were used as endpoints. A discriminatory power above 0.8 was considered acceptable. RESULTS: 5784 patients were included with a median age of 67 (49-78) years, 32 (0.6%) died within 24h and 161 (2.8%) while admitted. Discriminatory power for 24h mortality was above 0.8 for all scores (except the Groarke score (0.587)) and highest for the Worthing score (0.847). The discriminatory power for predicting overall in-hospital mortality was highest for the Goodacre and Worthing scores (0.810 and 0.800 respectively) but below 0.8 for the remaining scores. CONCLUSION: The Goodacre score and the Worthing physiological score have good discriminatory power at identifying patients at increased risk of 24-h and in-hospital mortality in our setting. PMID- 28986156 TI - Technological aided assessment of the acutely ill patient - The case of postoperative complications. AB - Surgical interventions come with complications and highly reported mortality after major surgery. The mortality may be a result of delayed detection of severe complications due to lower monitoring frequency in the general wards. Several studies have shown that continuous monitoring is superior to the manually intermittent recorded monitoring in terms of detecting abnormal physiological signs. Hopefully improved observations may result in earlier detection and clinical intervention. This narrative review will describe current monitoring possibilities for postoperative patients and how it may prevent complications. Several wireless systems are being developed for monitoring vital parameters, but many of these are not yet validated for critically ill patients. The ultimate goal with patient monitoring and detect of events is to prevent postoperative complications, death and costs in the health care system. A few studies indicate that monitoring systems detect deteriorating patients earlier than the nurses, and this was associated with less clinical instability. An important caveat of future devices is to assess their effect in relevant patient populations and not only in healthy test-subjects. Implementation of novel technologies is expensive although expected to be cost-effective if just few adverse events can be prevented. The future is here with promising devices and the possibility to give an unprecedented precise risk estimation of adverse post-surgical events. Next step is to integrate existing evidence based treatment algorithms to demonstrate the clinical efficacy of implementing the new technology. PMID- 28986158 TI - Pioneers in pulmonary medicine. PMID- 28986157 TI - Quality of medication related information in discharge letters: A prospective cohort study. PMID- 28986159 TI - Age-specific and year of birth changes in hospital admissions during a period of unexplained higher deaths in England. AB - BACKGROUND: Policy makers have assumed that increase in medical demands and costs are attributable to the increasing age of the population and the inability of health and social care to limit demand. METHODS: Analysis of data obtained from NHS and Office of National Statistics. RESULTS: Population-adjusted age-specific patterns in medical admissions and deaths have increased over the period 2012/13 to 2015/16 in the NHS in England. The growth is both age and year of birth specific, and the youngest appear to be worst affected. Overall there has been a growth of 30,870 admissions (15% increase) in 25-29year olds compared to 119,280 extra admissions (7% increase) for 70-74year olds. Admissions of younger medical patients have also increased more so than for pneumonia, and the increase in all cause mortality appears to be influenced by the patients' year of birth. CONCLUSION: In England, medical admissions and deaths (all-cause mortality) have recently displayed very high unexplained growth. The fact that these are associated with patient year of birth suggests that the cause(s) may be related to infectious or other environmental factors encountered earlier in life. PMID- 28986160 TI - Superior safety of dual therapy with dabigatran and clopidogrel vs. triple therapy with warfarin, aspirin and clopidogrel in the RE-DUAL PCI trial: What is key, the strategy or the drug? PMID- 28986161 TI - Screening of the frail patient in the emergency department: A systematic review. AB - BACKGROUND: Several frailty rating scales have been developed to detect and screen for the level of frailty. It is uncertain what diagnostic value screening of frailty level have in the emergency department. AIM: To assess the accuracy of the screening tools used in the emergency department to detect frailty in patients>=65years by their ability to identify the risk of adverse outcomes. METHODS: An extensive medical literature search of Embase and PubMed was conducted, to identify studies using frailty screening scales in the emergency department. Data was subsequently extracted and evaluated from the results of the included studies. RESULTS: Four studies met the exact inclusion criteria. Four different frailty screening scales: Clinical Frailty Scale, Deficit Accumulation Index, Identification of Seniors At Risk and The Study of Osteoporotic Fracture frailty index used in the emergency department were described and compared. Predictive values for various outcomes are represented and discussed. CONCLUSIONS: The results suggest that frailty successfully predicts increased risk of hospitalization, nursing home admission, mortality and prolonged length of stay after an initial emergency department visit. Frailty does however not predict increased risk of 30day emergency department revisit. Further research highlighting the value of screening for frailty level in elderly emergency department patients is needed. LEARNING POINTS: Although frail elders in need of further geriatric assessment should be identified as soon as possible, this systematic review only identified four cohort studies of frailty assessment in emergency departments. Although frailty screening appeared to predict the risk of mortality and of admission to hospital/nursing home, these four studies did not show that it could predict return visits to emergency departments within 30days. Randomized clinical trials of frailty screening tools compared to usual care or other methods of assessment are clearly needed. PMID- 28986162 TI - Development and preliminary validation of the Salzburg Stress Eating Scale. AB - Stress-related eating has long been a focus of study in several disciplines. Currently available psychometric scales conflate stress-related eating with emotional eating despite that not all stress states can be subsumed under some form of specific emotion. Moreover, existing measures primarily assess increased food intake in response to emotions and stress, thus ignoring evidence of decreased food intake in response to stress. Therefore, we drew from established stress concepts to develop the first genuine stress-related eating scale (Salzburg Stress Eating Scale [SSES]) in both German and English versions. In the SSES higher scores indicate eating more when stressed and lower scores indicate eating less when stressed. In study 1 (n = 340), the German SSES was found to have a one-factor structure (alpha = 0.89). SSES scores were weakly or moderately correlated with other eating-related constructs (e.g., emotional eating, body mass index [BMI]), and weakly correlated or uncorrelated with non-eating-related constructs (e.g., impulsivity, perceived stress); in addition, women had higher scores than men. Perceived stress moderated the association between stress eating and BMI, such that higher SSES scores were significantly related to higher BMI in individuals with high perceived stress, but not in individuals with low perceived stress. In studies 2 (n = 790) and 3 (n = 331), factor structure, internal consistency, and associations with sex and BMI were replicated for both German and English versions of the SSES. Hence, the SSES represents a psychometrically sound tool for the measurement of stress-related eating. PMID- 28986163 TI - The reception of Darwin in late nineteenth-century German paleontology as a case of pyrrhic victory. AB - This paper investigates German-speaking paleontologists' reception of Darwin's thought and the ways in which they negotiated their space of knowledge production accordingly. In German-speaking regions, the majority of paleontologists welcomed Darwin's magnum opus, since it granted paleontology an independent voice within biology, and thus a new institutional setting. However, in the process of negotiating the features of paleontology within the Darwinian framework, German paleontologists constrained their practices too narrowly, for fear of leaving open possible results at odds with the burgeoning Darwinian biological community. In doing so, they also limited the further development of German paleontology. In other words, paleontologists Karl Alfred von Zittel (1839-1904) and Melchior Neumayr (1845-1890) advocated for a handmaid's role for paleontology, which increased biologists' dependence on paleontologists for empirical evidence, but which limited paleontologists' theoretical autonomy. By analyzing both the institutional strategies and the methodology of German-speaking paleontology at the end of the nineteenth century, this paper shows the importance of scientists' ability to enter into and negotiate their place within the broader biological community. PMID- 28986164 TI - Circulating ApoJ is closely associated with insulin resistance in human subjects. AB - OBJECTIVE: Insulin resistance is a major risk factor for type 2 diabetes. ApolipoproteinJ (ApoJ) has been implicated in altered pathophysiologic states including cardiovascular and Alzheimer's disease. However, the function of ApoJ in regulation of glucose homeostasis remains unclear. This study sought to determine whether serum ApoJ levels are associated with insulin resistance in human subjects and if they change after interventions that improve insulin sensitivity. METHODS: Serum ApoJ levels and insulin resistance status were assessed in nondiabetic (ND) and type 2 diabetic (T2D) subjects. The impacts of rosiglitazone or metformin therapy on serum ApoJ levels and glucose disposal rate (GDR) during a hyperinsulinemic/euglycemic clamp were evaluated in a separate cohort of T2D subjects. Total ApoJ protein or that associated with the HDL and LDL fractions was measured by immunoblotting or ELISA. RESULTS: Fasting serum ApoJ levels were greatly elevated in T2D subjects (ND vs T2D; 100+/-8.3 vs. 150.6+/-8.5AU, P<0.0001). Circulating ApoJ levels strongly correlated with fasting glucose, fasting insulin, HOMA-IR, and BMI. ApoJ levels were significantly and independently associated with HOMA-IR, even after adjustment for age, sex, and BMI. Rosiglitazone treatment in T2D subjects resulted in a reduction in serum ApoJ levels (before vs. after treatment; 100+/-13.9 vs. 77+/ 15.2AU, P=0.015), whereas metformin had no effect on ApoJ levels. The change in ApoJ levels during treatment was inversely associated with the change in GDR. Interestingly, ApoJ content in the LDL fraction was inversely associated with HOMA-IR. CONCLUSION: Serum ApoJ levels are closely correlated with the magnitude of insulin resistance regardless of obesity, and decrease along with improvement of insulin resistance in response only to rosiglitazone in type 2 diabetes. PMID- 28986165 TI - Metabolic phenotyping using kinetic measurements in young and older healthy adults. AB - BACKGROUND: The aging process is often associated with the presence of sarcopenia. Although changes in the plasma concentration of several amino acids have been observed in older adults, it remains unclear whether these changes are related to disturbances in whole body production and/or interconversions. METHODS: We studied 10 healthy young (~22.7y) and 17 older adults (~64.8y) by administering a mixture of stable amino acid tracers in a pulse and in a primed constant infusion. We calculated whole body production (WBP) and metabolite to metabolite interconversions. In addition, we measured body composition, muscle function, and provided questionnaires to assess daily dietary intake, physical activity, mood (anxiety, depression) and markers of cognitive function. Plasma enrichments and metabolite concentrations were measured by GC- and LC-MS/MS and statistics were performed by student t-test. RESULTS: Older adults had a 11% higher body mass index (p=0.04) and 27% reduced peak leg extension force (p=0.02) than the younger group, but comparable values for muscle mass, mood and cognitive function. Although small differences in several plasma amino acid concentrations were observed, we found older adults had about 40% higher values of WBP for glutamine (221+/-27 vs. 305+/-21MUmol/kgffm/h, p=0.03) and tau-methylhistidine (0.15+/-0.01 vs. 0.21+/-0.02MUmol/kgffm/h, p=0.04), 26% lower WBP value for arginine (59+/-4 vs. 44+/-4MUmol/kgffm/h, p=0.02) and a reduction in WBP (50%; 1.23+/-0.15 vs. 0.69+/-0.06MUmol/kgffm/h, p=0.001) and concentration (25%; 3.5+/ 0.3MUmol/l vs. 2.6+/-0.2MUmol/l, p=0.01) for beta-Hydroxy beta-Methylbutyrate. No differences were observed in protein catabolism. Clearance of arginine was decreased (27%, p=0.03) and clearance of glutamine (58%, p=0.01), leucine (67%, p=0.001) and KIC (76%, p=0.004) were increased in older adults. CONCLUSIONS: Specific differences exist between young and older adults in amino acid metabolism. PMID- 28986167 TI - Nonlocal grazing in patterned ecosystems. AB - Many ecosystems exhibit gapped, labyrinthine, striped or spotted patterns. Important examples are vegetation patterns in drylands: these patterns are viewed as precursors of a catastrophic transition to a degraded state. A possible source of degradation is overgrazing, but many current spatially extended models include grazing in a local linear way. In this article nonlocal grazing responses are derived, taking into account (1) how many consumers there are (demographic response) (2) where they are (aggregative response) and (3) how much they forage (functional response). Different assumptions lead to different grazing responses, the type of grazing has a large influence on how ecosystems adapt to changing environmental conditions. In dryland simulations the different types of grazing are shown to alter the desertification process driven by decreasing rainfall. A sufficiently strong aggregative response leads to the suppression of vegetation patterns, nuancing their role as generic early warning signals. PMID- 28986166 TI - Sildenafil induces browning of subcutaneous white adipose tissue in overweight adults. AB - OBJECTIVE: To investigate that short-term treatment of sildenafil can induce browning of subcutaneous white adipose tissue (sWAT) in human adults. DESIGN: A randomized, double-blinded, placebo-controlled, parallel group trial. METHODS: Sixteen eligibility overweight male subjects were recruited, comparing 100mg/day sildenafil versus an identical placebo therapy for 7days. sWAT samples were collected from subjects before and after 7-day sildenafil or placebo interventions. RESULTS: The results showed that multilocular UCP1-positive adipocytes existed in sWAT samples from subjects after sildenafil treatment. Compared to before treatment in both group as well as after treatment in placebo, sildenafil significantly decreased adipocyte size, increased the expressions of UCP1 protein and mRNA, mitochondrial density, and leak respiratory capacity in sWAT (p<0.05). Sildenafil also increased plasma cyclic guanosine-3',5' monophosphate (cGMP) and catecholamine concentrations (p<0.05), and consequently activated the expressions of vasodilator-stimulated phosphoprotein (VASP) and p70 ribosomal S6 kinase 1 (S6K1) (p<0.05). Sildenafil did not activate typical brown fat. CONCLUSIONS: The current findings demonstrate that sildenafil can induce browning of sWAT in human, and this action may be through cGMP-dependent protein kinase I and mechanistic/mammalian target of rapamycin (mTOR) signaling pathways. Sldenafil may be a promising treatment for metabolic disease. PMID- 28986168 TI - Highly specific delivery of siRNA to hepatocytes circumvents endothelial cell mediated lipid nanoparticle-associated toxicity leading to the safe and efficacious decrease in the hepatitis B virus. AB - Lipid nanoparticles (LNPs) are the leading technology for delivering short interfering RNA (siRNA) in vivo. While numerous attempts to improve the efficiency of siRNA delivery have been reported, only a few studies of the mechanism of LNP-mediated toxicity and attempts to develop safe LNPs in vivo have been reported, in spite of the significance of such systems, in the light of treatment and clinical applications. We herein report on the elucidation of the mechanism of hepatotoxicity following the intravenous injection of a high dose of hepatotropic LNPs. The LNPs accumulated in liver sinusoidal endothelial cells (LSECs), resulting in their activation and the induction of several cytokines related to neutrophils, followed by neutrophilic inflammation. To circumvent this toxic cascade, the LNPs were modified with a hepatocyte-specific ligand, N-acetyl d-galactosamine (GalNAc), which resulted in a substantial improvement of hepatocyte-specificity and in a dramatic reduction in toxicity. Moreover, modification of the GalNAc-LNPs with polyethyleneglycol abrogated the LNP associated toxicity without any detectable loss of gene silencing activity in hepatocytes. Finally, we observed that a single injection of the LNPs resulted in a significant reduction of hepatitis B virus (HBV) genomic DNA and their antigens without any sign of toxicity in chimeric mice with humanized livers that had been persistently infected with HBV. These lines of the fact suggest that the newly designed siRNA-loaded LNPs promise to be a useful technology for the treatment of liver diseases. PMID- 28986169 TI - RIFM fragrance ingredient safety assessment, 3,7-dimethyl-2,6-nonadienenitrile, CAS Registry Number 61792-11-8. PMID- 28986170 TI - RIFM fragrance ingredient safety assessment, Methylcyclooctyl carbonate, CAS Registry Number 61699-38-5. PMID- 28986171 TI - Early indications of ANIT-induced cholestatic liver injury: Alteration of hepatocyte polarization and bile acid homeostasis. AB - Hepatocyte polarization is essential for biliary secretion, and loss of polarity causes bile secretory failure and hepatotoxicity. Here, we showed that alpha naphthyl isothiocyanate (ANIT)-induced liver injury was accompanied by the dynamic interruption of bile acid homeostasis in rat plasma, liver and bile, which was characterized by the redistribution of bile acids in plasma and bile and a small range of fluctuations in the liver. Molecular mechanism studies indicated that these factors are dynamically mediated by the disruption of bile acid transporters and hepatic tight junctions. Dynamic changes in tight junction (TJ) permeability were observed by hepatobiliary barrier function assessment. Hepatocyte polarization was disrupted by ANIT before the development of cholestatic hepatotoxicity and alteration of bile acid metabolic profiles, which were assayed by high-performance liquid chromatography-tandem mass spectrometry, further verifying TJ deficiency. S1PR1 activation with SEW2871 reduced ANIT induced liver injury by reducing the total serum bile acid concentration, liver functional enzyme activity and inflammation. Our data suggest that hepatocyte polarization plays an important role in maintaining bile acid homeostasis before the development of cholestatic hepatotoxicity and that TJs were more prominent in the early stage of cholestasis. S1PR1 may be a potential target for the prevention of drug-induced cholestatic liver injury. PMID- 28986172 TI - Nicotine affects rat Leydig cell function in vivo and vitro via down-regulating some key steroidogenic enzyme expressions. AB - Nicotine is consumed largely as a component of cigarettes and has a potential effect on pubertal development of Leydig cells in males. To investigate its effects, 49-day-old male Sprague Dawley rats received intraperitoneal injections of nicotine (0.5 or 1 mg/kg/day) for 2 weeks and immature Leydig cells were isolated from the testes of 35-day-old rats and treated with nicotine (0.05-50 MUM). Serum hormones, Leydig cell number and related gene expression levels after in vivo treatment were determined and medium androgen levels were measured and cell cycle, apoptosis, mitochondrial membrane potential (?Psim), and reactive oxygen species (ROS) of Leydig cells after in vitro treatment were measured. In vivo exposure to nicotine lowered serum luteinizing hormone, follicle stimulating hormone, and testosterone levels and reduced Leydig cell number and gene expression levels. Nicotine in vitro inhibited androgen production in Leydig cells by downregulating the expression levels of P450 cholesterol side cleavage enzyme, 3beta-hydroxysteroid dehydrogenase 1, and steroidogenic factor 1 at different concentration ranges. In conclusion, nicotine disrupts Leydig cell steroidogenesis during puberty possibly via down-regulating some key steroidogenic enzyme expressions. PMID- 28986173 TI - Early passage autologous mesenchymal stromal cells accelerate diabetic wound re epithelialization: A clinical case study. PMID- 28986175 TI - Clinical Case Discussion: Primary Treatment for Prostate Cancer in an Elderly Man Treatment of the Primary Tumor is Necessary. AB - The decision-making process for treatment of prostate cancer should not be based on a single parameter such as patient age but should account for cancer characteristics, life expectancy, comorbidities, and patient expectation. Local treatment might be beneficial in selected elderly men with aggressive disease and a long life expectancy. PMID- 28986174 TI - Cell density, dimethylsulfoxide concentration and needle gauge affect hydrogel induced bone marrow mesenchymal stromal cell viability. AB - Mesenchymal stromal cells (MSCs) have shown potential therapeutic benefits for a range of medical disorders and continue to be a focus of intense scientific investigation. Transplantation of MSCs into injured tissue can improve wound healing, tissue regeneration and functional recovery. However, implanted cells rapidly lose their viability or fail to integrate into host tissue. Hydrogel seeded bone marrow (BM)-MSCs offer improved viability in response to mechanical forces caused by syringe needles, cell density and dimethylsulfoxide (DMSO) concentration, which in turn, will help to clarify which factors are important for enhancing biomaterial-induced cell transplantation efficiency and provide much needed guidance for clinical trials. In this study, under the control of cell density (<2 * 107 cells/mL) and final DMSO concentration (<0.5%), hydrogel induced BM-MSC viability remained >82% following syringe needle passage by 25- or 27-gauge needles, providing improved cell therapeutic approaches for regenerative medicine. PMID- 28986176 TI - Diffuse gliomas exhibit whole brain impaired cerebrovascular reactivity. AB - PURPOSE: Cerebral diffuse gliomas exhibit perilesional impaired cerebrovascular reactivity (CVR), yet the degree of impairment as well as its full spatial extent in the brain remains unknown. With quantitative fMRI, we studied twelve subjects with untreated brain diffuse glioma and twelve healthy controls to assess CVR impairment and determine its distribution throughout the brain. METHODS: In a prospective case-control study, quantitative CVR measurements were derived from BOLD fMRI volumes during standardized iso-oxic changes in carbon dioxide. Whole brain CVR was assessed with additional detailed analyses using specific tumor and tissue masks and compared to datasets of healthy controls. RESULTS: Whole brain CVR was significantly impaired compared to healthy controls (0.11+/-0.10 versus 0.28+/-0.8, p<0.01). All diffuse glioma patients exhibited even more severely impaired intralesional CVR (mean 0.01+/-0.06). Increasing tumor volume significantly correlated with severity of intralesional CVR impairment (p<0.05, R2=0.38), and whole brain CVR impairment (p<0.05, R2=0.55). CONCLUSION: Patients with brain diffuse glioma exhibit intralesional and whole brain impaired CVR with severity correlating to tumor volume. Quantitative fMRI may be entertained to study antitumor therapy efficacy by tracking CVR changes and may have a complementary role to better interpret BOLD associated neurovascular uncoupling. PMID- 28986177 TI - Weight of evidence approaches for the identification of endocrine disrupting properties of chemicals: Review and recommendations for EU regulatory application. AB - A Weight-of-evidence (WoE) evaluation should be applied in assessing all the available data for the identification of endocrine disrupting (ED) properties of chemicals. The European Commission draft acts specifying criteria under the biocidal products and plant protection products regulations require that WoE is implemented for the assessment of such products. However, only some general considerations and principles of how a WoE should be conducted are provided. This paper reviews WoE approaches to distil key recommendations specifically for the evaluation of potential ED properties of chemicals. In a manner, which is consistent with existing, published WoE frameworks, the WoE evaluation of ED properties can be divided into four phases: 1) Definition of causal questions and data gathering and selection, 2) Review of individual studies, 3) Data integration and evaluation, and 4) Drawing conclusions based on inferences. Recommendations are made on how to conduct each phase robustly and transparently to help guide the WoE evaluation of potential endocrine disrupting properties of chemicals within a European regulatory context. PMID- 28986178 TI - Neuropharmacological and acute toxicological evaluation of ethanolic extract of Allamanda cathartica L. flowers and plumieride. AB - Psychiatric diseases affect more than 350 million people all over the world, and medicinal plants have been considered the basis for pharmacological research. The study investigates the anticonvulsant and antidepressant-like activities and acute toxicological effects of ethanolic extract of Allamanda cathartica flowers, and plumieride. The extract was analyzed by HPLC and plumieride was isolated. Toxicity studies were carried out on females Wistar rats (2000 mg/kg). Toxicity was evaluated by measuring biochemical parameters and conducting histopathological analysis. For pharmacological evaluation different doses of the extract (100, 150 and 300 mg/kg, p.o.) and plumieride (0.5, 1 and 2 MUg/kg, i.p.) were administered before the Forced-Swimming Test (FST), pentylenetetrazole seizure test (PTZT) or Tail-Suspension Test (TST) in mice. Furthermore, hemolytic activity, cytotoxicity and micronucleus test were performed. In addition, mutagenicity and reproductive/developmental toxicity were estimated by TEST software analysis. Data show that both treatments induce significant antidepressive-like effect in FST and TST, but not anticonvulsant effect. The effect of plumieride last up to 4 h after treatment. No signs of toxicity, mutagenicity, cytotoxicity or hemolytic activity were observed. The TEST-software demonstrated that plumieride present reproductive/developmental toxicity. Together, the data obtained show that the flowers extract and plumieride present antidepressant-like effect and did not present signals of acute toxicity. PMID- 28986179 TI - Acute and subchronic toxicity studies of seabuckthorn (Hippophae rhamnoides L.) oil in rodents. AB - Seabuckthorn (Hippophae rhamnoides L.) has been traditionally used as medicine and nutritional supplement for a long period of time. However, information on the systemic toxicity and safety evaluation of seabuckthorn and its extracts is still scarce. The purpose of this study was to evaluate the potential toxicity of seabuckthorn oil by an acute oral toxicity study in mice and a 90-day repeated oral toxicity study in rats. No mortality or signs of toxicity was observed in mice treated with 20 mL/kg body weight seabuckthorn oil in the acute toxicity study. In the subchronic toxicity study, 80 Sprague-Dawley rats (10 animals per sex per treatment group) were administrated with 10, 5, 2.5 and 0 (control) mL/kg body weight of seabuckthorn oil daily for 90 days by gavage. There were no signs of toxicity and treatment-related changes in rats treated with seabuckthorn oil on mortality, body and organ weights, food consumption, blood biochemistry and hematology, gross necropsy and histopathological examinations. Based on the finding of this study, the maximum tolerated dose of seabuckthorn oil was >20 mL/kg for mice for acute toxicity study, and the no-observed-adverse-effect level was 10 mL/kg body weight for both male and female rats for 90-day toxicity study. PMID- 28986180 TI - Reply to: Don't kill passive oxygenation with continuous oxygen insufflation too fast in cardiac arrest ventilation. PMID- 28986181 TI - "Early detection of brain death using the Bispectral Index (BIS) in patients treated by extracorporeal cardiopulmonary resuscitation (E-CPR) for refractory cardiac arrest". PMID- 28986182 TI - On the transdiagnostic nature of peripheral biomarkers in major psychiatric disorders: A systematic review. AB - The search for biomarkers has been a leading endeavor in biological psychiatry. To analyze its evolution over the years, we performed a systematic review to evaluate (a) the most studied peripheral molecular markers in major psychiatric disorders, (b) the main features of studies proposing them as biomarkers and (c) whether their patterns of variation are similar across disorders. Of the six molecules most commonly studied as plasmatic markers of schizophrenia, major depressive disorder or bipolar disorder, five (BDNF, TNF-alpha, IL-6, C-reactive protein and cortisol) were the same across diagnoses. An analysis of this literature showed that, while 66% of studies compared patients and controls, only 34% were longitudinal, and only 10% presented a measure of diagnostic or prognostic efficacy. Meta-analyses showed variation in the levels of these molecules to be robust across studies, but similar among disorders, suggesting them to reflect transdiagnostic systemic consequences of psychiatric illness. Based on this, we discuss how current publication practices have led to research fragmentation across diagnoses, and suggest approaches to face this issue. PMID- 28986183 TI - No 353 - Traitements visant la vessie hyperactive : Accent sur la pharmacotherapie - Addenda. PMID- 28986184 TI - No. 353-Treatments for Overactive Bladder: Focus on Pharmacotherapy - An Addendum. AB - OBJECTIVE: This technical update addendum reviews success rates and comparative evidence of the anticholinergic fesoterodine, as well as mechanism of action, safety profile, success rates, and comparative evidence of the beta3 agonist mirabegron in the treatment of non-neurogenic overactive bladder syndrome (OAB). This adds to OAB pharmacotherapy recommendations initially published in 2012. INTENDED USERS: Residents and other trainees, primary care practitioners, gynaecologists, urologists, urogynaecologists, and other health care providers who assess, counsel, and treat women with OAB. TARGET POPULATION: Adult women with symptomatic OAB. OPTIONS: This addition relates to fesoterodine, mirabegron, and anticholinergic-beta3 agonist combination pharmacotherapy. OUTCOMES: The outcomes of interest are clinical efficacy of fesoterodine compared with no treatment or other OAB therapies; mechanism of action and safety profile of mirabegron, clinical efficacy of mirabegron compared to no treatment or other OAB therapies; clinical efficacy of anticholinergic-beta3 agonist combination pharmacotherapy for OAB. EVIDENCE: PubMed, Medline, and the Cochrane Database were searched using the key words "fesoterodine" and "mirabegron." Results were restricted to English or French and human clinical and pharmacological research. Animal research and clinical studies including only male participants were excluded. Articles were included until the end of December 2016. Grey literature was not searched. Clinical practice guidelines, guidelines of specialty societies, and systematic reviews were included. RCTs and observational studies were included when evidence for the outcome of interest or in the target population was not available from systematic reviews. New studies not yet included in systematic reviews were also included. References of included articles were also searched to ensure comprehensive inclusion of relevant literature. VALUES: The content and recommendations were drafted and agreed upon by the principal author, as well as members of the Urogynaecology Committee. The Board of the SOGC approved the final draft for publication. The quality of evidence was rated using the criteria described in the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology framework. The Summary of Findings is available upon request. BENEFITS, HARMS, AND/OR COSTS: It is expected that this technical update will benefit patients with OAB by providing physicians and other interested health care providers with additional options for and knowledge of safe and effective OAB pharmacotherapy. The benefits clearly outweigh the potential harms or costs of implementation of this technical update, although there are no direct harms or costs identified. UPDATES: "Evidence will be reviewed 5 years after publication to decide whether all or part of the document should be updated. However, if important new evidence is published prior to the 5-year cycle, the review process may be accelerated for a more rapid update of some recommendations." SPONSORS: Not applicable. RECOMMENDATIONS: PMID- 28986185 TI - Fertility-Sparing Management Using Progestin for Young Women with Endometrial Cancer From a Population-Based Study. AB - OBJECTIVE: For young women with complex atypical endometrial hyperplasia (CAH) and endometrial cancer (EC) who choose to preserve fertility, progestin therapy is the mainstay of treatment. The objective of this study was to evaluate oncologic and reproductive outcomes associated with progestin therapy among these women from a population-based cancer registry. METHODS: This was a retrospective population-based cohort study of women under age 45 in British Columbia from 2003 to 2015 with CAH or grade I endometrioid EC who used progestins as initial management. Demographics, treatment type, response to treatment, determinants of definitive surgery (hysterectomy), pathologic findings, and obstetrical outcomes were reviewed. RESULTS: There were 50 women under age 45 with CAH (n = 29) and EC (n = 21). Median age at diagnosis was 36 years (range 25-41), and most were nulliparous (88%) with a median BMI of 32.9 (range 21-70). After 6 months of therapy, 58% of women had persistent disease, and only 35% had full resolution at last follow-up (median 23 months). There were 32 women who had a hysterectomy, including 27 because of persistent/recurrent disease, and 5 who chose surgery despite complete response to progestins. The majority of hysterectomy specimens (85%) had minimal or no residual pathology, even among those with disease on preoperative biopsy. Only 10% of women had successful pregnancies. CONCLUSION: There is a moderate to high risk of persistence of CAH or EC on progestin therapy. However, for those undergoing hysterectomy, the vast majority has low risk disease confined to the endometrium, implying the possibility of further conservative management of persistent disease. PMID- 28986186 TI - Fatal Abdominal Compartment Syndrome Due to Severe Triglyceride-Induced Pancreatitis in Early Pregnancy. AB - Serum levels of maternal lipids rise physiologically in normal pregnancy, and women with underlying hypertriglyceridemia may experience dramatic elevations which place them at risk for pancreatitis. We describe the case of a woman with severe familial hypertriglyceridemia and prior pancreatitis who discontinued her lipid-lowering therapy early in pregnancy. She promptly developed severe abdominal pain and was hospitalized with acute pancreatitis during the late first trimester. Despite aggressive medical treatment and critical care monitoring, she developed abdominal compartment syndrome (ACS) with associated acute renal failure, which progressed to cardiorespiratory failure and was ultimately fatal. ACS is an alarming complication of acute pancreatitis that has been poorly studied in pregnancy. PMID- 28986188 TI - Factors that support change in the delivery of midwifery led care in hospital settings. A review of current literature. AB - PROBLEM: In hospital units, the network of interdependent relationships between midwives and doctors has positioned midwives within hierarchical relationships of power. Others argue that the physical layout of hospital wards created by biomedicine makes it difficult for midwives to provide midwifery led care. The aim of this review is to identify factors that support change in the delivery of the midwifery led care in hospital settings. METHODS: A narrative review was chosen as this method allows for greater flexibility in the selection of studies and can lead to the inclusion of a wider range of literature. RESULTS: Eight high quality papers from the UK, Sweden, Canada and Australia were selected for review. Papers focused on improving the delivery of midwife led care in hospital midwifery units, labour and postnatal wards. Key themes were identified as supporting change in the delivery of midwifery led care were ownership of change, capability to change and transformational leadership. CONCLUSION: The findings demonstrate the importance of social support and clinical leadership in bringing about subtle changes in hospital based midwifery led care. Ultimately improved understanding of the factors that support the delivery of the midwifery led care in hospital settings may improve women's choice and highlight the role of the midwife as the practitioner of normal childbirth. PMID- 28986189 TI - Prevention of Cytomegalovirus Reactivation in Haploidentical Stem Cell Transplantation. AB - Cytomegalovirus (CMV) infection can increase the morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Because of a higher degree of immunosuppression, haploidentical transplant recipients may be at an increased risk of viral infections, particularly CMV. We retrospectively analyzed 86 haploidentical HCT recipients at our institution to determine whether a more intensified antiviral strategy would reduce the incidence of CMV reactivation compared with a traditional antiviral prophylaxis regimen. According to practice changes over time in antiviral prophylaxis at our institution, patients were divided into the following 3 groups: hybrid (n = 15), traditional (n = 26), and intermediate dose (n = 45). The hybrid group received valganciclovir from admission to day -2 followed by standard-dose valacyclovir. The traditional group received standard-dose valacyclovir starting on day -1. The intermediate-dose group received ganciclovir from admission through day -2, followed by intermediate-dose valacyclovir. The hybrid and intermediate-dose groups were combined into an intensified group for further analysis. We found the cumulative incidence (CI) of CMV reactivation within 100 days post-HCT was higher for patients receiving the traditional strategy compared with the hybrid and intermediate-dose strategy groups (81% versus 53% versus 71%, respectively; P = .08) and was significantly higher when the traditional group was compared against the intensified group (81% versus 67%, respectively; P = .032). Median time to CMV reactivation was also shorter in the traditional group versus the intensified group (31 versus 41 days, respectively). Moreover, the CI of CMV disease by day 100 was significantly worse for patients receiving the traditional prophylaxis strategy among the 3 groups (8% traditional versus 0% hybrid versus 0% intermediate dose; P = .032). Renal toxicity did not differ between the traditional and intensified group. In conclusion, an intensified approach to prevention of CMV reactivation was associated with lower incidence of CMV reactivation and less CMV disease without increased toxicity. Because the most benefit was observed in the intensified group, further studies are needed to assess which antiviral intervention is the most beneficial on lowering the rates of CMV viremia and disease. PMID- 28986187 TI - Aldose reductase inhibitor, fidarestat regulates mitochondrial biogenesis via Nrf2/HO-1/AMPK pathway in colon cancer cells. AB - Although we have shown earlier that aldose reductase (AR) inhibitors prevent colorectal cancer cell (CRC) growth in culture as well as in nude mice xenografts, the mechanism(s) is not well understood. In this study, we have investigated how AR inhibition prevents CRC growth by regulating the mitochondrial biogenesis via Nrf2/HO-1 pathway. Incubation of CRC cells such as SW-480, HT29, and HCT116 with AR inhibitor, fidarestat that non-covalently binds to the enzyme, increases the expression of Nrf2. Further, fidarestat augmented the EGF-induced expression of Nrf2 in CRC cells. Fidarestat also increased the Nrf2 -DNA binding activity as well as expression of HO-1 and NQO1 and activation of SOD and catalase in SW480 cells. Similarly, in nude mice xenograft tumor tissues, Nrf2 and HO-1 levels were significantly higher in fidarestat-treated mice compared to controls. Further, stimulation of CRC cells with EGF in the presence of fidarestat increased the mRNA levels of PGC-1alpha, Nrf1 and TFAM and protein levels of PGC-1alpha, TFAM and COX-IV and decreased the mitochondrial DNA damage as measured by 8-hydroxy-2'-deoxyguanosine levels. AR inhibitor also modulated the phosphorylations of AMPK and mTOR and expression of p53 in EGF treated cells. Collectively, our results indicate that AR inhibitor prevents CRC growth by increasing mitochondrial biogenesis via increasing the expression of Nrf2/HO-1/AMPK/p53 and decreasing the mitochondrial DNA damage. PMID- 28986190 TI - Incidence and Risk Factors for Nontuberculous Mycobacterial Infection after Allogeneic Hematopoietic Cell Transplantation. AB - Allogenic hematopoietic stem cell transplant (HCT) recipients are at risk of many infections. Nontuberculous mycobacteria (NTM) are increasingly recognized as clinically significant pathogens in this population. We investigated the incidence and risk factors for NTM infection after allogeneic HCT. This retrospective cohort study included all patients with allogeneic HCT at our institution during 2001 to 2013. Patients who developed significant NTM infection (NTM disease) were identified. Multivariable modeling was used to identify risk factors for NTM disease, and a risk score model was constructed to identify high risk patients. Of 1097 allogeneic HCT patients, 45 (4.1%) had NTM isolated and 30 (2.7%) had NTM disease (28 [93.3%] exclusively pulmonary, 2 [6.7%] pulmonary plus another site). Incidence of NTM infection by competing risk analysis was 2.8% at 5 years (95% CI, 1.9% to 4.0%). The median time to diagnosis was 343 days (range, 19 to 1967). In Fine-Gray proportional hazards modeling, only global severity of chronic graft-versus-host disease (cGVHD) (HR, 1.99; 95% CI, 1.12 to 3.53; P = .019,) and cytomegalovirus (CMV) viremia (HR, 5.77; 95% CI, 1.71 to 19.45; P = .004) were significantly associated with NTM disease. Using these variables a risk score was calculated: 1 point for CMV viremia or moderate cGVHD and 2 points for severe cGVHD. The score divided patients into low risk (0 to 1 points, n = 820 [77.3%], 3-year NTM risk 1.2%), intermediate risk (2 points, n = 161 [15.4%], 3-year NTM risk 7.1%), and high risk (3 points, n = 56 [5.4%], 3-year NTM risk 14.3%). NTM disease after allogeneic HCT is common. Severe cGVHD and CMV viremia are associated with increased risk, permitting risk stratification. PMID- 28986191 TI - JAID/JSC Guidelines for Infection Treatment 2015-Intestinal infections. PMID- 28986192 TI - Effect of antibiotics for infectious diarrhea on the duration of hospitalization: A retrospective cohort study at a single center in Japan from 2012 to 2015. AB - OBJECTIVE: Routine empirical antimicrobial therapy for patients with infectious diarrhea is not recommended in general practice. Conversely, prescription of empirical antibiotics for hospitalized patients remains controversial due to a lack of studies providing evidence for its benefits. Thus, this study aimed to examine whether empirical antimicrobial therapy would shorten the hospitalization duration for infectious diarrhea patients. METHODS: This single-center, retrospective cohort study was performed at the Department of General Medicine and Emergency Care, Toho University Medical Center Omori Hospital, using medical records. Adult patients (aged >=16 years) hospitalized for infectious diarrhea from 2012 to 2015 were enrolled. The primary outcome was the duration of hospitalization. Risk factors examined in parallel to antibiotic therapy included age, sex, relevant medical history, probiotics use, vital signs, leukocyte count, liver and renal functions, and microbiological data. RESULTS: We enrolled 138 and 50 patients treated with and without antimicrobial therapy, respectively. The median hospitalization periods were 6.0 days (interquartile range, 4.0-7.0 days) and 5.0 days (interquartile range, 3.25-6.0 days) for patients treated with and without antibiotics, respectively (p = 0.007). Multiple regression showed that empiric antimicrobial therapy (p = 0.017), advanced age (p = 0.003), hematochezia (p = 0.008), elevated serum creatinine (p < 0.001), and elevated serum C-reactive protein (p = 0.002) were significant risk factors of longer hospitalization duration. CONCLUSION: Empirical antimicrobial therapy was found to relate to a longer hospitalization duration for infectious diarrhea patients. Although its effects on the patients' symptoms were not evaluated, our results suggest that empirical antimicrobial therapy should be administered cautiously to not only outpatients, but also hospitalized patients. PMID- 28986193 TI - Insight into lipophilicity of deoxyribonucleoside-boron cluster conjugates. AB - Lipophilicity was investigated for 20 2'-deoxyribonucleoside derivatives modified with electron-neutral 1,2-dicarba-closo-dodecaborane, 1,12-dicarba-closo dodecaborane, 7,8-dicarba-nido-undecaborate anion, and metallacarborane containing Co, Fe, or Cr. The partition coefficient (P) for neutral conjugates and the distribution coefficient (D7.4) for ionic compounds were determined as a lipophilicity descriptor using a shake-flask method. All modified nucleosides had P/D7.4 values higher than those of an appropriate unmodified 2'-closo dodecaborane and metallacarborane was found to be three orders of magnitude higher than that of its unmodified counterpart. The lowest impact on the P/D7.4 values of the conjugates was observed for the 7,8-dicarba-nido-undecaborate anion. A preliminary molecular modeling study of a thymidine-carborane conjugate with beta-cyclodextrin confirmed the ability of the components to form an inclusion complex. PMID- 28986194 TI - Dry powder coated osmotic drug delivery system. AB - Dry powder coated osmotic drug delivery system (ODDS) were prepared and characterized using an innovative powder coating technology. Coating powder adhesion to the surface of the ODDS core was firstly performed through an electrostatic spray gun, followed by a curing step to allow those electrically deposited particles coalesce and form a continuous, uniform and strong coating film, which is the semipermeable membrane of the ODDS. Triethyl citrate (TEC) was found to be a better liquid plasticizer than PEG 400 both in reducing the glass transition temperature of the coating polymer (cellulose acetate) and in increasing the electrical conductivity of the ODDS cores, both of which led to an enhanced coating powder adhesion and film formation. Results of SEM indicated that the uniformity of the coating film varied significantly with the difference of curing time and temperature. Salbutamol sulfate and ibuprofen were used as the model drugs. Release profiles of both showed that zero-order drug release kinetics was achieved. Release rate of both drugs from powder coated ODDS could be adjusted by changing the coating level but was independent of the agitation speed and of the pH of the release media. PMID- 28986195 TI - Surface-modified mucoadhesive microgels as a controlled release system for miconazole nitrate to improve localized treatment of vulvovaginal candidiasis. AB - The use of conventional vaginal formulations of miconazole nitrate (MN) in the treatment of deep-seated VVC (vulvovaginal candidiasis) is limited by poor penetration capacity and low solubility of MN, short residence time and irritation at the application site. Surface-modified mucoadhesive microgels were developed to minimize local irritation, enhance penetration capacity and solubility and prolong localized vaginal delivery of MN for effective treatment of deep-seated VVC. Solid lipid microparticles (SLMs) were prepared from matrices consisting of hydrogenated palm oil (Softisan(r) 154, SF) and super-refined sunseed oil (SO) with or without polyethylene glycol (PEG)-4000, characterized for physicochemical performance and used to prepare mucoadhesive microgels (MMs) encapsulating MN, employing Polycarbophil as bioadhesive polymer. The MMs were evaluated for physicochemical performance and in vitro drug release in simulated vaginal fluid (pH=4.2), whereas mucoadhesive, rheological and stability tests, anticandidal efficacy in immunosuppressed estrogen-dependent female rats and vaginal tolerance test in rabbits were performed with optimized formulation. The amorphicity of 1:9 phytolipid blend (SO:SF) was increased in the presence of PEG 4000. The physicochemical properties of the SLMs and MMs indicated their suitability for vaginal drug delivery. Overall, MN-loaded PEGylated MMs exhibited significantly (p<0.05) more prolonged drug release than non-PEGylated MMs. Additionally, optimized PEGylated MMs was stable at 40+/-2 degrees C over a period of 6months, viscoelastic, mucoadhesive, non-sensitizing, histopathologically safe and gave remarkably (p<0.05) higher reduction in Candida albicans load (86.06%) than Daktarin(r) (75.0%) and MN-loaded polymeric-hydrogel (47.74%) in treated rats in 12days. Thus, PEGylated MMs is promising for effective and convenient treatment of VVC. PMID- 28986196 TI - Effect of composition of simulated intestinal media on the solubility of poorly soluble compounds investigated by design of experiments. AB - The composition of the human intestinal fluids varies both intra- and inter individually. This will influence the solubility of orally administered drug compounds, and hence, the absorption and efficacy of compounds displaying solubility limited absorption. The purpose of this study was to assess the influence of simulated intestinal fluid (SIF) composition on the solubility of poorly soluble compounds. Using a Design of Experiments (DoE) approach, a set of 24 SIF was defined within the known compositions of human fasted state intestinal fluid. The SIF were composed of phospholipid, bile salt, and different pH, buffer capacities and osmolarities. On a small scale semi-robotic system, the solubility of 6 compounds (aprepitant, carvedilol, felodipine, fenofibrate, probucol, and zafirlukast) was determined in the 24 SIF. Compound specific models, describing key factors influencing the solubility of each compound, were identified. Although all models were different, the level of phospholipid and bile salt, the pH, and the interactions between these, had the biggest influences on solubility overall. Thus, a reduction of the DoE from five to three factors was possible (11 13 media), making DoE solubility studies feasible compared to single SIF solubility studies. Applying this DoE approach will lead to a better understanding of the impact of intestinal fluid composition on the solubility of a given drug compound. PMID- 28986197 TI - Studying of drug solubility in water and alcohols using drug-ammonium ionic liquid-compounds. AB - Synthesis of three mefenamic acid (MEF) derivatives - ionic liquid compounds composed of MEF in an anionic form and ammonium cation (choline, MEF1), or {di(2 hydroxyethyl)dimethyl ammonium (MEF2)}, or {tri(2-hydroxyethyl)methyl ammonium compound (MEF3)} is presented. The basic thermal properties of pure compounds i.e. fusion temperatures, and the enthalpy of fusion of these compounds have been measured with differential scanning microcalorimetry technique (DSC). Molar volumes have been calculated with the Barton group contribution method. The solubilities of MEF1, MEF2 and MEF3 using the dynamic method were measured at constant pH in a range of temperature from (290 to 370) K in three solvents: water, ethanol and 1-octanol. The experimental solubility data have been correlated by means of three commonly known GE equations: the Wilson, NRTL and UNIQUAC with the assumption that the systems studied here present simple eutectic behaviour. The activity coefficients of pharmaceuticals at saturated solutions in each binary mixture were calculated from the experimental data. The formation of MEF-ionic liquid compounds greatly increases the solubility in water in comparison with pure MEF or complexes with 2-hydroxypropyl-beta-cyclodextrin. The development of these compounds formulations will assist in medication taking into account oral solid or gel medicines. PMID- 28986198 TI - Role of Hyperhomocysteinemia and Hyperuricemia in Pathogenesis of Atherosclerosis. AB - BACKGROUND: The mechanisms of hyperhomocysteinemia (HHcy) and hyperuricemia (HUA) that promote atherosclerosis were seldom explored and always indefinite. Therefore, we will discuss some new reviews about the role of HHcy and HUA in the pathogenesis of atherosclerosis. METHODS: This study was conducted by reading a lot of literature, including basic research and clinical application research. RESULTS: HHcy is known as an independent risk factor for atherosclerosis. Possible mechanisms for the association between homocysteine and atherosclerosis include stimulating smooth muscle cell growth, reducing endothelial cell growth and endothelial cell relaxation, and decreasing synthesis of high-density lipoprotein. HUA causes endothelial dysfunction and thereby increases oxidative stress, inducing vascular smooth muscle cell proliferation and reducing endothelial nitric oxide bioavailability. HUA plays a role in the development and pathogenesis of metabolic syndrome, hypertension, stroke, and atherosclerosis. CONCLUSIONS: Accelerated atherosclerosis may be a consequence of the combined effect of HHcy and HUA. PMID- 28986199 TI - Vascular Parkinsonism in a Tertiary Care Stroke Prevention Clinic and the Development of a New Screening Strategy. AB - OBJECTIVES: To determine the prevalence of vascular parkinsonism (VasP) in a stroke prevention clinic (SPC). BACKGROUND: VasP can be defined by an onset of parkinsonism with prominent gait problems occurring within 1 year of stroke. METHODS: We created a screening strategy based on the Tanner Questionnaire (TQ), a validated scale for parkinsonism, and the creation of a 4-point Five-Minute Assessment Scale (FMAS) operationalizing Zijlmans' criteria for the diagnosis of VasP. Consecutive stroke patients were screened over a 12-month period using the TQ and the FMAS. SAS statistical software was used. RESULTS: Two hundred forty patients (52.5% females) were screened (mean age of 65 years, standard deviation, 14.5). Twenty-five percent of patients had a TQ score >= 4 with a median FMAS of 2. In this group, 32.6% (15/46) were found to have parkinsonism. Seventeen percent (8/46) were diagnosed with VasP having an FMAS of 4. Seventy-five of the participants obtained a TQ <= 3, with a median FMAS of 1. Only 1 patient in this group had parkinsonism (1.9%; 1/194). Using a cutoff of 4 points in the TQ resulted in a sensitivity of 93.8%, a specificity of 86.2% for parkinsonism, and a sensitivity of 100% with a specificity of 83% for VasP. Patients with FMAS = 4 (VasP) attained higher scores in the TQ with a median of 5 (Spearman rank correlation coefficient for the TQ and the FMAS (rs) = .447, P < .0005). CONCLUSIONS: We documented a prevalence of 3% (8/240) for VasP in an SPC. We propose a new, easier, and unified 2-step TQ-FMAS screening strategy for this condition. PMID- 28986200 TI - Serum Alkaline Phosphatase, Phosphate, and In-Hospital Mortality in Acute Ischemic Stroke Patients. AB - BACKGROUND: The clinical impacts of serum alkaline phosphatase (ALP) and phosphate on early death are not fully understood in patients with acute ischemic stroke. We examined the associations between serum ALP, phosphate, and in hospital mortality after ischemic stroke. METHODS: Serum ALP and phosphate were measured in 2944 ischemic stroke patients from 22 hospitals in Suzhou City from December 2013 to May 2014. Cox proportional hazard models and restricted cubic splines were used to estimate the relationships between serum ALP and phosphate (both as categorical and continuous variables) and risk of in-hospital mortality. RESULTS: During hospitalization, 111 patients (3.7%) died from all causes. After multivariable adjustment, the hazard ratio (HR) of the highest quartile compared with the lowest quartile of ALP was 2.19 (95% confidence interval [CI], 1.20 4.00) for early death. Restricted cubic spline analysis indicated a significant linear association between ALP and death (P-linearity = .017). A U-shaped association of phosphate with in-hospital mortality was observed (P-nonlinearity = .011). Compared with the third quartile of phosphate (1.08-1.21 mmol/L), HRs of the lowest and highest quartiles for early death were 2.17 (1.15-4.08) and 1.70 (.88-3.30), respectively. Sensitivity analyses further confirmed our findings. CONCLUSIONS: We observed a graded relationship between serum ALP levels and risk of early death in patients with acute ischemic stroke. There was a U-shaped association between phosphate and all-cause mortality with significantly increased risk among patients with lower phosphate levels. PMID- 28986201 TI - Detection of anti-mitochondrial antibodies by immunoprecipitation in patients with systemic sclerosis. AB - OBJECTIVE: To describe a new immunoprecipitation pattern identified in Italian patients affected by systemic sclerosis (SSc), corresponding to the pyruvate dehydrogenase antigen complex recognized by anti-mitochondrial antibodies (AMA) in primary biliary cholangitis (PBC). METHODS: Autoantibodies in sera from 85 patients with SSc were tested by protein- and RNA-immunoprecipitation. Immunoprecipitation-Western blot was used to determine the identified proteins, and medical records re-evaluated for liver function tests and PBC. RESULTS: In 13/85 (15%) SSc sera, a unique set of 75-50-40-34kD proteins that had not been previously reported, was noted. The four proteins were identified as the proteins X/E3BP, E1alpha, E1beta, and E2/E3 of the pyruvate dehydrogenase antigen complex by immunoprecipitation-Western blot. From clinical record evaluation, 9/13 (69%) SSc patients with this new pattern were positive for AMA by routine indirect immunofluorescence, and 7/13 (54%) had a diagnosis of PBC, while 4/13 (31%) manifested no biochemical signs of cholestasis. Twelve of 13 patients with SSc and AMA by immunoprecipitation have a limited cutaneous form of SSc and anti centromere antibodies. CONCLUSIONS: We describe a pattern of 4 proteins in 15% of SSc patients, identified for the first time by protein-immunoprecipitation. This pattern corresponds to serum AMA against the pyruvate dehydrogenase antigen complex and it must be considered in the interpretation of protein immunoprecipitation results. PMID- 28986202 TI - Multiple enterovirus genotypes circulating in children hospitalized with acute gastroenteritis in Thailand. AB - Enterovirus (EV) infection is widespread and can lead to a broad range of clinical symptoms, from mild to severe forms of disease. EVs are not always classified as pathogen and the epidemiological surveillance of EV infection in acute gastroenteritis cases in Thailand remains unexplored. This study aims to investigate the frequency, seasonality and molecular characteristics of EV circulating in children hospitalized with acute gastroenteritis in Chiang Mai, Thailand from 2010 to 2014. A total of 1266 fecal samples were included in this study. RT-PCR amplification of the 5'UTR was used for EV screening and phylogenetic analysis of the VP1 sequence was performed for EV genotyping. EV was detected in 5.8% of infections (73 out of 1266). Based on VP1 sequence analysis, over half (50.8%) of the identified EV cases were caused by species C, and the next two most frequent were species B and A (35.4% and 13.8%, respectively). This study identified 28 different EV genotypes, EV-C96 and coxsackievirus A24 were the most frequent genotype detected (12.3% each). EV was detected throughout the year with an increase of detection rate in December-January and May-June. In conclusion, this study reported the prevalence of EV infection with a wide variety of EV genotypes in children with acute diarrhea. PMID- 28986203 TI - Inhaled nebulised unfractionated heparin improves lung function in moderate to very severe COPD: A pilot study. AB - BACKGROUND: COPD is an inflammatory airway disease characterised by progressive airflow limitation and air trapping, leading to lung hyperinflation and exercise limitation. Acute worsening of symptoms, including dyspnea, cough and sputum production, occurs during exacerbations which are associated with significantly reduced health related quality of life, and increased morbidity and mortality. Chronic bronchial mucus production and productive cough are risk factors for exacerbations. Medicines targeting bronchoconstriction and airway inflammation are the current mainstays of COPD therapy. However, there is growing concern with an increased risk of pneumonia in patients with COPD receiving regular inhaled corticosteroids and there is therefore a need to find safer alternative treatments. Previous studies have indicated that inhalation of unfractionated heparin (UFH) treats local inflammation, mucus hypersecretion and lung injury, without systemic anticoagulation, and is safe. Therefore, our primary objective was to demonstrate that inhaled UFH significantly improves lung function (FEV1) over 21 days of treatment in patients with COPD receiving pulmonary rehabilitation and that UFH provides a novel, safe and effective way of treating this complex disease. METHODS: Forty patients with moderate to very severe COPD admitted to the IRCCS San Raffaele Pisana Hospital for 21 days pulmonary rehabilitation were randomised to receive nebulised inhaled UFH (75,000 or 150,000 IU BID) or placebo for 21 days. All patients also received nebulised salbutamol (1 mg) and beclomethasone dipropionate (400 MUg) BID over the same period. Lung function was measured at day 0, 7, 14 and 21 of treatment and at a follow-up visit 7 days post-treatment. Exercise capacity (6MWT) and dyspnoea (Borg score) were measured before and after treatment. In pre-clinical studies, the ability of basic proteins found in COPD sputum to neutralise the anticoagulant activity of heparin was determined using the AMAX heparin assay kit. MAIN RESULTS: At both doses, UFH significantly increased FVC following 7 days of treatment and 150,000 IU BID significantly increased FEV1 (+249 +/- 69 ml compared with placebo) at this time, an effect maintained to the 28 day follow up. Clinically significant improvement in exercise capacity and dyspnoea were seen after 21 days of treatment with both doses of UFH. There were no serious adverse events or effects on systemic coagulation. Pre-clinical studies demonstrated that the basic proteins lactoferrin, platelet factor-4 (PF-4), IL-8 and polyarginine, as a model of the eosinophil cationic protein (ECP), found in COPD sputum neutralise the anticoagulant activity of heparin. CONCLUSION: Inhaled nebulised UFH is safe and provides additional clinical benefit for patients with moderate to very severe COPD through effects that are independent of its anticoagulant activity. PMID- 28986204 TI - Cough and severe asthma. PMID- 28986205 TI - [Conception and implementation of a novel E-learning module with EbM learning contents in operative dentistry]. AB - PURPOSE: Computer-assisted learning (CAL) programs are becoming more widely used in medical and dental training. However, the combination of CAL programs and evidence-based education in dentistry has not been described previously. The aim was to determine the acceptance and user-friendliness of a CAL program combined with evidence-based training. METHODS: The didactic concept of the module includes the case-oriented, problem-based embedding of a total of 32 EbM learning assignments, which can be completed interactively and self-determinedly in an interdisciplinary context using focus patients with different diseases. The present study was conducted at the Dental School of the Goethe University in Frankfurt/Main. Data on acceptance and user-friendliness were collected from three consecutive cohorts of 114 dental students attending their first clinical semester. They used the "Toothache Walk-in Clinic: FOCUS" CAL, which can be downloaded via the Internet. The instrument consisted of 64 statements. The first part addressed general information about the user. The second part contained 43 specific statements on the CAL program. These included factors A (handling and technical aspects), B (content and functional range), and C (didactics and suitability for education). Possible responses ranged from 0 to 3 (0 = strongly disagree, 3 = strongly agree). RESULTS: All of the 114 questionnaires distributed were returned (response rate 100%). Most users (90.1%) considered the topics of evidence-based dentistry important for their training. They rated the program by using German school grades, and the overall rating was 2.26 (SD = 0.64). Most students (88.6%) considered the program useful for their clinical training in the treatment of patients. The mean scores for the 43 specific items amounted to 1.90 (factor A, SD = 0.63), 1.55 (factor B, SD = 1.93), and 2.23 (factor C, SD = 0.79). CONCLUSIONS: The CAL program with dental medicine vignettes and learning elements for evidence-based medicine received a primarily positive assessment. Students welcome that EbM contents are offered as part of their dental studies curriculum. PMID- 28986206 TI - Frequency dependent hub role of the dorsal and ventral right anterior insula. AB - The right anterior insula (rAI) plays a crucial role in generating adaptive behavior by orchestrating multiple brain networks. Based on functional separation findings of the insula and spectral fingerprints theory of cognitive functions, we hypothesize that the hub role of the rAI is region and frequency dependent. Using the Human Connectome Project dataset and backtracking approach, we segregate the rAI into dorsal and ventral parts at frequency bands from slow 6 to slow 3, indicating the frequency dependent functional separation of the rAI. Functional connectivity analysis shows that, within lower than 0.198 Hz frequency range, the dorsal and ventral parts of rAI form a complementary system to synchronize with externally and internally-oriented networks. Moreover, the relationship between the dorsal and ventral rAIs predicts the relationship between anti-correlated networks associated with the dorsal rAI at slow 6 and slow 5, suggesting a frequency dependent regulation of the rAI to brain networks. These findings could improve our understanding of the rAI by supporting the region and frequency dependent function of rAI and its essential role in coordinating brain systems relevant to internal and external environments. PMID- 28986207 TI - The role of the temporoparietal junction (TPJ) in action observation: Agent detection rather than visuospatial transformation. AB - Recognizing and understanding the actions of others is usually coupled with perceiving someone else's body movements from a third person perspective (3pp) whereas we perceive our own actions from a first person perspective (1pp). From a neural viewpoint, a recent finding is that perceiving actions from a 3pp as compared to a 1pp activates the temporoparietal junction, a brain region associated with visuospatial transformation and perspective taking but also with mental state inference and Theory of Mind (ToM). The present fMRI study characterizes the response profile of TPJ to elucidate its role in action observation. Participants observed naturalistic and pixelized object-directed actions from a 3pp and 1pp. Critically, in the pixelized condition the action goal could only be inferred from the movement kinematics. Both left and right TPJ revealed an interaction: Neural activity in TPJ was enhanced for 3pp vs. 1pp actions in the naturalistic but not pixelized condition. This finding contradicts theories proposing that TPJ is generally involved in transforming the action into the observer's perspective to match perceived body movements with visuomotor representations in the observer's motor system, which would be particularly required when actions can only be inferred from movement kinematics. Instead, our results support the theory that perceptual 3pp-selective cues trigger ToM-related processes such as detection of other agents and reasoning about an action's underlying mental states. PMID- 28986208 TI - Dynamic functional connectivity and brain metastability during altered states of consciousness. AB - The scientific study of human consciousness has greatly benefited from the development of non-invasive brain imaging methods. The quest to identify the neural correlates of consciousness combined psychophysical experimentation with neuroimaging tools such as functional magnetic resonance imaging (fMRI) to map the changes in neural activity associated with conscious vs. unconscious percepts. Different neuroimaging methods have also been applied to characterize spontaneous brain activity fluctuations during altered states of consciousness, and to develop quantitative metrics for the level of consciousness. Most of these studies, however, have not explored the dynamic nature of the whole-brain imaging data provided by fMRI. A series of empirical and computational studies strongly suggests that the temporal fluctuations observed in this data present a non trivial structure, and that this structure is compatible with the exploration of a discrete repertoire of states. In this review we focus on how dynamic neuroimaging can be used to address theoretical accounts of consciousness based on the hypothesis of a dynamic core, i.e. a constantly evolving and transiently stable set of coordinated neurons that constitute an integrated and differentiated physical substrate for each conscious experience. We review work exploring the possibility that metastability in brain dynamics leads to a repertoire of dynamic core states, and discuss how it might be modified during altered states of consciousness. This discussion prompts us to review neuroimaging studies aimed to map the dynamic exploration of the repertoire of states as a function of consciousness. Complementary studies of the dynamic core hypothesis using perturbative methods are also discussed. Finally, we propose that a link between metastability in brain dynamics and the level of consciousness could pave the way towards a mechanistic understanding of altered states of consciousness using tools from dynamical systems theory and statistical physics. PMID- 28986210 TI - Spinal fracture in diffuse idiopathic skeletal hyperostosis. PMID- 28986209 TI - Effects of prenatal alcohol exposure in a prospective sample of young adults: Mental health, substance use, and difficulties with the legal system. AB - INTRODUCTION: Few studies have focused on the transition to adulthood in adults with prenatal alcohol exposure (PAE). In this study, we examine the occurrence of problem behavior at this transition, including mental health problems, substance use, and difficulties with the legal system. The sample is prospective and provides an opportunity to examine effects of a wide range of prenatal exposure. Adults with PAE were expected to show more problem behavior; the impact of level of exposure was examined as well. METHOD: The sample was drawn from a predominantly low-income, African-American population. Mothers of the alcohol exposed participants (n=123) and those in the non-exposed SES-Control group (CONT) (n=59) were recruited at a prenatal visit when information on alcohol and drug use during pregnancy was collected. A disability contrast group (n=54) was recruited at adolescence. The adults with PAE were assigned to three groups varying in physical and cognitive effects of exposure. This report is based on the adults' responses to interviews or questionnaires on problem behavior and laboratory tests related to substance use. RESULTS: Adults with PAE showed more problem behavior in all three areas than adults from the CONT group. For mental health problems, the exposed group showing cognitive, but not physical effects, had the highest scores; their scores were similar, however, to those of the disability contrast group on several scales. Results for outcomes on substance use and legal difficulties were less consistent, but, when significant effects occurred, the group that was exposed, but neither physically nor cognitively affected, was more likely to show negative outcomes. Males in this group were most involved in these behaviors. CONCLUSION: Effects of PAE continue into early adulthood and affect mental health problems, substance use, and interactions with the legal system. Adults who are exposed, but less physically affected, seem to be the most involved in problem behavior. More research is necessary to examine environmental effects in conjunction with PAE on these outcomes and to provide a basis for developing potential interventions. PMID- 28986211 TI - In vivo evaluation of hemerythrin-based oxygen carriers: Similarities with hemoglobin-based counterparts. AB - We have previously proposed the annelid-derived protein, hemerythrin, as a viable replacement for hemoglobin in the synthesis of semi-synthetic oxygen carriers ("blood substitutes"). Here, we report the first in vivo tests for potential hemerythrin-based oxygen carriers (HrBOC), using a battery of experiments involving Wistar rats and previously tested on a series of hemoglobin-based oxygen carrier candidates (HBOC). At the concentrations tested, hemerythrin appears to behave similarly to hemoglobin - including, importantly, immunological effects. The antioxidant strategies based on albumin as well as based on rubrerythrin appear to offer observable physiological advantages. PMID- 28986212 TI - Synthesis and characterization of modified chitosan via microwave route for novel antibacterial application. AB - Herein we report the synthesis of novel antibacterial graft [Chit-g-Poly (AA-co An)] and crosslink [Chit-cl-Poly (AA-co-An)] copolymer, consisting of acrylic acid (AA), acrylonitrile (An) and chitosan by using the microwave route, and it has been observed that grafting and crosslinking copolymers possess excellent antimicrobial properties. Studies of antibacterial activities of graft and crosslink samples were carried out against gram positive [Staphylococcus aureus (S. aureus)], gram negative [Escherichia coli (E. coli) and Pseudomonas aeroginosa (P. aeroginosa)] bacteria. The graft [Chit-g-Poly (AA-co-An)] and crosslink [Chit-cl-Poly (AA-co-An)] copolymers were characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), thermogravimetric analysis (TGA), X-ray diffraction (XRD) techniques etc to study structural characteristics of synthesised chitosan derivatives. The graft [Chit-g Poly (AA-co-A)] copolymer showed excellent antibacterial activities against E. coli, P. aeroginosa and S. euros 30, 31 and 26mm zone inhibition, respectively, while [Chit-cl-Poly (AA-co-A)] showed antibacterial activities against E. coli, P. aeroginosa and S. euros 26, 36 and 21mm zone inhibition respectively. PMID- 28986213 TI - Characterization of nuclear factor of activated T-cells-c3 (NFATc3) and gene expression of upstream-downstream signaling molecules in response to immunostimulants in Pacific red snapper cells. AB - The nuclear factor of activated T cells (NFAT) proteins have crucial roles in the development and function of the immune system since they not only regulate activation of T cells but are also involved in the control of thymocyte development and T-cell differentiation. In this study, NFATc3 was characterized from the Pacific red snapper, Lutjanus peru. LpNFAtc3, which contains an open reading of 3300 bp frame coding for a protein of 1100 aa with a predicted molecular weight of 118.52 kDa. The predicted protein showed a conserved NFAT family structure with signature motifs and domains, sharing high identity (up to 76%) compared to other fish sequences. NFATc3 gene expression was analyzed by real time-PCR in head-kidney cells (leukocytes and lymphocytes) following yeast, zymosan and Vibrio parahaemolyticus stimulation along with the expression of upstream (ILF2, ILF3 and CaN) and downstream (CD3, TCRbeta, IL-6 and IL-12) molecules. This study revealed a broad expression of NFATc3 with a relative strong expression in intestine and lymphocytes. The expression of NFATc3 was differentially up-regulated after stimulation with yeast in head-kidney leukocytes and after bacterial infection in lymphocytes at 24 h. Interestingly, the yeast and zymosan were able to activate ILF2, ILF3 and CaN mRNA gene expression in both kinds of cells. On the other hand, NFAT downstream genes such as CD3, TCRbeta, IL-6 and IL-12 were significantly up-regulated in leukocytes stimulated with yeast or zymosan at 12 h; however in lymphocytes, this up regulation was detected when cells reacted to V. parahaemolyticus stimuli at 24 h. Stimulating Pacific red snapper leukocytes with immunostimulants as yeast significantly up-regulated the expression of NFATc3, and up- and down-stream molecular genes and NFATc3 lymphocytes expression were potentially involved in responses to invasion of bacterial pathogens in an early immune response. PMID- 28986214 TI - Different roles of a novel shrimp microRNA in white spot syndrome virus (WSSV) and Vibrio alginolyticus infection. AB - In this study, Marsupeneaus japonicus microRNA-S5 (miR-S5) was found to be up regulated 24 h post white spot syndrome virus (WSSV) or V. alginolyticus infection. The loss of function using an anti-microRNA oligonucleotide (AMO-miR S5) showed that expression levels of multiple innate immune-related genes were affected. The expression of p53 and tumor necrosis factor-alpha (TNF-alpha) were significantly down-regulated, expression of myosin was significantly up regulated. The miR-S5 knockdown delayed WSSV-induced death for 48 h, but the final mortality was not affected, while V. alginolyticus-induced mortality was increased by 30%. The effect of miR-S5 knockdown on phagocytosis and apoptosis rates showed that miR-S5 knock down significantly decreased phagocytosis rate of WSSV from 27.8% to 7.0%, and phagocytosis rate of V. alginolyticus from 27.2% to 21.4%, separately. WSSV-induced apoptosis decreased from 60.83% to 51.25%, but no effect on V. alginolyticus-induced apoptosis (43.72%-45.04%). We concluded that miR-S5 could be used by WSSV via regulating hemocyte phagocytosis and apoptosis processes, but helps to defend against bacterial infection by regulating the proPO system, superoxide dismutase activity and phagocytosis. PMID- 28986215 TI - The ethics of maternal-fetal surgery. AB - Maternal-fetal surgery is performed on two patients, the pregnant patient and the fetal patient. Ethics is therefore an essential dimension of maternal-fetal surgery. From its beginnings in only a few centers, various procedures have become available in highly specialized centers in developed countries. Innovation and research have played an indispensable role in the development of maternal fetal surgery and will continue to do so. In this article we present ethically justified criteria, based on the ethical concept of the fetus as a patient, for clinical innovation and research of maternal-fetal surgery and for the professionally responsible transition from innovation and research into clinical practice. These criteria are designed to be used by clinical innovators, clinical investigators, and by oversight committees. PMID- 28986216 TI - Innate immune responses against rock bream iridovirus (RBIV) infection in rock bream (Oplegnathus fasciatus) following poly (I:C) administration. AB - Poly (I:C) showed promise as an immunoprotective agents in rock bream against rock bream iridovirus (RBIV) infection. In this study, we evaluated the time dependent virus replication pattern and antiviral immune responses in RBIV infected rock bream with and without poly (I:C) administration. In the poly (I:C)+virus-injected group, virus copy numbers were more than 18.9-, 24.0- and 479.2-fold lower than in the virus only injected group at 4 (4.73 * 104 and 8.95 * 105/MUl, respectively), 7 (3.67 * 105 and 8.81 * 106/MUl, respectively) and 10 days post infection (dpi) (1.26 * 105 and 6.02 * 107/MUl, respectively). Moreover, significantly high expression levels of TLR3 (8.6- and 7.7-fold, at 4 and 7 dpi, respectively) and IL1beta (3.6-fold at 2 dpi) were observed in the poly (I:C)+virus-injected group, but the expression levels were not significantly in the virus-injected group. However, IL8 and TNFalpha expression levels showed no statistical significance in both groups. Mx, ISG15 and PKR were significantly highly expressed from 4 to 10 dpi in the virus-injected group. Nevertheless, in the poly (I:C)+virus-injected group, Mx and ISG15 expression were significantly expressed from 2 dpi. In summary, poly (I:C) administration in rock bream induces TLR3, IL1beta, Mx and ISG15-mediated immune responses, which could be a critical factor for inhibition of virus replication. PMID- 28986217 TI - A molluscan TNF receptor-associated factor 2 (TRAF2) was involved in host defense against immune challenges. AB - Tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2) is a member of the TRAF superfamily that acted as a key signal transduction protein and has been implicated in inflammatory and apoptosis processes in mammals. However, identification of TRAF2s in invertebrates is very limited and its function, in particular that under immune challenges, is still unknown. In this report, a molluscan TRAF2 gene (referred to as AwTRAF2) was cloned and characterized from the freshwater bivalve, Anodonta woodiana. The open reading frame (ORF) of AwTRAF2 was 1683 bp in length, which encoded a putative 560 amino acid-protein. The deduced AwTRAF2 sequence shared similar structural characteristics and close evolutionary relationship with mollusk TRAF2s. The tissue-specific expression analysis revealed that AwTRAF2 mRNA was broadly expressed in all tested tissues, with high expression in gill and hepatopancreas. In addition, in vivo injection experiments directly showed that AwTRAF2 mRNA levels in hepatopancreas were significantly up-regulated in response to bacterial pathogen (Vibrio alginolyticus and Staphylococcus aureus) and PAMPs (Lipopolysaccharides and Peptidoglycan) challenges. Moreover, fluorescence microscopy observations revealed that AwTRAF2 was mainly located in cytoplasm of HEK293T cells and its overexpression significantly increased the transcriptional activities of the NF kappaB-Luc reporter gene in HEK293T cells. Taken together, this study provided the experimental evidence of the presence of a functional TRAF2 in freshwater bivalves, which revealed its involvement in host response to immune challenges in A. woodiana. PMID- 28986218 TI - Molecular and expression analysis of the Allograft inflammatory factor 1 (AIF-1) in the coelomocytes of the common sea urchin Paracentrotus lividus. AB - Allograft inflammatory factor 1 (AIF-1) is a highly conserved gene involved in inflammation, cloned and characterized in several evolutionary distant animal species. Here, we report the molecular identification, characterization and expression of AIF-1 from the common sea urchin Paracentrotus lividus. In this species, AIF-1 encodes a predicted 151 amino acid protein with high similarity to vertebrate AIF-1 proteins. Immunocytochemical analyses on coelomocytes reveal localization of the AIF-1 protein in amoebocytes (perinuclear cytoplasmic zone) and red sphaerulocytes (inside granules), but not in vibratile cells and colorless sphaerula cells. The significant increase of AIF-1 expression (mRNA and protein) found in the coelomocytes of the sea urchin after Gram + bacterial challenge suggests the involvement of AIF-1 in the inflammatory response. Our analysis on P. lividus AIF-1 contributes to elucidate AIF-1 function along the evolutionary scale and consolidate the key evolutionary position of echinoderms throughout metazoans with respect to the common immune paths. PMID- 28986219 TI - The Pacific oyster (Crassostrea gigas) Hsp70 modulates the Ostreid herpes virus 1 infectivity. AB - The Ostreid herpes virus type 1 (OsHV-1) is one of the most devastating pathogen in oyster cultures. Among several factors, as food limitation, oxygen depletion, salinity and temperature variations, episodes of "summer mortality" of the Pacific oyster Crassostrea gigas have also been associated with OsHV-1 infection. Mortalities of C. gigas spat and juveniles have increased significantly in Europe, and contemporary mortality records of this mollusk in Mexico have been associated with the occurrence of OsHV-1. In the present study, the expression of the heat shock protein 70 gene from the Pacific oyster correlates with the abundance of DNA polymerase transcripts from the OsHV-1. This may suggest that the induction on the expression of the Pacific oyster hsp70 may potentially participate in the immune response against the virus. Furthermore, this study reports for the first time a TEM representative image of the OsHV-1 in aqueous solution, which possesses an icosahedral shape with a diameter of 70 nm * 100 nm. Finally, the examined sequence encoding the ORF4 of the OsHV-1 isolate from northwest Mexico showed specific sequence variations when compared with OsHV-1 isolates from distant geographical areas. PMID- 28986220 TI - Two mutations in mitochondrial ATP6 gene of ATP synthase, related to human cancer, affect ROS, calcium homeostasis and mitochondrial permeability transition in yeast. AB - The relevance of mitochondrial DNA (mtDNA) mutations in cancer process is still unknown. Since the mutagenesis of mitochondrial genome in mammals is not possible yet, we have exploited budding yeast S. cerevisiae as a model to study the effects of tumor-associated mutations in the mitochondrial MTATP6 gene, encoding subunit 6 of ATP synthase, on the energy metabolism. We previously reported that four mutations in this gene have a limited impact on the production of cellular energy. Here we show that two mutations, Atp6-P163S and Atp6-K90E (human MTATP6 P136S and MTATP6-K64E, found in prostate and thyroid cancer samples, respectively), increase sensitivity of yeast cells both to compounds inducing oxidative stress and to high concentrations of calcium ions in the medium, when Om45p, the component of porin complex in outer mitochondrial membrane (OM), was fused to GFP. In OM45-GFP background, these mutations affect the activation of yeast permeability transition pore (yPTP, also called YMUC, yeast mitochondrial unspecific channel) upon calcium induction. Moreover, we show that calcium addition to isolated mitochondria heavily induced the formation of ATP synthase dimers and oligomers, recently proposed to form the core of PTP, which was slower in the mutants. We show the genetic evidence for involvement of mitochondrial ATP synthase in calcium homeostasis and permeability transition in yeast. This paper is a first to show, although in yeast model organism, that mitochondrial ATP synthase mutations, which accumulate during carcinogenesis process, may be significant for cancer cell escape from apoptosis. PMID- 28986221 TI - The uL10 protein, a component of the ribosomal P-stalk, is released from the ribosome in nucleolar stress. AB - The ribosomal uL10 protein, formerly known as P0, is an essential element of the ribosomal GTPase-associated center responsible for the interplay with translational factors during various stages of protein synthesis. In eukaryotic cells, uL10 binds two P1/P2 protein heterodimers to form a pentameric P-stalk, described as uL10-(P1-P2)2, which represents the functional form of these proteins on translating ribosomes. Unlike most ribosomal proteins, which are incorporated into pre-ribosomal particles during early steps of ribosome biogenesis in the nucleus, P-stalk proteins are attached to the 60S subunit in the cytoplasm. Although the primary role of the P-stalk is related to the process of translation, other extraribosomal functions of its constituents have been proposed, especially for the uL10 protein; however, the list of its activities beyond the ribosome is still an open question. Here, by the combination of biochemical and advanced fluorescence microscopy techniques, we demonstrate that upon nucleolar stress induction the uL10 protein accumulates in the cytoplasm of mammalian cells as a free, ribosome-unbound protein. Importantly, using a novel approach, FRAP-AC (FRAP after photoConversion), we have shown that the ribosome free pool of uL10 represents a population of proteins released from pre-existing ribosomes. Taken together, our data indicate that the presence of uL10 on the ribosomes is affected in stressed cells, thus it might be considered as a regulatory element responding to environmental fluctuations. PMID- 28986222 TI - AUF1 modulates TGF-beta signal in renal tubular epithelial cells via post transcriptional regulation of Nedd4L expression. AB - Posttranscriptional regulation process plays important roles in renal disease pathogenesis. AU-rich element RNA-binding protein (AUF1) interacts with and destabilizes mRNAs containing AU-rich elements (AREs) in their 3'UTR. The current study demonstrated that AUF1 was increased in unilateral ureteral obstruction (UUO) animal models. While proliferation and migration of HK2 cells was unaltered by AUF1 downregulation under normal condition, proliferative inhibition and migratory promotion mediated by TGF-beta was significantly compromised. Mechanically, AUF1 downregulation decreased phosphorylated Smad2/3 via increasing their E3 ligase Nedd4L at the posttranscriptional level. In addition, the current study identified Nedd4L as a previously unreported target of AUF1. AUF1 regulates Nedd4L expression at the posttranscriptional level by interaction with AREs in the 3'UTR of the Nedd4L mRNA. Collectively, the current study indicates that AUF1 might be a potential player in renal tubulointerstitial fibrosis through modulation of TGF-beta signal transduction via posttranscriptional regulation of Nedd4L. PMID- 28986224 TI - Autophagy, Apoptosis, and Cell Proliferation in Exstrophy-Epispadias Complex. AB - OBJECTIVE: To investigate the state of autophagy and its interactions with apoptosis and cell proliferation in patients who underwent successful early closure or delayed closure of exstrophy. They compared those outcomes with cell culture samples from patients with vesicoureteral reflux as control. PATIENTS AND METHODS: Primary cultures of bladder smooth muscle cells (SMCs) were established from patients with successful neonatal bladder closure (group 1, N = 5), delayed closure because of small bladder template (group 2, N = 5), and vesicoureteral reflux as control (group 3, N = 5). The myogenicity of the cultures was determined using anti-Desmin antibody. Immunostainings for LC3 to assess autophagy and Ki67 to assess cell proliferation were applied. Apoptosis was assessed by the terminal deoxynucleotidyl transferase-mediated dUTP digoxigenin nick-end labeling assay. RESULTS: Autophagy marker (LC3) expression was significantly higher in the delayed closure group than in the other groups, whereas no significant difference was noted between the neonatal closure and the control groups. Apoptotic indices of the SMCs were remarkably higher in SMC cultures from the delayed closures than in the neonatal closure and the control groups. A significantly lower expression of proliferation marker (Ki67) in the delayed closure group compared with the control and the neonatal closure group was also of note. CONCLUSION: Patients with small bladder template and delayed closure showed upregulated autophagic process and increased apoptotic indices while experiencing a dramatic decrease in the proliferation of their bladder SMCs. Finally, the concept of manipulating autophagy may lead to promising outcomes for patients with bladder exstrophy in the future. PMID- 28986223 TI - Inflammatory response to mental stress and mental stress induced myocardial ischemia. AB - BACKGROUND: Mental stress-induced myocardial ischemia (MSIMI) is associated with increased risk of adverse cardiovascular outcomes, yet the underlying mechanisms are not well understood. We measured the inflammatory response to acute laboratory mental stress in patients with coronary artery disease (CAD) and its association with MSIMI. We hypothesized that patients with MSIMI would have a higher inflammatory response to mental stress in comparison to those without ischemia. METHODS: Patients with stable CAD underwent 99mTc sestamibi myocardial perfusion imaging during mental stress testing using a public speaking stressor. MSIMI was determined as impaired myocardial perfusion using a 17-segment model. Inflammatory markers including interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), matrix metallopeptidase 9 (MMP-9) and high-sensitivity C reactive protein (hsCRP) were measured at rest and 90 min after mental stress. Results were validated in an independent sample of 228 post-myocardial infarction patients. RESULTS: Of 607 patients analyzed in this study, (mean age 63 +/- 9 years, 76% male), 99 (16.3%) developed MSIMI. Mental stress resulted in a significant increase in IL-6, MCP-1, and MMP-9 (all p <0.0001), but not hsCRP. However, the changes in these markers were similar in those with and without MSIMI. Neither resting levels of these biomarkers, nor their changes with mental stress were significantly associated with MSIMI. Results in the replication sample were similar. CONCLUSION: Mental stress is associated with acute increases in several inflammatory markers. However, neither the baseline inflammatory status nor the magnitude of the inflammatory response to mental stress over 90 min were significantly associated with MSIMI. PMID- 28986225 TI - Pediatric Intracranial Aneurysms: Considerations and Recommendations for Follow Up Imaging. AB - BACKGROUND: Pediatric intracranial aneurysms (IAs) are rare. Compared with adult IAs, they are more commonly giant, fusiform, or dissecting. Treatment often proves more complex, and recurrence rate and de novo aneurysmogenesis incidence are higher. A consensus regarding the most appropriate algorithm for following pediatric IAs is lacking. METHODS: We sought to generate recommendations based on the reported experience in the literature with pediatric IAs through a thorough review of the PubMed database, discussion with experienced neurointerventionalists, and our own experience. RESULTS: Digital subtraction angiography (DSA) was utilized immediately post-operatively for microsurgically clipped and endovascularly-treated IAs, at 6-12 months postoperatively for endovascularly-treated IAs, and in cases of aneurysmal recurrence or de novo aneurysmogenesis discovered by non-invasive imaging modalities. Computed tomographic angiography was the preferred imaging modality for long-term follow up of microsurgically clipped IAs. Magnetic resonance angiography (MRA) was the preferred modality for following IAs that were untreated, endovascularly-treated, or microsurgically-treated in a manner other than clipping. CONCLUSIONS: We propose incidental untreated IAs to be followed by magnetic resonance angiography without contrast enhancement. Follow-up modality and interval for treated pediatric IAs is determined by initial aneurysmal complexity, treatment modality, and degree of posttreatment obliteration. Recurrence or de novo aneurysmogenesis requiring treatment should be followed by digital subtraction angiography and appropriate retreatment. Computed tomography angiography is preferred for clipped IAs, whereas contrast-enhanced magnetic resonance angiography is preferred for lesions treated endovascularly with coil embolization and lesions treated microsurgically in a manner other than clipping. PMID- 28986226 TI - Internal Carotid Artery and its Relationship with Structures in Sellar Region: Anatomic Study and Clinical Applications. AB - BACKGROUND: Complications of the internal carotid artery (ICA) in surgery are rare but severe. This study aimed to locate the ICA with 5 stationary bony structures in the sellar region: the anterior clinoid process, the tuberculum sellae, the bottom of the hypophyseal fossa, the posterior edge of the hypophyseal fossa, and the postclinoid process and to do measurements to determine their anatomic relationship with the ICA. METHODS: After multiple planar reconstructions on computer tomographic angiography images of 120 ICA in 60 individuals, we defined the 5 bony structures as 5 origins in the horizontal, sagittal, and vertical planes with the 3D coordinate system and got the cross sections of bilateral ICA on the coronal plane passing through each origin. We measured the distances between the cross-sections and the origins and angles between the horizontal plane and the line passing through the origin and the cross-sections on each coronal plane. We also measured the distances between the bilateral ICA on the 5 coronal planes. Besides, we measured the coordinate of the anterior edge of bilateral ICA, taking the anterior clinoid process as the origin. RESULTS: With the 3-dimensional coordinate system, we located the ICA to the bony structures in skull base. The distance between the bilateral ICA on coronal planes were 18.8 +/- 2.9 mm, 23.6 +/- 3.7 mm, 19.9 +/- 3.4 mm, 24.7 +/- 4.3 mm, and 23.5 +/- 3.5 mm, from anterior to posterior, respectively. CONCLUSION: The 3D coordinate system used in this study is of value in preoperational assessment, and data we obtained indicate the safety ranges avoiding damage to the ICA in surgery. PMID- 28986227 TI - Anterior Cervical Discectomy with Instrumented Allograft Fusion: Lordosis Restoration and Comparison of Functional Outcomes among Patients of Different Age Groups. AB - OBJECTIVE: To investigate clinical parameters of anterior cervical discectomy and fusion (ACDF) treatment and outcomes using osseous allografts in different age groups, study the postoperative results of restoration of lordosis, and evaluate the utility of bone allografts for ACDF, including graft subsidence. METHODS: We reviewed data from 154 patients with clinical symptoms and radiologic signs of disc herniation and/or cervical spondylosis. Decompression was achieved through discectomy, osteophyte ablation, endplate drilling, and foraminotomy. Fusion was achieved with allografts, demineralized bone matrix, and cervical plates/screws. The relationships between preoperative and postoperative cervical spine configuration (ie, Benzel's criteria), pain intensity, and neurologic status were analyzed. RESULTS: The mean patient age was 51 years, and the median duration of symptoms was 6 months. The mean age differed significantly between the patients with diabetes and those without diabetes. The mean body mass index (BMI) was 30.36. Fifty-two patients had disc herniation, and 102 had spondylosis. Surgery was performed on a total of 313 levels. The median duration of follow-up was 24 months. Marked improvements in postoperative spine configuration or preservation of lordosis were recorded. Overall, 122 patients were neurologically intact, and 32 patients experienced residual postsurgery neurologic deficits (minor, n = 22; moderate, n = 9; severe, n = 1). Postoperative pain intensity and neurologic status were significantly improved. Outcomes were excellent in 66 patients, good in 61, fair in 24, and poor in 3 (no mortality). No significant differences in patient age, smoking habits, diabetes, or BMI were seen among outcomes, or between patients with soft disc herniation or spondylosis. CONCLUSIONS: Osseous allografting can excellently restore cervical lordosis regardless of age and is an excellent graft choice for ACDF. Patients of advanced age with comorbidities should not be denied surgery. PMID- 28986228 TI - Application of Gelatin Sponge Impregnated with a Mixture of 3 Drugs to Intraoperative Nerve Root Block Combined with Robot-Assisted Minimally Invasive Transforaminal Lumbar Interbody Fusion Surgery in the Treatment of Adult Degenerative Scoliosis: A Clinical Observation Including 96 Patients. AB - OBJECTIVE: Application of nerve root block is mainly for diagnosis with less application in intraoperative treatment. The aim of this study was to observe clinical and imaging outcomes of application of gelatin sponge impregnated with a mixture of 3 drugs to intraoperative nerve root block combined with robot assisted minimally invasive transforaminal lumbar interbody fusion surgery in to treat adult degenerative lumbar scoliosis. METHODS: From January 2012 to November 2014, 108 patients with adult degenerative lumbar scoliosis were treated with robot-assisted minimally invasive transforaminal lumbar interbody fusion surgery combined with intraoperative gelatin sponge impregnated with a mixture of 3 drugs. Visual analog scale and Oswestry Disability Index scores were used to evaluate postoperative improvement of back and leg pain, and clinical effects were assessed according to the 36-Item Short-Form Health Survey. Imaging was obtained preoperatively, 1 week and 3 months postoperatively, and at the last follow-up. Fusion status, complications, and other outcomes were assessed. RESULTS: Follow-up was complete for 96 patients. Visual analog scale scores of leg and back pain on postoperative days 1-7 were decreased compared with preoperatively. At 1 week postoperatively, 3 months postoperatively, and last follow-up, visual analog scale score, Oswestry Disability Index score, coronal Cobb angle, and coronal and sagittal deviated distance decreased significantly (P = 0.000) and lumbar lordosis angle increased (P = 0.000) compared with preoperatively. Improvement rate of Oswestry Disability Index was 81.8% +/- 7.4. Fusion rate between vertebral bodies was 92.7%. CONCLUSIONS: Application of gelatin sponge impregnated with 3 drugs combined with robot-assisted minimally invasive transforaminal lumbar interbody fusion for treatment of adult degenerative lumbar scoliosis is safe and feasible with advantages of good short term analgesia effect, minimal invasiveness, short length of stay, and good long term clinical outcomes. PMID- 28986229 TI - Analysis of Survival Prognosis for Children with Symptomatic Optic Pathway Gliomas Who Received Surgery. AB - OBJECTIVE: The feasibility and prognosis of surgical treatment for children with optic pathway gliomas (OPGs) is controversial. Therefore this study attempted to evaluate the effects of surgery and discuss prognostic factors related to the survival of children with symptomatic OPGs. MATERIALS AND METHODS: One-hundred twenty-five children diagnosed with OPGs underwent surgery in the Department of Neurosurgery, Beijing Tiantan Hospital from 2003-2016. In this retrospective study, their demographics, clinical characteristics, treatments, and survival outcomes were investigated and summarized. RESULTS: Among the 125 patients, the 5 year overall survival (OS) rate and progression-free survival (PFS) rate were 84.1% and 70.6%, respectively. In the univariate analysis, patients who received postoperative radiotherapy (RT) after surgery had significantly better 5-year OS and PFS rates than patients who did not receive RT (P < 0.001 for both comparisons), patients who were 3 years old had better PFS rates than younger patients (P < 0.001), and patients with endocrinology symptoms had significantly worse PFS rates than patients with other symptoms (P = 0.049). In the multiple regression analysis, postoperative treatment with RT and tumors with a lower pathologic grade were better predictors of OS. An age older than 3 years and postoperative treatment with RT were better predictors of PFS. CONCLUSIONS: Surgery is safe and feasible for children with large volumes of OPGs and symptoms of functional impairment and obstructive hydrocephalus. Furthermore, adjuvant RT after surgery may significantly improve OS and PFS. The pathologic grade is an independent prognostic factor for OS, and the age at diagnosis is an independent prognostic factor for PFS. PMID- 28986230 TI - Machine Learning and Neurosurgical Outcome Prediction: A Systematic Review. AB - OBJECTIVE: Accurate measurement of surgical outcomes is highly desirable to optimize surgical decision-making. An important element of surgical decision making is identification of the patient cohort that will benefit from surgery before the intervention. Machine learning (ML) enables computers to learn from previous data to make accurate predictions on new data. In this systematic review, we evaluate the potential of ML for neurosurgical outcome prediction. METHODS: A systematic search in the PubMed and Embase databases was performed to identify all potential relevant studies up to January 1, 2017. RESULTS: Thirty studies were identified that evaluated ML algorithms used as prediction models for survival, recurrence, symptom improvement, and adverse events in patients undergoing surgery for epilepsy, brain tumor, spinal lesions, neurovascular disease, movement disorders, traumatic brain injury, and hydrocephalus. Depending on the specific prediction task evaluated and the type of input features included, ML models predicted outcomes after neurosurgery with a median accuracy and area under the receiver operating curve of 94.5% and 0.83, respectively. Compared with logistic regression, ML models performed significantly better and showed a median absolute improvement in accuracy and area under the receiver operating curve of 15% and 0.06, respectively. Some studies also demonstrated a better performance in ML models compared with established prognostic indices and clinical experts. CONCLUSIONS: In the research setting, ML has been studied extensively, demonstrating an excellent performance in outcome prediction for a wide range of neurosurgical conditions. However, future studies should investigate how ML can be implemented as a practical tool supporting neurosurgical care. PMID- 28986231 TI - Microsphere Embolization of Hypervascular Posterior Fossa Tumors. AB - BACKGROUND: Preoperative embolization of highly vascular tumors of the posterior fossa can decrease morbidity and operative blood loss. No clear consensus exists for the embolization agent of choice for optimal devascularization of these tumors. The purpose of this study was to assess effectiveness of microsphere embolization in reducing tumor hypervascularity before surgical resection. METHODS: We retrospectively reviewed medical records of patients with hypervascular posterior fossa tumors who were treated at a single institution from 2009 to 2016. RESULTS: Four of 9 patients with hypervascular posterior fossa tumors underwent embolization with 300-500 MUm microspheres before surgical resection. Patients selected for embolization had large tumors with large feeding vessels evident on brain magnetic resonance imaging. Surgical resection was performed within 24 hours of embolization in all 4 patients. Mean (SD) patient age was 42.5 years (18.4), and mean (SD) tumor size was 4.3 cm (1.4) in greatest dimension. All patients presented with symptoms related to mass effect. Gross total tumor resection was achieved in all patients. There were no intraoperative complications related to the embolization or craniotomy; mean (SD) blood loss was 350 mL (208). CONCLUSIONS: Preoperative embolization with microspheres can effectively reduce vascularity of the hypervascular posterior fossa tumor bed. This technique helped achieve complete resection, particularly for patients with recurrence after previous resection. PMID- 28986232 TI - Rifampicin inhibits rotenone-induced microglial inflammation via enhancement of autophagy. AB - Mitochondrial and autophagic dysfunction, as well as neuroinflammation, are associated with the pathophysiology of Parkinson's disease (PD). Rotenone, an inhibitor of mitochondrial complex I, has been associated as an environmental neurotoxin related to PD. Our previous studies reported that rifampicin inhibited microglia activation and production of proinflammatory mediators induced by rotenone, but the precise mechanism has not been completely elucidated. BV2 cells were pretreated for 2h with rifampicin followed by 0.1MUM rotenone, alone or in combination with chloroquine. Here, we demonstrate that rifampicin pretreatment alleviated rotenone induced release of IL-1beta and IL-6, and its effects were suppressed when autophagy was inhibited by chloroquine. Moreover, preconditioning with 50MUM rifampicin significantly increased viability of SH-SY5Y cells cocultured with rotenone-treated BV2 cells in the transwell coculture system. Chloroquine partially abolished the neuroprotective effects of rifampicin pretreatment. Rifampicin pretreatment significantly reversed rotenone-induced mitochondrial membrane potential reduction and reactive oxygen species accumulation. We suggest that the mechanism for rifampicin-mediated anti inflammatory and antioxidant effects is the enhancement of autophagy. Indeed, the ratio of LC3-II/LC3-I in rifampicin-pretreated BV2 cells was significantly higher than that in cells without pretreatment. Fluorescence and electron microscopy analyses indicate an increase of lysosomes colocalized with mitochondria in cells pretreated with rifampicin, which confirms that the damaged mitochondria were cleared through autophagy (mitophagy). Taken together, the data provide further evidence that rifampicin exerts neuroprotection against rotenone-induced microglia inflammation, partially through the autophagy pathway. Modulation of autophagy by rifampicin is a novel therapeutic strategy for PD. PMID- 28986233 TI - No doubts about dementia advocacy. PMID- 28986234 TI - Effects of blood flow restricted exercise training on muscular strength and blood flow in older adults. AB - BACKGROUND: In young adults, blood flow restricted exercise (BFRE) at relatively low intensities can increase muscle strength as effectively as conventional high intensity training. Ischemic exercise can also increase collateral blood flow in skeletal muscle. However, the effects of chronic BFRE on muscle strength and blood flow in older adults remain unknown. The purpose of this study was to compare the effects of 4weeks of BFRE training on skeletal muscle strength and blood flow between young and older subjects and between older adults performing BFRE and conventional high intensity resistance exercise. METHODS: Maximum voluntary contraction (MVC), forearm girth, peak forearm blood flow (FBF) and forearm vascular conductance (FVC) were assessed before and after 4weeks of forearm resistance training with BFRE in older adults (O-BFRE, 63+/-1 y, n=9) and younger adults (Y-BFRE, 22+/-1 y, n=8) and with high intensity training at 75% maximum voluntary contraction in older adults (O-HI, 63+/-1 y, n=10). RESULTS: MVC increased in all groups (O-BFRE, 33.4+/-4.7 to 36.3+/-4.7kg; Y-BFRE, 37.2+/ 4.9 to 43.0+/-5.0kg; O-HI, 34.0+/-4.4 to 39.8+/-4.4kg; all p<0.05). Forearm girth increased in O-BFRE (26.3+/-1.1 to 26.7+/-1.1cm; p<0.05) and Y-BFRE (23.9+/-0.9 to 25.1+/-1.5cm; p<0.05) but not in O-HI (25.9+/-1.0 to 26.1+/-1.0cm; p=0.26). Peak forearm vascular conductance increased in Y-BFRE (0.190+/-0.016 to 0.311+/ 0.031units; p=0.01) but not in O-BFRE (0.157+/-0.024 to 0.193+/-0.029units; p=0.48) and O-HI (0.188+/-0.035 to 0.227+/-0.035units; p=0.18). CONCLUSION: These data suggest that chronic BFRE training is effective in increasing muscular strength, muscle size and vascularity in young adults but, in older adults, increases only muscular strength and size. Longer training durations or higher volumes may be required to evoke similar vascular adaptations in older adults. PMID- 28986235 TI - Alpha-synuclein, epigenetics, mitochondria, metabolism, calcium traffic, & circadian dysfunction in Parkinson's disease. An integrated strategy for management. AB - The motor deficits which characterise the sporadic form of Parkinson's disease arise from age-related loss of a subset of dopamine neurons in the substantia nigra. Although motor symptoms respond to dopamine replacement therapies, the underlying disease process remains. This review details some features of the progressive molecular pathology and proposes deployment of a combination of nutrients: R-lipoic acid, acetyl-l-carnitine, ubiquinol, melatonin (or receptor agonists) and vitamin D3, with the collective potential to slow progression of these features. The main nutrient targets include impaired mitochondria and the associated oxidative/nitrosative stress, calcium stress and impaired gene transcription induced by pathogenic forms of alpha- synuclein. Benefits may be achieved via nutrient influence on epigenetic signaling pathways governing transcription factors for mitochondrial biogenesis, antioxidant defences and the autophagy-lysosomal pathway, via regulation of the metabolic energy sensor AMP activated protein kinase (AMPK) and the mammalian target of rapamycin mTOR. Nutrients also benefit expression of the transcription factor for neuronal survival (NR4A2), trophic factors GDNF and BDNF, and age-related calcium signals. In addition a number of non-motor related dysfunctions in circadian control, clock genes and associated metabolic, endocrine and sleep-wake activity are briefly addressed, as are late-stage complications in respect of cognitive decline and osteoporosis. Analysis of the network of nutrient effects reveals how beneficial synergies may counter the accumulation and promote clearance of pathogenic alpha-synuclein. PMID- 28986236 TI - Phylogeography of the endemic grasshopper genus Betiscoides (Lentulidae) in the South African Cape Floristic Region. AB - Vicariance and dispersal are two important processes shaping biodiversity patterns. The South African Cape Floristic Region (CFR) is known for its high biotic diversity and endemism. However, studies on the phylogeography of endemic invertebrates in this biodiversity hotspot are still scarce. Here, we present a phylogenetic study of the flightless grasshopper genus Betiscoides, which is endemic to the CFR and strongly associated with restio plants (Restionaceae). We hypothesized that the genus originated in the southwestern part of the CFR, that differentiation within the genus is mainly an effect of vicariance and that the three known species only represent a minor fraction of the real genetic diversity of the genus. We inferred the phylogeny based on sequences of three mitochondrial and two nuclear genes from 99 Betiscoides specimens collected across the CFR. Furthermore, we conducted a SDIVA analysis to detect distributions of ancestral nodes and the possible spatial origin of these lineages. Strong differentiation among genetic lineages was shown. The ancestor of this genus was most likely distributed in the southwestern CFR. Five major lineages were detected, three of which were ancestrally distributed in the southwestern CFR. The ancestors of the two other lineages were distributed in the northern and eastern margins of the CFR. A total of 24 divergent evolutionary lineages were found, reflecting the geographical isolation of restio-dominated fynbos habitats. Dispersal played a more prominent role than expected in differentiation of Betiscoides. While the five main lineages were separated during a first phase via dispersal, differentiation occurred later and on smaller spatial scale, predominantly driven by isolation in montane refugia (i.e. vicariance). Our study also suggests that flightless insect taxa likely show high levels of differentiation in biodiversity hotspots with their taxonomy often being incomplete. PMID- 28986237 TI - Compositional heterogeneity in true bug mitochondrial phylogenomics. AB - Mitochondrial phylogenomics is often controversial, in particular for inferring deep relationships. The recent rapid increase of mitochondrial genome data provides opportunities for better phylogenetic estimates and assessment of potential biases resulting from heterogeneity in nucleotide composition and mutation rates. Here, we gathered 76 mitochondrial genome sequences for Heteroptera representing all seven infraorders, including 17 newly sequenced mitochondrial genomes. We found strong heterogeneity in base composition and contrasting evolutionary rates among heteropteran mitochondrial genomes, which affected analyses with various datasets and partitioning schemes under site homogeneous models and produced false groupings of unrelated taxa exhibiting similar base composition and accelerated evolutionary rates. Bayesian analyses using a site-heterogeneous mixture CAT+GTR model showed high congruence of topologies with the currently accepted phylogeny of Heteroptera. The results confirm the monophyly of the six infraorders within Heteroptera, except for Cimicomorpha which was recovered as two paraphyletic clades. The monophyly of Terheteroptera (Cimicomorpha and Pentatomomorpha) and Panheteroptera (Nepomorpha, Leptopodomorpha and Terheteroptera) was recovered demonstrating a significant improvement over previous studies using mitochondrial genome data. Our study shows the power of the site-heterogeneous mixture models for resolving phylogenetic relationships with Heteroptera and provides one more case showing that model adequacy is critical for accurate tree reconstruction in mitochondrial phylogenomics. PMID- 28986238 TI - Origin and distribution of desert ants across the Gibraltar Straits. AB - The creation of geographic barriers has long been suspected to contribute to the formation of new species. We investigated the phylogeography of desert ants in the western Mediterranean basin in order to elucidate their mode of diversification. These insects which have a low dispersal capacity are recently becoming important model systems in evolutionary studies. We conducted an extensive sampling of species belonging to the Cataglyphis albicans group in the Iberian Peninsula (IP) and the northern Morocco (North Africa; NA). We then combined genetic, chemical and morphological analyses. The results suggest the existence of at least three and five clades in the IP and NA, respectively, whose delineation partially encompass current taxonomic classification. The three Iberian clades are monophyletic, but their origin in NA is uncertain (79% and 22% for Bayesian and Maximum Likelihood support, respectively). The estimation of divergence time suggests that a speciation process was initiated after the last reopening of the Gibraltar Straits ~5.33 Ma. In the IP, the clades are parapatric and their formation may have been triggered by the fragmentation of a large population during the Pleistocene due to extended periods of glaciation. This scenario is supported by demographic analyses pointing at a recent expansion of Iberian populations that contrasts with the progressive contraction of the NA clades. Niche modeling reveals that this area, governed by favorable climatic conditions for desert ants, has recently increased in the IP and decreased in NA. Altogether, our data points at geoclimatic events as major determinants of species formation in desert ants, reinforcing the role of allopatric speciation. PMID- 28986239 TI - Characterization and overexpression of a glycosyl hydrolase family 16 beta agarase YM01-1 from marine bacterium Catenovulum agarivorans YM01T. AB - Agar, usually extracted from seaweed, has a wide variety of industrial applications due to its gelling and stabilizing characteristics. Agarases are the enzymes which hydrolyze agar into agar oligosaccharides. The produced agar oligosaccharides have been widely used in cosmetic, food, and medical fields due to their biological functions. A beta-agarase gene, YM01-1, was cloned and expressed from a marine bacterium Catenovulum agarivorans YM01T. The encoding agarase of YM01-1 consisted of 331 amino acids with an apparent molecular mass of 37.7 kDa and a 23-amino-acids signal peptide. YM01-1 belongs to glycoside hydrolase 16 (GH16) family based on the amino acid sequence homology. The optimum pH and temperature for its activity was 7.0 and 50 degrees C, respectively. YM01 1 was stable at a pH of pH 6.0-9.0 and temperatures below 45 degrees C. Thin layer chromatography (TLC) and ion trap mass spectrometer of the YM01-1 hydrolysis products displayed that YM01-1 was an endo-type beta-agarase and degrades agarose, neoagarohexaose, neoagarotetraose into neoagarobiose. The Km, Vmax, Kcat and Kcat/Km values of the YM01-1 for agarose were 8.69 mg/ml, 4.35 * 103 U/mg, 2.4 * 103 s-1 and 2.7 * 106 s-1 M-1, respectively. Hence, the enzyme with high agarolytic activity and single end product was different from other GH16 agarases, which has potential applications for the production of oligosaccharides with remarkable activities. PMID- 28986240 TI - Cloning, overexpression, and purification of glucose-6-phosphate dehydrogenase of Pseudomonas aeruginosa. AB - Glucose-6-phosphate dehydrogenase (G6PDH) (EC 1.1.1.363) plays an important role in the human pathogen Pseudomonas aeruginosa because it generates NADPH, an essential cofactor for several biosynthetic pathways and antioxidant enzymes. P. aeruginosa G6PDH is also a key enzyme in the metabolism of various carbon sources, such as glucose, glycerol, fructose, and mannitol. Understanding the kinetic characteristics and mechanisms that control the activity of this enzyme is crucial for future studies in this context. However, one of the impediments to achieving this goal is the limited amount of protein obtained when current purification protocols are implemented, a factor curtailing its biochemical characterization. In this study, we report a fast, efficient and reproducible procedure for the purification of P. aeruginosa G6PDH that can be implemented in a short period (2 days). In order to establish this protocol, the zwf gene, which encodes for this enzyme, was cloned and overexpressed in Escherichia coli cells. In contrast to other procedures, our method is based on protein precipitation with CaCl2 and further purification by ion exchange chromatography. Using this protocol, we were able to obtain 31 mg/L of pure protein that manifested specific activity of 145.7 U/mg. The recombinant enzyme obtained in this study manifested similar physicochemical and kinetic properties to those reported in previous works for this molecule. The large quantities of active enzyme obtained using this procedure will facilitate its structural characterization and identify differences between P. aeruginosa- and human G6PDH, thus contributing to the search for selective inhibitors against the bacterial enzyme. PMID- 28986241 TI - To increase the incorporation efficiency of genetically encoding Nepsilon acetyllysine in recombinant protein. AB - Reversible Nepsilon-lysine (Nepsilon-Lys) acetylation is a dynamic post translational modification. Genetic incorporation of Nepsilon-acetyllysine (Nepsilon-AcK) into the specific site of a protein is a powerful method for producing recombinant protein with acetylation and studying the functional role of protein acetylation. Because of the universal existence of deacetylase such as CobB in vivo, the acetyl group of Nepsilon-AcK may be removed from recombinant protein. So in the process of incorporating acetyl lysine into protein, nicotinamide (NAM), a lysine deacetylase (KDAC) inhibitor, is needed to inhibit the KDAC activity and protect the acetyl group of Nepsilon-acetyllysine incorporated from removal in vivo. In this study, we knocked out cobB gene from an E. coli strain and used it as host for incorporating of Nepsilon-AcK into recombinant protein by expanding genetic code. Comparing with the addition of KDAC inhibitor, this is a novel method to protect the acetyl group of Nepsilon acetyllysine from deacetylation by using cobB knockout strain. Thus, this method provides a better way for protecting recombinant acetylated protein from deacetylation. By knocking out cobB gene from the strain of E. coli, we successfully produced homogeneous acetylated protein by expanding genetic code with a high effectiveness. This method will also provide a good reference for genetically introducing other varieties of modified amino acids into protein. PMID- 28986242 TI - An alternative approach identified optimal risk thresholds for treatment indication: an illustration in coronary heart disease. AB - OBJECTIVES: Treatment thresholds based on risk predictions can be optimized by considering various health (economic) outcomes and performing marginal analyses, but this is rarely performed. We demonstrate a general approach to identify treatment thresholds optimizing individual health (economic) outcomes, illustrated for statin treatment based on 10-year coronary heart disease (CHD) risk predicted by the Framingham risk score. STUDY DESIGN AND SETTING: Creating a health economic model for a risk-based prevention strategy, risk thresholds can be evaluated on several outcomes of interest. Selecting an appropriate threshold range and decrement size for the thresholds and adapting the health economic model accordingly, outcomes can be calculated for each risk threshold. A stepwise, or marginal, comparison of clinical as well as health economic outcomes, that is, comparing outcomes using a specific threshold to outcomes of the former threshold while gradually lowering the threshold, then takes into account the balance between additional numbers of individuals treated and their outcomes (additional health effects and costs). In our illustration, using a Markov model for CHD, we evaluated risk thresholds by gradually lowering thresholds from 20% to 0%. RESULTS: This approach can be applied to identify optimal risk thresholds on any outcome, such as to limit complications, maximize health outcomes, or optimize cost-effectiveness. In our illustration, keeping the population-level fraction of statin-induced complications <10% resulted in thresholds of T = 6% (men) and T = 2% (women). Lowering the threshold and comparing quality-adjusted life-years (QALYs) after each 1% decrease, QALYs were gained down to T = 1% (men) and T = 0% (women). Also accounting for costs, net health benefits were favorable down to T = 3% (men) and T = 6% (women). CONCLUSION: Using a stepwise risk-based approach to threshold optimization allows for preventive strategies that optimize outcomes. Presenting this comprehensive overview of outcomes will better inform decision makers when defining a treatment threshold. PMID- 28986243 TI - Construction of an expression vector that uses the aph promoter for protein expression in Corynebacterium glutamicum. AB - Corynebacterium glutamicum is an attractive host for the production of heterologous proteins despite its traditional use in fermentative production of amino acids. To enhance the expression levels of target genes, the development of useful promoters is required in the construction of expression systems. Here, we developed a new promoter, the aph promoter from aminoglycoside-3' phosphotransferase gene, and used it to construct monocistronic and bicistronic expression systems that host different ribosome binding site (RBS) sequences. First, the expression level of the reporter protein, enhanced green fluorescent protein (EGFP), varied with changes in the RBS sequences in the constructed vectors. The results showed that the fluorescence intensities of the bicistronic group were higher than those of the monocistronic group and that RM3E showed the highest fluorescence intensity, which was 42-fold higher than the lowest (RA2E') among these groups. Next, taking advantage of the optimized aph promoter, we successfully employed this aph promoter for alpha-amylase and VHH (camelid antibody fragment) expression. The secretion of alpha-amylase improved 1.5-fold after promoter mutation. This promoter will be useful for heterologous protein production in C. glutamicum cells. PMID- 28986244 TI - Expression of recombinant alpha-toxin BmKM9 from scorpion Buthus martensii Karsch and its functional characterization on sodium channels. AB - Scorpion toxins are invaluable pharmacological tools for studying ion channels and potential drugs for channelopathies. The long-chain toxins from scorpion venom with four disulfide bridges exhibit their unusual bioactivity or biotoxicity by acting on the sodium channels. However, the functional properties of most toxins are still unclear due to their tiny amounts in crude venom and their challenging production by chemical and gene engineering techniques. Here, we expressed one of the long-chain alpha-toxins, BmKM9, found in the venom of the scorpion Buthus martensii Karsch and characterized its pharmacological properties on sodium channels. Unlike previous toxin production, the recombinant BmKM9 (rBmKM9) possessed no additional amino acid residues such as the His-tag and thrombin cleavage site. The refolded toxin could inhibit the inactivation of rNav1.4, hNav1.5 and hNav1.7 sodium channels. Dose-response experiments were further conducted on these channels. The calculated EC50 values were 131.7+/ 6.6nM for rNav1.4, 454.2+/-50.1nM for hNav1.5 and 30.9+/-10.3MUM for hNav1.7. The channel activation experiments indicated that the rBmKM9 toxin could shift the activation curves of rNav1.4 and hNav1.5 channels toward a more negative direction and present the typical features of a beta-toxin. However, instead of the same activation property on sodium channels, the rBmKM9 toxin could result in different inactivation shift capabilities on rNav1.4 and hNav1.5 channels. The V1/2 values of the steady-state inactivation were altered to be more positive for rNav1.4 and more negative for hNav1.5. Moreover, the recovery of the hNav1.5 channel from inactivation was more significantly delayed than that of the rNav1.4 channel by exposure to rBmKM9. Together, these findings highlighted that the rBmKM9 toxin presents the pharmacological properties of both alpha- and beta toxins, which would increase the challenge to the classical classification of scorpion toxins. Furthermore, the expression method and functional information on sodium channels would promote the potential application of toxins and contribute to further channel structural and functional studies. PMID- 28986246 TI - Sphingosine 1-phosphate alleviates Coxsackievirus B3-induced myocarditis by increasing invariant natural killer T cells. AB - Sphingosine 1-phosphate (S1P), via binding to its specific receptors of S1PR1, participates in the regulation of both innate and adaptive immunity. Recent reports have identified S1P as a messenger mediating inflammation. However, roles of S1P in Coxsackievirus B3 (CVB3)-induced myocarditis were largely unknown. Here, we investigated the effect of S1P treatment on CVB3-induced myocarditis in vivo. We found that CVB3 infection downregulated S1PR1 expression in spleen and decreased the proportion of invariant natural killer T cells (iNKT) in CD3 positive T cells both in spleen and in blood from left ventricle, which accompanied by severe inflammation lesions and more virus capsid protein (VP1) expression in heart tissue. In comparison, S1P supply upregulated iNKT in the spleen and in blood from left ventricle, which represented the strengthening of anti-inflammatory effects. Indeed, inflammation infiltration, VP1 expression and apoptosis in the myocardium was all downregulated. These results demonstrated that S1P supplement could alleviate CVB3-induced myocarditis. PMID- 28986245 TI - Applying Interactive Mobile health to Asthma Care in Teens (AIM2ACT): Development and design of a randomized controlled trial. AB - Early adolescents have difficulties performing asthma self-management behaviors, placing them at-risk for poor asthma control and reduced quality of life. This paper describes the development and plans for testing an interactive mobile health (mHealth) tool for early adolescents, ages 12-15years, and their caregivers to help improve asthma management. Applying Interactive Mobile health to Asthma Care in Teens (AIM2ACT) is informed by the Pediatric Self-management model, which posits that helpful caregiver support is facilitated by elucidating disease management behaviors and allocating treatment responsibility in the family system, and subsequently engaging in collaborative caregiver-adolescent asthma management. The AIM2ACT intervention was developed through iterative feedback from an advisory board composed of adolescent-caregiver dyads. A pilot randomized controlled trial of AIM2ACT will be conducted with 50 early adolescents with poorly controlled asthma and a caregiver. Adolescent-caregiver dyads will be randomized to receive the AIM2ACT smartphone application (AIM2ACT app) or a self-guided asthma control condition for a 4-month period. Feasibility and acceptability data will be collected throughout the trial. Efficacy outcomes, including family asthma management, lung function, adolescent asthma control, asthma-related quality of life, and self-efficacy for asthma management, will be collected at baseline, post-treatment, and 4-month follow-up. Results from the current study will inform the utility of mHealth to foster the development of asthma self-management skills among early adolescents. PMID- 28986247 TI - The reintroduction of DENV-2 in 2011 in Panama and subsequent outbreak characteristic. AB - The circulation of the South-east Asian/American (AS/AM) dengue 2 virus (DENV-2) genotype in the Americas has been associated with a high rate of severe disease. From 1993, the year DENV was reintroduced in Panama, until 2011 there were 29 dengue-associated deaths, 17 of which occurred in 2011, the most severe outbreak with a case fatality rate (CFR) of 44% (17 deaths out of 38 severe dengue cases). During this outbreak DENV-2 was reintroduced into the country, whereas over the prior five years DENV-1 and -3 were predominant. Herein, we describe the 2011 Panama outbreak and genetically characterize the Panamanian DENV-2 strains, which were associated with severe dengue disease in Panama. Our results suggest that the DENV-2 isolates from this outbreak belonged to the AS/AM genotype sub-clade 2BI and were genetically close to viruses described in the outbreaks in Nicaragua, Honduras, Guatemala and Mexico from 2006-2011. Sub-clade 2BI has previously been associated with severe disease in Nicaragua during outbreaks from 2005-2007. PMID- 28986249 TI - Presence of Borrelia spp. DNA in ticks, but absence of Borrelia spp. and of Leptospira spp. DNA in blood of fever patients in Madagascar. AB - The occurrence of tick-borne relapsing fever and leptospirosis in humans in Madagascar remains unclear despite the presence of their potential vectors and reservoir hosts. We screened 255 Amblyomma variegatum ticks and 148 Rhipicephalus microplus ticks from Zebu cattle in Madagascar for Borrelia-specific DNA. Borrelia spp. DNA was detected in 21 Amblyomma variegatum ticks and 2 Rhipicephalus microplus ticks. One Borrelia found in one Rhipicephalus microplus showed close relationship to Borrelia theileri based on genetic distance and phylogenetic analyses on 16S rRNA and flaB sequences. The borreliae from Amblyomma variegatum could not be identified due to very low quantities of present DNA reflected by high cycle threshold values in real-time-PCR. It is uncertain whether these low numbers of Borrelia spp. are sufficient for transmission of infection from ticks to humans. In order to determine whether spirochaete infections are relevant in humans, blood samples of 1009 patients from the highlands of Madagascar with fever of unknown origin were screened for Borrelia spp. - and in addition for Leptospira spp. - by real-time PCR. No target DNA was detected, indicating a limited relevance of these pathogens for humans in the highlands of Madagascar. PMID- 28986248 TI - The roles of galectins in parasitic infections. AB - Galectins is a family of multifunctional lectins. Fifteen galectins have been identified from a variety of cells and tissues of vertebrates and invertebrates. Galectins have been shown to play pivotal roles in host-pathogen interaction such as adhesion of pathogens to host cells and activation of host innate and adaptive immunity. In recent years, the roles of galectins during parasite infections have gained increasing attention. Galectins produced by different hosts can act as pattern recognition receptors detecting conserved pathogen-associated molecular patterns of parasites, while galectins produced by parasites can modulate host responses. This review summarizes some recent studies on the roles of galectins produced by parasitic protozoa, nematodes, and trematodes and their hosts. Understanding the roles of galectins in host-parasite interactions may provide targets for immune intervention and therapies of parasitic infections. PMID- 28986250 TI - A serum exosomal microRNA panel as a potential biomarker test for gastric cancer. AB - The findings from several studies have suggested that circulating miRNAs are imbalanced with the genesis of gastric cancer (GC). Both normal and cancer cells can generate and secrete exosomes, which are nanosized membrane vesicles that can transport microRNAs and proteins. Emerging evidence indicates that the exosomes secreted by cancer cells can be released into the circulatory system. In this study, we investigated whether circulating exosomal miRNAs can be used to discriminate individuals with GC from healthy controls (NCs). Based on the quantitative reverse transcription polymerase chain reaction (qRT-PCR), four miRNAs (miR-19b-3p, miR-17-5p, miR-30a-5p, and miR-106a-5p) related to GC pathogenesis were identified in serum-circulating exosomes from a cohort of 20 healthy controls and 20 individuals with GC in the initial screening phase. The distinguished miRNAs were further validated in the training (90 GC vs. 90 NCs) and blinded phases 20 GC vs. 20 NCs), and the area under receiver operating characteristic (ROC) curves of these miRNAs were analyzed. We found that miR-19b and miR-106a were markedly overexpressed in individuals with GC compared to NCs (P < 0.0001). Besides, the ROC analyses yielded the AUC values of 0.786 for miR 106a-5p, 0.769 for miR-19b-3p and combined ROC analysis revealed the highest AUC value of 0.814 in discriminating GC patients from NCs. Furthermore, based on the model developed from the data, a signature composed of the 2 miRNAs (miR-19b-3p and miR-106a-5p) correctly discriminated 19 out of 20 GC serum samples (95% sensitivity) and 18 out of 20 normal samples (90% specificity) in the blinded phase. Moreover, the validated miRNAs were related to GC lymphatic metastasis (P < 0.01) and expressed at higher levels in stages III and IV compared to I and II stages (P < 0.05). These results suggest that serum exosomal miR-19b-3p and miR 106a-5p are novel potential biomarkers for detecting GC. PMID- 28986251 TI - Fluorescent protein Dendra2 as a ratiometric genetically encoded pH-sensor. AB - Fluorescent protein Dendra2 is a monomeric GFP-like protein that belongs to the group of Kaede-like photoconvertible fluorescent proteins with irreversible photoconversion from a green- to red-emitting state when exposed to violet-blue light. In an acidic environment, photoconverted Dendra2 turns green due to protonation of the phenolic group of the chromophore with pKa of about 7.5. Thus, photoconverted form of Dendra2 can be potentially used as a ratiometric pH-sensor in the physiological pH range. However, incomplete photoconversion makes ratiometric measurements irreproducible when using standard filter sets. Here, we describe the method to detect fluorescence of only photoconverted Dendra2 form, but not nonconverted green Dendra2. We show that the 350 nm excitation light induces solely the fluorescence of photoconverted protein. By measuring the red to green fluorescence ratio, we determined intracellular pH in live CHO and HEK 293 cells. Thus, Dendra2 can be used as a novel ratiometric genetically encoded pH sensor with emission maxima in the green-red spectral region, which is suitable for application in live cells. PMID- 28986252 TI - Uric acid demonstrates neuroprotective effect on Parkinson's disease mice through Nrf2-ARE signaling pathway. AB - Uric acid has neuroprotective effect on Parkinson's disease (PD) by inhibiting oxidative damage and neuronal cell death. Our previous study has shown that uric acid protected dopaminergic cell line damage through inhibiting accumulation of NF-E2-related factor 2 (Nrf2). This study aimed to investigate its in vivo neuroprotective effect. PD was induced by MPTP intraperitoneally injection for 7 d in male C57BL/6 mice. Mice were treated with either uric acid (intraperitoneally injection 250 mg/kg) or saline for a total of 13 d. We showed that uric acid improved behavioral performances and cognition of PD mice, increased TH-positive dopaminergic neurons and decreased GFAP-positive astrocytes in substantia nigra (SN). Uric acid increased mRNA and protein expressions of Nrf2 and three Nrf2-responsive genes, including gamma-glutamate-cysteine ligase catalytic subunit (gamma-GCLC), heme oxygenase-1 (HO-1) and NQO1. Uric acid significantly increased superoxide dismutase (SOD), CAT, glutathione (GSH) levels and decreased malondialdehyde (MDA) level in SN regions of MPTP-treated mice. Uric acid inhibited the hippocampal expression of IL-1beta and decreased serum and hippocampus levels of interleukin-1beta (IL-1beta), IL-6 and tumor necrosis factor-alpha (TNF-alpha). In conclusion, uric acid demonstrates neuroprotective properties for dopaminergic neurons in PD mice through modulation of neuroinflammation and oxidative stress. PMID- 28986253 TI - miR-19 promotes osteosarcoma progression by targeting SOCS6. AB - microRNAs (miRNAs) play critical roles in cancer development and progression. This study investigated the effects of miR-19 in human osteosarcoma (OS) development. Here, we showed that miR-19 was frequently upregulated in OS tissues and cell lines. Moreover the expression of miR-19 was associated with TNM stage, metastasis, size and poor overall survival. Mechanistically, miR-19 dramatically suppressed OS growth in vitro and in vivo. Bioinformatics analyses predicted that SOCS6 is a potential target gene of miR-19 in OS, which was confirmed by luciferase-reporter assay. We also found that SOCS6 expression was downregulated and negatively correlated with miR-19 expression in OS tissues clinically. Moreover, ectopic SOCS6 could reverse miR-19 induced OS growth. Finally, JAK2/STAT3 signaling pathway involves miR-19/SOCS6-mediated OS progression. Together, our data provide important evidence for miR-19 mediated SOCS6 in OS growth and revealed miR-19/SOCS6/JAK2/STAT3 pathway as a potential therapeutic strategy for OS patients. PMID- 28986254 TI - Enhanced stability of kinesin-1 as a function of temperature. AB - Kinesin-1 is a mechanochemical enzyme which mediates long distance intracellular cargo transport along microtubules in a wide variety of eukaryotic cells. Kinesin is also relatively easy to purify and shows robust function in vitro, leading to numerous proposals for using the kinesin-1/microtubule system for nanoscale transport in engineered devices. However, kinesin in vitro shows signs of degradation at ~30 degrees C which severely limits its usability in biomimetic engineering. Notably, kinesin-1 functions robustly in animal cells at body temperatures as high as 40 degrees C which suggests that kinesin functioning can be stabilized beyond what is observed in vitro. The present study investigated the effect of trimethylamine N-oxide (TMAO) as a potential heat-protecting agent for kinesin function and microtubule stability. We show that at a concentration of 200 mM, TMAO can indeed stabilize kinesin-based motility up to a little over 50 degrees C and that such motility can be sustained for extended periods of time. Our results suggest that intracellular crowding (mimicked in vitro by TMAO) can indeed stabilize kinesin-1 at high temperatures and helps resolve a long standing discrepancy between thermal stability of kinesin-1 observed in vivo and in vitro. Moreover, when considered together with our previous report that kinesin-1 can function well down to near-freezing conditions, this study establishes kinesin-1/microtubule motility as a thermally viable engineering platform. PMID- 28986255 TI - Down regulation of Peroxiredoxin-3 in 3T3-L1 adipocytes leads to oxidation of Rictor in the mammalian-target of rapamycin complex 2 (mTORC2). AB - Mitochondrially-derived oxidative stress has been implicated in the development of obesity-induced insulin resistance and is correlated with down regulation of Peroxiredoxin-3 (Prdx3). Prdx3 knockout mice exhibit whole-body insulin resistance, while Prdx3 transgenic animals remain insulin sensitive when placed on a high fat diet. To define the molecular events linking mitochondrial oxidative stress to insulin action, Prdx3 was silenced in 3T3-L1 adipocytes (Prdx3 KD) and the resultant cells evaluated for mitochondrial function, endoplasmic reticulum stress (ER stress), mitochondrial unfolded protein response (mtUPR) and insulin signaling. Prdx3 KD cells exhibit a two-fold increase in H2O2, reduced insulin-stimulated glucose transport and attenuated S473 phosphorylation of the mTORC2 substrate, Akt. Importantly, the decrease in glucose uptake can be rescued by pre-treatment with the antioxidant N-acetyl cysteine (NAC). The changes in insulin sensitivity occur independently from activation of the ER stress or mtUPR pathways. Analysis of mTORC2, the complex responsible for phosphorylating Akt at S473, reveals increased cysteine oxidation of Rictor in Prdx3 KD cells that can be rescued with NAC. Taken together, these data suggest mitochondrial dysfunction in adipocytes may attenuate insulin signaling via oxidation of the mammalian-target of rapamycin complex 2 (mTORC2). PMID- 28986256 TI - MicroRNA-7 inhibits cell proliferation of chronic myeloid leukemia and sensitizes it to imatinib in vitro. AB - MicroRNA is a large class of non-coding small RNA that exerts critical roles in many physiological processes including cell proliferation. MicroRNA-7 (miR-7) has been considered as a tumor suppressor in most malignant tumors versus a tumor promoter in some other ones. However, its role in chronic myeloid leukemia remains unknown. Herein, we found that K562 cell proliferation was largely suppressed when it was stably transfected with miR-7. In accordance with that, apoptosis was also significantly upregulated in miR-7 stably-transfected K562 cells. Moreover, we found that miR-7-overexpressed K562 cells were far more sensitive to imatinib than controls. Further investigations showed that the ABL1 was a direct target of miR-7. Expression level of BCR-ABL and the activity of its downstream PI3K/AKT pathway were significantly reduced in miR-7-transfected cells. Taken together, our results showed that miR-7 inhibited proliferation and promoted apoptosis in K562 cells, and miR-7 might help to sensitize them to imatinib through BCR-ABL/PI3K/AKT signaling in chronic myeloid leukemia. PMID- 28986257 TI - Ecm22 and Upc2 regulate yeast mating through control of expression of the mating genes PRM1 and PRM4. AB - Budding yeast mating is an excellent model for receptor-activated cell differentiation. Here we identify the related transcription factors Ecm22 and Upc2 as novel regulators of mating. Cells lacking both ECM22 and UPC2 display strong mating defects whereas deletion of either gene has no effect. Ecm22 and Upc2 positively regulate basal expression of PRM1 and PRM4. These genes are strongly induced in response to mating pheromone, which is also largely dependent on ECM22 and UPC2. We further show that deletion of PRM4 like PRM1 results in markedly reduced mating efficiency. Expression of PRM1 but not of PRM4 is also regulated by Ste12, a key transcription factor for mating. STE12 deletion lowers basal PRM1 expression, whereas STE12 overexpression strongly increases PRM1 levels. This regulation of PRM1 transcription is mediated through three Ste12 binding sites in the PRM1 promoter. Simultaneous deletion of ECM22 and UPC2 as well as mutation of the three Ste12-binding sites in the PRM1 promoter completely abolishes basal and pheromone-induced PRM1 expression, indicating that Ste12 and Ecm22/Upc2 control PRM1 transcription through distinct pathways. In summary, we propose a novel mechanism for budding yeast mating. We suggest that Ecm22 and Upc2 regulate mating through the induction of the mating genes PRM1 and PRM4. PMID- 28986258 TI - Fractalkine/CX3CR1 axis modulated the development of pancreatic ductal adenocarcinoma via JAK/STAT signaling pathway. AB - Pancreatic ductal adenocarcinoma (PDAC) is a fatal malignancy with an estimated 5 year survival rate of approximately 5% of all stages combined. High potential of PDAC metastasis is a leading cause for high mortality and poor prognosis. The majority of patients present with distant metastasis at diagnosis. Fractalkine (FKN) is recognized as a chemokine and a specific ligand of CX3CR1. It has been reported that FKN/CX3CR1 system was upregulated in many types of solid tumors. However, role of FKN/CX3CR1 in PDAC development remains unclear. In the current investigation, we found that FKN and CX3CR1 expression was significantly increased in PDAC tissues, especially in the metastatic samples, and was highly correlated with severity of PDAC. Ectopic expression of FKN promoted the proliferation and migration of PDAC, while knockdown of CX3CR1 reversed the function of FKN. In addition, PDAC cells with FKN-deficiency showed impaired proliferation and migration activity. The underlying mechanism is that FKN/CX3CR1 activated JAK/STAT signaling, which in turn regulated cell growth. Consistently, in vivo tumorigenesis assay validated the regulatory role of FKN/CX3CR1 in PDAC growth. Our investigation helped understanding the pathogenesis of PDAC occurrence, and demonstrated critical role of FKN/CX3CR1 in PDAC development. PMID- 28986259 TI - Inhibition of constitutive NF-kappaB activity induces platelet apoptosis via ER stress. AB - Platelets are anucleate cells, known for their pivotal roles in hemostasis, inflammation, immunity, and disease progression. Being anuclear, platelets are known to express several transcriptional factors which exert nongenomic functions, including the positive and negative regulation of platelet activation. NF-kappaB is one such transcriptional factor involved in the regulation of genes for survival, proliferation, inflammation and immunity. Although, the role NF kappaB in platelet activation and aggregation is partially known, its function in management of platelet survival and apoptosis remain unexplored. Therefore, two unrelated inhibitors of NF-kappaB activation, BAY 11-7082 and MLN4924 were used to determine the role of NF-kappaB in platelets. Inhibition of NF-kappaB caused decreased SERCA activity and increased cytosolic Ca2+ level causing ER stress which was determined by the phosphorylation of eIF2-alpha. Further, there was increased BAX and decreased BCl-2 levels, incidence of mitochondrial membrane potential depolarization, release of cytochrome c into cytosol, caspase activation, PS externalization and cell death in BAY 11-7082 and MLN4924 treated platelets. The obtained results demonstrate the critical role played by NF-kappaB in Ca2+ homeostasis and survival of platelets. In addition, the study demonstrates the potential side effects associated with NF-kappaB inhibitors employed during inflammation and cancer therapy. PMID- 28986260 TI - Isothermal titration calorimetry and vesicle leakage assays highlight the differential behaviors of tau repeat segments upon interaction with anionic lipid membranes. AB - Tau misfolding has been implicated in a variety of tauopathies, including Alzheimer's disease. The microtubule binding domain of tau consists of four repeat segments (R1-R4), and aggregation of these segments leads to the formation of neurofibrillary tangles. Previous studies indicate that misfolded tau associates with anionic phospholipid membranes, invoking structural transformations that could play a role in aggregation. Here, we investigated the role of membrane surface charge on the binding affinity of individual tau repeat segments, and whether these segments exhibit lytic activity. We quantified the thermodynamics of this process in terms of the affinity (Kd), enthalpy (DeltaH), entropy (DeltaS), and change in specific heat capacity (DeltaCp). While neutral membranes exhibited weak interactions with each tau repeat segment, segments R2 and R3 exhibited relatively strong binding with anionic membranes with favorable DeltaS and a negative value of DeltaCp. Calcein leakage assays show that each repeat segment displays lytic activity, but only upon the interaction with anionic membranes. Taken together, these results distinguish the relative selectivity for anionic membranes by each repeat segment and the degree of membrane disruption that results. PMID- 28986261 TI - MMP-9-cleaved osteopontin isoform mediates tumor immune escape by inducing expansion of myeloid-derived suppressor cells. AB - As an extracellular matrix protein, osteopontin (OPN) has been shown to play an important role in regulation of the immune response to tumors. Myeloid-derived suppressor cells (MDSCs), a heterogeneous population of myeloid progenitors, are major components of the immune suppressive tumor microenvironment and contribute to tumor evasion of the immune response. However, the specific regulating mechanisms underlying MDSCs expansion remain unclear. Here, we found that MDSCs accumulated in the spleen and tumors of 3LL tumor-bearing mice. Supernatant collected from 3LL cells was able to induce the expansion of MDSCs in peripheral blood mononuclear cell (PBMC) in vitro. Results of enzyme linked immunosorbent assay showed high levels of OPN and matrix metalloproteinase-9 (MMP-9) in this supernatant. Silencing OPN can effectively reduce MDSCs frequency in vivo and in vitro. Furthermore, a specific fragment of OPN, OPN-32 kDa cleaved by MMP-9 was detected in the supernatant from 3LL cells. Overexpression of OPN-32 kDa in 3LL cells induced MDSCs expansion. Inhibition of MMP-9 by monoclonal antibody and inhibitor (TIMP-1) reduced MDSCs expansion in vitro and in vivo. These findings suggest that the MMP-9-cleaved OPN fragment, OPN-32kDa, was responsible for MDSCs expansion, which may contribute to tumor's evasion of the immune response. PMID- 28986263 TI - Flavonoid and stilbene derivatives from Macaranga trichocarpa. AB - A new farnesylated flavonol (4'-O-methylmacagigantin) and a new geranylated stilbene (macatrichocarpin H), together with eight known phenolic compounds, have been isolated from the leaves of Macaranga trichocarpa. Structures of these compounds were determined based on NMR and mass spectrroscopic data. Cytotoxic properties of the isolated compounds were tested against P-388 cells showing that mactrichocarpin G was the most active compound with IC50 was 3.5MUM. PMID- 28986264 TI - Sulfated neo-clerodane diterpenoids and triterpenoid saponins from Sheareria nana S. Moore. AB - Three novel neo-clerodane diterpenoids Sheareria A-C (1-3) together with three known triterpenoid saponins were isolated from the whole herb of Sheareria nana S. Moore. Their structures were established by spectroscopic and chemical method. This is the first natural sulfated neo-clerodane diterpenoids. This is the first report of all these compounds from this plant. These neo-clerodane diterpenoids and triterpenoid saponins from S. nana S. Moore may be considered as chemotaxonomic markers for the genus. The compounds isolated were evaluated for their cytotoxic effects against three cancer cell lines, the test substances demonstrated selectivity toward the cancer cells. To date, this is the first report on the phytochemical and biological activity of secondary metabolites from S. nana S. Moore. PMID- 28986262 TI - A simple elution strategy for biotinylated proteins bound to streptavidin conjugated beads using excess biotin and heat. AB - Protein-protein interactions are the molecular basis of cell signaling. Recently, proximity based biotin identification (BioID) has emerged as an alternative approach to traditional co-immunoprecipitation. In this protocol, a mutant biotin ligase promiscuously labels proximal binding partners with biotin, and resulting biotinylated proteins are purified using streptavidin conjugated beads. This approach does not require preservation of protein complexes in vitro, making it an ideal approach to identify transient or weak protein complexes. However, due to the high affinity bond between streptavidin and biotin, elution of biotinylated proteins from streptavidin conjugated beads requires harsh denaturing conditions, which are often incompatible with downstream processing. To effectively release biotinylated proteins bound to streptavidin conjugated beads, we designed a series of experiments to determine optimal binding and elution conditions. Interestingly, the concentrations of SDS and IGEPAL-CA630 during the incubation with streptavidin conjugated beads were the key to effective elution of biotinylated proteins using excess biotin and heating. This protocol provides an alternative method to isolate biotinylated proteins from streptavidin conjugated beads that is suitable for further downstream analysis. PMID- 28986265 TI - Risk of advanced colorectal neoplasm by the proposed combined United States and United Kingdom risk stratification guidelines. AB - BACKGROUND AND AIMS: The U.K. guidelines for risk stratification after colon polypectomy differ from the U.S. guidelines in 2 ways: the U.K. guidelines consider >=5 adenomas as high risk and do not consider histology (villous or high grade dysplasia) in the assessment. Thus, we aimed to investigate the risk of advanced colorectal neoplasm (CRN) by categorized risk groups, considering both >=5 adenomas and histology. METHODS: A total of 2570 patients with >=1 adenoma at index colonoscopy were included. The patients were divided into 6 groups: group 1, 1 to 2 non-advanced adenomas (non-AAs) >=10 mm or high-grade dysplasia or villous adenoma; group 1A, 1 to 2 adenomas with >=1 advanced adenoma (AA); group 2, 3 to 4 non-AAs; group 2A, 3 to 4 adenomas with >=1 AA; group 3, >=5 non-AAs; and group 3A, >=5 adenomas with >=1 AA. The risk of advanced CRN at 3 years was compared among the 6 groups. RESULTS: Group 3A showed a higher risk of advanced CRN (9.6%) than group 3 (4.5%; P = .03) and group 1A (4.6%; P < .001). The risk of advanced CRN in group 3 (4.5%) showed no difference compared with group 1A (4.6%; P = .91) or group 2A (6.8%; P = .25). There was no difference between group 1 and group 2 in the risk of advanced CRN (1.7% vs 2.2%; P = .22). More than 1 AA at index colonoscopy was an independent risk factor for advanced CRN. CONCLUSION: More-intensive surveillance than the 3-year interval for patients with >=5 adenomas with >=1 AA and less-intensive surveillance than the 3-year and 1-year intervals for those with 3 to 4 non-AAs and >=5 non-AAs, respectively, might be suggested. PMID- 28986267 TI - Neural correlates of individuation and categorization of other-species faces in infancy. AB - The goal of this study was to investigate 9-month-old infants' ability to individuate and categorize other-species faces at the subordinate level. We were also interested in examining the effects of initial exposure conditions on infant categorization and individuation processes. Infants were either familiarized with a single monkey face in an individuation procedure or familiarized with multiple exemplars of monkey faces from the same species in a categorization procedure. Event-related potentials were recorded while the infants were presented: familiar faces, novel faces from the familiar species, or novel faces from a novel species. The categorization group categorized monkey faces by species at the subordinate level, whereas the individuation group did not discriminate monkey faces at the individual or subordinate level. These findings indicate initial exposure to multiple exemplars facilitates infant processing of other-species faces, and infants are efficient at subordinate-level categorization at 9 months of age. PMID- 28986266 TI - Pit pattern analysis with high-definition chromoendoscopy and narrow-band imaging for optical diagnosis of dysplasia in patients with ulcerative colitis. AB - BACKGROUND AND AIMS: Patients with longstanding ulcerative colitis (UC) are at increased risk of developing colorectal neoplasia. Chromoendoscopy (CE) increases detection of lesions, and Kudo pit pattern classification I and II have been suggested to be predictive of benign polyps in UC. Little is known on the use of this classification in nonmagnified high-definition (HD) (virtual) CE and narrow band Imaging (NBI) or on the interobserver agreement. The aim of this pilot study was to assess the diagnostic accuracy and the interobserver agreement of the Kudo pit pattern classification in UC patients undergoing surveillance with methylene blue CE or NBI in a multicenter study. METHODS: Fifty images of lesions identified in 27 UC patients (13 neoplastic) either with classical CE (methylene blue .1%; n = 24) or NBI (n = 26) were selected by an independent investigator. Images were selected from a randomized controlled trial to compare CE and NBI. All nonmagnified images were obtained with a processor and mounted in a PowerPoint file in a standardized way (same size; black background). Ten endoscopists with extensive experience in NBI/CE were asked to assess the lesions for the predominant Kudo pit pattern (I, II, IIIL, IIIS, IV, and V) to indicate if they believed the lesion was neoplastic and how confident they were about the diagnosis. Histology was used as the criterion standard. RESULTS: Median sensitivity, specificity, negative predictive value, and positive predictive value for diagnosing neoplasia based on the presence of pit pattern other than I or II was 77%, 68%, 88%, and 46%, respectively. Diagnostic accuracy was significantly higher when a diagnosis was made with a high level of confidence (77% vs 21%, P < .001). The overall interobserver agreement for any pit pattern was only fair (kappa = .282), with CE being significantly better than NBI (.322 vs .224, P < .001). From a clinical viewpoint the difference between neoplastic and non-neoplastic lesions is important. The agreement for differentiation between non-neoplastic patterns (I, II) and neoplastic patterns (IIIL, IIIS, IV, or V) was moderate (kappa = .587) and even significantly better for NBI in comparison with CE (kappa = .653 vs .495, P < .001). CONCLUSIONS: Differentiation between non-neoplastic and neoplastic pit patterns in UC lesions shows a moderate to substantial agreement among expert endoscopists. The agreement for differentiating neoplastic from non-neoplastic lesions is significantly better for NBI in comparison with HD CE. The assessment of pit pattern I or II with nonmagnified HD CE or NBI has a high negative predictive value to rule out neoplasia. (Clinical trial registration number: NCT01882205.). PMID- 28986268 TI - The N170 ERP component differs in laterality, distribution, and association with continuous reading measures for deaf and hearing readers. AB - The temporo-occipitally distributed N170 ERP component is hypothesized to reflect print-tuning in skilled readers. This study investigated whether skilled deaf and hearing readers (matched on reading ability, but not phonological awareness) exhibit similar N170 patterns, given their distinct experiences learning to read. Thirty-two deaf and 32 hearing adults viewed words and symbol strings in a familiarity judgment task. In the N170 epoch (120-240ms) hearing readers produced greater negativity for words than symbols at left hemisphere (LH) temporo parietal and occipital sites, while deaf readers only showed this asymmetry at occipital sites. Linear mixed effects regression was used to examine the influence of continuous measures of reading, spelling, and phonological skills on the N170 (120-240ms). For deaf readers, better reading ability was associated with a larger N170 over the right hemisphere (RH), but for hearing readers better reading ability was associated with a smaller RH N170. Better spelling ability was related to larger occipital N170s in deaf readers, but this relationship was weak in hearing readers. Better phonological awareness was associated with smaller N170s in the LH for hearing readers, but this association was weaker and in the RH for deaf readers. The results support the phonological mapping hypothesis for a left-lateralized temporo-parietal N170 in hearing readers and indicate that skilled reading is characterized by distinct patterns of neural tuning to print in deaf and hearing adults. PMID- 28986270 TI - Integrated physiological and proteomic analysis reveals underlying response and defense mechanisms of Brachypodium distachyon seedling leaves under osmotic stress, cadmium and their combined stresses. AB - : Drought stress, a major abiotic stress, commonly occurs in metal-contaminated environments and affects crop growth and yield. In this study, we performed the first integrated phenotypic, physiological, and proteomic analysis of Brachypodium distachyon L. seedling leaves under polyethylene glycol (PEG) mock osmotic stress, cadmium (Cd2+), and their combined stresses. Combined osmotic and Cd2+ stress had more significant effects than each individual stress on seedling growth, and the physiological traits and ultrastructures of leaves. Totally 117 differentially accumulated protein (DAP) spots detected by two-dimensional difference gel electrophoresis (2D-DIGE) were identified, and representing 89 unique proteins under individual and combined stresses. These DAPs were involved in photosynthesis/respiration (34%), energy and carbon metabolism (21%), stress/defense/detoxification (13%), protein folding and degradation (12%), and amino acid metabolism (7%). Principal component analysis (PCA) revealed that DAPs from the Cd2+ and combined stresses grouped much closer than those from osmotic stress, indicating Cd2+ and combined stresses resulted in more changes to the leaf proteome than osmotic stress alone. Protein-protein interaction analyses showed that a 14-3-3 centered sub-network could play important roles in responses to abiotic stresses. An overview pathway of proteome metabolic changes in Bd21 seedling leaves under combined stresses is proposed, representing a synergistic responsive network and underlying response and defense mechanisms. SIGNIFICANCE: Drought stress is one of the major abiotic stresses, which commonly occurs in metal-contaminated environments, and affects crop growth and yield performance. We performed the first integrated phenotypic, physiological and proteomic analysis of Brachypodium distachyon L. seedling leaves under drought (PEG), cadmium (Cd2+) and their combined stresses. PMID- 28986269 TI - Quantitative proteomic analysis reveals that chemotaxis is involved in chlortetracycline resistance of Aeromonas hydrophila. AB - : In recent years, Aeromonas hydrophila, which has been classified as a food borne pathogen, has presented with increased levels of antibiotic resistance, with the mechanisms of this resistance being poorly understood. In this study, iTRAQ coupled mass spectrometry was employed to compare differentially expressed proteins in chlortetracycline (CTC) resistant A. hydrophila relative to a control strain. Result showed that a total of 234 differential proteins including 151 down-regulated and 83 up-regulated were identified in chlortetracycline resistance strain. Bioinformatics analysis showed that chemotaxis related proteins, such as CheA-2, CheR-3, CheW-2, EnvZ, PolA, FliS and FliG were down regulated in addition to previously reported tricarboxylic acid cycle (TCA) related proteins also being down-regulated. A subset of identified differentially expressed proteins was then further validated via Western blotting. Exogenous metabolite combined with CTC further enhanced the bacterial susceptibilities to CTC in A. hydrophila. Furthermore, a bacterial survival capability assay showed that several chemotaxis related mutants, such as DeltacheR-3 and DeltaAHA_0305, may affect the antimicrobial susceptibility of A. hydrophila. Overall, these findings contribute to a further understanding of the mechanism of CTC resistance in A. hydrophila and may contribute to the development of more effective future treatments. BIOLOGICAL SIGNIFICANCE: A. hydrophila is a well-known fish pathogenic bacterium and has presented with increasing levels of antibiotic resistance, with the mechanisms of this resistance being poorly understood. Our current study compared the differentially expression proteins between chlortetracycline (CTC) resistant and control stains via an iTARQ-based quantitative proteomics method. Chemotaxis related proteins were down-regulated in CTC resistant strain but exogenous metabolite addition increased bacterial susceptibility in A.hydrophila. Significantly, chemotaxis related genes depletion affected antimicrobial susceptibilities of A.hydrophila indicating the role of chemotaxis process in antibiotics resistance. PMID- 28986271 TI - The Subclinical Cardiomyopathy of Friedreich's Ataxia in a Pediatric Population. AB - BACKGROUND: Identification of a subclinical cardiomyopathy in pediatric patients with Friedreich's ataxia (FA) has not been well-described. METHODS: We performed echocardiography (Echo), cardiac magnetic resonance imaging (cMRI), and neurologic assessment in a cross-sectional analysis of 48 genetically confirmed FA subjects aged 9-17 years with moderate neurologic impairment but without a cardiovascular history. Echo- and cMRI-determined left ventricular mass were indexed (LVMI) to height in grams/m2.7. LV remodeling was categorized as concentric remodeling (CR), concentric hypertrophy (CH), or eccentric hypertrophy based upon Echo- determined relative LV wall thickness. RESULTS: Echo LVMI exceeded age-based normal values in 85% of subjects, and cMRI-determined LVMI correlated with depression of both diastolic and systolic tissue Doppler velocity (E': r = -0.65, P < .001, S': r = -0.46, P < .001) as well as increased early diastolic Doppler flow velocity/tissue velocity ratio (r= 0.55, P < .001), a marker of elevated LV filling pressure. Similar associations were found with echo determined LV mass. Evidence of depressed LV relaxation and increased LV stiffness were observed in 88% and 71%, of subjects, respectively, despite a normal LV ejection fraction in almost all cases (mean = 60% + 7%). CR and CH were present in 40% and 44% of the study group, respectively, although significant depressions of E' and S' were observed only in subjects with CH (P < .005). CONCLUSIONS: A subclinical hypertrophic cardiomyopathy is common in pediatric FA patients and CH is associated with both diastolic and systolic dysfunction. PMID- 28986272 TI - The Next Blockbuster Drug? PMID- 28986274 TI - Toward a Model of Human Information Processing for Decision-Making and Skill Acquisition in Laparoscopic Colorectal Surgery. AB - OBJECTIVE: To create a human information-processing model for laparoscopic surgery based on already established literature and primary research to enhance laparoscopic surgical education in this context. DESIGN: We reviewed the literature for information-processing models most relevant to laparoscopic surgery. Our review highlighted the necessity for a model that accounts for dynamic environments, perception, allocation of attention resources between the actions of both hands of an operator, and skill acquisition and retention. The results of the literature review were augmented through intraoperative observations of 7 colorectal surgical procedures, supported by laparoscopic video analysis of 12 colorectal procedures. RESULTS: The Wickens human information processing model was selected as the most relevant theoretical model to which we make adaptions for this specific application. We expanded the perception subsystem of the model to involve all aspects of perception during laparoscopic surgery. We extended the decision-making system to include dynamic decision making to account for case/patient-specific and surgeon-specific deviations. The response subsystem now includes dual-task performance and nontechnical skills, such as intraoperative communication. The memory subsystem is expanded to include skill acquisition and retention. CONCLUSIONS: Surgical decision-making during laparoscopic surgery is the result of a highly complex series of processes influenced not only by the operator's knowledge, but also patient anatomy and interaction with the surgical team. Newer developments in simulation-based education must focus on the theoretically supported elements and events that underpin skill acquisition and affect the cognitive abilities of novice surgeons. The proposed human information-processing model builds on established literature regarding information processing, accounting for a dynamic environment of laparoscopic surgery. This revised model may be used as a foundation for a model describing robotic surgery. PMID- 28986273 TI - ITE Suppresses Angiogenic Responses in Human Artery and Vein Endothelial Cells: Differential Roles of AhR. AB - Aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor is involved in regulation of many essential biological processes including vascular development and angiogenesis. 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) is an AhR ligand, which regulates immune responses and cancer cell growth. However, the roles of the ITE/AhR pathway in mediating placental angiogenesis remains elusive. Here, we determined if ITE affected placental angiogenic responses via AhR in human umbilical vein (HUVECs) and artery endothelial (HUAECs) cells in vitro. We observed that ITE dose- and time dependently inhibited proliferation and viability of HUAECs and HUVECs, whereas it inhibited migration of HUAECs, but not HUVECs. While AhR siRNA significantly suppressed AhR protein expression in HUVECs and HUAECs, it attenuated the ITE inhibited angiogenic responses of HUAECs, but not HUVECs. Collectively, ITE suppressed angiogenic responses of HUAECs and HUVECs, dependent and independent of AhR, respectively. These data suggest that ITE may regulate placental angiogenesis. PMID- 28986275 TI - Quantification of Resident Work in Colorectal Surgery. AB - OBJECTIVE: To examine resident intraoperative participation, perceived autonomy, and communication patterns between residents and attending surgeons using a novel survey tool. DESIGN: This was a prospective multi-institutional study. Operative residents completed the survey tool immediately after each colorectal resection performed during the study period. Resident intraoperative participation was quantified including degree of involvement in the technical aspects of the case, self-perception of autonomy, and communication strategies between the resident and attending. SETTING: This study was conducted at 7 general surgery residency programs: 5 academic medical centers, and 2 independent training programs. PARTICIPANTS: Residents and fellows rotating on a colorectal surgery service or general surgery service. RESULTS: Sixty-three residents participated in this study with 417 surveys completed (range 19-79 per institution) representing a 95.4% response rate across all sites. Respondents ranged from clinical year 1 (CY1) to fellows. CY3s (35.7%) and CY5s (34.7%) were most heavily represented. Residents completed >=50% of the skin closure in 88.7% of cases, >=50% of the fascial closure in 87.1%, and t >= 50% of the anastomosis in 78.4% of the cases. Increasing resident participation was associated with advancing resident CY across all technical aspects of the case. This trend remained significant when controlling for site (p < 0.001). Resident self-perception of autonomy revealed learners of all stages: Observer (11.5%, n = 48), Assistant (53.7%, n = 224), Surgeon (33.8%, n = 141), and Teacher (0.96%, n = 4). Level of perceived autonomy increased with resident CY when controlling for site (p < 0.001). Residents who discussed the case before the day of surgery were twice as likely to rate themselves as Surgeon or Teacher (OR = 2.01) when controlling for CY (p = 0.011). CONCLUSIONS: Brief surveys can easily capture resident work in the operating room. Resident intraoperative involvement and perceived autonomy are associated with CY. Early communication with the attending is significantly associated with increased perception of autonomy regardless of CY. PMID- 28986276 TI - Expression and localization of relaxin family peptide receptor 4 in human spermatozoa and impact of insulin-like peptide 5 on sperm functions. AB - Insulin-like peptide 5 (INSL5) is a member of the insulin superfamily peptide that interacts with the relaxin family peptide receptor 4 (RXFP4). Numerous recent studies have focused on the functional effects of INSL5 on fat and glucose metabolism. Although there is no evidence that the human sperm may be a candidate target of INSL5, it has been detected in mice testis and sperm. Therefore, the present study sought to analyze the localization and expression of RXFP4 on human sperm and determine the efficiency of INSL5 in human sperm. Normal semen samples were incubated in different doses and exposure time periods of INSL5. We analyzed sperm motility by computer-assisted sperm analysis (CASA) and ROS levels by flow cytometry using the MitoSOXTM Red probe. Localization and expression of RXFP4 were assayed by immunofluorescence and RT-PCR, respectively. The results confirmed the presence of RXFP4 in human spermatozoa, which localized in the neck and midpiece of sperm. Nested PCR showed the expression of RXFP4 in human sperm. INSL5 could attenuate generation of mitochondrial ROS at the 1, 10, 30, and 100nmol/L doses. This result was particularly noted in the 30nmol/L treated samples after 4h incubation. Total motility of sperm was significantly preserved in the 100nmol/L after 2h and in 30nmol/L after 4h incubation period. This study, for the first time, clarified the expression and localization of RXFP4 on human sperm and revealed the role of INSL5 in sperm motility and mitochondrial ROS generation in a dose-dependent manner. PMID- 28986277 TI - Upregulation of peripheral CXC and CC chemokine receptor expression on CD4+ T cells is associated with immune dysregulation in children with autism. AB - Autism spectrum disorders (ASD) are characterized by disturbances in social interactions and communication, restricted repetitive interests, and stereotyped behavior. Cumulative evidence recommends that there are immune alterations in ASD. Chemokine receptors are known to play an important role in the central nervous system (CNS) and in many neuro inflammatory disorders. The main objective of this study was to explore the role of CXC and CC chemokine receptors signaling in children with autism. We examined chemokine receptor production of CXCR2, CXCR3, CXCR5, and CXCR7 in all peripheral blood mononuclear cells (PBMCs) and in CD4+ T cells of typically developing control children (TD) and autistic children (AU). We also examined chemokine receptor production of CCR3, CCR5, CCR7, and CCR9 in all PBMCs and in CD4+ T cells of AU and TD samples using flow cytometric analysis. In addition, we measured mRNA expression levels of CXC and CC chemokine receptors using quantitative RT-PCR analysis. Our results showed the increased production of CXCR2+, CXCR3+, CXCR5+, and CXCR7+ and CCR3+, CCR5+, CCR7+, and CCR9+ in all PBMCs and in CD4+ T cells of children with AU as compared to TD controls. Our results show that chemokine receptor signaling components might provide unique therapeutic targets for children with AU and other neurological disorders. PMID- 28986278 TI - Synaptopathology in autism spectrum disorders: Complex effects of synaptic genes on neural circuits. PMID- 28986279 TI - Progressive modulation of accumbal neurotransmission and anxiety-like behavior following protracted nicotine withdrawal. AB - Due to the highly addictive properties of nicotine, a low percentage of users successfully maintain cessation for longer periods of time. This might be linked to neuroadaptations elicited by the drug, and understanding progressive changes in neuronal function might provide critical insight into nicotine addiction. We have previously shown that neurotransmission in the nucleus accumbens (nAc), a key brain region with respect to drug reinforcement and relapse, is suppressed for as long as seven months after a brief period of nicotine treatment. Studies were therefore performed to define the temporal properties of these effects, and to assess behavioral correlates to altered neurotransmission. Ex vivo electrophysiology revealed progressive depression of synaptic efficacy in the nAc of rats previously receiving nicotine. In addition, following three months of nicotine withdrawal, the responses to GABAA receptor modulating drugs were blunted together with downregulation of several GABAA receptor subunits. In correlation to reduced accumbal neurotransmission, a reduced anxiety-like behavior; assessed in the elevated plus-maze and marble burying tests, were identified in animals pre-treated with nicotine. Lastly, to test the causal relationship between suppressed excitability in the nAc and reduced anxiety-like behavior, rats received local administration of diazepam in the nAc while monitoring behavioral effects on the elevated plus-maze. These results show that nicotine produces long-lasting changes in the GABAergic system, which are observed first after extended withdrawal. Our data also suggest that nicotine produces a progressive suppression of accumbal excitability, which could result in behavioral alterations that may have implications for further drug intake. PMID- 28986280 TI - Recombinant tissue plasminogen activator induces long-term anxiety-like behaviors via the ERK1/2-GAD1-GABA cascade in the hippocampus of a rat model. AB - OBJECTIVES: Recombinant tissue plasminogen activator (rtPA) is widely used for patients with thromboembolic disease, and increasing evidence indicates that it can directly induce neurotoxicity independent of its thrombolysis property. Here, we aimed to confirm the long-term effect of rtPA on animal's behavior, and investigate the underlying pathogenesis. METHODS AND RESULTS: Male Sprague-Dawley rats randomly received a dose of rtPA (10 mg/kg) or sterile saline. Three months later, the animals receiving rtPA displayed anxiety-like behaviors in the open field and novelty-suppressed feeding tests. To investigate the possible pathogenesis, gas chromatography-mass spectrometry-based metabolomics analysis was performed, with 18 differential metabolites identified in the hippocampus 24 h after the treatments. Based upon these differential metabolites, a metabolite protein integrated network was generated, which indicated that ERK1/2-glutamic acid decarboxylase (GAD) 1-gamma aminobutyric acid (GABA) cascade may be related to long-term anxiety-like behaviors. The GABA levels in hippocampus were decreased 24 h post-treatment and three months later, confirmed by a high performance liquid chromatography method. We also examined the expression of GAD1 and GAD2 using western blotting or immunohistochemical staining. Levels of GAD1 were persistently decreased after treatment, while GAD2 levels, GAD1 immunoreactive, and GAD2-immunoreactive neurons showed no significant differences. The underlying pathogenesis also involved activation of ERK1/2, confirmed by increased phospho-ERK1/2 24 h post-treatment. CONCLUSIONS: RtPA can induce long-term anxiety-like behaviors after a clinical injected dose. The underlying pathogenesis involves the ERK1/2-GAD1-GABA cascade in the hippocampus. This pharmacological side effect of rtPA may further exacerbate post-stroke anxiety disorder for stroke patients. PMID- 28986281 TI - Interference of norepinephrine transporter trafficking motif attenuates amphetamine-induced locomotor hyperactivity and conditioned place preference. AB - Amphetamine (AMPH)-mediated norepinephrine transporter (NET) downregulation requires NET-T258/S259 trafficking motif. The present study utilizes cell permeable NET-T258/S259 motif interfering peptide, which blocks AMPH-induced NET downregulation, to explore the role of this form of NET regulation in AMPH mediated behaviors. In rats receiving intra-accumbal microinjections of TAT conjugated peptides encompassing NET-T258/S259 motif, acute systemic AMPH failed to inhibit NE transport in the TAT-NET-T258/S259 wild-type (WT) peptide injected hemisphere but not in the vehicle or scrambled peptide injected hemisphere. Acute AMPH-induced hyperactivity was significantly reduced in rats receiving intra accumbal TAT-NET-T258/S259 WT peptide compared to those receiving intra-accumbal vehicle or TAT-NET-T258A/S259A mutant peptide or corresponding TAT-conjugated scrambled peptide. Basal locomotor activity was not altered by peptide infusions alone. Similarly AMPH-induced locomotor sensitization was significantly reduced in rats receiving intra-accumbal TAT-NET-T258/S259 WT peptide prior to AMPH challenge and not in rats receiving the mutant or scrambled peptide. In conditioned place preference (CPP) paradigm, a single bilateral intra-accumbal microinjection of TAT-NET-T258/S259 WT peptide prior to CPP testing significantly reduced AMPH-induced CPP expression. Likewise, a single bilateral intra-accumbal microinjection of TAT-NET-T258/S259 WT peptide prior to drug-challenge significantly attenuated AMPH-primed CPP reinstatement. On the other hand, bilateral intra-accumbal microinjection of scrambled peptide did not affect AMPH induced CPP expression or reinstatement. These data demonstrate a role for T258/S259-dependent NET regulation in AMPH-induced hyperactivity and sensitization as well as AMPH-induced CPP expression and reinstatement. PMID- 28986282 TI - Exendin-4 attenuates neuronal death via GLP-1R/PI3K/Akt pathway in early brain injury after subarachnoid hemorrhage in rats. AB - Neuronal apoptosis is considered to be a crucial therapeutic target against early brain injury (EBI) after subarachnoid hemorrhage (SAH). Emerging evidence indicates that Exendin-4 (Ex-4), a glucagon-like peptide 1 receptor (GLP-1R) agonist, plays a neuroprotective role in cerebrovascular disease. This study was conducted in order to verify the neuroprotective role of EX-4 in EBI after SAH in rats. The endovascular perforation model of SAH was performed in Sprague-Dawley rats (n = 153). Ex-4 was intraperitoneally injected 1 h after SAH induction in the rats (SAH + Ex-4). To elucidate the underlying molecular mechanism, small interfering ribonucleic acid (siRNA) for GLP-1R and a specific inhibitor of PI3K, LY294002, were injected intracerebroventricularly into SAH + Ex-4 rats before induction of SAH (n = 6 per group). SAH grading evaluation, immunohistochemistry, Western blots, neurobehavioral assessment, and Fluoro-Jade C (FJC) staining experiments were performed. Expression of GLP-1R was significantly increased and mainly expressed in neurons at 24 h after SAH induction. Administration of Ex-4 significantly improved both short- and long-term neurobehavior in SAH + Ex-4 group compared to SAH + Vehicle group after SAH. Ex-4 treatment significantly increased the expression of GLP-1R, PI3K, p-Akt, Bcl-xl, and Bcl-2, while at the same time was found to decrease expression of Bax in the brain. Effects of Ex-4 were reversed by the intervention of GLP-1R siRNA and LY294002 in SAH + Ex-4+GLP 1R siRNA and SAH + Ex-4+LY294002 groups, respectively. In conclusion, the neuroprotective effect of Ex-4 in EBI after SAH was mediated by attenuation of neuronal apoptosis via GLP-1R/PI3K/Akt signaling pathway, therefore EX-4 should be further investigated as a potential therapeutic agent in stroke patients. PMID- 28986283 TI - Effects of high-fat diet and age on the blood lipidome and circulating endocannabinoids of female C57BL/6 mice. AB - Alterations in lipid metabolism play a significant role in the pathogenesis of obesity-associated disorders, and dysregulation of the lipidome across multiple diseases has prompted research to identify novel lipids indicative of disease progression. To address the significant gap in knowledge regarding the effect of age and diet on the blood lipidome, we used shotgun lipidomics with electrospray ionization-mass spectrometry (ESI-MS). We analyzed blood lipid profiles of female C57BL/6 mice following high-fat diet (HFD) and low-fat diet (LFD) consumption for short (6weeks), long (22weeks), and prolonged (36weeks) periods. We examined endocannabinoid levels, plasma esterase activity, liver homeostasis, and indices of glucose tolerance and insulin sensitivity to compare lipid alterations with metabolic dysregulation. Multivariate analysis indicated differences in dietary blood lipid profiles with the most notable differences after 6weeks along with robust alterations due to age. HFD altered phospholipids, fatty acyls, and glycerolipids. Endocannabinoid levels were affected in an age-dependent manner, while HFD increased plasma esterase activity at all time points, with the most pronounced effect at 6weeks. HFD-consumption also altered liver mRNA levels of PPARalpha, PPARgamma, and CD36. These findings indicate an interaction between dietary fat consumption and aging with widespread effects on the lipidome, which may provide a basis for identification of female-specific obesity- and age related lipid biomarkers. PMID- 28986284 TI - Electrophysiological indicators of inhibitory control deficits in depression. AB - Ample evidence from behavioral and brain imaging studies suggests that inhibitory control is impaired in depression, though the precise nature of this impairment is unclear. The purpose of the present study was to examine potential deficits in three aspects of inhibitory control - conflict monitoring, conflict resolution, and overt behavioral inhibition - in the context of depressive symptoms. Depressed (n=15) and non-depressed (n=15) participants completed a stop-signal reaction time (SSRT) task while electroencephalography (EEG) data were recorded. EEG results indicate that depression impacts only the conflict resolution phase of inhibitory control, with higher levels of depressive and reflective pondering symptoms associated with poorer conflict resolution. Findings have clear implications for treatments of depression, many of which do not currently target the inhibitory control deficits present in this disorder. PMID- 28986285 TI - Gene expression signatures after ethanol exposure in differentiating embryoid bodies. AB - During the differentiation process, various epigenetic factors regulate the precise expression of important genes and control cellular fate. During this stage, the differentiating cells become vulnerable to external stimuli. Here, we used an early neural differentiation model to observe ethanol-mediated transcriptional alterations. Our objective was to identify important molecular regulators of ethanol-related alterations in the genome during differentiation. A transcriptomic analysis was performed to profile the mRNA expression in differentiating embryoid bodies with or without ethanol treatment. In total, 147 differentially expressed genes were identified in response to 50mM ethanol. Of these differentially expressed genes, 78 genes were up-regulated and 69 genes were down-regulated. Our analysis revealed a strong association among the transcript signatures of the important modulators which were involved in protein modification, protein synthesis and gene expression. Additionally, ethanol mediated activation of DNA transcription was observed. We also profiled ethanol responsive transcription factors (TFs), upstream transcriptional regulators and TF-binding motifs in the differentiating embryoid bodies. In this study, we established a platform that we hope will help other researchers determine the ethanol-mediated changes that occur during cellular differentiation. PMID- 28986286 TI - Differential responses of lineages-committed hematopoietic progenitors and altered expression of self-renewal and differentiation-related genes in 1,4 benzoquinone (1,4-BQ) exposure. AB - Despite of reports on hematotoxic and leukemogenic evidences related to benzene exposure, the mechanism of benzene toxicity affecting the hematopoietic stem and progenitor cells (HSPCs) fate remains unclear. This study aims to elucidate the benzene's effect on the lineages-committed progenitors and genes-regulating self renewal and differentiation of HSPCs. Isolated mouse bone marrow (BM) cells were exposed to the benzene metabolite, 1,4-benzoquinone (1,4-BQ) at 1.25, 2.5, and 5MUM for 24h. The clonogenic potency of erythroid, myeloid, and Pre-B lymphoid progenitors was evaluated through colony-forming-cell assay. Quantitative real time-PCR was used to analyze the self-renewal (Bmi-1, HoxB4, and Wnt3) and differentiation (GATA1, GATA2, and GATA3)-related genes' expression levels. 1,4 BQ exposure significantly lowered the clonogenicity of the myeloid progenitor at 1.25 and 2.5MUM (p<0.05), but affected neither the erythroid nor Pre-B lymphoid progenitors. Furthermore, significant upregulation of HoxB4 expression level was observed at all concentrations. GATA3 and Bmi-1 expressions were also significant upregulated at 2.5 and 5MUM 1,4-BQ, respectively. In conclusion, 1,4-BQ could modulate the fate of HSPCs by altering the self-renewal and differentiation related genes. The definite role of lineages specificity and responsive genes in governing the hematotoxicity and leukemogenicity of 1,4-BQ should be further investigated. PMID- 28986287 TI - Deciphering the molecular mechanism underlying anticancer activity of coumestrol in triple-negative breast cancer cells. AB - Triple-negative breast cancer (TNBC) represents the highly aggressive subgroup of breast cancers with poor prognosis due to absence of estrogen receptor (ER). Therefore, alternative targeted therapies are required against ER-negative breast cancers. Coumestrol, a phytoestrogen inhibits cell growth of ER-negative breast cancer MDA-MB-231 cells; the exact mechanism has not yet been reported. Unlike normal cells, cancer cells contain elevated copper which play an integral role in angiogenesis. The current focus of the work was to identify any possible role of copper in coumestrol cytotoxic action against breast cancer MDA-MB-231 cells. Results demonstrated that coumestrol inhibited cell viability, induced ROS generation, DNA damage, G1/S cell cycle arrest, up-regulation of Bax and apoptosis induction via caspase-dependent mitochondrial mediated pathway in MDA MB-231 cells. Further, addition of copper chelator, neocuproine and ROS scavenger, N-acetyl cysteine were ineffective in abrogating coumestrol-mediated apoptosis. This suggests non-involvement of copper and ROS in coumestrol-induced apoptosis. To account for coumestrol-mediated up-regulation of Bax and apoptosis induction, direct binding potential between coumestrol and Bax/Bcl-2 was studied using in silico molecular docking studies. We propose that coumestrol directly enters cells and combines with Bax/Bcl-2 to alter their structures, thereby causing Bax binding to the outer mitochondrial membrane and Bcl-2 release from the mitochondria to initiate apoptosis. Thus, non-copper targeted ROS independent DNA damage is the central mechanism of coumestrol in ER-negative MDA-MB-231 cells. These findings will be useful in better understanding of anticancer mechanisms of coumestrol and establishing it as a lead molecule for TNBC treatment. PMID- 28986288 TI - Manganese exposure: Linking down-regulation of miRNA-7 and miRNA-433 with alpha synuclein overexpression and risk of idiopathic Parkinson's disease. AB - Manganese is an essential trace element however elevated environmental and occupational exposure to this element has been correlated with neurotoxicity symptoms clinically identical to idiopathic Parkinson's disease. In the present study we chronically exposed human neuroblastoma SH-SY5Y cells to manganese (100MUM) and carried out expression profiling of miRNAs known to modulate neuronal differentiation and neurodegeneration. The miRNA PCR array results reveal alterations in expression levels of miRNAs, which have previously been associated with the regulation of synaptic transmission and apoptosis. The expressions of miR-7 and miR-433 significantly reduced upon manganese exposure. By in silico homology analysis we identified SNCA and FGF-20as targets of miR-7 and miR-433. We demonstrate an inverse correlation in expression levels where reduction in these two miRNAs causes increases in SNCA and FGF-20. Transient transfection of SH-SY5Y cells with miR-7 and miR-433 mimics resulted in down regulation of SNCA and FGF-20 mRNA levels. Our study is the first to uncover the potential link between manganese exposure, altered miRNA expression and parkinsonism: manganese exposure causes overexpression of SNCA and FGF-20 by diminishing miR-7 and miR-433 levels. These miRNAs may be considered critical for protection from manganese induced neurotoxic mechanism and hence as potential therapeutic targets. PMID- 28986289 TI - Eukaryotic translation initiation factor 2 subunit alpha (eIF2alpha) inhibitor salubrinal attenuates paraquat-induced human lung epithelial-like A549 cell apoptosis by regulating the PERK-eIF2alpha signaling pathway. AB - Paraquat (PQ), as one of the most widely used herbicides in the world, can cause severe lung damage in humans and animals. This study investigated the underlying molecular mechanism of PQ-induced lung cell damage and the protective role of salubrinal. Human lung epithelial-like A549 cells were treated with PQ for 24h and were pre-incubated with salubrinal for 2h, followed by 500MUM of PQ treatment. Silencing eIF2alpha gene of the A549 cells with siRNA interference method was conducted. Cell morphology, cell viability, apoptosis and caspase-3 activity were assessed by different assays accordingly thereafter. The expression of PERK, p-PERK, ATF6, c-ATF6, IRE1alpha, p-IRE1alpha, CHOP, GRP78, p-eIF2alpha and beta-actin was assayed by western blot. The data showed that PQ significantly reduced A549 cell viability, changed cell morphology, induced cell apoptosis and significantly upregulated the levels of GRP78, CHOP, p-PERK, c-ATF6 and p IRE1alpha. However, 30MUM salubrinal could attenuate the effects of PQ on damages to A549 cells through upregulating p-eIF2alpha. In contrast, knocking down eIF2alpha gene inhabited the effects of salubrinal. These results suggest that PQ induced A549 cell apoptosis involved endoplasmic reticulum (ER) stress, specially the PERK-eIF2alpha pathway. Salubrinal attenuated A549 cells from PQ-induced damages through regulation of the PERK-eIF2alpha signaling. PMID- 28986290 TI - Assessment of hepatic metabolism-dependent nephrotoxicity on an organs-on-a-chip microdevice. AB - Drug-induced nephrotoxicity is one of the most frequent adverse events in pharmacotherapy. It has resulted in numerous clinical trial failures and high drug development costs. The predictive capabilities of existing in vitro models are limited by their inability to recapitulate the complex process of drug metabolism at the multi-organ level in vivo. We present a novel integrated liver kidney chip that allows the evaluation of drug-induced nephrotoxicity following liver metabolism in vitro. The liver-kidney chip consists of two polydimethylsiloxane layers with compartmentalized micro-channels separated by a porous membrane. Hepatic and renal cells were co-cultured in separate micro chambers on a single chip. Ifosfamide and verapamil were used as model drugs, and their metabolites produced by hepatic metabolism were identified using mass spectrometry, respectively. The metabolites triggered significantly distinct nephrotoxic effects as assessed by cell viability, lactate dehydrogenase leakage and permeability of renal cells. This in vitro liver-kidney model facilitates the characterization of drug metabolism in the liver as well as the assessment of subsequent nephrotoxicity in a single assay. Obviously, this multi-organ platform is simple and scalable, and maybe widely applicable to the evaluation of drug metabolism and safety during the early phases of drug development. PMID- 28986291 TI - Molecular detection of feline calicivirus in clinical samples: A study comparing its detection by RT-qPCR directly from swabs and after virus isolation. AB - Feline caliciviruses (FCVs) are non-enveloped RNA viruses that exhibit high genetic variation. Two reverse transcription quantitative polymerase chain reaction (RT-qPCR) FCV assays (S1 and S2) were evaluated using samples from 300 field cats. The direct detection of FCV in swabs and after propagation in cell culture, as well as the influence of storage conditions, was assessed. FCV-RNA detectability on dry swabs was similar after storage at either 4 degrees C or -20 degrees C, but viral burdens were maintained for a longer time period when viral transport medium was used. A total of 97 (32%) samples was considered FCV PCR positive. Of these, 81% and 77% tested positive directly from swabs using S1 and S2, respectively; 84% and 81% tested positive after enrichment in cell culture, respectively. Combined detection by RT-PCR directly from swabs and after VI was most sensitive (up to 96%). Neither of the methods alone were able to detect all FCV-positive samples. In conclusion, clinical samples should be collected in viral transport medium, stored at <=4 degrees C and processed as soon as possible. The combination of cell culture with RT-qPCR or detection directly from swabs using a combination of different RT-qPCR assays is recommended to reach a high sensitivity of FCV detection. PMID- 28986292 TI - Validation of an indirect ELISA employing a chimeric recombinant gag and env peptide for the serological diagnosis of equine infectious anemia. AB - The National Reference Center for equine infectious anemia (EIA) validated a commercial ELISA (Eradikit(r) EIAV Indirect ELISA, In3diagnostic(r), Turin, Italy) employing a chimeric recombinant gag and env peptide for the detection of EIA virus antibodies, following the guidelines of the World Organization for Animal Health. The validation parameters evaluated were: analytical sensitivity (Se) and specificity (Sp); diagnostic Se and Sp; precision, based on repeatability and reproducibility through the estimation of the standard deviation (SD) and the coefficient of variation (CV); accuracy, estimated from a multiple K and relative Sp and Se with respect to those of the agar gel immunodiffusion test (AGIDT). Positive and negative predictive values were also defined. The assay showed a high specificity and a limit of detection of 1.43 log10 major than AGIDT. Diagnostic Se was 100% and Sp was 99.3%, while SD values ranged from 1.58 to 5.01 with a CV between 2.8% and 28.8%. Multiple K was 0.98 and relative Se and Sp were respectively 99.1% and 100%. The assay proved to be robust and to possess a high sensitivity in detecting first antibodies produced at onset of infection as well as high analytic and diagnostic Se and Sp values, confirming it as a serological assay fit for purpose within EIA surveillance programs. PMID- 28986293 TI - Complete genome sequence of Acidihalobacter prosperus strain F5, an extremely acidophilic, iron- and sulfur-oxidizing halophile with potential industrial applicability in saline water bioleaching of chalcopyrite. AB - Successful process development for the bioleaching of mineral ores, particularly the refractory copper sulfide ore chalcopyrite, remains a challenge in regions where freshwater is scarce and source water contains high concentrations of chloride ion. In this study, a pure isolate of Acidihalobacter prosperus strain F5 was characterized for its ability to leach base metals from sulfide ores (pyrite, chalcopyrite and pentlandite) at increasing chloride ion concentrations. F5 successfully released base metals from ores including pyrite and pentlandite at up to 30gL-1 chloride ion and chalcopyrite up to 18gL-1 chloride ion. In order to understand the genetic mechanisms of tolerance to high acid, saline and heavy metal stress the genome of F5 was sequenced and analysed. As well as being the first strain of Ac. prosperus to be isolated from Australia it is also the first complete genome of the Ac. prosperus species to be sequenced. The F5 genome contains genes involved in the biosynthesis of compatible solutes and genes encoding monovalent cation/proton antiporters and heavy metal transporters which could explain its abilities to tolerate high salinity, acidity and heavy metal stress. Genome analysis also confirmed the presence of genes involved in copper tolerance. The study demonstrates the potential biotechnological applicability of Ac. prosperus strain F5 for saline water bioleaching of mineral ores. PMID- 28986294 TI - Use of antimicrobial photodynamic therapy in the conservative clinical management of caries lesions on a permanent tooth. PMID- 28986295 TI - Optimization and evaluation of zein nanoparticles to improve the oral delivery of glibenclamide. In vivo study using C. elegans. AB - The aim of this work was to evaluate the capability of zein nanoparticles as oral carriers for glibenclamide (GB). Nanoparticles were prepared by a desolvation procedure in the presence of lysine as stabilizer. A central composite design was used to optimize this preparative process. Under the selected conditions, nanoparticles displayed a size of about 190 nm, a surface charge of -37mV and a payload of 45ug GB/mg. Small-angle neutron scattering and X-ray diffraction techniques suggested an internal fractal-like structure, based on the repetition of spherical blocks of zein units (about 20nm) grouped to form the nanoparticles. This structure, stabilized by lysine molecules located at the surface, would determine the release of GB (molecularly trapped into the nanoparticles) by a pure diffusion mechanism. Moreover, GB-loaded nanoparticles induced a significant hypolipidemic effect with a reduction of about 15% in the fat content of C. elegans worms. In addition, did not induce any significant modification in the lifespan of worms. In summary, the employment of zein nanoparticles as delivery systems of glibenclamide may be an interesting approach to develop new oral formulations of this antidiabetic drug. PMID- 28986296 TI - Influence of PVP molecular weight on the microwave assisted in situ amorphization of indomethacin. AB - In situ amorphization is an approach that enables a phase transition of a crystalline drug to its amorphous form immediately prior to administration. In this study, three different polyvinylpyrrolidones (PVP K12, K17 and K25) were selected to investigate the influence of the molecular weight of the polymer on the degree of amorphization of the model drug indomethacin (IND) upon microwaving. Powder mixtures of crystalline IND and the respective PVP were compacted at 1:2 (w/w) IND:PVP ratios, stored at 54% RH and subsequently microwaved with a total energy input of 90 or 180kJ. After storage, all compacts had a similar moisture content (~10% (w/w)). Upon microwaving with an energy input of 180kJ, 58+/-4% of IND in IND:PVP K12 compacts was amorphized, whereas 31+/-8% of IND was amorphized by an energy input of 90kJ. The drug stayed fully crystalline in all IND:PVP K17 and IND:PVP K25 compacts. After plasticization by moisture, PVP K12 reached a Tg below ambient temperature (16+/-2 degrees C) indicating that the Tg of the plasticized polymer is a key factor for the success of in situ amorphization. DSC analysis showed that the amorphized drug was part of a ternary glass solution consisting of IND, PVP K12 and water. In dissolution tests, IND:PVP K12 compacts showed a delayed initial drug release due to a lack of compact disintegration, but reached a higher total drug release eventually. In summary, this study showed that the microwave assisted in situ amorphization was highly dependent on the Tg of the plasticized polymer. PMID- 28986297 TI - Spray-congealed solid lipid microparticles as a new tool for the controlled release of bisphosphonates from a calcium phosphate bone cement. AB - The aim of this work was to develop an innovative drug delivery system potentially useful for the local delivery of Bisphosphonates to bone tissue. We propose the use of Solid Lipid Microparticles (MPs), up to now mainly used for oral and topical drug delivery, as carrier for bisphosphonates due to the favourable biocompatibility and lower toxicity of the lipids compared with many polymers. The delivery platform consisted of a biomimetic alpha-tricalcium phosphate-gelatin cement (CPC) enriched with alendronate loaded MPs (MPs-AL) produced by the spray congealing technology. Alendronate direct addition to cement composition is limited since Alendronate is able to sequester calcium from calcium phosphates, thus preventing the setting of the cements. At variance, this approach permitted to load a relatively high amount of the drug on the CPC and allowed the controlled release of the highly water soluble alendronate. A Design of Experiment (DoE) was employed for the screening of the effects of the formulation variables related to the presence of unloaded microparticle (MPs) on the cement most important mechanical properties. Then, MPs loaded with 10% w/w of alendronate were produced using five different carriers (Stearic Acid, Stearilic Alcohol, Cutina HR, Tristearin and Precirol ATO5). All MPs-AL exhibited a spherical shape, encapsulation efficiency higher than 90% and prevalent particle size ranging from 100 to 150MUm. Solid state characterization (DSC, HSM and X-ray powder diffraction) demonstrated that encapsulation of alendronate into MPs did not alter its crystal structure. MPs-AL addition to the cement provoked a modest lengthening of the setting times and of the hardening reaction leading to the complete transformation of alpha-tricalcium phosphate into calcium-deficient hydroxyapatite, without significantly affect the cement mechanical properties. Moreover, the results of in vitro AL release study performed on cements enriched with MPs-AL showed that the system allows a controlled release of the drug over time. PMID- 28986299 TI - Reversible inactivation of the lateral hypothalamus reversed high reward choices in cost-benefit decision-making in rats. AB - The Lateral hypothalamus (LH) is an important component of the networks underlying the control of feeding and other motivated behaviors. Cost-benefit decision-making is mediated largely by the prefrontal cortex (PFC) which strongly innervates the LH. Therefore, in the current study, we conducted a series of experiments to elucidate the role of the perifornical area of the lateral hypothalamus (PeF-LH) in effort and/or delay-based decision-making. We trained different groups of rats in a delay-based and/or an effort-based form of cost benefit T-maze decision- making task in which they could either choose to pay the cost to obtain a high reward in one arm or could obtain a low reward in the other arm with no cost. During test days, the rats received local injections of either vehicle or lidocaine4% (0.5 MUl/side), in the PeF-LH. In an effort-based decision task, PeF-LH inactivation led to decrease in high reward choice. Similarly, in a delay-based decision task animals' preference changed to a low but immediately available reward. This was not caused by a spatial memory or motor deficit. PeF LH inactivation modified decision behavior. The results imply that PeF-LH is important for allowing the animal to pay a cost to acquire greater rewards. PMID- 28986298 TI - The central active site arginine in sulfite oxidizing enzymes alters kinetic properties by controlling electron transfer and redox interactions. AB - A central conserved arginine, first identified as a clinical mutation leading to sulfite oxidase deficiency, is essential for catalytic competency of sulfite oxidizing molybdoenzymes, but the molecular basis for its effects on turnover and substrate affinity have not been fully elucidated. We have used a bacterial sulfite dehydrogenase, SorT, which lacks an internal heme group, but transfers electrons to an external, electron accepting cytochrome, SorU, to investigate the molecular functions of this arginine residue (Arg78). Assay of the SorT Mo centre catalytic competency in the absence of SorU showed that substitutions in the central arginine (R78Q, R78K and R78M mutations) only moderately altered SorT catalytic properties, except for R78M which caused significant reduction in SorT activity. The substitutions also altered the Mo-centre redox potentials (MoVI/V potential lowered by ca. 60-80mV). However, all Arg78 mutations significantly impaired the ability of SorT to transfer electrons to SorU, where activities were reduced 17 to 46-fold compared to SorTWT, precluding determination of kinetic parameters. This was accompanied by the observation of conformational changes in both the introduced Gln and Lys residues in the crystal structure of the enzymes. Taking into account data collected by others on related SOE mutations we propose that the formation and maintenance of an electron transfer complex between the Mo centre and electron accepting heme groups is the main function of the central arginine, and that the reduced turnover and increases in KMsulfite are caused by the inefficient operation of the oxidative half reaction of the catalytic cycle in enzymes carrying these mutations. PMID- 28986300 TI - Echogenicity enhancement by end-fluorinated polylactide perfluorohexane nanocapsules: Towards ultrasound-activable nanosystems. AB - : Polylactide (PLA) polymers containing five distinct lengths of fluorinated (from C3F7 to C13F27) and non-fluorinated (C6H13) end-groups were successfully synthesized by ring-opening polymerization of d,l-lactide. Fluorination was expected to increase the encapsulation efficiency of perfluorohexane (PFH). 150 nm nanocapsules were obtained and 19F nuclear magnetic resonance revealed that nanocapsules formulated with fluorinated polymers increased by 2-fold the encapsulation efficiency of PFH compared with non-fluorinated derivatives, without any effect of fluorine chain length. Fluorination of the polymers did not induce any specific in vitro cytotoxicity of nanocapsules towards HUVEC and J774.A1 cell lines. The echogenicity of fluorinated-shelled nanocapsules was increased by 3-fold to 40-fold compared to non-fluorinated nanocapsules or nanoparticles devoid of a perfluorohexane core for both conventional and contrast specific ultrasound imaging modalities. In particular, an enhanced echogenicity and contrast-specific response was observed as the fluorinated chain-length increased, probably due to an increase of density and promotion of bubble nucleation. When submitted to focused ultrasound, both intact and exploded nanocapsules could be observed, also with end-group dependency, indicating that PFH was partly vaporized. These results pave the way to the design of theranostic perfluorohexane nanocapsules co-encapsulating a drug for precision delivery using focused ultrasound. STATEMENT OF SIGNIFICANCE: We have synthesized novel fluorinated polyesters and formulated them into nanocapsules of perfluorohexane as ultrasound contrast agents. This nanosystem has been thoroughly characterized by several techniques and we show that fluorination of the biodegradable polymer favors the encapsulation of perfluorohexane without producing further reduction of cell viability. Contrary to nanocapsules of perfluoroctyl bromide formulated with the fluorinated polymers [32], the presence of the fluorinated moieties leads to an increase of echogenicity that is dependent of the length of the fluorinated moiety. Morevover, the ability of nanocapsules to explode when submitted to focused ultrasound also depends on the length of the fluorinated chain. These results pave the way to theranostic perfluorohexane nanocapsules co encapsulating a drug for precision delivery using focused ultrasound. PMID- 28986301 TI - Sustained antimicrobial activity and reduced toxicity of oxidative biocides through biodegradable microparticles. AB - : The spread of antibiotic-resistant pathogens requires new treatments. Small molecule precursor compounds that produce oxidative biocides with well established antimicrobial properties could provide a range of new therapeutic products to combat resistant infections. The aim of this study was to investigate a novel biomaterials-based approach for the manufacture, targeted delivery and controlled release of a peroxygen donor (sodium percarbonate) combined with an acetyl donor (tetraacetylethylenediamine) to deliver local antimicrobial activity via a dynamic equilibrium mixture of hydrogen peroxide and peracetic acid. Entrapment of the pre-cursor compounds into hierarchically structured degradable microparticles was achieved using an innovative dry manufacturing process involving thermally induced phase separation (TIPS) that circumvented compound decomposition associated with conventional microparticle manufacture. The microparticles provided controlled release of hydrogen peroxide and peracetic acid that led to rapid and sustained killing of multiple drug-resistant organisms (methicillin-resistant Staphylococcus aureus and carbapenem-resistant Escherichia coli) without associated cytotoxicity in vitro nor intracutaneous reactivity in vivo. The results from this study demonstrate for the first time that microparticles loaded with acetyl and peroxygen donors retain their antimicrobial activity whilst eliciting no host toxicity. In doing so, it overcomes the detrimental effects that have prevented oxidative biocides from being used as alternatives to conventional antibiotics. STATEMENT OF SIGNIFICANCE: The manuscript explores a novel approach to utilize the antimicrobial activity of oxidative species for sustained killing of multiple drug-resistant organisms without causing collateral tissue damage. The results demonstrate, for the first time, the ability to load pre-cursor compounds into porous polymeric structures that results in their release and conversion into oxidative species in a controlled manner. Until now, the use of oxidative species has not been considered as a candidate therapeutic replacement for conventional antibiotics due to difficulties associated with handling during manufacture and controlling sustained release without causing undesirable tissue damage. The ultimate impact of the research could be the creation of new materials-based anti-infective chemotherapeutic agents that have minimal potential for giving rise to antimicrobial resistance. PMID- 28986302 TI - Activation of Nrf2 might reduce oxidative stress in human granulosa cells. AB - Nuclear factor-E2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1)-antioxidant response element (ARE) signaling pathway is one of the most important defense mechanisms against oxidative stress (OS). It is well documented that equilibration status of OS plays fundamental roles in human reproductive medicine, and the physiological role of Nrf2 in ovarian granulosa cells (GCs) has not been determined yet. Herein we aimed to study the function of Nrf2 in GCs. Human ovarian tissues were subjected to immunohistochemistry to localize Nrf2 and Keap1 and we detected the expression of Nrf2 and Keap1 in the human GCs. Human luteinized GCs were isolated and cultured, and hydrogen peroxide (H2O2) or Dimethylfumarates (DMF), an activator of Nrf2, were added to GCs to analyze the relationship between Nrf2 and antioxidants by quantitative RT-PCR. The mRNA levels of Nrf2, catalase, superoxide dismutase 1 (SOD1), and 8-Oxoguanine DNA glycosylase (OGG1) were elevated by H2O2, and DMF treatment showed similar but pronounced effects through activation of Nrf2. To determine the relationship of Nrf2 and the generation of antioxidants, siRNAs were used and quantitative RT-PCR were conducted. Decreased expression of Nrf2 resulted in a decreased level of these antioxidant mRNA. Intracellular levels of ROS were investigated by fluorescence of 8-hydroxy-2'-deoxyguanosine and fluorescent dye, 2',7' dichlorodihydrofluorescein diacetate after H2O2 and/or DMF treatment, and DMF treatment quenched intracellular ROS generation by H2O2. These results show that activation of Nrf2 might lead to alleviate OS in human GCs, and this could provide novel insight to conquer the age-related fertility decline that is mainly attributed to the accumulation of aberrant OS. PMID- 28986303 TI - Corticotropin releasing hormone can selectively stimulate glucose uptake in corticotropinoma via glucose transporter 1. AB - BACKGROUND: Pre-operative detection of corticotropin (ACTH) secreting microadenomas causing Cushing's disease (CD) improves surgical outcomes. Current best magnetic resonance imaging fails to detect up to 40% of these microadenomas. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) is specific, but not sensitive in detecting corticotropinomas. Theoretically, secretagogue stimulation with corticotropin releasing hormone (CRH) could improve detection of adenomas with 18F-FDG PET. Previous attempts with simultaneous CRH stimulation have failed to demonstrate increased 18F-FDG uptake in corticotropinomas. We hypothesized that CRH stimulation leads to a delayed elevation in glucose uptake in corticotropinomas. METHODS: Clinical data was analyzed for efficacy of CRH in improving 18FDG-PET detection of corticotropinomas in CD. Glucose transporter 1 (GLUT1) immunoreactivity was performed on surgical specimens. Ex-vivo, viable cells from these tumors were tested for secretagogue effects (colorimetric glucose uptake), and for fate of intracellular glucose (glycolysis stress analysis). Validation of ex-vivo findings was performed with AtT-20 cells. RESULTS: CRH increased glucose uptake in human-derived corticotroph tumor cells and AtT-20, but not in normal murine or human corticotrophs (p < 0.0001). Continuous and intermittent (1 h) CRH exposure increased glucose uptake in AtT-20 with maximal effect at 4 h (p = 0.001). Similarly, CRH and 8-Br-cAMP led to robust GLUT1 upregulation and increased membrane translocation at 2 h, while fasentin suppressed baseline (p < 0.0001) and CRH-mediated glucose uptake. Expectedly, intra-operatively collected corticotropinomas demonstrated GLUT1 overexpression. Lastly, human derived corticotroph tumor cells demonstrated increased glycolysis and low glucose oxidation. CONCLUSION: Increased and delayed CRH-mediated glucose uptake differentially occurs in adenomatous corticotrophs. Delayed secretagogue-stimulated 18F-FDG PET could improve microadenoma detection. PMID- 28986304 TI - Molecular profiles of oxyphilic and chief cell parathyroid adenoma. AB - CONTEXT: Parathyroid adenomas may be composed of chief cells (conventional or water-clear), oxyphilic cells or a mixture of both cells. The molecular background is rarely studied. OBJECTIVE: To molecularly characterize parathyroid adenomas of different cell type composition. DESIGN: Chief and oxyphilic cell adenomas were compared in a cohort of 664 sporadic cases. Extensive analyses of parathyroid tissues were performed in subgroup. Gene expressions of known parathyroid-related genes were quantified by qRT-PCR. Protein expression profiles determined by liquid chromatography - tandem mass spectrometry (LC-MS/MS) were compared between each type of parathyroid adenomas. Selected proteins were analysed by Western blot and immunohistochemistry. RESULTS: Patients with oxyphilic cell adenoma were found to be older at the time of operation than chief cell adenoma cases but did not differ in gender, serum calcium or tumor weight. The gene expression of CASR, VDR, FGFR1, CYP27B1, CYP24A1, PTHLH, GCM2, NDUFA13, CDKN1B, MEN1 and CNND1 did not differ between the groups. VDR protein levels were weaker in oxyphilic adenomas. The proteomic studies identified a set of novel dysregulated proteins of interest such as nuclear receptor subfamily 2 group C member 2 (TR4), LIM domain only protein 3 (LMO3) and calcium-binding protein B (S100B). LMO3 and S100B showed higher expression in oxyphilic adenoma and may be involve in parathyroid tumorgenesis through the p53 pathway. TR4 showed different subcellular localisation between adenoma and normal rim. CONCLUSION: Chief and oxyphilic cell parathyroid adenomas have partly overlapping but also distinct molecular profiles. The calmodulin-eEF2K, TR4 and p53 pathways may be involved in the tumor development. PMID- 28986306 TI - Animal arms. PMID- 28986305 TI - High-throughput BioSorter quantification of relative mitochondrial content and membrane potential in living Caenorhabditis elegans. AB - Mitochondrial respiratory chain disease is caused by a wide range of individually rare genetic disorders that impair cellular energy metabolism. While fluorescence microscopy analysis of nematodes fed MitoTracker Green (MTG) and tetramethylrhodamine ethyl ester (TMRE) can reliably quantify relative mitochondrial density and membrane potential, respectively, in C. elegans models of mitochondrial dysfunction, it is a tedious process with limitations in the number and age of animals that can be studied. A novel, large particle, flow cytometry-based method reported here accelerates and automates the relative quantitation of mitochondrial physiology in nematode populations. Relative fluorescence profiles of nematode populations co-labeled with MTG and TMRE were obtained and analyzed by BioSorter (Union Biometrica). Variables tested included genetic mutation (wild-type N2 Bristol versus nuclear-encoded respiratory chain complex I mutant gas-1(fc21) worms), animal age (day 1 versus day 4 adults), classical respiratory chain inhibitor and uncoupler effects (oligomycin, FCCP), and pharmacologic therapy duration (24h versus 96h treatments with glucose or nicotinic acid). A custom MATLAB script, which can be run on any computer with MATLAB runtime, was written to automatically quantify and analyze results in large animal populations. BioSorter analysis independently validated relative MTG and TMRE changes that we had previously performed by fluorescence microscopy in a variety of experimental conditions, with notably greater animal population sizes and substantially reduced experimental time. Older, fragile animal populations that are difficult to study by microscopy approaches were readily amenable to analysis with the BioSorter method. Overall, this high-throughput method enables efficient relative quantitation of in vivo mitochondrial physiology over time in a living animal in response to gene mutations and candidate therapies, which can be used to accelerate the translation of basic research into optimization of clinical therapies for mitochondrial disease. PMID- 28986307 TI - Interleukin-1beta and tumor necrosis factor-alpha augment acidosis-induced rat articular chondrocyte apoptosis via nuclear factor-kappaB-dependent upregulation of ASIC1a channel. AB - The acute-phase proinflammatory cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) demonstrate high-level expression and pleiotropic biological effects, and contribute to the progression and persistence of rheumatoid arthritis (RA). Acid hydrarthrosis is also an important pathological characteristic of RA, and the acid-sensing ion channel 1a (ASIC1a) plays a critical role in acidosis-induced chondrocyte cytotoxicity. However, the roles of IL-1beta and TNF-alpha in acid-induced apoptosis of chondrocytes remain unclear. Rat adjuvant arthritis and primary articular chondrocytes were used as in vivo and in vitro model systems, respectively. ASIC1a expression in articular cartilage was increased and highly colocalized with nuclear factor (NF)-kappaB expression in vivo. IL-1beta and TNF-alpha could upregulate ASIC1a expression. These cytokines activated mitogen-activated protein kinase and NF-kappaB pathways in chondrocytes, while the respective inhibitors of these signaling pathways could partially reverse the ASIC1a upregulation induced by IL-1beta and TNF alpha. Dual luciferase and gel-shift assays and chromatin immunoprecipitation polymerase chain reaction demonstrated that IL-1beta and TNF-alpha enhanced ASIC1a promoter activity in chondrocytes by increasing NF-kappaB DNA-binding activities, which was in turn prevented by the NF-kappaB inhibitor ammonium pyrrolidinedithiocarbamate. IL-1beta and TNF-alpha also decreased cell viability but enhanced LDH release, intracellular Ca2+ concentration elevation, loss of mitochondrial membrane potential, cleaved PARP and cleaved caspase-3/9 expression, and apoptosis in acid-stimulated chondrocytes, which effects could be abrogated by the specific ASIC1a inhibitor psalmotoxin-1 (PcTX-1), ASIC1a-short hairpin RNA or calcium chelating agent BAPTA-AM. These results indicate that IL 1beta and TNF-alpha can augment acidosis-induced cytotoxicity through NF-kappaB dependent up-regulation of ASIC1a channel expression in primary articular chondrocytes. PMID- 28986309 TI - Farnesoid X receptor: A "homeostat" for hepatic nutrient metabolism. AB - The Farnesoid X receptor (FXR) is a nuclear receptor activated by bile acids (BAs). BAs are amphipathic molecules that serve as fat solubilizers in the intestine under postprandial conditions. In the post-absorptive state, BAs bind FXR in the hepatocytes, which in turn provides feedback signals on BA synthesis and transport and regulates lipid, glucose and amino acid metabolism. Therefore, FXR acts as a homeostat of all three classes of nutrients, fats, sugars and proteins. Here we re-analyze the function of FXR in the perspective of nutritional metabolism, and discuss the role of FXR in liver energy homeostasis in postprandial, post-absorptive and fasting/starvation states. FXR, by regulating nutritional metabolism, represses autophagy in conditions of nutrient abundance, and controls the metabolic needs of proliferative cells. In addition, FXR regulates inflammation via direct effects and via its impact on nutrient metabolism. These functions indicate that FXR is an attractive therapeutic target for liver diseases. PMID- 28986308 TI - n-3 Fatty acids combined with flavan-3-ols prevent steatosis and liver injury in a murine model of NAFLD. AB - Non-alcoholic fatty liver disease (NAFLD) affects 25% of adults and at present no licensed medication has been approved. Despite its complex patho-physiology, dietary strategies aiming at delaying or preventing NAFLD have taken a reductionist approach, examining the impact of single components. Accumulating evidence suggests that n-3 LC-PUFAs are efficacious in regulating lipogenesis and fatty acid oxidation. In addition, plant derived flavonoids are also emerging as a dietary strategy for NAFLD prevention, with efficacy attributed to their insulin sensitising and indirect antioxidant effects. Based on knowledge of their complementary molecular targets, we aimed to demonstrate that the combination of n-3 LC-PUFA (n-3) and flavan-3-ols (FLAV) prevents NAFLD. In a high-fat high fructose (HF/HFr) fed C57Bl/6J mouse model, the independent and interactive impact of n-3 and FLAV on histologically defined NAFLD, insulin sensitivity, weight gain, intestinal and hepatic gene expression, intestinal bile acids were examined. Only the combination of FLAV and n-3 (FLAVn-3) prevented steatosis as evidenced by a strong reduction in hepatocyte ballooning. While FLAV reduced body (-28-30%), adipose tissue (-45-50%) weights and serum insulin (-22-25%) as observed following an intra-peritoneal glucose tolerance test, n-3 downregulated the expression of Srebf1 and the lipogenic genes (Acaca, Fasn). Significant impacts of interventions on intestinal bile acid metabolism, farnesoid X receptor (Fxr) signalling in the intestine and liver, and hepatic expression of fatty acid transporters (Fabp4, Vldlr, Cd36) were also evident. FLAVn-3 may be a novel intervention for NAFLD. Future research should aim to demonstrate its efficacy in the prevention and treatment of human NAFLD. PMID- 28986310 TI - The SGK1 inhibitor EMD638683, prevents Angiotensin II-induced cardiac inflammation and fibrosis by blocking NLRP3 inflammasome activation. AB - Inflammation has emerged as a critical biological process contributing to hypertensive cardiac remodeling. Effective pharmacological treatments targeting the cardiac inflammatory response, however, are still lacking. Prior studies suggested that the serum- and glucocorticoid-inducible kinase (SGK1) plays a key role in inflammation and cardiac remodeling. Recently, a highly selective SGK1 inhibitor, EMD638683, was developed, though whether EMD638683 can prevent hypertension-induced cardiac fibrosis and the mechanisms by which this inhibitor may alter the disease process remain unknown. Using a murine Angiotension II (Ang II) infusion-induced hypertension model we found that EMD638683 treatment inhibited cardiac fibrosis and remodeling, with significant abatement of cardiac inflammation. EMD638683 was shown to suppress Ang II infusion-induced interleukin (IL)-1beta release, and substantially reduce nucleotide-binding oligomerization domain-like receptor with pyrin domain 3 (NLRP3) expression and caspase-1 activation in cardiac tissues. In vitro experiments revealed that EMD638683 ameliorated Ang II-stimulated IL-1beta secretion in macrophages by blocking NLRP3 inflammasome activation. By reducing IL-1beta production in macrophages, the transformation of fibroblasts to myofibroblasts was inhibited. The effects of EMD638683 on cardiac fibrosis were abolished by supplementation with exogenous IL 1beta. Administration of the NLRP3 inflammasome inhibitor MCC950 indicated that EMD638683 attenuated Ang II-induced cardiac inflammation and fibrosis by inhibiting the NLRP3 inflammasome/IL-1beta secretion axis. These findings indicate that the SGK1 inhibitor EMD638683 can negatively regulate NLRP3 inflammasome activation, and may represent a promising approach to the treatment of hypertensive cardiac damage. PMID- 28986311 TI - Glaucoma and the brain: Trans-synaptic degeneration, structural change, and implications for neuroprotection. AB - A recent hypothesis to enter the literature suggests that glaucoma is a neurodegenerative disease. The basis for this has been the finding of central nervous system changes in glaucoma patients on histology and neuroimaging. It is known that retinal ganglion cell pathology of any cause leads to anterograde and retrograde retinal ganglion cell degeneration, as well as trans-synaptic (transneuronal) anterograde degeneration. Trans-synaptic degeneration has been demonstrated in a range of optic neuropathies including optic nerve transection, optic neuritis, and hereditary optic neuropathies. More recently, similar changes have been confirmed in glaucoma patients using the neuroimaging techniques of voxel-based morphometry and diffusion tensor imaging. Some studies have reported brain changes in glaucoma outside the retino-geniculo-cortical pathway; however, these are preliminary and exploratory in nature. Further research is required to identify whether the degenerative brain changes in glaucoma are entirely secondary to the optic neuropathy or whether there is additional primary central nervous system pathology. This has critical implications for neuroprotective and regenerative treatment strategies and our basic understanding of glaucoma. PMID- 28986312 TI - Bilateral upper and lower eyelid margin swelling and madarosis due to lymphoma. AB - Over a 2-year period, swellings of all 4 eyelid margins developed in a 32-year old woman and was accompanied by complete loss of eyelashes. An inflammatory dermatologic condition was considered the most likely cause. A full-thickness right lower eyelid biopsy revealed a multinodular lymphoid tumor at the eyelid margin which immunophenotypically and genetically was diagnosed as an extranodal marginal zone lymphoma. The mode of presentation of the disease was considered to be most unusual, as was its B cell lineage, since the majority of primary cutaneous lymphomas are of T-cell origin. Systemic workup demonstrated bilateral involvement of the external auditory canals. PMID- 28986313 TI - Impact of Clostridium difficile infection caused by the NAP1/RT027 strain on severity and recurrence during an outbreak and transition to endemicity in a Mexican tertiary care center. AB - OBJECTIVES: To describe the clinical characteristics, outcomes, and factors associated with Clostridium difficile infection (CDI) due to ribotype 027 (RT027) and recurrence, including an outbreak period, with transition to endemicity. METHODS: A case-control study was performed. Clinical and demographic data were collected for patients with CDI during the period January 2008 to December 2015. Ribotyping of the isolates and PCR for toxin A, B, and binary were performed. RESULTS: Among 324 episodes of CDI, 27.7% were caused by RT027. Previous fluoroquinolone use (odds ratio (OR) 1.79, 95% confidence interval (CI) 1.01 3.17), previous gastrointestinal endoscopy (OR 2.17, 95% CI 1.29-3.65), chemotherapy (OR 0.43, 95% CI 0.19-0.95), and total enteral nutrition (OR 0.42, 95% CI 0.18-0.97) were associated with RT027. Age >65 years (OR 2.05, 95% CI 1.02 4.10), severe initial episode (OR 3.35, 95% CI 1.60-6.15), previous proton pump inhibitor use (OR 2.34, 95% CI 1.15-4.74), and continued fluoroquinolones (OR 3.08, 95% CI 1.11-8.51) were associated with recurrence. Among the non-RT027, 59.8% were not assigned by the ribotyping database and 50.7% presented binary toxin. CONCLUSIONS: In this population, CDI due to the RT027 strain was not associated with poorer outcomes. This study reinforces the importance of avoiding fluoroquinolones and PPIs to prevent recurrences. The presence of virulence factors among non-RT027 C. difficile strains underscores the importance of performing molecular epidemiology surveillance. PMID- 28986314 TI - Preemptive anti-cytomegalovirus therapy in high-risk (donor-positive, recipient negative cytomegalovirus serostatus) kidney transplant recipients. AB - OBJECTIVES: Universal prophylaxis and preemptive therapy are used to prevent cytomegalovirus (CMV) disease post-transplantation. Data regarding which strategy is superior are sparse, especially in high-risk recipients (donor CMV seropositive (D+) and recipient CMV seronegative (R-)). METHODS: This retrospective, single-center cohort study included recipients who underwent kidney transplantation between 2009 and 2015. The incidence of CMV infection/disease and patient and graft outcomes were analyzed and compared between high-risk recipients (D+/R-) and intermediate-risk recipients (D+/R+ or D /R+), all managed with preemptive therapy. RESULTS: Of 118 kidney transplant recipients, 21 were high-risk and 97 were intermediate-risk. Over a median follow up period of 3 years, asymptomatic CMV infection developed significantly more frequently in high-risk patients than in intermediate-risk patients (38.1% vs. 16.5%, p=0.04), and CMV disease developed in a similar manner (28.6% vs. 3.1%, p<0.01). Among high-risk patients, CMV infection developed within the first 3 months post-transplantation and CMV disease within the first 9 months post transplantation. Kaplan-Meier analysis showed no difference in the probability of mortality (log-rank p=0.63) or graft loss (log-rank p=0.50) between the patient groups. Graft rejection occurred more frequently in high-risk than in intermediate-risk patients, but the difference was not significant (log-rank p=0.24). CONCLUSIONS: These results suggest that further studies on universal prophylaxis in high-risk patients are needed to elucidate whether preventing CMV infection/disease during the early post-transplant period leads to better outcomes, especially in terms of reducing graft rejection. PMID- 28986315 TI - Evolution analysis of Dof transcription factor family and their expression in response to multiple abiotic stresses in Malus domestica. AB - As a family of transcription factors, DNA binding with one figure (Dof) proteins play important roles in various biological processes in plants. Here, a total of 60 putative apple (Malus domestica) Dof genes (MdDof) were identified and mapped to different chromosomes. Chromosomal distribution and synteny analysis indicated that the expansion of the MdDof genes came primarily from segmental and duplication events, and from whole genome duplication, which lead to more Dof members in apples than in other plants. All 60 MdDof genes were classified into thirteen groups, according to multiple sequence alignment and the phylogenetic tree constructed of Dof genes from apple, peach (Prunus persica), Arabidopsis and rice. Within each group, the members shared a similar exon/intron and motif compositions, although the sizes of the MdDof genes and encoding proteins were quite different. Several Dof genes from the apple and peach were identified to be homologues based on their close synteny relationship, which suggested that these genes bear similar functions. Half of the MdDof genes were randomly selected to determine their responses to different stresses. The majority of MdDof genes were quite sensitive to PEG, NaCl, cold and exogenous ABA treatment. Our results suggested that MdDof family members may play important roles in plant tolerance to abiotic stress. PMID- 28986316 TI - Presence of a consensus DNA motif at nearby DNA sequence of the mutation susceptible CG nucleotides. AB - Complexity in tissues affected by cancer arises from somatic mutations and epigenetic modifications in the genome. The mutation susceptible hotspots present within the genome indicate a non-random nature and/or a position specific selection of mutation. An association exists between the occurrence of mutations and epigenetic DNA methylation. This study is primarily aimed at determining mutation status, and identifying a signature for predicting mutation prone zones of tumor suppressor (TS) genes. Nearby sequences from the top five positions having a higher mutation frequency in each gene of 42 TS genes were selected from a cosmic database and were considered as mutation prone zones. The conserved motifs present in the mutation prone DNA fragments were identified. Molecular docking studies were done to determine putative interactions between the identified conserved motifs and enzyme methyltransferase DNMT1. Collective analysis of 42 TS genes found GC as the most commonly replaced and AT as the most commonly formed residues after mutation. Analysis of the top 5 mutated positions of each gene (210 DNA segments for 42 TS genes) identified that CG nucleotides of the amino acid codons (e.g., Arginine) are most susceptible to mutation, and found a consensus DNA "T/AGC/GAGGA/TG" sequence present in these mutation prone DNA segments. Similar to TS genes, analysis of 54 oncogenes not only found CG nucleotides of the amino acid Arg as the most susceptible to mutation, but also identified the presence of similar consensus DNA motifs in the mutation prone DNA fragments (270 DNA segments for 54 oncogenes) of oncogenes. Docking studies depicted that, upon binding of DNMT1 methylates to this consensus DNA motif (C residues of CpG islands), mutation was likely to occur. Thus, this study proposes that DNMT1 mediated methylation in chromosomal DNA may decrease if a foreign DNA segment containing this consensus sequence along with CG nucleotides is exogenously introduced to dividing cancer cells. PMID- 28986317 TI - Acute hypoxia stress induced abundant differential expression genes and alternative splicing events in heart of tilapia. AB - Hypoxia is one of the critical environmental stressors for fish in aquatic environments. Although accumulating evidences indicate that gene expression is regulated by hypoxia stress in fish, how genes undergoing differential gene expression and/or alternative splicing (AS) in response to hypoxia stress in heart are not well understood. Using RNA-seq, we surveyed and detected 289 differential expressed genes (DEG) and 103 genes that undergo differential usage of exons and splice junctions events (DUES) in heart of a hypoxia tolerant fish, Nile tilapia, Oreochromis niloticus following 12h hypoxic treatment. The spatio temporal expression analysis validated the significant association of differential exon usages in two randomly selected DUES genes (fam162a and ndrg2) in 5 tissues (heart, liver, brain, gill and spleen) sampled at three time points (6h, 12h, and 24h) under acute hypoxia treatment. Functional analysis significantly associated the differential expressed genes with the categories related to energy conservation, protein synthesis and immune response. Different enrichment categories were found between the DEG and DUES dataset. The Isomerase activity, Oxidoreductase activity, Glycolysis and Oxidative stress process were significantly enriched for the DEG gene dataset, but the Structural constituent of ribosome and Structural molecule activity, Ribosomal protein and RNA binding protein were significantly enriched only for the DUES genes. Our comparative transcriptomic analysis reveals abundant stress responsive genes and their differential regulation function in the heart tissues of Nile tilapia under acute hypoxia stress. Our findings will facilitate future investigation on transcriptome complexity and AS regulation during hypoxia stress in fish. PMID- 28986318 TI - Development and implementation of an advanced model predictive control system into continuous pharmaceutical tablet compaction process. AB - In the context of continuous pharmaceutical oral dosage manufacturing, a control system is essential to ensure that the critical quality attributes (CQAs) are maintained within the regulatory constraints by mitigating variations generated in upstream operations. Such a system is essential to the Quality by Design (QbD) paradigm shift, which can ensure that predefined end quality attributes are achieved within an optimal economic and time bracket. In this work, an advanced model predictive control (MPC) architecture integrated with a novel real-time tablet weight measurement method has been development and implemented into a continuous direct compaction tablet manufacturing pilot-plant. The proposed control architecture has the potential to control tablet weight and tablet breaking force simultaneously by systematically decoupling and cascading the control loops. The model predictive control algorithm was experimentally found to be superior to the PID (proportional, integral and derivative) controller and thus, can be utilized for a wide range of applications to improve the quality of pharmaceutical products in continuous manufacturing. The MPC was used to control main compression force and pre compression force using main compression height and fill depth respectively as the actuators. The introduction of this methodology leads to new ways of developing MPC models, tablet weight measurement methods and control strategies that enhance the manufacturability and quality of pharmaceutical tablets. PMID- 28986319 TI - Enhancing the viability of Lactobacillus rhamnosus GG after spray drying and during storage. AB - Increasing knowledge about the human microbiome has led to a growing awareness of the potential of applying probiotics to improve our health. The pharmaceutical industry shows an emerging interest in pharmaceutical formulations containing these beneficial microbes, the so-called pharmabiotics. An important manufacturing step is the drying of the probiotics, as this can increase the stability and shelf life of the finished pharmabiotic product. Unfortunately, drying also puts stress on microbial cells, thus causing a decrease in viability. We aimed to examine the effect of different drying media and protective excipients on the viability of the prototype probiotic strain Lactobacillus rhamnosus GG after spray drying and during subsequent storage for 28 weeks. The presence of phosphates in the drying medium showed to have a superior protective effect, especially during long-term storage at room temperature. Addition of lactose or trehalose resulted in significantly improved survival rates after drying as well as during long-term storage for the tested excipients. Both disaccharides are characterized by a high glass transition temperature. Maltodextrin showed less protective capacities compared to lactose and trehalose in all tested conditions. The usage of mannitol or dextran resulted in sticky powders and low yields, so further testing was not possible. In addition to optimizing the viability, future research will also explore the functionality of cellular probiotic components after spray drying in order to safeguard the probiotic activity of the formulated pharmabiotics. PMID- 28986320 TI - Sustained intrathecal therapeutic protein delivery using genetically transduced tissue implants in a freely moving rat model. AB - Systemic delivery of therapeutic proteins to the central nervous system (CNS) is challenging because of the blood-brain barrier restrictions. Direct intrathecal delivery is possible but does not produce stable concentrations. We are proposing an alternative approach for localized delivery into the CNS based on the Transduced Autologous Restorative Gene Therapy (TARGT) system. This system was previously developed using a gene therapy approach with dermal tissue implants. Lewis rat dermal tissue was transduced to secrete human EPO (hEPO). TARGT viability and function were retained following cryopreservation. Upon implantation into the rat cisterna magna, a mild inflammatory response was observed at the TARGT-brain interface throughout 21-day implantation. hEPO expression was verified immunohistochemically and by secreted levels in cerebrospinal fluid (CSF), serum, and in vitro post explant. Detectable CSF hEPO levels were maintained during the study. Serum hEPO levels were similar to rat and human basal serum levels. In vitro, the highest hEPO concentration was observed on day 1 post-explant culture and then remained constant for over 21days. Prolonged incubation within the cisterna magna had no negative impact on TARGT hEPO secretion. These promising results suggest that TARGTs could be utilized for targeted delivery of therapeutic proteins to the CNS. PMID- 28986321 TI - An optimized two-vial formulation lipid nanoemulsion of paclitaxel for targeted delivery to tumor. AB - The discovery of new intravenous drug delivery carrier for water-insoluble drug is a challenging task. In this paper, novel two-vial formulation of paclitaxel (PTX)-loaded lipid nanoemulsions (TPLEs) with particle sizes of 110nm (TPLE-1), 220nm (TPLE-2) and 380nm (TPLE-3), which were formed by mixing a PEG400 solution of PTX and 10% (w/w) blank lipid emulsions (BLEs) with different particle size prior to use, were developed and comparatively evaluated for their pharmaceutics, pharmacokinetics, biodistribution, in vitro and in vivo anticancer efficiency. Among them, TPLE-1 displayed higher PTX-loading, slower PTX-release and larger PTX-distribution in oil-phase, significantly reduced extraction by RES organs, increased tumor-uptake, showed stronger cytotoxicity against MCF-7 cells and more potent anticancer efficacy on MCF-7 tumor-bearing nude mice, and had greater plasma AUC0-infinity value, smaller plasma clearance (CL), longer mean residence time (MRT) and elimination half-life (T1/2) in SD rats. It also exhibited the same in vivo efficacy as Taxol(r) and even produced less hemolysis and intravenous irritation. Moreover, its LD50 was 4.3-fold higher than that of Taxol(r). All results demonstrate that TPLE-1 is a promising candidate drug due to its high tumor-accumulation and effectiveness, low toxicity, good safety and druggability in clinical application for the cancer therapy. PMID- 28986322 TI - Formulation development of SYN-004 (ribaxamase) oral solid dosage form, a beta lactamase to prevent intravenous antibiotic-associated dysbiosis of the colon. AB - SYN-004 (ribaxamase) delayed release drug product is a multi-particulate, hard capsule for oral delivery of a recombinant beta-lactamase enzyme designed to degrade beta-lactam antibiotics administered intravenously, and thus prevent colon dysbiosis. Here we describe the development of the SYN-004 enteric coated pellet formulation, which has been tested in multiple clinical trials. Since the SYN-004 drug substance is a buffered liquid, several binder excipients in different ratios were tested to facilitate binding of SYN-004 to sugar spheres. The binding systems were evaluated by droplet pre-evaluation and film casting tests. The most promising formulations were produced in small scale fluidized bed application runs and analyzed by dissolution tests and complementary analytical assays. Hydroxypropyl cellulose was selected as the preferred SYN-004 binding excipient. The formulation included a second, outer coat containing the enteric EUDRAGIT(r) L 30 D-55 polymer-based formulation to achieve gastric protection, and rapid SYN-004 release in the intestinal tract, when the pH rises above 5.5. Additional formulation improvements resulted in an increase in the SYN-004 load compared to a predecessor oral enzyme formulation (Ipsat P1A). Thus, a novel formulation and process for an orally administered enzyme was developed and used to manufacture drug product for clinical trials. PMID- 28986323 TI - Phenotypic and genotypic detection of beta-lactamases in Acinetobacter spp. isolates recovered from Lebanese patients over a 1-year period. AB - OBJECTIVES: The aim of this study was to determine the prevalence of beta lactamases in Acinetobacter spp. recovered from Lebanese patients over a 1-year period using phenotypic and molecular methods. METHODS: A total of 100 non duplicate consecutive Acinetobacter spp. isolates were collected from various clinical specimens. Antimicrobial susceptibility testing was performed by the disk diffusion method. Susceptibility to colistin, imipenem and meropenem was determined by broth microdilution. The beta-lactamase inhibitors phenylboronic acid, cloxacillin and ethylene diamine tetra-acetic acid (EDTA) were used for presumptive detection of KPC-type beta-lactamase, AmpC beta-lactamase and metallo beta-lactamase (MBL), respectively. Simplex PCR was conducted for molecular detection of beta-lactamases. Trilocus PCR typing was performed to determine the clonality of the isolates. RESULTS: Among the 100 Acinetobacter spp. isolates, 78% were resistant to imipenem and 84% to meropenem. Only one isolate was resistant to colistin by the microdilution method. Phenotypically, 23% of the isolates were presumptively diagnosed as producing extended-spectrum beta lactamase (ESBL), 15% as producing KPC and 4% MBL, whilst 5% were diagnosed as overproducing AmpC beta-lactamase. The blaOXA-51-like gene was detected in 99% of isolates, blaADC in 93%, blaOXA-23-like in 77% and blaOXA-24/40-like in 3%. Trilocus PCR identified 86% (82/95) of the Acinetobacter baumannii isolates as international clone II (IC II). CONCLUSIONS: A high rate of carbapenem resistance, with a predominance of OXA-23-like and IC II, was shown in this study. Moreover, the inhibitor-based method was shown not to be accurate for the prediction of carbapenemases in A. baumannii. PMID- 28986325 TI - An Emotional Go/No-Go fMRI study in adolescents with depressive symptoms following concussion. AB - BACKGROUND: Following concussion, adolescents may experience both poor inhibitory control and increased depressive symptoms. fMRI research suggests that adolescents with major depressive disorder have abnormal physiological responses in the frontostriatal pathway, and exhibit poorer inhibitory control in the presence of negatively-aroused images. The scarcity of information surrounding depression following concussion in adolescents makes it difficult to identify patients at risk of depression after injury. This is the first study to examine neural activity patterns in adolescents with post-concussive depressive symptoms. PURPOSE: To explore the effect of depressive symptoms on inhibitory control in adolescents with concussion in the presence of emotional stimuli using fMRI. METHODS: Using a prospective cohort design, 30 adolescents diagnosed with concussion between 10 and 17years were recruited. The Children's Depression Inventory questionnaire was used to divide participants into two groups: average or elevated levels of depressive symptoms. Participants completed an Emotional Go/No-Go task involving angry or neutral faces in a 3Telsa MRI scanner. RESULTS: Eleven participants had elevated depressive symptoms, of which 72% were hit in the occipital region of the head at the time of injury. fMRI results from the Emotional Go/No-Go task revealed activity patterns in the overall sample. Faces activated regions associated with both facial and cognitive processing. However, frontal regions that are usually associated with inhibitory control were not activated. Adolescents with elevated levels of depressive symptoms engaged more frontal lobe regions during the task than the average group. They also showed a trend towards worse symptoms following MRI scanning. CONCLUSIONS: Adolescents with elevated depressive symptoms engaged brain regions subserving evaluative processing of social interactions. This finding provides insight into the role the environment plays in contributing to the cognitive demands placed on adolescents recovering from concussion. PMID- 28986324 TI - The ubiquitin conjugating enzyme Ube2W regulates solubility of the Huntington's disease protein, huntingtin. AB - Huntington's disease (HD) is caused by a CAG repeat expansion that encodes a polyglutamine (polyQ) expansion in the HD disease protein, huntingtin (HTT). PolyQ expansion promotes misfolding and aggregation of mutant HTT (mHTT) within neurons. The cellular pathways, including ubiquitin-dependent processes, by which mHTT is regulated remain incompletely understood. Ube2W is the only ubiquitin conjugating enzyme (E2) known to ubiquitinate substrates at their amino (N) termini, likely favoring substrates with disordered N-termini. By virtue of its N terminal polyQ domain, HTT has an intrinsically disordered amino terminus. In studies employing immortalized cells, primary neurons and a knock-in (KI) mouse model of HD, we tested the effect of Ube2W deficiency on mHTT levels, aggregation and neurotoxicity. In cultured cells, deficiency of Ube2W activity markedly decreases mHTT aggregate formation and increases the level of soluble monomers, while reducing mHTT-induced cytotoxicity. Consistent with this result, the absence of Ube2W in HdhQ200 KI mice significantly increases levels of soluble monomeric mHTT while reducing insoluble oligomeric species. This study sheds light on the potential function of the non-canonical ubiquitin-conjugating enzyme, Ube2W, in this polyQ neurodegenerative disease. PMID- 28986326 TI - Event-related potentials during individual, cooperative, and competitive task performance differ in subjects with analytic vs. holistic thinking. AB - It has been presented that Western cultures (USA, Western Europe) are mostly characterized by competitive forms of social interaction, whereas Eastern cultures (Japan, China, Russia) are mostly characterized by cooperative forms. It has also been stated that thinking in Eastern countries is predominantly holistic and in Western countries analytic. Based on this, we hypothesized that subjects with analytic vs. holistic thinking styles show differences in decision making in different types of social interaction conditions. We investigated behavioural and brain-activity differences between subjects with analytic and holistic thinking during a choice reaction time (ChRT) task, wherein the subjects either cooperated, competed (in pairs), or performed the task without interaction with other participants. Healthy Russian subjects (N=78) were divided into two groups based on having analytic or holistic thinking as determined with an established questionnaire. We measured reaction times as well as event-related brain potentials. There were significant differences between the interaction conditions in task performance between subjects with analytic and holistic thinking. Both behavioral performance and physiological measures exhibited higher variance in holistic than in analytic subjects. Differences in amplitude and P300 latency suggest that decision making was easier for the holistic subjects in the cooperation condition, in contrast to analytic subjects for whom decision making based on these measures seemed to be easier in the competition condition. The P300 amplitude was higher in the individual condition as compared with the collective conditions. Overall, our results support the notion that the brains of analytic and holistic subjects work differently in different types of social interaction conditions. PMID- 28986327 TI - Anthropometrics and maturity status: A preliminary study of youth football head impact biomechanics. AB - CONTEXT: There is a paucity of head impact biomechanics research focusing on youth athletes. Little is known about how youth subconcussive head impact tolerances are related to physical size and maturation. OBJECTIVE: To examine the effects of age, anthropometric and maturational status variability on head impact biomechanics. DESIGN: Cross-sectional. SETTING: Outdoor youth football facilities in South Carolina. PARTICIPANTS: Thirty-four male recreational youth football players, 8 to 13yrs. INTERVENTIONS: Categorized by CDC standards, independent variables were: age, height, mass, BMI, and estimated peak height velocity (PHV). Participants wore a designated head impact sensor (xPatch) on their mastoid process during practices and games. MAIN OUTCOME MEASURES: Linear acceleration (g) and rotational acceleration (rad/s2). RESULTS: Boys in the older age category had a greater linear (F=17.72; P<0.001) and rotational acceleration (F=10.74; P<0.001) than those in the younger category. Post-PHV boys had higher linear (F=9.09, P=0.002) and rotational (F=5.57, P=0.018) accelerations than those who were pre-PHV. Rotational, but not linear acceleration differed by height category with lowest impacts found for the tallest category, whereas both linear and rotational accelerations by mass differences favored average and heavy categories. BMI overweight boys, had the greatest linear (F=5.25; P=0.011) and rotational acceleration (F=4.13; P=0.260) means. CONCLUSION: Post-PHV boys who were older, taller and had longer legs, but who were not heavier, had higher impacts perhaps due to the type of impacts sustained. Taller boys' heads are above their peers possibly encouraging hits in the torso region resulting in lower impact accelerations. Obese boys did not have sequential results compared to boys in the other BMI categories probably due to league rules, player position, and lack of momentum produced. PMID- 28986328 TI - Bridging the gap: Incorporating a semantic similarity measure for effectively mapping PubMed queries to documents. AB - The main approach of traditional information retrieval (IR) is to examine how many words from a query appear in a document. A drawback of this approach, however, is that it may fail to detect relevant documents where no or only few words from a query are found. The semantic analysis methods such as LSA (latent semantic analysis) and LDA (latent Dirichlet allocation) have been proposed to address the issue, but their performance is not superior compared to common IR approaches. Here we present a query-document similarity measure motivated by the Word Mover's Distance. Unlike other similarity measures, the proposed method relies on neural word embeddings to compute the distance between words. This process helps identify related words when no direct matches are found between a query and a document. Our method is efficient and straightforward to implement. The experimental results on TREC Genomics data show that our approach outperforms the BM25 ranking function by an average of 12% in mean average precision. Furthermore, for a real-world dataset collected from the PubMed(r) search logs, we combine the semantic measure with BM25 using a learning to rank method, which leads to improved ranking scores by up to 25%. This experiment demonstrates that the proposed approach and BM25 nicely complement each other and together produce superior performance. PMID- 28986329 TI - Detecting clinically related content in online patient posts. AB - Patients with chronic health conditions use online health communities to seek support and information to help manage their condition. For clinically related topics, patients can benefit from getting opinions from clinical experts, and many are concerned about misinformation and biased information being spread online. However, a large volume of community posts makes it challenging for moderators and clinical experts, if there are any, to provide necessary information. Automatically identifying forum posts that need validated clinical resources can help online health communities efficiently manage content exchange. This automation can also assist patients in need of clinical expertise by getting proper help. We present our results on testing text classification models that efficiently and accurately identify community posts containing clinical topics. We annotated 1817 posts comprised of 4966 sentences of an existing online diabetes community. We found that our classifier performed the best (F-measure: 0.83, Precision: 0.79, Recall:0.86) when using Naive Bayes algorithm, unigrams, bigrams, trigrams, and MetaMap Symantic Types. Training took 5 s. The classification process took a fraction of 1 s. We applied our classifier to another online diabetes community, and the results were: F-measure: 0.63, Precision: 0.57, Recall: 0.71. Our results show our model is feasible to scale to other forums on identifying posts containing clinical topic with common errors properly addressed. PMID- 28986330 TI - Renal and femoral venous blood flows are regulated by different mechanisms dependent on alpha-adrenergic receptor subtypes and nitric oxide in anesthetized rats. AB - Venous and arterial walls are responsive to sympathetic system and circulating substances, nevertheless, very few is known about the venous blood flow regulation simultaneously to arterial vascular beds. In this study, we compared the venous and arterial blood flow regulation in visceral and muscular beds upon injection of different doses of vasoactive drugs which act in arterial vascular beds. Anesthetized adult male Wistar rats underwent to right femoral artery and vein cannulation for hemodynamic recordings and infusion of drugs. Doppler flow probes were placed around the left renal artery and vein, and left femoral artery and vein to evaluate the changes in flood flow. Phenylephrine (PHE) injection (alpha1-adrenergic receptor agonist) elicited vasoconstriction in all arteries and veins. Intravenous prazosin (PZS) (1mg/kg, alpha1-adrenergic receptor blocker) caused renal artery vasodilation, but not in the other beds. Vasoconstrictor effect of PHE was abolished by PZS in all vascular beds, except in femoral vein. Phentolamine (PTL) injection (1mg/kg, alpha1/alpha2-adrenergic receptor blocker) produced renal artery vasodilation with no change in other beds. After PTL, the vasoconstriction evoked by PHE was abolished in all vascular beds. Sodium Nitroprusside (SNP), a nitric oxide donor, elicited vasodilation in all beds, and after PTL but not post PZS injection, SNP enhanced the vasodilatory effect in femoral vein. Our findings suggest that the vasoconstriction in renal and femoral veins is mediated by different subtypes of alpha-adrenoceptors. The nitric oxide-dependent vasodilation in femoral vein enhances when alpha2 adrenoceptors are not under stimulation, but not in the other vascular beds investigated. PMID- 28986331 TI - Expressional divergences of two desaturase genes determine the opposite ratios of two sex pheromone components in Helicoverpa armigera and Helicoverpa assulta. AB - The sympatric closely related species Helicoverpa armigera and Helicoverpa assulta use 97:3 and 7:93 of (Z)-11-hexadecenal and (Z)-9-hexadecenal, respectively, as their sex pheromone to find/locate correct sex mates. Moreover, (Z)-11-hexadecenyl alcohol and (Z)-9-hexadecenyl alcohol are more abundant in the pheromone gland of H. assulta than in that of H. armigera. To clarify the molecular basis of these differences, we sequenced the pheromone gland transcriptomes of the two species and compared the expression patterns of the candidate enzyme genes involved in the pheromone biosynthetic pathways by FPKM values and quantitative RT-PCR analysis. We found that the desaturase gene LPAQ expressed about 70 times higher in H. armigera than in H. assulta, whereas another desaturase gene NPVE expressed about 60 times higher in H. assulta than in H. armigera. We also observed significantly higher expression of the fatty acyl reductase (FAR) gene FAR1 and the aldehyde reductase (AR) gene AR3 in H. assulta than in H. armigera. Examination of the pheromone glands of the backcross offspring of their hybrids to H. assulta showed a positive linear correlation between the expression level of LPAQ and the amount of Z11-16:Ald and between the expression level of NPVE and the amount of Z9-16:Ald in the pheromone glands. Taken together, these data demonstrate that the expressional divergences of LPAQ and NPVE determine the opposite sex pheromone component ratios in the two species and the divergent expression of FAR1 and AR3 may account for the greater accumulation of alcohols in the pheromone gland of H. assulta. PMID- 28986332 TI - Anticonvulsant effects of Senna spectabilis on seizures induced by chemicals and maximal electroshock. AB - Senna spectabilis (Fabaceae) is one of the medicinal plants used in Cameroon by traditional healers to treat epilepsy, constipation, insomnia, anxiety. The present study aimed to investigate the anticonvulsant effects of Senna spectabilis decoction on seizures induced by maximal electroshock (MES), pentylenetetrazole (PTZ), pilocarpine (PC) and its possible action mechanisms in animal models using flumazenil (FLU), methyl-beta-carboline-3-carboxylate (BC) and bicuculline (BIC). Senna spectabilis decoction (106.5 and 213.0mg/kg) antagonized completely tonic-clonic hind limbs of mice induced by MES. The lowest plant dose (42.6mg/kg) provided 100% of protection against seizures induced by PTZ (70mg/kg). Administration of different doses of the plant decoction antagonized seizures induced by PC up to 75%, causing a dose dependent protection and reduced significantly the mortality rate induced by this convulsant. Both FLU and BC antagonize strongly the anticonvulsant effects of this plant and are unable to reverse totally diazepam or the plant decoction effects on inhibiting seizures. The animals did not present any sign of acute toxicity even at higher doses of the plant decoction. In conclusion, Senna spectabilis possesses an anticonvulsant activity. We showed that its decoction protects significantly mice against seizures induced by chemicals and MES, delays the onset time and reduces mortality rate in seizures-induced. It also appears that the oral administration of the decoction of S. spectabilis is more active than the intraperitoneal administration of the ethanolic extract on inhibiting seizures induced by MES and PTZ. Moreover, the plant decoction could interact with GABAA complex receptor probably on the GABA and benzodiazepines sites. PMID- 28986333 TI - Protective effect of Danhong Injection combined with Naoxintong Capsule on cerebral ischemia-reperfusion injury in rats. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Danhong Injection (DHI) and Naoxintong Capsule (NXT) are renowned traditional Chinese medicine in China. The drug combination of DHI and NXT is frequently applied for the treatment of cardiovascular and cerebrovascular diseases in clinic. However, there had been no pharmacological experiment studies of interaction between DHI and NXT. Due to the drug interactions, exploring their interaction profile is of great importance. MATERIAL AND METHODS: In this study, focal cerebral I/R injury in adult male Sprague-Dawley rats were induced by transient middle cerebral artery occlusion (tMCAO) for 1h followed by reperfusion. Rats were divided into 5 groups: sham group, ischemia reperfusion untreated group (IRU), DHI group (DHI 10mL/kg/d), NXT group (NXT 0.5g/kg/d), DHI plus NXT group (DHI-NXT, DHI 10mL/kg/d plus NXT 0.5g/kg/d). All drug-treated groups were respectively successive administrated for 7 days after ischemia/ reperfusion (I/R) injury. The effects on rat neurological function were estimated by neurological defect scores. Brain infarct volumes were determined based on 2, 3, 5-triphenyltetrazolium chloride (TTC) staining. Pathological changes in brain tissues were observed using hematoxylin and eosin (H&E) staining and transmission electron microscope (TEM). Levels of nitric oxide (NO), granulocyte colony-stimulating factor (G-CSF) and granulocyte macrophage colony-stimulating factor (GM-CSF) in serum were determined with enzyme-linked immunosorbent assay (ELISA). Immunohisto-chemistry and Western blot were used to detect the expressions of basic fibroblast growth factor (bFGF), von Willebrand factor-microvessel vascular density (vWF-MVD), vascular endothelial cell growth factor (VEGF), transforming growth factor-beta1 (TGF-beta1), angiogenin-1 (Ang-1), angiogenin-2 (Ang-2) and platelet derived growth factor (PDGF) at day 7 after ischemia/reperfusion (I/R) injury. RESULTS: Compared with IRU group and mono-therapy group (DHI group or NXT group), Danhong Injection combined with Naoxintong Capsule (DHI-NXT) group significantly ameliorated neurological deficits scores, infarct volume and pathological change, significantly decreased the overexpression of NO and the level of Ang-1, significantly increased the expressions of VEGF, Ang-2, G-CSF, GM-CSF, bFGF, PDGF, vWF, TGF-beta1. CONCLUSION: The protective benefits on rat brain against I/R injury were clearly produced when DHI and NXT were used in combination, which provided rational guidance for clinical combined application of DHI and NXT, and this protection maybe associated with the up-regulation expressions of the related chemokines and growth factors of angiogenesis. PMID- 28986334 TI - Chronic obstructive pulmonary disease as a risk factor for ventricular arrhythmias independent of left ventricular function. AB - BACKGROUND: The association between chronic obstructive pulmonary disease (COPD) and sudden cardiac death has not been fully elucidated. OBJECTIVE: The purpose of this study was to investigate whether decreased left ventricular ejection fraction (LVEF) can explain the increased rate of ventricular tachycardia (VT) in COPD. METHODS: This retrospective study included consecutive adult patients who underwent pulmonary function testing (PFT), Holter monitoring, and transthoracic echocardiography. COPD was correlated with the frequency of VT in a multivariate analysis that adjusted for known confounders including LVEF. Long-term all-cause mortality of patients with COPD and VT was examined. RESULTS: Of the 6351 patients included in this study (age 66 +/- 15 years; 48% woman; 92% Caucasian, LVEF 59% +/- 12%), 2800 (44%) had PFT indicative of COPD. VT was nearly twice as likely to occur during Holter monitoring in COPD patients (13% vs 23%; P <.001), and the severity of COPD correlated with the risk of VT (21% vs 28% vs 37% for mild-moderate, severe, and very severe COPD; P <.001). COPD and VT remained independently associated (P <.001) even after adjusting for LVEF, demographics, and comorbidities (age, sex, body mass index, hypertension, chronic kidney disease, coronary artery disease, cancer history, diabetes mellitus). COPD was associated with all-cause mortality independently of LVEF (P <.001). CONCLUSION: COPD patients are at higher risk for VT and mortality. This may not be fully attributed to the confounding effect of systolic heart failure measured by LVEF. Further studies are needed to explore the mechanistic interactions between VT and COPD in order to determine whether antiarrhythmic strategies would apply especially to patients with severe COPD. PMID- 28986335 TI - Mobile Health Apps in OB-GYN-Embedded Psychiatric Care: Commentary. AB - This paper explores the potential benefits of the use of mobile health (mHealth) apps in obstetrician-gynecologist (OB-GYN)-embedded psychiatric clinics in the United States. First, we highlight the increasing trend of integrating mental health care within the OB-GYN context. Second, we provide examples of successful uses of mHealth in the global health context and highlight the dearth of available research in the United States. Finally, we provide a summary of the shortcomings of currently available apps and describe the upcoming trial of a novel app currently underway at the Mother-Child Wellness Clinical and Research Center at Boston Medical Center. PMID- 28986336 TI - Defining Information Quality Into Health Websites: A Conceptual Framework of Health Website Information Quality for Educated Young Adults. AB - BACKGROUND: Today's health care environment encourages health care consumers to take an active role in managing their health. As digital natives, young educated adults do much of their health information management through the Internet and consider it a valid source of health advice. However, the quality of information on health websites is highly variable and dynamic. Little is known about the understandings and perceptions that young educated adults have garnered on the quality of information on health websites used for health care-related purposes. OBJECTIVE: To fill this gap, the aim of this study was to develop a conceptual framework of health website information quality with quality dimensions (ie, criteria) and associated quality drivers (ie, attributes) specified in the context of young educated adults' use of health websites for health care-related purposes. This aim was achieved by (1) identifying information quality dimensions of health websites from the perspective of young educated adults; (2) identifying the importance ratings of these quality dimensions; and (3) constructing a framework of health website information quality with quality dimensions and associated drivers specified in the context of young educated adults' use of health websites for health care-related purposes. METHODS: The study employed both qualitative and quantitative methods. Methods included semistructured group interviews and an individual quality assessment exercise grounded in visiting various websites and responding to Likert scale questions regarding the importance ratings of information quality dimensions and open-ended questions with specifying website quality drivers. Study participants included junior and senior undergraduate and graduate students in business, allied health, and public health majors. Qualitative, open-coding procedures were used to develop the conceptual framework reflecting the participants' means of assessing information quality on health websites. RESULTS: Five dimensions of information quality for health websites were identified: Completeness of information, Understandability of information, Relevance of information, Depth of information, and Accuracy of information. Completeness of information and Understandability of information were rated as the two most important quality dimensions by the study participants. Results indicated that these five information quality dimensions for health websites were supported by the following main driver themes: Content, Design, Links, Consumer resources, Search functionality, Supporting references, User focus, Content FAQ, Open access, Policy statements, and Site performance. CONCLUSIONS: This study contributes to the literature by developing a health website information quality conceptual framework with quality dimensions and associated drivers specified for a young educated adult population. The detailed quality drivers supporting the corresponding quality dimensions provide a rich picture of young educated adults' perceptions on health website information quality. This framework can be used to guide the development of health websites, as well as the foundation for a means to evaluate health information from existing health websites with young educated adults as the target audience. PMID- 28986337 TI - Improving Neuromuscular Monitoring and Reducing Residual Neuromuscular Blockade With E-Learning: Protocol for the Multicenter Interrupted Time Series INVERT Study. AB - BACKGROUND: Muscle relaxants facilitate endotracheal intubation under general anesthesia and improve surgical conditions. Residual neuromuscular blockade occurs when the patient is still partially paralyzed when awakened after surgery. The condition is associated with subjective discomfort and an increased risk of respiratory complications. Use of an objective neuromuscular monitoring device may prevent residual block. Despite this, many anesthetists refrain from using the device. Efforts to increase the use of objective monitoring are time consuming and require the presence of expert personnel. A neuromuscular monitoring e-learning module might support consistent use of neuromuscular monitoring devices. OBJECTIVE: The aim of the study is to assess the effect of a neuromuscular monitoring e-learning module on anesthesia staff's use of objective neuromuscular monitoring and the incidence of residual neuromuscular blockade in surgical patients at 6 Danish teaching hospitals. METHODS: In this interrupted time series study, we are collecting data repeatedly, in consecutive 3-week periods, before and after the intervention, and we will analyze the effect using segmented regression analysis. Anesthesia departments in the Zealand Region of Denmark are included, and data from all patients receiving a muscle relaxant are collected from the anesthesia information management system MetaVision. We will assess the effect of the module on all levels of potential effect: staff's knowledge and skills, patient care practice, and patient outcomes. The primary outcome is use of neuromuscular monitoring in patients according to the type of muscle relaxant received. Secondary outcomes include last recorded train-of-four value, administration of reversal agents, and time to discharge from the postanesthesia care unit as well as a multiple-choice test to assess knowledge. The e-learning module was developed based on a needs assessment process, including focus group interviews, surveys, and expert opinions. RESULTS: The e learning module was implemented in 6 anesthesia departments on 21 November 2016. Currently, we are collecting postintervention data. The final dataset will include data from more than 10,000 anesthesia procedures. We expect to publish the results in late 2017 or early 2018. CONCLUSIONS: With a dataset consisting of thousands of general anesthesia procedures, the INVERT study will assess whether an e-learning module can increase anesthetists' use of neuromuscular monitoring. TRIAL REGISTRATION: Clinicaltrials.gov NCT02925143; https://clinicaltrials.gov/ct2/show/NCT02925143 (Archived by WebCite(r) at http://www.webcitation.org/6s50iTV2x). PMID- 28986338 TI - A Smart Card-Based Electronic School Absenteeism System for Influenza-Like Illness Surveillance in Hong Kong: Design, Implementation, and Feasibility Assessment. AB - BACKGROUND: School-aged children have the highest incidence of respiratory virus infections each year, and transmission of respiratory viruses such as influenza virus can be a major concern in school settings. School absenteeism data have been employed as a component of influenza surveillance systems in some locations. Data timeliness and system acceptance remain as key determinants affecting the usefulness of a prospective surveillance system. OBJECTIVE: The aim of this study was to assess the feasibility of implementing an electronic school absenteeism surveillance system using smart card-based technology for influenza-like illness (ILI) surveillance among a representative network of local primary and secondary schools in Hong Kong. METHODS: We designed and implemented a surveillance system according to the Protocol for a Standardized information infrastructure for Pandemic and Emerging infectious disease Response (PROSPER). We employed an existing smart card-based education and school administration platform for data capture, customized the user interface, and used additional back end systems built for other downstream surveillance steps. We invited local schools to participate and collected absenteeism data by the implemented system. We compared temporal trend of the absenteeism data with data from existing community sentinel and laboratory surveillance data. RESULTS: We designed and implemented an ILI surveillance system utilizing smart card-based attendance tracking approach for data capture. We implemented the surveillance system in a total of 107 schools (including 66 primary schools and 41 secondary schools), covering a total of 75,052 children. The system successfully captured information on absences for 2 consecutive academic years (2012-2013 and 2013-2014). The absenteeism data we collected from the system reflected ILI activity in the community, with an upsurge in disease activity detected up to 1 to 2 weeks preceding other existing surveillance systems. CONCLUSIONS: We designed and implemented a novel smart card technology-based school absenteeism surveillance system. Our study demonstrated the feasibility of building a large-scale surveillance system riding on a routinely adopted data collection approach and the use of simple system enhancement to minimize workload implication and enhance system acceptability. Data from this system have potential value in supplementing existing sentinel influenza surveillance for situational awareness of influenza activity in the community. PMID- 28986339 TI - The Promise and Pitfalls of Using Crowdsourcing in Research Prioritization for Back Pain: Cross-Sectional Surveys. AB - BACKGROUND: The involvement of patients in research better aligns evidence generation to the gaps that patients themselves face when making decisions about health care. However, obtaining patients' perspectives is challenging. Amazon's Mechanical Turk (MTurk) has gained popularity over the past decade as a crowdsourcing platform to reach large numbers of individuals to perform tasks for a small reward for the respondent, at small cost to the investigator. The appropriateness of such crowdsourcing methods in medical research has yet to be clarified. OBJECTIVE: The goals of this study were to (1) understand how those on MTurk who screen positive for back pain prioritize research topics compared with those who screen negative for back pain, and (2) determine the qualitative differences in open-ended comments between groups. METHODS: We conducted cross sectional surveys on MTurk to assess participants' back pain and allow them to prioritize research topics. We paid respondents US $0.10 to complete the 24-point Roland Morris Disability Questionnaire (RMDQ) to categorize participants as those "with back pain" and those "without back pain," then offered both those with (RMDQ score >=7) and those without back pain (RMDQ <7) an opportunity to rank their top 5 (of 18) research topics for an additional US $0.75. We compared demographic information and research priorities between the 2 groups and performed qualitative analyses on free-text commentary that participants provided. RESULTS: We conducted 2 screening waves. We first screened 2189 individuals for back pain over 33 days and invited 480 (21.93%) who screened positive to complete the prioritization, of whom 350 (72.9% of eligible) did. We later screened 664 individuals over 7 days and invited 474 (71.4%) without back pain to complete the prioritization, of whom 397 (83.7% of eligible) did. Those with back pain who prioritized were comparable with those without in terms of age, education, marital status, and employment. The group with back pain had a higher proportion of women (234, 67.2% vs 229, 57.8%, P=.02). The groups' rank lists of research priorities were highly correlated: Spearman correlation coefficient was .88 when considering topics ranked in the top 5. The 2 groups agreed on 4 of the top 5 and 9 of the top 10 research priorities. CONCLUSIONS: Crowdsourcing platforms such as MTurk support efforts to efficiently reach large groups of individuals to obtain input on research activities. In the context of back pain, a prevalent and easily understood condition, the rank list of those with back pain was highly correlated with that of those without back pain. However, subtle differences in the content and quality of free-text comments suggest supplemental efforts may be needed to augment the reach of crowdsourcing in obtaining perspectives from patients, especially from specific populations. PMID- 28986340 TI - A Call to Digital Health Practitioners: New Guidelines Can Help Improve the Quality of Digital Health Evidence. AB - BACKGROUND: Despite the rapid proliferation of health interventions that employ digital tools, the evidence on the effectiveness of such approaches remains insufficient and of variable quality. To address gaps in the comprehensiveness and quality of reporting on the effectiveness of digital programs, the mHealth Technical Evidence Review Group (mTERG), convened by the World Health Organization, proposed the mHealth Evidence Reporting and Assessment (mERA) checklist to address existing gaps in the comprehensiveness and quality of reporting on the effectiveness of digital health programs. OBJECTIVE: We present an overview of the mERA checklist and encourage researchers working in the digital health space to use the mERA checklist for reporting their research. METHODS: The development of the mERA checklist consisted of convening an expert group to recommend an appropriate approach, convening a global expert review panel for checklist development, and pilot-testing the checklist. RESULTS: The mERA checklist consists of 16 core mHealth items that define what the mHealth intervention is (content), where it is being implemented (context), and how it was implemented (technical features). Additionally, a 29-item methodology checklist guides authors on reporting critical aspects of the research methodology employed in the study. We recommend that the core mERA checklist is used in conjunction with an appropriate study-design specific checklist. CONCLUSIONS: The mERA checklist aims to assist authors in reporting on digital health research, guide reviewers and policymakers in synthesizing evidence, and guide journal editors in assessing the completeness in reporting on digital health studies. An increase in transparent and rigorous reporting can help identify gaps in the conduct of research and understand the effects of digital health interventions as a field of inquiry. PMID- 28986341 TI - Computerized Decision Aids for Shared Decision Making in Serious Illness: Systematic Review. AB - BACKGROUND: Shared decision making (SDM) is important in achieving patient centered care. SDM tools such as decision aids are intended to inform the patient. When used to assist in decision making between treatments, decision aids have been shown to reduce decisional conflict, increase ease of decision making, and increase modification of previous decisions. OBJECTIVE: The purpose of this systematic review is to assess the impact of computerized decision aids on patient-centered outcomes related to SDM for seriously ill patients. METHODS: PubMed and Scopus databases were searched to identify randomized controlled trials (RCTs) that assessed the impact of computerized decision aids on patient centered outcomes and SDM in serious illness. Six RCTs were identified and data were extracted on study population, design, and results. Risk of bias was assessed by a modified Cochrane Risk of Bias Tool for Quality Assessment of Randomized Controlled Trials. RESULTS: Six RCTs tested decision tools in varying serious illnesses. Three studies compared different computerized decision aids against each other and a control. All but one study demonstrated improvement in at least one patient-centered outcome. Computerized decision tools may reduce unnecessary treatment in patients with low disease severity in comparison with informational pamphlets. Additionally, electronic health record (EHR) portals may provide the opportunity to manage care from the home for individuals affected by illness. The quality of decision aids is of great importance. Furthermore, satisfaction with the use of tools is associated with increased patient satisfaction and reduced decisional conflict. Finally, patients may benefit from computerized decision tools without the need for increased physician involvement. CONCLUSIONS: Most computerized decision aids improved at least one patient centered outcome. All RCTs identified were at a High Risk of Bias or Unclear Risk of Bias. Effort should be made to improve the quality of RCTs testing SDM aids in serious illness. PMID- 28986342 TI - Challenges of incentivising patient centred care. PMID- 28986343 TI - Treatment of experimental autoimmune uveoretinitis with intravitreal injection of infliximab encapsulated in liposomes. AB - AIMS: To evaluate the safety and efficacy of intravitreal injection of liposomes encapsulating infliximab in experimental autoimmune uveoretinitis (EAU) rats. METHODS: Liposomes containing infliximab were prepared and characterised for mean particle size, entrapment efficiency, polydispersity index (PDI) and zeta potential. In vitro release profile and the stability of infliximab-lip were evaluated. EAU rats were intravitreally injected with saline, infliximab, infliximab-lip or unloaded liposomes. Clinical signs and ocular histological sections were graded. Infliximab concentrations were determined with competitive ELISA. Safety of the intravitreal injections was evaluated by electroretinography (ERG) and histopathological examination. Retinal biodistribution and clearance of rhodamine-conjugated liposomes containing infliximab were evaluated with a laser scanning confocal microscope. RESULTS: The mean particle size of infliximab liposomes was 351.3+/-58 nm and entrapment efficiency was 90.65%+/-2.68%. PDI and zeta potential of infliximab liposomes were 0.386 and -20.8+/-9.78 mV, respectively. Stability test data showed that the infliximab-lip was stable for 60 days at room temperature. In EAU rats, intravitreal injection of infliximab and infliximab-lip greatly reduced intraocular inflammation determined by clinical scores and histopathological analyses (n=4). The mean concentrations of infliximab decreased quickly in infliximab injection group and were lower than those in infliximab-lip injection group (n=4 eyes, p<0.05 after 3 days post injection). No retinal toxic effects were detected after intravitreal injection of infliximab-lip in ERG (n=4 rats, p>0.05) and histopathological sections compared with normal rats. Confocal microscopy showed that fluorescent liposomes were observed in almost every layer of the retina and remained detectable for >30 days after injection. CONCLUSIONS: Intravitreal injection of liposomal infliximab can prolong the persistence of the drug in vitreous body and demonstrated a satisfactory safety and significant therapeutic potentials in EAU. The use of biodegradable particles for therapeutic antibody delivery may provide a promising approach for the treatment of ocular diseases. PMID- 28986345 TI - Puerto Rico's morgues full of uncounted bodies as hurricane death toll continues to rise. PMID- 28986344 TI - NK cell recovery after haploidentical HSCT with posttransplant cyclophosphamide: dynamics and clinical implications. AB - The use of posttransplant cyclophosphamide (PT-Cy) as graft-versus-host disease (GVHD) prophylaxis has revolutionized haploidentical hematopoietic stem cell transplantation (HSCT), allowing safe infusion of unmanipulated T cell-replete grafts. PT-Cy selectively eliminates proliferating alloreactive T cells, but whether and how it affects natural killer (NK) cells and their alloreactivity is largely unknown. Here we characterized NK cell dynamics in 17 patients who received unmanipulated haploidentical grafts, containing high numbers of mature NK cells, according to PT-Cy-based protocols in 2 independent centers. In both series, we documented robust proliferation of donor-derived NK cells immediately after HSCT. After infusion of Cy, a marked reduction of proliferating NK cells was evident, suggesting selective purging of dividing cells. Supporting this hypothesis, proliferating NK cells did not express aldehyde dehydrogenase and were killed by Cy in vitro. After ablation of mature NK cells, starting from day 15 after HSCT and favored by the high levels of interleukin-15 present in patients' sera, immature NK cells (CD62L+NKG2A+KIR-) became highly prevalent, possibly directly stemming from infused hematopoietic stem cells. Importantly, also putatively alloreactive single KIR+ NK cells were eliminated by PT-Cy and were thus decreased in numbers and antileukemic potential at day 30 after HSCT. As a consequence, in an extended series of 99 haplo-HSCT with PT-Cy, we found no significant difference in progression-free survival between patients with or without predicted NK alloreactivity (42% vs 52% at 1 year, P = NS). Our data suggest that the majority of mature NK cells infused with unmanipulated grafts are lost upon PT-Cy administration, blunting NK cell alloreactivity in this transplantation setting. PMID- 28986346 TI - Sharing resources online is central to medical research and teaching. PMID- 28986347 TI - Relation between family physician retention and avoidable hospital admission in Newfoundland and Labrador: a population-based cross-sectional study. AB - BACKGROUND: Physician turnover, involving physicians' leaving clinical practice in a specific area, may disrupt continuity of care, leading to poorer health outcomes and greater use of health care services. The purpose of this study was to investigate the relation between family physician retention and avoidable hospital admission for ambulatory-care-sensitive conditions. METHODS: We conducted a population-based cross-sectional study using provincial health administrative data for residents of Newfoundland and Labrador who held a provincial health card between 2001 and 2009. Five-year family physician retention was calculated by regional economic zone, and residents within economic zones were grouped into tertiles based on physician retention level. We compared hospital admission for ambulatory-care-sensitive conditions among tertiles while adjusting for covariates. RESULTS: For 475 691 residents of the province, there was a negative relation between physician retention and hospital admission for ambulatory-care-sensitive conditions: residents of areas with moderate or low physician retention had admission rates that were 16.5% (95% confidence interval [CI) 12.6%-20.4%) and 19.9% (95% CI 15.2%-24.7%) higher, respectively, compared to areas with high retention. No relation was found when analysis was limited to those aged 65 years or more. INTERPRETATION: The findings suggest that high physician retention is associated with lower rates of hospital admission for ambulatory-care-sensitive conditions even after control for other factors. This is consistent with our hypothesis that physician turnover acts to disrupt continuity of care, resulting in higher admission rates. PMID- 28986349 TI - Automated left heart chamber volumetric assessment using three-dimensional echocardiography in Chinese adolescents. AB - BACKGROUND: Several studies have reported the accuracy and reproducibility of HeartModel for automated determination of three-dimensional echocardiography (3DE)-derived left heart volumes and left ventricular (LV) ejection fraction (LVEF) in adult patients. However, it remains unclear whether this automated adaptive analytics algorithm, derived from a 'training' population, can encompass adequate echo images in Chinese adolescents. OBJECTIVES: The aim of our study was to explore the accuracy of HeartModel in adolescents compared with expert manual three-dimensional (3D) echocardiography. METHODS: Fifty-three Chinese adolescent subjects with or without heart disease underwent 3D echocardiographic imaging with an EPIQ system (Philips). 3D cardiac volumes and LVEF obtained with the automated HeartModel program were compared with manual 3D echocardiographic measurements by an experienced echocardiographer. RESULTS: There was strong correlation between HeartModel and expert manual 3DE measurements (r = 0.875 0.965, all P < 0.001). Automated LV and left atrial (LA) volumes were slightly overestimated when compared to expert manual measurements, while LVEF showed no significant differences from the manual method. Importantly, the intra- and inter observer variability of automated 3D echocardiographic model was relatively low (<1%), surpassing the manual approach (3.5-17.4%), yet requiring significantly less analyzing time (20 +/- 7 vs 177 +/- 30 s, P < 0.001). CONCLUSION: Simultaneous quantification of left heart volumes and LVEF with the automated HeartModel program is rapid, accurate and reproducible in Chinese adolescent cohort. Therefore, it has a potential to bring 3D echocardiographic assessment of left heart chamber volumes and function into busy pediatric practice. PMID- 28986348 TI - Emerging Trends in Family History of Breast Cancer and Associated Risk. AB - Background: Increase in breast cancer incidence associated with mammography screening diffusion may have attenuated risk associations between family history and breast cancer.Methods: The proportions of women ages 40 to 74 years reporting a first-degree family history of breast cancer were estimated in the Breast Cancer Surveillance Consortium cohort (BCSC: N = 1,170,900; 1996-2012) and the Collaborative Breast Cancer Study (CBCS: cases N = 23,400; controls N = 26,460; 1987-2007). Breast cancer (ductal carcinoma in situ and invasive) relative risk estimates and 95% confidence intervals (CI) associated with family history were calculated using multivariable Cox proportional hazard and logistic regression models.Results: The proportion of women reporting a first-degree family history increased from 11% in the 1980s to 16% in 2010 to 2013. Family history was associated with a >60% increased risk of breast cancer in the BCSC (HR, 1.61; 95% CI, 1.55-1.66) and CBCS (OR, 1.64; 95% CI, 1.57-1.72). Relative risks decreased slightly with age. Consistent trends in relative risks were not observed over time or across stage of disease at diagnosis in both studies, except among older women (ages 60-74) where estimates were attenuated from about 1.7 to 1.3 over the last 20 years (P trend = 0.08 for both studies).Conclusions: Although the proportion of women with a first-degree family history of breast cancer increased over time and by age, breast cancer risk associations with family history were nonetheless fairly constant over time for women under age 60.Impact: First-degree family history of breast cancer remains an important breast cancer risk factor, especially for younger women, despite its increasing prevalence in the mammography screening era. Cancer Epidemiol Biomarkers Prev; 26(12); 1753-60. (c)2017 AACR. PMID- 28986350 TI - Post-myocardial infarction left ventricular pseudoaneurysm diagnosed incidentally by echocardiography. AB - : A 54-year-old male developed a left ventricular pseudoaneurysm (Ps) along the lateral wall of the left ventricle (LV), which was diagnosed incidentally by two dimensional transthoracic echocardiography (2DTTE) 6 months after an acute myocardial infarction. Color flow imaging (CFI) showed blood flow from the LV into the aneurysmal cavity and invasive coronary angiography revealed sub occlusion of the circumflex artery. A complementary study using cardiovascular magnetic resonance (CMR) confirmed a dilated left ventricle with depressed ejection fraction, thin dyskinetic anterolateral and inferolateral walls, a Ps adjacent to the lateral wall of the LV contained by the pericardium and blood passing in and out through a small defect in the LV mid-anterolateral wall. Late gadolinium-enhanced imaging demonstrated transmural myocardial infarction in the lateral wall and delayed enhancement of the pericardium, which formed the walls of the Ps. A conservative approach was adopted in this case, optimizing the patient's heart failure medications, including cardioselective beta-blocker agents, angiotensin-converting enzyme inhibitors, spironolactone and chronic anticoagulation therapy because of a high risk of ischemic stroke in these patients. At the 13-month follow-up, the patient remained stable with New York Heart Association class II heart failure. In conclusion, 2DTTE and CFI seem to be suitable initial methods for diagnosing Ps of the LV, but CMR is an excellent complementary method for characterizing further this cardiac entity. Furthermore, the long-term outcome of patients with Ps of the LV who are treated medically appears to be relatively benign. LEARNING POINTS: Left ventricular pseudoaneurysms are uncommon but severe complications of acute myocardial infarction.Transthoracic two-dimensional echocardiography and CFI are suitable non-invasive diagnostic methods for diagnosing left ventricular pseudoaneurysms.Cardiac magnetic resonance is an excellent complementary method, as it offers additional information for further characterization of this cardiac complication.Despite the fact that surgery is the treatment of choice to avoid a risk of fatal rupture, the long-term outcome of patients with left ventricular pseudoaneurysm who are treated medically appears to be relatively benign. PMID- 28986352 TI - US health secretary quits over improper use of aircraft. PMID- 28986351 TI - The Council of Europe should not reaffirm the ban on germline genome editing in humans. PMID- 28986353 TI - When is bronchiolitis not bronchiolitis? PMID- 28986357 TI - Excess omega-6 fatty acids influx in aging drives metabolic dysregulation, electrocardiographic alterations, and low-grade chronic inflammation. AB - Maintaining a balance of omega-6 and omega-3 fatty acids is essential for cardiac health. Current omega-6 and omega-3 fatty acids in the American diet have shifted from the ideal ratio of 2:1 to almost 20:1; while there is a body of evidence that suggests the negative impact of such a shift in younger organisms, the underlying age-related metabolic signaling in response to the excess influx of omega-6 fatty acids is incompletely understood. In the present study, young (6 mo old) and aging (>=18 mo old) mice were fed for 2 mo with a omega-6-enriched diet. Excess intake of omega-6 enrichment decreased the total lean mass and increased nighttime carbohydrate utilization, with higher levels of cardiac cytokines indicating low-grade chronic inflammation. Dobutamine-induced stress tests displayed an increase in PR interval, a sign of an atrioventricular defect in omega-6-fed aging mice. Excess omega-6 fatty acid intake in aging mice showed decreased 12-lipoxygenase with a concomitant increase in 15-lipoxygenase levels, resulting in the generation of 15( S)-hydroxyeicosatetraenoic acid, whereas cyclooxygenase-1 and -2 generated prostaglandin E2, leukotriene B4, and thromboxane B2. Furthermore, excessive omega-6 fatty acids led to dysregulated nuclear erythroid 2-related factor 2/antioxidant-responsive element in aging mice. Moreover, omega-6 fatty acid-mediated changes were profound in aging mice with respect to the eicosanoid profile while minimal changes were observed in the size and shape of cardiomyocytes. These findings provide compelling evidence that surplus consumption of omega-6 fatty acids, coupled with insufficient intake of omega-3 fatty acids, is linked to abnormal changes in ECG. These manifestations contribute to functional deficiencies and expansion of the inflammatory mediator milieu during later stages of aging. NEW & NOTEWORTHY Aging has a profound impact on the metabolism of fatty acids to maintain heart function. The excess influx of omega-6 fatty acids in aging perturbed electrocardiography with marked signs of inflammation and a dysregulated oxidative-redox balance. Thus, the quality and quantity of fatty acids determine the cardiac pathology and energy utilization in aging. PMID- 28986358 TI - Pulmonary vasodilation by phosphodiesterase 5 inhibition is enhanced and nitric oxide independent in early pulmonary hypertension after myocardial infarction. AB - Myocardial infarction (MI) may result in pulmonary hypertension (PH). Inhibition of phosphodiesterase 5 (PDE5), the enzyme responsible for the breakdown of cGMP in vascular smooth muscle, has become part of the contemporary therapeutic armamentarium for pulmonary arterial hypertension and may also be beneficial for PH secondary to MI. Nitric oxide (NO) is an important activator of cGMP synthesis and can be enhanced in early PH and decreased in severe PH. In the present study, we investigated if PDE5 inhibition ameliorates pulmonary hemodynamics in swine with PH secondary to MI and whether NO is essential. The PDE5 inhibitor EMD360527 was administered in awake, chronically instrumented swine with or without MI. At rest, PDE5 inhibition produced pulmonary vasodilation as evidenced by a decrease in pulmonary vascular resistance, which was more pronounced in MI ( n = 5) compared with normal swine ( n = 10, P <= 0.01) and was accompanied by an increase in stroke volume in MI swine. Both pulmonary vasodilation and increased stroke volume were maintained during exercise, suggesting that this therapy may improve exercise capacity in patients with PH secondary to MI. Interestingly, prior inhibition of NO significantly enhanced ( P <= 0.01) pulmonary vasodilation by PDE5 inhibition in both normal ( n = 8) and MI swine ( n = 5, P <= 0.05 vs. normal). This suggests that the increased vasodilator responses to PDE5 inhibition after MI were not due to an increase in NO-induced cGMP production. These observations indicate that PDE5 inhibition represents an interesting pharmacotherapeutic approach in early PH after a recent MI to prevent overt PH. NEW & NOTEWORTHY This research article is the first to describe that pulmonary vasodilation to phosphodiesterase 5 inhibition is enhanced and nitric oxide independent in resting and exercising swine with pulmonary hypertension as a result of myocardial infarction. This suggests that phosphodiesterase 5 inhibition can normalize pulmonary hemodynamics in postcapillary pulmonary hypertension after a recent myocardial infarction and may improve exercise capacity. PMID- 28986359 TI - Dual effects of hyperglycemia on endothelial cells and cardiomyocytes to enhance coronary LPL activity. AB - In the diabetic heart, there is excessive dependence on fatty acid (FA) utilization to generate ATP. Lipoprotein lipase (LPL)-mediated hydrolysis of circulating triglycerides is suggested to be the predominant source of FA for cardiac utilization during diabetes. In the heart, the majority of LPL is synthesized in cardiomyocytes and secreted onto cell surface heparan sulfate proteoglycan (HSPG), where an endothelial cell (EC)-releasable beta endoglycosidase, heparanase cleaves the side chains of HSPG to liberate LPL for its onward movement across the EC. EC glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 (GPIHBP1) captures this released enzyme at its basolateral side and shuttles it across to its luminal side. We tested whether the diabetes-induced increase of transforming growth factor-beta (TGF beta) can influence the myocyte and EC to help transfer LPL to the vascular lumen to generate triglyceride-FA. In response to high glucose and EC heparanase secretion, this endoglycosidase is taken up by the cardiomyocyte (Wang Y, Chiu AP, Neumaier K, Wang F, Zhang D, Hussein B, Lal N, Wan A, Liu G, Vlodavsky I, Rodrigues B. Diabetes 63: 2643-2655, 2014) to stimulate matrix metalloproteinase 9 expression and the conversion of latent to active TGF-beta. In the cardiomyocyte, TGF-beta activation of RhoA enhances actin cytoskeleton rearrangement to promote LPL trafficking and secretion onto cell surface HSPG. In the EC, TGF-beta signaling promotes mesodermal homeobox 2 translocation to the nucleus, which increases the expression of GPIHBP1, which facilitates movement of LPL to the vascular lumen. Collectively, our data suggest that in the diabetic heart, TGF-beta actions on the cardiomyocyte promotes movement of LPL, whereas its action on the EC facilitates LPL shuttling. NEW & NOTEWORTHY Endothelial cells, as first responders to hyperglycemia, release heparanase, whose subsequent uptake by cardiomyocytes amplifies matrix metalloproteinase-9 expression and activation of transforming growth factor-beta. Transforming growth factor-beta increases lipoprotein lipase secretion from cardiomyocytes and promotes mesodermal homeobox 2 to enhance glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1-dependent transfer of lipoprotein lipase across endothelial cells, mechanisms that accelerate fatty acid utilization by the diabetic heart. PMID- 28986360 TI - Exaggerated cardiovascular responses to treadmill running in rats with peripheral arterial insufficiency. AB - Patients with atherosclerotic peripheral artery disease have an augmented pressor response to treadmill walking, but the underlying mechanisms remain poorly understood and difficult to isolate because of the confounding presence of numerous cardiovascular risk factors. In the present study, we tested the hypothesis that a chronic deficit in muscle blood flow capacity would be sufficient to trigger an exaggerated pressor response to dynamic exercise. Sprague-Dawley rats (5 male and 5 female) were instrumented with radiotelemetry devices to measure the cardiovascular responses to treadmill running before and after bilateral femoral artery ligation, which has been previously shown to reduce the blood flow capacity of distal hindlimb muscles by >60%. Treadmill running evoked reproducible increases in mean arterial pressure (MAP) and heart rate (HR), which were significantly augmented 3 days after femoral artery ligation in both male rats [DeltaMAP: +10 +/- 1 (SE) vs. +18 +/- 3 mmHg and DeltaHR: +94 +/- 12 vs. +148 +/- 15 beats/min, P < 0.05] and female rats (DeltaMAP: +16 +/- 3 vs. +30 +/- 5 mmHg and DeltaHR: +128 +/- 20 vs. +178 +/- 19 beats/min, P < 0.05). Similar exaggerated MAP and HR responses were observed at repeated intervals between 3 and 65 days postligation. These findings indicate that a chronic deficit in muscle blood flow capacity is an important, persistent cause of the abnormal pressor and cardioaccelerator responses to dynamic exercise in both male and female rats with peripheral arterial insufficiency. NEW & NOTEWORTHY Using radiotelemetry to assess cardiovascular effects of exercise, we showed that femoral artery obstruction in male and female rats is an important, persistent cause of exaggerated pressor and cardioaccelerator responses to treadmill running. This translational model reproduces the abnormal cardiovascular response to exercise seen in patients with peripheral artery disease. Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/treadmill-bp-in-simulated-peripheral-artery disease/ . PMID- 28986362 TI - HDL protects against doxorubicin-induced cardiotoxicity in a scavenger receptor class B type 1-, PI3K-, and Akt-dependent manner. AB - Doxorubicin is a widely used chemotherapeutic with deleterious cardiotoxic side effects. HDL has been shown to protect cardiomyocytes in vitro against doxorubicin-induced apoptosis. Scavenger receptor class B type 1 (SR-B1), a high affinity HDL receptor, mediates cytoprotective signaling by HDL through Akt. Here, we assessed whether increased HDL levels protect against doxorubicin induced cardiotoxicity in vivo and in cardiomyocytes in culture and explored the intracellular signaling mechanisms involved, particularly the role of SR-B1. Transgenic mice with increased HDL levels through overexpression of human apolipoprotein A1 (apoA1Tg/Tg) and wild-type mice (apoA1+/+) with normal HDL levels were treated repeatedly with doxorubicin. After treatment, apoA1+/+ mice displayed cardiac dysfunction, as evidenced by reduced left ventricular end systolic pressure and +dP/d t, and histological analysis revealed cardiomyocyte atrophy and increased cardiomyocyte apoptosis after doxorubicin treatment. In contrast, apoA1Tg/Tg mice were protected against doxorubicin-induced cardiac dysfunction and cardiomyocyte atrophy and apoptosis. When SR-B1 was knocked out, however, overexpression of apoA1 did not protect against doxorubicin-induced cardiotoxicity. Using primary neonatal mouse cardiomyocytes and human immortalized ventricular cardiomyocytes in combination with genetic knockout, inhibitors, or siRNA-mediated knockdown, we demonstrated that SR-B1 is required for HDL-mediated protection of cardiomyocytes against doxorubicin-induced apoptosis in vitro via a pathway involving phosphatidylinositol 3-kinase and Akt1/2. Our findings provide proof of concept that raising apoA1 to supraphysiological levels can dramatically protect against doxorubicin-induced cardiotoxicity via a pathway that is mediated by SR-B1 and involves Akt1/2 activation in cardiomyocytes. NEW & NOTEWORTHY We have identified an important role for the scavenger receptor class B type 1 in facilitating high-density lipoprotein-mediated protection of cardiomyocytes against stress-induced apoptosis and shown that increasing plasma high-density lipoprotein protects against the deleterious side effects of the chemotherapeutic and cardiotoxic drug doxorubicin. PMID- 28986363 TI - Plastic surgeons report surge in reoperations for patients treated abroad. PMID- 28986361 TI - Regulating microRNA expression: at the heart of diabetes mellitus and the mitochondrion. AB - Type 2 diabetes mellitus is a major risk factor for cardiovascular disease and mortality. Uncontrolled type 2 diabetes mellitus results in a systemic milieu of increased circulating glucose and fatty acids. The development of insulin resistance in cardiac tissue decreases cellular glucose import and enhances mitochondrial fatty acid uptake. While triacylglycerol and cytotoxic lipid species begin to accumulate in the cardiomyocyte, the energy substrate utilization ratio of free fatty acids to glucose changes to almost entirely free fatty acids. Accumulating evidence suggests a role of miRNA in mediating this metabolic transition. Energy substrate metabolism, apoptosis, and the production and response to excess reactive oxygen species are regulated by miRNA expression. The current momentum for understanding the dynamics of miRNA expression is limited by a lack of understanding of how miRNA expression is controlled. While miRNAs are important regulators in both normal and pathological states, an additional layer of complexity is added when regulation of miRNA regulators is considered. miRNA expression is known to be regulated through a number of mechanisms, which include, but are not limited to, epigenetics, exosomal transport, processing, and posttranscriptional sequestration. The purpose of this review is to outline how mitochondrial processes are regulated by miRNAs in the diabetic heart. Furthermore, we will highlight the regulatory mechanisms, such as epigenetics, exosomal transport, miRNA processing, and posttranslational sequestration, that participate as regulators of miRNA expression. Additionally, current and future treatment strategies targeting dysfunctional mitochondrial processes in the diseased myocardium, as well as emerging miRNA-based therapies, will be summarized. PMID- 28986364 TI - Seropositivity combined with smoking is associated with increased prevalence of periodontitis in patients with rheumatoid arthritis. PMID- 28986370 TI - Gun injuries cost US nearly $3bn a year in hospital charges. PMID- 28986371 TI - Genotypic and Phenotypic Characteristics Associated with Biofilm Formation by Human Clinical Escherichia coli Isolates of Different Pathotypes. AB - Bacterial biofilm formation is a widespread phenomenon and a complex process requiring a set of genes facilitating the initial adhesion, maturation, and production of the extracellular polymeric matrix and subsequent dispersal of bacteria. Most studies on Escherichia coli biofilm formation have investigated nonpathogenic E. coli K-12 strains. Due to the extensive focus on laboratory strains in most studies, there is poor information regarding biofilm formation by pathogenic E. coli isolates. In this study, we genotypically and phenotypically characterized 187 human clinical E. coli isolates representing various pathotypes (e.g., uropathogenic, enteropathogenic, and enteroaggregative E. coli). We investigated the presence of biofilm-associated genes ("genotype") and phenotypically analyzed the isolates for motility and curli and cellulose production ("phenotype"). We developed a new screening method to examine the in vitro biofilm formation ability. In summary, we found a high prevalence of biofilm-associated genes. However, we could not detect a biofilm-associated gene or specific phenotype correlating with the biofilm formation ability. In contrast, we did identify an association of increased biofilm formation with a specific E. coli pathotype. Enteroaggregative E. coli (EAEC) was found to exhibit the highest capacity for biofilm formation. Using our image-based technology for the screening of biofilm formation, we demonstrated the characteristic biofilm formation pattern of EAEC, consisting of thick bacterial aggregates. In summary, our results highlight the fact that biofilm-promoting factors shown to be critical for biofilm formation in nonpathogenic strains do not reflect their impact in clinical isolates and that the ability of biofilm formation is a defined characteristic of EAEC.IMPORTANCE Bacterial biofilms are ubiquitous and consist of sessile bacterial cells surrounded by a self-produced extracellular polymeric matrix. They cause chronic and device-related infections due to their high resistance to antibiotics and the host immune system. In nonpathogenic Escherichia coli, cell surface components playing a pivotal role in biofilm formation are well known. In contrast, there is poor information for their role in biofilm formation of pathogenic isolates. Our study provides insights into the correlation of biofilm-associated genes or specific phenotypes with the biofilm formation ability of commensal and pathogenic E. coli Additionally, we describe a newly developed method enabling qualitative biofilm analysis by automated image analysis, which is beneficial for high-throughput screenings. Our results help to establish a better understanding of E. coli biofilm formation. PMID- 28986372 TI - Phylogenetic Backgrounds and Virulence-Associated Traits of Escherichia coli Isolates from Surface Waters and Diverse Animals in Minnesota and Wisconsin. AB - Possible external reservoirs for extraintestinal pathogenic Escherichia coli (ExPEC) strains that cause infections in humans are poorly defined. Because of the tremendous human health importance of ExPEC infections, we assessed surface waters and domesticated and wild animals in Minnesota and Wisconsin as potential reservoirs of ExPEC of human health relevance. We characterized 595 E. coli isolates (obtained from 1999 to 2002; 280 from seven surface water sites, 315 from feces of 13 wild and domesticated animal species) for phylogroup and virulence genotype, including inferred ExPEC status, by using multiplex PCR-based methods. We also compared the pulsed-field gel electrophoresis (PFGE) profiles of the isolates with a large private PFGE profile library. We found a predominance of non-ExPEC strains (95% and 93% among water and animal isolates, respectively), which were mainly from phylogroups A and B1, plus a minority of ExPEC strains (5% and 7% among water isolates and animal isolates, respectively), predominantly from phylogroup B2. The ExPEC strains, although significantly associated with cats, dogs, and turkeys, occurred in several additional animal species (goat, horse, chicken, pig) and were distributed broadly across all surface water sites. Virulence gene content among the animal source ExPEC isolates segregated significantly in relation to host species, following established patterns. PFGE analysis indicated that 11 study isolates closely matched (94% to 100% profile similarity) reference human clinical and fecal isolates. These findings imply what probably is a low but non-zero risk to humans from environmental and animal source E. coli isolates, especially those from specific human-associated animal species.IMPORTANCE Our detection of potentially pathogenic strains that may pose a health threat to humans among E. coli isolates from surface waters and wild and domesticated animals suggests a need for heightened attention to these reservoirs as possible sources for human acquisition of disease-causing E. coli Although cats, dogs, and turkeys were especially high-prevalence sources, the presence of such strains in other animal species and at all sampled water sites suggests that this potential risk may be widespread. PMID- 28986373 TI - Murein Hydrolase LytF of Streptococcus sanguinis and the Ecological Consequences of Competence Development. AB - The overall health of the oral cavity is dependent on proper homeostasis between health-associated bacterial colonizers and bacteria known to promote dental caries. Streptococcus sanguinis is a health-associated commensal organism, a known early colonizer of the acquired tooth pellicle, and is naturally competent. We have shown that LytF, a competence-controlled murein hydrolase, is capable of inducing the release of extracellular DNA (eDNA) from oral bacteria. Precipitated LytF and purified LytF were used as treatments against planktonic cultures and biofilms. Larger amounts of eDNA were released from cultures treated with protein samples containing LytF. Additionally, LytF could affect biofilm formation and cellular morphology. Biofilm formation was significantly decreased in the lytF complemented strain, in which increased amounts of LytF are present. The same strain also exhibited cell morphology defects in both planktonic cultures and biofilms. Furthermore, the LytF cell morphology phenotype was reproducible in wild-type cells using purified LytF protein. In sum, our findings demonstrate that LytF can induce the release of eDNA from oral bacteria, and they suggest that, without proper regulation of LytF, cells display morphological abnormalities that contribute to biofilm malformation. In the context of the oral biofilm, LytF may play important roles as part of the competence and biofilm development programs, as well as increasing the availability of eDNA.IMPORTANCEStreptococcus sanguinis, a commensal organism in the oral cavity and one of the pioneer colonizers of the tooth surface, is associated with the overall health of the oral environment. Our laboratory showed previously that, under aerobic conditions, S. sanguinis can produce H2O2 to inhibit the growth of bacterial species that promote dental caries. This production of H2O2 by S. sanguinis also induces the release of eDNA, which is essential for proper biofilm formation. Under anaerobic conditions, S. sanguinis does not produce H2O2 but DNA is still released. Determining how S. sanguinis releases DNA is thus essential to understand biofilm formation in the oral cavity. PMID- 28986374 TI - Chromosomal Aneuploidy Improves the Brewing Characteristics of Sake Yeast. AB - The effect of chromosomal aneuploidy on the brewing characteristics of brewery yeasts has not been studied. Here we report that chromosomal aneuploidy in sake brewery yeast (Saccharomyces cerevisiae) leads to the development of favorable brewing characteristics. We found that pyruvate-underproducing sake yeast, which produces less off-flavor diacetyl, is aneuploid and trisomic for chromosomes XI and XIV. To confirm that this phenotype is due to aneuploidy, we obtained 45 haploids with various chromosomal additions and investigated their brewing profiles. A greater number of chromosomes correlated with a decrease in pyruvate production. Especially, sake yeast haploids with extra chromosomes in addition to chromosome XI produced less pyruvate than euploids. Mitochondrion-related metabolites and intracellular oxygen species in chromosome XI aneuploids were higher than those in euploids, and this effect was canceled in their "petite" strains, suggesting that an increase in chromosomes upregulated mitochondrial activity and decreased pyruvate levels. These findings suggested that an increase in chromosome number, including chromosome XI, in sake yeast haploids leads to pyruvate underproduction through the augmentation of mitochondrial activity. This is the first report proposing that aneuploidy in brewery yeasts improves their brewing profile.IMPORTANCE Chromosomal aneuploidy has not been evaluated in development of sake brewing yeast strains. This study shows the relationship between chromosomal aneuploidy and brewing characteristics of brewery yeast strains. High concentrations of pyruvate during sake storage give rise to alpha acetolactate and, in turn, to high concentrations of diacetyl, which is considered an off-flavor. It was demonstrated that pyruvate-underproducing sake yeast is trisomic for chromosome XI and XIV. Furthermore, sake yeast haploids with extra chromosomes produced reduced levels of pyruvate and showed metabolic processes characteristic of increased mitochondrial activity. This novel discovery will enable the selection of favorable brewery yeasts by monitoring the copy numbers of specific chromosomes through a process that does not involve generation/use of genetically modified organisms. PMID- 28986375 TI - Stringent Response Regulators Contribute to the Recovery from Glucose-Phosphate Stress in Escherichia coli. AB - In enteric bacteria like Escherichia coli, the transcription factor SgrR and the small RNA SgrS regulate the response to glucose-phosphate stress, a metabolic dysfunction that results in growth inhibition and stems from the intracellular accumulation of sugar-phosphates. SgrR activates transcription of sgrS, and SgrS helps to rescue cells from stress in part by inhibiting uptake of stressor sugar phosphates. While the regulatory targets of this stress response are well described, less is known about how the SgrR-SgrS response itself is regulated. To further characterize regulation of the glucose-phosphate stress response, we screened global regulator gene mutants for growth changes during glucose phosphate stress. We found that deleting dksA, which encodes a regulator of the stringent response to nutrient starvation, decreases growth under glucose phosphate stress conditions. The stringent response alarmone regulator ppGpp (synthesized by RelA and SpoT) also contributes to recovery from glucose phosphate stress: as with dksA, mutating relA and spoT worsens the growth defect of an sgrS mutant during stress, although the sgrS relA spoT mutant defect was only detectable under lower stress levels. In addition, mutating dksA or relA and spoT lowers sgrS expression (as measured with a P sgrS-lacZ fusion), suggesting that the observed growth defects may be due to decreased induction of the glucose phosphate stress response or related targets. This regulatory effect could occur through altered sgrR transcription, as dksA and relA spoT mutants also exhibit decreased expression of a P sgrR-lacZ fusion. Taken together, this work supports a role for stringent response regulators in aiding the recovery from glucose phosphate stress.Importance Glucose-phosphate stress leads to growth inhibition in bacteria like Escherichia coli when certain sugar-phosphates accumulate in the cell. The transcription factor SgrR and the small RNA SgrS alleviate this stress, in part by preventing further sugar-phosphate transport. While the regulatory mechanisms of this response have been characterized, regulation of the SgrR-SgrS response itself is not as well understood. Here, we describe a role for stringent response regulators DksA and ppGpp in the response to glucose-phosphate stress. sgrS dksA and sgrS relA spoT mutants exhibit growth defects under glucose phosphate stress conditions. These defects may be due to a decrease in stress response induction, as deleting dksA or relA and spoT also results in decreased expression of sgrS and sgrR This research presents one of the first regulatory effects on the glucose-phosphate stress response outside of SgrR and SgrS and depicts a novel connection between these two metabolic stress responses. PMID- 28986376 TI - Differential MS2 Interaction with Food Contact Surfaces Determined by Atomic Force Microscopy and Virus Recovery. AB - Enteric viruses are recognized as major etiologies of U.S. foodborne infections. These viruses are easily transmitted via food contact surfaces. Understanding virus interactions with surfaces may facilitate the development of improved means for their removal, thus reducing transmission. Using MS2 coliphage as a virus surrogate, the strength of virus adhesion to common food processing and preparation surfaces of polyvinyl chloride (PVC) and glass was assessed by atomic force microscopy (AFM) and virus recovery assays. The interaction forces of MS2 with various surfaces were measured from adhesion peaks in force-distance curves registered using a spherical bead probe preconjugated with MS2 particles. MS2 in phosphate-buffered saline (PBS) demonstrated approximately 5 times less adhesion force to glass (0.54 nN) than to PVC (2.87 nN) (P < 0.0001). This was consistent with the virus recovery data, which showed 1.4-fold fewer virus PFU recovered from PVC than from glass after identical inoculations and 24 h of cold storage. The difference in adhesion was ascribed to both intrinsic chemical characteristics and the substrate surface porosity (smooth glass versus porous PVC). Incorporating a surfactant micellar solution of sodium dodecyl sulfate (SDS) into the PBS reduced the adhesion force for PVC (~0 nN) and consistently increased virus recovery by 19%. With direct and indirect evidence of virus adhesion, this study illustrated a two-way assessment of virus adhesion for the initial evaluation of potential means to mitigate virus adhesion to food contact surfaces.IMPORTANCE The spread of foodborne viruses is likely associated with their adhesive nature. Virus attachment on food contact surfaces has been evaluated by quantitating virus recoveries from inoculated surfaces. This study aimed to evaluate the microenvironment in which nanometer-sized viruses interact with food contact surfaces and to compare the virus adhesion differences using AFM. The virus surrogate MS2 demonstrated less adhesion force to glass than to PVC via AFM, with the force-contributing factors including the intrinsic nature and the topography of the contact surfaces. This adhesion finding is consistent with the virus recoveries, which were determined indirectly. Greater numbers of viruses were recovered from glass than from PVC, after application at the same levels. The stronger MS2 adhesion onto PVC could be interrupted by incorporating a surfactant during the interaction between the virus and the contact surface. This study increases our understanding of the virus adhesion microenvironment and indicates ways to mitigate virus adhesion onto contact surfaces. PMID- 28986377 TI - Stenotrophomonas-Like Bacteria Are Widespread Symbionts in Cone Snail Venom Ducts. AB - Cone snails are biomedically important sources of peptide drugs, but it is not known whether snail-associated bacteria affect venom chemistry. To begin to answer this question, we performed 16S rRNA gene amplicon sequencing of eight cone snail species, comparing their microbiomes with each other and with those from a variety of other marine invertebrates. We show that the cone snail microbiome is distinct from those in other marine invertebrates and conserved in specimens from around the world, including the Philippines, Guam, California, and Florida. We found that all venom ducts examined contain diverse 16S rRNA gene sequences bearing closest similarity to Stenotrophomonas bacteria. These sequences represent specific symbionts that live in the lumen of the venom duct, where bioactive venom peptides are synthesized.IMPORTANCE In animals, symbiotic bacteria contribute critically to metabolism. Cone snails are renowned for the production of venoms that are used as medicines and as probes for biological study. In principle, symbiotic bacterial metabolism could either degrade or synthesize active venom components, and previous publications show that bacteria do indeed contribute small molecules to some venoms. Therefore, understanding symbiosis in cone snails will contribute to further drug discovery efforts. Here, we describe an unexpected, specific symbiosis between bacteria and cone snails from around the world. PMID- 28986378 TI - Use of Endophytic and Rhizosphere Actinobacteria from Grapevine Plants To Reduce Nursery Fungal Graft Infections That Lead to Young Grapevine Decline. AB - Endophytic and rhizosphere actinobacteria isolated from the root system of 1-year old grafted Vitis vinifera plants were evaluated for their activities against fungi that cause grapevine trunk diseases. A total of 58 endophytic and 94 rhizosphere isolates were tested. Based on an in vitro bioassay, 15.5% of the endophytic isolates and 30.8% of the rhizosphere isolates exhibited antifungal activity against the fungal pathogen Diplodia seriata, whereas 13.8% of the endophytic isolates and 16.0% of the rhizosphere isolates showed antifungal activity against Dactylonectria macrodidyma (formerly Ilyonectria macrodidyma). The strains which showed the greatest in vitro efficacy against both pathogens were further analyzed for their ability to inhibit the growth of Phaeomoniella chlamydospora and Phaeoacremonium minimum (formerly Phaeoacremonium aleophilum). Based on their antifungal activity, three rhizosphere isolates and three endophytic isolates were applied on grafts in an open-root field nursery in a 3 year trial. The field trial led to the identification of one endophytic strain, Streptomyces sp. VV/E1, and two rhizosphere isolates, Streptomyces sp. VV/R1 and Streptomyces sp. VV/R4, which significantly reduced the infection rates produced by the fungal pathogens Dactylonectria sp., Ilyonectria sp., P. chlamydospora, and P. minimum, all of which cause young grapevine decline. The VV/R1 and VV/R4 isolates also significantly reduced the mortality level of grafted plants in the nursery. This study shows that certain actinobacteria could represent a promising new tool for controlling fungal trunk pathogens that infect grapevine plants through the root system in nurseries.IMPORTANCE Grapevine trunk diseases are a major threat to the wine and grape industry worldwide. They cause a significant reduction in yields as well as in grape quality, and they can even cause plant death. Trunk diseases are caused by fungal pathogens that enter through pruning wounds and/or the root system. Although different strategies have recently been developed to protect pruning wounds using antifungal compounds (natural or synthetic) or biocontrol agents, no tools are yet available for controlling soil pathogens that infect plants through their root system. This study shows that different actinobacterial isolates, when applied to grafts in a nursery, can significantly reduce the infection rate caused by fungal pathogens that enter through the root system. This is a new, promising, and green alternative for preventing the decline of young grapevines in nurseries and vineyards. PMID- 28986379 TI - Functional analysis of the Glucan Degradation Locus (GDL) in Caldicellulosiruptor bescii reveals essential roles of component glycoside hydrolases in plant biomass deconstruction. AB - The ability to hydrolyze microcrystalline cellulose is an uncommon feature in the microbial world, but one that can be exploited for conversion of lignocellulosic feedstocks into bio-based fuels and chemicals. Understanding the physiological and biochemical mechanisms by which microorganisms deconstruct cellulosic material is key to achieving this objective. The Glucan Degradation Locus (GDL) in the genomes of extremely thermophilic Caldicellulosiruptor species encodes polysaccharide lyases (PLs), unique cellulose binding proteins (tapirins), and putative post-translational modifying enzymes, in addition to multi-domain, multi functional glycoside hydrolases (GHs), thereby representing an alternative paradigm for plant biomass degradation, as compared to fungal or cellulosomal systems. To examine the individual and collective in vivo roles of the glycolytic enzymes, the six GHs in the GDL of Caldicellulosiruptor bescii were systematically deleted, and the extent to which the resulting mutant strains could solubilize microcrystalline cellulose (Avicel) and plant biomasses (switchgrass or poplar) was examined. Three of the GDL enzymes, Athe_1867 (CelA) (GH9-CBM3-CBM3-CBM3-GH48), Athe_1859 (GH5-CBM3-CBM3-GH44), and Athe_1857 (GH10 CBM3-CBM3-GH48), acted synergistically in vivo and accounted for 92% of naked microcellulose (Avicel) degradation. However, the relative importance of the GDL GHs varied for the plant biomass substrates tested. Furthermore, mixed cultures of mutant strains showed switchgrass solubilization depended on the secretome bound enzymes collectively produced by the culture and not on the specific strain from which they came. These results demonstrate that certain GDL GHs are primarily responsible for the degradation of microcrystalline-containing substrates by C. bescii and provide new insights into the workings of a novel microbial mechanism for lignocellulose utilization.Importance The efficient and extensive degradation of complex polysaccharides in lignocellulosic biomass, particularly microcrystalline cellulose, remains a major barrier to its use as a renewable feedstock for the production of fuels and chemicals. Extremely thermophilic bacteria from the genus Caldicellulosiruptor rapidly degrade plant biomass to fermentable sugars at temperatures between 70-78 degrees C, although the specific mechanism by which this occurs is not clear. Previous comparative genomic studies identified a genomic locus found only in certain Caldicellulosiruptor species that was hypothesized to be mainly responsible for microcrystalline cellulose degradation. By systematically deleting genes in this locus in Caldicellulosiruptor bescii, the nuanced, substrate-specific, in vivo roles of glycolytic enzymes in deconstructing crystalline cellulose and plant biomasses could be discerned. The results here point to synergism of three multi domain cellulases in C. bescii, working in conjunction with the aggregate, secreted enzyme inventory, as the key to the plant biomass degradation ability by this extreme thermophile. PMID- 28986380 TI - Astrocytes Promote Medulloblastoma Progression through Hedgehog Secretion. AB - Astrocytes, the most abundant type of glial cells in the brain, play critical roles in supporting neuronal development and brain function. Although astrocytes have been frequently detected in brain tumors, including medulloblastoma (MB), their functions in tumorigenesis are not clear. Here, we demonstrate that astrocytes are essential components of the MB tumor microenvironment. Tumor associated astrocytes (TAA) secrete the ligand sonic hedgehog (Shh), which is required for maintaining MB cell proliferation despite the absence of its primary receptor Patched-1 (Ptch1). Shh drives expression of Nestin in MB cells through a smoothened-dependent, but Gli1-independent mechanism. Ablation of TAA dramatically suppresses Nestin expression and blocks tumor growth. These findings demonstrate an indispensable role for astrocytes in MB tumorigenesis and reveal a novel Ptch1-independent Shh pathway involved in MB progression. Cancer Res; 77(23); 6692-703. (c)2017 AACR. PMID- 28986381 TI - Chemotherapeutic Dose Scheduling Based on Tumor Growth Rates Provides a Case for Low-Dose Metronomic High-Entropy Therapies. AB - We extended the classical tumor regression models such as Skipper's laws and the Norton-Simon hypothesis from instantaneous regression rates to the cumulative effect over repeated cycles of chemotherapy. To achieve this end, we used a stochastic Moran process model of tumor cell kinetics coupled with a prisoner's dilemma game-theoretic cell-cell interaction model to design chemotherapeutic strategies tailored to different tumor growth characteristics. Using the Shannon entropy as a novel tool to quantify the success of dosing strategies, we contrasted MTD strategies as compared with low-dose, high-density metronomic strategies (LDM) for tumors with different growth rates. Our results show that LDM strategies outperformed MTD strategies in total tumor cell reduction. This advantage was magnified for fast-growing tumors that thrive on long periods of unhindered growth without chemotherapy drugs present and was not evident after a single cycle of chemotherapy but grew after each subsequent cycle of repeated chemotherapy. The evolutionary growth/regression model introduced in this article agrees well with murine models. Overall, this model supports the concept of designing different chemotherapeutic schedules for tumors with different growth rates and develops quantitative tools to optimize these schedules for maintaining low-volume tumors. Cancer Res; 77(23); 6717-28. (c)2017 AACR. PMID- 28986384 TI - Mass spectrometry for fragment screening. AB - Fragment-based approaches in chemical biology and drug discovery have been widely adopted worldwide in both academia and industry. Fragment hits tend to interact weakly with their targets, necessitating the use of sensitive biophysical techniques to detect their binding. Common fragment screening techniques include differential scanning fluorimetry (DSF) and ligand-observed NMR. Validation and characterization of hits is usually performed using a combination of protein observed NMR, isothermal titration calorimetry (ITC) and X-ray crystallography. In this context, MS is a relatively underutilized technique in fragment screening for drug discovery. MS-based techniques have the advantage of high sensitivity, low sample consumption and being label-free. This review highlights recent examples of the emerging use of MS-based techniques in fragment screening. PMID- 28986383 TI - Copper Chelation Inhibits BRAFV600E-Driven Melanomagenesis and Counters Resistance to BRAFV600E and MEK1/2 Inhibitors. AB - MEK1/2 and BRAFV600E inhibitors are used to treat BRAFV600E-positive melanoma, with other cancers under evaluation. Genetic perturbation of copper import or pharmacologic reduction of copper with the clinical copper chelator TTM inhibits MEK1/2 kinase activity and reduces BRAFV600E-driven tumorigenesis. In this study, we report that TTM inhibited transformed growth of melanoma cell lines resistant to BRAF or MEK1/2 inhibitors and enhanced the antineoplastic activity of these inhibitors. TTM also provided a survival advantage in a genetically engineered mouse model of melanoma, and when accounting for putative overdosing, trended toward an increase in the survival benefit afforded by BRAF inhibition. This effect was phenocopied by genetically inhibiting copper import in tumors, which was linked to a reduction in MAPK signaling. Thus, TTM reduces copper levels and MAPK signaling, thereby inhibiting BRAFV600E-driven melanoma tumor growth. These observations inform and support clinical evaluation of TTM in melanoma. Cancer Res; 77(22); 6240-52. (c)2017 AACR. PMID- 28986382 TI - Loss of FOXO1 Cooperates with TMPRSS2-ERG Overexpression to Promote Prostate Tumorigenesis and Cell Invasion. AB - E26 transformation-specific transcription factor ERG is aberrantly overexpressed in approximately 50% of all human prostate cancer due to TMPRSS2-ERG gene rearrangements. However, mice with prostate-specific transgenic expression of prostate cancer-associated ERG alone fail to develop prostate cancer, highlighting that ERG requires other lesions to drive prostate tumorigenesis. Forkhead box (FOXO) transcription factor FOXO1 is a tumor suppressor that is frequently inactivated in human prostate cancer. Here, we demonstrate that FOXO1, but not other FOXO proteins (FOXO3 and FOXO4), binds and inhibits the transcriptional activity of prostate cancer-associated ERG independently of FOXO1 transcriptional activity. Knockdown of endogenous FOXO1 increased invasion of TMPRSS2-ERG fusion-positive VCaP cells, an effect completely abolished by ERG knockdown. Patient specimen analysis demonstrated that FOXO1 and ERG protein expression inversely correlated in a subset of human prostate cancer. Although human ERG transgene expression or homozygous deletion of Foxo1 alone in the mouse prostate failed to promote tumorigenesis, concomitant ERG transgene expression and Foxo1 deletion resulted in upregulation of ERG target genes, increased cell proliferation, and formation of high-grade prostatic intraepithelial neoplasia. Overall, we provide biochemical and genetic evidence that aberrantly activated ERG cooperates with FOXO1 deficiency to promote prostate tumorigenesis and cell invasion. Our findings enhance understanding of prostate cancer etiology and suggest that the FOXO1-ERG signaling axis can be a potential target for treatment of prostate cancer. Cancer Res; 77(23); 6524-37. (c)2017 AACR. PMID- 28986386 TI - Bacterial isolates and antimicrobial susceptibilities from odontogenic abscesses in rabbits: 48 cases. AB - The medical record database of a veterinary teaching hospital was searched from 2000 through 2014 for records of client-owned rabbits with positive cultures from odontogenic abscesses. Data reviewed included sex, age, abscess location, sampling technique, previous antimicrobial treatments, microorganisms identified and antibiotic susceptibility of aerobic bacteria. Forty-eight client owned rabbits with one or more odontogenic abscesses and culture results were evaluated. One hundred and eighty-five isolates (52 aerobic, 133 anaerobic) were identified from 61 positive cultures from odontogenic abscesses. The most common aerobic bacterial isolates were Pseudomonas aeruginosa (14/52), Pasteurella species (10/52), Streptococcus species (8/52) and Staphylococcus species (7/52). The most common anaerobic bacterial isolates were Fusobacterium species (36/133), Peptostreptococcus species (27/133) and Bacteroides species (27/133). Mixed aerobic and anaerobic isolates were detected in 73.3 per cent of cultures and 50.8 per cent of the samples had greater than three isolates. P aeruginosa was susceptible to amikacin and gentamicin, had variable resistance to enrofloxacin, and resistance to chloramphenicol. Pasteurella species, Streptococcus species and Staphylococcus species isolates were susceptible to most antibiotics tested. The bacterial isolates from rabbit odontogenic abscesses are a mixture of aerobic and anaerobic Gram-positive and Gram-negative organisms and without culture and susceptibility testing, it is difficult to predict appropriate antimicrobial treatment. PMID- 28986385 TI - The role of halofuginone in fibrosis: more to be explored? AB - Fibrosis, which can be defined as an abnormal or excessive accumulation of extracellular matrix (ECM), particularly fibrillar collagens, is a key driver of progressive organ dysfunction in many inflammatory and metabolic diseases, including idiopathic pulmonary fibrosis (IPF), cirrhosis, nephropathy, and oral submucous fibrosis (OSF). It has been estimated to contribute to ~45% of deaths in the developed world. Therefore, agents that target specific fibrotic pathways, with the consequence of slowing, arresting, or even reversing the progression of tissue fibrogenesis, are urgently needed. 7-Bromo-6-chloro-3-[3-(3-hydroxy-2 piperidinyl)-2-oxopropyl]-4(3H)-quinazolinone (halofuginone), an analog of febrifugine, which specifically targets the pathogenesis of ECM proteins, inhibits tissue fibrosis and regeneration and even affects the development of tumors in various tissues. Four modes of actions of halofuginone against fibrosis have been presented: 1) Inhibition of mothers against decapentaplegic homolog 3 (Smad3) phosphorylation downstream of the TGF-beta signaling pathway, 2) reduction of collagen amounts, 3) decreases in ECM protein, and 4) selective prevention of Th17 cell differentiation. In this review, we will mainly focus on the rationale for halofuginone against fibrosis. PMID- 28986387 TI - Determination of reference values for intraocular pressure and Schirmer tear test results in clinically normal domestic donkeys (Equus asinus). AB - This study was conducted to establish normal reference range for the Schirmer tear test (STT) and intraocular pressure (IOP) in clinically normal donkeys for use in clinical practice. Sixteen adult Ethiopian domestic donkeys were used in this study. Complete ophthalmic examinations were performed without chemical restraint. STT values were evaluated in both eyes of all donkeys using a commercial STT strip. IOP was measured in both eyes with a Tono-Pen Vet (Reichert. USA) without using regional nerve blocks. STT values for all eyes (n=32) were 22.1+/-6.9 mm/minute with a range of 13-35 mm/minute. Comparison of mean STT values between right (n=16) and left eyes (n=16) showed no differences (P=0.6). Mean +/-sd IOP values by applanation tonometry were 17.8+/-3.7 mmHg (range 13.5-24.5 mmHg). Comparison of mean IOP values between right (n=16) and left eyes (n=16) showed no differences (P=0.7). This initial survey provides means and ranges for IOP and STT values in donkeys. These data will assist veterinary ophthalmologists in more accurate diagnosis and management of ophthalmic diseases in donkeys, including keratoconjunctivitis sicca and glaucoma. PMID- 28986388 TI - Shocking the system: AEDs in military resuscitation. AB - Automated external defibrillator (AED) devices have been in routine clinical use since the early 1990s to deliver life-saving shocks to appropriate patients in non-clinical environments. As expectations of survival from out-of-hospital cardiac arrest increase, and evidence incontrovertibly points to reduced timelines as the most crucial factor in achieving return of spontaneous circulation, questions regarding the availability and location of AEDs in the UK military need to be readdressed. This article explores the background of AEDs and reviews their history, life-saving potential and defines current and best practice. It goes on to review the evidence surrounding training and looks to identify knowledge gaps that might be addressed effectively by future research. Finally, it makes recommendations regarding training, availability of AEDs on military bases and locations most likely to deliver good outcomes for military personnel in the future. PMID- 28986389 TI - Is there a need for a postgraduate military healthcare qualification? PMID- 28986390 TI - Relationship between 1.5-mile run time, injury risk and training outcome in British Army recruits. AB - BACKGROUND: 1.5-mile run time, as a surrogate measure of aerobic fitness, is associated with musculoskeletal injury (MSI) risk in military recruits. This study aimed to determine if 1.5-mile run times can predict injury risk and attrition rates from phase 1 (initial) training and determine if a link exists between phase 1 and 2 discharge outcomes in British Army recruits. METHOD: 1.5 mile times from week 1 of initial training and MSI reported during training were retrieved for 3446 male recruits. Run times were examined against injury occurrence and training outcomes for 3050 recruits, using a Binary Logistic Regression and chi2 analysis. RESULTS: The 1.5-mile run can predict injury risk and phase 1 attrition rates (chi2(1)=59.3 p<0.001, chi2(1)=66.873 p<0.001). Slower 1.5-mile run times were associated with higher injury occurrence (chi2(1)=59.3 p<0.001) and reduced phase 1 (chi2 104.609a p<0.001) and 2 (chi2 84.978a p<0.001) success. CONCLUSION: The 1.5-mile run can be used to guide a future standard that will in turn help reduce injury occurrence and improve training success. PMID- 28986392 TI - Clipping Chlamy Genes: Improved Methods for Targeted Gene Editing in Chlamydomonas. PMID- 28986393 TI - Making Connections: MAC Function in Splicing and MicroRNA Biogenesis. PMID- 28986391 TI - Altered hydroxymethylation is seen at regulatory regions in pancreatic cancer and regulates oncogenic pathways. AB - Transcriptional deregulation of oncogenic pathways is a hallmark of cancer and can be due to epigenetic alterations. 5-Hydroxymethylcytosine (5-hmC) is an epigenetic modification that has not been studied in pancreatic cancer. Genome wide analysis of 5-hmC-enriched loci with hmC-seal was conducted in a cohort of low-passage pancreatic cancer cell lines, primary patient-derived xenografts, and pancreatic controls and revealed strikingly altered patterns in neoplastic tissues. Differentially hydroxymethylated regions preferentially affected known regulatory regions of the genome, specifically overlapping with known H3K4me1 enhancers. Furthermore, base pair resolution analysis of cytosine methylation and hydroxymethylation with oxidative bisulfite sequencing was conducted and correlated with chromatin accessibility by ATAC-seq and gene expression by RNA seq in pancreatic cancer and control samples. 5-hmC was specifically enriched at open regions of chromatin, and gain of 5-hmC was correlated with up-regulation of the cognate transcripts, including many oncogenic pathways implicated in pancreatic neoplasia, such as MYC, KRAS, VEGFA, and BRD4 Specifically, BRD4 was overexpressed and acquired 5-hmC at enhancer regions in the majority of neoplastic samples. Functionally, acquisition of 5-hmC at BRD4 promoter was associated with increase in transcript expression in reporter assays and primary samples. Furthermore, blockade of BRD4 inhibited pancreatic cancer growth in vivo. In summary, redistribution of 5-hmC and preferential enrichment at oncogenic enhancers is a novel regulatory mechanism in human pancreatic cancer. PMID- 28986394 TI - Man with advanced MND loses challenge for an assisted death. PMID- 28986395 TI - NHS plays second fiddle to Brexit as prime minister struggles to find voice. PMID- 28986396 TI - ACE-modulated adiposity is related to higher energy expenditure and independent of lipolysis and glucose incorporation into lipids in adipocytes. AB - Emerging evidence suggests that both systemic and white adipose tissue-renin angiotensin system components influence body weight control. We previously demonstrated that higher angiotensin-converting enzyme (ACE) gene expression is associated with lower body adiposity in a rodent model. In this study, we tested the hypothesis that a higher ACE gene dosage reduces fat accumulation by increasing energy expenditure and modulating lipolysis and glucose incorporation into lipids in adipocytes. After a 12 wk follow-up period, transgenic mice harboring three ACE (3ACE) gene copies displayed diminished WAT mass, lipid content in their carcasses, adipocyte hypotrophy, and higher resting oxygen uptake (Vo2) in comparison with animals with one ACE gene copy (1ACE) after long fasting (12 h). No differences were found in food intake and in the rates of lipolysis and glucose incorporation into lipids in adipocytes. To assess whether this response involves increased angiotensin II type I receptor (AT1R) activation, AT1R blocker (losartan) was used in a separate group of 3ACE mice with body weight and adiposity comparable to that in the other 3ACE animals. We suggest that fasting-induced lower adiposity observed in animals with 3ACE gene copies might be associated with a higher expense of energy reserves; this response did not involve AT1R activation. PMID- 28986398 TI - Inhibition of Cdk5 Promotes beta-Cell Differentiation From Ductal Progenitors. AB - Inhibition of notch signaling is known to induce differentiation of endocrine cells in zebrafish and mouse. After performing an unbiased in vivo screen of ~2,200 small molecules in zebrafish, we identified an inhibitor of Cdk5 (roscovitine), which potentiated the formation of beta-cells along the intrapancreatic duct during concurrent inhibition of notch signaling. We confirmed and characterized the effect with a more selective Cdk5 inhibitor, (R) DRF053, which specifically increased the number of duct-derived beta-cells without affecting their proliferation. By duct-specific overexpression of the endogenous Cdk5 inhibitors Cdk5rap1 or Cdkal1 (which previously have been linked to diabetes in genome-wide association studies), as well as deleting cdk5, we validated the role of chemical Cdk5 inhibition in beta-cell differentiation by genetic means. Moreover, the cdk5 mutant zebrafish displayed an increased number of beta-cells independently of inhibition of notch signaling, in both the basal state and during beta-cell regeneration. Importantly, the effect of Cdk5 inhibition to promote beta-cell formation was conserved in mouse embryonic pancreatic explants, adult mice with pancreatic ductal ligation injury, and human induced pluripotent stem (iPS) cells. Thus, we have revealed a previously unknown role of Cdk5 as an endogenous suppressor of beta-cell differentiation and thereby further highlighted its importance in diabetes. PMID- 28986397 TI - Potential mechanisms of hypothalamic renin-angiotensin system activation by leptin and DOCA-salt for the control of resting metabolism. AB - The renin-angiotensin system (RAS), originally described as a circulating hormone system, is an enzymatic cascade in which the final vasoactive peptide angiotensin II (ANG) regulates cardiovascular, hydromineral, and metabolic functions. The RAS is also synthesized locally in a number of tissues including the brain, where it can act in a paracrine fashion to regulate blood pressure, thirst, fluid balance, and resting energy expenditure/resting metabolic rate (RMR). Recent studies demonstrate that ANG AT1A receptors (Agtr1a) specifically in agouti-related peptide (AgRP) neurons of the arcuate nucleus (ARC) coordinate autonomic and energy expenditure responses to various stimuli including deoxycorticosterone acetate (DOCA)-salt, high-fat feeding, and leptin. It remains unclear, however, how these disparate stimuli converge upon and activate this specific population of AT1A receptors in AgRP neurons. We hypothesize that these stimuli may act to stimulate local expression of the angiotensinogen (AGT) precursor for ANG, or the expression of AT1A receptors, and thereby local activity of the RAS within the (ARC). Here we review mechanisms that may control AGT and AT1A expression within the central nervous system, with a particular focus on mechanisms activated by steroids, dietary fat, and leptin. PMID- 28986399 TI - Objectively Measured Physical Activity, Sedentary Behavior, and Genetic Predisposition to Obesity in U.S. Hispanics/Latinos: Results From the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). AB - Studies using self-reported data suggest a gene-physical activity interaction on obesity, yet the influence of sedentary behavior, distinct from a lack of physical activity, on genetic associations with obesity remains unclear. We analyzed interactions of accelerometer-measured moderate to vigorous physical activity (MVPA) and time spent sedentary with genetic variants on obesity among 9,645 U.S. Hispanics/Latinos. An overall genetic risk score (GRS), a central nervous system (CNS)-related GRS, and a non-CNS-related GRS were calculated based on 97 BMI-associated single nucleotide polymorphisms (SNPs). Genetic association with BMI was stronger in individuals with lower MVPA (first tertile) versus higher MVPA (third tertile) (beta = 0.78 kg/m2 [SE, 0.10 kg/m2] vs. 0.39 kg/m2 [0.09 kg/m2] per SD increment of GRS; Pinteraction = 0.005), and in those with more time spent sedentary (third tertile) versus less time spent sedentary (first tertile) (beta = 0.73 kg/m2 [SE, 0.10 kg/m2] vs. 0.44 kg/m2 [0.09 kg/m2]; Pinteraction = 0.006). Similar significant interaction patterns were observed for obesity risk, body fat mass, fat percentage, fat mass index, and waist circumference, but not for fat-free mass. The CNS-related GRS, but not the non CNS-related GRS, showed significant interactions with MVPA and sedentary behavior, with effects on BMI and other adiposity traits. Our data suggest that both increasing physical activity and reducing sedentary behavior may attenuate genetic associations with obesity, although the independence of these interaction effects needs to be investigated further. PMID- 28986400 TI - Preoperative selective vs non-selective alpha-blockade in PPGL patients undergoing adrenalectomy. AB - PURPOSE: Preoperative preparation for adrenalectomy for pheochromocytomas and paragangliomas (PPGL) is universally recognized as necessary, while the optimal strategy remains controversial. Our aims were to increase intraoperative hemodynamic stability, expedite postoperative recovery, decrease side effects and reduce costs for patients with PPGL undergoing adrenalectomy. METHODS: We identified 526 patients undergoing open adrenalectomy for PPGL in the West China Hospital of Sichuan University between May, 2007 and December, 2016. 149 patients received preoperative selective alpha-blockade with phenoxybenzamine, and 377 patients received non-selective alpha-blockade with prazosin, doxazosin or terazosin. There were no statistical differences between groups regarding preoperative patient and tumor characteristics. Operations were planned once hypertensive patients were well-controlled with blood pressure <=130/85 mmHg. Intraoperatively, all patients received arterial blood pressure monitoring, and indwelling urinary catheters to record urine output. We recorded intraoperative hemodynamics, status in the postanesthesia or intensive care unit, postoperative recovery and complications. RESULTS: Patients in the non-selective group showed a more significant decline in postoperative systolic blood pressure than the selective group (P = 0.041). Also, patients in the non-selective group appeared to receive a long-term anti-hypertensive effect, especially for diastolic blood pressure (P = 0.037), which was a novel finding, based on the current literature. CONCLUSIONS: Our results confirmed that non-selective alpha-blockade produced a more significant anti-hypertensive effect than selective alpha-blockade. However, we found no significant difference in intraoperative hemodynamic instability, postoperative recovery and postoperative complications between groups. PMID- 28986401 TI - Activation of CD4+ and CD8+ T-lymphocytes by insulin and GAD in patients with type 1 or 2 diabetes mellitus. AB - BACKGROUND: The origin of autoimmune disease type 1 diabetes is still unknown. AIM: This study assessed the activation of CD4+ and CD8+ T-lymphocytes by human insulin and human glutamate decarboxylase (GAD) in patients with type 1 or type 2 diabetes mellitus (DM) and healthy volunteers. MATERIALS AND METHODS: The expression of CD69, a marker of T-lymphocyte activity, was determined in whole blood samples by flow cytometry after 12 h of incubation with or without insulin or GAD. The analysis included samples from 12 type 1 DM patients, 14 type 2 DM patients and 12 healthy volunteers. RESULTS: Significant increases in the number of activated CD4+ and CD8+ T-lymphocytes following pre-incubation of whole blood samples with human insulin or GAD were observed in samples from patients with type 1 DM, whereas no activation of these cells was detected in samples from either type 2 DM patients or healthy subjects. DISCUSSION: These results indicated that latent pre-activation of CD4+ and CD8+ T-lymphocytes in response to insulin or GAD epitopes occurred in type 1 DM patients. CONCLUSION: These findings suggest that pre-immunization against insulin and/or GAD might be associated with the development of type 1 DM. Alternatively, these results might reflect a non-specific, bystander autoimmune response. PMID- 28986403 TI - Dutch geriatrician faces charges over euthanasia case. PMID- 28986404 TI - Predictors of successful chronic total occlusion percutaneous coronary interventions: a systematic review and meta-analysis. AB - OBJECTIVE: The aim of this study was to identify positive and negative predictors of technical and clinical success for percutaneous coronary intervention (PCI) of chronic total occlusions (CTO). METHODS: We conducted a systematic review and meta-analysis of studies published between 2000 and 2016 analysing rates of CTO PCI success with respect to demographic and angiographic characteristics. Crude ORs and 95% CIs for each predictor were calculated using a random effects model. Predictors of technical and clinical success were assessed among 28 demographic and 31 angiographic variables. Clinical success was defined as technical success without major adverse cardiac events. RESULTS: A total of 61 studies, totalling 69 886 patients were included in this analysis. The major demographic characteristics associated with a 20% or greater reduction in the odds of technical and clinical success were a history of myocardial infarction, PCI, coronary artery bypass grafting, stroke/transient ischaemic attack and peripheral vascular disease. Angiographic factors were generally stronger predictors of reduced technical and clinical success. Those associated with >20% odds reduction included non-left anterior descending CTOs, multivessel disease, presence of bridging collaterals, moderate-to-severe calcification, >45 degree vessel bending, tortuous vessel, blunt stump and ostial lesions. Of these, novel predictors included prior PCI, prior stroke, peripheral vascular disease, presence of multivessel disease and bridging collaterals. CONCLUSION: The present study has identified strong negative predictors for clinical success for CTO PCI, which will aid in patient selection for this procedure. PMID- 28986402 TI - MicroRNA expression profiles and type 1 diabetes mellitus: systematic review and bioinformatic analysis. AB - Growing evidence indicates that microRNAs (miRNAs) have a key role in processes involved in type 1 diabetes mellitus (T1DM) pathogenesis, including immune system functions and beta-cell metabolism and death. Although dysregulated miRNA profiles have been identified in T1DM patients, results are inconclusive; with only few miRNAs being consistently dysregulated among studies. Thus, we performed a systematic review of the literature on the subject, followed by bioinformatic analysis, to point out which miRNAs are dysregulated in T1DM-related tissues and in which pathways they act. PubMed and EMBASE were searched to identify all studies that compared miRNA expressions between T1DM patients and non-diabetic controls. Search was completed in August, 2017. Those miRNAs consistently dysregulated in T1DM-related tissues were submitted to bioinformatic analysis, using six databases of miRNA-target gene interactions to retrieve their putative targets and identify potentially affected pathways under their regulation. Thirty three studies were included in the systematic review: 19 of them reported miRNA expressions in human samples, 13 in murine models and one in both human and murine samples. Among 278 dysregulated miRNAs reported in these studies, 25.9% were reported in at least 2 studies; however, only 48 of them were analyzed in tissues directly related to T1DM pathogenesis (serum/plasma, pancreas and peripheral blood mononuclear cells (PBMCs)). Regarding circulating miRNAs, 11 were consistently dysregulated in T1DM patients compared to controls: miR-21-5p, miR-24-3p, miR-100-5p, miR-146a-5p, miR-148a-3p, miR-150-5p, miR-181a-5p, miR-210 5p, miR-342-3p, miR-375 and miR-1275. The bioinformatic analysis retrieved a total of 5867 validated and 2979 predicted miRNA-target interactions for human miRNAs. In functional enrichment analysis of miRNA target genes, 77 KEGG terms were enriched for more than one miRNA. These miRNAs are involved in pathways related to immune system function, cell survival, cell proliferation and insulin biosynthesis and secretion. In conclusion, eleven circulating miRNAs seem to be dysregulated in T1DM patients in different studies, being potential circulating biomarkers of this disease. PMID- 28986405 TI - Renin-angiotensin system blockade therapy after transcatheter aortic valve implantation. AB - OBJECTIVE: The persistence of left ventricular (LV) hypertrophy is associated with poor clinical outcomes after transcatheter aortic valve implantation (TAVI) for aortic stenosis. However, the optimal medical therapy after TAVI remains unknown. We investigated the effect of renin-angiotensin system (RAS) blockade therapy on LV hypertrophy and mortality in patients undergoing TAVI. METHODS: Between October 2013 and April 2016, 1215 patients undergoing TAVI were prospectively enrolled in the Optimized CathEter vAlvular iNtervention (OCEAN) TAVI registry. This cohort was stratified according to the postoperative usage of RAS blockade therapy with angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs). Patients with at least two prescriptions dispensed 180 days apart after TAVI and at least a 6-month follow-up constituted the RAS blockade group (n=371), while those not prescribed any ACE inhibitors or ARBs after TAVI were included in the no RAS blockade group (n=189). RESULTS: At 6 months postoperatively, the RAS blockade group had significantly greater LV mass index regression than the no RAS blockade group (-9+/-24% vs -2+/-25%, p=0.024). Kaplan-Meier analysis revealed a significantly lower cumulative 2-year mortality in the RAS blockade than that in the no RAS blockade group (7.5% vs 12.5%; log rank test, p=0.031). After adjusting for confounding factors, RAS blockade therapy was associated with significantly lower all-cause mortality (HR, 0.45; 95% CI 0.22 to 0.91; p=0.025). CONCLUSIONS: Postoperative RAS blockade therapy is associated with greater LV mass index regression and reduced all-cause mortality. These data need to be confirmed by a prospective randomised controlled outcome trial. PMID- 28986406 TI - Non-ischaemic cardiomyopathy, sudden death and implantable defibrillators: a review and meta-analysis. AB - OBJECTIVE: The recent Danish Study to Assess the Efficacy of ICDs in Patients with Non-ischemic Systolic Heart Failure on Mortality (DANISH) trial suggested that implantable cardioverter defibrillators (ICDs) do not reduce overall mortality in patients with non-ischaemic cardiomyopathy (NICM), despite reducing sudden cardiac death. We performed an updated meta-analysis to examine the impact of ICD therapy on mortality in NICM patients. METHODS: A systematic search for studies that examined the effect of ICDs on outcomes in NICM was performed. Our analysis compared patients randomised to an ICD with those randomised to no ICD, and examined the endpoint of overall mortality. RESULTS: Six primary prevention trials and two secondary prevention trials were identified that met the pre specified search criteria. Using a fixed-effects model, analysis of primary prevention trials revealed a reduction in overall mortality with ICD therapy (RR 0.76, 95% CI 0.65 to 0.91). CONCLUSIONS: Although our updated meta-analysis demonstrates a survival benefit of ICD therapy, the effect is substantively weakened by the inclusion of the DANISH trial-which is both the largest and most recent of the analysed trials-indicating that the residual pooled benefit of ICDs may reflect the risk of sudden death in older trials which included patients treated sub-optimally by contemporary standards. As such, these data must be interpreted cautiously. The results of the DANISH trial emphasise that there is no 'one size fits all' indication for primary prevention ICDs in NICM patients, and clinicians must consider age and comorbidity on an individual basis when determining whether a defibrillator is appropriate. PMID- 28986409 TI - Alzheimer dementia's other victim: The spouse. PMID- 28986407 TI - Ferumoxytol-enhanced magnetic resonance imaging in acute myocarditis. AB - OBJECTIVES: Ultrasmall superparamagnetic particles of iron oxide (USPIO)-enhanced MRI can detect tissue-resident macrophage activity and identify cellular inflammation within tissues. We hypothesised that USPIO-enhanced MRI would provide a non-invasive imaging technique that would improve the diagnosis and management of patients with acute myocarditis. METHODS: Ten volunteers and 14 patients with suspected acute myocarditis underwent T2, T2* and late gadolinium enhancement (LGE) 3T MRI, with further T2* imaging at 24 hours after USPIO (ferumoxytol, 4 mg/kg) infusion, at baseline and 3 months. Myocardial oedema and USPIO enhancement were determined within areas of LGE as well as throughout the myocardium. RESULTS: Myocarditis was confirmed in nine of the 14 suspected cases of myocarditis. There was greater myocardial oedema in regions of LGE in patients with myocarditis when compared with healthy volunteer myocardium (T2 value, 57.1+/-5.3 vs 46.7+/-1.6 ms, p<0.0001). There was no demonstrable difference in USPIO enhancement between patients and volunteers even within regions displaying LGE (change in R2*, 35.0+/-15.0 vs 37.2+/-9.6 s-1, p>0.05). Imaging after 3 months in patients with myocarditis revealed a reduction in volume of LGE, a reduction in oedema measures within regions displaying LGE and improvement in ejection fraction (mean -19.7 mL, 95% CI (-0.5 to -40.0)), -5.8 ms (-0.9 to 10.7) and +6% (0.5% to 11.5%), respectively, p<0.05 for all). CONCLUSION: In patients with acute myocarditis, USPIO-enhanced MRI does not provide additional clinically relevant information to LGE and T2 mapping MRI. This suggests that tissue-resident macrophages do not provide a substantial contribution to the myocardial inflammation in this condition.Clinical trial registration NCT02319278; Results. PMID- 28986408 TI - Prevalence and clinical features of neuromyelitis optica spectrum disorders in northern Japan. AB - OBJECTIVE: To clarify the prevalence and clinical characteristics of neuromyelitis optica spectrum disorders (NMOSD) in Japan and compare them with those in other ethnic populations. METHODS: Data processing sheets were sent to all related institutions in northern Japan and were collected from April to May 2016. Prevalence was determined on March 31, 2016, using the 2015 International Panel for NMO Diagnosis criteria. RESULTS: The crude prevalence was 4.1/100,000 (95% confidence interval 2.2-6.9) for NMOSD in northern Japan, with a significantly higher number of female than male patients (female: male 12:2). The positivity for anti-aquaporin-4 antibody was 78.6%, and the mean age at onset was 45.2 years. All patients were subjected to preventive therapy in the form of treatment with steroids or immunosuppressive agents. CONCLUSIONS: Our results showed that the prevalence of NMOSD in the Japanese population is similar to that in Caucasians. PMID- 28986410 TI - Thrombolysis in acute ischemic stroke in patients with dementia: A Swedish registry study. AB - OBJECTIVE: To compare access to intravenous thrombolysis (IVT) for acute ischemic stroke (AIS) and its outcomes in patients with and without dementia. METHODS: This was a longitudinal cohort study of the Swedish dementia and stroke registries. Patients with preexisting dementia who had AIS from 2010 to 2014 (n = 1,356) were compared with matched patients without dementia (n = 6,755). We examined access to thrombolysis and its outcomes at 3 months (death, residency, and modified Rankin Scale [mRS] score). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with logistic and ordinal logistic regression. RESULTS: The median age at stroke onset was 83 years in both groups. IVT was administered to 94 (7.0%) patients with dementia and 639 (9.5%) patients without dementia. The OR of receiving IVT was 0.68 (95% CI 0.54-0.86) for patients with dementia. When the analysis was repeated exclusively among patients independent in everyday activities, dementia status was no longer significant (OR 0.79, 95% CI 0.60-1.06). However, differences persisted in patients <=80 years of age (OR 0.58, 95% CI 0.36-0.94). In patients who received thrombolysis, the incidence of symptomatic intracerebral hemorrhage (sICH; 7.4% vs 7.3%) and death at 3 months (22.0% vs 18.8%) did not differ significantly between the 2 groups. However, mRS score and accommodation status were worse among patients with dementia after 3 months in adjusted analyses (both p < 0.001). Unfavorable outcomes with an mRS score of 5 to 6 were doubled in patients with dementia (56.1% vs 28.1%). CONCLUSIONS: Younger patients with dementia and AIS are less likely to receive IVT. Among patients receiving thrombolysis, there are no differences in sICH or death, although patients with dementia have worse accommodation and functional outcomes at 3 months. PMID- 28986412 TI - To sleep or not to sleep during deep brain stimulation surgery for Parkinson disease? PMID- 28986411 TI - Virtual reality improves embodiment and neuropathic pain caused by spinal cord injury. AB - OBJECTIVE: To investigate changes in body ownership and chronic neuropathic pain in patients with spinal cord injury (SCI) using multisensory own body illusions and virtual reality (VR). METHODS: Twenty patients with SCI with paraplegia and 20 healthy control participants (HC) participated in 2 factorial, randomized, repeated-measures design studies. In the virtual leg illusion (VLI), we applied asynchronous or synchronous visuotactile stimulation to the participant's back (either immediately above the lesion level or at the shoulder) and to the virtual legs as seen on a VR head-mounted display. We tested the effect of the VLI on the sense of leg ownership (questionnaires) and on perceived neuropathic pain (visual analogue scale pain ratings). We compared illusory leg ownership with illusory global body ownership (induced in the full body illusion [FBI]), by applying asynchronous or synchronous visuotactile stimulation to the participant's back and the back of a virtual body as seen on a head-mounted display. RESULTS: Our data show that patients with SCI are less sensitive to multisensory stimulations inducing illusory leg ownership (as compared to HC) and that leg ownership decreased with time since SCI. In contrast, we found no differences between groups in global body ownership as tested in the FBI. VLI and FBI were both associated with mild analgesia that was only during the VLI specific for synchronous visuotactile stimulation and the lower back position. CONCLUSIONS: The present findings show that VR exposure using multisensory stimulation differently affected leg vs body ownership, and is associated with mild analgesia with potential for SCI neurorehabilitation protocols. PMID- 28986413 TI - Comment: Is virtual reality a useful adjunct to rehabilitation after spinal cord injury? PMID- 28986414 TI - Prediction of work resumption and sustainability up to 1 year after mild traumatic brain injury. AB - OBJECTIVE: To study return to work (RTW) after mild traumatic brain injury (mTBI) at several intervals after injury and to predict RTW on the basis of occupational factors in addition to demographic, personality, and injury-related factors at 6 and 12 months after injury. METHODS: This was a prospective cohort study (UPFRONT study, n = 1,151) of patients with mTBI admitted to the emergency department. Patients received questionnaires at 2 weeks and 3, 6, and 12 months after injury. RTW was divided into 3 levels: complete (cRTW), partial (pRTW), and no RTW. RESULTS: Rates of cRTW increased from 34% at 2 weeks to 77% at 12 months after injury, pRTW varied from 8% to 16% throughout the year. Logistic regression (complete vs incomplete RTW) demonstrated that apart from previously identified predictors such as demographics (e.g., age and education) and injury characteristics (e.g., cause and severity of injury) and indicators of psychological distress, occupational factors were of influence on work resumption after 6 months (area under the curve [AUC] = 0.82), At 12 months, however, the model was based solely on the presence of extracranial injuries and indicators of maladaptation after injury (AUC = 0.81). CONCLUSIONS: RTW after mTBI is a gradual process, with varying levels of RTW throughout the first year after injury. Different predictors were relevant for short- vs long-term work resumption, with occupational factors influencing short-term RTW. However, for both short- and long-term RTW, posttraumatic complaints and signs of psychological distress early after injury were relevant predictors, allowing early identification of patients at risk for problematic work resumption. PMID- 28986415 TI - Clinical outcomes of asleep vs awake deep brain stimulation for Parkinson disease. AB - OBJECTIVE: To compare motor and nonmotor outcomes at 6 months of asleep deep brain stimulation (DBS) for Parkinson disease (PD) using intraoperative imaging guidance to confirm electrode placement vs awake DBS using microelectrode recording to confirm electrode placement. METHODS: DBS candidates with PD referred to Oregon Health & Science University underwent asleep DBS with imaging guidance. Six-month outcomes were compared to those of patients who previously underwent awake DBS by the same surgeon and center. Assessments included an "off" levodopa Unified Parkinson's Disease Rating Scale (UPDRS) II and III, the 39-item Parkinson's Disease Questionnaire, motor diaries, and speech fluency. RESULTS: Thirty participants underwent asleep DBS and 39 underwent awake DBS. No difference was observed in improvement of UPDRS III (+14.8 +/- 8.9 vs +17.6 +/- 12.3 points, p = 0.19) or UPDRS II (+9.3 +/- 2.7 vs +7.4 +/- 5.8 points, p = 0.16). Improvement in "on" time without dyskinesia was superior in asleep DBS (+6.4 +/- 3.0 h/d vs +1.7 +/- 1.2 h/d, p = 0.002). Quality of life scores improved in both groups (+18.8 +/- 9.4 in awake, +8.9 +/- 11.5 in asleep). Improvement in summary index (p = 0.004) and subscores for cognition (p = 0.011) and communication (p < 0.001) were superior in asleep DBS. Speech outcomes were superior in asleep DBS, both in category (+2.77 +/- 4.3 points vs -6.31 +/- 9.7 points (p = 0.0012) and phonemic fluency (+1.0 +/- 8.2 points vs -5.5 +/- 9.6 points, p = 0.038). CONCLUSIONS: Asleep DBS for PD improved motor outcomes over 6 months on par with or better than awake DBS, was superior with regard to speech fluency and quality of life, and should be an option considered for all patients who are candidates for this treatment. CLINICALTRIALSGOV IDENTIFIER: NCT01703598. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with PD undergoing DBS, asleep intraoperative CT imaging-guided implantation is not significantly different from awake microelectrode recording guided implantation in improving motor outcomes at 6 months. PMID- 28986417 TI - Cell-specific expression of runt-related transcription factor 2 contributes to pulmonary fibrosis. AB - Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease with limited therapeutic options and unknown etiology. IPF is characterized by epithelial cell injury, impaired cellular crosstalk between epithelial cells and fibroblasts, and the formation of fibroblast foci with increased extracellular matrix deposition (ECM). We investigated the role of runt-related transcription factor 2 (RUNX2), a master regulator of bone development that has been linked to profibrotic signaling. RUNX2 expression was up-regulated in lung homogenates from patients with IPF and in experimental bleomycin-induced lung fibrosis. The RUNX2 level correlated with disease severity as measured by decreased diffusing capacity and increased levels of the IPF biomarker, matrix metalloproteinase 7. Nuclear RUNX2 was observed in prosurfactant protein C-positive hyperplastic epithelial cells and was rarely found in myofibroblasts. We discovered an up-regulation of RUNX2 in fibrotic alveolar epithelial type II (ATII) cells as well as an increase of RUNX2-negative fibroblasts in experimental and human pulmonary fibrosis. Functionally, small interfering RNA-mediated RUNX2 knockdown decreased profibrotic ATII cell function, such as proliferation and migration, whereas fibroblasts displayed activation markers and increased ECM expression after RUNX2 knockdown. This study reveals that RUNX2 is differentially expressed in ATII cells vs. fibroblasts in lung fibrosis, which contributes to profibrotic cell function. Cell-specific targeting of RUNX2 pathways may represent a therapeutic approach for IPF.-Mummler, C., Burgy, O., Hermann, S., Mutze, K., Gunther, A., Konigshoff, M. Cell-specific expression of runt-related transcription factor 2 contributes to pulmonary fibrosis. PMID- 28986416 TI - Subjective cognitive decline and beta-amyloid burden predict cognitive change in healthy elderly. AB - OBJECTIVE: To assess in a longitudinal study whether subjective cognitive decline (SCD) and brain beta-amyloid (Abeta) contribute unique information to cognitive decline. METHODS: One hundred thirty-six healthy elderly from the Berkeley Aging Cohort Study were followed up for a mean of 4 years. SCD and affective measures were generated from the Geriatric Depression Scale (GDS) with factor analysis on data from a larger set of 347 healthy, nondepressed (GDS <11) elderly individuals. Cognition was summarized with previously validated factor scores. Pittsburgh compound B (PiB)-PET scans were acquired to determine the presence (PiB+) or absence (PiB-) of Abeta pathology. Mixed models were used to assess the independent and interactive effects of SCD, affective features, PiB status, and time on cognition, with adjustment for demographic variables. RESULTS: SCD score demonstrated good construct validity compared to an existing measure of subjective memory and was partially explained by several lower-order measurements. Mixed models revealed that SCD interacted with PiB status to predict change in episodic memory and global cognition over time, with adjustment for affective features. PiB+ individuals with more severe SCD demonstrated the steepest cognitive decline. Worse SCD predicted faster decline in working memory independently of PiB status. No such effects were seen for affective scores when adjusted for SCD. CONCLUSIONS: PiB+ individuals with SCD are at greatest risk of cognitive decline. Evidence for amyloid alone is not sufficient to indicate risk of rapid cognitive decline in healthy elderly. Effects of GDS on cognitive decline in nondepressed cohorts may be driven by SCD rather than subsyndromal depression. PMID- 28986418 TI - CD169+ macrophages orchestrate innate immune responses by regulating bacterial localization in the spleen. AB - The spleen is an important site for generating protective immune responses against pathogens. After infection, immune cells undergo rapid reorganization to initiate and maintain localized inflammatory responses; however, the mechanisms governing this spatial and temporal cellular reorganization remain unclear. We show that the strategic position of splenic marginal zone CD169+ macrophages is vital for rapid initiation of antibacterial responses. In addition to controlling initial bacterial growth, CD169+ macrophages orchestrate a second phase of innate protection by mediating the transport of bacteria to splenic T cell zones. This compartmentalization of bacteria within the spleen was essential for driving the reorganization of innate immune cells into hierarchical clusters and for local interferon-gamma production near sites of bacterial replication foci. Our results show that both phases of the antimicrobial innate immune response were dependent on CD169+ macrophages, and, in their absence, the series of events needed for pathogen clearance and subsequent survival of the host was disrupted. Our study provides insight into how lymphoid organ structure and function are related at a fundamental level. PMID- 28986420 TI - JAKing up resistance to immunotherapy. AB - A two-cell type CRISPR screen has identified genes and pathways that mediate resistance to cancer immunotherapy. PMID- 28986419 TI - Type III interferon is a critical regulator of innate antifungal immunity. AB - Type III interferons (IFN-lambdas) are the most recently found members of the IFN cytokine family and engage IFNLR1 and IL10R2 receptor subunits to activate innate responses against viruses. We have identified IFN-lambdas as critical instructors of antifungal neutrophil responses. Using Aspergillus fumigatus (Af) as a model to study antifungal immune responses, we found that depletion of CCR2+ monocytes compromised the ability of neutrophils to control invasive fungal growth. Using an unbiased approach, we identified type I and III IFNs as critical regulators of the interplay between monocytes and neutrophils responding to Af We found that CCR2+ monocytes are an important early source of type I IFNs that prime optimal expression of IFN-lambda. Type III IFNs act directly on neutrophils to activate their antifungal response, and mice with neutrophil-specific deletion of IFNLR1 succumb to invasive aspergillosis. Dysfunctional neutrophil responses in CCR2 depleted mice were rescued by adoptive transfer of pulmonary CCR2+ monocytes or by exogenous administration of IFN-alpha and IFN-lambda. Thus, CCR2+ monocytes promote optimal activation of antifungal neutrophils by initiating a coordinated IFN response. We have identified type III IFNs as critical regulators of neutrophil activation and type I IFNs as early stimulators of IFN-lambda expression. PMID- 28986421 TI - Stomatal VPD Response: There Is More to the Story Than ABA. AB - Guard cells shrink and close stomatal pores when air humidity decreases (i.e. when the difference between the vapor pressures of leaf and atmosphere [VPD] increases). The role of abscisic acid (ABA) in VPD-induced stomatal closure has been studied using ABA-related mutants that respond to VPD in some studies and not in others. The importance of ABA biosynthesis in guard cells versus vasculature for whole-plant stomatal regulation is unclear as well. Here, we show that Arabidopsis (Arabidopsis thaliana) lines carrying mutations in different steps of ABA biosynthesis as well as pea (Pisum sativum) wilty and tomato (Solanum lycopersicum) flacca ABA-deficient mutants had higher stomatal conductance compared with wild-type plants. To characterize the role of ABA production in different cells, we generated transgenic plants where ABA biosynthesis was rescued in guard cells or phloem companion cells of an ABA deficient mutant. In both cases, the whole-plant stomatal conductance, stunted growth phenotype, and leaf ABA level were restored to wild-type values, pointing to the redundancy of ABA sources and to the effectiveness of leaf ABA transport. All ABA-deficient lines closed their stomata rapidly and extensively in response to high VPD, whereas plants with mutated protein kinase OST1 showed stunted VPD induced responses. Another strongly ABA-insensitive mutant, defective in the six ABA PYR/RCAR receptors, responded to changes in VPD in both directions strongly and symmetrically, indicating that its VPD-induced closure could be passive hydraulic. We discuss that both the VPD-induced passive hydraulic stomatal closure and the stomatal VPD regulation of ABA-deficient mutants may be conditional on the initial pretreatment stomatal conductance. PMID- 28986422 TI - The Arabidopsis DNA Methylome Is Stable under Transgenerational Drought Stress. AB - Improving the responsiveness, acclimation, and memory of plants to abiotic stress holds substantive potential for improving agriculture. An unresolved question is the involvement of chromatin marks in the memory of agriculturally relevant stresses. Such potential has spurred numerous investigations yielding both promising and conflicting results. Consequently, it remains unclear to what extent robust stress-induced DNA methylation variation can underpin stress memory. Using a slow-onset water deprivation treatment in Arabidopsis (Arabidopsis thaliana), we investigated the malleability of the DNA methylome to drought stress within a generation and under repeated drought stress over five successive generations. While drought-associated epi-alleles in the methylome were detected within a generation, they did not correlate with drought-responsive gene expression. Six traits were analyzed for transgenerational stress memory, and the descendants of drought-stressed lineages showed one case of memory in the form of increased seed dormancy, and that persisted one generation removed from stress. With respect to transgenerational drought stress, there were negligible conserved differentially methylated regions in drought-exposed lineages compared with unstressed lineages. Instead, the majority of observed variation was tied to stochastic or preexisting differences in the epigenome occurring at repetitive regions of the Arabidopsis genome. Furthermore, the experience of repeated drought stress was not observed to influence transgenerational epi-allele accumulation. Our findings demonstrate that, while transgenerational memory is observed in one of six traits examined, they are not associated with causative changes in the DNA methylome, which appears relatively impervious to drought stress. PMID- 28986423 TI - Advances in Plant ER Architecture and Dynamics. PMID- 28986425 TI - Utilization of a Smartphone Platform for Electronic Informed Consent in Acute Stroke Trials. AB - BACKGROUND AND PURPOSE: The informed consent process is a major limitation for enrollment in acute stroke clinical investigations. We aim to describe the novel application of smartphone electronic informed consenting (e-Consent) in trials of cerebral thrombectomy. METHODS: The e-Consent tool consists of a secure/Health Insurance Portability and Accountability Act compliant smartphone platform based on REDCap (Research Electronic Data Capture; Vanderbilt University, TN) that uses a survey project located on a static webpage. A link to the webpage is sent via text message or email to the legally authorized representative. The e-Consent form is filled and a freehand electronic signature added in the smartphone browser; a record ID and an e-Consent Process Attestation form are automatically generated. The e-Consent application was piloted in a randomized trial comparing endovascular versus medical therapy in late presenting patients (DAWN [Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention With Trevo]). Trial enrollment began in January 2015; e-Consent was approved by the local institutional review board in December 2016, and the study was stopped in February 2017. RESULTS: During the trial period, Grady Memorial Hospital performed 273 thrombectomies with 47 patients being consented and 38 patients enrolled in the DAWN trial. Of the randomized patients, 29 (76%) were transferred from outside hospitals. A total of 6 surrogates were e Consented, with 2 patients being screen failures. Enrolled e-Consented patients (n=4) had similar age (73+/-14 versus 69+/-12 years; P=0.65) and National Institutes of Health Stroke Scale (16+/-5 versus 16+/-5; P=0.88) as compared with conventionally consented (n=25). Time from door-to-randomization was decreased with e-Consenting (28+/-9 versus 57+/-24 minutes; P=0.002). CONCLUSIONS: e Consenting streamlined the consenting process in a randomized trial of patients with emergent large vessel occlusion strokes. PMID- 28986426 TI - Increase of Stroke Incidence in Young Adults in a Middle-Income Country: A 10 Year Population-Based Study. AB - BACKGROUND AND PURPOSE: The incidence of stroke is on the rise in young adults in high-income countries. However, there is a gap of knowledge about trends in stroke incidence in young adults from low- and middle-income countries. We aimed to measure trends in incidence of ischemic stroke (IS) and intracerebral hemorrhage (IH) in young people from 2005 to 2015 in Joinville, Brazil. METHODS: We retrospectively ascertained all first-ever IS subtypes and IH that occurred in Joinville in the periods of 2005 to 2006, 2010 to 2011, and 2014 to 2015. Poisson regression was used to calculate incidence rate ratios of all strokes, IS, and IH. We also compared the prevalence of risk factors and extension of diagnostic work-up across the 3 periods. RESULTS: For 10 years, we registered 2483 patients (7.5% aged <45 years). From 2005 to 2006 to 2014 to 2015, overall stroke incidence significantly increased by 62% (incidence rate ratios, 1.62; 95% confidence interval, 1.10-2.40) in subjects <45 years and by 29% in those <55 years (incidence rate ratios, 1.29; 95% confidence interval, 1.04-1.60). Incidence of IS increased by 66% (incidence rate ratios, 1.66; 95% confidence interval, 1.09-2.54), but there was no significant change in incidence of IH in subjects <45 years. Smoking rates decreased by 71% (odds ratio, 0.29; 95% confidence interval, 0.12-0.68). CONCLUSIONS: Stroke incidence is rising in young adults in Joinville, Brazil, because of increase in rates of ischemic but not hemorrhagic strokes. We urgently need better policies of cardiovascular prevention in the young. PMID- 28986424 TI - Floral Metabolism of Sugars and Amino Acids: Implications for Pollinators' Preferences and Seed and Fruit Set. PMID- 28986427 TI - Comprehensive background check policy and firearm background checks in three US states. AB - BACKGROUND: Comprehensive background check (CBC) policies are hypothesised to reduce firearm-related violence because they extend background checks to private party firearm sales, but no study has determined whether these policies actually increase background checks, an expected intermediary outcome. We evaluate the association between CBC policies and the rates of firearm background checks in three states that recently implemented these policies: Delaware (July 2013), Colorado (July 2013) and Washington (December 2014). METHODS: We used the synthetic control group method to estimate the difference from estimated counterfactual postintervention trends in the monthly rate of background checks per 1 00 000 people for handguns, long guns and both types combined, using data for January 1999 through December 2016. Inference was based on results from permutation tests. We conducted multiple sensitivity analyses to assess the robustness of our results. RESULTS: Background check rates increased in Delaware, by 22%-34% depending on the type of firearm, following enactment of its CBC law. No overall changes were observed in Washington and Colorado. Our results were robust to changes in the comparison group and statistical methods. CONCLUSIONS: The enactment of CBC policies was associated with an overall increase in firearm background checks only in Delaware. Data external to the study suggest that Washington experienced a modest, but consistent, increase in background checks for private party sales, and Colorado experienced a similar increase in checks for sales not at gun shows. Non-compliance may explain the lack of an overall increase in background checks in Washington and Colorado. PMID- 28986428 TI - Injury upon injury: a prospective cohort study examining subsequent injury claims in the 24 months following a substantial injury. AB - OBJECTIVES: This study examines subsequent injuries reported to the Accident Compensation Corporation (ACC), New Zealand's universal no-fault injury insurer, in the 24 months following an ACC entitlement claim injury event. Specific aims were to determine the: (1) 12 and 24 month cumulative incidence of at least one ACC-reported subsequent injury (ACC-SUBS-Inj), (2) characteristics of participants with and without ACC-SUBS-Inj, (3) frequency of ACC-SUBS-Inj, (4) time periods in which people are at higher risk of ACC-SUBS-Inj and (5) types of ACC-SUBS-Inj. METHODS: Interview data collected directly from participants in the Prospective Outcomes of Injury Study (POIS) were combined with ACC-SUBS-Inj data from ACC and hospital discharge datasets. A subsequent injury was defined as any injury event resulting in an ACC claim within 24 months following the injury event for which participants were recruited to POIS (the sentinel injury). All ACC-SUBS-Inj were included irrespective of whether they were the same as the sentinel injury or not. RESULTS: Of 2856 participants, 58% (n=1653) experienced at least one ACC-SUBS-Inj in 24 months; 31% (n=888) had more than one ACC-SUBS Inj. The time period of lowest risk of ACC-SUBS-Inj was the first 3 months following the sentinel injury event. Spine sprain/strain was the type of injury with the greatest number of ACC-SUBS-Inj claims per person. CONCLUSIONS: More than half of those with an ACC entitlement claim injury incurred further injury events that resulted in a claim in the following 24 months. Greater understanding of these subsequent injury events provides an avenue for injury prevention. PMID- 28986429 TI - Characterising violent deaths of undetermined intent: a population-based study, 1999-2012. AB - OBJECTIVES: Violent deaths classified as undetermined intent (UD) are sometimes included in suicide counts. This study investigated age and sex differences, along with socioeconomic gradients in UD and suicide deaths in the province of Ontario between 1999 and 2012. METHODS: We used data from the Institute for Clinical Evaluative Sciences, which has linked vital statistics from the Office of the Registrar General Deaths register with Census data between 1999 and 2012. Socioeconomic status was operationalised through the four dimensions of the Ontario Marginalization Index. We computed age-specific and annual age standardised mortality rates, and risk ratios to calculate risk gradients according to each of the four dimensions of marginalization. RESULTS: Rates of UD classified deaths were highest for men aged 45-64 years residing in the most materially deprived (7.9 per 100 000 population (95% CI 6.8 to 9.0)) and residentially unstable (8.1 (95% CI 7.1 to 9.1)) neighbourhoods. Similarly, suicide rates were highest among these same groups of men aged 45-64 living in the most materially deprived (28.2 (95% CI 26.1 to 30.3)) and residentially unstable (30.7 (95% CI 28.7 to 32.6)) neighbourhoods. Relative to methods of death, poisoning was the most frequently used method in UD cases (64%), while it represented the second most common method (27%) among suicides after hanging (40%). DISCUSSION: The similarities observed between both causes of death suggest that at least a proportion of UD deaths may be misclassified suicide cases. However, the discrepancies identified in this analysis seem to indicate that not all UD deaths are misclassified suicides. PMID- 28986430 TI - How entry inhibitors synergize to fight HIV. AB - HIV fusion with the cell membrane can be inhibited by blocking coreceptor binding or by preventing fusion-inducing conformational changes in the Env protein. Logically, inhibitors that act by these two mechanisms should act synergistically, but previous studies have reported conflicting results. A new study by Ahn and Root reconciles these discordant reports by demonstrating that synergy emerges when Env engages multiple coreceptors prior to inducing fusion and when high-affinity inhibitory peptides are used, a condition that may not be satisfied in vivo. PMID- 28986431 TI - A novel antithrombin domain dictates the journey's end of a proteinase. AB - Antithrombin (AT) is an anticoagulant serpin that irreversibly inactivates the clotting proteinases factor Xa and thrombin by forming covalent complexes with them. Mutations in its critical domains, such as those that impair the conformational rearrangement required for proteinase inactivation, increase the risk of venous thrombosis. Aguila et al. characterize for the first time the destabilizing effects of mutations in the region of AT that makes contact with the proteinase in the final acyl-enzyme complex. Their work adds new insight into the unique structural intricacies of the inhibitory mechanism. PMID- 28986432 TI - Adaptor protein CD2AP and L-type lectin LMAN2 regulate exosome cargo protein trafficking through the Golgi complex. PMID- 28986433 TI - O-GlcNAcase is an RNA polymerase II elongation factor coupled to pausing factors SPT5 and TIF1beta. PMID- 28986434 TI - Molecular identification and functional characterization of the human colonic thiamine pyrophosphate transporter. PMID- 28986435 TI - Relationship between smoking and health and education spending in Chile. AB - OBJECTIVE: To estimate the degree to which tobacco consumption is associated with spending on a set of goods and services in Chile, especially health and education, for the total population as well as for specific subgroups. METHODS: A seemingly unrelated regression equation system was used to estimate the statistical relationship between having tobacco expenditures and the budget share allocated to other items for the total population and for specific subgroups in Chile (eg, households within the bottom/top 33% by total expenditures). The use of household-level data allows for the control of a number of sociodemographic characteristics. The nationally representative 2012 Chilean Household Expenditure Survey was used for the analysis. RESULTS: Tobacco consumption is associated with lower budget shares allocated to healthcare, education and housing expenses, especially for poorer households. In the case of health, not consuming tobacco is related to higher health expenditures: up to 32% for the total population. Similarly, in the case of education, not consuming tobacco is statistically related to higher education expenditures: up to 16% for the total population. For all groups, tobacco consumption is also related to a significantly higher budget share allocated to alcoholic beverages. CONCLUSIONS: The strong significant statistical relationship found between tobacco consumption and resources allocated to healthcare and education consumption may be indicative of the existence of a crowding out effect of tobacco. This effect, in turn, may increase the burden that the rest of society must bear for the increased healthcare that they require because of tobacco consumption. PMID- 28986436 TI - Normal human adipose tissue functions and differentiation in patients with biallelic LPIN1 inactivating mutations. AB - Lipin-1 is a Mg2+-dependent phosphatidic acid phosphatase (PAP) that in mice is necessary for normal glycerolipid biosynthesis, controlling adipocyte metabolism, and adipogenic differentiation. Mice carrying inactivating mutations in the Lpin1 gene display the characteristic features of human familial lipodystrophy. Very little is known about the roles of lipin-1 in human adipocyte physiology. Apparently, fat distribution and weight is normal in humans carrying LPIN1 inactivating mutations, but a detailed analysis of adipose tissue appearance and functions in these patients has not been available so far. In this study, we performed a systematic histopathological, biochemical, and gene expression analysis of adipose tissue biopsies from human patients harboring LPIN1 biallelic inactivating mutations and affected by recurrent episodes of severe rhabdomyolysis. We also explored the adipogenic differentiation potential of human mesenchymal cell populations derived from lipin-1 defective patients. White adipose tissue from human LPIN1 mutant patients displayed a dramatic decrease in lipin-1 protein levels and PAP activity, with a concomitant moderate reduction of adipocyte size. Nevertheless, the adipose tissue develops without obvious histological signs of lipodystrophy and with normal qualitative composition of storage lipids. The increased expression of key adipogenic determinants such as SREBP1, PPARG, and PGC1A shows that specific compensatory phenomena can be activated in vivo in human adipocytes with deficiency of functional lipin-1. PMID- 28986438 TI - Decidual T Cells Exhibit a Highly Differentiated Phenotype and Demonstrate Potential Fetal Specificity and a Strong Transcriptional Response to IFN. AB - Immune tolerance during human pregnancy is maintained by a range of modifications to the local and systemic maternal immune system. Lymphoid infiltration is seen at the implantation site of the fetal-maternal interface, and decidual NK cells have been demonstrated to facilitate extravillous trophoblast invasion into maternal decidua during the first trimester, optimizing hemochorial placentation. However, although there is considerable T cell infiltration of the maternal decidua, the functional properties of this T cell response remain poorly defined. We investigated the specificity and regulation of CD4+ and CD8+ T cells obtained from human third trimester decidua and demonstrated that decidual CD4+ and CD8+ T cells exhibit a highly differentiated effector memory phenotype in comparison with peripheral blood and display increased production of IFN-gamma and IL-4. Moreover, decidual T cells proliferated in response to fetal tissue, and depletion of T regulatory cells led to an increase in fetal-specific proliferation. HY-specific T cells were detectable in the decidua of women with male pregnancies and were shown to be highly differentiated. Transcriptional analysis of decidual T cells revealed a unique gene profile characterized by elevated expression of proteins associated with the response to IFN signaling. These data have considerable importance both for the study of healthy placentation and for the investigation of the potential importance of fetal specific alloreactive immune responses within disorders of pregnancy. PMID- 28986439 TI - Filamin A Regulates Neutrophil Adhesion, Production of Reactive Oxygen Species, and Neutrophil Extracellular Trap Release. AB - Neutrophils are of fundamental importance in the early immune response and use various mechanisms to neutralize invading pathogens. They kill endocytosed pathogens by releasing reactive oxygen species in the phagosome and release neutrophil extracellular traps (NETs) into their surroundings to immobilize and kill invading micro-organisms. Filamin A (FlnA) is an important actin cross linking protein that is required for cellular processes involving actin rearrangements, such cell migration. It has also been shown to negatively regulate integrin activation and adhesion. However, its role in the regulation of beta2 integrin-dependent adhesion, as well as in other cellular functions in neutrophils, is poorly understood. Using a transgenic mouse model in which FlnA is selectively depleted in myeloid cells, such as neutrophils, we show that FlnA negatively regulates beta2 integrin adhesion to complement component iC3b and ICAM-1 in shear-free, but not shear-flow, conditions. FlnA deletion does not affect phagocytosis of Escherichia coli or Staphylococcus aureus or their intracellular killing. However, FlnA negatively regulates production of reactive oxygen species upon cell activation. Conversely, neutrophil activation through TLR4, as well as through activation by the Gram-negative bacteria E. coli, results in reduced NET production in FlnA-depleted neutrophils. Thus, FlnA is a negative regulator of beta2 integrin-dependent cell adhesion and reactive oxygen species production but is required for NET production in primary murine neutrophils. PMID- 28986441 TI - Changes in Influenza Vaccination Rates After Withdrawal of Live Vaccine. AB - BACKGROUND: Before the start of the 2016-2017 influenza season, the Advisory Committee on Immunization Practices withdrew its recommendation promoting the use of live attenuated influenza vaccines (LAIVs). There was concern that this might lessen the likelihood that those with a previous LAIV would return for an injectable influenza vaccine (IIV) and that child influenza immunization rates would decrease overall. METHODS: Using Oregon's statewide immunization registry, the ALERT Immunization Information System, child influenza immunization rates were compared across the 2012-2013 through 2016-2017 seasons. Additionally, matched cohorts of children were selected based on receipt of either an LAIV or an IIV during the 2015-2016 season. Differences between the IIV and LAIV cohorts in returning for the IIV in the 2016-2017 season were assessed. RESULTS: Overall, influenza immunization rates for children aged 2 to 17 years were unchanged between the 2015-2016 and 2016-2017 seasons. Children aged 3 to 10 with a previous IIV were 1.03 (95% confidence interval, 1.02 to 1.04) times more likely to return for an IIV in 2016-2017 than those with a previous LAIV, whereas children aged 11 to 17 years with a previous IIV were 1.08 (95% confidence interval, 1.05 to -1.09) times more likely to return. CONCLUSIONS: Withdrawal of the LAIV recommendation was not associated with an overall change in child influenza immunization rates across seasons. Children with a previous (2015-2016) IIV were slightly more likely to return during the 2016-2017 season for influenza immunization than those with a previous LAIV. PMID- 28986440 TI - Genetic Control of Lyme Arthritis by Borrelia burgdorferi Arthritis-Associated Locus 1 Is Dependent on Localized Differential Production of IFN-beta and Requires Upregulation of Myostatin. AB - Previously, using a forward genetic approach, we identified differential expression of type I IFN as a positional candidate for an expression quantitative trait locus underlying Borrelia burgdorferi arthritis-associated locus 1 (Bbaa1). In this study, we show that mAb blockade revealed a unique role for IFN-beta in Lyme arthritis development in B6.C3-Bbaa1 mice. Genetic control of IFN-beta expression was also identified in bone marrow-derived macrophages stimulated with B. burgdorferi, and it was responsible for feed-forward amplification of IFN stimulated genes. Reciprocal radiation chimeras between B6.C3-Bbaa1 and C57BL/6 mice revealed that arthritis is initiated by radiation-sensitive cells, but orchestrated by radiation-resistant components of joint tissue. Advanced congenic lines were developed to reduce the physical size of the Bbaa1 interval, and confirmed the contribution of type I IFN genes to Lyme arthritis. RNA sequencing of resident CD45- joint cells from advanced interval-specific recombinant congenic lines identified myostatin as uniquely upregulated in association with Bbaa1 arthritis development, and myostatin expression was linked to IFN-beta production. Inhibition of myostatin in vivo suppressed Lyme arthritis in the reduced interval Bbaa1 congenic mice, formally implicating myostatin as a novel downstream mediator of the joint-specific inflammatory response to B. burgdorferi. PMID- 28986437 TI - Harmonizing lipidomics: NIST interlaboratory comparison exercise for lipidomics using SRM 1950-Metabolites in Frozen Human Plasma. AB - As the lipidomics field continues to advance, self-evaluation within the community is critical. Here, we performed an interlaboratory comparison exercise for lipidomics using Standard Reference Material (SRM) 1950-Metabolites in Frozen Human Plasma, a commercially available reference material. The interlaboratory study comprised 31 diverse laboratories, with each laboratory using a different lipidomics workflow. A total of 1,527 unique lipids were measured across all laboratories and consensus location estimates and associated uncertainties were determined for 339 of these lipids measured at the sum composition level by five or more participating laboratories. These evaluated lipids detected in SRM 1950 serve as community-wide benchmarks for intra- and interlaboratory quality control and method validation. These analyses were performed using nonstandardized laboratory-independent workflows. The consensus locations were also compared with a previous examination of SRM 1950 by the LIPID MAPS consortium. While the central theme of the interlaboratory study was to provide values to help harmonize lipids, lipid mediators, and precursor measurements across the community, it was also initiated to stimulate a discussion regarding areas in need of improvement. PMID- 28986442 TI - The Effect of Reduction Mammaplasty on Quality of Life in Adolescents With Macromastia. AB - OBJECTIVES: To measure changes in health-related quality of life and breast related symptoms after reduction mammaplasty in adolescents. METHODS: In this longitudinal cohort study, we administered the Short-Form 36v2 (SF-36), Rosenberg Self-Esteem Scale (RSES), Breast-Related Symptoms Questionnaire (BRSQ), and Eating Attitudes Test-26 to 102 adolescents with macromastia and 84 female controls, aged 12 to 21 years. Patients with macromastia completed surveys preoperatively and after reduction mammaplasty at 6 months and 1, 3, and 5 years. Controls completed baseline and follow-up surveys at the same intervals. RESULTS: Patients with macromastia demonstrated significant score improvements postoperatively from baseline on the RSES, BRSQ, and in 7 out of 8 SF-36 domains: physical functioning, role-physical, bodily pain, vitality, social functioning, role-emotional, mental health (P < .001, all). By the 6-month follow-up visit, postoperative subjects scored similarly to or more favorably than controls on the RSES, BRSQ, Eating Attitudes Test-26 , and SF-36; these benefits persisted for at least 5 years and were not significantly affected by BMI category or age. CONCLUSIONS: Reduction mammaplasty was significantly associated with improvements in health-related quality of life and breast-related symptoms of adolescent patients, with measureable improvements in physical and psychosocial well-being evident by 6 months postoperatively and still demonstrable after 5-years. These results largely do not vary by BMI category or age. Patients and providers should be aware of the potential positive impact that reduction mammaplasty can provide adolescents with symptomatic macromastia. Historic concerns regarding age and BMI category at the time of surgery should be reconsidered. PMID- 28986443 TI - Competitive Ability of Maize Pollen Grains Requires Paralogous Serine Threonine Protein Kinases STK1 and STK2. AB - serine threonine kinase1 (stk1) and serine threonine kinase2 (stk2) are closely related maize paralogous genes predicted to encode serine/threonine protein kinases. Pollen mutated in stk1 or stk2 competes poorly with normal pollen, pointing to a defect in pollen tube germination or growth. Both genes are expressed in pollen, but not in most other tissues. In germination media, STK1 and STK2 fluorescent fusion proteins localize to the plasma membrane of the vegetative cell. RNA-seq experiments identified 534 differentially expressed genes in stk1 mutant pollen relative to wild type. Gene ontology (GO) molecular functional analysis uncovered several differentially expressed genes with putative ribosome initiation and elongation functions, suggesting that stk1 might affect ribosome function. Of the two paralogs, stk1 may play a more important role in pollen development than stk2, as stk2 mutations have a smaller pollen transmission effect. However, stk2 does act as an enhancer of stk1 because the double mutant combination is only infrequently pollen-transmitted in double heterozygotes. We conclude that the stk paralogs play an essential role in pollen development. PMID- 28986444 TI - Metabolomic Analysis Reveals That the Drosophila melanogaster Gene lysine Influences Diverse Aspects of Metabolism. AB - The fruit fly Drosophila melanogaster has emerged as a powerful model for investigating the molecular mechanisms that regulate animal metabolism. However, a major limitation of these studies is that many metabolic assays are tedious, dedicated to analyzing a single molecule, and rely on indirect measurements. As a result, Drosophila geneticists commonly use candidate gene approaches, which, while important, bias studies toward known metabolic regulators. In an effort to expand the scope of Drosophila metabolic studies, we used the classic mutant lysine (lys) to demonstrate how a modern metabolomics approach can be used to conduct forward genetic studies. Using an inexpensive and well-established gas chromatography-mass spectrometry-based method, we genetically mapped and molecularly characterized lys by using free lysine levels as a phenotypic readout. Our efforts revealed that lys encodes the Drosophila homolog of Lysine Ketoglutarate Reductase/Saccharopine Dehydrogenase, which is required for the enzymatic degradation of lysine. Furthermore, this approach also allowed us to simultaneously survey a large swathe of intermediate metabolism, thus demonstrating that Drosophila lysine catabolism is complex and capable of influencing seemingly unrelated metabolic pathways. Overall, our study highlights how a combination of Drosophila forward genetics and metabolomics can be used for unbiased studies of animal metabolism, and demonstrates that a single enzymatic step is intricately connected to diverse aspects of metabolism. PMID- 28986445 TI - Histone H3 Threonine 11 Phosphorylation Is Catalyzed Directly by the Meiosis Specific Kinase Mek1 and Provides a Molecular Readout of Mek1 Activity in Vivo. AB - Saccharomyces cerevisiae Mek1 is a CHK2/Rad53-family kinase that regulates meiotic recombination and progression upon its activation in response to DNA double-strand breaks (DSBs). The full catalog of direct Mek1 phosphorylation targets remains unknown. Here, we show that phosphorylation of histone H3 on threonine 11 (H3 T11ph) is induced by meiotic DSBs in S. cerevisiae and Schizosaccharomyces pombe Molecular genetic experiments in S. cerevisiae confirmed that Mek1 is required for H3 T11ph and revealed that phosphorylation is rapidly reversed when Mek1 kinase is no longer active. Reconstituting histone phosphorylation in vitro with recombinant proteins demonstrated that Mek1 directly catalyzes H3 T11 phosphorylation. Mutating H3 T11 to nonphosphorylatable residues conferred no detectable defects in otherwise unperturbed meiosis, although the mutations modestly reduced spore viability in certain strains where Rad51 is used for strand exchange in place of Dmc1. H3 T11ph is therefore mostly dispensable for Mek1 function. However, H3 T11ph provides an excellent marker of ongoing Mek1 kinase activity in vivo Anti-H3 T11ph chromatin immunoprecipitation followed by deep sequencing demonstrated that H3 T11ph was highly enriched at presumed sites of attachment of chromatin to chromosome axes, gave a more modest signal along chromatin loops, and was present at still lower levels immediately adjacent to DSB hotspots. These localization patterns closely tracked the distribution of Red1 and Hop1, axis proteins required for Mek1 activation. These findings provide insight into the spatial disposition of Mek1 kinase activity and the higher order organization of recombining meiotic chromosomes. PMID- 28986446 TI - The SecA protein deeply penetrates into the SecYEG channel during insertion, contacting most channel transmembrane helices and periplasmic regions. AB - The bacterial Sec-dependent system is the major protein-biogenic pathway for protein secretion across the cytoplasmic membrane or insertion of integral membrane proteins into the phospholipid bilayer. The mechanism of SecA-driven protein transport across the SecYEG channel complex has remained controversial with conflicting claims from biochemical and structural studies regarding the depth and extent of SecA insertion into SecYEG during ongoing protein transport. Here we utilized site-specific in vivo photo-crosslinking to thoroughly map SecY regions that are in contact with SecA during its insertion cycle. An arabinose inducible, rapidly folding OmpA-GFP chimera was utilized to jam the SecYEG channels with an arrested substrate protein to "freeze" them in their SecA inserted state. Examination of 117 sites distributed throughout SecY indicated that SecA not only interacts extensively with the cytosolic regions of SecY as shown previously, but it also interacts with most of the transmembrane helices and periplasmic regions of SecY, with a clustering of interaction sights around the lateral gate and pore ring regions. Our observations support previous reports of SecA membrane insertion during in vitro protein transport as well as those documenting the membrane penetration properties of this protein. They suggest that one or more SecA regions transiently integrate into the heart of the SecY channel complex to span the membrane to promote the protein transport cycle. These findings indicate that high-resolution structural information about the membrane-inserted state of SecA is still lacking and will be critical for elucidating the bacterial protein transport mechanism. PMID- 28986447 TI - Innate immune recognition of double-stranded RNA triggers increased expression of NKG2D ligands after virus infection. AB - Self/non-self-discrimination by the innate immune system relies on germline encoded, non-rearranging receptors expressed by innate immune cells recognizing conserved pathogen-associated molecular patterns. The natural killer group 2D (NKG2D) receptor is a potent immune-activating receptor that binds human genome encoded ligands, whose expression is negligible in normal tissues, but increased in stress and disease conditions for reasons that are incompletely understood. Here it is not clear how the immune system reconciles receptor binding of self proteins with self/non-self-discrimination to avoid autoreactivity. We now report that increased expression of NKG2D ligands after virus infection depends on interferon response factors activated by the detection of viral double-stranded RNA by pattern-recognition receptors (RIG-I/MDA-5) and that NKG2D ligand up regulation can be blocked by the expression of viral dsRNA-binding proteins. Thus, innate immunity-mediated recognition of viral nucleic acids triggers the infected cell to release interferon for NK cell recruitment and to express NKG2D ligands to become more visible to the immune system. Finally, the observation that NKG2D-ligand induction is a consequence of signaling by pattern-recognition receptors that have been selected over evolutionary time to be highly pathogen specific explains how the risks of autoreactivity in this system are minimized. PMID- 28986448 TI - An improved Escherichia coli screen for Rubisco identifies a protein-protein interface that can enhance CO2-fixation kinetics. AB - An overarching goal of photosynthesis research is to identify how components of the process can be improved to benefit crop productivity, global food security, and renewable energy storage. Improving carbon fixation has mostly focused on enhancing the CO2 fixing enzyme ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco). This grand challenge has mostly proved ineffective because of catalytic mechanism constraints and required chaperone complementarity that hinder Rubisco biogenesis in alternative hosts. Here we refashion Escherichia coli metabolism by expressing a phosphoribulokinase-neomycin phosphotransferase fusion protein to produce a high-fidelity, high-throughput Rubisco-directed evolution (RDE2) screen that negates false-positive selection. Successive evolution rounds using the plant-like Te-Rubisco from the cyanobacterium Thermosynechococcus elongatus BP1 identified two large subunit and six small subunit mutations that improved carboxylation rate, efficiency, and specificity. Structural analysis revealed the amino acids clustered in an unexplored subunit interface of the holoenzyme. To study its effect on plant growth, the Te-Rubisco was transformed into tobacco by chloroplast transformation. As previously seen for Synechocccus PCC6301 Rubisco, the specialized folding and assembly requirements of Te-Rubisco hinder its heterologous expression in leaf chloroplasts. Our findings suggest that the ongoing efforts to improve crop photosynthesis by integrating components of a cyanobacteria CO2-concentrating mechanism will necessitate co-introduction of the ancillary molecular components required for Rubisco biogenesis. PMID- 28986450 TI - STAP-2 protein promotes prostate cancer growth by enhancing epidermal growth factor receptor stabilization. AB - Signal-transducing adaptor family member-2 (STAP-2) is an adaptor protein that regulates various intracellular signaling pathways and promotes tumorigenesis in melanoma and breast cancer cells. However, the contribution of STAP-2 to the behavior of other types of cancer cells is unclear. Here, we show that STAP-2 promotes tumorigenesis of prostate cancer cells through up-regulation of EGF receptor (EGFR) signaling. Tumor growth of a prostate cancer cell line, DU145, was strongly decreased by STAP-2 knockdown. EGF-induced gene expression and phosphorylation of AKT, ERK, and STAT3 were significantly decreased in STAP-2 knockdown DU145 cells. Mechanistically, we found that STAP-2 interacted with EGFR and enhanced its stability by inhibiting c-CBL-mediated EGFR ubiquitination. Our results indicate that STAP-2 promotes prostate cancer progression via facilitating EGFR activation. PMID- 28986449 TI - Mfd translocase is necessary and sufficient for transcription-coupled repair in Escherichia coli. AB - Nucleotide excision repair in Escherichia coli is stimulated by transcription, specifically in the transcribed strand. Previously, it was shown that this transcription-coupled repair (TCR) is mediated by the Mfd translocase. Recently, it was proposed that in fact the majority of TCR in E. coli is catalyzed by a second pathway ("backtracking-mediated TCR") that is dependent on the UvrD helicase and the guanosine pentaphosphate (ppGpp) alarmone/stringent response regulator. Recently, we reported that as measured by the excision repair sequencing (XR-seq), UvrD plays no role in TCR genome-wide. Here, we tested the role of ppGpp and UvrD in TCR genome-wide and in the lacZ operon using the XR-seq method, which directly measures repair. We found that the mfd mutation abolishes TCR genome-wide and in the lacZ operon. In contrast, the relA-spoT- mutant deficient in ppGpp synthesis carries out normal TCR. We conclude that UvrD and ppGpp play no role in TCR in E. coli. PMID- 28986451 TI - Impact of Selection Bias on Estimation of Subsequent Event Risk. AB - BACKGROUND: Studies of recurrent or subsequent disease events may be susceptible to bias caused by selection of subjects who both experience and survive the primary indexing event. Currently, the magnitude of any selection bias, particularly for subsequent time-to-event analysis in genetic association studies, is unknown. METHODS AND RESULTS: We used empirically inspired simulation studies to explore the impact of selection bias on the marginal hazard ratio for risk of subsequent events among those with established coronary heart disease. The extent of selection bias was determined by the magnitudes of genetic and nongenetic effects on the indexing (first) coronary heart disease event. Unless the genetic hazard ratio was unrealistically large (>1.6 per allele) and assuming the sum of all nongenetic hazard ratios was <10, bias was usually <10% (downward toward the null). Despite the low bias, the probability that a confidence interval included the true effect decreased (undercoverage) with increasing sample size because of increasing precision. Importantly, false-positive rates were not affected by selection bias. CONCLUSIONS: In most empirical settings, selection bias is expected to have a limited impact on genetic effect estimates of subsequent event risk. Nevertheless, because of undercoverage increasing with sample size, most confidence intervals will be over precise (not wide enough). When there is no effect modification by history of coronary heart disease, the false-positive rates of association tests will be close to nominal. PMID- 28986452 TI - Care in Specialized Centers and Data Sharing Increase Agreement in Hypertrophic Cardiomyopathy Genetic Test Interpretation. AB - BACKGROUND: Clinically impactful differences in the interpretation of genetic test results occur between laboratories and clinicians. To improve the classification of variants, a better understanding of why discrepancies occur and how they can be reduced is needed. METHODS AND RESULTS: We examined the frequency, causes, and resolution of discordant variant classifications in the Sarcomeric Human Cardiomyopathy Registry (SHaRe), a consortium of international centers with expertise in the clinical management and genetic architecture of hypertrophic cardiomyopathy. Of the 112 variants present in patients at >1 center, 23 had discordant classifications among centers (20.5%; Fleiss kappa, 0.54). Discordance was more than twice as frequent among clinical laboratories in ClinVar, a public archive of variant classifications (315/695 variants; 45.2%; Fleiss kappa, 0.30; P<0.001). Discordance in SHaRe most frequently occurred because hypertrophic cardiomyopathy centers had access to different privately held data when making their classifications (75.0%). Centers reassessed their classifications based on a comprehensive and current data summary, leading to reclassifications that reduced the discordance rate from 20.5% to 10.7%. Different interpretations of rarity and co-occurrence with pathogenic variants contributed to residual discordance. CONCLUSIONS: Discordance in variant classification among hypertrophic cardiomyopathy centers is largely attributable to privately held data. Some discrepancies are caused by differences in expert assessment of conflicting data. Discordance was markedly lower among centers specialized in hypertrophic cardiomyopathy than among clinical laboratories, suggesting that optimal genetic test interpretation occurs in the context of clinical care delivered by specialized centers with both clinical and genetics expertise. PMID- 28986454 TI - Validation of Polygenic Scores for QT Interval in Clinical Populations. AB - BACKGROUND: Polygenic risk scores (PGS) enable rapid estimation of genome-wide susceptibility for traits, which may be useful in clinical settings, such as prediction of QT interval. In this study, we sought to validate PGS for QT interval in 2 real-world cohorts of European ancestry (EA) and African ancestry (AA). METHODS AND RESULTS: Two thousand nine hundred and fifteen participants of EA and 366 of AA in the MGH CAMP study (Cardiology and Metabolic Patient) were genotyped on a genome-wide array and imputed to the 1000 Genomes reference panel. An additional 820 EA and 57 AA participants in the Partners Biobank were genotyped and used for validation. PGS were created for each individual using effect estimates from association tests with QT interval obtained from prior genome-wide association studies, with variants selected based from multiple significance thresholds in the original study. In regression models, clinical variables explained ~9% to 10% of total variation in resting QTc in EA individuals and ~12% to 18% in AA individuals. The PGS significantly increased variation explained at most significance thresholds (P<0.001), with a trend toward increased variation explained at more stringent P value cut points in the CAMP EA cohort (P<0.05). In AA individuals, PGS provided no improvement in variation explained at any significance threshold. CONCLUSIONS: For individuals of European descent, PGS provided a significant increase in variation in QT interval explained compared with a model with only nongenetic factors at nearly every significance level. There was no apparent benefit gained by relaxing the significance threshold from conventional genome-wide significance (P<5*10-8). PMID- 28986453 TI - Reduced Cardiac Calcineurin Expression Mimics Long-Term Hypoxia-Induced Heart Defects in Drosophila. AB - BACKGROUND: Hypoxia is often associated with cardiopulmonary diseases, which represent some of the leading causes of mortality worldwide. Long-term hypoxia exposures, whether from disease or environmental condition, can cause cardiomyopathy and lead to heart failure. Indeed, hypoxia-induced heart failure is a hallmark feature of chronic mountain sickness in maladapted populations living at high altitude. In a previously established Drosophila heart model for long-term hypoxia exposure, we found that hypoxia caused heart dysfunction. Calcineurin is known to be critical in cardiac hypertrophy under normoxia, but its role in the heart under hypoxia is poorly understood. METHODS AND RESULTS: In the present study, we explore the function of calcineurin, a gene candidate we found downregulated in the Drosophila heart after lifetime and multigenerational hypoxia exposure. We examined the roles of 2 homologs of Calcineurin A, CanA14F, and Pp2B in the Drosophila cardiac response to long-term hypoxia. We found that knockdown of these calcineurin catalytic subunits caused cardiac restriction under normoxia that are further aggravated under hypoxia. Conversely, cardiac overexpression of Pp2B under hypoxia was lethal, suggesting that a hypertrophic signal in the presence of insufficient oxygen supply is deleterious. CONCLUSIONS: Our results suggest a key role for calcineurin in cardiac remodeling during long term hypoxia with implications for diseases of chronic hypoxia, and it likely contributes to mechanisms underlying these disease states. PMID- 28986456 TI - Biases in Genetic Association of Coronary Heart Disease Events May Be Less Likely Than Suspected: Here Is When to Check for Them. PMID- 28986455 TI - Genomic Triangulation and Coverage Analysis in Whole-Exome Sequencing-Based Molecular Autopsies. AB - BACKGROUND: WEMA (Whole-Exome Molecular Autopsy) and surveillance of cardiac channelopathy and cardiomyopathy genes represents the latest molecular autopsy for sudden death in the young (SDY). To date, the majority of WEMA has been performed on the SDY case only. METHODS AND RESULTS: We performed whole-exome sequencing and nucleotide-level coverage analysis on 28 SDY cases (18.4+/-7.8 years) and their parents to determine the inheritance patterns of ultrarare, nonsynonymous variants in 99 sudden death-susceptibility genes. Nonsynonymous variants were adjudicated using the American College of Medical Genetics guidelines. Overall, 17 sudden death-susceptibility gene variants were identified in 12 of 28 (43%) SDY cases. On the basis of the American College of Medical Genetics guidelines, 6 of 28 (21%) cases had a pathogenic or likely pathogenic nonsynonymous variant with 3 (50%) being de novo. Two nonsynonymous variants would not have been elevated to likely pathogenic status without knowing their de novo status. Whole-exome sequencing reached a read depth of 10* across 90% of nucleotides within sudden death-susceptibility genes in 100% of parental exomes from fresh blood draw, compared with only 82% of autopsy-sourced SDY exomes. CONCLUSIONS: An SDY-parent, trio-based WEMA may be an effective way of elucidating a monogenic cause of death and bringing clarity to otherwise ambiguous variants. If other studies confirm this relatively high rate of SDY cases stemming from de novo mutations, then the WEMA should become even more cost effective given that the decedent's first-degree relatives should only need minimal cardiological evaluation. In addition, autopsy-sourced DNA demonstrated strikingly lower whole-exome sequencing coverage than DNA from fresh blood draw. PMID- 28986457 TI - Genomic Triangulation in Sudden Unexplained Death in the Young: The Way to Go? PMID- 28986458 TI - Pathogenicity of Hypertrophic Cardiomyopathy Variants: A Path Forward Together. PMID- 28986459 TI - High Heart: A Role for Calcineurin Signaling in Hypoxia-Influenced Cardiac Growth. PMID- 28986460 TI - QT Interval Determinant: Mutations, Rare Variants, or Single-Nucleotide Polymorphisms? PMID- 28986461 TI - GFP-Mutant Human Tau Transgenic Mice Develop Tauopathy Following CNS Injections of Alzheimer's Brain-Derived Pathological Tau or Synthetic Mutant Human Tau Fibrils. AB - Neurodegenerative proteinopathies characterized by intracellular aggregates of tau proteins, termed tauopathies, include Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD) with tau pathology (FTLD-tau), and related disorders. Pathological tau proteins derived from human AD brains (AD tau) act as proteopathic seeds that initiate the templated aggregation of soluble tau upon intracerebral injection into tau transgenic (Tg) and wild-type mice, thereby modeling human tau pathology. In this study, we found that aged Tg mice of both sexes expressing human tau proteins harboring a pathogenic P301L MAPT mutation labeled with green fluorescent protein (T40PL-GFP Tg mouse line) exhibited hyperphosphorylated tau mislocalized to the somatodentritic domain of neurons, but these mice did not develop de novo insoluble tau aggregates, which are characteristic of human AD and related tauopathies. However, intracerebral injections of either T40PL preformed fibrils (PFFs) or AD-tau seeds into T40PL GFP mice induced abundant intraneuronal pathological inclusions of hyperphosphorylated T40PL-GFP. These injections of pathological tau resulted in the propagation of tau pathology from the injection site to neuroanatomically connected brain regions, and these tau inclusions consisted of both T40PL-GFP and WT endogenous mouse tau. Primary neurons cultured from the brains of neonatal T40PL-GFP mice provided an informative in vitro model for examining the uptake and localization of tau PFFs. These findings demonstrate the seeded aggregation of T40PL-GFP in vivo by synthetic PFFs and human AD-tau and the utility of this system to study the neuropathological spread of tau aggregates.SIGNIFICANCE STATEMENT The stereotypical spread of pathological tau protein aggregates have recently been attributed to the transmission of proteopathic seeds. Despite the extensive use of transgenic mouse models to investigate the propagation of tau pathology in vivo, details of the aggregation process such as the early seeding events leading to new tau pathology have remained elusive. This study validates the use of GFP-labeled tau expressed by neurons in vivo and in vitro as models for investigating mechanisms underlying the seeded transmission of tau pathology as well as tau-focused drug discovery to identify disease-modifying therapies for AD and related tauopathies. PMID- 28986462 TI - The Lateral Habenula and Its Input to the Rostromedial Tegmental Nucleus Mediates Outcome-Specific Conditioned Inhibition. AB - Animals can readily learn that stimuli predict the absence of specific appetitive outcomes; however, the neural substrates underlying such outcome-specific conditioned inhibition remain largely unexplored. Here, using female and male rats as subjects, we examined the involvement of the lateral habenula (LHb) and of its inputs onto the rostromedial tegmental nucleus (RMTg) in inhibitory learning. In these experiments, we used backward conditioning and contingency reversal to establish outcome-specific conditioned inhibitors for two distinct appetitive outcomes. Then, using the Pavlovian-instrumental transfer paradigm, we assessed the effects of manipulations of the LHb and the LHb-RMTg pathway on that inhibitory encoding. In control animals, we found that an outcome-specific conditioned inhibitor biased choice away from actions delivering that outcome and toward actions earning other outcomes. Importantly, this bias was abolished by both electrolytic lesions of the LHb and selective ablation of LHb neurons using Cre-dependent Caspase3 expression in Cre-expressing neurons projecting to the RMTg. This deficit was specific to conditioned inhibition; an excitatory predictor of a specific outcome-biased choice toward actions delivering the same outcome to a similar degree whether the LHb or the LHb-RMTg network was intact or not. LHb lesions also disrupted the ability of animals to inhibit previously encoded stimulus-outcome contingencies after their reversal, pointing to a critical role of the LHb and of its inputs onto the RMTg in outcome-specific conditioned inhibition in appetitive settings. These findings are consistent with the developing view that the LHb promotes a negative reward prediction error in Pavlovian conditioning.SIGNIFICANCE STATEMENT Stimuli that positively or negatively predict rewarding outcomes influence choice between actions that deliver those outcomes. Previous studies have found that a positive predictor of a specific outcome biases choice toward actions delivering that outcome. In contrast, a negative predictor of an outcome biases choice away from actions earning that outcome and toward other actions. Here we reveal that the lateral habenula is critical for negative predictors, but not positive predictors, to affect choice. Furthermore, these effects were found to require activation of lateral habenula inputs to the rostromedial tegmental nucleus. These results are consistent with the view that the lateral habenula establishes inhibitory relationships between stimuli and food outcomes and computes a negative prediction error in Pavlovian conditioning. PMID- 28986464 TI - A Role of Endogenous Progesterone in Stroke Cerebroprotection Revealed by the Neural-Specific Deletion of Its Intracellular Receptors. AB - Treatment with progesterone protects the male and female brain against damage after middle cerebral artery occlusion (MCAO). However, in both sexes, the brain contains significant amounts of endogenous progesterone. It is not known whether endogenously produced progesterone enhances the resistance of the brain to ischemic insult. Here, we used steroid profiling by gas chromatography-tandem mass spectrometry (GC-MS/MS) for exploring adaptive and sex-specific changes in brain levels of progesterone and its metabolites after MCAO. We show that, in the male mouse brain, progesterone is mainly metabolized via 5alpha-reduction leading to 5alpha-dihydroprogesterone (5alpha-DHP), also a progesterone receptor (PR) agonist ligand in neural cells, then to 3alpha,5alpha-tetrahydroprogesterone (3alpha,5alpha-THP). In the female mouse brain, levels of 5alpha-DHP and 3alpha,5alpha-THP are lower and levels of 20alpha-DHP are higher than in males. After MCAO, levels of progesterone and 5alpha-DHP are upregulated rapidly to pregnancy-like levels in the male but not in the female brain. To assess whether endogenous progesterone and 5alpha-DHP contribute to the resistance of neural cells to ischemic damage, we inactivated PR selectively in the CNS. Deletion of PR in the brain reduced its resistance to MCAO, resulting in increased infarct volumes and neurological deficits in both sexes. Importantly, endogenous PR ligands continue to protect the brain of aging mice. These results uncover the unexpected importance of endogenous progesterone and its metabolites in cerebroprotection. They also reveal that the female reproductive hormone progesterone is an endogenous cerebroprotective neurosteroid in both sexes.SIGNIFICANCE STATEMENT The brain responds to injury with protective signaling and has a remarkable capacity to protect itself. We show here that, in response to ischemic stroke, levels of progesterone and its neuroactive metabolite 5alpha-dihydroprogesterone are upregulated rapidly in the male mouse brain but not in the female brain. An important role of endogenous progesterone in cerebroprotection was demonstrated by the conditional inactivation of its receptor in neural cells. These results show the importance of endogenous progesterone, its metabolites, and neural progesterone receptors in acute cerebroprotection after stroke. This new concept could be exploited therapeutically by taking into account the progesterone status of patients and by supplementing and reinforcing endogenous progesterone signaling for attaining its full cerebroprotective potential. PMID- 28986463 TI - Hebbian Learning in a Random Network Captures Selectivity Properties of the Prefrontal Cortex. AB - Complex cognitive behaviors, such as context-switching and rule-following, are thought to be supported by the prefrontal cortex (PFC). Neural activity in the PFC must thus be specialized to specific tasks while retaining flexibility. Nonlinear "mixed" selectivity is an important neurophysiological trait for enabling complex and context-dependent behaviors. Here we investigate (1) the extent to which the PFC exhibits computationally relevant properties, such as mixed selectivity, and (2) how such properties could arise via circuit mechanisms. We show that PFC cells recorded from male and female rhesus macaques during a complex task show a moderate level of specialization and structure that is not replicated by a model wherein cells receive random feedforward inputs. While random connectivity can be effective at generating mixed selectivity, the data show significantly more mixed selectivity than predicted by a model with otherwise matched parameters. A simple Hebbian learning rule applied to the random connectivity, however, increases mixed selectivity and enables the model to match the data more accurately. To explain how learning achieves this, we provide analysis along with a clear geometric interpretation of the impact of learning on selectivity. After learning, the model also matches the data on measures of noise, response density, clustering, and the distribution of selectivities. Of two styles of Hebbian learning tested, the simpler and more biologically plausible option better matches the data. These modeling results provide clues about how neural properties important for cognition can arise in a circuit and make clear experimental predictions regarding how various measures of selectivity would evolve during animal training.SIGNIFICANCE STATEMENT The prefrontal cortex is a brain region believed to support the ability of animals to engage in complex behavior. How neurons in this area respond to stimuli-and in particular, to combinations of stimuli ("mixed selectivity")-is a topic of interest. Even though models with random feedforward connectivity are capable of creating computationally relevant mixed selectivity, such a model does not match the levels of mixed selectivity seen in the data analyzed in this study. Adding simple Hebbian learning to the model increases mixed selectivity to the correct level and makes the model match the data on several other relevant measures. This study thus offers predictions on how mixed selectivity and other properties evolve with training. PMID- 28986465 TI - Dendritic and Axonal L-Type Calcium Channels Cooperate to Enhance Motoneuron Firing Output during Drosophila Larval Locomotion. AB - Behaviorally adequate neuronal firing patterns are critically dependent on the specific types of ion channel expressed and on their subcellular localization. This study combines in situ electrophysiology with genetic and pharmacological intervention in larval Drosophila melanogaster of both sexes to address localization and function of L-type like calcium channels in motoneurons. We demonstrate that Dmca1D (Cav1 homolog) L-type like calcium channels localize to both the somatodendritic and the axonal compartment of larval crawling motoneurons. In situ patch-clamp recordings in genetic mosaics reveal that Dmca1D channels increase burst duration and maximum intraburst firing frequencies during crawling-like motor patterns in semi-intact animals. Genetic and acute pharmacological manipulations suggest that prolonged burst durations are caused by dendritically localized Dmca1D channels, which activate upon cholinergic synaptic input and amplify EPSPs, thus indicating a conserved function of dendritic L-type channels from Drosophila to vertebrates. By contrast, maximum intraburst firing rates require axonal calcium influx through Dmca1D channels, likely to enhance sodium channel de-inactivation via a fast afterhyperpolarization through BK channel activation. Therefore, in unmyelinated Drosophila motoneurons different functions of axonal and dendritic L-type like calcium channels likely operate synergistically to maximize firing output during locomotion.SIGNIFICANCE STATEMENT Nervous system function depends on the specific excitabilities of different types of neurons. Excitability is largely shaped by different combinations of voltage-dependent ion channels. Despite a high degree of conservation, the huge diversity of ion channel types and their differential localization pose challenges in assigning distinct functions to specific channels across species. We find a conserved role, from fruit flies to mammals, for L-type calcium channels in augmenting motoneuron excitability. As in spinal cord, dendritic L-type channels amplify excitatory synaptic input. In contrast to spinal motoneurons, axonal L-type channels enhance firing rates in unmyelinated Drosophila motoraxons. Therefore, enhancing motoneuron excitability by L-type channels seems an old strategy, but localization and interactions with other channels are tuned to species-specific requirements. PMID- 28986468 TI - Intravenous alteplase and endovascular clot retrieval following reversal of dabigatran with idarucizumab. PMID- 28986469 TI - Staging of cortical and deep grey matter functional connectivity changes in multiple sclerosis. AB - OBJECTIVE: Functional connectivity is known to increase as well as decrease throughout the brain in multiple sclerosis (MS), which could represent different stages of the disease. In addition, functional connectivity changes could follow the atrophy pattern observed with disease progression, that is, moving from the deep grey matter towards the cortex. This study investigated when and where connectivity changes develop and explored their clinical and cognitive relevance across different MS stages. METHODS: A cohort of 121 patients with early relapsing-remitting MS (RRMS), 122 with late RRMS and 53 with secondary progressive MS (SPMS) as well as 96 healthy controls underwent MRI and neuropsychological testing. Functional connectivity changes were investigated for (1) within deep grey matter connectivity, (2) connectivity between the deep grey matter and cortex and (3) within-cortex connectivity. A post hoc regional analysis was performed to identify which regions were driving the connectivity changes. RESULTS: Patients with late RRMS and SPMS showed increased connectivity of the deep grey matter, especially of the putamen and palladium, with other deep grey matter structures and with the cortex. Within-cortex connectivity was decreased, especially for temporal, occipital and frontal regions, but only in SPMS relative to early RRMS. Deep grey matter connectivity alterations were related to cognition and disability, whereas within-cortex connectivity was only related to disability. CONCLUSION: Increased connectivity of the deep grey matter became apparent in late RRMS and further increased in SPMS. The additive effect of cortical network degeneration, which was only seen in SPMS, may explain the sudden clinical deterioration characteristic to this phase of the disease. PMID- 28986467 TI - Baseline prevalence and longitudinal evolution of non-motor symptoms in early Parkinson's disease: the PPMI cohort. AB - OBJECTIVE: To examine the baseline prevalence and longitudinal evolution in non motor symptoms (NMS) in a prospective cohort of, at baseline, patients with de novo Parkinson's disease (PD) compared with healthy controls (HC). METHODS: Parkinson's Progression Markers Initiative (PPMI) is a longitudinal, ongoing, controlled study of de novo PD participants and HC. NMS were rated using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part I score and other validated NMS scales at baseline and after 2 years. Biological variables included cerebrospinal fluid (CSF) markers and dopamine transporter imaging. RESULTS: 423 PD subjects and 196 HC were enrolled and followed for 2 years. MDS-UPDRS Part I total mean (SD) scores increased from baseline 5.6 (4.1) to 7.7 (5.0) at year 2 in PD subjects (p<0.001) versus from 2.9 (3.0) to 3.2 (3.0) in HC (p=0.38), with a significant difference between the groups (p<0.001). In the multivariate analysis, higher baseline NMS score was associated with female sex (p=0.008), higher baseline MDS-UPDRS Part II scores (p<0.001) and more severe motor phenotype (p=0.007). Longitudinal increase in NMS severity was associated with the older age (0.008) and lower CSF Abeta1-42 (0.005) at baseline. There was no association with the dose or class of dopaminergic therapy. CONCLUSIONS: This study of NMS in early PD identified clinical and biological variables associated with both baseline burden and predictors of progression. The association of a greater longitudinal increase in NMS with lower baseline Abeta1-42 level is an important finding that will have to be replicated in other cohorts. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01141023. PMID- 28986471 TI - International multicentre validation of the arteriovenous malformation-related intracerebral haemorrhage (AVICH) score. AB - OBJECTIVE: The recently published arteriovenous malformation-related intracerebral haemorrhage (AVICH) score showed better outcome prediction for patients with arteriovenous malformation (AVM)-related intracerebral haemorrhage (ICH) than other AVM or ICH scores. Here we present the results of a multicentre, external validation of the AVICH score. METHODS: All participating centres (n=11) provided anonymous data on 325 patients to form the Spetzler-Martin (SM) grade, the supplemented SM (sSM) grade, the ICH score and the AVICH score. Modified Rankin score (mRS) at last follow-up (mean 25.6 months) was dichotomized into favourable (mRS 0-2, n=210) and unfavourable (mRS 3-6;n=115). Univariate and AUROC analyses were performed to validate the AVICH score. RESULTS: Except nidus structure and AVM size, all single parameters forming the SM, sSM, ICH and AVICH score and the scores itself were significantly different between both outcome groups in the univariate analysis. The AVICH score was confirmed to be the highest predictive outcome score with an AUROC of 0.765 compared with 0.705 for the ICH score and 0.682 for the sSM grade. CONCLUSION: The multicentre-validated AVICH score predicts clinical outcome superior to pre-existing scores. We suggest the routine use of this score for future clinical outcome prediction and in clinical research. TRIAL REGISTRATION NUMBER: NCT02920645. PMID- 28986470 TI - Quality of life in inflammatory neuropathies: the IN-QoL. AB - BACKGROUND: No consensus exists which quality of life (QoL) measure should be used in patients with inflammatory neuropathies. Moreover, most QoL measures are ordinal-based scales with their known deficiencies. OBJECTIVES: To establish a new disease-specific interval-based QoL questionnaire in inflammatory neuropathies (IN-QoL) using the Rasch model and evaluate its scientific properties (validity, reliability and responsiveness). METHODS: 264 patients with inflammatory neuropathies completed six commonly used QoL questionnaires. The obtained data were stacked and subjected to Rasch analysis. Responsiveness was determined by using the concept of minimum clinically important differences related to varying individually obtained SEs (responsiveness definition: MCID SE>=1.96 after 1-year follow-up compared with baseline). RESULTS: The IN-QoL fulfilled all Rasch's model requirements with high internal reliability values (patient separation index of 0.94), except being multidimensional. Additional factor analysis resulted in two (functional and mental) subsets that were unidimensional on their own. The IN-QoL showed good correlation with the EuroQol health quality visual analogue scale (EQ-VAS) (Spearman's rho 0.72). It demonstrated acceptable responsiveness in patients with Guillain-Barre syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), as did the EQ-VAS. In patients with monoclonal gammopathy-related neuropathy and multifocal motor neuropathy, hardly any changes were seen over time. CONCLUSION: The IN-QoL questionnaire fulfils modern clinimetric requirements and correlates strongly with a patient's self-assessment of their own quality of health, while also showing responsiveness in patients with GBS and CIDP. We propose using the IN-QoL and the EQ-VAS for assessing the QoL of patients with inflammatory neuropathies in future studies. PMID- 28986472 TI - Flortaucipir tau PET imaging in semantic variant primary progressive aphasia. AB - OBJECTIVE: The semantic variant of primary progressive aphasia (svPPA) is typically associated with frontotemporal lobar degeneration (FTLD) with longTAR DNA-binding protein (TDP)-43-positive neuropil threads and dystrophic neurites (type C), and is only rarely due to a primary tauopathy or Alzheimer's disease. We undertook this study to investigate the localisation and magnitude of the presumed tau Positron Emission Tomography (PET) tracer [18F]Flortaucipir (FTP; also known as T807 or AV1451) in patients with svPPA, hypothesising that most patients would not show tracer uptake different from controls. METHODS: FTP and [11C]Pittsburgh compound B PET imaging as well as MRI were performed in seven patients with svPPA and in 20 controls. FTP signal was analysed by visual inspection and by quantitative comparison to controls, with and without partial volume correction. RESULTS: All seven patients showed elevated FTP uptake in the anterior temporal lobe with a leftward asymmetry that was not observed in healthy controls. This elevated FTP signal, largely co-localised with atrophy, was evident on both visual inspection and quantitative cortical surface-based analysis. Five patients were amyloid negative, one was amyloid positive and one has an unknown amyloid status. CONCLUSIONS: In this series of patients with clinical profiles, structural MRI and amyloid PET imaging typical for svPPA, FTP signal was unexpectedly elevated with a spatial pattern localised to areas of atrophy. This raises questions about the possible off-target binding of this tracer to non-tau molecules associated with neurodegeneration. Further investigation with autopsy analysis will help illuminate the binding target(s) of FTP in cases of suspected FTLD-TDP neuropathology. PMID- 28986473 TI - Mouse Red Blood Cell-Mediated Rare Xenobiotic Phosphorylation of a Drug Molecule Not Intended to Be a Kinase Substrate. AB - Phosphorylation of xenobiotics is rare, probably owing to a strong evolutionary pressure against it. This rarity may have attracted more attention recently as a result of intentionally designed kinase-substrate analogs that depend on kinase catalyzed activation to form phosphorylated active drugs. We report a rare phosphorylated metabolite observed unexpectedly in mouse plasma samples after an oral dose of a Tankyrase inhibitor that was not intended to be a kinase substrate, i.e., (S)-2-(4-(6-(3,4-dimethylpiperazin-1-yl)-4-methylpyridin-3 yl)phenyl)-8-(hydroxymethyl)quinazolin-4(3H)-one (AZ2381). The phosphorylated metabolite was not generated in mouse hepatocytes. In vitro experiments showed that the phosphorylation of AZ2381 occurred in mouse whole blood with heparin as anticoagulant but not in mouse plasma. The phosphorylated metabolite was also produced in rat, dog, and human blood, albeit at lower yields than in mouse. Divalent metal ions are required for the phosphorylation since the reaction is inhibited by the metal chelator EDTA. Further investigations with different cellular fractions of mouse blood revealed that the phosphorylation of AZ2381 was mediated by erythrocytes but did not occur with leukocytes. The levels of 18O incorporation into the phosphorylated metabolite when inorganic 18O4-phosphate and gamma-18O4-ATP were added to the mouse blood incubations separately suggested that the phosphoryl transfer was from inorganic phosphate rather than ATP. It remains unclear which enzyme present in red blood cells is responsible for this rare phosphorylation. PMID- 28986474 TI - Digging Deeper into CYP3A Testosterone Metabolism: Kinetic, Regioselectivity, and Stereoselectivity Differences between CYP3A4/5 and CYP3A7. AB - The metabolism of testosterone to 6beta-hydroxytestosterone (6beta-OH-T) is a commonly used assay to evaluate human CYP3A enzyme activities. However, previous reports have indicated that CYP3A7 also produces 2alpha-hydroxytestosterone (2alpha-OH-T) and that a 2alpha-OH-T/6beta-OH-T ratio may be a unique endogenous biomarker of the activity of the enzyme. Until now, the full metabolite and kinetic profile for testosterone hydroxylation by CYP3A7 has not been fully examined. To this end, we performed a complete kinetic analysis of the 6beta-OH T, 2alpha-OH-T, and 2beta-hydroxytestosterone metabolites for recombinant Supersome CYP3A4, CYP3A5, and CYP3A7 enzymes and monitored metabolism in fetal and adult human liver microsomes for comparison. In general, a decrease in the velocity of the reaction was observed between CYP3A4 and the two other enzymes, with CYP3A7 showing the lowest metabolic capacity. Interestingly, we found that the 2alpha-OH-T/6beta-OH-T ratio varied with substrate concentration when testosterone was incubated with CYP3A7, suggesting that this ratio would likely not function well as a biomarker for CYP3A7 activity. In silico docking studies revealed at least two different binding modes for testosterone between CYP3A4 and CYP3A7. In CYP3A4, the most energetically favorable docking mode places testosterone in a position with the methyl groups directed toward the heme iron, which is more favorable for oxidation at C6beta, whereas for CYP3A7 the testosterone methyl groups are positioned away from the heme, which is more favorable for an oxidation event at C2alpha In conclusion, our data indicate an alternative binding mode for testosterone in CYP3A7 that favors the 2alpha hydroxylation, suggesting significant structural differences in its active site compared with CYP3A4/5. PMID- 28986476 TI - Colistin is substrate of the carnitine/organic cation transporter 2 (OCTN2, SLC22A5). AB - Colistin is a polycation antibiotic used for the treatment of multidrug resistance (MDR) gram-negative infections; nevertheless, its use is often limited by the high incidence of renal damage. The mechanism underlying colistin-induced nephrotoxicity is not known, but perhaps related to its accumulation in the renal cortex upon extensive reabsorption from the nascent urine. Because little is known about the membrane transport of colistin, the purpose of the present study was to characterize better the transport system involved in colistin renal handling by using HEK293 cells stably transfected with the main organic cation transporters expressed at the apical membrane of the proximal tubule. [14C]Colistin was transported by the carnitine/organic cation transporter 2 (OCTN2, SLC22A5) but not by the organic cation transporter 1 (OCT1) and N1 (OCTN1). Non-labeled colistin inhibited the OCTN2-mediated transport of [3H]L carnitine in a non-competitive manner and that of [14C]tetraethylammonium bromide ([14C]TEA) in a competitive manner. Unlike that of [3H]L-carnitine, the [14C]colistin OCTN2-mediated uptake was Na+-independent. When endogenous OCTN2 mediated colistin transport was inhibited by co-incubation with L-carnitine, primary mouse proximal tubular cells were fully protected from colistin toxicity, suggesting that colistin toxicity occurred upon intracellular accumulation. PMID- 28986475 TI - Pediatric Cytochrome P450 Activity Alterations in Nonalcoholic Steatohepatitis. AB - Variable drug responses depend on individual variation in the activity of drug metabolizing enzymes, including cytochrome P450 enzymes (CYP). As the most common chronic liver disease in children and adults, nonalcoholic steatohepatitis (NASH) has been identified as a source of significant interindividual variation in hepatic drug metabolism. Compared with adults, children present age-related differences in pharmacokinetics and pharmacodynamics. The purpose of this study was to determine the impact of fatty liver disease severity on the activity of a variety of CYP enzymes in children and adolescents. Healthy and nonalcoholic fatty liver disease pediatric subjects aged 12-21 years inclusive received an oral cocktail of four probe drugs: caffeine (CYP1A2, 100 mg), omeprazole (CYP2C19, 20 mg), losartan (CYP2C9, 25 mg), and midazolam (CYP3A4, 2 mg). Venous blood and urine were collected before administration and 1, 2, 4, and 6 hours after administration. Concentrations of the parent drugs and CYP-specific metabolites were quantified in plasma and urine using liquid chromatography with tandem mass spectrometry. In plasma, the decreased metabolic area under the curve (AUC) ratio, defined as the metabolite AUC to parent AUC, of omeprazole indicated significant decreases of CYP2C19 (P = 0.002) enzymatic activities in NASH adolescents, while the urine analyses did not show significant differences and were highly variable. A comparison between the present in vivo pediatric studies and a previous ex vivo study in adults indicates distinct differences in the activities of CYP1A2 and CYP2C9. These data demonstrate that pediatric NASH presents an altered pattern of CYP activity and NASH should be considered as a confounder of drug metabolism for certain CYP enzymes. These differences could lead to future investigations that may reveal unexpected variable drug responses that should be considered in pediatric dosage recommendations. PMID- 28986478 TI - Charities 'thrilled' as animal cruelty sentencing set to increase tenfold. PMID- 28986483 TI - National equine survey uncovers common conditions. PMID- 28986479 TI - CSI Surrey: new integrated forensics venture launched. PMID- 28986486 TI - Disease surveillance in England and Wales, September 2017. AB - Current and emerging issues: Schmallenberg virusHighlights from the scanning surveillance networkon international disease threats Salmonella investigations in ruminants These are among matters discussed in the Animal and Plant Health Agency's (APHA's) disease surveillance report for September 2017. PMID- 28986487 TI - Salmonella investigations in ruminants. AB - Trigger factors for Salmonella infections Salmonella Typhimurium DT104 updateControl measures for Salmonella in livestockPublic health considerations These issues are considered in this month's surveillance focus article, which has been prepared by Gareth Hateley, veterinary lead of the Cattle Expert Group, and Amanda Carson, veterinary lead of the Small Ruminant Expert Group, of the APHA Surveillance Intelligence Unit. PMID- 28986488 TI - Neurological disease in ruminants. PMID- 28986489 TI - Ritual religious slaughter in the UK. PMID- 28986490 TI - Unusual presentation of myxomatosis. PMID- 28986491 TI - Worms at the Royal Welsh Show. PMID- 28986492 TI - Peer review. PMID- 28986493 TI - Canine demodicosis treatment survey. PMID- 28986494 TI - Thomas Wilson Groves. AB - Tom was a kind, gentle and knowledgeable man who lived a long and interesting life. PMID- 28986495 TI - Team Vet: working together. AB - John Fishwick, BVA's new President, introduces the theme he has chosen for his presidential year. PMID- 28986496 TI - Designer pets discussed in House of Lords. AB - Amy Waddell, BVA head of media and public affairs, outlines the current debate around animal welfare and 'designer' breeds in the House of Lords. PMID- 28986497 TI - BVA Policy Committee welcomes a new member. AB - Amelia Findon, BVA head of policy, introduces Sally Everitt, the newest member of the BVA Policy Committee. PMID- 28986498 TI - Mental health and the veterinary profession. AB - Ellie Patterson, Vetlife marketing officer, summarises the services offered by Vetlife - an independent, confidential and free charity for everyone in the veterinary community. PMID- 28986499 TI - Making rural Young Vet Network events a success. AB - Becky Richardson, Young Vet Network representative on BVA Council, discusses the anxieties and joys of hosting a rural YVN event. PMID- 28986500 TI - Surveillance in Scotland and Northern Ireland - how do you engage? AB - Hayley Atkin, BVA policy officer, encourages vets in Scotland and Northern Ireland to help BVA understand how they engage with veterinary surveillance. PMID- 28986503 TI - Working on the wild side. AB - With a final goal of working with wildlife, Justine Shotton built her career on travel, experiences and making the most of opportunities. PMID- 28986504 TI - Causes of Death in a Contemporary Cohort of Patients With Type 2 Diabetes and Atherosclerotic Cardiovascular Disease: Insights From the TECOS Trial. AB - OBJECTIVE: We evaluated the specific causes of death and their associated risk factors in a contemporary cohort of patients with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD). RESEARCH DESIGN AND METHODS: We used data from the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) study (n = 14,671), a cardiovascular (CV) safety trial adding sitagliptin versus placebo to usual care in patients with type 2 diabetes and ASCVD (median follow-up 3 years). An independent committee blinded to treatment assignment adjudicated each cause of death. Cox proportional hazards models were used to identify risk factors associated with each outcome. RESULTS: A total of 1,084 deaths were adjudicated as the following: 530 CV (1.2/100 patient-years [PY], 49% of deaths), 338 non-CV (0.77/100 PY, 31% of deaths), and 216 unknown (0.49/100 PY, 20% of deaths). The most common CV death was sudden death (n = 145, 27% of CV death) followed by acute myocardial infarction (MI)/stroke (n = 113 [MI n = 48, stroke n = 65], 21% of CV death) and heart failure (HF) (n = 63, 12% of CV death). The most common non-CV death was malignancy (n = 154, 46% of non-CV death). The risk of specific CV death subcategories was lower among patients with no baseline history of HF, including sudden death (hazard ratio [HR] 0.4; P = 0.0036), MI/stroke death (HR 0.47; P = 0.049), and HF death (HR 0.29; P = 0.0057). CONCLUSIONS: In this analysis of a contemporary cohort of patients with diabetes and ASCVD, sudden death was the most common subcategory of CV death. HF prevention may represent an avenue to reduce the risk of specific CV death subcategories. PMID- 28986505 TI - Associations Between Diabetes and Both Cardiovascular Disease and All-Cause Mortality Are Modified by Grip Strength: Evidence From UK Biobank, a Prospective Population-Based Cohort Study. AB - OBJECTIVE: Grip strength and diabetes are predictors of mortality and cardiovascular disease (CVD), but whether these risk factors interact to predispose to adverse health outcomes is unknown. This study determined the interactions between diabetes and grip strength and their association with health outcomes. RESEARCH DESIGN AND METHODS: We undertook a prospective, general population cohort study by using UK Biobank. Cox proportional hazards models were used to explore the associations between both grip strength and diabetes and the outcomes of all-cause mortality and CVD incidence/mortality as well as to test for interactions between diabetes and grip strength. RESULTS: A total of 347,130 UK Biobank participants with full data available (mean age 55.9 years, BMI 27.2 kg/m2, 54.2% women) were included in the analysis, of which 13,373 (4.0%) had diabetes. Over a median follow-up of 4.9 years (range 3.3-7.8 years), 6,209 died (594 as a result of CVD), and 4,301 developed CVD. Participants with diabetes were at higher risk of all-cause and CVD mortality and CVD incidence. Significant interactions (P < 0.05) existed whereby the risk of CVD mortality was higher in participants with diabetes with low (hazard ratio [HR] 4.05 [95% CI 2.72, 5.80]) versus high (HR 1.46 [0.87, 2.46]) grip strength. Similar results were observed for all-cause mortality and CVD incidence. CONCLUSIONS: Risk of adverse health outcomes among people with diabetes is lower in those with high grip strength. Low grip strength may be useful to identify a higher-risk subgroup of patients with diabetes. Intervention studies are required to determine whether resistance exercise can reduce risk. PMID- 28986507 TI - A conserved mammalian mitochondrial isoform of acetyl-CoA carboxylase ACC1 provides the malonyl-CoA essential for mitochondrial biogenesis in tandem with ACSF3. AB - Mitochondrial fatty acid synthesis (mtFAS) is a highly conserved pathway essential for mitochondrial biogenesis. The mtFAS process is required for mitochondrial respiratory chain assembly and function, synthesis of the lipoic acid cofactor indispensable for the function of several mitochondrial enzyme complexes and essential for embryonic development in mice. Mutations in human mtFAS have been reported to lead to neurodegenerative disease. The source of malonyl-CoA for mtFAS in mammals has remained unclear. We report the identification of a conserved vertebrate mitochondrial isoform of ACC1 expressed from an ACACA transcript splicing variant. A specific knockdown (KD) of the corresponding transcript in mouse cells, or CRISPR/Cas9-mediated inactivation of the putative mitochondrial targeting sequence in human cells, leads to decreased lipoylation and mitochondrial fragmentation. Simultaneous KD of ACSF3, encoding a mitochondrial malonyl-CoA synthetase previously implicated in the mtFAS process, resulted in almost complete ablation of protein lipoylation, indicating that these enzymes have a redundant function in mtFAS. The discovery of a mitochondrial isoform of ACC1 required for lipoic acid synthesis has intriguing consequences for our understanding of mitochondrial disorders, metabolic regulation of mitochondrial biogenesis and cancer. PMID- 28986506 TI - Sbp1 modulates the translation of Pab1 mRNA in a poly(A)- and RGG-dependent manner. AB - RNA-binding protein Sbp1 facilitates the decapping pathway in mRNA metabolism and inhibits global mRNA translation by an unclear mechanism. Here we report molecular interactions responsible for Sbp1-mediated translation inhibition of mRNA encoding the polyadenosine-binding protein (Pab1), an essential translation factor that stimulates mRNA translation and inhibits mRNA decapping in eukaryotic cells. We demonstrate that the two distal RRMs of Sbp1 bind to the poly(A) sequence in the 5'UTR of the Pab1 mRNA specifically and cooperatively while the central RGG domain of the protein interacts directly with Pab1. Furthermore, methylation of arginines in the RGG domain abolishes the protein-protein interaction and the inhibitory effect of Sbp1 on translation initiation of Pab1 mRNA. Based on these results, the underlying mechanism for Sbp1-specific translational regulation is proposed. The functional differences of Sbp1 and RGG repeats alone on transcript-specific translation were observed, and a comparison of the results suggests the importance of remodeling the 5'UTR by RNA-binding proteins in mRNA translation. PMID- 28986508 TI - Macromolecular assemblies of complex polysaccharides with galectin-3 and their synergistic effects on function. AB - Although pectin-derived polysaccharides can antagonize galectin function in various pathological disorders, the nature of their binding interactions needs to be better defined for developing them as drugs. Moreover, given their relatively large size and complexity, pectin-derived polysaccharides are also useful as model systems to assess inter-polysaccharide and protein-polysaccharide interactions. Here, we investigated interactions between galectin-3 (Gal-3) and pectin-derived polysaccharides: a rhamnogalacturonan (RG) and two homogalacturonans (HGs). BioLayer Interferometry and fluorescence-linked immunosorbent assays indicate that these polysaccharides bind Gal-3 with macroscopic or apparent KD values of 49 nM, 46 uM, and 138 uM, respectively. 15N 1H heteronuclear single quantum coherence (HSQC) NMR studies reveal that these polysaccharides interact primarily with the F-face of the Gal-3 carbohydrate recognition domain. Even though their binding to Gal-3 does not inhibit Gal-3 mediated T-cell apoptosis and only weakly attenuates hemagglutination, their combination in specific proportions increases activity synergistically along with avidity for Gal-3. This suggests that RG and HG polysaccharides act in concert, a proposal supported by polysaccharide particle size measurements and 13C-1H HSQC data. Our model has HG interacting with RG to promote increased avidity of RG for Gal-3, likely by exposing additional lectin-binding sites on the RG. Overall, the present study contributes to our understanding of how complex HG and RG polysaccharides interact with Gal-3. PMID- 28986509 TI - Why Targeting PSMA Is a Game Changer in the Management of Prostate Cancer. AB - Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein that is highly expressed on prostate adenocarcinomas, exhibits only limited expression in benign and extraprostatic tissues, and thus represents an ideal target for the diagnosis and management of prostate cancer. Since its discovery over 30 y ago, significant effort has been made to develop clinical technology targeting PSMA. The last 5 y have seen an explosion of development of new agents targeting PSMA for diagnostic and therapeutic use. Imaging agents targeting PSMA have been developed for SPECT and PET platforms. PSMA PET imaging appears to outperform traditional imaging in the high-risk localized-disease state, in patients with biochemical recurrence after treatment, and in advanced disease. To date, most of the reported clinical studies of therapeutic agents have used PSMA-targeted radiometals to deliver beta-radiation to metastatic disease sites, with 177Lu being the most widely investigated therapeutic radioisotope. Studies of both antibodies and small-molecule agents have been published and have demonstrated encouraging results. Safety appears generally limited to mild transient bone marrow toxicity and xerostomia because of uptake of the small-molecule agents in the salivary glands. Radiologic responses can be dramatic, and decreases in pain have been observed. The effect on overall survival, however, has yet to be demonstrated. PMID- 28986510 TI - Combined 18F-Fluciclovine PET/MRI Shows Potential for Detection and Characterization of High-Risk Prostate Cancer. AB - The objective of this study was to investigate whether quantitative imaging features derived from combined 18F-fluciclovine PET/multiparametric MRI show potential for detection and characterization of primary prostate cancer. Methods: Twenty-eight patients diagnosed with high-risk prostate cancer underwent simultaneous 18F-fluciclovine PET/MRI before radical prostatectomy. Volumes of interest (VOIs) for prostate tumors, benign prostatic hyperplasia (BPH) nodules, prostatitis, and healthy tissue were delineated on T2-weighted images, using histology as a reference. Tumor VOIs were marked as high-grade (>=Gleason grade group 3) or not. MRI and PET features were extracted on the voxel and VOI levels. Partial least-squared discriminant analysis (PLS-DA) with double leave-one patient-out cross-validation was performed to distinguish tumors from benign tissue (BPH, prostatitis, or healthy tissue) and high-grade tumors from other tissue (low-grade tumors or benign tissue). The performance levels of PET, MRI, and combined PET/MRI features were compared using the area under the receiver operating-characteristic curve (AUC). Results: Voxel and VOI features were extracted from 40 tumor VOIs (26 high-grade), 36 BPH VOIs, 6 prostatitis VOIs, and 37 healthy-tissue VOIs. PET/MRI performed better than MRI and PET alone for distinguishing tumors from benign tissue (AUCs of 87%, 81%, and 83%, respectively, at the voxel level and 96%, 93%, and 93%, respectively, at the VOI level) and high-grade tumors from other tissue (AUCs of 85%, 79%, and 81%, respectively, at the voxel level and 93%, 93%, and 91%, respectively, at the VOI level). T2-weighted MRI, diffusion-weighted MRI, and PET features were the most important for classification. Conclusion: Combined 18F-fluciclovine PET/multiparametric MRI shows potential for improving detection and characterization of high-risk prostate cancer, in comparison to MRI and PET alone. PMID- 28986511 TI - Neuroinflammation Appears Early on PET Imaging and Then Plateaus in a Mouse Model of Alzheimer Disease. AB - Neuroinflammation has been associated with various neurologic diseases, including Alzheimer disease (AD). In AD, the translocator protein 18 kDa (TSPO) is overexpressed in the activated microglia that surround the beta-amyloid plaques. In the current longitudinal study using a mouse model of AD, we evaluated the association between beta-amyloid deposition and neuroinflammation in AD. Methods: To monitor the longitudinal changes in beta-amyloid deposition and neuroinflammation, we used in vivo PET imaging and ex vivo autoradiography with Pittsburgh compound B (11C-PIB) and a TSPO tracer, flutriciclamide (18F-GE-180), in the APP23 mouse model of AD. We also applied immunohistochemistry to study beta-amyloid and activated microglia in the mouse brain tissue. Results: From 17 to 26 mo of age, the mice showed robust increased binding of 11C-PIB with aging in the frontal cortex, parietotemporal cortex, hippocampus, and thalamus whereas the increase in 18F-GE-180 binding with aging was minimal in areas of early amyloidosis such as the frontal cortex and hippocampus. A clear positive correlation between beta-amyloid deposition and neuroinflammation was detected with 11C-PIB and 18F-GE-180 only in the parietotemporal cortex and thalamus. Conclusion: The neuroinflammation increase detected with 18F-GE-180 is less than the increase in amyloidosis detected with 11C-PIB. Furthermore, binding of 18F-GE 180 plateaus at an earlier stage of pathogenesis whereas amyloidosis continues to increase. We suggest that TSPO can be a good marker for early pathogenesis detection but not for tracking long-term disease progression. PMID- 28986513 TI - Advantages and Limits of Targeted Radionuclide Therapy with Somatostatin Antagonists. PMID- 28986512 TI - Cold Kit for Prostate-Specific Membrane Antigen (PSMA) PET Imaging: Phase 1 Study of 68Ga-Tris(Hydroxypyridinone)-PSMA PET/CT in Patients with Prostate Cancer. AB - 68Ga-labeled urea-based inhibitors of the prostate-specific membrane antigen (PSMA), such as 68Ga-labeled N,N'-bis(2-hydroxybenzyl)ethylenediamine-N,N' diacetic acid (HBED)-PSMA-11, are promising small molecules for targeting prostate cancer. A new radiopharmaceutical, 68Ga-labeled tris(hydroxypyridinone) (THP)-PSMA, has a simplified design for single-step kit-based radiolabeling. It features the THP ligand, which forms complexes with 68Ga3+ rapidly at a low concentration, at room temperature, and over a wide pH range, enabling direct elution from a 68Ge/68Ga generator into a lyophilized radiopharmaceutical kit in 1 step without manipulation. The aim of this phase 1 study was to assess the safety and biodistribution of 68Ga-THP-PSMA. Methods: Cohort A comprised 8 patients who had proven prostate cancer and were scheduled to undergo prostatectomy; they had Gleason scores of 7-10 and a mean prostate-specific antigen level of 7.8 MUg/L (range, 5.4-10.6 MUg/L). They underwent PET/CT after the administration of 68Ga-THP-PSMA. All patients proceeded to prostatectomy (7 with pelvic nodal dissection). Dosimetry from multi-time-point PET imaging was performed with OLINDA/EXM. Cohort B comprised 6 patients who had positive 68Ga HBED-PSMA-11 PET/CT scanning results and underwent comparative 68Ga-THP-PSMA scanning. All patients were monitored for adverse events. Results: No adverse events occurred. In cohort A, 6 of 8 patients had focal uptake in the prostate (at 2 h: average SUVmax, 5.1; range, 2.4-9.2) and correlative 3+ staining of prostatectomy specimens on PSMA immunohistochemistry. The 2 68Ga-THP-PSMA scans with negative results had only 1+/2+ staining. The mean effective dose was 2.07E 02 mSv/MBq. In cohort B, 68Ga-THP-PSMA had lower physiologic background uptake than 68Ga-HBED-PSMA-11 (in the parotid glands, the mean SUVmax for 68Ga-THP-PSMA was 3.6 [compared with 19.2 for 68Ga-HBED-PSMA-11]; the respective corresponding values in the liver were 2.7 and 6.3, and those in the spleen were 2.7 and 10.5; P < 0.001 for all). In 5 of 6 patients, there was concordance in the number of metastases identified with 68Ga-HBED-PSMA-11 and 68Ga-THP-PSMA. Thirteen of 15 nodal abnormalities were subcentimeter. In 22 malignant lesions, the tumor-to liver contrast with 68Ga-THP-PSMA was similar to that with 68Ga-HBED-PSMA (4.7 and 5.4, respectively; P = 0.15), despite a higher SUVmax for 68Ga-HBED-PSMA than for 68Ga-THP-PSMA (30.3 and 10.7, respectively; P < 0.01). Conclusion:68Ga-THP PSMA is safe and has a favorable biodistribution for clinical imaging. Observed focal uptake in the prostate was localized to PSMA-expressing malignant tissue on histopathology. Metastatic PSMA-avid foci were also visualized with 68Ga-THP-PSMA PET. Single-step production from a Good Manufacturing Practice cold kit may enable rapid adoption. PMID- 28986514 TI - Nuclear Medicine Training in the United States. PMID- 28986515 TI - Improving admission medication reconciliation with pharmacists or pharmacy technicians in the emergency department: a randomised controlled trial. AB - BACKGROUND: Admission medication history (AMH) errors frequently cause medication order errors and patient harm. OBJECTIVE: To quantify AMH error reduction achieved when pharmacy staff obtain AMHs before admission medication orders (AMO) are placed. METHODS: This was a three-arm randomised controlled trial of 306 inpatients. In one intervention arm, pharmacists, and in the second intervention arm, pharmacy technicians, obtained initial AMHs prior to admission. They obtained and reconciled medication information from multiple sources. All arms, including the control arm, received usual AMH care, which included variation in several common processes. The primary outcome was severity-weighted mean AMH error score. To detect AMH errors, all patients received reference standard AMHs, which were compared with intervention and control group AMHs. AMH errors and resultant AMO errors were independently identified and rated by >=2 investigators as significant, serious or life threatening. Each error was assigned 1, 4 or 9 points, respectively, to calculate severity-weighted AMH and AMO error scores for each patient. RESULTS: Patient characteristics were similar across arms (mean+/ SD age 72+/-16 years, number of medications 15+/-7). Analysis was limited to 278 patients (91%) with reference standard AMHs. Mean+/-SD AMH errors per patient in the usual care, pharmacist and technician arms were 8.0+/-5.6, 1.4+/-1.9 and 1.5+/-2.1, respectively (p<0.0001). Mean+/-SD severity-weighted AMH error scores were 23.0+/-16.1, 4.1+/-6.8 and 4.1+/-7.0 per patient, respectively (p<0.0001). These AMH errors led to a mean+/-SD of 3.2+/-2.9, 0.6+/-1.1 and 0.6+/-1.1 AMO errors per patient, and mean severity-weighted AMO error scores of 6.9+/-7.2, 1.5+/-2.9 and 1.2+/-2.5 per patient, respectively (both p<0.0001). CONCLUSIONS: Pharmacists and technicians reduced AMH errors and resultant AMO errors by over 80%. Future research should examine other sites and patient-centred outcomes. TRIAL REGISTRATION NUMBER: NCT02026453. PMID- 28986516 TI - Mortality, readmission and length of stay have different relationships using hospital-level versus patient-level data: an example of the ecological fallacy affecting hospital performance indicators. AB - BACKGROUND: Ecological fallacy refers to an erroneous inference about individuals on the basis of findings for the group to which those individuals belong. Suppose analysis of a large database shows that hospitals with a high proportion of long length of stay (LOS) patients also have higher than average in-hospital mortality. This may prompt efforts to reduce mortality among patients with long LOS. But patients with long LOS may not be the ones at higher risk of death. It may be that hospitals with higher mortality (regardless of LOS) also have more long LOS patients-either because of quality problems on both counts or because of unaccounted differences in case mix. To provide more insight how the ecological fallacy influences the evaluation of hospital performance indicators, we assessed whether hospital-level associations between in-hospital mortality, readmission and long LOS reflect patient-level associations. METHODS: Patient admissions from the Dutch National Medical Registration (2007-2012) for specific diseases (stroke, colorectal carcinoma, heart failure, acute myocardial infarction and hip/knee replacements in patients with osteoarthritis) were analysed, as well as all admissions. Logistic regression analysis was used to assess patient-level associations. Pearson correlation coefficients were used to quantify hospital level associations. RESULTS: Overall, we observed 2.2% in-hospital mortality, 8.1% readmissions and a mean LOS of 5.9 days among 8 478 884 admissions in 95 hospitals. Of the 10 disease-specific associations tested, 2 were reversed at hospital-level, 3 were consistent and 5 were only significant at either hospital level or patient-level. A reversed association was found for stroke: patients with long LOS had 58% lower in-hospital mortality (OR 0.42 (95% CI 0.40 to 0.44)), whereas the hospital-level association was reversed (r=0.30, p<0.01). Similar negative patient-level associations were found for each hospital, but LOS varied across hospitals, thereby resulting in a positive hospital-level association. A similar effect was found for long LOS and readmission in patients with heart failure. CONCLUSIONS: Hospital-level associations did not reflect the same patient-level associations in 7 of 10 associations, and were even reversed in 2 associations. Ecological fallacy thus potentially influences interpretation of hospital performance when patient-level associations are not taken into account. PMID- 28986517 TI - Predictive Value of Circulating Tumor Cells for Evaluating Short- and Long-Term Efficacy of Chemotherapy for Breast Cancer. AB - BACKGROUND The present study investigated the role of circulating tumor cells (CTCs) counts in predicting the short- and long-term efficacy of chemotherapy for breast cancer (BC). MATERIAL AND METHODS Peripheral venous blood was extracted from 187 BC patients. CTCs were measured by flow cytometry. Spearman's correlation analysis was performed to examine the correlation between the efficacy of chemotherapy and CTC counts. A receiver operating characteristic (ROC) curve was plotted to estimate the predictive value of CTC counts. The Kaplan-Meier method was employed to calculate disease-free survival (DFS) and overall survival (OS). Cox regression analysis was used to determine risk factors for prognosis of BC. RESULTS Complete response (CR) + partial response (PR) was achieved by 65.8% of BC patients. After chemotherapy, CTC counts were decreased in both the CR + PR and SD + PD groups. Spearman's correlation analysis indicated that CTC counts before chemotherapy were positively correlated with clinical response to chemotherapy (r=0.45, P<0.05). For predicting clinical response to chemotherapy, CTC counts yielded an area under the curve (AUC) of 0.958, with sensitivity reaching 96.9% and specificity reaching 85.4%. The Kaplan-Meier method and Cox regression analysis indicated that tumor node metastasis (TNM) staging, lymph node metastasis (LNM), ki-67, endocrine therapy, and CTC counts were risk factors for prognosis of BC. CONCLUSIONS These findings indicate that BC patients with CTCs 38 exhibited poor response to chemotherapy and poor OS. CTC counts can serve as an indicator in predicting short- and long-term efficacy of chemotherapy for BC. PMID- 28986518 TI - Oxic-anoxic regime shifts mediated by feedbacks between biogeochemical processes and microbial community dynamics. AB - Although regime shifts are known from various ecosystems, the involvement of microbial communities is poorly understood. Here we show that gradual environmental changes induced by, for example, eutrophication or global warming can induce major oxic-anoxic regime shifts. We first investigate a mathematical model describing interactions between microbial communities and biogeochemical oxidation-reduction reactions. In response to gradual changes in oxygen influx, this model abruptly transitions between an oxic state dominated by cyanobacteria and an anoxic state with sulfate-reducing bacteria and phototrophic sulfur bacteria. The model predictions are consistent with observations from a seasonally stratified lake, which shows hysteresis in the transition between oxic and anoxic states with similar changes in microbial community composition. Our results suggest that hysteresis loops and tipping points are a common feature of oxic-anoxic transitions, causing rapid drops in oxygen levels that are not easily reversed, at scales ranging from small ponds to global oceanic anoxic events.The role of microbial communities in regime shifts is poorly understood. Here, the authors use a mathematical model and field data from a seasonally stratified lake to show that gradual environmental changes can induce oxic-anoxic regime shifts mediated by microbial community dynamics and redox processes. PMID- 28986519 TI - CRISPR/Cas9-induced transgene insertion and telomere-associated truncation of a single human chromosome for chromosome engineering in CHO and A9 cells. AB - Chromosome engineering techniques including gene insertion, telomere-associated truncation and microcell-mediated chromosome transfer (MMCT) are powerful tools for generation of humanised model animal, containing megabase-sized genomic fragments. However, these techniques require two cell lines: homologous recombination (HR)-proficient DT40 cells for chromosome modification, and CHO cells for transfer to recipient cells. Here we show an improved technique using a combination of CRISPR/Cas9-induced HR in CHO and mouse A9 cells without DT40 cells following MMCT to recipient cells. Transgene insertion was performed in CHO cells with the insertion of enhanced green fluorescence protein (EGFP) using CRISPR/Cas9 and a circular targeting vector containing two 3 kb HR arms. Telomere associated truncation was performed in CHO cells using CRISPR/Cas9 and a linearised truncation vector containing a single 7 kb HR arm at the 5' end, a 1 kb artificial telomere at the 3' end. At least 11% and 6% of the targeting efficiency were achieved for transgene insertion and telomere-associated truncation, respectively. The transgene insertion was also confirmed in A9 cells (29%). The modified chromosomes were transferrable to other cells. Thus, this CHO and A9 cell-mediated chromosome engineering using the CRISPR/Cas9 for direct transfer of the modified chromosome is a rapid technique that will facilitate chromosome manipulation. PMID- 28986520 TI - Regional variation in health is predominantly driven by lifestyle rather than genetics. AB - Regional differences in health-related phenotypes have been detected between and within countries. In Scotland, regions differ for a variety of health-related traits and display differences in mean lifespan of up to 7.5 years. Both genetics and lifestyle differences are potential causes of this variation. Using data on obesity-related traits of ~11,000 Scottish individuals with genome-wide genetic information and records of lifestyle and socioeconomic factors, we explored causes of regional variation by using models that incorporate genetic and environmental information jointly. We found that variation between individuals within regions showed substantial influence of both genetic variation and family environment. Regional variation for most obesity traits was associated with lifestyle and socioeconomic variables, such as smoking, diet and deprivation which are potentially modifiable. There was limited evidence that regional differences were of genetic origin. This has important implications for healthcare policies, suggesting that inequalities can be tackled with appropriate social and economic interventions.Health-related traits are known to vary geographically. Here, Amador and colleagues show that regional variation of obesity-related traits in a Scottish population is influenced more by lifestyle differences than it is by genetic differences. PMID- 28986521 TI - Conformal Vortex Crystals. AB - We investigate theoretically globally nonuniform configurations of quantized-flux vortices in clean superconductors trapped by an external force field that induces a nonuniform vortex density profile. Using an extensive series of numerical simulations, we demonstrate that, for suitable choices of the force field, and bellow a certain transition temperature, the vortex system self-organizes into highly inhomogeneous conformal crystals in a way as to minimize the total energy. These nonuniform structures are topologically ordered and can be mathematically mapped into a triangular Abrikosov lattice via a conformal transformation. Above the crystallization temperature, the conformal vortex crystal becomes unstable and gives place to a nonuniform polycrystalline structure. We propose a simple method to engineer the potential energy profile necessary for the observation of conformal crystals of vortices, which can also be applied to other 2D particle systems, and suggest possible experiments in which conformal or quasi-conformal vortex crystals could be observed in bulk superconductors and in thin films. PMID- 28986523 TI - Bagging Nearest-Neighbor Prediction independence Test: an efficient method for nonlinear dependence of two continuous variables. AB - Testing dependence/correlation of two variables is one of the fundamental tasks in statistics. In this work, we proposed an efficient method for nonlinear dependence of two continuous variables (X and Y). We addressed this research question by using BNNPT (Bagging Nearest-Neighbor Prediction independence Test, software available at https://sourceforge.net/projects/bnnpt/). In the BNNPT framework, we first used the value of X to construct a bagging neighborhood structure. We then obtained the out of bag estimator of Y based on the bagging neighborhood structure. The square error was calculated to measure how well Y is predicted by X. Finally, a permutation test was applied to determine the significance of the observed square error. To evaluate the strength of BNNPT compared to seven other methods, we performed extensive simulations to explore the relationship between various methods and compared the false positive rates and statistical power using both simulated and real datasets (Rugao longevity cohort mitochondrial DNA haplogroups and kidney cancer RNA-seq datasets). We concluded that BNNPT is an efficient computational approach to test nonlinear correlation in real world applications. PMID- 28986522 TI - Mammalian APE1 controls miRNA processing and its interactome is linked to cancer RNA metabolism. AB - Mammalian apurinic/apyrimidinic endonuclease 1 is a DNA repair enzyme involved in genome stability and expression of genes involved in oxidative stress responses, tumor progression and chemoresistance. However, the molecular mechanisms underlying the role of apurinic/apyrimidinic endonuclease 1 in these processes are still unclear. Recent findings point to a novel role of apurinic/apyrimidinic endonuclease 1 in RNA metabolism. Through the characterization of the interactomes of apurinic/apyrimidinic endonuclease 1 with RNA and other proteins, we demonstrate here a role for apurinic/apyrimidinic endonuclease 1 in pri-miRNA processing and stability via association with the DROSHA-processing complex during genotoxic stress. We also show that endonuclease activity of apurinic/apyrimidinic endonuclease 1 is required for the processing of miR 221/222 in regulating expression of the tumor suppressor PTEN. Analysis of a cohort of different cancers supports the relevance of our findings for tumor biology. We also show that apurinic/apyrimidinic endonuclease 1 participates in RNA-interactomes and protein-interactomes involved in cancer development, thus indicating an unsuspected post-transcriptional effect on cancer genes.APE1 plays an important role in the cellular response to oxidative stress, and mutations are linked to tumor progression and chemoresistance. Here, the authors characterize the interactions of APE1 with RNA and demonstrate a role in microRNA processing. PMID- 28986524 TI - Process reveals structure: How a network is traversed mediates expectations about its architecture. AB - Network science has emerged as a powerful tool through which we can study the higher-order architectural properties of the world around us. How human learners exploit this information remains an essential question. Here, we focus on the temporal constraints that govern such a process. Participants viewed a continuous sequence of images generated by three distinct walks on a modular network. Walks varied along two critical dimensions: their predictability and the density with which they sampled from communities of images. Learners exposed to walks that richly sampled from each community exhibited a sharp increase in processing time upon entry into a new community. This effect was eliminated in a highly regular walk that sampled exhaustively from images in short, successive cycles (i.e., that increasingly minimized uncertainty about the nature of upcoming stimuli). These results demonstrate that temporal organization plays an essential role in learners' sensitivity to the network architecture underlying sensory input. PMID- 28986526 TI - Broadband reconfigurable logic gates in phonon waveguides. AB - The high-quality-factor mechanical resonator in electromechanical systems has facilitated dynamic control of phonons via parametric nonlinear processes and paved the development of mechanical logic-elements. However, the narrow spectral bandwidth of the resonating element constrains the available nonlinear phenomena thus limiting the functionality of the device as well as the switching speeds. Here we have developed phonon waveguides, with a two-octave-wide phonon transmission band, in which mechanical four-wave-like mixing is demonstrated that enables the frequency of phonon waves to be converted over 1 MHz. We harness this platform to execute multiple binary mechanical logic gates in parallel, via frequency division multiplexing in this broadband, where each gate can be independently reconfigured. The fidelity of the binary gates is verified via temporal measurements yielding eye diagrams which confirm the availability of high speed logic operations. The phonon waveguide architecture thus offers the broadband functionality that is essential to realising mechanical signal processors. PMID- 28986525 TI - Non-invasive assessment of hepatic mitochondrial metabolism by positional isotopomer NMR tracer analysis (PINTA). AB - Hepatic mitochondria play a central role in the regulation of intermediary metabolism and maintenance of normoglycemia, and there is great interest in assessing rates of hepatic mitochondrial citrate synthase flux (V CS) and pyruvate carboxylase flux (V PC) in vivo. Here, we show that a positional isotopomer NMR tracer analysis (PINTA) method can be used to non-invasively assess rates of V CS and V PC fluxes using a combined NMR/gas chromatography-mass spectrometry analysis of plasma following infusion of [3-13C]lactate and glucose tracer. PINTA measures V CS and V PC fluxes over a wide range of physiological conditions with minimal pyruvate cycling and detects increased hepatic V CS following treatment with a liver-targeted mitochondrial uncoupler. Finally, validation studies in humans demonstrate that the V PC/V CS ratio measured by PINTA is similar to that determined by in vivo NMR spectroscopy. This method will provide investigators with a relatively simple tool to non-invasively examine the role of altered hepatic mitochondrial metabolism.Liver mitochondrial metabolism plays an important role for glucose and lipid homeostasis and its alterations contribute to metabolic disorders, including fatty liver and diabetes. Here Perry et al. develop a method for the measurement of hepatic fluxes by using lactate and glucose tracers in combination with NMR spectroscopy. PMID- 28986528 TI - Insensitive ionic bio-energetic materials derived from amino acids. AB - Energetic salts/ionic liquids have received increasing attention as fascinating energetic materials, and the use of renewable compounds is a promising approach to developing energetic materials. Until recently, biomolecules have been used as raw materials to develop neutral energetic compounds, whereas research focused on ionic energetic materials obtained from natural bio-renewable frameworks is scarce. This work systematically investigates ionic bio-energetic materials (IBEMs) derived from sustainable natural amino acids. In addition to combustibility, high density, good thermal stability, and one-step preparation, these IBEMs demonstrated apparent hypotoxicity and insensitivity. Moreover, a theoretical examination was performed to explore their appropriate properties. The intriguing results of this study indicates that IBEMs are potential bio-based energetic materials. PMID- 28986527 TI - Behavior of human periodontal ligament cells on dentin surfaces ablated with an ultra-short pulsed laser. AB - This study aimed to evaluate the effects of an ultrashort pulsed laser (USPL) (1064 nm, 20 ps, 100 kHz) with different laser fluences (F, 4, 6, 8 J/cm2) and pulse overlaps (PO, 0, 50%) on human periodontal ligament cells (hPDLs) behavior. Dentin samples were ablated with USPL with different combinations of fluences and pulse overlaps; some samples were ablated with an Er:YAG laser (2940 nm, 150 us, 100 mJ/pulse, 5 J/cm2) and some samples were ground with a carbide bur. Then hPDLs were grown on the samples after different treatments. Dentin morphology and cell adhesion were observed with SEM and gene expressions were measured by RT PCR. The results showed dentin surfaces ablated with USPL when F = 4 J/cm2, PO = 0, and F = 6 J/cm2, PO = 0 were partially intact with obvious ridges and valleys and cells on these surfaces grew mostly along the valleys. USPL ablated surfaces in other groups were entirely ablated and cell cluster formation was observed. The RT-PCR results showed an upregulation of osteocalcin of cells grown on the dentin after some laser treatment. It can be concluded that USPL could improve the attachment and differentiation of hPDLs and thus potentially promote periodontal tissue regeneration. PMID- 28986529 TI - Synthesis and characterization of emamectin-benzoate slow-release microspheres with different surfactants. AB - Pesticide slow-release formulations provide a way to increase the efficiency of active components by reducing the amount of pesticide that needs to be applied. Slow-release formulations also increase the stability and prolong the control effect of photosensitive pesticides. Surfactants are an indispensable part of pesticide formulations, and the choice of surfactant can strongly affect formulation performance. In this study, emamectin-benzoate (EMB) slow-release microspheres were prepared by the microemulsion polymerization method. We explored the effect of different surfactants on the particle size and dispersity of EMB in slow-release microspheres. The results indicated that the samples had uniform spherical shapes with an average diameter of 320.5 +/-5.24 nm and good dispersity in the optimal formulation with the polymeric stabilizer polyvinyl alcohol (PVA) and composite non-ionic surfactant polyoxyethylene castor oil (EL- 40). The optimal EMB pesticide slow-release microspheres had excellent anti photolysis performance, stability, controlled release properties, and good leaf distribution. These results demonstrated that EMB slow-release microspheres are an attractive candidate for improving pesticide efficacy and prolonging the control effect of EMB in the environment. PMID- 28986530 TI - Synchronized conductivity modulation to realize broadband lossless magnetic-free non-reciprocity. AB - Recent research has explored the spatiotemporal modulation of permittivity to break Lorentz reciprocity in a manner compatible with integrated-circuit fabrication. However, permittivity modulation is inherently weak and accompanied by loss due to carrier injection, particularly at higher frequencies, resulting in large insertion loss, size, and/or narrow operation bandwidths. Here, we show that the presence of absorption in an integrated electronic circuit may be counter-intuitively used to our advantage to realize a new generation of magnet free non-reciprocal components. We exploit the fact that conductivity in semiconductors provides a modulation index several orders of magnitude larger than permittivity. While directly associated with loss in static systems, we show that properly synchronized conductivity modulation enables loss-free, compact and extremely broadband non-reciprocity. We apply these concepts to obtain a wide range of responses, from isolation to gyration and circulation, and verify our findings by realizing a millimeter-wave (25 GHz) circulator fully integrated in complementary metal-oxide-semiconductor technology.Optical non-reciprocity achieved through refractive index modulation can have its challenges and limitations. Here, Dinc et al. introduce the concept of non-reciprocity based on synchronized spatio-temporal modulation of conductivity to achieve different types of non-reciprocal functionality. PMID- 28986531 TI - Experimental testing of reciprocal effects of nutrition and parasitism in wild black capuchin monkeys. AB - Nutritional stress may predispose individuals to infection, which in turn can have further detrimental effects on physical condition, thus creating an opportunity for reciprocal effects between nutrition and parasitism. Little experimental investigation has been conducted on this "vicious circle" hypothesis in wild animals, especially under natural conditions. We evaluated the reciprocal effects of nutritional status and parasitism using an experimental approach in two groups of wild black capuchin monkeys (Sapajus nigritus). Across two consecutive winters, we collected faecal samples from identified capuchins to determine presence and load of gastrointestinal helminthes, and measured individual body mass as a proxy of physical condition. Food availability was manipulated by provisioning monkeys with bananas, and parasite burdens by applying antiparasitic drugs to selected individuals. We found no effect of antiparasitic drugs on physical condition, but parasite loads decreased in response to high levels of food availability. Our results represent the first experimental evidence that the nutritional status may drive parasite dynamics in a primate. PMID- 28986532 TI - Predicting the effect of habitat modification on networks of interacting species. AB - A pressing challenge for ecologists is predicting how human-driven environmental changes will affect the complex pattern of interactions among species in a community. Weighted networks are an important tool for studying changes in interspecific interactions because they record interaction frequencies in addition to presence or absence at a field site. Here we show that changes in weighted network structure following habitat modification are, in principle, predictable. Our approach combines field data with mathematical models: the models separate changes in relative species abundance from changes in interaction preferences (which describe how interaction frequencies deviate from random encounters). The models with the best predictive ability compared to data requirement are those that capture systematic changes in interaction preferences between different habitat types. Our results suggest a viable approach for predicting the consequences of rapid environmental change for the structure of complex ecological networks, even in the absence of detailed, system-specific empirical data.In a changing world, the ability to predict the impact of environmental change on ecological communities is essential. Here, the authors show that by separating species abundances from interaction preferences, they can predict the effects of habitat modification on the structure of weighted species interaction networks, even with limited data. PMID- 28986533 TI - Generation of micro-droplet arrays by dip-coating of biphilic surfaces; the dependence of entrained droplet volume on withdrawal velocity. AB - Droplet array chips were realized using an alignment-free fabrication process in silicon. The chips were textured with a homogeneous nano-scale surface roughness but were partially covered with a self-assembled monolayer of perfluorodecyltrichlorosilane (FDTS), resulting in a super-biphilic surface. When submerged in water and withdrawn again, microliter sized droplets are formed due to pinning of water on the hydrophilic spots. The entrained droplet volumes were investigated under variation of spot size and withdrawal velocity. Two regimes of droplet formation were revealed: at low speeds, the droplet volume achieved finite values even for vanishing speeds, while at higher speeds the volume was governed by fluid inertia. A simple 2D boundary layer model describes the behavior at high speeds well. Entrained droplet volume could be altered, post fabrication, by more than a factor of 15, which opens up for more applications of the dip-coating technique due to the significant increase in versatility of the micro-droplet array platform. PMID- 28986534 TI - Spatial scale of receptive fields in the visual sector of the cat thalamic reticular nucleus. AB - Inhibitory projections from the visual sector of the thalamic reticular nucleus to the lateral geniculate nucleus complete the earliest feedback loop in the mammalian visual pathway and regulate the flow of information from retina to cortex. There are two competing hypotheses about the function of the thalamic reticular nucleus. One regards the structure as a thermostat that uniformly regulates thalamic activity through negative feedback. Alternatively, the searchlight hypothesis argues for a role in focal attentional modulation through positive feedback, consistent with observations that behavioral state influences reticular activity. Here, we address the question of whether cells in the reticular nucleus have receptive fields small enough to provide localized feedback by devising methods to quantify the size of these fields across visual space. Our results show that reticular neurons in the cat operate over discrete spatial scales, at once supporting the searchlight hypothesis and a role in feature selective sensory processing.The searchlight hypothesis proposes that the thalamic reticular nucleus regulates thalamic relay activity through focal attentional modulation. Here the authors show that the receptive field sizes of reticular neurons are small enough to provide localized feedback onto thalamic neurons in the visual pathway. PMID- 28986535 TI - An extinct vertebrate preserved by its living hybridogenetic descendant. AB - Hybridogenesis is a special mode of hybrid reproduction where one parental genome is eliminated and the other is transmitted clonally. We propose that this mechanism can perpetuate the genome of extinct species, based on new genetic data from Pelophylax water frogs. We characterized the genetic makeup of Italian hybridogenetic hybrids (P. kl. hispanicus and esculentus) and identified a new endemic lineage of Eastern-Mediterranean origin as one parental ancestor of P. kl. hispanicus. This taxon is nowadays extinct in the wild but its germline subsists through its hybridogenetic descendant, which can thus be considered as a "semi living fossil". Such rare situation calls for realistic efforts of de extinction through selective breeding without genetic engineering, and fuels the topical controversy of reviving long extinct species. "Ghost" species hidden by taxa of hybrid origin may be more frequent than suspected in vertebrate groups that experienced a strong history of hybridization and semi-sexual reproduction. PMID- 28986536 TI - Disordered Supersolids in the Extended Bose-Hubbard Model. AB - The extended Bose-Hubbard model captures the essential properties of a wide variety of physical systems including ultracold atoms and molecules in optical lattices, Josephson junction arrays, and certain narrow band superconductors. It exhibits a rich phase diagram including a supersolid phase where a lattice solid coexists with a superfluid. We use quantum Monte Carlo to study the supersolid part of the phase diagram of the extended Bose-Hubbard model on the simple cubic lattice. We add disorder to the extended Bose-Hubbard model and find that the maximum critical temperature for the supersolid phase tends to be suppressed by disorder. But we also find a narrow parameter window in which the supersolid critical temperature is enhanced by disorder. Our results show that supersolids survive a moderate amount of spatial disorder and thermal fluctuations in the simple cubic lattice. PMID- 28986537 TI - Counterbalancing anti-adhesive effects of Tenascin-C through fibronectin expression in endothelial cells. AB - Cellular fibronectin (FN) and tenascin-C (TNC) are prominent development- and disease-associated matrix components with pro- and anti-adhesive activity, respectively. Whereas both are present in the tumour vasculature, their functional interplay on vascular endothelial cells remains unclear. We have previously shown that basally-oriented deposition of a FN matrix restricts motility and promotes junctional stability in cultured endothelial cells and that this effect is tightly coupled to expression of FN. Here we report that TNC induces FN expression in endothelial cells. This effect counteracts the potent anti-adhesive activity of TNC and leads to the assembly of a dense highly branched subendothelial matrix that enhances tubulogenic activity. These findings suggest that pro-angiogenic remodelling of the perivascular matrix may involve TNC-induced upregulation of FN in endothelial cells. PMID- 28986538 TI - Circulating microRNAs: a novel potential biomarker for diagnosing acute aortic dissection. AB - Acute aortic dissection (AAD) is a catastrophic emergency with high mortality and misdiagnosis rate. We aimed to determine whether circulating microRNAs allow to distinguish AAD from healthy controls and chest pain patients without AAD (CP). Plasma microRNAs expression were determined in 103 participants, including 37 AAD patients, 26 chronic aortic dissection patients, 17 healthy volunteers, 23 patients without AAD. We selected 16 microRNAs from microarray screening as candidates for further testing via qRT-PCR. The results showed that plasma miR 15a in patients with AAD (n = 37) had significantly higher expression levels than it from control group (n = 40; P = 0.008). By receiver operating characteristic curve analysis, the sensitivity was 75.7%; the specificity was 82.5%; and the AUC was 0.761 for detection of AAD. Furthermore, 37 patients with AAD had significantly higher plasma expression levels of let-7b, miR-15a, miR-23a and hcmv-miR-US33-5p compared with 14 CP patients of 40 controls (P = 0.000, 0.000, 0.026 and 0.011, respectively). The corresponding sensitivity were 79.4%, 75.7%, 91.9% and 73.5%, respectively; the specificity were 92.9%, 100%, 85.7% and 85.7%, respectively; and the AUCs of these microRNAs were 0.887, 0.855, 0.925 and 0.815, respectively. These data indicate that plasma miR-15a and miR-23a have promising clinical value in diagnosing AAD. PMID- 28986539 TI - Enhancing robustness of interdependent network under recovery based on a two layer-protection strategy. AB - The robustness of coupled networks has attracted great attention recently, because the spread of failures from one network to its coupled network makes the coupled networks more vulnerable. Most existing achievements mainly focused on the integrity properties of coupled networks. However, failures also exist when networks are being reconstructed. Moreover, existing node-protection methods which aim to enhance the robustness of coupled networks only protect the influential nodes in one layer. In this paper, firstly, a two-layer-protection strategy is proposed to enhance the robustness of coupled networks under their reconstruction. Secondly, we adopt five strategies based on different centralities to select influential nodes, and propose a two-layer vision for each of them. Lastly, experiments on three different coupled networks show that by applying the two-layer-protection strategy, the robustness of coupled networks can be enhanced more efficiently compared with other methods which only protect nodes in one layer. PMID- 28986540 TI - Reactive metabolites of acetaminophen activate and sensitize the capsaicin receptor TRPV1. AB - The irritant receptor TRPA1 was suggested to mediate analgesic, antipyretic but also pro-inflammatory effects of the non-opioid analgesic acetaminophen, presumably due to channel activation by the reactive metabolites parabenzoquinone (pBQ) and N-acetyl-parabenzoquinonimine (NAPQI). Here we explored the effects of these metabolites on the capsaicin receptor TRPV1, another redox-sensitive ion channel expressed in sensory neurons. Both pBQ and NAPQI, but not acetaminophen irreversibly activated and sensitized recombinant human and rodent TRPV1 channels expressed in HEK 293 cells. The reducing agents dithiothreitol and N acetylcysteine abolished these effects when co-applied with the metabolites, and both pBQ and NAPQI failed to gate TRPV1 following substitution of the intracellular cysteines 158, 391 and 767. NAPQI evoked a TRPV1-dependent increase in intracellular calcium and a potentiation of heat-evoked currents in mouse spinal sensory neurons. Although TRPV1 is expressed in mouse hepatocytes, inhibition of TRPV1 did not alleviate acetaminophen-induced hepatotoxicity. Finally, intracutaneously applied NAPQI evoked burning pain and neurogenic inflammation in human volunteers. Our data demonstrate that pBQ and NAQPI activate and sensitize TRPV1 by interacting with intracellular cysteines. While TRPV1 does not seem to mediate acetaminophen-induced hepatotoxicity, our data identify TRPV1 as a target of acetaminophen with a potential relevance for acetaminophen-induced analgesia, antipyresia and inflammation. PMID- 28986541 TI - Cyclophilin D ablation is associated with increased end-ischemic mitochondrial hexokinase activity. AB - Both the absence of cyclophilin D (CypD) and the presence of mitochondrial bound hexokinase II (mtHKII) protect the heart against ischemia/reperfusion (I/R) injury. It is unknown whether CypD determines the amount of mtHKII in the heart. We examined whether CypD affects mtHK in normoxic, ischemic and preconditioned isolated mouse hearts. Wild type (WT) and CypD-/- mouse hearts were perfused with glucose only and subjected to 25 min ischemia and reperfusion. At baseline, cytosolic and mtHK was similar between hearts. CypD ablation protected against I/R injury and increased ischemic preconditioning (IPC) effects, without affecting end-ischemic mtHK. When hearts were perfused with glucose, glutamine, pyruvate and lactate, the preparation was more stable and CypD ablation-resulted in more protection that was associated with increased mtHK activity, leaving little room for additional protection by IPC. In conclusion, in glucose only perfused hearts, deletion of CypD is not associated with end-ischemic mitochondrial-HK binding. In contrast, in the physiologically more relevant multiple-substrate perfusion model, deletion of CypD is associated with an increased mtHK activity, possibly explaining the increased protection against I/R injury. PMID- 28986542 TI - Evidence of mixotrophic carbon-capture by n-butanol-producer Clostridium beijerinckii. AB - Recent efforts to combat increasing greenhouse gas emissions include their capture into advanced biofuels, such as butanol. Traditionally, biobutanol research has been centered solely on its generation from sugars. Our results show partial re-assimilation of CO2 and H2 by n-butanol-producer C. beijerinckii. This was detected as synchronous CO2/H2 oscillations by direct (real-time) monitoring of their fermentation gasses. Additional functional analysis demonstrated increased total carbon recovery above heterotrophic values associated to mixotrophic assimilation of synthesis gas (H2, CO2 and CO). This was further confirmed using 13C-Tracer experiments feeding 13CO2 and measuring the resulting labeled products. Genome- and transcriptome-wide analysis revealed transcription of key C-1 capture and additional energy conservation genes, including partial Wood-Ljungdahl and complete reversed pyruvate ferredoxin oxidoreductase / pyruvate-formate-lyase-dependent (rPFOR/Pfl) pathways. Therefore, this report provides direct genetic and physiological evidences of mixotrophic inorganic carbon-capture by C. beijerinckii. PMID- 28986543 TI - Organs on chip approach: a tool to evaluate cancer -immune cells interactions. AB - In this paper we discuss the applicability of numerical descriptors and statistical physics concepts to characterize complex biological systems observed at microscopic level through organ on chip approach. To this end, we employ data collected on a microfluidic platform in which leukocytes can move through suitably built channels toward their target. Leukocyte behavior is recorded by standard time lapse imaging. In particular, we analyze three groups of human peripheral blood mononuclear cells (PBMC): heterozygous mutants (in which only one copy of the FPR1 gene is normal), homozygous mutants (in which both alleles encoding FPR1 are loss-of-function variants) and cells from 'wild type' donors (with normal expression of FPR1). We characterize the migration of these cells providing a quantitative confirmation of the essential role of FPR1 in cancer chemotherapy response. Indeed wild type PBMC perform biased random walks toward chemotherapy-treated cancer cells establishing persistent interactions with them. Conversely, heterozygous mutants present a weaker bias in their motion and homozygous mutants perform rather uncorrelated random walks, both failing to engage with their targets. We next focus on wild type cells and study the interactions of leukocytes with cancerous cells developing a novel heuristic procedure, inspired by Lyapunov stability in dynamical systems. PMID- 28986544 TI - A Novel Mouse Model of iNKT Cell-deficiency Generated by CRISPR/Cas9 Reveals a Pathogenic Role of iNKT Cells in Metabolic Disease. AB - iNKT cells play important roles in immune regulation by bridging the innate and acquired immune systems. The functions of iNKT cells have been investigated in mice lacking the Traj18 gene segment that were generated by traditional embryonic stem cell technology, but these animals contain a biased T cell receptor (TCR) repertoire that might affect immune responses. To circumvent this confounding factor, we have generated a new strain of iNKT cell-deficient mice by deleting the Traj18 locus using CRISPR/Cas9 technology, and these animals contain an unbiased TCR repertoire. We employed these mice to investigate the contribution of iNKT cells to metabolic disease and found a pathogenic role of these cells in obesity-associated insulin-resistance. The new Traj18-deficient mouse strain will assist in studies of iNKT cell biology. PMID- 28986545 TI - Genetic variants affecting equivalent protein family positions reflect human diversity. AB - Members of diverse protein families often perform overlapping or redundant functions meaning that different variations within them could reflect differences between individual organisms. We investigated likely functional positions within aligned protein families that contained a significant enrichment of nonsynonymous variants in genomes of healthy individuals. We identified more than a thousand enriched positions across hundreds of family alignments with roles indicative of mammalian individuality, including sensory perception and the immune system. The most significant position is the Arginine from the Olfactory receptor "DRY" motif, which has more variants in healthy individuals than all other positions in the proteome. Odorant binding data suggests that these variants lead to receptor inactivity, and they are mostly mutually exclusive with other loss-of-function (stop/frameshift) variants. Some DRY Arginine variants correlate with smell preferences in sub-populations and all 2,504 humans studied contain a unique spectrum of active and inactive receptors. The many other variant enriched positions, across hundreds of other families might also provide insights into individual differences. PMID- 28986546 TI - Imaging Atomic Scale Dynamics on III-V Nanowire Surfaces During Electrical Operation. AB - As semiconductor electronics keep shrinking, functionality depends on individual atomic scale surface and interface features that may change as voltages are applied. In this work we demonstrate a novel device platform that allows scanning tunneling microscopy (STM) imaging with atomic scale resolution across a device simultaneously with full electrical operation. The platform presents a significant step forward as it allows STM to be performed everywhere on the device surface and high temperature processing in reactive gases of the complete device. We demonstrate the new method through proof of principle measurements on both InAs and GaAs nanowire devices with variable biases up to 4 V. On InAs nanowires we observe a surprising removal of atomic defects and smoothing of the surface morphology under applied bias, in contrast to the expected increase in defects and electromigration-related failure. As we use only standard fabrication and scanning instrumentation our concept is widely applicable and opens up the possibility of fundamental investigations of device surface reliability as well as new electronic functionality based on restructuring during operation. PMID- 28986547 TI - Association of Plasma Magnesium with Prediabetes and Type 2 Diabetes Mellitus in Adults. AB - Our study aimed to assess the associations of plasma magnesium with prediabetes and type 2 diabetes (T2D) among Chinese adults. We conducted a case-control analysis of 4447 participants: 867 newly diagnosed prediabetes patients, 1475 newly diagnosed T2D patients and 2105 normal glucose tolerance (NGT) individuals. In a subsample of 599 apparently healthy individuals, we measured plasma hs-CRP levels to examine their relation to plasma magnesium. Plasma magnesium and hs-CRP were measured by inductively coupled plasma mass spectrometry and an enzyme linked immunosorbent assay, respectively. Plasma magnesium decreased from NGT to prediabetes to T2D, and was inversely associated with prediabetes and T2D. After adjustment for potential confounding factors, the ORs from the lowest to highest quartiles of plasma magnesium were 1, 0.57 (95%CI, 0.44-0.74), 0.49 (0.37-0.65) and 0.51 (0.37-0.70) for prediabetes, and 1, 0.26 (0.20-0.33), 0.15 (0.12-0.20) and 0.15 (0.11-0.20) for T2D. Consistently, plasma magnesium was inversely correlated with plasma hs-CRP in our subsample analysis; the geometric mean hs CRP concentration for ascending quartiles of plasma magnesium were 1.29 (1.06 1.57), 1.16 (0.95-1.41), 1.00 (0.81-1.22), and 0.71 (0.58-0.88) mg/l. Plasma magnesium was independently and inversely associated with prediabetes and T2D in Chinese adults. PMID- 28986548 TI - Structure-Activity Relationship Studies of beta-Lactam-azide Analogues as Orally Active Antitumor Agents Targeting the Tubulin Colchicine Site. AB - We have synthesized a series of new beta-lactam-azide derivatives as orally active anti-tumor agents by targeting tubulin colchicine binding site and examined their structure activity relationship (SAR). Among them, compound 28 exhibited the most potent antiproliferative activity against MGC-803 cells with an IC50 value of 0.106 MUM by induction of G2/M arrest and apoptosis and inhibition of the epithelial to mesenchymal transition. 28 acted as a novel inhibitor of tubulin polymerization by its binding to the colchicine site. SAR analysis revealed that a hydrogen atom at the C-3 position of the beta-lactam was required for the potent antiproliferative activity of beta-lactam-azide derivatives. Oral administration of compound 28 also effectively inhibited MGC 803 xenograft tumor growth in vivo in nude mice without causing significant loss of body weight. These results suggested that compound 28 is a promising orally active anticancer agent with potential for development of further clinical applications. PMID- 28986549 TI - Is Long-term Exposure to Air Pollution Associated with Episodic Memory? A Longitudinal Study from Northern Sweden. AB - Associations between long-term exposure to ambient air pollution and cognitive function have been observed in a few longitudinal studies. Our aim was to investigate the association between long-term exposure to air pollution and episodic memory, a marker of early cognitive decline. We used data from the Betula study in Northern Sweden, and included participants 60 to 85 of age at inclusion, 1,469 persons in total. The participants were followed for up to 22 years, five years apart between 1988 and 2010. A composite of five tasks was used as a measure of episodic memory measure (EMM), and the five-year change in EMM score (DeltaEMM) was calculated such that a participant could contribute with up to four measurement pairs. A Land Use Regression Model was used to estimate cumulative annual mean of NOx at the residential address of the participants (a marker for long-term exposure to traffic-related air pollution). There did not seem to be any association between exposure to traffic air pollution and episodic memory change, with a DeltaEMM estimate of per 1 ug/m3 increase in NOx of 0.01 (95% Confidence Interval: -0.02,0.03). This is in contrast to a growing body of evidence suggesting associations between air pollution and cognitive function. PMID- 28986550 TI - Pterostilbene, a natural phenolic compound, synergizes the antineoplastic effects of megestrol acetate in endometrial cancer. AB - Endometrial cancer is the most common gynecologic cancer in the United States and its incidence and mortality has been rising over the past decade. Few treatment options are available for patients with advanced and recurring endometrial cancers. Novel therapies, which are frequently toxic, are difficult to establish in this patient population which tends to be older and plagued by comorbidities such as diabetes mellitus and hypertension. Therefore, novel, non-toxic therapies are urgently needed. Megestrol acetate is a frequently used drug in endometrial cancer patients. However, its response rate is only 20-30%. To enhance the activity of megestrol acetate in endometrial cancer patients, we explored the potential of combining natural supplements with megestrol acetate and found that the addition of the natural phenolic compound, pterostilbene, to megestrol acetate resulted in a synergistic inhibition of cancer cell growth in vitro and an enhanced reduction of tumor growth in a xenograft mouse model. In addition, dual treatment led to attenuation of signaling pathways, as well as cell cycle and survival pathways. Our results demonstrated for the first time that the anti tumor activity of megestrol acetate can be enhanced by combining with pterostilbene, providing an insight into the potential application of pterostilbene and megestrol acetate combination for the treatment of endometrial cancer. PMID- 28986551 TI - Towards remote assessment and screening of acute abdominal pain using only a smartphone with native accelerometers. AB - Smartphone-based telehealth holds the promise of shifting healthcare from the clinic to the home, but the inability for clinicians to conduct remote palpation, or touching, a key component of the physical exam, remains a major limitation. This is exemplified in the assessment of acute abdominal pain, in which a physician's palpation determines if a patient's pain is life-threatening requiring emergency intervention/surgery or due to some less-urgent cause. In a step towards virtual physical examinations, we developed and report for the first time a "touch-capable" mHealth technology that enables a patient's own hands to serve as remote surrogates for the physician's in the screening of acute abdominal pain. Leveraging only a smartphone with its native accelerometers, our system guides a patient through an exact probing motion that precisely matches the palpation motion set by the physician. An integrated feedback algorithm, with 95% sensitivity and specificity, enabled 81% of tested patients to match a physician abdominal palpation curve with <20% error after 6 attempts. Overall, this work addresses a key issue in telehealth that will vastly improve its capabilities and adoption worldwide. PMID- 28986552 TI - Phylogeny, historical biogeography and characters evolution of the drought resistant fern Pyrrosia Mirbel (Polypodiaceae) inferred from plastid and nuclear markers. AB - Pyrrosia s.l. comprises ca. 60 species with a disjunct Africa/Asia and Australia distribution. The infrageneric classification of Pyrrosia s.l. is controversial based on the phylogenetic analyses of chloroplast markers and morphology. Based on the expanded taxon sampling of Pyrrosia s.l. (51 species), we investigated its phylogeny, biogeography, character evolution and environmental adaptation by employing five chloroplastid markers (rbcL, matK, psbA-trnH, and rps4 + rps4 trnS) and one single (low)-copy nuclear gene, LEAFY. Pyrrosia s.l. was divided into six major clades and eight subclades. Reticulate evolution was revealed both among clades and among species in Pyrrosia s.l. Ancestral character state optimization revealed high levels of homoplastic evolution of the diagnostic characters in Pyrrosia s.l., while the crassulacean acid metabolism pathway seems to have an independent origin. Molecular dating and biogeographic diversification analyses suggested that Pyrrosia s.l. originated no later than the Oligocene and the main clades diversified during the Oligocene and Miocene, with southern Asia, the Indo-China Peninsula and southwestern and southern China as the most likely ancestral areas. Transoceanic long-distance dispersal, rather than vicariance, contributed to the intercontinental disjunction. Diversification scenarios of Pyrrosia s.l. under geological movements and climate fluctuation are also discussed. PMID- 28986553 TI - Brain atrophy in the visual cortex and thalamus induced by severe stress in animal model. AB - Psychological stress induces many diseases including post-traumatic stress disorder (PTSD); however, the causal relationship between stress and brain atrophy has not been clarified. Applying single-prolonged stress (SPS) to explore the global effect of severe stress, we performed brain magnetic resonance imaging (MRI) acquisition and Voxel-based morphometry (VBM). Significant atrophy was detected in the bilateral thalamus and right visual cortex. Fluorescent immunohistochemistry for Iba-1 as the marker of activated microglia indicates regional microglial activation as stress-reaction in these atrophic areas. These data certify the impact of severe psychological stress on the atrophy of the visual cortex and the thalamus. Unexpectedly, these results are similar to chronic neuropathic pain rather than PTSD clinical research. We believe that some sensitisation mechanism from severe stress-induced atrophy in the visual cortex and thalamus, and the functional defect of the visual system may be a potential therapeutic target for stress-related diseases. PMID- 28986554 TI - Transition of Femtosecond-Filament-Solid Interactions from Single to Multiple Filament Regime. AB - High-peak-power fs-laser filaments offer unique characteristics attractive to remote sensing via techniques such as remote laser-induced breakdown spectroscopy (R-LIBS). The dynamics of several ablation mechanisms following the interaction between a filament and a solid determines the emission strength and reproducibility of target plasma, which is of relevance for R-LIBS applications. We investigate the space- and time-resolved dynamics of ionic and atomic emission from copper as well as the surrounding atmosphere in order to understand limitations of fs-filament-ablation for standoff energy delivery. Furthermore, we probe the shock front produced from filament-target interaction using time resolved shadowgraphy and infer laser-material coupling efficiencies for both single and multiple filament regimes through analysis of shock expansion with the Sedov model for point detonation. The results provide insight into plasma structure for the range of peak powers up to 30 times the critical power for filamentation P cr . Despite the stochastic nucleation of multiple filaments at peak-powers greater than 16 P cr , emission of ionic and neutral species increases with pump beam intensity, and short-lived nitrogen emission originating from the ambient is consistently observed. Ultimately, results suggest favorable scaling of emission intensity from target species on the laser pump energy, furthering the prospects for use of filament-solid interactions for remote sensing. PMID- 28986555 TI - Multilayer pixel super-resolution lensless in-line holographic microscope with random sample movement. AB - We report a multilayer lensless in-line holographic microscope (LIHM) with improved imaging resolution by using the pixel super-resolution technique and random sample movement. In our imaging system, a laser beam illuminated the sample and a CMOS imaging sensor located behind the sample recorded the in-line hologram for image reconstruction. During the imaging process, the sample was moved by hand randomly and the in-line holograms were acquired sequentially. Then the sample image was reconstructed from an enhanced-resolution hologram obtained from multiple low-resolution in-line holograms by applying the pixel super resolution (PSR) technique. We studied the resolution enhancement effects by using the U.S. Air Force (USAF) target as the sample in numerical simulation and experiment. We also showed that multilayer pixel super-resolution images can be obtained by imaging a triple-layer sample made with the filamentous algae on the middle layer and microspheres with diameter of 2 MUm on the top and bottom layers. Our pixel super-resolution LIHM provides a compact and low-cost solution for microscopic imaging and is promising for many biomedical applications. PMID- 28986556 TI - Clinical implication of ectopic liver lipid accumulation in renal cell carcinoma patients without visceral obesity. AB - Fatty liver has emerged as a prognostic marker of cancer, so we investigated the impact of ectopic lipid accumulation in liver on the clinical outcome for patients with renal cell carcinoma (RCC). The records of 230 consecutive patients who had undergone surgery for RCC were reviewed, and liver lipid accumulation was estimated from the attenuation in unenhanced preoperative CT images. The median liver CT values of patients with G3 tumors was lower than that of patients with G1-2 tumors (P = 0.0116), that of patients with pT3-4 tumors was lower than that of patients with pT1-2 tumors (P = 0.0336), and that of patients with visceral obesity defined as a visceral fat area >= 100 cm2 was lower than that of patients without visceral obesity (P < 0.0001). In patients without visceral obesity the median liver CT values of patients with pT3-4 tumors was lower than that of patients with pT1-2 tumors (P = 0.0401), that of patients with metastasis was lower than that of patients without metastasis (P = 0.026), and fatty liver was associated with shorter overall survival (P = 0.0009). Ectopic lipid accumulation in liver thus seems to be a predictor of aggressive forms of RCC. PMID- 28986557 TI - Antireflection coating of barriers to enhance electron tunnelling: exploring the matter wave analogy of superluminal optical phase velocity. AB - The tunnelling of electrons through barriers is important in field emission sources and in interconnects within electronic devices. Here we use the analogy between the electromagnetic wave equation and the Schrodinger equation to find potential barriers that, when added before an existing barrier, increase the transmission probability. A single pre-barrier of negative potential behaves as a dielectric "antireflection coating", as previously reported. However, we obtain an unexpected and much greater enhancement of transmission when the pre-barrier has a positive potential of height smaller than the energy of the incident electron, an unfamiliar optical case, corresponding to media with superluminal phase velocities as in dilute free electron media and anomalous dispersion at X ray frequencies. We use a finite difference time domain algorithm to evaluate the transmission through a triangular field emission barrier with a pre-barrier that meets the new condition. We show that the transmission is enhanced for an incident wavepacket, producing a larger field emission current than for an uncoated barrier. Examples are given of available materials to enhance transmission in practical applications. The results are significant for showing how to increase electron transmission in field emission and at interconnects between dissimilar materials in all types of electronic devices. PMID- 28986558 TI - Determination of a potential quantitative measure of the state of the lung using lung ultrasound spectroscopy. AB - B-lines are ultrasound-imaging artifacts, which correlate with several lung pathologies. However, their understanding and characterization is still largely incomplete. To further study B-lines, lung-phantoms were developed by trapping a layer of microbubbles in tissue-mimicking gel. To simulate the alveolar size reduction typical of various pathologies, 170 and 80 um bubbles were used for phantom-type 1 and 2, respectively. A normal alveolar diameter is approximately 280 um. A LA332 linear-array connected to the ULA-OP platform was used for imaging. Standard ultrasound (US) imaging at 4.5 MHz was performed. Subsequently, a multi-frequency approach was used where images were sequentially generated using orthogonal sub-bands centered at different frequencies (3, 4, 5, and 6 MHz). Results show that B-lines appear predominantly with phantom-type 2. Moreover, the multi-frequency approach revealed that the B-lines originate from a specific portion of the US spectrum. These results can give rise to significant clinical applications since, if further confirmed by extensive in-vivo studies, the native frequency of B-lines could provide a quantitative-measure of the state of the lung. PMID- 28986559 TI - Zeeman splitting via spin-valley-layer coupling in bilayer MoTe2. AB - Atomically thin monolayer transition metal dichalcogenides possess coupling of spin and valley degrees of freedom. The chirality is locked to identical valleys as a consequence of spin-orbit coupling and inversion symmetry breaking, leading to a valley analog of the Zeeman effect in presence of an out-of-plane magnetic field. Owing to the inversion symmetry in bilayers, the photoluminescence helicity should no longer be locked to the valleys. Here we show that the Zeeman splitting, however, persists in 2H-MoTe2 bilayers, as a result of an additional degree of freedom, namely the layer pseudospin, and spin-valley-layer locking. Unlike monolayers, the Zeeman splitting in bilayers occurs without lifting valley degeneracy. The degree of circularly polarized photoluminescence is tuned with magnetic field from -37% to 37%. Our results demonstrate the control of degree of freedom in bilayer with magnetic field, which makes bilayer a promising platform for spin-valley quantum gates based on magnetoelectric effects.Monolayer transition metal dichalcogenides host a valley splitting in magnetic field analogous to the Zeeman effect. Here, the authors report that the Zeeman splitting still persists in bilayers of MoTe2 without lifting the valley degeneracy, due to spin-valley-layer coupling. PMID- 28986560 TI - The telomere binding protein Pot1 maintains haematopoietic stem cell activity with age. AB - Repeated cell divisions and aging impair stem cell function. However, the mechanisms by which this occurs are not fully understood. Here we show that protection of telomeres 1A (Pot1a), a component of the Shelterin complex that protects telomeres, improves haematopoietic stem cell (HSC) activity during aging. Pot1a is highly expressed in young HSCs, but declines with age. In mouse HSCs, Pot1a knockdown increases DNA damage response (DDR) and inhibits self renewal. Conversely, Pot1a overexpression or treatment with POT1a protein prevents DDR, maintained self-renewal activity and rejuvenated aged HSCs upon ex vivo culture. Moreover, treatment of HSCs with exogenous Pot1a inhibits the production of reactive oxygen species, suggesting a non-telomeric role for Pot1a in HSC maintenance. Consistent with these results, treatment with exogenous human POT1 protein maintains human HSC activity in culture. Collectively, these results show that Pot1a/POT1 sustains HSC activity and can be used to expand HSC numbers ex vivo.Repeated cell divisions induce DNA damage in haematopoietic stem cells (HSC) and telomeres are sensitive to this damage. Here, the authors show in murine HSCs that the telomere binding protein POT1a inhibited the production of reactive oxygen species, and rejuvenated aged HSCs. PMID- 28986562 TI - Ultrafast giant magnetic cooling effect in ferromagnetic Co/Pt multilayers. AB - The magnetic cooling effect originates from a large change in entropy by the forced magnetization alignment, which has long been considered to be utilized as an alternative environment-friendly cooling technology compared to conventional refrigeration. However, an ultimate timescale of the magnetic cooling effect has never been studied yet. Here, we report that a giant magnetic cooling (up to 200 K) phenomenon exists in the Co/Pt nano-multilayers on a femtosecond timescale during the photoinduced demagnetization and remagnetization, where the disordered spins are more rapidly aligned, and thus magnetically cooled, by the external magnetic field via the lattice-spin interaction in the multilayer system. These findings were obtained by the extensive analysis of time-resolved magneto-optical responses with systematic variation of laser fluence as well as external field strength and direction. Ultrafast giant magnetic cooling observed in the present study can enable a new avenue to the realization of ultrafast magnetic devices.The forced alignment of magnetic moments leads to a large change in entropy, which can be used to reduce the temperature of a material. Here, the authors show that this magnetic cooling effect occurs on a femtosecond time scale in cobalt-platinum nano-multilayers. PMID- 28986561 TI - Galectin-3 captures interferon-gamma in the tumor matrix reducing chemokine gradient production and T-cell tumor infiltration. AB - The presence of T cells in tumors predicts overall survival for cancer patients. However, why most tumors are poorly infiltrated by T cells is barely understood. T-cell recruitment towards the tumor requires a chemokine gradient of the critical IFNgamma-induced chemokines CXCL9/10/11. Here, we describe how tumors can abolish IFNgamma-induced chemokines, thereby reducing T-cell attraction. This mechanism requires extracellular galectin-3, a lectin secreted by tumors. Galectins bind the glycans of glycoproteins and form lattices by oligomerization. We demonstrate that galectin-3 binds the glycans of the extracellular matrix and those decorating IFNgamma. In mice bearing human tumors, galectin-3 reduces IFNgamma diffusion through the tumor matrix. Galectin antagonists increase intratumoral IFNgamma diffusion, CXCL9 gradient and tumor recruitment of adoptively transferred human CD8+ T cells specific for a tumor antigen. Transfer of T cells reduces tumor growth only if galectin antagonists are injected. Considering that most human cytokines are glycosylated, galectin secretion could be a general strategy for tumor immune evasion.Most tumours are poorly infiltrated by T cells. Here the authors show that galectin-3 secreted by tumours binds both glycosylated IFNgamma and glycoproteins of the tumour extracellular matrix, thus avoiding IFNgamma diffusion and the formation of an IFNgamma-induced chemokine gradient required for T cell infiltration. PMID- 28986563 TI - Impact of sequencing depth and read length on single cell RNA sequencing data of T cells. AB - Single cell RNA sequencing (scRNA-seq) provides great potential in measuring the gene expression profiles of heterogeneous cell populations. In immunology, scRNA seq allowed the characterisation of transcript sequence diversity of functionally relevant T cell subsets, and the identification of the full length T cell receptor (TCRalphabeta), which defines the specificity against cognate antigens. Several factors, e.g. RNA library capture, cell quality, and sequencing output affect the quality of scRNA-seq data. We studied the effects of read length and sequencing depth on the quality of gene expression profiles, cell type identification, and TCRalphabeta reconstruction, utilising 1,305 single cells from 8 publically available scRNA-seq datasets, and simulation-based analyses. Gene expression was characterised by an increased number of unique genes identified with short read lengths (<50 bp), but these featured higher technical variability compared to profiles from longer reads. Successful TCRalphabeta reconstruction was achieved for 6 datasets (81% - 100%) with at least 0.25 millions (PE) reads of length >50 bp, while it failed for datasets with <30 bp reads. Sufficient read length and sequencing depth can control technical noise to enable accurate identification of TCRalphabeta and gene expression profiles from scRNA-seq data of T cells. PMID- 28986564 TI - Dynamics of functional connectivity at high spatial resolution reveal long-range interactions and fine-scale organization. AB - Dynamic functional connectivity (dFC) derived from resting-state functional magnetic resonance imaging sheds light onto moment-to-moment reconfigurations of large-scale functional brain networks. Due to computational limits, connectivity is typically computed using pre-defined atlases, a non-trivial choice that might influence results. Here, we leverage new computational methods to retrieve dFC at the voxel level in terms of dominant patterns of fluctuations, and demonstrate that this new representation is informative to derive meaningful brain parcellations, capturing both long-range interactions and fine-scale local organization. Specifically, voxelwise dFC dominant patterns were captured through eigenvector centrality followed by clustering across time/subjects to yield most representative dominant patterns (RDPs). Voxel-wise labeling according to positive/negative contributions to RDPs, led to 37 unique labels identifying strikingly symmetric dFC long-range patterns. These included 449 contiguous regions, defining a fine-scale parcellation consistent with known cortical/subcortical subdivisions. Our contribution provides an alternative to obtain a whole-brain parcellation that is for the first time driven by voxel level dFC and bridges the gap between voxel-based approaches and graph theoretical analysis. PMID- 28986565 TI - Activation-Induced Conformational Changes of Dopamine D3 Receptor Promote the Formation of the Internal Water Channel. AB - The atomic-level dopamine activation mechanism for transmitting extracellular ligand binding events through transmembrane helices to the cytoplasmic G protein remains unclear. In the present study, the complete dopamine D3 receptor (D3R), with a homology-modeled N-terminus, was constructed to dock different ligands to simulate conformational alterations in the receptor's active and inactive forms during microsecond-timescale molecular dynamic simulations. In agonist-bound systems, the D3R N-terminus formed a "lid-like" structure and lay flat on the binding site opening, whereas in antagonist and inverse agonist-bound systems, the N-terminus exposed the binding cavity. Receptor activation was characterized using the different molecular switch residue distances, and G protein-binding site volumes. A continuous water pathway was observed only in the dopamine Galphai-bound system. In the inactive D3Rs, water entry was hindered by the hydrophobic layers. Finally, a complete activation mechanism of D3R was proposed. Upon agonist binding, the "lid-like" conformation of the N-terminus induces a series of molecular switches to increase the volume of the D3R cytoplasmic binding part for G protein association. Meanwhile, water enters the transmembrane region inducing molecular switches to assist in opening the hydrophobic layers to form a continuous water channel, which is crucial for maintaining a fully active conformation for signal transduction. PMID- 28986566 TI - Association between MGMT Promoter Methylation and Risk of Breast and Gynecologic Cancers: A Systematic Review and Meta-Analysis. AB - The role of the promoter methylation of O 6-methylguanine-DNA methyltransferase (MGMT) remains controversial for breast and gynecologic cancers. We conducted a meta-analysis to assess the association between hypermethylation of MGMT promoter and the risk of breast and gynecologic cancers. A comprehensive search was conducted in PubMed and Embase electronic databases up to 19th August 2017 for studies about the association between MGMT promoter hypermethylation and breast and gynecologic cancers. A total of 28 articles including 2,171 tumor tissues and 1,191 controls were involved in the meta-analysis. The pooled results showed that MGMT promoter methylation status was significantly associated with an increased risk of breast and gynecologic cancers (OR = 4.37, 95% CI: 2.68-7.13, P < 0.05). The associations were robust in subgroup analysis based on ethnicity, cancer type, methylation detection method, and control source. This meta-analysis indicated that MGMT hypermethylation was significantly associated with the risk of breast and gynecological cancers, and it may be utilized as a valuable biomarker in early diagnostics and prognostication of these cancers. Further efforts are needed to identify and validate this finding in prospective studies, especially in situation with new methylation testing methods and samples from plasma circulating DNA. PMID- 28986567 TI - Enhancing excitatory activity of somatosensory cortex alleviates neuropathic pain through regulating homeostatic plasticity. AB - Central sensitization and network hyperexcitability of the nociceptive system is a basic mechanism of neuropathic pain. We hypothesize that development of cortical hyperexcitability underlying neuropathic pain may involve homeostatic plasticity in response to lesion-induced somatosensory deprivation and activity loss, and can be controlled by enhancing cortical activity. In a mouse model of neuropathic pain, in vivo two-photon imaging and patch clamp recording showed initial loss and subsequent recovery and enhancement of spontaneous firings of somatosensory cortical pyramidal neurons. Unilateral optogenetic stimulation of cortical pyramidal neurons both prevented and reduced pain-like behavior as detected by bilateral mechanical hypersensitivity of hindlimbs, but corpus callosotomy eliminated the analgesic effect that was ipsilateral, but not contralateral, to optogenetic stimulation, suggesting involvement of inter hemispheric excitatory drive in this effect. Enhancing activity by focally blocking cortical GABAergic inhibition had a similar relieving effect on the pain like behavior. Patch clamp recordings from layer V pyramidal neurons showed that optogenetic stimulation normalized cortical hyperexcitability through changing neuronal membrane properties and reducing frequency of excitatory postsynaptic events. We conclude that development of neuropathic pain involves abnormal homeostatic activity regulation of somatosensory cortex, and that enhancing cortical excitatory activity may be a novel strategy for preventing and controlling neuropathic pain. PMID- 28986569 TI - Algorithm guided outlining of 105 pancreatic cancer liver metastases in Ultrasound. AB - Manual segmentation of hepatic metastases in ultrasound images acquired from patients suffering from pancreatic cancer is common practice. Semiautomatic measurements promising assistance in this process are often assessed using a small number of lesions performed by examiners who already know the algorithm. In this work, we present the application of an algorithm for the segmentation of liver metastases due to pancreatic cancer using a set of 105 different images of metastases. The algorithm and the two examiners had never assessed the images before. The examiners first performed a manual segmentation and, after five weeks, a semiautomatic segmentation using the algorithm. They were satisfied in up to 90% of the cases with the semiautomatic segmentation results. Using the algorithm was significantly faster and resulted in a median Dice similarity score of over 80%. Estimation of the inter-operator variability by using the intra class correlation coefficient was good with 0.8. In conclusion, the algorithm facilitates fast and accurate segmentation of liver metastases, comparable to the current gold standard of manual segmentation. PMID- 28986568 TI - Bik reduces hyperplastic cells by increasing Bak and activating DAPk1 to juxtapose ER and mitochondria. AB - Bik reduces hyperplastic epithelial cells by releasing calcium from endoplasmic reticulum stores and causing apoptosis, but the detailed mechanisms are not known. Here we report that Bik dissociates the Bak/Bcl-2 complex to enrich for ER associated Bak and interacts with the kinase domain of DAPk1 to form Bik-DAPk1 ERK1/2-Bak complex. Bik also disrupts the Bcl2-IP3R interaction to cause ER Ca2+ release. The ER-associated Bak interacts with the kinase and calmodulin domains of DAPk1 to increase the contact sites of ER and mitochondria, and facilitate ER Ca2+ uptake by mitochondria. Although the Bik BH3 helix was sufficient to enrich for ER-Bak and elicit ER Ca2+ release, Bik-induced mitochondrial Ca2+ uptake is blocked with reduced Bak levels. Further, the Bik-derived peptide reduces allergen- and cigarette smoke-induced mucous cell hyperplasia in mice and in differentiated primary human airway epithelial cultures. Therefore, Bik peptides may have therapeutic potential in airway diseases associated with chronic mucous hypersecretion.Bcl-2 interacting killer (Bik) decreases airway epithelial hyperplasia via apoptosis mediated by calcium release from the endoplasmic reticulum (ER), but the mechanism is unclear. Here the authors show that Bik promotes Bak enrichment at the ER to tether mitochondria for efficient calcium transfer. PMID- 28986570 TI - Conformations and molecular interactions of poly-gamma-glutamic acid as a soluble microbial product in aqueous solutions. AB - Soluble microbial products (SMPs) are of significant concern in the natural environment and in engineered systems. In this work, poly-gamma-glutamic acid (gamma-PGA), which is predominantly produced by Bacillus sp., was investigated in terms of pH-induced conformational changes and molecular interactions in aqueous solutions; accordingly, its sedimentation coefficient distribution and viscosity were also elucidated. Experimental results indicate that pH has a significant impact on the structure and molecular interactions of gamma-PGA. The conformation of the gamma-PGA acid form (gamma-PGA-H) is rod-like while that of the gamma-PGA sodium form (gamma-PGA-Na) is sphere-like. The transformation from alpha-helix to random coil in the gamma-PGA secondary structure is primarily responsible for this shape variation. The intramolecular hydrogen bonds in the gamma-PGA-H structure decrease and intramolecular electrostatic repulsion increases as pH increases; however, the sedimentation coefficient distributions of gamma-PGA are dependent on intermolecular interactions rather than intramolecular interactions. Concentration has a more substantial effect on intermolecular electrostatic repulsion and chain entanglement at higher pH values. Consequently, the sedimentation coefficient distributions of gamma-PGA shift significantly at pH 8.9 from 0.1 to 1.0 g/L, and the viscosity of gamma-PGA (5% w/v) significantly increases as pH increases from 2.3 to 6.0. PMID- 28986571 TI - A high-density linkage map and QTL mapping of fruit-related traits in pumpkin (Cucurbita moschata Duch.). AB - Pumpkin (Cucurbita moschata) is an economically worldwide crop. Few quantitative trait loci (QTLs) were reported previously due to the lack of genomic and genetic resources. In this study, a high-density linkage map of C. moschata was structured by double-digest restriction site-associated DNA sequencing, using 200 F2 individuals of CMO-1 * CMO-97. By filtering 74,899 SNPs, a total of 3,470 high quality SNP markers were assigned to the map spanning a total genetic distance of 3087.03 cM on 20 linkage groups (LGs) with an average genetic distance of 0.89 cM. Based on this map, both pericarp color and strip were fined mapped to a novel single locus on LG8 in the same region of 0.31 cM with phenotypic variance explained (PVE) of 93.6% and 90.2%, respectively. QTL analysis was also performed on carotenoids, sugars, tuberculate fruit, fruit diameter, thickness and chamber width with a total of 12 traits. 29 QTLs distributed in 9 LGs were detected with PVE from 9.6% to 28.6%. It was the first high-density linkage SNP map for C. moschata which was proved to be a valuable tool for gene or QTL mapping. This information will serve as significant basis for map-based gene cloning, draft genome assembling and molecular breeding. PMID- 28986572 TI - Moire Superstructure and Dimensional Crossover of 2D Electronic States on Nanoscale Lead Quantum Films. AB - We investigate using scanning tunneling microscopy and spectroscopy electronic aspects of Moire superstructures in nanoscale Pb quantum films grown on IrTe2, which is a unique layered material with charge-order transitions into stripe phases. Pb ultrathin films exhibit a Moire superstructure due to the lattice mismatch of Pb and IrTe2, which produces strong lateral electronic modulation of hexagonal symmetry and discreet subbands. Moreover, strongly anisotropic or 1D electronic states are formed in Pb films as modulated by the stripe charge order. Present results indicate the controllability of lateral electronic structures of various ultrathin films by extra interfacial potentials due not only to Moire superstructures but also to novel electronic orderings of substrates. PMID- 28986574 TI - All-optical control on a graphene-on-silicon waveguide modulator. AB - The hallmark of silicon photonics is in its low loss at the telecommunications wavelength, economic advantages and compatibility with CMOS design and fabrication processes. These advantages are however impeded by its relatively low Kerr coefficient that constrains the power and size scaling of nonlinear all optical silicon photonic devices. Graphene, with its unprecedented high Kerr coefficient and uniquely thin-film structure, makes a good nonlinear material to be easily integrated onto all-optical silicon photonic waveguide devices. We study the design of all-optical graphene-on-silicon (GOS) waveguide modulators, and find the optimized performance of MW cm-2 in optical pump intensities and sub mm device lengths. The improvements brought by the integration of graphene onto silicon photonic waveguides could bring us a step closer to realising compact all optical control on a single chip. PMID- 28986573 TI - Activin in acute pancreatitis: Potential risk-stratifying marker and novel therapeutic target. AB - Acute Pancreatitis is a substantial health care challenge with increasing incidence. Patients who develop severe disease have considerable mortality. Currently, no reliable predictive marker to identify patients at risk for severe disease exists. Treatment is limited to rehydration and supporting care suggesting an urgent need to develop novel approaches to improve standard care. Activin is a critical modulator of inflammatory responses, but has not been assessed in pancreatitis. Here, we demonstrate that serum activin is elevated and strongly correlates with disease severity in two established murine models of acute pancreatitis induced by either cerulein or IL-12 + IL-18. Furthermore, in mice, inhibition of activin conveys survival benefits in pancreatitis. In addition, serum activin levels were measured from a retrospective clinical cohort of pancreatitis patients and high activin levels in patients at admission are predictive of worse outcomes, indicated by longer overall hospital and intensive care unit stays. Taken together, activin is a novel candidate as a clinical marker to identify those acute pancreatitis patients with severe disease who would benefit from aggressive treatment and activin may be a therapeutic target in severe acute pancreatitis. PMID- 28986575 TI - DNA metabarcoding and morphological macroinvertebrate metrics reveal the same changes in boreal watersheds across an environmental gradient. AB - Cost-effective, ecologically relevant, sensitive, and standardized indicators are requisites of biomonitoring. DNA metabarcoding of macroinvertebrate communities is a potentially transformative biomonitoring technique that can reduce cost and time constraints while providing information-rich, high resolution taxonomic data for the assessment of watershed condition. Here, we assess the utility of DNA metabarcoding to provide aquatic indicator data for evaluation of forested watershed condition across Canadian eastern boreal watersheds, subject to natural variation and low-intensity harvest management. We do this by comparing the similarity of DNA metabarcoding and morphologically derived macroinvertebrate metrics (i.e. richness, % Ephemeroptera, Plecoptera and Trichoptera, % chironomid), and the ability of DNA metabarcoding and morphological metrics to detect key gradients in stream condition linked to forested watershed features. Our results show consistency between methods, where common DNA metabarcoding and morphological macroinvertebrate metrics are positively correlated and indicate the same key gradients in stream condition (i.e. dissolved oxygen, and dissolved organic carbon, total nitrogen and conductivity) linked to watershed size and shifts in forest composition across watersheds. Our study demonstrates the potential usefulness of macroinvertebrate DNA metabarcoding to future application in broad-scale biomonitoring of watershed condition across environmental gradients. PMID- 28986576 TI - Fractional Laser Releases Tumor-Associated Antigens in Poorly Immunogenic Tumor and Induces Systemic Immunity. AB - Currently ablative fractional photothermolysis (aFP) with CO2 laser is used for a wide variety of dermatological indications. This study presents and discusses the utility of aFP for treating oncological indications. We used a fractional CO2 laser and anti-PD-1 inhibitor to treat a tumor established unilaterally by the CT26 wild type (CT26WT) colon carcinoma cell line. Inoculated tumors grew significantly slower in aFP-treated groups (aFP and aFP + anti-PD-1 groups) and complete remission was observed in the aFP-treated groups. Flow cytometric analysis showed aFP treatment elicited an increase of CD3+, CD4+, CD8+ vand epitope specific CD8+ T cells. Moreover, the ratio of CD8+ T cells to Treg increased in the aFP-treated groups. Additionally, we established a bilateral CT26WT-inoculated mouse model, treating tumors on one-side and observing both tumors. Interestingly, tumors grew significantly slower in the aFP + anti-PD-1 groups and complete remission was observed for tumors on both aFP-treated and untreated sides. This study has demonstrated a potential role of aFP treatments in oncology. PMID- 28986577 TI - Replication defective viral genomes exploit a cellular pro-survival mechanism to establish paramyxovirus persistence. AB - Replication defective viral genomes (DVGs) generated during virus replication are the primary triggers of antiviral immunity in many RNA virus infections. However, DVGs can also facilitate viral persistence. Why and how these two opposing functions of DVGs are achieved remain unknown. Here we report that during Sendai and respiratory syncytial virus infections DVGs selectively protect a subpopulation of cells from death, thereby promoting the establishment of persistent infections. We find that during Sendai virus infection this phenotype results from DVGs stimulating a mitochondrial antiviral-signaling (MAVS)-mediated TNF response that drives apoptosis of highly infected cells while extending the survival of cells enriched in DVGs. The pro-survival effect of TNF depends on the activity of the TNFR2/TRAF1 pathway that is regulated by MAVS signaling. These results identify TNF as a pivotal factor in determining cell fate during a viral infection and delineate a MAVS/TNFR2-mediated mechanism that drives the persistence of otherwise acute viruses.Replication defective viral genomes (DVGs) can facilitate persistence of paramyxoviruses, but the underlying mechanisms are unclear. Using FISH, Xu et al. here analyze the cellular response to DVGs on a single cell level and show that a MAVS-mediated TNF response specifically extends survival of cells enriched in DVGs. PMID- 28986579 TI - Outcomes of 23- and 24-weeks gestation infants in Wellington, New Zealand: A single centre experience. AB - Optimal perinatal care of infants born less than 24 weeks gestation remains contentious due to uncertainty about the long-term neurodevelopment of resuscitated infants. Our aim was to determine the short-term mortality and major morbidity outcomes from a cohort of inborn infants born at 23 and 24 weeks gestation and to assess if these parameters differed significantly between infants born at 23 vs. 24 weeks gestation. We report survival rates at 2-year follow-up of 22/38 (58%) at 23 weeks gestation and 36/60 (60%) at 24 weeks gestation. Neuroanatomical injury at the time of discharge (IVH >= Grade 3 and/or PVL) occurred in in 3/23 (13%) and 1/40 (3%) of surviving 23 and 24 weeks gestation infants respectively. Rates of disability at 2 years corrected postnatal age were not different between infants born at 23 and 24 weeks gestation. We show evidence that with maximal perinatal care in a tertiary setting it is possible to achieve comparable rates of survival free of significant neuroanatomical injury or severe disability at age 2 in infants born at 23-week and 24-weeks gestation. PMID- 28986578 TI - Parvalbumin-expressing interneurons can act solo while somatostatin-expressing interneurons act in chorus in most cases on cortical pyramidal cells. AB - Neural circuits in the cerebral cortex consist primarily of excitatory pyramidal (Pyr) cells and inhibitory interneurons. Interneurons are divided into several subtypes, in which the two major groups are those expressing parvalbumin (PV) or somatostatin (SOM). These subtypes of interneurons are reported to play distinct roles in tuning and/or gain of visual response of pyramidal cells in the visual cortex. It remains unclear whether there is any quantitative and functional difference between the PV -> Pyr and SOM -> Pyr connections. We compared unitary inhibitory postsynaptic currents (uIPSCs) evoked by electrophysiological activation of single presynaptic interneurons with population IPSCs evoked by photo-activation of a mass of interneurons in vivo and in vitro in transgenic mice in which PV or SOM neurons expressed channelrhodopsin-2, and found that at least about 14 PV neurons made strong connections with a postsynaptic Pyr cell while a much larger number of SOM neurons made weak connections. Activation or suppression of single PV neurons modified visual responses of postsynaptic Pyr cells in 6 of 7 pairs whereas that of single SOM neurons showed no significant modification in 8 of 11 pairs, suggesting that PV neurons can act solo whereas most of SOM neurons may act in chorus on Pyr cells. PMID- 28986580 TI - Fenugreek supplementation during high-fat feeding improves specific markers of metabolic health. AB - To assess the metabolically beneficial effects of fenugreek (Trigonella foenum graecum), C57BL/6J mice were fed a low- or high-fat diet for 16 weeks with or without 2% (w/w) fenugreek supplementation. Body weight, body composition, energy expenditure, food intake, and insulin/glucose tolerance were measured regularly, and tissues were collected for histological and biochemical analysis after 16 weeks of diet exposure. Fenugreek did not alter body weight, fat mass, or food intake in either group, but did transiently improve glucose tolerance in high fat fed mice. Fenugreek also significantly improved high-density lipoprotein to low density lipoprotein ratios in high fat-fed mice without affecting circulating total cholesterol, triglycerides, or glycerol levels. Fenugreek decreased hepatic expression of fatty acid-binding protein 4 and increased subcutaneous inguinal adipose tissue expression of adiponectin, but did not prevent hepatic steatosis. Notably, fenugreek was not as effective at improving glucose tolerance as was four days of voluntary wheel running. Overall, our results demonstrate that fenugreek promotes metabolic resiliency via significant and selected effects on glucose regulation, hyperlipidemia, and adipose pathology; but may not be as effective as behavioral modifications at preventing the adverse metabolic consequences of a high fat diet. PMID- 28986581 TI - Nucleosome stability measured in situ by automated quantitative imaging. AB - Current approaches have limitations in providing insight into the functional properties of particular nucleosomes in their native molecular environment. Here we describe a simple and powerful method involving elution of histones using intercalators or salt, to assess stability features dependent on DNA superhelicity and relying mainly on electrostatic interactions, respectively, and measurement of the fraction of histones remaining chromatin-bound in the individual nuclei using histone type- or posttranslational modification- (PTM-) specific antibodies and automated, quantitative imaging. The method has been validated in H3K4me3 ChIP-seq experiments, by the quantitative assessment of chromatin loop relaxation required for nucleosomal destabilization, and by comparative analyses of the intercalator and salt induced release from the nucleosomes of different histones. The accuracy of the assay allowed us to observe examples of strict association between nucleosome stability and PTMs across cell types, differentiation state and throughout the cell-cycle in close to native chromatin context, and resolve ambiguities regarding the destabilizing effect of H2A.X phosphorylation. The advantages of the in situ measuring scenario are demonstrated via the marked effect of DNA nicking on histone eviction that underscores the powerful potential of topological relaxation in the epigenetic regulation of DNA accessibility. PMID- 28986582 TI - Assessing inhibitors of mutant isocitrate dehydrogenase using a suite of pre clinical discovery assays. AB - Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) are key metabolic enzymes that are mutated in a variety of cancers to confer a gain-of-function activity resulting in the accumulation of an oncometabolite, D-2-hydroxyglutarate (2-HG). Accumulation of 2-HG can result in epigenetic dysregulation and a block in cellular differentiation, suggesting these mutations play a role in neoplasia. Based on its potential as a cancer target, a number of small molecule inhibitors have been developed to specifically inhibit mutant forms of IDH (mIDH1 and mIDH2). We present a comprehensive suite of in vitro preclinical drug development assays that can be used as a tool-box to identify lead compounds for mIDH drug discovery programs, as well as what we believe is the most comprehensive publically available dataset on the top mIDH inhibitors. This involved biochemical, cell-based, and tier-one ADME techniques. PMID- 28986584 TI - 1700 nm and 1800 nm band tunable thulium doped mode-locked fiber lasers. AB - This paper presents short wavelength operation of tunable thulium-doped mode locked lasers with sweep ranges of 1702 to 1764 nm and 1788 to 1831 nm. This operation is realized by a combination of the partial amplified spontaneous emission suppression method, the bidirectional pumping mechanism and the nonlinear polarization rotation (NPR) technique. Lasing at emission bands lower than the 1800 nm wavelength in thulium-doped fiber lasers is achieved using mode confinement loss in a specially designed photonic crystal fiber (PCF). The enlargement of the first outer ring air holes around the core region of the PCF attenuates emissions above the cut-off wavelength and dominates the active region. This amplified spontaneous emission (ASE) suppression using our presented PCF is applied to a mode-locked laser cavity and is demonstrated to be a simple and compact solution to widely tunable all-fiber lasers. PMID- 28986583 TI - Effects of alpha-conotoxin ImI on TNF-alpha, IL-8 and TGF-beta expression by human macrophage-like cells derived from THP-1 pre-monocytic leukemic cells. AB - alpha7 nicotinic acetylcholine receptors (nAChRs) are ubiquitous in the nervous system and ensure important neurophysiological functionality for many processes. However, they are also found in cells of the immune system, where their role has been less studied. Here we report the pro-inflammatory effect of ImI, a well characterized conotoxin that inhibits alpha7 nAChRs, on differentiated THP-1 pre monocyte macrophages (MDM) obtained by phorbol 12-myristate 13 acetate (PMA) treatment. Enzyme-linked immunosorbent assay (ELISA) performed on supernatant fluids of LPS challenged MDM showed ImI-mediated upregulation of pro-inflammatory cytokine TNF-alpha in an ImI concentration-dependent manner from 0.5 to 5.0 umol/L and for IL-8 up to 1.0 umol/L. Levels of anti-inflammatory cytokine TGF beta remained practically unaffected in ImI treated MDMs. Nicotine at 10 umol/L significantly downregulated the release of TNF-alpha, but showed a lesser effect on IL-8 secretion and no effect on TGF-beta. Fluorescent competitive assays involving ImI, alpha-bungarotoxin and nicotine using MDM and the murine macrophage RAW 264.7 suggest a common binding site in the alpha7 receptor. This work extends the application of conotoxins as molecular probes to non-excitatory cells, such as macrophages and supports the involvement of the alpha7 nAChR in regulating the inflammatory response via the cholinergic anti-inflammatory pathway (CAP). PMID- 28986585 TI - Quantitation of putative colorectal cancer biomarker candidates in serum extracellular vesicles by targeted proteomics. AB - At the moment, there is no sensitive clinical test for detecting early-stage colorectal cancer (CRC). Target proteomics has enabled high-throughput verification of hundreds of biomarker candidate proteins. Using this technology, we verified 725 previously reported CRC biomarker candidate proteins that are functionally correlated with CRC in extracellular vesicles (EVs) from patients. Of these, 356 proteins were quantified, and 34 peptides (22 proteins) showed significant differences in the serum EVs between healthy controls and CRC patients of two independent cohorts (n = 77 and 84). These peptides were evaluated as single or multiple markers, and four single peptides in annexin family proteins and eight combinations of peptides showed area under the curve > 0.9 for discriminating between healthy controls and CRC patients. The sensitivities of annexins A3, A4, and A11 peptides for detecting early-stage CRC greatly exceed those of carcinoembryonic antigen. These peptides are promising biomarkers for early detection of CRC. PMID- 28986586 TI - Statistical analysis and a case study of tropical cyclones that trigger the onset of the South China Sea summer monsoon. AB - This paper addresses whether a tropical cyclone can trigger the onset of the South China Sea (SCS) summer monsoon (SM). We conducted a statistical analysis of tropical cyclones (TCs) generated over the western North Pacific (WNP) between late-April and May. The results showed that there were cases in which TCs were generated before the onset of the SCSSM, accounting for 43.2% of the TCs generated during this season. This study examined a representative case, Super Typhoon Chanchu (0601), which was determined to be influential in the onset of the SCSSM. With a northwestward track, Chanchu brought strong convection and westerly winds to the SCS on 12 May, which triggered the intrusion of the southwesterly winds from the Bay of Bengal and the eastward retreat of the western Pacific subtropical high. Super Typhoon Chanchu provides an example in which a TC triggered the onset of the SCSSM. The negative correlation between the onset date of the SCSSM and the number of TCs generated over the WNP used to be interpreted as the influence of the monsoon trough on TC genesis. This work provides a supplementary illustration that this relationship also includes the impact of TCs on the onset of the SCSSM. PMID- 28986587 TI - The drinking water contaminant dibromoacetonitrile delays G1-S transition and suppresses Chk1 activation at broken replication forks. AB - Chlorination of drinking water protects humans from water-born pathogens, but it also produces low concentrations of dibromoacetonitrile (DBAN), a common disinfectant by-product found in many water supply systems. DBAN is not mutagenic but causes DNA breaks and elevates sister chromatid exchange in mammalian cells. The WHO issued guidelines for DBAN after it was linked with cancer of the liver and stomach in rodents. How this haloacetonitrile promotes malignant cell transformation is unknown. Using fission yeast as a model, we report here that DBAN delays G1-S transition. DBAN does not hinder ongoing DNA replication, but specifically blocks the serine 345 phosphorylation of the DNA damage checkpoint kinase Chk1 by Rad3 (ATR) at broken replication forks. DBAN is particularly damaging for cells with defects in the lagging-strand DNA polymerase delta. This sensitivity can be explained by the dependency of pol delta mutants on Chk1 activation for survival. We conclude that DBAN targets a process or protein that acts at the start of S phase and is required for Chk1 phosphorylation. Taken together, DBAN may precipitate cancer by perturbing S phase and by blocking the Chk1-dependent response to replication fork damage. PMID- 28986588 TI - Autocrine DUSP28 signaling mediates pancreatic cancer malignancy via regulation of PDGF-A. AB - Pancreatic cancer remains one of the most deadly cancers with a grave prognosis. Despite continuous efforts to improve remedial values, limited progress has been made. We have reported that dual specificity phosphatase 28 (DUSP28) has a critical role of chemo-resistance and migration in pancreatic cancers. However, its mechanism remains unclear. Here, we further clarify the function of DUSP28 in pancreatic cancers. Analysis using a public microarray database and in vitro assay indicated a critical role of platelet derived growth factor A (PDGF-A) in pancreatic cancer malignancy. PDGF-A was positively regulated by DUSP28 expression at the mRNA and protein levels. Enhanced DUSP28 sensitized pancreatic cancer cells to exogenous PDGF-A treatment in migration, invasion, and proliferation. Transfection with siRNA targeting DUSP28 blunted the influence of administered PDGF-A by inhibition of phosphorylation of FAK, ERK1/2, and p38 signalling pathways. In addition, DUSP28 and PDGF-A formed an acquired autonomous autocrine-signaling pathway. Furthermore, targeting DUSP28 inhibited the tumor growth and migratory features through the blockade of PDGF-A expression and intracellular signaling in vivo. Our results establish novel insight into DUSP28 and PDGF-A related autonomous signaling pathway in pancreatic cancer. PMID- 28986589 TI - Post-fire carbon and nitrogen accumulation and succession in Central Siberia. AB - Improved understanding of carbon (C) accumulation after a boreal fire enables more accurate quantification of the C implications caused by potential fire regime shifts. We coupled results from a fire history study with biomass and soil sampling in a remote and little-studied region that represents a vast area of boreal taiga. We used an inventory approach based on predefined plot locations, thus avoiding problems potentially causing bias related to the standard chronosequence approach. The disadvantage of our inventory approach is that more plots are needed to expose trends. Because of this we could not expose clear trends, despite laborious sampling. We found some support for increasing C and nitrogen (N) stored in living trees and dead wood with increasing time since the previous fire or time since the previous stand-replacing fire. Surprisingly, we did not gain support for the well-established paradigm on successional patterns, beginning with angiosperms and leading, if fires are absent, to dominance of Picea. Despite the lack of clear trends in our data, we encourage fire historians and ecosystem scientists to join forces and use even larger data sets to study C accumulation since fire in the complex Eurasian boreal landscapes. PMID- 28986590 TI - Measuring molecular frequencies in the 1-10 MUm range at 11-digits accuracy. AB - High-resolution spectroscopy in the 1-10 MUm region has never been fully tackled for the lack of widely-tunable and practical light sources. Indeed, all solutions proposed thus far suffer from at least one of three issues: they are feasible only in a narrow spectral range; the power available for spectroscopy is limited; the frequency accuracy is poor. Here, we present a setup for high-resolution spectroscopy, whose approach can be applied in the whole 1-10 MUm range. It combines the power of quantum cascade lasers (QCLs) and the accuracy achievable by difference frequency generation using an orientation patterned GaP crystal. The frequency is measured against a primary frequency standard using the Italian metrological fibre link network. We demonstrate the performance of the setup by measuring a vibrational transition in a highly-excited metastable state of CO around 6 MUm with 11 digits of precision. PMID- 28986591 TI - Role of Oceanic and Terrestrial Atmospheric Moisture Sources in Intraseasonal Variability of Indian Summer Monsoon Rainfall. AB - Summer Monsoon Rainfall over the Indian subcontinent displays a prominent variability at intraseasonal timescales with 10-60 day periods of high and low rainfall, known as active and break periods, respectively. Here, we study moisture transport from the oceanic and terrestrial sources to the Indian landmass at intraseasonal timescales using a dynamic recycling model, based on a Lagrangian trajectory approach applied to the ECMWF-ERA-interim reanalysis data. Intraseasonal variation of monsoon rainfall is associated with both a north-south pattern from the Indian landmass to the Indian Ocean and an east-west pattern from the Core Monsoon Zone (CMZ) to eastern India. We find that the oceanic sources of moisture, namely western and central Indian Oceans (WIO and CIO) contribute to the former, while the major terrestrial source, Ganga basin (GB) contributes to the latter. The formation of the monsoon trough over Indo-Gangetic plain during the active periods results in a high moisture transport from the Bay of Bengal and GB into the CMZ in addition to the existing southwesterly jet from WIO and CIO. Our results indicate the need for the correct representation of both oceanic and terrestrial sources of moisture in models for simulating the intraseasonal variability of the monsoon. PMID- 28986593 TI - Effect of Body Position on Epsicleral Venous Pressure in Healthy Subjects. AB - Purpose: The mechanism of IOP change during a body position change is poorly understood. In this study, we investigated changes in episcleral venous pressure (EVP) between two body positions, sitting and inclined, and compared this with changes in IOP. Methods: This study was a prospective, comparative case series of 43 eyes of 24 healthy volunteers. IOP was measured using a pneumatonometer in the seated position. EVP was then measured in a selected episcleral vein by using an automated, slit-lamp-mounted venomanometer. Thirty minutes later, the subject was placed in an inclined position with the neck extended and the head resting on the chin rest of the slit lamp. After 5 minutes, IOP and EVP in the same vein were remeasured. EVP in the inclined position was compared with EVP in the seated position, and the change in IOP was compared with the change in EVP. Statistical significance was determined using generalized estimating equation models. Results: Mean IOP increased from 11.4 +/- 3.0 mm Hg (mean +/- SD) in the sitting position to 13.1 +/- 3.4 mm Hg in the inclined position (P < 0.001). Mean EVP increased from 6.4 +/- 1.4 mm Hg in the sitting position to 7.8 +/- 1.7 mm Hg in the inclined position (P < 0.001). The postural rise in IOP was not different from the rise in EVP (P = 0.18). Conclusions: In the inclined position, IOP and EVP are higher than they are in the sitting position. The posture-induced rise in IOP can be attributed to an increase in EVP. PMID- 28986592 TI - Sustaining Intravitreal Residence With L-Arginine Peptide-Conjugated Nanocarriers. AB - Purpose: Intravitreal injection of antiangiogenic agents is becoming a standard treatment for neovascular retinal diseases. Sustained release of therapeutics by injecting colloidal carriers is a promising approach to reduce the injection frequency, which reduces treatment burdens and the risk of complications on patients. Such sustained release often requires carriers to have micrometer-scale dimension that, however, can potentially promote glaucoma and inflammation. Small, polycationic particles can be immobilized in vitreous through multiple cooperative ionic interactions with hyaluronic acid of the vitreous interior, but such particles are generally toxic. Here, we synthesized and examined a biocompatible dextran-based nanocarrier (<50 nm in diameter) conjugated with cationic peptides containing L-arginine with minimal toxicity, aiming to provide sustained release of therapeutic drugs in vitreous. Methods: We synthesized the nanocarriers with condensed cholesteryl dextran (CDEX) as core material. Cationic peptides containing 1 to 4 arginine groups, along with fluorescence tags, were conjugated to the CDEX surface. We monitored the carrier diffusion rate ex vivo and half-lives in vivo in rodent vitreous using fluorescence imaging. We evaluated the toxicity by histological examinations at the second, third, eighth, and thirty-sixth week. Results: The diffusion rate of nanocarriers was inversely related to zeta potential values in freshly isolated vitreous humor. We observed increased half-lives in vivo with increasing zeta potential (up to 240 days). Histological examinations confirmed no adverse effects on ocular morphology and organization. Conclusions: We demonstrated the potential of L-arginine peptide conjugated nanocarriers toward safe and sustained therapeutic release system for posterior eye diseases. PMID- 28986594 TI - Plateau Iris Distribution Across Anterior Segment Optical Coherence Tomography Defined Subgroups of Subjects With Primary Angle Closure Glaucoma. AB - Purpose: We previously identified three distinct subgroups of patients with primary angle closure glaucoma (PACG) based on anterior segment optical coherence tomography (ASOCT) imaging. Group 1 was characterized by a large iris area with deepest anterior chambers, group 2 by a large lens vault (LV) and shallow anterior chamber depth (ACD), and group 3 displayed intermediate values across iris area, LV, and ACD. The purpose of the present study was to determine the distribution of plateau iris in these subgroups using ultrasound biomicroscopy (UBM) features. Methods: UBM images of the 210 subjects who were previously enrolled for the ASOCT subgrouping analysis and had undergone laser peripheral iridotomy were assessed and graded by a single glaucoma fellowship trained clinician. Plateau iris was defined as the presence of all the following UBM criteria in at least two quadrants: anteriorly directed ciliary body, absent ciliary sulcus, iris angulation, flat iris plane, and iridoangle touch. Results: Of 210 subjects, 23 were excluded due to poor-quality images. Based on standardized UBM criteria, the overall prevalence of plateau iris was 36.9% (n = 187). The proportion of plateau iris was similar across the three groups (subgroup 1:35.4% (n = 29); subgroup 2:39.0% (n = 32); subgroup 3:34.8% (n = 8), P = 0.87). On multiple logistic regression analysis, iris thickness at 750 MUm from the scleral spur (IT750) was the only variable associated with plateau iris (odds ratio: 1.5/100 MUm increase in iris thickness [IT], P = 0.04). Conclusions: The proportion of plateau iris was similar across the three ASOCT-based PACG subgroups and more than one-third of subjects with PACG were diagnosed with plateau iris based on standardized UBM criteria. In addition, we noted that eyes with increased peripheral IT have an increased likelihood of plateau iris. PMID- 28986595 TI - Comparison of Neovascular Lesion Area Measurements From Different Swept-Source OCT Angiographic Scan Patterns in Age-Related Macular Degeneration. AB - Purpose: We compared area measurements for the same neovascular lesions imaged using swept source optical coherence tomography angiography (SS-OCTA) and enlarging scan patterns. Methods: Patients with neovascular age-related macular degeneration were imaged using a 100-kHz SS-OCTA instrument (PLEX Elite 9000). The scanning protocols included the 3 * 3, 6 * 6, 9 * 9, and 12 * 12 mm fields of view. Two groups were studied. Group 1 included small lesions contained within the 3 ?( ?times ?) 3 mm scan, and Group 2 included larger lesions that were fully contained within the 6 ?( ?times ?) 6 mm scan. Results: A total of 30 eyes of 26 patients were enrolled in Group 1 and 30 eyes of 25 patients were enrolled in Group 2. In Group 1, the automated mean lesion area measurements were 1.11 (SD = 0.78), 1.14 (SD = 0.80), and 1.27 (SD = 0.82) mm2 for the 3 ?( ?times ?) 3, 6 ?( ?times ?) 6, and 12 ?( ?times ?) 12 mm scans, respectively (ANOVA P < 0.001; post hoc comparisons, P = 0.184, 3 ?( ?times ?) 3 vs. 6 ?( ?times ?) 6 mm; P < 0.001 for the other two pairs). In Group 2, the automated mean lesion area measurements were 5.43 (SD = 2.56), 5.53 (SD = 2.48), and 5.49 (SD = 2.65) mm2 for the 6 ?( ?times ?) 6, 9 ?( ?times ?) 9, and 12 ?( ?times ?) 12 mm scans, respectively (ANOVA P = 0.435; post-hoc comparisons, P = 0.062, 6 ?( ?times ?) 6 vs. 9 ?( ?times ?) 9 mm; P = 0.553, 6 ?( ?times ?) 6 vs. 12 ?( ?times ?) 12 mm; P = 0.654, 9 ?( ?times ?) 9 vs. 12 ?( ?times ?) 12 mm). Conclusions: The similarity in lesion area measurements across different scan patterns suggests that SS-OCTA imaging can be used to follow quantitatively the enlargement of choroidal neovascularization as the disease progresses. PMID- 28986596 TI - Palisade Endings of Extraocular Muscles Develop Postnatally Following Different Time Courses. AB - Purpose: To analyze in a frontal-eyed mammal (cat) the postnatal development of palisade endings in extraocular muscles (EOMs) and to compare the spatiotemporal and quantitative patterns of palisade endings among individual rectus muscles. Methods: Cats of different ages ranging from birth to adult stage were studied. EOM whole-mount preparations were fluorescently labeled using six combinations of triple staining and analyzed in the confocal laser scanning microscope. Results: Palisade endings developed postnatally and passed in each rectus muscle through the same, three developmental steps but in a heterochronic sequence and to a different final density per muscle. Specifically, palisade ending development was first completed in the medial rectus and later in the inferior, lateral, and superior rectus. The highest density of palisade endings was observed in the medial rectus and the lowest in the lateral rectus whereas values for the inferior and superior rectus were in between. Palisade endings expressed high levels of growth associated protein 43 during development and were supplied by axons that established motor terminals. Conclusions: Cats open their eyes 7 to 10 days after birth and later develop a complex three-dimensional visuomotor climbing and jumping behavior depending on accurate binocular vision and fine tuning of the ocular movements. Our findings indicate that palisade ending development correlates with important landmarks in visuomotor behavior and provide support for our previous notion that palisade endings play an important role for convergence eye movements in frontal-eyed species. PMID- 28986597 TI - Associations Between Outer Retinal Structures and Focal Macular Electroretinograms in Patients With Retinitis Pigmentosa. AB - Purpose: Our earlier study showed that the width of the intact ellipsoid zone (EZ) of the photoreceptors was significantly but weakly correlated with the amplitudes of the focal macular ERGs (FMERGs). The aim of this study was to determine a microstructure of the photoreceptors in the spectral-domain optical coherence tomographic (SD-OCT) images that was more strongly correlated with the FMERG parameters in eyes with retinitis pigmentosa (RP). Methods: This was a retrospective, observational study. The medical records of 65 patients with RP were reviewed. FMERGs were elicited by a 15-degree stimulus spot. The width of the EZ and the outer segment (OS) area surrounded by EZ and retinal pigment epithelium in the SD-OCT images within 15 degrees of the fovea were evaluated. Spearman correlation tests and multiple stepwise regression analyses were performed. Results: There was a strong correlation between the amplitudes of FMERGs and the EZ width (r = 0.68 for a-wave amplitude; r = 0.64 for b-wave amplitude), and also between the amplitudes of the FMERGs and the OS area (r = 0.69 for a-wave amplitude; r = 0.67 for b-wave amplitude). However, some patients had long EZ widths but had severely reduced FMERGs. Multiple stepwise regression analyses showed that the OS area was the only significant independent predictor of the amplitudes of FMERGs (P < 0.001). Conclusions: The OS area might be a better morphological structure to use to predict the physiological function of the macula. PMID- 28986598 TI - Hydrogen Sulfide Protects Retinal Ganglion Cells Against Glaucomatous Injury In Vitro and In Vivo. AB - Purpose: Hydrogen sulfide (H2S) is recognized as a novel third signaling molecule and gaseous neurotransmitter. Recently, cell protective properties within the central nervous and cardiovascular system have been proposed. Our purpose was to analyze the expression and neuroprotective effects of H2S in experimental models of glaucoma. Methods: Elevated IOP was induced in Sprague-Dawley rats by means of episcleral vein cauterization. After 7 weeks, animals were killed and the retina was analyzed with label-free mass spectrometry. In vitro, retinal explants were exposed to elevated hydrostatic pressure or oxidative stress (H2O2), with and without addition of a slow-releasing H2S donor Morpholin-4-ium-methoxyphenyl morpholino-phosphinodithioate (GYY4137). In vivo, GYY4137 was injected intravitreally in animals with acute ischemic injury or optic nerve crush. Brn3a+ retinal ganglion cells (RGCs) were counted in retinal flat mounts and compared. Optical coherence tomography (OCT) was performed to examine the vessels. Comparisons were made by t-test and ANOVA (P < 0.05). Results: IOP elevation caused significant RGC loss (P < 0.001); 3-mercaptosulfurtransferase, an H2S producing enzyme, showed a 3-fold upregulation within the retina after IOP elevation. GYY4137 protected RGCs against elevated pressure and oxidative stress in vitro depending on the concentration used (P < 0.005). In vivo, intravitreal administration of GYY4137 preserved RGCs from acute ischemic injury and optic nerve crush (P < 0.0001). Retinal vessel diameters enlarged after intravitreal GYY4137 injection (P < 0.0001). Conclusions: H2S is specifically regulated in experimental glaucoma. By scavenging reactive oxygen species and dilating retinal vessels, H2S may protect RGCs from pressure and oxidative stress-induced RGC loss in vitro and in vivo. Therefore, H2S might be a novel neuroprotectant in glaucoma. PMID- 28986599 TI - Use of Firearms in Terrorist Attacks: Differences Between the United States, Canada, Europe, Australia, and New Zealand. PMID- 28986600 TI - ? PMID- 28986601 TI - Microbiome-health interactions in older people. AB - Alterations in the composition and function of the gut microbiome have been implicated in a range of conditions and diseases. Culture-dependent and culture independent studies both showed that older people harbour a gut microbiome that differs in composition from that of younger adults. Detailed analyses have identified discrete microbiota subtypes that characterize intermediates between a high diversity microbiota found in healthy community-dwelling subjects and a low diversity microbiota typical for elderly living in long-term residential care. There are also alterations in the microbiome composition associated with biological age, independent of health status. Even after adjusting for confounding factors such as age and medication, trends in microbiota composition correlate with gradients in clinical metadata particularly frailty and inflammatory status. There are few known mechanisms by which these associations might be causative rather than consequential, and this is a subject of intensive research. The strongest candidate effectors are microbial metabolites that could impact host energy balance, act as signalling molecules to modulate host metabolism or inflammation, and potentially also impact on the gut-brain axis. PMID- 28986603 TI - ? PMID- 28986602 TI - Selected aspects of the human gut microbiota. AB - The gut microbiota represents a highly complex assembly of microbes, which interact with each other and with their host. These interactions have various implications in terms of health and disease, and this multi-author review issue will address a number of selected aspects pertaining to gut microbiota research. PMID- 28986604 TI - Erratum to: Cognitive and mood improvements following acute supplementation with purple grape juice in healthy young adults. AB - In the original publication of the article, on page 7, paragraph "Discussion", line 12, 'blackcurrant has been observed to increase digit vigilance reaction time' should read as 'blackcurrant has been observed to decrease digit vigilance reaction time'. PMID- 28986605 TI - [Speech audiometry and data logging in CI patients : Implications for adequate test levels. German version]. AB - BACKGROUND: As part of postoperative cochlear implant (CI) diagnostics, speech comprehension tests are performed to monitor audiological outcome. In recent years, a trend toward improved suprathreshold speech intelligibility in quiet and an extension of intelligibility to softer sounds has been observed. Parallel to audiometric data, analysis of the patients' acoustic environment can take place by means of data logging in modern CI systems. OBJECTIVES: Which test levels reflect the individual listening environment in a relevant manner and how can these be reflected in a clinical audiometric setting? PATIENTS AND METHODS: In a retrospective analysis, data logs of 263 adult CI patients were evaluated for sound level and the listening situation (quiet, speech in quiet, noise, speech in noise, music, and wind). Additionally, monosyllabic word comprehension in quiet was analyzed in experienced CI users at presentation levels of 40-80 dB. RESULTS: For the sound level in the acoustic environment of postlingually deafened adult CI users, data logging shows a maximum occurrence of speech signals in the range 50-59 dB. This demonstrates the relevance of everyday speech comprehension at levels below 60 dB. CONCLUSIONS: Individual optimization of speech intelligibility with a CI speech processor should not be performed in the range of 65-70 dB only, but also at lower levels. Measurements at 50 dB currently seem to be a useful addition. PMID- 28986606 TI - Effect of breviscapine on CYP3A metabolic activity in healthy volunteers. AB - OBJECTIVE: The purpose of this study was to investigate the influence of breviscapine on the pharmacokinetics of concomitantly administered midazolam (MID) and its associations with and effects on genetic polymorphism of the gene encoding cytochrome P450 3A5 (CYP3A5) in healthy volunteers. METHODS: The study group comprised 17 healthy volunteers who had been genotyped for CYP3A5*3 prior to start of the study. These volunteers were given daily doses of 120 mg (40 mg, three times a day) of breviscapine or a placebo for 14 days, followed by 7.5 mg midazolam (MID) on day 15. The plasma concentrations of MID and the metabolite 1 hydroxy-midazolam (1-OH-MID) were determined by ultra-performance liquid chromatography-mass spectrometry for up to 12 h after drug administration. RESULTS: The pharmacokinetics of MID and 1-OH-MID were significantly different between the breviscapine and placebo groups, with a point estimate for MID AUC(0 12) of 1.56 (90% confidence interval 1.26, 1.87). The pharmacokinetics of MID and 1-OH-MID were not different among the CYP3A5 genotype groups, regardless of whether MID was coadministered with breviscapine or with placebo. CONCLUSIONS: These findings suggest that breviscapine inhibited the metabolism of CYP3A in the volunteers, with no interaction difference among the different CYP3A5 genotypes. PMID- 28986607 TI - Administrative health data: guilty until proven innocent. Response to comments by Levy and Sobolev. PMID- 28986610 TI - Meta-analysis of hypertension and osteoporotic fracture risk in women and men: response to comments by Rodriguez et al. PMID- 28986608 TI - Opiate dependence induces cell type-specific plasticity of intrinsic membrane properties in the rat juxtacapsular bed nucleus of stria terminalis (jcBNST). AB - RATIONALE: Drugs of abuse can alter circuit dynamics by modifying synaptic efficacy and/or the intrinsic membrane properties of neurons. The juxtacapsular subdivision of the bed nucleus of stria terminalis (jcBNST) has unique connectivity that positions it to integrate cortical and amygdala inputs and provide feed-forward inhibition to the central nucleus of the amygdala (CeA), among other regions. In this study, we investigated changes in the synaptic and intrinsic properties of neurons in the rat jcBNST during protracted withdrawal from morphine dependence using a combination of conventional electrophysiological methods and the dynamic clamp technique. RESULTS: A history of opiate dependence induced a form of cell type-specific plasticity characterized by reduced inward rectification associated with more depolarized resting membrane potentials and increased membrane resistance. This cell type also showed a lower rheobase when stimulated with direct current (DC) pulses as well as a decreased firing threshold under simulated synaptic bombardment with the dynamic clamp. Morphine dependence also decreased excitatory postsynaptic potential amplification, suggesting the downregulation of the persistent Na+ current (I NaP). CONCLUSION: These findings show that a history of morphine dependence leads to persistent cell type-specific plasticity of the passive membrane properties of a jcBNST neuronal population, leading to an overall increased excitability of such neurons. By altering the activity of extended amygdala circuits where they are embedded, changes in the integration properties of jcBNST neurons may contribute to emotional dysregulation associated with drug dependence and withdrawal. PMID- 28986611 TI - Comments on Li et al.: Meta-analysis of hypertension and osteoporotic fracture risk in women and men. PMID- 28986609 TI - Comparison of effect of an increased dosage of vonoprazan versus vonoprazan plus lafutidine on gastric acid inhibition and serum gastrin. AB - BACKGROUND: Vonoprazan, a novel potassium-competitive acid blocker, elicits potent acid inhibition and hypergastrinemia at a dose of 20 mg. Its recommended maintenance dose for gastro-esophageal reflux disease is 10 mg, which is sometimes insufficient for preventing nocturnal acid breakthrough (NAB). Concomitant use of a histamine 2 receptor antagonist (H2RA) is effective for NAB. However, further acid inhibition by addition of H2RA has concern of hypergastrinemia again. Lafutidine (H2RA) is known to stimulate somatostatin release. AIMS: The aim of this study is to compare the levels of acid inhibition and serum gastrin attained by addition of lafutidine to vonoprazan 10 mg with levels after a dose increase of vonoprazan from 10 to 20 mg. METHODS: Thirteen healthy volunteers underwent 24-h intragastric pH monitoring and serum gastrin measurements on day 7 of three different regimens: vonoprazan 10 mg, vonoprazan 10 mg plus lafutidine 10 mg, and vonoprazan 20 mg. RESULTS: Median pH 4 holding time ratios (range) by vonoprazan 10 mg, vonoprazan 10 mg plus lafutidine 10 mg, and vonoprazan 20 mg were 82% (47-88%), 88% (76-93%), and 99% (95-100%) while those at nighttime from 10 p.m. to 8 a.m. were 94% (29-100%), 100% (95-100%), and 100%, respectively. The incidences of NAB with vonoprazan 10 mg, vonoprazan plus lafutidine, and vonoprazan 20 mg were 38, 8, and 0%, respectively. Respective serum gastrin levels were 420 (173-508), 323 (196-521), and 504 (400-812) pg/ml. CONCLUSION: Addition of lafutidine 10 mg to vonoprazan 10 mg achieved sufficient acid inhibition, especially at nighttime, without further increase of serum gastrin levels. PMID- 28986613 TI - Administrative health data: guilty until proven innocent. PMID- 28986612 TI - [Imaging of locally advanced prostate cancer : Importance of ultrasound and especially MRI]. AB - Prostate cancer is the most common male malignant tumor in Germany, which thus places growing demands on differentiated imaging and risk-adapted therapeutic approaches. Multiparametric MRI (mpMRI) of the prostate enables reliable detection of clinically significant cancers and is currently the leading imaging modality for the detection, characterization, and local staging of prostate cancer. According to the German S3 guideline, mpMRI of the prostate is currently primarily recommended in patients with previous negative TRUS biopsies and persisting tumor suspicion. The serial use of mpMRI in the pretherapeutic setting can support individual therapy planning of patients with locally advanced prostate cancer in the near future. PMID- 28986614 TI - Clinical and angiographic outcomes in patients with intracranial aneurysms treated with the pipeline embolization device: intra-procedural technical difficulties, major morbidity, and neurological mortality decrease significantly with increased operator experience in device deployment and patient management. AB - PURPOSE: Flow diversion constitutes a pivotal advancement in endovascular intracranial aneurysm treatment, but requires development of a new skill set. The aim of this study is to determine whether outcomes after treatment with the Pipeline Embolization Device improve with experience. METHODS: We retrospectively reviewed all patients with intracranial aneurysms treated with Pipeline at two centers over a 4.5-year period. Baseline patient and aneurysm characteristics, complications, and angiographic outcomes were analyzed. RESULTS: One hundred forty patients underwent 150 Pipeline procedures to treat 167 intracranial aneurysms during the study period, 109 women, mean age 55.4 years. One hundred twenty-six aneurysms were ICA, mean size 10.2 mm and mean neck 6.4 mm. Intra procedural technical difficulties were higher during the first 75 procedures compared with the subsequent 75 (13.3 vs 2.7%; p = 0.03), as combined major morbidity and neurological mortality (14.7 vs 4%; p = 0.046). In multivariate regression analysis, increased operator experience with Pipeline remained an independent predictor of intra-procedural technical difficulties (p = 0.02, odds ratio (OR) 0.015, 95% CI 0.0004-0.55) and combined major morbidity and neurological mortality (p = 0.03, OR 0.16, 95% CI 0.03-0.84). At last follow-up, 123 aneurysms were completely occluded (81.5%, mean 24 months). In our cohort, age <= 53 years was an independent predictor of complete aneurysm occlusion at last follow-up (p = 0.001, OR 0.92, 95% CI 0.88-0.97). Five aneurysms were retreated (3.3%). CONCLUSION: The Pipeline embolization device is an effective treatment for intracranial aneurysms. The risk of intra-procedural technical difficulties and combined major morbidity and neurological mortality decreases significantly with increased operator experience in Pipeline deployment and patient management. PMID- 28986615 TI - Perforations associated with peripherally inserted central catheters in a neonatal population. AB - BACKGROUND: Peripherally inserted central catheters (PICCs) are increasingly used in neonates but perforations can result in devastating complications such as pericardial and pleural effusions. Identifying risk factors may guide surveillance and reduce morbidity and mortality. OBJECTIVE: To determine the risk factors for PICC perforation in neonates. MATERIALS AND METHODS: Retrospective case:control (1:2) study of neonates admitted between 2004-2014. Charts and imaging were reviewed for clinical and therapeutic risk factors. RESULTS: Among 3,454 PICCs, 15 cases of perforation (incidence 0.4%, 5 pericardial effusions, 10 pleural effusions) were matched to 30 controls, based on gestation and insertion date. Timing of perforations post-insertion was median 4 days for pericardial effusions and 21.5 days for pleural effusions. A risk factor for pericardial effusion was lower weight at PICC insertion compared with controls. There were no statistically significant differences between cases and controls in catheter material, insertion site, PICC size and lumen number. Among upper limb PICCs, pericardial effusions were associated with tip positions more proximal to the heart at insertion (P=0.005) and at perforation (P=0.008), compared with controls. Pleural effusions were associated with tip positions more distal from the heart at perforation (P=0.008). Within 48 h before perforation, high/medium risk infusions included total parenteral nutrition (100% cases vs. 56.7% controls, P=0.002) and vancomycin (60% cases vs. 23.3% controls, P=0.02). CONCLUSION: PICC-associated pericardial effusions and pleural effusions are rare but inherent risks and can occur at any time after insertion. Risk factors and etiologies are multifactorial, but PICC tip position may be a modifiable risk factor. To mitigate this risk, we have developed and disseminated guidelines for target PICC positions and routinely do radiographs to monitor PICCs for migration and malposition in our NICU. The increased knowledge of risk profiles from this study has helped focus surveillance efforts and facilitate early recognition and treatment. PMID- 28986616 TI - Hysteropreservation versus hysterectomy in the surgical treatment of uterine prolapse: systematic review and meta-analyses. PMID- 28986617 TI - Risk of fracture of the acromion depends on size and orientation of acromial bone tunnels when performing acromioclavicular reconstruction. AB - PURPOSE: Current techniques for anatomic repair of the dislocated acromioclavicular (AC) joint aim on reconstruction of the AC ligaments and utilize tunnels drilled through the acromion . This improves the stability of the reconstruction but might also increase the risk of fractures at the acromion. The purpose of this study was to evaluate the fracture risk for the acromion after transacromial tunnel placement for anatomic AC joint stabilization procedure. It was hypothesized that the risk of fracture of the acromion is correlated to size and orientation of bone tunnels commonly used for anatomic AC joint reconstruction. METHODS: A finite element analysis was used to simulate multiple bone tunnels and incoming force vectors (lateral vs. superior). Different tunnels were analysed, horizontal meaning an anterior-posterior orientation versus a vertical inferior-superior orientation through the acromion. Two tunnel diameters were simulated (2.4 vs. 4.5 mm). Furthermore, the tunnel length and distance between tunnels were altered. Forty-five cadaveric specimens (median age: 64 years, range 33-71 years) were utilized for data acquisition. Out of these, 30 specimens were used to evaluate basic tunnel orientations and drill diameters using a MTS 858 servohydraulic test system. RESULTS: With regard to the tunnel orientation and drill hole size, the loads to failure were limited. The acromion is at higher fracture risk, with a superior to inferior directed incoming force. Position, size and direction of bone tunnels influenced the loads to failure. Horizontal tunnels with a higher diameter (4.5 mm) had the most impact on load to failure reduction. A long horizontal tunnel with a diameter of 4.5 mm reduced the load to failure with medial direction of force to 25% of the native acromion. The identical tunnel with a diameter of 2.4 mm reduced the load to failure to 61%. Both 2.4-mm horizontal tunnels with a medium and short length did not reduce the load to failure. CONCLUSION: Tunnels placed at the acromion did not result in an increased risk of fracture. However, descriptive data showed a tendency for an increased fracture risk if tunnels are placed at the acromion, especially in horizontal direction with diameters of 4.5 mm. In addition, the pattern of fracture was dependent on the orientation of the bone tunnels and the size. However, the results indicate a "safe zone" for the placement of bone tunnels within the anterior half of the acromion, which does not affect the loads to failure at the acromion. Therefore, current techniques for anatomic AC joint reconstruction which utilize fixation of grafts or sutures at the acromion are safe within current ranges of tunnel placement and sizes. PMID- 28986618 TI - [177Lu-PSMA therapy : Current evidence for use in the treatment of patients with metastatic prostate cancer]. AB - BACKGROUND: Despite significant progress in the treatment of metastatic castration-resistant prostate cancer (mCRPC) in recent years (including agents targeting androgen receptor signaling, chemotherapy, and 223Ra), most of these patients still succumb to prostate cancer. Recently, 177lutetium prostate specific membrane antigen radioligand therapy (177Lu-PSMA-RLT) has been increasingly used within compassionate use provisions in these patients in Germany and showed promising efficacy. OBJECTIVES: Establishment of the current position of 177Lu-PSMA-RLT in mCRPC in 2017. MATERIALS AND METHODS: Presentation of the therapy landscape in mCRPC and the current challenges within treatment and survey of the available data on 177Lu-PSMA-RLT after PubMed-based research. RESULTS: In several larger retrospective studies, 177Lu-PSMA-RLT seems to be an encouraging new option with the potential to extend overall survival while displaying a favorable toxicity profile. CONCLUSIONS: Prospective trials are urgently needed to confirm these encouraging results found in retrospective analyses with 177Lu-PSMA-RLT in the treatment of mCRPC. PMID- 28986619 TI - [Therapeutic utilization of stem cells in orthopedics]. AB - Stem cells are becoming increasingly more important in the field of regenerative medicine. Adult mesenchymal stem cells (MSCs) are harvested predominantly from bone marrow or adipose tissue, are already being used in the clinical setting and have a low potential for side effects. In orthopedics, experience has been gained in the treatment of bone defects, non-unions, cartilage defects, osteoarthritis and tendon pathologies. The current data are derived from case studies and randomized controlled trials are missing; therefore, there are many open questions concerning the optimal cell source, number of cells, administration technique (e.g. injections and matrices) or combinations with growth factors; however, it is evident from the data that MSCs have a positive effect on tissue regeneration and are safe to use. PMID- 28986620 TI - [Imaging of primary muscular diseases : What do neurologists expect from radiologists?] AB - Imaging, in particular magnetic resonance imaging (MRI), has in recent years increasingly become a crucial tool for the diagnostics of inherited and acquired muscular diseases. The aim of imaging in neuromuscular disorders goes beyond the detection and quantification of degenerative muscular changes, such as fatty degeneration and includes recognition of very early signs of muscular pathologies presenting as muscular edema. Therefore, imaging is a valuable diagnostic method to support the clinical diagnosis and to narrow down the differential diagnoses, leading to specific additional diagnostic tests in order to establish the correct diagnosis. Although advances in MRI hardware and technology have led to a faster, more accurate and advanced image acquisition allowing whole body examination in a feasible fashion, the standardization of image acquisition and interpretation remains a challenge. The aim of this review article is to address the important and clinically relevant issues concerning the role of imaging of neuromuscular diseases in order to facilitate a good interdisciplinary management for the diagnostics and monitoring of neuromuscular diseases. PMID- 28986622 TI - Defensins defend against bone loss. PMID- 28986621 TI - Modification of the Surgical Strategy for the Dissection of the Recurrent Laryngeal Nerve Using Continuous Intraoperative Nerve Monitoring. AB - BACKGROUND: The aim of this study was to describe first experiences and changes in management using continuous intraoperative neuromonitoring (C-IONM) in thyroid and parathyroid surgery. METHOD: Retrospective analysis of patients who underwent surgery with C-IONM since 2012. Surgical maneuvers were modified when electrophysiologic events occurred. Patients with persistent loss of signal (LOS) underwent postoperative laryngoscopy. RESULTS: One hundred and one patients (of 1586 neck surgeries) were included and 19 had events: In 13 these were temporary (resolved before end of surgery) and led to intraoperative modifications in surgical approach; in all cases traction was released, and in 8, recurrent laryngeal nerve (RLN) approach was changed [superior approach (2), inferior approach (2), both (4)]. Six patients had persistent LOS (5.9%, present at end of procedure), with RLN palsy (RLNP) on postoperative day 1: In three, LOS occurred at electrode placement on the vagus nerve, leading to distal placement of the electrode allowing ipsilateral dissection under continuous monitoring; all three had complete recovery at 6 months. In the three other patients, LOS occurred on the RLN: one probable thermal, one traction lesion and one accidental section of the anterior RLN branch. The RLN recovered within 6 months in two patients, and in the third, RLNP persisted after 6 months (1/101 = 1%). CONCLUSION: C-IONM provides real-time evaluation of the RLN function, allowing for adaptation of surgical maneuvers to prevent RLNP. It seems particularly useful in difficult cases like redo neck surgery, invasive thyroid cancer and intrathoracic or large goiter. Care should be given at electrode placement on the vagus nerve. PMID- 28986623 TI - [Health-related quality of life after implantation of a keratoprosthesis with biological haptic]. AB - BACKGROUND: Many studies report comparatively good long-term results among patients with keratoprostheses with biological haptic. However, overall costs are correspondingly high. A clear cost-benefit relationship is therefore desirable. OBJECTIVE: This study investigates health-related quality of life after implantation of a keratoprosthesis with biological haptic. MATERIALS AND METHODS: We present a retrospective analysis of medical data of 25 patients treated between 1996 and 2006 at the Department of Ophthalmology, University Hospital Homburg/Saar and the Klinikum Offenburg. Health-related quality of life was assessed by means of a questionnaire based on validated instruments, with particular emphasis on physical symptoms, mental health, functional limitations, and social interactions. RESULTS: At a patient age of 49.8 +/- 15.7 years (minimum-maximum: 19-78 years; 6 female, 19 male), the mean duration of corneal blindness was 13.8 +/- 13.1 years (minimum-maximum: 1-47 years). Changes in visual acuity and subjective satisfaction were statistically significant (p <0.001). Quality of life (on a scale of 1 to 6: median 2) at the time "before the onset of eye disease" and >=15 months after surgery were identical. Patients with a postoperative visual acuity <=0.1 (n =11) also showed a statistically significant (p =0.016) benefit in this context. CONCLUSION: The expenditures and costs of keratoprosthetics can be justified by an improvement in the health related quality of life of the persons concerned. Even a postoperative visual acuity of <=0.1 correlates with a statistically significant improvement in the subjective quality of life of these patients. PMID- 28986624 TI - Significant changes of T2 value in the peripheral zone and seminal vesicles after ejaculation. AB - OBJECTIVES: To analyse the quantitative changes of the prostate and seminal vesicles (SV) on magnetic resonance imaging (MRI) after ejaculation. METHODS: Ten healthy young males were enrolled for T2-weighted and T2 mapping MRI before and after two consecutive ejaculations. T2 values of the peripheral zone (PZ) and the central gland (CG) at the midgland of the prostate were compared before and after ejaculation, respectively. T2 values of the PZ at the apex and base were also compared before and after, respectively. Pre- and post-ejaculation SV volumes were compared. The Wilcoxon's signed rank test with Bonferroni adjustment was used for comparison. RESULTS: After ejaculation, T2 values of the PZ significantly decreased (mean, 119+/-20 vs. 105+/-21, p=0.002) while those of the CG did not significantly change at the midgland. At the apex, T2 values of the PZ also decreased significantly (mean, 114+/-9 vs. 94+/-7, p=0.002). On the other hand, T2 values of the PZ did not change at the base. SV volumes were significantly reduced after ejaculation (mean, 11.1+/-7.7mL vs. 7.2+/-6.7mL, p=0.002). CONCLUSIONS: Ejaculation decreases T2 values of the PZ at the midgland and apex, and reduces SV volumes. Abstinence periods should be considered in evaluating the prostate and SV on MRI. KEY POINTS: * T2 values decrease after ejaculation in the apical-mid peripheral zone. * Ejaculation does not affect T2 values of the central gland. * Volume of the seminal vesicles decreases after ejaculation. * An abstinence period should be considered before pelvic MRI in men. PMID- 28986625 TI - [Opinion of the BVA and the DOG on physical therapy of dry eye : July 2017 status]. PMID- 28986626 TI - Results of transurethral resection of the prostate in renal transplant recipients: a single center experience. AB - OBJECTIVES: The aim of this study was to retrospectively evaluate the early and long-term results of renal transplantation (RT) patients undergoing transurethral resection of the prostate (TURP) due to benign prostate hyperplasia (BPH). MATERIALS AND METHODS: Eighty-nine patients with RT performed in our hospital underwent TURP between November 2008 and March 2016. Results were evaluated along with early and long-term complications. Patients were followed up for a minimum of 12 months. RESULTS: The mean age of the patients was 61.4 +/- 7.4 years. The median duration of dialysis was 28 (0-180) months. The median duration between transplantation and TURP was 13 (0-84) months. Before TURP, the mean serum creatinine (sCr) was 1.99 +/- 0.83 mg/dL and the mean prostate volume was 33.3 +/ 14.6 cm3. The mean Q max, Q ave and PVR values were 9.5 +/- 3.7, 5.2 +/- 2.2 ml/s and 85(5-480) mL, respectively. None of the patients developed perioperative and postoperative major complications. Twelve patients (13.4%) developed urinary tract infections in the postoperative period. The sCr, IPSS and PVR values significantly decreased, while Q max and Q ave significantly increased at the 1 month follow-up. At the 6-month follow-up, 63 (70.8%) patients had retrograde ejaculation. Patients were followed up for a median of 42 (12-96) months. Three patients (3.3%) were re-operated for bladder neck contracture and eight (8.9%) patients were re-operated for urethral stricture. CONCLUSION: TURP can be safely and successfully applied for the treatment of BPH after RT. LUTS and renal functions significantly improve after the operation. Patients should be followed up for UTIs in the short term and for urethral stricture in the long term. PMID- 28986627 TI - Linkage between the I-3 gene for resistance to Fusarium wilt race 3 and increased sensitivity to bacterial spot in tomato. AB - KEY MESSAGE: The negative association between the I - 3 gene and increased sensitivity to bacterial spot is due to linkage drag (not pleiotropy) and may be remedied by reducing the introgression size. Fusarium wilt is one of the most serious diseases of tomato (Solanum lycopersicum L.) throughout the world. There are three races of the pathogen (races 1, 2 and 3), and the deployment of three single, dominant resistance genes corresponding to each of these has been the primary means of controlling the disease. The I-3 gene was introgressed from S. pennellii and confers resistance to race 3. Although I-3 provides effective control, it is negatively associated with several horticultural traits, including increased sensitivity to bacterial spot disease (Xanthomonas spp.). To test the hypothesis that this association is due to linkage with unfavorable alleles rather than to pleiotropy, we used a map-based approach to develop a collection of recombinant inbred lines varying for portions of I-3 introgression. Progeny of recombinants were evaluated for bacterial spot severity in the field for three seasons, and disease severities were compared between I-3 introgression haplotypes for each recombinant. Results indicated that increased sensitivity to bacterial spot is not associated with the I-3 gene, but rather with an upstream region of the introgression. A survey of public and private inbred lines and hybrids indicates that the majority of modern I-3 germplasm contains a similarly sized introgression for which the negative association with bacterial spot likely persists. In light of this, it is expected that the development and utilization of a reduced I-3 introgression will significantly improve breeding efforts for resistance to Fusarium wilt race 3. PMID- 28986628 TI - [Wearables to support self-management of older adults with chronic diseases : A qualitative study from the perspectives of patients and physicians]. AB - BACKGROUND: The use of wearable devices (WD) is discussed as an option to support elderly chronically ill people. These technologies lack essential research regarding the improvement of self-management. This study aimes to identify perspectives, expectations and their underlying background of patients and physicians with respect to the usage of WDs to enhance self-management. METHODS: In this study a total of 14 patients and physicians were surveyed using a semi structured questionnaire design. The data were analyzed by qualitative content analysis. RESULTS: The participants have in general a positive attitude towards the use of WDs with respect to memory function, self-control, sense of security, documentation of vital parameters and communication about the disease, as well as suitability for everyday use; however, in many cases participants are concerned about the usage of WDs for a variety of reasons. They perceive the device as unnecessary or they lack technological self-confidence and felt controlled as well as data protection concerns. Participant responses show prerequisites which should be met for the usage of a WD requiring an individual needs assessment. CONCLUSION: The results show a potential of WDs to improve self-management. The usage of WD could have a positive effect on the course of the disease; however, personality and environmental factors should be taken into account to individually adjust and support the usage of WDs. Furthermore, the application of WDs should be integrated into a structured training program accompanied by healthcare professionals. For this purpose, funding and time-oriented framework conditions should be established. PMID- 28986629 TI - Incidental perifissural nodules on routine chest computed tomography: lung cancer or not? AB - OBJECTIVES: Perifissural nodules (PFNs) are a common finding on chest CT, and are thought to represent non-malignant lesions. However, data outside a lung cancer screening setting are currently lacking. METHODS: In a nested case-control design, out of a total cohort of 16,850 patients >= 40 years of age who underwent routine chest CT (2004-2012), 186 eligible subjects with incident lung cancer and 511 controls without were investigated. All non-calcified nodules >= 4 mm were semi-automatically annotated. Lung cancer location and subject characteristics were recorded. RESULTS: Cases (56 % male) had a median age of 64 years (IQR 59 70). Controls (60 % male) were slightly younger (p<0.01), median age of 61 years (IQR 51-70). A total of 262/1,278 (21 %) unique non-calcified nodules represented a PFN. None of these were traced to a lung malignancy over a median follow-up of around 4.5 years. PFNs were most often located in the lower lung zones (72 %, p<0.001). Median diameter was 4.6 mm (range: 4.0-8.1), volume 51 mm3 (range: 32 278). Some showed growth rates < 400 days. CONCLUSIONS: Our data show that incidental PFNs do not represent lung cancer in a routine care, heterogeneous population. This confirms prior screening-based results. KEY POINTS: * One-fifth of non-calcified nodules represented a perifissural nodule in our non-screening population. * PFNs fairly often show larger size, and can show interval growth. * When morphologically resembling a PFN, nodules are nearly certainly not a malignancy. * The assumed benign aetiology of PFNs seems valid outside the screening setting. PMID- 28986630 TI - Comparison of transient severe motion in gadoxetate disodium and gadopentetate dimeglumine-enhanced MRI: effect of modified breath-holding method. AB - OBJECTIVES: To compare the occurrence of transient severe motion (TSM) between gadoxetate disodium- and gadopentetate dimeglumine-enhanced MRI and between gadoxetate disodium-enhanced MRI scans obtained with and without the application of a modified breath-holding technique. METHODS: We reviewed 80 patients who underwent two magnetic resonance examinations (gadoxetate disodium-enhanced MRI and gadopentetate dimeglumine-enhanced MRI) with the application of a modified breath-holding technique (dual group). This group was compared with 100 patients who underwent gadoxetate disodium-enhanced MRI without the application of the modified breath-holding technique (single group). Patient risk factors and motion scores (1 [none] to 5 [non-diagnostic]) for each dynamic-phase imaging were analysed. RESULTS: In the dual group, mean motion scores did not differ significantly between gadoxetate disodium- and gadopentetate dimeglumine-enhanced MRI (p=0.096-0.807) in any phase. However, in all phases except the late dynamic phase, mean motion scores of the dual group were significantly lower than those in the single group. TSM incidence did not differ significantly between gadoxetate disodium- and gadopentetate dimeglumine-enhanced MRI in the dual group (3.8% vs. 1.3%, p=0.620). CONCLUSION: With proper application of the modified breath-holding technique, TSM occurrence with gadoxetate disodium-enhanced MRI was comparable to that associated with gadopentetate dimeglumine-enhanced MRI. KEY POINTS: * The modified breath-holding method significantly reduced the incidence of TSM. * Gadoxetate disodium and gadopentetate dimeglumine showed comparable motion scores. * TSM incidence was comparable between gadoxetate disodium- and gadopentetate dimeglumine-enhanced MRI. PMID- 28986631 TI - Comparative reliability and diagnostic performance of conventional 3T magnetic resonance imaging and 1.5T magnetic resonance arthrography for the evaluation of internal derangement of the hip. AB - OBJECTIVE: To compare the diagnostic accuracy of conventional 3T MRI against 1.5T MR arthrography (MRA) in patients with clinical femoroacetabular impingement (FAI). METHODS: Sixty-eight consecutive patients with clinical FAI underwent both 1.5T MRA and 3T MRI. Imaging was prospectively analysed by two musculoskeletal radiologists, blinded to patient outcomes and scored for internal derangement including labral and cartilage abnormality. Interobserver variation was assessed by kappa analysis. Thirty-nine patients subsequently underwent hip arthroscopy and surgical results and radiology findings were analysed. RESULTS: Both readers had higher sensitivities for detecting labral tears with 3T MRI compared to 1.5T MRA (not statistically significant p=0.07). For acetabular cartilage defect both readers had higher statistically significant sensitivities using 3T MRI compared to 1.5T MRA (p=0.02). Both readers had a slightly higher sensitivity for detecting delamination with 1.5T MRA compared to 3T MRI, but these differences were not statistically significant (p=0.66). Interobserver agreement was substantial to perfect agreement for all parameters except the identification of delamination (3T MRI showed moderate agreement and 1.5T MRA substantial agreement). CONCLUSION: Conventional 3T MRI may be at least equivalent to 1.5T MRA in detecting acetabular labrum and possibly superior to 1.5T MRA in detecting cartilage defects in patients with suspected FAI. KEY POINTS: * Conventional 3T MRI is equivalent to 1.5T MRA for diagnosing labral tears. * Conventional 3T MRI is superior to 1.5T MRA for diagnosing acetabular cartilage defect. * Conventional 3T MRI is equivalent to 1.5T MRA for diagnosing cartilage delamination. * Symptom severity score was significantly higher (p<0.05) in group proceeding to surgery. PMID- 28986632 TI - Phylogenetic analysis of standard metabolic rate of snakes: a new proposal for the understanding of interspecific variation in feeding behavior. AB - The current proposal about the variation of standard metabolic rates (SMR) in snakes predicts that SMR is influenced by the feeding frequency (frequent or infrequent feeders). However, feeding frequency in snakes is poorly studied and hard to quantify under natural conditions. Alternatively, foraging strategy was studied for a large number of species and is usually related to the feeding frequency. In this work, we performed a meta-analysis on the SMR of compiled data from 74 species of snakes obtained from the literature and five more different species of lanceheads (genus Bothrops), after categorization according to the foraging mode (ambush or active foraging) and regarding their phylogenetic history. We tested the hypothesis that foraging mode (FM) is a determinant factor on the interspecific variation of SMR despite the phylogenetic relationship among species. We demonstrated that FM predicted SMR, but there is also a partial phylogenetic structuration of SMR in snakes. We also detected that evolution rates of SMR in active foragers seem to be higher than ambush-hunting snakes. We suggested that foraging mode has a major effect over the evolution of SMR in snakes, which could represent an ecophysiological co-adaptation, since ambush hunters (with low feeding rates) present a lower maintenance energetic cost (SMR) when compared to active foragers. The higher SMR evolution rates for active foraging snakes could be related to a higher heterogeny in the degree of activity during hunting by active foragers when compared to ambush-hunting snakes. PMID- 28986633 TI - [The rheumatic cervical spine]. AB - BACKGROUND: The cervical spine is one of the main sites of manifestation in rheumatoid arthritis outside of the extremities. It can have a decisive influence on disease course via the occurrence of mechanical instabilities as well as neurologic symptoms. Both adequate diagnosis and the corresponding surgical treatment represent a challenge for the involved physicians. MATERIALS AND METHODS: This review presents relevant diagnostic strategies and possibilities for surgical intervention which aim to avoid potentially fatal neurologic symptoms. Basic literature and expert opinions are also discussed. RESULTS AND CONCLUSION: Through target-oriented surgical management, as well as tight clinical and radiologic monitoring during conservative and surgical therapy, potentially fatal disease courses can be avoided. PMID- 28986635 TI - [Aphakic Artisan/Verisyse IOLs as retropupillary implants : Video article]. AB - The retropupillary implantation of an iris claw intraocular lens (IOL) is an uncomplicated and fast technique for rehabilitation of aphakic eyes without any capsular structures and is presented in a video in the online version of this article. A complete anterior pars plana vitrectomy as shown in our case or an extensive preceding anterior vitrectomy as well as an intact iris are prerequisites. Special instruments for the implantation and fixation of the IOL are available to optimize the operative procedure. In addition to a rapid operating time the advantages of a trained surgeon are low complications rates and fast rehabilitation. For eyes with a defective iris diaphragm, ischemic vitreoretinopathy and uveitis, other implantation techniques should be selected. PMID- 28986634 TI - Contrast-enhanced MRI findings of the knee in healthy children; establishing normal values. AB - OBJECTIVES: To define normative standards for the knee in healthy children using contrast-enhanced MRI, focusing on normal synovial membrane thickness. Secondly, presence of joint fluid and bone marrow oedema was evaluated. METHODS: For this study, children without disorders potentially resulting in (accompanying) arthritis were included. Patients underwent clinical assessments, followed by contrast-enhanced MRI. MRI features were evaluated in consensus using the Juvenile Arthritis MRI Scoring (JAMRIS) system. Additionally, the presence of joint fluid was evaluated. No cartilage lesions or bone abnormalities were observed. RESULTS: We included 57 healthy children. The overall mean thickness of the normal synovial membrane was 0.4 mm (min-max; 0.0-1.8mm). The synovium was thickest around the cruciate ligaments and retropatellar and suprapatellar regions. The mean overall diameter of the largest pocket of joint fluid was 2.8 mm (min-max; 0.9-8.0mm). Bone marrow changes were observed in three children (all in the apex patellae). CONCLUSIONS: The normal synovial membrane was maximally 1.8 mm thick, indicating that the JAMRIS cut-off value of 2 mm can be considered a valid measure for evaluating synovial hypertrophy. Some joint fluid and bone marrow changes suggestive of bone marrow oedema in the apex patellae can be seen in healthy children. KEY POINTS: * Knowledge on the normal synovial appearance using contrast-enhanced MR is lacking. * In healthy children, normal synovial membrane is maximally 1.8 mm thick. * Normal synovium is thickest around the cruciate ligaments, retropatellar and suprapatellar. * Bone marrow oedema in the apex patellae is seen in healthy children. PMID- 28986636 TI - Optimising preoperative risk stratification tools for prostate cancer using mpMRI. AB - PURPOSE: To improve preoperative risk stratification for prostate cancer (PCa) by incorporating multiparametric MRI (mpMRI) features into risk stratification tools for PCa, CAPRA and D'Amico. METHODS: 807 consecutive patients operated on by robot-assisted radical prostatectomy at our institution during the period 2010 2015 were followed to identify biochemical recurrence (BCR). 591 patients were eligible for final analysis. We employed stepwise backward likelihood methodology and penalised Cox cross-validation to identify the most significant predictors of BCR including mpMRI features. mpMRI features were then integrated into image adjusted (IA) risk prediction models and the two risk prediction tools were then evaluated both with and without image adjustment using receiver operating characteristics, survival and decision curve analyses. RESULTS: 37 patients suffered BCR. Apparent diffusion coefficient (ADC) and radiological extraprostatic extension (rEPE) from mpMRI were both significant predictors of BCR. Both IA prediction models reallocated more than 20% of intermediate-risk patients to the low-risk group, reducing their estimated cumulative BCR risk from approximately 5% to 1.1%. Both IA models showed improved prognostic performance with a better separation of the survival curves. CONCLUSION: Integrating ADC and rEPE from mpMRI of the prostate into risk stratification tools improves preoperative risk estimation for BCR. KEY POINTS: * MRI-derived features, ADC and EPE, improve risk stratification of biochemical recurrence. * Using mpMRI to stratify prostate cancer patients improves the differentiation between risk groups. * Using preoperative mpMRI will help urologists in selecting the most appropriate treatment. PMID- 28986637 TI - Association of weight change with progression of meniscal intrasubstance degeneration over 48 months: Data from the Osteoarthritis Initiative. AB - OBJECTIVES: To investigate the association of weight change over 48 months with progression of meniscal intrasubstance degeneration (MID). METHODS: We studied 487 subjects with MID at baseline and after 48 months using 3-T MRI with the same protocol (FSE sequences with and without fat suppression). These participants lost weight (>=3%, n = 141), had moderate weight gain (3-10%, n = 77), substantial weight gain (>10%, n = 15) or maintained stable weight (n = 254). Progression of MID to a meniscal tear was assessed using the WORMS grading system and compared among weight change groups using logistic regression. ANOVA and chi square tests were used to study the differences in subjects' characteristics. RESULTS: Progression of MID increased from weight loss to substantial weight gain (p < 0.001) and was significantly more likely with both moderate weight gain (odds ratio [OR], 4.9; 95% confidence interval [CI] 2.4-8.9) and substantial weight gain (OR, 9.5; 95% CI 3.2-28.5) compared to stable weight. Results were similar in both menisci for moderate weight gain (medial: OR, 6.8; 95% CI 3.5 11.3; lateral: OR, 2.6; 95% CI 1.1-6.6) and substantial weight gain (medial: OR, 21.0; 95% CI 5.1-80.7; lateral: OR, 9.7; 95% CI 0.95-100.2). CONCLUSION: Weight gain is associated with an increased likelihood that meniscal intrasubstance degeneration will progress with the risk increasing with greater weight gain. KEY POINTS: * Subjects who gained weight were more likely to develop meniscal tears. * Greater amount of weight gain was associated with an increasing likelihood of progression. * Prevention of weight gain has health benefits for the meniscus. PMID- 28986638 TI - Expanding horizons in complement drug discovery: challenges and emerging strategies. AB - The complement system is best known for its role in innate immunity, providing a first line of defence against infection, maintaining tissue homeostasis by flagging apoptotic cells and debris for removal, and orchestrating crosstalk between adaptive and innate immunity. In a growing number of diseases, complement is known to drive pathogenesis or to contribute as an inflammatory amplifier of a disease trigger. Association of complement with common and devastating diseases has driven an upsurge in complement drug discovery, but despite a wealth of knowledge in the complexities of the cascade, and many decades of effort, very few drugs have progressed to late-stage clinical studies. The reasons for this are becoming clear with difficulties including high target concentration and turnover, lack of clarity around disease mechanism and unwanted side effects. Lessons learnt from drugs which are either approved, or are currently in late stage development, or have failed and dropped off the drug development landscape, have been invaluable to drive a new generation of innovative drugs which are progressing through clinical development. In this review, the challenges associated with complement drug discovery are discussed and the current drug development landscape is reviewed. The latest approaches to improve drug characteristics are explored and those agents which employ these technologies to improve accessibility to patients are highlighted. PMID- 28986639 TI - [Postoperative and posttherapeutic changes after primary bone tumors : What's important for radiologists?] AB - Posttreatment imaging of primary bone tumours represents a diagnostic challenge for radiologists. Depending on the primary bone tumour common radiological procedures, such as radiography, computed tomography (CT), and magnetic resonance imaging (MRI), are employed. Radiography and CT are particularly useful in benign bone tumours and in matrix-forming bone tumours. MRI comes into consideration with malignant tumour recurrence and tumoral soft tissue infiltration. Bone scintigraphy is of superior importance if a primarily multifocal manifestation of bone tumour or metastasizing tumour disease is suspected. Molecular imaging (FDG PET and hybrid imaging, using CT) are gaining increasing importance in light of monitoring neoadjuvant chemotherapy and detecting recurrent tumour appearance. The current literature shows sensitivity and specificity values for recurrent detection of up to 92% and 93%. Diagnostic accuracy is as high as 95%, thus, exceeding accuracy values for CT (67%) and MRI (86%) by far. Likewise, this is also applicable for the assessment of the neoadjuvant chemotherapy. Moreover, PET based modalities are able to establish prognostic statements using SUV-threshold values at baseline (especially for Ewing sarcomas). Advanced imaging techniques have made a great diagnostic step forward and have proven to be relevant and reproducible with respect to both relapse detection and treatment assessment. Furthermore, it is not clear whether a higher detection rate of early tumour recurrence will inevitably lead to better outcome and survival. PMID- 28986640 TI - Reduced GABA levels correlate with cognitive impairment in patients with relapsing-remitting multiple sclerosis. AB - OBJECTIVES: To investigate if brain gamma-aminobutyric acid (GABA) levels in patients with relapsing-remitting multiple sclerosis (RRMS) are abnormal compared with healthy controls, and their relationship to cognitive function in RRMS. METHODS: Twenty-eight RRMS patients and twenty-six healthy controls underwent magnetic resonance spectroscopy (MRS) at 3-T to detect GABA signals from posterior cingulate cortex (PCC), medial prefrontal cortex (mPFC) and left hippocampus using the 'MEGAPoint Resolved Spectroscopy Sequence' (MEGA-PRESS) technique. All subjects also underwent a cognitive assessment. RESULTS: In RRMS patients, GABA+ were lower in the PCC (p = 0.036) and left hippocampus (p = 0.039) compared with controls, decreased GABA+ in the PCC and left hippocampus were associated with specific cognitive functions (r = -0.452, p = 0.016 and r = 0.451, p = 0.016 respectively); GABA+ in the mPFC were not significantly decreased or related to any cognitive scores (p > 0.05). CONCLUSIONS: This study demonstrates that abnormalities of the GABAergic system may be present in the pathogenesis of RRMS and suggests a potential link between regional GABA levels and cognitive impairment in patients with RRMS. KEY POINTS: * GABA levels may decrease in patients with RRMS. * Lower GABA levels correlated with worse cognitive performance in patients with RRMS. * Dysfunctional GABAergic neurotransmission may have a role in cognitive impairment in RRMS. PMID- 28986641 TI - First detection of Rickettsia conorii ssp. caspia in Rhipicephalus sanguineus in Zambia. AB - Ticks are important vectors for Rickettsia spp. of the spotted fever group all around the world. Rickettsia conorii is the etiological agent of boutonneuse fever in the Mediterranean region and Africa. Tick identification was based on morphological features and further characterized using the 16S rRNA gene. The ticks were individually tested using pan-Rickettsia real-time-PCR for screening, and 23S-5S intergenic spacer region, 16S rDNA, gltA, sca4, ompB, and ompA genes were used to analyze the Rickettsia positive samples. Rickettsia conorii ssp. caspia was detected in tick collected in Zambia for the first time, thus demonstrating the possibility of the occurrence of human disease, namely Astrakhan fever, due to this Rickettsia ssp. in this region of Africa. The prevalence of R. conorii ssp. caspia was 0.06% (one positive tick out of 1465 tested ticks) and 0.07% (one positive tick out of 1254 tested Rh. sanguineus). PMID- 28986642 TI - Arbuscular common mycorrhizal networks mediate intra- and interspecific interactions of two prairie grasses. AB - Arbuscular mycorrhizal fungi form extensive common mycorrhizal networks (CMNs) that may interconnect neighboring root systems of the same or different plant species, thereby potentially influencing the distribution of limiting mineral nutrients among plants. We examined how CMNs affected intra- and interspecific interactions within and between populations of Andropogon gerardii, a highly mycorrhiza dependent, dominant prairie grass and Elymus canadensis, a moderately dependent, subordinate prairie species. We grew A. gerardii and E. canadensis alone and intermixed in microcosms, with individual root systems isolated, but either interconnected by CMNs or with CMNs severed weekly. CMNs, which provided access to a large soil volume, improved survival of both A. gerardii and E. canadensis, but intensified intraspecific competition for A. gerardii. When mixed with E. canadensis, A. gerardii overyielded aboveground biomass in the presence of intact CMNs but not when CMNs were severed, suggesting that A. gerardii with intact CMNs most benefitted from weaker interspecific than intraspecific interactions across CMNs. CMNs improved manganese uptake by both species, with the largest plants receiving the most manganese. Enhanced growth in consequence of improved mineral nutrition led to large E. canadensis in intact CMNs experiencing water-stress, as indicated by 13C isotope abundance. Our findings suggest that in prairie plant communities, CMNs may influence mineral nutrient distribution, water relations, within-species size hierarchies, and between species interactions. PMID- 28986644 TI - Traumatic occipito-cervical dissociation in adults: a Middle Eastern cohort study. AB - The objective of this study is to describe a series of cranio-cervical dissociation victims and evaluate their outcomes as well as discuss the clinical dilemmas we faced in the context of current literature evidence. This is a retrospective cohort study of traumatic occipito-cervical dissociation in five patients (three males and two females) encountered between 2010 and 2016 at a tertiary care facility in the Middle East region. All patients underwent occipito cervical fusion using screws and rods system with mean postoperative follow-up period of 2.5 years. All patients survived, and four were independently mobile and one wheel chair bound. Most had some degree of neurological sequelae, often due to associated injuries and all complained of limited neck range of motion. Contemporary literature review shows that CT scan with MRI is often the best diagnostic modality. Surgery is usually indicated though rare cases treated conservatively have been reported. The commonest predictor of mortality is missed injury, associated head injury and wide separation between the skull base and C1 on imaging studies. PMID- 28986643 TI - Risk factors and reasons for treatment abandonment among children with lymphoma in Malawi. AB - PURPOSE: Lymphoma is the commonest pediatric cancer in sub-Saharan Africa (SSA). Frequent treatment abandonment contributes to suboptimal outcomes. We examined risk factors and reasons for treatment abandonment for this population in Malawi. METHODS: We conducted a mixed methods study among children < 18 years old with newly diagnosed lymphoma, prospectively enrolled during 2013-2016. All children received standardized diagnosis and treatment, and were followed for up to 2 years. Treatment abandonment was defined as failure to attend prescribed chemotherapy within 4 weeks, or post-treatment visit within 3 months. Child, guardian, and household characteristics associated with treatment abandonment were assessed. Semi-structured interviews were conducted with primary caregivers of children experiencing treatment abandonment. RESULTS: Of 121 children with newly diagnosed lymphoma, 72 (60%) had complete information regarding child, guardian, and household characteristics. Of these, 56 (78%) had Burkitt's and 16 (22%) Hodgkin's lymphoma. Forty-nine (68%) were male, median age was 10.6 years (interquartile range [IQR] 7.9-13.0), and 26 (36%) experienced treatment abandonment. Lack of guardian education and travel time >= 4 h to clinic were independently associated with treatment abandonment, with adjusted hazard ratio (aHR) 3.8 [95% confidence interval (CI) 1.5-8.9, p = 0.005] and aHR 2.9 (95% CI 1.2-6.9, p = 0.019), respectively. Commonest reasons for treatment abandonment endorsed by 15 guardians were community influence, suboptimal clinic environment, logistical challenges, transport costs, treatment toxicities, loss of hope, alternative healers, and beliefs about cure. CONCLUSIONS: These findings highlight families at risk for treatment abandonment, underlying reasons, and opportunities to improve retention in care for pediatric cancer patients in SSA. PMID- 28986645 TI - Assessing the utility of a distress screening tool at capturing sexual concerns in a gyne-oncology follow-up clinic. AB - PURPOSE: Communication and assessment of sexual health within cancer care is poor despite high rates of sexual dysfunction in cancer survivors. Screening for distress programs have been implemented, as a standardized part of cancer care across Canada, with the aim of increasing identification and improving access to support. Alberta Health Services uses a general distress screening form, containing the Canadian Problem Checklist, which includes a list of possible problems, one of which is "intimacy/sexuality." Theoretically, the discreet nature of the screening for distress form may reduce patient discomfort in disclosing sexual concerns verbally, and therefore help health care providers identify patients requiring intervention. This study aims to determine the adequacy of this distress screening tool in identifying gynecological cancer patients who have an intimacy/sexuality concern. METHODS: A chart review was conducted on all follow-up visits in a gyne-oncology clinic over 1 year. Each patient's chart was reviewed to determine the prevalence of the distress screening form completion, prevalence of the "intimacy/sexuality" item being checked, and documentation of actions taken to address any reported intimacy/sexuality problems. RESULTS: Seven hundred thirty patient visits were recorded during this period with completed distress screening forms found on 79.0% (n = 577) of charts. Only 6% of the patients indicated an intimacy/sexuality concern on this form. Of those, only one third had documentation that their problem was addressed. CONCLUSIONS: These results call into question the utility of the intimacy/sexuality item on the Canadian Problem Checklist to identify gynecological cancer patients who have sexual concerns. Furthermore, even among those patients who indicated concerns, there is evidence that their problems are rarely addressed. Providers need to directly inquire with patients about their sexual health. PMID- 28986646 TI - Differentiation of benign and malignant solid pancreatic masses using magnetic resonance elastography with spin-echo echo planar imaging and three-dimensional inversion reconstruction: a prospective study. AB - OBJECTIVES: To determine the diagnostic performance of MR elastography (MRE) and compare it with serum CA19-9 in differentiating malignant from benign pancreatic masses, with emphasis on differentiating between pancreatic ductal adenocarcinoma (PDAC) and mass-forming pancreatitis (MFP). METHODS: We performed a prospective, consecutive, 24-month study in 85 patients with solid pancreatic masses confirmed by histopathologic examinations. The mass stiffness and stiffness ratio (calculated as the ratio of mass stiffness to the parenchymal stiffness) were assessed. The diagnostic accuracy was analysed by calculating the area under the ROC curve (AUROC). RESULTS: The final diagnosis included 54 malignant tumours (43 patients with PDAC) and 31 benign masses (24 patients with MFP). The stiffness ratio showed better diagnostic performance than the mass stiffness and serum CA19 9 for the differentiation between malignant and benign masses (AUC: 0.912 vs. 0.845 vs. 0.702; P = 0.026, P < 0.001) and, specifically, between PDAC and MFP (AUC: 0.955 vs. 0.882 vs. 0.745; P = 0.026, P = 0.003). The sensitivity, specificity, and accuracy of stiffness ratio for the differentiation of PDAC and MFP were all higher than 0.9. CONCLUSIONS: MRE presents an effective and quantitative strategy for non-invasive differentiation between PDAC and MFP based on their mechanical properties. KEY POINTS: * 3D MRE is useful for calculating stiffness of solid pancreatic tumours. * Stiffness ratio outperformed stiffness and CA19-9 for differentiating PDAC from MFP. * Incorporation of 3D MRE into a standard MRI protocol is recommended. PMID- 28986647 TI - Single- versus double-bundle suture button reconstruction of the forearm interosseous membrane for the chronic Essex-Lopresti lesion. AB - PURPOSE: Reconstruction of the ruptured interosseous membrane (IOM) is critical to restore forearm stability for the chronic Essex-Lopresti injury. Positive outcomes have been reported following IOM reconstruction with a single-bundle suture button (Mini-Tightrope) construct, although recent work suggests that double-bundle Mini-TightRope(r) IOM reconstruction is biomechanically superior. The purpose of this study was to determine whether double-bundle Mini TightRope(r) reconstruction of the forearm IOM results in superior clinical outcomes to the single-bundle technique. METHODS: Five patients with chronic Essex-Lopresti injuries treated with double-bundle Mini-TightRope(r) IOM reconstruction were matched to five patients treated with single-bundle Mini TightRope(r) reconstruction. Improvement in clinical examination measures and patient-reported outcomes was compared between the groups. RESULTS: Results were good to excellent in all 10 patients. At final follow-up, forearm rotation was significantly better in the single-bundle group, while maintenance of ulnar variance was better in the double-bundle group. No significant differences were noted between the two groups for any other numerical outcomes, and no complications occurred. CONCLUSION: These findings suggest that while IOM reconstruction with a double-bundle Mini-TightRope(r) construct results in greater resistance to proximal migration of the radius in the intermediate term, there is a modest concomitant loss of forearm rotation when compared to single bundle reconstruction. LEVEL OF EVIDENCE: Therapeutic Level IV. PMID- 28986649 TI - [Mesothelioma]. AB - Malignant mesotheliomas are rare and aggressive tumours arising from mesothelial cells of the pleura and peritoneum. Infrequent sites of origin are the pericardium and tunica vaginalis testis. More than 80% of mesotheliomas are localized in the pleura. Men are more frequently affected than women. The median age is >60 years. Asbestos exposure is the best known aetilogical risk factor and is reported in 54-90% of patients. In Germany, malignant mesotheliomas caused by occupational asbestos exposure are compensated as occupational disease since 1977. Several neoplastic and non-neoplastic lesions like metastasis, sarcomas, lymphomas or pleuritis with reactive mesothelial proliferation have to be distinguished from malignant mesotheliomas. Especially, the pathohistological differentiation between atypical reactive mesothelial proliferation from malignant mesothelioma is a diagnostic challenge. PMID- 28986648 TI - Acute Myocarditis with Infarct-like Presentation in a Pediatric Population: Role of Cardiovascular Magnetic Resonance. AB - Chest pain is a typical symptom of acute myocarditis in adolescents. It may be indistinguishable from myocardial ischemia so it is called "infarct-like pattern." Cardiovascular magnetic resonance has an important role as a non invasive diagnostic tool. The aim of our study is to provide a description of an acute myocarditis series with infarct-like pattern and to evaluate the cardiovascular magnetic resonance role in a pediatric population. We included all pediatric patients (0-16 years) admitted to our hospital (May 2007-May 2016) with clinical diagnosis of acute myocarditis and infarct-like presentation (chest pain, EKG alterations, and released cardiac biomarkers). Diagnosis was confirmed with cardiovascular magnetic resonance using Lake Louise criteria. Seven patients (five males, two females) with a median age of 14 years (12.5-15.2) were included. All patients showed ST-segment changes and released cardiac biomarkers. Three patients had left ventricular hypertrophy and two presented mild systolic left ventricular dysfunction. All patients had at least two positive Lake Louise criteria. Late gadolinium enhancement was positive in all of them. With a median follow-up of 23 months (8-47), all of them are alive, with no cardiac symptoms and normal ventricular function. Infarct-like pattern is a typical presentation of acute myocarditis in adolescents. CMR should be performed in this population and may be considered as a first-line diagnostic tool. Its high sensitivity in infarct-like acute myocarditis may allow us to avoid endomyocardial biopsy. Unlike what was described in adults, late gadolinium enhancement does not imply worse outcome in our series. PMID- 28986650 TI - Expression of stem cell factors in the adult sea cucumber digestive tube. AB - Homeostatic cell turnover has been extensively characterized in mammals. In their adult tissues, lost or aging differentiated cells are replenished by a self renewing cohort of stem cells. The stem cells have been particularly well studied in the intestine and are clearly identified by the expression of marker genes including Lgr5 and Bmi1. It is, however, unknown if the established principles of tissue renewal learned from mammals would be operating in non-mammalian systems. Here, we study homeostatic cell turnover in the sea cucumber digestive tube, the organ with high tissue plasticity even in adult animals. Both the luminal epithelium and mesothelium express orthologs of mammalian Lgr5 and Bmi1. However, unlike in mammals, there is no segregation of these positively labeled cells to specific regions in the luminal epithelium, where most of the cell proliferation would take place. In the mesothelium, the cells expressing the stem cell markers are tentatively identified as peritoneocytes. There are significant differences among the five anatomical gut regions in cell renewal dynamics and stem factor expression. The cloaca differs from the rest of the digestive tube as the region with the highest expression of the Lgr5 ortholog, lowest level of Bmi1 and the longest retention of BrdU-labeled cells. PMID- 28986651 TI - A study on the clinical characteristics of treating nevus of Ota by Q-switched Nd:YAG laser. AB - The purpose of this study was to retrospectively analyze the clinical characteristics of treating nevus of Ota by Q-switched Nd:YAG laser in Laser Cosmetology Center of Department of Dermatology, the Second Hospital, Xi'an Jiaotong University. The data of 1168 patients of nevus of Ota were analyzed retrospectively, which included the correlation among lesion color, treatment sessions, sex, age, lesion types, and effect. The Q-switched (QS) Nd:YAG laser system had a higher number of treatment sessions which were positively associated with a better response to treatment. Other variables, including gender, age, the categorization of the lesion according to Tanino's classification, and the color of the lesion, were not associated with the response to treatment. The treatment of nevus of Ota with QS Nd:YAG laser is safe and effective, with rare complications. PMID- 28986652 TI - Infant Development and Pre- and Post-partum Depression in Rural South African HIV Infected Women. AB - HIV-exposed infants born to depressed women may be at risk for adverse developmental outcomes. Half of HIV-infected women in rural South Africa (SA) may suffer from pregnancy-related depression. This pilot study examined the impact of depression in HIV-infected women in rural SA on infant development. Mother-infant dyads (N = 69) were recruited in rural SA. Demographics, HIV disclosure, depression, male involvement, and alcohol use at baseline (18.35 +/- 5.47 weeks gestation) were assessed. Male involvement, depression, infant HIV serostatus and development were assessed 12 months postnatally. Half of the women (age = 29 +/- 5) reported depression prenatally and one-third reported depression postnatally. In multivariable logistic regression, not cohabiting with their male partner, nondisclosure of HIV status, and postnatal depression predicted cognitive delay; decreased prenatal male involvement predicted delayed gross motor development (ps < 0.05). Assessing pregnancy-related depression among HIV-infected women and infant development and increasing male involvement may reduce negative developmental outcomes among HIV-exposed or infected infants. PMID- 28986653 TI - Pool size ratio of the substantia nigra in Parkinson's disease derived from two different quantitative magnetization transfer approaches. AB - PURPOSE: We sought to measure quantitative magnetization transfer (qMT) properties of the substantia nigra pars compacta (SNc) in patients with Parkinson's disease (PD) and healthy controls (HCs) using a full qMT analysis and determine whether a rapid single-point measurement yields equivalent results for pool size ratio (PSR). METHODS: Sixteen different MT-prepared MRI scans were obtained at 3 T from 16 PD patients and eight HCs, along with B1, B0, and relaxation time maps. Maps of PSR, free and macromolecular pool transverse relaxation times ([Formula: see text], [Formula: see text]) and rate of MT exchange between pools (k mf ) were generated using a full qMT model. PSR maps were also generated using a single-point qMT model requiring just two MT-prepared images. qMT parameter values of the SNc, red nucleus, cerebral crus, and gray matter were compared between groups and methods. RESULTS: PSR of the SNc was the only qMT parameter to differ significantly between groups (p < 0.05). PSR measured via single-point analysis was less variable than with the full MT model, provided slightly better differentiation of PD patients from HCs (area under curve 0.77 vs. 0.75) with sensitivity of 0.75 and specificity of 0.87, and was better than transverse relaxation time in distinguishing PD patients from HCs (area under curve 0.71, sensitivity 0.87, and specificity 0.50). CONCLUSION: The increased PSR observed in the SNc of PD patients may provide a novel biomarker of PD, possibly associated with an increased macromolecular content. Single-point PSR mapping with reduced variability and shorter scan times relative to the full qMT model appears clinically feasible. PMID- 28986654 TI - Soybean peroxidase immobilized on delta-FeOOH as new magnetically recyclable biocatalyst for removal of ferulic acid. AB - A significant enhancement in the catalytic performance due to enzymes immobilization is a great way to enhance the economics of biocatalytic processes. The soybean peroxidase (SP) immobilization under ferroxyte and the ferulic acid removal by the enzyme free and immobilized were investigated. The immobilization via silica-coated ferroxyte nanoparticles was effective, and immobilization yield of 39%. The scanning electron microscopy (SEM) images showed significant changes in the materials morphology. Substantial differences were observed in the particles' Fourier Transform Infrared (FTIR) spectra. The magnetic catalyst revealed a better performance than the free enzyme in the ferulic acid conversion, presenting a good V max/K m ratio when compared with the free enzyme. The reuse evaluated by ten cycles exhibited excellent recycling, remaining constant between the sixth and seventh cycles. The use of magnetic nanocatalyst becomes possible to eliminate the high operational costs, and complicated steps of the conventional enzymatic processes. Thus, a viable industrial route for the use of the enzyme as catalyst is possible. PMID- 28986655 TI - GILP family: a stress-responsive group of plant proteins containing a LITAF motif. AB - Lipopolysaccharide-induced tumor necrosis factor-alpha (LITAF) is a membrane protein that is highly dependent on correct location to exert transcription factor activity and protein quality control. In humans, LITAF, PIG7 (p53 inducible gene 7), and SIMPLE (small integral membrane protein of the lysosome/late endosome) refer to the same gene, which acts as a tumor suppressor. Several studies have shown that the transcription factor activity and nuclear translocation of LITAF protein are critical for the induction of several immune cells via classical pathways. In plants, LITAF protein corresponds to the plasma membrane protein AtGILP (Arabidopsis thaliana GSH-induced LITAF domain protein). The conservation of LITAF proteins across species and their putative role is still unclear. In this study, we investigate the LITAF-containing proteins, which we call GILP proteins, in Viridiplantae. We identified a total of 59 genes in 46 species, whose gene copies range from one to three. Phylogenetic analysis showed that multiple copies were originated via block duplication posteriorly to monocot and eudicot separation. Analysis of the LITAF domain of GILP proteins allowed the identification of a putative domain signature in Viridiplantae, containing a CXXCX41HXCPXC motif. The subcellular location for the majority of GILP proteins was predicted to be in the plasma membrane, based on a transmembrane domain positioned within the LITAF domain. In silico analysis showed that the GILP genes are neither tissue-specific nor ubiquitously expressed, being responsive to stress conditions. Finally, investigation of the GILP protein network resulted in the identification of genes whose families are known to be involved with biotic and/or abiotic stress responses. Together, the expression modulation of GILP genes associated with their plasma membrane location suggests that they could act in the signaling of biotic/abiotic stress response in plants. PMID- 28986656 TI - Sustainability of Statewide Rapid HIV Testing in Labor and Delivery. AB - The objective was to assess sustainability of a statewide program of HIV rapid testing (RT) for pregnant women presenting for delivery with unknown HIV status. This is a population-based retrospective cohort study of women delivered in Illinois hospitals (2012-15). Deidentified data on RT metrics from state-mandated surveillance reports were compared using descriptive statistics and non parametric tests of trend. Over 95% of the 608,408 women delivered had documented HIV status at presentation. The rate of undocumented HIV status rose from 4.19 to 4.75% (p < 0.001). However, overall 99.60% of women with undocumented status appropriately received RT and the proportion who did not receive RT declined (p = 0.003). The number of neonates discharged with unknown HIV status declined (p = 0.011). RT identified 23 new HIV diagnoses, representing 4.62% of maternal HIV diagnoses. In conclusion, statewide perinatal HIV RT resulted in nearly 100% of Illinois mother-infant dyads with known HIV status. Sustained RT completion represents an important prevention safety net. PMID- 28986657 TI - Influences of Different Halophyte Vegetation on Soil Microbial Community at Temperate Salt Marsh. AB - Salt marshes are transitional zone between terrestrial and aquatic ecosystems, occupied mainly by halophytic vegetation which provides numerous ecological services to coastal ecosystem. Halophyte-associated microbial community plays an important role in the adaptation of plants to adverse condition and also affected habitat characteristics. To explore the relationship between halophytes and soil microbial community, we studied the soil enzyme activities, soil microbial community structure, and functional gene abundance in halophytes- (Carex scabrifolia, Phragmites australis, and Suaeda japonica) covered and un-vegetated (mud flat) soils at Suncheon Bay, South Korea. Higher concentrations of total, Gram-positive, Gram-negative, total bacterial, and actinomycetes PLFAs (phospholipid fatty acids) were observed in the soil underneath the halophytes compared with mud flat soil and were highest in Carex soil. Halophyte-covered soils had different microbial community composition due to higher abundance of Gram-negative bacteria than mud flat soil. Similar to PLFA concentrations, the increased activities of beta-glucosidase, cellulase, phosphatase, and sulfatase enzymes were observed under halophyte soil compared to mud flat soil and Carex exhibited highest activities. The abundance of archaeal 16S rRNA, fungal ITS, and denitrifying genes (nirK, nirS, and nosZ) were not influenced by the halophytes. Abundance bacterial 16S rRNA and dissimilatory (bi)sulfite (dsrA) genes were highest in Carex-covered soil. The abundance of functional genes involved in methane cycle (mcrA and pmoA) was not affected by the halophytes. However, the ratios of mcrA/pmoA and mcrA/dsrA increased in halophyte-covered soils which indicate higher methanogenesis activities. The finding of the study also suggests that halophytes had increased the microbial and enzyme activities, and played a pivotal role in shaping microbial community structure. PMID- 28986658 TI - Multifocal metastatic chordoma to the soft tissues of the fingertips: a case report including sonographic features and a review of the literature. AB - Chordoma is a rare, locally aggressive tumor which commonly metastasizes, most often to the lung, liver, and spine. In this case report, a 59-year-old male with history of sacral chordoma and pulmonary metastases presented to the emergency department with swelling and discoloration of multiple left fingertips. The initial radiographs led to a presumptive diagnosis of gout, which did not respond to medical therapy. An ultrasound demonstrated multiple solid masses with vascular hyperechoic septations which were subsequently biopsied and proven to be metastatic chordoma. Metastatic disease to the hand is a well documented but rare manifestation of many malignancies. The clinical presentation and radiographic features of multifocal hand metastases may mimic entities such as systemic deposition and granulomatous diseases. To the best of our knowledge, this is the first case report of soft tissue chordoma metastases to the fingertips as well as the first reported sonographic description of chordoma metastases. PMID- 28986659 TI - HPV vaccination in Japan: results of a 3-year follow-up survey of obstetricians and gynecologists regarding their opinions toward the vaccine. AB - BACKGROUND: In Japan, the cervical cancer preventative HPV vaccination rate has dramatically declined, directly as a result of repeated broadcasts of so-called adverse events and the resulting suspension of the government's recommendation. Our previous survey of obstetricians and gynecologists in Japan regarding their opinions toward HPV vaccination revealed that these key specialists were as negatively influenced by the reports of purported negative events as were the general population. Here, we report a 3-year follow-up survey of these clinicians. METHODS: We reused the same questionnaire format as used in our 2014 survey, but added new questions concerning opinions regarding a WHO statement and reports of a Japanese nation-wide epidemiological study related to the adverse events, released in 2015 and 2016, respectively. RESULTS: The response rate was 46% (259/567): 5 (16.1%) of 31 doctors had inoculated their own teenaged daughters during the time period since the previous survey, despite the continued suspension of the governmental recommendation, whereas in the previous survey none of the doctors had done so. Among the respondents, the majority claimed awareness of the recent pro-vaccine WHO statement (66.5%), and of the report of a Japanese epidemiological study (71.5%), and a majority affirmed they currently held positive opinions of the safety (72.7%) and effectiveness (84.3%) of the HPV vaccine. CONCLUSIONS: Our re-survey of Japan's obstetricians and gynecologists regarding their opinions about the HPV vaccine found that their opinions have changed, potentially leading to a more positive future re-engagement for HPV vaccination in Japan. PMID- 28986660 TI - Risk Factors for Rescue Therapy in Crohn's Patients Maintained on Infliximab After Withdrawal of the Immunomodulator: A Long-Term Follow-Up. AB - BACKGROUND: Usefulness of thiopurine and scheduled infliximab combination therapy in non-immunomodulator (IM)-naive Crohn's disease (CD) patients and the optimal length of dual therapy are still debated. AIMS: To determine proportion of patients developing disease flare requiring rescue therapy and risk factors associated with disease flare after de-escalation of IM from combination therapy. METHODS: Adult CD patients in clinical remission on combination therapy were identified from a large single-center database between 2002 and 2009. Patients who had their IM stopped in the absence of adverse events were included. Association between clinical and demographic variables and time until rescue therapy was analyzed using Cox-proportional hazard models. RESULTS: Forty-three CD patients on combination therapy in clinical remission at time of IM de escalation were identified and followed up for a median duration of 61.6 months (range 5.4-129.5). Median duration of remission on combination therapy prior to IM de-escalation was 12.0 months (range 4-74). Thirty-one patients (72.1%) required rescue therapy during follow-up. On multivariable analysis, age at diagnosis < 16 years versus > 40 years (HR 4.55, 95% CI 1.18-17.62, p = 0.028), using methotrexate instead of azathioprine in combination with infliximab (HR 3.37, 95% CI 1.14, 9.96, p = 0.028), and duration of combination therapy < 6 months (HR 5.68, 95% CI 1.58, 20.36, p = 0.007) increased risk for rescue therapy. CONCLUSIONS: A large proportion of CD patients on combination therapy experienced a flare following IM withdrawal. Young age at diagnosis, short duration of combination therapy, and methotrexate use were independent predictors of the need for rescue therapy. PMID- 28986661 TI - [Aspergillus in airway material : Ignore or treat?] AB - Fungi of the genus Aspergillus are ubiquitously present. Even though humans inhale Aspergillus spores daily under natural conditions, Aspergillus-associated pulmonary diseases only occur under special circumstances. Whether an Aspergillus associated disease develops and which type of Aspergillus-associated disease develops depends on the constitution of the host. The spectrum of Aspergillus associated pulmonary diseases ranges from allergic diseases, such as hypersensitivity pneumonitis to allergic infectious diseases, such as allergic bronchopulmonary aspergillosis (ABPA) and bronchocentric granulomatosis (BG) to infectious diseases, such as invasive (IA) or semi-invasive aspergillosis (SIA) and chronic pulmonary aspergillosis (CPA). Identification of Aspergillus spp. from sputum or bronchopulmonary secretions is not sufficient for a definitive diagnosis of Aspergillus-associated infections. The gold standard is the identification of Aspergillus spp. from lung tissue by culture or by histopathological methods; however, in clinical practice the decision to initiate antifungal therapy is more often based on immunological methods, such as the detection of Aspergillus-specific IgG antibodies from peripheral blood or galactomannan antigens from bronchoalveolar lavages. Acute IA or SIA infections have a high mortality and require immediate antifungal therapy. With rare exceptions CPA cannot be cured by medicinal therapy alone; however, active CPA can be brought into remission with antifungal therapy. Eradication of Aspergillus in CPA can as a rule only be successful using a combined antimycotic and surgical intervention. PMID- 28986662 TI - Mesenchymal stem cells in peripheral blood of severely injured patients. AB - PURPOSE: Mesenchymal stem cells (MSCs) are primarily stromal cells present in bone marrow and other tissues that are crucial for tissue regeneration and can be mobilized into peripheral blood after different types of organ damage. However, little is known about MSC appearance in blood in the setting of polytrauma. METHODS: We conducted a monocentered and longitudinal observational clinical study in 11 polytraumatized patients with an injury severity score (ISS) >= 24 to determine the numbers of MSCs in peripheral blood. Blood was collected from healthy volunteers and patients after polytrauma in the emergency room and 4, 12, 24, 48 h, 5 and 10 day later, and cells carrying MSC-surface markers (negative for CD45, positive for CD29, CD73, CD90, CD105, and CD166 in different combinations also employing the more stringent markers STRO1 and MSCA1) were detected and characterized using flow cytometry. Relative numbers of MSC-like cells were correlated with clinical parameters to evaluate if specific injury patterns had an influence on their presence in the blood cell pool. RESULTS: We were able to detect MSC marker-positive cells in both cohorts; however, the percentage of those cells present in the blood of patients during the first 10 day after injury was mostly similar to healthy volunteers, and significantly lowers starting at 4 h post trauma for one marker combination when compared to controls. Furthermore, the presence of a pelvis fracture was partly correlated with reduced relative numbers of MSC-like cells detectable in blood. CONCLUSIONS: Polytrauma in humans was associated with partly reduced relative numbers of MSC like cells detected in peripheral blood in the time course after injury. Further studies need to define if this reduction was due to lower mobilization from the bone marrow or to active migration to the sites of injury. PMID- 28986663 TI - Dislocations after use of dual-mobility cups in cementless primary total hip arthroplasty: prospective multicentre series. AB - BACKGROUND: The purpose of this study was to investigate the incidence of dislocation and specific complications of the dual-mobility cup. METHODS: The arthroplasties involved 167 hips in 165 patients; 51 hips (30.5%) were in men and 116 (69.4%) were in women. The active articulation E1(r) dual-mobility cup (Biomet, Warsaw, IN, USA) was used, and the surgical approach was posterolateral in 120 hips and anterolateral in 47 hips. RESULTS: Four (2.3%) dislocations were observed. Mean time of dislocation was 30.5 days post-operatively. Three incomplete reductions occurred during closed reduction. When comparing parameters between dislocation and no-dislocation groups, there were no differences in patient and surgical parameters. However, all dislocations occurred in patients with femoral neck fractures and in the posterolateral approach group. CONCLUSION: The incidence of dislocation in total hip arthroplasty (THA) using a dual mobility cup was acceptable, and cup diameter of the dislocation group was substantially larger than that of no-dislocation group. Based on clinical outcomes of our study, we conclude that the dual-mobility cup is a reliable option in THA, and further studies are necessary. PMID- 28986664 TI - A 23-Nucleotide Deletion in STK11 Gene Causes Peutz-Jeghers Syndrome and Malignancy in a Chinese Patient Without a Positive Family History. AB - BACKGROUND AND AIMS: Peutz-Jeghers syndrome (PJS) is an autosomal-dominant genetic disease caused by mutations in the tumor suppressor gene, STK11, which is characterized by gastrointestinal hamartomas, melanin spots on the lips and the extremities, and an increased risk of developing both gastrointestinal and extraintestinal malignancies. METHODS AND RESULTS: We treated a PJS patient without a positive family history, who possessed typical clinical manifestations including polyp canceration. In order to explore the genotype of this patient, blood samples were collected from all the available family members. The whole coding region and the flanking regions of the STK11 gene were amplified by polymerase chain reaction and analyzed by Sanger sequencing. Molecular analysis of the STK11 gene here revealed a 23-nucleotide deletion (c.426 448delCGTGCCGGAGAAGCGTTTCCCAG) in exon 3, resulting in a change of 13 codons and a truncating protein (p.S142SfsX13). This mutation was not found in normal individuals in this family including her parents or in 100 control individuals. Protein structure prediction indicated a dramatic loss of the kinase domain and complete loss of the C-terminal regulatory domain. CONCLUSIONS: The results presented here enlarge the spectrum of STK11 mutation both disease-causing and malignancy-causing. PMID- 28986665 TI - Investigating cell functioning by theoretical analysis of cell-to-cell variability. AB - Here we discuss cell-to-cell variability in isogenic cell populations on the basis of an analogy between the processes of vesicle self-reproduction and cell self-replication. A short review of the theoretical analysis of vesicle self reproduction is presented to indicate that this process only occurs under the fulfillment of specific criteria: causal relations between the values of vesicle variables involved in its growth and division, and the parameters of the environment. It is shown that when division is asymmetric, both vesicle birth size and interdivision times are variable. We argue that during cell self replication, the balance between processes of cell growth and division also relies on causal relations between the corresponding cellular variables. A possible method is suggested to unravel previously unidentified causal relations between cell variables from the relationships between their variability parameters such as the widths of their probability distributions and their correlation coefficients. The method is outlined by reviewing the results of the corresponding analysis applied to a population of red blood cells. Some novel research directions are suggested that could lead from the analysis of cell-to cell variability to a better understanding of the organizational structure of cells and possibly also their evolutionary origin. PMID- 28986666 TI - Primary central nervous system malignant melanoma with leptomeningeal melanomatosis: a case report and review of the literature. AB - Leptomeningeal melanomatosis is an extremely rare variant of primary central nervous system (CNS) melanoma and has a poor prognosis and no standard treatment. Primary CNS melanoma is derived from the melanocytes of the leptomeninges. Here, we describe a case of a 37-year-old male who visited our hospital due to worsening headaches. Characteristic imaging findings of this tumor type include hyper-dense lesions that are enhanced by contrast medium on computed tomography and hyper-intensity on T1-weighted magnetic resonance images and iso- to hypo intensity on T2-weighted magnetic resonance images. Imaging of the CNS in our patient showed several lesions of this type. Pathological diagnosis and exclusion of systemic melanoma are required to confirm primary CNS malignant melanoma. Partial resection of the mass in the left temporal lobe of this patient was performed, and histological analysis showed pigmentation, melanin black-45 positivity, and BRAF mutation. Because no lesions were found outside the CNS following a thorough whole-body search, he was diagnosed with primary CNS malignant melanoma with leptomeningeal melanomatosis. He was treated with whole brain radiation and the BRAF kinase inhibitor vemurafenib. His condition worsened, and he was given the anti-programmed cell death-1 antibody nivolumab as second-line therapy. This was also unsuccessful, and he died 5 months after treatment initiation. Further studies are needed to improve treatment and prognosis of this rare but serious disease. PMID- 28986668 TI - [Development of teaching and training in geriatrics]. PMID- 28986669 TI - HIV Risk Behaviors and Utilization of Prevention Services, Urban and Rural Men Who Have Sex with Men in the United States: Results from a National Online Survey. AB - Rural men who have sex with men (MSM) are heavily affected by HIV, and many lack culturally competent HIV prevention resources. Rural MSM may find sexual partners on the internet, which may also be a way to deliver prevention services to them. To understand the differences between rural and urban MSM with respect to HIV risk factors and behaviors and the utilization of online HIV prevention services, we used data from the 2012 Web-Based HIV Behavioral Survey (WHBS). Using WHBS data collected between June and August 2012, we compared the characteristics of MSM with positive or unknown HIV infection status who had sex with a male in the past 12 months, from rural vs urban areas using Chi square tests and median tests. We used logistic regression and calculated adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) to compare self-reported HIV risk behaviors, HIV/STI testing behaviors, use of prevention services, and perceived discrimination. Of the 8166 MSM included in our analysis, 3583 (44%) were from rural areas, and 4583 (56%) were from urban areas. Compared to urban MSM, rural MSM were less likely to ever test for HIV (aPR = 0.94, CI 0.92-0.95), to be tested for HIV in the last year (aPR = 0.83, CI 0.79-0.87), or to receive free condoms (aPR = 0.83, CI 0.79-0.86) or individual prevention counseling in the past year (aPR = 0.86, CI 0.78-0.95). Rural MSM were less likely to have been tested in the last year for syphilis, gonorrhea, or chlamydia (aPR = 0.70, CI 0.62-0.78; aPR = 0.72, CI 0.64-0.81; aPR = 0.75, CI 0.67-0.85, respectively). Rural MSM also reported perceiving less tolerance of gays and bisexuals within their community (aPR = 0.80, CI 0.77-0.84). HIV prevalence is lower among MSM in rural areas compared to MSM in urban areas, but rural MSM report that they are more likely to face intolerance and are less likely to use basic HIV prevention services compared to urban MSM. Therefore, this hard-to-reach population could benefit from prevention services offered through the internet. PMID- 28986667 TI - Prolonged-Release Oxycodone/Naloxone Improves Anal Sphincter Relaxation Compared to Oxycodone Plus Macrogol 3350. AB - BACKGROUND: Opioid analgesics inhibit anal sphincter function and contribute to opioid-induced bowel dysfunction (OIBD). However, it is unknown whether the inhibition can be reduced by opioid antagonism with prolonged-release (PR) naloxone and how this compares to laxative treatment. AIMS: To compare the effects of combined PR oxycodone/naloxone or PR oxycodone plus macrogol 3350 on anal sphincter function and gastrointestinal symptoms. METHODS: A randomized, double-blind, crossover trial was conducted in 20 healthy men. Participants were treated for 5 days with combined PR oxycodone/naloxone or PR oxycodone plus macrogol 3350. Resting anal pressure, anal canal distensibility, and relaxation of the internal sphincter to rectal distension were evaluated before treatment (baseline) and on day 5. The Patient Assessment of Constipation Symptom (PAC-SYM) questionnaire, stool frequency, and stool consistency were assessed daily. RESULTS: Both PR oxycodone/naloxone and PR oxycodone plus macrogol treatment decreased sphincter relaxation compared to baseline (- 27.5%; P < 0.001 and - 14.7%; P = 0.01). However, sphincter relaxation was increased after PR naloxone/oxycodone treatment compared to macrogol (difference = + 17.6%; P < 0.001). Resting anal pressure and anal canal distensibility did not differ between treatments. PAC-SYM abdominal symptoms score was lower during PR naloxone compared to macrogol (0.2 vs. 3.2; P = 0.002). The number of bowel movements was lower during PR naloxone versus macrogol (4.2 vs. 5.4; P = 0.035). CONCLUSION: Relaxation of the internal anal sphincter was significantly better after PR oxycodone/naloxone treatment compared to PR oxycodone plus macrogol 3350. These findings highlight that OIBD may require specific therapy against the complex, pan-intestinal effects of opioids. PMID- 28986670 TI - Traumatic optic neuropathy treatment trial (TONTT): open label, phase 3, multicenter, semi-experimental trial. AB - PURPOSE: Intravenously administered erythropoietin (EPO) was firstly commenced (phase 1) in patients with indirect traumatic optic neuropathy (TON) by this group in 2011. It was re-tested by another group (phase 2) in 2014. This multicenter clinical trial was designed to compare its effect with intravenous steroid and observation. METHODS: Included were TON patients >=5 years of age and with trauma-treatment interval of <=3 weeks. Follow-up visits were set at 1, 2, 3, 7, 14, 30, and at least 90 days after treatment. EPO and methylprednisolone were infused intravenously every day for three consecutive days. Primary outcome measure was change in the best corrected visual acuity (BCVA). Secondary outcomes included change in color vision and relative afferent pupillary defect (RAPD), side effects, and factors affecting the final visual improvement. RESULTS: Out of 120 patients, 100 (EPO: 69, steroid: 15, observation: 16) were finally included. All three groups showed a significant improvement of BCVA which was not significantly different between the groups (adjusted for pretreatment BCVA). Color vision was significantly improved in the EPO group. Late treatment (>3 days) (odds ratio = 2.53) and initial BCVA of NLP (odds ratio = 5.74) significantly worsened visual recovery. No side effect was observed in any group. CONCLUSION: EPO, steroid, and observation showed a significant improvement of BCVA in patients with TON. Initial BCVA of NLP and late treatment (>3 days) were significant risk factors for visual improvement. PMID- 28986671 TI - Transcervical fat injection laryngoplasty for unilateral vocal fold paralysis: an easy way to do the job. AB - Unilateral vocal fold paralysis resulting in glottic incompetence can cause impairment of laryngeal functions, including airway protection and phonation. The objective of this study is to present an easy new technique for harvesting and injection of abdominal fat into the vocal fold for patients with unilateral vocal fold paralysis. This is a retrospective study of patients carried out on 16 patients suffering from unilateral vocal fold paralysis resulting from different etiologies. All patients were subjected to the protocol of voice assessment pre- and postoperatively. All patients were subjected to fat injection of the paralyzed vocal fold. There was a statistically significant difference between the pre- and postoperative grade of voice parameters. Vocal fold injection using fat medializes a paralyzed vocal fold by increasing vocal fold volume. Fat injections are safe and easily mastered; and in the absence of the standard settings for fat harvesting and injection, it could be performed with minimal equipment that are readily available in any operating room. PMID- 28986673 TI - From bird's eye views to molecular communities: two-layered visualization of structure-activity relationships in large compound data sets. AB - The analysis of structure-activity relationships (SARs) becomes rather challenging when large and heterogeneous compound data sets are studied. In such cases, many different compounds and their activities need to be compared, which quickly goes beyond the capacity of subjective assessments. For a comprehensive large-scale exploration of SARs, computational analysis and visualization methods are required. Herein, we introduce a two-layered SAR visualization scheme specifically designed for increasingly large compound data sets. The approach combines a new compound pair-based variant of generative topographic mapping (GTM), a machine learning approach for nonlinear mapping, with chemical space networks (CSNs). The GTM component provides a global view of the activity landscapes of large compound data sets, in which informative local SAR environments are identified, augmented by a numerical SAR scoring scheme. Prioritized local SAR regions are then projected into CSNs that resolve these regions at the level of individual compounds and their relationships. Analysis of CSNs makes it possible to distinguish between regions having different SAR characteristics and select compound subsets that are rich in SAR information. PMID- 28986672 TI - High accumulation in tobacco seeds of hemagglutinin antigen from avian (H5N1) influenza. AB - Tobacco seeds can be used as a cost effective system for production of recombinant vaccines. Avian influenza is an important respiratory pathogen that causes a high degree of mortality and becomes a serious threat for the poultry industry. A safe vaccine against avian flu produced at low cost could help to prevent future outbreaks. We have genetically engineered tobacco plants to express extracellular domain of hemagglutinin protein from H5N1 avian influenza virus as an inexpensive alternative for production purposes. Two regulatory sequences of seed storage protein genes from Phaseolus vulgaris L. were used to direct the expression, yielding 3.0 mg of the viral antigen per g of seeds. The production and stability of seed-produced recombinant HA protein was characterized by different molecular techniques. The aqueous extract of tobacco seed proteins was used for subcutaneous immunization of chickens, which developed antibodies that inhibited the agglutination of erythrocytes after the second application of the antigen. The feasibility of using tobacco seeds as a vaccine carrier is discussed. PMID- 28986674 TI - Surgical overreduction and hyperlordotic fusion of C1-C2 joint are associated with cervical sagittal malalignment. AB - INTRODUCTION: Previous studies have shown that hyperlordotic C1-C2 fusion was related to postoperative subaxial kyphosis. However, most of the patients in these studies were complicated with rheumatoid arthritis (RA). Moreover, no studies have specifically evaluated the relationship between C1-C2 fusion angle and cervical sagittal vertical axis (cSVA), T1 slope or cranial tilt (CRT) after posterior C1-C2 fusion. This study aimed to investigate the cervical sagittal alignment in non-RA patients following posterior C1-C2 fusion and the correlation between C1-C2 fusion angle and postoperative cervical sagittal alignment. MATERIALS AND METHODS: From August 2004 to December 2015, twenty-eight consecutive patients with an average age of 39.2 years (range 6-70 years) who underwent posterior C1-C2 fusion from a single institution were enrolled. The mean follow-up period was 30.7 months (range 12-77 months). Angles of Oc-C1, C1 C2, C2-C3 and C2-C7, cSVA, T1 slope and CRT were measured in lateral cervical radiographs in neutral position before surgery and at the final follow-up. RESULTS: C1-C2 angle significantly increased from 13.6 degrees +/- 12.4 degrees to 22.0 degrees +/- 8.1 degrees at the final follow-up (P < 0.001). A significant decrease was found both in Oc-C1 and C2-C7 angles from pre-operation to the final follow-up (P < 0.001 and P = 0.011, respectively). Moreover, cSVA and CRT dramatically increased from pre-operation to the final follow-up (P < 0.001). C1-C2 fusion angle was significantly associated with Oc-C1, C2-C7 angle, cSVA and CRT at the final follow-up. A significant correlation was also observed between postoperative change of C1-C2 angle and that of Oc-C1, C2-C7 angle, cSVA and CRT. CONCLUSIONS: Apart from decreased subaxial lordosis, posterior C1-C2 fusion in hyperextension may also lead to kyphotic change of atlanto-occipital alignment and increased tilting forward of the cervical spine. Therefore, intraoperative overreduction of C1-C2 angle and hyperlordotic C1-C2 fusion should be avoided to maintain the physiologic cervical sagittal alignment. PMID- 28986675 TI - Does the grading of chondromalacia patellae influence anterior knee pain following total knee arthroplasty without patellar resurfacing? AB - OBJECTIVES: The influence of chondromalacia patellae (CMP) on post-operative anterior knee pain (AKP) following total knee arthroplasty (TKA) remains controversial, and few studies have focused on the relationship between them. The purpose of this study was to determine whether different CMP grades affect the incidence of AKP after TKA without patellar resurfacing. METHODS: We performed a retrospective analysis of prospectively collected data on 290 TKAs with the use of the low contact stress mobile-bearing prosthesis, without patellar resurfacing in 290 patients from February 2009 to January 2013. Patients were assessed by the Outerbridge classification for CMP, visual analog scale for AKP, the Knee Society clinical scoring system of knee score (KS), function score (FS), the patellar score (PS) for clinical function, and patients' satisfaction. RESULTS: The intra operative grading of CMP: grade I in 30 patients, grade II in 68 patients, grade III in 97 patients, and grade IV in 95 patients. The incidence of AKP at 36-month follow-up was 10.3% (30/290). No statistical difference was detected among the different CMP grades in terms of the incidence of AKP (p = 0.995), patients' satisfaction (p = 0.832), KS (p = 0.228), FS (p = 0.713), and PS (p = 0.119) at 36-month follow-up. CONCLUSIONS: The findings may suggest no relevant influence of CMP grading on the incidence of AKP after TKA without patellar resurfacing. PMID- 28986677 TI - Split-bolus single scan CTA for evaluation of mesenteric ischemia. AB - PURPOSE: To evaluate split-bolus single scan CTA protocol for evaluation of acute mesenteric ischemia. MATERIALS AND METHODS: In this HIPAA-compliant IRB-approved study, consecutive patients evaluated for mesenteric ischemia between 11/2015 and 10/2016 were included. Patients scanned prior to 4/2016 were scanned with multiphasic CTA protocol and after with split-bolus single scan CTA. Objective and subjective evaluation was performed by three board-certified readers. Findings were correlated to composite clinical reference outcome. RESULTS: Eighty patients were included: 40 with split-bolus and 40 with multiphasic CTA protocol with similar age (60.3 +/- 16.2 years vs. 64.7 +/- 17.0 years, p = 0.19) and BMI (28.0 +/- 6.7 vs. 27.0 +/- 8.7, p = 0.56). SMA attenuation was higher in multiphasic protocol compared to split-bolus protocol (336.5 +/- 97.5 HU vs. 258.0 +/- 67.3 HU, p < 0.001) with similar SMV attenuation (multiphasic 213.7 +/- 58.4 HU vs. split-bolus 194.2 +/- 52.2 HU, p = 0.14). Optimal phase of bowel, liver, and spleen enhancement was seen in similar high proportion (94-99%) in both protocols. There were 8/40 (20%) positive cases of mesenteric ischemia in each group. There was no difference in the diagnostic confidence of the readers for evaluation of the mesenteric vessels and bowel ischemia. There were no missed cases of mesenteric ischemia in either group. Mean effective dose was 42% lower in the split-bolus group, p < 0.001. There was a higher number of axial images to review in multiphasic protocol compared to split-bolus protocol (437.9 +/- 48.7 vs. 263.5 +/- 31.2, p < 0.001). CONCLUSIONS: The split-bolus protocol for evaluation of mesenteric ischemia is clinically feasible with confident and accurate diagnostic ability, while reducing number of images and decreasing radiation exposure to the patient. PMID- 28986676 TI - Mechanisms of action of plant growth promoting bacteria. AB - The idea of eliminating the use of fertilizers which are sometimes environmentally unsafe is slowly becoming a reality because of the emergence of microorganisms that can serve the same purpose or even do better. Depletion of soil nutrients through leaching into the waterways and causing contamination are some of the negative effects of these chemical fertilizers that prompted the need for suitable alternatives. This brings us to the idea of using microbes that can be developed for use as biological fertilizers (biofertilizers). They are environmentally friendly as they are natural living organisms. They increase crop yield and production and, in addition, in developing countries, they are less expensive compared to chemical fertilizers. These biofertilizers are typically called plant growth-promoting bacteria (PGPB). In addition to PGPB, some fungi have also been demonstrated to promote plant growth. Apart from improving crop yields, some biofertilizers also control various plant pathogens. The objective of worldwide sustainable agriculture is much more likely to be achieved through the widespread use of biofertilizers rather than chemically synthesized fertilizers. However, to realize this objective it is essential that the many mechanisms employed by PGPB first be thoroughly understood thereby allowing workers to fully harness the potentials of these microbes. The present state of our knowledge regarding the fundamental mechanisms employed by PGPB is discussed herein. PMID- 28986678 TI - Fluid distribution in ankle and midfoot joints: MR findings in asymptomatic volunteers. AB - PURPOSE: The purpose of this study is to assess the amount of fluid in the joints of the ankle and midfoot on MR imaging in asymptomatic volunteers. MATERIALS AND METHODS: Twenty-one healthy asymptomatic volunteers (42 ankles) were evaluated with MRI imaging. There were 13 men and 8 women. The mean age was 24.7 years (19 42 years). MR imaging was performed on a 3T MR system using proton density weighted images with fat saturation (TR 2969, TE 30 ms, NA 2, slice thickness 2.5 mm). Images were obtained in three orthogonal planes. The images were interpreted by two radiologists in two sessions. The maximum size of the joint effusion was measured in one plane. Descriptive statistics and variation between interpretation sessions were calculated. RESULTS: Fluid in the anterior tibiotalar joint had a mean size of 2.0 mm (0.0-5.5 mm), in the posterior tibiotalar joint 3.1 mm (0.0-6.3 mm), in the talonavicular joint 0.7 mm (0.0-2.9 mm), and in the anterolateral recess 2.0 mm (0.0-4.3 mm). Fluid in the posterior aspect of the posterior subtalar joint had a mean size of 2.6 mm (0.0-9.4 mm), in the anterior aspect of the posterior subtalar joint 1.9 mm (0.0-6.6 mm), at the middle subtalar joint 0.1 mm (0.0-1.7 mm), and at the anterior subtalar joint 1.6 mm (0.0-6.0 mm). Fluid in the tibiofibular joint had a mean height of 8.1 mm (0.0 16.4 mm). CONCLUSION: In asymptomatic volunteers, moderate to large amounts of fluid were common in all joint recesses of ankle and midfoot, and most pronounced in the anterior and posterior tibiotalar joint, anterolateral recess, and posterior subtalar joint. This should not be mistaken for evidence of a pathological condition. PMID- 28986679 TI - A novel alphapartitivirus detected in Japanese pear. AB - Pyrus pyrifolia cryptic virus (PpCV) had been previously reported from Japanese pear (Pyrus pyrifolia). In analyses of Japanese pear, two other double-stranded (ds) RNA molecules (dsRNA4 and 5) were observed along with the three dsRNA segments from PpCV on an electrophoretic profile of isolated dsRNA. When the purified dsRNA sample was deep sequenced by a next-generation sequencer, two de novo assembled contigs corresponding to dsRNA4 and 5, with predicted amino acid sequences showing homologies to the RNA-dependent RNA polymerase and the capsid protein of Rose partitivirus, respectively, were found by BLAST analysis. The relationships between the two contigs and dsRNA4, 5 were confirmed by northern blot analyses with probes amplified using primers designed from the contigs. Terminal sequence analyses by rapid amplification of cDNA ends revealed that dsRNA4 and 5 were 1945 and 1788 bp long, respectively. The 5' terminal sequences (GUCAAAUU) of dsRNA4 and 5 were conserved. Based on genome size and phylogenetic analyses, the newly found virus is thought to be a member of the genus Alphapartitivirus. Thus, it has been designated as Pyrus pyrifolia partitivirus 2. PMID- 28986680 TI - Bayesian optimization for genomic selection: a method for discovering the best genotype among a large number of candidates. AB - KEY MESSAGE: A new pre-breeding strategy based on an optimization algorithm is proposed and evaluated via simulations. This strategy can find superior genotypes with less phenotyping effort. Genomic prediction is a promising approach to search for superior genotypes among a large number of accessions in germplasm collections preserved in gene banks. When some accessions are phenotyped and genotyped, a prediction model can be built, and the genotypic values of the remaining accessions can be predicted from their marker genotypes. In this study, we focused on the application of genomic prediction to pre-breeding, and propose a novel strategy that would reduce the cost of phenotyping needed to discover better accessions. We regarded the exploration of superior genotypes with genomic prediction as an optimization problem, and introduced Bayesian optimization to solve it. Bayesian optimization, that samples unobserved inputs according to the expected improvement (EI) as a selection criterion, seemed to be beneficial in pre-breeding. The EI depends on the predicted distribution of genotypic values, whereas usual selection depends only on the point estimate. We simulated a search for the best genotype among candidate genotypes and showed that the EI-based strategy required fewer genotypes to identify the best genotype than the usual and random selection strategy. Therefore, Bayesian optimization can be useful for applying genomic prediction to pre-breeding and would reduce the number of phenotyped accessions needed to find the best accession among a large number of candidates. PMID- 28986681 TI - The construction and application of a cell line resistant to novel subgroup avian leukosis virus (ALV-K) infection. AB - A novel avian leukosis viruses (ALV) subgroup named ALV-K was recently isolated from Chinese indigenous chickens which is different from the subgroups (A to E and J) that have previously been reported to infect chickens. More and more ALV-K strains have recently been isolated from local breeds of Chinese chickens. However, there are no more effective diagnostic methods for ALV-K other than virus isolation followed by envelope gene sequencing and comparison. Viral infection can be blocked through expression of the viral receptor-binding protein. In this study, we have engineered a cell line, DF-1/K, that expresses ALV-K env protein and thereby confers resistance to ALV-K infection. DF-1/K can be used in combination with the ALV-K susceptible cell line DF-1 as a specific diagnostic tool for ALV-K and provides a good tool for further research into the molecular mechanisms of interaction between ALV-K env protein and the host cell receptor. PMID- 28986682 TI - Efficacy and Safety of Pleurodesis Using Platelet-Rich Plasma and Fibrin Glue in Management of Postoperative Chylothorax After Esophagectomy. AB - INTRODUCTION: Chylothorax is by definition a collection of lymphatic fluids in the pleural cavity because of leakage from main thoracic duct or its tributaries. It is an uncommon but serious postoperative complication in esophageal cancer patients. There is no standard therapeutic algorithm for chylothorax because no prospective or randomized trials have yet been performed to evaluate the available treatment options. The aim of this study was to evaluate the efficacy of pleurodesis with a combination of platelet-rich plasma (PRP) and fibrin glue to the treatment of chylothorax after trans-hiatal esophagectomy. MATERIALS AND METHODS: We randomly allocated 52 consecutive esophageal cancer patients with postoperative chylothorax who did not respond to conservative management to either PRP fibrin glue pleurodesis or surgical thoracic duct ligation. 26 patients in each group were treated with PRP fibrin glue pleurodesis or surgical thoracic duct ligation in order to control chylothorax. Perioperative data, including success rate and complications of both interventions, were analyzed. RESULTS: Two groups were similar in terms of patients' demographics and tumor characteristics. All 26 patients in pleurodesis group (100%) and 20 patients in surgery group (76.9%) were successfully treated (p = 0.009). Seven patients (26.92%) in pleurodesis group required a second application of PRP fibrin glue after a week. The mean length of hospital stay was 53.50 +/- 16.662 days in surgery group and 36.04 +/- 8.224 days in pleurodesis group (p < 0.001). Although mortality rate in surgery group was higher than pleurodesis group, it was not statistically significant (p = 0.1621). There was no significant difference in complications between two groups either. No serious side effect occurred with PRP fibrin glue application. CONCLUSION: In conclusion, pleurodesis using PRP and fibrin glue for chylothorax after trans-hiatal esophagectomy was associated with significantly increased success rate, decreased ICU stay, decreased overall hospital stay, and decreased mortality compared with surgical thoracic duct ligation. No patient after PRFG required additional intervention including surgery. Thus, given the improved outcomes with PRFG pleurodesis, this technique may be considered in all patients with postoperative chylothorax after or during conservative management and before proceeding to more invasive interventions. PMID- 28986684 TI - Reverse shoulder arthroplasty in obese patients: analysis of functionality in the medium-term. AB - INTRODUCTION: Obesity is an epidemic nowadays and this fact conditions results in orthopaedic surgery. Very few studies evaluates if obesity is a risk factor for reverse shoulder arthroplasty. The aim of this study is to confirm if there are differences with regard to the outcomes in patients undergoing reverse shoulder arthroplasty according to their body mass index (BMI). MATERIALS AND METHODS: A total of 35 patients were enrolled in the study. Then divided into subpopulations according to their BMI and analyzed twice. First analysis set a division 30 of BMI and second set it in 35. ASES score, major complications, length of the hospital stay, radiolucent lines in components as well as scapular notching were assessed. RESULTS: No major complications were described in our patients. No differences were found related to hospital stay, radiolucent lines or scapular notching. However, in the second analysis (BMI < 35 and >= 35) statistical differences were found regarding ASES score. Poorer functional outcomes were described in the type-II obese and morbidly obese population. CONCLUSION: Functional outcomes of reverse shoulder arthroplasty are worse in patients with a BMI over 35. PMID- 28986683 TI - Hydroxyapatite-chitosan biocomposites synthesized in the simulated body fluid and their drug loading studies. AB - Hydroxyapatite (HAp) is a bioceramic applied in the biomedical areas, such as matrices for drug release control. Chitosan (CTS), a natural polymer, is another material has been widely investigated for its potential use in the drug delivery systems. In this study, the composites of HAp-CTS are produced in order to investigate their drug loading and release studies. First of all, HAp-CTS composites are produced in the presence of simulated body fluid (SBF). Analysis confirmed the structure of HAp-CTS composites. Secondly, composites are encapsulated with 5-Fluorouracil (5-FU). The weight ratio of CTS is varied to realize its effect on drug loading of 5-Fluorouracil, a cancer drug, for the ratios of 1:1, 1:2 and 1:4 of HAp-CTS. The weight ratio giving the greatest drug load efficiency is selected for the last step of the study. Crosslinking agent, glutaraldehyde, are changed from 0 to 5% on the selected sample, then, drug loading is examined again in various environment owing different pH. Furthermore, drug release studies are conducted. To understand the structure and morphology of the samples, XRD, FTIR, SEM and Uv-Spectrum are applied. It is observed that weight ratio of polymer and crosslinking agent can be manipulated to adjust drug loading. Release kinetics are shown the Fickian diffusion. This new produced material can be applicable for drug delivery. PMID- 28986685 TI - Contribution of market value chain to the control of African swine fever in Zambia. AB - African swine fever (ASF) is a worldwide disease of pigs endemic in most sub Saharan African countries. Zambia has been experiencing outbreaks of ASF for many years because the disease is endemic in the eastern part of the country, with incursion into the central part of Lusaka Province. The latest outbreaks of ASF in Lusaka occurred in 2013 with substantial pig mortalities, loss in trade, and cost of control measures and compensation of affected farmers. The aims of the study were to identify market value chain-related factors that were associated with ASF outbreaks and assess why these outbreaks are becoming frequent despite control measures being put in place. Using a mixed-method design, participants involved in the value chain were purposively sampled. Some pig farmers were included using a respondent-driven technique. Farmers came from Lusaka, Chilanga, Kafue, and Chongwe districts. Other participants included district veterinary officers, veterinary assistants, police officers, and veterinary staff manning veterinary checkpoints, abattoir and processing plant managers, meat inspectors, market chairpersons, and traders. Semi-structured questionnaires, in-depth interviews, and direct observations were used to collect data to come up with narrations, tables, and flow charts. In assessing the contribution of the value chain in ASF, aspects of ASF screening, market availability and procedures, knowledge on ASF transmission, occurrence of ASF outbreak, and regulation of pig movement were investigated. Despite government ASF control measures being applied, the following were noted: (1) low awareness levels of ASF transmission among pig farmers and traders; (2) only 50% of farmers had their animals screened for ASF before sale; (3) all the markets did not have the pork inspected; (4) laxity in enforcing livestock movement control because of inadequate police and veterinary staff manning checkpoints; (5) lack of enforcement of meat inspection and food safety regulations at pig markets; and (6) inadequate and bureaucratic ASF screening. Improving biosecurity; sensitizing farmers, traders, and all stakeholders in the pig value chain on ASF prevention and control; reinforcement of staff at checkpoints; and regulation of pig markets are some of the ways in which future outbreaks can be prevented. PMID- 28986686 TI - Diclofenac sodium gel therapy as an alternative to actinic cheilitis. AB - OBJECTIVE: Actinic cheilitis (AC) is a potentially malignant lesion caused by prolonged exposure to ultraviolet light. The aim of this research was to analyze the efficacy of diclofenac sodium 3% gel in the treatment of this condition, through clinical follow-up. METHODS: Thirty-one patients diagnosed with AC were instructed to perform a topical application of the gel three times a day for a period of 90 days. In each visit, a digital photography was obtained for verified progress and response to treatment. Two researchers evaluated all images after treatment was completed and assigned the following scores regarding clinical aspect of the lip: 1, complete improvement; 2, partial improvement; 3, no changes; 4, worsening of the clinical condition. In addition, the patients' tolerability to the drug and their satisfaction after treatment were evaluated. RESULTS: Twelve cases abandoned the treatment for reasons unrelated to the study. Ten participants showed total remission of all clinical features of the lesion and three had partial improvement of the characteristics. One participant presented worsening of clinical condition, and in five cases, treatment was discontinued due to development of mild adverse effects at the site of gel application. Regarding satisfaction analyses and tolerability to the drug, from 14 patients who completed treatment without adverse effects or complications, most agreed fully that they were satisfied with the therapy (n = 11) and that the drug was not irritating to the mouth (n = 9). Patients are being monitored without clinical signs of recurrence and/or progression of the lesions. CONCLUSION: Topical application of the drug has provided a convenient and well tolerated in most cases. CLINICAL RELEVANCE: Diclofenac sodium gel (3%) may be a promising alternative for treatment of actinic cheilitis. PMID- 28986687 TI - Surfactant chain length and concentration influence on the interfacial tension of two immiscible model liquids: a coarse-grained approach. AB - The interfacial tension between immiscible liquids is studied as a function of a model linear surfactant length and concentration using coarse-grained, dissipative particle dynamics numerical simulations. The adsorption isotherms obtained from the simulations are found to be in agreement with Langmuir's model. The reduction of the interfacial tension with increasing surfactant concentration is found to display some common characteristics for all the values of chain length modeled, with our predictions being in agreement with Szyszkowski's equation. Lastly, the critical micelle concentration is predicted for all surfactant lengths, finding exponentially decaying behavior, in agreement with Kleven's model. It is argued that these findings can be helpful guiding tools in the interpretation of available experiments and in the design of new ones with new surfactants and polymers. PMID- 28986688 TI - Unconventional Myosin ID is Involved in Remyelination After Cuprizone-Induced Demyelination. AB - Myelin, which is a multilamellar structure that sheathes the axon, is essential for normal neuronal function. In the central nervous system (CNS), myelin is produced by oligodendrocytes (OLs), which wrap their plasma membrane around axons. The dynamic membrane trafficking system, which relies on motor proteins, is required for myelin formation and maintenance. Previously, we reported that myosin ID (Myo1d) is distributed in rat CNS myelin and is especially enriched in the outer and inner cytoplasm-containing loops. Further, small interfering RNA (siRNA) treatment highlighted the involvement of Myo1d in the formation and maintenance of myelin in cultured OLs. Myo1d is one of the unconventional myosins, which may contribute to membrane dynamics, either in the wrapping process or transport of myelin membrane proteins during myelination. However, the function of Myo1d in myelin formation in vivo remains unclear. In the current study, to clarify the function of Myo1d in vivo, we surgically injected siRNA in the corpus callosum of a cuprizone-treated demyelination mouse model via stereotaxy. Knockdown of Myo1d expression in vivo decreased the intensities of myelin basic protein and myelin proteolipid protein immunofluorescence staining. However, neural/glial antigen 2-positive signals and adenomatous polyposis coli (APC/CC1)-positive cell numbers were unchanged by siRNA treatment. Furthermore, Myo1d knockdown treatment increased pro-inflammatory microglia and astrocytes during remyelination. In contrast, anti-inflammatory microglia were decreased. The percentage of caspase 3-positive cells in total CC1-positive OLs were also increased by Myo1d knockdown. These results indicated that Myo1d plays an important role during the regeneration process after demyelination. PMID- 28986689 TI - Microbial Resistance Mechanisms to the Antibiotic and Phytotoxin Fusaric Acid. AB - Fusaric acid (FA) produced by Fusarium oxysporum plays an important role in disease development in plants, including cotton. This non-specific toxin also has antibiotic effects on microorganisms. Thus, one expects a potential pool of diverse detoxification mechanisms of FA in nature. Bacteria and fungi from soils infested with Fusarium and from laboratory sources were evaluated for their ability to grow in the presence of FA and to alter the structure of FA into less toxic compounds. None of the bacterial strains were able to chemically modify FA. Highly FA-resistant strains were found only in Gram-negative bacteria, mainly in the genus of Pseudomonas. The FA resistance of the Gram-negative bacteria was positively correlated with the number of predicted genes for FA efflux pumps present in the genome. Phylogenetic analysis of predicted FA resistance proteins (FUSC, an inner membrane transporter component of the efflux pump) revealed that FUSC proteins having high sequence identities with the functionally characterized FA resistance protein FusC or Fdt might be the major contributors of FA resistance. In contrast, most fungi converted FA to less toxic compounds regardless of the level of FA resistance they exhibited. Five derivatives were detected, and the detoxification of FA involved either oxidative reactions on the butyl side chain or reductive reactions on the carboxylic acid group. The production of these metabolites from widely different phyla indicates that resistance to FA by altering its structure is highly conserved. A few FA resistant saprophytic or biocontrol strains of fungi were incapable of altering FA, indicating a possible involvement of efflux transporters. Deployment of both efflux and derivatization mechanisms may be a common feature of fungal FA resistance. PMID- 28986690 TI - The role of shear stress on cutaneous microvascular endothelial function in humans. AB - PURPOSE: Previous studies suggest that exercise and heat stress improve cutaneous endothelial function, caused by increases in shear stress. However, as vasodilatation in the skin is primarily a thermogenic phenomenon, we investigated if shear stress alone without increases in skin temperature that occur with exercise and heat stress increases endothelial function. We examined the hypothesis that repeated bouts of brief occlusion would improve cutaneous endothelial function via shear stress-dependent mechanisms. METHODS: Eleven males underwent a shear stress intervention (forearm occlusion 5 s rest 10 s) for 30 min, five times.week-1 for 6 weeks on one arm, the other was an untreated control. Skin blood flow was measured using laser-Doppler flowmetry, and endothelial function was assessed with and without NOS-inhibition with L-NAME in response to three levels of local heating (39, 42, and 44 degrees C), ACh administration, and reactive hyperaemia. Data are cutaneous vascular conductance (CVC, laser-Doppler/blood pressure). RESULTS: There were no changes in the control arm (all d <= 0.2, p > 0.05). In the experimental arm, CVC to 39 degrees C was increased after 3 and 6 weeks (d = 0.6; p <= 0.01). Nitric oxide contribution was increased after 6 weeks compared to baseline (d = 0.85, p < 0.001). Following skin heating to 42 degrees C and 44 degrees C, CVC was not different at weeks 3 or 6 (d <= 0.8, p > 0.05). For both 42 and 44 degrees C, nitric oxide contribution was increased after weeks 3 and 6 (d >= 0.4, p < 0.03). Peak and area-under-the-curve responses to ACh increased following 6 weeks (p < 0.001). CONCLUSIONS: Episodic increases in shear stress, without changes in skin or core temperature, elicit an increase in cutaneous microvascular reactivity and endothelial function. PMID- 28986691 TI - Spinal motion preservation surgery: indications and applications. AB - Fusion is one of the most commonly performed spinal procedures, indicated for a wide range of spinal problems. Elimination of motion though results in accelerated degeneration of the adjacent level, known as adjacent level disease. Motion preservation surgical methods were developed in order to overcome this complication. These methods include total disc replacement, laminoplasty, interspinous implants and dynamic posterior stabilization systems. The initial enthusiasm about these methods was followed by certain concerns about their clinical usefulness and their results. The main indications for total disc replacement are degenerative disc disease, but the numerous contraindications for this method make it difficult to find the right candidate. Application of interspinous implants has shown good results in patients with spinal stenosis, but a more precise definition is needed regarding the severity of spinal stenosis up to which these implants can be used. Laminoplasty has several advantages and less complications compared to fusion and laminectomy in patients with cervical myelopathy/radiculopathy. Dynamic posterior stabilization could replace conventional fusion in certain cases, but also in this case the results are successful only in mild to moderate cases. PMID- 28986692 TI - Short implants versus bone grafting and standard-length implants placement: a systematic review. AB - OBJECTIVES: The aim of this study was to conduct a systematic review to compare the survival rates between short implants (length < 10 mm) versus standard-length implants (>= 10 mm) inserted in grafted bone. As secondary outcomes, marginal bone loss and survival rates of the implant supported prostheses were also analysed. MATERIALS AND METHODS: Randomised controlled trials (RCT) that compared both techniques were searched on three electronic databases till June 2016, a manual search was performed on the bibliography of the collected articles, and the authors were contacted for additional references. The estimates of the interventions were expressed in relative risk (RR), mean implant survival rates and mean differences in marginal bone. RESULTS: Eight RCTs were included in this study. From a total of 458 short implants, 15 failed (mean survival rates = 96.7%), While from 488 regular implants, 13 failed (mean survival rates = 97.3%). The technique did not significantly affect: the implant failure rate (P > 0.05), with RR of 1.34 (95% CI 0.67-2.87), the mean differences of marginal bone loss (P = 0.18; MD - 0.04 mm [- 0.10; 0.02] 95% CI), at loading or prosthesis failures rates (RR:0.98; 95% CI 0.40-2.41). The mean differences of marginal bone at 1 year follow-up (post loading) presented significant marginal changes in the short implant group (P = 0.002; MD - 0.10 mm [- 0.16; - 0.03] 95% CI) although a significant high heterogeneity was found between groups. CONCLUSIONS: This systematic review suggests no difference between both techniques in the treatment of atrophic arches. However, more long-term RCTs are needed to evaluate the predictability at the long run. CLINICAL RELEVANCE: The use of short implants might be considered an alternative treatment, since it usually requires fewer surgical phases and tends to be a more affordable option. PMID- 28986693 TI - The prevalence of protozoa in the gut of German cockroaches (Blattella germanica) with special reference to Lophomonas blattarum. AB - The German cockroach (Blattella germanica) is a common domestic pest, which produces allergens that have been associated with broncho-pulmonary disease. Various protozoan species have been identified in the intestine of this cockroach and it has been hypothesised that these protozoa, or their proteases, may contribute to the burden of cockroach-associated allergens and adjuvants present in domestic dust. The aim of this study was therefore to determine the prevalence of protozoan species in the intestine of Blattella germanica. German cockroaches were anesthetised and dissected and gut contents are used to produce wet slides for microscopy. Both, Giemsa and Papanicolaou stains were used to confirm correct identification of Lophomonas blattarum. Representatives of four genera of protozoa were identified in 110 cockroaches: Nyctoterus sp. was observed in 91.8% of cases, Gregarina sp. in 64.5%, Amoeba sp. in 25.4% and Lophomonas blattarum in 13.6%. Nyctoterus and Gregarina were statistically significantly more likely to be found in diseased cockroaches compared to Amoeba or Lophomonas. The prevalence of Lophomonas blattarum was similar to that in published studies of a different species of cockroach, Periplaneta americana. Further work is needed to assess the interplay between protozoa, cockroaches and broncho-pulmonary diseases. PMID- 28986694 TI - Stress-related hormonal alterations, growth and pelleted starter intake in pre weaning Holstein calves in response to thermal stress. AB - This study aimed to investigate the effect of heat stress and month of birth on growth performance, pelleted starter intake, and stress-related hormones in Holstein calves. Birth weight and growth records, representing 4735 Holstein calves from a large commercial dairy herd in northern Mexico (25 degrees N; 22.3 degrees C mean annual temperature) from 2013 to 2015, were analyzed. Temperature humidity index (THI) at calving, season of birth, and month of birth were the independent variables, whereas growth traits were the dependent variables. Increased THI at birth from < 65 to > 85 units was associated with a decrease in birth weight from 39.3 to 38.7 kg. Calves subjected to high THI (> 75 units) at calving showed lesser (P < 0.01) pre-weaning gains (405 +/- 97 g/calf/day), whereas those calves born with THI < 70 units presented the highest gains (466 +/ 112 g/calf/day). Birth during the fall months reduced (P < 0.01) weaning weight by about 5 kg compared with winter months. Also, the pre-weaning average daily gain for calves born in the fall was about 70 g less (P < 0.01) than calves delivered in winter months. Plasma triiodothyronine and tetraiodothyronine levels were lower (1.02 +/- 0.21 and 48 +/- 7.9 ng/mL, respectively; P < 0.01) in summer and highest in winter (1.64 +/- 0.48 and 66 +/- 11 ng/mL, respectively). Mean plasma cortisol concentration was higher in heat-stressed calves born in summer (59 +/- 40 ng/mL) than calves born in winter (20 +/- 28 ng/mL). Pelleted starter intake 1 week before weaning was lowest (P < 0.01) in the fall (0.82 +/- 0.26 kg/calf/day; mean +/- SD) and highest in spring (1.26 +/- 0.43 kg/calf/day). It was concluded that in this particular environment, heat stress affects birth weight and growth rate of Holstein calves. Thus, environmental management of the newborn calf during hot spring and summer months is warranted to optimize pelleted starter intake and calf growth rates. PMID- 28986695 TI - Absence of DNA double-strand breaks in human peripheral blood mononuclear cells after 3 Tesla magnetic resonance imaging assessed by gammaH2AX flow cytometry. AB - OBJECTIVES: Magnetic resonance imaging (MRI) is regarded as a non-harming and non invasive imaging modality with high tissue contrast and almost no side effects. Compared to other cross-sectional imaging modalities, MRI does not use ionising radiation. Recently, however, strong magnetic fields as applied in clinical MRI scanners have been suspected to induce DNA double-strand breaks in human lymphocytes. METHODS: In this study we investigated the impact of 3-T cardiac MRI examinations on the induction of DNA double-strand breaks in peripheral mononuclear cells by gammaH2AX staining and flow cytometry analysis. The study cohort consisted of 73 healthy non-smoking volunteers with 36 volunteers undergoing CMRI and 37 controls without intervention. Differences between the two cohorts were analysed by a mixed linear model with repeated measures. RESULTS: Both cohorts showed a significant increase in the gammaH2AX signal from baseline to post-procedure of 6.7 % (SD 7.18 %) and 7.8 % (SD 6.61 %), respectively. However, the difference between the two groups was not significant. CONCLUSION: Based on our study, gammaH2AX flow cytometry shows no evidence that 3-T MRI examinations as used in cardiac scans impair DNA integrity in peripheral mononuclear cells. KEY POINTS: * No evidence for DNA double-strand breaks after cardiac MRI. * Prospective study underlines safe use of MRI with regard to DNA damage. * Controlled trial involving both genders investigating DNA DSBs after 3 T MRI. PMID- 28986696 TI - Progression level of extracapsular spread and tumor budding for cervical lymph node metastasis of OSCC. AB - OBJECTIVES: The progression level of extracapsular spread (ECS) for cervical lymph node metastasis of oral squamous cell carcinoma (OSCC) was previously divided into three types, and their relationships with the prognosis of patients were re-examined. PATIENTS AND METHODS: The Kaplan-Meier method was used to examine overall survival (OS) and relapse-free survival (RFS) curves. Prognosis factor for recurrence was analyzed with univariate and multivariate analysis. RESULTS: ECS was detected in 216 cases of OSCC and analyzed. The 5-year overall survival and RFS rates of patients with type C, which was microscopically defined as tumor invasion to perinodal fat or muscle tissue, were significantly poor at 40.6 and 37.8%, respectively. The results of a univariate analysis suggested that the prognosis of ECS in OSCC patients is associated with its progression level, particularly type C. The 5-year RFS rate of type C with tumor budding was significantly poor at 31.5%. Type C with tumor budding correlated with local and regional recurrence as well as distant metastasis. In a multivariate analysis, tumor budding was identified as an independent prognostic factor. CONCLUSIONS: These results suggest that the progression level of ECS and tumor budding are useful prognostic factors in OSCC patients. CLINICAL RELEVANCE: This study indicated that the progression level and tumor budding of ECS for cervical lymph node metastasis were useful prognostic factors in OSCC patients. PMID- 28986698 TI - Synthesis, spectroscopic characterization and in vitro anticancer activity of new platinum(II) complexes with some thione ligands in the presence of triethylphosphine. AB - Seven new platinum(II) complexes (1-7) of triethylphosphine (Et3P) and thiones (L) with general formula, cis-[Pt(Et3P)2(L)2]Cl2 were prepared and characterized by elemental analysis, FTIR and NMR (1H, 13C & 31P) measurements. The analytical and spectroscopic data suggested the formation of the desired complexes. The complexes were tested for in vitro cytotoxicity against four cell lines: Hela (human cervical adenocarcinoma), MCF-7 (human breast carcinoma), A549 (human lung carcinoma), and HTC15 (human colon carcinoma). The anticancer activity values of compounds 1-6 are much better than cisplatin and carboplatin as indicated by their IC50 values. PMID- 28986697 TI - Targeting mitochondrial function and proteostasis to mitigate dynapenia. AB - Traditionally, interventions to treat skeletal muscle aging have largely targeted sarcopenia-the age-related loss of skeletal muscle mass. Dynapenia refers to the age-related loss in skeletal muscle function due to factors outside of muscle mass, which helps to inform treatment strategies for aging skeletal muscle. There is evidence that mechanisms to maintain protein homeostasis and proteostasis, deteriorate with age. One key mechanism to maintain proteostasis is protein turnover, which is an energetically costly process. When there is a mismatch between cellular energy demands and energy provision, inelastic processes related to metabolism are maintained, but there is competition for the remaining energy between the elastic processes of somatic maintenance and growth. With aging, mitochondrial dysfunction reduces ATP generation capacity, constraining the instantaneous supply of energy, thus compromising growth and somatic maintenance processes. Further, with age the need for somatic maintenance increases because of the accumulation of protein damage. In this review, we highlight the significant role mitochondria have in maintaining skeletal muscle proteostasis through increased energy provision, protein turnover, and substrate flux. In addition, we provide evidence that improving mitochondrial function could promote a cellular environment that is conducive to somatic maintenance, and consequently for mitigating dynapenia. Finally, we highlight interventions, such as aerobic exercise, that could be used to improve mitochondrial function and improve outcomes related to dynapenia. PMID- 28986699 TI - Anisotropic mechanosensitive pathways in the diaphragm and their implications in muscular dystrophies. AB - The diaphragm is the "respiratory pump;" the muscle that generates pressure to allow ventilation. Diaphragm muscles play a vital function and thus are subjected to continuous mechanical loading. One of its peculiarities is the ability to generate distinct mechanical and biochemical responses depending on the direction through which the mechanical forces applied to it. Contractile forces originated from its contractile components are transmitted to other structural components of its muscle fibers and the surrounding connective tissue. The anisotropic mechanical properties of the diaphragm are translated into biochemical signals that are directionally mechanosensitive by mechanisms that appear to be unique to this muscle. Here, we reviewed the current state of knowledge on the biochemical pathways regulated by mechanical signals emphasizing their anisotropic behavior in the normal diaphragm and analyzed how they are affected in muscular dystrophies. PMID- 28986700 TI - Sadness and happiness are amplified in solitary listening to music. AB - Previous studies have shown that music is a powerful means to convey affective states, but it remains unclear whether and how social context shape the intensity and quality of emotions perceived in music. Using a within-subject design, we studied this question in two experimental settings, i.e. when subjects were alone versus in company of others without direct social interaction or feedback. Non vocal musical excerpts of the emotional qualities happiness or sadness were rated on arousal and valence dimensions. We found evidence for an amplification of perceived emotion in the solitary listening condition, i.e. happy music was rated as happier and more arousing when nobody else was around and, in an analogous manner, sad music was perceived as sadder. This difference might be explained by a shift of attention in the presence of others. The observed interaction of perceived emotion and social context did not differ for stimuli of different cultural origin. PMID- 28986701 TI - Mechano growth factor E peptide inhibits invasion of melanoma cells and up regulates CHOP expression via endoplasmic reticulum stress. AB - OBJECTIVE: To evaluate the effects of mechano growth factor E peptide (MGF) on the invasive properties of melanoma cells. RESULTS: Melanoma cells (GLL19) were treated with 10, 20 and 30 ng MGF/ml for 24 h. Their invasive properties were investigated by transwell assay. Cytoskeleton reorganization was assessed via staining with phalloidin-FITC; lysyl oxidase (LOX) family gene expression was tested by qRT-PCR, and western blotting was used to detect expression of the matrix metalloproteinases (MMPs) and endoplasmic reticulum (ER) stress. MGF decreased the invasive capabilities of melanoma cells and induced changes in cytoskeleton distribution. MGF also down-regulated the expression of MMPs and up regulated the expression of the cell apoptosis-related protein CHOP by inducing ER stress. CONCLUSIONS: MGF can decrease the invasive properties of melanoma cells and induce ER stress, promoting cell apoptosis. Thus, MGF represents a novel strategy for the potential treatment of patients presenting with cutaneous melanoma. PMID- 28986702 TI - A revision of the Tokuhashi revised score improves the prognostic ability in patients with metastatic spinal cord compression. AB - PURPOSE: The Tokuhashi revised score from 2005 (TR2005) is the most recommended prognostic scoring system in patients with metastatic spinal cord compression (MSCC). However, recent studies have questioned its prognostic ability and the need for a new revision has been proposed. We aimed to assess whether a revision of the TR2005 can improve the prognostic ability of the scoring system. METHODS: In 2011 and 2012, a total of 1143 consecutive patients admitted with MSCC were prospectively included in a 2011 and a 2012 cohort. For the patients admitted in 2011 (n = 544), the components of the TR2005 including primary cancer diagnosis were analyzed regarding the prognostic ability. Based on these findings, a revision of the TR2005 score was defined as the Tokuhashi revised score 2017 (TR2017). The prognostic abilities of the TR2005 and the TR2017 were compared by Kaplan Meyer (KM) curves, and receiver-operating characteristics' (ROC) analysis was compared in a cohort of patients admitted in 2012 (n = 599). RESULTS: KM curves and ROC analysis showed that the TR2017 had better prognostic ability compared to the TR2005. The ROC areas were as follows: <6-months survival, TR2017 = 0.71 and TR2005 = 0.65, and p = 0.003; for >=6-month survival, TR2017 = 0.71 and TR2005 = 0.65, and p = 0.003; for >=12-month survival TR2017 = 0.72 and TR2005 = 0.67, and p = 0.0015. CONCLUSIONS: The TR2017 can improve the prognostic ability of the TR2005 in patients with MSCC. This could affect the preoperative evaluation of patients suffering from MSCC. PMID- 28986703 TI - Relationship between baseline systolic blood pressure and long-term outcomes in acute heart failure patients treated with TRV027: an exploratory subgroup analysis of BLAST-AHF. AB - INTRODUCTION: TRV027, a 'biased' ligand of the angiotensin II type 1 receptor (AT1R), did not affect a composite clinical outcome at 30 days in a phase 2b acute heart failure (AHF) trial (BLAST-AHF). METHODS: Post-hoc analyses from BLAST-AHF (n = 618) examined the effects of TRV027 by baseline systolic blood pressure (SBP) on changes in renal function and 180-day outcomes. Interactions between baseline SBP and select endpoints were identified utilizing a subpopulation treatment effect pattern plots (STEPP) analysis, then grouping of patients by SBP tertile: < 127, >= 127 to < 140, and >= 140 mmHg. RESULTS: A trend towards increased creatinine in the first 3 days was noted in the lower SBP tertile, while in those in the higher two tertiles, TRV027, especially the 1 mg/h dose, reduced creatinine at days 5 and 30. Beneficial effects on 180-day all cause mortality and cardiovascular (CV) death or readmission were observed in the two higher SBP tertiles (SBP >= 127 mmHg) in the TRV027 1 mg/h dose group (all cause mortality HR 0.39, 95% CI 0.14-1.06, p = 0.056; CV death or HF/RF rehospitalization HR 0.53, 95% CI 0.28-1.01, p = 0.049), while more adverse outcomes were observed in patients in the lower SBP tertile. CONCLUSIONS: This post-hoc analysis of the BLAST-AHF study suggests contrasting effects of TRV027 by baseline SBP, with trends towards lower 180-day event rates in patients enrolled with higher baseline SBP, especially when given lower doses of TRV027. PMID- 28986704 TI - Bidirectional mediation of depression and pain intensity on their associations with upper extremity physical function. AB - Pain intensity and symptoms of depression are correlated and individually associated with decreased physical function. We compared two explanatory mediation models; one with depression as mediator of the association of pain intensity with physical function and the other one with pain intensity as the mediator of the effect of depression on physical function. In a cross-sectional study, 102 patients with upper extremity musculoskeletal illness completed measures of pain intensity, PROMIS depression CAT, PROMIS physical function-upper extremity CAT and demographics. We determined that pain intensity and symptoms of depression were partial mediators of their respective and independent effects on physical function. While depression had a larger standardized mediation effect and a bigger kappa-squared (kappa 2) effect size compared to pain intensity, the actual proportion of variance in physical function that could be explained by the mediated effects (i.e., R 2 mediation effect size) was equal in both models suggesting that the two mediation models have equal ability to explain variations in physical function. The bidirectional mediation effect suggests a reinforcement mechanism, in which, pain intensity and symptoms of depression reciprocally influence their negative impacts on physical function among patients with musculoskeletal illness. PMID- 28986705 TI - Rescue therapy with alemtuzumab in multiple sclerosis post-natalizumab puerperium reactivation. PMID- 28986707 TI - Understanding Homosexuality: Moving on from Patterns to Mechanisms. PMID- 28986706 TI - Enhancement of photo-bactericidal effect of tetrasulfonated hydroxyaluminum phthalocyanine on Pseudomonas aeruginosa. AB - At the present time, photodynamic inactivation (PDI) is receiving considerable interest for its potential as an antimicrobial therapy. The results of our study indicate that enhancement of the phototoxic effect on Pseudomonas aeruginosa can be achieved by combination of tetrasulfonated hydroxyaluminum phthalocyanine (AlPcS4) and bimetallic gold/silver nanoparticles (Au/Ag-NPs) synthesized by the cell-free filtrate of Aureobasidium pullulans. The bimetallic nanoparticles were characterized by a number of techniques including UV-vis, XPS, TEM, and SEM-EDS to be 14 +/- 3 nm spherical particles coated with proteins. The effect of diode lasers with the peak-power wavelength y = 650 nm (output power of 10 and 40 mW; radiation intensity of 26 and 105 mW/cm2) in combination with the AlPcS4 and the bimetallic nanoparticles mixture on the viability of P. aeruginosa rods was shown. Particularly high efficiency of killing bacterial cells was obtained for the light intensity of 105 mW/cm2, after 20, 30, and 40 min of irradiation corresponding to 126, 189, and 252 J/cm2 energy fluences. For AlPcS4+Au/Ag-NPs treatment, the viable count reduction were equal to 99.90, 99.96, and 99.975%, respectively. These results were significantly better than those accomplished for irradiated separated assays of AlPcS4 and Au/Ag-NPs. PMID- 28986708 TI - Hypersexuality: Equifinal, Cohesive, Clinical Presentation or Symptom Cluster with Multiple Underlying Mechanisms? PMID- 28986709 TI - Uterine artery pseudoaneurysm in the setting of deep endometriosis: an uncommon cause of hemoperitoneum in pregnancy. AB - Uterine, ovarian, and placental pathologies are among the differential considerations for a pregnant woman presenting with abdominal and pelvic pain. Imaging plays a key role in the initial work-up of these patients. Sonography is often the first line test; however, evaluation of pelvic pathology can be limited in the gravid state, especially in mid- or late-term pregnancy. We present a case of a pregnant woman who came to the emergency room at 25 weeks with acute abdominal and pelvic pain. Both ultrasound and MR imaging findings revealed intraperitoneal hemorrhage, initially of unknown origin, as well as endometriomas and deep endometriosis. Only postpartum imaging confirmed a uterine artery pseudoaneurysm (PSA) presumably due to decidual reaction in deep endometriosis. We speculate the intraperitoneal hemorrhage was subsequently due to the PSA. This case demonstrates that if hemorrhage is not recognized promptly, it can lead to hemodynamic instability, as well as premature labor and delivery. PMID- 28986710 TI - Scientism in Medical Education and the Improvement of Medical Care: Opioids, Competencies, and Social Accountability. AB - Scientism in medical education distracts educators from focusing on the content of learning; it focuses attention instead on individual achievement and validity in its measurement. I analyze the specific form that scientism takes in medicine and in medical education. The competencies movement attempts to challenge old "scientistic" views of the role of physicians, but in the end it has invited medical educators to focus on validity in the measurement of individual performance for attitudes and skills that medicine resists conceptualizing as objective. Academic medicine should focus its efforts instead on quality and relevance of care. The social accountability movement proposes to shift the focus of academic medicine to the goal of high quality and relevant care in the context of community service and partnership with the institutions that together with medicine create and cope with health and with health deficits. I make the case for this agenda through a discussion of the linked histories of the opioid prescribing crisis and the professionalism movement. PMID- 28986711 TI - Blockade of LGR4 inhibits proliferation and odonto/osteogenic differentiation of stem cells from apical papillae. AB - During tooth root development, stem cells from apical papillae (SCAPs) are indispensable, and their abilities of proliferation, migration and odontoblast differentiation are linked to root formation. Leucine-rich repeat-containing GPCR 4 (LGR4) modulates the biological processes of proliferation and differentiation in multiple stem cells. In this study, we showed that LGR4 is expressed in all odontoblast cell lineage cells and Hertwig's epithelial root sheath (HERS) during the mouse root formation in vivo. In vitro we determined that LGR4 is involved in the Wnt/beta-catenin signaling pathway regulating proliferation and odonto/osteogenic differentiation of SCAPs. Quantitative reverse-transcription PCR (qRT-PCR) confirmed that LGR4 is expressed during odontogenic differentiation of SCAPs. CCK8 assays and in vitro scratch tests, together with cell cycle flow cytometric analysis, demonstrated that downregulation of LGR4 inhibited SCAPs proliferation, delayed migration and arrested cell cycle progression at the S and G2/M phases. ALP staining revealed that blockade of LGR4 decreased ALP activity. QRT-PCR and Western blot analysis demonstrated that LGR4 silencing reduced the expression of odonto/osteogenic markers (RUNX2, OSX, OPN, OCN and DSPP). Further Western blot and immunofluorescence studies clarified that inhibition of LGR4 disrupted beta-catenin stabilization. Taken together, downregulation of LGR4 gene expression inhibited SCAPs proliferation, migration and odonto/osteogenic differentiation by blocking the Wnt/beta-catenin signaling pathway. These results indicate that LGR4 might play a vital role in SCAPs proliferation and odontoblastic differentiation. PMID- 28986712 TI - Regulation of Fatty Acid Production and Release in Benthic Algae: Could Parallel Allelopathy Be Explained with Plant Defence Theories? AB - Many organisms produce chemical compounds, generally referred as secondary metabolites, to defend against predators and competitors (allelopathic compounds). Several hypotheses have been proposed to explain the interaction between environmental factors and secondary metabolites production. However, microalgae commonly use simple metabolites having a role in primary metabolism as allelopathic compounds. The aim of this study was to determine whether classical theories of plant chemical defences could be applied to microalgae producing allelochemicals derived from the primary metabolism. Our study was designed to investigate how growth phase, algal population density, nutrient limitation and carbon assimilation affect the production and release of allelopathic free fatty acids (FFAs) among other FFAs. The model species used was Uronema confervicolum, a benthic filamentous green alga that produces two allelopathic FFAs (linoleic and alpha-linolenic acids) inhibiting diatom growth. FFAs have been quantified in algal biomass and in culture medium. Our results were analysed according to two classical plant defence theories: the growth-differentiation balance hypothesis (GDBH) and the optimal defence theory (ODT), based on the metabolic capacities for defence production and on the need for defence, respectively. While a higher production of allelopathic compounds under increased light conditions supports the use of GDBH with this microalga, the observation of a negative feedback mechanism mostly supports ODT. Therefore, both theories were insufficient to explain all the observed effects of environmental factors on the production of these allelochemicals. This highlights the needs of new theories and models to better describe chemical interactions of microalgae. PMID- 28986713 TI - Best practices for naming, receiving, and managing cells in culture. AB - One of the first considerations in using an existing cell line or establishing a new a cell line is the detailed proactive planning of all phases of the cell line management. It is necessary to have a well-trained practitioner in best practices in cell culture who has experience in receiving a new cell line into the laboratory, the correct and appropriate use of a cell line name, the preparation of cell banks, microscopic observation of cells in culture, growth optimization, cell count, cell subcultivation, as well as detailed protocols on how to expand and store cells. Indeed, the practitioner should best manage all activities of cell culture by ensuring that the appropriate certified facilities, equipment, and validated supplies and reagents are in place. PMID- 28986714 TI - Comparison of antiretroviral drug resistance among treatment-naive and treated HIV-infected individuals in Shiraz, Iran. AB - The use of anti-retroviral therapy has been effective in controlling the spread of HIV-1, and has prolonged life expectancy, but this success can be affected by the emergence of drug resistance. The main goal of this study was to investigate drug resistance in the reverse transcriptase (RT), and protease (PR) genes among HIV-1 infected individuals. We systematically selected 59 HIV-1 infected individuals from Shiraz Voluntary Counseling and Testing Center (29 treatment- naive and 30 treated). In this study intravenous drug users older than 18 were included in this study. Using specific primers, nested RT-PCR was performed on RNA extracted from patient samples. The genes targeted for RT and PCR were successfully amplified and sequenced. The sequences of these two genes were compared with mutations related to drug resistance against nucleotide reverse transcriptase inhibitors (NRTI), non-nucleotide reverse transcriptase inhibitors (NNRTI) and protease inhibitors (PI) using the latest database from the International AIDS society - USA, Stanford University, and the patterns were recorded. Among treatment-naive, the detected NRTI and NNRTI resistance mutations were V179T, V75 M and E138A. V179T causes high level resistance to Efavirenze and Nevirapin. V75 M causes intermediate resistance to Stavudine. Regarding NRTI and NNRTI resistance mutations among treated patients, the most frequent mutation (7%) was M184 V, which causes high level resistance to zidovudin and emtricitabine. The interesting result from this study was the detection of NRTI and NNRTI resistance mutations before the initiation of treatment, which signifies the transmission of resistant strains of virus between individuals. This mutation highlights the importance of drug resistance HIV-1 genotyping before commencing treatment. PMID- 28986715 TI - Induction therapy of basiliximab versus antithymocyte globulin in renal allograft: a systematic review and meta-analysis. AB - OBJECTIVE: The aim of this meta-analysis was to evaluate the efficacy of basiliximab versus antithymocyte globulin for induction therapy in renal allograft. METHODS: Medline (PubMed), Embase, Ovid, Cochrane, and the Chinese Biomedical Literature databases were searched to identify prospective randomized controlled trials that compared basiliximab with antithymocyte globulin (ATG) for induction therapy in renal transplantation. RevMan 5.1 software and Stat Manager V4.1 software were used for the meta-analysis. RESULTS: Eight RCTs were included, including a total of 1153 patients. Of these, 547 (47%) had received basiliximab, and 606 (53%) had received ATG. The pooled results revealed that the basiliximab had a lower rate of neoplasm compared with ATG [odds ratio (OR) 0.26; 95% confidence interval (CI) 0.08-0.78; P = 0.02]. There were no significant differences between the two drugs regarding 1-year acute rejection rate (OR 1.32; 95% CI 0.93-1.87; P = 0.13), 1-year graft survival rate (OR 0.73; 95% CI 0.45 1.18; P = 0.20), 1-year patient survival rate (OR 0.52; 95% CI 0.27-1.02; P = 0.06), 1-year infection rate (OR 0.90; 95% CI 0.48-1.68; P = 0.73). CONCLUSION: Induction therapy of basiliximab has similar short-time effects on the recipients in renal transplantation compared with that of ATG. However, regarding the long term effect, as represented by the rate of neoplasm, basiliximab has a significant advantage. PMID- 28986717 TI - Synthesis and Spectroscopic Studies of Phenanthroimidazole-Imine Derivatives and Evaluation of Their Antioxidant Activity. AB - The phenanthroimidazole derivatives are used in the drug industry in large scale. In this study four new phenanthroimidazole-imine derivatives were synthesized and their spectroscopic studies as well as their antioxidant behaviors were examined. Structural analyses were made by FT-IR, 1H-NMR, 13C-NMR, LC-MS spectroscopy techniques. UV-vis absorption and emission spectroscopy techniques have been used to determine the photophysical characteristics of four newly synthesized phenanthroimidazoles. The maximum absorption and emission wavelengths, molar extinction coefficients (epsilon), singlet energy levels (Es), Stokes' shift values (Deltalambda) of phenanthroimidazole-imine derivatives are given. Additionally, the antioxidant behavior of all compounds were investigated which the ascorbic acid used as standard molecule in present study. PMID- 28986716 TI - Cirrhosis Is Associated with Increased Mortality in Patients with Diverticulitis: A Nationwide Cross-Sectional Study. AB - BACKGROUND: Diverticulitis in patients with cirrhosis has been associated with higher surgical mortality, but no prior studies evaluate non-surgical treatment results. AIMS: Our aim was to compare the outcomes of hospitalization for diverticulitis in patients with and without cirrhosis. METHODS: We utilized the Nationwide Inpatient Sample (2007-2013) for patients with and without cirrhosis hospitalized for diverticulitis. Patients were further stratified by the presence of compensated versus decompensated cirrhosis. Validated ICD-9 codes captured patients and surgical procedures. Multivariate logistic regression models were fit. The primary outcomes of interest were mortality and surgical intervention rates. RESULTS: There were 1,555,469 patients hospitalized for diverticulitis without cirrhosis, and 7523 patients hospitalized for diverticulitis with cirrhosis. On multivariate analysis, patients with cirrhosis had an increased mortality rate (OR 2.28; 95% CI 1.48-3.5). There were no significant differences in surgical interventions. Subgroup multivariate analyses of compensated cirrhosis (n = 6170) and decompensated cirrhosis (n = 1353) revealed that decompensated cirrhosis had an increased mortality rate (OR 4.99; 95% CI 2.48 10.03) when compared to patients without cirrhosis, whereas those with compensated cirrhosis did not (OR 1.67; 95% CI 0.96-2.91). Those with compensated cirrhosis underwent less surgical interventions (OR 0.82; 95% CI 0.67-0.99) compared to those without cirrhosis. Patients with diverticulitis and cirrhosis had increased costs and lengths of hospitalization. CONCLUSION: Presence of cirrhosis in patients hospitalized for diverticulitis is associated with an increased mortality rate. These are novel findings, and future clinical studies should focus on improving diverticulitis outcomes in this group. PMID- 28986718 TI - Frontal Lobe Connectivity and Network Community Characteristics are Associated with the Outcome of Subthalamic Nucleus Deep Brain Stimulation in Patients with Parkinson's Disease. AB - Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is nowadays an evidence-based state of the art therapy option for motor and non-motor symptoms in patients with Parkinson's disease (PD). However, the exact anatomical regions of the cerebral network that are targeted by STN-DBS have not been precisely described and no definitive pre-intervention predictors of the clinical response exist. In this study, we test the hypothesis that the clinical effectiveness of STN-DBS depends on the connectivity profile of the targeted brain networks. Therefore, we used diffusion-weighted imaging (DWI) and probabilistic tractography to reconstruct the anatomical networks and the graph theoretical framework to quantify the connectivity profile. DWI was obtained pre-operatively from 15 PD patients who underwent DBS (mean age = 67.87 +/- 7.88, 11 males, H&Y score = 3.5 +/- 0.8) using a 3T MRI scanner (Philips Achieva). The pre-operative connectivity properties of a network encompassing frontal, prefrontal cortex and cingulate gyrus were directly linked to the postoperative clinical outcome. Eccentricity as a topological-characteristic of the network defining how cerebral regions are embedded in relation to distant sites correlated inversely with the applied voltage at the active electrode for optimal clinical response. We found that network topology and pre-operative connectivity patterns have direct influence on the clinical response to DBS and may serve as important and independent predictors of the postoperative clinical outcome. PMID- 28986719 TI - 2D vs. 3D imaging in laparoscopic surgery-results of a prospective randomized trial. AB - PURPOSE: 3D imaging is an upcoming technology in laparoscopic surgery, and recent studies have shown that the modern 3D technique is superior in an experimental setting. However, the first randomized controlled clinical trial in this context dates back to 1998 and showed no significant difference between 2D and 3D visualization using the first 3D generation technique, which is now more than 15 years old. METHODS: Positive results measured in an experimental setting considering 3D imaging on surgical performance led us to initiate a randomized controlled pragmatic clinical trial to validate our findings in daily clinical routine. Standard laparoscopic operations (cholecystectomy, appendectomy) were preoperatively randomized to a 2D or 3D imaging system. We used a surgical comfort scale (Likert scale) and the Raw NASA Workload TLX for the subjective assessment of 2D and 3D imaging; the duration of surgery was also measured. RESULTS: The results of 3D imaging were statistically significant better than 2D imaging concerning the parameters "own felt safety" and "task efficiency"; the difficulty level of the procedures in the 2D and 3D groups did not differ. Overall, the Raw NASA Workload TLX showed no significance between the groups. CONCLUSION: 3D imaging could be a possible advantage in laparoscopic surgery. The results of our clinical trial show increased personal felt safety and efficiency of the surgeon using a 3D imaging system. Overall of the procedures, the findings assessed using Likert scales in terms of own felt safety and task efficiency were statistically significant for 3D imaging. The individually perceived workload assessed with the Raw NASA TLX shows no difference. Although these findings are subjective impressions of the performing surgeons without a clear benefit for 3D technology in clinical outcome, we think that these results show the capability that 3D laparoscopy can have a positive impact while performing laparoscopic procedures. PMID- 28986720 TI - The Role of Metabolic Surgery in Non-alcoholic Steatohepatitis Improvement. AB - PURPOSE OF REVIEW: Non-alcoholic fatty liver disease (NAFLD) is frequently associated with obesity and overweight. It has a broad spectrum of clinical and histological presentations, such as steatosis, inflammation (known as non alcoholic steatohepatitis or NASH), fibrosis, and cirrhosis. There is increasing evidence that marked weight loss following bariatric surgery is associated with NASH resolution; however, little is known about the mechanisms that may lead to this beneficial condition and if it is due to weight loss alone. In this review, the authors present the latest data regarding NASH resolution following metabolic surgery and try to answer the following questions: is NASH resolution due to weight loss alone or is it related to weight-independent effects similarly to T2D? In such case, can NASH be considered as a sole criterion for metabolic surgery? RECENT FINDINGS: Most data evaluating NAFLD and bariatric and metabolic surgery are derived from cohort studies. Available data are extremely variable, but in general show a dramatic regression of steatosis, inflammatory changes, and in some cases even fibrosis that is probably linked to major weight loss following surgery. There are no randomized controlled trials evaluating the effects of metabolic surgery over NASH vs. lifestyle modifications. To consider NASH a sole indication for metabolic surgery regardless of BMI, such studies are desperately needed and should be the primary focus of future research in metabolic surgery. PMID- 28986721 TI - Does trade matter for carbon emissions in OECD countries? Evidence from a new trade openness measure. AB - This paper analyzes the impacts of the per capita income, the per capita energy consumption, and the trade openness on the level of per capita carbon emissions in the panel dataset of 35 Organization for Economic Cooperation and Development (OECD) countries over the period 1960-2013. Along with the nominal trade openness, the paper uses a different trade openness measure, so called as the "trade potential index" (TPI). To the best of our knowledge, this is the first paper that uses the TPI in the empirical environmental Kuznets curve (EKC) hypothesis literature. The paper finds that the EKC hypothesis is valid and there is an "inverted-U" relationship between the income and the carbon emissions. In addition, the paper observes that there is a positive effect of the energy consumption on the carbon emissions. Furthermore, the results indicate that both trade openness measures are negatively associated with the carbon emissions in the OECD countries in the long run. PMID- 28986722 TI - Impact of the National Cervical Screening Programme in New Zealand by age: analysis of cervical cancer trends 1985-2013 in all women and in Maori women. AB - BACKGROUND: New Zealand is an example of a country with a well-established cytology-based screening program. New Zealand's National Cervical Screening Programme (NCSP) commenced in 1990, and recommends three-yearly cytology-based screening for women aged 20-69 years. In 2018, the NCSP will transition to five yearly HPV-based screening for women aged 25-69 years. The aim of this study was to assess the impact of the program to date in different groups, to provide a benchmark for the new program. METHODS: Analysis of cervical cancer trends in New Zealand by age and ethnicity over the period 1985-2013, and by morphology over the period 1997-2013, using data from the New Zealand Cancer Registry was conducted. RESULTS: The overall incidence of cervical cancer was 56% (95% CI 51 60%) lower in 2009-2013 than in 1985-1989, and significant reductions were observed in women aged 25-49, 50-69, and 70 + years. Relative reductions in cervical cancer were very similar for Maori and non-Maori women aged 25-49 (50% in Maori; 52% in non-Maori) and 50-69 years (65% in Maori; 69% in non-Maori). In contrast, incidence appeared to increase after around 1996 in women aged 20-24. The increasing trend was significant for women aged 20-24 overall and for non Maori women (p < 0.01 in both cases). CONCLUSION: There have been substantial reductions in cervical cancer among women aged 25 + years in New Zealand since the inception of the NCSP, and these reductions are similar in Maori and non Maori women. Cervical cancer incidence among women 20-24 years has not declined since the NCSP began, and appears to be increasing. PMID- 28986723 TI - Characterization and Separation of Cancer Cells with a Wicking Fiber Device. AB - Current cancer diagnostic methods lack the ability to quickly, simply, efficiently, and inexpensively screen cancer cells from a mixed population of cancer and normal cells. Methods based on biomarkers are unreliable due to complexity of cancer cells, plasticity of markers, and lack of common tumorigenic markers. Diagnostics are time intensive, require multiple tests, and provide limited information. In this study, we developed a novel wicking fiber device that separates cancer and normal cell types. To the best of our knowledge, no previous work has used vertical wicking of cells through fibers to identify and isolate cancer cells. The device separated mouse mammary tumor cells from a cellular mixture containing normal mouse mammary cells. Further investigation showed the device separated and isolated human cancer cells from a heterogeneous mixture of normal and cancerous human cells. We report a simple, inexpensive, and rapid technique that has potential to identify and isolate cancer cells from large volumes of liquid samples that can be translated to on-site clinic diagnosis. PMID- 28986725 TI - Arsenic in the health of ecosystems: spatial distribution in water, sediment and aquatic biota of Pampean streams. AB - A survey of arsenic and phosphorus in Pampean streams of Buenos Aires province was performed. Nitrates and ammonia were also determined. Stream water was sampled as well as stream sediment and filamentous algae. Results show that 32 streams exceeded the arsenic recommended guidelines for human consumption of 10 MUg L-1 and six exceeded recommended values for aquatic organisms' protection of 50 MUg L-1. The average concentration found was 36.54 MUg L-1 and areas with more concentration of As are located in the southern region of the province, in streams that are tributaries of the Atlantic Ocean. Other regions with high As concentration are the Matanza River tributaries and the Arrecifes River tributaries. No differences of As concentration was found between stream sediments. Also, no seasonal pattern of As concentration was observed in one stream sampled during a year, but a positive correlation between As and the conductivity (p = 0.0002) and pH (p = 0.01) of the streams was found. Also, As bioaccumulation was detected for all the algae sampled, but no correlation between As accumulated and As in the stream water was found. Ammonia levels exceeded recommended guidelines for human consumption in the Argentinean law in 30 streams. The characterization performed in this study provides relevant information on the distribution of arsenic and its origin and mobility. PMID- 28986726 TI - Acute pancreatitis-onset carcinoma in situ of the pancreas with focal fat replacement diagnosed using serial pancreatic-juice aspiration cytologic examination (SPACE). AB - A 59-year-old woman was admitted for acute pancreatitis. Abdominal computed tomography and magnetic resonance imaging revealed a swollen pancreatic parenchyma with dilatation of the main pancreatic duct (MPD) of the pancreas tail, which was separated from the normal pancreas body side by a locally atrophic part of the pancreas. Magnetic resonance cholangiopancreatography showed MPD stricture in the pancreas tail with dilatation of the upstream MPD. Endoscopic ultrasonography revealed that the MPD stricture of the pancreas tail was surrounded by a blurred and hypoechoic area. Endoscopic retrograde cholangiopancreatography was performed for serial pancreatic-juice aspiration cytologic examination (SPACE). The result indicated adenocarcinoma. Distal pancreatectomy was performed, and the histopathological examination showed high grade PanIN (carcinoma in situ of the pancreatic duct) of the pancreas tail with atrophy and fibrosis of the pancreatic parenchyma, and local fat replacement adjacent to the lesion. The final histopathological diagnosis was carcinoma in situ of the pancreatic duct of the pancreas tail. Acute pancreatitis and local fatty change of the pancreatic parenchyma with MPD stricture are important clinical manifestations of pancreatic carcinoma in situ (PCIS) and performing SPACE in cases of MPD stricture without a recognizable mass is preferable for a diagnosis of PCIS. PMID- 28986724 TI - Progestin is important for testicular development of male turbot (Scophthalmus maximus) during the annual reproductive cycle through functionally distinct progestin receptors. AB - In teleost, sex steroid hormones are critical for reproduction. Progestin is known to promote spermiation. To further understand the functions of progestin via its receptors during the annual reproductive cycle in male turbot (Scophthalmus maximus), we observed testicular development, quantified several sex steroid hormones, detected the expression of progestin receptors, and measured various sperm parameters. Results showed that the turbot testicular structure was of the lobular type. During breeding season, a number of spermatocytes (stage III) developed into spermatids (stage IV), then differentiated into sperm during spermiogenesis (stage V), and finally regressed to spermatocytes (stage VI). Concomitant with testicular development, serum progesterone (P4) and 17alpha,20beta-dihydroxy-4-pregnen-3-one (DHP) exhibited higher levels from stage IV to V than other stages. Furthermore, males with higher motility sperm showed higher levels of P4 and DHP compared with fish with lower motility sperm. These results indicated that P4 and DHP might induce spermatogenesis due to seasonal changes. Concurrently, in testes, the nuclear progesterone receptor (pgr) was expressed throughout the reproductive cycle and its level peaked during spermiogenesis while expression of membrane progestin receptor alpha (mPRalpha) did not change significantly. However, in sperm, mPRalpha expression was higher than in testes and had a significant positive correlation with curvilinear velocities (VCL), sperm motility, and motility duration. In conclusion, progestin appears to exert a direct pgr-mediated effect on spermiogenesis and improve sperm motility characteristics depending on the abundance of mPRalpha protein in sperm during spermiation. PMID- 28986728 TI - Comments on "Mapping the scientific research on non-point source pollution: a bibliometric analysis" by Yang et al. (2017). PMID- 28986727 TI - DPP-4 inhibitors and heart failure: a potential role for pharmacogenomics. AB - There remains an ongoing controversy regarding the safety of dipeptidyl peptidase 4 (DPP-4) inhibitors and the risk of developing heart failure (HF). In addition, none of the animal studies suggested a mechanism for the DPP-4 inhibitors and HF risk. To date, advances in pharmacogenomics have enabled the identification of genetic variants in DPP-4 gene. Studies have shown that genetic polymorphisms in the gene encoding DPP-4 may be associated with potential pathways involved in HF risk. This review discusses the contradictory findings of DPP-4 inhibitors and HF and a potential role for pharmacogenomics. Pharmacogenomics of DPP-4 inhibitors is promising, and genetic information from randomized control trials is urgently needed to gain a full understanding of the safety of DPP-4 inhibitors and the risk of HF. PMID- 28986729 TI - Impact of waste dump on surface water quality and aquatic insect diversity of Deepor Beel (Ramsar site), Assam, North-east India. AB - Water and aquatic insects were collected seasonally from site 1, the low-lying area of the dump near Deepor Beel, and from sites 2 and 3 of the main wetland and analysed. While dissolved oxygen (DO) increased from site 1 to site 3 in each season, electrical conductivity (EC), total dissolved solid (TDS), total alkalinity (TA) and free CO2 (F-CO2) decreased. Pb and Cd were found to exceed the limits set for drinking water in all the sites and seasons. Species richness (SpR) was found highest (23) at site 2 and lowest (14) at site 1. Sensitive species was absent. The Shannon (H') values at site 1 were < 1 while at sites 2 and 3 were > 1 in most of the seasons. Biological monitoring scores (Biological Monitoring Working Party and Stream Invertebrate Grade Number-Average Level) in different sites and seasons inferred severely poor to moderate water quality. At site 1, significant negative correlations were seen for Pb and Cr with SpR while Ni and Cu with insect density (ID). At site 2, TA had highly significant positive correlations with SpR and ID while Cu showed negative correlation with SpR. At site 3, ID had significant negative relationships with air temperature, water temperature, depth, TA, F-CO2, PO43- and Cr. Canonical correspondence analysis triplot has clearly separated site 1 associated with tolerant species and highly influenced by TA, TDS, EC, F-CO2, Cr, Ni, Cd and Zn confirming high anthropogenic activities on that site. Tolerant and semitolerant species were present at site 2 (influenced by depth and transparency) and site 3 (influenced by Pb and WT) both. Results of this study discerned that the dump site is the point source of pollution. PMID- 28986731 TI - Successful management of prolonged venovenous extracorporeal membrane oxygenation in an octogenarian. AB - Venovenous extracorporeal membrane oxygenation is now an established treatment for acute respiratory distress syndrome. However, this treatment remains rare in octogenarians and is associated with poor outcomes. An 81-year-old man with a history of chronic obstructive pulmonary disease and heavy smoking underwent mitral and tricuspid valve repair and the Maze procedure for mitral and tricuspid regurgitation and paroxysmal atrial fibrillation. Although he was extubated the following day, his postoperative course was complicated with pneumonia followed by acute respiratory distress syndrome. He was reintubated on day 7. Ratio of partial pressure of arterial oxygen to fraction of inspired oxygen continuously dropped to less than 100 mmHg, and venovenous extracorporeal membrane oxygenation support was induced on day 18. His lung condition showed slow and steady recovery, and he was successfully weaned from mechanical support on day 44 (total support, 27 days). Bleeding complication from tracheotomy (day 31) due to disseminated intravascular coagulation was successfully managed using recombinant human soluble thrombomodulin. He was ambulatory and discharged to a nursing facility without tracheotomy on day 172. Proper extracorporeal membrane oxygenation management, while challenging to keep the elderly patient away from further complications, saved an 81-year-old patient. PMID- 28986730 TI - Acute hantavirus infection presenting as haemolytic-uraemic syndrome (HUS): the importance of early clinical diagnosis. AB - The European prototype of hantavirus, Puumala virus (PUUV), isolated from a common wild rodent, the bank vole (Myodes glareolus), causes nephropathia epidemica (NE). NE can perfectly mimic haemolytic-uraemic syndrome (HUS), progressing from an aspecific flu-like syndrome to acute kidney injury with thrombocytopaenia, and presenting with some signs of haemolytic anaemia and/or coagulopathy. Moreover, both NE and HUS can occur in local outbreaks. We report an isolated case of NE, initially referred for plasmapheresis for suspected HUS, although signs of overt haemolysis were lacking. Early suspicion of hantavirus infection, later confirmed by serology and reverse transcription polymerase chain reaction (RT-PCR), prevented subsequent excessive treatment modalities. PMID- 28986732 TI - Manipulation of nitrogen leaching from tea field soil using a Trichoderma viride biofertilizer. AB - With the increasing use of chemical fertilizers, negative environmental impacts have greatly increased as a result from agricultural fields. The fungus Trichoderma viride used as a biofertilizer can efficiently reduce nitrous oxide (N2O) emissions from subtropical tea fields in southern China. In this paper, it was further found that T. viride biofertilizer could alleviate nitrogen (N) leaching in tea fields. Gross N leaching was 1.51 kg ha-1 year-1 with no external fertilizer input, but when 225 kg N ha-1 year-1was applied, it increased to 12.38 kg ha-1 year-1 using T. viride biofertilizer but 53.46 kg ha-1 year-1 using urea. Stepwise linear regression analysis identified the factors responsible for N leaching to be soil nitrate concentration and soil interflow, simulated here using the water balance simulation model (WaSiM-ETH). Finally, mass-scale production of T. viride biofertilizer from waste reutilization using sweet potato starch wastewater and rice straw was found to be cost-effective and feasible. These procedures could be considered a best management practice to reduce N leaching from tea fields in subtropical areas of central China and to reduce pollution from other agricultural waste products. PMID- 28986733 TI - Workflows and performances in the ranking prediction of 2016 D3R Grand Challenge 2: lessons learned from a collaborative effort. AB - The 2016 D3R Grand Challenge 2 includes both pose and affinity or ranking predictions. This article is focused exclusively on affinity predictions submitted to the D3R challenge from a collaborative effort of the modeling and informatics group. Our submissions include ranking of 102 ligands covering 4 different chemotypes against the FXR ligand binding domain structure, and the relative binding affinity predictions of the two designated free energy subsets of 15 and 18 compounds. Using all the complex structures prepared in the same way allowed us to cover many types of workflows and compare their performances effectively. We evaluated typical workflows used in our daily structure-based design modeling support, which include docking scores, force field-based scores, QM/MM, MMGBSA, MD-MMGBSA, and MacroModel interaction energy estimations. The best performing methods for the two free energy subsets are discussed. Our results suggest that affinity ranking still remains very challenging; that the knowledge of more structural information does not necessarily yield more accurate predictions; and that visual inspection and human intervention are considerably important for ranking. Knowledge of the mode of action and protein flexibility along with visualization tools that depict polar and hydrophobic maps are very useful for visual inspection. QM/MM-based workflows were found to be powerful in affinity ranking and are encouraged to be applied more often. The standardized input and output enable systematic analysis and support methodology development and improvement for high level blinded predictions. PMID- 28986734 TI - Antral follicle responsiveness to FSH, assessed by the follicular output rate (FORT), is altered in Hodgkin's lymphoma when compared with breast cancer candidates for fertility preservation. AB - PURPOSE: Oocyte and/or embryo cryopreservation after controlled ovarian hyperstimulation (COH) represents the most established method for female fertility preservation (FP) before cancer treatment. Whether patients suffering from malignancies, candidates for FP, have a normal ovarian capacity to respond to stimulation is controversial. Reduced responsiveness of antral follicle to exogenous FSH might be at play. The percentage of antral follicles that successfully respond to FSH administration may be estimated by the follicular output rate (FORT), which presumably reflects the health of granulosa cells. The present study aims at investigating whether the FORT differs between Hodgkin's lymphoma (HL) and breast cancer (BC) patients. METHODS: Forty-nine BC and 33 HL patient candidates for FP using oocyte vitrification following COH were prospectively studied. FORT was calculated by the ratio between the pre-ovulatory follicle count (16-22 mm) on the day of oocyte triggering * 100/antral follicle count before initiation of the stimulation. RESULTS: Overall, women in the HL group were younger in comparison with BC patients (26.4 +/- 3.9 vs 33.6 +/- 3.3 years, p < 0.0001, respectively). The FORT was significantly decreased in patients with HL when compared with BC group (27.0 +/- 18.8 vs 39.8 +/- 18.9%, p = 0.004, respectively), further leading to a comparable number of oocytes vitrified (10.8 +/- 5.9 vs 10.2 +/- 7.7 oocytes, p = 0.7, respectively). CONCLUSION: The present findings indicate that the percentage of antral follicles that successfully respond to FSH administration is reduced in HL when compared to BC patients, supporting the hypothesis of a detrimental effect of hemopathy on follicular health. In vitro experimentations might provide additional data to confirm this hypothesis. PMID- 28986735 TI - NO2 inhalation enhances asthma susceptibility in a rat model. AB - Nitrogen dioxide (NO2) is a major air pollutant. Epidemiologic studies have found that NO2 exposure is associated with an increased risk of asthma. Nevertheless, the potential molecular mechanisms remain unclear. In this study, we investigated the effect of NO2 inhalation on the occurrence of allergic airway inflammation and its underlying mechanisms. Firstly, male Wistar rats were exposed to 2 and 5 mg/m3 NO2 (28 days, 5 h/day). The results showed that NO2 exposure could induce pulmonary inflammatory response, mucus formation, and Th1/Th2 imbalance in the lung of normal rats, resulting in allergic asthma-like features. Secondly, male Wistar rats were exposed to 5 mg/m3 NO2 (42 days, 5 h/day), sensitized with ovalbumin (OVA), challenged with aerosolized OVA, and characterized in asthma models. Results showed that NO2 exposure aggravated lung inflammation in the OVA sensitized rats, accompanied by the increase in inflammatory cell infiltration, mucus hypersecretion, and collagen deposition. Furthermore, NO2 exposure promoted the increase in the expression of mucin gene (MUC5AC) and pro-inflammatory factors [interleukin (IL)-1beta, intercellular adhesion molecule-1 (ICAM-1), and IL-6] as well as serum OVA-specific immunoglobulin E (IgE) production. Taken together, we established that NO2 exposure promotes allergic airway inflammation and increases the asthma susceptibility. The underlying mechanisms involve the promotion of activation of interleukin-4/signal transducer and activator of transcription-6 (IL-4/STAT6) pathway [IL-4 receptor (IL-4R) alpha, janus kinase (JAK) 1, JAK 3, and STAT6] and related transcription factor [T cell-specific protein-tyrosine kinase (Lck), extracellular-regulated kinase (ERK)1/2, and nuclear factor-kappaB (NF-kappaB)]. In particular, the imbalance of Th1/Th2 cell differentiation [IL-4, interferon (IFN)-gamma, GATA-binding protein-3 (GATA-3), and T-box expressed in T cells (T-bet)] plays a pivotal role in NO2-induced inflammatory responses. These findings may provide a better understanding of mechanism of NO2-associated respiratory diseases. PMID- 28986737 TI - Assessing the degree of stratification between closely related Holstein-Friesian populations. AB - Genomic information is an important part of the routine evaluation of dairy cattle and provides the wide availability of animals genotyped using single nucleotide polymorphism (SNP) microarrays. We analyzed 2243 Polish and 2294 German Holstein-Friesian bulls genotyped using the Illumina BovineSNP50 BeadChip. For each bull, estimated breeding values (EBVs) calculated from national routine genetic evaluation were available for production traits and for somatic cell score (SCS). Separately for each population, we estimated SNP haplotypes, pairwise linkage disequilibrium (LD), and SNP effects. The SNP genetic covariance between both populations was estimated using a bivariate mixed model. The average LD was lower in the Polish than in the German population and, with increasing genomic distance, LD decays 1.7 times more rapidly in German than in Polish cattle. The comparison of SNP allele frequencies for base populations estimated separately using Polish and German data revealed a very good agreement. The comparison of genetic effects corresponding to various window lengths defined in bp emerged a systematic pattern: regardless of the length of the compared region, few significant differences were found for production traits, while many were observed for SCS. For each trait, the German population had much higher SNP variances than the Polish population and the genetic covariance estimates were all positive. Depending on traits' inheritance mode, the additive genetic variation can be stored in many genes following the infinitesimal model (like for SCS) or distributed between genes with high effects and the polygenic "background" (like for production traits). Accounting for those differences has implications on the prospective international genomic evaluation. PMID- 28986736 TI - Dynamic leaching behavior of geogenic As in soils after cement-based stabilization/solidification. AB - Cement-based stabilization/solidification (S/S) is a practical treatment approach for hazardous waste with anthropogenic As sources; however, its applicability for geogenic As-containing soil and the long-term leaching potential remain uncertain. In this study, semi-dynamic leaching test was performed to investigate the influence of S/S binders (cement blended with fuel ash (FA), furnace bottom ash (FBA), or ground granulated blast furnace slag (GGBS)) on the long-term leaching characteristics of geogenic As. The results showed that mineral admixtures with higher Ca content and pozzolanic activity were more effective in reducing the leached As concentrations. Thus, cement blended with FBA was inferior to other binders in suppressing the As leaching, while 20% replacement of ordinary Portland cement by GGBS was considered most feasible for the S/S treatment of As-containing soils. The leachability of geogenic As was suppressed by the encapsulation effect of solidified matrix and interlocking network of hydration products that were supported by scanning electron microscopy (SEM), X ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS) results. The long-term leaching of geogenic As from the monolithic samples was diffusion controlled. Increasing the Ca content in the samples led to a decrease in diffusion coefficient and an increase in feasibility for "controlled utilization" of the S/S-treated soils. PMID- 28986738 TI - Binding Studies of Isoxsuprine Hydrochloride to Calf Thymus DNA Using Multispectroscopic and Molecular Docking Techniques. AB - In the present work, the interaction of Isoxsuprine (ISX) with Calf thymus DNA (ct-DNA) under physiological conditions (Tris-HCl buffer of pH 7.4) was investigated by using electronic absorption, circular dichroism, viscosity, electrochemical studies, fluorescence techniques, salt effect studies and computational studies. Competitive fluorimetric studies with Hoechst 33258 have shown that ISX exhibit the ability to displace the DNA-bound Hoechst 33258, indicating that it binds to ct-DNA in strong competition with Hoechst 33258 for the minor groove binding. Furthermore, the resulting data showed that ISX cannot displace methylene blue or acridine orange, which are the common intercalator molecules. The viscosity of ct-DNA solution was almost unchanged on addition of ISX and circular dichroism (CD) spectra of ct-DNA showed small changes in the presence of ISX which is in agreement with groove binding mode of interaction. Thus all above studies showed that the ISX drug binds to ct-DNA in a groove binding mode.The salt-effect studies showed the non-electrostatic nature of binding of ISX to ct-DNA. Moreover, molecular docking results support the above experimental data and suggest that ISX prefers to bind on the minor groove of ct DNA. PMID- 28986739 TI - Chronic disease research in Europe and the need for integrated population cohorts. PMID- 28986741 TI - Kruppel-Like Factor 8 Overexpression Correlates with Poor Prognosis in Non-Small Cell Lung Cancer. AB - Kruppel-like factor 8 (KLF8) plays a key role in cancer progression. However, its expression pattern and relationship with clinicopathological characteristics in non-small cell lung cancer (NSCLC) has not been completely elucidated. The study aimed to investigate the expression of KLF8 and its correlation with clinical pathologic features in NSCLC and to explore the potential mechanism. The expression of KLF8 in NSCLC was detected by RT-PCR, Western blot and immunohistochemistry. The expression of Vimentin and E-cadherin, epithelial mesenchymal transition (EMT) markers, were detected by immunohistochemistry in the NSCLC. The relationship between KLF8 expression and various clinicopathological features or EMT markers was investigated. The results showed m-RNA and protein of KLF8 were overexpressed in NSCLC and the percent of KLF8 positive cells was positively correlated with TNM stage, lymph node metastasis and poor overall survive. Moreover, high expression of KLF8 correlated with E cadherin low expression, and Vimentin overexpression. Additionally, COX multivariate regression analysis suggested that TNM stage, KLF8, E-cadherin and Vimentin were independent prognostic indicators for overall survival of patients with NSCLC. The data demonstrate that KLF8 is overexpressed in NSCLC. KLF8 overexpression promotes the malignancy of NSCLC, which mechanism may be involved in EMT. KLF8 maybe serve as a potential therapeutic target for NSCLC. PMID- 28986742 TI - Treatment strategies for central low-grade chondrosarcoma of long bones: a systematic review of the literature and meta-analysis. AB - The need for wide local excision (WLE) versus intralesional (IL) treatment of low grade chondrosarcomas (CS) of the appendicular skeleton remains controversial. We sought to perform a systematic review and meta-analysis to compare different conventional types of surgical treatments for grade I CS in terms of: (1) rate of local recurrence (LR) and metastases, (2) functional outcome as measured by the Musculoskeletal Tumor Society (MSTS) score, (3) complication rate. Eighteen studies enrolling 695 patients met our criteria. Studies reported on WLE versus IL treatment (n = 7), and IL treatment with or without different adjuvants (N = 11). The LR rate was not significantly different between WLE and IL treatment (OR 2.31; 95% CI, 0.85-6.2; P = 0.1). On the contrary, complication rates were significantly lower in favor of IL treatment (OR 2.27; 95% CI, 0.07-0.72; P = 0.012). The mean reported MSTS score ranged from 21.8 to 28.2 for WLE and from 26.5 to 29.7 for IL treatment, with a significant difference in favor of IL treatment. IL treatment as an alternative to WLE does not greatly increase the risk of LR or metastasis and has lower complication rates with better functional scores. In light of the retrospective nature of the studies available, our findings should be interpreted with caution. PMID- 28986740 TI - Integrated Health Care Management of Moderate to Severe TBI in Older Patients-A Narrative Review. AB - PURPOSE OF REVIEW: Traumatic brain injuries are common, especially within the elderly population, which is typically defined as age 65 and older. This narrative review aims at summarizing and critically evaluating important aspects of their health care management in covering the entire pathway from prehospital care to rehabilitation and beyond. RECENT FINDINGS: The number of older patients with traumatic brain injury (TBI) is increasing, and there seem to be differences in all aspects of care along their pathway when compared to younger patients. Despite a higher mortality and a generally less favorable outcome, the current literature shows that older TBI patients have the potential to make significant improvements over time. More research is needed to evaluate the most efficient and integrated clinical pathway from prehospital interventions to rehabilitation as well as the optimal treatment of older TBI patients. Most importantly, they should not be denied access to specific treatments and therapies only based on age. PMID- 28986743 TI - Monosomy 17 in potentially curable HER2-amplified breast cancer: prognostic and predictive impact. AB - PURPOSE: HER2 copy number by fluorescence in situ hybridization (FISH) is typically reported relative to the centromere enumeration probe 17 (CEP17). HER2/CEP17 ratio could be impacted by alterations in the number of chromosome 17 copies. Monosomy of chromosome 17 (m17) is found in ~ 1900 cases of early-stage HER2-positive breast cancer annually in the United States; however, the efficacy of HER2-directed trastuzumab therapy in these patients is not well characterized. Here, we retrospectively identified HER2-amplified, stage I-III breast cancers with m17 and characterized the impact of trastuzumab treatment. METHODS: From January 1, 2000 to June 1, 2011, we identified 99 women with HER2-amplified m17 breast cancers, as defined by a CEP17 signal of < 1.5 per nucleus and a HER2/CEP17 ratio of >= 2.0. RESULTS: Most HER2-amplified m17 patients were treated with trastuzumab plus chemotherapy (51%, n = 50), whereas 31% (n = 31) received chemotherapy alone and 18% (n = 18) received no chemotherapy. The 4-year overall survival (OS) was superior with trastuzumab compared to chemotherapy alone or no chemotherapy (100 vs. 93 vs. 81%, respectively; p = 0.005). OS was not influenced by estrogen/progesterone-receptor (ER/PR) status, tumor stage, or degree of FISH positivity. A proportion of patients who would be considered HER2 negative by standard immunohistochemistry staging criteria (0-1+) were HER2 amplified by FISH. CONCLUSIONS: In the largest series reported to date, patients with HER2-amplified m17 cancers treated with trastuzumab have outcomes comparable to patients from the large phase III adjuvant trastuzumab trials who were HER2 positive, supporting the critical role of HER2-directed therapy in this patient population. PMID- 28986744 TI - Longitudinal Associations between Gender and Ethnic-Racial Identity Felt Pressure from Family and Peers and Self-Esteem among African American and Latino/a Youth. AB - Gender identity felt pressure is negatively associated with adjustment indices, including self-esteem, among children and early adolescents, and both gender and ethnic-racial identity felt pressure are negatively associated with self-esteem among young adults. This study explored the longitudinal associations between gender identity and ethnic-racial identity felt pressure from family and peers to behave in either gender or race/ethnic-accordant ways, and self-esteem among a sample of 750 (49.2% female) African American (n = 194) and Latino/a youth (n = 556) (M = 12.10 years, SD = .97 years). For African Americans, the results revealed significant negative longitudinal associations between (a) ethnic-racial identity felt pressure from family at Time 1 and self-esteem at Time 2 and (b) ethnic-racial identity felt pressure from peers at Time 1 and self-esteem at Time 2, controlling for self-esteem at Time 1. These associations were not found among Latinos/as, nor were associations found between gender identity felt pressure from peers or family and self-esteem. The findings are discussed by drawing on the gender identity and ethnic-racial identity literatures. PMID- 28986745 TI - Nutritional and metabolic stressors on ovine oocyte development and granulosa cell functions in vitro. AB - The present study was undertaken to study the effect of ammonia, urea, non esterified fatty acid (NEFA), and beta-hydroxybutyric acid (beta-OHB) on oocyte development and granulosa cell (GC) growth parameter of ovine (Ovis aries). Ovine oocytes were matured in vitro in the presence of different concentration of ammonia, urea, NEFA, and beta-OHB for 24 h, in vitro inseminated and evaluated for cleavage and blastocyst yield. Same concentrations of ammonia, urea, NEFA, and beta-OHB were examined on growth parameters and hormone secretion activity of granulosa cells in vitro. Real-time reverse transcription polymerase chain reaction was used to evaluate the expression of steroidogenic genes (steroidogenic cytochrome P-450 (CYP11A1, CYP19A1)), cell proliferation-related genes (GDF9, FSHr), and apoptosis-related genes (BCL-2 and BAX). The maturation, cleavage, and blastocyst production rates were significantly lowered in media containing either 200 MUM ammonia or 5 mM urea or high combo NEFA or 1 MUM beta OHB. Exposure of granulosa cell to 400 MUM ammonia or 1 MUM beta-OHB or very high combo or 6 mM urea significantly decreased all the parameters examined compared to lower levels of all nutritional and metabolic stressors. Elevated concentration of metabolic stressors induced GC apoptosis through the BAX/BCL-2 pathway and reduced the steroidogenic gene messenger RNA (mRNA) expression and cell proliferation gene mRNA expression. These results suggested that the decreased function of GCs may cause ovarian dysfunction and offered an improved understanding of the molecular mechanism responsible for the low fertility in metabolic stressed condition. PMID- 28986746 TI - Growth of Cyanobacteria: Optimization for Increased Carbohydrate Content. AB - Growths of Lyngbya limnetica and Oscillatoria obscura were investigated at varying pH, light intensity, temperature, and trace element concentration with a view to optimize these parameters for obtaining the maximum carbohydrate content. The maximum growth for both strains was obtained at pH 9.0 and temperature 20 +/- 3 degrees C using a light intensity of 68.0 MUmol m-2 s-1 with continuous shaking. Growth under the nitrogen starvation condition affected the carbohydrate content more compared to the phosphorus starvation, and maximum concentrations were found as 0.660 and 0.621 g/g of dry biomass for L. limnetica and O. obscura, respectively. Under the optimized nitrogen-rich conditions, the specific growth rates for the two strains were found to be 0.187 and 0.215 day-1, respectively. The two-stage growth studies under nitrogen-rich (stage I) followed by nitrogen starvation (stage II) conditions were performed, and maximum biomass and carbohydrate productivity were found as 0.088 and 0.423 g L-1 day-1 for L. limnetica. This is the first ever attempt to evaluate and optimize various parameters affecting the growth of cyanobacterial biomass of L. limnetica and O. obscura as well as their carbohydrate contents. PMID- 28986747 TI - Saikosaponin a Ameliorates LPS-Induced Acute Lung Injury in Mice. AB - The purpose of this study was to investigate the protective effects of Saikosaponin a (SSa), a triterpene saponin derived from Radix bupleuri, on lipopolysaccharide (LPS)-induced acute lung injury (ALI) using a murine model. The mice were given SSa 1 h after intranasal instillation of LPS. Then, lung histopathological examination, the wet/dry (W/D) ratio, myeloperoxidase (MPO), and inflammatory cytokines in bronchoalveolar lavage fluid (BALF) were detected in this study. The results showed that SSa reduced lung pathological injury induced by LPS. Furthermore, LPS-induced lung W/D ratio, MPO activity, and inflammatory cytokines TNF-alpha and IL-1beta in BALF were significantly inhibited by SSa. In addition, SSa suppressed LPS-induced NF-kappaB activation and NLRP3 inflammasome expression. In conclusion, we found that SSa played a critical anti-inflammatory effect through inhibition of NF-kappaB and NLRP3 signaling pathways and protected against LPS-induced ALI. PMID- 28986748 TI - Anesthetic Isoflurane or Desflurane Plus Surgery Differently Affects Cognitive Function in Alzheimer's Disease Transgenic Mice. AB - Anesthesia/surgery could be associated with cognitive impairment and Alzheimer's disease neuropathogenesis. However, whether surgery under different anesthetics has different effects on cognitive function remains largely unknown. We therefore set out to compare effects of anesthetic isoflurane or desflurane plus surgery on cognitive function and hippocampus levels of synaptic marker (postsynaptic density-95 and synaptophysin) and ATP. Five-month-old AD Transgenic (Tg) (FAD5X) and wild-type male mice received isoflurane or desflurane plus abdominal surgery. We assessed cognitive function in Barnes maze and measured hippocampus levels of postsynaptic density-95, synaptophysin, and ATP in the mice. We determined whether vitamin K2 could mitigate these anesthesia/surgery-induced changes. Isoflurane, but not desflurane, plus surgery increased escape latency and escape distance in Barnes maze probe test and reduced postsynaptic density-95, synaptophysin, and ATP levels as compared to control condition in AD Tg mice. Vitamin K2 attenuated the anesthesia/surgery-induced changes in the AD Tg mice. These findings suggest that isoflurane, but not desflurane, plus surgery might induce cognitive impairment via causing brain energy deficits. Pending confirmative studies in both animals and humans suggest desflurane could be a better choice for AD patients when surgery is needed. Moreover, vitamin K2 could treat cognitive deficiency associated with anesthesia and surgery. PMID- 28986750 TI - Biocidal properties of maltose reduced silver nanoparticles against American foulbrood diseases pathogens. AB - Bee disease caused by spore-forming Paenibacillus larvae and Paenibacillus alvei is a serious problem for honey production. Thus, there is an ongoing effort to find an effective agent that shows broad biocidal activity with minimal environmental hazard. In this study, the biocidal effect of maltose reduced silver nanoparticles (AgNPs) is evaluated against American foulbrood and European foulbrood pathogens. The results demonstrate that the maltose reduced AgNPs are excellent short and long-term biocides against P. larvae isolates. The long-term effect suggests that the Ag+ ions are released from the AgNPs with increasing time in a controlled manner. PMID- 28986749 TI - Pig models on intestinal development and therapeutics. AB - The gastrointestinal tract plays a vital role in nutrient supply, digestion, and absorption, and has a crucial impact on the entire organism. Much attention is being paid to utilize animal models to study the pathogenesis of gastrointestinal diseases in response to intestinal development and health. The piglet has a body size similar to that of the human and is an omnivorous animal with comparable anatomy, nutritional requirements, and digestive and associated inflammatory processes, and displays similarities to the human intestinal microbial ecosystem, which make piglets more appropriate as an animal model for human than other non primate animals. Therefore, the objective of this review is to summarize key attributes of the piglet model with which to study human intestinal development and intestinal health through probing into the etiology of several gastrointestinal diseases, thus providing a theoretical and hopefully practical, basis for further studies on mammalian nutrition, health, and disease, and therapeutics. Given the comparable nutritional requirements and strikingly similar brain developmental patterns between young piglets and humans, the piglet has been used as an important translational model for studying neurodevelopmental outcomes influenced by pediatric nutrition. Because of similarities in anatomy and physiology between pigs and mankind, more emphasises are put on how to use the piglet model for human organ transplantation research. PMID- 28986751 TI - Total Mesenteric Peritonectomy for Peritoneal Metastases (with video). AB - BACKGROUND: Complete cytoreductive surgery (CRS), combining organ resection and peritonectomy, is the only potentially curative treatment for patients with peritoneal metastases (PM).1 , 2 Diffuse mesenteric PM usually represents a contraindication for CRS.3 This report presents a standardized total mesenteric peritonectomy, which provides a therapeutic option of complete CRS for patients with diffuse mesenteric PM. PATIENT: A 73-year-old man had a diagnosis of PM caused by an urachal adenocarcinoma (signet cell type). Initial assessment found a 60-mm urachal tumor above the dome of the urinary bladder. Dedicated magnetic resonance imaging (MRI)4 and explorative laparoscopy confirmed the presence of diffuse mucinous PM suspected of pseudomyxoma peritonei arising from urachus. The patient was treated by a systemic induction chemotherapy including cisplatin, fluorouracil, and docetaxel, with an almost full regression of the PM shown on control MRI. The man then was treated with CRS and hyperthermic intraperitoneal chemotherapy.5 TECHNIQUE: Exploration found persistent diffuse macro-nodular PM with a good response to chemotherapy, a 16/39 peritoneal cancer index,6 and no digestive tract or other organ involvement. The CRS procedure included complete urachus resection, together with appendicectomy, cholecystectomy, omentectomy, and a total parietal and mesenteric peritonectomy, with a completeness of cytoreduction score6 of 1, as illustrated in the video. At this writing, after 6 months of follow-up evaluation, the patient remains free of symptomatic peritoneal disease or local recurrence. CONCLUSION: Total mesenteric peritonectomy can be safely performed with the reported technique irrespective of how widespread PM is along the mesentery as long as few small bowel serous membranes are involved. PMID- 28986752 TI - The Effects of Travel Burden on Outcomes After Resection of Extrahepatic Biliary Malignancies: Results from the US Extrahepatic Biliary Consortium. AB - BACKGROUND: Surgical resection of extrahepatic biliary malignancies has been increasingly centralized at high-volume tertiary care centers. While this has improved outcomes overall, increased travel burden has been associated with worse survival for many other malignancies. We hypothesized that longer travel distances are associated with worse outcomes for these patients as well. STUDY DESIGN: Data was analyzed from the US Extrahepatic Biliary Consortium database, which retrospectively reviewed patients who received resection of extrahepatic biliary malignancies at 10 high-volume centers. Driving distance to the patient's treatment center was measured for 1025 patients. These were divided into four quartiles for analysis: < 24.5, 24.5-57.2, 57.2-117, and < 117 mi. Cox proportional hazard models were then used to measure differences in overall survival. RESULTS: No difference was found between the groups in severity of disease or post-operative complications. The median overall survival in each quartile was as follows: 1st = 1.91, 2nd = 1.60, 3rd = 1.30, and 4th = 1.39 years. Patients in the 3rd and 4th quartile had a significantly lower median household income (p = 0.0001) and a greater proportion Caucasian race (p = 0.0001). However, neither of these was independently associated with overall survival. The two furthest quartiles were found to have decreased overall survival (HR = 1.39, CI = 1.12-1.73 and HR = 1.3, CI = 1.04-1.62), with quartile 3 remaining significant after multivariate analysis (HR = 1.45, CI = 1.04-2.0, p = 0.028). CONCLUSIONS: Longer travel distances were associated with decreased overall survival, especially in the 3rd quartile of our study. Patients traveling longer distances also had a lower household income, suggesting that these patients have significant barriers to care. PMID- 28986754 TI - Uncertainties remain in the status of internal mammary lymph nodes in breast cancers located in lower inner zone. PMID- 28986753 TI - Toward a new and noninvasive diagnostic method of papillary thyroid cancer by using peptide vectorized contrast agents targeted to galectin-1. AB - The incidence of papillary thyroid cancer has increased these last decades due to a better detection. High prevalence of nodules combined with the low incidence of thyroid cancers constitutes an important diagnostic challenge. We propose to develop an alternative diagnostic method to reduce the number of useless and painful thyroidectomies using a vectorized contrast agent for magnetic resonance imaging. Galectin-1 (gal-1), a protein overexpressed in well-differentiated thyroid cancer, has been targeted with a randomized linear 12-mer peptide library using the phage display technique. Selected peptides have been conjugated to ultrasmall superparamagnetic particles of iron oxide (USPIO). Peptides and their corresponding contrast agents have been tested in vitro for their specific binding and toxicity. Two peptides (P1 and P7) were selected according to their affinity toward gal-1. Their binding has been revealed by immunohistochemistry on human thyroid cancer biopsies, and they were co-localized with gal-1 by immunofluorescence on TPC-1 cell line. Both peptides induce a decrease in TPC-1 cells' adhesion to gal-1 immobilized on culture plates. After coupling to USPIO, the peptides preserved their affinity toward gal-1. Their specific binding has been corroborated by co-localization with gal-1 expressed by TPC-1 cells and by their ability to compete with anti-gal-1 antibody. The peptides and their USPIO derivatives produce no toxicity in HepaRG cells as determined by MTT assay. The vectorized contrast agents are potential imaging probes for thyroid cancer diagnosis. Moreover, the two gal-1-targeted peptides prevent cancer cell adhesion by interacting with the carbohydrate-recognition domain of gal-1. PMID- 28986755 TI - Correction to: Hepatocellular Carcinoma with Bone Metastases: Incidence, Prognostic Significance, and Management-Single-Center Experience. AB - The original version of this article unfortunately contained a mistake in the Author group section. Author first names and family names were interchanged. PMID- 28986757 TI - Proposed patient motion monitoring system using feature point tracking with a web camera. AB - Patient motion monitoring systems play an important role in providing accurate treatment dose delivery. We propose a system that utilizes a web camera (frame rate up to 30 fps, maximum resolution of 640 * 480 pixels) and an in-house image processing software (developed using Microsoft Visual C++ and OpenCV). This system is simple to use and convenient to set up. The pyramidal Lucas-Kanade method was applied to calculate motions for each feature point by analysing two consecutive frames. The image processing software employs a color scheme where the defined feature points are blue under stable (no movement) conditions and turn red along with a warning message and an audio signal (beeping alarm) for large patient movements. The initial position of the marker was used by the program to determine the marker positions in all the frames. The software generates a text file that contains the calculated motion for each frame and saves it as a compressed audio video interleave (AVI) file. We proposed a patient motion monitoring system using a web camera, which is simple and convenient to set up, to increase the safety of treatment delivery. PMID- 28986758 TI - The Development of Sociobiology in Relation to Animal Behavior Studies, 1946 1975. AB - This paper aims at bridging a gap between the history of American animal behavior studies and the history of sociobiology. In the post-war period, ecology, comparative psychology and ethology were all investigating animal societies, using different approaches ranging from fieldwork to laboratory studies. We argue that this disunity in "practices of place" (Kohler, Robert E. Landscapes & Labscapes: Exploring the Lab-Field Border in Biology. Chicago: University of Chicago Press, 2002) explains the attempts of dialogue between those three fields and early calls for unity through "sociobiology" by J. Paul Scott. In turn, tensions between the naturalist tradition and the rising reductionist approach in biology provide an original background for a history of Edward Wilson's own version of sociobiology, much beyond the William Hamilton's papers (Journal of Theoretical Biology 7: 1-16, 17-52, 1964) usually considered as its key antecedent. Naturalists were in a defensive position in the geography of the fields studying animal behavior, and in reaction were a driving force behind the various projects of synthesis called "sociobiology". PMID- 28986759 TI - A Road Less Traveled: Spinal Metastasis in Gastric Adenocarcinoma. PMID- 28986760 TI - Willingness of Emerging Adults to Engage in Consensual Non-Monogamy: A Mixed Methods Analysis. AB - Over the past decade, research on consensual non-monogamy (CNM) has increased. However, willingness to engage in CNM is an understudied phenomenon within this field. Because qualitative methods are rarely used to study this phenomenon, little is known about why individuals may or may not be willing to engage in CNM. Further, research on CNM has devoted little attention to the period of emerging adulthood. The current study used a mixed-methods approach to examine a sample of emerging adults' (ages 18-29; N = 549) willingness to engage in CNM. Results from a qualitative content analysis revealed three distinct groups (Unwilling, Willing, and Open-Minded), and several subthemes emerged within each group that help explain why emerging adults are willing to engage in CNM. Quantitative analyses examined the relationship between group membership and demographic characteristics, finding that a greater proportion of women and heterosexual participants were Unwilling. Results also indicated that a greater proportion of men were Willing, and a greater proportion of sexual minorities were Open-Minded. Group mean differences were examined using quantitative measures of CNM attitudes and willingness. The Unwilling group reported more negative attitudes towards CNM compared to the Open-Minded and Willing groups. Additionally, the Open-Minded group reported more negative attitudes compared to the Willing group. On the willingness to engage in CNM Scale, the Unwilling group had lower mean scores compared to the Willing and Open-Minded groups. The Willing group had higher mean scores compared to the Open-Minded group. Implications for CNM research and methodology are discussed. PMID- 28986756 TI - Vascular Dysfunction in Mother and Offspring During Preeclampsia: Contributions from Latin-American Countries. AB - Pregnancy is a physiologically stressful condition that generates a series of functional adaptations by the cardiovascular system. The impact of pregnancy on this system persists from conception beyond birth. Recent evidence suggests that vascular changes associated with pregnancy complications, such as preeclampsia, affect the function of the maternal and offspring vascular systems, after delivery and into adult life. Since the vascular system contributes to systemic homeostasis, defective development or function of blood vessels predisposes both mother and infant to future risk for chronic disease. These alterations in later life range from fertility problems to alterations in the central nervous system or immune system, among others. It is important to note that rates of morbi mortality due to pregnancy complications including preeclampsia, as well as cardiovascular diseases, have a higher incidence in Latin-American countries than in more developed countries. Nonetheless, there is a lack both in the amount and impact of research conducted in Latin America. An impact, although smaller, can be seen when research in vascular disorders related to problems during pregnancy is analyzed. Therefore, in this review, information about preeclampsia and endothelial dysfunction generated from research groups based in Latin-American countries will be highlighted. We relate the need, as present in many other countries in the world, for increased effective regional and international collaboration to generate new data specific to our region on this topic. PMID- 28986761 TI - Detector-based spectral CT with a novel dual-layer technology: principles and applications. AB - Detector-based spectral computed tomography is a novel dual-energy CT technology that employs two layers of detectors to simultaneously collect low- and high energy data in all patients using standard CT protocols. In addition to the conventional polyenergetic images created for each patient, projection-space decomposition is used to generate spectral basis images (photoelectric and Compton scatter) for creating multiple spectral images, including material decomposition (iodine-only, virtual non-contrast, effective atomic number) and virtual monoenergetic images, on-demand according to clinical need. These images are useful in multiple clinical applications, including- improving vascular contrast, improving lesion conspicuity, decreasing artefacts, material characterisation and reducing radiation dose. In this article, we discuss the principles of this novel technology and also illustrate the common clinical applications. Teaching points * The top and bottom layers of dual-layer CT absorb low- and high-energy photons, respectively.* Multiple spectral images are generated by projection-space decomposition.* Spectral images can be generated in all patients scanned in this scanner. PMID- 28986762 TI - Evaluation of the dose and efficacy of ruxolitinib in Japanese patients with myelofibrosis. AB - Ruxolitinib, a potent JAK1/JAK2 inhibitor, improved splenomegaly and myelofibrosis-associated symptoms and prolonged survival compared with placebo and best available therapy in the phase 3 COMFORT studies. Although cytopenias were the most common adverse events associated with ruxolitinib treatment, a COMFORT-I analysis showed that they were managed effectively with dose modifications, without a negative impact on the efficacy of ruxolitinib. Subsequently, studies A2202 and AJP01 showed that ruxolitinib is an effective treatment for Japanese patients with myelofibrosis. We conducted a pooled analysis of these two studies (N = 81) to evaluate the association between ruxolitinib dose and changes in spleen volume or symptoms in Japanese patients. Most patients began treatment at 15 or 20 mg twice daily (BID); 70% received a final titrated dose >= 10 mg BID. Overall, 91% of patients exhibited spleen volume reductions; patients with final titrated doses >= 10 mg BID had larger spleen volume reductions. Similarly, 83% of patients showed improvements in symptom scores; those with a final titrated dose of 20 or 25 mg BID had the greatest reductions. Consistent with COMFORT-I, this pooled analysis indicates that, despite dose adjustments, ruxolitinib provides spleen and symptom control in Japanese patients, with higher doses associated with better responses. PMID- 28986763 TI - Comparison of the trapping effect and antioxidant enzymatic activities using three different light sources in cockchafers. AB - Light traps have been widely used for controlling underground pests. However, very little is known regarding the relationship between trapping effect and antioxidant enzymatic activities using light irradiation in underground pests. Thus, we determined the trapping effect of three light sources of the frequoscillation pest-killing lamp on two species of cockchafers, Serica orientalis Motschulsky (Coleoptera: Melolonthidae) and Anomala corpulenta Motschulsky (Coleoptera: Rutelidae), and evaluated the effect of the same three light sources on the activities of their antioxidant enzymes. The catches of S. orientalis were significantly higher compared to A. corpulenta using light source A in peanut fields in China. After irradiation by light source A, the malondialdehyde (MDA) contents and activities of superoxide dismutase (SOD) and glutathione S-transferases (GST) in S. orientalis were significantly and marginally significantly lower compared to A. corpulenta. Taken together, these results indicated a weaker antioxidant enzyme activity response to light stress and a larger quantity of trapping catches using light irradiation in cockchafers. Thus, we proposed a potential negative relationship between trapping effect and antioxidant enzymatic activities in response to light irradiation in cockchafers. PMID- 28986764 TI - Predictive and prognostic value of 18F-DOPA PET/CT in patients affected by recurrent medullary carcinoma of the thyroid. AB - INTRODUCTION: Medullary thyroid carcinoma (MTC) is a malignancy accounting for about 5-8% of thyroid cancers. Serum calcitonin and carcinoembryonic antigen (CEA) levels are widely used to monitor disease progression. However, prognostic factors able to predict outcomes are highly desirable. We, therefore, aimed to assess the prognostic role of 18F-DOPA PET/CT in patients with recurrent MTC. MATERIALS AND METHODS: 60 patients (mean age 64 +/- 13 years, range 44-82) with recurrent MTC were eligible from a multicenter database. All patients underwent a restaging 18F-DOPA PET/CT, performed at least 6 months after surgery. CEA/calcitonin levels, local recurrences, nodal involvement and metastases at PET/CT were recorded. SUVmax, SUVmean (also normalized to mediastinal uptake) and metabolic tumor volume were automatically calculated for each lesion, by placing a volume of interest around the lesion with 40% of peak activity as threshold for the automatic contouring. The patients were clinically and radiologically followed up for 21 +/- 11 months. Rate of progression-free survival (PFS), disease-specific survival (DSS) and incremental prognostic value of 18F-DOPA PET/CT over conventional imaging modalities were assessed by Kaplan-Meier curves and Log-Rank test. Cox regression univariate and multivariate analyses were performed for assessing predictors of prognosis. RESULTS: 18F-DOPA PET/CT showed abnormal findings in 27 patients (45%) and resulted unremarkable in 33 (55%). PFS was significantly longer in patients with an unremarkable PET/CT scan (p = 0.018). Similarly, an unremarkable PET/CT study was associated with a significantly longer DSS (p = 0.04). 18F-DOPA PET/CT added prognostic value over other imaging modalities both for PFS and for DSS (p < 0.001 and p = 0.012, respectively). Neither semiquantitative PET parameters nor clinical or laboratory data were predictive of a worse PFS and DSS in patients with recurrent MTC. CONCLUSION: 18F-DOPA PET/CT scan has an important prognostic value in predicting disease progression and mortality rate. PMID- 28986765 TI - Addressing challenges in the clinical applications associated with CRISPR/Cas9 technology and ethical questions to prevent its misuse. PMID- 28986766 TI - Comprehensive risk assessment and source identification of selected heavy metals (Cu, Cd, Pb, Zn, Hg, As) in tidal saltmarsh sediments of Shuangtai Estuary, China. AB - Heavy metals do not degrade and can remain in the environment for a long time. In this study, we analyzed the effects of Cu, Cd, Pb, Zn, Hg, and As, on environmental quality, pollutant enrichment, ecological hazard, and source identification of elements in sediments using data collected from samples taken from Shuangtai tidal wetland. The comprehensive pollution indices were used to assess environmental quality; fuzzy similarity analysis and geoaccumulation index were used to analyze pollution accumulation; correlation matrix, principal component analysis, and clustering analysis were used to analyze pollution source; environmental risk index and ecological risk index were used to assess ecological risk. The results showed that the environmental quality was either clean or almost clean. Pollutant enrichment analysis showed that the four sub regions had similar pollution-causing metals to the background values of the soil element of the Liao River Plain, which were ranked according to their similarity. Source identification showed that all the elements were correlated. Ecological hazard analysis showed that the environmental risk index in the study area was less than zero, posing a low ecological risk. Ecological risk of the six elements was as follows: As > Cd > Hg > Cu > Pb > Zn. PMID- 28986768 TI - Scarce Occurrence of Calcification in Human Sinoatrial Nodal Arteries in Old Age. AB - To elucidate age-related changes of the sinoatrial (sinuatrial) nodal (SAN) artery, the authors investigated age-related changes of elements in the SAN artery by direct chemical analysis. In addition, the effects of different arterial origins, arterial sizes, and genders on element accumulation were investigated in the SAN artery. Fifty-nine formalin-fixed adult Thai hearts were dissected, and the following three types of the SAN artery were found: The first type was a single SAN artery arising from the right coronary artery (RCA). The second type was a single SAN artery arising from the proximal segment of the left circumflex artery (LCX). The third type was dual SAN artery arising from both the RCA and the LCX. For element analysis, both 41 single SAN arteries arising from the RCA and the LCX and 18 larger branches of dual SAN artery were used. After the arteries were incinerated with nitric acid and perchloric acid, element contents were determined by inductively coupled plasma-atomic emission spectrometry. It was found that seven element contents such as Ca, P, S, Mg, Zn, Fe, and Na did not change significantly in the SAN arteries with aging. Regarding the relationships among seven elements in the SAN arteries, extremely significant direct correlations were found among P, S, Mg, and Fe contents with one exception. However, no significant correlations were found between Ca and either P or Mg contents in the SAN arteries. To examine an effect of the different arterial origins on element accumulation, the SAN arteries were separated into the RCA and the LCX groups by the arterial origin and age-related changes of element contents were compared between two groups. It was found that there were no significant differences between the RCA and the LCX groups in age-related changes of Ca and P contents. No gender differences were found in age-related changes of Ca and P contents in the SAN arteries. To elucidate whether calcification occurred in the SAN arteries in old age, both the mass ratios of Ca/P and Mg/Ca were estimated in the SAN arteries. The mass ratio of Ca/P increased progressively in the SAN arteries with Ca increase, being not constant. The mass ratio of Mg/Ca decreased gradually in the SAN arteries with Ca increase, but the average mass ratio of Mg/Ca was very high, being 49.4 +/- 16.5%. These results indicated that calcification scarcely occurred in the SAN arteries in old age, independently of the arterial origin and gender. PMID- 28986769 TI - Photocatalytic Activities Enhanced by Au-Plasmonic Nanoparticles on TiO2 Nanotube Photoelectrode Coated with MoO3. AB - Although TiO2 was formerly a common material for photocatalysis reactions, its wide band gap (3.2 eV) results in absorbing only ultraviolet light, which accounts for merely 4% of total sunlight. Modifying TiO2 has become a focus of photocatalysis reaction research, and combining two metal oxide semiconductors is the most common method in the photocatalytic enhancement process. When MoO3 and TiO2 come into contact to form a heterogeneous interface, the photogenerated holes excited from the valence band of MoO3 should be transferred to the valence band of TiO2 to effectively reduce the charge recombination of photogenerated electron-hole pairs. This can efficiently separate the pairs and promote photocatalysis efficiency. In addition, photocurrent enhancement is attributed to the strong near-field and light-scattering effects from plasmonic Ag nanoparticles. In this work, we fabricated MoO3-coated TiO2 nanotube heterostructures with a 3D hierarchical configuration through two-step anodic oxidation and a facile hydrothermal method. This 3D hierarchical structure consists of a TiO2 nanotube core and a MoO3 shell (referred to as TNTs@MoO3), as characterized by field emission scanning electron microscopy and X-ray photoelectron spectroscopy. PMID- 28986771 TI - Degradation of propyl paraben by activated persulfate using iron-containing magnetic carbon xerogels: investigation of water matrix and process synergy effects. AB - An advanced oxidation process comprising an iron-containing magnetic carbon xerogel (CX/Fe) and persulfate was tested for the degradation of propyl paraben (PP), a contaminant of emerging concern, in various water matrices. Moreover, the effect of 20 kHz ultrasound or light irradiation on process performance was evaluated. The pseudo-first order degradation rate of PP was found to increase with increasing SPS concentration (25-500 mg/L) and decreasing PP concentration (1690-420 MUg/L) and solution pH (9-3). Furthermore, the effect of water matrix on kinetics was detrimental depending on the complexity (i.e., wastewater, river water, bottled water) and the concentration of matrix constituents (i.e., humic acid, chloride, bicarbonate). The simultaneous use of CX/Fe and ultrasound as persulfate activators resulted in a synergistic effect, with the level of synergy (between 35 and 50%) depending on the water matrix. Conversely, coupling CX/Fe with simulated solar or UVA irradiation resulted in a cumulative effect in experiments performed in ultrapure water. PMID- 28986772 TI - Laboratory Evolution of Bacillus circulans Xylanase Inserted into Pyrococcus furiosus Maltodextrin-Binding Protein for Increased Xylanase Activity and Thermal Stability Toward Alkaline pH. AB - High xylanase activity and stability toward alkaline pH is strongly desired for pulping and bleaching processes. We previously enhanced thermal stability of Bacillus circulans xylanase (BCX) by inserting into a thermophilic maltodextrin binding protein from Pyrococcus furiosus (PfMBP) (the resulting complex named as PfMBP-BCX165). In the present study, we aimed to evolve the inserted BCX domain within PfMBP-BCX165 for greater xylanase activity toward alkaline pH while maintaining enhanced thermal stability. No BCX sequence variation was required for the thermal stabilization, thus allowing us to explore the entire BCX sequence space for the evolution. Specifically, we randomized the BCX sequence within PfMBP-BCX165 and then screened the resulting libraries to identify a PfMBP BCX165 variant, PfMBP-BCX165T50R. The T50R mutation enhanced xylanase activity of PfMBP-BCX165 toward alkaline pH without compromising thermal stability. When compared to PfMBP-BCX165T50R, the corresponding unfused BCX mutant, BCXT50R, exhibited similar pH dependence of xylanase activity, yet suffered from limited thermal stability. In summary, we showed that one can improve thermal stability and xylanase activity of BCX toward alkaline pH by inserting into PfMBP followed by sequence variation of the BCX domain. Our study also suggested that insertional fusion to PfMBP would be a useful stabilizing platform for evolving many proteins. PMID- 28986773 TI - Feasibility of combined risk stratification with coronary CT angiography and stress myocardial SPECT in patients with chronic coronary artery disease. AB - OBJECTIVE: To examine the additional prognostic value of coronary CT angiography (CTA) over myocardial perfusion imaging (MPI) in patients with suspected or known coronary artery disease. METHODS: A series of 157 patients (mean age 69 +/- 9 years; 76% male; median follow-up 49 months; range 12-82 months) underwent stress MPI with SPECT and coronary CTA within a 6-month interval. Summed stress score (SSS) and summed difference score (SDS) of stress MPI, number of vessels with stenosis, and presence of left main trunk stenosis and high-risk plaques on coronary CTA were examined. Primary endpoints were cardiac death, acute myocardial infarction, or unstable angina requiring revascularization. Secondary endpoints were revascularization > 60 days after the latter imaging test. All patients were followed up for at least 1 year (mean 45 +/- 19 months; range 12-82 months). RESULTS: Nine (6%) patients reached primary endpoints. Cardiac death occurred in 1 (0.6%) patient, myocardial infarction in 5 (3%), and unstable angina requiring hospitalization in 3 (2%). Elective revascularization within 60 days was performed in 31 (20%) patients. Sixteen (10%) patients required revascularization after > 60 days. Primary endpoint event-free survival rates were significantly lower in patients with myocardial ischemia (SDS >= 2) and high risk plaques (HRP), and secondary endpoint event-free survival rates in patients with SSS >= 4 and 3VD. In multivariate analysis, Cox proportional hazards regression analysis revealed HRP (HR = 8.02; P = 0.006) and myocardial ischemia (HR = 11.487; P = 0.025) were significant predictors of primary endpoints, and 3VD of secondary endpoints (HR = 4.981; P = 0.008). Combined ischemia and HRP resulted in the significant increase of the model Chi square in prediction of primary end points from ischemia or HRP alone (17.4 vs. 9.41; P = 0.005, 17.4 vs. 9.39; P = 0.005, respectively). CONCLUSION: Coronary CT angiography may provide additional prognostic information over MPI. PMID- 28986770 TI - Selection history: How reward modulates selectivity of visual attention. AB - Visual attention enables us to selectively prioritize or suppress information in the environment. Prominent models concerned with the control of visual attention differentiate between goal-directed, top-down and stimulus-driven, bottom-up control, with the former determined by current selection goals and the latter determined by physical salience. In the current review, we discuss recent studies that demonstrate that attentional selection does not need to be the result of top down or bottom-up processing but, instead, is often driven by lingering biases due to the "history" of former attention deployments. This review mainly focuses on reward-based history effects; yet other types of history effects such as (intertrial) priming, statistical learning and affective conditioning are also discussed. We argue that evidence from behavioral, eye-movement and neuroimaging studies supports the idea that selection history modulates the topographical landscape of spatial "priority" maps, such that attention is biased toward locations having the highest activation on this map. PMID- 28986774 TI - The history, evolution and basic science of osteotomy techniques. AB - Osteotomy techniques date back to Hippocrates circa 415 BC (Jones Hippocrates collected works I, Harvard University Press, Cambridge, 2006; Brorson in Clin Orthop Relat Res 467(7):1907-1914, 2009). There is debate about the best way to divide the bone surgically and which technique yields the best bone regenerate in lengthening; ensuring predictable new bone formation and healing of the osteotomy are the primary goals. We review the history and techniques of the osteotomy and consider the evidence for optimum bone formation. Methods discussed include variants of the 'drill and osteotome' technique, use of the Gigli saw and use of a power saw. Differences in bone formation through the different techniques are covered. PMID- 28986776 TI - Most of it started with T4 phage and was then taken over. AB - Professor Fumio Arisaka is one of the famous leaders in bacteriophage research, especially in the areas of protein biophysics and structural biology. Autonomous phage morphogenesis is a self-assembly process controlled by subunit-subunit interaction. Under this principle, Fumio has studied T4 tail assembly and morphology. He has also contributed structural information about T4 phage through a combination of X-ray structural analysis and three-dimensional image reconstruction using cryo-electron microscopy. Most of the development of ultracentrifugation applications for molecular assembly and phage morphogenesis research was also performed in Fumio's laboratory. Fumio is a pioneer of supramolecular protein assembly study, and his science continues in the research work of the approximately 150 people who had attended his final lecture at the Tokyo Institute of Technology. PMID- 28986775 TI - Timeline metastatic progression: in the wake of the " seed and soil " theory. AB - Little is known about the natural history of cancer and its evolution to metastasis. Paget was the first to postulate the important role played by microenvironment in metastasis progression. Since, the concept of his "seed and soil" theory has been supported and confirmed. Understanding the chronology and natural course that underlie metastasis is mandatory to deepen this concept and to progress in the development of novel therapeutic strategies. A total of 413 patients who underwent treatment for brain metastasis (2013-2016) were included. The identification of previous and newly diagnosed metastasis was made during the clinical and imaging follow-up. We identified 910 metastases in our series. The 2 , 5-, and 10-year survival estimates were 80% (SD 2), 59.1% (3), and 36% (4), respectively. The median time for first metastasis, referred as metastasis-free survival (MFS) was 15.2 months (SD 1.47). MFS were determined for each metastasis location and were as follows: 7.2 months (SD 8.0) for bone, adrenal 8.4 months (SD 9.4) for adrenal, 13.2 months (SD 1.7) for brain, 14.6 months (SD 5.4) for liver, 25.7 months (SD 11.7) for pleura, 27.7 months (SD 15.9) for peritoneum, 29.8 months (SD 7.2) for spine, 30.2 months (SD 5.2) for lungs, and 54.2 months (SD 12.4) for skin (p < 0.009 log rank). We identified a metastatic timeline process for breast cancer (p < 0.0001 log rank (Mantel-Cox)) and furthermore according to breast subtype cancer (p < 0.0001). We suggest that in addition to Paget's theory, a timeline and a natural history of metastasis exist in patients with cancer. We suppose that some, but not all, primary cancers follow chronological and scheduled metastatic processes to invade organs. PMID- 28986777 TI - Predicting Cardiotoxic Effects of Carbon Monoxide Poisoning Using Speckle Tracking Echocardiography. AB - Carbon monoxide (CO) poisoning could cause significant cardiac injury. This study aimed to evaluate patients with CO poisoning by using speckle tracking echocardiography (STE), a potentially more sensitive technique, to identify left systolic ventricular dysfunction for the first time in the literature. Seventy two patients who were exposed to CO poisoning were studied. Blood collection and echocardiography were performed at admission and after patients' discharge on days 10-15 (mean 12 days). Global longitudinal strain (GLS) and global circumferential strain (GCS) were calculated using STE. In order to find the normal strain levels and to compare it to the patient with CO poisoning, 35 healthy subjects were included in the study. Left ventricular ejection fraction was analyzed according to Simpson's method. Patients were divided into two groups based on their LVEF values. LVEF < 55%, Group 1 (n = 24); LVEF >= 55%, Group 2 (n = 48). The reduction in Group 1 strain levels decreased in correlation with LVEF (p < 0.001) while in Group 2, there were no significant changes in LVEF but strain levels were significantly reduced (p = 0.091; p < 0.001). Compared with the control group patients, admission GLS and GLC values of CO-poisoned patients were significantly low both in Group 1 and 2. On the contrary, no significant difference was observed when compared with follow-up GLS value. For prediction of CO cardiotoxicity, the cutoff value of GLS was >= - 19.1 with a sensitivity of 70.3% and a specificity of 100% [(AUC) 0.840, 95% (CI) 0.735-0.916; p < 0.001] in the ROC curve analyses. GLS was found as independent predictors of cardiotoxicity. Our study demonstrates the potential of using systolic strain values obtained using 2D-STE in determining cardiotoxicity due to CO poisoning. Speckle tracking echocardiography has the potential of demonstrating subtle LV systolic dysfunction even in CO poisoning patients with preserved EF. PMID- 28986778 TI - Students' Learning Experiences from Didactic Teaching Sessions Including Patient Case Examples as Either Text or Video: A Qualitative Study. AB - OBJECTIVES: The aim of this study was to explore medical students' learning experiences from the didactic teaching formats using either text-based patient cases or video-based patient cases with similar content. The authors explored how the two different patient case formats influenced students' perceptions of psychiatric patients and students' reflections on meeting and communicating with psychiatric patients. METHODS: The authors conducted group interviews with 30 medical students who volunteered to participate in interviews and applied inductive thematic content analysis to the transcribed interviews. RESULTS: Students taught with text-based patient cases emphasized excitement and drama towards the personal clinical narratives presented by the teachers during the course, but never referred to the patient cases. Authority and boundary setting were regarded as important in managing patients. Students taught with video-based patient cases, in contrast, often referred to the patient cases when highlighting new insights, including the importance of patient perspectives when communicating with patients. CONCLUSION: The format of patient cases included in teaching may have a substantial impact on students' patient-centeredness. Video-based patient cases are probably more effective than text-based patient cases in fostering patient-centered perspectives in medical students. Teachers sharing stories from their own clinical experiences stimulates both engagement and excitement, but may also provoke unintended stigma and influence an authoritative approach in medical students towards managing patients in clinical psychiatry. PMID- 28986780 TI - RNA Function Prediction. AB - Recent studies have shown that a considerable proportion of eukaryotic genomes are transcribed as noncoding RNA (ncRNA), and regulatory ncRNAs have attracted much attention from researchers in many fields, especially of microRNA (miRNA) and long noncoding RNA (lncRNA). However, most ncRNAs are functionally uncharacterized due to the difficulty to accurately identify their targets. In this chapter, we first summarize the most recent advances in ncRNA research and their primary function. We then discuss the current state-of-the-art computational methods for predicting RNA functions, which comprise three different categories: miRNA function prediction approaches using target genes, lncRNA function prediction based on the guilt-by-association principle, and RNA function prediction approaches based on competing endogenous RNA partners. We consider that the application of these techniques can provide valuable functional and mechanistic insights into ncRNAs, and that they are crucial steps in future functional studies. PMID- 28986779 TI - Predicting RNA Structure with Vfold. AB - In order to carry out biological functions, RNA molecules must fold into specific three-dimensional (3D) structures. Current experimental methods to determine RNA 3D structures are expensive and time consuming. With the recent advances in computational biology, RNA structure prediction is becoming increasingly reliable. This chapter describes a recently developed RNA structure prediction software, Vfold, a virtual bond-based RNA folding model. The main features of Vfold are the physics-based loop free energy calculations for various RNA structure motifs and a template-based assembly method for RNA 3D structure prediction. For illustration, we use the yybP-ykoY Orphan riboswitch as an example to show the implementation of the Vfold model in RNA structure prediction from the sequence. PMID- 28986781 TI - Computational Prediction of Novel miRNAs from Genome-Wide Data. AB - The computational prediction of novel microRNAs (miRNAs) within a full genome involves identifying sequences having the highest chance of being bona fide miRNA precursors (pre-miRNAs). These sequences are usually named candidates to miRNA. The well-known pre-miRNAs are usually only a few in comparison to the hundreds of thousands of potential candidates to miRNA that have to be analyzed. Although the selection of positive labeled examples is straightforward, it is very difficult to build a set of negative examples in order to obtain a good set of training samples for a supervised method. In this chapter we describe an approach to this problem, based on the unsupervised clustering of unlabeled sequences from genome wide data, and the well-known miRNA precursors for the organism under study. Therefore, the protocol developed allows for quick identification of the best candidates to miRNA as those sequences clustered together with known precursors. PMID- 28986782 TI - Protein Structure Modeling with MODELLER. AB - Genome sequencing projects have resulted in a rapid increase in the number of known protein sequences. In contrast, only about one-hundredth of these sequences have been characterized at atomic resolution using experimental structure determination methods. Computational protein structure modeling techniques have the potential to bridge this sequence-structure gap. In the following chapter, we present an example that illustrates the use of MODELLER to construct a comparative model for a protein with unknown structure. Automation of a similar protocol has resulted in models of useful accuracy for domains in more than half of all known protein sequences. PMID- 28986783 TI - Protein Function Prediction. AB - Protein function is a concept that can have different interpretations in different biological contexts, and the number and diversity of novel proteins identified by large-scale "omics" technologies poses increasingly new challenges. In this review we explore current strategies used to predict protein function focused on high-throughput sequence analysis, as for example, inference based on sequence similarity, sequence composition, structure, and protein-protein interaction. Various prediction strategies are discussed together with illustrative workflows highlighting the use of some benchmark tools and knowledge bases in the field. PMID- 28986784 TI - Capturing Three-Dimensional Genome Organization in Individual Cells by Single Cell Hi-C. AB - Hi-C is a powerful method to investigate genome-wide, higher-order chromatin and chromosome conformations averaged from a population of cells. To expand the potential of Hi-C for single-cell analysis, we developed single-cell Hi-C. Similar to the existing "ensemble" Hi-C method, single-cell Hi-C detects proximity-dependent ligation events between cross-linked and restriction-digested chromatin fragments in cells. A major difference between the single-cell Hi-C and ensemble Hi-C protocol is that the proximity-dependent ligation is carried out in the nucleus. This allows the isolation of individual cells in which nearly the entire Hi-C procedure has been carried out, enabling the production of a Hi-C library and data from individual cells. With this new method, we studied genome conformations and found evidence for conserved topological domain organization from cell to cell, but highly variable interdomain contacts and chromosome folding genome wide. In addition, we found that the single-cell Hi-C protocol provided cleaner results with less technical noise suggesting it could be used to improve the ensemble Hi-C technique. PMID- 28986785 TI - Genome-Wide Cell Type-Specific Mapping of In Vivo Chromatin Protein Binding Using an FLP-Inducible DamID System in Drosophila. AB - A thorough study of the genome-wide binding patterns of chromatin proteins is essential for understanding the regulatory mechanisms of genomic processes in eukaryotic nuclei, including DNA replication, transcription, and repair. The DNA adenine methyltransferase identification (DamID) method is a powerful tool to identify genomic binding sites of chromatin proteins. This method does not require fixation of cells and the use of specific antibodies, and has been used to generate genome-wide binding maps of more than a hundred different proteins in Drosophila tissue culture cells. Recent versions of inducible DamID allow performing cell type-specific profiling of chromatin proteins even in small samples of Drosophila tissues that contain heterogeneous cell types. Importantly, with these methods sorting of cells of interest or their nuclei is not necessary as genomic DNA isolated from the whole tissue can be used as an input. Here, I describe in detail an FLP-inducible DamID method, namely generation of suitable transgenic flies, activation of the Dam transgenes by the FLP recombinase, isolation of DNA from small amounts of dissected tissues, and subsequent identification of the DNA binding sites of the chromatin proteins. PMID- 28986786 TI - DNA Methylation Profiling Using Long-Read Single Molecule Real-Time Bisulfite Sequencing (SMRT-BS). AB - For the past two decades, bisulfite sequencing has been a widely used method for quantitative CpG methylation detection of genomic DNA. Coupled with PCR amplicon cloning, bisulfite Sanger sequencing allows for allele-specific CpG methylation assessment; however, its time-consuming protocol and inability to multiplex has recently been overcome by next-generation bisulfite sequencing techniques. Although high-throughput sequencing platforms have enabled greater accuracy in CpG methylation quantitation as a result of increased bisulfite sequencing depth, most common sequencing platforms generate reads that are similar in length to the typical bisulfite PCR size range (~300-500 bp). Using the Pacific Biosciences (PacBio) sequencing platform, we developed single molecule real-time bisulfite sequencing (SMRT-BS), which is an accurate targeted CpG methylation analysis method capable of a high degree of multiplexing and long read lengths. SMRT-BS is reproducible and was found to be concordant with other lower throughput quantitative CpG methylation methods. Moreover, the ability to sequence up to ~1.5-2.0 kb amplicons, when coupled with an optimized bisulfite-conversion protocol, allows for more thorough assessment of CpG islands and increases the capacity for studying the relationship between single nucleotide variants and allele-specific CpG methylation. PMID- 28986787 TI - Copy Number Variation Analysis by Droplet Digital PCR. AB - The health impact of many copy number variants in our genome remains still largely to be discovered. Detecting and genotyping this often complex variation presents a technical challenge. Here we describe a 96-well format droplet digital PCR (ddPCR) protocol for genotyping a common copy variant in the human haptoglobin gene. ddPCR allows for high-throughput and accurate quantitation of gene copy numbers. PMID- 28986788 TI - MicroScale Thermophoresis: A Rapid and Precise Method to Quantify Protein-Nucleic Acid Interactions in Solution. AB - Interactions between nucleic acids and proteins are driving gene expression programs and regulating the development of organisms. The binding affinities of transcription factors to their target sites are essential parameters to reveal their binding site occupancy and function in vivo. Microscale Thermophoresis (MST) is a rapid and precise method allowing for quantitative analysis of molecular interactions in solution on a microliter scale. The technique is based on the movement of molecules in temperature gradients, which is referred to as thermophoresis, and depends on molecule size, charge, and hydration shell. Since at least one of these parameters is typically affected upon binding of a ligand, the method can be used to analyze any kind of biomolecular interaction. This section provides a detailed protocol describing the analysis of DNA-protein interactions, using the transcription factor TTF-I as a model protein that recognizes a 10 bp long sequence motif. PMID- 28986789 TI - Establishment of the CRISPR/Cas9 System for Targeted Gene Disruption and Gene Tagging. AB - CRISPR/Cas9 RNA-guided nucleases refashioned in vivo gene editing approaches for specific gene disruption, gene correction, or gene addition. Moreover, chimeric Cas9 proteins can be applied to direct fused cis-acting effector protein domains, enzymes, or fluorescent markers to DNA to target sequences to regulate gene expression, to introduce epigenetic changes, or to fluorescently label DNA sequences of interest. Here we show how to design guide RNAs for specific DNA targeting. We provide a protocol to customize the CRISPR/Cas9 machinery encoded on commercially available plasmids and present how to test the targeting efficiency of Cas9 with a target-specific gRNA by testing mutation induction efficiency. To exemplify related applications we provide a guideline of how to apply the CRISPR/Cas9 technology for gene labeling. PMID- 28986790 TI - Holistic and Affordable Analyses of MicroRNA Expression Profiles Using Tagged cDNA Libraries and a Multiplex Sequencing Strategy. AB - Small and long noncoding RNAs (ncRNAs) are key regulators of gene expression. Variations in ncRNA expression patterns can consequently affect the control of many cellular processes. Not just since 2006, when Andrew Z Fire and Craig C Mello were jointly awarded The Nobel Prize in Physiology or Medicine for their discovery of RNA interference, great efforts were undertaken to unleash the biomedical applicability of small noncoding RNAs, in particular microRNAs. With the technological evolution of massive parallel sequencing technologies over the last years, which now are available for an increasing number of scientists, there is a demand for comprehensible and efficient workflows reliable even for unique and valuable clinical specimens. Here we describe a highly reproducible low-cost protocol for analyses of miRNA expression patterns using tagged cDNA libraries and a multiplex sequencing strategy following an Illumina-like protocol. This protocol easily allows the identification of expression differences from samples of tissues of 1-2 mm3 and fluids of 50-200 MUL. We further provide entry points into useful computational biology applications, whose target groups explicitly involve non-bioinformaticians. PMID- 28986791 TI - MicroRNA Expression Analysis Using Small RNA Sequencing Discovery and RT-qPCR Based Validation. AB - miRNAs are small noncoding RNA molecules that function as regulators of gene expression. Deregulated miRNA expression has been reported in various diseases including cancer. Due to their small size and high degree of homology, accurate quantification of miRNA expression is technically challenging. In this chapter, we present two different technologies for miRNA quantification: small RNA sequencing and RT-qPCR. PMID- 28986792 TI - Using FirePlexTM Particle Technology for Multiplex MicroRNA Profiling Without RNA Purification. AB - Accuracy of miRNA profiling is enhanced when sample processing can be kept to a minimum, avoiding steps such as RNA purification that can introduce bias and inaccuracies. Here we describe a novel multiplex circulating miRNA assay that enables the profiling of up to 65 miRNAs of choice in the same well directly from plasma (including heparin plasma) or serum, with no need for RNA purification. The main component of the assay is FirePlexTM hydrogel particles, which enable the multiplex capture of miRNAs with picomolar sensitivity and high specificity. Results are obtained using conventional flow cytometry and easy to use software, which allows fast analysis and interpretation of the experimental data. This chapter provides methods to profile miRNAs with PCR sensitivity from as little as 10 MUL of crude biofluid sample, or from less than 100 pg of purified RNA. PMID- 28986793 TI - Multiplex Real-Time PCR Using Encoded Microparticles for MicroRNA Profiling. AB - Multiplex quantitative real-time PCR (qPCR), which measures multiple DNAs in a given sample, has drawn unprecedented attention as a means of verifying the rapidly increasing genetic targets in a single phenotype. We report the detailed procedure of a readily extensible qPCR for multiple microRNA (miRNA) expression analysis using microparticles of primer-immobilized networks as discrete reactors. Individual particles are identified by two-dimensional codes engraved into the particles. It allows high-fidelity signal analysis in the multiplex real time PCR. During the course of PCR, the amplicons accumulate in the volume of the particles with amplification efficiency over 95%. Tens of miRNAs can be quantitatively profiled in a single PCR reaction of this method. PMID- 28986794 TI - Optimized Whole Transcriptome Profiling of Motor Axons. AB - In highly polarized cells such as neurons, most RNA molecules are not randomly distributed but sorted into different compartments. So far, methods to analyze the transcriptome in distinct subcellular compartments are not well established. Here, we first describe the culturing of primary motoneurons in compartmentalized chambers to separate the axons from the somatodendritic compartment. Second, we introduce a method for whole transcriptome amplification followed by high throughput sequencing to analyze the RNA composition of these two different compartments in neuronal cells. PMID- 28986795 TI - 2D-DIGE in Proteomics. AB - The two-dimensional difference gel electrophoresis method is a valuable approach for proteomics. The method, using cyanine fluorescent dyes, allows the co migration of multiple protein samples in the same gel and their simultaneous detection, thus reducing experimental and analytical time. 2D-DIGE, compared to traditional post-staining 2D-PAGE protocols (e.g., colloidal Coomassie or silver nitrate), provides faster and more reliable gel matching, limiting the impact of gel to gel variation, and allows also a good dynamic range for quantitative comparisons. By the use of internal standards, it is possible to normalize for experimental variations in spot intensities and gel patterns. Here we describe the experimental steps we follow in our routine 2D-DIGE procedure that we then apply to multiple biological questions. PMID- 28986796 TI - STAGE-Diging in Proteomics. AB - Proteomics is nowadays a standard tool in life sciences for the analysis of protein abundance, modifications and interactions but has so far failed to enter the clinic for routine applications. New generation mass spectrometers and chromatographic systems are able to cover approximately an entire cell proteome in one run but sample preparation, in terms of time and sample recovery, is still a critical step. Here we describe a modification of the in-gel digestion method, called STAGE-diging, that reduces sample handling, decreases the analysis time and improves protein identification and quantification. This method is particularly useful for those research labs that manage different biological samples and have a limited access to MS instrumentation or are required to perform high-throughput analysis in short time like a clinical laboratory. PMID- 28986797 TI - Protein Arrays I: Antibody Arrays. AB - Antibody arrays represent one of the very early protein array systems where antibodies are used to capture and detect target proteins in a high-throughput platform. The development of high-quality antibodies, nanomaterial-based novel detection probes, as well as innovative imaging technologies and computational tools has tremendously improved the sensitivity, specificity, and robustness of antibody arrays during the past decade. In this protocol we will incorporate the most updated innovations and developments of antibody arrays into the step-by step experimental procedures. This includes antibody printing, sample preparation, array detection, as well as imaging and data analysis. Antibody array could be used for cytokine profiling or mapping of phosphorylation, glycosylation, or other post-translational modifications of target proteins. PMID- 28986798 TI - Protein Arrays II: Antigen Arrays. AB - Antigen arrays are fabricated using various antigens such as DNA, histones, synthetic peptides, recombinant proteins, or cell extracts to detect autoantibodies in autoimmune diseases, alloantibodies in transplantation, drug induced antibodies or cancer-induced antibodies in blood or cell culture supernatant. In this protocol, we will provide a step-by-step executable procedure to perform antigen arrays, including antigen preparation and printing, blocking, sample loading, array detection, imaging, and data analysis. PMID- 28986799 TI - Protein Arrays III: Reverse-Phase Protein Arrays. AB - The reverse-phase protein array (RPPA) is to use highly specific antibodies to interrogate pan or posttranslationally modified protein targets, such as phosphorylated proteins, particularly the proteins involved in cell signaling pathways. In this protocol we will cover the preparation of cell (or tissue) lysates, sample printing, antibody validation, antibody interrogation, signal amplification steps, imaging and data analysis. In this protocol, colorimetric catalyzed signal amplification (CSA) chemistry, fluorescence and near-infrared (NIR) based detection methods will be described. PMID- 28986800 TI - Isolation of Exosomes for the Purpose of Protein Cargo Analysis with the Use of Mass Spectrometry. AB - Exosomes are intercellular messengers with a high potential for diagnostic and therapeutic utility. It is believed that exosomes present in body fluids are responsible for providing signals which inhibit immune cells, interfere with antitumor immunity, and thus influence the response to treatment and its effect. One of the most interesting issues in exosome studies is proper addressing of their cargo composed of nucleic acids and proteins. Effective and selective isolation of extracellular vesicles and identification of proteins present in exosomes has turned out to be a challenging aspect of their exploration. Here we propose a novel approach that is based on isolation of exosomes by mini-size exclusion chromatography which allows efficient, rapid, and reliable isolation of morphologically intact and functionally active exosomes without the need of ultracentrifugation. The purpose of this chapter is to describe a simple and high throughput method to isolate, purify, and identify exosomal proteins using a mass spectrometry approach. The proposed protocol compiles the expertise of two research groups specialized in exosome research and in mass spectrometry-based proteomics. The protocol combines differential centrifugation followed by ultrafiltration, centrifugation-based filtration, and gel filtration on Sepharose 2B in order to obtain exosomal fractions characterized by only low contamination with albumin. PMID- 28986801 TI - Virus-Induced Gene Silencing (VIGS) and Foreign Gene Expression in Pisum sativum L. Using the "One-Step" Bean pod mottle virus (BPMV) Viral Vector. AB - Plant viral vectors have been developed to facilitate gene function studies especially in plant species not amenable to traditional mutational or transgenic modifications. In the Fabaceae plant family, the most widely used viral vector is derived from Bean pod mottle virus (BPMV). Originally developed for overexpression of foreign proteins and VIGS studies in soybean, we adapted the BPMV-derived vector for use in other legume species such as Phaseolus vulgaris and Pisum sativum. Here, we describe a protocol for efficient protein expression and virus-induced gene silencing (VIGS) in Pisum sativum leaves and roots using the "one-step" Bean pod mottle virus (BPMV) viral vector. PMID- 28986802 TI - Re-expressing Epigenetically Silenced Genes by Inducing DNA Demethylation Through Targeting of Ten-Eleven Translocation 2 to Any Given Genomic Locus. AB - Epigenetic editing is a novel methodology to modify the epigenetic landscape of any genomic location. As such, the approach might reprogram expression profiles, without altering the DNA sequence. Epigenetic alterations, including promoter hypermethylation, are associated with an increasing number of human diseases. To exploit this situation, epigenetic editing rises as a new alternative to specifically demethylate abnormally hypermethylated regions. Here, we describe a methodology to actively demethylate the hypermethylated ICAM-1 promoter. Reducing DNA methylation in our target region increased the expression of the ICAM-1 gene. As the ICAM-1 gene in our cell lines was highly methylated (up to 80%), this approach proves a robust manner to reduce methylation for hypermethylated regions. Epigenetic editing therefore not only provides an approach to address mechanisms of gene expression regulation, but also adds to the therapeutic toolbox as current inhibitors of epigenetic enzymes are limited by genome-wide effects. PMID- 28986803 TI - Knockdown of Rice microRNA166 by Short Tandem Target Mimic (STTM). AB - Small RNAs, including microRNAs (miRNAs), are abundant in plants and play key roles in controlling plant development and physiology. miRNAs regulate the expression of the target genes involved in key plant processes. Due to functional redundancy among miRNA family members in plants, an ideal approach to silence the expression of all members simultaneously, for their functional characterization, is desirable. Target mimic (TM) was the first approach to achieve this goal. Short tandem target mimic (STTM) is a potent approach complementing TM for silencing miRNAs in plants. STTMs have been successfully used in dicots to block miRNA functions. Here, we describe in detail the protocol for designing STTM construct to block miRNA functions in rice. Such approach can be applied to silence miRNAs in other monocots as well. PMID- 28986804 TI - RNAi-Mediated Knockdown of Protein Expression. AB - RNA interference is an essential method for studying genomic functions of single genes by loss-of-function experiments. Short interfering siRNAs are efficiently transfected into cultured cells to enable RISC-mediated mRNA cleavage and inhibition of translation in a sequence-specific manner. RNAi enables knockdown of single genes and screening for specific cellular processes or outcomes. In this chapter, we describe a detailed universal protocol for lipoplex-mediated siRNA transfection for cell cultures and cell lysis for subsequent RNA or protein analysis. The experimental procedure is described for verification of knockdown and includes cell lysis for mRNA or protein quantification. Important aspects for specific gene silencing and potential pitfalls are discussed. PMID- 28986805 TI - Engineered Zinc Finger DNA-Binding Domains: Synthesis, Assessment of DNA-Binding Affinity, and Direct Protein Delivery to Mammalian Cells. AB - Zinc finger proteins are the most common among families of DNA-binding transcription factors. Designer transcription factors generated by the fusion of engineered zinc finger DNA-binding domains (ZF-DBDs) to effector domains have been valuable tools for the modulation of gene expression and for targeted genome editing. However, ZF-DBDs without effector domains have also been shown to effectively modulate gene expression by competing with sequence-specific DNA binding transcription factors. Here, we describe the methodology and provide a detailed workflow for the cloning, expression, purification, and direct cell delivery of engineered ZF-DBDs. Using this protocol, ZF-DBDs can be generated with high efficiency in less than 2 weeks. We also describe a nonradioactive method for measuring DNA binding affinity of the purified ZF-DBD proteins as well as a method for direct delivery of the purified ZF-DBDs to mammalian cells. PMID- 28986806 TI - Production, Purification, and Titration of First-Generation Adenovirus Vectors. AB - Vectors based on human adenovirus are highly efficient tools for transient genetic modifications of cells or tissues in vitro and in vivo. They can be utilized for gene addition strategies, knockdown strategies and as transfer vectors for designer nucleases and CRISPR/Cas. They are characterized by high genomic stability and can be produced to high titers. This chapter describes the method how to produce, purify and titrate adenovirus vectors based on human adenovirus type 5. PMID- 28986807 TI - Acupuncture alters pro-inflammatory cytokines in the plasma of maternally separated rat pups. AB - OBJECTIVE: To investigate the potential alleviating effects of acupuncture on maternal separation (MS)-induced changes in plasma pro-inflammatory cytokine levels of rat pups. METHODS: On postnatal day 15, rat pups were randomly assigned to 4 groups (n=6 per group) using a random number table: normal, MS, MS with acupuncture stimulation at Shenmen (HT 7) acupoint (MS+HT 7), and MS with acupuncture stimulation at Chengshan (BL 57) acupoint (MS+BL 57) groups. Rat pups in the normal group were housed with their mothers under standard conditions; those in the MS, MS+HT 7 and MS+BL 57 groups were maternally separated and individually maintained. Acupuncture stimulation was performed at HT 7 or BL 57 acupoints once a day for 7 consecutive days. A tail suspension test was performed to measure immobility time of rats and the plasma was collected on postnatal day 21, then levels of corticosterone (CORT), interleukin (IL)-1beta, IL-6 and glial cell-derived neurotrophic factor (GDNF) in plasma were measured. RESULTS: Compared with the normal group, the immobility time and the plasma levels of CORT, IL-1beta, IL-6 and GDNF in the MS group were significantly increased (P<0.05 or P<0.01). Compared with the MS group, the immobility time and the plasma levels of CORT, IL-1beta, IL-6 and GDNF were significantly reduced in the MS+HT 7 group (P<0.05 or P<0.01). Moreover, the immobility time and plasma levels of IL-1beta and IL-6 in the MS+HT 7 group were significantly lower than those in the MS+BL 57 group (P<0.05). CONCLUSION: Acupuncture stimulation at HT 7 can alleviate the behavioral impairment and changes of the cytokines by MS, indicating that acupuncture can help to relieve MS-induced depression. PMID- 28986809 TI - Review on antioxidants and evaluation procedures. AB - Antioxidants are the substances that are capable of counteracting the damaging effects of the physiological process of oxidation occur in animal tissues. These may be nutrients (vitamins and minerals) as well as enzymes (proteins) in our body that assist in chemical reactions. They are believed to play a role in preventing the development of chronic diseases like cancer, diabetes, heart disease, stroke, Alzheimer's disease, rheumatoid arthritis, and cataracts etc. The present review article emphasizes on the various aspects of oxidants and antioxidants viz. definition, types, causes, mechanism, functions, adverse effects along with various in vivo and in vitro models of evaluation of antioxidant activity of new molecule, compounds or any plant or plant part. This review is one of its kinds which will be of great importance for researchers working in this area in search of antioxidant moieties and their biological evaluation. PMID- 28986808 TI - Contrast-induced nephropathy-time for Western medicine and Chinese medicine to team up. PMID- 28986810 TI - Recent advances in Chinese medicine for contrast-induced nephropathy. PMID- 28986811 TI - Analysis of Herbal Medicine Prescriptions for Patients in An Academic Korean Medical Hospital: A Cross Sectional Study of Electronic Medical Records (2010 2013). AB - OBJECTIVE: To obtain fundamental information for the standardization of herbal medicine in Korea. METHODS: We analyzed the herbal medicine prescription data of patients at the Pusan National University Korean Medicine Hospital from March 2010 to February 2013. We used the Dongui-Bogam (Dong Yi Bao Jian) to classify prescribed herbal medicines. RESULTS: The study revealed that the most frequently prescribed herbal medicine was 'Liuwei Dihuang Pill (LWDHP, )' which was used for invigorating 'Shen (Kidndy)-yin'. 'LWDHP' was most frequently prescribed to male patients aged 50-59, 60-69, 70-79 and 80-89 years, and 'Xionggui Tiaoxue Decoction (XGTXD, )' was most frequently prescribed to female patients aged 30-39 and 40-49 years. According to the International Classification of Diseases (ICD) codes, 'Diseases of the musculoskeletal system and connective tissue' showed the highest prevalence. 'LWDHP' and 'XGTXD' was the most frequently prescribed in categories 5 and 3, respectively. Based on the percentage of prescriptions for each sex, 'Ziyin Jianghuo Decoction ()' was prescribed to mainly male patients, and 'XGTXD' with 'Guima Geban Decoction ()' were prescribed to mainly female patients. CONCLUSION: This study analysis successfully determined the frequency of a variety of herbal medicines, and many restorative herbal medicines were identified and frequently administered. PMID- 28986812 TI - Review of Anemone raddeana Rhizome and its pharmacological effects. AB - The chemical compositions of Anemone raddeana Rhizome, a kind of traditional Chinese medicine, were reviewed, along with its bioactivity and pharmacological properties and method improvements of extracting and detecting triterpenoid saponins. A. raddeana Rhizome is used to treat neuralgia and rheumatism, and is rich in triterpenoid saponins, most of which are pentacyclic, with oleanane as the nucleus. So far, 37 triterpenoid saponins have been determined from the herb. Its reported bioactivity and pharmacological properties have been described as anticancerous, antimicrobial, anti-inflammatory, analgesic, antipyretic, anticonvulsive, antihistaminic, and sedative. It has also been used for the induction of the humoral immune response and treatment of liver fibrosis in chronic hepatitis. However, the herb also has hemolytic effects and can be toxic, which limits its clinical application. Further studies are needed on the pharmaceutical functions, mechanisms, and immunological responses to contribute to the herb's clinical applications. PMID- 28986814 TI - Effect of Shen-Fu Injection () on hemodynamics in early volume resuscitation treated septic shock patients. AB - OBJECTIVE: To investigate the hemodynamic effect of Shen-Fu Injection (, SFI) in early volume resuscitation treated septic shock patients by monitoring pulse indicator continuous cardiac output (PICCO). METHODS: All septic shock patients admitted in the Intensive Care Unit of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from January 1st, 2014 to December 31th, 2015, were reviewed, and totally 65 were enrolled in this study. They were assigned to SFI group (33 cases) and control group (32 cases). All 65 patients underwent conventional treatment mainly including volume resuscitation, antibiotics and vasoactive drugs therapy. The patients of the SFI group received additional 100 mL of SFI intravenously every 12 h. In all 65 patients, the PICCO arterial catheter and vein catheter were implanted within 1 h after the diagnosis of septic shock. In the course of early volume resuscitation, hemodynamic data of patients were recorded by PICCO monitor at 0, 12, and 24 h after the catheter implantation. RESULTS: The hemodynamic indices of the two groups showed no significant differences at the beginning of 0 h (P>0.05). At 12 and 24 h, the hemodynamic indices of SFI group were significantly improved in comparison with the control group (P<0.05), including cardiac index (CI), global end diastolic volume index (GEDI), mean arterial pressure (MAP) and heart rate (HR). In addition, there was no significant change of extra-vascular lung water index between the two groups (P>0.05). CONCLUSION: SFI significantly improved hemodynamic indices such as CI, GEDI, MAP and HR in early volume resuscitation treated septic shock patients. PMID- 28986813 TI - Effect of Jiaotai Pill () on intestinal damage in partially sleep deprived rats. AB - OBJECTIVE: To explore the effect and mechanism of Jiaotai Pill (, JTW) on intestinal mucosal damage in rats with chronic partial sleep deprivation (PSD). METHODS: Obesity resistant (OR) rats were selected, and underwent 4 h PSD by being exposed to environmental noise for 4 weeks. During the whole PSD period, JTW and estazolam were orally given to the rats respectively in the treating groups. Plasma concentration of lipopolysaccharide (LPS) which is the marker of gut-origin endotoxemia was examined. Intestinal morphology changes were observed by optical microscopy. The protein expression of occludin (Ocln) in the intestine was measured by immunofluorescence technique and Western blot. The expressions of circadian proteins cryptochromes (Cry1 and Cry2) in the intestine were also determined. RESULTS: The treatment of JTW significantly decreased LPS level in OR rats with PSD (P<0.05). JTW also attenuated insomnia-induced intestinal injury like shorter, sparse and incomplete villus, wide gap between the villus, mucosal swelling and congesting (P<0.05). These changes were associated with the effect of JTW on up-regulating the expressions of Cry1 protein, Cry2 protein and Ocln protein in the intestine. CONCLUSIONS: JTW has the beneficial effect on improving intestinal mucosal damage caused by PSD. The mechanism appears to be related to the modulation of the expressions of circadian proteins and Ocln protein in the intestine, thereby attenuating inflammation and improving insulin resistance in insomnia rats. PMID- 28986816 TI - Effects of electroacupuncture on metabolic changes in motor cortex and striatum of 6-hydroxydopamine-induced Parkinsonian rats. AB - OBJECTIVE: To explore the possible underlying mechanism by investigating the effect of electroacupuncture (EA) treatment on the primary motor cortex and striatum in a unilateral 6-hydroxydopamine (6-OHDA) induced rat Parkinson's disease (PD) model. METHODS: Male Sprague-Dawley rats were randomly divided into sham group (n=16), model group (n=14), and EA group (n=14). EA stimulation at Dazhui (GV 14) and Baihui (GV20) was applied to PD rats in the EA group for 4 weeks. Behavioral tests were conducted to evaluate the effectiveness of EA treatment. Metabolites were detected by 7.0 T proton nuclear magnetic resonance. RESULTS: Following 4 weeks of EA treatment in PD model rats, the abnormal behavioral impairment induced by 6-OHDA was alleviated. In monitoring changes in metabolic activity, ratios of myoinositol/creatine (Cr) and N-acetyl aspartate (NAA)/Cr in the primary motor cortex were significantly lower at the injected side than the non-injected side in PD rats (P=0.024 and 0.020). The ratios of glutamate + glutamine (Glx)/Cr and NAA/Cr in the striatum were higher and lower, respectively, at the injected side than the non-injected side (P=0.046 and 0.008). EA treatment restored the balance of metabolic activity in the primary motor cortex and striatum. In addition, the taurine/Cr ratio and Glx/Cr ratio were elevated in the striatum of PD model rats compared to sham-lesioned rats (P=0.026 and 0.000). EA treatment alleviated the excessive glutamatergic transmission by down-regulating the striatal Glx/Cr ratio (P=0.001). The Glx/Cr ratio was negatively correlated with floor plane spontaneous locomotion in PD rats (P=0.027 and P=0.0007). CONCLUSIONS: EA treatment is able to normalize the metabolic balance in the primary motor cortex and striatum of PD rats, which may contribute to its therapeutic effect on motor deficits. The striatal Glx/Cr ratio may serve as a potential indicator of PD and a therapeutic target of EA treatment. PMID- 28986817 TI - Isobaric Labeling-Based LC-MS/MS Strategy for Comprehensive Profiling of Human Pancreatic Tissue Proteome. AB - The pancreas is an organ with both endocrine and exocrine functions, and various pathologies, such as pancreatic cancer and diabetes are associated with this organ. Owing to the limited pancreatic biopsy samples available for research, it is critical to make the best use of cadaveric pancreatic tissue for biomarker studies and mechanistic understanding of pancreas-related pathologies. Discovery phase quantitative proteomics has attracted a lot of attention for its capabilities in large-scale protein identification and accurate protein quantification. Here, we describe a workflow using isobaric labeling (tandem mass tag or TMT) based quantitative proteomics to confidently identify and quantify human pancreatic tissue proteome, including sample preparation, isobaric tag labeling, peptide level fractionation, LC-MS/MS, database search, and statistical analysis. PMID- 28986815 TI - Effects of Compound Zhebei Granule () Combined with Doxorubicin on Expression of Specific Surface Antigens in Mice with Transplanted KG-1a Cells. AB - OBJECTIVE: To investigate the effects of Compound Zhebei Granule (, CZG) combined with doxorubicin hydrochloride (adriamycin, ADM) on specific surface antigens in mice with KG-1a transplanted cells. METHODS: A subcutaneous tumor xenograft model was established by injection of the acute myeloid leukemia cell line KG-1a into the axillary flfl anks of BALB/c-nude mice. Twenty-four tumor bearing mice were divided into 4 groups according to a random number table, including normal saline control group, ADM group, high-dose CZG group, and mid-dose CZG group, with 6 mice in each group. Drug administration occurred on the 14th day after cell inoculation, and normal saline control group mice were gavaged with normal saline at 0.2 mL/10 g every other day. ADM group mice were intraperitoneally injected with ADM 1 mg/kg [conversion of adults, 40 mg/(m2*d)] every other day. High- and mid-dose CZG groups mice were gavaged with CZG at the dose of 8 and 4 g/kg respectively every other day and intraperitoneally injected with ADM (1 mg/kg) every other day. The administration period lasted for 10 days. The tumor xenografts were made into mononuclear cell suspensions after dissection, and the expressions of specific surface antigens, including CD34+CD38-, CD34+CD38-CD123+, CD34+CD38-CD96+ and CD34+CD38-CD33+, in KG-1a cell line tumor xenografts were detected by flfl ow cytometry. RESULTS: Compared with the control and ADM groups, expression of CD34+CD38- in the two CZG groups was significantly lower (P<0.05). Compared with the control group, expression of CD34+CD38-CD123+ in the two CZG groups decreased (P<0.05). The high-dose CZG group showed more obvious outcomes compared with the ADM group (P<0.05). Compared with the control and ADM groups, the expression of CD34+CD38-CD96+ and CD34+CD38-CD33+ in the two CZG groups decreased (P<0.05). CONCLUSIONS: CZG combined with doxorubicin could reduce the expression of CD34+CD38-, CD34+CD38-CD123+, CD34+CD38-CD96+ and CD34+CD38-CD33+ in KG-1a cell line tumor xenografts, which shows that CZG could target leukemia stem cells and play a role in chemosensitization. PMID- 28986818 TI - Investigation of spatial resolution improvement by use of a mouth-insert detector in the helmet PET scanner. AB - The dominant factor limiting the intrinsic spatial resolution of a positron emission tomography (PET) system is the size of the crystal elements in the detector. To increase sensitivity and achieve high spatial resolution, it is essential to use advanced depth-of-interaction (DOI) detectors and arrange them close to the subject. The DOI detectors help maintain high spatial resolution by mitigating the parallax error caused by the thickness of the scintillator near the peripheral regions of the field-of-view. As an optimal geometry for a brain PET scanner, with high sensitivity and spatial resolution, we proposed and developed the helmet-chin PET scanner using 54 four-layered DOI detectors consisting of a 16 * 16 * 4 array of GSOZ scintillator crystals with dimensions of 2.8 * 2.8 * 7.5 mm3. All the detectors used in the helmet-chin PET scanner had the same spatial resolution. In this study, we conducted a feasibility study of a new add-on detector arrangement for the helmet PET scanner by replacing the chin detector with a segmented crystal cube, having high spatial resolution in all directions, which can be placed inside the mouth. The crystal cube (which we have named the mouth-insert detector) has an array of 20 * 20 * 20 LYSO crystal segments with dimensions of 1 * 1 * 1 mm3. Thus, the scanner is formed by the combination of the helmet and mouth-insert detectors, and is referred to as the helmet-mouth-insert PET scanner. The results show that the helmet-mouth-insert PET scanner has comparable sensitivity and improved spatial resolution near the center of the hemisphere, compared to the helmet-chin PET scanner. PMID- 28986819 TI - The Surgical Apgar Score Predicts Not Only Short-Term Complications But Also Long Term Prognosis After Esophagectomy. AB - BACKGROUND: The surgical Apgar score (SAS) quantifies three intraoperative factors and predicts postoperative complications, but few reports describe its usefulness in esophagectomy, and no studies to date show its correlation with long-term prognosis after esophagectomy. METHODS: This study investigated 400 cases in which esophagectomy was performed on esophageal malignant tumors at the authors' hospital from January 2007 to January 2017. In this study, SAS was defined as the sum of the scores of three parameters, namely, estimated blood loss, lowest mean arterial pressure, and lowest heart rate, with values extracted from medical records. Postoperative complications classified as Clavien-Dindo grade 3 or higher were also extracted. The study retrospectively compared the relationship of SAS to postoperative complications and survival. RESULTS: Univariate analysis showed that postoperative complications were significantly associated with hypertension (p = 0.017), thoracotomy (p = 0.012), and SAS <= 5 (p < 0.0001), and multivariate analysis showed that hypertension (p = 0.049) and SAS <= 5 (p < 0.0001) were significant predictive factors for complications. In the prognostic analysis, log-rank analysis showed that patients with an SAS <= 5 had a significantly poorer prognosis than those with a SAS > 5 (p = 0.043), especially for complications classified as clinical stage 2 or higher (p = 0.027). In the multivariate analysis, SAS <= 5 was identified as a significantly poor prognostic factor for complications classified as clinical stage 2 or higher (p = 0.029). CONCLUSION: In this study, SAS was useful not only for predicting short-term complications, but also as a long-term prognostic factor after esophagectomy. PMID- 28986820 TI - IgG Fc engineering to modulate antibody effector functions. AB - Therapeutic monoclonal antibodies are among the most effective biotherapeutics to date. An important aspect of antibodies is their ability to bind antigen while at the same time recruit immune effector functions. The majority of approved recombinant monoclonal antibody therapies are of the human IgG1 subclass, which can engage both humoral and cellular components of the immune system. The wealth of information generated about antibodies has afforded investigators the ability to molecularly engineer antibodies to modulate effector functions. Here, we review various antibody engineering efforts intended to improve efficacy and safety relative to the human IgG isotype. Further, we will discuss proposed mechanisms by which engineering approaches led to modified interactions with immune components and provide examples of clinical studies using next generation antibodies. PMID- 28986822 TI - Global Spread of Hemorrhagic Fever Viruses: Predicting Pandemics. AB - As successive epidemics have swept the world, the scientific community has quickly learned from them about the emergence and transmission of communicable diseases. Epidemics usually occur when health systems are unprepared. During an unexpected epidemic, health authorities engage in damage control, fear drives action, and the desire to understand the threat is greatest. As humanity recovers, policy-makers seek scientific expertise to improve their "preparedness" to face future events.Global spread of disease is exemplified by the spread of yellow fever from Africa to the Americas, by the spread of dengue fever through transcontinental migration of mosquitos, by the relentless influenza virus pandemics, and, most recently, by the unexpected emergence of Ebola virus, spread by motorbike and long haul carriers. Other pathogens that are remarkable for their epidemic expansions include the arenavirus hemorrhagic fevers and hantavirus diseases carried by rodents over great geographic distances and the arthropod-borne viruses (West Nile, chikungunya and Zika) enabled by ecology and vector adaptations. Did we learn from the past epidemics? Are we prepared for the worst?The ultimate goal is to develop a resilient global health infrastructure. Besides acquiring treatments, vaccines, and other preventive medicine, bio surveillance is critical to preventing disease emergence and to counteracting its spread. So far, only the western hemisphere has a large and established monitoring system; however, diseases continue to emerge sporadically, in particular in Southeast Asia and South America, illuminating the imperfections of our surveillance. Epidemics destabilize fragile governments, ravage the most vulnerable populations, and threaten the global community.Pandemic risk calculations employ new technologies like computerized maintenance of geographical and historical datasets, Geographic Information Systems (GIS), Next Generation sequencing, and Metagenomics to trace the molecular changes in pathogens during their emergence, and mathematical models to assess risk. Predictions help to pinpoint the hot spots of emergence, the populations at risk, and the pathogens under genetic evolution. Preparedness anticipates the risks, the needs of the population, the capacities of infrastructure, the sources of emergency funding, and finally, the international partnerships needed to manage a disaster before it occurs. At present, the world is in an intermediate phase of trying to reduce health disparities despite exponential population growth, political conflicts, migration, global trade, urbanization, and major environmental changes due to global warming. For the sake of humanity, we must focus on developing the necessary capacities for health surveillance, epidemic preparedness, and pandemic response. PMID- 28986821 TI - Endothelial glycocalyx degradation is more severe in patients with non-pulmonary sepsis compared to pulmonary sepsis and associates with risk of ARDS and other organ dysfunction. AB - BACKGROUND: Disruption of the endothelial glycocalyx contributes to acute lung injury in experimental sepsis but has not been well studied in humans. To study glycocalyx degradation in sepsis-induced ARDS, we measured plasma levels of syndecan-1, a marker for glycocalyx degradation. METHODS: The present study is a retrospective observational study of 262 ventilated medical ICU patients at risk of ARDS due to severe sepsis and APACHE II >= 25. Plasma syndecan-1 was measured at study enrollment. Primary analysis focused on the association between syndecan 1 levels and the development of ARDS, other organ dysfunction (Brussels criteria), or in-hospital mortality. RESULTS: Overall, 135 (52%) patients developed ARDS. In patients with non-pulmonary sepsis, syndecan-1 levels were associated with ARDS (p = 0.05). Regardless of etiology of sepsis, higher syndecan-1 levels were associated with hepatic (p < 0.001), renal (p = 0.003), coagulation (p = 0.001), and circulatory (p = 0.02) failure as well as in hospital mortality (p = 0.001), and there was a significant association between syndecan-1 levels and the number of vasopressors required in the first 24 h (p < 0.001). In addition, elevated syndecan levels were independently predictive of mortality in multivariable logistic regression adjusted for age and APACHE II score (odds ratio 1.85 per log increase in syndecan-1, 95% CI 1.056-3.241, p = 0.03). CONCLUSION: The extent of endothelial glycocalyx degradation is associated with non-pulmonary organ dysfunction in subjects with sepsis and is associated with ARDS but only in the subgroup with non-pulmonary sepsis. Measurement of syndecan-1 levels in sepsis patients might be useful for identifying patients at high risk of organ dysfunction and mortality as well as those who could benefit from therapies targeted at protecting or restoring the glycocalyx. PMID- 28986823 TI - An Approach to the Identification and Phylogenetic Analysis of Emerging and Hemorrhagic Fever Viruses. AB - An important aspect of virological surveillance is the identification of the detected viruses. Broad surveillance, that typically employs deep sequencing of collected tissue samples, provides the investigator with many sequence files constructed from overlapping stretches of DNA sequences. Directed surveillance for viruses of a specific taxonomic group provides the investigator with sequence files from cDNA amplified using specific primers to conserved viral regions. Here we will describe general approaches to identify hemorrhagic viral agents through phylogenetic analysis of cDNA sequences obtained during surveillance activities. PMID- 28986824 TI - Preliminary Classification of Novel Hemorrhagic Fever-Causing Viruses Using Sequence-Based PAirwise Sequence Comparison (PASC) Analysis. AB - During the last decade, genome sequence-based classification of viruses has become increasingly prominent. Viruses can be even classified based on coding complete genome sequence data alone. Nevertheless, classification remains arduous as experts are required to establish phylogenetic trees to depict the evolutionary relationships of such sequences for preliminary taxonomic placement. Pairwise sequence comparison (PASC) of genomes is one of several novel methods for establishing relationships among viruses. This method, provided by the US National Center for Biotechnology Information as an open-access tool, circumvents phylogenetics, and yet PASC results are often in agreement with those of phylogenetic analyses. Computationally inexpensive, PASC can be easily performed by non-taxonomists. Here we describe how to use the PASC tool for the preliminary classification of novel viral hemorrhagic fever-causing viruses. PMID- 28986825 TI - Epidemiological Surveillance of Viral Hemorrhagic Fevers With Emphasis on Clinical Virology. AB - This article will outline surveillance approaches for viral hemorrhagic fevers. Specific methods for surveillance of clinical samples will be emphasized. Separate articles will describe methods for surveillance of rodent-borne viruses (roboviruses) and arthropod-borne viruses (arboviruses). Since the appearance of hantaviruses and arenaviruses in the Americas, more than 30 different species in each group have been established, and therefore they have become the most frequently emerging viruses. Flaviviruses such as yellow fever and dengue viruses, although easier to recognize, are also more widely spread and therefore considered a very important public health issue, particularly for under-developed countries. On the other hand, marburgviruses and ebolaviruses, previously thought to be restricted to the African continent, have recently been shown to be more global. For many of these agents virus isolation has been a challenging task: trapping the specific vectors (mosquitoes and ticks), and reservoirs (rodents and bats), or obtaining the samples from suspected clinical human cases demands special protective gear, uncommon devices (respirators), special facilities (BSL 3 and 4), and particular skills to recognize the slow and inapparent cytopathic effects in cell culture. Alternatively, serological and molecular approaches have been very helpful in discovering and describing newly emerging viruses in many areas where the previous resources are unavailable. Unfortunately, in many cases, detailed studies have been performed only after outbreaks occur, and then active surveillance is needed to prevent viral dissemination in human populations. PMID- 28986826 TI - Diagnostics for Lassa Fever: Detecting Host Antibody Responses. AB - There are two types of viral diagnostics: (1) those that detect components of the pathogen (like viral RNA or proteins) and (2) those that detect host molecules that rise or fall as a consequence of pathogen infection (like anti-viral antibodies or virus-induced inflammatory cytokines). Quantitative PCR to detect Lassa RNA, and clinical chemistry to detect high liver enzymes (AST/ALT) are commonly used to diagnose Lassa fever. Here, we discuss the various types of diagnostics for Lassa fever and the urgent need for early diagnosis. We also describe a protocol for using the attenuated Lassa vaccine candidate, ML29 , as an antigen for detecting Lassa-specific antibodies. Since antibodies are developed late in the progression of Lassa fever disease, this is not an early diagnostic, but is more useful in surveillance of the population to determine the sero-prevalence of antibodies to Lassa virus (LASV ), and to define treatment options for people in close contact with a Lassa-infected person. PMID- 28986827 TI - Sampling Design and Mosquito Trapping for Surveillance of Arboviral Activity. AB - Mosquitoes are the most important vectors for arboviral human diseases across the world. Diseases such as Dengue Fever (DF), West Nile Virus (WNV), Yellow Fever (YF), Japanese Encephalitis (JE), Venezuelan Equine Encephalitis (VEE), and St. Louis Encephalitis (SLE), among others, have a deep impact in public health. Usually mosquitoes acquire the arboviral infection when they feed on viremic animals (birds or mammals), so their infection can be detected along the year or in short periods of time (seasons). All of this depends on the frequency and seasonality of the encounters between viremic animals and vectors.With the convergence of several phenomena like the increasing traveling of human populations, globalization of economy and more recently the global warming, the introduction of nonendemic arbovirus into new areas has become the current scenario. As examples of this new social and environmental frame we can mention the outbreak of West Nile Virus in North America in the late 1990s and more recently the outbreaks of chikungunya and Zika virus in the Americas. The present chapter deals with one of the first steps in the development of research studies and diagnosis programs, the surveillance of arboviruses in their vectors, the sampling design and mosquito trapping methods. The chapter also includes some important considerations and tips to be taken into account during the mosquito fieldwork. PMID- 28986828 TI - Epidemiological Surveillance of Rodent-Borne Viruses (Roboviruses). AB - This article will outline surveillance approaches for rodent-borne viruses (roboviruses). We present a synopsis of the main categories of trapping methods with some notes about their use in fieldwork. We also describe the types of laboratory analysis commonly used in Robovirus surveillance. PMID- 28986829 TI - Entry Studies of New World Arenaviruses. AB - Identification of cell moieties involved in viral binding and internalization is essential since their expression would render a cell susceptible. Further steps that allow the uncoating of the viral particle at the right subcellular localization have been intensively studied. These "entry" steps could determine cell permissiveness and often define tissue and host tropism. Therefore applying the right and, when possible, straightforward experimental approaches would shorten avenues to the complete knowledge of this first and key step of any viral life cycle. Mammarenaviruses are enveloped viruses that enter the host cell via receptor-mediated endocytosis. In this chapter we present a set of customized experimental approaches and tools that were used to describe the entry of Junin virus (JUNV), and other New World mammarenavirus members, into mammalian cells. PMID- 28986830 TI - Studies of Lassa Virus Cell Entry. AB - Host cell entry is the first and most fundamental step of every virus infection and represents a major barrier for zoonotic transmission and viral emergence. Targeting viral entry appears further as a promising strategy for therapeutic intervention. Several cellular receptors have been identified for Lassa virus, including dystroglycan, TAM receptor tyrosine kinases, and C-type lectins. Upon receptor binding, LASV enters the host cell via a largely unknown clathrin- and dynamin-independent endocytotic pathway that delivers the virus to late endosomes, where fusion occurs after engagement of a second, intracellular receptor, the late endosomal/lysosomal resident protein LAMP1. Here, we describe a series of experimental approaches to investigate LASV cell entry and to test candidate inhibitors for their action at this early and decisive step of infection. PMID- 28986831 TI - A Cell-Cell Fusion Assay to Assess Arenavirus Envelope Glycoprotein Membrane Fusion Activity. AB - For many viruses that enter their target cells through pH-dependent fusion of the viral and endosomal membranes, cell-cell fusion assays can provide an experimental platform for investigating the structure-function relationships that promote envelope glycoprotein membrane-fusion activity. Typically, these assays employ effector cells expressing the recombinant envelope glycoprotein on the cell surface and target cells engineered to quantitatively report fusion with the effector cell. In the protocol described here, Vero cells are transfected with a plasmid encoding the arenavirus envelope glycoprotein complex GPC and infected with the vTF7-3 vaccinia virus expressing the bacteriophage T7 RNA polymerase. These effector cells are mixed with target cells infected with the vCB21R-lacZ vaccinia virus encoding a beta-galactosidase reporter under the control of the T7 promoter. Cell-cell fusion is induced upon exposure to low-pH medium (pH 5.0), and the resultant expression of the beta-galactosidase reporter is quantitated using a chemiluminescent substrate. We have utilized this robust microplate cell cell fusion assay extensively to study arenavirus entry and its inhibition by small-molecule fusion inhibitors. PMID- 28986832 TI - Assays to Assess Arenaviral Glycoprotein Function. AB - Arenaviruses, such as Lassa virus (LASV) and Pichinde virus (PICV), are enveloped viruses with a bi-segmented ambisense RNA genome. The large (L) genomic segment encodes the Z matrix protein and the L RNA-dependent RNA polymerase, whereas the small (S) genomic segment encodes the nucleoprotein (NP) and the glycoprotein precursor complex (GPC). GPC is processed by signal peptidase in the endoplasmic reticulum into the stable signal peptide (SSP) and GP1/GP2, which is further cleaved by the Golgi-resident subtilisin kexin isozyme-1 (SKI-1)/site-1 protease (S1P) into the cellular receptor-recognition subunit GP1 and the transmembrane subunit GP2, which helps promote the membrane fusion reaction to allow virus entry into the cell. This article describes assays to assess PICV GPC expression, proteolytic processing, fusion function, and GPC-mediated virus-like particle (VLP) entry into cells under tissue-culture conditions. PMID- 28986833 TI - Expression and X-Ray Structural Determination of the Nucleoprotein of Lassa Fever Virus. AB - We describe methods to express the nucleoprotein (NP) of Lassa fever virus (LASV) in E. coli, to purify and crystallize it using the sitting-drop vapor diffusion method. The crystals were screened using Rigaku micro-007 X-ray generator and a dataset was collected at a resolution of 2.36 A. The crystals belong to space group P3, with the unit cell parameters a = b = 176.35 A, c = 56.40 A, alpha = beta = 90 degrees , and gamma = 120 degrees . Using the X-ray diffraction method, we constructed a three-dimensional structure of the LASV NP that should aid in the development of novel therapeutic strategies against this virus, for which vaccine and effective treatment modalities are currently unavailable. PMID- 28986834 TI - Assays to Demonstrate the Roles of Arenaviral Nucleoproteins (NPs) in Viral RNA Synthesis and in Suppressing Type I Interferon. AB - Arenaviruses, such as Lassa virus (LASV) and Pichinde virus (PICV), are enveloped viruses with a bi-segmented ambisense RNA genome. The large (L) genomic segment encodes the Z matrix protein and the L RNA-dependent RNA polymerase, whereas the small (S) genomic segment encodes the nucleoprotein (NP) and the glycoprotein (GPC). The NP encapsidates viral genome, is required for viral transcription and replication, and acts as a type I interferon (IFN) antagonist. This article describes assays to demonstrate that NP contains 3'-5' exoribonuclease (RNase) activity to degrade modeled RNA of the pathogen-associated molecular pattern type and suppresses the IFNbeta promoter-driven luciferase reporter gene. The minigenomic (MG) assay is used to assess the role of NP in replicating and transcribing a viral promoter-driven luciferase reporter gene. These powerful assays demonstrate the versatility of NP in mediating viral replication as well as in modulating host innate immune responses. PMID- 28986835 TI - Intracellular Detection of Viral Transcription and Replication Using RNA FISH. AB - Many hemorrhagic fever viruses require BSL-3 or BSL-4 laboratory containment for study. The necessary safety precautions associated with this work often contribute to longer assay times and lengthy decontamination procedures. Here we will discuss recent advances in RNA fluorescence in situ hybridization (FISH) that not only allow entirely new investigations into the replication of these viruses but also demonstrate how this method can be applied to any virus with a known sequence and how it can be rapidly performed to minimize time spent in high containment. We have adapted existing protocols for mRNA detection with appropriate changes for examining viruses in a variety of containment laboratories (Shaffer et al., PLoS One 8:e75120, 2013; Raj et al., Nat Methods 5:877-879, 2008). PMID- 28986836 TI - Hemorrhagic Fever Virus Budding Studies. AB - Independent expression of the VP40 or Z matrix proteins of filoviruses (marburgviruses and ebolaviruses) and arenaviruses (Lassa fever and Junin), respectively, gives rise to the production and release of virus-like particles (VLPs) that are morphologically identical to infectious virions. We can detect and quantify VLP production and egress in mammalian cells by transient transfection, SDS-PAGE, Western blotting, and live cell imaging techniques such as total internal reflection fluorescence (TIRF) microscopy. Since the VLP budding assay accurately mimics budding of infectious virus, this BSL-2 assay is safe and useful for the interrogation of both viral and host determinants required for budding and can be used as an initial screen to identify and validate small molecule inhibitors of virus release and spread. PMID- 28986837 TI - Roles of Arenavirus Z Protein in Mediating Virion Budding, Viral Transcription Inhibition and Interferon-Beta Suppression. AB - The smallest arenaviral protein is the zinc-finger protein (Z) that belongs to the RING finger protein family. Z serves as a main component required for virus budding from the membrane of the infected cells through self-oligomerization, a process that can be aided by the viral nucleoprotein (NP) to form the viral matrix of progeny virus particles. Z has also been shown to be essential for mediating viral transcriptional repression activity by locking the L polymerase onto the viral promoter in a catalytically inactive state, thus limiting viral replication. The Z protein has also recently been shown to inhibit the type I interferon-induction pathway by directly binding to the intracellular pathogen sensor proteins RIG-I and MDA5, and thus inhibiting their normal functions. This chapter describes several assays used to examine the important roles of the arenaviral Z protein in mediating virus budding (i.e., either Z self-budding or NP-Z budding activities), viral transcriptional inhibition in a viral minigenome (MG) assay, and type I IFN suppression in an IFN-beta promoter-mediated luciferase reporter assay. PMID- 28986838 TI - Structure-Function Assays for Crimean-Congo Hemorrhagic Fever Virus Polymerase. AB - The recently developed Crimean-Congo hemorrhagic fever virus (CCHFV) reverse genetics systems have paved the way for experiments looking to identify and characterize the roles played by viral and cellular proteins in the CCHFV life cycle. In particular, the development of the noninfectious minigenome and virus like particle (VLP) systems is a tremendous technological advance, as these systems allow for precisely targeting proteins or nucleic acids and measuring the effects these mutations or treatments have on viral life cycle stages. Importantly, these systems can be used at low-containment levels. Presented are the materials and methods currently available to study CCHFV transcription, replication, and translation in the context of a minigenome or VLP. PMID- 28986839 TI - Minigenome Systems for Filoviruses. AB - Filoviruses are among the most pathogenic viruses known to man, and work with live viruses is restricted to maximum containment laboratories. In order to study individual aspects of the virus life cycle outside of maximum containment laboratories, life cycle modeling systems have been established, which use reporter-encoding miniature versions of the viral genome called minigenomes. With basic minigenome systems viral genome replication and transcription can be studied, whereas more advanced systems also allow us to model other aspects of the virus life cycle outside of a maximum containment laboratory. These systems, therefore, represent powerful tools to study the biology of filoviruses, and for the screening and development of antivirals. PMID- 28986841 TI - Murine Models for Viral Hemorrhagic Fever. AB - Hemorrhagic fever (HF) viruses, such as Lassa, Ebola, and dengue viruses, represent major human health risks due to their highly contagious nature, the severity of the clinical manifestations induced, the lack of vaccines, and the very limited therapeutic options currently available. Appropriate animal models are obviously critical to study disease pathogenesis and develop efficient therapies. We recently reported that the clone 13 (Cl13) variant of the lymphocytic choriomeningitis virus (LCMV-Cl13), a prototype arenavirus closely related to Lassa virus, causes in some mouse strains endothelial damage, vascular leakage, platelet loss, and death, mimicking pathological aspects typically observed in Lassa and other HF syndromes. This model has the advantage that the mice used are fully immunocompetent, allowing studies on the contribution of the immune response to disease progression. Moreover, LCMV is very well characterized and exhibits limited pathogenicity in humans, allowing handling in convenient BSL 2 facilities. In this chapter we outline protocols for the induction and analysis of arenavirus-mediated pathogenesis in the NZB/LCMV model, including mouse infection, virus titer determination, platelet counting, phenotypic analysis of virus-specific T cells, and assessment of vascular permeability. PMID- 28986840 TI - Establishment of Bisegmented and Trisegmented Reverse Genetics Systems to Generate Recombinant Pichinde Viruses. AB - Pichinde virus (PICV), isolated from rice rats in Colombia, South America, is an enveloped arenavirus with a bisegmented RNA genome. The large (L) genomic segment encodes the Z matrix protein and the L RNA-dependent RNA polymerase, whereas the small (S) genomic segment encodes the nucleoprotein (NP) and the glycoprotein (GPC). This article describes the successful development of reverse genetics systems to generate recombinant PICV with either a bisegmented or trisegmented genome. We have successfully demonstrated that these systems can generate high titered and genetically stable replication-competent viruses from plasmid transfection into appropriate cell lines. These systems demonstrate the power and versatility of reverse genetic technology to generate recombinant arenaviruses for use in pathogenesis studies and as new viral vaccine vectors. PMID- 28986842 TI - Testing Experimental Therapies in a Guinea Pig Model for Hemorrhagic Fever. AB - Hemorrhagic fever viruses are among the deadliest pathogens known to humans, and often, licensed medical countermeasures are unavailable to prevent or treat infections. Guinea pigs are a commonly used animal for the preclinical development of any experimental candidates, typically to confirm data generated in mice and as a way to validate and support further testing in nonhuman primates. In this chapter, we use Sudan virus (SUDV), a lethal filovirus closely related to Ebola virus, as an example of the steps required for generating a guinea pig-adapted isolate that is used to test a monoclonal antibody-based therapy against viral hemorrhagic fevers. PMID- 28986843 TI - A Primate Model for Viral Hemorrhagic Fever. AB - Lymphocytic choriomeningitis virus strain WE (LCMV-WE), a Risk Group 3 virus, causes a disease in rhesus monkeys that closely resembles human infection with Lassa fever virus, a Risk Group 4 agent. Three stages of disease progression have been defined and profiled in this model: pre-viremic, viremic, and terminal. The earliest or pre-viremic stage reveals changes in the blood profile predictive of the later stages of disease. In order to identify whether specific changes are pathognomonic, it was necessary to perform a parallel infection with an attenuated virus (LCMV-Armstrong). Here we review the use of nonhuman primates to model viral hemorrhagic fever and offer a step-by-step guide to using a rhesus macaque model for Lassa fever. PMID- 28986844 TI - A Primary Human Liver Cell Culture Model for Hemorrhagic Fever Viruses. AB - Viral hemorrhagic fevers affect liver functions such as important metabolic processes and the replacement of new blood cells, coagulation factors, and growth factors. Typically, multi-organ diseases such as viral hemorrhagic fevers are studied in an organism, but it is also possible to derive information about the molecular events involved in disease processes by focusing on liver cell culture. Here we describe a multi-cell culture system that is capable of replicating the arenavirus LCMV-WE, a virus that can cause hemorrhagic fever in primates, as a model for liver infection by a hemorrhagic fever virus. PMID- 28986845 TI - Protocol for the Production of a Vaccine Against Argentinian Hemorrhagic Fever. AB - Argentinian hemorrhagic Fever (AHF) is a febrile, acute disease caused by Junin virus (JUNV), a member of the Arenaviridae. Different approaches to obtain an effective antigen to prevent AHF using complete live or inactivated virus, as well as molecular constructs, have reached diverse development stages. This chapter refers to JUNV live attenuated vaccine strain Candid #1, currently used in Argentina to prevent AHF. A general standardized protocol used at Instituto Nacional de Enfermedades Virales Humanas (Pergamino, Pcia. Buenos Aires, Argentina) to manufacture the tissue culture derived Candid #1 vaccine is described. Intermediate stages like viral seeds and cell culture bank management, bulk vaccine manufacture, and finished product processing are also separately presented in terms of Production and Quality Control/Quality Assurance requirements, under the Adminitracion Nacional de Medicamentos, Alimentos y Tecnologia Medica (ANMAT), the Argentine national regulatory authority. PMID- 28986846 TI - Detection of Virus-Antibody Immune Complexes in Secondary Dengue Virus Infection. AB - It has been reported that virus-antibody immune complexes formed during secondary dengue virus infection are associated with increased disease severity. Here, we describe the details of a plaque titration method that uses FcgammaR -expressing BHK cells to detect and quantify infectious virus-immune complexes and a quantitative real-time PCR method for the quantification of virus genome in patients with secondary dengue infection. These methods detect both viruses in free-form and in immune complexes in patients with dengue infection, and are useful for determining viremia levels and patterns that better reflect in vivo conditions. PMID- 28986847 TI - Future Approaches to DNA Vaccination Against Hemorrhagic Fever Viruses. AB - To date, there is no protective vaccine for Ebola virus infection. Safety concerns have prevented the use of live-attenuated vaccines, and forced researchers to examine new vaccine formulations. DNA vaccination is an attractive method for inducing protective immunity to a variety of pathogens, but the low immunogenicity seen in larger animals and humans has hindered its usage. Various approaches have been used to improve the immunogenicity of DNA vaccines, but the most successful, and widespread, is electroporation. Of increasing interest is the use of molecular adjuvants to produce immunomodulatory signals that can both amplify and direct the immune response. When combined, these approaches have the possibility to push DNA vaccination into the forefront of medicine. PMID- 28986848 TI - Identifying Restriction Factors for Hemorrhagic Fever Viruses: Dengue and Junin. AB - Host restriction factors are cellular components that interfere with viral multiplication. They are up-regulated and expressed upon viral infection and in consequence their activity is specific. So far several important restriction factors have been described against diverse viruses. The cellular antiviral mechanisms defined include proteins with the ability to interfere with early steps of viral replication and others that have been shown to block viral morphogenesis. However, other strategies by which the antiviral action is exerted still remain elusive. An additional interesting matter is how viruses also developed ways to by-pass these host-specific obstacles. Thus, unusual cell localization or re-localization represents a frequent virus choice to evade the cellular surveillance. In the present chapter, we summarize methods to identify cell restriction factors, their antiviral activity, and possible subcellular locations where their activity can take place. PMID- 28986849 TI - Determining the Virus Life-Cycle Stage Blocked by an Antiviral. AB - Among the members of the Arenaviridae family, Junin virus and Lassa virus represent important human health threats generating annual outbreaks of severe human hemorrhagic fever (HF) in endemic areas of Argentina and Western Africa, respectively. Given the lack of a specific and safe chemotherapy, the search for effective antiviral compounds is a continuous demanding effort. During the last two decades, academic research studies originated important results identifying novel molecules to be considered for further in vivo characterization. This chapter summarizes experimental in vitro approaches used to determine the possible mechanism of action of these antiviral agents. PMID- 28986850 TI - Retrovirus-Based Surrogate Systems for BSL-2 High-Throughput Screening of Antivirals Targeting BSL-3/4 Hemorrhagic Fever-Causing Viruses. AB - The majority of viruses causing hemorrhagic fever in humans are Risk Group 3 or 4 pathogens and, therefore, can only be handled in biosafety level 3 or 4 (BSL-3/4) containment laboratories. The restricted number of such laboratories, the substantial financial requirements to maintain them, and safety concerns for the laboratory workers pose formidable challenges for rapid medical countermeasure discovery and evaluation. BSL-2 surrogate systems are a less challenging, cheap, and fast alternative to the use of live high-consequence viruses for dissecting and targeting individual steps of viral lifecycles with a diminished threat to the laboratory worker. Typical surrogate systems are virion-like particles (VLPs), transcriptionally active ("infectious") VLPs, minigenome systems, recombinant heterotypic viruses encoding proteins of target viruses, and vesiculoviral or retroviral pseudotype systems. Here, we outline the use of retroviral pseudotypes for identification of antivirals against BSL-4 pathogens. PMID- 28986851 TI - Protocols to Assess Coagulation Following In Vitro Infection with Hemorrhagic Fever Viruses. AB - During the course of infection with a hemorrhagic fever virus (HFV), the checks and balances associated with normal coagulation are perturbed resulting in hemorrhage in severe cases and, in some patients, disseminated intravascular coagulopathy (DIC). While many HFVs have animal models that permit the analyses of systemic coagulopathy, animal infection models do not exist for all HFVs and moreover do not always recapitulate the pathology observed in human tissues. Furthermore, molecular analyses of how coagulation is affected are not always straightforward or practical when using ex-vivo animal-derived samples, thus reinforcing the importance of cell culture studies. This chapter highlights procedures utilizing human umbilical vein endothelial cells (HUVECs) as a model system to evaluate components of the intrinsic (prekallikrein (PK), factor XII (FXII), kininogen, and bradykinin (BK)) and extrinsic (Tissue Factor (TF)) systems. Specifically, protocols are included for the generation of a coculture blood vessel model, plating and infection of HUVEC monolayers and assays designed to measure activation of PK and FXII, cleavage of kininogen, and to measure the expression of TF mRNA and protein. PMID- 28986852 TI - Effect of inspiratory synchronization during pressure-controlled ventilation on lung distension and inspiratory effort. AB - BACKGROUND: In pressure-controlled (PC) ventilation, tidal volume (V T) and transpulmonary pressure (P L ) result from the addition of ventilator pressure and the patient's inspiratory effort. PC modes can be classified into fully, partially, and non-synchronized modes, and the degree of synchronization may result in different V T and P L despite identical ventilator settings. This study assessed the effects of three PC modes on V T, P L , inspiratory effort (esophageal pressure-time product, PTPes), and airway occlusion pressure, P 0.1. We also assessed whether P 0.1 can be used for evaluating patient effort. METHODS: Prospective, randomized, crossover physiologic study performed in 14 spontaneously breathing mechanically ventilated patients recovering from acute respiratory failure (1 subsequently withdrew). PC modes were fully (PC-CMV), partially (PC-SIMV), and non-synchronized (PC-IMV using airway pressure release ventilation) and were applied randomly; driving pressure, inspiratory time, and set respiratory rate being similar for all modes. Airway, esophageal pressure, P 0.1, airflow, gas exchange, and hemodynamics were recorded. RESULTS: V T was significantly lower during PC-IMV as compared with PC-SIMV and PC-CMV (387 +/- 105 vs 458 +/- 134 vs 482 +/- 108 mL, respectively; p < 0.05). Maximal P L was also significantly lower (13.3 +/- 4.9 vs 15.3 +/- 5.7 vs 15.5 +/- 5.2 cmH2O, respectively; p < 0.05), but PTPes was significantly higher in PC-IMV (215.6 +/- 154.3 vs 150.0 +/- 102.4 vs 130.9 +/- 101.8 cmH2O * s * min-1, respectively; p < 0.05), with no differences in gas exchange and hemodynamic variables. PTPes increased by more than 15% in 10 patients and by more than 50% in 5 patients. An increased P 0.1 could identify high levels of PTPes. CONCLUSIONS: Non synchronized PC mode lowers V T and P L in comparison with more synchronized modes in spontaneously breathing patients but can increase patient effort and may need specific adjustments. Clinical Trial Registration Clinicaltrial.gov # NCT02071277. PMID- 28986855 TI - Outcome of in- and out-of-hospital cardiac arrest survivors with liver cirrhosis. AB - BACKGROUND: Organ failure increases mortality in patients with liver cirrhosis. Data about resuscitated cardiac arrest patients with liver cirrhosis are missing. This study aims to assess aetiology, survival and functional outcome in patients after successful cardiopulmonary resuscitation (CPR) with and without liver cirrhosis. METHODS: Analysis of prospectively collected cardiac arrest registry data of consecutively hospital-admitted patients following successful CPR was performed. Patient's characteristics, admission diagnosis, severity of disease, course of disease, short- and long-term mortality as well as functional outcome were assessed and compared between patients with and without cirrhosis. RESULTS: Out of 1068 patients with successful CPR, 47 (4%) had liver cirrhosis. Acute-on chronic liver failure (ACLF) was present in 33 (70%) of these patients on admission, and four patients developed ACLF during follow-up. Mortality at 1 year was more than threefold increased in patients with liver cirrhosis (OR 3.25; 95% CI 1.33-7.96). Liver cirrhosis was associated with impaired neurological outcome (OR for a favourable cerebral performance category: 0.13; 95% CI 0.04-0.36). None of the patients with Child-Turcotte-Pugh (CTP) C cirrhosis survived 28 days with good neurological outcome. Overall nine (19%) patients with cirrhosis survived 28 days with good neurological outcome. All patients with ACLF grade 3 died within 28 days. CONCLUSION: Cardiac arrest survivors with cirrhosis have worse outcome than those without. Although one quarter of patients with liver cirrhosis survived longer than 28 days after successful CPR, patients with CTP C as well as advanced ACLF did not survive 28 days with good neurological outcome. PMID- 28986854 TI - Altered Epigenetic Mechanisms in Thyroid Cancer Subtypes. AB - Thyroid carcinoma (TC) is the most frequent malignant neoplasm of the endocrine system. Molecular methods for diagnosis of invasive thyroid disease can be effectively adopted. Epigenetic factors play an important role in the diversity patterns of gene expression and the phenotypic and biological characteristics of TC subtypes. We aimed to review epigenetic changes in the main subtypes of TC, along with a presentation of the methods that have examined these changes, and active clinical trials for the treatment of advanced TCs targeting epigenetic changes. A literature analysis was performed in MEDLINE using PubMed, Elsevier, and Google Scholar for studies published up to 2016, using the keywords: "Epigenetic alterations" OR "Epigenetic changes", "thyroid cancers", "papillary thyroid cancer", "medullary thyroid cancer", "follicular thyroid cancer", and "anaplastic thyroid cancer", which resulted in 310 articles in English. All related abstracts were reviewed and studies were included that were published in English, had available full text, and determined the details of the methods and materials associated with the epigenetic patterns of TC and its subtypes (100 articles). Analysis of epigenetic alterations in TC subtypes helps to identify pathogenesis and can play an important role in the classification and diagnosis of tumors. Epigenetic mechanisms, especially aberrant methylation of DNA and microRNAs (miRs), are likely to play an important role in thyroid tumorigenesis. Further studies are required to elucidate the role of histone modification mechanisms in TC development. PMID- 28986856 TI - Spin Lattice Relaxation EPR pO2 Images May Direct the Location of Radiation Tumor Boosts to Enhance Tumor Cure. AB - Radiation treatment success and high tumor oxygenation and success have been known to be highly correlated. This suggests that radiation therapy guided by images of tumor regions with low oxygenation, oxygen-guided radiation therapy (OGRT) may be a promising enhancement of cancer radiation treatment. Before applying the technique to human subjects, OGRT needs to be tested in animals, most easily in rodents. Electron paramagnetic resonance imaging provides quantitative maps of tissue and tumor oxygen in rodents with 1 mm spatial resolution and 1 torr pO2 resolution at low oxygen levels. The difficulty of using mouse models is their small size and that of their tumors. To overcome this we used XRAD225Cx micro-CT/ therapy system and 3D printed conformal blocks. Radiation is delivered first to a uniform 15% tumor control dose for the whole tumor and then a boost dose to either hypoxic tumor regions or equal volumes of well oxygenated tumor. Delivery of the booster dose used a multiple beam angles to deliver radiation beams whose shape conforms to that of all hypoxic regions or fully avoids those regions. To treat/avoid all hypoxic regions we used individual radiation blocks 3D-printed from acrylonitrile butadiene styrene polymer infused with tungsten particles fabricated immediately after imaging to determine regions with pO2 less than 10 torr. Preliminary results demonstrate the efficacy of the radiation treatment with hypoxic boosts with syngeneic FSa fibrosarcoma tumors in the legs of C3H mice. PMID- 28986858 TI - Erratum to: Assessment of Energy Metabolic Changes in Adipose Tissue-Derived Stem Cells. PMID- 28986857 TI - Increased Sensitivity of Diagnostic Mutation Detection by Re-analysis Incorporating Local Reassembly of Sequence Reads. AB - BACKGROUND: Diagnostic genetic testing programmes based on next-generation DNA sequencing have resulted in the accrual of large datasets of targeted raw sequence data. Most diagnostic laboratories process these data through an automated variant-calling pipeline. Validation of the chosen analytical methods typically depends on confirming the detection of known sequence variants. Despite improvements in short-read alignment methods, current pipelines are known to be comparatively poor at detecting large insertion/deletion mutations. METHODS: We performed clinical validation of a local reassembly tool, ABRA (assembly-based realigner), through retrospective reanalysis of a cohort of more than 2000 hereditary cancer cases. RESULTS: ABRA enabled detection of a 96-bp deletion, 4 bp insertion mutation in PMS2 that had been initially identified using a comparative read-depth approach. We applied an updated pipeline incorporating ABRA to the entire cohort of 2000 cases and identified one previously undetected pathogenic variant, a 23-bp duplication in PTEN. We demonstrate the effect of read length on the ability to detect insertion/deletion variants by comparing HiSeq2500 (2 * 101-bp) and NextSeq500 (2 * 151-bp) sequence data for a range of variants and thereby show that the limitations of shorter read lengths can be mitigated using appropriate informatics tools. CONCLUSIONS: This work highlights the need for ongoing development of diagnostic pipelines to maximize test sensitivity. We also draw attention to the large differences in computational infrastructure required to perform day-to-day versus large-scale reprocessing tasks. PMID- 28986859 TI - The international Human Genome Project (HGP) and China's contribution. PMID- 28986860 TI - Correction to: New perspectives in nanotherapeutics for chronic respiratory diseases. AB - The original version of this article unfortunately contains an error. The third author's name "Patricia Rieken Macedo Rocco" was incorrectly spelled with "Roccco". The correct author name is now presented in the authorgroup. PMID- 28986861 TI - Ultrasound assessment of rectus femoris and anterior tibialis muscles in young trauma patients. AB - PURPOSE: Quantitative and qualitative changes of skeletal muscle are typical and early findings in trauma patients, being possibly associated with functional impairment. Early assessment of muscle changes-as evaluated by muscle ultrasonography-could yield important information about patient's outcome. METHODS: In this prospective observational study, we used ultrasonography to evaluate the morphological changes of rectus femoris (RF) and anterior tibialis (AT) muscles in a group of young, previously healthy trauma patients on enteral feeding. RESULTS: We studied 38 severely injured patients (median Injury Severity Score = 34; median age = 40 y.o.) over the course of the ICU stay up to 3 weeks after trauma. We found a progressive loss of muscle mass from day 0 to day 20, that was more relevant for the RF (45%) than for the AT (22%); this was accompanied by an increase in echogenicity (up to 2.5 by the Heckmatt Scale, where normal echogenicity = 1), which is an indicator of myofibers depletion. CONCLUSIONS: Ultrasound evaluation of skeletal muscles is inexpensive, noninvasive, simple and easily repeatable. By this method, we were able to quantify the morphological changes of skeletal muscle in trauma patients. Further studies may rely on this technicque to evaluate the impact of different therapeutic strategies on muscle wasting. PMID- 28986862 TI - Beyond the embolus: "do not miss" diffusion abnormalities of ischaemic and non ischaemic neurological disease. AB - : Given the rapid evolution and technological advances in the diagnosis and treatment of acute ischaemic stroke (AIS), including the proliferation of comprehensive stroke centres and increasing emphasis on interventional stroke therapies, the need for prompt recognition of stroke due to acute large vessel occlusion has received significant attention in the recent literature. Diffusion weighted imaging (DWI) is the gold standard for the diagnosis of acute ischaemic stroke, as images appear positive within minutes of ischaemic injury, and a high signal-to-noise ratio enables even punctate infarcts to be readily detected. DWI lesions resulting from a single arterial embolic occlusion or steno-occlusive lesion classically lateralise and conform to a specific arterial territory. When there is a central embolic source (e.g. left atrial thrombus), embolic infarcts are often found in multiple vascular territories. However, ischaemic disease arising from aetiologies other than arterial occlusion will often not conform to an arterial territory. Furthermore, there are several important entities unrelated to ischaemic disease that can present with abnormal DWI and which should not be confused with infarct. This pictorial review explores the scope and typical DWI findings of select neurologic conditions beyond acute arterial occlusion, which should not be missed or misinterpreted. TEACHING POINTS: * DWI abnormalities due to acute arterial occlusion must be promptly identified. * DWI abnormalities not due to arterial occlusion will often not conform to an arterial territory. * Several important non-ischaemic entities can present on DWI and should not be confused with infarct. PMID- 28986863 TI - Prognostic implications of blood lactate concentrations after cardiac arrest: a retrospective study. AB - BACKGROUND: Elevated lactate concentration has been associated with increased mortality after out-of-hospital cardiac arrest (CA). We investigated the variables associated with high blood lactate concentrations and explored the relationship between blood lactate and neurological outcome in this setting. METHODS: This was a retrospective analysis of an institutional database that included all adult (> 18 years) patients admitted to a multidisciplinary Department of Intensive Care between January 2009 and January 2013 after resuscitation from CA. Blood lactate concentrations were collected at hospital admission and 6, 12, 24 and 48 h thereafter. Neurological outcome was evaluated 3 months post-CA using the Cerebral Performance Category (CPC) score: a CPC of 3-5 was used to define a poor outcome. RESULTS: Of the 236 patients included, 162 (69%) had a poor outcome. On admission, median lactate concentrations (5.3[2.9 9.0] vs. 2.5[1.5-5.5], p < 0.001) and cardiovascular sequential organ failure assessment (cSOFA) score (3[0-4] vs. 0[0-3], p = 0.003) were higher in patients with poor than in those with favourable outcomes. Lactate concentrations were higher in patients with poor outcomes at all time points. Lactate concentrations were similar in patients with out-of-hospital and in-hospital CA at all time points. After adjustment, high admission lactate was independently associated with a poor neurological outcome (OR 1.18, 95% CI 1.08-1.30; p < 0.001). In multivariable analysis, use of vasopressors and high PaO2 on admission, longer time to return of spontaneous circulation and altered renal function were associated with high admission lactate concentrations. CONCLUSIONS: High lactate concentrations on admission were an independent predictor of poor neurological recovery post-CA, but the time course was not related to outcome. Prolonged resuscitation, use of vasopressors, high PaO2 and altered renal function were predictors of high lactate concentrations. PMID- 28986865 TI - NMDA Receptors in the Central Nervous System. AB - NMDA-type glutamate receptors are ligand-gated ion channels that mediate a major component of excitatory neurotransmission in the central nervous system (CNS). They are widely distributed at all stages of development and are critically involved in normal brain functions, including neuronal development and synaptic plasticity. NMDA receptors are also implicated in the pathophysiology of numerous neurological and psychiatric disorders, such as ischemic stroke, traumatic brain injury, Alzheimer's disease, epilepsy, mood disorders, and schizophrenia. For these reasons, NMDA receptors have been intensively studied in the past several decades to elucidate their physiological roles and to advance them as therapeutic targets. Seven NMDA receptor subunits exist that assemble into a diverse array of tetrameric receptor complexes, which are differently regulated, have distinct regional and developmental expression, and possess a wide range of functional and pharmacological properties. The diversity in subunit composition creates NMDA receptor subtypes with distinct physiological roles across neuronal cell types and brain regions, and enables precise tuning of synaptic transmission. Here, we will review the relationship between NMDA receptor structure and function, the diversity and significance of NMDA receptor subtypes in the CNS, as well as principles and rules by which NMDA receptors operate in the CNS under normal and pathological conditions. PMID- 28986864 TI - Sex-Specific Epigenetics: Implications for Environmental Studies of Brain and Behavior. AB - PURPOSE OF REVIEW: This review discusses the current state of knowledge on sex differences in the epigenetic regulation in the brain and highlights its relevance for the environmental studies of brain and behavior. RECENT FINDINGS: Recent evidence shows that epigenetic mechanisms are involved in the control of brain sexual differentiation and in memory-enhancing effects of estradiol in females. In addition, several studies have implicated epigenetic dysregulation as an underlying mechanism for sex-specific neurobehavioral effects of environmental exposures. The area of sex-specific neurepigenetics has a great potential to improve our understanding of brain function in health and disease. Future neuropigenetic studies will require the inclusion of males and females and would ideally account for the fluctuating hormonal status in females which is likely to affect the epigenome. The implementation of cutting-edge methods that include epigenomic characterization of specific cell types using latest next-generation sequencing approaches will further advance the area. PMID- 28986866 TI - Quantification of NMDAR Subunit Genes Expression by qRT-PCR. AB - Transcription is the initial and generally the most sensitive step to cellular needs and environmental cues. Thus, it serves as a major mechanism controlling gene expression. Using reverse-transcription quantitative polymerase chain reaction technology (RT-qPCR), we will present how to quantify the transcriptional expression of NMDARs subunits during brain development and in both healthy and pathological conditions. PMID- 28986868 TI - Detection of NMDARs Antibodies in Encephalitis. AB - There is a range of diseases of the brain that are associated with rapidly developing inflammation. These conditions are called encephalitis, and can be caused by infections, or autoimmune disorders when the subject's immune system reacts against host proteins. The most common form of autoimmune encephalitis is associated with antibodies against the NR1 subunit of the N-Methyl-D-Aspartate Receptor (anti-NMDAR-encephalitis). Antibody detection is important for diagnosis, and can be performed only with techniques that preserve the full tertiary structure (conformation) of the antigen. Here, we describe the methods commonly used to detect NMDAR-antibodies with immunohistochemistry on rat brain slices and on live HEK cells transfected with components of the NMDAR. PMID- 28986867 TI - Genetic and Functional Analysis of GRIN2A in Tumor Samples. AB - Ionotropic glutamate receptors (iGluRs) are large integral membrane multi-protein complexes that create ion channels in plasma membranes. Upon binding of receptor specific ligands (e.g., glutamate), increased efflux or influx of mono- or divalent cations (e.g., Ca2+) promotes synaptic transmission, cellular migration, and survival. Three classes of iGluRs were originally defined after their respective agonists: AMPA, kainate, and NMDA receptors (NMDARs). Recently, we examined iGluR families at the genetic level using Next-Generation Sequencing (NGS) (whole-exome sequencing (WES)) and discovered a high prevalence of somatic mutations within the gene for one of the NMDAR subunits, GRIN2A, specifically in malignant melanoma. Following confirmation of the somatic mutations, we focused on functional characterization of a subset of the GRIN2A mutants that demonstrated a loss of NMDAR functionality. We used gene expression and protein biochemistry to examine complex formation between GluN1 subunit (encoded by GRIN1) and GluN2A subunit (encoded by GRIN2A), anchorage-independent growth in soft agar and cellular migration. Furthermore, we used shRNA depletion of endogenous GRIN2A in melanoma cells expressing either wild-type GRIN2A or mutant GRIN2A and measured cellular proliferation compared to negative controls. Our data show that somatic mutation of certain residues in GluN2A results in increased survival and is the first such report to demonstrate the functional importance of GRIN2A mutations in melanoma and the significance ionotropic glutamate receptor signaling plays in malignant melanoma. PMID- 28986869 TI - MagnetofectionTM of NMDA Receptor Subunits GluN1 and GluN2A Expression Vectors in Non-Neuronal Host Cells. AB - The functional study of reconstituted NMDA receptors (NMDARs) in host cells requires that the corresponding vectors for the expression of the NMDAR subunits are co-transfected with high efficiency. MagnetofectionTM is a technology used to deliver nucleic acids to cells. It is driven and site-specifically guided by the attractive forces of magnetic fields acting on magnetic nanoparticles that are associated with nucleic acid vectors. In magnetofectionTM, cationic lipids form self-assembled complexes with the nucleic acid vectors of interest. Those complexes are then associated with magnetic nanoparticles that are concentrated at the surface of cultured cells by applying a permanent magnetic field. MagnetofectionTM is a simple method to transfect cultured cells with high transfection rates. Satisfactory expression levels are obtained with very low amounts of nucleic acid vector. Moreover, incubation time with host cells is less than 1 h, as compared with the several hours needed with standard transfection assays. PMID- 28986870 TI - Transfection in Primary Cultured Neuronal Cells. AB - Transfection allows the introduction of foreign nucleic acid into eukaryotic cells. It is an important tool in understanding the roles of NMDARs in neurons. Here, we describe using lipofection-mediated transfection to introduce cDNA encoding NMDAR subunits into postmitotic rodent primary cortical neurons maintained in culture. PMID- 28986871 TI - Selective Cell-Surface Expression of Triheteromeric NMDA Receptors. AB - The NMDA-type ionotropic glutamate receptors play pivotal roles in many brain functions, but are also involved in numerous brain disorders. Seven NMDA receptor subunits exist (GluN1, GluN2A-D, and GluN3A-B) that assemble into a diverse array of tetrameric receptor subtypes with distinct functional properties and physiological roles. Most NMDA receptors are composed of two GluN1 and two GluN2 subunits, which can assemble into four diheteromeric receptor subtypes composed of GluN1 and one type of GluN2 subunit (e.g., GluN1/2A), and presumably also six triheteromeric receptor subtypes composed of GluN1 and two different GluN2 subunits (e.g., GluN1/2A/2B). Despite accumulating evidence that a large proportion of native NMDA receptors are triheteromers, little is known about their function and pharmacology due to the lack of methods to faithfully express triheteromeric NMDA receptors in heterologous expression systems. The problem is that co-expression of GluN1 with two different GluN2 subunits generates two distinct diheteromeric receptor subtypes as well as one triheteromeric receptor subtype, thereby confounding studies on a homogenous population of triheteromeric NMDA receptors. Here, we will describe a method to selectively express recombinant triheteromeric GluN1/2A/2B receptors without interfering co expression of diheteromeric GluN1/2A and GluN1/2B receptors. This method enables quantitative evaluation of functional and pharmacological properties of triheteromeric GluN1/2A/2B receptors, which are presumably the most abundant NMDA receptors in the adult cortex and hippocampus. PMID- 28986872 TI - Functional Analysis of Recombinant Channels in Host Cells Using a Fast Agonist Application System. AB - A reduced recombinant system provides a unique opportunity to study the biophysical properties of NMDAR channels with known subunit compositions, by using a point mutation approach to analyze the structural determinants of receptor function (Wollmuth and Sobolevsky, Trends Neurosci 27:321-328, 2004). However, in addition to the well-developed repertoire of molecular biological techniques, these types of studies also require electrophysiological methods that allow a wide range of receptor activation protocols that can adequately assess desensitization, inactivation, ion permeability, and other properties of the channels. Currently, one of the most well-developed techniques suitable for addressing these issues is use of the fast agonist application system for rapid activation of ligand gated ion-channels (Colquhoun et al., J Physiol 458:261-287, 1992; Jonas and Sakmann, J Physiol 455:143-171, 1992). PMID- 28986873 TI - GluN2B Subunit Labeling with Fluorescent Probes and High-Resolution Live Imaging. AB - Laser Scanning Confocal Microscopy (LSCM) imaging using an appropriate fluorescent probe enables the visualization of a molecular target with high resolution, and represents a method of choice for studying expression, subcellular location, and trafficking of receptors in living cells. The chemical, physical, and pharmacological properties of the probe remain essential. Here, we describe (1) the preparation of a specific probe for NMDAR GluN2B receptor by conjugation of fluorescein to an ifenprodil-based ligand, (2) an in vitro functional assay by calcium imaging for GluN2B binding and inhibition evaluation of the probe, and (3) the labeling and confocal imaging of GluN2B in DS-red labeled living cortical neurons. PMID- 28986874 TI - Design of Light-Sensitive NMDARs by Genetically Encoded Photo-Cross-Linkers. AB - Genetic code expansion exploiting unnatural amino acids (Uaas) is a powerful technique to create novel protein function in vivo. Here, we provide a protocol for the incorporation of two UV-sensitive crosslinking Uaas into NMDA receptors (NMDARs), a type of glutamate-gated ion channels mediating fast synaptic transmission. Through heterologous expression in Xenopus laevis oocytes, we have identified light-sensitive NMDARs of GluN2B subtype by using the two-electrode voltage electrophysiology measurement in combination with online-UV application. Immunoblotting analysis has been used to confirm inter-subunit crosslinking. PMID- 28986875 TI - Gene Targeted Mice with Conditional Knock-In (-Out) of NMDAR Mutations. AB - For the genetic alterations of NMDA receptor (NMDAR) properties like Ca2+ permeability or voltage-dependent gating in mice and for the experimental analysis of nonsense or missense mutations that were identified in human patients, single nucleotide mutations have to be introduced into the germ line of mice (Burnashev and Szepetowski, Curr Opin Pharmacol 20:73-82, 2015; Endele et al., Nat Genet 42:1021-1026, 2010). This can be done with very high precision by the well-established method of gene replacement, which makes use of homologous recombination in pluripotent embryonic stem (ES) cells of mice. The homologous recombination at NMDAR subunit genes (Grin; for glutamate receptor ionotropic NMDAR subtype) has to be performed by targeting vectors, also called replacement vectors. The targeting vector should encode part of the gene for the NMDAR subunit, the NMDAR mutation, and a removable selection maker. In these days, the targeting vector can be precisely designed using DNA sequences from public databases. The assembly of the vector is then done from isogenic NMDAR gene fragments cloned in bacterial artificial chromosomes (BACs) using "high fidelity" long-range PCR reactions. During these PCR reactions, the NMDAR mutations are introduced into the cloned NMDAR gene fragments of the targeting vector. Finally, the targeting vector is used for homologous recombination in mouse ES cells. Positive ES cell clones which have the correct mutation have to be selected and are then used for blastocyst injection to generate chimeric mice that hopefully transmit the Grin gene targeted ES cells to their offspring. In the first offspring generation of the founder (F1), some animals will be heterozygous for the targeted NMDAR gene mutation. In order to regulate the expression of NMDAR mutations, it is important to keep the targeted NMDAR mutation under conditional control. Here, we describe a general method how those conditionally controlled NMDAR mutations can be engraved into the germ line of mice as hypomorphic Grin alleles. By breeding these hypomorphic Grin gene targeted mice with Cre recombinase expressing mice, the hypomorphic Grin allele can be activated at specific time points in specific cell types, and the function of the mutated NMDAR can be analyzed in these - so called - conditional mouse models. In this method chapter, we describe in detail the different methodical steps for successful gene targeting and generation of conditional NMDAR mutant mouse lines. Within the last 20 years, several students in our Department of Molecular Neurobiology in Heidelberg used these techniques several times to generate different mouse lines with mutated NMDARs. PMID- 28986876 TI - Electrophysiological Investigation of NMDA Current Properties in Brain Slices. AB - Analysis of electrophysiological properties of NMDARs and NMDAR-mediated synaptic transmission in identified neurons and synapses in brain slices is a major step in understanding their function in normal and pathological neuronal brain networks. In many central synapses excitatory postsynaptic currents (EPSCs) are mediated by excitatory neurotransmitter glutamate that activates colocalized AMPAR and NMDAR generating a complex EPSC. Here, we describe the methods commonly used in brain slices to study the electrophysiological properties of NMDAR mediated component of spontaneous or evoked EPSCs by extracellular stimulation or by stimulating synaptically connected neurons. This approach is based on whole cell patch-clamp recordings, pharmacological tools, and the analysis of the difference in temporal parameters between the AMPA and NMDA receptors. It allows pinpointing of the basic functional properties of NMDARs that are specific to identified brain regions, neurons, and synapses of wild-type or genetically manipulated mice. PMID- 28986877 TI - Analysis of Functional NMDA Receptors in Astrocytes. AB - Neuronal N-methyl-D-aspartate (NMDA) receptors are well known for their pivotal role in memory formation. Originally, they were thought to be exclusive to neurons. However, numerous studies revealed their functional expression also on various types of glial cells in the nervous system. Here, the methodology how to study the physiology of NMDA receptors selectively on astrocytes will be described in detail. Astrocytes are the main class of neuroglia that control transmitter and ion homeostasis, which link cerebral blood flow and neuronal energy demands, but also affect synaptic transmission directly. PMID- 28986878 TI - GluNs Detection and Functions in Microglial Cells. AB - Proving endogenous GluN presence and functions in microglia require complementary steps to demonstrate (1) that GluN genes are transcripted and translated, (2) their cellular localization, (3) that the GluN are functional, and (4) the role of the functional GluN. The complete demonstration is performed by using mRNA detection technics, western blots, immunofluorescence, electrophysiology, calcium imaging, morphology studies, multiplex immunoassay together with conditional microglial Knock-Out mice and brain lesion models. PMID- 28986879 TI - NMDA Receptor Activity in Circulating Red Blood Cells: Methods of Detection. AB - Abundance and activity of N-methyl-D-aspartate (NMDA) in circulating red blood cells contributes to the maintenance of intracellular Ca2+ in these cells and, by doing that, controls red cell volume, membrane stability, and O2 carrying capacity. Detection of the NMDA receptor activity in red blood cells is challenging as the number of its copies is low and shows substantial cell-to-cell heterogeneity. Receptor abundance is reliably assessed using the radiolabeled antagonist ([3H]MK-801) binding technique. Uptake of Ca2+ following the NMDA receptor activation is detected in cells loaded with Ca2+-sensitive fluorescent dye Fluo-4 AM. Both microfluorescence live-cell imaging and flow cytometry may be used for fluorescence intensity detection. Automated patch clamp is currently used for recording of electric currents triggered by the stimulation of the NMDA receptor. These currents are mediated by the Ca2+-sensitive K+ (Gardos) channels that open upon Ca2+ uptake via the active NMDA receptor. Furthermore, K+ flux through the Gardos channels induced by the NMDA receptor stimulation in red blood cells may be detected using unidirectional K+(86Rb+) influx. PMID- 28986880 TI - NMDA Receptors as Voltage Sensors. AB - The membrane potential is an essential parameter of a living cell. However, measurements of the membrane potential using conventional techniques are associated with a number of artifacts. Cell-attached recordings of the currents through NMDA receptor channels enable noninvasive measurements of the neuronal membrane potential. This approach overcomes the problem of a leak conductance introduced during intracellular sharp electrode recordings and whole-cell patch clamp recordings. Here, we describe the procedures of using cell-attached recordings of NMDA receptor channels to measure the true membrane potential. PMID- 28986881 TI - Development of a Computational Approach/Model to Explore NMDA Receptors Functions. AB - Modern laboratory techniques allow studying NMDA receptors (NMDAR) either anatomically with specific antibodies coupled to sophisticated confocal microscopy, or physiologically by live imaging or electrophysiological techniques. However, NMDARs are not fixed in time and space and changes in their composition and/or distribution on the post-synaptic membrane may significantly impact the synaptic strength and overall function. The computational modeling approach therefore constitutes a complementary tool for investigating the properties of biological systems based on the knowledge provided by the lab experiments.Here, we describe a general computational method aiming at developing kinetic Markov-chain based models of NMDARs subtypes capable of reproducing various experimental results. These models are then used to make predictions on additional (non-obvious) properties and on their role in synaptic function under various physiological and pharmacological conditions. For the purpose of this book chapter, we will focus on the method used to develop a NMDAR model that includes pharmacological site of action of different compounds. Notably, this elementary model can subsequently be included in a neuron model (not described in detail here) to explore the impact of their differential distribution on synaptic functions. PMID- 28986882 TI - Introduction to Cancer Stem Cells: Past, Present, and Future. AB - The Cancer Stem Cell (CSC) hypothesis postulates the existence of a small population of cancer cells with intrinsic properties allowing for resistance to conventional radiochemotherapy regiments and increased metastatic potential. Clinically, the aggressive nature of CSCs has been shown to correlate with increased tumor recurrence, metastatic spread, and overall poor patient outcome across multiple cancer subtypes. Traditionally, isolation of CSCs has been achieved through utilization of cell surface markers, while the functional differences between CSCs and remaining tumor cells have been described through proliferation, differentiation, and limiting dilution assays. The generated insights into CSC biology have further highlighted the importance of studying intratumoral heterogeneity through advanced functional assays, including CRISPR Cas9 screens in the search of novel targeted therapies. In this chapter, we review the discovery and characterization of cancer stem cells populations within several major cancer subtypes, recent developments of novel assays used in studying therapy resistant tumor cells, as well as recent developments in therapies targeted at cancer stem cells. PMID- 28986883 TI - Surface Markers for the Identification of Cancer Stem Cells. AB - Cancer stem cells have genetic and functional characteristics that can turn them resistant to standard cancer therapeutic targets. Identification of these cells is challenging and is mostly done by detecting the expression of their antigens in a group of stem cells. Currently, there are a significant number of surface markers available which can detect the cancer stem cells by directly targeting their specific antigens present in cells. These markers possess differential expression patterns and sub-localizations in cancer stem cells when compared to non-neoplastic stem cells and somatic cells. In addition to molecular markers, multiple analytical methods and techniques including functional assays, cell sorting, filtration approaches, and xenotransplantation methods are used to identify cancer stem cells. This chapter will overview the functional significance of cancer stem cells, its biological correlations, specific markers, and detection methods. PMID- 28986884 TI - The Role of CD44 and Cancer Stem Cells. AB - Solid tumors are composed of mutually interacting cancer cells and tumor microenvironment. Many environmental components, such as extracellular matrix (ECM), mesenchymal stem cells, endothelial and immune cells, and various growth factors and cytokines, provide signals, either stimulatory or inhibitory, to cancer cells and determine their fates. Meanwhile, cancer cells can also educate surrounding cells or tissues to undergo changes that are in favorable of tumor progression. CD44, as a transmembrane receptor for hyaluronic acid (HA) and many other ECM components and a coreceptor for growth factors and cytokines, is a critical cell surface molecule that can sense, integrate, and transduce cellular microenvironmental signals to membrane-associated cytoskeletal proteins or to cell nucleus to regulate a variety of gene expressions that govern cell behaviors. Mounting evidence suggests that CD44, particularly CD44v isoforms, are cancer stem cell (CSC) markers and critical regulators of cancer stemness, including self-renewal, tumor initiation, and metastasis. Thus, CD44 is widely used alone or in combination with other cell surface markers to isolate or enrich CSCs through fluorescence-activated cell sorting of dissociated single cells that originate from the patient, xenograft tumor tissues, or tumor cell cultures. Sorted cells are cultured in a specialized culture medium for spheroid formation or inoculated into immunodeficient mice for the analysis of tumorigenic or metastatic potential. In this chapter, detailed experimental methods regarding CD44+ tumor cell isolation, spheroid culture, and characterization will be described. PMID- 28986885 TI - Evaluation and Isolation of Cancer Stem Cells Using ALDH Activity Assay. AB - The aldehyde dehydrogenase (ALDH) is a polymorphic enzyme responsible for the oxidation of aldehydes to carboxylic acids. In this chapter, it is described the role of ALDH in the identification of cancer stem cells (CSCs), having been shown that stem cells express high levels of ALDH. Here, we present a method called ALDEFLUOR assay used for the identification, evaluation, and isolation of normal, cancer stem and progenitor cells. PMID- 28986886 TI - Isolation of Cancer Stem Cells by Side Population Method. AB - The Hoechst side population (SP) method is a flow cytometry technique used to obtain stem cells based on the dye efflux properties of the ATP-binding cassette (ABC) transporters. The SP cells are characterized by their capability to efflux the fluorescent DNA-binding dye Hoechst 33342 through their ABC transporters and are enriched in stem cells, which are endowed with a self-renewal capacity and multilineage differentiation potential and express the stemness genes including ABC multidrug transporters. The protocols outlined in this book chapter describe the isolation method of the SP cells from human lung carcinoma cell lines by using Hoechst 33342. In addition, we refer to the propagation method of SP cells by successive rounds of fluorescence-activated cell sorting analysis for SP cells. These approaches will be helpful for the establishment of novel in vitro and in vivo models using cancer stem cells, which may play a key role during carcinogenesis and/or tumor progression. PMID- 28986887 TI - Self-Renewal and CSCs In Vitro Enrichment: Growth as Floating Spheres. AB - Cancer stem cells (CSC) are a vital component to the progression and reoccurrence of cancers, making them a primary target of study for both fundamental understanding of cancer biology and the development of effective and targeted treatments. CSCs reside in a complex 3D microenvironment, and the 3D spheroids are an indispensable tool in tumor biology due to their 3D structure and replication of the tumor microenvironment. Within this chapter the methodology for CSC isolation, suspension culture in hanging drop model, and characterization assays for CSC are described. First, the methodology for identifying and isolating CSCs from patient tumors, ascites, or cancer cell lines is described through the use of FACS analysis. Next, a detailed description of 3D hanging drop model for generating CSC spheroids is provided, followed by maintenance and monitoring techniques for extended 3D culture. Analysis methods are described for the quantification of CSC spheroid proliferation and viability tracking, throughout culture by on-plate alamarBlue fluorescence. Additional viability assays are described utilizing confocal microscopy with Live/Dead Viability/Cytotoxicity Kit. The characterization of CSCs populations within spheroids is described through FACS analysis. Further, an immunohistochemistry procedure is described for cell-cell and cell-matrix interaction assessment. Finally, several notes and tips for successful experiments with 3D CSC spheroids on the hanging drop model are provided. These methods are not only applicable to CSCs within a variety of tumor cell types, for not only understanding the fundamental tumor biology, but also for drug screening and development of preclinical chemotherapeutic strategies. PMID- 28986888 TI - In Vitro Tumorigenic Assay: The Tumor Spheres Assay. AB - Cancer stem cells (CSCs) are a subpopulation of cells within cancer tissues that are thought to mediate tumor initiation. CSCs are furthermore considered the cause of tumor progression and recurrence after conventional therapies, based on their enhanced therapy resistance properties. A method commonly used to assess CSC potential in vitro is the so-called tumor spheres assay in which cells are plated under non-adherent culture conditions in serum-free medium supplemented with growth factors. Tumor spheres assays have been used in cancer research as an intermediate in vitro cell culture model to be explored before performing more laborious in vivo tumor xenograft assays. PMID- 28986889 TI - In Vitro Tumorigenic Assay: Colony Forming Assay for Cancer Stem Cells. AB - Colony forming or clonogenic assay is an in vitro quantitative technique to examine the capability of a single cell to grow into a large colony through clonal expansion. Clonogenic activity is a sensitive indicator of undifferentiated cancer stem cells. Here, we described the colony forming ability of the isolated breast cancer stem cells from the total population of cancer cells using double-layered, soft agarose-based assay. This method demonstrates that cancer stem cells can survive and generate colony growth in an anchorage independent culture model. The 0.005% crystal violet solution is used in this assay to visualize the generated colonies. PMID- 28986890 TI - Xenograft as In Vivo Experimental Model. AB - The identification of experimental models that recapitulate human cancers designed to predict patient clinical response to therapies is a major break in oncology. Cancer stem cells (CSCs) represent a small tumor cell population responsible for drug resistance, where their effective killing may lead to identifying better treatment options. While the CSCs hypothesis highlights the need for a specific tumor target, patient-derived xenografts (PDXs) should also be considered for drug development as they better represent tumor heterogeneity and the environment in which a tumor develops. PMID- 28986891 TI - How to Assess Drug Resistance in Cancer Stem Cells. AB - Banks of genetically characterized cancer stem cells (CSCs) isolated from individual patients and grown as spheroids offer an invaluable approach to identify genetic determinants of drug resistance versus sensitivity, and to study new stem cell-directed therapies. Here, we describe our standardized procedure for in vitro drug screening on colorectal CSCs, taking irinotecan as an example. PMID- 28986892 TI - Tumor Tissue Analogs for the Assessment of Radioresistance in Cancer Stem Cells. AB - Over the years, radiotherapy-related research has been based on local tumor control as an experimental endpoint, yielding a wealth of data demonstrating the importance of cancer stem cells in tumor reoccurrence after radiotherapy. Literature is replete with experimental and clinical evidence that the cancer stem cell population in a tumor affects its radiocurability. An important consideration for radiotherapy is the microenvironmental stimuli in the CSC niche that results from factors such as hypoxia, extracellular matrix (ECM) elements and their intercellular interaction with non-stem cells and other cell types that prevail in the tumor milieu. In this chapter, we have described the methodology to develop in vitro 3D tumor models that incorporate these microenvironmental characteristics and design experiments that generate endpoints for understanding radioresistance in cancer stem cells. PMID- 28986893 TI - Generation of In Vitro Model of Epithelial Mesenchymal Transition (EMT) Via the Expression of a Cytoplasmic Mutant Form of Promylocytic Leukemia Protein (PML). AB - Epithelial Mesenchymal Transition (EMT) is a key event in cancer progression. During this event, epithelial cancer cells undergo molecular and cellular changes leading to their trans-differentiation into mesenchymal cancer cells that are capable of migration, invasion, and metastasis to other tissues and organs. Here, we present a method for in vitro induction of EMT in prostate cancer cell lines using lentiviral expression of a PMLI isoform mutant construct. PMID- 28986894 TI - Identification and Isolation of Cancer Stem Cells Using NANOG-EGFP Reporter System. AB - Cancer stem Cells or Cancer Stem-like Cells are thought to be associated with chemoresistance and recurrence in cancer patients following chemotherapy. Developing a method to study these malignant populations is the key to successful development of drug or immunotherapeutic assays. Here, we present a method of identification, isolation of Prostate Cancer Stem Cells (PCSCs) from the DU145 prostate cancer cell line using the NANOG-GFP expression system. PMID- 28986895 TI - Determination of miRNAs from Cancer Stem Cells Using a Low Density Array Platform. AB - A microarray approach has been extensively used for global gene expression profiles in many biological research fields such as understanding of pathological mechanism in malignancies and defining of molecular biomarkers to monitor disease status. The most attractive advantage of microarray technology is its application to simultaneous analysis of miRNA expression pattern with a large amount of assessments. In this chapter, we provide a facile and universal protocol for divergent miRNA expression profiles in prostate cancer stem cells with a low density array-based microarray analysis. PMID- 28986896 TI - Assessing DNA Methylation in Cancer Stem Cells. AB - Many cancer-associated epigenetic signatures are also commonly observed in stem cells, just as epigenetic stem cell patterns are in cancer cells. DNA methylation is recognized as a hallmark of cancer development and progression. Herein, we describe two approaches to analyze DNA methylation, which can be applied to study or discover DNA methylation aberrations throughout the genome, as well as a more targeted investigation of regions of interest in cancer stem cells. PMID- 28986898 TI - Immunohistochemistry for Cancer Stem Cells Detection: Principles and Methods. AB - Cancer stem cells (CSCs) are rare immortal cells within a tumor that can self renew and drive tumorigenesis. CSCs play a pivotal role in the tumor development, progression and relapse, as well as in the resistance of anticancer therapy. Different tools could help in the analysis of CSCs, especially Immunohistochemistry (IHC) represents a useful technique able to identify several specific CSC markers. The main aims of this chapter are the description of the explain immunohistochemical methods used in the characterization of CSCs. Furthermore, focus on the most common troubleshooting in CSCs IHC is provided, especially the pitfalls of the CSCs markers IHC on tissue microarrays. PMID- 28986897 TI - Histones Acetylation and Cancer Stem Cells (CSCs). AB - Chromatin decondensation is a key mechanism that guarantees gene transcription and repair of the genome, regulated mainly by the acetylation of histones. Emerging evidence has pointed out to histones as a new controlling mechanism of stem cell maintenance and fate. In this chapter, we will focus on the methods used to enrich tumor cell lines for cancer stem cells, and in the methods to identify the status of the histone acetylation in cancer cells and stem cells using immunofluorescence, invasion, and adhesion assays and identification of nuclear size. PMID- 28986899 TI - Circulating Tumor Cells. AB - In most solid tumors, it is distant metastases rather than the primary tumor which limit the prognosis. Distant metastases are caused by circulating tumor cells (CTCs) which actively invade the blood stream, attach to the endothelium in the target organ, invade the surrounding parenchyma, and form new tumors. Among many other capabilities such as migration or immune escape, CTCs require tumor forming capacities and can therefore be considered stem cell-like cells. This chapter describes the enrichment and isolation of live CTCs from clinical blood samples for molecular characterization and other downstream applications. PMID- 28986901 TI - Use of In Vitro Kernel Culture to Study Maize Nitrogen and Carbohydrate Metabolism. AB - Grain yield in maize is the result of a genotype's response to environmental conditions and agronomic management. However, whether in a field, greenhouse, or growth chamber, plant-to-plant variation exists within the same genotype, necessitating large amounts of plants and growth area to determine a metabolic response to a change in growth conditions or fertilizer supply. Additionally, because of whole-plant interactions in the supply of nutrients to kernels, it is difficult to study assimilate or temperature effects on the growth of kernels. The in vitro growth of kernels is one way to circumvent this problem because it allows for kernel growth under defined conditions of nutrient supply, while minimizing environmental and maternal influences. The in vitro kernel culturing method can be used to identify source: sink relationships, assimilate transport, metabolism, plant growth regulators, and other physiological responses by altering the source supply to individual kernels within an ear, thereby reducing or controlling environmental effects, while maintaining kernel-cob and organ-wide interactions. A single control-pollinated immature maize ear can be divided and quickly subjected to various growth conditions using liquid media to more precisely generate physiological and metabolic changes in the earshoot than in planta. PMID- 28986900 TI - Patients' preferences for headache acute and preventive treatment. AB - BACKGROUND: We aimed to explore patients' preferences for headache treatments with a self-administered questionnaire including the Q-No questionnaire for nocebo. METHODS: Questionnaires from 514 outpatients naive to neurostimulation and monoclonal antibodies were collected. RESULTS: Patients assessed that the efficacy of a treatment is more important than safety or route of administration. They preferred to use an external neurostimulation device for both acute (67.1%) and preventive treatment (62.8%). Most patients preferred to take a pill (86%) than any other drug given parenterally for symptomatic pharmaceutical treatment. For preventive pharmaceutical treatment, most patients preferred to take a pill once per day (52%) compared to an injection either subcutaneously or intravenously each month (9% and 4%), or three months (15% and 11%). 56.6% of all participants scored more than 15 in Q-No questionnaire indicating potential nocebo behaviors that contributed significantly in their choices. CONCLUSION: These patient preferences along with efficacy and safety data may help physicians better choose the right treatment for the right person. PMID- 28986902 TI - Agrobacterium- and Biolistic-Mediated Transformation of Maize B104 Inbred. AB - Genetic transformation of maize inbred genotypes remains non-routine for many laboratories due to variations in cell competency to induce embryogenic callus, as well as the cell's ability to receive and incorporate transgenes into the genome. This chapter describes two transformation protocols using Agrobacterium- and biolistic-mediated methods for gene delivery. Immature zygotic embryos of maize inbred B104, excised from ears harvested 10-14 days post pollination, are used as starting explant material. Disarmed Agrobacterium strains harboring standard binary vectors and the biolistic gun system Bio-Rad PDS-1000/He are used as gene delivery systems. The herbicide resistant bar gene and selection agent bialaphos are used for identifying putative transgenic type I callus events. Using the step-by-step protocols described here, average transformation frequencies (number of bialaphos resistant T0 callus events per 100 explants infected or bombarded) of 4% and 8% can be achieved using the Agrobacterium- and biolistic-mediated methods, respectively. An estimated duration of 16-21 weeks is needed using either protocol from the start of transformation experiments to obtaining putative transgenic plantlets with established roots. In addition to laboratory in vitro procedures, detailed greenhouse protocols for producing immature ears as transformation starting material and caring for transgenic plants for seed production are also described. PMID- 28986903 TI - Advances in Agrobacterium-mediated Maize Transformation. AB - One of the major limitations of maize transformation is the isolation of a large number of immature embryos using the time-consuming manual extraction method. In this article, we describe a novel bulk embryo extraction method for fast isolation of a large number of embryos suitable for both biolistic- and Agrobacterium-mediated transformation. Optimal gene delivery and tissue culture conditions are also described for achieving high efficiency in Agrobacterium mediated maize transformation using phosphomannose isomerase (PMI) as a selectable marker. PMID- 28986904 TI - A Brief History of Promoter Development for Use in Transgenic Maize Applications. AB - Promoters regulate gene expression, and are essential biotechnology tools. Since its introduction in the mid-1990s, biotechnology has greatly enhanced maize productivity primarily through the development of insect control and herbicide tolerance traits. Additional biotechnology applications include improving seed nutrient composition, industrial protein production, therapeutic production, disease resistance, abiotic stress resistance, and yield enhancement. Biotechnology has also greatly expanded basic research into important mechanisms that govern plant growth and reproduction. Many novel promoters have been developed to facilitate this work, but only a few are widely used. Transgene optimization includes a variety of strategies some of which effect promoter structure. Recent reviews examine the state of the art with respect to transgene design for biotechnology applications. This chapter examines the use of transgene technology in maize, focusing on the way promoters are selected and used. The impact of new developments in genomic technology on promoter structure is also discussed. PMID- 28986905 TI - Deletion Mutagenesis and Identification of Causative Mutations in Maize. AB - We describe a method for gamma-irradiation of mature maize seeds to generate mutants with opaque endosperm and reduced kernel fill phenotypes. We also describe methods for mapping mutants and identifying causal gene mutations. Using this method, a population of 1788M2 families and 47 Mo17 * F2s showing stable, segregating, and viable kernel phenotypes was developed. For molecular characterization of the mutants, we utilized a novel functional genomics platform that combines separate Bulked Segregant RNA and exome sequencing data sets (BSREx seq) to map causative mutations and identify candidate genes within mapping intervals. We also describe the use of exome capture sequencing of F2 mutant and normal pools to perform mapping and candidate gene identification without the need for separate RNA-seq (BSEx-seq). To exemplify the utility of the deletion mutants for functional genomics and provide proof-of-concept for the bioinformatics platform, we summarize the identification of the causative deletion in two mutants. Mutant 937, which was characterized by BSREx-seq, harbors a 6203-bp in-frame deletion covering six exons within the Opaque-1 gene on chromosome 4. Preliminary investigation of opaque mutant 1486 with BSEx-seq shows a tight mapping interval and associated deletion on chromosome 10. PMID- 28986907 TI - Virus-Induced Gene Silencing in Maize with a Foxtail mosaic virus Vector. AB - Virus-induced gene silencing (VIGS) is a powerful technology for rapidly and transiently knocking down the expression of plant genes to study their functions. A VIGS vector for maize derived from Foxtail mosaic virus (FoMV), a positive sense single-stranded RNA virus, was recently developed. A cloning site created near the 3' end of the FoMV genome enables insertion of 200-400 nucleotide fragments of maize genes targeted for silencing. The recombinant FoMV clones are inoculated into leaves of maize seedlings by biolistic particle delivery, and silencing is typically observed within 2 weeks after inoculation. This chapter provides a protocol for constructing FoMV VIGS clones and inoculating them into maize seedlings. PMID- 28986906 TI - Selective Knockdowns in Maize by Sequence-Specific Protein Aggregation. AB - Protein aggregation is determined by 5-15 amino acids peptides of the target protein sequence, so-called aggregation-prone regions (APRs) that specifically self-associate to form beta-structured inclusions. The presence of APRs in a target protein can be predicted by a dedicated algorithm, such as TANGO. Synthetic aggregation-prone proteins are designed by expressing specific APRs fused to a fluorescent carrier for stability and visualization. Previously, the stable expression of these proteins in Zea mays (maize) has been demonstrated to induce aggregation of target proteins with specific localization, such as the starch-degrading enzyme alpha-glucan water dikinase, giving rise to plants displaying knockdown phenotypes. Here, we describe how to design synthetic aggregation-prone proteins to harness the sequence specificity of APRs to generate aggregation-associated phenotypes in a targeted manner and in different subcellular compartments. This method points toward the application of induced targeted aggregation as a useful tool to knock down protein functions in maize and to generate crops with improved traits. PMID- 28986908 TI - Use of a Virus Gene Silencing Vector for Maize Functional Genomics Research. AB - Virus-induced gene silencing (VIGS) is a genetic technology that exploits the RNA mediated defense against virus. The method has great potential for plant reverse genetics as it could knock down gene expression in a rapid way, which is triggered by a replicating viral genome engineered to carry a fragment of host gene to be silenced. A number of efficient VIGS vectors are available for dicots, such as for model plant Nicotiana benthamiana; however, only a few of VIGS vectors for monocotyledonous cereal crops. Here, we describe the method for the use of a newly developed VIGS vector based on a maize-infecting Cucumber mosaic virus (CMV) strain ZMBJ-CMV for maize. The RNA2 of ZMBJ-CMV was modified as a vector pCMV201-2bN81 having multiple cloning sites for the insert of 100-300 bp fragment of target gene. Using a method of vascular puncture inoculation of maize seeds with crude sap prepared from Agrobacterium-infiltrated N. benthamiana leaves, silencing of target genes could be obtained in 4 weeks. PMID- 28986909 TI - Laser-Capture Microdissection of Maize Kernel Compartments for RNA-Seq-Based Expression Analysis. AB - Laser-capture microdissection (LCM) enables isolation of single cells or groups of cells for a variety of downstream applications including transcriptome profiling. Recently, this methodology has found a more widespread use particularly with the advent of next-generation sequencing techniques that enable deep profiling of the limited amounts of RNA obtained from fixed or frozen sections. When used with fixed tissues, a major experimental challenge is to balance the tissue integrity needed for microscopic visualization of the cell types of interest with that of the RNA quality necessary for deep profiling. Complex biological structures such as seeds or kernels pose an especially difficult case in this context as in many instances the key internal structures such as the embryo and the endosperm are relatively inaccessible. Here, we present an optimized LCM protocol for maize kernel that has been developed specifically to enable profiling of the early stages of endosperm development using RNA-Seq. PMID- 28986910 TI - Ribosome Profiling in Maize. AB - Ribosome profiling (also known as Ribo-seq) provides a genome-wide, high resolution, and quantitative accounting of mRNA segments that are occupied by ribosomes in vivo. The method has been used to address numerous questions in bacteria, yeast, and metazoa, but its application to questions in plant biology is just beginning. This chapter provides a detailed protocol for profiling ribosomes in plant leaf tissue. The method was developed and optimized with maize, but it has been used successfully with Arabidopsis and tobacco as well. The method captures ribosome footprints from the chloroplast and cytosol in the same preparation, but it is not optimal for detecting the footprints of mitochondrial ribosomes. The protocol is robust and simpler than many of the methods reported previously for ribosome profiling in plants. PMID- 28986911 TI - Detection of DNA Methylation by Whole-Genome Bisulfite Sequencing. AB - DNA methylation plays an important role in the regulation of the expression of transposons and genes. Various methods have been developed to assay DNA methylation levels. Bisulfite sequencing is considered to be the "gold standard" for single-base resolution measurement of DNA methylation levels. Coupled with next-generation sequencing, whole-genome bisulfite sequencing (WGBS) allows DNA methylation to be evaluated at a genome-wide scale. Here, we described a protocol for WGBS in plant species with large genomes. This protocol has been successfully applied to assay genome-wide DNA methylation levels in maize and barley. This protocol has also been successfully coupled with sequence capture technology to assay DNA methylation levels in a targeted set of genomic regions. PMID- 28986912 TI - Plant Gene Regulation Using Multiplex CRISPR-dCas9 Artificial Transcription Factors. AB - Besides genome editing, the CRISPR-Cas9-based platform provides a new way of engineering artificial transcription factors (ATFs). Multiplex of guide RNA (gRNA) expression cassettes holds a great promise for many useful applications of CRISPR-Cas9. In this chapter, we provide a detailed protocol for building advanced multiplexed CRISPR-dCas9-Activator/repressor T-DNA vectors for carrying out transcriptional activation or repression experiments in plants. We specifically describe the assembly of multiplex T-DNA vectors that can express multiple gRNAs to activate a silenced gene, or to repress two independent miRNA genes simultaneously in Arabidopsis. We then describe a "higher-order" vector assembly method for increased multiplexing capacity. This higher-order assembly method in principle allows swift stacking of gRNAs cassettes that are only limited by the loading capacity of a cloning or expression vector. PMID- 28986913 TI - Cellular and Subcellular Level Localization of Maize Lipids and Metabolites Using High-Spatial Resolution MALDI Mass Spectrometry Imaging. AB - Recent technological advances have pushed the achievable spatial resolution for mass spectrometry imaging (MSI) to cellular and subcellular levels. Direct visualization of maize tissues by this tool has provided key insights into the localization of metabolites and lipids. This chapter outlines methodology for sample preparation, data acquisition, and data analysis of maize tissue sections using high-spatial resolution matrix-assisted laser desorption ionization (MALDI) MSI, as well as the incorporation of a multi-resolution optical system, which allows for simple inter-conversion between different resolution setups (5, 10, and 50 MUm imaging). PMID- 28986914 TI - Reflections on 50 Years of the Journal of the History of Biology. PMID- 28986915 TI - Globalizing Genomics: The Origins of the International Nucleotide Sequence Database Collaboration. AB - Genomics is increasingly considered a global enterprise - the fact that biological information can flow rapidly around the planet is taken to be important to what genomics is and what it can achieve. However, the large-scale international circulation of nucleotide sequence information did not begin with the Human Genome Project. Efforts to formalize and institutionalize the circulation of sequence information emerged concurrently with the development of centralized facilities for collecting that information. That is, the very first databases build for collecting and sharing DNA sequence information were, from their outset, international collaborative enterprises. This paper describes the origins of the International Nucleotide Sequence Database Collaboration between GenBank in the United States, the European Molecular Biology Laboratory Databank, and the DNA Database of Japan. The technical and social groundwork for the international exchange of nucleotide sequences created the conditions of possibility for imagining nucleotide sequences (and subsequently genomes) as a "global" objects. The "transnationalism" of nucleotide sequence was critical to their ontology - what DNA sequences came to be during the Human Genome Project was deeply influenced by international exchange. PMID- 28986916 TI - The new frontier of studying human anatomy: Introducing evidence-based anatomy. PMID- 28986917 TI - Optimization of data acquisition in axial CT under the framework of sampling on lattice for suppression of aliasing artifacts with algorithmic detector interlacing. AB - PURPOSE: We present the methodology for analyzing and optimizing the sampling structure of projection data acquisition in axial multidetector CT (MDCT) and cone beam CT (CBCT) under the framework of sampling on lattice. Specifically, we propose and evaluate the scheme of interlaced detector cell binning for suppression of longitudinal aliasing artifacts. In addition, we investigate the proposed scheme's capability of mitigating shift variation in spatial resolution and possibility of improving CB image reconstruction accuracy. METHODS: Under the framework of sampling on lattice, the proposed scheme is evaluated using an axial MDCT with its architecture similar to that of state-of-the-art CT scanners for diagnostic imaging in the clinic. The widely used FDK algorithm is adopted for image reconstruction, in which either horizontal/latitudinal or vertical/longitudinal interpolation is used for lining-up of projection data between interlaced detector cells. Using a spiral clock phantom, the capability of suppressing aliasing artifacts and possibility of improving reconstruction accuracy is quantitatively investigated. The in-plane spatial resolution, as assessed by the modulation transfer function (MTF), and its shift-variant property are quantitatively assessed using wire phantoms, while the through-plane spatial resolution and its shift-variant behavior are assessed by the slice sensitivity profile (SSP) using thin foil phantoms. RESULTS: The preliminary results show that the interlaced detector cell binning can suppress longitudinal aliasing artifacts effectively, while the shift variation in spatial resolution and reconstruction inaccuracy can be mitigated moderately. In addition, the direction, along which the interpolation is carried out to line up projection data between the interlaced detector cells for image reconstruction, plays a significant role in determining the in-plane and through-plane spatial resolution. CONCLUSIONS: The scheme of interlaced detector cell binning with longitudinal interpolation for data lining-up is an effective solution for suppression of longitudinal aliasing artifacts in axial MDCT and CBCT. PMID- 28986918 TI - Spatial features of proteins related to their phosphorylation and associated structural changes. AB - Protein phosphorylation is widely used in biological regulatory processes. The study of spatial features related to phosphorylation sites is necessary to increase the efficacy of recognition of phosphorylation patterns in protein sequences. Using the data on phosphosites found in amino acid sequences, we mapped these sites onto 3D structures and studied the structural variability of the same sites in different PDB entries related to the same proteins. Solvent accessibility was calculated for the residues known to be phosphorylated. A significant change in accessibility was shown for many sites, but several ones were determined as buried in all the structures considered. Most phosphosites were found in coil regions. However, a significant portion was located in the structurally stable ordered regions. Comparison of structures with the same sites in modified and unmodified states showed that the region surrounding a site could be significantly shifted due to phosphorylation. Comparison between non-modified structures (as well as between the modified ones) suggested that phosphorylation stabilizes one of the possible conformations. The local structure around the site could be changed due to phosphorylation, but often the initial conformation of the site surrounding is not altered within bounds of a rather large substructure. In this case, we can observe an extensive displacement within a protein domain. Phosphorylation without structural alteration seems to provide the interface for domain-domain or protein-protein interactions. Accounting for structural features is important for revealing more specific patterns of phosphorylation. It is also necessary for explaining structural changes as a basis for regulatory processes. PMID- 28986919 TI - Mepolizumab-a novel option for the treatment of hypereosinophilic syndrome in childhood. AB - BACKGROUND: Mepolizumab was originally intended as a therapeutic agent for atopic asthma in adults, and consequently, little is known about its use in children. Up to now, corticosteroids have formed the basis of the initial treatment of hypereosinophilic syndromes and are shown to be effective in most patients. To analyze the effect of mepolizumab in children is the aim of this study. METHODS: We are reporting the experience of the effect of mepolizumab in 2 pediatric patients with hypereosinophilic syndrome that was not sufficiently controlled by other drugs. In addition, the literature regarding the treatment with mepolizumab in pediatric and adult patients is reviewed for the most important studies regarding safety and efficacy. RESULTS: Mepolizumab therapy showed in 2 pediatric patients with severe hypereosinophilic syndrome a safe and efficient therapeutic approach. No significant intolerances appeared. Furthermore, treatment with systemic corticosteroids was terminated, and therefore, severe side effects were avoided in our pediatric cases. CONCLUSIONS: Anti-IL-5 antibodies, which can be applied without substantial drug intolerances, are a new, safe, and effective treatment option for pediatric patients with hypereosinophilic syndrome. PMID- 28986920 TI - Meta-analysis of the effectiveness of nursing discharge planning interventions for older inpatients discharged home. AB - AIM: To determine the effectiveness of nursing discharge planning interventions on health-related outcomes for older inpatients discharged home. BACKGROUND: Inadequate discharge planning for the ageing population poses significant challenges for health services. Effective discharge planning interventions have been examined in several studies, but little information is available on nursing interventions for older people. Despite the research published on the importance of discharge planning, the impact on patient's health outcomes still needs to be evaluated in practice. DESIGN: Systematic review and meta-analysis. DATA SOURCES: A systematic search was undertaken across 13 databases to retrieve published and unpublished studies in English between 2000-2015. REVIEW METHODS: Critical appraisal, data extraction and meta-analysis followed the methodology of the Joanna Briggs Institute. RESULTS: Thirteen studies were included in the review, 2 of 13 were pilot studies and one had a pre-post design. Included studies involved 3,964 participants with a median age of 77 years. Nurse discharge planning did not significantly reduce hospital readmission or quality of life, except readmission was lower across studies conducted in the USA. The overall effect score for nurse discharge planning on length of stay was statistically significant and positive. CONCLUSION: Nursing discharge planning is a complex intervention and difficult to evaluate. Findings suggest that nursing discharge planning for older inpatients discharged home increases the length of stay yet neither reduces readmission rate nor improves quality of life. PMID- 28986921 TI - Amino acid profiles of rumen undegradable protein: a comparison between forages including cereal straws and alfalfa and their respective total mixed rations. AB - Optimizing the amino acid (AA) profile of rumen undegradable protein (RUP) can positively affect the amount of milk protein. This study was conducted to improve knowledge regarding the AA profile of rumen undegradable protein from corn stover, rice straw and alfalfa hay as well as the total mixed ratio diets (TMR) based on one of them as forage source [forage-to-concentrate ratio of 45:55 (30% of corn stover (CS), 30% of rice straw (RS), 23% of alfalfa hay (AH) and dry matter basis)]. The other ingredients in the three TMR diets were similar. The RUP of all the forages and diets was estimated by incubation for 16 hr in the rumen of three ruminally cannulated lactating cows. All residues were corrected for microbial colonization, which was necessary in determining the AA composition of RUP from feed samples using in situ method. Compared with their original AA composition, the AA pattern of forages and forage-based diets changed drastically after rumen exposure. In addition, the extent of ruminal degradation of analysed AA was not constant among the forages. The greatest individual AA degradability of alfalfa hay and corn stover was Pro, but was His of rice straw. A remarkable difference was observed between microbial attachment corrected and uncorrected AA profiles of RUP, except for alfalfa hay and His in the three forages and TMR diets. The ruminal AA degradability of cereal straws was altered compared with alfalfa hay but not for the TMR diets. In summary, the AA composition of forages and TMR-based diets changed significantly after ruminal exposure, indicating that the original AA profiles of the feed cannot represent its AA composition of RUP. The AA profile of RUP and ruminal AA degradability for corn stover and rice straw contributed to missing information in the field. PMID- 28986922 TI - Estimation of lysine requirements for growing Japanese quails. AB - This study was conducted to estimate the lysine requirements of growing meat-type Japanese quails based on different growth responses using different regression models. Experimental treatments including five doses of dietary lysine (9.40, 10.9, 12.4, 13.9 and 15.4 g/kg of diet) were used in a dose-response platform from 7 to 21 day of age. A total of 375, 7-day old quail chicks were randomly allotted to one of five dietary treatments with five replicate pens and 15 birds per pen. Performance traits including feed intake (FI), weight gain (G) and feed:gain (F:G) and carcass criteria including dressing (DRS), breast meat yield (BMY) and leg meat yield (LMY) were measured and used to fit several models (e.g., spline and quadratic polynomial models). Except FI and LMY, other parameters responded to dietary treatments (p < .05), in which G linearly but F:G, DRS and BMY quadratically responded to incremental levels of lysine (p < .05). On the basis of statistical merit, the best estimation of lysine requirements for G, F:G, BMY and DRS was 12.39 (R2 : .93 and Sy.x : 2.35), 12.40 (R2 : .98 and Sy.x : 0.001), 13.64 (R2 : .99 and Sy.x : 0.15) and 13.80 (R2 : .99 and Sy.x : 0.50) g/kg of diet respectively. This study showed that lysine requirements for maximum carcass yield and its attributes (e.g., BMY) might be higher than those needed for maximum growth rate or feed efficiency. PMID- 28986923 TI - Crystal structure of D-glycero-Beta-D-manno-heptose-1-phosphate adenylyltransferase from Burkholderia pseudomallei. AB - The crystal structure of HldC from B. pseudomallei (BpHldC), the fourth enzyme of the heptose biosynthesis pathway, has been determined. BpHldC converts ATP and d glycero-beta-d-manno-heptose-1-phosphate into ADP-d-glycero-beta-d-manno-heptose and pyrophosphate. The crystal structure of BpHldC belongs to the nucleotidyltransferase alpha/beta phosphodiesterase superfamily sharing a common Rossmann-like alpha/beta fold with a conserved T/HXGH sequence motif. The invariant catalytic key residues of BpHldC indicate that the core catalytic mechanism of BpHldC may be similar to that of other closest homologues. Intriguingly, a reorientation of the C-terminal helix seems to guide open and close states of the active site for the catalytic reaction. PMID- 28986924 TI - Physician's appraisal vs documented signs and symptoms in the interpretation of food challenge tests: The EuroPrevall birth cohort. AB - BACKGROUND: Blinded food challenges are considered the current gold standard for the diagnosis of food allergies. We used data from a pan-European multicenter project to assess differences between study centers, aiming to identify the impact of subjective aspects for the interpretation of oral food challenges. METHODS: Nine study centers of the EuroPrevall birth cohort study about food allergy recruited 12 049 newborns and followed them for up to 30 months in regular intervals. Intensive training was conducted and every center visited to ensure similar handling of the protocols. Suspected food allergy was clinically evaluated by double-blind, placebo-controlled food challenges using a nine dose escalation protocol. The primary challenge outcomes based on physician's appraisal were compared to documented signs and symptoms. RESULTS: Of 839 challenges conducted, study centers confirmed food allergy in 15.6% to 53.6% of locally conducted challenges. Centers reported 0 to 16 positive placebo challenges. Worsening of eczema was the most common sign when challenged with placebo. Agreement between documented objective signs and the challenge outcome assigned by the physician was heterogeneous, with Cohen's kappa spanning from 0.42 to 0.84. CONCLUSIONS: These differences suggest that the comparison of food challenge outcomes between centers is difficult despite common protocols and training. We recommend detailed symptom assessment and documentation as well as objective sign-based challenge outcome algorithms to assure accuracy and comparability of blinded food challenges. Training and supervision of staff conducting food challenges is a mandatory component of reliable outcome data. PMID- 28986925 TI - Cerebral blood flow in normal aging adults: cardiovascular determinants, clinical implications, and aerobic fitness. AB - Senescence is a leading cause of mortality, disability, and non-communicable chronic diseases in older adults. Mounting evidence indicates that the presence of cardiovascular disease and risk factors elevates the incidence of both vascular cognitive impairment and Alzheimer's disease (AD). Age-related declines in cardiovascular function may impair cerebral blood flow (CBF) regulation, leading to the disruption of neuronal micro-environmental homeostasis. The brain is the most metabolically active organ with limited intracellular energy storage and critically depends on CBF to sustain neuronal metabolism. In patients with AD, cerebral hypoperfusion, increased CBF pulsatility, and impaired blood pressure control during orthostatic stress have been reported, indicating exaggerated, age-related decline in both cerebro- and cardiovascular function. Currently, AD lacks effective treatments; therefore, the development of preventive strategy is urgently needed. Regular aerobic exercise improves cardiovascular function, which in turn may lead to a better CBF regulation, thus reducing the dementia risk. In this review, we discuss the effects of aging on cardiovascular regulation of CBF and provide new insights into the vascular mechanisms of cognitive impairment and potential effects of aerobic exercise training on CBF regulation. This article is part of the Special Issue "Vascular Dementia". PMID- 28986926 TI - ADAM8 expression in breast cancer derived brain metastases: Functional implications on MMP-9 expression and transendothelial migration in breast cancer cells. AB - Metastatic breast cancer affects long-term survival and is a major cause of cancer death for women worldwide. The Metalloprotease-Disintegrin ADAM8 promotes breast cancer development and brain metastasis in a mouse breast cancer model. Here, abundant ADAM8 expression was detected in primary human breast tumors and associated brain metastases. To investigate the function of ADAM8 in metastasis, MB-231 breast cancer cells with ADAM8 knockdown (MB-231_shA8) and scramble control cells (MB-231_shCtrl) were analyzed for their capability to develop metastases. In vitro, formation of metastatic complexes in hanging drops is dependent on ADAM8 and blocked by ADAM8 inhibition. MB-231_shA8 in contrast to MB 231_shCtrl cells were impaired in transmigration through an endothelial and a reconstituted blood-brain barrier. Out of 23 MMP and 22 ADAM genes, only the MMP 9 gene was affected by ADAM8 knockdown in MB-231_shA8 cells. Following re expression of wild-type ADAM8 in contrast to ADAM8 lacking the cytoplasmic domain in MB-231_shA8 cells caused increased levels of activated pERK1/2 and pCREB (S133) that were associated with elevated MMP-9 transcription. Application of ADAM8 and MMP-9 antibodies reduced transmigration of MB-231 cells suggesting that ADAM8 affects transmigration of breast cancer cells by MMP-9 regulation. ADAM8 dependent transmigration was confirmed in Hs578t cells overexpressing ADAM8. Moreover, transmigration of MB-231 and Hs578t cells was significantly reduced for cells treated with an antibody directed against P-selectin glycoprotein ligand (PSGL-1), a substrate of ADAM8. From these data we conclude that ADAM8 promotes early metastatic processes such as transendothelial migration by upregulation of MMP-9 and shedding of PSGL-1 from breast cancer cells. PMID- 28986927 TI - Effects of phyto-oestrogen quercetin on productive performance, hormones, reproductive organs and apoptotic genes in laying hens. AB - Quercetin, a polyphenolic flavonoid with diverse biological activities including anti-inflammatory and antiviral, inhibits lipid peroxidation, prevents oxidative injury and cell death. The purpose of the research was to investigate the effect of quercetin on productive performance, reproductive organs, hormones and apoptotic genes in laying hens between 37 and 45 weeks of age, because of the structure and oestrogenic activities similar to 17beta-oestradiol. The trial was conducted using 240 Hessian laying hens (37 weeks old), housed in wire cages with two hens in each cage. These hens were randomly allotted to four treatments with six replicates, 10 hens in each replicate and fed with diets containing quercetin as 0, 0.2, 0.4 and 0.6 g/kg feed for 8 weeks. The results showed that dietary quercetin significantly increased (p < .05) the laying rate and was higher in group supplemented with 0.4 g/kg, and feed-egg ratio was decreased (p < .05) by quercetin. Dietary quercetin has no effect (p > .05) on average egg weight and average daily feed intake. Compared with control, secretion of hormones, oestradiol (E2 ), progesterone (P4), follicle-stimulating hormone (FSH), luteinizing hormone (LH), insulin-like growth factors-1 (IGF-1) and growth hormone (GH), was found to be significantly higher (p < .05) in quercetin supplemented groups. Also ovary index, uterus index and oviduct index were not significantly influenced (p > .05) by quercetin, whereas magnum index, isthmus index, magnum length, isthmus length and follicle numbers were significantly increased (p < .05) with quercetin supplementation. Additionally, expression of apoptotic genes was significantly (p < .05) up-regulated or down-regulated by quercetin. These results indicated that quercetin improved productive performance, and its mechanism may be due to the oestrogen-like activities of quercetin. PMID- 28986928 TI - A systematic review of characteristics of couple-based intervention studies addressing sexuality following cancer. AB - AIM: To describe the characteristics of couple-based intervention studies that address sexuality following cancer. BACKGROUND: Sexuality-related problems are common among cancer survivors and their partners. DESIGN: Systematic literature review with a narrative summary of results. DATA SOURCES: Electronic searches were conducted in PubMed, CINAHL and PsychINFO. We included studies published from 1 January 2009 - 31 December 2016. Additional information was retrieved by scrutinizing reference lists, conducting citation tracking and contacting authors. We included all types of quantitative intervention studies published in the English language which contained outcome measures corresponding to the neo theoretical framework of sexuality-sexual function, sexual relationship and sexual self-concept. REVIEW METHODS: Our review was guided by the Joanna Briggs Institute reviewer's manual. Data were extracted and appraised using the standardized checklists for quantitative studies. This assessment was conducted independently by two reviewers. A third reviewer was involved if consensus could not be reached. RESULTS: Fourteen studies were included. Interventions were delivered face-to-face, by telephone or via the Internet. Sessions ranged from 1 8, with a duration from 2-22 weeks. Most studies offered >=3 sessions. Interventions addressed unique concerns and/or provided general education. There was little agreement on the use of outcome measures. Most studies inadequately described fidelity to the study protocol and the training of interventionists. CONCLUSION: There was no clear consensus about how couple-based interventions are best structured. The results provide tentative evidence for how the quality of future research studies can be improved and how knowledge can be used in clinical practice. PMID- 28986929 TI - Evolution of brain region volumes during artificial selection for relative brain size. AB - The vertebrate brain shows an extremely conserved layout across taxa. Still, the relative sizes of separate brain regions vary markedly between species. One interesting pattern is that larger brains seem associated with increased relative sizes only of certain brain regions, for instance telencephalon and cerebellum. Till now, the evolutionary association between separate brain regions and overall brain size is based on comparative evidence and remains experimentally untested. Here, we test the evolutionary response of brain regions to directional selection on brain size in guppies (Poecilia reticulata) selected for large and small relative brain size. In these animals, artificial selection led to a fast response in relative brain size, while body size remained unchanged. We use microcomputer tomography to investigate how the volumes of 11 main brain regions respond to selection for larger versus smaller brains. We found no differences in relative brain region volumes between large- and small-brained animals and only minor sex-specific variation. Also, selection did not change allometric scaling between brain and brain region sizes. Our results suggest that brain regions respond similarly to strong directional selection on relative brain size, which indicates that brain anatomy variation in contemporary species most likely stem from direct selection on key regions. PMID- 28986930 TI - Write right, quite right: Orthography in Latin Anatomical Terms. AB - Spelling variants are common in Latin anatomical terms. Some of these variants cause confusion with respect to the meaning of the word by altering the base of the word to resemble a different word base. Thus these variants should be considered errors, comparable to errors in declension of nouns and adjectives, and errors in the formation of neologisms. Use of correct Latin words in Latin anatomical terms should increase the rigor, stability, and universality of the nomenclature. Clin. Anat. 31:77-80, 2018. (c) 2017 Wiley Periodicals, Inc. PMID- 28986931 TI - Can point-of-care ultrasound predict spinal hypotension during caesarean section? A prospective observational study. AB - Spinal anaesthesia for elective caesarean section is associated with maternal hypotension, secondary to alteration of sympathetic tone and hypovolemia, in up to 70% of cases. Measurement of the subaortic variation in the velocity time integral (VTI) after passive leg raising allows prediction of fluid responsiveness. Our objective, in this prospective single-centre observational study, was to assess the ability of change in VTI after 45 degrees passive leg raising to predict hypotension after spinal anaesthesia. Ultrasound measurements were performed just before elective caesarean section. Anaesthesia, intravenous coloading and prophylactic vasopressor treatment were standardised according to current guidelines. We studied 40 women. Hypotension occurred in 17 (45%) women. The area (95%CI) under the receiver operating characteristics (ROC) curve for the prediction of spinal hypotension was 0.8 (0.6-0.9; p = 0.0001). Seventeen women had a change in VTI with leg elevation <= 8%, which was predictive for not developing hypotension, and 11 had a change >= 21%, predictive for hypotension. The grey zone between 8% and 21%, with inconclusive values, included 12 women. We suggest that cardiac ultrasound provides characterisation of the risk of hypotension following spinal anaesthesia at elective caesarean section, and therefore may allow individualised strategies for prevention and management. PMID- 28986932 TI - Usefulness of water immersion observations to identify the stigmata of hemorrhage in colonic diverticular bleeding. PMID- 28986933 TI - Liquid tissue surrogates for X-ray and CT phantom studies. AB - PURPOSE: To develop a simple method for producing liquid-tissue-surrogate (LTS) materials that accurately represent human soft tissues in terms of density and X ray attenuation coefficient. METHODS AND MATERIALS: We evaluated hypothetical mixtures of water, glycerol, butanol, methanol, sodium chloride, and potassium nitrate; these mixtures were intended to emulate human adipose, blood, brain, kidney, liver, muscle, pancreas, and skin. We compared the hypothetical densities, effective atomic numbers (Zeff ), and calculated discrete-energy CT attenuation [Hounsfield Units (HU)] of the proposed materials with those of human tissue elemental composition as specified in International Commission on Radiation Units (ICRU) Report 46. We then physically produced the proposed LTS materials for adipose, liver, and pancreas tissue, and we measured the polyenergetic CT attenuation (also expressed as HU) of these materials within a 32 cm phantom using a 64-slice clinical CT scanner at 80 kVp, 100 kVp, 120 kVp, and 140 kVp. RESULTS: The predicted densities, Zeff , and calculated discrete energy CT attenuation of our proposed formulations generally agreed with those of ICRU within < 1% or < 10 HU. For example, the densities of our hypothetical materials agreed precisely with ICRU's reported values and were 0.95 g/mL for adipose tissue, 1.04 g/mL for pancreatic tissue, and 1.06 g/mL for liver tissue; the discrete-energy CT attenuation at 60 keV of our hypothetical materials (and ICRU-specified compositions) were -107 HU (-113 HU) for adipose #3, -89 HU (-90 HU) for adipose #2, 56 HU (55 HU) for liver tissue, and 31 HU (31 HU) for pancreatic tissue. The densities of our physically produced materials (compared to ICRU-specified compositions) were 0.947 g/mL (0.0%) for adipose #2, 1.061 g/mL (+2.0%) for pancreatic tissue, and 1.074 g/mL (+1.3%) for liver tissue. The empirical polyenergetic CT attenuation measurements of our LTS materials (and the discrete-energy HU of the ICRU compositions at the mean energy of each spectrum) at 80 kVp were -104 HU (-113 HU) for adipose #3, -87 HU (-90 HU) for adipose #2, 59 HU (55 HU) for liver tissue, and 33 HU (31 HU) for pancreatic tissue; at 120 kVp, these were -83 HU (-83 HU) for adipose #3, -68 HU (-63 HU) for adipose #2, 55 HU (52 HU) for liver tissue, and 35 HU (33 HU) for pancreatic tissue. CONCLUSION: Our method for formulating tissue surrogates allowed straightforward production of solutions with CT attenuation that closely matched the target tissues' expected CT attenuation values and trends with kVp. The LTSs' inexpensive and widely available constituent chemicals, combined with their liquid state, should enable rapid production and versatile use among different phantom and experiment types. Further study is warranted, such as the inclusion of contrast agents. These liquid tissue surrogates may potentially accelerate development and testing of advanced CT imaging techniques and technologies. PMID- 28986935 TI - Diagnosis and management of diaper dermatitis in infants with emphasis on skin microbiota in the diaper area. AB - Diaper dermatitis is the most common inflammatory skin eruption within the diaper area in infants and toddlers. Although it rarely causes problems for prolonged periods of time, it causes considerable distress for both infants and parents. Diapered skin is exposed to friction, excessive hydration, varying pH, and is in constant contact with urine and feces, both of which are highly irritant to the skin. The three most common types of diaper dermatitis include chaffing dermatitis, irritant contact dermatitis, and diaper candidiasis. However, a variety of other skin conditions may manifest in the diaper area. Candida albicans and Staphylococcus aureus are most frequently isolated from the affected area and are thought to have a predominant role in diaper dermatitis. The review includes an overview of the epidemiology, etiology, and common skin microbiota in the diaper area. State-of-the-art strategies for diagnosis, management, and prevention of diaper dermatitis are also included. Appropriate skin care can help in the prevention of diaper dermatitis and can aid the reparation of the skin. This review discusses common causes, skin microbiota within the diapered area, differential diagnosis, and finally possible prevention and treatment recommendations. Recent findings have proven that the key to efficient eradication of irritant diaper dermatitis lies in its prevention. PMID- 28986934 TI - Mechanistic Model-Informed Proarrhythmic Risk Assessment of Drugs: Review of the "CiPA" Initiative and Design of a Prospective Clinical Validation Study. AB - The Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative is developing and validating a mechanistic-based assessment of the proarrhythmic risk of drugs. CiPA proposes to assess a drug's effect on multiple ion channels and integrate the effects in a computer model of the human cardiomyocyte to predict proarrhythmic risk. Unanticipated or missed effects will be assessed with human stem cell-derived cardiomyocytes and electrocardiogram (ECG) analysis in early phase I clinical trials. This article provides an overview of CiPA and the rationale and design of the CiPA phase I ECG validation clinical trial, which involves assessing an additional ECG biomarker (J-Tpeak) for QT prolonging drugs. If successful, CiPA will 1) create a pathway for drugs with hERG block / QT prolongation to advance without intensive ECG monitoring in phase III trials if they have low proarrhythmic risk; and 2) enable updating drug labels to be more informative about proarrhythmic risk, not just QT prolongation. PMID- 28986936 TI - In ovo feeding of creatine pyruvate modulates growth performance, energy reserves and mRNA expression levels of gluconeogenesis and glycogenesis enzymes in liver of embryos and neonatal broilers. AB - The effects of in ovo feeding (IOF) of creatine pyruvate (CrPyr) on the growth performance, energy reserves and mRNA expression levels of gluconeogenesis and glycogenesis enzymes in liver of late-term embryos and neonatal broilers were investigated. After candling on 16 day of incubation, a total of 960 eggs were randomly assigned to three treatments: (i) non-injected control, (ii) saline group injected with 0.6 ml of 0.75% physiological saline and (iii) Creatine pyruvate group injected with 0.6 ml of physiological saline containing 12 mg CrPyr/egg. After hatching, 120 male chicks with average body weight (BW) were randomly allocated into each treatment group for a 7-day feeding trial. The results showed that broilers subjected to CrPyr treatment had higher BW than those of the control and saline groups on 1, 3 and 7 day post-hatch, as well as the yolk sac weight on 19 day of incubation (19 E), the day of hatch and 3 day post-hatch (p < .05). Compared with the control and saline groups, IOF of CrPyr increased the plasma creatine concentration on the day of hatch, and the plasma pyruvate concentration on the day of hatch and 3 day post-hatch (p < .05). Moreover, IOF of CrPyr increased the liver pyruvate and glucose concentrations on 19 E and the day of hatch, and the liver glycogen concentration during the experiment (p < .05). Broilers in the CrPyr group showed increased mRNA expression levels of pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PEPCK) and glycogen synthase 2 (GYS2) on 19 E and the day of hatch (p < .05). These results indicated that IOF of CrPyr increased energy reserves in liver of embryos and neonatal broilers possibly through upregulating the mRNA expression levels of PC, PEPCK and GYS2, which could benefit the increase of BW in broilers on 7 day post-hatch. PMID- 28986937 TI - Effects of Chinese herbal medicine and cold exposure on plasma glucose, leucine and energy metabolism in sheep. AB - An experiment was carried out to assess the feeding effect of Chinese herbal medicine on N balance, ruminal fermentation characteristics, kinetics of plasma glucose, leucine and energy metabolism in sheep kept at thermoneutral environment (23 degrees C) or exposed to cold (2-4 degrees C). Four sheep were subjected to either mixed hay (MH-diet) or hay supplemented with 2% of a traditional nourishing Chinese herbal medicine mixture (Astragalus root, Angelica root and Atractylodes rhizome; CHM-diet) over two 23-day periods using a crossover design. Cold exposure was conducted for 5 days. The isotope dilution of [U-13 C]glucose with open circuit calorimetry was used to determine the turnover and oxidation rates of plasma glucose and metabolic heat production. The rate of plasma leucine turnover was measured with an isotope dilution method using [1-13 C]leucine. N intake was higher, N excretion through faeces was lower and N digestibility was higher for the CHM-diet than the MH-diet. Rumen pH was lower, concentration of rumen NH3 was higher, concentrations of rumen total VFA and acetate tended to be higher and propionate was higher for the CHM-diet compared with the MH-diet. Turnover rate of plasma glucose was higher for the CHM-diet than the MH-diet and increased during cold exposure. Oxidation rate of plasma glucose did not differ between diets and also between environments. Turnover rate of plasma leucine was higher for the CHM-diet compared with the MH-diet but remained similar between environments. Heat production was greater for the CHM-diet than the MH-diet and increased during cold exposure. No significant diet * environment interaction was detected. The present results demonstrated that plasma glucose and energy metabolism were enhanced by both Chinese herbal medicine and cold exposure; plasma leucine metabolism was enhanced by Chinese herbal medicine but with lack of change in response to cold exposure in sheep under the conditions of the current experiment. PMID- 28986938 TI - Rational Inference of Beliefs and Desires From Emotional Expressions. AB - We investigated people's ability to infer others' mental states from their emotional reactions, manipulating whether agents wanted, expected, and caused an outcome. Participants recovered agents' desires throughout. When the agent observed, but did not cause the outcome, participants' ability to recover the agent's beliefs depended on the evidence they got (i.e., her reaction only to the actual outcome or to both the expected and actual outcomes; Experiments 1 and 2). When the agent caused the event, participants' judgments also depended on the probability of the action (Experiments 3 and 4); when actions were improbable given the mental states, people failed to recover the agent's beliefs even when they saw her react to both the anticipated and actual outcomes. A Bayesian model captured human performance throughout (rs >= .95), consistent with the proposal that people rationally integrate information about others' actions and emotional reactions to infer their unobservable mental states. PMID- 28986939 TI - Leishmania infection in rodents in Greece. AB - OBJECTIVE: To investigate the prevalence of Leishmania infection in rodents from various areas of northern Greece. METHODS: Ninety-seven rodents (66 Mus musculus, 19 Rattus norvegicus and 12 R. rattus) were collected during pest control programmes and examined by cytology (spleen and liver smears), serology (ELISA) and PCR (real-time and gel-based) for Leishmania. Date, environment, sex, existence of dogs in the close environment were recorded for each rodent. RESULTS: All cytological preparations were negative, whereas specific IgG was detected in 54.5% in total; 70% of R. norvegicus; 50% of R. rattus; and 50% of M. musculus. In at least one molecular method, 19.6% of the samples in total were positive: 25% of R. rattus, 24% of M. musculus, but no R. norvegicus was found positive. Environment (semi-urban areas, P = 0.037) and species (M. musculus, P = 0.032) were associated with positive PCR. All infected animals showed evidence of low parasite burden, demonstrated by the negative cytological examinations and the high Ct values observed in real-time PCR. CONCLUSION: Due to the proximity of rodents to humans and dogs, these animals may be important in the epidemiology of leishmaniosis, especially if proven that they can infect sand flies. PMID- 28986940 TI - Evaluation of a novel poly(amidoamine) with pendant aminobutyl group on the cellular properties of transfected bone marrow mesenchymal stem cells. AB - Stem cell-based gene therapy has been considered in the treatment of many degenerative diseases. Gene-modified stem cells should maintain its reproductive activity without losing stem cell properties, including genetic phenotype and differentiation potential. In the study, a novel poly (amidoamine) with pendant aminobutyl group (PAA-BA) designed by our group was used in the transfection of bone marrow mesenchymal stromal cells (BMSCs) and the cellular properties post transfection were evaluated, including DNA content, colony forming capacity, genetic phenotype, and multi-directional differentiation. Two classical non-viral gene delivery vectors, polyethylenimine (PEI) and Lipofectamine 2000 (LP2000) were also used. Compared to non-transfected group, PAA-BA showed minor decreased DNA content but maintained BMSCs' phenotype, reproductive activity and multi differentiation potential (osteogenic, chondrogenic, adipogenic, and neurogenic differentiation). Both PAA-BA and PEI transfected BMSCs demonstrated improved osteogenic differentiation ability at late stage but suppressed adipogenic as well as mature neural differentiation in vitro. LP2000 and PEI transfected BMSCs displayed significantly lower DNA content and reproductive activity. These findings suggest that PAA-BA is one of safe gene delivery vectors in BMSCs transfection and plays a role in stem cell's osteogenic and neurogenic differentiation. This study proposes the potential application of PAA-BA in BMSCs based gene therapy, in particular bone and nerve relative diseases. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 686-697, 2018. PMID- 28986941 TI - Electron Bifurcation Makes the Puzzle Pieces Fall Energetically into Place in Methanogenic Energy Conservation. AB - Elaborate arrays of iron-sulfur clusters link active sites via a flavin that bifurcates electrons through two energetically independent paths. The structure of the heterodisulfide reductase provides insight into how methanogens conserve energy through coupling hydrogen oxidation to coordinated exergonic heterodisulfide and endergonic ferredoxin reduction in an overall thermodynamically favorable reaction. PMID- 28986942 TI - Management of behavioural and psychological symptoms of dementia by an aroma massage with acupressure treatment protocol: A randomised clinical trial. AB - AIMS AND OBJECTIVES: This study evaluates the clinical effectiveness of a multicomponent aroma-massage with an acupressure treatment protocol and compared it to cognitive training for the management of behavioural and psychological symptoms of dementia. BACKGROUND: Pharmacological interventions have been unsatisfactory in managing behavioural and psychological symptoms of dementia; thus, complementary and alternative medicine has been extensively researched to identify an adjunct safe and cost-effective intervention. DESIGN: This randomised clinical trial utilised a three-arm parallel group design. Cognitive training was used as a conventional intervention to manage behavioural and psychological symptoms of dementia, whereas exercise was considered "treatment as usual" in this study; both were used as comparisons with the experimental protocol. There were three treatment groups: Group 1: aroma-massage with acupressure + exercise, Group 2: cognitive training + exercise and Group 3: aroma-massage with acupressure + cognitive training. METHOD: Sixty older adults were recruited and randomly assigned to the three groups (20 each). Using the 29-item Chinese Version of the Cohen-Mansfield Agitation Inventory, Neuropsychiatric Inventory, Mini-mental State Examination and Barthel Index-20, the outcome measures were assessed at preintervention, postintervention and the 3-month follow-up to assess behaviour, Activities of Daily Living, cognition, and behavioural and psychological symptoms of dementia severity and distress. Multiple comparisons performed through repeated measures were analysed to detect between-group differences and within-subject differences, as well as the interaction effects between groups and times. RESULTS: The Group 1 and 3 participants showed a significant reduction in the severity and distress caused by behavioural and psychological symptoms of dementia, whereas Group 2 did not demonstrate similar effects. CONCLUSIONS: This clinical study suggests that aroma-massage with acupressure is as effective as cognitive training and can enhance cognitive training in reducing the severity and distress of behavioural and psychological symptoms of dementia. RELEVANCE TO CLINICAL PRACTICE: Aroma-massage with acupressure may serve as an adjunct therapy to reduce behavioural and psychological symptoms of dementia. This therapy is safe, cost-effective and can be implemented by caregivers and family members who are not professionally trained. PMID- 28986944 TI - Stillbirth: Balancing patient preferences with clinical evidence. PMID- 28986943 TI - Crystal structure of Mycobacterium tuberculosis VapC20 toxin and its interactions with cognate antitoxin, VapB20, suggest a model for toxin-antitoxin assembly. AB - : VapBCs, virulence-associated proteins, are the most abundant type II toxin antitoxin (TA) systems in prokaryotes. Under normal conditions, toxin and antitoxin interact to form a heterooctameric complex, which upon binding to operator sites, inhibits their own expression. Under stress conditions, the VapB antitoxin is degraded by cellular proteases to release a free VapC toxin, which in turn inhibits cell growth mainly by targeting protein translation. However, the intermediate steps involved in the assembly of the heterooctameric complex have not been resolved. Here, we report a 1.75 A resolution crystal structure of VapC20, a Sarcin-Ricin loop cleaving toxin from type II TA system of Mycobacterium tuberculosis. Using analytical ultracentrifugation (AUC) studies, we show that VapC20 exists as a homodimer in solution. The structural analysis of VapC homologs further suggests that VapCs form homodimers. We demonstrate that VapC20 is an obligate homodimer, and its self-association is critical for its folding and activity. Surface plasmon resonance experiments suggest that VapC20 interacts with its cognate antitoxin VapB20 to form a stable complex with nanomolar affinity. A high association rate coupled with a very slow dissociation rate ensures minimal toxicity under normal growth conditions. AUC studies reveal that VapB20 also exists as a homodimer in solution and further associates with VapC20 dimers to form heterotetramers and heterooctamers in a concentration dependent manner. The results presented here provide valuable insights into the assembly of VapBC family of toxins which is essential for their function and regulation. DATABASE: Structural data are available in the PDB under the accession numbers 5WZF and 5WZ4. PMID- 28986945 TI - Critical comparison of the on-line and off-line molecularly imprinted solid-phase extraction of patulin coupled with liquid chromatography. AB - Reaching trace amounts of mycotoxin contamination requires sensitive and selective analytical tools for their determination. Improving the selectivity of sample pretreatment steps covering new and modern extraction techniques is one way to achieve it. Molecularly imprinted polymers as selective sorbent for extraction undoubtedly meet these criteria. The presented work is focused on the hyphenation of on-line molecularly imprinted solid-phase extraction with a chromatography system using a column-switching approach. Making a critical comparison with a simultaneously developed off-line extraction procedure, evaluation of pros and cons of each method, and determining the reliability of both methods on a real sample analysis were carried out. Both high-performance liquid chromatography methods, using off-line extraction on molecularly imprinted polymer and an on-line column-switching approach, were validated, and the validation results were compared against each other. Although automation leads to significant time savings, fewer human errors, and required no handling of toxic solvents, it reached worse detection limits (15 versus 6 MUg/L), worse recovery values (68.3-123.5 versus 81.2-109.9%), and worse efficiency throughout the entire clean-up process in comparison with the off-line extraction method. The difficulties encountered, the compromises made during the optimization of on-line coupling and their critical evaluation are presented in detail. PMID- 28986946 TI - Effect of decellularized spinal scaffolds on spinal axon regeneration in rats. AB - A series of complex influencing factors lead to failure of neural regeneration after spinal cord injury (SCI). Up to now, there is no robust treatment that can restore the loss of function caused by injury. Because damaged spinal axons do not spontaneously regenerate in their naturally inhibitory microenvironments, biomaterials that induce neural regeneration to appear as attractive treatments to improve the microenvironmental conditions after SCI. In this study, we report the novel use of decellularized (DC) scaffolds to provide contact guidance for axonal regrowth in vivo. The idea is that the scaffolds comprise some cytokines and a physical compartment that may facilitate regeneration. To evaluate the efficacy of scaffolds in supporting neural regeneration after SCI, the scaffold was implanted into an injured spinal cord of the rat. The injured spinal scaffolds showed a significant increase of the expression of GAP43, NF200, and Nestin in the scaffold implant groups compared with controls without the scaffold. In addition, the motor function has a better recovery. Together, these results demonstrate that spinal acellular scaffold is capable of promoting axonal regeneration after SCI and may serve as a potential tool in the treatment of SCI. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 698-705, 2018. PMID- 28986948 TI - The role of the blood-brain barrier in hypertension. AB - NEW FINDINGS: What is the topic of this review? This review highlights the importance of the blood-brain barrier in the context of diseases involving autonomic dysfunction, such as hypertension and heart failure. What advances does it highlight? It highlights the potential role of pro-inflammatory cytokines, leucocytes and angiotensin II in disrupting the blood-brain barrier in cardiovascular diseases. Advances are highlighted in our understanding of neurovascular unit cells, astrocytes and microglia, with a specific emphasis on their pathogenic roles within the brain. The blood-brain barrier (BBB) is a crucial barrier that provides both metabolic and physical protection to an immune privileged CNS. The BBB has been shown to be disrupted in hypertension. This review addresses the importance of the BBB in maintaining homeostasis in the context of diseases related to autonomic dysfunction, such as hypertension. We highlight the potentially important roles of the immune system and neurovascular unit in the maintenance of the BBB, whereby dysregulation may lead to autonomic dysfunction in diseases such as heart failure and hypertension. Circulating leucocytes and factors such as angiotensin II and pro-inflammatory cytokines are thought ultimately to downregulate endothelial tight junction proteins that are a crucial component of the BBB. The specific mechanisms underlying BBB disruption and their role in contributing to autonomic dysfunction are not yet fully understood but are a growing area of interest. A greater understanding of these systems and advances in our knowledge of the molecular mechanisms causing BBB disruption will allow for the development of future therapeutic interventions in the treatment of autonomic imbalance associated with diseases such as heart failure and hypertension. PMID- 28986947 TI - In vivo diabetic wound healing with nanofibrous scaffolds modified with gentamicin and recombinant human epidermal growth factor. AB - Diabetic wounds are susceptible to microbial infection. The treatment of these wounds requires a higher payload of growth factors. With this in mind, the strategy for this study was to utilize a novel payload comprising of Eudragit RL/RS 100 nanofibers carrying the bacterial inhibitor gentamicin sulfate (GS) in concert with recombinant human epidermal growth factor (rhEGF); an accelerator of wound healing. GS containing Eudragit was electrospun to yield nanofiber scaffolds, which were further modified by covalent immobilization of rhEGF to their surface. This novel fabricated nanoscaffold was characterized using scanning electron microscopy, Fourier transform infrared spectroscopy, and X-ray diffraction. The thermal behavior of the nanoscaffold was determined using thermogravimetric analysis and differential scanning calorimetry. In the in vitro antibacterial assays, the nanoscaffolds exhibited comparable antibacterial activity to pure gentemicin powder. In vivo work using female C57/BL6 mice, the nanoscaffolds induced faster wound healing activity in dorsal wounds compared to the control. The paradigm in this study presents a robust in vivo model to enhance the applicability of drug delivery systems in wound healing applications. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 641-651, 2018. PMID- 28986949 TI - The relationship between HIV and fertility in the era of antiretroviral therapy in sub-Saharan Africa: evidence from 49 Demographic and Health Surveys. AB - OBJECTIVES: To describe regional differences in the relative fertility of HIV positive vs. HIV-negative women and changes as antiretroviral treatment (ART) is scaled up, to improve estimates of predicted need for and coverage of prevention of mother-to-child transmission services at national and subnational levels. METHODS: We analysed 49 nationally representative household surveys in sub Saharan Africa between 2003 and 2016 to estimate fertility rate ratios of HIV positive and HIV-negative women by age using exponential regression and test for regional and urban/rural differences. We estimated the association between national ART coverage and the relationship between HIV and fertility. RESULTS: Significant regional differences exist in HIV and fertility relationships, with less HIV-associated subfertility in Southern Africa. Age patterns of relative fertility are similar. HIV impact on fertility is weaker in urban than rural areas. For women below age 30, regional and urban/rural differences are largely explained by differences in age at sexual debut. Higher levels of national ART coverage were associated with slight attenuation of the relationship between HIV and fertility. CONCLUSIONS: Regional differences in HIV-associated subfertility and urban-rural differences in age patterns of relative fertility should be accounted for when predicting need for and coverage of PMTCT services at national and subnational level. Although HIV impacts on fertility are somewhat reduced at higher levels of national ART coverage, differences in fertility between HIV positive and negative remain, and fertility of women on ART should not be assumed to be the same as HIV-negative women. There were few data in recent years, when ART has reached high levels, and this relationship should continue to be assessed as further evidence becomes available. PMID- 28986950 TI - Modeling of the interaction between osteoblasts and biocompatible substrates as a function of adhesion strength. AB - A goal of current implantology research is to design devices that induce controlled, guided, and rapid healing. Nanoscale structured substrates [e.g., titania nanotubes (TNTs) or carbon nanotubes (CNTs)] dramatically improve the functions of conventional biomaterials. The present investigation evaluated the behavior of osteoblasts cells cultured on smooth and nanostructured substrates, by measuring osteoblasts specific biomarkers [alkaline phosphatase (AP) and total protein] and cells adhesion strength to substrates, followed by semi-empirical modeling to predict the experimental results. Findings were in total agreement with the current state of the art. The proliferation, as well as the AP and total protein levels were higher on the nanostructure phases (TNTs, CNTs) comparing to the smooth ones (plastic and pure titanium). Cells adhesion strength measured was found higher on the nanostructured materials. This coincided with a higher value of proteins which are directly implicated in the process of adherence. Results were accurately predicted through the Viscoelastic Hybrid Interphase Model. A gradual adherence of bone cells to implants using multilayered biomaterials that involve biodegradable polymeric films and a nanoscale modification of titanium surface is suggested to improve performance through an interphase-mediated osteointegration of orthopedic implants. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 621-628, 2018. PMID- 28986952 TI - Effect of Water on the Structure and Stability of Hydrogen-Bonded Oxalic Acid Dimer. AB - As the simplest and most abundant dicarboxylic acid in the atmosphere, oxalic acid (OA) not only plays a key role in aerosol nucleation, but also acts as a prototypical compound for the investigation of intra- and intermolecular hydrogen bonding interactions. A systematic theoretical study on the hydrated OA dimers performed by using DFT at the M06-2X/6-311++G(3df, 2p) level is discussed herein. The properties of hydrogen bonds in clusters are inspected through topological analysis by using atoms in molecules (AIM) theory. The most stable OA dimer involves a cyclic structure with two intermolecular hydrogen bonds. Calculations show that one H2 O has a slight effect on the hydrogen bonds, whereas two water molecules weaken and three water molecules break the two intermolecular hydrogen bonds between OAs. Furthermore, there are no hydrogen-bond interactions between OAs in almost all stable clusters as the number of H2 O molecules increases to four and five. Additionally, ionization and isomerization of OA through water assisted proton-transfer phenomena are observed in tetra- and pentahydrates. This work provides new insights into the conversion of anhydrous OA into hydrated clusters that are helpful for further understanding the atmospheric nucleation process and nature of hydrogen bond. PMID- 28986951 TI - Evolution of precopulatory and post-copulatory strategies of inbreeding avoidance and associated polyandry. AB - Inbreeding depression is widely hypothesized to drive adaptive evolution of precopulatory and post-copulatory mechanisms of inbreeding avoidance, which in turn are hypothesized to affect evolution of polyandry (i.e. female multiple mating). However, surprisingly little theory or modelling critically examines selection for precopulatory or post-copulatory inbreeding avoidance, or both strategies, given evolutionary constraints and direct costs, or examines how evolution of inbreeding avoidance strategies might feed back to affect evolution of polyandry. Selection for post-copulatory inbreeding avoidance, but not for precopulatory inbreeding avoidance, requires polyandry, whereas interactions between precopulatory and post-copulatory inbreeding avoidance might cause functional redundancy (i.e. 'degeneracy') potentially generating complex evolutionary dynamics among inbreeding strategies and polyandry. We used individual-based modelling to quantify evolution of interacting precopulatory and post-copulatory inbreeding avoidance and associated polyandry given strong inbreeding depression and different evolutionary constraints and direct costs. We found that evolution of post-copulatory inbreeding avoidance increased selection for initially rare polyandry and that evolution of a costly inbreeding avoidance strategy became negligible over time given a lower-cost alternative strategy. Further, fixed precopulatory inbreeding avoidance often completely precluded evolution of polyandry and hence post-copulatory inbreeding avoidance, but fixed post-copulatory inbreeding avoidance did not preclude evolution of precopulatory inbreeding avoidance. Evolution of inbreeding avoidance phenotypes and associated polyandry is therefore affected by evolutionary feedbacks and degeneracy. All else being equal, evolution of precopulatory inbreeding avoidance and resulting low polyandry is more likely when post-copulatory inbreeding avoidance is precluded or costly, and evolution of post-copulatory inbreeding avoidance greatly facilitates evolution of costly polyandry. PMID- 28986954 TI - Role of CYP3A in Oral Contraceptives Clearance. PMID- 28986953 TI - CRISPR-Cas9 mediated gene knockout in human coronary artery endothelial cells reveals a pro-inflammatory role of TLR2. AB - Endothelial inflammatory responses promote the development and progression of atherosclerosis. It was reported that Toll-like receptors 2 (TLR2) is associated with endothelial inflammation. However, the effect of TLR2 on inflammatory responses in human coronary artery endothelial cells (HCAECs) remains largely unknown. Here, we tested the hypothesis that TLR2 can enhance inflammatory reactions in HCAECs after stimulated by TLR2 agonist. First, we used CRISPR-Cas9 technology to knockout TLR2 gene in HCAECs. Then, TLR2-KO and wild type HCAECs were treated with TLR2 agonist peptidoglycan (PGN). The expression levels of intercellular cell adhesion molecule-1 (ICAM-1), interleukin-6 (IL-6), and interleukin-8 (IL-8) were analyzed by real-time PCR, Western blot, and ELISA. The expression status of myeloid differentiation primary response gene 88 (MyD88), phosphorylated IRAK-1 (pIRAK-1) and phosphorylated NF-kappaB (pNF-kappaB) were detected by Western blot. Our results show that after treated with TLR2 agonist, the expression levels of ICAM-1, IL-6, and IL-8 were downregulated in TLR2-KO cells compared to those of wild type cells. Further, Western blots of MyD88, pIRAK-1, and pNF-kappaB show that the expression levels of these pro-inflammatory molecules were much lower in TLR2-KO cells compared to that of wild type cells by stimulating with TLR2 agonist. We suggest that TLR2 may affect inflammatory reaction in HCAECs by introducing pro-inflammatory molecules like MyD88, pIRAK-1, and pNF-kappaB. PMID- 28986955 TI - Comparative study of head and neck mucosal melanoma in 66 patients vs 226 patients with cutaneous melanoma: A survival analysis. PMID- 28986956 TI - Decoupling the direct and indirect effects of climate on plant litter decomposition: Accounting for stress-induced modifications in plant chemistry. AB - Decomposition of plant litter is a fundamental ecosystem process that can act as a feedback to climate change by simultaneously influencing both the productivity of ecosystems and the flux of carbon dioxide from the soil. The influence of climate on decomposition from a postsenescence perspective is relatively well known; in particular, climate is known to regulate the rate of litter decomposition via its direct influence on the reaction kinetics and microbial physiology on processes downstream of tissue senescence. Climate can alter plant metabolism during the formative stage of tissues and could shape the final chemical composition of plant litter that is available for decomposition, and thus indirectly influence decomposition; however, these indirect effects are relatively poorly understood. Climatic stress disrupts cellular homeostasis in plants and results in the reprogramming of primary and secondary metabolic pathways, which leads to changes in the quantity, composition, and organization of small molecules and recalcitrant heteropolymers, including lignins, tannins, suberins, and cuticle within the plant tissue matrix. Furthermore, by regulating metabolism during tissue senescence, climate influences the resorption of nutrients from senescing tissues. Thus, the final chemical composition of plant litter that forms the substrate of decomposition is a combined product of presenescence physiological processes through the production and resorption of metabolites. The changes in quantity, composition, and localization of the molecular construct of the litter could enhance or hinder tissue decomposition and soil nutrient cycling by altering the recalcitrance of the lignocellulose matrix, the composition of microbial communities, and the activity of microbial exo-enzymes via various complexation reactions. Also, the climate-induced changes in the molecular composition of litter could differentially influence litter decomposition and soil nutrient cycling. Compared with temperate ecosystems, the indirect effects of climate on litter decomposition in the tropics are not well understood, which underscores the need to conduct additional studies in tropical biomes. We also emphasize the need to focus on how climatic stress affects the root chemistry as roots contribute significantly to biogeochemical cycling, and on utilizing more robust analytical approaches to capture the molecular composition of tissue matrix that fuel microbial metabolism. PMID- 28986958 TI - Characterizing selection in black-throated blue warblers using a sexual network approach. AB - Our understanding of trait evolution is built upon studies that examine the correlation between traits and fitness, most of which implicitly assume all individuals experience similar selective environments. However, accounting for differences in selective pressures, such as variation in the social environment, can advance our understanding of how selection shapes individual traits and subsequent fitness. In this study, we test whether variation in the social environment affects selection on individual phenotype. We apply a new sexual network framework to quantify each male's social environment as the mean body size of his primary competitors. We test for direct and social selection on male body size using a 10-year data set on black-throated blue warblers (Setophaga caerulescens), a territorial species for which body size is hypothesized to mediate competition for mates. We found that direct selection on body size was weak and nonsignificant, as was social selection via the body size of the males' competitors. Analysing both types of selection simultaneously allows us to firmly reject a role for body size in competitive interactions between males and subsequent male fitness in this population. We evaluate the application of the sexual network approach to empirical data and suggest that other phenotypic traits such as song characteristics and plumage may be more relevant than body size for male-male competition in this small passerine bird. PMID- 28986957 TI - The bulky and the sweet: How neutralizing antibodies and glycan receptors compete for virus binding. AB - Numerous viruses rely on glycan receptor binding as the initial step in host cell infection. Engagement of specific glycan receptors such as sialylated carbohydrates, glycosaminoglycans, or histo-blood group antigens can determine host range, tissue tropism, and pathogenicity. Glycan receptor-binding sites are typically located in exposed regions on viral surfaces-sites that are also generally prone to binding of neutralizing antibodies that directly interfere with virus-glycan receptor interactions. In this review, we examine the locations and architecture of the glycan- and antibody-binding sites in four different viruses with stalk-like attachment proteins (reovirus, influenza virus, norovirus, and coronavirus) and investigate the mechanisms by which antibodies block glycan recognition. Those viruses exemplify that direct molecular mimicking of glycan receptors by antibodies is rare and further demonstrate that antibodies often partly overlap or bind sufficiently close to the receptor-binding region to hinder access to this site, achieving neutralization partially because of the epitope location and partly due to their sheer size. PMID- 28986959 TI - Experimental and Computational Exploration of para-Selective Silylation with a Hydrogen-Bonded Template. AB - The regioselective conversion of C-H bonds into C-Si bonds is extremely important owing to the natural abundance and non-toxicity of silicon. Classical silylation reactions often suffer from poor functional group compatibility, low atom economy, and insufficient regioselectivity. Herein, we disclose a template assisted method for the regioselective para silylation of toluene derivatives. A new template was designed, and the origin of selectivity was analyzed experimentally and computationally. An interesting substrate-solvent hydrogen bonding interaction was observed. Kinetic, spectroscopic, and computational studies shed light on the reaction mechanism. The synthetic significance of this strategy was highlighted by the generation of a precursor of a potential lipophilic bioisostere of gamma-aminobutyric acid (GABA), various late-stage diversifications, and by mimicking enzymatic transformations. PMID- 28986961 TI - Know Your Variability: Challenges in Mechanistic Modeling of Inflammatory Response in Inflammatory Bowel Disease (IBD). PMID- 28986962 TI - Development of techniques for determination of primary components of dental medicament paste mixtures for root canal treatment. AB - AIMS: The purpose of the present study was to develop techniques to evaluate and quantify the primary components of dental medicament paste mixtures for root canal treatment, and to evaluate if degradation of the primary components occurred during storage. METHODS: The first part of the study developed a mass spectrometry (MS) method for determination of best recovery process. For this process, analytical grades of triamcinolone acetonide, clindamycin HCl, and doxycycline hyclate were sourced and analyzed. This was followed by solid-phase extraction (SPE) and an analysis of active components in dental pastes. RESULTS: By utilizing the targeted analytical properties of multiple reaction monitoring MS methods, coupled with SPE technique, the active components of endodontic dental pastes could be quantified and compared. The developed methods showed consistency over multiple runs, with a high level of reproducibility. None of the active components of the tested pastes degraded over the periods of product life tested. CONCLUSION: The inactivation or destruction of any of the primary components of endodontic medicaments in storage, or when mixed with other pastes, could affect treatment outcomes. The present study provides a reliable technique for the analysis of the active components of root canal medicaments. PMID- 28986963 TI - Development and evaluation of 'Pure Rush': An online serious game for drug education. AB - INTRODUCTION AND AIMS: Learning is most effective when it is active, enjoyable and incorporates feedback. Past research demonstrates that serious games are prime candidates to utilise these principles, however the potential benefits of this approach for delivering drug education are yet to be examined in Australia, a country where drug education in schools is mandatory. DESIGN AND METHODS: The serious game 'Pure Rush' was developed across three stages. First, formative consultation was conducted with 115 students (67% male, aged 15-17 years), followed by feasibility and acceptability testing of a prototype of the game (n = 25, 68% male). In the final stage, 281 students (62% female, aged 13-16 years) were randomly allocated to receive a lesson involving Pure Rush or an active control lesson. The lessons were compared in terms of learning outcomes, lesson engagement and future intentions to use illicit drugs. RESULTS: Students enjoyed playing Pure Rush, found the game age-appropriate and the information useful to them. Both the Pure Rush and the active control were associated with significant knowledge increase from pre to post-test. Among females, multi-level mixed effects regression showed knowledge gain was greater in the Pure Rush condition compared to control (beta = 2.36, 95% confidence interval 0.36-4.38). There was no evidence of between condition differences in lesson engagement or future intentions to use illicit drugs. DISCUSSION AND CONCLUSIONS: Pure Rush is an innovative online drug education game that is well received by students and feasible to implement in schools. [Stapinski LA, Reda B, Newton NC, Lawler S, Rodriguez D, Chapman C, Teesson M. Development and evaluation of 'Pure Rush': An online serious game for drug education. Drug Alcohol Rev 2017]. PMID- 28986960 TI - Bad wrap: Myelin and myelin plasticity in health and disease. AB - Human central nervous system myelin development extends well into the fourth decade of life, and this protracted period underscores the potential for experience to modulate myelination. The concept of myelin plasticity implies adaptability in myelin structure and function in response to experiences during development and beyond. Mounting evidence supports this concept of neuronal activity-regulated changes in myelin-forming cells, including oligodendrocyte precursor cell proliferation, oligodendrogenesis and modulation of myelin microstructure. In healthy individuals, myelin plasticity in associative white matter structures of the brain is implicated in learning and motor function in both rodents and humans. Activity-dependent changes in myelin-forming cells may influence the function of neural networks that depend on the convergence of numerous neural signals on both a temporal and spatial scale. However, dysregulation of myelin plasticity can disadvantageously alter myelin microstructure and result in aberrant circuit function or contribute to pathological cell proliferation. Emerging roles for myelin plasticity in normal neurological function and in disease are discussed. (c) 2017 Wiley Periodicals, Inc. Develop Neurobiol 78: 123-135, 2018. PMID- 28986964 TI - Escaping BRAF inhibition: A "linc" with non-coding RNAs? PMID- 28986966 TI - Vertical-cavity surface-emitting laser sources for gigahertz-bandwidth, multiwavelength frequency-domain photon migration. AB - Frequency-domain photon migration (FDPM) uses modulated laser light to measure the bulk optical properties of turbid media and is increasingly applied for noninvasive functional medical imaging in the near-infrared. Although semiconductor edge-emitting laser diodes have been traditionally used as miniature light sources for this application, we show that vertical-cavity surface-emitting lasers (VCSELs) exhibit output power and modulation performance characteristics suitable for FDPM measurements of tissue optical properties at modulation frequencies exceeding 1 GHz. We also show that an array of multiple VCSEL devices can be coherently modulated at frequencies suitable for FDPM and can improve optical power. In addition, their small size and simple packaging make them an attractive choice as components in wearable sensors and clinical FDPM-based optical spectroscopy systems. We demonstrate the benefits of VCSEL technology by fabricating and testing a unique, compact VCSEL-based optical probe with an integrated avalanche photodiode. We demonstrate sensitivity of the VCSEL based probe to subcutaneous tissue hemodynamics that was induced during an arterial cuff occlusion of the upper arm in a human subject. PMID- 28986968 TI - Uncovering the diagnostic dermoscopic features of flat melanomas located on the lower limbs. PMID- 28986967 TI - Enhanced tagging of light utilizing acoustic radiation force with speckle pattern analysis. AB - In optical imaging, the depth and resolution are limited due to scattering. Unlike light, scattering of ultrasound (US) waves in tissue is negligible. Hybrid imaging methods such as US-modulated optical tomography (UOT) use the advantages of both modalities. UOT tags light by inducing phase change caused by modulating the local index of refraction of the medium. The challenge in UOT is detecting the small signal. The displacement induced by the acoustic radiation force (ARF) is another US effect that can be utilized to tag the light. It induces greater phase change, resulting in a stronger signal. Moreover, the absorbed acoustic energy generates heat, resulting in change in the index of refraction and a strong phase change. The speckle pattern is governed by the phase of the interfering scattered waves; hence, speckle pattern analysis can obtain information about displacement and temperature changes. We have presented a model to simulate the insonation processes. Simulation results based on fixed-particle Monte Carlo and experimental results show that the signal acquired by utilizing ARF is stronger compared to UOT. The introduced mean irradiance change (MIC) signal reveals both thermal and mechanical effects of the focused US beam in different timescales. Simulation results suggest that variation in the MIC signal can be used to generate a displacement image of the medium. PMID- 28986965 TI - Neurodevelopmental disease mechanisms, primary cilia, and endosomes converge on the BLOC-1 and BORC complexes. AB - The biogenesis of lysosome-related organelles complex-1 (BLOC-1) and the bloc-one related complex (BORC) are the cytosolic protein complexes required for specialized membrane protein traffic along the endocytic route and the spatial distribution of endosome-derived compartments, respectively. BLOC-1 and BORC complex subunits and components of their interactomes have been associated with the risk and/or pathomechanisms of neurodevelopmental disorders. Thus, cellular processes requiring BLOC-1 and BORC interactomes have the potential to offer novel insight into mechanisms underlying behavioral defects. We focus on interactions between BLOC-1 or BORC subunits with the actin and microtubule cytoskeleton, membrane tethers, and SNAREs. These interactions highlight requirements for BLOC-1 and BORC in membrane movement by motors, control of actin polymerization, and targeting of membrane proteins to specialized cellular domains such as the nerve terminal and the primary cilium. We propose that the endosome-primary cilia pathway is an underappreciated hub in the genesis and mechanisms of neurodevelopmental disorders. (c) 2017 Wiley Periodicals, Inc. Develop Neurobiol 78: 311-330, 2018. PMID- 28986969 TI - Escherichia coli DNA polymerase I can disrupt G-quadruplex structures during DNA replication. AB - Non-canonical four-stranded G-quadruplex (G4) DNA structures can form in G-rich sequences that are widely distributed throughout the genome. The presence of G4 structures can impair DNA replication by hindering the progress of replicative polymerases (Pols), and failure to resolve these structures can lead to genetic instability. In the present study, we combined different approaches to address the question of whether and how Escherichia coli Pol I resolves G4 obstacles during DNA replication and/or repair. We found that E. coli Pol I-catalyzed DNA synthesis could be arrested by G4 structures at low protein concentrations and the degree of inhibition was strongly dependent on the stability of the G4 structures. Interestingly, at high protein concentrations, E. coli Pol I was able to overcome some kinds of G4 obstacles without the involvement of other molecules and could achieve complete replication of G4 DNA. Mechanistic studies suggested that multiple Pol I proteins might be implicated in G4 unfolding, and the disruption of G4 structures requires energy derived from dNTP hydrolysis. The present work not only reveals an unrealized function of E. coli Pol I, but also presents a possible mechanism by which G4 structures can be resolved during DNA replication and/or repair in E. coli. PMID- 28986970 TI - Li2 MnSnSe4 : A New Quaternary Diamond-Like Semiconductor with Nonlinear Optical Response and Antiferromagnetic Property. AB - A new selenide with a diamond-like structure, Li2 MnSnSe4 , was synthesized for the first time by using a conventional high-temperature solid-state reaction method. Li2 MnSnSe4 crystallizes in the space group Pmn21 (no. 31) of the orthorhombic system. Its three-dimensional framework is constructed by corner sharing LiSe4 , MnSe4 , and SnSe4 tetrahedra. The title compound has been discovered to have both type I phase-matchable behavior and to exhibit moderate powder second-harmonic generation intensity, about 0.5 times that of commercial AgGaS2 in the particle size of 200-250 MUm at a laser radiation of 2.09 MUm. In addition, Li2 MnSnSe4 exhibits congruent melting behavior, which makes the bulk single-crystal growth by the Bridgman-Stockbarger method possible. The temperature-dependent susceptibility measurement indicates an antiferromagnetic interaction with a Neel temperature (TN ) of 8.6 K for this compound. PMID- 28986972 TI - Invasive breast carcinomas with ATM gene variants of uncertain significance share distinct histopathologic features. AB - The increasing availability of next-generation sequencing for clinical research dramatically improved our understanding of breast cancer genetics and resulted in detection of new mutation variants. Cancer risk data relating to some of these variants are insufficient, prompting the designation of variants of uncertain significance (VUS). The histopathologic characteristics of these variants have not been previously described. We propose to depict these characteristics and determine if invasive carcinomas with similar VUS genes share similar histomorphologic features. In total, 28 invasive breast cancers with VUS were retrospectively identified. Tumor sections were reviewed and a predefined set of histopathologic characteristics were documented and compared. Nine of the 28 cases were variants in the ATM gene and were found to share similar histologic characteristics; all had tumor cells with low nuclear grade, absent tumor infiltrating lymphocytes, as well as a marked desmoplastic response. A subset of the above findings were identified in variants of other genes but none had all findings collectively. Furthermore, variants of ATM gene had smaller tumor size, lower pathologic T stage at presentation, and more favorable surrogate molecular subtype compared to variants of other genes. These findings could potentially be used to reclassify VUS and predict which patients may harbor ATM mutations, and hence could have implications in triaging toward ATM variant identification for potential future targeted therapy. PMID- 28986974 TI - A review of methods for the chemical characterization of cannabis natural products. AB - Cannabis has garnered a great deal of new attention in the past couple of years in the United States due to the increasing instances of its legalization for recreational use and indications for medicinal benefit. Despite a growing number of laboratories focused on cannabis analysis, the separation science literature pertaining to the determination of cannabis natural products is still in its infancy despite the plant having been utilized by humans for nearly 30 000 years and it being now the most widely used drug worldwide. This is largely attributable to the restrictions associated with cannabis as it is characterized as a schedule 1 drug in the United States. Presented here are reviewed analytical methods for the determination of cannabinoids (primarily) and terpenes (secondarily), the primary natural products of interest in cannabis plants. Focus is placed foremost on analyses from plant extracts and the various instrumentation and techniques that are used, but some coverage is also given to analysis of cannabinoid metabolites found in biological fluids. The goal of this work is to provide a collection of relevant separation science information, upon which the field of cannabis analysis can continue to grow. PMID- 28986971 TI - Redefining "Learning" in Statistical Learning: What Does an Online Measure Reveal About the Assimilation of Visual Regularities? AB - From a theoretical perspective, most discussions of statistical learning (SL) have focused on the possible "statistical" properties that are the object of learning. Much less attention has been given to defining what "learning" is in the context of "statistical learning." One major difficulty is that SL research has been monitoring participants' performance in laboratory settings with a strikingly narrow set of tasks, where learning is typically assessed offline, through a set of two-alternative-forced-choice questions, which follow a brief visual or auditory familiarization stream. Is that all there is to characterizing SL abilities? Here we adopt a novel perspective for investigating the processing of regularities in the visual modality. By tracking online performance in a self paced SL paradigm, we focus on the trajectory of learning. In a set of three experiments we show that this paradigm provides a reliable and valid signature of SL performance, and it offers important insights for understanding how statistical regularities are perceived and assimilated in the visual modality. This demonstrates the promise of integrating different operational measures to our theory of SL. PMID- 28986975 TI - Complete kinetic follow-up of symptoms and complement parameters during a hereditary angioedema attack. AB - We studied the kinetics of C1-inhibitor (C1-INH) and other complement parameters in a self-limited edematous attack (EA) in a patient with hereditary angioedema due to C1-INH deficiency to better understand the pathomechanism of the evolution, course, and complete resolution of EAs. C1-INH concentration and functional activity (C1-INHc+f ), C1(q,r,s), C3, C4, C3a, C4a, C5a, and SC5b-9 levels were measured in blood samples obtained during the 96-hour observation period. The highest C1-INHc+f , C4, and C1(q,r,s) levels were measured at baseline, and their continuous decrease was observed during the entire observation period. C4 depletion started at prodromal phase, and C4 was lowest after the maximum severity peak. Compared to baseline, C4a level was four times higher 7 hours before the onset of the attack. C1-INH did not increase after resolution of the attack suggesting that factors other than C1-INH may be important in this process. C4a may be a useful biomarker for the prediction of EAs. PMID- 28986976 TI - Development of an international core outcome set for peripheral vascular malformations: the OVAMA project. AB - BACKGROUND: An important limitation in vascular malformation research is the heterogeneity in outcome measures used for the evaluation of treatment outcome. OBJECTIVES: To reach international consensus on a core outcome set (COS) for clinical research on peripheral vascular malformations: lymphatic (LM), venous (VM) and arteriovenous malformations (AVM). In this consensus study, we determined what domains should constitute the COS. METHODS: Thirty-six possibly relevant outcome domains were proposed to an international group of physicians, patients and the parents of patients. In a three-round e-Delphi process using online surveys, participants repeatedly rated the importance of these domains on a five-point Likert scale. Participants could also propose other relevant domains. This process was performed for LM, VM and AVM separately. Consensus was predefined as 80% agreement on the importance of a domain among both the physician group and the patient/parent group. Outcomes were then re-evaluated in an online consensus meeting. RESULTS: 167 physicians and 134 patients and parents of patients with LM (n = 50), VM (n = 71) and AVM (n = 29) participated in the study. After three rounds and a consensus meeting, consensus was reached for all three types of vascular malformations on the core domains of radiological assessment, physician-reported location-specific signs, patient-reported severity of symptoms, pain, quality of life, satisfaction and adverse events. Vascular malformation type-specific signs and symptoms were included for LM, VM and AVM, separately. CONCLUSIONS: Our recommendation is that therapeutic-efficacy studies on peripheral vascular malformations should measure at least these core outcome domains. PMID- 28986977 TI - The class pictures in citizens' minds. AB - Social class has traditionally played a key role in explaining social behaviour and cognition. However, recent analyses have been dominated by the view that the relevance of class for behaviour has dwindled in advanced industrial societies. We contest this view by focusing on the subjective components of class consciousness. Using a national survey of Danish citizens, we show that individuals continue to hold meaningful conceptions of classes, to identify with them and, moreover, to perceive substantial levels of differences between them with these latter beliefs being strongly structured by respondent class identification. These results are all the more intriguing because they stem from a high affluence/low inequality national context that should be a particularly good case for failing to find such rich class perceptions. PMID- 28986978 TI - Comparison of platform host cell protein ELISA to process-specific host cell protein ELISA. AB - During expression of biotherapeutic proteins, complex mixtures of additional proteins are also produced by normal expression machinery of the host cell (termed "host cell proteins," or HCP). HCPs pose a potential impact to patient safety and product efficacy, and therefore must be well-characterized and the ability of the process to clear these proteins must be demonstrated. Due to the complexity of HCP, the method(s) used for monitoring must be demonstrated to provide sufficient information about relevant proteins. The most commonly used analytical method for monitoring HCP is an enzyme-linked immunosorbent assay (ELISA). To ensure development of a suitable HCP ELISA, careful selection of critical reagents (anti-HCP antibodies and analytical standard) is crucial. During a recent major update to the manufacturing process of a biotherapeutic, we re-evaluated the suitability of the existing HCP ELISA for monitoring the HCP population in the updated process. In the evaluation, we compared a process specific ELISA to a platform ELISA. Despite qualitative differences in the HCP profiles in 2D PAGE, LC-MS/MS showed that the HCP populations in the two analytical standards were similar. The process-specific HCP antibody had adequate HCP coverage, but was more sensitive to a few dominant proteins that were present in the upstream purification process. The platform HCP antibody had very broad coverage and additionally, could detect the majority of potential HCP impurities from this process. Furthermore, the platform HCP antibody was not biased toward a few dominant proteins and was more sensitive in the downstream purification process. Due to its broad HCP coverage and sensitivity, we conclude that our platform HCP ELISA method is superior to the process-specific HCP ELISA method. PMID- 28986979 TI - Inorganic pyrophosphatases of Family II-two decades after their discovery. AB - Inorganic pyrophosphatases (PPases) convert pyrophosphate (PPi ) to phosphate and are present in all cell types. Soluble PPases belong to three nonhomologous families, of which Family II is found in approximately a quarter of prokaryotic organisms, often pathogenic ones. Each subunit of dimeric canonical Family II PPases is formed by two domains connected by a flexible linker, with the active site located between the domains. These enzymes require both magnesium and a transition metal ion (manganese or cobalt) for maximal activity and are the most active (kcat ~ 104 s-1 ) among all PPase types. Catalysis by Family II PPases requires four metal ions per substrate molecule, three of which form a unique trimetal center that coordinates the nucleophilic water and converts it to a reactive hydroxide ion. A quarter of Family II PPases contain an autoinhibitory regulatory insert formed by two cystathionine beta-synthase (CBS) domains and one DRTGG domain. Adenine nucleotide binding either activates or inhibits the CBS domain-containing PPases, thereby tuning their activity and, hence, PPi levels, in response to changes in cell energy status (ATP/ADP ratio). PMID- 28986980 TI - Metabolic engineering of Bacillus subtilis for production of D-lactic acid. AB - Poly lactic acid (PLA) based plastics is renewable, bio-based, and biodegradable. Although present day PLA is composed of mainly L-LA, an L- and D- LA copolymer is expected to improve the quality of PLA and expand its use. To increase the number of thermotolerant microbial biocatalysts that produce D-LA, a derivative of Bacillus subtilis strain 168 that grows at 50 degrees C was metabolically engineered. Since B. subtilis lacks a gene encoding D-lactate dehydrogenase (ldhA), five heterologous ldhA genes (B. coagulans ldhA and gldA101, and ldhA from three Lactobacillus delbrueckii) were evaluated. Corresponding D-LDHs were purified and biochemically characterized. Among these, D-LDH from L. delbrueckii subspecies bulgaricus supported the highest D-LA titer (about 1M) and productivity (2 g h-1 g cells-1 ) at 37 degrees C (B. subtilis strain DA12). The D-LA titer at 48 degrees C was about 0.6 M at a yield of 0.99 (g D-LA g-1 glucose consumed). Strain DA12 also fermented glucose at 48 degrees C in mineral salts medium to lactate at a yield of 0.89 g g-1 glucose and the D-lactate titer was 180 +/- 4.5 mM. These results demonstrate the potential of B. subtilis as a platform organism for metabolic engineering for production of chemicals at 48 degrees C that could minimize process cost. PMID- 28986981 TI - The new subversive geranium: some notes on the management of additional troubles in maximum security prisons. AB - In this paper, we revisit King and McDermott's 1990 article on the social construction of 'control problem' prisoners and their management in high security prisons, in the light of our recent research on the location and building of trust in contemporary high security prisons. We examine how religious and race identities are now deeply implicated in the construction of risk, and we describe the procedures for and some of the consequences of managing the new risks of radicalization and extremist violence in prison. The analysis is based on observations and interviews with staff and prisoners in two main and two supplementary maximum-security prisons in England and Wales. PMID- 28986982 TI - EEG for children with complex febrile seizures. AB - BACKGROUND: Febrile seizures can be classified as simple or complex. Complex febrile seizures are associated with fever that lasts longer than 15 minutes, occur more than once within 24 hours, and are confined to one side of the child's body. It is common in some countries for doctors to recommend an electroencephalograph (EEG) for children with complex febrile seizures. A limited evidence base is available to support the use of EEG and its timing after complex febrile seizures among children. OBJECTIVES: To assess the use of EEG and its timing after complex febrile seizures in children younger than five years of age. SEARCH METHODS: For the latest update of this review, we searched the Cochrane Epilepsy Group Specialized Register (23 January 2017), the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (CRSO, 23 January 2017), MEDLINE (Ovid, 23 January 2017), and ClinicalTrials.gov (23 January 2017). We applied no language restrictions. SELECTION CRITERIA: All randomised controlled trials (RCTs) that examined the utility of an EEG and its timing after complex febrile seizures in children. DATA COLLECTION AND ANALYSIS: The review authors selected and retrieved the articles and independently assessed which articles should be included. Any disagreements were resolved by discussion and by consultation with the Cochrane Epilepsy Group. We applied standard methodological procedures expected by Cochrane. MAIN RESULTS: Of 41 potentially eligible studies, no RCTs met the inclusion criteria. AUTHORS' CONCLUSIONS: We found no RCTs as evidence to support or refute the use of EEG and its timing after complex febrile seizures among children. An RCT can be planned in such a way that participants are randomly assigned to the EEG group and to the non-EEG group with sufficient sample size. Since the last version of this review, we have found no new studies. PMID- 28986983 TI - Enzymatic synthesis of chiral amino-alcohols by coupling transketolase and transaminase-catalyzed reactions in a cascading continuous-flow microreactor system. AB - Rapid biocatalytic process development and intensification continues to be challenging with currently available methods. Chiral amino-alcohols are of particular interest as they represent key industrial synthons for the production of complex molecules and optically pure pharmaceuticals. (2S,3R)-2-amino-1,3,4 butanetriol (ABT), a building block for the synthesis of protease inhibitors and detoxifying agents, can be synthesized from simple, non-chiral starting materials, by coupling a transketolase- and a transaminase-catalyzed reaction. However, until today, full conversion has not been shown and, typically, long reaction times are reported, making process modifications and improvement challenging. In this contribution, we present a novel microreactor-based approach based on free enzymes, and we report for the first time full conversion of ABT in a coupled enzyme cascade for both batch and continuous-flow systems. Using the compartmentalization of the reactions afforded by the microreactor cascade, we overcame inhibitory effects, increased the activity per unit volume, and optimized individual reaction conditions. The transketolase-catalyzed reaction was completed in under 10 min with a volumetric activity of 3.25 U ml-1 . Following optimization of the transaminase-catalyzed reaction, a volumetric activity of 10.8 U ml-1 was attained which led to full conversion of the coupled reaction in 2 hr. The presented approach illustrates how continuous-flow microreactors can be applied for the design and optimization of biocatalytic processes. PMID- 28986984 TI - Component-resolved diagnosis and beyond: Multivariable regression models to predict severity of hazelnut allergy. AB - BACKGROUND: Component-resolved diagnosis (CRD) has revealed significant associations between IgE against individual allergens and severity of hazelnut allergy. Less attention has been given to combining them with clinical factors in predicting severity. AIM: To analyze associations between severity and sensitization patterns, patient characteristics and clinical history, and to develop models to improve predictive accuracy. METHODS: Patients reporting hazelnut allergy (n = 423) from 12 European cities were tested for IgE against individual hazelnut allergens. Symptoms (reported and during Double-blind placebo controlled food challenge [DBPCFC]) were categorized in mild, moderate, and severe. Multiple regression models to predict severity were generated from clinical factors and sensitization patterns (CRD- and extract-based). Odds ratios (ORs) and areas under receiver-operating characteristic (ROC) curves (AUCs) were used to evaluate their predictive value. RESULTS: Cor a 9 and 14 were positively (OR 10.5 and 10.1, respectively), and Cor a 1 negatively (OR 0.14) associated with severe symptoms during DBPCFC, with AUCs of 0.70-073. Combining Cor a 1 and 9 improved this to 0.76. A model using a combination of atopic dermatitis (risk), pollen allergy (protection), IgE against Cor a 14 (risk) and walnut (risk) increased the AUC to 0.91. At 92% sensitivity, the specificity was 76.3%, and the positive and negative predictive values 62.2% and 95.7%, respectively. For reported symptoms, associations and generated models proved to be almost identical but weaker. CONCLUSION: A model combining CRD with clinical background and extract-based serology is superior to CRD alone in assessing the risk of severe reactions to hazelnut, particular in ruling out severe reactions. PMID- 28986985 TI - An evolutionary tipping point in a changing environment. AB - Populations can persist in directionally changing environments by evolving. Quantitative genetic theory aims to predict critical rates of environmental change beyond which populations go extinct. Here, we point out that all current predictions effectively assume the same specific fitness function. This function causes selection on the standing genetic variance of quantitative traits to become increasingly strong as mean trait values depart from their optima. Hence, there is no bound on the rate of evolution and persistence is determined by the critical rate of environmental change at which populations cease to grow. We then show that biologically reasonable changes to the underlying fitness function can impose a qualitatively different extinction threshold. In particular, inflection points caused by weakening selection create local extrema in the strength of selection and thus in the rate of evolution. These extrema can produce evolutionary tipping points, where long-run population growth rates drop from positive to negative values without ever crossing zero. Generic early-warning signs of tipping points are found to have little power to detect imminent extinction, and require hard-to-gather data. Furthermore, we show how evolutionary tipping points produce evolutionary hysteresis, creating extinction debts. PMID- 28986986 TI - Depletion of Mast Cells and Macrophages Impairs Heterotopic Ossification in an Acvr1R206H Mouse Model of Fibrodysplasia Ossificans Progressiva. AB - Heterotopic ossification (HO) is a clinical condition that often reduces mobility and diminishes quality of life for affected individuals. The most severe form of progressive HO occurs in those with fibrodysplasia ossificans progressiva (FOP; OMIM #135100), a genetic disorder caused by a recurrent heterozygous gain-of function mutation (R206H) in the bone morphogenetic protein (BMP) type I receptor ACVR1/ALK2. In individuals with FOP, episodes of HO frequently follow injury. The first sign of active disease is commonly an inflammatory "flare-up" that precedes connective tissue degradation, progenitor cell recruitment, and endochondral HO. We used a conditional-on global knock-in mouse model expressing Acvr1R206H (referred to as Acvr1cR206H/+ ) to investigate the cellular and molecular inflammatory response in FOP lesions following injury. We found that the Acvr1 R206H mutation caused increased BMP signaling in posttraumatic FOP lesions and early divergence from the normal skeletal muscle repair program with elevated and prolonged immune cell infiltration. The proinflammatory cytokine response of TNFalpha, IL-1beta, and IL-6 was elevated and prolonged in Acvr1cR206H/+ lesions and in Acvr1cR206H/+ mast cells. Importantly, depletion of mast cells and macrophages significantly impaired injury-induced HO in Acvr1cR206H/+ mice, reducing injury-induced HO volume by ~50% with depletion of each cell population independently, and ~75% with combined depletion of both cell populations. Together, our data show that the immune system contributes to the initiation and development of HO in FOP. Further, the expression of Acvr1R206H in immune cells alters cytokine expression and cellular response to injury and unveils novel therapeutic targets for treatment of FOP and nongenetic forms of HO. (c) 2017 American Society for Bone and Mineral Research. PMID- 28986987 TI - Monte Carlo simulations of a kilovoltage external beam radiotherapy system on phantoms and breast patients. AB - PURPOSE: To determine the most suitable lesion size and depth for radiotherapy treatments with a prototype kilovoltage x-ray arc therapy (KVAT) system through Monte Carlo simulations of the dose delivered to lesion, dose homogeneity, and lesion-to-skin ratio. METHODS: Monte Carlo simulations were used to calculate dose distributions generated by a novel low-energy kilovoltage x-ray system to a variety of clinically relevant lesion sizes and depths in phantoms and for hypothetical partial breast irradiations of patients in supine and prone positions. The treatments by 200 kV KVAT system were modeled for four sizes of tumor (1-4 cm diameter) at three depths (superficial, middle, and deep) in two sizes of cylindrical water phantoms (16.2-cm and 32.2-cm diameter). In addition, treatments of 3-cm and 4-cm diameter lesions were modeled for two breast patients in prone and supine positions. Dose distributions were calculated using the EGSnrc/DOSXYZnrc code package. Phantom study metrics included lesion-to-skin ratio, dose delivered to isocenter (cGy/min), dose homogeneity, dose profiles, and cumulative dose volume histograms. Lesion-to-skin ratio, lesion-to-rib ratio, dose profiles, and cumulative dose volume histograms were used to evaluate simulated breast patient treatments. Supine breast irradiations were compared to 6-MV VMAT plans. The criterion applied to evaluate the dose distributions was derived from NSABP-B39/RTOG 0413 for accelerated partial breast irradiation. Skin dose was limited to a maximum of 250 cGy for a prescribed lesion dose of 385 cGy per fraction (with the whole treatment being delivered in 10 fractions). This produced the minimum lesion-to-skin dose ratio of 1.5 that served as the main guideline, along with other metrics, for evaluation of future clinical viability of treatments. RESULTS: Phantom dose distributions in the centrally located lesions treated with 360-degree KVAT were found to be superior to dose distributions in off-center lesions with the exception of isocenter dose, which was highest for lesions located closer to the phantom surface. Dose metrics were more favorable for smaller lesions, suggesting that KVAT might be most suitable for treatment of lesions of 1-2 cm in diameter down to depths of 8.1 cm along with 3 cm lesions at depths from 3 cm to 8.1 cm. In addition, treatments of 4-cm lesions were found to be acceptable down to the depths of 4.1 cm (in the 16.2-cm phantom) and 8.1 cm (in the 32.2-cm phantom). At depths from 8.1-cm to 16.1-cm, treatments of 1-cm to 4-cm lesions are possible at the cost of decreased dose rate. KVAT breast treatments in the supine patient position demonstrated that increasing the arc angle and decreasing lesion size improved lesion-to-skin ratio and lesion-to-rib ratio. Supine breast data indicate that 3-cm lesions are treatable at a minimum depth of 3 cm. The 6-MV VMAT plan resulted in lower doses to the ipsilateral lung and the body, but a higher heart dose compared to the KVAT plans. Dose distributions for the prone breast phantoms were superior to the supine cases due to the increased treatment angle of 360-degrees. CONCLUSIONS: Although nonoptimized KVAT dose distributions presented here were of inferior quality to VMAT plans, this work has demonstrated the feasibility of delivering low-energy kilovoltage x-rays to lesions up to 4 cm in diameter to depths of 8.1 cm while sparing surrounding tissue. PMID- 28986988 TI - Alveolar herniation in transbronchial lung biopsy: a newly recognised diagnostic pitfall. PMID- 28986989 TI - Utility of Phox2b immunohistochemical stain in neural crest tumours and non neural crest tumours in paediatric patients. AB - AIMS: This study evaluated the utility of Phox2b in paediatric tumours. Previously, tyrosine hydroxylase (TH) was the most widely utilised sympathoadrenal marker specific for neural crest tumours with neuronal/neuroendocrine differentiation. However, its sensitivity is insufficient. Recently Phox2b has emerged as another specific marker for this entity. METHODS AND RESULTS: Phox2b immunohistochemistry (IHC) was performed on 159 paediatric tumours, including (group 1) 65 neural crest tumours with neuronal differentiation [peripheral neuroblastic tumours (pNT)]: 15 neuroblastoma undifferentiated (NB-UD), 10 NB poorly differentiated (NB-PD), 10 NB differentiating (NB-D), 10 ganglioneuroblastoma intermixed (GNBi), 10 GNB nodular (GNBn) and 10 ganglioneuroma (GN); (group 2) 23 neural crest tumours with neuroendocrine differentiation [pheochromocytoma/paraganglioma (PCC/PG)]; (group 3) 27 other neural crest tumours including one composite rhabdomyosarcoma/neuroblastoma; and (group 4) 44 non-neural crest tumours. TH IHC was performed on groups 1, 2 and 3. Phox2b was expressed diffusely in pNT (n = 65 of 65), strongly in NB-UD and NB-PD and with less intensity in NB-D, GNB and GN. Diffuse TH was seen in all NB-PD, NB-D, GNB and GN, but nine of 15 NB-UD and a nodule in GNBn did not express TH (n = 55 of 65). PCC/PG expressed diffuse Phox2b (n = 23 of 23) and diffuse TH, except for one tumour (n = 22 of 23). In composite rhabdomyosarcoma, TH was expressed only in neuroblastic cells and Phox2b was diffusely positive in neuroblastic cells and focally in rhabdomyosarcoma. All other tumours were negative for Phox2b (n = none of 44). CONCLUSION: Phox2b was a specific and sensitive marker for pNT and PCC/PG, especially useful for identifying NB-UD often lacking TH. Our study also presented a composite rhabdomyosarcoma/neuroblastoma of neural crest origin. PMID- 28986990 TI - High blood pressure in the young: why should we care? AB - : While primary hypertension (HTN) clearly occurs in children and adolescents, the approach of many providers to such patients can best be described as ambivalent: the condition may be recognised, but is not acted upon. Such ambivalence may stem from incomplete understanding of the effects of high blood pressure in the young, which in turn is related to the shortage of information on long-term outcomes of primary childhood HTN. However, other evidence on the short and long-term effects of blood pressure elevation in childhood clearly shows that it is not a benign condition at all. CONCLUSION: Childhood HTN warrants action to prevent adult cardiovascular disease. PMID- 28986991 TI - Occurrence and distribution of organophosphate ester flame retardants in indoor dust and their potential health exposure risk. AB - The occurrence and distribution of 10 organophosphate ester (OP) flame retardants/plasticizers were studied in indoor dust collected in 2 districts of Wuhan City. Total concentrations of the 10 OPs (SigmaOPs) varied from 86.5 to 6389 ng/g in 26 dust samples in Caidian District and from 300 to 10 186 ng/g in 27 samples in Jiang'an District. In most dust samples tris(2-chloroethyl) phosphate was dominant over the other OPs, with concentrations of 9.14 to 2722 ng/g (mean 388 ng/g) in Caidian District and 57.3 to 3718 ng/g (mean 616 ng/g) in Jiang'an District. The calculated hazard indices, based on estimated exposure dose via dust ingestion to the reference dose, were much lower than 1. The results suggested that the inhabitants in the 2 regions were at low risk of exposure through dust ingestion. Environ Toxicol Chem 2018;37:345-352. (c) 2017 SETAC. PMID- 28986992 TI - Mixtures of Cu, Ni, and Zn act mostly noninteractively on Pseudokirchneriella subcapitata growth in natural waters. AB - Freshwater biota are usually exposed to mixtures of different metals in the environment, which raises concern because risk-assessment procedures for metals are still mainly based on single-metal toxicity. Because microalgae are primary producers and therefore at the base of the food web, it is of utmost importance to understand the effects of metal mixtures on these organisms. Most studies that have investigated the combined interactive effects of mixtures on microalgae performed tests in only one specific water. The objective of the present study was to test if combined effects of mixtures to Pseudokirchneriella subcapitata were the same or different across natural waters showing diverse water-chemistry characteristics. This was done by performing experiments with ternary Cu-Ni-Zn mixtures in 3 natural waters and with binary Cu-Ni mixtures in 5 natural waters. We showed that the ternary mixture acted noninteractively on algal growth, except in one water in which the mixture acted antagonistically. We suggest that a low cationic competition situation in the latter water could be the reason for the antagonistic interaction between the metals. On the other hand, the binary mixture acted noninteractively on algal growth in all tested waters. We showed that both the concentration addition and independent action models can serve as accurate models for toxicity of ternary Cu-Ni-Zn and binary Cu-Ni mixtures to P. subcapitata in most cases and as protective models in all cases. In addition, we developed a metal mixture bioavailability model, by combining the independent action model and the single-metal bioavailability models, that can be used to predict Cu-Ni-Zn and Cu-Ni toxicity to P. subcapitata as a function of metal concentration and water characteristics. Environ Toxicol Chem 2018;37:587-598. (c) 2017 SETAC. PMID- 28986993 TI - Children in out-of-home care are at high risk of somatic, dental and mental ill health. AB - AIM: The Swedish Social Board has implemented a support strategy to guide out-of home care for children, which translates as children's needs in focus (CNIF) and includes a systematic health assessment. It was fully introduced into the Skane province in 2012 and our study covered the first four years of the CNIF health assessments, from 2012 to 2015. METHODS: We studied children aged 0-17 years in out-of-home care who had been referred by social workers for a CNIF health assessment, using their medical records to investigate both their health and the value of the health assessments. RESULT: From 2012 to 2015, only 409 (6%) of the 11 413 children in out-of-home care were referred for health assessments. Their health issues included depression and anxiety (29%), poor dental health (30%), seeking medical care for traumatic injuries (36%), previous contact with child psychiatry services (38%) and missed medical appointments (36%), dental appointments (36%) and child health programme appointments (39%). In addition, 10% of the girls and 9% of the boys were obese. CONCLUSION: This study found high levels of wide-ranging health issues. Despite national Swedish guidelines and policies, only 6% of the children in out-of-home care were referred by social workers for a CNIF health assessment. PMID- 28986994 TI - Microvasculature dropout detected by the optical coherence tomography angiography in nonarteritic anterior ischemic optic neuropathy. AB - OBJECTIVE: To investigate microcirculation characteristics of peripapillary superficial retina and optic disc in eyes with nonarteritic anterior ischemic optic neuropathy (NAION) using optical coherence tomography angiography (OCTA). METHODS: Forty-one eyes of 30 NAION patients and 30 eyes of 30 normal subjects were evaluated with OCTA (AngioVue, Optovue). The whole vessel density, inside disc vessel density, peripapillary vessel density, and vessel densities based on the sectorial division in the nerve head mode peripapillary superficial retina and RPC mode optic disc were measured respectively. RESULTS: In the NAION group, vessel densities in both the peripapillary superficial retina and optic disc were significant reduced (P < 0.01), as compared with the control group. The whole vessel density of the optic disc in chronic NAION group were significantly lower than that in acute NAION group (P < 0.01). The whole and temporal vessel density of the peripapillary superficial retina was significantly correlated with log MAR VA (r = -0.381 and r = -0.337, both P < 0.05). Vessel densities in both the peripapillary superficial retina and optic disc were reduced (P < 0.05) in unilateral involved eyes, as compared to the unaffected fellow eyes, except for the inside disc (P = 0.270) and SN (P = 0.054) vessel density in the optic disc, while there was no difference in the fellow eyes compared to the normal eyes. CONCLUSION: In NAION patients, a dropout of microvasculature in peripapillary superficial retina and optic disc could be detected by OCTA directly. OCTA might become a useful tool for detection and monitoring of NAION. Lasers Surg. Med. 50:194-201, 2018. (c) 2017 Wiley Periodicals, Inc. PMID- 28986995 TI - Biocatalytic conversion of cycloalkanes to lactones using an in-vivo cascade in Pseudomonas taiwanensis VLB120. AB - Chemical synthesis of lactones from cycloalkanes is a multi-step process challenged by limitations in reaction efficiency (conversion and yield), atom economy (by-products) and environmental performance. A heterologous pathway comprising novel enzymes with compatible kinetics was designed in Pseudomonas taiwanensis VLB120 enabling in-vivo cascade for synthesizing lactones from cycloalkanes. The respective pathway included cytochrome P450 monooxygenase (CHX), cyclohexanol dehydrogenase (CDH), and cyclohexanone monooxygenase (CHXON) from Acidovorax sp. CHX100. Resting (non-growing) cells of the recombinant host P. taiwanensis VLB120 converted cyclohexane, cyclohexanol, and cyclohexanone to epsilon-caprolactone at 22, 80-100, and 170 U gCDW-1 , respectively. Cyclohexane (5 mM) was completely converted with a selectivity of 65% for epsilon caprolactone formation in 2 hr without accumulation of intermediate products. Promiscuity of the whole-cell biocatalyst gave access to analogous lactones from cyclooctane and cyclodecane. A total product concentration of 2.3 g L-1 and a total turnover number of 36,720 was achieved over 5 hr with a biocatalyst concentration of 6.8 gCDW L-1 . PMID- 28986996 TI - Metabolite profiling of ginsenosides in rat plasma, urine and feces by LC-MS/MS and its application to a pharmacokinetic study after oral administration of Panax ginseng extract. AB - Panax ginseng is widely consumed as a functional food in the form of tea, powder, capsules, among others, and possesses a range of pharmacological activities including adaptogenic, immune-modulatory, anti-tumor, anti-aging and anti inflammatory effects. The aim of this study was to identify and quantify the major ginsenosides and their metabolites in rat plasma, urine and feces after administration of P. ginseng extract using LC-MS/MS. We collected rat plasma samples at 0.5, 1, 2, 4, 8, 12, 24 and 48 h, and the amounts of urine and fecal samples accumulated in 24 h. Fourteen major ginsenosides and their metabolites were observed in fecal samples at high levels; however, low levels of 11 ginsenosides were detected in urine samples. The pharmacokinetics of the major ginsenosides and their metabolites was investigated in plasma. The results indicated that the maximum plasma concentration, time to maximum concentration and area under the curve of compound K were significantly greater than those of other ginsenosides. This study thus provides valuable information for drug development and clinical application of P. ginseng. PMID- 28986998 TI - A synthetic biology approach to transform Yarrowia lipolytica into a competitive biotechnological producer of beta-carotene. AB - The increasing market demands of beta-carotene as colorant, antioxidant and vitamin precursor, requires novel biotechnological production platforms. Yarrowia lipolytica, is an industrial organism unable to naturally synthesize carotenoids but with the ability to produce high amounts of the precursor Acetyl-CoA. We first found that a lipid overproducer strain was capable of producing more beta carotene than a wild type after expressing the heterologous pathway. Thereafter, we developed a combinatorial synthetic biology approach base on Golden Gate DNA assembly to screen the optimum promoter-gene pairs for each transcriptional unit expressed. The best strain reached a production titer of 1.5 g/L and a maximum yield of 0.048 g/g of glucose in flask. beta-carotene production was further increased in controlled conditions using a fed-batch fermentation. A total production of beta-carotene of 6.5 g/L and 90 mg/g DCW with a concomitant production of 42.6 g/L of lipids was achieved. Such high titers suggest that engineered Y. lipolytica is a competitive producer organism of beta-carotene. PMID- 28986997 TI - PGE1 and E3 show lower efficacies than E2 to beta-catenin-mediated activity as biased ligands of EP4 prostanoid receptors. AB - The 2-series of prostaglandin E (PGE2 ) is regarded as a pro-cancer prostanoid, whereas the 1-series (PGE1 ) and the 3-series (PGE3 ) are considered to act as anti-cancer prostanoids. In the present study, we provide possible reasons why PGE1 and PGE3 , but not PGE2 , exert anti-cancer effects by focusing on each diverged E-type prostanoid (EP)4 receptor-mediated signaling pathway. PGE1 , PGE2 and PGE3 function as full agonists in terms of Galphas - and Galphai -protein mediated signaling. However, PGE1 and PGE3 function as partial agonists of T-cell factor (TCF)/beta-catenin (beta-cat)-mediated activity, the well-known cancer related signaling pathway. Furthermore, pretreatment with PGE1 or PGE3 almost completely reduces PGE2 -induced TCF/beta-cat activity. These results provide a plausible reason why PGE1 and PGE3 function as anti-cancer prostanoids as a result of novel biased activity for EP4 receptors. PMID- 28986999 TI - One-step affinity capture and precipitation for improved purification of an industrial monoclonal antibody using Z-ELP functionalized nanocages. AB - Protein A chromatography has been identified as a potential bottleneck in the monoclonal antibody production platform, leading to increased interest in non chromatographic capture technologies. Affinity precipitation using environmentally responsive, Z-domain-elastin-like polypeptide (Z-ELP) fusion proteins has been shown to be a promising alternative. However, elevated temperature and salt concentrations necessary for precipitation resulted in decreased antibody monomer content and reduced purification capacity. To improve upon the existing technology, we reported an enhanced affinity precipitation of antibodies by conjugating Z-ELP to a 25 nm diameter, self-assembled E2 protein nanocage (Z-ELP-E2). The enlarged scale of aggregate formation and IgG-triggered crosslinking through multi-valent binding significantly outperformed traditional Z-ELP-based methods. In the current work, we sought to develop an affinity precipitation process capable of purifying industrial monoclonal antibodies (mAbs) at ambient temperature with minimal added salt. We discovered that the mAb nanocage complex aggregated within 10 min at room temperature without the addition of salt due to the enhanced multi-valent cross-linking. After precipitating out of solution, the complex remained insoluble under all wash buffers tested, and only resolubilized after a low pH elution. Through optimization of key process steps, the affinity precipitation yield and impurity clearance met or exceeded protein A chromatography performance with 95% yield, 3.7 logs host cell protein reduction, and >5 logs of DNA reduction from mAb cell culture. Because of the operational flexibility afforded by this one-step affinity capture and precipitation process, the Z-ELP-E2 based approach has the potential to be a viable alternative to platform mAb purification. PMID- 28987001 TI - Impact of carbon monoxide partial pressures on methanogenesis and medium chain fatty acids production during ethanol fermentation. AB - Medium-chain fatty acids (MCFA) are important biofuel precursors. Carbon monoxide (CO) is a sustainable electron and carbon donor for fatty acid elongation, since it is metabolized to MCFA precursors, it is toxic to most methanogens, and it is a waste product generated in the gasification of waste biomass. The main objective of this work was to determine if the inhibition of methanogenesis through the continuous addition of CO would lead to increased acetate or MCFA production during fermentation of ethanol. The effects of CO partial pressures (PCO ; 0.08-0.3 atm) on methanogenesis, fatty acids production, and the associated microbial communities were studied in batch cultures fed with CO and ethanol. Methanogenesis was partially inhibited at PCO >= 0.11 atm. This inhibition led to increased acetate production during the first phase of fermentation (0-19 days). However, a second addition of ethanol (day 19) triggered MCFA production only at PCO >= 0.11 atm, which probably occurred through the elongation of acetate with CO-derived ethanol and H2 :CO2 . Accordingly, during the second phase of fermentation (days 20-36), the distribution of electrons to acetate decreased at higher PCO , while electrons channeled to MCFA increased. Most probably, Acetobacterium, Clostridium, Pleomorphomonas, Oscillospira, and Blautia metabolized CO to H2 :CO2 , ethanol and/or fatty acids, while Peptostreptococcaceae, Lachnospiraceae, and other Clostridiales utilized these metabolites, along with the provided ethanol, for MCFA production. These results are important for biotechnological systems where fatty acids production are preferred over methanogenesis, such as in chain elongation systems and microbial fuel cells. PMID- 28987002 TI - Bone Turnover in Young Adult Men: Cross-Sectional Determinants and Associations With Prospectively Assessed Bone Loss. AB - Biochemical markers of bone turnover are higher in young adult men than in middle aged men or young adult women. Nonetheless, little is known about the determinants and clinical significance hereof. The present study examined determinants of serum bone turnover markers in men around peak bone mass age, and explored whether bone turnover at this age predicts subsequent changes in bone mass. We used cross-sectional and longitudinal data from 973 and 428 healthy men, respectively, aged 25 to 45 years at baseline, including baseline procollagen type I amino-terminal propeptide (P1NP), osteocalcin, and C-terminal telopeptide of type I collagen (CTX) from fasting serum samples, baseline questionnaire assessed physical activity levels, and baseline and follow-up dual-energy X-ray absorptiometry-derived areal bone mineral density (aBMD) and body composition. Mean follow-up time was 12.4 +/- 0.4 years. At baseline, all bone turnover markers were inversely associated with total body fat mass (beta <= -0.20, p < 0.001), and positively with physical activity during sports activities (beta >= 0.09, p <= 0.003), and, albeit not independently from fat mass, total body lean mass (beta >= 0.20, p <= 0.003). Mean annual aBMD changes in the longitudinal cohort were -0.19% +/- 0.24% at the total body, -0.14% +/- 0.42% at the spine, 0.49% +/- 0.47% at the femoral neck, and -0.25% +/- 0.37% at the total hip (all p < 0.001). Higher bone turnover markers at baseline were associated with larger decreases in aBMD at all measurement sites (beta <= -0.08, p <= 0.081 for P1NP; beta <= -0.16, p <= 0.002 for osteocalcin; and beta <= -0.21, p < 0.001 for CTX). In conclusion, our findings show that sports activities and body composition, primarily fat mass, are the main identified determinants of bone turnover in men around peak bone mass age. Further, bone turnover at this age is an important determinant of subsequent changes in bone mass, with higher levels of bone turnover markers being associated with greater decreases in aBMD. (c) 2017 American Society for Bone and Mineral Research. PMID- 28987000 TI - MicroRNA-126 deficiency enhanced the activation and function of CD4+ T cells by elevating IRS-1 pathway. AB - Recent evidence has shown that microRNA-126 (miR-126) has been involved in the development and function of immune cells, which contributed to the pathogenesis of related clinical diseases. However, the potential role of miR-126 in the development and function of CD4+ T cells remains largely unknown. Here we first found that the activation and proliferation, as well as the expression of interferon (IFN)-gamma, of CD4+ T cells from miR-126 knock-down (KD) mice using the miRNA-sponge technique were enhanced significantly in vitro, compared with those in CD4+ T cells from wild-type (WT) mice. To monitor further the possible effect of miR-126 deficiency on the function of CD4+ T cells in vivo, we used dextran sulphate sodium (DSS)-induced murine model of acute autoimmune colitis and found that miR-126 deficiency could elevate the pathology of colitis. Importantly, the proportion of CD4+ T cells in splenocytes increased significantly in miR-126KD mice. Moreover, the expression levels of CD69 and CD44 on CD4+ T cells increased significantly and the expression level of CD62L decreased significantly. Of note, adoptive cell transfer assay showed that the pathology of colitis was more serious in carboxyfluorescein succinimidyl ester (CFSE)-labelled miR-126KD CD4+ T cell-transferred group, compared with that in the CFSE-labelled WT CD4+ T cells transferred group. Consistently, the expression levels of CD69 and CD44 on CFSE+ cells increased significantly. Furthermore, both the proliferation and IFN-gamma secretion of CFSE+ cells also increased significantly in the CFSE-labelled miR-126KD CD4+ T cell-transferred group. Mechanistic evidence showed that the expression of insulin receptor substrate 1 (IRS-1), as a functional target of miR-126, was elevated in CD4+ T cells from miR 126KD mice, accompanied by altered transduction of the extracellular regulated kinase, protein B (AKT) and nuclear factor kappa B (NF-kappaB) pathway. Our data revealed a novel role in which miR-126 was an intrinsic regulator in the function of CD4+ T cells, which provided preliminary basis for exploring further the role of miR-126 in the development, function of CD4+ T cells and related clinical diseases. PMID- 28987003 TI - RNA-seq analysis of Lgr6+ stem cells and identification of an Lgr6 isoform. AB - We studied Lgr6+ stem cells in experimental UV carcinogenesis in hairless mice. For further characterization through RNA-seq, these stem cells were isolated by FACS from transgenic hairless mice bearing an EGFP-Ires-CreERT2 reporter cassette inserted into exon 1 of the Lgr6 gene (purity confirmed by human ERT2 expression). Between Lgr6/EGFP+ and Lgr6/EGFP- basal cells (Tg/wt), 682 RNAs were differentially expressed, indicating stemness and expression of cancer-related pathways in Lgr6/EGFP+ cells. We discovered that suspected "Lgr6 null" mice (Tg/Tg) expressed RNA of an Lgr6 isoform (delta-Lgr6, lacking 74 N-terminal aa) which could be functional and explain the lack of a phenotype. PMID- 28987004 TI - Molecular Viscosity Sensors with Two Rotators for Optimizing the Fluorescence Intensity-Contrast Trade-Off. AB - A series of fluorescent molecular rotors obtained by introducing two rotational groups ("rotators"), which exhibit different rotational and electron-donating abilities, are discussed. Whereas the control molecular rotor, PH, includes a single rotator (the widely used phenyl group), the PO molecular rotors consist of two rotators (a phenyl group and an alkoxy group), which exhibit simultaneous strongly electron-donating and easy rotational abilities. Compared with the control rotor PH, PO molecular rotors exhibited one order of magnitude higher quantum yield (fluorescence intensity) and simultaneously exhibited significantly higher fluorescence contrast. These properties are directly related to the strong electron-donating ability and low energy barrier of rotation of the alkoxy group, as confirmed by dynamic fluorescence experiments and quantum chemical calculations. The PO molecular rotors exhibited two fluorescence relaxation pathways, whereas the PH molecular rotor exhibited a single fluorescence relaxation pathway. Cellular fluorescence imaging with PO molecular rotors for mapping cellular viscosity was successfully demonstrated. PMID- 28987005 TI - Hybrid asexuality as a primary postzygotic barrier between nascent species: On the interconnection between asexuality, hybridization and speciation. AB - Although sexual reproduction is ubiquitous throughout nature, the molecular machinery behind it has been repeatedly disrupted during evolution, leading to the emergence of asexual lineages in all eukaryotic phyla. Despite intensive research, little is known about what causes the switch from sexual reproduction to asexuality. Interspecific hybridization is one of the candidate explanations, but the reasons for the apparent association between hybridization and asexuality remain unclear. In this study, we combined cross-breeding experiments with population genetic and phylogenomic approaches to reveal the history of speciation and asexuality evolution in European spined loaches (Cobitis). Contemporary species readily hybridize in hybrid zones, but produce infertile males and fertile but clonally reproducing females that cannot mediate introgressions. However, our analysis of exome data indicates that intensive gene flow between species has occurred in the past. Crossings among species with various genetic distances showed that, while distantly related species produced asexual females and sterile males, closely related species produce sexually reproducing hybrids of both sexes. Our results suggest that hybridization leads to sexual hybrids at the initial stages of speciation, but as the species diverge further, the gradual accumulation of reproductive incompatibilities between species could distort their gametogenesis towards asexuality. Interestingly, comparative analysis of published data revealed that hybrid asexuality generally evolves at lower genetic divergences than hybrid sterility or inviability. Given that hybrid asexuality effectively restricts gene flow, it may establish a primary reproductive barrier earlier during diversification than other "classical" forms of postzygotic incompatibilities. Hybrid asexuality may thus indirectly contribute to the speciation process. PMID- 28987007 TI - Honey bee foraging induces upregulation of early growth response protein 1, hormone receptor 38 and candidate downstream genes of the ecdysteroid signalling pathway. AB - In honey bees, continuous foraging at an artificial feeder induced a sustained upregulation of the immediate early genes early growth response protein 1 (Egr-1) and hormone receptor 38 (Hr38). This gene expression response was accompanied by an upregulation of several Egr-1 candidate downstream genes: ecdysone receptor (EcR), dopamine/ecdysteroid receptor (DopEcR), dopamine decarboxylase and dopamine receptor 2. Hr38, EcR and DopEcR are components of the ecdysteroid signalling pathway, which is highly probably involved in learning and memory processes in honey bees and other insects. Time-trained foragers still showed an upregulation of Egr-1 when the feeder was presented at an earlier time of the day, suggesting that the genomic response is more dependent on the food reward than training time. However, presentation of the feeder at the training time without food was still capable of inducing a transient increase in Egr-1 expression. Thus, learnt feeder cues, or even training time, probably affect Egr 1 expression. In contrast, whole brain Egr-1 expression changes did not differ between dancing and nondancing foragers. On the basis of our results we propose that food reward induced continuous foraging ultimately elicits a genomic response involving Egr-1 and Hr38 and their downstream genes. Furthermore this genomic response is highly probably involved in foraging-related learning and memory responses. PMID- 28987006 TI - Effects of assortative mate choice on the genomic and morphological structure of a hybrid zone between two bird subspecies. AB - Phenotypic differentiation plays an important role in the formation and maintenance of reproductive barriers. In some cases, variation in a few key aspects of phenotype can promote and maintain divergence; hence, the identification of these traits and their associations with patterns of genomic divergence is crucial for understanding the patterns and processes of population differentiation. We studied hybridization between the alba and personata subspecies of the white wagtail (Motacilla alba), and quantified divergence and introgression of multiple morphological traits and 19,437 SNP loci on a 3,000 km transect. Our goal was to identify traits that may contribute to reproductive barriers and to assess how variation in these traits corresponds to patterns of genome-wide divergence. Variation in only one trait-head plumage patterning-was consistent with reproductive isolation. Transitions in head plumage were steep and occurred over otherwise morphologically and genetically homogeneous populations, whereas cline centres for other traits and genomic ancestry were displaced over 100 km from the head cline. Field observational data show that social pairs mated assortatively by head plumage, suggesting that these phenotypes are maintained by divergent mating preferences. In contrast, variation in all other traits and genetic markers could be explained by neutral diffusion, although weak ecological selection cannot be ruled out. Our results emphasize that assortative mating may maintain phenotypic differences independent of other processes shaping genome-wide variation, consistent with other recent findings that raise questions about the relative importance of mate choice, ecological selection and selectively neutral processes for divergent evolution. PMID- 28987008 TI - mvmapper: Interactive spatial mapping of genetic structures. AB - Characterizing genetic structure across geographic space is a fundamental challenge in population genetics. Multivariate statistical analyses are powerful tools for summarizing genetic variability, but geographic information and accompanying metadata are not always easily integrated into these methods in a user-friendly fashion. Here, we present a deployable Python-based web-tool, mvmapper, for visualizing and exploring results of multivariate analyses in geographic space. This tool can be used to map results of virtually any multivariate analysis of georeferenced data, and routines for exporting results from a number of standard methods have been integrated in the R package adegenet, including principal components analysis (PCA), spatial PCA, discriminant analysis of principal components, principal coordinates analysis, nonmetric dimensional scaling and correspondence analysis. mvmapper's greatest strength is facilitating dynamic and interactive exploration of the statistical and geographic frameworks side by side, a task that is difficult and time-consuming with currently available tools. Source code and deployment instructions, as well as a link to a hosted instance of mvmapper, can be found at https://popphylotools.github.io/mvMapper/. PMID- 28987010 TI - Precise carbon isotopic ratio analyses of micro amounts of carbonate and non carbonate in basalt using continuous-flow isotope ratio mass spectrometry. AB - RATIONALE: Continuous-flow isotope ratio mass spectrometry (CF-IRMS) is a specialized technique used to quickly analyze very small amounts of sample. We have used CF-IRMS to assess the influences of sample weight and relative carbon content on the accuracy and precision of the delta13 C values of micro amounts of carbonate and non-carbonate in silicate rocks. METHODS: The analytical work was performed on a Gasbench II (GB) sample preparation device and on an Elemental Analyzer (EA), which were both interfaced to CF-IRMS instruments. Potential silicate matrix effects on the carbon isotopic analyses were investigated by measuring mixtures of calibrated carbon reference materials and quartz powder. The calibration lines, established by the measured raw values and the known values of three reference materials mixed with quartz powder, were used to calibrate the delta13 C values of basalt samples from eastern China. RESULTS: The delta13 C values measured by GB-CF-IRMS of one national carbonate reference material, GBW04416, deviate slightly from the known value for approximately 20-70 MUg of carbonate contained in 4.5-mL vials; the smaller the sample size, the lower the measured delta13 C values. External precision better than 0.10/00 (1sigma, n = 26) is achieved at a signal intensity for mass 44 of between 868 and 1614 mV, corresponding to a sample weight of 30.8-50.2 MUg, whereas it is reduced to 0.270/00 (1sigma, n = 34) at a signal intensity between 519 and 1614 mV, corresponding to a sample weight of 21.1-50.2 MUg. In the EA-CF-IRMS experiments for non-carbonate carbon, at high carbon concentration (greater than 800 ppm) and at optimum sample weights, the accuracy and precision are both better than 0.20/00. For carbon concentrations less than 500 ppm, the measured delta13 C values deviate from the average by up to -1.20/00 and the precision is 0.740/00. CONCLUSIONS: The measured delta13 C values decrease substantially at lower carbon concentration and higher sample weights, and poorer precision is obtained. Suggestions are made to measure repeatedly the same carbon concentration of sample and reference materials in order to obtain not only reproducible, but also accurate carbon isotope ratios. PMID- 28987009 TI - Native Chemical Ligation Directed by Photocleavable Peptide Nucleic Acid (PNA) Templates. AB - A novel peptide-peptide ligation strategy is introduced that has the potential to provide peptide libraries of linearly or branched coupled fragments and will be suited to introduce simultaneous protein modifications at different ligation sites. Ligation is assisted by templating peptide nucleic acid (PNA) strands, and therefore, ligation specificity is solely encoded by the PNA sequence. PNA templating, in general, allows for various kinds of covalent ligation reactions. As a proof of principle, a native chemical ligation strategy was elaborated. This PNA-templated ligation includes easy on-resin procedures to couple linkers and PNA to the respective peptides, and a traceless photocleavage of the linker/PNA oligomer after the ligation step. A 4,5-dimethoxy-2-nitrobenzaldehyde-based linker that allowed the photocleavable linkage of two bio-oligomers was developed. PMID- 28987011 TI - The Distant Double Bond Determines the Fate of the Carboxylic Group in the Dissociative Photoionization of Oleic Acid. AB - The valence threshold photoionization of oleic acid has been studied using synchrotron VUV radiation and imaging photoelectron photoion coincidence (iPEPICO) spectroscopy. An oleic acid aerosol beam was impacted on a copper thermodesorber, heated to 130 degrees C, to evaporate the particles quantitatively. Upon threshold photoionization, oleic acid produces the intact parent ion first, followed by dehydration at higher energies. Starting at ca. 10 eV, a large number of fragment ions slowly rise suggesting several fragmentation coordinates with quasi-degenerate activation energies. However, water loss is the dominant low-energy dissociation channel, and it is shown to be closely related to the unsaturated carbon chain. In the lowest-barrier process, one of the four allylic hydrogen atoms is transferred to the carboxyl group to form the leaving water molecule and a cyclic ketone fragment ion. A statistical model to analyze the breakdown diagram and measured rate constants yields a 0 K appearance energy of 9.77 eV, which can be compared with the density functional theory result of 9.19 eV. Alternative H-transfer steps yielding a terminal C=O group are ruled out based on energetics and kinetics arguments. Some of the previous photoionization mass spectrometric studies also reported 2 amu and 26 amu loss fragment ions, corresponding to hydrogen and acetylene loss. We could not identify such peaks in the mass spectrum of oleic acid. PMID- 28987012 TI - Predicting post-hepatectomy liver failure by combined volumetric, functional MR image and laboratory analysis. AB - BACKGROUND & AIMS: To assess the efficacy of functional MR image with volumetric, liver function test and indocyanine green clearance (ICG) in identifying the patients who are at risk of post-hepatectomy liver failure (PHLF). METHODS: We retrospectively included 115 patients undergoing gadoxetic acid-enhanced MR imaging before hepatectomy at one medical centre from January 2013 to December 2015. Contrast enhancement ratio (CER) between transitional and hepatobiliary phases (3 and 30 minutes post-contrast) was calculated. Total liver volume (TLV) and spleen volume (Sp) were measured. Post-operatively, the histological Ishak fibrosis score was collected. Potential risk factors for liver failure were analysed, and the performance was examined by receiver operating characteristic curve. RESULTS: Post-hepatectomy liver failure (PHLF) occurred in 16 patients (13.9%). TLV/SLV, ADC value, CERHBP/TP and total liver contrast enhancement ratio (tCER) were associated with PHLF (P < .05). Between PHLF and non-PHLF groups, remnant liver volume (RLV), RLV/SLV, Sp/RLV, remnant liver contrast enhancement ratio (rCER) and Ishak fibrosis score showed statistical difference. rCER showed superiority in diagnostic performance (AUC = 0.78) with the optimal cut-off value of 1.23. CONCLUSIONS: Gadoxetic acid-enhanced MR imaging with volumetric is a reliable method for evaluating functional liver volume and determining the risk of PHLF. PMID- 28987013 TI - Trends in age of smoking initiation in the Netherlands: a shift towards older ages? AB - BACKGROUND AND AIM: As smoking initiation generally occurs in adolescence, smoking prevention is targeted primarily at young adolescents (aged below 16 years). We hypothesize that, with the adoption of increasingly stronger youth access laws, a shift in the age of smoking initiation may have occurred. DESIGN: Repeated cross-sectional survey. SETTING: The Netherlands. PARTICIPANTS: A total of 13 163 respondents born between 1980 and 1995. MEASUREMENTS: In the 2010-15 National Health Survey we measured retrospectively self-reported initiation rates per year of age by birth cohort (1980-83, 1984-87, 1988-91, 1992-95). Logistic regression analyses were performed to assess differences between cohorts, per sex and educational level. FINDINGS: Of those who started smoking, 67.2% initiated smoking between 12 and 16 years of age. Contrary to our hypothesis, no shift in initiation towards higher ages was observed. The peak age of initiation was 16 years for all cohorts. Initiation at ages 17-21 was lower in younger birth cohorts than in older birth cohorts [e.g. cohort 1993-95 versus 1980-83: odds ratio (OR) for initiating at 19-21 years = 0.45, 95% confidence interval (CI) = 0.31-0.64]. Trends in age of initiation were similar for males and females. Initiation at ages 15-17 decreased across cohorts for respondents in higher education levels, but not for those in lower education levels. CONCLUSIONS: In the Netherlands, the peak age of smoking initiation did not shift throughour subsequent cohorts born between 1980 and 1995, suggesting that young adolescents remain the main target group for smoking initiation prevention policies. PMID- 28987014 TI - Adhesion, unfolding forces, and molecular elasticity of fibronectin coatings: An atomic force microscopy study. AB - Fibronectin is an extracellular matrix protein that is involved in cell adhesion, growth, migration, differentiation, and wound healing. Fibronectin coatings are currently used in many laboratories for biomedical and biotechnology purposes. In this study we have investigated the adhesion and mechanical properties of fibronectin coatings. The coatings were also used to study the role of the residence time and the influence of the loading rate in nonspecific interactions. The results showed that the adhesion force between silica and fibronectin increased with loading rate delivering similar values for residence times of 1 and 2 s. Further analysis indicated that the distance to the transition state was about 0.5 nm. Moreover, the adhesion force did not vary with the loading rate for contact time of 0 s. The unfolding of fibronectin domains also depended of the Dwell time (no unfolding events were observed for zero residence time). Applied loads of 2 nN were able to stretch the fibronectin layer up to 200 nm and to unfold the three fibronectin domains, which were similar for a Dwell time of 1 and 2 s. However, the unfolding length increased with loading rate: below 2.5 um s-1 the obtained lengths matched the value of FN I (13.5 nm), while for higher speeds the measured values corresponded to the lengths of FN II (18 nm) and FN III (27 nm). This investigation has answered and opened new questions about the mechanical stability and function of fibronectin coatings. The results have also raised theoretical questions about the difference between specific and nonspecific interactions to be addressed in future work. PMID- 28987016 TI - Sensitivity of aspiration as a safety test before injection of soft tissue fillers. AB - BACKGROUND: Embolism due to accidental intra-arterial injection of a soft tissue filler (STF) can lead to serious complications. Physicians practice aspiration as a safety test before injection to rule out intra-arterial placement of the needle tip. The value of aspiration as a safety test is evaluated in this study, which also considered the rheological properties of different STFs and their needle dimensions. METHODS: Aspiration with eleven different needle sizes and 24 different STFs was performed using Ringer's lactate (RL) colored with blue skin marking ink and secondly an empty saline bag containing anticoagulated blood, both pressurized to 150 mm Hg to mimic arterial blood pressure. Time between the start of aspiration and liquid in the needle hub was recorded. RESULTS: A total of 340 individual aspiration tests with different STFs and needles were performed, of which 112 yielded true-positive results within 1-s and 128 yielded false-negative results after 10 s. Positive results between one and ten seconds were seen in 101 aspiration tests. CONCLUSIONS: True-positive results were seen in 33% of the tests performed with STFs within 1 s of aspiration. Aspiration test results are influenced by needle diameter, needle length, and rheological properties of STFs. Additional safety measures are necessary to further reduce risk of inadvertent intravascular injection of STFs. PMID- 28987015 TI - Center practice drives variation in choice of US kidney transplant induction therapy: a retrospective analysis of contemporary practice. AB - To assess factors that influence the choice of induction regimen in contemporary kidney transplantation, we examined center-identified, national transplant registry data for 166 776 US recipients (2005-2014). Bilevel hierarchical models were constructed, wherein use of each regimen was compared pairwise with use of interleukin-2 receptor blocking antibodies (IL2rAb). Overall, 82% of patients received induction, including thymoglobulin (TMG, 46%), IL2rAb (22%), alemtuzumab (ALEM, 13%), and other agents (1%). However, proportions of patients receiving induction varied widely across centers (0-100%). Recipients of living donor transplants and self-pay patients were less likely to receive induction treatment. Clinical factors associated with use of TMG or ALEM (vs. IL2rAb) included age, black race, sensitization, retransplant status, nonstandard deceased donor, and delayed graft function. However, these characteristics explained only 10-33% of observed variation. Based on intraclass correlation analysis, "center effect" explained most of the variation in TMG (58%), ALEM (66%), other (51%), and no induction (58%) use. Median odds ratios generated from case-factor adjusted models (7.66-11.19) also supported large differences in the likelihood of induction choices between centers. The wide variation in induction therapy choice across US transplant centers is not dominantly explained by differences in patient or donor characteristics; rather, it reflects center choice and practice. PMID- 28987017 TI - Temperature-dependent Henry's Law constants of 4-alkyl branched-chain fatty acids and 3-methylindole in an oil-air matrix and analysis of volatiles in lamb fat using selected ion flow tube mass spectrometry. AB - RATIONALE: 4-Alkyl branched-chain fatty acids and 3-methylindole are characteristic flavor compounds associated with sheep meat. Determining their partitioning behavior between the gas and condensed phase and ultimately developing a correlation between the compound's headspace concentration and sensory descriptive grouping are important for high-throughput characterization and grading classification. METHODS: The headspace concentrations of 3 methylindole, 4-methyloctanoic acid, 4-ethyl-octanoic acid, and 4-methylnonanoic acid above corn-oil-based standard solutions and lamb fat samples were measured using selected ion flow tube-mass spectrometry (SIFT-MS). The standard solutions were equilibrated at 80, 100, 110 and 125 degrees C while the fat samples were equilibrated at 125 degrees C. Statistical evaluation, linear and polynomial regression analyses were performed to establish the compound-specific and temperature-dependent Henry's Law constants, enthalpy (DeltaH) and entropy (DeltaS) of phase changes. RESULTS: The Henry's Law constants (kHcp ) were calculated from the regression analysis with a high degree of confidence (p < 0.05) and linearity (r2 > 0.99). The kHcp increased with increase in equilibrium temperature. The empirical calculation of DeltaH and DeltaS at different temperatures confirmed the temperature-dependence of the Henry's Law constants. The headspace concentrations of the lamb-flavor compounds were determined above actual lamb fat samples and the corresponding condensed-phase concentrations were successfully derived. CONCLUSIONS: The temperature-dependent Henry's Law constants, DeltaH, and DeltaS of phase changes for 3-methylindole, 4 methyloctanoic acid, 4-ethyloctanoic acid, and 4-methylnonanoic acid in an air oil matrix were empirically derived. The effectiveness of SIFT-MS for the direct, real-time, and rapid determination of key flavor compounds in lamb fat samples was established. PMID- 28987018 TI - Validation of multi-frequency bioelectrical impedance analysis versus dual-energy X-ray absorptiometry to measure body fat percentage in overweight/obese Colombian adults. AB - OBJECTIVES: To verify the validity of multi-frequency bioelectrical impedance analysis (mBCA) for predicting body fat percentage (BF%) in overweight/obese adults using dual-energy X-ray absorptiometry (DXA) as the reference method. METHODS: Forty-eight adults participated (54% women, mean age = 41.0 +/- 7.3 years old). The Pearson's correlation coefficient was used to evaluate the correlation between BIA and BF% assessed by DXA. The concordance between BF% measured by both methods was obtained with Lin's concordance correlation coefficient and Bland-Altman difference plots. RESULTS: Measures of BF% were estimated as 39.0 (SD = 6.1) and 38.3 (SD = 6.5) using DXA and mBCA, respectively. The Pearson's correlation coefficient reflected a strong correlation (r =.921, P = .001). The paired t-test showed a significant mean difference between these methods for obese men BF% of -0.6 [(SD 1.95; 95% CI = 4.0 to 3.0), P =.037]. Overall, the bias of the mBCA was -0.6 [(SD 2.2; 95% CI = 5.0 to 3.7), P =.041], which indicated that the mBCA method significantly underestimated BF% in comparison to the reference method. Finally, in both genders, Lin's concordance correlation coefficient showed a strong agreement. More specifically the DXA value was rhoc = 0.943 (95% CI = 0.775 to 0.950) and the mBCA value was rhoc = 0.948 (95% CI = 0.778 to 0.978). CONCLUSIONS: Our analysis showed a strong agreement between the two methods as reflected in the range of BF%. These results show that mBCA and DXA are comparable methods for measuring body composition with higher body fat percentages. However, due to broad limits of agreement, we can only recommend mBCA for groups of populations. PMID- 28987019 TI - Patterns of substance use and mortality risk in a cohort of 'hard-to-reach' polysubstance users. AB - AIMS: To examine the mortality risk in a cohort of 'hard-to-reach' polysubstance users and its putative associations with substance use. Specifically, we estimated all-cause mortality risk as a function of individual substance use indicators, and then as a function of their complex, 'real-life' patterns as identified through latent class analysis (LCA). DESIGN: Prospective cohort study among street- and low-threshold service-recruited polysubstance users included between September and November 2013 and followed through the National Cause of Death Registry until 31 October 2015. SETTING: Seven Norwegian cities. PARTICIPANTS: A total of 884 users of illegal opioids and/or stimulants. Of these, 357 were in opioid substitution treatment (OST) at the time of inclusion. Forty-four participants died during follow-up. MEASUREMENTS: Primary outcome: all cause mortality risk. Unadjusted and adjusted Cox proportional hazard (PH) regression models (covariates: male, age, homelessness/shelter use, overdose experience, OST status, years of injecting, individual substance use indicators, city, use patterns). LCA models estimated separately for those in and those not in OST due to measurement invariance. FINDINGS: The crude mortality rate was 2.52 per 100 person-years. Standardized mortality ratio was 26.11 [95% confidence interval (CI) = 10.06-54.87] for women and 10.71 (95% CI = 6.39-16.81) for men. No single drug use indicator, such as 'heroin injection' or 'number of drugs used', was associated with the mortality risk. However, meaningful use patterns were identified; three OST and non-OST patterns each. The non-OST patterns 'polysubstance injectors' [hazard ratio (HR) = 3.45, 95% CI = 0.98-12.14] and 'low frequent injectors' (HR = 3.17, CI = 1.05-9.56) were associated significantly with the mortality risk even when adjusted for other known risk factors. CONCLUSIONS: In a Norwegian prospective cohort study, 'hard-to-reach' polysubstance users had a more than 10 times higher mortality risk than the general population. Mortality risk was not a function of any single drug use indicator, but two distinct combinations of substances, frequencies and routes of administration were associated with the mortality risk. PMID- 28987020 TI - Cardiac and haemodynamic influence on carotid artery longitudinal wall motion. AB - NEW FINDINGS: What is the central question of this study? Carotid artery longitudinal wall motion (CALM) is a bidirectional forward and backward motion of the arterial wall; however, there is no evidence in humans for what controls CALM despite proposals for pulse pressure, left ventricular motion and shear rate. What is the main finding and its importance? Carotid artery longitudinal wall motion responses were heterogeneous when manipulating sympathetic activation and endothelium-independent vasodilatation, leading to non-significant group responses. However, individual CALM responses were associated with left ventricular rotation and shear rate. These findings are important when interpreting changes in CALM in humans with acute or chronic experimental designs. Carotid artery longitudinal wall motion (CALM) has recently attracted interest as an indicator of arterial health; however, the regulation of CALM is poorly understood. We conducted a series of studies aimed at manipulating pulse pressure (PP), left ventricular (LV) motion and carotid shear rate, which have been previously suggested to regulate various components of CALM pattern and magnitude. To determine the regulatory influences on CALM, 15 healthy men (22 +/- 2 years old) were exposed to three acute interventions: the serial subtraction test (SST); the cold pressor test (CPT); and exposure to sublingual nitroglycerine (NTG). The SST elicited increases in PP (P < 0.01), apical LV rotation (P < 0.01) and carotid shear rate (P < 0.01), with no changes in CALM (P > 0.05). Likewise, the CPT elicited increases in PP (P = 0.01), basal LV rotation (P = 0.04) and carotid shear rate (P = 0.01), with no changes in CALM (P > 0.05). Conversely, exposure to NTG elicited no change in PP (P = 0.22), basal (P = 0.65) or apical LV rotation (P = 0.45), but did decrease carotid shear rate (P < 0.01), without altering CALM (P > 0.05). Considerable individual variability in CALM responses prompted further analyses where all three interventions were pooled for change scores. Changes in LV basal rotation were related to changes in systolic retrograde CALM (B = -0.025, P = 0.03), whereas changes in carotid shear rate were related to changes in diastolic CALM displacement (B = 0.0009, P = 0.01). The interventions were underpinned by relationships between CALM and both LV basal rotation and local shear rate at the individual level, indicating that cardiac and haemodynamic factors may influence CALM in humans. PMID- 28987021 TI - Computer-aided diagnosis software for vulvovaginal candidiasis detection from Pap smear images. AB - Vulvovaginal candidiasis (VVC) is a common gynecologic infection and it occurs when there is overgrowth of the yeast called Candida. VVC diagnosis is usually done by observing a Pap smear sample under a microscope and searching for the conidium and mycelium components of Candida. This manual method is time consuming, subjective and tedious. Any diagnosis tools that detect VVC, semi- or full-automatically, can be very helpful to pathologists. This article presents a computer aided diagnosis (CAD) software to improve human diagnosis of VVC from Pap smear samples. The proposed software is designed based on phenotypic and morphology features of the Candida in Pap smear sample images. This software provide a user-friendly interface which consists of a set of image processing tools and analytical results that helps to detect Candida and determine severity of illness. The software was evaluated on 200 Pap smear sample images and obtained specificity of 91.04% and sensitivity of 92.48% to detect VVC. As a result, the use of the proposed software reduces diagnostic time and can be employed as a second objective opinion for pathologists. PMID- 28987022 TI - Debate on "Defining melancholia: A core mood disorder". PMID- 28987023 TI - Efficacy and safety of a novel, soluble microneedle patch for the improvement of facial wrinkle. AB - BACKGROUND: Various kinds of functional cosmetics are on the market, although there are a variety of opinions concerning the actual effect. Transdermal microneedle patch has been introduced as a newly developed device for drug delivery through the skin. OBJECTIVE: This study was conducted to verify the face skin improvement effect and safety of a novel cosmetic microneedle patch. METHODS: A total of 84 Korean females finished this prospective clinical trial. The subjects were divided into 3 groups: (1) soluble hyaluronic acid (HA) microneedle patch alone, (2) soluble HA microneedle patch plus adenosine wrinkle cream, and (3) adenosine wrinkle cream alone. The treatments were applied to the crow's feet and nasolabial fold wrinkle for 12 weeks. The test areas were measured before treatment and at 4, 8, and 12 weeks after use of the test product. At the completion of the testing period of the trial, the global assessment of efficacy and product preferences were surveyed from the subjects. RESULTS: Combination treatment with wrinkle cream and microneedle patch significantly improved Merz scale for crow's feet and nasolabial folds, compared to the sole application of wrinkle cream or patch. Measurement on the crow's feet showed an overall improvement in all 3 groups, yielding no significant differences among the groups. No serious adverse effects were observed during the follow-up period. CONCLUSION: Combination application of a soluble microneedle patch and wrinkle cream was an effective treatment in improving facial wrinkles, thus enhancing skin rejuvenation. PMID- 28987024 TI - Urban landscapes can change virus gene flow and evolution in a fragmentation sensitive carnivore. AB - Urban expansion has widespread impacts on wildlife species globally, including the transmission and emergence of infectious diseases. However, there is almost no information about how urban landscapes shape transmission dynamics in wildlife. Using an innovative phylodynamic approach combining host and pathogen molecular data with landscape characteristics and host traits, we untangle the complex factors that drive transmission networks of feline immunodeficiency virus (FIV) in bobcats (Lynx rufus). We found that the urban landscape played a significant role in shaping FIV transmission. Even though bobcats were often trapped within the urban matrix, FIV transmission events were more likely to occur in areas with more natural habitat elements. Urban fragmentation also resulted in lower rates of pathogen evolution, possibly owing to a narrower range of host genotypes in the fragmented area. Combined, our findings show that urban landscapes can have impacts on a pathogen and its evolution in a carnivore living in one of the most fragmented and urban systems in North America. The analytical approach used here can be broadly applied to other host-pathogen systems, including humans. PMID- 28987025 TI - An Integrated Bioprocess for the Expansion and Chondrogenic Priming of Human Periosteum-Derived Progenitor Cells in Suspension Bioreactors. AB - The increasing use of microcarrier-based suspension bioreactors for scalable expansion of adult progenitor cells in recent years reveals the necessity of such approaches to address bio manufacturing challenges of advanced therapeutic medicinal products. However, the differentiation of progenitor cells within suspension bioreactors for the production of tissue modules is of equal importance but not well investigated. This study reports on the development of a bioreactor-based integrated process for expansion and chondrogenic priming of human periosteum-derived stem cells (hPDCs) using Cultispher S microcarriers. Spinner flask-based expansion and priming of hPDCs were carried out over 12 days for expansion and 14 days for priming. Characterization of the cells were carried out every 3rd day. Our study showed that hPDCs were able to expand till confluency with fold increase of 3.2+/-0.64 and to be subsequently primed toward a chondrogenic state within spinner flasks. During expansion, the cells maintained their phenotypic markers, trilineage differentiation capabilities and viability. Upon switching to TGF-beta containing media the cells were able to differentiate toward chondrogenic lineage by clustering into mm-sized macrotissues containing hundreds of microcarriers. Chondrogenic priming was further evidenced by the expression of relevant markers at the mRNA level while maintaining their viability. Ectopic implantation of macrotissues highlighted that they were able to sustain their chondrogenic properties for 8 weeks in vivo. The method indicated here, suggests that expansion and relevant priming of progenitor cells can be carried out in an integrated bioprocess using spinner flasks and as such could be potentially extrapolated to other stem and progenitor cell populations. PMID- 28987026 TI - The micromorphological characterization of adhesive bond in dentin different locations. AB - The aim of this study was to analyse the interfacial micromorphology of total etch adhesives and dentin structures different locations by using SEM. Standardized cylindrical cavities (3mm in diameter, 2mm deep) with all margins in dentin were prepared on occlusal and buccal surfaces of twenty extracted human third molars. A total-etch dentin adhesive system and a light-cure flowable composite (Filtek Ultimate Flowable, 3M ESPE, St. Paul, MN, USA) were used in this study. Micro-morphological SEM analysis of the marginal seal of the original tooth specimens was performed using high magnification of up to 1000*. In this study, we found the difference in interfacial micromorphology in dentin different locations. Also, marginal gap was found in both observed dentin area. Better understanding of complexity and three- dimensional variations of the tooth structure is important for prevention of clinical challenges such as postoperative sensitivity, marginal discoloration and secondary caries, which could be prevented by achieving of predictable and long-lasting adhesive bond. PMID- 28987027 TI - Formation of oxidative and non-oxidative dimers in metallothioneins: Implications for charge-state analysis for structural determination. AB - RATIONALE: Metallothioneins (MTs) are a class of dynamic proteins that have been investigated extensively using mass spectrometric methods due to their amenability to ionization. Here we detect the formation of oxidative and non oxidative MT dimers using high-resolution mass spectrometry (HRMS) which has previously been overlooked with lower-resolution techniques. METHODS: Recombinant human MT1a and its isolated domain fragments were analyzed by high-resolution Thermo Q-Exactive and Bruker time-of-flight (TOF) mass spectrometers. Covalent Cys modification was performed using N-ethylmalemide to probe the effect of Cys oxidation on dimer formation. RESULTS: Dimerization was detected in the analysis of select charge states of Zn7 MT and apo-betaMT. Specifically, high resolution (140 k) revealed the +6 dimer peaks overlapping with the +3 charge state, but not with the other charge states (+4, +5, +6). The proteins with covalently modified Cys did not show dimer formation in any of their charge states. Apo-alpha and apo betaalphaMT also did not form dimers under the conditions tested. CONCLUSIONS: Dimerization of MT was detected for zinc metalated and certain apo-MT forms with HRMS, which was not seen with lower-resolution techniques. These dimers appear overlapped only with certain charge states, confounding their analysis for structural characterization of MTs. The Zn-MT dimers appeared to be non oxidative; however, the formation of dimers in the apo-protein is likely dependent on Cys oxidation. PMID- 28987028 TI - Fuel-reduction management alters plant composition, carbon and nitrogen pools, and soil thaw in Alaskan boreal forest. AB - Increasing wildfire activity in Alaska's boreal forests has led to greater fuel reduction management. Management has been implemented to reduce wildfire spread, but the ecological impacts of these practices are poorly known. We quantified the effects of hand-thinning and shearblading on above- and belowground stand characteristics, plant species composition, carbon (C) and nitrogen (N) pools, and soil thaw across 19 sites dominated by black spruce (Picea mariana) in interior Alaska treated 2-12 years prior to sampling. The density of deciduous tree seedlings was significantly higher in shearbladed areas compared to unmanaged forest (6.4 vs. 0.1 stems/m2 ), and unmanaged stands exhibited the highest mean density of conifer seedlings and layers (1.4 stems/m2 ). Understory plant community composition was most similar between unmanaged and thinned stands. Shearblading resulted in a near complete loss of aboveground tree biomass C pools while thinning approximately halved the C pool size (1.2 kg C/m2 compared to 3.1 kg C/m2 in unmanaged forest). Significantly smaller soil organic layer (SOL) C and N pools were observed in shearbladed stands (3.2 kg C/m2 and 116.8 g N/m2 ) relative to thinned (6.0 kg C/m2 and 192.2 g N/m2 ) and unmanaged (5.9 kg C/m2 and 178.7 g N/m2 ) stands. No difference in C and N pool sizes in the uppermost 10 cm of mineral soil was observed among stand types. Total C stocks for measured pools was 2.6 kg C/m2 smaller in thinned stands and 5.8 kg C/m2 smaller in shearbladed stands when compared to unmanaged forest. Soil thaw depth averaged 13 cm deeper in thinned areas and 46 cm deeper in shearbladed areas relative to adjacent unmanaged stands, although variability was high across sites. Deeper soil thaw was linked to shallower SOL depth for unmanaged stands and both management types, however for any given SOL depth, thaw tended to be deeper in shearbladed areas compared to unmanaged forest. These findings indicate that fuel-reduction management alters plant community composition, C and N pools, and soil thaw depth, with consequences for ecosystem structure and function beyond those intended for fire management. PMID- 28987029 TI - Adsorption Behavior of Charge Isoforms of Monoclonal Antibodies on Strong Cation Exchangers. AB - In this work, the adsorption behavior of the different charge isoforms of the same monoclonal antibody (mAb) on strong cation-exchange resins is analyzed. While charge isoforms of the same antibody mainly differ in their effective charge, the similar structure and size allows developing a simplified model, which describes the adsorption behavior of mAb charge isoforms independently of the number of isoforms with only four parameters. In contrast to classical model based descriptions of the adsorption isotherm, the proposed work enables retrieving some physical meaning in the definition of the model parameters. These model parameters are determined for several resin-antibody combinations. Thereby it is found that for mAbs on commercial cation exchangers an effective resin charge density of 0.22 +/- 0.08 mmol mL-1 of solid phase is used for protein binding, which was found to be independent of the absolute resin charge density measured by titration. The presented results help to understand the adsorption behavior of mAbs on cation-exchangers, which is applicable both for the isolation of the main charge isoform or for preserving a certain charge isoform pattern during the polishing processes. PMID- 28987031 TI - Using minimalist self-assembling peptides as hierarchical scaffolds to stabilise growth factors and promote stem cell integration in the injured brain. AB - Neurotrophic growth factors are effective in slowing progressive degeneration and/or promoting neural repair through the support of residual host and/or transplanted neurons. However, limitations including short half-life and enzyme susceptibility of growth factors highlight the need for alternative strategies to prolong localised delivery at a site of injury. Here, we establish the utility of minimalist N-fluorenylmethyloxycarbonyl (Fmoc) self-assembling peptides (SAPs) as growth factor delivery vehicle, targeted at supporting neural transplants in an animal model of Parkinson's disease. The neural tissue-specific SAP, Fmoc-DIKVAV, demonstrated sustained release of glial cell line derived neurotrophic factor, up to 172 hr after gel loading. This represents a significant advance in drug delivery, because its lifetime in phosphate buffered saline was less than 1 hr. In vivo transplantation of neural progenitor cells, together with our growth factor-loaded material, into the injured brain improved graft survival compared with cell transplants alone. We show for the first time the use of minimalist Fmoc-SAP in an in vivo disease model for sustaining the delivery of neurotrophic growth factors, facilitating their spatial and temporal delivery in vivo, whilst also providing an enhanced niche environment for transplanted cells. PMID- 28987032 TI - Functionalized PVA-silk blended nanofibrous mats promote diabetic wound healing via regulation of extracellular matrix and tissue remodelling. AB - Chronic cutaneous ulcers, a complex pathophysiological diabetic condition, represent a critical clinical challenge in the current diabetes mellitus pandemic. Consequently, there is a compelling need for bioactive dressings that can trigger healing processes for complete wound repair. Silk fibroin (SF), a natural protein polymer from mulberry and non-mulberry silkworms, has properties that support accelerated wound healing rate. SF from non-mulberry variety possesses additional cell-binding motifs (arginine, glycine, and aspartate), offering cell-material interactions. This study is aimed to investigate wound healing efficacy of dressings made up of various SF varieties blended with poly(vinyl alcohol) biopolymer in alloxan-induced diabetic rabbit model. The nanofibrous mats have been developed using electrospinning and functionalized with growth factors and LL-37 antimicrobial peptide for sustained delivery. Following post 14-day treatment, non-mulberry SF (NMSF)-based dressings healed the wounds faster, in comparison with their mulberry Bombyx mori SF, poly(vinyl alcohol), and control counterparts (p < .01). NMSF-based dressings also supported faster granulation tissue development, angiogenesis, and reepithelialization of wounds. Gene expression study of matrix metalloproteinases and collagen proteins affirmed higher extent of tissue remodelling during the repair process. Furthermore, there was organized extracellular matrix deposition (collagen type I, collagen type III, elastin, and reticulin) and higher wound breaking strength in NMSF compared with other groups after 4 weeks. These results validated the potential of NMSF-based bioactive dressings to regulate extracellular matrix deposition leading to faster and complete repair of chronic diabetic cutaneous wounds. PMID- 28987030 TI - Identifying HIPK1 as Target of miR-22-3p Enhancing Recombinant Protein Production From HEK 293 Cell by Using Microarray and HTP siRNA Screen. AB - Protein expression from human embryonic kidney cells (HEK 293) is an important tool for structural and clinical studies. It is previously shown that microRNAs (small, noncoding RNAs) are effective means for improved protein expression from these cells, and by conducting a high-throughput screening of the human microRNA library, several microRNAs are identified as potential candidates for improving expression. From these, miR-22-3p is chosen for further study since it increased the expression of luciferase, two membrane proteins and a secreted fusion protein with minimal effect on the cells' growth and viability. Since each microRNA can interact with several gene targets, it is of interest to identify the repressed genes for understanding and exploring the improved expression mechanism for further implementation. Here, the authors describe a novel approach for identification of the target genes by integrating the differential gene expression analysis with information obtained from our previously conducted high throughput siRNA screening. The identified genes were validated as being involved in improving luciferase expression by using siRNA and qRT-PCR. Repressing the target gene, HIPK1, is found to increase luciferase and GPC3 expression 3.3- and 2.2-fold, respectively. PMID- 28987033 TI - TREM2 expression in the human brain: a marker of monocyte recruitment? AB - Mutation in the triggering receptor expressed on myeloid cells (TREM) 2 gene has been identified as a risk factor for several neurodegenerative diseases including Alzheimer's disease (AD). Experimental studies using animal models of AD have highlighted a number of functions associated with TREM2 and its expression by microglial cells. It has therefore been assumed that this is also the case in humans. However, there is very limited information concerning the cellular expression of TREM2 in the human brain. As part of investigations of microglia using post-mortem resources provided by the Medical Research Council Cognitive Function and Ageing Studies (MRC-CFAS), we immunostained the cerebral cortex of 299 participants for TREM2 using the Sigma antibody HPA010917 and compared with the macrophage/microglial markers Iba1 and CD68. As expected, Iba1 and CD68 labeled microglia and perivascular macrophages. However, in most cases (284/299), the TREM2 antibody labelled monocytes within vascular lumens, but not microglia or perivascular macrophages. In contrast, in 5 out of 6 cases with acute infarcts, TREM2 immunoreaction identified cells within the brain parenchyma interpreted as recruited monocytes. Six cases with old infarcts contained phagocytic foamy macrophages which were CD68-positive but TREM2 negative. Our observations, using the HPA010917 anti-TREM2 antibody, suggest that TREM2 is not expressed by microglia but instead seems to be a marker of recruited monocytes in the human brain. This finding has implications with regards to the role of TREM2 as a risk factor, emphasizing the importance of systemic immune responses in the development and progression of Alzheimer's disease. PMID- 28987035 TI - The Psychoneuroimmunological Role of Omega-3 Polyunsaturated Fatty Acids in Major Depressive Disorder and Bipolar Disorder. AB - Context * Psychoneuroimmunology is the interdisciplinary study that links behavioral health with the neuroendocrinal system and investigates that link's bidirectional impact on the human immune system. Mechanistic studies have shown how omega-3 polyunsaturated fatty acids (PUFAs), like those found in fish oil, can modulate key pathways involved in inflammation, sympathetic activity, oxidative stress, transcription factors, and inflammatory cytokine production. Objective * The research team intended to investigate the effects that PUFAs have on the brain and the immune system, including the effects of proinflammatory cytokines and oxidative stress, and their therapeutic benefits in major depressive disorder (MDD) and bipolar disorder, either as an alternative monotherapy or a complementary adjunct treatment. Design * A literature search was conducted through PubMed and Google Scholar, with no restrictions on the publication dates or geographically. Setting * The research occurred at research facilities in Washington, DC, and Davis, California. Results * Well-described links between inflammation and MDD and bipolar disorder have been established. Similarly, a highly inflammatory state is a contributing factor to many significant health complications, and omega-3 PUFAs can help treat those issues. Conclusions * The research team concluded that omega-3 fatty acids have therapeutic benefits in the treatment of both MDD and bipolar disorder and are effective as a monotherapy and, particularly, as an adjunct therapy. The efficacy of omega-3 supplementation is clearly useful in promoting better health overall and supplementation should be encouraged in the primary care setting. A meta analysis exploring an adjunct treatment of supplemental eicosapentaenoic acid or docosahexaenoic acid is likely to yield the greatest benefits to psychiatric conditions and provide an answer to proper dosing regimens. The team also created a chart of the supplements' salient features, demonstrating the overall health benefits of omega-3 fatty acids. PMID- 28987034 TI - Impact of patient characteristics and treatment procedures on hospitalization cost and length of stay in Japanese patients with influenza: A structural equation modelling approach. AB - OBJECTIVES: Little is known about the economic burden of influenza-related hospitalizations in Japan. This study sought to identify the factors that contribute to the total healthcare costs (THCs) associated with hospitalizations due to influenza in the Japanese population. STUDY DESIGN: A retrospective cross sectional database analysis study. METHODS: A structural equation modelling approach was used to analyse a nationwide Japanese hospital claims data. This study included inpatients with at least 1 confirmed diagnosis of influenza and with a hospital stay of at least 2 days, who were admitted between April 2014 and March 2015. RESULTS: A total of 5261 Japanese inpatients with a diagnosis of influenza were included in the final analysis. The elderly (>=65 years) and the young (<=15 years) comprised more than 85% of patients. The average length of stay (LOS) was 12.5 days, and the mean THC was 5402 US dollars (US$) per hospitalization. One additional hospital day increased the THC by 314 US$. Intensive care unit hospitalizations were linked to higher costs (+4957 US$) compared to regular hospitalizations. The biggest procedure-related cost drivers, which were also impacted by LOS, were blood transfusions (+6477 US$), tube feedings (+3501 US$) and dialysis (+2992 US$). CONCLUSIONS: In Japan, the economic burden due to influenza-related hospitalizations for both children and the elderly is considerable and is further impacted by associated comorbidities, diagnostic tests and procedures that prolong the LOS. PMID- 28987036 TI - Prayer Healing: A Case Study Research Protocol. AB - Context * Prayer healing is a common practice in many religious communities around the world. Even in the highly secularized Dutch society, cases of prayer healing are occasionally reported in the media, often generating public attention. There is an ongoing debate regarding whether such miraculous cures do actually occur and how to interpret them. Objective * The aim of the article was to present a research protocol for the investigation of reported cases of remarkable and/or unexplained healing after prayer. Design * The research team developed a method to perform a retrospective, case-based study of prayer healing. Reported prayer healings can be investigated systematically in accordance with a step-by-step methodology. The focus is on understanding the healing by studying it from multiple perspectives, using both medical judgment and patients' narratives collected by qualitative methods Setting * The study occurred at Vrije Universiteit (VU) and VU Medical Center (Amsterdam, Netherlands) as well as the general medical practice of the first author. Participants * Potential participants could be any individuals in the Netherlands or neighboring countries who claim to have been healed through prayer. The reports of healing came from multiple sources, including the research team's medical practices and their direct vicinities, newspaper articles, prayer healers, and medical colleagues. Outcome Measures * Medical data were obtained before and after prayer. Subsequently, a member of a research team and of a medical assessment committee made a standardized judgment that evaluated whether a cure was clinically remarkable or scientifically unexplained. The participants' experiences and insider perspectives were studied, using in-depth interviews in accordance with a qualitative research methodology, to gain insight into the perceptions and explanations of the cures that were offered by participants and by the members of the medical assessment committee. The medical findings and participants' experiences were weighed and interpreted based on a transdisciplinary framework, including biopsychosocial and theological perspectives, with reference to a conceptual framework derived from Ian Barbour's typology of positions in the science-religion debate. Conclusion * A case-based, research study protocol that compares medical and experiential findings and that interprets and structures those findings with reference to Ian Barbour's conceptual model is an innovative way of gaining deeper insight into the nature of remarkable and/or unexplained cures. PMID- 28987037 TI - Hypnosis and Osteopathic Manipulative Treatment for Visual Disorders During Pregnancy: A Case Report. AB - Context * Pregnancy causes physiological alterations to the visual system, particularly in relation to retinal vascularization, with a consequent increase of intraocular pressure, and to the lacrimal fluid, with a consequent ocular dryness, which both can lead to a reduction in visual acuity. Numerous case reports refer to the employment of hypnotic treatment in cases of myopia, but the literature does not report any case of decreased visual acuity postpartum that was treated with hypnosis. Objective * For women with visual disorders that had appeared during pregnancy or were preexisting, the study intended to evaluate the benefits of treatment of the diaphragm by hypnotherapy and osteopathy to modify intracorporeal pressure and restore the women's visual function. Design * The research team performed a case study. Setting * The setting was a private osteopathic clinic. Participant * The participant was a 35-y-old woman lacking visual acuity postpartum. Intervention * The study took place during a period of 1 d. The participant first took part in a hypnotherapy session, the first intervention, and then participated in an osteopathic session, the second intervention. Outcome Measures * For the first evaluation of visual function at baseline, 3 tests were performed: (1) a visual acuity test; (2) a cover test for near and distance vision; and (3) a test for near point convergence. The visual function evaluation (all 3 tests) occurred after the 2 types of treatment (T1, T2). Finally, a visual function evaluation (all 3 tests) occurred at a follow-up session 1 mo after the end of treatment (T3). Results * The intervention produced a significant improvement in visual acuity, due to the multidisciplinary approach of treatment with hypnotherapy and osteopathy, and achieved a result that was maintained in the medium term. Conclusions * Hypnosis and osteopathy produced a significant improvement in visual acuity and the result was maintained in the medium term. Further studies are needed to verify the efficacy of the 2 treatments. PMID- 28987038 TI - Electric Nutrition: The Surprising Health and Healing Benefits of Biological Grounding (Earthing). AB - Context * Modern biomedicine has discovered that many of the most debilitating diseases, as well as the aging process itself, are caused by or associated with chronic inflammation and oxidative stress. Emerging research has revealed that direct physical contact with the surface of the planet generates a kind of electric nutrition, with surprisingly potent and rapid anti-inflammatory and antioxidant effects. Objectives * The objective of this study was to explain the potential of grounding to clinicians as a simple strategy for prevention, therapy, and improving patient outcomes. The research summarized here has pursued the goal of determining the physiological and clinical significance of biological grounding. Design * The research team has summarized more than 12 peer-reviewed reports. Where appropriate, blinded studies examined in this paper were conducted using a variety of statistical procedures. Interventions * In all cases, the intervention examined conductive contact between the surface of Earth and the study's participants, using conductive bed sheets, floor or desk pads, and electrode patches, such as those used in electrocardiography. Results * All studies discussed revealed significant physiological or clinical outcomes as a result of grounding. Conclusion * This body of research has demonstrated the potential of grounding to be a simple, natural, and accessible clinical strategy against the global epidemic of noncommunicable, degenerative, inflammatory related diseases. PMID- 28987039 TI - Reduction in Pain After Use of Bioceramic Undershirt for Patients With Fibromyalgia. AB - Context * The treatment of pain in fibromyalgia (FM) has centered on pharmacotherapy and nonpharmacological treatment. The nondrug treatments for FM include the effects of far infrared radiation (FIR). Currently, FIR-emitting heat lamps and garments made of filaments (fibers) impregnated with FIR-emitting nanoparticles are being used to deliver thermal radiation effects. Objective * The study intended to determine the benefits of a fabric coated with bioceramics for reducing pain in women with FM. Design * The research team designed a randomized, controlled pilot study. Setting * The study was conducted in the laboratory of the Department of Corporal Expression, University of Jaen (Jaen, Spain). Participants * Thirty-nine female participants diagnosed with FM took part in the study. Intervention * Participants were randomly assigned to an experimental (intervention) group (EG), n = 20, or a placebo group (PG), n = 19. The EG wore a shirt impregnated with bioceramics, and the PG dressed in a shirt without bioceramics. Both groups wore the shirts for 8 h/d for 60 d. Outcome Measures * Participants were evaluated twice, at baseline and postintervention. The tests used were (1) a visual analogue scale (VAS) for pain, (2) the FM Impact Questionnaire (FIQ), and (3) the Short Form-12 health survey. The research team measured each participant's weight, height, and body mass index and evaluated their tender points. The research team also tracked participants' daily use of pain medications as a daily tablet intake. Results * Postintervention, the women in the EG showed a significant reduction in pain: (1) on the VAS (P < .001), (2) on the measurement of tender points (P < .001), and (3) on the algometer score (P < .001), as well as (4) a significant reduction in FM symptoms on the FIQ (P = .005) and (5) a reduction in daily tablet intake (P < .001). No significant changes in the PG group were found. Significant differences existed between the groups for the VAS, the FIQ, tender points, and the algometer score in posttest evaluation (P < .05). Conclusions * Regular use of garments impregnated with a bioceramic solution (1%) can be beneficial in reducing pain and the impact of FM for patients. The low cost and comfort of the clothing make the therapy easy to be applied as a complementary tool in the treatment of FM. PMID- 28987040 TI - [History of the study, epidemiology of the disease and characterization of Borrelia burgdorferi infection]. AB - From the beginning of the twentieth century interest in tick-borne borreliosis continues to be an important diagnostic and therapeutic problem. In 1977, in Lyme and Old Lyme, Cunnecticut, in the United States, arthritis and skin lesions were described in 12 children, which were associated with tick bites. The name of the place was called a syndrome of Lyme disease. Dr Willy Burgdorfer observed microaerophilic Gram-negative bacteria (Spirochetes) with a diameter of 0.3-0.5 um and a length of about 20-30 um, which were isolated from the tick colon. Lyme disease (borreliosis) is the most common tick-borne disease in the world. In Poland, most cases of Lyme disease occur between May and November, and more than 80% of cases are found in June and July during the nymph ticks feeding. The northern part of the country is considered endemic. The reservoir of bacteria is about 300 different species of mammals. These are mainly rodents of the norovirus and mouse family, and live deer, deer and wolves, as well as some species of birds. Ticks are infected with Borelia burgdorferi through the blood of infected animals. However, adult ticks are infested with Lyme spirochetes, depending on the region of the country. It infects 5-20% nymph and 15-40% adult individuals. The sequence of the Lyme disease spirochetes reveals a number of interesting traits. Classical virulence factors have not been isolated and therefore it is suspected that the vertebrate does not contain it in relation to mammals. However, a number of lipoproteins have been defined and some of them may be factors contributing to the innate immune system. PMID- 28987041 TI - [Treatment of ischemic stroke with mechanical trombectomy systems]. AB - : The implementation of ischemic stroke therapy has created new opportunities for clinical improvement and the reversal of adverse prognosis in patients with ischemic stroke. Mechanical thrombectomy has become the recommended treatment for acute stroke in a select group of patients and in highly specialized centres with experience in endovascular therapy. AIM: The aim of the study was to evaluate of the efficacy and safety of mechanical thrombectomy in patients with acute ischemic stroke within the first six hours of illness was reported. MATERIALS AND METHODS: 34 patients previously hospitalized in the Department of Neurology due to ischemic stroke were included in the study during the first six hours of illness. Short-term efficacy and safety (1 month after surgery) and long-term (3 months) were evaluated based on the assessment of early mortality, functional status and neurological status. Factors that increase the risk of death were also analyzed. RESULTS: In the study group, the recanalization of the vessel was obtained in 52% of patients, which was associated with a significant improvement of functional status. Improvements in functional and neurological status were obtained in most of the patients (63%), including very good functional status (mRS 0-1) in 7 (20%) patients upon discharge from the hospital. CONCLUSIONS: In the study group, the recanalization of the vessel was obtained in 52% of patients, which was associated with a significant improvement of functional status. Improvements in functional and neurological status were obtained in most of the patients (63%), including very good functional status (mRS 0-1) in 7 (20%) patients upon discharge from the hospital. PMID- 28987042 TI - [Obesity, overweight as main risk factors of cancer in Sanok's county population]. AB - : Weight disorder such as obesity and overweight are an significant risk factor in cancer development. AIM: The aim of the study was to determine an obesity and overweight in cancer prevention among the population of Sanok's county. MATERIALS AND METHODS: The research was conducted in 157 residents of Sanok's county in 2015 yrs. A method of diagnostic survey and conventional survey was used. The main research tool was a selfmade survey. In the evaluation of statistical significance we have accepted the level of p<0,05. RESULTS: Almost half of the respondents of the survey declared doing sport regularly and most of them were young people with higher education. Almost half of the responders had good BMI, one third was overweight and one tenth was obese. The latter weight disorder was mostly common among men and people with vocational and primary education. CONCLUSIONS: Risk factor of cancer in the study group were: overweight, obesity and low level of physical activity. Age, sex and place of residence conditioned the level of physical activity and up keeping proper body weight. These studies require constant increase of awareness in the area of physical activity and maintaining proper body weight. PMID- 28987043 TI - [Low level of physical activity as main risk factor of cancer in Sanok's county population]. AB - : Physical activity is a key component of a healthy lifestyle. The data of WHO conclude that little physical activity is the fourth key risk factor of premature death. Weight disorder such as obesity and overweight are an significant risk factor in cancer development. AIM: The aim of the study was to determine physical activity in cancer prevention among the population of Sanok's county. MATERIALS AND METHODS: The study covered a group 157 residents of Sanok's county in 2015. A method of diagnostic survey and conventional survey was used. The main research tool was a selfmade survey. The p values p<0.05 were considered statistically significant. RESULTS: Almost half of the respondents of the survey declared doing sport regularly and most of them were young people with higher education. The preferred form of physical activity among the survey group was jogging. Only one third of surveyed people declared regular physical activity. The responders usually evaluated their level of physical activity as medium. The main reasons for physical activity were: achieving better wellbeing and maintaining good physical condition, whereas laziness and lack of time were the main reasons of the lack of physical activity. Responders most often spend from 30-90 minutes on working out on their workout days. CONCLUSIONS: Risk factor of cancer in the study group were physical activity. Age, sex and place of residence conditioned the level of physical activity and up keeping proper body weight. These studies require constant increase of awareness in the area of physical activity. PMID- 28987044 TI - [Application of Brain-Boy Universal Professional in preliminary assessment of auditory processing disorder]. AB - : Increasing numbers of hearing pathology is auditory processing disorders. Auditory Processing Disorders (APD) are defined as difficulty in using auditory information to communicate and learn in the presence of normal peripheral hearing. It may be recognized as a problem with understanding of speech in noise and perception disorder of distorted speech. APD may accompany to articulation disorders, language problems and difficulties in reading and writing. The diagnosis of auditory processing disorders causes many difficulties primarily due to the lack of common testing procedures, precise criteria for qualification to the group of norm and pathology. The Brain-Boy Universal Professional (BUP) is one of diagnostics tools. It enables to assess the higher auditory functions. AIM: The aim of the study was preliminary assessment of hearing difficulties that may suggest the occurrence of auditory processing disorders in children. The questionnaire of hearing difficulties and BUP was used. MATERIALS AND METHODS: Study includes 20 participants 2nd grade students of elementary school. The examination of the basic central functions was carried out with BUP. The parents and teacher complete the questionnaire to evaluate the hearing problems. RESULTS: Studies carried out indicate that the 40% schoolchild have hearing difficulties. The high percentage of deficits in auditory functions was confirmed with research results of medical device and the questionnaire for teacher. CONCLUSIONS: On the basis of the studies conducted may establish that the Warnke Method can serve as preliminary assessment of hearing difficulties that may suggest the occurrence of auditory processing disorders in children. PMID- 28987045 TI - Acalculous cholecystitis in a female with cardiac device-related infective endocarditis. AB - Acute acalculous cholecystitis (AAC) is a necroinflammatory disease of the gallbladder with no gallstones present. ACC is known to be a serious, even potentially lethal complication observed mainly in patients with various severe underlying conditions including trauma, burn and sepsis. Infection of cardiac implantable electronic devices may lead to cardiac device-related infective endocarditis (CDRIE). The authors describe a case of a 55-year-old female with a history of advanced heart failure and implantation/reimplantation of biventricular pacemaker/defibrillator (CRT-D) for cardiac resynchronization therapy. She was admitted presently due to the symptoms of septicemia. Echocardiography revealed CDRIE with mobile vegetations on pacemaker leads; chest computed tomography showed pulmonary infarctions. Staphylococcus aureus was cultured from the blood. Antibiotics were applied in accordance with antimicrobial susceptibility and were continued after percutaneous leads extraction and pacemaker explantation. After 6 weeks of hospitalization, nonspecific abdominal symptoms developed, ultrasonography and computed tomography confirmed AAC diagnosis. Laparoscopic cholecystectomy was performed. To the best of the authors' knowledge, the case presented is the first report of ACC in a patient with CDRIE due to infection of pacemaker leads. PMID- 28987046 TI - [IgG4-related disease - a case report]. AB - : Immunoglobulin G4-related disease (IgG4-RD) is a comparatively new condition that may involve more than one organ. The lack of characteristic, pathognomonic clinical symptoms may delay the diagnosis of this disease. The diagnosis is based upon clinical manifestation, elevated serum levels of IgG4 and histopathologic examination with immunohistochemical staining to reveal infiltration of IgG4 positive plasma cells. The first line treatment is oral glucocorticoids. A CASE REPORT: 38-year-old woman with Hashimoto disease, chronic sinusitis and chronic hepatitis of unknown etiology was admitted to the Department of Endocrinology because of moderate eyelids swelling accompanied by redness for 3 years. Graves' orbitopathy and systemic vasculitis were suspected, however both were excluded (negative antibodies results: anty-TSHR, ANCA, ANA). Serologic investigation of Sjogren's syndrome was also negative. In Magnetic Resonance Imaging (MRI) of orbits there were described bilateral mild extension of lateral rectus muscles, normal signal of adipose tissue and bilateral lacrimal glands enlargement. Moreover, increased IgG4 serum levels were detected. The material derived from perinasal sinuses surgery was analyzed in histopathology examination with immunohistochemical staining, which revealed characteristic features of chronic inflammatory process and increased numbers of IgG4 - positive plasma cells (>50 in a large field of view). The diagnosis of IgG4-RD was established. Because of non-effective oral methylprednisolone therapy in the past, the patient was referred to Clinic of Rheumatology for further treatment. After the therapy with methylprednisolone and azathioprine there were observed the significant reduction of symptoms. CONCLUSIONS: Because of lack of characteristic symptoms of IgG4- RD, it should be always considered in differential diagnosis of chronic inflammatory diseases of various organs. PMID- 28987047 TI - [Epidemiology and risk factors of hepatocellular carcinoma]. AB - Primary liver neoplasms occurs relatively rarely in Poland. The most frequently occurring type of cancer is hepatocellular carcinoma (HCC), which globally constitutes 7% of all the occurrences of cancer. The incidence increases with age and is the highest in patients around the age of 70. It also varies significantly depending on the geographic location. The main factors that cause HCC are infection of HBV and HCV, whose genome integrates into the DNA of the host, causing mutations. The other factors include excessive alcohol consumption, contact or consumption of Aspergillus toxins as well as various metabolic disorders, such as alpha1-antitrypsin deficiency, hemochromatosis, tyrosinemia, porphyria, von Gierke disease and in person with gene mutation p.I148M of adiponutrin. HCC is usually detected incidentally, during ultrasound examination or during clinical diagnosis of liver failure. HCC can be diagnosed using computed tomography (CT) or magnetic resonance imaging (MRI), which is considered the most accurate diagnostic method. A core needle biopsy or the examination of the level of markers such as: alpha-fetoprotein (AFP), D-gamma-carboxy prothrombin (DCP), tumourassociated glycoprotein 72 (CA 72-4, TAG-72), are advised for a complete diagnostics. PMID- 28987048 TI - [The application of N-acetylcysteine in optimization of specific pharmacological therapies]. AB - Based on the analysis of data from clinical trials it could be postulated that N acetylcysteine has a positive impact on the treatment of various diseases. However, less is known about specific molecular and physiological mechanisms underlying the reported therapeutic effects. N-acetylcysteine (NAC, N-acetyl-L cysteine) is an amino acid derivative containing a thiol group. It is a precursor of L-cysteine and glutathione. NAC is well absorbed and safe for the body at doses up to 300 mg per kg of body weight. Side effects are relatively rare. NAC is used as an mucolytic agent in adjunctive therapy of respiratory diseases causing the retention of secretions, as well as an antidote in the treatment of paracetamol poisoning. Moreover, NAC protects against the toxic effects of reactive oxygen species and their active metabolites. NAC is involved in free radical scavenging processes via several independent mechanisms, including a direct reduction of free radicals, providing substrates for oxidation-reduction reactions and activation of antioxidant enzymes. In the blood, NAC decreases the level of low density lipoprotein peroxidation. In various tissues, NAC may increase the levels of glutathione and cysteine and stimulate the superoxide dismutase action. NAC is used as a supplement in the treatment of various diseases associated with impaired exterior and intracellular oxidative balance. NAC increases the concentrations of amino acids and their derivatives, including cysteine, cystine, and glutathione. It also stabilizes the antioxidant status of the cells and the intercellular spaces. NAC changes the levels of transcription factors, modifying the transcription of selected genes and acting on the protein translation. It works on the activation of several enzymes in the cells and outside the cells. Based on the analysis of data from clinical trials it can be concluded, that an administration of NAC may be beneficial for these groups of patients, in whom the reversible accumulation and the negative action of free radicals was observed. PMID- 28987049 TI - Downregulation of Cohesin Loading Factor Nipped-B-Like Protein (NIPBL) Induces Cell Cycle Arrest, Apoptosis, and Autophagy of Breast Cancer Cell Lines. AB - BACKGROUND The cohesin loading factor, nipped-B-like protein (NIPBL), is also known as the sister chromatid cohesion 2 (SCC2) human homolog. Recently, we have studied the role of expression levels of NIPBL in cell proliferation and chemotherapy resistance of non-small cell lung cancer (NSCLC) cells in vitro. The aim of this study was to investigate the effects of expression of the cohesin loading factor, NIPBL, on the cell cycle, apoptosis, and autophagy of breast cancer cell lines in vitro. MATERIAL AND METHODS Expression levels of the NIPBL in the breast cancer cell lines, MCF7, Bcap37, MDA-MB 453 and MDA-MB 231, were measured using Western blot and flow cytometry. Small interfering RNA (si-RNA) was used to study the biological functions of NIPBL. The cell counting kit-8 (CCK 8) assay and the colony formation assay were used to measure cell proliferation; the wound scratching assay and transwell chamber assay were used to investigate cell invasion and migration. RESULTS NIPBL gene and protein expression were upregulated in the MCF7 and Bcap37 cells; si-NIPBL transfection inhibited cell proliferation, invasion, and migration of breast cancer cells. Downregulation of NIPBL arrested cells in the G0/G1 phase of the cell cycle and induced apoptosis and autophagy of breast cancer cells through the caspase3 and mammalian target of rapamycin (mTOR) signaling pathways. CONCLUSIONS [color=black]Downregulation of cohesin loading factor NIPBL arrested breast cancer cells in vitro in the G0/G1 phase of the cell cycle and induced apoptosis and autophagy. [/color]. PMID- 28987050 TI - Editorial. AB - no summary. PMID- 28987051 TI - Financing of forensic psychiatry in view of treatment quality and threat to public safety. AB - Stay in a psychiatric hospital of persons who committed the gravest criminal acts while in a state of insanity aims to ensure their effective treatment (therapeutic function), but above all to prevent the repetition of prohibited acts of significant harm to the community (preventive function). Forensic patients are provided with suitable medical, psychiatric, rehabilitation and resocialization care. The court imposes an indefinite detention. In view of the dual purpose of the stay in a psychiatric hospital, both therapeutic and preventive, the treatment costs generated by forensic wards are higher than those of general psychiatric wards. This prompts person from outside psychiatry, who do not understand the nature of preventive measures, to call for continuing reductions in the expenditure on forensic psychiatric care. It is, therefore, worth analyzing the possible meaning and results of the attempts to economizeforensic psychiatry, to find savings and to manipulate financing system under the pretence of economic incentive to improve treatment quality. In this paper, the authors address and discuss the above and other issues. PMID- 28987052 TI - Recovered memories in clinical practice - a research review. AB - The problem of recovered memories concerns not only psychiatry, psychology or psychotherapy but it is also an important legal and judicial issue. Clinicians, scientists and lawyers are in unsolved dispute, called "memory wars", concerning the credibility of these memories, especially if they were recovered following specific therapeutic techniques or using self-help books. Many cases of recovered memories of childhood sexual abuse brought legal action against alleged offender. Investigations showed, however, that some of these memories were false. The aim of this article is to try to answer key questions concerning the issue if recovered memories: Is it possible not to remember traumatic experiences? In what conditions the autobiographical memories can be implanted? Is it possible to make a list of therapeutic techniques evoking false memories? What are the characteristics of a patient particularly vulnerable for false memories creation? Answers to the above questions are a ground for considerations concerning creation of favorable conditions for therapeutic work and minimizing mistakes resulting from the risk of implanting false memories. PMID- 28987053 TI - Characteristics and experience of the patient in psychotherapy and the psychotherapy's effectiveness. A structural approach. AB - OBJECTIVES: The study concerns the relationship between three groups of variables presenting the patient's perspective: (1) "patient's characteristics" before psychotherapy, including "expectations of the therapy"; (2) "experience in the therapy", including the "psychotherapeutic relationship"; and (3) "assessment of the direct effectiveness of the psychotherapy". Data from the literature are the basis for predicting relationships between all of these variables. METHODS: Measurement of the variables was conducted using a follow-up survey. The survey was sent to a total of 1,210 former patients of the Academic Center for Psychotherapy (AOP) in which the therapy is conducted mainly with the students and employees of the University of Warsaw. Responses were received from 276 people. 55% of the respondents were women and 45% were men, under 30 years of age. The analyses were performed using structural equations. RESULTS: Two models emerged from an analysis of the relationship between the three above-mentioned groups of variables. One concerns the relationship between (1) the patient's characteristics (2) the course of psychotherapy, in which -from the perspective of the patient - there is a good relationship with the psychotherapist and (3) psychotherapy is effective. The second model refers to (2) the patient's experience of poor psychotherapeutic relationship and (3) ineffective psychotherapy. CONCLUSIONS: Patient's expectations of the psychotherapy (especially "the expectation of support") proved to be important moderating variablesin the models-among the characteristics of the patient. The mathematical model also revealed strong correlation of variables measuring "the relationship with the psychotherapist" and "therapeutic interventions". PMID- 28987054 TI - The effects of short-term group psychodynamic psychotherapy on the personality traits of patients treated in a day ward. AB - OBJECTIVES: In the literature, there is no research that would indicate how a change in specific personality elements may affect the therapeutic effect of short-term group psychodynamic psychotherapy (STGP). The aim of the study was to evaluate the effect of short-term group psychodynamic psychotherapy on personality traits in apopulation of patients with neurotic and personality disorders in a day ward of neurosis treatment. METHODS: The study involved 139 people with anxiety and personality disorders, including 110 who participated in the control measurements. The dimensions of personality (neuroticism, extraversion, psychoticism, lie) were assessed on the basis of the Eysenck Personality Questionnaire (EPQ) adapted to the Polish conditions. The measurements were made at two time points: (1) before treatment, (2) after 12 weeks of treatment. RESULTS: During therapy the level of neuroticism, extraversion, psychoticism and lie did not change significantly in the group of neurotic patients. In the group of people with personality disorders, the level of neuroticism significantly decreased (p = 0.0008), whereas the level of extraversion increased (p = 0.037). The values for psychoticism and lie did not change significantly in the course of psychotherapy in any group of patients. CONCLUSIONS: The dynamics of changes in neuroticism and extraversion under the influence of short-term group psychodynamic psychotherapy (STGP) in a day ward of neurosis treatment seems to be an important marker for assessing the effectiveness of the treatment in people suffering from personality disorders. There is a need to develop more precise parameters for the assessment of recovery in the group of people with anxiety disorders. PMID- 28987055 TI - The pattern of verbal, visuospatial and procedural learning in Richardson variant of progressive supranuclear palsy in comparison to Parkinson's disease. AB - OBJECTIVES: Progressive supranuclear palsy (PSP) is regarded either within spectrum of atypical parkinsonian syndromes or frontotemporal lobar degeneration. We compared the verbal, visuospatial and procedural learning profiles in patients with PSP and Parkinson's disease (PD). Furthermore, the relationship between executive factors (initiation and inhibition) and learning outcomes was analyzed. METHODS: Thirty-three patients with the clinical diagnosis of PSP-Richardson's syndrome (PSP-RS), 39 patients with PD and 29 age -and education -matched controls were administered Mini-Mental State Examination (MMSE), phonemic and semantic fluency tasks, Auditory Verbal Learning Test (AVLT), Visual Learning and Memory Test for Neuropsychological Assessment by Lamberti and Weidlich (Diagnosticum fur Cerebralschadigung, DCS), Tower of Toronto (ToT) and two motor sequencing tasks. Patients with PSP-RS and PD were matched in terms of MMSE scores and mood. RESULTS: Performance on DCS was lower in PSP-RS than in PD. AVLT delayed recall was better in PSP-RS than PD. Motor sequencing task did not differentiate between patients. Scores on AVLT correlated positively with phonemic fluency scores in both PSP-RS and PD. ToT rule violation scores were negatively associated with DCS performance in PSP-RS and PD as well as with AVLT performance in PD. CONCLUSIONS: Global memory performance is relatively similar in PSP-RS and PD. Executive factors (initiation and inhibition) are closely related to memory performance in PSP-RS and PD. Visuospatial learning impairment in PSP-RS is possibly linked to impulsivity and failure to inhibit automatic responses. PMID- 28987056 TI - The role of the cerebellum in the regulation of language functions. AB - The present paper is a review of studies on the role of the cerebellum in the regulation of language functions. This brain structure until recently associated chiefly with motor skills, visual-motor coordination and balance, proves to be significant also for cognitive functioning. With regard to language functions, studies show that the cerebellum determines verbal fluency (both semantic and formal) expressive and receptive grammar processing, the ability to identify and correct language mistakes, and writing skills. Cerebellar damage is a possible cause of aphasia or the cerebellar mutism syndrome (CMS). Decreased cerebellocortical connectivity as well as anomalies in the structure of the cerebellum are emphasized in numerous developmental dyslexia theories. The cerebellum is characterized by linguistic lateralization. From the neuroanatomical perspective, its right hemisphere and dentate nucleus, having multiple cerebellocortical connections with the cerebral cortical language areas, are particularly important for language functions. Usually, language deficits developed as a result of a cerebellar damage have subclinical intensity and require applying sensitive neuropsychological diagnostic tools designed to assess higher verbal functions. PMID- 28987057 TI - Polish Adult Reading Test (PART) - construction of Polish test for estimating the level of premorbid intelligence in schizophrenia. AB - OBJECTIVES: In view of unavailability in Poland of the standardized methods to measure PIQ, the aim of the work was to develop a Polish test to assess the premorbid level of intelligence - PART(Polish AdultReading Test) and to measureits psychometric properties, such as validity, reliability as well as standardization in the group of schizophrenia patients. METHODS: The principles of PART construction were based on the idea of popular worldwide National Adult Reading Test by Hazel Nelson. The research comprised a group of 122 subjects (65 schizophrenia patients and 57 healthy people), aged 18-60 years, matched for age and gender. RESULTS: PART appears to be a method with high internal consistency and reliability measured by test-retest, inter-rater reliability, and the method with acceptable diagnostic and prognostic validity. The standardized procedures of PART have been investigated and described. CONCLUSIONS: Considering the psychometric values of PART and a short time of its performance, the test may be a useful diagnostic instrument in the assessment of premorbid level of intelligence in a group of schizophrenic patients. PMID- 28987058 TI - Verbal fluency in research conducted with PET technique under conditions of extended cognitive activation with the use of 18F-fluorodeoxyglucose (FDG) tracer. AB - OBJECTIVES: Functional neuroimaging of the brain is a widely used method to study cognitive functions. The aim of this study was to compare the activity of the brain during performance of the tasks of phonemic and semantic fluency with the paced-overt technique in terms of prolonged activation of the brain. METHODS: The study included 17 patients aged 20-40 years who were treated in the past for Hodgkin'slymphoma, now in remission. Due to the type of task, the subjectswere divided into two groups. Nine people performed the phonemic fluency task, and eight semantic. Due to the disease, all subjects were subject to neuropsychological diagnosis. The diagnosis of any cognitive impairment was an exclusion criterion. Neuroimaging was performed using PET technique with 18F fluorodeoxyglucose (FDG) tracer. RESULTS: Performance of a verbal fluency test, regardless of the version of the task, was associated with greater activity of the left hemisphere of the brain. The most involved areas compared with other areas of key importance for the performance of verbal fluency tasks were frontal lobes. An increased activity of parietal structures was also shown. CONCLUSIONS: The study did not reveal differences in brain activity depending on the type of task. Performing the test in both phonemic and semantic form for a long time, in terms of increased cognitive control resulting from the test procedure, could result in significant advantage of prefrontal lobe activityin both types of tasks and made it impossible to observe the processes specific to each of them. PMID- 28987059 TI - Executive dysfunction in late-life depression. AB - OBJECTIVES: Nowadays there are numerous reports stressing the occurrence of cognitive functions disorders in late-life depression (LLD). More and more frequently the studies stress the role of executive dysfunctions in LLD. The purpose of the study was an evaluation of the components of executive functions in non-demented LLD patients, as well as an evaluation of the relation between the individual components of executive functions and the level of depressiveness. METHODS: The study included 87 persons with depression and 100 persons in the control group. For the purpose of a screening evaluation of cognitive functions the Mini-MentalState Examination (MMSE) was applied. For the evaluation of the level of executive functions efficiency the following were chosen: a) Trail Making Test (TMT), b) Verbal Fluency Tests (VFT) and c) go/no-go task (GNG). RESULTS: A significant difference was found in the levels of efficiency of all the components of executive functions in patients with late-life depression. The patients with depression demonstrated the slowest psychomotor speed and worse results in the tests evaluating cognitive flexibility, semantic fluency and inhibition. Statistically significant relation was observed between the higher result in GDS-SF (Geriatric Depression Scale-Short Form) and the worse performance in the GNG test. CONCLUSIONS: The patients with depression demonstrated a significant impairment of executive functions. A relation was found between the cognitive control disorder and the level of depressiveness. Executive dysfunctions can play an important role in the persistence of depressive symptoms. Identification of patients with depression and executive dysfunctions has significant therapeutic implications. PMID- 28987060 TI - Psychometric properties of the Polish adaptation of short form of the Empathy Quotient (EQ-Short). AB - OBJECTIVES: The purpose of the present study was to analyze the psychometric properties of the Polish-language version of the EQ-Short questionnaire, designed to measure affective and cognitive empathy. METHODS: 940 subjects, aged 15-80, took part in the study. Subjects fluent in both Polish and English (N = 31) completed the questionnaire in the original English version and its Polish translation. The remaining subjects (N = 909) participated in a study designed to verify construct validity and reliability of the Polish version of the tool. RESULTS: The Polish and English versions of the EQ-Short show linguistic equivalence at a satisfactory level (r = 0.80, p < 0.001). Tests of validity and reliability of the translated tool showed that the Polish-language EQ-Short has good psychometric properties (Cronbach's alpha = 0.78), comparable to the original version. In all age groups there were statistically significant sex differences in EQ-Short scores: women scored higher than men. CONCLUSIONS: The Polish-language adaptation of EQ-Short is linguistically and psychometrically similar to the English original and meets the criteria of a reliable tool for measuring empathy. PMID- 28987061 TI - Evaluation of white matter structure changes, as assessed in tractography, and cognitive dysfunctions in patients with early onset schizophrenia and their first degree relatives. AB - OBJECTIVES: The aim of the project was to assess the differences in the white matter (WM) fiber structure between patients with early onset schizophrenia (EOS), their first degree relatives and controls using Fractional Anisotropy (FA), and an independent evaluation of the severity of working memory disturbances in the study groups. METHODS: The study included 20 patients diagnosed with paranoid EOS (diagnosed before the age of 18), a group of 20 parents of patients, matched for gender, and 18 healthy controls. All study participants were examined with Diffusion Tensor Imaging (DTI,1.5 T) and selected neuropsychological tests to assess working memory, immediate memory and attention (Trail Making Test parts A and B: TMT-A and TMT-B, Digit Span Forward and Backward). RESULTS: No significant differences in FA parameters were found between the analyzed groups. The group of patients took significantly longer to perform the TMT-A and TMT-B than the control group, and achieved worse outcomes in Digit Span tests. The relatives of the patients achieved lower scores in Digit Span tests and needed more time to perform TMT-B compared to controls. There were no significant differences between all groups in terms of the number of errors when performing TMT-A and TMT-B. CONCLUSIONS: The results of our study indicate a reduction in the capacity of immediate memory, working memory, cognitive plasticity and divided attention, both in EOS patients and their first degree relatives compared to healthy subjects. The reported neuropsychological deficits were not reflected in WM integrity, as assessed with FA. PMID- 28987062 TI - Aggressiveness and the intensity of psychopathic symptoms - gender differences. AB - OBJECTIVES: The analysis of the recent international reports in the literature on psychopathy has proved irrefutablythat there is a necessity for the in-depth studies on psychopathy among the female sentenced offenders. Although there is no disagreement among the researchers on the 'male' form of this disorder, there are still very few gender comparative studies. The aim of this project was to investigate the relationship between the intensity of particular psychopathic features and aggressive tendencies in a group of female and male inmates. METHODS: 100 incarcerated adult males and 100 incarcerated adult females were studied. To assess the intensity of the psychopathic features the Hare Psychopathy Checklist-Revised (PCL-R; Hare, 2003) was used. Aggressive tendencies were measured using the self-reported Buss-Perry Aggression Questionnaire (AQ; Buss and Perry, 1992). RESULTS: The analysis of variance showed that 12 out of the 20 PCL-R items differentiate indicators of aggressiveness at statistically significant level in the group of male and female prisoners. CONCLUSIONS: The obtained data suggest that there are gender differencesin the manifestation of psychopathy-characteristic features. In both gender groups psychopathic deficiencies can be linked with aggressive behaviors. PMID- 28987063 TI - Dr Jekels' health resort in Bystra near Bielsko: the first treatment centre which adopted psychoanalysis in Poland. AB - The paper sets out to present the history of a health resort and hydrotherapy centre in Bystra near Bielsko from 1898 to 1912. At that time Dr Ludwik Jekels, one of the Polish psychoanalysis forerunners, was the owner of the centre. Initially, Dr Jekels was very enthusiastic about climatic treatment and hydrotherapy, until 1905 when he got interested in psychoanalysis. Shortly afterwards he became its staunch supporter and adopted it as a curative procedure in his health resort. That was the first documented case of psychoanalysis use in Poland. This paper presents the development of the therapeutic centre in Bystra and the characteristic of typical patients receiving treatment there. It also briefly reports on medical histories of the conditions of patients who received psychoanalytic treatment. The paper also focuses on another significant area of Dr Jekels'contact with Sigmund Freud ranging from an accidental meeting in Vienna around 1898, through the summer of 1910 when Jekels looked after Freud's daughters in his spa, to 1912 which saw Jekels'receiving psychoanalytic treatment from Freud. It also presents a detailed analysis of hypotheses why Jekels decided to sell the health resort and move to Vienna. Finally, the significance of Jekels'currently underrated therapeutic work for the development of the Polish psychoanalysis is reiterated. PMID- 28987064 TI - Letter to Editor. Is the nurse able to and should implement some forms of psychotherapy? AB - no summary. PMID- 28987065 TI - Technique-associated outcomes in horses following large colon resection. AB - OBJECTIVE: To compare survival and complications in horses undergoing large colon resection with either sutured end-to-end or stapled functional end-to-end anastomoses. STUDY DESIGN: Retrospective cohort study. ANIMALS: Twenty-six client owned horses with gastrointestinal disease. METHODS: Retrospective data were retrieved from the medical records of 26 horses undergoing colectomy, including 14 horses with sutured end-to-end and 12 horses with stapled functional end-to end anastomoses, between 2003 and 2016. Records were evaluated for signalment, medical and surgical treatments, and survival to hospital discharge. Long-term follow-up was obtained through owner contact. Continuous variables were compared with Mann-Whitney tests. Fisher's exact testing was used to compare survival to hospital discharge. Survival time was compared by constructing Kaplan-Meier survival curves and performing log-rank curve comparison testing. RESULTS: Mean age of horses undergoing colectomy was 13 years. Reason for colectomy was prophylaxis (12) or salvage (14). Mean surgical time was 169 minutes. Mean hospitalization time was 9 days, which did not differ with anastomosis type (P = .62). Nine of 12 horses undergoing stapled functional end-to-end anastomosis and 12 of 14 horses undergoing sutured end-to-end anastomosis survived to hospital discharge (P = .63). Survival time did not differ with anastomosis technique (P = .35). CONCLUSION: Short- and long-term survival outcomes are not different between sutured end-to-end or stapled functional end-to-end anastomoses in horses undergoing colectomy. PMID- 28987066 TI - Co-adsorption of Cations as the Cause of the Apparent pH Dependence of Hydrogen Adsorption on a Stepped Platinum Single-Crystal Electrode. AB - The successful deployment of advanced energy-conversion systems depends critically on our understanding of the fundamental interactions of the key adsorbed intermediates (hydrogen *H and hydroxyl *OH) at electrified metal aqueous electrolyte interfaces. The effect of alkali metal cations (Li+ , Na+ , K+ , Cs+ ) on the non-Nernstian pH shift of the step-related voltammetric peak of the Pt(553) electrode is investigated over a wide pH window (1 to 13) by means of experimental and computational methods. The co-adsorbed alkali cations along the step weaken the OH adsorption at the step sites, causing a positive shift of the potential of the step-related peak on Pt(553). Density functional calculations explain the observations on the identity and concentration of alkali cations on the non-Nernstian pH shift, and demonstrate that cation-hydroxyl co-adsorption causes the apparent pH dependence of "hydrogen" adsorption in the step sites of platinum electrodes. PMID- 28987067 TI - Reconstruction of severe atherosclerotic and obstructive diabetic feet using thoracodorsal artery perforator flaps with long vascular pedicles. AB - BACKGROUND: Foot ulcers in diabetic patients often require free flaps. A long vascular pedicle is mandatory so that more proximal vessels can be used as recipient vessels, especially when the flap is used to reconstruct distal foot defects. We evaluated the outcome of diabetic foot defect that were reconstructed using thoracodorsal artery perforator (TDAP) flaps with long vascular pedicles. PATIENTS AND METHODS: We reconstructed the foot defects of 22 diabetic patients. Nineteen patients were male, and the mean age was 56.4 years. The defects were located in big toe in 11 patients; fourth and/or fifth toe, including lateral aspect of the foot, in 8 patients; and dorsum of the foot, medial plantar, and first metatarsal medial head in 1 patient each. CT angiography showed that the two main vessels of the lower leg remained intact in 7 patients, only one vessel was intact in the lower leg of 11, and no vessels were visible in 4. RESULTS: The flap size ranged between 5 * 4 cm2 and 18 * 11cm2 , with a mean pedicle length of 16.5 cm. The anterior tibial artery was used as the recipient vessel in 15 patients, while the posterior tibial artery was used in 7. All the flaps survived. Three wound disruptions and two partial flap losses healed conservatively, without further surgery. Ulcer due to diabetes recurred in three cases. The mean follow-up period was 46.1 months. All wounds healed completely. CONCLUSIONS: TDAP flaps with long vascular pedicles may be a viable choice for reconstructing defects in the feet of diabetic patients. PMID- 28987068 TI - Associations between methadone maintenance treatment and crime: a 17-year longitudinal cohort study of Canadian provincial offenders. AB - AIMS: To estimate and test the difference in rates of violent and non-violent crime during medicated and non-medicated methadone treatment episodes. DESIGN, SETTING AND PARTICIPANTS: The study involved linkage of population level administrative data (health and justice) for all individuals (n = 14 530) in British Columbia, Canada with a history of conviction and who filled a methadone prescription between 1 January 1998 and 31 March 2015. Methadone maintenance treatment was the primary independent variable and was treated as a time-varying exposure. Each participant's follow-up (mean: 8 years) was divided into medicated (methadone was dispensed) and non-medicated (methadone was not dispensed) periods with mean durations of 3.3 and 4.6 years, respectively. MEASUREMENTS: Socio demographics of participants were examined along with the main outcomes of violent and non-violent offences. FINDINGS: During the first 2 years of treatment (<= 2.0 years), periods in which methadone was dispensed were associated with a 33% lower rate of violent crime [0.67 adjusted hazard ratio (AHR), 95% confidence intervals (CI) = 0.59, 0.76] and a 35% lower rate of non-violent crime (0.65 AHR, 95% CI = 0.62, 0.69) compared with non-medicated periods. This equates to a risk difference of 3.6 (95% CI = 2.6, 4.4) and 37.2 (95% CI = 33.0, 40.4) fewer violent and non-violent offences per 100 person-years, respectively. Significant but smaller protective effects of dispensed methadone were observed across longer treatment intervals (2.0 to <= 5.0 years, 5.0 to <= 10.0 years). CONCLUSIONS: Among a cohort of Canadian offenders, rates of violent and non-violent offending were lower during periods when individuals were dispensed methadone compared with periods in which they were not dispensed methadone. PMID- 28987069 TI - Is zebrafish (Danio rerio) a tool for human-like metabolism study? AB - One of the greatest challenges in anti-doping science is the large number of substances available and the difficulty in finding the best analytical targets to detect their misuse. Therefore, metabolism studies involving prohibited substances are fundamental. However, metabolism studies in humans could face an important ethical bottleneck, especially for non-approved substances. An emerging model for metabolism assessment is the zebrafish, due to its genetic similarities with humans. In the present study, the ability of adult zebrafish to produce metabolites of sibutramine and stanozolol, substances with a well-known metabolism that are widely used as doping agents in sports, was evaluated. They represent 2 of the most abused classes of doping agents, namely, stimulants and anabolic steroids. These are classes that have been receiving attention because of the upsurge of synthetic analogues, for which the side effects in humans have not been assessed. The samples collected from the zebrafish tank water were hydrolysed, extracted by solid-phase extraction, and analysed by liquid chromatography with high resolution mass spectrometry (LC-HRMS). Adult zebrafish could produce several sibutramine and stanozolol metabolites, including demethylated, hydroxylated, dehydroxylated, and reduced derivatives, all of which have already been detected in human urine. This study demonstrates that adult zebrafish can absorb, oxidise, and excrete several metabolites in a manner similar to humans. Therefore, adult zebrafish seem to be a very promising tool to study human-like metabolism when aiming to find analytical targets for doping control. Copyright (c) 2017 John Wiley & Sons, Ltd. PMID- 28987070 TI - Impulsivity predicts poorer improvement in quality of life during early treatment for people with methamphetamine dependence. AB - BACKGROUND AND AIMS: Methamphetamine dependence is associated with heightened impulsivity and diminished quality of life, but the link between impulsivity and changes in quality of life during treatment has not been examined. We aimed to investigate how different elements of impulsivity predict change in quality of life in the 6 weeks after engaging in treatment. DESIGN: Longitudinal, observational cohort study. SETTING: Public and private detoxification and rehabilitation facilities in metropolitan Melbourne, Australia. PARTICIPANTS: One hundred and eight individuals with methamphetamine dependence (81 male) tested within 3 weeks of commencing treatment; 80 (74%) were followed-up at 6 weeks. MEASUREMENTS: The Continuous Performance Test-2 measured impulsive action (cognitive and motor impulsivity); the Delay Discounting Task measured impulsive choice. Quality of life was measured with the World Health Organization Quality of Life Scale-Brief, which includes social, psychological, physical and environment domains. Control variables included age, gender, estimated IQ, depression severity score, methamphetamine dependence severity score, cannabis dependence severity score and treatment modality. FINDINGS: We found that all three forms of impulsivity were significant predictors of change in the social domain: motor impulsivity (beta = -0.54, P = 0.013), cognitive impulsivity (beta = -0.46, P = 0.029) and impulsive choice (beta = -0.26, P = 0.019). Change in the psychological domain was predicted significantly by motor impulsivity (beta = 0.45, P = 0.046). Control variables of age and depression were associated significantly with changes in the physical domain. CONCLUSIONS: In Australian methamphetamine-dependent individuals, elevated impulsivity predicts lower improvement of social and psychological quality of life in the first 6-9 weeks of treatment. PMID- 28987071 TI - The spreaded gracilis flap revisited: Comparing outcomes in lower limb reconstruction. AB - BACKGROUND: In lower limb reconstruction, the free gracilis muscle flap is usually chosen for coverage of small- to medium-sized defects. Aim of this study was a re-appraisal regarding the reconstructive indications of the gracilis muscle flap with a focus on postoperative complications in order to evaluate if it can also be routinely used to reconstruct large-size lower limb defects. METHODS: A total of 204 patients underwent free gracilis muscle transfers for lower limb reconstruction at our institution. Cases were divided according to the size of the defect into two groups (<150 cm2 versus >=150 cm2 ). The small- to medium defect size group included 150 patients and the large defect size group included 54 patients. In the large defect size group, the muscle was enlarged as needed by careful dissection of the epimysium and all connective tissue surrounding the intrinsic vessels under loupe magnification to protect the muscle perfusion. Surgical complications were accounted for and the two groups compared accordingly. RESULTS: Overall, there were no significant differences between the two groups of patients regarding the rate of major (15.72% versus 10.91%; P = .506) and minor surgical complications (6.92% versus 3.64%; P = .522). The total percentage of flap losses in the small to medium defect size group was 5.03%. There were no total flap losses in the large defect size group (P = .117). CONCLUSION: The use of the spreaded gracilis flap provides a valuable option for the microsurgeon, especially also to reconstruct large size lower limb defects. PMID- 28987072 TI - Adult Use of Complementary and Integrative Approaches to Improve Athletic Performance. AB - : Context * In the United States in 2007, approximately 38% of adults, or 4 in 10, used some form of complementary and alternative medicine (CAM). An area in which little is known is the personal integration of CAM therapies by those individuals seeking to improve athletic performance. Objectives * The study intended to assess the use of integrative care by adult athletes in the United States as well as their satisfaction with it, as reported in the 2012 National Health Interview Survey (NHIS). Design * A secondary analysis of the data from the Adult Alternative Health/Complementary Medicine file of the 2012 NHIS was performed. SETTING: The analysis was performed at the Research Institute of Parker University (Dallas, TX, USA). Participants * The NHIS survey was a representative sample of Americans, with more than 30 000 respondents. Outcome Measures * National population estimates were generated for all related variables. The study assessed the likelihood that a respondent who reported use of a specific complementary and integrative therapy as their first top therapeutic modality to enhance sport or athletic performance had perceived it helpful compared with those who used it for other non-sport-related reasons. Results * Complementary and integrative therapies were used by more than 14 million adults (20.5%) to improve athletic performance, with 97.6% of them perceiving therapies as helpful. The most used therapies were yoga, herbal supplements, manipulation, and massage. The median age of those reporting specific use to improve athletic performance was slightly less than 38 y, and women were almost 3 times as likely as men to report therapies as helpful. Conclusions * Complementary and integrative therapies were used for improvement of athletic performance by respondents of the 2012 NHIS, with high satisfaction among users. Future research could evaluate athletic-specific use, adverse effects, physiological mechanisms that may exist for the modalities, and ways to integrate these methods better with traditional medical care. PMID- 28987073 TI - Human Microbiome as an Approach to Personalized Medicine. AB - Personalized medicine is an approach for medical decisions, practices, and interventions that considers individual variations in genes, environment, and lifestyle for each person. Regarding complex metabolic patterns associated with different diseases, characterizing unique metabolic patterns of each patient seems like a practical approach. We can imagine a future in which routinely analyzing the microbiome allows us to predict individualized responses to different foods and drugs. Microbiome analysis of individuals may be added to future routine personalized medicine protocols after comparing the costs and benefits of microbiome-sequencing technology. Moreover, improved understanding of the human microbiome could lead to the development of novel therapeutic strategies for different diseases. Potential therapeutic agents, such as personalized probiotic and prebiotic supplements, dietary interventions, and fecal microbiota transplantation that can be used to reshape the gut microbiome, represent a reasonable strategy in an era of personalized medicine. PMID- 28987074 TI - Combination of Rheum ribes and Metformin Against Diabetes, Thermal Hyperalgesia, and Tactile Allodynia in a Mice Model. AB - Context * The prevalence of diabetes mellitus (DM) is increasing. Because of its progressive nature, therapeutic shifts and combinations are often required to reduce the risk of glucose toxicity and avoid serious side effects. To treat DM and its related complications, a combination therapy may offer a promising remedy to counteract those issues. Objectives * The study was established to evaluate the phytochemical content of a standardized aqueous extract of Rheum ribes (RR) and to determine the antidiabetic, antihyperalgesic, and antimechanical allodynic effects of 50 mg/kg of RR alone, 25 mg/kg of metformin (MTF) alone, and a combination of the 2 substances (MTF+RR) in mice with alloxan-induced diabetes. Design * The research team designed an animal study. Setting * The study was performed at the facilities of the faculty of pharmacy at Beirut Arab University (Beirut, Lebanon). Animals * The animals were male, Swiss-Webster mice, weighing 22-30 g and aged 12-16 wk. Intervention * DM was induced in experimental animals by an IP injection of alloxan every 48 h for 3 injections at a total dose of 180 mg/kg. Substudy A measured the acute-0, 0.5, 2, and 6 h-and subchronic-1, 3, 5, and 8 d-effects of a water extract of the RR alone, of the MTF alone, and of the MTF+RR combination on blood-glucose levels (BGLs), body weights, and catalase (CAT) serum levels. The mice were divided into 6 groups of 7 mice each, and each group received various IP injections of the tested samples: (1) group 1, a vehicle control group of normal mice (NORM group) received sterile, cold, 0.9% saline; (2) group 2, a vehicle control group of diabetic mice (VEH group) received sterile, cold, 0.9% saline; (3) group 3, a positive control group of diabetic mice (GB group) received 5 mg/kg of glibenclamide; (4) group 4, an intervention group of diabetic mice (MTF group) received 25 mg/kg of MTF only; (5) group 5, an intervention group of diabetic mice (RR group) received 50 mg/kg of RR only; and (6) group 6, an intervention group (MTF+RR group) of diabetic mice received 25 mg/kg of MTF and 50 mg/kg of RR. Substudy B measured the subchronic-0, 2, 4, 6, and 8 wk-effects of the RR only, of the MTF only, and of the MTF+RR combination on the hot plate and tail flick latencies and on the von Frey paw withdrawal thresholds. Again, they were divided into 6 groups of 7 mice each (groups 7 through 12), and each group received various IP injections of the tested samples, with all of the groups receiving the same treatments as for substudy A, except that group 9, a positive control group of diabetic mice, received 10 mg/kg of tramadol. Outcome Measures * The BGLs of the mice were monitored acutely for 6 h and subchronically for 8 d. Glycated hemoglobin (HbA1c), inhibition of alpha-glucosidase, and effects on serum insulin were evaluated. Using tail flick, hot plate latencies, and von Frey paw withdrawal thresholds, thermal hyperalgesia and tactile allodynia were assessed. Using a natural antioxidant, in vivo antioxidant activity was used to evaluate CAT and lipid peroxide (LPO) levels. Results * The reductions in blood glucose, HbA1c, alpha-glucosidase, and LPO were statistically significant for the MTF+RR. The body weight, serum insulin, tail flick, hot plate latencies, paw withdrawal thresholds, and CAT increased significantly in diabetic mice treated with the combination. Consequently, the combination's potent inhibitory effect on alpha glucosidase and serum insulin elevation might be responsible for its hypoglycemic potential, whereas its antioxidant effects might be responsible for the amelioration of painful hyperalgesia and allodynia, suggesting that the combination has better antidiabetic and antinociceptive effects and fewer side effects than treatment with MTF alone. No adverse events were reported. Conclusion * When combined with MTF, RR might be a promising adjuvant for amelioration of DM and related nociceptive complications. PMID- 28987075 TI - Whooping Cough Alleviated by Homeopathic Medicines: A Case Report. AB - Context * Pertussis cough (whooping cough) is distressing due to the intensity and chronicity of its cough. No specific drugs are available that can alleviate the cough's intensity or significantly shorten its duration. Homeopathic medicines are used for a wide variety of medical conditions, including cough. Objective * The study investigated the benefits of homeopathic medicines for whooping cough, to alleviate the cough's intensity and to shorten its duration. Design * The current study was a case series of patients with whooping cough. Setting * The study took place at one of the suburban hospital clinics of the Ann & Robert H. Lurie Children's Hospital of Chicago (Chicago, IL, USA). Participants * Participants were 20 patients aged 21 mo to 20 y, of whom 11 were female and 18 were male, who visited the hospital clinic for treatment of the chronic cough that is characteristic of whooping cough. The details of the cases of 3 representative participants are highlighted in the text. Intervention * The 3 representative patients all received 1 dose weekly of a 30c dilution of homeopathic pertussinum and a 6c dilution of homeopathic Drosera 3 times daily. The homeopathic medicines most often used for the other participants were the same doses of pertussinum and Drosera. Outcome Measures * Verbal feedback from patient or family were obtained at the follow-up visits. Results * The intensity and duration of participant's coughs were alleviated within days to 1 wk in most cases. Conclusions * Homeopathic medicines can alleviate the intensity or reduce the duration of whooping cough, with no adverse effects. PMID- 28987076 TI - Potential Facilitators and Barriers to Awareness of N-of-1 Trials for Physicians in Traditional Chinese Medicine. AB - Context * N-of-1 trials are multiple crossover trials with randomized and blinded methods, conducted with a single participant to evaluate the effectiveness and safety of a therapy. They can be a helpful tool for enriching clinical research for traditional Chinese medicine (TCM), but the approach has gained little traction in TCM. Information is needed before supporters of the trials can pursue a change to that status. Objective * The study intended to obtain data needed to support TCM clinicians' adoption of N-of-1 trials. Methods * TCM clinicians were interviewed using a dedicated questionnaire between May 15, 2014, and July 31, 2014. Setting * The study took place at 4 teaching hospitals (Lanzhou City, China). Participants * Participants were TCM clinicians at the 4 hospitals. Outcome Measures * The survey included questions to obtain information on (1) the various methods that the TCM physicians used to obtain information about how to develop and conduct clinical trials, (2) their knowledge and experience with traditional clinical trials, (3) their awareness of the concept and methodology of N-of-1 trials, and (4) their needs and willingness to receive training about such trials. Descriptive statistics were used. Results * One-hundred-and-six clinicians, with a median age of 32 +/- 9 y, participated in the survey. Most received information on research methods from a medical database (77%) or academic conferences (65%). Eighty-two percent of the clinicians had read papers about clinical trials, and 84% of the material read were medical articles in Mandarin. Of the participants, 57% had designed and carried out clinical trials during the 5 y before the survey, and among those participants, 26% had performed randomized controlled trials (RCTs), 28% had carried out retrospective studies, 16% had conducted observational studies, and 30% had completed case reports. For those studies, the results of 7% had been published in the Science Citation Index (SCI), 47% in the Chinese Science Citation Database (CSCD), and 31% in provincial journals; 15% were unpublished. Only 37% had heard of an N-of-1 trial, and only 5% understood what the term means. Most intermediate clinicians thought it is necessary to train different groups of clinicians using N-of-1 trials that included clinicians and patients. Conclusions * The results highlight the possible interest of TCM clinicians in the methods of N-of-1 trials; meanwhile, the study's data stress the need for appropriate medical education and recommendations based on available evidence. Further efforts in the area should emphasize the benefits for patients and funders. The training is necessary in TCM clinical practice to improve the evidence quality of studies on TCM. PMID- 28987077 TI - Remission of Schizoaffective Disorder Using Homeopathic Medicine: 2 Case Reports. AB - Context * Research on the schizophrenia spectrum is primarily focused on pharmaceutical interventions, although alternative treatments have been gaining increasing popularity in recent years because patients are seeking treatments that are effective and have reduced side effects. A significant body of evidence already exists supporting the effectiveness of homeopathy to treat a wide array of illnesses. Objective * The research team intended to demonstrate the need for using both alternative and conventional treatments to improve clinical outcomes in the treatment of schizoaffective disorder. Design * The research team performed 2 case studies. Setting * The study took place at Arizona Natural Health Center (Tempe, AZ, USA), an outpatient clinic where Dr Tara Peyman worked as a naturopathic doctor from 2008 to 2014. Participants * The participants were a 23-y-old female (case 1) and a 34-y-old female (case 2), both of whom had been diagnosed with schizoaffective disorder of the bipolar type. Intervention * Individualized homeopathic treatment was initiated for the 2 patients, who previously had received medication of atypical antipsychotics and mood stabilizers. Outcome Measures * A Likert scale was used to evaluate the intensity of each patient's symptoms at each follow-up, based on self-reporting, using a scale from 1 to 10, with a score of 10 being the highest. Results * During the course of treatment, both patients' symptoms normalized, and they regained their ability to hold jobs, attend school, and maintain healthy relationships with their families and partners while requiring fewer pharmaceutical interventions. Conclusions * The 2 current case reports demonstrate a successful integrative approach to the treatment of schizoaffective disorder. They illustrate the value of individualized homeopathic prescriptions with proper case management in the successful treatment of that disorder. Future large-scale, double-blind, placebo controlled studies should investigate individualized homeopathic treatments for mental health concerns, because the diseases cause great economic and social burden. PMID- 28987078 TI - Brief Report: Stability and Chemical Characteristics of Injectable Ascorbic Acid for Patients With Cancer. AB - Context * Intravenous ascorbic acid (IVAA) has been used extensively as part of the management plan for cancer patients in various medical clinics throughout the United States. The current research team has evaluated its effectiveness in patients with cancer as part of an ongoing research program. However, no data are available that support the chemical stability of intravenously injectable ascorbic acid (AA) to ensure its safety and efficacy in that patient population. Its clinical use as well as its use in research conducted in US Food and Drug Administration-approved clinical trials require validation of its stability. Objective * The study intended to evaluate the chemical stability of the compounded IVAA that it prepares. Design * The research team conducted a stability analysis within a 6-h period, a period longer than the time required for most infusions, which typically take approximately 2 h. The study evaluated the stability of AA intravenous sets, which are compounded solutions for clinical or hospital use. The IVAA was prepared in sterile water, together with magnesium chloride (MgCl) and calcium gluconate (CaGluc) as buffers. Setting * The study took place at the Marcus Institute of Integrative Health at Thomas Jefferson University (Philadelphia, PA, USA). Outcome Measures * The study was performed for 2 dosages of an infusion set: 75 g and 100 g of IVAA. Interval testing included pH, particulate matter by light obscuration, and high-performance liquid chromatography assay. Analyses were performed at baseline and at 2-, 4-, and 6-h test intervals. Results * The results demonstrated that IVAA remained highly stable throughout the 6-h period. It also passed the US Pharmacopeia's criteria for pH and particulates when used with a 0.2 u filter. Conclusions * These data suggest that IVAA, when prepared with sterile water, in addition to MgCl and CaGluc, is highly stable and safe to use in patients for up to 6 h after preparation. PMID- 28987079 TI - Effectiveness of Biofield Therapy for Patients Diagnosed With Fibromyalgia. AB - Context * Fibromyalgia (FM) is a disorder with an unknown etiology; symptoms include physical and psychological stress, widespread chronic pain, insomnia, and depression. Mind-body medicine and aerobic exercise have shown positive effects for symptom control. Several studies have reported positive effects for biofield therapy for FM, but when other studies have compared the treatment with a sham control, they have not found those beneficial effects. Objective * The study intended to examine the effects of a biofield therapy called Okada purifying therapy on patients' FM symptoms. Design * An open-label, self-controlled study was conducted with 2 groups of FM patients. Setting * The study was conducted at an integrative medicine clinic in Portugal. Participants * Twelve patients, aged 25 to 59 y, with symptoms of FM for the 3 mo before the study, participated. Participants agreed not to receive any new treatment other than the intervention throughout the study as a condition for participation. Intervention * Participants received 50 min of biofield therapy 2 */wk for 3 mo, either during the first half of the 6-mo study for group A or the second half for group B. The second half of the study was designated as a sham control for group A, and the first half of the study was designated as a sham control for group B. Outcome Measures * Measures included the Beck depression inventory (BDI), the fibromyalgia impact questionnaire (FIQ), the tender point index (TPI), and changes in the dosage of prescribed medication. Results * A significant change was observed for scores in the FIQ (P = .027), BDI (P = .027), and TPI (P = .027) in the second group of patients who received the intervention in the second half of the 6-mo study. Seven of 11 participants taking prescribed medications reduced their dosage. Conclusion * Biofield therapy may help reduce symptoms of depression, chronic widespread pain, and tenderness among patients suffering from FM. Larger studies with rigorous designs are required for further accurate evaluation. PMID- 28987080 TI - Review of Literature on Low-level Laser Therapy Benefits for Nonpharmacological Pain Control in Chronic Pain and Osteoarthritis. AB - Introduction * Low-level laser therapy (LLLT) is a form of light therapy that triggers biochemical changes within cells. Photons are absorbed by cellular photoreceptors, triggering chemical alterations and potential biochemical benefits to the human body. LLLT has been used in pain management for years and is also known as cold laser therapy, which uses low-frequency continuous laser of typically 600 to 1000 nm wavelength for pain reduction and healing stimulation. Many studies have demonstrated analgesic and anti-inflammatory effects provided by photobiomodulation in both experimental and clinical trials. Objective * The purpose of this research article was to present a summary of the possible pain management benefits of LLLT. Results * In cold laser therapy, coherent light of wavelength 600 to 1000 nm is applied to an area of concern with hope for photo stimulating the tissues in a way that promotes and accelerates healing. This is evidenced by the similarity in absorption spectra between oxidized cytochrome c oxidase and action spectra from biological responses to light. LLLT, using the properties of coherent light, has been seen to produce pain relief and fibroblastic regeneration in clinical trials and laboratory experiments. LLLT has also been seen to significantly reduce pain in the acute setting; it is proposed that LLLT is able to reduce pain by lowering the level of biochemical markers and oxidative stress, and the formation of edema and hemorrhage. Many studies have demonstrated analgesic and anti-inflammatory effects provided by photobiomodulation in both experimental and clinical trials. Conclusion * Based on current research, the utilization of LLLT for pain management and osteoarthritic conditions may be a complementary strategy used in clinical practice to provide symptom management for patients suffering from osteoarthritis and chronic pain. PMID- 28987081 TI - Variations in the Anterolateral Thigh Flap's Vascular Anatomy in African Americans. AB - BACKGROUND: Variations in anterolateral thigh (ALT) arterial anatomy are well documented. Ethnicity is a known risk factor for vascular variation in several organ systems, but its impact on ALT anatomy has not been studied. Anecdotally, we observed frequent ALT arterial variation in African American (AA) patients. We thus hypothesized that AA patients have higher rates of anomalous branching. MATERIALS AND METHODS: A total of 277 computed tomography angiograms (513 lower extremities) captured between May 1, 2013 and May 31, 2015 at a tertiary academic medical center were retrospectively analyzed to determine ALT arterial branching. Patient records were examined to ascertain demographics. Data were analyzed using descriptive statistics and multinomial logistic regression. RESULTS: Males comprised 84.5%. Ethnic distribution was 55.2% AA and 36.5% Caucasian. The descending branch of the lateral circumflex femoral artery (dLCFA) originated from non-LCFA arteries (deep femoral, common femoral, or superficial femoral arteries) in 18.9% of Caucasian versus 9.1% of AA (odds ratio [OR]: 2.28; 95% confidence interval [CI]: 1.33-3.93, p < 0.01). An oblique branch was identified in 41.1% of Caucasian versus 51.9% of AA (OR: 1.56; 95% CI: 1.08-2.24, p = 0.02). Ethnicity was the only driving factor of dLCFA and oblique branch of the LCFA (oLCFA) anatomy (Wald chi-square: 14 and 11, p = 0.03 and 0.02, respectively). CONCLUSIONS: Ethnicity significantly affects ALT arterial anatomy. AA are more likely to have classical dLCFA branching with a fourth oLCFA branch. A flap with an unrecognized oLCFA-dominant supply places patients at a higher risk for flap failure and loss. We recommend preoperative imaging before undertaking an ALT flap reconstruction. PMID- 28987082 TI - Sternal Anomalies in Asymptomatic Patients after Median Sternotomy and Potential Influencing Factors. AB - BACKGROUND: We aimed to assess asymptomatic patients who had open-heart surgery with median sternotomy for potential sternal anomalies (SA), their related patient-specific risk factors, and treatment options for the prevention of SA. METHODS: Multiplanar CT scans (CTs) from 131 asymptomatic consecutive patients were analyzed retrospectively. Of these, 83 underwent CABG (63.4%), and 48 had aortic valve (AV) procedures via median sternotomy. Sternal bone healing was analyzed for SA and their exact location. RESULTS: In total, 49 SA were identified in 42 (32.1%) patients; 65% SA were found in the manubrium (n = 32). Five hundred thirty-two wires were implanted (4.2 +/- 0.5 wires/patient), out of which 96.1% (n = 511) were figure 8 wires. There was no difference between normal and abnormal sterna with regard to the number of wires used for sternal closure (4.2 +/- 0.5 vs. 4.3 +/- 0.6, p = ns). The distance between wire placement to the proximal edge of the manubrium in normal and abnormal sterna was comparable (11.2 +/- 4.2 vs. 10.9 +/- 4.8 mm, p = ns). Patients who underwent CABG had a significantly higher risk for SA (OR = 2.4, p <= 0.05, 95% CI [1.2-4.9]). The use of BIMA (OR = 4.4, p <= 0.05, 95% CI [1.1-17.9]) and body mass index (BMI) > 31 kg/m2 (OR = 3.4, p <= 0.01, 95% CI [1.4-8.3]) significantly increased the risk of SA. CONCLUSION: At least 30% of patients were at an increased risk for SA after receiving a median sternotomy. CABG, use of BIMA, and a BMI > 30 kg/m2 were potential risk factors for the development of SA and warrant close clinical follow-up. Sternal plate fixation, particularly in the manubrium, could be beneficial in such patients. PMID- 28987083 TI - First passage, looping, and direct transition in expanding and narrowing tubes: Effects of the entropy potential. AB - We study transitions of diffusing particles between the left and right ends of expanding and narrowing conical tubes. In an expanding tube, such transitions occur faster than in the narrowing tube of the same length and radius variation rate. This happens because the entropy potential pushes the particle towards the wide tube end, thus accelerating the transitions in the expanding tube and slowing them down in the narrowing tube. To gain deeper insight into how the transitions occur, we divide each trajectory into the direct-transit and looping segments. The former is the final part of the trajectory, where the particle starting from the left tube end goes to the right end without returning to the left one. The rest of the trajectory is the looping segment, where the particle, starting from the left tube end, returns to this end again and again until the direct transition happens. Our focus is on the durations of the two segments and their sum, which is the duration of the particle first passage between the left and right ends of the tube. We approach the problem using the one-dimensional description of the particle diffusion along the tube axis in terms of the modified Fick-Jacobs equation. This allows us to derive analytical expressions for the Laplace transforms of the probability densities of the first-passage, direct-transit, and looping times, which we use to find the mean values of these random variables. Our results show that the direct transits are independent of the entropy potential and occur as in free diffusion. However, this "free diffusion" occurs with the effective diffusivity entering the modified Fick Jacobs equation, which is smaller than the particle diffusivity in a cylindrical tube. This is the only way how the varying tube geometry manifests itself in the direct transits. Since direct-transit times are direction-independent, the difference in the first-passage times in the tubes of the two types is due to the difference in the durations of the looping segments in the expanding and narrowing tubes. Obtained analytical results are supported by three-dimensional Brownian dynamics simulations. PMID- 28987084 TI - Formation and decomposition of CO2-filled ice. AB - Recently it was shown that CO2-filled ice is formed upon compression of CO2 clathrate hydrate. Here we show two alternative routes of its formation, namely, by decompression of CO2/ice VI mixtures at 250 K and by isobaric heating of CO2/high-density amorphous ice mixtures at 0.5-1.0 GPa above 200 K. Furthermore, we show that filled ice may either transform into the clathrate at an elevated pressure or decompose to "empty" hexagonal ice at ambient pressure and low temperature. This complements the literature studies in which decomposition to ice VI was favoured at high pressures and low temperatures. PMID- 28987086 TI - First passage times for multiple particles with reversible target-binding kinetics. AB - We investigate the first passage problem for multiple particles that diffuse towards a target, partially adsorb there, and then desorb after a finite exponentially distributed residence time. We search for the first time when m particles undergoing such reversible target-binding kinetics are found simultaneously on the target that may trigger an irreversible chemical reaction or a biophysical event. Even if the particles are independent, the finite residence time on the target yields an intricate temporal coupling between particles. We compute analytically the mean first passage time (MFPT) for two independent particles by mapping the original problem to higher-dimensional surface-mediated diffusion and solving the coupled partial differential equations. The respective effects of the adsorption and desorption rates on the MFPT are revealed and discussed. PMID- 28987085 TI - Communication: Broad manifold of excitonic states in light-harvesting complex 1 promotes efficient unidirectional energy transfer in vivo. AB - In photosynthetic organisms, the pigment-protein complexes that comprise the light-harvesting antenna exhibit complex electronic structures and ultrafast dynamics due to the coupling among the chromophores. Here, we present absorptive two-dimensional (2D) electronic spectra from living cultures of the purple bacterium, Rhodobacter sphaeroides, acquired using gradient assisted photon echo spectroscopy. Diagonal slices through the 2D lineshape of the LH1 stimulated emission/ground state bleach feature reveal a resolvable higher energy population within the B875 manifold. The waiting time evolution of diagonal, horizontal, and vertical slices through the 2D lineshape shows a sub-100 fs intra-complex relaxation as this higher energy population red shifts. The absorption (855 nm) of this higher lying sub-population of B875 before it has red shifted optimizes spectral overlap between the LH1 B875 band and the B850 band of LH2. Access to an energetically broad distribution of excitonic states within B875 offers a mechanism for efficient energy transfer from LH2 to LH1 during photosynthesis while limiting back transfer. Two-dimensional lineshapes reveal a rapid decay in the ground-state bleach/stimulated emission of B875. This signal, identified as a decrease in the dipole strength of a strong transition in LH1 on the red side of the B875 band, is assigned to the rapid localization of an initially delocalized exciton state, a dephasing process that frustrates back transfer from LH1 to LH2. PMID- 28987087 TI - Detection and structural characterization of nitrosamide H2NNO: A central intermediate in deNOx processes. AB - The structure and bonding of H2NNO, the simplest N-nitrosamine, and a key intermediate in deNOx processes, have been precisely characterized using a combination of rotational spectroscopy of its more abundant isotopic species and high-level quantum chemical calculations. Isotopic spectroscopy provides compelling evidence that this species is formed promptly in our discharge expansion via the NH2 + NO reaction and is collisionally cooled prior to subsequent unimolecular rearrangement. H2NNO is found to possess an essentially planar geometry, an NNO angle of 113.67(5) degrees , and a N-N bond length of 1.342(3) A; in combination with the derived nitrogen quadrupole coupling constants, its bonding is best described as an admixture of uncharged dipolar (H2N-N=O, single bond) and zwitterion (H2N+=N-O-, double bond) structures. At the CCSD(T) level, and extrapolating to the complete basis set limit, the planar geometry appears to represent the minimum of the potential surface, although the torsional potential of this molecule is extremely flat. PMID- 28987088 TI - Rate of hemifusion diaphragm dissipation and ability to form three-junction bound HD determined by lipid composition. AB - Though the hemifusion diaphragm (HD) is widely accepted as an intermediate in bilayer membrane fusion, lipid contributions toward HD stability and dynamics are still not fully understood. In this paper, we study large, binary, protein-free HD systems at varying compositions of negative intrinsic curvature (NIC) lipids using molecular dynamics (MD) simulations of a solvent-free coarse-grained lipid model. Under MD, initially created HDs are found to relax to three major end states depending on the composition and lipid intrinsic curvature. Low compositions of NIC lipids or weak intrinsic curvature result in double-bilayer end states, and moderate compositions of moderate to strong NIC lipids result in metastable fusion pores. Importantly, high compositions of moderate NIC lipids result in a metastable HD that persists beyond MUs time scales. NIC lipids stabilize the HD by filling the junction core around the HD. Sorting of NIC lipids toward the three-junction region occurs in fused-endpoint systems, but no significant sorting was seen in systems that end in a double bilayer indicating that high line tension at the triple junction drives HD dissipation faster than sorting can enrich that junction enough to lower that line tension. The appearance of three end states dependent on the NIC lipid composition highlights the necessity of NIC lipids for non-leaky fusion. PMID- 28987089 TI - Spin switch in iron phthalocyanine on Au(111) surface by hydrogen adsorption. AB - The manipulation of spin states at the molecular scale is of fundamental importance for the development of molecular spintronic devices. One of the feasible approaches for the modification of a molecular spin state is through the adsorption of certain specific atoms or molecules including H, NO, CO, NH3, and O2. In this paper, we demonstrate that the local spin state of an individual iron phthalocyanine (FePc) molecule adsorbed on an Au(111) surface exhibits controllable switching by hydrogen adsorption, as evidenced by using first principles calculations based on density functional theory. Our theoretical calculations indicate that different numbers of hydrogen adsorbed at the pyridinic N sites of the FePc molecule largely modify the structural and electronic properties of the FePc/Au(111) composite by forming extra N-H bonds. In particular, the adsorption of one or up to three hydrogen atoms induces a redistribution of charge (spin) density within the FePc molecule, and hence a switching to a low spin state (S = 1/2) from an intermediate spin state (S = 1) is achieved, while the adsorption of four hydrogen atoms distorts the molecular conformation by increasing Fe-N bond lengths in FePc and thus breaks the ligand field exerted on the Fe 3d orbitals via stronger hybridization with the substrate, leading to an opposite switching to a high-spin state (S = 2). These findings obtained from the theoretical simulations could be useful for experimental manipulation or design of single-molecule spintronic devices. PMID- 28987090 TI - Conceptual DFT analysis of the fragility spectra of atoms along the minimum energy reaction coordinate. AB - Theoretical justification has been provided to the method for monitoring the sequence of chemical bonds' rearrangement along a reaction path, by tracing the evolution of the diagonal elements of the Hessian matrix. Relations between the divergences of Hellman-Feynman forces and the energy and electron density derivatives have been demonstrated. By the proof presented on the grounds of the conceptual density functional theory formalism, the spectral amplitude observed on the atomic fragility spectra [L. Komorowski et al., Phys. Chem. Chem. Phys. 18, 32658 (2016)] reflects selectively the electron density modifications in bonds of an atom. In fact the spectral peaks for an atom reveal changes of the electron density occurring with bonds creation, breaking, or varying with the reaction progress. PMID- 28987091 TI - Experimental and theoretical studies of the reactions of ground-state sulfur atoms with hydrogen and deuterium. AB - The gas-phase kinetics of S(3P) atoms with H2 and D2 have been studied via the laser flash photolysis-resonance fluorescence technique. S atoms were generated by pulsed photolysis of CS2 at 193 nm and monitored by time-resolved fluorescence at 181 nm. The rate coefficients for H2 (k1) and D2 (k2), respectively, are summarized as k1(600-1110 K) = 3.0 * 10-9 exp-1.317*105-2.703*107K/T8.314 T/K cm3 molecule-1 s-1 and k2(770-1110 K) = 2.2 * 10-14 (T/298 K)3.55 exp(-5420 K/T) cm3 molecule-1 s-1. Error limits are discussed in the text. The rate coefficients for formation of SH(SD) + H(D) on a newly developed triplet potential energy surface were characterized via ring polymer molecular dynamics and canonical variational transition-state theory. There is excellent agreement above about 1000 K between theory and experiment. At lower temperatures, the experimental rate coefficient is substantially larger than the results computed for the adiabatic reaction, suggesting a significant role for intersystem crossing to the singlet potential energy surface at lower temperatures. PMID- 28987092 TI - Phase diagram of two-dimensional hard rods from fundamental mixed measure density functional theory. AB - A density functional theory for the bulk phase diagram of two-dimensional orientable hard rods is proposed and tested against Monte Carlo computer simulation data. In detail, an explicit density functional is derived from fundamental mixed measure theory and freely minimized numerically for hard discorectangles. The phase diagram, which involves stable isotropic, nematic, smectic, and crystalline phases, is obtained and shows good agreement with the simulation data. Our functional is valid for a multicomponent mixture of hard particles with arbitrary convex shapes and provides a reliable starting point to explore various inhomogeneous situations of two-dimensional hard rods and their Brownian dynamics. PMID- 28987093 TI - Presence of global and local alpha-relaxations in an alkyl phosphate glass former. AB - The dynamics of a molecular glass former, tributyl phosphate (TBP), with an alkyl phosphate structure (three alkyl branches emanating from a polar core of PO4) is studied in the supercooled regime by dielectric and thermal (or enthalpic) relaxations. The dielectric fragility index md and the stretching exponent betad of the Kohlrausch-Williams-Watts correlation function are determined. Analyses of the enthalpic relaxation data by the Tool-Narayanaswamy-Moynihan-Hodge formalism yield the enthalpic fragility index mH and stretching exponent betaH. The large difference between the dielectric md and the enthalpic mH, as well as between betad and betaH, is a remarkable finding. The differences are interpreted by the formation of molecular self-assemblies. The interpretation is supported by the quite comparable fragility determined by viscosity and the enthalpic relaxation. The Kirkwood factor calculated at low temperatures is also consistent with the interpretation. The results suggest that the enthalpic relaxation involving the motions of all parts of TBP is global, while the dielectric relaxation detects the local rotation, which might originate from the rotation of the dipole moment of the core. The presence of two structural alpha-relaxations, one global and one local, with a large difference in dynamics is revealed for the first time in a molecular glass former. PMID- 28987094 TI - Support for the existence of invertible maps between electronic densities and non analytic 1-body external potentials in non-relativistic time-dependent quantum mechanics. AB - Provided the initial state, the Runge-Gross theorem establishes that the time dependent (TD) external potential of a system of non-relativistic electrons determines uniquely their TD electronic density, and vice versa (up to a constant in the potential). This theorem requires the TD external potential and density to be Taylor-expandable around the initial time of the propagation. This paper presents an extension without this restriction. Given the initial state of the system and evolution of the density due to some TD scalar potential, we show that a perturbative (not necessarily weak) TD potential that induces a non-zero divergence of the external force-density, inside a small spatial subset and immediately after the initial propagation time, will cause a change in the density within that subset, implying that the TD potential uniquely determines the TD density. In this proof, we assume unitary evolution of wavefunctions and first-order differentiability (which does not imply analyticity) in time of the internal and external force-densities, electronic density, current density, and their spatial derivatives over the small spatial subset and short time interval. PMID- 28987095 TI - Erratum: "Targeting excited states in all-trans polyenes with electron-pair states" [J. Chem. Phys. 145, 234105 (2016)]. PMID- 28987096 TI - Effect of chain stiffness for semiflexible macromolecules in array of cylindrical nanoposts. AB - Equilibrium conformation of a semiflexible macromolecule in an array of nanoposts exhibits a non-monotonic behavior both at variation of the chain stiffness and increased crowding imposed by nanoposts. This is a result of the competition between the axial chain extension in channel-like interstitial volumes between nanoposts and the chain partitioning among these volumes. The approximation of a nanopost array as a combination of a quasi-channel and a quasi-slit like geometry semi-qualitatively explains the behavior of a chain in the array. In this approximation, the interstitial spaces are viewed as being of the channel geometry, while the passages between two adjacent posts are viewed as being of the slit geometry. Interestingly, the stiffer chains tend to penetrate more readily through the passage apertures, in the direction perpendicular to the post axes, and thus to occupy more interstitial volumes. This is consistent with the prediction of the free-energy penalty that is lower for a stiffer chain at strong slit-like confinement. These findings can find applications in the control of macromolecular conformations in recent nanotechnological techniques with bio macromolecules such as a DNA. PMID- 28987097 TI - Multi-dimensional virtual system introduced to enhance canonical sampling. AB - When an important process of a molecular system occurs via a combination of two or more rare events, which occur almost independently to one another, computational sampling for the important process is difficult. Here, to sample such a process effectively, we developed a new method, named the "multi dimensional Virtual-system coupled Monte Carlo (multi-dimensional-VcMC)" method, where the system interacts with a virtual system expressed by two or more virtual coordinates. Each virtual coordinate controls sampling along a reaction coordinate. By setting multiple reaction coordinates to be related to the corresponding rare events, sampling of the important process can be enhanced. An advantage of multi-dimensional-VcMC is its simplicity: Namely, the conformation moves widely in the multi-dimensional reaction coordinate space without knowledge of canonical distribution functions of the system. To examine the effectiveness of the algorithm, we introduced a toy model where two molecules (receptor and its ligand) bind and unbind to each other. The receptor has a deep binding pocket, to which the ligand enters for binding. Furthermore, a gate is set at the entrance of the pocket, and the gate is usually closed. Thus, the molecular binding takes place via the two events: ligand approach to the pocket and gate opening. In two dimensional (2D)-VcMC, the two molecules exhibited repeated binding and unbinding, and an equilibrated distribution was obtained as expected. A conventional canonical simulation, which was 200 times longer than 2D-VcMC, failed in sampling the binding/unbinding effectively. The current method is applicable to various biological systems. PMID- 28987098 TI - Restricted lithium ion dynamics in PEO-based block copolymer electrolytes measured by high-field nuclear magnetic resonance relaxation. AB - The intrinsic ionic conductivity of polyethylene oxide (PEO)-based block copolymer electrolytes is often assumed to be identical to the conductivity of the PEO homopolymer. Here, we use high-field 7Li nuclear magnetic resonance (NMR) relaxation and pulsed-field-gradient (PFG) NMR diffusion measurements to probe lithium ion dynamics over nanosecond and millisecond time scales in PEO and polystyrene (PS)-b-PEO-b-PS electrolytes containing the lithium salt LiTFSI. Variable-temperature longitudinal (T1) and transverse (T2) 7Li NMR relaxation rates were acquired at three magnetic field strengths and quantitatively analyzed for the first time at such fields, enabling us to distinguish two characteristic time scales that describe fluctuations of the 7Li nuclear electric quadrupolar interaction. Fast lithium motions [up to O(ns)] are essentially identical between the two polymer electrolytes, including sub-nanosecond vibrations and local fluctuations of the coordination polyhedra between lithium and nearby oxygen atoms. However, lithium dynamics over longer time scales [O(10 ns) and greater] are slower in the block copolymer compared to the homopolymer, as manifested experimentally by their different transverse 7Li NMR relaxation rates. Restricted dynamics and altered thermodynamic behavior of PEO chains anchored near PS domains likely explain these results. PMID- 28987099 TI - Erratum: "Temperature dependence of the hydrated electron's excited-state relaxation. II. Elucidating the relaxation mechanism through ultrafast transient absorption and stimulated emission spectroscopy" [J. Chem. Phys. 147, 074504 (2017)]. PMID- 28987100 TI - The aug-cc-pVnZ-F12 basis set family: Correlation consistent basis sets for explicitly correlated benchmark calculations on anions and noncovalent complexes. AB - We have developed a new basis set family, denoted as aug-cc-pVnZ-F12 (or aVnZ-F12 for short), for explicitly correlated calculations. The sets included in this family were constructed by supplementing the corresponding cc-pVnZ-F12 sets with additional diffuse functions on the higher angular momenta (i.e., additional d-h functions on non-hydrogen atoms and p-g on hydrogen atoms), optimized for the MP2 F12 energy of the relevant atomic anions. The new basis sets have been benchmarked against electron affinities of the first- and second-row atoms, the W4-17 dataset of total atomization energies, the S66 dataset of noncovalent interactions, the Benchmark Energy and Geometry Data Base water cluster subset, and the WATER23 subset of the GMTKN24 and GMTKN30 benchmark suites. The aVnZ-F12 basis sets displayed excellent performance, not just for electron affinities but also for noncovalent interaction energies of neutral and anionic species. Appropriate CABSs (complementary auxiliary basis sets) were explored for the S66 noncovalent interaction benchmark: between similar-sized basis sets, CABSs were found to be more transferable than generally assumed. PMID- 28987101 TI - Conjugating precision and acquisition time in a Doppler broadening regime by interleaved frequency-agile rapid-scanning cavity ring-down spectroscopy. AB - We propose a novel approach to cavity-ring-down-spectroscopy (CRDS) in which spectra acquired with a frequency-agile rapid-scanning (FARS) scheme, i.e., with a laser sideband stepped across the modes of a high-finesse cavity, are interleaved with one another by a sub-millisecond readjustment of the cavity length. This brings to time acquisitions below 20 s for few-GHz-wide spectra composed of a very high number of spectral points, typically 3200. Thanks to the signal-to-noise ratio easily in excess of 10 000, each FARS-CRDS spectrum is shown to be sufficient to determine the line-centre frequency of a Doppler broadened line with a precision of 2 parts over 1011, thus very close to that of sub-Doppler regimes and in a few-seconds time scale. The referencing of the probe laser to a frequency comb provides absolute accuracy and long-term reproducibility to the spectrometer and makes it a powerful tool for precision spectroscopy and line-shape analysis. The experimental approach is discussed in detail together with experimental precision and accuracy tests on the (30 012) <- (00 001) P12e line of CO2 at ~1.57 MUm. PMID- 28987102 TI - Force probe simulations using a hybrid scheme with virtual sites. AB - Hybrid simulations, in which a part of the system is treated with atomistic resolution and the remainder is represented on a coarse-grained level, allow for fast sampling while using the accuracy of atomistic force fields. We apply a hybrid scheme to study the mechanical unfolding and refolding of a molecular complex using force probe molecular dynamics (FPMD) simulations. The degrees of freedom of the solvent molecules are treated in a coarse-grained manner while atomistic resolution is retained for the solute. The coupling between the solvent and the solute is provided using virtual sites. We test two different common coarse-graining procedures, the iterative Boltzmann inversion method and the force matching procedure, and find that both methodologies give similar results. The results of the FPMD simulations are compared to all-atom simulations of the same system and we find that differences between these simulations and the ones using the hybrid scheme are in a similar range as the differences obtained when using different atomistic force fields. Thus, a hybrid scheme yields qualitatively correct results in the strong non-equilibrium situation the system is experiencing in FPMD simulations. PMID- 28987104 TI - Excitation energies from particle-particle random phase approximation with accurate optimized effective potentials. AB - The optimized effective potential (OEP) that gives accurate Kohn-Sham (KS) orbitals and orbital energies can be obtained from a given reference electron density. These OEP-KS orbitals and orbital energies are used here for calculating electronic excited states with the particle-particle random phase approximation (pp-RPA). Our calculations allow the examination of pp-RPA excitation energies with the exact KS density functional theory (DFT). Various input densities are investigated. Specifically, the excitation energies using the OEP with the electron densities from the coupled-cluster singles and doubles method display the lowest mean absolute error from the reference data for the low-lying excited states. This study probes into the theoretical limit of the pp-RPA excitation energies with the exact KS-DFT orbitals and orbital energies. We believe that higher-order correlation contributions beyond the pp-RPA bare Coulomb kernel are needed in order to achieve even higher accuracy in excitation energy calculations. PMID- 28987103 TI - Connections between variation principles at the interface of wave-function and density-functional theories. AB - A recently proposed variation principle [N. I. Gidopoulos, Phys. Rev. A 83, 040502(R) (2011)] for the determination of Kohn-Sham effective potentials is examined and extended to arbitrary electron-interaction strengths and to mixed states. Comparisons are drawn with Lieb's convex-conjugate functional, which allows for the determination of a potential associated with a given electron density by maximization, yielding the Kohn-Sham potential for a non-interacting system. The mathematical structure of the two functionals is shown to be intrinsically related; the variation principle put forward by Gidopoulos may be expressed in terms of the Lieb functional. The equivalence between the information obtained from the two approaches is illustrated numerically by their implementation in a common framework. PMID- 28987105 TI - Communication: A hydrogen-bonded difluorocarbene complex: Ab initio and matrix isolation study. AB - Structure and spectroscopic features of the CF2?HF complexes were studied by ab initio calculations at the CCSD(T) level and matrix isolation FTIR spectroscopy. The calculations predict three stable structures. The most energetically favorable structure corresponds to hydrogen bonding of HF to the lone pair of the C atom (the interaction energy of 3.58 kcal/mol), whereas two less stable structures are the H?F bonded complexes (the interaction energies of 0.30 and 0.24 kcal/mol). The former species was unambiguously characterized by the absorptions in the FTIR spectra observed after X-ray irradiation of fluoroform in a xenon matrix at 5 K. The corresponding features appear at 3471 (H-F stretching), 1270 (C-F symmetric stretching, shoulder), 1175 (antisymmetric C-F stretching), and 630 (libration) cm-1, in agreement with the computational predictions. To our knowledge, it is the first hydrogen-bonded complex of dihalocarbene. Possible weaker manifestations of the H?F bonded complexes were also found in the C-F stretching region; however, their assignment is tentative. The H?C bonded complex is protected from reaction yielding a fluoroform molecule by a remarkably high energy barrier (23.85 kcal/mol), so it may be involved in various chemical reactions. PMID- 28987106 TI - Removing the barrier to the calculation of activation energies: Diffusion coefficients and reorientation times in liquid water. AB - General approaches for directly calculating the temperature dependence of dynamical quantities from simulations at a single temperature are presented. The method is demonstrated for self-diffusion and OH reorientation in liquid water. For quantities which possess an activation energy, e.g., the diffusion coefficient and the reorientation time, the results from the direct calculation are in excellent agreement with those obtained from an Arrhenius plot. However, additional information is obtained, including the decomposition of the contributions to the activation energy. These results are discussed along with prospects for additional applications of the direct approach. PMID- 28987107 TI - Kinetic theory for DNA melting with vibrational entropy. AB - By treating DNA as a vibrating nonlinear lattice, an activated kinetic theory for DNA melting is developed to capture the breakage of the hydrogen bonds and subsequent softening of torsional and bending vibration modes. With a coarse grained lattice model, we identify a key bending mode with GHz frequency that replaces the hydrogen vibration modes as the dominant out-of-phase phonon vibration at the transition state. By associating its bending modulus to a universal in-phase bending vibration modulus at equilibrium, we can hence estimate the entropic change in the out-of-phase vibration from near-equilibrium all-atom simulations. This and estimates of torsional and bending entropy changes lead to the first predictive and sequence-dependent theory with good quantitative agreement with experimental data for the activation energy of melting of short DNA molecules without intermediate hairpin structures. PMID- 28987108 TI - Erratum: "Supramolecular structure fluctuations of an imidazolium-based protic ionic liquid" [J. Chem. Phys. 146, 134505 (2017)]. PMID- 28987109 TI - Non-conformal coarse-grained potentials for water. AB - Water is a notoriously difficult substance to model both accurately and efficiently. Here, we focus on descriptions with a single coarse-grained particle per molecule using the so-called approximate non-conformal and generalized Stockmayer potentials as the starting points. They are fitted using the radial distribution function and the liquid-gas density profile of the atomistic extended simple point charge (SPC/E) model by downhill simplex optimization. We compare the results with monatomic water (mW), ELBA, and direct iterative Boltzmann inversion of SPC/E. The results show that symmetrical potentials result in non-transferable models, that is, they need to be reparametrized for new state points. This indicates that transferability may require more complex models. Furthermore, the results also show that the addition of a point dipole is not sufficient to make the potentials accurate and transferable to different temperatures (300 K-500 K) and pressures without an appropriate choice of properties as targets during model optimization. PMID- 28987110 TI - Impact of ionic aggregate structure on ionomer mechanical properties from coarse grained molecular dynamics simulations. AB - Using coarse-grained molecular dynamics simulations, we study ionomers in equilibrium and under uniaxial tensile deformation. The spacing of ions along the chain is varied, allowing us to consider how different ionic aggregate morphologies, from percolated to discrete aggregates, impact the mechanical properties. From the equilibrium simulations, we calculate the stress-stress auto correlation function, showing a distinct deviation from the Rouse relaxation due to ionic associations that depends on ion content. We then quantify the morphology during strain, particularly the degree to which both chains and ionic aggregates tend to align. We also track the location of the ionomer peak in the anisotropic structure factor during strain. The length scale of aggregate order increases in the axial direction and decreases in the transverse direction, in qualitative agreement with prior experimental results. PMID- 28987111 TI - Decoupling of translational and rotational diffusion in quasi-2D colloidal fluids. AB - We observe the translational and rotational diffusion of dimer tracer particles in quasi-2D colloidal samples. The dimers are in dense samples of two different sizes of spherical colloidal particles, with the area fraction phi of the particles varying from dilute to nearly glassy. At low phi, rotational and translational diffusion have a ratio set by the dimer size, as expected. At higher phi, dimers become caged by their neighboring particles, and both rotational and translational diffusion become slow. For short dimers, we observe rapid reorientations so that the rotational diffusion is faster than the translational diffusion: the two modes of diffusion are decoupled and have different phi dependence. Longer dimers do not exhibit fast rotations, and we find that their translational and rotational diffusion stay coupled for all phi. Our results bridge prior results that used spheres (very fast rotation) and long ellipsoids (very slow rotation). PMID- 28987112 TI - Ionic liquids-mediated interactions between nanorods. AB - Surface forces mediated by room-temperature ionic liquids (RTILs) play an essential role in diverse applications including self-assembly, lubrication, and electrochemical energy storage. Therefore, their fundamental understanding is critical. Using molecular simulations, we study the interactions between two nanorods immersed in model RTILs at rod-rod separations where both structural and double layer forces are important. The interaction force between neutral rods oscillates as the two rods approach each other, similar to the classical structural forces. Such oscillatory force originates from the density oscillation of RTILs near each rod and is affected by the packing constraints imposed by the neighboring rods. The oscillation period and decay length of the oscillatory force are mainly dictated by the ion density distribution near isolated nanorods. When charges are introduced on the rods, the interaction force remains short range and oscillatory, similar to the interactions between planar walls mediated by some protic RTILs reported earlier. Nevertheless, introducing net charges to the rods greatly changes the rod-rod interactions, e.g., by delaying the appearance of the first force trough and increasing the oscillation period and decay length of the interaction force. The oscillation period and decay length of the oscillatory force and free energy are commensurate with those of the space charge density near an isolated, charged rod. The free energy of rod-rod interactions reaches local minima (maxima) at rod-rod separations when the space charges near the two rods interfere constructively (destructively). The insight on the short-range interactions between nanorods in RTILs helps guide the design of novel materials, e.g., ionic composites based on rigid-rod polyanions and RTILs. PMID- 28987113 TI - Influence of chirality on the thermal and electric properties of the columnar mesophase exhibited by homomeric dipeptides. AB - We present the first investigation of the influence of chirality on the thermal and electric properties in a biologically important homomeric dipeptide that exhibits a hexagonal columnar liquid crystal mesophase. The peptide employed has two chiral centres, and thus the two possible enantiopures are the (R,R) and (S,S) forms having opposite chirality. The measurements reported the span of the binary phase space between these two enantiopures. Any point in the binary diagram is identified by the enantiomeric excess Xee (the excess content of the R,R enantiopure over its S,S counterpart). We observe that the magnitude of Xee plays a pivotal role in governing the properties as evidenced by X-ray diffraction (XRD), electric polarization (Ps), dielectric relaxation spectroscopy (DRS) measurements, and the isotropic-columnar transition temperature. For example, XRD shows that while other features pointing to a hexagonal columnar phase remain the same, additional short-range ordering, indicating correlated discs within the column, is present for the enantiopures (Xee = +/-1) but not for the racemate (Xee = 0). Similarly, an electric-field driven switching whose profile suggests the phase structure to be antiferroelectric is seen over the entire binary space, but the magnitude is dependent on Xee; interestingly the polarization direction is axial, i.e., along the column axis. DRS studies display two dielectric modes over a limited temperature range and one mode (mode 2) connected with the antiferroelectric nature of the columnar structure covering the entire mesophase. The relaxation frequency and the thermal behaviour of mode 2 are strongly influenced by Xee. The most attractive effect of chirality is its influence on the polar order, a measure of which is the magnitude of the axial polarization. This result can be taken to be a direct evidence of the manifestation of molecular recognition and the delicate interplay between chiral perturbations and the magnitude of the polar order, a feature attractive from the viewpoint of devices based on, e.g., remnant polarization-a currently hot topic. To add further dimension to the work, the DRS measurements are also extended to elevated pressures. PMID- 28987114 TI - Exploring ultra-fast charge transfer and vibronic coupling with N 1s RIXS maps of an aromatic molecule coupled to a semiconductor. AB - We present for the first time two-dimensional resonant inelastic x-ray scattering (RIXS) maps of multilayer and monolayer bi-isonicotinic acid adsorbed on the rutile TiO2(110) single crystal surface. This enables the elastic channel to be followed over the lowest unoccupied molecular orbitals resonantly excited at the N 1s absorption edge. The data also reveal ultra-fast intramolecular vibronic coupling, particularly during excitation into the lowest unoccupied molecular orbital-derived resonance. Both elastic scattering and the vibronic coupling loss features are expected to contain the channel in which the originally excited electron is directly involved in the core-hole decay process. This allows RIXS data for a molecule coupled to a wide bandgap semiconductor to be considered in the same way as the core-hole clock implementation of resonant photoemission spectroscopy (RPES). However, contrary to RPES measurements, we find no evidence for the depletion of the participator channel under the conditions of ultra-fast charge transfer from the molecule to the substrate densities of states, on the time scale of the core-hole lifetime. These results suggest that the radiative core-hole decay processes in RIXS are not significantly modified by charge transfer on the femtosecond time scale in this system. PMID- 28987115 TI - On the use of nonrigid-molecular symmetry in nuclear motion computations employing a discrete variable representation: A case study of the bending energy levels of CH5. AB - A discrete-variable-representation-based symmetry adaptation algorithm is presented and implemented in the fourth-age quantum-chemical rotational vibrational code GENIUSH. The utility of the symmetry-adapted version of GENIUSH is demonstrated by the computation of seven-dimensional bend-only vibrational and rovibrational eigenstates of the highly fluxionally symmetric CH5+ molecular ion, a prototypical astructural system. While the numerical results obtained and the symmetry labels of the computed rovibrational states of CH5+ are of considerable utility by themselves, it must also be noted that the present study confirms that the nearly unconstrained motion of the five hydrogen atoms orbiting around the central carbon atom results in highly complex rotational-vibrational quantum dynamics and renders the understanding of the high-resolution spectra of CH5+ extremely challenging. PMID- 28987116 TI - Temperature dependence of band gaps and conformational disorder in PEDOT and its selenium and tellurium derivatives: Density functional calculations. AB - The conducting polymer poly(3,4-ethylenedioxythiophene), or PEDOT, is an attractive material for flexible electronics. We present combined molecular dynamics and quantum chemical calculations, based on density functional theory, of EDOT oligomers and isoelectronic selenium and tellurium derivatives (EDOS and EDOTe) to address the effect of temperature on the geometrical and electronic properties of these systems. With finite size scaling, we also extrapolate our results to the infinite polymers, i.e., PEDOT, PEDOS, and PEDOTe. Our computations indicate that the most favourable oligomer conformations at finite temperature are conformations around the flat trans-conformation and a non-flat conformation around 45 degrees from the cis-conformation. Also, the dihedral stiffness increases with the atomic number of the heteroatom. We find excellent agreement with experimentally measured gaps for PEDOT and PEDOS. For PEDOT, the gap does not increase with temperature, whereas this is the case for its derivatives. The conformational disorder and the choice of the basis set both significantly affect the calculated gaps. PMID- 28987117 TI - A kinetic Monte Carlo approach to study fluid transport in pore networks. AB - The mechanism of fluid migration in porous networks continues to attract great interest. Darcy's law (phenomenological continuum theory), which is often used to describe macroscopically fluid flow through a porous material, is thought to fail in nano-channels. Transport through heterogeneous and anisotropic systems, characterized by a broad distribution of pores, occurs via a contribution of different transport mechanisms, all of which need to be accounted for. The situation is likely more complicated when immiscible fluid mixtures are present. To generalize the study of fluid transport through a porous network, we developed a stochastic kinetic Monte Carlo (KMC) model. In our lattice model, the pore network is represented as a set of connected finite volumes (voxels), and transport is simulated as a random walk of molecules, which "hop" from voxel to voxel. We simulated fluid transport along an effectively 1D pore and we compared the results to those expected by solving analytically the diffusion equation. The KMC model was then implemented to quantify the transport of methane through hydrated micropores, in which case atomistic molecular dynamic simulation results were reproduced. The model was then used to study flow through pore networks, where it was able to quantify the effect of the pore length and the effect of the network's connectivity. The results are consistent with experiments but also provide additional physical insights. Extension of the model will be useful to better understand fluid transport in shale rocks. PMID- 28987118 TI - Protonated ions as systemic trapping agents for noble gases: From electronic structure to radiative association. AB - The deficiencies of argon, krypton, and xenon observed in the atmosphere of Titan as well as anticipated in some comets might be related to a scenario of sequestration by H3+ in the gas phase at the early evolution of the solar nebula. The chemical process implied is a radiative association, evaluated as rather efficient in the case of H3+, especially for krypton and xenon. This mechanism of chemical trapping might not be limited to H3+ only, considering that the protonated ions produced in the destruction of H3+ by its main competitors present in the primitive nebula, i.e., H2O, CO, and N2, might also give stable complexes with the noble gases. However the effective efficiency of such processes is still to be proven. Here, the reactivity of the noble gases Ar, Kr, and Xe, with all protonated ions issued from H2O, CO, and N2, expected to be present in the nebula with reasonably high abundances, has been studied with quantum simulation method dynamics included. All of them give stable complexes and the rate coefficients of their radiative associations range from 10-16 to 10 19 cm3 s-1, which is reasonable for such reactions and has to be compared to the rates of 10-16 to 10-18 cm3 s-1, obtained with H3+. We can consider this process as universal for all protonated ions which, if present in the primitive nebula as astrophysical models predict, should act as sequestration agents for all three noble gases with increasing efficiency from Ar to Xe. PMID- 28987119 TI - Investigation of the two- and three-fragment photodissociation of the tert-butyl peroxy radical at 248 nm. AB - The photodissociation dynamics of the tert-butyl peroxy (t-BuOO) radical are studied by fast-radical-beam coincidence translational spectroscopy. The neutral t-BuOO radical is formed by photodetachment of the corresponding t-BuOO- anion at 700 nm (1.77 eV), followed by dissociation at 248 nm (5.00 eV). Photofragment mass and translational energy distributions are obtained. The major channel is found to be three-body fragmentation to form O, CH3, and acetone (83%), with minor two-body fragmentation channels leading to the formation of O2 + tert-butyl radical (10%) and HO2 + isobutene (7%). Experimental results show that the translational energy distribution for two-body dissociation peaks is close to zero translational energy, with an isotropic angular distribution of fragments. These results indicate that two-body fragmentation proceeds via internal conversion to the ground electronic state followed by statistical dissociation. For three-body dissociation, the translational energy distribution peaks closer to the maximal allowed translational energy and shows an anisotropic distribution of the plane of the dissociating fragments, implying rapid dissociation on an excited-state surface. A small shoulder in the three-body translational energy distribution suggests that some three-fragment dissociation events proceed by a different mechanism, involving internal conversion to the ground electronic state followed by sequential dissociation. PMID- 28987120 TI - Energetic fluctuations in amorphous semiconducting polymers: Impact on charge carrier mobility. AB - We present a computational approach to model hole transport in an amorphous semiconducting fluorene-triphenylamine copolymer (TFB), which is based on the combination of molecular dynamics to predict the morphology of the oligomeric system and Kinetic Monte Carlo (KMC), parameterized with quantum chemistry calculations, to simulate hole transport. Carrying out a systematic comparison with available experimental results, we discuss the role that different transport parameters play in the KMC simulation and in particular the dynamic nature of positional and energetic disorder on the temperature and electric field dependence of charge mobility. It emerges that a semi-quantitative agreement with experiments is found only when the dynamic nature of the disorder is taken into account. This study establishes a clear link between microscopic quantities and macroscopic hole mobility for TFB and provides substantial evidence of the importance of incorporating fluctuations, at the molecular level, to obtain results that are in good agreement with temperature and electric field-dependent experimental mobilities. Our work makes a step forward towards the application of nanoscale theoretical schemes as a tool for predictive material screening. PMID- 28987121 TI - Bonding reactivity descriptor from conceptual density functional theory and its applications to elucidate bonding formation. AB - Condensed-to-atom Fukui functions which reflect the atomic reactivity like the tendency susceptible to either nucleophilic or electrophilic attack demonstrate the bonding trend of an atom in a molecule. Accordingly, Fukui functions based concepts, that is, bonding reactivity descriptors which reveal the bonding properties of molecules in the reaction were put forward and then applied to pericyclic and cluster reactions to confirm their effectiveness and reliability. In terms of the results from the bonding descriptors, a covalent bond can readily be predicted between two atoms with large Fukui functions (i.e., one governs nucleophilic attack while the other one governs electrophilic attack, or both of them govern radical attacks) for pericyclic reactions. For SinOm clusters' reactions, the clusters with a low O atom ratio readily form a bond between two Si atoms with big values of their Fukui functions in which they respectively govern nucleophilic and electrophilic attacks or both govern radical attacks. Also, our results from bonding descriptors show that Si-Si bonds can be formed via the radical mechanism between two Si atoms, and formations of Si-O and O-O bonds are possible when the O content is high. These results conform with experimental findings and can help experimentalists design appropriate clusters to synthesize Si nanowires with high yields. The approach established in this work could be generalized and applied to study reactivity properties for other systems. PMID- 28987122 TI - Extending pressure-matching to inhomogeneous systems via local-density potentials. AB - Bottom-up coarse-grained models describe the intermolecular structure of all-atom (AA) models with desirable accuracy and efficiency. Unfortunately, structure based models for liquids tend to dramatically overestimate the thermodynamic pressure and, consequently, tend to vaporize under ambient conditions. By employing a volume potential to introduce additional cohesion, self-consistent pressure-matching provides a simple and robust method for accurately reproducing the pressure equation of state (EoS) for homogeneous fluids, while still preserving an accurate description of intermolecular structure. Because they depend upon the global density, though, volume potentials cannot be directly employed for inhomogeneous systems, such as liquid-vapor interfaces. In the present work, we demonstrate that volume potentials can be readily adapted as potentials of the local density. The resulting local-density potentials provide an accurate description of the structure, pressure EoS, and local density fluctuations of an AA model for liquid methanol. Moreover, we demonstrate that very slight modifications to these local-density potentials allow for a quantitative description of either local or global density fluctuations. Most importantly, we demonstrate that the resulting potentials, which were parameterized to describe a homogeneous liquid, also generate stable liquid-vapor coexistence. However, further work is necessary to more accurately reproduce the interfacial density profile. PMID- 28987123 TI - Mixing of MnPc electronic states at the MnPc/Au(110) interface. AB - Manganese-phthalocyanines form assembled chains with a variety of ordered super structures, flat lying along the Au(110) reconstructed channels. The chains first give rise to a *5 symmetry reconstruction, while further deposition of MnPc leads to a *7 periodicity at the completion of the first single layer. A net polarization with the formation of an interface dipole is mainly due to the molecular pi-states located on the macrocycles pyrrole rings, while the central metal ion induces a reduction in the polarization, whose amount is related to the Mn-Au interaction. The adsorption-induced interface polarization is compared to other 3d-metal phthalocyanines, to unravel the role of the central metal atom configuration in the interaction process of the d-states. The MnPc adsorption on Au(110) induces the re-hybridization of the electronic states localized on the central metal atom, promoting a charge redistribution of the molecular orbitals of the MnPc molecules. The molecule-substrate interaction is controlled by a symmetry-determined mixing between the electronic states, involving also the molecular empty orbitals with d character hybridized with the nitrogen atoms of the pyrrole ring, as deduced by photoemission and X-ray absorption spectroscopy exploiting light polarization. The symmetry-determined mixing between the electronic states of the Mn metal center and of the Au substrate induces a density of states close to the Fermi level for the *5 phase. PMID- 28987124 TI - Improving the safety of breast implants: implant-associated lymphoma. PMID- 28987126 TI - Statistical and clinical significance. PMID- 28987127 TI - Corynebacterium minutissimum infection: erythrasma. PMID- 28987130 TI - A useful additional resource for FRACP candidates. PMID- 28987128 TI - Walking a mile in their shoes: reflections on being an international medical graduate. PMID- 28987131 TI - Less is more: chest pain pathways in clinical care. PMID- 28987132 TI - Improved Assessment of Chest pain Trial (IMPACT): assessing patients with possible acute coronary syndromes. AB - OBJECTIVE: To examine the safety and efficacy of the Improved Assessment of Chest pain Trial (IMPACT) protocol, a strategy for accelerated assessment of patients presenting to emergency departments (EDs) with chest pain. DESIGN, SETTING AND PARTICIPANTS: IMPACT was an intervention trial at a single tertiary referral hospital (Royal Brisbane and Women's Hospital) during February 2011 - March 2014. 1366 prospectively recruited patients presenting to the ED with symptoms of suspected acute coronary syndrome (ACS) were stratified into groups at low, intermediate or high risk of an ACS. INTERVENTION: High risk patients were treated according to NHFA/CSANZ guidelines. Low and intermediate risk patients underwent troponin testing (sensitive assay) 0 and 2 hours after presentation. Intermediate risk patients underwent objective testing after the second troponin test; low risk patients were discharged without further objective testing. MAIN OUTCOME MEASURES: The primary outcome was an ACS within 30 days of presentation. Secondary outcomes were ED and hospital lengths of stay (LOS). RESULTS: The IMPACT protocol stratified 244 (17.9%) patients to low risk, 789 (57.7%) to intermediate risk, and 333 (24.4%) to high risk categories. The overall 30-day ACS rate was 6.6%, but there were no ACS events in the low risk group, and 14 (1.8%) in the intermediate risk group. The median hospital LOS was 5.1 hours (IQR, 4.2-5.6 h) for low risk and 7.7 hours (IQR, 6.1-21 h) for intermediate risk patients. CONCLUSIONS: The IMPACT protocol safely and efficiently allowed a large proportion of patients presenting to EDs with chest pain to undergo accelerated assessment for risk of an ACS. CLINICAL TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12611000206921. PMID- 28987133 TI - Implementing change: evaluating the Accelerated Chest pain Risk Evaluation (ACRE) project. AB - OBJECTIVE: To evaluate hospital length of stay (LOS) and admission rates before and after implementation of an evidence-based, accelerated diagnostic protocol (ADP) for patients presenting to emergency departments (EDs) with chest pain. DESIGN: Quasi-experimental design, with interrupted time series analysis for the period October 2013 - November 2015. Setting, participants: Adults presenting with chest pain to EDs of 16 public hospitals in Queensland. INTERVENTION: Implementation of the ADP by structured clinical re-design. MAIN OUTCOME MEASURES: Primary outcome: hospital LOS. SECONDARY OUTCOMES: ED LOS, hospital admission rate, proportion of patients identified as being at low risk of an acute coronary syndrome (ACS). RESULTS: Outcomes were recorded for 30 769 patients presenting before and 23 699 presenting after implementation of the ADP. Following implementation, 21.3% of patients were identified by the ADP as being at low risk for an ACS. Following implementation of the ADP, mean hospital LOS fell from 57.7 to 47.3 hours (rate ratio [RR], 0.82; 95% CI, 0.74-0.91) and mean ED LOS for all patients presenting with chest pain fell from 292 to 256 minutes (RR, 0.80; 95% CI, 0.72-0.89). The hospital admission rate fell from 68.3% (95% CI, 59.3-78.5%) to 54.9% (95% CI, 44.7-67.6%; P < 0.01). The estimated release in financial capacity amounted to $2.3 million as the result of reduced ED LOS and $11.2 million through fewer hospital admissions. CONCLUSIONS: Implementing an evidence-based ADP for assessing patients with chest pain was feasible across a range of hospital types, and achieved a substantial release of health service capacity through reductions in hospital admissions and ED LOS. PMID- 28987134 TI - Testing for type 2 diabetes in Indigenous Australians: guideline recommendations and current practice. AB - OBJECTIVES: To determine the proportion of Aboriginal Controlled Community Health Service (ACCHS) patients tested according to three national diabetes testing guidelines; to investigate whether specific patient characteristics were associated with being tested. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional study of 20 978 adult Indigenous Australians not diagnosed with diabetes attending 18 ACCHSs across Australia. De-identified electronic whole service data for July 2010 - June 2013 were analysed. MAIN OUTCOMES MEASURES: Proportions of patients appropriately screened for diabetes according to three national guidelines for Indigenous Australians: National Health and Medical Research Council (at least once every 3 years for those aged 35 years or more); Royal Australian College of General Practitioners and Diabetes Australia (at least once every 3 years for those aged 18 years or more); National Aboriginal Community Controlled Health Organisation (annual testing of those aged 18 years or more at high risk of diabetes). RESULTS: 74% (95% CI, 74-75%) of Indigenous adults and 77% (95% CI, 76-78%) of 10 760 patients aged 35 or more had been tested for diabetes at least once in the past 3 years. The proportions of patients tested varied between services (range: all adults, 16-90%; people aged 35 years or more, 23-92%). 18% (95% CI, 18-19%) of patients aged 18 or more were tested for diabetes annually (range, 0.1-43%). Patients were less likely to be tested if they were under 50 years of age, were transient rather than current patients of the ACCHS, or attended the service less frequently. CONCLUSIONS: Some services achieved high rates of 3-yearly testing of Indigenous Australians for diabetes, but recommended rates of annual testing were rarely attained. ACCHSs may need assistance to achieve desirable levels of testing. PMID- 28987135 TI - Non-coeliac gluten or wheat sensitivity: emerging disease or misdiagnosis? AB - Non-coeliac gluten or wheat sensitivity (NCG/WS) is a condition characterised by adverse gastrointestinal and/or extra-intestinal symptoms associated with the ingestion of gluten- or wheat-containing foods, in the absence of coeliac disease or wheat allergy. Up to one in 100 people in Australia may have coeliac disease but many more report adverse gastrointestinal and/or extra-intestinal symptoms after eating wheat products. In the absence of validated biomarkers, a diagnosis of NCG/WS can only be made by a double-blind, placebo-controlled, dietary crossover challenge with gluten, which is difficult to apply in clinical practice. Of people self-reporting gluten or wheat sensitivity, only a small proportion (16%) will have reproducible symptoms after a blinded gluten challenge of gluten versus placebo in a crossover dietary trial and fulfil the current consensus criteria for a diagnosis of NCG/WS. A wide range of symptoms are associated with NCG/WS, including gastrointestinal, neurological, psychiatric, rheumatological and dermatological complaints. The pathogenesis of NCG/WS is not well understood, but the innate immune system has been implicated, and there is overlap with coeliac disease and the functional gastrointestinal disorders (irritable bowel syndrome and functional dyspepsia). Identification of NCG/WS is important as gluten-free diets carry risks, are socially restricting and are costlier than regular diets. PMID- 28987136 TI - Radiation therapy and early breast cancer: current controversies. AB - Radiation therapy (RT) is an important component of breast cancer treatment. RT reduces local recurrence and breast cancer mortality after breast conservation for all patients and for node-positive patients after a mastectomy. Short courses of RT over 3-4 weeks are generally as effective as longer courses. A patient subgroup where RT can be avoided after conservative surgery has not been consistently identified. A radiation boost reduces the risk of a recurrence in the breast but may be omitted for older patients with good prognosis tumours with clear margins. Axillary recurrences can take a long time to appear, with 35% occurring after 5 years. Leaving disease untreated in regional nodes is associated with reduced survival. Not all patients require radiation after neoadjuvant chemotherapy and a subsequent mastectomy. Modern RT equipment and techniques will further improve survival rates. PMID- 28987137 TI - A review of maturity onset diabetes of the young (MODY) and challenges in the management of glucokinase-MODY. PMID- 28987138 TI - A review of maturity onset diabetes of the young (MODY) and challenges in the management of glucokinase-MODY. PMID- 28987140 TI - Exit block in the intensive care unit. PMID- 28987139 TI - A stitch in time: stitching errors in digital radiology. PMID- 28987141 TI - A leader in acute stroke care. PMID- 28987142 TI - Around the universities and research institutes. PMID- 28987145 TI - In Conversation with the Dean of the FGDP(UK). PMID- 28987146 TI - Evolving Patterns of Oral Disease, Patient Needs and Expectations: Implications for Dental Care Provision. PMID- 28987144 TI - Cancer associated fibroblasts (CAFs) are activated in cutaneous basal cell carcinoma and in the peritumoural skin. AB - BACKGROUND: Cutaneous basal cell carcinoma (BCC) is the commonest cancer worldwide. BCC is locally invasive and the surrounding stromal microenvironment is pivotal for tumourigenesis. Cancer associated fibroblasts (CAFs) in the microenvironment are essential for tumour growth in a variety of neoplasms but their role in BCC is poorly understood. METHODS: Material included facial BCC and control skin from the peritumoural area and from the buttocks. With next generation sequencing (NGS) we compared mRNA expression between BCC and peritumoural skin. qRT-PCR, immunohistochemical and immunofluorescent staining were performed to validate the NGS results and to investigate CAF-related cyto and chemokines. RESULTS: NGS revealed upregulation of 65 genes in BCC coding for extracellular matrix components pointing at CAF-related matrix remodeling. qRT PCR showed increased mRNA expression of CAF markers FAP-alpha, PDGFR-beta and prolyl-4-hydroxylase in BCC. Peritumoural skin (but not buttock skin) also exhibited high expression of PDGFR-beta and prolyl-4-hydroxylase but not FAP alpha. We found a similar pattern for the CAF-associated chemokines CCL17, CCL18, CCL22, CCL25, CXCL12 and IL6 with high expression in BCC and peritumoural skin but absence in buttock skin. Immunofluorescence revealed correlation between FAP alpha and PDGFR-beta and CXCL12 and CCL17. CONCLUSION: Matrix remodeling is the most prominent molecular feature of BCC. CAFs are present within BCC stroma and associated with increased expression of chemokines involved in tumour progression and immunosuppression (CXCL12, CCL17). Fibroblasts from chronically sun-exposed skin near tumours show gene expression patterns resembling that of CAFs, indicating that stromal fibroblasts in cancer-free surgical BCC margins exhibit a tumour promoting phenotype. PMID- 28987147 TI - From Episodic Care to Life-long Maintenance of Oral Health. PMID- 28987148 TI - Changing Patient Behaviour: Past Successes, Future Challenges. PMID- 28987149 TI - New Frontiers in Dental Technology. PMID- 28987150 TI - Minimum Intervention (MI) Oral Healthcare Delivery Implementation - Overcoming the Hurdles. PMID- 28987151 TI - The Dentist of the Future: Dental Surgeon or Oral Physician? PMID- 28987152 TI - Current and Anticipated Developments in the Diagnosis and Management of Dental and Related Pain. PMID- 28987153 TI - Shaping the Dental Team of the Future. PMID- 28987154 TI - Developments in Dental Education and Training. PMID- 28987155 TI - The Business of Dentistry. PMID- 28987157 TI - Correction. PMID- 28987159 TI - Calling All Volunteers! PMID- 28987158 TI - Atrial Function as an Independent Predictor of Postoperative Atrial Fibrillation in Patients Undergoing Aortic Valve Surgery for Severe Aortic Stenosis. AB - BACKGROUND: Postoperative atrial fibrillation (POAF) is a common, clinically relevant, but hardly predictable complication after surgical aortic valve replacement. The aim of this study was to test the role of preoperative left atrial longitudinal strain as a predictor of POAF in clinical practice. METHODS: Sixty patients scheduled for aortic valve replacement for severe isolated aortic stenosis, in stable sinus rhythm, were prospectively enrolled and underwent full clinical, biochemical, and transthoracic echocardiographic assessment on the day before surgery. Left atrial strain-derived peak atrial longitudinal strain (PALS) and peak atrial contraction strain (PACS) were obtained. The occurrence of POAF was evaluated during the hospital stay after the intervention. RESULTS: POAF was present in 26 of 60 patients (43.3%). Among all clinical variables examined, age showed a significant correlation with POAF (P = .04), while no significant differences were noted regarding preoperative symptoms, cardiovascular risk factors, medications, and biochemical data. As for the echocardiographic parameters, only PALS and PACS showed strong, significant correlations with the occurrence of arrhythmia (P < .0001 on univariate analysis), with areas under the curve of 0.87 +/- 0.04 (95% CI, 0.76-0.94) for PALS and 0.85 +/- 0.05 (95% CI, 0.73-0.93) for PACS. In two comprehensive multivariate models, PALS and PACS remained significant predictors of POAF (odds ratio, 0.73 [95% CI, 0.61-0.88; P = .0008] and 0.72 [95% CI, 0.59-0.87; P = .0007]). No significant interaction was detected between PALS or PACS and other clinical and echocardiographic variables, including age, E/E' ratio, and left atrial enlargement. CONCLUSIONS: PALS and PACS indexes are routinely feasible and useful to predict POAF in patients with severe isolated aortic stenosis undergoing surgical aortic valve replacement. PMID- 28987161 TI - Intelligent Algorithms in Perioperative Echocardiography: A New Era. PMID- 28987160 TI - Giving Back, Mission Work. PMID- 28987162 TI - Neurotrauma. AB - Traumatic brain injury remains a major cause of morbidity and mortality throughout the world, affecting young and old alike. Pathologic data have been developed through observations of human autopsies and developing animal models to investigate mechanisms, although animal models do not represent the polypathology of human brain injury and there are likely to be significant differences in the anatomic basis of injury and cellular responses between species. Traumatic brain injury can be defined pathologically as either focal or diffuse, and can be considered to be either primary, directly related to the force associated with the neurotrauma, or secondary, developing as a downstream consequence of the neurotrauma. While neuropathology has traditionally focused on severe head injury, there is increasing recognition of the long-term consequences of traumatic brain injury, particularly repetitive mild traumatic brain injury, and a possible long-term association with chronic traumatic encephalopathy. PMID- 28987163 TI - Cellular reactions of the central nervous system. AB - Major cell types of the central nervous system comprise neurons, glial cells (astrocytes, oligodendrocytes, ependymal cells, and microglia), choroid plexus cells, cells related to blood vessels and coverings. These cells show a wide range of reactions to various noxious agents, which can be detected in routine stainings. Some of these reactions are nonspecific to different injuries; however some, such as the appearance of inclusion bodies, can be highly disease-specific. Immunohistochemical markers are widely used in neuropathologic diagnostic practice and help to understand the pathogenesis of diseases. The most widely used neuronal markers comprise phosphorylated and nonphosphorylated neurofilaments, microtubule-associated protein-2, NeuN, or synaptic markers such as synaptophysin. The best antibody for the detection of astrocytes is anti-GFAP (glial fibrillar acidic protein); however, to support a glial origin, S100 or vimentin is also used in the diagnostic practice. Further astroglial markers include connexin-43, excitatory amino acid transporters, aquaporin-4, heat shock protein Hsp27, and alpha-B-crystallin. Depending whether the tissue is fixed or nonfixed, different oligodendroglial markers are available, such as myelin basic protein, myelin oligodendrocyte glycoprotein, myelin-associated glycoprotein, proteolipid protein, Olig2, NG2, 2' 3'-cyclic nucleotide 3-phosphodiesterase (CNPase), and tubulin polymerization-promoting protein/p25 alpha (TPPP/p25). A wide range of microglia functions is recognized. Apart from a role in immune mediated disorders, inflammation, and response to injury, microglia are important during the development and aging of the brain. The best markers include the clone CR3/43, Iba1, and CD68. Evaluation of cell reactions is the first step in the diagnostic procedure. PMID- 28987164 TI - Neurometabolic and neurodegenerative diseases in children. AB - Neurometabolic and neurodegenerative diseases in children (NDDC) differ from those in adults in that most of the former are autosomal-recessively inherited - few have X-linked inheritance - while the latter are often sporadic or autosomal dominantly inherited. NDDC may be catabolic and/or anabolic conditions, some of which combine maldevelopmental and degenerative features, for instance, peroxisomal biogenesis disorders or congenital disorders of glycosylation. NDDC are often multiorgan disorders, such as lysosomal, peroxisomal, and polyglucosan disorders. This multiorgan involvement may be marked by extracerebral formation of disease-specific neuropathologic findings, especially in lysosomal diseases allowing diagnostic biopsies in easily accessible tissues, e.g., blood lymphocytes, skin, skeletal muscle, and rectum to be investigated by electron microscopy. NDDC comprise nonvacuolar and vacuolar lysosomal, peroxisomal, polyglucosan, amino and organic acid, white-matter disorders, and congenital disorders of glycosylation. PMID- 28987165 TI - Mitochondrial diseases. AB - Mitochondrial disorders represent a major challenge in medicine. Most of the mitochondrial proteins are encoded by the nuclear DNA (nDNA), whereas a very small fraction is encoded by the mitochondrial DNA (mtDNA). Mutations in mtDNA or mitochondria-related nDNA genes can result in mitochondrial dysfunction. The disease usually affects multiple organs in varying locations and severity; however, there are some forms which affect a single organ. The diagnosis of mitochondrial disorders is based on clinical examination, biochemical and histopathologic examinations, functional studies, and molecular genetic testing. Neuropathologic alterations of the muscle are variable and can range from striking abnormalities, such as cytochrome oxidase-negative and ragged red fibers, to nonspecific or minimal changes. Neuropathologic alterations in the brain show common features in disorders with different genetic background. These are characterized by various degrees of vacuolation in the white and gray matter, regional neurodegeneration with reactive astrogliosis, loss of oligodendrocytes, presence of macrophages and microgliosis, capillary proliferation, and mineralization of vessel walls. The advent of molecular genetics, the discovery of biomarkers and new sequencing platforms to perform targeted exome and whole genome sequencing have changed traditional approaches to diagnose mitochondrial diseases. PMID- 28987166 TI - Neurodegeneration with brain iron accumulation. AB - Neurodegeneration with brain iron accumulation (NBIA) describes a heterogeneous group of inherited rare clinical and genetic entities. Clinical core symptoms comprise a combination of early-onset dystonia, pyramidal and extrapyramidal signs with ataxia, cognitive decline, behavioral abnormalities, and retinal and axonal neuropathy variably accompanying these core features. Increased nonphysiologic, nonaging-associated brain iron, most pronounced in the basal ganglia, is often termed the unifying characteristic of these clinically variable disorders, though occurrence and extent can be fluctuating or even absent. Neuropathologically, NBIA disorders usually are associated with widespread axonal spheroids and local iron accumulation in the basal ganglia. Postmortem, Lewy body, TDP-43, or tau pathology has been observed. Genetics have fostered ongoing progress in elucidating underlying pathophysiologic mechanisms of NBIA disorders. Ten associated genes have been established, with many more being suggested as new technologies and data emerge. Clinically, certain symptom combinations can suggest a specific genetic defect. Genetic tests, combined with postmortem neuropathology, usually make for the final disease confirmation. Despite these advances, treatment to date remains mainly symptomatic. This chapter reviews the established genetic defects leading to different NBIA subtypes, highlights phenotypic presentations to direct genetic testing, and briefly discusses the scarce available treatment options and upcoming challenges and future hopes of the field. PMID- 28987167 TI - Nutritional and systemic metabolic disorders. AB - Vitamin deficiency disorders display a wide variety of neurologic signs and symptoms, the pathogenesis of which is not clearly understood. Metabolic encephalopathies (hepatic, hypoglycemic, and uremic) have to be considered in the differential diagnosis of patients with cognitive impairment, motor disturbances, psychiatric symptoms, seizures, and neuropathies. Calcifications (vascular wall and parenchymal) occur in the normal aging brain and in neurodegeneration; some associated genes are already described. PMID- 28987168 TI - Alcohol-related diseases. AB - Alcohol abuse and dependence are serious medical and economic problems in Western countries. Brain changes encountered in alcoholism are manifold and encompass brain atrophy, selective neuronal loss, astroglial, and microglial changes. Alcohol-related disorders are complex multifactorial disorders where the interaction of multiple genes and environment plays an important role in the pathogenesis. PMID- 28987169 TI - Neurotoxicology and drug-related disorders. AB - Neuropsychiatric disorders caused by toxic substances pose a great diagnostic challenge due to the large variety of changes caused in the central and peripheral nervous system. The pathogenetic mechanisms at work are multifaceted and partly not solved. In human drug abusers (cannabis, opiates, cocaine, amphetamines, methamphetamine and "designer drugs"), a broad spectrum of central nervous system alterations are observed including infarction, intracerebral and subarachnoidal hemorrhage, hypoxic-ischemic leukoencephalopathy, infections, neuronal loss, specific astroglial and microglial reaction patterns, and vascular changes, including the endothelial cell as well as the basal lamina. PMID- 28987170 TI - Neuropathology of epilepsy. AB - Epilepsy is one of the most common neurologic disorders, affecting about 50 million people worldwide. The disease is characterized by recurrent seizures, which are due to aberrant neuronal networks resulting in synchronous discharges. The term epilepsy encompasses a large spectrum of syndromes and diseases with different etiopathogenesis. The recent development of imaging and epilepsy surgery techniques is now enabling the identification of structural abnormalities that are part of the epileptic network, and the removal of these lesions may result in control of seizures. Access of this clinically well-characterized neurosurgical material has provided neuropathologists with the opportunity to study a variety of structural brain abnormalities associated with epilepsy, by combining traditional routine histopathologic methods with molecular genetics and functional analysis of the resected tissue. This approach has contributed greatly to a better diagnosis and classification of these structural lesions, and has provided important new insights into their pathogenesis and epileptogenesis. The present chapter provides a detailed description of the large spectrum of histopathologic findings encountered in epilepsy surgery patients, addressing in particular the nonneoplastic pathologies, including hippocampal sclerosis, malformations of cortical development, Sturge-Weber syndrome, and Rasmussen encephalitis, and reviews current knowledge regarding the underlying molecular pathomechanisms and cellular mechanisms mediating hyperexcitability. PMID- 28987171 TI - Acute and chronic bacterial infections and sarcoidosis. AB - Pathogen-induced inflammatory diseases mostly involving, but sometimes exclusively affecting, the central nervous system (CNS) manifest with a plethora of signs and symptoms. The different diseases are still difficult to cure despite modern diagnostic, preventive, and therapeutic advances, and this is mainly due to the host inflammatory response, leading to irreversible tissue damage. Knowledge about underlying pathomechanisms is constantly growing, and numerous studies on humans, human material, and animal models as well as in vitro systems have considerably increased our understanding of molecular mechanisms; however, there are still enormous uncertainties with respect to host-pathogen interaction and treatment. There are important regional variations as to prevalence and susceptibility of diseases, reflecting the importance of environmental factors, and immunogenetic peculiarities of different ethnicities. In addition, the opportunistic infections of the CNS are becoming very relevant, not only in the context of human immunodeficiency virus (HIV), but also in the context of modern, highly specific immunosuppressive or immunomodulatory treatments, evoking new and unmet diagnostic and therapeutic challenges. This chapter summarizes up-to-date knowledge about bacterial CNS infections, as well as cerebral sarcoidosis, focussing on morphologic aspects. PMID- 28987172 TI - Acute and chronic viral infections. AB - A large number of viruses belonging to various families are able to cause central nervous system (CNS) infections and contribute significantly to burden of disease in humans globally. Most viral CNS infections are benign and self-limiting, and most remain undiagnosed. However, some viruses can cause severe inflammation, leading to morbidity and mortality, and result in severe long-term residual damage and neurologic dysfunction in patients. The potential of viruses to cause CNS inflammation greatly varies depending on host factors, such as age, sex, and genetic background, as well as viral factors. Despite the need for protection against viral invasion and replication, the extent of the immune response in the CNS is carefully regulated to prevent excessive inflammation and tissue destruction leading to irretrievable loss of neurons. Direct cytopathology is for many virus infections a major cause of neurologic symptoms; however, the antiviral immune response can in some instances contribute substantially to pathology. This chapter highlights a selection of clinically important neurotropic viruses that infect the CNS and cause neurologic diseases such as meningitis, encephalitis, and myelitis in humans, with a focus on neuropathologic findings. PMID- 28987173 TI - Parasitic and fungal infections. AB - Parasitic infections of the central nervous system (CNS) comprise a plethora of infectious agents leading to a multitude of different disease courses and thus diagnostic and therapeutic challenges. The prevalence of different pathogens is basically dependent on geographic and ethnic backgrounds, its infectious route frequently involving a third party, such as flies or domestic animals. The present review focuses on cerebral malaria due to Plasmodium falciparum infection, and Toxoplasma gondii encephalitis. Fungi produce a large variety of inflammatory conditions of the CNS with a variegated spectrum of signs and symptoms, which may involve the meninges and the brain parenchyma, where they produce cerebritis or abscesses and granulomatous lesions, respectively. Fungal CNS lesions are increasingly prevalent and diagnostically relevant due to increasing numbers of human immunodeficiency virus-positive patients, increasing numbers of patients reaching old age suffering from malignant tumors or decreased immunity, and finally the increasing use of established and new immunosuppressive treatments, which increase the susceptibility of patients to develop invasive mycoses. Fungi appear with characteristic morphotypes comprising hyphae, yeasts, and pseudohyphae. The mode by which fungi penetrate into the CNS, and the host/immune requirements are incompletely understood and remain a challenge for research. PMID- 28987174 TI - Raised intracranial pressure and brain edema. AB - Acutely increased intracranial pressure (ICP) is a life-threatening neurosurgical emergency. Optimal management strategy is selected according to the causative process. Typical causes are intracranial bleeds like traumatic subdural, epidural, or intracerebral hematoma (ICH); spontaneous ICH, intraventricular hemorrhage, subarachnoid hemorrhage, and hydrocephalus. When occurring without significant brain injury and treated effectively before herniation, a full recovery can be expected. In intraparenchymal injuries a full recovery is unlikely since dead cells in the central nervous system leave an "empty hole," to be replaced by cerebrospinal fluid. The clinical recovery is based on the surviving cells that are able to make new synapses. Surgery may decrease ICP by removing significant mass effect. In all conditions, when notable injury of brain parenchyma occurs, brain edema may gradually increase ICP and further worsen the clinical condition. This is seen typically in large brain infarctions when the formation of brain edema may lead to increased ICP for hours and days. Brain edema is traditionally classified as vasogenic or cytotoxic but according to current knowledge is rather a continuum, starting with cytotoxic cell swelling followed by ionic edema and then vasogenic edema. Here we review the causes of increased ICP, including mechanisms of brain edema, with clinical examples. PMID- 28987175 TI - Inflammatory demyelinating diseases of the central nervous system. AB - Inflammatory demyelinating diseases are a heterogeneous group of disorders, which occur against the background of an acute or chronic inflammatory process. The pathologic hallmark of multiple sclerosis (MS) is the presence of focal demyelinated lesions with partial axonal preservation and reactive astrogliosis. Demyelinated plaques are present in the white as well as gray matter, such as the cerebral or cerebellar cortex and brainstem nuclei. Activity of the disease process is reflected by the presence of lesions with ongoing myelin destruction. Axonal and neuronal destruction in the lesions is a major substrate for permanent neurologic deficit in MS patients. The MS pathology is qualitatively similar in different disease stages, such as relapsing remitting MS or secondary or primary progressive MS, but the prevalence of different lesion types differs quantitatively. Acute MS and Balo's type of concentric sclerosis appear to be variants of classic MS. In contrast, neuromyelitis optica (NMO) and spectrum disorders (NMOSD) are inflammatory diseases with primary injury of astrocytes, mediated by aquaporin-4 antibodies. Finally, we discuss the histopathology of other inflammatory demyelinating diseases such as acute disseminated encephalomyelitis and myelin oligodendrocyte glycoprotein antibody-associated demyelination. Knowledge of the heterogenous immunopathology in demyelinating diseases is important, to understand the clinical presentation and disease course and to find the optimal treatment for an individual patient. PMID- 28987176 TI - Immune-mediated disorders. AB - Paraneoplastic and autoimmune encephalitis comprise a group of immune-mediated disorders that are associated with different immune effector mechanisms. Classic paraneoplastic neurologic syndromes are triggered by an antitumor immune response. The disease is considered to result from a T-cell response; in addition, patients harbour high titers of autoantibodies against intracellular antigens that are considered as epiphenomenon but are useful diagnostic markers. Neuropathology consists of T-cell-dominated inflammation, marked neuronal loss, and microglial activation with upregulation of HLA-DR. In the last decade, an increasing number of diseases associated with autoantibodies against neuronal surface antigens have been described. There is strong evidence that these autoantibodies are pathogenic and the associated syndromes are generally termed as antineuronal autoimmune encephalitis. Patients typically present with limbic, multifocal, or diffuse encephalitis and respond to immunotherapy. Neuropathologic descriptions are restricted to few biopsy and autopsy specimens and show mild inflammatory infiltrates and microglial activation, together with reduced expression of the respective target antigens, immunoglobulin deposits, and a variable degree of complement activation. Other putative autoimmune disorders of the central nervous system include, among others, Rasmussen encephalitis, chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS), acute cerebellitis, Susac syndrome, and Hashimoto encephalitis. While pathologic studies suggest an immune-mediated disease for Rasmussen encephalitis, CLIPPERS, acute cerebellitis, and Susac syndrome, neuropathologic descriptions of Hashimoto encephalitis are rare and the pathogenesis deserves further study. PMID- 28987177 TI - Techniques in neuropathology. AB - The primary objective for a neuropathologist is the characterization of the tissue that is being assessed and thus all available techniques ranging from naked-eye examination to assessment of genetic/epigenetic characteristics are currently applied. What is observed in the tissue obtained from a diseased subject is compared with what is observed in a healthy individual and, based on the outcome, neuropathologic definitions of diseases are constructed. Thus, with the naked eye a neuropathologist can confirm that a hemorrhage is observed in the brain, by histologic examination that the hemorrhage is caused by alterations in the brain vessels and, since 1954, applying Congo red dye neuropathologists have been able to state that congophilic angiopathy is detected. Since 1984, applying immunohistochemical methods neuropathologists have been able to verify that the protein seen in the vessel walls is beta-amyloid and by genetic/epigenetic analysis eventual mutation or modifications of genome might be detected. The development of new techniques is staggering and throughout this book the authors have listed techniques currently applied while assessing various disease-related hallmark lesions. In the following a general summary of techniques applied is given. PMID- 28987178 TI - Concepts and classification of neurodegenerative diseases. AB - Neurodegenerative diseases are disorders characterized by progressive loss of neurons associated with deposition of proteins showing altered physicochemical properties in the brain and in peripheral organs. Molecular classification of neurodegenerative disease is protein-based. This emphasizes the role of protein processing systems in the pathogenesis. The most frequent proteins involved in the pathogenesis of neurodegenerative diseases are amyloid-beta, prion protein, tau, alpha-synuclein, TAR-DNA-binding protein 43kDa, and fused-in sarcoma protein. There are further proteins associated mostly with hereditary disorders such as proteins encoded by genes linked to trinucleotide repeat disorders, neuroserpin, ferritin, and familial cerebral amyloidoses. The clinical presentations are defined by the distinct involvement of functional systems and do not necessarily indicate the molecular pathologic background. Seeding of pathologic proteins and hierarchic involvement of anatomic regions is commonly seen in neurodegenerative diseases. Overlap of neurodegenerative diseases and combinations of different disorders is frequent. Translation of neuropathologic categories of neurodegenerative diseases into in vivo detectable biomarkers is only partly achieved but intensive research is performed to reach this goal. PMID- 28987179 TI - Genetics of neurodegenerative diseases: an overview. AB - Genetic factors are central to the etiology of neurodegeneration, both as monogenic causes of heritable disease and as modifiers of susceptibility to complex, sporadic disorders. Over the last two decades, the identification of disease genes and risk loci has led to some of the greatest advances in medicine and invaluable insights into pathogenic mechanisms and disease pathways. Large scale research efforts, novel study designs, and advances in methodology are rapidly expanding our understanding of the genome and the genetic architecture of neurodegenerative disease. Here, we review major developments in the field to date, highlighting overarching historic trends and general insights. Monogenic neurodegenerative diseases are discussed from the perspectives of both rare Mendelian forms of common disorders, such as Alzheimer disease and Parkinson disease, and heterogeneous heritable conditions, including ataxias and spastic paraplegias. Next, we summarize the experiences from investigations of complex neurodegenerative disorders, including genomewide association studies. In the final section, we reflect upon the limitations of current findings and outline important future directions. Genetics plays an essential role in translational research, ultimately aiming to develop novel disease-modifying therapies for neurodegenerative disorders. We anticipate that individual genetic profiling will also be increasingly relevant in a clinical context, with implications for patient care in line with the proposed ideal of personalized medicine. PMID- 28987180 TI - Alzheimer disease. AB - Alzheimer disease neuropathology is characterized by the extracellular accumulation of Abeta peptide and intracellular aggregation of hyperphosphorylated tau. With the progression of the disease, macroscopic atrophy affects the entorhinal area and hippocampus, amygdala, and associative regions of the neocortex. The locus coeruleus is depigmented. The deposition of Abeta is first made of diffuse deposits. Amyloid focal deposits constitute the core of the senile plaque which also comprises a corona of tau-positive neurites. Abeta deposits are found successively in the neocortex, the hippocampus, the striatum, the mesencephalon, and finally the cerebellum together with the pontine nuclei (Thal phases). Tau pathology affects in a stereotyped order some specific nuclei of the brainstem, the entorhinal area, the hippocampus, and the neocortex - first the associative areas and secondarily the primary cortices (Braak stages). Loss of synapses is observed in association with tau and Abeta pathology; neuronal loss occurs in the most affected areas. Granulovacuolar degeneration and perisomatic granules are also linked to Alzheimer disease pathology. The physiopathology of Alzheimer disease remains unknown. Familial cases suggest that Abeta deposition is the initial step, but tau pathology appears early in the course and seems to be better correlated with the symptoms. PMID- 28987181 TI - Alpha-synucleinopathies. AB - A neurodegenerative disorder displaying an altered alpha-synuclein (alphaS) in the brain tissue is called alpha-synucleinopathy (alphaS-pathy) and incorporates clinical entities such as Parkinson disease (PD), PD with dementia, dementia with Lewy bodies, and multiple-system atrophy. Neuroradiologic techniques visualizing alphaS pathology in the brain or assays of alphaS in the cerebrospinal fluid or blood are probably available and will be implemented in the near future but currently the definite diagnosis of alphaS-pathy relies on a postmortem examination of the brain. Since the 1980s immunohistochemical technique based on the use of antibodies directed to proteins of interest has become a method of choice for neuropathologic diagnosis. Furthermore, since the 1990s it has been acknowledged that progressions of most neurodegenerative pathologies follow a certain predictable time-related neuroanatomic distribution. Currently, for Lewy body disease, two staging techniques are commonly used: McKeith and Braak staging. Thus, the neuropathologic diagnosis of a alphaS-pathy is based on detection of altered alphaS in the tissue and registration of the neuroanatomic distribution of this alteration in the brain. The clinicopathologic correlation is not absolute due to the quite frequent observation of incidental and concomitant alphaS pathology. PMID- 28987182 TI - Tauopathies. AB - Tauopathies are neurodegenerative disorders characterized by the deposition of abnormal tau protein in the brain. The spectrum of tau pathologies expands beyond the traditionally discussed disease forms like Pick disease, progressive supranuclear palsy, corticobasal degeneration, and argyrophilic grain disease. Emerging entities and pathologies include globular glial tauopathies, primary age related tauopathy, which includes neurofibrillary tangle dementia, chronic traumatic encephalopathy (CTE), and aging-related tau astrogliopathy. Clinical symptoms include frontotemporal dementia, corticobasal syndrome, Richardson syndrome, parkinsonism, pure akinesia with gait freezing and, rarely, motor neuron symptoms or cerebellar ataxia. Some disorders show specific neuroimaging features, while examination of the cerebrospinal fluid awaits markers for in vivo stratification of cases. The possibility of cell-to-cell propagation is a novel aspect of the pathogenesis of tauopathies, which is partly reflected by the hierarchic involvement of anatomic regions. This concept might have relevance for the development of therapies. For cost-effective screening for tau pathologies in neuropathologic practice, examination of the hippocampus, amygdala, and basal ganglia is recommended. Uncommon morphologies or unusually extensive forms of tau pathologies should raise the suspicion of a genetic background. Ongoing multidisciplinary studies are needed to understand the whole spectrum and significance of tau pathologies. PMID- 28987183 TI - Amyotrophic lateral sclerosis and non-tau frontotemporal lobar degeneration. AB - Amyotrophic lateral sclerosis (ALS) is the major motor neuron disorder. The hallmark features are progressive, irreversible motor neuron loss leading to denervation atrophy of muscles and death, usually within 5 years of disease onset. The hallmark proteins of the pathognomonic inclusions are SOD-1, TDP-43, or FUS; rarely the disease is caused by mutation of the respective genes. Frontotemporal lobar degeneration (FTLD) is genetically, neuropathologically, and clinically heterogeneous and may present as a dementia with three major clinical syndromes dominated by behavioral, language, and motor disorders, respectively. The characteristic aggregate-forming protein in non-tau FTLD is either TDP-43 or FUS. It has been known for several years that frontotemporal dementia (or less severe forms of cognitive impairment) may coexist with ALS. Recent discoveries in genetics (e.g., C9orf72 mutation) and the subsequent neuropathologic characterization have revealed remarkable overlap between ALS and non-tau FTLD also at a molecular level, indicating common molecular pathways in pathogenesis. After a historic overview we demonstrate and compare the macroscopic and microscopic appearances and molecular characteristics with emphasis on genetic background, neuroanatomic distribution, and morphology of abnormal protein aggregates and their possible association with specific mutations. The clinicopathologic classifications and correlations are also discussed. PMID- 28987184 TI - Trinucleotide repeat disorders. AB - Trinucleotide repeat disorders comprise a variable group of inherited neurodegenerative diseases, with a large range in prevalence figures. There is a broad range in clinical presentations, but many of these diseases lead to some form of ataxia or other movement disorders, which are frequently combined with cognitive or psychiatric disturbances. This group can be divided into CAG- versus non-CAG-repeat diseases. Apart from spinocerebellar ataxia type 6 and 12 (SCA6 and SCA12), these CAG-repeat diseases, as well as Huntington disease-like 2 (HDL2) and SCA8, can be neuropathologically identified using 1C2 polyglutamine antibodies. In fragile X-associated tremor and ataxia, SCA6 and SCA12 ubiquitin/p62-positive and 1C2-negative inclusion bodies can be observed. In the other diseases proteinaceous inclusions are not found. For definite diagnosis genetic analysis is necessary. PMID- 28987185 TI - Cerebrospinal fluid circulation and hydrocephalus. AB - Hydrocephalus (HC) is classically defined as dynamic imbalance between the production and absorption of cerebrospinal fluid (CSF) leading to enlarged ventricles. Potential causative factors include various brain disorders like tumors causing obstruction of CSF flow within the ventricular system or the subarachnoid space. Classification of HC is based on the site of CSF flow obstruction guiding optimal treatment, with endoscopic third ventriculostomy in intraventricular obstruction and CSF shunt in communicating HC. Another clinically relevant classification is acute and chronic; the most frequent chronic form is idiopathic normal-pressure hydrocephalus (iNPH). The reported incidence of HC varies according to the study population and classification used. The incidence of congenital HC is approximately 0.4-0.6/1,000 newborns and the annual incidence of iNPH varies from 0.5/100,000 to 5.5/100,000. Radiologically, ventricular dilatation may be nonspecific, and differentiation of iNPH from other neurodegenerative diseases may be ambiguous. There are no known specific microscopic findings of HC but a systematic neuropathologic examination is needed to detect comorbid diseases and possible etiologic factors of HC. Depending on the etiology of HC, there are several nonspecific signs potentially to be seen. PMID- 28987186 TI - Prion diseases. AB - The human prion diseases comprise Creutzfeldt-Jakob disease, variably protease sensitive prionopathy, Gerstmann-Straussler-Scheinker disease, fatal familial insomnia, and kuru. Each is a uniformly fatal rare neurodegenerative disease in which conformational changes in the prion protein are thought to be the central pathophysiologic event. The majority of cases of human prion diseases occur worldwide in the form of sporadic Creutzfeldt-Jakob disease and a minority of around 10-15% are associated with mutations of the prion protein gene, termed PRNP, in the forms of genetic Creutzfeldt-Jakob disease, Gerstmann-Straussler Scheinker disease, and fatal familial insomnia. Prion diseases are also transmissible and occur in iatrogenic and zoonotic forms (iatrogenic Creutzfeldt Jakob disease and variant Creutzfeldt-Jakob disease respectively), adding a public health dimension to their management. Despite having a high public profile, human prion diseases are both rare and heterogeneous in their clinicopathologic phenotype, sometimes making a diagnosis challenging. A combined clinical, genetic, neuropathologic, and biochemical approach to diagnosis is therefore essential. The intensive study of these diseases continues to inform on neurodegenerative mechanisms and the role of protein misfolding in more common neurodegenerative diseases such as Parkinson disease and Alzheimer disease. PMID- 28987187 TI - Spinal cord. AB - We first present a brief historic review of developments in the understanding of spinal cord clinical neuroanatomy and neurophysiology over the past 200 years. We then discuss the technical aspects that apply to the examination of the human spinal cord giving details on the interrelations between the spinal cord and the overlying structures, including the meninges and vertebrae. The subsequent discussion focuses on diseases of the spinal cord. Diseases that affect the spinal cord are vascular disease, diseases of spinal column, trauma, developmental abnormalities, central nervous system degenerative disease, inflammatory disease, metabolic and nutritional myelopathies, and tumors. We summarize our knowledge regarding general reactions of spinal cord tissue to disease, in particular Wallerian degeneration of descending/ascending tracts and axonal reaction. Two categories of disease will be covered in depth: vascular disease of the spinal cord, including a review of normal vascular anatomy, and diseases of the vertebral column that can affect the cord secondarily. PMID- 28987188 TI - Diseases of the skeletal muscle. AB - After the advances created by the use of cryostat sections and histochemistry 60 years ago, muscle histopathology is now living a real renaissance. In the field of genetic neuromuscular disorders, muscle biopsy analysis is fundamental to address questions about pathogenicity and protein expression when new genes are discovered through next-generation sequencing approaches. Moreover, the identification of the same gene mutated in previously considered distinct histopathologic entities imposes a constant reassessment of morphologic boundaries in several groups of disorders. In other fields like the acquired inflammatory myopathies, histologic analysis nowadays helps to affirm a diagnosis, set up therapeutic strategies, and verify the success of immunosuppressive treatment. In this exciting scenario morphologists are definitely key figures in the neuromuscular field. The objective of this chapter is to give an overview on morphology of the most frequent and recently identified muscle conditions, stressing the importance that only a combined analysis of clinical findings, muscle histology, and specific ancillary investigations is effective in reaching a precise diagnosis and orienting therapy. PMID- 28987189 TI - Diseases of the peripheral nerves. AB - This chapter reviews the diseases of the peripheral nerves from a neuropathologic point of view, with a special focus on specific morphologic changes, and includes a summary of the histopathologic methods available for their diagnosis. As the rate of obesity and the prevalence of type 2 diabetes increase, diabetic neuropathy is the most common cause of peripheral neuropathy. Many systemic disorders with metabolic origin, like amyloidosis, hepatic failure, vitamin deficiencies, uremia, lipid metabolism disorders, and others, can also cause axonal or myelin alterations in the peripheral nervous system. The most notable causes of toxic neuropathies are chemotherapeutic agents, alcohol consumption, and exposure to heavy metals and other environmental or biologic toxins. Inflammatory neuropathies cover infectious neuropathies (Lyme disease, human immunodeficiency virus, leprosy, hepatitis) and neuropathies of autoimmune origin (sarcoidosis, Guillain-Barre syndrome/acute inflammatory demyelinating polyneuropathy, chronic inflammatory demyelinating polyneuropathy, and diverse forms of vasculitis. The increasing number of known diseases causing gene mutations in hereditary peripheral neuropathies requires precise characterization, which includes histopathology. PMID- 28987190 TI - Clinical neuropathology of brain tumors. AB - Brain tumor typing is a major task in the daily practice of clinical neuropathologists. For more than 100 years, brain tumors have been classified on the basis of a histogenetic concept, with the definition of more than 120 brain tumor entities over time. In the past decades, biomedical research on brain tumors has led to the identification of clinically meaningful diagnostic, prognostic, and predictive molecular markers. Taking this progress into account, the 2016 update of the World Health Organization classification of tumors of the central nervous system has incorporated for the first time molecular markers for definition of brain tumor entities. This development has resulted in integrated diagnostics on the basis of histologic and molecular characteristics. This chapter summarizes essential features of brain tumors in the light of integrated diagnostics. To provide a comprehensive view on the individual tumor entities, we included crucial epidemiologic, clinical, and neuroradiologic aspects as well. In addition we illustrate neuroimaging and histologic characteristics of the various tumor types. In this way we aim to provide concise up-to-date insight into the nature and classification of brain tumors. PMID- 28987191 TI - Developmental and perinatal brain diseases. AB - This chapter briefly describes the normal development of the nervous system, the neuropathology and pathophysiology of acquired and secondary disorders affecting the embryo, fetus, and child. They include CNS manifestations of chromosomal change; forebrain patterning defects; disorders of the brain size; cell migration and specification disorders; cerebellum, hindbrain and spinal patterning defects; hydrocephalus; secondary malformations and destructive pathologies; vascular malformations; arachnoid cysts and infectious diseases. The distinction between malformations and disruptions is important for pathogenesis and genetic counseling. PMID- 28987192 TI - Bioimaging and surgery of brain tumors. AB - Bioimaging of brain tumors using nuclear medicine techniques complements computed tomography (CT) and magnetic resonance imaging (MRI), thus allowing more accurate diagnosis in clinically ambiguous situations. Special tracers for positron emission tomography (PET) have been developed which allow monitoring and planning of therapy. PET data may provide also presurgical evidence with regard to the presence of clinically relevant molecular brain tumor biomarkers. Combined PET/CT and PET/MR hybrid imaging systems will further enhance bioimaging-based brain tumor analysis. The main aim of brain tumor surgery is maximal safe tumor resection with preservation of neurologic functions, and to relieve tumor-related symptoms. In deep-seated unresectable tumors, diagnostic biopsy may be the main surgical goal. Special pre- and intraoperative techniques and approaches, including multidisciplinary team approaches, have been developed to optimize these surgical goals. Differences in spectrum, biology, and clinical presentation of brain tumors in the pediatric patient population demand special surgical expertise to warrant optimal postoperative patient outcome. PMID- 28987193 TI - Brain tumors - other treatment modalities. AB - Management of tumors of the central nervous system is challenging for clinicians for various reasons, including complex diagnostic procedures, limited penetration of drugs into brain tissue, and the prerequisite to preserve brain function in any case of therapeutic intervention. Therapeutic success is dependent on the efforts, skills, and cooperation of involved specialists and disciplines. Knowledge and ability to apply adequate therapeutic modalities in an interdisciplinary approach in due time are crucial, necessitating coordination of diagnostic procedures and therapeutic interventions by means of multidisciplinary brain tumor boards. In this chapter we present in brief the essential current standards and future perspectives for therapy modalities that complement surgery of brain tumors. PMID- 28987194 TI - Overview of cerebrospinal fluid cytology. AB - Cerebrospinal fluid (CSF) cytology, i.e., the cytologic evaluation of its cellular composition, forms an integral part of the neurologist's armamentarium. Total and differential cell counts provide important first information across a spectrum of pathologic conditions involving the central nervous system and its coverings. CSF samples require immediate processing, ideally within 1 hour from collection. Upon centrifugation cytology is commonly assessed on May-Grunwald Giemsa stains. Several additional stains are available for the identification of infectious agents such as bacteria or fungi, or the further specification of neoplastic cells by immunocytochemistry. The evaluation warrants familiarity with cytologic characteristics of cells across normal and diseased states. In normal CSF, lymphocytes and monocytes are encountered. A predominance of neutrophil granulocytes suggests bacterial meningitis and prompts search for intracellular bacteria. In contrast, in viral and chronic infections lymphocytes and monocytes prevail. Upon activation lymphocytes typically enlarge and eventually differentiate into plasma cells. Similarly, monocytes differentiate into macrophages that clear cellular debris. Macrophages that contain fragments of erythrocytes or hemoglobin degradation products are referred to as erythro- or siderophages, both of which indicate prior subarachnoid hemorrhage. Likewise, the detection of tumor cells is specific for neoplastic meningitis, although false negative CSF cytologies are frequent. In summary, detailed morphologic workup of CSF samples provides valuable diagnostic information and is mandated in all cases with elevated cell count, computed tomography-negative suspected subarachnoid hemorrhage, and neoplastic meningitis. In all cases it needs to be interpreted in the clinical context and complements other clinical and laboratory findings. PMID- 28987195 TI - Comorbidities. AB - The term comorbidities or mixed pathologies is used when brain tissue, a surgical sample, or postmortem brain displays a mixture of protein alterations or other pathologies. Most of the alterations when seen in sufficient extent are considered causative, are related to a certain clinical phenotype, i.e., when hyperphosphorylated tau (HPtau) is observed in occipital cortex concomitant with beta-amyloid (Abeta), the diagnosis is Alzheimer disease (AD). When HPtau is observed in hippocampal structures in a subject with extensive and widespread alpha-synuclein pathology, a Lewy body disease (LBD), the HPtau pathology is considered as a concomitant alteration. There are numerous reports indicating that when "concomitant" pathologies are seen in a subject with certain neurodegenerative diseases, the clinical phenotype might be altered. In addition there are those cases where many alterations are seen in a sparse extent, but jointly they lead to a clinical syndrome. Thus today it is not sufficient to confirm a certain pathology to be seen, i.e., AD- or LBD-related; in addition the concomitant aging-related alterations have to be looked for. PMID- 28987196 TI - Overview of neuroradiology. AB - Neuroradiology with computed tomography (CT) and magnetic resonance imaging (MRI) is essential for the initial evaluation of patients with a clinical suspicion of brain and spine disorders. Morphologic imaging is required to obtain a probable diagnosis to support the treatment decisions in pre- and perinatal disorders, vascular diseases, traumatic injuries, metabolic disorders, epilepsy, infection/inflammation, neurodegenerative disorders, degenerative spinal disease, and tumors of the central nervous system. Different postprocessing tools are increasingly used for three-dimensional visualization and quantification of lesions. Additional information is provided by angiographic methods and physiologic CT and MRI techniques, such as diffusion MRI, perfusion CT/MRI, MR spectroscopy, functional MRI, tractography, and nuclear medicine imaging methods. Positron emission tomography (PET) is now integrated with CT (PET/CT), and PET/MR scanners have recently also been introduced. These hybrid techniques facilitate the co-registration of lesions with different modalities, and give new possibilites for functional imaging. Repeated imaging is increasingly performed for treatment monitoring. The improved imaging techniques together with the neuropathologic diagnosis after biopsy or surgery allow more personalized treatment of the patient. Neuroradiology also includes endovascular treatment of aneurysms and arteriovenous malformations as well as thrombectomy in acute stroke. This catheter-based treatment has replaced invasive neurosurgery in many cases. PMID- 28987197 TI - Neuropathology of cerebrovascular diseases. AB - The chapter describes the epidemiology of cerebrovascular diseases, anatomy of the cerebral blood vessels, pathophysiology of ischemia, hypoxia, hypoxemia, anemic hypoxia, histotoxic hypoxia, carbon monoxide damage, hyperoxid brain damage and decompression sickness, and selective cell and regional vulnerability; diseases of the blood vessels including atherosclerosis, hypertensive angiopathy, small vessel disease, inflammatory vascular diseases, cerebral amyloid angiopathies, CADASIL, CARASIL and other diseases that can lead to cerebrovascular occlusion; intracranial and intraspinal aneurysms and vascular malformations; hematologic disorders that can cause cerebral infarct or hemorrhage; brain ischemic damage; and spontaneous intracranial bleeding. Within ischemic brain damage, focal cerebral ischemia, hemorrhagic infarct, brain edema, penumbra, global cerebral ischemia, venous thrombosis, lacunas and lacunar state, status cribosus, granular atrophy of the cerebral cortex, hippocampal sclerosis, vascular leukoencephalopathy Binswanger type and multi-infarct encephalopathy are discussed in detail. Cognitive impairment of vascular origin deserves an individual section. PMID- 28987198 TI - Banking brain tissue for research. AB - Well-characterized human brain tissue is crucial for scientific breakthroughs in research of the human brain and brain diseases. However, the collection, characterization, management, and accessibility of brain human tissue are rather complex. Well-characterized human brain tissue is often provided from private, sometimes small, brain tissue collections by (neuro)pathologic experts. However, to meet the increasing demand for human brain tissue from the scientific community, many professional brain-banking activities aiming at both neurologic and psychiatric diseases as well as healthy controls are currently being initiated worldwide. Professional biobanks are open-access and in many cases run donor programs. They are therefore costly and need effective business plans to guarantee long-term sustainability. Here we discuss the ethical, legal, managerial, and financial aspects of professional brain banks. PMID- 28987199 TI - Preface. PMID- 28987200 TI - Foreword. PMID- 28987202 TI - Getting Serious About School. PMID- 28987201 TI - Children's Division Chair Update. PMID- 28987204 TI - A Comment on Cullen K "From Squires Quest! II: A Serious Video Game Intervention": Methodological Issues. PMID- 28987205 TI - Response to A Comment on Cullen K "From Squires Quest! II: A Serious Video Game Intervention": Methodological Issues. PMID- 28987203 TI - Informing Intervention Strategies to Reduce Energy Drink Consumption in Young People: Findings From Qualitative Research. AB - OBJECTIVE: To determine young people's knowledge of energy drinks (EDs), factors influencing ED consumption, and intervention strategies to decrease ED consumption in young people. DESIGN: Eight group interviews with young people (aged 12-25 years). SETTING: Community groups and secondary schools in Perth, Western Australia. PARTICIPANTS: Forty-one young people, 41% of whom were male and 73% of whom consumed EDs. PHENOMENON OF INTEREST: Factors influencing ED consumption and intervention strategies informed by young people to reduce ED consumption. ANALYSIS: Two researchers conducted a qualitative content analysis on the data using NVivo software. RESULTS: Facilitators of ED consumption included enhanced energy, pleasant taste, low cost, peer pressure, easy availability, and ED promotions. Barriers included negative health effects, unpleasant taste, high cost, and parents' disapproval. Strategies to reduce ED consumption included ED restrictions, changing ED packaging, increasing ED prices, reducing visibility in retail outlets, and research and education. CONCLUSION AND IMPLICATIONS: Because many countries allow the sale of EDs to people aged <18 years, identifying ways to minimize potential harm from EDs is critical. This study provided unique insights into intervention strategies suggested by young people to reduce ED consumption. In addition to more research and education, these strategies included policy changes targeting ED sales, packaging, price, and visibility. Future research might examine the feasibility of implementing such interventions. PMID- 28987206 TI - Beware of Predators. PMID- 28987207 TI - Keeping Cool When Things Heat Up During a Malignant Hyperthermia Crisis. AB - This article describes the experience of a health care team at a maternity center during their care for a woman exhibiting an atypical presentation of malignant hyperthermia and outlines the steps taken to rapidly identify the condition and begin treatment to save her life. Key components in ensuring a positive outcome in a malignant hyperthermia crisis include increased awareness and readiness to effectively treat and reverse the signs and symptoms of this condition. PMID- 28987208 TI - A Literature Review of Alternative Therapies for Postpartum Depression. AB - Postpartum depression is a debilitating disorder that requires greater awareness and treatment. Depending on severity of symptoms, standard treatment calls for individual psychotherapy and medication. Although postpartum depression can lead to negative health outcomes for women and their offspring, numerous barriers prevent women from receiving appropriate care. A review of the literature shows that nontraditional modes of psychotherapy dominate recent studies, whereas data for other complementary options are severely lacking. Further research is needed to help identify cost-effective alternative therapies for treating postpartum depression. Combined with prevention and screening, treatment options that suit women's varied situations and preferences must be explored to increase reception and adherence to treatment and, ultimately, to improve outcomes. PMID- 28987209 TI - Does the Coping Assessment for Laboring Moms (CALM) Scale Enhance Perception of Nursing Presence? AB - Traditional 0-to-10 pain assessment may be inadequate during labor. The Coping Assessment for Laboring Moms (CALM) scale was developed to focus on facial, behavioral, psychosocial, vocalization, and verbal expressions to aid holistic nursing support during childbirth. Using a comparative design, the 0-to-10 pain and CALM scales were evaluated to determine differences in women's perceptions of nursing presence using the Positive Presence Index during labor at a community hospital in the Pacific Northwest. Positive Presence Index scores for knowing what would work best for me, comforting touch, taking care of everything so I could concentrate, and understanding what I was saying were significantly higher among women when nurses used the CALM tool to guide labor support. The CALM scale needs further testing with a larger, more diverse population. PMID- 28987210 TI - Application of Kotter's Theory of Change to Achieve Baby-Friendly Designation. AB - Creating an environment that optimally supports exclusive breastfeeding can require a cultural transformation. Our initial attempt at obtaining Baby-Friendly Hospital Initiative (BFHI) designation was unsuccessful when surveyors determined insufficient enculturation of BFHI practices. Using Kotter's theory of change, we overcame the barriers, enhanced our practices, and effectively transformed the culture, and our facility ultimately became the first maternity hospital in Pennsylvania to obtain BFHI designation. Nursing leadership was essential to this process. Our experience serves as a template for others seeking to achieve Healthy People 2020 goals related to breastfeeding. PMID- 28987211 TI - Oocyte Cryopreservation for Fertility Preservation in Healthy Women. AB - Advancements in methods of fertility preservation have resulted in more options available to women seeking to postpone reproduction. Preservation of unfertilized oocytes provides women with the possibility for reproduction even after age related declines in fertility might make conceiving a child difficult to impossible. As oocyte cryopreservation rises in popularity among women, it is crucial for nurses and other clinicians to understand the background, process, ethical issues, and risks involved to help women make informed medical decisions. PMID- 28987212 TI - Depression Among Arab American and Arab Immigrant Women in the United States. AB - The difficult and tense political climate Arab populations are currently facing may be exacerbating mental health issues, reducing forms of social support in friend circles, and decreasing the desire to seek health care. There is room to better understand the mental health needs of Arab women residing in the United States and to develop policies and interventions that keep these women safe and in care. This column reviews two recent studies; the first examines barriers to reporting intimate partner violence and depression among Arab American women and the second highlights stressors and social support for Arab women immigrants throughout their immigration experience. PMID- 28987213 TI - Update on the Essure System for Permanent Birth Control. AB - In 2002, the U.S. Food and Drug Administration approved the Essure system for permanent birth control. Implantation with this device offers a minimally invasive option for permanent female contraception that is placed during a brief office visit. Unlike laparoscopic tubal sterilization, the Essure procedure requires no hospitalization or general anesthesia, resulting in minimal recovery time. After a decade of stability in the report of adverse effects, the U.S. Food and Drug Administration noted a sharp increase in patient-reported adverse events, including chronic pelvic pain, irregular bleeding, allergic reactions, and autoimmune-like reactions. In response to this increase in complaints, the U.S. Food and Drug Administration issued updated guidelines for patient education and counseling. This article discusses those updates, as well as implications for nurses who provide health care to women seeking permanent contraception. PMID- 28987214 TI - Tobacco Use and Women's Health. PMID- 28987215 TI - Breast Cancer Screening. PMID- 28987216 TI - Under Her Wing. PMID- 28987217 TI - Preface: Special Issue on Algal Biorefinery. PMID- 28987218 TI - Cover Story: Zebrafish as a screening tool for the systemic circulation of nanoparticles. PMID- 28987219 TI - Role of viral infections in the development and exacerbation of asthma in children. AB - Viral infections are closely linked to wheezing illnesses in children of all ages. Respiratory syncytial virus (RSV) is the main causative agent of bronchiolitis, whereas rhinovirus (RV) is most commonly detected in wheezing children thereafter. Severe respiratory illness induced by either of these viruses is associated with subsequent development of asthma, and the risk is greatest for young children who wheeze with RV infections. Whether viral illnesses actually cause asthma is the subject of intense debate. RSV-induced wheezing illnesses during infancy influence respiratory health for years. There is definitive evidence that RSV-induced bronchiolitis can damage the airways to promote airway obstruction and recurrent wheezing. RV likely causes less structural damage and yet is a significant contributor to wheezing illnesses in young children and in the context of asthma. For both viruses, interactions between viral virulence factors, personal risk factors (eg, genetics), and environmental exposures (eg, airway microbiome) promote more severe wheezing illnesses and the risk for progression to asthma. In addition, allergy and asthma are major risk factors for more frequent and severe RV-related illnesses. Treatments that inhibit inflammation have efficacy for RV-induced wheezing, whereas the anti-RSV mAb palivizumab decreases the risk of severe RSV-induced illness and subsequent recurrent wheeze. Developing a greater understanding of personal and environmental factors that promote more severe viral illnesses might lead to new strategies for the prevention of viral wheezing illnesses and perhaps reduce the subsequent risk for asthma. PMID- 28987222 TI - Controversies in Dentoalveolar and Preprosthetic Surgery. AB - Dentoalveolar surgeries are among the more common procedures performed by oral maxillofacial surgeons. It is only natural that there are several controversies associated with many aspects of this type of surgery. Although good scientific evidence is the basis of most oral maxillofacial procedures, some of what is accepted as common wisdom may not meet strict guidelines of evidence-based practice. This article explores some controversies that are relevant to the current practice of dentoalveolar surgery. PMID- 28987220 TI - Viral infections in allergy and immunology: How allergic inflammation influences viral infections and illness. AB - Viral respiratory tract infections are associated with asthma inception in early life and asthma exacerbations in older children and adults. Although how viruses influence asthma inception is poorly understood, much research has focused on the host response to respiratory viruses and how viruses can promote; or how the host response is affected by subsequent allergen sensitization and exposure. This review focuses on the innate interferon-mediated host response to respiratory viruses and discusses and summarizes the available evidence that this response is impaired or suboptimal. In addition, the ability of respiratory viruses to act in a synergistic or additive manner with TH2 pathways will be discussed. In this review we argue that these 2 outcomes are likely linked and discuss the available evidence that shows reciprocal negative regulation between innate interferons and TH2 mediators. With the renewed interest in anti-TH2 biologics, we propose a rationale for why they are particularly successful in controlling asthma exacerbations and suggest ways in which future clinical studies could be used to find direct evidence for this hypothesis. PMID- 28987223 TI - Controversies in Maxillofacial Trauma. AB - Craniomaxillofacial trauma management has continued to improve and evolve as a result of advances in technology and scientific inquiry. Controversies exist where there is little evidence-based literature to guide treatment in frontal sinus management, rigid versus absorbable fixation, open versus closed treatment of mandibular condyle fractures, extraction of teeth in the line of fracture, optimal timing for repair of mandible fractures, antibiotic use for facial wounds and fractures, and reconstructive materials in orbital fracture reconstruction. This article reviews current literature to resolve some of the controversies, to improve patient care by reducing variability and uncertainty in the optimal management of facial trauma patients. PMID- 28987224 TI - Controversies in Traditional Oral and Maxillofacial Reconstruction. AB - Traditional reconstruction of the head and neck and significantly evolved over the last 20 to 30 years with advances in microvascular surgery, biologic materials such as bone morphogenic protein, and dental implant predictability. Earlier and more definitive reconstruction can now be achieved with combining therapies, allowing patients immediate restoration of function and improved cosmetics. Antiresorptive medications, such as Denosumab and bisphosphonates, have complicated bony reconstruction treatments with altered biology and less predictable results. Virtual surgical planning is a major advancement for reconstruction pretreatment planning and designing of intraoperative tools to expedite the operation and achieve more predictable results. PMID- 28987225 TI - Controversies in Microvascular Maxillofacial Reconstruction. AB - The effectiveness and reliability of microvascular reconstruction for large defects in the head and neck is no longer disputed. However, many controversies still persist in the ideal perioperative management of patients undergoing free tissue transfer. The optimal method of postoperative monitoring, the use of vasoconstrictors in the perioperative period, and the use of anticoagulants in the postoperative period remain topics of debate. This article offers recommendations on each of these controversies based on a review of the current literature. PMID- 28987226 TI - Controversies in Orthognathic Surgery. AB - Controversy has accompanied orthognathic surgery since its adaptation for the correction of dentofacial deformities. With the development of less invasive and less morbid osteotomy designs, questions regarding overall osteotomy stability have abounded. The transition from prolonged intermaxillary fixation and wire osteosynthesis to rigid internal fixation has spurred questions regarding the most effective fixation technique, and challenged previously accepted hierarchies of stability. These questions represent only the surface of a sea of debate and discussion, as measures have been taken to optimize patient outcome, minimize patient morbidity, and maximize operating room productivity. PMID- 28987227 TI - Controversies in Facial Cosmetic Surgery. AB - Facial cosmetic surgery techniques are constantly updated to meet the expectations of patients who demand less invasive procedures and less recovery time. Current trends in lower eyelid surgery call for periorbital fat repositioning instead of excision of fat. Controversies still exist in chin augmentations regarding osseous genioplasty versus alloplastic chin implant. The benefits, disadvantages, and considerations of these procedures are discussed. PMID- 28987228 TI - Current Controversies in Metopic Suture Craniosynostosis. AB - Metopic craniosynostosis is being reported with an increasing incidence and is now the second most common type of isolated suture craniosynostosis. Numerous areas of controversy exist in the work-up and management, including defining the diagnosis in the less severe phenotype, the association with neurodevelopmental delay, the impact of surgical treatment, and the applicability of various techniques and their timing on outcomes. PMID- 28987229 TI - Controversies in Oral and Maxillofacial Oncology. AB - Imaging studies are essential components of tumor diagnosis, staging, assessing tumor response to neoadjuvant and adjuvant therapies, and postoperative surveillance on completion of definitive treatment. Treatment of early stage clinically node negative oral cavity squamous cell carcinoma is controversial. Approximately 3% of all head and neck tumors arise within the parotid gland and most often within the superficial lobe, lateral to the facial nerve; about 80% are benign and most are pleomorphic adenoma. In patients with dry eyes failing multiple other treatment modalities and facing ongoing pain and loss of vision, microvascular transplant of the submandibular gland is a viable option. PMID- 28987230 TI - Controversies in Obstructive Sleep Apnea Surgery. AB - Obstructive sleep apnea (OSA) is a common chronic disease characterized by repetitive pharyngeal collapse during sleep. OSA is associated with cardiovascular disease and increased mortality, among other issues. Continuous positive airway pressure (CPAP) is considered first line therapy for OSA, but is not always tolerated. Both non-surgical and surgical alternative management strategies are available for the CPAP intolerant patient. This article explores controversies surrounding airway evaluation, definition of successful treatment, and surgical management of the CPAP intolerant patient with moderate to severe OSA. Controversies specific to maxillomandibular advancement (MMA) are also discussed. PMID- 28987231 TI - Controversies in Anesthesia for Oral and Maxillofacial Surgery. AB - The future of office-based anesthesia for oral and maxillofacial surgery is at risk. Oral and maxillofacial surgeons have been on the forefront of providing safe and effective outpatient anesthesia for decades. Recent changes in Medicare policies have had, and will continue to have, a significant effect on the training of oral and maxillofacial surgery residents regarding anesthesia. The outcome of these changes can have a major effect on the specialty of oral and maxillofacial surgery and a cornerstone of the profession. PMID- 28987232 TI - Controversies in Implant Surgery. AB - Dental implants are a mainstream treatment protocol to replace missing teeth. Patient and clinician demands have led to shorter length and narrower diameter implants, immediately placed implants into infected sites, and the use of implants in children. This article reviews some of the controversial topics in implant dentistry, and presents the evidence that supports and challenges these newer techniques. Because long-term studies are often not available, especially for implants in infected sites, mini implants, and implants in the growing patient, the field continues to evolve. PMID- 28987233 TI - Controversies in Oral and Maxillofacial Surgery. PMID- 28987234 TI - Ending the Spanking Debate. PMID- 28987235 TI - Effects of l-arginine supplementation associated with continuous or interval aerobic training on chronic heart failure rats. AB - OBJECTIVE: Chronic heart failure (CHF) is related with exercise intolerance and impaired nitric oxide (NO) production, which can lead to several functional capacity alterations. Considering the possible superiority of aerobic interval training compared to continuous training and the capacity of l-arginine to restore the NO pathway, the aim of the present study was to investigate whether these treatments are beneficial to exercise capacity, muscle mass preservation and hemodynamic, inflammatory and oxidative stress parameters in CHF rats. METHODS: Thirty-eight male Wistar rats post 6weeks of myocardial infarction (MI) surgery were randomly assigned into 6 CHF groups: sedentary (SED, n=6); SED+Arg (n=7); ACT (n=8); ACT+Arg (n=5); AIT (n=7); AIT+Arg (n=5). Exercise test capacity (ETC) was performed pre and post 8weeks of intervention. Supplemented rats received Arg (1g/kg) by oral gavage (7*/week). Exercise training was performed on a rat treadmill (5*/week). Hemodynamic variables, tissue collection, congestion, inflammatory cytokines, and oxidative parameters were evaluated at the end of protocols. RESULTS: All trained groups showed a superior exercise capacity compared to SED groups on the post-intervention test (p<0.0001). Pulmonary congestion was attenuated in AIT and AIT+Arg compared with the SED group (p<0.05). Left ventricular end-diastolic pressure (LVEDP) was lower in ACT+Arg, AIT, and AIT+Arg groups than SED group (p<0.05). Association of AIT with Arg supplementation was able to improve hemodynamic responses (left ventricular systolic pressure (LVSP), systolic blood pressure (SBP), +dP/dtmax, and -dP/dtmax (p<0.05), likewise, decrease muscular and renal lipid peroxidation and tumor necrosis factor (TNF)-alpha, and increase interleukin (IL)-10/TNF-alpha plasmatic levels (p<0.01). Groups that associated aerobic exercise with Arg supplementation (ACT+Arg and AIT+Arg) revealed higher gastrocnemius mass compared to the SED group (p<0.01). CONCLUSIONS: Both aerobic training protocols were capable to improve aerobic capacity, and the association with Arg supplementation was important to attenuate muscle loss. Moreover, interval training associated with Arg supplementation elicits greater improvements in hemodynamic parameters, contributing to reduction in pulmonary congestion, and demonstrated particular responses in the inflammatory profile and in the antioxidant status. PMID- 28987236 TI - Associations of cord blood metabolites with perinatal characteristics, newborn anthropometry, and cord blood hormones in project viva. AB - CONTEXT: Metabolomics has emerged as a powerful tool to characterize biomarkers and elucidate physiological processes underlying adverse health outcomes. Little is known of these relationships during gestation and infancy, which are critical period for development of metabolic disease risk. OBJECTIVES: To identify cord blood metabolite patterns associated with birth size; and to investigate relations of the birth size-associated metabolite patterns, and a branched chain amino acid (BCAA) metabolite pattern with a range of newborn and perinatal characteristics. METHODS: Using untargeted mass-spectrometry, we quantified metabolites in cord blood of 126 mother-child pairs. After excluding 103 xenobiotics, we used principal components analysis (PCA) to consolidate the remaining 606 metabolites into principal components ("factors"). Next, we identified factors associated with gestational age-and sex-standardized birthweight z-score (BW/GA) and examined associations of the BW/GA-associated pattern(s) and the BCAA pattern with cord blood insulin, leptin, adiponectin, insulin-like growth factor (IGF)-1, IGF-2, and IGF binding protein 3 (IGFBP-3) using multivariable linear regression. Finally, we examined associations of maternal/perinatal characteristics with the cord blood metabolite patterns. RESULTS: Mean BW/GA z-score was 0.27+/-0.98 units. About half of the infants were male (52.4%) and white (57.1%). Of the 6 factors identified from PCA, one was associated with higher BW/GA: Factor 5, which comprised metabolites involved in energy production (malate, succinate, fumarate) and nucleotide turnover (inosine 5-monophosphate, adenosine 5-monophosphate, cytidine 5-monophosphate) pathways. In multivariable analysis, Factor 5 was related to higher cord blood leptin (1.64 [95% CI: 0.42, 2.87] ng/mL) and IGF-1 even after adjusting for IGFBP-3 (3.35 [0.25, 6.44] ng/mL). The BCAA pattern was associated with higher BW/GA (0.20 [0.03, 0.36] z-scores) and IGFBP-3 (106.5 [44.7, 168.2] ng/mL). No maternal characteristics were associated with either metabolite pattern; however, infants born via Cesarean delivery exhibited a higher score for Factor 5, and gestation length was inversely associated with the BCAA pattern. CONCLUSIONS: Metabolites in energy production and DNA/RNA turnover pathways in cord blood are associated with larger size at birth, and higher leptin and IGF-1. Similarly, the BCAA pattern was associated with larger birth size and IGFBP-3. PMID- 28987237 TI - Effect of home-based exercise intervention on fasting insulin and Adipocytokines in colorectal cancer survivors: a randomized controlled trial. AB - BACKGROUND AND AIMS: Elevated circulating insulin is associated with increased risk of recurrence and cancer mortality in early-stage colorectal cancer (CRC). We conducted a randomized controlled trial to determine the effect of a 12-week home-based exercise program on fasting insulin, adipocytokines, and physical function in CRC survivors. METHODS: One hundred and twenty-three stage II-III CRC patients were randomly assigned to either a home-based exercise (n=62) or standard care control group (n=61) for 12weeks. Home-based exercise consisted of aerobic and resistance training, with a goal of obtaining >=18 metabolic equivalent task (MET)-h/wk. Participants in the exercise group were instructed to participate in >18MET-h/wk. of aerobic and resistance exercise while the participants in the control group were asked to maintain their usual daily activity. The primary outcome was fasting insulin levels. Secondary outcomes were adiponectin, TNF-alpha levels and 6min walk distance from baseline to post intervention. RESULTS: After the 12-weeks, moderate-vigorous physical activity participation increased from 9.1+/-14.7MET-h/wk. to 26.6+/-21.7MET-h/wk. in the exercise group, with no change in the control group (p<0.01 for group and time interaction). Circulating insulin level decreased by 1MUU/ml (6.0+/-3.9 vs. 5.0+/ 3.5, p=0.009) in the exercise group with no change in the control group (p=0.022 for group and time interaction). A similar trend was observed in TNF-alpha (p=0.030 for group and time interaction). Six minute walk distance increased by 25.2m in the exercise group with no change in the control group (p=0.061 for group and time interaction). CONCLUSIONS: The 12week home-based exercise program increased level of physical activity and decreased circulating insulin levels in CRC survivors. PMID- 28987239 TI - Dipeptidyl peptidase 4 inhibitor attenuates obesity-induced myocardial fibrosis by inhibiting transforming growth factor-betal and Smad2/3 pathways in high-fat diet-induced obesity rat model. AB - Obesity-induced myocardial fibrosis may lead to diastolic dysfunction and ultimately heart failure. Activation of the transforming growth factor (TGF) betal and its downstream Smad2/3 pathways may play a pivotal role in the pathogenesis of obesity-induced myocardial fibrosis, and the antidiabetic dipeptidyl peptidase 4 inhibitors (DPP4i) might affect these pathways. We investigated whether DPP4i reduces myocardial fibrosis by inhibiting the TGF beta1 and Smad2/3 pathways in the myocardium of a diet-induced obesity (DIO) rat model. Eight-week-old male spontaneously hypertensive rats (SHRs) were fed either a normal fat diet (chow) or a high-fat diet (HFD) and then the HFD-fed SHRs were randomized to either the DPP4i (MK-0626) or control (distilled water) groups for 12weeks. At 20weeks old, all the rats underwent hemodynamic and metabolic studies and Doppler echocardiography. Compared with the normal fat diet (chow)-fed SHRs, the HFD-fed SHRs developed a more intense degree of hyperglycemia and dyslipidemia and showed a constellation of left ventricular (LV) diastolic dysfunction, and exacerbated myocardial fibrosis, as well as activation of the TGF-beta1 and Smad2/3 pathways. DPP4i significantly improved the metabolic and hemodynamic parameters. The echocardiogram showed that DPP4i improved the LV diastolic dysfunction (early to late ventricular filling velocity [E/A] ratio, 1.49+/-0.21 vs. 1.77+/-0.09, p<0.05). Furthermore, DPP4i significantly reduced myocardial fibrosis and collagen production by the myocardium and suppressed TGF beta1 and phosphorylation of Smad2/3 in the heart. In addition, DPP4i decreased TGF-beta1-induced collagen production and TGF-beta1-mediated phosphorylation and nuclear translocation of Smad2/3 in rat cardiac fibroblasts. In conclusion, DPP4 inhibition attenuated myocardial fibrosis and improved LV diastolic dysfunction in a DIO rat model by modulating the TGF-beta1 and Smad2/3 pathways. PMID- 28987238 TI - Thyroid stimulating hormone exhibits the impact on LDLR/LDL-c via up-regulating hepatic PCSK9 expression. AB - CONTEXT: Thyroid stimulating hormone (TSH) has received increasing attention as being closely associated with increased low-density lipoprotein cholesterol (LDL c) level and higher atherosclerotic risks. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is known for increasing circulating LDL-c level by inducing LDL receptor degradation. However, whether TSH influences hepatic PCSK9 expression and LDL-c metabolism remains unclear. METHODS: First, the correlation between TSH and lipid profiles were investigated in euthyroid population and in subclinical hypothyroidism patients. Then, an in vitro study was conducted to validate the effects of TSH on hepatic PCSK9 expression in HepG2 cells. RESULTS: Serum TSH concentrations positively correlated with LDL-c levels in euthyroid subjects. Subclinical hypothyroidism patients with higher serum TSH levels showed significantly increased serum PCSK9 levels than the matched euthyroid participants (151.29 (89.51-293.03) vs. 84.70 (34.98-141.72) ng/ml, P<0.001), along with increased LDL-c concentrations. In HepG2 cells, LDLR expression on the plasma membrane was decreased, and PCSK9 mRNA and protein levels were synchronously upregulated after recombinant human TSH (rhTSH) treatment, while the effects could be blocked by TSH receptor blocking antibody K1-70. Sterol regulatory element binding protein (SREBP) 1c and SREBP2 mRNA expressions were enhanced after rhTSH treatment, and specific siRNAs significantly inhibited the effects of rhTSH. Furthermore, there was a noticeable induction of PCSK9 expression by rhTSH even though HMGCR gene expression was silenced. CONCLUSION: We conclude a regulating role of TSH on hepatic PCSK9 expression, which further contributing to a higher LDL-c level. PMID- 28987241 TI - Editors Note Focusing on Violence in the African American Community. PMID- 28987240 TI - Protein tyrosine phosphatase 1B deficiency in podocytes mitigates hyperglycemia induced renal injury. AB - OBJECTIVE: Diabetic nephropathy is one of the most devastating complications of diabetes, and growing evidence implicates podocyte dysfunction in disease pathogenesis. The objective of this study was to investigate the contribution of protein tyrosine phosphatase 1B (PTP1B) in podocytes to hyperglycemia-induced renal injury. METHODS: To determine the in vivo function of PTP1B in podocytes we generated mice with podocyte-specific PTP1B disruption (hereafter termed pod PTP1B KO). Kidney functions were determined in control and pod-PTP1B KO mice under normoglycemia and high-fat diet (HFD)- and streptozotocin (STZ)-induced hyperglycemia. RESULTS: PTP1B expression increased in murine kidneys following HFD and STZ challenges. Under normoglycemia control and pod-PTP1B KO mice exhibited comparable renal functions. However, podocyte PTP1B disruption attenuated hyperglycemia-induced albuminuria and renal injury and preserved glucose control. Also, podocyte PTP1B disruption was accompanied with improved renal insulin signaling and enhanced autophagy with decreased inflammation and fibrosis. Moreover, the beneficial effects of podocyte PTP1B disruption in vivo were recapitulated in E11 murine podocytes with lentiviral-mediated PTP1B knockdown. Reconstitution of PTP1B in knockdown podocytes reversed the enhanced insulin signaling and autophagy suggesting that they were likely a consequence of PTP1B deficiency. Further, pharmacological attenuation of autophagy in PTP1B knockdown podocytes mitigated the protective effects of PTP1B deficiency. CONCLUSIONS: These findings demonstrate that podocyte PTP1B deficiency attenuates hyperglycemia-induced renal damage and suggest that PTP1B may present a therapeutic target in renal injury. PMID- 28987243 TI - 2017 Presidential Installation Speech. PMID- 28987242 TI - Culture, Communication, and DSM-5 Diagnostic Reliability. PMID- 28987244 TI - Implicit Bias in Pediatric Academic Medicine. AB - OBJECTIVE: Despite known benefits of diversity, certain racial/ethnic groups remain underrepresented in academic pediatrics. Little research exists regarding unconscious racial attitudes among pediatric faculty responsible for decisions on workforce recruitment and retention in academia. This study sought to describe levels of unconscious racial bias and perceived barriers to minority recruitment and retention among academic pediatric faculty leaders. METHODS: Authors measured unconscious racial bias in a sample of pediatric faculty attending diversity workshops conducted at local and national meetings in 2015. A paper version of the validated Implicit Association Test (IAT) measured unconscious racial bias. Subjects also reported perceptions about minority recruitment and retention. RESULTS: Of 68 eligible subjects approached, 58 (85%) consented and completed the survey with IAT. Of participants, 83% had leadership roles and 93% were involved in recruitment. Participants had slight pro-white/anti-black bias on the IAT (M = 0.28, SD = 0.49). There were similar IAT scores among participants in leadership roles (M = 0.33, SD = 0.47) and involved in recruitment (M = 0.28, SD = 0.43). Results did not differ when comparing participants in local workshops to the national workshop (n = 36, M = 0.29, SD = 0.40 and n = 22, M = 0.27, SD = 0.49 respectively; p = 0.88). Perceived barriers to minority recruitment and retention included lack of minority mentors, poor recruitment efforts, and lack of qualified candidates. CONCLUSIONS: Unconscious pro-white/anti-black racial bias was identified in this sample of academic pediatric faculty and leaders. Further research is needed to examine how unconscious bias impacts decisions in academic pediatric workforce recruitment. Addressing unconscious bias and perceived barriers to minority recruitment and retention represent opportunities to improve diversity efforts. PMID- 28987245 TI - The Effect of Relaxation on Mother's Anxiety and Maternal-Fetal Attachment in Primiparous IVF Mothers. AB - OBJECTIVES: Infertility is one of the main stressful events of life and a crisis affecting various dimensions of infertile couples' lives. Relaxation, as a strategy, can be effective in the individuals' resistance to stress and anxiety. Therefore, the present study aimed to assess the effect of relaxation on mother's anxiety and maternal-fetal attachment in primiparous women who used In Vitro Fertilization (IVF) to get pregnant. METHODS: In this clinical trial, 80 primiparous women who had used IVF to get pregnant were randomly divided into a control and an intervention group. The intervention group took part in four 90 min relaxation classes in addition to receiving the routine pregnancy care. Anxiety and maternal-fetal attachment were evaluated before and one month after the intervention. Also, maternal-infantile attachment score was computed after delivery. The statistical analyses were performed using the SPSS statistical software. Chi-square and independent t-test was used to analyze the data. RESULTS: The results revealed no significant difference between the two groups regarding the mean scores of anxiety and attachment before the intervention. However, a significant difference was observed in this regard after the intervention (41.4 +/- 4.1 vs. 51.0 +/- 10.4, P < 0.01). CONCLUSION: The study results showed that relaxation training was effective in reduction of anxiety and increase of maternal-fetal attachment in the women who had used IVF to get pregnant. Although there are other methods for reducing anxiety, relaxing can be used for IVF women due to its ease of use and its wide acceptance. PMID- 28987247 TI - Impact of Autologous Stem Cell Transplantation on Blood Pressure and Renal Function in Multiple Myeloma Patients. AB - BACKGROUND: Autologous stem cell transplantation (ASCT) reverses kidney failure in one-third of multiple myeloma (MM) patients, which may lead to blood pressure (BP) improvement. We evaluate the long term impact of ASCT on BP and renal function in MM patients. METHODS: We studied 192 MM patients that underwent ASCT. We compared BP readings and glomerular filtration rate (GFR) at 4 weeks before ASCT, on day of ASCT and post-ASCT at 30, 100 and 180 days. RESULTS: Mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) on day of ASCT and at both 30 and 100 days post-ASCT was significantly lower as compared to pre ASCT SBP and DBP. There was a significantly higher mean GFR at day of ASCT and 30 days post-ASCT and significantly lower mean GFR at 180 days post-ASCT as compared to pre-ASCT. White patients had similar patterns to the total group for SBP, DBP, and GFR except for SBP which was still significantly lower and GFR which was not significantly different at 180 days. African-American patients showed no significant reductions in the mean values of SBP and DBP and no significant increases for GFR in follow-up after day of ASCT. Furthermore, the mean value of GFR was significantly lower at 180 days post-ASCT. CONCLUSIONS: ASCT in MM patients had a positive impact on SBP and DBP and GFR but the impact was minimal for African-American patients. We recommend that clinicians consider closer follow-up of BP and kidney function and more intense therapy in African-Americans with MM. PMID- 28987246 TI - Influence of Prevalent and Incident Atrial Fibrillation on Post-Trial Major Events in ALLHAT. AB - AIMS: Limited information is available on long-term antihypertensive and lipid lowering therapy effects on hypertensive patients with atrial fibrillation/flutter (AF/AFL) compared to those without. AF/AFL at baseline or during the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) (mean follow-up 4.9 years) markedly increased risk of stroke, heart failure, CHD, and all-cause mortality. We aimed to determine if AF/AFL continued to impact outcomes during post-trial follow-up (mean 3.8 years). METHODS: Patients were randomized to chlorthalidone, amlodipine, or lisinopril, and to pravastatin vs. usual care in the lipid-lowering trial (LLT). Of 31,473 available subjects, AF/AFL occurred in 854; 383/14,371 chlorthalidone (2.7%), 247/8565 amlodipine (2.9%), and 224/8537 lisinopril (2.6%). Post-hoc analyses utilized administrative databases for post-trial data. Individuals with AF/AFL were compared to those without during post-trial. Outcomes were analyzed by treatment groups for the antihypertensive and LLT trials. RESULTS: Among 854 AF/AFL participants, 491 (57.5%) died: 220 in-trial, 271 post-trial. Ten-year all cause mortality rates for those with in-trial AF/AFL were similar for chlorthalidone and lisinopril, but lower for amlodipine (68, 66, and 49 per 100 persons, respectively); adjusted HR for amlodipine vs. chlorthalidone was 0.68 (95% CI, 0.54-0.87). Ten-year all-cause mortality rates were 57 vs. 65 per 100 persons (pravastatin vs. usual care); non-CVD mortality rates, 18 vs. 39 per 100 persons (pravastatin vs. usual care) (adjusted HR = 0.46, 95% CI, 0.24-0.86). CONCLUSION: Post-trial follow-up revealed continued deleterious AF/AFL effects. The amlodipine (ALLHAT) and pravastatin (ALLHAT-LLT) treatment groups showed lower all-cause and non-CVD mortality compared to the chlorthalidone and usual care groups, respectively. PMID- 28987248 TI - The Effect of MIpaste Plus and Reminpro on Incipient Caries Using DIAGNOdent and SEM: An Invitro Study. AB - BACKGROUND: The remineralization of early caries lesion has an effective role on decreasing caries. For initial remineralization of caries lesion, using Compounds of Casein phosphopeptides (CPP) in different studies has been proposed. REMINPRO including Fluoride, Xylitol and Calcium phosphate has just been offered in the market. This study aims to investigate the efficacy of Reminpro and MI paste plus in terms of remineralization of early enamel lesions. MATERIALS AND METHODS: In 15 samples of healthy enamels of the maxillary first premolar teeth and 15 samples of Primary Mandibular First Molar under the effect of demineralized gel, artificial caries has been created. The samples have been divided in 3 groups of 20. After performing the cycles of demineralization and remineralization during 5 weeks, the samples were investigated by DIAGNOdent and two samples from each group were compared with SEM. To investigate the remineralization of enamel, two way ANOVA and to compare the groups in pair, the post hoc tests were used. RESULTS: The mean of mineralization of teeth in the group using reminpro was 25.2 +/- 6.16 and in the group using MI paste plus was 23 +/- 5.60, which was significantly high. CONCLUSIONS: MI paste plus in mineralization of initial enamel caries were more efficient that reminpro pate. PMID- 28987249 TI - Significance of Serum Uric Acid in Pregnancy Induced Hypertension. AB - BACKGROUND AND OBJECTIVE: Hypertension is one of the common medical complications of pregnancy and contributes significantly to maternal and perinatal morbidity and mortality. Uric acid (UA) is filtered, reabsorbed and secreted by the kidney. Thus, this study was conducted to assess the serum UA levels in PIH and to evaluate the diagnostic value of serum UA level in PIH. MATERIALS AND METHODS: This is a hospital based comparative cross-sectional study conducted in BPKIHS. Ninety study participants were included; forty five participants were diagnosed of PIH and forty five in control group after obtaining informed consent from study participants from August 2014 to May 2015. Serum UA was done by Uricase method and serum creatinine was done by Jaffe's alkaline picrate method in cobas c311 autoanalyser. Data were expressed in frequency, percentage, mean +/- S.D., median (IQR), and Independent t-test, Mann-Whitney U test were applied. p Value <0.05 is considered to be significant. RESULTS: Mean serum UA levels was higher in PIH compared to control group (5.46 +/- 1.51 vs 4.03 +/- 0.69) respectively. ROC curve demonstrated that serum UA showed a superior diagnostic efficiency (Sensitivity - 79.07%, Specificity - 71.19%) compared to creatinine (Sensitivity 62.75%, Specificity - 27.45%) in PIH respectively. CONCLUSION: The present study shows that serum UA is significantly raised in PIH compared to the control group. Assessment of uric acid is a convenient and cost-effective method for determination of severity in PIH. Thus, serum uric acid can still be used as prevalent marker for risk assessment in PIH. PMID- 28987250 TI - Differences between Metabolically Healthy vs Unhealthy Obese Children and Adolescents. AB - Obesity is on the rise worldwide. An obesity subtype, metabolically healthy obese (MHO), is resilient to unfavorable metabolic and cardiovascular effects. Factors predicting MHO phenotype are not well characterized. We aimed to identify MHO and metabolically unhealthy obese (MUO) children and adolescents with respect to metabolic factors, and to find predictors of MHO subtype. A retrospective chart review was done on children, ages 4-19 years, 99% African-American/Caribbean, with BMI >=95th %tile. MUO was defined as meeting >=1 of the following: fasting glucose >=100 mg/dl, HbA1c >5.6%, BP >=90th %tile, TG >=150 mg/dl, or HDL <40 mg/dl. Study included 189 subjects, 37.6% were MHO and 62.4% MUO. MHO subjects were younger (mean +/- SD, 11.6 +/- 3.3 vs 12.9 +/- 3.2 years; p < 0.009) and had lower BMI %tile (98.4 +/- 1.4 vs 98.8 +/- 2.1; p < 0.04), smaller waist (94.2 +/- 15.2 vs 101.4 +/- 17 cm; p < 0.003) and hip circumferences (105.3 +/- 15.6 vs 113.5 +/- 15.4 cm; p < 0.001), lower fasting insulin (18.5 +/- 10.2 vs 24.2 +/- 14.3 MUU/ml; p < 0.022), and lower HOMA-IR (4.1 +/- 2.4 vs 5.5 +/- 3.6; p < 0.022). Acanthosis nigricans was noted less frequently in MHO than MUO (p < 0.005). In stepwise logistic regression, age and BMI %tile were significant predictors of MHO. We found that 38% of obese children are MHO. They are younger and have lower BMI %tiles. Lifestyle modification initiated at an early age may prevent metabolic abnormalities. PMID- 28987251 TI - The Importance of Mean Neutrophil Volume (MNV) Values in Differential Diagnosis of Bacterial Sepsis. AB - INTRODUCTION: Bloodstream infections are a significant cause of morbidity and mortality in hospitalized patients. Blood cultures and other laboratory tests are used for diagnosis. Among these tests, the mean neutrophil volume (MNV) value is reported as a potential indicator that supports the diagnosis of sepsis. Our study identified the MNV values of patients via microorganisms cultivated from blood cultures and examined the role of these MNV values in the early diagnosis of bloodstream infections. METHODS: Our study surveyed retrospectively 148 adult patient blood culture samples that had been sent to our laboratory. BACTEC 9050 (Becton Dickinson, USA) and BACTEC FX 40 (Becton Dickinson, USA) devices were used in the blood culture isolation procedures. RESULTS: The average MNV value was found to be 159.0 (+11.3) in patients whose sepsis originated from Gram negative bacteria, and the average MNV value was measured as 152.4 (+14.5) among patients whose sepsis originated from Gram-positive bacteria. When comparing groups of patients having Gram-negative bacteria and patients having Gram positive bacteria, a statistically significant difference (p = 0.041) in the MNV values was observed. CONCLUSION: The MNV value was found to be statistically significant in discrimination of Gram-negative and Gram-positive sepsis. Considering these findings, measuring the MNV values can help initiate proper antibiotic treatment more quickly, and we think that this will help lower the mortality rate. However, these findings should be supported with further studies. PMID- 28987252 TI - Cognitive Function Among Obstructive Sleep Apnea Patients in North East Malaysia. AB - INTRODUCTION: Obstructive sleep apnea patients may develop deficits in the cognitive domains of attention, concentration, executive function, verbal and visuospatial memory, constructional abilities, and psychomotor functioning. As cognitive performance will improve with the treatment, early screening for cognitive dysfunction should be done to prevent further deterioration. OBJECTIVE: We aim to evaluate the cognitive function of obstructive sleep apnea patients by using the 'Mini Mental State Examination'. METHODOLOGY: This was a cross sectional study to evaluate the cognitive function of moderate and severe obstructive sleep apnea patients with age ranged from 18 to 60 old who attended our sleep clinic. These patients were confirmed to have moderate and severe obstructive sleep apnea by Type 1 polysomnography (attended full overnight study). The age, gender and ethnicity were noted and other relevant data such as weight, height, body mass index and apnea and hypopnoea index were recorded accordingly. The cognitive function was evaluated using validated Malay version of Mini Mental State Examination which measured 5 areas of cognitive functions comprising orientation, registration, attention and calculation, word recall and language abilities, and visuospatial. RESULTS: A total of 38 patients participated in this study. All 19 patients of moderate group and 14 patients of severe group had normal cognitive function while only 5 patients in severe group had mild cognitive function impairment. There was a statistically significant difference between the moderate group and severe group on cognitive performance (p value = 0.042). CONCLUSIONS: Severe obstructive sleep apnea patients may have impaired cognitive function. Mini Mental State Examination is useful in the screening of cognitive function of obstructive sleep apnea patients but in normal score, more sophisticated test batteries are required as it is unable to identify in 'very minimal' or 'extremely severe' cognitive dysfunction. PMID- 28987253 TI - Hepatitis C Genotype 3 Infection: Pathogenesis and Treatment Horizons. AB - Genotype 3 hepatitis C infection is the second most common genotype worldwide and accounts for most infections in Southeast Asia. It is a particularly ominous genotype because it has been linked to increased mortality, specifically increased late-stage liver events, accelerated development of hepatic fibrosis, and an increased risk of hepatocellular carcinoma. As new treatment regimens for hepatitis C have been emerging, treatment of genotype 3 often requires longer treatment duration with decreased response rates as compared with other genotypes. PMID- 28987254 TI - Primer on Hepatitis C Virus Resistance to Direct-Acting Antiviral Treatment: A Practical Approach for the Treating Physician. AB - Treatment of hepatitis C virus has been vastly transformed by the arrival of all oral, interferon-free, direct-acting antiviral regimens. Despite the high rate of success with these agents, a small portion of treated patients fail therapy and the emergence of viral resistance is the most common cause of treatment failure. Given the error-prone hepatitis C virus polymerase, baseline resistance associated substitutions (RASs) may be present before direct-acting antiviral exposure. Clinicians need to understand the role of baseline RAS testing and the settings and manner in which the treatment regimens need to be customized based on the presence of RASs. PMID- 28987255 TI - Genetic Testing in Liver Disease: What to Order, in Whom, and When. AB - Genetic causes of liver disease lead to a wide range of presentations, from mildly abnormal liver tests to acute liver failure. This article discusses the indications for testing and what to test for hereditary hemochromatosis, progressive familial intrahepatic cholestasis, benign recurrent intrahepatic cholestasis, lysosomal acid lipase deficiency, Gilbert syndrome, alpha-1 antitrypsin deficiency, and Wilson disease. PMID- 28987256 TI - Liver Disease in Patients on Total Parenteral Nutrition. AB - Parenteral nutrition-associated liver disease (PNALD) spectrum ranges from liver enzyme abnormalities to steatosis to fibrosis, and, eventually, cirrhosis from total parenteral nutrition (TPN). The pathophysiology is postulated to be multifactorial. Diagnosis in adults is primarily by exclusion, eliminating other causes of chronic liver disease or cirrhosis, and other factors seen in critically ill or postoperative patients on TPN. Principal treatment is avoiding TPN. If this is not feasible, research supports fish oil-based lipid emulsions in TPN formulations to reduce risk and progression of PNALD. With liver and intestinal failure, liver and intestine transplant is an option. PMID- 28987257 TI - The Liver in Oncology. AB - Gastroenterologists and hepatologists will encounter oncology patients who develop abnormal liver tests, patients with hepatic malignancies, and patients with acute and chronic liver disease who require chemotherapy or immediate evaluation. Chemotherapy can cause liver injury owing to toxic effects or idiosyncratic reactions. Immune checkpoint inhibitors may be associated with autoimmune-mediated liver toxicities. Venoocclusive disease requires immediate evaluation. Nodular regenerative hyperplasia is a chronic progressive disorder. Screening and prophylaxis for reactivation of hepatitis B is important to minimize complications in patients receiving chemotherapy. Patients with metastatic lesions can undergo resection or ablation. Hepatic injury may occur in those receiving radiation-based therapies. PMID- 28987258 TI - An Update on the Treatment and Follow-up of Patients with Primary Biliary Cholangitis. AB - Primary biliary cholangitis (PBC) is an autoimmune liver disease characterized by chronic granulomatous lymphocytic cholangitis of the small bile ducts. PBC was a leading indication for liver transplant in the United States; with early diagnosis and treatment, the majority of patients with PBC have a normal life expectancy. Pathogenesis involves inflammatory damage of bile duct epithelium secondary to innate and adaptive immune responses, and toxicity from accumulated bile acids. Cholestasis and disease progression can lead to cirrhosis. Extrahepatic complications include dyslipidemia, metabolic bone disease, and fat soluble vitamin deficiency. Ursodeoxycholic acid is a well-established therapy. Novel targeted therapeutics are being developed. PMID- 28987259 TI - Primary Sclerosing Cholangitis: What the Gastroenterologist and Hepatologist Needs to Know. AB - Primary sclerosing cholangitis (PSC) is a chronic, idiopathic biliary tract disease characterized by segmental strictures. The disease is progressive with no proven treatments and may eventually lead to cirrhosis and end-stage liver disease. Abrupt changes in liver biochemistries, pain, and/or cholangitis may suggest a dominant stricture amenable to endoscopic therapy or the development of cholangiocarcinoma. Patients with PSC are at increased risk of cholangiocarcinoma. There is a strong association with inflammatory bowel disease, and an associated increased risk of colorectal cancer. Colonoscopy every 1 to 2 years is appropriate. PMID- 28987260 TI - Treatment Strategies for Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis. AB - Nonalcoholic fatty liver disease (NAFLD) is recognized as a global health problem and as a common cause of chronic liver disease. Nonalcoholic steatohepatitis (NASH) carries an increased risk for development of advanced liver disease. Lifestyle modifications with diet and exercise have been the initial management recommendation. However, these changes are difficult to achieve and sustain overtime. There are pharmacologic agents being considered for treatment of NASH. Some target insulin resistance and others focus on oxidative stress, inflammation, apoptosis, and fibrosis. There is a great deal of efforts to develop therapeutic regimens for patients with NASH and NASH with significant fibrosis. PMID- 28987261 TI - Wilson Disease: Diagnosis, Treatment, and Follow-up. AB - Consideration of a diagnosis of Wilson disease is still the critical factor in testing for and establishing disease diagnosis. In association with other clinical and biochemical tests, liver biopsy results and molecular genetic testing can also be used to generate a score for diagnosing Wilson disease. Medical therapy is effective for most patients; liver transplant can rescue those with acute liver failure or those with advanced liver disease who fail to respond to or discontinue medical therapy. Treatment monitoring must be done at regular intervals and includes clinical evaluation, liver tests and blood counts, and copper metabolic parameters. PMID- 28987263 TI - Follow-up of the Post-Liver Transplantation Patient: A Primer for the Practicing Gastroenterologist. AB - The focus in liver transplantation in the next 10 years will likely change from preventing viral disease recurrence to minimizing the toll of rejection and fatty liver disease, minimizing the complications from immunosuppression with withdrawal strategies, and more optimal management of long-term risks, such as malignancy, cardiovascular disease, and renal failure. In addition, now that short-term results (<1 year) have improved significantly, there will be a shift toward improving long-term patient and graft survival, as well as a focus on primary care preventive strategies. PMID- 28987262 TI - Acute Liver Failure. AB - Acute liver failure (ALF) is a life-threatening condition of heterogeneous etiology. Outcomes are better with early recognition and prompt initiation of etiology-specific therapy, intensive care protocols, and liver transplantation (LT). Prognostic scoring systems include the King's College Criteria and Model for End-stage Liver Disease score. Cerebral edema and intracranial hypertension are reasons for high morbidity and mortality; hypertonic saline is suggested for patients with a high risk for developing intracranial hypertension, and when it does, mannitol is recommended as first-line therapy. Extracorporeal liver support system may serve as a bridge to LT and may increase LT-free survival in select cases. PMID- 28987264 TI - Consultations in Liver Disease. PMID- 28987265 TI - Performance and sleepiness in nurses working 12-h day shifts or night shifts in a community hospital. AB - Hospitals are around-the-clock operations and nurses are required to care for patients night and day. The nursing shortage and desire for a more balanced work to-home life has popularized 12-h shifts for nurses. The present study investigated sleep/wake cycles and fatigue levels in 22 nurses working 12-h shifts, comparing day versus night shifts. Nurses (11day shift and 11 night shift) were recruited from a suburban acute-care medical center. Participants wore a wrist activity monitor and kept a diary to track their sleep/wake cycles for 2 weeks. They also completed a fatigue test battery, which included the Psychomotor Vigilance Test (PVT) and the Karolinska Sleepiness Scale (KSS), at the beginning, middle and end of 4 duty shifts. Daily sleep duration was 7.1h on average. No overall difference in mean daily sleep duration was found between nurses working day shifts versus night shifts. Objective performance on the PVT remained relatively good and stable at the start, middle, and end of duty shifts in day shift workers, but gradually degraded across duty time in night shift workers. Compared to day shift workers, night shift workers also exhibited more performance variability among measurement days and between participants at each testing time point. The same pattern was observed for subjective sleepiness on the KSS. However, congruence between objective and subjective measures of fatigue was poor. Our findings suggest a need for organizations to evaluate practices and policies to mitigate the inevitable fatigue that occurs during long night shifts, in order to improve patient and healthcare worker safety. Examination of alternative shift lengths or sanctioned workplace napping may be strategies to consider. PMID- 28987267 TI - The Mobile World of Transposable Elements. PMID- 28987268 TI - Case report of transient mcr-1-haboring Escherichia coli with concurrent Staphylococcus aureus bacteremia in Long Beach, California. AB - A 55-year-old man with history of chronic hepatitis B cirrhosis presented to an emergency department in California with abdominal pain, constipation, and jaundice. The patient developed methicillin-susceptible S. aureus bacteremia with a concurrent transient E. coli. This organism carried mcr-1 in a plasmid similar to other mcr-1-carrying plasmids from the USA. The spread of mcr-1 into carbapenem-resistant isolates is of great concern and monitoring of this resistance mechanism is important. PMID- 28987266 TI - The Genetics of Multiple Sclerosis: From 0 to 200 in 50 Years. AB - Multiple sclerosis (MS) is a common autoimmune disease that targets myelin in the central nervous system (CNS). Multiple genome-wide association studies (GWAS) over the past 10 years have uncovered more than 200 loci that independently contribute to disease pathogenesis. As with many other complex diseases, risk of developing MS is driven by multiple common variants whose biological effects are not immediately clear. Here, we present a historical perspective on the progress made in MS genetics and discuss current work geared towards creating a more complete model that accurately represents the genetic landscape of MS susceptibility. Such a model necessarily includes a better understanding of the individual contributions of each common variant to the cellular phenotypes, and interactions with other genes and with the environment. Future genetic studies in MS will likely focus on the role of rare variants and endophenotypes. PMID- 28987269 TI - Enrollment of Neonates in More Than One Clinical Trial. AB - Because the highest rates of morbidity and mortality in neonates are seen in those born at <32 weeks' gestation, this group has the most urgent need for novel therapies to improve survival and outcome. Legislative efforts in the United States and Europe have attempted to address this issue by requiring the study of drugs, biological and nutritional products, devices, and other therapies in this population through a combination of high-quality regulatory and clinical trials, quality improvement initiatives, and observational studies. Because there are relatively small numbers of very preterm neonates born each year in any 1 country or continent, and because a significant number of clinical trials are recruiting at any 1 time, a neonate may meet enrollment criteria for >1 clinical trial. Neonatal units that have the infrastructure and resources to engage in research frequently face the question of whether it is permissible to enroll a neonate in >1 trial. This article examines the pertinent scientific, ethical, regulatory, and industry issues that should be taken into account when considering enrolling neonates in multiple clinical studies. PMID- 28987270 TI - Involvement of nitrergic system in anticonvulsant effect of zolpidem in lithium pilocarpine induced status epilepticus: Evaluation of iNOS and COX-2 genes expression. AB - This study aims to investigate the role of zolpidem in lithium-pilocarpine induced status epilepticus (SE) and probable mechanisms involved in seizure threshold alteration. In the present study, lithium chloride (127mg/kg) was administered 20h prior to pilocarpine (60mg/kg) to induce SE in adult male Wistar rats. Different doses of zolpidem (0.1, 1, 2, 5, 10mg/kg) were injected 30min before pilocarpine administration. Furthermore, to find out whether nitric oxide (NO) plays a role in the observed effect, L-arginine and L-NAME were injected 15min before zolpidem. Afterward, we identified the particular NO isoform mediating the effect of zolpidem by injecting aminoguanidine (AG) and 7 Nitroindazole (7-NI) 15min prior to zolpidem. Moreover, in both 6 and 24h after pilocarpine injection, experimental groups underwent hippocampectomy to evaluate cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) genes expression by quantitative reverse transcription-PCR (qRT-PCR). Pre-treatment with zolpidem significantly prevented the onset of SE in a dose-dependent manner. AG and L-NAME significantly potentiated the anticonvulsant effect of zolpidem while L-arginine inverted this effect. Our qRT-PCR exerted that there was a continuous elevation of iNOS and COX-2 genes expression over 6 and 24h after pilocarpine administration in SE and L-arginine+Zolpidem groups while in AG/L NAME+Zolpidem and zolpidem groups this upregulation was prevented. Our study indicates that zolpidem prevents the onset of SE through inhibition of iNOS/COX-2 genes upregulation following lithium-pilocarpine administration. Consistent with our results, we suggest that iNOS activation could be probably upstream of COX-2 gene expression. PMID- 28987272 TI - Searching for new pharmacological targets for the treatment of Alzheimer's disease in Down syndrome. AB - Individuals with Down syndrome are at increased risk of developing Alzheimer's disease due to increase gene dosage resulting from chromosome 21 triplication. Although virtually all adults with Down syndrome will exhibit the major neuropathological hallmarks that define Alzheimer's disease, not all of them will develop the clinical symptoms associated with this disorder (i.e. dementia). Therefore, a good understanding of the pathophysiology of Alzheimer's disease in Down syndrome will be crucial for the identification of novel pharmacological targets to develop disease-modifying therapies for the benefit of Down syndrome individuals and for Alzheimer's sufferers alike. The study of biomarkers will also be essential for the development of better screening tools to identify dementia at its incipient stages. This review discusses the best-validated pharmacological targets for the treatment of cognitive impairment and Alzheimer's disease in Down syndrome. We further examine the relevance of newly discovered biological markers for earlier dementia diagnosis in this population. PMID- 28987271 TI - CO-independent modification of K+ channels by tricarbonyldichlororuthenium(II) dimer (CORM-2). AB - Although toxic when inhaled in high concentrations, the gas carbon monoxide (CO) is endogenously produced in mammals, and various beneficial effects are reported. For potential medicinal applications and studying the molecular processes underlying the pharmacological action of CO, so-called CO-releasing molecules (CORMs), such as tricabonyldichlororuthenium(II) dimer (CORM-2), have been developed and widely used. Yet, it is not readily discriminated whether an observed effect of a CORM is caused by the released CO gas, the CORM itself, or any of its intermediate or final breakdown products. Focusing on Ca2+- and voltage-dependent K+ channels (KCa1.1) and voltage-gated K+ channels (Kv1.5, Kv11.1) relevant for cardiac safety pharmacology, we demonstrate that, in most cases, the functional impacts of CORM-2 on these channels are not mediated by CO. Instead, when dissolved in aqueous solutions, CORM-2 has the propensity of forming Ru(CO)2 adducts, preferentially to histidine residues, as demonstrated with synthetic peptides using mass-spectrometry analysis. For KCa1.1 channels we show that H365 and H394 in the cytosolic gating ring structure are affected by CORM-2. For Kv11.1 channels (hERG1) the extracellularly accessible histidines H578 and H587 are CORM-2 targets. The strong CO-independent action of CORM-2 on Kv11.1 and Kv1.5 channels can be completely abolished when CORM-2 is applied in the presence of an excess of free histidine or human serum albumin; cysteine and methionine are further potential targets. Off-site effects similar to those reported here for CORM-2 are found for CORM-3, another ruthenium-based CORM, but are diminished when using iron-based CORM-S1 and absent for manganese-based CORM EDE1. PMID- 28987273 TI - Tranexamic acid impairs hippocampal synaptic transmission mediated by gamma aminobutyric acid receptor type A. AB - High-dose application of tranexamic acid (TXA), a widely used antifibrinolytic drug, can cause seizures in patients undergoing surgery. Mechanistically, seizures are considered to arise from an imbalance between inhibitory and excitatory synaptic transmission, whose main transmitters are gamma-aminobutyric acid (GABA) and glutamate. In the present study, we investigated the effects of TXA on neuronal excitability and synaptic transmission in the hippocampus, a structure that plays a pivotal role in human epilepsy. In acute slices of the murine hippocampus, fast depolarization-mediated imaging signals (FDSs) and postsynaptic currents (PSCs) were recorded using voltage-sensitive dye imaging and whole-cell patch clamp technique, respectively. FDSs and PSCs were evoked upon stimulation of the dentate gyrus and Schaffer collateral/associational commissural pathway, respectively. GABAA, alpha-amino-3-hydroxy-5-methyl-4 isoxazolepropionic acid (AMPA), and N-methyl-d-aspartate (NMDA) receptor-mediated postsynaptic currents were isolated pharmacologically. Application of TXA enhanced FDS propagation in the hippocampus. Neither the resting membrane potential of the investigated neurones nor synaptic transmission mediated by AMPA or NMDA receptors was changed by the application of 1mM TXA. In contrast, TXA dose-dependently reduced GABAA receptor-mediated synaptic transmission. TXA induced the inhibition of GABAA receptor-mediated synaptic transmission in the hippocampus with a potency similar to that of its antagonistic properties against GABAA receptors in the basolateral amygdala (Kratzer et al., 2014). Since impairment of GABAergic transmission is a major cause of epileptic seizures, the observed effect might contribute to the proconvulsive properties of TXA. PMID- 28987275 TI - Bone disease in beta thalassemia patients: past, present and future perspectives. AB - Bone disorders in patients with thalassemia major (TM) and intermedia (TI) constitute complex conditions that result from various factors affecting the growing skeleton. Although much progress has been made in our understanding of the natural history, pathogenesis and clinical manifestations of beta- and deltabeta-thalassemia, bone manifestations remain a puzzle for the clinician. In this review, we outline the key points in the current literature on the pathogenesis and management of bone disease in patients with TM and TI who were conventionally treated in recent decades with frequent blood transfusions and iron chelation. Prevention, early recognition and treatment are the most effective strategies for the management of bone disease in these patients. However, further studies are required to maintain optimal bone health for both TM and TI patients. Studying bone disease in patients with non-transfusion dependent TI, which seems to worsen considerably with age, is important to delineate the effect of the disease itself on bone health without the intervening factors of transfusions, iron intoxication and chelation. PMID- 28987274 TI - Radiation dose and image quality of computed tomography of the supra-aortic arteries: A comparison between single-source and dual-source CT Scanners. AB - PURPOSE: The purpose of this work was to compare the image quality and radiation dose delivered to patients during computed tomography (CT) angiography (CTA) of the supra-aortic arteries using two single-source (SS) and two dual-energy (DE) CT scanners. MATERIAL AND METHODS: In this retrospective study, 120 patients who underwent CTA of supra-aortic arteries were studied using four different types of CT scanners: a sixteen and forty-detector-row SS and two DE CT scanners. Seventy milliters of contrast medium were injected at a flow rate of 4mL/s using a power injector. For each patient the dose-length product (DLP), the volume computed tomography dose index (CDTIvol), the length of the scan and the effective dose (ED) were calculated. Qualitative and quantitative [image noise, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR)] image quality assessment was performed. RESULTS: A statistically significant lower value of the DE compared to the SS technology (P<0.0001) for the CDTI, DLP and ED was found, whereas we did not find any statistically significant difference between the four scanners for the measurements of the image noise, SNR and CNR. CONCLUSION: DS CT scanners allow performing CTAs with a reduced dose compared to SS CT scanner with comparable image quality. PMID- 28987276 TI - Outliers of bone metabolic diseases. PMID- 28987277 TI - Identification and characterization of an angiotensin-converting enzyme inhibitory peptide derived from bovine casein. AB - In this study, we identified a novel angiotensin-I-converting enzyme (ACE) inhibitory peptide, YQKFPQYLQY (YQK), derived from bovine casein. Casein was hydrolyzed using pepsin and trypsin. The target peptide, YQK, was separated from the hydrolysate by ultrafiltration and Sephadex G-15chromatography. The IC50 value of YQK was 11.1MUM. YQK retained its ACE inhibitory activity under various temperature and pH conditions. It was also stable against the digestive enzymes pepsin and trypsin. The Lineweaver-Burk plot suggested that the inhibitory mode of YQK was competitive. Furthermore, its antihypertensive effects in spontaneously hypertensive rats (SHRs) also revealed that oral administration of YQK can significantly decrease systolic blood pressure. These results suggested that YQK may have potential applications in functional foods or pharmaceuticals as an antihypertensive agent. PMID- 28987278 TI - Cationic peptides from peptic hydrolysates of rice endosperm protein exhibit antimicrobial, LPS-neutralizing, and angiogenic activities. AB - In this study, we hydrolyzed rice endosperm protein (REP) with pepsin and generated 20 fractions containing multifunctional cationic peptides with varying isoelectric point (pI) values using ampholyte-free isoelectric focusing (autofocusing). Subsequently, we determined antimicrobial activities of each fraction against the pathogens Prophyromonas gingivalis, Propionibacterium acnes, Streptocossus mutans, and Candida albicans. Fractions 18, 19, and 20 had pI values greater than 12 and exhibited antimicrobial activity against P. gingivalis, P. acnes, and C. albicans, but not against S. mutans. In further experiments, we purified and identified cationic peptides from fractions 18, 19, and 20 using reversed-phase high-performance liquid chromatography and matrix assisted laser/desorption ionization-time-of-flight mass spectroscopy. We also chemically synthesized five identified peptides (RSVSKSR, RRVIEPR, ERFQPMFRRPG, RVRQNIDNPNRADTYNPRAG, and VVRRVIEPRGLL) with pI values greater than 10.5 and evaluated antimicrobial, lipopolysaccharide (LPS)-neutralizing, and angiogenic activities. Among these synthetic peptides, only VVRRVIEPRGLL exhibited antimicrobial activity against P. gingivalis, with an IC50 value of 87MUM. However, all five cationic peptides exhibited LPS-neutralizing and angiogenic activities with little or no hemolytic activity against mammalian red blood cells at functional concentrations. These present data show dual or multiple functions of the five identified cationic peptides with little or no hemolytic activity. Therefore, fractions containing cationic peptides from REP hydrolysates have the potential to be used as dietary supplements and functional ingredients in food products. PMID- 28987279 TI - Long-term Evaluation of the Ross Procedure in Acute Infective Endocarditis. AB - Optimal valve substitute for young patients with aortic valve endocarditis remains controversial. Given its better resistance to infection, the Ross procedure is an attractive alternative to prosthetic valve replacement or homograft implantation. The objective of this study was to assess long-term outcomes of the Ross procedure in this indication. From January 1991 to April 2017, 190 patients underwent a Ross procedure at our institution. Acute endocarditis was the indication for operation in 19 patients, including 6 patients with a bicuspid aortic valve. The pulmonary autograft was implanted as freestanding root replacement in all patients. The clinical follow-up is 100% complete, with a mean of 12.0 +/- 5.7 years. The mean age of the study population was 35.9 +/- 11.5 years. Moderate or severe aortic regurgitation was present in 84.2% of the patients. Systemic embolization had occurred in 36.8% of the patients. The mean aortic cross-clamp time was 126 +/- 24 minutes. The median length of stay on the intensive care unit was 1 day. Mortality at 30 days was 5.3% (1 patient with gastrointestinal bleeding). Echocardiography at hospital discharge documented no or trivial aortic regurgitation in all patients. No case of recurrent endocarditis affecting the autograft occurred. One patient (0.4% per patient-year) was reoperated 1.8 years after the Ross procedure for homograft endocarditis. Three patients (15.8%) were reoperated for autograft aneurysm. The Ross procedure is a safe and effective alternative to prosthetic valve replacement or homograft implantation in selected young patients with acute endocarditis with a low rate of recurrent infection. PMID- 28987280 TI - A Stopping Guideline for Pulmonary Heart Valve Premarket Approval Studies. PMID- 28987281 TI - The effects of the 5-HT7 receptor on hippocampal long-term potentiation and apoptosis in a rat model of Alzheimer's disease. AB - Alzheimer's disease (AD) is the most common neurodegenerative disorder involving synaptic loss and impairments in learning and memory. Long-term potentiation (LTP) of synaptic function is a model of learning- and memory-related neural plasticity, of which serotonin (5-HT) is a key modulator in the hippocampus. As the 5-HT7 receptor subtype is implicated in hippocampal neuronal function, dendritic rearrangement, and neurogenesis, the aim of this study was to assess the effect of 5-HT7 receptor activation on hippocampal synaptic plasticity and apoptosis in a rat model of AD. AD was induced via intracerebroventricular (icv) administration of streptozotocin (STZ). Forty adult male Wistar rats were divided into naive control, sham-operated, AD+saline (1MUL icv for 30days), and AD+AS19 (a selective 5-HT7 receptor agonist, 1MUg/MUL, icv for 30days) groups. Following the treatment period, rats were anesthetized and placed in a stereotaxic apparatus. LTP was induced by high-frequency stimulation of the perforant pathway. The population spike (PS) and field excitatory postsynaptic potentials (fEPSP) in the dentate gyrus of the hippocampus were measured. Then, neuronal apoptosis was detected using the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. The PS and fEPSP of the AD+saline group were significantly decreased compared to the control and sham-operated groups. Moreover, the PS and fEPSP of the AD+AS19 group were significantly increased compared to the AD+saline group. We found that STZ-induced AD impaired LTP in the dentate granule cells. One month of AS19 treatment restored hippocampal LTP and reduced neuronal apoptosis in the AD+AS19 group. These findings suggest that 5-HT7 receptor activation by AS19 improves synaptic dysfunction in a rat model of AD via reduction of apoptosis in the hippocampus and it could potentially prevent the progression of AD. PMID- 28987282 TI - Antidepressants promote formation of heterocomplexes of dopamine D2 and somatostatin subtype 5 receptors in the mouse striatum. AB - The interaction between the dopaminergic and somatostatinergic systems is considered to play a potential role in mood regulation. Chronic administration of antidepressants influences release of both neurotransmitters. The molecular basis of the functional cooperation may stem from the physical interaction of somatostatin receptor subtypes and dopamine D2 receptors since they colocalize in striatal interneurons and were shown to undergo ligand-dependent heterodimerization in heterologous expression systems. In present study we adapted in situ proximity ligation assay to investigate the occurrence of D2-Sst5 receptor heterocomplexes, and their possible alterations in the striatum of mice treated acutely and repeatedly (21days) with antidepressant drugs of different pharmacological profiles (escitalopram and desipramine). Additionally we analysed number of heterocomplexes in primary striatal neuronal cultures incubated with both antidepressant drugs for 1h and 6days. The studies revealed that antidepressants increase formation of D2-Sst5 receptors heterodimers. These findings provide interesting evidence that dopamine D2 and somatostatin Sst5 heterodimers may be considered as potential mediators of antidepressant effects, since the heterodimerization of these receptors occurs in native brain tissue as well as in primary striatal neuronal cultures where receptors are expressed at physiological levels. PMID- 28987283 TI - Follow up study: The influence of rTMS with high and low frequency stimulation on motor and executive function in Parkinson's disease. AB - BACKGROUND: rTMS may influence on both cognitive and motor function in PD but the daily routine and the predictors of responders to rTMS are not known. OBJECTIVE/HYPOTHESIS: We hypothesized that the frequency and intensity of stimulation somehow relate to each other. Our goal was to select the optimal frequency with low intensity for PD. We clarified the importance of age in the effect of rTMS. METHODS: A total sixty-six patients with PD were included in the study. In an open investigation, randomly selected patients were divided into three groups. The effects of 1Hz (N=28), 5Hz (N=13) and 5+1Hz (N=25) frequency at low intensity over each DLPFC and the brain stem for 7days were compared. Patients were followed for six months. UPDRS, the Trail Making Test, and dual tasks were applied. Patients <=65years >65yrs were compared. Data were analyzed by repeated measure ANOVA. RESULTS: Only 1Hz had an effect on motor scores. Before the trial patients<=65 yrs had UPDRS total scores of 30.3+/-16.9, after 1 month: 17.8+/-8.9 p<0.001, after 6 months 18.3+/-8.8 p<0.001. Improvement of patients >65yrs was observed after one month (p<0.01). Executive function >65yrs (N=16) was significantly worse compared with C (N=15) and it was improved temporarily by 1Hz. Five Hertz and 5+1Hz did not cause improvement. CONCLUSION: One Hertz with proper intensity has a good outcome in PD. Patients >65yrs show deterioration in their executive function and they have shorter duration in their therapeutic effect of rTMS. This study draws attention to the importance of stimulation intensity and age as a predictor of the effect of rTMS. PMID- 28987284 TI - Lentivirus carrying the NeuroD1 gene promotes the conversion from glial cells into neurons in a spinal cord injury model. AB - In this study, we aimed to reprogram reactive glial cells into neural stem cells and neurons in vivo, by up-regulating NeuroD1. 60 rats were randomly divided into three groups with equal numbers. All rats received a spinal cord injury. Group A received only normal saline injection. Group B received unloaded lentivirus injection. Group C received NeuroD1 recombinant lentivirus injection. The BBB scores of the animals were documented at 3, 7, 14, 21days after SCI. 5 random rats of each group were removed at those timings after SCI and sacrificed. In the spinal cord slices, the numbers and morphology of neural stem cells, immature neurons and mature neurons were examined after immunohistochemical staining. Except day 3 after SCI, the BBB scores of group C on days 7, 14 and 21 were significantly higher than the other two groups (P<0.05). Compared with the group A and B, a remarkable increase was noticed in the number of positive cells in the group C (P<0.05). These findings suggest that NeuroD1 up-regulated cells can be reprogrammed into neural stem cells, immature and functional neurons. It may be possible to replace neurons after injury by endogenous means, as a first step toward spinal cord repair. PMID- 28987285 TI - Heterotopic ossification and the elucidation of pathologic differentiation. AB - Tissue regeneration following acute or persistent inflammation can manifest a spectrum of phenotypes ranging from the adaptive to the pathologic. Heterotopic Ossification (HO), the endochondral formation of bone within soft-tissue structures following severe injury serves as a prominent example of pathologic differentiation; and remains a persistent clinical issue incurring significant patient morbidity and expense to adequately diagnose and treat. The pathogenesis of HO provides an intriguing opportunity to better characterize the cellular and cell-signaling contributors to aberrant differentiation. Indeed, recent work has continued to resolve the unique cellular lineages, and causative pathways responsible for ectopic bone development yielding promising avenues for the development of novel therapeutic strategies shown to be successful in analogous animal models of HO development. This review details advances in the understanding of HO in the context of inciting inflammation, and explains how these advances inform the current standards of diagnosis and treatment. PMID- 28987287 TI - Patient-centered clinical trials. AB - We apply Bayesian decision analysis (BDA) to incorporate patient preferences in the regulatory approval process for new therapies. By assigning weights to type I and type II errors based on patient preferences, the significance level (alpha) and power (1-beta) of a randomized clinical trial (RCT) for a new therapy can be optimized to maximize the value to current and future patients and, consequently, to public health. We find that for weight-loss devices, potentially effective low risk treatments have optimal alphas larger than the traditional one-sided significance level of 5%, whereas potentially less effective and riskier treatments have optimal alphas below 5%. Moreover, the optimal RCT design, including trial size, varies with the risk aversion and time-to-access preferences and the medical need of the target population. PMID- 28987286 TI - Determination of sex differences of human cadaveric mandibular condyles using statistical shape and trait modeling. AB - The objective of this study was to elucidate sex differences in the anatomy of human temporomandibular joint mandibular condyles using a statistical shape and trait model (SSTM). Mandibles were obtained from 16 human cadavers (79+/ 13years). The condyles were scanned using micro-computed tomography with 27MUm resolution. An image processing algorithm was used to segment the bone, determine the border of the entire mandibular condyle and trabecular bone compartments, and create triangulated meshes of the compartments. One subject was chosen as the template and was registered to the other individuals using a coherence point drift algorithm. This process positioned all vertices at corresponding anatomic locations. For the trabecular bone region, around each vertex position, the average bone image intensity, which is proportional to bone density, and microstructural traits, including trabecular bone volume fraction, thickness, separation, connectivity, and connectivity density were calculated. For the entire mandibular condyle mesh, the surface vertices were extracted to represent the overall anatomy of the condyle. Using a SSTM, the shape and trait information was reduced to a small set of independent and uncorrelated variables for each individual. Wilcoxon rank sum tests were used to test for differences in the variables between sexes. A lasso approach was used to determine a set of variables that differentiate between sexes. Male condyles were on average larger than female condyles, with complex differences in the microstructural traits. Two out of 15 principal components were statistically different between males and females (p<0.1). The lasso approach determined a set of 7 principal components that fully described the complex shape and trait differences between males and females. A SSTM was able to determine sex-dependent differences in the shape of the mandibular condyle. These differences may alter the biomechanics of the joint and contribute to the development of temporomandibular joint disease. PMID- 28987288 TI - Relict plastidic metabolic process as a potential therapeutic target. AB - The alignment of the evolutionary history of parasites with that of plants provides a different panorama in the drug development process. The housing of different metabolic processes, essential for parasite survival, adds to the indispensability of the apicoplast. The different pathways responsible for fueling the apicoplast and parasite offer a myriad of proteins responsible for the apicoplast function. The studies emphasizing the target-based approaches might help in the discovery of antimalarials. The different putative drug targets and their roles are highlighted. In addition, the origin of the apicoplast and metabolic processes are reviewed and the different drugs acting upon the enzymes of the apicoplast are discussed. PMID- 28987289 TI - Nonclinical data supporting orphan medicinal product designations: lessons from rare neurological conditions. AB - Here, we provide an in-depth literature and experience-based review of nonclinical models and data used to support orphan medicinal product designations (OMPDs) in rare neurodegenerative conditions. The Committee for Orphan Medicinal Products (COMP) of the European Medicines Agency updates its assessment processes based on scientific progress and aims to provide transparent criteria required in support of OMPDs. Thus, we also provide an updated analysis of existing nonclinical models in selected conditions and identify key features of nonclinical studies that are crucial for the support of OMPDs. This could not only inform future drug development in rare neurological conditions, but also indicate areas where the use of nonclinical models can be made more efficient. PMID- 28987290 TI - Medical Student Experiences on Consultation-Liaison Psychiatry Rotations: A Nationwide Survey. AB - BACKGROUND: Consultation-liaison (C-L) psychiatry clerkship rotations may improve medical students' understanding of psychiatric principles relevant to the settings in which they will ultimately practice. This study aimed to characterize students' experiences on C-L rotations. METHODS: This cross-sectional survey study, sponsored by the Academy of Psychosomatic Medicine Subcommittee on Medical Student Education, was conducted at 5 US medical schools between 2012 and 2016. After the C-L rotation, students completed a voluntary 17-item survey. RESULTS: A total of 235 surveys were collected (mean response rate = 92%). The most frequently endorsed benefit of C-L was learning to manage psychiatric disorders in the context of medical illness (89%). The most frequently endorsed drawback was inconsistent/excessively variable workload (40%). Overall, 82% of respondents recommended C-L to other students; 80% reported that the ideal clerkship would include exposure to both C-L and inpatient psychiatry. Overall, 38% reported that their C-L experience increased their interest in psychiatry as a career. Effect of C-L on interest in psychiatry did not differ by study site, age, sex, clerkship length, or time spent on C-L. Respondents who noted more positive role modeling on C-L compared to other clerkship rotations were more likely to report increased interest in a psychiatry career (odds ratio = 2.70). CONCLUSIONS: Most medical students perceive C-L rotations favorably. Positive role modeling may increase their consideration of psychiatry specialization. The findings that C-L rotation length did not correlate with attitudes and that most students preferred exposure to both inpatient and C-L psychiatry suggest that C-L exposure can beneficially be integrated into core clerkships containing other elements. PMID- 28987291 TI - Severe infectious mononucleosis in immunocompetent adults. AB - OBJECTIVES: To determine the risk factors for severe infectious mononucleosis (IM) occurrence in immunocompetent adults. METHODS: We performed a multicenter, retrospective case series including immunocompetent adults presenting with confirmed IM between 2001 and 2011. Severe presentations were compared with uncomplicated presentations using Stata(r) 9 software. The significance level was set at 5%. RESULTS: In univariate analysis, age over 30 years (n=13 or 41.9% vs. n=5 or 12.8%; P=0.006), prior use of non-steroidal anti-inflammatory drugs (NSAIDs) (n=7 or 87.5% vs. n=1 or 12.5%; P=0.009), and smoking (n=13 or 68.4% vs. n=6 or 31.6%; P=0.013) were associated with severe IM onset. In multivariate analysis, only age over 30 years (OR=3.55; P=0.05) and prior use of NSAIDs (OR=15; P=0.05) remained associated with severe IM onset, without reaching significance level (P=0.05). CONCLUSION: Our study confirmed that age over 30 years is a risk factor for severe IM onset. Prior use of NSAIDs also seems to be correlated with severe presentations. This new data needs to be confirmed in a prospective study. PMID- 28987292 TI - Viral prevalence and laboratory investigations of gastroenteritis in institutions for dependent people. AB - OBJECTIVES: Viruses are recognized as important agents of gastroenteritis outbreaks in institutions caring for dependent people. We aimed to define norovirus (NoV) and rotavirus (RV) immunochromatographic tests (ICT) and reverse transcription-polymerase chain reaction (RT-PCR) used in gastroenteritis investigations. METHODS: Fourteen sites were monitored from 2010 to 2015, with 360 laboratory investigations. Twenty-two outbreaks and 44 sporadic case patients were investigated with ICTs (114 NoVs and 80 RVs) and RT-PCRs (114 NoVs and 52 RVs). RESULTS: ICTs were useful during outbreaks (identification of NoVs and RVs in respectively 76.5% and 75.0% of episodes) despite the NoV sensitivity limit (55.1%) and the four RV false positive results observed for 10 samples. Given the NoV ICT performance and the observed variations of the NoV and RV prevalence (between 20.0% and 5.0%), ICTs are not appropriate to identify sporadic gastroenteritis case patients. Positive predictive values <60.0% were observed when the prevalence of RV and NoV was low (<5.0%). NoV and RV RT-PCR indications are sporadic gastroenteritis case patients, negative NoV and RV ICT during outbreaks, control of positive RV ICT in cases of suspected NoV and RV co circulation, patients with long symptom duration, and NoV genogroup and genotype identifications (infection control and epidemiological surveillance). Inclusion of patients with specific clinical symptoms is recommended irrespective of the technique. CONCLUSION: On the basis of the ICT limits identified in this work, RT PCR development seems essential to improve viral gastroenteritis investigations in institutions caring for dependent people. PMID- 28987293 TI - Society of Family Planning Guidelines: Postplacental insertion of intrauterine devices. AB - Postplacental intrauterine device (IUD) placement, defined as IUD placement within 10 min after delivery of the placenta, is an appealing strategy for increasing access to postpartum IUDs because it does not require a separate postpartum visit. These guidelines present an evidence-based assessment of postplacental IUD placement after vaginal and cesarean delivery. Postplacental IUD insertion is safe and does not have higher risks of complications than interval insertion. Most studies find that the risk of IUD expulsion is higher after postplacental insertion than after interval insertion for both vaginal and cesarean deliveries. Most studies find higher rates of expulsion after vaginal delivery than after cesarean delivery. However, expulsion rates vary widely across studies, without clear evidence about the factors that may influence expulsion. In settings where replacement of expelled IUDs is available, patient populations with low rates of return for the postpartum visit are most likely to benefit from provision of postplacental IUD placement with appropriate counseling about risks and benefits. PMID- 28987294 TI - Network pharmacology-based approach of novel traditional Chinese medicine formula for treatment of acute skin inflammation in silico. AB - Matrix metalloproteinase-9 (MMP-9) appears to play an important role in acute skin inflammation. Subantimicrobial dose of tetracycline has been demonstrated to inhibit the activity of MMP-9 protein. However, long-term use tetracycline will induce side effect. The catalytic site of MMP-9 is located at zinc-binding amino acids, His401, His405 and His411. We attempted to search novel medicine formula as MMP-9 inhibitors from traditional Chinese medicine (TCM) database by using in silico studies. We utilized high-throughput virtual screening to find which natural compounds could bind to the zinc-binding site. The quantitative structure activity relationship (QSAR) models, which constructed by scaffold of MMP-9 inhibitors and its activities, were employed to predict the bio-activity of the natural compounds for MMP-9. The results showed that Celacinnine, Lobelanidine and Celallocinnine were qualified to interact with zinc-binding site and displayed well predictive activity. We found that celallocinnine was the best TCM compound for zinc binging sites of MMP-9 because the stable interactions were observed under dynamic condition. In addition, Celacinnine and Lobelanidine could interact with MMP-9 related protein that identified by drug-target interaction network analysis. Thus, we suggested the herbs Hypericum patulum, Sedum acre, and Tripterygium wilfordii that containing Celallocinnine, Celacinnine and Lobelanidine might be a novel medicine formula to avoid the side effect of tetracycline and increase the efficacy of treatment. PMID- 28987295 TI - Evaluation of degradation mechanism of chlorhexidine by means of Density Functional Theory calculations. AB - Chlorhexidine (CHD), a germicidal drug, has degradation products that can be hemotoxic and carcinogenic. However, there is no consensus in literature about the degradation pathway. In order to shed light on that mechanism, we have employed Density Functional Theory to study reactants, in different protonation states, products and intermediates involved in the different pathways. Based on free energy values comparison and frontier molecular orbital analysis, we have obtained the most stable structures in each protonation state. CHD in saturated form has HOMO localized in one p-chloroaniline, and, due to molecule's symmetry, HOMO-1 has contributions from the other side of the molecule, but mainly from the biguanide portion of the molecule, instead of from the p-chloroaniline. For the saturated form, we have studied two possible degradation pathways, starting from the monoprotonated structure, and three pathways starting from the neutral structure. We found out that the mechanisms proposed in literature, whose pathways lead to p-chloroaniline (PCA) formation in a smaller number of steps, are more likely than the mechanisms with more intermediate steps or pathways that do not predict PCA formation. Also, based on free energy results, we have found that the formation of another sub-product (PBG-AU) is favorable as well. PMID- 28987296 TI - Yellow phosphorus-induced Brugada phenocopy. AB - BACKGROUND: Metallic phosphides (of aluminum and phosphide) and yellow phosphorus are commonly used rodenticide compounds in developing countries. Toxicity of yellow phosphorus mostly pertains to the liver, kidney, heart, pancreas and the brain. Cardiotoxicity with associated Brugada ECG pattern has been reported only in poisoning with metallic phosphides. METHODS AND RESULTS: Brugada phenocopy and hepatic dysfunction were observed in a 29-year-old male following yellow phosphorus consumption. He had both type 1 (day1) and type 2 (day2) Brugada patterns in the electrocardiogram, which resolved spontaneously by the third day without hemodynamic compromise. CONCLUSION: Toxins such as aluminum and zinc phosphide have been reported to induce Brugada ECG patterns due to the generation of phosphine. We report the first case of yellow phosphorus-related Brugada phenocopy, without hemodynamic compromise or malignant arrhythmia. PMID- 28987297 TI - Enhanced Versus Basic Referral for Intimate Partner Violence in an Urban Emergency Department Setting. AB - BACKGROUND: Victims of intimate partner violence (IPV) frequently do not disclose abuse to medical providers. Therefore, research has examined the most effective screening and referral methods to help identify victims of abuse and connect them to needed resources. OBJECTIVES: To determine the efficacy of referrals intended to connect IPV victims with behavioral health resources, while taking into consideration demographic and mental health variables. METHODS: We examined a convenience sample of medically stable individuals in an emergency department setting. Participants were given the Mini-International Neuropsychiatric Interview and Partner Violence Screen measures to assess mental health and IPV victimization. Individuals that screened positive were randomized to a basic or enhanced referral and given a follow-up interview to determine referral success. Referrals were considered successful if an individual scheduled an appointment with provided behavioral health resources within the follow-up interval. RESULTS: Two-hundred and one individuals were enrolled. Forty-one (20.4%) participants screened positive for IPV victimization. Male and female participants in the enhanced referral group were more likely to have a successful referral than those in the basic referral group, with a large effect size such that 72.7% of participants in the enhanced referral and 15.7% of participants in the basic referral group contacted referral resources. Both referral type and marital status significantly predicted referral success. CONCLUSION: Comorbidity with mental health concerns measured as high within those that screened positive for IPV victimization. The enhanced referral showed to be an effective way to encourage participants to contact behavioral health resources. PMID- 28987298 TI - Palliative Care Symptom Management in The Emergency Department: The ABC's of Symptom Management for The Emergency Physician. AB - BACKGROUND: Palliative care is a rapidly evolving area of emergency medicine. With an estimated 5,000 to 10,000 baby boomers per day reaching retirement age, emergency departments (EDs) are treating more patients with chronic and serious disease. Palliative care offers comprehensive care for patients with advanced medical illness, aims to alleviate suffering and improve quality of life, and plays an important role in caring for these patients in the ED. OBJECTIVES: We sought to increase the emergency physician's knowledge of and comfort with symptom control in palliative and hospice patients. DISCUSSION: Having the skills to deliver efficient and appropriate palliative and hospice care is imperative for emergency physicians. Palliative care should be considered in any patient suffering from symptoms of a life-limiting illness, whereas hospice care should be considered in the patient with likely <6 months left to live. Palliative care is appropriate earlier in the course of disease, and is appropriate when the practitioner would not be surprised if the patient died in the next 2 years ("The Surprise Question"). This article discusses management in the ED of pain, nausea, dyspnea, agitation, and oral secretions in patients appropriate for hospice and palliative care. CONCLUSION: The need for palliative and hospice care in the ED is increasing, requiring that emergency physicians be familiar with palliative and hospice care and competent in the delivery of rapid symptom management in patients with severe and life-limiting disease. PMID- 28987299 TI - "Screaming your Lungs Out!" A Case of Boy Band-Induced Pneumothorax, Pneumomediastinum, and Pneumoretropharyngeum. PMID- 28987300 TI - Dermal Injury Caused by Hydrogen Peroxide. PMID- 28987301 TI - A Young Man with Acute Chest Pain. PMID- 28987303 TI - The Kager's Fat Pad Sign. PMID- 28987302 TI - Ricin Poisoning after Oral Ingestion of Castor Beans: A Case Report and Review of the Literature and Laboratory Testing. AB - BACKGROUND: Ricin is a protein toxin derived from the castor bean plant Ricinus communis. Several cases secondary to its consumption have been published and, more recently, its use as a potential bioterrorism agent has also been reported. Oral absorption of ricin is highly erratic, leading to a wide spectrum of symptoms. In addition, conventional urine drug screening tests will not be able to detect this compound, posing a diagnostic challenge. CASE REPORT: A male teenager intended to die by ingesting 200 castor beans after mixing and blending them with juice. Eight hours later, he presented with weakness, light-headedness, nausea, and vomiting and sought medical treatment. The patient was admitted and treated conservatively. An immune-based standard urine toxicology drug screen panel was reported as negative. A comprehensive untargeted urine drug screen test showed the presence of ricinine, a surrogate marker of ricin intoxication. He was transferred to the psychiatric service 3 days after admission. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case highlights the importance of knowing the peculiar pharmacokinetic properties of ricin after oral ingestion of castor beans and toxin release through mastication. Emergency physicians should be aware that oral absorption of ricin is dependent on several factors, such type and size of seeds and the geographic harvesting region, making it extremely difficult to estimate its lethality based solely on the number of ingested beans. Finally, comprehensive untargeted urine drug screening testing is highly valuable as a diagnostic tool in this context. PMID- 28987304 TI - Death from Ingestion of E-Liquid. AB - BACKGROUND: The use of e-liquids is becoming more prevalent. There is a risk that such liquids may be ingested by mouth rather than being vaped/ inhaled. Due to the high concentration of drugs such as nicotine in these liquids, there may be toxic, and possibly fatal consequences. CASE REPORT: We report the death of a 32 year-old male who ingested nicotine-containing e-liquid while under the influence of alcohol. A serum sample taken 24 h after collapse contained nicotine at a concentration of 1600 ng/mL of nicotine. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Death secondary to e-liquid ingestion is still very rare, but has the potential for causing deaths due to the easy access of such liquids to the general public. Such toxicity should be considered in individuals who present in the early phases with symptoms of stimulant toxicity, but also in the latter phase where there may be autonomic depressive effects. PMID- 28987305 TI - Unintentional Marijuana Exposure Presenting as Altered Mental Status in the Pediatric Emergency Department: A Case Series. AB - BACKGROUND: Unintentional tetrahydrocannabinol (THC) exposure in pediatric patients can present as altered mental status. Altered mental status in a pediatric patient often leads to invasive diagnostic testing. CASE REPORT: The following cases describe 3 pediatric patients in Washington state who presented to a tertiary care children's hospital emergency department (ED) with altered mental status, later found to have urine toxicology screening positive for inactive THC metabolite (positive THC toxicology screen). Case 1 is a 6-year-old boy who presented with vomiting, lethargy, and hallucinations. Case 2 is a 5-year old girl who presented with nausea, slurred speech, ataxia, and lethargy in the setting of a minor head injury. Case 3 is a 7-month-old boy who presented with vomiting and lethargy in the setting of a minor fall the day prior to ED evaluation. All children had extensive work-ups before the diagnosis was made; 2 were discharged home and 1 was admitted to the pediatric intensive care unit. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: As access to marijuana increases with growing legalization, it is important to be familiar with state marijuana legislation, to consider and ask families about access to marijuana products as a potential contributor to altered mental status, and to be aware of potential caretaker reluctance regarding disclosure of marijuana use secondary to perceived stigma. Maintaining awareness of the clinical effects of THC exposure in children may limit invasive testing in a hemodynamically stable child with altered mental status. PMID- 28987306 TI - Klebsiella pneumoniae Invasive Liver Abscess Syndrome and Endophthalmitis. PMID- 28987307 TI - A Young Man with Abdominal Pain and Distension. PMID- 28987308 TI - Ambulance Crash in a Rural Area of Thailand. AB - BACKGROUND: Ambulance crashes delay patient transfer and endanger patients, ambulance crews, and other road users. In low- and middle-income countries, where motor vehicle crash rates are typically high, ambulances have a high risk of being involved in a crash. This case report describes an ambulance crash in Thailand to elucidate modifiable problems in current protocols and practices of emergency medical services. CASE REPORT: In November 2016, a 28-year-old male driver of an ambulance died in a crash while transferring a female patient with dizziness to a rural hospital. The driver and another ambulance crew member were sitting in the front seats unrestrained. The other occupants were in the patient compartment unrestrained. The driver was driving the ambulance within the speed limit. He made a sharp turn trying to evade a dog, and the ambulance crashed head on into a roadside tree. The cabin sustained severe damage, and the occupants in the patient compartment were struck against the compartment wall and were struck by unsecured equipment and the stretcher. The driver sustained a severe brain injury. The other occupants, including the female patient, sustained minor injuries. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case raises safety issues concerning the following aspects of ambulance operations in low- and middle-income countries: speed limit, safety device use, seatbelt use, securing equipment, and vehicle safety standards. Systematic measures to change protocols or even legislation, as well as data collection, are required to address these issues. PMID- 28987309 TI - Risperidone in the Emergency Setting is Associated with More Hypotension in Elderly Patients. AB - BACKGROUND: Expert consensus panels have recommended risperidone as first-line treatment for agitation of psychiatric origin. However, there are few if any studies on this medication in the emergency setting. OBJECTIVES: To assess the hemodynamic effects of risperidone in an emergency department (ED) setting, stratified by age. METHODS: This is a structured chart review of all patients who received oral risperidone over a 6-year period in an ED setting, excluding patients who received this medication as a prescription refill. Vital signs were analyzed for this subset prior to and after medication administration, and changes in vital signs were stratified by age. RESULTS: The median dose of risperidone was less in patients aged > 65 years. However, the median drop in systolic blood pressure was larger in this age group compared with younger patients. CONCLUSIONS: Clinicians tend to be more cautious with dosing of risperidone to geriatric patients in the ED. Despite this, decreases in systolic blood pressure are larger and more frequent in this age group. When possible, clinicians should consider or attempt nonpharmacologic methods of agitation treatment prior to administering medications such as risperidone to elderly patients. PMID- 28987310 TI - Spontaneous Subclavian Artery Dissection Causing Ischemia of the Medulla Oblongata and Cerebellum. AB - BACKGROUND: Spontaneous subclavian artery dissection is a rare etiology. Spontaneous artery dissection causing brain ischemia is rare in all ischemic strokes. However, in young to middle-aged patients with brain ischemia, spontaneous carotid or vertebral artery dissection causing ischemic stroke accounts for 10-25%. CASE REPORT: A 58-year-old man with a history of hypertension presented to the Emergency Department with a sudden onset of left arm paresthesia and numbness followed by symptoms of vertigo and vomiting. A neurological examination showed left-arm paresthesia, horizontal-rotational nystagmus, and left-side dysmetria according to a finger-to-nose test. Contrast enhanced computed tomography showed left subclavian artery dissection. Diffusion weighted imaging demonstrated hyperintensity in the left medulla oblongata and inferior part of the cerebellum. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Spontaneous artery dissection is an important etiology of ischemic stroke among young patients. Cervical magnetic resonance angiography is the gold standard for the diagnosis of arterial dissection. Cervical disc disease is a common etiology in a patient with neck and shoulder pain without cause or neurologic symptoms, when cervical MRI is negative, however, spontaneous subclavian artery dissection should be considered in the differential diagnosis when a patient, especially in a case of younger patient, presents with acute new onset neck and shoulder pain followed by the onset of neurological symptoms. PMID- 28987311 TI - Advances in Diabetes Pharmacotherapy: An Update for the Emergency Provider. AB - BACKGROUND: Diabetes mellitus is a disease that affects millions of Americans, and its prevalence is only anticipated to increase in coming years. It is estimated that diabetes-related visits account for 1% of all emergency department (ED) encounters. In recent years, there have been several new categories of medications approved for the treatment of diabetes, including new insulins, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, an amylin analogue, and sodium-glucose cotransporter-2 inhibitors. OBJECTIVE OF THE REVIEW: This review presents recently approved agents to treat diabetes, with a focus on basic mechanism, place in therapy, and toxicities the ED provider may encounter. DISCUSSION: Many of these new therapies have been incorporated as first- and second-line agents for the management of diabetes. Recently approved diabetes medications often have different mechanisms of action and adverse effect and overdose profiles compared to traditional agents, such as sulfonylureas and metformin. CONCLUSIONS: Emergency providers will encounter patients taking these newly approved medications, as well as treat those presenting with adverse effects and overdoses from them. As such, emergency providers must have a basic understanding of these new therapies so that they can optimally care for diabetic patients. PMID- 28987312 TI - Incidental Findings on Pediatric Abdominal Computed Tomography At A Pediatric Trauma Center. AB - BACKGROUND: The increasing availability and use of computed tomography (CT) in pediatric abdominal trauma has increased the detection of incidental findings. While some of these findings are benign, others may require further evaluation for possible clinical importance. OBJECTIVES: This study aimed to identify the frequency and type of incidental findings and their need for follow-up on abdominal CT in patients at a pediatric trauma center. METHODS: This was a retrospective, observational study on trauma patients <=21 years of age who presented to the emergency department between January 1, 2004 and July 31, 2016 and underwent CT scans of the abdomen and pelvis. Findings were classified as benign anatomic variants, benign pathologic lesions, and pathologic lesions requiring additional work-up. RESULTS: There were 1073 patients included in the study population, with a mean age of 15.5 years; 707 (66%) were males. A total of 418 incidental findings were identified in 345 patients. Of these, 290 (69%) were benign and 60 (14%) were likely benign pathologic that required possible outpatient monitoring. Of those requiring additional evaluation, 5 (1%) patients warranted further evaluation before discharge. CONCLUSIONS: Nearly one-third of patients had at least one radiographic finding unrelated to their injury. Of these, more than two-thirds did not require additional evaluation, but nearly one third of patients required some form of further work-up. PMID- 28987313 TI - Pneumocephalus and Sixth Nerve Palsy after Epidural Steroid Injection: Case Report and Review of the Literature. AB - BACKGROUND: Pneumocephalus has been described as an unintended outcome after epidural injections. However, oculomotor palsy from pneumocephalus after epidural injection is very rare. CASE REPORT: We report a case of pneumocephalus-induced sixth nerve palsies and diplopia in an 87-year-old woman after epidural steroid injection. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Pneumocephalus induced oculomotor palsy is a rare complication after epidural injection, a commonly performed medical procedure. Knowledge of this presentation will help emergency physicians distinguish between this entity and other causes of neurologic deficits. PMID- 28987314 TI - Use of Prophylactic Ondansetron with Intravenous Opioids in Emergency Department Patients: A Prospective Observational Pilot Study. AB - BACKGROUND: The current literature suggests that the prophylactic use of antiemetics is ineffective at preventing nausea or vomiting caused by opioids in the emergency department (ED). While there is no data evaluating ondansetron's efficacy for preventing opioid-induced nausea and vomiting, this practice remains common despite a lack of supporting evidence. OBJECTIVES: This study aimed to identify if prophylactic ondansetron administered with intravenous (IV) opioids prevents opioid-induced nausea or vomiting. METHODS: This prospective observational study was conducted in the ED at two academic medical institutions. Patients were eligible for enrollment if they were prescribed an IV opioid with or without IV ondansetron and absence of baseline nausea. Patients' level of nausea was evaluated at baseline, 5 min, and 30 min after an IV opioid was administered and then observed for 2 hours. RESULTS: One hundred thirty-three patients were enrolled, with 90% of patients presenting with a chief complaint of pain. Sixty-four (48.1%) patients received an IV opioid alone and 69 (51.9%) patients received both IV ondansetron and an IV opioid. Twenty-three (17.3%) patients developed nausea caused by opioid administration. One (0.75%) patient had an emetic event and 3 (2.3%) patients required rescue antiemetics during their observation period. Rate of nausea was similar between treatment groups 5 min after the opioid was administered (p = 0.153). There was no statistical difference in emesis, rescue medication requirements, or nausea severity between treatment groups. CONCLUSION: Our trial found that ondansetron did not appear to be effective at preventing opioid-induced nausea or vomiting. These findings and previous literature suggest prophylactic ondansetron should not be given to ED patients who are receiving IV opioids. PMID- 28987315 TI - Abscess of the Base of Tongue and Epiglottis. PMID- 28987316 TI - Bypass for symptomatic in-stent carotid restenosis. AB - BACKGROUND: To evaluate early and long-term outcomes of symptomatic patients treated for in-stent carotid restenosis (ISR) with carotid bypass (CB). METHODS: Data were retrospectively collected from a prospectively compiled database on patients treated with CB in two high-volume Italian centers between 2008 and 2016, for symptomatic high-grade ISR after CAS. After carotid endarterectomy and stent removal, a greater saphenous vein (GSV) was preferentially employed as the graft; when the GSV was not accessible, a 6mm polytetrafluoroethylene (PTFE) graft was implanted. Standard follow-up protocol included clinical examinations, duplex scans (DUS) and computed tomographic angiography. Measures considered for analysis were perioperative (30-day) and long-term occurrence of new ipsilateral cerebral events, neurological deficits, death from all causes, and needs for reintervention. In addition, peripheral nerve palsy, cervical hematomas, and other local complications after surgery were noted. RESULTS: The population of the study comprised 13 patients (11 men and two women; median age was 66.5years (range 56-88)). Mean times from index CAS to stent explantation were 38.9+/ 18.2months. GSV grafts were used in seven cases (53.8%) and PTFE grafts in the remaining six (46.2%) cases. Intraoperative neurological complications rate was null. One patient presented a transient dysphagia. At 30-day, no new neurological complications, reinterventions or deaths occurred. At mean follow-up of 41.2+/ 18.2months, three patients died in absence of further neurological events. None of the CB patients required reintervention. CONCLUSIONS: In our experience, CB offers satisfactory results in patients treated for symptomatic ISR with an acceptable risk of cranial nerve injury. PMID- 28987317 TI - Nationwide survival after inhospital cardiac arrest before and after 2010 cardiopulmonary resuscitation guidelines: 2007-2014. AB - BACKGROUND: American Heart Association has been revising the cardiopulmonary resuscitation (CPR) guidelines quinquennially. We sought to study the influence of 2010 CPR guidelines on nationwide survival after inhospital cardiac arrest. METHODS: Healthcare Utilization Project's National Inpatient Sample 20007-2014, was used to identify 799,741 adults aged >=15years, who underwent inhospital CPR. We compared inhospital survival trends during period before (2007-2010) and after (2011-2014) American Heart Association 2010 CPR guidelines. RESULTS: Mean age of the study population was 66.5years. Females constituted 44% of the study cohort. There was a significant improvement in survival after inhospital CPR from 24.1% in 2007 to 31.1% in 2014 (Ptrend<0.001). However, we did not find any statistically significant improvement in inhospital survival after CPR, in the study period after 2010 AHA CPR guidelines in comparison to study period before the guidelines. CONCLUSIONS: We noted a significant improvement in inhospital survival rate after CPR from 2007 through 2014 in the United States, though there was no statistically significant improvement in survival trends after 2010 CPR guidelines during period 2011-2014, in comparison to period 2007-2010. PMID- 28987318 TI - Co-instillation of nano-solid magnesium hydroxide enhances corneal permeability of dissolved timolol. AB - We prepared magnesium hydroxide (MH) nanoparticles by a bead mill method, and investigated whether the co-instillation of MH nanoparticles improves the low transcorneal penetration of water-soluble drugs, such as the anti-glaucoma eye drug timolol maleate (TM). MH particle size was decreased by the bead mill treatment to a mean particle size of 71 nm. In addition, the MH nanoparticles were highly stable. Next, we demonstrated the effect of MH nanoparticles on the corneal surface. MH shows only slight solubility in lacrimal fluid, and the instillation of MH nanoparticles for 14 days did not affect the behavior (balance of secretion and excretion) of the lacrimal fluid in rabbit corneas. Moreover, there was no observable corneal toxicity of MH nanoparticles, and treatment with MH nanoparticles enhanced the intercellular space ratio in the eyes of rats. MH alone did not permeate into the cornea; however, the co-instillation of MH nanoparticles and dissolved TM (nMTFC) enhanced the corneal penetration of TM. In addition, the intraocular pressure (IOP)-reducing effect of nMTFC was significantly higher than those of the TM solution or the co-instillation of MH microparticles and TM. In conclusion, we found that MH nanoparticles enhance the corneal penetration of dissolved TM with no observable corneal stimulation or obstruction of the nasolacrimal duct by the MH nanoparticles. It is possible that the co-instillation of MH nanoparticles may provide a useful way to improve the bioavailability of water-soluble drugs in the ophthalmic field. These findings provide significant information that can be used to design further studies aimed at developing anti-glaucoma eye drugs. PMID- 28987319 TI - Mitochondria, telomeres and cell senescence: Implications for lung ageing and disease. AB - Cellular senescence, the irreversible loss of replicative capacity in somatic cells, plays a causal role in the development of age-related pathology and in a number of age-related chronic inflammatory diseases. The ageing lung is marked by an increasing number of senescent cells, and evidence is mounting that senescence may directly contribute to a number of age-related respiratory diseases, including chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). Telomere dysfunction and alterations in mitochondrial homeostasis frequently occur in cellular senescence and are important to the development of the often detrimental senescence-associated secretory phenotype (SASP). The roles of telomeres, the mitochondria and cellular senescence in lung ageing and disease are discussed. Therapeutic interventions targeting cellular senescence are considered for delaying or potentially reversing age-related respiratory disease. PMID- 28987320 TI - Lung development, regeneration and plasticity: From disease physiopathology to drug design using induced pluripotent stem cells. AB - Lungs have a complex structure composed of different cell types that form approximately 17 million airway branches of gas-delivering bronchioles connected to 500 million gas-exchanging alveoli. Airways and alveoli are lined by epithelial cells that display a low rate of turnover at steady-state, but can regenerate the epithelium in response to injuries. Here, we review the key points of lung development, homeostasis and epithelial cell plasticity in response to injury and disease, because this knowledge is required to develop new lung disease treatments. Of note, canonical signaling pathways that are essential for proper lung development during embryogenesis are also involved in the pathophysiology of most chronic airway diseases. Moreover, the perfect control of these interconnected pathways is needed for the successful differentiation of induced pluripotent stem cells (iPSC) into lung cells. Indeed, differentiation of iPSC into airway epithelium and alveoli is based on the use of biomimetics of normal embryonic and fetal lung development. In vitro iPSC-based models of lung diseases can help us to better understand the impaired lung repair capacity and to identify new therapeutic targets and new approaches, such as lung cell therapy. PMID- 28987322 TI - An insight into the complex roles of metallothioneins in malignant diseases with emphasis on (sub)isoforms/isoforms and epigenetics phenomena. AB - Metallothioneins (MTs) belong to a group of small cysteine-rich proteins that are ubiquitous throughout all kingdoms. The main function of MTs is scavenging of free radicals and detoxification and homeostating of heavy metals. In humans, 16 genes localized on chromosome 16 have been identified to encode four MT isoforms labelled by numbers (MT-1-MT-4). MT-2, MT-3 and MT-4 proteins are encoded by a single gene. MT-1 comprises many (sub)isoforms. The known active MT-1 genes are MT-1A, -1B, -1E, -1F, -1G, -1H, -1M and -1X. The rest of the MT-1 genes (MT-1C, 1D, -1I, -1J and -1L) are pseudogenes. The expression and localization of individual MT (sub)isoforms and pseudogenes vary at intra-cellular level and in individual tissues. Changes in MT expression are associated with the process of carcinogenesis of various types of human malignancies, or with a more aggressive phenotype and therapeutic resistance. Hence, MT (sub)isoform profiling status could be utilized for diagnostics and therapy of tumour diseases. This review aims on a comprehensive summary of methods for analysis of MTs at (sub)isoforms levels, their expression in single tumour diseases and strategies how this knowledge can be utilized in anticancer therapy. PMID- 28987323 TI - The longevity gene INDY (I'm Not Dead Yet) in metabolic control: Potential as pharmacological target. AB - The regulation of metabolic processes by the Indy (I'm Not Dead Yet) (SLC13A5/NaCT) gene was revealed through studies in Drosophila melanogaster and Caenorhabditis elegans. Reducing the expression of Indy in these species extended their life span by a mechanism resembling caloric restriction, without reducing food intake. In D. melanogaster, mutating the Indy gene reduced body fat content, insulin-like proteins and reactive oxygen species production. Subsequent studies indicated that Indy encodes a citrate transporter located on the cell plasma membrane. The transporter is highly expressed in the mammalian liver. We generated a mammalian knock out model deleting the mammalian homolog mIndy (SLC13A5). The knock out animals were protected from HFD induced obesity, fatty liver and insulin resistance. Moreover, we have shown that inducible and liver selective knock down of mIndy protects against the development of fatty liver and insulin resistance and that obese humans with type 2 diabetes and non-alcoholic fatty liver disease have increased levels of mIndy. Therefore, the transporter mINDY (NaCT) has been proposed to be an 'ideal target for the treatment of metabolic disease'. A small molecule inhibitor of the mINDY transporter has been generated, normalizing glucose levels and reducing fatty liver in a model of diet induced obese mice. Taken together, studies from lower organisms, mammals and humans suggest that mINDY (NaCT) is an attractive target for the treatment of metabolic disease. PMID- 28987321 TI - The role of human dopamine transporter in NeuroAIDS. AB - HIV-associated neurocognitive disorder (HAND) remains highly prevalent in HIV infected individuals and represents a special group of neuropathological disorders, which are associated with HIV-1 viral proteins, such as transactivator of transcription (Tat) protein. Cocaine abuse increases the incidence of HAND and exacerbates its severity by enhancing viral replication. Perturbation of dopaminergic transmission has been implicated as a risk factor of HAND. The presynaptic dopamine (DA) transporter (DAT) is essential for DA homeostasis and dopaminergic modulation of the brain function including cognition. Tat and cocaine synergistically elevate synaptic DA levels by acting directly on human DAT (hDAT), ultimately leading to dysregulation of DA transmission. Through integrated computational modeling and experimental validation, key residues have been identified in hDAT that play a critical role in Tat-induced inhibition of DAT and induce transporter conformational transitions. This review presents current information regarding neurological changes in DAT-mediated dopaminergic system associated with HIV infection, DAT-mediated adaptive responses to Tat as well as allosteric modulatory effects of novel compounds on hDAT. Understanding the molecular mechanisms by which Tat induces DAT-mediated dysregulation of DA system is of great clinical interest for identifying new targets for an early therapeutic intervention for HAND. PMID- 28987325 TI - Anti-tumor compound RY10-4 suppresses multidrug resistance in MCF-7/ADR cells by inhibiting PI3K/Akt/NF-kappaB signaling. AB - RY10-4, an anti-tumor agent, exerts cytotoxicity to various human cancer cell lines. However, few studies reported the effect of combined application of RY10-4 and chemotherapeutic drugs against cancer cells with multidrug resistance (MDR). In this study, P-glycoprotein (P-gp), which is reported to mediate MDR to anti cancer drugs, was proved to be overexpressed in the adriamycin (ADR)-resistant human breast cancer cells, namely MCF-7/ADR cells. Furthermore, RY10-4 application resulted in a downregulation of P-gp in MCF-7/ADR cells, thus leading to higher chemosensitivity to ADR. Our study further demonstrated that the MDR phenomenon was under the control of the PI3K/Akt/NF-kappaB pathway, which was suppressed by RY10-4, leading to MDR reversal effects in MCF-7/ADR cells. In vivo, MCF-7/ADR cells were effectively suppressed by the combined ADR/RY10-4 treatment compared with the ADR-alone treatment. Taken together, these results demonstrated that RY10-4 reverses the MDR phenotype in MCF-7/ADR cells by suppressing the PI3K/Akt/NF-kappaB pathway. PMID- 28987326 TI - Synthesis, characterization and biological studies of a cobalt(III) complex of sulfathiazole. AB - The emergence of old and new antibiotic resistance created in the last decades revealed a substantial medical need for new classes of antimicrobial agents. The antimicrobial activity of sulfa drugs is often enhanced by complexation with metal ions, which is in concordance with the well-known importance of metal ions in biological systems. Besides, sulfonamides and its derivatives constitute an important class of drugs, with several types of pharmacological agents possessing antibacterial, anti-carbonic anhydrase, diuretic, hypoglycemic, antithyroid, antiviral and anticancer activities, among others. The purpose of this work has been the obtainment, characterization and determination of biological properties (antibacterial, antifungal, mutagenicity and phytotoxicity) of a new Co(III) sulfathiazole complex: Costz, besides of its interaction with bovine serum albumin (BSA). The reaction between sodium sulfathiazole (Nastz) and cobalt(II) chloride in the presence of H2O2 leads to a brown solid, [CoIII(stz)2OH(H2O)3], (Costz). The structure of this compound has been examined by means of elemental analyses, FT-IR, 1H NMR, UV-Visible spectrometric methods and thermal studies. The Co(III) ion, which exhibits a distorted octahedral environment, could coordinate with the N thiazolic atom of sulfathiazolate. The complex quenched partially the native fluorescence of bovine serum albumin (BSA), suggesting a specific interaction with the protein. The Costz complex showed, in vitro, a moderate antifungal activity against Aspergillus fumigatus and A. flavus. As antibacterial, Costz displayed, in vitro, enhanced activity respective to the ligand against Pseudomonas aeruginosa. Costz did not show mutagenic properties with the Ames test. In the Allium cepa test the complex showed cytotoxic properties but not genotoxic ones. These results may be auspicious, however, further biological studies are needed to consider the complex Costz as a possible drug in the future. PMID- 28987328 TI - The presence of oleate stabilized ZnO nanoparticles (NPs) and reduced the toxicity of aged NPs to Caco-2 and HepG2 cells. AB - The presence of food components may alter the colloidal aspects and toxicity of nanoparticles (NPs). In this study, the toxicity of ZnO NPs to Caco-2 and HepG2 cells was assessed, with the emphasis on the interactions between ZnO NPs and oleate (OA). The presence of OA increased UV-Vis spectra and hydrodynamic sizes, decreased Zeta potential, and markedly reduced the release of Zn ions from the dissolution of ZnO NPs, which combined indicated that OA could coat ZnO NPs and stabilize ZnO NPs. Exposure to ZnO NPs significantly induced cytotoxicity to Caco 2 and HepG2 cells, associated with increased intracellular Zn ions but not superoxide. When OA was added to the freshly prepared ZnO NP suspensions, the cytotoxicity, intracellular Zn ions and superoxide induced by ZnO NPs were not significantly affected. However, when ZnO NPs were aged for 24 h with the presence of OA, the cytotoxicity of ZnO NPs to Caco-2 and HepG2 cells was significantly reduced, associated with a reduction of intracellular Zn ions. The results from this study suggested that the presence of OA could increase colloidal stability of ZnO NPs and consequently reduce the toxicity of ZnO NPs after aging associated with reduced accumulation of intracellular Zn ions. PMID- 28987327 TI - The implication of p66shc in oxidative stress induced by deltamethrin. AB - Deltamethrin (DLT) is effective against a broad spectrum of insects. Exposure to DLT has been demonstrated to cause oxidative stress. However, the mechanism of oxidative stress induced by DLT is little known. Groups of rats were gavaged with DLT once daily for 7 days at six dosages: 0, 2, 5, 10, 20, 40 mg/kg. The intensity of neurotoxicity and liver dysfunction caused by DLT were significantly increased in a dose-dependent manner. We found that DLT caused the increase of cytosolic superoxide in tissues. Western blot analysis showed that both the expression of p66shc and Ser36 phosphorylated p66shc, which were involved in ROS generation, were increased in tissues treated with DLT. Further investigation showed that DLT treatment resulted in the increase of intracellular ROS accompanied with elevated p66shc expression in different cell lines. And treatment of cells with DLT induced p66shc phosphorylation at Ser36 and the translocation of p66shc from cytoplasm to mitochondria. Moreover, the overexpression of wildtype p66shc caused the increase of DLT-mediated ROS level in SH-SY5Y cells, but cells overexpressing p66shcSer36Ala mutant plasmid had the opposite effect. And p66shc suppression by siRNA blunted DLT-mediated ROS generation. Taken together, our findings indicated p66shc mediated DLT-induced oxidative stress, which may be partly responsible for toxic effects. PMID- 28987324 TI - Toll-like receptors and their role in persistent pain. AB - One of the fundamental mechanisms whereby the innate immune system coordinates inflammatory signal transduction is through Toll-like receptors (TLRs), which function to protect and defend the host organism by initiating inflammatory signaling cascades in response to tissue damage or injury. TLRs are positioned at the neuroimmune interface, and accumulating evidence suggests that the inflammatory consequences of TLR activation on glia (including microglia and astrocytes), sensory neurons, and other cell types can influence nociceptive processing and lead to states of exaggerated and unresolved pain. In this review, we summarize our current understanding of how different TLRs and their accessory or adaptor molecules can contribute to the development and maintenance of persistent pain. The challenges and opportunities of targeting TLRs for new treatment strategies against chronic pain are discussed, including the therapeutic context of TLR-mediated signaling in opioid analgesia and chemotherapy-induced pain. Considering the prevalence of persistent pain and the insufficient efficacy and safety of current treatment options, a deeper understanding of Toll-like receptors holds the promise of novel therapies for managing pathological pain. PMID- 28987329 TI - Effects of a new synthetic zerumbone pendant derivative (ZPD) on apoptosis induction and anti-migratory effects in human cervical cancer cells. AB - A newly synthesised zerumbone pendant derivative (ZPD) was studied in human cervical cancer cells (HeLa) for its anticancer properties. ZPD significantly inhibited the growth of human cervical cancer cells with a GI50 value of 6.35 +/- 1.30 MUM, which also induced morphological changes and apoptosis in a dose dependent manner. Our data indicated that ZPD actively encouraged programmed cell death in HeLa cells which were confirmed by DNA fragmentation, phosphatidylserine translocation, increased activity of caspase 3, upregulation of the expression of the pro-apoptotic protein Bax, cleaved PARP, cleaved caspase 3 and downregulation of anti-apoptotic protein Bcl-2. ZPD also inhibited cell migration of HeLa cells, decreasing the production of MMP-2,-9 and downregulation of expression of MMPs and pro-angiogenic factor VEGF. Also it is nontoxic to normal rat cardiac myoblasts. Overall, ZPD is a promising candidate for inducing cytotoxicity, apoptosis and anti-migratory effects in cervical cancer cells. PMID- 28987330 TI - Physical activity and screen-based recreation: Prevalences and trends over time among adolescents and barriers to recommended engagement. AB - Adolescence is a critical time for disengagement from physical activity making young people a priority group for interventions. To determine whether existing initiatives are working in this population segment and help inform future programs, the present study sought to (i) examine prevalences and trends in physical activity and screen-based recreation among Australian adolescents and (ii) identify the barriers to adolescents meeting recommended guidelines. Two cross-sectional representative samples of Western Australian secondary school students aged 12 to 17years were surveyed in 2009-2010 (n=1505) and 2012-2013 (n=1406). Around a quarter (24%) of boys and just 9% of girls reported engaging in the recommended 60min of physical activity per day in 2012-2013. A minority (13% of boys, 17% of girls) adhered to guidelines for time spent engaging in screen-based recreation (<=2h of electronic media use for entertainment). These findings were comparable to 2009-2010 prevalence levels. Multivariable logistic regression analyses conducted on data from the most recent wave found individual level barriers to be significantly associated with lower odds of meeting physical activity guidelines in both boys (Adj. OR=0.52, 95% CI=0.38, 0.72) and girls (Adj. OR=0.41, 95% CI=0.25, 0.66). The consistently high proportion of adolescents not meeting physical activity recommendations over time suggests that current efforts to increase physical activity may be failing to have an impact on population-level trends in compliance. While initiatives to improve the built environment may reduce barriers at the environmental level, these initiatives risk having little impact on physical activity if individual level barriers remain unaddressed. PMID- 28987331 TI - State-level educational disparities in mortality in the United States, 2010-2014. AB - The present study examined educational disparities in mortality for 49 states and the District of Columbia in the United States based on the 2010-2014 national mortality data. A total of 3,165,762 deaths at ages 25-74years were included in analysis. Absolute and relative disparities were estimated as Relative Index of Inequality (RII) and Slope Index of Inequality (SII), respectively, based on age standardized death rates by education, race/ethnicity sex, and state. We found that educational disparities in mortality existed in every US state with varying magnitude across states and by sex. The disparities were generally larger in men than in women on both absolute and relative scales. Across states, for all races combined, the RII varied in the range of 4.2 to 14.9 in men and 3.2 to 10.1 in women; the SII (1/100,000 persons) ranged from 934.0 to 1633.4 in men and from 333.7 to 672.5 in women. Hispanic origin seems to alter the pattern of educational disparities by state. In non-Hispanic whites, some Midwest states had the smallest disparities on both relative and absolute scales. Maryland, Virginia, and Massachusetts had a large relative disparity but a moderate absolute disparity. In general, southern states had a large absolute disparity but a moderate relative disparity. There was a strong correlation (0.66; 95% CI, 0.46-0.79) between educational disparities in mortality and disparities in combined major risk factors (smoking, obesity, and hypertension) by state. These findings call for tailored interventions among socially disadvantaged populations, especially in high disparity states and among young adults. PMID- 28987332 TI - Disparities in cancer screening by occupational characteristics. AB - Cancer screening patterns according to occupation characteristics in the United States are not well known, but could be used to help inform cancer control efforts. We examined cervical (CC), breast (BC) and colorectal cancer (CRC) screening prevalence and prevalence ratios (PR) by occupational characteristics in 2010, 2013 and 2015 National Health Interview Surveys (NHIS) among eligible US workers (CC women 21-65years; n=20,997), (BC women >=40years; n=14,258) and (CRC men and women >=50years; n=17,333). Cervical, breast and colorectal cancer screening prevalence among US workers was 84.0%, 68.9%, and 56.8%, respectively. Unadjusted prevalence ratios for cervical (PR=0.92, 95%CI 0.90, 0.94), breast (PR=0.86, 95%CI 0.83, 0.90) and colorectal cancer screening (PR=0.83, 95%CI 0.80, 0.87) were lower among workers in small (<25 employees) compared to large organizations (>=500 employees). People in food service, construction, production, and sales occupations were 13-26%, 17-28% and 9-30% less likely to be up to date with cervical, breast, and colorectal cancer screening, respectively, compared to healthcare professionals. Adjustment for socioeconomic factors and insurance status eliminated most associations. Disparities in cancer screening by occupational characteristics were mostly attributed to lower socioeconomic status and lack of insurance. These findings underscore the need for innovative public health strategies to improve cancer screening in vulnerable populations. PMID- 28987333 TI - Age of onset for physical and sexual teen dating violence perpetration: A longitudinal investigation. AB - Teen dating violence (TDV) is a serious and prevalent public health problem. TDV is associated with a number of negative health consequences for victims and predicts violence in adult relationships. Thus, efforts should be devoted to the primary prevention of TDV. However, only a few studies have examined when the risk for the first occurrence of TDV is greatest. Continued research in this area would inform the timing of, as well as developmentally appropriate strategies for, TDV primary prevention efforts. The current study examined at which age(s) the risk for TDV perpetration onset was greatest. Utilizing a panel-based design, a sample of racially/ethnically diverse high school students (N=872; 56% female) from the Southwestern United States completed self-report surveys on physical and sexual TDV perpetration annually for six years (2010 to 2016). Findings suggested that the physical TDV risk of onset was at or before ages 15 to 16 for females and at or before age 18 for males. For sexual TDV perpetration, risk was similar for males and females during adolescence, before uniquely increasing for males, and not females in emerging adulthood. Findings highlight the need for TDV primary prevention programs to be implemented early in high school, and potentially in middle school. PMID- 28987335 TI - Multimorbidity in Atlantic Canada and association with low levels of physical activity. AB - Owing to an aging population and medical advances, the anticipated growth and prevalence of multimorbidity has been recognized as a significant challenge and priority in health care settings. Although physical activity has been shown to play a vital role in the primary and secondary prevention of chronic disease, much less is known about the relationship between physical activity and multimorbidity. The objective of the present study was to examine the relationship between physical activity levels and multimorbidity in male and female adults after adjusting for key demographic, geographical, and lifestyle factors. The study drew data from a prospective cohort in Atlantic Canada (2009 2015). The sample included 18,709 participants between the ages of 35-69. Eighteen chronic diseases were identified. Physical activity levels were estimated based on the long form of the International Physical Activity Questionnaire. Using logistic regression analysis, we found that multimorbid individuals were significantly more likely to be physically inactive (OR=1.26; 95% CI 1.10, 1.44) after adjusting for key sociodemographic and lifestyle characteristics. Additional stratified analyses suggest that the magnitude of the effect between multimorbidity and physical activity was stronger for men (OR=1.41; 95% CI 1.12, 1.79) than women (OR=1.18; CI 1.00, 1.39) and those living in rural (OR=1.43; CI 1.10, 1.85) versus urban (OR=1.20; CI 1.02, 141) areas. Given the generally low levels of physical activity across populations and a growing prevalence of multimorbidity, there is a need for a prospective study to explore causal associations between physical activity, multimorbidity, and health outcomes. PMID- 28987334 TI - Cost effectiveness and return on investment of a scalable community weight loss intervention. AB - This study assessed the lifetime health and economic consequences of an efficacious scalable community weight loss program for overweight and obese adults. We applied a state-transition Markov model to project lifetime economic outcome (US dollar) and the degree of disease averted as a result of a weight loss intervention, compared with no intervention, from a payer perspective. Effect sizes of the intervention on weight loss, by sex, race and ethnicity, and body mass index (BMI) of participants, were derived from a 12-month community program. Relative risk of diseases across BMI levels and other parameters were informed by the literature. A return on investment (ROI) analysis was conducted to present the overall cost-benefit of the program. Simulation results showed that among 33,656 participants and at a cost of $2.88 million, the program was predicted to avert (with a corresponding estimated medical costs saved of) 78 cases of coronary heart disease ($28 million), 9 cases of strokes ($971,832), 92 cases of type 2 diabetes ($24 million), 1 case of colorectal cancer ($357,022), and 3 cases of breast cancer ($483,259) over the participant lifetime. The estimated medical costs saved per participant was $1403 ($1077 of African American men and $1532 of Hispanic men), and the ROI was $16.7 ($12.8 for African American men and $18.3 for Hispanic men) for every $1 invested. We concluded that a scalable efficacious community weight loss program provides a cost-effective approach with significant ROI, which will assist informed decisions for future adoption and dissemination. PMID- 28987336 TI - Physical activity trajectories during midlife and subsequent risk of physical functioning decline in late mid-life: The Study of Women's Health Across the Nation (SWAN). AB - The purpose of this study was to examine the importance of midlife physical activity on physical functioning in later life. Data are from 1771 Study of Women's Health Across the Nation (SWAN) participants, aged 42-52 (46.4+/-2.7) years at baseline (1996-97). Latent class growth analysis was used to identify physical activity trajectory groups using reported sports and exercise index data collected at seven time-points from baseline to Visit 13 (2011-13); objective measures of physical functioning performance were collected at Visit 13. The sports and exercise index (henceforth: physical activity) is a measure of moderate to vigorous intensity physical activity during discretionary periods of the day. Multivariable linear regression analyses were used to model each continuous physical performance measure as a function of the physical activity trajectory class. Across midlife, five physical activity trajectory classes emerged, including: lowest (26.2% of participants), increasing (13.4%), decreasing (22.4%), middle (23.9%), and highest (14.1%) physical activity. After full adjustment, women included in the middle and highest physical activity groups demonstrated >=5% better physical functioning performance than those who maintained low physical activity levels (all comparisons; p<0.05). Statistically significant differences were also noted when physical activity trajectory groups were compared to the increasing physical activity group. Results from the current study support health promotion efforts targeting increased (or maintenance of) habitual physical activity in women during midlife to reduce future risk of functional limitations and disability. These findings have important public health and clinical relevance as future generations continue to transition into older adulthood. PMID- 28987337 TI - The differential impact of state tobacco control policies on cessation treatment utilization across established tobacco disparities groups. AB - Tobacco control policies are effective in promoting quit attempts and increase the likelihood that smokers use evidence-based cessation treatments (e.g., nicotine replacement therapies (NRT), non-NRT medications, behavioral treatment, and/or quitlines). However, what is less clear is how these policies might differentially impact different groups of smokers, perhaps in some cases even widening disparities in the use of evidence-based tobacco dependence treatments. This paper examined how different state-level tobacco control policies impact the use of evidence-based cessation treatments by race/ethnicity, gender, socio economic status (SES), age, and smoking history. Participants included 9110 adult smokers reporting a past-year quit attempt within the 2010-2011 Tobacco Use Supplement to the Current Population Survey. Lasso regression modeling was used to identify a subset of interactions between tobacco policies and individual smoker characteristics that predicted use of evidence-based cessation treatment. Significant interactions were fitted via participant-weighted generalized linear models to determine effect sizes and relations to each cessation treatment outcome. Results highlighted that various state level tobacco control policies differentially impacted the reported use of both prescription and non prescription stop smoking medications by race/ethnicity, age, and SES. The relationship between state level tobacco control policies and the use of behavioral treatments and quitlines did not differ by smoker characteristics. In sum, tobacco control policies differentially impact the use of FDA approved stop smoking medications across different race/ethnicity, age, and SES groups. Understanding such effects can help to target interventions to ensure equal access to evidence-based tobacco dependence treatments. PMID- 28987338 TI - Increasing colorectal cancer incidence trends among younger adults in Canada. AB - Recent analyses in the United States have shown an overall decrease in the incidence of colorectal cancer despite contrasting increases in younger age groups. We examined whether these cohort trends are occurring in Canada. Age specific trends in colon and rectal cancer incidence in Canada from the National Cancer Incidence Reporting System (1969-1992) and the Canadian Cancer Registry (1992-2012) were analyzed. We estimated annual percent changes (APC) with the Joinpoint Regression Program from the Surveillance Epidemiology, and End Results Program. Birth cohort effects were estimated using 5-year groups starting in 1888. Age-specific prevalence of class I, II and III obesity in Canada was examined from the National Population Health Survey (1994-2001) and the Canadian Community Health Survey (2001-2011). The reductions in CRC incidence among Canadians are limited to older populations. While reductions among younger age groups (20-29year olds (yo), 30-39yo and 40-50yo) were observed between 1969 and 1995, rates have returned to and surpassed historical levels (APCs 20-29yo colon cancer=6.24%, APCs 20-29yo rectal cancer=1.5%). Recent birth cohorts (1970-1990) have the highest incidence rate ratios ever recorded. Ecologic trends in obesity prevalence among these birth cohorts in Canada are suggestive of an impact on increasing incidence trends. Furthermore, obesity prevalence estimates suggest that these trends may continue to increase justifying further examination of the etiologic associations and biological impacts of excess adipose tissue among younger populations. While population-based screening of younger age groups deserves careful consideration, these concerning observed trends warrant public health action to address the growing obesity epidemic. PMID- 28987339 TI - Assessing the role of access and price on the consumption of fruits and vegetables across New York City using agent-based modeling. AB - Most residents in New York City (NYC) do not consume sufficient fruits and vegetables every day. Difficulties with access and high prices of fruits and vegetables in some neighborhoods contribute to different consumption patterns across NYC neighborhoods. We developed an agent-based model (ABM) to predict dietary behaviors of individuals at the borough and neighborhood levels. Model parameters were estimated from the 2014 NYC Community Health Survey, United States Census data, and the literature. We simulated six hypothetical interventions designed to improve access and reduce the price of fruits and vegetables. We found that all interventions would lead to increases in fruit and vegetable consumption but the results vary substantially across boroughs and neighborhoods. For example, a 10% increase in the number of fruit/vegetable vendors combined with a 10% decrease in the prices of fruits and vegetables would lead to a median increase of 2.28% (range: 0.65%-4.92%) in the consumption of fruits and vegetables, depending on neighborhood. We also found that the impact of increasing the number of vendors on fruit/vegetable consumption is more pronounced in unhealthier local food environments while the impact of reducing prices on fruits/vegetable consumption is more pronounced in neighborhoods with low levels of education. An agent-based model of dietary behaviors that takes into account neighborhood context has the potential to inform how fruit/vegetable access and pricing strategies may specifically work in tandem to increase the consumption of fruits and vegetables at the local level. PMID- 28987340 TI - Does your child's weight influence how you judge yourself as a parent? A cross sectional study to define and examine parental overvaluation of weight/shape. AB - Parents are integral stakeholders in children's health and development, and yet there is a dearth of research on parental attitudes and parents' personal weight and eating psychopathology, which have the potential to influence pediatric obesity and eating disorder treatments meaningfully. Overvaluation of weight/shape is a core concept in eating-disorder assessment and treatment defined as self-evaluation excessively based on weight/shape, which research has demonstrated to be clinically important psychopathology. A novel and related concept, parental overvaluation of weight/shape, could be defined as parents' self-evaluation unduly based on their child's weight/shape, yet this concept has not been studied and its clinical importance is unknown. The aim of this study was to examine the distinctiveness of parental overvaluation of weight/shape from personal overvaluation of weight/shape, and to examine associations of parental overvaluation with parents' psychopathology and children's weight and eating behaviors. The current study examined differences among parents with (n=134) and without (n=872) parental overvaluation using a cross-sectional design. Parental overvaluation was more common among parents with binge-eating disorder and bulimia than obesity and healthy-weight. Parental overvaluation was modestly associated with personal overvaluation. Parents with and without parental overvaluation differed on personal eating-disorder psychopathology and children's weight and eating behaviors. Importantly, differences remained after adjusting for personal overvaluation and child BMI. This study highlights a novel construct parental overvaluation-associated with, but distinct from, parental eating disorders and personal overvaluation. Parental overvaluation may warrant clinical attention among parents seeking pediatric obesity or eating-disorder treatment, or treatment for personal eating disorders. PMID- 28987341 TI - Economic evaluation of a group randomized controlled trial on healthy eating and physical activity in afterschool programs. AB - Limited information is available on the cost-effectiveness of interventions to achieve healthy eating and physical activity policies in afterschool programs (ASPs). The objective of this study is to present the costs associated with a comprehensive intervention in ASPs. Intervention delivery inputs (IDIs) associated with a group randomized delayed treatment controlled trial involving 20 ASPs serving >1700 children (5-12yrs) were catalogued prospectively across 2 years (2014-2015). IDIs, analyzed 2015, were expressed as increases in per-child per-week enrollment fees based on a 34-week school year in US$. Total IDIs for year-1 were $15,058 (+$0.58/child/week enrollment fee). In year-2, total costs were $13,828 (+$0.52/child/week) for the delayed group and $7916 (+$0.30/child/week) for the immediate group, respectively. Site leader and staff hourly wages represented 11-17% and 45-46% of initial training costs; travel and trainer wages represented 31-42% and 50-58% of booster costs. Overall, a 1% increase in boys and girls, separately, accumulating 30 mins/d of moderate-to vigorous physical activity ranged from $0.05 to $0.26/child/week, while a one-day increase in serving a fruit/vegetable or water, or not serving sugar-added foods/beverages ranged from $0.16 to $0.87/child/week. Costs associated with implementing the intervention were minimal. Additional efforts to reduce costs and improve intervention effectiveness are necessary. PMID- 28987342 TI - Where and when adolescents are physically active: Neighborhood environment and psychosocial correlates and their interactions. AB - Female adolescents are less active than male peers in certain contexts including the neighborhood. Adolescents' physical activity can be explained by interactions between environmental and psychosocial factors, but few studies have tested such interactions in relation to context-specific behaviors. This study tested interactions between neighborhood environmental and psychosocial factors in relation to adolescents' context-specific physical activity. Data were collected in 2009-11 from 910 adolescents and a parent/guardian residing in the Baltimore/Seattle regions. Measures included adolescent-reported neighborhood leisure-time physical activity (LTPA) and non-neighborhood LTPA, accelerometer based non-school moderate-to vigorous-physical activity (MVPA), psychosocial factors, and objective and parent-perceived neighborhood environmental factors. Gender-stratified mixed effects linear models tested associations of 6 environmental and 4 psychosocial factors and their interactions in relation to each physical activity outcome. The psychosocial factors had consistent associations with the physical activity outcomes but the environmental correlates were context-specific. Decisional balance (weighing of pros and cons of physical activity) moderated the association between recreation facility density and neighborhood LTPA among females, with a negative association only among those with high decisional balance (pros outweighed cons). Decisional balance also moderated associations of neighborhood walkability with non-school MVPA among females and non-neighborhood LTPA among males, with positive associations only among those with high decisional balance. Results support context-specific ecological models of physical activity. Targeting environmental factors that may promote opportunities for physical activity in specific contexts as well as adolescent decision-making may help promote their physical activity in those contexts, potentially leading to increased overall physical activity. PMID- 28987343 TI - Comparison of gene co-expression networks in Pseudomonas aeruginosa and Staphylococcus aureus reveals conservation in some aspects of virulence. AB - Pseudomonas aeruginosa and Staphylococcus aureus are two evolutionary distant bacterial species that are frequently isolated from persistent infections such as chronic infectious wounds and severe lung infections in cystic fibrosis patients. To the best of our knowledge no comprehensive genome scale co-expression study has been already conducted on these two species and in most cases only the expression of very few genes has been the subject of investigation. In this study, in order to investigate the level of expressional conservation between these two species, using heterogeneous gene expression datasets the weighted gene co-expression network analysis (WGCNA) approach was applied to study both single and cross species genome scale co-expression patterns of these two species. Single species co-expression network analysis revealed that in P. aeruginosa, genes involved in quorum sensing (QS), iron uptake, nitrate respiration and type III secretion systems and in S. aureus, genes associated with the regulation of carbon metabolism, fatty acid-phospholipids metabolism and proteolysis represent considerable co-expression across a variety of experimental conditions. Moreover, the comparison of gene co-expression networks between P. aeruginosa and S. aureus was led to the identification of four co-expressed gene modules in both species totally consisting of 318 genes. Several genes related to two component signal transduction systems, small colony variants (SCVs) morphotype and protein complexes were found in the detected modules. We believe that targeting the key players among the identified co-expressed orthologous genes will be a potential intervention strategy to control refractory co-infections caused by these two bacterial species. PMID- 28987344 TI - Uncharacterized ORF HUR1 influences the efficiency of non-homologous end-joining repair in Saccharomyces cerevisiae. AB - Non-Homologous End Joining (NHEJ) is a highly conserved pathway that repairs Double-Strand Breaks (DSBs) within DNA. Here we show that the deletion of yeast uncharacterized ORF HUR1, Hydroxyurea Resistance1 affects the efficiency of NHEJ. Our findings are supported by Protein-Protein Interaction (PPI), genetic interaction and drug sensitivity analyses. To assess the activity of HUR1 in DSB repair, we deleted its non-overlapping region with PMR1, referred to as HUR1-A. We observed that similar to deletion of TPK1 and NEJ1, and unlike YKU70 (important for NHEJ of DNA with overhang and not blunt end), deletion of HUR1-A reduced the efficiency of NHEJ in both overhang and blunt end plasmid repair assays. Similarly, a chromosomal repair assay showed a reduction for repair efficiency when HUR1-A was deleted. In agreement with a functional connection for Hur1p with Tpk1p and NEJ1p, double mutant strains Deltahur1-A/Deltatpk1, and Deltahur1-A/Deltanej1 showed the same reduction in the efficiency of plasmid repair, compared to both single deletion strains. Also, using a Homologous Recombination (HR) specific plasmid-based DSB repair assay we observed that deletion of HUR1-A influenced the efficiency of HR repair, suggesting that HUR1 might also play additional roles in other DNA repair pathways. PMID- 28987345 TI - LncRNA-LINC00460 facilitates nasopharyngeal carcinoma tumorigenesis through sponging miR-149-5p to up-regulate IL6. AB - Long non-coding RNAs (lncRNAs) have played crucial roles in various cancers, including nasopharyngeal carcinoma (NPC). In our study, we focused on the biological function and clinical significance of lncRNA LINC00460 in NPC. It was indicated that LINC00460 was markedly increased in NPC tissues and cells compared to their corresponding controls. Silencing LINC00460 was able to suppress NPC cell growth in vitro while overexpressing LINC00460 reversed this process. Moreover, in vivo tumor xenografts were established using CNE-1/SUNE-1 cells to detect the function of LINC00460 in NSCLC tumorigenesis. Rescue assay was performed to further confirm that LINC00460 contributed to the progression of NPC through regulating miR-149-5p/IL6 signal pathway. In conclusion, we have uncovered that LINC00460 could be regarded as a novel prognostic biomarker and therapeutic target in NPC diagnosis and treatment. PMID- 28987346 TI - Over-expression of Oryza sativa Xrn4 confers plant resistance to virus infection. AB - Plant Xrn4 is a cytoplasmic 5' to 3' exoribonuclease that is reported to play an antiviral role during viral infection as demonstrated by experiments using the Xrn4s of Nicotiana benthamiana and Arabidopsis thaliana. Meanwhile, little is known about the anti-viral activity of Xrn4 from other plants. Here, we cloned the cytoplasmic Xrn4 gene of Oryza sativa (OsXrn4), and demonstrated that its over-expression elevated the 5'-3' exoribonuclease activity in rice plants and conferred resistance to rice stripe virus, a negative-sense RNA virus causing serious losses in East Asia. The accumulation of viral RNAs was also decreased. Moreover, the ectopic expression of OsXrn4 in N. benthamiana also conferred plant resistance to tobacco mosaic virus infection. These results show that the monocotyledonous plant cytoplasmic Xrn4 also has an antiviral role and thus provides a strategy for producing transgenic plants resistant to viral infection. PMID- 28987347 TI - Association study of apoptosis gene polymorphisms in mitochondrial diabetes: A potential role in the pathogenicity of MD. AB - Mitochondrial diabetes (MD) is a heterogeneous disorder characterized by a chronic hyperglycemia and is maternally transmitted. Syndromic MD is a subgroup of MD including diabetic microangiopathy and macroangiopathy, in addition to extrapancreatic disorder. MD is caused by genetic mutations and deletions affecting mitochondrial DNA. This mitochondrial damage initiates apoptosis. In this study, we hypothesized that functional polymorphisms in genes involved in apoptotic pathway could be associated with the development of apoptosis in MD disease and increased its risk. Detection of apoptosis was confirmed on muscle biopsies taken from MD patients using the TUNEL method and the Cytochrome c protein expression level. We genotyped then 11 published SNPs from intrinsic and extrinsic apoptotic pathway and assessed the signification of these polymorphisms in 43 MD patients and 100 healthy controls. We found 10 selected polymorphisms (p53 (rs1042522 and rs17878362), BCL2 (rs2279115), BAX (rs1805419), BAK1 (rs210132 and rs2227925), CASP3 (rs1405937), CASP7 (rs2227310), CASP8 (rs1045485) and CASP10 (rs13006529)) with a potential apoptosis effect in MD patients compared to control population. Specifically, SNPs involved in the intrinsic pathway (p53, BCL2, BAK1 and CASP3) presented the highest risk of apoptosis. Our result proved that apoptosis initiated by mtDNA mutations, can be emphasized by a functional apoptotic polymorphisms associated with high expression of cytochrome c protein and more myofibers with apoptosis in syndromic MD subgroup compared with non-syndromic MD subgroup. PMID- 28987348 TI - Application of novel Ni(II) complex and ZrO2 nanoparticle as mediators for electrocatalytic determination of N-acetylcysteine in drug samples. AB - The electrooxidation of N-acetylcysteine (N-AC) was studied by a novel Ni(II) complex modified ZrO2 nanoparticle carbon paste electrode [Ni(II)/ZrO2/NPs/CPE] using voltammetric methods. The results showed that Ni(II)/ZrO2/NPs/CPE had high electrocatalytic activity for the electrooxidation of N-AC in aqueous buffer solution (pH = 7.0). The electrocatalytic oxidation peak currents increase linearly with N-AC concentrations over the concentration ranges of 0.05-600MUM using square wave voltammetric methods. The detection limit for N-AC was equal to 0.009MUM. The catalytic reaction rate constant, kh, was calculated (7.01 * 102 M 1 s-1) using the chronoamperometry method. Finally, Ni(II)/ZrO2/NPs/CPE was also examined as an ultrasensitive electrochemical sensor for the determination of N AC in real samples such as tablet and urine. PMID- 28987349 TI - Corrigendum to "High-throughput liquid chromatography tandem mass spectrometry method for simultaneous determination of fampridine, paroxetine, and quinidine in rat plasma: Application to in vivo perfusion study" [J Food Drug Anal 24 (2016) 866-875]. PMID- 28987350 TI - Identification of cow milk in goat milk by nonlinear chemical fingerprint technique. AB - The objective of this paper was to develop a nonlinear chemical fingerprint technique for identifying and detecting adulteration of goat milk with cow milk. In this study, by taking the Belousov-Zhabotinsky oscillatory chemical reaction using acetone and substrates in goat milk or cow milk as main dissipative substances, when the same dosage of goat milk and cow milk was introduced to the "H+ + Mn2+ + BrO3- + acetone" oscillating system respectively, nonlinear chemical fingerprints were obtained for goat milk and cow milk from the same origin. The results showed that inductive time value and the content of cow milk in goat milk had a linear relationship in the range of 0-100% and the corresponding regression coefficient was 0.9991. A detection limit of 0.0107 g/g was obtained, and the content of cow milk in mixed milk was calculated. The proposed method in this study was simple, economical and effective. In addition, the method did not need the pretreatment and separation of samples for identifying and evaluating cow milk adulteration in goat milk. PMID- 28987351 TI - Effects of electrolysis time and electric potential on chlorine generation of electrolyzed deep ocean water. AB - Electrolyzed water is a sustainable disinfectant, which can comply with food safety regulations and is environmentally friendly. A two-factor central composite design was adopted for studying the effects of electrolysis time and electric potential on the chlorine generation efficiency of electrolyzed deep ocean water (DOW). DOW was electrolyzed in a glass electrolyzing cell equipped with platinum-plated titanium anode and cathode. The results showed that chlorine concentration reached maximal level in the batch process. Prolonged electrolysis reduced chlorine concentration in the electrolyte and was detrimental to electrolysis efficiency, especially under high electric potential conditions. Therefore, the optimal choice of electrolysis time depends on the electrolyzable chloride in DOW and cell potential adopted for electrolysis. The higher the electric potential, the faster the chlorine level reaches its maximum, but the lower the electric efficiency will be. PMID- 28987352 TI - Optimization conditions for extracting polysaccharide from Angelica sinensis and its antioxidant activities. AB - In this study, polysaccharides from Angelica sinensis were extracted using the ultrasound-assisted extraction method. Based on the results of single factor experiments and orthogonal tests, three independent variables-water/raw material ratio, ultrasound time, and ultrasound power-were selected for investigation. Then, we used response surface methodology to optimize the extraction conditions. The experimental data were fitted to a quadratic equation using multiple regression analysis, and the optimal conditions were as follows: water/raw material ratio, 43.31 mL/g; ultrasonic time, 28.06 minutes; power, 396.83 W. Under such conditions, the polysaccharide yield was 21.89+/-0.21%, which was well matched with the predicted yield. In vitro assays, scavenging activity of superoxide anion radicals, hydroxyl radicals, and 2,2-diphenyl-1-picry-hydrazyl radical showed that polysaccharides had certain antioxidant activities and that hydroxyl radicals have a remarkable scavenging capability. Therefore, these studies provide reference for further research and rational development of A. sinensis polysaccharide. PMID- 28987353 TI - Characterization of metabolite profiles from the leaves of green perilla (Perilla frutescens) by ultra high performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry and screening for their antioxidant properties. AB - The objective of this research was to access the determination of metabolite profiles and antioxidant properties in the leaves of green perilla (Perilla frutescens), where these are considered functional and nutraceutical substances in Korea. A total of 25 compositions were confirmed as six phenolic acids, two triterpenoids, eight flavonoids, seven fatty acids, and two glucosides using an ultra high performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-Q-TOF-MS/MS) technique from the methanol extract of this species. The individual and total compositions exhibited significant differences, especially rosmarinic acid (10), and linolenic acids (22 and 23) were detected as the predominant metabolites. Interestingly, rosmarinic acid (10) was observed to have considerable differences with various concentrations in three samples (Doryong, 6.38 MUg/g; Sinseong, 317.60 MUg/g; Bongmyeong, 903.53 MUg/g) by UPLC analysis at 330 nm. The scavenging properties against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3 ethylbenzthiazoline-6-sulphonic acid) (ABTS) radicals also showed potent effects with remarkable differences at a concentration of 100 MUg/mL, and their abilities were as follows: Sinseong (DPPH, 86%; ABTS, 90%) > Bongmyeong (71% and 84%, respectively) > Doryong (63% and 73%, respectively). Our results suggest that the antioxidant activities of green perilla leaves are correlated with metabolite contents, especially the five major compositions 10 and 22-25. Moreover, this study may be useful in evaluating the relationship between metabolite composition and antioxidant activity. PMID- 28987354 TI - Determination of underivatized amino acids to evaluate quality of beer by capillary electrophoresis with online sweeping technique. AB - Capillary electrophoresis (CE) with ultraviolet detection was applied to determine underivatized amino acids in beer, based on the coordination interaction of copper ions and amino acids. An online sweeping technique was combined with CE to improve detection sensitivity. Using the United Nations Food Agriculture Organization/World Health Organization model of essential amino acid pattern and flavor of amino acids, the quality and taste in three kinds of beer were evaluated. It was found that Beer2 had higher quality than the other two kinds and the content of phenylalanine, proline, serine, and isoleucine was relatively large in all three kinds of beers with a great influence on beer flavor. Optimal conditions for separation were as follows: 50mM CuSO4 at pH 4.40 as buffer; total length of fused silica capillary, 73 cm; effective length, 65 cm; separation voltage, 22.5 kV; and optimized sweeping condition, 70 seconds. In the appropriate range, linearity (r2 > 0.9989), precision with a relative standard deviation < 8.05% (n = 5), limits of detection (0.13-0.25 MUg/mL), limit of quantification (0.43-0.83 MUg/mL), and recovery (80.5-115.8%) were measured. This method was shown to be applicable to the separation of amino acids in beer and to perform quantitative analysis directly without derivatization for the first time. PMID- 28987355 TI - Rapid determination of capsaicinoids by colorimetric method. AB - Capsaicinoids, the pungent component of chili peppers, are generally analyzed by precise analytical techniques, such as gas chromatography and high-performance liquid chromatography (HPLC), but these are not practical for the mass analyses of samples. To analyze mass samples rapidly, a colorimetric method was suggested. In this work, pigments and capsaicinoids were efficiently separated from chili pepper extract by sequential solid-liquid extraction and liquid-liquid extraction in test tubes followed by a colorimetric analysis on the capsaicinoids by a selective chromogenic reaction with Gibbs reagent (2,6-dichloroquinone-4 chloroimide). In the comparison of the capsaicinoid content by the colorimetric method and HPLC using acetone extracts of fresh pepper and dry red pepper as samples, R2 was 0.9973 and 0.9816, respectively, which shows a high linear correlation. In addition, a minimum of 1 MUg/mL capsaicinoids can be detected and it was therefore determined that the method can efficiently analyze a great quantity of samples in a short time. PMID- 28987356 TI - Enhanced active extracellular polysaccharide production from Ganoderma formosanum using computational modeling. AB - Extracellular polysaccharide (EPS) is one of the major bioactive ingredients contributing to the health benefits of Ganoderma spp. In this study, response surface methodology was applied to determine the optimal culture conditions for EPS production of Ganoderma formosanum. The optimum medium composition was found to be at initial pH 5.3, 49.2 g/L of glucose, and 4.9 g/L of yeast extract by implementing a three-factor-three-level Box-Behnken design. Under this condition, the predicted yield of EPS was up to 830.2 mg/L, which was 1.4-fold higher than the one from basic medium (604.5 mg/L). Furthermore, validating the experimental value of EPS production depicted a high correlation (100.4%) with the computational prediction response model. In addition, the percentage of beta glucan, a well-recognized bioactive polysaccharide, in EPS was 53+/-5.5%, which was higher than that from Ganoderma lucidum in a previous study. Moreover, results of monosaccharide composition analysis indicated that glucose was the major component of G. formosanum EPS, supporting a high beta-glucan percentage in EPS. Taken together, this is the first study to investigate the influence of medium composition for G. formosanum EPS production as well as its beta-glucan composition. PMID- 28987357 TI - The effect of vacuum packaging on histamine changes of milkfish sticks at various storage temperatures. AB - The effects of polyethylene packaging (PEP) (in air) and vacuum packaging (VP) on the histamine related quality of milkfish sticks stored at different temperatures (-20 degrees C, 4 degrees C, 15 degrees C, and 25 degrees C) were studied. The results showed that the aerobic plate count (APC), pH, total volatile basic nitrogen (TVBN), and histamine contents increased as storage time increased when the PEP and VP samples were stored at 25 degrees C. At below 15 degrees C, the APC, TVBN, pH, and histamine levels in PEP and VP samples were retarded, but the VP samples had considerably lower levels of APC, TVBN, and histamine than PEP samples. Once the frozen fish samples stored at -20 degrees C for 2 months were thawed and stored at 25 degrees C, VP retarded the increase of histamine in milkfish sticks as compared to PEP. In summary, this result suggested the milkfish sticks packed with VP and stored below 4 degrees C could prevent deterioration of product quality and extend shelf-life. PMID- 28987358 TI - Regulatory efficacy of fermented plant extract on the intestinal microflora and lipid profile in mildly hypercholesterolemic individuals. AB - In recent years, the use of fermented plant products to protect against various metabolic syndromes has been increasing enormously. The objective of this study was to check the regulatory efficacy of fermented plant extract (FPE) on intestinal microflora, lipid profile, and antioxidant status in mildly hypercholesterolemic volunteers. Forty-four mildly hypercholesterolemic individuals (cholesterol 180-220 mg/dL) were recruited and assigned to two groups: experimental or placebo. Volunteers were requested to drink either 60 mL of FPE or placebo for 8 weeks. Anthropometric measurements were done in the initial, 4th, 8th, and 10th weeks. The anthropometric parameters such as body weight, body fat, and body mass index were markedly lowered (p<0.05) on FPE intervention participants. Moreover, the total antioxidant capacity and total phenolics in plasma were considerably increased along with a reduction (p<0.05) in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c) after FPE supplementation. Participants who drank FPE showed a pronounced increase (p<0.05) in the number of beneficial bacteria such as Bifidobacterium spp. and Lactobacillus spp., whereas the number of harmful bacteria such as Escherichia coli and Clostridium perfringens (p<0.05) were concomitantly reduced. Furthermore, the lag time of LDL oxidation was substantially ameliorated in FPE administered group, thus indicating its antioxidative and cardioprotective properties. Treatment with FPE substantially improved the intestinal microflora and thereby positively regulated various physiological functions by lowering the anthropometric parameters, TC, and LDL-c, and remarkably elevated the antioxidant capacity and lag time of LDL oxidation. Therefore, we recommended FPE beverage for combating hypercholesterolemia. PMID- 28987359 TI - In vitro assay to estimate tea astringency via observing flotation of artificial oil bodies sheltered by caleosin fused with histatin 3. AB - Astringency, a sensory characteristic of food and beverages rich in polyphenols, mainly results from the formation of complexes between polyphenols and salivary proteins, causing a reduction of the lubricating properties of saliva. To develop an in vitro assay to estimate the astringency of oolong tea infusion, artificial oil bodies were constituted with sesame oil sheltered by a modified caleosin fused with histatin 3, one of the human salivary small peptides. Aggregation of artificial oil bodies was induced when they were mixed with oolong tea infusion or its major polyphenolic compound, (-)-epigallocatechin gallate (EGCG) of 100MUM as observed in light microscopy. The aggregated artificial oil bodies gradually floated on top of the solution and formed a visible milky layer whose thickness was in proportion to the concentrations of tea infusion. This assay system was applied to test four different oolong tea infusions with sensory astringency corresponding to their EGCG contents. The result showed that relative astringency of the four tea infusions was correlated to the thickness of floated artificial oil bodies, and could be estimated according to the standard curve generated by simultaneously observing a serial dilution of the tea infusion with the highest astringency. PMID- 28987360 TI - Physicochemical properties and anticoagulant activity of polyphenols derived from Lachnum singerianum. AB - In this study, polyphenols (LSP) were obtained from the fermentation broth of Lachnum singerianum. Two fractions were isolated by Sephadex LH-20 chromatographic column, and the primary fraction (LSP-1) was collected. The comprehensive physicochemical properties of phenolic acids and polyhydroxy phenolic compounds of LSP-1 were determined by UV-visible spectroscopy, Fourier transform infrared spectroscopy, and gas chromatography-mass spectrometry. Results of anticoagulant activity assay in vitro showed that LSP-1 could lengthen prothrombin time, activated partial thromboplastin time, and thrombin time of mouse plasma. In addition, anticoagulant activity results in vivo showed that high dose of LSP-1 could significantly prolong bleeding time, coagulation time, prothrombin time, activated partial thromboplastin time, and thrombin time of hypercoagulable mice induced by adrenaline, reduce the content of fibrinogen and enhance antithrombin III activity. All results indicated that the LSP-1 could serve well as an anticoagulant, and might be used as a potential natural drug candidate for thrombosis. PMID- 28987361 TI - Comparative effect of horse gram and black gram on inflammatory mediators and antioxidant status. AB - A balanced diet is important for the overall wellbeing of an individual. Pulses are an important part of a nutritive diet. Pulses have been consumed for at least 10,000 years and are among the most extensively used foods in the world. They are a rich source of protein and fiber, as well as a significant source of vitamins and minerals, such as iron, zinc, and magnesium. The purpose of this study was to compare the effect of two pulses, horse gram and black gram, on inflammatory mediators and the antioxidant enzymes. Two sets of experiments were conducted in rats which were fed with boiled and unboiled horse gram and black gram, at a dose of 100 mg/100 g body weight, for 21 days and 60 days. The results showed that horse gram supplementation for 21 days and 60 days significantly increased the activities of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase and showed no significant changes in the activities of the inflammatory mediators such as cyclooxygenase, lipoxygenase, myeloperoxidase, nitric oxide synthase, monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-alpha), interleukin-1-beta (IL-1beta), etc. However, the black gram (with skin and without skin) supplementation significantly increased activities of the inflammatory mediators and showed a significant decrease in the antioxidant enzymes in both the 21-day and 60-day experiments. Thus, these preliminary results demonstrate the anti-inflammatory and antioxidant potential of horse gram and the proinflammatory effects of black gram in rats. This is in accordance with the dietary regime advised by Ayurveda practitioners, where horse gram is to be included and black gram is to be excluded from the diet for conditions such as rheumatoid arthritis. Further studies are to be conducted to validate the same. PMID- 28987362 TI - The stimulating effects of polyphenol and protein fractions from jelly fig (Ficus awkeotsang Makino) achenes against proliferation of leukemia cells. AB - This study aimed to investigate the direct and immune-stimulated antiproliferative activities of jelly fig achenes fractions including pectinesterase inhibitors, crude polyphenols extract, and purified polyphenols extract (PP). Beside the measurement of cell viability of U937, the quantity of cytokines in conditioned medium and morphologic changes in leukemia were observed. After surveying all fractions in jelly fig, the obtained fractions of polyphenol exhibited the highest stimulating effects and directly cytotoxic effects against leukemia with the lowest effect found in protein fractions. The leukemia treated by our PP fraction showed dose-dependent response between the concentration and G2/M cell numbers of the U937 cells. The PP fraction had more pronounced effect on immune-stimulated than direct antiproliferative activities. The finding was also supported by morphological analysis by showing the formation of apoptotic bodies and differentiation from immature U937 cells into mature monocytes/macrophages on cells cultured with PP-conditioned medium. In conclusion, polyphenol fraction of pectinesterase inhibitors from jelly fig showed the immune-stimulated antiproliferative activities against U937 cell. PMID- 28987363 TI - Extract from Mulberry (Morus australis) leaf decelerate acetaminophen induced hepatic inflammation involving downregulation of myeloid differentiation factor 88 (MyD88) signals. AB - Acetaminophen (APAP) induced inflammation and oxidative stress can cause cell death to induce liver damage. The antioxidative and anti-inflammatory effect of Mulberry (Morus australis) leaf extract (MLE) was shown in previous studies. In this study, we investigated the modulation of MLE on APAP induced inflammation and oxidative stress in rat liver injury or liver cancer cell (HepG2). Wistar rat was fed orally with MLE (0.5% or 1.0 %) for 1 week, and then, 900 mg/kg of APAP was injected intraperitoneally (i.p.). Pretreatment of MLE decreased obvious foci of inflammatory cell infiltration in liver. It also reduced the expression of inflammatory parameters including cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and nuclear factor kappa B (NF-kappaB) in liver. Treating with MLE increased the antioxidative enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase. Giving APAP to HepG2 hepatocyte was conducted to elucidate the mechanism of MLE or its functional components. The result showed that APAP upregulated hepatic protein expression of (myeloid differentiation factor 88) MyD88, nuclear factor kappa B (NF-kB), inhibitor of kappa B (IkB), c-Jun N-terminal kinases (JNK), and receptor interacting proteins (RIP1 and RIP3). Pretreatment of MLE, gallic acid (GA), gallocatechin gallate (GCG), or protocatechuic acid (PCA) suppressed the indicated protein expression. These findings confirmed that MLE has the potential to protect liver from APAP induced inflammation, and the protecting mechanism might involve decreasing oxidative stress and regulating the innate immunity involving MyD88. PMID- 28987364 TI - Taiwanese and Japanese yam (Dioscorea spp.) extracts attenuate doxorubicin induced cardiotoxicity in mice. AB - The present study was designed to explore whether yam could protect the heart from doxorubicin (DOX)-induced oxidative stress leading to cardiotoxicity in vivo. In this study, the protective effects of water and ethanol extracts of three varieties of yam, including water extracts of Dioscorea japonica Thunb., ethanol extracts of D. japonica Thunb., water extracts of Dioscorea alata, ethanol extracts of D. alata, water extracts of Dioscorea purpurea, and ethanol extracts of D. purpurea, against DOX-induced cardiotoxicity in experimental mice were evaluated. DOX treatment led to significant decreases in the ratio of heart weight to body weight and heart rate, and increases in blood pressure and the serum level of lactate dehydrogenase, a marker of cardiotoxicity, were recovered by yam extracts, especially in water extracts of D. alata. Yam extracts also decreased the cardiac levels of thiobarbituric acid relative substances, reactive oxygen species, and inflammatory factors, as well as the expression of nuclear factor kappa B, while ethanol extracts of D. japonica Thunb. and D. purpurea were shown to be more potent. Moreover, yam extracts had a role in increasing the activities of glutathione peroxidase and superoxide dismutase, thus improving the DOX-induced alterations in oxidative status in the heart tissue of DOX-treated mice. All ethanol extracts of yam exhibited their antiapoptotic abilities on caspase-3 activation and mitochondrial dysfunction, and ethanol extracts of D. alata still exerted a superior effect. Based on these findings, it can be concluded that yam has significant cardioprotective properties against DOX induced damage via its multiple effects on antioxidant, anti-inflammatory, or antiapoptotic activities. PMID- 28987365 TI - Anti-oxidant activity and major chemical component analyses of twenty-six commercially available essential oils. AB - This study analyzed 26 commercially available essential oils and their major chemical components to determine their antioxidant activity levels by measuring their total phenolic content (TPC), reducing power (RP), beta-carotene bleaching (BCB) activity, trolox equivalent antioxidant capacity (TEAC), and 1,1-diphenyl-2 picrylhydrazyl free radical scavenging (DFRS) ability. The clove bud and thyme borneol essential oils had the highest RP, BCB activity levels, and TPC values among the 26 commercial essential oils. Furthermore, of the 26 essential oils, the clove bud and ylang ylang complete essential oils had the highest TEAC values, and the clove bud and jasmine absolute essential oils had the highest DFRS ability. At a concentration of 2.5 mg/mL, the clove bud and thyme borneol essential oils had RP and BCB activity levels of 94.56% +/- 0.06% and 24.64% +/- 0.03% and 94.58% +/- 0.01% and 89.33% +/- 0.09%, respectively. At a concentration of 1 mg/mL, the clove bud and thyme borneol essential oils showed TPC values of 220.00 +/- 0.01 and 69.05 +/- 0.01 mg/g relative to gallic acid equivalents, respectively, and the clove bud and ylang ylang complete essential oils had TEAC values of 809.00 +/- 0.01 and 432.33 +/- 0.01 MUM, respectively. The clove bud and jasmine absolute essential oils showed DFRS abilities of 94.13% +/- 0.01% and 78.62% +/- 0.01%, respectively. Phenolic compounds of the clove bud, thyme borneol and jasmine absolute essential oils were eugenol (76.08%), thymol (14.36%) and carvacrol (12.33%), and eugenol (0.87%), respectively. The phenolic compounds in essential oils were positively correlated with the RP, BCB activity, TPC, TEAC, and DFRS ability. PMID- 28987366 TI - The impact of gallic acid on the methotrexate-induced kidney damage in rats. AB - Prolonged use of an antineoplastic agent methotrexate (MTX), can cause numerous side effects such as nephrotoxicity. The aim of this study was to examine the effects of MTX on kidneys and demonstrate the protective effects of gallic acid (GA). Twenty-four, male, rats distributed into three groups. Each groups consisted eight rats and only saline was administered to the control group. The MTX group received a single dose (20 mg/kg) MTX intraperitoneally. The MTX + GA group received same dose MTX and 100 mg/kg GA orally during the 7 days. Renal functions, oxidative stress markers, histopathological and immunohistochemical changes were evaluated at the end of the experiment. Blood urea nitrogen, creatinine, uric acid levels and tissue oxidative stress markers, total oxidant status and oxidative stress index levels significantly increased and total antioxidant status levels significantly decreased in MTX group compared with the control group. At the histopathological examination hemorrhages, tubular cell necrosis, glomerulosclerosis, inflammatory cell infiltrations and proteinous materials in tubules were noticed in MTX group. Immunohistochemical examination revealed that increased expressions of serum amyloid A (SAA), tumor necrosis factor alpha (TNF-alpha), prostaglandin E2 (PGE-2) and C-reactive protein (CRP) in tubular epithelial cells of kidneys in this group. There were no immunoreaction with SAA and CRP, only small number of PGE-2 and TNF-alpha positive tubular epithelial cells were observed in MTX + GA group. In conclusion, all evidence suggested that oxidative stress caused MTX-induced nephrotoxicity and GA prevent the kidney from the nephrotoxicity due to its antioxidant and anti inflammatory activities. PMID- 28987367 TI - Antihemolytic and antioxidant properties of pearl powder against 2,2'-azobis(2 amidinopropane) dihydrochloride-induced hemolysis and oxidative damage to erythrocyte membrane lipids and proteins. AB - Pearl powder, a well-known traditional mineral medicine, is reported to be used for well-being and to treat several diseases from centuries in Taiwan and China. We investigated the in vitro antihemolytic and antioxidant properties of pearl powder that could protect erythrocytes against 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced oxidative damage to membrane proteins/lipids. Human erythrocytes were incubated with different concentrations of pearl powder (50-200 MUg/mL) for 30 minutes and then exposed to AAPH for 2-6 hours. We found that AAPH alone time dependently increased the oxidative hemolysis of erythrocytes, while pearl powder pretreatment substantially inhibited the hemolysis in a concentration-/time-dependent manner. AAPH-induced oxidative damage to erythrocyte membrane lipids was evidenced by the elevated malondialdehyde (MDA) levels. However, pearl powder remarkably inhibited the malondialdehyde formation, and the 200 MUg/mL concentration showed almost similar malondialdehyde values to the control. Furthermore, pearl powder suppressed the AAPH-induced high-molecular-weight protein formation and concomitantly increased the low-molecular-weight proteins in erythrocytes. Antioxidant potential that was measured as superoxide dismutase activity and glutathione content was significantly dropped by AAPH incubation, which suggests the vulnerability of erythrocytes to AAPH-induced oxidative stress. Noteworthy, erythrocytes pretreated with pearl powder showed restored superoxide dismutase activity and glutathione levels against AAPH-induced loss. Our findings conclude that pearl powder attenuate free radical-induced hemolysis and oxidative damage to erythrocyte membrane lipids/proteins. The potent antioxidant property of pearl powder may offer protection from free radical-related diseases. PMID- 28987368 TI - Dunaliella salina alga extract inhibits the production of interleukin-6, nitric oxide, and reactive oxygen species by regulating nuclear factor-kappaB/Janus kinase/signal transducer and activator of transcription in virus-infected RAW264.7 cells. AB - Recent investigations have demonstrated that carotenoid extract of Dunaliella salina alga (Alga) contains abundant beta-carotene and has good anti-inflammatory activities. Murine macrophage (RAW264.7 cells) was used to establish as an in vitro model of pseudorabies virus-induced reactive oxygen species (ROS) response. In this study, antioxidant activities of Alga were measured based on 2,2-diphenyl 1-picrylhydrazyl (DPPH) radical scavenging, trolox equivalent antioxidant capacity assays, reducing power, and virus-induced ROS formation in RAW264.7 cells. Anti-inflammatory activities of Alga were assessed by its ability to inhibit the production of interleukin-6 and nitric oxide (NO) using enzyme-linked immunosorbent assay, then the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway was investigated by measuring the inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor-kappaB (p50 and p65), JAK, STAT-1/3, and suppressor of cytokine signaling 3 (SOCS3) by Western blotting. In addition, Alga inhibited virus replication by plaque assay. Our results showed that the Alga had high antioxidant activity, significantly reduced the virus-induced accumulation of ROS, and inhibited the levels of nitric oxide and interleukin-6. Further studies revealed that Alga also downregulated the gene and protein expressions of iNOS, COX-2, nuclear factor-kappaB (p50 and p65), and the JAK/STAT pathway. The inhibitory effects of Alga were similar to pretreatment with specific inhibitors of JAK and STAT-3 in pseudorabies virus infected RAW264.7 cells. Alga enhanced the expression of SOCS3 to suppress the activity of the JAK/STAT signaling pathway in pseudorabies virus-infected RAW264.7 cells. In addition, Alga has decreased viral replication (p < 0.005) at an early stage. Therefore, our results demonstrate that Alga inhibits ROS, interleukin6, and nitric oxide production via suppression of the JAK/STAT pathways and enhanced the expression of SOCS3 in virus-infected RAW264.7 cells. PMID- 28987369 TI - The regulatory effects of fish oil and chitosan on hepatic lipogenic signals in high-fat diet-induced obese rats. AB - The present study investigated the regulatory effects of fish oil and chitosan on the signals of hepatic lipid metabolism and the postulated mechanism in high-fat diet-induced obese rats. Diet supplementation of chitosan and fish oil efficiently suppressed the increased weights in body and livers of high-fat diet fed rats. Supplementation of chitosan and fish oil significantly decreased the activities of hepatic lipid biosynthesis-related enzymes and efficiently regulated plasma lipoprotein homeostasis. Both chitosan and fish oil significantly ameliorated the alterations in the protein expressions of hepatic lipogenic transcription factors (LXRalpha and PPARalpha), and could also significantly regulate the downstream hepatic lipogenic genes (FAS, HMGCR, CYP7A1, FATP, FABP, AOX, and ABCA) expressions in high-fat diet-fed rats. These results suggest that both fish oil and chitosan exerts downregulative effects on hepatic lipid metabolism in high-fat diet-induced obese rats via the LXRalpha inhibition and PPARalpha activation, which further affect the expressions of hepatic lipogenesis-associated genes. PMID- 28987370 TI - Red algae (Gelidium amansii) hot-water extract ameliorates lipid metabolism in hamsters fed a high-fat diet. AB - The purpose of this study was to investigate the effects of Gelidium amansii (GA) hot-water extracts (GHE) on lipid metabolism in hamsters. Six-week-old male Syrian hamsters were used as the experimental animals. Hamsters were divided into four groups: (1) control diet group (CON); (2) high-fat diet group (HF); (3) HF with GHE diet group (HF + GHE); (4) HF with probucol diet group (HF + PO). All groups were fed the experimental diets and drinking water ad libitum for 6 weeks. The results showed that GHE significantly decreased body weight, liver weight, and adipose tissue (perirenal and paraepididymal) weight. The HF diet induced an increase in plasma triacylglycerol (TG), total cholesterol (TC), low-density lipoprotein cholesterol and very-low-density lipoprotein cholesterol levels. However, GHE supplementation reversed the increase of plasma lipids caused by the HF diet. In addition, GHE increased fecal cholesterol, TG and bile acid excretion. Lower hepatic TC and TG levels were found with GHE treatment. GHE reduced hepatic sterol regulatory element-binding proteins (SREBP) including SREBP 1 and SREBP 2 protein expressions. The phosphorylation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) protein expression in hamsters was decreased by the HF diet; however, GHE supplementation increased the phosphorylation of AMPK protein expression. Our results suggest that GHE may ameliorate lipid metabolism in hamsters fed a HF diet. PMID- 28987371 TI - Morphological and chemical analyses of Eriocauli Flos sold in Taiwan markets. AB - Eriocauli Flos (Gujingcao; EF), the dried capitulum with the peduncle of Eriocaulon buergerianum Koern. (Eriocaulaceae), is a Chinese herbal medicine for treating eye diseases and inflammation. However, several species of the Eriocaulon genus are used as substitutes in different areas. To examine the species of EF used in Taiwan and to establish the quality control platform, morphological and chemical analyses have been performed. Ten major compounds, including apigenin (7) and its 7-O-beta-D-glucopyranoside (1) and 7-O-(6-O-E coumaroyl)-beta-D-glucopyranoside (6), hispidulin (8) and its 7-O-beta-D glucopyranoside (2) and 7-O-(6-O-E-coumaroyl)-beta-D-glucopyranoside (5), jaceosidin (9) and its 7-O-beta-D-glucopyranoside (3), and toralactone (10) and its 9-O-beta-D-glucopyranosyl(1->6)-beta-D-glucopyranoside (4), were isolated and identified from commercially available EF. Morphological investigation showed that two kinds of EFs and most of the EFs sold in Taiwan herbal markets are capitulum without the peduncle. A simultaneous high performance liquid chromatography and ultra performance liquid chromatography analyses of multiple components (1-10) in commercially available EFs, collected from different areas of Taiwan, was conducted. Results showed wide variations in morphology and chemical profiles between capitulum with and without the peduncle. In comparison with an authentic E. buergerianum, we found not only the morphology but also the chemical profile was different from both collected samples. In terms of the morphological examination, the samples without peduncle are closer to the authentic one. To ensure the correct EF materia medica is used in Taiwan so as to guarantee their therapeutic efficacy in clinical practice, further monitoring is necessary. PMID- 28987372 TI - Qualitative and quantitative characterization of secondary metabolites and carbohydrates in Bai-Hu-Tang using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and ultraperformance liquid chromatography coupled with photodiode array detector. AB - Bai-Hu-Tang (BHT), a classic traditional Chinese medicine (TCM) formula used for clearing heat and promoting body fluid, consists of four traditional Chinese medicines, i.e., Gypsum Fibrosum (Shigao), Anemarrhenae Rhizoma (Zhimu), Glycyrrhizae Radix et Rhizoma Praeparata cum Melle (Zhigancao), and nonglutinous rice (Jingmi). The chemical composition of BHT still remains largely elusive thus far. To qualitatively and quantitatively characterize secondary metabolites and carbohydrates in BHT, here a combination of analytical approaches using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and ultraperformance liquid chromatography coupled with photodiode array detector was developed and validated. A total of 42 secondary metabolites in BHT were tentatively or definitely identified, of which 10 major chemicals were quantified by the extracting ion mode of quadrupole time-of-flight mass spectrometry. Meanwhile, polysaccharides, oligosaccharides, and monosaccharides in BHT were also characterized via sample pretreatment followed by sugar composition analysis. The quantitative results indicated that the determined chemicals accounted for 35.76% of the total extract of BHT, which demonstrated that the study could be instrumental in chemical dissection and quality control of BHT. The research deliverables not only laid the root for further chemical and biological evaluation of BHT, but also provided a comprehensive analytical strategy for chemical characterization of secondary metabolites and carbohydrates in traditional Chinese medicine formulas. PMID- 28987373 TI - Quality assessment of trace Cd and Pb contaminants in Thai herbal medicines using ultrasound-assisted digestion prior to flame atomic absorption spectrometry. AB - A simple, efficient, and reliable ultrasound-assisted digestion (UAD) procedure was used for sample preparation prior to quantitative determination of trace Cd and Pb contaminants in herbal medicines using flame atomic absorption spectrometry. The parameters influencing UAD such as the solvent system, sample mass, presonication time, sonication time, and digestion temperature were evaluated. The efficiency of the proposed UAD procedure was evaluated by comparing with conventional acid digestion (CAD) procedure. Under the optimum conditions, linear calibration graphs in a range of 2-250 MUg/L for Cd, and 50 1000 MUg/L for Pb were obtained with detection limits of 0.56 MUg/L and 10.7 MUg/L for Cd and Pb, respectively. The limit of quantification for Cd and Pb were 1.87 MUg/L and 40.3 MUg/L, respectively. The repeatability for analysis of 10 MUg/L for Cd and 100 MUg/L for Pb was 2.3% and 2.6%, respectively. The accuracy of the proposed method was evaluated by rice flour certified reference materials. The proposed method was successfully applied for analysis of trace Cd and Pb in samples of various types of medicinal plant and traditional medicine consumed in Thailand. Most herbal medicine samples were not contaminated with Cd or Pb. The contaminant levels for both metals were still lower than the maximum permissible levels of elements in medicinal plant materials and finished herbal products sets by the Ministry of Public Health of Thailand. The exception was the high level of Cd contamination found in two samples of processed medicinal plants. PMID- 28987374 TI - Exploration of ethyl anthranilate-loaded monolithic matrix-type prophylactic polymeric patch. AB - Compromised stability of pharmaceutical formulations loaded with volatiles is a serious problem associated with devices designed to deliver volatile compounds. The present study has been focused to evaluate the stability potential of matrix type polymeric patches composed of volatile ethyl anthranilate for prophylaxis against vector-borne diseases. Ethyl anthranilate-loaded matrix-type polymeric patches were fabricated by solvent evaporation method on an impermeable backing membrane and attached to temporary release liners. Stability testing of the polymeric patches was performed as per the International Conference on Harmonization (ICH) guidelines for 6 months under accelerated conditions. In addition, the quantification of residual solvents was also performed as per the ICH guidelines. After conducting the stability studies for 6 months, the optimized patches showed the best possible results with respect to uniformity of drug content, physical appearance, and other analytical parameters. Furthermore, the amount of residual solvent was found well below the accepted limit. Thus, the present report outlined the analytical parameters to be evaluated to ensure the stability of a certain devices consisting of volatile compounds. PMID- 28987375 TI - Phosphorylation and antiaging activity of polysaccharide from Trichosanthes peel. AB - Polysaccharides from Trichosanthes peel (TPP) were obtained by ultrasound assisted extraction. TPP-1 was separated from the TPP by Sephadex G-100 column chromatography. Phosphorylation of TPP-1 was carried out and phosphorylated TPP-1 was named as PTTP-1. The results of infrared spectra, 13C nuclear magnetic resonance spectra and 31P nuclear magnetic resonance spectra showed that the main structure of PTPP-1 was similar to that of TPP-1 and -H2PO3 groups which were conjugated to C-6 of ->4)-alpha-D-Manp-(1->, C-4 of ->6)-alpha-D-Galp-(1->, C-2 and C-3 of ->1)-alpha-L-Araf, C-2 of ->1)-alpha-L-Araf-(3->, and C-6 and C-3 of >1)-alpha-D-Glcp. In vivo antiaging activity results proved that TTP-1 and PTTP-1 could both significantly improve the body weight, spleen index, and thymus index of the D-galactose-induced aging mice, increase the levels of superoxide dismutase, catalase, glutathione peroxidase, and reduce malondialdehyde contents in the liver, brain, and serum of aging mice. These results indicated that both TPP-1 and PTTP-1 presented significant antiaging activity. Moreover, PTTP-1 showed stronger antiaging effects in aging mice, indicating that phosphorylation improved antiaging effect. PMID- 28987376 TI - Pyrrolizidine alkaloid-derived DNA adducts are common toxicological biomarkers of pyrrolizidine alkaloid N-oxides. AB - There are 660 pyrrolizidine alkaloids (PAs) and PA N-oxides present in the plants, with approximately half being possible carcinogens. We previously reported that a set of four PA-derived DNA adducts is formed in the liver of rats administered a series of hepatocarcinogenic PAs and a PA N-oxide. Based on our findings, we hypothesized that this set of DNA adducts is a common biological biomarker of PA-induced liver tumor formation. In this study, we determined that rat liver microsomal metabolism of five hepatocarcinogenic PAs (lasiocarpine, retrorsine, riddelliine, monocrotaline, and heliotrine) and their corresponding PA N-oxides produced the same set of DNA adducts. Among these compounds, lasiocarpine N-oxide, retrorsine N-oxide, monocrotaline N-oxide, and heliotrine N oxide are for first time shown to be able to produce these DNA adducts. These results further support the role of these DNA adducts as potential common biomarkers of PA-induced liver tumor initiation. PMID- 28987377 TI - Analysis of bioactive constituents from the leaves of Amorpha fruticosa L. AB - : Amorpha fruticosa L. is a Chinese folk medicine and rich in polyphenols. Fifteen known compounds were isolated and identified from the leaves of A. fruticosa L. They are tephrosin (1), 6a,12a-dehydrodeguelin (2), vitexin (3), afrormosin-7-O-beta-d-glucopyranoside (4), 2"-O-alpha-l-rhamnopyranosyl isovitexin (5), rutin (6), chrysoeriol (7), 7-O-methylluteolin (8), trans-p coumaric acid (9), 2-benzyl-4,6-dihydroxybenzoic acid-4-O-beta-d-glucopyranoside (10), formononetin (11), quercetin (12), apigenin (13), beta-sitosterol (14), and beta-daucosterol (15). Compounds 3, 4, 5, and 7-9 were isolated from A. fruticosa L. for the first time. Cytotoxicity of individual compounds 3-10 and 90% ethanol extract against human cancer cell lines HCT116 and HepG2 were reported. The results suggested that compounds 7 and 8, and the crude extract exhibited inhibitory effects on human cancer cell line HCT116, at concentrations of 100 MUg/mL, 5 MUg/mL, and 25 MUg/mL at <60% of cell viability rate, respectively. In addition, a valid high-performance liquid chromatography diode array detector method was established to quantitatively analyze compounds 1-12 in the leaves of A. fruticosa L., which was harvested at three different stages of maturity from May 20 to August 10, 2014. The results demonstrated that contents were greatly influenced by the maturity. Total amounts of the analytical constituents gradually increased from May 20 to August 10, with the values ranging from 10.86 mg/g to 18.84 mg/g, whereas bioactive compounds 7 and 8 presented the opposite variation trend. The results of this study may provide data for further study and comprehensive utilization of A. fruticosa L. RESOURCE: PMID- 28987378 TI - Consistent discovery of frequent interval-based temporal patterns in chronic patients' data. AB - Increasingly, frequent temporal patterns discovered in longitudinal patient records are proposed as features for classification and prediction, and as means to cluster patient clinical trajectories. However, to justify that, we must demonstrate that most frequent temporal patterns are indeed consistently discoverable within the records of different patient subsets within similar patient populations. We have developed several measures for the consistency of the discovery of temporal patterns. We focus on time-interval relations patterns (TIRPs) that can be discovered within different subsets of the same patient population. We expect the discovered TIRPs (1) to be frequent in each subset, (2) preserve their "local" metrics - the absolute frequency of each pattern, measured by a Proportion Test, and (3) preserve their "global" characteristics - their overall distribution, measured by a Kolmogorov-Smirnov test. We also wanted to examine the effect on consistency, over a variety of settings, of varying the minimal frequency threshold for TIRP discovery, and of using a TIRP-filtering criterion that we previously introduced, the Semantic Adjacency Criterion (SAC). We applied our methodology to three medical domains (oncology, infectious hepatitis, and diabetes). We found that, within the minimal frequency ranges we had examined, 70-95% of the discovered TIRPs were consistently discoverable; 40 48% of them maintained their local frequency. TIRP global distribution similarity varied widely, from 0% to 65%. Increasing the threshold usually increased the percentage of TIRPs that were repeatedly discovered across different patient subsets within the same domain, and the probability of a similar TIRP distribution. Using the SAC principle, enhanced, for most minimal support levels, the percentage of repeating TIRPs, their local consistency and their global consistency. The effect of using the SAC was further strengthened as the minimal frequency threshold was raised. PMID- 28987379 TI - Evaluating the granularity balance of hierarchical relationships within large biomedical terminologies towards quality improvement. AB - Organizing the descendants of a concept under a particular semantic relationship may be rather arbitrarily carried out during the manual creation processes of large biomedical terminologies, resulting in imbalances in relationship granularity. This work aims to propose scalable models towards systematically evaluating the granularity balance of semantic relationships. We first utilize "parallel concepts set (PCS)" and two features (the length and the strength) of the paths between PCSs to design the general evaluation models, based on which we propose eight concrete evaluation models generated by two specific types of PCSs: single concept set and symmetric concepts set. We then apply those concrete models to the IS-A relationship in FMA and SNOMED CT's Body Structure subset, as well as to the Part-Of relationship in FMA. Moreover, without loss of generality, we conduct two additional rounds of applications on the Part-Of relationship after removing length redundancies and strength redundancies sequentially. At last, we perform automatic evaluation on the imbalances detected after the final round for identifying missing concepts, misaligned relations and inconsistencies. For the IS-A relationship, 34 missing concepts, 80 misalignments and 18 redundancies in FMA as well as 28 missing concepts, 114 misalignments and 1 redundancy in SNOMED CT were uncovered. In addition, 6,801 instances of imbalances for the Part-Of relationship in FMA were also identified, including 3,246 redundancies. After removing those redundancies from FMA, the total number of Part-Of imbalances was dramatically reduced to 327, including 51 missing concepts, 294 misaligned relations, and 36 inconsistencies. Manual curation performed by the FMA project leader confirmed the effectiveness of our method in identifying curation errors. In conclusion, the granularity balance of hierarchical semantic relationship is a valuable property to check for ontology quality assurance, and the scalable evaluation models proposed in this study are effective in fulfilling this task, especially in auditing relationships with sub hierarchies, such as the seldom evaluated Part-Of relationship. PMID- 28987380 TI - The disturbed redox-balance in pulmonary fibrosis is modulated by the plant flavonoid quercetin. AB - Idiopathic pulmonary fibrosis (IPF) is characterized by a disturbed pulmonary redox balance associated with inflammation. To restore this balance, antioxidants are often suggested as therapy for IPF but previous clinical trials with these compounds and their precursors have not been successful in the clinic. The exogenous antioxidant quercetin, which has a versatile antioxidant profile and is effective in restoring a disturbed redox balance, might be a better candidate. The aim of this study was to evaluate the protective effect of quercetin on oxidative and inflammatory markers in IPF. Here, we demonstrate that IPF patients have a significantly reduced endogenous antioxidant defense, shown by a reduced total antioxidant capacity and lowered glutathione and uric acid levels compared to healthy controls. This confirms that the redox balance is disturbed in IPF. Ex vivo incubation with quercetin in blood of both IPF patients and healthy controls reduces LPS-induced production of the pro-inflammatory cytokines IL-8 and TNFalpha. This anti-inflammatory effect was more pronounced in the blood of the patients. Our pro-fibrotic in vitro model, consisting of bleomycin-triggered BEAS 2B cells, shows that quercetin boosts the antioxidant response, by increasing Nrf2 activity, and decreases pro-inflammatory cytokine production in a concentration-dependent manner. Collectively, our findings implicate that IPF patients may benefit from the use of quercetin to restore the disturbed redox balance and reduce inflammation. PMID- 28987382 TI - Arginine methyltransferase inhibitor 1 inhibits gastric cancer by downregulating eIF4E and targeting PRMT5. AB - Arginine methylation is carried out by protein arginine methyltransferase (PRMTs) family. Arginine methyltransferase inhibitor 1 (AMI-1) is mainly used to inhibit type I PRMT activity in vitro. However, the effects of AMI-1 on type II PRMT5 activity and gastric cancer (GC) remain unclear. In this study, we provided the first evidence that AMI-1 significantly inhibited GC cell proliferation and migration while induced GC cell apoptosis, and reduced the expression of PRMT5, eukaryotic translation initiation factor 4E (eIF4E), symmetric dimethylation of histone 3 (H3R8me2s) and histone 4 (H4R3me2s). In addition, AMI-1 inhibited tumor growth, downregulated eIF4E, H4R3me2s and H3R8me2s expression in mice xenografts model of GC. Collectively, our results suggest that AMI-1 inhibits GC by downregulating eIF4E and targeting type II PRMT5. PMID- 28987381 TI - Altered gene expression profiles in the lungs of benzo[a]pyrene-exposed mice in the presence of lipopolysaccharide-induced pulmonary inflammation. AB - Patients with inflammatory lung diseases are often additionally exposed to polycyclic aromatic hydrocarbons like B[a]P and B[a]P-induced alterations in gene expression in these patients may contribute to the development of lung cancer. Mice were intra-nasally treated with lipopolysaccharide (LPS, 20MUg/mouse) to induce pulmonary inflammation and subsequently exposed to B[a]P (0.5mg/mouse) by intratracheal instillation. Gene expression changes were analyzed in mouse lungs by RNA microarrays. Analysis of genes that are known to be involved in the cellular response to B[a]P indicated that LPS significantly inhibited gene expression of various enzymes linked to B[a]P metabolism, which was confirmed by phenotypic analyses of enzyme activity. Ultimately, these changes resulted in higher levels of B[a]P-DNA adducts in the lungs of mice exposed to B[a]P with prior LPS treatment compared to the lungs of mice exposed to B[a]P alone. Using principle component analysis (PCA), we found that of all the genes that were significantly altered in their expression, those that were able to separate the different exposure conditions were predominantly related to immune-response. Moreover, an overall analysis of differentially expressed genes indicated that cell-cell adhesion and cell-cell communication was inhibited in lungs of mice that received both B[a]P and LPS. Our results indicate that pulmonary inflammation increased the genotoxicity of B[a]P via inhibition of both phase I and II metabolism. Therefore, inflammation could be a critical contributor to B[a]P-induced carcinogenesis in humans. PMID- 28987383 TI - HSP90 inhibitor (NVP-AUY922) enhances the anti-cancer effect of BCL-2 inhibitor (ABT-737) in small cell lung cancer expressing BCL-2. AB - Small cell lung cancer (SCLC) cannot be efficiently controlled using existing chemotherapy and radiotherapy approaches, indicating the need for new therapeutic strategies. Although ABT-737, a B-cell lymphoma-2 (BCL-2) inhibitor, exerts anticancer effects against BCL-2-expressing SCLC, monotherapy with ABT-737 is associated with limited clinical activity because of the development of resistance and toxicity. Here, we examined whether combination therapy with ABT 737 and heat shock protein 90 (HSP90) inhibitor NVP-AUY922 exerted synergistic anticancer effects on SCLC. We found that the combination of ABT-737 and NVP AUY922 synergistically induced the apoptosis of BCL-2-expressing SCLC cells. NVP AUY922 downregulated the expression of AKT and ERK, which activate MCL-1 to induce resistance against ABT-737. The synergistic effect was also partly due to blocking NF-kappaB activation, which induces anti-apoptosis protein expressions. However, interestingly, targeting BCL-2 and MCL-1 or BCL2 and NF-kappaB did not induce the cytotoxicity. In conclusion, our study showed that combination of BCL2 inhibitor with HSP90 inhibitor increased activity in in vitro and in vivo study in only BCL-2 expressing SCLC compared to either single BCL2 inhibitor or HSP inhibitor. The enhanced activity might be led by blocking several apoptotic pathways simultaneously rather than a specific pathway. PMID- 28987385 TI - SUMOylation of IQGAP1 promotes the development of colorectal cancer. AB - IQGAP1 is a conserved multifunctional protein implicated in tumorigenesis. An aberrant expression of IQGAP1 widely exists in many cancers, but the SUMOylation modification of IQGAP1 in carcinogenesis is unknown by now. Here we first time explore biological functions of IQGAP1 SUMOylation in promoting colorectal cancer progression in vitro and in vivo. The expression of IQGAP1 and its SUMOylation level are both increased in human colorectal carcinoma (CRC) cells and tissues. IQGAP1 is mainly SUMOylated by SUMO1 at the K1445 residue, which could stabilize IQGAP1 by reducing protein ubiquitination. IQGAP1 SUMOylation improves CRC cell growth, cell migration and tumorigenesis in vivo through activating the phosphorylation of ERK, MEK and AKT. While the SUMOylation site mutation at K1445 of IQGAP1 greatly reduces CRC cell proliferation, migration ability and tumor growth of CRC-xenograft mice by suppressing phosphorylation of ERK, MEK and AKT. Our findings discover the IQGAP1 SUMOylation is a novel regulatory mechanism to enhance tumorigenesis and development of CRC in vitro and in vivo. PMID- 28987386 TI - Autophagy in the "inflammation-carcinogenesis" pathway of liver and HCC immunotherapy. AB - Autophagy plays a dual role in many types of cancer, such as hepatocellular carcinoma (HCC). Autophagy seems to be inhibited and functions as a tumor suppression mechanism in the "inflammation-carcinogenesis" pathway of the liver, including hepatitis B virus and hepatitis C virus, alcoholic steatohepatitis and non-alcoholic steatohepatitis related HCC. However, in established tumors, autophagy plays a tumor-promoting role. Because of the varied function of autophagy in HCC, we hypothesized p62 as a marker to evaluate the autophagic level. Moreover, autophagy is critical in antigen presentation and homeostasis of immune cells and tumor microenvironment. Understanding the intricate relationships of autophagy, inflammation, and immunity provides us with new insights into HCC immunotherapy. PMID- 28987384 TI - Favorable biodistribution, specific targeting and conditional endosomal escape of RNA nanoparticles in cancer therapy. AB - The past decades have witnessed the successful transition of several nanotechnology platforms into the clinical trials. However, specific delivery of therapeutics to tumors is hindered by several barriers including cancer recognition and tissue penetration, particle heterogeneity and aggregation, and unfavorable pharmacokinetic profiles such as fast clearance and organ accumulation. With the advent of RNA nanotechnology, a series of RNA nanoparticles have been successfully constructed to overcome many of the aforementioned challenges for in vivo cancer targeting with favorable biodistribution profiles. Compared to other nanodelivery platforms, the physiochemical properties of RNA nanoparticles can be tuned with relative ease for investigating the in vivo behavior of nanoparticles upon systemic injection. The size, shape, and surface chemistry, especially hydrophobic modifications, exert significant impacts on the in vivo fate of RNA nanoparticles. Rationally designed RNA nanoparticles with defined stoichiometry and high homogeneity have been demonstrated to specifically target tumor cells while avoiding accumulation in healthy vital organs after systemic injection. RNA nanoparticles were proven to deliver therapeutics such as siRNA and anti-miRNA to block tumor growth in several animal models. Although the release of anti-miRNA from the RNA nanoparticles has achieved high efficiency of tumor regression in multiple animal models, the efficiency of endosomal escape for siRNA delivery needs further improvement. This review focuses on the advances and perspectives of this promising RNA nanotechnology platform for cancer targeting and therapy. PMID- 28987387 TI - MiR-17-5p enhances pancreatic cancer proliferation by altering cell cycle profiles via disruption of RBL2/E2F4-repressing complexes. AB - The members of the miR-17-92 cluster are upregulated in various cancers and function as a cluster of oncogenic miRNA. Our study characterized a new function of miR-17-5p, a member of the miR-17-92 cluster, in regulating cell proliferation in pancreatic cancer. Our results indicate that miR-17-5p was up-regulated in pancreatic adenocarcinoma and directly targeted the retinoblastoma-like protein 2 (RBL2), a tumor suppressor belonging to the Rb family. High levels of miR-17-5p and low levels of RBL2 were associated with poor prognosis. RBL2 interacted with the transcription factor E2F4 and bound to the promoter regions of the E2F target genes. Disruption of the RBL2/E2F4 complex by miR-17-5p overexpression shifted the activity of E2F from gene repressing to gene activating, which induced cell cycle entry and proliferation. These results suggest that miR-17-5p promoted proliferation in pancreatic ductal adenocarcinoma cells (PDAC), and altered cell cycle profiles in vivo and in vitro, by disrupting the RBL2/E2F4-associated gene repressing complexes via direct targeting of RBL2. The new regulatory network, involving miR-17-5p and RBL2, emerges as a new target of PDAC treatment. PMID- 28987388 TI - BMP4 promotes oxaliplatin resistance by an induction of epithelial-mesenchymal transition via MEK1/ERK/ELK1 signaling in hepatocellular carcinoma. AB - BACKGROUND: Bone morphogenetic protein-4 (BMP4) is a key regulator of epithelial mesenchymal transition (EMT), which is crucial for cancer cells to acquire chemoresistance. The effects of BMP4 on OXA sensitivity in HCC need to be elucidated. METHODS: Functional analysis of BMP4 on EMT-regulated OXA sensitivity was performed in human HCC specimens, in the HCC cell lines HepG2 and HCCLM3, and in a subcutaneous tumor model receiving OXA treatment. The downstream signaling targets of BMP4 in HCC were profiled and confirmed. RESULTS: BMP4 expression was significantly increased in HCC tissue, and was correlated with tumor de differentiation and unfavorable prognosis. BMP4 promoted HCC EMT and was correlated with OXA resistance. Blocking of BMP4 reversed EMT and increased OXA chemosensitivity in vitro and in vivo. ELK1, a transcription factor involved in EMT, was an important mediator of BMP4-induced OXA resistance in HCC. Blocking of MEK/ERK/ELK1 attenuated BMP4-induced EMT and enhanced OXA sensitivity. CONCLUSIONS: BMP4 induces EMT and OXA chemoresistance via MEK/ERK/ELK1 signaling pathway in HCC. BMP4 may be a valuable therapeutic target for HCC patients receiving OXA-based chemotherapy. PMID- 28987389 TI - Environmental tobacco smoke exposure and EGFR and ALK alterations in never smokers' lung cancer. Results from the LCRINS study. AB - Environmental tobacco smoke (ETS) exposure is a main risk factor of lung cancer in never smokers. Epidermal Growth Factor Receptor (EGFR) mutations and ALK translocations are more frequent in never smokers' lung cancer than in ever smokers. We performed a multicenter case-control study to assess if ETS exposure is associated with the presence of EGFR mutations and its types and if ALK translocations were related with ETS exposure. All patients were never smokers and had confirmed lung cancer diagnosis. ETS exposure during childhood showed a negative association on the probability of EGRF mutation though not significant. Exposure during adulthood, at home or at workplace, did not show any association with EGFR mutation. The mutation type L858R seemed the most associated with a lower probability of EGFR alterations for ETS exposure at home in adult life. There is no apparent association between ETS exposure and ALK translocation. These results might suggest that ETS exposure during childhood or at home in adult life could influence the EGFR mutations profile in lung cancer in never smokers, reducing the probability of presenting EFGR mutation. PMID- 28987390 TI - Molecular epidemiology of Clostridium difficile infection in a Brazilian cancer hospital. AB - Clostridium difficile is a Gram-positive spore forming anaerobic bacterium and the main cause of healthcare-associated diarrhea. This study aimed to perform the phenotypic characterization and molecular typing of Clostridium difficile isolates among patients at a cancer hospital in Brazil. During 18 months, 48 diarrheic fecal samples were collected, of these 48% were positive in either one or both of the performed tests: detection of toxins A/B and culture. Clostridium difficile was recovered from four samples (17%). All strains carried toxin A and B genes, and the isolates belonged to PCR-ribotype 014/020, PGFE-type NAP4 and toxinotype XVIII. On the other hand, one isolate belonged to a novel PCR ribotype, and PFGE-type, likewise to toxinotype IXb. The isolates showed susceptibility to metronidazole, vancomycin and moxifloxacin, and were resistant to ciprofloxacin. Finally, the findings indicate high positivity between the samples tested, suggesting an expressive importance of this infection, including detection of a novel ribotype/PFGE-type of Clostridium difficile, and show for the first time the detection of community-associated Clostridium difficile infection (CA-CDI) in these patients in Northeast Brazil. These data emphasize the importance to a better understanding of the epidemiological situation of this infection in Brazilian hospitals. PMID- 28987391 TI - Emergent lineages of mumps virus suggest the need for a polyvalent vaccine. AB - Mumps outbreaks among vaccinated patients have become increasingly common in recent years. While there are multiple conditions driving this re-emergence, convention has suggested that these outbreaks are associated with waning immunity rather than vaccine escape. Molecular evidence from both the ongoing American and Dutch outbreaks in conjunction with recent structural biology studies challenge this convention, and suggest that emergent lineages of mumps virus exhibit key differences in antigenic epitopes from the vaccine strain employed: Jeryl-Lynn 5. The American and Dutch 2016-2017 outbreak lineages were examined using computational biology through the lens of diversity in immunogenic epitopes. Findings are discussed and the laboratory evidence indicating neutralization of heterologous mumps strains by serum from vaccinated individuals is reviewed. Taken together, it is concluded that the number of heterologous epitopes occurring in mumps virus in conjunction with waning immunity is facilitating small outbreaks in vaccinated patients, and that consideration of a polyvalent mumps vaccine is warranted. PMID- 28987392 TI - Shunt Failure-Risk Factors and Outcomes: An Analysis of The Society of Thoracic Surgeons Congenital Heart Surgery Database. AB - BACKGROUND: Systemic-to-pulmonary shunt failure is a potentially catastrophic complication. We analyzed a large multicenter clinical registry to describe the prevalence and evaluate risk factors. METHODS: Infants (aged <=365 days) undergoing shunt operations (systemic artery-to-pulmonary artery or systemic ventricle-to-pulmonary artery) in The Society of Thoracic Surgeons Congenital Heart Surgery Database (STS-CHSD) from 2010 to 2015 were included. Multivariable logistic regression was used to evaluate risk factors for in-hospital shunt failure. Model covariates included patient characteristics, preoperative factors, procedural factors including shunt type, and center effects. Centers with more than 15% missing data for key covariates were excluded. RESULTS: Shunt operations were performed in 9,172 infants (118 centers). In-hospital shunt failure occurred in 674 (7.3%). In multivariable analysis, risk factors for in-hospital shunt failure included lower weight at operation (odds ratio [OR], 1.35; p = 0.001), preoperative hypercoagulable state (OR, 2.47; p = 0.031), and the presence of any other STS-CHSD preoperative risk factors (OR, 1.24; p = 0.038). Shunt failure was less likely with a systemic ventricle-to-pulmonary artery shunt than a systemic artery-to-pulmonary artery shunt (OR, 0.65; p = 0.020). Neither cardiopulmonary bypass nor single-ventricle diagnosis was a risk factor for shunt failure. Patients with in-hospital shunt failure had significantly higher rates of operative mortality (31.9% vs 11.1%, p < 0.001) and major morbidity (84.4% vs 29.4%, p < 0.001), and longer median postoperative length of stay among survivors (45 vs 22 days, p < 0.001). CONCLUSIONS: In-hospital shunt failure is common, and associated mortality risk is high. These data highlight at-risk patients and procedural cohorts that warrant expectant surveillance and may benefit from enhanced antithrombotic prophylaxis or other management strategies to reduce shunt failure. These findings may inform planning of future clinical trials. PMID- 28987393 TI - Perioperative Outcomes of Patients Undergoing Lobectomy on Clopidogrel. AB - BACKGROUND: Perioperative management of antiplatelet therapy for patients undergoing pulmonary resection must balance the risk of cardiovascular events with that of hemorrhage. An optimal approach has not been defined in this population. We sought to characterize outcomes of patients undergoing pulmonary lobectomy on antiplatelet therapy with clopidogrel. METHODS: A prospective institutional database was retrospectively reviewed to identify all patients undergoing pulmonary lobectomy from 2007 to 2015 who received perioperative clopidogrel. Patients were grouped according to the timing of clopidogrel discontinuation before operation: group I, 5 days or less; group II, 6 to 14 days; and group III, more than 14 days. Analyses were performed to assess the effect of timing of discontinuation on adverse events. RESULTS: Sixty-two patients were identified and included in the analysis. The indication for clopidogrel was coronary artery disease in 44 patients (71%), 35 (56%) of whom had prior stent placement. The overall incidences of transfusion and major cardiovascular events were 16% (10 of 62) and 6.5% (4 of 62), respectively. Non ST elevation myocardial infarctions occurred in 4 patients. Three were in patients with stents, all placed more than 1 year before the operation. There were no significant differences identified in estimated blood loss, operative duration, or perioperative deaths. CONCLUSIONS: No significant outcome differences in perioperative cardiovascular or hemorrhagic events were identified among the groups. Although these findings suggest that clopidogrel may be discontinued shortly before the operation with limited risk of bleeding, we also found that holding therapy for more than 14 days preoperatively may be safe in appropriately selected patients. PMID- 28987394 TI - Staphylococcus Aureus Prevention Strategies in Cardiac Surgery: A Cost Effectiveness Analysis. AB - BACKGROUND: Cardiac surgery patients colonized with Staphylococcus aureus have a greater risk of surgical site infection (SSI). The purpose of this study was to evaluate the cost-effectiveness of decolonization strategies to prevent SSIs. METHODS: We compared three decolonization strategies: universal decolonization (UD), all subjects treated; targeted decolonization (TD), only S aureus carriers treated; and no decolonization (ND). Decolonization included mupirocin, chlorhexidine, and vancomycin. We implemented a decision tree comparing the costs and quality-adjusted life-years (QALYs) of these strategies on SSI over a 1-year period for subjects undergoing coronary artery bypass graft surgery from a US health sector perspective. Deterministic and probabilistic sensitivity analyses were conducted to address the uncertainty in the variables. RESULTS: Universal decolonization was the dominant strategy because it resulted in reduced costs at near-equal QALYs compared with TD and ND. Compared with ND, UD decreased costs by $462 and increased QALYs by 0.002 per subject, whereas TD decreased costs by $205 and increased QALYs by 0.001 per subject. For 1,000 subjects, UD prevented 19 SSI and TD prevented 10 SSI compared with ND. Sensitivity analysis showed UD to be the most cost-effective strategy in more than 91% of simulations. For the 220,000 coronary artery bypass graft procedures performed yearly in the United States, UD would save $102 million whereas TD would save $45 million compared with ND. CONCLUSIONS: Universal decolonization outperforms other strategies. However, the potential costs savings of $57 million per 220,000 coronary artery bypass graft procedures comparing UD versus TD must be weighed against the potential risk of developing resistance associated with universal decolonization. PMID- 28987395 TI - Abciximab/Heparin Therapy for Left Ventricular Assist Device Implantation in Patients With Heparin-Induced Thrombocytopenia. AB - BACKGROUND: Optimal anticoagulation strategy remains uncertain in patients with heparin-induced thrombocytopenia (HIT) and undergoing left ventricular assist device (LVAD) implantation. We describe our protocol of abciximab and heparin in these patients. METHODS: Our protocol is to administer abciximab, 0.25 mg/kg loading dose, followed by continuous infusion of 0.125 MUg . kg-1 . min-1 throughout cardiopulmonary bypass. Full-dose heparin is then given with subsequent additional doses to maintain an activated clotting time of 400 seconds or longer. The abciximab infusion is stopped 15 minutes after heparin reversal with protamine, and platelets are transfused. RESULTS: Six patients underwent LVAD implantation with this protocol in our program. HIT was confirmed in 4 patients was suspected in 2, which was negative after the operation. One patient received a HeartMate XVE (Thoratec Corp, Pleasanton, CA) and the others received HeartMate II (Thoratec Corp). There were no thromboembolic complications. One patient required chest reexploration for bleeding and temporary right VAD support. Postoperative anticoagulation with argatroban was restarted on median postoperative day 3 (range, days 1 to 6) and warfarin was started on day 5 (range, days 3 to 12). Median postoperative intensive care unit stay was 9 days (range, 5 to 76 days), and hospital stay was 22 days (range, 18 to 132 days). After the initial LVAD implantation, 1 patient required HeartMate XVE LVAD exchange to HeartMate II and subsequent heart transplant, both of which were performed with the abciximab/heparin protocol. A HeartMate II device was explanted in another patient after myocardial recovery. The remaining 4 patients are alive on device support. CONCLUSIONS: This is the first report of a novel abciximab/heparin protocol for LVAD implantation in patients with HIT. The preliminary results suggest the feasibility and safety of this protocol. PMID- 28987396 TI - Use of Nicardipine After Cardiac Operations Is Safe in Children Regardless of Age. AB - BACKGROUND: Control of postoperative hypertension is central to the care of infants and children after cardiac operations. Continuous pharmacologic delivery affords the advantage of rapid onset and ease of titration. Although well established in older children and adults, calcium channel blockers are routinely avoided in children aged younger than 1 year secondary to concerns of safety and efficacy in the setting of sarcoplasmic reticulum development. Thus, the purpose of this study was to review a single-institution experience with nicardipine, a selective calcium channel blocker, in pediatric patients after cardiac operations. METHODS: Children undergoing cardiac operations at the University of Virginia from 2010 to 2015 were retrospectively reviewed after selection based on receipt of nicardipine for blood pressure management in the postoperative period. Demographic, operative, laboratory, and postoperative data were collected for adverse effect analysis and outcomes comparisons between infants aged younger than 6 months (group 1) and older than 6 months (group 2). RESULTS: During the study period, 68 children (group 1: n = 33 [48%]; group 2: n = 35 [52%]) received nicardipine after cardiac operations (0.5 to 1 MUg . kg-1 . min-1). Nicardipine was initiated at a mean of 6.6 +/- 13.1 hours postoperatively in group 1 and 5.4 +/- 7.8 hours in group 2. Nine patients (13%) demonstrated clinically significant hypotension necessitating dosing titration with no statistically significant differences between groups. No major adverse events occurred following nicardipine administration. CONCLUSIONS: Nicardipine is well tolerated after cardiac operations in children irrespective of age or underlying pathology. Thus, nicardipine should be considered as safe and effective in children of all ages for control of hypertension after cardiac operations. PMID- 28987398 TI - Normal Birth in a Post Truth world. PMID- 28987397 TI - Duration of Postoperative Mechanical Ventilation as a Quality Metric for Pediatric Cardiac Surgical Programs. AB - BACKGROUND: Few metrics exist to assess quality of care at pediatric cardiac surgical programs, limiting opportunities for benchmarking and quality improvement. Postoperative duration of mechanical ventilation (POMV) may be an important quality metric because of its association with complications and resource utilization. In this study we modelled case-mix-adjusted POMV duration and explored hospital performance across POMV metrics. METHODS: This study used the Pediatric Cardiac Critical Care Consortium clinical registry to analyze 4,739 hospitalizations from 15 hospitals (October 2013 to August 2015). All patients admitted to pediatric cardiac intensive care units after an index cardiac operation were included. We fitted a model to predict duration of POMV accounting for patient characteristics. Robust estimates of SEs were obtained using bootstrap resampling. We created performance metrics based on observed-to expected (O/E) POMV to compare hospitals. RESULTS: Overall, 3,108 patients (65.6%) received POMV; the remainder were extubated intraoperatively. Our model was well calibrated across groups; neonatal age had the largest effect on predicted POMV. These comparisons suggested clinically and statistically important variation in POMV duration across centers with a threefold difference observed in O/E ratios (0.6 to 1.7). We identified 1 hospital with better-than expected and 3 hospitals with worse-than-expected performance (p < 0.05) based on the O/E ratio. CONCLUSIONS: We developed a novel case-mix-adjusted model to predict POMV duration after congenital heart operations. We report variation across hospitals on metrics of O/E duration of POMV that may be suitable for benchmarking quality of care. Identifying high-performing centers and practices that safely limit the duration of POMV could stimulate quality improvement efforts. PMID- 28987399 TI - Review of difficult airway management in thoracic surgery. AB - The management of difficult airway (DA) in thoracic surgery is more difficult due to the need for lung separation or isolation and frequent presence of associated upper and lower airway problems. We performed an article review analysing 818 papers published with clinical evidence indexed in Pubmed that allowed us to develop an algorithm. The best airway management in predicted DA is tracheal intubation and independent bronchial blockers guided by fibroscopy maintaining spontaneous ventilation. For unpredicted DA, the use of videolaryngoscopes is recommended initially, and adequate neuromuscular relaxation (rocuronium/sugammadex), among other maneuvers. In both cases, double lumen tubes should be reserved for when lung separation is absolutely indicated. Finally, extubation should be a time of maximum care and be performed according to the safety measures of the Difficult Arway Society. PMID- 28987400 TI - Minimum Distance of Suture Anchors Used for Rotator Cuff Repair Without Decreasing the Pullout Strength: A Biomechanical Study. AB - PURPOSE: To investigate the minimum distance between the anchors without decreasing the pullout strength using the polyurethane foams and the porcine bones. METHODS: Metal screw-type anchors and PEEK (polyether ether ketone) coil type anchors were used. Two same-type suture anchors were placed into the polyurethane foams and porcine bones. The polyurethane foams were 3 different densities simulating severe osteoporosis, osteoporosis, and normal bone. The distances between the centers of anchors were set at 4, 6, 8, and 10 mm. The pair of anchors were loaded to failure if they had not been pulled out after cyclic loading from 50 to 200 N, 10 cycles per each 50-N increment. Mode of failure, ultimate load to failure, displacement of the anchor, and number of cycles completed were recorded. RESULTS: In all polyurethane foams of 3 different densities with use of metal screw-type anchors, the 4-mm group demonstrated a significantly lower ultimate load to failure compared with the 6-, 8-, and 10-mm groups (P < .01). There were no significant differences in the load to failure among the 6-, 8-, and 10-mm groups. Porcine bone or PEEK coil-type anchor showed results similar to those of the metal screw-type anchors. CONCLUSION: For the 2 tested anchors, the minimum distance between the anchors without decreasing the pullout strength was 6 mm (center to center) regardless of bone density in a biomechanical study. CLINICAL RELEVANCE: Although it has been thought that the minimum distance between the anchors without decreasing the pullout strength was 1 cm (center to center), our data showed that it was 6 mm. PMID- 28987401 TI - PM2.5 exposure stimulates COX-2-mediated excitatory synaptic transmission via ROS NF-kappaB pathway. AB - Long-term exposure to fine particulate matter (PM2.5) has been reported to be closely associated with the neuroinflammation and synaptic dysfunction, but the mechanisms underlying the process remain unclear. Cyclooxygenase-2 (COX-2) is a key player in neuroinflammation, and has been also implicated in the glutamatergic excitotoxicity and synaptic plasticity. Thus, we hypothesized that COX-2 was involved in PM2.5-promoted neuroinflammation and synaptic dysfunction. Our results revealed that PM2.5 elevated COX-2 expression in primary cultured hippocampal neurons and increased the amplitude of field excitatory postsynaptic potentials (fEPSPs) in hippocampal brain slices. And the administration of NS398 (a COX-2 inhibitor) prevented the increased fEPSPs. PM2.5 also induced intracellular reactive oxygen species (ROS) generation accompanied with glutathione (GSH) depletion and the loss of mitochondrial membrane potential (MMP), and the ROS inhibitor, N-acetyl-L-cystein (NAC) suppressed the COX-2 overexpression and the increased fEPSPs. Furthermore, the nuclear factor kappa B (NF-kappaB) was involved in ROS-induced COX-2 and fEPSP in response to PM2.5 exposure. These findings indicated that PM2.5 activated COX-2 expression and enhanced the synaptic transmission through ROS-NF-kappaB pathway, and provided possible biomarkers and specific interventions for PM2.5-induced neurological damage. PMID- 28987402 TI - Fluorine-doped carbon nanotubes as an efficient metal-free catalyst for destruction of organic pollutants in catalytic ozonation. AB - Metal-free carbon materials have been presented to be potential alternatives to metal-based catalysts for heterogeneous catalytic ozonation, yet the catalytic performance still needs to be enhanced. Doping carbon with non-metallic heteroatoms (e.g., N, B, and F) could alter the electronic structure and electrochemical properties of original carbon materials, has been considered to be an effective method for improving the catalytic activity of carbon materials. Herein, fluorine-doped carbon nanotubes (F-CNTs) were synthesized via a facile method and characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and Raman spectroscopy. The as-synthesized F-CNTs exhibited notably enhanced catalytic activity towards catalytic ozonation for the degradation of organic pollutants. The oxalic acid removal efficiency of optimized F-CNTs was approximately two times as much as that of pristine CNTs, and even exceeded those of four conventional metal-based catalysts (ZnO, Al2O3, Fe2O3, and MnO2). The XPS and Raman studies confirmed that the covalent CF bonds were formed at the sp3 C sites instead of sp2 C sites on CNTs, not only resulting in high positive charge density of C atoms adjacent to F atoms, but remaining the delocalized pi-system with intact carbon structure of F-CNTs, which then favored the conversion of ozone molecules (O3) into reactive oxygen species (ROS) and contributed to the high oxalic acid removal efficiency. Furthermore, electron spin resonance (ESR) studies revealed that superoxide radicals (O2-) and singlet oxygen (1O2) might be the dominant ROS that responsible for the degradation of oxalic acid in these catalytic systems. PMID- 28987403 TI - Effects of prescribed fire and post-fire rainfall on mercury mobilization and subsequent contamination assessment in a legacy mine site in Victoria, Australia. AB - Prescribed fire conducted in fire-prone areas is a cost-effective choice for forest management, but it also affects many of the physicochemical and bio geological properties of the forest soil, in a similar manner to wild fires. The aim of this study is to investigate the nature of the mercury mobilization after a prescribed fire and the subsequent temporal changes in concentration. A prescribed fire was conducted in a legacy mine site in Central Victoria, Australia, in late August 2015 and soil sample collection and analyses were carried out two days before and two days after the fire, followed by collection at the end of each season and after an intense rainfall event in September 2016. Results revealed the occurrence of mercury volatilization (8.3-97%) during the fire, and the mercury concentration displayed a significant difference (p < 0.05) before and immediately after the fire. Integrated assessment with number of pollution indices has shown that the study site is extremely contaminated with mercury during all the sampling events, and this poses a serious ecological risk due to the health impacts of mercury on human and ecosystems. In times of climate fluctuation with concomitant increase in forest fire (including prescribed fire), and subsequent precipitation and runoff, the potential for an increased amount of mercury being mobilized is of heighted significance. Therefore, it is recommended that prescribed fire should be cautiously considered as a forest management strategy in any mercury affected landscapes. PMID- 28987404 TI - Comparative transcriptome analysis of duckweed (Landoltia punctata) in response to cadmium provides insights into molecular mechanisms underlying hyperaccumulation. AB - Cadmium (Cd) is a detrimental environmental pollutant. Duckweeds have been considered promising candidates for Cd phytoremediation. Although many physiological studies have been conducted, the molecular mechanisms underlying Cd hyperaccumulation in duckweeds are largely unknown. In this study, clone 6001 of Landoltia punctata, which showed high Cd tolerance, was obtained by large-scale screening of over 200 duckweed clones. Subsequently, its growth, Cd flux, Cd accumulation, and Cd distribution characteristics were investigated. To further explore the global molecular mechanism, a comprehensive transcriptome analysis was performed. For RNA-Seq, samples were treated with 20 MUM CdCl2 for 0, 1, 3, and 6 days. In total, 9,461, 9,847, and 9615 differentially expressed unigenes (DEGs) were discovered between Cd-treated and control (0 day) samples. DEG clustering and enrichment analysis identified several biological processes for coping with Cd stress. Genes involved in DNA repair acted as an early response to Cd, while RNA and protein metabolism would be likely to respond as well. Furthermore, the carbohydrate metabolic flux tended to be modulated in response to Cd stress, and upregulated genes involved in sulfur and ROS metabolism might cause high Cd tolerance. Vacuolar sequestration most likely played an important role in Cd detoxification in L. punctata 6001. These novel findings provided important clues for molecular assisted screening and breeding of Cd hyperaccumulating cultivars for phytoremediation. PMID- 28987405 TI - Combined effect of temperature and nutritional regime on the elimination of the lipophilic toxin okadaic acid in the naturally contaminated wedge shell Donax trunculus. AB - The influence of nutritional regime and water temperature on depuration rates of OA-group toxins in the wedge shell Donax trunculus was examined by exposing naturally contaminated specimens to three nutritional regimes (microalgae, commercial paste of microalgae, and starvation) for 14 days at 16 degrees C and 20 degrees C. Total OA was quantified in the whole soft tissues of the individuals collected in days 2, 4, 6, 8, 10, 12 and 14. Mortality, dry weight, condition index, gross biochemical composition and gametogenic stages were surveyed. Low variation of glycogen and carbohydrates during the experiments suggest that wedge shells were under non-dramatic stress conditions. Wedge shells fed with non-toxic diets showed similar depuration rates being 15 and 38% higher than in starvation, at 16 and 20 degrees C, respectively. Depuration rates under non-toxic diets at 20 degrees C were 71% higher than at 16 degrees C. These results highlight the influence of water temperature on the depuration rate of total OA accumulated by D. trunculus, even when the increase is of only 4 degrees C, as commonly observed in week time scales in the southern Portuguese coastal waters. These results open the possibility of a faster release of OA in harvested wedge shells translocated to depuration systems when under a slight increase of water temperature. PMID- 28987406 TI - Ametryn removal by Metarhizium brunneum: Biodegradation pathway proposal and metabolic background revealed. AB - Ametryn is a representative of a class of s-triazine herbicides absorbed by plant roots and leaves and characterized as a photosynthesis inhibitor. It is still in use in some countries in the farming of pineapples, soybean, corn, cotton, sugar cane or bananas; however, due to the adverse effects of s-triazine herbicides on living organisms use of these pesticides in the European Union has been banned. In the current study, we characterized the biodegradation of ametryn (100 mg L-1) by entomopathogenic fungal cosmopolite Metarhizium brunneum. Ametryn significantly inhibited the growth and glucose uptake in fungal cultures. The concentration of the xenobiotic drops to 87.75 mg L-1 at the end of culturing and the biodegradation process leads to formation of four metabolites: 2-hydroxy atrazine, ethyl hydroxylated ametryn, S-demethylated ametryn and deethylametryn. Inhibited growth is reflected in the metabolomics data, where significant differences in concentrations of L-proline, gamma-aminobutyric acid, L-glutamine, 4-hydroxyproline, L-glutamic acid, ornithine and L-arginine were observed in the presence of the xenobiotic when compared to control cultures. The metabolomics data demonstrated that the presence of ametryn in the fungal culture induced oxidative stress and serious disruptions of the carbon and nitrogen metabolism. Our results provide deeper insights into the microorganism strategy for xenobiotic biodegradation which may result in future enhancements to ametryn removal by the tested strain. PMID- 28987407 TI - Electron beam irradiation induced degradation of antidepressant drug fluoxetine in water matrices. AB - With the development of psychiatric disorder in the current society, abuse of antidepressant drug fluoxetine (FLX) has made such compound an emerging contaminant in natural waters, and causes endocrine systems disturbance on some aquatic species. Herein, an efficient advanced oxidation process (AOP), electron beam irradiation was carried out to investigate the decomposition characteristics of such novel environmental pollutant, including the effects of initial concentration, pH, radical scavengers and anions. The results showed that FLX degradation followed pseudo-first-order kinetics. The degradation rate and dose constant decreased with increasing initial FLX concentration; and G-values elevated with the increase of initial concentration but reduced with increase of absorbed dose. Acidic condition was more conducive to FLX destruction than neutral and alkaline. The radical scavenger experiments indicated OH was the main reactive species for the decomposition of FLX, while the reductive species e-aq and H played an adjuvant role. The presence of anions slightly decreased or even no impact on FLX degradation rate. Various water matrices influenced degradation processes of FLX. Experimental results suggested radiolytic degradation showed the best performance in pure water rather than natural water no matter with filtration or not. Moreover, with the occurrence of defluorination and dealkylation during degradation process, some organic and inorganic intermediates were detected, and the possible degradation mechanisms and pathways of FLX were proposed. PMID- 28987408 TI - Perfluorohexadecanoic acid increases paracellular permeability in endothelial cells through the activation of plasma kallikrein-kinin system. AB - Per- and polyfluoroalkyl substances (PFASs) are ubiquitous and high persistent in human blood, thus potentially inducing a myriad of deleterious consequences. Plasma kallikrein-kinin system (KKS), which physiologically regulates vascular permeability, is vulnerable to exogenous stimulators, like PFASs with long-chain alkyl backbone substituted by electronegative fluorine. The study on the interactions of PFASs with the KKS and the subsequent effects on vascular permeability would be helpful to illustrate how the chemicals penetrate the biological vascular barriers to reach different tissues. In present study, three representative PFASs, including perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA) and perfluorohexadecanoic acid (PFHxDA), were investigated for their effects on the activation of the KKS, paracellular permeability in human retina endothelial cells (HRECs) and integrity of the adherens junctions. In contrast to either PFOS or PFOA, PFHxDA efficiently triggered KKS activation in a concentration-dependent manner based on protease activity assays. The plasma activated by PFHxDA significantly increased paracellular permeability of HRECs through the degradation of adherens junctions. As evidenced by the antagonistic effect of aprotinin, PFHxDA-involved effects on vascular permeability were mediated by KKS activation. The results herein firstly revealed the mechanistic pathway for PFHxDA induced effects on vascular endothelial cells. Regarding the possible structure-related activities of the chemicals, this finding would be of great help in the risk assessment of PFASs. PMID- 28987409 TI - Enhance wastewater biological treatment through the bacteria induced graphene oxide hydrogel. AB - The interaction between bacteria and graphene-family materials like pristine graphene, graphene oxide (GO) and reduced graphene oxide (rGO) is such an elusive issue that its implication in environmental biotechnology is unclear. Herein, two kinds of self-assembled bio-rGO-hydrogels (BGHs) were prepared by cultivating specific Shewanella sp. strains with GO solution for the first time. The microscopic examination by SEM, TEM and CLSM indicated a porous 3D structure of BGHs, in which live bacteria firmly anchored and extracellular polymeric substances (EPS) abundantly distributed. Spectra of XRD, FTIR, XPS and Raman further proved that GO was reduced to rGO by bacteria along with the gelation process, which suggests a potential green technique to produce graphene. Based on the characterization results, four mechanisms for the BGH formation were proposed, i.e., stacking, bridging, rolling and cross-linking of rGO sheets, through the synergistic effect of activities and EPS from special bacteria. More importantly, the BGHs obtained in this study were found able to achieve unique cleanup performance that the counterpart free bacteria could not fulfill, as exemplified in Congo red decolorization and Cr(VI) bioreduction. These findings therefore enlighten a prospective application of graphene materials for the biological treatment of wastewaters in the future. PMID- 28987410 TI - Variable dual carbon-bromine stable isotope fractionation during enzyme-catalyzed reductive dehalogenation of brominated ethenes. AB - The potential of compound-specific stable isotope analysis (CSIA) to characterize biotransformation of brominated organic compounds (BOCs) was assessed and compared to chlorinated analogues. Sulfurospirillum multivorans and Desulfitobacterium hafniense PCE-S catalyzed the dehalogenation of tribromoethene (TBE) to either vinyl bromide (VB) or ethene, respectively. Significantly lower isotope fractionation was observed for TBE dehalogenation by S. multivorans (epsilonC = -1.3 +/- 0.20/00) compared to D. hafniense (epsilonC = -7.7 +/- 1.50/00). However, higher fractionation was observed for dibromoethene (DBE) dehalogenation by S. multivorans (epsilonC = -16.8 +/- 1.80/00 and -21.2 +/- 1.60/00 for trans- and cis-1,2- (DBE) respectively), compared to D. hafniense PCE S (epsilonC = -9.5 +/- 1.20/00 and -14.5 +/- 0.70/00 for trans-1,2-DBE and cis 1,2-DBE, respectively). Significant, but similar, bromine fractionation was observed for for S. multivorans (epsilonBr = -0.53 +/- 0.150/00, -1.03 +/- 0.260/00, and -1.18 +/- 0.130/00 for trans-1,2-DBE, cis-1,2-DBE and TBE, respectively) and D. hafniense PCE-S (epsilonBr = -0.97 +/- 0.280/00, -1.16 +/- 0.360/00, and -1.34 +/- 0.320/00 for cis-1,2-DBE, TBE and trans-1,2-DBE, respectively). Variable CBr dual-element slopes were estimated at Lambda (epsilonC/epsilonBr) = 1.03 +/- 0.2, 17.9 +/- 5.8, and 29.9 +/- 11.0 for S. multivorans debrominating TBE, cis-1,2-DBE and trans-1,2-DBE, respectively, and at 7.14 +/- 1.6, 8.27 +/- 3.7, and 8.92 +/- 2.4 for D. hafniense PCE-S debrominating trans-1,2-DBE, TBE and cis-1,2-DBE, respectively. A high variability in isotope fractionation, which was substrate property related, was observed for S. multivorans but not D. hafniense, similar as observed for chlorinated ethenes, and may be due to rate-limiting steps preceding the bond cleavage or differences in the reaction mechanism. Overall, significant isotope fractionation was observed and, therefore, CSIA can be applied to monitor the fate of brominated ethenes in the environment. Isotope effects differences, however, are not systematically comparable to chlorinated ethenes. PMID- 28987411 TI - Why the VA matters: Resident education, research and patient care. AB - The Veterans' Health Administration (VHA) has had a long and storied relationship with academic medicine and particularly academic surgery throughout its history. Since the initial inception of the Veterans' Health Administration in 1946 there have been relationships between medical schools and the VHA to provide care to our veterans as well as provide a fertile training environment for the residents that will enhance their overall training experience and prepare them to the provide health care for the nation as a whole. At this point in our history that relationship is in jeopardy. The problems facing the Veterans' Health Administration are well known and seemingly are proving to be an insurmountable obstacle for continuation of this relationship. It is my intention in this lecture honoring Dr. Organ, who was committed to surgical education as well as the surgical care of our veterans to demonstrate why the Veterans' Health Administration is more important than ever to the well-being of our residents and graduate medical education as a whole. PMID- 28987412 TI - Discussion of: "Day versus night laparoscopic cholecystectomy for acute cholecystitis: A comparison of outcomes and cost". PMID- 28987414 TI - Discussion of: "Is it necessary to perform full pathologic review of all gastric remnants following sleeve gastrectomy?" PMID- 28987413 TI - PTSD and surgical residents: Everybody hurts... sometimes. AB - BACKGROUND: We aim to evaluate the prevalence of PTSD, its association with physician burnout, and risk factors for PTSD among surgical residents. METHODS: A cross-sectional national survey of surgical residents was conducted screening for PTSD. Causative traumatic stressors were queried, and thirty-one potential risk factors for PTSD were evaluated. RESULTS: A positive PTSD screen (PTSD+) was found in 22% of 582 surgical residents, and an additional 35% were "at risk" for PTSD. Traumatic experiences occurred most commonly as a PGY1, and the most common stressor was bullying. An increase in average hours of work per week (p < 0.001), a high-risk screen for PBO (p < 0.001), and feeling unhealthy (p = 0.001) were associated with an increasing prevalence of screening PTSD+. CONCLUSIONS: The prevalence of screening PTSD+ among surgical residents (22%) was more than three times the general population. Increased work-hours, a high-risk PBO screen, and reduced resident wellness were associated with screening PTSD+. PMID- 28987415 TI - Discussion of: "Does lymph node status influence adjuvant therapy decision-making in women 70 years of age or older with clinically node negative hormone receptor positive breast cancer?" PMID- 28987416 TI - Growth-related changes in non-essential and essential metals in the liver of star spotted smooth-hounds (dogfish) Mustelus manazo from the northern region of Japan. AB - We analyzed Cd, Hg, Zn, Cu, Mn and Fe concentrations in liver samples from male and female star-spotted smooth-hounds at various life stages. Male sharks of this species are known to reach their maximum body length (BL) more quickly than females, while females are known to mature later and live longer than males. Hepatic Cd and Hg concentrations in males and females markedly increased after maturation, but these increases proceeded earlier in males than in females. Hepatic Zn and Cu concentrations decreased during the growth stage of males and females, and thereafter increased concomitantly with increases of Cd and Hg burdens, forming a U-shaped curve over their lifespan, and the BL at which the lowest concentrations of Zn and Cu were observed was smaller in males than in females. These gender-related differences in those metals could reflect the faster growth and earlier cessation of growth in males. PMID- 28987417 TI - [Radicular pain caused by Schmorl's node: a case report]. AB - Schmorl's node is focal herniation of intervertebral disc through the end plate into the vertebral body. Most of the established Schmorl's nodes are quiescent. However, disc herniation into the vertebral marrow can cause low back pain by irritating a nociceptive system. Schmorl's node induced radicular pain is very rare condition. Some cases of Schmorl's node which generated low back pain or radicular pain were treated by surgical methods. In this article, authors reported a rare case of a patient with radicular pain cause by Schmorl's node located inferior surface of the 5th lumbar spine. The radicular pain was alleviated by serial 5th lumbar transforamnial epidural blocks. Transforamnial epidural block is suggested as first conservative option to treat radicular pain due to herniation of intervertebral disc. Therefore, non-surgical treatment such as transforamnial epidural block can be considered first treatment option of radicular pain caused by Schmorl's node. PMID- 28987418 TI - A Case of an Unexpected Cholangiopancreatography With Choledochocele. PMID- 28987419 TI - Endoscopic Ultrasound-Guided Pancreatic Cyst Ablation: More Peril Than Promise? PMID- 28987420 TI - How to Balance Clinical Work and Research in the Current Era of Academic Medicine. PMID- 28987421 TI - Do Liver Mucosa-Associated Invariant T Cells Delay Hepatitis C Progression, or Are They Innocent Bystanders? PMID- 28987422 TI - Colorectal Cancer Screening: Money Isn't Everything . . . But It Helps! PMID- 28987425 TI - Thoracic Aortic Syndromes. AB - Aortic dissection (AD) is a lethal, treatable disruption of the aortic vessel wall. It often presents without classic features, mimicking symptoms of other conditions, and diagnosis is often delayed. Established high-risk markers of AD should be sought and indicate advanced aortic imaging with CT, MRI, or TEE. Treatment is immediate surgical evaluation, aggressive symptom relief, and reduction of the force of blood against the aortic wall by control of heart rate, followed by blood pressure. PMID- 28987424 TI - Strategies to obtain multiple recombinant modified vaccinia Ankara vectors. Applications to influenza vaccines. AB - As a vaccination vector, MVA has been widely investigated both in animal models and humans. The construction of recombinant MVA (rMVA) relies on homologous recombination between an acceptor virus and a donor plasmid in infected/transfected permissive cells. Our construction strategy "Red-to-Green gene swapping" - based on the exchange of two fluorescent markers within the flanking regions of MVA deletion DeltaIII, coupled to fluorescence activated cell sorting - is here extended to a second insertion site, within the flanking regions of MVA deletion DeltaVI. Exploiting this strategy, both double and triple rMVA were constructed, expressing as transgenes the influenza A proteins HA, NP, M1, and PB1. Upon validation of the harbored transgenes co-expression, double and triple recombinants rMVA(DeltaIII)-NP-P2A-M1 and rMVA(DeltaIII)-NP-P2A-M1 (DeltaVI)-PB1 were assayed for in vivo immunogenicity and protection against lethal challenge. In vivo responses were identical to those obtained with the reported combinations of single recombinants, supporting the feasibility and reliability of the present improvement and the extension of Red-to-Green gene swapping to insertion sites other than DeltaIII. PMID- 28987426 TI - Extracranial Cervical Artery Dissections. AB - Cervical artery dissections (CeAD) include both internal carotid and vertebral artery dissections. They are rare but important causes of stroke, especially in younger patients. CeAD should be considered in patients with strokelike symptoms, a new-onset headache and/or neck pain, and/or other risk factors. Early imaging with computed tomography (CT) or magnetic resonance imaging (MRI) is key to making the diagnosis. Treatment may vary depending on the extent of the dissection, timing of the dissection, and other comorbidities. The overall prognosis is good, but does depend on the initial severity of symptoms. PMID- 28987423 TI - MicroRNA 122, Regulated by GRLH2, Protects Livers of Mice and Patients From Ethanol-Induced Liver Disease. AB - BACKGROUND & AIMS: Chronic, excessive alcohol consumption leads to alcoholic liver disease (ALD) characterized by steatosis, inflammation, and eventually cirrhosis. The hepatocyte specific microRNA 122 (MIR122) regulates hepatocyte differentiation and metabolism. We investigated whether an alcohol-induced decrease in level of MIR122 contributes to development of ALD. METHODS: We obtained liver samples from 12 patients with ALD and cirrhosis and 9 healthy individuals (controls) and analyzed them by histology and immunohistochemistry. C57Bl/6 mice were placed on a Lieber-DeCarli liquid diet, in which they were fed ethanol for 8 weeks, as a model of ALD, or a control diet. These mice were also given injections of CCl4, to increase liver fibrosis, for 8 weeks. On day 28, mice with ethanol-induced liver disease and advanced fibrosis, and controls, were given injections of recombinant adeno-associated virus 8 vector that expressed the primary miR-122 transcript (pri-MIR122, to overexpress MIR122 in hepatocytes) or vector (control). Two weeks before ethanol feeding, some mice were given injections of a vector that expressed an anti-MIR122, to knock down its expression. Serum and liver tissues were collected; hepatocytes and liver mononuclear cells were analyzed by histology, immunoblots, and confocal microscopy. We performed in silico analyses to identify targets of MIR122 and chromatin immunoprecipitation quantitative polymerase chain reaction analyses in Huh-7 cells. RESULTS: Levels of MIR122 were decreased in liver samples from patients with ALD and mice on the Lieber-DeCarli diet, compared with controls. Transgenic expression of MIR122 in hepatocytes of mice with ethanol-induced liver disease and advanced fibrosis significantly reduced serum levels of alanine aminotransferase (ALT) and liver steatosis and fibrosis, compared with mice given injections of the control vector. Ethanol feeding reduced expression of pri MIR122 by increasing expression of the spliced form of the transcription factor grainyhead like transcription factor 2 (GRHL2) in liver tissues from mice. Levels of GRHL2 also were increased in liver tissues from patients with ALD, compared with controls; increases correlated with decreases in levels of MIR122 in human liver. Mice given injections of the anti-MIR122 before ethanol feeding had increased steatosis, inflammation, and serum levels of alanine aminotransferase compared with mice given a control vector. Levels of hypoxia-inducible factor 1 alpha (HIF1alpha) mRNA, a target of MIR122, were increased in liver tissues from patients and mice with ALD, compared with controls. Mice with hepatocyte-specific disruption of Hif1alpha developed less-severe liver injury following administration of ethanol, injection of anti-MIR122, or both. CONCLUSIONS: Levels of MIR122 decrease in livers from patients with ALD and mice with ethanol-induced liver disease, compared with controls. Transcription of MIR122 is inhibited by GRHL2, which is increased in livers of mice and patients with ALD. Expression of an anti-MIR122 worsened the severity of liver damage following ethanol feeding in mice. MIR122 appears to protect the liver from ethanol-induced damage by reducing levels of HIF1alpha. These processes might be manipulated to reduce the severity of ALD in patients. PMID- 28987427 TI - Deep Venous Thrombosis. AB - Deep venous thrombosis (DVT) is a frequently encountered condition that is often diagnosed and treated in the outpatient setting. Risk stratification is helpful and recommended in the evaluation of DVT. An evidence-based diagnostic approach is discussed here. Once diagnosed, the mainstay of DVT treatment is anticoagulation. The specific type and duration of anticoagulation depend upon the suspected etiology of the venous thromboembolism, as well as risks of bleeding and other patient comorbidities. Both specific details and a standardized approach to this vast treatment landscape are presented. PMID- 28987428 TI - Vascular Access Complications: An Emergency Medicine Approach. AB - Millions of central venous and arterial catheters are placed across the United States annually as mechanisms of obtaining advanced hemodynamic monitoring and facilitating acute resuscitation. Although presumably life saving or sustaining in many circumstances, current literature identifies the preprocedural and postprocedural complications of infection, thrombosis, embolism, and iatrogenic injury as resulting in patient morbidity and mortality. Today, through the application of aseptic technique, performance of operator training, and the utilization of ultrasound, emergency physicians may limit vascular access complications and improve patient outcomes. PMID- 28987429 TI - Penetrating Vascular Injury: Diagnosis and Management Updates. AB - Penetrating vascular injury is becoming increasingly common in the United States and abroad. Much of the current research and treatment is derived from wartime and translation to the civilian sector has been lacking. Penetrating vascular injury can be classified as extremity, junctional, or noncompressible. Diagnosis can be obvious but at other times subtle and difficult to diagnose. Although there are numerous modalities, computed tomography angiography is the diagnostic study of choice. It is hoped that care will be improved by using an algorithmic approach integrating experience from military and civilian research. PMID- 28987430 TI - Subarachnoid Hemorrhage: Updates in Diagnosis and Management. AB - Subarachnoid hemorrhage (SAH) is a neurologic emergency due to bleeding into the subarachnoid space. Mortality can reach 50%. The clinical presentation is most often in the form of headache, classically defined as maximal at onset and worst of life. The most common cause is traumatic; approximately 80% of nontraumatic SAH are due to aneurysmal rupture, with the remainder from idiopathic peri mesencephalic hemorrhage or other less common causes. Noncontrast brain computed tomography (CT) performed within 6 hours of symptom onset has sensitivity approaching 100%. Lumbar puncture may be considered after this period for definitive diagnosis if initial CT is normal. PMID- 28987431 TI - Spontaneous Intracerebral Hemorrhage. AB - Although commonly arising from poorly controlled hypertension, spontaneous intracerebral hemorrhage may occur secondary to several other etiologies. Clinical presentation to the emergency department ranges from headache with vomiting to coma. In addition to managing the ABCs, the crux of emergency management lies in stopping hematoma expansion and other complications to prevent clinical deterioration. This may be achieved primarily through anticoagulation reversal, blood pressure, empiric management of intracranial pressure, and early neurosurgical consultation for posterior fossa hemorrhage. Patients must be admitted to intensive care. The effects of intracerebral hemorrhage are potentially devastating with very poor prognoses for functional outcome and mortality. PMID- 28987432 TI - Abdominal Aortic Emergencies. AB - This article discusses abdominal aortic emergencies. There is a common thread of risk factors and causes of these diseases, including age, male gender, hypertension, dyslipidemia, and connective tissue disorders. The most common presenting symptom of these disorders is pain, usually in the chest, flank, abdomen, or back. Computed tomography scan is the gold standard for diagnosis of pathologic conditions of the aorta in the hemodynamically stable patient. Treatment consists of a combination of blood pressure and heart rate control and, in many cases, emergent surgical intervention. PMID- 28987433 TI - Cerebral Venous Thrombosis: A Challenging Neurologic Diagnosis. AB - Headache is a common emergency department chief complaint. Although most are benign, emergency physicians must rapidly identify and manage the uncommon, sometimes subtle, presentation of headache from a life-threatening cause. Cerebral venous thrombosis imparts significant morbidity and mortality, and can be a challenging diagnosis. It most commonly occurs in those under 50 years of age with thrombosis of the cerebral veins/sinuses. Diagnosis is frequently delayed. The disease can present with 1 or more clinical syndromes, including intracranial hypertension with headaches, focal neurologic deficits, seizures, and encephalopathy. Diagnosis requires imaging. Treatment includes stabilization, management of complications, and anticoagulation. PMID- 28987434 TI - Mesenteric Ischemia: A Deadly Miss. AB - Mesenteric ischemia has 4 etiologies: arterial embolus, arterial thrombosis, venous thrombosis, and nonocclusive. No history or physical examination finding can definitively diagnose the condition. A wide variety of presentations occur. Pain out of proportion and gut emptying may occur early, with minimal tenderness. Once transmural infarction occurs, peritoneal findings and tenderness to palpation may occur. Physicians must be suspicious of pain out of proportion and scrutinize risk factors. Computed tomography angiography is the best imaging modality. Treatment requires surgery and interventional radiology consultation, intravenous antibiotics and fluids, and anticoagulation. The physician at the bedside is the best diagnostic tool. PMID- 28987435 TI - Acute Limb Ischemia: An Emergency Medicine Approach. AB - Acute limb ischemia is a medical emergency with significant morbidity and mortality. Rapid diagnosis is required because it is a time-sensitive condition. Timely treatment is necessary to restore blood flow to the extremity and prevent complications. The differential diagnosis of acute limb ischemia is broad. Classification of severity of acute limb ischemia is based on clinical variables. A suspicion of acute ischemia based on history and physical examination warrants heparin administration and vascular surgery consultation. The decision for endovascular thrombolysis or standard surgery depends on etiology, duration, and location of vascular occlusion. This review evaluates the diagnostic approach and management for acute limb ischemia. PMID- 28987436 TI - Ischemic Stroke: Advances in Diagnosis and Management. AB - Acute ischemic stroke carries the risk of morbidity and mortality. Since the advent of intravenous thrombolysis, there have been improvements in stroke care and functional outcomes. Studies of populations once excluded from thrombolysis have begun to elucidate candidates who might benefit and thus should be engaged in the process of shared decision-making. Imaging is evolving to better target the ischemic penumbra salvageable with prompt reperfusion. Availability and use of computed tomography angiography identifies large-vessel occlusions, and new generation endovascular therapy devices are improving outcomes in these patients. With this progress in stroke treatment, risk stratification tools and shared decision-making are fundamental. PMID- 28987437 TI - Vascular Emergencies. PMID- 28987438 TI - Time-Critical Vascular Disasters. PMID- 28987439 TI - Evaluation of T and B memory cell responses elicited by the pandemic H1N1 vaccine in HIV-infected and HIV-uninfected individuals. AB - BACKGROUND: This study was to compare B and T memory cells elicited by a single dose monovalent 2009 influenza A (H1N1) vaccine (strain A/California/7/2009 H1N1) in HIV+ and HIV- groups, and to analyze the impact of the prior seasonal vaccines to the immunogenicity of this vaccine. METHODS: Blood samples were collected before vaccination (day 0) and at days 28 and 180. Participants were categorized into HIV-/LAIV, HIV-/TIV and HIV+/TIV subgroups according to the trivalent live attenuated or inactivated (LAIV or TIV) seasonal influenza vaccines they received previously. The IgG+ memory B cells (BMem) and IFNgamma+ T cells were measured against antigens including the H1N1 vaccine, the hemagglutinin (HA) and neuraminidase (NA) proteins or peptide pools of the pandemic and the seasonal H1N1 strains, respectively. RESULTS: Overall BMem responses increased significantly at day 28 but returned to baseline by day 180 in all three subgroups. The average frequency of the H1N1-specific BMem at day 28 for the HIV /LAIV, HIV-/TIV and HIV+/TIV groups was 2.14%, 1.26% and 1.67%, respectively, and the average fold change was 14.39, 3.81 and 3.93, respectively. The differences of BMem between HIV-/LAIV and the two TIV subgroups were significant. For the IFNgamma response, the overall spot counts ranged widely between 0 and 958/106 PBMCs. The group average spot counts to H1N1 vaccine was 89, 102, and 30 at day 28 for HIV-/LAIV, HIV-/TIV and HIV+/TIV subgroups, respectively. The average increase of IFNgamma response at day 28 vs day 0 in all three subgroups did not reach 2-fold. CONCLUSION: Participants with a prior LAIV seasonal vaccine, as compared to a TIV seasonal vaccine, responded significantly better to the monovalent H1N1 vaccine. Excluding LAIV participants, no difference was seen between the HIV+ and HIV- subject groups in terms of BMem. The BMem response declined at 6months. PMID- 28987440 TI - Salmonella Enteritidis with double deletion in phoP fliC and a competitive exclusion culture elicit substantial additive protective effects against Salmonella exposure in newly hatched chicks. AB - A live Salmonella Enteritidis vaccine (SE147N DeltaphoP fliC), able to express both a homologous intestinal colonisation-inhibition effect and a systemic invasion-inhibition effect, was tested for its potential to generate a postulated additive protective effect in case of combined application with a competitive exclusion (CE) culture against Salmonella exposure in very young chicks. Both, SE147N DeltaphoP fliC and the CE culture alone were highly protective against systemic and intestinal colonisation of the challenge strain in case of moderate Salmonella exposure, consequently, additive protective effects in combined use could not be detected. However, in case of high Salmonella Enteritidis challenge with 106 cfu/bird at day 3 of life the combination of the DeltaphoP fliC vaccine and the CE culture resulted in a protective effect much more pronounced than either of the single preparations and most substantial compared to untreated control birds. The term additive protective effects reflects the recognition that exclusion effects by gut flora cultures and inhibition effects by Salmonella vaccines are caused by different mechanisms. PMID- 28987441 TI - Elaboration of tetravalent antibody responses against dengue viruses using a subunit vaccine comprised of a single consensus dengue envelope sequence. AB - Dengue viruses (DENVs) are re-emerging pathogens transmitted by mosquitoes mainly in tropical and subtropical regions. Each year, they are estimated to infect 390 million people globally. The major challenge confronting dengue vaccine development is the need to induce balanced, long lasting tetravalent immune responses against four co-circulating virus serotypes (DENV-I, -II, -III, -IV), because primary infection by any one of which may predispose infected individuals to more severe diseases during a heterotypic secondary infection. Another difficulty is to select representative strains in vaccine design to provide cross protection against most circulating virus strains. In this study, aimed at developing a tetravalent subunit vaccine with a representative single protein, we designed two vaccines (named cE80(D4) and cE80(max)) based on the consensus sequences of the ectodomain of envelope protein of 3127 DENV strains, and then expressed them in the baculovirus expression system. Both vaccines were capable of eliciting specific antibodies against all four DENV serotypes, and the predominant IgG subtype elicited by the two vaccines was IgG1. Moreover, these vaccines activated both type I and type II antigen-specific helper T cells that secreted IFN-gamma and IL-4, respectively. This proof-of-concept study has set foundation for further optimization of a single protein-based tetravalent DENV vaccine. PMID- 28987442 TI - Haemophilus influenzae type b carriage and burden of its related diseases in Chinese children: Systematic review and meta-analysis. AB - BACKGROUND: Haemophilus influenzae type b (Hib) is an important cause of invasive bacterial disease in children worldwide. The limited awareness of disease burden is a major barrier to the introduction of Hib vaccine into China's National Immunization Program. Therefore, we conducted a systematic review and meta analysis to estimate carriage of Hib and burden of its related diseases in Chinese children. METHODS: We systematically searched Pubmed, Web of Science, Ovid, Chinese National Knowledge Infrastructure (CNKI), and Wanfang databases for studies published up to December 31, 2016, reporting Hib carriage and burden of Hib diseases among children in Mainland China. Pooled estimates were obtained using random-effects models. RESULTS: We included 27 studies with 15783 children across 14 provinces. The pooled carriage of Hib was 5.87% (95% CI 3.42-8.33) for healthy children. The pooled proportion of disease due to Hib were 4.06% (95% CI 3.29-4.83) for acute lower respiratory tract infection (ALRI) and 27.32% (95% CI 0.41-54.24) for bacterial meningitis. The proportion of ALRI caused by Hib was higher in northern China than that in the south. Significant heterogeneity was noted across and within regions (P<0.001). After the induction of Hib vaccine, meta-regression showed that carriage of Hib changed little (P=0.725), but the proportion of ALRI caused by Hib in children decreased (P<0.001). CONCLUSIONS: Hib carriage persists at low levels among children in China. The proportion of ALRI due to Hib infection decreased with year. Incorporation of Hib vaccine into the National Immunization Program could reduce the burden of Hib disease in China. PMID- 28987443 TI - Vaccine hesitancy communication: What counts as evidence. AB - The evidence base for vaccine hesitancy communication is generally confined to research focused on the content of the message rather than the process of communication. This has important consequences, because shifting focus to encompass the process of communicating, and not just on the content of content message being conveyed; opens the possibility of greater insight and understanding regarding the conversation health care workers have with those who are vaccine hesitant, creating increased chances of acceptance. PMID- 28987444 TI - Vaccines against Shigella and enterotoxigenic Escherichia coli: A summary of the 2016 VASE Conference. AB - PATH hosted the inaugural Vaccines Against Shigella and Enterotoxigenic Escherichia coli (VASE) Conference in Washington, DC in June 2016, bringing together experts from around the world for a highly collaborative forum to discuss progress in the development of new enteric vaccines. Diarrheal disease and long-term sequelae caused by infections with the bacterial pathogens Shigella and enterotoxigenic E. coli (ETEC) pose a significant public health burden in low income communities. There are currently no licensed vaccines against these pathogens, and the global health community has recently prioritized their development. The 2016 VASE Conference aimed to accelerate communication and progress among those working in the enteric vaccine field to make Shigella and ETEC vaccines a reality as quickly as possible. Research presented in oral and poster presentations at the VASE Conference covered a range of topics, including: the global burden of disease and public health case for Shigella and ETEC vaccines; current vaccine candidates in development; immunology and host responses to the pathogens; and the rationale for and status of combined Shigella ETEC vaccine candidates. This article reviews key points and highlighted research presented in each of the plenary conference sessions and poster presentations at the 2016 conference. Planning for the 2018 VASE Conference is underway and will likely provide an important platform for sharing the latest updates on Shigella and ETEC vaccine research efforts and maintaining the momentum for accelerating this work. It is also expected that the VASE Conference will continue to provide a unique opportunity for those in the enteric vaccine field to share ideas, make connections, and create workable plans to make Shigella and ETEC vaccines a reality. (Updates available at: www.vaseconference.org.). PMID- 28987445 TI - Immunogenicity and safety of an inactivated quadrivalent influenza vaccine co administered with a 23-valent pneumococcal polysaccharide vaccine versus separate administration, in adults >=50years of age: Results from a phase III, randomized, non-inferiority trial. AB - INTRODUCTION: We compared co-administration versus separate administration of an inactivated quadrivalent influenza vaccine (IIV4) with a 23-valent pneumococcal polysaccharide vaccine (PPV23) in adults at high risk of complications of influenza and pneumococcal infection. METHODS: This phase III, placebo controlled, observer-blind trial (NCT02218697) was conducted in France and Belgium during the 2014-2015 influenza season. Adults>=50years of age meeting their country's vaccination recommendations were randomized 1:1 to co administration or separate administration. Immunogenicity was assessed by hemagglutination inhibition (HI) titers for IIV4 and 22F-inhibition ELISA for PPV23. Co-primary objectives were to demonstrate non-inferiority of co administration versus separate administration in terms of geometric mean titer (GMT) ratio for each influenza strain in the IIV4 and geometric mean concentration (GMC) ratio for six pneumococcal serotypes (1, 3, 4, 7F, 14, 19A) in the PPV23 in the per-protocol cohort (N=334). RESULTS: The study met its co primary objectives, with the upper limit of the 95% confidence interval of the GMT and GMC ratios (separate administration over co-administration) being <=2.0 for all four antigens of the IIV4 and the six pre-selected serotypes of the PPV23, respectively. Immunogenicity of the IIV4 and PPV23 was similar regardless of administration schedule. In a post hoc analysis pooling participants >=60years of age from the co-administration and separate administration groups, IIV4 immunogenicity was similar in higher risk adults with comorbidities (diabetes; respiratory, heart, kidney, liver, or neurological diseases; morbid obesity) versus those without. Both vaccines had an acceptable safety and reactogenicity profile; pain was the most common symptom, occurring more often with co administration than separate administration. CONCLUSION: The IIV4 and PPV23 can be co-administered without reducing antibody responses reflecting protection against influenza or pneumococcal disease. Co-administration of PPV23 at the annual influenza vaccination visit may improve uptake. Comorbidities had no impact on IIV4 immunogenicity, supporting its value in older adults with chronic medical conditions. Clinical Trial Registry Number: NCT02218697. PMID- 28987446 TI - Role of laser peripheral iridotomy in pigmentary glaucoma and pigment dispersion syndrome: A review of the literature. AB - PURPOSE: Pigment dispersion syndrome (PDS) is characterized by a structural abnormality of the posterior surface of the iris causing contact with the zonular fibers. It can lead to an open-angle glaucoma secondary to pigment dispersion into the trabecular meshwork. Laser peripheral iridotomy (PI) has been proposed as a treatment for pigmentary glaucoma (PG) and pigment dispersion syndrome (PDS) by reducing the dispersion of pigment. The goal of this review was to assess the effects of PI for PDS and PG. METHODS: We included six randomized controlled trials and two cohort studies (286 eyes of 218 participants). Four trials included participants with PG, and 4 trials enrolled participants with PDS with or without elevated intraocular pressure (IOP). RESULTS: Among patients with PG, at an average of 9 months of follow-up, the mean difference in IOP between groups was 2.69mm Hg less in the PI group (95% CI: -6.05 to 0.67; 14 eyes). In patients with PDS, the average IOP was statistically lower after PI as compared to baseline (Student test t=11.49, P<0.01, 38 eyes). With regard to visual field progression in participants with PG, after an average follow-up of 28 months, the risk of progression was not influenced by PI (RR 1.00 95% CI: 0.16 to 6.25; 32 eyes). No trials that enrolled patients with PDS showed a diminution of the risk of glaucoma conversion at mid- and long-terms. CONCLUSION: PI decreases the biomechanical factor causing contact between the iris and zonular fibers and may lower IOP over the long-term. Nevertheless, the effects of PI on visual field changes or progression have not been established in PG and PDS. There is no scientific evidence as of yet to advocate PI as a treatment for PDS or PG. PMID- 28987447 TI - [Total traumatic dislocation of the globe with transection of the optic nerve]. PMID- 28987448 TI - Fungal keratitis. AB - Fungal keratitis, or keratomycoses, are corneal infections which must be considered in cases of corneal trauma, prior corneal surgery, chronic ocular surface disease, topical corticosteroids or contact lens wear. Filamentous fungi or yeasts may be involved. Presenting clinical features such as corneal infiltrates with feathery edges and/or raised surface, intact epithelium with deep stromal involvement, satellite lesions, endothelial plaques, lack of improvement with antibiotics and worsening with steroids are suggestive of fungal keratitis. Corneal scraping for laboratory examination is mandatory. Medical management with antifungal eye drops and systemic agents should be started as soon as possible. Surgical interventions are required in a significant number of cases to control the infection. The prognosis of fungal keratitis is worse than that of bacterial keratitis. PMID- 28987449 TI - Management of Irvine-Gass syndrome. PMID- 28987450 TI - Differing responses of the estuarine bivalve Limecola balthica to lowered water pH caused by potential CO2 leaks from a sub-seabed storage site in the Baltic Sea: An experimental study. AB - Sub-Seabed CCS is regarded as a key technology for the reduction of CO2 emissions, but little is known about the mechanisms through which leakages from storage sites impact benthic species. In this study, the biological responses of the infaunal bivalve Limecola balthica to CO2-induced seawater acidification (pH7.7, 7.0, and 6.3) were quantified in 56-day mesocosm experiments. Increased water acidity caused changes in behavioral and physiological traits, but even the most acidic conditions did not prove to be fatal. In response to hypercapnia, the bivalves approached the sediment surface and increased respiration rates. Lower seawater pH reduced shell weight and growth, while it simultaneously increased soft tissue weight; this places L. balthica in a somewhat unique position among marine invertebrates. PMID- 28987451 TI - Smoking prevention in children and adolescents: A systematic review of individualized interventions. AB - OBJECTIVE: This study systematically reviewed the literature to determine what type of cognitive-behavioral based interventions administered outside of formal school settings effectively prevent smoking initiation among children and adolescents. METHODS: Applying the PRISMA guidelines we searched MEDLINE, PsycINFO, CINHAL, Pub Med, SCOPUS, and Sport Discus. Article review, data extraction, and assessment of risk of bias were conducted by two independent reviewers. RESULTS: We included 16 studies administered in various settings: seven in health care; four informally during and outside of school hours; three in the home; and two in extra-curricular settings. Positive preventive effects in smoking behavior ranging from 3-months to 4-years were observed in eight studies. Social environmental influences (e.g., parental smoking, friends) are salient contributing factors. CONCLUSIONS: Effective approaches involved interventions conducted in health care settings as well as those employing interpersonal communication and support strategies (e.g., via peer leaders, parent support, physicians). PRACTICE IMPLICATIONS: Primary health care settings may be optimal for implementing cigarette smoking prevention interventions for children and adolescents. Providing tailored education and facilitating interpersonal discussions between health care providers and families about the risks of smoking/strategies to avoid uptake, as well as capitalizing on technology-based modalities may reduce rates among children and adolescents. PMID- 28987453 TI - Hyalugel-integrated liposomes as a novel ocular nanosized delivery system of fluconazole with promising prolonged effect. AB - Fungal infections need long-term therapy with the proper antifungal agent. Despite effectiveness, Fluconazole (FLZ) ocular delivery is constrained by limited penetration, short residence time, in addition to the common barriers of the eye. Hyalugel-integrated liposomes were designed as novel ocular delivery systems integrating hyaluronic acid (HA) inside and surrounding vesicles by a simple preparation technique. The impact of combining HA hydrogel and liposomes was investigated in a series of different formulations. Full in-vitro optimization was performed regarding; HA and FLZ concentration, entrapment efficiency, particle size and stability to select the formula with the best characteristics. Structure elucidation of gel integration was done using polarizing and transmission electron microscopes before and after Triton-X100 addition. Corneal deposition and permeation were examined ex-vivo and in-vivo on male albino rabbits. Selected formulation (HYS7) showed gel-integrated structure, nanosize (218.50+/-4.50nm) and % EE 42.81%+/-1.66. Ex-vivo cumulative corneal permeation of FLZ after 6h from HYS7, was 2.99 and 4.18 folds higher than conventional liposomes and FLZ suspension, respectively. In-vivo corneal permeation of HYS7 showed unprecedented sustained effect of FLZ reaching 24h. In conclusion, novel hyalugel-integrated liposomes significantly enhanced corneal permeability compared to conventional liposomes and FLZ suspension. They would be promising alternates for eye drops; decreasing frequency of administration and increasing patients' compliance. PMID- 28987452 TI - Lancet Commission: Stem cells and regenerative medicine. PMID- 28987454 TI - In situ hydrogels enhancing postoperative functional recovery by reducing iron overload after intracerebral haemorrhage. AB - The role of surgery for most patients with spontaneous intracerebral haemorrhage (ICH) remains controversial due to the continuous occurrence of postoperative iron overload induced by low clot clearance rate. In this study, human hair keratose hydrogel (KG) loading with minocycline hydrochloride (MH) were prepared to reduce iron overload for the improvement of the postoperative functional recovery after ICH aspiration surgery. Hemoglobin-induced iron accumulation in rat primary neuronal culture was delayed by the adsorptive capacity of blank KG, while MH-loaded KG displayed a stronger and more thorough cytoprotective effect than blank KG due to the combined effect of absorptive action to iron and sustained release of the iron chelator. Moreover, high iron-chelating efficiency in the hematoma region supplied by MH-loaded KG significantly reduced dose strength of iron chelator. In situ injection of KG with different MH loadings (2, 20, and 200MUg) into the hematoma region after aspiration surgery showed a stronger effect on the reduction of ICH-induced iron accumulation, edema, and neurological deficits in rats compared to the postoperative intraperitoneal administration of MH (approximately 15mg). These results suggested that the in situ KG not only could effectively reduce the ICH postoperative iron overload and improve the postoperative functional recovery via the iron adsorption and sustained release of MH, but also has great potential to reduce the systemic adverse effects by decreasing the dose strength of iron chelator. PMID- 28987456 TI - Introduction of freedom of choice for hospital outpatient care in Portugal: Implications and results of the 2016 reform. AB - In Portugal, the National Health Service (NHS) assures universal access to medical treatment and care that is free at the point of delivery - except for relatively small user charges. Freedom of choice is limited and competition between the public and the private sectors is almost non-existent. In May 2016, the Ministry of Health introduced a new law that facilitates the referral of NHS users from primary healthcare units to outpatient consultations in NHS hospitals outside of the referral area. However, for inpatient care, patients are still bound to receive treatment within their referral area, which is determined by place of residence. The aim of the reform was to provide a timelier response to citizens' health needs and to increase efficiency. According to preliminary data from June 2016 to May 2017, 10.6% of all outpatient referrals from NHS primary health care units were made to an NHS hospital out of the referral area, with the highest proportion in the Lisbon (15.8%) region. In general, median waiting time for first outpatient consultation increased after the introduction of choice in the five specialties with the highest proportions of out-of-area referrals - but it reduced in two departments with the longest waiting times prior to the reform. The reform constitutes a major change to the relationship between NHS hospitals, with foreseeable consequences in hospital funding and the patients' perception of hospital quality. PMID- 28987455 TI - In vitro characterization and mouthfeel study of functionalized calcium carbonate in orally disintegrating tablets. AB - Orally disintegrating tablets (ODT) are comfortable and safe drug delivery methods beneficial for all age groups of patients. ODTs are characterized by fast disintegration, high physical stability, taste masking and acceptable mouthfeel. In this work, the applicability of Functionalized Calcium Carbonate (FCC) to formulate ODTs with enhanced mouthfeel was elaborated and tested for acceptability on twenty healthy volunteers, using a 10-step visual analog scale Mechanical characteristics of the ODTs were examined using Heckel analysis, modified Heckel analysis and Leuenberger equation. Disintegration time was measured with the tensiometer method and analyzed for disintegration kinetics with a system of ODE. As a result, it was shown that the tablet was well accepted in healthy volunteers, disintegrated fast in vivo and correlates well with the mathematical model. Additionally, the compactibility and the physical stability were preserved yielding high porosity to absorb liquid necessary for disintegration. In vitro disintegration time was successfully linked to in vivo disintegration time. These findings lead to the conclusion that FCC is applicable to use in ODT dosage forms and mouthfeel was successfully enhanced to a pleasant result without losing the unique characteristics of FCC. PMID- 28987457 TI - Migration intentions among Portuguese junior doctors: Results from a survey. AB - Migration of health personnel during periods of economic crisis represents a challenge for policymakers in origin and destination countries. Portugal is going through a period of economic hardship and much has been speculated about an increase in junior doctors' migration during this period. Using a questionnaire administered to a sample of Portuguese junior doctors who were still in the general residency (1st-year after medical school), we aim at determining the prevalence of migration intentions among Portuguese junior doctors and to identify the most important drivers of career choice for those who are considering emigrating in the near future. In our sample, 55% of Portuguese junior doctors are considering working abroad in the coming 10 years. Several variables were associated with an intention to work abroad: female sex (odds ratio [OR] 0.559; 95% confidence interval [CI] 0.488-0.640), the National Medical Exam score (OR 0.978; 95% CI 0.961-0.996;), having studied abroad (OR 1.756; 95% CI 1.086-2.867) and considering income and research opportunities as key factors for future specialty choice (OR 1.356; 95% CI 1.132-1.626; OR 2.626; 95% CI 1.228 4.172). Our study warns of the shortages the country may face due to doctors' migration and the main factors behind migration intentions in Portugal. Developing physician retention strategies is a priority to appropriately address these factors. PMID- 28987458 TI - Presence of cardiomyocytes exhibiting Purkinje-type morphology and prominent connexin45 immunoreactivity in the myocardial sleeves of cardiac veins. AB - BACKGROUND: Pulmonary vein (PV) myocardium is a known source of atrial fibrillation. A debated question is whether myocardial extensions into caval veins and coronary sinus (CS) have similar properties. No studies have documented specific pacemaker and/or conducting properties of human extracardiac myocardium. OBJECTIVE: The purpose of this study was to characterize the histology and immunohistochemical features of myocardial sleeves in the wall of cardiac veins. METHODS: Sections of 32 human hearts were investigated. Specimens of PVs, superior caval vein (SVC), CS, sinoatrial and atrioventricular nodes, and left ventricle were stained with Best's Carmine for selective staining of intracellular glycogen. Anti-connexin45 (Cx45)- and Cx43-specific antibodies were used to determine the conduction properties of extracardiac myocardium. RESULTS: Myocardial sleeve was found in the wall of PVs of 15 of 16 hearts, 21 of 22 SVCs, and 8 of 8 CSs. Bundles of glycogen-positive cardiomyocytes exhibiting pale cytoplasm and peripheral myofibrils were observed in the venous sleeves. Strong Cx45 and weak Cx43 labeling was detected in the extracardiac myocardium. Similar staining pattern was observed for the pacemaker and conduction system, whereas ventricular myocardium exhibited prominent Cx43 and no Cx45 immunoreactivity. CONCLUSION: Myocardial fibers of PVs, SVC, and CS exhibit morphology similar to that of Purkinje fibers and are enriched in glycogen. We provide data for the first time on prominent positive staining for Cx45 in the extracardiac myocardium, indicating its potential pacemaker and/or conducting nature. PMID- 28987459 TI - Long-term morbidity and mortality after implantable cardioverter-defibrillator implantation with procedural complication: A report from the National Cardiovascular Data Registry. AB - BACKGROUND: Long-term outcomes and predictors of mortality after implantable cardioverter-defibrillator (ICD) implantation related complication are unclear. OBJECTIVE: The purpose of this study was to determine the risk of mortality and hospitalization after complication during ICD implantation and identify predictors of adverse outcomes. METHODS: We performed a retrospective registry study of Medicare beneficiaries who were first-time ICD recipients enrolled in the National Cardiovascular Data Registry ICD Registry between January 2006 and March 2010. Mortality and hospitalization rates were examined using Kaplan-Meier survival analysis and multivariable Cox proportional hazards regression analysis. Covariates associated with mortality 3 years after ICD implantation complication were investigated. RESULTS: The study cohort comprised 136,143 Medicare beneficiaries. Complications during the index hospitalization occurred in 7046 patients (5.18%), and complications within 90 days of device implantation occurred in 10,005 patients (7.34%). In adjusted analyses, complications within 90 days of implantation were associated with an increased risk of all-cause mortality at 1 year (hazard ratio [HR] 1.13; 95% confidence interval [CI] 1.05 1.20; P = .006) and 3 years (HR 1.09; 95% CI 1.05-1.13; P <.0001). These results were consistent for a combined endpoint of all-cause mortality or hospitalization. Patient, device, and hospital characteristics associated with 3 year mortality were similar between those with and those without complications. CONCLUSION: Among Medicare beneficiaries, the occurrence of complications within 90 days of ICD implantation was associated with increased risk of all-cause mortality and all-cause mortality or hospitalization at 1 and 3 years. Patient, procedure, and hospital characteristics associated with mortality at 3 years after implantation were similar regardless of whether acute procedural complication occurred. PMID- 28987460 TI - Erratum to "The breast lesion excision system (BLES) under stereotactic guidance cannot be used as a therapeutic tool in the excision of small areas of microcalcifications in the breast" [EURR 93C (2017) 252-257]. PMID- 28987461 TI - Compensatory mechanisms in Parkinson's disease: Circuits adaptations and role in disease modification. AB - The motor features of Parkinson's disease (PD) are well known to manifest only when striatal dopaminergic deficit reaches 60-70%. Thus, PD has a long pre symptomatic and pre-motor evolution during which compensatory mechanisms take place to delay the clinical onset of disabling manifestations. Classic compensatory mechanisms have been attributed to changes and adjustments in the nigro-striatal system, such as increased neuronal activity in the substantia nigra pars compacta and enhanced dopamine synthesis and release in the striatum. However, it is not so clear currently that such changes occur early enough to account for the pre-symptomatic period. Other possible mechanisms relate to changes in basal ganglia and motor cortical circuits including the cerebellum. However, data from early PD patients are difficult to obtain as most studies have been carried out once the diagnosis and treatments have been established. Likewise, putative compensatory mechanisms taking place throughout disease evolution are nearly impossible to distinguish by themselves. Here, we review the evidence for the role of the best known and other possible compensatory mechanisms in PD. We also discuss the possibility that, although beneficial in practical terms, compensation could also play a deleterious role in disease progression. PMID- 28987462 TI - The developing utility of zebrafish models of neurological and neuropsychiatric disorders: A critical review. AB - Zebrafish (Danio rerio) have become a powerful tool in neuroscience research due to their genetic tractability, molecular/physiological conservation, small body size, ease of experimental manipulations in vivo, and rich behavioral repertoire. Zebrafish models and tests are particularly useful in genetics research, neurophenotyping, CNS drug screening, as well as in modeling complex neurological and psychiatric disorders. Here, we discuss selected examples of successful application of zebrafish models to mimicking various aspects of brain pathology, and emphasize their developing utility for studying the underlying molecular and genetic mechanisms. We also summarize recent advances in zebrafish-based CNS disease modeling, and outline new research strategies that may significantly improve translational neuroscience and experimental neurology research, and drug discovery. PMID- 28987463 TI - Therapeutic approaches to target alpha-synuclein pathology. AB - Starting two decades ago with the discoveries of genetic links between alpha synuclein and Parkinson's disease risk and the identification of aggregated alpha synuclein as the main protein constituent of Lewy pathology, alpha-synuclein has emerged as the major therapeutic target in Parkinson's disease and related synucleinopathies. Following the suggestion that alpha-synuclein pathology gradually spreads through the nervous system following a stereotypic pattern and the discovery that aggregated forms of alpha-synuclein can propagate pathology from one cell to another, and thereby probably aggravate existing deficits as well as generate additional symptoms, the idea that alpha-synuclein is a viable therapeutic target gained further support. In this review we describe current challenges and possibilities with alpha-synuclein as a therapeutic target. We briefly highlight gaps in the knowledge of the role of alpha-synuclein in disease, and propose that a deeper understanding of the pathobiology of alpha synuclein can lead to improved therapeutic strategies. We describe several treatment approaches that are currently being tested in advanced animal experiments or already are in clinical trials. We have divided them into approaches that reduce alpha-synuclein production; inhibit alpha-synuclein aggregation inside cells; promote its degradation either inside or outside cells; and reduce its uptake by neighbouring cells following release from already affected neurons. Finally, we briefly discuss challenges related to the clinical testing of alpha-synuclein therapies, for example difficulties in monitoring target engagement and the need for relatively large trials of long duration. We conclude that alpha-synuclein remains one of the most compelling therapeutic targets for Parkinson's disease, and related synucleinopathies, and that the multitude of approaches being tested provides hope for the future. PMID- 28987464 TI - Reentrainment of the circadian pacemaker during jet lag: East-west asymmetry and the effects of north-south travel. AB - The normal alignment of circadian rhythms with the 24-h light-dark cycle is disrupted after rapid travel between home and destination time zones, leading to sleep problems, indigestion, and other symptoms collectively known as jet lag. Using mathematical and computational analysis, we study the process of reentrainment to the light-dark cycle of the destination time zone in a model of the human circadian pacemaker. We calculate the reentrainment time for travel between any two points on the globe at any time of the day and year. We construct one-dimensional entrainment maps to explain several properties of jet lag, such as why most people experience worse jet lag after traveling east than west. We show that this east-west asymmetry depends on the endogenous period of the traveler's circadian clock as well as daylength. Thus the critical factor is not simply whether the endogenous period is greater than or less than 24 h as is commonly assumed. We show that the unstable fixed point of an entrainment map determines whether a traveler reentrains through phase advances or phase delays, providing an understanding of the threshold that separates orthodromic and antidromic modes of reentrainment. Contrary to the conventional wisdom that jet lag only occurs after east-west travel across multiple time zones, we predict that the change in daylength encountered during north-south travel can cause jet lag even when no time zones are crossed. Our techniques could be used to provide advice to travelers on how to minimize jet lag on trips involving multiple destinations and a combination of transmeridian and translatitudinal travel. PMID- 28987465 TI - Implications of iterative communication for biological system performance. AB - The performance of integrated biological systems can often be described by the behavior of component subunits: the proportion of subunits performing an activity, and the rate of recruitment to the activity, can be relevant to system performance. We develop a model for activation of subunits (receivers) to a task when activation requires repeated signals (iterative communication). The model predicts how system performance will be affected by the parameters of iterative communication. Receiver activation is influenced by the frequency of stimulation, by forgetting about past interactions, and by the number of stimuli needed to activate the receivers. These parameters, along with the probability of activated receivers returning to a de-activated state, modulate the system-wide time course of activation and the steady-state proportion of activated receivers. Parameters can interact to affect system-wide activation, and multiple parameter combinations can yield similar patterns of activation. Group performance is less variable at higher stimulation frequencies and in systems with greater numbers of receivers. Biological constraints on iterative communication, such as time and energy costs, may limit the parameter values that are feasible for a given system. Iterative communication parameters may be subject to natural selection at the system (group) level because they affect system performance. PMID- 28987466 TI - How ecosystems recover from pulse perturbations: A theory of short- to long-term responses. AB - Quantifying stability properties of ecosystems is an important problem in ecology. A common approach is based on the recovery from pulse perturbations, and posits that the faster an ecosystem return to its pre-perturbation state, the more stable it is. Theoretical studies often collapse the recovery dynamics into a single quantity: the long-term rate of return, called asymptotic resilience. However, empirical studies typically measure the recovery dynamics at much shorter time scales. In this paper we explain why asymptotic resilience is rarely representative of the short-term recovery. First, we show that, in contrast to asymptotic resilience, short-term return rates depend on features of the perturbation, in particular on the way its intensity is distributed over species. We argue that empirically relevant predictions can be obtained by considering the median response over a set of perturbations, for which we provide explicit formulas. Next, we show that the recovery dynamics are controlled through time by different species: abundant species tend to govern the short-term recovery, while rare species often dominate the long-term recovery. This shift from abundant to rare species typically causes short-term return rates to be unrelated to asymptotic resilience. We illustrate that asymptotic resilience can be determined by rare species that have almost no effect on the observable part of the recovery dynamics. Finally, we discuss how these findings can help to better connect empirical observations and theoretical predictions. PMID- 28987467 TI - Which clinical parameters should be used to determine systemic inflammation in cardiac surgery? PMID- 28987468 TI - Letter to Editor-Reply-Alternative terminology for the confusing term "palliative nutrition". PMID- 28987469 TI - Prevalence of sarcopenia and its association with activities of daily living and dysphagia in convalescent rehabilitation ward inpatients. AB - BACKGROUND: The purpose of this study was to investigate the prevalence of sarcopenia following stroke, musculoskeletal disease, or hospital-associated deconditioning in convalescent rehabilitation ward inpatients. The association between the activities of daily living (ADLs), dysphagia, and sarcopenia was also assessed. METHODS: A cross-sectional study was performed in consecutive patients admitted to convalescent rehabilitation wards. Sarcopenia was defined as a loss of skeletal muscle mass and decreased muscle strength. The primary outcome was the Functional Independence Measure (FIM) score. Body mass index, Mini Nutritional Assessment-Short Form score, Food Intake Level Scale (FILS) score, Charlson Comorbidity Index, premorbid modified Rankin scale, time from onset, reason for admission, bioelectrical impedance analysis for skeletal muscle mass and fat mass, and handgrip strength were also assessed. Univariate and multivariate analyses were used to determine whether ADLs and dysphagia were associated with sarcopenia. RESULTS: The study included 637 patients (mean age: 74 years; 271 men and 366 women). Sarcopenia was diagnosed in 343 (53.0%) patients (141 men and 202 women). Sarcopenia was identified in 53.6% (125/233) of stroke patients (59.8%, 50.0%, and 34.6% of patients with brain infarctions, brain hemorrhages, and subarachnoid hemorrhages, respectively). Sarcopenia was found in 51.3% (154/300) of patients with musculoskeletal diseases (59.5%, 53.6%, and 36.5% of patients with hip fractures, vertebral compression fractures, and total knee arthroplasty, respectively). Of patients with hospital-associated deconditioning, 61.5% (64/104) had sarcopenia (95.1% and 39.7% of patients with pneumonia and other acute diseases, respectively). Multivariate analysis showed that FIM motor domain and FILS scores were independently associated with skeletal muscle mass loss and decreased muscle strength. CONCLUSIONS: The prevalence of sarcopenia in convalescent rehabilitation ward inpatients was 53.0%. ADLs and dysphagia were independently associated with sarcopenia in this study population. Sarcopenia with disabilities should be assessed for all patients in rehabilitation settings. PMID- 28987470 TI - Potential therapeutic impact of omega-3 long chain-polyunsaturated fatty acids on inflammation markers in Duchenne muscular dystrophy: A double-blind, controlled randomized trial. AB - BACKGROUND & AIMS: Duchenne Muscular Dystrophy (DMD) is the most frequent dystrophy in childhood generated by a deficiency in dystrophin. DMD is a neuromuscular disease and its clinical course comprises chronic inflammation and gradual muscle weakness. Supplementation of omega-3 long chain-Polyunsaturated Fatty Acids (omega-3 long chain-PUFA) reduces inflammatory markers in various disorders. The goal of this research was to analyze the influence of omega-3 long chain-PUFA intake on gene expression and blood inflammatory markers in boys with DMD. METHODS: In a placebo-controlled, double. Blind, randomized trial, boys with DMD (n = 36) consumed 2.9 g/day of omega-3 long chain-PUFA or sunflower oil as control, in capsules, for a period of 6 months. Blood was analyzed at baseline and at months 1, 2, 3, and 6 of supplementation for expression of inflammatory markers in leukocytes and serum. RESULTS: There was high adherence to capsule intake (control: 95.3% +/- 7.2%, and omega-3 long chain-PUFA: 97.4% +/- 3.7% at month 6). Enrichment of EicosaPentaenoic Acid (EPA) and DocosaHexaenoic Acid (DHA) in erythrocytes increased significantly in patients supplemented with omega 3 long chain-PUFA compared with the placebo group during the 6 months of supplementation. Messenger RNA (mRNA) of the Nuclear Factor kappa beta (NF kappaB) and its target genes InterLeukin 1 beta (IL-1beta) and IL-6 was downregulated significantly (p < 0.05) in leukocytes from DMD boys supplemented with omega-3 long chain-PUFA for 6 months, compared to the placebo group. Omega-3 long chain-PUFA intake decreased the serum IL-1beta (-59.5%; p = 0.011) and IL-6 (-54.8%; p = 0.041), and increased the serum IL-10 (99.9%, p < 0.005), in relation to those with placebo treatment. CONCLUSION: Supplementation with omega 3 long chain-PUFA 2.9 g/day is well-tolerated, has a beneficial reductive effect on proinflammatory markers, and increases an anti-inflammatory marker, indicating that omega-3 long chain-PUFA could have a potential therapeutic impact on chronic inflammation in DMD. This research is registered at clinicaltrials.gov (NCT018264229). PMID- 28987471 TI - Foreword. PMID- 28987473 TI - Diagnosis and management of biliary injuries. PMID- 28987474 TI - Expression of checkpoint molecules on myeloid-derived suppressor cells. AB - Myeloid-derived suppressor cells (MDSCs) are a heterogeneous cell population expanded in cancer, infection and autoimmunity capable of suppressing T-cell functions. Checkpoint inhibitors have emerged as a key therapeutic strategy in immune-oncology. While checkpoint molecules were initially associated with T cell functions, recent evidence suggests a broader expression and function in innate myeloid cells. Previous studies provided first evidence for a potential role for checkpoints on MDSCs, yet the human relevance remained poorly understood. Therefore, we investigated the expression and functional relevance of checkpoint molecules in human MDSC-T-cell interactions. Our studies demonstrate that programmed death-ligand 1 (PD-L1) is expressed on granulocytic MDSCs upon co culture with T cells. Transwell experiments showed that cell-to-cell contact was required for MDSC-T-cell interactions and antibody blocking studies showed that targeting PD-L1 partially impaired MDSC-mediated T-cell suppression. Collectively, these studies suggest a role for PD-L1 in human MDSC function and thereby expand the functionality of this checkpoint beyond T cells, which could pave the way for further understanding and therapeutic targeting of PD-1/PD-L1 in innate immune-mediated diseases. PMID- 28987475 TI - Current perspectives on the role of CD8+ T cells in systemic sclerosis. AB - Despite long-standing recognition of the importance of T cells in systemic sclerosis (SSc; scleroderma), the role of CD8+ T cells in disease pathogenesis has not been well studied. Our work has shown that over-production of the pro fibrotic cytokine IL-13 by peripheral blood effector/memory CD8+ T cells is critical for predisposing patients to more severe forms of cutaneous fibrosis. Moreover, IL-13-producing CD8+ T cells induce a pro-fibrotic phenotype in normal and SSc dermal fibroblasts, and exhibit a strong cytotoxic activity ex vivo. We also found that CD8+ T cells are predominantly abundant in the skin lesions of patients in the early stages of diffuse cutaneous (dc)SSc compare to late-stage disease patients. Isolation of CD8+ T cells from the lesional skin of early active dcSSc patients, established that they are skin-resident, express cytolytic molecules and co-express extremely high levels of IL-13 and IFNgamma. Other recent studies corroborate these findings and together strongly suggest that CD8+ T cells contribute to SSc pathogenesis through the production of high levels of cytokines with pro-inflammatory and pro-fibrotic function as well as by exhibiting a cytotoxic activity. PMID- 28987477 TI - Three-Hour Bundle Compliance and Outcomes in Patients With Undiagnosed Severe Sepsis. AB - BACKGROUND: The aim of this study was to compare completion of the Surviving Sepsis Campaign 3-hour treatment recommendations and patient-centered outcomes between patients with severe sepsis who received a sepsis-specific diagnosis code with those who did not. METHODS: This was a retrospective cohort analysis of adult patients admitted through an academic medical center ED who received an antibiotic and met criteria for severe sepsis. We measured and compared the Surviving Sepsis Campaign 3-hour treatment recommendations along with patient centered outcomes in patients who were diagnosed with severe sepsis and those who were not. RESULTS: A total of 5,631 patients were identified (60.6 +/- 17.2 years of age; 48.9% women). Less than half (32.8%) received an International Classification of Diseases, ninth revision, diagnosis code of 995.92. Completion of all four bundle components in < 3 hours was low for all patients (8.72%). Therapeutic components (a broad-spectrum antibiotic and IV fluids) were completed more often (31.3%). Those with a diagnosis code received all four bundle components (10.2% vs 7.9%; P < .005), as well as therapeutic components at a higher frequency (36.0% vs 29.0%; P < .001). Patients with a diagnosis code had higher mortality (6.3% vs 2.3%), more frequent ICU admissions (44.7% vs 22.5%), and longer hospitalizations (9.2 +/- 6.9 days vs 6.9 +/- 6.7 days) than did patients with severe sepsis with no diagnosis code (all P < .001). CONCLUSIONS: Severe sepsis continues to be an underdiagnosed and undertreated condition. Patients who were diagnosed had higher treatment rates yet experienced worse outcomes. Continued investigation is needed to identify factors contributing to diagnosis, treatment, and outcomes in patients with severe sepsis. PMID- 28987476 TI - The MAIT conundrum - how human MAIT cells distinguish bacterial colonization from infection in mucosal barrier tissues. AB - We review the recent human mucosal-associated invariant T (MAIT) cell literature to examine the signals that control MAIT cell activation. We discuss these signals in context of MAIT cell function in mucosal barrier tissues and address how MAIT cells avoid responding to commensal bacteria, while maintaining responsiveness to infections. PMID- 28987478 TI - Clinical Impact of Intrapulmonary Vascular Dilatation in Candidates for Liver Transplant. AB - BACKGROUND: Intrapulmonary vascular dilatations (IPVD) frequently are detected in patients with liver disease by the delayed appearance of microbubbles at contrast enhanced echocardiography. IPVD with an elevated alveolar-arterial (A-a) gradient define hepatopulmonary syndrome (HPS); however, the importance of IPVD in the absence of abnormal gas exchange is unknown. We aimed to determine the clinical impact of IPVD in patients with liver disease. METHODS: We performed a cross sectional study within the Pulmonary Vascular Complications of Liver Disease 2 Study, a multicenter, prospective cohort study of patients being evaluated for liver transplant. We excluded patients with obstructive or restrictive lung disease, HPS, or intracardiac shunting. We compared patients with and those without IPVD. RESULTS: Forty-six patients with IPVD and 81 patients without IPVD were included. Patients with IPVD were more likely to have autoimmune hepatitis and less likely to have cryptogenic cirrhosis and hepatocellular carcinoma. Patients with IPVD had higher Child-Pugh scores (6 [interquartile range (IQR), 5 7] vs 5 [IQR, 4-7]; P = .04), possibly higher Model for End-Stage Liver Disease scores (14.5 [IQR, 11.6-15.8] vs 12.2 [IQR, 9.4-15.5]; P = .06), higher PaO2 levels (97.9 [IQR, 92.0-103.0] vs 89.0 [IQR, 82.0-96.9] mm Hg; P < .001), and lower A-a gradients (9.9 [IQR, 6.2-13.5] vs 14.9 [IQR, 9.0-21.8] mm Hg; P < .001). Symptoms and quality of life were similar between the groups. CONCLUSIONS: Autoimmune hepatitis and increased liver disease severity were associated with the presence of IPVD, which was characterized by higher PaO2 levels. Future studies to better characterize IPVD pathogenesis and the relationship of IPVD to HPS are warranted. PMID- 28987479 TI - Nurses' Early Recognition of Neonatal Sepsis. AB - OBJECTIVE: To determine nurses' perceptions of the most common physiologic and behavioral indicators of neonatal sepsis. DESIGN: Descriptive correlational study. SETTING: A women's and children's hospital in an academic medical center in the southwestern United States. PARTICIPANTS: Nurses (N = 181) who cared for neonates in the mother-infant and NICU settings. METHODS: Participants completed an e-mail survey developed from the literature to ascertain their perceptions of which physiologic and behavioral indicators were most often associated with neonatal sepsis. Descriptive and inferential statistics were used to analyze the data. RESULTS: Participants identified six signs and symptoms as indicators most often associated with sepsis: two were physiologic and four were behavioral. Recognition of these indicators was not related to level of nursing education but was associated with working in the NICU. Seventy-three percent of participants reported that they suspected that newborns were septic before evaluation and diagnosis of septicemia. CONCLUSION: Nurses can identify the physiologic and behavioral indicators related to neonatal sepsis. Early recognition, expressed as their intuitive knowing, should be considered a valuable clinical tool. Understanding that different practice settings influence identification of signs and symptoms is important. Integration of this knowledge into formal care surveillance could potentially lower the threshold for early evaluation and treatment and thereby improve outcomes. PMID- 28987480 TI - Egg white-derived peptides prevent cardiovascular disorders induced by mercury in rats: Role of angiotensin-converting enzyme (ACE) and NADPH oxidase. AB - The study aimed to investigate the effects of egg white hydrolysate (EWH) on vascular disorders induced by mercury (Hg). For this, male Wistar rats were treated for 60days: Untreated (saline, i.m.); Mercury (HgCl2, i.m., 1st dose 4.6MUg/kg, subsequent doses 0.07MUg/kg/day); Hydrolysate (EWH, gavage, 1g/kg/day); Hydrolysate-Mercury. Systolic (SBP) and diastolic (DBP) blood pressure measurement and vascular reactivity experiments in aorta were performed. We analyzed endothelial dependent and independent vasodilator responses and vasoconstrictor response to phenylephrine (Phe) in absence and presence of endothelium, a NOS inhibitor, a NADPH oxidase inhibitor, the superoxide dismutase, a non-selective COX inhibitor, a selective COX-2 inhibitor, an AT-1 receptors blocker. In situ superoxide anion production, SOD-1, NOX-4, p22phox, COX-2 and AT-1 mRNA levels and NOX-1 protein expression were performed in aorta while the determination of angiotensin converting enzyme (ACE) activity was measured in plasma. As results, EWH prevented the increase in SBP and Phe responses and the endothelial dysfunction elicited by Hg, which was related to decreased ACE activity and NOX activation by EWH and, subsequently, alleviated ROS production and improved NO bioavailability in aorta. In conclusion, EWH could be considered as alternative or complementary treatment tools for Hg-induced cardiovascular damage. PMID- 28987481 TI - MRI for in vivo diagnosis of cerebral amyloid angiopathy: Tailoring artifacts to image hemorrhagic biomarkers. AB - Cerebral amyloid angiopathy (CAA) is a frequent age-related small vessel disease (SVD) with cardinal magnetic resonance imaging (MRI) signatures that are hemorrhagic in nature, and include the presence of strictly lobar (superficial) cerebral microbleeds and intracerebral hemorrhages as well as cortical superficial siderosis. When investigating a patient with suspected CAA in the context of intracranial hemorrhage (parenchymal or subarachnoid) or cognitive dysfunction, various MRI parameters influence the optimal detection and characterization (and prognostication) of this frequent SVD. The present report describes the influence of imaging techniques on the detection of the key hemorrhagic CAA imaging signatures in clinical practice, in research studies, and the imaging parameters that must be understood when encountering a CAA patient, as well as reviewing CAA literature. PMID- 28987482 TI - A single-domain rhodanese homologue MnRDH1 helps to maintain redox balance in Macrobrachium nipponense. AB - Rhodaneses are known to catalyze in vitro the transfer of a sulfane sulfur atom from thiosulfate to cyanide with concomitant formation of thiocyanate, however, their biological functions remain speculative despite the main role is considered as detoxifying cyanide especially in animal livers. In this study, we characterized a single-domain rhodanese homologue, MnRDH1, from Macrobrachium nipponense. We found MnRDH1 with the highest expression in hemocytes. Upon Aeromonas hydrophila challenge, expression of MnRDH1 was up-regulated in various tissues, including hepatopancreas, gill, intestine and hemocytes. RNAi knockdown of MnRDH1 led to rapid increases of malondialdehyde content, which reveals that MnRDH1 deficiency causes oxidative stress. The expression of MnRDH1 in hepatopancreas was significantly increased in response to the doxorubicin-induced oxidative stress, indicating the gene is oxidative stress inducible. We transformed E. coli with MnRDH1 and the mutant MnRDH1C75A, and found significant rhodanese activity of the recombinant protein of MnRDH1 in vitro, but detected no enzyme activity of the mutant MnRDH1C75A. When under the oxidative insult by H2O2, the MnRDH1 transformed E. coli had significantly enhanced survival rates compared to those bacteria transformed with MnRDH1C75A. In conclusion, our study demonstrates that rhodanese in M. nipponense confers oxidative stress tolerance, and thus renders an evidence for the notion that rhodanese family genes act a critical role in antioxidant defenses. PMID- 28987483 TI - Efficacy of adjuvant laser therapy in reducing postsurgical complications after the removal of impacted mandibular third molars: A systematic review update and meta-analysis. AB - BACKGROUND: The authors updated a previously published systematic review to assess the effects of low-level laser therapy (LLLT) on reducing complications after the removal of impacted mandibular third molars. TYPES OF STUDIES REVIEWED: The authors searched for randomized clinical trials in which the investigators evaluated the efficacy of LLLT compared with that of placebo or no treatment. Two reviewers independently screened studies, extracted data, and assessed risk of bias. The authors used random effects model meta-analysis and the Grading of Recommendations Assessment, Development and Evaluation approach to rate the certainty of evidence. RESULTS: The authors included 21 studies. There was low certainty evidence that LLLT results in less pain at 2 days after surgery (mean difference [MD], -1.42 on a 10 point scale; 95% confidence interval [CI], -2.18 to -0.67) and moderate certainty that it results in negligibly less pain at 7 days (MD, -0.59; 95% CI, -0.96 to -0.22); moderate-certainty evidence that LLLT has a negligible benefit on reducing trismus at 2 days (MD, -3.42 millimeters; 95% CI, -5.34 to -1.50) and at 7 days after surgery (MD, -2.30 mm; 95% CI, -3.96 to -0.64); lastly, there was moderate-certainty evidence that LLLT results in less postoperative swelling at 2 days (standardized MD, -0.82; 95% CI, -1.28 to 0.35) and low-certainty evidence that LLLT results in negligibly less postoperative swelling at 7 days after surgery (standardized MD, -0.17; 95% CI, 0.4 to 0.07). Low-quality evidence suggests that LLLT will not cause adverse effects. CONCLUSIONS AND PRACTICAL IMPLICATIONS: LLLT probably has negligible benefits but may not result in adverse events. Evidence does not support the use of LLLT in clinical practice to reduce complications after impacted mandibular third-molar surgical extractions. PMID- 28987484 TI - Limitations in systematic review comparing the outcomes of single implant mandibular overdentures with complete conventional dentures render it unuseful in making clinical decisions. PMID- 28987485 TI - Naproxen gel probably has no important benefit in minimizing pain after orthodontic separator placement. PMID- 28987486 TI - Insufficient evidence about the influence of tooth characteristics on pit-and fissure sealant performance. PMID- 28987488 TI - Post-retained single crowns placed in endodontically treated teeth with more than 50% of dental tissue remaining probably have a high survival after 7 years. PMID- 28987487 TI - Patients with periodontitis may be more likely to have halitosis, but the magnitude of this association and its importance to patients is uncertain. PMID- 28987489 TI - Insufficient evidence for the association between diabetes mellitus and healing of periapical lesions. PMID- 28987490 TI - Nail braces for severe paronychia induced by epidermal growth factor receptor inhibitors: An alternative to nail extraction. PMID- 28987491 TI - Treatment for facial alopecia areata: A systematic review with evidence-based analysis. PMID- 28987492 TI - Detection and characterization of IgG, IgE, and IgA autoantibodies in patients with bullous pemphigoid associated with dipeptidyl peptidase-4 inhibitors. PMID- 28987493 TI - Risk of infection in patients with atopic dermatitis treated with dupilumab: A meta-analysis of randomized controlled trials. AB - BACKGROUND: Atopic dermatitis (AD) is characterized by skin barrier defects, T helper type 2 cell activation, and increased risk for cutaneous and extracutaneous infections. In clinical trials, dupilumab appeared to decrease rates of skin infections in AD. OBJECTIVE: We aimed to determine the impact of dupilumab on rates of skin and other infections in patients with moderate-to severe AD. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials of dupilumab for AD. We searched the PubMed database for relevant studies. Risk ratios (RRs) and 95% confidence intervals (CIs) for skin infections, herpesvirus infections, and overall infections and infestations were calculated for dupilumab compared with for placebo by using binary random effects meta-analysis. For the analysis of eczema herpeticum, Peto odds ratios were calculated. RESULTS: Eight randomized controlled trials in 4 publications with 2706 participants were included, with follow-up time ranging from 4 to 52 weeks. Meta-analysis including all dosing schedules and follow-up times showed a RR of skin infection of 0.54 (95% CI, 0.42-0.70) and an odds ratio of eczema herpeticum of 0.34 (95% CI, 0.14-0.84) for dupilumab compared with placebo. No significant association was found for dupilumab with overall herpesvirus infections (RR, 1.16; 95% CI, 0.78-1.74) and overall infections (RR, 0.98; 95% CI, 0.83-1.16). LIMITATIONS: Our analysis is limited by the short follow-up time in most trials and the relatively low number of patients treated with dupilumab to date. CONCLUSIONS: Dupilumab is associated with a decreased incidence of skin infections and eczema herpeticum in adults with moderate-to-severe AD. The mechanism underlying this association is uncertain but is likely related to improvement in AD severity. Dupilumab, a monoclonal antibody targeting interleukin 4 and interleukin 13, appears to significantly decrease the risk for skin infections and eczema herpeticum in adults with moderate-to-severe AD. PMID- 28987494 TI - Randomized, placebo-controlled, double-blind study of oral tranexamic acid in the treatment of moderate-to-severe melasma. AB - BACKGROUND: Melasma is a common pigmentary disorder that is often difficult to treat. Tranexamic acid (TA) has emerged as a promising treatment for melasma; however, few controlled studies exist. OBJECTIVE: To determine the efficacy of oral TA in patients with moderate-to-severe melasma. METHODS: Patients with moderate-to-severe melasma were treated with 250 mg of TA or placebo capsules twice daily for 3 months and sunscreen followed by 3 months of treatment with sunscreen only. The primary outcome measure was the modified Melasma Area and Severity Index (mMASI) score. RESULTS: A total of 44 patients were enrolled and 39 completed the study. At 3 months, there was a 49% reduction in mMASI score in the TA group versus 18% in the control group. Patients with severe melasma improved more than those with moderate melasma. Three months after treatment was stopped, there was a 26% reduction in mMASI score in the TA group compared with the baseline visit versus a 19% reduction in the placebo arm. No serious adverse events were noted in either group. LIMITATIONS: Single-center study enrolling predominantly Hispanic women. CONCLUSIONS: Oral TA appears to be an effective treatment for moderate-to-severe melasma with minimal side effects. PMID- 28987495 TI - Late ophthalmological manifestations in patients with subarachnoid hemorrhage and coiling of cerebral aneurysm. AB - Late ocular manifestations of aneurysmal subarachnoid hemorrhage (SAH) have not been previously investigated except for one study which demonstrated that one half of patients subjected to aneurysm clipping suffer from symptoms of visual pathway impairment. We assessed ophthalmological status of patients after 1-4.5 years from SAH and aneurysm embolization to identify predictors of damage to the visual pathways. Complete ophthalmological examination, static perimetry, and visual evoked potentials (VEPs) were performed in 74 patients (26 men, 48 women, aged 19-76 years), who constituted a consecutive sample of 129 patients treated with aneurysm embolization in the years 2008-2010. The following independent variables: sex, age, time from SAH to embolization, size and site of aneurysm, score in Glasgow Coma Scale, Glasgow Outcome Scale, Hunt-Hess and Fisher scales were subject to univariate and multivariate statistical analyses to study their influence on the ocular outcome. 40 patients (54%) demonstrated visual field defects appearing as multiple peripheral foci and constricted field, affecting both eyes. Among these subjects, 12 patients had severe defects in the visual field, 20 had deterioration in VEPs, and 9 had decreased visual acuity. Older age and high score in Hunt-Hess and Fisher scales were identified as predictors for visual field defects and disturbances in VEPs. More than half of the survivors of SAH and aneurysm embolization suffer from a permanent defect in visual function. Damage of visual pathway correlates with severity of SAH and older age of patients. PMID- 28987496 TI - Low-symptomatic skeletal muscle disease in patients with a cardiac disease - Diagnostic approach in skeletal muscle laminopathies. AB - Mild skeletal muscle symptoms might be accompanied with severe cardiac disease, sometimes indicating a serious inherited disorder. Very often it is a cardiologist who refers a patient with cardiomyopathy and/or cardiac arrhythmia and discrete muscle disease for neurological consultation, which helps to establish a proper diagnosis. Here we present three families in which a diagnosis of skeletal muscle laminopathy was made after careful examination of the members, who presented with cardiac arrhythmia and/or heart failure and a mild skeletal muscle disease, which together with positive family history allowed to direct the molecular diagnostics and then provide appropriate treatment and counseling. PMID- 28987497 TI - Optimization of a new method for extraction of cyanidin chloride and pelargonidin chloride anthocyanins with magnetic solid phase extraction and determination in fruit samples by HPLC with central composite design. AB - Here, we are reporting a sensitive, simple and rapid method for the analysis of cyanidin chloride and pelargonidin chloride anthocyanins in cherry, sour cherry, pomegranate and barberry produced in Iran. The analytes were extracted with acetonitrile-hydrochloric acid (1% v/v) mixture under optimized pretreatment conditions. Clean-up of the extract from fruits was conducted by magnetic solid phase extraction using salicylic acid functionalized silica-coated magnetite nanoparticles (SCMNPs) as the adsorbent. The optimized conditions searched with central composite design. Working under optimum conditions specified as: SCMNPs modified with salicylic acid, sorbent contact time and sample 10min, mechanical stirring time 57.3min. HPLC with UV-detection was used for determination of the analytes. The limit of detection, LOD, obtained for the two anthocyanins were 0.02 and 0.03MUgg-1, respectively. The ranges of the spiked recoveries were 80.0 97.6 and 72.9-97.2%, with the relative standard deviations (RSD) of 2.1 and 2.5%, respectively. PMID- 28987498 TI - MOF-5(Zn)-Fe2O4 nanocomposite based magnetic solid-phase microextraction followed by HPLC-UV for efficient enrichment of colchicine in root of colchicium extracts and plasma samples. AB - In present work, facile method is developed for determination of colchicine in human plasma sample, autumn and spring root of colchicium extracts by ultrasound assisted dispersive magnetic solid phase microextraction followed by HPLC-UV method (UAD-MSPME-HPLC-UV). Magnetic (Fe2O4-nanoparticles) metal organic framework-5, (MOF-5(Zn)-Fe2O4NPs) was synthesized by dispersing MOF-5 and Fe(NO3)3.9H2O in ethylene glycol (as capping agent) and NaOH (pH adjustment agent) by hydrothermal method. The prepared sorbent was characterized via XRD and SEM analysis and applied as magnetic solid phase in UAD-MSPME-HPLC-UV method. In this method, colchicine molecules were sorbed on MOF-5(Zn)-Fe2O4NPs sorbent by various mechanisms like ion exchange, hydrogen bonding and electrostatic, ?-?, hard-hard and dipole-ion interaction followed by exposing sonication waves as incremental mass transfer agent and then the sorbent was separated from the sample matrix by an external magnetic fields. Subsequently, accumulated colchicine were eluted by small volume of desorption organic solvent. Influence of operational variables such as MOF-5(Zn)-Fe2O4NPs mass, volume of extracting solvent and sonication time on response property (recovery) were studied and optimized by central composite design (CCD) combined with desirability function (DF) approach. Under optimum condition, the method has wide linear calibration rang (0.5-1700ngmL-1) with reasonable detection limit (0.13ngmL-1) and R2=0.9971. Finally, the UAD-MSPME-HPLC-UV method was successfully applied for determination of colchicine autumn and spring root of colchicium extracts and plasma samples. PMID- 28987499 TI - Improving the Carprofen Solubility: Synthesis of the Zn2Al-LDH Hybrid Compound. AB - The development of efficient strategies for drug delivery is considerably desired. Indeed, often several issues such as the drug solubility, the control of the drug release rate, the targeted delivery of drugs, the drug bioavailability, and the minimization of secondary effects still present great obstacles. Different methodologies have been proposed, but the use of nano-hybrids compounds that combine organic and inorganic substances seems particularly promising. An interesting inorganic host is the layered double hydroxide (LDH) with a sheets structure and formula [M2+1-x M3+x (OH)2](An-)x/n yH2O (M2+ = Zn, Mg; M3+ = Al; An- = nitrates, carbonates, chlorides). The possibility to exchange these counterions with drug molecules makes these systems ideal candidates for the drug delivery. In this article, we synthesize by co-precipitation method the hybrid compound Carprofen-Zn2Al-LDH. Carprofen, a poorly soluble anti-inflammatory drug, could also benefit of the association with a natural antacid such as LDH, to reduce the gastric irritation after its administration. Through X-ray diffraction and Fourier-transformed infrared spectroscopy (FT-IR), we could verify the effective drug intercalation into LDH. The dissolution tests clearly demonstrate a significant improvement of the drug release rate when carprofen is in the form of hybrid compound. PMID- 28987501 TI - Composite Alginate-Hyaluronan Sponges for the Delivery of Tranexamic Acid in Postextractive Alveolar Wounds. AB - The management of wounds in patients on anticoagulant therapy who require oral surgical procedures is problematic and often results in a nonsatisfactory healing process. Here, we report a method to prepare an advanced dressing able to avoid uncontrolled bleeding by occluding the postextractive alveolar wounds, and simultaneously, capable of a fast release of tranexamic acid (TA). Composite alginate/hyaluronan (ALG/HA) sponge dressings loaded with TA were prepared by a straightforward internal gelation method followed by a freeze-drying step. Both blank and drug-loaded sponges were soft, flexible, and elegant in appearance and nonbrittle in nature. Scanning electron microscopy analysis confirmed the porous nature of these dressings. The integration of HA influenced the microstructure, reducing the porosity, modifying the water uptake kinetic, and increasing the resistance to compression. TA release from ALG/HA sponges showed a controlled release up to 3 h, and it was faster in the presence of HA. Finally, an in vitro clotting test performed on human whole blood confirmed that the TA-loaded sponges significantly reduce the blood clotting index by 30% compared with ALG/HA20 sponges. These results suggest that, if placed in a socket cavity, these dressings could give a relevant help to the blood hemostasis after dental extractions, especially in patients with coagulation disorders. PMID- 28987500 TI - Evaluating Suspension Formulations of Theophylline Cocrystals With Artificial Sweeteners. AB - Pharmaceutical cocrystals have garnered significant interest as potential solids to address issues associated with formulation development of drug substances. However, studies concerning the understanding of formulation behavior of cocrystals are still at the nascent stage. We present results of our attempts to evaluate suspension formulations of cocrystals of an antiasthmatic drug, theophylline, with 2 artificial sweeteners. Stability, solubility, drug release, and taste of the suspension formulations were evaluated. Suspension that contained cocrystal with acesulfame showed higher drug release rate, while a cocrystal with saccharin showed a significant reduction in drug release rate. The cocrystal with saccharin was found stable in suspension for over 9 weeks at accelerated test condition; in contrast, the cocrystal with acesulfame was found unstable. Taste analysis using an electronic taste-sensing system revealed improved sweetness of the suspension formulations with cocrystals. Theophylline has a narrow therapeutic index with a short half-life which necessitates frequent dosing. This adversely impacts patient compliance and enhances risk of gastrointestinal and cardiovascular adverse effects. The greater thermodynamic stability, sweetness, and sustained drug release of the suspension formulation of theophylline-saccharin could offer an alternative solution to the short half-life of theophylline and make it a promising formulation for treating asthmatic pediatric and geriatric patients. PMID- 28987502 TI - Optimal Histologic Cutpoints for Treatment Response in Patients With Eosinophilic Esophagitis: Analysis of Data From a Prospective Cohort Study. AB - BACKGROUND AND AIMS: No prospective studies substantiate 15 eos/hpf as an appropriate endpoint for treatment of eosinophilic esophagitis (EoE). We aimed to determine a histologic cutpoint that identifies successful treatment of EoE by assessing symptomatic and endoscopic improvement. METHODS: We performed a prospective cohort study of 62 consecutive adult patients undergoing outpatient esophagogastroduodenoscopy at the University of North Carolina from 2009 through 2014. At diagnosis of EoE and after 8 weeks of standard treatment, symptom and endoscopic responses were measured using a visual analogue scale and an endoscopic severity score (ESS), and eosinophil counts were assessed. Receiver operator curves and logistic regression models evaluated the histologic threshold that best predicted symptomatic and endoscopic response. For symptoms, analysis was limited to patients without baseline esophageal dilation. RESULTS: The mean eosinophil count at diagnosis was 124 eos/hpf, falling to 35 eos/hpf after treatment. The mean visual analogue scale decreased from 3.4 at baseline to 1.7 after treatment, and the mean ESS decreased from 3 to 1.6. Twenty-nine patients had symptom responses (47%) and 34 had endoscopic responses (55%). Post-treatment eosinophil count thresholds of 8, 15, and 5 eos/hpf best predicted symptom, endoscopic and combined responses, respectively. On logistic regression, decreasing eosinophil count was significantly associated with the probability of symptomatic (P = .01) and endoscopic response (P < .001). CONCLUSIONS: In a prospective study of patients with EoE, we found that a cutpoint of <15 eos/hpf identifies most patients with symptom and endoscopic improvements, providing support for the current diagnostic threshold. A lower threshold (<5 eos/hpf) identifies most patients with a combination of symptom and endoscopic responses; this cutpoint might be used in situations that require a stringent histologic threshold. PMID- 28987503 TI - A Comparison of Staging Systems for Hepatocellular Carcinoma in a Multicenter US Cohort. PMID- 28987504 TI - Is High-Resolution Manometry Always Needed for the Diagnosis of Achalasia? PMID- 28987505 TI - Another Reason to Avoid the Gluten-Free Fad? PMID- 28987506 TI - Colorectal Cancer Genetics Screening in the Community: Are We Ready? Can We Do It? PMID- 28987507 TI - Patients Are Willing to Repeat Colonoscopy at a Short Interval When Bowel Preparation Quality Is Suboptimal. PMID- 28987508 TI - Acylated and unacylated ghrelin confer neuroprotection to mesencephalic neurons. AB - The polypeptide ghrelin is an endogenous ligand at the growth hormone secretagogue receptor 1a. To ghrelin multiple functions have been ascribed including promotion of gastrointestinal motility. Postprandial ghrelin levels have been reported to be reduced in patients suffering from Parkinson disease (PD). Experimental studies revealed neuroprotective effects of ghrelin in different PD models. The purpose of the present study was (i) to further elucidate the mechanism underlying the neuroprotective action of ghrelin and (ii) to determine whether these effects occur with both the acylated and the unacylated form. The study was conducted in primary mesencephalic cultures treated with mitochondrial complex I and complex II inhibitors. We show that protective effects of ghrelin against complex I inhibition with MPP+ were independent of the acylation status of ghrelin, although acylated ghrelin appeared to be more potent. Protection by both forms was also observed when neurons were exposed to the complex II inhibitor 3-NP. Both forms led to higher oxygen consumption rates upon electron transport chain uncoupling, indicating that the two peptides may exert uncoupling effects themselves. We demonstrate that the rescue provided by ghrelin required calcium influx through L-type voltage-gated calcium channels. Whereas the protective effects of acylated ghrelin required receptor binding, effects of the unacylated form remained unaffected by treatment with a ghrelin receptor antagonist. Importantly, inhibition of ghrelin O-acyltransferase failed to reduce the activity of unacylated ghrelin. Overall, our data suggest that both acylated and unacylated ghrelin afford protection to dopamine neurons but through mechanisms that only partially overlap. PMID- 28987509 TI - White Matter Microstructural Properties are Related to Inter-Individual Differences in Cognitive Instability after Sleep Deprivation. AB - Several diseases are characterized by cognitive instability, which is amplified in the conditions of sleep deprivation (SD). Cognitive instability in SD can be examined by the number of lapses on the psychomotor vigilance test (PVT), which is considered to be a gold standard in the field. However, the number of PVT lapses widely range according to inter-individual differences, from apparent cognitive resistance to severe cognitive impairment. In this study, tract-based spatial statistical analyses with multiple diffusion tensor imaging-derived characteristics (i.e., fractional anisotropy (FA), mean diffusivity, radial diffusivity, and axial diffusivity) were employed to investigate the relationships between the number of PVT lapses and the diffusion characteristics. A hierarchical linear regression model was then used to assess the contributions of tract-specific FA values in predicting PVT lapses. Finally, dichotomized analysis was used to investigate white matter (WM) differences between resilient and vulnerable groups. Our results showed significant negative correlations between numbers of PVT lapses and FA in multiple WM tracts, with the FA variations in the superior longitudinal fasciculus and splenium of the corpus callosum accounting for nearly 37.5% of individual variability in PVT lapses. In addition, dichotomized analyses indicated that the resilient participants exhibited significantly higher FA values compared with the vulnerable participants. Together, these findings suggest that cognitive instability after SD was closely associated with individual differences in WM integrity. PMID- 28987510 TI - Aging-Related Oxidative Stress: Positive Effect of Memory Training. AB - The cognitive impairment characterizing the phenotype of older adults has been related to the efficiency of the antioxidant system. This study aimed at investigating the effect of memory training (MT) on memory, global cognitive functioning, and the oxidant and antioxidant capacity of plasma. We recruited 52 healthy subjects aged over 60. Twenty-nine subjects were submitted to 6-months of MT (Experimental Group, EG), and 23 were used as a Control Group (CG). Global cognitive functioning was assessed by the Mini-Mental State Examination (MMSE) and Short- and Long-Term Memory (STM and LTM, respectively) by the Rey Auditory Verbal Learning Test (RAVLT) at baseline (T0) and after 6-months (T1). Meanwhile, Reactive Oxygen Metabolites derivative compounds (d-ROMs), Biological Antioxidant Potential (BAP), and their ratio were evaluated on plasma. Results showed that the MMSE and RAVLT scores improved in EG at T1. At the same time, the d-ROMs levels significantly decreased, while the BAP and BAP/d-ROMs ratio showed an opposite trend. In both groups, the MMSE and LTM scores were negatively associated with d-ROMs levels, and positively correlated with BAP levels and the BAP/d-ROMs ratio. When we considered the Deltavalue (Deltavariable = variable post-MT minus variable pre-MT) in EG, the DeltaMMSE and DeltaLTM scores were negatively associated to Deltad-ROMs, and positively to DeltaBAP and DeltaBAP/dROM. In conclusion, our results suggest that MT improves memory and global cognitive functioning. These processes were significantly associated to increase in resistance against oxidative stress at the plasma level in healthy older adults. PMID- 28987511 TI - SOCS3 ablation in SF1 cells causes modest metabolic effects during pregnancy and lactation. AB - Previous studies have shown that leptin resistance is a key feature that leads to gestational metabolic adaptions. We hypothesized that leptin sensitivity in the ventromedial nucleus of the hypothalamus (VMH) plays a critical role regulating gestational metabolic changes. In the present study, we generated a mouse model carrying ablation of the suppressor of cytokine signaling 3 (SOCS3) in steroidogenic factor-1 (SF1) cells, which include the VMH, in order to investigate whether increased leptin sensitivity in this neuronal population prevents at least part of the metabolic changes typically observed during gestation and lactation. As predicted by the inhibitory effects of SOCS3 in leptin signaling, pregnant SF1 SOCS3 KO mice exhibited increased leptin sensitivity in the VMH, since an acute leptin injection induced a 95% increase in the STAT3 phosphorylation in this nucleus, compared to control animals (p = 0.02). Despite that, SF1 SOCS3 KO mice showed similar weight gain, food intake, hypothalamic neuropeptide expression and serum leptin levels during pregnancy compared to control littermates. Unexpectedly, SF1 SOCS3 KO mice exhibited glucose intolerance during pregnancy. SF1 SOCS3 KO mice also presented a lower body weight (-3%; p < 0.05) during mid and late lactation, although food intake, litter size and offspring growth were not affected. Our findings suggest that increased leptin sensitivity in the VMH causes modest metabolic effects and is not sufficient to prevent major metabolic adaptations of pregnancy and lactation. PMID- 28987512 TI - Genes Linking Mitochondrial Function, Cognitive Impairment and Depression are Associated with Endophenotypes Serving Precision Medicine. AB - Mitochondria densely populate cells in central nervous system providing essential energy for neurons and influencing synaptic plasticity. Harm to these organelles can impair cognitive performance through damaged neurotransmission and altered Ca2+ homeostasis. Impaired cognition could be one underlying factor which can characterize major depressive disorder, a huge burden for society marked by depressed mood and anhedonia. A growing body of evidence binds mitochondrial dysfunctions with the disease. Cognitive disturbances with different severity are also observable in several patients, suggesting that damage or inherited alterations of mitochondria may have an important role in depression. Since several different biological and environmental factors can lead to depression, mitochondrial changes may represent a significant subgroup of depressive patients although cognitive correlates can remain undiscovered without a specific focus. Hypothesis driven studies instead of GWAS can pinpoint targets relevant only in a subset of depressed population. This review highlights results mainly from candidate gene studies on nuclear DNA of mitochondrion-related proteins, including TOMM40, MTHFD1L, ATP6V1B2 and MAO genes, also implicated in Alzheimer's disease, and alterations in the mitochondrial genome to argue for endophenotypes where impaired mitochondrial function may be the leading cause for depressive symptomatology and parallel cognitive dysfunction. PMID- 28987513 TI - Novel strategy for improving the bioavailability of curcumin based on a new membrane transport mechanism that directly involves solid particles. AB - Amorphization has been widely recognized as a useful solubilization technique for poorly water-soluble drugs, such as curcumin. We have recently reported the novel finding that the membrane transport of curcumin was markedly enhanced when amorphous solid particles of curcumin came into direct contact with the lipid membrane surface, but this was not true for crystalline solid particles. The increase in the permeation of curcumin was found to be independent of the improvements in aqueous solubility brought about by amorphization. Thus, we have identified a novel membrane transport mechanism that directly involves solid particles. In addition, it might represent a novel strategy for improving the bioavailability of curcumin that does not focus on the aqueous solubility of the drug. In this study, the direct effects of the administration of amorphous nanoparticles of curcumin (ANC) on the in vivo intestinal absorption of curcumin were investigated. After the intraduodenal administration of a curcumin suspension, the area under the curve of the plasma concentration of curcumin increased in a manner that was dependent on the curcumin concentration of the suspension, while no significant absorption was observed from a saturated solution. This finding is consistent with the results from our in vitro transepithelial transport study. In the latter experiment, the bioavailability of curcumin was found to be 1-2%. The intrapulmonary insufflation of ANC powder resulted in a significant increase in the bioavailability of curcumin (it was two orders of magnitude higher than that seen after the application of a crystalline suspension). This was due to the ANC particles coming into contact with epithelial cells in a more efficient manner after the pulmonary application of the ANC powder than after the intestinal application of the ANC suspension. Therefore, the pulmonary insufflation of amorphous powder is a novel approach to improving the bioavailability of curcumin and might be a useful way of increasing the bioavailability of poorly water-soluble drugs, such as curcumin. PMID- 28987515 TI - Does exercise augment operant and Pavlovian extinction: A meta-analysis. AB - BACKGROUND: Exposure therapy, a behavioral approach to reduce symptomology in fear, anxiety, and drug-related psychiatric disorders, is based on learning and memory principles of extinction, and is subject to relapse. As such, it is important to find ways to enhance outcomes. One such way is through exercise. OBJECTIVES: Identify if exercise augments extinction behavior, and whether this depends on the experimental paradigm used (i.e. operant or Pavlovian) and/or stimulus (i.e. appetitive or aversive). Additionally, determine which moderating variables influence the effects of exercise on extinction learning. METHODS: A literature search was conducted and a Hedges' g calculation was employed to conduct a meta-analysis (metaSEM) using a structural equation modeling approach. This approach was chosen because of its ability to account for dependencies in effect sizes. RESULTS: We found a significant effect of exercise as an augmentation over extinction alone (g = 0.37, p < 0.001), with extinction paradigm (but not stimulus) producing a moderating effect (B = 0.43, p = 0.030). Data were then split by extinction paradigm, with operant extinction models having a significant effect (g = 0.55, p < 0.001), and number of extinction sessions moderating aggregate effects. Pavlovian models did not have significant overall effects (g = 0.11, p = 0.3976), but were moderated by the number of animals housed together and exercise after extinction. CONCLUSIONS: The effects of exercise on extinction learning are differentially modulated by the type of paradigm used, the number of extinction sessions, the timing of when exercise treatment was applied (after extinction), and the housing conditions. PMID- 28987514 TI - Analysis of PTPRK polymorphisms in association with risk and age at onset of Alzheimer's disease, cancer risk, and cholesterol. AB - The human receptor-type protein-tyrosine phosphatase kappa (PTPRK) gene is highly expressed in human brain and was previously associated with an increased risk of neuropsychiatric disorders and cancer. This study investigated the association of 52 single nucleotide polymorphisms (SNPs) in PTPRK with the risk and age at onset (AAO) of Alzheimer's disease (AD) in 791 AD patients and 782 controls. Our data analysis showed that five SNPs (top SNP rs4895829 with p = 0.0125) were associated with the risk of AD based on a multiple logistic regression (p < 0.05); while six SNPs (top SNP rs1891150 with p = 8.02 * 10-6) were associated with AAO by using a multiple linear regression analysis. Interestingly, rs2326681 was associated with both the risk and AAO of AD (p = 4.65 * 10-2 and 5.18 * 10-3, respectively). In a replication study, the results from family-based association test - generalized estimating equation (GEE) statistics and Wilcoxon test showed that seven SNPs were associated with the risk of AD (top SNP rs11756545 with p = 1.02 * 10-2) and 12 SNPs were associated with the AAO (top SNP rs11966128 with p = 1.39 * 10-4), respectively. One additional sample showed that four SNPs were associated with risk of cancer (top SNP rs1339197 with p = 4.1 * 10-3), 12 SNPs associated with LDL-cholesterol (top SNP rs4544930 with p = 3.47 * 10-3), and eight SNPs associated with total cholesterol (top SNP rs1012049 with p = 6.09 * 10-3). In addition, the AD associated rs4895829 was associated with the gene expression level in the cerebellum (p = 7.3 * 10-5). The present study is the first study providing evidence of several genetic variants within the PTPRK gene associated with the risk and AAO of AD, risk of cancer, LDL and total cholesterol levels. PMID- 28987517 TI - Reply to: "Pitfalls in the non-invasive assessment of liver fibrosis with eLIFT FMVCTE algorithm" and to "Application of the new eLIFT test for the non-invasive diagnosis of advanced liver fibrosis in people with type 2 diabetes". PMID- 28987516 TI - Cannabis can augment thrombolytic properties of rtPA: Intracranial hemorrhage in a heavy cannabis user. AB - Cannabis is one of the most commonly used illicit drugs in the United States and is considered to have several adverse health effects. There is evidence suggesting that its recreational use is associated with both increased cardio- and cerebrovascular events. Recently, multiple cases of ischemic and hemorrhagic strokes associated with cannabis use were reported in the literature (Goyal et al., 2017). It has been suggested that cannabis can affect cerebral auto regulation and vascular tone leading to vasoconstriction and acute ischemic stroke. However, hemorrhagic strokes, which are often seen with sympathomimetic illicit drugs (e.g. cocaine and amphetamines), have rarely been reported due to cannabis. Many cellular mechanisms within non-ischemic tissue post stroke may be augmented by heavy cannabis use. Here, we describe a rapid development of hemorrhage following thrombolytic therapy in a patient with heavy cannabis use with an ischemic stroke. PMID- 28987518 TI - Application of the new eLIFT test for the non-invasive diagnosis of advanced liver fibrosis in people with type 2 diabetes. PMID- 28987519 TI - Herbal tea consumption and the liver - All is not what it seems! PMID- 28987520 TI - Retreatment with direct-acting antivirals of genotypes 1-3-4 hepatitis C patients who failed an anti-NS5A regimen in real world. PMID- 28987521 TI - Heart Rate Response in Spectators of the Montreal Canadiens Hockey Team. AB - BACKGROUND: To our knowledge, heart rate responses have not previously been assessed in hockey fans. We quantified heart rate increases in spectators of the Montreal Canadiens, compared televised with live games, explored features associated with peak heart rates, and assessed whether increases correlate with a fan passion score. METHODS: Healthy adults were enrolled, with half attending live games and half viewing televised games. All subjects completed questionnaires and had continuous Holter monitoring. Intensity of the physical stress response was defined according to previously published heart rate index thresholds as mild (< 1.33), moderate (1.33-1.83), or vigorous (> 1.83). RESULTS: In 20 participants, 35% women, age 46 +/- 10 years, the heart rate increased by a median of 92% during the hockey game, from 60 (interquartile range, 54-65) beats per minute at rest to 114 (interquartile range, 103-129) beats per minute (P < 0.001). The heart rate increased by 110% vs 75% during live vs televised games (P < 0.001). Heart rate index (2.16 +/- 0.27 vs 1.73 +/- 0.15; P < 0.001) and percent maximum predicted heart rate attained (75% +/- 8% vs 58% +/- 7%; P < 0.001) were significantly higher during live vs televised games. Number of premature beats was nonsignificantly higher during live games (5 vs 1; P = 0.181). The fan passion score was not predictive of the heart rate response (P = 0.753). Peak heart rates most commonly occurred during overtime (40%) and scoring opportunities for (25%) and against (15%). CONCLUSIONS: It is exciting to watch the Montreal Canadiens! Viewing a live hockey game is associated with a heart rate response equivalent to vigorous physical stress and a televised game to moderate physical stress. PMID- 28987522 TI - Taking Hockey to Heart: Potential Coronary Risks of Watching Exciting Games. PMID- 28987523 TI - Hypoxia-induced activation of specific members of the NF-kB family and its relevance to pulmonary vascular remodeling. AB - BACKGROUND AND OBJECTIVE: Pulmonary Hypertension (pH) is a chronic progressive disease. Endothelial cells (EC) play a central and critical role in the initiation and progression of pH. The NF-kappaB family (NF-kappaB1 (p50/p105), NF kappaB2 (p52/p100), RelA (p65), RelB, and C-Rel) regulates a wide array of genes involved in inflammatory responses, cell proliferation, and survival. The involvement of specific NF-kappaB family members in the pathogenesis of hypoxia induced pH remains to be determined. The objective of this study was to assess the specific role of individual NF-kappaB family members in mediating endothelial cell responses to hypoxia and its downstream effect on smooth muscle cell proliferation. METHODS AND RESULTS: NF-kappaB family members' expression were selectively reduced by siRNA in human pulmonary microvascular endothelial cells. Cells were then exposed to hypoxia (1%) for 24h. Endothelin1, ICAM1 gene expression and Stat1 and Stat3 phosphorylation were assessed. Smooth muscle cells (SMC) proliferation was assessed by culturing them with EC conditioned media. Reduction of either NF-kappaB2 or RelA in EC, led to a significant decrease in Endothelin1 and ICAM1 gene expression. C-Rel knockdown resulted in a significant increase in phosphorylated STAT1; both C-Rel and RelA knockdown significantly decreased phosphorylated STAT3 in EC. There was a significant reduction in SMC proliferation, and AKT/ERK phosphorylation in SMC, when cultured in RelA knockdown, EC conditioned media. CONCLUSION: RelA in EC plays crucial role in hypoxia induced vascular remodeling and development of pH. Targeting RelA in EC alleviates SMC proliferation as well as inflammation related processes. PMID- 28987524 TI - Impact of a multicomponent hand hygiene-related intervention on the infectious risk in nursing homes: A cluster randomized trial. AB - BACKGROUND: The aim of this study was to assess the impact of a multifaceted hand hygiene (HH) program on the infectious risk in nursing homes (NHs). METHODS: This was a 2-arm cluster randomized trial; French NHs were allocated randomly to the intervention (13 NHs) or control (13 NHs) groups. The intervention consisted of implementing a bundle of HH-related measures over 1 year, including increased availability of alcohol-based handrub, HH promotion, staff education, and local work groups. The primary end point was the incidence rate of acute respiratory infections and gastroenteritis reported in the context of clustered cases episodes. Secondary end points were mortality, hospitalization, and antibiotic prescription rates. RESULTS: Baseline characteristics did not differ between groups. The overall handrub consumption was higher in the intervention group over the 1-year intervention period. Because of underreporting, data on the primary end points were of insufficient quality for analysis. Hospitalizations did not differ between the 2 groups. However, the intervention group showed significantly lower mortality (2.10 vs 2.65 per 100 residents per month, respectively; P = .003) and antibiotic prescriptions (5.0 vs 5.8 defined daily doses per 100 resident days, respectively; P < .001). These results were confirmed by the longitudinal multivariate analysis adjusted for NH and resident characteristics and for seasonality (mortality rate ratio, 0.76). CONCLUSIONS: A multifaceted HH intervention may have a short-term impact on mortality in NHs. Nevertheless, other strategies may remain necessary to reduce morbidity. PMID- 28987525 TI - Subgroup Analysis of Antibiotic Treatment for Skin Abscesses. AB - STUDY OBJECTIVE: Two large randomized trials recently demonstrated efficacy of methicillin-resistant Staphylococcus aureus (MRSA)-active antibiotics for drained skin abscesses. We determine whether outcome advantages observed in one trial exist across lesion sizes and among subgroups with and without guideline recommended antibiotic indications. METHODS: We conducted a planned subgroup analysis of a double-blind, randomized trial at 5 US emergency departments, demonstrating superiority of trimethoprim-sulfamethoxazole (320/1,600 mg twice daily for 7 days) compared with placebo for patients older than 12 years with a drained skin abscess. We determined between-group differences in rates of clinical (no new antibiotics) and composite cure (no new antibiotics or drainage) through 7 to 14 and 42 to 56 days after treatment among subgroups with and without abscess cavity or erythema diameter greater than or equal to 5 cm, history of MRSA, fever, diabetes, and comorbidities. We also evaluated treatment effect by lesion size and culture result. RESULTS: Among 1,057 mostly adult participants, median abscess cavity and erythema diameters were 2.5 cm (range 0.1 to 16.0 cm) and 6.5 cm (range 1.0 to 38.5), respectively; 44.3% grew MRSA. Overall, for trimethoprim-sulfamethoxazole and placebo groups, clinical cure rate at 7 to 14 days was 92.9% and 85.7%; composite cure rate at 7 to 14 days was 86.5% and 74.3%, and at 42 to 56 days, it was 82.4% and 70.2%. For all outcomes, across lesion sizes and among subgroups with and without guideline antibiotic criteria, trimethoprim-sulfamethoxazole was associated with improved outcomes. Treatment effect was greatest with history of MRSA infection, fever, and positive MRSA culture. CONCLUSION: Treatment with trimethoprim-sulfamethoxazole was associated with improved outcomes regardless of lesion size or guideline antibiotic criteria. PMID- 28987526 TI - Anterior lumbar sagittal alignment after anterior or lateral interbody fusion. AB - PURPOSE: Anterior or lateral interbody fusion is a treatment option for lumbar disc disease. A segmental change occurs after such surgery. This study was designed to evaluate the changes in the lumbar regional alignment after a single or two-level standalone anterior or lateral interbody fusion (ALIF or LLIF). METHODS: Data from patients referred to our institution between March 2013 and November 2015 for standalone ALIF or LLIF for low-grade isthmic spondylolisthesis or degenerative discopathy were retrospectively included in our analysis. Patients with a history of spinal fusion were excluded. Global and regional alignments were analyzed pre- and postoperatively. Pelvic tilt (PT), sacral slope (SS), sagittal vertical axis (SVA), lumbar lordosis (LL), index segmental lordosis (ISL) and L4S1 lordosis were compared. Three groups according to the pelvic incidence (PI) (low, normal and high) were separately analyzed then compared. RESULTS: Forty-one women and 27 men (mean age was 46 years; range 25 66) were included. The mean follow-up was 10.8 (range 3-34 months). The patients were globally well balanced preoperatively and remained after surgery (SVA stagnated from 16.76+/-28.42mm to 15.97+/-28.20mm, P=0.75). PT and LL did not vary. L4S1 lordosis, and ISL were significantly increased respectively from 30.56+/-8.59 to 34.58+/-7.47 (P=0.0026) and from 5.94+/-5.25 to 12.99+/-5.87 (P<0.0001) at latest follow-up. CONCLUSION: Despite effective changes in the segmental lordosis at the index levels, our findings suggest that one or two levels standalone ALIF or LLIF had no effect on the global balance and the lumbar lordosis. The three groups behaved similarly, the regional lordosis was redistributed in a better harmony (L4S1/LL ratio went up from 55% to 61%, P=0.01). STUDY TYPE: Retrospective study. LEVEL OF EVIDENCE: 4. PMID- 28987527 TI - Risk factors for radiographic progression of osteoarthritis after partial meniscectomy of discoid lateral meniscus tear. AB - INTRODUCTION: Partial meniscectomy has been preferred in the treatment of discoid lateral meniscus (DLM) with tear, rather than total or subtotal meniscectomy, which could lead to late radiographic degenerative changes. HYPOTHESIS: One or more risk factors contribute to radiographic progression of osteoarthritis after partial meniscectomy of DLM tear. MATERIAL AND METHODS: Inclusion criteria were consecutive patients who underwent arthroscopic surgeries for DLM tear from January 2005 to December 2010 by one surgeon. Exclusion criteria were preoperative osteoarthritis with KL grade 3 or more, osteochondritis dissecans, minimal width of meniscal remnant less than 6mm after meniscectomy, meniscal repair of an unstable discoid meniscus, age over 60years, loss to follow-up for a minimum of 5years and simultaneous surgery on articular cartilage or anterior cruciate ligament. According to the KL grade at the last follow-up, all enrolled knees were sorted into no progression to knee osteoarthritis (KL grade 1 or 2 - NOA) and progression to osteoarthritis (KL grade 3 or 4 - POA) groups. Multivariate logistic regression was used to analyze the risk factors of high grade osteoarthritis. RESULTS: In comparison with NOA group (n=135) and POA group (n=67), prolonged symptom duration, increased relative percentage of DLM thickness (RPDT) and the presence of horizontal tear were significant risk factors. The presence of horizontal tear (P=0.048, adjusted OR=19.364) was the strongest predictor, compared with prolonged symptom duration (P=0.030, adjusted OR=1.150) and increased RPDT (P=0.003, adjusted OR=1.377). DISCUSSION: Horizontal tear, prolonged symptom duration, and increased RPDT are significant risk factors for radiographic progression to high-grade osteoarthritis after partial meniscectomy of DLM tear with a minimum follow-up of 5years. LEVEL OF EVIDENCE: III, case-control study. PMID- 28987529 TI - A novel approach in the treatment of acute whiplash syndrome: Ultrasound-guided needle percutaneous electrolysis. A randomized controlled trial. AB - INTRODUCTION: Whiplash associated disorders are currently a common musculoskeletal problem. Besides the high incidence in western countries, the costs derived from prolonged treatment and medicolegal compensation, make this entity a challenging problem for clinicians and insurance companies. To date, no conservative treatment has shown clear superiority in the management of acute cases. HYPOTHESIS: Percutaneous needle electrolysis (PNE) is an effective approach for the treatment of Quebec type II acute whiplash syndrome (AWS). PNE consists in the application of brief galvanic currents into a damaged structure, producing a local controlled inflammatory response, with subsequent tissular healing enhancement. MATERIALS AND METHODS: One hundred AWS patients were randomized into: (a) standard physiotherapy intervention for AWS; (b) a standardized PNE protocol for AWS. Both groups were assessed for treatment outcome at the 5th week mark. RESULTS: Both groups showed a statistically significant improvement according to the Northwick Park Neck Questionnaire, visual analogic scale and pressure pain threshold. The improvement was similar in both groups, except for the pain pressure threshold, with a 56.6% reduction vs. 44.4% reduction in favour of the PNE group (P=0.035). In addition, the physio group consumed a mean treatment time of 20hours, while the PNE intervention averaged less than 1 hour in total. DISCUSSION: PNE can be considered as an effective treatment option for AWS. Importantly, the technique is highly cost effective, with limited equipment required and a notable treatment time reduction, compared to more comprehensive physiotherapy protocols. TYPE OF STUDY: Randomized controlled trial. LEVEL OF PROOF: 1b. PMID- 28987528 TI - The effectiveness of the Latarjet procedure for shoulder instability in patients with epilepsy. AB - INTRODUCTION: Powerful contractions during epileptic seizures may cause shoulder dislocation and instability. The aim of the study is to evaluate the functional and radiographic results of the Latarjet procedure for anterior shoulder dislocation in patients with epilepsy and compare the functional results of these patients with the results of patients without epilepsy. HYPOTHESIS: Is latarjet procedure effective in epileptic patients as non-epileptic patients with anterior shoulder instability? MATERIAL AND METHOD: Eleven shoulders of 9 patients with epileptic seizures causing anterior shoulder instability were evaluated retrospectively. All patients had a Latarjet procedure after neurologic evaluation and treatment arrangement. Epileptic seizures after the operation and shoulder dislocation after a seizure were investigated. For functional evaluation, ROWE, ASES and Constant scores were utilized whereas standard X-ray views were used for radiologic evaluation. The results of epileptic patients with Latarjet procedure were compared with non-epileptic patients (53 patients, 54 shoulders) for anterior shoulder instability. RESULTS: Three (33%) of the 9 epileptic patients had recurrent seizures after Latarjet procedure, whereas 1 of the 11 shoulders (9%) had dislocation after an epileptic seizure. Functional scores were found to be significantly improved in epileptic (P<0.001) and non epileptic patients (P<0.001). No significant differences for functional results were found between epileptic and non-epileptic patients after Latarjet procedure for anterior instability (P>0.05). One shoulder of 11 in the patients with epilepsy group (9%) and one shoulder of the 54 shoulders non-epileptic patients group (1.8%) had a redislocation. The rate of postoperative redislocation was significantly higher in patients with epilepsy (P=0.008). DISCUSSION: Epileptic patients have a high rate of recurrent seizures even with proper medical treatment. Significant functional improvements and shoulder stability may be achieved after Latarjet procedure in epileptic patients. These functional results were comparable with those of non-epileptic patients with Latarjet procedure for anterior shoulder instability. LEVEL OF EVIDENCE: III (case-control study). PMID- 28987530 TI - Parallel comprehensive two-dimensional gas chromatography. AB - We introduce an information rich analytical approach called parallel comprehensive two-dimensional gas chromatography (2GC*2GC). This parallel chromatography approach splits injected samples into two independent two dimensional column ensembles and provides two GC*GC separations by using contra directional thermal modulation. The first-dimension (1D) and second-dimension (2D) columns are connected using planar three-port microchannel devices, which are supplied with supplementary flow via two pressure controller modules. Precise carrier gas flow control at the junction of the 1D and 2D columns permits independent control of flow conditions in each separation column. The 2GC*2GC approach provides two entirely independent GC*GC separations for each injection. Analysis of hop (Humulus lupulus L.) essential oils is used to demonstrate the capability of the approach. The analytical performance of each GC*GC separation in the 2GC*2GC experiment is comparable to individual GC*GC separation with matching column configurations. The peak capacity of 2GC*2GC is about 2 times than that of single GC*GC system. The dual 2D chromatograms produced by this single detector system provide complementary separations and additional identification information by harnessing different selectivity provided by the four separation columns. PMID- 28987531 TI - Numerical study and theoretical performance limit of interconnected multi capillary gas chromatography columns with perfectly ordered pillar patterns. AB - We present the results of a theoretical and numerical study of the chromatographic performance of a novel type of microfabricated GC column. The column consists of an array of rectangular flow diverters (pillars), creating a network of perfectly ordered, interconnected and tortuous flow-through paths. Using van Deemter and kinetic plots of simulated band broadening data, we could demonstrate that the proposed column structure performs as a bundle of parallel open-tubular capillaries with rectangular cross-section, connected by a regular pattern of channel-intermixing points that allow compensating for inevitable channel-to-channel differences in migration velocity without adding any significant dispersion themselves. The established kinetic plots also allowed to propose design rules for the optimal distance between the pillars as a function of the desired separation efficiency and the available column pressure. The simulations also allowed establishing an expression for the plate height as a function of the velocity of the carrier gas. Results are also compared to the results of a recent experimental study. PMID- 28987532 TI - Development of an analytical method for the determination of polybrominated diphenyl ethers in mussels and fish by gas chromatography-Inductively coupled plasma mass spectrometry. AB - Six congeners of polybrominated diphenyl ethers (PBDEs): BDE 28, BDE 47, BDE 99, BDE 100, BDE 153 and BDE 154, were determined by a reliable and sensitive analytical method based on gas chromatography coupled to inductively coupled plasma mass spectrometry (GC-ICP-MS) in mussel and fish tissue samples. For their extraction, 30min of ultrasound-assisted extraction with a 25% aqueous solution of tetramethylammonium hydroxide (TMAH) and an additional 2h of mechanical shaking with tris(hydroxymethyl)aminomethane (Tris)-citrate buffer and iso-octane were applied. An effective cleaning, with minor solvent consumption, was achieved by passing the extract through a column filled with Florisil. PBDEs in the organic phase were quantified by GC-ICP-MS. Accuracy checks were performed by analyzing reference materials NIST SRM 2974a (freeze-dried mussel tissue) and SRM 1946 (fresh fish tissue homogenate) samples with a standard addition calibration method and by comparative analysis with species-specific isotope-dilution GC-ICP MS. Good agreement of results between the determined and certified values were obtained (recoveries lied between 94 and 105%). Limits of detection (LODs) expressed on wet weight (ww) basis were 0.003ngg-1 for BDE 28, 0.006ngg-1 for BDE 47, 0.008ngg-1 for BDE 99, 0.004ngg-1 for BDE100, 0.005ngg-1 for BDE 153 and 0.009ngg-1 for BDE 154. The analytical method was applied for the determination of PBDEs in marine mussels and fish samples from the northern Adriatic Sea and fish samples from the Sava River. Among the six PBDEs congeners determined, BDE 47, BDE 100 and BDE 99 were commonly detected in the samples analysed. PMID- 28987533 TI - Joint approximate diagonalization of eigenmatrices as a high-throughput approach for analysis of hyphenated and comprehensive two-dimensional gas chromatographic data. AB - The objective of the present work is development of joint approximate diagonalization of eigenmatrices (JADE) as a member of independent component analysis (ICA) family, for the analysis of gas chromatography-mass spectrometry (GC-MS) and comprehensive two-dimensional gas chromatography-mass spectrometry (GC*GC-MS) data to address incomplete separation problem occurred during the analysis of complex sample matrices. In this regard, simulated GC-MS and GC*GC-MS data sets with different number of components, different degree of overlap and noise were evaluated. In the case of simultaneous analysis of multiple samples, column-wise augmentation for GC-MS and column-wise super-augmentation for GC*GC MS was used before JADE analysis. The performance of JADE was evaluated in terms of statistical parameters of lack of fit (LOF), mutual information (MI) and Amari index as well as analytical figures of merit (AFOMs) obtained from calibration curves. In addition, the area of feasible solutions (AFSs) was calculated by two different approaches of MCR-BANDs and polygon inflation algorithm (FACPACK). Furthermore, JADE performance was compared with multivariate curve resolution alternating least squares (MCR-ALS) and other ICA algorithms of mean-field ICA (MFICA) and mutual information least dependent component analysis (MILCA). In all cases, JADE could successfully resolve the elution and spectral profiles in GC-MS and GC*GC-MS data with acceptable statistical and calibration parameters and their solutions were in AFSs. To check the applicability of JADE in real cases, JADE was used for resolution and quantification of phenanthrene and anthracene in aromatic fraction of heavy fuel oil (HFO) analyzed by GC*GC-MS. Surprisingly, pure elution and spectral profiles of target compounds were properly resolved in the presence of baseline and interferences using JADE. Once more, the performance of JADE was compared with MCR-ALS in real case. On this matter, the mutual information (MI) values were 1.01 and 1.13 for resolved profiles by JADE and MCR ALS, respectively. In addition, LOD values (MUg/mL) were respectively 1.36 and 1.24 for phenanthrene and 1.26 and 1.09 for anthracene using MCR-ALS and JADE which showed outperformance of JADE over MCR-ALS. PMID- 28987534 TI - Talking heads: Morphological variation in the human mandible over the last 500 years in the Netherlands. AB - The primary aim of this paper is to assess patterns of morphological variation in the mandible to investigate changes during the last 500 years in the Netherlands. Three-dimensional geometric morphometrics is used on data collected from adults from three populations living in the Netherlands during three time-periods. Two of these samples come from Dutch archaeological sites (Alkmaar, 1484-1574, n=37; and Middenbeemster, 1829-1866, n=51) and were digitized using a 3D laser scanner. The third is a modern sample obtained from MRI scans of 34 modern Dutch individuals. Differences between mandibles are dominated by size. Significant differences in size are found among samples, with on average, males from Alkmaar having the largest mandibles and females from Middenbeemster having the smallest. The results are possibly linked to a softening of the diet, due to a combination of differences in food types and food processing that occurred between these time periods. Differences in shape are most noticeable between males from Alkmaar and Middenbeemster. Shape differences between males and females are concentrated in the symphysis and ramus, which is mostly the consequence of sexual dimorphism. The relevance of this research is a better understanding of the anatomical variation of the mandible that can occur over an evolutionarily short time, as well as supporting research that has shown plasticity of the mandibular form related to diet and food processing. This plasticity of form must be taken into account in phylogenetic research and when the mandible is used in sex estimation of skeletons. PMID- 28987535 TI - Blood, sweat and plaster casts: Reviewing the history, composition, and scientific value of the Raymond A. Dart Collection of African Life and Death Masks. AB - This paper addresses the history, composition and scientific value of one of the most comprehensive facemask collections in Africa, the Raymond A. Dart Collection of African Life and Death Masks. Housed within the School of Anatomical Sciences at the University of the Witwatersrand (South Africa), it comprises 1110 masks (397 life, 487 death, 226 unknown). Life masks represent populations throughout Africa; death masks predominately southern Africa. Males preponderate by 75%. Recorded ages are error prone, but suggest most life masks are those of <35 year olds, death masks of 36+ year-olds. A total of 241 masks have associated skeletons, 209 presenting a complete skull. Life masks date between 1927 and c.1980s, death masks 1933 and 1963. This historical collection presents uncanny associations with outmoded typological and evolutionary theories. Once perceived an essential scientific resource, performed craniofacial superimpositions identify the nose as the only stable feature maintained, with the remaining face best preserved in young individuals with minimal body fat. The facemask collection is most viable for teaching and research within the history of science, specifically physical anthropology, and presents some value to craniofacial identification. Future research will have to be conducted with appropriate ethical considerations to science and medicine. PMID- 28987536 TI - Binding affinity toward human prion protein of some anti-prion compounds - Assessment based on QSAR modeling, molecular docking and non-parametric ranking. AB - The present study is based on the quantitative structure-activity relationship (QSAR) analysis of binding affinity toward human prion protein (huPrPC) of quinacrine, pyridine dicarbonitrile, diphenylthiazole and diphenyloxazole analogs applying different linear and non-linear chemometric regression techniques, including univariate linear regression, multiple linear regression, partial least squares regression and artificial neural networks. The QSAR analysis distinguished molecular lipophilicity as an important factor that contributes to the binding affinity. Principal component analysis was used in order to reveal similarities or dissimilarities among the studied compounds. The analysis of in silico absorption, distribution, metabolism, excretion and toxicity (ADMET) parameters was conducted. The ranking of the studied analogs on the basis of their ADMET parameters was done applying the sum of ranking differences, as a relatively new chemometric method. The main aim of the study was to reveal the most important molecular features whose changes lead to the changes in the binding affinities of the studied compounds. Another point of view on the binding affinity of the most promising analogs was established by application of molecular docking analysis. The results of the molecular docking were proven to be in agreement with the experimental outcome. PMID- 28987537 TI - Tuning the rheological properties of an ammonium methacrylate copolymer for the design of adhesives suitable for transdermal patches. AB - Eudragit(r) RL (EuRL) matrices have been proposed to release a drug to the skin. However, no information is available on both viscoelastic and adhesive properties of such compositions. This work focuses on the evaluation of both rheological and texture properties of EuRL differently plasticized with tributyl citrate (TBC) or triacetin (TRI) in order to design a pressure sensitive adhesive suitable for transdermal patch preparation. The patch adhesive properties (i.e. tack, peel adhesion and shear adhesion) as well as its in vitro biopharmaceutical performances were determined after loading ibuprofen, ketoprofen or flurbiprofen. The addition of 40-60% w/w TBC or 40-50% w/w TRI to EuRL permitted to obtain matrices with the desired adhesive properties. Moreover, the increase of plasticizer content and loading of the drug reduced the relaxation time (tauR). Consequently, the shear adhesion values decreased and the in vitro drug release constants (k) increased. Indeed, the k values from patches containing TBC were lower than the corresponding with TRI because of the lower fluidity of such matrices. In conclusion, the 60/40 EuRL/TBC binary blend is suitable for the design of transdermal patches since the in vitro permeability of the three selected drugs appeared comparable to those described in literature for marketed products. PMID- 28987538 TI - Development and evaluation of camptothecin loaded polymer stabilized nanoemulsion: Targeting potential in 4T1-breast tumour xenograft model. AB - Targeted delivery of anticancer agents is poised to improve cancer therapy, for which polymers can serve as targeting ligands or nanocarriers for chemotherapeutic agents. In this study, we have developed and evaluated the efficacy of a camptothecin (CPT)-loaded polymer stabilized nanoemulsion (PSNE) for the passive targeted delivery to breast cancer. Based on the pseudo-ternary phase diagrams, PSNEs were developed using capmul MCM:poloxamer 407 (4:1), solutol HS 15:simulsol P23 (1:2) and water. CPT polymer mixture was developed by solvent evaporation technique. The PSNEs were characterized for droplet size distribution, plasma protein adsorption, drug release, in-vivo targeting potential, hemolytic potential, cytotoxicity, genotoxicity, in-vivo biodistribution and CPT lactone ring stability. The developed PSNEs showed uniform droplet distribution, extended drug release (76.59+/-6.12% at 24h), acceptable hemolytic potential, significant cytotoxicity (IC50=176+/-4.3ng/mL) and genotoxicity against MCF-7 cancer cells but low DNA damage potential in human peripheral blood lymphocytes. The efficiency of PSNEs for the targeted delivery of CPT into the tumour regions was documented in 4T1-breast tumour xenografted BALB/c mice. In-vivo biodistribution study shows that 7105.84+/-568.46ng/g of CPT was passively targeted from PSNE to breast cancer tissue. About 80% of the lactone form was stable for 24h. Taken together, our study provides a promising strategy for developing PSNE-targeted drug delivery system for the breast cancer therapy. PMID- 28987539 TI - Statistical investigation of the full concentration range of fasted and fed simulated intestinal fluid on the equilibrium solubility of oral drugs. AB - Upon oral administration the solubility of a drug in intestinal fluid is a key property influencing bioavailability. It is also recognised that simple aqueous solubility does not reflect intestinal solubility and to optimise in vitro investigations simulated intestinal media systems have been developed. Simulated intestinal media which can mimic either the fasted or fed state consists of multiple components each of which either singly or in combination may influence drug solubility, a property that can be investigated by a statistical design of experiment technique. In this study a design of experiment covering the full range from the lower limit of fasted to the upper limit of fed parameters and using a small number of experiments has been performed. The measured equilibrium solubility values are comparable with literature values for simulated fasted and fed intestinal fluids as well as human fasted and fed intestinal fluids. The equilibrium solubility data range is statistically equivalent to a combination of published fasted and fed design of experiment data in six (indomethacin, phenytoin, zafirlukast, carvedilol, fenofibrate and probucol) drugs with three (aprepitant, tadalafil and felodipine) drugs not equivalent. In addition the measured equilibrium solubility data sets were not normally distributed. Further studies will be required to determine the reasons for these results however it implies that a single solubility measurement without knowledge of the solubility distribution will be of limited value. The statistically significant media factors which promote equilibrium solubility (pH, sodium oleate and bile salt) were in agreement with published results but the number of determined significant factors and factor interactions was fewer in this study, lecithin for example did not influence solubility. This may be due to the reduction in statistical sensitivity from the lower number of experimental data points or the fact that using the full range will examine media parameters ratios that are not biorelevant. Overall the approach will provide an estimate of the solubility range and the most important media factors but will not be equivalent to larger scale focussed studies. Further investigations will be required to determine why some drugs do not produce equivalent DoE solubility distributions, for example combined fasted and fed DoE, but this simply may be due to the complexity and individuality of the interactions between a drug and the media components. PMID- 28987540 TI - Serelaxin inhibits differentiation and fibrotic behaviors of cardiac fibroblasts by suppressing ALK-5/Smad2/3 signaling pathway. AB - Serelaxin, a recombinant form of human relaxin-2, is currently regarded as a novel drug for treatment of acute heart failure. However, whether therapeutic effects of serelaxin are achieved by inhibiting cardiac fibrosis remains unclear. In this study, we investigate effects of serelaxin on inhibiting cardiac fibrosis. Cardiac fibroblasts (CFs) were isolated from the hearts of adult rats. Effects of serelaxin on differentiation of CFs towards myofibroblasts (MFs) and their fibrotic behaviors after induction with TGF-beta1 were examined. Synthesis and degradation of collagens, secretion of IL-10, and expression of ALK-5 and p Smad2/3 of TGF-beta1-induced cells were assessed after treatment with serelaxin. Serelaxin inhibited differentiation of TGF-beta1-induced CFs towards MFs, and reduced proliferation and migration of the induced cells. Moreover, serelaxin down-regulated expression of collagen I/III and TIMP-2, and up-regulated expression of MMP-2 and MMP-9 in the cells. After treatment with serelaxin, activity of MMP-2 and MMP-9 and secretion of IL-10 increased, expression of ALK-5 and the level of Smad2/3 phosphorylation was reduced significantly. These results suggest that serelaxin can inhibit differentiation of TGF-beta1-induced CFs towards MFs, reduce production of collagens by suppressing ALK-5/Smad2/3 signaling pathway, and enhance extracellular matrix degradation by increasing MMP 2/TIMP-2 ratio and IL-10 secretion. Serelaxin may be a potential therapeutic drug for inhibiting cardiac fibrosis. PMID- 28987541 TI - Robo signaling regulates the production of cranial neural crest cells. AB - Slit/Robo signaling plays an important role in the guidance of developing neurons in developing embryos. However, it remains obscure whether and how Slit/Robo signaling is involved in the production of cranial neural crest cells. In this study, we examined Robo1 deficient mice to reveal developmental defects of mouse cranial frontal and parietal bones, which are derivatives of cranial neural crest cells. Therefore, we determined the production of HNK1+ cranial neural crest cells in early chick embryo development after knock-down (KD) of Robo1 expression. Detection of markers for pre-migratory and migratory neural crest cells, PAX7 and AP-2alpha, showed that production of both was affected by Robo1 KD. In addition, we found that the transcription factor slug is responsible for the aberrant delamination/EMT of cranial neural crest cells induced by Robo1 KD, which also led to elevated expression of E- and N-Cadherin. N-Cadherin expression was enhanced when blocking FGF signaling with dominant-negative FGFR1 in half of the neural tube. Taken together, we show that Slit/Robo signaling influences the delamination/EMT of cranial neural crest cells, which is required for cranial bone development. PMID- 28987542 TI - Establishment of twist-1 and TGFBR2 as direct targets of microRNA-20a in mesenchymal to epithelial transition of breast cancer cell-line MDA-MB-231. AB - Messenchymal to epithelial transition (MET) is a significant physiological phenomenon involved in embryogenesis and cancer. This study aims at investigating the mechanism of microRNA-20a (miR-20a) mediated regulation of mesenchymal to epithelial transition and identification of its direct target genes in breast cancer cell-line, MDA-MB-231. Reduced migratory and invasive property, altered cellular morphology along with reduced capability for attachment to basement membrane was acquired by over-expression of miR-20a in invasive MDA-MB-231 cell line initially expressing low level of this micro-RNA, indicating direct correlation between abundance of miR-20a and metastatic property. The switch from mesenchymal to epithelial cells mediated by miR-20a involved post-transcriptional down-regulation of twist1, which in turn controls downstream epithelial markers like E-cadherin, claudin and mesenchymal markers like N-cadherin, fibronectin, the crucial players of mesenchymal to epithelial transition (MET). Furthermore, another key component, TGF-beta and one of its receptors (TGFBR2) were found to be down-regulated by miR-20a. Additionally, reporter assay established that post transcriptional down-regulation of TGFBR2 occurred through direct binding of miR 20a to its 3'UTR, thus abrogating the TGF-beta signaling pathway resulting in inhibition of MET. Delineating the underlying molecular mechanism of miR-20a mediated MET and defining the target genes will help us to introduce a miRNA mediated effective therapeutic strategy against breast cancer. PMID- 28987543 TI - Ankle Evaluation in Active Rheumatoid Arthritis by Ultrasound: A Cross-Sectional Study. AB - Ankle joint evaluation is underestimated in many clinical and sonographic scores used for evaluation and follow-up of rheumatoid arthritis (RA) patients. Agreement on examination parameters is poor among sonographic scores that include the ankle joint. More effort is needed to detect the value of ankle joint examination in RA and assessment of ultrasonographic signs according to frequency, disease duration and activity. The objective of this study was to use ultrasound (US) to detect ankle involvement in active RA and to compare findings with disease duration, disease activity and assessment of ankle bone erosion. A total of 63 RA patients with active disease and 20 controls were included in the study. The tibiotalar and talonavicular joints were examined by US for synovitis and/or effusion in gray-scale and power Doppler modes. The anterior, lateral and posterior ankle tendons were examined for tenosynovitis and tendinosis. Mean age was 35.1 +/- 8.3 y, mean disease duration was 22.7 +/- 9.6 mo and the mean 28 joint Disease Activity Score-erythrocyte sedimentation rate was 3.05 +/- 0.66. Ankle involvement was seen in 28 patients (44.4%). The most frequent pathologies detected were tenosynovitis (30.2%), followed by synovitis (18.3%), erosion (8.7%) and tendinosis (4%). The earliest sonographic signs were tenosynovitis, followed by synovitis, erosion and tendinosis. The right ankle exhibited greater involvement than the left ankle, which was significant with respect to erosions (p = 0.009). The most common tendon affected by tenosynovitis was the tibialis anterior (22.2%), followed by the tibialis posterior (20.6%). Tenosynovitis, especially of the tibialis anterior and posterior, tibiotalar synovitis and erosions should be considered in future US ankle scores for the assessment of RA. PMID- 28987545 TI - Adverse events during and after per-oral endoscopic myotomy: prevention, diagnosis, and management. AB - Per-oral endoscopic myotomy (POEM) has surfaced as an effective endoscopic treatment modality for achalasia cardia (AC). Promising results in short- and mid term follow-up studies have increased the use of POEM for the management of AC. POEM can be safely performed in an endoscopy suit, and major adverse events (AEs) are uncommon. AEs encountered during POEM or during the perioperative period principally include insufflation-related AEs, mucosal injuries, bleeding, pain, and aspiration pneumonia. Most insufflation-related AEs do not require an active intervention and therefore should not be considered as AEs in the true sense. When management of AEs is required, most intraoperative AEs can be managed at the same time without untoward consequences. Occurrences of AEs lessen after completion of the learning curve. However, experience alone does not ensure "zero" incidence of AEs, and early recognition remains essential. Postoperative AEs, like leaks, delayed bleeding, and delayed mucosal perforations, may pose special challenges for diagnosis and management. There is no standardized classification system for grading the severity of AEs associated with POEM, resulting in wide variation in their reported occurrences. Uniform reporting of AEs is not only crucial to comprehensively analyze the safety of POEM but also for comparison with other established treatment modalities like Heller's myotomy. GERD is an important long-term AE after POEM. Unlike the perioperative AEs, little is known regarding the intraoperative or patient-related factors that influence the occurrence of post-POEM GERD. Large prospective studies with long term follow-up are required to determine the procedural factors associated with GERD after POEM. PMID- 28987544 TI - Adenoma detection rate influences the risk of metachronous advanced colorectal neoplasia in low-risk patients. AB - BACKGROUND AND AIMS: In individuals with either no or 1 to 2 nonadvanced adenomas, future risks of advanced colorectal neoplasia (AN) vary according to clinical risk factors. However, little is known about the association between the adenoma detection rate (ADR) and the risk for metachronous AN in patients with low-risk adenomas. METHODS: We identified 7171 participants with no or 1 to 2 nonadvanced adenomas at first-time screening colonoscopy. The risk of metachronous AN was investigated at surveillance colonoscopy, according to clinical characteristics and the ADR. RESULTS: In multivariate analysis the risk for metachronous AN was strongly associated with increasing age, male sex, increasing number of adenomas, and the ADR of the endoscopist. With the ADR modeled as a continuous variable, each 1.0% increase in the rate of ADR predicted a 3.0% decrease in the risk of metachronous AN (adjusted odds ratio [OR], .97; 95% confidence interval [CI], .95-.99). With the ADR modeled using a binary cut off (32%), the risk of metachronous AN was reduced in patients of endoscopists with an ADR >=32% (adjusted OR, .53; 95% CI, .35-.83). Moreover, the risk of metachronous AN was reduced (adjusted OR, .66; 95% CI, .46-.95) in patients of endoscopists with an ADR in the highest tertile, compared with patients of endoscopists with ADRs in the lowest tertile. The impact of ADR on metachronous AN was significant for patients with low-risk adenomas rather than patients with no adenoma. CONCLUSIONS: In patients with low-risk adenomas, the ADR of the endoscopist was inversely associated with the risk of metachronous AN. PMID- 28987546 TI - Increase in female faculty in American Society for Gastrointestinal Endoscopy sponsored programming over time. AB - BACKGROUND AND AIMS: Female representation in medicine is increasing across all levels of medical training, yet women hold fewer senior leadership positions than men. National recognition, including participation as faculty in society sponsored programs, is one component of academic advancement. The aim of this study was to characterize female representation among faculty in courses sponsored by the American Society for Gastrointestinal Endoscopy (ASGE). METHODS: We performed a retrospective review of demographic data, including faculty gender and role, year, and program type, from the ASGE database of its sponsored programs between 2009 and 2014. Female faculty rates were compared with the rate of female membership in the ASGE and by faculty role and course type over time. RESULTS: Between 2009 and 2014 there were a total of 2020 ASGE course faculty positions of which women comprised 19%. There was a significant increase in the proportion of women that served as course faculty over time (P < .0005). Female faculty participation exceeded the ASGE female domestic membership rate in all years. Women were more likely to serve as course directors than lecturers (25% vs 18%, P = .004) and to participate in smaller courses (P = .0003). CONCLUSIONS: We found an increase in female participation in ASGE programming over time, suggesting that specialty societies are making efforts to improve female representation at the national level. Future work should evaluate whether or not these opportunities translate into leadership roles for women within their own institutions or lead to promotions for women over time. PMID- 28987547 TI - Endoscopy in inflammatory bowel disease: advances in dysplasia detection and management. PMID- 28987548 TI - Efficacy and safety of endoscopic submucosal dissection for submucosal tumors of the colon and rectum. AB - BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) of colorectal submucosal tumors (SMTs) is becoming increasingly common; however, there have been few large consecutive studies analyzing its therapeutic efficacy and safety. The aim of this study was to evaluate the efficacy, safety, and long-term outcomes of ESD for colorectal SMTs. METHODS: This retrospective study included 412 consecutive patients with colorectal SMTs who underwent ESD at the Zhongshan Hospital of Fudan University from January 2008 to July 2014. Tumor histopathology, completeness of resection, adverse events, tumor recurrence, and distant metastasis were analyzed. RESULTS: Complete resection was achieved for 358 lesions (86.9%). Thirteen patients had serious adverse events (3.2%) including bleeding and perforation, and 28 patients (6.8%) had post-ESD electrocoagulation syndrome (PEECS). Because more ESDs for colorectal SMTs were performed by endoscopists, the rate of complete resection increased (78.5% vs 88.5%), and the rate of serious adverse events decreased (9.2% vs 2.0%). SMTs in the colon increased the risk of incomplete resection (19.6% vs 11.3%), serious adverse events (8.7% vs 1.6%), and PEECS (16.3% vs 4.1%). SMTs originating from the muscularis propria and sized >=20 mm increased the rate of PEECS (22.7% vs 5.9% and 31.3% vs 5.8%, respectively). CONCLUSION: ESD is effective for resection of colorectal SMTs and rarely causes serious adverse events. Tumor location and the experience of endoscopists influence the complete resection rate and the development of serious adverse events. ESD is feasible for large tumors and tumors in the muscularis propria, but this is associated with relatively high risks of adverse events. PMID- 28987550 TI - Implication of galanin gene rs948854 polymorphism in depressive symptoms in adolescents. AB - Genetic, social, and environmental conditions contribute to the development of depression, but the pathophysiological mechanisms are still unclear. Data accumulated in recent years provide significant evidence for a direct role of galanin (GAL). This study aimed to investigate the relation between SNPs in the galaninergic system and depressive symptoms in adolescents. A total of112 adolescents aged 10-18years participated in this study. The Children Depression Inventory (CDI) was used to evaluate depressive symptoms. The effects of rs948854 and rs4432027 SNPs, both located within the promoter region of the GAL gene, rs11665337 in the GALR1 receptor, and rs8836 in the GALR2 receptor on depressive symptoms were examined. The results indicated that 30.4% of the participants had depression. We found that girls were significantly more likely to be depressive than boys. Furthermore, rs948854 minor (G) allele was associated with depressive symptoms. Adolescents carrying the GG and AG genotype for the A/G (rs948854) SNP showed higher CDI scores than those carrying homozygous AA. The binomial logistic regression analysis revealed that adolescents carrying the GG genotype at SNP rs948854 had a higher likelihood of being depressive than adolescents carrying the AA or AG genotypes (P=0.033). Moreover, individuals whose mothers had a positive history for depression and who were sedentary were more likely to display depressive symptoms (P=0.013 and P=0.032, respectively). In conclusion, the SNP rs948854 in the GAL gene seems to be involved in the modulation of depressive state, especially in individuals with GG genotype. PMID- 28987549 TI - Potential impact of the 4CMenB vaccine on oropharyngeal carriage of Neisseria meningitidis. AB - The analysis of the potential impact of the meningococcal vaccines in asymptomatic carriers has become one of the key aspects in the evaluation of new vaccines and of their impact on disease control. An important step in this direction is provided by the analysis of the sequence variability and surface exposure of the 4CMenB (Bexsero(r)) vaccine antigens, as well as the cross reactivity of vaccine induced antibodies, in isolates from healthy carriers. The Spanish Reference Laboratory, in collaboration with the University Hospital Marques de Valdecilla in Santander (Spain), carried out a meningococcal carrier survey between May 2010 and April 2012 (population aged 4 to 19 years). The present study was done on 60 meningococcal carrier strains representative of the overall strain panel obtained and compared to invasive strains isolated in Spain in the same time. We found quantifiable levels of fHbp and NHBA expression and immunologic cross-reactivity in 10% and 75% of analyzed carrier strains, respectively, so the potential impact of the 4CMenB vaccine on Spanish asymptomatic carrier strains is expected to be mediated by the NHBA antigen. PMID- 28987551 TI - A Crus-Cial Discovery: Secondary Hypertension. PMID- 28987552 TI - Is Infection an Independent Risk Factor for Venous Thromboembolism? A Population Based, Case-Control Study. AB - BACKGROUND: The independent association of recent infection with venous thromboembolism is uncertain. The study aims were to test both overall infection (site unspecified) and specific infection sites as potential risk factors for deep vein thrombosis and pulmonary embolism adjusting for other known venous thromboembolism factors. METHODS: By using Rochester Epidemiology Project resources, we identified all Olmsted County, Minnesota, residents with objectively diagnosed incident deep vein thrombosis or pulmonary embolism over the 13-year period 1988 to 2000 (cases; n = 1303) and 1 to 2 residents without venous thromboembolism matched to each case on age, sex, and incident venous thromboembolism date (controls; n = 1494). Using conditional logistic regression, we tested recent infection and infection site(s) for an association with venous thromboembolism, adjusting for body mass index, smoking, current/recent hospitalization with/without surgery, nursing home confinement, active cancer, trauma/fracture, leg paresis, prior superficial vein thrombosis, transvenous catheter/pacemaker, ischemic heart disease, congestive heart failure, chronic lung or renal disease, serious liver disease, asthma, diabetes mellitus, hormone therapy, and pregnancy/postpartum. RESULTS: A total of 513 cases (39.4%) and 189 controls (12.7%) had an infection in the previous 92 days (odds ratio, 4.5; 95% confidence interval, 3.6-5.5; P < .0001). In a multivariable analysis adjusting for common venous thromboembolism risk factors, pneumonia and symptomatic urinary tract, oral, intra-abdominal, and systemic bloodstream infections were associated with significantly increased odds of venous thromboembolism. CONCLUSIONS: Infection as a whole and specific infection sites in particular are independent risk factors for venous thromboembolism and should be considered as potential indications for venous thromboembolism prophylaxis. PMID- 28987553 TI - seco-Tiaminic acids B and C: Identification of two novel 3,4-seco-tirucallane triterpenoids isolated from the root of Entandrophragma congoense (Meliaceae). AB - Chemical investigation of the roots of Entandrophragma congoense (Meliaceae) led to the isolation of two new 3,4-seco-tirucallane triterpenes, namely seco tiaminic acids B and C (1 and 2) together with nine known compounds: 3,4 secotirucalla-21-formyl-23-oxo-4(28),7,24-trien-3-oic acid (3), methyl angolensate (4), molucensin N (5), molucensin O (6), piscidinol A (7), 7alpha,20(S)-dihydroxy-4,24(28)-ergostadien-3-one (8), 24-methylene-cholest-5-en 3beta,7alpha-diol (9), entilin A (10), and entilin B (11). Their structures were determined using extensive spectroscopic methods including 1D and 2D NMR, HRMS, and CD analyses; new results were compared to existing data in the literature. The two newly identified seco-tiaminic acids showed moderate antiplasmodial and cytotoxic activities against a chloroquine-sensitive strain of the malaria parasite (Plasmodium falciparum NF54) and were cytotoxic toward an L6 rat skeletal myoblast cell line, respectively. PMID- 28987554 TI - Genetic transformation of the white-rot fungus Dichomitus squalens using a new commercial protoplasting cocktail. AB - D. squalens, a white-rot fungus that efficiently degrades lignocellulose in nature, can be used in various biotechnological applications and has several strains with sequenced and annotated genomes. Here we present a method for the transformation of this basidiomycete fungus, using a recently introduced commercial ascomycete protoplasting enzyme cocktail, Protoplast F. In protoplasting of D. squalens mycelia, Protoplast F outperformed two other cocktails while releasing similar amounts of protoplasts to a third cocktail. The protoplasts released using Protoplast F had a regeneration rate of 12.5% (+/-6 SE). Using Protoplast F, the D. squalens monokaryon CBS464.89 was conferred with resistance to the antibiotics hygromycin and G418 via polyethylene glycol mediated protoplast transformation with resistance cassettes expressing the hygromycin phosphotransferase (hph) and neomycin phosphotransferase (nptII) genes, respectively. The hph gene was expressed in D. squalens using heterologous promoters from genes encoding beta-tubulin or glyceraldehyde 3-phosphate dehydrogenase. A Southern blot confirmed integration of a resistance cassette into the D. squalens genome. An average of six transformants (+/-2 SE) were obtained when at least several million protoplasts were used (a transformation efficiency of 0.8 (+/-0.3 SE) transformants per MUg DNA). Transformation of D. squalens demonstrates the suitability of the Protoplast F cocktail for basidiomycete transformation and furthermore can facilitate understanding of basidiomycete gene function and development of improved strains for biotechnological applications. PMID- 28987555 TI - Characterization of 13 polymorphic microsatellite loci in the Japanese land leech. AB - We developed 13 polymorphic microsatellite loci of the Japanese land leech (Haemadipsa japonica; Haemadipsidea) using an Illumina MiSeq sequencing approach. A total of 42,064 nuclear DNA contigs were filtered for microsatellite motifs, among which 30,873 simple sequence repeat loci were identified. From these sequences, we selected 30 primer sets, and 13 of these loci were successfully amplified. Polymorphism of the 13 loci was tested using 16 individuals sampled from sixteen populations across Japan. The number of alleles and polymorphism information content varied from 5 to 17 and 0.335 to 0.883, respectively, and observed and expected heterozygosity values ranged from 0.143 to 0.875 and 0.349 to 0.893, respectively, indicating that these loci are polymorphic. Furthermore, we established useful multiplex PCR using these loci. The 13 microsatellite loci described in this paper are the first nuclear microsatellite markers for a land leech species. PMID- 28987556 TI - Taenia crassiceps antigens induce a Th2 immune response and attenuate injuries experimentally induced by neurotoxoplasmosis in BALB/c mice. AB - Toxoplasma gondii is a pathogenic agent responsible for causing both systemic and local disease which elicits a typically pro-inflammatory, Th1 immune response. Taenia crassiceps antigen induces a Th2 immune response that immunomodulates Th1 based infections. Therefore the aim of this study was to evaluate whether T. crassiceps cysticerci antigens are able to modulate the inflammatory response triggered in experimental neurotoxoplasmosis (NT). BALB/c mice were inoculated with T. gondii cysts and/or cysticerci antigens and euthanized at 60 and 90days after inoculation (DAI). The histopathology of the brains and cytokines produced by spleen cells culture were performed. The animals from the NT group, 90DAI (NT90), presented greater intensity of lesions such as vasculitis, meningitis and microgliosis and cytokines from Th1 profile characterized by high levels of IFN gamma. While in the T. crassiceps antigens group, 60DAI, there were more discrete lesions and high levels of IL-4, a Th2 cytokine. In the NT co-inoculated with cysticerci antigens group the parenchyma lesions were more discrete with lower levels of IFN-gamma and higher levels of IL-4 when compared to NT90. Therefore the inoculation of T. crassiceps antigens attenuated the brain lesions caused by T. gondii inducing a Th2 immune response. PMID- 28987557 TI - Stapled anastomosis versus hand-sewn anastomosis of gastro/duodenojejunostomy in pancreaticoduodenectomy: A systematic review and meta-analysis. AB - BACKGROUND: Controversy exists regarding the best anastomotic method for pancreaticoduodenectomy (PD). We aimed to evaluate the perioperative outcomes of PD with stapled anastomosis (SA) versus hand-sewn anastomosis (HA) of gastrojejunostomy or duodenojejunostomy. METHODS: We conducted a systematic search of electronic information sources, including MEDLINE; EMBASE; CINAHL; the Cochrane Central Register of Controlled Trials (CENTRAL); the World Health Organization International Clinical Trials Registry; ClinicalTrials.gov; ISRCTN Register, and bibliographic reference lists. We applied a combination of free text and controlled vocabulary search adapted to thesaurus headings, search operators and limits in each of the above databases. Delayed gastric emptying (DGE), postoperative pancreatic fistula (POPF), anastomotic bleeding, anastomotic leak, intra-abdominal abscess and mortality were defined as the outcome parameters. Combined overall effect sizes were calculated using fixed-effect or random-effects models. RESULTS: We identified 1 randomised controlled trial (RCT) and 5 observational studies reporting a total of 890 patients who underwent PD with SA (n = 300) or conventional HA (n = 590). Our analysis demonstrated that SA significantly reduced postoperative DGE (OR: 0.37, 95% CI 0.25-0.54, P < 0.00001) but significantly increased anastomotic bleeding (OR: 13.4, 95% CI 2.96-57.41, P = 0.0007) compared to HA. No significant difference was found in POPF (OR: 0.83, 95% CI 0.56-1.21, P = 0.33); anastomotic leak (OR: 0.50, 95% CI 0.09-3.79, P = 0.58); intra-abdominal abscess (OR: 1.39, 95% CI 0.71-2.70, P = 0.34); or mortality (RD: -0.01, 95% CI 0.03-0.02, P = 0.65) between two groups. CONCLUSIONS: Our analysis demonstrated that compared to conventional HA, SA may be associated with lower incidence of DGE after PD without increasing the risk of clinically significant POPF, anastomotic leak or mortality. However, it is associated with higher rate of anastomotic bleeding which mandates careful and precise haemostasis of the stapled line. Considering the current limited evidence, no definitive conclusion can be drawn. Future research is required. PMID- 28987558 TI - Endoscopic resection versus radical gastrectomy for early gastric cancer in Asia: A meta-analysis. AB - BACKGROUND: To compare the efficacy and safety of endoscopic resection (ER) and radical gastrectomy (RG) for early gastric cancer (EGC) in Asia. MATERIALS AND METHODS: We systematically searched relevant articles published before September 1, 2017. We evaluated the quality of the included non-randomized studies using the Newcastle-Ottawa Scale (NOS). Meta-analysis was carried out using RevMan 5.3 software. The odds ratio (OR) with 95% confidence intervals (CI) were used for the dichotomous data. RESULTS: Fifteen retrospective studies were included in this analysis (3737 patients in the ER group and 4246 patients in RG group). No significant differences in the three-year survival rate (OR, 0.87; 95%CI, 0.50 1.53) and five-year survival rate (OR, 0.81; 95%CI, 0.58-1.13) between the ER and RG groups were observed. Although patients undergoing ER had a higher risk of recurrence (OR, 6.07; 95%CI 4.17-8.84) and the occurrence of metachronous cancer (OR, 8.35; 95%CI, 5.48-12.75), recurrent or metachronous gastric cancers following ER were successfully detected and removed using the endoscopic technique. Higher recurrence in the ER group may be associated with its lower en bloc resection rate (OR, 0.05; 95%CI, 0.02-0.14) and complete resection rate (OR, 0.03; 95%CI, 0.01-0.08). Importantly, although the three-year survival and five year survival were similar in the two groups, the complication rate in the ER group was significantly lower than that in the RG group. CONCLUSION: ER is a good choice for patients with small EGC lesions (<=2 cm) without lymph node metastasis, especially in elderly patients with various medical comorbidities and in patients who cannot tolerate abdominal surgery or who meet the criteria but decline surgery. In contrast, RG is recommended when the diameter of the tumor is large (>2 cm) and preoperative examination suggests the possible presence of lymph node metastasis. PMID- 28987559 TI - Acid attacks: A new public health pandemic in the west? PMID- 28987560 TI - Outcomes of pelvic exenteration for recurrent and primary locally advanced rectal cancer. AB - BACKGROUND: Pelvic exenteration is the only radical treatment for locally advanced (ARC) or recurrent (RRC) rectal cancers. The long-term results of the procedure are variably reported in the literature, with recent series suggesting similar survival between ARC and RRC. The study aimed to analyze and compare the long-term survival and perioperative outcomes of patients undergoing pelvic exenteration for ARC and RRC in a tertiary center. MATERIALS AND METHODS: This was a retrospective analysis of prospectively collected data. Comparison of variables was performed using Chi-square, Fisher's exact or Wilcoxon rank sum test as appropriate. The Kaplan Meier method was used to analyze the disease-free survival (DFS) and the log-rank test to compare the two groups. RESULTS: Since 2002, 46 patients underwent pelvic exenteration for ARC (28, 60.9%) and RRC (18, 39.1%). The groups had comparable characteristics, perioperative results, including postoperative complications, and rate of adjuvant chemotherapy. A R0 resection was obtained in 71.4% and 55.6% (p 0.41) and a T4 stage was diagnosed in 75% and 94.4% (p 0.22) of ARC and RRC patients, respectively. After a median follow-up time of 32.5 and 56.6 months (p 0.01), the 5-year DFS was significantly lower in the RRC group (23.6 vs 46.2%, p 0.006), even after exclusion of R1 cases (30 vs 54.5%, p 0.044). CONCLUSION: The long-term disease free survival of patients undergoing pelvic exenteration is significantly worse when the procedure is performed for RRC, regardless of the tumor involvement of the resection margins. PMID- 28987561 TI - Therapeutic significance and indications of pulmonary metastasectomy for hepatocellular carcinoma following liver resection. AB - BACKGROUND: To explore the therapeutic significance and indications of pulmonary metastasectomy (PMT) in hepatocellular carcinoma (HCC) patients with pulmonary metastasis (PM) following liver resection (LR). PATIENTS AND METHODS: PM-HCC patients who underwent LR were retrospectively enrolled, and survival outcomes and prognostic factors were analyzed. Patients were divided into PMT and non-PMT group, and propensity score matching (PSM) analysis was used for survival comparison. Prognostic analysis and survival comparisons were performed specifically in PMT patients. RESULTS: Ninety-seven patients were enrolled, among which twenty-six underwent PMT while seventy-one did not. Survival outcome was superior in PMT group compared to non-PMT group (33.5 vs. 10.5 months) (p = 0.003), while no statistical difference was found after PSM analysis (33.5 vs. 11.2 months) (p = 0.138). Synchronous PM-HCC, serum alpha fetal protein>=400 ng/ml at PM diagnosis, no intrahepatic treatments (LR, ablation or transarterial chemoembolization) after LR, intrahepatic recurrence or metastasis at repeated PM diagnosis were inferior independent prognostic factors in PMT patients (p < 0.05). Superior survival outcomes were seen in candidate PMT patients when corresponding indications were satisfied (p = 0.014, p = 0.005). CONCLUSION: PMT might provide potential survival benefits in well selected PM-HCC patients who underwent LR. Well designed, multi-institutional studies with larger patient number were still to be required. PMID- 28987562 TI - The revision of 8th edition TNM stage criteria is more accurate in prediction postoperative survival for SCLC patients. AB - OBJECTIVES: The 8th edition TNM lung cancer classification was enacted in January 2017. An important change is the old T2a was revised to new T2a and T2b. Whether a postoperative survival difference exists between the two stages is still undefined. The purpose of this study is to investigate the postoperative outcomes of small cell lung cancer (SCLC) patients and compare the survival difference between the two stages. METHODS: Data of patients with SCLC who underwent surgery between October 2005 and August 2013 at our institute were reviewed. A total number of 194 patients were enrolled and were reclassified according to the 8th edition TNM stage. Survival was determined by Kaplan-Meier analysis, the log-rank test was used to compare survival differences. RESULTS: Surgical resection included 165 lobectomy or bilobectomy, 19 sublobectomy and 10 pneumonectomy. There were 159 patients received chemotherapy, 35 underwent surgery alone. The 5 year survival rate and median survival time (MST) of whole group was 34.5% and 45 months. For patients who received similar therapy (surgery plus chemotherapy) in N0 stage, the MST of T2a stage was 83 months, significantly longer than 62 months in T2b stage (P = 0.017). CONCLUSIONS: In the 8th edition TNM lung cancer stage criteria, the postoperative survival of T2a is superior to T2b for non-metastatic SCLC at N0 stage. PMID- 28987563 TI - Prospective validation of a preoperative risk score model based on pancreatic texture to predict postoperative pancreatic fistula after pancreaticoduodenectomy. AB - BACKGROUND: In 2015, basing on objective preoperative factors related to pancreas remnant texture (body mass index, Wirsung duct size and preoperative diagnosis), we proposed a score model to predict the risk of postoperative pancreatic fistula after partial pancreatectomies. The aim of the present study was to prospectively validate this preoperative predictive risk score for postoperative pancreatic fistula after pancreaticoduodenectomy. METHODS: Prospective study of consecutive patients who underwent pancreaticoduodenectomy in which a preoperative risk score, based on factors related to the pancreatic texture, was calculated. The risk score model was tested by comparison with subjective intraoperative assessment of the pancreas remnant texture and drain amylase value on postoperative day 1. Sensitivity, specificity, positive and negative likelihood ratio and area under the curve were calculated. RESULTS: Eighty-four patients who underwent pancreaticoduodnectomy were analyzed. Clinically relevant pancreatic fistulas rate was 40.6%. The risk score model with a cut-off of 6 increased the odds of pancreatic fistula approximately 3 fold but it was not independently related to it. On the contrary, considering a cut-off of 5, the risk score model increased the odds of pancreatic fistula 11-16 fold and it was independently related to it. The new risk score model and pancreatic texture had high sensitivity (97% and 88%, respectively) and low specificity (34% and 60%, respectively) while the amylase drain value had low sensitivity (44%) and high specificity (92%). CONCLUSIONS: The preoperative risk score model with a cut-off of 5 was a useful predictor of clinically relevant pancreatic fistula after pancreaticoduodenectomy. The drain amylase value represents a complementary factor to the risk score in predicting a pancreatic fistula. PMID- 28987564 TI - Roles of CSGalNAcT1, a key enzyme in regulation of CS synthesis, in neuronal regeneration and plasticity. AB - Chondroitin sulfate (CS) is a sulfated glycosaminoglycan composed of a long chain of repeating disaccharide units that are attached to core proteins, resulting in CS proteoglycans (CSPGs). In the mature brain, CS is concentrated in perineuronal nets (PNNs), which are extracellular structures that surround synapses and regulate synaptic plasticity. In addition, CS is rapidly synthesized after CNS injury to create a physical and chemical barrier that inhibits axon growth. Most previous studies used a bacterial CS-degrading enzyme to investigate the physiological roles of CS. Recent studies have shown that CS is synthesized by more than 15 enzymes, all of which have been characterized in vitro. Here we focus on one of those enzymes, CSGalNAcT1 (T1). We produced T1 knockout mice (KO), which show extensive axon regeneration following spinal cord injury, as well as the loss of onset of ocular dominance plasticity. These results from T1KO mice suggest important roles for extracellular CS in the brain regarding neuronal plasticity and axon regeneration. PMID- 28987565 TI - Genotoxic effects of vinclozolin on the aquatic insect Chironomus riparius (Diptera, Chironomidae). AB - Vinclozolin (Vz) is a pollutant found in aquatic environments whose antiandrogenic effects in reproduction are well known in mammals. Although its reproductive effects have been less studied in invertebrates, other effects, including genotoxicity, have been described. Therefore, in this work, we studied the genotoxic effects of Vz in the freshwater benthic invertebrate Chironomus riparius. DNA damage was evaluated with the comet assay (tail area, olive moment, tail moment and % DNA in tail), and the transcriptional levels of different genes involved in DNA repair (ATM, NLK and XRCC1) and apoptosis (DECAY) were measured by RT-PCR. Fourth instar larvae of C. riparius, were exposed to Vz for 24 h at 20 and 200 MUg/L. The Vz exposures affected the DNA integrity in this organism, since a dose-response relationship occurred, with DNA strand breaks significantly increased with increased dose for tail area, olive moment and tail moment parameters. Additionally, the lower concentration of Vz produced a significant induction of the transcripts of three genes under study (ATM, NLK and XRCC1) showing the activation of the cellular repair mechanism. In contrast, the expression of these genes with the highest concentration were downregulated, indicating failure of the cellular repair mechanism, which would explain the higher DNA damage. These data report for the first time the alterations of Vz on gene transcription of an insect and confirm the potential genotoxicity of this compound on freshwater invertebrates. PMID- 28987566 TI - Urinary level of triclosan in a population of Chinese pregnant women and its association with birth outcomes. AB - Triclosan (TCS) is a suspected endocrine disrupting chemical which is widely used in consumer products as an antibacterial agent. But findings in human studies focusing on the fetal developmental effects of prenatal TCS exposure were rare and inconsistent. This study aimed to determine maternal urinary TCS and investigate its association with birth outcomes. Pregnant women (n = 1006) were randomly selected from the prospective Healthy Baby Cohort (HBC) enrolled in 2014. TCS levels were determined in maternal urine samples collected at delivery and recorded birth outcomes were obtained from the medical records. Multiple linear regressions were applied to evaluate associations of maternal urinary TCS levels with birth outcomes including birth weight, birth length, and gestational age. Logistic regressions were used to evaluate associations with preterm birth, late term birth, and low birth weight. The geometric mean concentrations for TCS and specific gravity (SG) adjusted TCS in maternal urines were 0.73, 0.78 ng/mL, respectively. In the crude model, one ln-unit increase of urinary SG-adjusted TCS concentration was associated with a 0.30-day [95% confidence interval (CI): 0.00, 0.60] increase in gestational age; however, the associations were not statistically significant after adjustment for covariates. No significant associations of SG-adjusted TCS concentrations with birth weight and birth length were observed. Maternal SG-adjusted TCS concentrations were not related to preterm birth, late term birth, and low birth weight (all p > 0.10). Our findings reported a relatively low level of TCS among Chinese pregnant women. With such exposure level, we did not find strong evidence for associations between maternal TCS exposure and birth outcomes. Longitudinal studies concerning about different potential effects of TCS on perinatal health are necessary. PMID- 28987567 TI - Incidence of marine debris in cetaceans stranded and bycaught in Ireland: Recent findings and a review of historical knowledge. AB - Interactions between marine mammals and plastic debris have been the focus of studies for many years. Examples of interactions include entanglement in discarded fishing items or the presence of ingested debris in digestive tracts. Plastics, including microplastics, are a form of marine debris globally distributed in coastal areas, oceanic waters and deep seas. Cetaceans which strand along the coast present a unique opportunity to study interactions between animals with macro- and microplastics. A combination of novel techniques and a review of historical data was used to complete an extensive study of cetaceans interacting with marine debris within Irish waters. Of the 25 species of marine mammals reported in Irish waters, at least 19 species were reported stranded between 1990 and 2015 (n = 2934). Two hundred and forty-one of the stranded cetaceans presented signs of possible entanglement or interactions with fisheries. Of this number, 52.7% were positively identified as bycatch or as entangled in fisheries items, 26.6% were classified as mutilated and 20.7% could not be related to fisheries but showed signs of entanglement. In addition, 274 cetaceans were recorded as by-catch during observer programmes targeting albacore tuna. Post-mortem examinations were carried out on a total of 528 stranded and bycaught individuals and 45 (8.5%) had marine debris in their digestive tracts: 21 contained macrodebris, 21 contained microdebris and three had both macro- and microdebris. Forty percent of the ingested debris were fisheries related items. All 21 individuals investigated with the novel method for microplastics contained microplastics, composed of fibres (83.6%) and fragments (16.4%). Deep diving species presented more incidences of macrodebris ingestion but it was not possible to investigate this relationship to ecological habitat. More research on the plastic implications to higher trophic level organisms is required to understand the effects of these pollutants. PMID- 28987568 TI - Short-term effects of various ozone metrics on cardiopulmonary function in chronic obstructive pulmonary disease patients: Results from a panel study in Beijing, China. AB - BACKGROUND: Short-term exposure to ambient air pollution has been associated with lower pulmonary function and higher blood pressure (BP). However, controversy remains regarding the relationship between ambient multiple daily ozone (O3) metrics and cardiopulmonary health outcomes, especially in the developing countries. OBJECTIVES: To investigate and compare the short-term effects of various O3 metrics on pulmonary function, fractional exhaled nitric oxide (FeNO) and BP in a panel study of COPD patients. METHODS: We measured pulmonary function, FeNO and BP repeatedly in a total of 43 patients with COPD for 215 home visits. Daily hourly ambient O3 concentrations were obtained from central monitoring stations close to subject residences. We calculated various O3 metrics [daily 1-h maximum (O3-1 h max), maximum 8-h average (O3-8 h max) and 24-h average (O3-24 h avg)] based on the hourly data. Daily indoor O3 concentrations were estimated based on estimated indoor/outdoor O3 ratios. Linear mixed-effects models were used to estimate associations of various O3 metrics with cardiopulmonary function variables. RESULTS: An interquartile range (IQR) increase in ambient O3-8 h max (80.5 MUg/m3, 5-d) was associated with a 5.9% (95%CI: -11.0%, -0.7%) reduction in forced expiratory volume in 1 s (FEV1) and a 6.2% (95%CI: -10.9%, -1.5%) reduction in peak expiratory flow (PEF). However, there were no significant negative associations between ambient O3-1 h max, O3-24 h avg and FEV1, PEF. An IQR increase in ambient O3-1 h max (85.3 MUg/m3, 6-d) was associated with a 6.7 mmHg (95%CI: 0.7, 12.7) increase in systolic BP. The estimated indoor O3 were still significantly associated with reduction of FEV1 and PEF. No significant associations were found between various O3 metrics and FeNO. CONCLUSIONS: Our results provide clues for the adverse cardiopulmonary effects associated with various O3 metrics in COPD patients and highlight that O3 8 h max was more closely associated with respiratory health variables. PMID- 28987569 TI - Effect doses for protection of human health predicted from physicochemical properties of metals/metalloids. AB - Effect doses (EDs) of metals/metalloids, usually obtained from toxicological experiments are required for developing environmental quality criteria/standards for use in assessment of hazard or risks. However, because in vivo tests are time consuming, costly and sometimes impossible to conduct, among more than 60 metals/metalloids, there are sufficient data for development of EDs for only approximately 25 metals/metalloids. Hence, it was deemed a challenge to derive EDs for additional metals by use of alternative methods. This study found significant relationships between EDs and physicochemical parameters for twenty five metals/metalloids. Elements were divided into three classes and then three individual empirical models were developed based on the most relevant parameters for each class. These parameters included log-betan, DeltaE0 and Xm2r, respectively (R2 = 0.988, 0.839, 0.871, P < 0.01). Those models can satisfactorily predict EDs for another 25 metals/metalloids. Here, these alternative models for deriving thresholds of toxicity that could be used to perform preliminarily, screen-level health assessments for metals are presented. PMID- 28987570 TI - Effects of organic matter fraction and compositional changes on distribution of cadmium and zinc in long-term polluted paddy soils. AB - Soil particulate organic matter (POM) has rapid turnover and metal enrichment, but the interactions between organic matter (OM) and metals have not been well studied. The present study aimed to investigate changes in the OM concentration and composition of the POM fraction and their corresponding effects on metal distribution and extractability in long-term polluted paddy soils. Soil 2000-53 MUm POM size fractions had higher contents of C-H and C=O bonds, C-H/C=O ratios and concentrations of fulvic acid (FA), humic acid (HA), cadmium (Cd) and zinc (Zn) than the bulk soils. Cadmium and Zn stocks in soil POM fractions were 24.5 27.9% and 7.12-16.7%, respectively, and were more readily EDTA-extractable. Compared with the control soil, the 2000-250 MUm POM size fractions had higher organic carbon concentrations and C/N ratios in the polluted soils. However, there were no significant differences in the contents in C-H and C=O bonds or C H/C=O ratios of POM fractions among the control, slightly and highly polluted soils. In accordance with the lower contents of C=O bonds and FA and HA concentrations, the Cd and Zn concentrations in 250-53 MUm POM size fractions were lower than those in 2000-250 MUm POM size fractions. Enrichment of Cd in POM fractions increased with increasing soil pollution level. These results support the view that changes in the OM concentration and the size and composition of POM fractions play a key role in determining the distribution of Cd and Zn in paddy soils. PMID- 28987571 TI - Field trial of 2 calcium supplements on early lactation health and production in multiparous Holstein cows. AB - Our objectives were to measure serum Ca concentrations in the first 48 h postpartum in cows supplemented with oral Ca or subcutaneous Ca and nonsupplemented cows and evaluate the effect of these treatments on the incidence of metritis, displaced abomasum, mastitis, and early lactation disease (any of the diseases milk fever, retained placenta, metritis, or displaced abomasum), removal from the herd, pregnancy to first insemination, and average daily milk yield for the first 10 wk of lactation. We conducted 2 experiments on 1 commercial herd in New York State. In experiment 1, multiparous Holstein cows (n = 30) were blocked by parity (2 and >=3) and sequentially assigned at calving to nontreated control (CON, n = 10), subcutaneous administration of 500 mL 23% Ca gluconate at calving (SC, n = 10), or administration of an oral Ca bolus containing 43 g of calcium at calving and again 12 h later (OB, n = 10). Blood was collected before treatment and at 1, 2, 4, 8, 12, 24, and 48 h thereafter for measurement of serum total Ca concentration. In experiment 2, 1,478 multiparous Holstein cows were sequentially assigned by calving date to the same 3 treatments (CON, n = 523; SC, n = 480; OB, n = 475). In experiment 1, SC cows had greater Ca concentrations from 1 through 12 h post-treatment and OB cows had greater Ca concentrations at 1 and 24 h post-treatment compared with CON cows. We found no difference in risk of metritis, displaced abomasum, early lactation disease diagnosis, or pregnancy to first insemination among treatments. Treatment with SC or OB had no effect on average daily milk yield compared with CON cows (CON = 46.7 kg; SC = 47.1 kg; OB = 47.0 kg). Cows treated with SC or OB that had a high relative herd milk rank in the previous lactation were almost half as likely to be diagnosed with mastitis in the first 60 DIM compared with CON cows [risk ratio (RR)SC = 0.57, RROB = 0.54]; however, we found no difference in risk of mastitis among treatments for cows with low relative herd milk rank. Second-parity cows fed a negative prepartum dietary cation-anion difference ration and treated with SC or OB were more likely to be removed from the herd than CON cows (RRSC = 3.91, RROB = 4.72); this difference was not observed in second-parity cows fed a neutral prepartum dietary cation-anion difference ration or in parity >=3 cows. Although Ca supplementation increased serum Ca, this effect did not greatly improve milk production or health and reproductive outcomes. PMID- 28987572 TI - Genotype imputation in a tropical crossbred dairy cattle population. AB - The objective of this study was to investigate different strategies for genotype imputation in a population of crossbred Girolando (Gyr * Holstein) dairy cattle. The data set consisted of 478 Girolando, 583 Gyr, and 1,198 Holstein sires genotyped at high density with the Illumina BovineHD (Illumina, San Diego, CA) panel, which includes ~777K markers. The accuracy of imputation from low (20K) and medium densities (50K and 70K) to the HD panel density and from low to 50K density were investigated. Seven scenarios using different reference populations (RPop) considering Girolando, Gyr, and Holstein breeds separately or combinations of animals of these breeds were tested for imputing genotypes of 166 randomly chosen Girolando animals. The population genotype imputation were performed using FImpute. Imputation accuracy was measured as the correlation between observed and imputed genotypes (CORR) and also as the proportion of genotypes that were imputed correctly (CR). This is the first paper on imputation accuracy in a Girolando population. The sample-specific imputation accuracies ranged from 0.38 to 0.97 (CORR) and from 0.49 to 0.96 (CR) imputing from low and medium densities to HD, and 0.41 to 0.95 (CORR) and from 0.50 to 0.94 (CR) for imputation from 20K to 50K. The CORRanim exceeded 0.96 (for 50K and 70K panels) when only Girolando animals were included in RPop (S1). We found smaller CORRanim when Gyr (S2) was used instead of Holstein (S3) as RPop. The same behavior was observed between S4 (Gyr + Girolando) and S5 (Holstein + Girolando) because the target animals were more related to the Holstein population than to the Gyr population. The highest imputation accuracies were observed for scenarios including Girolando animals in the reference population, whereas using only Gyr animals resulted in low imputation accuracies, suggesting that the haplotypes segregating in the Girolando population had a greater effect on accuracy than the purebred haplotypes. All chromosomes had similar imputation accuracies (CORRsnp) within each scenario. Crossbred animals (Girolando) must be included in the reference population to provide the best imputation accuracies. PMID- 28987573 TI - Risk assessment modelling of fecal shedding caused by extended-spectrum cephalosporin-resistant Escherichia coli transmitted through waste milk fed to dairy pre-weaned calves. AB - Waste milk feeding is a common practice in dairy operations. Regardless of the benefits of this practice to the dairy farmers, concerns from the potential dissemination of antimicrobial-resistant bacteria through the gut and subsequent shedding by calves into the environment are increasing. In this study, we employed Monte Carlo simulation to assess the risk of shedding extended-spectrum cephalosporin-resistant Escherichia coli (ESC-R E. coli) caused by waste milk feeding in pre-weaned calves using an exponential dose-response model fit to data for E. coli O157:H7 in cattle. Data from pertinent studies were included in our model to predict the risk of shedding. The median (5th and 95th percentiles) for the daily risk of shedding ESC-R E. coli by calves fed only contaminated waste milk was predicted to be 2.9 * 10-3 (2.1 * 10-3, 3.7 * 10-3), representing a median daily risk of 29 out of 10,000 calves shedding ESC-R E. coli due to exclusive feeding of waste milk containing ESC-R E. coli. This median value was reduced by 94% when accounting for the proportion of waste milk that does not contain ESC-R E. coli. The overall risk of shedding ESC-R E. coli through the pre weaning period for farms that feed waste milk to calves was 5.7 * 10-3 (2.4 * 10 3, 1.1 * 10-2), representing 57 out of 10,000 calves. When accounting for the proportion of farms that do not feed waste milk, the pre-weaning period risk was reduced by 23%. By varying the prevalence of ESC-R E. coli in waste milk using values of 3, 1.5, and 1%, the daily risk of shedding decreased by factors of 50, 65, and 82%, respectively, which supports the reduction of contamination or discontinuation of feeding waste milk containing ESC-R E. coli as major mitigation measures to reduce the risk of shedding caused by ingestion of resistant bacteria. It is anticipated that the effects of antimicrobial residues in waste milk, which was not considered herein due to lack of data, would further increase risks. Although waste milk feeding to calves may be economically beneficial to the dairy farmers, there exists the risk of dissemination of ESC resistant bacteria into the environment. PMID- 28987574 TI - Invited review: Sustainable forage and grain crop production for the US dairy industry. AB - A resilient US dairy industry will be underpinned by forage and crop production systems that are economically, environmentally, and socially sustainable. Land use for production of perennial and annual forages and grains for dairy cattle must evolve in response to multiple food security and environmental sustainability issues. These include increasing global populations; higher incomes and demand for dairy and other animal products; climate change with associated temperature and moisture changes; necessary reductions in carbon and water footprints; maintenance of soil quality and soil nutrient concerns; and competition for land. Likewise, maintaining producer profitability and utilizing practices accepted by consumers and society generally must also be considered. Predicted changes in climate and water availability will likely challenge current feed and dairy production systems and their national spatial distribution, particularly the western migration of dairy production in the late 20th century. To maintain and stabilize profitability while reducing carbon footprint, particularly reductions in methane emission and enhancements in soil carbon sequestration, dairy production will need to capitalize on genetic and management innovations that enhance forage and grain production and nutritive value. Improved regional and on-farm integration of feed production and manure utilization is needed to reduce environmental nitrogen and phosphorus losses and mitigate greenhouse gas emissions. Resilient and flexible feed production strategies are needed to address each of these challenges and opportunities to ensure profitable feeding of dairy cattle and a sustainable dairy industry. PMID- 28987575 TI - Short communication: The effect of storage conditions and storage duration on milk ELISA results for pregnancy diagnosis. AB - The objective of this study was to evaluate the effect of storage temperature and time from sample collection to analysis on test classification of a commercially available ELISA for diagnosis of pregnancy using the measurement of pregnancy associated glycoproteins (PAG) in milk samples from dairy cows. Few studies have evaluated the effects of sample handling on milk PAG results. Using a repeated measures study design, we evaluated sample storage at 5 temperatures: 37 degrees C, 22 degrees C, 4 degrees C, -20 degrees C, or -80 degrees C. Sample aliquots from 45 cows (20 with a pregnant test result, 10 open, and 15 recheck) were stored for 4, 7, 14, 28, 60, 90, or 365 d. The measured PAG level was influenced by storage duration and condition. Samples stored for 365 d had a slightly increased PAG level, whereas samples stored for all other durations showed a slight decline in PAG level compared with the initial result. The reason for an increase in PAG level following long-term storage is not known. This will not affect dairy producers using the test but may be important in samples stored for research applications. The changes in PAG level were small and within the expected variation for this test. Fewer than 6% of samples changed in classification and, as expected, they were samples near the test interpretation cut-points. PMID- 28987576 TI - Genetic parameters for health traits using data collected from genomic information nucleus herds. AB - As with many other countries, data availability has been a limitation in Australia for developing breeding values for health traits. A genomic information nucleus of approximately 100 herds across the country, selected on the basis of their record keeping, has recently been established in Australia and is known as Ginfo. The objective of this study was to evaluate the feasibility of developing genomic breeding values for health traits using farmer-collected data from Ginfo herds. Having this genotyped population opens up opportunities to develop new genomic breeding values, such as dairy health traits. In these herds, the 4 most recorded groups of health diseases identified were mastitis, reproductive problems, lameness, and metabolic disorders with incidence levels of 16, 9, 2, and 1.5%, respectively. Heritability estimates from pedigree and genomic analysis ranged from 0.01 to 0.03 for mastitis, 0.005 to 0.02 for reproductive disorders, 0 to 0.02 for lameness, and 0.00 to 0.06 for metabolic disorders. However, although heritability is low, there is sufficient genetic variation to make genetic progress feasible (coefficient of variation ranging from 3 to 26.3%). Genetic correlations between health and milk production traits (0.08 to 0.48) and overall type (-0.00 to 0.57) are unfavorable, but favorable with other economical traits, such as fertility (0.10 to 0.51), survival (-0.16 to -0.37), and somatic cell count (0.07 to 0.55). For a genomic reference population of 11,458 cows, the reliability of genomic predictions is comparatively low (<30%), but is promising for health traits, such as mastitis (~30%) and a broader-based all disease trait (~28%), when bulls have daughters in the reference population, but not when they only have genomic information (0 to 18%). Further improvement of the reliabilities of health breeding values continues to be an important objective. The study has provided a good foundation for future research to develop breeding values for health traits. PMID- 28987577 TI - Predicting bull fertility using genomic data and biological information. AB - The genomic prediction of unobserved genetic values or future phenotypes for complex traits has revolutionized agriculture and human medicine. Fertility traits are undoubtedly complex traits of great economic importance to the dairy industry. Although genomic prediction for improved cow fertility has received much attention, bull fertility largely has been ignored. The first aim of this study was to investigate the feasibility of genomic prediction of sire conception rate (SCR) in US Holstein dairy cattle. Standard genomic prediction often ignores any available information about functional features of the genome, although it is believed that such information can yield more accurate and more persistent predictions. Hence, the second objective was to incorporate prior biological information into predictive models and evaluate their performance. The analyses included the use of kernel-based models fitting either all single nucleotide polymorphisms (SNP; 55K) or only markers with presumed functional roles, such as SNP linked to Gene Ontology or Medical Subject Heading terms related to male fertility, or SNP significantly associated with SCR. Both single- and multikernel models were evaluated using linear and Gaussian kernels. Predictive ability was evaluated in 5-fold cross-validation. The entire set of SNP exhibited predictive correlations around 0.35. Neither Gene Ontology nor Medical Subject Heading gene sets achieved predictive abilities higher than their counterparts using random sets of SNP. Notably, kernel models fitting significant SNP achieved the best performance with increases in accuracy up to 5% compared with the standard whole genome approach. Models fitting Gaussian kernels outperformed their counterparts fitting linear kernels irrespective of the set of SNP. Overall, our findings suggest that genomic prediction of bull fertility is feasible in dairy cattle. This provides potential for accurate genome-guided decisions, such as early culling of bull calves with low SCR predictions. In addition, exploiting nonlinear effects through the use of Gaussian kernels together with the incorporation of relevant markers seems to be a promising alternative to the standard approach. The inclusion of gene set results into prediction models deserves further research. PMID- 28987578 TI - Housing and management characteristics of calf automated feeding systems in the Upper Midwest of the United States. AB - Automated milk feeders are used by dairy producers to manage preweaned calves in group housing, but little is known about how these feeding systems are being used in the United States. To better understand how US dairy producers are operating these systems, this study investigated characteristics of barn design, environment, and management practices on 38 farms in the Upper Midwest of the United States via a questionnaire and on-farm measurements. Farms using automated feeders ranged in size from 7 to 300 calves on site. Natural ventilation was used on 50% of the farms, followed by barns with mechanical ventilation (39.5%), tunnel ventilation (7.9%), or outdoor facilities (sheltered plastic domes; 2.6%). Calves were kept in groups of 17.6 +/- 9.8 animals (range: 5.9 to 60.5) with an average space allowance of 4.6 +/- 2.0 m2/animal (range: 1.6 to 11.9). Calves on these farms received 3.7 +/- 0.75 L (range: 2 to 6) of colostrum, but 22% of the tested calves had serum total protein values lower than 5.0 g/dL. Calves had an initial daily allowance of 5.4 +/- 2.1 L (range: 3 to 15 L) of milk or milk replacer, rising to a peak amount of 8.3 +/- 2.0 L (range: 5 to 15 L) over 18 +/- 11.4 d (range: 0 to 44 d). Milk replacer was fed to calves on 68.4% of the farms compared with whole milk supplemented with nutrient balancer on 23.7% and whole milk alone on 7.9% of the farms. Calves were completely weaned at 56.8 +/- 9.0 d of age (range: 40 to 85.5) and 52.1 +/- 7.5 d (range: 40 to 79) since introduction into the group pen with the feeder. Notably, bacterial contamination of milk was common; the median coliform count was 10,430 cfu/mL (interquartile range: 233,111; range: 45 to 28,517,000) and standard plate count was 2,566,867 cfu/mL (interquartile range: 15,860,194; range 6,668 to 82,825,000) for samples collected from the feeder tube end (or feeder hose). Some areas of deficiency might be of concern as they might be influencing the success of using automated calf feeding systems. In particular, a better understanding of the dynamics of pathogen load is needed in both the group pen area and in the automated feeder unit itself, as these reservoirs represent significant risk to calf health and welfare. PMID- 28987579 TI - Mammary epithelium disruption and mammary epithelial cell exfoliation during milking in dairy cows. AB - The presence of mammary epithelial cells (MEC) in the milk of ruminants indicates that some MEC are shed from the mammary epithelium; however, the mechanisms that regulate the MEC exfoliation process are not known. Through the release of oxytocin, prolactin, and cortisol and through oxytocin-induced mechanical forces on the mammary epithelium, milking could participate in regulating the MEC exfoliation process. The aims of the present study were to determine the rate of MEC exfoliation throughout milking and to investigate its relationship to mammary epithelium integrity and milking-induced hormone release. Milk samples from 9 Holstein dairy cows producing 40.6 +/- 1.36 kg of milk/d were collected at the beginning (after 1 and 2 min), in the middle, and at the end of milking. Milk MEC were purified using an immunomagnetic method. Blood samples were collected before, during, and after milking, and the oxytocin, prolactin, and cortisol concentrations in the samples were measured. Tight junction opening was assessed by plasma lactose concentration and the Na+:K+ ratio in milk. The somatic cell count in milk varied during the course of milking; it decreased at the beginning of milking and then increased, reaching the highest values at the end of milking. Exfoliated MEC were present in all milk samples collected. The presence of MEC in the milk sample collected during min 1 of milking, likely corresponding to the cisternal milk fraction, suggests that MEC were exfoliated between milkings. The observed increase in the Na+:K+ ratio in milk and in the plasma concentration of lactose indicated that disruption of mammary epithelium integrity occurred during milking. The MEC exfoliation rate at milking was not correlated with the variables describing milking-induced prolactin release but was negatively correlated with cortisol release, suggesting that cortisol may play a role in limiting exfoliation. In conclusion, milking induced a disruption of the mammary epithelial barrier. Mammary epithelial cells may be continuously exfoliated between milkings or exfoliated during milking as a consequence of the oxytocin induced mechanical forces and the disruption of mammary epithelium integrity. PMID- 28987580 TI - Physically adjusted neutral detergent fiber system for lactating dairy cow rations. I: Deriving equations that identify factors that influence effectiveness of fiber. AB - Physically effective neutral detergent fiber (peNDF) is the fraction of neutral detergent fiber (NDF) that stimulates chewing activity and contributes to the floating mat of large particles in the rumen. Multiplying dietary NDF by particle size has been used as an estimate of peNDF. In re-evaluating the concept of peNDF, we compared the use of peNDF as dietary NDF * particle size with the use of individual NDF and particle size descriptors (physically adjusted NDF; paNDF) when used with other physical and chemical diet descriptors to predict dry matter (DM) intake (DMI), rumination time, and ruminal pH in lactating dairy cows. The purpose is to ultimately use these equations to estimate diet adequacy to maintain ruminal conditions. Each response variable had 8 models in a 2 (peNDF, paNDF) * 2 (diet, diet and ruminal factors) * 2 (DM, as fed basis) factorial arrangement. Particle size descriptors were those determined with the Penn State Particle Separator. Treatment means (n = 241) from 60 publications were used in backward elimination multiple regression to derive models of response variables. When available, peNDF terms entered equations. Models containing peNDF terms had similar or lower unadjusted concordance correlation coefficients (an indicator of similar or lower accuracy and precision) than did models without peNDF terms. The peNDF models for rumen pH did not differ substantially from paNDF models. This suggests that peNDF can account for some variation in ruminal pH; however, overt advantages of peNDF were not apparent. Significant variables that entered the models included estimated mean particle size; as fed or DM proportions retained on 19- and 8-mm sieves of the Penn State Particle Separator; DMI; dietary concentrations of forage; forage NDF; CP; starch; NDF; rumen-degraded starch and rumen-degraded NDF; and the interaction terms of starch * mean particle size, acid detergent fiber/NDF, and rumination time/DMI. Many dietary factors beyond particle size and NDF were identified as influencing the response variables. In conclusion, these results appear to justify the development of a modeling approach to integrate individual physical and chemical factors to predict effects on factors affecting rumen conditions. PMID- 28987581 TI - Effects of the level and duration of maternal diets with negative dietary cation anion differences prepartum on calf growth, immunity, and mineral and energy metabolism. AB - The objectives were to investigate the effects that maternal diets containing negative dietary cation-anion differences (DCAD) fed in the last 42 d of gestation may have on the acid-base status, hematology, mineral and energy metabolism, growth, and health of calves. The experiment was a randomized block design with a 2 * 2 factorial arrangement of 2 levels of negative DCAD (-70 or 180 mEq/kg) and 2 feeding durations (the last 21 d prepartum and the last 42 d prepartum). Bulls and heifers (n = 60) born to these dams were weighted at birth and fed 3.8 L of colostrum for their first feeding, and only heifers (n = 44, 9 12/treatment) were kept thereafter. Heifer body weight was also recorded at 21 d, 42 d, 62 d, 3 mo, and 6 mo of age. Blood was collected at birth, before colostrum feeding, and at 1, 2, 3, 21, and 42 d of age and assayed for minerals, metabolites, and cell counts. Heifers born to dams fed the last 42 d prepartum weighed 2.8 and 4.8 kg less at birth and 62 d, respectively, compared with calves born to dams fed the last 21 d prepartum; however, body weight at 3 and 6 mo of age was similar. Concentrations of ionized calcium did not differ among treatments at birth, but heifers born to -180 DCAD dams had increased blood concentrations at 3 d of age, whereas those born to -70 DCAD dams did not. At birth, heifers born to -180 DCAD dams experienced a subtle and transient metabolic acidosis (pH = 7.33 +/- 0.02; pCO2 = 53.0 +/- 2.4 mmHg; HCO3- = 27.6 +/ 0.7 mmol/L) compared with the more evident metabolic acidosis observed in those born to -70 DCAD cows (pH = 7.28 +/- 0.02; pCO2 = 59.3 +/- 2.4 mmHg; HCO3- = 27.8 +/- 0.7 mmol/L). Heifers born to -180 DCAD dams had reduced concentrations of beta-hydroxybutric acid and nonesterified fatty acids compared with those born to -70 DCAD dams. Efficiency of IgG transfer from colostrum into blood and serum concentrations did not differ among treatments. There was no relationship between measures of metabolic acidosis and measures of efficiency of IgG absorption. Percentage of lymphocytes and neutrophils was altered by maternal treatments; however, treatments did not affect calf morbidity. Extending the duration of feeding up to 42 d or reducing the level of negative DCAD to -180 mEq/kg in maternal diets exerted a transient metabolic acidosis in the calves and slightly affected measures of mineral, energy metabolism, and growth. PMID- 28987582 TI - Rheological and sensory performance of a protein-based sweetener (MNEI), sucrose, and aspartame in yogurt. AB - Sweeteners and flavors are generally added to yogurt to make them more palatable. However, the addition of these ingredients may affect the fermentation process of yogurt as well as its physical and sensory characteristics. Consumers prioritize yogurt products that are "natural." A modified single-chain form of the natural sweet protein monellin extracted from the fruit of Dioscoreophyllum cumminsii, called MNEI, could be a useful alternative to artificial sweeteners. The aim of the present work was to evaluate new rapid sensory methods in combination with rheology to assess the viability of using MNEI to develop sweetened yogurts without the calories of sugar. We studied the gelation and cooling kinetics of 4 yogurt samples (unsweetened or sweetened with MNEI, aspartame, or sucrose) by using a rheometer. Furthermore, the 4 yogurts, with and without addition of a flavoring agent, were characterized from a sensory perspective using a combination of 2 rapid sensory methods, ultra flash profile and flash profile. Rheological results showed that, when added at typical usage levels, aspartame, sucrose, and MNEI did not generally affect the yogurt fermentation process or its rheological properties. Sensory results demonstrated that texture attributes of yogurts with aspartame and sucrose were strongly linked to sweetness and flavor perception, but this was not true for MNEI-sweetened yogurts. In contrast to results obtained from samples sweetened with sucrose and aspartame, MNEI protein did not sweeten the yogurt when added before fermentation. This study highlights the enhancing effect of flavor on sweetness perception, supporting previous reports that noted synergistic effects between sucrose or aspartame and flavors. Hence, future studies should be conducted to determine how sweet proteins behave in yogurt when added after fermentation. PMID- 28987583 TI - Physically adjusted neutral detergent fiber system for lactating dairy cow rations. II: Development of feeding recommendations. AB - The objective of this work was to leverage equations derived in a meta-analysis into an ensemble modeling system for estimating dietary physical and chemical characteristics required to maintain desired rumen conditions in lactating dairy cattle. Given the availability of data, responsiveness of ruminal pH to animal behaviors, and the chemical composition and physical form of the diet, mean ruminal pH was chosen as the primary rumen environment indicator. Physically effective fiber (peNDF) is defined as the fraction of neutral detergent fiber (NDF) that stimulates chewing activity and contributes to the floating mat of large particles in the rumen. The peNDF of feedstuffs is typically estimated by multiplying the NDF content by a particle size measure, resulting in an estimated index of effectiveness. We hypothesized that the utility of peNDF could be expanded and improved by dissociating NDF and particle size and considering other dietary factors, all integrated into a physically adjusted fiber system that can be used to estimate minimum particle sizes of TMR and diet compositions needed to maintain ruminal pH targets. Particle size measures of TMR were limited to those found with the Penn State particle separator (PSPS). Starting with specific diet characteristics, the system employed an ensemble of models that were integrated using a variable mixture of experts approach to generate more robust recommendations for the percentage of dietary DM material that should be retained on the 8-mm sieve of a PSPS. Additional continuous variables also integrated in the physically adjusted fiber system include the proportion of material (dry matter basis) retained on the 19- and 8-mm sieves of the PSPS, estimated mean particle size, the dietary concentrations of forage, forage NDF, starch, and NDF, and ruminally degraded starch and NDF. The system was able to predict that the minimum proportion of material (dry matter basis) retained on the 8-mm sieve should increase with decreasing forage NDF or dietary NDF. Additionally, the minimum proportion of dry matter material on the 8-mm sieve should increase with increasing dietary starch. Results of this study agreed with described interrelationships between the chemical and physical form of diets fed to dairy cows and quantified the links between NDF intake, diet particle size, and ruminal pH. Feeding recommendations can be interpolated from tables and figures included in this work. PMID- 28987584 TI - Acid or erythromycin stress significantly improves transformation efficiency through regulating expression of DNA binding proteins in Lactococcus lactis F44. AB - Lactococcus lactis is a gram-positive bacterium used extensively in the dairy industry and food fermentation, and its biological characteristics are usually improved through genetic manipulation. However, poor transformation efficiency was the main restriction factor for the construction of engineered strains. In this study, the transformation efficiency of L. lactis F44 showed a 56.1-fold increase in acid condition (pH 5.0); meanwhile, erythromycin stress (0.04 MUg/mL) promoted the transformation efficiency more significantly (76.9-fold). Notably, the transformation efficiency of F44e (L. lactis F44 harboring empty pLEB124) increased up to 149.1-fold under the synergistic stresses of acid and erythromycin. In addition, the gene expression of some DNA binding proteins (DprA, RadA, RadC, RecA, RecQ, and SsbA) changed correspondingly. Especially for radA, 25.1-fold improvement was detected when F44e was exposed to pH 5.0. Overexpression of some DNA binding proteins could improve the transformation efficiency. The results suggested that acid or erythromycin stress could improve the transformation efficiency of L. lactis through regulating gene expression of DNA binding proteins. We have proposed a simple but promising strategy for improving the transformation efficiency of L. lactis and other hard-transformed microorganisms. PMID- 28987585 TI - Producer estimates of prevalence and perceived importance of lameness in dairy herds with tiestalls, freestalls, and automated milking systems. AB - Lameness is one of the most important welfare and productivity concerns in the dairy industry. Our objectives were to obtain producers' estimates of its prevalence and their perceptions of lameness, and to investigate how producers monitor lameness in tiestall (TS), freestall with milking parlor (FS), and automated milking system (AMS) herds. Forty focal cows per farm in 237 Canadian dairy herds were scored for lameness by trained researchers. On the same day, the producers completed a questionnaire. Mean herd-level prevalence of lameness estimated by producers was 9.0% (+/-0.9%; +/-SE), whereas the researchers observed a mean prevalence of 22.2% (+/-0.9%). Correlation between producer- and researcher-estimated lameness prevalence was low (r = 0.19) and mean researcher prevalence was 1.6, 1.8, and 4.1 times higher in AMS, FS, and TS farms, respectively. A total of 48% of producers thought lameness was a moderate or major problem in their herds (TS = 34%; AMS =53%; FS = 59%). One third of producers considered lameness the highest ranked health problem they were trying to control, whereas two-thirds of producers (TS = 43%; AMS = 63%; FS = 71%) stated that they had made management changes to deal with lameness in the past 2 yr. Almost all producers (98%) stated they routinely check cows to identify new cases of lameness; however, 40% of producers did not keep records of lameness (AMS = 24%; FS = 23%; TS = 60%). A majority (69%) of producers treated lame cows themselves immediately after detection, whereas 13% relied on hoof-trimmer or veterinarians to plan treatment. Producers are aware of lameness as an issue in dairy herds and almost all monitor lameness as part of their daily routine. However, producers underestimate lameness prevalence, which highlights that lameness detection continues to be difficult in in all housing systems, especially in TS herds. Training to improve detection, record keeping, identification of farm-specific risk factors, and treatment planning for lame cows is likely to help decrease lameness prevalence. PMID- 28987586 TI - Comparison of treatment records and inventory of empty drug containers to quantify antimicrobial usage in dairy herds. AB - Assessment of antimicrobial use (AMU) is vital for interpreting the origin of changes in antimicrobial resistance (AMR). The objectives of the present study were to estimate the association between AMU determined using on-farm treatment records (TR) and inventory of empty drug containers (INV). Herds were selected to represent Canadian dairy farms. Producers were asked to record animal health events and treatments on a standard General Health Event form. For inventory data, 40-L receptacles were placed at various locations considered convenient to deposit all empty drug containers. Antimicrobial defined-daily dosages (ADD) were calculated for 51 Canadian herds using the 2 methods. Estimation of AMU was 31,840 ADD using the INV and 14,487 ADD using the TR, indicating that for every TR entry, 2.20 times more treatments were observed using the INV. Mastitis, reproductive conditions, and dry cow therapy were the most frequent reasons for antimicrobial therapy when assessing TR. For all antimicrobials evaluated, mean ADD was higher using the INV versus TR. Regardless, a strong positive correlation (0.80) was observed between the 2 methods, indicating that herds with increased number of ADD recorded using the INV also had increased number of ADD recorded using TR. Furthermore, a positive association was observed for the 6 most commonly used antimicrobials. In comparison to methods used in surveillance programs on AMU in livestock that assume a constant use in all herds (i.e., sales data), INV provided a herd-level specific quantity of AMU positively correlated with AMU recorded at the animal level in general. The INV was easy to implement and provided a measure of total AMU in the herd. Availability of such information would be valuable for interpreting changes in AMR at the herd level and enabling evaluation of interventions for decreasing AMR. PMID- 28987587 TI - Relationship between intramammary infection prevalence and somatic cell score in commercial dairy herds. AB - We examined consistency of the relationship between intramammary infection (IMI) and somatic cell score (SCS) across several classes of cow, herd, and sampling time variables. Microbial cultures of composite milk samples were performed by New York Quality Milk Production Services from 1992 to 2004. SCS was from the most recent Dairy Herd Improvement test before IMI sampling. Records were analyzed from 79,308 cows in 1,124 commercial dairy herds representing a broad range of production systems. Three binary dependent variables were presence or absence of contagious IMI, environmental IMI, and all IMI. Independent variables in the initial models were SCS, SCS2, lactation number, days in milk, sample day milk yield, use of coliform mastitis vaccine, participant type (required by regulation or voluntary), production system (type of housing, milking system, and herd size), season of sampling, year of sampling, and herd; also the initial models included interactions of SCS and SCS2 with other independent variables, except herd and milk yield. Interaction terms characterize differences in the IMI SCS relationship across classes of the independent variables. Models were derived using the Glimmix macro in SAS (SAS Institute Inc., Cary, NC) with a logistic link function and employing backward elimination. The final model for each dependent variable included all significant independent variables and interactions. Simplified models omitted SCS2 and all interactions with SCS. Interactions of SCS with days in milk, use of coliform mastitis vaccine, participant type, season, and year were not significant in any of the models. Interaction of SCS with production system was significant for the all IMI model, whereas interaction of SCS with lactation number was significant for the environmental and all IMI models. Each 1-point increase in SCS (or doubling of somatic cell count) was associated with a 2.3, 5.5, and 9.1% increase in prevalence of contagious, environmental, and all IMI, respectively. Empirical receiver operator characteristic curves and areas under the curve were derived for final and simplified models. The areas under the curve for simplified and final models within each type of IMI differed by 0.009 or less. We concluded that the relationship of IMI with SCS was generally stable over time and consistent across seasons, production systems, and cow factors. PMID- 28987588 TI - Characterization of luteal dynamics in lactating Holstein cows for 32 days after synchronization of ovulation and timed artificial insemination. AB - Approximately 20 to 30% of cows diagnosed not pregnant 32 d after timed artificial insemination (TAI) lack a corpus luteum (CL), and cows submitted to a resynchronization protocol in the absence of a CL have about 10% fewer pregnancies per AI (P/AI) than cows with a CL. An understanding of luteal dynamics after synchronization of ovulation and TAI may help refine strategies for reinseminating cows failing to conceive. Lactating Holstein cows (n = 141) were synchronized for first TAI using a Double-Ovsynch protocol. Thrice weekly from 4 to 32 d after TAI, blood samples were collected for evaluation of plasma progesterone (P4) concentrations, and CL diameter was measured using transrectal ultrasonography. Pregnancy status was determined using transrectal ultrasonography 32 d after TAI. Nonsynchronized cows (n = 4) were removed from the study. For cows diagnosed pregnant 32 d after TAI (n = 57), P4 increased from 4 to 15 d and then remained constant until 32 d after TAI, whereas CL volume increased from 4 to 11 d and then remained constant until 32 d after TAI. For cows diagnosed not pregnant 32 d after TAI (n = 80), P4 profiles were evaluated using statistical cluster analysis based on the day after TAI that P4 decreased to <1 ng/mL, resulting in 5 clusters: (1) CL regression 15 d after TAI (1.3%), (2) CL regression 18 to 22 d after TAI (55.0%), (3) CL regression 25 to 27 d after TAI (17.5%), (4) CL regression 29 to 32 d after TAI (5.0%), and (5) CL maintained until 32 d after TAI (21.3%). Plasma pregnancy-associated glycoprotein (PAG) levels at 25 and 32 d after TAI differed among clusters and were below the cut-off value of the assay for the classification of cows as not pregnant for cows in clusters 2, 3, and 4, whereas more than half of the cows in cluster 5 had increased plasma PAG levels. We conclude that at least half of the nonpregnant cows that maintained their CL until 32 d after TAI were initially pregnant but underwent early pregnancy loss based on increased plasma PAG levels at 25 and 32 d after TAI. PMID- 28987589 TI - Hydroxy-selenomethionine: A novel organic selenium source that improves antioxidant status and selenium concentrations in milk and plasma of mid lactation dairy cows. AB - This study aimed to evaluate the effect of hydroxy-selenomethionine (HMSeBA), a novel organic selenium (Se) source, on milk performance, antioxidative status, and Se concentrations in the milk and plasma of mid-lactation dairy cows compared with that of sodium selenite (SS). Fifty mid-lactation dairy cows with similar days in milk, milk yield, and parity received the same basal diet containing 0.06 mg of Se/kg of DM. They were assigned to 1 of 5 treatments according to a randomized complete block design: negative control (without Se supplementation), SS supplementation (0.3 mg of Se/kg of DM; SS-0.3) or HMSeBA supplementation (0.1, 0.3, or 0.5 mg of Se/kg of DM: SO-0.1, SO-0.3, and SO-0.5, respectively). The experiment lasted for 10 wk, including a pretrial period of 2 wk. The results indicated that neither Se supplementation nor Se source affected dry matter intake, milk yield, milk composition, or blood biochemical parameters, except for milk fat percentage. Simultaneously, milk fat percentage and milk fat yield increased linearly as the quantity of HMSeBA supplementation was increased. Production of 4% FCM and ECM was elevated linearly as dietary HMSeBA increased. The SO-0.3 group showed higher serum activity of glutathione peroxidase, total antioxidant capacity, and superoxide dismutase than the SS-0.3 group, but malondialdehyde content was not affected by Se source. Furthermore, HMSeBA supplementation linearly increased the activities of serum glutathione peroxidase and superoxide dismutase, but decreased malondialdehyde content. Compared with the SS-0.3 group, the SO-0.3 group showed augmented concentrations of total Se in milk and plasma, and total Se milk-to-plasma concentration ratio. In addition, increasing doses of HMSeBA linearly increased the concentrations of total Se in the milk and plasma. This study demonstrates that HMSeBA improves antioxidant status and increases milk and plasma Se concentrations more effectively than SS, indicating that HMSeBA could replace SS as an effective organic Se source for lactating dairy cows. PMID- 28987591 TI - A dynamic model to simulate potassium balance in dairy cows. AB - High-performing dairy cows require a particular composition of nutritional ingredients, adapted to their individual requirements and depending on their production status. The optimal dimensioning of minerals in the diet, one being potassium, is indispensable for the prevention of imbalances. Potassium balance in cows is the result of potassium intake, distribution in the organism, and excretion, and it is closely related to glucose and electrolyte metabolism. In this paper, we present a dynamical model for potassium balance in lactating and nonlactating dairy cows based on ordinary differential equations. Parameter values were obtained from clinical trial data and from the literature. To verify the consistency of the model, we present simulation outcomes for 3 different scenarios: potassium balance in (1) nonlactating cows with varying feed intake, (2) nonlactating cows with varying potassium fraction in the diet, and (3) lactating cows with varying milk production levels. The results give insights into the short- and long-term potassium metabolism, providing an important step toward the understanding of the potassium network, the design of prophylactic feed additives, and possible treatment strategies. PMID- 28987590 TI - Viable Mycobacterium avium ssp. paratuberculosis isolated from calf milk replacer. AB - When advising farmers on how to control Johne's disease in an infected herd, one of the main recommendations is to avoid feeding waste milk to calves and instead feed calf milk replacer (CMR). This advice is based on the assumption that CMR is free of viable Mycobacterium avium ssp. paratuberculosis (MAP) cells, an assumption that has not previously been challenged. We tested commercial CMR products (n = 83) obtained from dairy farms around the United States by the peptide-mediated magnetic separation (PMS)-phage assay, PMS followed by liquid culture (PMS-culture), and direct IS900 quantitative PCR (qPCR). Conventional microbiological analyses for total mesophilic bacterial counts, coliforms, Salmonella, coagulase-negative staphylococci, streptococci, nonhemolytic Corynebacterium spp., and Bacillus spp. were also performed to assess the overall microbiological quality of the CMR. Twenty-six (31.3%) of the 83 CMR samples showed evidence of the presence of MAP. Seventeen (20.5%) tested positive for viable MAP by the PMS-phage assay, with plaque counts ranging from 6 to 1,212 pfu/50 mL of reconstituted CMR (average 248.5 pfu/50 mL). Twelve (14.5%) CMR samples tested positive for viable MAP by PMS-culture; isolates from all 12 of these samples were subsequently confirmed by whole-genome sequencing to be different cattle strains of MAP. Seven (8.4%) CMR samples tested positive for MAP DNA by IS900 qPCR. Four CMR samples tested positive by both PMS-based tests and 5 CMR samples tested positive by IS900 qPCR plus one or other of the PMS-based tests, but only one CMR sample tested positive by all 3 MAP detection tests applied. All conventional microbiology results were within current standards for whole milk powders. A significant association existed between higher total bacterial counts and presence of viable MAP indicated by either of the PMS-based assays. This represents the first published report of the isolation of viable MAP from CMR. Our findings raise concerns about the potential ability of MAP to survive manufacture of dried milk-based products. PMID- 28987592 TI - Cathepsin S inhibition suppresses autoimmune-triggered inflammatory responses in macrophages. AB - In several types of antigen-presenting cells (APCs), Cathepsin S (CatS) plays a crucial role in the regulation of MHC class II surface expression and consequently influences antigen (Ag) presentation of APCs to CD4+ T cells. During the assembly of MHC class II-Ag peptide complexes, CatS cleaves the invariant chain p10 (Lip10) - a fragment of the MHC class II-associated invariant chain peptide. In this report, we used a selective, high-affinity CatS inhibitor to suppress the proteolytic activity of CatS in lymphoid and myeloid cells. CatS inhibition resulted in a concentration-dependent Lip10 accumulation in B cells from both healthy donors and patients with systemic lupus erythematosus (SLE). Furthermore, CatS inhibition led to a decreased MHC class II expression on B cells, monocytes, and proinflammatory macrophages. In SLE patient-derived peripheral blood mononuclear cells, CatS inhibition led to a suppressed secretion of IL-6, TNFalpha, and IL-10. In a second step, we tested the effect of CatS inhibition on macrophages being exposed to patient-derived autoantibodies against C1q (anti-C1q) that are known to be associated with severe lupus nephritis. As shown previously, those SLE patient-derived high-affinity anti-C1q bound to immobilized C1q induce a proinflammatory phenotype in macrophages. Using this human in vitro model of autoimmunity, we found that CatS inhibition reduces the inflammatory responses of macrophages as demonstrated by a decreased secretion of proinflammatory cytokines, the downregulation of MHC class II and CD80. In summary, we can show that the used CatS inhibitor is able to block Lip10 degradation in healthy donor- and SLE patient-derived B cells and inhibits the induction of proinflammatory macrophages. Thus, CatS inhibition seems to be a promising future treatment of SLE. PMID- 28987593 TI - MRGPRX2 is essential for sinomenine hydrochloride induced anaphylactoid reactions. AB - Mast cells are unique immunocytes that function as sentinel cells in host defense reactions such as immediate hypersensitivity responses and anaphylactic responses. The mast cell specific receptor MRGPRX2 (Mas-related G protein-coupled receptor X2) triggers mast cell degranulation-a key process in anaphylactic reactions. We sought to better understand anaphylactic reaction induced by sinomenine hydrochloride (SH). MRGPRX2-related pseudo-allergic reactions induced by SH were investigated using the hindpaw swelling and extravasation assay in vivo and mast cell degranulation assays in vitro. MrgprB2 knockout mice exhibit a reduced SH-induced inflammation effect. Furthermore, MRGPRX2 (the orthologous gene of MrgprB2) related human mast cells are activated by SH in a dose-dependent manner; however, MRGPRX2 knockdown mast cells showed reduced degranulation. The results showed a kind of mechanism that SH-induced anaphylactoid reactions were mediated by MRGPRX2 via activating PLC molecular signaling pathways to provoke mast cells Ca2+ mobilization and degranulation. PMID- 28987594 TI - Auxiliary subunits of AMPA receptors: The discovery of a forebrain-selective antagonist, LY3130481/CERC-611. AB - Drugs originate from the discovery of compounds, natural or synthetic, that bind to proteins (receptors, enzymes, transporters, etc.), the interaction of which modulates biological cascades that have potential therapeutic benefit. Rational strategies for identifying novel drug therapies are typically based on knowledge of the structure of the target proteins and the design of new chemical entities that modulate these proteins in a beneficial manner. The present review discusses a novel approach to drug discovery based on the identification and characterization of auxiliary proteins, the transmembrane AMPA receptor regulatory proteins (TARPs) that are associated with AMPA receptors. Utilizing these auxiliary proteins in compound screening led to the discovery of the TARP dependent-AMPA forebrain selective receptor antagonist (TDAA), LY3130481/CERC-611 that is currently in clinical development for epilepsy. PMID- 28987595 TI - Acylated apelin-13 amide analogues exhibit enzyme resistance and prolonged insulin releasing, glucose lowering and anorexic properties. AB - The adipokine, apelin has many biological functions but its activity is curtailed by rapid plasma degradation. Fatty acid derived apelin analogues represent a new and exciting avenue for the treatment of obesity-diabetes. This study explores four novel fatty acid modified apelin-13 analogues, namely, (Lys8GluPAL)apelin-13 amide, pGlu(Lys8GluPAL)apelin-13 amide, Lys8GluPAL(Tyr13)apelin-13 and Lys8GluPAL(Val13)apelin-13. Fatty acid modification extended the half-life of native apelin-13 to >24 h in vitro. pGlu(Lys8GluPAL)apelin-13 amide was the most potent insulinotropic analogue in BRIN-BD11 cells and isolated islets with maximal stimulatory effects of up to 2.7-fold (p < .001). (Lys8GluPAL)apelin-13 amide (1.9-fold) and Lys8GluPAL(Tyr13)apelin-13 (1.7-fold) were less effective, whereas Lys8GluPAL(Val13)apelin-13 had an inhibitory effect on insulin secretion. Similarly, pGlu(Lys8GluPAL)apelin-13 amide was most potent in increasing beta cell intracellular Ca2+ concentrations (1.8-fold, p < .001) and increasing glucose uptake in 3T3-L1 adipocytes (2.3-fold, p < .01). Persistent biological action was observed with both pGlu(Lys8GluPAL)apelin-13 amide and (Lys8GluPAL)apelin-13 amide significantly reducing blood glucose (39-43%, p < .01) and enhancing insulin secretion (43-56%, p < .001) during glucose tolerance tests in diet-induced obese mice. pGlu(Lys8GluPAL)apelin-13 amide and (Lys8GluPAL)apelin-13 amide also inhibited feeding (28-40%, p < .001), whereas Lys8GluPAL(Val13)apelin-13 increased food intake (8%, p < .05) in mice. These data indicate that novel enzymatically stable analogues of apelin-13 may be suitable for future development as therapeutic agents for obesity-diabetes. PMID- 28987596 TI - Computational discovery and experimental verification of farnesoid X receptor agonist auraptene to protect against cholestatic liver injury. AB - Recently obeticholic acid (OCA) which is a farnesoid X receptor (FXR) agonist was approved by FDA to treat cholestatic liver diseases, which provided us a novel therapeutic strategy against cholestasis. Herein, we used a novel computational strategy with two-dimensional virtual screening for FXR agonists. For the first time, we found that auraptene (AUR), a natural product, can activate FXR to exert hepatoprotective effect against cholestatic liver injury in vivo and in vitro. Importantly, AUR was found to significantly decrease the mortality of cholestatic mice. Dynamic change analysis of bile acids and gene analysis revealed that AUR promoted bile acid efflux from liver into intestine via an induction in FXR target genes Bsep and Mrp2 expression, and reduced hepatic uptake through an inhibition in Ntcp. Furthermore, AUR reduced bile acid synthesis through repressing FXR-target genes Cyp7a1 and Cyp8b1, and increased bile acid metabolism through an induction in Sult2a1. In addition, AUR promoted liver repair through an induction in liver regeneration-related gene, and suppressed liver inflammation through repressing inflammation-related gene NF-kappaB, TNF-alpha, IL-1beta and IL-6. However, the changes in these genes and protein, as well as ameliorative liver histology induced by AUR were abrogated by FXR antagonist guggulsterone in vivo and FXR siRNA in vitro. These findings suggest that AUR may be an effective approach for the prevention against cholestatic liver diseases. PMID- 28987597 TI - Reflection on the selection of doses of arenobufagin in vivo anticancer study. PMID- 28987598 TI - The Brazilian market of herbal medicinal products and the impacts of the new legislation on traditional medicines. AB - ETHNOPHARMACOLOGICAL RELEVANCE: the herbal medicinal products (HMP) market is expanding in the world, an expansion that has not occurred in Brazil when considering the number of licensed products. Despite being a megadiverse country, the number of HMP licensed in Brazil is small, and the number of HMP obtained from native species is even smaller. A new legislation for herbal products licensing, which divides the products into two categories, Herbal Medicine (HM) and Traditional Herbal Product (THP) was launched in Brazil focusing on traditional use, as well as a law regulating the use of biodiversity and traditional knowledge. AIM OF THE STUDY: to evaluate the situation of HMP licensed in Brazil and to make a comparison with the data obtained in 2008 and 2011, discussing the evolution of the licensed products and the possible impacts of the new legislation. MATERIALS AND METHODS: a survey was carried out in the Brazilian Health Regulatory Agency (Anvisa) database to verify the HMP licensed in Brazil in September 2016. The data obtained were compared with two surveys previously published. RESULTS: There are 332 single, and 27 combined HM, totaling 359 HM licensed in Brazil. There is no THP notified in Anvisa's system yet. There are 214 HM classified as nonprescription (OTC), while 145 are sold under prescription, one of them with prescription retention. There are 101 plant species licensed as active in HM in Brazil, 39 of which are native, adapted or cultivated. The most licensed plant species is Mikania glomerata Spreng., with 25 HM licensed. The article includes tables with plant species that have derivatives licensed as simple and combined HM, their therapeutic classification, the native plant species indication and the distribution of the companies by Brazilian regions. CONCLUSIONS: There are few licensed HM in Brazil, and this number has been decreasing in recent years. It is expected that the data obtained, together with the changes promoted in sanitary and environmental rules, will help to develop and regulate HMP chain in Brazil. PMID- 28987599 TI - Anti-sepsis protection of Xuebijing injection is mediated by differential regulation of pro- and anti-inflammatory Th17 and T regulatory cells in a murine model of polymicrobial sepsis. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Xuebijing injection (XBJ), a Chinese herbal medicine containing extracts from 5 herbs, is frequently used as an add-on with standard therapies to treat sepsis or septic shock with fewer side effects in China. Nonetheless, its mechanism of action on septic shock remains to be unveiled. We explored the differential effects of XBJ on subtypes of CD4+ T cell differentiation and septic shock protection in a murine model to understand the contribution of XBJ to regulation of the inflammation-immune axis function. MATERIALS AND METHODS: In vitro T cell differentiation assays were performed to determine the effect of XBJ on CD4+ regulatory T cell and T helper cell differentiation. Besides, 2ml/kg, 6ml/kg- and 18ml/kg of XBJ were administered to different groups of septic mice once/day for 5 days after cecal ligation and puncture (CLP) surgeries. 36h after CLP, serum levels of pro-inflammatory cytokine TNF-alpha and IL-6 were determined with Elisa. Frequencies of CD4+ T cells were analyzed after staining with Tregs and T helper cell lineage specific antibodies by flow cytometer. RESULTS: XBJ at 18ml/kg stimulated Treg differentiation and moderately inhibited Th17 differentiation in vitro. Accordingly, 18ml/kg XBJ facilitated the expansion of IL-10+ Tregs and normalized pro-inflammatory Th17 population in septic mice. This regimen also significantly reduced serum levels of inflammatory cytokines TNF-alpha and IL-6 in septic mice. Additionally, 18ml/kg XBJ injection effectively prevented neutrophil infiltration into the lung and kidney and improved survival in this septic shock model. CONCLUSIONS: In summary, XBJ improves survival in septic shock partially through preventing cytokine storm, inhibiting inflammation and regulating the balance of Tregs and Th17 cells. Thus, higher dose of XBJ is a potential regimen to benefit septic shock patients. PMID- 28987600 TI - Lipid lowering agents of natural origin: An account of some promising chemotypes. AB - The role of natural products in the drug development and discovery has been phenomenal. There has been an enormous interest in exploring all possible natural sources to identify structures exhibiting pronounced hypolipidemic activity albeit with no toxicity. The present review describes the profile of some interesting naturally occurring compounds and their derivatives as potential hypolipidemic agents. Some of the interesting natural chemotypes that can control the increased levels of plasma lipids and discussed in this review are compactin, lovastatin, gugglesterone, berberine, lupeol, phytol, polyprenol, aegeline, 4 hydroxyisoleucine, alpha-asarone, resveratrol, esculeoside A, swertiamarin, rutin, saucerneol B, curcumin and a clerodane diterpene. PMID- 28987601 TI - Design, synthesis and anti-HIV evaluation of novel diarylpyridine derivatives as potent HIV-1 NNRTIs. AB - As a continuation of our efforts to discover and develop "me-better" drugs of DAPYs, novel diarylpyridine derivatives were designed, synthesized and evaluated for their anti-HIV activities in MT-4 cells. The majority of these compounds showed high activity against wild-type HIV-1 strain (IIIB) with EC50 values in the range of 0.04-4.41 MUM. Among them, compound 5b2 (EC50 = 0.04 MUM, SI = 3963) was the most potent. This compound showed anti-HIV-1IIIB activity superior than of Nevirapine but still inferior than of Etravirine. Selected compounds were also evaluated for the activity against reverse transcriptase (RT), and most of the compounds exhibited submicromolar IC50 values indicating they are specific RT inhibitors. Preliminary structure-activity relationships and modeling studies of these new analogues provide valuable avenues for future molecular optimization. PMID- 28987602 TI - Design and synthesis of tranylcypromine derivatives as novel LSD1/HDACs dual inhibitors for cancer treatment. AB - Lysine specific demethylase 1 (LSD1) and Histone deacetylases (HDACs) are promising drug targets for cancers. Recent studies reveal an important functional interplay between LSD1 and HDACs, and there is evidence for the synergistic effect of combined LSD1 and HDAC inhibitors on cancers. Therefore, development of inhibitors targeting both LSD1 and HDACs might be a promising strategy for epigenetic therapy of cancers. We report herein the synthesis of a series of tranylcypromine derivatives as LSD1/HDACs dual inhibitors. Most compounds showed potent LSD1 and HDACs inhibitory activity, especially compound 7 displayed the most potent inhibitory activity against HDAC1 and HDAC2 with IC50 of 15 nM and 23 nM, as well as potent inhibition against LSD1 with IC50 of 1.20 MUM. Compound 7 demonstrated stronger anti-proliferative activities than SAHA with IC50 values ranging from 0.81 to 4.28 MUM against MGC-803, MCF-7, SW-620 and A-549 human cancer cell lines. Further mechanistic studies showed that compound 7 treatment in MGC-803 cells dose-dependently increased cellular H3K4 and H3K9 methylation, as well as H3 acetylation, decreased the mitochondrial membrane potential and induced remarkable apoptosis. Docking studies showed that compound 7 can be well docked into the active binding sites of LSD1 and HDAC2. This finding highlights the potential for the development of LSD1/HDACs dual inhibitors as novel anticancer drugs. PMID- 28987603 TI - Synthesis and antiproliferative properties of new hydrophilic esters of triterpenic acids. AB - To improve the properties of cytotoxic triterpenoid acids 1-5, a large set of hydrophilic esters was synthesized. We choose betulinic acid (1), dihydrobetulinic acid (2), 21-oxoacid 3 along with highly active des-E lupane acids 4 and 5 as a model set of compounds for esterification of which the properties needed to be improved. As ester moieties were used - methoxyethanol and 2-(2-methoxyethoxy)ethanol and glycolic unit (type a-d), pyrrolidinoethanol, piperidinoethanol and morpholinoethanol (type f-h), and monosaccharide groups (type i-l). As a result, 56 triterpenic esters (49 new compounds) were obtained and their cytotoxicity on four cancer cell lines and normal human fibroblasts was tested. All new compounds were fully soluble at all tested concentrations, which used to be a problem of the parent compounds 1 and 2. 16 compounds had IC50 < 10 MUM on at least one cancer cell line, 12 compounds had cytotoxicity of <10 MUM against at least three of four tested cancer cell lines. The highest activity was found for compound 3c (1.8 MUM on MCF7, 2.8 MUM on HeLa, and 1.6 MUM on G-361 cells) which also had no toxicity on non-cancerous BJ fibroblasts at the highest tested concentration (50 MUM). High selective cytotoxicity was also found in compounds 1k, 2k, 3c, and 3i that are ideal candidates for drug development. Therefore, more studies to identify the mechanism of action were performed in case of 1k, 3c, and 3g such as effects on cell cycle and apoptosis. It was found that compounds 3c and 3g can induce apoptosis via caspase-3 activation and modulation of protein Bcl-2 in G-361 cells. In conclusion, compounds 1k, 3c, and 3g show high and selective cytotoxicity, therefore they are significantly better candidates for anti-cancer drug development than the parent acids 1-5. PMID- 28987604 TI - Discovery and synthesis of novel Wogonin derivatives with potent antitumor activity in vitro. AB - Phenotypic screening of high quality compound library is one of the most effective strategy to obtain novel bioactive compounds. Recently, our group have constructed a Wogonin-scaffold library with substituents diversity and successfully obtained a series of potent compounds. Herein, we reported the synthesis of these compounds and evaluated the in vitro antitumor activity against a panel of human tumor cell lines. Most of them showed good activity with a broad spectrum and preliminary structure-activity relationship for the substitutions were obtained. Further biological assays showed that the most potent compounds 18n and 20b could significantly enhance the intracellular ROS level and induce the cell apoptosis at low micromole level. Through similarity searching, CDK9 was identified as the potential target for 20b, which could be a start point for next structure-based drug design. PMID- 28987605 TI - Synthesis of naphthazarin derivatives and identification of novel thioredoxin reductase inhibitor as potential anticancer agent. AB - Mammalian thioredoxin reductase (TrxR) enzymes play a crucial role in regulating multiple redox-based signaling pathways and have attracted increasing attention as promising anticancer drug targets. We report here the synthesis of a panel of naphthazarin derivatives and discovery of 2-methyl-5,8-dihydroxy-1,4 naphthoquinone (3, 2-methylnaphthazarin) as a potent cytotoxic agent with a submicromolar half maximal inhibitory concentration to the human promyelocytic leukemia HL-60 cells. Mechanism studies reveal that the compound selectively inhibits TrxR to induce oxidative stress-mediated apoptosis of HL-60 cells. Knockdown of TrxR sensitizes the cells to 3 insults, while overexpression of the functional enzyme confers resistance to the compound treatment, underpinning the physiological significance of targeting TrxR by 3. Clarification of the interaction of compound 3 with TrxR unveils a mechanism underlying the cellular action of the compound, and sheds light in considering development of the compound as a potential cancer chemotherapeutic agent. PMID- 28987606 TI - Design, synthesis and biological evaluation of 4,7,12,12a-tetrahydro-5H thieno[3',2':3,4]pyrido[1,2-b]isoquinolines as novel adenosine 5'-monophosphate activated protein kinase (AMPK) indirect activators for the treatment of type 2 diabetes. AB - A series of novel berberine derivatives, 4,7,12,12a-tetrahydro-5H thieno[3',2':3,4]pyrido[1,2-b]isoquinolines was designed, synthesized, and biologically evaluated for their anti-diabetic activity. Following the evaluation in two types of cells, compounds 4aa, 4bq, and 4bv stimulated glucose consumption (1.8- to 2.3-fold), reduced gluconeogenesis (60-85%), inhibited mitochondria respiratory chain complex I and activated AMPK indirectly. In a db/db mice model, compounds 4bq and 4bv lowered fasting blood glucose at a dose of 120 mg/kg/day. In addition, compounds 4bq and 4bv were found to possess improved pharmacokinetic profiles (bioavailability 45 and 106%, respectively) compared to berberine. Compounds 4bq and 4bv exhibited no obvious hERG inhibition (IC50 > 10 MUM). PMID- 28987607 TI - 2-Aminothiophene scaffolds: Diverse biological and pharmacological attributes in medicinal chemistry. AB - 2-Aminothiophenes are important five-membered heterocyclic building blocks in organic synthesis, and the chemistry of these small molecules is still developing based on the discovery of cyclization by Gewald. Another attractive feature of 2 aminothiophene scaffolds is their ability to act as synthons for the synthesis of biological active thiophene-containing heterocycles, conjugates and hybrids. Currently, the biological actions of 2-aminothiophenes or their 2-N-substituted analogues are still being investigated because of their various mechanisms of action (e.g., pharmacophore and pharmacokinetic properties). Likewise, the 2 aminothiophene family is used as diverse promising selective inhibitors, receptors, and modulators in medicinal chemistry, and these compounds even exhibit effective pharmacological properties in the various clinical phases of appropriate diseases. In this review, major biological and pharmacological reports on 2-aminothiophenes and related compounds have been highlighted; most perspective drug-candidate hits were selected for discussion and described, along with additional synthetic pathways. In addition, we focused on the literature dedicated to 2-aminothiophenes and 2-N-substituted derivatives, which have been published from 2010 to 2017. PMID- 28987608 TI - Spirotriazoline oxindoles: A novel chemical scaffold with in vitro anticancer properties. AB - The design and synthesis of a library of twenty-six spirotriazoline oxindoles and their in vitro evaluation as potential anticancer agents is reported. The antiproliferative activity of the synthesized compounds was assessed against four different cancer cell lines (HCT-116 p53(+/+), HCT-116 p53(-/-), MCF-7, and MDA MB-231). Four spirotriazoline oxindoles showed selectivity against the four cancer cell lines tested over the non-cancer derived HEK 293T cell line. To characterize the molecular mechanisms involved in compound antitumoral activity, two spirotriazoline oxindoles were selected for further studies. Both compounds were able to induce apoptosis and cell cycle arrest at G0/G1 phase and upregulated p53 steady-state levels, while decreasing its main inhibitor MDM2, in HCT-116 cells. Importantly, cytotoxic effects induced by spirotriazoline oxindoles occurred in cancer cells without eliciting cell death in non-malignant CCD-18Co human colon fibroblasts. In addition, four spirotriazoline oxindoles showed selectivity against the triple-negative breast cancer cell line MDA-MB-231 with IC50 values of 3.5-6.7 MUM. These results highlight the anticancer potential of spirotriazoline oxindoles, especially when dealing with aggressive and challenging triple-negative breast cancer. PMID- 28987609 TI - Structure-based design and synthesis of 2,4-diaminopyrimidines as EGFR L858R/T790M selective inhibitors for NSCLC. AB - Mutated epidermal growth factor receptor (EGFR) is a major driver of non-small cell lung cancer (NSCLC). The EGFRT790M secondary mutation has become a leading cause of clinically-acquired resistance to gefitinib and erlotinib. Herein, we present a structure-based design approach to increase the potency and selectivity of the previously reported reversible EGFR inhibitor 7, at the kinase and cellular levels. Three-step structure-activity relationship exploration led to promising compounds 19e and 19h with unique chemical structure and binding mode from the other third-generation tyrosine kinase inhibitors. In a human NSCLC xenograft model, 19e and 19h exhibited dose-dependent tumor growth suppression without toxicity. These selective inhibitors are promising drug candidates for EGFRT790M-driven NSCLC. PMID- 28987610 TI - Heterocyclic pharmacochemistry of new rhinovirus antiviral agents: A combined computational and experimental study. AB - Rhinovirus (RV), member of the Enterovirus genus, is known to be involved in more than half of the common colds. Through advances in molecular biology, rhinoviruses have also been associated with exacerbations of chronic pulmonary diseases (e.g. asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis). In the current investigation, we develop a novel series of 4,5 dimethoxybenzyl derivatives that potently inhibits rhinovirus replication. Compound (S)-7f blocks RV-B14 replication with an EC50 value of 0.25 MUM and shows a low toxicity in HeLa cells (CC50 > 271 MUM). Enantioseparation followed by an absolute configuration determination by a Mosher's method revealed the interest of enantiopure compounds. Molecular docking studies permitted the identification of key biological interactions within the drug-binding pocket and an in silico drug-like study revealed a good potential for the development of these derivatives. PMID- 28987611 TI - 5-Ene-4-thiazolidinones - An efficient tool in medicinal chemistry. AB - The presented review is an attempt to summarize a huge volume of data on 5-ene-4 thiazolidinones being a widely studied class of small molecules used in modern organic and medicinal chemistry. The manuscript covers approaches to the synthesis of 5-ene-4-thiazolidinone derivatives: modification of the C5 position of the basic core; synthesis of the target compounds in the one-pot or multistage reactions or transformation of other related heterocycles. The most prominent pharmacological profiles of 5-ene derivatives of different 4-thiazolidinone subtypes belonging to hit-, lead-compounds, drug-candidates and drugs as well as the most studied targets have been discussed. Currently target compounds (especially 5-en-rhodanines) are assigned as frequent hitters or pan-assay interference compounds (PAINS) within high-throughput screening campaigns. Nevertheless, the crucial impact of the presence/nature of C5 substituent (namely 5-ene) on the pharmacological effects of 5-ene-4-thiazolidinones was confirmed by the numerous listed findings from the original articles. The main directions for active 5-ene-4-thiazolidinones optimization have been shown: i) complication of the fragment in the C5 position; ii) introduction of the substituents in the N3 position (especially fragments with carboxylic group or its derivatives); iii) annealing in complex heterocyclic systems; iv) combination with other pharmacologically attractive fragments within hybrid pharmacophore approach. Moreover, the utilization of 5-ene-4-thiazolidinones in the synthesis of complex compounds with potent pharmacological application is described. The chemical transformations cover mainly the reactions which involve the exocyclic double bond in C5 position of the main core and correspond to the abovementioned direction of the 5-ene-4-thiazolidinone modification. PMID- 28987612 TI - A vibrotactile wristband to help older pedestrians make safer street-crossing decisions. AB - INTRODUCTION: Older pedestrians are overrepresented in fatal accidents. Studies consistently show gap-acceptance difficulties, especially in complex traffic situations such as two-way streets and when vehicles approached rapidly. In this context, the present research was aimed at assessing the effectiveness of a vibrotactile device and study older pedestrian's behavior when wearing the wristband designed to help them make safer street-crossing decisions. METHOD: Twenty younger-old participants (age 60-69), 20 older-old participants (age 70 80) and 17 younger adults (age 20-45) carried out a street-crossing task in a simulated two-way traffic environment with and without a vibrotactile wristband delivering warning messages. RESULTS: The percentage of decisions that led to collisions with approaching cars decreased significantly when participants wore the wristband. Benefits tended to be greater particularly among very old women, with fewer collisions in the far lane and when vehicles approached rapidly when they wore the wristband. But collisions did not fall to zero, and responses that were in accordance with the wristband advice went up to only 51.6% on average, for all participants. The wristband was nevertheless considered useful and easy to use by all participants. Moreover, behavioral intentions to buy and use such a device in the future were greater in both groups of older participants, but not among the younger adults. PRACTICAL APPLICATIONS: This haptic device was able to partly compensate for some age-related gap-acceptance difficulties and reduce street-crossing risks for all users. These findings could be fruitfully applied to the design of devices allowing communication between vehicles, infrastructures, and pedestrians. PMID- 28987613 TI - Treatment of cystoid macular edema secondary to retinitis pigmentosa: a systematic review. AB - There are various treatments for cystoid macular edema (CME) secondary to retinitis pigmentosa; however, the evidence for these treatments has not been previously systematically reviewed. Our review that includes 23 studies shows that oral carbonic anhydrase inhibitors (including acetazolamide and methazolamide) and topical carbonic anhydrase inhibitors (dorzolamide and brinzolamide) are effective first-line treatments. In patients unresponsive to carbonic anhydrase inhibitor treatment, intravitreal steroids (triamcinolone acetonide and sustained-release dexamethasone implants), oral corticosteroid (deflazacort), intravitreal antivascular endothelial growth factor agents (ranibizumab and bevacizumab), grid laser photocoagulation, pars plana vitrectomy, or ketorolac were also effective in improving CME secondary to retinitis pigmentosa. Oral acetazolamide has the strongest clinical basis for treatment and was superior to topical dorzolamide. Rebound of CME was commonly seen in the long term, regardless of the choice of treatment. Oral acetazolamide should be the first-line treatment in CME secondary to retinitis pigmentosa. Topical dorzolamide is an appropriate alternative in patients intolerant to adverse effects of oral acetazolamide. More studies are required to investigate the management of rebound CME. PMID- 28987614 TI - Restorative retinal laser therapy: Present state and future directions. AB - Because of complications and side effects, conventional laser therapy has taken a back seat to drugs in the treatment of macular diseases. Despite this, research on new laser modalities remains active. In particular, various approaches are being pursued to preserve and improve retinal structure and function. These include micropulsing, various exposure titration algorithms, and real-time temperature feedback control of short-pulse continuous wave lasers, and ultra short-pulse nanosecond lasers. Some of these approaches are at the preclinical stage of development, whereas others are available for clinical use. Cell biology is providing important insights into the mechanisms of action of retinal laser treatment. We outline the technological bases of current laser platforms, their basic science, therapeutic concepts, clinical experience, and future directions for retinal laser treatment. PMID- 28987615 TI - Improving the quality of depression and pain care in multiple sclerosis using collaborative care: The MS-care trial protocol. AB - BACKGROUND AND OBJECTIVES: Evidence-based pharmacological and behavioral interventions are often underutilized or inaccessible to persons with multiple sclerosis (MS) who have chronic pain and/or depression. Collaborative care is an evidence-based patient-centered, integrated, system-level approach to improving the quality and outcomes of depression care. We describe the development of and randomized controlled trial testing a novel intervention, MS Care, which uses a collaborative care model to improve the care of depression and chronic pain in a MS specialty care setting. METHODS: We describe a 16-week randomized controlled trial comparing the MS Care collaborative care intervention to usual care in an outpatient MS specialty center. Eligible participants with chronic pain of at least moderate intensity (>=3/10) and/or major depressive disorder are randomly assigned to MS Care or usual care. MS Care utilizes a care manager to implement and coordinate guideline-based medical and behavioral treatments with the patient, clinic providers, and pain/depression treatment experts. We will compare outcomes at post-treatment and 6-month follow up. PROJECTED PATIENT OUTCOMES: We hypothesize that participants randomly assigned to MS Care will demonstrate significantly greater control of both pain and depression at post-treatment (primary endpoint) relative to those assigned to usual care. Secondary analyses will examine quality of care, patient satisfaction, adherence to MS care, and quality of life. Study findings will aid patients, clinicians, healthcare system leaders, and policy makers in making decisions about effective care for pain and depression in MS healthcare systems. (PCORI- IH-1304-6379; clinicaltrials.gov: NCT02137044). This trial is registered at ClinicalTrials.gov, protocol NCT02137044. PMID- 28987616 TI - Directional hippocampal-prefrontal interactions during working memory. AB - Working memory refers to a system that is essential for performing complex cognitive tasks such as reasoning, comprehension and learning. Evidence shows that hippocampus (HPC) and prefrontal cortex (PFC) play important roles in working memory. The HPC-PFC interaction via theta-band oscillatory synchronization is critical for successful execution of working memory. However, whether one brain region is leading or lagging relative to another is still unclear. Therefore, in the present study, we simultaneously recorded local field potentials (LFPs) from rat ventral hippocampus (vHPC) and medial prefrontal cortex (mPFC) and while the rats performed a Y-maze working memory task. We then applied instantaneous amplitudes cross-correlation method to calculate the time lag between PFC and vHPC to explore the functional dynamics of the HPC-PFC interaction. Our results showed a strong lead from vHPC to mPFC preceded an animal's correct choice during the working memory task. These findings suggest the vHPC-leading interaction contributes to the successful execution of working memory. PMID- 28987617 TI - Mitigation of postnatal ethanol-induced neuroinflammation ameliorates trace fear memory deficits in juvenile rats. AB - Impairments in behavior and cognition are common in individuals diagnosed with fetal alcohol spectrum disorders (FASD). In this study, FASD model rats were intragastrically intubated with ethanol (5g/kg/day; 5E), sham-intubated (SI), or maintained as naive controls (NC) over postnatal days (PD) 4-9. Ethanol exposure during this human third trimester-equivalent period induces persistent impairments in hippocampus-dependent learning and memory. The ability of ibuprofen (IBU), a non-steroidal anti-inflammatory drug, to diminish ethanol induced neuroinflammation and rescue deficits in hippocampus-dependent trace fear conditioning (TFC) was investigated in 5E rats. Phosphate buffered saline vehicle (VEH) or IBU was injected 2h following ethanol exposure over PD4-9, followed by quantification of inflammation-related genes in the dorsal hippocampus of PD10 rats. The 5E-VEH rats exhibited significant increases in Il1b and Tnf, but not Itgam or Gfap, relative to NC, SI-VEH, and 5E-IBU rats. In separate groups of PD31-33 rats, conditioned fear (freezing) was significantly reduced in 5E-VEH rats during TFC testing, but not acquisition, compared to SI-VEH and, critically, 5E-IBU rats. Results suggest neuroimmune activation in response to ethanol within the neonate hippocampus contributes to later-life cognitive dysfunction. PMID- 28987618 TI - Involvement of cannabinoid system in the nucleus accumbens on delay-based decision making in the rat. AB - The nucleus accumbens (NAc) plays a fundamental role in decision making and anticipation of reward. In addition, exogenous cannabinoids affect the behavior of humans and animals including disruption of short-term memory and cognitive impairments. Therefore, in this study, cannabinoid agonist and antagonist were administrated into the NAc to determine the effect of cannabinoid activation in the entire NAc on delay-based decision making. Rats were trained on a cost benefit T-maze decision making task in which the animals were well-trained to choose between a small/immediate reward and a large/delay reward. After training, the animals were implanted with guide cannulae in the NAc. On test day, they received cannabinoid agonist (Win 55,212-2; 10, 50 and 100MUM) and/or antagonist (AM251; 45MUM) into the NAc. Percentage of high reward choice and latency of reward achievement were evaluated. Results showed that cannabinoid agonist administration caused a decrease in high reward choice such that rats selected small/immediate reward instead of large/delay reward. Moreover, in agonist treated animals latency of reward achievement increased. Effects of cannabinoid activation on delay-based decision making with equivalent delays demonstrated that if the delay was equated on both arm goals, animals still had a preference for the high/delay reward, showing the results was not caused by an impairment of spatial preference or memory. These finding clarified that cannabinoid system activation in the entire NAc plays a critical role in the regulation of delay based decision making. PMID- 28987619 TI - Genetic diversity, phylogroup distribution and virulence gene profile of pks positive Escherichia coli colonizing human intestinal polyps. AB - Some Escherichia coli strains of phylogroup B2 harbor a (pks) pathogenicity island that encodes a polyketide-peptide genotoxin called colibactin. It causes DNA double-strand breaks and megalocytosis in eukaryotic cells and it may contribute to cancer development. Study of bacterial community that colonizes the adenomatous polyp lesion, defined as precancerous lesions, could be helpful to assess if such pathogenic bacteria possess a role in the polyp progression to cancer. In this cross-sectional study, a total of 1500 E. coli isolates were obtained from biopsies of patients presenting adenomatous colon polyps, the normal tissues adjacent to the polyp lesion and patients presenting normal mucosa. pks island frequency, phylogenetic grouping, fingerprint genotyping, and virulence gene features of pks positive (pks+) E. coli isolates were performed. We found pks+E. coli strongly colonize two patients presenting polypoid lesions and none were identified in patients presenting normal mucosa. Predominant phylogroups among pks+E. coli isolates were B2, followed by D. Clustering based on fragment profiles of composite analysis, typed the pks+ isolates into 5 major clusters (I-V) and 17 sub-clusters, demonstrating a high level of genetic diversity among them. The most prevalent virulence genes were fimH and fyuA (100%), followed by vat (92%), hra and papA (69%), ibeA (28%), and hlyA (25%). Our results revealed that pks+E. coli can colonize the precancerous lesions, with a high distribution in both the polyp lesions and in normal tissues adjacent to the lesion. The high differences in fingerprinting patterns obtained indicate that pks+E. coli strains were genetically diverse, possibly allowing them to more easily adapt to environmental variations. PMID- 28987620 TI - Evaluation of culture conditions for mixed biofilm formation with clinically isolated non-albicans Candida species and Staphylococcus epidermidis on silicone. AB - Silicone is frequently used in clinical and medical fields for medical devices. Mixed biofilms composed of Candida and bacterial species causes frequently failure of medical silicone devices, In this in vitro study, we analyzed mixed biofilm formation of clinically isolated non-albicans Candida species and Staphylococcus epidermidis, including Candida tropicalis, Candida krusei and Candida parapsilosis under the influence of different growth media (RPMI 1640, BHI and TSB) and several culture variables (incubation period, feeding conditions and FBS). Our results showed that culture conditions strongly influence mixed biofilm formation. TSB and BHI resulted in larger amount of biofilm formations with stronger metabolic activity of biofilms. Growth conditions may also influence the biofilm formation, which was enhanced by longer incubation period, using a fed-batch system and FBS. Therefore, the potential influences of external environmental factors are very important for mixed biofilm formation with clinically isolated non-albicans Candida species and S. epidermidis, which should be considered when designing or studying the mixed biofilm under in vitro conditions. PMID- 28987621 TI - Combined intervention of static magnetic field and growth rate of Microbacterium maritypicum CB7 for Benzo(a)Pyrene biodegradation. AB - In this work, we have shown for the first time that Microbacterium maritypicum CB7 bacterium is capable to use Benzo(a)Pyrene as a sole source of carbon and energy. We followed the growth kinetics of M. maritypicum CB7 in minimum medium supplemented with 10 mg/l Benzo(a)Pyrene for 30 days. The results obtained showed that M. maritypicum CB7 strain is able to degrade 69% of the initial amount of BaP. In order to improve the rate of biodegradation, we tested for 5 days the effect of a static magnetic field (SMF) at different inductions (50, 100 and 200 mT) on the degradation kinetics of Benzo(a)Pyrene by M. maritypicum CB7. Indeed, at 200 mT, we observed an increase of the yield by the twice of Benzo(a)Pyrene biodegradation rate compared to the non-induced sample. This study shows the important potential of M. maritypicum CB7 for the bioremediation of Benzo(a)Pyrene in the environment and the importance of the application of a SMF to yield the performance of the process suggesting its potential application in bioremediation of polluted sites with hydrocarbons compounds. PMID- 28987622 TI - Immune responses in the haemolymph and antimicrobial peptide expression in the abdomen of Apis mellifera challenged with Spiroplasma melliferum CH-1. AB - Spiroplasma melliferum generally parasitizes honeybees and is one of main pathogens causing 'bee creeping disease' in China. Spiroplasma melliferum can be spread through honeybee pollination, which causes severe economic losses to apiculture. The design of this study was based on previous studies that utilized an in vitro bioassay to investigate the effects of S. melliferum CH-1 infection. We identified invasive S. melliferum CH-1 within Apis mellifera using transmission electron microscopy and investigated the immune response of honeybees infected with S. melliferum CH-1 by assaying the cellular immune response of the haemocytes, the plasma level of phenoloxidase activity and the transcript levels of 5 antimicrobial peptides, including the Abaecin, Apidaecin, Defensin 1, Defensin 2, and Hymenoptaecin gene products. The percentage of granulocytes in the haemolymph of infected honeybees was significantly higher than those of the controls during the early phase of infection, but the percentage of plasmatocytes was significantly higher than those of the controls at the fifth day post-infection. The phenoloxidase activity of the infected honeybees reached a maximum at the second day, and then decreased continuously. Moreover, the transcript levels of the 5 evaluated antimicrobial peptide genes were significantly increased during the early phase of infection and all 5 antimicrobial peptides were significantly decreased during the middle phase of infection. During the late phase of infection, only Defensin 2 and Hymenoptaecin showed significantly increased transcription. These results suggest that the honeybee immune responses could be activated by S. melliferum CH-1 during the early phase of infection and that S. melliferum CH-1 is also capable of circumventing the host defensive mechanisms to complete its life cycle within the honeybee during the middle phase of infection. PMID- 28987623 TI - The pathogenicity and biological features of Santee-Cooper Ranaviruses isolated from Chinese perch and snakehead fish. AB - Ranavirus has become a noticeable threat to both farmed and natural populations of fish and amphibians. Herein, we reported that 3 strains of novel viruses, designated as ScRIV-GM-20150902, CmRIV-XT-20150917 and ScRIV-ZS-20151201, were isolated from diseased Chinese perch and snakehead fish in China. Efficient propagation of these isolates were determined in Chinese perch brain (CPB) cell line by the means of cytopathic effect observation, PCR amplification and electron microscopy observation. And their viral titers in CPB cells reached 108.13 TCID50 ml-1, 107.71 TCID50 ml-1 and 107.94 TCID50 ml-1, respectively. While the challenge experiment results showed that 3 isolates resulted in 100% mortality of Chinese perch after virus infection. Electron microscopy analysis showed that two kinds of viral inclusion bodies (intracytoplasmic and intranuclear inclusion body) were observed in infected CPB cells. Sequence alignment and phylogenetic analysis of major capsid protein gene sequences of isolates revealed that these isolates belonged to the species Santee-Cooper Ranavirus. PMID- 28987624 TI - Toll like receptor 4 signaling pathway participated in Salmonella lipopolysaccharide-induced spleen injury in young chicks. AB - Spleen is one of the crucial sites for cellular and humoral immunity but it easily damaged during pathogenic infections resulting in immunosuppression. The current study was therefore performed to explore the mechanism of acute spleen injury induced by salmonella lipopolysaccharide (LPS) in young chicks. Healthy one-day-old Cobb strain broiler chicks were intra-peritoneally injected with saline or LPS. LPS treatment caused significant decreases in body and spleen weights at 36 and 72 h. Histological analysis showed the changes of ellipsoid structures with beginning of nuclear pyknosis and karyolysis similar to steatosis at 12 h, maximum histopathological lesions were seen at 36 h, however these were disappeared at 72 h post LPS stimulation. Cell proliferation was decreased (low PCNA positivity) and apoptosis increased (high ssDNA positivity) in the spleen at 12 and 36 h after LPS treatment. The expression levels of mRNA for caspase-3, caspase-8, B-cell lymphoma 2 (BCL-2), tumor protein p53 or p53 and Bcl-2 homologous antagonist killer (BAK) showed slight increase at some time points following LPS stimulation. LPS treatment also induced significant up-regulation in toll like receptor 4 (TLR4) at 36 h post LPS stimulation and slight increase in expressions of its downstream molecules (MyD88 and NF-kappaB) at 12 h post LPS treatment. The keystone cytokines (TNF-alpha and IL-6) exhibited significant up regulation at 12 h following LPS stimulation. Our findings provided novel information about the histopathological as well as apoptotic and proliferative alterations in spleen mediated by TLR4 signaling induced by Salmonella LPS in avian species. PMID- 28987625 TI - Effect of toothpaste containing arginine on dental plaque-A randomized controlled in situ study. AB - OBJECTIVES: To evaluate the effects of 8% arginine-containing toothpaste on the dental plaque of no caries (NC) and high caries (HC) individuals in situ. METHODS: 6 no caries (DMFT=0) and 6 high caries (DMFT>=6) individuals wearing a self-developed in situ dental plaque acquisition device were involved in a randomized double-blinded crossover study for 6 weeks: including lead-in (1 week), arginine-free (2 weeks), washout (1 week) and arginine-active (2 weeks) stages. The in situ plaque samples were collected at the endpoint of arginine free and arginine-active stages and subjected to lactic acid production, metabolic activity, live/dead bacteria ratio and total biofilm biomass detections. RESULTS: The arginine-containing dentifrice reduced lactic acid production significantly in both the NC and HC groups, while the inhibitory abilities in the HC group were stronger than that in the NC group. In addition, the arginine-containing dentifrice didn't significantly decrease the metabolic activity, live/dead bacteria ratio and total biofilm biomass in either the NC or the HC group. CONCLUSIONS: Arginine-containing toothpaste can significantly reduce the lactic acid production from the in situ plaques to a low level without changing the metabolic activity, live/dead bacteria ratio and total biofilm biomass through a critical clinical randomized double-blinded crossover study. CLINICAL SIGNIFICANCE: Arginine is a potential ecological prevention and control agent for dental caries. Meanwhile, the in situ model is an easy and pragmatic way to evaluate oral hygiene products (clinical trial registration: ChiCTR-INR 16010226). PMID- 28987626 TI - NO involvement in the inhibition of ghrelin on voltage-dependent potassium currents in rat hippocampal cells. AB - Ghrelin is a peptide hormone that plays an important role in promoting appetite, regulating distribution and rate of use of energy, cognition, and mood disorders, but the relevant neural mechanisms of these function are still not clear. In this study, we examined the effect of ghrelin on voltage-dependent potassium (K+) currents in hippocampal cells of 1-3 days SD rats by whole-cell patch-clamp technique, and discussed whether NO was involved in this process. The results showed that ghrelin significantly inhibited the voltage-dependent K+ currents in hippocampal cells, and the inhibitory effect was more significant when l-arginine was co-administered. In contrast, N-nitro- l-arginine methyl ester increased the ghrelin inhibited K+ currents and attenuated the inhibitory effect of ghrelin. While d-arginine (D-AA) showed no significant impact on the ghrelin-induced decrease in K+ current. These results show that ghrelin may play a physiological role by inhibiting hippocampal voltage dependent K+ currents, and the NO pathway may be involved in this process. PMID- 28987627 TI - Commentary: Fisher's infinitesimal model: A story for the ages. AB - Mendel (1866) suggested that if many heritable "factors" contribute to a trait, near-continuous variation could result. Fisher (1918) clarified the connection between Mendelian inheritance and continuous trait variation by assuming many loci, each with small effect, and by informally invoking the central limit theorem. Barton et al. (2017) rigorously analyze the approach to a multivariate Gaussian distribution of the genetic effects for descendants of parents who may be related. This commentary distinguishes three nested approximations, referred to as "infinitesimal genetics," "Gaussian descendants" and "Gaussian population," each plausibly called "the infinitesimal model." The first and most basic is Fisher's "infinitesimal" approximation of the underlying genetics - namely, many loci, each making a small contribution to the total variance. As Barton et al. (2017) show, in the limit as the number of loci increases (with enough additivity), the distribution of genotypic values for descendants approaches a multivariate Gaussian, whose variance-covariance structure depends only on the relatedness, not the phenotypes, of the parents (or whether their population experiences selection or other processes such as mutation and migration). Barton et al. (2017) call this rigorously defensible "Gaussian descendants" approximation "the infinitesimal model." However, it is widely assumed that Fisher's genetic assumptions yield another Gaussian approximation, in which the distribution of breeding values in a population follows a Gaussian - even if the population is subject to non-Gaussian selection. This third "Gaussian population" approximation, is also described as the "infinitesimal model." Unlike the "Gaussian descendants" approximation, this third approximation cannot be rigorously justified, except in a weak-selection limit, even for a purely additive model. Nevertheless, it underlies the two most widely used descriptions of selection-induced changes in trait means and genetic variances, the "breeder's equation" and the "Bulmer effect." Future generations may understand why the "infinitesimal model" provides such useful approximations in the face of epistasis, linkage, linkage disequilibrium and strong selection. PMID- 28987629 TI - Using binding competitors of albumin to promote the removal of protein-bound uremic toxins in hemodialysis: Hope or pipe dream? AB - Chronic kidney disease is associated with the accumulation of a large range of uremic retention solutes as referred to as uremic toxins. Some of these compounds belong to the group of Protein Bound Uremic Toxins (PBUT) due to their tight interactions with plasma proteins and especially serum albumin. These PBUT therefore exist in the bloodstream into two forms: a major bound (and non diffusible) fraction and a minor free fraction. As a result, these compounds are poorly removed by most of the renal replacement therapies (such as hemodialysis) and their concentration can hardly be decreased in end-stage renal disease patients. An increase of the free fraction of PBUT could be achieved using chemical displacers that could compete with PBUT for binding to serum albumin. This review summarizes and discusses the interest of chemicals displacers as a valuable option to enhance PBUT removal in CKD patients. PMID- 28987628 TI - Nutrient regulation of pancreatic beta-cell proliferation. AB - Excess consumption of energy-dense foods combined with a sedentary lifestyle is driving an obesity epidemic. Although obesity is closely associated with insulin resistance, most individuals meet the insulin demand by increasing their functional beta-cell mass. Those who eventually develop type 2 diabetes are distinguished by a failure in this compensatory process. Although a causal role of insulin resistance in compensatory beta-cell responses has received considerable experimental support, precisely how the beta cell senses changes in the metabolic environment is still unknown. As metabolism of glucose, lipids and amino acids is profoundly altered in obesity, it is not surprising that these nutrients are conspicuous among the factors proposed to contribute. In this review we summarise our understanding of the role of nutrients, in particular glucose, fatty acids and amino acids in beta-cell compensation with a particular emphasis on their relation to insulin resistance-induced factors and their underlying mechanism of action. Finally, we describe the concept of epigenetic programming and review recent studies illustrating how the status of the beta cell epigenome is a product of its nutrient environment, and how metabolic programming of the beta cell contributes to diabetes risk. PMID- 28987630 TI - MRI Texture Analysis Reflects Histopathology Parameters in Thyroid Cancer - A First Preliminary Study. AB - OBJECT: Thyroid cancer represents the most frequent malignancy of the endocrine system with an increasing incidence worldwide. Novel imaging techniques are able to further characterize tumors and even predict histopathology features. Texture analysis is an emergent imaging technique to extract extensive data from an radiology images. The present study was therefore conducted to identify possible associations between texture analysis and histopathology parameters in thyroid cancer. METHODS: The radiological database was retrospectively reviewed for thyroid carcinoma. Overall, 13 patients (3 females, 23.1%) with a mean age of 61.6 years were identified. The MaZda program was used for texture analysis. The T1-precontrast and T2-weighted images were analyzed and overall 279 texture feature for each sequence was investigated. For every patient cell count, Ki67 index and p53 count were investigated. RESULTS: Several significant correlations between texture features and histopathology were identified. Regarding T1 weighted images, S(0;1)Sum Averg correlated the most with cell count (r=0.82). An inverse correlations with S(5;0)AngScMom, S(5;0)DifVarnc S(5;0), DiffEntrp and GrNonZeros (r=-0.69, -0.66, -0.69 and -0.63, respectively) was also identified. For T2-weighted images, Variance with r=0.63 was the highest coefficient, WavEnLL_S3 correlated inversely with cell count (r=-0.57). WavEnLL_S2 derived from T1-weighted images was the highest coefficient r=-0.80, S(0;5)SumVarnc was positively with r=0.74. Regarding T2-weighted images WavEnHL_s-1 was inverse correlated with Ki67 index (r=-0.77). S(1;0)Correlat was with r=0.75 the best correlation with Ki67 index. For T1-weighed images S(5;0)SumofSqs was the best with r=0.65 with p53 count. For T2-weighted images S(1;-1)SumEntrp was the inverse correlation with r=-0.72, whereas S(0;4)AngScMom correlated positively with r=0.63. CONCLUSIONS: MRI texture analysis derived from conventional sequences reflects histopathology features in thyroid cancer. This technique might be a novel noninvasive modality to further characterize thyroid cancer in clinical oncology. PMID- 28987631 TI - Ovariectomy modify local renin-angiotensin-aldosterone system gene expressions in the heart of ApoE (-/-) mice. AB - AIMS: The evaluation of the local Renin-Angiotensin-Aldosterone system (RAAS) gene expressions in the heart of ovariectomized (OVX) apolipoprotein E deficient mice (ApoE). METHODS: Four-months old C57BL/6 female mice (wild-type, wt, n=20), and ApoE female mice (n=20), were submitted to OVX or a surgical procedure without ovary removal (SHAM) and formed four groups (n=10/group): SHAM/wt, SHAM/ApoE, OVX/wt, and OVX/ApoE. KEY FINDINGS: OVX led to greater body mass, plasma triglycerides (TG) and total cholesterol, and resulted in insulin resistance and altered RAAS gene expressions in the heart tissue. The gene expression of angiotensin-converting enzyme (ACE)-2 was lower in OVX/wt than in SHAM/wt (P=0.0004), Mas receptor (MASr) was lower in OVX/wt compared to SHAM/wt (P<0.0001). Also, angiotensin II receptor type 1 (AT1r) was higher in OVX/wt than in SHAM/wt (P=0.0229), and AT2r was lower in OVX/wt than in SHAM/wt (P=0.0121). OVX and ApoE deficiency showed interaction potentializing the insulin resistance, increasing TG levels and altering ACE and MASr gene expressions. ACE gene expression was higher in OVX/ApoE than in OVX/wt (P<0.0001), and MASr gene expression was lower in OVX/ApoE than in OVX/wt (P<0.0001). SIGNIFICANCE: The impact of OVX on local RAAS cascade in the heart of ApoE deficient animals, besides the metabolic changes culminating with insulin resistance, involves an upregulation of renin, ACE, and AT1r gene expressions. The findings may contribute to clarify the mechanisms of development of postmenopausal hypertension and the link between RAAS and apolipoprotein E. PMID- 28987632 TI - Moderate hyperhomocysteinemia induced by short-term dietary methionine overload alters bone microarchitecture and collagen features during growth. AB - AIMS: In general, hyperhomocysteinemia is increasingly appreciated as a risk factor for various diseases, including osteoporosis. However, its effects in non adults remain largely unknown. Our aim was to determine whether dietary-caused increased homocysteine levels have deleterious effects on bone structure during growth. MAIN METHODS: We developed a model of moderate hyperhomocysteinemia caused by short-term methionine nutritional overload in growing rats. 30-days-old male Wistar albino rats were randomly assigned to either experimental group subject to a 30-days hypermethionine diet or control group. High-resolution 3D assessment of bone geometry and microarchitecture, as well as fluorescence spectroscopic analysis of bone matrix were performed. KEY FINDINGS: Short-term moderate hyperhomocysteinemia (~30MUmol/L) achieved in the study notably affected bone and cartilage characteristics. Parameters of the cortical bone geometry in the experimental group indicated peculiar reorganization of the bone cross section. Trabecular bone microarchitecture was especially sensitive to hyperhomocysteinemia showing clearly negative bone balance in the experimental group (almost 30% reduced bone volume, mainly due to ~25% decrease in trabecular number as well as markedly reduced trabecular connections). Fluorescent spectroscopy of bone matrix revealed multiple alterations to collagen spectra due to homocysteine accumulation in bone, indicative of broken collagenous cross links. SIGNIFICANCE: Given that appropriate accrual of bone mass during growth has important effects on the risk of osteoporosis in adulthood, understanding the skeletal effects of dietary-induced hyperhomocysteinemia in non-adults is essential for interpreting its importance as a modifiable risk factor for osteoporosis and improving programs to preserve/re-establish bone health. PMID- 28987633 TI - Long non-coding RNAs as biomarkers and therapeutic targets: Recent insights into hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer worldwide, and the survival rates of patients with HCC remains quite low after 5years. Long non-coding RNAs (LncRNAs) are a novel class of non-coding RNAs that are capable of regulating gene expression at various levels. Recent works have demonstrated that lncRNAs are often dysregulated in HCC, and the dysregulation of some of these lncRNAs are associated with the clinicopathological features of HCC. They regulate cell proliferation, apoptosis, autophagy, Epithelial Mesenchymal Transition (EMT), invasion and metastasis of HCC by modulating gene expression and cancer-related signaling pathways, and thus contribute to the onset and progression of HCC. In this review, we provide a comprehensive survey of dysregulated lncRNAs in HCC, with particular focus on the functions and regulatory mechanisms of several essential and important lncRNAs, and discuss their potential clinical application as early diagnostic and/or prognostic biomarkers or therapeutic targets for HCC. PMID- 28987634 TI - Heterodimerization of apelin and opioid receptors and cardiac inotropic and lusitropic effects of apelin in 2K1C hypertension: Role of pERK1/2 and PKC. AB - AIMS: Kappa Opioid receptors (KORs) change the impact of apelin on the phosphorylated ERK1/2 (pERK1/2). However, the role of interaction between KOR and apelin receptors (APJ) on the cardiac contractility effects of apelin and in regulation of pERK1/2 and PKC in the heart of renovascular hypertensive (2K1C) rats is unknown. MAIN METHODS: Hemodynamic factors, the heterodimerization of KOR and APJ, the expression of KOR mRNA and protein and pERK1/2 in the left ventricle of 2K1C rats were measured following APJ, KOR, PKC and Gi path inhibition by F13A, nor-BNI, chelerythrine and PTX respectively. KEY FINDINGS: Apelin in 40 and 60MUg/kg doses increased cardiac contractility, and reduced mean arterial pressure. The cardiac impacts in both doses were reduced by F13A, nor-BNI and chelerytrine and blocked by PTX. Hypertension increased the expression of KORs and heterodimerization of APJ and KOR, and reduced pERK1/2 in the left ventricle. Apelin, in both doses reduced (normalized) heterodimerization and recovered the reduction in pERK1/2. The recovery of ERK1/2 phosphorylation was accompanied by reduction of KOR and APJ heterodimerization. SIGNIFICANCE: 2K1C hypertension increased the expression of KORs and heterodimerization of APJ and KORs. The heterodimerization was associated by reduction of ERK phosphorylation and altered the cardiac inotropic and lusitropic effects of apelin. These changes may participate in pathophysiology of cardiac dysfunction in renovascular hypertension that is associated with subnormal level of serum apelin. Apelin- induced recovery of ERK1/2 phosphorylation and KOR-APJ dimerization may nominate apelin as a therapeutic goal in treatment of this kind of hypertension. PMID- 28987635 TI - Medicaid Expansion and Disparity Reduction in Surgical Cancer Care at High Quality Hospitals. AB - BACKGROUND: The Affordable Care Act's Medicaid expansion has been heavily debated due to skepticism about Medicaid's ability to provide high-quality care. Particularly, little is known about whether Medicaid expansion improves access to surgical cancer care at high-quality hospitals. To address this question, we examined the effects of the 2001 New York Medicaid expansion, the largest in the pre-Affordable Care Act era, on this disparity measure. STUDY DESIGN: We identified 67,685 nonelderly adults from the New York State Inpatient Database who underwent select cancer resections. High-quality hospitals were defined as high-volume or low-mortality hospitals. Disparity was defined as model-adjusted difference in percentage of patients receiving operations at high-quality hospitals by insurance type (Medicaid/uninsured vs privately insured) or by race (African American vs white). Levels of disparity were calculated quarterly for each comparison pair and then analyzed using interrupted time series to evaluate the impact of Medicaid expansion. RESULTS: Disparity in access to high-volume hospitals by insurance type was reduced by 0.97 percentage points per quarter after Medicaid expansion (p < 0.0001). Medicaid/uninsured beneficiaries had similar access to low-mortality hospitals as the privately insured; no significant change was detected around expansion. Conversely, racial disparity increased by 0.87 percentage points per quarter (p < 0.0001) in access to high volume hospitals and by 0.48 percentage points per quarter (p = 0.005) in access to low-mortality hospitals after Medicaid expansion. CONCLUSIONS: Pre-Affordable Care Act Medicaid expansion reduced the disparity in access to surgical cancer care at high-volume hospitals by payer. However, it was associated with increased racial disparity in access to high-quality hospitals. Addressing racial barriers in access to high-quality hospitals should be prioritized. PMID- 28987636 TI - Transcriptome mining for phylogenetic markers in a recently radiated genus of tropical plants (Renealmia L.f., Zingiberaceae). AB - The reconstruction of relationships within species-rich groups that have recently evolved in biodiversity hotspots is hampered by a lack of phylogenetically informative markers. It is also made difficult by the lack of sampling necessary to reconstruct a species-level phylogeny. We use transcriptome mining to search for markers to reconstruct a phylogeny of the amphi-Atlantic genus Renealmia L. f. (Zingiberaceae). We recover seven introns from single copy genes and use them to reconstruct the phylogeny of the genus together with a commonly used phylogenetic marker, internal transcribed spacers of ribosomal DNA (ITS) that has previously been used to reconstruct the phylogeny of the genus. We targeted genes with low numbers of base pairs that improves sequencing success using highly degraded DNA from herbarium specimens. The use of herbarium specimens greatly increased the number of species in the study as these were readily available in historical collections. Data were obtained for 14 of the 17 African species and 54 of the 65 Neotropical species. The phylogeny was well-supported for a number of Renealmia subgroups although relationships among those clades remained poorly supported. PMID- 28987637 TI - A comprehensive phylogeny of the genus Kurixalus (Rhacophoridae, Anura) sheds light on the geographical range evolution of frilled swamp treefrogs. AB - Currently, the genus Kurixalus comprises 14 species distributed in Southern, Southeast and East Asia. Because of their relatively low dispersal capability and intolerance of seawater, this group is ideal for the study of terrestrial range evolution, especially that portion of its range that extends into the island archipelagos of Southern Asia. We assembled a large dataset of mitochondrial and nuclear genes, and estimated phylogeny by maximum likelihood and Bayesian methods, and we explored the history of each species via divergence-time estimation based on fossil-calibrations. A variety of ancestral-area reconstruction strategies were employed to estimate past changes of the species' geographical range, and to evaluate the impact of different abiotic barriers on range evolution. We found that frilled swamp treefrogs probably originated in Taiwan or South Vietnam in the Oligocene. Alternatively, the lineage leading to Kurixalus appendiculatus strongly supports a hypothesis of terrestrial connection between the Indian and Asian continents in the Oligocene. The outcome of both our divergence-time estimates and ancestral-area reconstruction suggests that the divergence between species from Indochina and Taiwan can probably be attributed to the opening of the South China Sea, approximately 33 million years ago. We could not find evidence for dispersal between mainland China and Taiwan Island. Formation of both Mekong and Red River valleys did not have any impact on Kurixalus species diversification. However, coincidence in timing of climate change and availability of plausible dispersal routes from the Oligocene to the middle Miocene, plausibly implied that Kurixalus diversification in Asia resulted from contemporaneous, climate-induced environmental upheaval (Late Oligocene Warming at 29 Ma; Mi-1 glaciation since 24.4-21.5 Ma; Mid-Miocene Climatic Optimum at 14 Ma), which alternatively opened and closed dispersal routes. PMID- 28987638 TI - Adaptive radiations should not be simplified: The case of the danthonioid grasses. AB - Although much of extant diversity is probably the product of evolutionary radiations, the special case of adaptive radiations has not yet been thoroughly explored. Adaptive radiations are postulated to occur when a lineage is exposed to new ecological opportunities, where it can diversify ecologically. We argue that adaptive radiations have two characteristics. Firstly, the diversification rate accelerates initially, and is then followed by a density-dependent slow down. Secondly, traits relevant to the new ecological opportunity should evolve at or just before the radiation. We also argue that a correct identification of adaptive radiations is dependent on the phylogenies underlying the diversification dynamics being sampled adequately (i.e. comprehensive species sampling), and that the traits should be treated continuously if they exhibit a biological continuum and not be over-simplified into binary traits. Here, we test the hypothesis that much of the extant diversity of the south-temperate grass subfamily Danthonioideae is the result of two geographically separated but contemporaneous adaptive radiations, in response to Late-Miocene-Pliocene aridification and increasingly seasonal climates. We show that both Pentameris (83 African species) and Rytidosperma (73 Australasian-South American species) exhibit accelerations in diversification rates followed by linear density dependent declines. We also show that two selected traits show differential evolutionary regimes with different evolutionary optima, and that these are linked to changes in the diversification rate. These results are consistent with these being adaptive, and putatively parallel, radiations. However, by mapping traits over the whole danthonioid phylogeny, it is evident that no identified trait or trait combination is sufficient and necessary for adaptive radiations. Furthermore, we show that simplifying the traits to binary gives a strong but potentially erroneous link between trait shift and diversification rate shift. PMID- 28987639 TI - Mismatch between suspected pyelonephritis and microbiological diagnosis: a cohort study from a UK teaching hospital. AB - Urinary tract infections are a common reason for prescribing empirical antibiotics in the emergency department. This study investigated the role of microbiological culture and urinalysis in the diagnosis of pyelonephritis by extracting data on 105 patients with a clinical diagnosis of pyelonephritis at a London teaching hospital. In total, 99 of 102 patients were treated empirically with intravenous antibiotics, but only 55 of 100 patients who were sampled had microbiological evidence of infection in urine and/or blood. Almost half (10/21) of the patients with a negative urine dipstick test had a positive urine culture. Diagnostic uncertainty in this context undoubtedly drives inappropriate antibiotic use. PMID- 28987640 TI - Pseudomonas aeruginosa control in healthcare settings: outpatient dialysis units are not augmented care units. PMID- 28987641 TI - Flocked nylon swabs versus RODAC plates for detection of multidrug-resistant organisms on environmental surfaces in intensive care units. AB - To compare two culture methods [nylon fiber flocked swabs with broth enrichment versus RODAC ('replicate organism detection and counting') plates] for recovery of multidrug-resistant organisms, 780 environmental surfaces in 63 rooms of patients on contact precautions in four intensive care units at one hospital were examined. Among sites that had at least one positive culture, swab culture with broth enrichment detected the target organisms more frequently than RODAC plates (37.5% vs 26.0%, P = 0.06). There was moderate agreement between the two methods (kappa = 0.44) with agreement better for small or flat surfaces compared to large or irregular surfaces. PMID- 28987642 TI - Handgrip strength shows no improvements in geriatric patients with persistent inflammation during hospitalization. AB - PURPOSE: Hospital-associated deconditioning due to a combination of illness and inactivity is a serious problem for elderly adults. Here we investigate whether persistence in inflammatory status affects changes in physical function during short-term hospitalization. METHODS: This was a prospective observational study in elderly medical patients at a geriatric department. Measurements were obtained at admission and one week after admission and included de Morton Mobility Index (DEMMI) test, 30-second chair stand test (30-s CST), 4-m gait speed (4-m GST) test, handgrip strength, activity levels determined with ActivPALs, and concentrations of circulating C-reactive protein (CRP) from blood samples. Only patients with inflammation (C-reactive protein levels >=10mg.L-1) at admission were included in this study. They were divided into those with continued inflammation (CI: CRP remained >=10mg.L-1) and those that became non-inflammatory (BN: CRP decreased to <10mg.L-1) after one week of admission. RESULTS: On admission 214 patients (67% female) with a median (IQR) age of 86 (81-91) years were categorized as inflammatory. There were no baseline differences in physical function between CI (n=138, 67% female) and BN (n=76, 68% female). DEMMI-score increased similarly in both groups (P<0.05). When normalized to days between tests, only changes in handgrip strength were significantly different between the CI- and BN-group (-0.05 [-0.27-0.28] vs. 0.16 [-0.10-0.41] kg.day-1, respectively, P<0.01). There was a positive association between changes in CRP and length of hospital stay (rs=0.30, P<0.001). CONCLUSION: Hospitalized geriatric patients admitted with inflammation showed only moderate improvement of general mobility during hospital stay, regardless of changes in their inflammatory status. However, handgrip strength increased only in those patients who became non-inflammatory during hospitalization. PMID- 28987644 TI - Considerations for successful cancer immunotherapy in aged hosts. AB - Improvements in understanding cancer immunopathogenesis have now led to unprecedented successes in immunotherapy to treat numerous cancers. Although aging is the most important risk factor for cancer, most pre-clinical cancer immunotherapy studies are undertaken in young hosts. This review covers age related immune changes as they affect cancer immune surveillance, immunopathogenesis and immune therapy responses. Declining T cell function with age can impede efficacy of age-related cancer immunotherapies, but examples of successful approaches to breach this barrier have been reported. It is further recognized now that immune functions with age do not simply decline, but that they change in potentially detrimental ways. For example, detrimental immune cell populations can become predominant during aging (notably pro-inflammatory cells), the prevalence or function of suppressive cells can increase (notably myeloid derived suppressor cells), drugs can have age-specific effects on immune cells, and attributes of the aged microenvironment can impede or subvert immunity. Key advances in these and related areas will be reviewed as they pertain to cancer immunotherapy in the aged, and areas requiring additional study and some speculations on future research directions will be addressed. We prefer the term Age Related Immune Dysfunction (ARID) as most encompassing the totality of age associated immune changes. PMID- 28987643 TI - Blood flow restricted resistance training in older adults at risk of mobility limitations. AB - : High-load resistance training (HL) may be contraindicated in older adults due to pre-existing health conditions (e.g. osteoarthritis). Low-load blood flow restricted (BFR) resistance training offers an alternative to HL with potentially similar strength improvement. PURPOSE: To compare muscle strength, cross sectional area (CSA), physical function, and quality of life (QOL) following 12 weeks of HL or BFR training in older adults at risk of mobility limitations. METHODS: Thirty-six males and females (mean: 75.6years 95% confidence interval: [73.4-78.5], 1.67m [1.64-1.70], 74.3kg [69.8-78.8]) were randomly assigned to HL (70% of one repetition maximum [1-RM]) or low-load BFR (30% 1-RM coupled with a vascular restriction) exercise for the knee extensors and flexors twice per week for 12weeks. A control (CON) group performed light upper body resistance and flexibility training. Muscle strength, CSA of the quadriceps, 400-m walking speed, Short Physical Performance Battery (SPPB), and QOL were assessed before, midway and after training. RESULTS: Within 6-weeks of HL training, increases in all strength measures and CSA were evident and the gains were significantly greater than the CON group (P<0.05). The BFR group had strength increases in leg extension and leg press 1-RM tests, but were significantly lower in leg extension isometric maximum voluntary contraction (MVC) and leg extension 1-RM than the HL group (P<0.01). At 12-weeks HL and BFR training did not differ in MVC (P=0.14). Walking speed increased 4% among all training groups (P<0.01) and no changes were observed for overall SPPB score and QOL (P>0.05). CONCLUSION: Both training programs resulted in muscle CSA improvements and HL training had more pronounced strength gains than BFR training after 6-weeks and were more similar to BFR after 12-weeks of training. These changes in both groups did not transfer to improvements in QOL, SPPB, and walking speed. Since both programs result in strength and CSA gains, albeit at different rates, future research should consider using a combination of HL and BFR training in older adults with profound muscle weakness and mobility limitations. PMID- 28987645 TI - Tumefactive demyelinating lesions (TDLs): A case series of clinicoradiological features. AB - OBJECTIVE: Diagnosis of tumefactive demyelination lesions (TDLs) is challenging to neurophysician, neuroradiologist or neurosurgeon. Our objective in this study was to analyze clinicoradiological features of TDLs. PATIENTS AND METHOD: A retrospective analysis with prospective follow-up of 11 cases of TDLs was performed. Study was conducted in the neurology department of a tertiary care centre of North-West India from August 2014 to March 2017. MRI of brain and cervical spine with contrast, visual evoked potential, oligoclonal bands, serum anti-AQP4 antibody and MRS performed in most of the patients. RESULTS: Mean age of tumefactive demyelinating lesions was 19.63 years (10-41) with male preponderance (M: F=1.4) and one of the patients was in a pediatric age group. Relapsing and demyelinating courses of disease, seizure and incomplete ring enhancement were found in 6 out of 11(54.5%), 4 out of 11 (36.3%) 3 out of 11(27.2) respectively. OCBs were positive in 4 out of 5 patients (80%). CONCLUSION: Recognition of atypical presentation or clinicoradiological features would aid in diagnosis along with visual evoked potential, oligoclonal bands and responsiveness to steroids may obviate the need for invasive procedure like brain biopsy. PMID- 28987646 TI - Molecular cloning and expression of Octamer-binding transcription factor (Oct4) in the large yellow croaker, Larimichthys crocea. AB - Octamer-binding transcription factor 4 (Oct4) is a crucial pluripotent transcription factor in controlling pluripotency of embryonic stem cells (ESCs), formation of primordial germ cells (PGCs), early embryonic development, and gonadal germ cells. To understand the roles of Oct4 in the large yellow croaker (Larimichthys crocea) (Lc-Oct4), the full-length cDNA of Oct4 was cloned and analyzed. Lc-Oct4 includes a 104-bp 5' untranslated region (UTR), a 567-bp 3' UTR and a 1431-bp coding region encoding a protein of 476 amino acids (aa) with a predicted molecular mass (Mm) of 52.40 kDa and an isoelectric point (PI) of 6.34. Quantitative real time PCR (qRT-PCR) in tissues showed that Lc-Oct4 was only expressed in ovary. During ovarian development, the expression level in 635 days post hatching (635-dph) ovary was about 6.3-fold higher than in 270-dph and 1000 dph ovary. The in situ hybridization analysis showed that Lc-Oct4 had a high expression in the different developmental stages of oocytes with the highest level in stages II (later) and III oocytes. Lc-Oct4 was also expressed in spermatogonia and primary spermatocytes. Furthermore, the qRT-PCR analysis of Lc Oct4 in different developmental embryos revealed that the expression from high to low was multiple-cell stage > mid-blastula stage = mid-gastrula stage, and the expression in multiple-cell stage was at less 1.6-fold higher than in other stages. Accordingly, the whole mount in situ hybridization (WISH) in embryos demonstrated that Lc-Oct4 was expressed only in early embryonic development from 2-cell stage to early-gastrula stage with the peak at 16-cell stage, but not detected in PGCs area. In conclusion, Lc-Oct4 participated in the oogenesis and early embryonic development in large yellow croaker. Overall, this study provided better understanding of Lc-Oct4 gene and lay the foundation for its function research in the large yellow croaker. PMID- 28987647 TI - Serpin-9 and -13 regulate hemolymph proteases during immune responses of Manduca sexta. AB - Serpins are a superfamily of proteins, most of which inhibit cognate serine proteases by forming inactive acyl-enzyme complexes. In the tobacco hornworm Manduca sexta, serpin-1, -3 through -7 negatively regulate a hemolymph serine protease system that activates precursors of the serine protease homologs (SPHs), phenoloxidases (POs), Spatzles, and other cytokines. Here we report the cloning and characterization of M. sexta serpin-9 and -13. Serpin-9, a 402-residue protein most similar to Drosophila Spn77Ba, has R366 at the P1 position right before the cleavage site; Serpin-13, a 444-residue ortholog of Drosophila Spn28Dc, is longer than the other seven serpins and has R410 as the P1 residue. Both serpins are mainly produced in fat body and secreted into plasma to function. While their mRNA and protein levels were not up-regulated upon immune challenge, they blocked protease activities and affected proPO activation in hemolymph. Serpin-9 inhibited human neutrophil elastase, cathepsin G, trypsin, and chymotrypsin to different extents; serpin-13 reduced trypsin activity to approximately 10% at a molar ratio of 4:1 (serpin: enzyme). Serpin-9 was cleaved at Arg366 by the enzymes with different specificity, but serpin-13 had four P1 sites (Arg410 for trypsin-like proteases, Gly406 and Ala409 for the elastase and Thr404 for cathepsin G). Supplementation of induced cell-free hemolymph (IP, P for plasma) with recombinant serpin-9 did not noticeably affect proPO activation, but slightly reduced the PO activity increase after 0-50% ammonium sulfate fraction of the IP had been elicited by bacteria. In comparison, addition of recombinant serpin-13 significantly inhibited proPO activation in IP and the suppression was stronger in the fraction of IP. Serpin-9- and -13-containing protein complexes were isolated from IP using their antibodies. Hemolymph protease-1 precursor (proHP1), HP6 and HP8 were found to be associated with serpin-9, whereas proHP1, HP2 and HP6 were pulled downed with serpin-13. These results indicate that both serpins regulate immune proteases in hemolymph of M. sexta larvae. PMID- 28987648 TI - Patients' comprehension and skill usage as a putative mediator of change or an engaged target in cognitive therapy: Preliminary findings. AB - BACKGROUND: The skills that patients learn in cognitive therapy (CT) and use thereafter may mediate improvement in depression during and after intervention. METHOD: We used a sequential, three-stage design: acute phase (523 outpatients received 12-14 weeks of CT); 8-month experimental phase (responders at higher risk were randomized to continuation phases: C-CT, C-fluoxetine or C-pill placebo); and 24 months of longitudinal, post-treatment follow-up. Path analyses estimated mediation by skill measured by the Skills of Cognitive Therapy (SoCT: Patient and Observer [Therapist] versions). RESULTS: Better SoCT scores predicted lower depressive symptoms both in CT and C-CT. In CT depressive symptoms did not predict subsequent changes in skills. During CT and C-CT, when averaged across patients and therapists, skills predicted subsequent decreases in depressive symptoms. LIMITATIONS: Generalization of findings may be limited by the trial's methodology. CONCLUSION: Further rigorous investigation of the role of patient CT skills stands to increase understanding of mediators of change or engaged targets in psychosocial intervention. PMID- 28987649 TI - Comparison of Laparoscopic Discoid Resection and Segmental Resection for Colorectal Endometriosis Using a Propensity Score Matching Analysis. AB - STUDY OBJECTIVE: Our primary endpoint was to compare the intra- and postoperative complications, whereas secondary endpoints were the occurrence of voiding dysfunction and evaluation of the quality or life of segmental and discoid resection in patients with colorectal endometriosis. DESIGN: Retrospective study (Canadian Task Force classification II-2). SETTING: Tenon University Hospital in Paris. PATIENTS: Thirty-one 31 patients who underwent a conservative surgery and 31 patients who underwent. INTERVENTIONS: The 2 groups were compared using propensity score matching (PSM) analysis, with a median follow-up of 247 days (8.2 months). MEASUREMENTS AND MAIN RESULTS: Discoid colorectal resection was associated with a shorter operating time (155 vs 180 minutes, p = .03) and hospital stay (7 vs 8 days, p = .002) than segmental colorectal resection; however, a similar intra- and postoperative complication rate was found. A higher rate of postoperative voiding dysfunction was observed in the segmental resection group (19% vs 45%, p = .03) as well as duration of voiding dysfunction requiring bladder self-catheterization longer than 30 days (0 vs 22%, p = .005). CONCLUSION: Our PSM analysis suggests the advantages of discoid resection because it results in a similar surgical complication rate to segmental resection but with advantages in operating time, hospital stay, and voiding dysfunction. PMID- 28987651 TI - Ultrastructure and Phylogeny of Kirithra asteri gen. et sp. nov. (Ceratoperidiniaceae, Dinophyceae) - a Free-Living, Thin-Walled Marine Photosynthetic Dinoflagellate from Argentina. AB - A gymnodinioid photosynthetic dinoflagellate was isolated from Argentina and examined by light and electron microscopy and analysis of nuclear-encoded LSU rDNA. Kirithra asteri gen. et sp. nov. was proposed as morphology and molecular phylogeny separated this dinoflagellate from others within the family Ceratoperidiniaceae. Cells were surrounded by a hyaline amphiesma comprising polygonal vesicles. Each vesicle contained a honeycomb and a trilaminar structure. An anterior sulcal extension ending in a complete circle formed the apical structure complex (ASC), which characterizes Ceratoperidiniaceae. The ASC comprised three rows of vesicles. The nucleus was located in the hypocone, and several large, irregularly shaped vesicles were present in the epi- and hypocone. Chloroplasts were surrounded by three membranes, and grana-like arrangements of thylakoids were observed in one strain used for ultrastructural study. The cell centre contained 1-3 multiple-stalked pyrenoids and membrane-bound vesicles containing tile-like structures surrounded each pyrenoid. Two pusules with collecting chambers and associated vesicles branched off each of the flagellar canals. The flagellar apparatus featured a ventral connective between the amphiesma and the R1 root, and almost opposite basal bodies, rarely seen in dinoflagellates. This was the first ultrastructural study of a species within Ceratoperidiniaceae. PMID- 28987650 TI - The effects of air pollution on individual psychological distress. AB - This study is the first of its kind to utilize longitudinal, nationally representative panel data from the United States to assess the relationship between exposure to air pollution and reports of psychological distress. Using annual-average measures of air pollution in respondents' census blocks of residence we find that over the period 1999-2011 particulate matter 2.5 is significantly associated with increased psychological distress; this association remains even after controlling for a robust set of demographic, socioeconomic, and health-related covariates. This study suggests that public health efforts to reduce the personal and societal costs of mental illness should consider addressing not only individual characteristics and factors in the social environment, but also underexplored facets of the physical environment such as air pollution. PMID- 28987653 TI - Diagnostic hierarchy of radiological features in soft tissue tumours and proposition of a simple diagnostic algorithm to estimate malignant potential of an unknown mass. AB - OBJECTIVE: To quantify the diagnostic utility of imaging features in soft tissue masses (STMs) and to provide a ranked list of predictors for malignancy. SUBJECTS AND METHODS: Imaging features in 260 cases of STMs with verified histology were assessed. Diagnostic properties including sensitivity, specificity, positive and negative predictive values, likelihood/odds ratios (OR) and normalized variance (NV) via random forest analysis were calculated. The diagnostic utility of an 8 item checklist consisting of the highest-ranked features was evaluated through a receiver-operating-characteristics (ROC) curve. RESULTS: The most predictive features (NV/OR in parentheses) were heterogeneous contrast-enhancement in ultrasound (297.9/15.1) and MRI (197.3/11.9), lesion roundness (209.8/5.5), diffusion restriction (175.8/9.3), cystic/necrotic intralesional areas (167.1/8.3), higher patient age (159.0/2.6), surrounding oedema (155.4/6.5) and intralesional Doppler hypervascularity (134.4/5.1). A simple 8-item checklist was highly predictive of malignancy in cases with at least 75% positive features (0.90 area under the ROC curve, 87.0% sensitivity, 84.5% specificity, 59.5% positive and 96.1% negative predictive value, 36.5 odds ratio) even in cases with only partial feature availability. CONCLUSION: Features vary widely in their diagnostic value in STMs; an 8-item checklist based on the eight most decisive features can be a simple tool to assess the likelihood for malignancy in unknown soft tissue masses, even though a stratified approach is certainly still advisable when first confronted with an STM. PMID- 28987652 TI - Dual-energy computed tomography in patients with cutaneous malignant melanoma: Comparison of noise-optimized and traditional virtual monoenergetic imaging. AB - OBJECTIVE: The aim of this study was to investigate the impact of noise-optimized virtual monoenergetic imaging (VMI+) reconstructions on quantitative and qualitative image parameters in patients with cutaneous malignant melanoma at thoracoabdominal dual-energy computed tomography (DECT). MATERIALS AND METHODS: Seventy-six patients (48 men; 66.6+/-13.8years) with metastatic cutaneous malignant melanoma underwent DECT of the thorax and abdomen. Images were post processed with standard linear blending (M_0.6), traditional virtual monoenergetic (VMI), and VMI+ technique. VMI and VMI+ images were reconstructed in 10-keV intervals from 40 to 100keV. Attenuation measurements were performed in cutaneous melanoma lesions, as well as in regional lymph node, subcutaneous and in-transit metastases to calculate objective signal-to-noise (SNR) and contrast to-noise (CNR) ratios. Five-point scales were used to evaluate overall image quality and lesion delineation by three radiologists with different levels of experience. RESULTS: Objective indices SNR and CNR were highest at 40-keV VMI+ series (5.6+/-2.6 and 12.4+/-3.4), significantly superior to all other reconstructions (all P<0.001). Qualitative image parameters showed highest values for 50-keV and 60-keV VMI+ reconstructions (median 5, respectively; P<=0.019) regarding overall image quality. Moreover, qualitative assessment of lesion delineation peaked in 40-keV VMI+ (median 5) and 50-keV VMI+ (median 4; P=0.055), significantly superior to all other reconstructions (all P<0.001). CONCLUSION: Low-keV noise-optimized VMI+ reconstructions substantially increase quantitative and qualitative image parameters, as well as subjective lesion delineation compared to standard image reconstruction and traditional VMI in patients with cutaneous malignant melanoma at thoracoabdominal DECT. PMID- 28987654 TI - High-resolution ultrasound in etiological evaluation of ulnar neuropathy at the elbow. AB - OBJECTIVE: Ulnar neuropathy at the elbow (UNE) involves mechanical compression and irritation of the ulnar nerve (UN) caused by environmental and dynamic abnormalities that can however also be found in asymptomatic patients. Using high resolution ultrasound, we aimed to assess and compare the relevance of morphological and dynamic variants of the UN and its surrounding structures (UN abnormalities) in symptomatic and asymptomatic patients. METHOD: UN abnormalities in patients with UNE were assessed using high-resolution ultrasound and compared against unaffected arms (patients or healthy volunteers). RESULTS: We studied 234 arms of 117 individuals (89 with UNE and 145 control). Eighty-one percent of the arms with UNE compared to 40% of control (p=0.00001) showed UN abnormalities. While it was dislocated in 49% of arms with UNE compared to in 23% of control (p=0.004). CONCLUSION: The two-fold higher frequency of occurrence of UN abnormalities in arms with UNE indicates their causative or at least contributory role in such neuropathies. High-resolution ultrasound should be part of the initial evaluation of UNE in order to assess the etiology of the conflict. PMID- 28987655 TI - Radiation dose reduction initiative: Effect on image quality in shoulder CT imaging. PMID- 28987656 TI - Meta-analysis of dual-energy computed tomography virtual non-calcium imaging to detect bone marrow edema. AB - OBJECTIVE: This meta-analysis aimed to evaluate the accuracy of dual-energy CT (DECT) virtual non-calcium (VNC) imaging for the detection of bone marrow edema (BME). METHODS: A systematic literature search up to March 2017 was performed to find relevant original studies. Two reviewers independently selected studies, assessed literature quality, and extracted data. Pooled sensitivity, specificity, area under receiver operating characteristic (AUROC) curve, and other measures of DECT accuracy for detecting BME were calculated using random effects models. Risk of heterogeneity was assessed for the appropriateness of meta-analysis. RESULTS: Fourteen studies involving 2205 regions of vertebrae, hips, knees, and ankles were included. To evaluate the accuracy of BME detection using DECT, calculations were performed to obtain a pooled sensitivity of 0.812 (95% confidence interval [CI], 0.780-0.841) and specificity of 0.951 (95% CI, 0.940-0.960). The AUROC value was 0.9635. The major potential cause of heterogeneity was bone position. No significant publication bias was present. CONCLUSION: DECT VNC imaging gives very good diagnostic performance for BME detection and will likely be an important and common modality for acute assessment in the future. PMID- 28987657 TI - Feasibility of percutaneous cryoablation of vertebral metastases under local anaesthesia in ASAIII patients. AB - PURPOSE: spine metastases are common concern from several primary neoplasms, modern management include percutaneous techniques such as ablation and cementoplasty. This research aims to evaluate the treatment under local anaesthesia in high-risk patients (ASA III). METHODS AND MATERIAL: from January 2013 up to September 2016 we treated via percutaneous cryoablation 11 advanced oncological patients classified as ASA III, then retrospectively a review of their clinical history has been performed. Interventions were managed under local anaesthesia, injecting low doses of bupivacaine 2,5mg/ml (from10 to 30ml). Cryoprobes of 17G were introduced under CT guidance. VAS scores were evaluated pre, intra and post operative up to the 3rd month and further, statistical analyses were obtained using T student test. RESULTS: thirteen spinal metastases were cryoablated in 11 patients (6W, 5M; mean age of 53 years, range 52-81). Tumour location was: sacrum (n=6), lumbar spine (n=3), thoracic spine (n=2). The average VAS value during the procedure was 5,27 (standard deviation 0,90). There were statistically significant decreases in the median numeric VAS scale score at 1-week, 1-month, and 3-month time points (P<.001 for all). Technical success was achieved in all cases. Among patients with neurological deficit, some clinical improvement was assessed. CONCLUSION: cryoablation with or without subsequent cement injection can be safely performed with local anaesthesia for pain relief also in patients with high ASA score with higher risk of complications, in the absence of any other suitable treatment. PMID- 28987658 TI - Magnetic resonance and ultrasound in achilles tendinopathy: Predictive role and response assessment to platelet-rich plasma and adipose-derived stromal vascular fraction injection. AB - OBJECTIVE: To assess the correlation between magnetic resonance and ultrasound findings and clinical outcome after intratendinous injection of leucocyte-rich platelet-rich plasma or adipose-derived stromal vascular fraction in patients with non-insertional Achilles tendinopathy. MATERIALS AND METHODS: Forty-three patients (age: 47.8+/-5.1, range 29-55) with unilateral or bilateral non insertional Achilles tendinopathy (58 tendons overall) were randomly assigned to platelet-rich plasma (22 patients, 28 tendons) or adipose-derived stromal vascular fraction (21 patients, 30 tendons) injection group. All patients underwent magnetic resonance (tendon cross-sectional area, signal intensity, maximum anteroposterior thickness were measured), ultrasound (maximum anteroposterior thickness, power Doppler signal, ultrasound gray scale echotexture were measured), and visual analogue scale (VAS) pain evaluation at baseline and at six months from treatment. Wilcoxon, intraclass correlation coefficient, repeated measure ANOVA tests were used. RESULTS: There was a significant (P<0.001) decrease of mean VAS from pre-treatment (6.4+/-1.4) to six month evaluation (1.8+/-1.7). Significant increase of tendon thickness measured using magnetic resonance (P=0.013) and ultrasound (P=0.012) and power Doppler signal (P=0.027) was seen. There was no significant difference between pre- and post-treatment cross sectional area, signal intensity, and echotexture (P>0.217). None of the pre-treatment parameters was a predictor of treatment outcome (P>0.104). There was an excellent agreement between tendon thickness measurement between magnetic resonance and ultrasound (intraclass correlation coefficient=0.986) CONCLUSIONS: Both treatments seem to allow for clinical benefit, associated to early slight increase of tendon size and power Doppler signal. Imaging cannot be used as a predictor of clinical outcome. PMID- 28987659 TI - Relationship between radiologist training level and radiation exposure for therapeutic hip injections. AB - OBJECTIVE: The aim of this study was to determine the relationship between the level of training of the performing radiologist and patient radiation exposure, as measured by fluoroscopy time (FT) and dose area product (DAP), during fluoroscopic guided hip injections. MATERIALS AND METHODS: This IRB-approved retrospective review of our institutional radiology report database identified all fluoroscopic guided hip injections performed between August 1st, 2012 and May 30th, 2015. Performing radiologists were divided into groups based on their level of training at the time of the procedure: first-year residents (R1), second-year residents (R2), third-year residents (R3), fourth-year residents (R4), staff fellowship trained musculoskeletal radiologists, and non-musculoskeletal radiologists. A mixed effects model was applied, using level of training as an independent predictor to model FT and DAP separately. RESULTS: There were 20, 19, 18 and 20 residents in the R1, R2, R3 and R4 groups, respectively. There were 5 performers in the non-MSK radiologist group, and 7 in the MSK radiologist group. A total of 1362 hip injection procedures met the inclusion criteria and were included in the analysis. The overall average FT was 26s (+/-17SD) and overall average DAP was 20.4uGy*m2 (+/-22.3SD). The mixed effects model showed no statistically significant difference between the groups, for FT (p=0.31) and for DAP (p=0.82). CONCLUSION: There is no association between radiologist level of training and patient radiation exposure for fluoroscopic hip injections. Resident trainees maintain radiation exposure to patients at levels comparable to their more experienced colleagues. PMID- 28987661 TI - Contamination artifact that mimics in-situ carcinoma on contrast-enhanced digital mammography. AB - PURPOSE: Contrast-enhanced digital mammography (CEDM) is an advanced breast imaging technique using iodinated intravenous contrast to detect breast cancer. This article describes imaging features of a skin contamination artifact on CEDM that mimics in-situ carcinoma in a case series. MATERIALS AND METHODS: Five patients were identified whose CEDM images demonstrated apparent calcifications and non-mass enhancement suspicious for in-situ carcinoma, with no subsequent evidence of disease. Retrospective image analysis was performed on the unprocessed image data, processed images, and imaging parameters. Dual-energy mammographic technique was performed on two breast phantoms with varying degrees of topical contrast contamination. RESULTS: Temporal analysis confirmed the suspicious finding was neither an abnormality of the compression paddle nor the receptor. Comparison of LE and HE images demonstrated the suspicious finding attenuated near the K-edge of iodine, suggesting contrast contamination. Iodinated contrast applied to the surface of breast phantoms replicated the artifact, with a pattern of apparent enhancement similar to the appearance of in situ carcinoma. CONCLUSION: Skin contamination with iodinated contrast can result in an artifact on post-contrast digital mammography that mimics the appearance of in-situ carcinoma. PMID- 28987660 TI - Partial anomalous pulmonary venous return in Turner syndrome. AB - PURPOSE: The aim of this study is to describe the prevalence, anatomy, associations and clinical impact of partial anomalous pulmonary venous return in patients with Turner syndrome. METHODS AND RESULTS: All Turner patients who presented at our Turner clinic, between January 2007 and October 2015 were included in this study and underwent ECG, echocardiography and advanced imaging such as cardiac magnetic resonance or computed tomography as part of their regular clinical workup. All imaging was re-evaluated and detailed anatomy was described. Partial anomalous pulmonary venous return was diagnosed in 24 (25%) out of 96 Turner patients included and 14 (58%) of these 24 partial anomalous pulmonary venous return had not been reported previously. Right atrial or ventricular dilatation was present in 11 (46%) of 24 partial anomalous pulmonary venous return patients. CONCLUSION: When studied with advanced imaging modalities and looked for with specific attention, PAPVR is found in 1 out of 4 Turner patients. Half of these patients had right atrial and/or ventricular dilatation. Evaluation of pulmonary venous return should be included in the standard protocol in all Turner patients. PMID- 28987662 TI - Value of DCE-MRI for staging and response evaluation in rectal cancer: A systematic review. AB - PURPOSE: Aim was to perform a systematic review to evaluate the clinical value of dynamic contrast-enhanced (DCE) MRI in rectal cancer. METHODS AND MATERIALS: A systematic search was performed on Pubmed, Embase and the Cochrane library. Studies that evaluated DCE-MRI for tumour aggressiveness, primary staging and restaging after chemoradiation (CRT) were included. Information on population, DCE technique, DCE parameters and outcome (angiogenesis, staging and response) were extracted. RESULTS: 19 studies were identified; 10 evaluated quantitative analyses, 6 semiquantitative analyses and 3 evaluated both. 8 studies evaluated correlation between DCE-parameters and angiogenesis or tumour aggressiveness, 11 studies evaluated response prediction pre- and post-CRT. Semiquantitative washin parameters showed a significantly positive correlation with angiogenesis, while for quantitative analyses conflicting results were found. Conflicting results were also reported for the correlation between DCE parameters and tumour aggressiveness: both higher and lower vascularity in more aggressive tumours are reported, while some studies report no correlation. Six studies showed a predictive value of Ktrans for response. A high Ktrans pre-CRT was significantly correlated with a complete/good response, but the reported pre-CRT Ktrans varied substantially (0.36-1.93). After CRT a reduction in Ktrans of 32%-36% was significantly associated with response. For semiquantitative analyses pre-CRT late slope was reported to be significantly lower in good responders, however only few studies exist on semiquantitative analyses of post-CRT DCE-MRI. CONCLUSION: DCE-MRI in rectal cancer is promising mainly for prediction and assessment of response to CRT, where a high pre-CRT Ktrans and a decrease in Ktrans are significantly predictive for response. PMID- 28987663 TI - Radiography, abdominal CT and MRI compared with sacroiliac joint CT in diagnosis of structural sacroiliitis. AB - OBJECTIVE: To assess the performance of pelvic plain radiograph (radiography), abdominal CT and sacroiliac joint MRI (MRI) compared with sacroiliac joints CT (SI joint CT) for the diagnosis of structural sacroiliitis in a population suffering from spondyloarthritis (SpA) meeting the New York or ASAS criteria. METHODS: All SpA patients eligible for biologic treatment who received a pre therapeutic check-up including the four imaging techniques in the same year were selected from 2005 to 2012. An assessment of sacroiliitis was based independently by a rheumatologist and a radiologist on radiography according to the modified New York criteria and on abdominal CT, MRI and SI Joint CT depending on the presence of erosion on at least two consecutive slices. A final diagnosis was established for conflicting exams. RESULTS: Of the 58 selected patients, sacroiliitis was diagnosed on radiography, abdominal CT, MRI and SI Joint CT in 32, 26, 34 and 35 patients, respectively. Inter-reader agreements for the grade of sacroiliitis were substantial with a weighted Kappa that varied between 0.60 and 0.76 and they were moderate for the diagnosis of sacroiliitis with a Kappa that varied between 0.45 and 0.55 for the four imaging modalities. The sensitivities of radiography, abdominal CT and MRI were 82.8%, 71.4% and 85.7% respectively and the specificities were 86.9%, 100% and 82.6% respectively with excellent accuracy and positive predictive value and good negative predictive value. CONCLUSION: This study demonstrates the relevance of MRI and abdominal CT for the diagnosis of structural sacroiliitis with good sensitivities and excellent specificities. These imaging modalities may also contribute for the diagnosis of structural sacroiliitis. PMID- 28987664 TI - Abbreviated breast magnetic resonance protocol: Value of high-resolution temporal dynamic sequence to improve lesion characterization. AB - PURPOSE: To evaluate the added value of ULTRAFAST-MR sequence to an abbreviated FAST protocol in comparison with FULL protocol to distinguish benign from malignant lesions in a population of women, regardless of breast MR imaging indication. MATERIALS AND METHODS: From March 10th to September 22th, 2014, we retrospectively included a total of 70 consecutive patients with 106 histologically proven lesions (58 malignant and 48 benign) who underwent breast MR imaging for preoperative breast staging (n=38), high-risk screening (n=7), problem solving (n=18), and nipple discharge (n=4) with 12 time resolved imaging of contrast kinetics (TRICKS) acquisitions during contrast inflow interleaved in a regular high-resolution dynamic MRI protocol (FULL protocol). Two readers scored MR exams as either positive or negative and described significant lesions according to Bi-RADS lexicon with a TRICKS images (ULTRAFAST), an abbreviated protocol (FAST) and all images (FULL protocol). Sensitivity, specificity, positive and negative predictive values, and accuracy were calculated for each protocol and compared with McNemar's test. RESULTS: For all readers, the combined FAST-ULTRAFAST protocol significantly improved the reading with a specificity of 83.3% and 70.8% in comparison with FAST protocol or FULL protocol, respectively, without change in sensitivity. By adding ULTRAFAST protocol to FAST protocol, readers 1 and 2 were able to correctly change the diagnosis in 22.9% (11/48) and 10.4% (5/48) of benign lesions, without missing any malignancy, respectively. Both interpretation and image acquisition times for combined FAST-ULTRAFAST protocol and FAST protocol were shorter compared to FULL protocol (p<0.001). CONCLUSION: Compared to FULL protocol, adding ULTRAFAST to FAST protocol improves specificity, mainly in correctly reclassifying benign masses and reducing interpretation and acquisition time, without decreasing sensitivity. PMID- 28987665 TI - Altered spontaneous brain activity pattern in cognitively normal young adults carrying mutations of APP, presenilin-1/2 and APOE epsilon4. AB - OBJECTIVE: To explore genetic effects of amyloid precursor protein (APP), presenilin-1/2 and apolipoprotein E (APOE) epsilon4 on brain structural and functional alterations in cognitively normal young adults. MATERIALS AND METHODS: Eighty healthy adults (mean age 24.0+/-2.5years; n=18, APP/presenilin-1/2 group; n=31, APOE epsilon4 group; n=31, control group [without above-mentioned gene mutation]) underwent high-resolution T1-weighted 3D anatomical imaging, resting state functional MR imaging and neuropsychological assessments. We used voxel based morphometry and regional homogeneity (ReHo) algorithms to investigate brain structural and functional changes among three groups, and performed correlation analyses between the brain regions with statistically significant difference and neuropsychological results. RESULTS: No brain structural changes were found, however, ReHo values were increased in right parietal-frontal lobes in APOE epsilon4 group, and decreased in the left middle temporal gyrus in APP/presenilin 1/2 group compared with controls (all P<0.05). Compared with APOE epsilon4 group, decreased ReHo values of bilateral temporal lobes were shown in APP/presenilin 1/2 group (P<0.05). ReHo values of right superior frontal gyrus in APOE epsilon4 group positively correlated with neuropsychological tests scores(P<0.05). CONCLUSION: Cognitively normal young adults carrying APOE epsilon4 or APP/presenilin-1/2 had different spontaneous brain activity patterns without cerebral structural differences. PMID- 28987666 TI - A comparative analysis of dual-phase dual-energy CT and FDG-PET/CT for the prediction of histopathological invasiveness of non-small cell lung cancer. AB - PURPOSE: To compare dual-phase dual-energy CT (DE-CT) with FDG-PET/CT for predicting histopathological locoregional invasiveness of non-small cell lung cancers (NSCLCs). MATERIALS AND METHODS: We selected 63 consecutive patients with NSCLC lesions (37 males, 26 females; age range, 44-85 years; mean age, 69 years) who were evaluated preoperatively by both DE-CT and PET/CT at our institution. Postoperative microscopic invasiveness (lymphatic permeation, vascular invasion, and/or pleural involvement) was reviewed, and we defined locoregionally invasive tumors as those that had at least one positive finding of microscopic invasiveness. DE-CT scanning in the arterial and delayed phases was performed after injection of iodinated contrast media using 140-kVp and 80-kVp tube voltages. Three-dimensional iodine-related attenuation of primary tumors in the arterial and delayed phases was quantified automatically using "syngo Dual Energy Lung Nodules" application software, and the ratio of arterial phase to delayed phase enhancement (A/D ratio) was calculated. The A/D ratio and SUVmax on PET/CT were evaluated with respect to postoperative invasiveness by univariate logistic regression analysis. RESULTS: The A/D ratio was significantly correlated with lymphatic permeation, vascular invasion, and pleural involvement (p=0.011, p=0.021, and p=0.010, respectively). In contrast, the SUVmax was significantly correlated with pleural involvement (p=0.020) but not with lymphatic permeation or vascular invasion (p=0.088 and p=0.100, respectively). In the subgroup of patients with lesion diameters <=2cm, the A/D ratio was significantly correlated with locoregional invasiveness (p=0.040), while the SUVmax was not (p=0.121). CONCLUSION: For the prediction of microscopic invasiveness of NSCLCs, the diagnostic performance of dual-phase DE-CT may be comparable to that of FDG PET/CT. PMID- 28987667 TI - Shear wave elastography findings of de Quervain tenosynovitis. AB - OBJECTIVE: Our aim was to evaluate the feasibility of using shear wave elastography (SWE) to assess first extensor compartment tendons rigidity and its alterations with tenosynovitis. MATERIALS AND METHODS: We performed B-mode ultrasound and SWE to total number of 80 participants. All participants were evaluated clinically to call the diagnosis of de Quervain tenosynovitis or to rule out the diagnosis. We composed 2 groups. Group 1 included 40 healthy volunteers (33 females and 7 male participants with ages ranging from 24 to 60 years, median age was 37.5 years) and group 2 had 40 de Quervain patients (32 females and 8 male patients with ages ranging from 25 to 51 years, median age was 34 years). SWE measurements were repeated 3 times and arithmetic average was used for the final SWE value. RESULTS: The median SWE value of healthy group (group 1) was 72kPa and the de Quervain patient group (group 2) was 29kPa. Two groups demonstrated statistically significant difference (p<0.001). The ROC curve analysis was performed and the SWE value of 40.5kPA was calculated as a cut-off value for the diagnosis of de Quervain tenosynovitis with 95% specificity and 85% sensitivity. CONCLUSION: SWE modality can provide useful data regarding de Quervain tenosynovitis. PMID- 28987668 TI - Abnormal brain function in neuromyelitis optica: A fMRI investigation of mPASAT. AB - PURPOSE: Cognitive impairment with the Neuromyelitis Optica (NMO) patients is debated. The present study is to study patterns of brain activation in NMO patients during a pair of task-related fMRI. MATERIALS AND METHODS: We studied 20 patients with NMO and 20 control subjects matched for age, gender, education and handedness. All patients with NMO met the 2006 Wingerchuk diagnostic criteria. The fMRI paradigm included an auditory attention monitoring task and a modified version of the Paced Auditory Serial Addition Task (mPASAT). Both tasks were temporally and spatially balanced, with the exception of task difficulty. RESULTS: In mPASAT, Activation regions in control subjects included bilateral superior temporal gyri (BA22), left inferior frontal gyrus (BA45), bilateral inferior parietal lobule (BA7), left cingulate gyrus (BA32), left insula (BA13), and cerebellum. Activation regions in NMO patients included bilateral superior temporal gyri (BA22), left inferior frontal gyrus (BA9), right cingulate gyrus (BA32), right inferior parietal gyrus (BA40), left insula (BA13) and cerebellum. Some dispersed cognition related regions are greater in the patients. CONCLUSIONS: The present study showed altered cerebral activation during mPASAT in patients with NMO relative to healthy controls. These results are speculated to provide further evidence for brain plasticity in patients with NMO. PMID- 28987669 TI - Histogram analysis of diffusion kurtosis imaging estimates for in vivo assessment of 2016 WHO glioma grades: A cross-sectional observational study. AB - PURPOSE: To assess the diagnostic performance of histogram analysis of diffusion kurtosis imaging (DKI) maps for in vivo assessment of the 2016 World Health Organization Classification of Tumors of the Central Nervous System (2016 CNS WHO) integrated glioma grades. MATERIALS AND METHODS: Seventy-seven patients with histopathologically-confirmed glioma who provided written informed consent were retrospectively assessed between 01/2014 and 03/2017 from a prospective trial approved by the local institutional review board. Ten histogram parameters of mean kurtosis (MK) and mean diffusivity (MD) metrics from DKI were independently assessed by two blinded physicians from a volume of interest around the entire solid tumor. One-way ANOVA was used to compare MK and MD histogram parameter values between 2016 CNS WHO-based tumor grades. Receiver operating characteristic analysis was performed on MK and MD histogram parameters for significant results. RESULTS: The 25th, 50th, 75th, and 90th percentiles of MK and average MK showed significant differences between IDH1/2wild-type gliomas, IDH1/2mutated gliomas, and oligodendrogliomas with chromosome 1p/19q loss of heterozygosity and IDH1/2mutation (p<0.001). The 50th, 75th, and 90th percentiles showed a slightly higher diagnostic performance (area under the curve (AUC) range; 0.868-0.991) than average MK (AUC range; 0.855-0.988) in classifying glioma according to the integrated approach of 2016 CNS WHO. CONCLUSIONS: Histogram analysis of DKI can stratify gliomas according to the integrated approach of 2016 CNS WHO. The 50th (median), 75th, and the 90th percentiles showed the highest diagnostic performance. However, the average MK is also robust and feasible in routine clinical practice. PMID- 28987670 TI - Image quality of virtual monochromatic images obtained using 320-detector row CT: A phantom study evaluating the effects of iterative reconstruction and body size. AB - OBJECTIVES: To compare the image quality between virtual monochromatic spectral (VMS) images obtained using 320-row detector CT and polychromatic 120-kVp images reconstructed with or without iterative reconstruction using various phantom sizes. MATERIALS AND METHODS: Torso phantoms simulating three patient sizes and containing four syringes filled with water or different contrast media (5, 10, 15mgI/mL15mgI/ml) were used. The phantoms were scanned using dual-energy (80/135 kVp) and single-energy (120-kVp) protocols at different settings (20mGy, 12mGy, and 6mGy). VMS images were generated at 1-keV intervals (range, 35-135keV). Both the VMS images and the single-energy 120-kVp images were reconstructed using filtered back projection (FBP) and adaptive iterative dose reduction 3D (AIDR 3D). The signal-to-noise ratio (SNR), and the contrast-to-noise ratio (CNR) were assessed. RESULTS: Using FBP reconstruction, the SNR and CNR of the VMS images were lower than or similar to those of the 120-kVp images for most dose settings. Using AIDR-3D reconstruction, however, the 70-keV VMS images had higher SNRs and CNRs than the 120-kVp images at most settings. CONCLUSIONS: The image quality of VMS images with FBP reconstruction tended to be lower than that of the 120-kVp images. With the use of AIDR-3D, however, approximately 70-keV VMS images had a higher image quality than the 120-kVp images. PMID- 28987671 TI - Dual energy spectral CT imaging for the evaluation of small hepatocellular carcinoma microvascular invasion. AB - OBJECTIVE: To study the clinical value of dual-energy spectral CT in the quantitative assessment of microvascular invasion of small hepatocellular carcinoma. METHODS: This study was approved by our ethics committee. 50 patients with small hepatocellular carcinoma who underwent contrast enhanced spectral CT in arterial phase (AP) and portal venous phase (VP) were enrolled. Tumour CT value and iodine concentration (IC) were measured from spectral CT images. The slope of spectral curve, normalized iodine concentration (NIC, to abdominal aorta) and ratio of IC difference between AP and VP (RICAP-VP: [RICAP-VP=(ICAP ICVP)/ICAP]) were calculated. Tumours were identified as either with or without microvascular invasion based on pathological results. Measurements were statistically compared using independent samples t test. The receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic performance of tumours microvascular invasion assessment. The 70keV images were used to simulate the results of conventional CT scans for comparison. RESULTS: 56 small hepatocellular carcinomas were detected with 37 lesions (Group A) with microvascular invasion and 19 (Group B) without. There were significant differences in IC, NIC and slope in AP and RICAP-VP between Group A (2.48+/ 0.70mg/ml, 0.23+/-0.05, 3.39+/-1.01 and 0.28+/-0.16) and Group B (1.65+/ 0.47mg/ml, 0.15+/-0.05, 2.22+/-0.64 and 0.03+/-0.24) (all p<0.05). Using 0.188 as the threshold for NIC, one could obtain an area-under-curve (AUC) of 0.87 in ROC to differentiate between tumours with and without microvascular invasion. AUC was 0.71 with CT value at 70keV and improved to 0.81 at 40keV. CONCLUSION: Dual energy Spectral CT provides additional quantitative parameters than conventional CT to improve the differentiation between small hepatocellular carcinoma with and without microvascular invasion. CLINICAL APPLICATION/RELEVANCE: Quantitative iodine concentration measurement in spectral CT may be used to provide a new method to improve the evaluation for small hepatocellular carcinoma microvascular invasion. PMID- 28987672 TI - Volume fractions of DCE-MRI parameter as early predictor of histologic response in soft tissue sarcoma: A feasibility study. AB - OBJECTIVE: To find early predictors of histologic response in soft tissue sarcoma through volume transfer constant (Ktrans) analysis based on dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). MATERIALS AND METHODS: 11 Patients with soft tissue sarcoma of the lower extremity that underwent preoperative chemoradiotherapy followed by limb salvage surgery were included in this retrospective study. For each patient, DCE-MRI data sets were collected before and two weeks after therapy initiation, and histologic tumor cell necrosis rate (TCNR) was reported at surgery. The DCE-MRI volumes were aligned by registration. Then, the aligned volumes were used to obtain the Ktrans variation map. Accordingly, three sub-volumes (with increased, decreased or unchanged Ktrans) were defined and identified, and fractions of the sub-volumes, denoted as F+, F- and F0, respectively, were calculated. The predictive ability of volume fractions was determined by using area under a receiver operating characteristic curve (AUC). Linear regression analysis was performed to investigate the relationship between TCNR and volume fractions. In addition, the Ktrans values of the sub volumes were compared. RESULTS: The AUC for F- (0.896) and F0 (0.833) were larger than that for change of tumor longest diameter DeltaD (0.625) and the change of mean KtransDeltaKtrans- (0.792). Moreover, the regression results indicated that TCNR was directly proportional to F0 (R2=0.75, P=0.0003), while it was inversely proportional to F- (R2=0.77, P=0.0002). However, TCNR had relatively weak linear relationship with DeltaKtrans- (R2=0.64, P=0.0018). Additionally, TCNR did not have linear relationship with DD (R2=0.16, P=0.1246). CONCLUSION: The volume fraction F- and F0 have potential as early predictors of soft tissue sarcoma histologic response. PMID- 28987674 TI - Accuracy of MR neurography in the diagnosis of brachial plexopathy. AB - OBJECTIVE: To assess the accuracy of MR neurography (MRN) for the diagnosis for brachial plexopathy. MATERIALS AND METHODS: Forty-three 43 consecutive cases or MRN with electrodiagnostic study correlation were reviewed independently by 2 readers. Established diagnostic criteria were employed: increased signal intensity, enlargement, loss of fascicular pattern, perineural edema and enhancement after administration of gadolinium contrast. An additional 37 cases without electrodiagnostic correlation were included in a second portion of the study, which evaluated interobserver variability. RESULTS: The sensitivity of MRN ranged from 41.2% to 70.6%. Specificity was 97.7% to 100%. There was good interobserver agreement, with kappa value of 0.658. Odds ratio for agreement between observers at 3T vs. 1.5T was 1.30. CONCLUSIONS: MRN of the brachial plexus showed only moderate sensitivity to brachial neuritis. Interobserver agreement was slightly higher at 3T than at 1.5T. MRN can be helpful in confirming an abnormal brachial plexus, but a normal MRN appearance of the plexus should not negate a clinical diagnosis. PMID- 28987673 TI - Paraduodenal pancreatitis as a mimicker of pancreatic adenocarcinoma: MRI evaluation. AB - PURPOSE: To evaluate the MRI features of paraduodenal pancreatitis (PDP) and to define useful signs to differentiate PDP from pancreatic ductal adenocarcinoma (PDAC). MATERIAL AND METHODS: We reviewed the MRI scans of 56 patients, 28 affected by PDP and 28 by PDAC, all pathologically proven. The following parameters were evaluated: signal intensity of the lesion on T1-, T2-WI, DWI (b800) and after contrast medium administration; presence of cysts; dilation of common hepatic duct and main pancreatic duct; focal thickening of the second portion of the duodenum; maximum diameter and volume of the lesion. RESULTS: Both PDPs and PDACs were more frequently hypointense on T1-WI, iso-hyperintense on T2 WI, hypointense in the pancreatic phase and iso-hypointense in the venous phase (p>0.05); in the delayed phase most PDP were hyperintense (p=0.0031); on DWI 71.4% PDPs were isointense and all PDACs were hyperintense (p=0.0041). Cystic components were present in 85.7% PDPs (p=0.0011); double duct sign was present in 50% PDACs (p=0.0048); focal thickening of the duodenum was depicted in 89.3 PDPs (p=0.0012). PDPs were larger than PDACs (p=0.0003). CONCLUSION: The most suggestive signs of PDP are: signal hyperintensity in the delayed phase, isointensity on DWI, presence of cysts, focal thickening of the duodenum and large size of the lesion. PMID- 28987675 TI - Influence of spectral detector CT based monoenergetic images on the computer aided detection of pulmonary artery embolism. AB - OBJECTIVE: To evaluate the influence of monoenergetic reconstructions using a spectral detector CT (SDCT) on the computer aided detection (CAD) of pulmonary artery embolism (PAE) on CT pulmonary angiography (CTPA) and CT in venous contrast phase (CTV). MATERIAL AND METHODS: A retrospective data base search identified 15 patients with CTPA and 18 patients with CTV and diagnosis of PAE. For these patients, monoenergetic (monoE) images at different energy levels or with a fixed attenuation in the pulmonary artery were generated and independently analyzed using a commercially available computer aided detection (CAD) tool. Attenuation in the pulmonary artery and in the embolus was measured. RESULTS: For CTPA and CTV, in monoenergetic images the difference in attenuation between vessel and embolus was significantly higher than in conventional images. In CTPA the detection rate was highest in the >500 HU monoE images with 67,9% detected emboli and 93,3% of patients correctly identified as having PAE. At the same time the false positive rate could be significantly reduced by using monoE images compared to conventional images. Detection rates for CTV were lower than in CTPA but were raised significantly by monoE reconstructions. CONCLUSIONS: The combination of SDCT and CAD improves the diagnostic accuracy of CAD and enables CAD interpretation of CTV. PMID- 28987676 TI - Value of diffusion tensor imaging in differentiating malignant from benign parotid gland tumors. AB - PURPOSE: To evaluate whether diffusion tensor imaging (DTI) can be used to differentiate malignant parotid gland tumors from the benign ones. MATERIALS AND METHODS: The study population comprised 59 parotid gland tumors (24 Warthin's tumors, 19 pleomorphic adenomas, seven other benign tumors, and nine malignant tumors). Single-shot echo-planar DTI was performed with motion-probing gradients along 30 noncollinear directions (b=1000s/mm2) at 3.0T. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values for benign and malignant tumors were compared using the Mann-Whitney U test. Receiver-operating characteristic (ROC) curve analysis was performed to assess the ability of the ADC and FA values to differentiate malignant tumors from the benign ones. RESULTS: ADC values showed no significant difference between malignant (0.93+/ 0.21*10-3mm2/s) and benign tumors (1.19+/-0.50*10-3mm2/s) (p=0.225). FA values of malignant tumors were significantly higher than those of benign tumors (0.26+/ 0.06 vs. 0.17+/-0.05, p<0.001). The area under the ROC curve of FA was significantly greater than that under the curve of ADC (0.884 vs. 0.628, p=0.010). CONCLUSIONS: DTI, particularly FA, can help differentiate malignant parotid gland tumors from the benign ones. PMID- 28987677 TI - Quantification accuracy of neuro-oncology PET data as a function of emission scan duration in PET/MR compared to PET/CT. AB - OBJECTIVES: To evaluate and compare the effect of reduced acquisition time, as a surrogate of injected activity, on the PET quantification accuracy in PET/CT and PET/MR imaging. METHODS: Twenty min 18F-FDG phantom measurements and 10min 18F FET brain scans were acquired in a Biograph-True-Point-True-View PET/CT (n=8) and a Biograph mMR PET/MR (n=16). Listmode data were repeatedly split into frames of 1min to 10min length and reconstructed using two different reconstruction settings of a 3D-OSEM algorithm: with post-filtering ("OSEM"), and without post filtering but with resolution recovery ("PSF"). Recovery coefficients (RCmax, RCA50) and standard uptake values (SUVmax, SUVA50) were evaluated. RESULTS: RCmax (phantom) and SUVmax (patients) increased significantly when reducing the frame duration. Significantly lower deviations were observed for RCA50 and SUVA50, respectively, making them more appropriate to compare PET studies at different number of counts. No statistical significant differences were observed when using post-filtering and reducing the frame time to 4min (RCA50, reference 20min, phantom) and to 3min (SUVA50, reference 10min, patients). CONCLUSIONS: For hybrid aminoacid brain imaging, frame duration (or injected activity) can potentially be reduced to 30% of the standard used in clinical routine without significant changes on the quantification accuracy of the PET images if adequate reconstruction settings and quantitative measures are used. Frame times below 4min in the NEMA phantom are not advisable to obtain quantitative and reproducible measures. PMID- 28987678 TI - Magnetic resonance diffusion tensor imaging of the testis: Preliminary observations. AB - INTRODUCTION: To evaluate the feasibility of testis diffusion tensor imaging (DTI), to determine normative apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values and to assess the efficacy of DTI in characterizing testicular pathology. MATERIALS AND METHODS: Fifty-six men underwent MRI of the scrotum, including DTI. Parametric and non-parametric statistical tests were used to compare the ADC and FA between the cranial, middle and lower thirds of normal testis and between the bilateral testicular thirds. Comparison between the ADC and FA of normal testis, malignant and benign testicular lesions was performed. RESULTS: No significant differences of the ADC and FA in normal testis between the cranial, middle and lower thirds and between the bilateral testicular thirds were found. ADC was significantly lower in malignancies compared to normal testis (P=0.006) and benign testicular lesions (P=0.006). FA was significantly higher both in malignancies (P=0.001) and benign lesions (P<0.001) compared to normal testis. FA in malignancies did not differ from FA in benign lesions (P=0.221) CONCLUSIONS: This study shows the feasibility of testis DTI. Both ADC and FA significantly differ between testicular lesions and normal testis, although FA did not show an incremental diagnostic value compared to ADC in lesion differentiation. PMID- 28987679 TI - Impact of MRI on high grade Ductal Carcinoma Insitu (HG DCIS) management, are we using the full scope of MRI? AB - INTRODUCTION: Preoperative assessment of pure Ductal Carcinoma Insitu (DCIS) is essential in the surgical planning. The role of Magnetic resonance imaging (MRI) has long been debated. The impact of MRI on the management of High Grade (HG) DCIS was assessed, whether it accurately captures the true size of this entity in comparison to conventional imaging, and, if MRI use would reduce the number of re excision surgery. METHOD: Ninety-one consecutive patients with HG DCIS, who were identified from a prospectively collected data at Kettering General Hospital between April 2011 and December 2015. All patients had preoperative MRI scan in addition to the standard breast imaging. This was compared to a control group of consecutive patients (n=52) which was obtained from a period just before 2011. Impact on surgical planning and number of surgeries for each patient was compared. The size of HG DCIS estimated by MRI was compared to the final histological size. Secondary outcomes included change of initial surgical plan and detection of occult contralateral breast cancer. RESULTS: MRI group had 91 patients with median age of 63. Seventy percent of which presented through the screening program. The overall sensitivity of MRI to detect HG DCIS was 77% (70/91) with a false negative rate FNR of 23% (21/91). Therefore, 70 patients only were included in the data analysis. The control group included 52 screening patients with comparable baseline characteristics. Re-excision (or completion mastectomy) rates were higher in the control group 26% compared to 8% in the MRI group (P-value 0.012). MRI use correctly converted the initial plan of breast conservation to mastectomy in 9 patients (13%). Five patients had additional ipsilateral malignant features (7%).Occult contra lateral disease, was diagnosed in 2 patients (3%). CONCLUSION: This study suggests that MRI could be an important tool in reducing the re-excision rates in the surgical management of HG DCIS. Although still controversial, selective MRI imaging can be useful in the preoperative diagnosis and evaluation of HG DCIS. Case by case discussion at MDT is crucial. Wider adaptation of MRI when indicated in the assessment of breast lesions with proper correlation to histology postoperatively is a key in improving our MRI interpretation skills, helping us to exploit the full scope of this useful tool. PMID- 28987681 TI - The Evans' Index revisited: New cut-off levels for use in radiological assessment of ventricular enlargement in the elderly. AB - BACKGROUND AND PURPOSE: Assessment of ventricular enlargement is subjective and based on the radiologist's experience. Linear indices, such as the Evans Index (EI), have been proposed as markers of ventricular volume with an EI>=0.3 indicating pathologic ventricular enlargement in any subject. However, normal range for EI measured on magnetic resonance imaging (MRI) scans are lacking in healthy elderly according to age and sex. We propose new age and sex specific cut off values for ventricular enlargement in the elderly population. MATERIALS AND METHODS: 534 participants (53% women) aged 65-84 years; 226 patients with Alzheimer's disease (AD), and 308 healthy elderly controls (CTR) from the AddNeuroMed and ADNI studies were included. The cut-off for pathological ventricular enlargement was estimated from healthy elderly categorized into age groups of 5 years range and defined as EI 97,5 percentile (mean+2SD). Cut-off values were tested on patients with Alzheimer's disease and a small sample of patients with probable idiopathic normal pressure hydrocephalus (iNPH) to assess the sensitivity. RESULTS: The range of the EI in healthy elderly is wide and 29% of the CTR had an EI of 0.3 or greater. The EI increases with age in both CTR and AD, and the overall EI for women were lower than for men (p<0.001). New EI cut off values for male/female: 65-69 years 0.34/0.32, 70-74 years 0.36/0.33, 75-79 years 0.37/0.34 and 80-84 years 0.37/0.36. When applying the proposed cut-offs for EI in men and women aged 65-84, they differentiated between iNPH and CTR with a sensitivity of 80% and for different age and sex categories of AD and CTR with a sensitivity and specificity of 0-27% and 91-98%, respectively. CONCLUSION: The range of the EI measurements in healthy elderly is wide, and a cut-off value of 0.3 cannot be used to differentiate between normal and enlarged ventricles in individual cases. The proposed EI thresholds from the present study show good sensitivity for the iNPH diagnosis. PMID- 28987680 TI - Diagnosing acute pancreatitis-Clinical and radiological characterisation of patients without threefold increase of serum lipase. AB - OBJECTIVES: Diagnosing acute pancreatitis (AP) may be challenging in patients with acute abdominal pain but missing threefold increased serum lipase levels (Lip-). This studyaims both to characterize these patients using clinical, radiological and mortality data, and to assess the group of patients who need contrast-enhanced computed tomography (CECT). METHODS: In this retrospective, IRB approved study 234 consecutive patients with AP were investigated. Inclusion criteria were single (SAP) and recurrent attacks (RAP) of AP and CECT >=72h after onset of symptoms. Severity of AP was assessed by C-reactive protein at 48h after hospital admission and using 3 CT-based scores (CTSI, mCTSI, EPIC) by 2 observers. Mortality rates from pancreatic and non-pancreatic causes were noted with regard to lipase increase. Results were compared with paired t-test and Wilcoxon signed-rank test. RESULTS: 64/234 (27%) patients belonged to Lip- group and 170/234 (73%) patients were allocated to Lip+ group. Significantly more male patients (78% in Lip- vs. 63% in Lip+, p<0.05) with RAP (63% in Lip- vs. 21% in Lip+, p<0.001) were observed in the Lip- group. EPIC was significantly lower in Lip- group compared to Lip+ group (3(IQR 2-5) vs. 2(IQR 1-3), p<0.001). Mortality from pancreatic and non-pancreatic causes was comparable in Lip- and Lip+ group (pancreatic causes: 9% vs. 6%, p=0.60; nonpancreatic causes: 8% vs. 5%, p=0.58). CONCLUSIONS: 27% of all patients with AP presented without threefold increase of lipase levels. Thus, they would be underdiagnosed without confirming CECT, which revealed significantly lower counts of pleural effusions and ascites. Male patients with RAP were found significantly more often among the Lip- group. Hence, they would benefit the most from CECT for diagnosing AP. PMID- 28987682 TI - MR diffusion kurtosis imaging predicts malignant potential and the histological type of meningioma. AB - PURPOSE: To explore the value of Diffusion kurtosis imaging (DKI) metrics in the differential diagnosis of meningioma. METHODS: For this study, we retrospectively enrolled 35 patients of cerebral meningioma with DKI which included axial diffusion coefficient (AD), radial diffusion coefficient (RD), mean diffusion coefficient (MD), fractional anisotropy (FA), axial kurtosis (AK), radial kurtosis (RK) and mean kurtosis (MK). All of these metrics were normalized according to contralateral normal-appearing white matter (NAWMc). Patients were divided into two groups (benign and malignant meningioma) and were further analyzed using the independent sample t-test and receiver operating characteristic (ROC) curve. A one-way ANOVA analysis was used to analyze four groups divided according to pathological subtypes. RESULTS: The metrics of AD, normalized AD, normalized MD, MK and normalized MK showed a significant difference between benign and malignant group, and MK showed relatively higher diagnostic ability with its cut-off value, area under the curve (AUC), sensitivity and specificity of 0.875, 0.780, 70% and 89%, respectively. The metrics of normalized MD, RD and normalized RD, FA and normalized FA, AK and normalized AK, and RK showed significant difference among four subtypes. MK and RK in meningioma were found to correlate positively with the Ki-67 labeling index (Ki-67 LI). CONCLUSIONS: DKI metrics may be used to differentiate benign from malignant meningioma, and also to distinguish some histological subtypes of meningioma. Moreover, DKI metrics may potentially reflect cellular proliferation. PMID- 28987683 TI - Influence of fissure integrity on quantitative CT and emphysema distribution in emphysema-type COPD using a dedicated COPD software. AB - OBJECTIVES: Fissure integrity (FI) plays a key role in selecting patients for interventional emphysema therapy. We investigated its interference with automated lobar segmentation in quantitative computed tomography (CT) and emphysema distribution. METHODS: CT was available for 50 patients with chronic obstructive pulmonary disease (COPD). Lobe segmentation was performed fully automated by software and corrected manually. FI was evaluated visually using a %-scale. The influence of FI on emphysema ratio (ER=percentage of lung volume with density values<-950 HU), mean lung density (MLD), emphysema and total volume of adjacent lobes was analyzed. Lobe-based results were compared with respect to FI. RESULTS: Differences in ER in adjacent lobes for complete vs. incomplete fissures were 12.4% for the right horizontal, 0.2% and 3% for the right oblique and 4.4% for the left oblique fissure (all p>0.05). Results for emphysema comparing automated vs. manually corrected segmentation exceeded clinically acceptable values, but were not significantly affected by FI (p>0.05). The widest limits of agreement for ER and MLD were noted in the right middle lobe ([-14, 17.4%], [-22.4, 32.4 Hounsfield Units]). CONCLUSIONS: Automated lobe segmentation and emphysema distribution are not significantly affected by FI. Manual correction of automated lobar segmentation is still recommended in severe emphysema. PMID- 28987684 TI - Material density iodine images in dual-energy CT: Detection and characterization of hypervascular liver lesions compared to magnetic resonance imaging. AB - PURPOSE: To determine the diagnostic potential of Material Density (MD) iodine images in dual-energy CT (DECT) for the detection and characterization of hypervascular liver lesions compared to monenergetic 65keV images, using MRI as the standard. MATERIALS AND METHODS: The study complied with HIPAA guidelines and was approved by the institutional review board. Fifty-two patients (36 men, 16 women; age range, 29-87 years) with 236 hypervascular liver lesions (benign, n=31; malignant, n=205; mean diameter, 29.4mm; range: 6-90.6mm) were included. All of them underwent both contrast-enhanced single-source DECT and contrast enhanced abdominal MRI within three months. Late arterial phase CT imaging was performed with dual energies of 140 and 80kVp. Protocol A showed monoenergetic 65keV images, and protocol B presented MD-iodine images. Three radiologists qualitatively evaluated randomized images, and lesion detection, characterization, and reader confidence were recorded. Liver-to-lesion ratio (LLR) and contrast-to-noise ratio (CNR) were assessed on protocol A, protocol B, and MRI. Paired t-tests were used to compare LLR, CNR, and the number of detected lesions. RESULTS: LLR was significantly increased in protocol B (2.8+/-2.33) compared to protocol A (0.77+/-0.55) and MRI (0.61+/-0.66). CNR was significantly higher in protocol B (0.08+/-0.04) compared to protocol A (0.01+/-0.01) and MRI (0.01+/-0.01). All three observers correctly identified more liver lesions using protocol B vs protocol A: 83.13% vs 63.64%, 84.57% vs 68.09%, and 79.37% vs 65.52%. There was no significant difference between the three observers in classification of a lesion as benign or malignant. However, higher diagnostic confidence was reported more frequently by the experienced radiologist when using protocol B vs protocol A (84.6% vs 75%). CONCLUSION: MD-iodine images in DECT help to increase the conspicuity and detection of hypervascular liver lesions. PMID- 28987685 TI - Sub-differentiating equivocal PI-RADS-3 lesions in multiparametric magnetic resonance imaging of the prostate to improve cancer detection. AB - PURPOSE: To evaluate sub-differentiation of PI-RADS-3 prostate lesions using pre defined T2- and diffusion-weighted (DWI) MRI criteria, to aid the biopsy decision process. METHODS: 143 patients with PIRADS-3 index lesions on MRI underwent targeted transperineal-MR/US fusion biopsy. Radiologists with 2 and 7-years experience performed blinded retrospective second-reads using set criteria and assigned biopsy recommendations. Inter-reader agreement, Gleason score (GS), positive (PPV) predictive values (+/-95% confidence intervals) were calculated and compared by Fisher's exact test with Bonferroni-Hom correction. RESULTS: 43% (61/143) patients had GS 6-10 and 21% (30/143) GS>=3+4 cancer. For peripheral zone lesions, significant differences in any cancer detection were found for shape (0.26+/-0.13 geographical vs. 0.69+/-0.23 rounded; p=0.0055) and ADC (mild 0.21+/-0.12 vs marked 0.81+/-0.19; p=0.0001). For transition zone, significantly increased cancer detection was shown for location (anterior 0.63+/-0.15 vs. mid/posterior 0.31+/-0.14; p=0.0048), border (pseudo-capsule 0.32+/-0.14 vs. ill defined 0.61+/-0.15; p=0.0092), and ADC (mild 0.35+/-0.12 vs marked restriction 0.68+/-0.17; p=0.0057). Biopsy recommendations had 62% inter-reader agreement (89/143). Experienced reader PPVs were significantly higher for any cancer with "biopsy-recommended" 0.61+/-0.11 vs. "no biopsy" 0.21+/-0.10 (p=0.0001), and for GS 7-10 cancers: 0.32+/-0.10 vs. 0.08+/-0.07, respectively (p=0.0003). CONCLUSION: Identification of certain objective imaging criteria as well as a subjective biopsy recommendation from an experienced radiologist can help to increase the predictive value of equivocal prostate lesions and inform the decision making process of whether or not to biopsy. PMID- 28987686 TI - Can the "pine-needle sign" on computed tomography be used to differentiate pulmonary arteriovenous malformation from its mimics? Analysis based on dynamic contrast-enhanced chest computed tomography in adults. AB - OBJECTIVES/PURPOSE: To determine the diagnostic value of morphological features on computed tomography (CT) in the differentiation of pulmonary arteriovenous malformation (pAVM) and its mimics. MATERIALS AND METHODS: We retrospectively examined 59 consecutive patients (109 lesions) with initially suspected or occult pAVM who underwent contrast-enhanced chest CT from January 2006 to June 2016. All lesions were divided into two groups based on their diagnosis: AVM (n=93) and non AVM (n=16). The non-AVM group comprised patients with an anomalous unilateral single pulmonary vein and congenital pulmonary venous atresia. Two board certified radiologists reviewed the CT images and achieved consensus. Paired abnormal vessels were assessed with respect to their configuration, direction and continuity with the hilum, location, angle between them, and dilation ratio. RESULTS: All pAVM lesions had parallel, straight-running, paired abnormal vessels; most of the vessels ran through the identical segment. Conversely, in the non-AVM group, paired abnormal vessels did not run in parallel but detoured to the hilum through different segments from each other (i.e., the configuration, direction and continuity with the hilum and the location of the vessels were all significantly different between the two groups). The angle between the paired abnormal vessels was significantly narrower in the AVM group. The dilation ratio was not significantly different between the two groups. CONCLUSION: Morphological features can be useful in the differentiation of pAVM and its mimics without contrast-enhanced CT to directly visualize the connection between the abnormal and normal pulmonary vessels. Pulmonary AVMs characteristically had a narrow angle between the two vessels, appearing like a pair of pine-needle leaves. PMID- 28987687 TI - Incidental liver lesions seen on Breast MRI: When is additional imaging warranted? AB - PURPOSE: Incidental hepatic lesions identified on breast MR can be a diagnostic dilemma due to concern for liver metastases or other significant hepatic lesions. The purpose of this study was to identify the incidence and nature of liver lesions seen on breast MR, and determine if additional imaging is necessary. METHODS AND MATERIALS: Imaging reports of all breast MR examinations performed at our institution from January 1, 2010 to December 31, 2011 were reviewed to identify reports with hepatic abnormalities. Lesion characteristics, subsequent diagnosis, duration of follow up and additional imaging results (if performed) were all recorded. RESULTS: Of 1664 breast MRs, incidental hepatic lesions were seen in 207 studies (12.4%) in 169 patients. In 154 of 169 patients (91.1%) the lesions were characterized as T2 hyperintense and clearly as bright as adjacent fat on T2-weighted or localizer sequences. 0 of these 154 lesions were clinically significant at clinical or radiological follow-up. In the remaining 8.9% (15 of 169), lesions were characterized as not as bright as adjacent fat on T2 weighted or localizer imaging. In two cases, lesions were confirmed as incidental hepatic metastatic disease. CONCLUSION: 91.1% of incidental hepatic lesions were circumscribed, T2 hyperintense lesions and characterised as clearly as bright as adjacent fat on T2 weighted imaging at additional review. None of which were clinically significant at clinical or radiological follow-up. We advocate that circumscribed T2 hyperintense lesions which are clearly as bright as adjacent fat on T2 weighted imaging are of unlikely clinical significance and follow-up imaging should not be recommended, reducing the rate of additional imaging from 37.3% to 5.3%. PMID- 28987688 TI - Differentiation of hypointense nodules on gadoxetic acid-enhanced hepatobiliary phase MRI using T2 enhanced spin-echo imaging with the time-reversed gradient echo sequence: An initial experience. AB - PURPOSE: To optimize the flip angle (FA) of the T2 enhanced spin-echo imaging using the time reversed gradient echo (T2FFE) and evaluate its utility for differentiating hypointensity nodules in the hepatobiliary phase (HBP) of gadoxetic acid-enhanced (Gd-EOB) MRI. MATERIALS AND METHODS: First, FA optimization of the T2FFE in the HBP was investigated by comparing signal-to noise ratio (SNR) among different FAs using phantoms. The liver-to-muscle contrast ratios (CRLiver-Muscle) and image quality among three FAs (20 degrees , 50 degrees and 80 degrees ) were compared using images of 10 patients. Next, the utility of the T2FFE with an optimized FA for differentiating hypointensity nodules in the HBP was assessed by comparing the lesion-to-liver contrast ratio (CRLesion-Liver) among cysts, hemangiomas, hepatocellular carcinomas, and metastatic tumors in 32 patients. RESULTS: SNR increased as FA increased, but leveled off at FAs of 50 degrees and greater. The FA of 50 degrees showed significantly better image quality scores than that of 80 degrees (p<0.05). After employing an FA of 50 degrees , the CRLesion-Liver value indicated that the T2FFE depicted benign lesions as hyperintense and most malignant lesions as hypointense in relation with the liver parenchyma (p<0.05). CONCLUSION: The T2FFE in the HBP of Gd-EOB-MRI is useful for differentiating benign and malignant liver lesions. PMID- 28987689 TI - Pancreatic adenocarcinoma: A simple CT score for predicting margin-positive resection in patients with resectable disease. AB - BACKGROUND: Negative-margin status is a prognostic indicator for long-term survival following curative intent resection for pancreatic adenocarcinoma. Patients at increased risk for positive-margin resections may benefit from neoadjuvant chemotherapy prior to resection. METHODS: We retrospectively analyzed preoperative computed-tomography (CT) scans in 108 consecutive patients that underwent curative intent resection for a resectable pancreatic ductal adenocarcinoma from 2009 to 2016 in two academic hospitals. Two radiologists independently staged the tumor, including tumor location, size, and tumor-to superior mesenteric/portal vein (SMV/PV) contact. Uni and multivariate analysis were performed to identify independent predictors of an R1 resection. RESULTS: Twenty-nine patients had an R1 resection (26.9%). Tumor size, location, and presence of tumor-to-SMV/PV contact were significantly associated with an R1 resection. In multivariate analysis, the independent parameters associated with resection status were: tumor size (R2=9.7), and tumor location (neck R2=6.6; pancreaticoduodenal interface R2=4.4; uncinate process R2=4.1), but not tumor-to SMV/PV contact (R2=0.1, p=0.7). A simple CT score was built based on tumor size and location. Patients with an R0 resectability score >=3, i.e. patients with tumor size >=30mm (except when tumor location is at the pancreatico-duodenal interface) or patients with tumor size >=20mm AND tumor located in the uncinate process or neck, were at high-risk of an R1 resection (AUC, 0.82; sensitivity, 79%; specificity, 76%). This score also showed good diagnostic performances for predicting an R1 resection involving the medial resection margin only (AUC, 0.85). CONCLUSIONS: A simple score based on tumor location and size can accurately predict patients at high-risk of an R1 resection. PMID- 28987690 TI - Peri-aortic fluid after surgery on the ascending aorta: Worrisome indicator of complications or innocent postoperative finding? AB - OBJECTIVE: The Bentall procedure is associated with several complications often accompanied by accumulation of fluid around the aortic graft. CT is the imaging modality of choice to detect these complications. Since these early complications are, however, not easily distinguished from physiological postoperative changes, our aim was to compare the appearance and amount of peri-aortic fluid on early CT scans following Bentall procedures with either an uncomplicated or a complicated course and follow-up. METHODS: Ninety-four scans performed within 3 months of a Bentall procedure were retrospectively included. Patients were divided into either the uncomplicated or the complicated group based on occurrence of Bentall related complications or death up until 1-year after surgery. Diffuse fluid ("stranding") was distinguished from organized, more clearly delineated fluid collections such as haematomas, and was graded both subjectively and quantitatively. RESULTS: Forty-seven patients were assigned to each group. Stranding was found on most of the scans, both in the uncomplicated (7.7+/-3.9mm, range 0-17mm) and complicated (6.9+/-5.5mm, range 0-19mm) groups (p=0.32). There were, however, significantly more fluid collections (6 vs. 28; p <0.001), particularly haematomas (1 vs. 17; p<0.001), in the complicated group. When looking at isolated stranding, there was still no significant difference between the two groups (7.8+/-3.6mm vs. 9.2+/-3.7mm; p=0.22). CONCLUSION: Isolated stranding of up to 17mm is a common finding on postoperative CT within three months of a Bentall procedure, regardless of the occurrence of complications during the procedure or within a 1-year follow-up. Fluid collections are more worrisome indicators of complications that may require closer monitoring. PMID- 28987691 TI - Pharyngeal airspace of asthmatic individuals and those suffering from obstructive sleep apnea syndrome: Study by CBCT. AB - PURPOSE: The objective of the present study was to comparatively evaluate the oropharyngeal space of patients with obstructive sleep apnea syndrome (OSA) and asthma by means of Cone Beam Computed Tomography (CBCT) images. MATERIAL AND METHODS: The study included individuals with OSA and asthma (n=10), with OSA and without asthma (n=6), asthmatics without OSA (n=6) and healthy individuals (n=25). All patients were evaluated by a pneumologist and submitted to a nocturnal polysomnogram. Participants underwent CBCT examinations using an I CAT(r) device (Imaging Sciences International, Hatfield, PA, U.S.A.) and all images were exported to Dolphin Image 3D(r) software. Cephalometric measurements were taken, as well as measurements of length (C), volume (VOL), sagittal area (SA) and minimum cross-sectional area (MCA); an evaluation was made of the format and contour of the upper airway in three dimensions, with p<0.05 considered significant. RESULTS: In the results of the present study, a statistically significant difference was found between VOL, SA and MCA (p=0.011; p=0.009; p=0.010) with reduced elevated values among the OSA+Asthma, OSA, Asthma and Control groups. Significant differences were seen between the linear (AP), cross sectional (TR) and mean transverse area (TA) measurements in the group of patients with OSA and asthma as compared to the control group. In the control group, the greatest narrowing of the airway was observed either in the retroglossal or retropalatal area, while more patients in the experimental groups showed narrowing in the retropalatal area. CONCLUSION: The condition of OSA+asthma was associated with a substantial reduction in upper airway measurements in comparison to controls. PMID- 28987692 TI - Primary malignant tumours in the non-cirrhotic liver. AB - Intrahepatic chlangiocarcinomas (CCs), the second most common primary malignant liver tumours, usually occur in non-cirrhotic liver, and can be classified into three types based on gross morphology: mass-forming; periductal infiltrating; and intraductal growing. Among them, mass-forming intrahepatic CCs are the most common type and characterized by homogeneous mass with an irregular but well defined margin with peripheral enhancement on late arterial phase and delayed enhancement in central portion of tumours corresponding to the fibrous stroma. Several imaging features such as enhancement pattern and degree of diffusion restriction have been suggested as prognostic markers for mass-forming CCs. Hepatocellular carcinomas (HCCs) are the most common primary malignant liver tumors, and usually arise from the cirrhotic liver. However, approximately 20% of HCCs involve the non-cirrhotic liver (hereafter, non-cirrhotic HCC), and non cirrhotic HCCs are often detected at an advanced stage due to the lack of surveillance for patients with non-cirrhotic liver. Other primary malignant liver tumours other than CCs and HCCs including angiosarcoma, undifferentiated embryonal sarcoma are quite rare, and imaging diagnosis is often difficult. This review offers a brief overview of epidemiology, risk factors and imaging features of primary malignant tumours in non-cirrhotic liver. Understanding of radiologic appearance and predisposing clinical features as well as differentials of primary malignant tumour in non-cirrhotic liver can be helpful for radiologists to adequately assess these tumours, and subsequently to make optimal management plan. PMID- 28987693 TI - Association between non-hypervascular hypointense nodules on gadoxetic acid enhanced MRI and liver stiffness or hepatocellular carcinoma. AB - PURPOSE: To assess the association between non-hypervascular hypointense nodules (NHHNs) on gadoxetic acid-enhanced magnetic resonance imaging (MRI) and liver stiffness (LS) in patients with chronic liver disease, and analyzed their progression to overt hepatocellular carcinoma (HCC). METHODS: Between August 2012 and March 2016, a total of 714 consecutive patients who had undergone transient elastography for LS measurement and gadoxetic acid-enhanced MRI were investigated. The association between the presence of NHHNs on the hepatobiliary phase and LS, and the patient's HCC status [none, presence of treatment-naive HCC, or a history of previous HCC treatment] was assessed. In patients with these nodules, cumulative progression rates of nodules to overt HCC were compared with rates of new HCC development in other parts of the liver. RESULTS: The prevalence of NHHNs was 16.8% (120/714). The presence of these nodules was significantly associated with the log LS (Odds ratio [OR], 1.48, p=0.002) and hepatitis B virus infection (OR, 3.14, p=0.017), regardless of the patient's HCC status. The two year cumulative progression rate of overt HCC from corresponding nodules and rate of progression to HCC in other parts of the liver were 34.1% and 18.3%, respectively (p=0.071). CONCLUSION: The presence of NHHNs on gadoxetic acid enhanced MRI was associated with higher LS and hepatitis B virus infection. Furthermore, these lesions frequently progressed to overt HCC. PMID- 28987694 TI - On the effect of computed tomography resolution to distinguish between abdominal aortic aneurysm wall tissue and calcification: A proof of concept. AB - PURPOSE: The purpose of this study is to determine the optimal target CT spatial resolution for accurately imaging abdominal aortic aneurysm (AAA) wall characteristics, distinguishing between tissue and calcification components, for an accurate assessment of rupture risk. MATERIALS AND METHODS: Ruptured and non ruptured AAA-wall samples were acquired from eight patients undergoing open surgical aneurysm repair upon institutional review board approval and informed consent was obtained from all patients. Physical measurements of AAA-wall cross section were made using scanning electron microscopy. Samples were scanned using high resolution micro-CT scanning. A resolution range of 15.5-155MUm was used to quantify the influence of decreasing resolution on wall area measurements, in terms of tissue and calcification. A statistical comparison between the reference resolution (15.5MUm) and multi-detector CT resolution (744MUm) was also made. RESULTS: Electron microscopy examination of ruptured AAAs revealed extremely thin outer tissue structure <200MUm in radial distribution which is supporting the aneurysm wall along with large areas of adjacent medial calcifications far greater in area than the tissue layer. The spatial resolution of 155MUm is a significant predictor of the reference AAA-wall tissue and calcification area measurements (r=0.850; p<0.001; r=0.999; p<0.001 respectively). The tissue and calcification area at 155MUm is correct within 8.8%+/-1.86 and 26.13%+/-9.40 respectively with sensitivity of 87.17% when compared to the reference. CONCLUSION: The inclusion of AAA-wall measurements, through the use of high resolution-CT will elucidate the variations in AAA-wall tissue and calcification distributions across the wall which may help to leverage an improved assessment of AAA rupture risk. PMID- 28987695 TI - Primary benign liver lesions. AB - Benign focal liver lesions can origin from all kind of liver cells: hepatocytes, mesenchymal and cholangiocellular line. Their features at imaging may sometimes pose difficulties in differential diagnosis with malignant primary and secondary lesions. In particular, the use of MDCT and MRI with extracellular and hepatobiliary Contrast Agents may non invasively help in correct interpretation and definition of hepatocellular or mesenchymal and inflammatory nature, allowing to choose the best treatment option. The peculiarities of main benign liver lesions at US, CT and MRI are described, with special attention to differential diagnosis and diagnostic clues. PMID- 28987696 TI - Computed diffusion-weighted MR imaging for visualization of pancreatic adenocarcinoma: Comparison with acquired diffusion-weighted imaging. AB - OBJECTIVE: To assess the feasibility of computed diffusion-weighted imaging (cDWI) in comparison with directly acquired DWI for visualizing pancreatic adenocarcinomas. MATERIALS AND METHODS: Patients with pancreatic adenocarcinoma underwent DWI at b-values of 0, 1000 (DWI1000), 1500 (DWI1500) and 2000 (DWI2000) s/mm2. From DWIs at b-values of 0 and 1000s/mm2, we generated cDWIs at b-values of 1500 (cDWI1500) and 2000 (cDWI2000) s/mm2. DWI findings of pancreatic adenocarcinomas (clear hyperintensity; hyperintensity with an unclear distal border; and isointensity), the image quality and the tumor to pancreas contrast ratio (CR) were compared between directly acquired DWI and cDWI. RESULTS: Among the 63 included patients, clear hyperintense tumors were seen in 35 on DWI1000, 50 on DWI1500, 50 on cDWI1500, 53 on DWI2000 and 44 on cDWI2000. Incidence of clear hyperintense tumors was significantly higher on cDWI1500 than on DWI1000 (P=0.013). There was no significant difference in the incidence of clear hyperintense tumors between DWI1500 and cDWI1500 (P>0.999), but a lower incidence was seen on cDWI2000 than on DWI2000 (P=0.028). Image quality was lower on cDWI than on DWI at b-values of 1500 (P=0.002) and 2000s/mm2 (P<0.001). The tumor to distal pancreas CR was significantly higher on cDWI2000 than on cDWI1500 (P<0.001), and on cDWI1500 than on DWI1000 (P<0.001). The cDWI showed a significantly higher tumor to distal pancreas CR than DWI at b-values of 1500 (P=0.004) and 2000s/mm2 (P<0.001). CONCLUSIONS: cDWI1500 generated from b-values of 0 and 1000s/mm2 should be considered more effective than DWI1000 and at least as effective as DWI1500. PMID- 28987697 TI - Perfusion CT - A novel quantitative and qualitative imaging biomarker in gastric cancer. AB - OBJECTIVES: The aim of this research was to examine whether Perfusion Computed Tomography (P-CT) can qualitatively and quantitatively help detect gastric cancer neoangiogenesis in vivo as well as treatment response evaluation. We attempted to explore which P-CT parameters are best used in neoangiogenesis and neoadjuvant therapy for most effective evaluation. We also tried to recognize a positive prediction value of P-CT in early responders and non-responders patients identification. MATERIALS AND METHODS: Twenty-four patients with positive biopsy results and/or clinically proven gastric cancer were enrolled in the P-CT exam. Patients were qualified for systemic treatment (16 patients received chemotherapy and 8 patients received radiochemotherapy). The baseline Perfusion-CT exam and after neoadjuvant treatment Perfusion-CT exam were conducted using a 64-row GE tomograph based on a deconvolution model in first-pass protocol perfusion. The P CT examined the following parameters: Blood Flow (BF), Blood Volume (BV), Mean Transit Time (MTT) and Permeability Surface (PS). Positive clinical response to neoadjuvant treatment (CHT and RCT) was defined as tumor size reduction 25% or more. RESULTS: Tumor dimension reduction after neoadjuvant therapy was significantly correlated with the BF and the PS. Neoadjuvant therapy was more effective for patients with higher output BF and PS values. We did not register a significant relationship between BV and MTT parameters and tumor dimension reduction. Patients with a positive treatment response showed a decrease in BF, BV and PS perfusion parameters with an increase in MTT. CONCLUSIONS: P-CT examination allows a noninvasive neoangiogenesis assessment in vivo, leading to early identification of responding and non-responding patients. As a standard procedure, a full evaluation of treatment response should include a P-CT exam assessing neoangiogenesis. PMID- 28987698 TI - Diagnostic performance of MRI for prediction of muscle-invasiveness of bladder cancer: A systematic review and meta-analysis. AB - PURPOSE: To review the diagnostic performance of >=1.5-T MRI for local staging of bladder cancer. METHODS: MEDLINE and EMBASE were searched up to February 21, 2017. We included diagnostic accuracy studies published since 2000 that used >=1.5-T MRI for local staging (>=T2 [muscle-invasive]) in patients with bladder cancer, using pathology as the reference standard. The methodological quality was assessed using Quality Assessment of Diagnostic Accuracy Studies-2. Sensitivity and specificity were pooled and plotted in a hierarchical summary receiver operating characteristics plot. Sensitivity analyses using several clinically relevant covariates were performed. RESULTS: 24 studies (1774 patients) were included. Pooled sensitivity was 0.92 (95% CI 0.88-0.95) with specificity of 0.87 (95% CI 0.78-0.93). Sensitivity analyses showed that sensitivity estimates were comparable and consistently high across all subgroups, but specificity estimates were variable. Studies using 3-T scanners had higher specificity (0.93 [95% CI 0.86-0.98]) than those using 1.5-T scanners (0.83 [95% CI 0.74-0.98]). Studies using multiparametric MRI (conventional+>=2 functional sequences) showed the highest accuracy with sensitivity and specificity of 0.94 (95% CI 0.89-1.00) and 0.95 (95% CI 0.89-0.98), respectively. CONCLUSIONS: MRI shows good diagnostic performance for predicting muscle-invasiveness of bladder cancer. Multiparametric 3-T MRI seems to improve both sensitivity and specificity. PMID- 28987699 TI - Correlations between renal function and the total kidney volume measured on imaging for autosomal dominant polycystic kidney disease: A systematic review and meta-analysis. AB - PURPOSE: To provide a systematic summary of total kidney volume (TKV) as an imaging biomarker in clinical trials for autosomal dominant polycystic kidney disease (ADPKD), focusing on the correlation between TKV and renal function. METHODS: A computerized literature search was performed using MEDLINE and EMBASE databases for studies that evaluated the correlation between TKV and the glomerular filtration rate (GFR) and between the TKV growth rate and GFR decline rate. A meta-analysis was performed to generate the summary correlation coefficient (r). A qualitative review was performed to evaluate the characteristics of TKV as an imaging biomarker. RESULTS: Eighteen articles including a total sample size of 2835 patients were retrieved. Meta-analysis revealed substantial correlations between TKV and GFR [r, -0.520; 95% confidence interval (CI), -0.60 to -0.43] and between the TKV growth rate and GFR decline rate [r, -0.320; 95% CI, -0.54 to -0.10]. The quantitative review revealed that baseline TKV can affect the TKV growth rate and GFR decline rate, such that patients with a higher baseline TKV showed faster TKV growth and GFR decline. There was significant variability in image acquisition and analysis methods. CONCLUSION: There were significant negative correlations between TKV and GFR as well as between TKV growth and GFR decline rates, suggesting that TKV imaging is a useful biomarker in clinical trials. However, standardization-or at least trial specific standardization-of image acquisition and analysis techniques is required to use TKV as a reliable biomarker. PMID- 28987700 TI - Dual-modal computer-assisted evaluation of axillary lymph node metastasis in breast cancer patients on both real-time elastography and B-mode ultrasound. AB - PURPOSE: To propose a computer-assisted method for quantifying the hardness of an axillary lymph node on real-time elastography (RTE) and its morphology on B-mode ultrasound; and to combine the dual-modal features for differentiation of metastatic and benign axillary lymph nodes in breast cancer patients. MATERIALS AND METHODS: A total of 161 axillary lymph nodes (benign, n=69; metastatic, n=92) from 158 patients with breast cancer were examined with both B-mode ultrasound and RTE. With computer assistance, five morphological features describing the hilum, size, shape, and echogenic uniformity of a lymph node were extracted from B-mode, and three hardness features were extracted from RTE. Single-modal and dual-modal features were used to classify benign and metastatic nodes with two computerized classification approaches, i.e., a scoring approach and a support vector machine (SVM) approach. The computerized approaches were also compared with a visual evaluation approach. RESULTS: All features exhibited significant differences between benign and metastatic nodes (p<0.001), with the highest area under the receiver operating characteristic curve (AUC) of 0.803 and the highest accuracy (ACC) of 75.2% for a single feature. The SVM on dual-modal features achieved the largest AUC (0.895) and ACC (85.7%) among all methods, exceeding the scoring (AUC=0.881; ACC=83.6%) and the visual evaluation methods (AUC=0.830; ACC=84.5%). With the leave-one-out cross validation, the SVM on dual-modal features still obtained an ACC as high as 84.5%. CONCLUSION: Dual-modal features can be extracted from RTE and B-mode ultrasound with computer assistance, which are valuable for discrimination between benign and metastatic lymph nodes. The SVM on dual-modal features outperforms the scoring and visual evaluation methods, as well as all methods using single-modal features. The computer-assisted dual modal evaluation of lymph nodes could be potentially used in daily clinical practice for assessing axillary metastasis in breast cancer patients. PMID- 28987701 TI - Comparison of perioperative automated versus manual two-dimensional tumor analysis in glioblastoma patients. AB - OBJECTIVES: Current recommendations for the measurement of tumor size in glioblastoma continue to employ manually measured 2D product diameters of enhancing tumor. To overcome the rater dependent variability, this study aimed to evaluate the potential of automated 2D tumor analysis (ATA) compared to highly experienced rater teams in the workup of pre- and postoperative image interpretation in a routine clinical setting. MATERIALS AND METHODS: From 92 patients with newly diagnosed GB and performed surgery, manual rating of the sum product diameter (SPD) of enhancing tumor on magnetic resonance imaging (MRI) contrast enhanced T1w was compared to automated machine learning-based tumor analysis using FLAIR, T1w, T2w and contrast enhanced T1w. RESULTS: Preoperative correlation of SPD between two rater teams (1 and 2) was r=0.921 (p<0.0001). Difference among the rater teams and ATA (p=0.567) was not statistically significant. Correlation between team 1 vs. automated tumor analysis and team 2 vs. automated tumor analysis was r=0.922 and r=0.897, respectively (p<0.0001 for both). For postoperative evaluation interrater agreement between team 1 and 2 was moderate (Kappa 0.53). Manual consensus classified 46 patients as completely resected enhancing tumor. Automated tumor analysis agreed in 13/46 (28%) due to overestimation caused by hemorrhage and choroid plexus enhancement. CONCLUSIONS: Automated 2D measurements can be promisingly translated into clinical trials in the preoperative evaluation. Immediate postoperative SPD evaluation for extent of resection is mainly influenced by postoperative blood depositions and poses challenges for human raters and ATA alike. PMID- 28987702 TI - The diagnostic accuracy of neck ultrasound, 4D-Computed tomographyand sestamibi imaging in parathyroid carcinoma. AB - INTRODUCTION: Our aim was to investigate the accuracy of available imaging modalities for parathyroid carcinoma (PC) in our institution and to identify which imaging modality, or combination thereof, is optimal in preoperative determination of precise tumor location. METHODS: All operated PC patients in our institution between 2000 and 2015 that had at least one of the following in-house preoperative scans: neck ultrasonography (US), neck 4D-Computed Tomography (4DCT) and 99mTc Sestamibi SPECT/CT (MIBI). Sensitivity, specificity and accuracy of PC tumor localization were assessed individually and in combination. RESULTS: 20 patients fulfilled the inclusion criteria and were analysed. There were 18 US, 18 CT and 9 MIBI scans. The sensitivity and accuracy for tumor localisation of US was 80% (CI 56-94%) and 73% respectively, of 4DCT was 79% (CI 58-93%) and 82%, and of MIBI was 81% (CI 54-96%) and 78%. The sensitivity and accuracy of the combination of CT and MIBI was 94% (CI 73-100%) and 95% and for the combination of US, CT and MIBI was 100% (CI 72-100%) and 100% respectively. The wash-out of the PC lesions, expressed as a percentage change in Hounsfield Units from the arterial phase to early delayed phase was -9.29% and to the late delayed phase was -16.88% (n=11). CONCLUSIONS: The sensitivity of solitary preoperative imaging of PC patients, whether by US, CT or MIBI, is approximately 80%. Combinations of CT with MIBI and US increase the sensitivity to 95% or better. Combined preoperative imaging of patients with clinical possibility of PC is therefore recommended. PMID- 28987704 TI - The role of colour doppler ultrasonography of facial and occipital arteries in patients with giant cell arteritis: A prospective study. AB - OBJECTIVE: Colour Doppler Sonography (CDS) in giant cell arteritis (GCA) allows the study of involvement of cranial arteries other than the temporal arteries, which are inconvenient to biopsy, such as the facial (FaA), and occipital (OcA) arteries. We aimed to estimate the frequency of the FaA, and OcA involvement in GCA; and to explore the clinical characteristics of these subgroups of patients. METHODS: From 1 January 2014 to 31 December 2016 we prospectively performed a CDS of the FaA, and OcA in addition to the temporal (TA), and the extracranial supra aortic arteries in all newly diagnosed patients suspected of having GCA. All the arteries were evaluated in two planes for the highly specific halo sign. RESULTS: During the 36-month observation period we performed a CDS of the cranial and extra-cranial arteries in 93 GCA patients. We observed the halo sign on the FaA, and OcA in 38 (40.9%), and 29 (31.2%) cases, respectively. The FaA, or OcA were affected in 4/22 (18.2%) patients with a negative TA CDS. FaA involvement significantly correlated with jaw claudication and with severe visual manifestations, including permanent visual loss. CONCLUSIONS: A fifth of patients with a negative CDS of the TAs had signs of vasculitis on the CDS of the FaA, or OcA. The addition of FaA and OcA CDS to the routine CDS of the TAs could identify 4.3% more patients and thus further improve the sensitivity of the CDS in the suspected GCA. PMID- 28987703 TI - Early myocardial gadolinium enhancement in patients with myocarditis: Validation of "Lake Louise consensus" criteria using a single bolus of 0.1mmol/Kg of a high relaxivity gadolinium-based contrast agent. AB - OBJECTIVES: Global early gadolinium enhancement (EGE) is an accepted cardiac magnetic resonance (CMR) criterion for diagnosis of myocarditis. However, recommended enhancement thresholds are based specifically on standard-relaxivity Gd-chelates. We evaluated the performance of a high relaxivity MR contrast agent for detection of myocardial hyperemia in patients referred for endomyocardial biopsy (EMB). METHODS: We retrospectively enrolled 54 patients (mean age: 44.1 years [range=18-77years]; 72% men) with suspected myocarditis who underwent CMR and EMB within four weeks of clinical onset. CMR imaging protocol included T2 weighted short tau inversion-recovery sequence, EGE and late gadolinium enhanced (LGE) imaging. For EGE imaging, free-breathing ECG-gated turbo spin echo T1 weighted (TSE T1w) sequences were acquired before and within the first three minutes after gadobenate dimeglumine (0.1mmol/Kg) administration. The ratio (EGEr) between myocardial and musculoskeletal early enhancement was calculated. Myocardial edema, EGE and late gadolinium enhancement (LGE) were correlated with EMB results. Receiver operating characteristic (ROC) curve analysis of EGE values was applied on the overall population. RESULTS: EMB revealed myocarditis in 34/54 patients. Sensitivity, specificity and accuracy values of 0.61, 0.85 and 0.70, respectively, were obtained for a standard EGE threshold (EGEr>4.0). ROC analysis revealed an area under the curve of 0.701 for EGEr (IC95%:0.556-0.846, p=0.014) and 0.706 for absolute enhancement (IC95%:0.563-0.849, p=0.012). Sensitivity, specificity and accuracy values were 0.67, 0.80 and 0.72, respectively, for myocardial edema and 0.76, 0.75 and 0.76, respectively, for LGE. CONCLUSIONS: High relaxivity contrast agents provide comparable results to standard-relaxivity chelates for EGE assessment in diagnosing myocarditis. PMID- 28987705 TI - Evaluation of inter-observer variability according to RECIST 1.1 and its influence on response classification in CT measurement of liver metastases. AB - OBJECTIVE: The aim of this study is the evaluation of inter-observer variability in the measurement of liver metastases according to RECIST and its influence on response classification. PATIENTS AND METHODS: A total of 100 radiologists measured liver target lesions, on pre- and post-chemotherapy CT scans of three patients. Each observer filled out a questionnaire about his personal and work features. The evaluations of a well experienced radiologist, considered as "the gold standard", were compared to those taken by the observers. The percentage of the observers in agreement with the reviewer, in terms of the response category and in terms of inter-observer variability, was calculated for each patient. RESULTS: The percentage of the inter-observer agreement was elevated. Most of the observers in agreement with the reviewer were senior radiologists, while those who disagreed were junior radiologist, but this result did not reach a statistical significance. More than 30% of observers disagreed with the reviewer at least in one of the three cases. CONCLUSIONS: RECIST measurements are reproducible on a large and heterogeneous population of radiologists. Age and expertise of the radiologist remain the most critical factors: this suggests a revision by well-experienced radiologists in clinical trials. PMID- 28987707 TI - Epilepsy, language, and social skills. AB - Language and social skills are essential for intrapersonal and interpersonal functioning and quality of life. Since epilepsy impacts these important domains of individuals' functioning, understanding the psychosocial and biological factors involved in the relationship among epilepsy, language, and social skills has important theoretical and clinical implications. This review first describes the psychosocial and biological factors involved in the association between language and social behavior in children and in adults and their relevance for epilepsy. It reviews the findings of studies of social skills and the few studies conducted on the inter-relationship of language and social skills in pediatric and adult epilepsy. The paper concludes with suggested future research and clinical directions that will enhance early identification and treatment of epilepsy patients at risk for impaired language and social skills. PMID- 28987708 TI - Von Willebrand disease mutation spectrum and associated mutation mechanisms. AB - Von Willebrand disease (VWD) is a bleeding disorder that is mainly caused by mutations in the multimeric protein von Willebrand factor (VWF). These mutations may lead to deficiencies in plasma VWF or dysfunctional VWF. VWF is a heterogeneous protein and over the past three decades, hundreds of VWF mutations have been identified. In this review we have organized all reported mutations, spanning a timeline from the late eighties until early 2017. This resulted in an overview of 750 unique mutations that are divided over the VWD types 1, 2A, 2B, 2M, 2N and 3. For many of these mutations the disease-causing effects have been characterized in vitro through expression studies, ex vivo by analysis of patient derived endothelial cells, as well as in animal or (bio)physical models. Here we describe the mechanisms associated with the VWF mutations per VWD type. PMID- 28987709 TI - Impact of levosimendan on platelet function. AB - Levosimendan has been developed for treatment of severe heart failure. The favorable hemodynamic effect of levosimendan is related to its unique dual mechanism of action - increase of the contractile force of the myocardium caused by enhanced sensitivity of myofilaments to calcium combined with vasodilatation caused by the opening of adenosine triphosphate - dependent potassium channels. Due to the structural similarities to phosphodiesterase inhibitors it may partly exert its action via inhibition of phosphodiesterase inhibitors III. Inhibition of the phosphodiesterase inhibitors III leads to an increase of intracellular concentration of cyclic adenosine monophosphate causing an anti-aggregatory effect. There are some contradictory or indirect and inconclusive reports related to the impact of levosimendan on platelet function. The aim of this systematic review was to critically discuss the impact of levosimendan on platelet function according to currently available knowledge based on the findings of experimental as well as observational and randomized clinical studies. PMID- 28987706 TI - Combined effects of prenatal exposure to polycyclic aromatic hydrocarbons and material hardship on child ADHD behavior problems. AB - IMPORTANCE: Polycyclic aromatic hydrocarbons (PAH) are carcinogenic and neurotoxic combustion by-products commonly found in urban air. Exposure to PAH is disproportionately high in low income communities of color who also experience chronic economic stress. OBJECTIVE: In a prospective cohort study in New York City (NYC) we previously found a significant association between prenatal PAH exposure and Attention Deficit Hyperactivity Disorder (ADHD) behavior problems at age 9. Here, we have evaluated the joint effects of prenatal exposure to PAH and prenatal/childhood material hardship on ADHD behavior problems. MATERIALS AND METHODS: We enrolled nonsmoking African-American and Dominican pregnant women in New York City between 1998 and 2006 and followed their children through 9 years of age. As a biomarker of prenatal PAH exposure, PAH-DNA adducts were measured in maternal blood at delivery and were dichotomized at the limit of detection (to indicate high vs. low exposure). Maternal material hardship (lack of adequate food, housing, utilities, and clothing) was self-reported prenatally and at multiple time points through child age 9. Latent variable analysis identified four distinct patterns of hardship. ADHD behavior problems were assessed using the Conners Parent Rating Scale- Revised. Analyses adjusted for relevant covariates. RESULTS: Among 351 children in our sample, across all hardship groups, children with high prenatal PAH exposure (high adducts) generally had more symptoms of ADHD (higher scores) compared to those with low PAH exposure. The greatest difference was seen among the children with hardship persisting from pregnancy through childhood. Although the interactions between high PAH exposure and hardship experienced at either period ("persistent" hardship or "any" hardship) were not significant, we observed significant differences in the number of ADHD symptoms between children with high prenatal PAH exposure and either persistent hardship or any hardship compared to the others. These differences were most significant for combined high PAH and persistent hardship: ADHD Index (p < 0.008), DSM-IV Inattentive (p = 0.006), DSM-IV Hyperactive Impulsive problems (p = 0.033), and DSM-IV Index Total (p = 0.009). CONCLUSION: The present findings add to existing evidence that co-exposure to socioeconomic disadvantage and air pollution in early life significantly increases the risk of adverse neurodevelopmental outcomes. They suggest the need for multifaceted interventions to protect pregnant mothers and their children. PMID- 28987710 TI - Special health care needs explains the effect of extremely low birth weight on math but not language achievement. AB - OBJECTIVES: Extremely low birth weight (ELBW; <1kg) adolescents are at risk for special health care needs (SHCN) and poor math achievement compared to normal birth weight (NBW) peers. SHCN are associated with poor academic achievement among NBW children. We hypothesize that SHCN explain the effect of ELBW on math achievement. METHODS: We compared age 14 Woodcock-Johnson Calculation standard scores between 181 ELBW infants and 115 NBW controls. Persistent SHCN included: 1) prescription medication or equipment use, 2) subspecialty or therapeutic service use, or 3) hospitalization. We used nonlinear marginal effects models to decompose the total effect of ELBW on math into the following 4 components: the effect of ELBW controlling for SHCN, the effect of SHCN controlling for ELBW, effect modification by SHCN, and mediated interaction where SHCN is both causal mediator and effect modifier. Models were adjusted for sociodemographic factors. RESULTS: ELBW adolescents had lower mean math scores than NBW peers (81.3 vs. 96.4). SHCN were more common among ELBW adolescents (54.1% vs. 27%). The total effect of ELBW on math scores was -15.7 points (95% CI -21.0, -10.5). The effect of birth weight alone was -7.6 points (95% CI -13.7, -1.4); the effect of SHCN alone was negligible. SHCN interaction and mediated interaction effects each accounted for 25% of the total effect. CONCLUSIONS: Birth weight alone explains only half of the effect of ELBW on math achievement. We found evidence of effect modification and mediation by SHCN. Understanding these explanatory pathways may lead to targeted interventions for improved outcomes. PMID- 28987711 TI - Optimization of digital image processing to determine quantum dots' height and density from atomic force microscopy. AB - An optimized method of digital image processing to interpret quantum dots' height measurements obtained by atomic force microscopy is presented. The method was developed by combining well-known digital image processing techniques and particle recognition algorithms. The properties of quantum dot structures strongly depend on dots' height, among other features. Determination of their height is sensitive to small variations in their digital image processing parameters, which can generate misleading results. Comparing the results obtained with two image processing techniques - a conventional method and the new method proposed herein - with the data obtained by determining the height of quantum dots one by one within a fixed area, showed that the optimized method leads to more accurate results. Moreover, the log-normal distribution, which is often used to represent natural processes, shows a better fit to the quantum dots' height histogram obtained with the proposed method. Finally, the quantum dots' height obtained were used to calculate the predicted photoluminescence peak energies which were compared with the experimental data. Again, a better match was observed when using the proposed method to evaluate the quantum dots' height. PMID- 28987712 TI - Heritability of Schizophrenia and Schizophrenia Spectrum Based on the Nationwide Danish Twin Register. AB - BACKGROUND: Twin studies have provided evidence that both genetic and environmental factors contribute to schizophrenia (SZ) risk. Heritability estimates of SZ in twin samples have varied methodologically. This study provides updated heritability estimates based on nationwide twin data and an improved statistical methodology. METHODS: Combining two nationwide registers, the Danish Twin Register and the Danish Psychiatric Research Register, we identified a sample of twins born between 1951 and 2000 (N = 31,524 twin pairs). Twins were followed until June 1, 2011. Liability threshold models adjusting for censoring with inverse probability weighting were used to estimate probandwise concordance rates and heritability of the diagnoses of SZ and SZ spectrum disorders. RESULTS: The probandwise concordance rate of SZ is 33% in monozygotic twins and 7% in dizygotic twins. We estimated the heritability of SZ to be 79%. When expanding illness outcome to include SZ spectrum disorders, the heritability estimate was almost similar (73%). CONCLUSIONS: The key strength of this study is the application of a novel statistical method accounting for censoring in the follow up period to a nationwide twin sample. The estimated 79% heritability of SZ is congruent with previous reports and indicates a substantial genetic risk. The high genetic risk also applies to a broader phenotype of SZ spectrum disorders. The low concordance rate of 33% in monozygotic twins demonstrates that illness vulnerability is not solely indicated by genetic factors. PMID- 28987714 TI - Diagnosis and management of pyriform sinus cyst in neonates: 16-year experience at a single center. AB - BACKGROUND/PURPOSE: The purpose of this study was to review our experience in diagnosing and managing neonatal pyriform sinus cyst (PSC) and to assess its outcomes. METHODS: We retrospectively reviewed 38 cases of neonatal PSC from 2001 to 2016. Clinical features, PSC diagnosis, treatment, and outcomes were analyzed. RESULTS: Cervical masses were detected prenatally in 8 patients (21.1%). Neck cyst and respiratory distress were frequent symptoms among these patients. Preoperative PSC diagnosis was made in 15 cases (39.5%) by esophagography. CT or MRI images showed an air-filled cyst in 22 patients (57.9%). Cyst drainage was performed in 8 infected cases (21.1%). Cyst and fistula excision was performed in 30 cases (78.9%). Fistula excision assisted by endoscopy was required in 13 PSC patients (34.2%). Fistula detection failed in 4 cases (10.5%). Patients aged between 0 to 7days presented with low infection and high cyst removal rate. No fistula recurrence occurred in cases with cyst resection. CONCLUSIONS: CT or MRI images with an air-filled cyst are significant indications in diagnosing PSC. Surgical options for PSC depend on levels of cervical infection. The optimal timing for surgical intervention is between 0 to 7days after birth. Our surgical approaches were effective in treating neonatal PSC. LEVELS OF EVIDENCE: Treatment study, level IV (retrospective study). PMID- 28987713 TI - Radiographic measurement of intestinal length among children with short bowel syndrome: Retrospective determination remains problematic. AB - PURPOSE: Small bowel length is the most reliable predictor of enteral independence in pediatric short bowel syndrome. Retrospectively measured bowel lengths on upper GI with small bowel follow-through (UGI/SBFT) were compared to operative measurements. METHODS: A pediatric radiologist and surgical trainees blinded to operative measurements retrospectively analyzed UGI/SBFT studies using the digital radiography curved measurement tool. Children with SBS and severe intestinal failure (parenteral nutrition >90days) at a multidisciplinary intestinal failure program 2002-2015 were included. Data were expressed as median (Q1, Q3). RESULTS: Thirty-six children aged 0.8 (0.4, 3.7) years were analyzed. Fifty-six percent had intestinal malrotation, and 58% had prior serial transverse enteroplasty. Studies were conducted within 10 (7, 20) days of surgery. Intraoperative bowel length was 90cm (45, 142), while UGI/SBFT measurement by radiologist was 45cm (28, 63), with a mean difference of 47cm (SD 58cm, p<0.001) and a mean percent error of 50%. Radiographic assessment underestimated intestinal length in 83% of patients. CONCLUSION: Bowel length measured retrospectively from upper GI with small bowel follow-through studies usually underestimated intraoperative bowel length. The limits of agreement were too wide for this technique to be clinically useful. Operative measurement remains necessary to assess intestinal length and rehabilitation potential. TYPE OF STUDY: Study of Diagnostic Test. LEVEL OF EVIDENCE: Level III. PMID- 28987715 TI - Mitigating fall risk: A community fall reduction program. AB - One fourth of all American's over 65 years of age fall each year. Falls are a common and often devastating event that can pose a serious health risk for older adults. Healthcare providers are often unable to spend the time required to assist older adults with fall risk issues. Without a team approach to fall prevention the system remains focused on fragmented levels of health promotion and risk prevention. The specific aim of this project was to engage older adults from the community in a fall risk assessment program, using the Stopping Elderly Accidents, Deaths & Injuries (STEADI) program, and provide feedback on individual participants' risks that participants could share with their primary care physician. Older adults who attended the risk screening were taking medications that are known to increase falls. They mentioned that their health care providers do not screen for falls and appreciated a community based screening. PMID- 28987716 TI - A validated method for analyzing polyunsaturated free fatty acids from dried blood spots using LC-MS/MS. AB - Omega-3 and omega-6 polyunsaturated free fatty acids (PUFA-FFA) are precursors to potent downstream lipid mediators that are regulators of inflammation. We describe the development and validation of a novel and sensitive method for quantification of individual PUFA-FFA in a dried blood spot using liquid chromatography tandem mass spectrometry (LC-MS/MS). Lipids were extracted from dried blood spot and six individual PUFA-FFA were quantified by LC-MS/MS using stable isotope dilution analysis with deuterated internal standards. PUFA-FFA concentrations in blood samples from 30 subjects were measured using the new method and compared to the traditional approach of thin layer chromatography followed by gas chromatography with flame ionization detection (TLC-GC). Responses for each PUFA-FFA were linear throughout a range of concentrations expected in clinical samples. Intra-day and inter-day variations for all PUFA-FFA were <= 16%. The concentrations of all PUFA-FFA measured by LC-MS/MS were positively correlated with measures of the same PUFA-FFA obtained by a traditional TLC-GC method. This novel method for the quantification of PUFA-FFA extracted from dried blood is sensitive and precise, and accurately measures levels of biologically important PUFA-FFA in blood. PMID- 28987717 TI - Protective effect of Rumenic acid rich cow's milk against colitis is associated with the activation of Nrf2 pathway in a murine model. AB - Dietary supplementation with pure cis9, trans11 isomer of Conjugated Linoleic Acid -known as Rumenic Acid (RA)- improves cytoprotective defenses downstream through the activation of nuclear factor-E2-related factor-2(Nrf2). This capability, when Rumenic Acid is consumed in the form of foods, is still unknown. The ability of standard (St) or cow milk naturally-enriched in RA (En) to activate Nrf2 pathway and its impact on dextran sodium sulfate (DSS)-induced colitis was comparatively evaluated. Activity of Nrf2 pathway was investigated in colonic tissue of BALB/c mice, receiving 4-week supplement with skimmed milk (SK), St or St reinforced with pure RA (RSt) providing increasing RA dose (0, 124 or 404mg RA/kg-1 b.w, respectively). Next, the anti-oxidant/ anti-inflammatory effect produced by St or En treatment (383mg RA/kg-1 b.w.) was explored. Finally, macroscopic and histomorphologic features of colitis were evaluated in animals challenged with 5% (w/v) DSS, at the end of St or En treatment. Significant activation of Nrf2 pathway is associated with RSt and En intake (P<0.05), but not with SK or En treatment. En pre-treatment offers better protection, in comparison with St, against pro-oxidant, pro-inflammatory signs (P<0.01) and macroscopic signs triggered by DSS. It can be concluded that Nrf2 activation by higher RA amount contained in En is, at least in part, responsible for the improved protection associated with En intake against DSS-induced colitis. PMID- 28987718 TI - Fatty acid profile of maternal and fetal erythrocytes and placental expression of fatty acid transport proteins in normal and intrauterine growth restriction pregnancies. AB - Long-chain polyunsaturated fatty acids (LC-PUFA), mainly docosahexaenoic (DHA) and arachidonic acids (AA), are critical for adequate fetal growth and development. We investigated mRNA expression of proteins involved in hydrolysis, uptake and/or transport of fatty acids in placenta of fifteen full term normal pregnancies and eleven pregnancies complicated by intrauterine growth restriction (IUGR) with normal umbilical blood flows. The mRNA expression of LPL, FATPs (-1, 2 and -4) and FABPs (-1 and -3) was increased in IUGR placentas, however, tissue profile of LC-PUFA was not different between groups. Erythrocytes from both mothers and fetuses of the IUGR group showed lower concentrations of AA and DHA and inferior DHA/ALA ratio compared to normal pregnancies (P < 0.05). We hypothesize that reduced circulating levels of AA and DHA could up-regulate mRNA expression of placental fatty acids transporters, as a compensatory mechanism, however this failed to sustain normal LC-PUFA supply to the fetus in IUGR. PMID- 28987719 TI - Supplementation of docosahexaenoic acid (DHA) / Eicosapentaenoic acid (EPA) in a ratio of 1/1.3 during the last trimester of pregnancy results in EPA accumulation in cord blood. AB - Omega-3 fatty acids (n-3 FA), specifically DHA, are associated with fetal growth and development. We aimed to determine the levels of DHA and EPA in cord serum after n-3 FA supplementation during the last trimester of pregnancy. Among 55 women, 23 were administered daily one capsule of n-3 FA supplement, involving DHA/EPA in a ratio of 1/1.3. Twenty nine women were enrolled as control group. Blood samples were collected at 22-24 weeks of gestation and at delivery. Fatty acids were analyzed with the method of GC-MS. Cord DHA level increased and EPA level decreased in both groups between the days of 22-24 and delivery. However, decrease in cord EPA level was significant in control group (p < 0.001) but not in supplement group (p > 0.05). Supplementation of DHA/EPA in a ratio of 1/1.3 during the last trimester of pregnancy caused higher cord EPA level compared to control group indicating an accumulation in umbilical cord. PMID- 28987720 TI - Long chain n-3 polyunsaturated fatty acids are not associated with circulating T helper type 1 cells: Results from the Multi-Ethnic Study of Atherosclerosis (MESA). AB - T-helper type 1 (Th1) cells are pro-inflammatory and provide signals to immune cells. Animal models and in vitro human cell culture experiments have indicated that long chain n-3 polyunsaturated fatty acids (LCn3PUFAs) reduce Th1 cell levels; however, the association is unknown in healthy humans. We hypothesized that circulating levels and dietary intake of LCn3PUFAs have an inverse association with circulating levels of Th1 cells and studied 895 participants in the Multi-Ethnic Study of Atherosclerosis (age 61 +/- 10 years at exam 1, 52% women, 44% white, 21% African-American, 24% Hispanic-American, 11% Chinese American). Phospholipid LCn3PUFAs (% of total fatty acids), measured by gas chromatography, and intake of LCn3PUFAs, evaluated by food frequency questionnaire, were evaluated at exam 1 (2000-02) and defined as the sum of eicosapentaenoic and docosahexaenoic acids. Th1 cells were measured by flow cytometry at exam 4 (2005-07), expressed as a percentage of CD4+ lymphocytes that were interferon-gamma+ (%Th1: CD4+IFN-gamma+). Median (interquartile range) plasma LCn3PUFA, dietary LCn3PUFA, and %Th1 levels were 4.31% (3.40-5.82%), 0.09 (0.05-0.16) g/day, and 14.4% (9.8-20.0%), respectively. When the association of LCn3PUFA-quartiles with %Th1 was analyzed using general linear models, neither plasma nor dietary LCn3PUFAs were significantly associated with %Th1 (P-trend = 0.58 and 0.80, respectively), which remained even after adjusting for demographics, lifestyle factors, lipids, season, and cytomegalovirus titers. In this multi-ethnic U.S. population, circulating levels and dietary intake of LCn3PUFAs were not significantly associated with Th1 cell levels. Further research is needed to assess potential benefits of supplementation and much higher dietary consumption of LCn3PUFAs on Th1 cells. PMID- 28987722 TI - The effects of omega-6 and omega-3 fatty-acids on early stages of mice DMBA submandibular glands tumorigenesis. AB - The aim of this work was: to assess the impact of diets enriched in polyunsaturated fatty acids omega-3 and omega-6 families on the lipid profile of cell membrane and their effect on cycle regulation and apoptosis, evaluated by TP53 and Ki-67 expression in 9,10-dimethyl-1,2-benzanthracene (DMBA) induced tumor development in submandibular glands (SMG) in murine models. To generate tumorigenic changes, SMG mice in the experimental group were injected with 50MUl of 0.5% of DMBA. Both control (no DMBA) and experimental groups of BALB/c mice were fed with: chia oil (ChO), rich in omega-3 fatty acid; corn oil (CO), rich in omega-6/omega-3 fatty acid; and safflower (SO) oil, rich in omega-6fatty acid. Results demonstrate novel differential effects of omega-3 and omega-6 PUFAs on the regulation of early tumorigenesis events in murine SMG injected with DMBA. This knowledge may help to develop chemoprotective treatments, therapeutic agents and health promotion and prevention activities in humans. PMID- 28987721 TI - Circulating inflammation-resolving lipid mediators RvD1 and DHA are decreased in patients with acutely symptomatic carotid disease. AB - BACKGROUND: Efficient biomarkers for early prediction and diagnosis of an acutely symptomatic carotid plaque rupture event are currently lacking, impairing the ability to diagnose and treat patients with an acute plaque rupture events in a timely fashion. Resolvins are endogenous inflammation-resolving lipid mediators that are induced by inflammatory insults. We hypothesized that resolvin and other lipid profiles in sera likely mark the process towards plaque rupture. METHODS: Circulating lipids associated with plaque rupture events were quantitatively profiled via targeted mediator-lipidomics using ultraperformance liquid chromatography tandem mass spectrometry in patients with acutely symptomatic and asymptomatic carotid disease. RESULTS: Resolvin D1 (RvD1, 82 +/- 11pM vs. 152 +/- 17pM, p = 0.001) and docosahexaenoic acid (DHA) (0.052 +/- 0.007uM versus 0.076 +/- 0.008uM, p = 0.025) levels are decreased in the sera of patients presenting with an acutely symptomatic carotid plaque rupture event (n = 21) compared to patients with asymptomatic (n = 24) high-grade carotid stenosis. Circulating arachidonic acid (AA) levels, however, were higher (0.429 +/- 0.046uM versus 0.257 +/- 0.035uM, p < 0.01) in acutely symptomatic compared to asymptomatic carotid patients. ROC curve analysis demonstrates that the serum ratio AA:RvD1 (AUC 0.84, sensitivity 0.71, specificity 0.92) and AA:DHA (AUC 0.86, sensitivity 0.90, specificity 0.71) are biomarkers for the risk of atherosclerotic plaque rupture. CONCLUSIONS: A circulating pro-inflammatory lipid profile, characterized by high AA:RvD1 and AA:DHA, is associated with acutely symptomatic carotid disease and stroke. PMID- 28987723 TI - Low dose aspirin increases 15-epi-lipoxin A4 levels in diabetic chronic kidney disease patients. AB - BACKGROUND: Resolution of inflammation is regulated by endogenous lipid mediators, such as lipoxins and their epimers, including 15-epi-lipoxin A4 (15 epi-LXA4). However, there is no information on 15-epi-LXA4 and its in vivo regulation in chronic kidney disease (CKD) patients. STUDY DESIGN: Open label randomized clinical trial. SETTING AND PARTICIPANTS: 50 participants with chronic kidney disease (CKD) stage 3 and 4 without prior cardiovascular disease (25 in the aspirin group and 25 in the standard group) followed for 46 months. INTERVENTION: Aspirin (100mg/day) or standard treatment. AIM: To analyze the effect of aspirin on plasma 15-epi-LXA4 levels and inflammatory markers in CKD patients. RESULTS: Baseline plasma15-epi-LXA4 levels were lower in diabetic (1.22 +/- 0.99ng/ml) than in non-diabetic CKD patients (2.05 +/- 1.06ng/ml, p < 0.001) and inversely correlated with glycosylated hemoglobin levels (r = -0.303, p = 0.006). In multivariate analysis, diabetes was associated with lower 15-epi-LXA4 levels, adjusted for age, inflammatory markers and renal function (p = 0.005). In the whole study population, 15-epi-LXA4 levels tended to increase, but not significantly (p = 0.45), after twelve months on aspirin (from mean +/- SD 1.84 +/- 1.06 to 2.04 +/- 0.75ng/ml) and decreased in the standard care group (1.60 +/ 1.15 to 1.52 +/- 0.68ng/ml, p = 0.04). The aspirin effect on 15-epi-LXA4 levels was more striking in diabetic patients, increasing from 0.94 +/- 0.70 to 1.93 +/- 0.74ng/ml, p = 0.017. CONCLUSIONS: Diabetic patients with CKD have lower circulating 15-epi-LXA4 levels than non-diabetic CKD patients. Low dose aspirin for 12 months increased 15-epi-LXA4 levels in diabetic patients. Given its anti inflammatory properties, this increase in 15-epi-LXA4 levels may contribute to the beneficial effects of low dose aspirin. PMID- 28987724 TI - Effect of Proanthocyanidin-enriched extracts on the inhibition of wear and degradation of dentin demineralized organic matrix. AB - OBJECTIVES: The aim of this study was to evaluate the effect of Cranberry and Grape seed-enriched extract gels in inhibiting wear and degradation of demineralized organic matrix (DOM). DESIGN: 225 dentin specimens obtained from bovine incisors were randomly allocated into 5 groups (n=45): 10% Grape seed extract gel (GSE), 10% Cranberry extract gel (CE), 0.012% Chlorhexidine gel (CX), 1.23% NaF gel (F), and no active compound gel (P, placebo). Before the treatments, samples were demineralized by immersion in 0.87M citric acid, pH 2.3 (36h). Then, the studied gels were applied once over dentin for 1min. Next, the samples were immersed in artificial saliva containing collagenase obtained from Clostridium histolyticum for 5days. The response variable for dentin wear was depth of dentin loss measured by profilometry and for collagen degradation was hydroxyproline determination. Data were analyzed by ANOVA followed by Tukey's test and Pearson Correlation Test (p<0.05). RESULTS: Grape seed extract significantly reduced dentin wear compared to the other groups (p<0.05). Cranberry extract and Chlorhexidine did not differ statistically and were able to reduce wear when compared to NaF and placebo treatments. The hydroxyproline analysis showed that there was no significant difference among groups for all treatments (p<0.05). Correlation analysis showed a significant correlation between the amount of degraded DOM evaluated by profilometry and the determination of hydroxyproline. CONCLUSION: Cranberry extract was able to reduce the dentin wear and collagen degradation, likely due to the proanthocyanidin content and its action. Therefore, Cranberry could be suggested as an interesting natural-based agent to prevent dentin erosion. PMID- 28987725 TI - Mechanical and hypoxia stress can cause chondrocytes apoptosis through over activation of endoplasmic reticulum stress. AB - OBJECTIVE: To examine the role of mechanical force and hypoxia on chondrocytes apoptosis and osteoarthritis (OA)-liked pathological change on mandibular cartilage through over-activation of endoplasmic reticulum stress (ERS). METHODS: We used two in vitro models to examine the effect of mechanical force and hypoxia on chondrocytes apoptosis separately. The mandibular condylar chondrocytes were obtained from three-week-old male Sprague-Dawley rats. Flexcell 5000T apparatus was used to produce mechanical forces (12%, 0.5Hz, 24h vs 20%, 0.5Hz, 24h) on chondrocytes. For hypoxia experiment, the concentration of O2 was down regulated to 5% or 1%. Cell apoptosis rates were quantified by annexin V and propidium iodide (PI) double staining and FACS analysis. Quantitative real-time PCR and western blot were performed to evaluate the activation of ERS and cellular hypoxia. Then we used a mechanical stress loading rat model to verify the involvement of ERS in OA-liked mandibular cartilage pathological change. Histological changes in mandibular condylar cartilage were assessed via hematoxylin & eosin (HE) staining. Immunohistochemistry of GRP78, GRP94, HIF 1alpha, and HIF-2alpha were performed to evaluate activation of the ERS and existence of hypoxia. Apoptotic cells were detected by the TUNEL method. RESULTS: Tunicamycin, 20% mechanical forces and hypoxia (1% O2) all significantly increased chondrocytes apoptosis rates and expression of ERS markers (GRP78, GRP94 and Caspase 12). However, 12% mechanical forces can only increase the apoptotic sensitivity of chondrocytes. Mechanical stress resulted in OA-liked pathological change on rat mandibular condylar cartilage which included thinning cartilage and bone erosion. The number of apoptotic cells increased. ERS and hypoxia markers expressions were also enhanced. Salubrinal, an ERS inhibitor, can reverse these effects in vitro and in vivo through the down-regulation of ERS markers and hypoxia markers. CONCLUSION: We confirmed that mechanical stress and local hypoxia both contributed to the chondrocytes apoptosis. Mechanical stress can cause OA-like pathological change in rat mandibular condylar cartilage via ERS activation and hypoxia existed in the meantime. Both mechanical forces and hypoxia can induce ERS and cause chondrocytes apoptosis only if the stimulate was in higher level. Salubrinal can protect chondrocytes from apoptosis, and relieve OA-liked pathological change on mandibular condylar cartilage under mechanical stress stimulation. PMID- 28987726 TI - Inhibition of malodorous gas formation by oral bacteria with cetylpyridinium and zinc chloride. AB - OBJECTIVE: The antimicrobial efficacy of zinc- (ZnCl2) and cetylpyridinium chloride (CPC) and their inhibition capacity on volatile sulfur compound (VSC) production by oral bacterial strains were investigated. DESIGN: Minimum inhibitory concentrations (MIC) and growth curves were determined for ZnCl2, CPC, and CPC with ZnCl2 solutions against eight oral microorganisms (Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella intermedia, Treponema denticola, Tannerella forsythia, Staphylococcus aureus and Streptococcus mutans) known to be involved in the pathophysiology of both halitosis and periodontal disease. Gas chromatography was applied to measure VSCs (H2S, CH3SH, (CH3)2S) production levels of each strains following exposure to the solutions. RESULTS: ZnCl2 and CPC effectively inhibited growth of all eight strains. ZnCl2 was generally more effective than CPC in suppressing bacterial growth excluding A. actinomycetemcomitans, P. intermedia, and T. forsythia. Synergism between CPC and ZnCl2 was shown in A. actinomycetemcomitans. The MIC for CPC was significantly lower than ZnCl2. VSC production was detected in five bacterial strains (A. actinomycetemcomitans, F. nucleatum, P. gingivalis, T. denticola, and T. forsythia). Each bacterial strain showed unique VSCs production profiles. H2S was produced by F. nucleatum, P. gingivalis, and T. denticola, CH3SH by all five strains and (CH3)2S by A. actinomycetemcomitans, F. nucleatum, P. gingivalis, and T. denticola. Production of CH3SH, the most malodorous component among the three major VSCs from mouth air was evident in F. nucleatum and T. forsythia. CONCLUSION: Both ZnCl2 and CPC effectively inhibit bacterial growth causative of halitosis and periodontal disease, resulting in a direct decrease of bacterial VSCs production. PMID- 28987727 TI - Assessment and uncertainty analysis of groundwater risk. AB - Groundwater with relatively stable quantity and quality is commonly used by human being. However, as the over-mining of groundwater, problems such as groundwater funnel, land subsidence and salt water intrusion have emerged. In order to avoid further deterioration of hydrogeological problems in over-mining regions, it is necessary to conduct the assessment of groundwater risk. In this paper, risks of shallow and deep groundwater in the water intake area of the South-to-North Water Transfer Project in Tianjin, China, were evaluated. Firstly, two sets of four level evaluation index system were constructed based on the different characteristics of shallow and deep groundwater. Secondly, based on the normalized factor values and the synthetic weights, the risk values of shallow and deep groundwater were calculated. Lastly, the uncertainty of groundwater risk assessment was analyzed by indicator kriging method. The results meet the decision maker's demand for risk information, and overcome previous risk assessment results expressed in the form of deterministic point estimations, which ignore the uncertainty of risk assessment. PMID- 28987728 TI - Environmental chemicals and breast cancer: An updated review of epidemiological literature informed by biological mechanisms. AB - BACKGROUND: Many common environmental chemicals are mammary gland carcinogens in animal studies, activate relevant hormonal pathways, or enhance mammary gland susceptibility to carcinogenesis. Breast cancer's long latency and multifactorial etiology make evaluation of these chemicals in humans challenging. OBJECTIVE: For chemicals previously identified as mammary gland toxicants, we evaluated epidemiologic studies published since our 2007 review. We assessed whether study designs captured relevant exposures and disease features suggested by toxicological and biological evidence of genotoxicity, endocrine disruption, tumor promotion, or disruption of mammary gland development. METHODS: We systematically searched the PubMed database for articles with breast cancer outcomes published in 2006-2016 using terms for 134 environmental chemicals, sources, or biomarkers of exposure. We critically reviewed the articles. RESULTS: We identified 158 articles. Consistent with experimental evidence, a few key studies suggested higher risk for exposures during breast development to dichlorodiphenyltrichloroethane (DDT), dioxins, perfluorooctane-sulfonamide (PFOSA), and air pollution (risk estimates ranged from 2.14 to 5.0), and for occupational exposure to solvents and other mammary carcinogens, such as gasoline components (risk estimates ranged from 1.42 to 3.31). Notably, one 50-year cohort study captured exposure to DDT during several critical windows for breast development (in utero, adolescence, pregnancy) and when this chemical was still in use. Most other studies did not assess exposure during a biologically relevant window or specify the timing of exposure. Few studies considered genetic variation, but the Long Island Breast Cancer Study Project reported higher breast cancer risk for polycyclic aromatic hydrocarbons (PAHs) in women with certain genetic variations, especially in DNA repair genes. CONCLUSIONS: New studies that targeted toxicologically relevant chemicals and captured biological hypotheses about genetic variants or windows of breast susceptibility added to evidence of links between environmental chemicals and breast cancer. However, many biologically relevant chemicals, including current-use consumer product chemicals, have not been adequately studied in humans. Studies are challenged to reconstruct exposures that occurred decades before diagnosis or access biological samples stored that long. Other problems include measuring rapidly metabolized chemicals and evaluating exposure to mixtures. PMID- 28987729 TI - Enhanced data validation strategy of air quality monitoring network. AB - Quick validation and detection of faults in measured air quality data is a crucial step towards achieving the objectives of air quality networks. Therefore, the objectives of this paper are threefold: (i) to develop a modeling technique that can be used to predict the normal behavior of air quality variables and help provide accurate reference for monitoring purposes; (ii) to develop fault detection method that can effectively and quickly detect any anomalies in measured air quality data. For this purpose, a new fault detection method that is based on the combination of generalized likelihood ratio test (GLRT) and exponentially weighted moving average (EWMA) will be developed. GLRT is a well known statistical fault detection method that relies on maximizing the detection probability for a given false alarm rate. In this paper, we propose to develop GLRT-based EWMA fault detection method that will be able to detect the changes in the values of certain air quality variables; (iii) to develop fault isolation and identification method that allows defining the fault source(s) in order to properly apply appropriate corrective actions. In this paper, reconstruction approach that is based on Midpoint-Radii Principal Component Analysis (MRPCA) model will be developed to handle the types of data and models associated with air quality monitoring networks. All air quality modeling, fault detection, fault isolation and reconstruction methods developed in this paper will be validated using real air quality data (such as particulate matter, ozone, nitrogen and carbon oxides measurement). PMID- 28987730 TI - Excess Lead-210 and Plutonium-239+240: Two suitable radiogenic soil erosion tracers for mountain grassland sites. AB - The expected growing population and challenges associated with globalisation will increase local food and feed demands and enhance the pressure on local and regional upland soil resources. In light of these potential future developments it is necessary to define sustainable land use and tolerable soil loss rates with methods applicable and adapted to mountainous areas. Fallout-radionuclides (FRNs) are proven techniques to increase our knowledge about the status and resilience of agro-ecosystems. However, the use of the Caesium-137 (137Cs) method is complicated in the European Alps due to its heterogeneous input and the timing of the Chernobyl fallout, which occurred during a few single rain events on partly snow covered ground. Other radioisotopic techniques have been proposed to overcome these limitations. The objective of this study is to evaluate the suitability of excess Lead-210 (210Pbex) and Plutonium-239+240 (239+240Pu) as soil erosion tracers for three different grassland management types at the steep slopes (slope angles between 35 and 38 degrees ) located in the Central Swiss Alps. All three FRNs identified pastures as having the highest mean (+/- standard deviation) net soil loss of -6.7 +/- 1.1, -9.8 +/- 6.8 and -7.0 +/- 5.2 Mg ha-1 yr-1 for 137Cs, 210Pbex and 239+240Pu, respectively. A mean soil loss of -5.7 +/- 1.5, -5.2 +/- 1.5 and-5.6 +/- 2.1 was assessed for hayfields and the lowest rates were established for pastures with dwarf-shrubs (-5.2 +/- 2.5, -4.5 +/- 2.5 and 3.3 +/- 2.4 Mg ha-1 yr-1 for 137Cs, 210Pbex and 239+240Pu, respectively). These rates, evaluated at sites with an elevated soil erosion risk exceed the respective soil production rates. Among the three FRN methods used, 239+240Pu appears as the most promising tracer in terms of measurement uncertainty and reduced small scale variability (CV of 13%). Despite a higher level of uncertainty, 210Pbex produced comparable results, with a wide range of erosion rates sensitive to changes in grassland management. 210Pbex can then be as well considered as a suitable soil tracer to investigate alpine agroecosystems. PMID- 28987731 TI - How do measured PBDE and HCBD levels in river fish compare to the European Environmental Quality Standards? AB - This study evaluates the current situation regarding PBDE and HBCD levels in different river fish species. We collected published data in the last five years in different countries around the world. These levels of pollution were compared with Environmental Quality Standards (EQS) for biota established by the European Directive in the field of water policy. Although HBCD situation is not critical, with only some values exceeding the limit about 5 times, the PBDE levels clearly exceeded the established EQS, with 25% of fish samples exceeding up to ten thousand times. Although it is expected that levels of pollution by PBDEs will decrease over the next years due to the ban in their use, it is not expected that this decrease will reach the EQS values by the end of 2021, as demanded by the European Directive. Hence, it is necessary to implement new strategies in order to minimize the impact of PBDEs on the environment. PMID- 28987732 TI - Switch Loop Flexibility Affects Substrate Transport of the AcrB Efflux Pump. AB - The functionally important switch loop of the trimeric multidrug transporter AcrB separates the access and deep drug binding pockets in every protomer. This loop, comprising 11-amino-acid residues, has been shown to be crucial for substrate transport, as drugs have to travel past the loop to reach the deep binding pocket and from there are transported outside the cell via the connected AcrA and TolC channels. It contains four symmetrically arranged glycine residues suggesting that flexibility is a key feature for pump activity. Upon combinatorial substitution of these glycine residues to proline, functional and structural asymmetry was observed. Proline substitutions on the PC1-proximal side completely abolished transport and reduced backbone flexibility of the switch loop, which adopted a conformation restricting the pathway toward the deep binding pocket. Two phenylalanine residues located adjacent to the substitution sensitive glycine residues play a role in blocking the pathway upon rigidification of the loop, since the removal of the phenyl rings from the rigid loop restores drug transport activity. PMID- 28987734 TI - Multifocal lung cancer within ground glass lesions: Are favorable outcomes consequent to surgical resection or inherent to the disease? PMID- 28987735 TI - Endovascular aortic repair of a chronic ascending and arch aortic aneurysm. PMID- 28987736 TI - Atheromatous disease of the aorta and perioperative stroke. PMID- 28987737 TI - Undoing the gaps in quality, cost, and value. PMID- 28987738 TI - Avoiding kidney injury in the surgical patient: Further defining the role of age. PMID- 28987739 TI - Root replacement in acute dissection type A-A superior procedure? PMID- 28987740 TI - Longer-term results, z scores, and decision nomograms for treatment of the ascending aorta in 1693 bicuspid aortic valve operations. AB - OBJECTIVE: This study aims to fine-tune the decision making for ascending aorta treatment in bicuspid aortic valve surgery. METHODS: A total of 1693 patients with a primary indication for aortic valve surgery were investigated retrospectively with respect to a multifactorial decision-making policy including the z score and the clinical outcome in relation to different techniques for ascending aorta treatment (no intervention n = 1116; intervention n = 577 either by ascending aorta replacement n = 404 or aortoplasty n = 173). Follow-up was 99.5% complete (mean 7.0 +/- 4.4 years, range 0-17.7 years, 11,895 patient years). RESULTS: Hospital mortality was 1.2% for the no-intervention group and 0.9% for the intervention group and was not different between groups (P = .629). Survival compared with the adjusted normal population was lower for both groups (no intervention: P < .001) but not by such a great margin for the intervention group (P = .27). Determinants for death were not related to the ascending aorta treatment. Aortoplasty led to significantly more reoperations (P = .002). The z score thresholds for intervention on the ascending aorta were greater for younger patients, intervention was more liberal in young age, depicted in nomograms. CONCLUSIONS: In our study, ascending aorta intervention could be performed with low hospital mortality and obviously did not add to the overall mortality compared with no intervention. Ascending aorta replacement was the most definite intervention. The multifactorial decision for ascending aorta intervention including the z score of the ascending aorta was more liberal in younger patients compared to the simple aortic size guidelines and provided excellent results. However, generalizability needs further data. PMID- 28987733 TI - How Inflammasomes Inform Adaptive Immunity. AB - An immune response consists of a finely orchestrated interplay between initial recognition of potential microbial threats by the innate immune system and subsequent licensed adaptive immune neutralization. The initial recognition integrates environmental cues derived from pathogen-associated molecular patterns and cell-intrinsic damage-associated molecular patterns to contextualize the insult and inform a tailored adaptive response via T and B lymphocytes. While there are much data to support the role of transcriptional responses downstream of pattern recognition receptors in informing the adaptive immune response, markedly less attention has been paid to the role of post-translational responses to pathogen-associated molecular pattern and damage-associated molecular pattern recognition by the innate immune system, and how this may influence adaptive immunity. A well-characterized post-translational consequence of pattern recognition receptor signaling is the assembly of a multimeric signaling platform, termed the inflammasome, by members of the nucleotide-binding oligomerization domain (Nod), leucine-rich repeat-containing receptors (NLRs), and pyrin and HIN domain (PYHIN) families. Inflammasomes assemble in response to cytosolic perturbations, such as mitochondrial dysfunction and aberrant ion fluxes in the case of the canonical NLRP3 inflammasome or the presence of bacterial lipopolysaccharides in the case of the non-canonical inflammasome. Assembly of the inflammasome allows for the cleavage and activation of inflammatory caspases. These activated inflammatory caspases in turn cleave pro form inflammatory cytokines into their mature bioactive species and lead to unconventional protein secretion and lytic cell death. In this review, we discuss evidence for inflammasome-mediated instruction and contextualization of infectious and sterile agents to the adaptive immune system. PMID- 28987741 TI - Diaphragm fenestration for chylothorax: Full of holes? PMID- 28987742 TI - Systematic review of transcatheter aortic valve replacement after previous mitral valve surgery. PMID- 28987743 TI - Is 3-dimensional printing the right fit for your reconstruction? PMID- 28987744 TI - Delirium postcardiac surgery: Intellectual insufficiency and insufficiently understood. PMID- 28987745 TI - Tell it like it is: Experience in mitral valve surgery does matter for improved outcomes in mitral valve infective endocarditis. PMID- 28987746 TI - What type of delirium would you like: Hyperactive, hypoactive, or mixed? None, thanks. PMID- 28987747 TI - Treating locally advanced lung cancer with a 1.5T MR-Linac - Effects of the magnetic field and irradiation geometry on conventionally fractionated and isotoxic dose-escalated radiotherapy. AB - PURPOSE: This study investigates the feasibility and potential benefits of radiotherapy with a 1.5T MR-Linac for locally advanced non-small cell lung cancer (LA NSCLC) patients. MATERIAL AND METHODS: Ten patients with LA NSCLC were retrospectively re-planned six times: three treatment plans were created according to a protocol for conventionally fractionated radiotherapy and three treatment plans following guidelines for isotoxic target dose escalation. In each case, two plans were designed for the MR-Linac, either with standard (~7mm) or reduced (~3mm) planning target volume (PTV) margins, while one conventional linac plan was created with standard margins. Treatment plan quality was evaluated using dose-volume metrics or by quantifying dose escalation potential. RESULTS: All generated treatment plans fulfilled their respective planning constraints. For conventionally fractionated treatments, MR-Linac plans with standard margins had slightly increased skin dose when compared to conventional linac plans. Using reduced margins alleviated this issue and decreased exposure of several other organs-at-risk (OAR). Reduced margins also enabled increased isotoxic target dose escalation. CONCLUSION: It is feasible to generate treatment plans for LA NSCLC patients on a 1.5T MR-Linac. Margin reduction, facilitated by an envisioned MRI guided workflow, enables increased OAR sparing and isotoxic target dose escalation for the respective treatment approaches. PMID- 28987748 TI - Consequences of introducing geometric GTV to CTV margin expansion in DAHANCA contouring guidelines for head and neck radiotherapy. AB - BACKGROUND AND PURPOSE: Defining margins around the Gross Tumour Volume (GTV) to create a Clinical Target Volume (CTV) for head and neck cancer radiotherapy has traditionally been based on presumed knowledge of anatomical routes of spread. However, using a concentric geometric expansion around the GTV may be more reproducible. The purpose of this study was to analyse the inter-observer consistency of geometric CTV delineation with adaptation for anatomical boundaries versus anatomically defined CTVs. MATERIAL AND METHODS: Radiation oncologists at four Danish cancer centres delineated high, intermediate and elective dose CTVs (CTV1, CTV2 and CTV3, respectively) in a patient-case template (stage IV squamous cell carcinoma of the oropharynx), first using mainly anatomical margins (original standard) and then using concentric geometric expansion (new standard). Each centre made a dummy-run radiotherapy plan based on the delineated CTVs. The difference between the CTV contours and the radiotherapy plans was evaluated across the centres. RESULTS: Anatomy-based contours were significantly more heterogenous and showed larger volume differences between centres than geometric margins. Dice similarity coefficient increased by 0.29 and mean surface distance decreased by 4mm for CTV1. Use of consistent CTV volumes resulted in more consistent irradiated volumes between centres. CONCLUSION: Introduction of geometric margins resulted in more uniform CTV1 and CTV2 delineation. Geometric CTV expansion was easier, left less room for misinterpretation, and resulted in more uniform treatment plans with similar irradiated high and intermediate dose volumes across all centres. PMID- 28987749 TI - Different manifestation of irradiation induced coronary artery disease detected with coronary computed tomography compared with matched non-irradiated controls. AB - BACKGROUND AND PURPOSE: Patients who received chest irradiation for treatment of a malignancy are at increased risk for the development of coronary artery atherosclerosis. Little is known about the anatomical coronary artery plaque characteristics of irradiation induced coronary artery disease (CAD). This study aimed to evaluate potential differences in the presence, extent, severity, composition and location of CAD in patients treated with mediastinal irradiation compared with non-irradiated controls matched on age, gender and cardiovascular risk factors. MATERIAL AND METHODS: Seventy-nine asymptomatic Hodgkin and non Hodgkin lymphoma survivors, all treated with mediastinal irradiation with or without chemotherapy, who underwent coronary computed tomography angiography (CTA) to exclude or detect CAD were included. Patients were 1:3 matched with non irradiated controls (n=237) for age, gender, diabetes, hypertension, hypercholesterolemia, family history of CAD and currently smoking. Mean age at cancer diagnosis was 26+/-9years and age at the time of coronary CTA was 45+/ 11years. RESULTS: More patients had an abnormal CTA (defined as any coronary artery atherosclerosis): 59% vs. 36% (P<0.001) and significantly more patients had two vessel CAD: 10% vs. 6% and three vessel/left main CAD: 24% vs. 9% compared with controls (overall P<0.001). The maximum stenosis severity among patients was less often <30% (53% vs. 68%) and more often >70% (7% vs. 0%) (overall P=0.001). Patients had more coronary artery plaques in proximal coronary artery segments: left main (17% vs. 6%, P=0.004), proximal left anterior descending artery (30% vs. 16%, P=0.004), proximal right coronary artery (25% vs 10%, P<0.001) and proximal left circumflex artery (14% vs 6%, P=0.022), whereas the number of plaques in non-proximal segments did not differ between groups. CONCLUSIONS: Hodgkin and non-Hodgkin lymphoma survivors treated with mediastinal irradiation with or without chemotherapy showed a higher presence, greater severity, larger extent and more proximally located CAD compared with age, gender and risk factor matched non-irradiated controls. These findings represent features of higher risk CAD and may explain the worse cardiovascular outcome after chest irradiation. PMID- 28987750 TI - Metabolic risk profiles in diabetes stratified according to age at onset, islet autoimmunity and fasting C-peptide. AB - OBJECTIVE: Islet autoimmunity, age at onset and time to insulin treatment are often used to define subgroups of diabetes. However, the latter criterion is not clinical useful. Here, we examined whether an unbiased stratification of diabetes according to age at onset, fasting C-peptide and GAD autoantibodies (GADab) defines groups with differences in glycaemic control and markers of cardiometabolic risk. DESIGN AND METHODS: A cohort of 4374 adults with relatively newly diagnosed diabetes referred to a Danish hospital during 1997-2012 was stratified according to age at onset above or below 30 years, fasting C-peptide above or below 300 pmol/l (CPEPhigh or CPEPlow), and presence or absence of GADab (GADpos or GADneg). HbA1c, BMI, blood pressure (BP), lipid profile, alanine aminotransferase (ALT) and creatinine were evaluated. RESULTS: GADab were present in 13% of the cohort. Age at onset was not associated with major differences between groups. Patients with insulin deficient diabetes (CPEPlow; n = 503) had higher HbA1c but otherwise lower cardiometabolic risk (lower BMI, BP, LDL, triacylglycerol, and ALT, and higher HDL) than both patients with latent autoimmune diabetes of adults (LADA defined as GADposCPEPhigh; n = 327) and patients with type 2 diabetes (GADnegCPEPhigh; n = 3544). Patients with LADA defined an intermediate group with higher HbA1c but otherwise lower cardiometabolic risk than patients with type 2 diabetes. CONCLUSIONS: Our results demonstrate that fasting C-peptide and GADab status, but not age at onset, define groups of patients with diabetes with clinically relevant differences in glycaemic control and cardiometabolic risk. PMID- 28987751 TI - Childhood Obesity and Physical Activity-Friendly School Environments. AB - OBJECTIVE: Childhood obesity may be related to school environment, but previous studies often focused on food environment only. This study aimed to examine the relationship between school physical activity environment and childhood obesity. STUDY DESIGN: This is a cross-sectional study with multilevel data collected on school physical activity environment using teacher questionnaires, students' growth, and obesity status from electronic health records, and neighborhood socioeconomic status from census data. RESULTS: This study included 208 280 students (6-18 years of age) from 438 schools (45% of Hong Kong). Prevalence of obesity was 5.0%. After controlling for socioeconomic status and intraschool correlation, robust Poisson regression revealed a reduced obesity risk associated with higher teachers' perceived physical activity benefits (risk ratio 0.96, 95% CI 0.94-0.99, P = .02), physical activity teaching experience (0.93, 0.91-0.96, P < .001), school campus size (0.93, 0.87-0.99, P = .02), physical activity ethos (0.91, 0.88-0.94, P < .001), number of physical activity programs (0.93, 0.90 0.96, P < .001), and physical activity facilities (0.87, 0.84-0.90, P < .001). Students in schools with at least 3 physical activity-friendly environmental factors (11.7%) had a much lower risk of obesity (0.68, 0.62-0.75, P < .001) than those without (23.7%). CONCLUSIONS: A physical activity-friendly school environment is associated with lower risk of obesity. School physical activity environment should be considered in future epidemiologic and intervention studies. PMID- 28987752 TI - Three Cases of KCNT1 Mutations: Malignant Migrating Partial Seizures in Infancy with Massive Systemic to Pulmonary Collateral Arteries. AB - KCNT1 mutations are gain-of-function mutations in potassium channels resulting in severe infantile epilepsy. Herein we describe 3 infants with malignant migrating partial seizures with KCNT1 mutations accompanied by massive systemic to pulmonary collateral arteries with life-threatening hemoptysis and heart failure. PMID- 28987753 TI - Prospective Evaluation of Physical Contact with Critically Ill Child on Caregiver Spiritual Wellbeing. AB - OBJECTIVES: To evaluate whether a pediatric intensive care unit initiative promoting physical contact between caregiver and patient improves caregiver spiritual wellbeing. The secondary objectives were to evaluate caregiver perceptions of care before and after the initiative and to follow unplanned extubation rate as a marker of safety of the initiative. We hypothesized that caregiver spiritual wellbeing and caregiver perceptions of care would improve with implementation of our physical contact initiative known as Project ROSE (Reach Out, Soothe, and Embrace). STUDY DESIGN: Project ROSE was a practice change initiative promoting physical contact between caregiver and hospitalized child in an academic quaternary care pediatric intensive care unit. Caregivers' spiritual wellbeing and perceptions of care were surveyed at days 1 and 4, then compared pre- and postimplementation of the unit-wide initiative. Wilcoxon rank sum tests compared groups (pre- and post-Project ROSE). A total of 331 caregivers returned surveys. RESULTS: We analyzed 331 surveys (pre, n = 174/post, n = 157). Caregiver spiritual wellbeing at enrollment (day 1) was no different between groups (P = .47). Caregiver spiritual wellbeing on day 4 was greater in the postintervention group (pre 40.0 [32.0, 44.0] vs post 42.0 [37.5, 45.0] P = .03). Caregiver perceptions of care improved postintervention. There was no change in the unplanned extubation rate between groups. CONCLUSION: Project ROSE improved caregiver spiritual wellbeing and perceptions of care, was implemented safely, addresses a need in family-centered care of critically ill pediatric patients, and merits consideration for integration into practice. PMID- 28987754 TI - A Rare Cause of Post-Sphincterotomy Bleeding. PMID- 28987755 TI - A 45-Year-Old Man With Recurrent Nausea, Vomiting, and Abdominal Distension. PMID- 28987756 TI - Severe Esophageal Dysphagia, Weight Loss, and Atrial Fibrillation: A Devastating Outcome. PMID- 28987757 TI - Double-Bubble Sign in an Adult Patient. PMID- 28987758 TI - A Long-Lasting Dysphagia. PMID- 28987759 TI - A Rare Hypervascular Mass in the Uncinate Process of the Pancreas. PMID- 28987760 TI - Multiple Openings in the Anterior Abdominal Wall Draining Pus for a Decade. PMID- 28987761 TI - Complication of Button Battery Ingestion. PMID- 28987762 TI - Protective outcomes of low-dose doxycycline on renal function of Wistar rats subjected to acute ischemia/reperfusion injury. AB - Renal ischemia-reperfusion injury (IRI) is a major cause of acute renal failure. Doxycycline (Dc) belongs to the tetracycline-class of antibiotics with demonstrated beneficial molecular effects in the brain and heart, mainly through matrix metalloproteinases inhibition (MMP). However, Dc protection of renal function has not been demonstrated. We determined whether low doses of Dc would prevent decreases in glomerular filtration rate (GFR) and maintain tubular Na+ handling in Wistar rats subjected to kidney I/R. Male Wistar rats underwent bilateral kidney ischemia for 30min followed by 24h reperfusion (I/R). Doxycycline (1, 3, and 10mg/kg, i.p.) was administered 2h before surgery. Untreated I/R rats showed a 250% increase in urine volume and proteinuria, a 60% reduction in GFR, accumulation of urea-nitrogen in the blood, and a 60% decrease in the fractional Na+ excretion due to unbalanced Na+ transporter activity. Treatment with Dc 3mg/kg maintained control levels of urine volume, proteinuria, GFR, blood urea-nitrogen, fractional Na+ excretion, and equilibrated Na+ transporter activities. The Dc protection effects on renal function were associated with kidney structure preservation and prevention of TGFbeta and fibronectin deposition. In vitro, total MMP activity was augmented in I/R and inhibited by 25 and 50MUM Dc. In vivo, I/R augmented MMP-2 and -9 protein content without changing their activities. Doxycycline treatment downregulated total MMP activity and MMP-2 and -9 protein content. Our results suggest that treatment with low dose Dc protects from IRI, thereby preserving kidney function. PMID- 28987763 TI - Endogenous osteopontin induces myocardial CCL5 and MMP-2 activation that contributes to inflammation and cardiac remodeling in a mouse model of chronic Chagas heart disease. AB - Cardiac dysfunction with progressive inflammation and fibrosis is a hallmark of Chagas disease caused by persistent Trypanosoma cruzi infection. Osteopontin (OPN) is a pro-inflammatory cytokine that orchestrates mechanisms controlling cell recruitment and cardiac architecture. Our main goal was to study the role of endogenous OPN as a modulator of myocardial CCL5 chemokine and MMP-2 metalloproteinase, and its pathological impact in a murine model of Chagas heart disease. Wild-type (WT) and OPN-deficient (spp1 -/-) mice were parasite-infected (Brazil strain) for 100days. Both groups developed chronic myocarditis with similar parasite burden and survival rates. However, spp1 -/- infection showed lower heart-to-body ratio (P<0.01) as well as reduced inflammatory pathology (P<0.05), CCL5 expression (P<0.05), myocyte size (P<0.05) and fibrosis (P<0.01) in cardiac tissues. Intense OPN labeling was observed in inflammatory cells recruited to infected heart (P<0.05). Plasma concentration of MMP-2 was higher (P<0.05) in infected WT than in spp1 -/- mice. Coincidently, specific immunostaining revealed increased gelatinase expression (P<0.01) and activity (P<0.05) in the inflamed hearts from T. cruzi WT mice, but not in their spp1 -/- littermates. CCL5 and MMP-2 induction occurred preferentially (P<0.01) in WT heart-invading CD8+ T cells and was mediated via phospho-JNK MAPK signaling. Heart levels of OPN, CCL5 and MMP-2 correlated (P<0.01) with collagen accumulation in the infected WT group only. Endogenous OPN emerges as a key player in the pathogenesis of chronic Chagas heart disease, through the upregulation of myocardial CCL5/MMP-2 expression and activities resulting in pro inflammatory and pro-hypertrophic events, cardiac remodeling and interstitial fibrosis. PMID- 28987764 TI - Comparing the effects of adapting to a weight on one leg during treadmill and overground walking: A pilot study. AB - BACKGROUND: Locomotor adaptation has been suggested as a way to improve gait symmetry in individuals post-stroke. Most perturbation methods utilize costly, specialized equipment. The use of a unilateral leg weight may provide a low cost, clinically translatable alternative. Furthermore, previous studies have suggested that adaptation context may affect movement outcomes. The purpose of this study was to assess the ability of a unilaterally applied ankle weight to drive locomotor adaptation and determine the effect of context (treadmill versus overground) in young, non-disabled participants. METHODS: Eighteen young non disabled adults were randomly assigned to receive 10min of walking on a treadmill with a weight (TG), overground with a weight (OG) or as a control on a treadmill/overground without a weight (CG). Outcomes measured before, during and after adaptation were: step length symmetry, single limb support symmetry and gait speed. RESULTS: After adding the weight, single limb support immediately became asymmetrical for all participants without changes in step length symmetry. After walking for 10min, TG step length became asymmetrical. After weight removal, both TG and OG had increased step length asymmetry. TG decreased single limb support asymmetry while OG did not. After walking overground without the weight, walking parameters eventually returned to baseline in both weighted groups. The control group showed no changes. CONCLUSION: A unilaterally applied ankle weight appears able to cause gait adaptation in young, non-disabled participants. However different adaptive changes in the gait pattern are made by the nervous system when the perturbation is applied in different contexts. PMID- 28987765 TI - Impaired perceived timing of falls in the elderly. AB - Falls are the leading cause of injury-related deaths and hospitalizations, with older adults at an increased risk. As humans age, physical changes and health conditions make falls more likely. While we know how the body reflexively responds to prevent injury during a fall, we know little about how people perceive the fall itself. We previously found that young adults required a fall to precede a comparison sound stimulus by approximately 44ms to perceive the two events as simultaneous. This may relate to common anecdotal reports suggesting that humans often describe distortions in their perception of time - time seems to slow down during a fall - with very little recollection of how and when the fall began. Here we examine whether fall perception changes with age. Young (19 25y) and older (61-72y) healthy adults made temporal order judgments identifying whether the onset of their fall or the onset of a comparison sound came first to measure the point of subjective simultaneity. Results show that fall perception is nearly twice as slow for older adults, where perturbation onset has to precede sound onset by ~88ms to appear coincident, compared to younger adults (~44ms). We suggest that such age-related differences in fall perception may relate to increased fall rates in older adults. We conclude that a better understanding of how younger versus older adults perceive falls may identify important factors for innovative fall prevention strategies and rehabilitative training exercises to improve fall awareness. PMID- 28987766 TI - Nervous system excitability and joint stiffness following short-term dynamic ankle immobilization. AB - Joint immobilization has been demonstrated to modify neural excitability in subsets of healthy populations, leading to disinhibition of cortical and reflexive pathways. However, these findings may have limited clinical application as most models have investigated casting and rigid immobilization, while many musculoskeletal injuries often utilize dynamic immobilization devices such as boot immobilizers and pneumatic splints that allow for modified ambulation. We therefore aimed to determine the short-term effects of ambulation in ankle immobilization devices on nervous system excitability and stiffness in able bodied individuals. A repeated-measures design was implemented where 12 healthy individuals were tested for cortical excitability to the ankle musculature using transcranial magnetic stimulation, reflexive excitability using the Hoffmann reflex, and ankle joint stiffness using arthrometry before and after 30min of ambulation with a boot immobilizer, pneumatic leg splint, or barefoot. Motor evoked potential (MEP), cortical silent period (CSP), Hmax to Mmax ratio, and ankle joint displacement were extracted as dependent variables. Results indicated that despite the novel motor demands of walking in immobilization devices, no significant changes in cortical excitability (F>=0.335, P>=0.169), reflexive excitability (F>=0.027, P>=0.083), or joint stiffness (F>=0.558, P>=0.169) occurred. These findings indicate that short-term ambulation in dynamic immobilization devices does not modify neural excitability despite forced constraints on the sensorimotor system. We may therefore conclude that modifications to neural excitability in previous immobilization models are mediated by long-term nervous system plasticity rather than acute mechanisms, and there appear to be no robust changes in corticomotor or spinal excitability acutely posed by ambulation with immobilization devices. PMID- 28987767 TI - Effects of high-heeled footwear on static and dynamic pelvis position and lumbar lordosis in experienced younger and middle-aged women. AB - There is still conflicting evidence about the effect of high-heeled footwear on posture, especially if methodological confounders are taken into account. The purpose of this study was to investigate the effect of high-heeled footwear on lumbopelvic parameters in experienced younger and middle-aged women while standing and walking. Thirty-seven experienced younger (n=19:18-25 years) and middle-aged (n=18:26-56 years) women were included in this randomized crossover study. Using a non-invasive back shape reconstruction device (rasterstereography), static (pelvic tilt and lumbar lordosis angle) and dynamic (pelvic rotation, median lumbar lordosis angle and range of motion) parameters representing pelvis position and lumbar curvature were measured. In order to analyse standing and walking on a treadmill (0.83m/s), the effects of high-heels (7-11cm) were compared to standard control shoes. There were no effects on the lumbar lordosis angle or range of motion under static or dynamic conditions (p>0.05, d<=0.06). But there was a small effect for a reduced pelvic tilt (p=0.003, d=0.24) and a moderate effect for an increased transversal pelvic rotation (p=0.001, d=0.63) due to high heel shoed standing or walking, respectively. There were no significant age-group or interaction effects (p>0.05). Altered pelvic parameters may be interpreted as compensatory adaptations to high-heeled footwear rather than lumbar lordosis adaptations in experienced wearers. The impact of these findings on back complaints should be revisited carefully, because muscular overuse as well as postural load relieving may contribute to chronic consequences. Further research is necessary to examine clinically relevant outcomes corresponding to postural alterations. PMID- 28987768 TI - Patient-reported outcomes in KEYNOTE-006, a randomised study of pembrolizumab versus ipilimumab in patients with advanced melanoma. AB - OBJECTIVE: Report results of patient-reported health-related quality of life (HRQoL) and symptoms from phase III KEYNOTE-006 study of pembrolizumab versus ipilimumab in patients with ipilimumab-naive advanced melanoma. PATIENTS AND METHODS: Patients received pembrolizumab 10 mg/kg every 2 (Q2W) or every 3 weeks (Q3W) for up to 2 years, or four cycles of ipilimumab 3 mg/kg Q3W. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) was administered at baseline and throughout the study. Patient-reported outcome (PRO) analyses were pre-specified exploratory endpoints; the primary PRO assessment was the score change from baseline to week 12 in EORTC QLQ-C30 global health status (GHS)/HRQoL score between the arms using constrained longitudinal data analysis. RESULTS: The PRO analysis population included 776 patients: pembrolizumab Q2W (n = 270); pembrolizumab Q3W (n = 266); ipilimumab (n = 240). Baseline GHS was similar across arms. QLQ-C30 compliance rates at week 12 were 87% (n = 214), 97% (n = 226), and 96% (n = 178), for the pembrolizumab Q2W, pembrolizumab Q3W, and ipilimumab arms, respectively. From baseline to week 12, GHS/HRQoL scores were better maintained with pembrolizumab than with ipilimumab (decrease of -1.9 and -2.5 for pembrolizumab versus -10.0 for ipilimumab; p < 0.001 for each pembrolizumab arm versus ipilimumab). Fewer patients treated with pembrolizumab experienced deterioration in GHS at week 12 (31% for pembrolizumab Q2W; 29% for Q3W and 44% for ipilimumab), with similar trends observed for individual functioning and symptoms scales. CONCLUSIONS: HRQoL was better maintained with pembrolizumab than with ipilimumab in patients with ipilimumab naive advanced melanoma. CLINICALTRIALS. GOV IDENTIFIER: NCT01866319. PMID- 28987769 TI - Insight in taste alterations during treatment with protein kinase inhibitors. AB - The role of Protein Kinase Inhibitors (PKI) in the treatment of various types of cancer is increasingly prominent. Their clinical application is accompanied by the development of side effects, among which patient-reported taste alterations. These alterations are missed frequently, but impair nutritional intake, are associated with weight loss and often result in significant morbidity, especially in the context of chronic administration. Accurate reporting of taste alterations is hampered by lack of modules for symptom objectification and inadequate understanding on the underlying mechanisms. In this review we initially describe the physiology of taste and smell and the mechanism of action of PKIs. We proceed to summarize taste related side effects as reported in major clinical trials and describe possible causal factors. Lastly, an in-depth analysis is given on potential molecular pathways responsible for the PKI-induced taste alterations. Objectification of patient-reported symptoms and universal reporting, along with a better understanding of the underlying mechanisms, will lead to early recognition and optimized treatment, ultimately improving patient adherence and quality of life. PMID- 28987770 TI - Prognostic scores for sorafenib-treated hepatocellular carcinoma patients: A new application for the hepatoma arterial embolisation prognostic score. AB - BACKGROUND: No prognostic classification is currently used for patients treated with systemic therapies for Hepatocellular Carcinoma (HCC). METHODS: We retrospectively analysed data from patients treated with sorafenib for HCC from five centres in France and in the United Kingdom (UK). The training set comprised data from two centres and the validation set from three. Variables independently associated with Overall Survival (OS) in the training set were used to build the SAP (Sorafenib Advanced HCC Prognosis) score. The score was tested in the validation set, then compared with other prognostication systems. RESULTS: The training set and validation set included 370 and 468 patients respectively. In the training set, variables independently associated with OS in multivariable analysis were: performance status (PS) >0, alpha-fetoprotein (AFP) >400 ng/ml, tumour size >7 cm, bilirubin >17 MUmol/l and albumin <36 g/l. The SAP score was built giving one point to each abnormal variable, and three classes were constructed. The SAP score was significantly associated with OS in the training set, with median OS of 14.9 months for SAP A, 7.2 months for SAP B and 2.5 months for SAP C (P < 0.001). In the validation set, the SAP score was significantly associated with OS, and showed greater discriminative abilities than Barcelona Clinic Liver Cancer (BCLC) and albumin-bilirubin (ALBI) scores. However, the hepatoma arterial embolisation prognostic (HAP) score showed greater discriminative abilities than the SAP score. CONCLUSION: In European patients treated with sorafenib, the HAP was the most discriminant prognostic score and may facilitate stratification in trials and inform clinical decision making. PMID- 28987771 TI - 'Mind the gap' between the development of therapeutic innovations and the clinical practice in oncology: A proposal of the European Organisation for Research and Treatment of Cancer (EORTC) to optimise cancer clinical research. AB - In Europe, most of the cancer clinical research dedicated to therapeutic innovations aims primarily at regulatory approval. Once an anticancer drug enters the common market, each member state determines its real-world use based on its own criteria: pricing, reimbursement and clinical indications. Such an innovation centred clinical research landscape might neglect patient-relevant issues in real world setting, such as comparative effectiveness of distinct treatment options or long-term safety monitoring. The European Organisation for Research and Treatment of Cancer (EORTC) advocates reforming the current 'innovation-centred' system to a truly 'patient-centred' paradigm with systematically coordinated applied clinical research in conjunction with drug development, featuring the following strategy. PMID- 28987772 TI - Relationship between margin of stability and deviations in spatiotemporal gait features in healthy young adults. AB - Increased variability of spatio-temporal features while walking is related to increased risk of falls. It is thought that variability in foot placement and timing reflects responses to mechanical instability while walking. The purpose of this study was to determine whether 'extreme' values of step length, width and time follow transient periods of low mechanical stability during the single support phase of gait in healthy young adults. We conducted secondary analysis of a portion of an existing dataset. Eleven healthy adults walked on an instrumented treadmill. Participants were outfitted with reflective markers and completed two 1-min periods of walking at each of 3 speeds (0.8m/s, 1.2m/s, and 1.6m/s). Margins of stability were calculated relative to the anterior, posterior, lateral, and medial boundaries of the base of support, and the value at heel strike and the minimum value during the first half of each single-support phase were extracted. Step length, swing time, and step width were calculated from motion capture and ground reaction force data. Extreme values for consecutive steps were identified using Poincare plots, and margins of stability in each direction were compared between 'normal' and 'extreme' steps. Margins of stability in both the anterior and medial direction were lower prior to long and wide steps, respectively. Margins of stability in the anterior and medial directions were lower prior to quick steps, and margins of stability in the posterior and lateral directions were lower prior to slow steps. There were either no significant differences in margin of stability between 'normal' and 'extreme' steps at heel strike, or the direction of the relationship was reversed to that observed during single support. These data suggest that spatio-temporal variability may reflect adjustments in step placement and timing to compensate for transient periods of low mechanical stability when walking. PMID- 28987773 TI - Effects of temperature, soil moisture and photoperiod on diapause termination and post-diapause development of the wheat blossom midge, Sitodiplosis mosellana (Gehin) (Diptera: Cecidomyiidae). AB - Sitodiplosis mosellana, one of the most important wheat pests, goes through larval diapause in a cocooned form. It is univoltine, but some individuals exhibit prolonged diapause. In this study, we documented diapause termination rate of cocooned larvae at different diapausing periods and time required for adult emergence when they were brought to 25 degrees C from the field in northern China. We found that field larvae all entered diapause by June, but none terminated diapause until late September when the daily average temperature dropped to below 20 degrees C. Furthermore, termination rate increased significantly as diapausing larvae underwent increasing chilling duration, reaching >95% from early December to early March. Our results suggest that chilling was necessary for diapause to terminate and that field diapause termination ended in early December. To explore low temperature and duration required, we cold-treated field diapausing larvae of different periods at different low temperatures for various lengths of time prior to the 25 degrees C incubation. Chilling at 4-8 degrees C for 60-90days resulted in a higher termination rate (>90%) and shorter adult emergence time in general. Additionally, we investigated the combined effect of temperature (18-30 degrees C) and soil moisture (20-60%, on dry weight basis) as well as the effect of photoperiod (24:0-0:24L:D) on post-diapause development. While photoperiod did not affect adult emergence, soil moisture ranging from 30 to 50% and temperature from 22 to 26 degrees C resulted in the highest adult emergence rates (>46%) within relatively short time (<18days). Mortality and/or prolonged diapause rate drastically increased when incubation conditions were outside the optimal range, especially at 30 degrees C. These findings provide new insight into the diapause process of S. mosellana, and information will be useful for development of field forecasting and laboratory rearing techniques of this pest insect. PMID- 28987774 TI - Cell membrane permeability coefficients determined by single-step osmotic shift are not applicable for optimization of multi-step addition of cryoprotective agents: As revealed by HepG2 cells. AB - HepG2 cells have a number of research applications and cryopreservation of these cells would improve supply and thus facilitate the study. Development of effective cryopreservation protocols relies on knowledges of the fundamental mass transport characteristics of HepG2 cell membrane. Currently, the permeability parameters estimated from single-step addition are routinely used to predict the osmotic responses of the cells in multistep protocols, as well as used for prediction of optimal cooling rates. However, the reasonability of this approach has not been rigorously studied. Here we measured the hydraulic conductivity (Lp) and the permeability coefficient (Ps) of HepG2 cells in the absence/presence of dimethyl sulfoxide (Me2SO) at various temperatures with single and multistep addition of Me2SO. We found that the permeability yielded via one-step addition of the Me2SO cannot exactly predict the volume change of the cells when the CPA was added in multiple steps. PMID- 28987775 TI - Slow freezing versus vitrification technique for human ovarian tissue cryopreservation: An evaluation of histological changes, WNT signaling pathway and apoptotic genes expression. AB - This study compared slow freezing and vitrification of ovarian tissue by evaluation of histological changes, WNT signaling pathway and apoptotic genes expression. Ovarian tissue was obtained from women aging 27-38 years old. Ovarian cortex from each patient was divided into three pieces and randomly grouped as slow freezing, vitrification and control groups for investigation of WNT signaling gene expression and beta-CATENIN presence as well as histological studies. The stromal structure of all ovaries were preserved. The number of secondary follicles decreased in vitrified group (P < 0.05). WNT-3, beta-CATENIN, FZD-2 and GSK-3beta expressions were significantly higher in slow frozen and vitrified groups, compared to control group (P < 0.05). On the contrary, AXIN1 expression in slow frozen samples were significantly lower than that of the vitrified and control group. The expression of apoptotic genes, excluding CASP3, was significantly decreased in slow-frozen samples (P < 0.05). Conversely, BAX:BCL-2 percentage significantly increased in vitrification versus slow freezing and control(P < 0.05). Follicles in slow frozen samples displayed nuclear and cytoplasmic beta-CATENIN staining, while control and vitrification groups only showed beta-CATENIN protein in the cytoplasm. The presented data show that slow freezing results in a better preservation regardless of the type of follicle. Therefore, it is concluded that slow freezing is still an ideal method for ovary cryopreservation. PMID- 28987776 TI - Bile acid profiles in neonatal intrahepatic cholestasis caused by citrin deficiency. AB - BACKGROUND: Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is characterized by conjugated hyperbilirubinemia and increased plasma bile acid concentrations. However, the underlying mechanisms remain unclear. We established a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for simultaneously quantifying plasma bile acids and examined bile acid profiles in NICCD infants. METHODS: We measured 15 bile acids within 15min and found a wide linear range for individual bile acids. RESULTS: The within-run and run-to-run CV of all bile acids was 1.2-10.9% and 3.1-10.8%, respectively, with a mean recovery of 90.5-112.6%. Compared to infants with citrullinemia without mutations in SLC25A13 (non-NICCD), NICCD infants showed increased plasma total bile acid concentrations (mean: 201 vs. 42MUM, p<0.001), with a distinct bile acid profile characterized by increased conjugated primary bile acid concentrations. The calculated ratios, including primary/secondary bile acid (714 vs. 235, p<0.05) and conjugated/free bile acid (371 vs. 125, p<0.05) ratios, were higher in NICCD infants. The area under receiver operating characteristic curve for conjugated/free bile acid ratio to identify infants with NICCD was 0.871 (95% confidence interval, 0.713-1.0). CONCLUSIONS: Together, our findings indicated plasma bile acid profile as a potential noninvasive diagnostic biomarker for NICCD. PMID- 28987777 TI - Palestinian Arab ethnicity is associated with an adverse metabolic phenotype. AB - Urban-dwelling Palestinians have been shown to have higher cardiovascular morbidity and mortality and prevalence of diabetes than urban Israelis. Inflammation is implicated in the etiology of these conditions. We hypothesized that increased inflammatory activation, manifested as increased GlycA, a novel biomarker of global inflammation, would be evident in Palestinians. We compared GlycA concentrations between Palestinians and Israelis and assessed the associations of GlycA with anthropometric, health behavioral and clinical variables in a sample of 1674 Palestinians and Israelis aged 25-74, residing in Jerusalem. The main outcome measure was GlycA concentration. GlycA was higher in Palestinians than Israelis (p<0.001). This finding persisted in young Palestinians with normal glucose tolerance. GlycA, total white blood cell count, the triglyceride to HDL-cholesterol ratio and small LDL-cholesterol particles were all significantly higher in Palestinians compared to Israelis across obesity and glucose tolerance categories. Palestinian women had greater GlycA compared to Israeli women and men of both ethnicities. GlycA as well as adverse cardiovascular biomarkers are all higher in Palestinian Arabs than Israeli Jews, even in young healthy adults. This propensity to inflammation may be a driver of the higher risk of cardiovascular disease, insulin resistance and diabetes observed in this population. PMID- 28987778 TI - Erratum to "Emission inventory of primary air pollutants in 2010 from industrial processes in Turkey" [Sci. Total Environ. 488-489 (2014) 369-381]. PMID- 28987779 TI - Thyroid hormone- and estrogen receptor interactions with natural ligands and endocrine disruptors in the cerebellum. AB - Although the effects of phytoestrogens on brain function is widely unknown, they are often regarded as "natural" and thus as harmless. However, the effects of phytoestrogens or environmental pollutants on brain function is underestimated. Estrogen (17beta-estradiol, E2) and thyroid hormones (THs) play pivotal roles in brain development. In the mature brain, these hormones regulate metabolism on cellular and organismal levels. Thus, E2 and THs do not only regulate the energy metabolism of the entire organism, but simultaneously also regulate important homeostatic parameters of neurons and glia in the CNS. It is, therefore, obvious that the mechanisms through which these hormones exert their effects are pleiotropic and include both intra- and intercellular actions. These hormonal mechanisms are versatile, and the experimental investigation of simultaneous hormone-induced mechanisms is technically challenging. In addition, the normal physiological settings of metabolic parameters depend on a plethora of interactions of the steroid hormones. In this review, we discuss conceptual and experimental aspects of the gonadal and thyroid hormones as they relate to in vitro models of the cerebellum. PMID- 28987780 TI - Different levels of visual perceptual skills are associated with specific modifications in functional connectivity and global efficiency. AB - The disembedding ability (i.e., the ability to identify a simple masked figure within a complex one) depends on attentional mechanisms, executive functions and working memory. Recent cognitive models ascribed different levels of disembedding task performance to the efficiency of the subtended mental processes engaged during visuo-spatial perception. Here we aimed at assessing whether different levels of the disembedding ability were associated to the functional signatures of neural efficiency, defined as a specific modulation in response magnitude and functional connectivity strength in task-related areas. Consequently, brain activity evoked by a visual task involving the disembedding ability was acquired using functional magnetic resonance imaging (fMRI) in a sample of 23 right-handed healthy individuals. Brain activity was analyzed at different levels of information processing, from local responses to connectivity interactions between brain nodes, as far as to network topological properties. All different levels of information processing were significantly modulated by individual behavioral performance. Specifically, single voxel response magnitude, connectivity strength of the right intrahemispheric and interhemispheric edges, and graph measures (i.e., local and global efficiency) were negatively associated to behavioral performance. Altogether, these results indicate that efficiency during a disembedding task cannot be merely attributed to a reduced neural recruitment of task-specific regions, but can be better characterized as an enhanced functional hemispherical asymmetry. PMID- 28987781 TI - How prokaryotes 'encode' their environment: Systemic tools for organizing the information flow. AB - An important issue related to code biology concerns the cell's informational relationships with the environment. As an open self-producing system, a great variety of inputs and outputs are necessary for the living cell, not only consisting of matter and energy but also involving information flows. The analysis here of the simplest cells will involve two basic aspects. On the one side, the molecular apparatuses of the prokaryotic signaling system, with all its variety of environmental signals and component pathways (which have been called 1 2-3 Component Systems), including the role of a few second messengers which have been pointed out in bacteria too. And in the other side, the gene transcription system as depending not only on signaling inputs but also on a diversity of factors. Amidst the continuum of energy, matter, and information flows, there seems to be evidence for signaling codes, mostly established around the arrangement of life-cycle stages, in large metabolic changes, or in the relationships with conspecifics (quorum sensing) and within microbial ecosystems. Additionally, and considering the complexity growth of signaling systems from prokaryotes to eukaryotes, four avenues or "roots" for the advancement of such complexity would come out. A comparative will be established in between the signaling strategies and organization of both kinds of cellular systems. Finally, a new characterization of "informational architectures" will be proposed in order to explain the coding spectrum of both prokaryotic and eukaryotic signaling systems. Among other evolutionary aspects, cellular strategies for the construction of novel functional codes via the intermixing of informational architectures could be related to the persistence of retro-elements with obvious viral ancestry. PMID- 28987782 TI - Development of magnesium-based biodegradable metals with dietary trace element germanium as orthopaedic implant applications. AB - : From the perspective of element biosafety and dietetics, the ideal alloying elements for magnesium should be those which are essential to or naturally presented in human body. Element germanium is a unique metalloid in the carbon group, chemically similar to its group neighbors, Si and Sn. It is a dietary trace element that naturally presents in human body. Physiological role of Ge is still unanswered, but it might be necessary to ensure normal functioning of the body. In present study, novel magnesium alloys with dietary trace element Ge were developed. Feasibility of those alloys to be used as orthopaedic implant applications was systematically evaluated. Mg-Ge alloys consisted of alpha-Mg matrix and eutectic phases (alpha-Mg + Mg2Ge). Mechanical properties of Mg-Ge alloys were comparable to current Mg-Ca, Mg-Zn and Mg-Sr biodegradable metals. As rolled Mg-3Ge alloy exhibited outstanding corrosion resistance in vitro (0.02 mm/y, electrochemical) with decent corrosion rate in vivo (0.6 mm/y, in rabbit tibia). New bone could directly lay down onto the implant and grew along its surface. After 3 months, bone and implant were closely integrated, indicating well osseointegration being obtained. Generally, this is a pioneering study on the in vitro and in vivo performances of novel Mg-Ge based biodegradable metals, and will benefit the future development of this alloy system. STATEMENT OF SIGNIFICANCE: The ideal alloying elements for magnesium-based biodegradable metals should be those which are essential to or naturally presented in human body. Element germanium is a unique metalloid in the carbon group. It is a dietary trace element that naturally presents in human body. In present study, feasibility of Mg-Ge alloys to be utilized as orthopedic applications was systematically investigated, mainly focusing on the microstructure, mechanical property, corrosion behavior and biocompatibility. Our findings showed that Mg 3Ge alloy exhibited superior corrosion resistance to current Mg-Ca, Mg-Zn and Mg Sr alloys with favorable biocompatibility. This is a pioneering study on the in vitro &in vivo performances of Mg-Ge biodegradable metals, and will benefit the future development of this alloy system. PMID- 28987783 TI - Engineering fibrin hydrogels to promote the wound healing potential of mesenchymal stem cell spheroids. AB - : Mesenchymal stem cells (MSCs) secrete endogenous factors such as vascular endothelial growth factor (VEGF) and prostaglandin E2 (PGE2) that promote angiogenesis, modulate the inflammatory microenvironment, and stimulate wound repair, and MSC spheroids secrete more trophic factors than dissociated, individual MSCs. Compared to injection of cells alone, transplantation of MSCs in a biomaterial can enhance their wound healing potential by localizing cells at the defect site and upregulating trophic factor secretion. To capitalize on the therapeutic potential of spheroids, we engineered a fibrin gel delivery vehicle to simultaneously enhance the proangiogenic and anti-inflammatory potential of entrapped human MSC spheroids. We used multifactorial statistical analysis to determine the interaction between four input variables derived from fibrin gel synthesis on four output variables (gel stiffness, gel contraction, and secretion of VEGF and PGE2). Manipulation of the four input variables tuned fibrin gel biophysical properties to promote the simultaneous secretion of VEGF and PGE2 by entrapped MSC spheroids while maintaining overall gel integrity. MSC spheroids in stiffer gels secreted the most VEGF, while PGE2 secretion was highest in more compliant gels. Simultaneous VEGF and PGE2 secretion was greatest using hydrogels with intermediate mechanical properties, as small increases in stiffness increased VEGF secretion while maintaining PGE2 secretion by entrapped spheroids. The fibrin gel formulation predicted to simultaneously increase VEGF and PGE2 secretion stimulated endothelial cell proliferation, enhanced macrophage polarization, and promoted angiogenesis when used to treat a wounded three dimensional human skin equivalent. These data demonstrate that a statistical approach is an effective strategy to formulate fibrin gel formulations that enhance the wound healing potential of human MSCs. STATEMENT OF SIGNIFICANCE: Mesenchymal stem cells (MSCs) are under investigation for wound healing applications due to their secretion of bioactive factors that enhance granulation tissue formation, blood vessel ingrowth, and reduce inflammation. However, the effectiveness of cell-based therapies is reduced due to poor engraftment and high rates of cell death when transplanted into harsh environments characteristic of large wounds. Compared to dissociated cells, MSCs exhibit increased overall function when aggregated into three-dimensional spheroids, and transplantation of cells using biomaterials is one strategy for guiding cell function in the defect site. The present study demonstrates that the biophysical properties of fibrin hydrogels, designed for use as a cell carrier, can be engineered to dictate the secretion of bioactive factors by entrapped MSC spheroids. This strategy enables MSCs to contribute to wound healing by synergistically promoting neovascularization and modulating the inflammatory milieu. PMID- 28987784 TI - Peritoneal pre-conditioning reduces macrophage marker expression in collagen containing engineered vascular grafts. AB - : Engineered vascular grafts have shown promise as arteriovenous shunts, but they have not yet progressed to clinical trials for coronary arteries <4 mm in diameter such as the coronary arteries. Control over initial biomaterial properties and remodeling are necessary to generate viable grafts. In this study, we blended collagen with a synthetic material, poly(epsilon-caprolactone), to modulate the post-grafting inflammatory response while avoiding aneurysmal-like dilation and failure that can occur with pure collagen grafts. We also used pre implantation in an "in vivo bioreactor" to recruit autologous cells and improve patency after grafting. Electrospun conduits were pre-implanted within rat peritoneal cavities and then grafted autologously into abdominal aortae. Conduit collagen percentages and pre-implantation were tested for their impact on graft remodeling and patency. Burst pressures >2000 mmHg, reproducible expansion with systole/diastole, and maintenance of mechanical integrity were observed. More importantly, peritoneal pre-implantation reduced overall lipid oxidation, intimal layer thickness, and expression of an M1 macrophage marker. The condition with the most collagen, 25%, exhibited the lowest expression of macrophage markers but also resulted in a thicker intimal layer. Overall, the 10% collagen/PCL with peritoneal pre-implantation condition appeared to exhibit the best combination of responses, and may result in improved clinical graft viability. STATEMENT OF SIGNIFICANCE: This manuscript describes a rodent study to systematically determine the benefits of both pre-implantation in the peritoneal cavity and specific ratios of collagen on engineered vascular graft viability. We show that pre-implantation had a significant benefit, including decreasing the expression of macrophage markers and reducing lipid oxidation after grafting. This study is the first time that the benefits of peritoneal pre-implantation have been compared to an "off the shelf," directly grafted control condition. We also demonstrated the importance of specific collagen ratio on the response after grafting. Overall, we feel that this article will be of interest to the field and it has the potential to address a significant clinical need: a graft for coronary arteries <4 mm in diameter. PMID- 28987785 TI - Water effects on the deformation and fracture behaviors of the multi-scaled cellular fibrous bamboo. AB - : Natural bamboo with different water weight contents (0%, 6% and 22%) had distinguishingly different mechanical properties, where samples with water contents of 22% had tensile strength and elongations increased by ~30% and ~200% than the dry (0%), respectively. The deformation and fracture process was synchronously recorded and analyzed with the aid of the acoustic emission (AE), during which there were three kinds of real time fracture behaviors recognized: matrix (multi-walled parenchyma cells) failure, interfacial (fiber/fiber or fiber/parenchyma cell walls) dissociations and fiber breakage. More interfacial dissociations and higher fracture energy were detected as more water was added, since water molecules can make great differences on the bamboo's inner micro structures and the mechanical properties. During the fracture process of the wet bamboo detected by AE, matrix failure and interfacial dissociations contributed most of the elongation, and the strength were mainly depended on the fiber breakage and interfacial dissociations. The discovered structural toughening mechanisms within the multi-scaled structures were microfiber bridging, multi walled fiber pull-out, micro warts buckling and crack deflection. The micro structural toughening effects were strengthened by the cellulose-hemicellulose lignin complexes and a certain content of water molecules within the multi-scaled fibrous cellular structures, which are collaboratively working and ensuring the high mechanical performance of the natural bamboo. STATEMENT OF SIGNIFICANCE: The mechanical behaviors during the whole fracture process of bamboo were investigated by acoustic emission (AE). During the fracture process there were three kinds of fracture behaviors recognized by AE: matrix (parenchyma cells) failure, interfacial (fiber/fiber or fiber/parenchyma cell walls) dissociations and fiber breakage. The mechanical performance was greatly influenced by water contents (0%, 6% and 22%). Wet bamboos had higher fracture energy than the dry ones. There was more interfacial dissociation behaviors detected as more water was absorbed within the multi-scaled structures. The micro structural toughening mechanisms were strengthened by the macromolecular complexes and water molecules, which are working together and ensuring the excellent mechanical properties of the natural bamboo. PMID- 28987786 TI - A simple model of the inner-hair-cell ribbon synapse accounts for mammalian auditory-nerve-fiber spontaneous spike times. AB - The initial neural encoding of acoustic information occurs by means of spikes in primary auditory afferents. Each mammalian primary auditory afferent (type-I auditory-nerve fiber; ANF) is associated with only one ribbon synapse in one receptor cell (inner hair cell; IHC). The properties of ANF spike trains therefore provide an indirect view of the operation of individual IHC synapses. We showed previously that a point process model of presynaptic vesicle pool depletion and deterministic exponential replenishment, combined with short postsynaptic neural refractoriness, accounts for the interspike interval (ISI) distributions, serial ISI correlations, and spike-count statistics of a population of cat-ANF spontaneous spike trains. Here, we demonstrate that this previous synapse model produces unrealistic properties when spike rates are high and show that this problem can be resolved if the replenishment of each release site is stochastic and independent. We assume that the depletion probability varies between synapses to produce differences in spontaneous rate and that the other model parameters are constant across synapses. We find that this model fits best with only four release sites per IHC synapse, a mean replenishment time of 17 ms, and absolute and mean relative refractory periods of 0.6 ms each. This model accounts for ANF spontaneous spike timing better than two influential, comprehensive models of the auditory periphery. It also reproduces ISI distributions from spontaneous and steady-state driven activity from other studies and other mammalian species. Adding fractal noise to the rate of depletion of each release site can yield long-range correlations as typically observed in long spike trains. We also examine two model variants having more complex vesicle cycles, but neither variant yields a markedly improved fit or a different estimate of the number of release sites. In addition, we examine a model variant having both short and long relative refractory components and find that it cannot account for all aspects of the data. These model results will be beneficial for understanding ribbon synapses and ANF responses to acoustic stimulation. PMID- 28987787 TI - Tonotopic organisation of the auditory cortex in sloping sensorineural hearing loss. AB - Although the tonotopic organisation of the human primary auditory cortex (PAC) has already been studied, the question how its responses are affected in sensorineural hearing loss remains open. Twenty six patients (aged 38.1 +/- 9.1 years; 12 men) with symmetrical sloping sensorineural hearing loss (SNHL) and 32 age- and gender-matched controls (NH) participated in an fMRI study using a sparse protocol. The stimuli were binaural 8s complex tones with central frequencies of 400 HzCF, 800 HzCF, 1600 HzCF, 3200 HzCF, or 6400 HzCF, presented at 80 dB(C). In NH responses to all frequency ranges were found in bilateral auditory cortices. The outcomes of a winnermap approach, showing a relative arrangement of active frequency-specific areas, was in line with the existing literature and revealed a V-shape high-frequency gradient surrounding areas that responded to low frequencies in the auditory cortex. In SNHL frequency-specific auditory cortex responses were observed only for sounds from 400 HzCF to 1600 HzCF, due to the severe or profound hearing loss in higher frequency ranges. Using a stringent statistical threshold (p < 0.05; FWE) significant differences between NH and SNHL were only revealed for mid and high-frequency sounds. At a more lenient statistical threshold (p < 0.001, FDRc), however, the size of activation induced by 400 HzCF in PAC was found statistically larger in patients with a prelingual, as compared to a postlingual onset of hearing loss. In addition, this low-frequency range was more extensively represented in the auditory cortex when outcomes obtained in all patients were contrasted with those revealed in normal hearing individuals (although statistically significant only for the secondary auditory cortex). The outcomes of the study suggest preserved patterns of large-scale tonotopic organisation in SNHL which can be further refined following auditory experience, especially when the hearing loss occurs prelingually. SNHL can induce both enlargement and reduction of the extent of responses in the topically organized auditory cortex. PMID- 28987788 TI - Biomechanics and developmental potential of oocytes and embryos. AB - The high incidence of multiple embryo transfers is evidence of the need for better methods of embryo selection. Additionally, methods to determine the reproductive competence of unfertilized oocytes are critically needed to inform the growing population of patients undergoing fertility preservation. The ideal method of oocyte and embryo selection would be noninvasive, inexpensive, and able to be incorporated into embryology workflow with minimal disruption. Methods to assess the biomechanical properties of cells offer many of these traits, and there is a growing body of evidence in multiple cell types demonstrating the biomechanical properties of cells are reflective of a cell's intrinsic health. The associations with these properties are not mere coincidence, as many of the biomechanical properties are critical to cellular function. The biomechanical properties of oocytes and embryos undergo a dynamic, characteristic transformation from oocyte maturation through blastocyst formation, lending itself to biomechanical assessment. Many of the assessments made by embryologists, from ease of microinjection during intracytoplasmic sperm injection to degree of blastocyst expansion, are direct proxies for cellular biomechanics. Newer, objective and quantitative methods of biomechanical assessment are being applied to oocyte and embryo selection, with early use supporting their application in assisted reproduction. PMID- 28987789 TI - Female age, serum antimullerian hormone level, and number of oocytes affect the rate and number of euploid blastocysts in in vitro fertilization/intracytoplasmic sperm injection cycles. AB - OBJECTIVE: To study the relative role of female age and ovarian reserve, measured through serum antimullerian hormone (AMH) in determining the rate and number of euploid blastocysts in in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles. DESIGN: Retrospective analysis of cycles performed in 2014-2015. SETTING: Tertiary referral IVF center. PATIENT(S): A total of 578 infertile couples undergoing IVF/ICSI and preimplantation genetic screening (PGS) analysis. INTERVENTIONS(S): All embryos were cultured and biopsied at the blastocyst stage. The method involved whole-genome amplification followed by array comparative genome hybridization. Serum AMH was measured by means of the modified Beckman Coulter AMH Gen II assay. MAIN OUTCOME MEASURES: The rate and number of euploid blastocysts and their correlation with ovarian reserve and response to stimulation. RESULT(S): The mean (+/-SD) age of patients was 37.6 +/- 4.1 years, and the mean number of blastocysts per patient was 3.1 +/- 2. The total number of blastocysts available to the analysis was 1,814, and 36% of them were euploid after PGS. Age and serum AMH were significantly and independently related to the rate of euploid blastocysts available for patients. As an effect of the cohort size, the number of mature oocytes positively affected the total number of euploid blastocysts per patient. CONCLUSION(S): A strong positive age independent relationship between AMH level and the rate of euploid blastocysts was found. This confirms that the measurement of ovarian reserve by means of AMH has high relevance when counseling infertile patients. PMID- 28987790 TI - Simultaneous determination of fluoxetine and norfluoxetine in dried blood spots using high-performance liquid chromatography-tandem mass spectrometry. AB - BACKGROUND: Therapeutic drug monitoring (TDM) of the widely prescribed antidepressant fluoxetine (FLU) is recommended in certain situations, such as occurrence of toxicity, inadequate response or suspect of poor adherence. Dried blood spot (DBS) sampling is an increasingly studied alternative for TDM, particularly for outpatients, due to its ease of collection and inherent stability. OBJECTIVES: The aim of this study was to develop and validate an LC MS/MS assay for the simultaneous quantification of FLU and norfluoxetine (NFLU) in DBS. DESIGN AND METHODS: The assay is based on a liquid extraction of single DBS with 8mm of diameter, using FLU-D6 as the internal standard, followed by reversed phase separation in an Accucore(r) C18 column (100*2.1mm, 2.6MUm). Mobile phase was composed of water and acetonitrile (gradient from 80:20 to 50:50, v/v), both containing formic acid 0.1%. The assay was validated and applied to 30 patients under FLU pharmacotherapy. RESULTS: The assay was linear in the range 10-750ngmL-1. Precision assays presented CV% of 3.13-9.61 and 3.54 7.99 for FLU and NFLU, respectively, and accuracy in the range of 97.98-110.44% and 100.25-105.8%. FLU and NFLU were stable at 25 and 45 degrees C for 7days. The assay was evaluated in 30 patients under FLU treatment. Concentrations of both compounds were higher in DBS than in plasma, and the use of the multiplying factors 0.71 and 0.68 for FLU and NFLU, respectively, allowed acceptable estimation of plasma concentrations, with median prediction bias of -0.55 to 0.55% and mean differences of 0.4 to 2.2ngmL-1. CONCLUSIONS: The presented data support the clinical use of DBS for therapeutic drug monitoring of FLU. PMID- 28987791 TI - Serum interleukin measurement may help identify thyroid cancer patients with active disease. AB - BACKGROUND: Investigate the clinical utility of serum interleukin dosages of IL 2, IL-2R, IL-4, IL-6, IL-6R, IL-8, IL-10 and IL-12 in the diagnosis and characterization of patients with DTC. In particular, verify ILs utility in the identification of individuals who are evolving disease-free or with the active disease. METHODS: We evaluated 200 patients with malignant nodules (100 patients disease-free and 100 patients with recurrence/active disease); 60 benign nodules and 100 healthy controls, serum levels were assessed by ELISA. RESULTS: All ILs, but not IL-4, differentiated these three groups. We observed that IL-2, 2R and 10 serum concentrations were associated with thyroglobulin levels. Serum IL-2 was able to differentiate patients with active disease from the disease-free with a sensitivity of 98%, specificity of 58%, positive predictive value (PPV) of 70% and negative predictive value (NPV) of 97% (p=0.0007). IL-6R levels differentiated patients with active disease from the disease-free patients with 56% sensitivity, 63% specificity, PPV of 60% and NPV of 59% (p<0.0001). IL-8 values also distinguished patients with active disease from the disease-free ones with sensitivity of 50%, specificity of 76%, PPV of 68% and NPV of 60% (p=0.0025); using IL-12, we obtained a sensitivity value of 73%, specificity of 66%, PPV of 68% and NPV of 71% (p<0.0001). Furthermore, interleukin levels showed association with some tumor characteristics of aggressiveness. CONCLUSION: We suggest that the serum concentration of ILs may assist in the diagnosis and characterization of tumor malignancy helping identify patients with active disease who deserve closer medical attention. PMID- 28987792 TI - Cordycepin induces apoptotic cell death of human brain cancer through the modulation of autophagy. AB - Brain cancer, in particular neuroblastoma and glioblastoma, is a global challenge to human health. Cordycepin, extracted from Cordyceps ssp., has been revealed as a strong anticancer agent through several ways; however, the mechanism, by which cordycepin counteracts brain cancers, is still poorly understood. In this study, the underlying mechanisms of cordycepin against human brain cancer cells were explored. SH-SY5Y and U251 cells were being a model to represent human neuroblastoma and glioblastoma, respectively. Here, it was found that cordycepin inhibited cell growth, and induced apoptosis in a dose-dependent manner in both SH-SY5Y and U-251 cell lines. The expression of pro-apoptotic genes, including P53, BAX, Caspase-3, and Caspase-9, were upregulated, whereas the expression of anti-apoptotic gene, BCL-2, was suppressed. Besides, cordycepin induced the generation of reactive oxygen species (ROS) along with the suppression of antioxidant genes, including GPX, SOD, and Catalase. Importantly, cordycepin was shown to involve in the activation of autophagy, which was evidenced by the increment of LC3I/II. The combination of cordycepin with chloroquine, an autophagy inhibitor, further inhibited the growth, and enhanced the death of brain cancer cells. Altogether, this finding suggested that cordycepin induced apoptosis of human brain cancer cells through mitochondrial-mediated intrinsic pathway and the modulation of autophagy. Therefore, cordycepin could be a promising candidate for the development of anticancer drugs targeting human brain cancers. PMID- 28987793 TI - Silver nanoparticles induce lysosomal-autophagic defects and decreased expression of transcription factor EB in A549 human lung adenocarcinoma cells. AB - Although silver nanoparticles (AgNPs) are widely used in consumer and medical products, the mechanism by which AgNPs cause pulmonary damage is unclear. AgNPs are incorporated into cells and processed via the autophagy pathway. We examined the effects of AgNP exposure on autophagic flux and expression of transcription factor EB (TFEB) in A549 lung adenocarcinoma cells. In cells exposed to citrate coated 60-nm AgNPs, confocal laser microscopic examination showed a decrease in the LysoTracker fluorescence signal and an increase in that of Cyto-ID, indicating lysosomal pH alkalization and autophagosome formation, respectively. The proteins p62 and microtubule-associated protein light chain 3B-II (LC3B-II) are both degraded by autophagy, and their levels increased depending on AgNP dose. Furthermore, AgNP-induced increase in LC3B-II was not enhanced by treatment with the autophagic inhibitor bafilomycin A1. TFEB mRNA levels, and protein levels in cytosolic and nuclear fractions, were suppressed by exposure to AgNPs, suggesting transcriptional inhibition of TFEB expression. Overexpression of TFEB did not suppress AgNP-induced LC3B-II accumulation and cellular damage, indicating that impairment of autophagic flux and cellular damage by AgNPs might not be primarily caused by reduced TFEB expression. The present study suggests that AgNP-induced lysosomal dysfunction plays a principal role in the autophagic flux defect. PMID- 28987794 TI - The excitotoxity of NMDA receptor NR2D subtype mediates human fetal lung fibroblasts proliferation and collagen production. AB - Studies have suggested that endogenous glutamate and N-methyl-d-aspartate (NMDA) receptor have an excitotoxity role during acute lung injury. Fibroblasts play a critical role in lung development and chronic lung disease after acute lung injury. This study aims to explore the immediate role of NMDAR activation in human lung fibroblasts. The expression of NMDAR 1 subtype (NR1) and four individual NMDAR 2 (NR2) subtypes (NR 2 A to D) was measured in human fetal lung fibroblasts (HFL-1 and MRC-5). Five NMDARs expression were all detectable in two cell lines. Although the expressions of NMDARs were different between MRC-5 and HFL-1, 1mM NMDA elicited the same trend in the downregulation of NR2A expression, the upregulation of NR2D, and the increase of cells proliferation and collagen production. Glutamate stimulation after 24-h of NMDA exposure resulted in weaker and more delayed but more prolonged iCa2+ elevation in HFL-1 than no NMDA exposed cells. NMDA increased the level of pERK1/2, cells proliferation and collagen production, whereas nonspecific NMDAR antagonist MK-801, NR2D-preferring receptor antagonist UBP141 and ERK1/2 phosphorylation inhibitor U0126 suppressed it, respectively. In conclusion, we found that NMDAR activation, NR2D in particular, is involved in human fetal lung fibroblast proliferation and collagen production through a potential ERK1/2-mediated mechanism. PMID- 28987795 TI - Morphological evaluation of Day 8 embryos developed during induced aluteal cycles in the mare. AB - A novel in vivo model utilizing serial administrations of PGF2alpha to induce aluteal cycles in the mare was used to evaluate the effects of progesterone deprivation on the morphology of in vivo preimplantation embryos. We hypothesized that equine embryos produced during induced aluteal cycles (AL) would be developmentally affected, characterized by earlier embryo stage at collection, smaller embryo diameter, and lower quality grade, compared with those collected on the same day post-ovulation from control cycles during diestrus (high progesterone; > 4 ng/mL). Seven cyclic mares with a median age of 6.5 years (range 3-16) were utilized in a crossover design. Mares in estrus were artificially inseminated to a fertile stallion and randomly assigned to control or AL groups. Mares received either saline solution (control mares) or PGF2alpha (AL mares), twice daily on days 0, 1, and 2 and once daily on days 3 and 4. Serial blood samples were collected daily during estrus and until the day of embryo collection 8 days after ovulation. Mares were monitored until they returned to estrus, and artificially inseminated. Mares were switched to the opposite treatment group only after a successful embryo collection occurred during the previous cycle. Only cycles that produced embryos were used for analyses. No significant rise in progesterone was observed in the AL group with mean concentrations of plasma progesterone remaining <1.0 ng/mL from ovulation until embryo collection on Day 8. This is in sharp contrast to the control (luteal) cycle where a post-ovulatory rise in plasma progesterone was observed. The mean daily concentrations of plasma progesterone were significantly higher in control vs. AL group beginning at Day 3 and remained so until Day 8. The mean (+/ SEM) embryo diameter of AL embryos was 171 +/- 5 MUm compared to 756 +/- 99 MUm for control embryos. The majority of the Day 8 AL embryos were classified as morulas (3/9) or early blastocysts (5/9) with only 2 embryos of quality grade 1 compared to the Day 8 control embryos that were mostly expanded blastocysts (6/7) with 5 of 6 being of quality grade 1. This study shows that serial administrations of PGF2alpha were able to prevent significant rises in plasma progesterone, thus inducing aluteal cycles characterized by a progesterone deprived environment for developing embryos. Embryos collected from induced aluteal cycles were adversely affected as demonstrated by a lower quality grade, smaller diameter and earlier embryo stage at collection when compared to control embryos. PMID- 28987796 TI - Physico-chemical characterization and pharmacological activities of polysaccharides from Opuntia microdasys var. rufida cladodes. AB - The aim of this study is to isolate pectin from peel (WNPE) and pulp (WNPU) of Opuntia microdasys var. rufida's (OMR) cladodes and to characterize these polysaccharides by size exclusion (SEC/MALS/VD/DRI), gas chromatography coupled to mass spectrometer (GC-MS), nuclear magnetic resonance (1H NMR), and Fourier transform infrared spectroscopy (FTIR) analysis. The polysaccharides were extracted in neutral aqueous media followed by ethanol precipitation and dialysis. Both WNPE and WNPU are mainly composed of uronic acids and some neutral sugars such as arabinose, galactose, rhamnose and mannose. Their molecular weight range from 2,180,000 and 4,920,000g/mol. The in-vivo pharmacological activities (anti-inflammatory, analgesic and gastroprotective activities) have been performed. The extracted pectin (50-100mg/kg, i.p. (intraperitoneal)) inhibited, in a dose-related manner, both carrageenan-induced paw edema in rats and Xylene induced ear edema in mice. A dose-dependent action was obtained against chemical (writhing test) and thermic (hot plate test) stimuli, respectively, with doses of 50 and 100mg/kg. Moreover, a considerable gastroprotective effect was observed with these two biopolymers, the gastric ulcer was attenuated until 67.67% for WNPE and 81.93% for WNPU, at the dose of 100mg/kg. PMID- 28987797 TI - Investigating the site selective binding of busulfan to human serum albumin: Biophysical and molecular docking approaches. AB - We have studied the binding of busulfan (BN) to human serum albumin (HSA) at physiological pH 7.4 by using fluorescence, UV-vis and circular dichroism (CD) spectroscopic tools, as well as dynamic light scattering (DLS) measurements and molecular simulation approaches. HSA fluorescence quenching experiments showed that BN reduces the HSA native fluorescence intensity through the static mechanism. In addition, a single binding site on the HSA is occupied by BN with a binding constant at 298K of 1.84*103M-1. The enthalpy change (DeltaH) and entropy change (DeltaS) of BN-HSA interaction were calculated as -1.40kcalmol-1 and +10.14calmol-1K-1 respectively, which suggest the possible interaction mode as hydrophobic and hydrogen bonding. Moreover, the secondary structure alteration of HSA following its complexation with BN was studied and showed that alpha-helical content of HSA gets increased on interacting with BN. Ligand binding site to HSA was further investigated by site-specific markers in fluorescence measurements as well molecular modeling approach which indicated that BN bind to the nearby sudlow site II of HSA through hydrophobic as well as hydrogen bonding interaction. The present study will be helpful for understanding the binding mechanism of BN to human serum albumin. PMID- 28987798 TI - Exploration of G-quadruplex function in c-Myb gene and its transcriptional regulation by topotecan. AB - Our bioinformatics research shows that there are four G-rich sequences (S1-S4) in the upstream region of the transcription start site of c-Myb gene, and we have proved that these sequences have the ability to form G-quadruplex structures. This work mainly focuses on G-quadruplex function, recognition and transcription regulation in c-Myb gene, revealing a novel regulatory element in c-Myb proximal promoter region, and its transcription regulation by G-quadruplex binder. The research has identified that the enhancer effect in c-Myb transcription was primarily affected by the G-quadruplex formed by S1 sequence, and the up regulation effect may due to the removal of repressive progress of MZF-1 by stabilizing G-quadruplex. Attentions were being paid to the development of G quadruplex binders for selective recognition, and topotecan was found to have high binding affinity in vitro and could effectively affect the c-Myb transcription activities in cells. The regulation of G-quadruplex with binders in transcriptional, translational levels by Q-RT-PCR and western blot was in expectation of providing a strategy for gene expression modulation. In conclusion, our study revealed a G-quadruplex structure in c-Myb proximal promoter region, which was of great importance in the regulation of c-Myb function. PMID- 28987799 TI - Xyloglucan from Hymenaea courbaril var. courbaril seeds as encapsulating agent of l-ascorbic acid. AB - This study evaluated the l-ascorbic acid (AA) encapsulation in microparticles of xyloglucan (XAA) extracted from Hymenaea courbaril seeds by spray drying (SD) and its application in tilapia fish burgers. The encapsulation efficiency was 96.34+/ 1.6% and the retention of the antioxidant activity was of 89.48+/-0.88% after 60days at 25 degrees C. SEM images showed microspheres with diameters ranging from 4.4 to 34.0MUm. FTIR spectrum confirmed the presence of AA in xyloglucan microparticles, which was corroborated by DSC and TGA. The release of ascorbic acid was found to be pH-dependent. The application of XAA in tilapia fish burger did not change the pH after heating and the ascorbic acid retention was greater compared to its free form. The results indicate that xyloglucan can be used to encapsulate AA by SD and suggest that XAA was able to reduce undesirable organoleptic changes in fish burgers. PMID- 28987800 TI - Characterization of fish myofibrillar protein film incorporated with catechin Kradon extract. AB - This study investigates the properties of films made from fish myofibrillar protein (FMP) incorporated with combinations of catechin-Kradon extract (C/K) (20%, w/w) at different ratios. The experimental films were compared to a polyvinyl chloride (PVC). The thickness and the transparency of the films were in the range of 0.014-0.015mm and 3.65-3.77, respectively. Significant decreases were observed in elongation at break (35-122%), water vapor permeability (0.54 1.26*10-10gm-1s-1Pa-1) properties, and a gradual decrease in L* value was pronounced when the proportions of catechins were increased (P<0.05). FMP films incorporated with C/K demonstrated to have very good barrier properties to UV light and also enhanced the thermal stability of the developed FMP films. All film samples had a smooth surface; however coarser surfaces were observed when the amounts of catechins were increased. Furthermore, the developed FMP films showed high antioxidant capability. However, no significant antimicrobial activity was observed in this film. It is determined that FMP films enriched with C/K can be used for food packaging, with particular potential for active packaging. However, as compared with the PVC, the FMP films need further development, especially in terms of their mechanical and water barrier properties. PMID- 28987801 TI - Production enhancement and characterization of the polyhydroxyalkanoate produced by Natrinema ajinwuensis (as synonym) = Natrinema altunense strain RM-G10. AB - Application of halophiles can decrease the cost of polyhydroxyalkanoate (PHA) production or bioplastic which are an alternative to the petroleum-derived plastic. Extremely halophilic archaeon, Natrinema ajinwuensis RM-G10 accumulated 61.02+/-0.68% PHA of its cell dry mass at 72h in repeated batch cultures yielding 0.210+/-0.001gL-1h-1 volumetric productivity after selection of the best cultivation conditions. Transmission electron microscopy showed the presence of PHA granules inside the archaeal cells. Characterization by gas chromatographic analysis, gas chromatographic- mass spectrophotometric analysis, thermogravimetric analysis, differential scanning calorimetric analysis, X-ray diffraction analysis, Fourier transform infra red spectroscopy and nuclear magnetic resonance spectroscopy revealed the polymer to be poly(3-hydroxybutyrate co-3-hydroxyvalerate) with 13.93mol% 3-hydroxyvalerate content and having 35.45% crystallinity, -12.3 degrees C glass transition temperature, 143 degrees C and 157.5 degrees C melting temperatures and 284 degrees C degradation temperature. This is the first report on production enhancement (on a small scale) and characterization of the polyhydroxyalkanoate produced by Natrinema ajinwuensis (as synonym) = Natrinema altunense strain RM-G10 and the Natrinema genus in general. PMID- 28987802 TI - American lobster Cathepsin D, an aspartic peptidase resistant to proteolysis and active in organic solvents, non-ionic detergents and salts. AB - Suitable peptidases for biotechnological applications are those active at low temperature, in organic solvents, detergents or proteolytic additives. American lobster cathepsin D1 (CD1) is an enzyme highly efficient at 5-50 degrees C and at pH 2.5-5.5. We assessed the effect of common industrial additives on CD1 activity. CD1 was isolated from lobster gastric fluid by chromatography. The proteolytic activity was measured using a fluorogenic specific substrate and the conformation by intrinsic fluorescence. Non-ionic detergents Tween-20 and Triton X-100 stabilize the peptidase activity. Ethanol, methanol and isopropanol [5-15% (v/v)] increased the enzyme activity up to 80%. The enzyme is active until 2.5M urea and is resistant to proteolysis by papain and renin. In this work, a crustacean peptidase that remains active when exposed to different chemical and proteolytic additives is reported, evincing that crustaceans are a good model for discovery of novel stable peptidases for future pharmaceutical, cosmetic and alimentary applications. PMID- 28987803 TI - Long-acting beta2-adrenoreceptor agonists suppress type 1 interferon expression in human plasmacytoid dendritic cells via epigenetic regulation. AB - The combination of inhaled long-acting beta2-adrenoreceptor (LABA) and inhaled glucocorticoid (ICS) is a major therapy for asthma. However, the increased risk of infection is still a concern. Plasmacytoid dendritic cells (pDCs) are the predominant cells producing type 1 interferon (IFN) against infection. The effect of LABA/ICS on type 1 IFN expression in human pDCs is unknown. Circulating pDCs were isolated from healthy human subjects and were pretreated with glucocorticoid (GCS), LABA or a cAMP analog, and were stimulated with Toll-like receptor (TLR) agonist CpG (TLR9) or imiquimod (TLR7) in the presence of IL-3. The expression of type 1 IFN (IFN-alpha/beta) were measured by ELISA. The mechanisms were investigated using receptor antagonists, pathway inhibitors, Western blotting and chromatin immunoprecipitation. GCS suppressed TLR-induced IFN-alpha expression, and LABA enhanced the suppressive effect. LABA alone also suppressed TLR-induced IFN-alpha/beta expression, and the effect was reversed by the beta2 adrenoreceptor antagonist ICI118551. Dibutyryl-cAMP, a cAMP analog, conferred a similar suppressive effect, and the effect was abrogated by the exchange protein directly activated by cAMP (Epac) inhibitor HJC0197 or intracellular free Ca2+ chelator BAPTA-AM. Formoterol suppressed TLR-induced phosphorylation of mitogen activated protein kinase (MAPK)-p38/ERK. Formoterol suppressed interferon regulatory factor (IRF)-3/IRF-7 expression. Formoterol suppressed CpG-induced translocation of H3K4 specific methyltransferase WDR5 and suppressed H3K4 trimethylation in the IFNA and IFNB gene promoter region. LABA suppressed TLR7/9 induced type 1 IFNs production, at least partly, via the beta2-adrenoreceptor cAMP-Epac-Ca2+, IRF-3/IRF-7, the MAPK-p38/ERK pathway, and epigenetic regulation by suppressing histone H3K4 trimethylation through inhibiting the translocation of WDR5 from cytoplasm to nucleus. LABA may interfere with anti-viral immunity. PMID- 28987804 TI - Pharmacodynamics, pharmacokinetics and safety of revefenacin (TD-4208), a long acting muscarinic antagonist, in patients with chronic obstructive pulmonary disease (COPD): Results of two randomized, double-blind, phase 2 studies. AB - BACKGROUND: Revefenacin (TD-4208) is a potent, lung-selective, long-acting muscarinic antagonist currently in development as a once-daily nebulized therapy for chronic obstructive pulmonary disease (COPD). We evaluated the pharmacodynamics (bronchodilator activity), pharmacokinetics (PK) and safety of single- and multiple-dose administrations of revefenacin in two clinical trials (Study 0059 and Study 0091) in patients with moderate to severe COPD. METHODS: In Study 0059, 32 patients were randomized to receive a single dose of revefenacin (350 or 700 MUg), active control ipratropium (500 MUg) or placebo inhalation solution administered via standard jet nebulizer in a double-blind, crossover fashion. In Study 0091, 59 patients were randomized to receive once-daily inhalations of revefenacin (22, 44, 88, 175, 350 or 700 MUg) or placebo for 7 days in a double-blind, incomplete block, five-way crossover design. The primary efficacy endpoint was change from baseline in peak (0-6 h) forced expiratory volume in 1 s (FEV1) in Study 0059, and trough FEV1 after the final dose (Day 7) in Study 0091. In both studies, secondary endpoints included area under the FEV1 time curve (FEV1 AUC) values from time 12-24 h post dose and FEV1 AUC values from time zero to 24 h post dose. RESULTS: Revefenacin demonstrated a rapid onset and sustained duration of bronchodilator action in both studies. In Study 0059, mean peak FEV1 was significantly higher (p < 0.001) for revefenacin and ipratropium compared to placebo, with differences of 176.8 mL for 350 MUg revefenacin, 162.2 mL for 700 MUg revefenacin and 190.6 mL for ipratropium. In Study 0091, mean trough FEV1 on Day 7 was significantly higher (p < 0.006) for all revefenacin doses compared to placebo, with differences ranging from 53.5 mL (22 MUg dose) to 114.2 mL (175 MUg dose). The results for the other spirometry endpoints were consistent with the primary endpoint for each study, demonstrating that the bronchodilator effect of revefenacin lasted more than 24 h following nebulized administration. Revefenacin was rapidly absorbed and extensively metabolized, followed by a slow apparent terminal elimination and minimal accumulation with repeated dosing. In both studies, adverse events were generally mild and occurred with similar frequencies in all groups, with no indication of significant systemic anti-muscarinic activity at any dose. CONCLUSIONS: Following single or multiple nebulized-dose administration in patients with COPD, revefenacin demonstrates a rapid onset and sustained duration of bronchodilator effect over 24 h following once-daily administration, with a PK profile that is commensurate with low systemic exposure. PMID- 28987805 TI - Emergence of carbapenem resistant Escherichia coli isolates producing blaNDM and blaOXA-48-like carried on IncA/C and IncL/M plasmids at two Iranian university hospitals. AB - The emergence of carbapenem resistance among Escherichia coli is a serious threat to public health. The objective of this study was to investigate resistance genes and clonality of carbapenem resistant E. coli in Iran. Between February 2015 and July 2016, a total of 32 non-duplicate E. coli isolates that were ertapenem resistant or intermediate (R/I-ETP) were collected from patient clinical or surveillance cultures (rectal swabs) at two university hospitals. Resistance genes were identified by PCR and sequencing. Conjugation experiments, PCR-based replicon typing, PFGE and multilocus sequence typing (MLST) were performed. PCR assays showed, among the 32 isolates, twenty-nine strains produced carbapenemase genes. The predominant carbapenemase was blaOXA-48 (82.8%), followed by blaNDM-1 (31%), blaNDM-7 (6.9%) and blaOXA-181 (3.4%). Seven of the blaNDM positive isolates co-harbored blaOXA-48 carbapenemases. The blaNDM and blaOXA-48 were found in IncA/C and IncL/M conjugative plasmids, respectively. The blaCTX-M-15, qnrA and intI1 genes were also present in most isolates. The PFGE revealed genetic diversity among the 28 E. coli isolates, which belonged to six minor PFGE clusters and 14 isolates were singletons. The 26 isolates were distributed into 18 STs, of which two were dominant (ST648 and ST167). We identified one blaNDM-1 positive ST131 E. coli isolates that harbor the blaCTX-M-15 and blaTEM genes. Horizontal transfer of IncA/C and IncL/M plasmids has likely facilitated the spread of the blaOXA-48 and blaNDM genes among E. coli. Their clonal diversity and the presence of faecal carriers in isolates suggest an endemic spread of OXA 48 and NDM. Therefore, it emphasizes the critical importance of monitoring and controlling the spread of carbapenem resistant E. coli. PMID- 28987807 TI - Canine susceptibility to visceral leishmaniasis: A systematic review upon genetic aspects, considering breed factors and immunological concepts. AB - Dogs have different susceptibility degrees to leishmaniasis; however, genetic research on this theme is scarce, manly on visceral form. The aims of this systematic review were to describe and discuss the existing scientific findings on genetic susceptibility to canine leishmaniasis, as well as to show the gaps of the existing knowledge. Twelve articles were selected, including breed immunological studies, genome wide associations or other gene polymorphism or gene sequencing studies, and transcription approaches. As main results of literature, there was a suggestion of genetic clinical resistance background for Ibizan Hound dogs, and alleles associated with protection or susceptibility to visceral leishmaniasis in Boxer dogs. Genetic markers can explain phenotypic variance in both pro- and anti-inflammatory cytokines and in cellular immune responses, including antigen presentation. Many gene segments are involved in canine visceral leishmaniasis phenotype, with Natural Resistance Associated Macrophage Protein 1 (NRAMP1) as the most studied. This was related to both protection and susceptibility. In comparison with murine and human genetic approaches, lack of knowledge in dogs is notorious, with many possibilities for new studies, revealing a wide field to be assessed on canine leishmaniasis susceptibility research. PMID- 28987806 TI - Full-length genomic sequences of new subtype 1g hepatitis E virus strains obtained from four patients with imported or autochthonous acute hepatitis E in Japan. AB - Hepatitis E virus (HEV) causes acute or chronic hepatitis in humans worldwide and can be transmitted via the fecal-oral route. Four HEV strains (HE-JA14-2173, HE JA15-1335, HE-JA15-1920 and HE-JA16-0610) obtained from patients with imported (from Pakistan or India) or autochthonous acute hepatitis E in Japan were most closely related to the Nepalese and Mongolian genotype 1 HEV strains of unassigned subtype within the partial ORF2 sequence. To investigate whether a putative novel subtype (1g) of genotype 1 can be assigned, full-length genomic sequences were determined for the four HEV strains. They shared 95.4-99.2% nucleotide identity over the entire genome, and differed by 6.3-11.7% from the reported HEV strains of subtypes 1a-1f and by only 0.6-4.7% from a Mongolian genotype 1 HEV strain (MNE15-072) of unassigned subtype. A phylogenetic analysis showed that the four HEV strains obtained in the present study formed a cluster with MNE15-072, with a bootstrap value of 100%. Although the p-distance between subtypes 1a and 1f was 0.048-0.083, these five strains showed a higher nucleotide p-distance value of 0.068-0.138 with the genotype 1 HEV strains of subtypes 1a 1f. A BLAST search revealed the presence of candidate members of subtype 1g HEV in at least five other countries, including France, Israel, the Netherlands, Portugal, and the UK, sharing identities of 95.4-99.6% with the HE-JA16-0610 strain within the common sequence of 294-867 nucleotides. These results support the assignment of a new subtype 1g within genotype 1 and suggest a global distribution of subtype 1g strains. Subtype 1g strains found in Europe can be imported from Asia. Further studies are needed to confirm the global distribution of HEV subtype 1g. PMID- 28987808 TI - Landscape epidemiology in urban environments: The example of rodent-borne Trypanosoma in Niamey, Niger. AB - Trypanosomes are protozoan parasites found worldwide, infecting humans and animals. In the past decade, the number of reports on atypical human cases due to Trypanosoma lewisi or T. lewisi-like has increased urging to investigate the multiple factors driving the disease dynamics, particularly in cities where rodents and humans co-exist at high densities. In the present survey, we used a species distribution model, Maxent, to assess the spatial pattern of Trypanosoma positive rodents in the city of Niamey. The explanatory variables were landscape metrics describing urban landscape composition and physiognomy computed from 8 land-cover classes. We computed the metrics around each data location using a set of circular buffers of increasing radii (20m, 40m, 60m, 80m and 100m). For each spatial resolution, we determined the optimal combination of feature class and regularization multipliers by fitting Maxent with the full dataset. Since our dataset was small (114 occurrences) we expected an important uncertainty associated to data partitioning into calibration and evaluation datasets. We thus performed 350 independent model runs with a training dataset representing a random subset of 80% of the occurrences and the optimal Maxent parameters. Each model yielded a map of habitat suitability over Niamey, which was transformed into a binary map implementing a threshold maximizing the sensitivity and the specificity. The resulting binary maps were combined to display the proportion of models that indicated a good environmental suitability for Trypanosoma-positive rodents. Maxent performed better with landscape metrics derived from buffers of 80m. Habitat suitability for Trypanosoma-positive rodents exhibited large patches linked to urban features such as patch richness and the proportion of landscape covered by concrete or tarred areas. Such inferences could be helpful in assessing areas at risk, setting of monitoring programs, public and medical staff awareness or even vaccination campaigns. PMID- 28987809 TI - Monitoring inflammatory heterogeneity with multiple biomarkers for multidimensional endotyping of asthma. PMID- 28987810 TI - Chronic rhinosinusitis in Asia. AB - Chronic rhinosinusitis (CRS), although possibly overdiagnosed, is associated with a high burden of disease and is often difficult to treat in those truly affected. Recent research has demonstrated that inflammatory signatures of CRS vary around the world, with less eosinophilic and more neutrophilic inflammation found in Asia compared with Europe and North America. Although in the Western world about 80% of nasal polyps carry a type 2 signature, this might be between 20% and 60% in China and Korea or Thailand, respectively. These differences are associated with a lower asthma comorbidity and risk of disease recurrence after surgery in the Asian population. As a hallmark of severe type 2 inflammation, eosinophils attacking Staphylococcus aureus at the epithelial barrier have been described recently; they also can be found in a subgroup of Asian patients with nasal polyps. Furthermore, the percentage of type 2 signature disease in patients with CRS is dramatically increasing ("eosinophilic shift") in several Asian countries over the last 20 years. Establishing an accurate diagnosis along with considering the current and shifting patterns of inflammation seen in Asia will enable more effective selection of appropriate pharmacotherapy, surgical therapy, and eventually biotherapy. Determining the causes and pathophysiology for this eosinophilic shift will require additional research. PMID- 28987812 TI - IL6 polymorphisms modify the effects of smoking on the risk of adult asthma. PMID- 28987811 TI - The interferon gene signature is increased in patients with early treatment-naive rheumatoid arthritis and predicts a poorer response to initial therapy. PMID- 28987813 TI - On the distribution and inventories of radionuclides in dated sediments around the Swedish coast. AB - The activity concentrations and distribution of 137Cs, 238Pu, 239+240Pu, 241Am, and 210Pb was determined by the analysis of six sediment cores from the Baltic Sea and Kattegat. The chronology of the sediment cores has been used to evaluate the origin and time trend of the radionuclide sources in these sediments. The sediment cores were dated with a 210Pb model and the results were validated with fallout peaks, assumed to originate from the global nuclear weapons testing and the Chernobyl accident. Source identification, using the isotopic and radionuclide activity ratios, showed that the Chernobyl accident is the main source of 137Cs in the Baltic Sea; for 239+240Pu and 241Am the dominant source was shown to be fallout from nuclear weapons tests. For 238Pu and 241Am the Chernobyl accident had a significant impact on the direct fallout into the Baltic Proper, with up to a 65% contribution in the sediment slices dated to 1986. In these sediment slices the maximum activity ratios of 238Pu/239+240Pu and 241Am/239+240Pu were 0.314 +/- 0.008 and 1.29 +/- 0.06, respectively. The ratios clearly deviate from the corresponding ratios for global nuclear weapons fallout (around 0.028 and 0.54, respectively). Calculated inventories were 63-175 Bq.m-2 for 239+240Pu, 2.8-7.8 for 238Pu Bq.m-2 and 0.92-44.4 kBq.m-2 for 137Cs. Different fallout patterns for 137Cs and plutonium isotopes from the Chernobyl accident were confirmed through depth profiles analyses. The maximum inventory of 137Cs was observed in the Bothnian Sea, while Chernobyl-derived plutonium was found to be mostly present in Northern Baltic Proper. The radionuclides distribution in the depth profiles shows how contaminated water affects the sediment as it passes sampling stations according to the current circulation pattern in the Baltic Sea. Additionally, the effect of increased activity concentrations from of river discharges in the most contaminated area in the Bothnian Sea was observed. PMID- 28987814 TI - Mathematical modeling of gonadotropin-releasing hormone signaling. PMID- 28987815 TI - Authors response to communication about mathematical modeling of gonadotropin releasing hormone signaling. PMID- 28987816 TI - Aspirin increases ferroportin 1 expression by inhibiting hepcidin via the JAK/STAT3 pathway in interleukin 6-treated PC-12 cells. AB - To understand the potential mechanisms involved in the beneficial effects of aspirin (ASA) in mood disorders, Alzheimer's (AD) and Parkinson's disease (PD), we investigated the effects of ASA on the expression of iron transport proteins transferrin receptor 1 (TfR1), ferroportin 1 (Fpn1), and iron storage protein ferritin light chain (Ft-L) in interleukin-6 (IL-6)-treated PC-12 cells. We demonstrated that IL-6 alone could induce a severe decline in Fpn1 expression and cell viability, and an increase in Ft-L protein, while ASA could markedly diminish the effects of IL-6 on these parameters. We also found that IL-6 significantly increased hepcidin expression and janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) phosphorylation, while ASA also observably suppressed these IL-6-induced effects. The data imply that ASA increases Fpn1 expression by inhibiting hepcidin expression via the IL 6/JAK/STAT3 pathway and show that the reduced content of Ft-L is due to the increased Fpn1 and subsequent iron release in the cells. The reduction of iron in neuronal cells by the increased expression of Fpn1 might be partly associated with the beneficial effects of ASA on mood disorders, AD and PD. PMID- 28987817 TI - The sodium channel activator Lu AE98134 normalizes the altered firing properties of fast spiking interneurons in Dlx5/6+/- mice. AB - Mental disorders such as schizophrenia are associated with impaired firing properties of fast spiking inhibitory interneurons (FSINs) causing reduced task evoked gamma-oscillation in prefrontal cortex. The voltage-gated sodium channel NaV1.1 is highly expressed in PV-positive interneurons, but only at low levels in principal cells. Positive modulators of Nav1.1 channels are for this reason considered potential candidates for the treatment of cognitive disorders. Here we examined the effect of the novel positive modulator of voltage-gated sodium channels Lu AE98134. We found that Lu AE98134 facilitated the sodium current mediated by NaV1.1 expressed in HEK cells by shifting its activation to more negative values, decreasing its inactivation kinetics and promoting a persistent inward current. In a slice preparation from the brain of adult mice, Lu AE98134 promoted the excitability of fast spiking interneurons by decreasing the threshold for action potentials. We then tested if Lu AE98134 could normalize the altered firing properties of FSINs in Dlx5/6+/- mutant mice. FSINs of this model for schizophrenia are characterized by broader action potentials and higher spike threshold. We found that in the presence of Lu AE98134, the firing frequency was increased while the spike duration and the threshold were decreased. Compounds with similar mode of action appear as promising candidates for restoring cognitive deficits present in schizophrenia. PMID- 28987819 TI - The in vivo anti-leukemia activity of N-(1-Pyrenlyl) maleimide in a bioluminescent mouse model. AB - In a search for anticancer drugs by screening for inhibitors of telomerase, we have identified several small-molecule inhibitors that selectively inhibit telomerase in a cell-free system. Among these inhibitors, N-(1-pyrenyl) maleimide (NPM) induced apoptosis and displayed the greatest differential cytotoxicity against acute T cell leukemia-derived Jurkat cells cultured in vitro. In this work, the in vivo anti-leukemia activity of NPM was investigated using a bioluminescent mouse model. The luciferase-expressing Jurkat cells (Jurkat-Luc) were mixed with matrigel and injected subcutaneously into the nude mice. Drug treatment was commenced on day 7 after tumor implantation. The growth of xenografted tumors was significantly inhibited in the mice treated with NPM, which is comparable to the inhibitory effect of a classical anti-leukemia drug, cyclophosphamide. Combined treatment with NPM and cyclophosphamide further enhanced the growth inhibition of xenografted Jurkat-Luc cells. Immunohistochemistry staining with cleaved caspase 3 (cl-caspase 3) indicated a very heavy staining of cl-caspase 3 only in the tumor implants excised from the NPM-treated mice. We conclude that NPM induced apoptosis and inhibited the growth of xenografted Jurkat-Luc cells in nude mice, demonstrating that NPM displays anti-leukemia activity in vivo. PMID- 28987818 TI - The anti-apoptotic effect of fluid mechanics preconditioning by cells membrane and mitochondria in rats brain microvascular endothelial cells. AB - Exercise preconditioning is a simple and effective way to prevent ischemia. This paper further provided the mechanism in hemodynamic aspects at the cellular level. To study the anti-apoptotic effects of fluid mechanics preconditioning, Cultured rats brain microvascular endothelial cells were given fluid intervention in a parallel plate flow chamber before oxygen glucose deprivation. It showed that fluid mechanics preconditioning could inhibit the apoptosis of endothelial cells, and this process might be mediated by the shear stress activation of Tie-2 on cells membrane surface and Bcl-2 on the mitochondria surface. PMID- 28987820 TI - Transfer of multidrug resistance among acute myeloid leukemia cells via extracellular vesicles and their microRNA cargo. AB - The treatment of acute leukemia is still challenging due in part to the development of resistance and relapse. This chemotherapeutics resistance is established by clonal selection of resistant variants of the cancer cells. Recently, a horizontal transfer of chemo-resistance among cancer cells via extracellular vesicles (EVs) has been suggested. The aim of this research was to investigate the role of EVs in chemo-resistance in acute myeloid leukemia. For this purpose, the sensitive strain of the promyelocytic leukemia HL60 cell line was studied along with its multi-resistant strain, HL60/AR that overexpresses the multidrug resistance protein 1 (MRP-1). A chemo-resistance transfer between the two strains was established by treating HL60 cells with EVs generated by HL60/AR. This study reveals that EVs from HL60/AR can interact with HL60 cells and transfer at least partially, their chemo-resistance. EVs-treated cells begin to express MRP-1 probably due to a direct transfer of MRP-1 and nucleic acids transported by EVs. In this context, two microRNAs were highlighted for their high differential expression in EVs related to sensitive or chemo-resistant cells: miR-19b and miR-20a. Because circulating microRNAs are found in all biological fluids, these results bring out their potential clinical use as chemo resistance biomarkers in acute myeloid leukemia. PMID- 28987822 TI - Metabolic response to hypoxia in European sea bass (Dicentrarchus labrax) displays developmental plasticity. AB - Several physiological functions in fish are shaped by environmental stimuli received during early life. In particular, early-life hypoxia has been reported to have long-lasting effects on fish metabolism, with potential consequences for fish life history traits. In the present study, we examine whether the synergistic stressors hypoxia (40% and 100% air saturation) and temperature (15 degrees and 20 degrees C), encountered during early life, could condition later metabolic response in European sea bass (Dicentrarchus labrax) juveniles. Growth rate and metabolic parameters related to carbohydrate and lipid metabolism in the liver were investigated at the juvenile stage under normoxic and chronic hypoxic conditions. Juvenile growth rates were significantly lower (p<1*10-6) under hypoxic conditions and were not improved by prior early-life exposure to hypoxia. Growth was 1.3 times higher (p<5*10-3) in juveniles reared at 15 degrees C during the larval stage than those reared at 20 degrees C, suggesting that compensatory growth had occurred. Early-life exposure to hypoxia induced higher (p<2*10-6) glycogen stores in juveniles even though there was no apparent regulation of their carbohydrate metabolism. In the liver of juveniles exposed to chronic hypoxia, lower glycogen content combined with stimulation of phosphoenolpyruvate carboxykinase gene expression and higher lactate concentration indicated a stimulation of the anaerobic glycolytic pathway. Furthermore, hypoxia only induced lower (p<1*10-3) lipid content in the liver of juveniles that had experienced 15 degrees C at the larval stage. The present study provides evidence that environmental conditions experienced during early life shape the metabolic traits of D. labrax with potential consequences for juvenile physiological performance. PMID- 28987821 TI - Low-dose lenalidomide plus cytarabine in very elderly, unfit acute myeloid leukemia patients: Final result of a phase II study. AB - Outcome for elderly patients with acute myeloid leukemia (AML) is extremely poor. Intensive induction chemotherapy is often unsuitable. Sixty-six newly diagnosed AML patients (median age: 76years), ineligible for standard therapy, were consecutively treated with low-dose lenalidomide (10mg/day orally, days 1-21) plus 10mg/m2 low-dose cytarabine, subcutaneously, twice a day (days 1-15) every six weeks, up to 6 cycles. Complete remission (CR) rate was 36.3% according to intention-to-treat. Responding patients had a longer median overall survival than non-responders (517 vs. 70days, P<0.001). The achievement of CR was not predicted by bone marrow blast count, cytogenetics, molecular markers, prior MDS, white blood cell count. Conversely, by studying the global gene expression profile, we identified a molecular signature, including 309 genes associated with clinical response (CR versus no CR). Based on the expression of a minimal set of 16 genes, we developed an algorithm to predict treatment response, that was successfully validated by showing an overall accuracy of 88%. We met the primary endpoint of the study, by beating the estimated successful CR rate (P1) fixed at 30%. Moreover, CR induced by this 2-drug combo was efficiently predicted by genetic profiling, identifying a biomarker that warrants validation in independent series. PMID- 28987823 TI - Vertebral marrow adipose tissue adipokines as a possible cause of intervertebral disc inflammation. PMID- 28987824 TI - Economic analysis of a nurse-led programme for comorbidities management of rheumatoid arthritis patients. AB - OBJECTIVES: Rheumatoid arthritis (RA) cause major functional, psychological, social and occupational repercussions for patients and has important economic consequences for society. The principal objective of this work was to determine the economic pertinence of a staff nurse specialised in preventive management for these patients. METHODS: The COMEDRA multicentre randomised controlled clinical trial, conducted from March 2011 to June 2012, showed the effectiveness of a nurse-led programme dedicated to the management of comorbidities trough the promotion of 11 preventive procedures. A cost-benefit analysis, from a societal perspective and based on direct medical cost, was conducted to assess the equivalence of the cost of the nurse-led programme and the cost of the additional preventive procedures performed, engendered by the programme. The programme was considered effective if its cost was less than or equal to the costs of the additional preventive procedures. The costs were calculated from the approved health insurance charges. From the total costs induced, a contributive share was measured, corresponding to the ratio of the total costs of each type of procedure to the overall total cost. RESULTS: The cost of the intervention was assessed at ?16,804.2. This intervention contributed to the performance of 747 additional preventive procedures, at a cost of ?30,184.8. This intervention with these patients is financially balanced when at least 37 patients follow the recommendations for every preventive procedure. CONCLUSIONS: From the hospital's perspective and from both a medical and economic point of view, a nurse-led programme to manage the comorbidities of RA is useful. PMID- 28987825 TI - Potential of connected devices to optimize cattle reproduction. AB - Estrus and calving are two major events of reproduction that benefit from connected devices because of their crucial importance in herd economics and the amount of time required for their detection. The objectives of this review are to: 1) provide an update on performances reached by sensor systems to detect estrus and calving time; 2) discuss current economic issues related to connected devices for the management of cattle reproduction; 3) propose perspectives for these devices. The main physiological parameters monitored separately or in combination by connected devices are the cow activity, body temperature and rumination or eating behavior. The combination of several indicators in one sensor may maximize the performances of estrus and calving detection. An effort remains to be made for the prediction of calvings that will require human assistance (dystocia). The main reasons to invest in connected devices are to optimize herd reproductive performances and reduce labor on farm. The economic benefit was evaluated for estrus detection and depends on the initial herd performances, herd size, labor cost and price of the equipment. Major issues associated with the use of automated sensor systems are the weight of financial investment, the lack of economic analysis and limited skills of the users to manage associated technologies. In the near future, connected devices may allow a precise phenotyping of reproductive and health traits on animals and could help to improve animal welfare and public perception of animal production. PMID- 28987826 TI - Orbital Compartment Syndrome After Frontotemporal Craniotomy: Case Report and Review of Literature. AB - INTRODUCTION: Orbital compartment syndrome (OCS) is a rare condition characterized by increased intraorbital pressure and hypoperfusion of critical neural structures. It is usually associated with external ophthalmoplegia. We report a case of postoperative OCS following a frontotemporal craniotomy and review pertinent literature. CASE DESCRIPTION: A 3-year-old female patient presented with a 3-year history of refractory epilepsy and diagnosis of right frontobasal cortical dysplasia. She underwent an elective frontotemporal craniotomy to allow resection of dysplastic cortex. The intraoperative period was uneventful. Postoperatively, following removal of operating fields, we noticed proptosis and right periorbital swelling. A diagnosis of orbital compartment syndrome was made. At the pediatric intensive care unit, the patient underwent an emergency right lateral canthotomy with wide inferior and superior cantholysis. Nowadays she is in the fourth month of postoperative follow-up. There is still slight and almost indistinguishable exophthalmos, but her extrinsic eye movement ranges and reaction to light are normal. DISCUSSION: OCS is a rare ophthalmologic emergency characterized by an acute rise in orbital pressure and may result in complete irreversible blindness if not rapidly treated. The frontotemporal or "pterional" craniotomy exposure requires a myocutaneous flap to be retracted anteriorly and inferiorly near the orbit. There may be orbital compression due to this flap leading to potential harmful complications. Attention to factors such as direct ocular pressure from skin flaps, congestion from head positioning, and adequate intraoperative eye protection may reduce the risk or allow faster management. PMID- 28987827 TI - Surgical Management of Giant Intracranial Meningioma: Operative Nuances, Challenges, and Outcome. AB - BACKGROUND: The giant intracranial meningioma (GIM) constitutes a different spectrum of brain tumors that invade the vital neurovascular structures, which makes the primary mode of treatment, surgery, a technically challenging one. The surgery for GIM is unique because of the large size of the tumor, prominent vascularity, entangling and limited visualization of various neurovascular structures, and severe cerebral edema. This study reports the authors surgical experience of 80 GIM cases, the operative challenges and surgical outcome. METHODS: A retrospective analysis of 80 patients with histologically proven meningioma (>=5 cm) who underwent surgical treatment at Louisiana State University Health Sciences Center (Shreveport, Louisiana, USA) over a 20-year period (1995-2015) is presented. The clinical and radiologic data were collected from the hospital database. The tumors were categorized into histologic groups according to World Health Organization (WHO) classification. The relevant statistical analysis of the study was conducted using SPSS software, version 22.0. RESULTS: The study included 27 male patients (33.8%) and 53 female patients (66.3%). The mean age of the cohort was 56 years (56.3+/-16.1). The mean size of the tumor was 56.4 +/-4 mm with a range from 50 mm to 84 mm. Skull base was the most common location of GIM (57 patients, 71.3%). Simpson grade 1 excision was achieved in 9 patients (11.3%), whereas grade 2 excision was achieved in 57 patients (71.3%); 80% of the tumors belonged to WHO grade 1. The operative mortality was seen in 4 patients (5%). Regression analysis showed that age, sex, location of the tumor, neuronavigation, Simpson grade of excision, and histology of tumor were the factors that significantly affected the recurrence-free survival (RFS). CONCLUSIONS: The surgery for GIM is unique in different ways. As surgery for GIM is formidable, radiologic characteristics can be useful adjuncts for planning an effective and safe surgical strategy. The factors such as young age, male sex, use of neuronavigation, and skull base location positively influenced RFS, whereas Simpson grade 3 or 4 and poor histologic grade adversely influenced RFS. A careful preoperative evaluation, understanding of the risk factors, effective surgical approach, and judicious use of intraoperative adjuncts are the key factors with pivotal roles in GIM resection. PMID- 28987828 TI - Acute Response of Neurons: An Early Event of Neuronal Cell Death After Facial Nerve Injury. AB - OBJECTIVE: To research the early acute response events of facial nerve injury. METHODS: Sixty male Sprague-Dawley rats were randomly divided into 2 groups. Facial nerve anastomosis was performed for rats in study group. Rats in control group underwent the same surgical procedure, but without cutting off the facial nerve. Before nerve anastomosis and at days 1, 3, 7, 14, and 28 after nerve anastomosis, 5 rats of each group were selected and right side brainstem tissue samples containing the facial nerve nucleus were obtained. Hematoxylin and eosin (H&E) staining and TUNEL detection was performed to observe facial neurons changes. Facial neurons mortality and apoptosis were studied. Expression of caspase-3, LC3, and Beclin1 was detected with Western blot assay. RESULTS: In study group on day 7 day after nerve anastomosis, Nissl body dissolution and apoptotic facial neurons were significantly increased, the typical polygonal shape and swollen cells disappeared, the number of facial neurons was significantly lower, and the number of apoptotic facial neurons was significantly higher (P < 0.01). In addition, facial neuron mortality rate was significantly increased at day 7, reaching the peak at day 14. Expression of caspase-3, LC3, and Beclin1 was also significantly up-regulated after nerve anastomosis. CONCLUSION: Nissl body dissolution, typical polygonal shape disappearing, cell swelling, facial neuron mortality and apoptosis, and up-regulated expression of caspase-3, LC3, and Beclin1 are the early events of cell death after facial nerve injury, which are the important precursors to facial nerve injury. PMID- 28987829 TI - Big Data and Clinical Research in Traumatic Brain Injury. PMID- 28987830 TI - Intracranial Meningioma in Patients Age <35 Years: Evolution of the Disease in the Era of Human Immunodeficiency Virus Infection. AB - BACKGROUND: Intracranial meningiomas are most common among patients in their fifth to seventh decade of life and rare in children and young adults. They constitute 1.5% of all neoplasms in patients age <20 years, but account for 13.5% of all neoplasms in patients age 20-34 years. They are often associated with hereditary or familial syndromes in children and young adults, and tend to be of high grade. Here we describe the histopathological subtypes of intracranial meningioma between human immunodeficiency virus 1 (HIV-1)-seropositive patients and the general population with intracranial meningiomas 35 years old and younger. METHODS: Data were collected from all consecutive patients age <=35 years diagnosed with intracranial meningioma between May 2003 and May 2015. Age was categorized as <20 years, 21-30 years, and >30 years. Histopathological grade was classified according to the 2000 World Health Organization (WHO) grading system as grade I, II, or III. Patients were grouped into an HIV-1-seropositive group and the general population, presumed seronegative. WHO grade II/III meningioma represented high-grade meningioma. RESULTS: HIV-1-seropositive status was associated with increased risk of the development of high-grade (WHO grade II/III) meningioma (odds ratio, 2.9; 95% confidence interval, 1.06-8.09; P = 0.04) compared with the general population of patients with meningiomas. No significant associations were found between WHO grade and age, sex, ethnicity/race, or location. CONCLUSIONS: Intracranial meningiomas in young HIV-1 positive patients tend to be of high grade; therefore, conservative or noninvasive therapies should be offered with caution and only after tissue diagnosis has confirmed benign WHO grade. PMID- 28987831 TI - Agenesis of Anterior Falx Cerebri in Patient with Planned Interhemispheric Approach to Third Ventricle Mass. AB - BACKGROUND: Complete or partial agenesis of the falx cerebri may occur in pediatric patients with developmental anomalies. However, isolated agenesis of the falx in a developmentally normal adult is exceptionally rare. We describe the first reported case of a patient with a third ventricular mass associated with partial agenesis of the anterior falx cerebri, a circumstance that influenced surgical access to a third ventricular epidermoid cyst. CASE DESCRIPTION: A 60 year-old developmentally normal woman presented with progressively worsening aphasia and altered mental status. Brain magnetic resonance imaging showed obstructive hydrocephalus from a third ventricular mass. An anterior interhemispheric transcallosal approach was planned to remove the tumor. However, upon dural opening there was no evidence of a falx cerebri, an anomaly visible but not reported on the prior imaging studies. An interhemispheric fissure was present, but the medial frontal lobes were densely adherent, with multiple traversing veins within the superficial arachnoid of the fissure. Therefore, a left frontal transcortical approach was performed for microsurgical resection of the tumor. Histopathologic analysis identified the lesion to be an epidermoid cyst. CONCLUSIONS: Partial agenesis of the falx cerebri is exceedingly rare in a developmentally normal adult, particularly in the presence of an anatomically normal superior sagittal sinus. If present, however, it is important to note this association preoperatively because partial agenesis of the falx cerebri precludes an interhemispheric transcallosal approach to the lateral and third ventricles. PMID- 28987832 TI - Postoperative Cerebral Ischemia Due to Hypotension in Moyamoya Patient with Autonomic Dysfunction. AB - BACKGROUND: Hypotension is a significant risk factor for the development of ischemic complication following revascularization surgery for moyamoya disease (MMD). However, it is currently unknown whether autonomic dysfunction also plays a role. CASE DESCRIPTION: Here we report a case of MMD in which hypotension due to autonomic dysfunction caused postoperative cerebral ischemia. A 30-year-old female patient with MMD had a history of transient right hemiparesis following laughter. Single-photon emission computed tomography showed impaired cerebral blood flow (CBF) in both cerebral hemispheres, so she underwent revascularization surgery in her left cerebral hemisphere. She awoke from anesthesia uneventfully; however, 1 hour after the surgery her blood pressure suddenly dropped to 90/40 mm Hg and she became comatose. A perfusion computed tomography scan demonstrated a widespread reduction in CBF in the left hemisphere. Bezold-Jarisch reflex was thought to be the cause of the hypotension. Following treatment with a vasopressor agent, her BP increased and her consciousness rapidly recovered. The reduced CBF had almost completely recovered the next day. Head-up tilt test conducted 2 weeks after surgery demonstrated latent vasopressor-type autonomic dysfunction, which was possibly another cause of the hypotension. She was discharged from the hospital, and the laughter-induced hemiparesis gradually resolved. CONCLUSION: Situational neurologic deterioration in patients with MMD suggests latent autonomic dysfunction, which may be a risk factor for postoperative ischemic complications. PMID- 28987833 TI - Training of Intra-Axial Brain Tumor Resection Using a Self-Made Simple Device with Agar and Gelatin. AB - INTRODUCTION: Self-made devices composed of agar and gelatin gel were used for resident training in intra-axial brain tumor resection. The mixture gel of agar and gelatin is retractable and can be suctioned. Hardness of the gel depends on the concentration of the solution. Therefore, by changing the concentration, it is easy to make gels of various hardness. METHODS: In this study, a mass of gel that looked like a tumor was placed into another gel that looked like the brain. A part of the "brain" was regarded as the eloquent area. Three types of "tumor" were prepared: hard, moderately hard, and soft tumors. Residents tried to remove the tumor entirely with minimal brain invasion. The training was repeated with 3 types of gel. After resection, the weight of the residual tumor, resected normal brain, and resected eloquent area were measured, and the time taken for removal was recorded. RESULTS: These data were compared between residents and neurosurgeons. We also analyzed how these data improved with repeated practice. In most cases, residual tumor, resected normal brain, resected eloquent area, and time taken for removal were less in neurosurgeons than in residents. Repeated training made residents more skillful. The responses of the trainees were almost all favorable. CONCLUSIONS: Our devices with "tumors" of various hardness appear to be suitable for resident training in each surgical skill. For the next step of this study, we will attempt to fabricate more practical 3-dimensional gel models for presurgical simulation. PMID- 28987834 TI - Subtemporal Approach for Gross Total Resection of Retrochiasmatic Craniopharyngiomas: Our Experience on 30 Cases. AB - BACKGROUND: Surgical treatment of retrochiasmatic craniopharyngiomas is associated with higher rates of complications, mortality, failure of complete removal, and recurrence compared with craniopharyngiomas located elsewhere. These tumors lie behind the optic chiasm and when large can extend upward into the third ventricle and downward along the brain stem, making their adequate exposure challenging. Most of the proposed techniques either use a translamina terminalis route or require wide bony exposures. In this study, we assessed the feasibility of a subtemporal approach for achieving gross total resection of retrochiasmatic craniopharyngiomas. METHODS: Thirty patients with retrochiasmatic craniopharyngioma underwent surgery via a subtemporal approach. The technique and surgical and preoperative and postoperative endocrinologic outcomes are described in detail. RESULTS: Gross total resection was achieved in all cases. The average tumor volume was 7.59 mL. The average postsurgical observation time was 73.8 months. During this time, 3 recurrences were observed (10.7%). The perioperative mortality was 6.6%. The pituitary stalk was preserved in 13 cases. Partial preservation of the pituitary stalk did not offer any advantage in terms of pituitary function. No postoperative vision worsening or new fixed neurologic deficits were observed. Among the 22 patients with preoperative vision impairment, 18 reported a significant improvement. The most common abnormalities within the temporal lobe on the side of the exposure seen on control magnetic resonance imaging were mild temporal horn enlargement (13 cases) and T2 hyperintensity (7 cases). CONCLUSIONS: A subtemporal approach can be an attractive alternative approach to accessing retrochiasmatic craniopharyngiomas. Outcomes are comparable to those associated with other widely used and time consuming exposures. PMID- 28987835 TI - Quality and Quantity of Memories in Patients Who Undergo Awake Brain Tumor Resection. AB - BACKGROUND: Awake craniotomy is performed with increasing frequency for brain tumor surgery in eloquent areas; however, little is known about patients' memories of this procedure. Here we retrospectively analyzed the quality and quantity of memories in a series of patients treated following a standardized protocol. METHODS: We treated 61 consecutive patients within 3 years, 48 of whom were alive when the study was performed. Each of these patients received a questionnaire eliciting information about their perioperative memories and perceptions. The perioperative process was broken down into steps, and for each step the patient was to judge the quantity (nothing-everything) and quality (very negative-very positive) of his or her memories. RESULTS: Thirty-six of the 48 patients completed the questionnaire (75%). The quantity of memories was quite incomplete, even for intraoperative moments when patients were awake and cooperative. On average, the quality of memories was neutral or positive. A higher quantity of memories was associated with a higher quality of memories. The most commonly reported sources of discomfort were placement of the Mayfield clamp, followed by laying on the operating room table with movement restriction, and irritation by the urinary catheter in situ. CONCLUSIONS: Awake craniotomy can be performed following our protocol in such a way that it is experienced as (very) comfortable. However, there are moments of discomfort, which can be managed by the team. Extensive preoperative preparation may be considered a crucial part of the procedure. Less amnesia seems to improve patient satisfaction. The results of this study can help guide protocol optimization, expectation management, and information for future patients. PMID- 28987836 TI - Successful Surgical Resection of Spinal Artery Aneurysms: Report of 3 Cases. AB - BACKGROUND: Spinal artery aneurysms (SAAs) are extremely rare lesions that can occur in isolation or associated with vascular malformations. Herein, we present 3 unusual cases of SAAs and discuss imaging, diagnosis, and surgical management strategies. CASE DESCRIPTION: The first patient was a 57-year-old woman who presented with sudden onset of severe headache. Spinal angiography demonstrated an isolated anterior spinal artery (ASA) aneurysm at the level of the craniocervical junction. The second patient was a 27-year-old woman who presented with progressive bilateral pain of her lower limbs. The result of spinal angiography was consistent with an aneurysm at the level of L1. The third patient was a 26-year-old man who presented with bilateral weakness and numbness of the lower limbs. Spinal angiography revealed a conus medullaris aneurysm associated with an arteriovenous malformation (AVM). All these lesions were successfully managed with clipping or resection, and good outcomes were achieved. CONCLUSION: Spinal artery aneurysms are rare lesions. Herein, we report 3 such cases and emphasize the importance of surgical management. PMID- 28987837 TI - Physiologic Growth Hormone-Replacement Therapy and Craniopharyngioma Recurrence in Pediatric Patients: A Meta-Analysis. AB - OBJECTIVE: A systematic review and meta-analysis were conducted to examine the effect of growth hormone-replacement therapy (GHRT) on the recurrence of craniopharyngioma in children. METHODS: PubMed, Embase, and Cochrane databases were searched through April 2017 for studies that evaluated the effect of GHRT on the recurrence of pediatric craniopharyngioma. Pooled effect estimates were calculated with fixed- and random-effects models. RESULTS: Ten studies (n = 3487 patients) met all inclusion criteria, including 2 retrospective cohorts and 8 case series. Overall, 3436 pediatric patients were treated with GHRT after surgery and 51 were not. Using the fixed effect model, we found that the overall craniopharyngioma recurrence rate was lower among children who were treated by GHRT (10.9%; 95% confidence interval 9.80%-12.1%; I2 = 89.1%; P for heterogeneity <0.01; n = 10 groups) compared with those who were not (35.2%; 95% confidence interval 23.1%-49.6%; I2 = 61.7%; P for heterogeneity = 0.11; n = 3); the P value comparing the 2 groups was <0.01. Among patients who were treated with GHRT, subgroup analysis revealed that there was a greater prevalence of craniopharyngioma recurrence among studies conducted outside the United States (P < 0.01), single-center studies (P < 0.01), lower impact factor studies (P = 0.03), or studies with a lower quality rating (P = 0.01). Using the random effects model, we found that the results were not materially different except for when stratifying by GHRT, impact factor, or study quality; this led to nonsignificant differences. Both Begg's rank correlation test (P = 0.7) and Egger's linear regression test (P = 0.06) indicated no publication bias. CONCLUSIONS: This meta-analysis demonstrated a lower recurrence rate of craniopharyngioma among children treated with GHRT than those who were not. PMID- 28987839 TI - Lumbar Disk Arthroplasty for Degenerative Disk Disease: Literature Review. AB - Low back pain is the principal cause of long-term disability worldwide. We intend to address one of its main causes, degenerative disk disease, a spinal condition involving degradation of an intervertebral disk. Following unsuccessful conservative treatment, patients may be recommended for surgery. The two main surgical treatments for lumbar degenerative disk disease are lumbar fusion: traditional standard surgical treatment and lumbar disk arthroplasty, also known as lumbar total disk replacement. Lumbar fusion aims to relieve pain by fusing vertebrae together to eliminate movement at the joint, but it has been criticized for problems involving insignificant pain relief, a reduced range of motion, and an increased risk of adjacent segment degeneration. This leads to development of the lumbar total disk replacement technique, which aims to relieve pain replacing a degenerated intervertebral disk with a moveable prosthesis, thus mimicking the functional anatomy and biomechanics of a native intervertebral disk. Over the years a large range of prosthetic disks has been developed. The efficacy and current evidence for these prostheses are discussed in this review. The results of this study are intended to guide clinical practice and future lumbar total disk replacement device choice and design. PMID- 28987838 TI - Contralateral Approach to Middle Cerebral Artery Aneurysms: An Anatomical Clinical Analysis to Improve Patient Selection. AB - BACKGROUND: A contralateral approach to aneurysm clipping in cases of bilateral middle cerebral artery (MCA) aneurysms reduces surgical time and cost. However, there is a lack of evidence for objective patient selection. In this study, we assessed the change in surgical freedom along the contralateral MCA to provide objective evidence for patient selection. METHODS: Sixteen cadaveric specimens were studied. Through a pterional approach, the surgical freedom was calculated moving distally along the contralateral MCA in 5-mm increments. In addition, in a series of 19 MCA aneurysms clipped contralaterally by the senior author, the average length of the MCA from its origin to the aneurysm neck was measured on angiography. RESULTS: In these patients treated via a contralateral approach, the average length of the MCA segment from its origin to the aneurysm neck was 12.4 mm. Starting at the MCA origin, surgical freedom decreased significantly between all adjacent target points except at 5-10 mm from the MCA origin. CONCLUSIONS: After the proximal 5 mm, there is no significant decrease in surgical maneuverability within the proximal 10 mm of MCA when approached contralaterally. When compared to the average length of the MCA from its origin to the aneurysm neck in the clinical series, it can be concluded that the first 10 mm (average, 12.4 mm) of the contralateral MCA may be considered a surgical comfort zone for a contralateral approach. This criterion may be useful for patient selection for a contralateral approach in cases of multiple bilateral intracranial aneurysms. PMID- 28987841 TI - Severe Subarachnoid Hemorrhage Due to Fusiform Lateral Anterior (A1) Artery Perforator Aneurysm with "Spontaneous Resolution". AB - Perforating arteries are thin and long vessels which originate from the main cerebral arteries. Subarachnoidal hemorrhage from a perforator aneurysm is rare. Here, we report on a 70-year-old woman who presented with severe subarachnoid hemorrhage from a fusiform lateral anterior (A1) artery perforator aneurysm. Unexpectedly, digital subtraction angiography was non-diagnostic. MR imaging, however, demonstrated occlusion of the aneurysm secondary to thrombosis. Surgery was performed to remove the associated hematoma, and histopathological examination verified intraaneurysmal thrombosis. PMID- 28987840 TI - Endovascular Treatment of Ruptured Vertebrobasilar Dissecting Aneurysms Using Flow Diversion Embolization Devices: Single-Institution Experience. AB - OBJECTIVE: Treatment of ruptured posterior circulation dissecting aneurysms is technically challenging with potentially high morbidity and mortality. We sought to assess the safety and feasibility of using a flow-diversion device (FDD) and a specific acute antiplatelet aggregation protocol in the management of ruptured dissecting aneurysms. METHODS: Subjects with ruptured dissecting aneurysms treated during a 3-year period were retrospectively identified from a prospective registry. Intraoperative complications, morbidity, and mortality were recorded. Tirofiban maintenance infusion without bolus was administered intravenously immediately after deployment of the FDD, and almost all patients were loaded with dual antiplatelet (aspirin and clopidogrel) post procedure. Clinical follow-up evaluation and modified Rankin Scale were assessed. RESULTS: Nine subjects with ruptured posterior circulation dissecting aneurysms were treated with an FDD: 5 vertebral artery, 2 basilar artery, and 2 posterior inferior cerebellar artery aneurysms. Average World Federation of Neurosurgical Societies score was 2 (range 1-5). Seven patients had external ventricular drain placed acutely for hydrocephalus. Eight patients received tirofiban infusion without bolus after FDD. No intraoperative complications occurred. Two subjects developed asymptomatic intraparenchymal hemorrhage found on surveillance noncontrast computed tomography. One subject suffered a major intraparenchymal hemorrhage and died a few days post intervention after additional anticoagulation was started for a left ventricular assist device. Follow-up modified Rankin Scale within 12 months was 0 in 3 subjects, 1 in 3 subjects, 2 in 1 subject, and 4 in 1. CONCLUSIONS: Treatment of dissecting posterior circulation aneurysms with FDDs is feasible and a potential alternative to deconstructive techniques. PMID- 28987843 TI - The Endoscopic Buccal Fat Pad Flap for Closure of Skull Base Defects: A Report of 5 Cases. AB - OBJECTIVE: To demonstrate the clinical utility of the buccal fat pad flap (BFPF) for closing a variety of skull base defects. METHODS: A retrospective chart review of 5 consecutive patients who underwent endoscopic cranial base surgery with endoscopic harvest of BFPF pedicled along the internal maxillary artery for reconstruction of the skull base between October 2013 and November 2014. RESULTS: All 5 patients had complete take of the BFPFs with mucosalization on postoperative follow-up with no reported complications or cerebrospinal fluid leak. CONCLUSIONS: This is the first report on the application of endoscopic BFPF. Our experience suggests that this recently described flap is viable and a useful addition to the armamentarium of the skull base surgeon. PMID- 28987842 TI - Postnatal Management of Myelomeningocele: Outcome with a Multidisciplinary Team Experience. AB - INTRODUCTION: Myelomeningocele (MMC) is a complex neural tube defect. Few studies report the results of modern postnatal management. The goal of this study was to report the long-term outcome of a multidisciplinary approach of patients with MMC. METHODS: Forty-six MMCs were included. Clinical status was evaluated prospectively. RESULTS: Mean follow-up was 8.1 years. The level of the malformation was sacral or lower lumbar (<=L4) in 27 cases, higher lumbar (between L1 and L3) in 5 cases, and thoracic in 14 cases. A Chiari II malformation was present at birth in 78.3% of the cases. Seventy-six percent of the patients were operated on within the first 24 hours of life. Sixty-one percent needed a cerebrospinal fluid diversion procedure. Seven patients underwent a second surgery for a retethering of the spine. Eighty percent presented with orthopedic problems. Sixty-five percent of our patients were able to walk. Only 13% of patients had a normal urinary elimination. Two groups of patients were identified: one group with a malformation at the level of L4 or below (group 1) and another group with a malformation strictly above L4 (group 2). Group 1 had significantly better outcome. CONCLUSIONS: This series proves that modern multidisciplinary postnatal management of MMC is effective. In the light of these results and of the results of prenatal management of MMC, prenatal surgery seems to be a highly valuable tool to improve the outcome of patients with high lesions (level >=L3). PMID- 28987844 TI - Extraforaminal Discal Cyst as Cause of Radiculopathy. AB - We report the first extraforaminal location of a lumbar discal cyst. The patient was treated by hemilaminectomy, arthrectomy, cyst resection, and unilateral arthrodesis, achieving complete release of the nerve root. Extraforaminal lumbar discal cyst may represent an unexpected cause of sciatic pain with favorable outcome after surgical resection. PMID- 28987845 TI - Recurrent Cerebral Hemorrhage in Normal Pregnancy Secondary to Mycotic Pseudoaneurysms Related to Choriocarcinoma. AB - BACKGROUND: Choriocarcinoma coexisting with or after normal pregnancy is extremely rare. To our knowledge, our case report is the first time cerebral mycotic pseudoaneurysms from choriocarcinoma have been proven angiographically. CASE DESCRIPTION: A 38-week pregnant 26-year-old woman presented with an acute left frontal hemorrhage. She underwent emergency cesarean section, followed by hematoma evacuation and resection of what grossly appeared to be a medium-sized arteriovenous malformation at the time of surgery. Angiogram before and after resection showed no obvious vascular pathology. One month later, she returned with status epilepticus, and an acute parenchymal hematoma posterior to the surgical resection cavity was identified. Angiography showed a multilobulated pseudoaneurysm along the left middle cerebral artery. This was resected and found on histopathology to have choriocarcinoma within and around the blood vessels. Serum human chorionic gonadotrophin levels increased daily. Pan computed tomography showed a left lung lobular mass. The diagnosis was stage 4 World Health Organization score 9 high-risk metastatic choriocarcinoma requiring radiation followed by multiagent chemotherapy. Two weeks later, she had another seizure. An angiogram showed an unruptured pseudoaneurysm along the right posterior cerebral artery, which was embolized. CONCLUSIONS: Metastatic choriocarcinoma is rarely considered during a viable pregnancy but is almost always fatal if unrecognized. Early recognition enhances the chances of cure with chemotherapy. Arteriovenous malformations are typically considered in young women with intracerebral hemorrhages and have higher risk of rupture in pregnant women, but physicians should also be aware of metastatic choriocarcinoma and the development of mycotic aneurysms in peripartum women with intracerebral hemorrhages. PMID- 28987846 TI - Surgery and Radiotherapy for Symptomatic Spinal Metastases Is More Cost Effective Than Radiotherapy Alone: A Cost Utility Analysis in a U.K. Spinal Center. AB - BACKGROUND: Surgery for symptomatic spinal metastases is effective at prolonging ambulation and life, but it can appear costly at first glance. We have studied the difference between the cost of surgery and reimbursement received, and the cost-effectiveness of surgery in a U.K. tertiary referral spinal center. METHODS: A cost-versus-reimbursement and cost-utility analysis was performed in a prospective cohort of patients admitted for surgical treatment of spinal metastases. Outcome measures were health-related quality of life using the EuroQol EQ-5D-3L, Frankel score, quality-adjusted life years (QALYs), and treatment and reimbursement costs. RESULTS: One hundred thirty consecutive patients were prospectively recruited, of whom 92 had information available for cost and reimbursement comparison, and 100 had information to complete cost utility analysis. Median cost of hospital treatment per patient was L20,752; median reimbursement received was L18,291, with a median shortfall of L1,967. Surgery in addition to radiotherapy over a lifetime horizon was both more effective and less costly than radiotherapy alone, and therefore was found to be cost-effective. CONCLUSIONS: Our results demonstrate that reimbursement to hospitals for surgical management of symptomatic spinal metastases in the United Kingdom is broadly in line with costs, and that there was an overall saving as a result of community care costs being mitigated by patients walking for longer, which is within the expected National Health Service threshold. Surgery for metastatic spinal tumors is effective and a good value for the money. PMID- 28987847 TI - Mikulicz Disease Mimicking Intraorbital Tumors. AB - We report a case of Mikulicz disease (MD), an immunoglobulin G4 (IgG4)-related disease that affects the lacrimal and salivary glands. IgG4-related disease is a relatively new clinical entity and is not commonly encountered by neurosurgeons. MD sometimes mimics intraorbital tumors such as malignant lymphoma but responds well to corticosteroid treatment. Thus it is important to recognize the clinical and radiographic features of MD. PMID- 28987848 TI - Prevention and Treatment of Hyponatremia in Patients with Subarachnoid Hemorrhage: A Systematic Review. AB - BACKGROUND: Current guidelines for the management of hyponatremia in patients with subarachnoid hemorrhage (SAH) are not based on a systematic assessment of the literature. We evaluated published studies on the efficacy and safety of current preventative and treatment strategies for hyponatremia in patients with SAH. METHODS: We searched the Cochrane Central Register of Controlled Trials, Embase, MEDLINE, and PubMed for relevant studies. Primary outcomes of interest included neurologic functional outcomes, symptomatic vasospasm, and others. Secondary outcomes included measures of sodium and volume status. RESULTS: We included 5 out of 117 identified studies: 1 before-and-after observational trial (using fludrocortisone) and 4 randomized controlled trials (2 using fludrocortisone; 2 using hydrocortisone). All 5 trials had a high risk of bias in at least 1 domain. We could not perform a meta-analysis of functional outcomes; however, individual studies did not demonstrate statistically significant differences. Mineralocorticoid use did not statistically significantly reduce the incidence of symptomatic vasospasm (relative risk, 0.60; 95% confidence interval, 0.35-1.03; I2 = 0%). The studies did not report other primary outcomes. In the 4 RCTs, mineralocorticoid use reduced natriuresis and volume contraction. CONCLUSIONS: Current evidence does not demonstrate a benefit of preventative treatment with mineralocorticoids in clinically important outcomes, although a difference cannot be ruled out due to imprecision. Larger well-designed trials are needed to establish the impact of mineralocorticoids and fluid and sodium supplementation strategies on clinically relevant outcomes in the prevention and treatment of hyponatremia in patients with SAH. PMID- 28987849 TI - World Health Organization Grade II Meningiomas: The Role of Adjuvant/Salvage Gamma Knife Surgery After Initial Surgery and Prognostic Factor Assessment. AB - OBJECTIVE: This study was performed to evaluate the efficiency of Gamma Knife surgery (GKS) on reducing recurrence of World Health Organization (WHO) grade II meningiomas after surgery and to define the risk factors associated with tumor recurrence/progression and patient's death. METHODS: This retrospective study included 75 patients who were diagnosed with WHO grade II meningiomas after initial surgery. The Kaplan-Meier method with a log-rank test was used to calculate the survival curves. Univariate and multivariate Cox proportional hazards model were used to identify the risk factors associated with tumor recurrence/progression and patient's death. RESULTS: The median follow-up period was 70 months. The overall survival (OS) was 97.2% at 2 years and 89.8% at 5 years. The progression-free survival (PFS) at 1, 3, and 5 years was 89.3%, 72.6%, and 59.3%, respectively. Comparing the effects on PFS and OS between different groups, there were no statistically significant differences between the surgery alone group and the surgery with adjuvant/salvage GKS group (P = 0.512; P = 0.949). In multivariate Cox proportional hazards model analysis, extent of resection (P = 0.001) and tumor location (P = 0.015) were associated with tumor recurrence; only histologic subtypes (P = 0.005) were associated with patient's death. CONCLUSIONS: There was no significant PFS or OS benefit for patients with WHO grade II meningiomas treated with adjuvant/salvage GKS postoperatively. Convexity meningiomas with gross total resection tended to benefit PFS. We suggest trying to achieve maximum safe gross total resection for patients with WHO grade II meningiomas, then following up closely. PMID- 28987850 TI - Suturing and Dural Wrapping for a Blood Blister-Like Aneurysm on the Supraclinoid Segment of the Internal Carotid Artery due to Dissection. AB - BACKGROUND: Internal carotid artery (ICA) reconstruction is still the most effective treatment for a blood blister-like aneurysm (BBA) on the supraclinoid segment of the ICA, and clipping after wrapping has the most precise effects. However, the materials used are most often artificial. This study examined the use of autologous dura to replace the artificial materials used for wrapping after suturing a BBA. CASE DESCRIPTION: A 38-year-old man was hospitalized for subarachnoid hemorrhage. Computed tomography angiography of the head and digital subtraction angiography showed a BBA on the dorsal supraclinoid segment of the ICA. A right frontotemporal craniotomy with extradural resection of the anterior clinoid was adopted. The aneurysm was trapped with temporary clips and was found to be derived from dissection of the ICA. The separated adventitia and vascular wall were sutured to reconstruct the vascular wall first, and then the dura was cut and shaped to wrap the supraclinoid segment of the ICA. The dura was sutured onto the ICA wall to prevent dislocation. A 6-month follow-up digital subtraction angiography review showed that the supraclinoid segment of the ICA was well reconstructed, the vascular cavity exhibited slight stenosis, and BBA did not recur. Postoperative follow-up magnetic resonance imaging showed satisfying images. CONCLUSIONS: The method we adopted is new and showed satisfactory curative results, suggesting that ICA suturing with dura mater wrapping may become a method for the treatment of a BBA on the supraclinoid segment. The dura could potentially replace the artificial materials used for wrapping the ICA. PMID- 28987851 TI - Effect of Single-Level Transforaminal Lumbar Interbody Fusion on Segmental and Overall Lumbar Lordosis in Patients with Lumbar Degenerative Disease. AB - OBJECTIVE: To investigate the ability of transforaminal lumbar interbody fusion (TLIF) to improve lumbar lordosis (LL). METHODS: In this retrospective study, 92 patients undergoing single-level TLIF to treat lumbar degenerative disease were divided into a low back pain, radiculopathy, and neurogenic claudication group according to their symptoms. Preoperative and postoperative measures, including segmental LL, whole LL, pelvic incidence (PI), pelvic tilt, thoracic kyphosis, sagittal vertical axis, visual analog scale for back and leg pain, and Oswestry Disability Index, were used to evaluate radiographic and clinical outcomes. RESULTS: All clinical parameters were significantly improved after TLIF. There was no significant difference in any radiographic parameters in the low back pain group. In the radiculopathy and neurogenic claudication groups, all radiographic parameters were significantly changed after TLIF except for segmental LL and PI in both groups and pelvic tilt in the radiculopathy group. No statistically significant differences were found in improvement of segmental LL, PI, thoracic kyphosis, and visual analog scale (leg) between the radiculopathy and neurogenic claudication groups, whereas the differences in improvement of whole LL, pelvic tilt, PI-LL, sagittal vertical axis, visual analog scale (back), and Oswestry Disability Index were significant between the 2 groups. CONCLUSIONS: For patients with neurogenic leg symptoms owing to single-level lumbar degenerative disease, whole LL was improved after TLIF as a result of spontaneous restoration of lordosis at the unfused lumbar levels. PMID- 28987852 TI - Factors Associated with 90-Day Outcomes of Patients with Acute Posterior Circulation Stroke Treated By Mechanical Thrombectomy. AB - BACKGROUND AND OBJECTIVE: Early recanalization of acute posterior circulation stroke caused by large intracranial vessel occlusion by mechanical thrombectomy with stent retrievers may improve the outcome of patients. However, evidence of patient selection is still lacking. This study investigated the prognostic factors of acute posterior circulation stroke caused by large intracranial arterial occlusion when treated with stent-retriever thrombectomy. METHODS: A total of 69 patients from March 2012 to November 2016 were included in the study. These patients presented with acute posterior circulation stroke caused by large intracranial vessel occlusion and underwent mechanical thrombectomy with Solitaire AB or combined with additional balloon and/or stenting angioplasty. Baseline characteristics, clinical course, and imaging data of the patients were analyzed. Good clinical outcome (defined as a modified Rankin Scale score of 0-2 at 90 days) and safety outcome (defined as death within 90 days after thrombectomy) were considered as end points. The association between factors with good clinical outcome and safety outcome was evaluated with both logistic regression and receiver operating characteristic curve analyses. RESULTS: Of the 69 patients, mean age was 59 years (standard deviation, 8 years) and men comprised 82.6% (57/69). The median onset-to-treatment time was 360 minutes (interquartile range, 250-537 minutes). The median National Institutes of Health Stroke Scale (NIHSS) score was 25 (interquartile range, 17-30) on admission. Successful recanalization was achieved in 62 of the 69 cases (89.9%) and 36.2% (25/69) were independent at 90 days. Regression analysis showed that stroke subtype (intracranial atherosclerotic disease vs. embolism; odds ratio [OR], 0.101; 95% confidence interval [CI], 0.020-0.501; P = 0.005), baseline NIHSS score (>=22 vs. <22; OR, 0.157; 95% CI, 0.040-0.614; P = 0.008) and posterior circulation Acute Stroke Prognosis Early CT Score (pc-ASPECTS) on diffusion weighted imaging [DWI] (weighted magnetic resonance imaging) before thrombectomy (>=6 vs. <6; OR, 7.335; 95% CI, 1.495-36.191; P = 0.014) were independent predictive factors of good clinical outcome, respectively at 90 days, whereas high NIHSS score (>=30 vs. <30; OR, 5.569; 95% CI, 1.573-19.716; P = 0.008) and collateral status (>=2 vs. <2; OR, 0.210; 95% CI, 0.059-0.752; P = 0.016) before treatment were associated with mortality at 90 days. Based on receiver operating characteristic curves, baseline NIHSS score (area under the curve [AUC] = 0.779; cutoff, >=22; P < 0.001; sensitivity, 72%; specificity, 77.3%), pc-ASPECTS on DWI (AUC = 0.820; cutoff, >=6; P < 0.001; sensitivity, 72%; specificity, 77.3%) before treatment were independent indicators predicting good clinical outcome at 90 days. Increased risk of death by 90 days was associated with baseline NIHSS score (AUC = 0.719; cutoff, >=30; P = 0.007; sensitivity, 64.7%; specificity, 78.9%) and worse collateral status (AUC = 0.820; cutoff, >=2; P < 0.001; sensitivity, 58.8%; specificity, 80.8%) before treatment. CONCLUSIONS: Stroke subtype, initial stroke severity, and pc-ASPECTS on DWI as well as collateral status before thrombectomy are independent factors affecting the clinical outcome in patients treated with Solitaire AB thrombectomy for acute posterior circulation stroke caused by large intracranial vessel occlusion. PMID- 28987853 TI - Early Hemodynamic Changes Based on Initial Color-Coding Angiography as a Predictor for Developing Subsequent Symptomatic Vasospasm After Aneurysmal Subarachnoid Hemorrhage. AB - INTRODUCTION: Prediction of vasospasm after aneurysmal subarachnoid hemorrhage (aSAH) remains imperfect and currently relies on clinical and radiographic characteristics. Whether early hemodynamic changes may refine risk stratification for delayed vasospasm (DV) after aSAH was analyzed. METHODS: Patients with aSAH (n = 53) and a control group with unruptured intracranial aneurysms (UIA) (n = 12) with initial color-coding angiography at admission were included in this study (n = 65). Clinical and radiologic data were collected, and uni- and multivariate analysis was used to correlate the occurrence of DV (manifesting clinically or detected with transcranial Doppler or angiography) with hemodynamic features of the initial angiography including Tmax and mean transit times (MTTs). RESULTS: In the aSAH patient cohort, 37 of 53 patients with aSAH (70%) developed DV. After we controlled for the effects of age, Hunt and Hess grade, and modified Fisher grade, patients with DV had a shorter mean region of interest peak time (Tmax) of the anterior cerebral artery A2 segment (P = 0.036) and the middle cerebral artery M1 (P = 0.045) and M3 (P = 0.013) segments. Mean MTTs between internal carotid artery to middle cerebral artery M3 segment (P = 0.026) was also significantly shorter in patients with DV when compared with controls. CONCLUSIONS: Tmax and MTT on angiography within 48 hours of aneurysm rupture before treatment provide an early quantitative assessment in patients with aSAH and in this small study were predictive for the development of subsequent symptomatic DV. Early identification of patients with aSAH at greatest risk of DV may ameliorate clinical outcome through timely, selective implementation of aggressive prophylactic therapy to prevent the effects of DV. PMID- 28987854 TI - Contact Aspiration with the New ARC Catheter for Thrombectomy of Acute Ischemic Stroke: Single-Center Results. AB - BACKGROUND/OBJECTIVE: Contact aspiration has gained growing acceptance in endovascular stroke therapy. The safety and efficacy data of the novel ARC catheter (Medtronic, Irvine, California, USA) used for intracranial thrombectomy have been poorly evaluated thus far. We report our preliminary results with the ARC with regard to angiographic reperfusion, duration of thrombectomy, safety, and clinical outcome at 90 days. METHODS: In a single-center series including 20 large-vessel occlusion stroke patients who were collected prospectively, we retrospectively evaluated the safety and efficacy profiles of the ARC intracranial catheter for first-line contact aspiration. Successful reperfusion was defined as modified Thrombolysis in Cerebrovascular Infarction (mTICI) scores 2b-3 at final angiogram and functional independence as modified Rankin Scale score 0-2 at 90 days. RESULTS: Median admission National Institutes of Health Stroke Scale score was 15, and previous intravenous thrombolysis was administered in 12 patients (60%). Proximal occlusion was located in the anterior circulation in 16 patients (80%). Primary aspiration alone was successful in 10 of 15 patients (67%) within a median time of 26 minutes. Overall successful reperfusion was achieved in 16 patients (80%) within a median time of 31 minutes. There were no device-related events. Median National Institutes of Health Stroke Scale score was 2.5 at discharge. Six of 17 patients (35%) were independent, and 6 (35%) died at 90 days. Symptomatic intracerebral hemorrhage occurred in 5%. CONCLUSIONS: In our initial experience, the ARC appears safe and efficient for contact aspiration thrombectomy in large-vessel stroke therapy. However, improvement of its distal navigability needs further development to improve the success of aspiration alone, and large prospective studies are warranted. PMID- 28987855 TI - Comparison of Quality Metrics for Pediatric Shunt Surgery and Proposal of the Negative Shunt Revision Rate. AB - OBJECTIVE: Shunt surgery is common in pediatric neurosurgery and is associated with relevant complication rates. We aimed to compare previously published metrics in a single data set and propose the Negative Shunt Revision Rate (NSRR), defined as proportion of shunt explorations revealing a properly working system, as a new quality metric. METHODS: Retrospective analysis of our shunt surgery activity in 2015 was performed. Demographic, clinical, and radiologic variables were extracted from electronic medical notes. Surgical Activity Rate, Revision Quotient, 30-day shunt malfunction rate, 90-day global shunt revision rate, Preventable Shunt Revision Rate, and novel NSRR were calculated. RESULTS: Of 60 shunt operations analyzed, 18 (39%) were new shunt insertions, and 42 (70%) were revisions. Median age was 18 months (range, 0.03-204 months), and main etiologies were posthemorrhagic (n = 16; 41%), congenital (n = 11; 28%), and tumor associated (n = 8; 21%) hydrocephalus. Within 90 days after index surgery, 13 shunt failures occurred, predominantly owing to proximal failure (n = 6; 46%). Surgical Activity Rate was 0.127, Revision Quotient was 2.333, 30-day shunt malfunction rate was 0.166, 90-day global shunt revision rate was 21.7%, and Preventable Shunt Revision Rate was 38.5%. NSRR was 7.1%. CONCLUSIONS: Our results correlate with published values and offer measurement of quality that can be compared across studies and considered patient-oriented, easily measurable, and potentially modifiable. We propose NSRR as a new quality metric, covering an aspect of shunt surgery that was not addressed previously. PMID- 28987856 TI - Comparison of Chronic Dysphagia in Standalone versus Conventional Plate and Cage Fusion. AB - INTRODUCTION: Standalone cages have gained popularity because of their ease of implantation, reduced operating time, and lower profile compared with traditional plate and cage systems. The aim of this study was to compare the risk of chronic dysphagia between those who undergwent anterior cervical discectomy and fusion (ACDF) with traditional plating techniques and those who underwent standalone procedures. MATERIAL AND METHODS: Between 2014 and 2015, we identified 377 consecutive patients who met the study criteria (standalone, n = 211; plate-cage, n = 166). Patient-specific characteristics and surgical characteristics were collected preoperatively. In addition, the Dysphagia Disability Index (DDI) was collected 2 years postoperatively by telephone interview. RESULTS: Among the patients who underwent a standalone procedure, 84% (n = 177) were available for their 2-year follow-up visit in comparison with 75% (n = 124) for plate-cage procedures. There was no statistically significant difference in postoperative DDI scores between the 2 groups, controlling for prior surgery and smoking. However, the strongest risk factors for higher DDI scores were prior cervical surgery (mean 6.0 points higher) and smoking (mean 6.2 points higher). Twenty seven patients (8.9%) experienced chronic dysphagia. The risk was higher in the plate-cage group (n = 15, 12.1%) than in the standalone group (n = 12, 6.7%), but this difference did not reach statistical significance. CONCLUSION: Despite similar mean DDI scores, patients who undergo anterior cervical discectomy with a plate-cage may be at a higher risk for chronic dysphagia than are those with a standalone approach, but further studies with larger sample sizes are necessary to establish this relationship with greater confidence. PMID- 28987857 TI - Intracranial Hemorrhage in Patients with Durable Mechanical Circulatory Support Devices: Institutional Review and Proposed Treatment Algorithm. AB - BACKGROUND: Spontaneous intracranial hemorrhage (ICH) is frequently managed in neurosurgery. Patients with durable mechanical circulatory support devices, including total artificial heart (TAH) and left ventricular assist device (LVAD), are often encountered in the setting of ICH. Although durable mechanical circulatory support devices have improved survival and quality of life for patients with advanced heart failure, ICH is one of the most feared complications following LVAD and TAH implantation. Owing to anticoagulation and clinically relevant acquired coagulopathies, ICH should be treated promptly by neurosurgeons and cardiac critical care providers. We provide an analysis of ICH in patients with mechanical circulatory support and propose a treatment algorithm. METHODS: We retrospectively reviewed medical records from 2013-2016 for patients with a durable mechanical circulatory device at Banner-University of Arizona Medical Center Tucson. All patients with suspected ICH underwent computed tomography scan of the brain. Anticoagulation was managed by the cardiothoracic surgeon. RESULTS: In 58 patients, an LVAD (n = 49), TAH (n = 10), or both (n = 1) were implanted. Both acquired von Willebrand disease and spontaneous ICH were diagnosed in 5 patients (8.6%) who underwent LVAD implantation. Seven neurosurgical procedures were performed in 2 patients. The overall mortality rate was 60%. Two patients had little or no deficits after treatment with modified Rankin Scale score of 1 and 2, respectively. CONCLUSIONS: We propose a novel treatment algorithm to manage patients with a LVAD or TAH and ICH, implemented in a multidisciplinary manner to best avoid neurologic and cardiovascular complications. PMID- 28987858 TI - [Effectiveness of an educational program for respiratory rehabilitation of Chronic Obstructive Pulmonary Disease patients in Primary Care in improving the quality of life, symptoms, and clinical risk]. AB - AIM: To determine the impact of an educational program to improve the management of chronic obstructive pulmonary disease (COPD) that contributes to an increase of the quality of life, exercise capacity, level of dyspnoea, and clinical risk. DESIGN: Intervention study without controls. LOCATION: Primary Healthcare Centre. PARTICIPANTS: 193 patients with COPD were invited, 73 accepted and 55 participated in the educational program. INTERVENTIONS: Respiratory rehabilitation educational program with basic concepts of pulmonary and respiratory pathophysiology, respiratory physiotherapy exercises, practical workshop on the use of the most frequent inhalation devices, understanding of chronic disease and self-care measures in case of exacerbation. MAIN MEASUREMENTS: The quality of life (the COPD assessment test), exercise tolerance (the Six-Minute Walk Test), rating of perceived exertion (Borg Dyspnoea Score) and clinical risk (BODE index) were assessed by means of validated questionnaires in Spanish. RESULTS: A total of 43 (78.2%) participants completed the program. An improvement in the quality of life by a mean of 3.3 points was observed (95%CI; 1.76-4.84). Just over half (53.5%) of the participants obtained a clinically relevant improvement. Participants also improved their physical exercise capacity at post-intervention by increasing the distance that they walked in 6min by a mean of 20.76m (95%CI; 2.57-38.95). Improvements in the level of dyspnoea and clinical risk were also observed. CONCLUSIONS: The educational program shows a statistically significant and clinically relevant improvement in the quality of life, fatigue, symptomatology, exercise capacity, level of dyspnoea, and clinical risk. The program is adaptable to the health care routine of healthcare centres. PMID- 28987859 TI - Active Surveillance or Office Fulguration for Low Grade Ta Bladder Tumors: A Win Win for Patients and Urologists. PMID- 28987860 TI - The impact of a continuing training program on the perceived improvement in quality of health care delivered by health care professionals. AB - There is abundant scientific literature concerning factors that affect patients' perceptions of the quality of health care. However, there are few published works that consider the opinions of health care professionals. This article aims to conjointly analyse two organisational strategies that determine professional health care practice: continuous training and quality of care. The objective is to examine the opinions of physicians and nurses on the improvement of the quality of care after a 'learning by doing' program. An evaluation method was designed that integrates the main variables that intervene in quality of care. An online questionnaire was utilised for collecting opinions on the effects of the training program. A total of 184 nurses and 180 other medical professionals participated in the program and all of them were asked to complete the questionnaire. A descriptive, and inferential statistical analysis was undertaken and results showed that there is a direct relationship between perceptions about: satisfaction, professional competence, training modality, optimisation of health resources and quality of care. PMID- 28987861 TI - Genome-wide transcriptome profiling of genes associated with arsenate toxicity in an arsenic-tolerant rice mutant. AB - The presence of arsenic (As) in polluted environments, such as ground water, affects the accumulation of As in rice grains and causes a serious threat to human health. However, the precise molecular regulations related to As toxicity and tolerance in rice remain largely unknown. In the present study, we developed an arsenic-tolerant type 1 (ATT1) rice mutant by gamma-irradiation mutagenesis and performed genome-wide transcriptome analysis for the characterization of As responsive genes. Toxicity inhibited transcriptional regulation of putative genes involved in photosynthesis, mitochondrial electron transport, and lipid biosynthesis metabolism in wild-type (WT) and ATT1 rice mutant. However, many cysteine biosynthesis-related genes were significantly upregulated in both plants. We also attempted to elucidate the putative genes associated with As tolerance by comparing transcriptomes and identified ATT1-specific transcriptional regulation of genes involved in stress and RNA-protein synthesis. This analysis identified 50 genes that had DNA polymorphisms in upstream regions that differed from those in the exon regions, which suggested that genetic variations in the upstream regions might enhance As tolerance in the mutants. Therefore, the expression profiles of the genes evaluated in this study may improve understanding of the functional roles of As-related genes in response to As tolerance mechanisms and could potentially be used in molecular breeding to limit As accumulation in rice grains. PMID- 28987862 TI - Overexpressing sweetpotato peroxidase gene swpa4 affects nitric oxide production by activating the expression of reactive oxygen species- and nitric oxide-related genes in tobacco. AB - Reactive oxygen species (ROS) and nitric oxide (NO) are key signaling molecules involved in various developmental and stress responses in plants. NO and ROS production, which is triggered by various stimuli, activates downstream signaling pathways to help plants cope with abiotic and biotic stresses. Recent evidence suggests that the interplay between NO and ROS signaling plays a critical role in regulating stress responses. However, the underlying molecular mechanism remains poorly understood. We previously reported that transgenic tobacco overexpressing the swpa4 peroxidase (POD) gene from sweetpotato exhibits increased tolerance to stress. Overexpression of swpa4 also induces the generation of H2O2 and activates the expression of various extracellular acidic pathogenesis-related (PR) genes. Here, we show that swpa4 positively regulates the expression of ROS- and NO related genes in transgenic tobacco plants. Plants expressing swpa4 exhibited increased expression of ROS-related genes and increased ROS-related enzyme activity under normal conditions and H2O2 treatment, whereas the expression of NO associated 1 (NOA1) only increased under normal conditions. Moreover, plants overexpressing swpa4 showed increased NO levels under normal conditions and after treatment with the NO donor sodium nitroprusside (SNP). Interestingly, treatment with a POD inhibitor dramatically reduced NO levels in swpa4 transgenic plants. These findings suggest that swpa4 regulates H2O2 and NO homeostasis in plants under stress conditions, thereby establishing a possible molecular link between the NO and ROS signaling pathways. PMID- 28987863 TI - Six NAC transcription factors involved in response to TYLCV infection in resistant and susceptible tomato cultivars. AB - NAC transcription factors (TFs) belong to plant-specific TFs, which have been identified in many plant species. The NAC TFs act as the nodes of a regulatory network in plant's response to abiotic and biotic stresses. Till now, response of tomato NAC TFs involved in Tomato yellow leaf curl virus (TYLCV) infection is unknown. In the present study, six NAC TFs were identified to respond to TYLCV infection in tomato. We observed that transcripts of four NAC genes (SlNAC20, SlNAC24, SlNAC47, and SlNAC61) were induced after TYLCV infection in resistant tomato cultivar. Virus-induced gene silencing analysis (VIGS) indicated that SlNAC61 played positive roles in response to TYLCV infection. Tomato NAC TFs were not only involved in defense regulation but in development and stress progress. These NAC TFs interacted with other proteins, including protein phosphatase and mitogen-activated protein kinase. Some defense response TFs, such as WRKY, TGA, MYB, NAC, could interact with NAC proteins by binding cis-elements in promoter regions of NAC TFs. These identified tomato NAC TFs cooperated with other TFs and proteins, indicating the complex response mechanism of described NAC TFs involved in TYLCV infection. The results will offer new evidence to further understand the NAC TFs involved in response to TYLCV infection in tomato. PMID- 28987864 TI - Food stories: Unraveling the mechanisms underlying healthful eating. AB - The biomedical model of health (BMH) studies the causes and origins of disease. When applied to nutrition research, eating is studied as a behavior that supports physical health. However, the lack of attention the BMH pays to social and historical circumstances in which health behaviors are constructed has been widely addressed in literature. When people are studied without considering contextual influences, the relevance to everyday life is limited. As a result, how individuals actively deal with their context to manage healthful eating is poorly understood. This research applies a complementary model, salutogenic model of health (SMH), and uses life course research methodology to study a group of healthy eaters. The purpose of this research is to unravel how healthful eating develops in everyday life. Healthy eaters (n = 17) were identified and recruited from the NQplus research panel at Wageningen University, the Netherlands. Life course experiences were examined through narrative inquiry. Participants recalled and visually explored life experiences with food and health using timelines. Results indicate that healthful eating results from exposure to individual- and context-bounded factors during childhood and adulthood and involves specific mental and social capacities relevant to coping including amongst others, critical self-awareness; flexibility, craftiness, and fortitude. Through life course learning moments, participants were able to develop proactive coping strategies which strengthened their sense of agency and helped them in overcoming stressors and challenges. Findings show that nutrition strategies should not only focus on strengthening food-specific factors like cooking skills and nutrition knowledge, but other factors like stress management, empowerment, and participation. Such factors support the development of adaptive skills and behaviors, enable individuals to deal with the demands of everyday life, and are building blocks for health promotion. PMID- 28987865 TI - Hyaluronan synthase 3 promotes plaque inflammation and atheroprogression. AB - OBJECTIVE: Hyaluronan (HA) is a prominent component of the provisional extracellular matrix (ECM) present in the neointima of atherosclerotic plaques. Here the role of HA synthase 3 (HAS3) in atheroprogression was studied. APPROACH AND RESULTS: It is demonstrated here that HAS isoenzymes 1, -2 and -3 are expressed in human atherosclerotic plaques of the carotid artery. In Apolipoprotein E (Apoe)-deficient mice Has3 expression is increased early during lesion formation when macrophages enter atherosclerotic plaques. Importantly, HAS3 expression in vascular smooth muscle cells (VSMC) was found to be regulated by interleukin 1 beta (IL-1beta) in an NFkB dependent manner and blocking antibodies to IL-1beta abrogate Has3 expression in VSMC by activated macrophages. Has3/Apoe double deficient mice developed less atherosclerosis characterized by decreased Th1-cell responses, decreased IL-12 release, and decreased macrophage driven inflammation. CONCLUSIONS: Inhibition of HAS3-dependent synthesis of HA dampens systemic Th1 cell polarization and reduces plaque inflammation. These data suggest that HAS3 might be a promising therapeutic target in atherosclerosis. Moreover, because HAS3 is regulated by IL-1beta, our results suggest that therapeutic anti-IL-1beta antibodies, recently tested in human clinical trials (CANTOS), may exert their beneficial effects on inflammation in post-myocardial infarction patients in part via effects on HAS3. TOC categorybasic study TOC subcategoryarteriosclerosis. PMID- 28987866 TI - Kinematic patterns in normal and degenerative shoulders. Part II: Review of 3-D scapular kinematic patterns in patients with shoulder pain, and clinical implications. AB - BACKGROUND: The global range of motion of the arm is the result of a coordinated motion of the shoulder complex including glenohumeral (GH), scapulothoracic, sternoclavicular and acromioclavicular joints. METHODS: This study is a non systematic review of kinematic patterns in degenerated shoulders. It is a based on our own research on the kinematics of the shoulder complex and clinical experience. RESULTS: For patients with subacromial impingement syndrome without rotator-cuff tears, most kinematic studies showed a small superior humeral translation relative to the glenoid and decreased scapular lateral rotation and posterior tilt. These scapular kinematic modifications could decrease the subacromial space and favor rotator-cuff tendon injury. For patients with shoulder pain and restricted mobility, the studies showed a significant increase in scapular lateral rotation generally seen as a compensation mechanism of GH decreased range of motion. For patients with multidirectional GH instability, the studies found an antero-inferior decentering of the humeral head, decreased scapular lateral rotation and increased scapular internal rotation. CONCLUSION: The clinical or instrumented assessment of the shoulder complex with a degenerative pathology must include the analysis of scapula-clavicle and trunk movements complementing the GH assessment. Depending on the individual clinical case, scapular dyskinesis could be the cause or the consequence of the shoulder degenerative pathology. For most degenerative shoulder pathologies, the rehabilitation program should take into account the whole shoulder complex and include first a scapular and trunk postural-correcting strategy, then scapulothoracic muscle rehabilitation (especially serratus anterior and trapezius inferior and medium parts) and finally neuromotor techniques to recover appropriate upper-limb kinematic schemas for daily and/or sports activities. PMID- 28987867 TI - Neuroprotective effect of a new variant of Epo nonhematopoietic against oxidative stress. AB - Human erythropoietin is mainly recognized for its hematopoietic function; however, by binding to its receptor (EpoR), it can activate different signaling pathways as STAT, PI3K, MAPK and RAS to increase cellular differentiation or provide neuroprotective effects, among others. A recombinant human erythropoietin variant with low glycosylation and without hematopoietic effect (EpoL) was purified from skimmed goat milk. Recombinant human erythropoietin (Epo) was obtained from CHO cell line and used as control to compare EpoL effects. Neuroprotection studies were performed in PC12 cells and rat hippocampal slices. Cells were pretreated during 1h with EpoL or Epo and exposed to oxidative agents (H2O2 or FCCP); cell viability was assayed at the end of the experiment by the MTT method. Hippocampal slices were exposed to 15min of oxygen and glucose deprivation (OGD) and the neuroprotective drugs EpoL or Epo were incubated for 2h post-OGD in re-oxygenated medium. Cell cultures stressed with oxidative agents, and pretreated with EpoL, showed neuroprotective effects of 30% at a concentration 10 times lower than that of Epo. Moreover, similar differences were observed in OGD ex vivo assays. Neuroprotection elicited by EpoL was lost when an antibody against EpoR was present, indicating that its effect is EpoR-dependent. In conclusion, our results suggest that EpoL has a more potent neuroprotective profile than Epo against oxidative stress, mediated by activation of EpoR, thus EpoL represents an important target to develop a potential biopharmaceutical to treat different central nervous system pathologies related to oxidative stress such as stroke or neurodegenerative diseases. PMID- 28987869 TI - Sources of 137Cs to an Arctic fjord (Hornsund, Svalbard). AB - Although primary sources of anthropogenic 137Cs have decreased nowadays, the Arctic is exposed to a variety of secondary sources. These include riverine run off, oceanic currents, drifting sea ice, melting glaciers and permafrost. Recent reports underline the role of glaciers, specifically cryoconite holes, in radionuclide accumulation. Therefore, this study investigates the hypothesis that melting glaciers are an important means of delivering 137Cs for Arctic fjord (Hornsund, Svalbard). As marine sediments are the final sink for most contaminants, seven 30-40 cm long sediment cores collected in 2016 were investigated for 137Cs activity concentration. Five were collected in a transect from the central to the outer part of the fjord while two were collected within one km of the different melting tidewater glaciers. Sediment layers were dated using 210Pb to reveal the history of 137Cs accumulation. The measured 137Cs activity concentrations ranged from <0.1 to 7.7 Bq kg-1. The activity concentrations ranging from 0.3 to 3.1 Bq kg-1 were measured in surface (0-2 cm) sediments. The total 137Cs inventories were calculated for five station and ranged from 322 to 908 Bq m-2, of which 29-34 Bq m-2 were deposited within the last decade. At two stations characterized by largest sediment accumulation rates only the last decade inventories were calculated and they ranged from 13 to 444 Bq.m-2. The mean of 137Cs fluxes calculated for last decade ranged from 2.7 to 44.1 Bq m-2yr-1. The history of 137Cs environmental inputs was well revealed in the sediments as the 137Cs penetration depth agreed with the time of its introduction to the Arctic and the most pronounced 137Cs activity concentration peak was found in sediments dated for circa 1963. Although 137Cs fluxes and inventories were largest in the glacial bay (Brepollen), the 137Cs was diluted in a large amount of sedimenting material. Based on the results in this study, the glaciers do not appear to act as important sources of 137Cs to the marine environment in the Hornsund fjord. PMID- 28987870 TI - The critical size of focal articular cartilage defects is associated with strains in the collagen fibers. AB - The size of full-thickness focal cartilage defect is accepted to be predictive of its fate, but at which size threshold treatment is required is unclear. Clarification of the mechanism behind this threshold effect will help determining when treatment is required. The objective was to investigate the effect of defect size on strains in the collagen fibers and the non-fibrillar matrix of surrounding cartilage. These strains may indicate matrix disruption. Tissue deformation into the defect was expected, stretching adjacent superficial collagen fibers, while an osteochondral implant was expected to prevent these deformations. Finite element simulations of cartilage/cartilage contact for intact, 0.5 to 8mm wide defects and 8mm implant cases were performed. Impact, a load increase to 2MPa in 1ms, and creep loading, a constant load of 0.5MPa for 900s, scenarios were simulated. A composition-based material model for articular cartilage was employed. Impact loading caused low strain levels for all models. Creep loading increased deviatoric strains and collagen strains in the surrounding cartilage. Deviatoric strains increased gradually with defect size, but the surface area at which collagen fiber strains exceeded failure thresholds, abruptly increased for small increases of defect size. This was caused by a narrow distribution of collagen fiber strains resulting from the non-linear stiffness of the fibers. We postulate this might be the mechanism behind the existence of a critical defect size. Filling of the defect with an implant reduced deviatoric and collagen fiber strains towards values for intact cartilage. PMID- 28987868 TI - Impairment of Akt activity by CYP2E1 mediated oxidative stress is involved in chronic ethanol-induced fatty liver. AB - Protein kinase B (PKB/Akt) plays important roles in the regulation of lipid homeostasis, and impairment of Akt activity has been demonstrated to be involved in the development of non-alcoholic fatty liver disease (NAFLD). Previous studies suggest that cytochrome P4502E1 (CYP2E1) plays causal roles in the pathogenesis of alcoholic fatty liver (AFL). We hypothesized that Akt activity might be impaired due to CYP2E1-induced oxidative stress in chronic ethanol-induced hepatic steatosis. In this study, we found that chronic ethanol-induced hepatic steatosis was accompanied with reduced phosphorylation of Akt at Thr308 in mice liver. Chronic ethanol exposure had no effects on the protein levels of phosphatidylinositol 3 kinase (PI3K) and phosphatase and tensin homologue deleted on chromosome ten (PTEN), and led to a slight decrease of phosphoinositide dependent protein kinase 1 (PDK-1) protein level. Ethanol exposure resulted in increased levels of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE)-Akt adducts, which was significantly inhibited by chlormethiazole (CMZ), an efficient CYP2E1 inhibitor. Interestingly, N-acetyl-L-cysteine (NAC) significantly attenuated chronic ethanol-induced hepatic fat accumulation and the decline of Akt phosphorylation at Thr308. In the in vitro studies, Akt phosphorylation was suppressed in CYP2E1-expressing HepG2 (CYP2E1-HepG2) cells compared with the negative control HepG2 (NC-HepG2) cells, and 4-HNE treatment led to significant decrease of Akt phosphorylation at Thr308 in wild type HepG2 cells. Lastly, pharmacological activation of Akt by insulin-like growth factor-1 (IGF-1) significantly alleviated chronic ethanol-induced fatty liver in mice. Collectively, these results indicate that CYP2E1-induced oxidative stress may be responsible for ethanol-induced suppression of Akt phosphorylation and pharmacological modulation of Akt in liver may be an effective strategy for the treatment of ethanol-induced fatty liver. PMID- 28987871 TI - Quantification of gravity-induced skin strain across the breast surface. AB - BACKGROUND: Quantification of the magnitude of skin strain in different regions of the breast may help to estimate possible gravity-induced damage whilst also being able to inform the selection of incision locations during breast surgery. The aim of this study was to quantify static skin strain over the breast surface and to estimate the risk of skin damage caused by gravitational loading. METHODS: Fourteen participants had 21 markers applied to their torso and left breast. The non-gravity breast position was estimated as the mid-point of the breast positions in water and soybean oil (higher and lower density than breast respectively). The static gravity-loaded breast position was also measured. Skin strain was calculated as the percentage extension between adjacent breast markers in the gravity and non-gravity loaded conditions. FINDINGS: Gravity induced breast deformation caused peak strains ranging from 14 to 75% across participants, with potentially damaging skin strain (>60%) in one participant and skin strains above 30% (skin resistance zone) in a further four participants. These peak strain values all occurred in the longitudinal direction in the upper region of the breast skin. In the latitudinal direction, smaller-breasted participants experienced greater strain on the outer (lateral) breast regions and less strain on the inner (medial) breast regions, a trend which was reversed in the larger breasted participants (above size 34D). INTERPRETATION: To reduce tension on surgical incisions it is suggested that preference should be given to medial latitudinal locations for smaller breasted women and lateral latitudinal locations for larger breasted women. PMID- 28987872 TI - Gender difference of shoulder-pelvic kinematic integration for trunk rotation directions in healthy older adults. AB - BACKGROUND: The trunk coordination pattern has been extensively studied, and there is a higher pain prevalence and asymmetry in female older adults. However, there is a lack of investigation of different directions of trunk rotation and asymmetrical compensatory strategies of motor control between genders. The purpose of this study was to investigate shoulder and pelvic ranges of motion (ROM) as well as relative phases (RP) for the different directions of trunk rotation between genders in healthy older adults. METHODS: There were 62 right hand dominant older adults in this study (31 female subjects (68.4 [5.62]years) and 31 male subjects (68.7 [5.68]years)). The participants performed trunk axial rotation from the left to the right direction (RP1) and then returned to the left side (RP2), three times repeatedly in standing. The measurements included shoulder and pelvic ROM, RP1, and RP2. The RP was defined as the average absolute relative phase, which was the difference between the phase angle of the shoulder and the phase angle of the pelvis during trunk rotation. FINDINGS: The female group demonstrated significantly greater pelvic rotation compared to the male group (98.64 [24.67] vs. 86.96 [18.97]; t=2.09, p=0.04) during trunk rotation. The pelvic ROM demonstrated a significant positive correlation with shoulder ROM in both genders; however, the RP was negatively correlated with the pelvis. For pelvic rotation, the male group demonstrated a negative correlation with RP1 (r= 0.68, p<0.01) and RP2 (r=-0.60, p<0.01) while the female group demonstrated a negative correlation with RP2 (r=-0.53, p<0.01). The ageing factor demonstrated negative correlations with ROM for the shoulder and pelvis in both genders. INTERPRETATION: Although no gender difference was indicated on the direction of RP, the pelvic ROM was significantly lesser in the male group. The male group demonstrated lesser pelvic rotation in both directions of rotation; however, the female group showed lesser pelvic rotation in RP2. The male group demonstrated stiffened pelvic rotation and greater shoulder rotation in both directions while the female group demonstrated pelvic stiffness only in the direction from right to left rotation. Clinicians need to consider this directional asymmetry of trunk rotation to enhance integrated shoulder-pelvic coordination in female older adults. MINI ABSTRACT: A coordinative pattern of different directions of trunk rotation was investigated in healthy older adults. The pelvic range of motion was lesser in the male group compared with the female group. The female group demonstrated pelvic stiffness only in the direction from right to left rotation, while the male group demonstrated pelvic stiffness in both directions. Clinicians need to understand the gender difference of directional coordination as integrated coordination in female older adults. PMID- 28987874 TI - Quantifying the in vivo quasi-static response to loading of sub-dermal tissues in the human buttock using magnetic resonance imaging. AB - BACKGROUND: The design of seating systems to improve comfort and reduce injury would benefit from improved understanding of the deformation and strain patterns in soft tissues, particularly in the gluteal region. METHODS: Ten healthy men were positioned in a semi-recumbent posture while their pelvic and thigh region was scanned using a wide-bore magnetic resonance imaging (MRI) scanner. Independent measurements of deformation for muscles and fat were taken for the transition from non-weight-bearing to weight-bearing loads in three stages. A weight-bearing load was achieved through having the subject supported by a flat, rigid surface. A non-weight-bearing condition was achieved by removing the support under the left buttock, leaving all soft tissue layers undeformed. An intermediate condition partially relieved the subject's left buttock by lowering the support relative to the pelvis by 20mm, which left the buttock partially deformed. For each of these conditions, the thicknesses of muscle and fat tissues below the ischial tuberosity and the greater trochanter were measured from the MRI data. FINDINGS: In this dataset, the greatest soft tissue deformation took place below the ischial tuberosity, with muscles (mean=17.7mm, SD=4.8mm) deforming more than fat tissues (mean=4.3mm, SD=5.6mm). Muscles deformed through both steps of the transition from weight-bearing to non-weight-bearing conditions, while subcutaneous fat deformed little after the first transition from non-weight-bearing to partial-weight-bearing. High inter-subject variability in muscle and fat tissue strains was observed. INTERPRETATION: Our findings highlight the importance of considering inter-subject variability when designing seating systems. PMID- 28987873 TI - Hip joint biomechanics in those with and without post-traumatic knee osteoarthritis after anterior cruciate ligament injury. AB - BACKGROUND: Anterior cruciate ligament injury results in altered kinematics and kinetics in the knee and hip joints that persist despite surgical reconstruction and rehabilitation. Abnormal movement patterns and a history of osteoarthritis are risk factors for articular cartilage degeneration in additional joints. The purpose of this study was to determine if hip joint biomechanics early after anterior cruciate ligament injury and reconstruction differ between patients with and without post-traumatic knee osteoarthritis 5years after reconstruction. The study's rationale was that individuals who develop knee osteoarthritis after anterior cruciate ligament injury may also demonstrate large alterations in hip joint biomechanics. METHODS: Nineteen athletes with anterior cruciate ligament injury completed standard gait analysis before (baseline) and after (post training) extended pre-operative rehabilitation and at 6months, 1year, and 2years after reconstruction. Weightbearing knee radiographs were completed 5years after reconstruction to identify medial compartment osteoarthritis. FINDINGS: Five of 19 patients had knee osteoarthritis at 5years after anterior cruciate ligament reconstruction. Patients with knee osteoarthritis at 5years walked with smaller sagittal plane hip angles (P: 0.043) and lower sagittal (P: 0.021) and frontal plane (P: 0.042) external hip moments in the injured limb before and after reconstruction compared to those without knee osteoarthritis. INTERPRETATION: The current findings suggest hip joint biomechanics may be altered in patients who develop post-traumatic knee osteoarthritis. Further study is needed to confirm whether the risk of non-traumatic hip pathology is increased after anterior cruciate ligament injury and if hip joint biomechanics influence its development. PMID- 28987876 TI - Synthesis and cholinesterase inhibitory activity study of new piperidone grafted spiropyrrolidines. AB - Alzheimer's disease (AD) is a prevalent neurodegenerative disorder, which affected 35 million people in the world. The most practiced approach to improve the life expectancy of AD patients is to increase acetylcholine neurotransmitter level at cholinergic synapses by inhibition of cholinesterase enzymes. A series of unreported piperidone grafted spiropyrrolidines 8(a-p) were synthesized and evaluated in vitro for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities. Therein, compounds 8h and 8l displayed more potent AChE enzyme inhibition than standard drug with IC50 values of 1.88 and 1.37 uM, respectively. Molecular docking simulations for 8l possessing the most potent AChE inhibitory activities, disclosed its interesting binding templates to the active site channel of AChE enzymes. These compounds are remarkable AChE inhibitors and have potential as AD drugs. PMID- 28987875 TI - Activation of IGF-1 receptors and Akt signaling by systemic hyperinsulinemia contributes to cardiac hypertrophy but does not regulate cardiac autophagy in obese diabetic mice. AB - Autophagy plays an important role in the maintenance of normal heart function. However, the role of autophagy in the inulin resistant and diabetic heart is not well understood. Furthermore, the upstream signaling and the downstream targets involved in cardiac autophagy regulation during obesity and type 2 diabetes mellitus (T2DM) are not fully elucidated. The aim of this study was to measure autophagic flux and to dissect the upstream and downstream signaling involved in cardiac autophagy regulation in the hearts of obese T2DM mice. Our study demonstrated that cardiac autophagic flux is suppressed in the heart of obese diabetic (ob/ob) mice due to impaired autophagosome formation. We showed that suppression of autophagy was due to sustained activation of mTOR as we could restore cardiac autophagy by inhibiting mTOR. Moreover, the novel finding of this study is that while IGF-1 receptor-mediated Akt activation contributes to cardiac hypertrophy, it is not involved in mTOR activation and autophagy suppression in obesity and T2DM. In contrast, inhibition of ERK signaling abolished mTOR activation and restored autophagy in the heart of obese diabetic (ob/ob) mice. The study identifies mechanisms regulating cardiac autophagy in obesity and T2DM that are mediated by ERK/mTOR but are distinct from Akt. The findings are of significant importance as they demonstrate for the first time the contribution of IGF-1 receptors (IGF-1R) and Akt signaling in cardiac hypertrophy but not in cardiac autophagy regulation in obesity and T2DM. PMID- 28987877 TI - The anthraquinone emodin inhibits the non-exported FIKK kinase from Plasmodium falciparum. AB - The FIKK family of kinases is unique to parasites of the Apicomplexan order, which includes all malaria parasites. Plasmodium falciparum, the most virulent form of human malaria, has a family of 19 FIKK kinases, most of which are exported into the host red blood cell during malaria infection. Here, we confirm that FIKK 8 is a non-exported member of the FIKK kinase family. Through expression and purification of the recombinant kinase domain, we establish that emodin is a relatively high-affinity (IC50=2MUM) inhibitor of PfFk8. Closely related anthraquinones do not inhibit PfFk8, suggesting that the particular substitution pattern of emodin is critical to the inhibitory pharmacophore. This first report of a P. falciparum FIKK kinase inhibitor lays the groundwork for developing specific inhibitors of the various members of the FIKK kinase family in order to probe their physiological function. PMID- 28987878 TI - Co-delivery of nucleoside-modified mRNA and TLR agonists for cancer immunotherapy: Restoring the immunogenicity of immunosilent mRNA. AB - This study reports on the design of mRNA and adjuvant-loaded lipid nanoparticles for therapeutic cancer vaccination. The use of nucleoside-modified mRNA has previously been shown to improve the translational capacity and safety of mRNA therapeutics, as it prevents the induction of type I interferons (IFNs). However, type I IFNs were identified as the key molecules that trigger the activation of antigen presenting cells, and as such drive T cell immunity. We demonstrate that nucleoside-modified mRNA can be co-delivered with the clinically approved TLR agonist monophosphoryl lipid A (MPLA). As such, we simultaneously allow high antigen expression in vivo while substituting the type I IFN response by a more controllable adjuvant. This strategy shows promise to induce effective antigen specific T cell immunity and may be useful to enhance the safety of mRNA vaccines. PMID- 28987879 TI - Thioaptamer targeted discoidal microparticles increase self immunity and reduce Mycobacterium tuberculosis burden in mice. AB - Worldwide, tuberculosis (TB) remains one of the most prevalent infectious diseases causing morbidity and death in >1.5 million patients annually. Mycobacterium tuberculosis (Mtb), the etiologic agent of TB, usually resides in the alveolar macrophages. Current tuberculosis treatment methods require more than six months, and low compliance often leads to therapeutic failure and multidrug resistant strain development. Critical to improving TB-therapy is shortening treatment duration and increasing therapeutic efficacy. In this study, we sought to determine if lung hemodynamics and pathological changes in Mtb infected cells can be used for the selective targeting of microparticles to infected tissue(s). Thioaptamers (TA) with CD44 (CD44TA) targeting moiety were conjugated to discoidal silicon mesoporous microparticles (SMP) to enhance accumulation of these agents/carriers in the infected macrophages in the lungs. In vitro, CD44TA-SMP accumulated in macrophages infected with mycobacteria efficiently killing the infected cells and decreasing survival of mycobacteria. In vivo, increased accumulations of CD44TA-SMP were recorded in the lung of M. tuberculosis infected mice as compared to controls. TA-targeted carriers significantly diminished bacterial load in the lungs and caused recruitment of T lymphocytes. Proposed mechanism of action of the designed vector accounts for a combination of increased uptake of particles that leads to infected macrophage death, as well as, activation of cellular immunity by the TA, causing increased T cell accumulation in the treated lungs. Based on our data with CD44TA-SMP, we anticipate that this drug carrier can open new avenues in TB management. PMID- 28987880 TI - Heparin-functionalized polymer graft surface eluting MK2 inhibitory peptide to improve hemocompatibility and anti-neointimal activity. AB - The leading cause of synthetic graft failure includes thrombotic occlusion and intimal hyperplasia at the site of vascular anastomosis. Herein, we report a co immobilization strategy of heparin and potent anti-neointimal drug (Mitogen Activated Protein Kinase II inhibitory peptide; MK2i) by using a tyrosinase catalyzed oxidative reaction for preventing thrombotic occlusion and neointimal formation of synthetic vascular grafts. The binding of heparin-tyramine polymer (HT) onto the polycarprolactone (PCL) surface enhanced blood compatibility with significantly reduced protein absorption (64.7% decrease) and platelet adhesion (85.6% decrease) compared to bare PCL surface. When loading MK2i, 1) the HT depot surface gained high MK2i-loading efficiency through charge-charge interaction, and 2) this depot platform enabled long-term, controlled release over 4weeks (92 272MUg/mL of MK2i). The released MK2i showed significant inhibitory effects on VSMC migration through down-regulated phosphorylation of target proteins (HSP27 and CREB) associated with intimal hyperplasia. In addition, it was found that the released MK2i infiltrated into the tissue with a cumulative manner in ex vivo human saphenous vein (HSV) model. This present study demonstrates that enzymatically HT-coated surface modification is an effective strategy to induce long-term MK2i release as well as hemocompatibility, thereby improving anti neointimal activity of synthetic vascular grafts. PMID- 28987881 TI - High-density lipoprotein mutant eye drops for the treatment of posterior eye diseases. AB - Age-related macular degeneration (AMD), in which choroidal neovascularization (CNV) affects the center of the retina (macula), leads to the irreversible visual loss. The intravitreal injection of anti-angiogenesis antibodies improved the prognosis of AMD, but relatively less invasive therapies should be explored. In the present study, we show that a high-density lipoprotein (HDL) mutant is a therapeutically active drug carrier capable of treating a posterior eye disease in mice via instillation. Various HDL mutants were prepared with apoA-I proteins fused with different cell-penetrating peptides (CPPs) and phospholipids with different alkyl chain lengths; their sizes were further controlled in the range of 10-25nm. They were screened based on the efficiency of fluorescent dye delivery to the inner retinal layer in mice. The best mutant was found to have penetratin (PEN) as a CPP, 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), and a size of 15nm. In preclinical studies on a laser-induced CNV murine model, 1week of instillation of the best mutant carrying the anti-angiogenesis drug pazopanib had dramatic therapeutic effects in reducing the CNV size. Importantly, the HDL mutant by itself contributed to the therapeutic effects. Future clinical trials for treating AMD with instillation of the HDL mutant are expected. PMID- 28987883 TI - GalNAc bio-functionalization of nanoparticles assembled by electrostatic interactions improves siRNA targeting to the liver. AB - RNA interference (RNAi) has the potential to reversibly silence any gene with high efficiency and specificity. To fulfill the clinical potential of RNAi, delivery vehicles are required to transport the short interfering RNA (siRNA) to the site of action in the cells of target tissues. Here, we describe the features of novel liver-targeted siRNA nanoparticles (NPs), co-assembled due to the complexation of alginate sulfate (AlgS) with siRNA, mediated by calcium ions bridges (AlgS-Ca2+-siRNA NPs) and then bioconjugation of a targeting ligand onto the AlgS upon the NP surface. To gain insight into the complexation process and confirm AlgS accessibility on NP surface, we investigated different schemes for fabrication. All resulting NPs, independently of the component addition order, were of average size of 130-150nm, had surface charge of <-10mV, exhibited a similar atomic composition on their surface, were efficiently uptaken by HepG2 cells and induced approx. ~90% silencing of STAT3 gene. Ca2+ and AlgS concentrations in NPs affected cell uptake and gene silencing. Bioconjugation of N-acetylgalactosamine (GalNAc), a ligand to the asialoglycoprotein receptor (ASGPR) overexpressed on hepatocytes, was validated by XPS analysis and cell uptake by receptor-mediated mechanism. After intravenous (i.v.) injection to BALB/c mice, GalNAc-NPs were targeted to liver by a factor of ~3 with lesser renal clearance compared to non-targeted NPs. We foresee that the combined advantages of site-specific targeting and reversibility of the tri-component NPs as well as the simplicity of their fabrication make them an attractive system for targeted delivery of siRNA. PMID- 28987882 TI - Radiation-enhanced delivery of systemically administered amphiphilic-CpG oligodeoxynucleotide. AB - Along with vaccines and checkpoint blockade, immune adjuvants may have an important role in tumor immunotherapy. Oligodeoxynucleotides containing unmethylated cytidyl guanosyl dinucleotide motifs (CpG ODN) are TLR9 ligands with attractive immunostimulatory properties, but intratumoral administration has been required to induce an effective anti-tumor immune response. Following on recent studies with radiation-targeted delivery of nanoparticles, we examined enhanced tumor-specific delivery of amphiphile-CpG, an albumin-binding analog of CpG ODN, following systemic administration 3days after tumor irradiation. The combination of radiation and CpG displayed superior tumor control over either treatment alone. Intravital imaging of fluorescently labeled amphiphilic-CpG revealed increased accumulation in irradiated tumors along with decreased off-target accumulation in visceral organs. Within 48h after amphiphile-CpG administration, immune activation could be detected by increased Granzyme B and Interferon gamma activity in the tumor as well as in circulating monocytes and activated CD8+ T cells. Using radiotherapy to enhance the targeting of CpG to tumors may help advance this once promising therapy to clinical relevance. PMID- 28987884 TI - Co-delivery of autophagy inhibitor ATG7 siRNA and docetaxel for breast cancer treatment. AB - The lysosomal degradation pathway of autophagy has a crucial role in protecting cancer cells from multiple endogenous and exogenous stresses, particularly during the pathogenesis of cancer. Accordingly, agents that inhibit autophagy may have broad therapeutic applications. We have developed a novel strategy based on co delivery of an autophagy related 7 (ATG7) siRNA and docetaxel (DTX) in a crosslinked, reducible, peptide-based micellar system for breast cancer treatment. Our results show that DTX and siATG7 co-treatment exhibited 2.5- and 1.7-fold higher cytotoxicity and apoptosis, respectively, in MCF-7 cells than DTX treatment alone did, which demonstrates that siATG7 enhances the efficacy and apoptotic effect of DTX. Our study showed that breast cancer cell lines differ greatly in their dependency on autophagy under conditions of normal or stress. Furthermore, siATG7 delivery in a micellar system can effectively silence the ATG7 gene, suppress DTX-induced autophagy, and exhibit improved anticancer effects. In addition, DTX in a co-delivery system showed at least a 1.84-fold greater tumor inhibition compared to that of DTX-loaded micelles in vivo. Finally, a Cy5 indicator that was loaded into crosslinked micelles revealed a remarkably high accumulation in tumors, demonstrating excellent tumor targeting ability of the micellar system. Therefore, our research demonstrated the synergistic efficacy of the combination of autophagy inhibition and chemotherapy delivered by polypeptide micelles for breast cancer therapy. PMID- 28987885 TI - Fractional order implementation of Integral Resonant Control - A nanopositioning application. AB - By exploiting the co-located sensor-actuator arrangement in typical flexure-based piezoelectric stack actuated nanopositioners, the polezero interlacing exhibited by their axial frequency response can be transformed to a zero-pole interlacing by adding a constant feed-through term. The Integral Resonant Control (IRC) utilizes this unique property to add substantial damping to the dominant resonant mode by the use of a simple integrator implemented in closed loop. IRC used in conjunction with an integral tracking scheme, effectively reduces positioning errors introduced by modelling inaccuracies or parameter uncertainties. Over the past few years, successful application of the IRC control technique to nanopositioning systems has demonstrated performance robustness, easy tunability and versatility. The main drawback has been the relatively small positioning bandwidth achievable. This paper proposes a fractional order implementation of the classical integral tracking scheme employed in tandem with the IRC scheme to deliver damping and tracking. The fractional order integrator introduces an additional design parameter which allows desired pole-placement, resulting in superior closed loop bandwidth. Simulations and experimental results are presented to validate the theory. A 250% improvement in the achievable positioning bandwidth is observed with proposed fractional order scheme. PMID- 28987886 TI - The pH of the Apoplast: Dynamic Factor with Functional Impact Under Stress. AB - The apoplast is an interconnected compartment with a thin water-film that alkalinizes under stress. This systemic pH increase may be a secondary effect without functional implications, arising from ion movements or proton-pump regulations. On the other hand, there are increasing indications that it is part of a mechanism to withstand stress. Regardless of this controversy, alkalinization of the apoplast has received little attention. The apoplastic pH (pHapo) increases not only during plant-pathogen interactions but also in response to salinity or drought. Not much is known about the mechanisms that cause the leaf apoplast to alkalinize, nor whether, and if so, how functional impact is conveyed. Controversial explanations have been given, and the unusual complexity of pHapo regulation is considered as the primary reason behind this lack of knowledge. A gathering of scattered information revealed that changes in pHapo convey functionality by regulating stomatal aperture via the effects exerted on abscisic acid. Moreover, apoplastic alkalinization may regulate growth under stress, whereas this needs to be verified. In this review, a comprehensive survey about several physiological mechanisms that alkalize the apoplast under stress is given, and the suitability of apoplastic alkalinization as transducing element for the transmission of sensory information is discussed. PMID- 28987887 TI - Glossy15 Plays an Important Role in the Divergence of the Vegetative Transition between Maize and Its Progenitor, Teosinte. PMID- 28987888 TI - Fetal death following idarubicin treatment for acute promyelocytic leukemia in pregnancy-A case report. PMID- 28987889 TI - Hormonal therapeutic strategy on the induction of accessory corpora lutea in relation to follicle size and on the increase of progesterone in sheep. AB - We determined the effect of GnRH or hCG treatment on day 4 post-time artificial insemination (FTAI) on the formation of accessory corpora lutea (acc-CL) and on the concentration of serum progesterone (P4) in sheep. Multiparous adult Merino ewes (n = 36) were synchronized for estrus using double injection of PGF2alpha agonist (125 MUg Cloprostenol) with an interval of 14 days. At 53-56 h after the second PG application, FTAI was performed. On day 4 post FTAI, ewes were either treated with analogue of GnRH (4 MUg buserelin; n = 12) or hCG (300 IU, hCG; n = 12) or saline solution (1 ml; Control; n = 12). Two laparoscopic ovarian examinations were performed on days 4 and 10 post FTAI. In the first observation, we determined the number of post ovulation corpora lutea (po-CL) and the site, number and diameter of follicles present in both ovaries. In the second laparoscopy, we observed the number of po-CL and acc-CL. The sizes of the follicles that generated the acc-CL were determined according to the position of the follicles observed in the first laparoscopy. Serum P4 concentration was determined on days 4, 7, 10, 13, 17 and 21 post FTAI by chemiluminescence. A similar follicular population in size and number was observed in the three experimental groups prior to the beginning of treatments (Follicles 2 mm: 6.4 +/- 3.7, 3 mm: 3.0 +/- 2.3, 4 mm: 1.1 +/- 0.5, 5 mm: 1.4 +/- 0.8; P ? 0.05). The formation of 1.0 +/- 0.4 and 1.1 +/- 0.3 acc-CL was observed in the GnRH and hCG groups, respectively (P ? 0.05), but was not observed in the Control group (P < 0.05). Follicle sizes from which acc-CL generated were 3, 4 and 5 mm and did not differ between hormonal treatments (P ? 0.05). The hCG group had higher mean concentrations of P4 on days 7, 10, 13 and 17 post FTAI compared with the GnRH group and the Control group (P < 0.05), while no differences were observed between these two latter groups (P > 0.05). Mean P4 concentrations in ewes treated with hCG showed no differences according to the size of the follicle from which acc-CL were generated (P ? 0.05). In conclusion, administration of hCG or GnRH on day 4 post FTAI induced the formation of one acc-CL from follicles of 3, 4 or 5 mm, indistinctly. However, serum P4 concentration increased significantly only in the hCG group. The serum P4 concentrations of acc-CL that originated from different follicle sizes did not differ. PMID- 28987890 TI - Adsorption of organic contaminants by graphene nanosheets: A review. AB - Graphene nanosheets (GNS) such as graphenes and graphene oxides (GOs) have been widely investigated as next-generation adsorbents in both water and wastewater treatment processes due to their unique physicochemical properties and their affinity towards different classes of organic contaminants (OCs). In the last five years, more than 40 articles investigating adsorption of different classes of OCs by graphene and GO were published in peer-reviewed journals. Adsorption mechanisms were controlled by molecular properties of OCs (e.g., aromatic vs aliphatic, molecular size and hydrophobicity), characteristics of adsorbents (e.g., surface area, pore size distribution, and surface functional groups), and background solution properties (e.g., pH, ionic strength, surfactants, NOM, and temperature). This literature survey includes: (i) a summary of adsorption of OCs by GNS, (ii) a comprehensive discussion of the mechanisms and factors controlling the adsorption of OCs by GNS and a comparison of their adsorption behaviors with those of CNT. This literature survey also identifies future research needs and challenges on the adsorption of OCs by GNS. PMID- 28987891 TI - Surface-modified microbubbles (colloidal gas aphrons) for nanoparticle removal in a continuous bubble generation-flotation separation system. AB - The treatment of nanoparticle (NP) polluted aqueous suspensions by flotation can be problematic due to the low probability of collision between particles and bubbles. To overcome this limitation, the present work focuses on developing an enhanced flotation technique using the surface-functionalized microbubbles - colloidal gas aphrons (CGAs). The CGA generator was adapted to be air flow rate controlled based on the classical Sebba system; thus it could be well adopted in a continuous flotation process. Cetyl trimethylammonium bromide (CTAB) and sodium dodecyl sulfate (SDS) were employed for CGA creation. Positively surface-charged CTAB-CGAs (~44.1 MUm in size) and negatively surface-charged SDS-CGAs (~42.1 MUm in size) were produced at the optimum stirring speed of 8000 rpm. The half-life of CGAs varied from 100 s to 340 s under the tested conditions, which was largely sufficient for transferring CGAs from bubble generator to flotation cell. The air flow led to less stable CTAB-CGAs but apparently enhanced the stability of SDS CGAs at higher air flow rates. In the presence of air flow, the drainage behavior was not much related to the type of surfactants. The continuous CGA-flotation trials highlighted the effective separation of silica nanoparticles - the removal efficiencies of different types of SiO2 NPs could reach approximately 90%-99%; however, at equivalent surfactant concentrations, no greater than 58% of NPs were removed when surfactants and bubbles were separately added into the flotation cell. The SiO2 NPs with small size were removed more efficiently by the CGA flotation process. For the flotation with CTAB-CGAs, the neutral and basic initial SNP suspension was recommended, whereas the SDS-CGAs remained high flotation efficiency over all investigated pH. The good performance of CGA flotation might be interpreted: most of the surfactant molecules well covered/coated on the surfaces of stable CGAs and thus fully contacted with NPs, resulting in the efficient utilization of surfactants. PMID- 28987892 TI - Teaching global health using crowd-sourcing with Missing Maps. PMID- 28987893 TI - A systematic review of online learning programs for nurse preceptors. AB - BACKGROUND: Nurse preceptors guide students to integrate theory into practice, teach clinical skills, assess clinical competency, and enhance problem solving skills. Managing the dual roles of a registered nurse and preceptor poses tremendous challenges to many preceptors. Online learning is recognized as an effective learning approach for enhancing nursing knowledge and skills. OBJECTIVE: The systematic review aims to review and synthesise the online learning programs for preceptors. DESIGN: A systematic review was designed based on the Cochrane Handbook for Systematic Reviews of Programs. DATA SOURCES: Articles published between January 2000 and June 2016 were sought from six electronic databases: CINAHL, Medline OVID, PubMed, Science Direct, Scopus, and Web of Science. METHODS: All papers were reviewed and quality assessment was performed. Nine studies were finally selected. Data were extracted, organized and analysed using a narrative synthesis. RESULTS: The review identified five overarching themes: development of the online learning programs for nurse preceptors, major contents of the programs, uniqueness of each program, modes of delivery, and outcomes of the programs. CONCLUSION: The systematic review provides insightful information on educational programs for preceptors. At this information age, online learning offers accessibility, convenience, flexibility, which could of great advantage for the working adults. In addition, the online platform provides an alternative for preceptors who face challenges of workload, time, and support system. Therefore, it is paramount that continuing education courses need to be integrated with technology, increase the flexibility and responsiveness of the nursing workforce, and offer alternative means to take up courses. PMID- 28987894 TI - Students nurses' knowledge and prevalence of Needle Stick Injury in Jordan. AB - BACKGROUND: Student nurses are at high risk of blood-borne pathogens transmitted via Needle Stick Injury (NSI). Understanding various aspects of NSI is essential if they are to avoid the risks associated with it. OBJECTIVES: The study was conducted to measure student nurses' level of knowledge about NSI and to examine its prevalence and post-exposure measures in Jordan. DESIGN: A cross-sectional and descriptive design was used. SAMPLE AND SETTING: A sample of 279 student nurses studying at one private and four government universities distributed throughout Jordan. METHOD: The study used an online survey composed of 22 questions developed from NSI literature. The questionnaire was divided into three parts: background, to measure students' demographics; knowledge, to measure nurses' understanding of NSI; and prevalence, to measure exposure to NSI and the follow-up measures. Student nurses were recruited through Facebook. The survey was available online for one full semester in 2016/2017. RESULTS: The total number of completed surveys was 279 (response rate=61%). Most of the students were female (n=198; 71%), in their fourth year (n=114; 40.9%). Their mean age was 21years (SD=2.5). The mean score for the knowledge part was 7 out of 10 (SD=1.7). Almost a third of the students had at least one incident of exposure to NSI (n=73; 26.2%). Most of the students who had suffered NSI did not inform their clinical instructors (67.1%) or write an incident report (86.3%). The results showed that there was no significant difference in the knowledge total scores between males and females or between students across different universities. However, a significant difference was found between students in different years of study (F (276, 2)=6.77, p=0.001). CONCLUSION: Student nurses in Jordan have a moderate understanding of issues regarding NSI. This knowledge improved with seniority. However, exposure to NSI and its under-reporting is a prevalent problem. This study recommends focusing on NSI in the nursing curriculum, and providing more protection and post-exposure intervention for students during their clinical practice. PMID- 28987895 TI - Evaluating best educational practices, student satisfaction, and self-confidence in simulation: A descriptive study. AB - BACKGROUND: The National League for Nursing (NLN) has endorsed simulation as a necessary teaching approach to prepare students for the demanding role of professional nursing. Questions arise about the suitability of simulation experiences to educate students. Empirical support for the effect of simulation on patient outcomes is sparse. Most studies on simulation report only anecdotal results rather than data obtained using evaluative tools. OBJECTIVES: The aim of this study was to examine student perception of best educational practices in simulation and to evaluate their satisfaction and self-confidence in simulation. DESIGN: This study was a descriptive study designed to explore students' perceptions of the simulation experience over a two-year period. Using the Jeffries framework, a Simulation Day was designed consisting of serial patient simulations using high and medium fidelity simulators and live patient actors. SETTING: The setting for the study was a regional campus of a large Midwestern Research 2 university. PARTICIPANTS: The convenience sample consisted of 199 participants and included sophomore, junior, and senior nursing students enrolled in the baccalaureate nursing program. METHODS: The Simulation Days consisted of serial patient simulations using high and medium fidelity simulators and live patient actors. Participants rotated through four scenarios that corresponded to their level in the nursing program. Data was collected in two consecutive years. Participants completed both the Educational Practices Questionnaire (Student Version) and the Student Satisfaction and Self-Confidence in Learning Scale. RESULTS: Results provide strong support for using serial simulation as a learning tool. Students were satisfied with the experience, felt confident in their performance, and felt the simulations were based on sound educational practices and were important for learning. CONCLUSIONS: Serial simulations and having students experience simulations more than once in consecutive years is a valuable method of clinical instruction. When conducted well, simulations can lead to increased student satisfaction and self-confidence. PMID- 28987896 TI - Using reusable learning objects (RLOs) in wound care education: Undergraduate student nurse's evaluation of their learning gain. AB - BACKGROUND: Both nationally and internationally concerns have been expressed over the adequacy of preparation of undergraduate nurses for the clinical skill of wound care. This project describes the educational evaluation of a series of Reusable Learning Objects (RLOs) as a blended learning approach to facilitate undergraduate nursing students learning of wound care for competence development. Constructivism Learning Theory and Cognitive Theory of Multimedia Learning informed the design of the RLOs, promoting active learner approaches. Clinically based case studies and visual data from two large university teaching hospitals provided the authentic learning materials required. Interactive exercises and formative feedback were incorporated into the educational resource. METHODS: Evaluation of student perceived learning gains in terms of knowledge, ability and attitudes were measured using a quantitative pre and posttest Wound Care Competency Outcomes Questionnaire. The RLO CETL Questionnaire was used to identify perceived learning enablers. Statistical and deductive thematic analyses inform the findings. RESULTS: Students (n=192) reported that their ability to meet the competency outcomes for wound care had increased significantly after engaging with the RLOs. Students rated the RLOs highly across all categories of perceived usefulness, impact, access and integration. CONCLUSION: These findings provide evidence that the use of RLOs for both knowledge-based and performance based learning is effective. RLOs when designed using clinically real case scenarios reflect the true complexities of wound care and offer innovative interventions in nursing curricula. PMID- 28987897 TI - Does Preceptorship improve confidence and competence in Newly Qualified Nurses: A systematic literature review. AB - AIM: A systematic literature review to assess whether preceptorship improves confidence and competence in Newly Qualified Nurses. BACKGROUND: Preceptorship was introduced into nursing in the United Kingdom in 1991 with the original aim to improve competence and confidence. This systematic review was undertaken to review the evidence of the impact of preceptorship on confidence and competence of nurses in their first year post qualifying. DATA SOURCES: A comprehensive search of The British Nursing Index, CINAHL, Embase, Medline, PsycInfo, PyscArticles, Campbell Collaboration; Cochrane, HMIC, ERIC, ASSIA, Web of Science, Scopus, Scopus Conference, Web of Science Conferences; NHS Evidence, OpenGrey, National Technical, NINR, Opendoar, SSRN, Kings College London and the RCN was conducted. METHODS: A PRISMA structured systematic review was carried out, 14 papers 4 mixed methods, 8 qualitative, 1 scoping review and 1 service development, published between 1996 and 2013 were critically reviewed, and data extracted using thematic analysis. RESULTS: Four themes were identified from a thematic analysis: measurement, knowledge and experience, support, and structure. CONCLUSION: While one-to-one preceptorship does influence confidence and competence, Preceptorship Programmes has greater impact than the individual preceptor. Due to limited empirical research there is no concrete evidence that Preceptorship has a direct impact on confidence or competence. Further research into team preceptorship/choice of preceptors and what impacts on Newly Qualified Nurses confidence and competence is required. PMID- 28987898 TI - Behavioral and cortisol responses to stress in newborn infants: Effects of mode of delivery. AB - Suboptimal birth characteristics have been associated with altered reactivity to stress in infants. However, previous studies have not controlled for mode of delivery, which may influence the neonatal onset of stress responses. The present study assessed stress-related behavior and salivary cortisol before and after an inoculation at two hours after birth, and compared infants born through VD (N=70) and elective CS (N=72). The results indicated that overall stress behavior and body movements were increased immediately after inoculation in infants born through CS compared to VD. Infants born through CS did not show significant cortisol increases following inoculation and their overall cortisol reactivity (i.e., AUCG) was lower compared to infants born through VD. However, unexpectedly, cortisol levels in infants born through VD were highest before inoculation and subsequently decreased. Cortisol was significantly related to behavior in both groups, but in opposite directions. These results support the view that mode of delivery influences neonatal stress reactivity, although future studies should try to disentangle the effects of mode of delivery and related variables. PMID- 28987899 TI - Plasma lipoproteins in posttraumatic stress disorder patients compared to healthy controls and their associations with the HPA- and HPT-axis. AB - BACKGROUND: Based on studies among primarily male veteran subjects, lipoproteins are thought to mediate the association of posttraumatic stress disorder (PTSD) with cardiovascular disease (CVD). However, recent civilian studies with female samples or samples with both sexes represented provide little evidence for this association. Gender, diet and sex-specific effects of stress hormones on lipoproteins may explain this dissociation in findings. METHOD: Cross-sectional analysis of plasma concentrations of total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglycerides (TG) in a male and female sample of 49 PTSD-patients due to civilian trauma and 45 healthy controls. Second, we related these lipoproteins to several stress hormones (prolactin, cortisol, DHEA(S), TSH, T4). RESULTS: Patients showed lower LDL (p=0.033) and LDL:HDL ratio (p=0.038) compared to controls, also when adjusting for diet. Sex influenced the effect of having PTSD on LDL with only male patients having lower values than male controls (p=0.012). All stress hormones were associated with several lipoproteins, mostly in a sex-dependent manner. For LDL, a significant sex-by-cortisol effect (p<0.001), having PTSD-by-sex-by-DHEA (p<0.001), having PTSD-by-sex-by-DHEAS (p=0.016) and having PTSD-by-sex-by prolactin (p=0.003) was found. CONCLUSION: In this male and female civilian sample we found a somewhat more favorable lipoprotein profile in PTSD-patients in contrast to evidence from strictly male veteran samples exhibiting a less favorable lipoprotein profile. Male patients did not exhibit a worse lipoprotein profile than female patients and therefore gender cannot explain the contradiction in evidence. Additionally, we found that PTSD-related stress hormones are associated with lipoproteins levels in patients in a sex-specific manner. Specific configurations of stress hormones may contribute to CVD in male patients or protect in female patients. Further research on these configurations could indicate which PTSD-patients are especially at risk for CVD and which are not. This could guide future precision medicine efforts to prevent and treat the still growing burden of CVD morbidity and mortality in PTSD. PMID- 28987900 TI - Cardiorespiratory Responses to Pool Floor Walking in People Poststroke. AB - OBJECTIVE: To compare cardiorespiratory responses between pool floor walking and overground walking (OW) in people poststroke. DESIGN: Cross-sectional study. SETTING: University-based therapeutic exercise facility. PARTICIPANTS: Participants (N=28) were comprised of 14 community-dwelling individuals poststroke (5.57+/-3.57y poststroke) and 14 age- and sex-matched healthy adults (mean age, 58.00+/-15.51y; male/female ratio, 9:5). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: A telemetric metabolic system was used to collect cardiorespiratory variables, including oxygen consumption (Vo2), energy expenditure (EE), and expired volume per unit time (Ve), during 6-minute walking sessions in chest-depth water and on land at a matched speed, determined by average of maximum walking speed in water. RESULTS: Individuals poststroke elicited no significant differences in cardiorespiratory responses between pool floor walking and OW. However, healthy controls showed significant increases in mean Vo2 values by 94%, EE values by 109%, and Ve values by 94% (all P<.05) during pool floor walking compared with OW. A 2*2 mixed model analysis of variance revealed a significant group * condition interaction in Vo2, in which the control group increased Vo2 from OW to pool floor walking, whereas the stroke group did not. CONCLUSIONS: Our results indicate that people poststroke, unlike healthy adults, do not increase EE while walking in water compared with on land. Unlike stationary walking on an aquatic treadmill, forward locomotion during pool floor walking at faster speeds may have increased drag force, which requires greater EE from healthy adults. Without demanding excessive EE, walking in water may offer a naturally supportive environment for gait training in the early stages of rehabilitation. PMID- 28987901 TI - Quality of Relationships With Caregivers, Depression, and Life Satisfaction After Dysvascular Lower Extremity Amputation. AB - OBJECTIVE: To describe the relationship between caregiver-specific support and conflict, and psychosocial outcomes among individuals experiencing their first dysvascular lower extremity amputation (LEA). DESIGN: Cross-sectional cohort study using self-report surveys. SETTING: Department of Veterans Affairs, academic medical center, and level I trauma center. PARTICIPANTS: Individuals undergoing their first major LEA because of complications of peripheral arterial disease (PAD) or diabetes who have a caregiver and completed measures of caregiver support and conflict (N=137; 94.9% men). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The Patient Health Questionnaire-9 to assess depression and the Satisfaction With Life Scale to assess life satisfaction. RESULTS: In multiple regression analyses, controlling for global levels of perceived support, self-rated health, age, and mobility, caregiver-specific support was found to be associated with higher levels of life satisfaction and caregiver-specific conflict was found to be associated with lower levels of life satisfaction and higher levels of depressive symptoms. CONCLUSIONS: The specific relationship between individuals with limb loss and their caregivers may be an important determinant of well-being. Conflict with caregivers, which has received little attention thus far in the limb loss literature, appears to play a particularly important role. Individuals with limb loss may benefit from interventions with their caregivers that both enhance support and reduce conflict. PMID- 28987902 TI - Comparison of Ultrasonography and Short-Segment Nerve Conduction Study in Ulnar Neuropathy at the Elbow. AB - OBJECTIVE: To assess the correlation between ultrasonographic and electrodiagnostic findings to determine the localization of the ulnar trapping at the elbow. DESIGN: Cross-sectional and noninterventional trial. SETTING: Physical medicine and rehabilitation department of a teaching hospital. PARTICIPANTS: Patients (N=14) diagnosed with ulnar nerve entrapment using short-segment nerve conduction study. INTERVENTIONS: The elbow area was divided into 4 segments with 2-cm intervals. All patients underwent ultrasonographic and electrodiagnostic examinations. MAIN OUTCOME MEASURES: The nerve conduction velocity (NCV) of each segment was measured. The cross-sectional area (CSA) of the ulnar nerve was measured at 5 levels. The proximal CSA/distal CSA ratio (PDR) was calculated by proportioning the CSA values for each segment. The highest PDR was accepted as a trapping segment, whereas the segment with the lowest NCV was accepted electrophysiologically (provided it was <50m/s). RESULTS: A total of 80 PDR and NCV measurements were taken from 20 elbows. A statistically significant negative correlation (r=-.554; P<.001) was found between general PDR and NCV values. When we assumed that the NCV value <50m/s as the criterion standard for diagnosis, the cutoff value for the PDR was found to be 1.08, with a sensitivity of 70% and a specificity of 92.5%. The minimum NCV value and the maximum PDR value were mostly seen in the third segment compatible with the cubital tunnel. CONCLUSIONS: Ultrasonography seems to be advantageous because it is more comfortable for the patient and requires shorter time than does electroneuromyography. To our knowledge, this is the first study to detect ulnar nerve entrapment by using not only CSA but also PDR as a ratio method with ultrasound. PMID- 28987903 TI - Full left ventricle quantification via deep multitask relationships learning. AB - Cardiac left ventricle (LV) quantification is among the most clinically important tasks for identification and diagnosis of cardiac disease. However, it is still a task of great challenge due to the high variability of cardiac structure across subjects and the complexity of temporal dynamics of cardiac sequences. Full quantification, i.e., to simultaneously quantify all LV indices including two areas (cavity and myocardium), six regional wall thicknesses (RWT), three LV dimensions, and one phase (Diastole or Systole), is even more challenging since the ambiguous correlations existing among these indices may impinge upon the convergence and generalization of the learning procedure. In this paper, we propose a deep multitask relationship learning network (DMTRL) for full LV quantification. The proposed DMTRL first obtains expressive and robust cardiac representations with a deep convolution neural network (CNN); then models the temporal dynamics of cardiac sequences effectively with two parallel recurrent neural network (RNN) modules. After that, it estimates the three types of LV indices under a Bayesian framework that is capable of learning multitask relationships automatically, and estimates the cardiac phase with a softmax classifier. The CNN representation, RNN temporal modeling, Bayesian multitask relationship learning, and softmax classifier establish an effective and integrated network which can be learned in an end-to-end manner. The obtained task covariance matrix captures the correlations existing among these indices, therefore leads to accurate estimation of LV indices and cardiac phase. Experiments on MR sequences of 145 subjects show that DMTRL achieves high accurate prediction, with average mean absolute error of 180 mm2, 1.39 mm, 2.51 mm for areas, RWT, dimensions and error rate of 8.2% for the phase classification. This endows our method a great potential in comprehensive clinical assessment of global, regional and dynamic cardiac function. PMID- 28987904 TI - Bilateral parietal activations for complex visual-spatial functions: Evidence from a visual-spatial construction task. AB - In this paper, we examine brain lateralization patterns for a complex visual spatial task commonly used to assess general spatial abilities. Although spatial abilities have classically been ascribed to the right hemisphere, evidence suggests that at least some tasks may be strongly bilateral. For example, while functional neuroimaging studies show right-lateralized activations for some spatial tasks (e.g., line bisection), bilateral activations are often reported for others, including classic spatial tasks such as mental rotation. Moreover, constructive apraxia has been reported following left- as well as right hemisphere damage in adults, suggesting a role for the left hemisphere in spatial function. Here, we use functional neuroimaging to probe lateralization while healthy adults carry out a simplified visual-spatial construction task, in which they judge whether two geometric puzzle pieces can be combined to form a square. The task evokes strong bilateral activations, predominantly in parietal and lateral occipital cortex. Bilaterality was observed at the single-subject as well as at the group level, and regardless of whether specific items required mental rotation. We speculate that complex visual-spatial tasks may generally engage more bilateral activation of the brain than previously thought, and we discuss implications for understanding hemispheric specialization for spatial functions. PMID- 28987905 TI - Neural processing of musical meter in musicians and non-musicians. AB - Musical sounds, along with speech, are the most prominent sounds in our daily lives. They are highly dynamic, yet well structured in the temporal domain in a hierarchical manner. The temporal structures enhance the predictability of musical sounds. Western music provides an excellent example: while time intervals between musical notes are highly variable, underlying beats can be realized. The beat-level temporal structure provides a sense of regular pulses. Beats can be further organized into units, giving the percept of alternating strong and weak beats (i.e. metrical structure or meter). Examining neural processing at the meter level offers a unique opportunity to understand how the human brain extracts temporal patterns, predicts future stimuli and optimizes neural resources for processing. The present study addresses two important questions regarding meter processing, using the mismatch negativity (MMN) obtained with electroencephalography (EEG): 1) how tempo (fast vs. slow) and type of metrical structure (duple: two beats per unit vs. triple: three beats per unit) affect the neural processing of metrical structure in non-musically trained individuals, and 2) how early music training modulates the neural processing of metrical structure. Metrical structures were established by patterns of consecutive strong and weak tones (Standard) with occasional violations that disrupted and reset the structure (Deviant). Twenty non-musicians listened passively to these tones while their neural activities were recorded. MMN indexed the neural sensitivity to the meter violations. Results suggested that MMNs were larger for fast tempo and for triple meter conditions. Further, 20 musically trained individuals were tested using the same methods and the results were compared to the non-musicians. While tempo and meter type similarly influenced MMNs in both groups, musicians overall exhibited significantly reduced MMNs, compared to their non-musician counterparts. Further analyses indicated that the reduction was driven by responses to sounds that defined the structure (Standard), not by responses to Deviants. We argue that musicians maintain a more accurate and efficient mental model for metrical structures, which incorporates occasional disruptions using significantly fewer neural resources. PMID- 28987906 TI - Visually evoked responses from the blind field of hemianopic patients. AB - Hemianopia is a visual field defect characterized by decreased vision or blindness in the contralesional visual field of both eyes. The presence of well documented above-chance unconscious behavioural responses to visual stimuli presented to the blind hemifield (blindsight) has stimulated a great deal of research on the neural basis of this important phenomenon. The present study is concerned with electrophysiological responses from the blind field. Since previous studies found that transient Visual Evoked Potentials (VEPs) are not entirely suitable for this purpose here we propose to use Steady-State VEPs (SSVEPs). A positive result would have important implications for the understanding of the neural bases of conscious vision. We carried out a passive SSVEP stimulation with healthy participants and hemianopic patients. Stimuli consisted of four black-and-white sinusoidal Gabor gratings presented one in each visual field quadrant and flickering one at a time at a 12Hz rate. To assess response reliability a Signal-to-Noise Ratio analysis was conducted together with further analyses in time and frequency domains to make comparisons between groups (healthy participants and patients), side of brain lesion (left and right) and visual fields (sighted and blind). The important overall result was that stimulus presentation to the blind hemifield yielded highly reliable responses with time and frequency features broadly similar to those found for cortical extrastriate areas in healthy controls. Moreover, in the intact hemifield of hemianopics and in healthy controls there was evidence of a role of prefrontal structures in perceptual awareness. Finally, the presence of different patterns of brain reorganization depended upon the side of lesion. PMID- 28987908 TI - Early use of phonological codes in deaf readers: An ERP study. AB - Previous studies suggest that deaf readers use phonological information of words when it is explicitly demanded by the task itself. However, whether phonological encoding is automatic remains controversial. The present experiment examined whether adult congenitally deaf readers show evidence of automatic use of phonological information during visual word recognition. In an ERP masked priming lexical decision experiment, deaf participants responded to target words preceded by a pseudohomophone (koral - CORAL) or an orthographic control prime (toral - CORAL). Responses were faster for the pseudohomophone than for the orthographic control condition. The N250 and N400 amplitudes were reduced for the pseudohomophone when compared to the orthographic control condition. Furthermore, the magnitude of both the behavioral and the ERP pseudohomophone effects in deaf readers was similar to that of a group of well-matched hearing controls. These findings reveal that phonological encoding is available to deaf readers from the early stages of visual word recognition. Finally, the pattern of correlations of phonological priming with reading ability suggested that the amount of sub lexical use of phonological information could be a main contributor to reading ability for hearing but not for deaf readers. PMID- 28987907 TI - Left caudal middle frontal gray matter volume mediates the effect of age on self initiated elaborative encoding strategies. AB - Aging is associated with decreased self-initiated use of effective elaborative encoding strategies. Little is currently known regarding what factors drive age differences in self-initiated encoding strategies. The present research investigated whether age differences in prefrontal gray matter integrity contribute to age differences in self-initiated elaborative encoding strategies. The relationships between age, prefrontal regional gray matter volumes, and overall use of self-initiated elaborative encoding strategies were examined in healthy younger and older adults. Gray matter volume was calculated from structural MRI scans using Freesurfer. Encoding strategy use was assessed by retrospective item-by-item strategy self-reports given after a verbal intentional encoding task. Left caudal middle frontal gray matter volume mediated the effect of age on overall self-initiated use of elaborative encoding strategies. This suggests that age-associated declines in prefrontal gray matter integrity significantly contribute to age-associated declines in effective encoding strategies. PMID- 28987910 TI - Exploring the neural substrates of misinformation processing. AB - It is well known that information that is initially thought to be correct but then revealed to be false, often continues to influence human judgement and decision making despite people being aware of the retraction. Yet little research has examined the underlying neural substrates of this phenomenon, which is known as the 'continued influence effect of misinformation' (CIEM). It remains unclear how the human brain processes critical information that retracts prior claims. To address this question in further detail, 26 healthy adults underwent functional magnetic resonance imaging (fMRI) while listening to brief narratives which either involved a retraction of prior information or not. Following each narrative, subjects' comprehension of the narrative, including their inclination to rely on retracted information, was probed. As expected, it was found that retracted information continued to affect participants' narrative-related reasoning. In addition, the fMRI data indicated that the continued influence of retracted information may be due to a breakdown of narrative-level integration and coherence-building mechanisms implemented by the precuneus and posterior cingulate gyrus. PMID- 28987909 TI - Event-related brain potentials reveal age-related changes in parafoveal-foveal integration during sentence processing. AB - Normative aging is associated with deficits in visual acuity and cognitive control that impact the allocation of visual attention, but little is known about how those changes affect information extraction and integration during visual language comprehension in older adulthood. In the current study, we used a visual hemi-field flanker RSVP paradigm with event-related brain potentials to study how older readers process fine-grained aspects of semantic expectancy in parafoveal and foveal vision. Stimuli consisted of high constraint sentences with expected, unexpected but plausible, or anomalous parafoveal target words, as well as low constraint sentences with neutral but expected target words. Older adults showed graded parafoveal N400 effects that were strikingly similar to younger readers, indicating intact parafoveal semantic processing. However, whereas young adults were able to use this parafoveal pre-processing to facilitate subsequent foveal viewing, resulting in a reduced foveal N400 effect, older adults were not able to. Instead, older adults re-processed the semantics of words in foveal vision, resulting in a larger foveal N400 effect relative to the young. Collectively, our findings suggest that although parafoveal semantic processing per se is preserved in aging, there exists an age-related deficit in the ability to rapidly integrate parafoveal and foveal visual semantic representations. PMID- 28987911 TI - Assessment of tobacco heating product THP1.0. Part 5: In vitro dosimetric and cytotoxic assessment. AB - Tobacco heating products (THPs) represent a subset of the next-generation nicotine and tobacco product category, in which tobacco is typically heated at temperatures of 250-350 degrees C, thereby avoiding many of the harmful combustion-related toxicant emissions of conventional cigarettes. In this study, we have assessed aerosol generation and cytotoxicity from two commercially available THPs, THP1.0 and THS, relative to tobacco smoke from 3R4F reference cigarettes, using an adapted Borgwaldt RM20S Smoking Machine. Quantification of nicotine in the exposed cell-culture media showed greater delivery of nicotine from both THPs than from the cigarette. Using Neutral Red Uptake assay, THPs demonstrated reduced in vitro cytotoxicity in H292 human bronchial epithelial cells as compared with 3R4F cigarette exposure at the air-liquid interface (p < 0.0001). Both THPs demonstrated a statistically similar reduction in biological response, with >87% viability relative to 3R4F at a common aerosol dilution (1:40, aerosol:air). A similar response was observed when plotted against nicotine; a statistical difference between 3R4F and THPs (p < 0.0001) and no difference between the THPs (p = 0.0186). This pre-clinical in vitro biological testing forms part of a larger package of data to help assess the safety and risk reduction potential of next-generation tobacco products relative to cigarettes, using a weight of evidence approach. PMID- 28987912 TI - Framework for the quality assurance of 'omics technologies considering GLP requirements. AB - 'Omics technologies are gaining importance to support regulatory toxicity studies. Prerequisites for performing 'omics studies considering GLP principles were discussed at the European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) Workshop Applying 'omics technologies in Chemical Risk Assessment. A GLP environment comprises a standard operating procedure system, proper pre-planning and documentation, and inspections of independent quality assurance staff. To prevent uncontrolled data changes, the raw data obtained in the respective 'omics data recording systems have to be specifically defined. Further requirements include transparent and reproducible data processing steps, and safe data storage and archiving procedures. The software for data recording and processing should be validated, and data changes should be traceable or disabled. GLP-compliant quality assurance of 'omics technologies appears feasible for many GLP requirements. However, challenges include (i) defining, storing, and archiving the raw data; (ii) transparent descriptions of data processing steps; (iii) software validation; and (iv) ensuring complete reproducibility of final results with respect to raw data. Nevertheless, 'omics studies can be supported by quality measures (e.g., GLP principles) to ensure quality control, reproducibility and traceability of experiments. This enables regulators to use 'omics data in a fit-for-purpose context, which enhances their applicability for risk assessment. PMID- 28987913 TI - Phages as friends and enemies in food processing. AB - Phages can infect all bacterial genera on the planet leading to their abundance in ecosystems. While these bacterial viruses may represent a risk to industrial fermentations, they may also be valuable tools to control foodborne pathogens. Here we review these two sides of phage replication. As bacterial fermentations are constantly under threat of phage attacks, we will discuss phage diversity and industrial strategies employed to reduce their impact on food processing. Furthermore, we will explore the use of pathogen-infecting phages to reduce the risks associated with foodborne diseases. PMID- 28987914 TI - Functions of triacylglycerols during plant development and stress. AB - Plant oil in the form of triacylglycerols (TAGs) is a major storage compound used as food, feed and sustainable feedstock for biofuel production. Recent findings suggest that TAGs are more than a carbon and energy reserve in seeds and other storage tissues. In vegetative tissues, TAG metabolism is involved in cell division and expansion, stomatal opening, and membrane lipid remodeling. Moreover, in reproductive tissues, TAGs are important for both organ formation and successful pollination. Here we provide a brief overview of the physiological function and contribution of TAGs during plant development under optimal and varying environmental conditions. These roles of TAGs need to be considered during engineering attempts to further improve TAG content in different tissues. PMID- 28987915 TI - Non-invasive molecular imaging and theranostic probes. PMID- 28987916 TI - Sequential Sedimentation-Biofiltration System for the purification of a small urban river (the Sokolowka, Lodz) supplied by stormwater. AB - The study analyses the efficiency of a Sequentional Sedimentation-Biofiltration System (SSBS) built on the Sokolowka river in Lodz (Poland). It was constructed to purify a small urban river whose hydrological regime is dominated by stormwater and meltwater. The SSBS was constructed on a limited area as multi zone constructed wetlands. The SSBS consists of three zones: sedimentation zone with structures added to improve sedimentation, a geochemical barrier made of limestone deposit and biofiltration zone. The purification processes of total suspended solids (TSS), total phosphorus (TP), total nitrogen (TP) and other nutrients: phosphates (PO43-), ammonium (NH4+) and nitrates (NO3-) of the SSBS were analyzed. Chloride (Cl-) reduction was investigated. Monitoring conducted in the first two hydrological years after construction indicated that the SSBS removed 61.4% of TSS, 37.3% of TP, 30.4% of PO43-, 46.1% of TN, 2.8% of NH4+, 44.8% of NO3- and 64.0% of Cl-. The sedimentation zone played a key role in removing TSS and nutrients. The geochemical barrier and biofiltration zone each significantly improved overall efficiency by 4-10% for TSS, PO43-, TN, NO3- and Cl-. Although the system reduced the concentration of chloride, further studies are needed to determine the circulation of Cl- in constructed wetlands (CWs), and to assess its impact on purification processes. PMID- 28987917 TI - An evaluation of odor repellent effectiveness in prevention of wildlife-vehicle collisions. AB - Wildlife-vehicle collisions (WVC) amount to 11% of all registered traffic crashes in the Czech Republic causing, apart from numerous deaths and serious injuries to animals, property damage and injuries to car passengers. Odor repellents have the potential to lower the overall number of WVC and allow animals to cross roads at the same time. We tested the effectiveness of odor repellent preparation in prevention of WVC. 18 places were selected on the Czech road network where WVC were concentrated on the basis of traffic crash data. Control sections on the same road segments were also delimited in order to keep the traffic intensities constant. We applied a Before-After-Control-Impact (BACI) study design to control not only the effect of the measures but also the expected natural variations in wildlife populations over time. Data were compared before and after odor repellent installations. Wildlife carcass gathering was carried out during the spring and autumn. We also used the police crash database to supplement carcass data when no field works were carried out. 201 killed mammals (roe deer and wild boars) were identified in total over 47 months. We applied a Bayesian approach as only a limited numbers of WVC were available. A WVC decrease between 26 - 43% can be expected on the treated road sections. These numbers are, however, up to three times lower than those claimed by producers of odor preparations. PMID- 28987918 TI - Screen for Disordered Eating: Improving the accuracy of eating disorder screening in primary care. AB - OBJECTIVE: To develop a primary care eating disorder screen with greater accuracy and greater potential for generalizability, compared to existing screens. DESIGN: Cross-sectional survey to assess discriminative accuracy of a new screen, Screen for Disordered Eating (SDE), compared to Eating Disorders Screen for Primary Care (EDS-PC) and SCOFF screener, using prevalence rates of Binge Eating Disorder (BED), Bulimia Nervosa (BN), Anorexia Nervosa (AN), and Any Eating Disorder (AED), as measured by the Eating Disorder Examination Questionnaire (EDE-Q). RESULTS: The SDE correctly classified 87.2% (CI: 74.3%-95.2%) of BED cases, all cases of BN and AN, and 90.5% (CI: 80.4%-96.4%) of AED cases. Sensitivity estimates were higher than the SCOFF, which correctly identified 69.6% (CI: 54.2% 82.3%) of BED, 77.8% (CI: 40.0%-97.2%) of BN, 37.5% (CI: 8.52%-75.5%) of AN, and 66.1% (CI: 53%-77.7%) of AED. While the EDS-PC had slightly higher sensitivity than the SDE, the SDE had better specificity. The SDE outperformed the SCOFF in classifying true cases, the EDS-PC in classifying true non-cases, and the EDS-PC in distinguishing cases from non-cases. CONCLUSIONS: The SDE is the first screen, inclusive of BED, valid for detecting eating disorders in primary care. Findings have broad implications to address eating disorder screening in primary care settings. PMID- 28987919 TI - Sedentary behavior and anxiety: Association and influential factors among 42,469 community-dwelling adults in six low- and middle-income countries. AB - OBJECTIVE: This study investigated the association between sedentary behavior (SB) and anxiety, and explored factors that influence this relationship in six low- and middle-income countries. METHOD: Cross-sectional data were analyzed from the World Health Organization's Study on Global Ageing and Adult Health. Multivariable linear and logistic regression analyses were conducted to assess the association between anxiety and self-reported SB. Potentially influential factors were examined with mediation analysis. RESULTS: The sample consisted of 42,469 adults aged>=18years (50.1% female; mean age 43.8years). After adjusting for sociodemographics and country, people with anxiety engaged in 24 (95%CI=7-41) more minutes per day of SB than non-anxious individuals; the corresponding figure for the elderly (>=65years) was much higher (55min; 95% CI=29-81). Anxiety was associated with a 2.0 (95%CI=1.5-2.7) times higher odds for high SB (i.e., >=8h/day). Overall, the largest proportion of the high SB-anxiety relationship was explained by mobility limitations (46.8%), followed by impairments in sleep/energy (44.9%), pain/discomfort (31.7%), disability (27.0%), cognition (13.3%), and physical activity levels (6.3%). CONCLUSIONS: Anxiety was significantly associated with high SB, particularly among older adults. Future longitudinal studies are warranted to disentangle the potentially complex interplay of factors that may influence the anxiety-SB relationship. PMID- 28987920 TI - Changes in depression status during the year after breast cancer surgery and impact on quality of life and functioning. AB - OBJECTIVE: Although breast cancer patients' depression changes over time, most longitudinal studies have assessed the influence of only baseline depression on quality of life (QoL). Therefore, this study investigated the influence of changes in depression status on QoL in the year after surgery. METHODS: Participants were interviewed at 2-5days and at 1year after surgery. Depression was diagnosed at both time points, and participants were classified into four groups: no, recovered, incident, and persistent depression. QoL-related functioning and symptoms were evaluated with the EORTC QLQ-C30 questionnaire and the interaction of depression and QoL was analyzed using a repeated-measures analysis of covariance (RMANCOVA). RESULTS: Of the 306 participants, 247 were evaluated at 1year after surgery; 165 had no depression, 40 had recovered from depression, 24 had incident depression, and 18 had persistent depression. The RMANCOVA revealed significant time-by-group interactions; the no-depression group exhibited better recovery in general QoL and functioning, whereas the persistent depression group showed the worst recovery. QoL and functioning improved in the recovered depression group, but worsened in the group with incident depression. CONCLUSIONS: The different impacts of changes in depression status on QoL highlight the importance of periodic screening for depression. PMID- 28987921 TI - TKA patients with unsatisfying knee function show changes in neuromotor synergy pattern but not joint biomechanics. AB - Nearly 20% of patients who have undergone total knee arthroplasty (TKA) report persistent poor knee function. This study explores the idea that, despite similar knee joint biomechanics, the neuro-motor synergies may be different between high functional and low-functional TKA patients. We hypothesized that (1) high functional TKA recruit a more complex neuro-motor synergy pattern compared to low functional TKA and (2) high-functional TKA patients demonstrate more stride-to stride variability (flexibility) in their synergies. Gait and electromyography (EMG) data were collected during level walking for three groups of participants: (i) high-functional TKA patients (n=13); (ii) low-functional TKA patients (n=13) and (iii) non-operative controls (n=18). Synergies were extracted from EMG data using non-negative matrix factorization. Analysis of variance and Spearman correlation analyses were used to investigate between-group differences in gait and neuro-motor synergies. Results showed that synergy patterns were different among the three groups. Control subjects used 5-6 independent neural commands to execute a gait cycle. High functional TKA patients used 4-5 independent neural commands while low-functional TKA patients relied on only 2-3 independent neural commands to execute a gait cycle. Furthermore, stride-to-stride variability of muscles' response to the neural commands was reduced up to 15% in low-functional TKAs compared to the other two groups. PMID- 28987922 TI - The Impact of Systems Biology on Bioprocessing. AB - Bioprocessing offers a sustainable and green approach to the production of chemicals. However, a bottleneck in introducing bioprocesses is cell factory development, which is costly and time-consuming. A systems biology approach can expedite cell factory design by using genome-wide analyses alongside mathematical modeling to characterize and predict cellular physiology. This approach can drive cycles of design, build, test, and learn implemented by metabolic engineers to optimize the cell factory performance. Streamlining of the design phase requires a clearer understanding of metabolism and its regulation, which can be achieved using quantitative and integrated omic characterization, alongside more advanced analytical methods. We discuss here the current impact of systems biology and challenges of closing the gap between bioprocessing and more traditional methods of chemical production. PMID- 28987923 TI - Cognitive costs of decision-making strategies: A resource demand decomposition analysis with a cognitive architecture. AB - Several theories of cognition distinguish between strategies that differ in the mental effort that their use requires. But how can the effort-or cognitive costs associated with a strategy be conceptualized and measured? We propose an approach that decomposes the effort a strategy requires into the time costs associated with the demands for using specific cognitive resources. We refer to this approach as resource demand decomposition analysis (RDDA) and instantiate it in the cognitive architecture Adaptive Control of Thought-Rational (ACT-R). ACT-R provides the means to develop computer simulations of the strategies. These simulations take into account how strategies interact with quantitative implementations of cognitive resources and incorporate the possibility of parallel processing. Using this approach, we quantified, decomposed, and compared the time costs of two prominent strategies for decision making, take-the-best and tallying. Because take-the-best often ignores information and foregoes information integration, it has been considered simpler than strategies like tallying. However, in both ACT-R simulations and an empirical study we found that under increasing cognitive demands the response times (i.e., time costs) of take the-best sometimes exceeded those of tallying. The RDDA suggested that this pattern is driven by greater requirements for working memory updates, memory retrievals, and the coordination of mental actions when using take-the-best compared to tallying. The results illustrate that assessing the relative simplicity of strategies requires consideration of the overall cognitive system in which the strategies are embedded. PMID- 28987924 TI - A response to Sabatino et al 2015 regarding Italian nurse education and practice. PMID- 28987925 TI - Solubilization of the serotonin1A receptor monitored utilizing membrane dipole potential. AB - Solubilization of membrane proteins by amphiphilic detergents represents a crucial step in studies of membrane proteins in which proteins and lipids in natural membranes are dissociated giving rise to mixed clusters of proteins, lipids and detergents in the aqueous dispersion. Although solubilization is a popular method, physicochemical principles underlying solubilization are not well understood. In this work, we monitored solubilization of the bovine hippocampal serotonin1A receptor, a representative member of the GPCR family, using membrane dipole potential measured by a dual fluorescence ratiometric approach with a potential-sensitive fluorophore. Our results show that membrane dipole potential is a good indicator of solubilization and reflects the change in dipolar environment upon solubilization due to dipolar reorganization associated with solubilization. To the best of our knowledge, these results constitute the first report linking membrane dipole potential with solubilization. We envision that these results are potentially useful in providing a molecular mechanism for membrane protein solubilization. PMID- 28987926 TI - Set size manipulations reveal the boundary conditions of perceptual ensemble learning. AB - Recent evidence suggests that observers can grasp patterns of feature variations in the environment with surprising efficiency. During visual search tasks where all distractors are randomly drawn from a certain distribution rather than all being homogeneous, observers are capable of learning highly complex statistical properties of distractor sets. After only a few trials (learning phase), the statistical properties of distributions - mean, variance and crucially, shape - can be learned, and these representations affect search during a subsequent test phase (Chetverikov, Campana, & Kristjansson, 2016). To assess the limits of such distribution learning, we varied the information available to observers about the underlying distractor distributions by manipulating set size during the learning phase in two experiments. We found that robust distribution learning only occurred for large set sizes. We also used set size to assess whether the learning of distribution properties makes search more efficient. The results reveal how a certain minimum of information is required for learning to occur, thereby delineating the boundary conditions of learning of statistical variation in the environment. However, the benefits of distribution learning for search efficiency remain unclear. PMID- 28987928 TI - Synthesis and gelation property of a series of disaccharide triazole derivatives. AB - Low molecular weight gelators are important for the study of supramolecular chemistry and have useful applications for biomaterials. Glycomimetics that are easily accessible and have useful gelation properties are especially interesting molecules. In this research, nine per-O-acetyl lactosyl- and thirteen per-O acetyl maltosyl triazole derivatives were synthesized and analyzed. Most of the maltosyl triazoles and one of the lactosyl derivatives were found to be effective molecular gelators. The supramolecular gels were characterized using rheology and optical microscopy and they exhibited morphologies ranging from fibers to planar sheets. The self-assembling properties of selected lactosyl and maltosyl triazole derivatives were studied using 1H NMR spectroscopy at different temperatures. The NMR studies revealed that the triazole moiety in these compounds played an important role in the formation of the supramolecular assembly, but the sugar moiety configurations are more influential towards gelation. Naproxen and chloramphenicol were used as the model drugs to assess the potential of these compounds in drug delivery applications. A pH responsive gelator showed faster delivery of chloramphenicol at mild basic conditions than neutral conditions. The effective disaccharide triazole-based molecular gelators are useful for the preparation of advanced soft materials that have potential applications as matrix for immobilization of drugs or biomolecules. PMID- 28987929 TI - Assessing notions of denormalization and renormalization of smoking in light of e cigarette regulation. AB - The rationale for 'denormalization' of smoking in tobacco policies has been challenged by the emergence of e-cigarettes and the need to regulate e-cigarette use and promotion. Our aim is to assess the research status on e-cigarettes' contribution to 'renormalization' of smoking and to clarify how renormalization of smoking can be appraised at the conceptual and empirical level. Combining conceptual analysis and narrative review, the paper brings out three dimensions of denormalization/renormalization of smoking ('unacceptability/acceptability'; 'invisibility/visibility'; 'phasing out behaviour/maintaining behaviour') and an inherent duality of the e-cigarette as a smoking-like device and a smoking alternative. These analytical dimensions are applied qualitatively to consider the literature identified by searching the Web of Science database for 'e cigarettes AND renormalization' (and variants thereof). Theoretically, normative changes in smoking acceptability, increased visibility of e-cigarettes and use, and observations of actual use (prevalence, dual use, gateway) can all be applied to illustrate processes of renormalization. However, only acceptability measures and user measures can be said to be empirical tests of renormalization effects. Visibility measures are only based on logical assumptions of a possible renormalization; they are not in themselves indicative of any "real" renormalization effects and can just as well be understood as possible consequences of normalization of e-cigarettes. Just as a downward trend in smoking prevalence is the litmus test of whether denormalization policy works, stagnating or rising smoking prevalence should be the main empirical indicator of renormalization. PMID- 28987930 TI - Impact of New Drugs on the Long-Term Follow-Up of Upfront Tandem Autograft Allograft in Multiple Myeloma. AB - Before the introduction of "new drugs," we designed a trial in which 162 newly diagnosed myeloma patients were biologically randomized to receive either an autologous stem cell transplant (auto-SCT) followed by a nonmyeloablative allogeneic stem cell transplant (allo-SCT) or a double auto-SCT. Fifty-eight patients in the allo-SCT arm and 46 in the double auto-SCT arm completed the assigned treatment. At a median follow-up of 12.3 years from allo-SCT and 12.1 years from second auto-SCT, median overall survival (OS) was 11.4 in the allo-SCT arm and 3.9 years in the auto-SCT -arm (P = .007), whereas event-free survival was 3.6 and 1.5 years (P < .001), respectively. A subset of allo-SCT patients showed persistent molecular remission. Two-year cumulative incidence of chronic graft-versus-host disease was 67.2%. At 5 years, 39% of these patients were alive, disease-free, and off immunosuppression; 36.6% had relapsed and 12.2% were still on immunosuppression. Thirty-three of 58 patients (allo-SCT arm) and 39 of 46 (auto-SCT arm) relapsed at least once and were rescued with new drugs. In the allo-SCT arm, 2 patients in biochemical relapse did not reach clinical criteria for treatment. Overall 28 (90%) were treated with new drugs and 14 (45%) received donor lymphocyte infusions (DLIs). In 28 of 31 patients (90%) DLIs were given with new drugs. Median OS from first relapse was 7.5 years in the allo-SCT arm and 2 years in the auto-SCT arm (P = .01). Patients who received DLI showed significantly longer OS (hazard ratio, .38; P = .042) as compared with auto-SCT patients. This difference was slightly lower when only allo-SCT patients who did not receive DLIs were considered (hazard ratio, .56; P = .154). In summary, long term disease-free survival and survival outcomes after treating relapse with new drugs with or without DLIs were better in allo-SCT patients. PMID- 28987931 TI - Anti-inflammatory effect of glucose-lysine Maillard reaction products on intestinal inflammation model in vivo. AB - Inflammatory bowel diseases (IBDs) are chronic disorders that are characterized by intestinal epithelial inflammation and injury. Currently, the most employed therapies are antibiotics and anti-inflammatory drugs; however, the side effects limit long-term effectiveness. We evaluated the impact of glucose-lysine Maillard reaction products (Glc-Lys MRPs) on colitis, induced in rats by an administration of 5% dextran sulfate sodium (DSS) in drinking water. Glc-Lys MRPs ameliorate DSS induced colitis, as determined by a decrease in disease index activity, colon weight/length ratio, nitric oxide levels in serum, recovery of body weight loss, colon length and serum lysozyme levels. Furthermore, Glc-Lys MRPs increase the glutathione content and the activity of glutathione peroxidase, superoxide dismutase and catalase, and inhibit lipid peroxidation and myeloperoxidase activity in colon tissues. In particular, Glc-Lys MRPs suppress the mRNA level of the inflammatory cytokines and nuclear factor-kappaB in colon tissues. This study suggests the potential of Glc-Lys MRPs in preventing or treating IBDs. PMID- 28987932 TI - Ethyl pyruvate ameliorates inflammatory arthritis in mice. AB - OBJECTIVES: Ethyl pyruvate (EP) is the ethyl ester of pyruvate and has antioxidative and anti-inflammatory effects. This study aimed to evaluate the therapeutic effect of EP in inflammatory arthritis and to identify the underlying mechanisms. METHODS: Mice with collagen-induced arthritis (CIA) were treated with the vehicle control or EP at 20mg/kg, and clinical and histological analyses were performed on the animals. The differentiation of murine CD4+ T cells into T helper 17 (Th17) cells in the presence of EP was investigated in vitro. The effects of EP on osteoclastogenesis were determined by staining for tartrate resistant acid phosphatase, and measuring the mRNA levels of osteoclastogenesis related genes. The expression of high-mobility group box 1 (HMGB1) was evaluated after EP therapy using immunohistochemical staining and Western blotting. RESULTS: EP significantly improved the clinical and histological features of arthritis in CIA mice. EP suppressed the differentiation of CD4+ T cells into Th17 cells, and inhibited the expression of RORgammat. The generation of osteoclasts and osteoclastogenic markers from murine and human monocytes was significantly reduced in the presence of EP. The expression of HMGB1 in the synovium was significantly lower in CIA mice treated with EP, compared to control CIA mice. During osteoclastogenesis, HMGB1 release from monocytes was inhibited in the presence of EP. CONCLUSIONS: EP attenuated synovial inflammation and bone destruction in the experimental arthritis model through suppression of IL-17 and HMGB-1. The data suggests that EP could be a novel therapeutic agent for the treatment of inflammatory arthritis, such as rheumatoid arthritis. PMID- 28987933 TI - The influence of counseling on the mode of breech birth: A single-center observational prospective study in The Netherlands. AB - OBJECTIVE: women in the Netherlands, with a fetus in breech presentation, are thoroughly counseled to make an informed choice for the mode of delivery. The aim of this study was to assess the influence of counseling techniques on women's choices for the mode of delivery and subsequently to compare fetal and maternal outcomes of vaginal breech birth versus planned caesarean section. STUDY DESIGN: we performed an observational prospective study. Data on breech deliveries were prospectively collected. We used ANOVA to identify variables influencing women's choice for the mode of delivery. SETTING: the obstetric department of the Red Cross Hospital in Beverwijk, the Netherlands. PARTICIPANTS: women with a singleton gestation (>37 + 0 weeks) and a fetus in breech presentation were included. MEASUREMENTS AND FINDINGS: between January 2007 and December 2015 364 women were included. Counseling technique (p =<0.001) and maternal education (p = 0.046) were significantly associated with the choice of mode of delivery. Of all included women 33% (N = 119) opted for a vaginal breech delivery and 52% (N = 190) opted for a planned cesarean section. 15% (N = 55) were unexpected breeches. Of the planned vaginal delivery group 66% (N = 79) delivered vaginal, whereas 99.5% (N = 189) of the women in the planned cesarean section group underwent a planned cesarean section. There were no significant differences in maternal and neonatal outcomes. KEY CONCLUSIONS: women's choice on the mode of delivery and the eventual modus partus of fetuses in breech presentation is strongly influenced by the counseling technique. Vaginal breech birth in low-risk women is a safe option without long term morbidity in neonates. IMPLICATIONS FOR PRACTICE: counselors should be aware of their influence on women's choice for mode of delivery in breech presentation. Counseling should be done using evidence based information. PMID- 28987934 TI - Isothermal chemical denaturation of large proteins: Path-dependence and irreversibility. AB - State functions (e.g., DeltaG) are path independent and quantitatively describe the equilibrium states of a thermodynamic system. Isothermal chemical denaturation (ICD) is often used to extrapolate state function parameters for protein unfolding in native buffer conditions. The approach is prudent when the unfolding/refolding processes are path independent and reversible, but may lead to erroneous results if the processes are not reversible. The reversibility was demonstrated in several early studies for smaller proteins, but was assumed in some reports for large proteins with complex structures. In this work, the unfolding/refolding of several proteins were systematically studied using an automated ICD instrument. It is shown that: (i) the apparent unfolding mechanism and conformational stability of large proteins can be denaturant-dependent, (ii) equilibration times for large proteins are non-trivial and may introduce significant error into calculations of DeltaG, (iii) fluorescence emission spectroscopy may not correspond to other methods, such as circular dichroism, when used to measure protein unfolding, and (iv) irreversible unfolding and hysteresis can occur in the absence of aggregation. These results suggest that thorough confirmation of the state functions by, for example, performing refolding experiments or using additional denaturants, is needed when quantitatively studying the thermodynamics of protein unfolding using ICD. PMID- 28987936 TI - HMG-CoA synthase 2 drives brain metabolic reprogramming in cocaine exposure. AB - The brain is a high energy-consuming organ that typically utilizes glucose as the main energy source for cerebral activity. When glucose becomes scarce under conditions of stress, ketone bodies, such as beta-hydroxybutyrate, acetoacetate and acetone, become extremely important. Alterations in brain energy metabolism have been observed in psychostimulant abusers; however, the mode of brain metabolic programming in cocaine dependence remains largely unknown. Here, we profiled the metabolites and metabolic enzymes from brain nucleus accumbens (NAc) of mice exposed to cocaine. We found that cocaine modified energy metabolism and markedly activated ketogenesis pathway in the NAc. The expression of HMG-CoA synthase 2 (HMGCS2), a critical rate-limiting ketogenesis enzyme, was markedly up regulated. After switching metabolic pathways from ketogenesis to glycolysis through activation of glucokinase, cocaine-evoked metabolic reprogramming regained homeostasis, and the cocaine effect was attenuated. Importantly, both the pharmacological and genetic inhibition of HMGCS2 significantly suppressed cocaine-induced ketogenesis and behavior. In conclusion, cocaine induces a remarkable energy reprogramming in the NAc, which is characterized by HMGCS2 driven ketogenesis. Such effect may facilitate adaptations to cocaine-induced energy stress in the brain. Our findings establish an important link between drug induced energy reprogramming and cocaine effect, and may have implication in the treatment of cocaine addiction. PMID- 28987935 TI - In situ measurements of mitochondrial matrix enzyme activities using plasma and mitochondrial membrane permeabilization agents. AB - Activities of enzymes localized to the mitochondrial matrix of mammalian cells are often critical regulatory steps in cellular metabolism. As such, measurement of matrix enzyme activities in response to genetic modifications or drug interventions is often desired. However, measurements in intact cells are often hampered by the presence of other isozymes in the cytoplasm as well as the inability to deliver enzyme substrates across cellular membranes. Classic approaches to liberate matrix enzymes utilize harsh treatments that disrupt intracellular architecture or require significant starting material to allow mitochondrial isolation prior to sample extraction. We describe a method using permeabilization reagents for both the plasma and mitochondrial membranes to allow in situ measurement of matrix enzyme activities. It is applied to adherent cell monolayers in 96-well plates treated with perfringolysin O to permeabilize the plasma membrane and alamethicin to permeabilize the mitochondrial inner membrane. We present three examples validated with inhibitor sensitivity: (i) Complex I-mediated oxygen consumption driven by NADH, (ii) ATP hydrolysis by the F1FO complex measuring pH changes in an Agilent Seahorse XF Analyzer, and (iii) Mitochondrial glutaminase (GLS1) activity in a coupled reaction monitoring NADH fluorescence in a plate reader. PMID- 28987937 TI - Food for thought: Leptin regulation of hippocampal function and its role in Alzheimer's disease. AB - Accumulating evidence indicates that diet and body weight are important factors associated with Alzheimer's disease (AD), with a significant increase in AD risk linked to mid-life obesity, and weight loss frequently occurring in the early stages of AD. This has fuelled interest in the hormone leptin, as it is an important hypothalamic regulator of food intake and body weight, but leptin also markedly influences the functioning of the hippocampus; a key brain region that degenerates in AD. Increasing evidence indicates that leptin has cognitive enhancing properties as it facilitates the cellular events that underlie hippocampal-dependent learning and memory. However, significant reductions in leptin's capacity to regulate hippocampal synaptic function occurs with age and dysfunctions in the leptin system are associated with an increased risk of AD. Moreover, leptin is a potential novel target in AD as leptin treatment has beneficial effects in various models of AD. Here we summarise recent advances in leptin neurobiology with particular focus on regulation of hippocampal synaptic function by leptin and the implications of this for neurodegenerative disorders like AD. This article is part of the Special Issue entitled 'Metabolic Impairment as Risk Factors for Neurodegenerative Disorders.' PMID- 28987938 TI - TCB-2 [(7R)-3-bromo-2, 5-dimethoxy-bicyclo[4.2.0]octa-1,3,5-trien-7 yl]methanamine]: A hallucinogenic drug, a selective 5-HT2A receptor pharmacological tool, or none of the above? AB - The development of 5-HT2A receptor agonists has been considerably marginalized since the demonstration that the tryptaminergic drugs, LSD and psilocybin, or the phenylakylamine drugs, mescaline and DOI, exert their hallucinogenic properties via the stimulation of 5-HT2A receptors. Nonetheless, the ability of drugs to stimulate 5-HT2A receptors is not necessarily associated with psychedelic experience and the hallucinogenic properties are still not understood. Several studies have increased interest in stimulating 5-HT2A receptors in various CNS diseases. (7R)-3-bromo-2, 5-dimethoxy-bicyclo[4.2.0]octa-1,3,5-trien-7 yl]methanamine (TCB-2) which was synthetized in 2006 presents a high affinity with human and rat 5-HT2A receptors. Its main feature of interest is that it preferentially stimulates the phospholipase C and not phospholipase A2 pathway, which is at variance with several hallucinogenic drugs. Preference for TCB-2 has increased in preclinical studies and it exhibits subtle differences compared to DOI or LSD in some molecular, cellular and behavioral studies. The purpose of this review is to take a position on the use of TCB-2 as a pharmacological tool. A careful reading of the literature has revealed that the suspected hallucinogenic properties of TCB-2 cannot firmly be ascertained while its pharmacological profile is unknown and likely not selective at 5-HT2A receptors. This article is part of the Special Issue entitled 'Psychedelics: New Doors, Altered Perceptions'. PMID- 28987927 TI - Blood-brain barrier dysfunction and recovery after ischemic stroke. AB - The blood-brain barrier (BBB) plays a vital role in regulating the trafficking of fluid, solutes and cells at the blood-brain interface and maintaining the homeostatic microenvironment of the CNS. Under pathological conditions, such as ischemic stroke, the BBB can be disrupted, followed by the extravasation of blood components into the brain and compromise of normal neuronal function. This article reviews recent advances in our knowledge of the mechanisms underlying BBB dysfunction and recovery after ischemic stroke. CNS cells in the neurovascular unit, as well as blood-borne peripheral cells constantly modulate the BBB and influence its breakdown and repair after ischemic stroke. The involvement of stroke risk factors and comorbid conditions further complicate the pathogenesis of neurovascular injury by predisposing the BBB to anatomical and functional changes that can exacerbate BBB dysfunction. Emphasis is also given to the process of long-term structural and functional restoration of the BBB after ischemic injury. With the development of novel research tools, future research on the BBB is likely to reveal promising potential therapeutic targets for protecting the BBB and improving patient outcome after ischemic stroke. PMID- 28987939 TI - A hypothalamo-midbrain-medullary pathway involved in the inhibition of the respiratory chemoreflex response induced by potassium cyanide in rodents. AB - Recent studies have demonstrated that a mild stimulation of the dorsomedian nucleus of the hypothalamus (DMH), a defense area, induces the inhibition of the carotid chemoreflex tachypnea. DMH activation reduces the cardiac chemoreflex response via the dorsolateral part of the periaqueductal grey matter (dlPAG) and serotonin receptors (5-HT3 subtype) in the nucleus tractus solitarius (NTS). The objectives of this study were to assess whether dlPAG and subsequent NTS 5-HT3 receptors are involved in chemoreflex tachypnea inhibition during mild activation of the DMH. For this purpose, peripheral chemoreflex was activated with potassium cyanide (KCN, 40 MUg/rat, i.v.) during electrical and chemical minimal supra threshold (mild) stimulation of the dlPAG or DMH. In both situations, changes in respiratory frequency (RF) following KCN administration were reduced. Moreover, pharmacological blockade of the dlPAG prevented DMH-induced KCN tachypnea inhibition. Activation of NTS 5-HT3 receptors also reduced chemoreflex tachypnea in a dose-dependent manner. In addition, blockade of NTS 5-HT3 receptors with granisetron (2.5 but not 1.25 mM), or the use of mice lacking the 5-HT3a receptor (5-HT3a KO), prevented dlPAG-induced KCN reductions in RF. A respiratory hypothalamo-midbrain-medullary pathway (HMM) therefore plays a crucial role in the inhibition of the hyperventilatory response to carotid chemoreflex. PMID- 28987940 TI - MicroRNA-29a inhibits proliferation and induces apoptosis in rheumatoid arthritis fibroblast-like synoviocytes by repressing STAT3. AB - Rheumatoid arthritis-fibroblast-like synoviocytes (RA-FLS) with aberrant expression of microRNA (miRNA) have been reported to be involved in the initiation, progression, and perpetuation of rheumatoid arthritis (RA). In this study, we explored the biological function and underlying mechanism of microRNA 29a (miR-29a) in cultured RA-FLS from RA patients. The expression of miR-29a in serum, synovial tissues, and FLS from RA patients and health donors was detected by real-time quantitative RT-PCR (qRT-PCR). The effects of miR-29a on cell proliferation, apoptosis, and inflammatory cytokine levels in RA-FLS were also determined using Counting Assay Kit-8 (CCK-8), flow cytometry, and enzyme-linked immunosorbent assay (ELISA) respectively. Luciferase reporter assay was carried out to identify the target genes of miR-29a. We observed that expression of miR 29a was markedly downregulated in serum, synovial tissues and FLS of RA patients. miR-29a overexpression in RA-FLS significantly inhibited proliferation, promoted apoptosis, and suppressed expression of inflammatory cytokines. Signal transducer and activator of transcription 3 (STAT3) was identified to be a direct target of miR-29a in RA-FLS. miR-29a overexpression suppressed the expression of STAT3, as well as phosphorylated STAT3(p-STAT3) and its downstream targets protein (Cyclin D1 and Bcl-2). In addition, the levels of miR-29a were inversely correlated with that of STAT3 in synovial tissues. Rescue experiments showed that overexpression of STAT3 effectively reversed the effect of miR-29a on proliferation and apoptosis in RA-FLS. These data indicate that miR-29a inhibits proliferation and induces apoptosis in RA-FLS by targeting STAT3, suggesting that promoting miR-29a expression may yield therapeutic benefits in the treatment of RA. PMID- 28987942 TI - miR-205 regulation of ICT1 has an oncogenic potential via promoting the migration and invasion of gastric cancer cells. AB - Immature colon carcinoma transcript-1 (ICT1) is a newly identified oncogene, which regulates mobility, apoptosis, cell cycle progression and proliferation of cancer cells. Nevertheless, the role of ICT1 and its clinical significance in gastric cancer (GC) is largely uncovered. Here, we found that ICT1 displayed higher expression in GC tissues compared to corresponding tumor-adjacent tissues. Further investigation confirmed ICT1 overexpression in GC cell lines. Clinical data disclosed that high ICT1 expression correlated with distant metastasis and advanced tumor-node-metastasis (TNM) stage. The Cancer Genome Atlas (TCGA) data further demonstrated that GC tissues with metastasis showed a significant higher level of ICT1 compared to those without metastasis. Furthermore, ICT1 overexpression notably predicted poor prognosis of GC patients. Functionally, we demonstrated that ICT1 knockdown suppressed invasion and migration of MGC-803 and BGC-823 cells in vitro. ICT1 overexpression promoted the mobility of SGC-7901 cells. Mechanistically, microRNA-205 (miR-205) was recognized as a direct down regulator and inversely modulated ICT1 abundance in GC cells. miR-205 expression was down-regulated and negatively associated with ICT1 level in GC tissues. Underexpression of miR-205 indicated an obvious shorter survival of GC patients. miR-205 overexpression inhibited migration and invasion of MGC-803 cells, while these inhibitory effects were reversed by ICT1 restoration. Taken together, we have the earliest evidence that miR-205 regulation of ICT1 functions as an oncogene and prognostic biomarker in GC. PMID- 28987941 TI - Study of the non-clinical healing activities of the extract and gel of Portulaca pilosa L. in skin wounds in wistar rats: A preliminary study. AB - INTRODUCTION: Portulaca pilosa L., belonging to the family Portulacaceae, is a common herbaceous plant in the Americas and in the Amazon, is popularly known as love-grown and is traditionally used as an aid in the treatment of burns, buds, insect bites and wound healing. This study aims to evaluate the non-clinical topical healing activity of the P. pilosa gel (GPP) and the propyleneglycol extract of P. pilosa (EPP) in Wistar rats. METHODS: For the healing activity, wistar rats were divided into the following groups: negative control (GVE - vehicle, 150mg/kg), positive control (Fibrinase(r)- FIB, 100U/kg), Portulaca pilosa gel 10%, (GPP, 150mg/kg), and propylenglycollic extract of Portulaca pilosa (EPP, 150 mg/kg), which were submitted to a surgical procedure to obtain the wounds, and were treated topically for 7days. After treatment, the treated area was removed and a histopathological analysis was performed. RESULTS: The EPP when analyzed in HPLC was able to identify the presence of gallic acid. EPP significantly modulated the tissue inflammatory response, presenting low number of inflammatory cells in the histopathological study. Treatment with EPP and GPP significantly stimulated angiogenesis and this response was superior to the fibrinase(r) group. Treatment with EPP and GPP significantly stimulated the proliferation of fibroblasts. The groups treated with EPP and GPP presented an organization pattern of the epidermis and dermis better than the control group, with a mild inflammatory process, with fibroblast proliferation and increased formation of collagen fibers. CONCLUSION: Thus, from the results obtained it can be suggested that the phytochemical marker of the P. pilosa species for healing activity is gallic acid and, together with the macroscopic and microscopic findings triggered by the topical applications of EPP and GPP, it can be concluded that this plant species has topical healing activity, with great potential for use, since this pharmacological action is associated with a possible topical anti-inflammatory activity. PMID- 28987943 TI - A standardized extract of Butea monosperma (Lam.) flowers suppresses the IL-1beta induced expression of IL-6 and matrix-metalloproteases by activating autophagy in human osteoarthritis chondrocytes. AB - BACKGROUND/OBJECTIVE: Osteoarthritis (OA) is a leading cause of joint dysfunction, disability and poor quality of life in the affected population. The underlying mechanism of joint dysfunction involves increased oxidative stress, inflammation, high levels of cartilage extracellular matrix degrading proteases and decline in autophagy-a mechanism of cellular defense. There is no disease modifying therapies currently available for OA. Different parts of the Butea monosperma (Lam.) plant have widely been used in the traditional Indian Ayurvedic medicine system for the treatment of various human diseases including inflammatory conditions. Here we studied the chondroprotective effect of hydromethanolic extract of Butea monosperma (Lam.) flowers (BME) standardized to the concentration of Butein on human OA chondrocytes stimulated with IL-1beta. METHODS: The hydromethanolic extract of Butea monosperma (Lam.) (BME) was prepared with 70% methanol-water mixer using Soxhlet. Chondrocytes viability after BME treatment was measured by MTT assay. Gene expression levels were determined by quantitative polymerase chain reaction (qPCR) using TaqMan assays and immunoblotting with specific antibodies. Autophagy activation was determined by measuring the levels of microtubule associated protein 1 light chain 3-II (LC3 II) by immunoblotting and visualization of autophagosomes by transmission electron and confocal microscopy. RESULTS: BME was non-toxic to the OA chondrocytes at the doses employed and suppressed the IL-1beta induced expression of inerleukin-6 (IL-6) and matrix metalloprotease-3 (MMP-3), MMP-9 and MMP-13. BME enhanced autophagy in chondrocytes as determined by measuring the levels of LC3-II by immunoblotting and increased number of autophagosomes in BME treated chondrocytes by transmission electron microscopy and confocal microscopy. BME upregulated the expression of several autophagy related genes and increased the autophagy flux in human OA chondrocytes under pathological conditions. Further analysis revealed that BME activated autophagy in chondrocytes via inhibition of mammalian target of rapamycin (mTOR) pathway. Of importance is our finding that BME-mediated suppression of IL-1beta induced expression of IL-6, MMP-3, -9, and 13 was autophagy dependent and was abrogated by inhibition of autophagy. CONCLUSION: The above results show that the Butea monosperma (Lam.) extract has strong potential to activate autophagy and suppress IL-1beta induced expression of IL-6 and MMP-3, -9 and -13 in human OA chondrocytes. This study shows that BME or compounds derived from BME can be developed as safe and effective chondroprotective agent(s) that function by activating autophagy to suppress the expression of inflammatory and catabolic factors associated with OA pathogenesis. PMID- 28987944 TI - MiR-140-5p inhibits synovial fibroblasts proliferation and inflammatory cytokines secretion through targeting TLR4. AB - OBJECTIVES: This study was aimed to investigate the effects of miR-140-5p on the proliferation and inflammatory cytokines secretion of rheumatoid arthritis synovial fibroblasts (RASFs). METHODS: Synovial tissue samples from 23 rheumatoid arthritis (RA) patients and 18 normal synovial tissue samples were collected. The RASFs were isolated and cultured. Then, miR-140-5p and TLR4 expression in both synovial tissue and RASFs were detected using the quantitative real-time PCR (qPCR) and western blot. Dual luciferase reporter gene assay was employed to evaluate the interaction between miR-140-5p and 3'UTR of TLR4. Western blotting and qPCR were used to examine TLR2 expression after upregulation or downregulation of miR-140-5p in RASFs. After RASFs co-infected with TLR4 overexpression lentivirus and lentivirus containing miR-140-5p or miR-control respectively, the cellular proliferation and secretion of IL-6 and IL-8 level were detected through the MTS assay and enzyme-linked immunosorbent assay, respectively. RESULTS: MiR-140-5p was significantly down-regulated, and TLR4 was significantly up-regulated in synovial tissue samples from 23 RA patients and RASFs. Dual luciferase activity assay showed that miR-140-5p could specifically bind to the 3'UTR of TLR4. Down-regulation or up-regulation of miR-140-5p not only significantly increased or decreased the expression of TLR4, but also could promote or inhibit RASF proliferation and secretion of IL-6, and IL-8 in RASFs. Furthermore, overexpression of TLR4 can reverse the inhibitory effects of miR-140 5p on proliferation and inflammatory cytokines release of RASFs. CONCLUSIONS: MiR 140-5p could inhibit the proliferation and secretion of IL-6 and IL-8 through regulation of TLR4 expression. PMID- 28987945 TI - Simvastatin exerts antifibrotic effect and potentiates the antischistosomal effects of praziquantel in a murine model: Role of IL10. AB - Previous studies on simvastatin use in experimental schistosomiasis in mice did not provide a full explanation of its mechanism as antischisome. In this study, we tried to find out the role of IL-10 in the mechanism of action of simvastatin. We used 50 clear mice. Ten were used as normal not treated while 40 were infected with shistosome mansoni then divided into 4 groups; 3 treated groups by praziquantel, simvastatin and combined (praziquantel plus simvastatin) respectively and one group non-treated. The simvastatin treated group showed shortening and loss of the tubercles and disappearance of the spines with swelling and twisted shape of the worms. In addition, it also showed mitigation of ovideposition activity of the worms in the liver and reduction of the fibrous component of the liver granuloma producing a protective effect on the liver. This effect was associated with lowering of IL-10. This may explain the role of IL-10 in the protective effect of simvastatin. Combination of treatment with simvastatin plus praziquantel produced more significant effects in different parameters compared with praziquantel treated group. We recommend using simvastatin as add on therapy to standard antischistosomal therapy, praziquantel. Both drugs affect the worm motility and sucker activity and the ova deposition. Simvastatin has an additional pleiotropic effect halting inflammation and decreasing fibrosis due to increasing IL-10 leading to a hepatoprotective effect. Further clinical studies are needed to further validate these findings. PMID- 28987946 TI - Tetrahydroxy stilbene glycoside (TSG) antagonizes Abeta-induced hippocampal neuron injury by suppressing mitochondrial dysfunction via Nrf2-dependent HO-1 pathway. AB - Amyloid-beta peptide (Abeta) ranks as a pivotal cause of Alzheimer's disease (AD), a common devastating dementia form in elderly. Recent research corroborated the beneficial roles of tetrahydroxystilbene glucoside (TSG) in alleviating the learning and memory of AD model and aged mice. Unfortunately, the underlying mechanism remains poorly elucidated. Here, treatment with non-toxic TSG dose dependently antagonized Abeta-induced cytotoxic death in hippocampal neuronal cells by increasing cell viability and decreasing cell apoptosis. Furthermore, TSG also alleviated cell oxidative stress injury in response to Abeta by attenuating lactate dehydrogenase (LDH) release, ROS levels and MDA leakage. Importantly, TSG administration abrogated Abeta-triggered loss of mitochondrial membrane potential (Deltaym), release of cytochrome c from mitochondrial to cytosol, increase in caspase-3 activity and pro-apoptotic protein Bax, and decrease in Bcl-2 protein, indicating that TSG could rescue mitochondrial dysfunctions of neuron cells under adverse Abeta condition. Subsequently, TSG induced the activation of Nrf2-HO-1 pathway. Importantly, blocking this pathway by si-Nrf2 transfection or HO-1 antagonist ZnPP notably muted the cytoprotective effects of TSG on neuronal cell cytotoxic injury upon Abeta stimulation. Together, this research substantiated a new mechanism that TSG protectively antagonized Abeta-induced hippocampal neuronal cell damage by restoring mitochondrial function via Nrf2-HO-1 pathway, implying a promising candidate against neurodegenerative diseases including AD. PMID- 28987947 TI - MiR-206 inhibits Head and neck squamous cell carcinoma cell progression by targeting HDAC6 via PTEN/AKT/mTOR pathway. AB - As a kind of endogenous noncoding small RNA, microRNA (miRNA) plays important roles of regulation to various physiological functions, while its affections on senescence of human Head and neck squamous cell carcinoma (HNSCC) are still unknown. The objective of this study was to investigate the effect of miR-206 in HNSCC tissues, adjacent normal tissues and cell lines, and explore its biological functions in HNSCC. In our study, the level of miR-206 in HNSCC tissues and adjacent normal tissues was detected via real-time qPCR. The effect of miR-206 on cell proliferation was tested by MTT assay, colony formation and cell cycle assays. In order to explore the effect of miR-206 on HNSCC cell migration and invasion, we performed wound healing assays and transwell assays. Luciferase reporter assays were designed to identify the interaction between 3'UTR of HDAC6 and miR-206. The level of signaling pathway-related proteins was determined by western blot. The expression of miR-206 was found to be observably decreased in HNSCC tissues and cell lines through real time-PCR. Restoration of miR-206 weaked cell proliferation, invasion and migration in HNSCC cells and the cell cycle was arrest in S phase. Further explores have shown that miR-206 could inhibit HNSCC cells proliferation by targeting the HDAC6 via PTEN/AKT/mTOR pathway. Taken together, our results demonstrated that miR-206 plays a critical role in HNSCC progression by targeting HDAC6 via PTEN/AKT/mTOR pathway, which might be a potential target for diagnostic and therapeutic in HNSCC. PMID- 28987948 TI - MiR-146a functions as a small silent player in gastric cancer. AB - Gastric cancer is responsible for approximately one million annual deaths worldwide. Recently, the important roles of miRNAs as vital factors in malignancy processes such as metastasis have identified. They involve in the regulation of different biological procedures such as proliferation, invasion, metastasis and cell survival. MiR-146a has an aberrant expression in different tumors and has different expressions in the gastric cancer cell lines. This microRNA can act as a tumor suppressor and/or oncogene in gastric cancer related cases. Most of the studies have confirmed that miR-146a is downregulated in human gastric cancer cell lines and tissues, significantly and that it has tumor suppressor effects in gastric cancers. On the other hand, the role of miR-146a as an oncogene has been studied in an in-vitro experiment and results showed that over- an expression of miR-146a in gastric cancer tissues inhibits apoptosis and improves cell proliferation of gastric cancer cell. MiR-146a also has been a candidate for diagnosis and prognosis in gastric cancer cases. In this review, we focus on the important roles of miR-146a in tumor genesis of gastric tissues, emphasizing on the involvement of this microRNA in diagnosis, prognosis, chemotherapy response and finally, potential therapeutic applications as an anticancer agent in inhibition of gastric cancer cell metastasis and invasion. PMID- 28987949 TI - Zingiberis rhizoma mediated enhancement of the pharmacological effect of aconiti lateralis radix praeparata against acute heart failure and the underlying biological mechanisms. AB - Aconiti Lateralis Radix Praeparata (Fuzi), a type of Chinese materia medica, has been used to treat acute and chronic heart failure (HF) in traditional Chinese medicine and has been proven in numerous animal studies. It is also well-known that Zingiberis Rhizoma (Ganjiang) is ineffective in the treatment of HF, but it can enhance the anti-HF effect of Fuzi. However, the mechanism underlying this compatibility is still not well investigated. To investigate this mechanism, a model of acute heart failure (AHF) in SD rats induced by propafenone hydrochloride was established in this study. After oral treatments of Ganjiang, Fuzi or a combination of the two drugs in rats with AHF, heart function [e.g., heart rate (HR) and the maximal rising and declining rate of left ventricle pressure (+/-dp/dtmax)] and serum indicators [e.g., brain natriuretic peptide (BNP), lactate dehydrogenase (LDH) and creatine kinase (CK)] were measured, and histopathological analysis of the heart was also performed. The biological mechanisms were further explored by measuring the protein expression level of the mitochondrial respiration chain complex (MRCC1-4) and the mRNA and protein expression levels of mitochondrial Ca2+ uniporter (MCU) and its upstream proteins, mitochondrial Ca2+ uniporter 1 and mitochondrial Ca2+ uniporter 2 (MICU1-2). The expression levels of key enzymes downstream of the tricarboxylic acid cycle, including pyruvate dehydrogenase (PDH), malate dehydrogenase (MDH) and nicotinamide nucleotide transhydrogenase (NNT), were also measured. As a result, Ganjiang enhanced the therapeutic effect of Fuzi on AHF by raising the HR and +/-dp/dtmax; decreasing the serum levels of BNP, LDH and CK; and alleviating histological damage of the myocardial tissue when compared to the treatments of Ganjiang or Fuzi alone. In conclusion, there was an enhancing effect of Ganjiang on the anti-AHF function of Fuzi treatment, and the potential mechanism of this effect may be related to the mitochondrial energy metabolism pathway mediated by MCU. PMID- 28987950 TI - Antiviral activity of a polysaccharide from Laminaria japonica against enterovirus 71. AB - This in vitro study investigated the antiviral activity of an acidic polysaccharide from Laminaria japonica against enterovirus 71 (EV71) as well as its mechanism of action. The LJ04 polysaccharide was purified from Laminaria japonica by affinity chromatography. To investigate its antiviral activity, an MTT assay, q-PCR, immunofluorescent staining and western-blot analysis were performed. To define its mechanism of action, ELISA, q-PCR and flow cytometry were conducted. LJ04 had a low EC50, high CC50 and high SI. LJ04 inhibited not only JN200804, but also JN200803 in RD cells, and viral proliferation was strongly inhibited, whereas LJ04 suppressed viral-induced apoptosis as detected by flow cytometry. In conclusion, LJ04 was found to have robust antiviral activity by inhibiting apoptosis and inducing IFN-beta expression. Our findings indicate that LJ04 is a good candidate for the treatment of EV71. PMID- 28987951 TI - Taurine alleviates malathion induced lipid peroxidation, oxidative stress, and proinflammatory cytokine gene expressions in rats. AB - The present study was considered to evaluate the protective effect of taurine on malathion-induced toxicity in rats. Totally, 48 male rats were divided into 6 equal groups: 0.5ml physiological salt solution was given orally to control rats. 0.5ml corn oil was given orally to rats in corn oil group. Malathion at dose of 27mg/kg (1/50 of LD50) was dissolved in 0.5ml corn oil and given to orally rats in malathion group. The other groups; malathion (27mg/kg) and taurine (dissolved in 0.5ml physiological salt solution) at dose of 50, 100, and 200mg/kg were given orally to rats for 30days, respectively. Malathion treatment decreased acetylcholinesterase levels in serum (30%) and liver (25%) compared to the control group. Malathion resulted in a significant increase in malondialdehyde levels whereas decreased glutathione levels, superoxide dismutase, and catalase activities in rats. Also, IF-gamma, IL1-beta, TNF-alpha, and NFKB mRNA expression levels were found to be increased 5, 1.7, 2.3, and 2.5 fold in malathion treated rats compared to control, respectively. However, treatment of taurine, in a dose dependent manner, resulted in a reversal of malathion-induced lipid peroxidation, antioxidant enzyme activities, and mRNA expression levels of proinflammatory cytokines. Moreover, taurine demonstrated preventive action against malathion induced histopathological changes in rat tissues. In conclusion, taurine exhibited a protective effect in rats against malathion-induced lipid peroxidation, besides it ameliorated antioxidant status, decreased mRNA expression levels of proinflammatory cytokine and repaired rat tissues. PMID- 28987952 TI - Physicochemical properties and cytotoxicity of cysteine-functionalized silver nanoparticles. AB - The preparation of stable cysteine-capped silver nanoparticles (AgNPs), via the reduction of silver ions with sodium borohydride and modification of formed nanoparticles by l-cysteine, was developed. The micrographs from transmission electron microscopy (TEM) revealed that the spherical AgNPs exhibited an average size equal to 22+/-4nm. Surface enhanced Raman spectroscopy (SERS) and inductively coupled plasma optical emission spectrometry (ICP-OES) confirmed a chemisorption of cysteine molecules on the AgNPs. Additionally, dynamic light scattering (DLS) measurements showed that the AgNPs were stable for ionic strength lower than 5*10-3molL-1 and at 6.8eEF-1>UBC>B2M>ACTB>SDHA for dorsal root ganglia and ACTB>SDHA>UBC>B2M>GAPDH>eEF-1 for spinal cord samples. Expression stability estimates were verified by BestKeeper and NormFinder analysis. Expression stability varied between genes within and between tissues. Validation of most stably expressed reference genes was performed by normalisation of calcitonin gene related polypeptide beta (CALCB). The results show similar patterns of CALCB expression when the best reference genes selected by all three programs were used. GAPDH, eEF-1 and UBC are suitable reference genes for porcine dorsal root ganglia samples, whereas ACTB, SDHA and UBC are more appropriate for spinal cord samples. PMID- 28987957 TI - The first report of cases of pet dogs with naturally occurring cancer treated with the antitumor peptide CIGB-552. AB - The absence of an effective therapy against human solid tumors has fostered the development of promising antineoplastic therapeutic candidates, as the CIGB-552 peptide. This synthetic peptide has shown to be effective in reducing tumor size and increasing the lifespan in tumor-bearing mice. Therefore, this work was aimed to explore the safety profile and preliminary assessment of antitumor activity of the CIGB-552 peptide therapeutic candidate in a small population of dogs (n=9) having malignant spontaneously-arising solid tumors. The peptide was administered by subcutaneous (s.c.) route, at three dosage levels (0.075, 0.15 and 0.3mg/kg). The results showed no dose-limiting toxicities in any dogs. The antitumor activity observed in dogs receiving CIGB-552 was associated with the reduction in the tumor volume. Given the antitumor effects of CIGB-552 as mediated by COMMD1 protein, which function is highly conserved among eukaryotic organisms, and the similarities of canine and human types of cancer with respect to tumor biology, it is likely that CIGB-552 could demonstrate comparable anti-cancer activity in human patients. Synthetic peptide, COMMD1, Tumor, Dog, CIGB-552. PMID- 28987958 TI - Study of the association of atmospheric temperature and relative humidity with bulk tank milk somatic cell count in dairy herds using Generalized additive mixed models. AB - Elevated bulk tank milk somatic cell count (BMSCC) has a negative impact on milk production, milk quality, and animal health. Seasonal increases in herd level somatic cell count (SCC) are commonly associated with elevated environmental temperature and humidity. The Temperature Humidity Index (THI) has been developed to measure general environmental stress in dairy cattle; however, additional work is needed to determine a specific effect of the heat stress index on herd-level SCC. Generalized Additive Model methods were used for a flexible exploration of the relationships between daily temperature, relative humidity, and bulk milk somatic cell count. The data consist of BMSCC and meteorological recordings collected between March 2009 and October 2011 of 10 dairy farms. The results indicate that, an average increase of 0.16% of BMSCC is expected for an increase of 1 degrees C degree of temperature. A complex relationship was found for relative humidity. For example, increase of 0.099%, 0.037% and 0.020% are expected in correspondence to an increase of relative humidity from 50% to 51%, 80% to 81%; and 90% to 91%, respectively. Using this model, it will be possible to provide evidence-based advice to dairy farmers for the use of THI control charts created on the basis of our statistical model. PMID- 28987959 TI - Reanalysis of the role of pronase treatment of B cells in the flow cytometric crossmatch assay: Fc receptor is not the primary target. AB - Pronase, a mixture of nonspecific bacterial proteases, is used to pretreat human lymphocytes to prevent false-positive B cell results in the flow cytometric crossmatch (FCXM) assay. The target of pronase has been reported to be B cell expressed Fc receptors, which nonspecifically bind IgG. As pronase use in FCXM can induce other complications, including degradation of HLA leading to inappropriate FCXM results, and false-positive T cell results when testing serum from HIV-positive patients, we tested whether specifically blocking Fc receptor CD32 could replace pronase. Anti-CD32 mAb 6C4 was superior to pronase for blocking binding of aggregated IgG to B cells. However, 6C4 was unable to replace pronase in clinical FCXM, as it did not prevent false-positive B cell FCXM results, or enhance sensitivity of the assay. We conclude that the functional targets of pronase in the FCXM assay are poorly understood, and that B cell expressed Fc receptor plays an insignificant role. PMID- 28987960 TI - Frequencies of gene variant CCR5-Delta32 in 87 countries based on next-generation sequencing of 1.3 million individuals sampled from 3 national DKMS donor centers. AB - Homozygous carriers of CCR5-Delta32, a gene variant of CC-type chemokine receptor 5 (CCR5), are highly resistant to infections with human immunodeficiency virus type 1 (HIV-1) and therefore preferred stem cell donors for HIV-infected patients. We analyzed CCR5 typing data of 1,333,035 potential hematopoietic stem cell donors enlisted with three national DKMS donor centers. Allele and genotype frequencies were determined for 87 countries of origin as self-assessed by the donors. CCR5-Delta32 allele frequencies ranged from 16.4% in the Norwegian sample to 0 in donors from Ethiopia. The highest CCR5-Delta32/Delta32 genotype frequency was found in the sample from the Faroe Islands (2.3%), whereas in 27 samples, predominantly of donors from Africa, Asia and South America, none of the individuals carried this genotype. The characteristic CCR5-Delta32 allele frequency decline from Northern to Southeastern Eurasia supports findings of earlier studies. With available HLA haplotype frequency information for the patient's ethnicity, our data allows upfront estimation of the probability that an HLA-matched donor with CCR5-Delta32/Delta32 genotype can be found for a patient in need of hematopoietic stem cell transplantation. PMID- 28987961 TI - The effect of genetic variants affecting NK cell function on cardiovascular health and the burden of CMV. AB - Renal transplant recipients (RTR) display high burdens of cytomegalovirus (CMV) and accelerated cardiovascular change. NK cells can control CMV and may contribute to vascular pathologies. Polymorphisms in genes encoding the inhibitory receptor LILRB1 and its ligand HLA-G, and the activating receptor NKG2C may illuminate the role of NK cells in vascular health and CMV immunity. We assessed 81 healthy adults and 82 RTR >2 years after transplantation. RTR had higher humoral and T-cell responses to CMV, and impaired vascular health. A 14bp indel in HLA-G associated with increased flow-mediated dilatation of the brachial artery. The T allele of LILRB1 rs1061680 associated with increased carotid intimal media thickness (cIMT) in RTR and controls. A 16 kb deletion encompassing the NKG2C gene associated with lower cIMT values and higher humoral and T-cell responses to CMV. Hence all polymorphisms tested had small but discernable effects on vascular health. The NKG2C deletion may act via CMV. PMID- 28987962 TI - Association of cytokine gene polymorphisms with the complications of allogeneic haematopoietic stem cell transplantation. AB - The purpose of our study was to confirm the prevalence of the association between single nucleotide polymorphisms present in genes encoding cytokines and the complications occurring after haematopoietic stem cell transplantation (HSCT). 108 recipients and 81 donors were typed for TNF-alpha (-308), TGF-beta1 (codon 10, 25), IL-10 (-1082, -819, -592), IL-6 (-174) and INF-gamma (+874). Our studies have shown a tendency toward association between the occurrence of acute form of graft versus host disease (aGVHD) and IL-6 genotype. Homozygote C/C was less likely to develop aGVHD (p=0,09). Genotype GCC/ATA in IL-10 recipient gene alone had protective effect against the occurrence of aGVHD (p=0,01). Furthermore, GCC/ATA protected the host against developing the disease in the clinically relevant grades (II-IV) (p=0,03). In addition, the recipient's T/T G/G genotype (TGF-beta1) predisposed to the development of both acute (p=0,06 - trend) and chronic (p=0,04) GVHD and also severe aGVHD (p=0,004). We also observed a statistically significant association between the genotype of recipient and the risk of infection - the protective function of the G/C IL-6 in the bloodstream infections (p=0,001). Our results suggest that IL-6, IL-10 and TGF-beta1 genotypes of recipient are the most associated with the risk of complications after HSCT. PMID- 28987963 TI - Improving cancer patient emergency room utilization: A New Jersey state assessment. AB - INTRODUCTION: Due to its increasing incidence and its major contribution to healthcare costs, cancer is a major public health problem in the United States. The impact across different services is not well documented and utilization of emergency departments (ED) by cancer patients is not well characterized. The aim of our study was to identify factors that can be addressed to improve the appropriate delivery of quality cancer care thereby reducing ED utilization, decreasing hospitalizations and reducing the related healthcare costs. METHODS: The New Jersey State Inpatient and Emergency Department Databases were used to identify the primary outcome variables; patient disposition and readmission rates. The independent variables were demographics, payer and clinical characteristics. Multivariable unconditional logistic regression models using clinical and demographic data were used to predict hospital admission or emergency department return. RESULTS: A total of 37,080 emergency department visits were cancer related with the most common diagnosis attributed to lung cancer (30.0%) and the most common presentation was pain. The disposition of patients who visit the ED due to cancer related issues is significantly affected by the factors of race (African American OR=0.6, p value=0.02 and Hispanic OR=0.5, p value=0.02, respectively), age aged 65 to 75years (SNF/ICF OR 2.35, p value=0.00 and Home Healthcare Service OR 5.15, p value=0.01, respectively), number of diagnoses (OR 1.26, p value=0.00), insurance payer (SNF/ICF OR 2.2, p value=0.02 and Home Healthcare Services OR 2.85, p value=0.07, respectively) and type of cancer (breast OR 0.54, p value=0.01, prostate OR 0.56, p value=0.01, uterine OR 0.37, p value=0.02, and other OR 0.62, p value=0.05, respectively). In addition, comorbidities increased the likelihood of death, being transferred to SNF/ICF, or utilization of home healthcare services (OR 1.6, p value=0.00, OR 1.18, p value=0.00, and OR 1.16, p value=0.04, respectively). Readmission is significantly affected by race (American Americans OR 0.41, standard error 0.08, p value=0.001 and Hispanics OR 0.29, standard error 0.11, p value=0.01, respectively), income (Quartile 2 OR 0.98, standard error 0.14, p value 0.01, Quartile 3 OR 1.07, standard error 0.13, p value 0.01, and Quartile 4 OR 0.88, standard error 0.12, p value 0.01, respectively), and type of cancer (prostate OR 0.25, standard error 0.09, p value=0.001). CONCLUSION: Web based symptom questionnaires, patient navigators, end of life nursing and clinical cancer pathways can identify, guide and prompt early initiation of treat before progression of symptoms in cancer patients most likely to visit the ED. Thus, improving cancer patient satisfaction, outcomes and reduce health care costs. PMID- 28987964 TI - Meta-analysis of the clinicopathological characteristics and peri-operative outcomes of colorectal cancer in obese patients. AB - BACKGROUND: The effect of obesity on the clinicopathological characteristics of colorectal cancer (CRC) has not been clearly characterized. This meta-analysis assesses the pathological and perioperative outcomes of obese patients undergoing surgical resection for CRC. METHODS: Meta-analysis was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Databases were searched for studies reporting outcomes for obese and non-obese patients undergoing primary CRC resection, based on body-mass index measurement. Results were reported as mean differences or pooled odds ratios (OR) with 95% confidence intervals (95% CI). RESULTS: A total of 2183 citations were reviewed; 29 studies comprising 56,293 patients were ultimately included in the analysis, with an obesity rate of 19.3%. Obese patients with colorectal cancer were more often female (OR 1.2, 95% CI 1.1-1.2, p<0.001) but there was no difference in the proportion of rectal cancers, T4 tumours, tumour differentiation or margin positivity. Obese patients were significantly more likely to have lymph node metastases (OR 1.2, 95% CI 1.1-1.2, p<0.001), have a lower nodal yield, were associated with a longer duration of surgery, more blood loss and conversions to open surgery (OR 2.6, 95% CI 1.6-4.0, p<0.001) but with no difference in length of stay or post-operative mortality. CONCLUSION: This meta-analysis demonstrates that obese patients undergoing resection for CRC are more likely to have node positive disease, longer surgery and higher failure rates of minimally invasive approaches. The challenges of colorectal cancer resection in obese patients are emphasized. PMID- 28987965 TI - Emerging targets in cancer immunotherapy. AB - The first generation of immune checkpoint inhibitors (anti-CTLA-4 and anti-PD 1/PD-L1) targeted natural immune homeostasis pathways, co-opted by cancers, to drive anti-tumor immune responses. These agents led to unprecedented results in patients with previously incurable metastatic disease and may become first-line therapies for some advanced cancers. However, these agents are efficacious in only a minority of patients. Newer strategies are becoming available that target additional immunomodulatory mechanisms to activate patients' own anti-tumor immune responses. Herein, we present a succinct summary of emerging immune targets with reported pre-clinical efficacy that have progressed to active investigation in clinical trials. These emerging targets include co-inhibitory and co-stimulatory markers of the innate and adaptive immune system. In this review, we discuss: 1) T lymphocyte markers: Lymphocyte Activation Gene 3 [LAG 3], T-cell Immunoglobulin- and Mucin-domain-containing molecule 3 [TIM-3], V domain containing Ig Suppressor of T cell Activation [VISTA], T cell ImmunoGlobulin and ITIM domain [TIGIT], B7-H3, Inducible T-cell Co-stimulator [ICOS/ICOS-L], CD27/CD70, and Glucocorticoid-Induced TNF Receptor [GITR]; 2) macrophage markers: CD47/Signal-Regulatory Protein alpha [SIRPalpha] and Indoleamine-2,3-Dioxygenase [IDO]; and 3) natural killer cell markers: CD94/NKG2A and the Killer Immunoglobulin-like receptor [KIR] family. Finally, we briefly highlight combination strategies and potential biomarkers of response and resistance to these cancer immunotherapies. PMID- 28987966 TI - How available to European children and young people with cerebral palsy are features of their environment that they need? AB - BACKGROUND: The UN Convention on the Rights of Persons with Disabilities requires accessibility to the physical and social environments. However, individuals with cerebral palsy (CP) have many difficulties in accessing the environment they need for functional independence and social inclusion. AIMS: To examine the availability of environmental features which children with CP need for optimal participation, and whether availability changed for them between ages 8-12 and 13 17 years. METHODS: The sample is the 594 children with CP, born 31/07/1991 01/04/1997, who took part in the SPARCLE study at age 8-12 (SPARCLE 1) and again at 13-17 years (SPARCLE 2). Participants were randomly sampled from population registers of children with CP in eight European regions; one further region recruited from multiple sources. Data about environment were captured with the European Child Environment Questionnaire (60 items). Differences in availability of environmental features between childhood and adolescence were assessed using McNemar's test; differences between regions were assessed by ranking regions. Differences in availability between regions were assessed by ranking regions. RESULTS: For seven environmental features significantly (p<0.01) fewer individuals needed the feature in SPARCLE 2 than in SPARCLE 1, whilst for two features more individuals needed the feature. Nine features in SPARCLE 1 and six features in SPARCLE 2 were available to less than half the participants who needed them. Eight features showed significantly (p<0.01) higher availability in SPARCLE 2 than in SPARCLE 1 (enlarged rooms, adapted toilet, modified kitchen and hoists at home, adapted toilets and lifts at school, an adequate vehicle, grants for home modifications) while none showed significantly lower availability. The relative rankings of the better and less good regions persisted from the age 8 12year age group to the 13-17year age group. CONCLUSIONS: Needed environmental features are unavailable to many children at ages 8-12 and 13-17 years. This lack of availability is more pronounced in some regions than others, which probably results from their policy, legislative and statutory frameworks. PMID- 28987967 TI - The bouba-kiki effect and its relation to the Autism Quotient (AQ) in autistic adolescents. AB - The bouba-kiki effect refers to the correspondence between arbitrary visual and auditory stimuli. Previous studies indicate ASD persons' reduced bouba-kiki effect compared to controls. This study examines the relation between ASD symptomology and performance on the bouba-kiki task. Twenty ASD participants and 20 matched controls were presented the bouba-kiki task. Autism-Quotient (AQ) scores and several cognitive measures were obtained for all participants. Results demonstrate that among all measures, only AQ scores were significantly correlated to the performance on the bouba-kiki task in the ASD group. Results thus support the existence of a relation between autism symptoms and performance on the bouba kiki task, and are discussed in light of current theories. PMID- 28987968 TI - The effect of asymmetrical limited hip flexion on seating posture, scoliosis and windswept hip distortion. AB - BACKGROUND: Postural asymmetries with seating problems are common in adults with cerebral palsy. AIMS: To analyse the prevalence of asymmetrical limited hip flexion (<90 degrees ) in adults with CP, and to evaluate the association between asymmetrical limited hip flexion and postural asymmetries in the sitting position. METHODS AND PROCEDURES: Cross-sectional data of 714 adults with CP, 16 73 years, GMFCS level I-V, reported to CPUP, the Swedish cerebral palsy national surveillance program and quality registry, from 2013 to 2015. Hip range of motion was analysed in relation to pelvic obliquity, trunk asymmetry, weight distribution, scoliosis and windswept hip distortion. OUTCOMES AND RESULTS: The prevalence of asymmetrical limited hip flexion increased as GMFCS level decreased. Of adults at GMFCS level V, 22% had asymmetrical limited hip flexion (<90 degrees ). The odds of having an oblique pelvis (OR 2.6, 95% CI:1.6-2.1), an asymmetrical trunk (OR 2.1, 95% CI:1.1-4.2), scoliosis (OR 3.7, 95% CI:1.3-9.7), and windswept hip distortion (OR 2.6, 95% CI:1.2-5.4) were higher for adults with asymmetrical limited hip flexion compared with those with bilateral hip flexion>90 degrees . CONCLUSIONS AND IMPLICATIONS: Asymmetrical limited hip flexion affects the seating posture and is associated with scoliosis and windswept hip distortion. PMID- 28987969 TI - Effectiveness of cognitive orientation to (daily) occupational performance (CO OP) on children with cerebral palsy: A mixed design. AB - BACKGROUND: Cerebral palsy (CP) is the most common cause of physical disabilities during childhood. Therapeutic interventions mainly focus on impairment reduction to address motor-based difficulties. In contrast, Cognitive Orientation to daily Occupational Performance (CO-OP) is a cognitive approach, providing intervention at the level of activity and participation. AIMS: This study aims to determine whether the CO-OP approach improves motor skills and achievement in motor-based occupational performance goals in children with CP. METHODS AND PROCEDURES: In this mixed design research (i.e., a multiple baseline single case experimental design and a one-group pretest-posttest design), five children with CP participated in 12 CO-OP intervention sessions. Repeated measures of motor skills for the multiple baseline single case experimental design were taken using the Bruininks-Oseretsky Test of Motor Proficiency (BOTMP); pre- and post-measures of parent/child perception of performance and satisfaction were identified using the Canadian Occupational Performance Measure (COPM); level of achievement was identified using Goal Attainment Scaling (GAS). OUTCOMES AND RESULTS: According to the BOTMP results, all children were able to engage in the CO-OP intervention to improve motor performance. Significant differences after treatment were found in both performance and performance satisfaction ratings using the COPM as rated by parents and children. The GAS results showed progress in achievement levels for all children; all goals were achieved or exceeded. CONCLUSIONS AND IMPLICATIONS: CO-OP intervention can be helpful in improving motor skills and achieving self-identified, motor-based goals in children with CP. PMID- 28987970 TI - An evaluation of the production effects of video self-modeling. AB - A multiple baseline across tasks design was used to evaluate the production effects of video self-modeling on three activities of daily living tasks of an adult male with Autism Spectrum Disorder and Intellectual Disability. Results indicated large increases in task accuracy after the production of a self modeling video for each task, but before the video was viewed by the participant. Results also indicated small increases when the participant was directed to view the same video self-models before being prompted to complete each task. PMID- 28987971 TI - Best seating condition in children with spastic cerebral palsy: One type does not fit all. AB - BACKGROUND: The effect of forward-tilting of the seat surface and foot-support in children with spastic cerebral palsy (CP) is debated. AIM: To assess the effect of forward-tilting of the seat surface and foot-support in children with CP on kinematic head stability and reaching. METHODS: Nineteen children functioning at Gross Motor Function Classification System levels I-III participated [range 6 12y; ten unilateral spastic CP (US-CP) and nine bilateral spastic CP (BS-CP)]. Kinematic data were recorded of head sway and reaching with the dominant arm in four sitting conditions: a horizontal and a 15 degrees forward (FW) tilted seat surface, each with and without foot-support. RESULTS: Seating condition did not affect head stability during reaching, but did affect kinematic reaching quality. The major reaching parameters, i.e., the proportion of reaches with one movement unit (MU) and the size of the transport MU, were not affected by foot-support. Forward-tilting had a positive effect on these parameters in children with US-CP, whereas the horizontal condition had this effect in children with BS-CP. IMPLICATIONS: A 15 degrees forward-tilted seating and foot-support do not affect head stability. Reaching in children with US-CP profits from forward-tilting; in children with BS-CP forward-tilting worsens reaching - effects that are independent of foot-support. PMID- 28987972 TI - Drop-out during a randomized trial with adolescents with intellectual disability was associated with participant burden, while drop-out at study exit was associated with carer and household characteristics. AB - BACKGROUND: People with intellectual disability are difficult to retain in longitudinal studies. Research on determinants of study retention for individual carer dyads, and their reasons for drop-out, are limited. AIMS: To investigate characteristics associated with drop-out, and to investigate whether characteristics varied by stage of drop-out. METHODS AND PROCEDURES: Data are from an Australian randomized trial with adolescents with intellectual disability living in the community. Characteristics of both the adolescent and their nominated carer were collected at baseline. Carers were sent an exit questionnaire approximately two years after enrolment. OUTCOMES AND RESULTS: Baseline information was available for 566 adolescents: 72(13.0%) withdrew during the study, and 96(17.3%) didn't return exit questionnaires. Characteristics associated with drop-out during the study were being in the intervention group, the carer being younger, and the carer not being one of the adolescent's parents. Characteristics associated with withdrawal at exit were carer having lower education and carer having lower socioeconomic status. No adolescent characteristic was associated with drop-out. CONCLUSIONS AND IMPLICATIONS: Characteristics of drop-outs weren't related to the adolescent and differed according to timing. Drop-out during the study was associated with study burden, whereas characteristics of drop-outs at exit interview were associated with lower social position. PMID- 28987973 TI - Effect of age at cochlear implantation and at exposure to Cued Speech on literacy skills in deaf children. AB - The aim of this study was to investigate how age at cochlear implantation (CI) and age at exposure to Cued Speech (CS, Manual system that resolves the ambiguity inherent lipreading) could impact literacy skills in deaf children. Ninety deaf children fitted with CI (early vs late) and exposed to CS (early vs late) from primary schools (from Grade 2 to Grade 5) took part in this study. Five literacy skills were assessed: phonological skills through phoneme deletion, reading (decoding and sentence comprehension), word spelling and vocabulary. The results showed that both age at CI and age at first exposure to CS had some influence on literacy skills but there was no interaction between these factors. This implies that the positive effects of age at CI, especially on all literacy skills in the younger children, were not strengthened by age at exposure to CS. PMID- 28987974 TI - Post-boosting of classification boundary for imbalanced data using geometric mean. AB - In this paper, a novel imbalance learning method for binary classes is proposed, named as Post-Boosting of classification boundary for Imbalanced data (PBI), which can significantly improve the performance of any trained neural networks (NN) classification boundary. The procedure of PBI simply consists of two steps: an (imbalanced) NN learning method is first applied to produce a classification boundary, which is then adjusted by PBI under the geometric mean (G-mean). For data imbalance, the geometric mean of the accuracies of both minority and majority classes is considered, that is statistically more suitable than the common metric accuracy. PBI also has the following advantages over traditional imbalance methods: (i) PBI can significantly improve the classification accuracy on minority class while improving or keeping that on majority class as well; (ii) PBI is suitable for large data even with high imbalance ratio (up to 0.001). For evaluation of (i), a new metric called Majority loss/Minority advance ratio (MMR) is proposed that evaluates the loss ratio of majority class to minority class. Experiments have been conducted for PBI and several imbalance learning methods over benchmark datasets of different sizes, different imbalance ratios, and different dimensionalities. By analyzing the experimental results, PBI is shown to outperform other imbalance learning methods on almost all datasets. PMID- 28987976 TI - A new approach to optimal control of conductance-based spiking neurons. AB - This paper presents an algorithm for solving the minimum-energy optimal control problem of conductance-based spiking neurons. The basic procedure is (1) to construct a conductance-based spiking neuron oscillator as an affine nonlinear system, (2) to formulate the optimal control problem of the affine nonlinear system as a boundary value problem based on Pontryagin's maximum principle, and (3) to solve the boundary value problem using the homotopy perturbation method. The construction of the minimum-energy optimal control in the framework of the homotopy perturbation technique is novel and valid for a broad class of nonlinear conductance-based neuron models. The applicability of our method in the FitzHugh Nagumo and Hindmarsh-Rose models is validated by simulations. PMID- 28987975 TI - Synchronization stability of memristor-based complex-valued neural networks with time delays. AB - This paper focuses on the dynamical property of a class of memristor-based complex-valued neural networks (MCVNNs) with time delays. By constructing the appropriate Lyapunov functional and utilizing the inequality technique, sufficient conditions are proposed to guarantee exponential synchronization of the coupled systems based on drive-response concept. The proposed results are very easy to verify, and they also extend some previous related works on memristor-based real-valued neural networks. Meanwhile, the obtained sufficient conditions of this paper may be conducive to qualitative analysis of some complex valued nonlinear delayed systems. A numerical example is given to demonstrate the effectiveness of our theoretical results. PMID- 28987978 TI - Global exponential stability of nonautonomous neural network models with unbounded delays. AB - For a nonautonomous class of n-dimensional differential system with infinite delays, we give sufficient conditions for its global exponential stability, without showing the existence of an equilibrium point, or a periodic solution, or an almost periodic solution. We apply our main result to several concrete neural network models, studied in the literature, and a comparison of results is given. Contrary to usual in the literature about neural networks, the assumption of bounded coefficients is not required to obtain the global exponential stability. Finally, we present numerical examples to illustrate the effectiveness of our results. PMID- 28987977 TI - Robust Alternating Low-Rank Representation by joint Lp- and L2,p-norm minimization. AB - We propose a robust Alternating Low-Rank Representation (ALRR) model formed by an alternating forward-backward representation process. For forward representation, ALRR first recovers the low-rank PCs and random corruptions by an adaptive local Robust PCA (RPCA). Then, ALRR performs a joint Lp-norm and L2,p-norm minimization (0

=8 where the high observed acute toxicity could not be explained, even by considering an equal contribution of CuOH+ and Cu2+ to the overall Cu toxicity. The 96-h LC50 values of 59% of 90 toxicity tests from 19 independent studies in the literature were reasonably well predicted by the new acute BLM. The LC20 predictions from the new chronic BLM were reasonable for 7 out of 14 toxicity tests from 6 independent chronic studies (with variable exposure durations). The observed deviations from BLM predictions may be due to uncertainties in the water chemistry in these literature studies and/or to differences in fish sensitivity. A residual pH effect was also observed for both the acute and the chronic data-sets, as the ratio of predicted vs. observed LC values generally increased with the pH. Additional mechanistic studies are required to understand the influence of pH, Na, and Mg on Cu toxicity to trout. The present study presents the first experimentally developed chronic Cu BLM for the rainbow trout. To the best of our knowledge, it also presents the first acute Cu BLM that is based on a published data-set for trout. These newly developed BLMs should contribute to improving the risk assessment of Cu to fish in freshwater. PMID- 28987992 TI - Effects of elevated CO2 levels on subcellular distribution of trace metals (Cd and Cu) in marine bivalves. AB - Hypercapnia (elevated CO2 levels) and pollution with trace metals such as Cu and Cd are common stressors in estuarine habitats that can negatively affect physiology and health of marine organisms. Hypercapnia can modulate toxicity of trace metals including Cu and Cd; however, the physiological and cellular mechanisms of the metal-CO2 interactions are not well understood. We investigated the effects of elevated PCO2 (~800 and 2000MUatm) and metal exposure (50MUgl-1 of Cu or Cd) on subcellular distribution of metals in two common species of marine bivalves, Eastern oysters Crassostrea virginica and hard shell clams Mercenaria mercenaria. Oysters accumulated higher burdens of Cu and Cd in the gill tissues compared to clams. In both studied species, Cu was predominantly associated with the metabolically active cell compartments (mitochondria, lysosomes, microsomes and cytosolic enzymes), with a modest fraction sequestered by metallothioneins (~30%) and the insoluble metal-containing granules (MCG) (~15-20%). Unlike Cu, Cd was largely sequestered by metallothioneins (~60-70%), with a relatively small fraction associated with the organelles and the cytosolic enzymes. Mitochondria were the main intracellular target for trace metals accumulating higher concentrations of Cd (and in the case of oysters - of Cu) than other organelles or cytosolic enzymes. Cu accumulation in the metabolically active cellular compartments was independent of the CO2 levels, while Cd content of the organelles and cytosolic enzymes increased at elevated PCO2 in both studied species indicating that hypercapnia may enhance cellular toxicity of Cd in bivalves. Hypercapnia suppressed the sequestration capacity of metallothioneins for Cu and Cd in oysters but increased Cu and Cd load in clam metallothioneins. Thus, metal-induced metabolic injury in oysters may be exaggerated by hypercapnia which enhances metal accumulation in the potentially sensitive intracellular fractions and suppresses the metal detoxification capacity. In contrast, clams appear to be more resistant to the combined effects of hypercapnia and metal exposure reflecting more efficient and robust detoxification mechanisms of this species. PMID- 28987993 TI - Corticomuscular coherence in the acute and subacute phase after stroke. AB - OBJECTIVE: Stroke is one of the leading causes of physical disability due to damage of the motor cortex or the corticospinal tract. In the present study we set out to investigate the role of adaptations in the corticospinal pathway for motor recovery during the subacute phase after stroke. METHODS: We examined 19 patients with clinically diagnosed stroke and 18 controls. The patients had unilateral mild to moderate weakness of the hand. Each patient attended two sessions at approximately 3days (acute) and 38days post stroke (subacute). Task related changes in the communication between motor cortex and muscles were evaluated from coupling in the frequency domain between EEG and EMG during movement of the paretic hand. RESULTS: Corticomuscular coherence (CMC) and intermuscular coherence (IMC) were reduced in patients as compared to controls. Paretic hand motor performance improved within 4-6weeks after stroke, but no change was observed in CMC or IMC. CONCLUSIONS: CMC and IMC were reduced in patients in the early phase after stroke. However, changes in coherence do not appear to be an efficient marker for early recovery of hand function following stroke. SIGNIFICANCE: This is the first study to demonstrate sustained reduced coherence in acute and subacute stroke. PMID- 28987994 TI - After-effects of transcranial alternating current stimulation on evoked delta and theta power. AB - OBJECTIVE: Phase synchronization is suggested to be among the mechanisms that can explain the effects of transcranial alternating current stimulation (tACS). However, little is known about the effects of tACS on event-related oscillatory activity. Therefore the objective was to investigate frequency-related effects of frontal tACS on event-related oscillatory power. METHODS: In a double blind randomized controlled cross-over design, twenty-four participants received 12min of delta (2.5Hz), theta tACS (5Hz) and sham tACS at an intensity of 1mA peak-to peak. Event-related delta- and theta-related oscillatory activity was recorded to reward- and punishment-related feedback signals. RESULTS: Delta tACS decreased feedback-related oscillatory power in the 1.5 and 3.5Hz frequency range. This effect was driven by power changes below the tACS frequency stimulation. CONCLUSION: Exogenous field potentials can attenuate event-related oscillatory activity in a rhythm slightly below the stimulation frequency. Our findings suggest an interaction between tACS and event-related rhythmic activity that extends beyond phase synchronization. SIGNIFICANCE: These findings add novel insights into the mechanisms of tACS after-effects. PMID- 28987995 TI - Separation, identification and quantification of carotenoids and chlorophylls in dietary supplements containing Chlorella vulgaris and Spirulina platensis using High Performance Thin Layer Chromatography. AB - In this study, 14 commercial products (dietary supplements) containing alga Chlorella vulgaris and cyanobacteria Spirulina platensis, originated from China and Japan, were analysed. UV-vis spectrophotometric method was applied for rapid determination of chlorophylls, carotenoids and pheophytins; as degradation products of chlorophylls. High Performance Thin-Layer Chromatography (HPTLC) was used for effective separation of these compounds, and also Atomic Absorption Spectrometry for determination of heavy metals as indicator of environmental pollution. Based on the results obtained from UV-vis spectrophotometric determination of photosynthetic pigments (chlorophylls and carotenoids), it was confirmed that Chlorella vulgaris contains more of all these pigments compared to the cyanobacteria Spirulina platensis. The fastest mobility compound identified in Chlorella vulgaris and Spirulina platensis using HPTLC method was beta carotene. Spectral analysis and standard calibration curve method were used for identification and quantification of separated substances on Thin-Layer Chromatographic plate. Quantification of copper (Cu2+, at 324.7 nm) and zinc (Zn2+, at 213.9nm) was performed using Flame Atomic Absorption Spectrometry with air-acetylene flame atomization. Quantification of cadmium (Cd2+, at 228.8 nm), nickel (Ni2+, at 232.0nm) and lead (Pb2+, at 283.3nm) by Electrothermal Graphite Furnace Atomic Absorption Spectrometry; and quantification of mercury (Hg2+, at 254nm) by Cold Vapour Atomic Absorption Spectrometry. PMID- 28987996 TI - Pharmacokinetic comparison of seven major bioactive components in normal and depression model rats after oral administration of Baihe Zhimu decoction by liquid chromatography-tandem mass spectrometry. AB - A simple and rapid liquid chromatography-tandem mass spectrometry method was firstly developed for simultaneous quantification of neomangiferin, mangiferin, regaloside A, regaloside I, timosaponin BII, anemarsaponin E and timosaponin AIII in rat plasma after oral administration of Baihe Zhimu decoction, which plays an important role for the treatment of depression. The plasma samples were pretreated by a one-step direct protein precipitation with methanol. Separation of the seven components and scutellarin (IS) from endogenous components with high selectivity and sensitivity (LLOQ, 0.1-1.0ng/mL) was achieved within 10min using Poroshell 120 EC-C18 column (150mm*3.0mm, 2.7MUm). A gradient mobile phase consisting of acetonitrile and water (containing 5mM ammonium acetate) was applied at a flow rate of 0.4mL/min. Detection and measurement were performed on an AB Sciex QTRAP(r) 5500 mass spectrometer in multiple reactions monitoring mode. The intra- and inter-day precisions were all within 15% and the accuracies were in the range of -10.4% to 14.5%. The recovery ranged from 90.8 to 113.8%. The validated method was successfully applied to pharmacokinetic study of the seven components in normal and chronic unpredicted mild stress-induced depression model rats. PMID- 28987997 TI - Immediate hypersensitivity to penicillins. Identification of a new antigenic determinant. AB - The study of adverse drug reactions (ADRs) constitutes a challenge in the area of Medicine. Drugs generate a large number of the total registered hypersensitivity reactions, where penicillins are responsible for more than half of them. In vitro tests in the market are not efficient enough since they lack in sensitivity and specificity. This is the reason why in vivo tests are carried out, with the subsequent danger to the patient's life. It is essential to discover new beta lactam antigenic determinants to develop more effective detection systems and thus, obtain better explanations of the allergic mechanisms related to these drugs. We propose a strategy based on the use of "peptide probes", small labeled and chemical active peptides which have been structurally modified for reacting with the beta-lactam moiety at different conditions. The probes also contain a biotin group for application in an immunoassay format. Three different amoxicillin adducts have been obtained, purified and characterized by HPLC-MS and NMR techniques. These results have helped us to elucidate and propose a new antigenic determinant for beta-lactams, named the "penamidyl" epitope. All the adducts have been validated and evaluated with sera from different penicillin allergic patients by means of a Magneto-ELISA, immunochemical technique that has allowed us to detect specific IgEs in a very high percentage of the serum samples. An immunoassay has been developed, validated and applied as a diagnostic tool for the detection of specific IgEs in the sera of penicillin allergic patients using a new antigenic determinant. PMID- 28987998 TI - Monitoring and Targeting Anti-VEGF Induced Hypoxia within the Viable Tumor by 19F MRI and Multispectral Analysis. AB - The effect of anti-angiogenic agents on tumor oxygenation has been in question for a number of years, where both increases and decreases in tumor pO2 have been observed. This dichotomy in results may be explained by the role of vessel normalization in the response of tumors to anti-angiogenic therapy, where anti angiogenic therapies may initially improve both the structure and the function of tumor vessels, but more sustained or potent anti-angiogenic treatments will produce an anti-vascular response, producing a more hypoxic environment. The first goal of this study was to employ multispectral (MS) 19F-MRI to noninvasively quantify viable tumor pO2 and evaluate the ability of a high dose of an antibody to vascular endothelial growth factor (VEGF) to produce a strong and prolonged anti-vascular response that results in significant tumor hypoxia. The second goal of this study was to target the anti-VEGF induced hypoxic tumor micro-environment with an agent, tirapazamine (TPZ), which has been designed to target hypoxic regions of tumors. These goals have been successfully met, where an antibody that blocks both murine and human VEGF-A (B20.4.1.1) was found by MS 19F-MRI to produce a strong anti-vascular response and reduce viable tumor pO2 in an HM-7 xenograft model. TPZ was then employed to target the anti-VEGF-induced hypoxic region. The combination of anti-VEGF and TPZ strongly suppressed HM-7 tumor growth and was superior to control and both monotherapies. This study provides evidence that clinical trials combining anti-vascular agents with hypoxia-activated prodrugs should be considered to improved efficacy in cancer patients. PMID- 28987999 TI - Novel technology as platform for interventions for caregivers and individuals with severe mental health illnesses: A systematic review. AB - BACKGROUND: Severe mental illnesses (SMIs) have been found to be associated with both increases in morbidity-mortality, need for treatment care in patients themselves, and burden for relatives as caregivers. A growing number of web-based and mobile software applications have appeared that aim to address various barriers with respect to access to care. Our objective was to review and summarize recent advancements in such interventions for caregivers of individuals with a SMI. METHODS: We conducted a systematic search for papers evaluating interactive mobile or web-based software (using no or only minimal support from a professional) specifically aimed at supporting informal caregivers. We also searched for those supporting patients with SMI so as to not to miss any which might include relatives. RESULTS: Out of a total of 1673 initial hits, we identified 11 articles reporting on 9 different mobile or web-based software programs. The main result is that none of those studies focused on caregivers, and the ones we identified using mobile or web-based applications were just for patients and not their relatives. LIMITATIONS: Differentiating between online and offline available software might not always have been totally reliable, and we might have therefore missed some studies. CONCLUSIONS: In summary, the studies provided evidence that remotely accessible interventions for patients with SMI are feasible and acceptable to patients. No such empirically evaluated program was available for informal caregivers such as relatives. Keeping in mind the influential role of those informal caregivers in the process of treatment and self-management, this is highly relevant for public health. Supporting informal caregivers can improve well-being of both caregivers and patients. PMID- 28988000 TI - Development and assessment of stressful life events subscales - A preliminary analysis. AB - BACKGROUND: Stress affects people of all ages, genders, and cultures and is associated with physical and psychological complications. Stressful life events are an important research focus and a psychometrically valid measure could provide useful clinical information. The purpose of the study was to develop a reliable and valid measurement of stressful life events and to assess its reliability and validity using established measures of social support, stress, depression, anxiety and maternal and child health. METHODS: The authors used an adaptation from the Social Readjustment Rating Scale (SRRS) to describe the prevalence of life events; they developed a 4-factor stressful life events subscales and used Medical Outcomes Social Support Scale, Social Support Scale, Depression, Anxiety and Stress Scale and 14 general health items for validity analysis. Analyses were performed with descriptive statistics, Cronbach's alpha, Spearman's rho, Chi-square test or Fisher's exact test and Wilcoxon 2-sample test. RESULTS: The 4-factor stressful life events subscales showed acceptable reliability. The resulting subscale scores were significantly associated with established measures of social support, depression, anxiety, stress, and caregiver health indicators. LIMITATIONS: The study presented a number of limitations in terms of design and recall bias. CONCLUSIONS: Despite the presence of a number of limitations, the study provided valuable insight and suggested that further investigation is needed in order to determine the effectiveness of the measures in revealing the family's wellbeing and to develop and strengthen a more detailed analysis of the stressful life events/health association. PMID- 28988001 TI - Prevalence of and risk factors for non-suicidal self-injury in rural China: Results from a nationwide survey in China. AB - BACKGROUND: Non-suicidal self-injury (NSSI) is a highly prevalent and serious public health problem among adolescents worldwide. However, to date there were no studies assessing the prevalence of NSSI defined by suggested DSM-5 criteria among Chinese adolescents. We aimed to conduct a nationwide survey to explore the prevalence of and risk factors for NSSI among school-based adolescents in rural China. METHODS: A total sample of 15,623 adolescents in rural China were enrolled by using a multistage sampling method. Data was collected by self-report questionnaires including demographic characteristics, neglect, maltreatment, loneliness, resilience, social support and emotional management ability. NSSI was defined by suggested DSM-5 criteria, according to which the engagement in self injury took place more than 5 times a year. Multinomial logistic regression models were used to estimate the association between risk factors and NSSI. RESULTS: There were 12.2% of adolescents (n = 1908) met the suggested DSM-5 criteria. Approximately 29% reported a history of NSSI at least once during the last year. Significant differences were found in several demographic factors including gender, ethnicity, grade, and family structure between adolescents with and without experiencing NSSI. The top three NSSI behaviors among adolescents with NSSI experience were hitting self, pinching, and pulling hair, with a prevalence rate of 16.7%, 14.1% and 11.2%, respectively. Female, Han ethnicity, fathers' education level, neglect, maltreatment, loneliness, social support, suicidal behaviors and emotional management ability were significantly associated with NSSI by multivariate analysis. No significant relationship was found between resilience and risk of NSSI. LIMITATION: The DSM-5 has proposed 6 groups of criteria for NSSI, we only used criteria on frequency given its more accepted feasibility and pragmatic application. Consequently, it may different from other prevalence that estimated by other criteria. CONCLUSION: To the best of our knowledge, this is the first study reporting prevalence of NSSI defined by suggested DSM-5 criteria among adolescent in rural China. In comparison to finding from the similar samples of adolescents, Chinese rural adolescents seem to have a relative higher prevalence. The potential risk factors for NSSI include female, father's education, Han ethnicity, psychosocial factors and suicide behaviors. More evidence for further understanding of context of the occurrence, improving access to health care utilization, and identifying the role of psychosocial factors and family relationship, is needed for the prevention and management of NSSI. PMID- 28988002 TI - The effect of sepsis and septic shock on the viscoelastic properties of clot quality and mass using rotational thromboelastometry: A prospective observational study. AB - PURPOSE: The study purpose was to define changes in coagulation across the sepsis spectrum using rotational thromboelastometry (ROTEM). METHODS: Sepsis patients were recruited on admission to the Emergency Department and Intensive Care Units of a large teaching hospital in Wales. ROTEM markers of clot development and fibrinolysis were determined, as well as standard coagulation markers. A healthy control group matched for age and gender was also recruited (n=44). RESULTS: 100 patients were recruited (50 sepsis, 20 severe sepsis and 30 septic shock). Maximum clot firmness was significantly higher in the sepsis (p<0.001) and severe sepsis (p=0.012) groups than the healthy control (71.6+/-4.5 and 70.4+/-4.1 vs 64.4 respectively). In septic shock there was prolonged clot development; however, maximum clot firmness remained normal. Fibrinolytic function was significantly impaired in septic shock, which was also significantly associated with 28-day mortality (p<0.001). CONCLUSIONS: ROTEM indicated significantly enhanced clot structural development in sepsis and severe sepsis, which could be indicative of a hypercoagulable phase. In septic shock, despite there being a prolongation of clotting pathways and impaired fibrinolysis, clot mass was comparably normal, suggestive of the development of a clot with healthy characteristics. PMID- 28988003 TI - Folate deficiency in patients seeking treatment of alcohol use disorder. AB - INTRODUCTION: Nutritional deficiency is frequent in patients with an alcohol use disorder (AUD). We aimed to analyze serum and erythrocyte folate deficiency in a case series of patients that initiated treatment of AUD. PATIENTS AND METHODS: A cross-sectional study in patients admitted for detoxification between 2007 and 2015 was performed. Sociodemographic characteristics, history of alcohol consumption, type of alcohol, and medical co-morbidity were assessed at admission. Blood samples for biochemistry and hematological parameters were collected at admission. Logistic regression models were used to establish predictors of folate deficiency. RESULTS: 211 patients (79.1% men) were eligible; age at admission was 46 years [IQR:40-51], and the amount of alcohol consumption was of 160g/day [IQR:120-200]. Thirty four percent of patients had macrocytosis (MCV>100fL), 12.8% had anemia, 23% of cases presented with serum folate deficiency and 7% presented with erythrocyte folate deficiency. Most (69%) of the patients with serum folate deficiency had normal erythrocyte folate levels. In univariate analysis, macrocytosis (OR=3.4, 95%CI:1.7-6.6), alcohol-related liver disease (ARLD) (OR=2.5, 95%CI:1.0-6.1) and drinking alcoholic beverages other than beer (OR=3.3, 95%CI:1.5-7.3) were associated with folate deficiency. However, only macrocytosis was significantly associated with serum folate deficiency in multivariate analysis (OR=3.1, 95%CI:1.1-8.9). Macrocytosis (P<0.001), ARLD (P=0.01) and the type of alcohol consumption (P<0.001) were factors associated with erythrocyte folate deficiency in univariate analysis. In multivariate analysis only macrocytosis remained significantly associated to erythrocyte folate deficiency (P=0.037). CONCLUSION: Folate deficiency is a relatively frequent finding in contemporary, middle-aged patients with AUD, and macrocytosis is significantly associated with the deficiency. PMID- 28988004 TI - The role of restraint omission in alcohol-related traffic fatalities. AB - BACKGROUND AND AIMS: Fatal traffic accidents affect thousands of people in the US alone every year. Alcohol consumption has been identified as a strong predictor of traffic fatalities. This result is hardly surprising as drivers who decide to consume alcohol and then drive are more likely to exhibit poor driving performance. In this paper, I argue that alcohol consumption can lead to traffic fatalities by increasing restraint omission. METHODS: I analyzed individual-level data about victims (n=488,829) of fatal traffic accidents that occurred in the US between January 1, 1999 and December 31, 2015 from the Fatality Analysis Reporting System of the National Highway Traffic and Safety Administration. RESULTS: There is a strong relationship between alcohol consumption and restraint use. Both vehicle drivers and occupants are far less likely to be restrained when inebriated. Additional analyses show that part of the effect of alcohol consumption on traffic fatalities can be attributed to restraint omission. CONCLUSIONS: There is a significant relationship between alcohol consumption and restraint omission for both drivers and occupants of vehicles that were involved in fatal traffic accidents in the US between January 1999 and December 2015. Past public health campaigns have focused on preventing traffic fatalities by persuading drivers to refrain from getting behind the wheel after consuming alcohol. My data suggest that public health campaigns should inform both drivers and occupants of vehicles about the relationship between alcohol and restraint omission in order to minimize future casualties. PMID- 28988005 TI - A longitudinal study of electronic cigarette use and onset of conventional cigarette smoking and marijuana use among Mexican adolescents. AB - PURPOSE: This study evaluated whether e-cigarette trial among Mexican adolescents increased the likelihood of trial and use of conventional cigarettes or marijuana use at follow-up. METHOD: A school-based longitudinal survey was conducted in 60 public middle schools from the three largest cities in Mexico. Students (12 13years old) were surveyed in 2015 and followed up 20 months later (n=6574). Generalized estimating equations models were used to evaluate the association between e-cigarette trial at baseline and conventional cigarettes smoking and marijuana use at follow-up. RESULT: Adolescents who had tried e-cigarettes (but not cigarettes) at baseline were more likely to have tried conventional cigarettes at followup compared to adolescents who had tried neither e-cigarettes nor cigarettes (43% vs. 24%, respectively; RR 1.41, 95% CI 1.18-1.70). We also found that adolescents who had tried both conventional cigarettes and e cigarettes at baseline were more likely to have tried marijuana at follow-up compared to adolescents who had tried neither tobacco product (20% vs. 4%, respectively; RR 2.67, 95% CI 1.78-4.02). Trial of only e-cigarettes was not independently associated with marijuana use at followup. CONCLUSIONS: Adolescents who had tried e-cigarettes were more likely to have tried conventional cigarettes and marijuana 20 months later. Although e-cigarettes have been banned in Mexico, it is likely that additional policies and public health campaigns are needed to reduce adolescent use of e-cigarettes and its consequences. PMID- 28988006 TI - Building abstinent networks is an important resource in improving quality of life. AB - AIMS: To investigate changes in social network and quality of life of a substance use disorder cohort as they progressed through treatment. DESIGN: Multi-site, prospective, observational study of 338 adults entering substance use disorder treatment. SETTING: Patients at 21 facilities across Norway contributed baseline data when they initiated treatment, and follow-up data was collected from them one year later. METHODS: The cohort was divided into those who completed, dropped out, and remained in treatment one year after treatment initiation. For each treatment status group, general linear models with repeated measures analyzed global and social quality of life with the generic QOL10 instrument over time. The between-group factor was a change in social network variable from the EuropASI. FINDINGS: Those who gained an abstinent network reported the largest quality of life improvements. Improvements were smallest or negligible for the socially isolated and those who were no longer in contact with the treatment system. CONCLUSIONS: Developing an abstinent network is particularly important to improve the quality of life of those in substance use disorder treatment. Social isolation is a risk factor for impaired quality of life throughout the treatment course. PMID- 28988007 TI - Chromosome copy number variation in telomerized human bone marrow stromal cells; insights for monitoring safe ex-vivo expansion of adult stem cells. AB - Adult human bone marrow stromal cells (hBMSC) cultured for cell therapy require evaluation of potency and stability for safe use. Chromosomal aberrations upsetting genomic integrity in such cells have been contrastingly described as "Limited" or "Significant". Previously reported stepwise acquisition of a spontaneous neoplastic phenotype during three-year continuous culture of telomerized cells (hBMSC-TERT20) didn't alter a diploid karyotype measured by spectral karyotype analysis (SKY). Such screening may not adequately monitor abnormal and potentially tumorigenic hBMSC in clinical scenarios. We here used array comparative genomic hybridization (aCGH) to more stringently compare non tumorigenic parental hBMSC-TERT strains with their tumorigenic subcloned populations. Confirmation of a known chromosome 9p21 microdeletion at locus CDKN2A/B, showed it also impinged upon the adjacent MTAP gene. Compared to reference diploid human fibroblast genomic DNA, the non-tumorigenic hBMSC-TERT4 cells had a copy number variation (CNV) in at least 14 independent loci. The pre tumorigenic hBMSC-TERT20 cell strain had further CNV including 1q44 gain enhancing SMYD3 expression and 11q13.1 loss downregulating MUS81 expression. Bioinformatic analysis of gene products reflecting 11p15.5 CNV gain in tumorigenic hBMSC-TERT20 cells highlighted networks implicated in tumorigenic progression involving cell cycle control and mis-match repair. We provide novel biomarkers for prospective risk assessment of expanded stem cell cultures. PMID- 28988008 TI - Superior catalytic activity of Pt/carbon nanohorns nanocomposites toward methanol and formic acid oxidation reactions. AB - Pt nanoparticle-loaded carbon nanohorns (Pt/CNHs) nanocomposites were synthesized by using formic acid as reducing agent at room temperature. Taking the advantage of the high surface area and excellent electronic conductivity, CNHs were used as support without any pretreatments for the enhancement of catalytic performance. By adjusting the feeding amount of H2PtCl6, the mass, size and distribution of Pt nanoparticles could be effectively controlled on CNHs. Compared with commercial Pt/C, the synthesized Pt/CNHs exhibit higher catalytic activity and improved long term stability toward both methanol and formic acid oxidations. Among the Pt/CNHs, 13% wt. Pt/CNHs exhibit the best catalytic performances for the small size (2.4 nm) and uniform distribution of Pt NPs on CNHs. Our work reveals the superior catalytic performance of Pt/CNHs which may be a promising substitute for commercial Pt/C. PMID- 28988009 TI - Formation, physicochemical and interfacial study of carbamate surfactants. AB - Carbon dioxide is commonly used as pH regulator in switchable surfactant systems and in the formation of alkyl ammonium-alkyl carbamate ion-pair. Its use to form a meta-stable anionic surfactant has been less explored and can impart a cleavable character to the amphiphile. The reaction between CO2 and an alkylamine, N,N-di(propylamino)dodecylamine (Y12-amine), under alkaline pH conditions, produced a stable anionic carbamate-based surfactant (Y12-carbamate). By heating and exposure to N2, anionic Y12-carbamate could slowly be reverted into Y12-amine. The surface activity of Y12-amine and Y12-carbamate was investigated by surface tension measurements. To study the behavior of Y12-amine at the gas-water interface during CO2 exposure, we used the pendant drop technique with a sealed chamber where the gas composition could be controlled. The Y12-carbamate had a higher CMC than Y12-amine at pH 12, and was also less surface active. The ion pair Y12-ammonium - Y12-carbamate, obtained at neutral pH, exhibited the lowest CMC and the highest surface activity. The interfacial formation of anionic Y12-carbamate induced an increase in surface tension. When CO2 was exchanged to N2, the migration from the bulk to the interface of Y12 amine induced a decrease in surface tension. The rate was dependent on the concentration of Y12-amine. PMID- 28988010 TI - A new microporous oxyfluorinated titanium(IV) phosphate as an efficient heterogeneous catalyst for the selective oxidation of cyclohexanone. AB - Designing a new porous nanomaterial for eco-friendly catalytic reactions is very challenging. Here, a new crystalline microporous oxyfluorinated titanium phosphate material (TIPO-1) has been synthesized under hydrothermal conditions in the absence of any structure directing agent. The triclinic crystalline phase with the unit cell parameters a=7.962A, b=10.006A, c=13.979A, alpha=96.921 degrees , beta=95.851 degrees and gamma=93.760 degrees has been indexed for TIPO-1 and it has been characterized through powder X-ray diffraction, nitrogen adsorption/desorption, XPS, FT-IR, 31P MAS NMR spectroscopy, UHR-TEM, FE-SEM and TGA/DTA analysis. The material exhibited excellent catalytic activity in liquid phase partial oxidation of cyclohexanone to adipic acid (up to 92% conversion) in the presence of aqueous H2O2 as oxidant together with value added side products like 1,6-hexandial and epsilon-caprolactone for reactions in different solvents. The material showed excellent recycling efficiency for six consecutive reaction cycles without any significant loss in catalytic activity. PMID- 28988011 TI - Coordinated morphogenesis of neurons and glia. AB - Glia adopt remarkable shapes that are tightly coordinated with the morphologies of their neuronal partners. To achieve these precise shapes, glia and neurons exhibit coordinated morphological changes on the time scale of minutes and on size scales ranging from nanometers to hundreds of microns. Here, we review recent studies that reveal the highly dynamic, localized morphological changes of mammalian neuron-glia contacts. We then explore the power of Drosophila and C. elegans models to study coordinated changes at defined neuron-glia contacts, highlighting the use of innovative genetic and imaging tools to uncover the molecular mechanisms responsible for coordinated morphogenesis of neurons and glia. PMID- 28988012 TI - Healing activity of proteolytic fraction (P1G10) from Vasconcellea cundinamarcensis in a cutaneous wound excision model. AB - The proteolytic enzymes from Vasconcellea cundinamarcensis have demonstrated efficacy to accelerate healing of skin lesions. We report here the efficacy of the proteolytic fraction - P1G10 during repair of excisional wounds in rodent model and analyze possible mediators involved. Using 0.05% P1G10 we observed on day 3rd increased wound contraction accompanied by an increase in activated neutrophils and VEGF relative to the control. On day 7th neutrophils returned to normal levels, and at 0.01% P1G10, an increase in NAG activity used to monitor monocyte/macrophage, was observed. On the other hand, on day 7th, we observed a decrease in TGF-beta at 0.05% P1G10, accompanied by an increased transformation of the latent TGF-beta to its active form. Also, on day 7th a reduction in MMP-9 activity and the number of apoptotic cells was observed along with an increase in fibroblast levels. Morphometrically, it appears that treatment with P1G10 accelerates the decline of initial inflammatory phase and reduces some unwanted effects likely caused by remaining TGF-beta or MMPs, thus enhancing the quality of scar. Overall, these data suggest that the active proteolytic fraction P1G10 enhances the efficacy of repair in excisional cutaneous wounds. PMID- 28988013 TI - Aloe vera gel improves behavioral deficits and oxidative status in streptozotocin induced diabetic rats. AB - Oxidative stress has a major role in progression of diabetes-related behavioral deficits. It has been suggested that Aloe vera has anti-diabetic, antioxidative, and neuroprotective effects. The present study was designed to determine the effects of Aloe vera gel on behavioral functions, oxidative status, and neuronal viability in the hippocampus of streptozotocin (STZ)-induced diabetic rats. Fifty five adult male Wistar rats were randomly divided into five groups, including: control (normal saline 8ml/kg/day; P.O.), diabetic (normal saline 8ml/kg/day; P.O.), Aloe vera gel (100mg/kg/day; P.O.), diabetic+Aloe vera gel (100mg/kg/day; P.O.) and diabetic+NPH insulin (10 IU/kg/day; S.C.). All treatments were started immediately following confirmation of diabetes in diabetic groups and were continued for eight weeks. Behavioral functions were evaluated by employing standard behavioral paradigms. Additionally, oxidative status and neuronal viability were assessed in the hippocampus. The results of behavioral tests showed that diabetes enhanced anxiety/depression-like behaviors, reduced exploratory and locomotor activities, decreased memory performance, and increased stress related behaviors. These changes in diabetic rats were accompanied by increasing oxidative stress and neuronal loss in the hippocampus. Interestingly, eight weeks of treatment with Aloe vera gel not only alleviated all the mentioned deficits related to diabetes, but in some aspects, it was even more effective than insulin. In conclusion, the results suggest that both interrelated hypoglycemic and antioxidative properties of Aloe vera gel are possible mechanisms that improve behavioral deficits and protect hippocampal neurons in diabetic animals. PMID- 28988015 TI - The dose-dependent effect of SOX9 and its incidence in colorectal cancer. AB - A member of the Sry-related HMG-box family of transcription factors (SOX9) is a transcription factor that belongs to the superfamily of High Mobility Group (HMG) domain transcription factors. SOX9 is expressed in a variety of tissues, including as the intestinal epithelium, where it is now recognised as an important actor for homeostasis. Beside, a high level of SOX9 has recently been correlated with a good prognosis for stage II colorectal cancers. However, growing evidence indicates that deciphering the function of SOX9 in the intestine has to take into account a dose-dependent effect of SOX9. Given the recurrent controversies and the lack of a state of the art as to whether SOX9 behaves like a tumour suppressor or an oncogen in the intestine epithelium, it is time to provide an update of the accumulated knowledge about the biological function of SOX9 in the intestine and about the role of SOX9 in colorectal cancers. PMID- 28988014 TI - L-Asparaginase of Leishmania donovani: Metabolic target and its role in Amphotericin B resistance. AB - Emergence of Amphotericin B (AmB) resistant Leishmania donovani has posed major therapeutic challenge against the parasite. Consequently, combination therapy aimed at multiple molecular targets, based on proteome wise network analysis has been recommended. In this regard we had earlier identified and proposed L asparaginase of Leishmania donovani (LdAI) as a crucial metabolic target. Here we report that both LdAI overexpressing axenic amastigote and promastigote forms of L. donovani survives better when challenged with AmB as compared to wild type strain. Conversely, qRT-PCR analysis showed an upregulation of LdAI in both forms upon AmB treatment. Our data demonstrates the importance of LdAI in imparting immediate protective response to the parasite upon AmB treatment. In the absence of structural and functional information, we modeled LdAI and validated its solution structure through small angle X-ray scattering (SAXS) analysis. We identified its specific inhibitors through ligand and structure-based approach and characterized their effects on enzymatic properties (Km, Vmax, Kcat) of LdAI. We show that in presence of two of the inhibitors L1 and L2, the survival of L. donovani is compromised whereas overexpression of LdAI in these cells restores viability. Taken together, our results conclusively prove that LdAI is a crucial metabolic enzyme conferring early counter measure against AmB treatment by Leishmania. PMID- 28988016 TI - Characterisation of the immune-related transcriptome in resected biliary tract cancers. AB - : Although biliary tract cancers (BTCs) are known to have an inflammatory component, a detailed characterisation of immune-related transcripts has never been performed. In these studies, nCounter PanCancer Immune Profiling Panel was used to assess the expression of 770 immune-related transcripts in the tumour tissues (TTs) and matched adjacent tissues (ATs) of resected BTCs. Cox regression analysis and Kaplan-Meier methods were used to correlate findings with relapse free survival (RFS). The first analysis in the TT and AT of an exploratory set (n = 22) showed deregulation of 39 transcripts associated with T-cell activation. Risk of recurrence was associated with a greater number of genes deregulated in AT in comparison to TT. Analysis in the whole set (n = 53) showed a correlation between AT cytotoxic T-lymphocyte antigen-4 (CTLA4) expression and RFS, which maintained statistical significance at multivariate analysis. CTLA4 expression correlated with forkhead box P3 (FOXP3) expression, suggesting enrichment in T regulatory cells. CTLA4 is known to act by binding to the cluster of differentiation 80 (CD80). No association was seen between AT CD80 expression and RFS. However, CD80 expression differentiated prognosis in patients who received adjuvant chemotherapy. We showed that the immunomodulatory transcriptome is deregulated in resected BTCs. Our study includes a small number of patients and does not enable to draw definitive conclusions; however, it provides useful insights into potential transcripts that may deserve further investigation in larger cohorts of patients. TRANSCRIPT PROFILING: Nanostring data have been submitted to GEO repository: GSE90698 and GSE90699. PMID- 28988018 TI - Corpus callosum diffusion abnormalities in refractory epilepsy associated with hippocampal sclerosis. AB - OBJECTIVES: To detect by diffusion tensor imaging (DTI) the extent of microstructural integrity changes of the corpus callosum (CC) in patients with hippocampal sclerosis (HS) and to evaluate possible association with clinical characteristics. METHODS: Fourty-two patients with temporal lobe epilepsy (TLE) and HS and 30 control subjects were studied with DTI. We grouped patients according to lesion side (left or right) HS. Mean diffusivity (MD), fractional anisotropy (FA), radial (RD) and axial diffusivity (AD) were extracted from five segments in CC midsagittal section obtained by automatic segmentation. CC DTI findings were compared between groups. We also evaluated association of DTI changes and clinical characteristics. RESULTS: HS patients displayed decreased FA and increased MD and RD in the anterior, mid-posterior and posterior CC segments, compared to controls. No differences were observed in AD. Patients reporting febrile seizure as the initial precipitating event presented more intense diffusion changes. No differences were seen comparing left and right HS. Age at epilepsy onset, disease duration and seizure frequency were not associated with DTI findings. CONCLUSIONS: This is one of the largest series of TLE-HS patients evaluating CC white matter fiber integrity by DTI, which allowed us to study how some clinical characteristics, such as seizure frequency, disease duration and lesion side, are related to CC integrity. Occurrence of febrile seizure was the only factor that had significant impact on tract integrity. Diffusion changes were not restricted to the posterior part of the CC; we observed the same changes for the anterior part of the CC. Diffusion changes were characterized by an increase in RD, while the AD remained intact for all regions of the CC. PMID- 28988017 TI - Evaluating the scientific basis of quality indicators in colorectal cancer care: A systematic review. AB - AIM: In colorectal cancer care, many indicators for assessment and improvement of quality of care are being used. These quality indicators serve as national and international benchmarks to compare health care on hospital and patient level. However, the scientific basis of these indicators is often unclear. Therefore, the aim of this systematic review is to examine reported quality indicators used in multidisciplinary colorectal cancer care and categorise these indicators based on scientific evidence. METHODS: We searched PubMed from 2005 to 2015 for original articles reporting on development, evaluation or validation of quality indicators in colorectal cancer care. Included articles were categorised in consensus-based, evidence-based and validation cohort studies. Extracted quality indicators were divided into structure, process and outcome indicators and grouped per discipline(s) involved. RESULTS: From 1163 studies, 41 articles were included: 12 (29%) consensus-based, 7 (17%) evidence-based and 22 (54%) validation cohort studies. In total, we identified 389 reported quality indicators: consensus-based (n = 349), evidence-based (n = 7) and validation (n = 33), respectively. Of all reported indicators, 45% (n = 186) concerned surgical items. The vast majority were process indicators (n = 315; 81%) and the remaining outcome (n = 57; 15%) or structure measurements (n = 17; 4%). Only 5 indicators were reported in the majority (>=7/12 articles) of consensus-based papers and 7 indicators were successfully validated. CONCLUSIONS: There is an abundance of reported colorectal cancer quality indicators, of which the majority are surgical, consensus-based process measures, which have not been validated in cohort studies. There is a need for international consensus on a limited evidence based data set of validated quality indicators, with a focus on outcome indicators. PMID- 28988019 TI - Acute intermittent porphyria after right hemi-colectomy. AB - INTRODUCTION: Acute intermittent porphyria is a rare autosomal dominant metabolic disease. It is caused by a genetic mutation that results in deficiency of porphobilinogen deaminase enzyme, the third enzyme in heme biosynthesis. Acute intermittent porphyria precipitated by surgery is very rare. CASE PRESENTATION: We present a 24 year-old woman who developed acute intermittent porphyria five days after right hemi-colectomy. Her presentation included neuro-visceral and psychiatric manifestations, and severe hyponatremia. She received critical care symptomatic management including mechanical ventilation. The diagnosis was based on a positive urine test for porphobilinogen and confirmed by the presence of a heterozygous mutation in the hydroxyrmethylbilane synthase (HMBS) gene (c.760delC p Leu254). DISCUSSION: Acute intermittent porphyria is the most common and life threatining type of acute porphyrias. It is more common in women and usually presents after puberty with acute abdominal pain and diverse neuro-psychiatric manifestations that can be confused with several surgical and medical diseases. Acute intermittent porphyria after surgery is most likely due to postoperative pain and low-calorie intake. Once suspected, prompt ICU management including high calorie intake are necessary to avoid serious complications and mortality before starting definitive treatment with hematin. CONCLUSION: Acute intermittent porphyria should be suspected in any patient, particularly young women, who develop diverse neuro-visceral and psychiatric manifestations and hyponatremia after surgery. PMID- 28988020 TI - Management of mediastinal parathyroid adenoma via minimally invasive thoracoscopic surgery: Case report. AB - INTRODUCTION: The most common cause of chronic hypercalcemia is primary hyperparathyroidism (PHPT). However, owing to the diverse presentation of hypercalcemia, the diagnosis often goes unnoticed culminating as a continuum of recurrence of symptoms. Nephrolithiasis, decreased bone mineral density and peptic ulcer disease are the main clinical sequelae. Among the causes of PHPT 80% are caused by parathyroid adenomas (PA). However, only rarely, these adenomas are found ectopically. PRESENTATION OF CASE: We present the case of a 66-year-old female with a history of recurrent renal stones and peptic ulcer disease. She was found to have elevated serum calcium and PTH levels. However, subsequent high resolution CT scan of chest and neck failed to demonstrate any abnormality. Therefore, an anterior planar Technetium-99m-sestamibi (MIBI) scintigraphy scan using a single-tracer was done and it identified ectopic anterior mediastinal parathyroid adenoma. The patient was successfully managed with video-assisted thoracoscopic surgery and excision of the mass with follow up calcium level monitoring. DISSCUSSION: An elevated calcium level should prompt a thorough workup, as sometimes it's the only clue to the unrelated and diversified systemic manifestations of hypercalcemia. Hyperparathyroidism due to ectopic adenoma is quite rare and possess a diagnostic and management challenge. CONCLUSION: Symptomatic hypercalcemia and high level of PTH without local PA should alert physicians to search for ectopic locations through imaging. VATS is a safe and effective minimally invasive procedure for the resection of ectopic mediastinal PA and it should be considered as the first line approach for resection of these ectopic tumors. PMID- 28988021 TI - Two concurrent appendiceal neoplasms in an elderly patient: A case report. AB - INTRODUCTION: Acute appendicitis, one of the commonest surgical diagnoses, is rare and more complex presentation in the elderly. Physicians must consider atypical causes appendicitis in this population, which could affect the management of the patient. PRESENTATION OF CASE: An elderly female presented with a two-day history of lower abdominal pain, associated with low-grade fevers and chills. Studies showed leukocytosis and computed tomography (CT) findings consistent with appendicitis. She underwent laparoscopic appendectomy. Intra operatively, the Appendix had an unusual appearance, so a frozen-section was obtained, suggestive of a mucinous neoplasm with grossly clear margins. Despite the possibility that she may require a more extensive cancer operation pending the final Pathology results, the decision was made to complete the operation at this stage, and return at a later date if needed, after completing the patient's work-up with a colonoscopy to rule out any synchronous colonic lesions that could alter her surgical management. Final Pathology revealed both a low-grade appendiceal mucinous neoplasm, as well as a tip carcinoid tumor, both of which were adequately treated with appendectomy alone. DISCUSSION: Physicians treating elderly patients with appendicitis should suspect an atypical etiology, such as appendiceal cancer. Early identification and appropriate pre-operative counseling may alter the surgical management. CONCLUSION: The role and timing of right hemicolectomy in treating appendiceal cancers remain controversial, and should be evaluated on a case by case basis. PMID- 28988022 TI - White matter and schizophrenia: A meta-analysis of voxel-based morphometry and diffusion tensor imaging studies. AB - Voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) are the most implemented methodologies to detect alterations of both gray and white matter (WM). However, the role of WM in mental disorders is still not well defined. We aimed at clarifying the role of WM disruption in schizophrenia and at identifying the most frequently involved brain networks. A systematic literature search was conducted to identify VBM and DTI studies focusing on WM alterations in patients with schizophrenia compared to control subjects. We selected studies reporting the coordinates of WM reductions and we performed the anatomical likelihood estimation (ALE). Moreover, we labeled the WM bundles with an anatomical atlas and compared VBM and DTI ALE-scores of each significant WM tract. A total of 59 studies were eligible for the meta-analysis. WM alterations were reported in 31 and 34 foci with VBM and DTI methods, respectively. The most occurred WM bundles in both VBM and DTI studies and largely involved in schizophrenia were long projection fibers, callosal and commissural fibers, part of motor descending fibers, and fronto-temporal-limbic pathways. The meta-analysis showed a widespread WM disruption in schizophrenia involving specific cerebral circuits instead of well-defined regions. PMID- 28988024 TI - The multidimensional nature of early prosocial behavior: a motivational perspective. AB - A majority of current work indicates that the different types of prosocial behavior in young children (helping, sharing, comforting) are not related to each other. Here, I review recent studies that examined the relations between prosocial actions as well as the antecedents and correlates of the particular domains of prosociality. I argue that in addition to different social-cognitive demands also different motivations are involved in early prosocial action, and that prosociality is thus a concept that encompasses-at least early in development-heterogeneous behaviors and motivations. PMID- 28988025 TI - Towards an objective assessment of motor function in sub-acute stroke patients: Relationship between clinical rating scales and instrumental gait stability indexes. AB - The assessment of walking function alterations is a key issue to design effective rehabilitative interventions in sub-acute stroke patients. Nevertheless, the objective quantification of these alterations remains a challenge. Clinical rating scales are commonly used in clinical practice, but have been proven prone to errors associated to the evaluator subjective perception. On the other hand, instrumental measurement of trunk acceleration can be exploited for an objective quantitative characterization of gait function, but it is not applied in routine clinical practice, because the resulting quantitative indexes have not been related to the clinically information, conventionally provided by the rating scales. To overcome this limitation, the relationship between the indexes, in specific clinical conditions, and rating scale must be better investigated, to support their exploitability in the clinical practice as a fast and reliable screening tool. Thirty-one sub-acute stroke patients (17 with and 14 without cane) participated in the study. All were assessed with 6 rating scales (MI, TCT, MRI, FAC, WHS, CIRS) and 2 functional tests (2MWT and TUG). Sample Entropy (SEN) and Recurrence Quantification Analysis (RQA) in AP, ML and V directions were calculated over 2MWT and walking section of TUG. The influence of assessment task and cane was analysed, as well as correlation of SEN and RQA indexes with clinical rating scales. SEN and RQA on the medio-lateral plane resulted influenced by the use of the cane, while the correlations between indexes and clinical scales showed that SEN and RQA for antero-posterior direction correlate positively with WHS. PMID- 28988023 TI - Acute effects of fine particulate matter constituents on mortality: A systematic review and meta-regression analysis. AB - BACKGROUND: The link between PM2.5 exposure and adverse health outcomes is well documented from studies across the world. However, the reported effect estimates vary across studies, locations and constituents. We aimed to conduct a meta analysis on associations between short-term exposure to PM2.5 constituents and mortality using city-specific estimates, and explore factors that may explain some of the observed heterogeneity. METHODS: We systematically reviewed epidemiological studies on particle constituents and mortality using PubMed and Web of Science databases up to July 2015.We included studies that examined the association between short-term exposure to PM2.5 constituents and all-cause, cardiovascular, and respiratory mortality, in the general adult population. Each study was summarized based on pre-specified study key parameters (e.g., location, time period, population, diagnostic classification standard), and we evaluated the risk of bias using the Office of Health Assessment and Translation (OHAT) Method for each included study. We extracted city-specific mortality risk estimates for each constituent and cause of mortality. For multi-city studies, we requested the city-specific risk estimates from the authors unless reported in the article. We performed random effects meta-analyses using city-specific estimates, and examined whether the effects vary across regions and city characteristics (PM2.5 concentration levels, air temperature, elevation, vegetation, size of elderly population, population density, and baseline mortality). RESULTS: We found a 0.89% (95% CI: 0.68, 1.10%) increase in all cause, a 0.80% (95% CI: 0.41, 1.20%) increase in cardiovascular, and a 1.10% (95% CI: 0.59, 1.62%) increase in respiratory mortality per 10MUg/m3 increase in PM2.5. Accounting for the downward bias induced by studies of single days, the all-cause mortality estimate increased to 1.01% (95% CI: 0.81, 1.20%). We found significant associations between mortality and several PM2.5 constituents. The most consistent and stronger associations were observed for elemental carbon (EC) and potassium (K). For most of the constituents, we observed high variability of effect estimates across cities. CONCLUSIONS: Our meta-analysis suggests that (a) combustion elements such as EC and K have a stronger association with mortality, (b) single lag studies underestimate effects, and (c) estimates of PM2.5 and constituents differ across regions. Accounting for PM mass in constituent's health models may lead to more stable and comparable effect estimates across different studies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO: CRD42017055765. PMID- 28988026 TI - Quantitative Image Restoration in Bright Field Optical Microscopy. AB - Bright field (BF) optical microscopy is regarded as a poor method to observe unstained biological samples due to intrinsic low image contrast. We introduce quantitative image restoration in bright field (QRBF), a digital image processing method that restores out-of-focus BF images of unstained cells. Our procedure is based on deconvolution, using a point spread function modeled from theory. By comparing with reference images of bacteria observed in fluorescence, we show that QRBF faithfully recovers shape and enables quantify size of individual cells, even from a single input image. We applied QRBF in a high-throughput image cytometer to assess shape changes in Escherichia coli during hyperosmotic shock, finding size heterogeneity. We demonstrate that QRBF is also applicable to eukaryotic cells (yeast). Altogether, digital restoration emerges as a straightforward alternative to methods designed to generate contrast in BF imaging for quantitative analysis. PMID- 28988027 TI - GelRed/[G3T]5/Tb3+ hybrid: A novel label-free ratiometric fluorescent probe for H2O2 and oxidase-based visual biosensing. AB - A novel label-free ratiometric fluorescent probe is developed for the detection of H2O2 based on GelRed/[G3T]5/Tb3+ hybrid, in which GelRed (a nucleic acid dye) intercalated into the designed single-stranded DNA [G3T]5 (i.e. GelRed/[G3T]5) acts as a stable build-in reference with red emission and Tb3+ sensitized by [G3T]5 (i.e. [G3T]5/Tb3+) as a sensitive response signal with green fluorescence. With the successive addition of Hg2+ and cysteine (Cys) to GelRed/[G3T]5/Tb3+, the fluorescence of [G3T]5/Tb3+ can be effectively quenched and recovered respectively, while the fluorescence of GelRed/[G3T]5 remains unchangeable. Combined with these properties, we have demonstrated its application for label free ratiometric fluorescence detection of H2O2 with self-calibration. The sensing mechanism is based on the specific reaction between H2O2 and Cys, the resulting disulfide reverses the Cys-mediated fluorescence changes of [G3T]5/Tb3+. This method is further applied to the monitoring of oxidase-related reactions. As the glucose oxidase (GOx)-biocatalyzed oxidation of glucose and the acetylcholine esterase/choline oxidase (AChE/ChOx) cascade yield H2O2, such two biocatalytic processes are successfully examined utilized our proposed method, indicating its potential broad applications in biomedical analysis. In addition, we have also demonstrated its feasibility for oxidase-based visual biosensing, in which only a handheld UV lamp is used. Importantly, coupled with our proposed visual biosensing, a realtime quantitative scanometric assays has been also demonstrated by using a smartphone with easy-to-access color-scanning APP as the detection platform. Compared to traditional methods, the proposed design is cost effective, simple to prepare and easy-to-use without fluorescence labeling or chemical modification. PMID- 28988028 TI - Intensive care admissions among ovarian cancer patients treated with primary debulking surgery and neoadjuvant chemotherapy-interval debulking surgery. AB - OBJECTIVE: Admissions to intensive care units (ICU) are costly, but are necessary for some patients undergoing radical cancer surgery. When compared to primary debulking surgery (PDS), neoadjuvant chemotherapy (NACT) with interval debulking surgery, is associated with less peri-operative morbidity. In this study, we compare rates, indications and lengths of ICU stays among ovarian cancer patients admitted to the ICU within 30days of cytoreduction, either primary or interval. METHODS: A retrospective chart review was performed of patients with stage III-IV ovarian cancer who underwent surgical cytoreduction at two large academic medical centers between 2010 and 2014. Chi square tests, Student t-tests, and Mann-U Whitney tests were used. RESULTS: A total of 635 patients were included in the study. There were 43 ICU admissions, 7% of patients. Compared to NACT, a higher percentage of PDS patients required ICU admission, 9.4% vs 3.9% of patients (P=0.004). ICU admission indications did not vary between PDS and NACT patients. NACT patients admitted to the ICU had comparable mean surgical complexity scores to those PDS patients admitted to the ICU, 6.2 (95%CI 5.3-7.1) vs 4.5 (95%CI 3.1 6.0) (P=0.006). Length of ICU admission did not vary between groups, PDS 2.7days (95%CI 2.3-3.2) vs 3.5days (95%CI 1.5-5.6) for NACT (P=0.936). CONCLUSIONS: The rate of ICU admissions among patients undergoing PDS is higher than for NACT. Among patients admitted to the ICU, indications for admission, length of stay and surgical complexity were similar between patients treated with NACT and PDS. PMID- 28988029 TI - Management of male hypogonadism and testosterone therapy: European Association of Urology position statement on the role of the urologist. PMID- 28988030 TI - Sub-lethal viral exposure and growth on drought stressed host plants changes resource allocation patterns and life history costs in the Speckled Wood butterfly, Pararge aegeria. AB - This study investigated the interactive effects of growth on drought stressed host plants and pathogen challenge with the baculovirus Autographa californica nucleopolyhedrovirus (AcMNPV) on survival and fitness-related traits using the Speckled Wood butterfly, Pararge aegeria (L.). Exposure to AcMNPV significantly reduced survival to pupation. For surviving larvae, sub-lethal infection significantly decreased daily mass acquisition rates and pupal mass. Growth on drought stressed plants increased daily mass acquisition rates resulting in heavier pupae, and increased resource allocation to adult reproduction. The interaction between host plant drought and viral exposure resulted in different resource allocation strategies, and thus different growth trajectories, between larvae. This in turn resulted in significantly different allometric relationships between larval mass (at inoculation) and both development time and investment in flight muscles. For larvae with relatively lighter masses there was a cost of resisting infection when growth occurred on drought stressed host plants, both within the larval stage (i.e. longer larval development times) and in the adult stage (i.e. lower investment in flight muscle mass). This multi-factor study highlights several potential mechanisms by which the complex interplay between low host plant nutritional quality due to drought, and pathogen exposure, may differentially influence the performance of P. aegeria individuals across multiple life stages. PMID- 28988032 TI - Expanding the genetic tool box for Cupriavidus necator by a stabilized L-rhamnose inducible plasmid system. AB - The Gram negative bacterium Cupriavidus necator is well known for the accumulation of poly(3-hydroxybutyrate) and its fast lithoautotrophic growth, leading in high cell densities. Although the host was engineered for the heterologous production of diverse chemicals and biopolymers in recent years, tool box of stabilized inducible expression systems is still limited. To avoid plasmid loss during fermentation processes and to allow expression of complex proteins, a tunable L-rhamnose inducible system was established and characterized using enhanced green fluorescent protein (eGFP). The construct was stabilized by a previously established partitioning system. An increase of fluorescence signal intensity in different media was shown with inducer concentrations up to 11mM L rhamnose. The strongest effects were measured at quite low concentrations - high tunability was observed between 0 and 0.4-1mM (depending on the medium used). Expression is tightly regulated and could be increased over 140-fold in complex medium and approximately 60-fold in minimal medium due to induction with 11mM L rhamnose. Varying induction times were characterized regarding growth behavior and expression pattern, taking into consideration problems that may arise during expression of toxic proteins. The novel plasmid expands the tool box for engineering the highly flexible production host C. necator. PMID- 28988031 TI - Metabolic engineering of Escherichia coli for production of valerenadiene. AB - Valeriana officinalis is a medicinal herb which produces a suite of compounds in its root tissue useful for treatment of anxiety and insomnia. The sesquiterpene components of the root extract, valerenic acid and valerena-1,10-diene, are thought to contribute to most of the observed anxiolytic of Valerian root preparations. However, valerenic acid and its biosynthetic intermediates are only produced in low quantities in the roots of V. officinalis. Thus, in this report, Escherichia coli was metabolically engineered to produce substantial quantities of valerena-1,10-diene in shake flask fermentations with decane overlay. Expression of the wildtype valerenadiene synthase gene (pZE-wvds) resulted in production of 12MUg/mL in LB cultures using endogenous FPP metabolism. Expression of a codon-optimized version of the valerenadiene synthase gene (pZE-cvds) resulted in 3-fold higher titers of valerenadiene (32MUg/mL). Co-expression of pZE-cvds with an engineered methyl erythritol phosphate (MEP) pathway improved valerenadiene titers 65-fold to 2.09mg/L valerenadiene. Optimization of the fermentation medium to include glycerol supplementation enhanced yields by another 5.5-fold (11.0mg/L valerenadiene). The highest production of valerenadiene resulted from engineering the codon-optimized valerenadiene synthase gene under strong Ptrc and PT7 promoters and via co-expression of an exogenous mevalonate (MVA) pathway. These efforts resulted in an E. coli production strain that produced 62.0mg/L valerenadiene (19.4mg/L/OD600 specific productivity). This E. coli production platform will serve as the foundation for the synthesis of novel valerenic acid analogues potentially useful for the treatment of anxiety disorders. PMID- 28988033 TI - Evidence of microglial activation following exposure to serum from first-onset drug-naive schizophrenia patients. AB - Abnormal activation of brain microglial cells is widely implicated in the pathogenesis of schizophrenia. Previously the pathophysiology of microglial activation was considered to be intrinsic to the central nervous system. We hypothesised that due to their perivascular localization, microglia can also be activated by factors present in circulating blood. Through application of high content functional screening, we show that peripheral blood serum from first onset drug-naive schizophrenia patients is sufficient to provoke microglial cell signalling network responses in vitro which are indicative of proinflammatory activation. We further explore the composition of the serum for the presence of analytes, with the potential to activate microglia, and the utility of the resultant microglial cellular phenotype for novel drug discovery. PMID- 28988034 TI - The physical forces mediating self-association and phase-separation in the C terminal domain of TDP-43. AB - The TAR DNA-binding protein of 43kDa (TDP-43) has been identified as the main component of amyotrophic lateral sclerosis (ALS) cytoplasmic inclusions. The link between this proteinopathy and TDP-43's intrinsically disordered C-terminal domain is well known, but recently also, this domain has been shown to be involved in the formation of the membraneless organelles that mediate TDP-43's functions. The mechanisms that underpin the liquid-liquid phase separation (LLPS) of these membraneless organelles undergo remain elusive. Crucially though, these factors may be the key to understanding the delicate balance between TDP-43's physiological and pathological functions. In this study, we used nuclear magnetic resonance spectroscopy and optical methods to demonstrate that an alpha-helical component in the centre (residues 320-340) of the C-terminal domain is related to the protein's self-association and LLPS. Systematically analysing ALS-related TDP 43 mutants (G298S, M337V, and Q331K) in different buffer conditions at different temperatures, we prove that this phase separation is driven by hydrophobic interactions but is inhibited by electrostatic repulsion. Based on these findings, we rationally introduced a mutant, W334G, and demonstrate that this mutant disrupts LLPS without disturbing this alpha-helical propensity. This tryptophan may serve as a key residue in this protein's LLPS. PMID- 28988035 TI - Coumarin based colorimetric and fluorescence on-off chemosensor for F-, CN- and Cu2+ ions. AB - (E)-4-Chloro-3-[{2-(4-nitrophenyl)hydrazono}methyl]-2H-chromen-2-one (C), a coumarin derivative has been studied toward its ion sensing properties for F-, CN and Cu2+. A proton-transfer mechanism for F- sensing has been deduced with the help of 1H NMR titration alongwith from the changes in the absorption and emission spectra of C in the presence of F-. C formed 1:1 stoichiometric complex with each of these analytes. Sensing of C toward Cu2+ is poor, but interestingly in the presence of F-or CN- the sensing ability of Cu2+ gets enhanced many folds, and C can act as F-or CN- mediated off-on sensor for Cu2+. Moreover, colorimetric strip (pre-coated with the coumarin derived compound) tests for F-and CN- from their DMSO solution at high temperature (~100 degrees C) opens up the door for easiest naked eye recognition and distinction of these ions, and also for naked eye detection of F- and CN- from its aqueous solution at high temperature (~100 degrees C). PMID- 28988036 TI - Drought tolerance of selected bottle gourd [Lagenaria siceraria (Molina) Standl.] landraces assessed by leaf gas exchange and photosynthetic efficiency. AB - Successful cultivation of bottle gourd in arid and semi-arid areas of sub-Saharan Africa and globally requires the identification of drought tolerant parents for developing superior genotypes with increased drought resistance. The objective of this study was to determine the level of drought tolerance among genetically diverse South African bottle gourd landraces based on leaf gas exchange and photosynthetic efficiency and identify promising genotypes for breeding. The responses of 12 bottle gourd landraces grown in glasshouse under non-stressed (NS) and drought-stressed (DS) conditions were studied. A significant genotype x water regime interaction was observed for gs, T, A, A/Ci, IWUE, WUEins, Fm', Fv'/Fm', FPSII, qP, qN, ETR, ETR/A and AES indicating variability in response among the studied bottle gourd landraces under NS and DS conditions. Principal component analysis identified three principal components (PC's) under drought stress condition contributing to 82.9% of total variation among leaf gas exchange and chlorophyll fluorescence parameters measured. PC1 explained 36% of total variation contributed by gs, T, F0', Fm', Fv'/Fm' and qN, while PC2 explained 28% of the variation and highly correlated with A, A/Ci, IWUE, WUEins ETR/A and AES. PC3 explained 14% of total variation contributed by FPSII, qP and ETR. Principal biplot analysis allowed the identification of drought tolerant genotypes such as BG-27, BG-48, BG-58, BG-79, BG-70 and BG-78 which were grouped based on high gs, A, Fm'Fv'/Fm', qN, ETR/A and AES under DS condition. The study suggests that the identified physiological traits could be useful indicators in the selection of bottle gourd genotypes for increased drought tolerance. PMID- 28988037 TI - Cost-effectiveness of methods in personalized medicine. Results of a decision analytic model in patients with acute myeloid leukemia with normal karyotype. AB - BACKGROUND: During the last years, molecular genetic data are increasingly used as prognostic and predictive factors in acute myeloid leukemia (AML). The molecular genetic profile permits a rapid risk categorization and beyond that a prediction of differential treatment efficacy of post-remission chemotherapy versus an allogeneic hematopoietic cell transplantation (HCT) in specific subgroups. METHODS: The aim of this study was to evaluate cost-effectiveness of two different strategies of risk categorization (conventional cytogenetic diagnostics (CCD) versus molecular genetic diagnostics (MGD)) in patients with AML, using a decision-analytic state-transition model. The model is run as (Monte Carlo) microsimulation in which individuals pass through in cycles with a cycle length of one month and a time horizon of ten years. FINDINGS: Results show that on average, individuals within the MGD group generated about US$ 32,000 higher costs but survived about seven months longer than individuals within the CCD group. This leads to an Incremental Cost-Effectiveness Ratio (ICER) of about US$ 4928 per survived month. INTERPRETATION: With a GDP (Gross Domestic Product) of US$ 26,467 (? 33,630) per capita in Germany in 2012, the base-case ICER of US$ 4928 per survived month projected to US$ 59,136 per survived year is in between the simple GDP and the three times GDP per capita. PMID- 28988038 TI - Innate immune transcriptomic evaluation of PBMC isolated from sheep after infection with E. ruminantium Welgevonden strain. AB - Heartwater is a tick-borne non-infectious fatal disease of wild and domestic ruminants caused by the bacterium Ehrlichia ruminantium, transmitted by Amblyomma ticks. Although there is evidence that interferon-gamma (IFN-gamma) controls E. ruminantium growth and that cellular immune responses could be protective, an effective recombinant vaccine for this disease is lacking. An overall analysis of which immune pathways are up- or down-regulated in sheep peripheral blood mononuclear cells is expected to lead to a better understanding of the global immune response of sheep to E. ruminantium infection. Therefore, a systems biology oriented approach following the infection with E. ruminantium was investigated from peripheral blood mononuclear cells to aid recombinant vaccine development. In this study, heartwater naive sheep were infected and challenged by allowing E. ruminantium infected ticks to feed on them. After primary infection, all the animals were treated with antibiotic during the resulting febrile response. Blood was collected daily for E. ruminantium detection by qPCR (pCS20 assay). The pCS20 assay only detected the pathogen in the blood one day prior to and during the febrile stage of infection confirming infection of the sheep. IFN-gamma real-time PCR indicated that this cytokine was expressed at specific time points: post infection, during the febrile stage of the disease and after challenge. These were used as a guide to select samples for transcriptome sequencing. This paper focuses on transcripts that are associated with innate activating pathways that were identified to be up- and down-regulated after primary infection and the subsequent challenge. These included the CD14 monocyte marker, toll-like receptor (TLR), nod-like receptor, chemokine, cytosolic and cytokine-cytokine interaction receptor pathways. In particular, TLR4, TLR9 and CD14 were activated together with DNA detection pathways, suggesting that vaccine formulations may be improved if CpG motifs and lipopolysaccharides are included. This data indicates that innate immune activation, perhaps by using adjuvants, should be an important component for consideration during future heartwater recombinant vaccine development. PMID- 28988039 TI - Cathelicidin modulates synthesis of Toll-like Receptors (TLRs) 4 and 9 in colonic epithelium. AB - Cathelicidin are innate antimicrobial peptides with broad immunomodulatory functions; however, their role in regulating intestinal defenses is not well characterized. This study aimed to investigate the role of cathelicidin modulating expression of Toll-like receptors (TLRs) 4 and 9 in colonic epithelium in response to bacterial patterns. We demonstrated herein that intestinal epithelial cells, when primed by bacterial lipopolysaccharide (LPS), responded to cathelicidin by increased transcription and protein synthesis of TLR4. This cathelicidin-induced response required the interaction of LPS-TLR4 and activation of MAPK signalling pathways. However, cathelicidin blocked TLR9 responses induced by TLR9 ligand CpG oligodeoxynucleotide (CpG ODN) in these colonic epithelial cells. Modulations of TLRs triggered by cathelicidin in intestinal epithelium occurred mainly in the apical compartment of intestinal cells. Activation of TLR4 by ligands in combination with cathelicidin promoted CXCL8 chemokine secretion and epithelial antimicrobial defenses against Escherichia coli. We concluded that cathelicidin selectively modulated synthesis of TLR4 and 9 in intestinal epithelium, but only when cells were exposed to virulence factors, mostly from apical surfaces. Enhanced TLR4 expression promoted by cathelicidin in intestinal epithelium may be crucial for controlling enteric infectious diseases. PMID- 28988040 TI - Johne's disease in cattle: an in vitro model to study early response to infection of Mycobacterium avium subsp. paratuberculosis using RNA-seq. AB - Johne's disease is a chronic granulomatous enteritis caused by Mycobacterium avium subsp. paratubercolosis (MAP) which affects ruminants worldwide and has a significant economic impact. MAP has also been associated with human Crohn's disease, although this connection is not well established. MAP is highly adapted for survival within host macrophages and prevents macrophage activation, blocks phagosome acidification and maturation, and attenuates presentation of antigens to the immune system. The consequence is a very long silent infection before clinical signs are observed. The present work examined the transcriptome of bovine monocyte-derived macrophages (MDM) infected with the L1 strain of MAP at 2h, 6h and 24h post infection using RNA-seq. Pathway over-representation analysis of genes differentially expressed between infected vs. control MDM identified that immune related pathways were affected. Genes belonging to the cytokine cytokine receptor interaction pathway and members of the JAK-STAT pathway, which is involved in the regulation of immune response, were up-regulated. However, in parallel inhibitors of immune functions were activated, including suppressor of cytokine signaling (SOCS) and cytokine-inducible SH2-containing protein (CISH), which most likely suppresses IFNgamma and the JAK/STAT signaling cascade in infected MDM, which may favour MAP survival. After exposure, macrophages phagocytise pathogens, activate the complement cascade and the adaptive immune system through the antigen presentation process. However, data presented here suggest that genes related to phagocytosis and lysosome function are down regulated in MAP infected MDM. Genes of MHC class II and complement pathway were also down-regulated. This study therefore shows that MAP infection is associated with changes in expression of genes related to the host immune response that may affect its ability to survive and multiply inside the host cell. PMID- 28988041 TI - Recombinant small glutamine-rich tetratricopeptide repeat-containing protein of Leishmania infantum: Potential vaccine and diagnostic application against visceral leishmaniasis. AB - Different Leishmania proteins have been evaluated in order to find a potential vaccine candidate or diagnostic marker capable of providing long lasting protection against infection or helping to identify infected mammalian hosts, respectively. However, just few molecules have fulfilled all the requirements to be evaluated. In the current study, we evaluated the prophylactic and diagnostic value against visceral leishmaniasis (VL) of a small glutamine-rich tetratricopeptide repeat-containing (SGT) protein from Leishmania infantum species. In a first step, the immune response elicited by the immunization using the recombinant protein (rSGT) plus saponin was evaluated in BALB/c mice. Immunized animals had a low parasitism in all evaluated organs. They developed a specific Th1 immune response, which was based on protein-specific production of IFN-gamma, IL-12 and GM-CSF, and a humoral response dominated by antibodies of the IgG2a isotype. Both CD4+ and CD8+ T cells contributed to the IFN-gamma production, showing that both T cell subtypes contribute to the resistance against infection. Regarding its value as a diagnostic marker, rSGT showed maximum sensitivity and specificity to serologically identify L. infantum infected dog and human sera. No cross-reactivity with sera from humans or dogs that had other diseases was found. Although further studies are necessary to validate these findings, data showed here suggest immunogenicity of rSGT and its protective effect against murine VL, as well as its potential for the serodiagnosis of human and canine VL. PMID- 28988042 TI - Improved photo-induced charge carriers separation through the addition of erbium on TiO2 nanoparticles and its effect on photocatalytic degradation of rhodamine B. AB - ErxTi1-xO2 nanocomposites was prepared by a simple sol-gel method with various proportion of erbium viz., x=0.02, x=0.04, x=0.06, x=0.08 and x=0.10. The prepared nanocomposites were studied using XRD, UV-Vis DRS, Raman spectra, HR SEM, EDS, TEM, PL and impedance spectroscopy. XRD revealed that modified TiO2 nanocomposites possessed only the anatase phase with crystallite sizes of about 8.1 to 12.7nm and which is well consistent with TEM analysis. It is seen that erbium ion exist in the nanocomposites based on the analysis of EDS. HR-SEM analysis revealed that the ErxTi1-xO2 nanocomposites are spherical in shape with size between 10 and 20nm. The amount of erbium remarkably affects the structural, optical and electrical properties. Loading erbium could produce 4f energy levels between valence and conduction bands thus narrowing optical band gap and generates visible absorption peaks. It was found that erbium modified TiO2 nanocomposites induced a shift in Raman. The enhancement of life time of charge carriers was observed on erbium inclusion. PMID- 28988043 TI - Metabolic signatures of bisphenol A and genistein in Atlantic salmon liver cells. AB - Screening has revealed that aquafeeds with high inclusion of plant material may contain small amounts of endocrine disrupting agricultural pesticides. In this work, bisphenol A (BPA) and genistein (GEN) were selected as model endocrine disrupting toxicants with impact on DNA methylation in fish. Atlantic salmon hepatocytes were exposed in vitro to four concentrations of BPA and GEN (0.1, 1.0, 10 and 100 MUM) for 48 h. Toxicity endpoints included cytotoxicity, global DNA methylation, targeted transcriptomics and metabolomic screening (100 MUM). GEN was not cytotoxic in concentrations up to 100 MUM, whereas one out of two cell viability assays indicated a cytotoxic response to 100 MUM BPA. Compared to the control, significant global DNA hypomethylation was observed at 1.0 MUM BPA. Both compounds upregulated cyp1a1 transcription at 100 MUM, while estrogenic markers esr1 and vtg1 responded strongest at 10 MUM. Dnmt3aa transcription was downregulated by both compounds at 100 MUM. Metabolomic screening showed that BPA and GEN resulted in significant changes in numerous biochemical pathways consistent with alterations in carbohydrate metabolism, indicating perturbation in glucose homeostasis and energy generation, and glutamate metabolism. Pathway analysis showed that while the superpathway of methionine degradation was among the most strongly affected pathways by BPA, GEN induced changes to uridine and pyrimidine biosynthesis. In conclusion, this mechanistic study proposes metabolites associated with glucose and glutamate metabolism, glucuronidation detoxification, as well as cyp1a1, vtg1, esr1, ar, dnmt3aa, cdkn1b and insig1 as transcriptional markers for BPA and GEN exposure in fish liver cells. PMID- 28988044 TI - Adversity and persecutory ideation: A moderated mediational model. AB - Adversity has been identified as an important factor in models of psychopathology and can help in understanding persecutory ideation, although potential moderators and mediators for adult psychopathology have not been sufficiently examined. Experiential avoidance (EA) and Self-esteem (SE) are relevant factors to understand how adversity leads to persecutory ideation. This study hypothesized that adversity would be associated with persecutory ideation through heightened EA, and that this association would be strengthened in individuals with a discrepant high SE. Participants with persecutory ideation (n = 52), with depression (n = 35) and healthy controls (n = 51) were assessed with the Trauma History Screen, the Paranoia and Deservedness Scale, and the Beck Depression Inventory. A SE discrepancy index was calculated subtracting the normalized explicit SE score from the normalized implicit SE score (measured by a version of a Go/No-go association task). Our analysis revealed that adversity was associated with higher levels of paranoia and was mediated by EA. In addition, we found that the relationship between adversity and EA was moderated by SE discrepancy. Identification of moderating and mediating variables allows for increased understanding of persecutory ideation and the processes that should be targeted in the course of recovery. PMID- 28988045 TI - Prescribing practices in Southeastern Europe - focus on benzodiazepine prescription at discharge from nine university psychiatric hospitals. AB - There is much concern about the widespread long-term use of benzodiazepines. Our manuscript addressed its use in the region of Southeastern Europe, which seems extensive, but insufficiently explored. At nine university psychiatric hospitals (Croatia, Macedonia and Serbia), we retrospectively analyzed discharge summary documents to find the prevalence of discharge benzodiazepine prescriptions and the prescribed benzodiazepine doses. This study included 1047 adult subjects and showed that 81.9% of them had benzodiazepines prescribed in the discharge summary document, with high mean daily dose of around 5mg lorazepam equivalents. Factors associated with the prescriptions were exclusively clinical factors (diagnosis of schizophrenia spectrum disorders, more lifetime hospitalizations, psychiatric comorbidity, co-prescription of antidepressant or mood stabilizer, shorter duration of the hospitalization), while socio-demographic factors were not found to influence benzodiazepine discharge prescriptions. Similarly, factors which influenced the prescription of higher daily benzodiazepine dose were more lifetime psychiatric hospitalizations and co-prescription of antidepressant or mood stabilizer, as well as the diagnosis of mental/behavioral disorders due to substance use and co-prescribed antipsychotic. Our data are emphasizing an urgent need for guidelines and improved education of both health care professionals and patients, in order to prevent long term benzodiazepine (mis)use and related side effects. PMID- 28988046 TI - Testing the Trower and Chadwick model of paranoia: Is 'poor-me' and 'bad-me' paranoia acting as a defence? AB - The study tested the predicted differences in phenomenology (self-esteem and depression) and insecurity of the subgroups of paranoia proposed by the Trower and Chadwick (1995) model of paranoia. Thirty-two inpatients experiencing persecutory delusions were assigned to either the poor me or bad me paranoid group. Questionnaire assessment of depression and self-esteem were conducted. A Dot Probe task measured detection latency (reaction time) to poor me words, bad me words and neutral words. The poor me and bad me groups displayed the predicted phenomenological differences. The dot probe task did not support the predicted insecurities of the Trower and Chadwick model, but unexpected significant results for the poor me subgroup may offer support for an alternative explanation of paranoia as an unstable phenomenon. PMID- 28988047 TI - The identification of Lynch syndrome in Congolese colorectal cancer patients. AB - BACKGROUND: We aimed to investigate the prevalence of Lynch syndrome as one of hereditary causes of colorectal cancer (CRC) among young Congolese individuals affected by the CRC, and to define methods for diagnosis in Congo Brazzaville. METHODS: We conducted a transversal cohort study of 34 patients having a CRC with a family history for a period of eight years. They were selected among 89 CRCs of any type from the Bethesda guidelines criteria combined with pedigrees. Mismatch repair (MMR) genes alterations were researched by immunohistochemistry (IHC). RESULTS: We identified with the Bethesda criteria a total of 38.2% (34/89) patients having familial CRC with a confidence interval (CI) of 95%=[0.34-0.41]. Only 14.7% (5/34) 95% CI=[0.34-2.32] patients showed MMR immunodeficiency involving firstly MLH1 protein then MSH2 protein. These data account for 5.6% (5/89) 95% CI=[0.15-0.33] of patients affected by Lynch syndrome with an earlier median age of 35 years (range 20 to 47 years). CONCLUSION: The prevalence of Lynch syndrome found in Brazzaville is comparable to that is found in northern countries. The combined Bethesda guidelines, pedigree and IHC is an accessible and good alternative method for the positive diagnosis of Lynch syndrome in current practice in Congo. PMID- 28988048 TI - Effect of hydraulic retention time on microbial community in biochemical passive reactors during treatment of acid mine drainage. AB - The effect of hydraulic retention time (HRT) on the microbial community during acid mine drainage (AMD) treatment was investigated. Physicochemical and molecular (illumina and qPCR) analyses were performed on reactive mixtures collected from seven bioreactors in three-operation period (8, 17 and 36weeks). Long HRT (4day) favored the relative abundance of SRB, causing the increase of residual sulfides and short HRT (1day) affected the anaerobic conditions of the bioreactors and favored the presence the acidophilic chemolithotrophic microorganisms. Besides qPCR indicated that genes related to cellulose degradation were present in low copy numbers and were affected by the HRT. Finally, environmental factors (pH, organic source, metal sulfides, and sulfate concentrations) had significant impact on relative abundance of the phylogenetic lineages, rather than the types of lineages present in the reactive mixture. The findings of this study indicate that HRT affects the stability of passive bioreactors and their microbial communities. PMID- 28988049 TI - Development of a thermo-stable and recyclable magnetic nanobiocatalyst for bioprocessing of fruit processing residues and D-allulose synthesis. AB - The aim of the study was to covalently immobilize Smt3-D-psicose 3-epimerase onto functionalized iron oxide magnetic nanoparticles. After immobilization, Km of the immobilized enzyme increased, however, Vmax was nearly the same as that of its free form, indicating that immobilization has no detrimental effects on its catalytic output. The covalent immobilization caused a reduction in the deactivation rate constant (kd) values leading to 4-5 fold enhancement in its half-life at 50-65 degrees C, indicating significant thermal stability of the iron-enzyme nanobioconjugate. The immobilized enzyme showed excellent storage stability by losing only 20% activity even after 60days of storage at 4 degrees C. The immobilized enzyme retained up to 90% of its initial activity even after 10 consecutive cycles of catalyzing D-fructose epimerization reactions. Thus, after immobilization the enzyme exhibited remarkable improvements in thermal tolerance, storage stability and recycling efficiency, useful for development of industrially exploitable process for D-allulose production. PMID- 28988050 TI - A comprehensive mechanistic model for simulating algal-bacterial growth dynamics in photobioreactors. AB - A comprehensive mechanistic model with state of the art understanding and assumptions is presented to simulate major processes in a photobioreactor for describing the algal-bacterial growth dynamics. The model includes a total of 37 state variables that broadly cover all the essential physiological and physico chemical processes in such a system. Model parameters are first calibrated with batch experimental data, and thereafter, extensive validation of the model is carried with long term independent experimental data in diverse conditions. The developed model is able to capture the complex system behavior with reasonable accuracy. Also, the comprehensive mathematical formulation with realistic assumptions make this model a valuable tool for gaining better insights into the complex system behavior. PMID- 28988051 TI - Influence of lime and struvite on microbial community succession and odour emission during food waste composting. AB - Lime addition as well as formation of struvite through the addition of magnesium and phosphorus salts provide good pH buffering and may reduce odour emission. This study investigated the odour emission during food waste composting under the influence of lime addition, and struvite formation. Composting was performed in 20-L reactors for 56days using artificial food waste mixed with sawdust at 1.2:1 (w/w dry basis). VFA was one of the most important odours during food waste composting. However, during thermophilic phase, ammonia is responsible for max odour index in the exhaust gas. Trapping ammonia through struvite formation significantly reduced the maximum odour unit of ammonia from 3.0*104 to 1.8*104. The generation and accumulation of acetic acid and butyric acid led to the acidic conditions. The addition of phosphate salts in treatment with struvite formation improved the variation of total bacteria, which in turn increased the organic decomposition. PMID- 28988052 TI - Comparison of varying operating parameters on heavy metals ecological risk during anaerobic co-digestion of chicken manure and corn stover. AB - In this study, the potential ecological risk of heavy metals (Mn, Zn, Cu, Ni, As, Cd, Pb, Cr) accumulation from anaerobic co-digestion of chicken manure (CM) and corn stover (CS) was evaluated by comparing different initial substrate concentrations, digestion temperatures, and mixture ratios. Results showed that the highest volumetric methane yield of 20.3+/-1.4L/L reactor was achieved with a CS:CM ratio of 3:1 (on volatile solid basis) in mesophilic solid state anaerobic digestion (SS-AD). Although co-digestion increased the concentrations of all tested heavy metals and the direct toxicity of some heavy metals, the potential ecological risk index indicated that the digestates were all classified as low ecological risk. The biogasification and risk variation of heavy metals were affected by the operating parameters. These results are significant and should be taken into consideration when optimizing co-digestion of animal manure and crop residues during full-scale projects. PMID- 28988053 TI - Biochar accelerates PAHs biodegradation in petroleum-polluted soil by biostimulation strategy. AB - Sawdust and wheat straw biochars prepared at 300 degrees C and 500 degrees C were applied to petroleum-polluted soil for an 84-day incubation to estimate their effectiveness on polycyclic aromatic hydrocarbons (PAHs) removal. Biochars alone were most effective at reducing PAHs contents. However, adding biochar to soils in company with NaN3 solution resulted in a decreasing trend in terms of PAHs removal, which was even lower than treatment CK without biochar. Moreover, it was discovered by PCR-DGGE files and sequencing analysis that the predominant bacterial diversity slightly decreased but the abundance of some specific taxa, including PAHs degraders, was promoted with biochar input. These results highlighted the potential of biochar application on accelerating PAHs biodegradation, which could be attributed to the properties of biochars that benefit for making the amended soil a better habitat for microbes. The impacts of biochar preparation and pollutants nature on PAHs removal were also determined. Significant reduction in the PAHs contents was detected when adding biochar prepared at a high temperature (500 degrees C), while the feedstocks of biochar showed little effect on PAHs removal. Due to the high hydrophobicity of aromatic rings, high-molecular weight PAHs were found much more resistant to microbial degradation in comparison with low-molecular weight PAHs. PMID- 28988054 TI - Titania nanowires functionalized polyester fabrics with enhanced photocatalytic and antibacterial performances. AB - Flexible organic fabrics coated with titania find wide applications in pollutant degradations and antibiosis. Because of the enhanced charge separations, TiO2 with one-dimensional nanostructures exhibits photocatalytic activity superior to that of nanoparticulate films; however, only the later has been achieved on organic substrates through commonly sol-gel techniques till now. In this study, radially aligned TiO2 nanowires were precipitated on polyester fabrics through multi-steps of surface roughening, sol-gel TiO2 seeding, hydrogen titanate nanobelts precipitation, and finally sulfuric acid treatment. Both mesoporous anatase TiO2 nanowires and single-crystalline rutile TiO2 nanorods have been achieved, which, together with some unchanged titanate nanobelts, exhibited an overall narrowed band gap of ca. 2.50eV. The TiO2 nanowires on flexible PET fabrics showed higher photocatalytic activity towards degradations of not only rhodamine B in water but also toluene gas in air under UV light illumination, when compared with either TiO2 nanotube array or commercial Degussa P25 nanoparticulate films on metallic Ti substrates. Remarkable sterilization of E. coli and S. epidermidis under visible light irradiation was also achieved. The excellent photocatalytic and antibacterial performances were attributed to the unique mixed 1D nanostructures, phase junctions, abundant surface hydroxyl groups, and the narrowed band gap. PMID- 28988055 TI - A phosphorylethanolamine-functionalized super-hydrophilic 3D graphene-based foam filter for water purification. AB - A phosphorylethanolamine-functionalized graphene foam (PNGF) has been proposed as an active filtration material for the capture and removal of heavy metal ions in water. Benefiting from its abundant hydrophilic portion of oxygen, nitrogen and phosphorus groups, the PNGF is super-hydrophilic. The selected heavy metal ions, Pb(II) and Cd(II), could be rapidly and efficiently absorbed within 10min using the PNGF through a filtration model, which is obviously less time compared with the several hours or even longer time when employing the traditional shaking or stirring model. In addition, the used PNGF filters can be easily reused after a simple, low-cost detachment using HCl to remove the heavy metals, providing a new approach for water purification. PMID- 28988056 TI - Synthesis of magnetic orderly mesoporous alpha-Fe2O3 nanocluster derived from MIL 100(Fe) for rapid and efficient arsenic(III,V) removal. AB - A calcination time regulation method has been unprecedentedly used to adjust the orderly meso-structure of novel alpha-Fe2O3 nanoclusters derived from MIL-100(Fe) (MIL: Materials of Institute Lavoisier). The as-synthesized magnetic orderly mesoporous alpha-Fe2O3 nanoclusters were characterized by XRD, SEM, TEM, TGA, N2 adsorption-desorption isotherms, VSM, Zeta potential, FTIR and XPS. The 6h calcinated alpha-Fe2O3 nanocluster exhibited the optimal properties, including the high specific surface area and the orderly mesoporous properties, which facilitate the arsenic(III,V) adsorption capacity. The maximum adsorption capacities of As(III) and As(V) were 109.89 and 181.82mgg-1, respectively, and adsorption equilibrium can be reached just within 30min. The kinetics intra particle diffusion model and adsorption isotherms reveal that the adsorption rate is controlled by pore diffusion and the adsorption process belongs to Langmuir monolayer adsorption. These results indicate that the orderly mesoporous structure of alpha-Fe2O3 nanoclusters plays a key role in rapid and efficient adsorption for arsenic(III,V). Meanwhile, adsorption mechanism verifies that arsenic can react with active sites (Fe-OH) to form complexes by Fe-O-As bond. Moreover, alpha-Fe2O3 nanocluster can be separated easily due to its excellent magnetism. Above all, the magnetism orderly mesoporous alpha-Fe2O3 nanocluster is a promising adsorbent for emergent treatment of arsenic in practice. PMID- 28988057 TI - Role of manganese dioxide in the recovery of oxide-sulphide zinc ore. AB - In this article, the role of MnO2 in the recovery of oxide-sulphide zinc ore discussed. Through adopting various modern analysis techniques (such as X-ray diffraction pattern, X-ray photoelectron spectroscopy, scanning electron microscope, energy dispersive X-ray analysis, and fourier transform infrared spectroscopy), the function and mechanism of MnO2 during the phase transformation process is found out. Thermodynamic mechanisms involved in the phase transformation process with or without addition of manganese dioxide investigated by exploiting the Equilib module of FactSage. What's more, XRD patterns, XPS spectra and SEM-EDAX analyses of zinc calcines verify well the calculations of FactSage. Results reveal that the addition of MnO2 will produce an aggregation of ZnMn2O4, a valuable energy material, while roasting on its own, results in generating undesirable Zn2SiO4, the oxidation degree being relatively low. Moreover, XRD pattern of zinc calcine and FT-IR spectrum of yellow product collected in the calcination process prove that the sulphur-fixing value of the additive MnO2, which can promote transforming to the elemental sulphur. The volatile S can be collected through a simple guiding device. In this process, the emission of SO2 effectively avoids, thus MnO2 deems as a potential additive in the recovery of oxide-sulphide zinc ore. PMID- 28988058 TI - The down-regulation of casein kinase 1 alpha as a host defense response against infectious bursal disease virus infection. AB - Infectious bursal disease virus (IBDV) is an important immunosuppressive virus of chickens. Although the gene functions of IBDV have been well characterized, the host responses during IBDV infection remain much poor. In the present study, casein kinase 1 alpha (CK1alpha), a novel VP2-associated protein, was down regulated during IBDV replication in DF1 cells. Further experiments showed that siRNA-mediated knockdown of CK1alpha inhibited IBDV replication, while overexpression of CK1alpha promoted IBDV growth. Finally, we revealed that the effects of CK1alpha expression level on IBDV replication were involved in the negative regulation of CK1alpha on type I interferon receptor (IFNAR1), because ubiquitination assay analyses demonstrated that CK1alpha could promote the ubiquitination of IFNAR1, thereby affecting the stability of this receptor. In conclusion, down-regulation of CK1alpha during IBDV infection as a host defense response increased abundance of IFNAR1, which in turn enhanced an inhibitory effect on IBDV replication. PMID- 28988059 TI - Ionizing diagnostic radiation exposure in patients with Crohn's disease: A retrospective study in a medium hospital and its predictive factors. AB - INTRODUCTION: It is estimated that diagnostic medical radiation exposure may be responsable for 0.5-2% of cancers worldwide. Because of the relapsing course of Crohn's disease (CD), these patients usually requiere multiple ionizing radiation test. OBJECTIVE: Stimating the total cumulative effective dose received by our CD patients and identifying the risk factors associated with the exposure to a cumulative effective dose due to the disease (CEED) > 50mSv. MATERIALS AND METHODS: Retrospective cohort study (2001-2014). POPULATION: patients with CD. Risk dose >50mSv. For calculating de cumulative effective dose and the CEED, all the ionizing test done were taken. For identifying predictive factors for receiving a CEDD >50mSv, an univariate and a multivariate logistic regression analyses were performed using a >50mSv dose as dependent variable. RESULTS: Of the 267 patients analyzed the 24.6% of them received a cumulative effective dose > 50mSv and the 15.2% a CEED>50mSv. In the multivariate analysis, the following variables were identified as independent predictors associated with a CEDD >50mSv: major surgery (OR= 2.1; IC95% [1.1-3.8]; p=.019) and severity (OR= 20.6; IC95% [4.5-94.8]; p<.01). CONCLUSIONS: Patients with CD are more at risk of receiving risk CEED, so it would be advisable to monitor the cumulative effective dose received to anticipate our intervention in order to avoid reaching that dose. The ultrasounds and abdominal resonance enterography are alternatives in these cases, although their accessibility is limited in some centers. PMID- 28988060 TI - Chandelier Cells Illuminate Inhibitory Control of Prefrontal-Amygdala Outputs. AB - Inhibitory interneurons comprise a diverse subpopulation of cells that are critical to circuit function. How distinct inhibitory microcircuits control long range projections remains poorly understood. A recent study by Lu and colleagues uncovered a unidirectional microcircuit of prefrontal chandelier cells that preferentially innervate and suppress long-range amygdala-projecting pyramidal cells. PMID- 28988061 TI - Nanolayered hybrid mediates synergistic co-delivery of ligand and ligation activator for inducing stem cell differentiation and tissue healing. AB - Cellular behaviors, such as differentiation, are regulated by complex ligation processes involving cell surface receptors, which can be activated by various divalent metal cations. The design of nanoparticle for co-delivery of ligand and ligation activator can offer a novel strategy to synergistically stimulate ligation processes in vivo. Here, we present a novel layered double hydroxide (LDH)-based nanohybrid (MgFe-Ado-LDH), composed of layered MgFe hydroxide nanocarriers sandwiching the adenosine cargo molecule, maintained through an electrostatic balance, to co-deliver the adenosine (Ado) ligand from the interlayer spacing and the Mg2+ ion (ligation activator) through the dissolution of the MgFe nanocarrier itself. Our findings demonstrate that the MgFe-Ado-LDH nanohybrid promoted osteogenic differentiation of stem cells through the synergistic activation of adenosine A2b receptor (A2bR) by the dual delivery of adenosine and Mg2+ ions, outperforming direct supplementation of adenosine alone. Furthermore, the injection of the MgFe-Ado-LDH nanohybrid and stem cells embedded within hydrogels promoted the healing of rat tibial bone defects through the rapid formation of fully integrated neo-bone tissue through the activation of A2bR. The newly formed bone tissue displayed the key features of native bone, including calcification, mature tissue morphology, and vascularization. This study demonstrates a novel and effective strategy of bifunctional nanocarrier mediated delivery of ligand (cargo molecule) and activation of its ligation to receptor by the nanocarrier itself for synergistically inducing stem cell differentiation and tissue healing in vivo, thus offering novel design of biomaterials for regenerative medicine. PMID- 28988062 TI - Single-walled carbon nanotube: One specific inhibitor of cancer stem cells in osteosarcoma upon downregulation of the TGFbeta1 signaling. AB - Cancer stem cells (CSCs) are believed to have a critical role in tumorigenesis, metastasis, therapeutic resistance or recurrence. Therefore, strategies designed to specifically target and eliminate CSCs have become one of the most promising and desirable ways for tumor treatment. Osteosarcoma stem cells (OSCs), the CSCs in osteosarcoma (OS), are critically associated with OS progression. Here, we show that single-walled carbon nanotubes (SWCNTs), including unmodified SWCNT (SWCNT-Raw) and SWCNT-COOH, have the ability to specifically inhibit the process of TGFbeta1-induced OS cells dedifferentiation, prevent the stem cell phenotypes acquisition in OS cells and reduce the OSC viability under conditions which mimic the OS microenvironment. Concurrently, SWCNT treatment significantly down regulates the expression of OSC markers in OS, and markedly reduces the tumor microvessel density and tumor growth. Furthermore, we found that SWCNT could suppress the TGFbeta1-induced activation of TGFbeta type I receptor and downstream signaling, which are key for the OSC formation and maintenance. Our results reveal an unexpected function of SWCNT in negative modulation of OSCs, and provide significant implications for the potential CSCs-targeted therapeutic applications of SWCNT. PMID- 28988063 TI - Spatial landscape model to characterize biological diversity using R statistical computing environment. AB - Due to urbanization and population growth, the degradation of natural forests and associated biodiversity are now widely recognized as a global environmental concern. Hence, there is an urgent need for rapid assessment and monitoring of biodiversity on priority using state-of-art tools and technologies. The main purpose of this research article is to develop and implement a new methodological approach to characterize biological diversity using spatial model developed during the study viz. Spatial Biodiversity Model (SBM). The developed model is scale, resolution and location independent solution for spatial biodiversity richness modelling. The platform-independent computation model is based on parallel computation. The biodiversity model based on open-source software has been implemented on R statistical computing platform. It provides information on high disturbance and high biological richness areas through different landscape indices and site specific information (e.g. forest fragmentation (FR), disturbance index (DI) etc.). The model has been developed based on the case study of Indian landscape; however it can be implemented in any part of the world. As a case study, SBM has been tested for Uttarakhand state in India. Inputs for landscape ecology are derived through multi-criteria decision making (MCDM) techniques in an interactive command line environment. MCDM with sensitivity analysis in spatial domain has been carried out to illustrate the model stability and robustness. Furthermore, spatial regression analysis has been made for the validation of the output. PMID- 28988064 TI - Positive appearance and functionality reflections can improve body satisfaction but do not protect against idealised media exposure. AB - We tested the effectiveness of a positive appearance or functionality reflective writing task on women's body satisfaction and whether these writing task reflections offered any protective advantage when exposed to idealised imagery. Young adult women (N=230; Mage=23years) wrote about positive elements of either their appearance or their body's functionality, and then were exposed to images of scenery, or thin and attractive models presented in posed or active form. Direction and amount of social comparison were also examined. Women reported immediate gains in both appearance and physical functionality satisfaction regardless of reflection type. However, neither reflection was protective against decreased satisfaction after exposure to idealised images. Greater upward comparison on either appearance or physical functionality domains was related to poorer outcomes. Our reflection task has potential to shift body focus but future research could examine multiple sessions and reflections on a broader range of self-relevant domains. PMID- 28988065 TI - Heterogeneity of Salmonella-host interactions in infected host tissues. AB - Infected host tissues have complex anatomy, diverse cell types, and dynamic inflammation. Traditional infection biology approaches largely ignore this complex host environment and its impact on pathogens, but recent single-cell technologies unravel extensively heterogeneous host-pathogen interactions in vivo. Salmonella are major model pathogens in this field due to the availability of excellent mouse disease models and facile molecular biology. The results show how Salmonella stochastically vary their virulence, exploit differential nutrient availability, experience and respond to widely varying stresses, and have disparate fates ranging from vigorous proliferation to eradication within the same host tissue. Specific Salmonella subsets drive disease progression, while others persist during antimicrobial chemotherapy. Further elucidation of the underlying mechanisms could provide a basis for improved infection control. PMID- 28988066 TI - Trauma patient discharge and care transition experiences: Identifying opportunities for quality improvement in trauma centres. AB - BACKGROUND: Challenges delivering quality care are especially salient during hospital discharge and care transitions. Severely injured patients discharged from a trauma centre will go either home, to rehabilitation or another acute care hospital with complex management needs. This purpose of this study was to explore the experiences of trauma patients and families treated in a regional academic trauma centre to better understand and improve their discharge and care transition experiences. METHODS: A qualitative study using inductive thematic analysis was conducted between March and October 2016. Telephone interviews were conducted with trauma patients and/or a family member after discharge from the trauma centre. Data collection and analysis were completed inductively and iteratively consistent with a qualitative approach. RESULTS: Twenty-four interviews included 19 patients and 7 family members. Participants' experiences drew attention to discharge and transfer processes that either (1) Fostered quality discharge or (2) Impeded quality discharge. Fostering quality discharge was ward staff preparation efforts; establishing effective care continuity; and, adequate emotional support. Impeding discharge quality was perceived pressure to leave the hospital; imposed transfer decisions; and, sub-optimal communication and coordination around discharge. Patient-provider communication was viewed to be driven by system, rather than patient need. Inter-facility information gaps raised concern about receiving facilities' ability to care for injured patients. CONCLUSIONS: The quality of trauma patient discharge and transition experiences is undermined by system- and ward-level processes that compete, rather than align, in producing high quality patient-centred discharge. Local improvement solutions focused on modifiable factors within the trauma centre include patient oriented discharge education and patient navigation; however, these approaches alone may be insufficient to enhance patient experiences. Trauma patients encounter complex barriers to quality discharge that likely require a comprehensive, multimodal intervention. PMID- 28988067 TI - The effect of resuscitation strategy on the longitudinal immuno-inflammatory response to blunt trauma. AB - INTRODUCTION: Resuscitation strategies following blunt trauma have been linked to immuno-inflammatory complications leading to systemic inflammatory syndrome (SIRS), sepsis and multiple organ failure (MOF). The effect of resuscitation strategy on longitudinal inflammation marker trajectories is, however, unknown. We hypothesized that the effect of resuscitation strategy extends beyond the trauma-related coagulopathy, perhaps affecting the longitudinal immuno inflammatory response to injury. METHODS: We analyzed data prospectively collected for the Inflammation and Host Response to Injury (Glue Grant) study. Blood sampling for inflammation marker analyses from blunt trauma patients was done on admission days 0, 1, 4, 7, 14, 21 and 28 where applicable. Total volume transfused of packed red blood cells (PRBC), fresh frozen plasma (FFP), platelets (PLT), and crystalloids during the initial 48h was extracted, along with an analysis for an array of cytokines by Enzyme Linked Immunosorbent Assay (ELISA) technique. A within patient concentration change (WPCC) was calculated to quantify longitudinal alterations in cytokine levels, while controlling for potential confounders. To account for the multiple comparisons performed, p values obtained from the multivariate regression model were post-hoc corrected by the false detection rate (FDR) q-value. RESULTS: No longitudinal trajectories of inflammatory markers were found to be associated with PRBC- or PLT transfusion. Three proinflammatory cytokines (Il-1beta, MIP-1beta, and TNFR2) were negatively associated with volume of FFP transfused (q=0.02, q<0.001 and q=0.007 respectively), and one proinflammatory cytokine (MIP-1beta) was positively associated with crystalloid infusion (q=0.005). CONCLUSIONS: Resuscitation strategy employed following blunt trauma has limited association to longitudinal inflammation marker trajectories, with a potential association between the strategy employed and IL-1beta, TNFR2, and MIP-1beta trajectories, respectively. PMID- 28988068 TI - Decapitation in reality and fine art: A review. AB - The aim of our study was to examine all types of decapitation from forensic literature, including our own case, and to analyze the presentation of beheading in fine art, popular literature, and music. To do this, over 200 scientific articles in regard to decapitation were analyzed, as well as more than 10,000 artworks, and several hundreds of literary works and music pieces. In addition, a macroscopic examination of a decapitated victim was performed. Finally, a multislice computerized tomography (MSCT) examination of the cervical spine in two live volunteers was undertaken to present the osteological relationships. The forensic and criminal investigation revealed that a female victim was murdered by her jealous husband by applying several strikes with an axe, which resulted in an incomplete decapitation. All the main neck structures were transected, including the cervical spine, except a smaller part of the skin and soft tissue in the nuchal region. The mentioned MSCT examination in both the neutral position and flexion showed that the mandible can also be injured in a higher cervical location of the severance line. Various types of beheading were mentioned, including a homicidal, suicidal, accidental, judicial, internal, pathophysiological, and foetal ones. The status of consciousness and emotions in individuals just before and after decapitation was discussed. Finally, it was found that decapitation was the subject of many artists, and some writers and musicians. In conclusion, we presented a rare case of a homicide beheading performed with an axe. In addition, forensic importance of decapitation was discussed, as well as its great medical, social, anthropological, and artistic significance. PMID- 28988069 TI - 2018 tallied facial soft tissue thicknesses for adults and sub-adults. AB - The tallied facial soft tissue thicknesses (or T-Tables) represent grand means of published facial soft tissue thickness sample means. These sample means have been drawn from across the full-breadth of the facial soft tissue thickness (FSTT) literature, including forensic science, anthropology and odontology. The report of new summary statistics for >1290 new sub-adults and >2200 new adults since the last T-Table calculation, in 2008 for sub-adults and 2013 for adults respectively, makes their update timely. The maximum sample sizes at any landmark now stand at 3023 for individuals aged 0-11 years old (g-g'); 3145 for individuals aged 12-17 years old (n-se'); and 10,333 for adults (n-se'). Following the recalculation of grand weighted means and comparison to the original 2008 data, some shifts in the T-Table statistics are evident at specific landmarks, namely: 2-2.5mm increases at gonion (go-go') and mid-mandibular border (mmb-mmb') for adults; 3.5mm decrease at gonion (go-go') for 12-17year olds; and 2.0mm decrease at menton (me-me') for 0-11year olds. Differences at all other landmarks (91-100% depending on the dataset) were minimal being <1.0mm. Performance tests of the new grand means as point estimators (using individuals with known FSTT size from the C-Table), show the 2018 T-Table statistics to produce marginally less error than the 2013 means: 2018 standard error of the estimate=3.7mm in contrast to 2013 standard error of the estimate=3.9mm. The long run nature of the T-Table statistics (i.e., big data) and quantified performance test accuracies on known subjects, earmark the 2018 T-Table as the premier FSTT standard for craniofacial identification casework. In the distant future, this is likely to change as the C-Table raw data repository grows, allowing shorths and shormaxes to be calculated for large samples. Given current raw data repository sample sizes of 0-1574 for T-Table landmarks (notably lower for younger individuals), there is some way to go before enhanced central tendency estimators can entirely replace untrimmed arithmetic means. PMID- 28988070 TI - Prokaryotic communities and potential pathogens in sewage sludge: Response to wastewaster origin, loading rate and treatment technology. AB - Sewage sludge features high nitrogen and phosphorous contents encouraging its use as a biosolid in agriculture, but it bears potential chemical and microbiological risks. To tease apart the relative contribution of main factors determining the sludge chemical and microbial features, we analysed 28 treatment plants differing in the wastewater origin (municipal residues, agro-food or chemical industries), organic loading rate and treatment technology (extended aeration, activated sludge or activated sludge followed by anaerobic digestion). We found that the treatment technology and the organic loading rate are main determinants of the sludge chemical properties, including its organic load, nutrient and metal contents, and override the effect of the wastewater origin. Sludge bacterial and archaeal community structure and diversity, characterized through massive sequencing of the 16S rRNA gene, were also mostly determined by the treatment technology partly through shifts in the sludge nutrient load. The same factor conditioned the relative abundance of sequenced bacteria most closely related to potential pathogens, but not that of cultivable Escherichia coli or Salmonella spp. We did not find an effect of the geographic location of the plant on any of the variables at the regional scale of our study. Operational parameters appear as major determinants of the sludge chemical and microbial properties, irrespective of the source of wastewaters, thus leaving a broad management window for improving the agronomic value of sewage sludge. PMID- 28988071 TI - Effects of particulate matter exposure during pregnancy on birth weight: A retrospective cohort study in Suzhou, China. AB - BACKGROUND: Recent studies have identified that exposure to particulate matter during pregnancy could result in adverse birth outcomes, but the effects of exposure at trimester-specific intervals are inconsistent. OBJECTIVE: Our primary goal was to investigate whether particulate matter exposure during pregnancy could affect birth weight and gestational age of neonates. METHODS: A retrospective cohort study was conducted to examine the relationship between maternal particulate matter exposure and neonatal birth weight. We collected 14,455 births records linked to hospital admission records (delivery and antenatal) from January 2013 to December 2015 in Suzhou Municipal Hospital. Air monitoring data in the same timeframe were also collected from Suzhou Environmental Protection Agency. The risk of low birth weight due to the exposure to PM2.5 (with median aerodynamic diameter<=2.5MUm) and PM10 (with median aerodynamic diameter<=10MUm) at each trimester and throughout the entire pregnancy were assessed. Linear regression models were applied and potential confounding factors were adjusted for data analysis. Gestational age, which was another important birth outcome, and its association with maternal particulate matter exposure were also studied. RESULTS: The final analysis included 10,915 singleton live births. Using multiple linear regression models, we found that gestational exposure to PM2.5 and PM10 at 10MUg/m3 increments in the second trimester led to decreases in birth weight of 4.94g (95% confidence interval: 9.828, -0.046) and 5.65g (95% confidence interval: -10.110, -1.188), respectively. However, gestational age was not significantly associated with maternal particulate matter exposure in term neonates. CONCLUSION: These findings indicate that pregnant women might be more susceptible to particulate matter during the second trimester which may lead to decreased neonatal birth weight. PMID- 28988072 TI - TiO2 nanoparticles in the marine environment: Impact on the toxicity of phenanthrene and Cd2+ to marine zooplankton Artemia salina. AB - The impact of manufactured nanoparticles on the toxicity of co-existing pollutants in aquatic environments has raised increasing concerns. However, the toxicity of polycyclic aromatic hydrocarbons or metal ions in the presence of titanium dioxide nanoparticles (nTiO2) to marine zooplankton has been rarely reported. In the present study, the impacts of nTiO2 on the toxicity of phenanthrene (Phe) and cadium (Cd2+) to Artemia salina, a model marine zooplankton, were investigated. Although nTiO2 alone exerted a limited toxicity to A. salina within 48h of exposure, nTiO2 strongly altered the toxicity of Phe and Cd2+ to A. salina. Compared with the individual toxicities of pollutants to A. salina, the toxicities of Phe and Cd2+ increased by 2.0% and 12.2%, respectively, in the presence of 5mg/L nTiO2, but decreased by 24.5% and 57.1%, respectively, in the presence of 400mg/L nTiO2. These concentration-dependent impacts of nTiO2 on the toxicity of Phe or Cd2+ might be attributed to the concurrent functions of several interrelated factors including the adsorption of pollutants on nTiO2, the nTiO2-faciliated bioaccumulation of pollutants, the limited gut volume in organisms, and the aggregation and sedimentation behaviors of nTiO2. These results presented in the study could help understand the effects of manufactured nanomaterials in marine environments. PMID- 28988073 TI - Groundwater footprint methodology as policy tool for balancing water needs (agriculture & tourism) in water scarce islands - The case of Crete, Greece. AB - In many Mediterranean islands with limited surface water resources, the growth of agricultural and touristic sectors, which are the main water consumers, highly depends on the sustainable water resources management. This work highlights the crucial role of groundwater footprint (GF) as a tool for the sustainable management of water resources, especially in water scarce islands. The groundwater footprint represents the water budget between inflows and outflows in an aquifer system and is used as an index of the effect of groundwater use in natural resources and environmental flows. The case study presented in this paper is the island of Crete, which consists of 11 main aquifer systems. The data used for estimating the groundwater footprint in each system were groundwater recharges, abstractions through 412 wells, environmental flows (discharges) from 76 springs and 19 streams present in the area of study. The proposed methodology takes into consideration not only the water quantity but also the water quality of the aquifer systems and can be used as an integrated decision making tool for the sustainable management of groundwater resources. This methodology can be applied in any groundwater system. The results serve as a tool for assessing the potential of sustainable use and the optimal distribution of water needs under the current and future climatic conditions, considering both quantitative and qualitative factors. Adaptation measures and water policies that will effectively promote sustainable development are also proposed for the management of the aquifer systems that exhibit a large groundwater footprint. PMID- 28988074 TI - Asset management to support urban land and subsurface management. AB - Pressure on urban areas increases by demographic and climate change. To enable healthy, adaptive and liveable urban areas different strategies are needed. One of the strategies is to make better use of subsurface space and its functions. Asset management of the Subsurface (AMS) contributes to this. Asset management provides transparency of trade-offs between performance, cost and risks throughout the entire lifecycle of these assets. AMS is based on traditional asset management methods, but it does not only take man-made assets in the subsurface into account. AMS also considers the natural functions that the subsurface, including groundwater, has to offer (ecosystem services). A Dutch community of practice consisting of national and municipal authorities, a consultancy-engineering and a research institute are developing AMS in practice in order to 1) enhance the urban underground space planning (using its benefits, avoiding problems) and 2) use, manage and maintain the (urban) subsurface and its functions. The method is currently still under development. PMID- 28988075 TI - Feasibility of a portable X-ray fluorescence device for bone lead measurements of condor bones. AB - Lead based ammunition is a primary source of lead exposure, especially for scavenging wildlife. Lead poisoning remains the leading cause of diagnosed death for the critically endangered California condors, which are annually monitored via blood tests for lead exposure. The results of these tests are helpful in determining recent exposure in condors and in defining the potential for exposure to other species including humans. Since condors are victim to acute and chronic lead exposure, being able to measure both would lend valuable information on the rates of exposure and accumulation through time. A commercial portable X-ray fluorescence (XRF) device has been optimized to measure bone lead in vivo in humans, but this device could also be valuable for field measurements of bone lead in avian species. In this study, we performed measurements of bone Pb in excised, bare condor bones using inductively coupled plasma mass spectrometry (ICP-MS), a cadmium 109 (Cd-109) K-shell X-ray fluorescence (KXRF) system, and a portable XRF system. Both KXRF and portable XRF bone Pb measurement techniques demonstrated good correlations with ICP-MS results (r=0.93 and r=0.92 respectively), even with increasing skin thickness (r=0.86 between ICP-MS and portable XRF at 1.54mm of soft tissue). In conclusion, our results suggest that a portable XRF could be a useful option for measurement of bone Pb in avian species in the field. PMID- 28988076 TI - Carbon and energy footprint of the hydrate-based biogas upgrading process integrated with CO2 valorization. AB - The present paper aims at assessing the carbon and energy footprint of an energy process, in which the energy excess from intermittent renewable sources is used to produce hydrogen which reacts with the CO2 previously separated from an innovative biogas upgrading process. The process integrates a hydrate-based biogas upgrading section and a CO2 methanation section, to produce biomethane from the biogas enrichment and synthetic methane from the CO2 methanation. Clathrate hydrates are crystalline compounds, formed by gas enclathrated in cages of water molecules and are applied to the selective separation of CO2 from biogas mixtures. Data from the experimental setup were analyzed in order to evaluate the green-house gas emissions (carbon footprint CF) and the primary energy consumption (energy footprint EF) associated to the two sections of the process. The biosynthetic methane production during a single-stage process was 0.962Nm3, obtained mixing 0.830Nm3 of methane-enriched biogas and 0.132Nm3 of synthetic methane. The final volume composition was: 73.82% CH4, 19.47% CO2, 0.67% H2, 1.98% O2, 4.06% N2 and the energy content was 28.0MJ/Nm3. The functional unit is the unitary amount of produced biosynthetic methane in Nm3. Carbon and energy footprints are 0.7081kgCO2eq/Nm3 and 28.55MJ/Nm3, respectively, when the electric energy required by the process is provided by photovoltaic panels. In this scenario, the overall energy efficiency is about 0.82, higher than the worldwide average energy efficiency for fossil methane, which is 0.75. PMID- 28988077 TI - Levels, congener profiles, and dietary intake assessment of polychlorinated dibenzo-p-dioxins/dibenzofurans and dioxin-like polychlorinated biphenyls in beef, freshwater fish, and pork marketed in Guangdong Province, China. AB - Persistent organic pollutants such as polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin-like polychlorinated biphenyls (DL-PCBs) consisting of non-ortho and mono-ortho PCBs are suggested to be very hazardous and have adverse effects on human health. However, their levels and congener profiles in retail foods marketed in Guangdong Province of China have not been elucidated thus far. Thus, in this study, 226 individual samples of beef, freshwater fish, and pork marketed across four regions of Guangdong Province were randomly collected during 2013-2015 to determine their levels of PCDD/Fs and DL-PCBs. The results showed that the total toxic equivalency quantities (TEQs) of most samples were below the maximum limits except for the 26 samples collected from the vicinities of pollution areas. The median total TEQs of these three categories were 0.174, 0.488, and 0.113pgTEQ/g fw, respectively, which indicated that the contamination status of the studied foods was not serious. For congener profiles, significantly different patterns were observed in three food groups, but with the same major TEQ contributors being 2,3,4,7,8-PeCDF in beef, freshwater fish, and pork. Regional differences of congener profiles in each food group were also found in this study, which might be attributed to the regionally different distributions of PCDD/Fs and DL-PCBs in environment media. The dietary exposures of four population subgroups (girls, boys, male adults, and female adults) to PCDD/Fs and DL-PCBs via three food groups were estimated to assessed the potential risks. They were all lower than the provisional tolerable monthly intake (PTMI, 70pgTEQ/kgbw/month) established by Joint FAO/WHO Expert Committee on Food Additive. In these food categories, the exposure to PCDD/Fs and DL-PCBs via freshwater fish was the highest one, which accounted for about 20% of PTMI, indicating that it was the major route to expose dioxin compounds. PMID- 28988078 TI - Synthesis composite hydrogels from inorganic-organic hybrids based on leftover rice for environment-friendly controlled-release urea fertilizers. AB - Nearly 1.3 billion tons of food are discarded annually in the production process. In this study, a novel slow-release nitrogen fertilizer with water absorbency was developed using leftover rice and crosslinking methods. Urea was incorporated as the nitrogen source in a leftover rice-g-poly(acrylic acid)/montmorillonite (LR-g PAA/MMT) network, and then the leftover rice-g-poly(acrylic acid)/montmorillonite/Urea (LR-g-PAA/MMT/Urea) retained in the soil, and used as the loss control agent for water and nutrients. Variables including concentrations of acrylic acid, montmorillonite, N,N'-methylenebis acrylamide (MBA), and potassium persulfate (KPS) were investigated. Samples were with a water absorbency of 102.6g/g in distilled water and 25.1g/g in 1.0wt% NaCl solution under optimized conditions. Swelling measurements and water-retention indicated that higher-covalent cations would aggregate the hydrogels and decrease swelling. Investigating leaching behavior showed that these samples have the potential to carry the necessary nitrogen (N). The results demonstrated that the LR-g-PAA/MMT/Urea had a low leaching losses of N (19.7%) compared with pure urea (52.3%). Therefore, the developed fertilizer may be widely applicable in agriculture and horticulture, and could provide a new platform for reusing leftover rice. PMID- 28988079 TI - Preparation and characterization of slow-release fertilizer encapsulated by biochar-based waterborne copolymers. AB - To enhance the effectiveness of polyvinyl alcohol (PVA) coated fertilizers, a novel slow-release fertilizer was developed using biochar and waterborne copolymer of PVA and polyvinylpyrrolidone (PVP) as coating materials. The effects of botanical origins and doses of biochar as well as copolymer concentrations on biochar-copolymer structures and properties were investigated. Our results indicated that the water absorbency of blend films differing in biochar origins showed different responses to these three factors. Generally, biochar decreased water absorbency of copolymer with an increased degradability, and contributed to improving the slow-release property of coated urea. In particular, rice biochar based copolymer (S5 film) had less hydrophilic OH bonds and encapsulated urea granules more compactly and densely. The urea particles coated with rice biochar based copolymer (S5 film) exhibited an excellent release behavior of 65.28% nutrient leaching on the 22th day. Therefore, this work has demonstrated the potential of biochar-based copolymer from different botanical biochar for improving the effectiveness of fertilizers. PMID- 28988080 TI - Flood susceptibility mapping using novel ensembles of adaptive neuro fuzzy inference system and metaheuristic algorithms. AB - Flood is one of the most destructive natural disasters which cause great financial and life losses per year. Therefore, producing susceptibility maps for flood management are necessary in order to reduce its harmful effects. The aim of the present study is to map flood hazard over the Jahrom Township in Fars Province using a combination of adaptive neuro-fuzzy inference systems (ANFIS) with different metaheuristics algorithms such as ant colony optimization (ACO), genetic algorithm (GA), and particle swarm optimization (PSO) and comparing their accuracy. A total number of 53 flood locations areas were identified, 35 locations of which were randomly selected in order to model flood susceptibility and the remaining 16 locations were used to validate the models. Learning vector quantization (LVQ), as one of the supervised neural network methods, was employed in order to estimate factors' importance. Nine flood conditioning factors namely: slope degree, plan curvature, altitude, topographic wetness index (TWI), stream power index (SPI), distance from river, land use/land cover, rainfall, and lithology were selected and the corresponding maps were prepared in ArcGIS. The frequency ratio (FR) model was used to assign weights to each class within particular controlling factor, then the weights was transferred into MATLAB software for further analyses and to combine with metaheuristic models. The ANFIS PSO was found to be the most practical model in term of producing the highly focused flood susceptibility map with lesser spatial distribution related to highly susceptible classes. The chi-square result attests the same, where the ANFIS-PSO had the highest spatial differentiation within flood susceptibility classes over the study area. The area under the curve (AUC) obtained from ROC curve indicated the accuracy of 91.4%, 91.8%, 92.6% and 94.5% for the respective models of FR, ANFIS-ACO, ANFIS-GA, and ANFIS-PSO ensembles. So, the ensemble of ANFIS-PSO was introduced as the premier model in the study area. Furthermore, LVQ results revealed that slope degree, rainfall, and altitude were the most effective factors. As regards the premier model, a total area of 44.74% was recognized as highly susceptible to flooding. The results of this study can be used as a platform for better land use planning in order to manage the highly susceptible zones to flooding and reduce the anticipated losses. PMID- 28988081 TI - Measurements of nonvolatile size distribution and its link to traffic soot in urban Shanghai. AB - Measurements of particle size distribution and size-resolved particle volatility were conducted using a volatility tandem differential mobility analyzers (V-TDMA) in the urban area of Shanghai during wintertime in January 2014. The nonvolatile mode particles with VSF exceeding 0.85 were always externally mixed with more volatile mode particles. The average VSF ranged from 0.58 to 0.65 for 100-400nm particles, increasing with the increase of particle size. On average, the nonvolatile mode contributed 15-20% of number fraction for 50-400nm particles. Due to their hydrophobic nature, the nonvolatile particles were not easily removed by wet deposition. The concentrations of the nonvolatile mode particles and NOx were well correlated, indicating that the nonvolatile mode particles were mostly attributed to be fresh traffic soot. The diurnal variations in ensemble VSF and number fraction of nonvolatile mode particles exhibited two peaks in clean days, corresponding to morning and evening rush hours. The VSF distributions of 50nm particles were similar during a transition between haze to clean periods whereas in the accumulation mode range, the number fraction of more volatile mode and the amount of volatile materials in the more-volatile mode particles during haze periods are considerably larger than those in clean periods, indicating different contribution from transported sources. PMID- 28988082 TI - Degradation of nonylphenol polyethoxylates by functionalized Fe3O4 nanoparticle immobilized Sphingomonas sp. Y2. AB - : In this study, the efficiency of the nonylphenol polyethoxylates (NPEOs) degrading bacterium Sphingomonas sp. strain Y2 was evaluated, which was immobilized by a novel system composed of polydopamine (PD)-coated Fe3O4 iron nanoparticles (IONPs). The PD-IONPs, with a distinct core-shell structure, relatively uniform size, and high saturation magnetization, were prepared for Y2 immobilization. The performance of Y2 was unaffected by this novel immobilization method, exhibiting 79.5% and 99.9% of NPEOs (500ppm) degradation efficiency at day 1 and 2, respectively. Furthermore, separation and recycling were more readily achieved for immobilized cells as compared to free cells. Immobilized cells retained over 70% of the original degradation activity after 6cycles of utilization. These results suggest that Y2-PD-IONPs can be potentially used for NPEOs-contaminated wastewater bioremediation. CAPSULE: Immobilization of Sphingomonas sp. Y2 by functionalized PD-IONPs with easy separation, recycling utilization and high efficiency. PMID- 28988083 TI - High-resolution sedimentary records of some organochlorine pesticides in Yamzho Yumco Lake of the Tibetan Plateau: Concentration and composition. AB - Sediment cores from lakes have been used to reconstruct the historic deposition of persistent organic pollutants (POPs), especially in remote alpine areas. To reconstruct the deposition history of organochlorine pesticides (OCPs) in the Tibetan Plateau (TP), two sediment cores from Yamzho Yumco Lake were drilled and dated with high-resolution, from which 23 OCPs were analyzed in greater detail. Regarding several legacy compounds, concentration peaks in the cores were observed in the 1970s, corresponding to the heavy usage of these compounds around the world. In addition, another peak was found at the end of the 1990s, which was explained as the addition of OCPs released from melting glaciers or the cryosphere due to global warming. Furthermore, it was found that the transformation or degradation of OCPs after deposition in the lake was limited by comparing the values of isomeric ratios at different times, such as (DDD+DDE)/?DDTs, o,p'-DDT/p,p'-DDT and beta-HCH/?HCHs. Such results ensure that the detected OCPs in the lake sediments really reflect their characteristics at the time of deposition. On the other hand, weak environmental self-purification of the OCPs made them last longer in the TP than in other regions. Reasonably, the fragile ecological environment of the TP would be threatened not only by legacy POPs that remain in the sediments and soils but also by POPs released from melting glaciers or the cryosphere in the next few decades under the influence of global warming. Our research provides an insight into the influence of global warming and glacial melting on the environment of the TP, and further work to gain a better understanding of the environmental processes of POPs in the TP is ongoing. PMID- 28988084 TI - Fluorescent sensor based models for the detection of environmentally-related toxic heavy metals. AB - The quest for industrial and biotechnological revolution has been contributed in increasing environmental contamination issues, worldwide. The controlled or uncontrolled release of hazardous pollutants from various industrial sectors is one of the key problems facing humanity. Among them, adverse influences of lead, cadmium, and mercury on human health are well known to cause many disorders like reproductive, neurological, endocrine system, and cardiovascular, etc. Besides their presence at lower concentrations, most of these toxic heavy metals are posing noteworthy toxicological concerns. In this context, notable efforts from various regulatory authorities, the increase in the concentration of these toxic heavy metals in the environment is of serious concern, so real-time monitoring is urgently required. This necessitates the exploration for novel and efficient probes for recognition of these toxic agents. Among various methodologies adopted for tailoring such probes, generally the methodologies, in which changes associated with spectral properties, are preferred for the deceptive ease in the recognition process. Accordingly, a promising modality has emerged in the form of radiometric and colorimetric monitoring of these toxic agents. Herein, we review fluorescent sensor based models and their potentialities to address the detection fate of hazardous pollutants for a cleaner environment. Second, recent advances regarding small molecule and rhodamine-based fluorescent sensors, radiometric and colorimetric probes are discussed. The information is also given on the photoinduced electron transfer (PET) mechanism, chelation enhancement fluorescence (CHEF) effect and spirocyclic ring opening mechanism. PMID- 28988085 TI - Aging effects on chemical transformation and metal(loid) removal by entrapped nanoscale zero-valent iron for hydraulic fracturing wastewater treatment. AB - In this study, alginate and polyvinyl alcohol (PVA)-alginate entrapped nanoscale zero-valent iron (nZVI) was tested for structural evolution, chemical transformation, and metals/metalloids removal (Cu(II), Cr(VI), Zn(II), and As(V)) after 1-2month passivation in model saline wastewaters from hydraulic fracturing. X-ray diffraction analysis confirmed successful prevention of Fe0 corrosion by polymeric entrapment. Increasing ionic strength (I) from 0 to 4.10M (deionized water to Day-90 fracturing wastewater (FWW)) with prolonged aging time induced chemical instability of alginate due to dissociation of carboxyl groups and competition for hydrogen bonding with nZVI, which caused high Na (7.17%) and total organic carbon (24.6%) dissolution from PVA-alginate entrapped nZVI after 2 month immersion in Day-90 FWW. Compared to freshly-made beads, 2-month aging of PVA-alginate entrapped nZVI in Day-90 FWW promoted Cu(II) and Cr(VI) uptake in terms of the highest removal efficiency (84.2% and 70.8%), pseudo-second-order surface area-normalized rate coefficient ksa (2.09*10-1Lm-2h-1 and 1.84*10-1Lm-2h 1), and Fe dissolution after 8-h reaction (13.9% and 8.45%). However, the same conditions inhibited Zn(II) and As(V) sequestration in terms of the lowest removal efficiency (31.2% and 39.8%) by PVA-alginate nZVI and ksa (4.74*10-2Lm-2h 1 and 6.15*10-2Lm-2h-1) by alginate nZVI. The X-ray spectroscopic analysis and chemical speciation modelling demonstrated that the difference in metals/metalloids removal by entrapped nZVI after aging was attributed to distinctive removal mechanisms: (i) enhanced Cu(II) and Cr(VI) removal by nZVI reduction with accelerated electron transfer after pronounced dissolution of non conductive polymeric immobilization matrix; (ii) suppressed Zn(II) and As(V) removal by nZVI adsorption due to restrained mass transfer after blockage of surface-active micropores. Entrapped nZVI was chemically fragile and should be properly stored and regularly replaced for good performance. PMID- 28988086 TI - Proteome and phospholipid alteration reveal metabolic network of Bacillus thuringiensis under triclosan stress. AB - Triclosan is a common antibacterial agent widely applied in various household and personal care products. The molecule, cell, organ and organism-level understanding of its toxicity pose to some target organisms has been investigated, whereas, the alteration of a single metabolic reaction, gene or protein cannot reflect the impact of triclosan on metabolic network. To clarify the interaction between triclosan stress and metabolism at network and system levels, phospholipid synthesis, and cellular proteome and metabolism of Bacillus thuringiensis under 1MUM of triclosan stress were investigated through omics approaches. The results showed that C14:0, C16:1omega7, C16:0 and C18:2omega6 were significantly up-produced, and 19 proteins were differentially expressed. Whereas, energy supply, protein repair and the synthesis of DNA, RNA and protein were down-regulated. PyrH and Eno could be biomarkers to reflect triclosan stress. At network level, the target proteins ACOX1, AHR, CAR, CYP1A, CYP1B1, DNMT1, ENO, HSP60, HSP70, SLC5A5, TPO and UGT expressed in different species shared high sequence homology with the same function proteins found in Homo sapiens not only validated their role as biomarkers but also implied the potential impact of triclosan on the metabolic pathways and network of humans. These findings provided novel insights into the metabolic influence of triclosan at network levels, and developed an omics approach to evaluate the safety of target compound. PMID- 28988087 TI - Irrigation and weed control alter soil microbiology and nutrient availability in North Carolina Sandhill peach orchards. AB - Orchard management practices such as weed control and irrigation are primarily aimed at maximizing fruit yields and economic profits. However, the impact of these practices on soil fertility and soil microbiology is often overlooked. We conducted a two-factor experimental manipulation of weed control by herbicide and trickle irrigation in a nutrient-poor peach (Prunus persica L. cv. Contender) orchard near Jackson Springs, North Carolina. After three and eight years of treatments, an array of soil fertility parameters were examined, including soil pH, soil N, P and cation nutrients, microbial biomass and respiration, N mineralization, and presence of arbuscular mycorrhizal fungi (AMF). Three general trends emerged: 1) irrigation significantly increased soil microbial biomass and activity, 2) infection rate of mycorrhizal fungi within roots were significantly higher under irrigation than non-irrigation treatments, but no significant difference in the AMF community composition was detected among treatments, 3) weed control through herbicides reduced soil organic matter, microbial biomass and activity, and mineral nutrients, but had no significant impacts on root mycorrhizal infection and AMF communities. Weed-control treatments directly decreased availability of soil nutrients in year 8, especially soil extractable inorganic N. Weed control also appears to have altered the soil nutrients via changes in soil microbes and altered net N mineralization via changes in soil microbial biomass and activity. These results indicate that long-term weed control using herbicides reduces soil fertility through reducing organic C inputs, nutrient retention and soil microbes. Together, these findings highlight the need for alternative practices such as winter legume cover cropping that maintain and/or enhance organic inputs to sustain the soil fertility. PMID- 28988088 TI - Low temperature geothermal systems in carbonate-evaporitic rocks: Mineral equilibria assumptions and geothermometrical calculations. Insights from the Arnedillo thermal waters (Spain). AB - Geothermometrical calculations in low-medium temperature geothermal systems hosted in carbonate-evaporitic rocks are complicated because 1) some of the classical chemical geothermometers are, usually, inadequate (since they were developed for higher temperature systems with different mineral-water equilibria at depth) and 2) the chemical geothermometers calibrated for these systems (based on the Ca and Mg or SO4 and F contents) are not free of problems either. The case study of the Arnedillo thermal system, a carbonate-evaporitic system of low temperature, will be used to deal with these problems through the combination of several geothermometrical techniques (chemical and isotopic geothermometers and geochemical modelling). The reservoir temperature of the Arnedillo geothermal system has been established to be in the range of 87+/-13 degrees C being the waters in equilibrium with respect to calcite, dolomite, anhydrite, quartz, albite, K-feldspar and other aluminosilicates. Anhydrite and quartz equilibria are highly reliable to stablish the reservoir temperature. Additionally, the anhydrite equilibrium explains the coherent results obtained with the delta18O anhydrite - water geothermometer. The equilibrium with respect to feldspars and other aluminosilicates is unusual in carbonate-evaporitic systems and it is probably related to the presence of detrital material in the aquifer. The identification of the expected equilibria with calcite and dolomite presents an interesting problem associated to dolomite. Variable order degrees of dolomite can be found in natural systems and this fact affects the associated equilibrium temperature in the geothermometrical modelling and also the results from the Ca Mg geothermometer. To avoid this uncertainty, the order degree of the dolomite present in the Arnedillo reservoir has been determined and the results indicate 18.4% of ordered dolomite and 81.6% of disordered dolomite. Overall, the results suggest that this multi-technique approach is very useful to solve some of the problems associated to the study of carbonate-evaporitic geothermal systems. PMID- 28988089 TI - The location- and scale- specific correlation between temperature and soil carbon sequestration across the globe. AB - Much research has been conducted to understand the spatial distribution of soil carbon stock and its temporal dynamics. However, an agreement has not been reached on whether increasing global temperature has a positive or negative feedback on soil carbon stocks. By analysing global maps of soil organic carbon (SOC) using a spherical wavelet analysis, it was found that the correlation between SOC and soil temperature at the regional scale was negative between 52 degrees N and 40 degrees S parallels and positive beyond this region. This was consistent with a few previous studies and it was assumed that the effect was most likely due to the temperature-dependent SOC formation (photosynthesis) and decomposition (microbial activities and substrate decomposability) processes. The results also suggested that the large SOC stocks distributed in the low temperature areas might increase under global warming while the small SOC stocks found in the high-temperature areas might decrease accordingly. Although it remains unknown whether the potential increasing soil carbon stocks in the low temperature areas can offset the loss of carbon stocks in the high-temperature areas, the location- and scale- specific correlations between SOC and temperature should be taken into account for modeling SOC dynamics and SOC sequestration management. PMID- 28988090 TI - Magnetite nanoparticles supported on organically modified montmorillonite for adsorptive removal of iodide from aqueous solution: Optimization using response surface methodology. AB - Magnetite nanoparticles supported on organically modified montmorillonite (MNP OMMTs) were successfully synthesized by a facile coprecipitation method. The surface of natural clay was modified using a cationic surfactant, hexadecyltrimethylammonium. The synthesized MNP-OMMTs were used as an adsorbent to remove iodide from aqueous solutions. The maximum adsorption capacity of the adsorbent was 322.42mg/g, which is much higher than other previously reported adsorbents for removing iodide in aqueous solution. The experimental data were well fitted to a pseudo-second-order kinetic model, and the adsorption behavior followed the Langmuir isotherm. A thermodynamic study indicated that iodide adsorption was spontaneous and endothermic. The individual and combined effects of key process parameters (pH, temperature, and initial iodide concentration) were studied using a response surface methodology. The maximum iodide removal efficiency of 93.81% was obtained under the optimal conditions of pH3.9, a temperature of 41.3 degrees C, and an initial iodide concentration of 113.8mg/L. PMID- 28988091 TI - Short-term effects of fine particulate matter on acute myocardial infraction mortality and years of life lost: A time series study in Hong Kong. AB - Previous studies have applied years of life lost (YLL) as a complementary indicator to assess the short-term effect of the air pollution on the health burden from all-cause mortality, but sparsely focused on individual diseases such as acute myocardial infraction (AMI). In this study, we aimed to conduct a time series analysis to evaluate short-term effects of fine particulate matter (PM2.5) on mortality and YLL from AMI in Hong Kong from 2011 to 2015, and explore the potential effect modifiers including sex and age by subgroup analysis. We applied generalized additive Poisson and Gaussian regression model for daily death count and YLL, respectively. We found that 10MUg/m3 increment in concentration of PM2.5 lasting for two days (lag01) was associated with a 2.35% (95% CI 0.38% to 4.36%) increase in daily mortality count and a 1.69 (95% CI 0.01 to 3.37) years increase in YLL from AMI. The association between PM2.5 and AMI mortality count was stronger among women and older people than men and young people, respectively. We concluded that acute exposure to PM2.5 may increase the risk of mortality and YLL from AMI in Hong Kong and this effect can be modified by age and gender. These findings add to the evidence base for public health policy formulation and resource allocation. PMID- 28988092 TI - A new methodology for estimating rainfall aggressiveness risk based on daily rainfall records for multi-decennial periods. AB - The temporal irregularity of rainfall, characteristic of a Mediterranean climate, corresponds to the irregularity of the environmental effects on soil. We used aggressiveness as an indicator to quantify the potential environmental impact of rainfall. However, quantifying rainfall aggressiveness is conditioned by the lack of sub-hourly frequency records on which intensity models are based. On the other hand, volume models are characterized by a lack of precision in the treatment of heavy rainfall events because they are based on monthly series. Therefore, in this study, we propose a new methodology for estimating rainfall aggressiveness risk. A new synthesis parameter based on reformulation using daily data of the Modified Fournier and Oliver's Precipitation Concentration indices is defined. The weighting of both indices for calculating the aggressiveness risk is established by multiple regression with respect to the local erosion R factor estimated in the last decades. We concluded that the proposed methodology overcomes the previously mentioned limitations of the traditional intensity and volume models and provides accurate information; therefore, it is appropriate for determining potential rainfall impact over long time periods. Specifically, we applied this methodology to the daily rainfall time series from the San Fernando Observatory (1870-2010) in southwest Europe. An interannual aggressiveness risk series was generated, which allowed analysis of its evolution and determination of the temporal variability. The results imply that environmental management can use data from long-term historical series as a reference for decision making. PMID- 28988093 TI - A methodological framework for coastal development assessment: A case study of Fujian Province, China. AB - Decision-makers often have to make trade-offs between economic growth and environmental conservation when developing and managing coastal environments. Coastal development and management need to be subject to rigorous assessments to determine if they are sustainable over time. We propose a methodological framework - the Coastal Development Index (CDI) for the assessment of the changes in sustainability of coastal development over time. CDI is a modified version of the Ocean Health Index (OHI) but with two new indicators - ecological and environmental indicators (EEI), and social and economic indicators (SEI), both of which comprise three sub-indicators (coastal protection, clean waters and species protection for EEI, and food provision, coastal livelihoods and economies and tourism and recreation for SEI). The six sub-indicators represent key aspects of coastal development and the level of exploitation of natural resources that have previously been missing in other conceptual frameworks. We demonstrate the value of CDI with a detailed case study of Fujian Province in China, 2000-2013. The scores of CDI decreased from 1.01 in 2000 to 0.42 in 2013 suggesting that the Fujian coastal zone has experienced unsustainable development in that time. Meanwhile, the scores of EEI decreased from 22.1 to 20.4 while the scores of SEI increased from 21.9 to 48.1 suggesting that environmental values have been eroded by economic growth. Analysis of the scores of sub-indicators reveals a need to integrate economic growth and social development with environmental conservation on Fujian coastal management. Our case study highlights the potential value of the CDI for improving the ecological sustainability of coastal zone management and development practices. PMID- 28988094 TI - Integrate carbon dynamic models in analyzing carbon sequestration impact of forest biomass harvest. AB - Biomass is an attractive natural energy resource for mitigating climate change. However, the loss of carbon sequestration as an ecosystem service due to biomass harvest has not been considered in previous studies. To assess the impact of biomass harvest on carbon sequestration, carbon dynamics in the forests and the atmosphere were integrated. The impact of forest biomass harvests on carbon sequestration was assessed based on the difference between carbon sequestration after harvest and carbon sequestration without harvest. A Chapman-Richards function and the forest vegetation simulator (FVS) were used to simulate the growth of a forest stand. The carbon dynamics in the atmosphere were simulated by the Bern2.5CC carbon cycle model. Characterization factors of the impact were calculated in three time horizons: 20-, 100- and 500-year. According to the simulations, postponement of harvest and low harvest intensity could prolong the compensation period. The annual impact on carbon sequestration was mostly negative over a short time and became positive in the end of compensation period. The highest characteristic factors of the impact on carbon sequestration were found in rotation length of 100years with the time horizon of 500-year in the Chapman-Richards simulation and in the lowest harvest intensity with the time horizon of 500-year in the FVS simulation. Based on the results, increasing growth rate, postponing harvest, reducing harvest intensity and increasing length of time horizon could reduce the impact of forest harvest on carbon sequestration. The method proposed in this study is more proper to assess the impact on carbon sequestration, and it has much wider applications in forest management practice. PMID- 28988095 TI - Assessing the resilience of urban areas to traffic-related air pollution: Application in Greater Paris. AB - Recent studies report that outdoor air pollution will become the main environmental cause of premature death over the next few decades (OECD, 2012; WHO, 2014; World Bank, 2016). Cities are considered hot spots and urban populations are particularly exposed. There is therefore an urgent need to adapt urban systems and urban design to tackle this issue. While most European cities have introduced measures to reduce emissions, action is still required to reduce concentrations and exposure, and a holistic approach to urban design is badly needed. The concept of urban resilience, defined by Holling (1987) as the ability of a city to absorb a disturbance while maintaining its functions and structures, may offer a new paradigm for tackling urban air pollution. We propose to adapt the concept of urban resilience to outdoor air pollution. A method has been developed to assess the resilience of an urban area to outdoor air pollution. Three "resilience capacities" have been identified: the capacity of an urban area to decrease air pollution emissions, the capacity to decrease concentrations and the capacity to decrease exposure. The calculation is based on the analysis of urban design, defined as the pattern of buildings as well as the structural elements that define an urban area (urban morphology; transport network, services and land use). For each resilience capacity, indicators are calculated using a Geographic Information System (GIS) and a grid-based approach. This method has been implemented in the Greater Paris area within a 500m grid-cell system. Greater Paris is one of the densest urban areas in Europe and experiences high air pollution levels. The proposed "quick scan" method helps to localize areas where specific action is needed. PMID- 28988096 TI - Bridging environmental and financial cost of dairy production: A case study of Irish agricultural policy. AB - The Irish agricultural policy 'Food Harvest 2020' is a roadmap for sectoral expansion and Irish dairy farming is expected to intensify, which could influence the environmental and economic performance of Irish milk production. Evaluating the total environmental impacts and the real cost of Irish milk production is a key step towards understanding the possibility of sustainable production. This paper addresses two main issues: aggregation of environmental impacts of Irish milk production by monetization, to understand the real cost of Irish milk production, including the environmental costs; and the effect of the agricultural policy 'Food Harvest 2020' on total cost (combining financial cost and environmental cost) of Irish milk production. This study used 2013 Irish dairy farming as a baseline, and defined 'bottom', 'target' and 'optimum' scenarios, according to the change of elementary inputs required to meet agricultural policy ambitions. The study demonstrated that the three monetization methods, Stepwise 2006, Eco-cost 2012 and EPS 2000, could be used for aggregating different environmental impacts into monetary unit, and to provide an insight for evaluating policy related to total environmental performance. The results showed that the total environmental cost of Irish milk production could be greater than the financial cost (up to ?0.53/kg energy corrected milk). The dairy expansion policy with improved herbage utilization and fertilizer application could reduce financial cost and minimize the total environmental cost of per unit milk produced. PMID- 28988097 TI - No evidence of increased growth or mortality in fish exposed to oxazepam in semi natural ecosystems. AB - An increasing number of short-term laboratory studies on fish reports behavioral effects from exposure to aquatic contaminants or raised carbon dioxide levels affecting the GABAA receptor. However, how such GABAergic behavioral modifications (GBMs) impact populations in more complex natural systems is not known. In this study, we induced GBMs in European perch (Perca fluviatilis) via exposure to a GABA agonist (oxazepam) and followed the effects on growth and survival over one summer (70days) in replicated pond ecosystems. We hypothesized that anticipated GBMs, expressed as anti-anxiety like behaviors (higher activity and boldness levels), that increase feeding rates in laboratory assays, would; i) increase growth and ii) increase mortality from predation. To test our hypotheses, 480 PIT tagged perch of known individual weights, and 12 predators (northern pike, Esox lucius) were evenly distributed in 12 ponds; six control (no oxazepam) and six spiked (15.5+/-4MUgl-1 oxazepam [mean+/-1S.E.]) ponds. Contrary to our hypotheses, even though perch grew on average 16% more when exposed to oxazepam, we found no significant difference between exposed and control fish in growth (exposed: 3.9+/-1.2g, control: 2.9+/-1g [mean+/-1S.E.], respectively) or mortality (exposed: 26.5+/-1.8individuals pond-1, control: 24.5+/-2.6individuals pond-1, respectively). In addition, we show that reduced prey capture efficiency in exposed pike may explain the lack of significant differences in predation. Hence, our results suggest that GBMs, which in laboratory studies impact fish behavior, and subsequently also feeding rates, do not seem to generate strong effects on growth and predation-risk in more complex and resource limited natural environments. PMID- 28988098 TI - Multiple-pathway remediation of mercury contamination by a versatile selenite reducing bacterium. AB - Mercury contamination is a global concern because of its high toxicity, persistence, bioaccumulative nature, long distance transport and wide distribution in the environment. In this study, the efficiency and multiple pathway remediation mechanisms of Hg2+ by a selenite reducing Escherichia coli was assessed. E. coli can reduce Hg2+ to Hg+ and Hg0 and selenite to selenide at the same time. This makes a multiple-pathway mechanisms for removal of Hg2+ from water in addition to biosorption. It was found that when the original Hg2+ concentration was 40MUgL-1, 93.2+/-2.8% of Hg2+ was removed from solution by E. coli. Of the total Hg removed, it was found that 3.3+/-0.1% was adsorbed to the bacterium, 2.0+/-0.5% was bioaccumulated, and 7.3+/-0.6% was volatilized into the ambient environment, and most (80.6+/-5.7%) Hg was removed as HgSe and HgCl precipitates and Hg0. On one hand, selenite is reduced to selenide and the latter further reacts with Hg2+ to form HgSe precipitates. On the other hand Hg2+ is successively reduced to Hg+, which forms solid HgCl, and Hg0. This is the report on bacterially transformation of Hg2+ to HgSe, HgCl and Hg0 via multiple pathways. It is suggested that E. coli or other selenite reducing microorganisms are promising candidates for mercury bioremediation of contaminated wastewaters, as well as simultaneous removal of Hg2+ and selenite. PMID- 28988100 TI - "Silent" Sleep Apnea in Dentofacial Deformities and Prevalence of Daytime Sleepiness After Orthognathic and Intranasal Surgery. AB - PURPOSE: The purposes of this study were to determine the occurrence of undiagnosed "silent" obstructive sleep apnea (OSA) in dentofacial deformity (DFD) patients at initial surgical presentation and to report on the level of daytime sleepiness in DFD patients with OSA and chronic obstructive nasal breathing (CONB) after undergoing bimaxillary, chin, and intranasal surgery. MATERIALS AND METHODS: A retrospective cohort study of patients with a bimaxillary DFD and CONB was implemented. Patients were divided into those with no OSA (group I) and those with OSA (group II). Group II was further subdivided into patients referred with polysomnogram (PSG)-confirmed OSA (group IIa) and those with a diagnosis of OSA only after surgical consultation, airway evaluation, and a positive PSG (group IIb). Group II patients were analyzed at a minimum of 1 year after surgery (range, 1 to 10 years) for daytime sleepiness with the Epworth Sleepiness Scale. Patients with postoperative excessive daytime sleepiness were assessed for risk factors and continued need for OSA treatment. Patients in group II were studied to determine which DFD patterns were most associated with OSA. We compared the prevalence of OSA between our study population and the general population. RESULTS: Two hundred sixty-two patients met the inclusion criteria. Of these, 23% (60 of 262) had PSG-confirmed OSA (group II). This rate was much higher than that found in the general population. Of the patients, 7% (19 of 262) were known to have OSA at initial surgical consultation (group IIa). An additional 16% (41 of 262) were later confirmed by PSG to have OSA (group IIb). Patients with primary mandibular deficiency and short face DFDs were most likely to have OSA (P < .001 and P = .001, respectively). In group II, 91% (55 of 60) rated their daytime sleepiness as "not sleepy" at a minimum of 1 year after surgery. A significant association was found between group II patients with postoperative excessive daytime sleepiness ("sleepy" or "very sleepy") and a preoperative body mass index category of overweight (P = .026). CONCLUSIONS: Our study found silent OSA to be frequent in the DFD population. The prevalence of OSA in DFD patients exceeded that estimated in the general population, with retrusive jaw patterns most affected. In DFD patients also presenting with OSA and CONB, we confirmed low levels of daytime sleepiness long-term after simultaneous bimaxillary orthognathic, chin, and intranasal surgery. PMID- 28988099 TI - Chlorinated persistent organic pollutants in serum of New Zealand adults, 2011 2013. AB - A national survey was conducted in 2011-2013 to assess serum concentrations of persistent organic pollutants (POPs) in adult New Zealanders. Participants were randomly selected from the 2010 Electoral Roll within 64 demographic strata according to 4 age groups, 4 regions, 2 ethnic groups (Maori/non-Maori) and gender. Eligible subjects (n=734) donated up to 30ml of blood, after which serum was pooled (n=49) according to demographic strata prior to analysis by GC-HRMS. Associations between demographic variables (age, region, ethnicity, gender) and serum POPs were assessed using linear regression. The weighted geometric mean (GM) of PCDD/Fs was 5.3pg/g lipid toxic equivalents using the WHO 2005 toxic equivalence factors (TEQ05), which increased by age (3.2, 4.4, 4.8, and 8.1pg/g lipid for the 19-24, 25-34, 35-49, and 50-64year age groups, respectively). The weighted GM of dioxin-like PCBs was 1.4pg TEQ05/g lipid which also increased by age (0.82, 0.86, 1.4, and 2.3pg/g lipid for the same age groups, respectively). Of the detected OCPs, the highest concentration was observed for p,p'-DDE (weighted GM, 220ng/g lipid) followed by hexachlorobenzene (HCB; 7.3ng/g lipid), beta-HCH (7.0ng/g lipid), and dieldrin (4.7ng/g lipid). For most Cl-POPs, concentrations were lowest in the youngest age group, and were similar for men and women and Maori and non-Maori. Serum Cl-POPs were, on average, 50% lower than those measured 15years earlier in 1997. This survey provides evidence of declining serum concentrations of chlorinated POPs in the New Zealand adult population. Age was the most important determinant of POPs concentrations. Body burdens of PCDD/Fs and PCBs in New Zealand are relatively low by international comparison, while for OCPs they are similar or lower compared to those reported for other developed countries. PMID- 28988101 TI - Computed Tomography Characterization and Comparison With Polysomnography for Obstructive Sleep Apnea Evaluation. AB - PURPOSE: We hypothesized that computed tomography (CT) combined with portable polysomnography (PSG) might better visualize anatomic data related to obstructive sleep apnea (OSA). The present study evaluated the CT findings during OSA and assessed their associations with the PSG data and patient characteristics. PATIENTS AND METHODS: We designed a prospective cross-sectional study of patients with OSA. The patients underwent scanning during the awake state and apneic episodes. Associations of the predictor variables (ie, PSG data, respiratory disturbance index [RDI]), patient characteristics (body mass index [BMI], neck circumference [NC], and waist circumference [WC]), and outcome variables (ie, CT findings during apneic episodes) were assessed using logistic regression analysis. The CT findings during apneic episodes were categorized regarding the level of obstruction, single level (retropalatal [RP] or retroglossal [RG]) or multilevel (mixed RP and RG), degree of obstruction (partial or complete), and pattern of collapse (complete concentric collapse [CCC] or other patterns). RESULTS: A total of 58 adult patients with OSA were scanned. The mean +/- standard deviation for the RDI, BMI, NC, and WC were 41.6 +/- 28.55, 27.80 +/- 5.43 kg/m2, 38.3 +/- 4.3 cm, and 93.8 +/- 13.6 cm, respectively. No variables distinguished between the presence of single- and multilevel airway obstruction in the present study. A high RDI (>=30) was associated with the presence of complete obstruction and CCC (odds ratio 6.33, 95% confidence interval 1.55 to 25.90; and odds ratio 3.77, 95% confidence interval 1.02 to 13.91, respectively) compared with those with a lesser RDI. CONCLUSIONS: An increased RDI appears to be an important variable for predicting the presence of complete obstruction and CCC during OSA. Scanning during apneic episodes, using low-dose volumetric CT combined with portable PSG provided better anatomic and pathologic findings of OSA than did scans performed during the awake state. PMID- 28988102 TI - Number of illness episodes as predictor of residual symptoms in major depressive disorder. AB - Notwithstanding major depressive disorder (MDD) is a recurring and chronic condition, relatively few variables have consistently been shown to predict its course. Residual depressive symptoms may be associated with disability and functional impairment but few studies evaluated clinical correlates associated with these symptoms and their impact on functioning after adjustment for potential confounders. Therefore, our study aimed to investigate factors associated with residual depressive symptoms and their impact on the course of MDD. The sample consisted of 210 consecutive MDD euthymic outpatients (67.6% females; mean age = 52.1 +/- 15.5), admitted to the Section of Psychiatry, University of Genoa (Italy). Residuals depressive symptoms were significantly associated with female gender; use of short half-life benzodiazepines; longer duration of the current depressive episode; higher number of illness episodes; and higher duration of illness. Conversely, prior treatment with first-generation antipsychotics, later age of illness onset and first hospitalization were less frequently observed among patients with residual symptoms. After multivariate analyses, only duration of current illness episodes (beta = 0.003; p = <0.005) and substance abuse (beta = 0.042; p = <0.05) remained significantly associated with residual symptoms. Our findings indicate that residual depressive symptoms conferred a pernicious illness course in this specific cohort of MDD patients. Future trials mainly targeting these burdensome symptoms are warranted. PMID- 28988103 TI - Opioid tapering in patients with prescription opioid use disorder: A retrospective study. AB - BACKGROUND AND AIMS: Opioid use disorder (OUD) refers to a maladaptive pattern of opioid use leading to clinically significant impairment or distress. OUD causes, and vice versa, misuses and abuse of opioid medications. Clinicians face daily challenges to treat patients with prescription opioid use disorder. An evidence based management for people who are already addicted to opioids has been identified as the national priority in the US; however, options are limited in clinical practices. In this study, we aimed to explore the success rate and important adjuvant medications in the medication assisted treatment with temporary use of methadone for opioid discontinuation in patients with prescription OUD. METHODS: This is a retrospective chart review performed at a private physician office for physical medicine and rehabilitation. We reviewed all medical records dated between December 1st, 2011 and August 30th, 2016. The initial evaluation of the included patients (N=140) was completed between December 1st, 2011 and December 31st, 2014. They all have concumittant prescription OUD and chronic non-cancer pain. The patients (87 female and 53 male) were 46.7+/-12.7 years old, and had a history of opioid use of 7.7+/-6.1 years. All patients received the comprehensive opioid taper treatments (including interventional pain management techniques, psychotherapy, acupuncture, physical modalities and exercises, and adjuvant medications) on top of the medication assisted treatment using methadone (transient use). Opioid tapering was considered successful when no opioid medication was used in the last patient visit. RESULTS: The 140 patients had pain of 9.6+/-8.4 years with 8/10 intensity before treatment which decreased after treatment in all comparisons (p<0.001 for all). Opioids were successfully tapered off in 39 (27.9%) patients after 6.6+/ 6.7 visits over 8.8+/-7.2 months; these patients maintained opioid abstinence over 14.3+/-13.0 months with regular office visits. Among the 101 patients with unsuccessful opioid tapering, 13 patients only visited the outpatient clinic once. Significant differences were found between patients with and without successful opioid tapering in treatment duration, number of clinic visits, the use of mirtazepine, bupropion, topiramate, and trigger point injections with the univariate analyses. The use of mirtazepine (OR, 3.75; 95% CI, 1.48-9.49), topiramate (OR, 5.61; 95% CI, 1.91-16.48), or bupropion (OR, 2.5; 95% CI, 1.08 5.81) was significantly associated with successful opioid tapering. The associations remain significant for mirtazepine and topiramate (not bupropion) in different adjusted models. CONCLUSIONS: With comprehensive treatments, 27.9% of patients had successful opioid tapering with opioid abstinence for over a year. The use of mirtazepine, topiramate, or likely bupropion was associated with successful opioid tapering in the medication assisted treatment with temporary use of methadone. Opioid tapering may be a practical option and should be considered for managing prescription OUD. IMPLICATIONS: For patients with OUD, indefinite opioid maintenance treatment may not be necessary. Considering the ethical values of autonomy, nonmaleficence, and beneficence, clinicians should provide patients with OUD the option of opioid tapering. PMID- 28988104 TI - Sleep, widespread pain and restless legs - What is the connection? PMID- 28988105 TI - Broadening the fear-avoidance model of chronic pain? PMID- 28988106 TI - DCPP1 is the mouse ortholog of human PAUF that possesses functional analogy in pancreatic cancer. AB - Pancreatic adenocarcinoma upregulated factor (PAUF) overexpressed in pancreatic ductal adenocarcinoma (PDAC) plays a major role in tumor progression and metastasis by autocrine and paracrine manners. However, underlying molecular mechanism of PAUF functioning in pancreatic cancer are not fully understood yet. The objective of this study was to evaluate the potential of demilune cell and parotid protein 1 (DCPP1) as a putative mouse ortholog of human PAUF by sequence alignment and functional studies. Overexpression of mouse DCPP1 in Chinese hamster ovary (CHO) cells or pancreatic cancer cells increased cell proliferation, migration, invasion, and adhesion ability in vitro. Treatment of human pancreatic cancer cells with recombinant mouse DCPP1 elevated cell growth, motility, invasiveness, and adhesiveness. Mouse DCPP1 exerted its function on pancreatic cancer cells by activating intracellular signaling pathways involved in aggressive cancer phenotype of human pancreatic cancer cells. Moreover, subcutaneous injection of mice with DCPP1-overexpressing CHO cells increased tumor sizes. Taken together, we conclude that mouse DCPP1 is a multifunctional promoter of tumor growth through functional activation of pancreatic cancer cells, suggesting it to be an ortholog of human PAUF. PMID- 28988107 TI - Calcium-dependent protein kinase 21 phosphorylates 14-3-3 proteins in response to ABA signaling and salt stress in rice. AB - The calcium-dependent protein kinases (CDPKs) are a class of plant-specific kinase that directly bind Ca2+ and mediate the calcium-signaling pathways to play important physiological roles in growth and development. The rice genome contains 31 CDPK genes, one of which, OsCPK21, is known to modulate the abscisic acid (ABA) and salt stress responses in this crop; however, the molecular mechanisms underlying this regulation are largely unknown. In the present study, we performed yeast two-hybrid screening, glutathione S-transferase pull-down, co immunoprecipitation, and bimolecular fluorescence complementation assays to confirm the interaction between OsCPK21 and one of its putative targets, Os14-3-3 (OsGF14e). We used an in vitro kinase assay and site-directed mutagenesis to verify that OsCPK21 phosphorylates OsGF14e at Tyr-138. We used real-time PCR to reveal that several ABA and salt inducible genes were more highly expressed in the OsCPK21-OE and OsGF14e WT-OE plants than in the mutant OsGF14e Y138A-OE and wild-type plants. These results suggest that OsCPK21 phosphorylates OsGF14e to facilitate the response to ABA and salt stress. PMID- 28988108 TI - Salubrinal protects human skin fibroblasts against UVB-induced cell death by blocking endoplasmic reticulum (ER) stress and regulating calcium homeostasis. AB - The role of UVB in skin photo damages has been widely reported. Overexposure to UVB will induce severe DNA damages in epidermal cells and cause most cytotoxic symptoms. In the present study, we tested the potential activity of salubrinal, a selective inhibitor of Eukaryotic Initiation Factor 2 (eIF2) -alpha phosphatase, against UV-induced skin cell damages. We first exposed human fibroblasts to UVB radiation and evaluated the cytosolic Ca2+ level as well as the induction of ER stress. We found that UVB radiation induced the depletion of ER Ca2+ and increased the expression of ER stress marker including phosphorylated PERK, CHOP, and phosphorylated IRE1alpha. We then determined the effects of salubrinal in skin cell death induced by UVB radiation. We observed that cells pre-treated with salubrinal had a higher survival rate compared to cells treated with UVB alone. Pre-treatment with salubrinal successfully re-established the ER function and Ca2+ homeostasis. Our results suggest that salubrinal can be a potential therapeutic agents used in preventing photoaging and photo damages. PMID- 28988109 TI - Nuclear import inhibitor N-(4-hydroxyphenyl) retinamide targets Zika virus (ZIKV) nonstructural protein 5 to inhibit ZIKV infection. AB - In the absence of approved therapeutics, Zika virus (ZIKV)'s recent prolific outbreaks in the Americas, together with impacts on unborn fetuses of infected mothers, make it a pressing human health concern worldwide. Although a key player in viral replication in the infected host cell cytoplasm, ZIKV non-structural protein 5 (NS5) appears to contribute integrally to pathogenesis by localising in the host cell nucleus, in similar fashion to NS5 from Dengue virus (DENV). We show here for the first time that ZIKV NS5 is recognized with high nanomolar affinity by the host cell importin alpha/beta1 heterodimer, and that this interaction can be blocked by the novel DENV NS5 targeting inhibitor N-(4 hydroxyphenyl) retinamide (4-HPR). Importantly, we show that 4-HPR has potent anti-ZIKV activity at low MUM concentrations. With an established safety profile for human use, 4-HPR represents an exciting possibility as an anti-ZIKV agent. PMID- 28988110 TI - Biophysical control of the growth of Agrobacterium tumefaciens using extremely low frequency electromagnetic waves at resonance frequency. AB - Isolated Agrobacterium tumefaciens was exposed to different extremely low frequencies of square amplitude modulated waves (QAMW) from two generators to determine the resonance frequency that causes growth inhibition. The carrier was 10 MHz sine wave with amplitude +/-10 Vpp which was modulated by a second wave generator with a modulation depth of +/- 2Vpp and constant field strength of 200 V/m at 28 degrees C. The exposure of A. tumefaciens to 1.0 Hz QAMW for 90 min inhibited the bacterial growth by 49.2%. In addition, the tested antibiotics became more effective against A. tumefaciens after the exposure. Furthermore, results of DNA, dielectric relaxation and TEM showed highly significant molecular and morphological changes due to the exposure to 1.0 Hz QAMW for 90 min. An in vivo study has been carried out on healthy tomato plants to test the pathogenicity of A. tumefaciens before and after the exposure to QAMW at the inhibiting frequency. Symptoms of crown gall and all pathological symptoms were more aggressive in tomato plants treated with non-exposed bacteria, comparing with those treated with exposed bacteria. We concluded that, the exposure of A. tumefaciens to 1.0 Hz QAMW for 90 min modified its cellular activity and DNA structure, which inhibited the growth and affected the microbe pathogenicity. PMID- 28988111 TI - PAI-1/PIAS3/Stat3/miR-34a forms a positive feedback loop to promote EMT-mediated metastasis through Stat3 signaling in Non-small cell lung cancer. AB - AIM: This study intented to clarify the intracellular effect of PAI-1 on Non small cell lung cancer (NSCLC) metastasis and the precise mechanism involved. METHODS: The metastatic properties of NSCLC cells were determined by transwell assays and wound-healing assay in vitro. The mRNA and protein expressions of genes were analyzed by Real-time qPCR and western blot, respectively. Pulmonary metastasis model of NSCLC cells was established to evaluate the pro-metastasis effect of PAI-1 and anti-metastatic effect of miR-34a in vivo. The gene targets of miR-34a were confirmed by luciferase reporter assays. Chromatin immunoprecipitation assay was employed to detect the transcriptional regulation of miR-34a. Co-immunoprecipitation assay was performed to observe the interaction of proteins. RESULTS: PAI-1, which was elevated in NSCLC patients with recurrence and metastasis, augmented NSCLC metastasis and was negatively related to the prognosis of NSCLC. miR-34a, which was decreased in NSCLC patients with metastasis, attenuated NSCLC metastasis and was positively correlated with the prognosis of NSCLC. Moreover, PAI-1 was identified as the target gene of miR-34a and activated the Stat3 signaling pathway to promote epithelial-mesenchymal transition (EMT) in NSCLC cells. PAI-1 interacted with PIAS3 to regulate Stat3 dependent gene expression and miR-34a was transcriptionally suppressed by Stat3 to form a positive regulatory loop through Stat3 signaling. CONCLUSION: Our findings suggest that PAI-1 and miR-34a, which can be clinically utilized as biomarkers for the clinical prognosis or diagnosis of NSCLC, are potential targets for the treatment of NSCLC. PMID- 28988112 TI - Caerulin-induced pro-inflammatory response in macrophages requires TRAF3-p38 signaling activation. AB - Acute pancreatitis is a common threat to human health. Caerulin provokes severe inflammations, causing injuries to surrounding pancreatic cells. TNF receptor associated factor 3 (TRAF3) is a highly versatile regulator of immune response. The current study aims to understand the potential effect of TRAF3 on caerulin induced pro-inflammatory responses. In the primary-cultured mouse bone marrow derived macrophages (BMDMs), caerulin induced TRAF3 protein stabilization, which formed a complex with mitogen-activated protein kinase kinase 3 (MKK3) to mediate downstream p38 activation. Lentiviral shRNA-mediated TRAF3 stable knockdown significantly attenuated caerulin-induced MKK3-p38 activation and production of several key pro-inflammatory cytokines, including interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha) and IL-17. Remarkably, TRAF3 knockdown in caerulin-stimulated BMDMs also alleviated cytotoxicity to Panc02 and primary mouse pancreatic cells. Thus, TRAF3 is required for caerulin-induced p38 activation and macrophage-mediated pro-inflammatory responses. TRAF3 expression in macrophages could be a novel therapeutic target protein for the treatment of acute pancreatitis. PMID- 28988113 TI - Effects of dexamethasone on purinergic signaling in murine mast cells: Selective suppression of P2X7 receptor expression. AB - Mast cells express many different purinergic receptors, including ionotropic P2X4 and P2X7, which recognize the accumulation of extracellular ATP released from activated and/or damaged cells. This results in the stimulation of mast cell functions. In this study, we investigated the effects of dexamethasone (Dex), an anti-inflammatory glucocorticoid widely used for the treatment of allergic disease, on purinergic receptor expression in mouse bone marrow-derived mast cells (BMMCs). Treatment of BMMCs with Dex decreased P2X7 receptor mRNA levels in a time- and concentration-dependent manner without affecting the expression of other purinergic receptor subtypes. Accordingly, fluorescence-activated cell sorting analysis revealed that Dex treatment also decreased P2X7 receptor protein levels. This effect was mimicked by prednisolone, another anti-inflammatory glucocorticoid, and was inhibited by the glucocorticoid receptor antagonist mifepristone. Functionally, treatment of BMMCs with Dex impaired the P2X7 mediated rise in intracellular Ca2+ concentration, degranulation, and ethidium uptake, a response relevant to receptor-pore formation. Finally, oral administration of Dex to C57BL/6 mice in vivo resulted in a significant decrease in P2X7 receptor expression in peritoneal mast cells. These results suggest that reduction of P2X7 receptor expression in mast cells might be one of the anti allergic mechanisms of Dex. PMID- 28988114 TI - Regulatory effects of the AMPKalpha-SIRT1 molecular pathway on insulin resistance in PCOS mice: An in vitro and in vivo study. AB - In order to preliminarily explore the correlation between the AMPKalpha-SIRT1 pathway and insulin resistance and reproductive function in PCOS mice and find the pathogenesis molecular mechanism and potential therapeutic target of PCOS, we carried out in vitro study of human granulosa KGN cells and in vivo study of PCOS mouse model which was constructed with DHEA, and AICAR and Compound C were applied. We have found that SIRT1 and AMPKalpha expression in KGN cells gradually decreased as DHEA concentration increased; Mice of the PCOS model were in an obvious status of IR (P < 0.05). Granulosa cells in their ovarian were present in fewer numbers and were disorderly arranged, their numbers of immature follicles were significantly increased, and their AMPKalpha-SIRT1 pathways were down regulated. The AMPKalpha-SIRT1 pathway could be up-regulated after AICAR treatment, resulting in improved IR status (P < 0.0001); however, the abovementioned effect was blocked by Compound C. Thus we concluded that the AMPKalpha-SIRT1 molecular pathway may be a molecular mechanism of IR in PCOS and may serve as a therapeutic target for the development of potential treatments for improving metabolic and reproductive function in PCOS. PMID- 28988115 TI - A novel antimicrobial peptide isolated from centipede Scolopendra subspinipes mutilans stimulates neutrophil activity through formyl peptide receptor 2. AB - In this study, we identified scolopendrasin X, a novel antimicrobial peptide (AMP), from centipede Scolopendra subspinipes mutilans. Scolopendrasin X strongly stimulated mouse neutrophils, resulting in intracellular calcium increase, chemotactic migration through pertussis toxin-sensitive G-protein and phospholipase C pathway, and increased superoxide anion production in neutrophils. Target receptor for scolopendrasin X, formyl peptide receptor (FPR)2 mediated scolopendrasin X-induced neutrophil activation. Moreover, scolopendrasin X significantly blocked inflammatory cytokine production induced by lipopolysaccharide in mouse neutrophils. Taken together, our results suggest that the novel AMP scolopendrasin X can be used as a material to regulate neutrophil activity through FPR2. PMID- 28988116 TI - Macrophage C-type lectin is essential for phagosome maturation and acidification during Escherichia coli-induced peritonitis. AB - Sepsis is a life-threatening condition caused by an uncontrolled response to bacterial infection. Impaired bactericidal activity in the host is directly associated with severe sepsis; however, the underlying regulatory mechanism(s) is largely unknown. Here, we show that MCL (macrophage C-type lectin) plays a crucial role in killing bacteria during Escherichia coli-induced peritonitis. MCL deficient mice with E. coli-induced sepsis showed lower survival rates and reduced bacterial clearance when compared with control mice, despite similar levels of proinflammatory cytokine production. Although the ability of macrophages from MCL-deficient mice to kill bacteria was impaired, they showed normal phagocytic activity and production of reactive oxygen species. In addition, MCL-deficient macrophages showed defective phagosome maturation and phagosomal acidification after E. coli infection. Taken together, these results indicate that MCL plays an important role in host defense against E. coli infection by promoting phagosome maturation and acidification, thereby providing new insight into the role of MCL during pathogenesis of sepsis and offering new therapeutic options. PMID- 28988117 TI - Mas-Related G-Protein Coupled Receptors and Cowhage-Induced Itch. PMID- 28988118 TI - A low-cost and miniaturized potentiostat for sensing of biomolecular species such as TNF-alpha by electrochemical impedance spectroscopy. AB - Miniaturizing potentiostats, keeping their cost low and yet preserving full measurement characteristics (e.g. bandwidth, determination of capacitive/inductive contribution to sensor's impedance and parallel screening) is still an unresolved challenge in bioelectronics. In this work, the combination of simple analogue circuitry together with powerful microcontrollers and a digital filter implementation is presented as an alternative to complex and incomplete architectures reported in the literature. A low-cost acquisition electronic system fully integrated with a biosensors platform containing eight gold working microelectrodes and integrated reference and counter electrodes was developed and validated. The manufacturing cost of the prototype was kept below 300 USD. The performance of the proposed device was benchmarked against a commercial impedance analyzer through the electrochemical analysis of a highly sensitive biosensor for the detection of tumor necrosis factor alpha (TNF-alpha) within the randomly chosen range of 266pg/mL to 666ng/mL in physiological medium (PBS). A strong correlation between the outputs of both devices was found in a critical range of frequencies (1-10Hz), and several TNF-alpha cytokine concentrations were properly discriminated. These results are very promising for the development of low-cost, portable and miniaturized electrochemical systems for point-of-care and environmental diagnosis. PMID- 28988119 TI - Glucocorticoid treatment facilitates development of a metabolic syndrome in ovariectomized Macaca Mulatta fed a high fat diet. AB - Metabolic syndrome (MetS) is characterized by a cluster of key features, which include abdominal obesity, insulin resistance, hypertension, and dyslipidemia. The aim of this study was to assess the impact of elevated glucocorticoid levels on the development of MetS in middle-aged female rhesus monkeys (Macaca Mulatta) after ovariectomy. Six female ovariectomized rhesus monkeys (9-13years) were randomly assigned to either a control group (normal diet, n=3) or a group in which MetS was facilitated (n=3). The MetS group fed with HFD (15% fat) and received oral prednisone acetate treatment (50mg/day). After 24months, the GCs treatment was withdrawn with continuation of high-fat feeding for a further 12months. After 24months, the MetS group displayed a significant increase in body weight and abdominal circumference. Additionally, the MetS animals displayed abnormal serum lipids, insulin resistance and impaired glucose tolerance. Histology of liver biopsies indicated marked accumulation of lipid droplets in hepatocytes of MetS animals. Withdrawal of GCs treatment led to recovery from above-mentioned metabolic disorders. Whereas GCs treatment increased leptin expression, it lowered expression of adiponectin and other factors in adipose tissue. Expression of Hydroxy-steroid dehydrogenase-1 and glucose transporter type-4 in the livers of MetS animals were reduced. We conclude that in the context of high fat diet, high levels of exogenous GCs contribute to the development of MetS in non-human primates. PMID- 28988121 TI - A study on the independence of egocentric and allocentric neglect. AB - Currently there seems to be consensus that visuospatial neglect may involve egocentric and allocentric symptoms. However, the relation between the two is still discussed and models have been proposed based on the high correlation between allocentric and egocentric neglect symptoms. To analyze the relation between these two kinds of symptoms we developed a new paradigm. In contrast to previous paradigms, we varied the extension of the search field and we added centered reference targets to evaluate egocentric effects independent from allocentric effects. Patients with exclusively left-sided neglect (n = 15) and left-sided visual field deficit (VFD) (n = 9) were included. Right brain damaged patients (n = 15) and a healthy control (n = 15) acted as control groups. The results revealed egocentric inattention in VFD patients. Neglect patients suffered from egocentric and allocentric neglect, but we found no interaction between both kinds of impairments in the sense of a monotonous additive or multiplicative increase going from right to left in terms of egocentric and allocentric coordinates. On the contrary, at the outmost left allocentric and egocentric positions, the number of omissions did not increase, unlike in outmost right and centered positions. In conclusion, our experiment shows that egocentric and allocentric neglect can be clearly dissociated in neglect patients and do not interact. Inclusion of neglect patients with a VFD may lead to an artificial interaction between egocentric and allocentric symptoms and this may explain the differences with results of previous studies. PMID- 28988120 TI - Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. AB - Leflunomide, used for the treatment of rheumatoid arthritis, has been reported to cause severe liver problems and liver failure; however, the underlying mechanisms are not clear. In this study, we used multiple approaches including genomic analysis to investigate and characterize the possible molecular mechanisms of the cytotoxicity of leflunomide in hepatic cells. We found that leflunomide caused endoplasmic reticulum (ER) stress and activated an unfolded protein response, as evidenced by increased expression of related genes including CHOP and GADD34; and elevated protein levels of typical ER stress markers including CHOP, ATF-4, p eIF2alpha, and spliced XBP1. The secretion of Gaussia luciferase was suppressed in cells treated with leflunomide in an ER stress reporter assay. Inhibition of ER stress with an ER stress inhibitor 4-phenylbutyrate, and knockdown of ATF-4 and CHOP genes partially protected cells upon leflunomide exposure. In addition, both genomic and biochemical analyses revealed that JNK and ERK1/2 of MAPK signaling pathways were activated, and both contributed to the leflunomide induced cytotoxicity. Inhibiting JNK activation using a JNK inhibitor attenuated the ER stress and cytotoxicity of leflunomide, whereas inhibiting ERK1/2 using an ERK1/2 inhibitor or ERK1/2 siRNA increased the adverse effect caused by leflunomide, suggesting opposite roles for the two pathways. In summary, our data indicate that both ER stress and the activation of JNK and ERK1/2 contribute to leflunomide-induced cytotoxicity. PMID- 28988122 TI - Views of people with schizophrenia and their caregivers towards the needs for psychiatric rehabilitation in urban and rural areas of mainland China. AB - This qualitative study explores and compares the views of the individuals with schizophrenia and their caregivers in the urban and rural areas of Wuxi towards the needs for psychiatric rehabilitation. The results may more precisely guide the government and policy makers to tailor the corresponding strategies and services. With interview guides, individual face-to-face semi-structured interviews were conducted among a total of 16 participants (four people with schizophrenia and their caregivers in the urban areas and in the rural areas, respectively). All interviews were audio-recorded, transcribed, and analyzed using an inductive approach. The findings revealed commonalities and discrepancies on their views about the needs of rehabilitation interventions and community care, the healthcare resources for medication, the major factors of employment, and the support to caregivers for facilitating recovery. Some policy and service implications to promote psychiatric rehabilitation of the people with schizophrenia and their caregivers in Wuxi are discussed. With careful consideration of the possible socio-cultural differences, the findings may also serve as references for the related researchers and clinicians in other regions in China. PMID- 28988123 TI - The impact of lifetime PTSD on the seven-year course and clinical characteristics of OCD. AB - Research has suggested that the co-occurrence of PTSD in individuals with OCD is associated with more severe symptoms and less responsivity to empirically supported treatment as compared to individuals with OCD and no history of PTSD. However, much of this work has been limited by non-empirical case report design, cross-sectional and retrospective analyses, or small sample sizes. The current study extended this research by comparing the clinical characteristics of individuals with OCD with and without a lifetime PTSD diagnosis in a large, naturalistic, longitudinal sample over the course of seven years. At baseline, individuals with comorbid lifetime PTSD reported significantly more severe symptoms of OCD (including symptom levels and insight), lower quality of life, and higher rates of comorbid lifetime mood and substance use disorders than participants without lifetime PTSD. Further, individuals with comorbid OCD and lifetime PTSD reported significantly more severe OCD symptoms over the course of seven years than those without lifetime PTSD. These results are largely consistent with the existing literature and support the need to consider PTSD symptoms in the assessment and treatment of OCD. PMID- 28988124 TI - In vitro and in vivo evaluation of targeting tumor with folate-based amphiphilic multifunctional stabilizer for resveratrol nanosuspensions. AB - Resveratrol (RSV) nanosuspensions, with long term stability and targeting delivery ability, were designed and demonstrated by in vitro and in vivo model. The folate modified distearoylphosphatidyl ethanolamine-polyethylene glycol (DSPE PEG-FA), as target delivery carrier, was synthesized and confirmed by FTIR and 1H NMR. D-alpha-tocopherol polyethylene glycol 1000 succinate (TPGS) and DSPE-PEG-FA used as stabilizers formed two RSV nanosuspensions (RSV-NA and RSV-NB), which were prepared by anti-solvent precipitation method and optimized by central composite design-response surface model (CCD-RSM). The morphology of RSV nanosuspensions showed flake shapes and spherical shapes by SEM. And the distribution of particles was uniform by TEM and AFM. The two RSV nanosuspensions displayed an amorphous state, by XRPD and DSC determination. At room temperature, the optimum RSV nanosuspensions showed long term stability for 20days. The cell proliferation and morphology study revealed that the RSV nanosuspensions significantly enhanced the in vitro cytotoxicity against A549 cells in a dose- and time-dependent manner. The recommended safe concentration was 5MUM for in vitro study. In vivo studies of the two nanosuspensions also displayed higher antitumor efficacy by reduced tumor volume and weight. Compared with the saline group, the tumor inhibition ratio of the RSV-NA was 61.53+/-18.36% and RSV-NB was 64.61+/-21.13%. The mice weight of the RSV-NA group and RSV-NB group was also maintained constant increasing. These results demonstrated that TPGS and DSPE-PEG FA could be used as stabilizers for stable RSV nanosuspensions formulation with the potentiality for targeting delivery to human alveolar carcinoma cells with high stability and efficacy. PMID- 28988125 TI - Ionic interactions determine the morphology of dried alkali/liposome suspension droplets. AB - We sought to understand why saline drops produce intriguing patterns when drying in the presence of zwitterionic liposomes. Specifically, we would like to comprehend why the nature of such patterns is hierarchically driven by the Hofmeister series. The liposome suspension is made of 1,2-dimyristoyl-sn-glycero 3-phosphocholine (DMPC) with alkali metal chlorides. A complexity analysis of the patterns gives a fractal dimension around 1.71, which means that the drying process resembles a DLA mechanism. A physicochemical study, including the determination of zeta potential, molecular dynamics simulations, microrheology, and calorimetry, supports the fact that electrostatic interactions among head groups of phospholipids with alkali cations are the driven forces behind the assembling of the observed structures. Moreover, we found that the morphology of the dried droplets is sensitive to the substrate. Our findings could be used in a biological context, for example, to characterize cells in ionic media. PMID- 28988126 TI - Quantitative characterization of hepatitis delta virus genome edition by next generation sequencing. AB - AIM: To determine the capacity of next-generation sequencing (NGS) for quantifying edited and unedited HDV populations, and to confirm if edition is a general phenomenon taking place along the entire HDV region analyzed, as we previously reported (Homs M et al. PLoS One 2016, 11, e0158557). METHODS: Four serum samples from 4 patients with chronic HDV/HBV infection were included in the study. The region selected for analysis covered 360 nucleotides (nt), positions 910-1270 of the HDV genome, which included the HDAg ORF editing site (nt 1014 within codon 196). Quantification of edited and unedited genomes was performed by molecular cloning and Sanger sequencing and by NGS. To evaluate the reliability of the NGS values obtained, we combined a clone with an edited codon and one with an unedited codon in known percentages in a series of artificial mixtures, which were then analyzed by NGS. In addition, we determined the nt changes occurring over the complete amplified region after excluding the editing codon (196) to evaluate edition along it. RESULTS: In total, 11,208 quality-filtered sequences were obtained in the 4 samples. The 95% confidence intervals for the proportions of unedited populations by molecular cloning and NGS were overlapping, and those of cloning were wider, indicating that they are comparable and that NGS is more precise than cloning. Unedited genomes predominated over edited ones in all 4 samples analyzed by NGS and in 3 of the 4 samples analyzed by molecular cloning. In total, 83,276 quality-filtered sequences were obtained from the artificial mixtures. Percentages of the two viral populations detected by NGS in these mixtures were comparable to the expected percentages. Evaluation of edition along the HDV coding region showed that transitions were more frequent than transversions, accounting for 63.09% and 36.91%, respectively. Interestingly, among the 4 possible transition-type changes, G:A and A:G accounted for 73.86% of the total. CONCLUSION: Next-generation sequencing proved useful to quantify edited and unedited HDV genomes, and provided relevant information on the HDV quasispecies. PMID- 28988127 TI - Comparative genome analysis of novel Podoviruses lytic for hypermucoviscous Klebsiella pneumoniae of K1, K2, and K57 capsular types. AB - Hypermucoviscous (HV) strains of capsular types K1, K2 and K57 are the most virulent representatives of the Klebsiella pneumoniae species. Eight novel bacteriophages lytic for HV K. pneumoniae were isolated and characterized. Three bacteriophages, KpV41, KpV475, and KpV71 were found to have a lytic activity against mainly K. pneumoniae of capsular type K1. Two phages, KpV74, and KpV763 were lytic for K2 capsular type K. pneumoniae, and the phage KpV767 was specific to K57-type K. pneumoniae only. Two more phages, KpV766, and KpV48 had no capsular specificity. The phage genomes consist of a linear double-stranded DNA of 40,395-44,623bp including direct terminal repeats of 180-246 bp. The G + C contents are 52.3-54.2 % that is slightly lower than that of genomes of K. pneumoniae strains being used for phage propagation. According to the genome structures, sequence similarity and phylogenetic data, the phages are classified within the genus Kp32virus and Kp34virus of subfamily Autographivirinae, family Podoviridae. In the phage genomes, genes encoding proteins with putative motifs of polysaccharide depolymerase were identified. Depolymerase genes of phages KpV71 and KpV74 lytic for hypermucoviscous K. pneumoniae of K1 and K2 capsular type, respectively, were cloned and expressed in Escherichia coli, and the recombinant gene products were purified. The specificity and polysaccharide degrading activity of the recombinant depolymerases were demonstrated. PMID- 28988128 TI - The role of EscD in supporting EscC polymerization in the type III secretion system of enteropathogenic Escherichia coli. AB - The type III secretion system (T3SS) is a multi-protein complex that plays a central role in the virulence of many Gram-negative bacterial pathogens. In enteropathogenic Escherichia coli, a prevalent cause of diarrheal diseases, the needle complex base of the T3SS is formed by multi-rings: two concentric inner membrane rings made by the two oligomerizing proteins (EscD and EscJ), and an outer ring made of a single oligomerizing protein (EscC). Although the oligomerization activity of these proteins is critical for their function and can, therefore, affect the virulence of the pathogen, the mechanisms underlying the oligomerization of these proteins have yet to be identified. In this study, we report that the proteins forming the inner-membrane T3SS rings, EscJ and EscD proteins, are crucial for the oligomerization of EscC. Moreover, we elucidate the oligomerization process of EscD and determine the contribution of individual regions of the protein to its self-oligomerization activity. We show that the oligomerization motif of EscD is located at its N-terminal portion and that its transmembrane domain can self-oligomerize, thus contributing to the self oligomerization of the full-length EscD. PMID- 28988129 TI - Assessment of synergistic antibacterial activity of combined biosurfactants revealed by bacterial cell envelop damage. AB - Besides potential surface activity and some beneficial physical properties, biosurfactants express antibacterial activity. Bacterial cell membrane disrupting ability of rhamnolipid produced by Pseudomonas aeruginosa C2 and a lipopeptide type biosurfactant, BS15 produced by Bacillus stratosphericus A15 was examined against Staphylococcus aureus ATCC 25923 and Escherichia coli K8813. Broth dilution technique was followed to examine minimum inhibitory concentration (MIC) of both the biosurfactants. The combined effect of rhamnolipid and BS15 against S. aureus and E. coli showed synergistic activity by expressing fractional inhibitory concentration (FIC) index of 0.43 and 0.5. Survival curve of both the bacteria showed bactericidal activity after treating with biosurfactants at their MIC obtained from FIC index study as it killed >90% of initial population. The lesser value of MIC than minimum bactericidal concentration (MBC) of the biosurfactants also supported their bactericidal activity against both the bacteria. Membrane permeability against both the bacteria was supported by amplifying protein release, increasing of cell surface hydrophobicity, withholding capacity of crystal violet dye and leakage of intracellular materials. Finally cell membrane disruption was confirmed by scanning electron microscopy (SEM). All these experiments expressed synergism and effective bactericidal activity of the combination of rhamnolipid and BS15 by enhancing the bacterial cell membrane permeability. Such effect of the combination of rhamnolipid and BS15 could make them promising alternatives to traditional antibiotic in near future. PMID- 28988130 TI - KLF4 overcomes tamoxifen resistance by suppressing MAPK signaling pathway and predicts good prognosis in breast cancer. AB - Tamoxifen resistance represents a daunting challenge to the successful treatment for breast cancer. Kruppel-like factor 4 has critical roles in the development and progression of breast cancer, but its expression, function and regulation in the efficacy of TAM therapy in breast cancer have yet to be investigated. Here, we examined the clinical significance and biologic effects of KLF4 in breast cancer. Firstly, higher expression of KLF4 correlated with increased TAM sensitivity in breast cancer cells, and analysis of GEO datasets indicated that KLF4 expression was positively correlated with ERalpha and enhanced expression of KLF4 sensitized breast cancer patients to endocrine therapy. Knockdown of KLF4 in MCF-7 and BCAP37 cells led to increased TAM resistance, while ectopic KLF4 expression promoted the responsiveness to TAM in T47D and TAM-resistant MCF-7/TAM cells. Secondly, ectopic KLF4 overexpression suppressed MCF-7/TAM cell growth, invasion and migration. Moreover, KLF4 expression was down-regulated in breast cancer tumor tissues and high expression of KLF4 was associated with favorable outcomes. Mechanistically, KLF4 may enhance the responsiveness of breast cancer cells to TAM through suppressing mitogen-activated protein kinase (MAPK) signaling pathway. We found that ERK and p38 were more activated in MCF-7/TAM compared with MCF-7, and treatment with MAPK-specific inhibitors significantly suppressed cell viability. Knockdown of KLF4 activated ERK and p38 and drove MCF 7 cells to become resistant to TAM. Conversely, overexpression of KLF4 in MCF 7/TAM cells suppressed ERK and p38 signaling and resulted in increased sensitivity to TAM. Therefore, our findings suggested that KLF4 contributed to TAM sensitivity in breast cancer via phosphorylation modification of ERK and p38 signaling. Collectively, this study highlighted the significance of KLF4/MAPK signal interaction in regulating TAM resistance of breast cancer, and suggested that targeting KLF4/MAPK signaling may be a potential therapeutic strategy for breast cancer treatment, especially for the TAM-resistant patients. PMID- 28988131 TI - Ovariectomy influences the circadian rhythm of locomotor activity and the photic phase shifts in the volcano mouse. AB - Recently, the relationship between the circadian system and female reproduction has been of great interest; ovarian hormones can modify the amount and distribution of daily activity differently in rodent species. The volcano mouse Neotomodon alstoni is a species in which it is possible to study the circadian rhythm of locomotion, and it offers comparative information about the influence of ovaries on the circadian system. In this study, we used infrared crossings to compare free movement in intact and sham-operated or ovariectomized mice. We analyzed behavioral and endocrine changes related to the estrous cycle and locomotor circadian rhythm in free-running mice and photic phase shifting. Evidence shows that intact mice present a scalloped pattern of daily activity during the estrous cycle. In constant darkness, the ovariectomy reduces the total amount of activity, shortens the free-running circadian period of locomotion and increases photic phase shifts during the early subjective night. During entrainment, the ovariectomized mice increased the amplitude of total activity during the scotophase, and delay the time of activity onset. These results suggest that ovarian hormones in N. alstoni modulate the circadian rhythm of locomotor activity in a species-specific manner. PMID- 28988132 TI - Ferulic acid attenuates diabetes-induced cognitive impairment in rats via regulation of PTP1B and insulin signaling pathway. AB - Cognitive impairment has been recognized as a typical characteristic of neurodegenerative disease in diabetes mellitus (DM) and this cognitive dysfunction may be a risk factor for Alzheimer's disease (AD). Ferulic acid, a phenolic compound commonly found in a range of plants, has emerged various properties including anti-inflammatory and neuroprotective effects. In the present study, the protective activities and relevant mechanisms of ferulic acid were evaluated in diabetic rats with cognitive deficits, which were induced by a high-glucose-fat (HGF) diet and low dose of streptozotocin (STZ). It was observed that ferulic acid significantly increased body weight and decreased blood glucose levels. Meanwhile, ferulic acid could markedly ameliorate spatial memory of diabetic rats in Morris water maze (MWM) and decrease AD-like pathologic changes (Abeta deposition and Tau phosphorylation) in the hippocampus, which might be correlated with the inhibition of inflammatory cytokines release and reduction of protein tyrosine phosphatase 1B (PTP1B) expression. Moreover, the levels of brain insulin signal molecules p-IRS, p-Akt and p-GSK3beta were also investigated. We found that ferulic acid administration restored the alterations in insulin signaling. In conclusion, ferulic acid exhibited beneficial effects on diabetes induced cognition lesions, which was involved in the regulation of PTP1B and insulin signaling pathway. We suppose that PTP1B inhibition may represent a promising approach to correct abnormal signaling linked to diabetes-induced cognitive impairment. PMID- 28988134 TI - Dynamics of large-scale electrophysiological networks: A technical review. AB - For several years it has been argued that neural synchronisation is crucial for cognition. The idea that synchronised temporal patterns between different neural groups carries information above and beyond the isolated activity of these groups has inspired a shift in focus in the field of functional neuroimaging. Specifically, investigation into the activation elicited within certain regions by some stimulus or task has, in part, given way to analysis of patterns of co activation or functional connectivity between distal regions. Recently, the functional connectivity community has been looking beyond the assumptions of stationarity that earlier work was based on, and has introduced methods to incorporate temporal dynamics into the analysis of connectivity. In particular, non-invasive electrophysiological data (magnetoencephalography/electroencephalography (MEG/EEG)), which provides direct measurement of whole-brain activity and rich temporal information, offers an exceptional window into such (potentially fast) brain dynamics. In this review, we discuss challenges, solutions, and a collection of analysis tools that have been developed in recent years to facilitate the investigation of dynamic functional connectivity using these imaging modalities. Further, we discuss the applications of these approaches in the study of cognition and neuropsychiatric disorders. Finally, we review some existing developments that, by using realistic computational models, pursue a deeper understanding of the underlying causes of non-stationary connectivity. PMID- 28988133 TI - Coupling between physiological TSPO expression in brain and myocardium allows stabilization of late-phase cerebral [18F]GE180 PET quantification. AB - OBJECTIVES: PET imaging of the 18 kDa translocator protein (TSPO), a biomarker of microglial activity, receives growing interest in clinical and preclinical applications of neuroinflammatory and neurodegenerative brain diseases. In globally affected brains, intra-cerebral pseudo reference regions are not feasible. Consequently, many brain-independent approaches have been attempted, including SUV analysis and normalization to muscle- or heart uptake, aiming to stabilize quantitative analysis. In this study, we systematically compared different image normalization methods for static late phase TSPO-PET imaging of rodent brain. METHODS: We first obtained gamma counter measurements for gold standard quantitation of [18F]GE180 uptake in brain of C57Bl/6 mice (N = 10) after PET, aiming to identify factors contributing significantly to the quantitative results. Subsequently, data from a large cohort of C57Bl/6 mice (N = 79) were compiled to precisely determine the weighted influence and variance attributable these factors by regression analysis. Scan-rescan variability and agreement with histology were used to validate the tested normalization methods in an Alzheimer's disease (AD) mouse model with pathologically increased TSPO expression (PS2APP; N = 24). Longitudinal data from AD model mice (N = 10) scanned at four different ages were used to challenge and validate the different normalization methods in a practical application. RESULTS: Gamma counter results revealed that injected dose, body weight and PET-measured radioactivity concentration in the ventral myocardium all significantly accounted for [18F]GE180 activity in the brain. Skeletal muscle activity had high test-retest variance in this PET only application and was therefore pursued no further. Regression analysis of the large scale evaluation showed that scaling to injected dose or SUV analysis accounted for little variance in brain activity (R2 < 0.5), but inclusion of myocardial activity together with injected dose and body weight in the regression model accounted for most of the variance in brain uptake (R2 = 0.94). Scan-rescan stability, correlation with histology and applicability for longitudinal examination in the disease model were also significantly improved by inclusion of myocadial uptake in the quantitative model. CONCLUSION: Cerebral and myocardial TSPO expression are highly coupled under physiological conditions. Myocardial uptake has great potential for stabilization of static late phase [18F]GE180 quantification in brain in the absence of a valid intra-cerebral pseudo-reference region. PMID- 28988135 TI - Skin fluorescence following photodynamic therapy with NPe6 photosensitizer. AB - BACKGROUND: The second-generation photosensitizer NPe6 has strong anti-tumor effects with a much shorter photosensitive period than the first-generation photosensitizer Photofrin. Although photosensitive period has been reduced, skin photosensitivity is still a major side effect of photodynamic therapy (PDT). Therefore, we conducted a prospective study to investigate whether the NPe6 fluorescence intensity in skin after PDT could be measured effectively in human patients to improve the management of a patient's photosensitive period. METHODS: The NPe6 fluorescence measurements using a constructed fluorescence sensing system at the inside of the arm were acquired prior to and 5 and 10min after NPe6 administration as well as at the time of PDT (4-5h after administration), at discharge (2 or 3days after PDT), and at 1 or 2 weeks after PDT. Participants were interviewed as to whether they had any complications at 2 weeks after PDT. RESULTS: Nine male patients and one female patient entered this study. Nine patients were inpatients and one patient was an outpatient. All of the measurements of NPe6 fluorescence in the skin could be obtained without any complications. The spectral peak was detected at the time of discharge (2-3days after administration) in most cases and it decreased at 1 or 2 weeks after PDT. CONCLUSIONS: The fluorescence of NPe6 in the skin could be detected feasibly using the fluorescence sensing system in human patients. Measuring the relative concentration of NPe6 in the skin indirectly by measuring fluorescence intensity might be useful to predict the period of skin photosensitivity after PDT. PMID- 28988136 TI - Effect of natural polyphenol on the oxidative stability of pecan oil. AB - We evaluated the antioxidant activity of natural polyphenols which gives high oxidative stability to the pecan oil. The in vitro DPPH radical scavenging, reducing power and total antioxidant activity of tested antioxidants demonstrated that tannic acid displayed the highest DPPH scavenging activity and provided the largest reducing power. During storage of pecan oil, based on oxidative stability tests, we further evaluated the protective effect of polyphenols and synthetic antioxidants on the oxidative stability of pecan oil. The results showed that caffeic acid inhibited oxidation of pecan oil effectively. Sesamol and catechin showed slight improvement in oxidative stability, while ferulic acid, erucic acid and rutin had no effect. Taken together, compared with synthetic antioxidants (TBHQ, BHT, BHA), caffeic acid was observed to be stronger than BHT and BHA and was close to TBHQ. PMID- 28988137 TI - RIFM fragrance ingredient safety assessment, cis-6-nonen-1-ol, CAS Registry Number 35854-86-5. PMID- 28988138 TI - MouseTox: An online toxicity assessment tool for small molecules through Enalos Cloud platform. AB - Advances in the drug discovery research substantially depend on in silico methods and techniques that capitalize on experimental data to enable the accurate property/activity assessment by employing a variety of computational techniques. These in silico tools can significantly reduce expensive and time consuming experimental procedures required and are strongly recommended to avoid animal testing, especially as far as toxicity evaluation and risk assessment is concerned. In this context, in the present work we aim to develop a predictive model for the cytotoxic effects of a wide range of compounds based solely on calculated molecular descriptors that account for their topological, geometric and structural characteristics. The developed model was fully validated and was released online via Enalos Cloud platform accessible through http://enalos.insilicotox.com/MouseTox/. This ready-to-use web service offers, through a user-friendly interface, free access to the model results and therefore can act as a toxicity prediction tool for the risk assessment of novel compounds, without any special requirements or prior programming skills. PMID- 28988139 TI - RIFM fragrance ingredient safety assessment, beta-methylphenethyl alcohol, CAS Registry Number 1123-85-9. PMID- 28988140 TI - RIFM fragrance ingredient safety assessment, alpha-Propylphenethyl alcohol, CAS Registry Number 705-73-7. PMID- 28988141 TI - Ultrasonic wavefield inversion and migration in complex heterogeneous structures: 2D numerical imaging and nondestructive testing experiments. AB - Delaminations, cracks and other defects in engineered structures often lie close to the theoretical resolution limit for ultrasonic waves. While ultrasonic waveform tomography has succeeded in detecting such features, recovery is difficult because it requires computationally expensive high-frequency numerical wave simulations and an accurate understanding of large-scale background variations of the engineered structure. Without such knowledge, small defects may be incorrectly imaged or go undetected altogether. To reduce computational cost and improve detection of small defects, a useful approach is to divide the waveform tomography procedure into two steps: first, a low-frequency model building step aimed at recovering background structure, and second, a high frequency imaging step targeting defects. The first is naturally formulated as waveform inversion for wavespeed parameters and the second as time reversal migration for reflectivity. Through synthetic test cases, we show that the two step workflow appears more promising in most cases than a single-step inversion. In particular, we find that new workflow succeeds in the challenging scenario where the defect lies along preexisting layer interface in a composite bridge deck and in related experiments involving noisy data or inaccurate source parameters. PMID- 28988142 TI - Effective and rapid technique for temporal response modeling of surface acoustic wave interdigital transducers. AB - Surface Acoustic Wave Interdigital Transducers (SAW-IDT) has a considerable application potential for characterization of properties of thin layers, coatings and functional surfaces. For optimization of these SAW-IDTs, it is necessary to study various SAW-IDT configurations by varying the number of electrodes, dimensions of the electrodes, their shapes and spacings. The finite element method (FEM) is generally used to model such transducers but results are obtained in several hours (or days). Thus it is necessary to implement effective and rapid technique for SAW-IDT modeling. In this study, we develop simulation tool based on Spatial Impulse Response model. Therefore, we reduce considerably computing time and results are obtained in a few seconds. In order to validate this method, theoretical and experimental results are compared with finite element method. The results obtained show a good concordance and confirm effectiveness of suggested method. In additional, this method requires less computer memory. PMID- 28988143 TI - Fatigue failure load of zirconia-reinforced lithium silicate glass ceramic cemented to a dentin analogue: Effect of etching time and hydrofluoric acid concentration. AB - This study aimed to evaluate the effect of etching time and hydrofluoric acid (HF) concentration on the fatigue failure load and surface characteristics of zirconia-reinforced lithium silicate glass (ZLS) ceramic cemented to a dentin like, fiber reinforced epoxy resin. Ceramic (Suprinity, VITA) (1.0mm thick) and epoxy resin (2.5mm thick) discs (10mm diameter) were produced. The bonding surface of the ceramic samples was nonetched (control group), or etched for 30, 60 or 90s by 5% or 10% HF. The epoxy resin discs were etched by 10% HF for 30s followed by the application of an adhesive material (Single Bond Universal, 3M ESPE). Pairs of ceramic/epoxy resin discs were cemented with a dual cure resin cement. The fatigue failure load was determined by the staircase method (500,000 cycles at 20Hz; initial load = 925N; step size = 45N). In 10% HF the etching time was shown to influence the fatigue failure load, which increased as the etching time increased (30s < 60s < 90s), and in 5% HF the fatigue failure load was not shown to be affected by the etching time; the lowest fatigue failure loads were produced in the control group without ceramic etching followed by 10% HF acid etching for 30s. Topography analysis showed variations based on the etching protocols. All fractures (radial cracks) were shown to originate from defects at the ceramic surface on the cementing interface. For fatigue loading improvements of ZLS ceramic, 10% HF acid etching for 90s and silanization of the ceramic surface is recommended. PMID- 28988144 TI - Intracelluar delivery of A20 protein inhibits TNFalpha-induced NF-kappaB activation. AB - A20 (also known as TNFAIP3) is a potent anti-inflammatory protein that suppresses many intracellular signaling pathways induced by inflammatory cytokines and bacterial and viral pathogens. The anti-inflammatory function of A20 depends on its modulation of or binding to polyubiquitin chains on key signaling proteins in the nuclear factor-kappaB (NF-kappaB) pathway. To test whether A20 can be used as therapeutic agent in these inflammatory diseases, we prepared a recombinant cell penetrating form of A20 (TAT-A20) for intracellular delivery and examined its effect on tumor necrosis factor-alpha (TNFalpha)-induced NF-kappaB activation. We observed that TAT-A20 was effectively transduced into cells within 30 min, whereas A20 protein without TAT motive was not. TAT-A20 also inhibited NF-kappaB induction in fibroblasts stimulated with TNFalpha. These results suggest that increasing intracellular level of A20 can be an effective means to suppress NF kappaB activation and treat inflammatory diseases. PMID- 28988145 TI - Heterologous expression of Homo sapiens alpha-folate receptors in E. coli by fusion with a trigger factor for enhanced solubilization. AB - The role of Alpha folate receptors (FRalpha) in folate metabolism and cancer development has been extensively studied. The reason for this is not only associated to its direct relation to disease development but also to its potential use as a highly sensitive and specific biomarker for cancers therapies. Over the recent years, the crystal structures of human FRalpha complexed with different ligands were described relying on an expensive and time-consuming production process. Here, we constructed an efficient system for the expression and purification of a human FRalpha in E. coli. Unlike a conventional expression method we used a specific protein fusion expressing the target protein together with a trigger factor (TF). This factor is a chaperone from E. coli that assists the correct folding of newly synthesized polypeptide chains. The activity of rTFFRalpha was comparable to glycosylphosphatidylinositol (GPI) anchored proteins extracted from HeLa tumor cells. Our work demonstrates a straightforward and versatile approach for the production of active human FRalpha by heterologous expression; this approach further enhances the development of inhibition studies and biotechnological applications. The purified product was then conjugated to liposomes, obtaining a 35% higher signal from densitometry measurement on the immunoblotting assay in the contruct containing the Ni-NTA tag, as a mimesis of an exosome, which is of vital importance to nanotherapeutic techniques associated to treatment and diagnosis of tumors. PMID- 28988147 TI - Selection bias in ecological studies. PMID- 28988146 TI - Recombinant production of the insecticidal scorpion toxin BjalphaIT in Escherichia coli. AB - Scorpion long-chain insect neurotoxins have important potential application value in agricultural pest control. The difficulty of obtaining natural toxins is the major obstacle preventing analyses of their insecticidal activity against more agricultural insect pests. Here we cloned the insect neurotoxin BjalphaIT gene into the pET32 expression vector and expressed the resulting thioredoxin (Trx) BjalphaIT fusion protein in Escherichia coli. Soluble Trx-BjalphaIT was expressed at a high level when induced at 18 degrees C with 0.1 mM isopropyl beta-d-1 thiogalactopyranoside, and it was purified by Ni2+-nitriloacetic acid affinity chromatography. After cleaving the Trx tag with recombinant enterokinase, the digestion products were purified by CM Sepharose FF ion-exchange chromatography, and 1.5 mg of purified recombinant BjalphaIT (rBjalphaIT) was obtained from 100 ml of induced bacterial cells. Injecting rBjalphaIT induced obvious neurotoxic symptoms and led to death in locust (Locusta migratoria) larvae. Dietary toxicity was not observed in locusts. The results demonstrate that active rBjalphaIT could be obtained efficiently from an E. coli expression system, which is helpful for determining its insecticidal activity against agricultural insect pests. PMID- 28988148 TI - The reach, adoption, and effectiveness of online training for healthcare professionals. PMID- 28988150 TI - Mesophyll cell ultrastructure of wheat leaves etiolated by lead and selenium. AB - The ultrastructure of mesophyll cells was studied in leaves of the Triticum aestivum L. cv. "Trizo" seedlings after two weeks of growth on soil contaminated by Pb and/or Se. The soil treatments: control; (Pb1) 50mgkg-1; (Pb2) 100mgkg-1; (Se1) 0.4mgkg-1; (Se2) 0.8mgkg-1; (Pb1+Se1); (Pb1+Se2); (P2+Se1); and (Pb2+Se2) were used. Light and other conditions were optimal for plant growth. The (Se1) plants showed enhanced growth and biomass production; (Pb1+Se1)-plants did not lag behind the controls, though O2 evolution decreased; chlorophyll content did not differ statistically in these treatments. Other treatments led to statistically significant growth suppression, chlorophyll content reduction, inhibition of photosynthesis, stress development tested by H2O2 and leaf etiolation at the end of 14-days experiment. The tops of etiolated leaves remained green, while the main leaf parts were visually white. Plastids in mesophyll cells of etiolated parts of leaves were mainly represented by etioplasts and an insignificant amount of degraded chloroplasts. Other cellular organelles remained intact in most mesophyll cells of the plants, except (Pb2+Se2)-plants. Ruptured tonoplast and etioplast envelope, swelled cytoplasm and mitochondria, and electron transparent matrix of gialoplasm were observed in the mesophyll cells at (Pb2+Se2)-treatment, that caused maximal inhibition of plant growth. The results indicate that Pb and Se effects on growth of wheat leaves are likely to target meristem in which the development of proplastids to chloroplasts under the light is determined by chlorophyll biosynthesis. Antagonistic effect of low concentration of Se and Pb in combination may retard etiolation process. PMID- 28988149 TI - Neural dysfunction during temporal discounting in paediatric Attention Deficit/Hyperactivity Disorder and Obsessive-Compulsive Disorder. AB - Both Attention-Deficit/Hyperactivity Disorder (ADHD) and Obsessive-Compulsive Disorder (OCD) are associated with choice impulsivity, i.e. the tendency to prefer smaller immediate rewards over larger delayed rewards. However, the extent to which this impulsivity is mediated by shared or distinct underlying neural mechanisms is unclear. Twenty-six boys with ADHD, 20 boys with OCD and 20 matched controls (aged 12-18) completed an fMRI version of an individually adjusted temporal discounting (TD) task which requires choosing between a variable amount of money now or L100 in one week, one month or one year. Activations to immediate and delayed reward choices were compared between groups using a three-way ANCOVA. ADHD patients had steeper discounting rates on the task relative to controls. OCD patients did not differ from controls or patients with ADHD. Patients with ADHD and OCD showed predominantly shared activation deficits during TD in fronto striato-insular-cerebellar regions responsible for self-control and temporal foresight, suggesting that choice impulsivity is mediated by overlapping neural dysfunctions in both disorders. OCD patients alone showed dysfunction relative to controls in right orbitofrontal and rostrolateral prefrontal cortex, extending previous findings of abnormalities in these regions in OCD to the domain of choice impulsiveness. PMID- 28988151 TI - Does a lack of auditory experience affect sequential learning? AB - To understand the interaction between sensory experiences and cognition, it is critical to investigate the possibility that deprivation in one sensory modality might affect cognition in other modalities. Here we are concerned with the hypothesis that early experience with sound is vital to the development of domain general sequential processing skills. In line with this hypothesis, a seminal empirical study found that prelingually deaf children had impaired sequence learning in the visual modality. In order to assess the limits of this hypothesis, the current study employed a different visual sequence learning task in an investigation of prelingually deaf children with cochlear implants and normal hearing children. Results showed statistically significant learning in each of the two groups, and no significant difference in the amount of learning between groups. Moreover, there was no association between the age at which the child received their implant (and thus access to electric hearing) and their performance on the sequential learning task. We discuss key differences between our study and the previous study, and argue that the field must reconsider claims about domain-general cognitive impairment resulting from early auditory deprivation. PMID- 28988152 TI - Acute effects of static stretching on the shear elastic moduli of the medial and lateral gastrocnemius muscles in young and elderly women. AB - PURPOSE: Generally, static stretching (SS) is the recommended intervention for a decline in the range of motion among elderly adults. However, no study has investigated the acute effects of SS on the shear elastic modulus in elderly people. The aims of the present study were to investigate the acute effects of SS on the shear elastic moduli of the medial and lateral gastrocnemius muscles and to examine the differences in these acute effects between young and elderly women. METHODS: This study included 15 healthy young women (age: 23.1 +/- 3.4 years) and 15 healthy elderly women (age: 75.9 +/- 2.8 years) with no history of neuromuscular disease or musculoskeletal injury involving the lower limbs. The shear elastic moduli of the medial and lateral gastrocnemius muscles (MG and LG, respectively) were measured using ultrasound shear wave elastography at 30 degrees plantar flexion, 0 degrees , and 20 degrees dorsiflexion before and immediately after 5 min of SS with the knee extended. RESULTS: The shear elastic moduli of the MG and LG in all ankle position decreased after SS in both the young and elderly women, and there were no significant differences in the percent changes in the shear elastic moduli of the MG and LG at all ankle positions between the young and elderly women. CONCLUSIONS: These results suggested that 5 min of SS might be effective for decreasing shear elastic modulus in both young and elderly women and that the effects on shear elastic modulus are similar between young and elderly women. PMID- 28988153 TI - Synthesis and antimalarial evaluation of artesunate-polyamine and trioxolane polyamine conjugates. AB - A series of artesunate-polyamine and trioxolane-polyamine conjugates have been prepared. The conjugates were evaluated for antimalarial activity towards the K1 dual drug resistant and NF54 chloroquine-sensitive strains of Plasmodium falciparum (Pf) and for cytotoxicity towards the rat myoblast cell line L6. (Bis) Boc-(bis)-artesunate-polyamine and (tetra)-artesunate-polyamine conjugates exhibited potent in vitro activity towards both strains of Pf, with IC50 values in the range of 0.3-1.1 nM, comparable to the parent artesunate. Cytotoxicity within this series of analogues typically increased with polyamine (PA) chain length, identifying the PA3-4-3 (spermine), and to some extent the PA3-7-3 series, as being highly selective towards the parasite. The corresponding series of (bis)-Boc-(bis)-trioxolane and (tetra)-trioxolane-polyamine conjugates were less active as antimalarials than the parent trioxolane acid, highlighting the limitation of using this warhead for drug-conjugate studies. Preliminary in vivo evaluation of two artesunate-polyamine conjugates 11 and 16 demonstrated 95.5 99.8% reduction in parasitaemia with maximal 30 day survival rates (ip delivery). Oral testing of 11 proved less efficacious, with 95.7% activity and inconsistent survival rates of 16-30 days. In contrast, trioxolane-polyamines were substantially less effective (ip delivery), exhibiting only modest reductions in parasitaemia and modest to no increase in survival rates. PMID- 28988154 TI - Checking the detail in retail: Occurrence of Cryptosporidium and Giardia on vegetables sold across different counters in Chandigarh, India. AB - Fresh produce has been recognized as a vehicle of infection for protozoan parasites, particularly Cryptosporidium, and, to a lesser extent, Giardia. For both parasites, outbreaks associated with fresh produce have been documented. Although documented outbreaks tend to be from industrialized countries, contamination of fresh produce with these parasites is a global issue. In developing countries, infections with these parasites are often endemic in the community, and basic infrastructure and hygiene measures may be inadequate, thus the likelihood of contamination of fresh produce with these parasites may be higher. Realization of the importance of this transmission route comes against a backdrop of raw salads and more Western culinary habits gaining a foothold, and fresh produce being encouraged as part of the diet due to their associated health benefits. However, if consumption of uncooked fresh produce is going to increase its market sector in India, it is important that it is safe. In this study, various types of fresh produce obtained from three types of vendors in Chandigarh, a major city in Northern India, were analyzed for contamination with Cryptosporidium oocysts and Giardia cysts using a method that has been previously validated in inter-laboratory spiking experiments. A total of 284 samples of different fresh produce items were analyzed, obtained from the different retailers situated in different societal layers of the city. The overall prevalence of contamination of fresh produce with these parasites was just under 11%, with 6% of the vegetables contaminated with Cryptosporidium oocysts, and 5% with Giardia cysts. Contaminated vegetables included turnip, cabbage, carrot, chili, coriander, cucumber, radishes, and tomatoes. Molecular analyses identified contamination with Cryptosporidium parvum and Giardia duodenalis of Assemblage A and Assemblage D, indicating that contamination from animals may be of relevance. Although the prevalence of contamination is similar to those reported in previous studies, the levels of contamination on some items of fresh produce were relatively high. Although the different socioeconomic areas of Chandigarh from which the samples were obtained was not associated with likelihood of contamination, fresh produce from supermarkets had heavier contamination with Cryptosporidium oocysts than fresh produce purchased through other sales outlets. The results are discussed in relation to the fresh produce chain and sales models in Chandigarh, both in terms of where contamination may occur and the potential importance of fresh produce as a transmission vehicle. PMID- 28988155 TI - Optical and structural investigation on sodium borosilicate glasses doped with Cr2O3. AB - In this work, Sodium borosilicate glasses with chemical composition of 60% SiO2 20% B2O3-20%Na2O doped with different contents of Cr2O3 were prepared by melting quenching method. Physical, structural and optical properties of glasses were investigated by studying density and molar volume, Fourier Transform Infrared (FT IR) Spectra and UV-visible absorption spectroscopy. The results showed an increase in density of glasses with the increase of Cr2O3 that can be due to addition of oxide with high molar mass. The optical absorption spectra of un doped glass reveals UV absorption due to trace iron impurities with no visible band however Cr2O3 doped glasses shows absorption in visible range that are characteristic. Increasing of Cr3+ ions in the glassy microstructure of samples provides a semiconducting character to Sodium borosilicate glass by reducing the direct and indirect optical band gaps of glass samples from 3.79 to 2.59 (ev) and 3.36 to 2.09 (ev), respectively. These changes could be attributed to the role of Cr3+ ions as the network former which asserts improvement of semiconducting behavior in presence of Cr2O3. PMID- 28988156 TI - Antibiotic efficacy in the complex infection environment. AB - Accurate prediction of antimicrobial efficacy is essential for successful treatment of bacterial infection. Beyond genetically encoded mechanisms of antibiotic resistance, the determinants of antibiotic susceptibility during infection remain poorly understood, and treatment failure is common. Traditional antibiotic susceptibility testing fails to account for extrinsic determinants of antibiotic susceptibility present in the complex infection environment and is therefore a poor predictor of antibiotic treatment outcome. Here we discuss how host-pathogen interaction, microbial interspecies interaction, and metabolic heterogeneity contribute to the success or failure of antibiotic therapy. Consideration of these factors during the treatment of disease will improve our ability to successfully resolve recalcitrant bacterial infection and improve patient health. PMID- 28988157 TI - Short- and long-term mortality following bleeding events in patients undergoing percutaneous coronary intervention: insights from four validated bleeding scales in the CHAMPION trials. AB - AIMS: The aim of this study was to determine the prognostic significance of periprocedural bleeding based on various definitions on 30-day and one-year all cause mortality in patients undergoing routine or urgent percutaneous coronary intervention (PCI). METHODS AND RESULTS: In this exploratory analysis of 25,107 patients enrolled in the three phase-3 CHAMPION trials, we assessed the prognostic impact of four bleeding scales (GUSTO, TIMI, ACUITY, and BARC) at 48 hrs. Follow-up all-cause mortality data were available at 30 days in all three trials, and at one year in CHAMPION PCI and CHAMPION PLATFORM. Bleeding rates within 48 hrs of PCI were variably identified by each clinical definition (range: <0.5% to >3.5%). Severe/major bleeding, measured by all bleeding scales, and blood transfusion requirement were independently associated with increased mortality at 30 days and one year after PCI (p<0.001 for all associations). Mild/minor bleeding was not independently predictive of one-year mortality (p>0.07 for all associations). Each bleeding definition demonstrated only modest ability to discriminate 30-day and one-year mortality (adjusted C-statistics range: 0.49 to 0.67). CONCLUSIONS: Commonly employed clinical definitions variably identify rates of bleeding after PCI. Severe or major, but not mild or minor, bleeding is independently associated with increased 30-day and one-year mortality. These data may aid in selection of appropriate bleeding metrics in future clinical trials. PMID- 28988158 TI - Outcomes of oxygen saturation targeting during delivery room stabilisation of preterm infants. AB - OBJECTIVE: To determine the association between SpO2 at 5 min and preterm infant outcomes. DESIGN: Data from 768 infants <32 weeks gestation from 8 randomised controlled trials (RCTs) of lower (<=0.3) versus higher (>=0.6) initial inspiratory fractions of oxygen (FiO2) for resuscitation, were examined. SETTING: Individual patient analysis of 8 RCTs INTERVENTIONS: Lower (<=0.3) versus higher (>=0.6) oxygen resuscitation strategies targeted to specific predefined SpO2 before 10 min of age. PATIENTS: Infants <32 weeks gestation. MAIN OUTCOME MEASURES: Relationship between SpO2 at 5 min, death and intraventricular haemorrhage (IVH) >grade 3. RESULTS: 5 min SpO2 data were obtained from 706 (92%) infants. Only 159 (23%) infants met SpO2 study targets and 323 (46%) did not reach SpO280%. Pooled data showed decreased likelihood of reaching SpO280% if resuscitation was initiated with FiO2 <0.3 (OR 2.63, 95% CI 1.21 to 5.74, p<0.05). SpO2 <80% was associated with lower heart rates (mean difference -8.37, 95% CI -15.73 to -1.01, *p<0.05) and after accounting for confounders, with IVH (OR 2.04, 95% CI 1.01 to 4.11, p<0.05). Bradycardia (heart rate <100 bpm) at 5 min increased risk of death (OR 4.57, 95% CI 1.62 to 13.98, p<0.05). Taking into account confounders including gestation, birth weight and 5 min bradycardia, risk of death was significantly increased with time taken to reach SpO280%. CONCLUSION: Not reaching SpO280% at 5 min is associated with adverse outcomes, including IVH. Whether this is because of infant illness or the amount of oxygen that is administered during stabilisation is uncertain and needs to be examined in randomised trials. PMID- 28988159 TI - Chest compression during sustained inflation versus 3:1 chest compression:ventilation ratio during neonatal cardiopulmonary resuscitation: a randomised feasibility trial. AB - BACKGROUND: Current neonatal resuscitation guidelines recommend 3:1 compression:ventilation (C:V) ratio. Recently, animal studies reported that continuous chest compressions (CC) during a sustained inflation (SI) significantly improved return of spontaneous circulation (ROSC). The approach of CC during SI (CC+SI) has not been examined in the delivery room during neonatal resuscitation. HYPOTHESIS: It is a feasibility study to compare CC+SI versus 3:1 C:V ratio during neonatal resuscitation in the delivery room. We hypothesised that during neonatal resuscitation, CC+SI will reduce the time to ROSC. Our aim was to examine if CC+SI reduces ROSC compared with 3:1 C:V CPR in preterm infants <33 weeks of gestation. STUDY DESIGN: Randomised feasibility trial. METHOD: Once CC was indicated all eligible infants were immediately and randomly allocated to either CC+SI group or 3:1 C:V group. A sequentially numbered, brown, sealed envelope contained a folded card box with the treatment allocation was opened by the clinical team at the start of CC. STUDY INTERVENTIONS: Infants in the CC+SI group received CC at a rate of 90/min during an SI with a duration of 20 s (CC+SI). After 20 s, the SI was interrupted for 1 s and the next SI was started for another 20 s until ROSC. Infants in the '3:1 group' received CC using 3:1 C:V ratio until ROSC. PRIMARY OUTCOME: Overall the mean (SD) time to ROSC was significantly shorter in the CC+SI group with 31 (9) s compared with 138 (72) s in the 3:1 C:V group (p=0.011). CONCLUSION: CC+SI is feasible in the delivery room. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT02083705, pre-results. PMID- 28988161 TI - Should tumbling E go out of date in amblyopia screening? Evidence from a population-based sample normative in children aged 3-4 years. AB - AIMS: To determine a normative of tumbling E optotype and its feasibility for visual acuity (VA) assessment in children aged 3-4 years. METHODS: A cross sectional study of 1756 children who were invited to participate in a comprehensive non-invasive eye exam. Uncorrected monocular VA with crowded tumbling E with a comprehensive ophthalmological examination were assessed. Testability rates of the whole population and VA of the healthy children for different age subgroups, gender, school type and the order of testing in which the ophthalmological examination was performed were evaluated. RESULTS: The overall testability rate was 95% (92% and 98% for children aged 3 and 4 years, respectively). The mean VA of the first-day assessment (first-VA) and best-VA over 2 days' assessments was 0.14 logMAR (95% CI 0.14 to 0.15) (decimal=0.72, 95% CI 0.71 to 0.73) and 0.13 logMAR (95% CI 0.13 to 0.14) (decimal=0.74, 95% CI 0.73 to 0.74). Analysis with age showed differences between groups in first-VA (F(3,1146)=10.0; p<0.001; eta2=0.026) and best-VA (F(3,1155)=8.8; p<0.001; eta2=0.022). Our normative was very highly correlated with previous reported HOTV Amblyopia-Treatment-Study (HOTV-ATS) (first-VA, r=0.97; best-VA, r=0.99), with 0.8 to 0.7 lines consistent overestimation for HOTV-ATS as described in literature. Overall false-positive referral was 1.3%, being specially low regarding anisometropias of >=2 logMAR lines (0.17%). Interocular difference >=1 line VA logMAR was not associated with age (p=0.195). CONCLUSIONS: This is the first normative for European Caucasian children with single crowded tumbling E in healthy eyes and the largest study comparing 3 and 4 years old testability. Testability rates are higher than found in literature with other optotypes, especially in children aged 3 years, where we found 5%-11% better testability rates. PMID- 28988162 TI - Organised screening for cervical cancer in France: a cost-effectiveness assessment. AB - OBJECTIVE: According to the third cancer plan, organised screening (OS) of cervical cancer (CC) among women aged 25-65 years should be implemented in France in the forthcoming years. The most efficient way to implement OS in the French healthcare system is yet to be determined. METHODS: A microsimulation model was developed adopting a collective 'all payers' perspective. A closed cohort of women eligible for CC screening and representative in terms of age and participation in individual screening (IndScr) by annual Papanicolaou (Pap) testing every 3 years was modelled on a lifetime horizon. Different OS strategies, additive to IndScr with a 61.9% participation rate based on mailed invitations to non-participant women to perform OS were assessed. Similar modalities were applied to OS and IndScr participants. Strategies implied different screening tests (Papanicolaou (Pap) test, human papillomavirus (HPV) test and p16/Ki67 double staining) and OS periodicity. RESULTS: Compared with IndScr only, all OS strategies were associated with decreased cancer incidence/mortality (from 14.2%/13.5% to 22.9%/25.8%). Most strategies generated extra costs ranging from ?37.9 to ?1607 per eligible woman. HPV testing every 10 and 5 years were cost saving. HPV tests every 10 and 5 years were the most efficient strategies, generating more survival at lower costs than Pap-based strategies. Compared to IndScr only, an HPV test every 10 years was cost saving. The most effective strategies were p16/Ki67 as primary or HPV positive confirmation tests, with respective incremental cost-effectiveness ratios of ?6 541 250 and ?101 391 per life year. Pap-based strategies generated intermediary results. CONCLUSION: OS strategies based on the HPV test appear highly efficient. However, our results rely on the assumption that women and practitioners comply with the recommended OS periodicities (3, 5, 10 years). Implementing these OS modalities will require major adaptations to the current CC screening organisation. Pap test-based strategies might be simpler to setup while preparing an appropriate implementation of more efficient OS screening modalities. PMID- 28988160 TI - Effect of MRI on preterm infants and their families: a randomised trial with nested diagnostic and economic evaluation. AB - BACKGROUND: We tested the hypothesis that routine MRI would improve the care and well-being of preterm infants and their families. DESIGN: Parallel-group randomised trial (1.1 allocation; intention-to-treat) with nested diagnostic and cost evaluations (EudraCT 2009-011602-42). SETTING: Participants from 14 London hospitals, imaged at a single centre. PATIENTS: 511 infants born before 33 weeks gestation underwent both MRI and ultrasound around term. 255 were randomly allocated (siblings together) to receive only MRI results and 255 only ultrasound from a paediatrician unaware of unallocated results; one withdrew before allocation. MAIN OUTCOME MEASURES: Maternal anxiety, measured by the State-Trait Anxiety inventory (STAI) assessed in 206/214 mothers receiving MRI and 217/220 receiving ultrasound. Secondary outcomes included: prediction of neurodevelopment, health-related costs and quality of life. RESULTS: After MRI, STAI fell from 36.81 (95% CI 35.18 to 38.44) to 32.77 (95% CI 31.54 to 34.01), 31.87 (95% CI 30.63 to 33.12) and 31.82 (95% CI 30.65 to 33.00) at 14 days, 12 and 20 months, respectively. STAI fell less after ultrasound: from 37.59 (95% CI 36.00 to 39.18) to 33.97 (95% CI 32.78 to 35.17), 33.43 (95% CI 32.22 to 34.63) and 33.63 (95% CI 32.49 to 34.77), p=0.02. There were no differences in health related quality of life. MRI predicted moderate or severe functional motor impairment at 20 months slightly better than ultrasound (area under the receiver operator characteristic curve (CI) 0.74; 0.66 to 0.83 vs 0.64; 0.56 to 0.72, p=0.01) but cost L315 (CI L295-L336) more per infant. CONCLUSIONS: MRI increased costs and provided only modest benefits. TRIAL REGISTRATION: ClinicalTrials.gov NCT01049594 https://clinicaltrials.gov/ct2/show/NCT01049594. EudraCT: EudraCT: 2009-011602-42 (https://www.clinicaltrialsregister.eu/). PMID- 28988163 TI - High-sensitivity C reactive protein as a predictor of inhospital mortality in patients with cardiovascular disease at an emergency department: a retrospective cohort study. AB - OBJECTIVE: We investigated whether serum high-sensitivity C reactive protein (hs CRP) levels measured in an emergency department (ED) are associated with inhospital mortality in patients with cardiovascular disease (CVD). DESIGN: A retrospective cohort study. SETTING: ED of a teaching hospital in Japan. PARTICIPANTS: 12 211 patients with CVD aged >=18 years who presented to the ED by an ambulance between 1 February 2006 and 30 September 2014 were evaluated. MAIN OUTCOME MEASURES: Inhospital mortality. RESULTS: 1156 patients had died. The inhospital mortality increased significantly with the hs-CRP levels (<3.0 mg/L: 7.0%, 95% CI 6.4 to 7.6; 3.1-5.4 mg/L: 9.6%, 95% CI 7.9 to 11.3: 5.5-11.5 mg/L: 11.2%, 95% CI 9.4 to 13.0; 11.6-33.2 mg/L: 12.3%, 95% CI 10.5 to 14.1 and >=33.3 mg/L: 19.9%, 95% CI 17.6 to 22.2). The age-adjusted and sex-adjusted HR for total mortality was increased significantly in the three >=5.5 mg/L groups compared with the <3.0 mg/L group (5.5-11.5 mg/L: HR=1.32, 95% CI 1.09 to 1.60, p=0.005; 11.6-33.2 mg/L: HR=1.38, 95% CI 1.14 to 1.65, p=0.001 and >=33.3 mg/L: HR=2.15, 95% CI 1.84 to 2.51, p<0.001). Similar findings were observed for the CVD subtypes of acute myocardial infarction, heart failure, cerebral infarction and intracerebral haemorrhage. This association remained unchanged even after adjustment for age, sex and white cell count and withstood Bonferroni adjustment for multiple testing. When the causes of death were divided into primary CVD and non-CVD deaths, the association between initial hs-CRP levels and mortality remained significant, but the influence of hs-CRP levels was greater in non-CVD deaths than CVD deaths. The percentage of non-CVD deaths increased with hs-CRP levels; among the patients with hs-CRP levels >=33.3 mg/L, non-CVD deaths accounted for 37.5% of total deaths. CONCLUSION: Our findings suggest that increased hs-CRP is a significant risk factor for inhospital mortality among patients with CVD in an ED. Particular attention should be given to our finding that non-CVD death is a major cause of death among patients with CVD with higher hs-CRP levels. PMID- 28988164 TI - Infant BMI peak as a predictor of overweight and obesity at age 2 years in a Chinese community-based cohort. AB - OBJECTIVES: Infant body mass index (BMI) peak has proven to be a useful indicator for predicting childhood obesity risk in American and European populations. However, it has not been assessed in China. We characterised infant BMI trajectories in a Chinese longitudinal cohort and evaluated whether BMI peak can predict overweight and obesity at age 2 years. METHODS: Serial measurements (n=6 12) of weight and length were taken from healthy term infants (n=2073) in a birth cohort established in urban Shanghai. Measurements were used to estimate BMI growth curves from birth to 13.5 months using a polynomial regression model. BMI peak characteristics, including age (in months) and magnitude (BMI, in kg/m2) at peak and prepeak velocities (in kg/m2/month), were estimated. The relationship between infant BMI peak and childhood BMI at age 2 years was examined using binary logistic analysis. RESULTS: Mean age at peak BMI was 7.61 months, with a magnitude of 18.33 kg/m2. Boys (n=1022) had a higher average peak BMI (18.60 vs 18.07 kg/m2, p<0.001) and earlier average achievement of peak value (7.54 vs 7.67 months, p<0.05) than girls (n=1051). With 1 kg/m2 increase in peak BMI and 1 month increase in peak time, the risk of overweight at age 2 years increased by 2.11 times (OR 3.11; 95% CI 2.64 to 3.66) and 35% (OR 1.35; 95% CI 1.21 to 1.50), respectively. Similarly, higher BMI magnitude (OR 2.69; 95% CI 2.00 to 3.61) and later timing of infant BMI peak (OR 1.35; 95% CI 1.08 to 1.68) were associated with an increased risk of childhood obesity at age 2 years. CONCLUSIONS: We have shown that infant BMI peak is valuable for predicting early childhood overweight and obesity in urban Shanghai. Because this is the first Chinese community-based cohort study of this nature, future research is required to examine infant populations in other areas of China. PMID- 28988165 TI - Documenting and explaining the HIV decline in east Zimbabwe: the Manicaland General Population Cohort. AB - PURPOSE: The Manicaland cohort was established to provide robust scientific data on HIV prevalence and incidence, patterns of sexual risk behaviour and the demographic impact of HIV in a sub-Saharan African population subject to a generalised HIV epidemic. The aims were later broadened to include provision of data on the coverage and effectiveness of national HIV control programmes including antiretroviral therapy (ART). PARTICIPANTS: General population open cohort located in 12 sites in Manicaland, east Zimbabwe, representing 4 major socioeconomic strata (small towns, agricultural estates, roadside settlements and subsistence farming areas). 9,109 of 11,453 (79.5%) eligible adults (men 17-54 years; women 15-44 years) were recruited in a phased household census between July 1998 and January 2000. Five rounds of follow-up of the prospective household census and the open cohort were conducted at 2-year or 3-year intervals between July 2001 and November 2013. Follow-up rates among surviving residents ranged between 77.0% (over 3 years) and 96.4% (2 years). FINDINGS TO DATE: HIV prevalence was 25.1% at baseline and had a substantial demographic impact with 10 fold higher mortality in HIV-infected adults than in uninfected adults and a reduction in the growth rate in the worst affected areas (towns) from 2.9% to 1.0%pa. HIV infection rates have been highest in young adults with earlier commencement of sexual activity and in those with older sexual partners and larger numbers of lifetime partners. HIV prevalence has since fallen to 15.8% and HIV incidence has also declined from 2.1% (1998-2003) to 0.63% (2009-2013) largely due to reduced sexual risk behaviour. HIV-associated mortality fell substantially after 2009 with increased availability of ART. FUTURE PLANS: We plan to extend the cohort to measure the effects on the epidemic of current and future HIV prevention and treatment programmes. Proposals for access to these data and for collaboration are welcome. PMID- 28988166 TI - Loneliness and depression among rural empty-nest elderly adults in Liuyang, China: a cross-sectional study. AB - OBJECTIVE: To compare loneliness, depressive symptoms and major depressive episodes between empty-nest and not-empty-nest older adults in rural areas of Liuyang city, Hunan, China. METHODS: A cross-sectional multi-stage random cluster survey was conducted from November 2011 to April 2012 in Liuyang, China. A total of 839 rural older residents aged 60 or above completed the survey (response rate 97.6%). In line with the definition of empty nest, 25 participants who had no children were excluded from the study, while the remaining 814 elderly adults with at least one child were included for analysis. Loneliness and depressive symptoms in rural elderly parents were assessed using the short-form UCLA Loneliness Scale (ULS-6) and the Geriatric Depression Scale (GDS). Major depressive episodes were diagnosed using the Structured Clinical Interview for DSM-IV (SCID-I). RESULTS: Significant differences were found between empty-nest and not-empty-nest older adults regarding loneliness (16.19+/-3.90 vs. 12.87+/ 3.02, Cohen's d=0.97), depressive symptoms (8.50+/-6.26 vs. 6.92+/-5.19, Cohen's d=0.28) and the prevalence of major depressive episodes (10.1% vs. 4.6%) (all p<0.05). After controlling for demographic characteristics and physical disease, the differences in loneliness, depressive symptoms and major depressive episodes remained significant. Path analysis showed that loneliness mediated the relationship between empty-nest syndrome and depressive symptoms and major depressive episodes. CONCLUSION: Loneliness and depression are more severe among empty-nest than not-empty-nest rural elderly adults. Loneliness was a mediating variable between empty-nest syndrome and depression. PMID- 28988167 TI - Financial incentives to discontinue long-term benzodiazepine use: a discrete choice experiment investigating patient preferences and willingness to participate. AB - OBJECTIVES: Investigate the acceptability of financial incentives for initiating a medically supervised benzodiazepine discontinuation programme among people with long-term benzodiazepine use and to identify programme features that influence willingness to participate. METHODS: We conducted a discrete choice experiment in which we presented a variety of incentive-based programs to a sample of older adults with long-term benzodiazepine use identified using the outpatient electronic health record of a university-owned health system. We studied four programme variables: incentive amount for initiating the programme, incentive amount for successful benzodiazepine discontinuation, lottery versus certain payment and whether partial payment was given for dose reduction. Respondents reported their willingness to participate in the programmes and additional information was collected on demographics, history of use and anxiety symptoms. RESULTS: The overall response rate was 28.4%. Among the 126 respondents, all four programme variables influenced stated preferences. Respondents strongly preferred guaranteed cash-based incentives as opposed to a lottery, and the dollar amount of both the starting and conditional incentives had a substantial impact on choice. Willingness to participate increased with the amount of conditional incentive. Programme participation also varied by gender, duration of use and income. CONCLUSIONS: Participation in an incentive-based benzodiazepine discontinuation programme might be relatively low, but is modifiable by programme variables including incentive amounts. These results will be helpful to inform the design of future trials of benzodiazepine discontinuation programmes. Further research is needed to assess the financial viability and potential cost effectiveness of such economic incentives. PMID- 28988168 TI - How information about overdetection changes breast cancer screening decisions: a mediation analysis within a randomised controlled trial. AB - OBJECTIVES: In a randomised controlled trial, we found that informing women about overdetection changed their breast screening decisions. We now present a mediation analysis exploring the psychological pathways through which study participants who received the intervention processed information about overdetection and how this influenced their decision-making. We examined a series of potential mediators in the causal chain between exposure to overdetection information and women's subsequently reported breast screening intentions. DESIGN: Serial multiple mediation analysis within a randomised controlled trial. SETTING: New South Wales, Australia. PARTICIPANTS: 811 women aged 48-50 years with no personal history of breast cancer. INTERVENTIONS: Two versions of a decision aid giving women information about breast cancer deaths averted and false positives from mammography screening, either with (intervention) or without (control) information on overdetection. MAIN OUTCOME: Intentions to undergo breast cancer screening in the next 2-3 years. MEDIATORS: Knowledge about overdetection, worry about breast cancer, attitudes towards breast screening and anticipated regret. RESULTS: The effect of information about overdetection on women's breast screening intentions was mediated through multiple cognitive and affective processes. In particular, the information led to substantial improvements in women's understanding of overdetection, and it influenced-both directly and indirectly via its effect on knowledge-their attitudes towards having screening. Mediation analysis showed that the mechanisms involving knowledge and attitudes were particularly important in determining women's intentions about screening participation. CONCLUSIONS: Even in this emotive context, new information influenced women's decision-making by changing their understanding of possible consequences of screening and their attitudes towards undergoing it. These findings emphasise the need to provide good-quality information on screening outcomes and to communicate this information effectively, so that women can make well-informed decisions. TRIAL REGISTRATION NUMBER: This study was prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12613001035718) on 17 September 2013. PMID- 28988169 TI - Predicting the hand, foot, and mouth disease incidence using search engine query data and climate variables: an ecological study in Guangdong, China. AB - OBJECTIVES: Hand, foot, and mouth disease (HFMD) has caused a substantial burden in China, especially in Guangdong Province. Based on the enhanced surveillance system, we aimed to explore whether the addition of temperate and search engine query data improves the risk prediction of HFMD. DESIGN: Ecological study. SETTING AND PARTICIPANTS: Information on the confirmed cases of HFMD, climate parameters and search engine query logs was collected. A total of 1.36 million HFMD cases were identified from the surveillance system during 2011-2014. Analyses were conducted at aggregate level and no confidential information was involved. OUTCOME MEASURES: A seasonal autoregressive integrated moving average (ARIMA) model with external variables (ARIMAX) was used to predict the HFMD incidence from 2011 to 2014, taking into account temperature and search engine query data (Baidu Index, BDI). Statistics of goodness-of-fit and precision of prediction were used to compare models (1) based on surveillance data only, and with the addition of (2) temperature, (3) BDI, and (4) both temperature and BDI. RESULTS: A high correlation between HFMD incidence and BDI (r=0.794, p<0.001) or temperature (r=0.657, p<0.001) was observed using both time series plot and correlation matrix. A linear effect of BDI (without lag) and non-linear effect of temperature (1 week lag) on HFMD incidence were found in a distributed lag non linear model. Compared with the model based on surveillance data only, the ARIMAX model including BDI reached the best goodness-of-fit with an Akaike information criterion (AIC) value of -345.332, whereas the model including both BDI and temperature had the most accurate prediction in terms of the mean absolute percentage error (MAPE) of 101.745%. CONCLUSIONS: An ARIMAX model incorporating search engine query data significantly improved the prediction of HFMD. Further studies are warranted to examine whether including search engine query data also improves the prediction of other infectious diseases in other settings. PMID- 28988170 TI - Effectiveness of the HuCare Quality Improvement Strategy on health-related quality of life in patients with cancer: study protocol of a stepped-wedge cluster randomised controlled trial (HuCare2 study). AB - INTRODUCTION: Our group previously demonstrated the feasibility of the HuCare Quality Improvement Strategy (HQIS), aimed at integrating into practice six psychosocial interventions recommended by international guidelines. This trial will assess whether the introduction of the strategy in oncology wards improves patient's health-related quality of life (HRQoL). METHODS AND ANALYSIS: Multicentre, incomplete stepped-wedge cluster randomised controlled trial, conducted in three clusters of five centres each, in three equally spaced time epochs. The study also includes an initial epoch when none of the centres are exposed to the intervention, and a final epoch when all centres will have implemented the strategy. The intervention is applied at a cluster level, and assessed at an individual level with cross-sectional model. A total of 720 patients who received a cancer diagnosis in the previous 2 months and about to start medical treatment will be enrolled. The primary aim is to evaluate the effectiveness of the HQIS versus standard care in terms of improvement of at least one of two domains (emotional and social functions) of HRQoL using the EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 items) questionnaire, at baseline and at 3 months. This outcome was chosen because patients with cancer generally exhibit low HRQoL, particularly at certain stages of care, and because it allows to assess the strategy's impact as perceived by patients themselves. The HQIS comprises three phases: (1) clinician training-to improve communication-relational skills and instruct on the project; (2) centre support-four on-site visits by experts of the project team, aimed to boost motivation, help with context analysis and identification of solutions; (3) implementation of Evidence-Based Medicine (EBM) recommendations at the centre. ETHICS AND DISSEMINATION: Ethics committee review approval has been obtained from the Ethics Committee of Parma. Results will be disseminated at conferences, and in peer-reviewed and professional journals intended for policymakers and managers. TRIAL REGISTRATION NUMBER: NCT03008993; Pre-results. PMID- 28988171 TI - Post-trauma coping in the context of significant adversity: a qualitative study of young people living in an urban township in South Africa. AB - OBJECTIVE: Compared with knowledge of the post-trauma needs of young people living in developed countries, little is known about the needs of those in low middle-income countries. Such information is crucial, particularly as young people in these environments can be at increased risk of experiencing trauma, coupled with less available resources for formal support. The aim of this study was to explore post-trauma coping and support-seeking of young people living in a high-adversity settlement in South Africa. DESIGN: Semistructured qualitative interviews analysed using thematic analysis. SETTING: An urban settlement ('township') in Cape Town, South Africa. PARTICIPANTS: 25 young people, aged 13 17 years, who had experienced trauma. Events included serious car accidents, hearing of a friend's violent death, and rape, and all reported having experienced multiple traumatic events. All participants identified as black South African and spoke Xhosa as their first language. RESULTS: Social support was considered key to coping after trauma, although the focus of the support differed depending on the source. Parents would most commonly provide practical support, particularly around safety. Peers often provided an avenue to discuss the event and young person's emotional well-being more openly. Outside of social support another key theme was that there were numerous community-level barriers to participants receiving support following trauma. Many young people continued to be exposed to the perpetrator of the event, while there was also the realistic concern around future traumas and safety, community stigma and a perceived lack of justice. CONCLUSION: This study provides insight into how young people cope and seek support following trauma when they are living in a context of significant adversity and risk. Overall, most young people identified helpful sources of support and thought talking about the event was a useful strategy, but concerns around safety and trust could impede this process. PMID- 28988172 TI - Haemodynamic response to crystalloids or colloids in shock: an exploratory subgroup analysis of a randomised controlled trial. AB - OBJECTIVE: To compare the haemodynamic effect of crystalloids and colloids during acute severe hypovolaemic shock. DESIGN: Exploratory subgroup analysis of a multicentre randomised controlled trial (Colloids Versus Crystalloids for the Resuscitation of the Critically Ill, CRISTAL, ClinicalTrials.gov NCT00318942). SETTING: CRISTAL was conducted in intensive care units in Europe, North Africa and Canada. PARTICIPANTS: Current analysis included all patients who had a pulmonary artery catheter in place at randomisation. 220 patients (117 received crystalloids vs 103 colloids) underwent pulmonary artery catheterisation. INTERVENTION: Crystalloids versus colloids for fluid resuscitation in hypovolaemic shock. OUTCOME MEASURES: Haemodynamic data were collected at the time of randomisation and subsequently on days 1, 2, 3, 4, 5, 6 and 7. RESULTS: Median cumulative volume of fluid administered during the first 7 days was higher in the crystalloids group than in the colloids group (3500 (2000-6000) vs 2500 (1000-4000) mL, p=0.01). Patients in the colloids arm exhibited a lower heart rate over time compared with those allocated to the crystalloids arm (p=0.014). There was no significant difference in Cardiac Index (p=0.053), mean blood pressure (p=0.4), arterial lactates (p=0.9) or global Sequential Organ Failure Assessment score (p=0.3) over time between arms. CONCLUSIONS: During acute severe hypovolaemic shock, patients monitored by a pulmonary artery catheter achieved broadly similar haemodynamic outcomes, using lower volumes of colloids than crystalloids. The heart rate was lower in the colloids arm. PMID- 28988173 TI - Protocol for the TIDAL Melanoma Study: topical imiquimod or diphenylcyclopropenone for the management of cutaneous in-transit melanoma metastases-a phase II, single centre, randomised, pilot study. AB - INTRODUCTION: Patients with in-transit melanoma metastases present a therapeutic challenge. Complete surgical excision of localised disease is considered as the gold standard; however, surgery is not always acceptable and alternatives are required. Treatment results reported using imiquimod and diphenylcyclopropenone (DPCP) suggest that topical immunotherapies can be used to successfully treat select patients with melanoma metastases. A phase II, randomised, single centre, pilot study was designed to assess the clinical efficacy and safety of DPCP and imiquimod for the treatment of superficial, cutaneous in-transit melanoma metastases. METHODS AND ANALYSIS: This is an open-label, non-superiority, pilot study with no treatment cross-over. Eligible patients are randomised in a 1:1 ratio to receive topical therapy for up to 12 months with a minimum follow-up period of 12 months. The target sample size is 30 patients, with 15 allocated to each treatment arm. The primary endpoint is the number of patients experiencing a complete response of treated lesions as determined clinically using Response Evaluation Criteria in Solid Tumours. This trial incorporates health-related quality of life measures and biological tissue collection for further experimental substudies. The study will also facilitate a health economic analysis. ETHICS AND DISSEMINATION: Approval was obtained from the Human Research Ethics Committee at the participating centre, and recruitment has commenced. The results of this study will be submitted for formal publication within a peer reviewed journal. TRIAL REGISTRATION NUMBER: Prospectively registered on 16 October 2015 with the Australian New Zealand Clinical Trials Registry (ACTRN12615001088538). This study conforms to WHO Trial Registration Data Set. PMID- 28988174 TI - The prognostic significance of smoking cessation after acute coronary syndromes: an observational, multicentre study from the Melbourne interventional group registry. AB - OBJECTIVE: We aim to ascertain the prognostic significance of persistent smoking and smoking cessation after an acute coronary syndrome (ACS) in the era of percutaneous coronary intervention (PCI) and optimal secondary prevention pharmacotherapy. METHODS: Consecutive patients from the Melbourne Interventional Group registry (2005-2013) who were alive at 30 days post-ACS presentation were included in our observational cohort study. Patients were divided into four categories based on their smoking status: non-smoker; ex-smoker (quit >1 month before ACS); recent quitter (smoker at presentation but quit by 30 days) and persistent smoker (smoker at presentation and at 30 days). The primary endpoint was survival ascertained through the Australian National Death Index linkage. A Cox-proportional hazards model was used to estimate the adjusted HR and 95% CI for survival. RESULTS: Of the 9375 patients included, 2728 (29.1%) never smoked, 3712 (39.6%) were ex-smokers, 1612 (17.2%) were recent quitters and 1323 (14.1%) were persistent smokers. Cox-proportional hazard modelling revealed, compared with those who had never smoked, that persistent smoking (HR 1.78, 95% CI 1.36 to 2.32, p<0.001) was an independent predictor of increased hazard (mean follow-up 3.9+/-2.2 years) while being a recent quitter (HR 1.27, 95% CI 0.96 to 1.68, p=0.10) or an ex-smoker (HR 1.03, 95% CI 0.87 to 1.22, p=0.72) were not. CONCLUSIONS: In a contemporary cohort of patients with ACS, those who continued to smoke had an 80% risk of lower survival while those who quit had comparable survival to lifelong non-smokers. This underscores the importance of smoking cessation in secondary prevention despite the improvement in management of ACS with PCI and pharmacotherapy. PMID- 28988175 TI - Assessment of the effects of decision aids about breast cancer screening: a systematic review and meta-analysis. AB - OBJECTIVE: The aim of this systematic review and meta-analysis of randomised controlled trials (RCTs) and observational studies is to assess the effect of decision aids (DAs) in women aged 50 and below facing the decision to be screened for breast cancer. SETTING: Screening for breast cancer. INTERVENTION: DAs aimed to help women make a deliberative choice regarding participation in mammography screening by providing information on the options and outcomes. ELIGIBLE STUDIES: We included published original, non-pilot, studies that assess the effect of DAs for breast cancer screening. We excluded the studies that evaluated only participation intention or actual uptake. The studies' risk of bias was assessed with the Cochrane Collaboration's tool for RCTs and the National Institutes of Health Quality Assessment Tool for non-RCTs. PRIMARY AND SECONDARY OUTCOMES: The main outcome measures were informed choice, decisional conflict and/or confidence, and knowledge. Secondary outcomes were values, attitudes, uncertainty and intention to be screened. RESULTS: A total of 607 studies were identified, but only 3 RCTs and 1 before-after study were selected. The use of DAs increased the proportion of women making an informed decision by 14%, 95% CI (2% to 27%) and the proportion of women with adequate knowledge by 12%, 95% CI (7% to 16%). We observed heterogeneity among the studies in confidence in the decision. The meta-analysis of the RCTs showed a significant decrease in confidence in the decision and in intention to be screened. CONCLUSIONS: Tools to aid decision making in screening for breast cancer improve knowledge and promote informed decision; however, we found divergent results on decisional conflict and confidence in the decision. Under the current paradigm change, which favours informed choice rather than maximising uptake, more research is necessary for the improvement of DAs. PMID- 28988176 TI - Implementing communication and decision-making interventions directed at goals of care: a theory-led scoping review. AB - OBJECTIVES: To identify the factors that promote and inhibit the implementation of interventions that improve communication and decision-making directed at goals of care in the event of acute clinical deterioration. DESIGN AND METHODS: A scoping review was undertaken based on the methodological framework of Arksey and O'Malley for conducting this type of review. Searches were carried out in Medline and Cumulative Index to Nursing and Allied Health Literature (CINAHL) to identify peer-reviewed papers and in Google to identify grey literature. Searches were limited to those published in the English language from 2000 onwards. Inclusion and exclusion criteria were applied, and only papers that had a specific focus on implementation in practice were selected. Data extracted were treated as qualitative and subjected to directed content analysis. A theory-informed coding framework using Normalisation Process Theory (NPT) was applied to characterise and explain implementation processes. RESULTS: Searches identified 2619 citations, 43 of which met the inclusion criteria. Analysis generated six themes fundamental to successful implementation of goals of care interventions: (1) input into development; (2) key clinical proponents; (3) training and education; (4) intervention workability and functionality; (5) setting and context; and (6) perceived value and appraisal. CONCLUSIONS: A broad and diverse literature focusing on implementation of goals of care interventions was identified. Our review recognised these interventions as both complex and contentious in nature, making their incorporation into routine clinical practice dependent on a number of factors. Implementing such interventions presents challenges at individual, organisational and systems levels, which make them difficult to introduce and embed. We have identified a series of factors that influence successful implementation and our analysis has distilled key learning points, conceptualised as a set of propositions, we consider relevant to implementing other complex and contentious interventions. PMID- 28988177 TI - Fabry disease due to D313Y and novel GLA mutations. AB - OBJECTIVES: Our aim is to report four novel alpha-gal A gene (GLA) mutations resulting in Fabry disease (FD) and provide evidence of pathogenicity of the D313Y mutation regarding which contradictory data have been presented in the literature. SETTING AND PARTICIPANTS: Twenty-five family members of nine unrelated patients with definite FD diagnosis, 10 clinically suspected cases and 18 members of their families were included in this polycentric cohort study. PRIMARY AND SECONDARY OUTCOME MEASURES: Genotyping and measurement of lyso-Gb3 was performed in all individuals. The alpha-Gal A activity was measured in all men as well as plasma and urine Gb3 concentration in selected cases. Optical and electron microscopy was performed in kidney biopsies of selected patients. All the above were evaluated in parallel with the clinical data of the patients. RESULTS: Fourteen new cases of FD were recognised, four of which were carrying already described GLA mutations. Four novel GLA mutations, namely c.835C>T, c.280T>A, c.924A>C and c.511G>A, resulting in a classic FD phenotype were identified. Moreover, FD was definitely diagnosed in five patients carrying the D313Y mutation. Eight D313Y carriers were presenting signs of FD despite not fulfilling the criteria of the disease, two had no FD signs and two others were apparently healthy. CONCLUSIONS: Four novel GLA pathogenic mutations are reported and evidence of pathogenicity of the D313Y mutation is provided. It seems that the D313Y mutation is related to a later-onset milder phenotype than the typical phenotype with normal lysoGb3 concentration. Our study underlines the significance of family member genotyping and newborn screening to avoid misdiagnoses and crucial delays in diagnosis and treatment of the disease. PMID- 28988178 TI - Effect of socio-demographic factors on the association between multimorbidity and healthcare costs: a population-based, retrospective cohort study. AB - OBJECTIVES: To estimate the attributable costs of multimorbidity and assess whether the association between the level of multimorbidity and health system costs varies by socio-demographic factors in young (<65 years) and older (>=65 years) adults living in Ontario, Canada. DESIGN: A population-based, retrospective cohort study SETTING: The province of Ontario, Canada PARTICIPANTS: 6 639 089 Ontarians who were diagnosed with at least one of 16 selected medical conditions on 1 April 2009. MAIN OUTCOME MEASURES: From the perspective of the publicly funded healthcare system, total annual healthcare costs were derived from linked provincial health administrative databases using a person-level costing method. We used generalised linear models to examine the association between the level of multimorbidity and healthcare costs and the extent to which socio-demographic variables modified this association. RESULTS: Attributable total costs of multimorbidity ranged from C$377 to C$2073 for young individuals and C$1026 to C$3831 for older adults. The association between the degree of multimorbidity and healthcare costs was significantly modified by age (p<0.001), sex (p<0.001) and neighbourhood income (p<0.001) in both age groups, and the positive association between healthcare costs and levels of multimorbidity was statistically stronger for older than younger adults. For individuals aged 65 years or younger, the increase in healthcare costs was more gradual in women than in their male counterparts, however, for those aged 65 years or older, the increase in healthcare costs was significantly greater among women than men. Lastly, we also observed that the positive association between the level of multimorbidity and healthcare costs was significantly greater at higher levels of marginalisation. CONCLUSION: Socio-demographic factors are important effect modifiers of the relationship between multimorbidity and healthcare costs and should therefore be considered in any discussion of the implementation of healthcare policies and the organisation of healthcare services aimed at controlling healthcare costs associated with multimorbidity. PMID- 28988179 TI - Associations of perceived interparental relationship, family harmony and family happiness with smoking intention in never-smoking Chinese children and adolescents: a cross-sectional study. AB - OBJECTIVE: To examine the associations of perceived interparental relationship, family harmony and family happiness with smoking intention in never-smoking Chinese children and adolescents in Hong Kong. DESIGN, SETTINGS AND PARTICIPANTS: Cross-sectional surveys of 15 753 primary (grades 4-6) and 38 398 secondary (grades 7-12) never-smoking students from 71 to 75 randomly selected primary and secondary schools in Hong Kong, 2012-2013. MEASUREMENTS: Outcome variable was smoking intention which denoted any affirmative response to smoke within the coming year or when a cigarette was offered by a good friend. Exposure variables were perceived interparental relationship and family harmony each measured on a five-point scale from 'very good' to 'very bad' and perceived family happiness on a four-point scale from 'very happy' to 'not happy at all'. Potential confounders included age, sex, family structure, perceived family affluence, parental smoking and sibling smoking. RESULTS: In primary students, the adjusted ORs (AORs) (95% CI) of smoking intention generally increased with more negative perception of the family relationship: up to 3.67 (1.91 to 7.05) for interparental relationship, 7.71 (4.38 to 13.6) for family harmony and 5.40 (3.41 to 8.55) for family happiness. For secondary students, the corresponding AORs (95% CI) were 2.15 (1.64 to 2.82) for interparental relationship, 2.98 (2.31 to 3.84) for family harmony and 2.61 (1.80 to 3.79) for family happiness. All p for trend <0.001. CONCLUSIONS: More negatively perceived interparental relationship, family harmony and family happiness were associated with higher odds of smoking intention with dose-response relationships in never-smoking Chinese children and adolescents in Hong Kong. Children's perception of their family relationship may be an important intervening point for preventing youth from initiating smoking. PMID- 28988180 TI - Are there any differences between different testing sites? A cross-sectional study of a Norwegian low-threshold HIV testing service for men who have sex with men. AB - OBJECTIVE: To describe a Norwegian low-threshold HIV testing service targeting men who have sex with men (MSM). DESIGN AND SETTING: After the HIV testing consultation, all users of the HIV testing service were invited to answer the study questionnaire. The study setting included the sites where testing was performed, that is, the testing service's office in Oslo, cruising areas, bars/clubs and in hotels in other Norwegian cities. PARTICIPANTS: MSM users of the testing service. PRIMARY AND SECONDARY OUTCOME MEASURES: Data were collected on demographics, HIV testing and sexual behaviour as well as the participant's motivations for choosing to take an HIV test at this low-threshold HIV testing service. The data are stratified by testing site. RESULTS: 1577 HIV testing consultations were performed, the study sample consisted of 732 MSM users. 11 tested positive for HIV. 21.7% had a non-western background, 27.1% reported having a non-gay sexual orientation. 21.9% had 10 or more male sexual partners during the last year, 27.9% reported also having had a female sexual partner. 56.4% reported having practised unprotected anal intercourse during the last 6 months. 20.1% had never tested for HIV before. Most of these user characteristics varied by testing sites. CONCLUSIONS: The Norwegian low-threshold testing service recruits target groups that are otherwise hard to reach with HIV testing. This may indicate that the testing service contributes to increase HIV testing rates among MSM in Norway. PMID- 28988181 TI - Search for unpublished data by systematic reviewers: an audit. AB - OBJECTIVES: We audited a selection of systematic reviews published in 2013 and reported on the proportion of reviews that researched for unpublished data, included unpublished data in analysis and assessed for publication bias. DESIGN: Audit of systematic reviews. DATA SOURCES: We searched PubMed and Ovid MEDLINE In Process & Other Non-Indexed Citations between 1 January 2013 and 31 December 2013 for the following journals: Journal of the American Medical Association, The British Medical Journal, Lancet, Annals of Internal Medicine and the Cochrane Database of Systematic Reviews. We also searched the Cochrane Library and included 100 randomly selected Cochrane reviews. ELIGIBILITY CRITERIA: Systematic reviews published in 2013 in the selected journals were included. Methodological reviews were excluded. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently reviewed each included systematic review. The following data were extracted: whether the review searched for grey literature or unpublished data, the sources searched, whether unpublished data were included in analysis, whether publication bias was assessed and whether there was evidence of publication bias. MAIN FINDINGS: 203 reviews were included for analysis. 36% (73/203) of studies did not describe any attempt to obtain unpublished studies or to search grey literature. 89% (116/130) of studies that sought unpublished data found them. 33% (68/203) of studies included an assessment of publication bias, and 40% (27/68) of these found evidence of publication bias. CONCLUSION: A significant fraction of systematic reviews included in our study did not search for unpublished data. Publication bias may be present in almost half the published systematic reviews that assessed for it. Exclusion of unpublished data may lead to biased estimates of efficacy or safety in systematic reviews. PMID- 28988182 TI - Secondhand tobacco smoke exposure and pulmonary function: a cross-sectional study among non-smoking employees of bar and restaurants in Santiago, Chile. AB - INTRODUCTION: The workplace remains a significant source of secondhand smoke (SHS) exposure. This pollutant is known to be associated with respiratory and cardiovascular problems, but its effects on specific pulmonary function parameters remain largely unexplored. The objectives of this study were to measure SHS exposure among non-smoking employees of bar and restaurants in Santiago, Chile and to evaluate the effects of such exposure on pulmonary function. METHODS: Cross-sectional design. The study sample included non-smoking workers from 57 restaurants and bars in Santiago, Chile. The outcome variable was pulmonary function and the exposure variables were urine cotinine concentration, a biomarker for current SHS exposure, and years of SHS exposure in the workplace as proxy of chronic exposure. Personal and occupational variables were also recorded. Data analysis was performed using linear regression models adjusted by confounders. RESULTS: The median age of the workers was 35 years and the median employment duration at the analysed venues was 1 year. Workers in smoking facilities reported greater SHS exposure (36 hours per week) than workers in smoke-free locations (4 hours per week). Urine cotinine levels were inversely correlated with forced vital capacity, but the finding was not statistically significant (beta=-0.0002; 95% CI -0.007 to 0.006). Years of exposure to SHS showed to be significantly associated with forced expiratory flow25/75 (beta= 0.006; 95% CI -0.010 to -0.0004). CONCLUSION: These findings suggest that cumulative exposure to SHS at work may contribute to deterioration of pulmonary function in non-smoking employees. PMID- 28988183 TI - Neurological outcome after minimal invasive coronary artery surgery (NOMICS): protocol for an observational prospective cohort study. AB - INTRODUCTION: Adverse neurocognitive outcomes are still an important cause of morbidity and mortality after cardiac surgery. The most common neurocognitive disorders after conventional cardiac surgery are postoperative cognitive dysfunction (POCD), stroke and delirium. Minimal invasive cardiac procedures have recently been introduced into practice. Endoscopic coronary artery bypass grafting (Endo-CABG) is a minimal invasive cardiac procedure based on the conventional CABG procedure. Neurocognitive outcome after minimal invasive cardiac surgery, including Endo-CABG, has never been studied. Therefore, the main objective of this study is to examine neurocognitive outcome after Endo-CABG. METHODS AND ANALYSIS: We will perform a prospective observational cohort study including 150 patients. Patients are categorised into three groups: (1) patients undergoing Endo-CABG, (2) patients undergoing a percutaneous coronary intervention and (3) a healthy volunteer group. All patients in the Endo-CABG group will be treated following a uniform, standardised protocol. To assess neurocognitive outcome after surgery, a battery of six neurocognitive tests will be administered at baseline and at 3-month follow-up. In the Endo-CABG group, a neurological examination will be performed at baseline and postoperatively and delirium will be scored at the intensive care unit. Quality of life (QOL), anxiety and depression will be assessed at baseline and at 3-month follow-up. Satisfaction with Endo-CABG will be assessed at 3-month follow-up. Primary endpoints are the incidence of POCD, stroke and delirium after Endo-CABG. Secondary endpoints are QOL after Endo-CABG, patient satisfaction with Endo-CABG and the incidence of anxiety and depression after Endo-CABG. ETHICS AND DISSEMINATION: The neurological outcome after minimal invasive coronary artery surgery study has received approval of the Jessa Hospital ethics board. It is estimated that the trial will be executed from December 2016 to January 2018, including enrolment and follow-up. Analysis of data, followed by publication of the results, is expected in 2018. TRIAL REGISTRATION NUMBER: NCT02979782. PMID- 28988184 TI - Influence of frailty in older patients undergoing emergency laparotomy: a UK based observational study. AB - INTRODUCTION: The National Emergency Laparotomy Audit (NELA) has reported that older patients (>=65 years) form a large percentage of emergency high-risk cases with increased postoperative morbidity and mortality. With the population continuing to age rapidly, it is clear that a greater understanding of the factors affecting surgical outcomes in older patients is required. Frailty is a relatively new concept taking into account a variety of factors that increase an individual's vulnerability to increased dependency and death. Research has suggested that high frailty scores increase postoperative complications, length of stay and mortality but the majority of these studies have been carried out on elective patients. Knowledge of how frailty affects patients in an emergency setting would aid clinicians' and patients' decision-making process. METHODS AND ANALYSIS: This multicentre study will include consecutive adult patients aged 65 years and over undergoing emergency laparotomies over a 3-month period at 52 National Health Service hospitals across the UK. The primary outcome will be 90 day mortality. Secondary outcomes will include length of hospital stay, 30-day complications, change in level of independence and 30-day readmission. This study has been powered to detect a 10% change in mortality associated with frailty (n=500 patients). ETHICS AND DISSEMINATION: This study has been approved by the National Health Service Research Ethics Committee. It has been registered centrally with HRA for English sites, NRSPCC for Scottish sites and Health and Care Research Permissions Service for sites in Wales.Dissemination will be via international and national surgical and geriatric conferences. In addition, manuscripts will be prepared following the close of the project. TRIAL REGISTRATION NUMBER: This study is also registered online at www.clinicaltrials.gov (registration number NCT02952430). PMID- 28988185 TI - Longer-term needs of stroke survivors with communication difficulties living in the community: a systematic review and thematic synthesis of qualitative studies. AB - OBJECTIVE: To review and synthesise qualitative literature relating to the longer term needs of community dwelling stroke survivors with communication difficulties including aphasia, dysarthria and apraxia of speech. DESIGN: Systematic review and thematic synthesis. METHOD: We included studies employing qualitative methodology which focused on the perceived or expressed needs, views or experiences of stroke survivors with communication difficulties in relation to the day-to-day management of their condition following hospital discharge. We searched MEDLINE, EMBASE, PsycINFO, CINAHL, The Cochrane Library, International Bibliography of the Social Sciences and AMED and undertook grey literature searches. Studies were assessed for methodological quality by two researchers independently and the findings were combined using thematic synthesis. RESULTS: Thirty-two studies were included in the thematic synthesis. The synthesis reveals the ongoing difficulties stroke survivors can experience in coming to terms with the loss of communication and in adapting to life with a communication difficulty. While some were able to adjust, others struggled to maintain their social networks and to participate in activities which were meaningful to them. The challenges experienced by stroke survivors with communication difficulties persisted for many years poststroke. Four themes relating to longer-term need were developed: managing communication outside of the home, creating a meaningful role, creating or maintaining a support network and taking control and actively moving forward with life. CONCLUSIONS: Understanding the experiences of stroke survivors with communication difficulties is vital for ensuring that longer-term care is designed according to their needs. Wider psychosocial factors must be considered in the rehabilitation of people with poststroke communication difficulties. Self-management interventions may be appropriate to help this subgroup of stroke survivors manage their condition in the longer-term; however, such approaches must be designed to help survivors to manage the unique psychosocial consequences of poststroke communication difficulties. PMID- 28988186 TI - How do general practitioners put preventive care recommendations into practice? A cross-sectional study in Switzerland and France. AB - OBJECTIVES: We previously identified that general practitioners (GPs) in French speaking regions of Europe had a variable uptake of common preventive recommendations. In this study, we describe GPs' reports of how they put different preventive recommendations into practice. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional study conducted in 2015 in Switzerland and France. 3400 randomly selected GPs were asked to complete a postal (n=1100) or online (n=2300) questionnaire. GPs who exclusively practiced complementary and alternative medicine were not eligible for the study. 764 GPs (response rate: postal 47%, online 11%) returned the questionnaire (428 in Switzerland and 336 in France). MAIN OUTCOME MEASURES: We investigated how the GPs performed five preventive practices (screening for dyslipidaemia, colorectal and prostate cancer, identification of hazardous alcohol consumption and brief intervention), examining which age group they selected, the screening frequency, the test they used, whether they favoured shared decision for prostate cancer screening and their definition of hazardous alcohol use. RESULTS: A large variability was observed in the way in which GPs provide these practices. 41% reported screening yearly for cholesterol, starting and stopping at variable ages. 82% did not use any test to identify hazardous drinking. The most common responses for defining hazardous drinking were, for men, >=21 drinks/week (24%) and >=4 drinks/occasion for binge drinking (20%), and for women, >=14 drinks/week (28%) and >=3 drinks/occasion (21%). Screening for colorectal cancer, mainly with colonoscopy in Switzerland (86%) and stool-based tests in France (93%), was provided every 10 years in Switzerland (65%) and 2 years in France (91%) to patients between 50 years (87%) and 75 years (67%). Prostate cancer screening, usually with shared decision (82%), was provided yearly (62%) to patients between 50 years (74%) and 75-80 years (32%-34%). CONCLUSIONS: The large diversity in the way these practices are provided needs to be addressed, as it could be related to some misunderstandingof the current guidelines, to barriers for guideline uptake or, more likely, to the absence of agreement between the various recommendations. PMID- 28988187 TI - Changes in UK ophthalmology surgical training: analysis of cumulative surgical experience 2009-2015. AB - OBJECTIVE: To investigate changes in the patterns of cumulative surgical experience for ophthalmologists in the UK following the introduction of a new national training scheme. DESIGN: Retrospective review of all surgical training records submitted to the UK Royal College of Ophthalmologists by trainees for the award of Certificate of Completion of Training (CCT) for the period 2009-2015. SETTING: Secondary level care, UK. PARTICIPANTS: 539 trainees achieving CCT over the 7-year study period. INTERVENTIONS: Higher specialist training or ophthalmology specialist training. OUTCOME MEASURES: Number of CCT awards by years and procedures performed for cataract surgery, strabismus, corneal grafts, vitreoretinal (VR) procedures, oculoplastics and glaucoma. RESULTS: Cataract surgical experience showed little change with median number performed/performed supervised (P/PS) 592, IQR: 472-738; mean: 631. Similarly, the median number of strabismus (P/PS 34), corneal grafts (assisted, 9) and VR procedures (assisted, 34) appeared constant. There was a trend towards increasing surgical numbers for oculoplastics (median 116) and glaucoma (57). Overall case numbers for ophthalmic specialist training (OST) trainees (7-year training programme) were higher than higher surgical training (HST) trainees (4.5-year programme) with the exception of squint (P/PS), corneal grafts (P/PS) and VR cases (P/PS). CONCLUSIONS: Overall case numbers reported at time of CCT application appear stable or with a marginal trend towards increasing case numbers. HST (4.5-year programme) case numbers do not include those performed before entry to HST, and although case numbers tended to be higher for OST trainees (7-year programme) compared with HST trainees, they were not proportionately so. PMID- 28988188 TI - Enterobius vermicularis (pinworm) infestation in a child presenting with symptoms of acute appendicitis: a wriggly tale! AB - Acute appendicitis is the most common surgical emergency worldwide. However, it can still present a challenging diagnosis especially in the young, elderly and those individuals of reproductive age, thus encompassing a wide spectrum of varied clinical presentations. Parasitic infections of the appendix are a rare cause of acute appendicitis. However, they must be considered in children presenting with abdominal pain. We report a case of Enterobius vermicularis infestation mimicking the features of acute appendicitis in a 10-year-old girl. This case is a cautionary reminder of the importance of considering E. vermicularis infestation in children presenting with abdominal pain, but who do not have a significantly raised white cell count or high Alvarado scores. A history of anal pruritus is the most characteristic symptom, but the parasites can cause severe abdominal pain mimicking appendicitis. Prompt recognition and a high clinical index of suspicion are required to prevent an unnecessary appendicectomy. Caution is advised when performing a laparoscopic appendectomy, as in our case, to prevent contamination of the peritoneum. This infestation is easily treatable with mebendazole. PMID- 28988189 TI - Recurrent chylothorax: a clinical mystery. AB - Chylothorax is an unusual cause of pleural effusion, typically caused by trauma or malignancy. Waldenstrom's macroglobulinaemia (WM) is a clinicopathological entity demonstrating lymphoplasmacytic lymphoma in the bone marrow with an IgM monoclonal gammopathy in the blood. Recurrent chylous effusions are often resistant to conservative treatment and may require surgical intervention. We present a unique case of a 50-year-old woman with recurrent chylothorax secondary to WM that completely resolved with ibrutinib therapy. To our knowledge, this is the eighth such case reported in literature and the first case of successful resolution of chylothorax with monoclonal antibody therapy. PMID- 28988190 TI - The outcome of patients in traumatic cardiac arrest presenting to deployed military medical treatment facilities: data from the UK Joint Theatre Trauma Registry. AB - BACKGROUND: The UK military was continuously engaged in armed conflict in Iraq and Afghanistan between 2003 and 2014, resulting in 629 UK fatalities. Traumatic cardiac arrest (TCA) is a precursor to traumatic death, but data on military outcomes are limited. In order to better inform military treatment protocols, the aim of this study was to define the epidemiology of TCA in the military population with a particular focus on survival rates and injury patterns. METHODS: A retrospective database analysis of the UK Joint Theatre Trauma Registry was undertaken. Patients who were transported to a UK deployed hospital between 2003 and 2014 and suffered TCA were included. Those patients injured by asphyxiation, electrocution, burns without other significant trauma and drowning were excluded. Data included mechanism of injury, Injury Severity Score (ISS), Abbreviated Injury Scale (AIS) for each body region and survival to deployed (Role 3) field hospital discharge. RESULTS: 424 TCA patients were identified during the study period; median age was 23 years, with a median ISS of 45. The most common mechanism of injury was explosive (55.7%), followed by gunshot wound (38.9%), road traffic collision (3.5%), crush (1.7%) and fall (0.2%). 45 patients (10.6% (95% CI 8.0% to 13.9%)) survived to deployed (Role 3) hospital discharge. The most prevalent body region with a severe to maximum AIS injury was the head, followed by the lower limbs, thorax and abdomen. Haemorrhage secondary to abdominal and lower limb injury was associated with survival; traumatic brain injury was associated with death. CONCLUSIONS: This study has shown that short term survival from TCA in a military population is 10.6%. With appropriate and aggressive early management, although unlikely, survival is still potentially possible in military patients who suffer traumatic cardiac arrest. PMID- 28988191 TI - Pathways between depression, substance use and multiple sex partners among Northern and Indigenous young women in the Northwest Territories, Canada: results from a cross-sectional survey. AB - OBJECTIVES: Sexual and mental health disparities exist in the Northwest Territories (NWT) compared with other Canadian regions. STI rates are 10-fold higher, and youth suicide rates double the Canadian average. Scant research has examined associations between mental and sexual health among youth in the NWT. The study objective was to explore pathways from depression to multiple sex partners (MSP) among young women in the NWT, Canada. METHODS: We implemented a cross-sectional survey in 2015-2016 with a venue-based recruitment sample of young women aged 13-17 attending secondary schools in 17 NWT communities. We conducted path analysis to test a conceptual model examining associations between depression and a history of MSP, examining substance use and peer support as mediators. RESULTS: Participants (n=199; mean age: 13.8, SD: 1.27) mostly identified were Indigenous (n=154; 77.4%) and one-fifth (n=39; 20.5%) were sexually diverse/non-heterosexual. Almost two-thirds (n=119; 63.3%) reported depression symptoms. One-quarter (n=53; 26.6%) were currently dating, and 16.1% (n=32) reported a lifetime history of >1 sex partner (classified as having MSP). There was no direct effect between depression and MSP (beta=0.189, p=0.087, 95% CI 0.046 to 0.260). Depression had a direct effect on substance use (beta=0.023, p<0.050, 95% CI 0.118 to 0.500), and an indirect effect on MSP through substance use (beta=0.498, SE=0.10, p<0.001, 95% CI 0.141 to 0.280). Depression was associated with lower peer support (beta=-0.168, p<0.010, 95% CI -0.126 to 0.280); peer support was not associated with MSP (beta=-0.158, p=0.130, 95% CI 0.126 to 0.001). CONCLUSION: This research is among the first to identify mental health factors associated with STI vulnerability among young women in the NWT. Findings demonstrate the importance of addressing depression and substance use in sexual health interventions in Northern contexts. PMID- 28988192 TI - Single-pulse CO2 laser treatment of paraurethral duct dilatation following gonococcal inflammation of the paraurethral glands in men. PMID- 28988193 TI - Using the eSexual Health Clinic to access chlamydia treatment and care via the internet: a qualitative interview study. AB - OBJECTIVE: We developed the eSexual Health Clinic (eSHC), an innovative, complex clinical and public health intervention, embedded within a specialist sexual health service. Patients with genital chlamydia access their results online and are offered medical management via an automated online clinical consultation, leading to antibiotic collection from community pharmacy. A telephone helpline, staffed by Sexual Health Advisers, is available to support patients and direct them to conventional services if appropriate. We sought to understand how patients used this ehealth intervention. METHODS: Within exploratory studies of the eSHC (2014-2015), we conducted in-depth interviews with a purposive sample of 36 patients diagnosed with chlamydia, who had chosen to use the eSHC (age 18-35, 20 female, 16 male). Thematic analysis was conducted. RESULTS: Participants described choosing to use this ehealth intervention to obtain treatment rapidly, conveniently and privately, within busy lifestyles that hindered clinic access. They described completing the online consultation promptly, discreetly and with ease. The information provided online was considered comprehensive, reassuring and helpful, but some overlooked it in their haste to obtain treatment. Participants generally described being able to collect treatment from pharmacies discreetly and promptly, but for some, poor awareness of the eSHC by pharmacy staff undermined their ability to do this. Those unsuitable for remote management, who were directed to clinic, described frustration and concern about health implications and clinic attendance. However, the helpline was a highly valued source of information, assistance and support. CONCLUSION: The eSHC is a promising adjunct to traditional care. Its users have high expectations for convenience, speed and privacy, which may be compromised when transitioning from online to face-to-face elements of the eSHC. Managing expectations and improving implementation of the pharmacy process, could improve their experiences. Positive views on the helpline provide further support for embedding this ehealth intervention within a specialist clinical service. PMID- 28988194 TI - Observational study of the populations accessing rapid point-of-care HIV testing in Winnipeg, Manitoba, Canada, through a retrospective chart review of site records. AB - OBJECTIVES: HIV point-of-care testing (POCT) has been available in Manitoba since 2008. This study evaluated the effectiveness of POCT at identifying individuals with previously unknown HIV status, its effects on clinical outcomes and the characteristics of the populations reached. METHODS: A retrospective database review was conducted for individuals who received HIV POCT from 2011 to 2014. Time to linkage to care and viral load suppression were compared between individuals who tested positive for HIV using POCT and controls identified as positive through standard screening. Testing outcomes for labouring women with undocumented HIV status accessing POCT during labour were also assessed. RESULTS: 3204 individuals received POCT (1055 females (32.9%) and 2149 males (67.1%)), being the first recorded HIV test for 2205 (68.8%). Males were more likely to be targeted with POCT as their first recorded HIV test (adjusted OR (AOR) 1.40). Between the two main test sites (Main Street Project (MSP) and Nine Circles Community Health Centre), MSP tested relatively fewer males (AOR 0.79) but a higher proportion of members of all age groups over 30 years old (AOR 1.83, 2.51 and 3.64 for age groups 30-39, 40-49 and >50, respectively). There was no difference in time to linkage to care (p=0.345) or viral load suppression (p=0.405) between the POCT and standard screening cohorts. Of 215 women presenting in labour with unknown HIV status, one was identified as HIV positive. CONCLUSIONS: POCT in Manitoba has been successful at identifying individuals with previously unknown HIV-positive status. Demographic differences between the two main testing sites support that this intervention is reaching unique populations. Given that we observed no significant difference in time to clinical outcomes, it is reasonable to continue using POCT as a targeted intervention. MESH TERMS: HIV infection; rapid HIV testing; vertical infectious disease transmission; community outreach; service delivery; marginalised populations. PMID- 28988195 TI - EUS-guided fine needle biopsy of pancreatic masses can yield true histology. PMID- 28988196 TI - The oral microbiota in colorectal cancer is distinctive and predictive. AB - BACKGROUND AND AIMS: Microbiota alterations are linked with colorectal cancer (CRC) and notably higher abundance of putative oral bacteria on colonic tumours. However, it is not known if colonic mucosa-associated taxa are indeed orally derived, if such cases are a distinct subset of patients or if the oral microbiome is generally suitable for screening for CRC. METHODS: We profiled the microbiota in oral swabs, colonic mucosae and stool from individuals with CRC (99 subjects), colorectal polyps (32) or controls (103). RESULTS: Several oral taxa were differentially abundant in CRC compared with controls, for example, Streptococcus and Prevotellas pp. A classification model of oral swab microbiota distinguished individuals with CRC or polyps from controls (sensitivity: 53% (CRC)/67% (polyps); specificity: 96%). Combining the data from faecal microbiota and oral swab microbiota increased the sensitivity of this model to 76% (CRC)/88% (polyps). We detected similar bacterial networks in colonic microbiota and oral microbiota datasets comprising putative oral biofilm forming bacteria. While these taxa were more abundant in CRC, core networks between pathogenic, CRC associated oral bacteria such as Peptostreptococcus, Parvimonas and Fusobacterium were also detected in healthy controls. High abundance of Lachnospiraceae was negatively associated with the colonisation of colonic tissue with oral-like bacterial networks suggesting a protective role for certain microbiota types against CRC, possibly by conferring colonisation resistance to CRC-associated oral taxa and possibly mediated through habitual diet. CONCLUSION: The heterogeneity of CRC may relate to microbiota types that either predispose or provide resistance to the disease, and profiling the oral microbiome may offer an alternative screen for detecting CRC. PMID- 28988199 TI - Spatial distribution of pedestrian-motor vehicle collisions before and after pedestrian countdown signal installation in Toronto, Canada. AB - BACKGROUND: Pedestrian countdown signals (PCS) have been installed in many cities over the last 15 years. Few studies have evaluated the effectiveness of PCS on pedestrian motor vehicle collisions (PMVC). This exploratory study compared the spatial patterns of collisions pre and post PCS installation at PCS intersections and intersections or roadways without PCS in Toronto, and examined differences by age. METHODS: PCS were installed at the majority of Toronto intersections from 2007 to 2009. Spatial patterns were compared between 4 years of police-reported PMVC prior to PCS installation to 4 years post installation at 1864 intersections. The spatial distribution of PMVC was estimated using kernel density estimates and simple point patterns examined changes in spatial patterns overall and stratified by age. Areas of higher or lower point density pre to post installation were identified. RESULTS: There were 14 911 PMVC included in the analysis. There was an overall reduction in PMVC post PCS installation at both PCS locations and non-PCS locations, with a greater reduction at non-PCS locations (22% vs 1%). There was an increase in PMVC involving adults (5%) and older adults (9%) at PCS locations after installation, with increased adult PMVC concentrated downtown, and older adult increases occurring throughout the city following no spatial pattern. There was a reduction in children's PMVC at both PCS and non-PCS locations, with greater reductions at non-PCS locations (35% vs 48%). CONCLUSIONS: Results suggest that the effects of PCS on PMVC may vary by age and location, illustrating the usefulness of exploratory spatial data analysis approaches in road safety. The age and location effects need to be understood in order to consistently improve pedestrian mobility and safety using PCS. PMID- 28988197 TI - Vonoprazan prevents ulcer recurrence during long-term NSAID therapy: randomised, lansoprazole-controlled non-inferiority and single-blind extension study. AB - OBJECTIVE: To assess the non-inferiority of vonoprazan to lansoprazole for secondary prevention of non-steroidal anti-inflammatory drug (NSAID)-induced peptic ulcer (PU) and the safety of vonoprazan during extended use. DESIGN: A phase 3, 24-week, multicenter, randomised, double-blind (DB), active-controlled study, followed by a phase 3, >=28 week, multicenter, single-blind, parallel group extension study (EXT) in outpatients (n=642) receiving long-term NSAID therapy who are at risk of PU recurrence. The patients received vonoprazan (10 mg or 20 mg) or lansoprazole 15 mg once daily. For DB, non-inferiority of the proportion of patients with recurrent PU within 24 weeks was analysed by Farrington and Manning test (significance level 2.5%, non-inferiority margin 8.3%; primary endpoint), recurrent PU within 12 weeks, bleeding and time-to-event of PU (secondary endpoint) and treatment-emergent adverse events (TEAEs). For EXT, TEAEs (primary endpoint), recurrent PU and safety (secondary) were assessed up to 104 weeks for patients in the extension study. RESULTS: The non-inferiority of vonoprazan 10 mg and 20 mg to lansoprazole 15 mg was verified (percentage difference -2.2%,95% CI -6.2% to 1.8%, p<0.001; -2.1%,95% CI -6.1% to 2.0%, p<0.001, respectively). The proportion of patients with endoscopically confirmed recurrent PU within 24 weeks was 3.3%, 3.4% and 5.5%, for vonoprazan 10 mg, 20 mg and lansoprazole 15 mg, respectively. No significant safety concerns were identified. CONCLUSION: The non-inferiority of vonoprazan (10 and 20 mg) was verified in patients receiving long-term NSAIDs in DB; it was effective and well tolerated in EXT for longer than 1 year, with a safety profile similar to lansoprazole (15 mg). TRIAL REGISTRATION NUMBERS: NCT01452750, NCT01456260; Results. PMID- 28988198 TI - Wide-field endoscopic mucosal resection versus endoscopic submucosal dissection for laterally spreading colorectal lesions: a cost-effectiveness analysis. AB - OBJECTIVE: To compare the cost-effectiveness of endoscopic submucosal dissection (ESD) and wide-field endoscopic mucosal resection (WF-EMR) for removing large sessile and laterally spreading colorectal lesions (LSLs) >20 mm. DESIGN: An incremental cost-effectiveness analysis using a decision tree model was performed over an 18-month time horizon. The following strategies were compared: WF-EMR, universal ESD (U-ESD) and selective ESD (S-ESD) for lesions highly suspicious for containing submucosal invasive cancer (SMIC), with WF-EMR used for the remainder. Data from a large Western cohort and the literature were used to inform the model. Effectiveness was defined as the number of surgeries avoided per 1000 cases. Incremental costs per surgery avoided are presented. Sensitivity and scenario analyses were performed. RESULTS: 1723 lesions among 1765 patients were analysed. The prevalence of SMIC and low-risk-SMIC was 8.2% and 3.1%, respectively. Endoscopic lesion assessment for SMIC had a sensitivity and specificity of 34.9% and 98.4%, respectively. S-ESD was the least expensive strategy and was also more effective than WF-EMR by preventing 19 additional surgeries per 1000 cases. 43 ESD procedures would be required in an S-ESD strategy. U-ESD would prevent another 13 surgeries compared with S-ESD, at an incremental cost per surgery avoided of US$210 112. U-ESD was only cost-effective among higher risk rectal lesions. CONCLUSION: S-ESD is the preferred treatment strategy. However, only 43 ESDs are required per 1000 LSLs. U-ESD cannot be justified beyond high-risk rectal lesions. WF-EMR remains an effective and safe treatment option for most LSLs. TRIAL REGISTRATION NUMBER: NCT02000141. PMID- 28988200 TI - Supporting injury prevention research: taking stock and moving forward. PMID- 28988201 TI - What matters, when, for whom? three questions to guide population health scholarship. PMID- 28988202 TI - Neighbourhood social trust and youth perceptions of safety during daily activities. AB - Exposure to adverse neighbourhood conditions can negatively impact adolescent well-being and perceived safety. However, the impact of neighbourhood social trust on perceived safety is largely unknown. We studied 139 adolescent men to investigate how their perceptions of safety varied as a function of social trust levels in the neighbourhoods they traversed; neighbourhoods that were not necessarily their own. Adolescents mapped their minute-by-minute activities over a recent day and rated their perceived safety on a 10-point scale during in person interviews. Neighbourhood social trust was measured via a citywide random sample survey. Mixed effects regression showed that, compared with their safety perceptions when in areas of low social trust, older adolescents were 73% more likely to feel unsafe when in areas of medium social trust, and 89% more likely to feel unsafe when in areas of high social trust. Inverse relationships between neighbourhood social trust and adolescents' perceived safety highlight the complex interplay between youth, environmental contexts and safety. PMID- 28988203 TI - Firearms training: what is actually taught? AB - INTRODUCTION: Firearm safety instructors and public health professionals are natural allies in the quest to prevent firearm injuries. We audited basic firearm classes to provide information that can help familiarise public health professionals and others with the content covered. METHODS: With the advice of expert instructors, we created an audit form. Volunteers audited 20 basic firearm classes in seven north-eastern states. RESULTS: All trainers covered a wide variety of safety issues. Some specific basics were covered in 90+% of the classes, including how to safely load/unload a gun, keeping your finger off the trigger until ready to shoot, and being aware of your target and what is behind it. In 50%-75% of the classes, the trainer covered topics such as operating a safety, clearing jams and cartridge malfunctions, and recommended storing guns unloaded and locked when not in use. Few instructors covered firearm suicide prevention (10%) or domestic violence (10%). Most encouraged gun ownership, gun carrying, gun use in self-defence and membership in a gun rights group. DISCUSSION: From a public health standpoint, we would like to see more instructors covering topics such as firearm suicide and alternatives to gun use in self-defence, and to recommend safer storage of firearms. PMID- 28988204 TI - Effect of bisphosphonates on knee replacement surgery. AB - PURPOSE: Bone remodelling as a therapeutic target in knee osteoarthritis (OA) has gained much interest, but the effects of antiresorptive agents on knee OA have been conflicting, with no studies to date examining the effects of bisphosphonate use on the clinically relevant endpoint of knee replacement (KR) surgery. METHODS: We used data from The Health Improvement Network (THIN), a general practitioner electronic medical records representative of the general UK population. We identified older women who had initiated bisphosphonate use after their incident knee OA diagnosis. Each bisphosphonate initiator was propensity score-matched with a non-initiator within each 1-year cohort accrual block. The effect of bisphosphonates on the risk of KR was assessed using Cox proportional hazard regression. Sensitivity analyses to address residual confounding were also conducted. RESULTS: We identified 2006 bisphosphonate initiators, who were matched to 2006 non-initiators(mean age 76, mean body mass index 27), with mean follow-up time of 3 years. The crude incidence rate of KR was 22.0 per 1000 person-years among the initiators, and 29.1 among the non-initiators. Bisphosphonate initiators had 26% lower risk of KR than non-initiators(HR 0.74, 95% CI 0.59 to 0.93); these results were similar when additionally adjusted for potential confounders in the propensity score (HR 0.76, 95% CI 0.60 to 0.95). Results of sensitivity analyses supported this protective effect. CONCLUSIONS: In this population-based cohort of older women with incident knee OA, those with incident bisphosphonate users had lower risk of KR than non-users of bisphosphonates, suggesting a potential beneficial effect of bisphosphonates on knee OA. PMID- 28988205 TI - Response to: 'Spontaneous hypertensive rat exhibits bone and meniscus phenotypes of osteoarthritis: is it an appropriate control for MetS-associated OA?' by Chan and Wen. PMID- 28988206 TI - Cigarette smoking and the risk of systemic lupus erythematosus, overall and by anti-double stranded DNA antibody subtype, in the Nurses' Health Study cohorts. AB - OBJECTIVES: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease, subtyped according to clinical manifestations and autoantibodies. Evidence concerning cigarette smoking and SLE risk has been conflicting. We investigated smoking and SLE risk, overall and by anti-double stranded DNA (dsDNA) presence, in two prospective cohort studies. METHODS: The Nurses' Health Study (NHS) enrolled 121 701 US female nurses in 1976; Nurses' Health Study II (NHSII) enrolled 116 430 in 1989. Lifestyle, environmental and medical data were collected through biennial questionnaires. Incident SLE was confirmed by medical record review. Cox regression models estimated HRs of SLE, overall and by dsDNA subtype, in association with time-varying smoking status and cumulative smoking pack-years through the 2-year cycle prior to diagnosis, controlling for potential confounders. RESULTS: Among 286 SLE cases identified (159 in NHS (1978-2012) and 127 in NHSII (1991-2013)), mean age was 49.2 (10.3) years and 42% were dsDNA+ at SLE diagnosis. At baseline, 45% of women had ever smoked, 51% of whom currently smoked. Compared with never smokers, current smokers had increased dsDNA+ SLE risk (HR 1.86 (1.14-3.04)), whereas past smokers did not (HR 1.31 (0.85-2.00)). Women who smoked >10 pack-years (vs never) had an elevated dsDNA+ SLE risk (HR 1.60(95% CI 1.04 to 2.45)) compared with never smokers. No associations were observed between smoking status or pack-years and overall SLE or dsDNA- SLE. CONCLUSION: Strong and specific associations of current smoking and >10 pack years of smoking with dsDNA+ SLE were observed. This novel finding suggests smoking is involved in dsDNA+ SLE pathogenesis. PMID- 28988207 TI - Leg lean mass correlates with exercise systemic output in young Fontan patients. AB - OBJECTIVE: We previously described lower leg lean mass Z-scores (LLMZ) in Fontan patients associated with worse peak oxygen consumption on metabolic exercise testing. We hypothesised that LLMZ correlates with indexed systemic flow (Qsi) and cardiac index (CI) on exercise cardiac magnetic resonance (eCMR). METHODS: Thirteen patients had LLM measured by dual-energy X-ray absorptiometry within mean 40 (range 0-258) days of eCMR. LLM was converted to sex and race-specific Z scores based on healthy reference data. Ventricular volumes and flow measurements of the ascending and descending (DAO) aorta and superior vena cava (SVC) were obtained by CMR at rest and just after supine ergometer exercise to a heart rate associated with anaerobic threshold on prior exercise test. Baseline and peak exercise measures of Qsi (SVC+DAO/BSA) and CI, as well as change in Qsi and CI with exercise, were compared with LLMZ by linear regression. RESULTS: LLMZ was not correlated with resting flows, stroke volume or CI. There was a strong linear correlation between LLMZ and change in both CI (r=0.77, p=0.002) and Qsi (r=0.73, p=0.005) from rest to exercise. There was also a significant correlation between LLMZ and Qsi at exercise (r=0.70, p=0.008). The correlation between LLMZ and CI at exercise did not reach significance (r=0.3, p=0.07). CONCLUSIONS: In our cohort, there was a strong linear correlation between LLMZ and change in both CI and Qsi from rest to exercise, suggesting that Fontan patients with higher LLMZ may be better able to augment systemic output during exercise, improving performance. PMID- 28988208 TI - Meta-analyses of incomplete trial datasets: unreliable and potentially misleading. PMID- 28988209 TI - Forced air warming during sedation in the cardiac catheterisation laboratory: a randomised controlled trial. AB - OBJECTIVE: Forced air warming (FAW) during general anaesthesia is a safe and effective intervention used to reduce hypothermia. The objective of this study was to determine if FAW reduces hypothermia when used for procedures performed with sedation in the cardiac catheterisation laboratory. METHODS: A parallel group randomised controlled trial was conducted. Adults receiving sedation in a cardiac catheterisation laboratory at two sites were randomised to receive FAW or usual care, which involved passive warming with heated cotton blankets. Hypothermia, defined as a temperature less than 36 degrees C measured with a sublingual digital thermometer after procedures, was the primary outcome. Other outcomes were postprocedure temperature, shivering, thermal comfort and major complications. RESULTS: A total of 140 participants were randomised. Fewer participants who received FAW were hypothermic (39/70, 56% vs 48/69, 70%, difference 14%; adjusted RR 0.75, 95% CI=0.60 to 0.94), and body temperature was 0.3 degrees C higher (95% CI=0.1 to 0.5, p=0.004). FAW increased thermal comfort (63/70, 90% vs51/69, 74% difference 16%, RR 1.21, 95% CI=1.04 to 1.42). The incidence of shivering was similar (3/69, 4% vs 0/71 0%, difference 4%, 95% CI= 1.1 to 9.8). One patient in the control group required reintervention for bleeding. No other major complications occurred. CONCLUSION: FAW reduced hypothermia and improved thermal comfort. The difference in temperature between groups was modest and less than that observed in previous studies where use of FAW decreased risk of surgical complications. Therefore, it should not be considered clinically significant. TRIAL REGISTRATION NUMBER: ACTRN12616000013460. PMID- 28988210 TI - An unusual echo after ventricular tachycardia ablation. PMID- 28988212 TI - Updated 2017 European and American guidelines for prosthesis type and implantation mode in severe aortic stenosis. PMID- 28988213 TI - Management of pneumatosis intestinalis in children over the age of 6 months: a conservative approach. AB - BACKGROUND: Pneumatosis intestinalis (PI) is an uncommon and poorly understood condition. Although it can be an incidental finding in asymptomatic individuals, it can also be secondary to life-threatening bowel ischaemia and sepsis. In premature infants, it is a pathognomonic sign of necrotising enterocolitis. There is no consensus regarding management and long-term outcome of children with PI. AIM: Review of our experience of PI in children beyond the early infantile period. METHODS: Retrospective review of patient's records and radiological images from 2013 to 2015. RESULTS: Eighteen patients (three girls) had radiologically confirmed PI. The median age was 4.5 years (range 8 months-13 years). Background medical conditions (number): short bowel syndrome (one), congenital heart disease (two), sickle cell disease (one), epilepsy (three), cerebral palsy (six), myotonic dystrophy (four) and peroxisomal biogenesis defect (one).Six children (33%) presented with abdominal distension, four (22%) with abdominal pain, three (17%) with bilious vomiting, two (11%) with diarrhoea and one (6%) with rectal bleeding. Two (11%) were asymptomatic. One had air in portal vein and two had pneumoperitoneum.All patients with symptomatic PI were treated conservatively with successful outcome and complete resolution of PI. None required surgical intervention. CONCLUSION: PI in children who are not on chemotherapy or immunosuppressant appears to follow a benign course and is responsive to conservative management. In contrast to adults, portal venous gas and pneumoperitoneum do not predict the need for surgical intervention. PMID- 28988211 TI - Menopausal age, postmenopausal hormone therapy and incident atrial fibrillation. AB - OBJECTIVE: Limited data exist on the association between menopause and atrial fibrillation (AF). We sought to examine the relationship between menopausal age, postmenopausal hormone therapy (PHT) use and incident AF. METHODS: The Women's Health Study (WHS) enrolled 39 876 female health professionals between 1992 and 1995. We prospectively examined 30 034 women in WHS using Cox proportional-hazard models. Participants were free of cardiovascular disease and AF at baseline and had not undergone hysterectomy without bilateral oophorectomy prior to menopause. Incident AF was confirmed by medical record review. RESULTS: At baseline, median age was 53 years (IQR 49-60), median menopausal age was 50 years (IQR 46-52) and 14 415 (48.0%) had prior PHT use. Over a median follow-up of 20.5 years, 1350 AF events occurred. In multivariable analysis, relative hazards for AF were lower among women with younger age at menopause but did not differ significantly from women with the oldest menopausal age (<45: HR 0.82, 95% CI 0.67 to 1.02; 45-49: HR 0.90, 95% CI 0.74 to 1.08; 50-54: HR 0.89, 95% CI 0.75 to 1.06; >54 years: referent). Use of oestrogen-alone PHT, but not oestrogen and progesterone, was independently associated with AF risk (HR 1.22; 95% CI 1.02 to 1.45 vs HR 1.04; 95% CI 0.86 to 1.26). This relationship was not attenuated by intermediary cardiovascular events. CONCLUSIONS: In this large prospective study, menopausal age was not significantly related to incident AF, while use of oestrogen monotherapy was associated with increased AF risk. Our findings suggest a pathophysiological link between unopposed oestrogen exposure and AF in women. CLINICAL TRIAL REGISTRATION: NCT000000479; Post-results. PMID- 28988214 TI - Integrating primary eye care into global child health policies. AB - Globally, approximately 75% of blind children live in low-income countries (LICs). Almost half of blindness and low vision in LICs is due to avoidable causes such as corneal scarring from measles infection, vitamin A deficiency disorders, use of harmful traditional eye remedies, ophthalmia neonatorum and cataract. PMID- 28988215 TI - Biosimilar infliximab use in paediatric IBD. AB - BACKGROUND: Biosimilar infliximab became available in the UK in 2015. Paediatric experience to date on its use is limited. We prospectively evaluated the safety and efficacy of biosimilar infliximab (Remsima) in two paediatric gastroenterology networks in patients with inflammatory bowel disease. METHODS: Prospective clinical data were collected from laboratory reports, electronic patient records and case notes of 40 patients starting Remsima for the first time. Disease activity scores together with blood and stool biomarkers were used to assess response. RESULTS: Our data set highlights that Remsima was associated with a significant clinical and biochemical improvement (p<0.01 or less for all parameters assessed) in Crohn's disease post induction. There were no significant safety issues noted. The total cost saving was L47 800, representing a 38% reduction from originator. CONCLUSION: We found that biosimilar infliximab is as effective as originator infliximab and its use is associated with significant cost savings. PMID- 28988216 TI - Efficacy and treatment costs of zoledronate versus pamidronate in paediatric osteoporosis. AB - Intravenous pamidronate has been used in the treatment of osteogenesis imperfecta (OI) in children for over 20 years. The more potent zoledronate is an attractive alternative as it is administered less frequently. This study compares the clinical efficacy of intravenous pamidronate (1.5 mg/kg/day over 2 days, every 3 months) versus zoledronate (0.05 mg/kg/dose every 6 months) in 40 children (20 per group) with mild to moderate OI and the treatment costs of the two drugs in a tertiary centre for children with osteoporosis. Lumbar spine bone mineral density and fracture rate did not differ between drug groups following 1 and 2 years of treatment, respectively. Total cost per treatment course per patient was L1157 for pamidronate and L498 for zoledronate. Therefore, zoledronate is a considerably cheaper alternative to pamidronate with comparable efficacy, resulting in substantial annual savings for healthcare providers and a more convenient option for patients due to fewer hospital visits. PMID- 28988217 TI - Population-level impact of infant 10-valent pneumococcal conjugate vaccination on adult pneumonia hospitalisations in Finland. AB - INTRODUCTION: Limited data are available on population-level herd effects of infant 10-valent pneumococcal conjugate vaccine (PCV10) programmes on pneumonia. We assessed national trends in pneumococcal and all-cause pneumonia hospitalisations in adults aged >=18 years, before and after infant PCV10 introduction in 2010. METHODS: Monthly hospitalisation rates of International Statistical Classification of Diseases, 10th revision (ICD-10)-coded primary discharge diagnoses compatible with pneumonia from 2004-2005 to 2014-2015 were calculated with population denominators from the population register. Trends in pneumonia before and after PCV10 introduction were assessed with interrupted time series analysis. Rates during the PCV10 period were estimated from adjusted negative binomial regression model and compared with those projected as continuation of the pre-PCV10 trend. All-cause hospitalisations were assessed for control purposes. RESULTS: Before PCV10, the all-cause pneumonia rate in adults aged >=18 years increased annually by 2.4%, followed by a 4.7% annual decline during the PCV10 period. In 2014-2015, the overall all-cause pneumonia hospitalisation rate was 109.3/100 000 (95% CI 96.5 to 121.9) or 15.4% lower than the expected rate. A significant 6.7% decline was seen in persons aged >=65 years (131.5/100 000), which translates to 1456 fewer pneumonia hospitalisations annually. In comparison, hospitalisations other than pneumonia decreased by 3.5% annually throughout the entire study period. CONCLUSION: These national data suggest that herd protection from infant PCV10 programme has reversed the increasing trend and substantially decreased all-cause pneumonia hospitalisations in adults, particularly the elderly. PMID- 28988218 TI - Prediction of long-term outcome subtypes in ARDS: first steps towards personalised medicine in critical care. PMID- 28988219 TI - Differences in levels of albumin, ALT, AST, gamma-GT and creatinine in frail, moderately healthy and healthy elderly individuals. AB - BACKGROUND: Reference intervals are widely used as decision tools, providing the physician with information about whether the analyte values indicate ongoing disease process. Reference intervals are generally based on individuals without diagnosed diseases or use of medication, which often excludes elderly. The aim of the study was to assess levels of albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine and gamma-glutamyl transferase (gamma-GT) in frail, moderately healthy and healthy elderly indivuduals. METHODS: Blood samples were collected from individuals >80 years old, nursing home residents, in the Elderly in Linkoping Screening Assessment and Nordic Reference Interval Project, a total of 569 individuals. They were divided into three cohorts: frail, moderately healthy and healthy, depending on cognitive and physical function. Albumin, ALT, AST, creatinine and gamma-GT were analyzed using routine methods. RESULTS: Linear regression predicted factors for 34% of the variance in albumin were activities of daily living (ADL), gender, stroke and cancer. ADLs, gender and weight explained 15% of changes in ALT. For AST levels, ADLs, cancer and analgesics explained 5% of changes. Kidney disease, gender, Mini Mental State Examination (MMSE) and chronic obstructive pulmonary disease explained 25% of the variation in creatinine levels and MMSE explained three per cent of gamma-GT variation. CONCLUSIONS: Because a group of people are at the same age, they should not be assessed the same way. To interpret results of laboratory tests in elderly is a complex task, where reference intervals are one part, but far from the only one, to take into consideration. PMID- 28988220 TI - Laboratory performance of sweat conductivity for the screening of cystic fibrosis. AB - BACKGROUND: There are several complementary English-language guidelines for the performance of the sweat chloride test. These guidelines also incorporate information for the collection of conductivity samples. However, recommendations for the measurement and reporting of sweat conductivity are less clear than for sweat chloride. The aim of the study was to develop an understanding of the testing and reporting practices of sweat conductivity in Australasian laboratories. METHODS: A survey specifically directed at conductivity testing was sent to the 12 laboratories registered with the Royal College of Pathologists of Australasia Quality Assurance Programs. RESULTS: Nine (75%) laboratories participated in the survey, seven of whom used Wescor Macroduct(r) for collecting sweat and the Wescor SWEAT.CHEKTM for conductivity testing, and the remaining two used the Wescor Nanoduct(r). There was considerable variation in frequency and staffing for this test. Likewise, criteria about which patients it was inappropriate to test, definitions of adequate collection sweat rate, cutoffs and actions recommended on the basis of the result showed variations between laboratories. CONCLUSIONS: Variations in sweat conductivity testing and reporting reflect many of the same issues that were revealed in sweat chloride test audits and have the potential to lead to uncertainty about the result and the proper action in response to the result. We recommend that sweat testing guidelines should include clearer statements about the use of sweat conductivity. PMID- 28988221 TI - Cocos nucifera water improves metabolic functions in offspring of high fat diet fed Wistar rats. AB - BACKGROUND: Maternal high fat diet has been implicated in the aetiology of metabolic diseases in their offspring. The hypolipidaemic actions of Cocos nucifera water improve metabolic indices of dams consuming a high fat diet during gestation. This study investigated the effects of C. nucifera water on metabolism of offspring of dams exposed to high fat diet during gestation. METHODS: Four groups of pregnant Wistar rat dams (n=6) were treated orally from Gestation Day (GD) 1 to GD 21 as follows: standard rodent feed+10 mL/kg distilled water (Control), standard rodent feed+10 mL/kg C. nucifera water, high fat feed+10 mL/kg distilled water (high fat diet), and high fat feed+10 mL/kg C. nucifera water (high fat diet+C. nucifera water). The feeds were given ad libitum and all dams received standard rodent feed after parturition. Fasting blood glucose was measured in offspring before being euthanized on Postnatal Day (PND) 120. Serum insulin, leptin, lipid profile and liver enzymes were measured. RESULTS: Serum total cholesterol (TC), insulin, alanine transaminase (ALT) and alkaline phosphatase levels were significantly increased (p<0.05) in high fat diet offspring compared with controls. Similar changes were not observed in high fat diet+C. nucifera water offspring. CONCLUSIONS: Results suggest that the adverse effects of maternal high fat diet on offspring's metabolism can be ameliorated by C. nucifera water. PMID- 28988222 TI - An isobolographic analysis of the anti-nociceptive effect of geraniin in combination with morphine or diclofenac. AB - BACKGROUND: Geraniin, a dehydroellagitannin, is a major component of the aqueous extract of the aerial parts of Phyllanthus muellerianus (Kuntze) Exell. (Euphorbiaceae). Several Phyllanthus species are traditionally used for painful disorders. The anti-nociceptive effects of the aqueous extract of the aerial parts of P. muellerianus and of geraniin have been scientifically established. The aim of the paper is to determine whether a combination of geraniin and diclofenac or geraniin and morphine leads to better anti-nociceptive effects. METHODS: The nature of the interactions of morphine and diclofenac with geraniin was evaluated by undertaking the isobolographic analysis. Mice were treated with geraniin (3-30 mg/kg), morphine (1-10 mg/kg), and diclofenac (10-100 mg/kg) to obtain the ED50 values of the agents in the formalin test. Dose-response curves were then obtained and analyzed after the co-administration of geraniin with morphine or diclofenac in fixed ratio (1:1) combinations based on specific fractions (1/2, 1/4, and 1/8) of their respective ED50 values for the formalin test. RESULTS: Geraniin was less potent than morphine but more potent than diclofenac in the formalin-induced nociception. The isobolographic analysis of geraniin/morphine (G/M) and geraniin/diclofenac combinations (G/D) at different fractions revealed the potentiation of their anti-nociceptive effects. The degrees of potentiation, which were calculated as interaction indices, showed synergism for both combinations in both phase I (G/M: 0.040, G/D: 0.017) and phase II (G/M: 0.004, G/D: 0.002) of the formalin test. CONCLUSIONS: The present study demonstrates synergism for the co-administration of geraniin with both morphine and diclofenac. PMID- 28988223 TI - Makorin ring finger 3 gene analysis in Koreans with familial precocious puberty. AB - BACKGROUND: Precocious puberty is known as an idiopathic, sporadic disease. Recently, specific mutations have been shown to cause familial central precocious puberty (CPP). The makorin ring finger 3 (MKRN3) gene plays a key role in puberty; loss-of-function mutations in the gene trigger familial CPP. To date, most described patients have been Western; few Asians with CPP have been documented. OBJECTIVE: To identify MKRN3 gene mutations or polymorphisms in Korean patients with familial CPP. METHODS: 26 patients with CPP and their parents (total 13 families) were recruited. We measured endocrine and auxological parameters, and sequenced all MKRN3 exons. RESULTS: We found no MKRN3 mutations. Two MKRN3 exon polymorphisms were identified. The g.23566445 C/T polymorphism was found in eight families; a novel single nucleotide polymorphism (SNP) g.23567001 A/C was found in one family. These variants are synonymous SNPs; their functional roles remain unknown. CONCLUSIONS: MKRN3 mutation is uncommon in Korean patients with familial CPP. Ethnic variation in the MKRN3 mutational status is thus evident. PMID- 28988224 TI - Oral health status of children with type 1 diabetes: a comparative study. AB - BACKGROUND: The aim of this study was to compare the oral health status of children with type 1 diabetes and healthy controls. METHODS: This comparative study involved 64 children, 32 children with type 1 diabetes and 32 age- and gender-matched controls. Oral health examination was conducted using WHO criteria. Dental caries experience was recorded using DMFT/dmft index and periodontal parameters were assessed using plaque, gingivitis, gingival bleeding and calculus indexes. Dental caries and periodontal parameters between the two groups were compared using the Mann-Whitney U-test. RESULTS: Children with diabetes exhibited significantly greater plaque deposits (p=0.01) and a higher mean plaque index (p<0.01), when compared to healthy subjects. No significant difference in DMFT and dmft scores, mean bleeding index, calculus index and gingival index was found between the two groups. CONCLUSIONS: Children with type 1 diabetes had a poor oral health status with greater plaque accumulation than children without diabetes. PMID- 28988225 TI - Persistent de Quervain tenosynovitis induced by somatotropin treatment. AB - BACKGROUND: Growth hormone deficiency is a well-known clinical entity that is usually treated with somatotropin (growth hormone). Growth hormone has some frequent side effects such as intracranial hypertension, lymphedema and diabetes mellitus. CASE PRESENTATION: We report the case of a 14-year-old girl with a history of wrist pain and clumsiness. Magnetic resonance imaging revealed de Quervain tenosynovitis. The patient had a history of using growth hormones for 12 months. We conservatively managed the patient with corticosteroid injections and oral nonsteroidal anti-inflammatory drugs and followed the course. However, the conservative treatment methods failed, and we recommended surgery, which was rejected. She was given nonsteroidal anti-inflammatory drugs and was followed up for 2 years, at the end of which her visual analog scale had decreased from 80 to 50. CONCLUSIONS: To the best of our knowledge this is the first case of de Quervain tenosynovitis related to somatotropin treatment. Physicians should consider the possibility of musculoskeletal side effects after somatotropin treatment. PMID- 28988226 TI - Severe complications after initial management of hyperglycemic hyperosmolar syndrome and diabetic ketoacidosis with a standard diabetic ketoacidosis protocol. AB - Hyperglycemic hyperosmolar syndrome (HHS) is a clinical entity not identical to diabetic ketoacidosis (DKA), and with a markedly higher mortality. Children with HHS can also present with concomitant DKA. Patients with HHS (with or without DKA) are profoundly dehydrated but often receive inadequate fluid resuscitation as well as intravenous insulin therapy based on traditional DKA protocols, and this can lead to devastating consequences. In this article, we briefly review HHS along with a report of an adolescent who presented with HHS and DKA and was initially managed as DKA. She went into hypotensive shock and developed severe, multiorgan failure. A thorough understanding of the pathophysiology of HHS and its differences from DKA in terms of initial management is crucial to guide management and improve outcomes. Additionally, fluid therapy in amounts concordant with the degree of dehydration remains the mainstay therapy. PMID- 28988227 TI - Thyroid hormone levels in late preterm, early term and term infants: a study with healthy neonates revealing reference values and factors affecting thyroid hormones. AB - BACKGROUND: Thyroid function tests in neonates have been challenging to interpret because their levels are affected by several neonatal and delivery-related factors. The aim of the study was to evaluate reference values of thyroxine (T4) and thyrotropin (TSH) levels in different gestational age groups and to demonstrate the affect of perinatal factors on thyroid hormones. METHODS: Medical records of 7616 neonates whose gestational age ranges between 34 and 42 weeks were analyzed retrospectively. Gender, mode of delivery, gestational age, postnatal age and birth weight were noted together with TSH and T4 levels. RESULTS: Gestational age (r=0.14, p<0.001) and birth weight (r=0.12, p<0.001) had positive correlation with T4 levels, whereas they had no effect on TSH levels. Males had higher TSH and lower T4 levels (p=0.001 for both) compared with females. T4 levels of babies born via vaginal delivery were lower than the ones born via cesarean section (p=0.01). Multivariable analysis yielded gestational age as the only factor affecting T4 levels (p<0.001). T4 and TSH levels based on 2.5-97.5 percentile cutoffs according to gestational age were presented. CONCLUSIONS: The thyroid hormone ranges given in this study can help pediatricians to interpret the thyroid hormone results with ease. PMID- 28988228 TI - The relationship between non-alcoholic fatty liver disease and small intestinal bacterial overgrowth among overweight and obese children and adolescents. AB - BACKGROUND: The increasing rate of obesity and overweight among children has highlighted nonalcoholic fatty liver disease (NAFLD) as the most common cause of chronic pediatric liver diseases. There are many publications supporting the idea that gut microbiota is altered in NAFLD. The aim of this study was to evaluate the prevalence of NAFLD among overweight and obese children with and without small intestinal bacterial overgrowth (SIBO) compared to a control group and to assess if intestinal dysbiosis represents a risk factor for NAFLD. METHODS: One hundred and twenty-five overweight and obese children aged 10-18 years and 120 controls matched for age and gender were enrolled. SIBO was assessed by glucose hydrogen breath test (GHBT) in all subjects. NAFLD was assessed in all children using abdominal imaging and laboratory findings. RESULTS: Of 125 obese children enrolled, 47 (37.6%) presented intestinal dysbiosis and 78 (62.4%) were SIBO negative. Only four (3.3%) controls were SIBO positive. NAFLD was detected in 28/47 (59.5%) of the SIBO positive obese group, compared to 8/78 (10.2%) of the SIBO negative obese group (p<0.001) and 0/120 (0%) controls (p<0.001). Children from the SIBO positive obese group had higher rates of elevated aminotransferases levels: aspartate aminotransferases (ASAT) (53.1% vs. 6.4%; p<0.001) and alanine aminotransferase (ALAT) (59.5% vs. 7.6%; p<0.001), hypertension (23.4% vs. 5.1%; p=0.002) and metabolic syndrome (44.6% vs. 9%; p=0.002) compared to the SIBO negative obese group. CONCLUSIONS: Obese children with SIBO have an increased risk for developing NAFLD. The relationship between intestinal dysbiosis and diet can influence the gut-liver axis. PMID- 28988229 TI - Studying Kidney Disease Using Tissue and Genome Engineering in Human Pluripotent Stem Cells. AB - Kidney morphogenesis and patterning have been extensively studied in animal models such as the mouse and zebrafish. These seminal studies have been key to define the molecular mechanisms underlying this complex multistep process. Based on this knowledge, the last 3 years have witnessed the development of a cohort of protocols allowing efficient differentiation of human pluripotent stem cells (hPSCs) towards defined kidney progenitor populations using two-dimensional (2D) culture systems or through generating organoids. Kidney organoids are three dimensional (3D) kidney-like tissues, which are able to partially recapitulate kidney structure and function in vitro. The current possibility to combine state of-the art tissue engineering with clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated systems 9 (Cas9)-mediated genome engineering provides an unprecedented opportunity for studying kidney disease with hPSCs. Recently, hPSCs with genetic mutations introduced through CRISPR/Cas9 mediated genome engineering have shown to produce kidney organoids able to recapitulate phenotypes of polycystic kidney disease and glomerulopathies. This mini review provides an overview of the most recent advances in differentiation of hPSCs into kidney lineages, and the latest implementation of the CRISPR/Cas9 technology in the organoid setting, as promising platforms to study human kidney development and disease. PMID- 28988230 TI - Urinary Kidney Injury Molecule-1 but Not Urinary Neutrophil Gelatinase Associated Lipocalin Is Increased after Short Maximal Exercise. AB - BACKGROUND AND AIMS: Urinary neutrophil gelatinase associated lipocalin (uNGAL) and urinary kidney injury molecule-1 (uKIM-1) are markers of acute kidney injury. The albuminuria is a well-known abnormality after physical exercise. The aim of this study was to investigate changes in uNGAL and uKIM-1 after intensive exercise causing albuminuria. METHODS: The study population consisted of 19 participants (10 males and 9 females). The mean age of participants was 35.74 years. All were fit amateur runners; the mean body mass index was 21.99 in females and 24.71 in males. The subjects underwent a graded treadmill exercise test (GXT) according to the Bruce protocol. Maximal oxygen consumption (VO2max) was measured. Immediately before and after the test urine was collected. Urinary creatinine, albumin, NGAL, and KIM-1 were measured. Albumin to creatinine (ACR), KIM-1 to creatinine (KCR), and NGAL to creatinine (NCR) ratios were calculated. RESULTS: The mean VO2max was 53.68 in females and 59.54 mL/min/kg in males. Albuminuria and ACR were significantly higher after exercise. An increase in the ACR from 8.82 to 114.35 mg/g (p < 0.01) was observed. uKIM-1 increased significantly after exercise from 849.02 to 1,243.26 pg/mL (p < 0.05). KCR increased from 1,239.1 to 1,725.9 ng/g but without statistical significance (p = 0.07). There were no statistical changes in pre- and post-run uNGAL levels. There was no correlation between post-GXT albuminuria and uKIM-1. CONCLUSIONS: uKIM-1 is a very sensitive marker of kidney dysfunction. In our study, uKIM-1 increased significantly after a very short period of exercise. It is not clear if the increase in KIM-1 is caused by post-exercise albuminuria. PMID- 28988231 TI - Principles of Current Vertebrate Neuromorphology. AB - Causal analysis of molecular patterning at neural plate and early neural tube stages has shown that the central nervous system (CNS) of vertebrates is essentially organized into transverse neural segments or neuromeres and longitudinal zones which follow the curved axis of the brain. The intersection of the longitudinal and transverse patterning processes in the embryonic brain leads to the formation of a checkerboard pattern of distinct progenitor domains called "fundamental morphological units" (FMUs). The topologically invariant pattern formed by the ventricular surfaces of the FMUs of a given taxon represents the "Bauplan" or "blueprint" of the brain of that taxon. The FMUs initially represent thin epithelial fields; during further development they are transformed into three-dimensional radial units, extending from the ventricular surface to the meningeal surface. It is of note that the boundaries of the neuromeres, longitudinal zones, and radial units all strictly adhere to a non-Cartesian coordinate system inherent to the CNS of all vertebrates. The major neural histogenetic processes, including cellular proliferation, radial migration, and differentiation, as well as the formation of grisea (cell masses, nuclei, and cortices), occur principally within the confines of the FMUs, although tangential migration may also take cells to distant sites. Hence, recognition and delimitation of these units is essential for the identification and interpretation of grisea. An outline of the procedure to be followed in these processes of identification and interpretation is presented, and a list of the pertinent homology criteria is provided. PMID- 28988232 TI - Clearance of Selected Plasma Cytokines with Continuous Veno-Venous Hemodialysis Using Ultraflux EMiC2 versus Ultraflux AV1000S. AB - BACKGROUND: High cutoff hemofilters might support the restoration of immune homeostasis in systemic inflammation by depleting inflammatory mediators from the circulation. METHODS: Interleukin (IL)-6, IL-8, IL-10, and tumor necrosis factor alpha depletion was assessed in 30 sepsis patients with acute renal failure using continuous veno-venous hemodialysis with high cutoff versus standard filters (CVVHD-HCO vs. CVVHD-STD) over 48 h. RESULTS: The transfer of IL-6 and IL-8 was significantly higher for CVVHD-HCO, as shown by increased IL-6 and IL-8 effluent concentrations. The mean plasma cytokine concentrations decreased over time for all cytokines without detectable differences for the treatment modalities. No transfer of albumin was observed for either of the filters. C-reactive protein remained stable over time and did not differ between CVVHD-HCO and CVVHD-STD, while procalcitonin decreased significantly over 48 h for both treatment modalities. CONCLUSION: CVVHD-HCO achieved enhanced removal of IL-6 and IL-8 as compared to CVVHD-STD, without differentially reducing plasma cytokine levels. PMID- 28988234 TI - Dynamics of Goldfish Subregional Hippocampal Pallium Activity throughout Spatial Memory Formation. AB - The teleost fish hippocampal pallium, like the hippocampus of tetrapods, is essential for relational map-like spatial memories. In mammals, these relational memories involve the dynamic interactions among different hippocampal subregions and between the hippocampus-neocortex network, which performs specialized operations such as memory encoding and retrieval. However, how the teleost hippocampal homologue operates to achieve comparably sophisticated spatial cognition capabilities is largely unknown. In the present study, the progressive changes in the metabolic activity of the pallial regions that have been proposed as possible homologues of the mammalian hippocampus were monitored in goldfish. Quantitative cytochrome oxidase histochemistry was used to measure the level of activation along the rostrocaudal axis of the ventral (Dlv) and dorsal parts of the dorsolateral division (Dld) and in the dorsoposterior division (Dp) of the goldfish telencephalic pallium throughout the time course of the learning process of a spatial memory task. The results revealed a significant increase in spatial memory-related metabolic activity in the Dlv, but not in the Dld, suggesting that the Dlv, but not the Dld, is comparable to the amniote hippocampus. Regarding the Dlv, the level of activation of the precommissural Dlv significantly increased at training onset but progressively declined to finally return to the basal pretraining level when the animals mastered the spatial task. In contrast, the commissural Dlv activation persisted even when the acquisition phase was completed and the animal's performance reached an asymptotic level. These results suggest that, like the dentate gyrus of mammals, the goldfish precommissural Dlv seems to respond nonlinearly to increments of change in sensory input, performing pattern separation under highly dissimilar input patterns. In addition, like the CA3 of mammals, the commissural Dlv likely operates in a continuum between two modes, a pattern separation or storage operation mode at early acquisition when the change in the sensory input is high, probably driven by the precommissural Dlv output, and a pattern completion or recall operation mode when the animals have mastered the task and the change in sensory input is small. Finally, an unexpected result of the present study is the persistent activation of the area Dp throughout the complete spatial task training period, which suggests that the Dp could be an important component of the pallial network involved in spatial memory in goldfish, and supports the hypothesis proposing that the Dp is a specialized part of the hippocampal pallium network. PMID- 28988236 TI - Vertebrate Sensory Systems and Brains: From Genes to Behavior. PMID- 28988233 TI - Sensing External and Self-Motion with Hair Cells: A Comparison of the Lateral Line and Vestibular Systems from a Developmental and Evolutionary Perspective. AB - Detection of motion is a feature essential to any living animal. In vertebrates, mechanosensory hair cells organized into the lateral line and vestibular systems are used to detect external water or head/body motion, respectively. While the neuronal components to detect these physical attributes are similar between the two sensory systems, the organizational pattern of the receptors in the periphery and the distribution of hindbrain afferent and efferent projections are adapted to the specific functions of the respective system. Here we provide a concise review comparing the functional organization of the vestibular and lateral line systems from the development of the organs to the wiring from the periphery and the first processing stages. The goal of this review is to highlight the similarities and differences to demonstrate how evolution caused a common neuronal substrate to adapt to different functions, one for the detection of external water stimuli and the generation of sensory maps and the other for the detection of self-motion and the generation of motor commands for immediate behavioral reactions. PMID- 28988235 TI - Readmissions and Emergency Department Visits after Bariatric Surgery at Saudi Arabian Hospital: The Rates, Reasons, and Risk Factors. AB - BACKGROUND: Saudi Arabian hospital readmissions and emergency department (ED) visits following bariatric surgery and discharge have never been investigated. This study aimed to evaluate the rates and reasons of hospital readmissions and ED visits related to surgical weight loss interventions at the King Abdulaziz Medical City - Riyadh. METHODS: We conducted a retrospective cohort study on 301 patients who underwent bariatric surgery between January 2011 and July 2016. We reviewed patient medical records progressively to assess hospital readmission, ED visits, and complications. RESULTS: Of the 301 patients analyzed, 67.1% were female and 93% had class II obesity. The readmission rate, ED visit rate after discharge and the rate of either of the two was 8%, 14%,and 18.3%, respectively. The most common causes of readmission were abdominal pain (37.5%), nausea/vomiting (29.2%), and site leak (25%), while the most common causes of ED visits were abdominal pain (59.5%) and nausea/vomiting (16.9%). Readmission rates tended to be higher in older patients (age of patients readmitted 42 +/- 12.1 years vs. age of patients not readmitted 34.3 +/- 11.8 years; p = 0.002). The rate of readmission tends to increase in patients with overweight or class I obesity (odds ratio (OR) = 20.15), diabetes (OR = 14.82), and obstructive sleep apnea (OR = 14.29). Dyslipidemia was positively associated with ED visits (p = 0.027, OR = 2.87). The rate of readmission or ED visits increased with age, while there were decreases in readmission and ED visits for those who had received gastric sleeve surgery. CONCLUSIONS: The study reported high rates of readmission and ED visits, thus the effectiveness of different types of weight loss surgeries should be further evaluated, particularly in individuals with complicated medical issues such as diabetes, dyslipidemia, and obstructive sleep apnea. PMID- 28988238 TI - Bo Sun and the Development of Neonatology in China. PMID- 28988239 TI - Extended Abstracts: VIIIth Recent Advances in Neonatal Medicine. An International Symposium Honoring Prof. Bo Sun. Wurzburg, October 8-10, 2017. PMID- 28988241 TI - Macrophage Extracellular Traps: A Scoping Review. AB - Tissue macrophages are derived from either circulating blood monocytes that originate in the bone marrow, or embryonic precursors that establish residence in tissues and are maintained independent of bone marrow progenitors. Macrophages perform diverse functions including tissue repair, the maintenance of homeostasis, and immune regulation. Recent studies have demonstrated that macrophages produce extracellular traps (ETs). ETs are an immune response by which a cell undergoes "ETosis" to release net-like material, with strands composed of cellular DNA that is studded with histones and cellular proteins. ETs are thought to immobilize and kill microorganisms, but also been implicated in disease pathology including aseptic inflammation and autoimmune disease. We conducted a scoping review to define what is known from the existing literature about the ETs produced by monocytes or macrophages. The results suggest that macrophage ETs (METs) are produced in response to various microorganisms and have similar features to neutrophil ETs (NETs), in that METs are produced by a unique cell death program (METosis), which results in release of fibers composed of DNA and studded with cellular proteins. METs function to immobilize and kill some microorganisms, but may also play a role in disease pathology. PMID- 28988240 TI - Economic Evaluation of Intensive Inpatient Treatments for Severely Obese Children and Adolescents. AB - BACKGROUND: Considering the large economic consequences of severe childhood obesity for the society, we aimed to conduct an economic evaluation comparing two intensive 1-year lifestyle treatments with varying inpatient periods for severely obese children and adolescents with regard to standard deviation score BMI (SDS BMI) and quality-adjusted life years (QALYs). METHODS: An economic evaluation from a societal perspective accompanying a randomized controlled trial with a 24 month follow-up. 80 participants (8-19 years) with severe obesity were included. Participants received an intensive 1-year lifestyle treatment with an inpatient period of 2 months (short-stay group) or 6 months (long-stay group). Data were collected at baseline, 6, 12 ,and 24 months and included SDS-BMI and QALYs. RESULTS: SDS-BMI decreased in the first 6 months of treatment, stabilized in the second 6 months, and increased during the 2nd year in both groups. After 24 months, SDS-BMI was similar in both groups, but remained lower than baseline values (mean difference -0.24, 95% CI -0.42; -0.06). There was no difference in QALYs between the groups after 24 months. For SDS-BMI, the probability of the short-stay treatment being cost-effective in comparison with the long-stay treatment was 1 at a willingness-to-pay of 0 EUR/unit of effect, which slowly decreased to 0.54 for larger willingness-to-pay values. CONCLUSIONS: Based on the results of this study, the short-stay treatment is considered to be more cost effective from the societal perspective in comparison with the long-stay treatment. Future research should provide insight in whether the short-stay treatment is cost-effective in comparison with usual care. PMID- 28988242 TI - Names Matter: Commentary on Luis Puelles' Article. PMID- 28988243 TI - Efficacy in Treating Lung Metastasis of Invasive Breast Cancer with Functional Vincristine Plus Dasatinib Liposomes. AB - BACKGROUND: The metastasis of breast cancer is the leading cause of death, while lung metastasis is a major clinical phenomenon in patients with invasive breast cancer. The current treatment option comprising surgery, radiation, and standard chemotherapy cannot achieve a satisfactory effect on the treatment of lung metastasis of breast cancer. In this study, we report the potential of preventing lung metastasis of invasive breast cancer using the newly developed functional vincristine plus dasatinib liposomes. METHODS: The investigations were performed on invasive breast cancer MDA-MB-231 cells in vitro and in lung metastatic model of invasive breast cancer MDA-MB-231 cells in nude mice. RESULTS: The functional drug liposomes were able to induce cell cycle arrest at G2/M phase, induce apoptosis, inhibit adhesion, migration, and invasion of breast cancer cells in vitro, and prevent lung metastasis of breast cancer in nude mice. CONCLUSION: These findings indicate a potential clinical use of functional vincristine plus dasatinib liposomes for treating metastatic breast cancer. PMID- 28988245 TI - Basic in vitro Characterization of the Vasodilatory Potential of 2-Aminoethyl Nitrate Fixed-Dose Combinations with Cilostazol, Metoprolol and Valsartan. AB - BACKGROUND/AIMS: 2-aminoethyl nitrate (CLC-1011) is a member of the class of organic nitrates that cause vasodilation by the generation of nitric oxide (*NO). These drugs are mainly used for the treatment of angina pectoris and ischemic heart disease. The aim of this study was to characterize the vasodilatory potency of this organic nitrate alone and in combination with clinically established cardiovascular drugs. METHODS: Vasodilation by CLC-1011 was tested by isometric tension studies, either alone or combined with cilostazol, valsartan, and metoprolol. Induction of oxidative stress in isolated heart mitochondria was measured by enhanced chemiluminescence. Bioactivation of CLC-1011 in aortic tissue was measured by electron paramagnetic resonance spectroscopy using an iron based spin trap for *NO. RESULTS: We observed potent vasodilation by CLC-1011 and additive effects for all three drug combinations. In contrast to nitroglycerin (GTN), CLC-1011 did not stimulate mitochondrial oxidative stress. CLC-1011 was bioactivated to *NO in aortic tissue. CONCLUSION: In summary, the experiments described in this report demonstrate that CLC-1011 does not induce oxidative stress, is a more potent vasodilator than isosorbide-5-mononitrate and dinitrate ISDN, and displays synergistic vasodilation with other cardiovascular drugs. CLC 1011 fixed dose combinations could be used in the management of cardiovascular diseases. PMID- 28988244 TI - Evolution of Sound Source Localization Circuits in the Nonmammalian Vertebrate Brainstem. AB - The earliest vertebrate ears likely subserved a gravistatic function for orientation in the aquatic environment. However, in addition to detecting acceleration created by the animal's own movements, the otolithic end organs that detect linear acceleration would have responded to particle movement created by external sources. The potential to identify and localize these external sources may have been a major selection force in the evolution of the early vertebrate ear and in the processing of sound in the central nervous system. The intrinsic physiological polarization of sensory hair cells on the otolith organs confers sensitivity to the direction of stimulation, including the direction of particle motion at auditory frequencies. In extant fishes, afferents from otolithic end organs encode the axis of particle motion, which is conveyed to the dorsal regions of first-order octaval nuclei. This directional information is further enhanced by bilateral computations in the medulla and the auditory midbrain. We propose that similar direction-sensitive neurons were present in the early aquatic tetrapods and that selection for sound localization in air acted upon preexisting brain stem circuits like those in fishes. With movement onto land, the early tetrapods may have retained some sensitivity to particle motion, transduced by bone conduction, and later acquired new auditory papillae and tympanic hearing. Tympanic hearing arose in parallel within each of the major tetrapod lineages and would have led to increased sensitivity to a broader frequency range and to modification of the preexisting circuitry for sound source localization. PMID- 28988246 TI - Comments on the Updated Tetrapartite Pallium Model in the Mouse and Chick, Featuring a Homologous Claustro-Insular Complex. AB - This essay reviews step by step the conceptual changes of the updated tetrapartite pallium model from its tripartite and early tetrapartite antecedents. The crucial observations in mouse material are explained first in the context of assumptions, tentative interpretations, and literature data. Errors and the solutions offered to resolve them are made explicit. Next, attention is centered on the lateral pallium sector of the updated model, whose definition is novel in incorporating a claustro-insular complex distinct from both olfactory centers (ventral pallium) and the isocortex (dorsal pallium). The general validity of the model is postulated at least for tetrapods. Genoarchitectonic studies performed to check the presence of a claustro-insular field homolog in the avian brain are reviewed next. These studies have indeed revealed the existence of such a complex in the avian mesopallium (though stratified outside-in rather than inside-out as in mammals), and there are indications that the same pattern may be found in reptiles as well. Peculiar pallio-pallial tangential migratory phenomena are apparently shared as well between mice and chicks. The issue of whether the avian mesopallium has connections that are similar to the known connections of the mammalian claustro insular complex is considered next. Accrued data are consistent with similar connections for the avian insula homolog, but they are judged to be insufficient to reach definitive conclusions about the avian claustrum. An aside discusses that conserved connections are not a necessary feature of field-homologous neural centers. Finally, the present scenario on the evolution of the pallium of sauropsids and mammals is briefly visited, as highlighted by the updated tetrapartite model and present results. PMID- 28988247 TI - Distinct Penetrance of Obesity-Associated Susceptibility Alleles in the Hungarian General and Roma Populations. AB - AIMS: The aim of our study was to explore differences in genetic predisposition to obesity between the Hungarian general and Roma populations. METHODS: A total of 1,152 samples from the Hungarian Roma population and 1,743 samples from the Hungarian general population were genotyped for 20 single nucleotide polymorphisms (SNPs) associated with the risk of obesity. Two types of multilocus genetic risk scores were constructed to estimate the combined effect of selected SNPs. RESULTS: Risk allele frequencies differed significantly between the two populations for 11 SNPs, with no enrichment in any of the two study groups. Variants (rs1558902, rs1121980, rs9939609, and rs9941349) in the fat mass and obesity-associated (FTO) gene exhibited strong but ethnicity-independent association with obesity. Genetic risk scores showed stronger associations with obesity in the Roma population compared with the Hungarian general population; however, without significant gene-population interaction. CONCLUSION: Differences in obesity prevalence between the Hungarian general and Hungarian Roma populations could not be explained by their distinct genetic susceptibility, rather by ethnicity-related environmental and behavioral factors. Nonetheless, particular gene-environment interactions might contribute to the distinct penetrance of the obesity-associated genetic factors in populations of different ethnic backgrounds. PMID- 28988249 TI - Validation of the Arabic version of the score for allergic rhinitis tool. AB - BACKGROUND: Allergic rhinitis (AR) is a common inflammation of the nasal mucosa in response to allergen exposure. We translated and validated the Score for Allergic Rhinitis (SFAR) into an Arabic version so that the disease can be studied in an Arabic population. OBJECTIVES: SFAR is a non-invasive self administered tool that evaluates eight items related to AR. This study aimed to translate and culturally adapt the SFAR questionnaire into Arabic, and assess the validity, consistency, and reliability of the translated version in an Arabic speaking population of patients with suspected AR. STUDY DESIGN: Cross-sectional. SETTING: Tertiary care hospital in Riyadh. PARTICIPANTS AND METHODS: The Arabic version of the SFAR was administered to patients with suspected AR and control participants. MAIN OUTCOME MEASURE: Comparison of the AR and control groups to determine the test-retest reliability and internal consistency of the instrument. RESULTS: The AR (n=173) and control (n=75) groups had significantly different Arabic SFAR scores (P < .0001). The instrument provided satisfactory internal consistency (Cronbach's alpha value of 0.7). The test-retest reliability was excellent for the total Arabic SFAR score (r =0.836, P < .0001). CONCLUSION: These findings demonstrate that the Arabic version of the SFAR is a valid tool that can be used to screen Arabic speakers with suspected AR. LIMITATIONS: The absence of objective allergy testing. PMID- 28988248 TI - Risk of pneumonia among patients with splenectomy: a retrospective population based cohort study. AB - BACKGROUND: People without a spleen are particularly susceptible to various overwhelming infections including pneumonia. Although the association between splenectomy and pneumonia has been previously studied, there has been no study using the national claims data. OBJECTIVES: The aim of the study was to investigate the association between splenectomy and pneumonia. DESIGN: A retrospective population-based cohort analysis. SETTINGS: Database of the Taiwan National Health Insurance Program. PATIENTS: Persons newly diagnosed with splenectomy from 2000 to 2010 were compared with randomly selected subjects without splenectomy. The groups were matched by sex, age, comorbidities, and the year of index date and analyzed by multivariate methods. MAIN OUTCOME MEASURE: The difference in incidence of pneumonia at the end of 2011. RESULTS: In 12 757 individuals aged 20-84 years with splenectomy, the overall incidence of pneumonia was 1.86-fold higher than in the 51 019 individuals without splenectomy (25.0 vs. 13.4 per 1000 person-years, 95% CI 1.78, 1.95). After multivariate analysis, the adjusted hazard ratio for pneumonia was 2.2 for subjects with splenectomy (95%CI 2.07, 2.34). In further analysis, in the absence of any comorbidity, the adjusted HR for pneumonia was 3.03 for those with splenectomy alone (95% CI 2.76, 3.33) and 5.28 (95% CI 4.82, 5.78) for splenectomy and any comorbidity. CONCLUSIONS: Although not a novel finding, we confirmed that splenectomy increases the relative risk for developing pneumonia in a large study population. Even in the absence of any comorbidity, the risk remains high. Patients with splenectomy should receive preventive interventions for pneumonia, such as vaccination. LIMITATIONS: ICD-9 codes do not differentiate if pneumonia is caused by a viral, a bacterial or unspecified organisms, and some behavioral factors like smoking could not be ascertained directly. PMID- 28988250 TI - Prevalence of glucose-6-phosphate dehydrogenase deficiency in neonates in Egypt. AB - BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked disorder which causes neonatal jaundice in most cases, and under certain conditions, can cause a spectrum of hemolytic manifestations. OBJECTIVE: To determine the local prevalence of G6PD deficiency in newborns. DESIGN: Cross sectional. SETTING: University hospital. METHODS: Infants born during 2015 were prospectively screened for G6PD deficiency. Dried blood spot samples on filter paper were collected in collaboration with the central laboratories of the Ministry of Health. Quantitative measurement of G6PD enzyme activity was measured from the blood samples using fluorometric analysis. A value. PMID- 28988251 TI - Efficacy and safety of a generic rosuvastatin in a real-world setting: prospective, observational clinical study in Lebanese patients. AB - BACKGROUND: No published studies have assessed the efficacy and safety of rosuvastatin generics. OBJECTIVES: Primary objective to assess the safety and efficacy of a generic rosuvastatin in reducing plasma low-density-lipoprotein cholesterol (LDL-C) in Lebanese dyslipidemic patients. Changes in high-density lipoprotein cholesterol, triglycerides and adverse effects were secondary objectives. DESIGN: Prospective, observational, non-comparative. SETTING: Multiple outpatient clinics in Lebanon. PATIENTS AND METHODS: Dyslipidemic patients requiring statin therapy were followed for 2 months after prescription of a generic rosuvastatin at the physician's discretion. Efficacy and safety measurements were collected from medical records. MAIN OUTCOME MEASURES: Efficacy was assessed based on the evaluation of mean and percent change in LDL-C between baseline and week 8 as well as the proportion of patients reaching target LDL-C levels. Safety was assessed based on the evaluation of the incidence of adverse events (AEs) during the study period. RESULTS: Two months after initiation of generic rosuvastatin, LDL-C levels in the 313 eligible patients who completed the study significantly decreased from 4.3 (0.8) mmol/L (168.2 [31.3] mg/dL) at baseline to 2.7 (0.7) mmol/L (105.9 [25.5] mg/dL) (P < .001). The mean percent change in LDL-C level was highest in subjects receiving generic rosuvastatin at a dose of 40 mg/day (-47.4%), followed by 20 mg/day (-36.8%), and 10 mg/ day ( 31.4%); 82.5% of patients reached the target LDL-C level as set by their physician at baseline. Thirteen patients (4%) reported six AEs during treatment: abdominal pain, headache, stomach ache, insomnia, musculoskeletal pain/myalgia and nausea. No clinically significant changes in serum creatinine, serum creatine kinase, or liver function tests were reported. One patient withdrew because of an adverse event. CONCLUSIONS: Generic rosuvastatin was efficacious and safe in reducing LDL-C levels and helping the majority of patients achieve LDL-C targets after a short treatment period. LIMITATIONS: The observational nature, and a control group, and the relatively short duration of follow-up limit the generalizability of results. The authors received fees for study activities at patient visits from an independent clinical research organization subcontracted by the sponsor. PMID- 28988252 TI - Drug shortages in large hospitals in Riyadh: a cross-sectional study. AB - BACKGROUND: Drug shortages are a serious and complex issue in any healthcare system. We conducted this study because the prevalence of drug shortages in Saudi Arabia is largely unknown, while there have been reports of shortages. OBJECTIVE: To explore the prevalence and characteristics of drug shortages as well as identify strategies to minimize their impact on patient care and safety in large hospitals. DESIGN: Questionnaire-based cross-sectional study. SETTING: Pharmacy departments in secondary and tertiary care hospitals in the city of Riyadh. SUBJECTS AND METHODS: Pharmacists in ten hospitals, categorized as Ministry of Health [MOH], MOH-affiliated medical cities, and non-MOH, were recruited using convenience sampling. The European Association of Hospital Pharmacists drug shortage questionnaire was administered to survey pharmacists about drug shortages in their hospitals. MAIN OUTCOME MEASURES: Percentages of drug class shortages, characteristics, and strategies to minimize impact on patient care and safety across each hospital sector. RESULTS: Of 200 pharmacists invited to participate, 120 pharmacists completed the questionnaire (60% response rate). Twenty-four percent were from MOH hospitals, 32% from MOH-affiliated medical cities, and 44% from non-MOH hospitals. A significantly higher percentage of pharmacists from MOH-affiliated medical cities (42.11%) reported encountering drug shortages on a daily basis compared to 13.79% and 15.09% of participants from MOH-hospitals and non-MOH hospitals, respectively (P=.001). The top three drug classes that >= 25% of participants reported having shortages of were cardiovascular, antineoplastic, and endocrine drugs. The two most common strategies that were reported to minimize the impact of drug shortages on patient care by more than 70% of participants were informing prescribers and recommending alternative drugs, and alerting hospital staff about the presence of drug shortages using new communication tools. CONCLUSIONS: The relatively high reported rates of drug shortages in some hospitals should encourage health policymakers to address this serious public health problem. LIMITATIONS: The generazibility of the study's findings were limited by the small sample size, convenience sampling technique, self-reported data, and the fact that only pharmacists were invited to participate. PMID- 28988253 TI - Prevalence of congenital heart diseases in children with Down syndrome in Mansoura, Egypt: a retrospective descriptive study. AB - BACKGROUND: The pattern and risk factors for congenital heart diseases (CHD) in children with Down syndrome (DS) vary over time. OBJECTIVES: To update knowledge of the prevalence, types, trends and associated factors for CHD in children with DS in the Egyptian Delta. DESIGN: A retrospective hospital record-based descriptive study. SETTING: A tertiary care center in Mansoura, Egypt during a period of 14 years from 2003 up to 2016. PATIENTS AND METHODS: We studied children with genetically proven DS. Relevant sociodemographic factors, medical history, clinical examination, karyotype and echocardiographic data were statistically analyzed. MAIN OUTCOME MEASURES: Prevalence, types and risk factors of CHD in DS. RESULTS: The prevalence of overall, isolated and multiple CHD in 1720 children with DS were 36.9%, 29% and 8%, respectively. Isolated defects accounted for 78.4% of all CHD. Ventricular septal defect, atrioventricular septal defect and atrial septal defect were the most frequent isolated defects. There was a downward trend in the prevalence of overall CHD (from 56.2% to 25.0%) and isolated CHD (from 56.2% to 19.8%). The logistic regression model predicted 65.7% of CHD and revealed that passive maternal smoking, lack of folic acid/multivitamin supplementation and parental consanguinity were the independent predictors of CHD in children with DS with adjusted odds ratios of 1.9, 1.8 and 1.9, respectively. CONCLUSION: More than one-third of children with DS have CHD with ventricular septal defect, which is the most common. Avoidance of passive maternal smoking and consanguineous marriage together with maternal folic acid supplementation could contribute to further reduction of CHD in children with DS. LIMITATIONS: Single-center study and retrospective. PMID- 28988254 TI - Preoperative thrombocytosis as a prognostic factor in endometrioid-type endometrial carcinoma. AB - BACKGROUND: The impact of preoperative thrombocytosis as a prognostic factor in endometrial carcinoma (EC) remains uncertain and has never been examined in Saudi Arabia. OBJECTIVES: To determine the prevalence of preoperative thrombocytosis (platelet count > 400 000/ MUL), and its prognostic significance for clinicopathological factors and survival in Saudi patients with endometrioid-type EC. DESIGN: A retrospective cross-sectional study from January 2010 to December 2013. SETTING: A referral tertiary healthcare institute. PATIENTS AND METHODS: Patients who underwent staging surgery for primary endometrioid-type EC were retrospectively analyzed for perioperative details: age, preoperative platelet count, International Federation of Gynecology and Obstetrics (FIGO) stage, endometrioid grade, recurrence, disease-free survival (DFS) and overall survival (OS). Survival analysis was conducted using Kaplan-Meier estimates and a Cox proportional hazards model. MAIN OUTCOME MEASURES: Prevalence of preoperative thrombocytosis, DFS and OS. RESULTS: In 162 patients who met inclusion criteria, the frequency of preoperative thrombocytosis was 8.6% (n=14). Patients with advanced FIGO disease (stages III-IV) and recurrence had significantly higher mean preoperative platelet counts than patients with early FIGO disease (stages I II) and no recurrence (P=.0080 and P=.0063, respectively). Patients with thrombocytosis had statistically significant higher rates of advanced FIGO stages III-IV disease, unfavorable grades II-III endometrioid histology and recurrence than patients with preoperative platelet counts. PMID- 28988255 TI - Cardiac rhythm recorded by implanted loop recorder during lightning strike. AB - : Lightning strikes cause severe injuries and fatalities. Injuries vary from self limiting skin manifestations to cardiac arrest and death. Because the event is sudden and unpredictable, assessment of the direct effects of the lightning on the human heart is usually impossible. In this case, a 16-year old boy who had an implanted loop recorder subcutaneous cardiac monitor was hit by lightning during a picnic and survived. A cardiac rhythm strip was recorded live during the strike. SIMILAR CASES PUBLISHED: 0. PMID- 28988256 TI - Primary leiomyosarcoma of the atrium with heterologous differentiation. AB - : We report a case of a 47-year-old female who presented with breathlessness and palpitations for two weeks. On clinical evaluation, bilateral pedal edema was noticed. A CT pulmonary angiogram showed a mass in the left atrium causing significant obstruction to cardiovascular outflow. After extensive work-up, the mass was surgically resected. Histopathological findings from the acquired specimen revealed a high-grade leiomyosarcoma with extensive necrosis and heterologous (cartilaginous) differentiation. The early postoperative period was complicated by cardiac tamponade and the patient died on the second postoperative day due to ventricular arrhythmia, shock and multiorgan failure. SIMILAR CASES PUBLISHED: No similar cases published. PMID- 28988257 TI - Clinical and Prognostic Significance of Pathological and Inflammatory Markers in Mucinous Rectal Cancer Patients Receiving Neoadjuvant Chemoradiotherapy and Curative Surgery. AB - BACKGROUND The aim of this study was to investigate the clinical and prognostic significance of pathological and inflammatory marker in mucinous rectal cancer patients receiving neoadjuvant chemoradiotherapy and curative surgery. MATERIAL AND METHODS We retrospectively evaluated the patient records of mucinous rectal cancer patients receiving neoadjuvant chemoradiotherapy and curative surgery at Liaoning Cancer Hospital and Institute from January 2006 to December 2013. The relationship between overall survival (OS) and clinicopathologic variables, pretreatment neutrophil-to-lymphocyte ratio (NLR), pretreatment platelet-to lymphocyte ratio (PLR), pretreatment lymphocyte-to-monocyte ratio (LMR), and other biomarkers were analyzed by using Kaplan-Meier analysis and log-rank testing. Subsequently a Cox proportional hazard model was used to calculate hazard ratios for the risk of death. RESULTS A total of 100 mucinous rectal cancer patients were included for analysis during the study period. The median age at presentation was 60.5 years (range, 26-81 years). The median overall survival (OS) for the whole group was 94 months. On univariate analysis, time interval from CCRT to operation (HR 0.37, p=0.03), lymphovascular invasion (HR 3.23, p=0.009), pretreatment NLR (HR 3.87, p=0.012), and LMR (HR 0.31, p=0.002) were significant prognostic factors for OS. In a multivariate analysis, pretreatment LMR was found to be an independent prognostic factor for overall survival (HR, 0.43; 95%CI, 0.18 to 1.00, p=0.045). CONCLUSIONS Pretreatment lymphocyte-to-monocyte ratio is a useful prognostic marker of OS in patients with mucinous rectal carcinoma treated with neoadjuvant chemoradiotherapy and curative surgery. PMID- 28988258 TI - Moving beyond descriptions of diversity: clinical and research implications of bacterial imbalance in chronic rhinosinusitis. AB - Chronic rhinosinusitis (CRS) is a debilitating disease which affects 5-16% of the general population and involves long-term inflammation of the sinonasal cavity. While microbial involvement in the pathogenesis of CRS has long been suspected, the exact role of microbes remains unclear. Recent application of cultivation independent, molecular methods has provided much new information, taking advantage of developments in both laboratory- and bioinformatics-based analyses. The aim of this mini-review is to present a variety of available bioinformatics approaches, such as data classification techniques and network analyses, with proven applications in other aspects of human microbiome health and disease research. The uses of molecular techniques in the clinical setting are still in its infancy, but these tools can further our understanding of microbial imbalance during chronic disease and help guide effective patient treatment. The mini review emphasises ways in which CRS bacterial gene-targeted sequencing data can progress beyond descriptive summaries and toward unlocking the mechanisms by which bacterial communities can be markers for sinus health. PMID- 28988259 TI - A straight choice: avoiding septal re-deviation using titanium plates. A 16 year retrospective patient follow-up evaluation. AB - BACKGROUND: To propose a new surgical technique for fixing the nasal septum to the midline, for long term prevention of nasal obstruction, in secondary and select cases of primary septoplasty. METHODOLOGY: Retrospective study, within hospital medical center. PATIENTS: Two hundred and twenty two patients who underwent septoplasty. Data collection occurred consecutively between March 1st of 2000 and May 1st 2016. Twenty six percent females and seventy four percent males. MAIN OUTCOME MEASURES: Patterns of septal deformity, materials used for titanium plates, surgical results, symptom improvement, and surgical complications were investigated. RESULTS: A total of 222 patients were included in this study. 163 patients (73%) had no previous nasal surgery. Fifty nine patients (27%) presented with a previous nasal surgery. Sixteen year follow up included more than 90% of patients and resulted in an overall 2.7% revision rate. CONCLUSIONS: The use of titanium plate for septoplasty has shown to be simple, safe, and easy to learn technique in both secondary and select cases of primary septoplasty. Most importantly the results indicate a long term prevention of the. PMID- 28988260 TI - The significance of Computed Tomography in invasive paranasal mucormycosis. AB - INTRODUCTION: Early diagnosis of acute invasive fungal rhinosinusitis (AIFR) is crucial for patients prognosis and may reduce the extent of surgical debridement. Initial evaluation usually includes paranasal Computed Tomography (CT), with an emphasis on bony erosion which is considered a specific but insensitive radiologic sign. Most studies made no distinction between Aspergillus and Mucor species while addressing CT findings. In this study, we seek to evaluate whether bony erosion on paranasal CT is a significant and reliable finding in the initial evaluation of invasive paranasal mucormycosis. METHODS: A retrospective review of pre-operative non-contrast craniofacial CT scans of patients diagnosed with acute invasive fungal rhinosinusitis (AIFR) caused by Mucor species for the presence of bony erosion. RESULTS: A total of 13 patients (9 males, 4 females) were included. Twelve patients were immunosuppressed due to various hematological malignancies. Six patients underwent debridement due to gross intraoperative findings of bony fungal invasion, but only one patient had evidence of bony erosion on the pre operative paranasal CT. CONCLUSION: Bony erosion on paranasal CT is an exceptionally insensitive radiologic sign for establishing or rejecting the diagnosis of Mucor induced AIFR. The mainstay of confirming or rejecting the diagnosis of AIFR is by physical examination, endoscopy and oriented biopsy of suspicious mucosal lesions. PMID- 28988261 TI - The Sickness of Stigmas. AB - In modern medicine, approaches to healthcare no longer only encompass injury management, but increasingly focus on understanding the performance demands and health risk exposures faced by performing artists. Quantitative and qualitative scientific and health analyses by performing artists, clinicians, educators, and researchers are increasingly helping us to develop effective, targeted, and relevant health promotion and performance optimisation strategies worldwide. While such research increasingly identifies improved methods of preventing and managing potential psychological, audiological, or physical challenges faced by performing artists, we still need to work hard to address very important barriers to implementing appropriate health approaches. One of the challenges to better health management in performing arts populations relates to stigmatization. PMID- 28988262 TI - Playing the Clarinet: Influence of Body Posture on Muscle Activity and Sound Quality. AB - Musculoskeletal complaints are highly prevalent in clarinetists and are related to high arm load while playing. It is hypothesized that postural exercise therapy may be used to adapt muscle activity patterns while playing and thus contribute to better sound quality. The goal of the present study was to investigate the relationship between body posture, muscle activity, and sound quality in clarinetists while playing the instrument in two different postures, their habitual sitting posture (control, CO) vs an experimental sitting posture (EXP) based on Mensendieck postural exercise therapy, method Samama. Twenty healthy professional and student clarinet players, aged 18-60 years, were included in this cross-sectional study. Participants played a 60-second musical excerpt in CO, followed by instruction on the EXP body posture, and then played in the EXP condition. Two-dimensional goniometric analysis was used to calculate body posture; muscle activity was measured bilaterally using surface electromyography. In EXP, a significantly smaller low thoracic angle, smaller high thoracic angle, and larger pelvic tilt angle (all p<0.001) were found. EMG results indicated that the left and right erector spinae L3 and left and right lower trapezius were more active in EXP compared to CO, whereas left upper trapezius and right brachioradialis were less active in EXP than CO. Most participants experienced better sound quality in EXP, whereas blinded experts found no consistent pattern between body posture and sound quality. To conclude, it seems that postural exercise therapy may change muscle activity patterns. By increasing stability, a decrease in activity of the upper extremity muscles can be induced. PMID- 28988263 TI - Reducing Risk of Noise-Induced Hearing Loss in Collegiate Music Ensembles Using Ambient Technology. AB - Student musicians are at risk for noise-induced hearing loss (NIHL) as they develop skills and perform during instructional activities. Studies using longitudinal dosimeter data show that pedagogical procedures and instructor behaviors are highly predictive of NIHL risk, thus implying the need for innovative approaches to increase instructor competency in managing instructional activities without interfering with artistic and academic freedom. Ambient information systems, an emerging trend in human-computer interaction that infuses psychological behavioral theories into technologies, can help construct informative risk-regulating systems. The purpose of this study was to determine the effects of introducing an ambient information system into the ensemble setting. The system used two ambient displays and a counterbalanced within subjects treatment study design with six jazz ensemble instructors to determine if the system could induce a behavior change that alters trends in measures resulting from dosimeter data. This study assessed efficacy using time series analysis to determine changes in eight statistical measures of behavior over a 9 wk period. Analysis showed that the system was effective, as all instructors showed changes in a combination of measures. This study is in an important step in developing non-interfering technology to reduce NIHL among academic musicians. PMID- 28988264 TI - Analysis of High-Density Surface EMG and Finger Pressure in the Left Forearm of Violin Players: A Feasibility Study. AB - Wrist and finger flexor muscles of the left hand were evaluated using high density surface EMG (HDsEMG) in 17 violin players. Pressure sensors also were mounted below the second string of the violin to evaluate, simultaneously, finger pressure. Electrode grid size was 110x70 mm (12x8 electrodes with interelectrode distance=10 mm and O=3 mm). The study objective was to observe the activation patterns of these muscles while the violinists sequentially played four notes--SI (B), DO# (C#), RE (D), MI (E)--at 2 bows/s (one bow up in 0.5 s and one down in 0.5 s) and 4 bows/s on the second string, while producing a constant (CONST) or ramp (RAMP) sound volume. HDsEMG images obtained while playing the notes were compared with those obtained during isometric radial or ulnar flexion of the wrist or fingers. Two image descriptors provided information on image differences. Results showed that the technique was reliable and provided reliable signals, and that recognizably different sEMG images could be associated with the four notes tested, despite the variability within and between subjects playing the same note. sEMG activity of the left hand muscles and pressure on the string in the RAMP task were strongly affected in some individuals by the sound volume (controlled by the right hand) and much less in other individuals. These findings question whether there is an individual or generally optimal way of pressing violin strings with the left hand. The answer to this question might substantially modify the teaching of string instruments. PMID- 28988266 TI - Effect of Arm Position on Width of the Subacromial Space of Upper String Musicians. AB - OBJECTIVE: Musicians often end their musical career due to musculoskeletal injury. A leading source of shoulder pain in upper string musicians is rotator cuff disease (RCD). Multiple factors contribute to its development. Compressive overload of the soft tissues of the subacromial space resulting from a decrease in the width of the subacromial space has been identified as an extrinsic factor contributing to RCD development. The purpose of this study was to characterize the width of the subacromial space by measuring acromial-humeral distance (AHD) of upper string musicians, while their arms are in standard playing positions. METHODS: Experienced musicians (n=23) were recruited from local communities. Shoulder ultrasound images were collected using standard imaging techniques. Images were collected and the AHD measured while the musician's arm was in positions associated with playing the violin. RESULTS: On the right side, the arm position main effect was significant (p<0.001): the AHD in the 4th string position (8.8+/-1.9 mm) was less than the 1st string (11.3+/-1.4 mm) and resting (11.7+/-1.3 mm) positions. There was no difference in AHD between resting (10.0+/ 5.8 mm) and instrument-support positions (10.6+/-1.5 mm). The resting AHD was smaller (p=0.04) on the right side compared to the left (12.2+/-1.4 mm). There was not statistically significant difference (p=0.138) in the occupation ratio (supraspinatus tendon thickness/AHD) between the right (mean 0.543+/-0.80 mm) and left sides (mean 0.510+/-0.087 mm). CONCLUSIONS: The AHD measurement decreased in the playing positions compared to resting positions. Treatment interventions that help musicians maximize the width of their subacromial space might help reduce the prevalence of shoulder pain in this population. PMID- 28988265 TI - Overuse Injuries in Professional Anatolian Folk Dancers: A Descriptive Study Verified with MRI. AB - BACKGROUND: Professional dancers are artists as well as athletes who push their bodies beyond limits for aesthetic expression. Therefore, overuse injuries are common. We present our findings on overuse injuries in Anatolian (Turkish) folk dancers. METHODS: The Fire of Anatolia dance group comprises of 82 dancers (37 male, 45 female) with a mean age of 27.96+/-5.05 yrs (range 18 to 38). Forty-one dancers from this group presented to our clinic between February 2009 and April 2016 with complaints of pain, and 25 of them had magnetic resonance imaging (MRI) for verification. The type, frequency, and anatomical locations of their overuse injuries as found on MRI were investigated. RESULTS: We evaluated a total of 70 overuse injuries in 25 dancers. All injuries were seen on separate occasions, and multiple injuries in the same dancers at separate times were recorded. Most of the overuse injuries were seen around the knee joint. Ankle ligament injuries were not seen in our study, in contrast to ballet and modern dance. Overuse injuries were observed in the knee in 68% of cases, thigh in 24%, lumbar region in 24%, feet in 20%, shoulder in 16%, and hip in 12%. CONCLUSIONS: Overuse injuries occur mostly in the knee region in Anatolian folk dancers. There were no statistically significant differences between dancers with and without overuse injuries in terms of age, sex, and dance style (p>0.05). PMID- 28988267 TI - Leg-Length in Relation to Selected Ballet Performance Indicators. AB - : It is unclear whether the modern ballet body stereotype of long limbs is advantageous in dance performance. Therefore, we investigated the relationship between leg-length and selected dance movements representative of power, dexterity, and range of motion in ballet dancers at different competence levels. METHODS: The total of 10 recreational, 24 vocational, and 10 professional ballerinas volunteered. They were subjected to: a) lower limb-length measurements, b) power tests (vertical jump-sautes and unilateral countermovement jump-temps leve), c) dexterity tests (tendus and double battement frappes), and d) flexibility tests (lateral active and passive-developpe a la seconde). RESULTS: For power, regression analyses revealed negative leg-length relationships in recreational dancers (p<0.05) and positive leg-length relationships in vocational dancers (p<0.05). We also found negative relationships between leg-length and dexterity in the vocational group (p=0.01). No significant predictions of leg-length on power, dexterity, and range of motion were found in professional dancers. Multiple comparisons revealed significant differences between groups only for dexterity (p<0.01) and range of motion (p<0.01). CONCLUSION: Based on selected movements representative of power, dexterity, and range of motion, the present exploratory data indicate that lower limb length is not a determinative criterion for ballet success. Further studies should investigate whether body stereotypes, such as long limbs, are linked to dance injuries. PMID- 28988268 TI - Epidemiology of Dance-Related Injuries Presenting to Emergency Departments in the United States, 2000-2013. AB - : Dance is a popular activity associated with many physical and mental health benefits, but injuries are a concern for all skill levels. Previous studies have focused on professional dancers or particular genres, meaning the population-wide characteristics of injuries is unknown. This study's objective was to identify the incidence and types of dance-related injuries evaluated in emergency departments in the United States over the 14-year period 2000-2013. METHODS: Data were obtained from the nationally representative National Electronic Injury Surveillance System from 2000-2013. National estimates of injuries were determined using complex sample design. Trends using 2-year intervals were calculated using linear regression and injury proportion ratios using Pearson's X2. RESULTS: The average annual incidence of dance-related injuries requiring emergency medical attention was 17,145 per year. The number of injuries grew from 14,204 in 2000/1 to 21,356 in 2012/3, a change of 33.4% after accounting for population growth. Lower limb injuries were most common, particularly ankle and knee sprains. Females presented with a greater proportion of ankle (injury proportion ratio [IPR]=1.34, p=0.029) and foot sprains (IPR=2.11, p<0.001) but a lower proportion of shoulder sprains (IPR=0.41, p<0.001) and face lacerations (IPR=0.13, p<0.001). Younger dancers presented with a lower proportion of knee (IPR=0.79, p=0.006) and low back sprains (IPR=0.68, p=0.019). CONCLUSIONS: The average annual incidence of dance-related injuries of a serious enough nature to require presentation to the emergency department in the United States was 17,145 per year, with ankle and knee sprains being the most common. Injury numbers have increased in recent years. PMID- 28988269 TI - Analysis of Anteroposterior Spinal Curvatures in Child Violinists from Music Schools. AB - : Young musicians often report problems with their upper limbs and spine due to their specific and asymmetric positions and actions while playing, which may contribute to overloading these structures. Diagnosing any disorders to the upper limbs or spine early may help to minimize the risk of developing any serious instrument-related health problems in the future. The aim of this study was to assess the anteroposterior (AP) spinal curvatures in children learning to play the violin. Previous studies have shown anthropomorphic differences in young adult musicians, and our study examined if these differences appeared early or late in the musician's career. METHODS: Body posture of 101 children, aged 7-12 yrs (mean 11.09+/-1.48), was assessed. The study population consisted of 49 child violinists and a control group of 52 children who did not play any musical instrument. There were 81.19% girls and 18.81% boys. Body posture was analyzed using the MORA 4G. RESULTS: The violinist group showed significant differences in the thoracolumbar region angle (p=0.004) compared to the non-musical children. The remaining parameters did not reveal significant differences between groups. The parameter characterizing the location of kyphosis peak calculated from the spinous process of the C7 vertebra was significantly higher in the study population. CONCLUSIONS: Changes in body posture in children who play the violin appear early in their training. Body postures when playing the violin lead to some changes in parameters characterizing AP spinal curvatures in the sagittal plane. PMID- 28988270 TI - Musculoskeletal Problems in Performers. PMID- 28988271 TI - Bridging the gap from prenatal karyotyping to whole-genome array comparative genomic hybridization in Hong Kong: survey on knowledge and acceptance of health care providers and pregnant women. AB - PURPOSE: The use of array comparative genomic hybridization (aCGH) has been increasingly widespread. The challenge of integration of this technology into prenatal diagnosis was the interpretation of results and communicating findings of unclear clinical significance. This study assesses the knowledge and acceptance of prenatal aCGH in Hong Kong obstetricians and pregnant women. The aim is to identify the needs and gaps before implementing the replacement of karyotyping with aCGH. Questionnaires with aCGH information in the form of pamphlets were sent by post to obstetrics and gynecology doctors. METHOD: For the pregnant women group, a video presentation, pamphlets on aCGH and a self administered questionnaire were provided at the antenatal clinic. RESULT: The perception of aCGH between doctors and pregnant women was similar. Doctors not choosing aCGH were more concerned about the difficulty in counseling of variants of unknown significance and adult-onset disease in pregnant women, whereas pregnant women not choosing aCGH were more concerned about the increased waiting time leading to increased anxiety. Prenatal aCGH is perceived as a better test by both doctors and patients. CONCLUSION: Counseling support, training, and better understanding and communication of findings of unclear clinical significance are necessary to improve doctor-patient experience. PMID- 28988272 TI - Pre-culture in endothelial growth medium enhances the angiogenic properties of adipose-derived stem/stromal cells. AB - Considerable progress has been made on the development of adipose-derived stem/stromal cells (ASCs) as pro-angiogenic therapeutic tools. However, variable clinical results highlight the need for devising strategies to enhance their therapeutic efficacy. Since ASCs proliferate and stabilize newly formed vessels during the angiogenic phase of adipose tissue formation, we hypothesized that mimicking an angiogenic milieu during culture of ASCs would enhance their capacity to support endothelial cell survival and angiogenesis. To test this, we compared the effect of an endothelial growth medium (EGM-2) and conventional media (alphaMEM) on the progenitor and angiogenic properties of ASCs. ASCs cultured in EGM-2 (ASC-EGM) displayed the highest clonogenic efficiency, proliferative potential and multilineage potential. After co-culture under growth factor starvation, only ASC-EGM attenuated luciferase-expressing human umbilical vein endothelial cells (HUVECluc) apoptosis and supported the formation of endothelial cords in a dose-dependent manner. These effects were recapitulated by the conditioned medium of ASC-EGM, which displayed a 100-fold higher expression of hepatocyte growth factor in comparison with ASC-alphaMEM. Next, HUVECluc and ASCs were co-transplanted subcutaneously into immunodeficient mice, and the survival of HUVECluc was monitored by bioluminescent imaging. After 60 days, the survival of HUVECluc transplanted alone was equivalent to that of HUVECluc co transplanted with ASC-alphaMEM (15.0 +/- 0.7 vs. 13.0 +/- 0.5%). Strikingly, co transplantation with ASC-EGM increased HUVECluc survival to 105.0 +/- 3.5%, and the resulting organoids displayed functional vasculature with the highest human derived vascular area. These findings demonstrate that pre-conditioning of ASCs in endothelial growth medium augment their pro-angiogenic properties and could enhance their therapeutic efficacy against ischemic diseases. PMID- 28988274 TI - Ultrasound or MR elastography of liver: which one shall I use? AB - Liver stiffness is now a well-established noninvasive biomarker for assessing fibrosis in chronic liver disease. MRI-based and ultrasound-based dynamic elastography techniques have been introduced for assessment of liver stiffness and useful in clinical staging of hepatic fibrosis. Several different elastography techniques are now available with each method having inherent strengths and limitations. The published literature generally indicates that MR elastography has a higher diagnostic performance and fewer technical failures than ultrasound-based elastography techniques in assessing hepatic fibrosis. There is also significant potential to further develop elastography techniques to implement multiparametric methods that have promise for distinguishing between processes such as inflammation, fibrosis, venous congestion, and portal hypertension that can result in increased liver stiffness. In this commentary, we compare MR and ultrasound elastography methods and their utility in clinical practice. PMID- 28988273 TI - Responses of growth, malformation, and thyroid hormone-dependent genes expression in Bufo gargarizans embryos following chronic exposure to Pb2. AB - The aim of this study was to examine the adverse effects of lead (Pb) exposure on Bufo gargarizans embryos. The 96 h-LC50 of Pb2+ for B. gargarizans embryos was determined to be 26.6 mg L-1 after an acute test. In the chronic test, B. gargarizans embryos at Gosner stage 3 were exposed to 10~2000 MUg Pb2+ L-1 during embryogenesis. Total length, weight, developmental stage, and malformation were monitored. In addition, the transcript levels of type II and type III iodothyronine deiodinase (Dio2 and Dio3) and thyroid hormone receptors (TRalpha and TRbeta) were determined to assess the thyroid-disrupting effects of Pb2+. Slightly increased growth and development of B. gargarizans embryos were observed at low concentrations of Pb2+ (10, 50, and 100 MUg L-1), while retarded growth and development were found at high concentrations of Pb2+ (1000 and 2000 MUg L 1). In addition, Pb2+ exposure induced morphological abnormalities, which were characterized by edema at tail, wavy fin, abdominal edema, stunted growth, hyperplasia, and axial flexures in B. gargarizans embryos. Furthermore, our results showed that exposure to 2000 MUg Pb2+ L-1 decreased the transcript levels of Dio2, TRalpha, and TRbeta, but it increased Dio3 mRNA level. In contrast, exposure to 50 MUg Pb2+ L-1 increased TRalpha mRNA level and decreased Dio3 mRNA level. These results suggested that Pb2+ might have thyroid-disrupting effects, leading to the disruption of growth and development in B. gargarizans embryos. PMID- 28988275 TI - Risk factors and preventative measures of early and persistent dysphagia after anterior cervical spine surgery: a systematic review. AB - PURPOSE: To conduct a systematic review of literature to determine risk factors and preventative measures of early and persistent dysphagia after anterior cervical spine surgery (ACSS). METHODS: On March 2017, we searched the database PubMed, Medline, EMBASE, the Cochrane library, Clinical key, Springer link and Wiley Online Library without time restriction using the term 'dysphagia', 'swallowing disorders', and 'anterior cervical spine surgery'. Selected papers were examined for the level of evidence by published guidelines as level I, level II, level III, level IV studies. We investigated risk factors and preventative measures of early or persistent dysphagia after ACSS from these papers. RESULTS: The initial search yielded 515 citations. Fifty-nine of these studies met the inclusion and exclusion criteria. Three of them were level I evidence studies, 29 were level II evidence studies, 22 were level III evidence studies, and 3 were level IV evidence studies. Preventable risk factors included prolonged operative time, use of rhBMP, endotracheal tube cuff pressure, cervical plate type and position, dC2-C7 angle, psychiatric factors, tobacco usage, prevertebral soft tissue swelling, SLN or RLN palsy or injury of branches. Preventative measures included preoperative tracheal traction exercise, maintaining endotracheal tube cuff pressure at 20 mm Hg, avoiding routine use of rhBMP-2, use of zero-profile implant, use of Zephir plate, use of new cervical retractor, steroid application, avoiding prolonged operating time, avoiding overenlargement of cervical lordosis, decreasing surgical levels, ensuring knowledge of anatomy of superior laryngeal nerve and recurrent laryngeal nerve, to comfort always, patients quitting smoking and doctors ensuring improved skills. Unpreventable risk factors included age, gender, multilevel surgery, revision surgery, duration of preexisting pain, BMI, blood loss, upper levels, preoperative comorbidities and surgical type. CONCLUSION: Adequate preoperative preparation of the patients including preoperative tracheal traction exercise and quitting smoking, proper preventative measures during surgery including maintaining endotracheal tube cuff pressure at 20 mm Hg, avoiding routine use of rhBMP-2, use of zero-profile implant, use of Zephir plate, use of new cervical retractor, steroid application, avoiding prolonged operating time, avoiding overenlargement of cervical lordosis and decreasing surgical levels, doctors ensuring knowledge of anatomy, improved surgical techniques and to comfort always are essential for preventing early and persistent dysphagia after ACSS. PMID- 28988276 TI - Vegaviidae, a new clade of southern diving birds that survived the K/T boundary. AB - The fossil record of Late Cretaceous-Paleogene modern birds in the Southern Hemisphere includes the Maastrichtian Neogaeornis wetzeli from Chile, Polarornis gregorii and Vegavis iaai from Antarctica, and Australornis lovei from the Paleogene of New Zealand. The recent finding of a new and nearly complete Vegavis skeleton constitutes the most informative source for anatomical comparisons among Australornis, Polarornis, and Vegavis. The present contribution includes, for the first time, Vegavis, Polarornis, and Australornis in a comprehensive phylogenetic analysis. This analysis resulted in the recognition of these taxa as a clade of basal Anseriformes that we call Vegaviidae. Vegaviids share a combination of characters related to diving adaptations, including compact and thickened cortex of hindlimb bones, femur with anteroposteriorly compressed and bowed shaft, deep and wide popliteal fossa delimited by a medial ridge, tibiotarsus showing notably proximally expanded cnemial crests, expanded fibular crest, anteroposterior compression of the tibial shaft, and a tarsometatarsus with a strong transverse compression of the shaft. Isolated bones coming from the Cretaceous and Paleogene of South America, Antarctica, and New Zealand are also referred to here to Vegaviidae and support the view that these basal anseriforms were abundant and diverse at high southern latitudes. Moreover, vegaviids represent the first avian lineage to have definitely crossed the K-Pg boundary, supporting the idea that some avian clades were not affected by the end Mesozoic mass extinction event, countering previous interpretations. Recognition of Vegaviidae indicates that modern birds were diversified in southern continents by the Cretaceous and reinforces the hypothesis indicating the important role of Gondwana for the evolutionary history of Anseriformes and Neornithes as a whole. PMID- 28988277 TI - A physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model of the histone deacetylase (HDAC) inhibitor vorinostat for pediatric and adult patients and its application for dose specification. AB - PURPOSE: This study aimed at recommending pediatric dosages of the histone deacetylase (HDAC) inhibitor vorinostat and potentially more effective adult dosing regimens than the approved standard dosing regimen of 400 mg/day, using a comprehensive physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) modeling approach. METHODS: A PBPK/PD model for vorinostat was developed for predictions in adults and children. It includes the maturation of relevant metabolizing enzymes. The PBPK model was expanded by (1) effect compartments to describe vorinostat concentration-time profiles in peripheral blood mononuclear cells (PBMCs), (2) an indirect response model to predict the HDAC inhibition, and (3) a thrombocyte model to predict the dose-limiting thrombocytopenia. Parameterization of drug and system-specific processes was based on published and unpublished in silico, in vivo, and in vitro data. The PBPK modeling software used was PK-Sim and MoBi. RESULTS: The PBPK/PD model suggests dosages of 80 and 230 mg/m2 for children of 0-1 and 1-17 years of age, respectively. In comparison with the approved standard treatment, in silico trials reveal 11 dosing regimens (9 oral, and 2 intravenous infusion rates) increasing the HDAC inhibition by an average of 31%, prolonging the HDAC inhibition by 181%, while only decreasing the circulating thrombocytes to a tolerable 53%. The most promising dosing regimen prolongs the HDAC inhibition by 509%. CONCLUSIONS: Thoroughly developed PBPK models enable dosage recommendations in pediatric patients and integrated PBPK/PD models, considering PD biomarkers (e.g., HDAC activity and platelet count), are well suited to guide future efficacy trials by identifying dosing regimens potentially superior to standard dosing regimens. PMID- 28988278 TI - Impaired vascular endothelial function in patients with diabetic macular edema. PMID- 28988279 TI - Caffeic acid combined with autoclaved Leishmania major boosted the protection of infected BALB/c mice by enhancing IgG2 production, IFN-gamma/TGF-beta and iNO synthase/arginase1 ratios, and the death of infected phagocytes. AB - BACKGROUND: Immunization with killed Leishmania promastigotes without adjuvant was considered as safe, but gave variable rates of protection. Taking advantage of the immuno-modulatory effect of caffeic acid (CA), a natural polyphenolic antioxidant, we investigated its potentiating effect in autoclaved Leishmania major (ALM)-induced protection of Leishmania major-infected BALB/c. METHODS: First, BALB/c mice were sensitized for 6 weeks either with CA, or ALM alone or combined with caffeic acid (ALM-CA) or Freund's adjuvant (ALM-FA), and subsequently infected with L. major promastigotes. Second, to test the curative effect, CA was given daily for 5 weeks to susceptible mice, starting on week 4 post-infection. Sera, footpads and lymph nodes (LNs) were collected at week 9 post-infection and submitted to biochemical or histological analyses. RESULTS: Compared to the respective controls, our results showed that CA directly healed footpad lesions and reduced the hallmarks of cutaneous leishmaniasis including oxidative inflammation, parasite load, and phagocytes influx and infestation. In sensitized mice, the protection enhanced gradually from ALM-FA, CA, ALM to ALM-CA in parallel to decreased seric IgGt levels. In contrast to ALM-FA, the combined effect of ALM and CA increased specific isotype IgG2, and decreased IL-17 and MCP 1, and phagocyte influx, as attested by the concomitant reduction in myeloperoxidase (MPO) and alpha-naphthyl acetate esterase (ANAE) activities. ALM CA shifted IFN-gamma/TGF-beta and iNO synthase/arginase1 (iNOS/Arg1) balances in a Th1 immune response that control efficiently cutaneous lesions and LNs hypertrophy, and reactivate the death of infected phagocytes. CONCLUSIONS: Therefore, CA combined with ALM synergizes with L. major antigens for priming innate cells, through early polarization to optimal Th1 response that leads to IFN-gamma and iNOS-dependent leishmanicidal activity of neutrophils and macrophages. PMID- 28988280 TI - Echocardiographic features in patients with ANCA-associated vasculitis within 3 months before and after diagnosis. AB - We investigated the all-inclusive echocardiographic features in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) within 3 months before and after diagnosis. We reviewed the medical records of 89 AAV patients taking echocardiography and 35 age- and gender-matched controls. We collected clinical and laboratory data and echocardiographic results. We compared the variables between patients with AAV of each variant and controls and among those with microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA) and eosinophilic GPA (EGPA). The mean age and period from diagnosis to echocardiography were 54.5 years (30 men) and 1.4 months. The mean age of controls was 51.6 years. AAV patients exhibited lower mean left ventricle ejection fraction (LVEF) (64.0 vs. 69.1%, P = 0.002) and higher mean E/E' ratio (11.7 vs. 8.8, P = 0.001) and right ventricle systolic pressure (RVSP) (30.2 vs. 23.2 mm Hg, P < 0.001) than the controls. Each variant of AAV presented a different pattern of echocardiographic features in comparison with controls. MPA patients exhibited systolic and diastolic dysfunctions and pulmonary arterial hypertension more often than controls. Meanwhile, GPA patients exhibited only diastolic dysfunction, and EGPA patients had systolic dysfunction and pulmonary arterial hypertension more frequently than controls. No meaningful differences in echocardiographic features appeared among AAV variants. AAV patients exhibited reduced systolic function and advanced diastolic dysfunctions and pulmonary arterial hypertension near the time of diagnosis compared with controls. Each variant of AAV presented a different pattern in echocardiographic features. PMID- 28988281 TI - Corynebacterium glutamicum WhcD interacts with WhiA to exert a regulatory effect on cell division genes. AB - Corynebacterium glutamicum WhcD plays an important regulatory role in cell division. Binding of WhcD to the promoter region of its target genes, such as ftsZ, was observed by electrophoretic mobility shift assays (EMSA) using purified fusion proteins; however, binding could only be observed in the presence of WhiA. Although WhcD alone did not bind to the DNA, it stimulated binding of WhiA to the promoter region of the cell division gene ftsZ. Binding of WhcD and WhiA to DNA did not occur in the presence of the oxidant diamide. Purified WhcD and WhiA physically interacted in vitro. The presence of diamide did not disrupt the WhcD WhiA interaction but affected binding of WhiA to the promoter region of ftsZ. The GACAC motif and adjacent sequences were found to be important for binding of the WhcD-WhiA complex to the DNA. Collectively, our results suggest that WhcD enhances the WhiA DNA-binding activity by physically interacting with WhiA. In addition, loss of WhiA DNA-binding activity in the presence of an oxidant agent may suggest a role for this protein as a switch that controls cell division in cells under oxidative stress. PMID- 28988283 TI - Determinants of Child Attachment in the Years Postpartum in a High-Risk Sample of Immigrant Women. AB - Our goal was to examine maternal mental health and associated stresses in a sample of high-risk immigrant mothers, and its association with child insecure attachment in the years following childbirth. Mothers and their child (Mage = 37 months) were recruited through a Health and Social Service organization in the Parc-Extension neighborhood in Montreal, Quebec. Mothers completed the Hopkins Symptoms Checklist (HSCL-25), the Multidimensional Scale of Perceived Social Support (MPSS) and a sociodemographic questionnaire that included questions on premature delivery and birth weight. Attachment behaviors were coded out of a videotaped free play sequence using the Preschool and Early School-Age Attachment Rating Scales (PARS). Analysis revealed high levels of clinical anxiety and depression, low social support and low attachment security. Significant mean differences and associations were found between anxiety, depression, social support, preterm delivery and child attachment. These results underscore the importance of screening for anxiety and depression early in the postnatal years, in order to prevent associated consequences such as child insecure attachment. Results also highlight the importance of building positive social networks, especially with immigrant populations. PMID- 28988282 TI - Biogenic and Risk Elements in Wines from the Slovak Market with the Estimation of Consumer Exposure. AB - Wine consumption delivers macroelements and microelements necessary for the proper metabolism. On the other hand, wine can be an important source of toxic metals. The aim of this study was to estimate the concentrations of Ca, Cd, Cu, Fe, Hg, Mg, Ni, Pb, and Zn in the Slovak and non-Slovak wines. The concentration of metals was evaluated with respect to the type, the alcohol content, and the age of Slovak wine. The general scheme of concentrations found was as follows Ca > Mg > Fe > Zn > Pb > Cd > Ni > Cu > Hg. The type of wine and the alcohol content do not have a significant impact on metal concentrations. Also, the age of wine has no influence on the mean concentration of metals, except for Zn. Metal concentrations in Slovak and non-Slovak wines indicate similar contents of metals, except for Ni. The contribution to both dietary reference values (DRVs) and provisional tolerable weekly intake (PTWI) evaluations in the Slovak wine suggested low dietary exposure to Ca, Cu, Fe, Mg, Ni, Zn, Cd, Hg, and Pb, respectively. However, we do not suggest that the consumption of all Slovak wines is healthy. The maximum Pb concentrations in Slovak wines exceed the maximum permitted level proposed by the European Commission. This might be proved by the results of the margin of the exposure (MOE) value evaluation in the samples containing the maximum Pb concentrations, showing a high risk of CKD and SBP in high and extreme consumption groups. PMID- 28988284 TI - Morphological and morphometrical changes on adult Wistar rat testis caused by chronic sodium arsenite exposure. AB - Arsenic is a contaminant that occurs naturally in the environment, and it is related to several diseases, such as cancer and severe metabolic diseases. Sodium arsenite effects on testes rats are not fully understood regarding morphology and stereology; thus, it becomes necessary to evaluate possible changes in these parameters under low concentrations and simulating occupational exposure. Therefore, the aim of this study was to analyze the morphometrical and stereological changes on rat testis treated with sodium arsenite. The treatment was accomplished using 5 mg/kg of sodium arsenite by gastric gavage in Wistar rats, which experiment lasted 8 weeks. Organs were weighed and gonadosomatic index (GSI) was calculated. Using the software Image Pro Plus, seminiferous tubule diameter was measured, and the volume densities of testicular parenchymal components were obtained. It was counted 200 hundred spermatozoa and classified as normal or abnormal. The parameters means of control (N = 5) and treated (N = 7) groups were compared by U Mann-Whitney's test, and the results were considered significant for P < 0.05. We observed a decrease in seminiferous tubule diameter, as well as testis weight. These finds may be related with disorders of testosterone metabolism due to activation of immunological responses of macrophage, which inhibit the steroidogenesis. Thus, we conclude that sodium arsenic does not impair the animal's general health, but its exposure induces biochemical and tissue changes. PMID- 28988286 TI - Odontology prize 2017. PMID- 28988285 TI - Human biomonitoring of eight trace elements in urine of residents living in rural areas along the Yangtze River, China. AB - The rapid economic development and industrialization have made heavy metal contamination a great public concern, especially in China. However, the levels of heavy metals in human body, especially those susceptible to the effect of industrial progression, are rarely explored. In this study, eight elements in 2643 urinary samples of individuals living in rural areas along the Yangtze River were determined through inductively coupled plasma optical emission spectrometry (As, Cr, Cu, Fe, Mn, Pb, and Zn) and TAS-990 atomic absorption spectrophotometry (Cd). Two-level regression model was applied to explore the potential factors associated with the level of the eight trace elements. After adjusting for urinary creatinine, the geometric means were 77.5, 10.98, 14.39, 13.00, 0.59, 1.51, 489.62, and 1.80 MUg/g for As, Cr, Cu, Fe, Mn, Pb, Zn, and Cd, respectively. The level of eight elements varied among individual and familial characteristics. Compared with domestic and international results, the rural residents living in riverside areas had higher level of As, Cd, Cr, Fe, and Zn. Therefore, industrial progression followed by economic development has resulted in high body burden of heavy metals. Targeted public health policies should be made to improve the local environment and the recognition of potential risk factors. PMID- 28988287 TI - Kinetic Measurements of Di- and Tripeptide and Peptidomimetic Drug Transport in Different Kidney Regions Using the Fluorescent Membrane Potential-Sensitive Dye, DiS-C3-(3). AB - Tri- and dipeptides are transported in the kidney by PEPT1 and PEPT2 isoforms. The aim of this study was to investigate differences in transport kinetics between renal brush border (BBMV) and outer medulla (OMMV) membrane vesicles (where PEPT1 and PEPT2 are sequentially available) for a range of di- and tripeptides and peptidomimetic drugs. This was accomplished through the use of the potential-sensitive fluorescent dye 3,3'-dipropylthiacarbocyanine iodide [DiS C3-(3)]. BBMV and OMMV were prepared from the rat kidney using standard techniques. The presence of PEPT1 in BBMV and PEPT2 in OMMV was confirmed using Western blotting. Fluorescence changes were measured when extravesicular medium at pH 6.6 containing 0-1 mM substrates was added to a cuvette containing vesicles pre-equilibrated at pH 7.4 and 2.71 MUM DiS-C3-(3). An increase in fluorescence intensity occurred upon substrate addition reflecting the expected positive change in membrane potential difference. Of the range of substrates studied, OMMV manifested the highest affinity to cefadroxil and valacyclovir (K m 4.3 +/- 1.2 and 11.7 +/- 3.2 uM, respectively) compared to other substrates, whilst the BBMV showed a higher affinity to Gly-His (K m 15.4 +/- 3.1 uM) compared to other substrates. In addition, OMMV showed higher affinity and capacity to Gly-Gln (K m 47.1 +/- 9.8 uM, 55.5 +/- 2.8 DeltaF/s/mg protein) than BBMV (K m 78.1 +/- 13.3 uM and 35.5 +/- 1.7 DeltaF/s/mg protein, respectively). In conclusion, this study successfully separated the expression of PEPT1 and PEPT2 into different vesicle preparations inferring their activity in different regions of the renal proximal tubule. PMID- 28988288 TI - Effects of Mechanical Complications on Radiation Exposure During Fluoroscopically Guided Gastrojejunostomy Exchange in the Pediatric Population. AB - The purpose of the article is to evaluate the effects of mechanical complications, such as clogging or coiling, of gastrojejunostomy tubes on radiation exposure during exchange in the pediatric population. In this HIPAA compliant and IRB-approved study, we retrospectively reviewed procedural records for patients undergoing gastrojejunostomy (GJ) tube exchange during a 4-month period in 2014. Success of the procedure, specifications of the tube, age, and sex of the patient as well as radiation exposure during the procedure were included. Radiation exposure was measured in fluoroscopy time and cumulative air kerma. Complications encountered during exchange were also recorded, if available. Patients presenting for gastrostomy to GJ conversions or combined procedures were excluded from the study. Ordinary and mixed effect linear regression models were used to test associations between GJ tube parameters, presence of mechanical complications, and fluoroscopy time and radiation dose. 146 patients undergoing 285 GJ exchanges met inclusion criteria over the 4-month study period (M:F 82:64). All exchanges were successful with 85 demonstrating a form of mechanical complication (44 coiled, 41 clogged). Of the reported GJ tube specifications, only tube length was significantly associated with mechanical complications (p < 0.001). The presence of mechanical complication was significantly associated with increased radiation exposure and fluoroscopy time (p < 0.0001). Mechanical complications of gastrojejunostomy tubes, such as clogging or coiling, are associated with increased radiation exposure during exchange. Strategies to decrease these complications, including re-siting the gastrostomy tract or placement of a surgical jejunostomy in the event of repeated coiling of a tube should be strongly considered. PMID- 28988289 TI - Whole body magnetic resonance imaging (WB-MRI) and brain MRI baseline surveillance in TP53 germline mutation carriers: experience from the Li-Fraumeni Syndrome Education and Early Detection (LEAD) clinic. AB - Individuals with Li-Fraumeni syndrome (LFS) have a significantly increased lifetime cancer risk affecting multiple organ sites. Therefore, novel comprehensive screening approaches are necessary to improve cancer detection and survival in this population. The objective of this study was to determine the diagnostic performance of whole body MRI (WB-MRI) and dedicated brain MRI screening as part of a comprehensive screening clinic called Li-Fraumeni Education and Early Detection (LEAD) at MD Anderson Cancer Center. Adult (>=21 year old) and pediatric (<21 year old) patients were referred to the LEAD clinic by healthcare providers or self-referred and screened at 6 month intervals. During the study period, 63 LFS individuals were seen in the LEAD clinic including 49 adults (11 male, 38 female) and 14 children (7 male, 7 female). Fifty-three of 63 potentially eligible individuals underwent baseline WB-MRI (41 adults and 12 children) with primary tumors detected in six patients, tumor recurrence in one patient and cancer metastases in one patient. Thirty-five of 63 patients (24 adults and 11 children) underwent baseline brain MRI with primary brain tumors detected in three individuals, also noted on subsequent WB-MRI scans. Three additional tumors were diagnosed that in retrospect review were missed on the initial scan (false negatives) and one tumor noted, but not followed up clinically, was prospectively found to be malignant. The high incidence of asymptomatic tumors identified in this initial screening (13%), supports the inclusion of WB-MRI and brain MRI in the clinical management of individuals with LFS. PMID- 28988290 TI - Early microbiota, antibiotics and health. AB - The colonization of the neonatal digestive tract provides a microbial stimulus required for an adequate maturation towards the physiological homeostasis of the host. This colonization, which is affected by several factors, begins with facultative anaerobes and continues with anaerobic genera. Accumulating evidence underlines the key role of the early neonatal period for this microbiota-induced maturation, being a key determinant factor for later health. Therefore, understanding the factors that determine the establishment of the microbiota in the infant is of critical importance. Exposure to antibiotics, either prenatally or postnatally, is common in early life mainly due to the use of intrapartum prophylaxis or to the administration of antibiotics in C-section deliveries. However, we are still far from understanding the impact of early antibiotics and their long-term effects. Increased risk of non-communicable diseases, such as allergies or obesity, has been observed in individuals exposed to antibiotics during early infancy. Moreover, the impact of antibiotics on the establishment of the infant gut resistome, and on the role of the microbiota as a reservoir of resistance genes, should be evaluated in the context of the problems associated with the increasing number of antibiotic resistant pathogenic strains. In this article, we review and discuss the above-mentioned issues with the aim of encouraging debate on the actions needed for understanding the impact of early life antibiotics upon human microbiota and health and for developing strategies aimed at minimizing this impact. PMID- 28988291 TI - Statistical Approaches to Address Multi-Pollutant Mixtures and Multiple Exposures: the State of the Science. AB - PURPOSE OF REVIEW: The purpose of this review is to describe the most recent statistical approaches to estimate the effect of multi-pollutant mixtures or multiple correlated exposures on human health. RECENT FINDINGS: The health effects of environmental chemicals or air pollutants have been widely described. Often, there exists a complex mixture of different substances, potentially highly correlated with each other and with other (environmental) stressors. Single exposure approaches do not allow disentangling effects of individual factors and fail to detect potential interactions between exposures. In the last years, sophisticated methods have been developed to investigate the joint or independent health effects of multi-pollutant mixtures or multiple environmental exposures. A classification of the most recent methods is proposed. A non-technical description of each method is provided, together with epidemiological applications and operational details for implementation with standard software. PMID- 28988293 TI - Persistent trigeminal artery variant terminating in the posterior inferior cerebellar artery: a case report. AB - Persistent trigeminal artery (PTA) is a rare cerebrovascular variation of remnant fetal carotid-vertebrobasilar anastomoses. The PTA variant terminates in the cerebellar artery with no direct connection to the basilar artery. We present a rare case of a PTA variant that terminated directly into the ipsilateral posterior inferior cerebellar artery. PMID- 28988292 TI - Role of cell cycle regulators in adipose tissue and whole body energy homeostasis. AB - In the course of the last decades, metabolism research has demonstrated that adipose tissue is not an inactive tissue. Rather, adipocytes are key actors of whole body energy homeostasis. Numerous novel regulators of adipose tissue differentiation and function have been identified. With the constant increase of obesity and associated disorders, the interest in adipose tissue function alterations in the XXIst century has become of paramount importance. Recent data suggest that adipocyte differentiation, adipose tissue browning and mitochondrial function, lipogenesis and lipolysis are strongly modulated by the cell division machinery. This review will focus on the function of cell cycle regulators in adipocyte differentiation, adipose tissue function and whole body energy homeostasis; with particular attention in mouse studies. PMID- 28988294 TI - Development and proposal of a scoring system for giant cell tumour of the bone around the knee. AB - PURPOSE: The purpose of this study was to provide the surgeons with effective and reliable guidelines for surgical decision-making by establishing a scoring system for giant cell tumour (GCTSS) based on evidence and expert opinion. METHODS: The modified Delphi technique and analytic hierarchy process were used to establish the GCTSS. The GCTSS was defined and classified based on different surgical methods using data from 207 patients collected retrospectively between October 2003 and December 2014. Finally, prospective data of 40 patients between December 2014 and October 2015 were used to analyze concordance between score categorization and experts' consensus on surgical procedure. RESULTS: A novel GCTSS included pathological fracture, cortical bone destruction, tumour size, and articular surface involved. The total scores ranged from 1 to 12 points. The strategy for each patient was decided: a total score of 1-4 suggested intralesional curettage alone for excellent post-operative function; 5-9 points indicated intralesional curettage with internal fixation for less surgery-related complications; and 10-12 points indicated prosthesis replacement for long-term local control. The kappa-statistic for the predictive validity of total score was 0.611. The kappa coefficient of each group represented moderate or substantial agreement, which was acceptable. The intraclass correlation coefficient for inter and intra-observer reliability of total score was 0.831 and 0.740, respectively. CONCLUSIONS: The novel GCTSS is a comprehensive scoring system with content validity that can aid surgeons in assessing the aggressiveness or severity of giant cell tumour and might become a prognostic tool for surgical decision making. PMID- 28988295 TI - Associations between clinical data and computed tomography features in patients with epidermal growth factor receptor mutations in lung adenocarcinoma. AB - BACKGROUND: To analyse the differences in computed tomography (CT) features between patients with lung adenocarcinoma who have epidermal growth factor receptor (EGFR) mutations and those who have wild-type EGFR. METHODS: Patients with lung adenocarcinoma (n = 156) were enrolled from October 2013 to March 2016, including 56 patients with wild-type EGFR and 100 patients with EGFR mutations. Two independent radiologists evaluated patient characteristics and imaging features. Chi-squared test, Fisher's exact test or ANOVA was applied to discriminate clinical and CT characteristics between the genotypes. A prediction tool for EGFR mutation was devised from principal component analysis. RESULTS: The proportion of females and non-smokers in the exon 19 deletion and exon 21 missense groups was higher than in the wild-type group (P < 0.01). Severe emphysema was higher in the wild-type group than in the exon 19 deletion group (P < 0.01). The maximum diameter in the mediastinal window (MaxDmediastinal) in the wild-type group was longer than in the exon 19 deletion and exon 21 missense groups. The minimum diameter in the mediastinal window (MinDmediastinal) in the wild-type group was also longer than in the exon 21 missense group, with a significant difference (P < 0.05). The tumor shadow disappearance rate (TDR) in the exon 19 deletion group was higher than in the wild-type group. Ground glass opacity (GGO) appeared to be more common in the exon 19 deletion group (P = 0.010). The prediction score for exon 19 deletion mutation was: 0.305 * gender + 0.254 * smoking history + 0.198 * MaxDmediastinal + TDR * 0.254 + 0.280 * GGO + 0.095 * emphysema. The sensitivity and specificity for predicting exon 19 deletion were 59.09 and 76.79%, respectively. The prediction score for the exon 21 missense mutation was: 0.354 * gender + 0.291 * smoking history + 0.410 * MaxDmediastinal + 0.408 * MinDmediastinal. The sensitivity and specificity for predicting exon 21 missense mutation were 72.34 and 78.57%, respectively. CONCLUSION: As well as gender, smoking history and GGO, adenocarcinomas with EGFR mutation were significantly associated with emphysema, TDR, and the diameter in the mediastinal window. As exon 19 deletion and 21 missense mutations might be predicted by those features, the scoring system might be valuable for clinical diagnosis. PMID- 28988296 TI - Pivotal factors for successful withdrawal of nonsteroidal anti-inflammatory drugs in rheumatoid arthritis patients in remission or with low-disease activity. AB - The purpose of this study is to examine the patient-reported outcomes (PRO) after discontinuing nonsteroidal anti-inflammatory drugs (NSAIDs) and clinical factors associated with a favorable outcome in patients with rheumatoid arthritis (RA) in remission or with low-disease activity (LDA). A 16-week prospective open-label trial was conducted at eight rheumatology clinics in Korea. RA patients with 28 joint disease activity score based on erythrocyte sedimentation rate (DAS28-ESR) < 3.2 who were on NSAIDs for more than a month were enrolled, and NSAIDs were discontinued. Acetaminophen (AAP) was used as the rescue medication, and NSAIDs were restarted when joint pain was intolerable with AAP. The endpoint was to analyze the group of patients who continued to withdraw NSAIDs. Among 109 enrolled patients, 105 completed the 16-week follow-up. Eighty-nine (84.8%) patients remained without restarting NSAIDs. In these patients, there was a slight increase in their pain levels compared with baseline (median 14.0 versus 19.0 using the pain-visual analog scale, p = 0.010). However, changes in DAS28 ESR (p = 0.638) and routine assessment of patient index data 3 (RAPID-3) (p = 0.128) were insignificant. Moreover, 66 (62.9%) patients showed sustained effectiveness on PRO without restarting NSAIDs. In the multivariate regression models, joint swelling was the detrimental factor in NSAID withdrawal (odds ratio [OR] 0.149, 95% confidence interval [CI] 0.033-0.680, p = 0.014) and sustained effectiveness (OR 0.284, 95% CI 0.091-0.883, p = 0.030). Joint pain in RA patients in remission or with LDA can be well managed without NSAIDs, especially in those without swollen joints at the time of cessation. PMID- 28988297 TI - Risk association between scleroderma disease characteristics, periodontitis, and tooth loss. AB - Systemic sclerosis (SSc) is a multi-system disorder that can have significant adverse effects on the health of the mouth. The aim of this study was to investigate the associations between the disease characteristics of SSc, periodontal disease (PD), and tooth loss. Fifty-four patients affected by SSc and 55 non-diseased controls were matched for age and gender. SSc was characterized in subtypes and with the mean duration of disease and the Modified Rodnan Skin Score [mRSS]. Patients were surveyed and examined through the evaluation of the periodontal parameters and the number of teeth. A logistic regression analysis showed that patients with SSc presented a higher number of missing teeth (p = 0.001) and a significant median increased odds 2.95 (95% CI 1.26 to 6.84) of PD (defined as clinical attachment loss, CAL) compared to nondiseased controls (6.83, 95% CI 1.94 to 24.36). Moreover, the fewer values of PD was correlated with mRSS in the total SSc group and with the mean duration of disease in patients with limited SSc (p = 0.007), even after adjusting this correlation with the presence of the major organ involvement. This study showed that patients with SSc presented increased odds of PD and tooth loss compared to non-diseased controls. In SSc patients, the magnitude of PD was strongly associated with the mRSS and with the mean duration of the disease. The clinicians should be aware of the potential systemic health problems related to PD. PMID- 28988298 TI - Is There a Return on a Children's Hospital's Investment in a Pediatric Residency's Community Health Track? A Cost Analysis. AB - Academic Medical Centers incur significant expenses associated with training residents and caring for underserved populations. No previous studies have analyzed hospital-level graduate medical education economics for pediatric residency training. Using data from the 2010-2011 academic year, we quantified total direct costs per year for training 12 community health track (CHT) residents. Utilizing sensitivity analyses, we estimated revenues generated by residents in inpatient and outpatient settings. The total yearly direct cost of training 12 CHT residents was $922,640 including salaries, benefits, and administrative costs. The estimated additional yearly inpatient net revenue from attending-resident clinical teams compared to attendingonly service was $109,452. For primary care clinics, the estimated yearly revenue differential of resident preceptor teams was $455,940, compared to attending-only clinics. The replacement cost of 12 CHT residents with advanced practitioners was $457,596 per year.This study suggests there is positive return on a children's hospital's investment in a CHT. PMID- 28988299 TI - Interrelationships among trace metals and metallothionein in digestive glands and gills for field samples of Merceneria merceneria. AB - More widespread use of metallothionein (MT) as a biomarker for trace metal pollution continues to be partly dependent on obtaining reliable baseline concentrations and identifying increased induction of the enzyme with only modest increases in metal concentrations. In this study, new data on metals and MT levels in whole clams tissue, gills, and digestive glands from field samples and in sediments are presented. Concentrations of Cd, Cu, Fe, and Zn in depurated (24 h) clam samples of digestive glands, gills, and the whole clam Merceneria merceneria from the Indian River Lagoon, Florida, varied with location and showed moderate to strong correlations among Zn, Cu, and Fe. Concentrations of metallothionein (dry wt.) ranged from 34?270 MUg/g in gills and 150-440 MUg/g in digestive glands and showed moderate to strong correlations between organs and with metal concentrations in those organs. Observed trends support increased synthesis of metallothionein with only moderate increases in metal values and in response to statistically higher sediment metal concentrations. PMID- 28988300 TI - Synthesis, Crystal Structure, Hirshfeld Surface Analysis, and Physicochemical Study of an Anhydrous Organic Acidic Cyclohexaphosphate. AB - The new organic-inorganic hybrid [5-Cl-2-(CH3)C6H3NH3]4H2P6O18 has been synthesized by the slow evaporation method. X-ray diffraction on a single crystal shows that this acidic cyclohexaphosphate crystallized in the monoclinic space group C 2/c with a = 33.89(11) A, b = 9.16(16) A, c = 13.68(3) A, beta = 91.35(2) degrees , V = 4244.9(19) A3 and Z = 4. 31P MAS-NMR and 13C CP/MAS-NMR results are in accordance with X-ray findings. Fluorescent study shows the blue photoluminescence. Furthermore, FT-IR analysis was studied and the complete vibrational assignments were done. Intermolecular interactions were analyzed using Hirshfeld surface analysis and the associated 2D fingerprint plots. PMID- 28988301 TI - Occurrence, ecological risk assessment, and spatio-temporal variation of polychlorinated biphenyls (PCBs) in water and sediments along River Ravi and its northern tributaries, Pakistan. AB - Ecological risk assessment, spatio-temporal variation, and source apportionment of polychlorinated biphenyls (PCBs) were studied in surface sediments and water from River Ravi and its three northern tributaries (Nullah Deg, Nullah Basantar, and Nullah Bein) in Pakistan. In total, 35 PCB congeners were analyzed along 27 sampling stations in pre-monsoon and post-monsoon seasons. The ?35PCB concentration ranged from 1.06 to 95.76 ng/g (dw) in sediments and 1.94 to 11.66 ng/L in water samples, with hexa-CBs and tetra-CBs as most dominant homologs in sediments and water matrixes, respectively. The ?8DL-PCB levels were 0.33-22.13 ng/g (dw) and 0.16-1.95 ng/L in sediments and water samples, respectively. The WHO-toxic equivalent values were ranged from 1.18 * 10-6 to 0.012 ng/L and 1.8 * 10-6 to 0.031 ng/g in water and sediments matrixes, respectively. The ecological risk assessment indicates considerable potential ecological risk during pre monsoon season ([Formula: see text] = 95.17) and moderate potential ecological risk during post-monsoon season ([Formula: see text] = 49.11). The industrial and urban releases were recognized as key ongoing sources for high PCB levels in environment. Therefore, we recommend more freshwater ecological studies to be conducted in the study area and firm regulatory initiatives are required to be taken in debt to the Stockholm Convention, 2001 to cop up with PCB contamination on emergency basis. PMID- 28988302 TI - Bacterial alginate production: an overview of its biosynthesis and potential industrial production. AB - Alginate is a linear polysaccharide that can be used for different applications in the food and pharmaceutical industries. These polysaccharides have a chemical structure composed of subunits of (1-4)-beta-D-mannuronic acid (M) and its C-5 epimer alpha-L-guluronic acid (G). The monomer composition and molecular weight of alginates are known to have effects on their properties. Currently, these polysaccharides are commercially extracted from seaweed but can also be produced by Azotobacter vinelandii and Pseudomonas spp. as an extracellular polymer. One strategy to produce alginates with different molecular weights and with reproducible physicochemical characteristics is through the manipulation of the culture conditions during fermentation. This mini-review provides a comparative analysis of the metabolic pathways and molecular mechanisms involved in alginate polymerization from A. vinelandii and Pseudomonas spp. Different fermentation strategies used to produce alginates at a bioreactor laboratory scale are described. PMID- 28988303 TI - High performance of alpha-defensin lateral flow assay (Synovasure) in the diagnosis of chronic knee prosthetic infections. AB - PURPOSE: This prospective study was undertaken to evaluate the diagnostic accuracy of the SynovasureTM alpha-defensin lateral flow assay to detect or exclude infection and to compare it to the sensitivity and specificity of other diagnostic criteria according to the International Consensus Group on Periprosthetic Joint Infection (PJI). METHODS: All patients who have undergone revision total knee arthroplasty (TKA) from September 2015 to July 2016 were included: 16 chronic (more than 3 months after performing arthroplasty) infections and 35 aseptic joints were identified. The diagnostic performance of single test was assessed by receiver operating characteristic (ROC) curve analyses. The sensitivity and specificity were calculated for each of the cut-off values and the area under the curve (AUC) was also calculated. RESULTS: The median synovial fluid (SF) leukocyte count, as well as the neutrophil percentage, was significantly higher in patients with PJI than in those with aseptic failure (p < 0.001). The sensitivity of alpha-defensin was 87.5% (95%; CI 74.6-94.7), the specificity was 97.1% (95% CI 86.9-99.7), the positive predictive value 93.3% (95% CI 81.8-98.1), and negative predictive value was 94.4% (95% CI 83.2-98.6). The results in terms of sensitivity and negative predictive value were greater than those of the other tests (cultures, synovial cell count, erythrocyte sedimentation rate, and C-reactive protein). The diagnostic accuracy of alpha defensin, with an area under the curve of 0.92, was found to be higher than all the minor criteria for PJI. CONCLUSIONS: In this study, the alpha-defensin lateral flow test was found to have the highest performance of all tests studied to identify PJI. SynovasureTM holds the potential to be included in the daily clinical practice. LEVEL OF EVIDENCE: Level I diagnostic study. PMID- 28988304 TI - Levels of plasma and fecal glucocorticoid metabolites following an ACTH challenge in male and female coyotes (Canis latrans). AB - Knowledge of endocrine stress responses can be advantageous for understanding how animals respond to their environment. One tool in wildlife endocrinology is to measure the adrenocortical activity as a parameter of disturbance of animals. Fecal glucocorticoid metabolites (GCMs) provide a noninvasive assessment of adrenocortical activity. Using an adrenocorticotropic hormone (ACTH) challenge administered to 28 captive coyotes (Canis latrans), we measured the levels of plasma cortisol, and fecal cortisol and corticosterone metabolites (i.e., GCMs). Our goal was to determine the dose-response in the plasma and fecal samples following the injection and determine if there were effects of sex, age, and time of day. Specifically, animals were anesthetized for ~ 90 min with treatment animals intravenously injected with exogenous ACTH and control animals receiving saline. We collected blood samples prior to injection and at 4 different time points post-injection. We also collected fecal samples 2 days pre- and 2 days post-injection to measure fecal GCMs and determine if an endocrine stress response could be detected in fecal samples. We found a definite response in cortisol levels in the plasma for coyotes to the ACTH challenge. There was a response in fecal corticosterone 1 day post-injection, but the control males showed a similar response indicating a handling effect. Fecal cortisol levels did not indicate a response to the ACTH challenge, and were significantly lower than corticosterone concentrations. We also found significant sex, but not age or diurnal, differences in fecal GCMs. Radioimmunoassays for fecal corticosterone levels appeared to be a reliable indicator of physiological stress in coyotes. PMID- 28988305 TI - Rapidly progressive Aspergillus meningitis successfully treated with voriconazole and corticosteroids. PMID- 28988307 TI - Effects of normoxic and hypoxic exercise regimens on lymphocyte apoptosis induced by oxidative stress in sedentary males. AB - PURPOSE: Oxidative stress-induced lymphocyte apoptosis is linked to hypoxemic individuals suffering from cardiopulmonary disorders or exposed to hypoxic environments. What kind of the exercise strategy under hypoxic condition improves exercise performance and simultaneously minimizes lymphocyte dysfunction caused by oxidative stress has not yet been established. This study elucidates how various exercises regimens with/without hypoxia affect lymphocyte apoptosis induced by oxidative stress. METHODS: A total of 60 sedentary males were randomly divided into five groups. Each group (n = 12) received one of the five interventions: hypoxic-absolute exercise (HAT, 50%W max under 15%O2), hypoxic relative exercise (HRT, 50% heart rate reserve under 15%O2), normoxic exercise (NT, 50%W max under 21%O2), hypoxic control (HC, resting under 15%O2), or normoxic control (NC, resting under 21%O2) for 30 min/day, 5 days/week for 4 weeks. RESULTS: Before the intervention, the graded exercise test (GXT, progressive exercise up to VO2max) decreased the surface thiol level on lymphocytes and subsequently augmented the extents of H2O2-induced mitochondria transmembrane potential (MTP) diminishing, caspase 3/8/9 activations, and phosphotidyl serine (PS) exposure in lymphocytes. However, 4 weeks of NT, HRT, or HAT reduced the extents of surface thiol decreasing on lymphocytes and H2O2 induced MTP diminishing, caspase 3/8/9 activations, and PS exposure in lymphocytes following GXT. Moreover, the HAT group exhibited greater improvements in pulmonary ventilation and VO2max than either NT or HRT group did. CONCLUSIONS: Exercise training with/without hypoxic exposure effectively alleviates lymphocyte apoptosis induced by oxidative stress following strenuous exercise. However, the HAT is superior to the NT or HRT for enhancing aerobic capacity. PMID- 28988306 TI - Nanoscale wide-band semiconductors for photocatalytic remediation of aquatic pollution. AB - Water pollution is a serious challenge to the public health. Among different forms of aquatic pollutants, chemical and biological agents create paramount threat to water quality when the safety standards are surpassed. There are many conventional remediatory strategies that are practiced such as resin-based exchanger and activated charcoal/carbon andreverse osmosis. Newer technologies using plants, microorganisms, genetic engineering, and enzyme-based approaches are also proposed for aquatic pollution management. However, the conventional technologies have shown impending inadequacies. On the other hand, new bio-based techniques have failed to exhibit reproducibility, wide specificity, and fidelity in field conditions. Hence, to solve these shortcomings, nanotechnology ushered a ray of hope by applying nanoscale zinc oxide (ZnO), titanium dioxide (TiO2), and tungsten oxide (WO3) particles for the remediation of water pollution. These nanophotocatalysts are active, cost-effective, quicker in action, and can be implemented at a larger scale. These nanoparticles are climate-independent, assist in complete mineralization of pollutants, and can act non-specifically against chemically and biologically based aquatic pollutants. Photocatalysis for environmental remediation depends on the availability of solar light. The mechanism of photocatalysis involves the formation of electron-hole pairs upon light irradiations at intensities higher than their band gap energies. In the present review, different methods of synthesis of nanoscale ZnO, TiO2, and WO3 as well as their structural characterizations have been discussed. Photodegradation of organic pollutants through mentioned nanoparticles has been reviewed with recent advancements. Enhancing the efficacy of photocatalysis through doping of TiO2 and ZnO nanoparticles with non-metals, metals, and metal ions has also been documented in this report. PMID- 28988308 TI - Improving the role of echocardiography in studying the right ventricle of repaired tetralogy of Fallot patients: comparison with cardiac magnetic resonance. AB - Right ventricular (RV) evaluation represents one of the major clinical tasks in the follow-up of repaired tetralogy of Fallot patients (rToF) with pulmonary valve regurgitation, as both severe RV dilatation and dysfunction are key factors in defining the need of pulmonary valve replacement. The aim of our study was to report the diagnostic accuracy of echocardiography in the identification of rToF patients with severely dilated and/or depressed RV as compared to cardiac magnetic resonance (CMR). Among our patients with rToF, a subgroup of 95 (17.6 +/ 6.8 years; 60% male), who underwent right ventricular qualitative and quantitative evaluation with CMR following echocardiographic suspicion of severe dilation/dysfunction, were included in the analysis. When comparing echocardiographic RV functional parameters to CMR findings, we found no association between CMR-ejection fraction (EF) and either tricuspid annulus plane systolic excursion (TAPSe) nor tissue Doppler systolic tricuspid excursion velocity (all p = ns). In contrast RVFAC was strongly associated with CMR-EF (r = 0.44; p < 0.01) as well as to longitudinal components of RV mechanics including tissue Doppler s' (r = 0.40; p < 0.01) and TAPSE (r = 0.36; p < 0.01). When comparing echocardiographic and CMR structural parameters of the RV, we found that CMR RV volume was strongly related to echocardiographic measurements of RV end diastolic area (from the 4 chamber apical view) and with proximal parasternal short axis right ventricle outflow-dimension. Accordingly a regression model was derived from multiple regression analysis, which allows a more accurate estimate of CMR RV volume from echocardiography (r2 = 0.59, p < 0.001). Our study demonstrates a significant, although imperfect, correlation between echocardiographic and CMR RV functional and geometrical parameters. Combining echocardiographic measures of RV inflow and RV outflow, we deliver a simple formula to estimate CMR-RV volume, improving the echocardiographic accuracy in RV volume quantification. PMID- 28988309 TI - Durable Benefit of Particle Occlusion of Systemic to Pulmonary Collaterals in Select Patients After Superior Cavopulmonary Connection. AB - Systemic to pulmonary arterial collaterals (SPC) are commonly found in patients undergoing staged operative palliation for single ventricle heart disease. Occlusion of SPC as part of pre-Fontan catheterization has been shown to improve hemodynamics acutely. Anecdotally, the effect of this intervention appears to be transient, and to our knowledge there is no data supporting its durability in these patients. Between 1/1/2016 and 5/1/2017, 24 children underwent Glenn operations at our institution. Of these, 3 patients had signs and symptoms deteriorating clinical status suggestive of volume overload in the period between their Glenn operation and Fontan completion, prompting heart catheterization. SPC were occluded with a combination of polyvinyl alcohol embolization particles, and in some cases coils or vascular plugs. Clinical course and data from echocardiograms and serial catheterizations are presented. SPC occlusion was performed over 6 procedures in 3 subjects with technical success in each case. Hemodynamic evaluation was repeated in 2/3 patients with improvement in collateral burden and hemodynamics in both cases. One patient previously thought to be unsuitable for Fontan completion improved sufficiently to undergo late Fontan completion, which was ultimately successful. In all patients, there was improvement in clinical status. In patients with severe SPC collateral durable benefit was seen, suggesting that in certain cases intervention on SPC remote from Fontan completion may have clinical benefit. PMID- 28988310 TI - Spatio-temporal flowering patterns in Mediterranean Poaceae. A community study in SW Spain. AB - This study focused on phenological timing and spatial patterns in 30 Poaceae species flowering in spring in different types of plant cover (scrub, riverbank and pasture). Grass community composition was studied, and the influence of species and plant cover on the start date and duration of flowering was assessed from March to June in both 2014 and 2015. Twenty-nine sampling sites were selected for phenological monitoring using the BBCH scale. Data were subjected to GLMM analyses. Binary discriminant analysis revealed differences in grass community composition as a function of plant cover type; scrub cover comprised a considerably larger number of species than those in riverbank and pasture. Moreover, more species diversity was observed in 2014 than in 2015 with a drier and stressed pre-flowering period. Differences on phenology were also recorded between plant cover types and study years. Species in pasture and riverbank flowered before (113.4 days; 116.1 days) than species in scrub (120.9 days), being these species with shorter flowering length because they are more exposed to the characteristic of the Mediterranean region during the summer. In general, flowering onset occurred later in 2014 (118.2 days) than in 2015 (115.8 days), probably attributable to precipitation occurring during March. On the other hand, spatial autocorrelation within some cover types has been observed, showing spatial patterns exist at a smaller scale. The findings of this study contribute to a better understanding of grass phenology in different environments. PMID- 28988311 TI - Addition of large amount of municipal sewage sludge as raw material in cement clinker production. AB - Two addition modes were used to explore the maximum addition of municipal sewage sludge as a raw material in cement clinker production. The clinker and cement product quality were determined by chemical analysis, cement quality testing, characterization of the clinker crystalline phases, and leaching tests. Municipal sewage sludge addition in the raw mix could be up to 30% based on the cement clinker moduli, and the cement quality met the P.O 42.5 cement standard (GB 175 2007). The amount of municipal sewage sludge added based on the direct addition mode should be less than 15% because of an insufficient early-term cement strength (third day). The leaching concentrations of heavy metals in all cements were below the threshold (GB 30760-2014) using the latest leaching procedure (GB 30810-2014). The municipal sewage sludge could be used with a high addition (30%) in the raw mix as a raw material in cement clinker production. PMID- 28988312 TI - Contamination occurs during ACL graft harvesting and manipulation, but it can be easily eradicated. AB - PURPOSE: Why anterior cruciate ligament (ACL) autograft soaking in a 5 mg/ml vancomycin solution decreases the rate of infection has not been well-explained. One hypothesis is that grafts can be contaminated during harvesting and vancomycin eradicates the bacteria. The purpose of the present study is to assess how the vancomycin solution acts against ACL graft contamination during graft harvesting and preparation. METHODS: The study was carried out in three university hospitals over a period of 6 months. After sample size calculation, 50 patients were included in the study. Three samples were taken from each ACL graft. Sample 1 was obtained immediately after graft harvesting. After graft manipulation and preparation, the remaining tissue was divided into two parts. The raw sample was denominated sample 2 and sample 3 consisted of the rest of the remaining tissue that had been soaked in the vancomycin solution. All the cultures were incubated at 37 degrees C with 5% CO2 in agar plates for 7 days (aerobically) or 14 days (anaerobically) and inspected daily for microbial growth. Any bacterial growth and the number of colony forming units were reported. RESULTS: In seven cases (14%), either sample 1 or sample 2 was positive. In five of the cases (10%), only the sample after graft preparation was positive (sample 2). In two cases (4%), sample 1 and sample 2 were positive for the same bacteria. Isolated microorganisms corresponded to coagulase-negative staphylococci (CNS) and Propionibacterium acnes. No bacterial growth was observed in sample 3 (p < 0.001). Thus, none of those seven positive cases (0%) were positive after vancomycin soaking (p < 0.001). CONCLUSION: In the series, ACL graft harvesting and manipulation leads to bacterial contamination in 14% of the cases. This contamination is fully eradicated after soaking in the vancomycin solution in this series. LEVEL OF EVIDENCE: Level II. PMID- 28988313 TI - Thermal windows and metabolic performance curves in a developing Antarctic fish. AB - For ectotherms, temperature modifies the rate of physiological function across a temperature tolerance window depending on thermal history, ontogeny, and evolutionary history. Some adult Antarctic fishes, with comparatively narrow thermal windows, exhibit thermal plasticity in standard metabolic rate; however, little is known about the shape or breadth of thermal performance curves of earlier life stages of Antarctic fishes. We tested the effects of acute warming ( 1 to 8 degrees C) and temperature acclimation (2 weeks at - 1, 2, 4 degrees C) on survival and standard metabolic rate in early embryos of the dragonfish Gymnodraco acuticeps from McMurdo Sound, Ross Island, Antarctica. Contrary to predictions, embryos acclimated to warmer temperatures did not experience greater mortality and nearly all embryos survived acute warming to 8 degrees C. Metabolic performance curve height and shape were both significantly altered after 2 weeks of development at - 1 degrees C, with further increase in curve height, but not alteration of shape, with warm temperature acclimation. Overall metabolic rate temperature sensitivity (Q 10) from - 1 to 8 degrees C varied from 2.6 to 3.6, with the greatest thermal sensitivity exhibited by embryos at earlier developmental stages. Interclutch variation in metabolic rates, mass, and development of simultaneously collected embryos was also documented. Taken together, metabolic performance curves provide insight into the costs of early development under warming temperatures, with the potential for thermal sensitivity to be modified by dragonfish phenology and magnitude of seasonal changes in temperature. PMID- 28988314 TI - The prostate response to prolactin modulation in adult castrated rats subjected to testosterone replacement. AB - Despite the androgenic dependence, other hormones, growth factors, and cytokines are necessary to support prostatic growth and maintain the glandular structure; among them, prolactin is a non-steroidal hormone secreted mainly by the pituitary gland. However, extra-pituitary expression of prolactin, such as in the prostate, has also been demonstrated, highlighting the paracrine and autocrine actions of prolactin within the prostate. Here, we investigated whether prolactin modulation alters ventral prostate (VP) morphophysiology in adult castrated rats. Sprague Dawley rats were castrated and after 21 days, divided into ten experimental groups (n = 6/group): castrated control: castrated animals that did not receive treatment; castrated+testosterone: castrated animals that received T (4 mg/kg/day); castrated+PRL (PRL): castrated animals receiving prolactin (0.3 mg/kg/day); castrated+T+PRL: castrated animals that received a combination of testosterone and prolactin; and castrated+bromocriptine (BR): castrated animals that received bromocriptine (0.4 mg/kg/day). The control group included intact animals. The animals were treated for 3 or 10 consecutive days. At the end of experimental period, the animals were euthanized, and the blood and VP lobes were collected and analyzed by different methods. The main findings were that the administration of prolactin to castrated rats did not exert anabolic effects on the VP. Although we observed activation of downstream prolactin signaling after prolactin administration, this was not enough to overcome the prostatic androgen deficiency. Likewise, there was no additional glandular involution in the castrated group treated with bromocriptine. We concluded that despite stimulating the downstream signaling pathway, exogenous prolactin does not act on VP in the absence or presence of high levels of testosterone. PMID- 28988315 TI - Serum gamma-glutamyltransferase is inversely associated with dietary total and coffee-derived polyphenol intakes in apparently healthy Japanese men. AB - PURPOSE: Serum gamma-glutamyltransferase (GGT) has been proposed as a marker of oxidative stress. Here, we examined the association between serum GGT and the dietary intake of polyphenols, which have antioxidant properties. METHODS: A cross-sectional survey including 7960 apparently healthy Japanese men (aged 22-86 years) who participated in health checkups was conducted in Shizuoka, Japan. We analyzed these subjects' clinical serum parameters and lifestyle factors, including dietary polyphenol intake, which was evaluated by a self-administered questionnaire and by matching the subjects' food consumption data with our original polyphenol content database. RESULTS: The average intake of polyphenols was 1157 +/- 471 mg/day, and green tea was the largest source of polyphenols at 40%, followed by coffee at 36%. Dividing the population according to quintiles of total polyphenol intake, the difference in polyphenol intake from coffee between the groups was much greater than the difference in polyphenol intake from green tea. The analysis of the association between polyphenol intake and biological parameters showed a significant negative association between polyphenol intake and the levels of systolic and diastolic blood pressure (SBP and DBP), GGT, and alanine aminotransferase (ALT) after adjusting for age, smoking habit, energy intake and alcohol intake. The GGT levels were inversely associated with the polyphenol intake from coffee, but not with that from green tea. Multivariable linear regression analyses demonstrated that the subjects' GGT levels were negatively and independently associated with their polyphenol intake. CONCLUSIONS: The intake of total polyphenol including coffee as a major contributor is inversely associated with the serum GGT concentration in Japanese males. PMID- 28988316 TI - Interspecies transmission of emotional information via chemosignals: from humans to dogs (Canis lupus familiaris). AB - We report a study examining interspecies emotion transfer via body odors (chemosignals). Do human body odors (chemosignals) produced under emotional conditions of happiness and fear provide information that is detectable by pet dogs (Labrador and Golden retrievers)? The odor samples were collected from the axilla of male donors not involved in the main experiment. The experimental setup involved the co-presence of the dog's owner, a stranger and the odor dispenser in a space where the dogs could move freely. There were three odor conditions [fear, happiness, and control (no sweat)] to which the dogs were assigned randomly. The dependent variables were the relevant behaviors of the dogs (e.g., approaching, interacting and gazing) directed to the three targets (owner, stranger, sweat dispenser) aside from the dogs' stress and heart rate indicators. The results indicated with high accuracy that the dogs manifested the predicted behaviors in the three conditions. There were fewer and shorter owner directed behaviors and more stranger directed behaviors when they were in the "happy odor condition" compared to the fear odor and control conditions. In the fear odor condition, they displayed more stressful behaviors. The heart rate data in the control and happy conditions were significantly lower than in the fear condition. Our findings suggest that interspecies emotional communication is facilitated by chemosignals. PMID- 28988319 TI - The selective serotonin reuptake inhibitor fluoxetine increases spontaneous afferent firing, but not mechanonociceptive sensitization, in octopus. AB - Serotonin is a widely studied modulator of neural plasticity. Here we investigate the effect of fluoxetine, a selective serotonin reuptake inhibitor, on short term, peripheral nociceptive plasticity in the neurologically complex invertebrate, octopus. After crush injury to isolated mantle (body wall) tissue, application of 10 nM fluoxetine increased spontaneous firing in crushed preparations, but had a minimal effect on mechanosensory sensitization. Effects largely did not persist after washout. We suggest that transiently elevated, endogenous serotonin may help promote initiation of longer-term plasticity of nociceptive afferents and drive immediate and spontaneous behaviors aimed at protecting wounds and escaping dangerous situations. PMID- 28988317 TI - Identification of critical amino acids in the proximal C-terminal of TREK-2 K+ channel for activation by acidic pHi and ATP-dependent inhibition. AB - TWIK-related two-pore domain K+ channels (TREKs) are regulated by intracellular pH (pHi) and Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2). Previously, Glu306 in proximal C-terminal (pCt) of mouse TREK-1 was identified as the pHi sensing residue. The direction of PI(4,5)P2 sensitivity is controversial, and we have recently shown that TREKs are inhibited by intracellular ATP via endogenous PI(4,5)P2 formation. Here we investigate the anionic and cationic residues of pCt for the pHi and ATP-sensitivity in human TREK-2 (hTREK-2). In inside-out patch clamp recordings (ITREK-2,i-o), acidic pHi-induced activation was absent in E332A and was partly attenuated in E335A. Neutralization of cationic Lys (K330A) also eliminated the acidic pHi sensitivity of ITREK-2,i-o. Unlike the inhibition of wild-type (WT) ITREK-2,i-o by intracellular ATP, neither E332A nor K330A was sensitive to ATP. Nevertheless, exogenous PI(4,5)P2 (10 MUM) abolished ITREK-2 i o in all the above mutants as well as in WT, indicating unspecific inhibition by exogenous PI(4,5)P2. In whole-cell recordings of TREK-2 (ITREK-2,w-c), K330A and E332A showed higher or fully active basal activity, showing attenuated or insignificant activation by 2-APB, arachidonic acid, or acidic pHe 6.9. ITREK-1,w c of WT is largely suppressed by pHe 6.9, and the inhibition is slightly attenuated in K312A and E315A. The results show concerted roles of the oppositely charged Lys and Glu in pCt for the ATP-dependent low basal activity and pHi sensitivity. PMID- 28988320 TI - Nanoscale zero-valent iron functionalized Posidonia oceanica marine biomass for heavy metal removal from water. AB - Because of the excellent reducing capacity of nanoscale zero-valent iron (NZVI), it can be used as alternative materials for the removal of a variety of reducible water contaminants including toxic metals. The current paper reports the research results obtained for self-prepared biosorbent, Posidonia oceanica biomass, activated in alkaline medium and functionalized with NZVI particles. The structural characteristics, surface morphology, and binding properties of the resulting nanobiosorbent are presented. Batch comparative adsorption trials including adsorption kinetics and isothermals onto raw Posidonia, Posidonia-OH and Posidonia-OH-NZVI were investigated on three heavy metal ions: Cd(II), Pb(II), and Cu(II). The nanobiosorbent showed better properties, such as high reactivity and high uptake rate through the sorption process. The toxic metal removal has been monitored in terms of pseudo-first- and pseudo-second-order kinetics, and both Langmuir- and Freundlich-type isotherm models have been used to describe the sorption mechanism. The experimental data of all studied systems showed that the uptake kinetics follow the pseudo-second-order kinetic model and the equilibrium uptake can adopt the Langmuir-type isotherm model which assumes a monolayer coverage as the adsorption saturates and no further adsorption occurs. The thermodynamic results confirm that all sorption processes were feasible, spontaneous and thermodynamically favorable. Zeta potential data displayed that Cd(II), Pb(II), and Cu(II) tend to be reduced after exposure on the Posidonia-OH NZVI surface. Furthermore, sorption competitions of the metals from binary and ternary systems were carried out onto Posidonia-OH-NZVI in order to gain further insight into the sorption efficiency of this material. Therefore, as a result, the proposed new nanobiosorbent could offer potential benefits in remediation of heavy metal-contaminated water as a green and environmentally friendly bionanocomposite. PMID- 28988321 TI - Apoptotic biomarkers in cumulus cells in relation to embryo quality in polycystic ovary syndrome. AB - PURPOSE: To investigate associations between gene expression pattern of apoptotic biomarkers in cumulus cells of polycystic ovary syndrome (PCOS) patients and the quality of oocytes and embryos. METHODS: 40 intracytoplasmic sperm injection patients, of whom 20 were PCOS and 20 were healthy women, were included in this study. Serum hormone levels were measured using Radioimmunoassay for each patient. The expression of survivin, caspase-3, and caspase-7 in 200 cumulus complexes surrounding mature oocytes (100 in PCOS versus 100 in control groups) collected individually at pick up was examined by real-time polymerase chain reaction (real-time PCR). RESULTS: The expression levels of survivin were significantly lower in PCOS patients than those of normal women while caspase-3 and caspase-7 expression levels were higher in PCOS patients (p < 0.05). There was a statistically significant correlation between the levels of these genes and embryo quality. CONCLUSIONS: This study reveals that the measurement of survivin, caspase-3, caspase-7 levels in cumulus cells of PCOS patients could be used as genetic biomarkers for oocyte and embryo selection under an ART program. However, further prospective studies are required to elucidate this issue. PMID- 28988322 TI - Multimodal Residential Treatment for Adolescent Anxiety: Outcome and Associations with Pre-treatment Variables. AB - This study aimed to determine the effect of a multimodal residential treatment program for severe adolescent anxiety, and examine whether treatment outcome was associated with pre-treatment anxiety, comorbid disorders, or participant age or gender. Participants were 70 adolescents (61.4% female, mean age = 15.4 years) with a primary anxiety disorder who received residential treatment involving cognitive behavioral therapy and medication management. Treatment outcome was assessed both as the change in adolescent-reported anxiety symptoms, and using treatment response criteria. Results indicated a strong effect of the intervention on symptoms of anxiety, depression, and anxiety-related life interference. Most pre-treatment variables were not associated with treatment outcome. However, higher adolescent-reported pre-treatment anxiety was associated with a greater reduction in anxiety at post-treatment, and the presence of a comorbid anxiety disorder was associated with poorer odds of treatment response. Findings indicate that residential treatment is a robust intervention for adolescent anxiety. PMID- 28988323 TI - Analysis of NOD-like receptor NLRP1 in multiple sclerosis families. AB - The implementation of exome sequencing technologies has started to unravel the genetic etiology of familial multiple sclerosis (MS). A homozygote p.G587S mutation in NLRP1 has been suggested as potentially causative for the onset of MS in an affected sibling pair, who later developed malignant melanoma. To validate the proposed role of recessive NLRP1 mutations in the pathological mechanisms of MS, we examined exome sequencing data from 326 MS patients from Canada for the identification of NLRP1 missense and nonsense variants. This analysis did not identify the previously described p.G587S mutation; however, three patients with potential NLRP1 compound heterozygote mutations were observed. Haplotype and segregation analyses indicate that the variants observed in these patients were inherited in cis, and do not segregate with disease within families. Thus, the analysis of MS patients from Canada failed to identify potentially pathogenic mutations in NLRP1, including the previously described p.G587S mutation. Further studies are necessary to confirm a role of NLRP1 in the pathophysiology of MS. PMID- 28988326 TI - Soil aggregate and organic carbon distribution at dry land soil and paddy soil: the role of different straws returning. AB - Agriculture wastes returning to soil is one of common ways to reuse crop straws in China. The returned straws are expected to improve the fertility and structural stability of soil during the degradation of straw it selves. The in situ effect of different straw (wheat, rice, maize, rape, and broad bean) applications for soil aggregate stability and soil organic carbon (SOC) distribution were studied at both dry land soil and paddy soil in this study. Wet sieving procedures were used to separate soil aggregate sizes. Aggregate stability indicators including mean weight diameter, geometric mean diameter, mean weight of specific surface area, and the fractal dimension were used to evaluate soil aggregate stability after the incubation of straws returning. Meanwhile, the variation and distribution of SOC in different-sized aggregates were further studied. Results showed that the application of straws, especially rape straw at dry land soil and rice straw at paddy soil, increased the fractions of macro-aggregate (> 0.25 mm) and micro-aggregate (0.25-0.053 mm). Suggesting the nutrients released from straw degradation promotes the growing of soil aggregates directly and indirectly. The application of different straws increased the SOC content at both soils and the SOC mainly distributed at < 0.53 mm aggregates. However, the contribution of SOC in macro- and micro-aggregates increased. Straw-applied paddy soil have a higher total SOC content but lower SOC contents at > 0.25 and 0.25-0.053 mm aggregates with dry land soil. Rape straw in dry land and rice straw in paddy field could stabilize soil aggregates and increasing SOC contents best. PMID- 28988325 TI - Advances in understanding the molecular mechanisms of cytoplasmic male sterility and restoration in rice. AB - Cytoplasmic male sterility (CMS) in plants is a male reproductive defect determined by mitochondrial genes and inherited maternally. CMS can be suppressed by nuclear restorer of fertility (Rf) genes. Therefore, CMS/Rf systems provide a classic model for the study of mitochondrial-nuclear interactions in plants. Moreover, CMS/Rf systems are economical, effective tools for the production of hybrid seeds. For example, CMS/Rf systems have been applied in over forty countries to breed hybrid rice (Oryza sativa L.) with improved yields due to hybrid vigor. The production of hybrid rice mainly depends on three types of CMS systems, namely Wild-Abortive type CMS (CMS-WA), Hong-Lian type CMS (CMS-HL) and Boro II type CMS (CMS-BT). Understanding the molecular mechanisms underlying these CMS/Rf systems will help us to understand mitochondrial-nuclear interactions, and accelerate the utilization of heterosis for improvement in yield. In the past decades, research benefitting from the availability of the high-quality, annotated mitochondrial and nuclear genome sequences of rice has isolated many CMS genes, identified the cognate nuclear Rf genes and studied the molecular mechanisms underlying CMS and restoration in rice. Here, we focus on recent advances in studies of the three major CMS/Rf systems in rice and discuss the key issues facing basic research and application of CMS/Rf systems in the future. PMID- 28988324 TI - Potential Sex Differences Relative to Autism Spectrum Disorder and Metals. AB - PURPOSE OF REVIEW: This study aims to summarize the current body of literature on the relationship between various toxic metals exposures (i.e., aluminum, antimony, arsenic, beryllium, cadmium, chromium, lead, manganese, and nickel) and autism spectrum disorder (ASD), with a focus on potential sex differences in these associations. RECENT FINDINGS: Sex differences in ASD diagnosis and mutagenic effects of toxic exposures indicate that sex differences may play a major part in the causal relationship of any potential associations seen; however, we were only able to find three studies that reported on sex differences in observed associations with toxic metals exposure and ASD. We also found several studies investigating associations between ASD and metals exposures, including 11 on aluminum, 6 on antimony, 15 on arsenic, 5 on beryllium, 17 on cadmium, 11 on chromium, 25 on lead, 14 on manganese, and 13 on nickel with markers of exposure in hair, urine, blood, teeth, fingernails, and air pollution. Results for each metal were conflicting, but studies on cadmium and lead yielded the highest proportion of studies with positive results (72% and 36%, respectively). Based on our examination of existing literature, the current evidence warrants a considerable need for evaluations of sex differences in future studies assessing the association between metals exposures and ASD. Additionally, failure to account for potential sex differences could result in bias and misinterpretation of exposure-disease relationships. PMID- 28988328 TI - Acacetin attenuates mice endotoxin-induced acute lung injury via augmentation of heme oxygenase-1 activity. AB - Acacetin, a natural product, has a wide spectrum of biological activities such as antioxidant properties. In the present study, we examined whether Acacetin has any beneficial role on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and, if so, whether its effect is mediated via heme oxygenase-1 (HO-1), an antioxidant enzyme playing an important role in ALI. Male BALB/c mice were stimulated with LPS intratracheal instillation to induce ALI. Acacetin was administrated 2 h after LPS challenge. Samples were harvested 10 h after LPS administration. We demonstrated that LPS challenge significantly induced lung histological alterations such as inflammation and edema. Acacetin administration notably attenuated these changes and reduced tumor necrosis factor-alpha and interleukin-1beta in lung tissues. The LPS-induced reactive oxygen species generation was markedly suppressed by Acacetin. Furthermore, Acacetin treatment significantly elevated pulmonary HO-1 and nuclear factor erythroid-2-related factor 2 (Nrf2) activities. However, the beneficial action of Acacetin was markedly abolished when pretreated with zinc protoporphyrin, an inhibitor of HO 1. In in vitro studies, Acacetin notably increased the HO-1 expression in pulmonary microvascular endothelial cells. During knockdown of Nrf2 by siRNA, the effect of Acacetin on HO-1 expression was significantly reversed. Acacetin attenuates LPS-induced ALI in mice. This protective effect of Acacetin may be mediated, in part, through an HO-1-dependent pathway. PMID- 28988329 TI - Ultrasonography and return to play of the different clinical grading of quadriceps contusions: a case series. AB - Prognostication of quadriceps contusion is based on the patient's active knee flexion after the injury. Unlike ultrasonography, clinical grading does not define the extent of soft tissue injury and may provide inaccurate time for return to play. The purposes of this report are to describe the ultrasound findings of the different clinical grading of quadriceps contusion and document the return to play of each case. Seven patients were evaluated in this series. Results showed discrepancies in the disability time between clinical grading and ultrasound findings. Clinical grading did not consistently estimate the return to play as described in previously published literature. Contusions with hyperechoic lesions had earlier return to play compared to patients with hypoechoic findings. Contusions with hypoechoic lesions might require aggressive monitoring and therapy to decrease disability time and avoid complications such as myositis ossificans. PMID- 28988330 TI - Factors influencing streambed hydraulic conductivity and their implications on stream-aquifer interaction: a conceptual review. AB - The estimation and modeling of streambed hydraulic conductivity (K) is an emerging interest due to its connection to water quality, aquatic habitat, and groundwater recharge. Existing research has found ways to sample and measure K at specific sites and with laboratory tests. The challenge undertaken was to review progress, relevance, complexity in understanding and modeling via statistical and geostatistical approaches, literature gaps, and suggestions toward future needs. This article provides an overview of factors and processes influencing streambed hydraulic conductivity (K) and its role in the stream-aquifer interaction. During our synthesis, we discuss the influence of geological, hydrological, biological, and anthropogenic factors that lead to variability of streambed substrates. Literature examples document findings to specific sites that help to portray the role of streambed K and other interrelated factors in the modeling of hyporheic and groundwater flow systems. However, studies utilizing an integrated, comprehensive database are limited, restricting the ability of broader application and understanding. Examples of in situ and laboratory methods of estimating hydraulic conductivity suggest challenges in acquiring representative samples and comparing results, considering the anisotropy and heterogeneity of fluvial bed materials and geohydrological conditions. Arriving at realistic statistical and spatial inference based on field and lab data collected is challenging, considering the possible sediment sources, processes, and complexity. Recognizing that the K for a given particle size group includes several to many orders of magnitude, modeling of streambed K and groundwater interaction remain conceptual and experimental. Advanced geostatistical techniques offer a wide range of univariate or multi-variate interpolation procedures such as kriging and variogram analysis that can be applied to these complex systems. Research available from various studies has been instrumental in developing sampling options, recognizing the significance of fluvial dynamics, the potential for filtration, transfer, and storage of high-quality groundwater, and importance to aquatic habitat and refuge during extreme conditions. Efforts in the characterization of natural and anthropogenic conditions, substrate materials, sediment loading, colmation, and other details highlight the great complexity and perhaps need for a database to compile relevant data. The effects on streambed hydraulic conductivity due to anthropogenic disturbances (in-stream gravel mining, contaminant release, benthic activity, etc.) are the areas that still need focus. An interdisciplinary (hydro-geo-biological) approach may be necessary to characterize the magnitude and variability of streambed K and fluxes at local, regional scales. PMID- 28988331 TI - Economic Burden of Herpes Zoster and Post-Herpetic Neuralgia in Adults 60 Years of Age or Older: Results from a Prospective, Physician Practice-Based Cohort Study in Kushiro, Japan. AB - BACKGROUND AND OBJECTIVE: Herpes zoster has a high incidence rate among people aged >= 60 years and can lead to serious complications such as post-herpetic neuralgia. There are currently no data on the economic burden of herpes zoster and post-herpetic neuralgia in Japan, and the objective of this study was to address this gap. METHODS: A total of 412 patients aged >= 60 years diagnosed with herpes zoster were recruited. Demographic, clinical, and healthcare resource utilization data on patients with herpes zoster or post-herpetic neuralgia collected via case report forms were used to estimate direct medical cost. Data obtained from a questionnaire survey among patients with herpes zoster/post herpetic neuralgia were used to estimate transportation cost and productivity loss. RESULTS: The mean number of outpatient visits was 5.7. Prescription medications were the main cost driver accounting for 60% of the direct medical cost. The mean direct medical and total herpes zoster-related costs per patient were Y43,925 and Y57,112, respectively, and were higher in patients with post herpetic neuralgia than in those with herpes zoster without complications. Direct medical cost represented 77%, productivity loss 19%, and transportation cost 4% of the total. CONCLUSIONS: This is the first study of the economic burden of herpes zoster and post-herpetic neuralgia in Japan and it demonstrated substantial direct medical cost as a result of the multiple outpatient visits and prescription medications required. These findings provide baseline data for possible future economic evaluations of new herpes zoster/post-herpetic neuralgia interventions. TRIAL REGISTRATION: This cost analysis is part of a prospective, physician practice-based cohort study conducted between June 2013 and February 2015 in Kushiro, Japan (Clinicaltrials.gov identifier NCT01873365, registered on 6 June, 2013). PMID- 28988332 TI - Nomogram predicting long-term survival after the diagnosis of intrahepatic recurrence of hepatocellular carcinoma following an initial liver resection : Reply to Drs. Ayubi and Safiri. PMID- 28988333 TI - Primary screw perforation or subsequent screw cut-out following proximal humerus fracture fixation using locking plates: a review of causative factors and proposed solutions. AB - The surgical treatment of proximal humerus fractures remains controversial primarily due to the high complication rate associated with the available fixation methods. In an attempt to reduce the incidence of serious complications and subsequent poor clinical outcomes, proximal humerus locking plates have become popular but even these implants cannot overcome the risk of complications, especially those associated with loss of fracture reduction and screw cut out/migration through the humeral head. In an attempt to address these issues, we have reviewed the literature, investigating the most likely causes for these predominantly mechanical complications and propose technical solutions. PMID- 28988335 TI - Sorption and desorption of organophosphate esters with different hydrophobicity by soils. AB - Organophosphate esters (OPEs) are ubiquitous contaminants with potentially hazardous effects on both the environment and human health. Knowledge about the soil sorption-desorption process of organic chemicals is important in order to understand their fate, mobility, and bioavailability, enabling an estimation to be made of possible risks to the environment and biota. The aim of this study was to use the batch equilibrium technique to evaluate the sorption-desorption behavior of seven OPEs (TCEP, TCPP, TBEP, TDCP, TBP, TPhP, and EHDP) in soils with distinctive characteristics (two unamended soils and a soil amended with sewage sludge). The equilibrium concentrations of the OPEs were determined by high performance liquid chromatography coupled to a triple quadrupole mass spectrometer (HPLC-MS/MS). All the compounds were sorbed by the soils, and soil organic carbon (OC) played an important role in this process. The sorption of the most soluble OPEs (TCEP, TCPP, and TBEP) depended on soil OC content, although desorption was >= 58.1%. The less water-soluble OPEs (TDCP, TBP, TPhP, and EHDP) recorded total sorption (100% for TPhP and EHDP) or very high sorption (>= 34.9%) by all the soils and were not desorbed, which could be explained by their highly hydrophobic nature, as indicated by the logarithmic octanol/water partition coefficient (Kow) values higher than 3.8, resulting in a high affinity for soil OC. The results of the sorption-desorption of the OPEs by soils with different characteristics highlighted the influence of these compounds' physicochemical properties and the content and nature of soil OC in this process. PMID- 28988334 TI - A systematic review of cerebral microdialysis and outcomes in TBI: relationships to patient functional outcome, neurophysiologic measures, and tissue outcome. AB - OBJECTIVE: To perform a systematic review on commonly measured cerebral microdialysis (CMD) analytes and their association to: (A) patient functional outcome, (B) neurophysiologic measures, and (C) tissue outcome; after moderate/severe TBI. The aim was to provide a foundation for next-generation CMD studies and build on existing pragmatic expert guidelines for CMD. METHODS: We searched MEDLINE, BIOSIS, EMBASE, Global Health, Scopus, Cochrane Library (inception to October 2016). Strength of evidence was adjudicated using GRADE. RESULTS: (A) Functional Outcome: 55 articles were included, assessing outcome as mortality or Glasgow Outcome Scale (GOS) at 3-6 months post-injury. Overall, there is GRADE C evidence to support an association between CMD glucose, glutamate, glycerol, lactate, and LPR to patient outcome at 3-6 months. (B) Neurophysiologic Measures: 59 articles were included. Overall, there currently exists GRADE C level of evidence supporting an association between elevated CMD measured mean LPR, glutamate and glycerol with elevated ICP and/or decreased CPP. In addition, there currently exists GRADE C evidence to support an association between elevated mean lactate:pyruvate ratio (LPR) and low PbtO2. Remaining CMD measures and physiologic outcomes displayed GRADE D or no evidence to support a relationship. (C) Tissue Outcome: four studies were included. Given the conflicting literature, the only conclusion that can be drawn is acute/subacute phase elevation of CMD measured LPR is associated with frontal lobe atrophy at 6 months. CONCLUSIONS: This systematic review replicates previously documented relationships between CMD and various outcome, which have driven clinical application of the technique. Evidence assessments do not address the application of CMD for exploring pathophysiology or titrating therapy in individual patients, and do not account for the modulatory effect of therapy on outcome, triggered at different CMD thresholds in individual centers. Our findings support clinical application of CMD and refinement of existing guidelines. PMID- 28988337 TI - EAP 2017 Congress and MasterCourse : October 12-15, 2017 Ljubljana, Slovenia. PMID- 28988336 TI - Production of the copolymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate) with varied composition using different nitrogen sources with Haloferax mediterranei. AB - The extreme haloarchaea Haloferax mediterranei accumulates poly(3-hydroxybutyrate co-3-hydroxyvalerate) (PHBV) without the need for specific precursors. In this study, growth kinetics and PHBV synthesis were characterised under nitrogen excess and nitrogen-limiting conditions in ammonium and, for the first time, nitrate. With excess nitrogen, ammonium and nitrate cultures generated 10.7 g/L biomass containing 4.6 wt% PHBV and 5.6 g/L biomass with 9.3 wt% PHBV, respectively. Copolymer composition varied with the nitrogen source used: PHBV from ammonium cultures had 16.9 mol% 3-hydroxyvalerate (HV), while PHBV from nitrate cultures contained 12.5 mol% HV. Nitrogen limitation was achieved with carbon-to-nitrogen (C/N) molar ratios of 25 or higher. Nitrogen limitation reduced biomass generation and polymer concentration, but polymer accumulation increased to 6.6 and 9.4% for ammonium and nitrate, respectively, with C/N 42. PHBV composition was also affected and cultures with lower C/N ratios produced richer HV polymers. Copolymer formation was not a uniform process: HV was only detected after a minimum accumulation of 0.45 g/L PHB and lasted for a maximum of 48 h. The understanding of copolymer synthesis and the influence of culture conditions such as the nitrogen source will help in designing novel strategies for the production of PHBV with more regular structure and material properties. PMID- 28988338 TI - Opposing collicular influences on the parafascicular (Pf) and posteromedial (POm) thalamic nuclei: relationship to POm-induced inhibition in the substantia nigra pars reticulata (SNR). AB - The superior colliculus activates the zona incerta (ZI), which sends GABAergic projections to the posteromedial (POm) thalamic nucleus. Consistent with this circuit, we previously showed that stimulation of the superior colliculus activates ZI and causes inhibition of neuronal activity in POm (Watson et al., J Neurosci 35:9463-9476, 2015). Other studies, however, have shown that collicular stimulation activates the intralaminar nuclei of the thalamus. The present study extends these reports by showing that unilateral collicular stimulation causes bilateral activation of Pf that is concomitant with bilateral inhibition of POm. The opposing influences of the superior colliculus on Pf and POm are significant, because both these thalamic nuclei innervate the striatum, which is involved in behavioral selection. In view of data indicating that thalamostriatal projections from Pf and other intralaminar nuclei increase the sensitivity of the indirect pathway to corticostriatal inputs (Ding et al., Neuron 67:294-307, 2010), we tested whether POm stimulation might exert an opposing influence on the basal ganglia circuitry. Consistent with POm projections to the dorsolateral striatum (DLS), which is necessary for the expression of sensorimotor habits, we found that POm stimulation activates DLS and causes inhibition of neuronal activity in the lateral part of the substantia nigra pars reticulata, which is a major target of DLS and the direct pathway. These findings are discussed with respect to clinical reports indicating that deep brain stimulation in ZI is effective in reducing the symptoms of Parkinson's disease. PMID- 28988339 TI - Teaching Parents Behavioral Strategies for Autism Spectrum Disorder (ASD): Effects on Stress, Strain, and Competence. AB - We report on parent outcomes from a randomized clinical trial of parent training (PT) versus psychoeducation (PEP) in 180 children with autism spectrum disorder (ASD) and disruptive behavior. We compare the impact of PT and PEP on parent outcomes: Parenting Stress Index (PSI), Parent Sense of Competence (PSOC), and Caregiver Strain Questionnaire (CGSQ). Mixed-effects linear models evaluated differences at weeks 12 and 24, controlling for baseline scores. Parents in PT reported greater improvement than PEP on the PSOC (ES = 0.34), CGSQ (ES = 0.50), and difficult child subdomain of the PSI (ES = 0.44). This is the largest trial assessing PT in ASD on parent outcomes. PT reduces disruptive behavior in children, and improves parental competence while reducing parental stress and parental strain. PMID- 28988340 TI - Inefficacy of autologous bone marrow concentrate in stage three osteonecrosis: a randomized controlled double-blind trial. AB - PURPOSE: The fracture stage of non-traumatic osteonecrosis (ON stage 3) of the femoral head (ONFH) has an unfavourable prognosis frequently requiring total hip replacement (THR). The percentage could be lowered after core decompression. In earlier non-fracture ON stages, implantation of autologous bone marrow aspirate concentrate (BMAC) improved the effect of core decompression. The purpose was to evaluate the effect of BMAC in addition to core decompression in stage 3 ONFH. METHODS: A double blind RCT was conducted comparing two groups: core decompression plus saline injection or core decompression plus BMAC implantation. Both patients and assessors were blinded to the treatment assignments. Evaluations were done at baseline, three, six, 12, and 24 months, including pain (VAS), WOMAC, side-effects, radiological evolution including ARCO subclassifications, together with possible THR requirement. The primary endpoint was the need for THR. The second endpoints included the clinical symptoms such as pain and functional ability and the progression of the ON lesions as well as the appearance of osteoarthritis features (ARCO stage 4). Both groups included 23 hips (19 patients). RESULTS: No differences were found between the groups for THR requirements, clinical tests, and radiological evolution. In both groups, 15/23 hips needed THR. The radiological evolution of the ONFH lesions in term of location, extension, surface collapse, and dome depression was moderate in both groups and was not correlated with the need of THR. CONCLUSIONS: Implantation of BMAC after core decompression did not produce any improvement of the evolution of ONFH stage 3. Level of evidence I. PMID- 28988341 TI - Randomized phase II trial comparing axitinib with the combination of axitinib and lomustine in patients with recurrent glioblastoma. AB - Axitinib is a small molecule tyrosine kinase inhibitor with high affinity and specificity for the family of vascular endothelial growth factor receptors. It has previously demonstrated anti-tumor activity in a small cohort of patients with recurrent glioblastoma (rGB). We conducted a non-comparative randomized phase II clinical trial investigating axitinib monotherapy versus axitinib plus lomustine (LOM) in patients with rGB. Primary endpoint was 6 month progression free survival (6mPFS). Patients who progressed on axitinib-monotherapy were allowed to cross-over. Between August 2011 and July 2015, 79 patients were randomized and initiated axitinib monotherapy (n = 50; AXI) or axitinib plus lomustine (n = 29; AXILOM). Median age was 55y [range 18-80], 50M/28F. Baseline characteristics were well balanced between study arms. Nineteen patients in the AXI-arm crossed-over at the time of progression. Treatment was generally well tolerated. AXILOM patients were at higher risk for grade 3/4 neutropenia (0 vs. 21%) and thrombocytopenia (4 vs. 29%). Best Overall Response Rate (BORR) in the AXI-arm was 28 vs. 38% in the AXILOM-arm. 6mPFS was 26% (95% CI 14-38) versus 17% (95% CI 2-32) for patients treated in the AXI versus AXILOM-arms, respectively. Median overall survival was 29 weeks (95% CI 20-38) in the AXI-arm and 27.4 weeks (95% CI 18.4-36.5) in the AXILOM-arm. MGMT-promoter hypermethylation and steroid treatment at baseline correlated significantly with PFS and OS. We conclude from these results that axitinib improves response rate and progression-free survival in patients with rGB compared to historical controls. There is no indication that upfront combination of axitinib with LOM improves results (European Clinical Trials Database (EudraCT) Study Number: 2011-000900-16). PMID- 28988343 TI - To see and then to act, that is the challenge. PMID- 28988342 TI - Spectrum of outcomes following traumatic brain injury-relationship between functional impairment and health-related quality of life. AB - BACKGROUND: The outcome following traumatic brain injury (TBI) is heterogeneous and poorly defined and physical disability scales like the extended Glasgow Outcome Score (GOSE) while providing valuation information in terms of broad categorisation of outcome are unlikely to capture the full spectrum of deficits. Quality of life questionnaires such as SF-36 are emerging as potential tools to help characterise factors important to patients' recovery. This study assessed the association between physical disability and subjective health rating. The relationship is of value as it may help evaluate the impact of TBI on patients' lives and facilitate the delivery of appropriate neuro-rehabilitation services. METHODS: A single-centre retrospective study was undertaken to assess the relationship between physical outcome as measured by GOSE and quality of life captured by the SF-36 questionnaire. Cronbach's alpha was calculated for each of the eight SF-36 domains to measure internal consistency of the test. Multivariate analysis of variance was conducted to look at the association between GOSE and the physical (PCS) and mental (MCS) component scores on the SF-36. Finally, we performed a generalised linear mixed model (GLMM) to assess the relative contribution of GOSE score, age at the time of trauma, sex and TBI duration towards MCS and PCS rating. RESULTS: There is a statistically significant difference in the MCS and PCS scores based on patients' GOSE scores. The mean scores of the eight SF-36 domains showed significant association with GOSE. GLMM demonstrated that GOSE was the strongest predictor of PCS and MCS. Age was an important variable in the PCS score while time following trauma was a significant predictor of MCS rating. CONCLUSIONS: This study highlights that patients' physical outcome following TBI is a strong predictor of the subjective mental and physical health. Nevertheless, there remains tremendous variability in individual SF-36 scores for each GOSE category, highlighting that additional factors play a role in determining quality of life. PMID- 28988344 TI - How should we manage internal margins in four-dimensional dose assessments? PMID- 28988345 TI - Partial caries removal in deep caries lesions: a 5-year multicenter randomized controlled trial. AB - OBJECTIVE: This multicenter randomized controlled clinical trial aimed to compare the outcomes of stepwise excavation (SW) and partial caries removal (PCR) regarding the maintenance of pulp vitality in deep caries lesions over 5 years. METHODS: At baseline, 299 permanent molars with deep caries lesions were randomly assigned to control or test groups. The control group received the stepwise excavation treatment (SW), while the test group received partial caries removal from the pulpal wall followed by restoration in a single session (PCR). Treatments were conducted in two centers located in the cities of Porto Alegre (South Brazil) and Brasilia (Midwest Brazil). Survival analysis was performed to compare PCR and SW over time (Weibull regression models). The primary outcome of this study was pulp vitality, determined by the combination of the following characteristics: positive response to cold test, negative response to percussion, absence of spontaneous pain, and absence of periapical lesion (radiographic examination). RESULTS: This 5-year study includes data pertaining to 229 teeth: 121 teeth actually examined at the 5-year appointment, and 108 teeth contributed with data collected in previous follow-ups (18 months or 3 years). Survival analysis showed success rates of 80% in PCR group and 56% in SW group (p < 0.001). Failure was significantly associated with treatment [PCR, HR=0.38; 95%CI=0.23-0.63)] and region [South, HR=2.22; 95%CI=1.21-4.08]. CONCLUSION: PCR significantly reduced the occurrence of pulp necrosis when compared with SW. CLINICAL RELEVANCE: This study supports the PCR as a single-visit technique to manage deep caries lesions in permanent teeth. PMID- 28988347 TI - Diagnosing Autism in Adults with Intellectual Disability: Validation of the DiBAS R in an Independent Sample. AB - The study assessed the diagnostic validity of the diagnostic behavioral assessment for autism spectrum disorders-revised (DiBAS-R; 19-item screening scale based on ratings by caregivers) in a clinical sample of 381 adults with ID. Analysis revealed a sensitivity of 0.82 and a specificity of 0.67 in the overall sample (70.3% agreement). Sensitivity (0.79) and specificity (0.84) were balanced in individuals with mild to moderate ID (83.3% agreement), while specificity was lower in individuals with severe to profound ID (sensitivity: 0.83, specificity: 0.34, 51% agreement). The level of ID as well as its interaction with ASD explained a significant proportion of the variance in the DiBAS-R scores. The DiBAS-R is an adequate screening tool, especially in individuals with mild to moderate ID. PMID- 28988346 TI - Lipid environment induces ER stress, TXNIP expression and inflammation in immune cells of individuals with type 2 diabetes. AB - AIMS/HYPOTHESIS: Obesity and type 2 diabetes are concomitant with low-grade inflammation affecting insulin sensitivity and insulin secretion. Recently, the thioredoxin interacting protein (TXNIP) has been implicated in the activation process of the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome. In this study, we aim to determine whether the expression of TXNIP is altered in the circulating immune cells of individuals with type 2 vs type 1 diabetes and whether this can be related to specific causes and consequences of inflammation. METHODS: The expression of TXNIP, inflammatory markers, markers of the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress and enzymes involved in sphingolipid metabolism was quantified by quantitative reverse transcription real-time PCR (qRT-PCR) in peripheral blood mononuclear cells (PBMCs) of 13 non-diabetic individuals, 23 individuals with type 1 diabetes and 81 with type 2 diabetes. A lipidomic analysis on the plasma of 13 non diabetic individuals, 35 individuals with type 1 diabetes and 94 with type 2 diabetes was performed. The effects of ER stress or of specific lipids on TXNIP and inflammatory marker expression were analysed in human monocyte-derived macrophages (HMDMs) and THP-1 cells. RESULTS: The expression of TXNIP and inflammatory and UPR markers was increased in the PBMCs of individuals with type 2 diabetes when compared with non-diabetic individuals or individuals with type 1 diabetes. TXNIP expression was significantly correlated with plasma fasting glucose, plasma triacylglycerol concentrations and specific UPR markers. Induction of ER stress in THP-1 cells or cultured HMDMs led to increased expression of UPR markers, TXNIP, NLRP3 and IL-1beta. Conversely, a chemical chaperone reduced the expression of UPR markers and TXNIP in PBMCs of individuals with type 2 diabetes. The lipidomic plasma analysis revealed an increased concentration of saturated dihydroceramide and sphingomyelin in individuals with type 2 diabetes when compared with non-diabetic individuals and individuals with type 1 diabetes. In addition, the expression of specific enzymes of sphingolipid metabolism, dihydroceramide desaturase 1 and sphingomyelin synthase 1, was increased in the PBMCs of individuals with type 2 diabetes. Palmitate or C2 ceramide induced ER stress in macrophages as well as increased expression of TXNIP, NLRP3 and IL-1beta. CONCLUSIONS/INTERPRETATION: In individuals with type 2 diabetes, circulating immune cells display an inflammatory phenotype that can be linked to ER stress and TXNIP expression. Immune cell ER stress can in turn be linked to the specific exogenous and endogenous lipid environment found in type 2 diabetes. PMID- 28988348 TI - Insight into the neuroendocrine basis of signal evolution: a case study in foot flagging frogs. AB - A hallmark of sexual selection is the evolution of elaborate male sexual signals. Yet, how the physiology of an animal changes to support a new or modified signal is a question that has remained largely unanswered. Androgens are important in regulating male reproductive behavior, therefore, selection for particular signals may drive the evolution of increased androgenic sensitivity in the neuro motor systems underlying their production. Studies of the neuroendocrine mechanisms of anuran sexual signaling provide evidence to support this idea. Here, we highlight two such cases: first, a large body of work in Xenopus frogs demonstrates that sexually dimorphic androgen receptor (AR) expression in the laryngeal nerves and muscles underlies sexually dimorphic vocal behavior, and second, our own work showing that the recent evolution of a hind limb signal (known as the "foot flag") in Staurois parvus is accompanied by a dramatic increase in androgenic sensitivity of the thigh muscles that control limb movement. Together, these examples illustrate that the evolutionary modification or gain of a sexual signal is linked with a novel pattern of AR expression in the tissues that support it. We suggest that such co-evolution of AR expression and sex-specific or species-specific signaling behavior exists across vertebrates. PMID- 28988349 TI - Mastocytosis in Children. AB - PURPOSE OF REVIEW: In this review, we examine the current understanding of the pathogenesis, clinical presentations, diagnostic tools, and treatment options of pediatric mastocytosis as well as the natural history of the disease. RECENT FINDINGS: We discuss the emerging concept of mast cell activation syndrome. Mastocytosis in children presents most commonly as isolated cutaneous lesions and is a relatively rare occurrence with excellent prognosis and spontaneous regression often occurring by adolescence. Systemic mastocytosis with organ system involvement is a more serious condition and is likely to persist into adulthood. PMID- 28988350 TI - Predictors of 30- and 90-day readmission following craniotomy for malignant brain tumors: analysis of nationwide data. AB - Hospital readmissions are a major contributor to increased health care costs and are associated with worse patient outcomes after neurosurgery. We used the newly released Nationwide Readmissions Database (NRD) to describe the association between patient, hospital and payer factors with 30- and 90-day readmission following craniotomy for malignant brain tumor. All adult inpatients undergoing craniotomy for primary and secondary malignant brain tumors in the NRD from 2013 to 2014 were included. We identified all cause readmissions within 30- and 90 days following craniotomy for tumor, excluding scheduled chemotherapeutic procedures. We used univariate and multivariate models to identify patient, hospital and administrative factors associated with readmission. We identified 27,717 admissions for brain tumor craniotomy in 2013-2014, with 3343 (13.2%) 30 day and 5271 (25.7%) 90-day readmissions. In multivariate analysis, patients with Medicaid and Medicare were more likely to be readmitted at 30- and 90-days compared to privately insured patients. Patients with two or more comorbidities were more likely to be readmitted at 30- and 90-days, and patients discharged to skilled nursing facilities or home health care were associated with increased 90 day readmission rates. Finally, hospital procedural volume above the 75th percentile was associated with decreased 90-day readmission rates. Patients treated at high volume hospitals are less likely to be readmitted at 90-days. Insurance type, non-routine discharge and patient comorbidities are predictors of postoperative non-scheduled readmission. Further studies may elucidate potentially modifiable risk factors when attempting to improve outcomes and reduce cost associated with brain tumor surgery. PMID- 28988351 TI - Management of Complex Anterior Shoulder Instability: a Case-Based Approach. AB - PURPOSE OF THE REVIEW: The goal of this review is to provide a guide on surgical decision-making options for complex anterior shoulder instability using a case based approach. RECENT FINDINGS: Arthroscopic Bankart repair is well documented for having successful outcomes in patients with isolated labral tear involvement with minimal bone loss. Latarjet is a generally accepted procedure in patients with 20-30% glenoid bone loss. When bone loss exceeds that which cannot be managed through Latarjet, a range of options exist and are highly dependent upon the extent of osseous deficiency on both the glenoid and humeral sides, surgeon experience, and patient-specific factors. The use of reverse total shoulder arthroplasty for the management of chronic locked shoulder dislocations has been described as a successful management option. Treatment options for complex anterior shoulder instability range widely based on patients' presenting exam, surgical history, amount of glenoid bone loss, size of Hill-Sachs lesion, and surgeon preference. When selecting the appropriate surgical intervention, the treating surgeon must consider the patient history, physical exam, and preoperative imaging along with patient expectations. PMID- 28988352 TI - Is a local sample internationally representative? Reproducibility of four cognitive tests in family dogs across testing sites and breeds. AB - A fundamental precept of the scientific method is reproducibility of methods and results, and there is growing concern over the failure to reproduce significant results. Family dogs have become a favoured species in comparative cognition research, but they may be subject to cognitive differences arising from genetic (breeding lines) or cultural differences (e.g. preferred training methods). Such variation is of concern as it affects the validity and generalisability of experimental results. Despite its importance, this problem has not been specifically addressed to date. Therefore, we aimed to test the influence of three factors on reproducibility: testing site (proximal environment), breed and sex (phenotype). The same experimenter tested cognitive performance by more than 200 dogs in four experiments. Additionally, dogs' performance was tested in an obedience task administered by the owner. Breed of dog and testing site were found to influence the level of performance only mildly, and only in a means-end experiment and the obedience task. Our findings demonstrate that by applying the same test protocols on sufficiently large samples, the reported phenomena in these cognitive tests can be reproduced, but slight differences in performance levels can occur between different samples. Accordingly, we recommend the utilisation of well-described protocols supported by video examples of the whole experimental procedure. Findings should focus on the main outcome variables of the experiments, rather than speculating about the general importance of small or secondary performance outcomes which are more susceptible to random or local noise. PMID- 28988353 TI - When acrocyanosis in intensive care unit is not due to vasopressor support. PMID- 28988355 TI - Updating the Evidence on Functional Capacity Evaluation Methods: A Systematic Review. AB - Objectives To synthesize the evidence on the psychometrics functional capacity evaluation (FCE) methods. Methods A systematic literature search in nine databases. The resulting articles were screened based on predefined in- and exclusion criteria. Two reviewers independently performed this screening. Included studies were appraised based on their methodological quality. Results The search resulted in 20 eligible studies about nine different FCE methods. The Baltimore Therapeutic Equipment work simulator showed a moderate predictive validity. The Ergo-Kit (EK) showed moderate variability and high inter- and intra rater reliability. Low discriminative abilities and high convergent validity were found for the EK. Concurrent validity of the EK and the ERGOS Work Simulator was low to moderate. Moderate to high test-retest, inter- and intra-reliability was found in the Isernhagen Work-Systems (IWS) FCE. The predictive validity of the IWS was low. The physical work performance evaluation (PWPE) showed moderate test retest reliability and moderate to high inter-rater reliability. Low internal and external responsiveness were found for the PWPE, predictive validity was high. The predictive validity of the short-form FCE was also high but need to be further examined on several psychometric properties. Low discriminative and convergent validity were found for the work disability functional assessment battery. The WorkHab showed moderate to high test-retest, inter- and intra-rater reliability. Conclusion Well-known FCE methods have been rigorously studied, but some of the research indicates weaknesses in their reliability and validity. Future research should address how these weaknesses can be overcome. PMID- 28988356 TI - Image-guided treatment of Budd-Chiari syndrome: a giant leap from the past, a small step towards the future. AB - Budd-Chiari syndrome (BCS) is a relatively rare vascular disease characterized by hepatic outflow tract obstruction, and image-guided endovascular treatment, namely percutaneous angioplasty, stenting, and transjugular intrahepatic portosystemic shunt (TIPS), has proven to be effective treatment modalities to alleviate symptoms and markedly improve the prognosis of the disease. Specifically, a step-wise approach is recommended, i.e., angioplasty and stenting are the prioritized choice for patients with membranous obstruction and short length stenosis, whereas TIPS is the option for patients who fail this treatment. Currently, 5-year survival with the step-wise approach is about 75%, and the most promising way to further improve this value is to identify candidates who are at high risk of failing angioplasty, and perform pre-emptive TIPS in these patients. PMID- 28988354 TI - Over-expression of the Arabidopsis formate dehydrogenase in chloroplasts enhances formaldehyde uptake and metabolism in transgenic tobacco leaves. AB - MAIN CONCLUSION: Over-expression of AtFDH controlled by the promoter of Rubisco small subunit in chloroplasts increases formaldehyde uptake and metabolism in tobacco leaves. Our previous study showed that formaldehyde (HCHO) uptake and resistance in tobacco are weaker than in Arabidopsis. Formate dehydrogenase in Arabidopsis (AtFDH) is a key enzyme in HCHO metabolism by oxidation of HCOOH to CO2, which enters the Calvin cycle to be assimilated into glucose. HCHO metabolic mechanism in tobacco differs from that in Arabidopsis. In this study, AtFDH was over-expressed in the chloroplasts of transgenic tobacco using a light inducible promoter. 13C-NMR analysis showed that the carbon flux from H13CHO metabolism was not introduced into the Calvin cycle to produce glucose in transgenic tobacco leaves. However, the over-expression of AtFDH significantly enhanced the HCHO metabolism in transgenic leaves. Consequently, the productions of [4-13C]Asn, [3 13C]Gln, [U-13C]oxalate, and H13COOH were notably greater in transgenic leaves than in non-transformed leaves after treatment with H13CHO. The increased stomatal conductance and aperture in transgenic leaves might be ascribed to the increased yield of oxalate in the guard cells with over-expressed AtFDH in chloroplasts. Accordingly, the transgenic plants exhibited a stronger capacity to absorb gaseous HCHO. Furthermore, the higher proline content in transgenic leaves compared with non-transformed leaves under HCHO stress might be attributable to the excess formate accumulation and Gln production. Consequently, the HCHO induced oxidative stress was reduced in transgenic leaves. PMID- 28988360 TI - Correction to: Challenges in minor TBI and indications for head CT in pediatric TBI-an update. AB - The published version of this article unfortunately contained an error.An error in the Abstract was introduced during corrections stage when a "Conclusion" section appended is from a different article and was not provided from authors. PMID- 28988358 TI - Reliability and validity of the cross-culturally adapted Turkish version of the Core Outcome Measures Index for low back pain. AB - PURPOSE: To produce a cross-culturally adapted and validated Turkish version of The Core Outcome Measure Index (COMI) Back questionnaire. METHODS: Ninety-six Turkish-speaking patients with non-specific low back pain (LBP) were recruited from orthopedic and physical therapy outpatient clinics in a public hospital. They completed a booklet of questionnaires containing Turkish version of COMI, adjectival pain scale, Roland Morris disability questionnaire, European 5 Dimension Questionnaire and brief version of World Health Organization Quality of Life Questionnaire. Within following 7-14 days, 67 patients, reported no or minimal changes in their back pain status, completed the Turkish COMI again to assess reproducibility. RESULTS: Data quality was good with very few missing answers. COMI summary index score displayed 3% floor effects and no ceiling effects. The correlations between the COMI summary index score and each of the full instrument whole scores were found to be excellent to very good (rho = - 0.81 to 0.74). Reliability expressed as intraclass correlation coefficient (ICC) was 0.95 (95% CI 0.91-0.97). Standard error of measurement (SEMagreement) was acceptable at 0.41 and the minimum detectable change (MDC95%) was 1.14. CONCLUSION: Turkish version of the COMI has acceptable psychometric properties. It is a valid and reliable instrument and cross-culturally adapted, in accordance with established guidelines, for the use by Turkish-speaking patients. It can be recommended for use in evaluation of patients with chronic LBP in daily practice, in international multicenter studies and in spine registry systems. PMID- 28988359 TI - Patient-reported outcomes after sacrospinous fixation of vault prolapse with a suturing device: a retrospective national cohort study. AB - INTRODUCTION AND HYPOTHESIS: Innovations in suturing devices have facilitated sacrospinous ligament fixation (SSF) for the correction of vaginal vault prolapse. It is uncertain if outcomes using suturing devices differ from those using a traditional suturing technique. We hypothesize that no difference exists in the efficacy and safety 1 year after SSF for vault prolapse performed with suturing devices or using a traditional technique. The objective was to compare SSF using a suturing device with traditional SSF for the treatment of vault prolapse, regarding symptoms of prolapse recurrence, patient satisfaction, incidence of re-operation, and complications 1 year postoperatively. METHODS: We carried out a retrospective cohort study using register-based national data from 2006 to 2013. The Swedish Quality Register of Gynecological Surgery includes assessments pre-operatively, at hospital admittance, surgery, discharge, and questionnaires at 8 weeks and 1 year after surgery. Demographic variables and surgical methods were included in multivariate logistic regression analyses. RESULTS: In the suturing device group (SDG, n = 353), 71.5% were asymptomatic of recurrence after 1 year compared with 78.7% in the traditional SSF group (TSG, n = 195); risk difference - 7.3% (95%CI -15.2%; 0.7%). Adjusted odds ratio (aOR) for being asymptomatic 1 year postoperatively was 0.56 (95%CI 0.31; 1.02, p = 0.057). Patient satisfaction was similar in SDG and TSG (78.1% vs 78.4%). Reoperation occurred in 7.4% in the SDG compared with 3.6% in the TSG, risk difference 3.8% (95%CI 0.0%; 7.5%), aOR 3.55 (95%CI 1.10; 11.44, p = 0.03). CONCLUSIONS: Patient satisfaction was similar 1 year after SSF, despite symptoms of recurrence being more likely and reoperation more common after using a suturing device compared with a traditional technique. The methods did not differ with regard to surgical complications. PMID- 28988357 TI - The effects of diosmin on aflatoxin-induced liver and kidney damage. AB - Aflatoxin is among the natural toxins that cause serious side effects on living things. Diosmin is also one of the compounds with broad pharmacological effects. In this study, the effects on the oxidant/antioxidant system of 50 mg/kg body weight/day dose of diosmin, aflatoxin (500 MUg/kg body weight/day), and combined aflatoxin (500 MUg/kg body weight/day) plus diosmin (50 mg/kg body weight/day) given to the stomach via catheter female adult Wistar Albino rats is examined. Forty rats were used in the experiment, and these animals were randomly allocated to four equal groups. The test phase lasted 21 days, and blood samples and tissue (liver and kidney) samples were taken after this period was over. Some biochemical parameters (glucose, triglyceride, cholesterol, blood urea nitrogen, creatinine, uric acid, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total protein, albumin) and levels of malondialdehyde, nitric oxide, and 4-hydroxynonenal and activities of superoxide dismutase, catalase, and glutathione peroxidase were analyzed in the samples. The aflatoxin administered over the period indicated a significant increase in levels of malondialdehyde (MDA), nitric oxide (NO), and 4-hydroxynonenal (4-HNE) in all tissues and blood samples. Therewithal, the activity of antioxidant enzymes showed a change in the decreasing direction. Biochemical parameters of the group in which aflatoxin were administered alone changed unfavorably. Parallel effects were also observed in the histopathological findings of this group. The results showed that aflatoxin changed antioxidant/oxidant balance in favor of oxidant and eventually led to lipid peroxidation. Diosmin administration to aflatoxin-treated animals resulted in positive changes in antioxidant enzyme activities while the levels of MDA, NO, and 4-HNE were reduced in all tissues and blood samples examined. Diosmin alleviates the oxidative stress caused by aflatoxin. Similar improvement was observed in biochemical parameters of this group as well as in liver and kidney histopathology. No significant change was observed in the group treated with diosmin alone in terms of the parameters examined and histologic findings. As a result, diosmin may be included in compounds that can be used as a therapeutic and prophylactic agent in the event of the formation of aflatoxin exposure and poisoning in animals. PMID- 28988361 TI - Correction to: Sphenoid dysplasia in neurofibromatosis type 1: a new technique for repair. AB - The published version of this article unfortunately contained an error. All names of the authors have been published incorrectly. Given in this article are the corrected author names. PMID- 28988362 TI - MiR-29b mimics promotes cell apoptosis of smooth muscle cells via targeting on MMP-2. AB - The phenotypic transformation and dysfunctions of vascular smooth muscle cells (SMCs) such as abnormality proliferation and apoptosis are key pathological basis of atherosclerosis. The recent study aimed to detect the role of miR-29b in phenotypic transformation of SMCs. In this study, we investigated the expression level of miR-29b and MMP-2 in acute coronary syndrome (ACS) patients, verified whether MMP-2 is the target gene of miR-29b by luciferase reporter gene system, and explored the role of miR-29b in the viability and apoptosis of SMCs. We found that the plasma level of miR-29b was significantly downregulated to 56% of controls (p < 0.01). The plasma level of MMP-2 in health controls was 34.9 +/- 6.9 ng/mL, and that it significantly increased to 46.2 +/- 13.2 ng/mL in ACS patients. MMP-2 is a target gene of miR-29b. The overexpression of miR-29b significantly downregulated the expression of MMP-2 mRNA and protein. miR-29b mimics inhibited the cell viability of SMCs, and cell apoptosis was significantly enhanced compared with the NC group, especially in the early stage. In the presence of MMP-2 inhibitor SB-3CT, the cell viability and apoptosis of SMC cells were significantly reduced and enhanced, respectively, while the miR-29b inhibited cell viability and -induced cell apoptosis were not significantly changed. Taken together, miR-29b was downregulated in ACS patients. MiR-29 mimics inhibits cell viability and promotes cell apoptosis via directly targeting on MMP 2, which could be a potentially promising therapy target for cardiovascular diseases. PMID- 28988363 TI - Safety of shortened infusion times for combined ipilimumab and nivolumab. AB - BACKGROUND: Combined ipilimumab and nivolumab induces encouraging response rates in patients with unresectable or metastatic melanoma. However, the approved protocol for dual checkpoint inhibition (3 mg/kg ipilimumab over 90 min and 1 mg/kg nivolumab over 60 min) is time-intensive and several trials have shown that both single agents can be safely administered at faster infusion rates. AIM: To investigate whether combined checkpoint inhibition with 3 mg/kg ipilimumab and 1 mg/kg nivolumab can be safely administered over 30 min per agent. PATIENTS AND METHODS: We reviewed the rate of infusion-related reactions (IRRs) in the first 12 months of our single-institution experience using shortened infusion times for combined checkpoint inhibition with ipilimumab and nivolumab. RESULTS: Between May 24, 2016 and June 10, 2017, a total of 46 melanoma patients received 100 shortened cycles of combined 3 mg/kg ipilimumab and 1 mg/kg nivolumab. One patient (2.2%; 1/46) had a questionable reaction after administration of 1 mg/kg nivolumab over 30 min, but none of the other patients had a bona fide IRR. CONCLUSIONS: Shortened infusion times for combined ipilimumab and nivolumab treatment are safe, thereby facilitating a more efficient use of outpatient facilities and enhancing patient's convenience. PMID- 28988364 TI - Genetic parameters for growth performance, fillet traits, and fat percentage of male Nile tilapia (Oreochromis niloticus). AB - Improvement of fillet traits and flesh quality attributes are of great interest in farmed tilapia and other aquaculture species. The main objective of this study was to estimate genetic parameters for fillet traits (fillet weight and fillet yield) and the fat content of fillets from 1136 males combined with 2585 data records on growth traits (body weight at 290 days, weight at slaughter, and daily weight gain) of 1485 males and 1100 females from a third generation of the Aquaamerica tilapia strain. Different models were tested for each trait, and the best models were used to estimate genetic parameters for the fat content, fillet, and growth traits. Genetic and phenotypic correlations were estimated using two trait animal models. The heritability estimates were moderate for the fat content of fillets and fillet yield (0.2-0.32) and slightly higher for body weight at slaughter (0.41). The genetic correlation between fillet yield and fat was significant (0.6), but the genetic correlations were not significant between body weight and fillet yield, body weight and fat content, daily weight gain and fillet yield, and daily weight gain and fat content (- 0.032, - 0.1, - 0.09, and 0.4, respectively). Based on the genetic correlation estimates, it is unlikely that changes in fillet yield and fat content will occur when using growth performance as a selection criterion, but indirect changes may be expected in fat content if selecting for higher fillet yield. PMID- 28988365 TI - Global radiological score for femoral cementless revision stem. AB - PURPOSE: The purpose of this study was to evaluate the outcomes of total hip arthroplasty (THA) revision with cementless stems using a numeric global radiological score (GRxS) that summarizes two previously validated scores: secondary bone stock (SBS) and osseointegration-secondary stability (O-SS). METHOD: One hundred fifty cases of THA were evaluated at a mean follow-up of 6.5 +/- 3.7 years. The GRxS combines the SBS, which evaluated cortical bone thickness, bone density and bone defects in each Gruen zone and the O-SS, which evaluated the location and extent of a single radiolucent line. To calculate the GRxS, the SBS and O-SS were each expressed on a 10-point scale and given equal weighing. The final result was a number out of 20. The GRxS was used to assign a radiological grade to each THA case: very good (20), good (18-15), average (13 12), or poor (<= 10). The numerical mean (Nm) was calculated for each grade. The inter- and intra-observer reproducibility was evaluated. RESULTS: The inter observer reproducibility was good (0.8) and the intra-observer reproducibility was very good (0.9). The GRxS was considered very good in 46 cases (Nm 20), good in 57 cases (Nm 16.6), average in 25 cases and poor in 22 cases. There was a significant relationship between the GRxS and the Harris Hip and Postel Merle d'Aubigne scores (p < 0.0001), and the initial bone stock (p = 0.0001). CONCLUSIONS: The GRxS is reliable and reproducible. This information can be used by surgeons to adapt the surgical technique to bone characteristics (especially during revision cases) and to compare the outcomes of different implant designs. PMID- 28988366 TI - Anxiety and ASD: Current Progress and Ongoing Challenges. AB - Symptoms of anxiety add significant burden to many autistic individuals and their loved ones. There is an urgent need for better understanding of the unique underlying mechanisms of anxiety in ASD, and for the development of more specific assessment methods and treatment recommendations. This special issue brings together 24 articles grouped into three themes; mechanisms, measurement, and intervention. The result is a review of current anxiety research in ASD that is both broad and deep. Key themes include recognition of the importance individual differences in aetiology and presentation of anxiety in ASD, the need for a more nuanced understanding of the interactions between anxiety and characteristics of ASD and the need to develop appropriately adapted treatments. PMID- 28988367 TI - Neonatal diabetes in a patient with IPEX syndrome: an attempt at balancing insulin therapy. PMID- 28988368 TI - Post-embryonic development of the Malpighian tubules in Apis mellifera (Hymenoptera) workers: morphology, remodeling, apoptosis, and cell proliferation. AB - The honeybee Apis mellifera has ecological and economic importance; however, it experiences a population decline, perhaps due to exposure to toxic compounds, which are excreted by Malpighian tubules. During metamorphosis of A. mellifera, the Malpighian tubules degenerate and are formed de novo. The objective of this work was to verify the cellular events of the Malpighian tubule renewal in the metamorphosis, which are the gradual steps of cell remodeling, determining different cell types and their roles in the excretory activity in A. mellifera. Immunofluorescence and ultrastructural analyses showed that the cells of the larval Malpighian tubules degenerate by apoptosis and autophagy, and the new Malpighian tubules are formed by cell proliferation. The ultrastructure of the cells in the Malpighian tubules suggest that cellular remodeling only occurs from dark-brown-eyed pupae, indicating the onset of excretion activity in pupal Malpighian tubules. In adult forager workers, two cell types occur in the Malpighian tubules, one with ultrastructural features (abundance of mitochondria, vacuoles, microvilli, and narrow basal labyrinth) for primary urine production and another cell type with dilated basal labyrinth, long microvilli, and absence of spherocrystals, which suggest a role in primary urine re-absorpotion. This study suggests that during the metamorphosis, Malpighian tubules are non functional until the light-brown-eyed pupae, indicating that A. mellifera may be more vulnerable to toxic compounds at early pupal stages. In addition, cell ultrastructure suggests that the Malpighian tubules may be functional from dark brown-eyed pupae and acquire greater complexity in the forager worker bee. PMID- 28988369 TI - Retention of molars after root-resective therapy: a retrospective evaluation of up to 30 years. AB - OBJECTIVES: Long-term retention of teeth and especially molars in function is the ultimate goal of periodontal therapy. Root-resective therapy is a treatment option for molars with advanced furcation involvement, which has been questioned because of the heterogenous success rates published in literature. This study aimed to evaluate long-term results of root-resective treatment over a period of up to 30 years. METHODS: In this retrospective cohort, 90 root-resected molars in 69 patients were examined for 4-30 years (14.7 +/- 6.8 years). The complete treatment sequence was performed by one of the authors in a general dental practice. RESULTS: Overall cumulative survival rate was 90.6% after 10 years, but then decreased considerably. Molars after root resection had a median survival time of 20 years. The incidence of endodontic complications leading to tooth extraction was only 26.7%, 50% were lost due to periodontal problems, and 16.7% because of caries. Mandibular molars had a significantly lower relative risk of loss than molars in the maxilla (HR 0.31, 95% CI 0.1-0.91, p = 0.033). Mandibular molars showed a survival probability of almost 80% even 20 years after root resection. CONCLUSION: Root-resective therapy is a predictable treatment option, when care is administered at each phase of therapy. CLINICAL RELEVANCE: This study provides important information about what is possible in daily practice under the outlines of public health care, when care is administered at each phase of resective therapy. PMID- 28988370 TI - Morphologic characteristics of macroscopic peritoneal finding in patients with peritoneal dialysis. AB - Peritoneal dialysis (PD) has been an attractive treatment for end-stage kidney disease. Long-term exposure to the PD solution creates functional and morphological alterations, and these alterations diminish the efficacy of PD. It is important to establish an evaluation of the changes in PD patients and strategies for the prevention of PD damage and encapsulating peritoneal sclerosis (EPS). We determined the relationship between clinical findings and macroscopic morphological findings by laparoscopy in patients receiving PD. Macroscopic intraperitoneal findings were recorded at the PD catheter removal in 23 PD patients. We examined macroscopic morphological findings such as fibrin deposition, peritoneal turbidity, vasculopathy, adhesion and calcification in both parietal and visceral peritoneum of upper and lower peritoneal cavities, and assessed the score semi-quantitatively. We then evaluated the relationship between the morphological score and clinical findings, especially observational parts and findings in EPS patients. The total macroscopic score increased with PD duration. Peritoneal turbidity, fibrin deposition, and calcification were observed in the whole peritoneal cavity. Scores of fibrin deposition, turbidity, and calcification increased with PD duration. Vasculopathy in the parietal peritoneum was more serious compared with that in the visceral peritoneum, but there was no difference in the vasculopathy between the upper and lower areas. A characteristic of the macroscopic findings in EPS patients was peritoneal calcification in this study. It appears that macroscopic findings using laparoscopy is significant in evaluating the degree of the peritoneum damage and predicting EPS development. PMID- 28988371 TI - Potential imaging findings following assisted reproduction: complications and clinical implications. AB - Recent rapid advances in assisted reproduction (ART) have led to global increase in usage of in vitro fertilization. This in turn has resulted in clinicians and imaging specialists encountering increase in complications associated with ART. The specialists dealing with infertility should be aware of potential complications associated with ART. Early diagnosis of these problems is based on clinician's suspicion and radiologist's awareness of these complications. Many of these conditions may be life threatening. Hence, early diagnosis and treatment of these complications can safeguard the fetal and maternal health. PMID- 28988372 TI - Ultra-low dose of intravitreal bevacizumab in retinopathy of prematurity. AB - AIM: We aimed to investigate the effectivity of the 0.0625 mg dose of bevacizumab in patients with retinopathy of prematurity (ROP) and compare the results with 0.625 mg dose of intravitreal bevacizumab (IVB) injection. METHODS: The medical records of the patients with type 1 ROP who received IVB monotherapy were retrospectively reviewed. Demographic and clinical characteristics of the patients were recorded. The patients were classified into two groups with respect to received dose of bevacizumab as follows: group F (n = 46) (full dose of bevacizumab-0.625 mg/0.025 ml) and group L (n = 45) (low dose (one tenth) of bevacizumab-0.0625 mg/0.025 ml). RESULTS: Both treatment dose regimens have similar outcomes. Moreover, the mean retinal vascularization time seemed to be significantly higher in group F compared to group L, 168 +/- 65 and 97 +/- 29 days, respectively (p < 0.001). Disappearance of plus sign is observed earlier in group F (2.45 +/- 1.7 vs 3.66 +/- 2.46 days, respectively, p = 0.03). CONCLUSIONS: The low dose (0.0625 mg) of IVB treatment was effective as full (0.625 mg) dose in ROP treatment. Moreover, our results showed that low-dose treatment might provide faster retinal vascularization than the regular used dose. On the other hand, disappearance of the plus sign takes longer time in patients treated with low dose compared to eyes treated with full dose of IVB that should be taken into account. PMID- 28988373 TI - Lithium Treatment Aggregates the Adverse Effects on Erythrocytes Subjected to Arsenic Exposure. AB - The present study was designed to investigate the effects of lithium treatment on red blood cells which were given arsenic exposure. Long-term lithium therapy is being extensively used for the treatment of bipolar disorders. Arsenic is a group I carcinogen and a major toxic pollutant in drinking water that affects millions of people worldwide. Male SD rats were segregated into four groups, viz. normal control, lithium treated, arsenic treated, and lithium + arsenic treated. Lithium was supplemented as lithium carbonate at a dose level of 1.1 g/kg diet for a period of 8 weeks. Arsenic was given in the form of sodium arsenite at a dose level of 100 ppm in drinking water, ad libitum, for the same period. Lysates of red blood cells were used to investigate the effects of lithium and arsenic treatments on anti-oxidant enzymes, reduced glutathione (GSH), and lipid peroxidation (LPO) levels. Various hematological parameters, activities of Na+ K+ ATPase and delta-aminolevulinic acid dehydratase (delta-ALAD) were also assessed. A significant reduction was observed in the activities of antioxidant enzymes, GSH levels, total erythrocyte counts, Na+ K+ ATPase, and ALAD enzyme activities in lysates of red blood cells when exposed either to lithium or arsenic. In addition, a significant increase in the levels of malondialdehyde (MDA), lymphocytes, neutrophils, and total leukocytes was also observed following lithium as well as arsenic treatments. However, when arsenic-treated rats were subjected to lithium treatment, a pronounced alteration was noticed in all the above parameters. Therefore, we conclude that lithium supplementation to the arsenic-treated rats enhances the adverse effects on red blood cells and therefore use of lithium may not be medicated to patients who are vulnerable to arsenic exposure through drinking water. It can also be inferred that adverse effects of lithium therapy may get aggravated in patients thriving in the arsenic contaminated area. PMID- 28988374 TI - Temporal Processing Instability with Millisecond Accuracy is a Cardinal Feature of Sensorimotor Impairments in Autism Spectrum Disorder: Analysis Using the Synchronized Finger-Tapping Task. AB - To identify a specific sensorimotor impairment feature of autism spectrum disorder (ASD), we focused on temporal processing with millisecond accuracy. A synchronized finger-tapping task was used to characterize temporal processing in individuals with ASD as compared to typically developing (TD) individuals. We found that individuals with ASD showed more variability in temporal processing parameters than TD individuals. In addition, temporal processing instability was related to altered motor performance. Further, receiver operating characteristic (ROC) curve analyses indicated that altered temporal processing can be useful for distinguishing between individuals with and without ASD. These results suggest that instability of temporal processing with millisecond accuracy is a fundamental feature of sensorimotor impairments in ASD. PMID- 28988375 TI - Long-Term Care Needs in the Context of Poverty and Population Aging: the Case of Older Persons in Myanmar. AB - Myanmar is one of the poorest and least healthy countries in Southeast Asia. As elsewhere in the region, population aging is occurring. Yet the government welfare and health systems have done little to address the long-term care (LTC) needs of the increasing number of older persons thus leaving families to cope on their own. Our study, based on the 2012 Myanmar Aging Survey, documents the LTC needs of persons aged 60 and older and how they are met within the context of the family. Nearly 40% of persons in their early 60s and 90% of those 80 and older reported at least one physical difficulty. Spouses and children constitute the mainstay of the financial and instrumental support of elderly including those with LTC needs. Nearly two-thirds of older persons reported receiving assistance with daily living activities. More than three quarters coreside with children, a living arrangement that in turn is strongly associated with receiving regular assistance in daily living. Daughters represent almost half and spouses, primarily wives, one-fourth of primary caregivers. Unmet need for care as well as inadequate care decline almost linearly with increased household wealth. Thus elderly in the poorest households are most likely to experience gaps in LTC. Given mounting concerns regarding health disparities among Myanmar's population, this pattern of inequality clearly needs to be recognized and addressed. This needs attention now rather than later given that reduced family size and increased migration pose additional challenges for family caregiving of frail elderly in the coming decades. PMID- 28988376 TI - Differential diagnosis of the finger swelling on Pythagoras in the "School of Athens" (1509-1511) by Raphael (1483-1520). PMID- 28988378 TI - Hospital volume and group expertise in newly diagnosed glioblastoma management. PMID- 28988377 TI - Phase I study of sorafenib and tipifarnib for recurrent glioblastoma: NABTC 05 02. AB - Recurrent glioblastoma (GBM) has a very low 6-month progression free survival (PFS) with currently available treatments. Combination chemotherapy to target multiple cell signaling pathways is currently being investigated in order to improve prognosis for recurrent disease. The purpose of this phase I study was to determine the maximum tolerated dose (MTD) for the combination of tipifarnib and sorafenib for the treatment of recurrent GBM. Patients with pathologically proven WHO grade IV GBM and radiographically proven tumor recurrence were eligible for this study. Treatments included sorafenib at twice daily and escalating dosages of tipifarnib. Dose-limiting toxicity (DLT) was determined over the first 28-days of treatments, and the MTD was determined in a 3 + 3 study design. We enrolled 24 patients, and 21 patients completed the MTD period. The study was stopped early with no MTD determination for excessive toxicities. The last dose level reached was sorafenib at 200 mg twice a day and tipifarnib 100 mg twice a day on an alternating week schedule. The DLTs included diarrhea, lipase elevation, hypophosphatemia, and arthralgia. The combination of sorafenib and tipifarnib has excessive toxicities and full single agent dosages could not be achieved in combination. PMID- 28988380 TI - Tumor-infiltrating immune cells as potential biomarkers predicting response to treatment and survival in patients with metastatic melanoma receiving ipilimumab therapy. AB - Monoclonal antibodies targeting immune checkpoints are gaining ground in the treatment of melanoma and other cancers, and considerable effort is made to identify biomarkers predicting the efficacy of these therapies. Our retrospective study was performed on surgical tissue samples (52 lymph nodes and 34 cutaneous/subcutaneous metastases) from 30 patients with metastatic melanoma treated with ipilimumab. Using a panel of 11 antibodies against different immune cell types, intratumoral immune cell densities were determined and evaluated in relation to response to ipilimumab treatment and disease outcome. For most markers studied, median immune cell densities were at least two times higher in lymph node metastases compared to skin/subcutaneous ones; therefore, the prognostic and predictive associations of immune cell infiltration were evaluated separately in the two groups of metastases as well as in all samples as a whole. Higher prevalence of several immune cell types was seen in lymph node metastases of the responders compared to non-responders, particularly FOXP3+ cells and CD8+ T lymphocytes. In subcutaneous or cutaneous metastases, on the other hand, significant difference could be observed only in the case of CD16 and CD68. Associations of labeled cell densities with survival were also found for most cell types studied in nodal metastases, and for CD16+ and CD68+ cells in skin/s.c. metastatic cases. Our results corroborate the previous findings suggesting an association between an immunologically active tumor microenvironment and response to ipilimumab treatment, and propose new potential biomarkers for predicting treatment efficacy and disease outcome. PMID- 28988379 TI - Iron and iron oxide nanoparticles are highly toxic to Culex quinquefasciatus with little non-target effects on larvivorous fishes. AB - The control of filariasis vectors has been enhanced in several areas, but there are main challenges, including increasing resistance to insecticides and lack of cheap and eco-friendly products. The toxicity of iron (Fe0) and iron oxide (Fe2O3) nanoparticles has been scarcely investigated yet. We studied the larvicidal and pupicidal activity of Fe0 and Fe2O3 nanoparticles against Culex quinquefasciatus. Fe0 and Fe2O3 nanoparticles produced by green (using a Ficus natalensis aqueous extract) and chemical nanosynthesis, respectively, were analyzed by UV-Vis spectrophotometry, FT-IR spectroscopy, XRD analysis, SEM, and EDX assays. In larvicidal and pupicidal experiments on Cx. quinquefasciatus, LC50 of Fe0 nanoparticles ranged from 20.9 (I instar larvae) to 43.7 ppm (pupae) and from 4.5 (I) to 22.1 ppm (pupae) for Fe2O3 nanoparticles synthesized chemically. Furthermore, the predation efficiency of the guppy fish, Poecilia reticulata, after a single treatment with sub-lethal doses of Fe0 and Fe2O3 nanoparticles was magnified. Overall, this work provides new insights about the toxicity of Fe0 and Fe2O3 nanoparticles against mosquito vectors; we suggested that green and chemical fabricated nano-iron may be considered to develop novel and effective pesticides. PMID- 28988381 TI - Response to the letter from Dr. Veerman and colleagues. PMID- 28988382 TI - Does time of surgery and complication have any correlation in the management of hip fracture in elderly and can early surgery affect the outcome? AB - OBJECTIVE: Hip fractures in the elderly are usually associated with a high rate of morbidity and mortality and affect quality of life. On review of published data, the current guidelines in the literature indicate that early surgery should be performed within 24 h of injury because it is associated with better functional outcomes and lower rates of perioperative complications and mortality. The aim of this study was to evaluate whether any correlation exists between early surgical intervention and functional outcomes. METHODS: In a retrospective study, we analyzed the records between January 2010 and December 2016 and 550 elderly patients between the age group of 65-95 were included. RESULTS: The results of early surgery were promising, 451 (82%) patients did not have any complication, 42 (7.6%) has developed bed sore, 23 (4%) developed a hospital acquired infection, 13 (2.3%) developed wound infection, 08 (1.4%) developed DVT, 04 (0.7%) developed implant failure, and 09 (01%) died of some or other complications. CONCLUSION: Still, there is conflicting evidence in the published data that early surgery would improve mortality and function. However, early surgery definitively improves outcome and reduces morbidity, bed sores, infection, and the length of hospital stay could be improved by reducing the waiting time of hip surgery following fracture. We concluded that it is beneficial to the elderly patients to receive surgical treatment as early as possible. PMID- 28988384 TI - Language Barriers Impact Access to Services for Children with Autism Spectrum Disorders. AB - Racial and ethnic disparities in accessing health care have been described in children with autism spectrum disorder (ASD). In a retrospective chart review of 152 children with ASD, children of parents whose primary language was English were significantly more likely to have both social skills and communication goals within their individualized education plan (IEP) compared to children of parents whose primary language was not English. Additionally, children of primary English speakers received significantly more hours of direct services from their state disability program. After controlling for demographic covariates, findings suggest that language barriers may negatively affect parents' abilities to access health care services for their child with ASD. Acculturation factors must therefore be considered when analyzing disparities in autism. PMID- 28988383 TI - Diversity of free-living amoebae in soils and their associated human opportunistic bacteria. AB - Free-living amoebae (FLA) are ubiquitous protozoa found worldwide in the environment. They feed by phagocytosis on various microorganisms. However, some bacteria, i.e., amoebae-resistant bacteria (ARB) or bacterial endocytobionts, can resist phagocytosis and even multiply inside FLA. This study investigated the diversity of culturable FLA in various soils from agricultural and mining sites and their bacterial endocytobionts. FLA were cultured on non-nutrient agar with alive Escherichia coli and identified by PCR and sequencing. Amoebae were lysed and bacterial endocytobionts were cultured on TSA 1/10 and Drigalski medium. Bacterial isolates were identified by PCR and 16S rDNA sequencing and characterized for their antibiotic resistance properties. To measure bacterial virulence, the amoebal model Dictyostelium discoideum was used. The analysis of FLA diversity showed that Tetramitus was the most prevalent genus in agricultural soil from Burkina Faso (73%) and garden soil from Vietnam (42%) while Naegleria and Acanthamoeba were dominant genera in mining soil from Vietnam (55%) and French alpine soil (77%). Some genera were only present in one out of the four soils analyzed. The bacterial endocytobiont included Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. Human opportunistic pathogens identified as Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Burkholderia cepacia were found associated with amoebae including Micriamoeba, Tetramitus, Willaertia, or Acanthamoeba. Some of these bacteria showed various antibiotic resistance phenotypes and were virulent. Our study confirms that the occurrence of these opportunistic bacteria with FLA in soils may be important for the survival, multiplication, and spread of pathogens in the environment. PMID- 28988385 TI - Adapting current model with field data of related performance reference compounds in passive samplers to accurately monitor hydrophobic organic compounds in aqueous media. AB - Performance reference compounds (PRCs) are neutral organic compounds, introduced in a passive sampler prior deployment for the assessment of in situ sampling rate. In this study, evaluation of in situ sampling rates of 16 13C-PAH-PRCs with moderate and high hydrophobicity was established to provide an overall correction factor for variations in virtual organism (VO) uptake rates of the analytes of interest. In situ sampling rate was compared to an empirical model during sampling campaign in 2011 with VO in 12 different sites along the Three Gorges Reservoir (TGR) in China. A discrepancy was observed for high hydrophobic compounds with log K ow ranging from 5.18 to 6.63 where SigmaPAH concentration in TGR from Huckins model (305,624 pg/L) was resulted to be roughly 2-fold higher than the alternative procedure (182,292 pg/L). A relationship between in situ sampling rates of the 16 13C-PAH-PRCs (Rs, PRC ) and log K ow was set up to allow then calculation of analyte sampling rate Rs analyte (N) of various organic pollutants with log K ow <= 6.63. PMID- 28988386 TI - Perspectives on medicinal properties of natural phenolic monoterpenoids and their hybrids. AB - Carvacrol, thymol and eugenol belong to a class of naturally presenting phenols with a ten-carbon unit, which are present in essential oils of many plants. These versatile molecules are incorporated as useful ingredients in many food products and find applications in agricultural, pharmaceutical, fragrance, cosmetic, flavor and other industries. They are wide ranging of biological and pharmaceutical activities: anti-inflammatory, antimicrobial, analgesic, anticancer and antioxidant. This review summarizes pharmacological and medicinal activities of these phytochemicals and their synthetic hybrids. PMID- 28988388 TI - SPICODYN: A Toolbox for the Analysis of Neuronal Network Dynamics and Connectivity from Multi-Site Spike Signal Recordings. AB - We implemented an automated and efficient open-source software for the analysis of multi-site neuronal spike signals. The software package, named SPICODYN, has been developed as a standalone windows GUI application, using C# programming language with Microsoft Visual Studio based on .NET framework 4.5 development environment. Accepted input data formats are HDF5, level 5 MAT and text files, containing recorded or generated time series spike signals data. SPICODYN processes such electrophysiological signals focusing on: spiking and bursting dynamics and functional-effective connectivity analysis. In particular, for inferring network connectivity, a new implementation of the transfer entropy method is presented dealing with multiple time delays (temporal extension) and with multiple binary patterns (high order extension). SPICODYN is specifically tailored to process data coming from different Multi-Electrode Arrays setups, guarantying, in those specific cases, automated processing. The optimized implementation of the Delayed Transfer Entropy and the High-Order Transfer Entropy algorithms, allows performing accurate and rapid analysis on multiple spike trains from thousands of electrodes. PMID- 28988387 TI - Targeting tumor-associated macrophages by anti-tumor Chinese materia medica. AB - Tumor-associated macrophages (TAMs) play a key role in all stages of tumorigenesis and tumor progression. TAMs secrete different kinds of cytokines, chemokines, and enzymes to affect the progression, metastasis, and resistance to therapy depending on their state of reprogramming. Therapeutic benefit in targeting TAMs suggests that macrophages are attractive targets for cancer treatment. Chinese materia medica (CMM) is an important approach for treating cancer in China and in the Asian region. According to the theory of Chinese medicine (CM) and its practice, some prescriptions of CM regulate the body's internal environment possibly including the remodeling the tumor microenvironment (TME). Here we briefly summarize the pivotal effects of TAMs in shaping the TME and promoting tumorigenesis, invasion, metastasis and immunosuppression. Furthermore, we illustrate the effects and mechanisms of CMM targeting TAMs in antitumor therapy. Finally, we reveal the CMM's dual-regulatory and multi targeting functions on regulating TAMs, and hopefully, provide the theoretical basis for CMM clinical practice related to cancer therapy. PMID- 28988389 TI - Treatment-Free Remission: a New Therapeutic Goal in Chronic Myelogenous Leukemia. AB - PURPOSE OF REVIEW: Chronic myelogenous leukemia (CML) is a chronic myeloproliferative neoplasm characterized by the presence of Philadelphia chromosome [t(9:22)] leading to the presence of pathognomonic fusion gene product, BCR-ABL1. This leads to constitutive activation of ABL1 kinase. CML was a difficult-to-treat illness until the advent of small molecule tyrosine kinase inhibitor (TKI), imatinib which revolutionized therapy of CML. Since then, multiple second- and third-generation TKIs have been formulated which have proven effective and has led to marked improvement in survival. In this article, we review currently available data on possibility of holding TKI therapy in patients in deep remission [treatment-free remission (TFR)] and safety of this approach. RECENT FINDINGS: As CML treatment has become more effective, new questions have emerged, most important being whether the treatment with TKIs can ever be stopped. This is especially relevant in patient experiencing side effects from therapy or who may be subject to increased health risks due to treatment. There is now evidence that some CML patients who have achieved stable deep molecular response can safely stop TKI. Furthermore, patients can safely re-establish remission after restarting their TKI therapy in the situation of relapse. CML is highly treatable disease, but the treatment has untoward physical and socioeconomic consequences. The idea of TFR is hence attractive. There is a growing body of evidence that some CML patients who have achieved stable deep molecular response can safely stop TKI. PMID- 28988390 TI - Topographic distribution of brain iron deposition and small cerebrovascular lesions in amyotrophic lateral sclerosis and in frontotemporal lobar degeneration: a post-mortem 7.0-tesla magnetic resonance imaging study with neuropathological correlates. AB - Amyotrophic lateral sclerosis (ALS) is associated with frontotemporal lobar degeneration (FTLD) in 15% of the cases. A neuropathological continuity between ALS and FTLD-TDP is suspected. The present post-mortem 7.0-tesla magnetic resonance imaging (MRI) study compares the topographic distribution of iron (Fe) deposition and the incidence of small cerebrovascular lesions in ALS and in FTLD brains. Seventy-eight post-mortem brains underwent 7.0-tesla MRI. The patients consisted of 12 with ALS, 38 with FTLD, and 28 controls. Three ALS brains had minor FTLD features. Three coronal sections of a cerebral hemisphere were submitted to T2 and T2* MRI sequences. The amount of Fe deposition in the deep brain structures and the number of small cerebrovascular lesions was determined in ALS and the subtypes of FTLD compared to control brains, with neuropathological correlates. A significant increase of Fe deposition was observed in the claustrum, caudate nucleus, globus pallidus, thalamus, and subthalamic nucleus of the FTLD-FUS and FTLD-TDP groups, while in the ALS one, the Fe increase was only observed in the caudate and the subthalamic nuclei. White matter changes were only significantly more severe in the FTLD compared to those in ALS and in controls brains. Cortical micro-bleeds were increased in the frontal and temporal lobes of FTLD as well as of ALS brains compared to controls. Cortical micro-infarcts were, on the other hand, more frequent in the control compared to the ALS and FTLD groups. The present study supports the assumption of a neuropathological continuity between ALS and FTLD and illustrates the favourable vascular risk profile in these diseases. PMID- 28988392 TI - A guide for endometrial cancer cell lines functional assays using the measurements of electronic impedance. AB - Endometrial cancer cell lines are critical tools to investigate the molecular mechanism of tumorigenesis using the end point cell-based assay such as proliferation, cytotoxicity, apoptosis, anoikis or migration and invasion. The proper assay optimization and performance is essential for physiologically relevant results interpretation. In this study we use label-free real-time cell analysis platform (xCELLigence) to optimize growing conditions for proliferation and migration experiments of two types of endometrial cancer cell lines HEC-1-B, HEC-1-A, KLE, and Ishikawa. Profiling of cell lines by cell index measurement in proliferation and migration experiments was performed. Our experimental approach allowed us to monitor particular stage of the cell growth, to see the relation between seeding density and dynamic cell growth as well as to choose the optimal serum concentration as chemoattractant in migration experiment. The highest rate of proliferation was shown for Ishikawa cells. The rapid pace of cellular migration was observed in case of KLE and HEC-1-B cells as compared to weak migratory activity of Ishikawa cells. The cell index that reflects the cell status characterized real-time cytological profile of each analyzed cell line. These cell profiles were crucial for better planning the classical end-point assays used in further research. PMID- 28988391 TI - Transcriptional profiling of cork oak phellogenic cells isolated by laser microdissection. AB - MAIN CONCLUSION: The phenylpropanoid pathway impacts the cork quality development. In cork of bad quality, the flavonoid route is favored, whereas in good quality, cork lignin and suberin production prevails. Cork oaks develop a thick cork tissue as a protective shield that results of the continuous activity of a secondary meristem, the cork cambium, or phellogen. Most studies applied to developmental processes do not consider the cell types from which the samples were extracted. Here, laser microdissection (LM) coupled with transcript profiling using RNA sequencing (454 pyrosequencing) was applied to phellogen cells of trees producing low- and good quality cork. Functional annotation and functional enrichment analyses showed that stress-related genes are enriched in samples extracted from trees producing good quality cork (GQC). This process is under tight transcriptional (transcription factors, kinases) regulation and also hormonal control involving ABA, ethylene, and auxins. The phellogen cells collected from trees producing bad quality cork (BQC) show a consistent up regulation of genes belonging to the flavonoid pathway as a response to stress. They also display a different modulation of cell wall genes resulting into a thinner cork layer, i.e., less meristematic activity. Based on the analysis of the phenylpropanoid pathway regulating genes, in GQC, the synthesis of lignin and suberin is promoted, whereas in BQC, the same pathway favors the biosynthesis of free phenolic compounds. This study provided new insights of how cell-specific gene expression can determine tissue and organ morphology and physiology and identified robust candidate genes that can be used in breeding programs aiming at improving cork quality. PMID- 28988393 TI - Sexual function in adolescents and young adults diagnosed with cancer: A systematic review. AB - PURPOSE: The purpose of this systematic review was to identify, with supporting evidence, the impact of cancer and its treatment on the sexual function of adolescents and young adults. METHODS: PubMed, CINAHL, and PsycINFO articles were searched for relevant studies published in English. Fifteen studies, 13 quantitative and two qualitative, were included in this review. RESULTS: Results indicated that cancer during the adolescent and young adult period has a significant negative impact on certain domains of sexual function in both men and women. CONCLUSIONS: Among adolescent and young adult males, there is evidence that cancer has detrimental effects on erection, ejaculation, and orgasm. Among adolescent and young adult females, cancer is associated with decreased desire, but there appear to be mixed findings with respect to arousal, orgasm, and satisfaction. Directions for future research are discussed. IMPLICATIONS FOR CANCER SURVIVORS: A better understanding of the effects of cancer and its treatment during adolescence and young adulthood on sexual function could increase attention paid to sexual health in oncology settings and lead to improved psychosexual services for this population. PMID- 28988394 TI - Desert amphibian selection of arid land breeding habitat undermines reproductive effort. AB - Understanding how animals select habitat is important for understanding how to better conserve those species. As droughts become more frequent and water availability declines in many systems, understanding selection of water sources becomes even more important for conservation. Tinajas and anthropogenic catchments are critical ephemeral breeding sites for Sonoran Desert anurans. Tadpoles have been documented in both water types even though anthropogenic catchments can contain very high concentrations of ammonia. We currently do not know how amphibians are selecting breeding habitat. We tested three hypotheses of habitat selection based on resource quality, resource quality and territoriality, and proximity of water site to other water sites. Male Anaxyrus punctatus called from all sites regardless of habitat quality or male quality; however, they were found more often at sites within 2 km of other sites. This suggests that male desert anurans are selecting close breeding habitat regardless of quality for breeding, indicating ammoniated sites are likely either population sinks or ecological traps. Consequently, adding anthropogenic water sites, without managing to reduce ammonia, will provide low quality habitat that could cause long-term declines in desert anuran populations. PMID- 28988395 TI - Effect of roxithromycin on mucosal damage, oxidative stress and pro-inflammatory markers in experimental model of colitis. AB - OBJECTIVE AND DESIGN: Roxithromycin, a macrolide antibiotic, exhibits anti inflammatory property. The present study was designed to evaluate its protective effect in a rat model of colitis. METHODS: The anti-inflammatory property of roxithromycin was first validated in rat paw edema model at 5 and 20 mg/kg doses where it produced 19 and 51% inhibition of paw swelling induced by carrageenan. The efficacy of roxithromycin was evaluated at these doses in a rat model where colitis was induced by intra-colonic instillation of acetic acid. Rats were divided into six groups viz. normal control, experimental control and drug treated groups: roxithromycin 5 and 20 mg/kg, diclofenac 10 mg/kg and mesalazine 300 mg/kg. All drugs were given orally 1 h before induction of colitis. The macro and microscopic changes, mean ulcer score, mucus content and markers of oxidative stress and inflammation were evaluated in all the groups after 24 h. RESULTS: Pretreatment with roxithromycin markedly decreased hyperemia, ulceration, edema and restored histological architecture. The protection afforded by roxithromycin was substantiated by dose-dependent increase in mucus content, normalization of markers of oxidative stress (GSH and TBARS) and levels of TNF-alpha, PGE2 and nitrite along with marked decrease in expression of NFkappaB (p65), IL-1beta and COX-2. The protective effect of roxithromycin was found to be comparable to mesalazine while diclofenac was found ineffective. CONCLUSION: Our study demonstrates that roxithromycin ameliorates experimental colitis by maintaining redox homeostasis, preserving mucosal integrity and downregulating NFkappaB mediated pro-inflammatory signaling and suggests that it has a therapeutic potential in inflammatory conditions of the colon. PMID- 28988396 TI - Performance assessment framework for groundwater treatment plants in Arid Environments: a case of Buraydah, Saudi Arabia. AB - In arid environmental regions, such as the Kingdom of Saudi Arabia (KSA), each and every drop of groundwater needs to be efficiently utilized to meet growing water demands. Ground water treatment plants (WTPs) are regularly being monitored by the municipalities to ensure safe water supply. However, analyzing large data to assess the performance of a WTP has always been a daunting task for plant's management. Most of existing performance assessment frameworks were developed for surface WTPs. In this research, an assessment framework using performance-based water quality indices (P WQI) is developed to facilitate senior management of ground WTPs for effective decision-making. The framework is also implemented on a case study of Buraydah, Qassim, Saudi Arabia. Five most important water quality parameters (WQPs) have been selected to assess the performance of different components of the WTP, including raw water, pre-treatment, ultrafiltration, sand filtration, reverse osmosis, and final product. Depending on the relative importance of WQPs for a specific treatment process, different weighting schemes have been developed for each treatment process using fuzzy analytical hierarchical process (FAHP) to address the possible uncertainties in data and imprecision in expert opinion. Subsequently, fuzzy weighted sum method (FWSM) is employed to develop aggregated P WQI for assessing average monthly performance during the year 2016. Study results show that all the units consistently performed "high," and the plant is meeting drinking water quality standards throughout the year. Hypothetical scenario analysis revealed robustness of the developed framework by showing lacking performance in case failure of different units. PMID- 28988397 TI - Risk factors for development of severe post-traumatic elbow stiffness. AB - PURPOSE: The purpose of this study was to compare different grades of elbow stiffness and investigate demographic, injury, and treatment factors potentially associated with the development of severe elbow stiffness. METHODS: We performed a retrospective study involving 169 patients with post-traumatic elbow stiffness between June 2014 and June 2016. Patient demographics, injury, and treatment details were reviewed. Patients were classified into three groups according to the elbow motion. Ordinal regression analyses were performed to examine the independent factors. RESULTS: Patients were classified into: mild (49 patients), moderate (59 patients), and severe (61 patients) groups. Patients with severe stiffness had a significantly worse elbow functional performance. Univariate ordinal regression revealed that severe elbow stiffness was associated with high energy injury (odds ratio [OR] 4.73), olecranon fracture (OR 1.92), fracture dislocation (OR 2.28), and open fracture (OR 3.24). Multivariate regression showed that higher-energy injuries were associated with severe stiffness (OR 4.45, p = 0.003). CONCLUSIONS: Elbow stiffness after fracture surgery often results in joint stiffness. Severe stiffness often resulted in more significant functional impairment. Our study suggested that high-energy injuries were associated with the development of severe elbow stiffness. PMID- 28988398 TI - Synthetic green fluorescent protein chromophore analogues with a positive charge at the phenyl-like group. AB - Synthetic green fluorescent protein (GFP) chromophore analogues with a positive charge at the phenyl-like group have the highly electrophilic amidine carbon, smaller LUMO-HOMO energy gap, red-shifted electronic absorptions and fluorescent emissions, and accelerated E-Z thermoisomerization rates. They are water-labile and their hydrolysis results in ring-opening of the imidazolinone moiety with a half life around 25-37 h in D2O at 25 degrees C. PMID- 28988400 TI - Left ventricle assist devices and driveline's infection incidence: a single centre experience. AB - Different left ventricular assist devices (LVADs) are provided of different driveline exit sites: HeartWare HVAD presents abdominal power-cable-supply, while the Jarvik 2000 LVAD is powered by a retroauricular driveline. We analyzed 93 LVAD-implanted patients from January-2009 to October-2016 (41 HeartWare and 52 Jarvik 2000), hypothesizing a different incidence of infection, according to driveline exit site. The two populations were propensity matched for the demographic data and preoperative variables, and the outcomes were further analyzed. Nine driveline infections (DLIs) were in each LVAD group recorded (22% for HVAD and 17% for Jarvik 2000). The incidence of the complication was similar between groups (p = 0.97), even during time (p = 0.27 within 6 months and p = 0.16 over 6 months of support). Age at implant (p = 0.01), revision for bleeding (p = 0.05), days of postoperative intubation (p = 0.002), and ICU stay (p < 0.001), as well as days on device (p < 0.001) were identified as risk factors for DLIs. The type of device and the driveline exit site were not statistically co related to infections. Similar infection-freedom survival was identified (p = 0.87). Younger age at implant, revision for bleeding, prolonged mechanical ventilation, delayed rehabilitation, as well as long time LVAD support were identified as risk factors for exit site DLIs. Despite similar incidence of DLIs, the different management and care of the retroauricular exit site makes it more appropriate and comfortable in long-term support. PMID- 28988399 TI - Control of HIV infection by IFN-alpha: implications for latency and a cure. AB - Viral infections, including HIV, trigger the production of type I interferons (IFNs), which in turn, activate a signalling cascade that ultimately culminates with the expression of anti-viral proteins. Mounting evidence suggests that type I IFNs, in particular IFN-alpha, play a pivotal role in limiting acute HIV infection. Highly active anti-retroviral treatment reduces viral load and increases life expectancy in HIV positive patients; however, it fails to fully eliminate latent HIV reservoirs. To revisit HIV as a curable disease, this article reviews a body of literature that highlights type I IFNs as mediators in the control of HIV infection, with particular focus on the anti-HIV restriction factors induced and/or activated by IFN-alpha. In addition, we discuss the relevance of type I IFN treatment in the context of HIV latency reversal, novel therapeutic intervention strategies and the potential for full HIV clearance. PMID- 28988401 TI - The Trabecular Bone Score (TBS) Complements DXA and the FRAX as a Fracture Risk Assessment Tool in Routine Clinical Practice. AB - PURPOSE OF THE REVIEW: There is an increasing body of evidence that the trabecular bone score (TBS), a surrogate of bone microarchitecture extracted from spine DXA, could play an important role in the management of patients with osteoporosis or at risk of fracture. The current paper reviews this published body of scientific literature on TBS and answers the most relevant clinical questions. RECENT FINDINGS: TBS has repeatedly been proven to be predictive of fragility fractures, current and future, and this is largely independent of BMD, CRF, and the FRAX, and when used in conjunction with any one of these measures, it consistently enhances their accuracy. There also is a growing body of evidence indicating that the TBS has particular advantages over BMD for specific causes of increased fracture risk, like chronic corticosteroid excess, type-2 diabetes, and chronic kidney disease, and patients being treated with anti-aromatase and primary hyperparathyroidism, conditions wherein BMD readings are often misleading. TBS enhances performance of the FRAX tool, where its greatest utility appears to lie in its ability to accurately classify those patients whose BMD level lies close to the intervention threshold, aiding in decisions on whether treatment is warranted or not. Furthermore, TBS has also particular advantages over BMD in secondary osteoporosis. While the role of TBS with monitoring could be important as the different molecules impact logically TBS to various degrees, large clinical trials are still needed. PMID- 28988402 TI - Nutritional markers may identify patients with greater risk of re-admission after geriatric hip fractures. AB - PURPOSE: Osteoporotic hip fractures are increasing in prevalence with the growing elderly population. Morbidity and mortality remain high following osteoporotic hip fractures despite advances in medical and surgical treatments. The associated costs and medical burdens are increased with a re-admission following hip fracture treatment. This study sought to identify demographic and clinical values that may be a predictive model for 30-day re-admission risk following operative management of an isolated hip fracture. METHODS: Between January 1, 2013 and April 30, 2015 all patients admitted to a single academic medical centre for treatment of a hip fracture were reviewed. Candidate variables included standard demographics, common laboratory values, and markers of comorbid conditions and nutrition status. A 30-day, all-cause re-admission model was created utilizing multivariate logistic regression. RESULTS: A total of 607 patients with hip fractures were identified and met the inclusion criteria; of those patients, 67 were re-admitted within 30 days. Univariate analysis indicates that the re admission group had more comorbidities (p < 0.001) and lower albumin (p = 0.038) and prealbumin (p < 0.001). The final, reduced model contained 12 variables and incorporated four out of five nutritional makers with an internally, cross validated C-statistic of 0.811 (95% CI: 0.754, 0.867). CONCLUSION: Our results indicate that specific nutritional laboratory markers at the index admission may identify patients that have a greater risk of re-admission after hip fracture. This model identifies potentially modifiable risk factors and may allow orthogeriatricians to better educate patients and better treat post-operative nutritional status and care. PMID- 28988403 TI - Deterministic and stochastic analysis of an eco-epidemiological model. AB - Chronic wasting disease (CWD) is a contagious prion disease among the deer family that has the potential to disrupt the ecosystems where deer occur in abundance. To understand the dynamics of this emerging infectious disease, we consider a simple eco-epidemic model where the host population is infected by CWD. Boundedness of the system is established. The structure of equilibria and their linearized stability are investigated. The persistence condition is discussed. By constructing a suitable Lyapunov function, we discuss the global stability of the endemic equilibrium. Local bifurcation (transcritical) around the boundary equilibria is developed. Sufficient conditions for the existence of Hopf bifurcation are derived. Further, we have also introduced white type of noise into the system to investigate stochastic stability. This suggests that the deterministic model is robust with respect to stochastic perturbation. Some numerical simulations are performed to validate our results. PMID- 28988404 TI - Temporal Changes in Transcription Factor Expression Associated with the Differentiation State of Cerebellar Neural Stem/Progenitor Cells During Development. AB - During central nervous development, multi-potent neural stem/progenitor cells located in the ventricular/subventricular zones are temporally regulated to mostly produce neurons during early developmental stages and to produce glia during later developmental stages. After birth, the rodent cerebellum undergoes further dramatic development. It is also known that neural stem/progenitor cells are present in the white matter (WM) of the postnatal cerebellum until around P10, although the fate of these cells has yet to be determined. In the present study, it was revealed that primary neurospheres generated from cerebellar neural stem/progenitor cells at postnatal day 3 (P3) mainly differentiated into astrocytes and oligodendrocytes. In contrast, primary neurospheres generated from cerebellar neural stem/progenitor cells at P8 almost exclusively differentiated into astrocytes, but not oligodendrocytes. These results suggest that the differentiation potential of primary neurospheres changes depending on the timing of neural stem/progenitor cell isolation from the cerebellum. To identify the candidate transcription factors involved in regulating this temporal change, we utilized DNA microarray analysis to compare global gene-expression profiles of primary neurospheres generated from neural stem/progenitor cells isolated from either P3 or P8 cerebellum. The expression of zfp711, zfp618, barx1 and hoxb3 was higher in neurospheres generated from P3 cerebellum than from P8 by real-time quantitative PCR. Several precursor cells were found to express zfp618, barx1 or hoxb3 in the WM of the cerebellum at P3, but these transcription factors were absent from the WM of the P8 cerebellum. PMID- 28988405 TI - A case of adenocarcinoma developed in the small intestine with chronic strongyloidiasis. AB - We experienced a case of intestinal strongyloidiasis complicated by jejunal carcinoma. A Japanese male in his 50s, who has a 7-year medical history of duodenal ulcers, complained of loss of appetite, nausea, vomiting and diarrhea. Computed tomography and gastroduodenal endoscopic examination revealed a stenosis of the duodenum. To remove the stenosis, gastric bypass surgery was performed. The pathological diagnosis of the resected jejunum was strongyloidiasis and well differentiated adenocarcinoma with subserosal invasion and vascular infiltration. After administration of Ivermectin, Strongyloides stercoralis was not found in any biopsies or in the specimens of the intestine, which were resected due to cancer recurrence 2 years later. There are three possibilities for the reason of coexistence of S. stercoralis and adenocarcinoma: S. stercoralis caused the adenocarcinoma, S. stercoralis moved to the carcinoma, or just coincidence. Although it is difficult to prove a causal relationship between S. stercoralis and adenocarcinoma, this is the first report of adenocarcinoma developed in the jejunum with chronic strongyloidiasis. The number of nematode infections, including strongyloidiasis, is decreasing in Japan, although not worldwide. Therefore, it should be considered in patients with prolonged intestinal ulcers. PMID- 28988406 TI - Low level of circulating basophil counts in biopsy-proven active lupus nephritis. AB - Basophils have been shown to be important players in promoting lupus nephritis (LN). However, the relationship between circulating basophil counts and renal pathology activity of LN remains unclear. In this retrospective study, 159 clinical and pathology samples from patients with biopsy-proven LN were analyzed. The renal activity and classification were evaluated according to renal pathology. The correlations between circulating basophil counts and renal pathology activity index were assessed. Overall, circulating basophil counts correlated with total systemic lupus erythematosus disease activity index (SLEDAI) score (r = - 0.31), renal SLEDAI score (r = - 0.35), activity index (AI) score(r = - 0.40), and renal histologic activity parameters (p < 0.05, respectively). Compared with systemic lupus erythematosus (SLE) non-LN patients, the LN group had lower basophil counts (0.007 +/- 0.007 vs. 0.011 +/- 0.010 * 109/L, p = 0.04). Subgroup analyses revealed that the circulating basophil counts in group B (AI > 8) were significantly lower than that in group A (AI <= 8) (0.004 +/- 0.006 vs. 0.009 +/- 0.009 * 109/L, p < 0.001). The difference was still significant when eliminating the influence of SLEDAI. Significant differences were found in circulating basophil counts among LN pathology classification groups (p < 0.01). Groups of classes III, IV, and V were more likely to have lower circulating basophil counts when compared with group of class I/II (p < 0.05). These findings suggest a potential role of circulating basophil counts as a convenient and helpful marker for renal activity of LN. PMID- 28988408 TI - Response to the Letter to the Editor Regarding "Kinetics of Radiological Response of Thoracic Invasive Fungal Disease in Chronic Granulomatous Disease". PMID- 28988407 TI - Accountability Studies on Air Pollution and Health: the HEI Experience. AB - PURPOSE OF REVIEW: Assessing health effects of air quality interventions is of ever-increasing interest. Given the prominent role Health Effects Institute (HEI) has played in accountability research, this review focuses on HEI's recent experiences, the challenges it has encountered, and provides possible directions for future research. RECENT FINDINGS: Most accountability studies to date have focused on effects of relatively short-term, local-scale, and sometimes temporary interventions. Only a few recent accountability studies have sought to investigate large-scale, multiyear regulatory programs. Common challenges encountered include lack of statistical power, how to account appropriately for background trends in air quality and health, and difficulties in direct attribution of changes in air pollution and health to a single intervention among many regulatory actions. New methods have been developed for accountability research that has shown promise addressing some of those challenges, including use of causal inference methods. These and other approaches that would enhance the attribution of changes in air quality and health directly to an intervention should continue to be further explored. In addition, integration of social and behavioral sciences in accountability research is warranted, and climate related co-benefits and dis-benefits may be considered. PMID- 28988409 TI - The Nutritional and Health Benefits of Kiwiberry (Actinidia arguta) - a Review. AB - The kiwiberry (Actinidia arguta) is a new product on the market that is enjoying growing consumer acceptance around the world. This widespread interest has created increased demand for identification of the kiwiberry's nutritional health benefits. Containing over 20 essential nutrients and a range of vitamins, the kiwiberry comes near the top of fruits classed as superfoods. It is one of the richest sources of vitamin C with up to 430 mg/100 g fresh weight (FW) and is considered the richest dietary source of myo-inositol (up to 982 mg/100 g FW). The kiwiberry is also one of the richest sources of lutein (up to 0.93 mg/100 g FW) in commonly consumed fruit. Furthermore, containing up to 1301.1 mg/100 g FW phenolics and significant amounts of the essential minerals of potassium, calcium and zinc, the kiwiberry rates very highly as a 'healthy food'. The type and number of this fruit's medicinally promising nutrients have motivated ongoing investigations into its antioxidant, anti-tumour and anti-inflammatory properties. Early research has pointed to the kiwiberry being a very promising treatment for some cancers and health issues involving the gastrointestinal system, hypercholesterolemia and certain cancers. A pharmaceutical composition of A. arguta, A. kolomikta, and A. polygama extracts has already been registered for the prevention and treatment of some immune (inflammatory) mediated diseases, as well as the treatment of some non-allergic inflammatory diseases. This paper reviews and highlights the limited nutritional and therapeutic information currently available on the kiwiberry, a minor fruit possessing such major properties. PMID- 28988410 TI - A case of macrocystic-type serous cystic neoplasm with repeated pancreatitis within a short period of time. AB - The patient was a 39-year-old woman in whom computed tomography (CT) in 201X had revealed a pancreatic cystic neoplasm (PCN) of 4.3 cm in diameter in the pancreatic body. In June 201X + 3, the patient consulted our hospital regarding severe acute pancreatitis. The condition improved through treatment with large volume fluid replacement and continuous regional arterial infusion therapy. Thereafter, acute pancreatitis recurred twice, in November 201X + 3 and in January 201X + 4. During an 8-month period, acute pancreatitis occurred three times. The PCN was examined by endoscopic ultrasound, thin-slice contrast enhanced CT, and T2-weighted magnetic resonance imaging, which led to the diagnosis of macrocystic-type serous cystic neoplasm (SCN). The SCN was found to be 5.8 cm in diameter with dilatation of the main pancreatic duct (MPD) caudal to the SCN for 3 years. We suspected that the repeated pancreatitis had been obstructive pancreatitis resulting from displacement of the MPD caused by the SCN, and therefore recommended that the patient undergo surgery for the SCN. In March 201X + 4, distal pancreatectomy was performed. In the resected specimen, a macrocystic-type SCN was diagnosed. No recurrence of acute pancreatitis has been observed postoperatively. A macrocystic-type SCN with repeated pancreatitis within a short period of time is rare. PMID- 28988411 TI - How reliably can computed tomography predict thyroid invasion prior to laryngectomy? AB - OBJECTIVES/HYPOTHESIS: There is little evidence to support the removal of thyroid tissue during total laryngectomy. Although oncological control of the tumor is the priority, thyroidectomy can lead to hypothyroidism and hypoparathyroidism. This study aimed to test the usefulness of preoperative computed tomography in predicting histological invasion of the thyroid. STUDY DESIGN: Ambispective cohort study. METHODS: All patients undergoing total laryngectomy for squamous cell carcinoma at one center from 2006 to 2016 were included. Data were recorded prospectively as part of the patients' standard care, but were collated retrospectively, giving this study an ambispective design. The histology report for thyroid invasion was taken as the gold standard. The computed tomography report was categorized by invasion of tumor into intralaryngeal, laryngeal cartilage involvement, and extralaryngeal tissues. RESULTS: Seventy-nine patients were included. Nine patients had thyroid involvement on histology, translating to an incidence of 11.29% in this population. The positive predictive value for cartilage involvement on computed tomography for thyroid invasion was 52.9% (95% confidence interval [CI]: 28.5%-76.1%) and the negative predictive value was 100% (95% CI: 92.7%-100%).The positive predictive value for extralaryngeal spread on computed tomography for thyroid involvement was 100% (95% CI: 62.9%-100%), and the negative predictive value was also 100% (95% CI: 93.5%-100%). CONCLUSIONS: This study has shown that preoperative computed tomography is an effective method of ruling out thyroid gland invasion. The absence of extralaryngeal spread on computed tomography has been shown to be the most useful finding, with a high negative predictive value and a narrow 95% CI. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:1099-1102, 2018. PMID- 28988412 TI - Cognitive outcomes among Latino survivors of childhood acute lymphoblastic leukemia and lymphoma: A cross-sectional cohort study using culturally competent, performance-based assessment. AB - BACKGROUND: This study sought to characterize cognitive outcomes among Latino survivors of childhood acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LL). PROCEDURE: In this cross-sectional cohort study, Latino survivors of ALL (n = 57) and LL (n = 5) aged 6-16 years were pooled and evaluated using validated measures of cognitive, academic, and behavioral function and English language proficiency. Performance was compared with norms using single-sample t tests. RESULTS: In this cohort (n = 62, 50% male), mean ages at diagnosis and testing were 4.5 and 10.8 years, respectively; mean time off treatment was 44.7 months. All participants spoke English and over half (57%) identified Spanish as the primary language in the home. Forty-two families (68%) placed in the two lowest Hollingshead socioeconomic status categories. Participants were below average for working memory (P < 0.001). Overall, participants were in the average range, but significantly lower than published norms on domain-specific measures of verbal comprehension (P < 0.001); perceptual reasoning (P = 0.033); processing speed (P = 0.003); visual memory (P < 0.001); visuomotor attention, scanning, and sequencing (P = 0.005); and reading comprehension (P = 0.001). Parents reported concerns with working memory (P < 0.001) and metacognition (P = 0.014). CONCLUSIONS: Similar to other childhood ALL/LL survivors, overall cognitive function in this Latino sample was relatively preserved but selected deficits were observed. Routine cognitive screening is indicated in this population. PMID- 28988413 TI - Oral health of children and adolescents with mucopolysaccharidosis and mother's Sense of Coherence. AB - AIMS: The purpose of this study is assess the association between mother's Sense of Coherence (SOC) and the oral health status of children with and without mucopolysaccharidosis (MPS). METHODS: A cross-sectional study was carried out with 29 children/adolescents with MPS and 29 children/adolescents without MPS, and their mothers in Brazil. Mothers completed the Antonovsky's SOC instrument (SOC-13) and their children's oral cavity had been examined for developmental defects of enamel (DDE), occlusal problems, dental caries (DMFT/dmft) and oral hygiene. This study was approved by the Research Ethics Committee of the Universidade Federal de Minas Gerais. RESULTS: Mothers of children with MPS had lower SOC scores (mean: 33.3 [+/-4.0]) compared with mothers of children without MPS (mean: 36.9 [+/-4.5]) (p < 0.001). Mother's SOC of children with MPS were lower for those children with one or more decayed teeth (31.5 [+/-3.2]) than for those children/adolescents without caries (35.7 [+/-3.8]) (p = 0.004) and lower for those children/adolescents with one or more missing teeth (30.2 [+/-0.9]) than for those individuals identified without missing teeth (33.8 [+/-4.1]) (p = 0.046). CONCLUSION: Mothers' SOC of children/adolescents with MPS was associated with dental caries experience in their children. Improving mothers' SOC should contribute to a better quality of life for their children. PMID- 28988414 TI - Upper esophageal sphincter augmentation reduces pharyngeal reflux in nasogastric tube-fed patients. AB - OBJECTIVES/HYPOTHESIS: Aspiration of gastric refluxate is one of the most commonly observed complications among long-term nasogastric tube (NGT) fed patients. The upper esophageal sphincter (UES) pressure barrier is the main defense mechanism against pharyngeal reflux of gastric contents. Our objective was to investigate the efficacy and safety of the UES assist device (UES-AD) in preventing gastric reflux through the UES in long-term NGT-fed patients. STUDY DESIGN: Self-Controlled Case series. METHODS: We studied 10 patients (mean age = 90.6 +/- 3.4 years, four females) with dysphagia caused by stroke or dementia who were fed for 0.5 to 5 years (median = 3 years) by NGT. External pressures of 20 to 30 mm Hg were applied by using a handmade UES-AD, which was started 2 hours after the beginning of NGT infusion and was alternated between periods of 2 hours on and 2 hours off, for a total of 12 hours. Placement of the impedance sensors within the UES was guided by high-resolution manometry. Trans-UES and intraesophageal reflux events were recorded by using 24-hour combined pH impedance measurements. RESULTS: No aspiration pneumonia events were noted in the period 1 month before or during the study in any of the cohort. Baseline UES pressure averaged 17.5 +/- 9.4 mm Hg and was increased to 38.9 +/- 11.9mm Hg after application of the UES-AD. Overall frequency of trans-UES reflux decreased significantly with the UES-AD compared to without (0.8 +/- 0.9 vs. 3.3 +/- 2.8, P < .05 for the 12-hour study period). There was no effect of the UES-AD on esophageal reflux events (7.4 +/- 4.4 vs. 6.4 +/- 3.0, P > .05). CONCLUSIONS: UES AD significantly decreases the number of trans-UES reflux events and can potentially reduce the aspiration risk associated with NGT feeding. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:1310-1315, 2018. PMID- 28988415 TI - Safety of outpatient thyroidectomy: Review of the American College of Surgeons National Surgical Quality Improvement Program. AB - OBJECTIVES/HYPOTHESIS: To investigate national trends in admission status after thyroidectomy in the United States and to evaluate the factors associated with 30 day unplanned readmission and reoperation. STUDY DESIGN: Retrospective review of American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) METHODS: The ACS-NSQIP database was queried for patients who underwent a partial or total thyroidectomy between 2005 and 2014. Outpatient surgery was defined as discharge on the day of surgery. Patient demographic information, unplanned hospital readmission, and reoperation were reviewed. Risk factors were identified using logistic regression modeling. RESULTS: A total of 76,604 cases met inclusion criteria as described above. There were 1,473 (1.9%) patients who underwent reoperation and 477 unplanned 30-day readmissions (1.4%) for procedures performed since 2012. There was a significant positive trend in the percentage of thyroidectomy (partial and total) patients who underwent outpatient procedures by year of operation (P < .001). Outpatient procedures were not more likely to have unplanned readmissions or reoperations. Independent patient risk factors for unplanned readmission and reoperation included current dialysis, chronic steroid use, unintentional weight loss, American Society of Anesthesiologists class 3 to 4, and active bleeding disorders. CONCLUSIONS: Over the past decade there has been a clear trend toward increasing outpatient thyroid surgery. Thyroidectomy performed as an outpatient was not found to be an independent risk factor for readmission or reoperation. Patients with serious medical comorbidities and active bleeding disorders are at increased risk of unplanned readmission or reoperation and should have their surgery performed on an inpatient basis. LEVEL OF EVIDENCE: 2c. Laryngoscope, 128:1249-1254, 2018. PMID- 28988416 TI - Comment on: Value of flow cytometric analysis of peripheral blood samples in children diagnosed with acute lymphoblastic leukemia. PMID- 28988417 TI - Self-apposing stent-assisted coil embolization for the treatment of coronary artery aneurysm. AB - Coronary artery aneurysms (CAA) represent an uncommon disease with yet unclear standards of treatment. Clinical and anatomic characteristics determine choice of treatment. Stent-assisted coil embolization has been described as a valuable option for management of patients with wide-neck coronary aneurysms. Choice of appropriate stent sizing can be challenging particularly when there is a large difference between proximal and distal diameters. We report a case of stent assisted coil embolization of a coronary aneurysm using a self-expandable stent. This type of stent can be helpful to treat CAA involving coronary sites where marked tapering of vessel diameter is often present. PMID- 28988418 TI - Clinical utility of 18 F-fluorodeoxyglucose/positron emission tomography in diagnosis of immunoglobulin G4-related sclerosing sialadenitis. AB - OBJECTIVES/HYPOTHESIS: The aim of this study was to evaluate the utility of 18 F fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for accurately diagnosing immunoglobulin G4-related sclerosing sialadenitis (IgG4-SS). STUDY DESIGN: Retrospective cohort study. METHODS: We reviewed the records of 64 patients with IgG4-SS (35 male and 29 female patients) and 10 patients with clinically suspected IgG4-SS. Pathological diagnoses of patients clinically suspected with IgG4-SS included four cases of malignant lymphoma, one case of multicentric Castleman disease, one case of Sjogren's syndrome, and four cases of sialadenitis. All patients underwent submandibular gland (SMG) biopsies and baseline FDG-PET/CT evaluation. Clinical, serological, pathological, and PET/CT findings were analyzed. We also investigated maximum standardized uptake values (SUVmax) in the salivary glands of 15 patients with malignant disease of the salivary glands during the same period. RESULTS: Increased FDG uptake in the SMG and parotid gland was found in 63 (98%) and 23 (35%) patients with IgG4-SS, respectively. FDG uptake of the bilateral SMG and unilateral SMG was recorded in 57 patients (89%) and six patients (9%), respectively. Mean SUVmax in patients with malignant disease of the salivary glands was significantly higher than that in patients with IgG4-SS (P = .035). We defined a positive test for IgG4-SS diagnosis as high SMG FDG uptake and serum IgG4 level >=135 mg/dL, resulting in a sensitivity, specificity, and accuracy of 96.9%, 90.0%, and 86.4%, respectively. CONCLUSIONS: FDG-PET/CT findings in combination with serological and clinical findings may have the capacity to diagnose IgG4-SS and lead to less-invasive biopsy procedures. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:1120-1125, 2018. PMID- 28988419 TI - Poly(norepinephrine)-coated open tubular column for the separation of proteins and recombination human erythropoietin by capillary electrochromatography. AB - Recombinant human erythropoietin is an important therapeutic protein with high economic interest due to the benefits provided by its clinical use for the treatment of anemias associated with chronic renal failure and chemotherapy. In this work, a poly(norepinephrine)-coated open tubular column was successfully prepared based on the self-polymerization of norepinephrine under mild alkaline condition, the favorable film forming and easy adhesive properties of poly(norepinephrine). The poly(norepinephrine) coating was characterized by scanning electron microscopy and measurement of the electro-osmotic flow. The thickness of the coating was about 431 nm. The electrochromatographic performance of the poly(norepinephrine)-coated open tubular column was evaluated by separation of proteins. Some basic and acidic proteins including two variants of bovine serum albumin and two variants of beta-lactoglobulin achieved separation in the poly(norepinephrine)-coated open tubular column. More importantly, the column demonstrated separation ability for the glycoforms of recombinant human erythropoietin. In addition, the column demonstrated good repeatability with the run-to-run, day-to-day, and column-to-column relative standard deviations of migration times of proteins less than 3.40%. PMID- 28988420 TI - The effect of vocal fold augmentation on cough symptoms in the presence of glottic insufficiency. AB - OBJECTIVE: To determine the effect of injection augmentation of the vocal folds on chronic cough symptoms in patients with glottic insufficiency. METHODS: Medical records from 146 consecutive patients who underwent vocal fold injection augmentation by a fellowship-trained laryngologist between 2013 and 2015 were reviewed. Twenty-three patients (12 male) met inclusion criteria of a vocal fold augmentation injection, cough symptoms lasting more than 8 weeks, and glottic insufficiency as determined by shortened closed phase on stroboscopy. Exclusion criteria included lack of cough complaints, diagnosis of vocal fold immobility, previous history of vocal fold augmentation, and incomplete data sets. Data collected included age, gender, pre- and 1-month postinjection Cough Severity Index (CSI) scores, location of injection (unilateral or bilateral), and patient statement of percent change in symptoms that was recorded at 1-month postinjection visit. RESULTS: Paired t test indicated a significant decrease in CSI scores from pre- (m = 18.5) to 1-month postinjection (m = 12.1) (P = 0.004). Eighteen patients (78.2%) reported a 50% or greater improvement in cough symptoms at the 1-month postinjection visit. CONCLUSION: Injection augmentation of the vocal folds in the presence of glottic insufficiency appears to improve cough symptoms, as was reported by CSI in patients who are refractory to other medical and behavioral treatments. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:1316-1319, 2018. PMID- 28988421 TI - Survival of renal cell carcinoma metastatic to nonthyroid head and neck region: A systematic review. AB - OBJECTIVE: Metastasis of renal cell carcinoma to nonthyroid head and neck region is rare. Survival benefit for complete metastasectomy of more common renal cell foci has been reported in the literature. It is uncertain whether metastasectomy in nonthyroid head and neck region would provide a similar benefit. DATA SOURCES: We conducted a retrospective review of all renal cell metastases to the head and neck region treated in the past 15 years at an academic hospital, and a systematic review of all relevant reports with survival data in the literature between 1960 and 2016. REVIEW METHODS: An analysis of pooled data was performed to estimate overall survival. RESULTS: Six cases from our institution and 260 independent cases reported in the literature were included in the survival analyses (n = 266). The median follow-up time was 12 months (range 0-180 months). The overall median survival was 36 months (95% confidence interval [CI] 23.7 48.3). The median survival for those who underwent complete metastasectomy in the head and neck was significantly higher at 60 months (95% CI 41.1-78.9) than those who had incomplete or no metastasectomy (12 months, 95% CI 9.5-14.5). Multivariable Cox proportional hazards model estimated that, after controlling for potential confounders, complete metastasectomy remained associated with reduced risk of death (hazard ratio 0.44, 95% CI 0.29-0.69). CONCLUSION: Complete metastasectomy was associated with 4-year longer median overall survival than incomplete metastasectomy or no metastasectomy. Laryngoscope, 128:889-895, 2018. PMID- 28988422 TI - Comparison of two cytoreductive regimens for alphabeta-T-cell-depleted haploidentical HSCT in pediatric malignancies: Improved engraftment and outcome with TBI-based regimen. AB - BACKGROUND: Graft manipulation using selective depletion of alphabeta-T cells provides a source of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) enriched in effector cells. We report our experience implementing this haplo-HSCT for high-risk malignancies in pediatric patients focusing on the conditioning regimen. PROCEDURE: We performed a retrospective study of patients who underwent T-cell receptor alphabeta-depleted haplo-HSCT for high-risk pediatric malignancies. RESULTS: Eighteen patients underwent haplo-HSCT using this method. The initial reduced-toxicity chemotherapy-based conditioning regimen was given to eight patients, and resulted in a high rate of graft rejections (six of eight patients). Thus, total body irradiation (TBI) based regimen was introduced in the following 10 patients and resulted in engraftment in all patients. Neutrophil and platelet engraftment were rapid (median time to engraft, 10 days and 12 days, respectively). Significant treatment-related complications for both cohorts were all due to graft failure in patients receiving chemotherapy based conditioning, with a treatment-related mortality rate of 17%. None of the patients developed hepatic sinusoidal-obstruction syndrome, and no grade III-IV acute graft versus host disease (GVHD) was observed. The majority of patients were free of immunosuppression in the first 100 days post-HSCT, and only two patients developed chronic GVHD. The cumulative incidence of relapse was 39%. Compared to patients conditioned with chemotherapy, patients conditioned with TBI had superior actuarial overall survival (66% vs. 37%, P = 0.05) and event-free survival (61% vs. 33%, P = 0.04). CONCLUSIONS: A TBI-based conditioning for haplo HSCT using alphabeta-T-cell depletion for malignant diseases ensured engraftment and resulted in acceptable outcomes. PMID- 28988423 TI - Positive fresh frozen section margins as an adverse independent prognostic factor for local recurrence in oral cancer patients. AB - OBJECTIVES: To access 1) the value of further surgical resection (completion surgery) in cases with a positive intraoperative margin analysis, and 2) whether cancers that undergo completion surgery following positive intraoperative margin analysis with subsequent negative margins should be considered true margin negative (R0) resections in terms of adjuvant treatment planning. STUDY DESIGN: Retrospective analysis of patients with primary oral cancer. METHODS: One hundred and fifty-one patients underwent primary surgical resection of oral squamous cell carcinoma with intraoperative margin examination. In all cases for which frozen section margin analysis was positive, an extended resection was performed. Only patients with clear final margins were included in the study. RESULTS: The intraoperative analysis of surgical margins revealed that cancer-free margins were achieved in 123 cases (81.5%). In 28 specimens (18.5%), the surgical margins were positive. Local recurrence was observed in 28 (18.5%) patients, whereas regional recurrence developed in 30 (19.9%) patients. Factors significantly (P < 0.05) increased the risk of local recurrence: advanced stage of the disease (III/IV), node N-positive status, lymphovascular invasion and positive fresh frozen surgical margins. On multivariate analysis, only positive fresh frozen surgical margins remained significant independent adverse factors. CONCLUSION: Our study demonstrates that positive fresh frozen margins, regardless of re resection to R0 status, could be a powerful adverse factor that determines an aggressive nature of the tumor. This feature should be taken into consideration in adjuvant treatment planning. The greatest impact this could have is in borderline clinical situations for which the indication for adjuvant treatment may be questionable. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:1093-1098, 2018. PMID- 28988424 TI - Maintenance of valvular integrity with Impella left heart support: Results from the multicenter PROTECT II randomized study. AB - BACKGROUND: The Impella 2.5 axial flow pump, which is positioned across the aortic valve, is widely employed for hemodynamic support. The present study compared structural and functional integrity of the left heart valves in patients undergoing Impella vs intra-aortic balloon pump in the randomized PROTECT II trial. METHODS AND RESULTS: Transthoracic echocardiograms were performed at baseline, 1 and 3 months in 445 patients in the PROTECT II trial. Serial studies were analyzed by an independent echocardiography core laboratory for aortic and mitral valve structure and function, and left ventricular ejection fraction (LVEF). During Impella support there was no appreciable change in the degree of baseline valvular regurgitation. There were no cases of structural derangement of the mitral or aortic valve after use of the Impella device. At 90-day follow-up, there was an average 22% relative increase in LVEF from baseline (27% +/- 9 vs. 33% +/- 11, P < 0.001). CONCLUSIONS: The present echocardiographic analysis of the PROTECT II study confirms prior observations regarding the safety of the Impella 2.5 device with respect to mitral and aortic valve function. PMID- 28988425 TI - The safety and effectiveness of adenosine diphosphate receptor inhibitor pretreatment among acute myocardial infarction patients treated with percutaneous coronary intervention in community practice: Insights from the TRANSLATE-ACS study. AB - OBJECTIVES: To understand the optimal timing of adenosine diphosphate (ADP) receptor inhibitor pretreatment prior to percutaneous coronary intervention (PCI) among acute myocardial infarction (MI) patients. BACKGROUND: The role of ADP receptor inhibitor pretreatment in this population is unclear. METHODS: A total of 9,251 ADP receptor inhibitor-naive MI patients undergoing PCI at 229 TRANSLATE ACS sites were evaluated. Adjusted risks of in-hospital major adverse cardiovascular events (MACE) and major bleeding were compared among patients with and without pretreatment using inverse probability-weighted propensity adjustment. RESULTS: Of 9,251 patients treated with either prasugrel or clopidogrel during the index MI hospitalization, 4,056 (44%) received pretreatment (ST-segment elevation MI [STEMI] 54.9%, non-STEMI 45.1%); pretreatment was used more commonly among those receiving clopidogrel than prasugrel (52% vs. 20%, P < 0.0001). MACE risks were not significantly different between patients with and without pretreatment (clopidogrel 2.1% vs. 2.2%, adjusted hazard ratio [HR] 1.00, 95% confidence interval [CI] 0.70-1.43; prasugrel 2.1% vs. 2.3%, adjusted odds ratio [OR] 0.82, 95% CI 0.42-1.60). No differences in major bleeding were observed among those receiving versus not receiving pretreatment (clopidogrel 3.1% vs. 3.5%, adjusted HR 0.94, 95% CI 0.65 1.36; prasugrel 2.5% vs. 2.7%, adjusted OR 0.93, 95% CI 0.42-2.02); results were similar when stratified by MI type. CONCLUSIONS: ADP receptor inhibitor pretreatment (44%) is commonly used among acute MI patients undergoing PCI in contemporary practice, but no significant differences were found in in-hospital MACE and/or bleeding risks between patients receiving versus not receiving pretreatment, regardless of ADP receptor inhibitor type. PMID- 28988426 TI - Primary surgery versus primary radiation-based treatment for locally advanced oropharyngeal cancer. AB - OBJECTIVE: Randomized data comparing surgery to radiation for locally advanced oropharyngeal cancer (OPC) are lacking. This study evaluated practice patterns and overall survival outcomes from the National Cancer Database. METHODS: A total of 22,676 patients with stage III to IV, locally advanced OPC were treated between 2004 to 2013 with primary chemoradiation (CRT) or surgery with adjuvant radiotherapy with or without chemotherapy (aRT +/- CT). Survival rates were estimated using the Kaplan-Meier method. Crude and adjusted hazard ratios (HR) were computed using Cox regression modeling. RESULTS: Median follow-up was 40.7 months; 8,555 and 14,121 patients received surgery with aRT +/- CT and CRT, respectively. Corresponding 3-year survival was 85.4% and 72.6% (P < 0.0001). On multivariate analysis, adjusting for age, gender, race insurance status, median income, percentage with no high-school degree, Charlson-Deyo score, clinical tumor and node stage, tumor grade, facility type, treatment at > 1 facility, and human papillomavirus (HPV) status, surgery with aRT +/- CT had a reduced hazard of death, HR, 0.79 (95% confidence interval 0.69-0.91), P = 0.001. CONCLUSION: Primary surgery with aRT +/- CT for locally advanced OPC has an improved survival compared to primary radiation-based treatment even when stratified by HPV status. LEVEL OF EVIDENCE: 2c. Laryngoscope, 128:1353-1364, 2018. PMID- 28988427 TI - Hydroxyurea therapy in UK children with sickle cell anaemia: A single-centre experience. AB - INTRODUCTION: Despite the demonstrated efficacy of hydroxyurea therapy, children with sickle cell anaemia in the UK are preferentially managed with supportive care or transfusion. Hydroxyurea is reserved for children with severe disease phenotype. This is in contrast to North America and other countries where hydroxyurea is widely used for children of all clinical phenotypes. The conservative UK practice may in part be due to concerns about toxicity, in particular marrow suppression with high doses, and growth in children. METHODS AND RESULTS: We monitored 37 paediatric patients with sickle cell anaemia who were treated with hydroxyurea at a single UK treatment centre. Therapy was well tolerated and mild transient cytopenias were the only toxicity observed. Comparative analysis of patients receiving >=26 mg/kg/day versus <26 mg/kg/day demonstrates increasing dose has a significant positive effect on foetal haemoglobin (Hb; 29.2% vs. 20.4%, P = 0.0151), mean cell volume (94.4 vs. 86.5, P = 0.0183) and reticulocyte count (99.66 * 109 /l vs. 164.3 * 109 /l, P = 0.0059). Marrow suppression was not a clinical problem with high-dose treatment, Hb 92.25 g/l versus 91.81 g/l (ns), neutrophil count 3.3 * 109 /l versus 4.8 * 109 /l (ns) and platelet count 232.4 * 109 /l versus 302.2 * 109 /l (ns). Normal growth rates were maintained in all children. Good adherence to therapy was a significant factor in reducing hospitalisations. CONCLUSION: This study demonstrates the effectiveness and safety in practice of high-dose hydroxyurea as a disease modifying therapy, which we advocate for all children with sickle cell anaemia. PMID- 28988428 TI - Risk factors for salvage surgery failure in oral cavity squamous cell carcinoma. AB - OBJECTIVES/HYPOTHESIS: Locoregional recurrences of oral cavity squamous cell carcinoma (SCC) may be diagnosed during follow-up of surgically treated patients. Nevertheless, few studies have investigated factors that impact salvage surgery failure and the mortality rates of these patients. The objectives were to identify predictive factors of salvage surgery failure and mortality in patients who undergo surgical treatment for recurrent oral cavity SCC and to compare the overall survival rates of these patients with those of patients who undergo only one surgical treatment. STUDY DESIGN: Retrospective cohort study. METHODS: Forty six patients submitted to salvage surgery for local or locoregional recurrence. RESULTS: The presence of lymph node metastasis and positive surgical margins at the salvage surgery time were the only independent factors associated with both recurrence rates (hazard ratio [HR]: 5.04 and 2.82, respectively) and mortality (HR: 3.51 and 3.24, respectively). When the overall survival rates of the 199 patients who only underwent one surgical treatment were compared to those of the 46 patients subjected to salvage surgery, a similarity was evident when patients who underwent salvage surgery did not have a new disease recurrence (70.7% vs. 54.7%, respectively; P = .158). Likewise, patients with new recurrences after salvage surgery and patients who received palliative treatment for relapsed disease had similar overall survival rates (0.6% vs. 0.0%, respectively; P = .475). CONCLUSIONS: The presence of lymph node metastasis at the time of recurrence and positive surgical margins after the salvage surgery were associated with a worse overall survival rate in patients with oral cavity SCC relapse. LEVEL OF EVIDENCE: 2b. Laryngoscope, 128:1113-1119, 2018. PMID- 28988429 TI - Homozygous indel mutation in CDH11 as the probable cause of Elsahy-Waters syndrome. AB - Two sisters from a consanguineous couple were seen in genetics department for facial dysmorphic features and glaucoma. They both had broad foreheads, hypertelorism, megalocorneas, thick eyebrows with synophrys, flat malar regions, broad and bulbous noses, and mild prognathism. Both had glaucoma, younger one also had cataracts and phthisis bulbi. Other findings included bilateral partial cutaneous syndactyly of 2nd and 3rd fingers, history of impacted teeth with dentigerous cyst in the elder one, and intellectual disability (mild and borderline). The sisters were considered to have Elsahy-Waters syndrome. In order to elucidate the underlying molecular cause, sisters and their healthy parents were genotyped by SNP arrays, followed by homozygosity mapping. Homozygous regions were further analyzed by exome sequencing in one affected individual. A homozygous indel variant segregating with the condition was detected in CDH11 (c.1116_1117delinsGATCATCAG, p.(Ile372MetfsTer9)), which was then validated by using Sanger sequencing. CDH11 encodes cadherin 11 (osteo-cadherin) that regulates cell-cell adhesion, cell polarization and migration, as well as osteogenic differentiation. Further experiments revealed that CDH11 expression was decreased in patient-derived fibroblasts as compared to the heterozygous parent and another healthy donor. Immunostaining showed absence of the protein expression in patient fibroblasts. In addition, cell proliferation rate was slow and osteogenic differentiation potential was delayed. We consider that this study reveals loss-of-function mutations in CDH11 as a probable cause of this phenotype. Next generation sequencing in further patients would both prove this gene as causative, and finely delineate this clinical spectrum further contributing in identification of other possibly involved gene(s). PMID- 28988430 TI - Recent advances in methods for the analysis of protein o-glycosylation at proteome level. AB - O-Glycosylation, which refers to the glycosylation of the hydroxyl group of side chains of Serine/Threonine/Tyrosine residues, is one of the most common post translational modifications. Compared with N-linked glycosylation, O glycosylation is less explored because of its complex structure and relatively low abundance. Recently, O-glycosylation has drawn more and more attention for its various functions in many sophisticated biological processes. To obtain a deep understanding of O-glycosylation, many efforts have been devoted to develop effective strategies to analyze the two most abundant types of O-glycosylation, i.e. O-N-acetylgalactosamine and O-N-acetylglucosamine glycosylation. In this review, we summarize the proteomics workflows to analyze these two types of O glycosylation. For the large-scale analysis of mucin-type glycosylation, the glycan simplification strategies including the ''SimpleCell'' technology were introduced. A variety of enrichment methods including lectin affinity chromatography, hydrophilic interaction chromatography, hydrazide chemistry, and chemoenzymatic method were introduced for the proteomics analysis of O-N acetylgalactosamine and O-N-acetylglucosamine glycosylation. PMID- 28988431 TI - Hearing loss on social media: Who is winning hearts and minds? AB - OBJECTIVES/HYPOTHESIS: To analyze specific patterns of Twitter usage using common references to hearing loss, and characterize the virtual public that comprises the hearing loss community to inform hearing loss stakeholders for opportunities for engagement and outreach. STUDY DESIGN: Social media network analysis. METHODS: Twitter tweets were sampled from July 2016 to September 2016 using #hearing, #hearingloss, #deaf, #hearingimpairment, #hardofhearing, #deafness, #hearingmatters, #hearinghealth, and #hearingimpaired tags. User and Twitter social community metrics were examined including temporal trends, tweet content, user activity, tweet reach, and an analysis of the tweets' social network. RESULTS: We identified and analyzed 49,208 tweets from July 2016 to September 2016 with tags relevant to hearing loss. Of the 100 most active Twitter accounts, organizations owned 67% compared to 33% owned by individuals. Commercial/for profit and informational organizations were the most common organization account owners (26% and 16%, respectively). Five unique tweets were identified as each having a reach of over 100,000 Twitter users, with the greatest reach exceeding 250,000 users. Temporal analysis identified marked retweet outliers (>300 retweets per hour) that corresponded with a widely publicized event involving the dismissal of a deaf employee from a fast-food chain store. CONCLUSIONS: Twitter accounts owned by organizations outnumbered individual accounts, and commercial/for profit user accounts were the most frequently active organization account type. Tweets pertaining to hearing loss may have a broad reach to a large community base. Analyses of social media use can be helpful in discovering issues of interest to the hearing loss community, as well as determining which users and organizations are dominating social network conversations. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:1453-1461, 2018. PMID- 28988433 TI - Does a single dose of pregabalin help with postoperative pain after septoplasty? PMID- 28988432 TI - Impact of flow, gradient, and left ventricular function on outcomes after transcatheter aortic valve replacement. AB - OBJECTIVES: To assess the impact of low flow with and without preserved left ventricular ejection fraction (LVEF) on outcomes after transcatheter aortic valve replacement (TAVR). BACKGROUND: Prior studies have shown that patients with low flow, AVG, and LVEF have worse outcomes after TAVR. It is unclear whether low AVG and LVEF remain prognostic after adjusting for flow, and how the outcomes of patients with low flow with and without preserved LVEF compare after TAVR. The goal of this study was to provide insight into these open questions. METHODS: Data from 340 TAVR patients at Brigham and Women's Hospital from 2011 through 2015 were analyzed. Low flow was defined as stroke volume index (SVI) <=35 mL/m2 , low AVG as mean gradient < 40 mmHg, and reduced LVEF as < 50%. RESULTS: Low flow was present in 96 (28.2%) patients, 48 (50.0%) of whom also had reduced LVEF. At 1 year, low flow was associated with increased mortality (21.9 vs 7.4%; P = 0.0002) and heart failure (HF) (20.8 vs 5.3%; P = 0.0113). Among patients with low flow, those with preserved LVEF had increased mortality (HR 5.17, 95% CI 2.73-9.80; P < 0.001) and HF (HR 7.69, 95% CI 3.86-15.31; P < 0.001). After adjusting for clinical factors, patients with low flow had increased mortality (HR 6.51, 95% CI 2.98-14.22; P < 0.001) and HF (HR 5.52, 95% CI 2.34-12.98; P < 0.001), while neither low AVG nor low LVEF were associated with increases in mortality or HF. CONCLUSIONS: In patients undergoing TAVR, low flow was an independent predictor of 1-year mortality and HF, and a stronger predictor than either low AVG or LVEF. Patients with low flow and preserved EF had increased mortality and HF at 1-year, while those with low flow and reduced EF had outcomes similar to patients with normal flow. PMID- 28988434 TI - Maternal and obstetrical outcome in 35 cases of well-differentiated thyroid carcinoma during pregnancy. AB - OBJECTIVES/HYPOTHESIS: Thyroid cancer, with 6% to 10% of cancer diagnoses, is one of the most common malignancies during pregnancy. Its treatment poses a risk for the pregnancy, as the thyroid gland plays a crucial role in the evolution of pregnancy. The aim of this study is to evaluate treatment of primary well differentiated thyroid carcinoma during pregnancy and fetal and maternal outcomes. STUDY DESIGN: This is an international cohort study. METHODS: Primary thyroid cancer patients were identified from the database of the International Network on Cancer, Infertility, and Pregnancy registration study. Data on histopathological characteristics, diagnostic and therapeutic interventions, outcome (obstetrical, neonatal, and maternal) and maternal follow-up were analyzed. RESULTS: Thirty-five patients with well-differentiated thyroid carcinoma were eligible. All 35 patients underwent surgery, 29 (83%) of which during pregnancy. Procedures during pregnancy were mainly total thyroidectomies (n = 24). The median number of days between diagnosis and surgical treatment was different between the groups with surgery during and after pregnancy (27 vs. 139 days, P < .001). Both maternal and neonatal outcomes were uncomplicated, regardless of gestational age during surgery. CONCLUSIONS: Well-differentiated thyroid carcinoma diagnosed during pregnancy has a favorable outcome for both mother and child. Surgical management during pregnancy has no negative impact on the pregnancy regardless of the trimester at the time of surgery. However, the potential negative effects of thyroid surgery early in pregnancy demand management of these patients in an experienced multidisciplinary team to provide the best possible care for these patients and their unborn babies. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:1493-1500, 2018. PMID- 28988435 TI - Triple therapy of vincristine, bleomycin and etoposide for children with Kaposi sarcoma: Results of a study in Malawian children. AB - BACKGROUND: Kaposi sarcoma (KS) is the most common paediatric cancer in human immunodeficiency virus (HIV) endemic countries of sub-Saharan Africa, but there is little research on management and outcomes. METHODS: Children with KS at Queen Elizabeth Central Hospital, Blantyre, Malawi treated between August 2012 and March 2015 with six courses of vincristine, bleomycin and etoposide combination chemotherapy, including antiretroviral therapy (ART) if HIV infected, were studied and outcomes compared with previously reported results. FINDINGS: Fifty six children were included; 38 (68%) were male; and 48 (86%) were HIV positive, of whom 36 (77%) were on ART at diagnosis. Median age at diagnosis was 8 years (interquartile range [IQR] 3-12) and median follow-up was 16.9 months (IQR 3.4 36.4). Quality of life improved in 45 (80%) children; the median Lansky Score increased from 80% pre-treatment to 100% post-treatment. Eighteen (32%) children had complete response to treatment. At 12 months, overall survival was 71% (95% confidence interval [CI] 56-82) and event-free survival (event = death, loss to follow-up or relapse) was 50% (95% CI 36-63). At 1 year, the risk of loss to follow-up was 13.4%. In a previous, same-site, randomized controlled study of vincristine monotherapy, vincristine and bleomycin, or oral etoposide, oral etoposide monotherapy had the best outcome with survival at 12 month of 66% (95% CI 46-80) and event-free survival of 52% (95% CI 33-68); however, loss to follow up was not reported. CONCLUSION: Overall survival, event-free survival and quality of life appear to have improved with this three-agent combination chemotherapy; however larger, randomized studies are needed to determine optimal management. PMID- 28988436 TI - One-pot synthesis of magnetic zeolitic imidazolate framework/grapheme oxide composites for the extraction of neonicotinoid insecticides from environmental water samples. AB - Magnetic zeolitic imidazolate framework 67/graphene oxide composites were synthesized by one-pot method at room temperature for the first time. Electrostatic interactions between positively charged metal ions and both negatively charged graphene oxide and Fe3 O4 nanoparticles were expected to chemically stabilize magnetic composites to generate homogeneous magnetic products. The additional amount of graphene oxide and stirring time of graphene oxide, Co2+ , and Fe3 O4 solution were investigated. The zeolitic imidazolate framework 67 and Fe3 O4 nanoparticles were uniformly attached on the surface of graphene oxide. The composites were applied to magnetic solid-phase extraction of five neonicotinoid insecticides in environmental water samples. The main experimental parameters such as amount of added magnetic composites, extraction pH, ionic strength, and desorption solvent were optimized to increase the capacity of adsorbing neonicotinoid insecticides. The results show limits of detection at signal-to-noise ratio of 3 were 0.06-1.0 ng/mL under optimal conditions. All analytes exhibited good linearity with correlation coefficients of higher than 0.9915. The relative standard deviations for five neonicotinoid insecticides in environmental samples ranged from 1.8 to 16.5%, and good recoveries from 83.5 to 117.0% were obtained, indicating that magnetic zeolitic imidazolate framework 67/graphene oxide composites were feasible for analysis of trace analytes in environmental water samples. PMID- 28988437 TI - The Impact of Blamer-softening on Romantic Attachment in Emotionally Focused Couples Therapy. AB - Emotionally Focused Couples Therapy (EFT; Johnson, ) treats relationship distress by targeting couples' relationship-specific attachment insecurity. In this study, we used hierarchical linear modeling (Singer & Willett, ) to examine intercept and slope discontinuities in softened couples' trajectories of change in relationship satisfaction and relationship-specific attachment over the course of therapy from a total sample of 32 couples. Softened couples (n = 16) reported a significant increase in relationship satisfaction and a significant decrease in attachment avoidance at the softening session. Although softened couples displayed an initial increase in relationship-specific attachment anxiety at the softening session, their scores significantly decreased across post-softening sessions. Results demonstrated the importance of the blamer-softening change event in facilitating change in EFT. PMID- 28988438 TI - Long-term results of Amatsu tracheoesophageal shunt: Follow-up of more than 5 years. AB - BACKGROUND/OBJECTIVE: The Amatsu tracheoesophageal shunt (ATES) represents a nonprosthesis surgical option for voice restoration in laryngectomized patients. However, data regarding the long-term efficacy of ATES are lacking. STUDY DESIGN: Retrospective, single-institution study. METHODS: Between 2001 and 2010, 16 patients with laryngeal cancer underwent total laryngectomy with ATES at the Hyogo Cancer Center (Akashi, Hyogo, Japan). Of these, 11 achieved long-term tracheoesophageal speech that was maintained for a follow-up exceeding 5 years (range 75-161 months; median 95 months). All patients were male and ranged from 46 to 74 years of age at the time of ATES surgery. RESULTS: Of 11 eligible patients, eight were able to speak intelligibly with ATES at last follow-up. Regarding aspiration, three patients experienced no leakage, and six experienced mild leakage of saliva without medical intervention at last follow-up. Almost all patients maintained an unchanged degree of voice quality (9 of 11) and leakage (8 of 11). CONCLUSION: The favorable voice restoration and low aspiration rates achieved in this study appear to support the long-term efficacy of ATES. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:1395-1397, 2018. PMID- 28988440 TI - Immature platelet fraction in immune thrombocytopenia: Useful in diagnosis but does it predict bleeding? PMID- 28988439 TI - Rationale of the FIBROTARGETS study designed to identify novel biomarkers of myocardial fibrosis. AB - AIMS: Myocardial fibrosis alters the cardiac architecture favouring the development of cardiac dysfunction, including arrhythmias and heart failure. Reducing myocardial fibrosis may improve outcomes through the targeted diagnosis and treatment of emerging fibrotic pathways. The European-Commission-funded 'FIBROTARGETS' is a multinational academic and industrial consortium with the main aims of (i) characterizing novel key mechanistic pathways involved in the metabolism of fibrillary collagen that may serve as biotargets, (ii) evaluating the potential anti-fibrotic properties of novel or repurposed molecules interfering with the newly identified biotargets, and (iii) characterizing bioprofiles based on distinct mechanistic phenotypes involving the aforementioned biotargets. These pathways will be explored by performing a systematic and collaborative search for mechanisms and targets of myocardial fibrosis. These mechanisms will then be translated into individualized diagnostic tools and specific therapeutic pharmacological options for heart failure. METHODS AND RESULTS: The FIBROTARGETS consortium has merged data from 12 patient cohorts in a common database available to individual consortium partners. The database consists of >12 000 patients with a large spectrum of cardiovascular clinical phenotypes. It integrates community-based population cohorts, cardiovascular risk cohorts, and heart failure cohorts. CONCLUSIONS: The FIBROTARGETS biomarker programme is aimed at exploring fibrotic pathways allowing the bioprofiling of patients into specific 'fibrotic' phenotypes and identifying new therapeutic targets that will potentially enable the development of novel and tailored anti fibrotic therapies for heart failure. PMID- 28988441 TI - A prospective crossover trial of botulinum toxin chemodenervation versus injection augmentation for essential voice tremor. AB - OBJECTIVES/HYPOTHESIS: Botulinum toxin chemodenervation (BTX) is used to treat essential voice tremor (EVT), but results are not uniformly satisfactory. This study sought to assess the comparative utility of injection augmentation (IA) for EVT. STUDY DESIGN: Prospective crossover treatment study. METHODS: Patients with EVT underwent BTX. After washout patients underwent IA. Multidimensional assessment carried out prior to and 30 days after each treatment included 1) videostroboscopy graded by the Vocal Tremor Scoring System (VTSS), 2) acoustic and aerodynamic assessment (cepstral peak prominence, cepstral spectral index of dysphonia, cepstral peak prominence fundamental frequency, airflow, peak air pressure and intensity, maximum phonation time, and amplitude/frequency of tremor), 3) audio-perceptual assessment via Consensus Audio-Perceptual Evaluation of Voice (CAPE-V), and 4) patient self-assessment via Voice Handicap Index-10 (VHI-10) and Percent of Normal Function (PNF) scale. Findings were analyzed via paired t tests and Wilcoxon rank sum tests. RESULTS: Seven patients (five female and two male; mean age 67 years old; range, 46-82 years old) participated. VTSS grading showed divergent outcomes for certain individual sites of tremor, but without significant differences. Airflow increased following BTX and decreased following IA, and VHI-10 scores indicated slight improvement post-BTX (26.29 23.57), and decline post-IA (25.86-29.86), although differences were not significant. Only changes in audio-perceptual ratings of loudness achieved significance, which decreased with BTX and increased with IA. Five patients chose to resume BTX; two elected long-term IA. No findings supported patient preferences. CONCLUSIONS: IA demonstrated no advantage over BTX in the treatment of EVT. LEVEL OF EVIDENCE: 2b. Laryngoscope, 128:437-446, 2018. PMID- 28988442 TI - Dramatic response to nivolumab in xeroderma pigmentosum skin tumor. AB - We report the case of a 6-year-old female with xeroderma pigmentosum (XP) who developed a nonoperable scalp tumor, treated with anti-programmed cell death protein 1 (anti-PD-1) therapy (nivolumab). She presented with a sarcomatoid carcinoma of the scalp with bone lysis as well as vascular and meningeal contact. Nivolumab was initiated because it has emerged as a promising immunotherapy. We observed a dramatic tumor response with excellent tolerance. However, while on nivolumab therapy she developed two large skin melanomas and several squamous cell carcinomas, which have been resected. These results demonstrate that cancer immunotherapy in patients with XP can be impressive but complex and warrants further investigation. PMID- 28988444 TI - Usefulness of epicardial impedance evaluation for epicardial mapping and determination of epicardial ablation site for ventricular tachycardia: A pilot study. AB - BACKGROUND: During epicardial mapping, determination of appropriate ablation sites in low voltage areas (LVA) is challenging because of large epicardial areas covered by adipose tissue. OBJECTIVE: To evaluate the impedance difference between epicardial fat and the epicardial LVA using multiple detector computed tomography (MDCT). METHODS: We enrolled patients who underwent ventricular tachycardia (VT) ablation via the epicardial approach after endocardial ablation failure. After the procedure, MDCT-derived images of epicardial fat were loaded to the mapping system. Then, all points acquired during sinus rhythm were retrospectively superimposed and analyzed. RESULTS: This study included data from 7 patients (62.5 +/- 3.9 years old) who underwent eight epicardial VT ablation procedures. After the procedure, MDCT-derived images of epicardial fat were registered in eight procedures. Retrospective analysis of 1,595 mapping and 236 ablation points was performed. Of the 1,595 mapping points on the merged electroanatomical and epicardial fat maps, normal voltage area (NVA) and low voltage area (LVA) without fat had lower impedance than those with fat (NVA without fat 182 +/- 46 Omega vs. NVA with fat 321 +/- 164.0 Omega, P = 0.001, LVA without fat 164 +/- 69 Omega vs. LVA with fat 248 +/- 89 Omega, P = 0.002). Of the 236 ablation points, initial impedance before ablation was higher on epicardial fat than on epicardial LVA without fat (134 +/- 16 Omega vs. 156 +/- 28 Omega, P = 0.01). CONCLUSIONS: Real time epicardial impedance evaluation may be useful to determine effective epicardial ablation sites and avoid adipose tissue. However, the number of patients in the present study is limited. Further investigation with a large number of patients is needed to confirm our result. PMID- 28988443 TI - Effects of supramaximal balloon dilatation pressures on adult cricoid and tracheal cartilage: A cadaveric study. AB - OBJECTIVES/HYPOTHESIS: Cricoid fracture is a serious concern for balloon dilatation in airway stenosis. Furthermore, there are no studies examining tracheal rupture in balloon dilatation of stenotic segments. The aim of this study was to evaluate the effect of supramaximal pressures of balloons on the cricoid and tracheal rings. STUDY DESIGN: Prospective cadaveric study. METHODS: Seven cadaveric laryngotracheal complexes of normal adults with intact cricothyroid membranes were acquired. Noncompliant vascular angioplasty balloons (BARD-VIDA) were used for dilatation. The subglottis and trachea were subjected to supramaximal dilatation pressures graduated to nominal burst pressure (NBP) and, if necessary, rated burst pressure (RBP). Larger-diameter balloons, starting from 18 mm size to 24 mm, were used. Dilatations were maintained for 3 minutes. RESULTS: The cricoid ring was disrupted by larger-diameter balloons (22 mm and 24 mm) even at lower pressures (less than NBP) in six cases. Tracheal cartilages were very distensible, and external examination after supramaximal dilatation (24 mm close to RBP) revealed no obvious cartilage fractures or trachealis tears. Histopathological examination revealed sloughing of mucosa in the areas corresponding to balloon placement, but no microfractures or disruption of the perichondrium of tracheal ring cartilages. CONCLUSIONS: These results indicate that the cricoid is vulnerable to injury from larger balloons even at lower dilatation pressures. The tracheal cartilages and the membranous wall of the trachea remained resilient to supramaximal dilatation and larger balloons. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:1304-1309, 2018. PMID- 28988445 TI - Effect of cochlear implantation on middle ear function: A three-month prospective study. AB - OBJECTIVES/HYPOTHESIS: To determine if cochlear implantation has a delayed effect on the middle ear conductive hearing mechanism by measuring laser Doppler vibrometry (LDV) of the tympanic membrane (TM) in both implanted and contralateral control ears preoperatively and 3 months postoperatively, and then comparing the relative change in LDV outcome measures between implanted and control ears. STUDY DESIGN: Prospective cohort study. METHODS: Eleven preoperative adult unilateral cochlear implant recipients in previously unoperated ears with normal anatomy and aerated temporal bones were included in this study. The magnitude and phase angle of umbo velocity transfer function in response to air- conduction (AC) stimulus, and the magnitude of umbo velocity in response to bone- conduction (BC) stimulus were measured in the implant ear and the contralateral control ear preoperatively and 3 months postoperatively and compared. RESULTS: No significant changes in the magnitude or phase angle of TM velocity in response to either AC or BC stimulus were observed in the implanted ear relative to the contralateral control ear 3 months following cochlear implantation. CONCLUSIONS: From the results of LDV measurements, it can be said that cochlear implantation has no significant delayed effect on the middle ear conductive mechanism. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:1207-1212, 2018. PMID- 28988446 TI - Einthoven and electrical risk: Value of the electrocardiogram to predict sudden cardiac death. PMID- 28988447 TI - Online and call center referral for endocrine surgical pathology within institutions. AB - OBJECTIVES/HYPOTHESIS: We hypothesized that self-referred patients to academic centers will be equally distributed between general surgery and otolaryngology departments that perform thyroid surgery. We sought to quantify disparities in the assignment of these self-referred patients who may reach an institution through call centers or online pathways. STUDY DESIGN: Cross-sectional survey. METHODS: Key words "thyroid surgery" and "thyroid cancer" were used along with the name of the Accreditation Council for Graduate Medical Education-listed otolaryngology program in both Google and Bing search engines. The top three search results for departments were reviewed, and a tally was given to general surgery (GS), otolaryngology-head and neck surgery (OLHNS), or neither. A multidisciplinary center with both GS and OLHNS was recorded as "equitable." Telephone calls were tallied if they were directed to GS or OLHNS. RESULTS: Out of 400 program tallies, 117 (29.25%) patients were directed to GS and 50 (12.5%) were directed to OLHNS. An additional 181 (45.25%) were directed to neither group ("neither") (P < .05). Fifty-two (13%) of the patients were referred to multidisciplinary groups ("equitable"). A telephone call survey had 62 patients (62%) assigned to a general surgeon, as opposed to 38 (38%) for OLHNS (P < .05). Five institutions offered a multidisciplinary group when searching with Bing, and 11 were found by searching with Google. CONCLUSIONS: There is not an equal distribution of self-referred patients with thyroid surgical pathology. It may be important to increase the online presence of OLHNS surgeons who perform thyroid surgery at academic medical institutions. Multidisciplinary centers focused on thyroid and parathyroid surgical disease represents one model of assigning self referred patients. LEVEL OF EVIDENCE: NA Laryngoscope, 1977-1981, 2018. PMID- 28988448 TI - Clinical outcomes and prognostic factors of sialendoscopy in salivary duct stenosis. AB - OBJECTIVES/HYPOTHESIS: This study aimed to analyze the clinical outcomes of sialendoscopy in patients with salivary duct stenosis and to investigate factors associated therewith. STUDY DESIGN: Retrospective case series. METHODS: This study included 47 patients with salivary stenosis who underwent sialendoscopy between January 2014 and December 2015. Subjective symptom, salivary flow rate, salivary scintigraphy, and radiologic evaluation using magnetic resonance (MR) sialography were performed preoperatively; direct ductal findings were evaluated during sialendoscopy. Univariate and multivariate analyses of factors influencing the patient-reported outcomes (complete, partial, or no improvement at 3 months after sialendoscopy) were conducted. RESULTS: Stenosis severity was graded according to sialendoscopic findings. Seventeen patients were classified with grade I stenosis, 18 patients with grade II stenosis, and 12 patients with grade III stenosis. Symptoms completely disappeared in 21 patients (44.7%) after sialendoscopic procedures. In 19 patients (40.4%), symptoms were partially improved. Seven patients (14.9%) showed no improvement or worsening of symptoms. In univariate analysis, symptom score, stimulatory salivary flow rate, Tmin (time interval from stimulation to minimal count on salivary scintigraphy), type of stenosis on MR sialography, and sialendoscopic grade were found to be significantly associated with treatment outcomes. In multivariate analysis, Tmin , stenosis type of MR sialography, and sialendoscopic grade remained significantly associated with outcomes after sialendoscopy. CONCLUSIONS: Sialendoscopic procedures were found to be clinically satisfactory for relieving the symptoms of patients with salivary stenosis. Factors related to the severity of ductal stenosis such as Tmin , stenosis type of MR sialography, and sialendoscopic grade were significantly associated with the success of sialendoscopic treatment for salivary duct stenosis. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:878-884, 2018. PMID- 28988449 TI - Surfactant-assisted electromembrane extraction combined with cyclodextrin modified capillary electrophoresis for the separation and quantification of Tranylcypromine enantiomers in biological samples. AB - Surfactant-assisted electromembrane extraction coupled with cyclodextrin-modified capillary electrophoresis was developed for the separation and determination of Tranylcypromine enantiomers in biological samples. This combination would provide a new strategy for selective and sensitive determination of target analytes. The addition of surfactant in the donor solution improved the analyte transport into the lumen of hollow fiber that resulted in an enhancement in the analytes migration into acceptor solution. Optimization of the variables, affecting proposed method, was carried out and best results were achieved with a 175 V potential as driving force of the electromembrane extraction, 2 nitrophenyloctylether as the supported liquid membrane, donor solution containing 0.2 mM Triton X-100 with pH 3 and 0.1 M HCl for acceptor solution. Then, the extract was analyzed using cyclodextrin-modified capillary electrophoresis method for separation of Tranylcypromine enantiomers. The best results were obtained with a phosphate running buffer (100 mM, pH 2.0) containing 7% w/v hydroxypropyl alpha-cyclodextrin. Under the optimum conditions, a low limit of detection (3.03 ng/mL), good linearity (R2 > 0.9953), and relative standard deviations below 4.0% (n = 5) were obtained. Finally, this procedure was applied to determine the concentration of Tranylcypromine enantiomers in urine samples with satisfactory results. PMID- 28988450 TI - Feasibility of coronary angiography and percutaneous coronary intervention after transcatheter aortic valve replacement using a MedtronicTM self-expandable bioprosthetic valve. AB - BACKGROUND AND OBJECTIVE: With aging, the progression of atherosclerosis in the coronary arteries is expected. The MedtronicTM self-expandable aortic bioprosthetic valve is deployed in the supra-annular position, and it has been challenging to selectively engage coronary arteries post-transcatheter aortic valve replacement (TAVR) even though there are diamond-shaped spaces in the mesh frame within the valve. Given the scarcity of data, we analyzed angiographic and clinical data from all patients requiring coronary angiography (CA) or intervention post-TAVR. METHODS: From January 2012 to December 2016, 403 patients were treated for severe aortic stenosis with TAVR at our center using the MedtronicTM self-expandable valve. This study included patients who underwent CA with or without percutaneous coronary intervention (PCI) after TAVR. RESULTS: Twenty-eight patients underwent 43 CAs after TAVR at our institution. Eleven patients (39%) were women. More than 90% of the procedures were performed for acute coronary syndrome. Thirty-six cases were performed using the transfemoral approach (83%). Forty-two of 43 (97%) left coronary arteries were selectively engaged, and 29 of 32 (90%) right coronary arteries were selectively engaged. We were able to engage 11 saphenous vein grafts and two left internal mammary artery grafts selectively (100%). The mean fluoroscopy time for diagnostic CA was 11.5 min, and for PCI, instantaneous wave-free ratio, or intravascular ultrasound (IVUS) interrogation, it was 19 minutes. The mean amount of contrast used for diagnostic CA was 102 cc per case, and for PCI, iFR, or IVUS, it was 146 cc per case. No periprocedural complication was noted. CONCLUSIONS: CA with or without PCI after TAVR is feasible with supra-annular self-expandable valves. With the proper technique in experienced hands, it can be conducted safely. PMID- 28988451 TI - Evolving trends in sinus surgery: What is the impact of balloon sinus dilation? AB - OBJECTIVES/HYPOTHESIS: Balloon dilation (BD) represents a minimally invasive alternative to endoscopic sinus surgery (ESS). Although BD was introduced in 2006, distinct Current Procedural Terminology (CPT) codes were not available until 2011, making prior analysis of population-based trends difficult. Our objectives were to evaluate these trends and compare any changes to the use of traditional ESS techniques. Geographic trends also were evaluated. METHODS: Medicare Part B national datasets encompassing procedures from 2011 to 2015 were obtained. ESS CPT codes (frontal sinusotomy, maxillary antrostomy with/without tissue removal, sphenoidotomy) and BD codes were searched to determine temporal trends in their use. Additionally, state carriers were individually evaluated for geographic trends. RESULTS: National use of BD increased greater than five-fold (39,193 from 7,496 among Medicare patients), whereas the use of ESS increased by only 5.9%. This increase in BD was observed across all sites, including the sphenoid (7.0x), maxillary (5.1x), and frontal (4.7x) sinuses. In the most recent year for which data was available (2015), a significantly greater portion of sinus procedures in these sites utilized BD in the South (42.1%) compared to the Northeast (30.6%), West (29.5%), and Midwest (25.3%) regions (P < 0.0001). CONCLUSION: The performance of BD has increased markedly in recent years. Because the use of ESS codes remain stable, observed BD trends are unlikely to be due simply to greater familiarity with newer CPT coding. The reasons for the striking increase in BD popularity are speculative and beyond the scope of this analysis, but further study may be needed. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:1299 1303, 2018. PMID- 28988452 TI - Immobilized-enzyme reactors integrated with capillary electrophoresis for pharmaceutical research. AB - Enzymes play an essential role in many aspects of pharmaceutical research as drug targets, drug metabolizers, enzyme drugs and more. In this specific field, enzyme assays are required to meet a number of specific requirements, such as low cost, easy automation, and high reliability. The integration of an immobilized-enzyme reactor to capillary electrophoresis represents a unique approach to fulfilling these criteria by combining the benefits of enzyme immobilization, that is, increased stability and repeated use, as well as the minute sample consumption, short analysis time, and efficient analysis provided by capillary electrophoresis. In this review, we summarize, analyze, and discuss published works where pharmaceutically relevant enzymes were used to prepare capillary electrophoresis-integrated immobilized-enzyme reactors in an online manner. The presented assays are divided into three distinct groups based on the drug-enzyme relationship. The first, more extensively studied group employs enzymes that are considered to be therapeutic targets, the second group of assays present tools to assess drug metabolism and the third group assesses enzyme drugs. Furthermore, we examine various methods of enzyme immobilization and their implications for assay properties. PMID- 28988453 TI - The structure of InAlGaN layers grown by metal organic vapour phase epitaxy: effects of threading dislocations and inversion domains from the GaN template. AB - Defects in quaternary InAlGaN barriers and their effects on crystalline quality and surface morphology have been studied. In addition to growth conditions, the quality of the GaN template may play an important role in the formation of defects in the barrier. Therefore, this work is focused on effects caused by threading dislocations (TDs) and inversion domains (IDs) originating from the underlying GaN. The effects are observed on the crystalline quality of the barrier and characteristic surface morphologies. Each type of TDs is shown to affect the surface morphology in a different way. Depending on the size of the corresponding hillock for a given pinhole, it was possible to determine the dislocation type. It is pointed out that the smallest pinholes are not connected to TDs whereas the large ones terminate either mixed type or edge type TDs. At sufficiently large layer thickness, the IDs originating from the GaN template lead to the formation of concentric trenches at the layer surface, and this is related to the change in growth kinetics on top and at the immediate surroundings of the ID. PMID- 28988454 TI - Awake serial intralesional steroid injections without surgery as a novel targeted treatment for idiopathic subglottic stenosis. AB - OBJECTIVES/HYPOTHESIS: The fibrotic/erythematous appearance of the subglottis in idiopathic subglottic stenosis (iSGS) hints that it might respond to repeated intralesional steroid treatment similar to keloids. STUDY DESIGN: Retrospective cohort study. METHODS: Thirteen iSGS subjects (six treated in-office with serial intralesional steroid injections [SILSI] versus seven treated endoscopically in the operating room [OR] followed by awake SILSI) between October 2011 and April 2017. Forced spirometry was performed before injections and at each follow-up visit (peak expiratory flow [%PEF] and peak inspiratory flow). Steroids were injected via transcricothyroid or transnasal routes. Injections were grouped into rounds of four to six injections separated by 3 to 5 weeks. RESULTS: Thirteen subjects with a mean follow-up of 3 years (3.3 years for SILSI and 2.7 years for OR). Awake-only SILSI subjects had a mean improvement/round of 23.1% %PEF (range, 65.4%-88.6%), whereas the OR-treated subjects had a mean %PEF improvement/round of 25.1% (range, 57.4%-82.5%). Both groups had improved breathing, and the improvements were statistically equal (P = .569). SILSI subjects underwent 5.3 injections/round in 1.3 rounds, whereas OR subjects had 5.9 injections/round over 2.1 rounds. Statistically significant improvement was seen in %PEF for both groups (SILSI P = .007, OR P = .002). Overall, SILSI achieved sustained %PEF above 80% in 83% (5/6) and OR + SILSI 86% (6/7). CONCLUSIONS: SILSI in the awake outpatient setting can improve the airway caliber in iSGS and is equivalent to endoscopic OR treatment. We believe iSGS can be viewed as a chronic scarring/inflammatory condition that can benefit from steroid scar-modification therapy. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:610-617, 2018. PMID- 28988455 TI - Safety profiles of percutaneous left atrial appendage closure devices: An analysis of the Food and Drug Administration Manufacturer and User Facility Device Experience (MAUDE) database from 2009 to 2016. AB - BACKGROUND: Percutaneous left atrial appendage closure (LAAC) is a viable option for AF patients who are unable to tolerate long-term oral anticoagulation (OAC). OBJECTIVE: We sought to assess the safety of two commonly used percutaneous devices for LAA closure in the United States by analysis of surveillance data from the FDA Manufacturer and User Facility Device Experience (MAUDE) database. METHODS: The MAUDE database was queried between May 1, 2006 and May 1, 2016 for LARIAT(r) (SentreHEART Inc., Redwood City, CA, USA) and WATCHMANTM (Boston Scientific Corp., Marlborough, MA, USA) devices. Among 622 retrieved medical device reports, 356 unique and relevant reports were analyzed. The cumulative incidence of safety events was calculated over the study period and compared between the two devices. RESULTS: LAAC was performed with LARIAT in 4,889 cases. WATCHMAN was implanted in 2,027 patients prior to FDA approval in March 2015 and 3,822 patients postapproval. The composite outcome of stroke/TIA, pericardiocentesis, cardiac surgery, and death occurred more frequently with WATCHMAN (cumulative incidence, 1.93% vs. 1.15%; P = 0.001). The same phenomenon was observed when comparing the WATCHMAN pre- and postapproval experiences for the composite outcome, as well as device embolization, cardiac surgery, and myocardial infarction. CONCLUSIONS: MAUDE-reported data show that postapproval, new technology adoption is fraught with increased complications. Improved collaboration between operators, device manufacturers, and regulators can better serve patients through increased transparency and practical postmarket training and monitoring mechanisms. PMID- 28988457 TI - Re-evaluating pathogenicity of variants associated with the long QT syndrome. AB - INTRODUCTION: Genetic testing for congenital long QT syndrome (LQTS) has become common. Recent studies have shown that some variants labelled as pathogenic might be misclassified due to sparse case reports and relatively common allele frequencies (AF) in the general population. This study aims to evaluate the presence of LQTS-associated variants in the Genome Aggregation Database (gnomAD) population, and assess the functional impact of these variants. METHODS AND RESULTS: Variants associated with LQTS from the Human Gene Mutation Database were extracted and matched to the gnomAD to evaluate population-based AF. We used MetaSVM to predict the function of LQTS variants. Allele distribution by protein topology in KCNQ1, KCNH2, and SCN5A was compared between gnomAD (n = 123,136) and a cohort of LQTS patients aggregated from eight published studies (n = 2,683). Among the 1,415 LQTS-associated single nucleotide variants in 30 genes, 347 (25%) are present in gnomAD; 24% of the 347 variants were predicted as functionally tolerated compared with 4% of variants not present in gnomAD (P < 0.001). Of the 347 pathogenic variants in gnomAD, seven (2%) had an AF of >= 0.001 and 65 (19%) variants had an AF of >= 0.0001. In KCNQ1, KCNH2, and SCN5A, allele distribution by protein functional region was significantly different with gnomAD alleles appearing less frequently in highly pathogenic domains than case alleles. CONCLUSION: A significant number of LQTS variants have insufficient evidence for pathogenicity and relatively common AF in the general population. Caution should be used when ascribing pathogenicity to these variants. PMID- 28988456 TI - Electrocardiographic features of failed and recurrent right ventricular outflow tract catheter ablation of idiopathic ventricular arrhythmias. AB - INTRODUCTION: Various ECG algorithms have been proposed to identify the origin of idiopathic outflow tract (OT)-ventricular arrhythmia (VA). However, electrocardiographic features of failed and recurrent right ventricular outflow tract (RVOT) ablation of idiopathic OT-VAs have not been clearly elucidated. METHODS AND RESULTS: A total of 264 consecutive patients (mean age: 44.0 +/- 13.0 years, 96 male) undergoing RVOT ablation for OT-VAs with a transition >=V3 , including 241 patients (91.6%) with initially successful procedures and 23 patients (8.4%) with failed ablation. Detailed clinical characteristics and ECG features were analyzed and compared between the two groups. VAs with failed RVOT ablation had larger peak deflection index (PDI), longer V2 R wave duration (V2 Rd), smaller V2 S wave amplitude, higher R/S ratio in V2 , higher V3 R wave amplitude, and larger V2 transition ratio than those with successful ablation. Multivariate analysis demonstrated that PDI, V2 Rd, V2 transition ratio, and pacemapping score acquired during mapping independently predicted failed ablation (P = 0.01, P = 0.01, P = 0.01, and P < 0.001, respectively). In 31 recurrent cases (12.8%) after initially successful ablation, multivariate Cox regression analysis showed that only the earliest activation time acquired during mapping predicted the recurrences after successful ablation (P = 0.001). The recurrent cases displayed different ECG features comparing with those with failed ablation. CONCLUSION: The electrocardiographic features of failed RVOT ablation of idiopathic OT-VAs with a transition >=V3 were characterized by PDI, V2 Rd, V2 transition ratio, and pacemapping score acquired during mapping, unlike the recurrent RVOT ablation. PMID- 28988458 TI - Malignant fibrous histiocytoma: Database review suggests a favorable prognosis in the head and neck. AB - OBJECTIVE: The malignant fibrous histiocytoma (MFH) is the most common soft tissue sarcoma of the head and neck. Currently, most of the data on this tumor relies on small retrospective studies. The objective of this study is to use the Surveillance, Epidemiology, and End Results (SEER) database to compare characteristics of this tumor based on location to better understand its prognosis in the head and neck region. This article represents the largest study analyzing prognosis of this tumor in the head and neck to date. STUDY DESIGN: Retrospective analysis of SEER database. METHODS: Using the SEER database, 395 patients with MFH of the head and neck were compared with 3,968 patients with MFH of the trunk and extremities. Disease-specific survival was carried out comparing these two cohorts, as well as univariate and multivariate analysis to determine hazard ratios. RESULTS: Head and neck MFH had a significantly higher disease specific survival compared with trunk and extremity disease. However, head and neck tumors were more frequently a smaller size (P < .0001) and lower grade (P < .0001). Larger tumors and grade III and IV tumors conferred a worse prognosis (P < .0001). CONCLUSION: Head and neck malignant fibrous histiocytoma presents at a smaller size and lower grade, likely due to earlier presentation in this region. Because of this, head and neck malignant fibrous histiocytoma represents a more favorable survival prognosis compared with trunk and extremity disease. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:885-888, 2018. PMID- 28988459 TI - Inconsistency in classifying vascular anomalies: What's in a name? AB - BACKGROUND: Vascular anomalies are a heterogeneous group of disorders seen in children and adults. A standard nomenclature for classification has been offered by the International Society for the Study of Vascular Anomalies. Its application is important for communication among the multiple specialties involved in the care of patients and for planning treatment, as well as for research and billing. We hypothesized that terminology still is not uniformly applied, and that this could have an impact on treatment. METHODS: We retrospectively reviewed the medical records of patients with nonbrain lesions from our institutional vascular anomalies database seen during 2010-2016 for whom at least one clinic visit, radiologic imaging report, and pathology report were available to compare diagnoses among and within disciplines, and treatment recommendations. Diagnoses and referral patterns by community healthcare providers were also reviewed. RESULTS: Of 400 patients seen during the targeted time interval, 35 had clinical, imaging, and pathology reports. Agreement in terminology from initial clinic notes with imaging and pathology reports was noted in only three cases (9%). "Hemangioma" was often misused; "lymphangioma" and "cystic hygroma" persist as diagnostic labels. Community healthcare providers referred vascular malformations with a diagnosis of "mass" or "hemangioma" in 17 of 18 cases where that information was available. Incomplete or mislabeling of vascular anomalies sometimes delayed referrals to appropriate clinics, though it did not have a major impact on treatment. CONCLUSIONS: An understanding of vascular anomalies as tumors or malformations is not uniform. Ongoing education will be needed to promote consensus terminology and facilitate referrals. PMID- 28988460 TI - Toolbox of assessment tools of technical skills in otolaryngology-head and neck surgery: A systematic review. AB - OBJECTIVE: To support the development of programs of assessment of technical skills in the operating room (OR), we systematically reviewed the literature to identify assessment tools specific to otolaryngology-head and neck surgery (OTL HNS) core procedures and summarized their characteristics. METHODS: We systematically searched Embase, MEDLINE, PubMed, and Cochrane to identify and report on assessment tools that can be used to assess residents' technical surgical skills in the operating room for OTL-HNS core procedures. RESULTS: Of the 736 unique titles retrieved, 16 articles met inclusion criteria, covering 11 different procedures (in otology, rhinology, laryngology, head and neck, and general otolaryngology). The tools were composed of a task-specific checklist and/or global rating scale and were developed in the OR, on human cadavers, or in a simulation setting. CONCLUSIONS: Our study reports on published tools for assessing technical skills for OTL-HNS residents during core procedures conducted in the OR. These assessment tools could facilitate the provision of timely feedback to trainees including specific goals for improvement. However, the paucity of publications suggests little agreement on how to best perform work based direct-observation assessment for core surgical procedures in OTL-HNS. The sparsity of tools specific to OTL-HNS may become a barrier to a fluid transition to competency-based medical education. Laryngoscope, 128:1571-1575, 2018. PMID- 28988461 TI - Number of theoretical plates achievable by a toroidal capillary electrophoresis system. AB - The ability of a method and instrument to separate very similar compounds is related to the "plate number," a number indicating performance. The resolution between two neighboring peaks is proportional to the square root of the plate number. Currently available commercial capillary electrophoresis instruments easily reach plate numbers of a few million. In the present work, a capillary electrophoresis system with a toroidal platform is proposed and theoretically studied with the goal of extending the achievable plate number. In this new system, electrophoresis occurs in a nonstop continuous circulating mode within a closed loop capillary (toroid). Plate numbers upwards of one billion are theoretically predicted. This could resolve hundreds of unseparated mixtures of stereoisomers and other analytes that remain without a method for their analysis. PMID- 28988462 TI - Exploring the dark side of left atrial appendage closure devices. PMID- 28988463 TI - Evidence against the mucosal traction theory in cholesteatoma. AB - OBJECTIVES: To investigate the distribution of ciliated epithelium in the human middle ear and its potential role in the formation of cholesteatoma. STUDY DESIGN: Comparative human temporal bone study. METHODS: We selected temporal bones from 14 donors with a diagnosis of cholesteatoma, 15 with chronic otitis media without retraction pockets, 14 with chronic otitis media with retraction pockets, 14 with cystic fibrosis (CF), and 16 controls. We mapped the distribution of the ciliated cells in the mucosal lining of the middle ear and tympanic membrane using three-dimensional reconstruction analysis, and counted the number of ciliated cells in the middle ear mucosa. RESULTS: Ciliated cells are extremely sparse in the epithelial lining of the lateral surface of the ossicles in the epitympanum and the medial surface of the tympanic membrane. Furthermore, there is a significant decrease in the number of ciliated cells in these areas in temporal bones with cholesteatoma, chronic otitis media, chronic otitis media with retraction pockets, and CF compared to controls. Ciliated cells most commonly are located at the hypotympanum and the Eustachian tube opening but not the tympanic membrane or epitympanum. CONCLUSION: The paucity of ciliated epithelial cells on the medial side of the tympanic membrane and the lateral surface of the ossicles in the epitympanum in cases with cholesteatoma and/or chronic otitis media do not support the mucosal migration theory of cholesteatoma formation. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:1663-1667, 2018. PMID- 28988464 TI - Development and evaluation of microwave-assisted and ultrasound-assisted methods based on a quick, easy, cheap, effective, rugged, and safe sample preparation approach for the determination of bisphenol analogues in serum and sediments. AB - Microwave- and ultrasound-assisted methods based on a quick, easy, cheap, effective, rugged, and safe sample preparation approach followed by high performance liquid chromatography with tandem mass spectrometry were developed for the simultaneous determination of eight bisphenol analogues in serum and sediment. The developed methods provided satisfactory extraction efficiency for the energy provided by microwaves and ultrasound. Compositions of commercial sorbents (primary secondary amine, MgSO4 , octadecyl-modified silica, and graphitized carbon black) were evaluated. The ultrasound-assisted method was suited for serum using primary secondary amine, MgSO4 , and octadecyl-modified silica as sorbents and a mixture of hexane and ethyl acetate as extraction solvent. The microwave-assisted method worked better for sediment with tetrahydrofuran and methanol as solvents and primary secondary amine, MgSO4 , octadecyl-modified silica, and graphitized carbon black as sorbents. Other experimental parameters, such as extraction temperature and time, were also optimized. The inter- and intraday relative standard deviations ranged from 2.7 to 5.5%. The limits of detection were between 0.1 and 1.0 ng/mL for serum and between 0.1 and 0.5 ng/g dry weight for sediment. The proposed methods were successfully applied to seven sediment and 20 human serum samples. The results showed that the developed methods were practical for the analysis and biomonitoring of bisphenols in sera and sediment. PMID- 28988466 TI - Characterization of ancient lipids in prehistoric organic residues: Chemical evidence of livestock-pens in rock-shelters since early neolithic to bronze age. AB - The characterization of ancient lipids from prehistoric sediments (fumiers) located in a rock-selter has been possible after the optimization of an analytical method based on the microwave-assisted extraction and solid-phase extraction clean-up step and a final derivatization step followed by gas chromatography with mass spectrometry. Eight sterols and two bile acids were detected just in the partially burned and unburned layers of the fumiers (animal organic residues deriving from manure/dung). The relationship between some of these compounds can be used to distinguish the biogenic origin of the samples, concluding that these strata (from Early Neolithic to Late Chalcolithic/Early Bronze Age) can be classified as ruminant residues. Three main periods of activity are observed over a period of 2000 years: one from 3990 +/- 40 before present (4530-4410 calibrated before present) to 4100 +/- 40 before present (4820 4750/4730-4510/4470-4450 calibrated before present), the second from 4470 +/- 40 before present (5300-4970 calibrated before present) to 5490 +/- 30 before present (6310-6275/6230-6220 calibrated before present) and the third from 5880 +/- 30 before present (6775-6765/6750-6645 calibrated before present) to 6010 +/- 30 before present (6940-6780/6765-6755 calibrated before present). Chemical data obtained are in concordance with the previous results obtained in the area. PMID- 28988465 TI - Outcomes and reliability of the flow coupler in postoperative monitoring of head and neck free flaps. AB - OBJECTIVES/HYPOTHESIS: To assess the accuracy and reliability of the flow coupler relative to the implantable arterial Doppler probe in postoperative monitoring of head and neck free flaps. STUDY DESIGN: Retrospective single-institution study, April 2015 to March 2017. METHODS: Both the venous flow coupler and arterial Doppler were employed in 120 consecutive head and neck free flap cases. When Doppler signal loss occurred, flaps were evaluated by physical exam to determine whether signal loss was a true positive necessitating operating room takeback. Sensitivity, specificity, and false positive rate (FPR) were recorded for each device. Logistic regression was conducted to identify user trends over time. RESULTS: Eleven of 120 patients (9.2%) required takeback, 10 from venous thrombosis and one from arterial thrombosis. Permanent signal loss (PSL) occurred in the flow coupler in all takebacks; PSL occurred in the arterial Doppler only in the case of arterial thrombosis. Salvage rate was 9/11 (81.8%). For the flow coupler, sensitivity was 100%, specificity 86.4%, and FPR 13.6%. For the arterial probe, sensitivity was 9.1%, specificity 97.1%, and FPR 2.9%. A 4.1% decrease in false positives with each additional flow coupler use was observed. CONCLUSIONS: Monitoring the vein via flow coupler has high sensitivity in identifying vascular compromise compared to the arterial probe, especially for venous thrombosis. There is moderate FPR; this decreases with increased usage and, when supplemented with physical examination, does not result in unnecessary takebacks. The flow coupler can be a valuable tool in postoperative monitoring of head and neck free flaps. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:812-817, 2018. PMID- 28988467 TI - What antibiotic should be used in the management of an otherwise healthy adult with a peritonsillar abscess? PMID- 28988468 TI - Thermal latency adds to lesion depth after application of high-power short duration radiofrequency energy: Results of a computer-modeling study. AB - INTRODUCTION: The use of ultra-short RF pulses could achieve greater lesion depth immediately after the application of the pulse due to thermal latency. METHODS AND RESULTS: A computer model of irrigated-catheter RF ablation was built to study the impact of thermal latency on the lesion depth. The results showed that the shorter the RF pulse duration (keeping energy constant), the greater the lesion depth during the cooling phase. For instance, after a 10-second pulse, lesion depth grew from 2.05 mm at the end of the pulse to 2.39 mm (17%), while after an ultra-short RF pulse of only 1 second the extra growth was 37% (from 2.22 to 3.05 mm). Importantly, short applications resulted in deeper lesions than long applications (3.05 mm vs. 2.39 mm, for 1- and 10-second pulse, respectively). While shortening the pulse duration produced deeper lesions, the associated increase in applied voltage caused overheating in the tissue: temperatures around 100 degrees C were reached at a depth of 1 mm in the case of 1- and 5-second pulses. However, since the lesion depth increased during the cooling period, lower values of applied voltage could be applied in short durations in order to obtain lesion depths similar to those in longer durations while avoiding overheating. CONCLUSION: The thermal latency phenomenon seems to be the cause of significantly greater lesion depth after short-duration high power RF pulses. Balancing the applied total energy when the voltage and duration are changed is not the optimal strategy since short pulses can also cause overheating. PMID- 28988469 TI - Treatment, survival, and costs of oropharyngeal cancer care in the elderly. AB - OBJECTIVES/HYPOTHESIS: To examine associations between treatment, survival, and costs in elderly patients with oropharyngeal squamous cell cancer (OPSCC). STUDY DESIGN: Retrospective cross-sectional analysis of Surveillance, Epidemiology, and End Results-Medicare data. METHODS: We evaluated 666 patients diagnosed with OPSCC from 2004 to 2007 using cross-tabulations, multivariate logistic and generalized linear regression modeling, and survival analysis. RESULTS: The majority of patients were nonsmokers (79%), had advanced-stage disease (59%), and received chemoradiation (38%) or radiation (28%). Surgery with postoperative radiation (hazard ratio [HR]: 0.33 [95% CI: 0.20-0.53]) and chemoradiation (HR: 0.45 [95% CI: 0.29-0.71]) were associated with improved survival, whereas stage IV disease was associated with poorer survival (HR: 1.95 [95% CI: 1.13-3.38]). Additional cancer-directed treatment after primary treatment was more likely following chemoradiation (odds ratio [OR]: 3.44 [95% CI: 1.78-6.63]). Salvage surgery was performed in 25% of patients undergoing subsequent additional cancer directed treatment, and was associated with high-volume hospitals (OR: 2.81 [95% CI: 1.07-7.74]). Additional radiation (HR: 0.47 [95% CI: 0.31-0.72]) and salvage surgery (HR: 0.61 [95% CI: 0.38-0.99]) were associated with improved overall survival when performed >6 months following initial treatment, whereas salvage neck dissection alone was not significantly associated with survival after controlling for time to salvage (HR: 0.38 [95% CI: 0.05-2.78]). Treatment and 5 year overall costs were highest for chemoradiation, surgery with postoperative radiation, and additional cancer-directed treatment. CONCLUSIONS: Multimodality treatment in elderly OPSCC patients was associated with improved survival and increased costs. Chemoradiation was associated with an increased likelihood of additional cancer-directed treatment. Salvage surgery was centralized at high volume hospitals, and was associated with improved survival when performed >6 months after last initial treatment date, but was performed in <20% of patients undergoing additional treatment. LEVEL OF EVIDENCE: 2c. Laryngoscope, 128:1103 1112, 2018. PMID- 28988470 TI - El Nino Southern Oscillation influences the abundance and movements of a marine top predator in coastal waters. AB - Large-scale climate modes such as El Nino Southern Oscillation (ENSO) influence population dynamics in many species, including marine top predators. However, few quantitative studies have investigated the influence of large-scale variability on resident marine top predator populations. We examined the effect of climate variability on the abundance and temporary emigration of a resident bottlenose dolphin (Tursiops aduncus) population off Bunbury, Western Australia (WA). This population has been studied intensively over six consecutive years (2007-2013), yielding a robust dataset that captures seasonal variations in both abundance and movement patterns. In WA, ENSO affects the strength of the Leeuwin Current (LC), the dominant oceanographic feature in the region. The strength and variability of the LC affects marine ecosystems and distribution of top predator prey. We investigated the relationship between dolphin abundance and ENSO, Southern Annular Mode, austral season, rainfall, sea surface salinity and sea surface temperature (SST). Linear models indicated that dolphin abundance was significantly affected by ENSO, and that the magnitude of the effect was dependent upon season. Dolphin abundance was lowest during winter 2009, when dolphins had high temporary emigration rates out of the study area. This coincided with the single El Nino event that occurred throughout the study period. Coupled with this event, there was a negative anomaly in SST and an above average rainfall. These conditions may have affected the distribution of dolphin prey, resulting in the temporary emigration of dolphins out of the study area in search of adequate prey. This study demonstrated the local effects of large-scale climatic variations on the short-term response of a resident, coastal delphinid species. With a projected global increase in frequency and intensity of extreme climatic events, resident marine top predators may not only have to contend with increasing coastal anthropogenic activities, but also have to adapt to large scale climatic changes. PMID- 28988471 TI - EMG disease in a pediatric patient. PMID- 28988472 TI - Quantitative Determination of Bulk Molecular Concentrations of beta-Agonists in Pork Tissue Samples by Direct Internal Extractive Electrospray Ionization-Mass Spectrometry. AB - Rapid quantitative determination of bulk molecular concentration in solid samples without sample pretreatment is demonstrated using the internal extractive electrospray ionization-mass spectrometry (iEESI-MS) analysis of six beta agonists, including salbutamol (Sal), clenbuterol (Cle), ractopamine (Rac), terbutaline (Ter), tulobuterol (Tul), brombuterol (Bro), in pork tissue samples. Single sample analysis only required 1 min. The linear range of detection was about 0.01-1000 MUg/kg (R2 > 0.9994). The limit-of-detection (LOD) varied from 0.002 MUg/kg for Sal to 0.006 MUg/kg for Tul. Relative standard deviation (RSD) of quantitation was in the range 6.5-11.3%. The analytical results were validated by gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography-mass spectrometry (LC-MS), showing the accuracy rates of 92-105%. The current study extends the power of ambient MS as a method for the quantification of molecules at the surface of solid samples (e.g., in MUg/cm2 units) toward the quantification of molecules in bulk sample volume (i.e., in MUg/kg units), which is commonly required in food safety control, biomedical analysis, public security, and many other disciplines. PMID- 28988473 TI - Preparation, Properties, and Structures of the Radical Anions and Dianions of Azapentacenes. AB - A series of diazapentacenes (5,14-diethynyldibenzo[b,i]phenazine, 6,13 diethynylnaphtho[2,3-b]phenazine) and tetraazapentacenes (7,12 diethynylbenzo[g]quinoxalino[2,3-b]quinoxaline, 6,13-diethynylquinoxalino[2,3 b]phenazine) were reduced to their radical anions and dianions, employing either potassium anthracenide or lithium naphthalenide in THF. The anionic species formed were investigated by UV-vis-NIR, fluorescence and EPR spectroscopy, spectroelectrochemistry, and quantum chemical calculations. Single crystal X-ray structures of three of their radical anions and of three of their dianions were obtained. In contrast to the acenes, the anions of the azapentacenes are persistent and, in some cases, even moderately stable toward air, and were characterized. PMID- 28988474 TI - Electrochemical CO2 Reduction over Compressively Strained CuAg Surface Alloys with Enhanced Multi-Carbon Oxygenate Selectivity. AB - The electrochemical reduction of carbon dioxide using renewably generated electricity offers a potential means for producing fuels and chemicals in a sustainable manner. To date, copper has been found to be the most effective catalyst for electrochemically reducing carbon dioxide to products such as methane, ethene, and ethanol. Unfortunately, the current efficiency of the process is limited by competition with the relatively facile hydrogen evolution reaction. Since multi-carbon products are more valuable precursors to chemicals and fuels than methane, there is considerable interest in modifying copper to enhance the multi-carbon product selectivity. Here, we report our investigations of electrochemical carbon dioxide reduction over CuAg bimetallic electrodes and surface alloys, which we find to be more selective for the formation of multi carbon products than pure copper. This selectivity enhancement is a result of the selective suppression of hydrogen evolution, which occurs due to compressive strain induced by the formation of a CuAg surface alloy. Furthermore, we report that these bimetallic electrocatalysts exhibit an unusually high selectivity for the formation of multi-carbon carbonyl-containing products, which we hypothesize to be the consequence of a reduced coverage of adsorbed hydrogen and the reduced oxophilicity of the compressively strained copper. Thus, we show that promoting copper surface with small amounts of Ag is a promising means for improving the multi-carbon oxygenated product selectivity of copper during electrochemical CO2 reduction. PMID- 28988475 TI - Nanoscale Coloristic Pigments: Upper Limits on Releases from Pigmented Plastic during Environmental Aging, In Food Contact, and by Leaching. AB - The life cycle of nanoscale pigments in plastics may cause environmental or human exposure by various release scenarios. We investigated spontaneous and induced release with mechanical stress during/after simulated sunlight and rain degradation of polyethylene (PE) with organic and inorganic pigments. Additionally, primary leaching in food contact and secondary leaching from nanocomposite fragments with an increased surface into environmental media was examined. Standardized protocols/methods for release sampling, detection, and characterization of release rate and form were applied: Transformation of the bulk material was analyzed by Scanning Electron Microscopy (SEM), X-ray tomography and Fourier-Transform Infrared spectroscopy (FTIR); releases were quantified by Inductively Coupled Plasma Mass Spectrometry (ICP-MS), single particle-ICP-MS (sp-ICP-MS), Transmission Electron Microscopy (TEM), Analytical Ultracentrifugation (AUC), and UV/Vis spectroscopy. In all scenarios, the detectable particulate releases were attributed primarily to contaminations from handling and machining of the plastics, and were not identified with the pigments, although the contamination of 4 mg/kg (Fe) was dwarfed by the intentional content of 5800 mg/kg (Fe as Fe2O3 pigment). We observed modulations (which were at least partially preventable by UV stabilizers) when comparing as produced and aged nanocomposites, but no significant increase of releases. Release of pigments was negligible within the experimental error for all investigated scenarios, with upper limits of 10 mg/m2 or 1600 particles/mL. This is the first holistic confirmation that pigment nanomaterials remain strongly contained in a plastic that has low diffusion and high persistence such as the polyolefin High Density Polyethylene (HDPE). PMID- 28988477 TI - High-Throughput Low-Background G-Quadruplex Aptamer Chemiluminescence Assay for Ochratoxin A Using a Single Photonic Crystal Microsphere. AB - We reported a novel hemin-G-quadruplex aptamer chemiluminescence assay platform for ochratoxin A (OTA) using the single silica photonic crystal microsphere (SPCM). The oligonucleotide A sequence containing aptamer sequences of hemin and OTA is immobilized on the surface of SPCM. The other oligonucleotide B sequence containing a partially complementary sequence with one part OTA aptamer and one part hemin aptamer is used as a blocking chain. The hybridization between chain A and chain B will be influenced by the presence or absence of OTA in the system, which will affect the bioactivity of DNAzyme. Thus, the chemiluminescence signal depends on the concentration of OTA in the samples. In the single particle assay platform, the signal/noise is remarkably enhanced, and the background signal can be ignored by separating hemin from the surface of SPCM. The limit of detection of the new method reaches to the pg/mL scale, and the linear detection range is 4 orders of magnitude for OTA. The new assay platform can provide a sensitive, cost efficient, simple, and high-throughput screening for OTA. PMID- 28988476 TI - Pinpointing Double Bond and sn-Positions in Glycerophospholipids via Hybrid 193 nm Ultraviolet Photodissociation (UVPD) Mass Spectrometry. AB - Complete structural characterization of complex lipids, such as glycerophospholipids, by tandem mass spectrometry (MS/MS) continues to present a major challenge. Conventional activation methods do not generate fragmentation patterns that permit the simultaneous discernment of isomers which differ in both the positions of acyl chains on the glycerol backbone and the double bonds within the acyl chains. Herein we describe a hybrid collisional activation/UVPD workflow that yields near-complete structural information for glycerophospholipids. This hybrid MS3 strategy affords the lipid's sum composition based on the accurate mass measured for the intact lipid as well as highly specific diagnostic product ions that reveal both the acyl chain assignment (i.e., sn-position) and the site specific location of double bonds in the acyl chains. This approach is demonstrated to differentiate sn-positional and double-bond-positional isomers, such as the regioisomeric phosphatidylcholines PC 16:0/18:1(n-9) and PC 18:1(n 9)/16:0, and has been integrated into an LC-MS3 workflow. PMID- 28988478 TI - Identification of Collagen-Derived Hydroxyproline (Hyp)-Containing Cyclic Dipeptides with High Oral Bioavailability: Efficient Formation of Cyclo(X-Hyp) from X-Hyp-Gly-Type Tripeptides by Heating. AB - Cyclic dipeptides (2,5-diketopiperazines) are present in a variety of foods and are reported to demonstrate antioxidant, antidepressant, and other beneficial effects. We recently developed a novel collagen hydrolysate characterized by a high content of X-hydroxyproline (Hyp)-Gly-type tripeptides using ginger protease. In the present study, we found that, through heating, X-Hyp-Gly can be easily converted into Hyp-containing cyclic dipeptides. After heating for 3 h at 85 degrees C and pH 4.8, Ala-Hyp-Gly was almost completely cyclized to cyclo(Ala Hyp), in contrast to a slight cyclization of Ala-Hyp. The contents of cyclo(Ala Hyp) and cyclo(Leu-Hyp) reached 0.5-1% (w/w) each in the ginger-degraded collagen hydrolysate under the heating conditions. Oral administration experiments using mice revealed that cyclo(Ala-Hyp) and cyclo(Leu-Hyp) were absorbed into the blood at markedly higher efficiencies compared to collagenous oligopeptides, including Pro-Hyp. The high productivity and oral bioavailability of the collagen-specific cyclic dipeptides suggest significant health benefits of the heat-treated ginger degraded collagen hydrolysate. PMID- 28988479 TI - Selective and Sensitive Detection of Methylcytosine by Aerolysin Nanopore under Serum Condition. AB - Detection of DNA methylation in real human serum is of great importance to push the development of clinical research and early diagnosis of human diseases. Herein, taking advantage of stable pore structure of aerolysin in a harsh environment, we distinguish methylated cytosine from cytosine using aerolysin nanopore in human serum. Since wild-type (WT) aerolysin enables high sensitivity detection of DNA, the subtle difference between methylated cytosine and cytosine could be measured directly without any specific designs. Methylated cytosine induced a population of I/I0 = 0.53 while cytosine was focused on I/I0 = 0.56. The dwell time of methylated cytosine (5.3 +/- 0.1 ms) was much longer than that of cytosine (3.9 +/- 0.1 ms), which improves the accuracy for the discrimination of the two oligomers. Moreover, the pore-membrane system could remain stable for more than 2 h and achieve the detection of methylated cytosine with zero background signal in the presence of serum. Additionally, event frequency of methylated cytosine is in correspondence with the relative concentration and facilitate the quantification of methylation. PMID- 28988480 TI - Tunable Photoluminescence across the Visible Spectrum and Photocatalytic Activity of Mixed-Valence Rhenium Oxide Nanoparticles. AB - Materials exhibiting excitation-wavelength-dependent photoluminescence, PL, are useful in a range of biomedical and optoelectronic applications. This paper describes a nanoparticulate material whose PL is tunable across the entire visible range and is achieved without adjusting particle size, any postsynthetic doping, or surface modification. A straightforward thermal decomposition of rhenium (VII) oxide precursor yields nanoparticles that comprise Re atoms at different oxidation states. Studies of time-resolved emission spectra and DFT calculations both indicate that tunable PL of such mixed-valence particles originates from the presence of multiple emissive states that become "active" at different excitation wavelengths. In addition, the nanoparticles exhibit photocatalytic activity that, under visible-light irradiation, is superior to that of TiO2 nanomaterials. PMID- 28988481 TI - Long-Chain Perfluoroalkyl acids (PFAAs) Affect the Bioconcentration and Tissue Distribution of Short-Chain PFAAs in Zebrafish (Danio rerio). AB - Short- and long-chain perfluoroalkyl acids (PFAAs), ubiquitously coexisting in the environment, can be accumulated in organisms by binding with proteins and their binding affinities generally increase with their chain length. Therefore, we hypothesized that long-chain PFAAs will affect the bioconcentration of short chain PFAAs in organisms. To testify this hypothesis, the bioconcentration and tissue distribution of five short-chain PFAAs (linear C-F = 3-6) were investigated in zebrafish in the absence and presence of six long-chain PFAAs (linear C-F = 7-11). The results showed that the concentrations of the short chain PFAAs in zebrafish tissues increased with exposure time until steady states reached in the absence of long-chain PFAAs. However, in the presence of long chain PFAAs, these short-chain PFAAs in tissues increased until peak values reached and then decreased until steady states, and the uptake and elimination rate constants of short-chain PFAAs declined in all tissues and their BCFss decreased by 24-89%. The inhibitive effect of long-chain PFAAs may be attributed to their competition for transporters and binding sites of proteins in zebrafish with short-chain PFAAs. These results suggest that the effect of long-chain PFAAs on the bioconcentration of short-chain PFAAs should be taken into account in assessing the ecological and environmental effects of short-chain PFAAs. PMID- 28988482 TI - Electrocatalytic Radical Dichlorination of Alkenes with Nucleophilic Chlorine Sources. AB - We report a Mn-catalyzed electrochemical dichlorination of alkenes with MgCl2 as the chlorine source. This method provides operationally simple, sustainable, and efficient access to a variety of vicinally dichlorinated compounds. In particular, alkenes with oxidatively labile functional groups, such as alcohols, aldehydes, sulfides, and amines, were transformed into the desired vicinal dichlorides with high chemoselectivity. Mechanistic data are consistent with metal-mediated Cl atom transfer as the predominant pathway enabling dual C-Cl bond formation and contradict an alternative pathway involving electrochemical evolution of chlorine gas followed by Cl2-mediated electrophilic dichlorination. PMID- 28988483 TI - Importance of Nonclassical sigma-Hole Interactions for the Reactivity of lambda3 Iodane Complexes. AB - Key for the observed reactivity of lambda3-iodanes, powerful reagents for the selective transfer of functional groups to nucleophiles, are the properties of the 3-center-4-electron bond involving the iodine atom and the two linearly arranged ligands. This bond is also involved in the formation of the initial complex between the lambda3-iodane and a nucleophile, which can be a solvent molecule or a reactant. The bonding in such complexes can be described by means of sigma-hole interactions. In halogen compounds, sigma-hole interaction was identified as a force in crystal packing or in the formation of supramolecular chains. More recently, sigma-hole interactions were also shown to affect the reactivity of the iodine-based hypervalent reagents. Relative to their monovalent counterparts, where the sigma-hole is located on the extension of the sigma-bond, in the hypervalent species our DFT calculations reveal the formation of a nonclassical sigma-hole region with one or even two maxima. This observation is also made in fully relativistic calculations. The SAPT analysis shows that the sigma-hole bond between the lambda3-iodane and the nucleophile is not necessarily of purely electrostatic nature but may also contain a significant covalent component. This covalent component may facilitate chemical transformation of the compound by means of reductive elimination or other mechanisms and is therefore an indicator for its reactivity. Here, we also show that the shape, location, and strength of the sigma-holes can be tuned by the choice of ligands and measures such as Bronsted activation of the iodane reagent. At the limit, the tuning transforms the nonclassical sigma-hole regions into coordination sites, which allows us to control how a nucleophile will bind and react with the iodane. PMID- 28988484 TI - Flaxseed Oil Alleviates Chronic HFD-Induced Insulin Resistance through Remodeling Lipid Homeostasis in Obese Adipose Tissue. AB - Emerging evidence suggests that higher circulating long-chain n-3 polyunsaturated fatty acids (n-3PUFA) levels were intimately associated with lower prevalence of obesity and insulin resistance. However, the understanding of bioactivity and potential mechanism of alpha-linolenic acid-rich flaxseed oil (ALA-FO) against insulin resistance was still limited. This study evaluated the effect of FO on high-fat diet (HFD)-induced insulin resistance in C57BL/6J mice focused on adipose tissue lipolysis. Mice after HFD feeding for 16 weeks (60% fat-derived calories) exhibited systemic insulin resistance, which was greatly attenuated by medium dose of FO (M-FO), paralleling with differential accumulation of ALA and its n-3 derivatives across serum lipid fractions. Moreover, M-FO was sufficient to effectively block the metabolic activation of adipose tissue macrophages (ATMs), thereby improving adipose tissue insulin signaling. Importantly, suppression of hypoxia-inducible factors HIF-1alpha and HIF-2alpha were involved in FO-mediated modulation of adipose tissue lipolysis, accompanied by specific reconstitution of n-3PUFA within adipose tissue lipid fractions. PMID- 28988485 TI - Purification, Selection, and Partition Coefficient of Highly Oxidized Carbon Dots in Aqueous Two-Phase Systems Based on Polymer-Salt Pairs. AB - In general, the methodologies for the preparation of carbon dots (CDs) lead to the formation of nanostructures with size and surface chemistry heterogeneity. Because the electronic and optical properties of these nanoparticles are directly associated with these properties, the development of purification and selection strategies is essential. Herein, we report a systematic study of the spontaneous partition and separation of highly oxidized carbon dots (OCDs) prepared by the dehydration and oxidation reactions of cotton cellulose in aqueous two-phase systems (ATPSs) based on polymer-salt pairs. The partition of the CDs was investigated in different ATPSs in which the effects of the cations and anions of the salts, molecular mass and nature of the polymer, tie-line length, initial pH, and surface modification of the nanoparticles on the partition coefficient (K) were evaluated. The results showed that the best separation occurred with a system consisting of PEO1500 + lithium sulfate + water using reduced CDs with hydrazine. Alternatively, the lowest value of K, 0.79, was obtained for a poly(ethylene oxide) PEO1500 + sodium tartrate + water system with pH = 6 using OCDs. The detailed analyses of the top and bottom phases of the systems with fluorescence and ultraviolet-visible spectroscopy showed that ATPSs are capable, in addition to partitioning, of separating the nanoparticles with different optical properties, which are directly associated with the surface properties and particle sizes. We believe that the presented methodology is an alternative, practical, fast, and potentially scalable technique for the separation of carbon nanostructures with different optical properties. PMID- 28988486 TI - Photo-CIDNP Reveals Different Protonation Sites Depending on the Primary Step of the Photoinduced Electron-/Proton-Transfer Process with Ru(II) Polyazaaromatic Complexes. AB - The excited-state quenching of [Ru(TAP)2(HAT)]2+ (TAP = 1,4,5,8 tetraazaphenanthrene, HAT= 1,4,5,8,9,12-hexaazatriphenylene) by hydroquinone (H2Q), N-acetyl-tyrosine (N-Ac-Tyr) or guanosine-5'-monophosphate (GMP) was investigated at various pH values. The quenching occurs via electron/proton transfer, as evidenced by transient absorption spectroscopy and confirmed by 1H photochemically induced dynamic nuclear polarization (photo-CIDNP). Reductive quenching also occurs in strongly acidic solution despite a much shorter lifetime of the protonated excited-state complex. Photo-CIDNP revealed a different mechanism at low pH, involving protonation before electron transfer and yielding a distinct protonated monoreduced complex. The experimental photo-CIDNP patterns are consistent with density functional theory calculations. This work highlights the power of 1H photo-CIDNP for characterizing, at the atomic level, transient species involved in electron-transfer processes. PMID- 28988487 TI - Mechanisms and Control of Self-Emulsification upon Freezing and Melting of Dispersed Alkane Drops. AB - Emulsification requires drop breakage and creation of a large interfacial area between immiscible liquid phases. Usually, high-shear or high-pressure emulsification devices that generate heat and increase the emulsion temperature are used to obtain emulsions with micrometer and submicrometer droplets. Recently, we reported a new, efficient procedure of self-emulsification (Tcholakova et al. Nat. Commun. 2017, 8, 15012), which consists of one to several cycles of freezing and melting of predispersed alkane drops in a coarse oil-in water emulsion. Within these freeze-thaw cycles of the dispersed drops, the latter burst spontaneously into hundreds and thousands of smaller droplets without using any mechanical agitation. Here, we clarify the main factors and mechanisms, which drive this self-emulsification process, by exploring systematically the effects of the oil and surfactant types, the cooling rate, and the initial drop size. We show that the typical size of the droplets, generated by this method, is controlled by the size of the structural domains formed in the cooling-freezing stage of the procedure. Depending on the leading mechanism, these could be the diameter of the fibers formed upon drop self-shaping or the size of the crystal domains formed at the moment of drop-freezing. Generally, surfactant tails that are 0-2 carbon atoms longer than the oil molecules are most appropriate to observe efficient self-emulsification. The specific requirements for the realization of different mechanisms are clarified and discussed. The relative efficiencies of the three different mechanisms, as a function of the droplet size and cooling procedure, are compared in controlled experiments to provide guidance for understanding and further optimization and scale-up of this self-emulsification process. PMID- 28988488 TI - Influence of Environmental Factors on the Fate of Legacy and Emerging Per- and Polyfluoroalkyl Substances along the Salinity/Turbidity Gradient of a Macrotidal Estuary. AB - This study aimed at bridging knowledge gaps regarding the land-sea transport of per- and polyfluoroalkyl substances (PFASs) through riverine discharge into coastal waters. The present survey was conducted in the Gironde estuary (southwestern France) where PFASs were ubiquitously detected albeit at low levels. Emerging PFASs such as fluorotelomer sulfonates or polyfluoroalkyl phosphate diesters accounted for a relatively minor proportion of ?PFASs, while perfluorooctanesulfonate, perfluorohexanesulfonate, and perfluorohexanoate were the predominant congeners. Multiple linear regressions provided insights into the relative influence of factors controlling PFAS sediment levels. In that respect, the organic carbon fraction (strongly correlated to sediment grain size) appeared as a more important controlling factor than black carbon or distance from upstream sources for long-chain perfluoroalkyl acids. In the maximum turbidity zone (suspended solids up to 2600 mg L-1), the particle-associated fraction was almost consistently >50% for long-chain perfluoroalkyl carboxylates and sulfonates (>=C8 and >= C6, respectively). Empirical models of KD partitioning coefficients were derived by integrating, for the first time, both particle concentration and salting-out effects. These results represent significant progress toward the development of numerical transport models integrating both PFAS partitioning and 3D-hydrosedimentary dynamics, with a view to estimate PFAS mass budgets at the land-sea interface. PMID- 28988490 TI - The measurement of functioning using the International Classification of Functioning, Disability and Health: comparing qualifier ratings with existing health status instruments. AB - BACKGROUND: The International Classification of Functioning, Disability and Health is the international standard for describing and monitoring functioning. While the categories, the units of the classification, were not designed with measurement in mind, the hierarchical structure of the classification lends itself to the possibility of summating categories into some higher order domain. Focusing on the chapters of d4 Mobility, d5 Self-Care and d6 Domestic Life, this study seeks to ascertain if qualifiers rating of categories (0-No problem to 4 Complete problem) within those chapters can be summated, and whether such derived measurement is consistent with estimates obtained from well-known instruments which purport to measure the same constructs. METHODS: The current study applies secondary analysis to data previously collected in the context of validating Core Sets for stroke, rheumatoid arthritis, and osteoarthritis. Data included qualifier-based ratings of the categories in the Core Sets, and the physical functioning sub-scale of the Short-Form 36, and the World Health Organization Disability Assessment Schedule 2.0. To examine qualifier-comparator scale item agreement Kappa statistics were used. To identify whether appropriate gradients of the comparator scales were observed across qualifier levels, an Independent Sample Median Test of the ordinal scores was deployed. To investigate the internal validity of the summated ICF categories, the Rasch model was applied. RESULTS: Data from 2,927 subjects from Europe, Australasia, Middle East and South America were available for analysis; 36.3% had experienced a stroke, 35.8% osteoarthritis, and 27.9% had rheumatoid arthritis. The items from the Short-Form 36 could not match directly the qualifier categories as the former had only 3 response options. The Kappa between World Health Organization Disability Assessment Schedule 2.0 items and categories was low. For all qualifiers, a significant (<0.001) overall gradient was observed across the comparator scales. Only in few of the World Health Organization Disability Assessment Schedule 2.0 items could no discrete level be detected. The aggregation of the qualifiers at the Chapter and higher order levels mostly revealed fit to the Rasch model. Almost all ICF qualifiers showed ordered thresholds suggesting that the current structure and response options of the qualifiers worked as intended. CONCLUSIONS: The findings of this study provide supporting evidence for the use of the professionally rated categories and associated qualifiers to measure functioning. Implication for Rehabilitation This study provides evidence that functioning data can be collected directly with the International Classification of Functioning, Disability and Health (ICF) by using the ICF categories as items and the ICF qualifiers as rating scale. The findings of this study show the aggregated ratings of ICF categories from the chapters d4 Mobility, d5 Self-care, and d6 Domestic life capture a broader spectrum of the construct than the corresponding summated items from the SF36-Physical Function sub-scale and the corresponding items of the World Health Organization Disability Assessment Schedule 2.0. This study illustrates the potential of building quantitative measurement by aggregating ICF categories and their qualifier ratings into meaningful domains. PMID- 28988491 TI - Left atrial outflow obstruction in double-outlet right atrium. AB - We describe an unusual case of partial atrioventricular septal defect with malalignment of the septum primum to the left atrium with respect to the ventricular septum, committing the tricuspid valve to both ventricles (double outlet right atrium). Abnormal attachment of the septum primum to the lateral aspect of mitral annulus resulted in left atrial outflow obstruction. The patient underwent successful surgical correction. PMID- 28988492 TI - Attending school after treatment for a brain tumor: Experiences of children and key figures. AB - Reintegration into school is a milestone for childhood brain tumor survivors, as well as for their parents, teachers, and healthcare providers. We explored their experiences following the school re-entry by conducting semi-structured interviews. Thematic analysis resulted in four main themes: "school performance," "psychosocial well-being," "support and approach," and "communication and collaboration." Children were pleased to return to school despite confrontation with adverse outcomes. Parents, teachers, and healthcare providers identified current and future concerns and challenges, as well as opportunities for academic and personal development. Their experiences highlight the importance of coordinated and systematic follow-up in close collaboration with healthcare providers. PMID- 28988493 TI - Goal feedback from whom? A physical activity intervention using an N-of-1 RCT. AB - OBJECTIVE: Adolescents are not meeting the recommended guidelines for physical activity. Social support and self-regulatory skills are two factors known to impact physical activity and sedentary behaviour. The study sought to examine how targeting feedback as part of a self-regulatory process could increase physical activity, and the individual who should be providing the feedback. DESIGN: The study utilised an aggregated N-of-1 RCT which allows for an iterative process of intervention development, and examines variability within participants to answer the question for whom did the intervention work. Ten adolescents (ages 13-18) set a daily physical activity goal. Adolescents received a SMS text message providing feedback on goal attainment daily from a parent, peer, behavioural health specialist; or no text message (control). MAIN OUTCOME MEASURES: A bioharness heart rate monitor assessed heart rate as proxy for goal attainment. Adolescents also self-monitored their physical activity in the Calorie Counter and Diet Tracker by MyFitnessPalTM app (commercially available). RESULTS: Intervention demonstrated a significant effect for 30% of the sample in increasing MVPA (Mincrease = 52 min), with no significant effect on sedentary behaviour. CONCLUSION: A single occasion of text messaging from the right person can produce changes, however, careful consideration should be given to who provides the feedback. PMID- 28988489 TI - Fatty infiltration of the minor salivary glands is a selective feature of aging but not Sjogren's syndrome. AB - OBJECTIVE: Determine the presence and assess the extent of fatty infiltration of the minor salivary glands (SG) of primary SS patients (pSS) as compared to those with non-SS sicca (nSS). METHODS: Minor SG biopsy samples from 134 subjects with pSS (n = 72) or nSS (n = 62) were imaged. Total area and fatty replacement area for each glandular cross-section (n = 4-6 cross-sections per subject) were measured using Image J (National Institutes of Health, Bethesda, MD). The observer was blinded to subject classification status. The average area of fatty infiltration calculated per subject was evaluated by logistic regression and general linearized models (GLM) to assess relationships between fatty infiltration and clinical exam results, extent of fibrosis and age. RESULTS: The average area of fatty infiltration for subjects with pSS (median% (range) 4.97 (0.05-30.2)) was not significantly different from that of those with nSS (3.75 (0.087-41.9). Infiltration severity varied widely, and subjects with fatty replacement greater than 6% were equivalently distributed between pSS and nSS participants (chi2 p = .50). Age accounted for all apparent relationships between fatty infiltration and fibrosis or reduced saliva flow. The all-inclusive GLM for prediction of pSS versus non-SS classification including fibrosis, age, fatty replacement, and focus score was not significantly different from any desaturated model. In no iteration of the model did fatty replacement exert a significant effect on the capacity to predict pSS classification. CONCLUSIONS: Fatty infiltration is an age-associated phenomenon and not a selective feature of Sjogren's syndrome. Sicca patients who do not fulfil pSS criteria have similar rates of fatty infiltration of the minor SG. PMID- 28988494 TI - Extravasation of contrast (Spot Sign) predicts in-hospital mortality in ruptured arteriovenous malformation. AB - BACKGROUND AND PURPOSE: The spot sign is a highly specific and sensitive predictor of hematoma expansion in following primary intracerebral hemorrhage (ICH). Rare cases of the spot sign have been documented in patients with intracranial hemorrhage secondary to arteriovenous malformation (AVM). The purpose of this retrospective study is to assess the accuracy of spot sign in predicting clinical outcomes in patients with ruptured AVM. MATERIALS AND METHODS: A retrospective analysis of a prospectively maintained database was performed for patients who presented to West China Hospital with ICH secondary to AVM in the period between January 2009 and September 2016. Two radiologists blinded to the clinical data independently assessed the imaging data, including the presence of spot sign. Statistical analysis using univariate testing, multivariate logistic regression testing, and receiver operating characteristic curve (AUC) analysis was performed. RESULTS: A total of 116 patients were included. Overall, 18.9% (22/116) of subjects had at least 1 spot sign detected by CT angiography, 7% (8/116) died in hospital, and 27% (31/116) of the patients had a poor outcome after 90 days. The spot sign had a sensitivity of 62.5% and specificity of 84.3% for predicting in-hospital mortality (p = .02, AUC 0.734). No correlation detected between the spot sign and 90-day outcomes under multiple logistic regression (p = .19). CONCLUSIONS: The spot sign is an independent predictor for in-hospital mortality. The presence of spot sign did not correlate with the 90 day outcomes in this patient cohort. The results of this report suggest that patients with ruptured AVM with demonstrated the spot sign on imaging must receive aggressive treatment early on due to the high risk of mortality. PMID- 28988495 TI - The beneficial effects of l-cysteine on brain antioxidants of rats affected by sodium valproate. AB - Oxidative stress caused by sodium valproate (SV) is known to play a key role in the pathogenesis of brain tissue. The present study was designed to evaluate the protective effect of l-cysteine (LC) on the antioxidants of brain tissue of rats. The animals were divided into six groups: control group 1 was treated with saline as vehicle, groups 2 and 3 were treated with low and high doses of SV (100 and 500 mg/kg, respectively), group 4 was treated with LC (100 mg/kg), and groups 5 and 6 were treated with low-dose SV + LC and high-dose SV + LC, respectively. All the groups were treated orally by gastric tube for 30 successive days. Some antioxidant parameters were determined. Brain tissue (cerebral cortex) of SV treated animals showed an increase in lipid peroxidation (LPO) and reduction in activity of enzymatic antioxidant and total antioxidant levels. Histopathological examination of cerebral cortex of SV rats showed astrocytic swelling, inflammation, and necrosis. After 4 weeks of the combination treatment of SV and LC daily, results showed significant improvement in the activity of cathepsin marker enzymes and restored the structure of the brain. LC was able to ameliorate oxidative stress deficits observed in SV rats. LC decreased LPO level and was also able to restore the activity of antioxidant enzymes as well as structural deficits observed in the brain of SV animals. The protective effect of LC in SV treated rats is mediated through attenuation of oxidative stress, suggesting a therapeutic role for LC in individuals treated with SV. PMID- 28988496 TI - 6-Gingerol prevents MEHP-induced DNA damage in human umbilical vein endothelia cells. AB - Mono (2-ethylhexyl) phthalate (MEHP) is the principal metabolite of di (2 etylhexyl) phthalate, which is widely used as a plasticizer, especially in medical devices. MEHP has toxic effects on cardiovascular system. The aim of this study was to investigate the possibility that 6-gingerol may inhibit the oxidative DNA damage of MEHP in human umbilical vein endothelial cells (HUVECs) and the potential mechanism. The comet assay was used to monitor DNA strand breaks. We have shown that 6-gingerol significantly reduced the DNA strand breaks caused by MEHP. MEHP increased the levels of reactive oxygen species and malondialdehyde, decreased the level of glutathione and activity of superoxide dismutase, and altered the mitochondrial membrane potential. In addition, DNA damage-associated proteins (p53 and p-Chk2 (T68)) were significantly increased by the treatment of MEHP. Those effects can all be protected by 6-gingerol. The results firmly indicate that 6-gingerol may have a strong protective ability against the DNA damage caused by MEHP in HUVECs, and the mechanism may relate to the antioxidant activity. PMID- 28988497 TI - S-Allyl cysteine alleviates inflammation by modulating the expression of NF kappaB during chromium (VI)-induced hepatotoxicity in rats. AB - Hexavalent chromium (Cr (VI)) is a common environmental pollutant. Cr (VI) exposure can lead to severe damage to the liver, but the preventive measures to diminish Cr (VI)-induced hepatotoxicity need further study. S-allyl cysteine (SAC) is a constituent of garlic ( Allium sativum) and has many beneficial effects to humans and rodents. In this study, we intended to analyze the mechanistic role of SAC during Cr (VI)-induced hepatotoxicity. Male Wistar albino rats were induced with 17 mg/kg body weight to damage the liver. The Cr (VI) induced rats were treated with 100 mg/kg body weight of SAC as an optimum dosage to treat hepatotoxicity. We observed that the levels of oxidants, lipid peroxidation and hydroxyl radical (OH*) were increased, and enzymatic antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase were found to be decreased in Cr (VI)-induced rats. While treated with SAC, the levels of oxidants were decreased and enzymatic antioxidants were significantly ( p < 0.05) increased. Lysosomal enzyme activities were increased in Cr (VI)-induced rats and on treatment with SAC, the activities were significantly decreased. The expressions of nuclear factor-kappa B (p65-NF-kappaB), tumor necrosis factor alpha (TNF-alpha), and inducible nitric oxide synthase (iNOS) were increased during induction with Cr (VI). Subsequent administration of SAC to animals showed a decrease in the expressions of NF kappaB, TNF-alpha, and iNOS. Results obtained from this study clearly demonstrated that SAC protects the liver cells from the Cr (VI)-induced free radical damage. PMID- 28988498 TI - 2-Methyl-4-chlorophenoxyacetic acid (MCPA) and bromoxynil herbicide ingestion. AB - CONTEXT: Ingestion of bromoxynil and 2-methyl-4-chlorophenoxyacetic acid (MCPA) in combination is associated with high mortality. Toxicity is characterised by hyperthermia and metabolic acidosis. Dialysis is a proposed treatment, but little data exist regarding its effectiveness. CASE DETAILS: Case 1: A 50-year-old female presented 18 h post-ingestion of 200 mL of bromoxynil(200 g/L) and MCPA(200 g/L). She was agitated, tachycardic and tachypnoeic. She was intubated and continuous venovenous haemodiafiltration (CVVHDF) was commenced. She deteriorated, becoming hypotensive, hyperthermic (39.5 degrees C) and hypercapnic (80 mmHg). She was cooled, paralysed, received CVVHDF for 2d and was extubated on day 4 making a full recovery. Case 2: A 60-year-old male presented 6 h post-ingestion of an unknown amount of bromoxynil (200 g/L) and MCPA (200 g/L). On arrival, he was tachycardic and tachypneic (pCO2 25 mmHg). At 8h post ingestion he became hyperthermic, hypercapnic and acidotic (pH 7.15), and was intubated, paralysed, cooled and received CVVHDF for 36 h. He was extubated after 42 h and made a full recovery. Bromoxynil and MCPA serum and effluent concentrations were measured. Peak MCPA serum concentrations were 161 ug/ml and 259 ug/ml and peak bromoxynil concentrations were 119 ug/ml and 155 ug/ml in case 1 and 2, respectively. The estimated clearance of both herbicides by CVVHDF was low (<10 mL/min). CONCLUSION: CVVHDF did not result in significant clearance of either herbicide but may have assisted with hyperthermia control. Both patients survived with vigorous cooling, paralysis and ventilatory support. PMID- 28988499 TI - Polymer therapeutics and the EPR effect. AB - History of the EPR (enhanced permeability and retention) effect is discussed, which goes back to the analyses of molecular pathology in bacterial infection and edema (extravasation) formation. The first mediator we found for extravasation was bradykinin. Later on, were found nitric oxide and superoxide, then formation of peroxynitrite, that activates procollagenase. In this inflammatory setting many other vascular mediators are involved that are also common to cancer vasculature. Obviously cancer vasculature is defective architechtally, and this makes macromolecular drugs more permeable through the vascular wall. The importance of this pathophysiological event of EPR effect can be applied to macromolecular drug-delivery, or tumor selective delivery, which takes hours to achieve in the primary as well as metastatic tumors, not to mention of the inflamed tissues. The retention of the EPR means that such drugs will be retained in tumor tissues more than days to weeks. This was demonstrated initially, and most dramatically, using SMANCS, a protein-polymer conjugated-drug dissolved in lipid contrast medium (Lipiodol) by administering intraarterially. For disseminating the EPR concept globally, or in the scientific community, Professor Ruth Duncan played a key role at the early stage, as she worked extensively on polymer- therapeutics, and knew its importance. PMID- 28988500 TI - A safety evaluation of evolocumab. AB - INTRODUCTION: Evolocumab is an injectable, fully human monoclonal antibody and a member of the newest class of low density lipoprotein cholesterol (LDL-C) lowering agents called proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. The PCSK9 inhibitors are the most significant advance in lipid therapy since the introduction of the first statin 30 years ago. Areas covered: The PCSK9 monoclonal antibodies have demonstrated a consistently high LDL-C lowering efficacy with and without statins and/or other lipid lowering therapies (LLT). LDL-C levels achieved with these agents are lower than has ever been possible before. This review will focus on the overall safety of evolocumab including cognitive impairment, very low LDL-C levels, new onset diabetes and glucose abnormalities, effect on vitamin E and steroid hormones, liver and muscle abnormalities, and immunogenicity and injection site reactions. The phase II and III clinical trials had relatively low patient-years of exposure, but the open label extension studies and the recently published outcomes trial, FOURIER, will be the focus of this paper. The safety profile of evolocumab to date is remarkable and extremely encouraging as will be demonstrated. Expert opinion: The PCSK9 inhibitors will be responsible for a new era in lipid therapy that will expand our knowledge of lipid levels and cardiovascular disease (CVD) prevention with an efficacy and safety profile not previously available in clinical practice. PMID- 28988501 TI - Dermatofibrosarcoma protuberans and gastrointestinal stromal tumor as models for targeted therapy in soft tissue sarcomas. AB - INTRODUCTION: The development of novel targeted treatment in soft tissue sarcomas (STS) is important since many sarcoma subtypes are resistant to chemotherapy and effective therapeutic options are limited. Areas covered: This review discusses the molecular background and treatment in two STS types which became a model for targeted therapy - gastrointestinal stromal tumor (GIST) and dermatofibrosarcoma protuberans (DFSP). DFSP is characterized, by chromosomal translocation which results in the formation of COL1A1-PDGFB fusion gene causing platelet-derived growth factor receptor beta(PDGFRB) signaling activation in tumor cells. The majority of GIST malignancies are associated with activating, constitutive, mutually exclusive mutations of two genes: KIT and PDGFRA (PDGF receptor-alpha). Molecular diagnostics are an essential part of GIST and DFSP management. The first effective systemic therapy in clinical practice in GIST and DFSP was imatinib - tyrosine kinase inhibitor acting on KIT and PDGFR alpha/beta. Use of the drug revolutionized treatment of inoperable and/or metastatic cases and demonstrated activity in locally advanced cases. This review summarizes the analogies of therapy and perspectives of GIST and DFSP management. Expert commentary: The next generation of kinase inhibitors are approved for use after the progression of GIST during imatinib treatment. However, little is known about treatment beyond progression in DFSP. PMID- 28988502 TI - Reassessing the species status of Pseudodiaptomus malayalus Wellershaus, 1969 and P. binghami Sewell, 1912 (Calanoida: Pseudodiaptomidae) from India based on morphology and mitochondrial cytochrome oxidase I gene sequences. AB - Pseudodiaptomus binghami Sewell, 1912 was first described from the Rangoon River (now Yangon River) estuary, Myanmar. Pseudodiaptomus malayalus Wellershaus, 1969 previously known as P. binghami malayalus, is a typical brackish-water calanoid copepod from Cochin Estuary, Kerala. Morphological examination of P. malayalus and P. binghami collected from Cochin Estuary and the Nambur canal in Andhra Pradesh revealed crucial differences between the two congeners. Female specimens of P. malayalus exhibited marked differences from those described by Wellershaus. They are (1) the number of terminal spines on P5, (2) ornamentation of GS, (3) ornamentation of Ur1-4, (4) length ratio of the Ur and CR segments and (5) length:width ratio of the CR setae. Furthermore, significant and discrete morphological differences were observed between the two Indian species in their P5 and urosome. But the male specimens of P. malayalus did not show any major differences from the original description. In addition, distance matrix data revealed 22% interspecific divergence values which in turn confirmed the status of P. malayalus and P. binghami as two distinct species. PMID- 28988503 TI - The misleading choice for safer births in Brazilian's most developed region: a cross-sectional study. AB - PURPOSE: To analyze the Cesarean Section (CS) rate in Brazilian women according to category of health insurance and individual characteristics associated with the mode of delivery. MATERIALS AND METHODS: A cross-sectional study was performed in three maternity services (one public tertiary referral center, one maternity service for both public and private care, and one private maternity service) in Campinas city, Brazil. Eligibility criteria were: inpatient during the immediate postpartum period, hospital birth, single pregnancy, and live newborn. Sociodemographic and anthropometric data, reproductive history, pregnancy planning, and prenatal care information was obtained from participants. Comorbidities, type of birth, and newborn data were collected from medical records. The mode of delivery was categorized as either CS or vaginal delivery. RESULTS: A total of 1276 women were included in this study. The overall CS rate was 57.5%. CS rates were 41.6, 54.8, and 90.1% for public, mixed (public and private), and private maternity services, respectively. Mean age was higher in women who had a CS (28.0 +/- 6.0 years versus 25.9 +/- 6.5 years, p < .0001) as was the mean Body Mass Index (25.2 +/- 5.3 kg/m2 versus 23.8 +/- 4.5 kg/m2, p < .0001). CS was related to higher education, employment, white skin color, planned pregnancy, antenatal care in a private service, and primiparity. CONCLUSIONS: The overall CS rate was high (greater than 50%); in the private service, almost all participants had a CS delivery (90.1%). Better socioeconomic conditions and primiparity were associated with higher CS rates in Brazil. Political pressure for the management of unnecessary CSs is vital in Brazil. Together with the provision of real incentives for normal deliveries in public and, most importantly, private services. PMID- 28988504 TI - Low colonic absorption drugs: risks and opportunities in the development of oral extended release products. AB - INTRODUCTION: Currently numerous drugs have been observed with lower colonic absorption than small intestine absorption, which can significantly impact in vivo performance of their oral extended release (ER) products. Areas covered: We reviewed over 300 publications, patents, book chapters, and commercial reports of drug products from regulatory agencies for low colonic absorption (LCA) drugs and critical findings are discussed. The focuses of this article are (1) current findings on the causes of low colonic absorption to support early assessment of LCA candidates, and (2) current knowledge on successful ER strategies and technical platforms used for LCA drugs in commercial drug products to facilitate oral ER product development. Expert opinion: Colonic drug absorption is one of the critical considerations in successful development of oral ER products. The root causes of low colonic absorption in many LCA drugs are still unclear. It is recommended to evaluate colonic drug absorption of drug candidate at early stage of oral ER product development. After evaluation, the selection of a formulation platform to develop an oral ER product needs to be carefully considered for LCA drugs. Based on the current commercial oral ER formulation platforms for LCA drugs, compounds are first divided into five types (I-V) and different ER formulation approaches with higher success rate are recommended for each type. PMID- 28988505 TI - Clinical and pharmacokinetic drug evaluation of delafloxacin for the treatment of acute bacterial skin and skin structure infections. AB - INTRODUCTION: In the era of multi-drug resistant pathogens, the adequate treatment of skin and skin structure infections remains a challenge for clinicians. Delafloxacin, with its broad spectrum against Gram-positive, Gram negative and anaerobic organisms, represents a new therapeutic option in this setting, especially when coverage of methicillin-resistant Staphylococcus aureus is required in the empirical or targeted approach. Areas covered: In this drug evaluation, the Authors have reviewed the pharmacokinetic and pharmacodynamic characteristics of delafloxacin. In addition, recent data on clinical efficacy and safety from clinical trials have been included. Expert opinion: Delafloxacin represents an attractive therapeutic option due to a broad antimicrobial and favorable pharmacokinetic and pharmacodynamic profile. Several in vitro studies have demonstrated the low potential for resistance selection if used in empirical regimens. Delafloxacin is a promising candidate for the treatment of Gram positive infections, especially if co-infection with other pathogens is suspected. This is because of the very low MIC of the agent for Gram-positive (including MRSA) and anaerobic bacteria and because of the wide spectrum of activity against Gram-negative organisms. For these interesting microbiological and PK/PD characteristics we expect future uses of this drug in other indications such as diabetic foot infection, osteomyelitis, prosthetic joint infections, abdominal infections and central nervous system infections. PMID- 28988506 TI - In silico ADME-Tox modeling: progress and prospects. AB - INTRODUCTION: Although significant progress has been made in high-throughput screening of absorption, distribution, metabolism and excretion, and toxicity (ADME-Tox) properties in drug discovery and development, in silico ADME-Tox prediction continues to play an important role in facilitating the appropriate selection of candidate drugs by pharmaceutical companies prior to expensive clinical trials. Areas covered: This review provides an overview of the available in silico models that have been used to predict the ADME-Tox properties of compounds. It also provides a comprehensive overview and summarization of the latest modeling methods and algorithms available for the prediction of physicochemical characteristics, ADME properties, and drug toxicity issues. Expert opinion: The in silico models currently available have greatly contributed to the knowledge of screening approaches in the early stages of drug discovery and the development process. As the definitive goal of in silico molding is to predict the pharmacokinetics and disposition of compounds in vivo by assembling all kinetic processes within one global model, PBPK models can serve this purpose. However, much work remains to be done in this area to generate more data and input parameters to build more reliable and accurate prediction models. PMID- 28988507 TI - Electromagnetic fields in neonatal incubators: the reasons for an alert. AB - BACKGROUND: Neonatal incubators are important tools for sick newborns in the first few days of life. Nevertheless, their electric engine, often very close to the newborn's body, emits electromagnetic fields (EMF) to which newborns are exposed. Aim of this paper is to review the available literature on EMF exposure in incubators, and the effects of such exposures on newborns that have been investigated. METHODS: We carried out a systematic review of studies about EMF emissions produced by incubators, using Medline and Embase databases from 1993 to 2017. RESULTS: We retrieved 15 papers that described the EMF exposure in incubators and their biological effects on babies. EMF levels in incubators appear to be between 2 and 100 mG, depending on the distance of the mattress from the electric engine. In some cases, they exceed this range. These values interfere with melatonin production or with vagal tone. Even caregivers are exposed to high EMF, above 200 mG, when working at close contact with the incubators. CONCLUSION: EMF have been described as potentially hazardous for human health, and values reported in this review are an alert to prevent babies' and caregivers' exposure when close to the incubators. A precautionary approach should be adopted in future incubator design, to prevent high exposures of newborns in incubators and of caregivers as well. PMID- 28988508 TI - Immunological effects of everolimus in patients with metastatic renal cell cancer. AB - The mammalian target of rapamycin (mTOR) is a crucial kinase present in all cells. Besides its role in the regulation of cell-growth, proliferation, angiogenesis, and survival of malignant tumors, mTOR additionally plays an important role in immune regulation by controlling the balance between effector T cells and regulatory T cells (Tregs). This critically affects the suppressive state of the immune system. Here, the systemic immunological effects of everolimus treatment were comprehensively investigated in five patients with metastatic renal cell cancer. In this hypothesis generating study, the immunological alterations in circulating immune subsets induced by everolimus included a (non-significant) increase in the frequency of Tregs, a significant increase in monocytic myeloid-derived suppressor cells, a significant decrease in the frequency of immunoregulatory natural killer cells, classical CD141+ (cDC1) and CD1c+ (cDC2) dendritic cell subsets, as well as a decrease in the activation status of plasmacytoid dendritic cells and cDC1. These date indicate that the immunological effects of everolimus affect multiple immune cell subsets and altogether tip the balance in favor of immunosuppression, which can be considered a detrimental effect in the treatment of cancer, and may require combination treatment with agents able to negate immune suppression and boost T cell immunity. PMID- 28988509 TI - Darunavir for use in pregnant women with HIV. AB - INTRODUCTION: Combination antiretroviral therapy is recommended during pregnancy to decrease the rate of HIV transmission to the baby and reduce morbidity in the mother. More than 50% of women are prescribed a protease inhibitor-based regimen during pregnancy. Darunavir was recently reclassified as a first-line protease inhibitor for use in pregnancy in the US Department of Health and Human Services Perinatal Guidelines. Areas covered: This is a brief review of the use of protease inhibitor therapy during pregnancy, and a discussion of darunavir's utility in this area. Clinical pharmacology and trial data are reviewed, and the safety, efficacy and dosing of darunavir during pregnancy is discussed. Expert commentary: Darunavir has become an important option in the management of HIV during pregnancy. Both once-daily dosing and twice-daily dosing regimens have shown efficacy in clinical studies. Although a significant reduction in total (protein bound and unbound) plasma concentrations of darunavir has been noted during pregnancy, antiviral activity appears to be maintained with standard dosing. This is likely due to diminished changes in unbound drug concentrations. Preterm delivery and low birth weight have been noted for pregnancies of women on darunavir-containg regimens, but a causal relationship has not yet been demonstrated. PMID- 28988510 TI - Tyrosine kinase inhibitors rechallenge in solid tumors: a review of literature and a case description with lenvatinib in thyroid cancer. AB - INTRODUCTION: In the last decade tyrosine kinase inhibitors (TKIs) have been employed for a wide range of hematological and solid tumors and today they represent a valid therapeutic option for different neoplasms. Among them, both sorafenib and lenvatinib were approved for the treatment of radioactive iodine (RAI) refractory differentiated thyroid carcinoma (DTC). Unfortunately, in some cases the efficacy of TKIs is limited by the onset of drug resistance after the initial response. Areas covered: We report the case of a patient with a RAI refractory advanced DTC, treated with lenvatinib after surgery, multiple RAI administrations, traditional chemotherapy, and sorafenib. During treatment with lenvatinib, a noticeable response was detected by sequential computed tomography scans but, after 27 months, tumor progression became evident and led to lenvatinib interruption. In absence of any active treatment, a further disease progression was documented, and lenvatinib was re-administered obtaining a new objective response. Starting from this case report, we review available reports about the rechallenge with TKIs in solid tumors, discussing the possible mechanisms underlying the efficacy of this approach. Expert commentary: Rechallenge with TKIs in solid tumors could be a therapeutic option in subjects with advanced and metastatic DTC who experience a progressive disease after initial response to lenvatinib. PMID- 28988511 TI - Adaptation for participation! AB - PURPOSE: To explore children's experiences with testing, acquiring and using assistive devices. METHODS: Nine children (six boys, three girls, 9-12 years old, with different physical disability and activity experience, participated in semistructured interviews. The interviews were audio-taped, transcribed and analysed using Systematic text condensation. RESULTS: Assistive devices were reported to contribute to cope activities that the children otherwise would not have participated in. Several subjects listed the need for a shielded environment when adapting to new equipment. The children highlighted "independence in activities" and "having the opportunity to participate in activities with family and friends" as important for frequent use. Need for assistance and lack of localizations to perform the activities were listed as reasons for less frequent use. CONCLUSIONS: This study reveals that it is useful to map each child's opportunities for independency, appropriate locations for performing the activity and participation with friends, when considering obtaining assistive devices. Implications for Rehabilitation The use of assistive devices gives many children with physical disabilities the opportunity to participate in physical activity. Improving availability to assistive devices for physical activity should be a priority to help facilitate participation. Having opportunities to develop perceptions of competence may be essential for a child's long term participation in physical activity. PMID- 28988513 TI - Step-to-step spatiotemporal variables and ground reaction forces of intra individual fastest sprinting in a single session. AB - We aimed to investigate the step-to-step spatiotemporal variables and ground reaction forces during the acceleration phase for characterising intra-individual fastest sprinting within a single session. Step-to-step spatiotemporal variables and ground reaction forces produced by 15 male athletes were measured over a 50-m distance during repeated (three to five) 60-m sprints using a long force platform system. Differences in measured variables between the fastest and slowest trials were examined at each step until the 22nd step using a magnitude-based inferences approach. There were possibly-most likely higher running speed and step frequency (2nd to 22nd steps) and shorter support time (all steps) in the fastest trial than in the slowest trial. Moreover, for the fastest trial there were likely-very likely greater mean propulsive force during the initial four steps and possibly very likely larger mean net anterior-posterior force until the 17th step. The current results demonstrate that better sprinting performance within a single session is probably achieved by 1) a high step frequency (except the initial step) with short support time at all steps, 2) exerting a greater mean propulsive force during initial acceleration, and 3) producing a greater mean net anterior posterior force during initial and middle acceleration. PMID- 28988512 TI - Consistency of traumatic brain injury reporting in older adults with and without cognitive impairment. AB - OBJECTIVE: Medical history information regarding prior traumatic brain injury (TBI) usually relies on self-report, although little is known about the reliability of this information with regard to injuries sustained years or decades earlier. Even less is known about the reliability of self-reported medical history information in older individuals with cognitive impairment. To this end, we assessed the test-retest reliability of self-reported TBI history in a large, national sample. METHODS: Participants (n = 4309) were older adults with intact cognition, mild cognitive impairment (MCI) and Alzheimer's disease (AD) from the National Alzheimer's Coordinating Center. Subjects provided TBI history information at baseline and one annual follow-up visit. Consistency of self reported history of TBI with <5 minutes loss of consciousness (mLOC) and TBI with >=5 mLOC reported at time 1 and 2 was analyzed across diagnostic groups. RESULTS: Overall, subjects provided reports of TBI history at follow-up that were highly consistent with baseline reports (97.8-99.6% agreement), and Cohen's kappa coefficients were all larger than .80 and statistically significant, maximum p < .001. Furthermore, level of cognitive impairment was not a significant predictor of consistency in reporting. CONCLUSIONS: These data are some of the first to suggest that self-report may be a consistent method of obtaining remote TBI history in the absence of medical records for older individuals, regardless of cognitive impairment. PMID- 28988514 TI - Long-term effects of acoustic reafference training (ART). AB - In sport visual feedback is often used to enhance performance, mostly neglecting the auditory modality. However, athletes produce natural sounds when they move (acoustic reafferences) which they perceive and use to control their movements. We examined the short- and long-term effects of a training intervention on a complex movement by using acoustic reafferences. Natural step sounds produced during hurdling were recorded and played back to the participants immediately before each trial, with an increase (fast group), decrease (slow group), or no manipulation (control group) in the tempo. All groups increased their hurdling performance regarding overall running time, with the slow group showing the best performance development. After a 10-week retention, the fast and slow group further increased performance, whereas the control group declined. The repeated experience with acoustic information associated with the rhythmic pattern of hurdling may have helped developing a cognitive representation of that movement, especially regarding long-term effects. PMID- 28988515 TI - Pacing profiles of senior men and women at the 2017 IAAF World Cross Country Championships. AB - The purpose of this study was to analyse and compare pacing profiles of senior men and women competing in the 2017 World Cross Country Championships. Finishing and split times were collated for 118 men and 81 women competing over the newly introduced race distance of 10 km (five laps of approximately 2 km). Athletes were grouped according to finishing time, and changes in pace measured using lap times, except between Laps 1 and 2 because of a shorter first lap (times relative to the winner were used instead). Within both men's and women's races, groups slowed during the early stages, but then either sped up or maintained pace during the last lap. There were few differences between groups with regard to overall pacing profiles, or between sexes. The men's fast finish contrasted with slower finishes found in previous editions (over 12 km), and the degree to which women were slower than men (approximately 12%) was very similar to track racing and showed the decision to equalise the distances run by both sexes was sound. As in other distance events, athletes are recommended to try to achieve an even pace throughout, an approach that proved beneficial to both gold medallists. PMID- 28988516 TI - Quinine and carbenoxolone enhance the anticonvulsant activity of some classical antiepileptic drugs. AB - Objective Quinine (QUIN) and carbenoxolone (CNX) elicit anticonvulsant effects typically characterized by the reduction of the epileptiform activity as well as changes in behavioral parameters related to seizures. Therefore, the aim of this study was to analyze the effects of these molecules on the anticonvulsant activity of some classical antiepileptic drugs. Methods Male Wistar rats were used. Valproate (VPA), phenytoin (PHT), or carbamazepine (CBZ) was administered at sub-therapeutic doses for intraperitoneal via. Subsequently, animals were administered with a single dose of QUIN or CNX. The anticonvulsant activity was evaluated with the maximal electroshock (MES) test and pentylenetetrazole (PTZ) administration. Additionally, the plasma levels of CBZ were determined using an HPLC method. Results All the control rats presented generalized tonic-clonic seizures after the MES test or the administration of PTZ. For the MES test, all of the antiepileptic drugs increased their anticonvulsant activity when were co administered with QUIN. For the PTZ test, only the combination CBZ plus QUIN significantly increased the percentage of protection against the generalized tonic-clonic seizures. The co-administration of CBZ plus QUIN resulted in an augmented concentration of CBZ in plasma. Discussion The present study shows that QUIN and CNX enhance the anticonvulsant activity of some classical antiepileptic drugs. However, only the combination CBZ/QUIN had significant effects on both MES and PTZ models. Such anticonvulsant activity could be attributed to increased levels of CBZ in plasma. We propose that these molecules could improve the pharmacological actions of antiepileptic drugs administered at sub-therapeutic doses. PMID- 28988517 TI - Developing and testing a consensus-based core set of outcome measures for rehabilitation in musculoskeletal diseases. AB - OBJECTIVES: Rehabilitation is important for people with musculoskeletal diseases (MSDs), and evaluating the effect of rehabilitation on both an individual and group level is advocated. A consensus concerning use of outcome measures will improve collaboration between healthcare providers, and increase the possibility of conducting meta-analyses in future research. The aim of this study was to develop a consensus-based core set of outcome measures for rehabilitation in MSDs, and to test the feasibility and responsiveness of the set. METHOD: The core set was developed through a stepwise process comprising a Delphi consensus procedure, systematic literature searches, and a pilot study, including 386 patients, to test the feasibility and responsiveness of the set. RESULTS: The following aspects and outcome measures were selected: pain [numeric rating scale (NRS)], fatigue (NRS), physical fitness (the 30-second Sit to Stand test), mental health (Hopkins Symptom Checklist 5), daily activities (Hannover Functional Questionnaire), goal attainment (Patient-Specific Functional Scale including motivation score for baseline assessment), quality of life (5-level EuroQol 5 Dimensions), social participation (the social participation item from COOP/WONCA) and coping (Effective Musculoskeletal Consumer Scale-17). All tested outcome measures were found to be feasible, with high completion rates and acceptable score distribution. Standard response means varied from 0.3 to 0.9. CONCLUSIONS: A consensus-based core set of patient reported outcome measures is presented for evaluating rehabilitation in MSDs. The core set is feasible and responsive for use in Norway, but needs further testing in other countries. PMID- 28988518 TI - RhBMP-2-loaded Poly(lactic-co-glycolic acid) microspheres fabricated by coaxial electrospraying for protein delivery. AB - In this study, we fabricated recombinant human bone morphogenetic protein-2 (rhBMP-2) loaded Poly(lactic-co-glycolic acid) (PLGA) microspheres with core shell structures and particle sizes ranging from 2.5 to 8 MUm by coaxial electrospraying. The manufacturing process of core-shell microspheres by coaxial electrospraying is simpler than that with other methods, and a smaller diameter can be obtained. The microspheres were analyzed by environmental scanning electron microscopy, transmission electron microscopy (TEM), and laser scanning confocal microscopy (LSCM). Moreover, the drug release profiles and degradation of rhBMP-2-loaded PLGA microspheres in vitro were investigated for 21 days and for 7 weeks, respectively. The rhBMP-2 was stabilized by using bovine serum albumin (BSA) to ensure protein activity in the electrospraying process. Fluorescently labeled protein that was loaded into the core-shell PLGA microspheres was verified by LSCM. The distinct layered structure that existed in the manufactured core-shell microspheres can be observed by TEM. Cell Counting Kit-8 (CCK-8) indicated that the core-shell PLGA microspheres loaded with rhBMP-2 have great potential for the treatment of bone defects, for bone regeneration, and in bone tissue engineering. PMID- 28988519 TI - Effect of unilateral nephrectomy on urinary angiotensinogen levels in living kidney donors: 1 year follow-up study. AB - BACKGROUND: Urinary angiotensinogen (uAGT) has recently been proposed as a marker of kidney injury and activated intrarenal renin-angiotensin system. We investigated the effects of living donor nephrectomy on uAGT levels, blood pressure, estimated glomerular filtration rate, proteinuria and compensatory hypertrophy in the remaining kidney of living kidney donors. METHODS: Twenty living kidney donors were included in the study and followed for 1 year. uAGT levels were measured with enzyme-linked immunosorbent assay preoperatively and postoperatively at the 15th day, 1, 6 and 12 months. RESULTS: Four donors were excluded from the study due to lack of data. The mean baseline estimated glomerular filtration rate was 98 +/- 15 ml/min/1.73 m2. Serum creatinine, uAGT/creatinine, uAGT/protein levels were higher and estimated glomerular filtration rate was lower than baseline values at all time periods. Urinary protein/creatinine levels increased after donor nephrectomy, but after 6 months they returned to baseline values. Renal volume increased after nephrectomy, but these changes did not show any correlation with uAGT/creatinine, uAGT/protein, estimated glomerular filtration rate or systolic/diastolic blood pressures. uAGT/creatinine at 6 months and urinary protein/creatinine ratio at 12 months showed a positive correlation ( P=0.008, r=0.639). CONCLUSION: After donor nephrectomy, increasing uAGT levels can be the result of activation of the intrarenal renin-angiotensin system affecting the compensatory changes in the remaining kidney. The long-term effects of increased uAGT levels on the remaining kidney should be examined more closely in future studies. PMID- 28988520 TI - A comparison of the effect of short-acting and long-acting cloxacillin-based dry cow therapy on somatic cell counts after calving in cows also given internal teat sealants. AB - AIM: To compare, in cows treated with an internal teat sealant, the effect of short-acting and long-acting cloxacillin-based dry-cow therapy on somatic cell counts (SCC) after calving. METHODS: Cows from a spring-calving, pasture-based dairy farm in the Manawatu-Whanganui region of New Zealand were randomly allocated to receive either a short-acting cloxacillin and ampicillin dry-cow therapy and internal teat sealant (n=291) or a long-acting cloxacillin and ampicillin dry-cow therapy and internal teat sealant (n=288) at the end of lactation. Cows were managed on-farm with routine husbandry procedures through the dry period and following calving. A multivariable logistic regression model was used to determine the association between length of action of dry-cow therapy and the proportion of cows with a SCC >150,000 cells/mL at the first herd test after calving. RESULTS: Age of cow, mean SCC for the preceding season and interval from calving to the first post-calving herd test were all associated with the proportion of cows with an individual SCC >150,000 cells/mL at the first herd test (p<0.001) Treatment with the short-acting dry-cow therapy was not associated with decreased odds of cows having a SCC >150,000 cells/mL at the first herd test compared with treatment with long-acting dry-cow therapy (OR=0.724; 95% CI=0.40-1.30). CONCLUSIONS AND CLINICAL RELEVANCE: In this herd, which routinely used internal teat sealants, the use of short-acting cloxacillin based dry-cow therapy did not result in an increased proportion of cows with elevated SSC post-calving. This was a single farm, single year study but indicates that in this herd, changing from a long-acting to a short-acting antimicrobial may have no impact on the prevalence of subclinical mastitis. PMID- 28988521 TI - The cardioprotective effect of rosmarinic acid on acute myocardial infarction and genes involved in Ca2+ homeostasis. AB - Acute myocardial infarction (AMI) is a common cause of hospitalisation and high mortality due to lethal arrhythmias. Sarcoplasmic reticulum Ca2+ ATPase (SERCA2) and ryanodine receptor (RyR2) regulate the cytosolic Ca2+ ion concentration. Rosmarinic acid (RA) is one of the most common caffeic esters in Rosmarinus officinalis. The present study was conducted to test the hypothesis whether RA can protect cardiac function against AMI and arrhythmias induced by isoproterenol through the regulatory effect of SERCA2 and RyR2 gene expression. To this aim, male Sprague-Dawley rats were allocated into in vivo and ex vivo studies and received RA (10, 15, and 30 mg/kg; 14 days). AMI was induced by two consecutive subcutaneous injections of 100 mg/kg isoproterenol. Blood pressure (BP), heart rate, electrocardiography (ECG) parameters, plasma levels of cardiac biomarkers, and antioxidative enzymes were evaluated (in vivo study). Cardiac functions were measured in isolated hearts using Langendorff set up. Gene expressions of SERCA2 and RyR2 were measured in left ventricular heart. Isoproterenol administration showed a significant decline in BP, QRS voltage, activities of antioxidant enzymes, cardiac function, and gene expressions of SERCA2 and RyR2. The results also indicated a significant increase in heart rate, ST-elevation, cardiac biomarkers, and antioxidant enzymes. RA at 30 mg/kg dosage showed the best effect on the improvement of the mentioned factors. This study suggests that RA has potent cardioprotective effects against AMI and arrhythmia, which may be due to its ability to enhance expression of plasma antioxidant enzymes and genes involved in Ca2+ homeostasis SERCA2 and RyR2. The protective role of RA is also possibly related to its antiadrenergic effects. PMID- 28988522 TI - Intellectual performance of kidney transplant recipients' offspring: a cross sectional, multicenter study. AB - OBJECTIVE: The number of successful pregnancies in kidney transplant (KT) recipients has increased in recent years. Little evidence is available about the risk of in utero immunosuppressive exposure for long-term cognitive consequences. The aim of this study was to evaluate the impact of immunosuppression during pregnancy on intellectual performance of children born to KT recipients. METHODS: Using a cross-sectional design, women who had undergone KT and their children (aged 4+ years) were recruited at the outpatient follow-up in five transplant centers. Women who did not receive immunosuppression during pregnancy with similar distributions of socioeconomic status and length of gestation and their children were also recruited. Children were assessed with Wechsler Intelligence Scales. RESULTS: The study sample included 50 exposed and 50 unexposed children. No differences between groups in all the proposed confounding factors were found. Full-scale IQ did not differ significantly between both groups. Also, significant differences in any index or subscale score were not observed, with the exception of time required to complete the Wechsler preschool and primary scale of intelligence (WPPSI) Zoo locations subtest, which was done quicker in the unexposed group (p = .007). Exposure to immunosuppression during pregnancy was not a significant predictor of low IQ in logistic regression after adjustment for other factors. CONCLUSIONS: Immunosuppression therapy during pregnancy of KT women did not affect global intellectual performance of their offspring, except maybe for visuospatial working memory in preschool children. PMID- 28988523 TI - Immunopathology in drug resistant mesial temporal lobe epilepsy with different types of hippocampal sclerosis. AB - PURPOSE: There is evidence that autoimmunity has a specific role in temporal lobe seizures of limbic encephalitis patients. Our aim in this study was to investigate any histopathological clues of autoimmune process in refractory temporal lobe epilepsy (TLE) patients with different pathologically proven hippocampal sclerosis (HS) types. METHODS: 22 patients who had undergone epilepsy surgery due to mesial TLE-HS were included. The sera of patients are tested for neuronal antibodies to N-methyl-D-aspartate receptors (NMDAR), leucine-rich, glioma inactivated 1 (LGI1), contactin-associated protein 2 (CASPR2), alpha-amino 3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), gamma-aminobutyric acid B receptor (GABABR) and glutamic acid decarboxylase (GAD). Pathological and immunohistochemical investigations including neuronal nuclei (NeuN), NMDAR, GAD, glial fibrillary acidic protein (GFAP), CD8+-CD3+ lymphocytes and immunoglobulin G (IgG) were done. Patients were grouped according to type of HS. Clinical features and immunohistochemical changes were defined in these groups. RESULTS: Available sera of 15 patients did not have any neuronal antibodies. Thirteen of 22 patients had HS type 1, three had HS type 2 and two had HS type 3. According to immunohistochemical investigations CD3+ and CD8+ T cell infiltration was more prominent in the hippocampus of patients with classical HS (International League Against Epilepsy (ILAE) Type 1 HS) and there was a significant negative correlation between epilepsy duration and numbers of CD3+-CD8+ lymphocytes in temporal lobe parenchyma. CONCLUSION: The role of T cell-mediated immunopathology and immunopathological difference in a variety of drug resistant TLE-H2S patients was suggested. These findings can be helpful in understanding the epileptogenicity of HS. PMID- 28988524 TI - Safety of hormonal contraception for obese women. AB - INTRODUCTION: Obese women have special safety requirements for contraceptive choice, but the evidence supporting such decision is dispersed and sometimes conflicting. Despite being effective, well tolerated and safe for most women, hormonal contraceptives are underused by obese women due to fear of contraceptive failure, weight gain and venous thrombosis. Areas covered: We performed a comprehensive literature search to identify studies about hormonal contraception in overweight and obese women, including safety concerns. We considered the safety of hormonal contraceptives for otherwise healthy obese women and for those with comorbidities such as hypertension, diabetes, vascular disease, or a history of deep venous thrombosis. Expert opinion: Over time there is no convincing evidence that obesity increases the risk of contraceptive failure. Hormonal contraceptive users may have a modest weight gain that is comparable to that of non-users. Current evidence supports the safe use of combined hormonal contraceptives by obese women after detailed clinical screening to exclude comorbidities that may contraindicate the use of estrogens. Progestin-only methods are generally safe, and long-acting reversible contraceptives hold the best combination of efficacy, safety and convenience for this group, although individualization is advisable. PMID- 28988525 TI - The role of biofilm forming on mortality in patients with candidemia: a study derived from real world data. AB - BACKGROUND: Evaluation of the role on patient mortality exerted by biofilm forming (BF) Candida strains, by using predictive clinical data. METHODS: Eighty nine strains isolated from Candida bloodstream infection, occurring in two Italian University Hospitals, were employed in this study. A random forest (RF) model was built with a procedure of iterative selection of the risk factors potentially able to predict the probability of death. The similarity between patient conditions and Bayesian clustering was calculated in order to evaluate the role of predictors in the stratification of the death risk. RESULTS: Three different groups of patients with different probability of death were obtained with a RF approach: Group 1 (mortality in 33.3% of cases), Group 2 (death in 50% of cases), and Group 3 (mortality in 76.9% of cases). The comparison between these three groups showed that BF correlated well with increased mortality in patients, admitted for medical diagnosis, with high APACHE II score and treated with azoles. Early treatment within 24 h between candidemia diagnosis and the beginning of antifungal therapy was associated with the lowest of BF rate and mortality. CONCLUSIONS: BF by Candida spp. seems to be clinically associated with increased mortality especially in medical patients with higher Apache II score or treated with azoles. PMID- 28988526 TI - Wound healing properties of PVA/starch/chitosan hydrogel membranes with nano Zinc oxide as antibacterial wound dressing material. AB - In this work, hydrogel membranes were developed based on poly vinyl alcohol (PVA), starch (St), and chitosan (Cs) hydrogels with nano Zinc oxide (nZnO). PVA/St/Cs/nZnO hydrogel membranes were prepared by freezing-thawing cycles, and the aqueous PVA/St solutions were prepared by dissolving PVA in distilled water. After the dissolution of PVA, starch was mixed, and the mixture was stirred. Then, chitosan powder was added into acetic acid, and the mixture was stirred to form a chitosan solution. Subsequently, Cs, St and PVA solutions were blended together to form a homogeneous PVA/St/Cs ternary blend solution. Measurement of Equilibrium Swelling Ratio (ESR), Water Vapor Transmission Test (WVTR), mechanical properties, scanning electron microscopy (SEM), MTT [3-(4, 5 dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide] assay, antibacterial studies, in vivo wound healing effect and histopathology of the hydrogel membranes were then performed. The examination revealed that the hydrogel membranes were more effective as a wound dressing in the early stages of wound healing and that the gel could be used in topic applications requiring a large spectrum of antibacterial activity; namely, as a bandage for wound dressing. PMID- 28988528 TI - Klotho Protein: Its Role in Aging and Central Nervous System Pathology. AB - This review is devoted to Klotho protein and recent evidences for its functions in the brain. Information on transcriptional regulation of the klotho gene and posttranslational modifications of the protein resulting in multiple forms of Klotho is reviewed. Evidence is summarized that Klotho regulates the activity of protein factors, enzymes, and receptors, including data suggesting the importance of its glycosidase activity. Effects of Klotho on components of the glutamatergic neurotransmitter system, signal cascades involving protein kinases and protein phosphorylation, as well as oligodendrocyte differentiation and myelination are discussed. A possible contribution is proposed for Klotho levels in the development of central nervous system pathologies including mental disorders. PMID- 28988527 TI - How Fucose of Blood Group Glycotopes Programs Human Gut Microbiota. AB - Formation of appropriate gut microbiota is essential for human health. The first two years of life is the critical period for this process. Selection of mutualistic microorganisms of the intestinal microbiota is controlled by the FUT2 and FUT3 genes that encode fucosyltransferases, enzymes responsible for the synthesis of fucosylated glycan structures of mucins and milk oligosaccharides. In this review, the mechanisms of the selection and maintenance of intestinal microorganisms that involve fucosylated oligosaccharides of breast milk and mucins of the newborn's intestine are described. Possible reasons for the use of fucose, and not sialic acid, as the major biological signal for the selection are also discussed. PMID- 28988529 TI - Effect of Anesthetics on Efficiency of Remote Ischemic Preconditioning. AB - Remote ischemic preconditioning of hind limbs (RIPC) is an effective method for preventing brain injury resulting from ischemia. However, in numerous studies RIPC has been used on the background of administered anesthetics, which also could exhibit neuroprotective properties. Therefore, investigation of the signaling pathways triggered by RIPC and the effect of anesthetics is important. In this study, we explored the effect of anesthetics (chloral hydrate and Zoletil) on the ability of RIPC to protect the brain from injury caused by ischemia and reperfusion. We found that RIPC without anesthesia resulted in statistically significant decrease in neurological deficit 24 h after ischemia, but did not affect the volume of brain injury. Administration of chloral hydrate or Zoletil one day prior to brain ischemia produced a preconditioning effect by their own, decreasing the degree of neurological deficit and lowering the volume of infarct with the use of Zoletil. The protective effects observed after RIPC with chloral hydrate or Zoletil were similar to those observed when only the respective anesthetic was used. RIPC was accompanied by significant increase in the level of brain proteins associated with the induction of ischemic tolerance such as pGSK-3beta, BDNF, and HSP70. However, Zoletil did not affect the level of these proteins 24 h after injection, and chloral hydrate caused increase of only pGSK-3beta. We conclude that RIPC, chloral hydrate, and Zoletil produce a significant neuroprotective effect, but the simultaneous use of anesthetics with RIPC does not enhance the degree of neuroprotection. PMID- 28988531 TI - Effect of Light Intensity under Different Photoperiods on Expression Level of Carbonic Anhydrase Genes of the alpha- and beta-Families in Arabidopsis thaliana Leaves. AB - Changes in expression levels of genes encoding carbonic anhydrases alpha-CA1, alpha-CA2, alpha-CA4, beta-CA1, beta-CA2, beta-CA3, beta-CA4, beta-CA5, and beta CA6 in Arabidopsis thaliana leaves after light increase from 80 to 400 umol PAR quanta.m-2.s-1 were investigated under short day (8 h) and long day (16 h) photoperiods. The expression of two forms of the gene, At3g01500.2 and At3g01500.3, encoding the most abundant carbonic anhydrase of leaves, beta-CA1, situated in chloroplast stroma, was found. The content of At3g01500.3 transcripts was higher by approximately an order of magnitude compared to the content of At3g01500.2 transcripts. When plants were adapted to high light intensity under short day photoperiod, the expression level of both forms increased, whereas under long day photoperiod, the content of At3g01500.3 transcripts increased, and the content of transcripts of At3g01500.2 decreased. The expression levels of the At3g01500.3 gene and of genes encoding chloroplast carbonic anhydrases alpha-CA1, alpha-CA4, alpha-CA2 and cytoplasmic carbonic anhydrase beta-CA2 increased significantly in response to increase in light intensity under short day, and these of the first three genes increased under long day as well. The expression level of the gene encoding alpha-CA2 under long day photoperiod as well as of genes of chloroplast beta-CA5 and beta-CA4 from plasma membranes and mitochondrial beta-CA6 under both photoperiods depended insignificantly on light intensity. Hypotheses about the roles in higher plant metabolism of the studied carbonic anhydrases are discussed considering the effects of light intensity on expression levels of the correspondent genes. PMID- 28988530 TI - Hyperexpression of Integrin alpha5beta1 Promotes Resistance of MCF-7 Human Breast Carcinoma Cells to Doxorubicin via ERK Protein Kinase Down-regulation. AB - In MCF-7 human breast carcinoma cells, alpha5beta1 integrin hyperexpression, which was accomplished by transduction of a full-length alpha5 integrin cDNA, increased by about 50-70% the number of cells, survived during 48-72 h cell treatment with doxorubicin. Up-regulation of alpha5beta1 reduced the level of the apoptogenic p53 protein and p21 cell cycle inhibitor, but enhanced the activity of Akt and mTOR protein kinases. In addition to these findings, we observed a significant decrease in the activity of both isoforms of phosphokinase Erk1/2, which is known to play a key role in cell viability pathways, including pathways alleviating stress damages caused by distinct antitumor drugs. Diminished Erk activity accompanying the rise of drug resistance can be explained by an "atypical" function of this kinase, which, in the cells studied, promotes an enhanced rather than reduced sensitivity to doxorubicin. To verify this suggestion, the effect of a specific Erk inhibitor, PD98059, on the resistance to doxorubicin of control and alpha5 cDNA-transduced MCF-7 cells was investigated. The data showed that suppression of Erk activity increased the resistance of control cells (transduced with an "empty" vector) to a level higher than that demonstrated by the alpha5 cDNA-transduced cells. The highest level of resistance was observed in alpha5beta1-trancduced cells treated with PD98059. Akt and mTOR kinase inhibitors had little if any effect on doxorubicin resistance of alpha5 cDNA-transduced MCF-7 cells. The data show for the first time that integrin alpha5beta1 can stimulate drug resistance of tumor cells through a mechanism based on the inhibition of protein kinase Erk. From a more general view, the results of this investigation suggest that signal protein kinases can perform in tumor cells "non-canonical" functions, opposite to those, which are the basis for using kinase inhibitors in targeted cancer therapy. It follows that if a protein kinase is supposed to be used as a target for such therapy, it is important to explore its features in the particular tumor prior to the onset of treatment. PMID- 28988532 TI - Interaction of Cholera Toxin B-subunit with Human T-lymphocytes. AB - In this work, 125I-labeled cholera toxin B-subunit (CT-B) (specific activity 98 Ci/mmol) was prepared, and its high-affinity binding to human blood T-lymphocytes (Kd = 3.3 nM) was determined. The binding of the 125I-labeled CT-B was inhibited by unlabeled interferon-alpha2 (IFN-alpha2), thymosin-alpha1 (TM-alpha1), and by the synthetic peptide LKEKK, which corresponds to sequences 16-20 of human TM alpha1 and 131-135 of IFN-alpha2 (Ki 0.8, 1.2, and 1.6 nM, respectively), but was not inhibited by the unlabeled synthetic peptide KKEKL with inverted sequence (Ki > 1 uM). In the concentration range of 10-1000 nM, both CT-B and peptide LKEKK dose-dependently increased the activity of soluble guanylate cyclase (sGC) but did not affect the activity of membrane-bound guanylate cyclase. The KKEKL peptide tested in parallel did not affect sGC activity. Thus, the CT-B and peptide LKEKK binding to a common receptor on the surface of T-lymphocytes leads to an increase in sGC activity. PMID- 28988533 TI - Quantitative Affinity Interaction of Ubiquitinated and Non-ubiquitinated Proteins with Proteasome Subunit Rpn10. AB - Recent proteomic profiling of mouse brain preparations using the ubiquitin receptor, Rpn10 proteasome subunit, as an affinity ligand revealed a representative group of proteins bound to this sorbent (Medvedev, A. E., et al. (2017) Biochemistry (Moscow), 82, 330-339). In the present study, we investigated interaction of the Rpn10 subunit of proteasomes with some of these identified proteins: glyceraldehyde-3-phosphate dehydrogenase (GAPDH), pyruvate kinase, and histones H2A and H2B. The study revealed: (i) quantitative affinity interaction of the proteasome subunit immobilized on a Biacore-3000 optical biosensor cuvette with both the GAPDH (Kd = 2.4.10-6 M) and pyruvate kinase (Kd = 2.8.10-5 M); (ii) quantitative high-affinity interaction of immobilized histones H2A and H2B with the Rpn10 subunit (Kd values of 6.5.10-8 and 3.2.10-9 M, respectively). Mass spectrometric analysis revealed the presence of the ubiquitin signature (GG) only in a highly purified preparation of GAPDH. We suggest that binding (especially high-affinity binding) of non-ubiquitinated proteins to the Rpn10 proteasome subunit can both regulate the functioning of this proteasomal ubiquitin receptor (by competing with ubiquitinated substrates) and promote activation of other pathways for proteolytic degradation of proteins destined to the proteasome. PMID- 28988534 TI - Biochemical Variations in Cytolytic Activity of Ortho- and Paramyxoviruses in Human Lung Tumor Cell Culture. AB - Human lung cancer cells (Calu-3 line) were studied for the development of apoptosis, necrosis, and autophagy in response to infection with ortho- and paramyxoviruses. Biochemical pathways underlying various mechanisms of cell death differed for different viruses. When infected with murine Sendai paramyxovirus, Calu-3 cells demonstrated typical necrotic features such as cell swelling (but not shrinkage), lack of chromatin DNA laddering, of caspase 3 and 8 activation, and of apoptotic cleavage of poly(ADP-ribose) polymerase (PARP) protein; an activation of antiapoptotic protein kinase Akt was also revealed. In contrast, infection with avian influenza virus A/FPV/Rostock/34 (H7N1 subtype) or Newcastle disease virus (NDV, avian paramyxovirus) caused the development of typical apoptotic markers such as cell shrinkage, ladder-type chromosomal DNA fragmentation, caspase 3 and 8 activation, and proteolytic cleavage of PARP in the absence of Akt activation. Notably, no upregulation of p53 protein phosphorylation was observed in all infected cells, which indicates that p53 is not involved in the virus-induced death of Calu-3 cells. Cell death caused by the influenza virus was accompanied by overstimulation of autophagy, whereas no stimulation of autophagy was observed in the NDV-infected cells. Infection with Sendai virus caused moderate stimulation of autophagy, which suggests that the mechanism of the virus-induced cell death and the balance between autophagy and cell death in infected cancer cells depend on the virus type and might significantly differ even for closely related viruses. Therefore, an optimal strategy for oncolytic virus-mediated destruction of tumor cells in cancer patients requires selection of the most appropriate oncolytic virus based on the mechanism of its cytolytic action in a particular type of tumor. PMID- 28988535 TI - Reason for Indispensability of Threonine in Humans and Other Mammals in Comparative Aspect. AB - The essential amino acid threonine is not synthesized in vertebrates, so it must be obtained from food. During evolution, the decomposition of threonine has changed. Because the decomposition of threonine catalyzed by threonine dehydratase is irreversible, in the present work attention is focused on threonine dehydrogenase to show the inability of this enzyme to synthesize threonine in a reaction that would be the reverse of the reaction of threonine decomposition. The reason why threonine dehydrogenase cannot be used for the biosynthesis of threonine in mammalian tissues is discussed. It is concluded that some quantity of threonine is involved in transamination. PMID- 28988536 TI - Role of PKA and PI3K in Leptin and Ghrelin Regulation of Adaptive Subpopulations of Regulatory CD4+ T-Lymphocyte Formation. AB - The role of phosphatidylinositol-3 kinase (PI3K) and protein kinase A (PKA) in leptin and ghrelin regulation of formation of adaptive (a) subpopulations of CD4+ T-lymphocytes (helper (h) cells producing interleukin-17A) (aT?17) and of T regulatory lymphocytes (aTreg) in the context of physiological pregnancy is established. It is shown that leptin at a concentration typical for the second half of pregnancy (trimesters II-III) enhances the differentiation of aT?17 with a high level of interleukin-17A (IL-17A) production and the expression of the chemokine receptor CCR6 with the participation of PI3K. Simultaneously, leptin reduces formation of aTreg expressing the suppressor molecule CTLA-4, which determines the function of these cells. Ghrelin at a concentration characteristic of the first half of pregnancy (trimesters I-II), in contrast, enhances aTreg formation and, in parallel, reduces the level aT?17 (that express CCR6) and the IL-17A production by aTh17. PKA, likewise PI3K, participates in regulatory effects of ghrelin on the formation of aT?17 and aTreg. The combined action of leptin and ghrelin (via PKA participation) enhances formation of only aTreg, which determines the priority of this molecular mechanism and explains why the investigated hormones with reciprocal differentiating potential do not come into antagonism at the level of immune system cells during pregnancy. PMID- 28988537 TI - Comparison of Interaction between Ceruloplasmin and Lactoferrin/Transferrin: to Bind or Not to Bind. AB - The year 2016 marked the 50th anniversary of the discovery by S. Osaki who first showed that ceruloplasmin (CP, ferro:O2-oxidoreductase or ferroxidase) is capable of oxidizing Fe(II) to Fe(III) and favors the incorporation of the latter into transferrin (TF). However, much debate remains in the literature concerning the existence of a complex between the enzyme oxidizing iron and the protein facilitating its transport in plasma. We studied CP in exocrine fluids and demonstrated its high-affinity interaction with transferrin found in breast milk and in lacrimal fluid, i.e. with lactoferrin (LF). Here we present data obtained by comparing the interaction of CP with LF and TF using surface plasmon resonance and Hummel-Dreyer chromatography. Binding of apo-LF within the range of concentrations 1.6-51.3 uM with CP immobilized on a CM5-chip is characterized by KD = 1.07 uM. Under similar conditions, the KD for apo-TF was measured and appeared to be higher than 51.3 uM. Hummel-Dreyer chromatography of CP with 51 uM apo-LF/apo-TF in the effluent demonstrated the absence of interaction between apo TF and CP in solution, contrary to efficient interaction between apo-LF and CP. In contrast to LF, the interaction of apo-TF with CP is probably not stable within the physiological range of concentrations of TF. PMID- 28988539 TI - Prevalence and determinants of active trachoma among preschool-aged children in Dembia District, Northwest Ethiopia. AB - BACKGROUND: Trachoma is an infectious eye disease caused by Chlamydia trachomatis, which is the leading infectious cause of blindness worldwide. In areas where trachoma is endemic, active trachoma is common among preschool-aged children, with varying magnitude. This study aimed to estimate the prevalence of active trachoma and associated risk factors among preschool-aged children in Dembia District, northwest Ethiopia. METHODS: A community-based cross-sectional survey was conducted among preschool-aged children of northwest Ethiopia. Multistage systematic random sampling was used to select 695 subjects. Trained clinical optometrists subjected each child to an ocular examination and assessed the presence of active trachoma. Face to face interview using pretested and structured questionnaire were conducted to collect data on possible risk factors. Trachoma cases were graded following a World Health Organization simplified grading scheme. All statistical analysis was carried out using the SPSS software version 20. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were used to identify factors associated with active trachoma. RESULTS: Of the 681 preschool-aged children studied, 18% (95% CI: 15.4% - 21.1%) had a prevalence of active trachoma. Children who had clean faces (absence of nasal and ocular discharges) had a lower chance of having active trachoma [aOR = 0.55, 95% CI: 0.37 - 0.82]. The odds of having active trachoma decreased with an increase in the distance to a water point [aOR = 0.51, 95% CI: 0.33 - 0.78]. Similarly, no or poor utilization of liquid waste disposal in the child's household was associated with an increased chance of having active trachoma [aOR = 3.83, 95% CI: 1.26 - 11.61]. CONCLUSION: The prevalence of active trachoma in these preschool-aged children was found to be high and needs special interventions that focus on educating families about proper face washing, liquid waste disposal, and improving safe water supply near the households. PMID- 28988538 TI - High prevalence of soil-transmitted helminth infections among primary school children, Uttar Pradesh, India, 2015. AB - BACKGROUND: Soil-transmitted helminth (STH) infections often affect the poorest and most deprived communities. In order to generate reliable data for planning a school based deworming program, we conducted a survey among primary school children studying in government schools in the Indian state of Uttar Pradesh. The objectives of our survey were to estimate the prevalence and intensity of STH infections. METHODS: We conducted a cross-sectional survey among children studying in 130 primary schools from 9 agro-climatic zones, during May - August 2015. Information about socio-demographic details, defecation and hand-hygiene practices, and stool samples were collected from the school children. Stool samples were examined using the Kato-Katz method. RESULTS: Stool samples from 6421 school children were examined. The overall weighted prevalence of any STH in the State was 75.6% (95% CI: 71.2-79.5). The prevalence was more than 50% in six of the nine agro-climatic zones. A. lumbricoides was the most prevalent STH (prevalence: 69.6%), followed by hookworm (prevalence: 22.6%) and T. trichura (4.6%). The majority of the STH infections were of low intensity. The practice of open defecation and not washing hands with soap after defecation and residence in kutcha house were significant risk factors of STH infection. CONCLUSIONS: STH prevalence among primary school children in Uttar Pradesh was high. Given the WHO guidelines on deworming frequency according to STH prevalence, Govt of Uttar Pradesh needs to implement a school-based deworming program with bi-annual frequency. The findings of our survey would also help monitor the performance of school based deworming programme. PMID- 28988540 TI - The burden of and risk factors for active trachoma in the North and South Wollo Zones of Amhara Region, Ethiopia: a cross-sectional study. AB - BACKGROUND: Trachoma is a disease of the eye, caused by the bacteria Chlamydia trachomatis, which can lead to blindness if left untreated. Ethiopia is one of the most trachoma-affected countries in the world. The objective of this study was to determine the prevalence of and associated risk factors for active trachoma among children in selected woredas of North and South Wollo Zones in Amhara Region, Ethiopia. METHODS: This study was a community-based, cross sectional study, which was conducted from October to December 2014 among children aged 1-8. A four-stage random cluster sampling technique was employed to select the study areas and participants. From each selected household, one child was clinically assessed for active trachoma. A structured questionnaire was used to collect sociodemographic, behavioral, and clinical data. Multivariate logistic regression analysis was used to analyze the association between predictor variables and active trachoma. RESULTS: The overall prevalence of active trachoma among 1358 children was found to be 21.6% (95% CI: 19.4-23.8%). When analyzed by the presence or absence of individual WHO simplified system signs of active trachoma, trachomatous inflammation-follicular cases constituted18% (95% CI: 15.9 20.2%), while 4.7% (95% CI: 3.6-5.8%) were trachomatous inflammation-intense cases. Ocular discharge (aOR = 5.2; 95% CI: 3.3-8.2), nasal discharge (aOR = 1.8; 95% CI: 1.2-2.7), time taken to fetch water (aOR = 0.02; 95% CI: 0.01-0.05), frequency of hand and face washing (aOR = 4.4; 95% CI: 1.1-17.8), and access to a latrine (aOR = 0.006; 95% CI: 0.001-0.030) were found to be independently associated with the presence of active trachoma. CONCLUSIONS: There is a high burden of active trachoma among children in the study areas. Lack of personal hygiene and limited access to a safe water supply and latrines were associated with increased prevalence of active trachoma. In order to reduce the burden of active trachoma, facial cleanliness and environmental improvement components of the SAFE strategy should be upgraded in the study areas. PMID- 28988543 TI - Sociodemographic, anthropometric and behavioural risk factors for ultra-processed food consumption in a sample of 2-9-year-olds in Brazil. AB - OBJECTIVE: The present study aimed to identify food patterns among 2-9-year-olds and investigate sociodemographic, anthropometric and behavioural predictors of less healthy dietary patterns. DESIGN: Cross-sectional study. Parents of 2-9-year olds completed an FFQ and factor analysis was applied to identify dietary patterns. Parents also completed questionnaires assessing sociodemographic, anthropometric and behavioural characteristics of parents and children, including parental feeding practices. SETTING: Participants were recruited from private schools of Campinas and Sao Paulo, SP, Brazil, between April and June 2014. SUBJECTS: Parents of 2-9-year-olds (n 929). RESULTS: Two dietary patterns emerged: 'traditional food' and 'ultra-processed food'. Lower maternal education (OR=2.05, P=0.010) and higher maternal weight status (OR=1.43, P=0.044) were associated with a greater likelihood of the ultra-processed food pattern. Lower perceived parental responsibility for adequacy of food group intake (OR=2.41, P=0.020), and lower scores on the parental feeding practices of 'Healthy Eating Guidance' (OR=1.83, P<0.001) and 'Monitoring' (OR=2.52, P<0.001), were also associated with the presence of this pattern, as was higher child's screen use during mealtimes (OR=1.61, P=0.004). CONCLUSIONS: The present study is the first to evaluate associations between less healthy dietary patterns of Brazilian 2-9 year-olds and parental feeding practices. Our findings highlight sociodemographic, anthropometric and behavioural factors within families that could be used to target tailored policies to at-risk populations. PMID- 28988542 TI - Children's everyday exposure to food marketing: an objective analysis using wearable cameras. AB - BACKGROUND: Over the past three decades the global prevalence of childhood overweight and obesity has increased by 47%. Marketing of energy-dense nutrient poor foods and beverages contributes to this worldwide increase. Previous research on food marketing to children largely uses self-report, reporting by parents, or third-party observation of children's environments, with the focus mostly on single settings and/or media. This paper reports on innovative research, Kids'Cam, in which children wore cameras to examine the frequency and nature of everyday exposure to food marketing across multiple media and settings. METHODS: Kids'Cam was a cross-sectional study of 168 children (mean age 12.6 years, SD = 0.5) in Wellington, New Zealand. Each child wore a wearable camera on four consecutive days, capturing images automatically every seven seconds. Images were manually coded as either recommended (core) or not recommended (non-core) to be marketed to children by setting, marketing medium, and product category. Images in convenience stores and supermarkets were excluded as marketing examples were considered too numerous to count. RESULTS: On average, children were exposed to non-core food marketing 27.3 times a day (95% CI 24.8, 30.1) across all settings. This was more than twice their average exposure to core food marketing (12.3 per day, 95% CI 8.7, 17.4). Most non-core exposures occurred at home (33%), in public spaces (30%) and at school (19%). Food packaging was the predominant marketing medium (74% and 64% for core and non-core foods) followed by signs (21% and 28% for core and non-core). Sugary drinks, fast food, confectionary and snack foods were the most commonly encountered non-core foods marketed. Rates were calculated using Poisson regression. CONCLUSIONS: Children in this study were frequently exposed, across multiple settings, to marketing of non-core foods not recommended to be marketed to children. The study provides further evidence of the need for urgent action to reduce children's exposure to marketing of unhealthy foods, and suggests the settings and media in which to act. Such action is necessary if the Commission on Ending Childhood Obesity's vision is to be achieved. PMID- 28988544 TI - Molecular and clinical characterization of human respiratory syncytial virus in South Korea between 2009 and 2014. AB - Respiratory syncytial virus (RSV) can cause serious respiratory infections, second only to influenza virus. In order to know RSV's genetic changes we examined 4028 respiratory specimens from local hospital outpatients in Gyeonggi Province, South Korea over six consecutive years by real-time one-step RT-PCR; 183 patients were positive for RSV infection. To investigate the specific distribution of RSV genotypes, we performed partial sequencing of the glycoprotein gene. Of the 131 RSV-A specimens sequenced, 61 (43.3%) belonged to the ON1 genotype, 66 (46.8%) were NA1 genotype, 3 (2.1%) were GA5 genotype, and 1 (0.7%) belonged to the GA1 genotype. Of the 31 RSV-B specimens sequenced, 29 were BA9 genotype (87.9%) and 2 were BA10 genotype (6.1%). The most common clinical symptoms were fever, cough, nasal discharge, and phlegm; multiple logistic regression analysis showed that RSV-positive infection on pediatric patients was strongly associated with cough (OR = 2.8, 95% CI 1.6-5.1) and wheezing (OR = 2.8, 95% CI 1.7-4.4). The ON1 genotype was significantly associated with phlegm (OR = 11.8, 95% CI 3.8-46.7), while the NA1 genotype was associated with the pediatric patients' gender (males, OR = 2.4, 95% CI 1.1-5.4) and presence of chills (OR = 5.1, 95% CI 1.1-27.2). RSV subgroup B was showed association with nasal obstruction (OR = 4.6, 95% CI 1.2-20.0). The majority of respiratory virus coinfections with RSV were human rhinovirus (47.2%). This study contributes to our understanding of the molecular epidemiological characteristics of RSV, which promotes the potential for improving RSV vaccines. PMID- 28988541 TI - A randomised, double-blind clinical phase II trial of the efficacy, safety, tolerability and pharmacokinetics of a single dose combination treatment with artefenomel and piperaquine in adults and children with uncomplicated Plasmodium falciparum malaria. AB - BACKGROUND: The clinical development of a single encounter treatment for uncomplicated malaria has the potential to significantly improve the effectiveness of antimalarials. Exploratory data suggested that the combination of artefenomel and piperaquine phosphate (PQP) has the potential to achieve satisfactory cure rates as a single dose therapy. The primary objective of the study was to determine whether a single dose of artefenomel (800 mg) plus PQP in ascending doses is an efficacious treatment for uncomplicated Plasmodium falciparum malaria in the 'target' population of children <= 5 years of age in Africa as well as Asian patients of all ages. METHODS: Patients in six African countries and in Vietnam were randomised to treatment with follow-up for 42-63 days. Efficacy, tolerability, safety and pharmacokinetics were assessed. Additional key objectives were to characterise the exposure-response relationship for polymerase chain reaction (PCR)-adjusted adequate clinical and parasitological response at day 28 post-dose (ACPR28) and to further investigate Kelch13 mutations. Patients in Africa (n = 355) and Vietnam (n = 82) were included, with 85% of the total population being children < 5 years of age. RESULTS: ACPR28 in the per protocol population (95% confidence interval) was 70.8% (61.13-79.19), 68.4% (59.13-76.66) and 78.6% (70.09-85.67) for doses of 800 mg artefenomel with 640 mg, 960 mg and 1440 mg of PQP respectively. ACPR28 was lower in Vietnamese than in African patients (66.2%; 54.55-76.62 and 74.5%; 68.81 79.68) respectively. Within the African population, efficacy was lowest in the youngest age group of >= 0.5 to <= 2 years, 52.7% (38.80-66.35). Initial parasite clearance was twice as long in Vietnam than in Africa. Within Vietnam, the frequency of the Kelch13 mutation was 70.1% and was clearly associated with parasite clearance half-life (PCt1/2). The most significant tolerability finding was vomiting (28.8%). CONCLUSIONS: In this first clinical trial evaluating a single encounter antimalarial therapy, none of the treatment arms reached the target efficacy of > 95% PCR-adjusted ACPR at day 28. Achieving very high efficacy following single dose treatment is challenging, since > 95% of the population must have sufficient concentrations to achieve cure across a range of parasite sensitivities and baseline parasitaemia levels. While challenging, the development of tools suitable for deployment as single encounter curative treatments for adults and children in Africa and to support elimination strategies remains a key development goal. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02083380 . Registered on 7 March 2014. PMID- 28988545 TI - A controlled trial of screening, brief intervention and referral for treatment (SBIRT) implementation in primary care in the United Arab Emirates. AB - : Aim This project evaluated the effectiveness of screening brief intervention and referral for treatment (SBIRT) in primary care in Abu Dhabi to manage patients with problematic substance use. This study aimed to determine whether: (i) training primary care physicians on the SBIRT model increased the identification of patients using substances at a harmful, hazardous or dependent level; (ii) training improved physicians' knowledge, attitudes and beliefs in self-efficacy in managing substance use. BACKGROUND: Substance use is increasing in the United Arab Emirates yet there has been no formal primary care intervention. SBIRT was considered an appropriate model given its endorsement by the WHO. METHODS: A controlled trial (two intervention and two matched control clinics) was undertaken. Intervention physicians (n=17) were trained in SBIRT. Physicians' attitudes were measured before and after training and eight months after implementation. Target recruitment was 900 patients. Inclusion criteria were: consenting UAE national, ?18 years, using the 'walk-in' primary care clinic. Patient data was collected by physician-administered questionnaire. Prevalence of drug use was measured through electronic patient records. Findings A total of 906 patients were screened, aged 18-82 years and 496 (55%) were female. Of these, 5.7% reported use of amphetamine, 3.9% alcohol, 3.3%, sedatives, 1.7% opioids and 1.1% cannabis. In all, 21 people had a moderate/high ASSIST score and received a brief intervention, but did not attend follow-up; three high-risk people were referred for specialist treatment. Physicians' attitudes towards patients with problematic substance use and providing treatment improved after training, but returned to pre-training levels after eight months. Including the 21 individuals identified from intervention screening, the prevalence of substance use increased to 0.208% (95% CI 0.154-0.274), significantly higher than in control clinics (P<0.001). In conclusion, physicians were generally positive towards SBIRT and SBIRT increased recorded drug related conditions at a practice level. However, poor patient attendance at follow-up requires investigation. PMID- 28988547 TI - Systematic review of the efficacy of non-pharmacological interventions in people with Lewy body dementia. AB - : ABSTRACTBackground:Pharmacological interventions for Lewy body dementia (LBD), especially for its non-cognitive symptoms, are limited in their efficacy and tolerability. Clinicians are often uncertain about non-pharmacological interventions and their efficacy in managing cognitive and non-cognitive symptoms of LBD. Therefore, we aimed to systematically review the existing literature on non-pharmacological interventions for people with LBD. METHODS: We carried out a systematic search using six databases. All human studies examining impact of any non-pharmacological intervention on LBD were assessed for cognitive, physical, psychiatric, and quality-of-life outcomes. Study quality was assessed by Effective Public Health Practice Project Quality Assessment Tool for Quantitative Studies and the CARE criteria checklist. RESULTS: Prevailing evidence supporting the efficacy of non-pharmacological interventions is weak. We screened 1,647 papers. Fifteen studies (n = 61) including 11 case reports were found eligible for this systematic review. Interventions and reported outcomes were heterogeneous. Deep brain stimulation of the nucleus basalis of Meynert reportedly conferred cognitive benefit. Electroconvulsive therapy and repetitive transcranial magnetic stimulation have been reported to ameliorate depressive symptoms. Transcranial direct current stimulation was observed to improve attention. Exercise-based interventions reportedly improve various clinically important outcomes. Spaced retrieval memory training and environmental intervention for "mirror sign" have also been reported. CONCLUSIONS: Several non pharmacological interventions have been studied in LBD. Although evidence supporting their efficacy is not robust, prevailing preliminary evidence and limitations of available pharmacological interventions indicate the need to consider appropriate non-pharmacological interventions, while planning comprehensive care of LBD patients. Larger trials evaluating the efficacy of non pharmacological interventions for LBD are needed. PMID- 28988546 TI - The Impact of Health Anxiety in Multiple Sclerosis: A Replication and Treatment Case Series. AB - BACKGROUND: Multiple sclerosis (MS) is commonly associated with psychological complications. Previous research by Hayter and colleagues (2016) found that in patients with MS, health anxiety (HA) can account for part of the variance in quality of life (QoL) independent of physical and cognitive impairment caused by the disease. MS patients with HA perceived their intact physical and cognitive performance as impaired relative to those without HA and attributed the impairment to MS. These misperceptions might be useful targets in the treatment of HA in MS using cognitive behaviour therapy (CBT). AIMS: Study 1 sought to replicate the main findings from Hayter et al. (2016). Study 2 examined the impact of HA-focused CBT in a case series. METHOD: In Study 1, twenty participants with MS were screened for HA and assigned to either a high or low HA group. They completed assessments of cognitive and physical functioning before rating their performance on these tasks, followed by measures of QoL, mood and physical disability. Four participants in the high HA group subsequently received six sessions of CBT using a consecutive AB case series in Study 2. RESULTS: Study 1 replicated the main findings from the earlier study. In Study 2, three of the four patients who received treatment showed substantial improvements in HA and mood and all showed improvement in QoL. CONCLUSION: Given the high rates of HA in MS patients and its impact on QoL, this case series suggests that a brief CBT intervention could significantly improve patients' wellbeing. PMID- 28988548 TI - The impact of intergenerational programs on children and older adults: a review. AB - : ABSTRACTBackground:Elderly are at particular risk of social isolation. This condition significantly affects health; on the contrary, social involvement can be extremely advantageous. In this context, intergenerational programs improve interactions between different ages. Then, we conducted a review regarding intergenerational programs, to summarize the effects of these activities on both elderly and children. METHODS: Our review followed the PRISMA statements. We considered papers reporting data about intergenerational programs involving children (preschool and elementary) and elderly. RESULTS: The final selection obtained 27 sources. Ten studies evaluated children's outcomes outlining the positive impact of intergenerational programs upon children's perception of elderly. The effects on older participants were variegated considering well being, depression, self-reported health, and self-esteem. Moreover, the retrieved studies outlined the importance of a careful organization and of a specific training for all staff members. The staff involved in similar programs appeared, overall, highly satisfied. DISCUSSION: The positive impact on children of intergenerational programs is proved at both short- and long-term. Moreover, despite the different outcomes considered and the variable results, these programs resulted overall beneficial on elderly participants. Finally, similar activities resulted feasible even in case of older adults with dementia. PMID- 28988549 TI - Low-Intensity Cognitive Behavioural Therapy-Based Music Group (CBT-Music) for the Treatment of Symptoms of Anxiety and Depression: A Feasibility Study. AB - BACKGROUND: Music has the potential to be an effective and engaging therapeutic intervention in the treatment of mental illness. This research area remains underdeveloped. AIMS: This paper reports the feasibility of an innovative low intensity CBT-based music (CBT-Music) group targeted to symptoms of depression and anxiety. METHOD: A total of 28 participants with symptoms of depression and anxiety who were attending community mental health services were recruited for the study and randomized into TAU (treatment as usual) plus low-intensity CBT Music (treatment) or to TAU alone (control). The treatment group consisted of a 9 week music group that incorporated various components of CBT material into a musical context. Feasibility was the primary outcome. The secondary outcomes were a reduction in depression, anxiety (Hospital Anxiety and Depression Scale) and disability (WHO Disability Assessment Schedule 2.0) assessed at baseline and 10 weeks. RESULTS: Recruitment proved feasible, retention rates were high, and the participants reported a high level of acceptability. A randomized control study design was successfully implemented as there were no significant differences between treatment and control groups at baseline. Participants in the treatment group showed improvement in disability (p = 0.027). Despite a reduction in depression and anxiety scores, these differences were not statistically significant. CONCLUSIONS: A low-intensity CBT-based music group can be successfully administered to clients of community mental health services. There are indications of effectiveness in reducing disability, although there appears to be negligible effect on symptoms of anxiety and depression. This is the first report of a trial of a low-intensity CBT-based music group intervention. PMID- 28988550 TI - Cognitive profiles in childhood and adolescence differ between adult psychotic and affective symptoms: a prospective birth cohort study. AB - BACKGROUND: Differences between verbal and non-verbal cognitive development from childhood to adulthood may differentiate between those with and without psychotic symptoms and affective symptoms in later life. However, there has been no study exploring this in a population-based cohort. METHOD: The sample was drawn from the MRC National Survey of Health and Development, and consisted of 2384 study members with self-reported psychotic experiences and affective symptoms at the age of 53 years, and with complete cognitive data at the ages of 8 and 15 years. The association between verbal and non-verbal cognition at age 8 years and relative developmental lag from age 8 to 15 years, and both adult outcomes were tested with the covariates adjusted, and mutually adjusted for verbal and non verbal cognition. RESULTS: Those with psychotic experiences [thought interference (n = 433), strange experience (n = 296), hallucination (n = 88)] had lower cognition at both the ages of 8 and 15 years in both verbal and non-verbal domains. After mutual adjustment, lower verbal cognition at age 8 years and greater verbal developmental lag were associated with higher likelihood of psychotic experiences within individuals, whereas there was no association between non-verbal cognition and any psychotic experience. In contrast, those with case-level affective symptoms (n = 453) had lower non-verbal cognition at age 15 years, and greater developmental lag in the non-verbal domain. After adjustment, lower non-verbal cognition at age 8 years and greater non-verbal developmental lag were associated with higher risk of case-level affective symptoms within individuals. CONCLUSIONS: These results suggest that cognitive profiles in childhood and adolescence differentiate psychiatric disease spectra. PMID- 28988552 TI - Change in psychotropic drug use in Norwegian nursing homes between 2004 and 2011. AB - : ABSTRACTBackground:We aimed to assess whether there were any changes in the use of psychotropic drugs in Norwegian nursing homes between 2004 and 2011. Also, we investigated whether the predictors of use of specific psychotropic drug groups have changed. METHODS: We conducted a secondary analysis of two cohort studies of two Norwegian nursing home samples (2004/05 and 2010/11). Multivariate models were applied. RESULTS: We found a significant decrease in the prescription of antipsychotic drugs between 2004 and 2011 (0.63 OR, 95%CI = 0.49-0.82, p < 0.001) even after adjusting for relevant demographic and clinical variables. There are only minor changes for the other psychotropic drugs. We found that (1) the use of specific psychotropic drug groups as well as the number of psychotropic drugs used was associated with more affective symptoms and (2) the use of specific psychotropic drug groups as well as the number of psychotropic drugs used was associated with lower scores on the Physical Self-Maintenance scale. CONCLUSION: This is the first study to show a robust decrease in antipsychotic drug use in nursing home patients with dementia unrelated to possible changes in case mix. The change might be explained by treatment recommendations against its use except in the most severe conditions of aggression or psychosis. Our findings indicate that it takes several years to implement scientific knowledge in clinical practice in nursing homes. PMID- 28988551 TI - Food insecurity, social networks and symptoms of depression among men and women in rural Uganda: a cross-sectional, population-based study. AB - OBJECTIVE: To assess the association between food insecurity and depression symptom severity stratified by sex, and test for evidence of effect modification by social network characteristics. DESIGN: A population-based cross-sectional study. The nine-item Household Food Insecurity Access Scale captured food insecurity. Five name generator questions elicited network ties. A sixteen-item version of the Hopkins Symptom Checklist for Depression captured depression symptom severity. Linear regression was used to estimate the association between food insecurity and depression symptom severity while adjusting for potential confounders and to test for potential network moderators. SETTING: In-home survey interviews in south-western Uganda. SUBJECTS: All adult residents across eight rural villages; 96 % response rate (n 1669). RESULTS: Severe food insecurity was associated with greater depression symptom severity (b=0.4, 95 % CI 0.3, 0.5, P<0.001 for women; b=0.3, 95 % CI 0.2, 0.4, P<0.001 for men). There was no evidence of effect modification by social network factors for women. However, for men who are highly embedded within in their village social network, and (separately) for men who have few poor contacts in their personal network, the relationship between severe food insecurity and depression symptoms was stronger than for men on the periphery of their village social network, and for men with many poor personal network contacts, respectively. CONCLUSIONS: In this population-based study from rural Uganda, food insecurity was associated with mental health for both men and women. Future research is needed on networks and food insecurity-related shame in relation to depression symptoms among food insecure men. PMID- 28988553 TI - Color temperature of light-emitting diode lighting matters for optimum growth and welfare of broiler chickens. AB - Light-emitting diode (LED) light bulbs are becoming more prevalent in broiler production as they are dimmable and more energy efficient than compact fluorescent lamps. Although there is some research on how spectrum of light can affect production, little has been conducted on how it may affect stress, and behavior. To determine how different spectrum of light produced by LED lights could affect production, stress and behavior we raised broilers under either 2700 K (WARM) or 5000 K (COOL) color temperature LED bulbs. To determine stress susceptibility bilateral asymmetry (ASYM, n=128), plasma corticosterone concentrations (CORT, n=40) and heterophil/lymphocyte ratios (HL, n=80) were measured. Fear was measured using tonic immobility (TI, n=128), inversion (INV, n=128) and isolation (ISO, n=128). Weight gain and feed conversion ratio (FCR) were also determined. The COOL birds had lower ASYM (1.65+/-0.08 mm, P=0.001), CORT (5.8+/-1.2 ng/dl, P=0.01) and HL (0.16+/-0.01, P=0.03) than the WARM birds (2.38+/-0.14 mm, 13.4+/-2.7 ng/dl and 0.21+/-0.02, respectively). The COOL birds righted faster during TI (136.2+/-11.1 s, P=0.001), flapped less intensely during INV (4.1+/-0.1 flaps/s, P<0.001) and vocalized less during ISO (45.3+/-2.8 vocalizations, P=0.005) when compared with WARM birds (207.2+/-15.8 s, 4.9+/-0.1 flaps/s and 56.5+/-2.9 vocalizations). The COOL birds (2.89+/-0.03 kg, P=0.02) grew to a heavier weight at the end of 42 day then WARM birds (2.79+/-0.03 kg). The COOL birds (1.54+/-0.03) had better FCR (P=0.02) than WARM birds (1.61+/ 0.01). These results demonstrate that raising broilers under 5000 K LED lights can reduce their stress, fear and increase weight gain when compared with 2700 K. These results indicate that the spectrum of light used for rearing of broilers is not only important for production, but also for welfare of the birds. PMID- 28988554 TI - Reduced satellite cell density and myogenesis in Wagyu compared with Angus cattle as a possible explanation of its high marbling. AB - Mechanisms responsible for excellent marbling in Japanese black cattle, Wagyu, remain to be established. Because both muscle cells and intramuscular adipocytes are developed from mesenchymal progenitor cells during early muscle development, we hypothesized that intramuscular progenitor cells in Wagyu cattle have attenuated myogenic capacity in favor of adipogenesis, leading to high marbling but reduced muscle growth. Biceps femoris muscle biopsy samples were obtained from both Angus (n=3) and Wagyu (n=3) cattle at 12 months of age. Compared with Angus, the density of satellite cells was much lower in Wagyu muscle (by 45.8+/ 10%, P<0.05). Consistently, the formation of myotubes from muscle-derived progenitor cells was also lower (by 64.2+/-12.9%, P<0.05), but adipogenic capacity was greater in Wagyu. The average muscle fiber diameter was larger in Wagyu (by 23.9+/-6.8%, P=0.089) despite less muscle mass, suggesting less muscle fiber formation in Wagyu compared with Angus cattle. Because satellite cells are derived from fetal myogenic cells, the reduction in satellite cell density together with lower muscle fiber formation suggests that myogenesis was attenuated during early muscle development in Wagyu cattle. Given the shared pool of mesenchymal progenitor cells, the attenuated myogenesis likely shifts progenitor cells to adipogenesis during early development, which may contribute to high intramuscular adipocyte formation in Wagyu cattle. PMID- 28988555 TI - Mid-season targeted selective anthelmintic treatment based on flexible weight gain threshold for nematode infection control in dairy calves. AB - The suitability of a single mid-season targeted selective treatment (TST) for gastrointestinal nematodes control, based on flexible average daily weight gain (ADWG) thresholds, was investigated in 23 groups of first grazing season calves. In each group, animals were weighed three times: before turnout, at mid-season and at housing. Just after the first weighing, each group was divided in two homogenous sub-groups in terms of age, breed and weight, and randomly allocated to one of two sub-groups intented for two different mid-season anthelmintic treatment strategies: (1) a treatment of all calves composing the sub-group (whole-group treatment (WT)) or (2) a targeted selective weight gain-based treatment (TST) of the animals showing an individual pre-treatment ADWG inferior to the mean pre-treatment ADWG of the corresponding WT sub-group. Anthelmintic treatment (levamisole 7.5 mg/kg BW) was performed 3 to 4 months after turnout. At housing, two parasitological parameters (the anti-Ostertagia ostertagi antibody level-Ostertagia optical density ratio (ODR) and the pepsinogen level) and a clinical parameter (the breech soiling score) were assessed at individual level in each group. Then, the high exposed groups to gastrointestinal nematode (GIN) were defined as groups for which untreated animals exhibited a mean Ostertagia ODR ?0.7 and among these groups, the ones characterized by high abomasal damage due to Ostertagia for which untreated animals exhibited a mean pepsinogen level ?2.5 U Tyr were also identified. Among TST sub-groups, the treatment ADWG thresholds varied from 338 to 941 g/day and the percentage of treated animals from 28% to 75%. Pre- and post-treatment ADWG as well as parasitological and clinical parameters measured at housing were similar between TST and WT sub groups including the 17 high exposed groups to GIN. Within these 17 groups, the treatment allowed to significantly improve post-treatment ADWG compared with untreated animals. In the six high exposed groups showing mean pepsinogen level ?2.5 U Tyr, the average effect of treatment on post-treatment ADWG was the highest and estimated up to 14 kg after a grazing duration of 4 months. In contrast, in six other groups showing mean Ostertagia ODR<0.7 in untreated animals, no effect of treatment was seen suggesting an absence of production losses related to a low level of GIN infection. This study highlighted the suitability of a convenient mid-season TST strategy for first grazing season calves, based on the use of flexible thresholds of ADWG, allowing similar growth compared with a whole-group treatment while keeping a GIN population in refugia. PMID- 28988556 TI - Effects of pre-weaning housing in a multi-suckling system on performance and carbohydrate absorption of relatively light and heavy piglets around weaning. AB - The low feed intake and stress associated with abrupt weaning in conventional pig farming often result in poor post-weaning performance, which is related to impaired intestinal function. We investigated effects of housing conditions before weaning on performance around weaning of relatively light and heavy piglets. Before weaning, piglets were housed either with five sows and their litters in a multi-suckling (MS) system or in pens with individually housed sows in farrowing crates (FC). After weaning at 4 weeks of age (day 0), 16 groups of four piglets (two light and two heavy litter-mates) were housed under equal conditions in enriched pens. Mannitol (day -5 and day 5) and galactose (day 5) were orally administered as markers for gastrointestinal carbohydrate absorption, and after 20 min a blood sample was taken (sugar absorption test). In addition, BW, feed intake and faecal consistency as an indicator for diarrhoea, were assessed frequently during 2 weeks post-weaning. Pre-weaning housing, weight class and their interaction did not affect post-weaning faecal consistency scores. Weight gain over 2 weeks did not differ between pre-weaning housing treatments, but MS piglets gained more (0.67+/-0.12 kg) than FC piglets (0.39+/ 0.16 kg) between days 2 and 5 post-weaning, P=0.02), particularly in the 'heavy' weight class (interaction, P=0.04), whereas feed intake was similar for both treatments. This indicates a better utilisation of the ingested feed of the MS piglets compared with the FC piglets in the early post-weaning period. Pre weaning mannitol concentrations were unaffected by pre-weaning housing, weight class and their interaction. On day 5 post-weaning, however, MS piglets had a lower plasma concentration of mannitol (320 v. 592 nmol/ml, SEM=132, P=0.04) and galactose (91 v. 157 nmol/ml, SEM=20, P=0.04) than FC piglets, regardless of weight class. In conclusion, MS and FC piglets differed in aspects of post weaning gastrointestinal carbohydrate absorption and in weight gain between days 2 and 5 after weaning, but pre-weaning housing did not affect feed intake, weight gain and measures of faecal consistency over the first 2 weeks after weaning. PMID- 28988557 TI - Effects of dietary inclusion of citrus pulp and rockrose soft stems and leaves on lamb meat quality and fatty acid composition. AB - Meat from lambs finished with high-starch diets often contains low concentration of vaccenic (t11-18:1) and rumenic (c9,t11-18:2) acids and high concentration of t10-18:1. We hypothesized that replacing cereals by dehydrated citrus pulp (DCP) and the inclusion of tanniferous feed sources in oil supplemented diets might reduce the accumulation of t10-18:1 and increase the t11-18:1 and c9,t11-18:2 in lamb meat, without affecting the productive performance. In total, 32 lambs were assigned to four diets which combine two factors: basal diet (BD) (cereals v. DCP) and Cistus ladanifer (CL) (0 v. 150 g/kg dry matter). Feed intake, average daily weight gain and carcass traits were not affected by treatments, except for dressing percentage that was reduced with DCP (P=0.046). Both DCP and C. ladanifer reduced tenderness and juiciness of meat, and C. ladanifer also reduced (P0.05) by diets. However, DCP increased the proportions of odd-chain FA (P=0.005) and several minor biohydrogenation (BH) intermediates in meat lipids. C. ladanifer had few effects on meat FA profile. The proportions of t11-18:1 and c9,t11-18:2 were high in all diets (5.4% and 1.5% of total FA, respectively) and were not influenced by the treatments. Basal diet and CL showed some significant interactions concerning FA composition of intramuscular fat. In diets without C. ladanifer, replacement of cereals by DCP increased the 18:0 (P<0.05) and decreased t10,c12-18:2 (P<0.05), t10-18:1 (P<0.10) and t10-/t11-18:1 ratio (P<0.10) with a large reduction of the individual variation for t10-18:1 and of t10-/t11-18:1 ratio. Combined with cereals, C. ladanifer increased 18:0 and reduced the BH intermediates in meat. Replacement of cereals by DCP seems to promote a more predictable FA profile in lamb meat, reducing the risk of t10 shifted BH pathways in the rumen. PMID- 28988558 TI - Childhood abuse and psychotic experiences - evidence for mediation by adulthood adverse life events. AB - AIMS: We have previously reported an association between childhood abuse and psychotic experiences (PEs) in survey data from South East London. Childhood abuse is related to subsequent adulthood adversity, which could form one pathway to PEs. We aimed to investigate evidence of mediation of the association between childhood abuse and PEs by adverse life events. METHODS: Data were analysed from the South East London Community Health Study (SELCoH, n = 1698). Estimates of the total effects on PEs of any physical or sexual abuse while growing up were partitioned into direct (i.e. unmediated) and indirect (total and specific) effects, mediated via violent and non-violent life events. RESULTS: There was strong statistical evidence for direct (OR 1.58, 95% CI: 1.19-2.1) and indirect (OR 1.51, 95% CI: 1.32-1.72) effects of childhood abuse on PEs after adjustment for potential confounders, indicating partial mediation of this effect via violent and non-violent life events. An estimated 47% of the total effect of abuse on PEs was mediated via adulthood adverse life events, of which violent life events made up 33% and non-violent life events the remaining 14%. CONCLUSIONS: The association between childhood abuse and PEs is partly mediated through the experience of adverse life events in adulthood. There is some evidence that a larger proportion of this effect was mediated through violent life events than non-violent life events. PMID- 28988559 TI - Ram semen deterioration by short-term exposure to high altitude is prevented by improvement of antioxidant status. AB - Ovine reproduction efficiency in herds at high altitude (ha) is lower than that at low altitude (la). In ewes, ha effects are due to hypoxia and oxidative stress. Our aim was to establish the effect of antioxidant vitamin supplementation on semen traits and antioxidant status of rams exposed to short or long time ha. A total of 32 rams native to la (~500 m) were used, 16 were kept at la and the other 16 were brought to ha (~3600 m), where they were placed in the same flock as the ha native rams (n=16). Half of the animals in each group were supplemented daily with vitamins C 600 mg and E 450 IU per os, during the entire experimental period, starting the 4th day after animal's arrival at ha (day 0). At days 0, 30 and 60 of treatment, blood and semen samples were collected for evaluation of antioxidant status and semen standard characteristics. Data were compared within each experimental time by analysis of variance using a general linear model. Elevated concentrations of oxidative stress biomarkers were present in blood from animals maintained at ha. Ejaculates from ha exposed rams showed decreased sperm concentration, progressive motility and viability, in addition to decreased antioxidant status in seminal fluid. A total of 30 days of oral supplementation with vitamins C and E prevented some ha negative effects on semen characteristics, mainly in recently ha exposed rams. It is concluded that exposure of rams to ha negatively affects semen quality, where oxidative stress plays a predominant role. These effects are mainly prevented by oral supplementation of vitamins C and E, which constitutes a simple and cheap alternative to improve semen quality of rams when they are moved to ha. PMID- 28988561 TI - Discussing advance care planning: insights from older people living in nursing homes and from family members. AB - : ABSTRACTBackground:Evidence concerning when and in which manner older people living in nursing homes (NHs) would prefer to discuss advance care planning (ACP) is still scarce. This study explored the attitudes of NH residents and family members toward ACP and their opinions as to the right time to broach the subject, the manner in which it should be approached, and the content of ACP. METHODS: This was a qualitative study using face-to-face interviews with 30 residents (age range 66-94), and 10 family members from 4 Italian NHs. The interviews were analyzed using content analysis. RESULTS: Three main themes were identified: (1) life in the NH, including thoughts about life in a nursing home, residents' concerns, wishes and fears, and communication barriers; (2) future plans and attitudes toward ACP, including attitudes toward planning for the future and plans already made, and attitudes toward and barriers against ACP; (3) contents and manner of ACP, including contents of ACP discussions, the right moment to introduce ACP, with whom it is better to discuss ACP, and attitudes toward advance directives. CONCLUSIONS: ACP was a welcome intervention for the majority of participants, but an individualized assessment of the person's readiness to be involved in ACP is needed. For people with dementia, it is essential to identify the right time to introduce ACP before NH admission. Participants in our study suggested that ACP should include palliative care and practical issues, and that in the NH setting all staff and family members may have a valuable role in ACP. PMID- 28988560 TI - Effects of replacement of Moringa oleifera for berseem clover in the diets of Nubian goats on feed utilisation, and milk yield, composition and fatty acid profile. AB - Replacement of conventional feedstuffs with cheap non-conventional ingredients may improve livestock performance and the quality of their products, particularly milk. The study considered the effects of Moringa oleifera (MO) foliage in replacement of berseem clover (BC) on feed utilisation and lactational performance in Nubian goats. A total of 16 lactating Nubian does, weighing 36.2+/ 0.8 kg, were randomly assigned to four experimental treatments containing 0, 125, 250 and 375 g of MO per kg diet to replace 0 (M0), 25 (M25), 50 (M50) and 75% (M75) of BC (on dry matter (DM) basis) in a quadruplicated 4*4 Latin square design. The MO diets increased (P<0.01) feed intake and nutrient digestibility. Feeding MO diets improved (P<0.01) ruminal volatile fatty acids, acetate and propionate but reduced (P<0.01) valerate and iso-butyrate. Moringa diets increased (P<0.01) serum total protein, albumin and glucose but decreased (P<0.05) cholesterol and triglycerides. Milk yield and energy corrected milk, and milk total solids, fat and energy content were increased (P<0.01) in MO diets. Yields of milk components and energy were greater (P<0.05) for MO diets than for control diet. Milk total saturated fatty acids and athrogenicity index were lower (P<0.01), and unsaturated fatty acids, conjugated fatty acids and UFA/SFA ratio higher (P<0.05) for MO diets. It is concluded that feeding MO to replace 75% DM of BC improved feed utilisation, ruminal fermentation, and milk yield and quality in lactating Nubian goats. PMID- 28988563 TI - Food-Based Dietary Guidelines: a comparative analysis between the Dietary Guidelines for the Brazilian Population 2006 and 2014 - CORRIGENDUM. PMID- 28988562 TI - Epidemiology of hepatitis C virus among hemodialysis patients in the Middle East and North Africa: systematic syntheses, meta-analyses, and meta-regressions. AB - We aimed to investigate hepatitis C virus (HCV) epidemiology among hemodialysis (HD) patients in the Middle East and North Africa (MENA). Our data source was an HCV biological measures database populated through systematic literature searches. Descriptive epidemiologic syntheses, effects meta-analyses and meta regressions, and genotype analyses were conducted. We analyzed 289 studies, including 106 463 HD patients. HCV incidence ranged between 0 and 100% as seroconversion risk, and between 0 and 14.7 per 1000 person-years as incidence rate. The regional pooled mean estimate was 29.2% (95% CI: 25.6-32.8%) for HCV antibody positive prevalence and 63.0% (95% CI: 55.4-70.3%) for the viremic rate. Region within MENA, country income group, and year of data collection were associated with HCV prevalence; year of data collection adjusted odds ratio was 0.92 (95% CI: 0.90-0.95). Genotype diversity varied across countries with four genotypes documented regionally: genotype 1 (39.3%), genotype 2 (5.7%), genotype 3 (29.6%), and genotype 4 (25.4%). Our findings showed that one-third of HD patients are HCV antibody positive and one-fifth are chronic carriers and can transmit the infection. However, HCV prevalence is declining. In context of growing HD patient population and increasing HCV treatment availability, it is critical to improve standards of infection control in dialysis and expand treatment coverage. PMID- 28988564 TI - Perceptions of primary health care service users regarding dental team practices in Brazil. AB - BACKGROUND: The Unified Health System (SUS) is the Brazilian set of public health services that offers global access to health care and disease treatments for all citizens. These services have been evaluated by means of a national survey assessing the users' perceptions.AimTo explore and characterize the SUS users' perceptions regarding primary dental team practices in the five Brazilian geographical regions. METHODS: Descriptive study. The sample consisted of 37 262 subjects. Data were collected by means of the Ministry of Health survey, conducted between 2012 and 2014. Variables used in the present study are associated with SUS users' perspectives of satisfaction, access, and use of services. The study utilized bivariate data analysis, and dichotomous variables were derived for analysis following 95% reliability.FindingsThis study observed similarities and proportionality of perceptions in the Brazilian territory. In most macro-regions, dental teams did not develop an active search for dental treatment absentees. However, the SUS users reported very good and good perceptions, which were homogeneously distributed across five Brazilian regions, thereby showing an overall positive perception of primary dental treatment. PMID- 28988565 TI - Effect of age and gender on carcass traits and meat quality of farmed brown hares. AB - A total of 48 sub-adult hares and adult reproducing farmed hares were used to characterize carcass and meat traits according to the age and gender of animals. With respect to carcass traits, when age increased, the carcass weight significantly increased (2022 to 3391 g; P<0.001), but dressing out percentages did not change. The dissectible fat (1.3% to 2.2%; P<0.05) and Longissimus lumborum (LL) proportions (13.5% to 14.5%; P<0.001) and muscle-to-bone ratio of hind legs (5.11 to 6.23; P<0.001) increased, whereas the hind leg proportions decreased (37.3% to 36.3%; P=0.01). As for the meat quality, the pH of hind leg (5.74 to 5.83; P<0.001) and LL (5.53 to 5.69; P<0.001) increased with age, while the L* index decreased in both cuts (42.9 to 34.4 in hind leg; 45.1 to 40.3 in LL; P<0.001). The redness index increased at the hind leg (4.07 to 5.76; P<0.001), while it decreased at LL (3.03 to 1.46; P<0.001). In the case of the hind leg, meat thawing losses decreased (1.58% to 1.02%), and shear force increased (2.97 to 4.02 kg/g). In the case of LL, thawing losses decreased (8.79% to 4.91%; P<0.001) in the adult hares compared with the sub-adult ones. Meat water and protein contents decreased in the hind leg and LL of the adult hares compared with the sub-adult ones, whereas ether extract increased in a restricted range in LL only (0.92% to 1.11%; P<0.001). In the case of the hind leg, the rate of the saturated fatty acids (SFA) decreased (41.0% to 26.7%), and the rate of the polyunsaturated fatty acids (PUFA) increased (34.0% to 45.3%) (P<0.001). In the case of LL, SFA (38.6% to 42.9%) and monounsaturated fatty acids (19.4% to 27.2%) increased, whereas PUFA decreased (42.0% to 30.1%) when the age increased (P<0.001). Gender affected only the slaughter results and carcass traits. In conclusion, farmed hares have favourable slaughter results (high dressing percentage), carcass traits (high hind legs and loins rates), and meat nutritional value (high-protein, low-fat meat). This fact would offer additional commercial opportunities, in addition to restocking, to hare farmers. PMID- 28988566 TI - Prediction of effects of beef selection indexes on greenhouse gas emissions. AB - Genetic improvement in production efficiency traits can also drive reduction in greenhouse gas emissions. This study used international 'best-practice' methodology to quantify the improvements in system-wide CO2 equivalent emissions per unit of genetic progress in the Irish Maternal Replacement (MR) and Terminal (T) beef cattle indexes. Effects of each index trait on system gross emissions (GE) and system emissions intensity (EI) were modelled by estimating effects of trait changes on per-animal feed consumption and associated methane production, per-animal meat production and numbers of animals in the system. Trait responses to index selection were predicted from linear regression of individual bull estimated breeding values for each index trait on their MR or T index value, and the resulting regression coefficients were used to calculate trait-wise responses in GE and EI from index selection. Summed over all trait responses, the MR index was predicted to reduce system GE by 0.810 kg CO2e/breeding cow per year per ? index and system EI by 0.009 kg CO2e/kg meat per breeding cow per year per ? index. These reductions were mainly driven by improvements in cow survival, reduced mature cow maintenance feed requirements, shorter calving interval and reduced offspring mortality. The T index was predicted to reduce system EI by 0.021 kg CO2e/kg meat per breeding cow per year per ? index, driven by increased meat production from improvements in carcass weight, conformation and fat. Implications for incorporating an EI reduction index to the current production indexes and long-term projections for national breeding programs are discussed. PMID- 28988567 TI - SFA intake among Japanese schoolchildren: current status and possible intervention to prevent excess intake. AB - OBJECTIVE: Although a high intake of fat, particularly SFA, is a well-known risk factor for CVD, fat intake in Japan has attracted relatively little attention from health professionals to date due to the low intake in the Japanese population. However, recent surveys have shown an increase in fat intake in younger Japanese populations. Here, we described the fat intake and dietary sources of SFA in Japanese schoolchildren. Also, we experimentally exchanged a high-SFA food with a low-SFA substitute in the data, and calculated the resulting changes in nutrient intakes. DESIGN: The study was conducted nationwide under a cross-sectional design. A non-consecutive, three-day diet record was performed on two school days and a non-school day. SETTING: Fourteen elementary and thirteen junior high schools. SUBJECTS: Elementary-school children (n 629) and junior high school children (n 281). RESULTS: Prevalence of excess fat intake was 35.4 % in boys and 45.0 % in girls. Excess SFA intake was suspected in 97.7 % of boys and 99.4 % of girls when the dietary reference intake values for adults were applied. Major dietary sources of SFA were meat (26.4 % of total SFA intake), dairy products (25.7 %) and confectioneries (11.3 %). CONCLUSIONS: Since one-third to nearly one-half of our Japanese schoolchildren consumed excess fat, careful monitoring of fat intake in the Japanese population should be continued. Adoption of low-fat milk and/or lean meat in daily meals might be a suitable means of reducing fat, particularly SFA intake, in schoolchildren. PMID- 28988568 TI - Does the accreditation of private dental practices work? Time to rethink how accreditation can improve patient safety. AB - Accreditation to demonstrate engagement with the National Safety and Quality Health Service Standards (Standards) is compulsory for most hospital and healthcare settings, but to date remains voluntary for private dental practices (PDPs). The regulatory framework governing the dental profession lacks a proactive element to drive improvements in quality and safety of care, and an accreditation scheme can strengthen existing regulation. The current model of accreditation operating in accordance with the Australian Health Service Safety and Quality Accreditation Scheme (Scheme) is based on the Standards, which were written for a hospital model of healthcare service. The majority of PDPs are small office-based businesses with clear leadership structure and employing six staff or fewer. The Scheme is overly bureaucratic given the simplicity of the PDP business model. This article considers whether accreditation has a proven track record of improving quality of service and offers opinions about how a more appropriate safety management program for PDPs may look.What is known about the topic? There has been minimal research about the impact of accreditation schemes in improving patient safety in PDP.What does this paper add? This paper proposes a redesign of the Scheme to make it more relevant to PDPs. The paper offers strategies to minimise duplication of purpose between accreditation and existing legislation; and to strengthen critical elements of accreditation to improve effects on patient safety.What are the implications for practitioners? A redesigned accreditation scheme will support dental practitioners to implement a quality assurance system with improved efficiency, reduced administrative burden, and optimised patient safety. PMID- 28988569 TI - Public reporting of hospital performance data: views of senior medical directors in Victoria, Australia. AB - Objective The aim of the present study was to better understand senior medical directors' perceptions of public reporting of hospital performance data, how public reporting affects institutional behavioural change towards quality improvement and how it could be improved.Methods Interviews were undertaken with 17 medical directors representing 26 metropolitan and regional public hospitals in Victoria, Australia, between June and August 2016. Data were analysed thematically.Results Medical directors are well placed to comment on clinical and administrative aspects of quality, safety and performance monitoring in public hospitals. Their responses largely suggested that public reporting of hospital performance data in Australia is immature and not fulfilling its potential. There was little consensus among informants around what public reporting is, who it is for or its purpose. Although public reporting was considered to have important functions for hospitals and consumers, it was generally considered to lack robustness and have underutilised potential to inform consumers, build trust and drive quality and performance improvements within hospitals.Conclusions The next steps needed to advance public reporting of hospital performance data in Australia include engaging clinicians and patients in selection and development of metrics, improving timeliness of reporting, and improving communication of information so that it is accessible and meaningful for different audiences.What is known about the topic? Public reporting of hospital performance data is a mechanism increasingly used in the Australian health system, but it has attracted little research.What does this paper add? This paper reveals a lack of shared understanding among medical directors in Victoria, Australia, on what public reporting of hospital performance data is, who it is for and its purpose. The paper highlights the potential importance of public reporting of hospital performance data for rural and regional healthcare consumers and how it may be strengthened.What are the implications for practitioners? Stronger systems of public reporting of hospital performance data have the potential to increase consumer engagement and improve hospital performance, quality and safety. Awareness of the discourse around public reporting of hospital performance data can increase practitioners' engagement in debate and development of reporting systems. PMID- 28988570 TI - Alcoholic Liver Disease: Pathogenesis and Current Management. AB - Excessive alcohol consumption is a global healthcare problem. The liver sustains the greatest degree of tissue injury by heavy drinking because it is the primary site of ethanol metabolism. Chronic and excessive alcohol consumption produces a wide spectrum of hepatic lesions, the most characteristic of which are steatosis, hepatitis, and fibrosis/cirrhosis. Steatosis is the earliest response to heavy drinking and is characterized by the deposition of fat in hepatocytes. Steatosis can progress to steatohepatitis, which is a more severe, inflammatory type of liver injury. This stage of liver disease can lead to the development of fibrosis, during which there is excessive deposition of extracellular matrix proteins. The fibrotic response begins with active pericellular fibrosis, which may progress to cirrhosis, characterized by excessive liver scarring, vascular alterations, and eventual liver failure. Among problem drinkers, about 35 percent develop advanced liver disease because a number of disease modifiers exacerbate, slow, or prevent alcoholic liver disease progression. There are still no FDA approved pharmacological or nutritional therapies for treating patients with alcoholic liver disease. Cessation of drinking (i.e., abstinence) is an integral part of therapy. Liver transplantation remains the life-saving strategy for patients with end-stage alcoholic liver disease. PMID- 28988571 TI - Alcohol and Gut-Derived Inflammation. AB - In large amounts, alcohol and its metabolites can overwhelm the gastrointestinal tract (GI) and liver and lead to damage both within the GI and in other organs. Specifically, alcohol and its metabolites promote intestinal inflammation through multiple pathways. That inflammatory response, in turn, exacerbates alcohol induced organ damage, creating a vicious cycle and leading to additional deleterious effects of alcohol both locally and systemically. This review summarizes the mechanisms by which chronic alcohol intake leads to intestinal inflammation, including altering intestinal microbiota composition and function, increasing the permeability of the intestinal lining, and affecting the intestinal immune homeostasis. Understanding the mechanisms of alcohol-induced intestinal inflammation can aid in the discovery of therapeutic approaches to mitigate alcohol-induced organ dysfunctions. PMID- 28988572 TI - Uniting Epidemiology and Experimental Disease Models for Alcohol-Related Pancreatic Disease. AB - Findings from epidemiologic studies and research with experimental animal models provide insights into alcohol-related disease pathogeneses. Epidemiologic data indicate that heavy drinking and smoking are associated with high rates of pancreatic disease. Less clear is the association between lower levels of drinking and pancreatitis. Intriguingly, a very low percentage of drinkers develop clinical pancreatitis. Experimental models demonstrate that alcohol administration alone does not initiate pancreatitis but does sensitize the pancreas to disease. Understanding the effects of alcohol use on the pancreas may prove beneficial in the prevention of both pancreatitis and pancreatic cancer. PMID- 28988574 TI - Alcoholic Myopathy: Pathophysiologic Mechanisms and Clinical Implications. AB - Skeletal muscle dysfunction (i.e., myopathy) is common in patients with alcohol use disorder. However, few clinical studies have elucidated the significance, mechanisms, and therapeutic options of alcohol-related myopathy. Preclinical studies indicate that alcohol adversely affects both anabolic and catabolic pathways of muscle-mass maintenance and that an increased proinflammatory and oxidative milieu in the skeletal muscle is the primary contributing factor leading to alcohol-related skeletal muscle dysfunction. Decreased regenerative capacity of muscle progenitor cells is emerging as an additional mechanism that contributes to alcohol-induced loss in muscle mass and impairment in muscle growth. This review details the epidemiology of alcoholic myopathy, potential contributing pathophysiologic mechanisms, and emerging literature on novel therapeutic options. PMID- 28988575 TI - Alcohol's Effects on the Cardiovascular System. AB - Alcohol use has complex effects on cardiovascular (CV) health. The associations between drinking and CV diseases such as hypertension, coronary heart disease, stroke, peripheral arterial disease, and cardiomyopathy have been studied extensively and are outlined in this review. Although many behavioral, genetic, and biologic variants influence the interconnection between alcohol use and CV disease, dose and pattern of alcohol consumption seem to modulate this most. Low to-moderate alcohol use may mitigate certain mechanisms such as risk and hemostatic factors affecting atherosclerosis and inflammation, pathophysiologic processes integral to most CV disease. But any positive aspects of drinking must be weighed against serious physiological effects, including mitochondrial dysfunction and changes in circulation, inflammatory response, oxidative stress, and programmed cell death, as well as anatomical damage to the CV system, especially the heart itself. Both the negative and positive effects of alcohol use on particular CV conditions are presented here. The review concludes by suggesting several promising avenues for future research related to alcohol use and CV disease. These include using direct biomarkers of alcohol to confirm self report of alcohol consumption levels; studying potential mediation of various genetic, socioeconomic, and racial and ethnic factors that may affect alcohol use and CV disease; reviewing alcohol-medication interactions in cardiac patients; and examining CV effects of alcohol use in young adults and in older adults. PMID- 28988576 TI - Alcohol and the Lung. AB - Among the many organ systems affected by harmful alcohol use, the lungs are particularly susceptible to infections and injury. The mechanisms responsible for rendering people with alcohol use disorder (AUD) vulnerable to lung damage include alterations in host defenses of the upper and lower airways, disruption of alveolar epithelial barrier integrity, and alveolar macrophage immune dysfunction. Collectively, these derangements encompass what has been termed the "alcoholic lung" phenotype. Alcohol-related reductions in antioxidant levels also may contribute to lung disease in people with underlying AUD. In addition, researchers have identified several regulatory molecules that may play crucial roles in the alcohol-induced disease processes. Although there currently are no approved therapies to combat the detrimental effects of chronic alcohol consumption on the respiratory system, these molecules may be potential therapeutic targets to guide future investigation. PMID- 28988573 TI - Alcohol's Effects on the Brain: Neuroimaging Results in Humans and Animal Models. AB - Brain imaging technology has allowed researchers to conduct rigorous studies of the dynamic course of alcoholism through periods of drinking, sobriety, and relapse and to gain insights into the effects of chronic alcoholism on the human brain. Magnetic resonance imaging (MRI) studies have distinguished alcohol related brain effects that are permanent from those that are reversible with abstinence. In support of postmortem neuropathological studies showing degeneration of white matter, MRI studies have shown a specific vulnerability of white matter to chronic alcohol exposure. Such studies have demonstrated white matter volume deficits as well as damage to selective gray-matter structures. Diffusion tensor imaging (DTI), by permitting microstructural characterization of white matter, has extended MRI findings in alcoholics. MR spectroscopy (MRS) allows quantification of several metabolites that shed light on brain biochemical alterations caused by alcoholism. This article focuses on MRI, DTI, and MRS findings in neurological disorders that commonly co-occur with alcoholism, including Wernicke's encephalopathy, Korsakoff's syndrome, and hepatic encephalopathy. Also reviewed are neuroimaging findings in animal models of alcoholism and related neurological disorders. This report also suggests that the dynamic course of alcoholism presents a unique opportunity to examine brain structural and functional repair and recovery. PMID- 28988577 TI - Pathophysiology of the Effects of Alcohol Abuse on the Endocrine System. AB - Alcohol can permeate virtually every organ and tissue in the body, resulting in tissue injury and organ dysfunction. Considerable evidence indicates that alcohol abuse results in clinical abnormalities of one of the body's most important systems, the endocrine system. This system ensures proper communication between various organs, also interfacing with the immune and nervous systems, and is essential for maintaining a constant internal environment. The endocrine system includes the hypothalamic-pituitary-adrenal axis, the hypothalamic-pituitary gonadal axis, the hypothalamic-pituitary-thyroid axis, the hypothalamic-pituitary growth hormone/insulin-like growth factor-1 axis, and the hypothalamic-posterior pituitary axis, as well as other sources of hormones, such as the endocrine pancreas and endocrine adipose tissue. Alcohol abuse disrupts all of these systems and causes hormonal disturbances that may result in various disorders, such as stress intolerance, reproductive dysfunction, thyroid problems, immune abnormalities, and psychological and behavioral disorders. Studies in both humans and animal models have helped shed light on alcohol's effects on various components of the endocrine system and their consequences. PMID- 28988578 TI - Alcohol and Puberty. AB - Adolescence represents a vulnerable period for developing youth. Alcohol use and misuse are especially problematic behaviors during this time. Adolescents are more sensitive to alcohol and less tolerant of its detrimental effects than are adults. Research in humans and animals has revealed that early alcohol consumption can result in delayed pubertal development. Animal studies have shown that alcohol detrimentally affects neuroendocrine systems within the hypothalamic region of the brain that are associated with the normal, timely onset of the pubertal process. To effectively restore development and shorten recovery time associated with the adverse effects of alcohol on puberty, researchers must first understand the molecular and physiological mechanisms by which alcohol interferes with critical hypothalamic functions. PMID- 28988579 TI - Alcohol Misuse and Kidney Injury: Epidemiological Evidence and Potential Mechanisms. AB - Chronic alcohol consumption is a well-known risk factor for tissue injury. The link between alcohol use disorder (AUD) and kidney injury is intriguing but controversial, and the molecular mechanisms by which alcohol may damage the kidneys are poorly understood. Epidemiological studies attempting to link AUD and kidney disease are, to date, inconclusive, and there is little experimental evidence directly linking alcohol consumption to kidney injury. However, studies conducted primarily in other organs and tissues suggest several possible mechanisms by which alcohol may promote kidney dysfunction. One possible mechanism is oxidative stress resulting from increased production of reactive oxygen species, which leads to an excessive amount of free radicals, which in turn trigger tissue injury and increase inflammation. In addition, AUD's effect on other major organs (liver, heart, intestines, and skeletal muscle) appears to promote unfavorable pathological processes that are harmful to the kidneys. Notably, these mechanisms have not yet been validated experimentally in the kidney. Additional research is needed to clarify if alcohol does indeed promote kidney injury and the mechanisms by which alcohol-induced kidney injury may occur. PMID- 28988581 TI - Rupture of Subcutaneous Peritoneal Dialysis Catheter by Stretching Exercise: A Case Report. AB - Rupture of the peritoneal dialysis (PD) catheter is rare complication. Here, we report a case of catheter rupture that occurred because of exercise after partial catheter reimplantation.A 66-year-old man with a history of end-stage kidney disease secondary to diabetic nephropathy experienced refractory exit-site and tunnel infection. After the infected parts of the catheter were excised, a partial catheter reimplantation was performed. At the time of that surgery, a presternal location was selected for the new exit site, and a titanium extender was used to connect the two catheters. The patient was discharged on postoperative day 3, but was readmitted for a pericatheter leak 5 days later. Fluoroscopy performed to investigate the cause demonstrated a pericatheter leak from the connecting portion between the titanium extender and the catheter.Surgery performed to repair the leak revealed that the catheter had ruptured. We believe that the cause of the rupture was mechanical stress induced by the patient's stretching exercise program. The PD catheter was made of silicone rubber with high elasticity. Even when such resilient materials are used, we recommend that, to avoid PD catheter rupture after partial reimplantation, clinicians should discourage the patient from stretching excessively. PMID- 28988582 TI - Correlation Between Near-Vision Acuity and the Incidence of Peritoneal Dialysis Related Infections. AB - Peritoneal dialysis (PD)-related infections (PDIs) such as peritonitis, exit-site infection, and tunnel infection are serious complications affecting patients on PD. Because patients with diabetes (DM) and of older age have increased in number in Japan, the number of patients with visual impairment is estimated also to have increased. Near vision is necessary for performing proper PD daily care. However, no studies have reported whether visual impairment is likely to increase the risk of PDIs.Our study included 31 PD patients (16 men, 15 women; mean age: 61.5 +/- 11.8 years; mean PD duration: 27.3 +/- 20.3 months; 38.7% with DM; 54.8% wearing glasses) who performed their own PD care. At our facility and related facilities, we used a standard near-vision test chart, which classifies vision into 12 grades, from 0.1 (poor) to 1.5 (clear), to assess near-vision binocular visual acuity in those patients between March 2015 and September 2015. In addition, we retrospectively examined the medical records of the patients to determine their history of PDIs. We then evaluated the correlation between near-vision acuity and the incidence of PDIs.Mean measured near-vision acuity was 0.61 +/- 0.29, and we observed no significant difference in the visual acuity of patients with and without DM (0.55 +/- 0.31 vs. 0.63 +/- 0.26 respectively, p = 0.477). In addition, we observed no significant difference in the incidence of PDIs between patients with and without DM (1.298 +/- 1.609 per year vs. 1.164 +/- 0.908 per year respectively, p = 0.804). We did not find a correlation between near-vision acuity and the incidence of PDIs (r = -0.071, p = 0.795). PMID- 28988583 TI - Louisiana State University Nephrology: Initiation of a Multicenter Urgent-Start Peritoneal Dialysis Program. AB - Urgent-start peritoneal dialysis (PD) refers to the initiation of PD in new-start end-stage renal disease patients who present either emergently in the hospital or urgently in clinic. These patients are called "late-referred patients." Our academic practice group, like many private practice and academic groups, currently functions within 4 hospitals and 4 clinics. The patient base consists of a large indigent population with limited access to health care and also of insured patients. An urgent-start PD program was initiated to provide all patients with a choice of dialysis modality.Our faculty understood that, for their urgent-start PD program to be successful, they had to have the support of the house staff, hospitalists, surgeons, and the PD nurse. The education began with grand rounds on urgent-start PD in the medicine department. We also educated the hospitalists at the other private hospitals on our urgent-start program. Once the primary care services were comfortable with urgent-start PD, our nephrology group then educated the surgeons about best-practice guidelines for PD catheter placement. At that time, a direct feedback communication loop was created between the PD nurse, surgeon, and nephrologist about the placement and functionality of the catheter. Here, we present our success in the creation of an urgent-start PD program. PMID- 28988580 TI - Development, Prevention, and Treatment of Alcohol-Induced Organ Injury: The Role of Nutrition. AB - Alcohol and nutrition have the potential to interact at multiple levels. For example, heavy alcohol consumption can interfere with normal nutrition, resulting in overall malnutrition or in deficiencies of important micronutrients, such as zinc, by reducing their absorption or increasing their loss. Interactions between alcohol consumption and nutrition also can affect epigenetic regulation of gene expression by influencing multiple regulatory mechanisms, including methylation and acetylation of histone proteins and DNA. These effects may contribute to alcohol-related organ or tissue injury. The impact of alcohol-nutrition interactions has been assessed for several organs and tissues, including the intestine, where heavy alcohol use can increase intestinal permeability, and the liver, where the degree of malnutrition can be associated with the severity of liver injury and liver disease. Alcohol-nutrition interactions also play a role in alcohol-related lung injury, brain injury, and immune dysfunction. Therefore, treatment involving nutrient supplementation (e.g., with zinc or S adenosylmethionine) may help prevent or attenuate some types of alcohol-induced organ damage. PMID- 28988584 TI - Erosion of the Silicone Peritoneal Dialysis Catheter with the Use of Gentamicin Cream at the Exit Site. AB - Infection remains the leading complication of peritoneal dialysis (PD). Topical mupirocin and gentamicin are frequently used to prevent infections. Mupirocin ointment has been reported to cause damage to both polyurethane and silicone PD catheters. Gentamicin cream has not been associated with physical damage to catheters.A 64-year-old woman on PD developed relapsing peritonitis with Staphylococcus epidermidis. Because of a drainage problem and white discoloration at the exit site, which is known as " frosting," she underwent catheter exchange. The catheter was found to be fractured within the area of frosting. Four more patients with frosting of the catheter were identified. On further questioning, it was recognized that they were applying excessive amounts of gentamicin cream directly on the catheter surface rather than at the exit site. All patients in the program were educated about the correct method of topical antibiotic application. After the change in practice, no further cases of catheter frosting were identified.Polyurethane catheters can undergo oxidation, mineralization, and environmental stress cracking, leading to physical damage such frosting, ballooning, and fracture. Polyethylene glycol, a component of the mupirocin ointment base, is thought to cause plasticization of polyurethane, reducing its tensile strength. Similar damage has been observed in silicone catheters. Previous reports have not found gentamicin cream to cause that type of damage. We observed that excessive amounts of cream applied directly to the catheter surface can damage it. Damage did not recur once patients had been educated about the proper method of application. PMID- 28988585 TI - Time Is Not Always the Matter: An Instance of Encapsulating Peritoneal Sclerosis Developing in a Patient on Peritoneal Dialysis for a Short Term. AB - Encapsulating peritoneal sclerosis (EPS) is an infrequent but serious complication that is observed mostly in patients on long-term peritoneal dialysis (PD). However it can occur after short-term PD, in association with "second hit" risk factors such as peritonitis, acute cessation of PD, or kidney transplantation with the use of calcineurin inhibitors.In our case, a young woman with second-hit risk factors presented with clinical and abdominal computed tomography findings consistent with EPS after short-term PD. She was treated conservatively with nutritional support and was discharged in improved and stable clinical status.In general, the diagnosis of EPS requires clinical findings of bowel obstruction combined with typical computed tomography imaging features. However, the clinical manifestations can be very vague, and the diagnosis is often unclear. A recent study categorized EPS into 4 clinical stages, from pre EPS to chronic ileus, with associated management from conservative treatment to surgical intervention.In association with second-hit risk factors, EPS can occur after short-term PD. Severity is variable, and the outcome is often devastating. Timely recognition and expert management of EPS can change the outcome very favorably. PMID- 28988586 TI - Comparing Dialysis Modality and Cardiovascular Mortality in Patients on Hemodialysis and Peritoneal Dialysis. AB - Patients undergoing dialysis are at high risk for cardiovascular disease (CVD). Mortality differences between peritoneal dialysis (PD) and hemodialysis (HD) are widely debated. The question of whether dialysis modality affects the risk for CVD remains to be addressed.In the present study, we evaluated the influence of hemodialysis (HD) and peritoneal dialysis (PD) on survival and the risk of developing de novo CVD. Our observational prospective study enrolled 157 end stage renal disease patients on HD or PD for 12 months. Patients with a history of malignancy, chronic rheumatic heart disease, congenital heart disease, previous cardiac surgery, or previous transplantation, and patients started on dialysis less than 3 months earlier were excluded from the study. Detailed medical history, demographic data, and routine laboratory investigations were obtained, and patients were follow every 3 months for 12 months. Cardiac echography was performed at baseline and at 6 months. Nutrition status was scored using the standardized 7-point subjective global assessment (SGA). Baseline comorbidities included the presence or absence of coronary artery disease (angina, myocardial infarction, and coronary artery bypass surgery), peripheral vascular disease, hypertension, diabetes mellitus, and cerebrovascular disease.Of the 157 patients, 121 were on HD (60 men, 61 women; mean age: 59.3 years), and 36 were on PD (14 men, 22 women; mean age: 50.8 years, p = 0.13). The dialysis duration was significantly different in the two groups (HD: 52.96 +/- 38.3; PD: 30.89 +/- 26.3; p = 0.02). Of the HD patients, 95.04% were hypertensive, and 61.98% were diabetic; of the PD patients, 91.66% were hypertensive, and 50% were diabetic. Body mass index and SGA score were not significantly different between the two groups. Patients on PD had a higher residual urine volume (383.66 +/- 548.393 mL vs. 12.40 +/- 96.238 mL in the HD patients, p < 0.001).In comparing traditional cardiovascular risk factors at the start of the study, PD patients had higher levels of total cholesterol (4.5 +/- 1.33 mmol/L vs. 3.85 +/- 1.34 mmol/L in HD patients, p < 0.05), low-density lipoprotein cholesterol (2.84 +/- 1.31 mmol/L vs. 2.06 +/- 0.89 mmol/L, p < 0.001), high-density lipoprotein cholesterol (1.10 +/- 0.26 mmol/L vs. 0.91 +/- 0.32 mmol/L, p < 0.005). Cardiovascular morbidity affected 17 HD patients and 2 PD patients. A Cox proportional hazards model for cardiovascular events showed a trend suggesting that PD was safer, but the data did not reach statistical significance. Kaplan Meir survival analysis revealed 12 death events in HD patients compared with 4 events in PD patients-a difference that was not statistically significant.Cardiovascular morbidity during chronic dialysis was prevalent among the older patients (>57 years) and those who used more than 1 antihypertensive medication; an ejection fraction exceeding 53% was found to be cardioprotective. For all-cause mortality, dialysis modality was a nonsignificant risk factor; age and Kt/V were significant. PMID- 28988587 TI - Preoperative Cardiac Evaluation in Kidney Transplant Patients: Is Coronary Angiography Superior? A Focused Review. AB - Cardiovascular disease is the major cause of morbidity and mortality in chronic kidney disease patients. Because of a higher occurrence of asymptomatic coronary artery disease and increased perioperative cardiovascular mortality in kidney transplant patients, screening for coronary artery disease before transplant surgery is essential. Various studies have shown that cardiac stress testing is an unreliable screening method in these patients because of significant variability in sensitivity and negative predictive value. We suggest that high risk candidates such as those with diabetes or a prior history of myocardial infarction, stroke, peripheral vascular disease, or coronary artery disease should perhaps be considered for coronary angiography rather than stress testing as cardiac screening before kidney transplantation. PMID- 28988588 TI - Role of Chronic Use of Tolvaptan in Patients with Heart Failure Undergoing Peritoneal Dialysis. AB - In the present study, we assessed the effect of chronic tolvaptan treatment and compared it with the effect of conventional treatment without tolvaptan. In addition, changes in cardiac load and body fluid composition were compared.The study enrolled 22 patients undergoing peritoneal dialysis who had been receiving tolvaptan for more than 1 year and 10 patients undergoing peritoneal dialysis who had been treated with conventional diuretics. Left ventricular mass index (LVMI), left ventricular ejection fraction (LVEF), and E/e' index were measured by echocardiography at baseline and after 12 months of tolvaptan treatment (or an equivalent period). Body composition was analyzed by bioimpedance monitoring (BIM).In the tolvaptan group, LVMI was significantly reduced after 12 months of treatment; in the conventional-treatment group, it was significantly increased. The measured LVEF did not change in the tolvaptan group, but it increased significantly in the conventional-treatment group. The E/e' index was not altered in either group; however, it was reduced in patients receiving tolvaptan whose initial E/e' was greater than 15. Although urine volume was not significantly increased in either group, renal creatinine clearance increased significantly in tolvaptan group; no change was observed in the conventional-treatment group. Renal and peritoneal Kt/V did not significantly change during the study. In both groups, beta2-microglobulin was significantly and similarly increased. Extracellular water (ECW) and intracellular water (ICW) as determined by BIM were both reduced after 12 months of tolvaptan treatment. We observed a significant correlation between the ratio of ECW to total body water at the initiation of tolvaptan and the reduction in ECW after 12 months.Our results indicate that chronic tolvaptan treatment has a beneficial role in body fluid control without a reduction in cardiac and renal function. Volume control depends on an equal reduction in ECW and ICW, which can also have a benefit in avoiding hyponatremia. PMID- 28988589 TI - Efficacy and Biocompatibility of Neutral Icodextrin Peritoneal Dialysis Fluid. AB - Neutral icodextrin peritoneal dialysis (PD) fluid (n-ICO) has become available for use in Japan. However, removal of water and solutes remains to be elucidated in detail. The present study was designed to determine removal of water, electrolytes, and small, middle, and large molecules in a period of 16 hours. In addition, biocompatibility with respect to peritoneal mesothelial cells was determined.Three stable patients undergoing PD at Tohoku University Hospital were administered n-ICO. Water removal was monitored every 2 hours. Sodium, urea nitrogen [molecular weight (MW): 28 Da], uric acid (MW: 168 Da), beta2 microglobulin [beta2M (MW: 11,800 Da)], alpha1-microglobulin [alpha1M (MW: 33,000 Da)], albumin (MW: 66,000 Da), and immunoglobulin G (MW: 160,000 Da) were measured in plasma and dialysate.Primary human peritoneal mesothelial cells were collected from 6 patients. Equal numbers of cells were seeded into 96-well culture plates and cultured for 12 hours. Culture medium was then replaced with dialysate, and 24-hour cell proliferation was determined by WST-1 assay.Water removal was sustained for 16 hours with n-ICO. The Na concentration in effluent did not change over that time. Small molecules such as urea nitrogen and uric acid were rapidly removed. Thus, their dialysate-to-plasma concentration ratio (D/P) approached 1.0 (equilibrium) in 2 - 4 hours. The D/P values for the larger molecules beta2M and alpha1M were 0.4 and less than 0.1 respectively at 16 hours. However, larger molecules were removed in a time-dependent manner.Cell proliferation with n-ICO PD fluid was not different from that with lactate buffered glucose PD fluid, but was increased from that with acidic icodextrin PD fluid (a-ICO).Water and solute removal with the new n-ICO is not much different from that with a-ICO. However, biocompatibility as reflected by cell proliferation was superior under n-ICO than under a-ICO and equal to proliferation under glucose PD fluid. PMID- 28988590 TI - Treatment of Calciphylaxis: A Case for Oral Sodium Thiosulfate. AB - Calciphylaxis is a major cause of morbidity and mortality in end-stage renal disease (ESRD). Intravenous sodium thiosulfate (STS) is the mainstay of therapy for calciphylaxis. In peritoneal dialysis (PD) patients with calciphylaxis, intravenous STS poses logistic and financial challenges. Even though pharmacokinetic studies show poor bioavailability of oral STS, we report successful use of oral STS in 2 PD patients with calciphylaxis.A 55-year-old Latina American woman with diabetes was initiated on PD after access failure and chronic hypotension. She developed painful ischemic lesions in the left middle finger and left big toe 4 months later. The ischemia in the left hand progressed, requiring amputation of two fingers. She later developed extensive painful calcific areas in the abdominal wall. She was initially started on oral STS 1500 mg twice daily that was subsequently increased to 3750 mg daily, which resulted in substantial pain relief and a decrease in the size of the calcific plaques.Another diabetic patient with ESRD who was on PD presented with a painful ischemic finger for 2 years. He was treated with oral STS 1500 mg twice daily, resulting in prompt pain relief.Oral STS can be an effective treatment for calciphylaxis. PMID- 28988591 TI - Bullous Skin Lesions in a Patient with End-Stage Renal Disease and Hepatitis C. AB - Bullous lesions in patients with end-stage renal disease are uncommon and can pose diagnostic and therapeutic challenges. We present a female patient with end stage renal disease, bullous skin lesions affecting mainly sun-exposed areas, and high ferritin levels. She also had hepatitis C. Her serum porphyrin panel was suggestive of porphyria cutanea tarda. Skin biopsy excluded inflammatory pathologies. Phlebotomy during each hemodialysis, continuation of darbepoetin, and avoidance of any further doses of intravenous iron, with close monitoring of hemoglobin, resulted in a gradual drop in ferritin level and improvement of the skin lesions. PMID- 28988592 TI - Successful Peritoneal Dialysis in Large-Weight Subjects: Clinical Features and Comparisons with Normal-Weight Subjects. AB - Peritoneal dialysis (PD) obviates the need for temporary vascular access in end stage renal disease; however, extremely heavy weight has been viewed as a relative contraindication to PD.We performed a cross-sectional review of multiple clinical and laboratory variables for 75 current or past PD patients (vintage > 6 months), comparing dialysis adequacy parameters for those with a large body weight (>100 kg, LWS group) and with a normal body weight (<75 kg, NWS group).In the LWS group (n = 17), mean weight was 117.2 +/- 15.7 kg, and mean body mass index (BMI) was 37.2 +/- 6.3 kg/m2; in the NWS group (n = 33), mean weight was 63.2 +/- 9.2 kg, and mean BMI was 25.3 +/- 4.5 kg/m2. Despite the marked differences in weight and BMI between the groups (both p < 0.0001), achieved Kt/V was adequate, although marginally less, in large subjects (1.96 +/- 0.29 for the LWS group vs. 2.22 +/- 0.47 for the NWS group, p = 0.022), and weekly global creatinine clearance was significantly better in the LWS group (92.5 +/- 43.5 L/1.73 m2 vs. 62.2 +/- 27.5 L/1.73 m2, p = 0.016). The total daily exchange volume was approximately 30% higher in the LWS group (12.8 +/- 2.5 L vs. 9.9 +/- 2.2 L, p < 0.0001). Residual creatinine clearance (p = 0.224) and residual urine output (p = 0.125) were similar and did not seem to influence the results. Compared with their LWS counterparts, members of the NWS group were more likely to have higher iron saturation (p = 0.053) and serum ferritin (p = 0.004), but lower achieved hemoglobin (p = 0.055).Successful PD is feasible in larger-weight individuals; however, given the retrospective nature of the present study, prospective trials are needed to confirm that observation. PMID- 28988593 TI - Corticosteroid-induced vaso-occlusive events may be prevented by lowering hemoglobin S levels in adults with sickle cell disease. PMID- 28988594 TI - The need for standardized evaluation and feedback processes for experiential placements worldwide. PMID- 28988595 TI - A Larger BAT Improves Metabolism but Whiffs on Safety. PMID- 28988596 TI - TNF-alpha/IL-10 ratio: An independent predictor for coronary artery disease in North Indian population. AB - BACKGROUND/AIM: Cytokines are responsible for the modulation of immunological and inflammatory processes and play a significant role in the pathogenesis of coronary artery disease (CAD). Tumor necrosis factor-alpha (TNF-alpha) are considered as a pro inflammatory and interleukin-10 (IL-10) anti inflammatory have been shown to predict the risk of incident of CAD. Aim of present study is to examine the impact of the TNF-alpha and Il-10 levels on various components of the CAD. METHODS: Total 580 subjects were recruited in the present study out of which 290 diagnosed CAD subjects (Age 51.61+/-9.26; BMI 25.27+/-3.58) and 290 healthy controls (Age 51.72+/-9.48; BMI 24.02+/-7.42). Serum TNF-alpha and IL-10 levels were measured by ELISA. RESULTS: Data of present study revealed that CAD patients had higher frequency (p=0.001) of smoking (38.28%), Alcohol (21.03%), Diabetes (53.45%) and hypertension (48.28%) as compare to controls. Moreover, we have observed highly significant (p<0.05) difference in PR, BMI, DBP, DBP, Glucose, TC, TG, VLDL, LDL, TNF-alpha and TNF-alpha/IL-10. However, HDL and IL-10 were found lower in CAD. CONCLUSION: The findings of present study suggest that the TNF-alpha/IL-10 ratio may play a vital role in the development of CAD of North Indian population. PMID- 28988598 TI - Nipple sparing mastectomy and microsurgical breast reconstruction: An approach for success. PMID- 28988597 TI - Dosing issues with non-vitamin K antagonist oral anticoagulants for the treatment of non-valvular atrial fibrillation: Why we should not underdose our patients. AB - Non-vitamin K antagonist oral anticoagulants (NOACs) - dabigatran, rivaroxaban, apixaban and edoxaban - are well established in terms of preventing stroke or systemic embolism in patients with non-valvular atrial fibrillation and high thromboembolism risk. When prescribed incorrectly, NOACs are associated with an increased risk of ischaemic events and bleeding. Current NOAC labels explicitly address dose adjustments according to age, body weight, renal function and concomitant treatment with P-glycoprotein inhibitors. The required dose adjustments vary significantly from molecule to molecule, thereby creating a complex dose adjustment environment. Furthermore, recommendations support assessment of individual risk using thromboembolic and bleeding risk scores. Evidence-based medicine also provides data about specific patient profiles. In particular, some patients who are at higher risk of bleeding, such as patients on polymedication, are often at higher risk of stroke. More and more patients are being treated with NOACs. The question of appropriate dosing has become important, as studies are starting to show that reduced doses are being prescribed at very high rates. Although these data have not been evaluated in light of individual risk assessments, in everyday practice, physicians are often more concerned about drug-related bleeding than about the spontaneous evolution of the disease (stroke/systemic embolism), leading to high rates of prescription of inadequately low doses. Recent results have shown that only certain risk criteria justify dose reduction. Thus, the right dose needs to be prescribed for the right patient in order to obtain, in real-life practice, the benefits of NOACs that have been demonstrated in randomized clinical trials. PMID- 28988599 TI - Pathological outcomes in men with prostate cancer who are eligible for active surveillance. AB - BACKGROUND: In order to prevent over treatment of prostate cancer and significant adverse effects after surgical intervention, active surveillance was suggested in low risk or very low risk patients. This study aimed to retrospectively analyze the adverse pathological results of candidates eligible for active surveillance. METHODS: A total of 904 patients underwent robot-assisted laparoscopic radical prostatectomy in this single institute, from 2005 to April 2014. One hundred and thirty-two patients were eligible for active surveillance (AS). Candidates for active surveillance were defined as low risk (T1/T2a, prostate specific antigen 10 ng/ml or less, and Gleason score 6 or less) and very low risk (T1c, prostate specific antigen density 0.15 or less, Gleason score 6 or less, 2 or fewer positive biopsy cores, 50% or less cancer involvement per core) patients. Adverse pathological results were defined as Gleason sum more than 6, and non-organ confined disease. RESULTS: There were 132 patients eligible for active surveillance. One hundred and thirteen (85.6%, 113/132) patients had low risk disease and nineteen (14.4%, 19/132) patients had very low risk disease. The adverse pathological results of low risk disease were upgrading Gleason sum and non-organ-confined disease, 41.6% (47/113) and 28.3% (32/113), respectively. The adverse pathological results of very low risk disease were upgrading Gleason sum and non-organ-confined disease, 15.8% (3/19) and 15.8% (3/19), respectively. CONCLUSION: We conclude that although AS may prevent over treatment and significant adverse effects after surgical intervention, stratification of patients with low risk prostate cancer is of paramount importance when choosing appropriate candidate for AS. The risk of adverse pathological results should be well informed in the pretreatment counseling. PMID- 28988600 TI - An evaluation study of reported pancreatic adenocarcinoma risk-associated SNPs from genome-wide association studies in Chinese population. AB - BACKGROUND: Previous genome-wide association studies (GWAS), and a pathway study of pancreatic ductal adenocarcinoma (PDAC) identified 14 significantly associated single nucleotide polymorphisms (SNPs) along with another 7 promising loci in European, Japanese, and Chinese descents. In this study, we aimed to evaluate the potential association of these SNPs with PDAC risk in the Chinese population. METHODS: In this Chinese population-based case-control study with 254 cases and 1200 controls, we tested 20 PDAC risk associated SNPs from previous GWAS and one SNP from a pathway-based study. RESULTS: All 21 SNPs were polymorphic in the Chinese population. Twenty SNPs were included in the final analysis after the quality check (QC). Among these SNPs, three were significantly associated with PDAC risk after Bonferroni correction (P < 2.5E-03) including rs7779540 (at 7q36.2, P = 3.89E-06, OR = 2.59, 95%CI: 1.73-3.87), rs10919791 (at 1q32.1, P = 6.07E-05, OR = 1.52, 95%CI: 1.24-1.86) and rs401681 (at 5p15.33, P = 5.15E-04, OR = 1.42, 95%CI: 1.17-1.73). Rs2255280 (at 5p13.1, P = 8.16E-03, OR = 1.31, 95%CI: 1.07-1.6) showed significant association at the p < 0.05 level. The directions of effect of these SNPs were consistent with previous studies. CONCLUSION: Four PDAC risk-associated SNPs identified in GWAS of various populations are associated with PDAC risk in the Chinese population. Information on PDAC risk-associated SNPs and their ORs may facilitate risk assessment of PDAC risk in the Chinese population. PMID- 28988601 TI - Colonization of the middle turbinate. PMID- 28988602 TI - A new hot spot for tick-borne encephalitis (TBE): A marked increase of TBE cases in France in 2016. AB - OBJECTIVES: Tick-borne encephalitis virus (TBEV) is a zoonotic agent causing severe encephalitis. In 2016, in Northeastern France, we faced a TBEV infection increase, leading to a warning from the Regional Health Agency. Here, we report the confirmed TBE cases diagnosed between January 2013 and December 2016, with particular emphasis on the year 2016. METHODS: A total of 1643 blood and cerebrospinal fluid (CSF) samples from everywhere in France, corresponding to 1460 patients, were prospectively tested for anti-TBEV-specific IgM and IgG antibodies by ELISA. Additional 39 blood and CSF samples from patients with suspected Lyme neuroborreliosis were retrospectively investigated. RESULTS: The TBEV seropositivity rate was estimated to 5.89% and 54 patients were diagnosed as TBE-confirmed cases. A significant increase in TBE cases was observed during the year 2016 with 29 confirmed cases, instead of a mean of eight cases during the three previous years (p=0.0006). Six imported cases and 48 autochthonous cases, located in the Alsace region (n=43) and in the Alpine region (n=5) were reported. Forty-six patients experienced neurological impairment. Nine patients showed an incomplete recovery at last follow-up (from 15days to eight months post infection). TBE diagnosis was performed earlier for patients taken in charge in the Alsace region than those hospitalized elsewhere in France (p=0.0087). Among the 39 patients with suspected Lyme neuroborreliosis retrospectively investigated, one showed a TBEV recent infection. CONCLUSION: The TBE increase that occurred in France in 2016 highlights the need to improve our knowledge about the true burden of TBEV infection and subsequent long-term outcomes. PMID- 28988603 TI - Exploring donor and product factors and their impact on red cell post-transfusion outcomes. AB - The impact of donor characteristics, red cell age, and red cell processing methods on recipient outcomes is an emerging area of research. Knowledge generated from exploring this transfusion continuum has the potential to change the way donors are selected and how donations are processed and stored with important clinical and operational impact. Recently, donor characteristics including age, gender, donation frequency, genetics, and ethnicity have been shown to affect product quality and possibly recipient outcomes. The structural, biochemical and immunological changes that occur with red cell storage appear to not cause harm to blood recipients after 14 randomized clinical trials. However, both in vitro and clinical data are now beginning to question the safety of blood stored for a shorter duration. Whole blood filtration, a method of blood processing, has been linked to inferior recipient outcomes when compared to red cell filtration. Collectively, this emerging body of literature suggests that pre transfusion parameters impact product quality and recipient outcomes and that no 2 units of red cells are quite the same. This review will summarize both the pre clinical and clinical studies evaluating these associations. PMID- 28988604 TI - Heart failure management with ambulatory pulmonary artery pressure monitoring. AB - Remote monitoring strategies have been developed to improve ambulatory care of heart failure patients and reduce heart failure hospitalizations. This article evaluates the CardioMEMS device, an implantable wireless pulmonary artery pressure monitor. We provide a historical review of remote monitoring in heart failure along with an in-depth analysis of the rationale, evidence, and limitations of the CardioMEMS device. PMID- 28988605 TI - Recovery of metal values from copper slag and reuse of residual secondary slag. AB - Resource and environmental factors have become major forces in mining and metallurgy sectors driving research for sustainability purposes. The concept of zero-waste processing has been gaining ground readily. The scant availability of high quality raw materials has forced the researchers to shift their focus to recycling while the exceedingly stringent environmental regulations have forced researchers to explore new frontiers of minimizing/eliminating waste generation. The present work is aimed at addressing both aspects by employing recycling to generate wealth from copper slag and producing utilizable materials at the same time thus restoring the ecosystem. Copper slag was characterized and processed. The pyro-metallurgical processing prospects to generate utilizable materials were arrived at through rigorous thermodynamic analysis. Carbothermal reduction at elevated temperature (near 1440 degrees C) helped recover a majority of the metal values (e.g., Fe, Cu and Mo) into the iron-rich alloy product which can be a feed material for steel making. On the other hand, the non-metallic residue, the secondary slag, can be used in the glass and ceramic industries. Reduction time and temperature and carbon content were shown to be the most important process variables for the reaction which were optimized to identify the most favored operating regime that maximizes the metal recovery and simultaneously maximizes the hardness of the secondary slag and minimizes its density, the two major criteria for the secondary slag product to be utilizable. The flux addition level was shown to have relatively less impact on the process performance if these are maintained at an adequate level. The work established that the copper slag, a waste material, can be successfully processed to generate reusable products through pyrometallurgical processing. PMID- 28988606 TI - A novel strategy for producing compost with enhanced biopesticide properties through solid-state fermentation of biowaste and inoculation with Bacillus thuringiensis. AB - In the framework of a circular economy, organic solid wastes are considered to be resources useful for obtaining value-added products. Among other potential uses, biodegradable wastes from agricultural, industrial, and domestic sources are being studied to obtain biopesticides through solid-state fermentation (SSF), mainly at the laboratory scale. The suitability of biowaste (source-selected organic fraction of municipal solid waste) for use as a substrate for Bacillus thuringiensis (Bt) growth under non-sterile conditions in a 10 L SSF reactor was determined in this study. An operational strategy for setting up a semi continuous process yielding a stabilised organic compost-like material enriched with Bt suitable for use as a soil amendment was developed. Concentrations of 1.7.107-2.2.107 and 1.3.107-2.1.107 CFU g-1 DM for Bt viable cells and spores, respectively, were obtained in the final material. As the results confirmed, Bt enriched compost-like material with potential biopesticide properties can be produced from non-sterile biowaste. PMID- 28988607 TI - Activity standardisation of 210Pb by 4pialpha liquid scintillation counting method. AB - The activity of 210Pb in a solution with 210Pb-210Po in the radioactive equilibrium was determined through its decay product 210Po by liquid scintillation counting (LSC), which has, after separation, as a pure alpha emitting nuclide, detection efficiency practically equal to 1. For the separation of 210Po from 210Pb solution, two methods based on precipitation of Pb, and Pb with Bi, leaving Po in the solution, were introduced. The first one was precipitation of Pb in the form of Pb(NO3)2 from a mixture of acetic acid, toluene, water and HNO3. The second one was based on co-precipitation of Bi and Pb with KCl from a mixture of organic solvents, where 210Bi with 210Pb was fixed to the precipitate. The relative standard uncertainty of 210Pb activity concentration was estimated to be lower than 0.45%. PMID- 28988608 TI - Routine C4d immunohistochemistry in cardiac allografts: Long-term outcomes. AB - BACKGROUND: In the past decade, C4d has emerged as a potential marker for antibody-mediated rejection (AMR); however, evidence on its use as a prognostic tool has been controversial. Although the International Society for Heart and Lung Transplantation guideline recommends early routine surveillance of C4d in heart transplantation, there is no consensus on its value in the pathologic assessment of AMR. Herein we present a correlation analysis of C4d immunoreactivity in endomyocardial biopsies with clinical cardiac dysfunction, cellular rejection, human leukocyte antigen (HLA) status, cardiac allograft vasculopathy (CAV) and death. METHODS: A total of 5,840 endomyocardial biopsies from 296 heart transplant recipients (January 2004 to December 2014) were stained prospectively for C4d. Strong, diffuse endothelial staining was considered positive. All patients had at least 1 year of follow-up. Positive C4d staining was present in 53 biopsies from 28 patients. Sixteen of 28 patients had clinically significant cardiac dysfunction at the time of positive biopsy. In C4d positive patients, the mean panel-reactive antibody (PRA) level was 33%. Ten patients demonstrated a first C4d positivity within the first year post transplant, whereas 18 patients had C4d positivity after 1 year post-transplant. At autopsy, all 11 C4d-positive patients examined demonstrated cardiac allograft vasculopathy (CAV) as the underlying cause of death. In contrast, only 2 of 8 (25%) C4d-negative patients had CAV at autopsy. In the surviving cohort, there was an angiographic diagnosis of higher-than-moderate CAV in 10 patients (3.8%). RESULTS: C4d-positive patients contributed to 67% of the overall institutional mortality in heart transplant recipients. Late C4d positivity (>1 year post transplant) demonstrated an even higher risk for developing CAV and poor prognosis than early C4d positivity (within 1 year). In the C4d-negative group with postmortem examination, 75% (6 of 8) deaths were due to non-cardiac causes. CONCLUSIONS: Our findings show a positive association of C4d with CAV and death. We identified a prognostic role for C4d in heart transplantation warranting routine long-term detection of this marker in the pathologic evaluation of cardiac AMR. PMID- 28988609 TI - Metformin and Abdominal Aortic Aneurysm. PMID- 28988610 TI - Trends and predictions to 2020 in breast cancer mortality in Europe. AB - OBJECTIVES: We analyzed trends in mortality from breast cancer in women in 36 European countries and the European Union (EU) over the period 1970-2014, and predicted numbers of deaths and rates to 2020. MATERIALS AND METHODS: We derived breast cancer death certification data and population figures from the World Health Organization and Eurostat databases. We obtained 2020 estimates using a joinpoint regression model. RESULTS: Overall, EU breast cancer mortality rates (world standard) declined from 17.9/100,000 in 2002 to 15.2 in 2012. The predicted 2020 rate is 13.4/100,000. The falls were largest in young women (20-49 years, -22% between 2002 and 2012). Within the EU, declines were larger in the United Kingdom (UK) and other northern and western European countries than in most central and eastern Europe. The UK has the second lowest predicted breast cancer mortality rate in 2020 (after Spain), starting from the highest one in 1970. Breast cancer mortality is predicted to rise in Poland, where the predicted 2020 rate is 15.3/100,000. We estimated that about 32,500 breast cancer deaths will be avoided in 2020 in the EU as compared to the peak rate of 1989, and a total of 475,000 breast cancer deaths over the period 1990-2020. CONCLUSION: The overall favourable breast cancer mortality trends are mainly due to a succession of improvements in the management and treatment of breast cancer, though early diagnosis and screening played a role, too. Improving breast cancer management in central and eastern Europe is a priority. PMID- 28988611 TI - Prevalence of Neurocognitive Dysfunction and Its Effects on Postoperative Outcomes in Total Joint Arthroplasty. AB - BACKGROUND: The prevalence of neurocognitive dysfunction (NCD) and its effects on postoperative outcomes have not been well characterized following total joint arthroplasty (TJA) population. This study aims at better understand this relationship. METHODS: Patients were evaluated for neurocognitive function using the grooved pegboard test for the dominant (PEG-D) and nondominant hand (PEG-N), and the Rey Auditory Verbal Learning Test (RAVLT). The patient scores for each test was compared to age-controlled normative values in order to identify NCD. Baseline characteristics and postoperative outcomes were then compared amongst the two cohorts. RESULTS: Ninety-nine consecutive patients were prospectively enrolled. Nearly 54% were identified as neurocognitively deficient on at least 1 of the 3 tests (31% by RAVLT, 21% by PEG-D, and 30% by PEG-N). There was a statistically significant prevalence of NCD in patients older than 60 years when compared to normative controls for RAVLT (P < .001). Patients with depression or an American Society of Anesthesiologist score of 3 were 5 times as likely to have NCD, while patients with a body mass index between 20-30 kg/m2 were 5 times less likely to have NCD. Furthermore, patients identified as NCD preoperatively were significantly more likely to be transferred to the intensive care unit (48% vs 14%) and fail physical therapy (64% vs 17%), respectively. CONCLUSION: NCD is highly prevalent within total joint arthroplasty candidates and may be correlated with higher body mass index, American Society of Anesthesiologist scores, and rates of depression. The condition predisposes patients to suboptimal postoperative outcomes including increased intensive care unit admissions and prolonged rehabilitation. PMID- 28988612 TI - Cost Analysis, Complications, and Discharge Disposition Associated With Simultaneous vs Staged Bilateral Total Knee Arthroplasty. AB - BACKGROUND: Simultaneous vs staged bilateral total knee arthroplasty (BTKA) has long been debated. The primary objective of this study was to compare actual hospital costs and complication rates in patients undergoing simultaneous BTKA (simBTKA) and staged BTKA (staBTKA) at a single institution. METHODS: A total joint arthroplasty database from a single hospital was used to identify all patients who underwent primary BTKA from 2013 to 2016 and divided into simultaneous and staged groups. StaBTKA patients were included if both procedures were performed within 1 year by the same surgeon. The combined total hospital cost of both procedures was used, and inpatient rehabilitation (IPR) costs were added for all patients discharged to IPR. RESULTS: There were 225 simBTKA and 337 staBTKA patients. SimBTKA patients were younger (61 +/- 8 vs 66 +/- 8 years, P < .001), had lower body mass index (31.3 +/- 5.9 vs 34.0 +/- 7.2, P < .001), were more predominately male (48% vs 38%, P = .029), and more likely to require IPR as compared with staBTKA patients. There was no difference in total hospital cost for simBTKA as compared with staBTKA ($24,596 +/- $5652 vs $24,915 +/- $5756, P = .586). Complications were more prevalent in the simBTKA group, including venous thromboembolism (5.4% vs 1.4%, P = .006) and blood transfusions (15.8% vs 6.2%, P < .001). CONCLUSION: There were higher complication rates with no significant cost savings in actual hospital costs associated with simBTKA, when accounting for the cost of IPR, as compared with staBTKA. The total cost analysis of simBTKA vs staBTKA, using actual cost data, merits further evaluation. PMID- 28988613 TI - Amelioration of panadol-induced nephrotoxicity via down-regulation of Bax/Bcl2 ratio with some antioxidants. AB - BACKGROUND: Overdoses of Panadol (APAP) result in hepatic and renal toxicity. Up till now, there is no effective drug for APAP-enhanced nephrotoxicity. This work aims to explore the protective effects of N-acetylcysteine, Thymoquinone (THQ), Curcumin (CUR) and alpha-Lipoic acid (LA) either alone or in combination against APAP nephrotoxicity, focused on modulation of Bax/Bcl2 pathway. METHODS: APAP was administrated at a single dose then treated with the fore mentioned antioxidants. RESULTS: APAP administration increased serum creatinine, urea, uric acid, tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta) levels compared to control group. There is a marked depletion of reduced glutathione (GSH) levels and superoxide dismutase activity (SOD), Bax level was overexpressed, whereas Bcl2 was downregulated in renal tissue. Histopathological examination of the kidney tissue supported these biochemical findings. Treatment with the fore mentioned anti-oxidants ameliorated most of the previous evaluated parameters and returned the kidney nearly to its normal architecture. CONCLUSION: The expression of Bax and Bcl2 is considered one of the mechanisms underlying APAP-induced nephrotoxicity. The administration of THQ along with CUR could be a promising antidote for APAP renal damage through their antioxidant potential. PMID- 28988614 TI - Neuroadaptive changes in metabotropic glutamate mGlu2/3R expression during different phases of cocaine addiction in rats. AB - BACKGROUND: In the cocaine addiction the development from transient into persistent neuroplastic changes strongly involves the glutamatergic system. In this respect, among glutamatergic receptors special attention is paid to the group II of metabotropic glutamatergic receptors (mGlu2/3R) which are involved in the transition from drug use to drug addiction including the relapse mechanisms. METHODS: The present study employed radioligand binding and Western blot assays to study mGlu2/3R density, affinity and protein expression in selected rat brain areas after cocaine self-administration, extinction training and cocaine-induced reinstatement. Rats were randomly assigned in triads to one of three conditions: contingent cocaine intravenous self-administration, non-contingent injections of cocaine (yoked cocaine), or saline yoked to the intake of the self-administering subject. RESULTS: Cocaine self-administration and yoked cocaine delivery resulted in a significant increase in the mGlu2/3R density in the prefrontal cortex and the dorsal striatum, while 10-day extinction training provoked a reduction in the prefrontal cortex and the nucleus accumbens. Cocaine abstinence also enhanced an increase in the [3H]ligand binding to mGlu2/3R in the prefrontal cortex. During reinstatement the cocaine challenge dose (10mg/kg, ip) led to important elevation in the mGlu2/3R density in the prefrontal cortex. CONCLUSIONS: Our study demonstrated the role of mGlu2/3R localized in the prefrontal cortex-striatum pathways to cocaine repeated exposure. PMID- 28988616 TI - Modified conventional bioreactor for microalgae cultivation. AB - Microalgae, a renewable source for third generation biofuel production, have a great potential if cultivated in high concentration economically. Bottleneck lies with designing economical and efficient photobioreactor. In addition, proportional C and N inputs in the known media does not support high specific growth rate and high biomass build-up. Nitrates in fermentation media, f/2 for Nannochloropsis sp. and Zarrouk's for Arthrospira platensis, were modified. Aeration and agitation were altered in conventional bioreactor (BIOFLO 110) to reduce power consumption, increase mixing time and prevents settling. This was achieved by introducing four way flow regime supporting uniform nutrient and cell distribution in media. Volumetric cell productivity for Nannochloropsis sp. and A. platensis were achieved as 0.618 g/l/d and 0.774 g/l/d, respectively. This photobioreactor also supported the maximum specific CO2 sequestration rates to the level of 0.42 g/g/h and 0.39 g/g/h for Nannochloropsis sp. and A. platensis, respectively, confirming efficient and effective operation. PMID- 28988617 TI - Translational Research - The Intersection Between Sociocultural and Environmental Factors and the Health of Children and Families. PMID- 28988615 TI - Mechanism of synergistic action on behavior, oxidative stress and inflammation following co-treatment with ketamine and different antidepressant classes. AB - BACKGROUND: Major depressive disorder (MDD) affects many people in the world. However, around 40% of patients do not respond to any pharmacological drugs. An alternative is to use a combination of different pharmacological groups or the combination of a classical antidepressant with a substance that can potentiate its effect. Thus, this study aimed to investigate the synergistic interactions between different antidepressants, including fluoxetine, quetiapine and lamotrigine in combination with ketamine, a N-methyl-d-aspartate (NMDA) receptor antagonist. METHODS: Wistar rats were acutely treated with fluoxetine (1.25mg/kg), quetiapine (5mg/kg), and lamotrigine (5.0mg/kg) alone or in combination with ketamine (5.0mg/kg), and then subjected to behavioral tests. In addition, oxidative damage and antioxidant capacity were assessed in the rat brain, and pro-inflammatory cytokines levels were evaluated in the serum. RESULTS: It was observed a synergistic effect of ketamine in combination with fluoxetine on the immobility time in the forced swimming test, indicating an antidepressant effect. Other antidepressant did not show effects when administrated alone or joint to ketamine. The combination of ketamine with other antidepressants, particularly quetiapine, in some brain regions induced an increase in damage to lipids and proteins. However, the combination of ketamine with fluoxetine increased the antioxidant activity of superoxide dismutase, and decreased oxidative damage, thus suggesting a neuroprotective effect of the combination of these drugs. The combination of ketamine with fluoxetine or lamotrigine reduced pro-inflammatory cytokines levels. CONCLUSION: In conclusion, ketamine induced antioxidant or pro-antioxidant effects dependent of antidepressant classes or brain area. PMID- 28988618 TI - Hospital burden of long-term genitourinary and gastrointestinal toxicity after radical radiotherapy for prostate cancer. AB - INTRODUCTION: Treatment options for prostate cancer (PCa) include radical radiotherapy (RT) and radical prostatectomy, both of which have comparable oncological outcomes. The aim of this study was to investigate the hospital burden of long-term genitourinary and gastrointestinal toxicity among patients with PCa who were treated with radiotherapy at our institution. METHODS: The radiotherapy department database was used retrospectively to identify all patients who underwent radiotherapy for PCa from January 2006 to January 2008. The patient administration system from each public hospital in the region was interrogated and all patient points of contact were recorded. Minimum follow up was 5 years. Individual patient charts were reviewed and factors that might influence outcomes were documented. RESULTS: We identified 112 patients. The mean age at diagnosis was 66 (44-76) and the median PSA was 12.1 (3.2-38). The mean duration of follow-up was 7.8 yrs. Twenty-three patients (20%) presented to the Emergency Department (ED) with late onset toxicity. Nine patients had more than 2 ED attendances. Twenty-five patients (22%) were investigated for genitourinary toxicity. Forty-seven patients (42%) underwent investigation for gastrointestinal side-effects and 45% of these required argon therapy (21/47). CONCLUSION: We found a significant hospital burden related to the management of gastrointestinal and genitourinary toxicity post radical radiotherapy for prostate cancer. As health care reforms gain momentum, policy makers must take into account the considerable longitudinal health care cost related to radiotherapy. It is also important that patients are counselled carefully in relation to potential long term side-effects. PMID- 28988619 TI - Bacterial Subversion of COG-Dependent Membrane Traffic. AB - Intracellular bacterial pathogens thrive within eukaryotic cells by interacting with a range of organelles to establish a replicative niche. In a new study in Cell Host and Microbe, Miller et al. identify a Brucella abortus effector that subverts membrane and protein transport to the Golgi apparatus to promote bacterial replication. PMID- 28988620 TI - Collapsing the Metabolic PON2zi Scheme in Pancreatic Ductal Adenocarcinoma. AB - A hallmark of pancreatic ductal adenocarcinoma cancer (PDAC) cells is metabolic reprogramming that facilitates tumor progression. In a recent paper published in Molecular Cell, Nagarajan et al. discover that paraoxonase (PON)2 stimulates glucose transporter (GLUT)1-mediated glucose uptake, prevents AMP-activated protein kinase (AMPK)-mediated anoikis, and consequently promotes PDAC development and metastasis. PMID- 28988621 TI - Oxidation of M252 but not M428 in hu-IgG1 is responsible for decreased binding to and activation of hu-FcgammaRIIa (His131). AB - Oxidation of monoclonal therapeutic antibodies (mAbs) can affect binding to Fc receptors and potentially influence pharmacokinetics or effector functions like e.g. antibody dependent cellular phagocytosis (ADCP). Recently, it has been demonstrated that binding to FcgammaRIIa (H131) is affected by methionine oxidation of the Fc-portion but it is currently unknown which methionine is responsible for decreased binding. We separated an oxidized IgG1 monoclonal antibody based on the oxidation state of methionine 252 and analyzed fractionated material in receptor binding experiments as well as in functional (cell-based) assays. Although the unfractionated mixture demonstrated weaker interaction/activation of the receptor, differently oxidized isolated subspecies can lead both to stronger as well as weaker binding and activation of the histidine variant of FcgammaRIIa. PMID- 28988622 TI - Back to the future of targeting leukotriene B4 mediated inflammation. PMID- 28988623 TI - Stakeholder perceptions of lowering the blood alcohol concentration standard in the United States. AB - PURPOSE: This study sought to better understand the past change in the legal blood alcohol concentration (BAC) standard from 0.10% to 0.08% in the United States, as well as explore stakeholder perceptions about potential health and other impacts of further lowering the standard below 0.08%. METHODS: In-depth interviews were conducted with representatives of 20 organizations considered to have an interest and investment in the potential impacts of strategies to decrease alcohol-impaired related crashes and injuries. Interviews were conducted by a trained moderator, using a structured guide. RESULTS: Themes from the interviews are presented for several discussion topics explored for both the earlier change in the legal BAC limit from 0.10% to 0.08% and a potential lowering of the limit below 0.08%. Topics included arguments for and against change; organizational position on the change; stakeholders on both sides of the issue; strategies to support or oppose the change; health and economic impacts; and enforcement and adjudication challenges. CONCLUSIONS: Collectively, results suggest that moving the BAC standard below the current level will require considerable effort and time. There was strong, but not complete, agreement that it will be difficult, and maybe infeasible in the short-term, for states to implement a BAC standard lower than 0.08%. PMID- 28988624 TI - Recently reported biological activities of pyrazole compounds. AB - The pyrazole nucleus is an aromatic azole heterocycle with two adjacent nitrogen atoms. Pyrazole derivatives have exhibited a broad spectrum of biological activities, and approved pyrazole-containing drugs include celecoxib, antipyrine, phenylbutazone, rimonabant, and dipyrone. Many research groups have synthesized and evaluated pyrazoles against several biological agents. This review examines recent publications relating the structures of pyrazoles with their corresponding biological activities. PMID- 28988625 TI - In vivo programming of endogenous antibodies via oral administration of adaptor ligands. AB - Vaccination is a reliable method of prophylaxis and a crucial measure for public health. However, the majority of vaccines cannot be administered orally due to their degradation in the harsh gut environment or inability to cross the GI tract. In this study, we report the first proof-of-concept study of orally producible chemically programmed antibodies via specific conjugation of adaptor ligands to endogenous antibodies, in vivo. Pre-immuniztion with 2,4-dinitrophenyl (DNP), or the reactive hapten, 1,3-diketone (DK), or a novel reactive hapten, vinyl sulfone (VS) in mice, followed by oral administration of adaptor ligands composed of the hapten and biotin to the pre-immunized mice resulted in successful in vivo formation of the biotin-hapten-antibody complexes within 2h. Pharmacokinetic evaluations revealed that apparent serum concentrations of programmed antibodies were up to 144nM and that the serum half-lives reached up to 34.4h. These findings show promise for the future development of orally bioavailable drug-hapten-antibody complexes asa strategy to quickly and easily modulate immune targets for aggressive pathogens as well as cancer. PMID- 28988626 TI - Synthesis and structure activity relationships of carbamimidoylcarbamate derivatives as novel vascular adhesion protein-1 inhibitors. AB - Vascular adhesion protein-1 (VAP-1) is a promising therapeutic target for the treatment of diabetic nephropathy. Here, we conducted structural optimization of the glycine amide derivative 1, which we previously reported as a novel VAP-1 inhibitor, to improve stability in dog and monkey plasma, and aqueous solubility. By chemical modification of the right part in the glycine amide derivative, we identified the carbamimidoylcarbamate derivative 20c, which showed stability in dog and monkey plasma while maintaining VAP-1 inhibitory activity. We also found that conversion of the pyrimidine ring in 20c into saturated rings was effective for improving aqueous solubility. This led to the identification of 28a and 35 as moderate VAP-1 inhibitors with excellent aqueous solubility. Further optimization led to the identification of 2-fluoro-3-{3-[(6-methylpyridin-3-yl)oxy]azetidin-1 yl}benzyl carbamimidoylcarbamate (40b), which showed similar human VAP-1 inhibitory activity to 1 with improved aqueous solubility. 40b showed more potent ex vivo efficacy than 1, with rat plasma VAP-1 inhibitory activity of 92% at 1h after oral administration at 0.3mg/kg. In our pharmacokinetic study, 40b showed good oral bioavailability in rats, dogs, and monkeys, which may be due to its improved stability in dog and monkey plasma. PMID- 28988628 TI - Challenges in the design of insulin and relaxin/insulin-like peptide mimetics. AB - Peptidomimetics are designed to overcome the poor pharmacokinetics and pharmacodynamics associated with the native peptide or protein on which they are based. The design of peptidomimetics starts from developing structure-activity relationships of the native ligand-target pair that identify the key residues that are responsible for the biological effect of the native peptide or protein. Then minimization of the structure and introduction of constraints are applied to create the core active site that can interact with the target with high affinity and selectivity. Developing peptidomimetics is not trivial and often challenging, particularly when peptides' interaction mechanism with their target is complex. This review will discuss the challenges of developing peptidomimetics of therapeutically important insulin superfamily peptides, particularly those which have two chains (A and B) and three disulfide bonds and whose receptors are known, namely insulin, H2 relaxin, H3 relaxin, INSL3 and INSL5. PMID- 28988627 TI - Design, synthesis, and evaluation of salicyladimine derivatives as multitarget directed ligands against Alzheimer's disease. AB - A series of salicyladimine derivatives were designed, synthesized and evaluated as multi-target-directed ligands for the treatment of Alzheimer's disease (AD). Biological activity results demonstrated that some derivatives possessed significant inhibitory activities against amyloid-beta (Abeta) aggregation and human monoamine oxidase B (hMAO-B) as well as remarkable antioxidant effects and low cell toxicity. The optimal compound, 5, exhibited excellent potency for inhibition of self-induced Abeta1-42 aggregation (91.3+/-2.1%, 25MUM), inhibition of hMAO-B (IC50, 1.73+/-0.39MUM), antioxidant effects (43.4+/-2.6MUM of IC50 by DPPH method, 0.67+/-0.06 trolox equivalent by ABTS method), metal chelation and BBB penetration. Furthermore, compound 5 had neuroprotective effects against ROS generation, H2O2-induced apoptosis, 6-OHDA-induced cell injury, and a significant in vitro anti-inflammatory activity. Collectively, these findings highlighted that compound 5 was a potential balanced multifunctional neuroprotective agent for the development of anti-AD drugs. PMID- 28988629 TI - Design and synthesis of a novel series of orally active, selective somatostatin receptor 2 agonists for the treatment of type 2 diabetes. AB - The discovery of a novel series of beta-methyltryptophan (beta MeTrp) derivatives as selective and orally active non-peptide somatostatin receptor 2 (SSTR2) agonists for the treatment of Type 2 diabetes is described. In our previous research, Compound A, beta-MeTrp derivative with highly potent and selective SSTR2 agonistic activity IC50 (SSTR2/SSTR5)=0.3/>100 (nM), was identified asa drug candidate for treatment of Type 2 diabetes which lowers significantly plasma glucose level in Wistar fatty rats in its oral administrations. However, as serious increase in AUC and phospholipidosis (PLsis) were observed in its toxicological studies in rats, follow-up compounds were searched to avoid risk of PLsis with reference to their in vitro PLsis potentials evaluated on the basis of accumulation of phospholipids in HepG2 cells exposed to the compounds. It has been found that introduction of a carbonyl group onto the piperidine and piperazine or aniline moiety of compounds A and B reduced markedly the in vitro PLsis potentials. And further modification of the compounds and their evaluation led to a discovery of compounds 3k with lower in vitro PLsis potentials exhibiting lowering effect of hypoglycemia-induced glucagon secretion in SD rats (ED50=1.1mg/kg) and glucose excursion in meal tolerance test in Wistar fatty diabetic rats (MED=3.0mg/kg) in oral administrations. Compound 3k was selected asa new drug candidate of selective and orally active non-peptide SSTR2 agonists for treatment of Type 2 diabetes with low in vivo PLsis potential. PMID- 28988630 TI - Differences in short-term clinical and radiological outcomes depending on timing of balloon kyphoplasty for painful osteoporotic vertebral fracture. AB - BACKGROUND: Balloon kyphoplasty or vertebroplasty is widely performed as a surgical intervention for osteoporotic vertebral fracture (OVF) and the effects have been investigated in many previous studies. However, the influence of the timing of the procedure on patient outcomes has not been studied formally. The purpose of this study was to investigate differences in the surgical outcomes of OVFs according to the timing of balloon kyphoplasty. METHODS: This was a multicenter cohort study. Participants comprised 72 consecutive patients who underwent balloon kyphoplasty between January 2012 and January 2016. Patients were analyzed in two groups according to the timing of kyphoplasty after onset (Early group: <=2 months; Late group: >2 months). Follow-up continued for more than 6 months. RESULTS: A total of 72 patients were effectively analyzed. Of these, 27 (38%) patients underwent kyphoplasty within 2 months after symptom onset. The Late group showed greater angular motion of fractured vertebrae (p = 0.005) and compression of anterior vertebral height (p = 0.001) before surgery. Final outcomes adjusted for age and preoperative outcome showed lower visual analog scale (VAS) scores for low back pain in the Early group than in the Late group (19.9 vs. 30.4, p = 0.049). Final relative anterior vertebral height and kyphotic angle were more preserved in the Early group than in the Late group (p = 0.002 and p = 0.020, respectively), although absolute differences were not significant. CONCLUSIONS: Vertebral height and kyphotic angle before and after balloon kyphoplasty were greater in patients who underwent kyphoplasty within 2 months after onset, and the VAS score for low back pain at final follow-up was better. Our results support kyphoplasty within 2 months. PMID- 28988631 TI - Necessity of D2 lymph node dissection in older patients >=80years with gastric cancer. AB - OBJECTIVES: This study analyzed the effect of D2 lymph node (LN) dissection on complications and survival in older patients with gastric cancer. MATERIALS AND METHODS: A total of 103 octogenarian patients who underwent curative gastrectomy for gastric cancer were divided into two groups (D2 and D1) according to the extent of LN dissection and analyzed retrospectively for complications and survival. RESULTS: No differences were observed in short-term postoperative outcomes, including complication rates, between the two groups. In a survival analysis, D2 LN dissection did not improve overall survival (OS) in any patient, including advanced cases. A Cox regression analysis revealed that the independent risk factors for OS were history of coronary artery disease (hazard ratio [HR], 11.095), postoperative short-term complications (HR, 9.939), and TNM stage (HR, 6.299). The extent of LN dissection was not an independent risk factor for OS, and D2 or more LN dissection (odds ratio, 10.89) increased the risk independently. CONCLUSIONS: D2 or more LN dissection did not improve survival, but rather increased the risk of complications. Thus, LN dissection should be performed sparingly in octogenarian patients with gastric cancer. PMID- 28988632 TI - Leisure time physical activity patterns in Odisha, India. AB - AIMS: The World Health Organization has recommended a moderate intensity physical activity of 150min, or 75min vigorous-intensity physical activity per week to achieve optimal health benefits. It is not known if Indian populations who indulge in leisure time physical exercises satisfy these recommendations. METHODS: This study used a questionnaire to obtain data regarding demographic details, current engagement in leisure time physical activities, and dosages of these exercises from participants between 18 and 64 years of age. RESULTS: Data was collected from a total of 390 participants (231 males and 159 females). 50.76% and 34.35% of the participants reported exercising voluntarily and for health benefits respectively. Most participants (94.61%) indicated exercising without prescription. 55.38% and 12.82% of the participants under and above 38 years of age perform moderate to vigorous intensity exercises respectively. CONCLUSION: The over-all results of this study indicate that the participants' choices of leisure time physical exercises are based on their personal choices and beliefs. The exercise intensities undertaken do not meet the global recommended intensities, especially in those above 38 years of age. Professionals and facilities to engage the public in the WHO recommended intensities of physical activity needs to be established. PMID- 28988633 TI - Stabilizing the Transcription Factors by E3 Ligase COP1. AB - Photomorphogenesis is oppositely regulated by two groups of transcription factors. CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1) degrades the positive factors but stabilizes the negative ones to predominantly repress photomorphogenesis. It is known that COP1 degrades substrates as an E3 ligase. Two recent studies unraveled the long-sought mechanisms of how COP1 stabilizes the negative transcription factors. PMID- 28988634 TI - A Two-Tiered Strategy for Preventing Complications of Bereavement in the First Thirteen Months Post-Loss: A Pilot Study Using Peer Supports with Professional Therapist Back-up. AB - This feasibility and acceptance pilot study for preventing complications of bereavement within the first year post loss recruited 20 adult grievers within 9 months of becoming bereft and assigned consenting subjects to peer supporters trained by a non-profit bereavement support organization for weekly or bi-weekly telephone-based peer support until month 13 post-loss. Subjects who met DSM-5 criteria for major depressive disorder or showed an Inventory of Complicated Grief (ICG) score exceeding 19, 6 months or more post loss, were assigned to 12 to 16 weeks of interpersonal psychotherapy (IPT) with an experienced therapist. Eight and six subjects completed the protocol assigned to peer support and IPT, respectively, with pre/post Patient Health Questionnaire-9 scores of 5.38 (2.45) versus 3.25 (4.13) (p = 0.266) and 16.67 (7.17) versus 8.40 (5.73) (p =0.063); and pre/post ICG scores of 12.50 (4.72) versus 5.00 (2.51) (p = 0.016) and 35.17 (5.12) versus 8.4 (5.73) (p = 0.063). Implications of this two-tiered model of early intervention for preventing complications of grief are discussed. PMID- 28988635 TI - [Pediatricians and accompanied or unaccompanied foreign minors]. PMID- 28988636 TI - [Maternal anxiety related to how the pediatrician provided prenatal information about preterm birth]. AB - INTRODUCTION: Women hospitalized for preterm labor require clear information about prematurity. This study assessed whether or not specific written information about prematurity delivered at admission to the unit combined with an oral explanation from a pediatrician would decrease women's anxiety compared to an oral explanation alone. MATERIAL AND METHODS: This was a prospective, single center observational study. Women were included in the high-risk pregnancies department and distributed into two groups: receiving "only oral" information for a prenatal clinical consultation with a senior pediatrician or receiving "combined" oral information+a booklet about prematurity given to the women at admission. The primary endpoint was the change in anxiety-state (before and after the information procedure) evaluated by the State Trait Anxiety Inventory-Y (STAI Y). RESULTS: The anxiety score before receiving information did not differ between the two groups (STAI-Y-A "combined" group: 46.7+/-3.0 vs. "only oral" group: 42.7+/-2.74; P=0.55). After consultation with a pediatrician, the acute anxiety-state score STAI-Y-A decreased significantly in the "combined" group ( 6.7+/-1.9) compared to the "only oral" group (-2.5+/-4.6; P<0.05). DISCUSSION: A booklet about prematurity combined with oral information from a pediatrician reduced patients' anxiety more than oral information alone. Given that the psychology of the mother interacts with the pregnancy, it is necessary to provide clear and adapted information. Giving a booklet appears to be one of the modalities to improve information. Other modalities such as video documents have to be studied. PMID- 28988637 TI - [Value of procalcitonin for infants with bronchiolitis in an emergency department]. AB - CONTEXT: Very few studies have evaluated the role of procalcitonin (PCT) in infants with bronchiolitis. AIMS: To describe infants who had both a diagnosis of bronchiolitis at the emergency department and a blood test including PCT, and to compare the characteristics of children according to the PCT value. METHODS: Infants admitted to the Pediatric Emergency Department between 1 January 2014 and 31 December 2014 who had a diagnosis of bronchiolitis and a blood test including PCT were included. The clinical, biological, and radiological characteristics of the infants with PCT <1 or >=1g/L were compared. RESULTS: One hundred thirty six infants were included. Patients with high PCT (n=20) had a higher temperature (38.5 degrees C, IQR=37.8-38.6 vs. 37.5 degrees C, IQR=37.1-38.2; P<0.01), C reactive protein (50mg/L, IQR=25-83 vs. 5mg/L, IQR=0-19; P<0.01), and neutrophils (7.8*109/L, IQR=6.0-8.5 vs 4.5*109/L, IQR=2.9-6.6; P<0.01) higher than patients with low PCT (n=116). Presence on the chest x-ray of alveolar condensation did not differ between the two PCT groups. Infants coming from the low-PCT group received fewer antibiotics (14.7% vs 65%; P<0.01). CONCLUSION: In a Pediatric Emergency Department, PCT with a value of 1 or more cannot predict the presence of alveolar condensation on the chest x-ray. It seems to be associated with the antibiotics prescription, even if this could not be proved because of the design of the study. PMID- 28988638 TI - [Pseudotumoral genital schistosomiasis]. PMID- 28988639 TI - Can we keep the MD program within reach of OMS? PMID- 28988640 TI - Signaling pathway impact analysis by incorporating the importance and specificity of genes (SPIA-IS). AB - rlying biology of differentially expressed genes and proteins. Although various approaches have been proposed to identify cancer-related pathways, most of them only partially consider the influence of those differentially expressed genes, such as the gene numbers, their perturbation in the signaling transduction, and the interaction between genes. Signaling-pathway impact analysis (SPIA) provides a convenient framework which considers both the classical enrichment analysis and the actual perturbation on a given pathway. In this study, we extended previous proposed SPIA by incorporating the importance and specificity of genes (SPIA-IS). We applied this approach to six datasets for colorectal cancer, lung cancer, and pancreatic cancer. Results from these datasets showed that the proposed SPIA-IS could effectively improve the performance of the original SPIA in identifying cancer-related pathways. PMID- 28988641 TI - Sex-dependent effects of diabetes mellitus on the revascularization rate in mid term follow up of young patients with coronary artery disease. AB - AIMS: We investigated the association between Type-2 diabetes mellitus (DM) and the need for revascularization at a 5-year follow-up of young coronary artery disease patients and the role of sex in this regard. METHODS: Among 1121 young (males<=45, and females<=55years) patients (female: 49.7%) from Tehran Heart Center's Premature Coronary Atherosclerosis Cohort, 371(33.1%) had diabetes prior to angiography. Revascularization was considered as either percutaneous coronary intervention or coronary artery bypass graft surgery. RESULTS: The mean follow-up duration was 57.67+/-22.43months. In the univariable analysis, diabetics were at a significantly higher risk of revascularization than nondiabetics (Sub distributional Hazard Ratio [SHR]=1.843, P value<0.001). There was no association between DM and revascularization among men (SHR=1.232, P value=0.508). In contrast, women with DM had threefold more revascularization risk than women without DM (SHR=3.519, P value<0.001). After adjustment for confounding factors, the risk of revascularization in diabetics compared to nondiabetics increased to 2.139 fold (95% CI=1.473, 3.108) among the whole subjects, remained nonsignificant among men, and increased significantly to 3.725 fold (95% CI=2.067, 6.725) in women. CONCLUSIONS: Our data showed that in women with premature CAD, but not in men, DM may have a significant role in emerging revascularization during a mean follow-up of 5years. PMID- 28988642 TI - Risk of beta-cell autoimmunity presence for progression to type 1 diabetes: A systematic review and meta-analysis. AB - BACKGROUND: Islet autoantibodies have been applied for diagnosis of type 1 diabetes mellitus (T1DM) at an asymptomatic stage in individuals with high-risk genotypes. Evidence is insufficient to support a broad application of islet autoantibody screening for T1DM in clinical practice. The aim of this study was to assess the evidence of an association between islet autoantibodies and the development of T1DM in a pooled population of both genetically at-risk individuals and general people without definite genetic background. METHODS: A comprehensive literature search was performed of Pubmed, Web of knowledge and Cochrane library. Prospective cohort studies evaluating the role of islet autoantibodies in prediction of T1DM progression were included. Risk ratios (RRs) were calculated and pooled to arrive at summary estimate. chi2 and I2-values were calculated as measures of heterogeneity and subgroup analyses were performed to explore sources of heterogeneity. RESULTS: Twenty-one studies matched the inclusion criteria. A total of 71,482 nondiabetic participants who were genetically at-risk individuals or from the general population were included, and 926 cases of T1DM were reported during a median follow-up of 7 years. Compared with people free of islet autoantibody, those positive for any type or number of islet autoantibody showed a significantly increased risk of developing T1DM (RR 150.42 [95% CI 87.34, 259.04]). Moreover, the risk for people with multiple islet autoantibodies was 8.59-fold higher than the risk for those with single islet autoantibody, although a moderate heterogeneity existed between studies. The subgroup analysis further revealed that RRs of multiple islet autoantibodies in at-risk population and general population were 7.17 and 13.72, respectively. CONCLUSION: This study established the association between the seroconversion of islet autoantibodies and T1DM progression in nondiabetic people with or without definite genetic susceptibility, providing further evidence for an extensive application in routine clinical practice to identify individuals at risk of T1DM. PMID- 28988643 TI - A novel fitting algorithm for alignment curve radius estimation using corneal elevation data in orthokeratology lens trial. AB - PURPOSE: To evaluate a novel fitting algorithm for estimation of alignment curve (AC) radius during orthokeratology lens trial. METHODS: Fifty myopic children were recruited in this study. AC radii were estimated by both traditional method using flat K readings and eccentricity values and by a novel fitting algorithm, which was composed of 256 circle fittings using corneal elevation data from the corresponding AC region and a succedent toric fitting based on these calculated AC curvatures. Parameters of the final ordered lenses were determined by fluorescein analysis and corneal topography. The number of lens trials was recorded for each patient, and the consistencies of AC radius and astigmatism between the first trial lenses and the final ordered lenses were tested by Pearson correlations and Bland-Altman plots. RESULTS: The numbers of trials for the novel algorithm and traditional method were 1.2+/-0.4 times vs. 1.8+/-0.7 times, respectively, and Mann-Whitney test showed significant difference (z= 3.27, p=0.001). AC radii of the first trial lenses estimated by the novel fitting algorithm were more close to that of the final ordered lenses, showing a R square value of 0.994 for the fitting algorithm and 0.927 for the traditional method, respectively. Similar results could also be noticed for astigmatism estimation. CONCLUSION: AC radius and astigmatism of ortho-k lens could be better estimated by two steps of fitting algorithm using corneal elevation data, which may shorten the time needed for ortho-k lens trial and achieve better lens fitting status. PMID- 28988644 TI - Longitudinal study of accelerated long-term forgetting in children with genetic generalized epilepsy: Evidence of ongoing deficits. AB - Accelerated long-term forgetting (ALF) is a recently described memory disorder characterised by adequate recall after short, but not long delays. Currently, the prevailing conceptualisation of ALF is of a seizure related phenomenon. The main aim of this study was to assess whether ALF subsides as epilepsy severity and seizures abate in children with genetic generalized epilepsy (GGE). Eighteen children with GGE were compared over time to 29 healthy controls on a range of cognitive measures. The primary outcome was a modified version of the California Verbal Learning Test for Children with a long delay (seven day) recall component. At approximately two years follow up, ALF was apparent, although epilepsy severity subsided and seizures resolved in many children. This result contrasts with the dominant conceptualisation of ALF being a seizure related phenomenon. Moreover, at follow-up, worse recall at the long delay was related to greater epilepsy severity at baseline and earlier age of seizure onset, but not to being seizure free at follow-up. While at follow-up worse recall at the long delay related to the worse baseline recall at the long delay, this recall did not relate to scores obtained on standardised memory tests at baseline. Our study suggests that ALF may not be seizure related and identifies factors associated with risk of ALF in children with GGE. PMID- 28988645 TI - PD-1 inhibition in bone sarcoma and soft-tissue sarcoma. PMID- 28988647 TI - Secondary prevention of cervical cancer. AB - Cervical cancer affects women in their reproductive ages. Screening is an important secondary prevention strategy. The long process of carcinogenic transformation from human papillomavirus (HPV) infection to invasive cancer provides ample opportunities to detect the disease at a stage when treatment is highly effective. Suitable screening tests are cytology, visual inspection after acetic acid application and HPV detection tests. Evidence of effectiveness of the tests to reduce cervical cancer mortality and the cost-effectiveness of screening programs have been demonstrated. Cervical intraepithelial neoplasia grade 2 and grade 3 are the high-grade cervical cancer precursors and need to be treated. Treatment is safe and effective with ablative or excisional techniques. The World Health Organization recommends screening women at least once in a lifetime between 30 and 49 years of age and ensuring effective treatment of the detected abnormalities. Combination of HPV vaccination and population-based screening will be instrumental in eliminating cervical cancer. PMID- 28988646 TI - Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial. AB - BACKGROUND: Patients with advanced sarcomas have a poor prognosis and few treatment options that improve overall survival. Chemotherapy and targeted therapies offer short-lived disease control. We assessed pembrolizumab, an anti PD-1 antibody, for safety and activity in patients with advanced soft-tissue sarcoma or bone sarcoma. METHODS: In this two-cohort, single-arm, open-label, phase 2 study, we enrolled patients with soft-tissue sarcoma or bone sarcoma from 12 academic centres in the USA that were members of the Sarcoma Alliance for Research through Collaboration (SARC). Patients with soft-tissue sarcoma had to be aged 18 years or older to enrol; patients with bone sarcoma could enrol if they were aged 12 years or older. Patients had histological evidence of metastatic or surgically unresectable locally advanced sarcoma, had received up to three previous lines of systemic anticancer therapy, had at least one measurable lesion according to the Response Evaluation Criteria In Solid Tumors version 1.1, and had at least one lesion accessible for biopsy. All patients were treated with 200 mg intravenous pembrolizumab every 3 weeks. The primary endpoint was investigator-assessed objective response. Patients who received at least one dose of pembrolizumab were included in the safety analysis and patients who progressed or reached at least one scan assessment were included in the activity analysis. Accrual is ongoing in some disease cohorts. This trial is registered with ClinicalTrials.gov, number NCT02301039. FINDINGS: Between March 13, 2015, and Feb 18, 2016, we enrolled 86 patients, 84 of whom received pembrolizumab (42 in each disease cohort) and 80 of whom were evaluable for response (40 in each disease cohort). Median follow-up was 17.8 months (IQR 12.3-19.3). Seven (18%) of 40 patients with soft-tissue sarcoma had an objective response, including four (40%) of ten patients with undifferentiated pleomorphic sarcoma, two (20%) of ten patients with liposarcoma, and one (10%) of ten patients with synovial sarcoma. No patients with leiomyosarcoma (n=10) had an objective response. Two (5%) of 40 patients with bone sarcoma had an objective response, including one (5%) of 22 patients with osteosarcoma and one (20%) of five patients with chondrosarcoma. None of the 13 patients with Ewing's sarcoma had an objective response. The most frequent grade 3 or worse adverse events were anaemia (six [14%]), decreased lymphocyte count (five [12%]), prolonged activated partial thromboplastin time (four [10%]), and decreased platelet count (three [7%]) in the bone sarcoma group, and anaemia, decreased lymphocyte count, and prolonged activated partial thromboplastin time in the soft-tissue sarcoma group (three [7%] each). Nine (11%) patients (five [12%] in the bone sarcoma group and four [10%] in the soft tissue sarcoma group) had treatment-emergent serious adverse events (SAEs), five of whom had immune-related SAEs, including two with adrenal insufficiency, two with pneumonitis, and one with nephritis. INTERPRETATION: The primary endpoint of overall response was not met for either cohort. However, pembrolizumab showed encouraging activity in patients with undifferentiated pleomorphic sarcoma or dedifferentiated liposarcoma. Enrolment to expanded cohorts of those subtypes is ongoing to confirm and characterise the activity of pembrolizumab. FUNDING: Merck, SARC, Sarcoma Foundation of America, QuadW Foundation, Pittsburgh Cure Sarcoma, and Ewan McGregor. PMID- 28988648 TI - BAT Expansion: A Panacea against Obesity? Lessons from LKB1. PMID- 28988649 TI - Dry facts are not always inviting: a content analysis of Korean videos regarding Parkinson's disease on YouTube. AB - This study aimed to evaluate the accuracy of Korean videos regarding Parkinson's disease (PD) on YouTube and viewers' responses to them. YouTube search was performed using the search term "Parkinson disease" in Korean language on March 28, 2017. Two independent neurologists categorized the videos into "reliable", "misleading" or "patient experiences". The number of views, days since upload, video length, number of "likes" and "dislikes", and upload source were collected for each video. A total of 138 videos were included in this study. Of these, 91 videos (65.9%) were reliable; 31 (22.5%) were misleading, and 16 (11.6%) were of patient experiences. The videos with patient experiences had the highest number of mean views with 9710.4+/-3686.9, followed by misleading videos with 5075.0+/ 1198.6, and reliable videos with 2146.8+/-353.4 (ANOVA, p<0.001). The number of mean views per day was 4.0+/-0.6 for the reliable videos, which was significantly lower than the misleading videos (9.7+/-3.4, p=0.020) and the videos of patient experiences (11.3+/-4.6, p=0.023). The reliable videos were mostly uploaded by university hospitals (46.2%) and misleading videos by health-related commercial entities (74.2%). The misleading videos as well as the videos of patient experiences advocated "diet" asa treatment of PD. The current study found that only two-thirds of the Korean videos regarding PD on YouTube provide reliable information. More importantly, the videos with reliable contents were less popular than videos with misleading contents. Further efforts are warranted to effectively increase the dissemination of accurate and scientifically proven PD information to YouTube users. PMID- 28988650 TI - Learning curve of endoscopic pituitary surgery: Experience of a neurosurgery/ENT collaboration. AB - For neurosurgeons, who are accustomed to the binocular microscope, there is a new learning curve that must be overcome for monocular endoscopic pituitary surgery. Different studies describe a learning curve between 15 and 200 procedures, after which both operative time and complications stabilize. In this retrospective study, we evaluate the endoscopic learning curve of our group, already trained in microsurgical transsphenoidal surgery, with the assistance of ear, nose, and throat (ENT) surgeons. From 2010 to 2015, a total of 95 patients with pituitary adenomas were treated with a purely endoscopic approach. The latest 48 patients treated with the endoscope (L group) were compared with the 47 initial patients treated with the endoscope (E group) and with 43 patients treated with the microscope (M group), in terms of surgical time, complications, and tumor removal rate. The complication rate was similar in all the groups, as was the rate of total adenoma resection. Mean surgical time was shorter in the L group than in the E group (115+/-36min vs. 157+/-46 min, p<0.001); the average operative time was also shorter in the L group than in the M group (135+/-43min). The estimated reduction in duration of surgery per 10 patients was 9min (p<0.001). Over time, blood transfusions discrepantly increased from the E group to the L group (11% vs. 31%). Because of the pivotal role of ENT in the transnasal stage of 50 endoscopic procedures, we obtained an operative time comparable to that of microscopic procedures, with similar complication rate and gross total resections. Neurosurgical-ENT combined follow-up proved to be a fundamental protection from late complications. PMID- 28988651 TI - Association between polymorphism of SMAD3 gene and risk of sporadic intracranial arterial aneurysms in the Chinese Han population. AB - Intracranial arterial aneurysms (IAAs) are locally abnormal dilations of the cerebral arteries and often result in subarachnoid hemorrhages (SAH). Genetic, molecular and cellular mechanisms of sporadic IAAs forms are poorly understood. In this study, we investigate the association between mothers against decapentaplegic homolog 3 (SMAD3) genotypes and the risk of sporadic intracranial arterial aneurysms among the Chinese Han population. A case-control study was conducted examining 330 IAA patients and 313 controls. There were eight single nucleotide polymorphisms of SMAD3 selected and genotyped using the polymerase chain reaction-ligase detection reaction (PCR-LDR) method. Our results indicated that SMAD3 rs1065080 polymorphism was associated with a risk of IAAs in a codominant model (GA vs GG, OR=1.433; 95% CI 1.030-1.994; P=0.032). In summary, we observed that SMAD3 rs1065080 single nucleotide gene polymorphisms were significantly associated with patient susceptibility to IAAs. PMID- 28988652 TI - Morphologic patterns of noncontrast-enhancing tumor in glioblastoma correlate with IDH1 mutation status and patient survival. AB - Glioblastomas with a substantial proportion of noncontrast-enhancing tumour (nCET) have a variety of imaging appearances. We aimed to determine whether glioblastomas demonstrating a substantial proportion (>33%) of nCET can be sub classified by different morphologic pattern of nCET. We then assessed whether this improves the ability of MRI to predict isocitrate dehydrogenase-1 (IDH1) mutation status and whether this has prognostic significance independent of IDH1 mutation status. Pre-operative MRIs of patients with a new diagnosis of glioblastoma were reviewed. Tumours with >33% nCET were sub-classified by the dominant morphologic pattern of nCET: mass-like expansion, white matter dissemination, grey matter dissemination or a combination. IDH1 mutation status (by immunohistochemistry) and survival were compared for each pattern. 153 patients met the inclusion criteria, of whom 34 patients demonstrated >33% nCET. 10 patients had a significant mass-like component, either as the dominant pattern (n=4) or as part of a mixed pattern (n=6). The 10 patients with a significant mass-like component had longer survival than those without (median 387days, compared to 241days), though this was not statistically significant (p=0.242). Three patients had R132H-IDH1 mutations and >33% nCET, and all three had a mass like component. Using the presence of a mass-like component of nCET for predicting IDH1 mutation status improved the positive predictive value, specificity and overall accuracy of MRI. Classification of nCET by morphologic pattern improves the ability of MRI to predict IDH1 mutations and may provide useful prognostic information. PMID- 28988653 TI - Metastasectomy in older adults with urothelial carcinoma: Population-based analysis of use and outcomes. AB - BACKGROUND: Metastatic urothelial carcinoma of the bladder, ureter, or renal pelvis is a highly aggressive disease with poor outcomes. Even with platinum based chemotherapy, the median overall survival is 15 months and the 5-year survival is only 15%. The role of metastasectomy in urothelial carcinoma is currently undefined. OBJECTIVE: To examine the use and outcomes of metastasectomy in older patients with urothelial carcinoma in a large population-based dataset. DESIGN, SETTING, AND PARTICIPANTS: We conducted a SEER-Medicare study, and from 70,648 urothelial carcinoma patients who met inclusion criteria, we identified 497 patients who had at least 1 metastasectomy during a median follow-up of 40 months. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary study endpoints were metastasectomy use, the length of stay for metastasectomy, complications, and overall survival following metastasectomy. Secondary outcomes included 30-day mortality and readmission rate following metastasectomy. RESULTS AND LIMITATIONS: We identified 497 patients meeting inclusion criteria who had at least 1 metastasectomy during the study period including 24 patients who had more than 1 procedure resulting in a total of 523 metastasectomies. The median overall survival after the first metastasectomy was 19 months (95% CI: 15-23; interquartile range: 4-74). In this selected patient population, over a third of patients were alive at 3 years. In the 476 patients who had evaluable discharge dates, the median length of stay after metastasectomy was 7 days (IQR: 4-12), and 10% of patients had at least 1 complication within 30 days of discharge. Thirty day mortality after metastasectomy was 10% (n = 53/523) and was largely driven by the mortality associated with resections of urothelial cancer brain metastases. CONCLUSIONS: In well-selected patients with urothelial carcinoma with a reasonable life expectancy, resection of metastatic lesions is safe and is associated with long-term survival and potential cures. PMID- 28988654 TI - Level of knowledge among cardiac nurses regarding sexual counseling of post-MI patients in three tertiary care hospitals in Pakistan. AB - PURPOSE: The aim of this study is to measure the level of knowledge among cardiac nurses about sexual counseling of post-myocardial infarction (MI) patients. METHOD: This descriptive cross-sectional study was conducted among 153 nurses at three tertiary care hospitals of a large metropolitan city of Pakistan. RESULTS: The findings revealed that the majority nurses have moderate knowledge regarding post-MI sexual counseling. Additionally, nurses have lack of knowledge regarding effects of cardiac drugs on sexual life of post-MI patients. CONCLUSION: There is a need to improve nurses' knowledge in regard to sexual counseling among post-MI patients. Nurses should have knowledge to deal with such a sensitive issue as sexuality, in order to improve patients' quality of life. With respect to Pakistan, this was a baseline study and may provide insights for designing interventional or qualitative studies in the future. PMID- 28988655 TI - Agricultural Experiences Are Positively Associated With High School Students' Fruit and Vegetable Perceptions and Consumption. AB - OBJECTIVE: To examine the relationship between high school students' agricultural experiences and their (1) attitudes about consuming local fruits and vegetables, (2) willingness to try new fruits and vegetables, and (3) fruit and vegetable consumption. DESIGN: Cross-sectional survey research. SETTING: Public high schools in a lower-income, diverse, urban, northeastern community. PARTICIPANTS: A total of 327 students from 3 public high schools. MAIN OUTCOME MEASURE(S): Exposures were prior experience helping on a farm or community garden (yes/no) and having a home garden (yes/no). Outcomes were perceptions about local produce consumption (alpha = .73), willingness to try new fruits (alpha = .86) and vegetables (alpha = .86), and adequate fruit and vegetable consumption (yes/no) as measured by a valid 2-item cup screener. ANALYSIS: Independent t tests, 1-way ANOVA, and chi-square tests were used. RESULTS: Half of students (52.9%) reported prior farm experience; 29.7% reported having a garden at home. Few students reported consuming at least 3 cups/d of vegetables (9.8%) or 2 cups/d of fruit (37.0%). Students with prior farm experience had more favorable scores for local produce perceptions (P = .002) and willingness to try new fruits (P = .001) and vegetables (P < .001) than were students without prior experience. Students with a home garden had more favorable scores for local produce perceptions (P = .02) and willingness to try new fruits (P = .001) and vegetables (P = .001) and more often consumed adequate vegetables (P = .007) than did students without a garden. CONCLUSIONS AND IMPLICATIONS: Those working with high school students might consider offering agriculture experiences that could promote positive fruit and vegetable attitudes and behaviors. PMID- 28988656 TI - Thirty-Year Trends of Survival and Time-Varying Effects of Prognostic Factors in Patients With Metastatic Breast Cancer-A Single Institution Experience. AB - BACKGROUND: Metastatic breast cancer is generally considered an incurable disease. In our study we aimed to detect a time trend of survival over the past 30 years and account for time-varying effects of the prognostic factors. PATIENTS AND METHODS: A total of 446 patients diagnosed with breast cancer at Saint Vincent de Paul Hospital, Lille, France between 1977 and 2013 who developed metastatic disease after a disease-free interval longer than 3 months and were followed-up for outcome. Data were analyzed using the Cox proportional hazards model and presented as hazard ratios (HRs). RESULTS: A monotonic time trend of survival was detected: a 2.6% lower risk of death for each increasing year over the past 30 years. Three prognostic factors had time-varying effects; the liver first metastasis (HR during the first 16 months of follow-up: 2.26; 95% confidence interval [CI], 1.65-3.11), the bone first metastasis (HR during the first 24 months of follow-up: 0.56; 95% CI, 0.43-0.74), and the disease-free interval (HR during the first 16 months of follow-up: 0.90; 95% CI, 0.85-0.95). The brain first metastasis, multiple first metastases, the lymph node ratio, and estrogen receptor status had a constant effect over time. CONCLUSION: In our study we detected a constant time trend of improvement in prognosis of metastatic breast cancer patients over the past 30 years and identified prognostic factors with time-varying effects. PMID- 28988657 TI - Experiences of surviving a cardiac arrest after therapeutic hypothermia treatment. An interview study. AB - BACKGROUND: Cardiac arrest (CA) is often associated with high mortality. In Sweden, it is reported that 13-52 per 100,000 people suffer out-of-hospital CA, and survival to one month is 2-14%. OBJECTIVE: This study aimed to describe people's experiences of surviving a CA after therapeutic hypothermia treatment. METHOD: A descriptive qualitative design was used. Data were collected through individual interviews with seven CA survivors. The collected data were analyzed using qualitative content analysis. RESULTS: The analysis resulted in six subthemes and three emerging themes. The themes were "Dealing with issues of mortality", "Living a changed life", and "Being confident with health care and family members". CONCLUSION: Surviving a CA after therapeutic hypothermia treatment means having to deal with issues of mortality, and these patients face a turning point in life. The near-death event can create regression or progression in ethos among these patients. RELEVANCE TO CLINICAL PRACTICE: This study implies that persons who have survived a CA need support to cope. One way to provide support might be to initially establish an individualized health care plan, including bringing up existential issues and involving family members in such conversations. PMID- 28988658 TI - Impact of depression and/or anxiety on the presentation of cardiovascular events in a cohort with metabolic syndrome. StreX project: Five years of follow-up. AB - OBJECTIVES: To determine the role of anxiety and depression on the incidence of cardiovascular events (CVE) in a Catalonian population with metabolic syndrome (MetS) over a five-year follow-up according to the number/type of MetS criteria. METHODS: Prospective study to determine the incidence of CVE according to the presence of anxiety and depression disorders among individuals with different combinations of clinical traits of the MetS. SETTING: Primary Care, Catalonia (Spain). SUBJECTS: 35-75 years old fulfilling MetS criteria without CVE at the initiation of follow-up (2009). We studied 16 MetS phenotypes [NCEP-ATPIII criteria] based on the presence of depression/anxiety. The primary endpoint was the incidence of CVE at five years. RESULTS: We analyzed 401,743 people with MetS (17.2% of the population); 8.7% had depression, 16.0% anxiety and 3.8% both. 14.5% consumed antidepressants and 20.8% tranquilizers. At the 5-year follow-up, the incidence of CVE was 5.5%, being 6.4% in men and 4.4% in women. On comparing individuals with and without depression the incidence of CVE was 6.7% vs. 5.3%, respectively (p<0.01), being 5.5% in both groups in relation to anxiety. CONCLUSION: Depression and anxiety play a role in the poor prognosis of patients with MetS. In Catalonia, the two predominant MetS phenotypes do not include obesity as a criterion. PMID- 28988659 TI - Dynamics of oogenesis in ghost shrimp Callichirus major (Crustacea: Axiidea): a morphofunctional and histochemical study. AB - Callichirus major, popularly known as ghost shrimp, is a species of great importance in the fishing industry, because of its use as live bait. This study aimed to describe the different stages of the developing ovaries in C. major. Shrimps were collected along the Corujao beach, Piuma, Brazil (20 degrees 50'41.6"S 40 degrees 44'15.7"W), and the gonads were dissected for histological and histochemical analysis. The ovary consists of two elongated filaments covered by a connective tissue that divides the organ into lobules, where somatic and germ cells are found. It was possible to classify five types of germ cells: Oogonia (Oog), previtellogenic oocyte (Oc1), early vitellogenic oocyte (Oc2), late vitellogenic oocyte (Oc3) and mature oocyte (Oc4) based on their vitellogenic stage, cytoplasmic, nuclear and morphometric characteristics. The histochemical analysis demonstrated an intense reaction for proteins and polysaccharides in peripheral cytoplasm of Oc3 comparing to others cell types. According to size, volume, color intensity and distribution of oocyte types the gonads were classified into: immature, developing, developed and spent, being in females at this last stage, observed empty follicles and oocytes in reabsorption process. During oogenesis was observed a gradual increase in cytoplasmic acidophilia due to accumulation of yolk granules and the intense histochemical reaction in periphery of Oc3, which indicate the beginning of an extravitellogenic source of nutrients. Based on the microscopic analysis of the vitellogenesis, shrimp C. major showed the initial short phase of oocyte growth following with a fast vitellogenic cycle. PMID- 28988660 TI - Improving the quality of radiation oncology: 10years' experience of QUATRO audits in the IAEA Europe Region. AB - BACKGROUND AND PURPOSE: The IAEA has developed a methodology for comprehensive quality audits of radiotherapy practices called Quality Assurance Team for Radiation Oncology (QUATRO). This study explores the factors that impacted quality of care among QUATRO audited centres in the IAEA Europe Region. MATERIALS AND METHODS: The 31 QUATRO reports collected over 10years include extensive data describing the quality of radiotherapy at the audited centres. A coding key was developed to aggregate and review these data in terms of recommendations for improvement and positive findings (commendations). RESULTS: Overall 759 recommendations and 600 commendations were given. Eight centres recognized as centres of competence differed from other centres mostly because they operated complete quality management systems and were adequately staffed. Other centres had excessive staff workloads and many gaps in the process of care. Insufficient equipment levels were prevalent. Patient centredness, communication, dosimetry, quality control and radiation protection were frequently commended by QUATRO. CONCLUSIONS: This analysis points to barriers to quality care such as insufficient staffing, education/training, equipment and lack of quality management. It highlights the correlation between the human resources availability and quality of care. It has also identified common action items for enhancing quality of radiotherapy programmes in the Region. PMID- 28988661 TI - American College of Radiology-American Brachytherapy Society practice parameter for electronically generated low-energy radiation sources. AB - BACKGROUND: This collaborative practice parameter technical standard has been created between the American College of Radiology and American Brachytherapy Society to guide the usage of electronically generated low energy radiation sources (ELSs). It refers to the use of electronic X-ray sources with peak voltages up to 120 kVp to deliver therapeutic radiation therapy. MAIN FINDINGS: The parameter provides a guideline for utilizing ELS, including patient selection and consent, treatment planning, and delivery processes. The parameter reviews the published clinical data with regard to ELS results in skin, breast, and other cancers. CONCLUSIONS: This technical standard recommends appropriate qualifications of the involved personnel. The parameter reviews the technical issues relating to equipment specifications as well as patient and personnel safety. Regarding suggestions for educational programs with regard to this parameter,it is suggested that the training level for clinicians be equivalent to that for other radiation therapies. It also suggests that ELS must be done using the same standards of quality and safety as those in place for other forms of radiation therapy. PMID- 28988662 TI - Factors associated with fatigue in prostate cancer (PC) patients undergoing external beam radiation therapy (EBRT). AB - PURPOSE: Fatigue is a common adverse effect among cancer patients undergoing external beam radiation therapy (EBRT), yet the underlying disease- and treatment related factors influencing its development are poorly understood. We hypothesized that clinical, demographic, and treatment-related factors differentially affect fatigue and aimed to better characterize variables related to fatigue development in prostate cancer (PC) patients during EBRT. METHODS AND MATERIALS: We identified a cohort of 681 patients with nonmetastatic PC undergoing a 6- to 9-week EBRT course. Patient fatigue scores (range, 0-3) were prospectively recorded by providers during treatment visits using standardized criteria. Clinical and demographic factors including age, race, EBRT details, disease staging, smoking status, comorbidities, urinary symptoms, employment status, weight, and concurrent medication use were assessed for their relationship to fatigue levels. Significant differences in fatigue severity by each variable at the beginning and end of EBRT were assessed by nonparametric means testing, and differences in the level of fatigue increase over the treatment course were assessed using an ordered logistic regression model. RESULTS: Significant increases in reported fatigue severity were seen in patients with age <60 years (P = .006), depressive symptoms (P < .001), and use of androgen deprivation therapy before radiation start (P = .04). In addition, the prescription of antiemetics before radiation start was associated with reduced fatigue severity (P = .03). CONCLUSIONS: We identify factors associated with increased (young age, depressive symptoms, androgen deprivation therapy) and decreased (antiemetic prescription) fatigue in a large cohort of PC patients receiving EBRT. Continued investigation is needed to further elucidate clinical drivers and biological underpinnings of increased fatigue to guide potential interventions. PMID- 28988664 TI - Epidemiology and antimicrobial susceptibility of non-typeable Haemophilus influenzae in otitis media in Taiwanese children. AB - BACKGROUND: Concerns about non-typeable Haemophilus influenzae (NTHi) in otitis media (OM) have grown after the introduction of pneumococcal conjugate vaccine (PCV). We aim to better understand the clinical role of NTHi in pediatric OM. METHODS: Middle ear fluid samples from children <18 years with OM were obtained from 2010 to 2015. For culture-positive episodes (Streptococcus pneumoniae, H. influenzae, Moraxella catarrhalis, and Streptococcus pyogenes), patients' demographic and clinical information were reviewed and analyzed. RESULTS: A total of 783 episodes were included with 31.8% of isolates as positive. S. pneumoniae was recovered in 69.4%, NTHi in 24.6%, M. catarrhalis in 5.6%, and S. pyogenes in 4.0% of culture-positive episodes. The proportion of pneumococcal OM has declined since 2012 (P for trend <0.005), but NTHi OM rose simultaneously (P for trend = 0.009). Factors associated with increased risk of NTHi infection included less spontaneous otorrhea (OR 0.15, 95% CI 0.06-0.39, P < 0.001), absence of fever (OR 0.30, 95% CI 0.14-0.66, P = 0.003), concurrent sinusitis (OR 2.91, 95% CI 1.36 6.20, P = 0.006), previous ventilation tube insertion (OR 12.02, 95% CI 3.15 45.92, P < 0.001) and recurrent OM (OR 3.43, 95% CI 1.01-11.71, P = 0.049). The susceptibility of NTHi to amoxicillin/clavulanate was 82.0%. CONCLUSIONS: NTHi OM has trended upward in the post-PCV era. Concurrent sinusitis, previous ventilation tube insertion, and recurrent OM were associated with NTHi OM implicated a correlation between NTHi and complex OM. In consideration of NTHi infection, we suggest amoxicillin/clavulanate as the first-line therapy for OM among Taiwanese children. PMID- 28988663 TI - Risk factors for healthcare-associated infection caused by carbapenem-resistant Pseudomonas aeruginosa. AB - BACKGROUND/PURPOSE: The incidence of carbapenem-resistant Pseudomonas aeruginosa (CRPA) related healthcare-associated infection (HAI) has increased in recent year worldwide. This study is to investigate the risk factors associated with CRPA infections in a university hospital setting in Taiwan to provide more information for clinician and infection control system. METHODS: A retrospective cross sectional study was conducted from January 1st, 2009 to June 30th, 2014. Patients with P. aeruginosa related HAI were included and divided into the CRPA case group and carbapenem-susceptible Pseudomonas aeruginosa (CSPA) control group. The medical records were reviewed to identify risk factors for CRPA HAI and mortality. Patients with prior use of any anti-pseudomonal carbapenems were included in subgroup analysis. RESULTS: 395 cases of P. aeruginosa infection were enrolled from total of 3263 HAI events; 63 were CRPA and 332 were CSPA. The prevalence of CRPA was 15.9% (63/395). Significant risk factors related to CRPA infection were longer time at risk, prior use of anti-pseudomonal carbapenems, and prior use of aminoglycoside (p < 0.05, 0.01, and 0.05). Furthermore, anti pseudomonal carbapenem monotherapy did not significantly increase risk for CRPA infection. CONCLUSION: The worldwide CRPA prevalence has been on the raise and Taiwan has been also keeping up with the trend. Antimicrobials usage should be monitored carefully, especially with carbapenems and aminoglycoside. Clinicians should be award of and understand about the risk of CRPA infection, which increases by 1% with each hospitalization day. PMID- 28988665 TI - The epidemiology of non-typhoidal Salmonella gastroenteritis and Campylobacter gastroenteritis in pediatric inpatients in northern Taiwan. AB - BACKGROUND: Campylobacter and Non-typhoidal Salmonella (NTS) are the two most common bacterial pathogens associated with acute gastroenteritis in children. This study aims to elucidate the epidemiology of Campylobacter and NTS gastroenteritis and develop a scoring system to differentiate them. MATERIALS AND METHODS: This retrospective study enrolled 886 children <=18 years of age, hospitalized due to acute gastroenteritis with stool culture-proven Campylobacter or NTS infection from July 2012 to December 2015. Pearson's chi-square test and multivariate logistic regression were used to compare clinical manifestations and laboratory data. Receiver operating characteristic curves were plotted to evaluate the scoring system. RESULTS: Seasonality was found in NTS gastroenteritis from May to September, but no seasonality in Campylobacter gastroenteritis. Campylobacter jejuni and Salmonella serogroup B were the most common pathogens. The median ages were 68.2 and 18.5 months and the incidence rates of bacteremia were 0.6% and 7.1% in the Campylobacter and NTS groups, respectively. Salmonella serogroup C2 infection had the highest risk of bacteremia (OR: 5.9, 95% CI: 2.8-12.7, p < 0.001). Multivariate analysis showed significant differences in sex, age, fever, dehydration, immature WBC, CRP and Na between the two groups. A score of >=2 points indicated Campylobacter gastroenteritis, with sensitivity 75%, specificity 77%. The positive and negative predictive values were of 73.3% and 93.9% after validation. CONCLUSION: Campylobacter gastroenteritis is associated with older age and male sex, while NTS gastroenteritis is associated with moderate to severe dehydration and bacteremia. Salmonella serogroup C2 infection has the highest risk of bacteremia. PMID- 28988666 TI - Distributed synchronization of networked drive-response systems: A nonlinear fixed-time protocol. AB - The distributed synchronization of networked drive-response systems is investigated in this paper. A novel nonlinear protocol is proposed to ensure that the tracking errors converge to zeros in a fixed-time. By comparison with previous synchronization methods, the present method considers more practical conditions and the synchronization time is not dependent of arbitrary initial conditions but can be offline pre-assign according to the task assignment. Finally, the feasibility and validity of the presented protocol have been illustrated by a numerical simulation. PMID- 28988667 TI - Headless compression screw in the neuronavigation-guided and microscope-assisted treatment of spondylolysis. AB - Since 1968, many surgical techniques used in repairing the pars defect of the vertebra have been reported. Technological advances are giving rise to new ways of obtaining the best outcome using less invasive methods, which are more accurate, simple and effective. To treat cases of spondylolysis such as pseudarthrosis, we used neuro-navigation and microscopy through a 2.5-cm skin incision to approach the pars defect, freshen the fracture and place a type of screw that, until now, has never been used for this purpose. This is a novel technique, which guarantees prolonged compression and sufficient stability to facilitate the prompt healing of the vertebra. We present 2 cases of L5 spondylolysis treated with our technique, a modification of Buck's technique. A detailed description of the screw selection, surgical technical details, follow up and outcome are discussed. PMID- 28988668 TI - [Neurophysiological monitoring options in brain tumour resections. Consensus statement from the Spanish Society of Neurosurgery's (SENEC) Neuro-oncology Working Group and the Spanish Society of Clinical Neurophysiology (SENFC)]. AB - Brain tumours located in or in proximity to eloquent areas are a significant neurosurgical challenge. Performing this kind of surgery with neurophysiological monitoring to improve resections with reduced permanent focal neurological deficit has become widely accepted in the literature. However, how to conduct this monitoring, the exact definition of an eloquent area and whether to perform this surgery with the patient awake or asleep are still subject to rigorous scientific debate. Members of the Neuro-oncology Working Group (GTNO) of the Spanish Society of Neurosurgery (SENEC) and members of the Spanish Society of Clinical Neurophysiology (SENFC) have published a consensus statement to explain the different neurophysiological monitoring options currently available in awake and asleep patients to obtain better surgical resection without neurological deficits. An exhaustive review of the literature has also been conducted. PMID- 28988669 TI - [Meningeal metastasis of uterine leiomyosarcoma. Case report and literature review]. AB - Brain metastases are the most commonly seen intracranial lesions in adults. What is more, meningiomas are the most common primary intracranial tumours after gliomas and their imaging characteristics are well known in both CT and MRI scans. However, there are lesions that can mimic meningiomas in imaging studies, including metastases of extracranial tumours, confronting us with a diagnostic and therapeutic challenge. We present the case of a patient with meningeal metastasis of a uterine leiomyosarcoma that was not known at the time of the surgical intervention. PMID- 28988670 TI - Treatment Patterns and Outcomes in Early-stage Hodgkin Lymphoma in the Elderly: A National Cancer Database Analysis. AB - BACKGROUND: The outcome for early-stage (I/II) Hodgkin lymphoma (HL) has improved significantly during the past few decades. However, older age (>= 60 years) has continued to be associated with poor outcomes, and a paucity of data is available defining the optimal treatment regimens. In the present study, we sought to identify the practice patterns and outcomes in elderly patients with early-stage HL using the National Cancer Database. MATERIALS AND METHODS: We performed a retrospective study of patients aged 60 years with early-stage classic HL diagnosed from 2004 to 2012. The overall survival (OS) of patients undergoing chemotherapy (CT), radiation therapy (RT), or CT plus RT were compared. Kaplan Meier curves of OS for individual therapy were constructed and compared using the log-rank test. Multivariate analysis for predictors of mortality was conducted using the Cox proportional hazard method. RESULTS: A total of 3795 patients were included in the analysis. At baseline, 41% patients had stage I disease. Of the 3795 patients, 51% underwent CT, 16% underwent RT, and 33% underwent CT plus RT. With a median follow-up duration of 40.4 months, the unadjusted OS rates for patients receiving CT, RT, or CT plus RT were 58.1%, 54%, and 77.7%, respectively (P < .0001). On multivariate analysis, CT plus RT improved OS compared with monotherapy. CONCLUSION: In older patients (age >= 60 years) with stage I/II HL, the combination of CT plus consolidative RT resulted in improved OS compared with monotherapy. However, the use of combination therapy in this age group seems suboptimal. This could be, in part, secondary to comorbidities limiting the use of CT plus RT in the elderly. PMID- 28988671 TI - C3 deposits worsens the prognosis in type iii extracapillary glomerulonephritis. AB - INTRODUCTION: Type iii extracapillary glomerulonephritis (PEGN) is a common cause of rapidly progressive glomerulonephritis and it is usually associated with circulating anti-neutrophil cytoplasmic antibodies (ANCAs). Recent evidence points to complement activation as an important factor in the pathogenesis of PEGN. The aim of the present study was to assess the value of C3 deposits in the prognosis of PEGN. METHODS: All patients diagnosed of PEGN from 1995 to 2015 (n=72) were included in this study. Progression of renal disease in patients with positive staining for C3 by immunofluorescence was compared with those with negative staining. Mean follow up was 73 months. Progression to end-stage renal disease in relation to clinical and histological variables was analyzed. RESULTS: Positive staining for C3 was observed in 22 out of the 72 patients (30.5%). At the time of diagnosis, patients with C3 deposits had higher serum creatinine concentration than those without C3 staining (5.00 vs. 3.85mg/dl, P=0.050). Renal survival at 10 years was 36.9% in patients with positive C3 staining vs. 64.4% in patients with negative staining (P=0.005). Mortality at 10 years was higher in patients with C3 deposits than in patients without deposits (77 vs. 49.3%). CONCLUSIONS: Thus, our study shows that PEGN with deposits of C3 is associated with worse renal prognosis and greater mortality. These results would support the hypothesis that activation of the alternative pathway complement may play an important role in the generation of renal injury associated with PEGN. PMID- 28988672 TI - CEVL interactive - It is feasible for Pediatric Urology fellows to create pediatric urological surgical plans: A case study of Botox endoscopic injection. PMID- 28988673 TI - Predictive value of cortical transit time on MAG3 for surgery in antenatally detected unilateral hydronephrosis caused by ureteropelvic junction stenosis. AB - BACKGROUND: In children with antenatally detected hydronephrosis caused by ureteropelvic junction (UPJ) stenosis, the main challenge is preserving renal function by identifying children who require early surgical intervention from those for whom watchful waiting may be appropriate because of the potential for spontaneous resolution without a significant loss of renal function. OBJECTIVE: To assess the impact of initial cortical transit time (CTT) on technetium-99m mercaptoacetyltriglycerine (MAG3) diuretic renogram on the need for surgery in children with antenatally detected unilateral hydronephrosis caused by UPJ stenosis. STUDY DESIGN: We retrospectively reviewed the medical records of 33 patients with antenatally detected unilateral hydronephrosis caused by UPJ stenosis who were managed at our institution between 2006 and 2014. Delayed CTT was defined as the absence of activity in the subcortical structures within 3 min of tracer injection on a MAG3 scan. The surgical indication includes symptomatic UPJ stenosis, seriously deteriorating hydronephrosis with parenchymal thinning on serial USG, split renal function <40%, or progressive deterioration of split renal function (>5%) on a MAG3 scan. This study analyzed and compared the initial level of Society for Fetal Urology grade, anteroposterior diameter (APD), split renal function, drainage pattern on a diuretic renogram, and CTT with the need for surgery. RESULTS: Of the 33 children, 16 were classified into the delayed CTT group and 17 were placed in the normal CTT group. During the follow-up period (mean 31.8 months), surgery was needed in 75.0% (12/16) of patients in the delayed CTT group and in 5.9% (1/17) of those in the normal CTT group. Multivariate analysis showed that delayed CTT on initial MAG3 scan and APD on initial ultrasonography were independent predictive factors of the need for surgery. DISCUSSION: In this era of conservative management of antenatally detected hydronephrosis caused by UPJ stenosis, it is critical to identify which measurement on an image study is the most reliable for predicting the need for surgery by reflecting functional deterioration. In this study, multivariate analysis revealed that CTT on the initial MAG3 scan was an independent predictive factor of the need for surgery. In addition, CTT showed high negative predictive value for surgical need in children with antenatally detected unilateral hydronephrosis caused by UPJ stenosis. CONCLUSION: CTT on an initial MAG3 scan may be a useful predictor of the need for surgery in children with antenatally detected unilateral hydronephrosis caused by UPJ stenosis. PMID- 28988674 TI - Quality improvement and patient safety: Reality and responsibility from Codman to today. AB - Quality improvement and patient safety (QIPS) has become increasingly important in the practice of medicine, particularly since the Institute of Medicine's report, "To Err is Human." Despite surgery having been initially at the forefront in instituting QIPS, there has been a lag in promoting its importance until recently. A short history of QIPS is presented along with an introduction to the SQUIRE guidelines used for standardizing QIPS publications. As surgeons we are becoming even more accountable in promoting value in health care. As such, knowledge of QIPS will become an increasingly important component of our future practices and publications. PMID- 28988675 TI - Application of Geant4 Monte Carlo simulation in dose calculations for small radiosurgical fields. AB - The Geant4 toolkit was used to develop a Monte Carlo (MC)-based engine for accurate dose calculations in small radiation field sizes. The Geant4 toolkit (version 10.1.p02) was used to simulate 6-MV photon beam of a Varian2100C linear accelerator that is being used for stereotactic radiosurgery (SRS) treatment with small radiation fields. Geometric models of 3 in-house designed radiosurgical divergent cones, with the diameters of their projections at the isocenter being 10, 20, and 30 mm, were simulated. The accuracy of the MC simulation technique was examined by reproducing several different simulated dosimetric parameters of the primary beams with the experimental data. The dose distributions are first checked for single beams for each cone, then standard multiple field (SMF) techniques are applied. A sample set of DICOM files from computed tomography (CT) scan imaging of a patient's head was converted to the Geant4 geometry format to implement MC-based engine for a clinical test. To validate the accuracy of the MC based calculations for SMF arrangements, the isodose lines from MC simulation in water phantom were compared with the measured isodose lines using EBT3 Gafchromic film in Solid Water phantoms. Agreements between measured and simulated depth dose values and beam profiles for SRS cones were generally within 2%/2 mm. For output factors, the largest discrepancy was observed for 10 mm SRS cone, which was 1.7%. For SMF techniques, in SRS cones, the MC simulation and EBT3 Gafchromic film dosimetry were in acceptable agreement (5%/5 mm). Excellent agreement between the results of the MC-based and measured dose values for both single and SMF techniques in SRS cones indicates the ability of the Geant4 toolkit to be applied as the platform for treatment planning of advanced radiotherapy techniques. PMID- 28988677 TI - Incorporating different learning styles into a home exercise program. PMID- 28988676 TI - Two case reports-Use of relative motion orthoses to manage extensor tendon zones III and IV and sagittal band injuries in adjacent fingers. AB - STUDY DESIGN: Case report. INTRODUCTION: Injuries to adjacent fingers with differing extensor tendon (ET) zones and/or sagittal band pose a challenge to therapists as no treatment guidelines exist. PURPOSE OF THE STUDY: This report highlights how the relative motion flexion/extension (RMF/RME) concepts were combined into one orthosis to manage a zone IV ET repair (RME) and a zone III central slip repair (RMF) in adjacent fingers (Case 1); and how a single RME orthosis was adapted to limit proximal interphalangeal joint motion to manage multi-level ET zone III-IV injuries and a sagittal band repair in adjacent fingers (case 2). METHODS: Adapted relative motion orthoses allowed early active motion and graded exercises based on clinical reasoning and evidence. Outcomes were standard TAM% and Miller's criteria. RESULTS: 'Excellent' and 'good' outcomes were achieved by twelve weeks post surgery. Both cases returned to unrestricted work at 6 and 7 weeks. Neither reported functional deficits at discharge. DISCUSSION: Outcomes in 2 cases involving multiple digit injuries exceeded those previously reported for ET zone III-IV repairs. CONCLUSIONS: Relative motion orthoses can be adapted and applied to multi-finger injuries, eliminating the need for multiple, bulky or functionally-limiting orthoses. LEVEL OF EVIDENCE: 4. PMID- 28988678 TI - Clinical relevance commentary in response to: Repositioning the scapula with taping following distal radius fracture: Kinematic analysis using 3-dimensional motion system. PMID- 28988679 TI - Cumulative incidence of carpal instability 12-24 months after fall onto outstretched hand. AB - STUDY DESIGN: Descriptive Epidemiological Study. INTRODUCTION: Ligament tears between carpal bones are easily missed on initial presentation, but can have potentially debilitating effects on the patient if they progress to an instability. They are usually the result of a fall onto an outstretched hand with the wrist in hyperextension. Current incidence of carpal instability after these falls is unknown. PURPOSE OF THE STUDY: Using established clinical and radiological measures, we sought to establish the cumulative incidence of carpal instability in people who have fallen onto an outstretched hand in the second year after injury. We also sought to describe its relationship with functional impairment. METHODS: We used emergency department records of an inner-urban tertiary hospital to contact all patients who presented with wrist pain following fall onto outstretched hand who were between one and two years after injury. Carpal instability was defined by blinded radiological evaluations and provocative clinical tests, including Scaphoid Shift (Watson's) test, Ballottement, and mid-carpal shift test. Wrist-related pain and disability was measured using the Patient-Rated Wrist and Hand Evaluation. RESULTS: Of the 279 potentially eligible cases, only 146 were contactable, and fifty (28 male, 22 female; mean age of 48 years) attended for assessment. We found a cumulative incidence of 44% of carpal instability within the second year after injury. Of these, 12 (24%) cases had scapho-lunate instability, 12 (24%) had luno-triquetral instability and 7 (14%) had mid-carpal instability. There were no significant correlations between clinically confirmed carpal instability and pain, function, or work participation. DISCUSSION AND CONCLUSION: This study found a higher than anticipated cumulative incidence of carpal instability in the second year after injury, which may reflect volunteer bias. Patients should be advised to monitor symptoms in the year after injury and seek a review if symptoms of pain, clicking or clunking arise. LEVEL OF EVIDENCE: II. PMID- 28988680 TI - Macroscopic anisotropic bone material properties in children with severe osteogenesis imperfecta. AB - Children with severe osteogenesis imperfecta (OI) typically experience numerous fractures and progressive skeletal deformities over their lifetime. Recent studies proposed finite element models to assess fracture risk and guide clinicians in determining appropriate intervention in children with OI, but lack of appropriate material property inputs remains a challenge. This study aimed to characterize macroscopic anisotropic cortical bone material properties and investigate relationships with bone density measures in children with severe OI. Specimens were obtained from tibial or femoral shafts of nine children with severe OI and five controls. The specimens were cut into beams, characterized in bending, and imaged by synchrotron radiation X-ray micro-computed tomography. Longitudinal modulus of elasticity, yield strength, and bending strength were 32 65% lower in the OI group (p<0.001). Yield strain did not differ between groups (p>=0.197). In both groups, modulus and strength were lower in the transverse direction (p<=0.009), but anisotropy was less pronounced in the OI group. Intracortical vascular porosity was almost six times higher in the OI group (p<0.001), but no differences were observed in osteocyte lacunar porosity between the groups (p=0.086). Volumetric bone mineral density was lower in the OI group (p<0.001), but volumetric tissue mineral density was not (p=0.770). Longitudinal OI bone modulus and strength were correlated with volumetric bone mineral density (p<=0.024) but not volumetric tissue mineral density (p>=0.099). Results indicate that cortical bone in children with severe OI yields at the same strain as normal bone, and that their decreased bone material strength is associated with reduced volumetric bone mineral density. These results will enable the advancement of fracture risk assessment capability in children with severe OI. PMID- 28988682 TI - The 3Rs Concept: Time to Change How We Evaluate the Efficacy of Anthelmintics in Companion Animals. AB - Experimental infections are required by current guidelines for investigating the efficacy of anthelmintics in dogs and cats. Recently, alternatives to experimental infections and the sacrificing of research dogs and cats have been evaluated, and novel conceptual investigations and methods of examination have been explored. Several of these approaches could potentially be used in efficacy studies for anthelmintics in dogs and cats. Here, we provide food for thought towards using new tools for evaluating the efficacy of anthelmintics in companion animals, for promoting the value of field trials, and for updating the existing guidelines for the efficacy testing of anthelmintics in dogs and cats. PMID- 28988681 TI - Pathophysiology of Leishmania Infection during Pregnancy. AB - The pathological processes resulting from parasitic infection are known to have important impacts on the mother child dyad during pregnancy. The roles of parasite transmission and the maternal immune response have been described in diseases such as malaria, toxoplasmosis, and trypanosomiasis. However, the impact of parasites of the genus Leishmania, etiological agents of the neglected tropical diseases tegumentary leishmaniasis (TL) and visceral leishmaniasis (VL), is comparatively less well known, though it is an increasingly recognized concern for infected mothers and their fetuses. In this review, we first consider the pathophysiology of placental infection and transplacental transmission of this parasite, and then discuss the role and mechanisms of the maternal immune system in simultaneously mediating maternal-fetal infection and adverse pregnancy outcomes. PMID- 28988683 TI - Smoking and age-at-onset of both motor and non-motor symptoms in Parkinson's disease. AB - INTRODUCTION: Several evidence suggest that smoking may decrease the risk of Parkinson's disease and is associated with an older age-at-onset of motor signs. The relation between smoking and age-at-onset of non-motor symptoms has never been analyzed. Objective of the study is to evaluate whether smoking habit and pack-years of smoking are associated with a delay of age-at-onset of motor signs, and of some non-motor symptoms. METHODS: The study population consisted of 262 consecutive parkinsonian patients. Information on relevant demographic/clinical data focused on motor signs, REM sleep behavior disorder, constipation, depression, and hyposmia. Patients were stratified according to smoking habit (ever-versus never-smoker) and number of pack-years of smoking was computed. Repeatability of data on age-at-onset was checked 6 months after the initial interview in a randomly recruited subsample. RESULTS: Smoking habit and number of pack-years smoked were associated with an older in age-at-onset of motor signs, REM sleep behavior disorder and depression. By contrast, smoking did not affect age-at-onset of hyposmia and constipation. CONCLUSION: information from this study confirms that smoking may be associated with an older age-at-onset of motor signs, and that a similar effect can be observed on some non-motor symptoms like REM sleep behavior and depression. PMID- 28988684 TI - A nutraceutical combination of Cinnamomum cassia &Nigella sativa for Type 1 diabetes mellitus. AB - BACKGROUND: Nigella sativa (black cumin) and Cinnamomum cassia (Cinnamon) are an integral part of the Indian diet, and have also been sourced in the ayurveda, the traditional Indian system of medicine, for their medicinal properties. Both the herbs individually have been successfully evaluated for their preliminary antidiabetic potential. OBJECTIVE: Herein, we dived deeper into antidiabetic properties of these herbs, by investigating the combinatorial effect of both herbs, on parameters of diabetes and further, as an adjunct to metformin therapy, for assessing the pharmacodynamics of herb-drug interaction in diabetes mellitus. The objectives were to screen the combinatorial extract of Nigella sativa & Cinnamomum cassia's (NSCCe) alone and in combination with metformin for its potential in mitigating symptoms of diabetes mellitus-alone, and as an adjunct therapy with metformin. MATERIALS AND METHODS: Diabetes was induced in the animals by a single intraperitoneal injection of streptozotocin. Animals were divided into seven groups with 6 animals each: Vehicle control, Negative control, Positive control (Metformin 50 mg/kg), treatment groups 4 and 5 received NSCCe at the doses of 100 mg/kg and 200 mg/kg, respectively. Groups 6 and 7 received the same doses, in combination with Metformin (50 and 25 mg/kg). Following a 28-day dosing period, plasma glucose levels, lipid profile and renal function profile were evaluated. Histopathological examinations were performed to measure any morphological change in kidney, liver and pancreatic tissue. RESULTS: Combination of Nigella sativa & Cinnamomum cassia extracts significantly normalized plasma glucose levels, lipid profile and kidney function parameters, compared to the diabetic control group. Animals treated with the combinatorial extract and metformin showed more prominent effects on these parameters. Significant reversal in the pancreatic cell damage was observed on treatment with NSCCe. CONCLUSION: This study generates evidence to support Nigella sativa & Cinnamomum cassia as an adjunctive in diabetes treatment protocols. PMID- 28988685 TI - Socioeconomic disparities affect survival in malignant ovarian germ cell tumors in AYA population. AB - BACKGROUND: Malignant ovarian germ cell tumors (MOGCTs) are a rare form of ovarian malignancy. Socioeconomic status (SES) has been shown to affect survival in several gynecologic cancers. We examined whether SES impacted survival in adolescent and young adults (AYAs) with MOGCT. MATERIALS AND METHODS: The National Cancer Data Base was used to identify AYAs (aged 15-39 years) with MOGCT from 1998 to 2012. Three SES surrogate variables identified were as follows: insurance type, income quartile, and education quartile. Pooled variance t-tests and chi-square tests were used to compare tumor characteristics, the time from diagnosis to staging/treatment, and clinical outcome variables for each SES surrogate variable, while controlling for age and race/ethnicity in a multivariate model. Kaplan-Meier survival estimates were calculated using the log rank test. RESULTS: A total of 3125 AYAs with MOGCT were identified. Subjects with lower SES measures had higher overall stage and T-stage MOGCTs at presentation. There was no significant difference in the time to staging/treatment, extent of surgery, or use of chemotherapy by SES. Subjects from a lower education background, from a lower income quartile, and without insurance had decreased survival (P <= 0.02 for all). Controlling for overall stage and T-stage, the difference in survival was no longer significant. CONCLUSIONS: AYAs with MOGCT from lower SES backgrounds presented with more advanced stage disease. Further studies that focus on the underlying reasons for this difference are needed to address these disparities. PMID- 28988686 TI - Anti-angiogenic therapy in the setting of TACE: an elusive synergy? PMID- 28988687 TI - Orantinib versus placebo combined with transcatheter arterial chemoembolisation in patients with unresectable hepatocellular carcinoma (ORIENTAL): a randomised, double-blind, placebo-controlled, multicentre, phase 3 study. AB - BACKGROUND: Orantinib is an oral multi-kinase inhibitor. This study was done to evaluate the efficacy of orantinib combined with conventional transcatheter arterial chemoembolisation (cTACE) in patients with unresectable hepatocellular carcinoma. METHODS: This randomised, double-blind, placebo-controlled, phase 3 study was done at 75 sites in Japan, South Korea, and Taiwan. Patients with unresectable hepatocellular carcinoma, no extra-hepatic tumour spread, and Child Pugh score of 6 or less were randomly assigned (1:1) by interactive web response system using a computer-generated sequence to receive orantinib or placebo, within 28 days of cTACE. Randomisation was stratified by region, Child-Pugh score (5 vs 6), alpha fetoprotein concentrations (<400 ng/mL vs >=400 ng/mL), and size of the largest lesion (<=50 mm vs >50 mm). Orantinib at 200 mg, twice per day, or placebo was given orally until TACE failure or unacceptable toxicity. The patients, investigators, and study personnel were masked to treatment assignment. The primary endpoint was overall survival, analysed in the full analysis set (patients who had received at least one dose of study drug). This study is registered at ClinicalTrials.gov, number NCT01465464, and has been terminated. FINDINGS: Between Dec 10, 2010, and Nov 21, 2013, 889 patients were randomly assigned to receive either orantinib (445 patients; 444 treated) or placebo (444 patients; all treated). The study was ended at interim analysis for futility evaluation. Median follow-up was 17.3 months (IQR 11.3-26.4). There was no improvement in overall survival with orantinib compared with placebo (median 31.1 months [95% CI 26.5-34.5] vs 32.3 months [28.4-not reached]; hazard ratio 1.090, 95% CI 0.878-1.352; p=0.435). The main adverse events in the orantinib group were oedema, ascites, and elevation of aspartate and alanine aminotransferases. The most frequent adverse events of grade 3 or worse in the orantinib group included elevated aspartate aminotransferase (189 [43%] patients in the oratinib group, 161 [36%] patients in the placebo group), elevated alanine aminotransferase (150 [34%] patients in the oratinib group, 132 (30%) patients in the placebo group), and hypertension (47 [11%] patients in the oratinib group, 39 [9%] patients in the placebo group). Serious adverse events were reported in 200 (45%) patients in the orantinib group and 134 (30%) patients in the placebo group. INTERPRETATION: Orantinib combined with cTACE did not improve overall survival in patients with unresectable hepatocellular carcinoma. FUNDING: Taiho Pharmaceutical. PMID- 28988688 TI - Plasma N-terminal pro-brain natriuretic peptide concentrations before and after pericardiocentesis in dogs with cardiac tamponade secondary to spontaneous pericardial effusion. AB - OBJECTIVE: To determine if concentrations of plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) are increased in dogs with cardiac tamponade and if there is a significant increase in plasma NT-proBNP after pericardiocentesis. ANIMALS: Ten client-owned dogs with spontaneous cardiac tamponade. METHODS: Prospective clinical study. Cardiac tamponade was suspected from physical examination and confirmed with echocardiography. Blood was collected and plasma NT-proBNP concentrations were measured before and 30-60 min following pericardiocentesis and resolution of cardiac tamponade. Within-subject changes in plasma NT-proBNP were compared by the Wilcoxon signed-rank test. RESULTS: The plasma NT-proBNP concentrations measured within the reference interval in seven of 10 dogs before pericardiocentesis and in six of 10 dogs following pericardiocentesis. Following pericardiocentesis, there was a statistically significant increase in median NT-proBNP concentration (733 pmol/L, range 250 3,297) compared with the values measured before (643 pmol/L, range 250-3,210, P = 0.004). The NT-proBNP concentration increased in 90% of the dogs following pericardiocentesis. CONCLUSIONS: An upper reference limit of 900 pmol/L for plasma NT-proBNP is insensitive for the diagnosis of pericardial effusion and cardiac tamponade in dogs. Plasma NT-proBNP concentration commonly increases following pericardiocentesis, perhaps related to improved ventricular filling and stretch. PMID- 28988689 TI - Residency pathways to ambulatory care practice: Essential insights for students, residents, and educators. AB - OBJECTIVE: To provide a guiding document describing residency training opportunities in ambulatory care for students, postgraduate year 1 (PGY1) residents, practicing pharmacists, and pharmacy educators. SUMMARY: Student pharmacists, residents, practitioners, and educators can benefit from a guiding document describing the various pathways to develop as an ambulatory care practitioner through residency training. The benefits and differences of PGY1 and postgraduate year 2 (PGY2) ambulatory care residency programs are included. CONCLUSION: There are many possible training options for pharmacists interested in pursuing a career in ambulatory care pharmacy practice. In addition to the required ambulatory and community experience required for all Doctorate of Pharmacy students, postgraduate training in an ambulatory environment can allow for specialization. Candidates for residency training can complete a PGY1 pharmacy residency or a PGY1 community-based pharmacy residency, possibly followed by a PGY2 ambulatory care residency. Career paths for ambulatory care pharmacists vary regionally across the country according to competition for positions, local availability of training programs, and the experience of regional leaders. A comprehensive description of these available training pathways and advantages of each are beneficial for students, residents, practicing pharmacists, and educators. PMID- 28988691 TI - Energetics: An emerging frontier in cellular mechanosensing: Reply to comments on "Cellular mechanosensing of the biophysical microenvironment: A review of mathematical models of biophysical regulation of cell responses". AB - How do cells can sense the substrate stiffness? Our recent review highlighted a range of theoretical models and simulations that have been proposed to answer this important question. In response to this review, three leading groups in the field noted some important omissions not only from our review itself but also from the field. These groups noted, correctly, that much of our understanding of cellular mechanosensing arises from models that take advantage of equilibrium thermodynamics, and that this is inappropriate because living cells are never in thermodynamic equilibrium. In this response, we highlight some promising research aimed at resolving this conundrum. PMID- 28988692 TI - The survey on cellular and tissue-engineered therapies in Europe and neighboring Eurasian countries in 2014 and 2015. AB - BACKGROUND AIMS: With the support of five established scientific organizations, this report, the seventh of its kind, describes activity in Europe for the years 2014 and 2015 in the area of cellular and tissue-engineered therapies, excluding hematopoietic stem cell (HSC) treatments for the reconstitution of hematopoiesis. METHODS: In 2015 [respectively 2014], 205 [276] teams from 32 countries responded to the cellular and tissue-engineered therapy survey; 178 [126] teams reported treating 3686 [2665] patients. RESULTS: Indications were musculoskeletal/rheumatological disorders (32% [33%]), cardiovascular disorders (12% [21%]), hematology/oncology (predominantly prevention or treatment of graft versus host disease and HSC graft enhancement; 20% [20%]), neurological disorders (4% [6%]), gastrointestinal disorders (<1% [1%]) and other indications (31% [20%]). The majority of autologous cells (60% [73%]) were used to treat musculoskeletal/rheumatological (44% [36%]) disorders, whereas allogeneic cells were used mainly for hematology/oncology (61% [68%]). The reported cell types were mesenchymal stromal cells (40% [49%]), chondrocytes (13% [6%]), hematopoietic stem cells (12% [23%]), dermal fibroblasts (8% [3%]), dendritic cells (2% [2%]), keratinocytes (1% [2%]) and others (24% [15%]). Cells were expanded in vitro in 63% [40%] of the treatments, sorted in 16% [6%] of the cases and rarely transduced (<1%). Cells were delivered predominantly as suspension 43% [51%], intravenously or intra-arterially (30% [30%]), or using a membrane/scaffold (25% [19%]). DISCUSSION: The data are compared with those from previous years to identify trends in a still unpredictably evolving field. Perspectives of representatives from plastic surgery practitioners, Iran and ISCT are presented (contributing authors D.A. Barbara, B. Hossein and W.L. Mark, respectively). PMID- 28988690 TI - Impact of number of co-existing rotors and inter-electrode distance on accuracy of rotor localization. AB - BACKGROUND: Conflicting evidence exists on the efficacy of focal impulse and rotor modulation on atrial fibrillation ablation. A potential explanation is inaccurate rotor localization from multiple rotors coexistence and a relatively large (9-11mm) inter-electrode distance (IED) of the multi-electrode basket catheter. METHODS AND RESULTS: We studied a numerical model of cardiac action potential to reproduce one through seven rotors in a two-dimensional lattice. We estimated rotor location using phase singularity, Shannon entropy and dominant frequency. We then spatially downsampled the time series to create IEDs of 2 30mm. The error of rotor localization was measured with reference to the dynamics of phase singularity at the original spatial resolution (IED=1mm). IED has a significant impact on the error using all the methods. When only one rotor is present, the error increases exponentially as a function of IED. At the clinical IED of 10mm, the error is 3.8mm (phase singularity), 3.7mm (dominant frequency), and 11.8mm (Shannon entropy). When there are more than one rotors, the error of rotor localization increases 10-fold. The error based on the phase singularity method at the clinical IED of 10mm ranges from 30.0mm (two rotors) to 96.1mm (five rotors). CONCLUSIONS: The magnitude of error of rotor localization using a clinically available basket catheter, in the presence of multiple rotors might be high enough to impact the accuracy of targeting during AF ablation. Improvement of catheter design and development of high-density mapping catheters may improve clinical outcomes of FIRM-guided AF ablation. PMID- 28988693 TI - Circulating CD8+CD28- suppressor T cells tied to poorer prognosis among metastatic breast cancer patients receiving adoptive T-cell therapy: A cohort study. AB - BACKGROUND AIMS: This study aimed to determine the prognostic value of circulating CD8+CD28- T lymphocytes among breast cancer patients treated with adoptive T-lymphocyte immunotherapy after chemotherapy. METHODS: Two hundred and thirty-two breast cancer patients underwent adoptive T-cell immunotherapy. Circulating CD8+CD28- proportion was measured by flow cytometry. Median proportion of CD8+CD28- was 24.2% and set as the categorical cutoff value for further analysis. The median survival was estimated by Kaplan-Meier curve, with difference detection and hazard ratio estimation by log-rank test and Cox hazard proportion regression model. RESULTS: With adoptive T-cell therapy, patients with higher CD8+CD28- levels experienced median progression-free and overall survival of 7.1 months and 26.9 months, respectively-significantly shorter than patients with lower levels (11.8 and 36.2 months). CD8+CD28- proportion >24.2% demonstrated a hazard ratio (HR) of 2.06 (95% confidence interval [CI] 1.31-3.12) for progression and an HR of 1.97 (95% CI 1.06-3.67) for death. Among patients who had received previous first-line chemotherapy, CD8+CD28- proportion >24.2% demonstrated an HR of 2.66 (95% CI 1.45-4.88) for progression. Among patients exposed to previous second-line or higher chemotherapy, CD8+CD28- proportion >24.2% demonstrated a 486% higher risk for death (HR = 5.86, 95% CI 1.77-19.39). A 1% increase in suppressive T cells was associated with a 5% increased risk of death. DISCUSSION: Elevated peripheral blood CD8+CD28- was associated with poorer prognosis for metastatic breast cancer, especially for higher risk of progression among patients with first-line chemotherapy and higher risk of death among patients with more than second-line chemotherapy. PMID- 28988694 TI - Do Textiles Impact DXA Bone Density or Body Composition Results? AB - External artifacts can confound dual-energy X-ray absorptiometry (DXA) measurements. It is often accepted that garments free of metal do not affect DXA results; however, little data exist in this regard. It is plausible that some textiles absorb radiation and thereby alter DXA results. We hypothesized that some dense or synthetic textiles, for example, reflective materials, might alter DXA-measured bone and soft tissue mass. Hologic and GE Lunar spine phantoms and a Bioclinica prototype total body phantom were imaged on a GE Lunar iDXA and Prodigy densitometer. Each phantom was scanned 10 times to establish mean values. Subsequently, 2 layers of various fabrics were placed over the entire top surface of the phantom, and 10 scans were performed without repositioning. Samples of natural, synthetic, or embellished fabric (including those with reflective material) and of varying thickness were used. Wilcoxon signed rank tests were used to compare the means between bare phantom and textile-covered phantom. Significant differences were demonstrated often, depending on the scanner, phantom, and textile used. A polyester fabric with reflective strip consistently altered measurements. For example, this fabric increased measured mean lumbar spine bone mineral density and total body bone mineral content by 0.008 g/cm2 and 3.6 g, respectively (p < 0.01). Similarly, mean total body fat decreased (-173 g) and lean mass increased (+213 g; p < 0.01). Fat and lean mass were also affected by metallic thread, wool, blend denim, and shiny polyester (p < 0.05), and lean mass was affected by cotton denim and sweatshirt material (p < 0.0003). In conclusion, textiles can affect DXA-measured bone mineral density and body composition results. Even small amounts of reflective material could alter mass measurements by ~25% of the least significant change. Clothing made of dense textiles (e.g., wool and denim) or those with reflective material and metallic thread should be avoided during DXA scanning. PMID- 28988695 TI - Temporal Trends in Clinical and Pathological Characteristics for Men Undergoing Radical Prostatectomy Between 1995 and 2013 at Rigshospitalet, Copenhagen, Denmark, and Stanford University Hospital, United States. AB - PURPOSE: To analyze how prostate-specific antigen (PSA) screening and practice patterns has affected trends in tumor characteristics in men undergoing radical prostatectomy (RP) in the United States and Denmark. Unlike in the United States, PSA screening has not been recommended in Denmark. PATIENTS AND METHODS: We performed an observational register study using pre- and postoperative data on 2168 Danish patients from Rigshospitalet, Copenhagen, Denmark, and 2236 patients from Stanford University Hospital, Stanford, CA, who underwent RP between 1995 and 2013. Patients were stratified according to Cancer of the Prostate Risk Assessment-Postsurgical (CAPRA-S) risk groups and D'Amico risk classification and were clustered into 4 time periods (1995-1999, 2000-2004, 2005-2009, and 2010 2013). Temporal trends in the proportions of patients of a given variable at the 2 institutions were evaluated with Cochran-Armitage test for trends and chi square testing. RESULTS: A total of 4404 patients were included. Temporal changes in preoperative PSA, age, grade, and stage was found in both cohorts. Median preoperative PSA declined in both cohorts, while median age increased, with the Danish cohort showing the greatest changes in both PSA and age. In both cohorts, there was a trend for higher-risk preoperative features before RP over time. In 2010-2013, 27.7% and 21.8% of the patients were in the D'Amico high-risk group at Copenhagen and Stanford, respectively. CONCLUSION: Despite recommendation against PSA screening in Denmark, Danish men undergoing RP at Rigshospitalet to a considerable extent now resemble American men undergoing RP at Stanford. At both sites, there is continued trend to reduce the number of men undergoing RP for low risk prostate cancer. PMID- 28988696 TI - Phospholipases during membrane dynamics in malaria parasites. AB - Plasmodium parasites, the causative agents of malaria, display a well-regulated lipid metabolism required to ensure their survival in the human host as well as in the mosquito vector. The fine-tuning of lipid metabolic pathways is particularly important for the parasites during the rapid erythrocytic infection cycles, and thus enzymes involved in lipid metabolic processes represent prime targets for malaria chemotherapeutics. While plasmodial enzymes involved in lipid synthesis and acquisition have been studied in the past, to date not much is known about the roles of phospholipases for proliferation and transmission of the malaria parasite. These phospholipid-hydrolyzing esterases are crucial for membrane dynamics during host cell infection and egress by the parasite as well as for replication and cell signaling, and thus they are considered important virulence factors. In this review, we provide a comprehensive bioinformatic analysis of plasmodial phospholipases identified to date. We further summarize previous findings on the lipid metabolism of Plasmodium, highlight the roles of phospholipases during parasite life-cycle progression, and discuss the plasmodial phospholipases as potential targets for malaria therapy. PMID- 28988697 TI - Diagnosis and management of patients with significantly abnormal glycaemic profiles during pregnancy after bariatric surgery: PRESAGE (Pregnancy with significantly abnormal glycaemic exposure - bariatric patients). PMID- 28988698 TI - Dissemination of successful international clone ST15 and clonal complex 17 among Bulgarian CTX-M-15 producing K. pneumoniae isolates. AB - A total of 82 extended spectrum beta-lactamase (ESBL) producing Klebsiella pneumoniae and 4 Klebsiella oxytoca isolates were collected in 2014 from four geographical areas in Bulgaria and their multilocus sequence type (MLST) and transferability of the ESBL encoding genes were investigated. The predominant type was CTX-M-15 (87%), followed by CTX-M-3 (9%), SHV-12 or SHV-2 (2%) and CTX-M 14 (1%). The CTX-M-15 producers belonged to ST15 (34.1%) and to a lesser extent to CC17 (ST16, ST17, ST336). The CTX-M-15 transconjugants showed a presence of R, A/C2 and F replicons. The CTX-M-3 producers were assigned to ST29, ST70, ST432, ST542 and ST15 types and the transconjugants carried M2 replicons. To the best of our knowledge, this is the first report that fully describes the MLST types among Bulgarian ESBL producing K. pneumoniae and the first report of the detection of IncR plasmid replicon type in our country. PMID- 28988699 TI - Disruption of Ankyrin B and Caveolin-1 Interaction Sites Alters Na+,K+-ATPase Membrane Diffusion. AB - The Na+,K+-ATPase is a plasma membrane ion transporter of high physiological importance for ion homeostasis and cellular excitability in electrically active tissues. Mutations in the genes coding for Na+,K+-ATPase alpha-subunit isoforms lead to severe human pathologies including Familial Hemiplegic Migraine type 2, Alternating Hemiplegia of Childhood, Rapid-onset Dystonia Parkinsonism, or epilepsy. Many of the reported mutations lead to change- or loss-of-function effects, whereas others do not alter the functional properties, but lead to, e.g., reduced protein stability, reduced protein expression, or defective plasma membrane targeting. Na+,K+-ATPase frequently assembles with other membrane transporters or cellular matrix proteins in specialized plasma membrane microdomains, but the effects of these interactions on targeting or protein mobility are elusive so far. Mutation of established interaction motifs of the Na+,K+-ATPase with ankyrin B and caveolin-1 are expected to result in changes in plasma membrane targeting, changes of the localization pattern, and of the diffusion behavior of the enzyme. We studied the consequences of mutations in these binding sites by monitoring diffusion of eGFP-labeled Na+,K+-ATPase constructs in the plasma membrane of HEK293T cells by fluorescence correlation spectroscopy as well as fluorescence recovery after photobleaching or photoswitching, and observed significant differences compared to the wild-type enzyme, with synergistic effects for combinations of interaction site mutations. These measurements expand the possibilities to study the consequences of Na+,K+ ATPase mutations and provide information about the interaction of Na+,K+-ATPase alpha-isoforms with cellular matrix proteins, the cytoskeleton, or other membrane protein complexes. PMID- 28988700 TI - Differences in Adverse Event Reporting Rates of Therapeutic Failure Between Two Once-daily Extended-release Methylphenidate Medications in Canada: Analysis of Spontaneous Adverse Event Reporting Databases. AB - PURPOSE: Our study evaluated adverse events of therapeutic failure (and specifically reduced duration of action) with the use of a branded product, Osmotic Release Oral System (OROS) methylphenidate, which is approved for the treatment of attention deficit/hyperactivity disorder, and a generic product (methylphenidate, methylphenidate ER-C), which was approved for marketing in Canada based on bioequivalence to OROS methylphenidate. This study was initiated following reports that some US-marketed generic methylphenidate ER products had substantially higher reporting rates of therapeutic failure than did the referenced brands. METHODS: Through methodology similar to that used by the US Food and Drug Administration to investigate the issue with the US-marketed generic, reporting rates were calculated from cases of therapeutic failure identified in the Canadian Vigilance Adverse Reaction Online database for a 1 year period beginning 8 months after each product launch. Corresponding population exposure was estimated from the number of tablets dispensed. An in depth analysis of narratives of individual case safety reports (ICSRs) with the use of the generic product was conducted in duplicate by 2 physicians to assess causality and to characterize the potential safety risk and clinical pattern of therapeutic failure. Similar secondary analyses were conducted on the US-marketed products. FINDINGS: Reporting rates of therapeutic failure with the use of methylphenidate ER-C (generic) and OROS methylphenidate (brand name) were 411.5 and 37.5 cases per 100,000 patient-years, respectively (reporting rate ratio, 10.99; 95% CI, 5.93-22.21). In-depth analysis of narratives of 230 ICSRs of therapeutic failure with the Canadian-marketed generic determined that all ICSRs were either probably (60 [26%]) or possibly (170 [74%]) causally related to methylphenidate ER-C. Clinical symptoms suggestive of overdose were present in 31 reports of loss of efficacy (13.5%) and occurred primarily in the morning, and premature loss of efficacy (shorter duration of action) was described in 98 cases (42.6%) and occurred primarily in the afternoon. Impacts on social functioning, such as disruption in work or school performance or adverse social behaviors, were found in 51 cases (22.2%). IMPLICATIONS: The ~10-fold higher reporting rate of therapeutic failure with the generic product relative to its reference product in the present Canadian study resembles findings with US-marketed generic products. While these results should be interpreted with caution due to the limitations of spontaneous adverse event reporting, which may confound comparisons across products, similar findings nonetheless led the US Food and Drug Administration to declare in 2014 that 2 methylphenidate ER generic products in the United States were neither bioequivalent nor interchangeable with OROS methylphenidate-their reference product. Our results indicate a potential safety issue with the Canadian-marketed generic and suggest a need for further investigation by Health Canada. PMID- 28988701 TI - Choosing the Active X: The Human Version of X Inactivation. AB - Humans and rodents differ in how they carry out X inactivation (XI), the mammalian method to compensate for the different number of X chromosomes in males and females. Evolutionary changes in staging embryogenesis and in mutations within the XI center alter the process among mammals. The mouse model of XI is predicated on X counting and subsequently choosing the X to 'inactivate'. However, new evidence suggests that humans initiate XI by protecting one X in both sexes from inactivation by XIST, the noncoding RNA that silences the inactive X. This opinion article explores the question of how the active X is protected from silencing by its own Xist locus, and the possibility of different solutions for mouse and human. PMID- 28988702 TI - Prognosis of sporadic resected small (<=2 cm) nonfunctional pancreatic neuroendocrine tumors - a multi-institutional study. AB - BACKGROUND: Malignant potential of small (<=20 mm) nonfunctional pancreatic neuroendocrine tumors (sNF-PNET) is difficult to predict and management remain controversial. The aim of this study was to assess the prognosis of sporadic nonmetastatic sNF-PNETs. METHODS: Patients were identified from databases of 16 centers. Outcomes and risk factors for recurrence were identified by uni- and multivariate analyses. RESULTS: sNF-PNET was resected in 210 patients, and 66% (n = 138) were asymptomatic. Median age was 60 years, median tumor size was 15 mm, parenchyma-sparing surgery was performed in 42%. Postoperative mortality was 0.5% (n = 1), severe morbidity rate was 14.3% (n = 30), and 14 of 132 patients (10.6%) with harvested lymph nodes had metastatic lymph nodes. Tumor size, presence of biliary or pancreatic duct dilatation, and WHO grade 2-3 were independently associated with recurrence. Patients with tumors sized <=10 mm were disease free at last follow-up. The 1-, 3- and 5-year disease-free survival rates for patients with tumors sized 11-20 mm on preoperative imaging were 95.1%, 91.0%, and 87.3%, respectively. CONCLUSIONS: In sNF-PNETs, the presence of biliary or pancreatic duct dilatation or WHO grade 2-3 advocate for surgical treatment. In the remaining patients, a wait-and-see policy might be considered. PMID- 28988703 TI - Cost of achieving equivalent outcomes in sicker patients after liver transplant. AB - BACKGROUND: We aimed to characterize variability in cost after straightforward orthotopic liver transplant (OLT). METHODS: Using the University HealthSystem Consortium and Scientific Registry of Transplant Recipients databases, we identified patients who underwent OLT between 2011 and 2014. Patients meeting criteria for straightforward OLT, defined as length of stay < 14 days with discharge to home, were selected (n = 5763) and grouped into tertiles (low, medium, high) according to cost of perioperative stay. RESULTS: Patients undergoing straightforward OLT were of similar demographics regardless of cost. High cost patients were more likely to require preoperative hemodialysis, had higher severity of illness, and higher model for end-stage liver disease (MELD) (p < 0.01). High cost patients required greater utilization of resources including lab tests, blood transfusions, and opioids (p < 0.01). Despite having higher burden of disease and requiring increased resource utilization, high cost OLT patients with a straightforward perioperative course were shown to have identical 2-year graft and overall survival compared to lower cost patients (p = 0.82 and p = 0.63), respectively. CONCLUSION: Providing adequate perioperative care for OLT patients with higher severity of illness and disease burden requires increased cost and resource utilization; however, doing so provides these patients with long term survival equivalent to more routine patients. PMID- 28988704 TI - Fungal Infections of the Central Nervous System in Small Animals: Clinical Features, Diagnosis, and Management. AB - Small animal mycoses vary geographically. Different clinical presentations are seen in animals with infection of the central nervous system (CNS), including multifocal meningoencephalomyelitis, intracranial lesions that accompany sinonasal lesions, rapidly progressive ventriculitis, or solitary granuloma of the brain or spinal cord. Systemic, nasal, or extraneural clinical signs are common but, especially in granuloma cases, do not always occur. Surgery may have a diagnostic and therapeutic role in CNS granuloma. There have been recent advancements in serology. Fluconazole, voriconazole, and posaconazole cross the blood-brain barrier, but voriconazole is neurotoxic to cats. Liposomal and lipid encapsulated formulations of amphotericin B are preferred. PMID- 28988705 TI - Implementing Head and Neck Contouring Peer Review without Pathway Delay: The On demand Approach. AB - AIMS: Peer review of contour volume is a priority in the radiotherapy treatment quality assurance process for head and neck cancer. It is essential that incorporation of peer review activity does not introduce additional delays. An on demand peer review process was piloted to assess the feasibility and efficiency of this approach, as compared with a historic scheduled weekly approach. MATERIALS AND METHODS: Between November 2016 and April 2017 four head and neck clinicians in one centre took part in an on-demand peer review process. Cases were of radical or adjuvant intent of any histology and submitted on a voluntary basis. The outcome of contour peer review would be one of unchanged (UC), unchanged with variation or discretion noted (UV), minor change (M) or significant change (S). The time difference between the completion of the on demand peer review was compared with the time difference to a hypothetical next Monday or Tuesday weekly peer review meeting. The time taken to review each case was also documented in the latter period of the pilot project. RESULTS: In total, 62 cases underwent peer review. Peer review on-demand provided dosimetrists with an average of an extra two working days available per case to meet treatment start dates. The proportion of cases with outcomes UC, UV, M and S were 45%, 16%, 26% and 13%, respectively. The mean peer review time spent per case was 17 min (12 cases). The main reason for S was discrepancy in imaging interpretation (4/8 cases). A lower proportion of oropharyngeal cases were submitted and had S outcomes. A higher proportion of complex cases, e.g. sinonasal/nasopharynx location or previous downstaging chemotherapy had S outcomes. The distribution of S outcomes appears to be similar regardless of clinician experience. The level of peer review activity among individuals differed by workload and job timetable. CONCLUSION: On-demand peer review of the head and neck contour volume is feasible, reduces delay to the start of dosimetry planning and bypasses the logistical barriers of weekly meetings. An audit of participation will be required to ensure successful implementation. PMID- 28988707 TI - Pseudoaneurysm of the ascending thoracic aorta years after aortic valve replacement. AB - Aortic pseudoaneurysm (PSA) formation post aortic valve replacement is one of the rare and devastating complications if left untreated. Aortic PSA can occur few weeks or month after surgery. The spectrum of symptoms varies from dyspnea, wide pulse pressure, and chest pain. However, in rare cases, aortic root PSA could be asymptomatic. Aortic PSA mortality could be as high as 70%, if left untreated. Therefore, High clinical suspicion and prompt surgical intervention is imperative. In this case, the patient presented with dyspnea years after Bentall procedure, and imaging studies revealed para-aortic PSA that was treated surgically. PMID- 28988706 TI - Potential role of IL-37 in atherosclerosis. AB - IL-37 is a member of the IL-1 family, but unlike most other members of this family of cytokines, it has wide-ranging anti-inflammatory properties. Initially shown to bind IL-18 binding protein and prevent IL-18-mediated inflammation, its known role has been expanded to include distinct pathways, both intracellular involving the transcription factor Smad3, and extracellular via binding to the orphan receptor IL-1R8. A number of recent publications investigating the role of IL-37 in atherosclerosis and ischemic heart disease have revealed promising therapeutic value of the cytokine. Although research concerning the role of IL-37 and its mechanism in atherosclerosis is relatively scant, there are a number of well-known atherosclerotic processes that this cytokine can mediate with the potential of modulating the disease progression itself. This review will probe in detail the effects of IL-37 on important pathological processes such as inflammation, dysregulated lipid metabolism, and apoptosis, by analyzing existing data as well as exploring the potential of this cytokine to influence these properties. PMID- 28988708 TI - Efficacy of a heparin based rota-flush solution in patients undergoing rotational atherectomy. AB - INTRODUCTION: The efficacy of heparin based flush solutions in rotational atherectomy (RA) has not been validated. Recently, a single center study demonstrated the feasibility of an alternative flush solution with 10,000U of unfractionated heparin (UFH) in 1L of normal saline. We aimed to evaluate the safety and efficacy of an alternative flush solution intermittently utilized at our institution. METHODS: We retrospectively identified 150 patients undergoing RA over a three year period. One hundred cases utilized an alternative flush solution containing 10,000U UFH, 400mcg nitroglycerin, and 10mg verapamil in 1L normal saline and fifty cases utilized RotaGlide Lubricant (Boston Scientific) in addition to heparin and vasodilators in the same dose. The primary end point was to compare rates of procedural success. Secondary endpoints were to report procedural characteristics including the incidence of major adverse cardiac events (MACE) and minor periprocedural complications. RESULTS: Procedural success was achieved in 98% (98/100) of cases utilizing the alternative Rota-Flush solution compared to 100% (50/50) in the Rota-Glide group (P=0.553). A total of 292 lesions (200 Rota-Flush vs 92 Rota-Glide) were targeted for intervention. MACE occurred in 13 (13%) and 4 (8%) cases in the Rota-Flush and Rota-Glide groups, respectively (P=0.425). CONCLUSION: Rotational atherectomy performed with the previously defined Rota-Flush or Rota-Glide solutions resulted in similar rates of procedural success. There were no significant disparities in incidence of MACE and minor periprocedural complications between the two groups. Heparin based rota-flush solutions can be effective alternatives to traditional solutions containing RotaGlide Lubricant. PMID- 28988709 TI - Identification and characterization of a potent and selective inhibitor of human urate transporter 1. AB - BACKGROUND: Selective inhibitors of human urate transporter 1 (hURAT1) are considered to be effective treatment for hyperuricemia and gout, which can reduce the reabsorption of more than 90% of uric acid in the proximal tubule of the kidney. We aimed to design and synthesize a more potent hURAT1 based on the structure of Lesinurad (LU), which was reported to lower uric acid levels with IC50 value of hURAT1 (about 60MUM). METHODS: A cell model was conducted and characterized via Real-time qRCR and Western blot. We synthesized and identified a new midazole analogue of LU. Cells stably-expressing hURAT1 or human organic anion transporter 1 (hOAT1) were used in the [14C] urate or 6-carboxyfluorescein (6-CF) uptake assays to test the activities of the newly synthesized compound. The uric acid lowering effects of LU and LUM and their effects on urea nitrogen and creatinine in potassium oxonate-induced hyperuricemic rats were analyzed. RESULTS: The [14C] Urate uptake assay using hURAT1 stably transfected MDCK cells indicated that LUM was more potent than LU against hURAT1, with IC50 values of 3.22MUM and 65.47MUM, respectively. LU and LUM also effectively suppressed hOAT1 mediated 6-CF uptake, and the IC50 hURAT1/IC50 hOAT1 of LU and LUM was1.49 and 0.35 respectively, indicating a better selectivity for LUM than LU. In vivo, LUM Na (40mg/kg) showed more potent activity in reducing serum uric acid levels in potassium oxonate-induced hyperuricemic rats, compared to similar doses of LU-Na. CONCLUSION: LUM was demonstrated to be as potent a uricosuric drug as LU. PMID- 28988710 TI - Do Interventions Intended to Increase Female Medical Student Interest in Radiology Work? Preliminary Findings. AB - PURPOSE: The purpose of this study is to share the preliminary findings after initiation of interventions at the medical school level, which have been suggested by the literature to increase female medical student interest in radiology at one institution. Additionally, the paper provides discussion of how to better future interventions for increasing female medical student interest. METHODS: Interventions to increase medical student exposure to radiology were implemented at the University of Massachusetts Medical School in 2012. Radiology was incorporated into the preclinical curriculum; flexible clinical experiences stressing patient contact were created for early exposure to radiology during third-year clerkships; and a 'Women in Radiology' panel was held to promote visibility of female radiologists. In addition, female radiology faculty became more involved in medical school activities and events. RESULTS: Our results suggest that early exposure in the preclinical curriculum and patient-centered electives increase overall student interest in radiology but only minimally increase female interest. Simply offering the patient-centered electives is not enough as it resulted in more male student enrollment than female (60% vs. 40%, respectively). Just one event promoting visibility of female radiologists changed female medical student perception of patient contact within radiology by a statistically significant amount. Examination of current UMass faculty radiologists by gender demonstrates that full-time, junior female radiologists the demographic suggested to have the biggest impact on female medical students only accounted for 4% of faculty. CONCLUSION: This article may be informative for radiology departments looking to increase female medical student interest. Required visibility of female radiologists and active publicity of female radiologists from the first preclinical year are likely to have the biggest impact in increasing female medical student interest. PMID- 28988711 TI - In Vivo Selection of a Computationally Designed SCHEMA AAV Library Yields a Novel Variant for Infection of Adult Neural Stem Cells in the SVZ. AB - Directed evolution continues to expand the capabilities of complex biomolecules for a range of applications, such as adeno-associated virus vectors for gene therapy; however, advances in library design and selection strategies are key to develop variants that overcome barriers to clinical translation. To address this need, we applied structure-guided SCHEMA recombination of the multimeric adeno associated virus (AAV) capsid to generate a highly diversified chimeric library with minimal structural disruption. A stringent in vivo Cre-dependent selection strategy was implemented to identify variants that transduce adult neural stem cells (NSCs) in the subventricular zone. A novel variant, SCH9, infected 60% of NSCs and mediated 24-fold higher GFP expression and a 12-fold greater transduction volume than AAV9. SCH9 utilizes both galactose and heparan sulfate as cell surface receptors and exhibits increased resistance to neutralizing antibodies. These results establish the SCHEMA library as a valuable tool for directed evolution and SCH9 as an effective gene delivery vector to investigate subventricular NSCs. PMID- 28988712 TI - Antimicrobial Peptide Combined with BMP2-Modified Mesenchymal Stem Cells Promotes Calvarial Repair in an Osteolytic Model. AB - Repair and regeneration of inflammation-induced bone loss remains a clinical challenge. LL37, an antimicrobial peptide, plays critical roles in cell migration, cytokine production, apoptosis, and angiogenesis. Migration of stem cells to the affected site and promotion of vascularization are essential for tissue engineering therapy, including bone regeneration. However, it is largely unknown whether LL37 affects mesenchymal stem cell (MSC) behavior and bone morphogenetic protein 2 (BMP2)-mediated bone repair during the bone pathologic remodeling process. By performing in vitro and in vivo studies with MSCs and a lipopolysaccharide (LPS)-induced mouse calvarial osteolytic bone defect model, we found that LL37 significantly promotes cell differentiation, migration, and proliferation in both unmodified MSCs and BMP2 gene-modified MSCs. Additionally, LL37 inhibited LPS-induced osteoclast formation and bacterial activity in vitro. Furthermore, the combination of LL37 and BMP2 markedly promoted MSC-mediated angiogenesis and bone repair and regeneration in LPS-induced osteolytic defects in mouse calvaria. These findings demonstrate for the first time that LL37 can be a potential candidate drug for promoting osteogenesis and for inhibiting bacterial growth and osteoclastogenesis, and that the combination of BMP2 and LL37 is ideal for MSC-mediated bone regeneration, especially for inflammation induced bone loss. PMID- 28988713 TI - Otx2-Genetically Modified Retinal Pigment Epithelial Cells Rescue Photoreceptors after Transplantation. AB - Inherited retinal degenerations are blinding diseases characterized by the loss of photoreceptors. Their extreme genetic heterogeneity complicates treatment by gene therapy. This has motivated broader strategies for transplantation of healthy retinal pigmented epithelium to protect photoreceptors independently of the gene causing the disease. The limited clinical benefit for visual function reported up to now is mainly due to dedifferentiation of the transplanted cells that undergo an epithelial-mesenchymal transition. We have studied this mechanism in vitro and revealed the role of the homeogene OTX2 in preventing dedifferentiation through the regulation of target genes. We have overexpressed OTX2 in retinal pigmented epithelial cells before their transplantation in the eye of a model of retinitis pigmentosa carrying a mutation in Mertk, a gene specifically expressed by retinal pigmented epithelial cells. OTX2 increases significantly the protection of photoreceptors as seen by histological and functional analyses. We observed that the beneficial effect of OTX2 is non-cell autonomous, and it is at least partly mediated by unidentified trophic factors. Transplantation of OTX2-genetically modified cells may be medically effective for other retinal diseases involving the retinal pigmented epithelium as age-related macular degeneration. PMID- 28988714 TI - Genome-wide Mapping of Off-Target Events in Single-Stranded Oligodeoxynucleotide Mediated Gene Repair Experiments. AB - Short single-stranded oligodeoxynucleotides are versatile molecular tools used in different applications. They enable gene repair and genome editing, and they are central to the antisense technology. Because the usability of single-stranded oligodeoxynucleotides depends on their efficiencies, as well as their specificities, analyzing their genotoxic off-target activities is important. Thus, we have developed a protocol that follows the fate of a biotin-labeled single-stranded oligodeoxynucleotide in human cells based on its physical incorporation into the targeted genome. Affected chromosomal fragments are enriched and preferably sequenced by nanopore sequencing. This protocol was validated in gene repair experiments without intentionally inducing a DNA double strand break. For a 21-nucleotide-long phosphorothioate-modified oligodeoxynucleotide, we compiled a broad array of error-free incorporations, point mutations, indels, and structural rearrangements from actively dividing HEK293-derived cells. Additionally, we demonstrated the usefulness of this approach for primary cells by treating human CD34+ hematopoietic stem and progenitor cells with a 100-nucleotide-long unmodified oligodeoxynucleotide directed against the endogenous CYBB locus. This work should pave the way for future genotoxicity analyses. Concerning genome engineering approaches based on nuclease-induced DNA double-strand breaks, this protocol could aid in detecting the unwanted effects caused by the donor fragments themselves. PMID- 28988717 TI - Where are the innovations in tuberculosis drug discovery? PMID- 28988715 TI - Self-Transducible Bimodal PDX1-FOXP3 Protein Lifts Insulin Secretion and Curbs Autoimmunity, Boosting Tregs in Type 1 Diabetic Mice. AB - Type 1 diabetes (T1D) is characterized by massive destruction of insulin producing beta cells by autoreactive T lymphocytes, arising via defective immune tolerance. Therefore, effective anti-T1D therapeutics should combine autoimmunity preventing and insulin production-restoring properties. We constructed a cell permeable PDX1-FOXP3-TAT fusion protein (FP) composed of two transcription factors: forkhead box P3 (FOXP3), the master regulator of differentiation and functioning of self-tolerance-promoting Tregs, and pancreatic duodenal homeobox-1 (PDX1), the crucial factor supporting beta cell development and maintenance. The FP was tested in vitro and in a non-obese diabetic mouse T1D model. In vitro, FP converted naive CD4+ T cells into a functional "Treg-like" subset, which suppressed cytokine secretion, downregulated antigen-specific responses, and curbed viability of diabetogenic effector cells. In hepatic stem-like cells, FP potentiated endocrine transdifferentiation, inducing expression of Insulin2 and other beta lineage-specific genes. In vivo, FP administration to chronically diabetic mice triggered (1) a significant elevation of insulin and C-peptide levels, (2) the formation of insulin-containing cell clusters in livers, and (3) a systemic anti-inflammatory shift (higher Foxp3+CD4+CD25+ T cell frequencies, elevated rates of IL-10-producing cells, and reduced rates of IFN-gamma-secreting cells). Overall, in accordance with its design, PDX1-FOXP3-TAT FP delivered both Treg-stabilizing anti-autoimmune and de novo insulin-producing effects, proving its anti-T1D therapeutic potential. PMID- 28988716 TI - Evaluation of GalNAc-siRNA Conjugate Activity in Pre-clinical Animal Models with Reduced Asialoglycoprotein Receptor Expression. AB - The hepatocyte-specific asialoglycoprotein receptor (ASGPR) is an ideal candidate for targeted drug delivery to the liver due to its high capacity for substrate clearance from circulation together with its well-conserved expression and function across species. The development of GalNAc-siRNA conjugates, in which a synthetic triantennary N-acetylgalactosamine-based ligand is conjugated to chemically modified siRNA, has enabled efficient, ASGPR-mediated delivery to hepatocytes. To investigate the potential impact of variations in receptor expression on the efficiency of GalNAc-siRNA conjugate delivery, we evaluated the pharmacokinetics and pharmacodynamics of GalNAc-siRNA conjugates in multiple pre clinical models with reduced receptor expression. Despite greater than 50% reduction in ASGPR levels, GalNAc conjugate activity was retained, suggesting that the remaining receptor capacity was sufficient to mediate efficient uptake of potent GalNAc-siRNAs at pharmacologically relevant dose levels. Collectively, our data support a broad application of the GalNAc-siRNA technology for hepatic targeting, including disease states where ASGPR expression may be reduced. PMID- 28988718 TI - An acute hospital admission greatly increases one year mortality - Getting sick and ending up in hospital is bad for you: A multicentre retrospective cohort study. AB - BACKGROUND: For most of the population a serious acute illness that require an emergency admission to hospital is a rare "once in a life time" event. This paper reports the one year mortality of patients admitted to hospital as acute emergencies compared to the general population. METHOD: This is a post-hoc retrospective multicentre cohort study of acutely admitted patients from October 2008 to December 2013 aged 40 or higher. It compares the observed one-year mortality of both acute medical and surgical patients with the overall mortality in the general population at comparable age bands. RESULTS: We included 18,375 patients and 4037 (22.0%) died within one year. For all age groups the one year mortality of those admitted to hospital for acute illness was markedly greater than for the general population. Although the odds ratio of death was highest in younger patients (e.g. odds ratio >20 for 40year olds), the absolute risk of death was greatest in the elderly (e.g. 20% mortality rate for men admitted to hospital over 65years of age, compared to 1.7% for the general population). DISCUSSION: Admission to hospital for an acute illness is associated with a greatly increased risk of death within a year and for many elderly patients may be a seminal event. PMID- 28988719 TI - A young patient with back pain. PMID- 28988720 TI - Dilation of duodenum, stomach and esophagus in a patient with weight loss. PMID- 28988721 TI - Erratum. PMID- 28988722 TI - Erratum. PMID- 28988723 TI - PCSK9 inhibitor therapy in homozygous familial defective apolipoprotein B-100 due to APOB R3500Q: A case report. AB - Identification of a patient homozygous for familial defective apolipoprotein B 100(FDB) and successful treatment with PCSK9 inhibition. PMID- 28988724 TI - Antiarrhythmics in Cardiac Arrest: A Systematic Review and Meta-Analysis. AB - INTRODUCTION: It is widely accepted that antiarrhythmics play a role in cardiopulmonary resuscitation (CPR) universally, but the absolute benefit of antiarrhythmic use and the drug of choice in advanced life support remains controversial. AIM: To perform a thorough, in-depth review and analysis of current literature to assess the efficacy of antiarrhythmics in advanced life support. MATERIAL AND METHODS: Two authors systematically searched through multiple bibliographic databases including CINAHL, SCOPUS, PubMed, Web of Science, Medline(Ovid) and the Cochrane Clinical Trials Registry. To be included studies had to compare an antiarrhythmic to either a control group, placebo or another antiarrhythmic in adult cardiac arrests. These studies were independently screened for outcomes in cardiac arrest assessing the effect of antiarrhythmics on return of spontaneous circulation (ROSC), survival and neurological outcomes. Data was extracted independently, compared for homogeneity and level of evidence was evaluated using the Cochrane Collaboration's tool for assessing the risk of bias. The Mantel-Haenszel (M-H) random effects model was used and heterogeneity was assessed using the I2 statistic. RESULTS AND DISCUSSION: The search of the literature yielded 30 studies, including 39,914 patients. Eight antiarrhythmic agents were identified. Amiodarone and lidocaine, the two most commonly used agents, showed no significant effect on any outcome either against placebo or each other. Small low quality studies showed benefits in isolated outcomes with esmolol and bretylium against placebo. The only significant benefit of one antiarrhythmic over another was demonstrated with nifekalant over lidocaine for survival to admission (p=0.003). On sensitivity analysis of a small number of high quality level one RCTs, both amiodarone and lidocaine had a significant increase in survival to admission, with no effect on survival to discharge. CONCLUSIONS: This systematic review and meta-analysis suggests that, based on current literature and data, there has been no conclusive evidence that any antiarrhythmic agents improve rates of ROSC, survival to admission, survival to discharge or neurological outcomes. Given the side effects of some of these agents, we recommend further research into their utility in current cardiopulmonary resuscitation guidelines. PMID- 28988725 TI - Prevention of preterm birth: Novel interventions for the cervix. AB - Preterm birth is the leading cause of neonatal mortality and morbidity worldwide. Spontaneous preterm birth is a complex, multifactorial condition in which cervical dysfunction plays an important role in some women. Current treatment options for cervical dysfunction include cerclage and supplemental progesterone. In addition, cervical pessary is being studied in research protocols. However, cerclage, supplemental progesterone and cervical pessary have well known limitations and there is a strong need for alternate treatment options. In this review, we discuss two novel interventions to treat cervical dysfunction: (1) injectable, silk protein-based biomaterials for cervical tissue augmentation (injectable cerclage) and (2) a patient-specific pessary. Three-dimensional computer simulation of the cervix is performed to provide a biomechanical rationale for the interventions. Further development of these novel interventions could lead to new treatment options for women with cervical dysfunction. PMID- 28988726 TI - Placenta-specific gene manipulation using lentiviral vector and its application. AB - The placenta is an essential organ for embryo development in the uterus of eutherian mammals. Large contributions in unveiling molecular mechanisms and physiological functions underlying placental formation were made by analyzing mutant and transgenic animals. However, it had been difficult to elucidate whether the placental defects observed in such animals originate from the placenta itself or from the fetus, as both placental and fetal genomes are modified. Therefore strategies to modify the placental genome without affecting the "fetal genome" had been needed. Through the ingenious use of lentiviral (LV) vectors, placenta-specific modification is now possible. Lentivirus is a genus of retroviruses that use reverse-transcriptase to convert its single-strand RNA genome to double-strand DNA and integrate into the host genome. Previous studies showed that when LV vectors were used to transduce embryos at the 2-cell stage, the viral genome is systemically introduced into host genome. Interestingly, by delaying the timing of transduction to the blastocyst stage, the transgene is expressed specifically in the placenta as a consequence of trophectoderm-specific viral transduction. This review summarizes the development of the LV vector mediated placenta-specific gene manipulation technology and its application in placental research over the past decade. A perspective for future application of LV vectors to further placenta research, especially in combination with next generation genome editing technologies, is also presented. PMID- 28988727 TI - The mycobiome: Role in health and disease, and as a potential probiotic target in gastrointestinal disease. AB - The human gastrointestinal (GI) tract is home to trillions of microorganisms, some beneficial and others potentially harmful. Recent advances in science have allowed us to identify the multitude of organisms inhabiting the GI tract and parse out those that play a role in inflammatory bowel disease (IBD). Unfortunately, most research has focused on studying only the bacteria while ,overlooking a key player, fungus. In order to address this issue, we have focused our efforts on studying the fungal community in the GI tract known as the mycobiome. We found that patients with Crohn's disease (CD) tend to have much higher levels of the fungus Candida tropicalis compared to their healthy family members, as well as two bacteria, Escherichia coli and Serratia marcescens. Furthermore, we showed that these three organisms worked together to form robust biofilms capable of exacerbating intestinal inflammation. Herein, we discuss the role of the mycobiome in health and disease, and highlight the importance of maintaining balance of the GI microbiota. Additionally, taking into consideration recent next generation sequencing data, we provide insight into potentially new therapeutic approaches in the treatment of IBD through the use of antifungals and/or probiotics aimed at establishing and maintaining a healthy balance of the GI total microbial community including fungi and bacteria. PMID- 28988728 TI - Vertical locking of the metacarpophalangeal joint of the little finger: A case report. AB - Locking of the metacarpophalangeal (MCP) joint is commonly caused by hyperextension of the thumb or moderate flexion of the index or middle finger. We report a rare case of vertical locking of the MCP joint of the little finger in a 16-year old female after blunt trauma to the little finger. The MCP joint was locked when positioned at approximately 90-degree-flexion and could not extend actively or passively. A manual reduction was easily achieved and no immobilization was applied. Vertical locking of the MCP joint can be easily reduced, and immobilization is unnecessary after reduction. Correct diagnosis prior to reduction and differentiation from other types of locking are essential to prevent overtreatment. PMID- 28988730 TI - Erratum to "Orthopedics research output from China, USA, UK, Japan, Germany and France: A 10-year survey of the literature" [Orthop. Traumatol. Surg. Res. 102 (2016) 939-945]. PMID- 28988729 TI - Allergic reactions to antivenom in a patient bitten twice by the same snake within a month: A rare case report and literature review. AB - Antivenom is the most effective method currently available for the treatment of poisonous snake bite. Allergic reactions to antivenom have been reported in the past. Here we shared a case of allergic reactions to antivenom in an old male patient who was bitten twice by the same snake (probably same one) at the same biting site within a month whereas the patient did not show any allergic disorder in the first bitten. Envenomations twice in a short period time by the same kind of snake are very rare. Physician should be alert to the occurrence of allergic reactions in treating this type of patients with antivenom. The skin allergy test has a certain value in predicting the allergic response before the second use of antivenom. Desensitization may reduce the incidence of allergic reactions, but this is insufficient. Rather than non-IgE-mediated immediate hypersensitivity, patients receiving the second treatment of antivenom may develop IgE-mediated immediate hypersensitivity. Once happened, the antivenom treatment should be stopped promptly and anti-allergy treatment should be given immediately. PMID- 28988731 TI - The Australian Royal Commission into Institutional Responses to Child Sexual Abuse and the Roman Catholic Church. AB - The Australian Royal Commission into Institutional Responses to Child Sexual Abuse received more reports of sexual abuse of minors from victims of personnel from the Catholic Church than from any other source. It looked beyond the circumstances of the individual reports, to the response of Church leaders. It then took the inquiry to the more fundamental issue of the elements of the Church's structure and its unique culture that enabled sexual abuse and supported the hierarchy's counter-productive responses. This commentary looks at the structural and cultural aspects of the institutional Church most directly connected to sexual abuse by clerics and the ensuing cover-up and it examines their theological and historical foundations. The reality that sexual abuse by clerics was not only known but condoned and covered up cannot be justified but it can be explained in great part by the Church's justification for its own structure and the role of its clerics. PMID- 28988732 TI - Rupture of an Occult Intracranial Mycotic Aneurysm after Intravenous Thrombolysis with Recombinant Tissue Plasminogen Activator for Acute Ischemic Stroke. AB - BACKGROUND: The treatment of acute ischemic stroke with recombinant tissue plasminogen activator (rtPA) has become the mainstay of treatment, but its use carries a risk of subsequent intracranial hemorrhage (ICH). Guidelines have been developed to aid in the selection of the appropriate candidates to treat with rtPA to reduce this risk. We present a case of a stroke patient who was an appropriate candidate and was treated with rtPA who experienced a fatal subarachnoid hemorrhage due to a ruptured mycotic aneurysm (MA). CASE REPORT: A 51-year-old man presented to the Emergency Department with acute neurological symptoms concerning for acute ischemic stroke. His National Institutes of Health Stroke Scale score was 22. Emergent noncontrast head computed tomography (CT) revealed no sign of hemorrhage. The patient received intravenous rtPA, and about 1 h after the infusion was started, he had an acute deterioration in his mental status. Repeat CT scan revealed a large subarachnoid hemorrhage, and the patient was later found to have two intracranial aneurysms consistent with a ruptured MA that were related to his remote history of infective endocarditis. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: The majority of MAs are caused by infective endocarditis. In patients presenting with acute neurologic symptoms with a history of infective endocarditis, emergency physicians should strongly consider obtaining CT angiography to rule out MA prior to treating presumed acute ischemic stroke with rtPA. PMID- 28988733 TI - Delayed Dermatitis Following Injury Caused by Coral. PMID- 28988734 TI - Intractable Nausea Due to the Area Postrema Syndrome of Neuromyelitis Optica: An Uncommon Cause of a Common Symptom. AB - BACKGROUND: Nausea and vomiting are common emergency department (ED) complaints. Neuromyelitis optica, a demyelinating disorder, has a predilection for the area postrema, the central nausea and vomiting center. Demyelinating lesions in this region cause intractable nausea and vomiting. CASE REPORT: We present a case of area postrema syndrome due to neuromyelitis optica in a 34-year-old woman who was seen in several EDs before the appropriate diagnosis was made. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Nausea and vomiting are complaints that commonly bring people to the ED, thus, emergency physicians are likely to be the first to encounter and diagnose the area postrema syndrome. PMID- 28988736 TI - Response to Letter to the Editor. PMID- 28988735 TI - Identifying Advanced Illness Patients in the Emergency Department and Having Goals-of-Care Discussions to Assist with Early Hospice Referral. AB - BACKGROUND: The emergency department (ED) is often where patients with advanced illness (AI) present when faced with an acute deterioration in their disease. OBJECTIVES: To investigate the effectiveness of our AI Management program in the ED on key outcomes. METHODS: We conducted a pre-post study with a retrospective chart review with ED patients at an academic, tertiary care hospital in the New York metropolitan area. We assessed changes from baseline to intervention period on percent of patients identified in the ED with AI, percent who received an ED led goals-of-care (GOC) discussion, and percent referred to hospice from the ED. We used the Fisher's exact test or the Mann-Whitney test to compare groups, as appropriate. RESULTS: Our sample consisted of 82 patients (21 baseline and 61 intervention). Patients in the baseline period had a median age of 75 years, with 61.9% being female, whereas those in the intervention period had a median age of 83 years, with 67.2% being female. Patients in the intervention, compared with baseline, were significantly more likely to be identified as having AI in the ED (90.2% vs. 0.0%; p < 0.0001), to receive an ED-led GOC conversation (83.6% vs. 0.0%; p < 0.0001), and to be discharged to home hospice (39.3% vs. 0.0%; p < 0.0001). CONCLUSIONS: The ED provides a critical opportunity to identify AI patients, have ED-led GOC discussions, and refer appropriate patients to hospice. PMID- 28988737 TI - Hematometrocolpos Disguised as Abdominal Pain. AB - BACKGROUND: Hematometrocolpos caused by an imperforate hymen is a common form of vaginal outflow obstruction. This is a rare pediatric anomaly that can present with atypical or vague symptomatology, such as abdominal pain or constipation or urinary retention in the setting of amenorrhea. It is essential to obtain a gynecologic history and inquire about menstrual cycles to properly evaluate a young female with such a common complaint as abdominal pain. Failure to perform a gynecologic examination in the emergency department setting may delay diagnosis and appropriate care for this rare condition, which can lead to serious complications. CASE REPORT: This case describes a 12-year-old female who presented to the emergency department with a complaint of abdominal pain and urinary symptoms. Because of the severity of the patient's pain on abdominal examination, we obtained a computed tomography scan of her abdomen and pelvis, which showed findings consistent with hematometrocolpos. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Obstruction of the female genital outflow tract is a rare occurrence. Because abdominal pain is such a common complaint, not only in the pediatric emergency department but also in the outpatient setting, the diagnosis of hematometrocolpos may easily go undiagnosed for months or even years. Obtaining a complete gynecologic history is key when evaluating young females with abdominal pain or urinary retention. Early detection and timely management can prevent serious complications and long-term sequelae. This patient had a successful outcome and early surgical management of her hematometrocolpos which was caused by an imperforate hymen. PMID- 28988738 TI - Tripartite Fracture of the Ulnar Sesamoid Bone of the Thumb. PMID- 28988739 TI - A Tale of Black Eschar in a Returning Traveller. AB - BACKGROUND: African tick-bite fever is an increasingly common cause for fever in the returning traveller. It needs to be considered in the febrile returning traveller with a characteristic rash: a black eschar. CASE REPORT: We describe a 51-year-old man returning from South Africa who presented to our emergency department with fever, headache, myalgia, and chills. On careful history and skin examination, a black eschar was found on the patient's left lateral shoulder, pointing toward a diagnosis of African tick-bite fever. The patient was treated with doxycycline and rapidly improved. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: In the emergency department, the diagnosis of African tick-bite fever is often overlooked in the pursuit of ruling out other travel-related illnesses, such as malaria. A thorough history, a complete physical examination, and a high level of suspicion are essential to the timely diagnosis and treatment of African tick-bite fever in the returning traveller. PMID- 28988740 TI - Health Care Usage and Suicide Risk Screening within 1 Year of Suicide Death. AB - BACKGROUND: Research indicates patients often seek medical care within 1 year of suicide. Health care encounters are a crucial opportunity for health professionals to identify patients at highest risk and provide preventative services. OBJECTIVE: Study aims were to determine the characteristics of persons seeking health care within 12 months of suicide death and evaluate suicide risk screening (SRS) frequency in the emergency department (ED) vs. clinic settings. METHODS: Medical examiner and hospital data of patients who died by suicide from 2007 to 2013 were evaluated. Descriptive analyses included demographics and frequency of ED vs. clinic visits. We also compared SRS before and after implementation of The Joint Commission's recommendation to assess suicide risk. RESULTS: The 224 deceased patients were primarily single white males (mean age 67 years). Mental health issues, substance abuse, and prior suicide attempts were present alone or in combination in 74%. Visits were primarily behavioral health or substance abuse problems in the ED, and medical issues in the clinic. After implementation of universal SRS in the ED, screening increased from 39% to 92%. Among patients screened in the ED, 73% (37 of 51) screened negative for suicide risk. CONCLUSIONS: Universal SRS increased the number of people screened in the ED. However, negative SRS may not equate to reduced risk for future suicide within 1 year. Future studies might investigate targeted screening of individuals with known suicide risk factors, as well as alternatives to patient self-report of intent to self-harm for patients with mental health or substance abuse problems. PMID- 28988741 TI - Smad7 alleviates glomerular mesangial cell proliferation via the ROS-NF-kappaB pathway. AB - OBJECTIVE: The aim of this study was to demonstrate that altered gene expression of Smad7regulated NF-kappaB expression and ROS production on Ang II (Angiotensin II)-induced rat glomerular mesangial cell (GMC) proliferation. METHODS: pAdTrack CMV-Smad7 was transduced into rat GMC by adeno-transduction using an ADV (adenovirus)-mediated vector in vivo. Diphenylene iodonium chloride (DPI) pre treated GMC, and blocked ROS generation as determined by DCFH-DA method. Altered expressions of IkappaBalpha and p65 were monitored by Western blot analysis and immunofluorescence. GMC proliferation was tested by the Cell Counting Kit-8 assay. Apoptosis of GMC was detected by flow cytometric analysis. RESULTS: Over expression of Smad7 dampened the ability of Ang II to promote ROS synthesis and inhibited the ability of Ang II to decrease functional expression of IkappaBalpha. Moreover, Smad7 increased nuclear IkappaBalpha expression. Smad7 did not significantly influence the capacity of Ang II to increase protein expression of NF-kappaB p65. However, immunofluorescence analysis showed that Smad7 reduced nuclear NF-kappaB p65 level. Further, over-expression of Smad7 promoted GMC apoptosis by inhibiting NF-kappaB activation, which alleviated the Ang II-promoted proliferation of GMC. CONCLUSIONS: Smad7 influenced NF-kappaB expression by regulating ROS generation, and induced GMC apoptosis to counter the Ang II-promoted proliferation. PMID- 28988742 TI - Chimeric antigen-receptor T-cell therapy for hematological malignancies and solid tumors: Clinical data to date, current limitations and perspectives. AB - Progress in our understanding of basic immunology along with the advent of bioengineering technologies have made possible the production of human T-cells expressing Chimeric Antigen Receptors (CAR T-cells). These CAR T-cells are designed to target specific antigens presented by cancer cells. Once CARs are bound to these antigens, CAR T-cells get activated and can initiate potent anti tumor effects. We will here overview the bioengineering advances which made possible the clinical application of CAR T-cell therapy. We will review the data to date regarding anti-CD19 CAR T-cell therapy for acute lymphoblastic leukemia, non-Hodgkin lymphomas, and chronic lymphocytic leukemia. Besides CD19, CAR T cells directed against the B-cell maturation antigen have also shown encouraging results to treat patients with refractory multiple myeloma. The more limited body of clinical research in the field of solid tumors will also be reviewed. Moreover, we will elaborate on the main toxicities of limitations of CAR T-cell therapy, namely cytokine release syndrome and neurotoxicity. While enjoying an undeniable hype, CAR T-cell therapy bears significant limitations. We will conclude by exposing the possible approaches to make CAR T-cells safer and more efficient beyond the CD19 target. PMID- 28988743 TI - Fludarabine-based reduced intensity regimen for matched related donor hematopoietic stem cell transplantation in acquired severe aplastic anemia. AB - Different conditioning regimens have been evaluated in matched-related donor allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acquired severe aplastic anemia (SAA) with varying results. In this manuscript, we report our experience with fludarabine (120mg/m2), very low dose cyclophosphamide (1200mg/m2) and antithymocyte globulin (7.5mg/kg). Low dose total body irradiation (2Gy) was added to the conditioning regimen for patients older than 15 years. Nineteen patients (median age 23years) underwent transplant between 2008 and 2015. The majority (89%) were younger than 40 years. Stem cell source was BM (n=11) or PBSC (n=8). GvHD prophylaxis consisted of cyclosporine and either a short course of methotrexate (n=9) or mycophenolate mofetil (n=10). Eighteen (94.7%) patients achieved sustained engraftment. The median times to neutrophil and platelet engraftments were 19 (range: 14-34) and 17.1 (range: 12 25) days, respectively. The day-30 cumulative incidence of neutrophil and platelet engraftment was 89.4% and 94.7%, respectively. No secondary graft rejection was observed. The 1-year cumulative incidence of aGvHD (grade II-IV) and cGvHD was 11.7% and 0%, respectively. The 2-year GvHD-free survival rate was 78.6% (95% CI: 52.5-91.4%). Fludarabine-based reduced intensity regimen for MRD allo-HSCT in SAA compares favorably to other available regimens. This regimen deserves further investigations with larger cohort of patients. PMID- 28988744 TI - Management of Endometriosis: Toward Value-Based, Cost-Effective, Affordable Care. AB - Endometriosis management seems to be influenced by outcome-independent biomedical, pharmacological, and technological developments. The propensity towards doing more affects several aspects of care, sometimes translating into proposals that are not based on sound epidemiological principles and robust evidence. Different stakeholders share the interest for doing more testing and using novel and costly drugs or devices in patients with endometriosis. Although some women may benefit from such an approach, the majority do not, and some may be harmed. Moreover, an uncontrolled increase in expenditures for endometriosis management without demonstrated and proportional health benefits would waste the finite resources of national health care services and would risk cost-related non adherence. Cost-effectiveness analyses should be systematically pre-planned in future trials on endometriosis, and the concept of "value" of medical interventions should guide investigators and health care policymakers. Reducing low-value care, financial toxicity, and the burden of treatment is respectful not only of endometriosis patients, but also of the entire society. Whenever possible, long-term therapeutic strategies should be tailored to each woman's needs, and high-value tests and treatments should be chosen based on her priorities and preferences. Moreover, listening to patients, understanding their concerns, avoiding disease labelling, explaining plainly what is known and what is unknown, and giving constant reassurance and encouragement may be exceedingly important for the successful management of endometriosis and may change the patient's perception of her clinical condition. Physician empathy has no untoward effects, does not cause harms, and may determine whether a woman successfully copes or desperately struggles with her disease during reproductive life. PMID- 28988745 TI - Moving Beyond Uterotonics for the Treatment of Postpartum Hemorrhage: Lessons From the WOMAN Study. PMID- 28988746 TI - Sedative and physiologic effects of low-dose intramuscular alfaxalone in dogs. AB - OBJECTIVE: To describe the sedative and physiologic effects of two doses of alfaxalone administered intramuscularly in dogs. STUDY DESIGN: Randomized, blinded, crossover experimental trial. ANIMALS: Ten adult mixed-breed dogs. METHODS: Dogs were assigned randomly to be administered one of three intramuscular injections [saline 0.1 mL kg-1 (S), alfaxalone 1 mg kg-1 (A1) or alfaxalone 2 mg kg-1 (A2)] on three occasions. Heart rate (HR), respiratory rate (fR) and sedation score were assessed before injection (T0) and at 5 (T5), 10 (T10), 15 (T15), 20 (T20), 30 (T30), 45 (T45) and 60 (T60) minutes postinjection. Rectal temperature was determined at T0 and T60. Adverse events occurring between the time of injection and T60 were recorded. RESULTS: Sedation scores were higher in group A2 at T15 and T30 compared with group S. There were no additional differences between groups in sedation score. The A2 group had higher sedation scores at T15, T20 and T30 compared with T0. The A1 group had higher sedation scores at T10 and T30 compared with T0. Temperature was lower in groups A1 and A2 compared with S at T60, but was not clinically significant. There were no differences between or within groups in HR or fR. Adverse effects were observed in both A1 and A2 groups. These included ataxia (17/20), auditory hyperesthesia (5/20), visual disturbance (5/20), pacing (4/20) and tremor (3/20). CONCLUSIONS AND CLINICAL RELEVANCE: While alfaxalone at 2 mg kg-1 intramuscularly resulted in greater median sedation scores compared with saline, the range was high and adverse effects frequent. Neither protocol alone can be recommended for providing sedation in healthy dogs. PMID- 28988747 TI - Structural Insights into VLR Fine Specificity for Blood Group Carbohydrates. AB - High-quality reagents to study and detect glycans with high specificity for research and clinical applications are severely lacking. Here, we structurally and functionally characterize several variable lymphocyte receptor (VLR)-based antibodies from lampreys immunized with O erythrocytes that specifically recognize the blood group H-trisaccharide type II antigen. Glycan microarray analysis and biophysical data reveal that these VLRs exhibit greater specificity for H-trisaccharide compared with the plant lectin UEA-1, which is widely used in blood typing. Among these antibodies, O13 exhibits superior specificity for H trisaccharide, the basis for which is revealed by comparative analysis of high resolution VLR:glycan crystal structures. Using a structure-guided approach, we designed an O13 mutant with further enhanced specificity for H-trisaccharide. These insights into glycan recognition by VLRs suggest that lampreys can produce highly specific glycan antibodies, and are a valuable resource for the production of next-generation glycan reagents for biological and biomedical research and as diagnostics and therapeutics. PMID- 28988749 TI - Peptide therapeutics from venom: Current status and potential. AB - Peptides are recognized as being highly selective, potent and relatively safe as potential therapeutics. Peptides isolated from the venom of different animals satisfy most of these criteria with the possible exception of safety, but when isolated as single compounds and used at appropriate concentrations, venom derived peptides can become useful drugs. Although the number of venom-derived peptides that have successfully progressed to the clinic is currently limited, the prospects for venom-derived peptides look very optimistic. As proteomic and transcriptomic approaches continue to identify new sequences, the potential of venom-derived peptides to find applications as therapeutics, cosmetics and insecticides grows accordingly. PMID- 28988748 TI - Structural and Functional Implications of Human Transforming Growth Factor beta Induced Protein, TGFBIp, in Corneal Dystrophies. AB - A major cause of visual impairment, corneal dystrophies result from accumulation of protein deposits in the cornea. One of the proteins involved is transforming growth factor beta-induced protein (TGFBIp), an extracellular matrix component that interacts with integrins but also produces corneal deposits when mutated. Human TGFBIp is a multi-domain 683-residue protein, which contains one CROPT domain and four FAS1 domains. Its structure spans ~120 A and reveals that vicinal domains FAS1-1/FAS1-2 and FAS1-3/FAS1-4 tightly interact in an equivalent manner. The FAS1 domains are sandwiches of two orthogonal four-stranded beta sheets decorated with two three-helix insertions. The N-terminal FAS1 dimer forms a compact moiety with the structurally novel CROPT domain, which is a five-stranded all-beta cysteine-knot solely found in TGFBIp and periostin. The overall TGFBIp architecture discloses regions for integrin binding and that most dystrophic mutations cluster at both molecule ends, within domains FAS1-1 and FAS1-4. PMID- 28988750 TI - Design, synthesis and biological evaluation of 2-phenylquinoline-4-carboxamide derivatives as a new class of tubulin polymerization inhibitors. AB - A novel series of 2-phenylquinoline-4-carboxamide derivatives was synthesized, characterized and evaluated for its antiproliferative activity against five cancer cell lines, Hela, SK-OV-3, HCT116, A549 and MDA-MB-468, and a normal human fetal lung fibroblastic cell line, MRC-5. Among them, compound 7b displayed potent cytotoxic activity in vitro against SK-OV-3 and HCT116 cell lines with IC50 values of 0.5 and 0.2MUM, respectively. In general, the antiproliferative activity was correlated with the binding property of the colchicine binding site and inhibitory effect on tubulin polymerization. In addition, immunofluorescence and flow cytometry analysis revealed that selected compounds caused disruption of the mitotic spindle assembly and G2/M phase arrest of the cell cycle, which correlated with proliferation inhibitory activity. Molecular docking analysis demonstrated the interaction of 7b at the colchicine binding site of tubulin. These results indicate these compounds are promising inhibitors of tubulin polymerization for the potent treatment of cancer. PMID- 28988751 TI - Synthesis, computational studies and enzyme inhibitory kinetics of substituted methyl[2-(4-dimethylamino-benzylidene)-hydrazono)-4-oxo-thiazolidin-5 ylidene]acetates as mushroom tyrosinase inhibitors. AB - The present article describes the synthesis and enzyme inhibitory kinetics of methyl[2-(arylmethylene-hydrazono)-4-oxo-thiazolidin-5-ylidene]acetates 5a-j as mushroom tyrosinase inhibitors. The title compounds were synthesized via cyclocondensation of thiosemicarbazones 3a-j with dimethyl but-2-ynedioate (DMAD) 4 in good yields under solvent-free conditions. The synthesized compounds were evaluated for their potential to inhibit the activity of mushroom tyrosinase. It was unveiled that compounds 5i showed excellent enzyme inhibitory activity with IC50 3.17uM while IC50 of standard kojic acid is 15.91uM. The presence of heterocyclic pyridine ring in compound 5i play important role in enzyme inhibitory activity as rest of the functional groups are common in all synthesized compounds. The enzyme inhibitory kinetics of the most potent derivative 5i determined by Lineweaver-Burk plots and Dixon plots showed that it is non-competitive inhibitor with Ki value 1.5uM. It was further investigated that the wet lab results are in good agreement with the computational results. The molecular docking of the synthesized compounds was performed against tyrosinase protein (PDBID 2Y9X) to delineate ligand-protein interactions at molecular level. The docking results showed that the major interacting residues are His244, His85, His263, Val 283, His 296, Asn260, Val248, His260, His261 and Phe264 which are located in active binding site of the protein. The molecular modeling demonstrates that the oxygen atom of the compound 5i coordinated with the key residues in the active site of mushroom tyrosinase contribute significantly against inhibitory ability and diminishing the human melanin synthesis. These results evident that compound 5i is a lead structure in developing most potent mushroom tyrosinase inhibitors. PMID- 28988752 TI - The Gift of Life: New Opportunities from Renal Transplantation. PMID- 28988753 TI - A Biopsy-based 17-gene Genomic Prostate Score as a Predictor of Metastases and Prostate Cancer Death in Surgically Treated Men with Clinically Localized Disease. AB - BACKGROUND: A 17-gene biopsy-based reverse transcription polymerase chain reaction assay, which provides a Genomic Prostate Score (GPS-scale 0-100), has been validated as an independent predictor of adverse pathology and biochemical recurrence after radical prostatectomy (RP) in men with low- and intermediate risk prostate cancer (PCa). OBJECTIVE: To evaluate GPS as a predictor of PCa metastasis and PCa-specific death (PCD) in a large cohort of men with localized PCa and long-term follow-up. DESIGN, SETTING, AND PARTICIPANTS: A retrospective study using a stratified cohort sampling design was performed in a cohort of men treated with RP within Kaiser Permanente Northern California. RNA from archival diagnostic biopsies was assayed to generate GPS results. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We assessed the association between GPS and time to metastasis and PCD in prespecified uni- and multivariable statistical analyses, based on Cox proportional hazard models accounting for sampling weights. RESULTS AND LIMITATIONS: The final study population consisted of 279 men with low-, intermediate-, and high-risk PCa between 1995 and 2010 (median follow-up 9.8 yr), and included 64 PCD and 79 metastases. Valid GPS results were obtained for 259 (93%). In univariable analysis, GPS was strongly associated with time to PCD, hazard ratio (HR)/20 GPS units=3.23 (95% confidence interval [CI] 1.84-5.65; p<0.001), and time to metastasis, HR/20 units=2.75 (95% CI 1.63-4.63; p<0.001). The association between GPS and both end points remained significant after adjusting for National Comprehensive Cancer Network, American Urological Association, and Cancer of the Prostate Risk Assessment (CAPRA) risks (p<0.001). No patient with low- or intermediate-risk disease and a GPS of<20 developed metastases or PCD (n=31). In receiver operating characteristic analysis of PCD at 10 yr, GPS improved the c-statistic from 0.78 (CAPRA alone) to 0.84 (GPS+CAPRA; p<0.001). A limitation of the study was that patients were treated during an era when definitive treatment was standard of care with little adoption of active surveillance. CONCLUSIONS: GPS is a strong independent predictor of long-term outcomes in clinically localized PCa in men treated with RP and may improve risk stratification for men with newly diagnosed disease. PATIENT SUMMARY: Many prostate cancers are slow growing and unlikely to spread or threaten a man's life, while others are more aggressive and require treatment. Increasingly, doctors are using new molecular tests, such as the17-gene Genomic Prostate Score (GPS), which can be performed at the time of initial diagnosis to help determine how aggressive a given patient's cancer may be. In this study, performed in a large community-based healthcare network, GPS was shown to be a strong predictor as to whether a man's prostate cancer will spread and threaten his life after surgery, providing information that may help patients and their doctors decide on the best course of management of their disease. PMID- 28988754 TI - [Lens induced glaucoma: Report of 60 cases]. PMID- 28988755 TI - A model of an inflammatory bowel disease population-based registry: The Forli experience (1993-2013). AB - BACKGROUND AND AIMS: The article presents a population-based registry designed to estimate incidence and prevalence of inflammatory bowel disease (IBD) in the area of Forli (north-eastern Italy). METHODS: The registry included all patients with IBD ulcerative colitis (UC) and Crohn's disease (CD) in the Forli area from 1993 to 2013. A data manager matched records from various sources. RESULTS: Seven hundred ninety-one patients were registered during the study period, 564 (71.3%) with UC and 227 (28.7%) with CD. The standardized annual incidence rate for UC was 12.8 per 100,000 females (95% CI 11.1-14.4) and 15.7 per 100,000 males (95% CI 13.9-17.5). That of CD was 7.0 per 100,000 for females (95% CI 5.7-8.3) and 5.4 per 100,000 males (95% CI 4.3-6.4). The prevalence of CD and UC on 1 January 2014 was 109.2 per 100,000 inhabitants (95% CI 94.3-124.2) and 266.4 per 100,000 inhabitants (95% CI 243.4-289.7), respectively. CONCLUSIONS: Although further studies are needed, the data suggest that incidence and prevalence of IBD in Italy are underestimated. PMID- 28988756 TI - Synthesis and in vitro biological evaluation of new pyrimidines as glucagon-like peptide-1 receptor agonists. AB - The therapeutic success of peptide glucagon-like peptide-1 (GLP-1) receptor agonists for the treatment of type 2 diabetes mellitus has inspired discovery efforts aimed at developing orally available small-molecule GLP-1 receptor agonists. In this study, two series of new pyrimidine derivatives were designed and synthesized using an efficient route, and were evaluated in terms of GLP-1 receptor agonist activity. In the first series, novel pyrimidines substituted at positions 2 and 4 with groups varying in size and electronic properties were synthesized in a good yield (78-90%). In the second series, the designed pyrimidine templates included both urea and Schiff base linkers, and these compounds were successfully produced with yields of 77-84%. In vitro experiments with cultured cells showed that compounds 3a and 10a (10-15-10-9M) significantly increased insulin secretion compared to that of the control cells in both the absence and presence of 2.8mM glucose; compound 8b only demonstrated significance in the absence of glucose. These findings represent a valuable starting point for the design and discovery of small-molecule GLP-1 receptor agonists that can be administered orally. PMID- 28988757 TI - Pressure ulcers in critically ill patients - Preventable by non-sedation? A substudy of the NONSEDA-trial. AB - OBJECTIVE: Pressure ulcers still pose a significant clinical challenge to critically ill patients. This study is a substudy of the multicenter NONSEDA trial, where critically ill patients were randomised to sedation or non-sedation during mechanical ventilation. The objective of this substudy was to assess if non-sedation affected the occurrence of pressure ulcers. DESIGN: Retrospective assessment of data from a single NONSEDA-trial site. SETTING: Mixed intensive care unit. OUTCOME MEASURES: The occurrence of pressure ulcers, described by grade and location. RESULTS: 205 patients were included. Patients with pressure ulcers in the two groups were comparable with regards to baseline data. There were 44 ulcers in 32 patients in the sedated group and 31 ulcers in 25 patients in the non-sedated group (p=0.08). 64% of the ulcers in sedated patients were located on sacrum and heels, whereas 68% of the ulcers in non-sedated patients were related to equipment (p=0.03). CONCLUSIONS: Non-sedation did not significantly reduce the number of pressure ulcers. Non-sedation significantly affected the location of ulcers: non-sedated patients mainly had ulcers related to equipment, whereas sedated patients mainly had ulcers on the sacrum and heels. PMID- 28988758 TI - Prevention of spontaneous preterm birth: Guidelines for clinical practice from the French College of Gynaecologists and Obstetricians (CNGOF). PMID- 28988759 TI - Predictors of obesity and overweight in preschoolers: The role of parenting styles and feeding practices. AB - Childhood obesity/overweight (OB/OW) displayed a rapid increase and high prevalence in the last few decades in preschool-aged children, which raised health concerns across the world and motivated researchers to investigate the factors that underlie childhood obesity. The current study examined parenting styles and child-feeding practices as potential predictors for OB/OW in preschool children, controlling for child's temperament, which has been shown to be linked with OB/OW. The sample included 61 normal weight (NW) and 61 obese/overweight (OB/OW) Turkish pre-schoolers (M age = 62.2 months; SD = 7.64, range = 45-80 months). Parenting styles (authoritarian, authoritative), child-feeding practices (restriction, pressure to eat, monitoring), and child's temperament (negative affectivity) were measured with mothers' reports. Results showed that authoritarian parenting and maternal pressure to eat were the two parenting variables that significantly predicted child's weight status; the odds of being OB/OW was 4.71 times higher in children whose mothers used higher authoritarian parenting style, and was 0.44 times lower when mothers pressured their child to eat. These findings suggest that understanding the unique role of different aspects of parenting in the risk of early OB/OW status of children would be important in developing more effective interventions from early years in life. PMID- 28988760 TI - The effects of overnight nutrient intake on hypothalamic inflammation in a free choice diet-induced obesity rat model. AB - Consumption of fat and sugar induces hyperphagia and increases the prevalence of obesity and diabetes type 2. Low-grade inflammation in the hypothalamus, a key brain area involved in the regulation of energy homeostasis is shown to blunt signals of satiety after long term high fat diet. The fact that this mechanism can be activated after a few days of hyperphagia before apparent obesity is present led to our hypothesis that hypothalamic inflammation is induced with fat and sugar consumption. Here, we used a free-choice high-fat high-sugar (fcHFHS) diet-induced obesity model and tested the effects of differential overnight nutrient intake during the final experimental night on markers of hypothalamic inflammation. Male Wistar rats were fed a control diet or fcHFHS diet for one week, and assigned to three different feeding conditions during the final experimental night: 1) fcHFHS-fed, 2) fed a controlled amount of chow diet, or 3) fasted. RT-qPCR and Western blot were utilized to measure hypothalamic gene and protein expression, of cytokines and intermediates of the nuclear factor kappa light-chain-enhancer of activated B cells (NF-kappaB) pathway. Lastly, we investigated the effects of acute fat intake on markers of hypothalamic inflammation in fat-naive rats. fcHFHS-fed rats consumed more calories, increased adipose tissue, and showed elevated expression of hypothalamic inflammation markers (increased phosphorylation of NF-kappaB protein, Nfkbia and Il6 gene expression) compared to chow-fed rats. These effects were evident in rats consuming relative high amounts of fat. Removal of the fat and sugar, or fasting, during the final experimental night ameliorated hypothalamic inflammation. Finally, a positive correlation was observed between overnight acute fat consumption and hypothalamic NF-kappaB phosphorylation in fat-naive rats. Our data indicate that one week of fcHFHS diet, and especially the fat component, promotes hypothalamic inflammation, and removal of the fat and sugar component reverses these detrimental effects. PMID- 28988761 TI - Flavonoids and their derivatives with beta-amyloid aggregation inhibitory activity from the leaves and twigs of Pithecellobium clypearia Benth. AB - To explore potential compounds with marked effect on Alzheimer's disease (AD) in Pithecellobium clypearia Benth., nineteen compounds (1-19) were obtained, including two new flavonoid derivatives, named pithecellobiumol A (1) and pithecellobiumol B (2) and 17 flavonoids (3-19). Their structures were elucidated based on 1D and 2D-NMR spectra as well as HR-ESI-MS data. The absolute configurations of new compounds were assigned by comparing their experimental specific rotation or ECD curves with the calculated data. The inhibitory activity on Abeta aggregation was screened by ThT assay, and compounds 7 (70.7%), 9 (86.5%), 10 (88.4%), 15 (86.1%) and 16 (87.7%) showed outstanding inhibition rate at 20MUM compared to the positive control, curcumin (65.64%). In addition, docking study was performed to initially examine possible molecular mechanisms. Considering the important role of oxidative stress in AD, all the isolated compounds were tested for their H2O2-induced damage in human neuronblastoma SH SY5Y cells. Among them, compound 16 (91.0%) was the most potent candidate in the treatment of AD. PMID- 28988762 TI - A series of novel indazole derivatives of Sirt 1 activator as osteogenic regulators. AB - A series of indazole derivatives were identified as Sirt 1 activators though high throughput screening. Optimization of each substituent on the indazole ring led to the identification of compound 13. Compound 13 appeared to give the best Sirt 1 activity of the compounds tested and also showed osteogenesis activity in a cell assay. Sirt 1 activators are therefore potential candidates for the treatment of osteoporosis. PMID- 28988763 TI - Treatment of Malignant Cutaneous Adnexal Neoplasms. AB - Malignant cutaneous adnexal neoplasms form a group of rare, typically low-grade malignancy carcinomas with follicular, sebaceous, apocrine, or eccrine differentiation or a combination of the first 3 subtypes. Their clinical presentation is usually unremarkable, and biopsy is required to establish the differentiation subtype and the definitive diagnosis. Due to their rarity, no clear consensus has been reached on which treatment is most effective. Mohs micrographic surgery is considered to be the best option to prevent recurrence in the majority of patients. Radiotherapy and chemotherapy have been studied in very few cases and have rarely been shown to be effective. PMID- 28988764 TI - Erratum. PMID- 28988765 TI - Results of a Phase 1/2 Study in Metastatic Renal Cell Carcinoma Patients Treated with a Patient-specific Adjuvant Multi-peptide Vaccine after Resection of Metastases. AB - : Treatment of metastatic renal cell carcinoma comprises metastasectomy+/ systemic medical treatment. Specific immunotherapy after metastasectomy could be a complementary option. In this phase 1/2 study, safety and tolerability of an adjuvant multi-peptide vaccine (UroRCC) after metastasectomy was evaluated together with immune response and efficacy, compared with a contemporary cohort of patients (n=44) treated with metastasectomy only. Nineteen metastatic renal cell carcinoma patients received UroRCC via intradermal or subcutaneous application randomized to immunoadjuvants (granulocyte-macrophage colony stimulating factor or Montanide). Adverse events of UroRCC were mainly grade I and II; frequency of immune response was higher for major histocompatibility complex class II peptides (17/19, 89.5%) than for major histocompatibility complex class I peptides (8/19, 42.1%). Median overall survival was not reached in the UroRCC group (mean: 112.6 mo, 95% confidence interval [CI]: 92.1-133.1) and 58.0 mo (95% CI: 32.7-83.2) in the control cohort (p=0.015). UroRCC was an independent prognosticator of overall survival (hazard ratio=0.19, 95% CI: 0.05 0.69, p=0.012). Adjuvant UroRCC multi-peptide vaccine after metastasectomy was well tolerated, immunogenic, and indicates potential clinical benefit when compared with a contemporary control cohort (NCT02429440). PATIENT SUMMARY: The application of a patient-specific peptide vaccine after complete resection of metastases in metastatic renal cell carcinoma patients resulted in favorable tolerability and outcome. PMID- 28988766 TI - Estimation of the future remnant liver function is a better tool to predict post hepatectomy liver failure than platelet-based liver scores. AB - INTRODUCTION: Recently, there has been increasing interest in the preoperative prediction and prevention of post-hepatectomy liver failure (PHLF). This is a particular concern in colorectal liver metastases (CRLM), when surgery follows potentially hepatotoxic chemotherapy. Platelet-based liver scores (PBLS) such as APRI and FIB-4 are predictive of chemotherapy-associated liver injury (CALI) and PHLF. Estimation of the future liver remnant function (eFLRF) by combining 99mTc Mebrofenin Hepatobiliary Scintigraphy (HBSBSA) with future liver remnant volume ratio (FLRV%), is predictive of PHLF and related mortality. We hypothesized that a HBSBSA based formula was a better predictor for PHLF than PBLS in chemotherapy pretreated CRLM. METHODS: Between 2012 and 2016, 140 patients underwent liver resection for CRLM following systemic therapy. HBSBSA, FLRV%, eFLRF and PBLS were calculated and compared for their value in predicting PHLF. RESULTS: eFLRF and FLRV% had a better predictive value for PHLF than HBSBSA alone and APRI and FIB-4 (AUC = 0.800, 0.843 versus 0.652, 0.635 and 0.658 respectively). In a subgroup analysis (Oxaliplatin all, Oxaliplatin >= 6 cycles, Irinotecan all and Irinotecan >= 6 cycles), eFLRF was the only factor predictive for PHLF in all subgroups (all: p <= 0.05). Prediction of HBSBSA for chemotherapy associated steato hepatitis (CASH) reached almost significance (p = 0.06). FIB-4 was predictive for sinusoidal obstruction syndrome (SOS) (p = 0.011). Only weak correlation was found between HBSBSA and PBLS. CONCLUSION: eFLRF is a better predictor of PHLF than PBLS or HBSBSA alone. PBLS seem to measure other aspects of liver function or damage than HBSBSA. PMID- 28988767 TI - Could lymphadenectomy be avoided in locally advanced cervical cancer patients administered preoperative chemoradiation? A large-scale retrospective study. AB - INTRODUCTION: To identify a subset of cervical cancer (CC) patients administered chemoradiation (CT/RT) plus radical surgery (RS), who can be spared lymphadenectomy, and complications. PATIENTS AND METHODS: 430 Stage IB2-IIB patients without LN involvement at imaging were accrued (March 1996-December 2015) at Gynecologic Oncology Unit of the Catholic University of Rome/Campobasso. CT/RT consisted of pelvic irradiation plus cisplatin based chemotherapy. Objective response was evaluated according to RECIST criteria; radical hysterectomy and pelvic +/- aortic lymphadenectomy was attempted in patients achieving response or stable disease. Surgical morbidity was classified according to the Chassagne grading system. RESULTS: 421 cases underwent RS; metastatic pelvic and aortic LNs were documented in 10.7%, and 8.8% of cases, respectively. In patients without residual tumor in the cervix, there was only 1 case (0.53%) with positive pelvic LNs, and 1 case (2.3%) with metastatic aortic LNs. Analysis of patients according to pre- and post-CT/RT imaging was able to select cases without any metastatic LNs: in patients with negative pelvic LNs at pre- and post CT/RT imaging, none of cases without residual disease in the cervix had metastatic pelvic or aortic LNs. Of 149 early complications, 76 (51.0%) were lymphovascular. The most frequent late complications were lymphovascular (N = 25/61, 41.0%). CONCLUSION: Lymphadenectomy could be avoided in stage IB2-IIB CC patients undergoing preoperative CT/RT, when a careful evaluation of pre- and post-CT/RT imaging and histological assessment of no residual disease in the cervix is made. This approach may avoid lymphadenectomy in 40% of patients with a favourable impact on lymphovascular morbidity. PMID- 28988768 TI - Crosstalk between KCNK3-Mediated Ion Current and Adrenergic Signaling Regulates Adipose Thermogenesis and Obesity. AB - Adrenergic stimulation promotes lipid mobilization and oxidation in brown and beige adipocytes, where the harnessed energy is dissipated as heat in a process known as adaptive thermogenesis. The signaling cascades and energy-dissipating pathways that facilitate thermogenesis have been extensively described, yet little is known about the counterbalancing negative regulatory mechanisms. Here, we identify a two-pore-domain potassium channel, KCNK3, as a built-in rheostat negatively regulating thermogenesis. Kcnk3 is transcriptionally wired into the thermogenic program by PRDM16, a master regulator of thermogenesis. KCNK3 antagonizes norepinephrine-induced membrane depolarization by promoting potassium efflux in brown adipocytes. This limits calcium influx through voltage-dependent calcium channels and dampens adrenergic signaling, thereby attenuating lipolysis and thermogenic respiration. Adipose-specific Kcnk3 knockout mice display increased energy expenditure and are resistant to hypothermia and obesity. These findings uncover a critical K+-Ca2+-adrenergic signaling axis that acts to dampen thermogenesis, maintain tissue homeostasis, and reveal an electrophysiological regulatory mechanism of adipocyte function. PMID- 28988772 TI - Therapeutic hypothermia for hypoxic-ischemic encephalopathy: challenges during transfer and global perspectives. PMID- 28988773 TI - Rifaximin-resistant Clostridium difficile strains isolated from symptomatic patients. AB - BACKGROUND: Rifaximin has been proposed as an alternative treatment for specific cases of Clostridium difficile infection (CDI) and intestinal decontamination. Rifaximin-resistant C. difficile has occasionally been reported. Antibiotic susceptibility testing relies on anaerobic agar dilution (reference method), which is cumbersome and not routinely used. There is no commercial test for detection of resistance to rifaximin. OBJECTIVES: To assess resistance to rifaximin by C. difficile and to evaluate the correlation between the results of the rifampicin E-test and susceptibility to rifaximin. METHODS: We compared the in vitro susceptibility of clinical CDI isolates to rifaximin over a 6-month period using the agar dilution method with susceptibility to rifampicin using the E-test. All isolates were characterized using PCR-ribotyping. Clinical data were recorded prospectively. RESULTS: We recovered 276 consecutive C. difficile isolates and found that 32.2% of episodes were caused by rifaximin-resistant strains. The MICs for rifaximin ranged from <0.0009-256 mg/L, with a geometric mean (GM) of 0.256 mg/L, an MIC50/90 of 0.015/>256 mg/L. Rifaximin and rifampicin MICs were comparable, and all strains classed as resistant by agar dilution were correctly classified as resistant by E-test. The most common ribotypes were 001 (37.2%), 078/126 (14.3%), and 014 (12.0%). Ribotype 001 exhibited the highest MICs for rifaximin. CONCLUSIONS: Resistance to rifaximin was common; resistance rates were higher in ribotype 001 strains. Susceptibility to rifaximin determined by agar dilution correlated with susceptibility to rifampicin determined using the E-test, including rifaximin-resistant strains. Our results suggest that the rifampicin E-test is a valid method for the prediction of rifaximin-resistant C. difficile. PMID- 28988770 TI - Structural Basis for a Safety-Belt Mechanism That Anchors Condensin to Chromosomes. AB - Condensin protein complexes coordinate the formation of mitotic chromosomes and thereby ensure the successful segregation of replicated genomes. Insights into how condensin complexes bind to chromosomes and alter their topology are essential for understanding the molecular principles behind the large-scale chromatin rearrangements that take place during cell divisions. Here, we identify a direct DNA-binding site in the eukaryotic condensin complex, which is formed by its Ycg1Cnd3 HEAT-repeat and Brn1Cnd2 kleisin subunits. DNA co-crystal structures reveal a conserved, positively charged groove that accommodates the DNA double helix. A peptide loop of the kleisin subunit encircles the bound DNA and, like a safety belt, prevents its dissociation. Firm closure of the kleisin loop around DNA is essential for the association of condensin complexes with chromosomes and their DNA-stimulated ATPase activity. Our data suggest a sophisticated molecular basis for anchoring condensin complexes to chromosomes that enables the formation of large-sized chromatin loops. PMID- 28988774 TI - Competition assays between ESBL-producing E. coli and K. pneumoniae isolates collected from Lebanese elderly: An additional cost on fitness. AB - The dissemination of Multi Drug Resistant Organisms (MDROs) is one of the major public health problems addressed nowadays. High fecal carriage rates of MDR Enterobacteriaceae were reported from Lebanese nursing homes. Studies have shown that the acquisition of resistance genes by bacteria might confer a fitness cost detected as a decrease in the frequency of these bacteria as compared to sensitive isolates. In this study, the competitive growth of MDR Enterobacteriaceae isolated from elderly is assessed. Sensitive and ESBL producing Escherichia coli and Klebsiella pneumoniae isolates were identified. Inter-species in-vitro competition assays were conducted in different combinations. ESBL-producing K. pneumoniae presented a fitness cost when competing against sensitive E. coli. On the other hand, resistant E. coli only showed a fitness cost when growing in presence of two sensitive K. pneumoniae isolates. These results suggest that ESBL-production genes in E. coli and K. pneumoniae may confer a fitness cost that leads to the decrease in frequency of these bacteria in interspecies competitions. Culturing bacteria in a medium with more diverse isolates can provide better insights into bacterial competition and resistance dynamics, which can be exploited in the search for alternative therapeutic approaches towards the colonization of resistant bacteria. PMID- 28988771 TI - EGFR Ligands Differentially Stabilize Receptor Dimers to Specify Signaling Kinetics. AB - Epidermal growth factor receptor (EGFR) regulates many crucial cellular programs, with seven different activating ligands shaping cell signaling in distinct ways. Using crystallography and other approaches, we show how the EGFR ligands epiregulin (EREG) and epigen (EPGN) stabilize different dimeric conformations of the EGFR extracellular region. As a consequence, EREG or EPGN induce less stable EGFR dimers than EGF-making them partial agonists of EGFR dimerization. Unexpectedly, this weakened dimerization elicits more sustained EGFR signaling than seen with EGF, provoking responses in breast cancer cells associated with differentiation rather than proliferation. Our results reveal how responses to different EGFR ligands are defined by receptor dimerization strength and signaling dynamics. These findings have broad implications for understanding receptor tyrosine kinase (RTK) signaling specificity. Our results also suggest parallels between partial and/or biased agonism in RTKs and G-protein-coupled receptors, as well as new therapeutic opportunities for correcting RTK signaling output. PMID- 28988775 TI - Outbreak of vaccine-preventable diseases in Muslim majority countries. AB - The increase in Muslim parents' refusal and hesitancy to accept childhood vaccination was identified as one of the contributing factors in the increase of vaccine-preventable diseases cases in countries such as Afghanistan, Malaysia and Pakistan. The spread of inaccurate and irresponsible information by the anti vaccination movement may inflict more harm than good on Muslim communities. To curb this issue, health authorities in Pakistan and Malaysia have resorted to imposing strict punishments on parents who refuse to allow their children to be vaccinated. Information addressing religious concerns such as the halal issue must be made priority and communicated well to the general public, encouraging not only the acceptance of vaccinations but motivating communities to play an active role in promoting vaccination. Local government of the affected region need to work towards creating awareness among Muslim parents that vaccinations are a preventative public health strategy that has been practised and acknowledged by many doctors of all faiths. PMID- 28988776 TI - Prevalence of influenza vaccine hesitancy at a tertiary care hospital in Riyadh, Saudi Arabia. AB - BACKGROUND: Influenza vaccine hesitancy is a major problem worldwide, with significant public health consequences. We aimed to determine the prevalence of influenza vaccine hesitancy and the effect of vaccine awareness campaigns on vaccine acceptance among three groups (parents, adult patients, and healthcare workers [HCWs]) at King Abdulaziz Medical City, a tertiary care hospital in Riyadh, Saudi Arabia. METHODS: The study was conducted during the 2015-2016 winter season. Participants anonymously completed a validated questionnaire on influenza vaccine hesitancy. RESULTS: Of the 300 study participants, 17% (n=51) expressed vaccine hesitancy. The most common reasons given for vaccine refusal were: "It doesn't have any positive effect or benefit" (n=11 [21%]), "I don't need it because I'm healthy" (n=9 [17%]), and "I think it causes serious side effects" (n=7 [13%]). The most common sources of information about the vaccine were awareness campaigns (98/267 [36%]) and medical staff (98/267 [36%]). One hundred and sixty-three [54%] respondents knew that the effect of the influenza vaccine lasts up to 1year. There was no significant relationship between education level and receiving influenza vaccination. The study showed that confidence towards the Saudi Ministry of Health and medical doctors among three groups of participants was very high; 97% of adults, 95% of parents, and 93% of HCWs expressed trusted information provided to them by the Ministry of Health, and 97% of adults, 99% of parents, and 90% of HCWs trusted their physicians' information. CONCLUSION: Influenza vaccine hesitancy was low at KAMC. The most common reason for vaccine refusal was believing that it had no positive effect and that it is unnecessary. The most common sources of information for influenza vaccine were awareness campaigns and medical staff. Participants had high levels of trust in both the Saudi Ministry of Health and doctors. PMID- 28988769 TI - Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer. AB - We report a comprehensive analysis of 412 muscle-invasive bladder cancers characterized by multiple TCGA analytical platforms. Fifty-eight genes were significantly mutated, and the overall mutational load was associated with APOBEC signature mutagenesis. Clustering by mutation signature identified a high mutation subset with 75% 5-year survival. mRNA expression clustering refined prior clustering analyses and identified a poor-survival "neuronal" subtype in which the majority of tumors lacked small cell or neuroendocrine histology. Clustering by mRNA, long non-coding RNA (lncRNA), and miRNA expression converged to identify subsets with differential epithelial-mesenchymal transition status, carcinoma in situ scores, histologic features, and survival. Our analyses identified 5 expression subtypes that may stratify response to different treatments. PMID- 28988777 TI - Delta-toxin from Clostridium perfringens perturbs intestinal epithelial barrier function in Caco-2 cell monolayers. AB - Clostridium perfringens delta-toxin is a beta-barrel-pore-forming toxin (beta PFT) and a presumptive virulence factor of type B and C strains, which are causative organisms of fatal intestinal diseases in animals. We showed previously that delta-toxin causes cytotoxicity via necrosis in sensitive cells. Here, we examined the effect of delta-toxin on intestinal membrane integrity. Delta-toxin led to a reduction in transepithelial electrical resistance (TEER) and increased the permeability of fluorescence isothiocyanate-conjugated dextran in human intestinal epithelial Caco-2 cells without changing the tight junction proteins, such as zonula occludens-1 (ZO-1), occludin, and claudin-1. On the other hand, delta-toxin reduced the cellular levels of adherence junction protein E-cadherin before cell injury. A disintegrin and metalloprotease (ADAM) 10 facilitates E cadherin cleavage and was identified as the cellular receptor for alpha-toxin, a beta-PFT produced by Staphylococcus aureus. ADAM10 inhibitor (GI254023X) blocked the toxin-induced decrease in TEER and cleavage of E-cadherin. Delta-toxin enhanced ADAM10 activity in a dose- and time-dependent manner. Furthermore, delta toxin colocalized with ADAM10. These results indicated that ADAM10 plays a key role in delta-toxin-induced intestinal injury. PMID- 28988780 TI - Clinical studies in restorative dentistry: Design, conduct, analysis. AB - OBJECTIVE: Clinical studies should be one main aspect underlying dentists' decision-making towards dental materials. Study design, conduct, analysis and reporting impact on the usefulness of studies. We discuss problems with current studies and highlight areas where improvement might be possible. METHODS: Based on systematically and non-systematically collected data, we demonstrate where and why current studies in clinical dentistry deliver less-than-optimal results. Lending from general medicine, we suggest ways forward for clinical dental material science. RESULTS: Randomized controlled (efficacy) trials remain a major pillar in dental material science, as they reduce selection bias and, if well designed and conducted, have high internal validity. Given their costs and limited external validity, alternatives like practice-based or pragmatic controlled trials or observational studies can complement the evidence-base. Prior to conduct, researchers should focus on study comparators and setting (answering questions with relevance to clinical dentistry), and pay attention to statistical power, considering the study aim (superiority or non-inferiority trial), the expected event rate, and attrition. Study outcomes should be chosen on the basis of a core outcome set or, if not available, involving patients and other stakeholders. Studies should be registered a priori, and reporting should adhere to standards. Possible clustering should be accounted for during statistical analysis. SIGNIFICANCE: Many clinical studies in dental material science are underpowered, and of limited validity and usefulness for daily decision-making. Dental researchers should mirror existing efforts in other medical fields in making clinical studies more valid and applicable, thus contributing to better dental care. PMID- 28988779 TI - Conceptual precision is key in acute stress research: A commentary on Shields, Sazma, & Yonelinas, 2016. AB - A recent meta-analytic review by Shields, Sazma, & Yonelinas (2016) brings to the fore several conceptual issues within the stress and executive function (EF) literatures. We present a critique of these issues, using the review as an exemplar of how stress and EF are often examined empirically. The review summarizes research suggesting that EF is not only trait-like, but can be also state-like, influenced by factors such as acute stress. It has numerous strengths including its scope in examining EF across domains, inclusion of moderators, and timeliness, given the rapidly expanding field of stress research. We argue that the conclusions would be less equivocal with a more precise and neurally-informed consideration of EF, stressor, and timing assessments. A detailed discussion of these issues is provided, using the inhibition EF domain as an example, in order to illustrate key limitations and potential consequences of broad inclusion criteria. We endeavor to promote precise, shared definitions in the service of delineating a more complete and consistent account of acute stress effects on EF. PMID- 28988778 TI - NMR structure and localization of a large fragment of the SARS-CoV fusion protein: Implications in viral cell fusion. AB - The lethal Coronaviruses (CoVs), Severe Acute Respiratory Syndrome-associated Coronavirus (SARS-CoV) and most recently Middle East Respiratory Syndrome Coronavirus, (MERS-CoV) are serious human health hazard. A successful viral infection requires fusion between virus and host cells carried out by the surface spike glycoprotein or S protein of CoV. Current models propose that the S2 subunit of S protein assembled into a hexameric helical bundle exposing hydrophobic fusogenic peptides or fusion peptides (FPs) for membrane insertion. The N-terminus of S2 subunit of SARS-CoV reported to be active in cell fusion whereby FPs have been identified. Atomic-resolution structure of FPs derived either in model membranes or in membrane mimic environment would glean insights toward viral cell fusion mechanism. Here, we have solved 3D structure, dynamics and micelle localization of a 64-residue long fusion peptide or LFP in DPC detergent micelles by NMR methods. Micelle bound structure of LFP is elucidated by the presence of discretely folded helical and intervening loops. The C terminus region, residues F42-Y62, displays a long hydrophobic helix, whereas the N-terminus is defined by a short amphipathic helix, residues R4-Q12. The intervening residues of LFP assume stretches of loops and helical turns. The N terminal helix is sustained by close aromatic and aliphatic sidechain packing interactions at the non-polar face. 15N{1H}NOE studies indicated dynamical motion, at ps-ns timescale, of the helices of LFP in DPC micelles. PRE NMR showed that insertion of several regions of LFP into DPC micelle core. Together, the current study provides insights toward fusion mechanism of SARS-CoV. PMID- 28988781 TI - Interleukin 4/13 receptors: An overview of genes, expression and functional role in teleost fish. AB - In superior vertebrates, Interleukin 4 (IL-4) and Interleukin 13 (IL-13) play key and diverse roles to support immune responses acting on cell surface receptors. When stimulated, receptors activate intracellular signalling cascades switching cell phenotypes according to stimuli. In teleost fish, Interleukin 4/13 (IL-4/13) is the ancestral family cytokine related to both IL-4 and IL-13. Every private and common receptor subunit for IL-4/13 have in fish at least two paralogues and, as in mammals, soluble forms are also part of the receptor system. Reports for findings of fish IL-4/13 receptors have covered comparative analysis, transcriptomic profiles and to a lesser extent, functional analysis regarding ligand-receptor interactions and their biological effects. This review addresses available information from fish IL-4/13 receptors and discusses overall implications on teleost immunity, summarized gene induction strategies and pathogen-induced gene modulation, which may be useful tools to enhance immune response. Additionally, we present novel coding sequences for Atlantic salmon (Salmo salar) common gamma chain receptor (gammaC), Interleukin 13 receptor alpha 1A chain (IL-13Ralpha1A) and Interleukin 13 receptor alpha 1B chain (IL 13Ralpha1B). PMID- 28988782 TI - Predictors of genitourinary malignancy in patients with asymptomatic microscopic hematuria. AB - OBJECTIVES: To report the incidence of genitourinary malignancy and identify associated risk factors in patients undergoing urologic evaluation for asymptomatic microscopic hematuria (AMH) according to the 2012 American Urologic Association guidelines. SUBJECTS/PATIENTS AND METHODS: A retrospective institutional review of patients who underwent evaluation for AMH between 2012 and 2015 was conducted. Covariates analyzed included age, sex, smoking status, history of other malignancy, history of pelvic irradiation, presence of irritative voiding symptoms, use of anticoagulation, number of red blood cells on microscopic urinalysis, and guideline adherence. Univariate analysis was performed to explore the association between these risk factors and the presence of genitourinary malignancy. RESULTS: Of the 1,049 patients analyzed with AMH, urologic malignancy was diagnosed in 12 patients (1.1%), including 1 upper-tract urothelial cancer, 5 renal tumors, and 6 bladder tumors. All patients with malignancy were over 50 years old. Older age, male sex, smoking history, and irritative voiding symptoms were associated with malignancy on univariate analysis. CONCLUSIONS: Our data adds to the growing evidence that the incidence of malignancy among patients with AMH is low. Risk factors associated with urinary tract cancer are male sex, age>50 years, smoking history, and irritative voiding symptoms. Further prospective, randomized trials would be useful for developing a more tailored screening protocol for low-risk patients. PMID- 28988783 TI - Adverse Pregnancy Outcomes in Asthmatic Women: A Population-Based Family Design Study. AB - BACKGROUND: Asthma is associated with several adverse pregnancy and perinatal outcomes. Familial factors may confound these associations. OBJECTIVE: To examine the role of measured and unmeasured confounding by conducting a study that compared differentially exposed cousins and siblings from the same families. METHODS: We retrieved data on adverse pregnancy outcomes, prescribed drugs, and physician-diagnosed asthma from nationwide registers for all women in Sweden with singleton births between 2001 and 2013. Logistic and linear regression estimated the association between maternal asthma and several outcomes in the whole population and within differently exposed pregnant relatives. RESULTS: In total, 1,075,153 eligible pregnancies were included and 10.1% of the study population had asthma. We identified 475,200 cousin and 341,205 sister pregnancies. Women with asthma had increased risks for preeclampsia (adjusted odds ratio [aOR], 1.17; 95% CI, 1.13-1.21), emergency cesarean section (aOR, 1.24; 95% CI, 1.22 1.27), and having a child small for gestational age (aOR, 1.18; 95% CI, 1.12 1.23). In the conditional regression analyses, after adjustment for familial factors, the associations remained: preeclampsia in cousins (aOR, 1.16; 95% CI, 1.07-1.25) and siblings (aOR, 1.23; 95% CI, 1.08-1.38), emergency cesarean section in cousins (aOR, 1.28) and siblings (aOR, 1.21), and small for gestational age in cousins (aOR, 1.17) and siblings (aOR, 1.13). CONCLUSIONS: Factors shared by siblings and cousins do not seem to explain the observed association between maternal asthma and adverse pregnancy outcomes. This implies that targeting the asthma disease will continue to be important in reducing risks for adverse outcomes in pregnancy. PMID- 28988785 TI - Chronic ocular complications of Stevens-Johnson syndrome associated with causative medications in Korea. PMID- 28988784 TI - Risk of Immediate-Type Allergy to Local Anesthetics Is Overestimated-Results from 5 Years of Provocation Testing in a Danish Allergy Clinic. AB - BACKGROUND: Local anesthetics (LAs) are used in many health care settings and exposure during a lifetime is almost inevitable. Immediate-type allergy to LAs is considered rare among allergy experts but is commonly suspected by health care workers from other specialties, and by patients. OBJECTIVE: The main aim of this study was to investigate the incidence of immediate-type allergy to LAs in our regional allergy clinic over the 5-year period 2010 to 2014. METHODS: This was a retrospective single-center study of patients referred to a regional allergy clinic (excluding patients with perioperative reactions) with suspected immediate allergy to LAs, who had undergone subcutaneous provocation with 1 or more LAs. Patients were identified in the hospital clinical coding system and clinical information about the reaction and investigation results was obtained from their medical records. RESULTS: A total of 164 patients (123 women/41 men; median age, 56 years; range, 7-89 years) who had 189 provocations with LAs were included over the 5-year period 2010 to 2014. All 164 patients had negative subcutaneous provocations to all 189 tests with LAs (95% CI, 0%-1.83%). Another allergen was identified in 10% (n = 17) of the patients. CONCLUSIONS: None of the 164 patients with suspected immediate-type allergy to LAs reacted on provocation. Thus, no patients have been diagnosed with an immediate allergy to LAs in our regional allergy clinic in the 5-year period studied, and allergy to LAs must be considered very rare. Alternative mechanisms should be considered, but if symptoms are consistent with allergy, other potential allergens should be investigated. PMID- 28988786 TI - Omalizumab for severe chronic spontaneous urticaria: Real-life experiences of 280 patients. PMID- 28988788 TI - A systematic review and meta-analysis on the treatment of liver hydatid cyst: Comparing laparoscopic and open surgeries. AB - BACKGROUND AND STUDY AIMS: There is an academic debate regarding surgical interventions for liver hydatid cyst disease. The purpose of the current systematic review and meta-analysis study was to analyse the pros and cons of open surgery and laparoscopic techniques, considering the outcomes of liver hydatid cysts. METHODS: Descriptive Boolean queries were used to search PubMed and Scopus for articles published between January 2000 and December 2016 to evaluate the outcomes of liver hydatid cyst in terms of mortality, post-operative complications, cure rate and recurrences. The data related to the four outcomes of liver hydatid cyst were extracted, assessed and then used as their corresponding effect sizes in the meta-analysis process. RESULTS: Six studies totally consisting of 1028 patients [open surgery group=816 (+7 converted to lap) and laparoscopic group=212] were analysed. In this meta-analysis study, random effects models of outcomes (i.e. post-operative complications, mortalities, recurrences and cure rate) of the two procedures were OR=0.852, LL=0.469, UL=1.546, Z=-0.526, p=0.599 (for post-operative complications); OR=0.849, LL=0.141, UL=5.105, Z=-0.179, p=0.858 (for mortality); OR=0.903, LL=0.166, UL=4.906, Z=-0.119, p=0.906 (for recurrence); and OR=0.459, LL=0.129, UL=1.637, Z=-1.201, p=0.230 (for cure rate). Meta-analysis and illustrated forest plots showed that there are no superiorities between the two approaches. The results of heterogeneity tests of the above mentioned outcomes were Q=8.083, df=5, p=0.152, I2=38.142% for post-operative complications; Q=0.127, df=2, p=0.938, I2=0% for mortality; Q=4.984, df=2, p=0.083, I2=59.874% for recurrence; and Q=10.639, df=5, p=0.059, I2=53.001% for cure rate. The results of regression tests based on Egger's, smoothed variance based on Egger (SVE) and smoothed variance based on Thomson (SVT) showed that the p values are not significant, and there are neither significant statistical differences nor publication bias between the outcomes of the two treatment procedures. CONCLUSION: The results show no promising trends towards advantages of open versus laparoscopic surgeries in the treatment of liver hydatid cyst. However, informative measurement values for comparing these surgeries could be derived for complications, recurrence, mortality and cure rates. Furthermore, all three tests, namely Egger's, SVE and SVT regression models, were used to assess publication bias and showed no evidence for the existence of publication bias. PMID- 28988787 TI - Fascioliasis: A report on a case presenting with abdominal pain. PMID- 28988789 TI - Highlights from Gastro Update Europe - Vienna April 6-8, 2017. PMID- 28988790 TI - Recent diagnostic procedures for colorectal cancer screening: Are they cost effective? AB - Colorectal cancer (CRC) is the third most common cancer worldwide and the fourth most common cause of death. Reduction in mortality rates in some countries worldwide are most likely ascribed to CRC screening and/or improved treatments. We reviewed the most relevant articles which discuss the cost-effectiveness of colorectal cancer screening procedures, in particular, the recent ones through the last eight years. The effectiveness of screening estimated by discounted life years gained (LYGs) compared to no screening, differed considerably between the studies. Despite these differences, all studies consistently emphasized that screening for CRC was cost-effective compared with no screening for each of the recognized screening strategies. Newer technologies for colorectal cancer screening, including computed tomographic colonography (CTC), faecal DNA test, and Pillcam Colon are less invasive and accurate, however, they are not cost effective, as their cost was higher than all other established screening strategies. When compliance and adherence to such new techniques are increased more than the established strategies they would be more cost-effective particularly CTC. PMID- 28988791 TI - Treating cholera in severely malnourished children in the Horn of Africa and Yemen. PMID- 28988792 TI - Department of Error. PMID- 28988793 TI - The Combined Roles of Nonsomatic Depressive Symptomatology, Neurocognitive Function, and Current Substance Use in Medication Adherence in Adults Living With HIV Infection. AB - Depression, global neurocognitive (GNC) function, and substance use disorders (SUDs) are each associated with medication adherence in persons living with HIV (PLWH). Because somatic symptoms can inflate depression scores in PLWH, the role of nonsomatic depressive symptomatology (NSDS) should be considered in adherence. However, the combined roles of NSDS, GNC function, and current SUDs in predicting combined antiretroviral therapy (cART) adherence remain poorly understood. Forty PLWH (70% Latina/o; 30% non-Hispanic White) completed psychiatric/SUD, neurocognitive, and self-report cART adherence evaluations. Higher NSDS was associated with suboptimal adherence (p < .01), but optimal and suboptimal adherers did not differ in GNC function or current SUDs. Only NSDS was associated with suboptimal adherence, after accounting for GNC function and SUDs (p = .01). NSDS uniquely predicted self-reported adherence, beyond GNC function and current SUDs among ethnically diverse PLWH. Methodological issues between present and prior studies should also be considered. PMID- 28988794 TI - Towards a Contrast free Approach at EVAR: a New Look at an Old Tool - CO2 Angiography. PMID- 28988795 TI - Exposure to elemental composition of outdoor PM2.5 at birth and cognitive and psychomotor function in childhood in four European birth cohorts. AB - BACKGROUND: Little is known about developmental neurotoxicity of particulate matter composition. We aimed to investigate associations between exposure to elemental composition of outdoor PM2.5 at birth and cognitive and psychomotor functions in childhood. METHODS: We analyzed data from 4 European population based birth cohorts in the Netherlands, Germany, Italy and Spain, with recruitment in 2000-2006. Elemental composition of PM2.5 measurements were performed in each region in 2008-2011 and land use regression models were used to predict concentrations at participants' residential addresses at birth. We selected 8 elements (copper, iron, potassium, nickel, sulfur, silicon, vanadium and zinc) and used principal component analysis to combine elements from the same sources. Cognitive (general, verbal, and non-verbal) and psychomotor (fine and gross) functions were assessed between 1 and 9years of age. Adjusted cohort specific effect estimates were combined using random-effects meta-analysis. RESULTS: 7246 children were included in this analysis. Single element analysis resulted in negative association between estimated airborne iron and fine motor function (-1.25 points [95% CI -2.45 to -0.06] per 100ng/m3 increase of iron). Association between the motorized traffic component, derived from principal component analysis, and fine motor function was not significant (-0.29 points [95% CI -0.64 to 0.06] per unit increase). None of the elements were associated with gross motor function or cognitive function, although the latter estimates were predominantly negative. CONCLUSION: Our results suggest that iron, a highly prevalent element in motorized traffic pollution, may be a neurotoxic compound. This raises concern given the ubiquity of motorized traffic air pollution. PMID- 28988797 TI - Altered expression of interferon-stimulated genes is strongly associated with therapeutic outcomes in hepatitis B virus infection. AB - Our previous OSST study shows that switching to pegylated interferon (Peg-IFN) alpha2a results in higher rates of response hepatitis B e antigen (HBeAg) seroconversion and hepatitis B surface antigen (HBsAg) loss at the end of treatment, compared with nucleot(s)ide analogues (NAs) monotherapy in long term NA-treated chronic hepatitis B (CHB) patients. In order to characterize the correlation between Peg-IFN-alpha antiviral effect and IFN-inducing signaling in CHB patients who switched to Peg-IFN from long time entecavir (ETV) treatment, we investigated the dynamic expression of interferon-stimulated genes (ISGs), including STAT1, MX, and a negative regulatory factor, suppressor of cytokine signaling 3(SOCS3), which negatively regulate IFN JAK-STAT signaling pathway by interacting with STAT1 and STAT2, in peripheral blood and paired liver samples, obtained from 54 CHB patients enrolled in a clinical trial, OSST study. In Peg IFN group, responders showed a more significant decline in HBsAg, compared with non-responders. Following the treatment, peripheral blood and hepatic STAT1 and MX expression levels were higher in Peg-IFN responders, while SOCS3 expression was higher in non-responders. Fold induction of STAT1 at week 4 and MX at week 12 in PBMCs directly correlated with HBsAg decline at week 48 relative to the baseline. Responders showed a significantly increased activation and nuclear localization of phospho-STAT1 following Peg-IFN treatment, compared with non responders in liver. Whereas, non-responders exhibited significantly higher hepatic expression of SOCS3 before the treatment compared with the responders and even higher expression levels after the treatment compared with the baseline, which may be involved in the mechanism of IFN resistance. PMID- 28988796 TI - Nitrogen dioxide exposure in school classrooms of inner-city children with asthma. AB - BACKGROUND: Ambient and home exposure to nitrogen dioxide (NO2) causes asthma symptoms and decreased lung function in children with asthma. Little is known about the health effects of school classroom pollution exposure. OBJECTIVE: We aimed to determine the effect of indoor classroom NO2 on lung function and symptoms in inner-city school children with asthma. METHODS: Children enrolled in the School Inner-City Asthma Study were followed for 1 academic year. Subjects performed spirometry and had fraction of exhaled nitric oxide values measured twice during the school year at school. Classroom NO2 was collected by means of passive sampling for 1-week periods twice per year, coinciding with lung function testing. Generalized estimating equation models assessed lung function and symptom relationships with the temporally nearest classroom NO2 level. RESULTS: The mean NO2 value was 11.1 ppb (range, 4.3-29.7 ppb). In total, exposure data were available for 296 subjects, 188 of whom had complete spirometric data. At greater than a threshold of 8 ppb of NO2 and after adjusting for race and season (spirometry standardized by age, height, and sex), NO2 levels were associated highly with airflow obstruction, such that each 10-ppb increase in NO2 level was associated with a 5% decrease in FEV1/forced vital capacity ratio (beta = -0.05; 95% CI, -0.08 to -0.02; P = .01). Percent predicted forced expiratory flow between the 25th and 75th percentile of forced vital capacity was also inversely associated with higher NO2 exposure (beta = -22.8; 95% CI, -36.0 to -9.7; P = .01). There was no significant association of NO2 levels with percent predicted FEV1, fraction of exhaled nitric oxide, or asthma symptoms. Additionally, there was no effect modification of atopy on lung function or symptom outcomes. CONCLUSION: In children with asthma, indoor classroom NO2 levels can be associated with increased airflow obstruction. PMID- 28988800 TI - The Effects of Stochasticity at the Single-Cell Level and Cell Size Control on the Population Growth. AB - Establishing a quantitative connection between the population growth rate and the generation times of single cells is a prerequisite for understanding evolutionary dynamics of microbes. However, existing theories fail to account for the experimentally observed correlations between mother-daughter generation times that are unavoidable when cell size is controlled for, which is essentially always the case. Here, we study population-level growth in the presence of cell size control and corroborate our theory using experimental measurements of single cell growth rates. We derive a closed formula for the population growth rate and demonstrate that it only depends on the single-cell growth rate variability, not other sources of stochasticity. Our work provides an evolutionary rationale for the narrow growth rate distributions often observed in nature: when single-cell growth rates are less variable but have a fixed mean, the population will exhibit an enhanced population growth rate as long as the correlations between the mother and daughter cells' growth rates are not too strong. PMID- 28988798 TI - Differential carbonylation of proteins in end-stage human fatty and nonfatty NASH. AB - OBJECTIVE: In the liver, a contributing factor in the pathogenesis of non alcoholic fatty liver disease is oxidative stress leading to the accumulation of highly reactive electrophilic alpha/beta unsaturated aldehydes. The objective of this study was to determine if significant differences were evident when evaluating carbonylation in human end-stage fatty nonalcoholic steatohepatitis (fNASH) compared to end-stage nonfatty NASH (nfNASH). METHODS: Using hepatic tissue obtained from healthy humans and patients diagnosed with end stage nfNASH or fNASH, overall carbonylation was assessed by immunohistochemistry (IHC) and LC MS/MS followed by bioinformatics. RESULTS: Picrosirius red staining revealed extensive fibrosis in both fNASH and nfNASH which corresponded with increased reactive aldehyde staining. Although significantly elevated when compared to normal hepatic tissue, no significant differences in overall carbonylation and fibrosis were evident when comparing fNASH with nfNASH. Examining proteins that are critical for anti-oxidant defense revealed elevated expression of thioredoxin, thioredoxin interacting protein, glutathione S-transferase p1 and mitochondrial superoxide dismutase in human NASH. As important, using immunohistochemistry, significant colocalization of the aforementioned proteins occurred in cytokeratin 7 positive cells indicating that they are part of the ductular reaction. Expression of catalase and Hsp70 decreased in both groups when compared to normal human liver. Mass spectrometric analysis revealed a total of 778 carbonylated proteins. Of these, 194 were common to all groups, 124 unique to tissue prepared from healthy individuals, 357 proteins exclusive to NASH, 124 proteins distinct to samples from patients with fNASH and 178 unique to nfNASH. Using functional enrichment analysis of hepatic carbonylated proteins revealed a propensity for increased carbonylation of proteins regulating cholesterol and Huntington's disease related pathways occurred in nfNASH. Examining fNASH, increased carbonylation was evident in proteins regulating Rho cytoskeletal pathways, nicotinic acetylcholine receptor signaling and chemokine/cytokine inflammatory pathways. Using LC-MS/MS analysis and trypsin digests, sites of carbonylation were identified on peptides isolated from vimentin, endoplasmin and serum albumin in nfNASH and fNASH respectively. CONCLUSIONS: These results indicate that cellular factors regulating mechanisms of protein carbonylation may be different depending on pathological diagnosis of NASH. Furthermore these studies are the first to use LC-MS/MS analysis of carbonylated proteins in human NAFLD and explore possible mechanistic links with end stage cirrhosis due to fatty liver disease and the generation of reactive aldehydes. PMID- 28988801 TI - A Padawan Programmer's Guide to Developing Software Libraries. AB - With the rapid adoption of computational tools in the life sciences, scientists are taking on the challenge of developing their own software libraries and releasing them for public use. This trend is being accelerated by popular technologies and platforms, such as GitHub, Jupyter, R/Shiny, that make it easier to develop scientific software and by open-source licenses that make it easier to release software. But how do you build a software library that people will use? And what characteristics do the best libraries have that make them enduringly popular? Here, we provide a reference guide, based on our own experiences, for developing software libraries along with real-world examples to help provide context for scientists who are learning about these concepts for the first time. While we can only scratch the surface of these topics, we hope that this article will act as a guide for scientists who want to write great software that is built to last. PMID- 28988803 TI - Effects of the bioactive peptides Ile-Pro-Pro and Val-Pro-Pro upon autonomic neurotransmission and blood pressure in spontaneously hypertensive rats. AB - The bioactive peptides Ile-Pro-Pro (IPP) and Val-Pro-Pro (VPP) are believed to improve blood pressure and arterial function. To gain a better understanding of the mechanisms underlying the action of these peptides, we investigated their effects upon autonomic neurotransmission and blood pressure in spontaneously hypertensive rats (SHR). Both IPP and VPP caused a significant reduction in cutaneous arterial sympathetic nerve activity (CASNA) and reduced mean arterial pressure (MAP); however, both of these effects were eliminated following sub diaphragmatic vagotomy. On the other hand, captopril, an angiotensin-converting enzyme inhibitor, reduced MAP without changing CASNA, and maintained this hypotensive effect following vagotomy. Moreover, the effects of IPP and VPP upon CASNA were observed following gastric administration but not by duodenal administration. These results suggest that IPP and VPP reduce CASNA via the stomach and afferent vagus nerve, thus causing reductions in MAP in SHR. PMID- 28988799 TI - Dysfunction of autophagy and endosomal-lysosomal pathways: Roles in pathogenesis of Down syndrome and Alzheimer's Disease. AB - Individuals with Down syndrome (DS) have an increased risk of early-onset Alzheimer's Disease (AD), largely owing to a triplication of the APP gene, located on chromosome 21. In DS and AD, defects in endocytosis and lysosomal function appear at the earliest stages of disease development and progress to widespread failure of intraneuronal waste clearance, neuritic dystrophy and neuronal cell death. The same genetic factors that cause or increase AD risk are also direct causes of endosomal-lysosomal dysfunction, underscoring the essential partnership between this dysfunction and APP metabolites in AD pathogenesis. The appearance of APP-dependent endosome anomalies in DS beginning in infancy and evolving into the full range of AD-related endosomal-lysosomal deficits provides a unique opportunity to characterize the earliest pathobiology of AD preceding the classical neuropathological hallmarks. Facilitating this characterization is the authentic recapitulation of this endosomal pathobiology in peripheral cells from people with DS and in trisomy mouse models. Here, we review current research on endocytic-lysosomal dysfunction in DS and AD, the emerging importance of APP/betaCTF in initiating this dysfunction, and the potential roles of additional trisomy 21 genes in accelerating endosomal-lysosomal impairment in DS. Collectively, these studies underscore the growing value of investigating DS to probe the biological origins of AD as well as to understand and ameliorate the developmental disability of DS. PMID- 28988805 TI - Prediction of massive blood transfusion in battlefield trauma: Development and validation of the Military Acute Severe Haemorrhage (MASH) score. AB - BACKGROUND: The predominant cause of preventable trauma death is bleeding, and many of these patients need resuscitation with massive blood transfusion. In resource-constrained environments, early recognition of such patients can improve planning and reduce wastage of blood products. No existing decision rule is sufficiently reliable to predict those patients requiring massive blood transfusion. This study aims to produce a decision rule for use on arrival at hospital for patients sustaining battlefield trauma. METHODS: A retrospective database analysis was undertaken using the UK Joint Theatre Trauma Registry to provide a derivation and validation dataset. Regression analysis of potential predictive factors was performed. Predictive factors were analysed through multi logistic regression analysis to build predictive models; sensitivity and specificity of these models was assessed, and the best fit models were analysed in the validation dataset. RESULTS: A decision rule was produced using a combination of injury pattern, clinical observations and pre-hospital data. The proposed rule, using a score of 3 or greater, demonstrated a sensitivity of 82.7% and a specificity of 88.8% for prediction of massive blood transfusion, with an AUROC of 0.93 (95% CI 0.91-0.95). CONCLUSIONS: We have produced a decision tool with improved accuracy compared to any previously described tools that can be used to predict blood transfusion requirements in the military deployed hospital environment. PMID- 28988804 TI - The experience and understanding of pain management in recently discharged adult trauma patients: A qualitative study. AB - INTRODUCTION: Pain following injury is often intense, prolonged and debilitating. If poorly managed, this acute pain has the potential to delay rehabilitation and lead to chronic pain. Recent quantitative Australian research recommends implementing further information and interventions to improve trauma patient outcomes, however, to ensure effectiveness, exploration of the patient perspective is imperative to ensure the success of future pain management strategies. This study aimed to gain understanding about the experience of pain management using prescribed analgesic regimens of recently discharged adult trauma patients. METHOD: Semi-structured interviews were used to explore the experiences and understandings of trauma patients in managing pain using prescribed analgesic regimens during the initial post-hospital discharge period. Twelve participants were purposively selected over a 6-month period at a level one trauma outpatient clinic based on questionnaire responses indicating pain related concerns. Qualitative data were thematically analysed. RESULTS: The overarching finding was that injuries and inadequate pain management incapacitate the patient at home. Four main themes were developed: injury pain is unique and debilitating; patients are uninformed at hospital discharge; patients have low confidence with pain management at home; and patients make independent decisions about pain management. Patients felt they were not given adequate information at hospital discharge to support them to make effective decisions about their pain management practices at home. CONCLUSION: There is a need for more inclusive and improved hospital discharge processes that includes patient and family education around pain management following injury. To achieve this, clinician education, support and training is essential. PMID- 28988806 TI - 3D assessment of damaged bicycle helmets and corresponding craniomaxillo mandibular skull injuries: A feasibility study. AB - OBJECTIVES: In the Netherlands, cyclists continue to outnumber other road users in injuries and deaths. The wearing of bicycle helmets is not mandatory in the Netherlands even though research has shown that wearing bicycle helmets can reduce head and brain injuries by up to 88%. Therefore, the aim of this study was to assess the feasibility of using 3D technology to evaluate bicycle-related head injuries and helmet protection. METHODS: Three patients who had been involved in a bicycle accident while wearing a helmet were subjected to multi-detector row computed tomography (MDCT) imaging after trauma. The helmets were separately scanned using the same MDCT scanner with tube voltages ranging from 80kVp to 140kVp and tube currents ranging from 10mAs to 300mAs in order to determine the best image acquisition parameters for helmets. The acquired helmet images were converted into virtual 3D surface hence Standard Tessellation Language (STL) models and merged with MDCT-derived STL models of the patients' skulls. Finally, all skull fractures and corresponding helmet damage were visualized and related. RESULTS: Imaging bicycle helmets on an MDCT scanner proved to be feasible using a tube voltage of 120kVp and a tube current of 120mAs. Merging the resulting STL models of the patients' skull and helmet allowed the overall damage sustained by both skull and helmet to be related. CONCLUSION: Our proposed 3D method of assessing bicycle helmet damage and corresponding head injuries could offer valuable information for the development and design of safer bicycle helmets. PMID- 28988807 TI - Increased risk for complications following removal of hardware in patients with liver disease, pilon or pelvic fractures: A regression analysis. AB - PURPOSE: Indications for removing orthopedic hardware on an elective basis varies widely. Although viewed as a relatively benign procedure, there is a lack of data regarding overall complication rates after fracture fixation. The purpose of this study is to determine the overall short-term complication rate for elective removal of orthopedic hardware after fracture fixation and to identify associated risk factors. MATERIALS AND METHODS: Adult patients indicated for elective hardware removal after fracture fixation between July 2012 and July 2016 were screened for inclusion. Inclusion criteria included patients with hardware related pain and/or impaired cosmesis with complete medical and radiographic records and at least 3-month follow-up. Exclusion criteria were those patients indicated for hardware removal for a diagnosis of malunion, non-union, and/or infection. Data collected included patient age, gender, anatomic location of hardware removed, body mass index, ASA score, and comorbidities. Overall complications, as well as complications requiring revision surgery were recorded. Statistical analysis was performed with SPSS 20.0, and included univariate and multivariate regression analysis. RESULTS: 391 patients (418 procedures) were included for analysis. Overall complication rates were 8.4%, with a 3.6% revision surgery rate. Univariate regression analysis revealed that patients who had liver disease were at significant risk for complication (p=0.001) and revision surgery (p=0.036). Multivariate regression analysis showed that: 1) patients who had liver disease were at significant risk of overall complication (p=0.001) and revision surgery (p=0.039); 2) Removal of hardware following fixation for a pilon had significantly increased risk for complication (p=0.012), but not revision surgery (p=0.43); and 3) Removal of hardware for pelvic fixation had a significantly increased risk for revision surgery (p=0.017). CONCLUSIONS: Removal of hardware following fracture fixation is not a risk-free procedure. Patients with liver disease are at increased risk for complications, including increased risk for needing revision surgery following hardware removal. Patients having hardware removed following fixation for pilon fractures also are at increased risk for complication, although they may not require a return trip to the operating room. Finally, removal of pelvic hardware is associated with a higher return to the operating room. PMID- 28988802 TI - A Community Challenge for Inferring Genetic Predictors of Gene Essentialities through Analysis of a Functional Screen of Cancer Cell Lines. AB - We report the results of a DREAM challenge designed to predict relative genetic essentialities based on a novel dataset testing 98,000 shRNAs against 149 molecularly characterized cancer cell lines. We analyzed the results of over 3,000 submissions over a period of 4 months. We found that algorithms combining essentiality data across multiple genes demonstrated increased accuracy; gene expression was the most informative molecular data type; the identity of the gene being predicted was far more important than the modeling strategy; well-predicted genes and selected molecular features showed enrichment in functional categories; and frequently selected expression features correlated with survival in primary tumors. This study establishes benchmarks for gene essentiality prediction, presents a community resource for future comparison with this benchmark, and provides insights into factors influencing the ability to predict gene essentiality from functional genetic screens. This study also demonstrates the value of releasing pre-publication data publicly to engage the community in an open research collaboration. PMID- 28988808 TI - Impact of new International Association of Diabetes and Pregnancy Study Groups (IADPSG) diagnostic criteria on perinatal outcomes in a regional tertiary hospital in New South Wales, Australia. AB - AIMS: We compared the impact of new gestational diabetes (GDM) diagnostic criteria by IADPSG with previous criteria to ascertain concordance between the two criteria; and whether women discordant for GDM between the old and new criteria had increased pregnancy complications. METHODS: Oral glucose tolerance tests of pregnant women across time periods using old criteria and new criteria were collected. Maternal data and perinatal outcomes were compared between diagnostic concordant and discordant women. RESULTS: In total, 666/5178 (12.9%) women were diagnosed and treated for GDM. There was a significant increase in odds of any complication in concordant positive women (OR 3.91 95%CI 2.71-5.63, p<.0001); in women only positive by new GDM criteria (OR 2.06, 95% CI 1.41-2.99, p=.0002); and women only positive by old GDM criteria (OR 2.28, 95% CI 1.42-3.66, p=.0006); compared to concordant negative women. This is mainly due to macrosomia and nursery admissions. CONCLUSION: This study confirms that women diagnosed with GDM on both old and new criteria have a higher rate of birth complications than women without GDM. Women who have been missed out due to new criteria may still be at risk. Therefore, combination of both old and new criteria may be optimal for identifying high-risk pregnancies. PMID- 28988809 TI - Commentary on "Primary female epispadias: Perineal approach or Kelly repair?" PMID- 28988810 TI - RE: Winship BB, Rushton HG, Pohl HG. In pursuit of the perfect penis: Hypospadias repair outcomes. J Pediatr Urol 2017; 13: 285-8. PMID- 28988811 TI - Featuring: Spinal anesthesia for pediatric urological surgery: Reducing the theoretic neurotoxic effects of general anesthesia. PMID- 28988813 TI - Asthma Management for the Otolaryngologist. AB - Asthma is a chronic inflammatory disease that will frequently be encountered by otolaryngologists as they manage their patients with upper respiratory diseases. Symptoms such as cough should alert otolaryngologists to consider more broadly the potential role of asthma in the differential diagnosis. It is critical for otolaryngologists to appreciate that patients with allergic rhinitis and chronic rhinosinusitis will often have asthma, and that many of them may not be diagnosed at the time of presentation. Appropriate diagnosis of the patient with asthma, as well as effective treatment for its symptoms, will improve patient function and enhance quality of life. PMID- 28988812 TI - High throughput sequencing-based analysis of microbial diversity in dental unit waterlines supports the importance of providing safe water for clinical use. AB - This study aims to explore the water quality of dental unit waterlines (DUWLs) and the diversity of microbial communities in DUWLs. Water samples from 33 dental chair units (DCUs) were collected, diluted and then spread on sterilized R2A plate for incubation. Subsequently, the microbial colony-forming units per milliliter (CFU/ml) were recorded by an automatic colony analyzer. Total DNA extracted from the rest of the samples was tested on the Illumina MiSeq PE300 platform. T-test and Kruskal-Wallis rank test were adopted for statistical analysis. Significance was assumed at a P<0.05. After incubation, the average total microbial count was 21,413.13+/-17,861.00CFU/ml. High-throughput sequencing revealed 10 bacterial phyla, including 9 identified and 1 unclassified phyla. Totally 63 sequences were identified at the genus level, including 42 genera, 3 tentative species and 18 unclassified genera. In addition, 7 potential human pathogenic bacteria were detected. In summary, department, brand and service life of DCUs do not influence the water quality of DUWLs significantly. The diversity of microbial communities in DUWLs is abundant and includes both pathogenic and some unknown bacteria. PMID- 28988814 TI - The Role of the Sinonasal Epithelium in Allergic Rhinitis. AB - The sinonasal epithelial barrier is comprised of tight and adherens junction proteins. Disruption of epithelial barrier function has been hypothesized to contribute to allergic disease such as allergic rhinitis through increased passage of antigens and exposure of underlying tissue to these stimuli. Several mechanisms of sinonasal epithelial barrier disruption include antigen proteolytic activity, inflammatory cytokine-mediated tight junction breakdown, or exacerbation from environmental stimuli. Mechanisms of sinonasal epithelial barrier stabilization include corticosteroids and nuclear erythroid 2-related factor 2 (Nrf2) cytoprotective pathway activation. Additional studies will aid in determining the contribution of epithelial barrier function in allergic rhinitis pathophysiology and treatment. PMID- 28988815 TI - Advancements and Dilemmas in the Management of Allergy. AB - Recent advances in the diagnosis and management of allergic disease also lead to new clinical decisions for providers. Advances in component (or molecular) diagnostic testing for allergy continue to build in the literature, but diagnosing inhalant allergy remains largely unchanged clinically. Prevention of allergy has been demonstrated by preventing peanut allergy in high-risk infants by intentional oral exposure to promote tolerance. Immunotherapy options have increased, with literature supporting sublingual drops, sublingual tablets, and subcutaneous immunotherapy. Expanded options create clinical questions such as the role of monotherapy in polysensitized patients. This article explores recent advances and their clinical implications. PMID- 28988816 TI - Effectiveness of cognitive-behavioural therapy for post-disaster distress in post traumatic stress symptoms after Chilean earthquake and tsunami. AB - OBJECTIVE: This is the first time that the effectiveness of cognitive-behavioural therapy for post-disaster stress (CBT-PD) in symptoms of posttraumatic stress disorder (PTSD) has been tested outside the United States of America. DESIGN: Quasi-experiment with three groups. In the quasi-control group, complete CBT-PD was applied even though its members did not have PTSD; in quasi-experimental conditions, participants received complete treatment because they had this diagnosis; and in the third group, participants with PTSD received an abbreviated treatment (double sessions) due to organisational requirements. LOCATION: Primary health care workers in Constitucion (Chile), city exposed to earthquake and tsunami; public department workers in Talca (city exposed only to earthquake) and teachers from a school (Constitucion). PARTICIPANTS: A total of 13 of the 91 people diagnosed with PTSD participated. In addition, 16 people without diagnosis voluntarily participated. The treatment was completed by 29 participants. There were no dropouts. Only 1 of the 9 participants in the quasi-experimental group did not respond to treatment. INTERVENTIONS: CBT-PD is a group therapy (10-12 sessions) that includes psychoeducation, breathing retraining, behavioural activation and cognitive restructuring. CBT-PD (complete and abbreviated) was applied between September and December 2010. MEASUREMENTS: Short Posttraumatic Stress Disorder Rating Interview (SPRINT-E) was used to measure PTSD symptoms before and after treatment. RESULTS: The group that received the complete treatment and was diagnosed with PTSD showed a significant decrease in the total symptoms to below dangerous levels (IGAAB: 31.556; p<0.01; 95%CI: 0.21-2.01]; eta2=0.709). DISCUSSION: The effectiveness and benefits of incorporating CBT-PD in the health network after events like disasters were discussed. PMID- 28988817 TI - A Systematic Review and Meta-Analysis of the Efficacy of Manipulative Therapy in Women with Primary Dysmenorrhea. AB - OBJECTIVE: To assess the robustness of evidence for the efficacy of manipulative therapy in women with primary dysmenorrhea. METHOD: Seven electronic databases were searched for studies reporting data on manipulative therapy for women with primary dysmenorrhea. The primary and secondary outcomes were pain relief and quality of life, respectively. Quality of eligible studies was assessed using the Physiotherapy Evidence Database (PEDro) guideline. RESULTS: The search yielded 19 citations of which four were systematically reviewed and three eligible for meta analysis. The systematic review showed above moderate methodological quality with a mean of 6.7 out of 10 on the PEDro quality scale. Manipulative therapy showed evidence of pain reduction in primary dysmenorrhea. CONCLUSION: Manipulative therapy could be considered as adjunct therapy in the relief of pain in primary dysmenorrhea. More high-quality research is needed before the evidence for their utilization can be ascertained. Particularly, items related to assessor blinding should be considered in future studies. PMID- 28988818 TI - Assessing outcome following levatorplasty: When East meets West: Editorial on paper "Transcutaneous aponeurotic repair with small detachment of the levator aponeurosis for aponeurotic blepharoptosis in Japanese patients". PMID- 28988819 TI - An in vitro cytotoxic approach to assess the toxicity of heavy metals and their binary mixtures on hippocampal HT-22 cell line. AB - Humans are exposed to a cocktail of heavy metal toxicants in the environment. Though heavy metals are deleterious, there is a paucity of information on the toxicity of mixtures. In this study, four common neurotoxicity heavy metals lead (Pb) cadmium (Cd), arsenic (As), and methylmercury (MeHg) were exposed individually and as mixtures to HT-22 cell line for 8days. The study established that low dose exposures induced toxicity to the HT-22 cell line during 8days. The results indicates potency dependent response, the toxicity of single metals on the HT-22 cells; MeHg > As > Cd > Pb. The cytotoxicity data of single metals were used to determine the mixtures interaction profile by using the dose additivity and effect additivity method. Metal mixtures showed higher toxicities compared to individual metals. Synergistic, antagonistic or additive effects of the toxicity were observed in different mixtures in low dose exposure. The interactive responses of mixtures depend on the co-exposure metal and their respective concentration. We concluded that the combined effects should be considered in the risk assessment of heavy metal co-exposure and potency. In future, comprehensive mechanistic based investigations needed for understanding the real interactive mixtures effects at molecular level. PMID- 28988821 TI - Cold-Induced Thermogenesis Depends on ATGL-Mediated Lipolysis in Cardiac Muscle, but Not Brown Adipose Tissue. AB - Fatty acids (FAs) activate and fuel UCP1-mediated non-shivering thermogenesis (NST) in brown adipose tissue (BAT). Release of FAs from intracellular fat stores by adipose triglyceride lipase (ATGL) is considered a key step in NST. Accordingly, the severe cold intolerance of global ATGL knockout (AKO) mice has been attributed to defective BAT lipolysis. Here we show that this conclusion is incorrect. We demonstrate that although the BAT-specific loss of ATGL impairs BAT lipolysis and alters BAT morphology, it does not compromise the beta3-adrenergic thermogenic response or cold-induced NST. Instead, NST depends on nutrient supply or lipolysis in white adipose tissue during fasting, suggesting that circulating energy substrates are sufficient to fuel NST. Cold intolerance in AKO mice is not caused by BAT dysfunction as previously suspected but by severe cardiomyopathy. We conclude that functional NST requires adequate substrate supply and cardiac function, but does not depend on ATGL-mediated lipolysis in BAT. PMID- 28988820 TI - ATF4-Induced Metabolic Reprograming Is a Synthetic Vulnerability of the p62 Deficient Tumor Stroma. AB - Tumors undergo nutrient stress and need to reprogram their metabolism to survive. The stroma may play a critical role in this process by providing nutrients to support the epithelial compartment of the tumor. Here we show that p62 deficiency in stromal fibroblasts promotes resistance to glutamine deprivation by the direct control of ATF4 stability through its p62-mediated polyubiquitination. ATF4 upregulation by p62 deficiency in the stroma activates glucose carbon flux through a pyruvate carboxylase-asparagine synthase cascade that results in asparagine generation as a source of nitrogen for stroma and tumor epithelial proliferation. Thus, p62 directly targets nuclear transcription factors to control metabolic reprogramming in the microenvironment and repress tumorigenesis, and identifies ATF4 as a synthetic vulnerability in p62-deficient tumor stroma. PMID- 28988822 TI - Lipolysis in Brown Adipocytes Is Not Essential for Cold-Induced Thermogenesis in Mice. AB - Lipid droplet (LD) lipolysis in brown adipose tissue (BAT) is generally considered to be required for cold-induced nonshivering thermogenesis. Here, we show that mice lacking BAT Comparative Gene Identification-58 (CGI-58), a lipolytic activator essential for the stimulated LD lipolysis, have normal thermogenic capacity and are not cold sensitive. Relative to littermate controls, these animals had higher body temperatures when they were provided food during cold exposure. The increase in body temperature in the fed, cold-exposed knockout mice was associated with increased energy expenditure and with increased sympathetic innervation and browning of white adipose tissue (WAT). Mice lacking CGI-58 in both BAT and WAT were cold sensitive, but only in the fasted state. Thus, LD lipolysis in BAT is not essential for cold-induced nonshivering thermogenesis in vivo. Rather, CGI-58-dependent LD lipolysis in BAT regulates WAT thermogenesis, and our data uncover an essential role of WAT lipolysis in fueling thermogenesis during fasting. PMID- 28988825 TI - PGC-1alpha Promotes Breast Cancer Metastasis and Confers Bioenergetic Flexibility against Metabolic Drugs. AB - Metabolic adaptations play a key role in fueling tumor growth. However, less is known regarding the metabolic changes that promote cancer progression to metastatic disease. Herein, we reveal that breast cancer cells that preferentially metastasize to the lung or bone display relatively high expression of PGC-1alpha compared with those that metastasize to the liver. PGC-1alpha promotes breast cancer cell migration and invasion in vitro and augments lung metastasis in vivo. Pro-metastatic capabilities of PGC-1alpha are linked to enhanced global bioenergetic capacity, facilitating the ability to cope with bioenergetic disruptors like biguanides. Indeed, biguanides fail to mitigate the PGC-1alpha-dependent lung metastatic phenotype and PGC-1alpha confers resistance to stepwise increases in metformin concentration. Overall, our results reveal that PGC-1alpha stimulates bioenergetic potential, which promotes breast cancer metastasis and facilitates adaptation to metabolic drugs. PMID- 28988823 TI - FGF19, FGF21, and an FGFR1/beta-Klotho-Activating Antibody Act on the Nervous System to Regulate Body Weight and Glycemia. AB - Despite the different physiologic functions of FGF19 and FGF21 as hormonal regulators of fed and fasted metabolism, their pharmacologic administration causes similar increases in energy expenditure, weight loss, and enhanced insulin sensitivity in obese animals. Here, in genetic loss-of-function studies of the shared co-receptor beta-Klotho, we show that these pharmacologic effects are mediated through a common, tissue-specific pathway. Surprisingly, FGF19 and FGF21 actions in liver and adipose tissue are not required for their longer-term weight loss and glycemic effects. In contrast, beta-Klotho in neurons is essential for both FGF19 and FGF21 to cause weight loss and lower glucose and insulin levels. We further show an FGF21 mimetic antibody that activates the FGF receptor 1/beta Klotho complex also requires neuronal beta-Klotho for its metabolic effects. These studies highlight the importance of the nervous system in mediating the beneficial weight loss and glycemic effects of endocrine FGF drugs. PMID- 28988826 TI - Clinical diagnostic tools for vitamin D assessment. AB - Vitamin D deficiency has been implicated in a plethora of diseases including rheumatoid arthritis, Parkinson's disease, Alzheimer's disease, and osteoporosis. Deficiency of this vitamin is a global epidemic affecting both developing and developed nations. Within a clinical context, the qualitative and quantitative analysis of vitamin D is therefore vital. The main metabolic markers for assessing vitamin D status in humans are the hydroxylated forms of vitamin D, 25OHD3 and 25OHD2 on account of their long half-lives within the body and excellent stability. An adequate level for healthy individuals of these hydroxylated forms is estimated to be around 20-40ng/ml of blood. There are three main analytical techniques for determining the levels of 25OHD3 and 25OHD2. The first technique is immunoassay-based and can be performed in a rapid, high throughput, automated manner, allowing as many as 240 tests per hour with the duration of each assay as little as 18min. Furthermore, it offers excellent sensitivity with a detection range of 3.4-156ng/ml. A major downside of immunoassays is that they are unable to distinguish between the various forms of vitamin D. While HPLC is a highthroughput low cost instrument it is not a very sensitive technique and cannot quantify the down stream metabolites of vitamin D. The third technique, namely liquid chromatography-mass spectrometry (LC-MS/), provides excellent sensitivity with a wide dynamic range from 0.068pg/ml to 100ng/ml. Additionally, it offers a high level of separation and permits identification of vitamin D-related metabolites. However, a huge limitation with LC/MS/MS is their poor throughput for sample analyses. As yet, there is no analytical technique which combines the fine detection capabilities of LC/MS/MS and the rapid, automated format of immunoassay, for vitamin D analyses. Future attention therefore needs to be given to this area if the current clinical diagnostic tools for vitamin D analysis are to be further improved. PMID- 28988824 TI - Citrobacter rodentium Subverts ATP Flux and Cholesterol Homeostasis in Intestinal Epithelial Cells In Vivo. AB - The intestinal epithelial cells (IECs) that line the gut form a robust line of defense against ingested pathogens. We investigated the impact of infection with the enteric pathogen Citrobacter rodentium on mouse IEC metabolism using global proteomic and targeted metabolomics and lipidomics. The major signatures of the infection were upregulation of the sugar transporter Sglt4, aerobic glycolysis, and production of phosphocreatine, which mobilizes cytosolic energy. In contrast, biogenesis of mitochondrial cardiolipins, essential for ATP production, was inhibited, which coincided with increased levels of mucosal O2 and a reduction in colon-associated anaerobic commensals. In addition, IECs responded to infection by activating Srebp2 and the cholesterol biosynthetic pathway. Unexpectedly, infected IECs also upregulated the cholesterol efflux proteins AbcA1, AbcG8, and ApoA1, resulting in higher levels of fecal cholesterol and a bloom of Proteobacteria. These results suggest that C. rodentium manipulates host metabolism to evade innate immune responses and establish a favorable gut ecosystem. PMID- 28988827 TI - Self as Object: Emerging Trends in Self Research. AB - Self representation is fundamental to mental functions. While the self has mostly been studied in traditional psychophilosophical terms ('self as subject'), recent laboratory work suggests that the self can be measured quantitatively by assessing biases towards self-associated stimuli ('self as object'). Here, we summarize new quantitative paradigms for assessing the self, drawn from psychology, neuroeconomics, embodied cognition, and social neuroscience. We then propose a neural model of the self as an emerging property of interactions between a core 'self network' (e.g., medial prefrontal cortex; mPFC), a cognitive control network [e.g., dorsolateral (dl)PFC], and a salience network (e.g., insula). This framework not only represents a step forward in self research, but also has important clinical significance, resonating recent efforts in computational psychiatry. PMID- 28988828 TI - Epigenetics and cardiovascular regenerative medicine in the elderly. AB - Cardiovascular disease (CVD) is a recognized age-dependent condition whose incidence is set to increase due to the gradual aging of the population. Moreover, ischemic cardiovascular diseases (i.e. stroke, myocardial infarction, critical limb ischemia) requiring blood vessel growth are associated with a worse outcome in elderly patients. Therefore, understanding the molecular cues regulating the vascular repair process is of paramount importance to prevent undesirable cardiovascular complications in this setting. A growing body of evidence suggests that epigenetic modifications - changes to the genome that do not involve changes in DNA sequence - may significantly derail gene expression trajectories during the life course, thus affecting molecular phenotype and functionality of angiogenic cells, namely mature endothelial cells (ECs), endothelial progenitor cells (EPCs), and bone-marrow (BM)-derived angiogenic cells. In the present review, we discuss the emerging role of epigenetics in age related impairment of the angiogenic process. Specifically, the following aspects are critically addressed: i) defective angiogenic process in aging; ii) impact of epigenetics (DNA methylation, histone modifications, microRNAs, long noncoding RNAs) on phenotype and function of ECs and BM-derived angiogenic cells; iii) clinical perspectives on epigenetic biomarkers and reprogramming approaches for autologous transplantation. A scrutiny characterization of the "old epigenome" may provide unprecedented insights to develop preventive strategies and regenerative therapeutic interventions in the elderly. PMID- 28988829 TI - Age related prefrontal compensatory mechanisms for inhibitory control in the antisaccade task. AB - Cognitive decline during aging includes impairments in frontal executive functions like reduced inhibitory control. However, decline is not uniform across the population, suggesting individual brain response variability to the aging process. Here we tested the hypothesis, within the oculomotor system, that older adults compensate for age-related neural alterations by changing neural activation levels of the oculomotor areas, or even by recruiting additional areas to assist with cognitive performance. We established that the observed changes had to be related to better cognitive performance to be considered as compensatory. To probe this hypothesis we used the antisaccade paradigm and analyzed the effect of aging on brain activations during the inhibition of prepotent responses to visual stimuli. While undergoing a fMRI scan with concurrent eye tracking, 25 young adults (21.7 y/o +/- 1.9 SDM) and 25 cognitively normal older adults (66.2 y/o +/- 9.8 SDM) performed an interleaved pro/antisaccade task consisting of a preparatory stage and an execution stage. Compared to young adults, older participants showed a larger increase in antisaccade reaction times, while also generating more antisaccade direction errors. BOLD signal analyses during the preparatory stage, when response inhibition processes are established to prevent an automatic response, showed decreased activations in the anterior cingulate and the supplementary eye fields in the older group. Moreover, older adults also showed additional recruitment of the frontal pole not seen in the younger group, and larger activations in the dorsolateral prefrontal cortex during antisaccade preparation. Additional analyses to address the performance variability in the older group showed distinct behavioral-BOLD signal correlations. Larger activations in the saccade network, including the frontal pole, positively correlated with faster antisaccade reaction times, suggesting a functional recruitment of this area. However, only the activation in the dorsolateral prefrontal cortex during the antisaccade events showed a negative correlation with the number of errors across older adults. These findings support the presence of two dissociable age-related plastic mechanisms that result in different behavioral outcomes. One related to the additional recruitment of neural resources within anterior pole to facilitate modulation of cognitive responses like faster antisaccade reaction times, and another related to increased activation of the dorsolateral prefrontal cortex resulting in a better inhibitory control in aging. PMID- 28988830 TI - Effects of neonatal deafness on resting-state functional network connectivity. AB - Normal brain development depends on early sensory experience. Behavioral consequences of brain maturation in the absence of sensory input early in life are well documented. For example, experiments with mature, neonatally deaf human or animal subjects have revealed improved peripheral visual motion detection and spatial localization abilities. Such supranormal behavioral abilities in the nondeprived sensory modality are evidence of compensatory plasticity occurring in deprived brain regions at some point or throughout development. Sensory deprived brain regions may simply become unused neural real-estate resulting in a loss of function. Compensatory plasticity and loss of function are likely reflected in the differences in correlations between brain networks in deaf compared with hearing subjects. To address this, we used resting-state functional magnetic resonance imaging (fMRI) in lightly anesthetized hearing and neonatally deafened cats. Group independent component analysis (ICA) was used to identify 20 spatially distinct brain networks across all animals including auditory, visual, somatosensory, cingulate, insular, cerebellar, and subcortical networks. The resulting group ICA components were back-reconstructed to individual animal brains. The maximum correlations between the time-courses associated with each spatial component were computed using functional network connectivity (FNC). While no significant differences in the delay to peak correlations were identified between hearing and deaf cats, we observed 10 (of 190) significant differences in the amplitudes of between-network correlations. Six of the significant differences involved auditory-related networks and four involved visual, cingulate, or somatosensory networks. The results are discussed in context of known behavioral, electrophysiological, and anatomical differences following neonatal deafness. Furthermore, these results identify novel targets for future investigations at the neuronal level. PMID- 28988831 TI - Calcification remodeling index assessed by cardiac CT predicts severe coronary stenosis in lesions with moderate to severe calcification. AB - OBJECTIVES: To assess the diagnostic performance of the calcification remodeling index (RI) as assessed by coronary computed tomography angiography (coronary CTA) to predict the presence of severe coronary stenosis in atherosclerotic coronary lesions with moderate to severe calcification. METHODS: Patients who underwent coronary CTA and invasive coronary angiography (ICA) within one month and had moderately to severely calcified lesions as revealed by coronary CTA, were retrospectively included. The calcification RI was calculated as the ratio of the cross-sectional lumen area (with inclusion of calcium area) of the most severely calcified site to the proximal reference lumen area. Other parameters, such as the calcium volume, regional Agatston score, calcification length, involved calcium arc quadrants and CTA-assessed diameter stenosis, were also recorded. A multivariate model was used to identify the variables that predict the presence of severe coronary stenosis (diameter stenosis ? 70%) as determined by ICA. RESULTS: 422 patients with 629 lesions were finally included in the study. Lesions with severe stenoses as determined by ICA tended to have larger calcium volumes, regional Agatston scores, CTA-assessed diameter stenoses, longer calcium length, more involved calcium arc quadrants and a significantly smaller calcification remodeling index. ROC curve analysis determined the best cutoff value of the calcification RI as 0.94 (AUC = 0.816, p < 0.001), which yielded highest diagnostic accuracy (83.3%, 524/629) to identify severe coronary stenosis. Among all parameters, calcification RI ?0.94 is the strongest independent predictor (odds ratio: 17.5, p < 0.001) of severe coronary stenosis. CONCLUSIONS: With an optimalcut-off value of 0.94, calcification RI is the strongest independent predictor of severe coronary stenosis in calcified coronary atherosclerotic lesions. PMID- 28988832 TI - Effect of inoculum on the anaerobic digestion of food waste accounting for the concentration of trace elements. AB - The production of renewable energy in the form of methane from the anaerobic digestion (AD) of food waste (FW) varies depending on factors such as the quantity and quality of the inoculum. This research evaluated the influence of trace elements (Ca, K, Fe, Zn, Al, Mg, Co, Ni, and Mo) present in inoculum from different sources (wastewater treatment plants (WWTPs): 2 agro-industrial WWTPs and 1 municipal WWTP) on the AD of FW. This study found that the source of the inoculum determines the content of macronutrients and trace elements, which can alter the requirements of the AD process and therefore affect methane production. The inoculum obtained from municipal WWTPs contain potentially inhibitory concentrations of Zn and Al that negatively affect methane production (<70 mL CH4.gVS-1), the hydrolysis constant (<0.19 d-1), and the lag-phase (>7 days). It was also found that high concentrations of trace elements such as Ni (35.2 mg kg 1) and Mo (15.4 mg kg-1) in the inoculum increase methane production (140.7 mL CH4.gVS-1) and hydrolysis constant (>0.18d-1) in addition to presenting short lag phase (<1 day) in the AD of food waste. PMID- 28988833 TI - eHomecare and safety: The experiences of older patients and their relatives. AB - The study's aim was to extend descriptions of how older patients with granted eHomecare and their relatives understand safety, and further to describe how they experience safety in everyday life. The study was conducted in Sweden. The participants were 12 older patients who had been provided with eHomecare and 8 relatives. Data were collected by semi-structured individual interviews. A conceptual framework of safety was used and a qualitative content analysis was conducted in a deductive and an inductive phase. The deductive results are presented in predefined categories: perceived sense of safety, disturbance and threats, re-establishing safety, and new safety. The inductive analysis resulted in two main categories: safety as part of everyday life and eHomecare as safety. The results show that eHomecare can promote safety for older patients and their relatives. Existing doubts and ethical concerns about the service can be minimized by providing adequate information. PMID- 28988834 TI - Predictive model for health-related quality of life in patients with Parkinson's disease. AB - This study was conducted to develop and test a prediction model that explains health-related quality of life (HRQoL) of patients with Parkinson's disease (PD). Participants were 248 patients with PD enrolled in the neurology clinic of a university hospital in Seoul, Korea. The data were collected through structured questionnaires from March 1 to July 5, 2013. Motor fluctuations, depression, sleep disturbances, fatigue, and activities of daily living had significant direct effects on the quality of life of PD patients. Disease severity, social support, pain, sleep disturbances, fatigue, and activities of daily living had significant indirect effects on patients' quality of life. These predictive variables explained 77.4% of the total variance. The assessment of HRQoL in PD should be considered along with the variables affecting it, including social support. In addition, strategies to enhance social support may be useful for improving the quality of life for patients with PD. PMID- 28988835 TI - INTERACT in VA Community Living Centers (CLCs): Training and Implementation Strategies. AB - Studies have shown that hospitalizations of nursing home (NH) residents lead to complications and poorer quality of life. The Interventions to Reduce Acute Care Transfers (INTERACT) Quality Improvement (QI) Program assists licensed NH staff in avoiding such hospitalizations. INTERACT aims to improve the management of acute changes in residents' conditions by providing tools to help staff recognize subtle changes in condition, improve communication, and implement QI strategies. INTERACT has been vetted by national clinical leaders and experts in long term care (LTC). Multiple NHs have implemented INTERACT and it has been adopted in Canada, the United Kingdom, and Singapore. QI initiatives involve adaptation to the organizational context in which it is being implemented. We report adaptation of the INTERACT QI program and implementation training into Veteran Affairs (VA) Community Living Centers (CLCs) (VA equivalent NH) and summarize the efforts to introduce and train nursing leadership to integrate the intervention into selected CLCs. PMID- 28988837 TI - Nutrition Care Process and Model Update: Toward Realizing People-Centered Care and Outcomes Management. PMID- 28988836 TI - Parental Perceptions, Risks, and Incidence of Pediatric Unintentional Injuries. AB - INTRODUCTION: More than 9,000 children die annually from various causes of unintentional injury. Of all the pediatric unintentional injuries occurring in the United States, 8.7 million are treated in emergency departments, and 225,000 require hospitalization annually. Health education programs are available to address these injuries. The objective of this research was to examine the distribution of self-reported high priority injury risks in an urban Midwestern pediatric level 1 trauma center and investigate the relationship between parental perceptions and injury-prevention behaviors. Prevalence rates for 3 data sources are compared. METHODS: Missouri Information for Community Assessment (MICA) was categorized to mirror variables corresponding with risks of injury presented in the Safe 'n' Sound (SNS) program. Level 1 trauma center data were examined to determine how the variables were distributed compared with MICA data and with the parent-reported levels. RESULTS: A total of 429 SNS surveys were compared with ED data and MICA data. For SNS users, car crashes were identified as the highest risk, specifically due to the use of incorrect car seats. The injuries seen most often in the emergency department were falls, and falls were also the most prevalent injury captured by MICA. Controlling for demographics, parental perceptions predicted several risks for injury. DISCUSSION: Because parental perceptions are significantly related to risks of injury, prevention programs aiming to decrease injuries could focus on the perceptions. Not only can perceptions be used to tailor health communication materials, these perceptions can be the targets of change. Further work might investigate the extent to which changes in perceptions result in increased adoption of safety practices. PMID- 28988838 TI - Staff Food-Related Behaviors and Children's Tastes of Food Groups during Lunch at Child Care in Oklahoma. AB - BACKGROUND: Young children should consume a variety of nutrient-dense foods to support growth, while limiting added fat and sugar. A majority of children between the ages of 3 and 5 years attend child care in the United States, which makes this environment and the child-care staff influential at meals. OBJECTIVE: The aim was to determine the association between best-practice food-related behaviors and young children's tastes of fruit, vegetable, low-fat dairy, and high-fat/high-sugar foods at child care. DESIGN: This was a cross-sectional study. PARTICIPANTS: A community-based study with 201 children ages 3 to 5 years from 25 early care and education centers, including 11 tribally affiliated centers and two Head Start programs across Oklahoma. Data collection occurred from fall 2011 to spring 2014. MAIN OUTCOME MEASURES: Classroom observations used the Environmental Policy Assessment Observation tool to measure the staff behaviors and environment. Staff behavior was compared at three different levels: the composite score of staff nutrition behavior, each constituent staff behavior, and staff behaviors grouped into broader feeding behaviors. Tasted food was measured through the Dietary Observation in Child Care method. The children's meals were categorized into the following food groups: fruit, vegetable, low-fat dairy, fried vegetable, fried meat, high-fat meat, and high-fat/high-sugar food. STATISTICAL ANALYSIS PERFORMED: Descriptive statistics were calculated for relevant variables. Relationships between the constituent staff behaviors and food groups that children tasted were compared using multilevel mixed-model analysis. RESULTS: The mean number of tasted fruit or vegetable items was higher and the mean number of tasted high-fat/high-sugar food items was lower when staff: 1) determined fullness before plate removal when less than half of food was eaten, 2) ate with the children, 3) and talked about healthy food. CONCLUSIONS: The utilization of the three staff behaviors and their association with higher mean tastes of nutrient-dense items and lower mean tastes of high fat/high-sugar food items among exposed children demonstrated support for the use of the best practices in early care and education centers. PMID- 28988839 TI - Trends in Fast-Food and Sugar-Sweetened Beverage Consumption and Their Association with Social Environmental Status in South Korea. AB - BACKGROUND: As South Korea has enjoyed rapid economic development, Koreans' diet, particularly consumption of fast food (FF) and sugar-sweetened beverages (SSBs), has changed. OBJECTIVE: To examine time trends in FF and SSB consumption and their associations with social environmental status (SEnS) in South Korea. DESIGN: Korean National Health and Nutrition Examination Surveys (KNHANES) were a series of population-based cross-sectional surveys. PARTICIPANTS: Data from the KNHANES conducted in 1998, 2001, 2005, and 2007-2009 for 49,826 Koreans aged >=1 year were used. MAIN OUTCOME MEASURES: Consumption of FF and SSBs were assessed by a 24-hour recall. We defined two FF categories (Western-style and Korean style) and one SSB category. Sex, age, household income, and residence regions were investigated. STATISTICAL ANALYSES PERFORMED: The primary sampling units, strata, and sampling weights were taken into account using SAS survey-related procedures. Logistic regression models were used to test associations between SEnS and FF consumption. RESULTS: Over an 11-year period, the proportion of participants' who consumed Western FF and SSBs on the surveyed day doubled (P<0.05). Per capita energy contribution from Western FF also increased in adults, men, and low-income groups. SSB consumption doubled (per capita: 32 to 82 kcal/day, only consumers: 123 to 166 kcal/day), but consumption of Korean-style FF decreased (P<0.05). Compared with the low-income rural resident group, the high-income urban resident group was much more likely to consume Western FF (OR=26.7[3.7, 193.4]) and SSBs (odds ratio [OR]=3.1 [2.4, 4.1]) in 1998. However, in recent years, the patterns changed; the high-income urban resident group was more likely to consume Korean-style FF (OR=2.0[1.3, 2.9]) and SSBs (OR=1.7[1.3, 2.1]). CONCLUSIONS: In South Korea, people who reported consuming Western FF and SSBs on the surveyed day almost doubled during 1998-2009, whereas those who consumed Korean FF decreased. SEnS was related to FF and SSB consumption. PMID- 28988840 TI - Mechanism of co-aggregation in a protein mixture with small additives. AB - Co-aggregation plays an important role in processing protein-rich food materials under heterogeneous conditions. The main cause of co-aggregation is an electrostatic attraction between oppositely charged molecules. This study investigated thermal aggregation of beta-lactoglobulin (BLG) (pI=5.1) and lysozyme (LYZ) (pI=10.7) as a model for the heterogeneous conditions of a protein solution. BLG and LYZ were more aggregated in the mixture than in the single solutions. Co-aggregation of the BLG-LYZ mixture was not observed below 60 degrees C at which temperature BLG and LYZ retained their native structures. Adding sugars, salts, or amino acids to the BLG-LYZ mixture during the heat treatment revealed the co-aggregation process as follows. (i) All additives tested suppressed both the nucleation and growth of aggregates. (ii) Salts affected nucleation stage to the same degree, except arginine hydrochloride (Arg). (iii) Arg specifically suppressed both nucleation and growth of aggregates. These results indicate that co-aggregation in a protein mixture is more sensitive to the partial unfolding of proteins than that in a single protein solution, due to the presence of electrostatic attraction between different molecules. These results provide new insight into protein aggregation as well as the molecular mechanism of additives under heterogeneous conditions. PMID- 28988841 TI - Adsorption of Cu(II), Cd(II), Hg(II), Pb(II) and Zn(II) from aqueous single metal solutions by guanyl-modified cellulose. AB - A novel chemically guanyl-modified cellulose (Gu-MC) - material has been synthesized for the adsorption of Cu2+, Cd2+, Hg2+, Pb2+ and Zn2+ metal ions from aqueous solution. Cellulose was pretreated with periodate prior to its condensation with aminoguanidine for the formation of cellulose aldehyde-guanyl Schiff's. The synthesized material was characterized by Fourier transform infrared spectra (FTIR), elemental analysis, scanning electron microscope (SEM) and thermogravimetric analysis (TGA). Moreover, the effect of contact time, pH, adsorbent dosage, interfering ions and initial concentration of metal ions on the adsorption capacity were investigated. At optimum conditions, the adsorption capacities of Cu2+, Zn2+, Cd2+, Pb2+ and Hg2+ were 83, 78, 68, 52, and 48mgg-1, respectively. The kinetic of adsorption adopted to the second-order model and kinetic model showed that the chemical adsorption is the rate limiting step. The proposed material has been successfully applied for the adsorption of the target metal ions from different real samples with satisfactory results. PMID- 28988842 TI - A novel core 1 O-linked glycan-specific binding lectin from the fruiting body of Hericium erinaceus. AB - Mucin-type O-glycans are involved in biological functions on the cell surface as well as the glycoproteins and can also be used as specific carbohydrate biomarkers of many diseases. In this study, I purified a novel core 1 O-linked glycan specific lectin, Hericium erinaceus lecin (HeL), from the fruiting body of the mushroom Hericium erinaceus, which is known as the natural source for a sialic acid-binding lectin. Upon optimization of the purification conditions, a sequence of ion exchange, affinity, ion exchange, and size-exclusion chromatography resulted in the highest yield and best quality of lectin without protease activity. The resulting purified HeL is an apparent hexameric protein with a subunit molecular weight of 15kDa, and a pI of 4.3. In hemagglutination inhibition assay, the purified lectin was only inhibited by glycoproteins containing mucin-type O-glycans and reacted weakly with Galbeta(1,3)GalNAc. Glycan array analyses showed that HeL specifically interacts with core 1 O-linked glycans as well as extended O-glycan structures containing sialylation or fucosylation. The glycan binding specificity of HeL is comparable to that of peanut agglutinin for detection of a broader range of extended core 1 O-glycan structures. Taken together, these results provide an efficient and optimized procedure for the purification of HeL from the fruiting body of the mushroom Hericium erinaceus. Moreover, HeL represents a powerful tool for analyzing core 1 and extended core 1 O- glycan structures in diagnosis assays. PMID- 28988843 TI - Fabrication of cellulose acetate nanocomposite membranes using 2D layered nanomaterials for macromolecular separation. AB - Cellulose acetate (CA) nanocomposite ultrafiltration (UF) membranes were fabricated using 2D layered nanosheets such as graphene oxide (GO) and exfoliated molybdenum disulfide (E-MoS2) and effectively used for the removal of macromolecular protein. The GO and E-MoS2 nanosheets were prepared and characterized by FT-IR and XRD respectively. GO and E-MoS2 (0.5wt.%) were blended individually with CA. The assenting changes generated by the incorporation of GO and E-MoS2 in terms of surface hydrophilicity of the nanocomposite membrane were analyzed by pure water flux (PWF) and contact angle measurement. The influence of 2D nanosheets on the morphology of CA are studied by scanning electron microscopy (SEM). Mechanical strength and hydraulic resistance of the nanocomposite membranes were found to be improved compared to bare CA membrane. The separation and antifouling performance of the nanocomposite membranes were studied using macromolecular bovine serum albumin (BSA). From the results, it was observed that a CA/GO-0.5 membrane exhibited the highest PWF (125.4+/-1.7Lm-2h-1), water content (70.6+/-1.2%), porosity (34.6+/-1.7%), flux recovery ratio (FRR) (88.8+/ 1.6%) and lowest contact angle (63.9+/-2.5 degrees ), hydraulic resistance (4.3+/ 0.67kPa/Lm-2h -1) than pure CA and CA/E-MoS2-0.5 membranes. CA/GO-0.5 membrane displayed superior UF and antifouling performance due to the greater affinity of GO nanoparticles towards water. PMID- 28988844 TI - Sono-chemical synthesis of cellulose nanocrystals from wood sawdust using Acid hydrolysis. AB - Cellulose nanocrystal (CNC) is a unique material obtained from naturally occurring cellulose fibers. Owing to their mechanical, optical, chemical, and rheological properties, CNC gained significant interest. Herein, we investigate the potential of commercially non-recyclable wood waste, in particular, sawdust as a new resource for CNC. Isolation of CNC from sawdust was conducted as per acid hydrolysis which induced by ultrasonication technique. Thus, sawdust after being alkali delignified prior sodium chlorite bleaching, was subjected to sulfuric acid with concentration of 65% (w/w) at 60 degrees C for 60min. After complete reaction, CNC were collected by centrifugation followed by dialyzing against water and finally dried via using lyophilization technique. The CNC yield attained values of 15% from purified sawdust. Acid hydrolysis mechanism exactly referred that, the amorphous regions along with thinner as well as shorter crystallites spreaded throughout the cellulose structure are digested by the acid leaving CNC suspension. The latter was freeze-dried to produce CNC powder. A thorough investigation pertaining to nanostructural characteristics of CNC was performed. These characteristics were monitored using TEM, SEM, AFM, XRD and FTIR spectra for following the changes in functionality. Based on the results obtained, the combination of sonication and chemical treatment was great effective in extraction of CNC with the average dimensions (diameter*length) of 35.2+/-7.4nm*238.7+/-81.2nm as confirmed from TEM. Whilst, the XRD study confirmed the crystal structure of CNC is obeyed cellulose type I with crystallinity index ~90%. Cellulose nanocrystals are nominated as the best candidate within the range studied in the area of reinforcement by virtue of their salient textural features. PMID- 28988845 TI - A Bombyx homolog of ovo is a segmentation gene that acts downstream of Bm wnt1(Bombyx wnt1 homolog). AB - Insect embryogenesis is divided into long and short/intermediate germ types. The long germ type may exhibit Drosophila-like hierarchical segmentation mechanisms, whereas the short/intermediate type assumes some repeating mechanisms that are considered to be ancestral. Embryogenesis in Bombyx mori possesses both characteristics. Here, Bombyx ovo homolog (Bm-ovo) was identified as a gene involved in segmentation. Ovo is a Drosophila gene that encodes a zinc finger transcription factor and studies on its homolog functions in other systems have suggested that it acts as a switch to enable the initiation of differentiation from a progenitor cell state. This is the first description for ovo homologs being involved in insect segmentation. Bm-ovo is expressed dynamically during embryogenesis in a pattern that resembles that of gap and pair-rule genes. In Bm ovo RNAi knockdown embryos, posterior segmentation does not proceed. In addition, defects in anterior segments are observed. In Bm-wnt1 knockdown embryos, the Bm ovo expression pattern was changed, suggesting that Bm-wnt1 is an upstream regulator of Bm-ovo. The involvement of Bm-ovo may represent a novel ancestral step under the control of wnt genes in insect segmentation: this step may resemble those operating in cell differentiation processes. PMID- 28988846 TI - Facial nerve neuroma in the geniculate ganglion extending into the internal auditory canal: A case report. AB - Facial nerve schwannoma is a very rare benign tumor representing less than 1% of intrapetrous lesions. Our patient is a forty-one year old female who has suffered from recurrent right facial palsy for the last six years. She was first misdiagnosed as having Bell's palsy and received corticosteroids which resulted in little improvement. She then had facial nerve decompression surgery which resulted in a partial improvement. Since then, she has suffered from recurrent attacks of facial palsy. Two years ago, she came to our hospital seeking further treatment options. The final diagnosis made by MRI was a possible facial nerve tumor. To obtain a better facial outcome, total tumor removal was performed through the middle cranial fossa approach along with facial-hypoglossal nerve end to-side anastomosis through transmastoid approach. Her hearing was preserved, and she obtained a better facial outcome than that of her preoperative level. In conclusion, facial nerve schwannoma has the potential to be misdiagnosed as Bell's palsy which might lead to a delay in diagnosis, and end-to-side neurorrhaphy may be an effective alternative in a selected case. PMID- 28988847 TI - Impact of bacteremia prediction rule in CAP: Before and after study. AB - OBJECTIVE: In cases of community acquired pneumonia (CAP), it has been known that blood cultures have low yields and rarely affect clinical outcomes. Despite many studies predicting the likelihood of bacteremia in CAP patients, those results have been rarely implemented in clinical practice, and use of blood culture in CAP is still increasing. This study evaluated impact of implementing a previously derived and validated bacteremia prediction rule. METHODS: In this registry-based before and after study, we used piecewise regression analysis to compare the blood culture rate before and after implementation of the prediction rule. We also compared 30-day mortality, emergency department (ED) length of stay, time interval to initial antibiotics after ED arrival, and any changes to the antibiotics regimen as results of the blood cultures. In subgroup analysis, we compared two groups (with or without the use of the prediction rule) after implementation period, using propensity score matching. RESULTS: Following the implementation, the blood culture rate declined from 85.5% to 78.1% (P=0.003) without significant changes in 30-day mortality and antibiotics regimen. The interval to initial antibiotics (231min vs. 221min, P=0.362) and length of stay (1019min vs. 954min, P=0.354) were not significantly changed. In subgroup analysis, the group that use the prediction rule showed 25min faster antibiotics initiation (P=0.002) and 48min shorter length of stay (P=0.007) than the group that did not use the rule. CONCLUSION: Implementation of the bacteremia prediction rule in CAP patients reduced the blood culture rate without affecting the 30-day mortality and antibiotics regimen. PMID- 28988848 TI - ED utilization of medical clearance testing for psychiatric admission: National Hospital Ambulatory Medical Care Survey analysis. AB - INTRODUCTION: Routine medical clearance testing of emergency department (ED) patients with acute psychiatric illnesses in the absence of a medical indication has minimal proven utility. Little is known about the variations in clinical practice of ordering medical clearance tests. METHODS: This study was an analysis of data from the annual United States National Hospital Ambulatory Medical Care Survey from 2010 to 2014. The study population was defined as ED visits by patients >=18years old admitted to a psychiatric facility. We sought to determine the percentage of these ED visits in which at least one medical clearance test was ordered. Using a multivariate logistic regression model, we also evaluated whether patient visit factors or regional variation was associated with use of medical clearance tests. RESULT: A medical clearance test was ordered in 80.4% of ED visits ending with a psychiatric admission. Multivariate logistic regression demonstrated a statistically significant increased odds ratio (OR) of medical clearance testing based on age (OR 1.02, 95%CI 1.01, 1.03), among visits involving an injury or poisoning (OR 2.38, 95%CI 1.54, 3.68), and in the Midwest region as compared to the Northeast region (OR 2.2, 95% confidence interval [CI] 1.09, 4.46), after adjusting for other predictors. DISCUSSION: Our study demonstrated that, on a national level, 4 out of 5 ED visits resulting in a psychiatric facility admission had a medical clearance test ordered. Future research is needed to investigate the reasons underlying the discrepancies in ordering patterns across the U.S., including the effect of local psychiatric admission policies. PMID- 28988850 TI - Biomarker Potential of Extracellular miRNAs in Duchenne Muscular Dystrophy. AB - miRNAs are small, noncoding RNAs that not only regulate gene expression within cells, but might also constitute promising extracellular biomarkers for a variety of pathologies, including the progressive muscle-wasting disorder Duchenne Muscular Dystrophy (DMD). A set of muscle-enriched miRNAs, the myomiRs (miR-1, miR-133, and miR-206) are highly elevated in the serum of patients with DMD and in dystrophin-deficient animal models. Furthermore, circulating myomiRs might be used as pharmacodynamic biomarkers, given that their levels can be restored towards wild-type levels following exon skipping therapy in dystrophic mice. The relationship between muscle pathology and extracellular myomiR release is complex, and incompletely understood. Here, we discuss current progress leading towards the clinical utility of extracellular miRNAs as putative DMD biomarkers, and their possible contribution to muscle physiology. PMID- 28988849 TI - Oxygen, Metabolism, and Regeneration: Lessons from Mice. AB - The discovery that the Murphy Roths Large (MRL) mouse strain is a fully competent, epimorphic tissue regenerator, proved that the machinery of regeneration was preserved through evolution from hydra, to salamanders, to mammals. Such concepts have allowed translation of the biology of amphibians, and their ability to regenerate, to a mammalian context. We identified the ancient hypoxia-inducible factor (HIF)-1alpha pathway, operating through prolyl hydroxylase domain proteins (PHDs), as a central player in mouse regeneration. Thus, the possibility of targeting PHDs or other HIF-1alpha modifiers to effectively recreate the amphibian regenerative state has emerged. We posit that these regenerative pathways are critical in mammals. Moreover, the current approved use of PHD inhibitors in the clinic should allow fast-track translation from mouse studies to drug-based regenerative therapy in humans. PMID- 28988851 TI - Ablation of C-fibers decreases quantal size of GABAergic synaptic transmission in the insular cortex. AB - The primary sensory cortex exhibits neuroplastic changes responding to sensory disturbances, and GABAergic synaptic transmission plays a critical role in the regulation of plasticity. The insular cortex (IC) integrates orofacial nociceptive signals conveyed via myelinated Adelta- and unmyelinated C-fibers. However, it has been unknown whether a disturbance of nociceptive inputs, such as a deletion of the peripheral nerves, alters GABAergic local circuit in IC. The present study elucidated GABAergic synaptic transmission in the model rat whose C fibers were ablated by capsaicin injection 1-2 days after birth. In vivo optical imaging revealed that capsaicin-treated rats showed a facilitative excitatory propagation in IC responding to dental pulp stimulation. Whole-cell patch-clamp recording from pyramidal neurons (Pyr) demonstrated that capsaicin-treated rats showed the smaller amplitude of miniature inhibitory postsynaptic currents (IPSCs) than sham-treated rats without changing the frequency. Furthermore, replacement of extracellular Ca2+ to Sr2+, which induces an asynchronous release of neurotransmitters in the quantal size, induced a smaller amplitude of asynchronous unitary IPSCs recorded from fast-spiking GABAergic interneuron to Pyr connections in capsaicin-treated rats than sham-treated rats. These results suggest that capsaicin treatment depresses IPSCs via a postsynaptic mechanism. To confirm this possibility, the variance-mean analysis of unitary IPSCs was employed and we found that quantal size of GABAergic synaptic transmission was smaller in capsaicin-treated rats than in sham-treated rats. These results suggest that ablation of C-fibers induces plastic changes in GABAergic synaptic transmission by decreasing postsynaptic GABAA receptor-mediated conductance, which is a possible mechanism of the facilitative excitation in IC of capsaicin treated rats. PMID- 28988852 TI - Assessment of a nutritional supplement containing resveratrol, prebiotic fiber, and omega-3 fatty acids for the prevention and treatment of mild traumatic brain injury in rats. AB - Children and adolescents have the highest rates of traumatic brain injury (TBI), with mild TBI (mTBI) accounting for most of these injuries. Adolescents are particularly vulnerable and often suffer from post-injury symptomologies that may persist for months. We hypothesized that the combination of resveratrol (RES), prebiotic fiber (PBF), and omega-3 fatty acids (docosahexaenoic acid (DHA)) would be an effective therapeutic supplement for the mitigation of mTBI outcomes in the developing brain. Adolescent male and female Sprague-Dawley rats were randomly assigned to the supplement (3S) or control condition, which was followed by a mTBI or sham insult. A behavioral test battery designed to examine symptomologies commonly associated with mTBI was administered. Following the test battery, tissue was collected from the prefrontal cortex (PFC) and primary auditory cortex for Golgi-Cox analysis of spine density, and for changes in expression of 6 genes (Aqp4, Gfap, Igf1, Nfl, Sirt1, and Tau). 3S treatment altered the behavioral performance of sham animals indicating that dietary manipulations modify premorbid characteristics. 3S treatment prevented injury-related deficits in the longer-term behavior measures, medial prefrontal cortex (mPFC) spine density, and levels of Aqp4, Gfap, Igf1, Nfl, and Sirt1 expression in the PFC. Although not fully protective, treatment with the supplement significantly improved post-mTBI function and warrants further investigation. PMID- 28988853 TI - Ecological performance of construction materials subject to ocean climate change. AB - Artificial structures will be increasingly utilized to protect coastal infrastructure from sea-level rise and storms associated with climate change. Although it is well documented that the materials comprising artificial structures influence the composition of organisms that use them as habitat, little is known about how these materials may chemically react with changing seawater conditions, and what effects this will have on associated biota. We investigated the effects of ocean warming, acidification, and type of coastal infrastructure material on algal turfs. Seawater acidification resulted in greater covers of turf, though this effect was counteracted by elevated temperatures. Concrete supported a greater cover of turf than granite or high density polyethylene (HDPE) under all temperature and pH treatments, with the greatest covers occurring under simulated ocean acidification. Furthermore, photosynthetic efficiency under acidification was greater on concrete substratum compared to all other materials and treatment combinations. These results demonstrate the capacity to maximise ecological benefits whilst still meeting local management objectives when engineering coastal defense structures by selecting materials that are appropriate in an ocean change context. Therefore, mitigation efforts to offset impacts from sea-level rise and storms can also be engineered to alter, or even reduce, the effects of climatic change on biological assemblages. PMID- 28988854 TI - Dynamics of phytoplankton productivity and exopolysaccharides (EPS and TEP) pools in the Seine Estuary (France, Normandy) over tidal cycles and over two contrasting seasons. AB - Exopolysaccharides (EPS) play an important role in the carbon flux and may be directly linked to phytoplankton and microphytobenthos production, most notably in estuarine systems. However the temporal and spatial dynamics of estuarine EPS are still not well understood, nor how primary productivity triggers this variability at these different scales. The aim of this study was to investigate the primary productivity of phytoplankton and EPS dynamics in the Seine estuary over a tidal cycle in three different haline zones over two contrasted seasons. The other objectives was to investigate the origin of pools of soluble carbohydrates (S-EPS) and transparent exopolymeric particles (TEP) in phytoplankton, microphytobenthos or other compartments. High frequency measurements of productivity were made in winter and summer 2015. Physical and chemical parameters, biomass and EPS were measured at hourly intervals in sub surface waters and just above the water sediment-interface. Our results confirmed that high frequency measurements improve the accuracy of primary productivity estimations and associated carbon fluxes in estuaries. The photosynthetic parameters were shown to be strongly controlled by salinity and by the concentrations of suspended particle matter at the smallest temporal and at spatial scales. At these scales, our results showed an inverse relationship between EPS concentrations and biomass and productivity, and a positive relationship with sediment resuspension. Additionally, the distribution of EPS appears to be linked to hydrodynamics with the tide at daily scale and with the winter at seasonal scale. At spatial scale, the maximum turbidity zone played an important role in the distribution of TEP. Our results suggest that, in the Seine estuary, between 9% and 33% of the S-EPS pool in the water column can be attributed to phytoplankton excretion, while only 0.4%-1.6% (up to 6.14% in exceptional conditions) originates from the microphytobenthos compartments. Most EPS was attributed to remobilization of detrital carbon pools in the maximum turbidity zone and in the sediment or allochthonous origin. PMID- 28988855 TI - Grazing in adults with obesity and eating disorders: A systematic review of associated clinical features and meta-analysis of prevalence. AB - Grazing, the unstructured, repetitive eating of small amounts of food, is a pattern of eating which has been associated with negative outcomes following bariatric surgery. Less is known about grazing in eating disorders and in non surgical obese samples. This review aims to critically examine the existing research on the prevalence of grazing, associated treatment outcomes, and clinical correlates in adults with eating disorders and/or obesity, in clinical and community settings. A systematic electronic database search yielded 38 studies which met inclusion criteria for the review. A meta-analysis was conducted using prevalence data from 32 studies (31 datasets). Mean pooled prevalence in obesity (n=26 studies) was 33.20% (95% CI [27.54, 39.11]) at pre weight loss treatment, 28.16% (95% CI [17.86, 39.73]) at follow-up, and 23.32% (95% CI [3.07, 52.04]) in the community. Nine studies provided prevalence estimates in eating disorders: 58.25% (95% CI [52.75, 63.66]) in bulimia nervosa; 67.77% (95% CI [44.96, 87.13]) in binge eating disorder; and 34.31% (95% CI [26.56, 42.49]) in anorexia nervosa. The results suggest that grazing is widely prevalent within obesity and eating disorders. There is mixed evidence to suggest that grazing (especially a "compulsive" subtype including a sense of loss of control) is associated with poorer weight loss treatment outcomes in obesity, lower mood, increased eating disorder symptomatology, and decreased mental health related quality of life. Differences in the operationalisation of grazing may account for inconsistent findings in regards to specific correlates and risks associated with this behaviour; therefore, there is an urgent need to refine and adopt a consistent definition of grazing. PMID- 28988856 TI - A 3D-printed modular device for imaging the brain of small birds. AB - BACKGROUND: One potential barrier to using in vivo imaging in any new animal species is solving the basic problem of how to hold animals safely and securely during scans. NEW METHOD: In this paper, we describe the design, fabrication, use, and positional reproducibility of a 3D-printed plastic device (the Avian Imaging Device, or AID) for imaging the brain of 1 or 2 small songbirds. We designed two different types of head cones to use with this device: one that was not contoured and designed for anesthesia induction, and one contoured to the shape of a house sparrow head, designed to be used with a pre-anesthetized animal. RESULTS: Compared to no holder, using the AID with both contoured and non contoured head cones significantly reduced the amount of translation necessary to align the head in pairs of CT scans (by 78% and 90%, respectively); using the contoured head cone also significantly reduced the amount of rotation necessary for head alignment in registering pairs of scans (by 90%). COMPARISON WITH EXISTING METHOD(S): Using an animal holder that can not only securely hold animals but which has high positional reproducibility is essential to take advantage of the maximum resolution possible with small animal imaging. 3D printed materials are also compatible with PET and CT, environmentally stable, and fast and inexpensive to make. CONCLUSIONS: Researchers can learn from the design of the AID and use our CAD models as a starting point for fabricating devices for multiple small-animal imaging needs. PMID- 28988857 TI - Viscoelastic Dissipation Stabilizes Cell Shape Changes during Tissue Morphogenesis. AB - Tissue morphogenesis relies on the production of active cellular forces. Understanding how such forces are mechanically converted into cell shape changes is essential to our understanding of morphogenesis. Here, we use myosin II pulsatile activity during Drosophila embryogenesis to study how transient forces generate irreversible cell shape changes. Analyzing the dynamics of junction shortening and elongation resulting from myosin II pulses, we find that long pulses yield less reversible deformations, typically a signature of dissipative mechanics. This is consistent with a simple viscoelastic description, which we use to model individual shortening and elongation events. The model predicts that dissipation typically occurs on the minute timescale, a timescale commensurate with that of force generation by myosin II pulses. We test this estimate by applying time-controlled forces on junctions with optical tweezers. Finally, we show that actin turnover participates in dissipation, as reducing it pharmacologically increases the reversibility of contractile events. Our results argue that active junctional deformation is stabilized by actin-dependent dissipation. Hence, tissue morphogenesis requires coordination between force generation and dissipation. PMID- 28988859 TI - How the Land Became the Locus of Major Evolutionary Innovations. AB - Life originated in the sea and evolved its early metabolic pathways in water [1, 2]. Nevertheless, activities of organisms on land have influenced and enriched marine ecosystems with oxygen and nutrients for billions of years [3-7]. In contrast to the history of species diversity in the sea and on land [8-10] and the flows of resources within and between these two realms [11], little is known about the times and places of origin of major metabolic and ecological innovations during the Phanerozoic. Many innovations among multicellular organisms originated in the sea during or before the Cambrian, including predation and most of its variations, biomineralization, colonial or clonal growth, bioerosion, deposit feeding, bioturbation by animals, communication at a distance by vision and olfaction, photosymbiosis, chemosymbiosis, suspension feeding, osmotrophy, internal fertilization, jet propulsion, undulatory locomotion, and appendages for movement. Activity is less constrained in air than in the denser, more viscous medium of water [9, 12-14]. I therefore predict that high-performance metabolic and ecological innovations should predominantly originate on land after the Ordovician once organisms had conquered the challenges of life away from water and later appeared in the sea, either in marine-colonizing clades or by arising separately in clades that never left the sea. In support of this hypothesis, I show that 11 of 13 major post-Ordovician innovations appeared first or only on land. This terrestrial locus of innovation cannot be explained by the Cretaceous to recent expansion of diversity on land. It reveals one of several irreversible shifts in the history of life. PMID- 28988858 TI - An Anatomically Constrained Model for Path Integration in the Bee Brain. AB - Path integration is a widespread navigational strategy in which directional changes and distance covered are continuously integrated on an outward journey, enabling a straight-line return to home. Bees use vision for this task-a celestial-cue-based visual compass and an optic-flow-based visual odometer-but the underlying neural integration mechanisms are unknown. Using intracellular electrophysiology, we show that polarized-light-based compass neurons and optic flow-based speed-encoding neurons converge in the central complex of the bee brain, and through block-face electron microscopy, we identify potential integrator cells. Based on plausible output targets for these cells, we propose a complete circuit for path integration and steering in the central complex, with anatomically identified neurons suggested for each processing step. The resulting model circuit is thus fully constrained biologically and provides a functional interpretation for many previously unexplained architectural features of the central complex. Moreover, we show that the receptive fields of the newly discovered speed neurons can support path integration for the holonomic motion (i.e., a ground velocity that is not precisely aligned with body orientation) typical of bee flight, a feature not captured in any previously proposed model of path integration. In a broader context, the model circuit presented provides a general mechanism for producing steering signals by comparing current and desired headings-suggesting a more basic function for central complex connectivity, from which path integration may have evolved. PMID- 28988860 TI - Theta Phase Synchronization Is the Glue that Binds Human Associative Memory. AB - Episodic memories are information-rich, often multisensory events that rely on binding different elements [1]. The elements that will constitute a memory episode are processed in specialized but distinct brain modules. The binding of these elements is most likely mediated by fast-acting long-term potentiation (LTP), which relies on the precise timing of neural activity [2]. Theta oscillations in the hippocampus orchestrate such timing as demonstrated by animal studies in vitro [3, 4] and in vivo [5, 6], suggesting a causal role of theta activity for the formation of complex memory episodes, but direct evidence from humans is missing. Here, we show that human episodic memory formation depends on phase synchrony between different sensory cortices at the theta frequency. By modulating the luminance of visual stimuli and the amplitude of auditory stimuli, we directly manipulated the degree of phase synchrony between visual and auditory cortices. Memory for sound-movie associations was significantly better when the stimuli were presented in phase compared to out of phase. This effect was specific to theta (4 Hz) and did not occur in slower (1.7 Hz) or faster (10.5 Hz) frequencies. These findings provide the first direct evidence that episodic memory formation in humans relies on a theta-specific synchronization mechanism. PMID- 28988861 TI - Centrifugal Displacement of Nuclei Reveals Multiple LINC Complex Mechanisms for Homeostatic Nuclear Positioning. AB - Nuclear movement is critical for developmental events, cell polarity, and migration and is usually mediated by linker of nucleoskeleton and cytoskeleton (LINC) complexes connecting the nucleus to cytoskeletal elements. Compared to active nuclear movement, relatively little is known about homeostatic positioning of nuclei, including whether it is an active process. To explore homeostatic nuclear positioning, we developed a method to displace nuclei in adherent cells using centrifugal force. Nuclei displaced by centrifugation rapidly recentered by mechanisms that depended on cell context. In cell monolayers with wounds oriented orthogonal to the force, nuclei were displaced toward the front and back of the cells on the two sides of the wound. Nuclei recentered from both positions, but at different rates and with different cytoskeletal linkage mechanisms. Rearward recentering was actomyosin, nesprin-2G, and SUN2 dependent, whereas forward recentering was microtubule, dynein, nesprin-2G, and SUN1 dependent. Nesprin-2G engaged actin through its N terminus and microtubules through a novel dynein interacting site near its C terminus. Both activities were necessary to maintain nuclear position in uncentrifuged cells. Thus, even when not moving, nuclei are actively maintained in position by engaging the cytoskeleton through the LINC complex. PMID- 28988863 TI - Dorsal Raphe Serotonergic Neurons Control Intertemporal Choice under Trade-off. AB - Appropriate choice about delayed reward is fundamental to the survival of animals. Although animals tend to prefer immediate reward, delaying gratification is often advantageous. The dorsal raphe (DR) serotonergic neurons have long been implicated in the processing of delayed reward, but it has been unclear whether or when their activity causally directs choice. Here, we transiently augmented or reduced the activity of DR serotonergic neurons, while mice decided between differently delayed rewards as they performed a novel odor-guided intertemporal choice task. We found that these manipulations, precisely targeted at the decision point, were sufficient to bidirectionally influence impulsive choice. The manipulation specifically affected choices with more difficult trade-off. Similar effects were observed when we manipulated the serotonergic projections to the nucleus accumbens (NAc). We propose that DR serotonergic neurons preempt reward delays at the decision point and play a critical role in suppressing impulsive choice by regulating decision trade-off. PMID- 28988862 TI - Early Pheromone Experience Modifies a Synaptic Activity to Influence Adult Pheromone Responses of C. elegans. AB - Experiences during early development can influence neuronal functions and modulate adult behaviors [1, 2]. However, the molecular mechanisms underlying the long-term behavioral effects of these early experiences are not fully understood. The C. elegans ascr#3 (asc-DeltaC9; C9) pheromone triggers avoidance behavior in adult hermaphrodites [3-7]. Here, we show that hermaphrodites that are briefly exposed to ascr#3 immediately after birth exhibit increased ascr#3-specific avoidance as adults, indicating that ascr#3-experienced animals form a long lasting memory or imprint of this early ascr#3 exposure [8]. ascr#3 imprinting is mediated by increased synaptic activity between the ascr#3-sensing ADL neurons and their post-synaptic SMB motor neuron partners via increased expression of the odr-2 glycosylated phosphatidylinositol (GPI)-linked signaling gene in the SMB neurons. Our study suggests that the memory for early ascr#3 experience is imprinted via alteration of activity of a single synaptic connection, which in turn shapes experience-dependent plasticity in adult ascr#3 responses. PMID- 28988864 TI - Museum Genomics Confirms that the Lord Howe Island Stick Insect Survived Extinction. AB - The Lord Howe Island stick insect, Dryococelus australis, was once common on the island but was driven to extinction after the arrival of ship rats in the early 20th century [1, 2]. It was thought to be extinct for decades, until a tiny population of similar-looking stick insects was discovered 20 km away, on the islet of Ball's Pyramid, in 2001 [2]. Individuals from this population are currently being reared in Australia and elsewhere in the world, with the eventual goal of recolonizing Lord Howe Island [3]. Recent surveys of the wild population on Ball's Pyramid suggest that it is among the world's rarest species. However, there are significant morphological differences between Ball's Pyramid and museum specimens, and there has never been a genetic confirmation of the rediscovered population's species identity. Because Dryococelus is monotypic, there are also no known extant relatives for comparison. Using shotgun genomic data from the Ball's Pyramid population, we assembled a draft genome and the complete mitochondrial genome. We found that the genome is massive, over 4 Gb in size, and is most likely hexaploid. We re-sequenced mitochondrial genomes from historic museum specimens collected on Lord Howe Island before the extinction event. Sequence divergence between the two populations is less than 1% and is within the range of intraspecific differences between the museum specimens, suggesting that they are conspecific and that D. australis has successfully evaded extinction so far. This work highlights the importance of museum collections for taxonomic validation in the context of ongoing conservation efforts. PMID- 28988865 TI - Impact of Haemophilus influenzae type b conjugate vaccination on hospitalization for invasive disease in children fifteen years after its introduction in Italy. AB - In Italy, Hib conjugate vaccine was introduced for infants in 1999 and included in the DTaP-HBV-IPV-Hib combination in 2001, with an uptake of 83.4% in 2002, >90% by 2005, and >95% by 2011. We estimated the impact of Hib vaccination on hospitalizations for H. influenzae invasive disease in children <5years. Age specific hospitalization rates and hospitalization risk ratios (HRRs) with 95%CI during 2001-2013 were calculated performing time-series analysis. The number of cases reported to the national surveillance of invasive bacterial diseases was compared to the number of hospitalizations between 2007-2013. Hospitalization rates declined from 2.3 in 2001 to 0.9*100,000 in 2002 (HRR=0.4, 95%CI=0.3-0.6, p<0.05) among children 1-4years and from 5.4 in 2001 to 2.4*100,000 in 2005 (HRR=0.4, 95%CI=0.2-0.9, p<0.05) among infants. During 2007-2013: 401 cases were reported, 242 were typed, 12.4% were by serotype b; 861 hospital admissions were recorded. Applying the percentage of typed b strains retrieved from the surveillance to the number of hospitalizations for invasive H. influenzae disease, an estimated 107 episodes could be attributable to serotype b. These findings provided reassuring data on the impact of Hib vaccination on the burden of hospitalization for invasive disease in Italian children. PMID- 28988866 TI - Changing livestock vaccination policy alters the epidemiology of human anthrax, Georgia, 2000-2013. AB - Anthrax is a widely spread zoonotic disease found on nearly every continent. To control the disease in humans and animals, annual livestock vaccination is recommended. However, in 2007, the country of Georgia ended its policy of compulsory annual livestock anthrax vaccination. Our objective was to assess how the epidemiology of human anthrax has evolved from 2000-2013 in Georgia, in the wake of this cessation. We used passive surveillance data on epidemiological surveys of human anthrax case patients. Risk factors and rates of self-reported sources of infection were compared, before and after the change in livestock vaccination policy. We mapped ethnicity-adjusted incidence during the two periods and assessed changes in the spatial pattern of risk. The overall risk of human anthrax increased >5-fold, from 0.7 cases per 100,000 in 2000 to 3.7 cases per 100,000 by 2013. Ethnic disparities in risk became pronounced; from 2000 to 2013, incidence increased >60-fold in Azerbaijanis from 0.35 to 21.1 cases/100,000 Azerbaijanis compared to 0.61 to 1.9 cases/100,000 among ethnic Georgians. Food borne exposures from purchasing meat increased from 11% in 2000-2006 to 21% in 2007-2013. Spatial analyses revealed a shift from a random pattern of reporting pre-policy change to clustering among district municipalities following the change in policy. Our findings indicate there were unintended human health consequences associated with changing livestock vaccination policy. Following a reduction in the immunizations administered, there was a major shift in the epidemiology of human anthrax in Georgia. Current infection risk is now highest among ethnic minorities. Increased reporting among individuals uncharacteristically at risk for anthrax from foodborne exposures suggests spillover from modes of agricultural production. Given the importance of human livestock health linkages, careful evaluations of policy need to be undertaken before changes to animal vaccination are made. PMID- 28988867 TI - Hepatitis B vaccine and the need for a booster dose after primary vaccination. AB - OBJECTIVES: Protective antibodies levels, induced by Hepatitis B virus (HBV) vaccine, persist for long-term after primary immunization, but there is evidence that, as the time since vaccination increases, there is a reduced ability to maintain immune memory. The study aim was to determine the prevalence and the duration of persistence of an anti-HBs titer with >=10mIU/mL and eventual predictors of reduced seroprotection. METHODS: The study was conducted among students attending medical and healthcare professions schools from January 2014 to June 2016. Data were collected through the review of medical records completed during the medical surveillance visit. All subjects had received HBV vaccine according to the Italian Ministry of Health indications. RESULTS: The results are reported for 722 subjects. Positive anti-HBs titer was found in 72.6% (95% CI=69 76). The mean age of the subjects was 25.5years. Subjects vaccinated during adolescence and students that had received an adult vaccine dose were significantly more likely to be seroprotected. The longer the time interval since vaccination the lower the probability of being seroprotected; however if the role of time since vaccination was considered after stratification by vaccine dose, a statistically significant association with a lower percentage of seroprotected remains only in the subgroup of subjects who received the pediatric dose. The findings of the multivariate regression analysis partially confirmed those of the univariate analysis. CONCLUSIONS: In conclusion, our findings show that over 25% of HBV vaccine recipients had an antiHBs titer <10mIU/ml after 18years of more from the primary vaccination. Furthermore, in the case a booster dose would be needed, our results suggest that the vaccination strategy should prefer administration of a vaccine adult dose during early adolescence, since it might offer longer-term protection through adulthood. PMID- 28988868 TI - Characterization of the DNA mismatch repair proteins MutS and MutL in a hypermutator Acinetobacter baumannii. AB - Mutations of mutS and mutL genes have been linked with the emergence of hypermutator (HPM) phenotype in several bacteria. Nevertheless, there is scarce evidence that these mutations occurred in HPM Acinetobacter baumannii, therefore, it remains unknown whether the mutations located in domains mediating the functions of MutS and MutL. To address this information gap, the nucleotide sequences of mutS and mutL were characterized and their mutations were identified. Additionally, we proposed in silico models of mutated proteins and analyzed the secondary and tertiary structures, and the interaction interfaces of MutL and MutS. The HPM A. baumannii and a wild-type strain were subjected to PCR amplification of full length mutS and mutL, cloning, and sequencing. Following several reads of both strands of each gene and sequence assembly, the mutations were identified. Thereafter, the three-dimensional (3-D) structure of A. baumannii ATCC 19606 was developed and utilized as a template for homology modeling of the mutated amino acid sequences using the Phyre2 and I-TASSER, VMD 1.9.3, LigPlus v.1.4.5, PyMOL v.0.99 software. Regardless of silent mutations (n = 43), 11 missense mutations were identified in the MutS domains of HPM strain such as A4T, T272S, D278N in N-terminus, connector, and core domains, respectively. Three mutations -I357T, A408S, N447S- and 16 silent mutations were observed in MutL. Secondary structure prediction of MutS revealed that the amount of alpha helices, beta sheets, and coils in HPM were 35, 29, and 63, respectively, while these values were 36, 28, and 63 for A. baumannii ATCC 19606 as non mutator. In the case of MutL, for both HPM and non-mutator, 20, 21, and 39 of complete protein were alpha helices, beta sheets, and coils, respectively. Superimposition of structures of MutS of HPM on non-mutator revealed that T272, D278, G457, S528, A533, Y715, and E747 are closely matched with S272, D278, A457, P528, V533, C715, and K747, respectively in non-mutator strain. When the structure of MutL model in HPM was superimposed on its counterpart in non mutator, all but residues S447, S408, and T357 were identical. Many mutations along the mutS and mutL were noted, but most of the mutations were observed in the interaction interfaces of MutS and MutL. Other substitutions were predominantly detected in C-terminus of MutS that may lead to reduced ATP binding and hydrolysis. Three substitution mutations were adjacent to C-terminus of MutL and are raising the suggestion of reduction in MutL dimerization. It seems that a combination of these mutations is implicated in increased mutation frequency and accordingly emergence of HPM strain. PMID- 28988869 TI - Multiple-locus variable-number tandem-repeat analysis in Salmonella isolates as an effective molecular subtyping method. AB - Due to the limitations of serotyping, to differentiate closely related microbial isolates and to investigate disease outbreaks, molecular genotyping methods including multiple loci variable number of tandem repeats (VNTR) analysis (MLVA) has been developed. The usefulness of MLVA was recently demonstrated for Salmonella Infantis and Salmonella Enteritidis isolated from human sources in Iran. In the present study. The discriminatory ability of this method was investigated in 78 Iranian Salmonella enterica isolates. Salmonella strains isolated from human urine, stool, bone marrow, blood, ascites and synovial fluid sources in Iran during the years 2012 and 2015 were analyzed. Among these 78 Salmonella isolates, 70 isolates belonging to eight serotypes/serogroups, while eight were nontypeable. Six VNTR loci were amplified from all isolates. The isolates were distributed into 67 genotypes. Two out of the 6 markers (Sal20 and Sal16) were highly discriminatory for all strains (DI > 0.80) while composition of all VNTR loci produced 67 different types with 0.995 D value. The high discrimination power of MLVA in Salmonella molecular typing via combination of VNTR loci studied here, suggesting that this method is highly valuable for molecular epidemiology of Salmonella strains. PMID- 28988870 TI - Pulmonary exposure to metal fume particulate matter cause sleep disturbances in shipyard welders. AB - Sleep disorders may pose a risk to workers in the workplace. We aimed to investigate the associations between metal fume fine particulate matter (PM2.5) and sleep quality in workers. We assessed the effects of personal exposure to metal fume PM2.5 on lung functions, urinary biomarkers, and sleep quality in shipyard welding workers. In total, 96 welding workers and 54 office workers were recruited in the present study; office workers were exposed to 82.1 +/- 94.1 MUg/m3 PM2.5 and welding workers were exposed to 2166.5 +/- 3149.1 MUg/m3. Welding workers had significantly lower levels of FEV25-75 than office workers (p < 0.05). An increase in 1 MUg/m3 PM2.5 was associated with a decrease of 0.003 ng/mL in urinary serotonin (95% CI = -0.007-0.000, p < 0.05) in all workers and with a decrease of 0.001 ng/mL in serotonin (95% CI = -0.004-0.002, p < 0.05) in welding workers, but these were not observed in office workers. There was no significant association of PM2.5 with urinary cortisol observed in any workers. Urinary serotonin was associated with urinary Cu, Mn, Co, Ni, Cd, and Pb. Urinary cortisol was associated with Cu, Mn, Co, Ni, Cd, and Pb. Sixteen subjects were randomly selected from each of the office and welding workers for personal monitoring of sleep quality using a wearable device. We observed that welding workers had greater awake times than did office workers (p < 0.05). Our study observed that exposure to heavy metals in metal fume PM2.5 may disrupt sleep quality in welding workers. PMID- 28988871 TI - Adsorption and desorption of phthalic acid esters on graphene oxide and reduced graphene oxide as affected by humic acid. AB - The implications of humic acid (HA) regarding surface properties of graphene materials and their interactions with phthalic acid esters (PAEs) are not vivid. We report the role of HA on graphene oxide (GO) and reduced graphene oxide (RGO) for sorption-desorption behavior of PAEs. Besides higher surface area and pore volume, the hydrophobic pi-conjugated carbon atoms on RGO ensured prominent adsorption capacity towards PAEs in comparison to hydrophilic GO, highlighting the hydrophobic effect. After adjusting for the hydrophobic effect by calculating the hexadecane-water partition coefficient (KHW) normalized adsorption coefficient (Kd/KHW), the dimethyl phthalate (DMP) molecule portrayed a higher adsorption affinity towards RGO by pi-pi electron donor-acceptor (EDA) interaction for active sites on graphene interface via sieving effect. In contrast to RGO, the weak pi-pi EDA interactions and H-bonding was observed between the carbonyl groups of PAEs and oxygen containing functional groups on GO. There was no obvious change in morphologies of GO and RGO before and desorption as revealed by SEM and TEM images, as desorption hysteresis did not occur in all conditions. The presence of HA also resulted in shielding effect thereby decreasing the adsorption rate and capacity of diethyl phthalate (DEP) on GO and RGO, while it had little effect on DMP, probably due to the adsorbed HA as new active sites. The desorption of DMP and DEP on RGO in presence of HA was quick and enhanced. These results should be important for evaluating the fate and health risk of graphene materials and PAEs in the environment. PMID- 28988872 TI - Photocatalysis of bisphenol A by an easy-settling titania/titanate composite: Effects of water chemistry factors, degradation pathway and theoretical calculation. AB - Bisphenol A (BPA) is a widely concerned endocrine disrupting chemical and hard to be removed through conventional wastewater treatment processes. In this study, we developed a TiO2 decorated titanate nanotubes composite (TiO2/TNTs) and used for photocatalytic degradation of BPA. TEM and XRD analysis show that the TiO2/TNTs is a nano-composite of anatase and titanate, with anatase acting as the primary photocatalytic site and titanate as the skeleton. TiO2/TNTs exhibited excellent photocatalytic reactivity and its easy-settling property leaded to good reusability. After 5 reuse cycles, TiO2/TNTs also could photo-degrade 91.2% of BPA with a high rate constant (k1) of 0.039 min-1, which was much better than TiO2 and TNTs. Higher pH facilitated photocatalysis due to more reactive oxygen species produced and less material aggregation. The presence of NaCl and CaCl2 showed negligible effects on BPA degradation, but NaHCO3 caused an inhibition effect resulting from consumption of .OH. Humic acid inhibited degradation mainly due to blockage of the active sites of TiO2/TNTs. Degradation pathway was well interpreted through theoretical calculation. Hydroxyl radical played the dominate role in BPA photodegradation, and the atoms of BPA with high Fukui index based on density-functional theory (DFT) calculation are the radical easy-attacking (f0) sites. Considering the good photocatalytic reactivity, reusability, stability and settle property, TiO2/TNTs promises to be an efficient alternative for removal of organic compounds from wastewaters. PMID- 28988873 TI - Ceramides - Lipotoxic Inducers of Metabolic Disorders: (Trends in Endocrinology and Metabolism 26, 538-550; 2015). PMID- 28988874 TI - Regulation of Mammalian 13-Subunit Cytochrome c Oxidase and Binding of other Proteins: Role of NDUFA4. AB - Cytochrome c oxidase (CcO) is the final oxygen accepting enzyme complex (complex IV) of the mitochondrial respiratory chain. In contrast to the other complexes (I, II, and III), CcO is highly regulated via isoforms for six of its ten nuclear coded subunits, which are differentially expressed in species, tissues, developmental stages, and cellular oxygen concentrations. Recent publications have claimed that NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 4 (NDUFA4), originally identified as subunit of complex I, represents a 14th subunit of CcO. Results on CcO composition in tissues from adult animals and the review of data from recent literature strongly suggest that NDUFA4 is not a 14th subunit of CcO but may represent an assembly factor for CcO or supercomplexes (respirasomes) in mitochondria of growing cells and cancer tissues. PMID- 28988875 TI - Reply to Nic Lughadha et al. PMID- 28988876 TI - Pilot Study of Screening Patients for Hepatitis C Virus Infection During Outpatient Endoscopy. PMID- 28988877 TI - Intra- and inter-observer reproducibility of shoulder laxity tests: Comparison of the drawer, modified drawer and load and shift tests. AB - BACKGROUND: Conventional tests of shoulder laxity have been shown to have poor reliability due to the difficulty in palpating the subtle movements of the shoulder joint beneath the musculature. Modified drawer test that is performed while the soft tissues surrounding the shoulder are loosened has been proposed to facilitate glenohumeral joint movement and improve reliability. We hypothesised that the modified drawer test would have an improved intra- and inter-observer reproducibility in comparison to the drawer and load and shift tests. Correlation of shoulder laxity measured by these tests with generalized joint laxity was also assessed. METHODS: Forty healthy volunteers underwent bilateral shoulder examination in the clinic using the three tests for anterior and posterior laxity assessment by a consultant shoulder surgeon and a resident. The examination was repeated three months later by the same examiners in the same cohort. Intra- and inter- observer reproducibility was calculated using Kappa values. The correlation of shoulder with generalized joint laxity was also investigated. RESULTS: The modified drawer test showed significantly improved intra-observer reproducibility compared to the drawer test, but not to the load and shift (kappa = 0.173, -0.042, and 0.009, respectively). There were no significant differences in the inter-observer reproducibility between the three tests (kappa = 0.054, 0.055, and 0.056, respectively). Moderate correlation was noted between shoulder and generalized joint laxity when modified drawer test was used (r = 0.417). CONCLUSIONS: The modified drawer test improves intra- but not inter- observer reproducibility compared to the drawer test. Shoulder laxity assessed by the modified test correlated to generalized joint laxity. The modified drawer test has an improved reproducibility and correlation to generalized joint laxity over the conventional tests. PMID- 28988880 TI - Gender proteomics II. Which proteins in sexual organs. AB - : In continuity with the review dealing with differences by gender in non-sexual organs [1], this review collects data on the proteomes of the sexual organs as involved in human reproduction, under both physiological and pathological conditions. It also collects data on the tissue structures and biological fluids typical of pregnancy, such as placenta and amniotic fluid, as well as what may be tested on preimplantation embryos during medically assisted reproduction. The review includes as well mention to all fluids and secretions connected with sex organs and/or reproduction, including sperm and milk, to exemplify two distinctive items in male and female physiology. SIGNIFICANCE: The causes of infertility are only incompletely understood; the same holds for the causes, and even the early markers, of the most frequent complications of pregnancy. To these established medical challenges, present day practice adds new issues connected with medically assisted reproduction. Omics approaches, including proteomics, are building the database for basic knowledge to possibly translate into clinical testing and eventually into medical routine in this critical branch of health care. PMID- 28988878 TI - Age variation in the minimum clinically important difference in SRS-22r after surgical treatment for adult spinal deformity - A single institution analysis in Japan. AB - BACKGROUND: The Scoliosis Research Society-22r (SRS-22r) has been shown to be reliable, valid and responsive to change in patients with adult spinal deformity (ASD) undergoing surgery. The minimum clinically important difference (MCID) quantifies a threshold value of improvement that is clinically relevant to the patient. Health-related quality of life scores depend on age. The purpose of this study was to assess MCID threshold values stratified by age for SRS-22r domains in patients with ASD undergoing surgical correction. METHODS: We identified a consecutive series of 184 Japanese ASD patients who completed the SRS-22r and Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) preoperatively and 1 year postoperatively. Effectiveness as measured on the JOABPEQ was used as the anchor to determine MCID for the Function, Pain, and Mental health domains using receiver-operating-characteristic (ROC) curve analysis. We performed MCID analysis stratified by age (<70 or >=70). RESULTS: Mean preoperative SRS-22r Function score was 2.69 improving to 3.23 at postoperatively (p < 0.001). Mean preoperative SRS-22r Pain score was 3.04 improving to 3.78 at postoperatively (p < 0.001). Mean preoperative SRS-22r Mental health score was 2.72 improving to 3.25 at postoperatively (p < 0.001). There was a statistically difference in change in domain score between "not effective" and "effective" (p < 0.001). The ROC curve analysis methods yielded MCID values of 0.58 for Function, 0.55 for Pain, and 0.70 for Mental health domains. There was difference of MCID value for Function and Mental health domain between aged <70 and >=70; 0.78 and 0.55 for Function; 0.70 and 0.48 for Mental health. CONCLUSION: Results of this study showed that MCID threshold values for SRS-22 Function and Mental health domains in older than 70 was lower than in younger than 70, potentially implying that older patients have lower expectation. PMID- 28988879 TI - Roadmap for Tuberculosis Elimination in Latin America and the Caribbean. PMID- 28988881 TI - Comprehensive proteomic profiles of mouse AApoAII amyloid fibrils provide insights into the involvement of lipoproteins in the pathology of amyloidosis. AB - : Amyloidosis is a disorder characterized by extracellular fibrillar deposits of misfolded proteins. The amyloid deposits commonly contain several non-fibrillar proteins as amyloid-associated proteins, but their roles in amyloidosis pathology are still unknown. In mouse senile amyloidosis, apolipoprotein A-II (ApoA-II) forms extracellular amyloid fibril (AApoAII) deposits with other proteins (AApoAII-associated proteins) in many organs. We previously reported that R1.P1 Apoa2c mice provide a reproducible model of AApoAII amyloidosis. In order to investigate the sequential alterations of AApoAII-associated protein, we performed a proteomic analysis of amyloid fibrils extracted from mouse liver tissues that contained different levels of AApoAII deposition. We identified 6 AApoAII-associated proteins that constituted 20 of the top-ranked proteins in mice with severe AApoAII deposition. Although the amount of AApoAII-associated proteins increased with the progression of amyloidosis, the relative abundance of AApoAII-associated proteins changed little throughout the progression of amyloidosis. On the other hand, plasma levels of these proteins showed dramatic changes during the progression of amyloidosis. In addition, we confirmed that AApoAII-associated proteins were significantly associated with lipid metabolism based on functional enrichment analysis, and lipids were co-deposited with AApoAII fibrils from early stages of development of amyloidosis. Thus, these results demonstrate that lipoproteins are involved in AApoAII amyloidosis pathology. SIGNIFICANCE: This study presented proteomic profiles of AApoAII amyloidosis during disease progression and it revealed co-deposition of lipids with AApoAII deposits based on functional analyses. The relative abundance of AApoAII-associated proteins in the amyloid fibril fractions did not change over the course of development of AApoAII amyloidosis pathology. However, their concentrations in plasma changed dramatically with progression of the disease. Interestingly, several AApoAII-associated proteins have been found as constituents of lipid-rich lesions of other degenerative diseases, such as atherosclerosis and age-related macular degeneration. The common protein components among these diseases with lipid-rich deposits could be accounted for by a lipoprotein retention model. PMID- 28988882 TI - Gender proteomics I. Which proteins in non-sexual organs. AB - : Differences related to gender have long been neglected but recent investigations show that they are widespread and may be recognized with all types of omics approaches, both in tissues and in biological fluids. Our review compiles evidence collected with proteomics techniques in our species, mainly focusing on baseline parameters in non-sexual organs in healthy men and women. Data from human specimens had to be replaced with information from other mammals every time invasive procedures of sample procurement were involved. SIGNIFICANCE: As our knowledge, and the methods to build it, get refined, gender differences need to receive more and more attention, as they influence the outcome of all aspects in lifestyle, including diet, exercise and environmental factors. In turn this background modulates a differential susceptibility to some disease, or a different pathogenetic mechanism, depending on gender, and a different response to pharmacological therapy. Preparing this review we meant to raise awareness about the gender issue. We anticipate that more and more often, in the future, separate evaluations will be carried out on male and female subjects as an alternative - and an upgrade - to the current approach of reference and test groups being 'matched for age and sex'. PMID- 28988883 TI - T1-weighted parenchyma attenuated inversion recovery: A novel sequence that improves contrast ratio of enhancing brain lesions. AB - PURPOSE: The purpose of this study was to develop and test a parenchyma attenuated T1-weighted inversion recovery MR sequence (PAIR) that increases the contrast between enhancing and non-enhancing tissues in the brain and to compare the contrast ratio of enhancing brain tumors on this sequence compared to spin echo magnetization transfer (SEMT). PATIENTS AND METHODS: PAIR sequence parameters were developed to reduce signal from gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) in a healthy adult volunteer. Forty-one patients (17 men and 24 women) with a mean age of 55+/-13 (SD) years (range: 21 78years) with known or suspected brain tumors underwent PAIR and SEMT imaging after intravenous administration of gadobenate dimeglumine. In patients with confirmed tumors, PAIR and SEMT images were compared for contrast ratio of tumor to-WM, tumor-to-GM, and tumor-to-CSF. RESULTS: A total of 23 enhancing neoplastic lesions were found in 14/41 patients. All tumors were visualized on both contrast enhanced PAIR and SEMT images. PAIR images showed a 2.5 fold increase in maximum tumor-to-GM contrast ratio (P<0.0001), a 1.4 fold increase in maximum tumor-to-WM contrast ratio (P=0.0007) and a 5-fold increase in maximum tumor-to-CSF contrast ratio (P<0.0001). CONCLUSION: PAIR provides improved lesion-to-background contrast ratio compared to SEMT and may be useful as an added sequence in tumor evaluation. PMID- 28988884 TI - Cerebral Hyperperfusion Syndrome, an Unusual but Disastrous Complication of Carotid Recanalization: A Case Report. AB - Cerebral hyperperfusion syndrome (CHS), known as the dark side of carotid recanalization, happens in about 0%-3% of patients. Unfortunately, physicians involving in carotid recanalization generally are not aware of diagnostic and therapeutic aspects of this unusual but potentially life-threatening disorder. Severe bilateral carotid stenosis is suggested to predispose patients to CHS by decrement of cerebrovascular reactivity in a setting of chronic hypoperfusion state. We here introduced such a case; a 69-year-old man, a known case of hypertension and ischemic heart disease, who developed progressive intracranial hypertension underlying CHS after carotid stenting because of symptomatic severe bilateral carotid stenosis. PMID- 28988887 TI - IgE induces hypotension in asthma mice by down-regulating vascular NCX1 expression through activating MiR-212-5p. AB - Immunoglobulin E (IgE) has been suggested as a risk factor for allergy-induced low blood pressure, which has not been well explained in molecular details. Our current study shows a novel mechanism involving IgE, FcER1, miRNA-212-5p (miR-212 5p), and sodium/calcium exchanger protein 1(NCX1) for asthma to induce hypotension. In arterial smooth muscle cells, IgE up-regulated miR212-5p via its receptor FcER1, which resulted in down-regulation of NCX1 that is a regulating factor for blood pressure. In mice, asthma induced hypotension by interfering vasoconstrictive function; knockout of FcER1 kept the asthmatic mice from developing hypotension; knock-down of miR-212-5p in asthmatic mice resulted in a significant restoration of blood pressure. In human, asthma and IgE were positively correlated with hypotension in cohort study on NIH epidemiological data. This study suggests a novel therapeutic target (miR-212-5p) for treatment of asthma-induced hypotension. PMID- 28988888 TI - Small bowel tumors: A digestive endoscopy society of Taiwan (DEST) multicenter enteroscopy-based epidemiologic study. AB - BACKGROUND/PURPOSE: Small bowel (SB) accounts for the majority of gastrointestinal tract but its tumors are rare and always overlooked. In this study, we aimed to evaluate the epidemiology of SB tumors. METHODS: This multicenter retrospective study utilized endoscopy database from 2006/11 to 2016/07. Baseline demographic characteristics, clinical, radiologic and endoscopic findings were collected. RESULTS: Totally 103 (34 benign, 69 malignant lesions) patients with SB tumors in 1070 enteroscopic examinations were enrolled. There were male preponderance (56.3% males, 43.7% females), both in benign (52.9%, 49.1%) and malignant (58.0%, 42.0%) lesions, except for subtype gastrointestinal stromal tumors (GISTs) (31.6%, 68.4%). The age (mean +/- SD) at diagnosis in malignant SB tumors (62.2 +/- 15.6) was older than those with benign tumors (50.7 +/- 21.4) (p < 0.01). Bleeding (43.7%), abdominal pain (40.8%) and ileus (10.7%) were the most common clinical presentations. Hamartoma (32.4%) and adenoma (14.7%) were the most common benign histology. Four major malignant histological subtypes were lymphomas (29.0%), GISTs (27.5%), adenocarcinomas (26.1%) and metastatic cancers (14.5%). SB adenocarcinoma patients (>60-year-old, 77.8%) were older than lymphomas (60%) and GISTs (50%). Proximally location rates of lymphomas, GISTs, adenocarcinomas were 25.0% (5/20), 84.2% (16/19), and 88.9% (16/18), respectively. CONCLUSION: This endoscopy-based study revealed the most common histology of benign SB tumors were hamartoma and adenoma, and malignant ones were lymphomas, GISTs, adenocarcinomas and metastatic cancers. Most of them were male gender, except for GISTs, and with proximal location, except for lymphomas. Further large-scale investigation efforts are warranted to elucidate the epidemiology of SB tumors. PMID- 28988889 TI - Severe aortic arch calcification predicts mortality in patients undergoing peritoneal dialysis: Methodological issues. PMID- 28988886 TI - The ceramide activated protein phosphatase Sit4 impairs sphingolipid dynamics, mitochondrial function and lifespan in a yeast model of Niemann-Pick type C1. AB - The Niemann-Pick type C is a rare neurodegenerative disease that results from loss-of-function point mutations in NPC1 or NPC2, which affect the homeostasis of sphingolipids and sterols in human cells. We have previously shown that yeast lacking Ncr1, the orthologue of human NPC1 protein, display a premature ageing phenotype and higher sensitivity to oxidative stress associated with mitochondrial dysfunctions and accumulation of long chain bases. In this study, a lipidomic analysis revealed specific changes in the levels of ceramide species in ncr1Delta cells, including decreases in dihydroceramides and increases in phytoceramides. Moreover, the activation of Sit4, a ceramide-activated protein phosphatase, increased in ncr1Delta cells. Deletion of SIT4 or CDC55, its regulatory subunit, increased the chronological lifespan and hydrogen peroxide resistance of ncr1Delta cells and suppressed its mitochondrial defects. Notably, Sch9 and Pkh1-mediated phosphorylation of Sch9 decreased significantly in ncr1Deltasit4Delta cells. These results suggest that phytoceramide accumulation and Sit4-dependent signaling mediate the mitochondrial dysfunction and shortened lifespan in the yeast model of Niemann-Pick type C1, in part through modulation of the Pkh1-Sch9 pathway. PMID- 28988890 TI - Current status and future challenge of population-based organized colorectal cancer screening: Lesson from the first decade of Taiwanese program. AB - Colorectal cancer (CRC) is the most common cancer in Taiwan, and is the third leading cause of cancer-related death. Screening has been proven the most effective way to reduce CRC mortality, and stool-based screening is currently the most popular method of screening worldwide. In 2004, Taiwanese government launched a nationwide screening program and fecal immunochemical test (FIT) is offered biennially to individuals aged 50 to 75. The results from the program have demonstrated that FIT screening could effectively reduce the mortality from CRC. Nevertheless, there were some problems needed to deal with. First, the occurrence of interval cancers, which are associated with the performance of screening tests or quality of colonoscopy, has affected the program sensitivity. Second, increasing participation in the program has increased the demand for colonoscopy and the burden on public health workers. Third, some individuals are non-compliant with FIT screening, and with the recommendation for colonoscopy after a positive FIT, which may be the result of insufficient awareness toward CRC and screening of the public. Fourth, long-lasting financial support for this program is necessary for its success. All of these problems need to be solved via collaboration between the screening organizer, screening distributor, and professional societies. PMID- 28988891 TI - Cancer Deaths due to Lack of Universal Access to Radiotherapy in the Brazilian Public Health System. AB - AIMS: Radiotherapy plays a fundamental role in the treatment of cancer. Currently, the Brazilian public health system cannot match the national radiotherapy demand and many patients requiring radiotherapy are never exposed to this treatment. This study estimated the number of preventable deaths in the public health system if access to radiotherapy was universal. MATERIALS AND METHODS: Incidence rates for the year 2016 provided by Instituto Nacional de Cancer were used in this analysis. The number of untreated patients requiring radiotherapy was obtained through the difference between the total number of patients requiring radiotherapy and the total amount of delivered radiotherapy treatments in the public health system. The number of deaths for the three most common cancers in each gender due to radiotherapy shortage was calculated. Initially, the total number of patients per cancer type was divided in stages using Brazilian epidemiological data. Subsequently, previously published tree arm diagrams were used to define the rate of patients requiring radiotherapy in each specific clinical setting. Finally, the clinical benefit of radiotherapy in overall survival was extracted from studies with level 1 evidence. RESULTS: Over 596 000 cancer cases were expected in Brazil in 2016. The public health system covers more than 75% of the Brazilian population and an estimated 111 432 patients who required radiotherapy in 2016 did not receive this treatment. Breast, colorectal and cervix cancers are the most frequent malignant tumours in women and prostate, lung and colorectal in men. The number of deaths due to a radiotherapy shortage in the year 2016 for these types of cancer were: (i) breast: 1011 deaths in 10 years; (ii) cervix: 2006 deaths in 2 years; (iii) lung: 1206 deaths in 2 years; (iv) prostate, intermediate risk: 562 deaths in 13 years; high risk: 298 deaths in 10 years; (v) colorectal: 0 deaths, as radiotherapy has no proven benefit in overall survival. CONCLUSION: Thousands of cancer patients requiring radiotherapy do not have access to this treatment in the Brazilian public health system. The shortage of radiotherapy has a significant detrimental effect on cancer survival; over 5000 deaths would probably be prevented in the most common cancer types if radiotherapy access was universal. PMID- 28988892 TI - The IL-1beta signalling pathway and its role in regulating pro-inflammatory and pro-labour mediators in human primary myometrial cells. AB - Interleukin (IL)-1beta plays a central role in the processes of human labour and delivery. The adaptor proteins involved in the IL-1beta signalling pathway in human myometrium are not known. This study sought to determine the role of the adaptor proteins myeloid differentiation primary response 88 (MyD88), tumour necrosis factor receptor-associated factor 6 (TRAF6), IL-1 receptor-associated kinase 4 (IRAK4) and transforming growth factor beta-activated kinase 1 (TAK1) in IL-1beta-induced formation of pro-inflammatory and pro-labour mediators in human myometrium. Human primary myometrial cells were transfected with siRNA against MyD88 (siMYD88), TRAF6 (siTRAF6), IRAK4 (siIRAK4) or TAK1 (siTAK1), treated with IL-1beta, and assayed for the mRNA expression and or secretion of pro inflammatory and pro-labour mediators. Transfection of primary myometrial cells with siMYD88, siTRAF6, siIRAK4 and siTAK1 significantly decreased IL-1beta induced IL-1alpha, IL-6, growth-regulated alpha protein (GRO-alpha), IL-8, monocyte chemoattractant protein (MCP)-1, intercellular adhesion molecule (ICAM) 1 and cyclooxygenase (COX)-2 mRNA expression and release of IL-6, GRO-alpha, IL 8, MCP-1, ICAM-1 and prostaglandin PGF2alpha. The expression and secretion of the extracellular matrix remodelling enzyme matrix metalloproteinase (MMP)-9 was significantly lower with siMYD88 and siTRAF6. Finally, IL-1beta-induced nuclear factor kappaB (NF-kappaB) transcriptional activity was significantly attenuated by transfection with siMyD88, siTRAF6 and siIRAK4; there was no effect of siTAK1 transfection on NF-kappaB transcriptional activity. Collectively, these findings suggest that MyD88, TRAF6, IRAK4 and TAK1 are involved in IL-1beta signalling in human myometrium. Further studies are required to determine if inhibition of these proteins can prevent preterm birth. PMID- 28988893 TI - Radiation therapy of synchronous bilateral breast carcinoma (SBBC) using multiple techniques. AB - The purpose of this study was to establish intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) treatment plans for synchronous bilateral breast cancer (SBBC) and to compare those plans with the previous treatment plans using 3D conformal radiation therapy (3DCRT). The differences among the treatments were also statistically compared regarding dosimetry distribution and treatment efficiency. The research was conducted with 10 SBBC patients. The study established IMRT (12 fields with a single isocenter) and VMAT (2 partial arcs with a single isocenter) treatment plans for SBBC patients and then compared those plans with 3DCRT (8 fields with multiple isocenters). The plans were evaluated based on a dose-volume histogram analysis. For planning target volumes (PTVs), the mean doses and the values of V95%, V105%, conformity index, and homogeneity index were reported. For the organs at risk, the analysis included the mean dose, maximum dose, and VXGy, depending on the organs (lungs, heart, and liver). To objectively evaluate the efficiency of the treatment plans, each plan's beam times, treatment times (including set-up time), and monitor units were compared. Tukey test and one-way analysis of variance were used to compare the PTV and organs at risk values of the 3 techniques. Additionally, the independent-samples t-test was used to compare the 2 techniques (IMRT and VMAT) based on the values of Rt. PTV and Lt. PTV (p < 0.05). For PTV dose distribution, IMRT showed increases of approximately 1.2% in Dmean and of approximately 5.7% in V95% dose distribution compared with 3DCRT. In comparison to VMAT, 3DCRT showed about 3.0% higher dose distribution in Dmean and V95%. IMRT was the best in terms of conformity index and homogeneity index (p < 0.05), whereas 3DCRT and VMAT did not significantly differ from each other. In terms of dose distribution on lungs, heart, and liver, the percentage of volume at high doses such as V30Gy and V40Gy was approximately 70% lower for IMRT and approximately 40% lower for VMAT than for 3DCRT. For distribution volumes of low doses such as V5% and V10%, that for 3DCRT was approximately 60% smaller than for IMRT and approximately 70% smaller than for VMAT. Comparison between IMRT and VMAT showed that the IMRT was superior in all distribution factors. VMAT showed better treatment efficiency than 3DCRT or IMRT. Among the SBBC radiotherapy treatment plans, IMRT was superior to 3DCRT and VMAT in terms of PTV dose distribution, whereas VMAT showed the most outstanding treatment efficiency. PMID- 28988894 TI - A novel method to construct an air quality index based on air pollution profiles. AB - BACKGROUND: Air quality indices based on the maximum of sub-indices of pollutants are easy to produce and help quantify the degree of air pollution. However, they discount the additive effects of multiple pollutants and are only sensitive to changes in highest sub-index. OBJECTIVES: We propose a simple and concise method to construct an air quality index that takes into account additive effects of multiple pollutants and evaluate the extent to which this index predicts health effects. MATERIALS AND METHODS: We obtained concentrations of four criteria pollutants: particulate matter with aerodynamic diameter <= 10MUm (PM10), sulphur dioxide (SO2), nitrogen dioxide (NO2) and ozone (O3) and daily admissions to Hong Kong hospitals for cardiovascular and respiratory diseases for all ages and those 65 years or older for years 2001-2012. We derived sub-indices of the four criteria pollutants, calculated by normalizing pollutant concentrations to their respective short-term WHO Air Quality Guidelines (WHO AQG). We aggregated the sub indices using the root-mean-power function with an optimal power to form an overall air quality index. The optimal power was determined by minimizing the sum of over- and under-estimated days. We then assessed associations between the pollution bands of the index and cardiovascular and respiratory admissions using a time-stratified case-crossover design adjusted for ambient temperature, relative humidity and influenza epidemics. Further, we conducted case-crossover analyses using the Hong Kong air quality data with the respective standards and classification of pollution bands of the China Air Quality Index (AQI), the United Kingdom Daily AQI (DAQI), and the United States Environmental Protection Agency (USEPA) AQI. RESULTS: The mean concentrations of PM10 and SO2 based on maximum 3-h mean exceeded the WHO AQG by 37% and 50%, respectively. We identified the combined condition of observed high-pollution days as either at least one pollutant > 1.5*WHO AQG or at least two pollutants > 1.0*WHO AQG to characterize the typical pollution profiles over the study period, which resulted in the optimal power=3.0. The distribution of days in different pollution bands of the index was: 5.8% for "Low" (0-50), 37.6% for "Moderate" (51-100), 31.1% for "High" (101-150), 14.7% for "Very High" (151-200), and 10.8% for "Serious" (201+). For cardiovascular and respiratory admissions, there were significant associations with the pollution bands of the index for all ages and those 65 years or older. The trends of increasing pollution bands in relation to increasing excess risks of cardiovascular and respiratory admissions were significant for the proposed index, the China AQI, the UK DAQI and the USEPA AQI (P value for test for linear trend < 0.0001), suggesting a dose-response relation. CONCLUSIONS: We have developed a simple and concise method to construct an air quality index that accounts for multiple pollutants to quantify air quality conditions for Hong Kong. Further developments are needed in order to support the extension of the method to other settings. PMID- 28988895 TI - The dynamics of the emergency medical readmission - The underlying fundamentals. AB - BACKGROUND: Hospital readmissions are a perennial problem. We reviewed readmissions to one institution (2002-2015) and investigated their dynamics. METHODS: 96,474 emergency admissions (in 50,701 patients) to an Irish hospital over a 15-year period were studied, and patterns surrounding early (<28days) and late (any other) readmissions determined. Univariate and logistic or truncated Poisson regression methods were employed. RESULTS: Early readmission rate averaged 9.6% (95% CI: 9.4, 9.8) with a low/high of 8.4% (95% CI: 7.8, 9.1) and 10.3% (95% CI: 9.6, 11.0) respectively with no overall time trend. Early readmissions represented 20.1% (95% CI: 19.8, 20.5) of emergency medical readmissions. Median time to first readmission was 55weeks (95% CI: 13, 159), time to second was 35weeks (95% CI: 9, 98); by the 7th/8th readmissions, intervals were 13weeks (95% CI: 4, 36) and 11weeks (95% CI: 4, 30). Readmissions were older 67.1years (95% CI: 48.3, 79.2) vs. single admissions 53.9years (34.3, 72.4) and stayed longer - 5.8days (2.7, 10.6) vs. 3.9days (1.5, 8.0). Readmissions had more Acute Illness Severity, Charlson Co-Morbidity and Chronic Disabling Disease. Between 2002 and 2015 the logistic adjusted model of 30-day in hospital mortality reduced from 6.1% (95% CI: 5.7, 6.5) to 4.4% (95% CI: 4.1, 4.7) (RRR 30.4%). CONCLUSION: Early hospital readmission rate did not change over 15years despite improvements in hospital mortality outcomes. Readmissions have a consistent pattern related to patient illness and social characteristics; the fundamentals are driven by disease progression over time. PMID- 28988896 TI - First laboratory confirmation on the existence of Zika virus disease in India. PMID- 28988897 TI - Outcomes and Prognostic Factors of Cataract Surgery in Adult Extreme Microphthalmos With Axial Length <18 mm or Corneal Diameter <8 mm. AB - PURPOSE: To study the long-term visual outcomes, complications, and prognostic factors for cataract surgery in extreme microphthalmos. DESIGN: Prospective cohort study. METHODS: Thirty eyes with simple microphthalmos (11 eyes, axial length [AL] <18 mm), complex microphthalmos (8 eyes, AL <18 mm), and relative anterior microphthalmos (RAM; 11 eyes, corneal diameter [CD] <8 mm) who underwent cataract surgery (phacoemulsification) in our hospital were followed for a mean of 25.3 months with at least 3 visits at early (1 day to 1 week), mid (1-3 months), and late (>6 months) stages after surgery. The main outcome measures included the best-corrected visual acuity (BCVA), intraocular pressure (IOP), and complications. RESULTS: Significant improvements of BCVA were observed at the mid and late postoperative visits in the entire cohort when compared with preoperative value (P < .05). When eyes were divided into 3 groups, a statistically significant improvement in late-stage BCVA was observed in the simple microphthalmos and RAM groups. The AL, preoperative anterior chamber depth (ACD), and preoperative BCVA were significant prognostic factors for late-stage BCVA after surgery. The most common complications were early corneal edema (73%), glaucoma (33%), and posterior capsular opacification (23%). Preoperative ACD was significantly associated with the incidence of glaucoma after surgery (P < .05). Severe complications included suprachoroidal hemorrhage (3%), endothelial dysfunction (7%), and retinal detachment (7%). CONCLUSIONS: Cataract surgery provided visual improvement in extreme microphthalmos (simple microphthalmos and RAM), with higher risks of complications than with routine cataract surgeries. Extreme microphthalmos with preoperative characteristics of relatively longer AL, deeper ACD, and better BCVA may benefit more from cataract surgery. PMID- 28988898 TI - Elevated Aqueous Cytokine Levels in Eyes With Ocular Surface Diseases. AB - PURPOSE: To evaluate cytokine and protein levels in the aqueous humor (AqH) of eyes with ocular surface diseases. DESIGN: Prospective consecutive case series. METHODS: This study includes 14 patients (aged 62.4 +/- 13.7 years) with chronic phase ocular surface diseases (4 with ocular cicatricial pemphigoid, 5 with chemical burns, 2 with a thermal burn, 2 with Stevens-Johnson syndrome, and 1 with exposure keratitis), 14 matched patients without ocular surface disease (controls with corneal scar), and 30 patients who underwent cataract surgery (healthy controls). AqH samples were collected at the beginning of surgery. AqH levels of cytokines (interleukin [IL]-1alpha, IL-1beta, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17A, monocyte chemotactic protein [MCP]-1, interferon [IFN] alpha, IFN-gamma, macrophage inflammatory protein [MIP]-1alpha, MIP-1beta, P selectin, E-selectin, soluble-intercellular adhesion molecule [s-ICAM]-1, tumor necrosis factor [TNF]-alpha, granulocyte-macrophage colony-stimulating factor [GM CSF], IFN-gamma-induced protein [IP]-10) were measured using multiplex beads immunoassays. RESULTS: The levels of IL-6, IL-10, IL-17A, GM-CSF, E-selectin, P selectin, and s-ICAM in AqH were significantly elevated in eyes with ocular surface diseases (in pg/mL: 1696 +/- 804, 4.0 +/- 1.0, 24.3 +/- 9.8, 26.0 +/- 18.3, 5150 +/- 1232, 13122 +/- 7219, and 7914 +/- 2813, respectively), compared to healthy controls (IL-6: 6.36 +/- 0.94, P = .001; IL-10: 1.68 +/- 0.04, P = .0006; IL-17A: 3.7 +/- 0.2, P = .008; GM-CSF: 2.7 +/- 0.3, P = .007; E-selectin: 2093 +/- 37, P = .0001; P-selectin: 3658 +/- 137, P = .0001; sICAM-1: 1397 +/- 119, P = .008). The levels of IL-6, IL-17A, E-selectin, and P-selectin in AqH were significantly higher in eyes with ocular surface diseases compared to those with corneal scar (IL-6: 44.1 +/- 15.0, P = .0077; IL-17A: 4.1 +/- 0.7, P = .034; E-selectin: 2439 +/- 302, P = .039; and P-selectin: 5673 +/- 1553, P = .017). CONCLUSIONS: Multiple AqH cytokine levels were elevated in chronic ocular surface diseases. PMID- 28988899 TI - Diabetic Choroidopathy: Choroidal Vascular Density and Volume in Diabetic Retinopathy With Swept-Source Optical Coherence Tomography. AB - PURPOSE: To compare choroidal vascular density (CVD) and volume (CVV) in diabetic eyes and controls, using en face swept-source optical coherence tomography (SS OCT). DESIGN: Prospective cross-sectional study. METHODS: Setting: Multicenter. PATIENT POPULATION: Total of 143 diabetic eyes-27 with no diabetic retinopathy (DR), 47 with nonproliferative DR (NPDR), 51 with NPDR and diabetic macular edema (DME), and 18 with proliferative DR (PDR)-and 64 age-matched nondiabetic control eyes. OBSERVATION PROCEDURES: Complete ophthalmologic examination and SS-OCT imaging. En face SS-OCT images of the choroidal vasculature were binarized. MAIN OUTCOME MEASURES: CVD, calculated as the percent area occupied by choroidal vessels in the central macular region (6-mm-diameter circle centered on the fovea), and throughout the posterior pole (12 * 9 mm). The central macular CVV was calculated by multiplying the average CVD by macular area and choroidal thickness (obtained with SS-OCT automated software). Multilevel mixed linear models were performed for analyses. RESULTS: Compared to controls (0.31 +/- 0.07), central macular CVD was significantly decreased by 9% in eyes with NPDR + DME (0.28 +/- 0.06; beta = -0.03, P = .02) and by 15% in PDR (0.26 +/- 0.05; beta = -0.04, P = .01). The central macular CVV was significantly decreased by 19% in eyes with PDR (0.020 +/- 0.005 mm3, beta = -0.01, P = .01) compared to controls (0.025 +/- 0.01 mm3). CONCLUSIONS: Choroidal vascular density and volume are significantly reduced in more advanced stages of diabetic retinopathy. New imaging modalities should allow further exploration of the contributions of choroidal vessel disease to diabetic eye disease pathogenesis, prognosis, and treatment response. PMID- 28988900 TI - Biofilm-forming capacity of blood-borne Candida albicans strains and effects of antifungal agents. AB - Infections related to Candida albicans biofilms and subsequent antifungal resistance have become more common with the increased use of indwelling medical devices. Regimens for preventing fungal biofilm formation are needed, particularly in high-risk patients. In this study, we investigated the biofilm formation rate of multiple strains of Candida albicans (n=162 clinical isolates), their antifungal susceptibility patterns, and the efficacy of certain antifungals for preventing biofilm formation. Biofilm formation was graded using a modified Christensen's 96-well plate method. We further analyzed 30 randomly chosen intense biofilm-forming isolates using the XTT method. Minimum biofilm inhibition concentrations (MBIC) of caspofungin, micafungin, anidulafungin, fluconazole, voriconazole, posaconazole, itraconazole, and amphotericin B were determined using the modified Calgary biofilm method. In addition, the inhibitory effects of antifungal agents on biofilm formation were investigated. Our study showed weak, moderate, and extensive biofilm formation in 29% (n=47), 38% (n=61), and 23% (n=37) of the isolates, respectively. We found that echinocandins had the lowest MBIC values and that itraconazole inhibited biofilm formation in more isolates (26/32; 81.3%) than other tested agents. In conclusion, echinocandins were most effective against formed biofilms, while itraconazole was most effective for preventing biofilm formation. Standardized methods are needed for biofilm antifungal sensitivity tests when determining the treatment and prophylaxis of C. albicans infections. PMID- 28988901 TI - Detection of toxigenic Clostridioides [Clostridium] difficile: Usefulness of two commercially available enzyme immunoassays and a PCR assay on stool samples and stool isolates. AB - The best laboratory diagnostic approach to detect Clostridioides [Clostridium] difficile infection (CDI) is a subject of ongoing debate. With the aim of evaluating four laboratory diagnostic methods, 250 unformed stools from patients with suspected CDI submitted to nine medical center laboratories from November 2010 to December 2011, were studied using: (1) an immunochromatographic rapid assay test that combines the qualitative determination of glutamate dehydrogenase (GDH) plus toxins A and B (QAB), the CDIFF QUIK CHEK COMPLETE assay; (2) an enzyme immunoassay for qualitative determination of toxins A and B, the RIDASCREENTM C. difficile Toxin A/B assay (RAB); (3) a PCR for the toxin B gene assay (PCR); and (4) the toxigenic culture (TC). C. difficile isolates from direct toxin negative stools by QAB, RAB and PCR were evaluated for toxigenicity by the same direct tests, in order to assess the contribution of the TC (QAB-TC, RAB-TC, PCR-TC). A combination of the cell culture cytotoxicity neutralization assay (CCCNA) in stools, and the same assay on isolates from direct negative samples (CCCNA-TC) was considered the reference method (CCCNA/CCCNA-TC). Of the 250 stools tested, 107 (42.8%) were positive by CCCNA/CCCNA-TC. The GDH and PCR/PCR-TC assays were the most sensitive, 91.59% and 87.62%, respectively. The QAB, RAB, QAB/QAB-TC and RAB/RAB-TC had the highest specificities, ca. 95%. A negative GDH result would rule out CDI, however, its low positive likelihood ratio (PLR) of 3.97 indicates that a positive result should always be complemented with the detection of toxins. If the RAB, QAB, and PCR assays do not detect toxins from direct feces, the toxigenic culture should be performed. In view of our results, the most accurate and reliable methods to be applied in a clinical microbiology laboratory were the QAB/QAB-TC, and RAB/RAB-TC, with PLRs >10 and negative likelihood ratios <0.30. PMID- 28988903 TI - Macrolide resistance in Mycoplasma genitalium from female sex workers in Belgium. AB - OBJECTIVES: Mycoplasma genitalium is emerging as an aetiological agent of sexually transmitted infections (STIs). Although M. genitalium is commonly treated with azithromycin, macrolide resistance associated with point mutations in the 23S rRNA gene is emerging. METHODS: In this study, the prevalence of M. genitalium and macrolide resistance in female sex workers (FSW) in Belgium was evaluated by a prospective study conducted between 2015 and 2016. Vaginal swabs were sampled from 303 FSW who underwent testing for M. genitalium along with standard STI screening. All samples positive for M. genitalium were subsequently tested for mutations associated with macrolide resistance. RESULTS: M. genitalium was detected in 10.8% of participants and macrolide resistance-associated mutations (A2058G and A2059G) were found in 6.5% of isolates. CONCLUSIONS: M. genitalium is clearly present in FSW in Belgium. In contrast to other reports, for now the occurrence of macrolide resistance appears limited in this specific target population. PMID- 28988902 TI - [Evaluation of Fusarium spp. pathogenicity in plant and murine models]. AB - The genus Fusarium is widely recognized for its phytopathogenic capacity. However, it has been reported as an opportunistic pathogen in immunocompetent and immunocompromised patients. Thus, it can be considered a microorganism of interest in pathogenicity studies on different hosts. Therefore, this work evaluated the pathogenicity of Fusarium spp. isolates from different origins in plants and animals (murine hosts). Twelve isolates of Fusarium spp. from plants, animal superficial mycoses, and human superficial and systemic mycoses were inoculated in tomato, passion fruit and carnation plants, and in immunocompetent and immunosuppressed BALB/c mice. Pathogenicity tests in plants did not show all the symptoms associated with vascular wilt in the three plant models; however, colonization and necrosis of the vascular bundles, regardless of the species and origin of the isolates, showed the infective potential of Fusarium spp. in different plant species. Moreover, the pathogenicity tests in the murine model revealed behavioral changes. It was noteworthy that only five isolates (different origin and species) caused mortality. Additionally, it was observed that all isolates infected and colonized different organs, regardless of the species and origin of the isolates or host immune status. In contrast, the superficial inoculation test showed no evidence of epidermal injury or colonization. The observed results in plant and murine models suggest the pathogenic potential of Fusarium spp. isolates in different types of hosts. However, further studies on pathogenicity are needed to confirm the multihost capacity of this genus. PMID- 28988905 TI - Deciphering deep brain stimulation for depression. PMID- 28988904 TI - Subcallosal cingulate deep brain stimulation for treatment-resistant depression: a multisite, randomised, sham-controlled trial. AB - BACKGROUND: Deep brain stimulation (DBS) of the subcallosal cingulate white matter has shown promise as an intervention for patients with chronic, unremitting depression. To test the safety and efficacy of DBS for treatment resistant depression, a prospective, randomised, sham-controlled trial was conducted. METHODS: Participants with treatment-resistant depression were implanted with a DBS system targeting bilateral subcallosal cingulate white matter and randomised to 6 months of active or sham DBS, followed by 6 months of open-label subcallosal cingulate DBS. Randomisation was computer generated with a block size of three at each site before the site started the study. The primary outcome was frequency of response (defined as a 40% or greater reduction in depression severity from baseline) averaged over months 4-6 of the double-blind phase. A futility analysis was performed when approximately half of the proposed sample received DBS implantation and completed the double-blind phase. At the conclusion of the 12-month study, a subset of patients were followed up for up to 24 months. The study is registered at ClinicalTrials.gov, number NCT00617162. FINDINGS: Before the futility analysis, 90 participants were randomly assigned to active (n=60) or sham (n=30) stimulation between April 10, 2008, and Nov 21, 2012. Both groups showed improvement, but there was no statistically significant difference in response during the double-blind, sham-controlled phase (12 [20%] patients in the stimulation group vs five [17%] patients in the control group). 28 patients experienced 40 serious adverse events; eight of these (in seven patients) were deemed to be related to the study device or surgery. INTERPRETATION: This study confirmed the safety and feasibility of subcallosal cingulate DBS as a treatment for treatment-resistant depression but did not show statistically significant antidepressant efficacy in a 6-month double-blind, sham controlled trial. Future studies are needed to investigate factors such as clinical features or electrode placement that might improve efficacy. FUNDING: Abbott (previously St Jude Medical). PMID- 28988906 TI - Fluorinated phenmetrazine "legal highs" act as substrates for high-affinity monoamine transporters of the SLC6 family. AB - A variety of new psychoactive substances (NPS) are appearing in recreational drug markets worldwide. NPS are compounds that target various receptors and transporters in the central nervous system to achieve their psychoactive effects. Chemical modifications of existing drugs can generate NPS that are not controlled by current legislation, thereby providing legal alternatives to controlled substances such as cocaine or amphetamine. Recently, 3-fluorophenmetrazine (3 FPM), a derivative of the anorectic compound phenmetrazine, appeared on the recreational drug market and adverse clinical effects have been reported. Phenmetrazine is known to elevate extracellular monoamine concentrations by an amphetamine-like mechanism. Here we tested 3-FPM and its positional isomers, 2 FPM and 4-FPM, for their abilities to interact with plasma membrane monoamine transporters for dopamine (DAT), norepinephrine (NET) and serotonin (SERT). We found that 2-, 3- and 4-FPM inhibit uptake mediated by DAT and NET in HEK293 cells with potencies comparable to cocaine (IC50 values < 2.5 MUM), but display less potent effects at SERT (IC50 values >80 MUM). Experiments directed at identifying transporter-mediated reverse transport revealed that FPM isomers induce efflux via DAT, NET and SERT in HEK293 cells, and this effect is augmented by the Na+/H+ ionophore monensin. Each FPM evoked concentration-dependent release of monoamines from rat brain synaptosomes. Hence, this study reports for the first time the mode of action for 2-, 3- and 4-FPM and identifies these NPS as monoamine releasers with marked potency at catecholamine transporters implicated in abuse and addiction. This article is part of the Special Issue entitled 'Designer Drugs and Legal Highs.' PMID- 28988907 TI - Validity of utility measures for women with pelvic organ prolapse. AB - BACKGROUND: Pelvic organ prolapse is a common condition that frequently coexists with urinary and fecal incontinence. The impact of prolapse on quality of life is typically measured through condition-specific quality-of-life instruments. Utility preference scores are a standardized generic health-related quality-of life measure that summarizes morbidity on a scale from 0 (death) to 1 (optimum health). Utility preference scores quantify disease severity and burden and are widely used in cost-effectiveness research. The validity of utility preference instruments in women with pelvic organ prolapse has not been established. OBJECTIVE: The objective of this study was to evaluate the construct validity of generic quality-of-life instruments for measuring utility scores in women with pelvic organ prolapse. Our hypothesis was that women with multiple pelvic floor disorders would have worse (lower) utility scores than women with pelvic organ prolapse only and that women with all 3 pelvic floor disorders would have the worst (lowest) utility scores. STUDY DESIGN: This was a prospective observational study of 286 women with pelvic floor disorders from a referral female pelvic medicine and reconstructive surgery practice. All women completed the following general health-related quality-of-life questionnaires: Health Utilities Index Mark 3, EuroQol, and Short Form 6D, as well as a visual analog scale. Pelvic floor symptom severity and condition-specific quality of life were measured using the Pelvic Floor Distress Inventory and Pelvic Floor Impact Questionnaire, respectively. We measured the relationship between utility scores and condition specific quality-of-life scores and compared utility scores among 4 groups of women: (1) pelvic organ prolapse only, (2) pelvic organ prolapse and stress urinary incontinence, (3) pelvic organ prolapse and urgency urinary incontinence, and (4) pelvic organ prolapse, urinary incontinence, and fecal incontinence. RESULTS: Of 286 women enrolled, 191 (67%) had pelvic organ prolapse; mean age was 59 years and 73% were Caucasian. Among women with prolapse, 30 (16%) also had stress urinary incontinence, 39 (20%) had urgency urinary incontinence, and 42 (22%) had fecal incontinence. For the Health Utilities Index Mark 3, EuroQol, and Short Form 6D, the pattern in utility scores was noted to be lowest (worst) in the prolapse + urinary incontinence + fecal incontinence group (0.73-0.76), followed by the prolapse + urgency urinary incontinence group (0.77-0.85) and utility scores were the highest (best) for the prolapse only group (0.80-0.86). Utility scores from all generic instruments except the visual analog scale were significantly correlated with the Pelvic Floor Distress Inventory and Pelvic Floor Impact Questionnaire total scores (r values -0.26 to -0.57), and prolapse, bladder, and bowel subscales (r values -0.16 to -0.50). Utility scores from all instruments except the visual analog scale were highly correlated with each other (r = 0.53-0.69, P < .0001). CONCLUSION: The Health Utilities Index Mark 3, EuroQol, and Short Form 6D, but not the visual analog scale, provide valid measurements for utility scores in women with pelvic organ prolapse and associated pelvic floor disorders and could potentially be used for cost effectiveness research. PMID- 28988908 TI - Brief latency after premature rupture of the membranes at term: correction of a propagated error. PMID- 28988909 TI - Detailed muscular structure and neural control anatomy of the levator ani muscle: a study based on female human fetuses. AB - BACKGROUND: Injury to the levator ani muscle or pelvic nerves during pregnancy and vaginal delivery is responsible for pelvic floor dysfunction. OBJECTIVE: We sought to demonstrate the presence of smooth muscular cell areas within the levator ani muscle and describe their localization and innervation. STUDY DESIGN: Five female human fetuses were studied after approval from the French Biomedicine Agency. Specimens were serially sectioned and stained by Masson trichrome and immunostained for striated and smooth muscle, as well as for somatic, adrenergic, cholinergic, and nitriergic nerve fibers. Slides were digitized for 3-dimensional reconstruction. One fetus was reserved for electron microscopy. We explored the structure and innervation of the levator ani muscle. RESULTS: Smooth muscular cell beams were connected externally to the anococcygeal raphe and the levator ani muscle and with the longitudinal anal muscle sphincter. The caudalmost part of the pubovaginal muscle was found to bulge between the rectum and the vagina. This bulging was a smooth muscular interface between the levator ani muscle and the longitudinal anal muscle sphincter. The medial (visceral) part of the levator ani muscle contained smooth muscle cells, in relation to the autonomic nerve fibers of the inferior hypogastric plexus. The lateral (parietal) part of the levator ani muscle contained striated muscle cells only and was innervated by the somatic nerve fibers of levator ani and pudendal nerves. The presence of smooth muscle cells within the medial part of the levator ani muscle was confirmed under electron microscopy in 1 fetus. CONCLUSION: We characterized the muscular structure and neural control of the levator ani muscle. The muscle consists of a medial part containing smooth muscle cells under autonomic nerve influence and a lateral part containing striated muscle cells under somatic nerve control. These findings could result in new postpartum rehabilitation techniques. PMID- 28988910 TI - Neuroprotection and neurorestoration as experimental therapeutics for Parkinson's disease. AB - Disease-modifying treatments remain an unmet medical need in Parkinson's disease (PD). Such treatments can be operationally defined as interventions that slow down the clinical evolution to advanced disease milestones. A treatment may achieve this outcome by either inhibiting primary neurodegenerative events ("neuroprotection") or boosting compensatory and regenerative mechanisms in the brain ("neurorestoration"). Here we review experimental paradigms that are currently used to assess the neuroprotective and neurorestorative potential of candidate treatments in animal models of PD. We review some key molecular mediators of neuroprotection and neurorestoration in the nigrostriatal dopamine pathway that are likely to exert beneficial effects on multiple neural systems affected in PD. We further review past and current strategies to therapeutically stimulate these mediators, and discuss the preclinical evidence that exercise training can have neuroprotective and neurorestorative effects. A future translational task will be to combine behavioral and pharmacological interventions to exploit endogenous mechanisms of neuroprotection and neurorestoration for therapeutic purposes. This type of approach is likely to provide benefit to many PD patients, despite the clinical, etiological, and genetic heterogeneity of the disease. PMID- 28988911 TI - Insulin analog linked to breast cancer risk. PMID- 28988912 TI - Maintenance rituximab in mantle-cell lymphoma. PMID- 28988913 TI - Surgical treatment strategy for hepatocellular carcinoma in patients with impaired liver function: hepatic resection or radiofrequency ablation? AB - BACKGROUND: To compare the survival impacts of radiofrequency ablation (RFA) as an initial treatment for hepatocellular carcinoma (HCC) in patients with impaired liver functional reserve compared to those of hepatic resection (HR). METHODS: In total, 104 patients with liver damage B as defined by the Liver Cancer Study Group of Japan underwent RFA (n = 33) or HR (n = 71) as an initial treatment for hepatocellular carcinoma. The overall survival (OS) and disease-free survival (DFS) rates were compared, and independent prognostic factors were identified. RESULTS: The OS tended to be better in the RFA group than in the HR group. There was no significant difference in the DFS rate between the two groups. Independent poor prognostic factors for OS were tumor size >3 cm and red blood cell transfusion, and those for DFS were aspartate aminotransferase level >35 IU/L and multiple tumors. Subgroup analyses revealed that the OS with RFA was significantly better in patients with aspartate aminotransferase >35 IU/L, serum albumin <3.5 g/dL, and 99mTc-galactosyl human serum albumin <0.85. CONCLUSIONS: RFA offers comparable results with HR and may be preferable for HCC in the particular setting of liver damage B, especially in those with poorer liver functional reserve. PMID- 28988915 TI - In Memoriam-John C. Brown, PhD, DSc, FRSC, 1938-2016: Discoverer of GIP and Motilin. PMID- 28988914 TI - DNA methylation age is not accelerated in brain or blood of subjects with schizophrenia. AB - Individuals with schizophrenia (SZ) exhibit multiple premature age-related phenotypes and die ~20years prematurely. The accelerated aging hypothesis of SZ has been advanced to explain these observations, it posits that SZ-associated factors accelerate the progressive biological changes associated with normal aging. Testing the hypothesis has been limited by the absence of robust, meaningful, and multi-tissue measures of biological age. Recently, a method was described in which DNA methylation (DNAm) levels at 353 genomic sites are used to produce "DNAm age", an estimate of biological age with advantages over existing measures. We used this method and 3 publicly-available DNAm datasets, 1 from brain and 2 from blood, to test the hypothesis. The brain dataset was composed of data from the dorsolateral prefrontal cortex of 232 non-psychiatric control (NPC) and 195 SZ subjects. Blood dataset #1 was composed of data from whole blood of 304 NPC and 332 SZ subjects, and blood dataset #2 was composed of data from whole blood of 405 NPC and 260 SZ subjects. DNAm age and chronological age correlated strongly (r=0.92-0.95, p<0.0001) in both NPC and SZ subjects in all 3 datasets. DNAm age acceleration did not differ between NPC and SZ subjects in the brain dataset (t=0.52, p=0.60), blood dataset #1 (t=1.51, p=0.13), or blood dataset #2 (t=0.93, p=0.35). Consistent with our previous findings from a smaller study of postmortem brains, our findings suggest there is no acceleration of brain or blood aging in SZ and, thus, do not support the accelerated aging hypothesis of SZ. PMID- 28988916 TI - Vedolizumab Concentrations in the Breast Milk of Nursing Mothers With Inflammatory Bowel Disease. PMID- 28988917 TI - Risks of Saccharomyces boulardii-Containing Probiotics for the Prevention of Clostridium difficile Infection in the Elderly. PMID- 28988918 TI - An Unusual Cause of Elevated Liver Enzymes. PMID- 28988919 TI - Esophageal Dilation in Eosinophilic Esophagitis: Not Just for Adults Anymore. PMID- 28988920 TI - Reply. PMID- 28988921 TI - Association Between Screen-detected Gallstone Disease and Cancer in a Cohort Study. PMID- 28988922 TI - An Unusual Cause of Dysphagia in an Elderly Woman. PMID- 28988923 TI - Use of Probiotics in Hospitalized Adults to Prevent Clostridium difficile Infection: DownGRADE the Quality of Evidence? PMID- 28988924 TI - A Bidirectional Relationship Between Symptom Reporting and Perceived Stress, But Not Disease Activity, in Inflammatory Bowel Disease: More Questions Than Answers? PMID- 28988925 TI - Gallstones and Colon Cancer: A Result of a Wrong Study Revived. PMID- 28988926 TI - Reply. PMID- 28988927 TI - In Memoriam-Konrad H. Soergel, MD, 1929-2017. PMID- 28988928 TI - Preimplantation genetic screening: results of a worldwide web-based survey. AB - Our objective was to evaluate and characterize the extent and patterns of worldwide usage of preimplantation genetic screening (PGS) among the assisted reproductive technique community. A prospective, web-based questionnaire with questions relating to practices of, and views on, PGS was directed to users and non-users of PGS. A total of 386 IVF units from 70 countries conducting 342,600 IVF cycles annually responded to the survey. A total of 77% of respondents routinely carry out PGS in their clinics for a variety of indications: advanced maternal age (27%), recurrent implantation failure (32%) and recurrent pregnancy loss (31%). Few (6%) offer PGS to all their patients. In most cycles (72%), trophectoderm biopsy is carried out and either array-comparative genomic hybridization (59%) or next-generation sequencing (16%) are used for genetic analysis. Only 30% of respondents regard PGS as clearly evidenced-based, and most (84%) believe that more randomized controlled trials are needed to support the use of PGS. Despite ongoing debate and lack of robust evidence, most respondents support the use of PGS, and believe that it may aid in transferring only euploid embryos, thereby reducing miscarriage rates and multiple pregnancies, increasing live birth rates and reducing the risk of aneuploid pregnancies and births. PMID- 28988929 TI - Corrigendum to "6-Amino-2,4,5-trimethylpyridin-3-ols: A new general synthetic route and antiangiogenic activity" [Eur. J. Med. Chem. 74 (2014) 126-139]. PMID- 28988931 TI - Theoretical approaches for dynamical ordering of biomolecular systems. AB - BACKGROUND: Living systems are characterized by the dynamic assembly and disassembly of biomolecules. The dynamical ordering mechanism of these biomolecules has been investigated both experimentally and theoretically. The main theoretical approaches include quantum mechanical (QM) calculation, all-atom (AA) modeling, and coarse-grained (CG) modeling. The selected approach depends on the size of the target system (which differs among electrons, atoms, molecules, and molecular assemblies). These hierarchal approaches can be combined with molecular dynamics (MD) simulation and/or integral equation theories for liquids, which cover all size hierarchies. SCOPE OF REVIEW: We review the framework of quantum mechanical/molecular mechanical (QM/MM) calculations, AA MD simulations, CG modeling, and integral equation theories. Applications of these methods to the dynamical ordering of biomolecular systems are also exemplified. MAJOR CONCLUSIONS: The QM/MM calculation enables the study of chemical reactions. The AA MD simulation, which omits the QM calculation, can follow longer time-scale phenomena. By reducing the number of degrees of freedom and the computational cost, CG modeling can follow much longer time-scale phenomena than AA modeling. Integral equation theories for liquids elucidate the liquid structure, for example, whether the liquid follows a radial distribution function. GENERAL SIGNIFICANCE: These theoretical approaches can analyze the dynamic behaviors of biomolecular systems. They also provide useful tools for exploring the dynamic ordering systems of biomolecules, such as self-assembly. This article is part of a Special Issue entitled "Biophysical Exploration of Dynamical Ordering of Biomolecular Systems" edited by Dr. Koichi Kato. PMID- 28988930 TI - Comparison of two methods for transformation of Plasmodium knowlesi: Direct schizont electroporation and spontaneous plasmid uptake from plasmid-loaded red blood cells. AB - Human infections from Plasmodium knowlesi present challenges to malaria control in Southeast Asia. P. knowlesi also offers a model for other human malaria species including Plasmodium vivax. P. knowlesi parasites can be cultivated in the laboratory, and their transformation is standardly performed by direct electroporation of schizont-infected red blood cells (RBCs) with plasmid DNA. Here we show that the efficiency of direct electroporation is exquisitely dependent on developmental age of the schizonts. Additionally, we show that transformation of P. knowlesi can be achieved without direct electroporation by using the parasite's ability to infect and take up DNA from plasmid-loaded RBCs. Transformation with plasmid-loaded RBCs does not require labor-intensive preparations of schizont-infected RBCs as for direct electroporation, and parasite damage from high voltage discharge is avoided. Further studies of the mechanism of spontaneous DNA uptake may suggest strategies for improved transformation and provide insights into the transport pathways of apicomplexans. PMID- 28988932 TI - 6S RNA Mimics B-Form DNA to Regulate Escherichia coli RNA Polymerase. AB - Noncoding RNAs (ncRNAs) regulate gene expression in all organisms. Bacterial 6S RNAs globally regulate transcription by binding RNA polymerase (RNAP) holoenzyme and competing with promoter DNA. Escherichia coli (Eco) 6S RNA interacts specifically with the housekeeping sigma70-holoenzyme (Esigma70) and plays a key role in the transcriptional reprogramming upon shifts between exponential and stationary phase. Inhibition is relieved upon 6S RNA-templated RNA synthesis. We report here the 3.8 A resolution structure of a complex between 6S RNA and Esigma70 determined by single-particle cryo-electron microscopy and validation of the structure using footprinting and crosslinking approaches. Duplex RNA segments have A-form C3' endo sugar puckers but widened major groove widths, giving the RNA an overall architecture that mimics B-form promoter DNA. Our results help explain the specificity of Eco 6S RNA for Esigma70 and show how an ncRNA can mimic B-form DNA to directly regulate transcription by the DNA-dependent RNAP. PMID- 28988933 TI - Cancer stemness in bone marrow micrometastases of human breast cancer. AB - BACKGROUND: Cancer cells metastasize to the bone marrow to create the premetastatic niche. Cancer stemness (expression of stem cell characteristics) is regulated by the tumor microenvironment and associated with self-renewal and poor clinical outcomes. Osteopontin induces mesenchymal stem cells in the tumor microenvironment to adopt a cancer-associated fibroblast phenotype to potentiate cancer growth and metastasis. The mechanisms by which cancer cells and tumor microenvironment regulate stemness in the bone marrow premetastatic niche is unknown. METHODS: Human breast cancer cell lines, MDA-MB-231 and MCF-7 were used in an orthotopic murine xenograft model. NOD-scid mice were implanted with 2 * 106 tumor cells in the presence and absence of human mesenchymal stem cells-green fluorescent protein cells and/or osteopontin aptamer, which blocks and inactivates extracellular osteopontin, or mutant aptamer (osteopontin mutant aptamer). In select instances, MCF-7 cells transfected to express osteopontin were coimplanted instead of MCF-7. Stemness markers (Nanog, Oct4, Sox2) in the tumor cells and cancer-associated fibroblast (alpha-smooth muscle actin, Vimentin) markers in the mesenchymal stem cells were measured in femoral bone marrow via real-time polymerase chain reaction. Cell number was determined by titrating cell number to Ct value in vitro. RESULTS: Tumor cells and mesenchymal stem cells migrate from the primary tumor site to the bone marrow. Migration of mesenchymal stem cells is osteopontin dependent. In both MDA-MB-231 and MCF-7 cell lines, levels of both cancer-associated fibroblast and stemness markers were 3 to 4 times greater under conditions wherein mesenchymal stem cells were present with osteopontin. Inactivation of extracellular osteopontin with an aptamer decreased migration of mesenchymal stem cells and expression of both cancer associated fibroblast and stemness markers. Cancer cells exhibited a significantly increased stem cell profile in the presence of cancer-associated fibroblast in the bone marrow. In the presence and absence of osteopontin, Sox2 knockdown abolished expression of both Nanog and Oct4. CONCLUSION: We conclude that osteopontin-dependent migration of cancer-associated fibroblast is required for increased cancer cell stemness in the bone marrow premetastatic niche. PMID- 28988935 TI - Bis-choline tetrathiomolybdate for Wilson's disease. PMID- 28988934 TI - Bis-choline tetrathiomolybdate in patients with Wilson's disease: an open-label, multicentre, phase 2 study. AB - BACKGROUND: Wilson's disease is a genetic disorder in which copper accumulates in the liver, brain, and other tissues. Therapies are limited by efficacy, safety concerns, and multiple daily dosing. Bis-choline tetrathiomolybdate (WTX101) is an oral first-in-class copper-protein-binding molecule that targets hepatic intracellular copper and reduces plasma non-ceruloplasmin-bound copper (NCC) by forming tripartite complexes with albumin and increasing biliary copper excretion. We aimed to assess the efficacy and safety of WTX101 in the initial or early treatment of patients with Wilson's disease. METHODS: We did this open label, phase 2 study at 11 hospitals in the USA and Europe. We enrolled patients (>=18 years) with Wilson's disease who were untreated or had received no more than 24 months of treatment with chelators or zinc, had a Leipzig score of 4 or more, and had NCC concentrations above the lower limit of the normal reference range (>=0.8 MUmol/L). Eligible patients received WTX101 monotherapy at a starting dose of 15-60 mg/day on the basis of baseline NCC concentrations for the first 4-8 weeks, with response-guided individualised dosing for the remaining weeks up to week 24. Investigators, other hospital personnel, and patients were aware of the identity of the treatment. The primary endpoint was change in baseline NCC concentrations corrected for copper in tetrathiomolybdate-copper albumin complexes (NCCcorrected) at 24 weeks, with treatment success defined as achievement or maintenance of normalised NCCcorrected (<=2.3 MUmol/L [upper limit of normal]) or achievement of at least a 25% reduction in NCCcorrected from baseline at 24 weeks. This study is registered with ClinicalTrials.gov, number NCT02273596. FINDINGS: Between Nov 24, 2014, and April 27, 2016, 28 patients were enrolled and received WTX101; 22 (79%) patients completed the study up to week 24. At 24 weeks, 20 (71%, 95% CI 51.3-86.8; p<0.0001) of 28 patients met the criteria for treatment success: 16 (57%) treated with WTX101 either achieved or maintained normalised NCCcorrected concentrations and 4 (14%) had at least a 25% reduction from baseline NCCcorrected. Mean NCCcorrected was reduced by 72% from baseline to week 24 (least squares mean difference -2.4 MUmol/L [SE 0.4], 95% CI 3.2 to -1.6; p<0.0001). No cases of paradoxical drug-related neurological worsening were recorded. Liver function was stable in all patients, although reversible increased concentrations of asymptomatic alanine or aspartate aminotransferase, or gamma-glutamyltransferase, without increased bilirubin, occurred in 11 (39%) of 28 patients who received at least 30 mg/day. 11 serious adverse events were reported in seven (25%) patients and included psychiatric disorders (six events in four patients), gait disturbance (one event), elevated liver aminotransferases (two events in two patients, one with agranulocytosis), and decline in neurological functioning (one event, likely due to natural disease progression although causality could not be ruled out). The seven serious adverse events categorised as psychiatric disorders and as gait disturbance were assessed as unlikely to be related to the study drug, whereas the remaining four events were possibly or probably related. INTERPRETATION: Our findings indicate that WTX101 might be a promising new therapeutic approach for Wilson's disease, with a unique mode of action. In view of its once-daily dose and favourable safety profile, WTX101 could improve the treatment of patients with this debilitating condition. FUNDING: Wilson Therapeutics AB. PMID- 28988936 TI - Fast digital 4pibeta-4pigamma coincidence counting with offline analysis at IRA. AB - IRA recently launched a project to digitize all the data acquisition systems it uses for primary radionuclide standardizations. It is well-known that the digital approach presents numerous advantages over the traditional analog electronics such as information losslessness, scalability, online and/or offline data processing, and it is also a solution to the growing difficulties to repair or renew ageing modules. As a first step in this wider program, our institute set-up a 4pibeta-4pigamma digital coincidence counting system, with FPGA (Field Programmable Gate Array)-based commercial boards from National Instruments (NI), to perform data acquisition and offline data analysis. Choosing all components and software from the same supplier provides a full compact and consistent electronic system. To demonstrate and validate the capacity of this system to standardize the activity of radioisotopes, we compare its predictions for the activity concentration of 133Ba, 166mHo and 18F solutions with the results from a coincidence counting system with analog electronics, as well as with the results from other primary methods and a secondary measurement performed with an IG11 ionization chamber (CIR, chambre d'ionization de reference) with an equivalent activity traceable to the Systeme International de Reference. PMID- 28988938 TI - Testosterone Therapy in a Man with Intermediate-risk Prostate Cancer: Pro. AB - The original prohibition of testosterone therapy for men with prostate cancer was based on outdated concepts developed more than 70 yr ago. Current evidence, although limited, provides consistently reassuring results that testosterone therapy may be reasonably offered to many men with prostate cancer. These men may experience valuable benefits in quality of life if they suffer from symptoms of testosterone deficiency (hypogonadism). PMID- 28988937 TI - Temporal trends and epidemiology of Staphylococcus aureus surgical site infection in the Swiss surveillance network: a cohort study. AB - BACKGROUND: Staphylococcus aureus is the leading pathogen in surgical site infections (SSI). AIM: To explore trends and risk factors associated with S. aureus SSI. METHODS: Risk factors for monomicrobial S. aureus SSI were identified from the Swiss multi-centre SSI surveillance system using multi-variate logistic regression. Both in-hospital and postdischarge SSI were identified using standardized definitions. FINDINGS: Over a six-year period, data were collected on 229,765 surgical patients, of whom 499 (0.22%) developed monomicrobial S. aureus SSI; 459 (92.0%) and 40 (8.0%) were due to meticillin-susceptible S. aureus (MSSA) and meticillin-resistant S. aureus (MRSA), respectively. There was a significant decrease in the rate of MSSA SSI (P = 0.007), but not in the rate of MRSA SSI (P = 0.70). Independent protective factors for S. aureus SSI were older age [>=75 years vs <50 years: odds ratio (OR) 0.60, 95% confidence interval (CI) 0.44-0.83], laparoscopy/minimally invasive surgery (OR 0.68, 95% CI 0.50 0.92), non-clean surgery [OR 0.78 (per increase in wound contamination class), 95% CI 0.64-0.94] and correct timing of pre-operative antibiotic prophylaxis (OR 0.80, 95% CI 0.65-0.98). Independent risk factors were male sex (OR 1.38, 95% CI 1.14-1.66), higher American Society of Anesthesiologists' score (per one-point increment: OR 1.30, 95% CI 1.13-1.51), re-operation for non-infectious reasons (OR 4.59, 95% CI 3.59-5.87) and procedure type: cardiac surgery, laminectomy, and hip or knee arthroplasty had two-to nine-fold increased odds of S. aureus SSI compared with other procedures. CONCLUSIONS: SSI due to S. aureus are decreasing and becoming rare events in Switzerland. High-risk procedures that may benefit from specific preventive measures were identified. Unfortunately, many of the independent risk factors are not easily modifiable. PMID- 28988939 TI - Susceptibility of wounded and intact black soldier fly Hermetia illucens (L.) (Diptera: Stratiomyidae) to entomopathogenic nematodes. AB - Production costs and limited regional availability are two key factors limiting the widespread adoption of entomopathogenic nematodes (Rhabditida: Heterorhabditidae and Steinernematidae) in biological control programs. We explore the potential of using black soldier fly larvae Hermetia illucens (L.) (Diptera: Stratiomyidae) as an alternative in vivo rearing host to the greater wax moth, Galleria mellonella (L.) (Lepidoptera: Pyralidae). We injured black soldier fly larvae to test the hypothesis that the tough cuticle was preventing the penetration of founding infective juveniles (IJs) into the host and egress of offspring from the cadaver. Injuring the black soldier fly larvae increased the infection rate, the number of nematodes entering a host, and the number of IJs harvested from a cadaver. Black soldier fly larvae, however, provided at most 10 fold less IJs compared to G. mellonella. In olfactometer assays, we assessed nematode behavioral responses to wounded black soldier fly larvae. Steinernema carpocapsae did not move towards the insects. Heterorhabditis bacteriophora was attracted to black soldier fly larvae but not G. mellonella. Heterorhabditis bacteriophora did not show a preference for injured black soldier fly larvae over non-injured larvae. Thus, increased colonization on wounded black soldier fly larvae was likely due to additional entry points rather than an increase in their apparency in the soil solution. PMID- 28988940 TI - Dual-lumen balloon to increase onyx venous penetration in the treatment of spinal dural arteriovenous fistulas. AB - PURPOSE: Spinal dural arteriovenous fistulas (sDAVF) are the most common spinal vascular lesions. The arterialization of the recipient vein results in venous hypertension and chronic ischemia. Intravascular injection of acrylic glue in order to occlude the draining vein is the principle of endovascular treatment, but a significant portion of embolization procedures do not succeed. We present our initial experience of endovascular balloon augmented embolization of sDAVF using a dual-lumen balloon. CLINICAL PRESENTATION: Three patients harboring sDAVF were submitted to endovascular treatment by onyx injection assisted by a double lumen balloon as the sole therapy. Control angiography demonstrated complete obliteration of the fistula in all cases with clinical improvement. CONCLUSION: Dual-lumen balloon onyx embolization of spinal dural arteriovenous fistulas appears to be an acceptable and feasible alternative. PMID- 28988941 TI - The economic impact of a nurse practitioner-directed lung cancer screening, incidental pulmonary nodule, and tobacco-cessation clinic. AB - OBJECTIVE: Lung cancer screening programs have become increasingly prevalent within the United States after the National Lung Screening Trial results. We aimed to review the financial impact after programmatic implementation of Advanced Registered Nurse Practitioner-led programs of Lung Cancer Screening and Tobacco Related Diseases, Incidental Pulmonary Nodule Clinic, and Tobacco Cessation Services. METHODS: We reviewed revenue from 2013 to 2016 by our nurse practitioner-led program. Encounters were queried for charges related to outpatient evaluation and management, professional procedures, and facility charges related to both outpatient and inpatient procedures. Revenue was normalized using 2016 data tables and the national Medicare conversion factor (35.8043). RESULTS: Our program evaluated 694 individuals, of whom 75% (518/694) are enrolled within the lung cancer-screening program. Overall revenue associated with the programs was $733,336. Outpatient evaluation and management generated revenue of $168,372. In addition, professional procedure revenue accounted for an additional $60,015 with facility revenue adding an additional $504,949. CONCLUSIONS: A nurse practitioner-led program of lung cancer screening, incidental pulmonary nodules, and tobacco-cessation services can provide additional revenue opportunities for a Thoracic Surgery and Interventional Pulmonology Division, as well as a health care system. The current national, median annual wage of a nurse practitioner is $98,190, and the cost associated directly to their salary (and benefits) may remain neutral or negative within certain programs. However, the larger economic benefit may be realized within the division and institution. This potential additional revenue appears related to evaluation of newly identified diseases and subsequent evaluations, procedures, and operations. PMID- 28988942 TI - Discussion. PMID- 28988943 TI - How addictive are gabapentin and pregabalin? A systematic review. AB - In the last ten years, gabapentin and pregabalin have been becoming dispensed broadly and sold on black markets, thereby, exposing millions to potential side effects. Meanwhile, several pharmacovigilance-databases have warned for potential abuse liabilities and overdose fatalities in association with both gabapentinoids. To evaluate their addiction risk in more detail, we conducted a systematic review on PubMed/Scopus and included 106 studies. We did not find convincing evidence of a vigorous addictive power of gabapentinoids which is primarily suggested from their limited rewarding properties, marginal notes on relapses, and the very few cases with gabapentinoid-related behavioral dependence symptoms (ICD-10) in patients without a prior abuse history (N=4). In support, there was no publication about people who sought treatment for the use of gabapentinoids. Pregabalin appeared to be somewhat more addictive than gabapentin regarding the magnitude of behavioral dependence symptoms, transitions from prescription to self-administration, and the durability of the self administrations. The principal population at risk for addiction of gabapentinoids consists of patients with other current or past substance use disorders (SUD), mostly opioid and multi-drug users, who preferred pregabalin. Pure overdoses of gabapentinoids appeared to be relative safe but can become lethal (pregabalin > gabapentin) in mixture with other psychoactive drugs, especially opioids again and sedatives. Based upon these results, we compared the addiction risks of gabapentin and pregabalin with those of traditional psychoactive substances and recommend that in patients with a history of SUD, gabapentinoids should be avoided or if indispensable, administered with caution by using a strict therapeutic and prescription monitoring. PMID- 28988944 TI - Efficacy of adding nutritional supplements in unipolar depression: A systematic review and meta-analysis. AB - In this article, we aimed to assess the efficacy of adjunctive administration of nutritional supplements to antidepressants by means of a systematic review and meta-analysis. The supplements included were inositol, vitamin D, folic acid, vitamin B12, S-adenosyl-L-methionine (SAMe), omega-3 polyunsaturated fatty acids (n-3 PUFA) and zinc. A structured database search (MEDLINE, EBSCO, CENTRAL, Web of Science) was performed using terms for the respective substances in conjunction with terms for depression and the mode of treatment ("add-on" OR "adjunctive" OR "augmentation"). Meta-analyses, randomized controlled trials (RCTs) and non-randomized comparative studies that investigated the supplements as an add-on in the treatment of clinically diagnosed MDD were included. Agents had to be added to an existing antidepressant regime (augmentation) or started simultaneously with the antidepressant (acceleration). For n-3 PUFAs, folic acid and zinc, new meta-analyses were performed as part of this work. Our meta analyses of 10 articles on n-3 PUFAs and four on zinc support their efficacy. For folic acid, our meta-analysis does not support efficacy. For n-3 PUFAs, sensitivity analysis showed no difference between acceleration and augmentation designs, but significant differences between individuals with or without comorbidities. For the remaining substances, only a few RCTs were available. The preliminary data on inositol was negative, while one RCT for vitamin D demonstrated positive results. For vitamin B12 one and for SAMe two RCTs and a few open trials are available reporting positive and mixed results. To summarize, for most of the substances, the available data is not yet sufficient or inconclusive. PMID- 28988945 TI - Neurodegeneration in diabetic retinopathy: Potential for novel therapies. AB - The complex pathology of diabetic retinopathy (DR) affects both vascular and neural tissue. The characteristics of neurodegeneration are well-described in animal models but have more recently been confirmed in the clinical setting, mostly by using non-invasive imaging approaches such as spectral domain optical coherence tomography (SD-OCT). The most frequent observations report loss of tissue in the nerve fiber layer and inner plexiform layer, confirming earlier findings from animal models. In several cases the reduction in inner retinal layers is reported in patients with little evidence of vascular lesions or macular edema, suggesting that degenerative loss of neural tissue in the inner retina can occur after relatively short durations of diabetes. Animal studies also suggest that neurodegeneration leading to retinal thinning is not limited to cell death and tissue loss but also includes changes in neuronal morphology, reduced synaptic protein expression and alterations in neurotransmission, including changes in expression of neurotransmitter receptors as well as neurotransmitter release, reuptake and metabolism. The concept of neurodegeneration as an early component of DR introduces the possibility to explore alternative therapies to prevent the onset of vision loss, including neuroprotective therapies and drugs targeting individual neurotransmitter systems, as well as more general neuroprotective approaches to preserve the integrity of the neural retina. In this review we consider some of the evidence for progressive retinal neurodegeneration in diabetes, and explore potential neuroprotective therapies. PMID- 28988946 TI - Compromise Not Required. PMID- 28988947 TI - Multiplexed Thiol Reactivity Profiling for Target Discovery of Electrophilic Natural Products. AB - Electrophilic groups, such as Michael acceptors, expoxides, are common motifs in natural products (NPs). Electrophilic NPs can act through covalent modification of cysteinyl thiols on functional proteins, and exhibit potent cytotoxicity and anti-inflammatory/cancer activities. Here we describe a new chemoproteomic strategy, termed multiplexed thiol reactivity profiling (MTRP), and its use in target discovery of electrophilic NPs. We demonstrate the utility of MTRP by identifying cellular targets of gambogic acid, an electrophilic NP that is currently under evaluation in clinical trials as anticancer agent. Moreover, MTRP enables simultaneous comparison of seven structurally diversified alpha,beta unsaturated gamma-lactones, which provides insights into the relative proteomic reactivity and target preference of diverse structural scaffolds coupled to a common electrophilic motif and reveals various potential druggable targets with liganded cysteines. We anticipate that this new method for thiol reactivity profiling in a multiplexed manner will find broad application in redox biology and drug discovery. PMID- 28988948 TI - Self-Assembly of 3D DNA Crystals Containing a Torsionally Stressed Component. AB - There is an increasing appreciation for structural diversity of DNA that is of interest to both DNA nanotechnology and basic biology. Here, we have explored how DNA responds to torsional stress by building on a previously reported two-turn DNA tensegrity triangle and demonstrating that we could introduce an extra nucleotide pair (np) into the original sequence without affecting assembly and crystallization. The extra np imposes a significant torsional stress, which is accommodated by global changes throughout the B-DNA duplex and the DNA lattice. The work reveals a near-atomic structure of naked DNA under a torsional stress of approximately 14%, and thus provides an example of DNA distortions that occur without a requirement for either an external energy source or the free energy available from protein or drug binding. PMID- 28988949 TI - Structure of the Guanidine III Riboswitch. AB - Riboswitches are structural elements found in mRNA molecules that couple small molecule binding to regulation of gene expression, usually by controlling transcription or translation. We have determined high-resolution crystal structures of the ykkC guanidine III riboswitch from Thermobifida fusca. The riboswitch forms a classic H-type pseudoknot that includes a triple helix that is continuous with a central core of conserved nucleotides. These form a left-handed helical ramp of inter-nucleotide interactions, generating the guanidinium cation binding site. The ligand is hydrogen bonded to the Hoogsteen edges of two guanine bases. The binding pocket has a side opening that can accommodate a small side chain, shown by structures with bound methylguanidine, aminoguanidine, ethylguanidine, and agmatine. Comparison of the new structure with those of the guanidine I and II riboswitches reveals that evolution generated three different structural solutions for guanidine binding and subsequent gene regulation, although with some common elements. PMID- 28988950 TI - Experience With the Absorb Bioresorbable Vascular Scaffold in Various Scenarios of Congenital Heart Disease. PMID- 28988951 TI - [Relationship between macronutrient and micronutrient intake and nutritional status of active older adults in Chillan, Chile]. AB - INTRODUCTION: Social participation by older adults is a health-protective element that promotes a normal nutritional status through the intake of appropriate nutrients that favour successful aging. MATERIAL AND METHODS: A cross-sectional analytical study was performed on a sample of 118 older adults. Food intake was measured using a 24-h recall questionnaire. The body mass index was used to evaluate the nutritional status. The information was analysed using uni- and bivariate descriptive statistics. Given the abnormal distribution of the responses, the Mann-Whitney and Kolgomorov-Smirnov statistical test were used to compare data at the significance level alpha=0.05. RESULTS: More than half (55%) of the women and 61% of men had a normal nutritional status. The calories and macronutrient intake were within the recommended ranges and unrelated to the nutritional status (P>.05). The micronutrients showed significant differences in relation to the nutritional status, broken down by gender and age, in the majority of vitamins and minerals. (P>.01). The group between 75-90 years old accomplished the recommended dietary allowance in every case. CONCLUSIONS: The active participation in organised community groups, the educational level of the older adults, and higher income, could be key factors to explain the good nutritional status of the group, and appears to be a good indicator of healthy aging. PMID- 28988952 TI - Uncommon and fatal case of cystoisosporiasis in a non HIV-immunosuppressed patient from a non-endemic country. AB - Cystoisospora belli (previously known as Isospora belli) is a tropical coccidian parasite sometimes leading to severe diarrhea in immunocompromised patients. Here we describe a fatal case of cystoisosporiasis in a non HIV-immunocompromised 71 year-old female with no recent travel history. Infection was either latent or potentially caused by the consumption of contaminated imported food from Asia. Diagnosis was made by microscopical detection of numerous C. belli oocysts in stools without specific staining. Treatment with TMP-SMZ slightly improved diarrhea within 3days, but dehydration subsequently led to acute decompensated heart failure and a fatal evolution. This report illustrates the possibility of severe cystoisosporiasis in non HIV-immunocompromised patients in a non-endemic country and highlights the risk of transmission through imported contaminated food consumption. PMID- 28988955 TI - Work-Related Quality of Life of US General Surgery Residents: Is It Really so Bad? AB - PURPOSE: The quality of working life of US surgical residents has not been studied, and given the complexity of interaction between work and personal life there is a need to assess this interaction. We utilized a validated Work Related Quality of Life (WRQoL) questionnaire to evaluate the perceived work-related quality of life of general surgery residents, using a large, nationally representative sample in the United States. METHODS: Between January 2016 and March 2016, all US general surgery residents enrolled in an ACGME general surgery training program were invited to participate. The WRQoL scale measures perceived quality of life covering six domains: General Well-Being (GWB), Home-Work Interface (HWI), Job and Career Satisfaction (JCS), Control at Work (CAW), Working Conditions (WCS) and Stress at Work (SAW). RESULTS: After excluding for missing data, the final analysis included 738 residents. The average age was 30 (+/-3) years, of whom 287 (38.9%) were female, 272 (36.9%) were from a community hospital, and 477 (64.6%) were juniors (postgraduate year <= 3). Demographically, the respondents matched expected percentages. When male and female residents were compared, males had statistically better HWI (p<0.001), better GWB (p = 0.03), more CAW (p = 0.0003) and WCS (p = 0.001). Junior residents had a lower JCS (p = 0.002) and CAW (p = 0.04) compared to seniors. There were no differences between university and community residents in any of the domains of WRQoL. Although residents were more stressed than other professions but the overall WRQoL was comparable. CONCLUSIONS: The nature of surgical residency and a surgical career may in fact be more "stressful" than other professions, yet may not translate into a worsened Quality of Life. Our findings suggest further study is needed to elucidate why female residents have or experience a lower perceived WRQoL than their male colleagues. PMID- 28988957 TI - Neocortical development. PMID- 28988956 TI - Instituting a Surgical Skills Competition Increases Technical Performance of Surgical Clerkship Students Over Time. AB - INTRODUCTION: Surgical skills training varies greatly between institutions and is often left to students to approach independently. Although many studies have examined single interventions of skills training, no data currently exists about the implementation of surgical skills assessment as a component of the medical student surgical curriculum. We created a technical skills competition and evaluated its effect on student surgical skill development. METHODS: Second-year medical students enrolled in the surgery clerkship voluntarily participated in a surgical skills competition consisting of knot tying, laparoscopic peg transfer, and laparoscopic pattern cut. Winning students were awarded dinner with the chair of surgery and a resident of their choice. Individual event times and combined times were recorded and compared for students who completed without disqualification. Disqualification included compromising cutting pattern, dropping a peg out of the field of vision, and incorrect knot tying technique. Timed performance was compared for 2 subsequent academic years using Mann-Whitney U test. RESULTS: Overall, 175 students competed and 71 students met qualification criteria. When compared by academic year, 2015 to 2016 students (n = 34) performed better than 2014 to 2015 students (n = 37) in pattern cut (133s vs 167s, p = 0.040), peg transfer (66s vs 101s, p < 0.001), knot tying (28s vs 30s, p = 0.361), and combined time (232s vs 283s, p = 0.009). The best time for each academic year also improved (105s vs 110s). Fundamentals of Laparoscopic Surgery proficiency standards for examined tasks were achieved by 70% of winning students. CONCLUSIONS: Implementation of an incentivized surgical skills competition improves student technical performance. Further research is needed regarding long-term benefits of surgical competitions for medical students. PMID- 28988954 TI - F-RAG: Generating Atomic Coordinates from RNA Graphs by Fragment Assembly. AB - Coarse-grained models represent attractive approaches to analyze and simulate ribonucleic acid (RNA) molecules, for example, for structure prediction and design, as they simplify the RNA structure to reduce the conformational search space. Our structure prediction protocol RAGTOP (RNA-As-Graphs Topology Prediction) represents RNA structures as tree graphs and samples graph topologies to produce candidate graphs. However, for a more detailed study and analysis, construction of atomic from coarse-grained models is required. Here we present our graph-based fragment assembly algorithm (F-RAG) to convert candidate three dimensional (3D) tree graph models, produced by RAGTOP into atomic structures. We use our related RAG-3D utilities to partition graphs into subgraphs and search for structurally similar atomic fragments in a data set of RNA 3D structures. The fragments are edited and superimposed using common residues, full atomic models are scored using RAGTOP's knowledge-based potential, and geometries of top scoring models is optimized. To evaluate our models, we assess all-atom RMSDs and Interaction Network Fidelity (a measure of residue interactions) with respect to experimentally solved structures and compare our results to other fragment assembly programs. For a set of 50 RNA structures, we obtain atomic models with reasonable geometries and interactions, particularly good for RNAs containing junctions. Additional improvements to our protocol and databases are outlined. These results provide a good foundation for further work on RNA structure prediction and design applications. PMID- 28988953 TI - Meddling with Fate: The Proteasomal Deubiquitinating Enzymes. AB - Three deubiquitinating enzymes-Rpn11, Usp14, and Uch37-are associated with the proteasome regulatory particle. These enzymes allow proteasomes to remove ubiquitin from substrates before they are translocated into the core particle to be degraded. Although the translocation channel is too narrow for folded proteins, the force of translocation unfolds them mechanically. As translocation proceeds, ubiquitin chains bound to substrate are drawn to the channel's entry port, where they can impede further translocation. Rpn11, situated over the port, can remove these chains without compromising degradation because substrates must be irreversibly committed to degradation before Rpn11 acts. This coupling between deubiquitination and substrate degradation is ensured by the Ins-1 loop of Rpn11, which controls ubiquitin access to its catalytic site. In contrast to Rpn11, Usp14 and Uch37 can rescue substrates from degradation by promoting substrate dissociation from the proteasome prior to the commitment step. Uch37 is unique in being a component of both the proteasome and a second multisubunit assembly, the INO80 complex. However, only recruitment into the proteasome activates Uch37. Recruitment to the proteasome likewise activates Usp14. However, the influence of Usp14 on the proteasome depends on the substrate, due to its marked preference for proteins that carry multiple ubiquitin chains. Usp14 exerts complex control over the proteasome, suppressing proteasome activity even when inactive in deubiquitination. A major challenge for the field will be to elucidate the specificities of Rpn11, Usp14, and Uch37 in greater depth, employing not only model in vitro substrates but also their endogenous targets. PMID- 28988958 TI - Mycobacterium abscessus and massiliense lung infection during macrolide treatment for bronchiolitis obliterans after allogeneic hematopoietic stem cell transplantation. AB - In patients undergoing allogeneic hematopoietic stem cell transplantation (allo SCT), post-transplant lung infection is critical for their prognosis. Mycobacterium abscessus complex is not fully recognized as a nontuberculous mycobacteria (NTM) pathogen of post-SCT lung infection. Here, we present three post-allogeneic SCT patients who developed pulmonary infection caused by M. abscessus complex including M. abscessus and M. massiliense. In all three cases, macrolide antibiotics had been administered for bronchiolitis obliterans syndrome (BOS) before the confirmation of their infection, and macrolide resistance was noted in the M. abscessus isolates, one of which resulted in an unfavorable treatment outcome. It is important to consider M. abscessus lung infection as well as other NTM in patients receiving allo-SCT, particularly those receiving macrolide therapy for BOS. PMID- 28988959 TI - Decision-making frameworks and considerations for informing coverage decisions for healthcare interventions: a critical interpretive synthesis. AB - OBJECTIVE: To guide decision-making about whether or not to pay for a new healthcare intervention, a number of existing frameworks systematically weigh scientific evidence, cost, and social and ethical values. Each framework has strengths and limitations. This study aims to review and summarize available frameworks and generate an integrated framework, if and where applicable, highlighting particular issues faced with expensive but effective and desirable healthcare interventions. STUDY DESIGN AND SETTING: We conducted a critical interpretive synthesis to inform decision-making about healthcare interventions. We updated prior systematic reviews on decision-making frameworks through 2015. Purposive sampling identified relevant constructs and considerations to facilitate decision-making. RESULTS: Of 2,980 references, we purposively sampled 19 frameworks. The new framework, which built on the GRADE Evidence to Decision framework, included burden of disease, benefits and harms, values and preferences, resource use, equity, acceptability, and feasibility. Modifications to the Evidence to Decision framework included adding limitations of alternative technologies considerations in use (expanding benefits and harms) and broadening acceptability and feasibility constructs to include political and health system factors. No modifications appeared necessary to address the situation of effective but expensive and desirable interventions. CONCLUSION: Guideline developers, health technology assessment producers, and decision-makers can use our integrated framework to inform decision-making about healthcare interventions. PMID- 28988960 TI - PDIM and SL1 accumulation in Mycobacterium tuberculosis is associated with mce4A expression. AB - Lipid metabolism forms the heart and soul of Mycobacterium tuberculosis life cycle. Starting from macrophage invasion at cholesterol rich micro-domains to a sustainable survival for infection by utilizing cholesterol, Mycobacterium displays the nexus of metabolic pathways around host derived lipids. mce4 operon acts as cholesterol import system in M. tuberculosis and here we demonstrate role of mce4A gene of this operon in cholesterol catabolism. Here M. tuberculosis H37Rv overexpressing Rv3499c (mce4A) recombinant was used as a model to decipher the metabolic flux during intake and utilization of host lipids by mycobacteria. We analysed the impact of mce4A expression on carbon shift initiated during cholesterol utilization necessary for long term survival of mycobacterium. Through transcriptional analysis, upregulation in methylcitrate cycle (MCC) and methylmalonyl pathway (MMP) genes was observed in Rv3499c overexpressing recombinants of M. tuberculosis H37Rv. Up-regulation of methylmalonyl pathway associated enzyme encoding genes increased accumulation of virulence associated mycobacterial lipids phthiocerol dimycocerates (PDIM) and sulfolipid (SL1). We demonstrate that MCC and MMP associated enzyme encoding genes are upregulated upon mce4A overexpression and lead to enhanced accumulation of PDIM and SL1 which are responsible for pathogenicity of M. tuberculosis. PMID- 28988961 TI - Comprehensive genome-wide analysis of Glutathione S-transferase gene family in potato (Solanum tuberosum L.) and their expression profiling in various anatomical tissues and perturbation conditions. AB - Glutathione S-transferases (GSTs) are ubiquitous enzymes which play versatile functions including cellular detoxification and stress tolerance. In this study, a comprehensive genome-wide identification of GST gene family was carried out in potato (Solanum tuberosum L.). The result demonstrated the presence of at least 90 GST genes in potato which is greater than any other reported species. According to the phylogenetic analyses of Arabidopsis, rice and potato GST members, GSTs could be subdivided into ten different classes and each class is found to be highly conserved. The largest class of potato GST family is tau with 66 members, followed by phi and lambda. The chromosomal localization analysis revealed the highly uneven distribution of StGST genes across the potato genome. Transcript profiling of 55 StGST genes showed the tissue-specific expression for most of the members. Moreover, expression of StGST genes were mainly repressed in response to abiotic stresses, while largely induced in response to biotic and hormonal elicitations. Further analysis of StGST gene's promoter identified the presence of various stress responsive cis-regulatory elements. Moreover, one of the highly stress responsive StGST members, StGSTU46, showed strong affinity towards flurazole with lowest binding energy of -7.6kcal/mol that could be used as antidote to protect crop against herbicides. These findings will facilitate the further functional and evolutionary characterization of GST genes in potato. PMID- 28988962 TI - Prehospital cooling to improve successful targeted temperature management after cardiac arrest: A randomized controlled trial. AB - RATIONALE: Targeted temperature management (TTM) improves survival with good neurological outcome after out-of-hospital cardiac arrest (OHCA), but is delivered inconsistently and often with delay. OBJECTIVE: To determine if prehospital cooling by paramedics leads to higher rates of 'successful TTM', defined as achieving a target temperature of 32-34 degrees C within 6h of hospital arrival. METHODS: Pragmatic RCT comparing prehospital cooling (surface ice packs, cold saline infusion, wristband reminders) initiated 5min after return of spontaneous circulation (ROSC) versus usual resuscitation and transport. The primary outcome was rate of 'successful TTM'; secondary outcomes were rates of applying TTM in hospital, survival with good neurological outcome, pulmonary edema in emergency department, and re-arrest during transport. RESULTS: 585 patients were randomized to receive prehospital cooling (n=279) or control (n=306). Prehospital cooling did not increase rates of 'successful TTM' (30% vs 25%; RR, 1.17; 95% confidence interval [CI] 0.91-1.52; p=0.22), but increased rates of applying TTM in hospital (68% vs 56%; RR, 1.21; 95%CI 1.07-1.37; p=0.003). Survival with good neurological outcome (29% vs 26%; RR, 1.13, 95%CI 0.87-1.47; p=0.37) was similar. Prehospital cooling was not associated with re arrest during transport (7.5% vs 8.2%; RR, 0.94; 95%CI 0.54-1.63; p=0.83) but was associated with decreased incidence of pulmonary edema in emergency department (12% vs 18%; RR, 0.66; 95%CI 0.44-0.99; p=0.04). CONCLUSIONS: Prehospital cooling initiated 5min after ROSC did not increase rates of achieving a target temperature of 32-34 degrees C within 6h of hospital arrival but was safe and increased application of TTM in hospital. PMID- 28988963 TI - Defining Novel and Practical Metrics to Assess the Deliverables of Multiparametric Magnetic Resonance Imaging/Ultrasound Fusion Prostate Biopsy. AB - PURPOSE: Multiparametric magnetic resonance/ultrasound targeted prostate biopsy is touted as a tool to improve prostate cancer care and yet its true clinical usefulness over transrectal ultrasound guided prostate biopsy has not been systematically analyzed. We introduce 2 metrics to better quantify and report the deliverables of targeted biopsy. MATERIALS AND METHODS: We reviewed our prospective database of patients who underwent simultaneous multiparametric magnetic resonance/ultrasound targeted prostate biopsy and transrectal ultrasound guided prostate biopsy. Actionable intelligence metric was defined as the proportion of patients in whom targeted biopsy provided actionable information over transrectal ultrasound guided prostate biopsy. Reduction metric was defined as the proportion of men in whom transrectal ultrasound guided prostate biopsy could have been omitted. We compared metrics in our cohort with those in prior reports. RESULTS: A total of 371 men were included in study. The actionable intelligence and reduction metrics were 22.2% and 83.6% in biopsy naive cases, 26.7% and 84.2% in prior negative transrectal ultrasound guided prostate biopsy cases, and 24% and 77.5%, respectively, in active surveillance cases. No significant differences were observed among the groups in the actionable intelligence metric and the reduction metric (p = 0.89 and 0.27, respectively). The actionable intelligence metric was 25.0% for PI-RADSTM (Prostate Imaging Reporting and Data System) 3, 27.5% for PI-RADS 4 and 21.7% for PI-RADS 5 lesions (p = 0.73). Transrectal ultrasound guided prostate biopsy could have been avoided in more patients with PI-RADS 3 compared to PI-RADS 4/5 lesions (reduction metric 92.0% vs 76.7%, p <0.01). Our results compare favorably to those of other reported series. CONCLUSIONS: The actionable intelligence metric and the reduction metric are novel, clinically relevant quantification metrics to standardize the reporting of multiparametric magnetic resonance/ultrasound targeted prostate biopsy deliverables. Targeted biopsy provides actionable information in about 25% of men. Reduction metric assessment highlights that transrectal ultrasound guided prostate biopsy may only be omitted after carefully considering the risk of missing clinically significant cancers. PMID- 28988965 TI - Do estrogens enhance activation of brown and beiging of adipose tissues? AB - Obesity and its associated co-morbidities are worldwide public health concerns. Obesity is characterized by excessive adipose tissue accumulation; however, it is important to recognize that human and rodent adipose tissues are made up of several distinct adipose tissue sub-types. White adipose tissue (WAT) is considered the prototypical fat cell, due to its capacity and capability to store large amounts of lipid. In contrast, brown adipose tissue (BAT) oxidizes substrates to generate heat. BAT contains more mitochondria than WAT and express uncoupling protein-1 (UCP1), which mediates BAT thermogenesis. A third sub-type of adipose tissue, Brown-in-white (BRITE)/beige adipocytes arise from WAT upon adrenergic stimulation and resembles BAT functionally. The energy burning feature of BAT/beige cells, combined with evidence of an inverse-correlation between BAT/beige adipose tissue and obesity have given rise to the hypothesis that obesity may be linked to BAT/beige 'malfunction'. Females have more BAT and perhaps an enhanced capacity to beige their adipose tissue when compared to males. Multiple signal pathways are capable of activating BAT thermogenesis and beiging of WAT; here, we discuss the potential role of estrogens in enhancing and mediating these factors to enhance adipose tissue thermogenesis. PMID- 28988964 TI - Epidemiology of Bacteremia in Febrile Infants Aged 60 Days and Younger. AB - STUDY OBJECTIVE: To describe the current epidemiology of bacteremia in febrile infants 60 days of age and younger in the Pediatric Emergency Care Applied Research Network (PECARN). METHODS: We conducted a planned secondary analysis of a prospective observational study of febrile infants 60 days of age and younger presenting to any of 26 PECARN emergency departments (2008 to 2013) who had blood cultures obtained. We excluded infants with significant comorbidities or critically ill appearance. The primary outcome was prevalence of bacteremia. RESULTS: Of 7,335 screened infants, 4,778 (65.1%) had blood cultures and were enrolled. Of these patients, 84 had bacteremia (1.8%; 95% confidence interval [CI] 1.4% to 2.2%). The prevalence of bacteremia in infants aged 28 days or younger (47/1,515) was 3.1% (95% CI 2.3% to 4.1%); in infants aged 29 to 60 days (37/3,246), 1.1% (95% CI 0.8% to 1.6%). Prevalence differed by week of age for infants 28 days of age and younger (0 to 7 days: 4/156, 2.6%; 8 to 14 days: 19/356, 5.3%; 15 to 21 days: 15/449, 3.3%; and 22 to 28 days: 9/554, 1.6%). The most common pathogens were Escherichia coli (39.3%; 95% CI 29.5% to 50.0%) and group B streptococcus (23.8%; 95% CI 16.0% to 33.9%). Bacterial meningitis occurred in 19 of 1,515 infants 28 days of age and younger (1.3%; 95% CI 0.8% to 2.0%) and 5 of 3,246 infants aged 29 to 60 days (0.2%; 95% CI 0.1% to 0.4%). Of 84 infants with bacteremia, 36 (42.9%; 95% CI 32.8% to 53.5%) had urinary tract infections (E coli 83%); 11 (13.1%; 95% CI 7.5% to 21.9%) had bacterial meningitis. CONCLUSION: The prevalence of bacteremia and meningitis among febrile infants 28 days of age and younger is high and exceeds that observed in infants aged 29 to 60 days. E coli and group B streptococcus are the most common bacterial pathogens. PMID- 28988966 TI - Murine social stress results in long lasting voiding dysfunction. AB - Repeated exposure to social stress shifts the voiding phenotype in male mice leading to bladder wall remodeling and is associated with increased expression of the stress neuropeptide, corticotropin-releasing factor (CRF) in Barrington's nucleus neurons. In these studies, we set out to determine if the voiding phenotype could recover upon removal from the stressor. Male mice were exposed for 1h daily to an aggressor and the voiding phenotype was assessed at one month followed by randomization to three groups. One group underwent immediate sacrifice. Two groups were allowed a one month recovery from the social stress exposure with or without the addition of fluoxetine (1.2mg/ml) in their drinking water and repeat voiding patterns were measured prior to sacrifice. Social stress significantly increased bladder mass, bladder mass corrected for body weight, voided volumes, and decreased urinary frequency. The abnormal voiding phenotype persisted after a 1month recovery with no effect from the addition of fluoxetine. CRF mRNA in Barrington's nucleus was increased by social stress and remained elevated following recovery with no effect from the addition of fluoxetine. The mRNA and protein expression for the alpha 1 chains of type 1 and type III collagen was unchanged across all groups suggesting that changes in the extracellular matrix of the bladder are not responsible for the voiding phenotype. This persisting voiding dysfunction correlates with the persistent elevation of CRF mRNA expression in Barrington's nucleus. PMID- 28988967 TI - Prenatal stress suppresses the prefrontal and amygdaline EEG changes associated with a sexually-motivated state in male rats. AB - The medial prefrontal cortex (mPFC) and basolateral amygdala (BLA) participate in the modulation of several motivated behaviors, such as the sexual behavior. Both structures are sensitive to stress when it is experienced mainly in critical periods of the life-cycle, such as the prenatal period. This study evaluated the effects of prenatal stress on electroencephalographic activity (EEG) of the mPFC and BLA during sexual motivation. EEG was recorded in the mPFC and BLA of male rats assigned to either a prenatally-stressed group (SG, dam immobilized from days 14 to 21of pregnancy), or a control group (CG), during the following conditions: awake-quiet state without sexual motivation, and awake-quiet state with sexual motivation. Compared to CG, fewer SG subjects presented copulatory responses and their levels of sexual motivation were lower. The CG subjects with sexual motivation showed a higher absolute power (AP) of the 14-30Hz band in the left mPFC and BLA than those without sexual motivation. The SG showed a lower AP of the 4-7 and 8-13Hz bands in the left BLA. Thus, prenatal stress suppressed the prefrontal and amygdaline EEG changes associated with a sexually-motivated state. EEG data show that stress affects the functioning of these two brain structures and so could interfere with the adequate processing of sexual stimuli. These findings contribute to understanding the brain mechanisms that underlie the effect of prenatal stress on the processing of sexual stimuli in male rats. PMID- 28988968 TI - KiSS1 gene as a novel mediator of TGFbeta-mediated cell invasion in triple negative breast cancer. AB - The invasive and metastatic phenotypes of breast cancer correlate with high recurrence rates and poor survival outcomes. Transforming growth factor-beta (TGFbeta) promotes tumor progression and metastasis in aggressive breast cancer. Here, we identified the kisspeptin KiSS1 as a downstream target of canonical TGFbeta/Smad2 pathway in triple negative breast cancer cells. We also found KiSS1 expression to be required for TGFbeta-induced cancer cell invasion. Indeed, knockdown expression of KiSS1 blocked TGFbeta-mediated cancer cell invasion as well as metalloproteinase (MMP9) expression and activity. Interestingly, Kisspeptin-10 (KP-10), the smallest active form of kisspeptin also stimulates cancer cell invasive behavior through activation of MAPK/Erk pathway. We described a positive feedback loop between KiSS1 and p21 downstream of TGFbeta, further contributing to TGFbeta-induced cancer cell invasion. Lastly, we explored both the clinical utility of KiSS1 as a lymph node involvement predictive tool and its potential as a therapeutic target. We found KiSS1 high expression to correlate with lymph node positive status. Furthermore, blocking KiSS1 using a specific small peptide antagonist (p234) impaired TGFbeta-mediated cell invasion and MMP9 induction. Together, our results define an essential role of KiSS1 in regulating TGFbeta pro-invasive effects and define KiSS1 as a therapeutic new target for triple negative breast cancer. PMID- 28988970 TI - Effects of berberine, curcumin, resveratrol alone and in combination with chemotherapeutic drugs and signal transduction inhibitors on cancer cells-Power of nutraceuticals. AB - Over the past fifty years, society has become aware of the importance of a healthy diet in terms of human fitness and longevity. More recently, the concept of the beneficial effects of certain components of our diet and other compounds, that are consumed often by different cultures in various parts of the world, has become apparent. These "healthy" components of our diet are often referred to as nutraceuticals and they can prevent/suppress: aging, bacterial, fungal and viral infections, diabetes, inflammation, metabolic disorders and cardiovascular diseases and have other health-enhancing effects. Moreover, they are now often being investigated because of their anti-cancer properties/potentials. Understanding the effects of various natural products on cancer cells may enhance their usage as anti-proliferative agents which may be beneficial for many health problems. In this manuscript, we discuss and demonstrate how certain nutraceuticals may enhance other anti-cancer drugs to suppress proliferation of cancer cells. PMID- 28988971 TI - Voice Outcomes after Radiotherapy Treatment for Early Glottic Cancer: Long-Term Follow-Up. AB - OBJECTIVES: The aim of this study was to investigate long-term voice outcomes and voice-related quality of life (QOL) for early glottic cancer treated with radiotherapy. STUDY DESIGN: Long-term exploratory follow-up study of a prospective patient cohort comparing outcomes at a mean of 11 years postradiotherapy with the original 1-year posttreatment results. METHOD: Eight patients completed voice tasks for auditory perception and acoustic and aerodynamic measures. Patient-reported voice-related QOL (VR-QOL) and voice quality were measured. Changes in outcomes over time were analysed using repeated measures linear mixed models. RESULTS: Acoustic and aerodynamic outcomes remained stable from 1 year postradiotherapy to long-term follow-up, with only jitter mildly increasing from 1.9% at 1 year posttreatment to 2.8% (difference = 1.0%, 95% confidence interval [CI] = 0.1-1.9). Perceptually, voice remained relatively stable with only phonation breaks slightly increasing within the normal range, from 1.1 to 1.7 (difference = 0.6, 95% CI = 0.3-0.9) and breathy quality increasing from normal to slight impairment, with scores increasing from 1.8 to 2.4 (difference = 0.6, 95% CI = 0.3-1.1). QOL scores indicate a good level of VR QOL that were unchanged at long-term follow-up when compared with 1 year posttreatment. CONCLUSIONS: Improvement in voice outcomes found at 1 year postradiotherapy were largely maintained long term, with only minor changes observed. QOL scores indicate that a high level of VR-QOL was maintained many years after curative radiotherapy. PMID- 28988972 TI - Arginine vasopressin antagonizes the effects of prostaglandin E2 on the spontaneous activity of warm-sensitive and temperature-insensitive neurons in the medial preoptic area in rats. AB - Arginine vasopressin (AVP) plays an important role in thermoregulation and antipyresis. We have demonstrated that AVP could change the spontaneous activity of thermosensitive and temperature insensitive neurons in the preoptic area. However, whether AVP influences the effects of prostaglandin E2 (PGE2) on the spontaneous activity of neurons in the medial preoptic area (MPO) remains unclear. Our experiment showed that PGE2 decreased the spontaneous activity of warm-sensitive neurons, and increased that of low-slope temperature-insensitive neurons in the MPO. AVP attenuated the inhibitory effect of PGE2 on warm sensitive neurons, and reversed the excitatory effect of PGE2 on low-slope temperature-insensitive neurons, demonstrating that AVP antagonized the effects of PGE2 on the spontaneous activity of these neurons. The effect of AVP was suppressed by an AVP V1a receptor antagonist, suggesting that V1a receptor mediated the action of AVP. We also demonstrated that AVP attenuated the PGE2 induced decrease in the prepotential's rate of rise in warm-sensitive neurons and the PGE2-induced increase in that in low-slope temperature-insensitive neurons through the V1a receptor. Together, these data indicated that AVP antagonized the PGE2-induced change in the spontaneous activity of warm-sensitive and low-slope temperature-insensitive neurons in the MPO partly by reducing the PGE2-induced change in the prepotential of these neurons in a V1a receptor-dependent manner. PMID- 28988969 TI - Fetal alcohol spectrum disorders: Zebrafish in the analysis of the milder and more prevalent form of the disease. AB - Fetal Alcohol Spectrum Disorders (FASD) represent a large unmet medical need. Exposure of the developing human embryo to alcohol can lead to life-long suffering. Despite the well documented deleterious effects of alcohol on the developing fetus, pregnant women continue to drink alcohol, and FASD remains the leading cause of preventable mental retardation and other behavioral abnormalities. Particularly prevalent are the milder forms of the disease cluster, representing children who do not show obvious physical signs and who may be undiagnosed or misdiagnosed. To develop treatment and diagnostic tools, researchers have turned to animal models. The zebrafish is becoming one of the leading biomedical research organisms that may facilitate discovery of the biological mechanisms underlying this disease and the identification of biomarkers that may be used for diagnosis. Here we review the latest advances of this field, mostly focussing on the discoveries made in our own laboratory and others with zebrafish employed to analyze the effects of moderate to low level of exposure to alcohol. We argue that the zebrafish represents unique advantages, and adding information obtained with this species to the mix of other animal models will significantly increase translational relevance of animal biomedical research for the analysis of human FASD. PMID- 28988973 TI - Comparative connectomics: Mapping the inter-individual variability of connections within the regions of the human brain. AB - The human braingraph, or connectome is a description of the connections of the brain: the nodes of the graph correspond to small areas of the gray matter, and two nodes are connected by an edge if a diffusion MRI-based workflow finds fibers between those brain areas. We have constructed 1015-vertex graphs from the diffusion MRI brain images of 392 human subjects and compared the individual graphs with respect to several different areas of the brain. The inter-individual variability of the graphs within different brain regions was discovered and described. We have found that the frontal and the limbic lobes are more conservative, while the edges in the temporal and occipital lobes are more diverse. Interestingly, a "hybrid" conservative and diverse distribution was found in the paracentral lobule and the fusiform gyrus. Smaller cortical areas were also evaluated: precentral gyri were found to be more conservative, and the postcentral and the superior temporal gyri to be very diverse. Similar studies concerning the human genome discovered more and less conservative sections of the DNA, opening up entirely new fields in genomics. We think that the present study is the first step in this direction in human connectomics. The clinical significance of the conservativity of a given cerebral area could be the higher sensitivity for traumas and developmental or neuro-degenerative events than the less conservative areas. PMID- 28988974 TI - BDNF Val66Met polymorphism modulates the effect of loneliness on white matter microstructure in young adults. AB - Loneliness is a common experience. Susceptibility to loneliness is a stable trait and is heritable. Previous studies have suggested that loneliness may impact regional gray matter density and brain activation to social stimuli, but its relation to white matter structure and how it may interact with genetic factors remains unclear. In this study, we investigated whether and how a common polymorphism (Val66Met) in the brain-derived neurotrophic factor gene modulated the association between loneliness and white matter microstructure in 162 young adults. The tract-based spatial statistics analyses revealed that the relationships between loneliness and white matter microstructures were significantly different between Val/Met heterozygotes and Val/Val homozygotes. Specifically, loneliness was significantly correlated with reduced fractional anisotropy and increased radial diffusivity in widespread white matter fibers within Val/Met heterozygotes. It was also significantly correlated with increased radial diffusivity in Met/Met genotypes but showed no significant association with white matter measures in Val/Val genotypes. Furthermore, the associations between loneliness and fractional anisotropy (or radial diffusivity) in Val/Met heterozygotes turned out to be global effects. These results provide evidence that loneliness may interact with the BDNF Val66Met polymorphism to shape the microstructures of white matter, and the Val/Met heterozygotes may be more susceptible to social environment. PMID- 28988975 TI - Hydrogen peroxide (H2O2) suppresses hair growth through downregulation of beta catenin. PMID- 28988976 TI - Role of endogenous melatoninergic system in development of hyperalgesia and tolerance induced by chronic morphine administration in rats. AB - Morphine is a widely used analgesic for various types of pain. However, its efficacy is impeded by development of hyperalgesia and tolerance. Melatonin has antinociceptive effect and is involved in morphine-induced hyperalgesia and tolerance but the mechanism of its involvement remains to be defined. In this study, we established a rat model of morphine-induced hyperalgesia and tolerance. We determined the serum level of melatonin and expression of MU-opioid receptor (MOR), melatonin receptor (MT1, MT2) and protein kinase C gamma(PKCgamma) in the spinal dorsal horn of the rats with morphine-induced hyperalgesia and tolerance. Comparing with control group (n=6), the group (n=6) of rats with morphine-induced hyperalgesia and tolerance exhibited a significant lower serum melatonin level, reduction in expression of the MT1, but up-regulation of the PKCgamma in the spinal dorsal horn. These results may facilitate revealing the mechanism of opioid-induced hyperalgesia and tolerance and exploring new therapeutic remedy for pain management. PMID- 28988977 TI - Pulmonary Rehabilitation in a Patient With Bronchiectasis and Underlying Cerebral Palsy: A Case Presentation. AB - : Bronchiectasis is a chronic pulmonary disease characterized by the permanent dilatation of the airways, with recurrent infections. As the disease progresses, extrapulmonary symptoms manifest. If the patient with bronchiectasis has an underlying central nervous system disease such as cerebral palsy (CP), extrapulmonary functions decline faster. The co-occurrence of these 2 diseases may make care more complex, and there have been no reports about pulmonary rehabilitation (PR) in this class of patients. Here, we present a patient with bronchiectasis and underlying CP who showed marked improvement of pulmonary function and clinical symptoms after 6 weeks of a patient-specific intensive PR program. LEVEL OF EVIDENCE: IV. PMID- 28988978 TI - Isolated Neck Extensor Myopathy: A Case Presentation of Rapid Onset and Spontaneous Recovery. AB - : Patients presenting with a chin-on-chest deformity, or dropped head syndrome, may have a diagnosis of isolated neck extensor myopathy (INEM). INEM is a diagnosis of exclusion occurring primarily in elderly patients. INEM usually has a benign progression, which may involve the shoulder girdle but does not advance to other muscle groups. Patients without an inflammatory etiology typically experience minimal or no recovery of their symptoms. Dropped head syndrome has various implications on a patient's quality of life and activities of daily living. We present a unique case of INEM with rapid onset and complete clinical recovery within a time frame of 4 months. LEVEL OF EVIDENCE: V. PMID- 28988980 TI - Important Considerations for Studies of Circulating MicroRNAs in Clinical Samples. PMID- 28988981 TI - The typical RB76 recombination breakpoint of the invasive recombinant tomato yellow leaf curl virus of Morocco can be generated experimentally but is not positively selected in tomato. AB - TYLCV-IS76 is an unusual recombinant between the highly recombinogenic tomato yellow leaf curl virus (TYLCV) and tomato yellow leaf curl Sardinia virus (TYLCSV), two Mediterranean begomoviruses (Geminiviridae). In contrast with the previously reported TYLCV/TYLCSV recombinants, it has a TYLCSV derived fragment of only 76 nucleotides, and has replaced its parental viruses in natural conditions (Morocco, Souss region). The viral population shift coincided with the deployment of the popular Ty-1 resistant tomato cultivars, and according to experimental studies, has been driven by a strong positive selection in such resistant plants. However, although Ty-1 cultivars were extensively used in Mediterranean countries, TYLCV-IS76 was not reported outside Morocco. This, in combination with its unusual recombination pattern suggests that it was generated through a rare and possibly multistep process. The potential generation of a recombination breakpoint (RB) at locus 76 (RB76) was investigated over time in 10 Ty-1 resistant and 10 nearly isogenic susceptible tomato plants co-inoculated with TYLCV and TYLCSV clones. RB76 could not be detected in the recombinant progeny using the standard PCR/sequencing approach that was previously designed to monitor the emergence of TYLCV-IS76 in Morocco. Using a more sensitive PCR test, RB76 was detected in one resistant and five susceptible plants. The results are consistent with a very low intra-plant frequency of RB76 bearing recombinants throughout the test and support the hypothesis of a rare emergence of TYLCV-IS76. More generally, RBs were more scattered in resistant than in susceptible plants and an unusual RB at position 141 (RB141) was positively selected in the resistant cultivar; interestingly, RB141 bearing recombinants were detected in resistant tomato plants from the field. Scenarios of TYLCV-IS76 pre-emergence are proposed. PMID- 28988979 TI - IRX3 Promotes the Browning of White Adipocytes and Its Rare Variants are Associated with Human Obesity Risk. AB - BACKGROUND: IRX3 was recently reported as the effector of the FTO variants. We aimed to test IRX3's roles in the browning program and to evaluate the association between the genetic variants in IRX3 and human obesity. METHODS: IRX3 expression was examined in beige adipocytes in human and mouse models, and further validated in induced beige adipocytes. The browning capacity of primary preadipocytes was assessed with IRX3 knockdown. Luciferase reporter analysis and ChIP assay were applied to investigate IRX3's effects on UCP1 transcriptional activity. Moreover, genetic analysis of IRX3 was performed in 861 young obese subjects and 916 controls. RESULTS: IRX3 expression was induced in the browning process and was positively correlated with the browning markers. IRX3 knockdown remarkably inhibited UCP1 expression in induced mouse and human beige adipocytes, and also repressed the uncoupled oxygen consumption rate. Further, IRX3 directly bound to UCP1 promoter and increased its transcriptional activity. Moreover, 17 rare heterozygous missense/frameshift IRX3 variants were identified, with a significant enrichment in obese subjects (P=0.038, OR=2.27; 95% CI, 1.02-5.05). CONCLUSIONS: IRX3 deficiency repressed the browning program of white adipocytes partially by regulating UCP1 transcriptional activity. Rare variants of IRX3 were associated with human obesity. PMID- 28988982 TI - Phylogenetic analysis of Human papillomavirus 16 variants isolated from Indian Breast cancer patients showed difference in genetic diversity with that of cervical cancer isolates. AB - The genetic variations of HPV16 in Breast Cancer (BC) are not well studied unlike HPV16 in Cervical Cancer (CACX). In this study, the genetic variations of HPV16 in BC were compared with HPV16 in CACX. In sequencing analysis of LCR, E6 and E7 regions of HPV16 in BC and CACX the A lineage was seen to be 64.2% and 66.6% respectively. The other lineages showed differential frequency in BC and CACX. The mutation frequency index of the regions in BC and CACX was in the following order: LCR>E6>E7. However, the inter-patient genetic diversity in LCR and E6/E7 regions was high in BC than CACX. The LCR region showed more variations than the E6/E7 region in BC. Apart from some common variations, some unique tissue specific variants in LCR and E6/E7 region were seen in BC and in CACX. Besides the selection of some common variants in both BC and CACX, some unique variants in BC (D98Y; 395 G>T) and CACX (R48W; 245 G>T) were observed. The 7521 G>A variant of LCR showed association with Luminal B subtype of BC and progression of CACX. Whereas, 145 G>T (Q14H) and 335 C>T (H78Y) variants of E6 showed association with either early invasiveness of BC and/or poor outcome of the patients. Thus, this study indicates that there may be a difference in the genetic variation of HPV16 in BC and in CACX. PMID- 28988983 TI - Molecular characterization of two badnavirus genomes associated with Canna yellow mottle disease. AB - Members of the genus Badnavirus have a single non-covalently closed circular double-stranded DNA genome of 7.2-9.2kb. The genome encodes three open reading frames (ORFs) on the positive DNA strand. Canna yellow mottle virus (CaYMV) is a badnavirus that has been described as the etiological cause of yellow mottle disease in canna, although only a 565bp fragment of the genome has been previously reported from cannas. In this report, concentrated virions were recovered from infected canna plants and nucleic acids were extracted. Two full length sequences represent two badnavirus genomes were recovered and were determined to be 6966bp and 7385bp in length. These DNAs represent a virus strain belonging to Canna yellow mottle virus and a novel species tentatively termed Canna yellow mottle associated virus. Phylogenetic analysis indicates that these two viruses are closely related to sugarcane bacilliform GD virus, pineapple bacilliform comosus virus, banana streak MY virus, and cycad leaf necrosis virus. We also showed naturally grown canna plants to be frequently co-infected by these two badnaviruses along with a potyvirus, Canna yellow streak virus. PMID- 28988984 TI - Prevention of chronic renal allograft rejection by AS2553627, a novel JAK inhibitor, in a rat transplantation model. AB - BACKGROUND: Janus kinase (JAK) inhibitors are thought to be promising candidates to aid renal transplantation. However, the effectiveness of JAK inhibitors against features of chronic rejection, including interstitial fibrosis/tubular atrophy (IF/TA) and glomerulosclerosis, has not been elucidated. Here, we investigated the effect of AS2553627, a novel JAK inhibitor, on the development of chronic rejection in rat renal transplantation. METHODS: Lewis (LEW) to Brown Norway (BN) rat renal transplantation was performed. Tacrolimus (TAC) at 0.1mg/kg was administered intramuscularly once a day for 10 consecutive days starting on the day of transplantation (days 0 to 9) to prevent initial acute rejection. After discontinuation of TAC treatment from days 10 to 28, AS2553627 (1 and 10mg/kg) was orally administered with TAC. At 13weeks after renal transplantation, grafts were harvested for histopathological and mRNA analysis. Creatinine and donor-specific antibodies were measured from plasma samples. Urinary protein and kidney injury markers were also evaluated. RESULTS: AS2553627 in combination with TAC exhibited low plasma creatinine and a marked decrease in urinary protein and kidney injury markers, such as tissue inhibitor of metalloproteinase-1 and kidney injury molecule-1. At 13weeks, histopathological analysis revealed that AS2553627 treatment inhibited glomerulosclerosis and IF/TA. In addition, upregulation of cell surface markers, fibrosis/epithelial mesenchymal transition and inflammation-related genes were reduced by the combination of AS2553672 and TAC, particularly CD8 and IL-6 mRNAs, indicating that AS2553627 prevented cell infiltration and inflammation in renal allografts. CONCLUSIONS: These results indicate the therapeutic potential of JAK inhibitors in chronic rejection progression, and suggest that AS2553627 is a promising agent to improve long-term graft survival after renal transplantation. PMID- 28988985 TI - FACS-Assisted CRISPR-Cas9 Genome Editing Facilitates Parkinson's Disease Modeling. AB - Genome editing and human induced pluripotent stem cells hold great promise for the development of isogenic disease models and the correction of disease associated mutations for isogenic tissue therapy. CRISPR-Cas9 has emerged as a versatile and simple tool for engineering human cells for such purposes. However, the current protocols to derive genome-edited lines require the screening of a great number of clones to obtain one free of random integration or on-locus non homologous end joining (NHEJ)-containing alleles. Here, we describe an efficient method to derive biallelic genome-edited populations by the use of fluorescent markers. We call this technique FACS-assisted CRISPR-Cas9 editing (FACE). FACE allows the derivation of correctly edited polyclones carrying a positive selection fluorescent module and the exclusion of non-edited, random integrations and on-target allele NHEJ-containing cells. We derived a set of isogenic lines containing Parkinson's-disease-associated mutations in alpha-synuclein and present their comparative phenotypes. PMID- 28988986 TI - Phosphorylation of Threonine343 Is Crucial for OCT4 Interaction with SOX2 in the Maintenance of Mouse Embryonic Stem Cell Pluripotency. AB - OCT4 is required to maintain the pluripotency of embryonic stem cells (ESCs); yet, overdose-expression of OCT4 induces ESC differentiation toward primitive endoderm. The molecular mechanism underlying this differentiation switch is not fully understood. Here, we found that substitution of threonine343 by alanine (T343A), but not aspartic acid (T343D), caused a significant loss of OCT4 phosphorylation signal in ESCs. Loss of such OCT4-phosphorylation compromises its interaction with SOX2 but promotes interaction with SOX17. We therefore propose that threonine343-based OCT4-phosphorylation is crucial for the maintenance of ESC pluripotency. This OCT4-phosphorylation-based mechanism may provide insight into the regulation of lineage specification during early embryonic development. PMID- 28988987 TI - A DGCR8-Independent Stable MicroRNA Expression Strategy Reveals Important Functions of miR-290 and miR-183-182 Families in Mouse Embryonic Stem Cells. AB - Dgcr8 knockout cells provide a great means to understand the function of microRNAs (miRNAs) in vitro and in vivo. Current strategies to study miRNA function in Dgcr8 knockout cells depend on transient transfection of chemically synthesized miRNA mimics, which is costly and not suitable for long-term study and genetic selection of miRNA function. Here, we developed a cost-effective DGCR8-independent stable miRNA expression (DISME) strategy based on a short hairpin RNA vector that can be precisely processed by DICER. Using DISME, we found that miR-294 promoted the formation of meso-endoderm lineages during embryonic stem cell differentiation. Furthermore, DISME allowed for a pooled screen of miRNA function and identified an miR-183-182 cluster of miRNAs promoting self-renewal and pluripotency in mouse embryonic stem cells. Altogether, our study demonstrates that DISME is a robust and cost-effective strategy that allows for long-term study and genetic selection of miRNA function in a Dgcr8 knockout background. PMID- 28988988 TI - Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Encapsulating Bioactive Hydrogels Improve Rat Heart Function Post Myocardial Infarction. AB - Tissue engineering offers an exciting possibility for cardiac repair post myocardial infarction. We assessed the effects of combined polyethylene glycol hydrogel (PEG), human induced pluripotent stem cell-derived cardiomyocyte (iPSC CM), and erythropoietin (EPO) therapy in a rat model of myocardial infarction. PEG with/out iPSC-CMs and EPO; iPSC-CMs in saline; or saline alone was injected into infarcted hearts shortly after infarction. Injection of almost any combination of the therapeutics limited acute elevations in chamber volumes. After 10 weeks, attenuation of ventricular remodeling was identified in all groups that received PEG injections, while ejection fractions were significantly increased in the gel-EPO, cell, and gel-cell-EPO groups. In all treatment groups, infarct thickness was increased and regions of muscle were identified within the scar. However, no grafted cells were detected. Hence, iPSC-CM-encapsulating bioactive hydrogel therapy can improve cardiac function post myocardial infarction and increase infarct thickness and muscle content despite a lack of sustained donor-cell engraftment. PMID- 28988989 TI - FUS Mutant Human Motoneurons Display Altered Transcriptome and microRNA Pathways with Implications for ALS Pathogenesis. AB - The FUS gene has been linked to amyotrophic lateral sclerosis (ALS). FUS is a ubiquitous RNA-binding protein, and the mechanisms leading to selective motoneuron loss downstream of ALS-linked mutations are largely unknown. We report the transcriptome analysis of human purified motoneurons, obtained from FUS wild type or mutant isogenic induced pluripotent stem cells (iPSCs). Gene ontology analysis of differentially expressed genes identified significant enrichment of pathways previously associated to sporadic ALS and other neurological diseases. Several microRNAs (miRNAs) were also deregulated in FUS mutant motoneurons, including miR-375, involved in motoneuron survival. We report that relevant targets of miR-375, including the neural RNA-binding protein ELAVL4 and apoptotic factors, are aberrantly increased in FUS mutant motoneurons. Characterization of transcriptome changes in the cell type primarily affected by the disease contributes to the definition of the pathogenic mechanisms of FUS-linked ALS. PMID- 28988990 TI - Efficient Large-Scale 2D Culture System for Human Induced Pluripotent Stem Cells and Differentiated Cardiomyocytes. AB - Cardiac regenerative therapies utilizing human induced pluripotent stem cells (hiPSCs) are hampered by ineffective large-scale culture. hiPSCs were cultured in multilayer culture plates (CPs) with active gas ventilation (AGV), resulting in stable proliferation and pluripotency. Seeding of 1 * 106 hiPSCs per layer yielded 7.2 * 108 hiPSCs in 4-layer CPs and 1.7 * 109 hiPSCs in 10-layer CPs with pluripotency. hiPSCs were sequentially differentiated into cardiomyocytes (CMs) in a two-dimensional (2D) differentiation protocol. The efficiency of cardiac differentiation using 10-layer CPs with AGV was 66%-87%. Approximately 6.2-7.0 * 108 cells (4-layer) and 1.5-2.8 * 109 cells (10-layer) were obtained with AGV. After metabolic purification with glucose- and glutamine-depleted and lactate supplemented media, a massive amount of purified CMs was prepared. Here, we present a scalable 2D culture system using multilayer CPs with AGV for hiPSC derived CMs, which will facilitate clinical applications for severe heart failure in the near future. PMID- 28988991 TI - Bifunctional Hydrogels Containing the Laminin Motif IKVAV Promote Neurogenesis. AB - Engineering of biomaterials with specific biological properties has gained momentum as a means to control stem cell behavior. Here, we address the effect of bifunctionalized hydrogels comprising polylysine (PL) and a 19-mer peptide containing the laminin motif IKVAV (IKVAV) on embryonic and adult neuronal progenitor cells under different stiffness regimes. Neuronal differentiation of embryonic and adult neural progenitors was accelerated by adjusting the gel stiffness to 2 kPa and 20 kPa, respectively. While gels containing IKVAV or PL alone failed to support long-term cell adhesion, in bifunctional gels, IKVAV synergized with PL to promote differentiation and formation of focal adhesions containing beta1-integrin in embryonic cortical neurons. Furthermore, in adult neural stem cell culture, bifunctionalized gels promoted neurogenesis via the expansion of neurogenic clones. These data highlight the potential of synthetic matrices to steer stem and progenitor cell behavior via defined mechano-adhesive properties. PMID- 28988992 TI - Limb-Leaf designs for adaptive exploration of the dose-response curve. AB - We propose a two-stage strategy, called the Limb-Leaf method, to explore the dose response curve using dose promotion and addition in the context of adaptive seamless Phase II/III trials. Strong control of the overall type 1 familywise error rate of the proposed method is enforced by the closed testing principle. The design constants are determined to minimize the risk-adjusted expected total sample size while maintaining a target power. In the case of a nonmonotonic dose response curve where more doses are required to adequately explore the curve, substantial savings in sample size are achieved compared with a traditional strategy which offers only selection and promotion from among initial first stage doses. PMID- 28988993 TI - Characterization and functional assessment of the NLRC3-like molecule of the goldfish (Carassius auratus L.). AB - The NLRC3-like (NLRC3L) molecule from the goldfish transcriptome database was identified and characterized. Quantitative gene expression analysis revealed the highest mRNA levels of NLRC3L were in the spleen and intestine, with lower mRNA levels observed in muscle and liver. Goldfish NLRC3L was differentially expressed in goldfish immune cell populations with highest mRNA levels measured in PBLs and macrophages. We generated a recombinant form of the molecule (rgfNLRC3L) and an anti-CT-NLRC3L IgG. Treatment of goldfish primary kidney macrophages in vitro with ATP, LPS and heat-killed Aeromonas salmonicida up-regulated the NLRC3L mRNA and protein. Confocal microscopy and co-immunoprecipitation assays indicated that goldfish rgfNLRC3L interacted with apoptosis-associated spec-like protein (ASC) in eukaryotic cells, indicating that NLRC3L may participate in the regulation of the inflammasome responses. The dual-luciferase reporter assay showed that NLRC3L over-expression did not cause the activation of NF-kappaB, but that it cooperated with RIP2 to down-regulate NF-kappaB activation. Our results indicate that the NLRC3L may function as a regulator of NLR pathways in teleosts. PMID- 28988994 TI - Locked nucleic acid: modality, diversity, and drug discovery. AB - Over the past 20 years, the field of RNA-targeted therapeutics has advanced based on discoveries of modified oligonucleotide chemistries, and an ever-increasing understanding of how to apply cellular assays to identify oligonucleotides with improved pharmacological properties in vivo. Locked nucleic acid (LNA), which exhibits high binding affinity and potency, is widely used for this purpose. Our understanding of RNA biology has also expanded tremendously, resulting in new approaches to engage RNA as a therapeutic target. Recent observations indicate that each oligonucleotide is a unique entity, and small structural differences between oligonucleotides can often lead to substantial differences in their pharmacological properties. Here, we outline new principles for drug discovery exploiting oligonucleotide diversity to identify rare molecules with unique pharmacological properties. PMID- 28988995 TI - Overcoming or circumventing the stratum corneum barrier for efficient transcutaneous immunization. AB - Transcutaneous immunization (TCI) is a promising alternative to vaccine delivery via the subcutaneous and intramuscular routes because of the unique immunological characteristics of the skin. However, the stratum corneum (SC) prevents entry of most therapeutic compounds into the body. Several physical devices have been developed to overcome the SC barrier, but still damage the skin. However, by targeting antigens to the abundant perifollicular antigen-presenting cells (APCs), the transfollicular route might be a promising approach for TCI without compromising the skin barrier. PMID- 28988996 TI - 2017: beginning of a new era for Chlamydia research in China and the rest of the world. AB - The First Chinese Chlamydia Research Meeting was held in Lanzhou, China in May 2017, 60 years after the disclosure of reproducible isolation of Chlamydia trachomatis by (Fei-fan Tang). We report current state of the Chlamydia research community in China, and briefly review recent progress in Chlamydia vaccinology. The meeting represents a new milestone for Chlamydia research in the country. The Chinese Chlamydia Research Society (CCRS) was formed during the meeting. Future meetings will be held biennially and should facilitate collaboration of Chinese researchers with their domestic and international colleagues. PMID- 28988997 TI - Offering smoking treatment to primary care patients in two Wisconsin healthcare systems: Who chooses smoking reduction versus cessation? AB - Smokers unwilling to make a quit attempt can still benefit from smoking intervention. However, it is unclear what proportion of smokers will enter such a Motivation phase intervention, and whether such an intervention attracts different types of smokers than does abstinence oriented treatment. We conducted a study from June 2010 to October 2013 based on a chronic care model of tobacco treatment among study eligible primary care patients (N=1579; 58% women, 89% White) presenting for regular health care visits in southern Wisconsin, U.S. Medical assistants, prompted via the electronic health record (EHR), invited smokers (n=10,242) to learn more about treatment options to help them either reduce their smoking or quit. Of those invited to learn more who were then reached by study staff, 10.2% (n=1046) reported interest in reduction treatment and 24% (n=2465) reported interest in cessation treatment. Patients who selected and ultimately entered reduction (n=492) versus cessation (n=1087) were more likely to report: older age; a history of anxiety; lower motivation to quit; lower primary dependence motives; more close friends or family who smoke; and a greater interval since their last quit attempt. Results suggest that Motivation phase treatment aimed at smoking reduction may increase the proportion and range of smokers inducted into tobacco treatment. PMID- 28988998 TI - Noncommunicable Disease Risk Factors in Developing Countries: Policy Perspectives. PMID- 28988999 TI - Of weekend warriors and couch potatoes: Socio-economic determinants of physical activity in Swiss middle-aged adults. AB - Determinants of the interplay between physical activity (PA) and sedentary (SE) status are poorly known. We assessed the socio-economic determinants of PA and SE behaviours and patterns in a population-based study (The CoLaus study, Lausanne, Switzerland, 2014-2017). 2229 adults (51.8% women, age range 45-86 years) had PA and SE levels measured for 14 days using a wrist-worn accelerometer. Four activity behaviours: (1) 'Couch potato': low PA & high SE; (2) 'Light mover': low PA & low SE; (3) 'Sedentary exerciser': high PA & high SE, and (4) 'Busy bee': high PA & low SE; and three activity patterns: (1) 'Inactive', (2) 'Weekend warrior', and (3) 'Regularly active' were defined. Employment, household income and educational level were collected by questionnaire. For activity behaviours, relative to 'Couch potatoes', multivariate analysis showed that being employed and having a low educational level were positively associated with 'Light movers': relative risk ratios and (95% confidence interval): 1.54 (1.00-2.37) and 1.73 (1.11-2.69), respectively, and also with 'Busy bees': 1.49 (1.09-2.04) and 1.71 (1.26-2.32), respectively. High household income was negatively associated with 'Light movers': 0.58 (0.34-0.97) and positively with 'Sedentary exercisers': 1.85 (1.10-3.10). For activity patterns, relative to 'Inactives', being employed and having a high household income were positively associated with 'Weekend warriors': 1.78 (1.26-2.50) and 1.59 (1.07-2.36), respectively, while having a low educational level was positively associated with 'Regularly actives': 1.76 (1.32-2.34). Employment, educational level and household income are significantly but differently associated with activity behaviours and patterns. PMID- 28989000 TI - Use of 18F-FDG PET-CT imaging to determine internal mammary lymph node location for radiation therapy treatment planning in breast cancer patients. AB - PURPOSE: Adjuvant internal mammary lymph node (IMN) radiation is often delivered with 2-dimensional techniques that use anatomic landmarks and predetermined depths for field placement and dose specification. In contrast, 3-dimensional planning uses the internal mammary vessels (IMVs) to localize the IMNs for planning. Our purpose was to determine if localization of the involved IMN (i IMN) by 18F-labeled fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) offers opportunities to improve treatment. METHODS AND MATERIALS: Breast cancer patients (n = 80) who had i-IMNs (n = 112) on PET-CT for initial staging (n = 40) or recurrence (n = 40) were studied. Size, intercostal space (IC), and distance from skin, sternum, and IMVs were recorded. Effects on 2- and 3-dimensional planning were evaluated. RESULTS: Most i-IMNs (94.6%) were in the first to third ICs. Few were in the fourth (4.5%) or fifth (0.9%) IC. Mean i-IMN depth was 3.4 cm (range, 1.1-7.3 cm). Prescriptive depths of 4, 5, and 6 cm would result in undertreatment of 25%, 10.7%, and 5.3% of IMNs, respectively. Most IMNs (86.6%) were lateral or adjacent to the sternal edge. Only 13.4% of IMNs were posterior to the sternum. Use of the ipsilateral or contralateral sternal edge for field placement increases the risk of geographic miss or excess normal tissue exposure. Most i-IMNs were adjacent to (83%) or <=0.5 cm (14%) from the IMV edge. Three (3%) were >0.5 cm beyond the IMV edge. The clinical target volume (CTV) defined by the first to third ICs encompassed 78% of i-IMNs. IMN-CTV coverage of i-IMNs increased with inclusion of the fourth IC (82%), 0.5 cm medial and lateral margin expansion (93%), or both (96.5%). CONCLUSION: Two-dimensional treatment techniques risk geographic miss of IMNs and exposure of excess normal tissue to radiation. An IMN-CTV defined by the IMVs from the first to third ICs with 0.5-cm medial and lateral margin expansion encompasses almost all i-IMNs identified on PET-CT imaging. Inclusion of the fourth IC offers modest coverage improvement, and its inclusion should be weighed against potential increase in cardiac exposure. SUMMARY: The use of 2-dimensional treatment techniques for adjuvant internal mammary lymph node (IMN) radiation may cause geographic miss of tumor and expose normal tissue to radiation injury. Conformal 3-dimensional planning improves coverage and reduces risk of normal tissue damage by using the internal mammary vessel to define an IMN clinical target volume (CTV). Contouring the IMN-CTV from the first to third intercostal spaces with a 0.5-cm expansion medially and laterally encompasses most IMN. Positron emission tomography-computed tomography may have a role in radiation planning by identifying involved-IMN for dose escalation. PMID- 28989001 TI - HPV-related nasopharyngeal and cervical cancer in a married couple in North America. PMID- 28989002 TI - CHI3L1 and CHI3L2 overexpression in motor cortex and spinal cord of sALS patients. AB - BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a rapidly progressive neurodegenerative disease characterized by the degeneration and death of upper (UMN) and lower (LMN) motor neurons. In the last decade, it has been shown that Chitinases are an important prognostic indicator of neuro-inflammatory damage induced by microglia and astrocytes. MATERIALS AND METHODS: We analyzed microarray datasets obtained from the Array Express in order to verify the expression levels of CHI3L1 and CHI3L2 in motor cortex biopsies of sALS patients with different survival times. We also divided the sALS patients into smokers and non-smokers. In order to extend our analysis, we explored two additional microarray datasets, GSE833 and GSE26927, of post-mortem spinal cord biopsies from sALS patients. RESULTS: The analysis showed that CHI3L1 and CHI3L2 expression levels were significantly upregulated in the motor cortex of sALS patients, compared to the healthy controls. Moreover, their expression levels were negatively correlated with survival time. Interesting results were obtained when we compared the expression levels of Chitinases among smokers. We showed that CHI3L1 and CHI3L2 were significantly upregulated in sALS smokers compared to non-smokers. Furthermore, we found that four genes belonging to the Chitinases network (SERPINA3, C1s, RRAD, HLA-DQA1) were significantly upregulated in the motor cortex of sALS patients and positively correlated with Chitinases expression levels. Similar results were obtained during the exploration of the two-microarray dataset. CONCLUSIONS: This study suggests that CHI3L1 and CHI3L2 are associated with the progression of neurodegeneration in motor cortex and spinal cord of sALS patients. PMID- 28989003 TI - A novel approach to the endoscopic removal of a hollow fragile foreign body from the rectum. PMID- 28989004 TI - Per-oral endoscopic myotomy in achalasia with large esophageal diverticulum: the "owl eyes" sign. PMID- 28989005 TI - Postmucosectomy colonic pseudoperforation. PMID- 28989006 TI - Comparison of endoscopy and radiographic imaging for detection of esophageal inflammation and remodeling in adults with eosinophilic esophagitis. AB - BACKGROUND AND AIMS: Eosinophil predominant mucosal inflammation is central to the diagnosis and activity assessment of eosinophilic esophagitis (EoE). Esophageal mural remodeling is an important consequence of EoE that is responsible for adverse events of dysphagia, food impaction, and esophageal stenosis. The aim of this study was to compare upper endoscopy (EGD) with barium upper GI study (UGI) for the detection of esophageal inflammation and remodeling in adults with EoE. METHODS: A retrospective review on a single-center database of adults with confirmed EoE identified those with EGD and UGI performed within 6 months of each another. Studies were reviewed for mucosal inflammatory and remodeling abnormalities. RESULTS: Seventy patients were included. Initial UGI results were consistent with EoE in 10% and suggestive of EoE in 39%. Review of UGI by a senior GI radiologist increased detection of changes consistent with EoE (34%). EGD identified characteristic abnormalities in 93%, which was significantly greater than UGI (67%). Inflammatory features were more frequently appreciated on EGD (74%) compared with UGI (21%). There was no significant difference in fibrostenotic changes observed on EGD (84%) versus UGI (73%). CONCLUSIONS: EGD and UGI have similar sensitivity for identifying the remodeling consequences of EoE; however, inflammatory features are better assessed on EGD. Inadequate sensitivity of UGI for composite features of EoE limits its capabilities as a diagnostic test, although radiologists' awareness significantly increases the diagnostic yield of UGI. UGI and EGD may identify fibrostenotic changes unappreciated by its counterpart and thus provide complementary information in select patients. PMID- 28989007 TI - Endoscopic reconstruction of Roux-en-Y gastric bypass with placement of gastrojejunal and remnant-jejunal lumen-apposing metal stents. PMID- 28989008 TI - Metastatic melanoma in the ampulla of Vater. PMID- 28989009 TI - The Surgery Innovation and Entrepreneurship Development Program (SIEDP): An Experiential Learning Program for Surgery Faculty to Ideate and Implement Innovations in Health care. AB - OBJECTIVE: Surgeons are continually engaged in the incorporation of new technologies in their practice. In the operating room and beyond, they combine technical skill with creative problem solving to improve tools and techniques for patient care, making them natural innovators. However, despite their innovative tendencies, education on entrepreneurship and commercialization is severely lacking. Moreover, with increasing pressure to meet productivity metrics, their availability to learn the complexities of commercialization is limited. To address these challenges, we designed the Surgery Innovation and Entrepreneurship Development Program (SIEDP) with the objective to advance faculty innovations, develop new departmental innovation initiatives, and improve faculty education in the area of innovation, entrepreneurship, and commercialization. DESIGN: The SIEDP is a first-of-its-kind experiential learning program specifically designed for busy clinical and research faculty in a major academic surgery department. Participants ideated and formed teams around health care innovations as they progressed through a 9-month curriculum of expert guest lectures and interactive workshops. A postprogram evaluation and outcome tracking method was used to evaluate attainment of educational objectives and project development milestones. SETTING: The Department of Surgery, University of Michigan Medical School, Ann Arbor, Michigan. PARTICIPANTS: Eleven surgery faculty of varying academic rank and surgical subspecialties. RESULTS: The program generated 2 faculty startup companies, 1 departmental commercial product, 3 patent disclosures, and 3 innovations that received additional funding. All participants in the program reported a significant increase in their understanding of innovation and entrepreneurship and that participation was a worthwhile faculty development activity. CONCLUSION: Despite the various challenges and time constraints of surgical practices, programs like SIEDP can educate surgeons and other academicians on innovation, entrepreneurship, and commercialization and add value to the academic mission of providing excellent education, research, and clinical care. PMID- 28989010 TI - Global Health Education for Medical Students: When Learning Objectives Include Research. AB - BACKGROUND: The Luke Commission, a provider of comprehensive mobile health outreach in rural Swaziland, focuses on human immunodeficiency virus testing and prevention, including the performance of over 100 circumcisions weekly. Educational objectives for medical student global health electives are essential. Learning research methodology while engaging in clinical activities reinforces curriculum goals. Medical care databases can produce clinically significant findings affecting international health policy. Engaging in academic research exponentially increased the educational value of student experiences during an international medical elective. METHODS: Staff of the Luke Commission, a nongovernmental organization, collected and deidentified information from 1500 Swazi male patients undergoing circumcision from January through June of 2014. Medical students designed studies and analyzed these data to produce research projects on adverse event rates, pain perception, and penile malformations. Institutional review board approval was obtained from the home institution and accompanying senior surgical faculty provided mentorship. RESULTS: First-year medical students enrolled in an international medical elective to explore resource availability, cultural awareness, health care provision, and developing world endemic diseases. While in country, students learned research methodology, collected data, and engaged in research projects. Following the trip, students presented posters at over 10 regional and national meetings. All 4 articles are accepted or under consideration for publication by major journals. CONCLUSIONS: During international medical electives the combination of clinical experiences and access to databases from health aid organizations provides the foundation for productive medical student research. All participants benefit from the relationships formed by aid organizations, medical students, and patient populations. Global health research has many complexities, but through careful planning and cultural awareness, medical students can increase their research skills and contribute to the medical literature, bringing attention to and improving health care policies around the world. In sum, the educational experience of medical students is enhanced through the interaction of delivering patient care and completing clinical research studies. PMID- 28989011 TI - Isoflavonoids as wound healing agents from Ononidis Radix. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Dried roots of Ononis spinosa L. are traditionally used for their diuretic, anti-inflammatory and wound healing effects. AIM OF THE STUDY: Isolation of the bioactive compounds of Ononis spinosa L. subsp. leiosperma (Boiss.) Sirj. MATERIALS AND METHODS: Ethyl acetate extract prepared from the roots of Ononis spinosa L. subsp. leiosperma (Boiss.) Sirj. was subjected to silica gel column. The fractions were tested for their wound healing and anti-inflammatory activities. Linear incision and circular excision wound models and hydroxypyroline estimation assay were used for the wound healing activity. Carrageenan-induced hind paw edema, TPA-induced ear edema and acetic acid-induced increase in capillary permeability tests as acute inflammation; FCA induced arthritis as chronic inflammation models were used for the assessment of anti-inflammatory activity. Antioxidant capacities of the fractions were tested using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, 2,2-azino bis-(3-ethylbenzthiazoline-6-sulfonic acid (ABTS) scavenging activity assay, reducing power assay and hydroxyl radical (OH-) scavenging assay. The isolation procedure was continued with the active fraction (Fr-E5). RESULTS: Fr-E5 exhibited remarkable wound healing activity with the 33.4% tensile strength value on the linear incision wound model and 51.4% reduction of the wound area at the day 12 on the circular excision wound model. Hydroxyproline content of the tissue treated by Fr-E5 was found to be 30.9 +/- 0.72MUg/mg. Acetic acid induced increase in capillary permeability test results revealed that Fr-E5 inhibited inflammation by the value of 40.3%. Fr-E5 showed 28.1-32.2% inhibition in carrageenan-induced hind paw edema test while did not possess activity on TPA induced ear edema and FCA-induced arthritis models. Trifolirhizin, ononin, medicarpin-3-O-glucoside, onogenin-7-O-glucoside and sativanone-7-O-glucoside were isolated from Fr-E5 and tested for their wound healing activities using by measuring their inhibition of hyaluronidase, collagenase and elastase enzymes. Ononin and sativanone-7-O-glucoside inhibited hyaluronidase and elastase enzymes by 31.66% and 41.75%; 45.58% and 46.88% values respectively at the dose of 100MUg/mL. CONCLUSION: Among five isolated compounds, ononin and sativanone-7-O glucoside were found to inhibit hyaluronidase and elastase enzymes. According to the results, these compounds may majorly be responsible for the wound healing activity of the extract. PMID- 28989012 TI - In Vivo Transgene Expression in the Pancreas by the Intraductal Injection of Naked Plasmid DNA. AB - Patients with type I diabetes, which is caused by the destruction of pancreatic islets, now require regular therapeutic injections of insulin. The use of transgene therapy represents an alternate and potent strategy for the treatment of type I diabetes. However, only a limited number of studies regarding in vivo gene delivery targeting the pancreas and islets have been reported. Here, we report on the possibility of in vivo transgene expression in the pancreas by the intraductal injection of naked plasmid DNA (pDNA). Gene expression activities were detected in the pancreas of mice after the injection of naked pDNA encoding luciferase into the common bile duct. We then investigated the effects of injection dose, volume, and speed on gene delivery and determined the optimal conditions for the delivery of pDNA to the pancreas. Exogenous luciferase mRNA was detected in the pancreatic islets by reverse transcription PCR analysis. Moreover, no injury was detected in the liver, the common bile duct, or the pancreas over time after the injection. These findings indicate that the intraductal injection of naked pDNA promises to be a useful technique for in vivo gene delivery targeted to pancreatic tissue and islets. PMID- 28989013 TI - Development of a Modified-Release Formulation of Lovastatin Targeted to Intestinal Methanogens Implicated in Irritable Bowel Syndrome With Constipation. AB - There is growing evidence that methane production, predominantly by Methanobrevibacter smithii, in the intestines is a cause of constipation, pain, and bloating in irritable bowel syndrome with constipation (IBS-C). M smithii resides primarily in the large intestine but can also colonize the small intestine. In vitro studies found that the prodrug lactone form of lovastatin, found in cholesterol-lowering drugs, inhibited methane production in stool samples from patients with IBS-C. However, the cholesterol-lowering lovastatin beta-hydroxyacid was ineffective at inhibiting methane production in this system. A considerable amount of lovastatin is converted to hydroxyacid in the stomach and is absorbed. It was hypothesized that galenic innovations could protect lovastatin from the stomach and allow release in 2 strategic locations, the duodenum and the ileocecal region, to reach M smithii. The desired release profile was achieved by developing an oral dosage form containing lovastatin and coated with 2 different enteric polymers that enabled a pH-dependent "dual pulse" drug release. Combinations of the 2 coated tablets were encapsulated together to deliver the desired amount of lovastatin to the targeted intestinal locations. The capsules have been tested in vitro and in vivo and show promise in treating IBS-C. PMID- 28989014 TI - Coamorphous Active Pharmaceutical Ingredient-Small Molecule Mixtures: Considerations in the Choice of Coformers for Enhancing Dissolution and Oral Bioavailability. AB - In the recent years, coamorphous systems, containing an active pharmaceutical ingredient (API) and a small molecule coformer have appeared as alternatives to the use of either amorphous solid dispersions containing polymer or cocrystals of API and small molecule coformers, to improve the dissolution and oral bioavailability of poorly soluble crystalline API. This Commentary article considers the relative properties of amorphous solid dispersions and coamorphous systems in terms of methods of preparation; miscibility; glass transition temperature; physical stability; hygroscopicity; and aqueous dissolution. It also considers important questions concerning the fundamental criteria to be used for the proper selection of a small molecule coformer regarding its ability to form either coamorphous or cocrystal systems. Finally, we consider various aspects of product development that are specifically associated with the formulation of commercial coamorphous systems as solid oral dosage forms. These include coformer selection; screening; methods of preparation; preformulation; physical stability; bioavailability; and final formulation. Through such an analysis of coamorphous API-small molecule coformer systems, against the more widely studied API-polymer dispersions and cocrystals, it is believed that the strengths and weaknesses of coamorphous systems can be better understood, leading to more efficient formulation and manufacture of such systems for enhancing oral bioavailability. PMID- 28989015 TI - The Use of a 2,2'-Azobis (2-Amidinopropane) Dihydrochloride Stress Model as an Indicator of Oxidation Susceptibility for Monoclonal Antibodies. AB - Protein oxidation is a major pathway for degradation of biologic drug products. Past literature reports have suggested that 2,2-azobis (2-amidinopropane) dihydrochloride (AAPH), a free radical generator that produces alkoxyl and alkyl peroxyl radicals, is a useful model reagent stress for assessing the oxidative susceptibility of proteins. Here, we expand the applications of the AAPH model by pairing it with a rapid peptide map method to enable site-specific studies of oxidative susceptibility of monoclonal antibodies and their derivatives for comparison between formats, the evaluation of formulation components, and comparisons across the stress models. Comparing the free radical-induced oxidation model by AAPH with a light-induced oxidation model suggests that light sensitive residues represent a subset of AAPH-sensitive residues and therefore AAPH can be used as a preliminary screen to highlight molecules that need further assessment by light models. In sum, these studies demonstrate that AAPH stress can be used in multiple ways to evaluate labile residues and oxidation sensitivity as it pertains to developability and manufacturability. PMID- 28989016 TI - Solubilization of a Poorly Soluble B-Raf (Rapidly Accelerated Fibrosarcoma) Inhibitor: From Theory to Application. AB - The oral bioavailability of a drug candidate is influenced by its permeability, metabolism, and physicochemical properties. Among the physicochemical properties, solubility and dissolution rate often are the most critical factors affecting the oral bioavailability of a compound. The increasing challenge for the pharmaceutical industry is to achieve reasonable oral bioavailability of poorly water-soluble drug candidates. G-F is a potent and selective B-Raf (rapidly accelerated fibrosarcoma) inhibitor with poor water solubility and moderate permeability, which resulted in an absorption-limited exposure in preclinical safety studies. The intrinsic solubility of G-F is 8 MUg/mL (i.e., 0.0188 nM). In this study, pH adjustment combined with cosolvency, micellization, or complexation was applied as a technique to enhance the solubility of G-F. pH 9.5 and 4 buffers were selected to combine with the solubilization agents based on G F's acidic pKa of 7.47. The solubilization power of each solubilization agent was determined based on the experimental data. The solubility G-F can be increased up to 4000-fold in a selected combination. The advantage of combination over individual solubilization agent was demonstrated. In this study, the understanding of the solubilization power of each solubilization agent played an important role in the formulation development of this development candidate. PMID- 28989017 TI - Mechanistic Basis of Cocrystal Dissolution Advantage. AB - Current interest in cocrystal development resides in the advantages that the cocrystal may have in solubility and dissolution compared with the parent drug. This work provides a mechanistic analysis and comparison of the dissolution behavior of carbamazepine (CBZ) and its 2 cocrystals, carbamazepine-saccharin (CBZ-SAC) and carbamazepine-salicylic acid (CBZ-SLC) under the influence of pH and micellar solubilization. A simple mathematical equation is derived based on the mass transport analyses to describe the dissolution advantage of cocrystals. The dissolution advantage is the ratio of the cocrystal flux to drug flux and is defined as the solubility advantage (cocrystal to drug solubility ratio) times the diffusivity advantage (cocrystal to drug diffusivity ratio). In this work, the effective diffusivity of CBZ in the presence of surfactant was determined to be different and less than those of the cocrystals. The higher effective diffusivity of drug from the dissolved cocrystals, the diffusivity advantage, can impart a dissolution advantage to cocrystals with lower solubility than the parent drug while still maintaining thermodynamic stability. Dissolution conditions where cocrystals can display both thermodynamic stability and a dissolution advantage can be obtained from the mass transport models, and this information is useful for both cocrystal selection and formulation development. PMID- 28989018 TI - Optimization of a Vaginal Suppository Formulation to Deliver SHetA2 as a Novel Treatment for Cervical Dysplasia. AB - Cervical dysplasia induced by the human papilloma virus unpredictably progresses to cervical cancer. Therapeutic options are invasive and affect the patient's quality of life. SHetA2 has demonstrated therapeutic efficacy against human and murine human papilloma virus-induced tumors, but its oral bioavailability is <1%. An optimized vaginal suppository formulation can deliver SHetA2 in sufficient doses to prevent cervical dysplasia. The quality by design approach was employed to optimize the suppository formulation consisting of cocoa butter as base with 5% Kolliphor and 40% SHetA2. The suppository had a content uniformity of 105.44 +/- 0.42%, melted in <8 min, and had a complete release of SHetA2 in water. Administration of the suppository to mice-achieved cervix concentrations that were significantly higher than the SHetA2 therapeutic concentration, with the maximum concentration (Cmax-cervix = 336.78 MUg/g) being more than 100-fold the therapeutic SHetA2 concentration. Furthermore, the levels of cyclin D1 protein decreased 9-fold indicating a correlation of drug concentrations with the pharmacodynamic endpoint. These proof-of-concept studies suggest that the SHetA2 optimized vaginal suppository formulation may have a potential use in the prevention of cervical dysplasia, but detailed efficacy studies are required to confirm this assumption. PMID- 28989020 TI - Development of a Novel Amorphous Agomelatine Formulation With Improved Storage Stability and Enhanced Bioavailability. AB - The present work describes the development of a novel formulation of amorphous agomelatine (AGM) that exhibits enhanced in vitro dissolution rate and bioavailability, as well as improved storage stability. AGM was loaded on a mixture of microcrystalline cellulose with a high specific surface area excipient, namely colloidal silicon dioxide, employing a wet granulation method, and the resultant AGM granules were subsequently formulated into immediate release film-coated tablets. Modulated temperature differential scanning calorimetry, hot-state light microscopy, powder X-ray diffraction, attenuated total reflectance FTIR, and micro-Raman spectroscopy revealed that the active pharmaceutical ingredient existed primarily in the amorphous state within the prepared formulations, with some crystals of polymorph I also present. Accelerated stability studies for up to 6 months in alu-alu blisters showed good physicochemical stability during storage. Finally, in vitro dissolution studies and clinical trials in healthy human volunteers showed a remarkable increase in the in vitro dissolution rate and a ~1.5-fold increase in bioavailability, respectively, compared to the marketed product. PMID- 28989019 TI - Drug-Disease Interaction: Effect of Inflammation and Nonsteroidal Anti Inflammatory Drugs on Cytochrome P450 Metabolites of Arachidonic Acid. AB - Inflammatory conditions increase cardiovascular (CV) risk. Some nonsteroidal anti inflammatory drugs (NSAIDs) that are used to treat pain and inflammation are also associated with CV complications. Inflammation, but not NSAIDs, disrupts the balance of vasodilator and vasoconstrictor components of the renin-angiotensin system within the heart. Herein, we report the effect of both inflammation and NSAIDs (rofecoxib, celecoxib, and meloxicam) on the physiologically active cytochrome P450 metabolites of arachidonic acid (ArA) in the rat with adjuvant arthritis. After oral administration of 7 daily therapeutically equivalent doses of NSAIDs or vehicle, the anti-inflammatory response, as well as the ArA metabolites and drug concentrations in plasma, heart and kidneys were assessed. Inflammation in the form of adjuvant arthritis caused a significant tissue dependent imbalance of ArA metabolites by elevating the ratio of cardiotoxic 20 hydroxyeicosatetraenoic acid over cardioprotective epoxyeicosatrienoic acids in the heart, and reducing the ratio in the kidney. The observed imbalance was augmented by cardiotoxic rofecoxib but not by other examined NSAIDs with known milder cardiotoxicity. The cardio-renal toxicity of NSAIDs with known severe CV side effects may be due to altered cytochrome P450-mediated ArA acid metabolism. The ArA metabolism profile may be a marker of NSAIDs safety and toxicity. PMID- 28989022 TI - How Sensitive Are Transdermal Transport Predictions by Microscopic Stratum Corneum Models to Geometric and Transport Parameter Input? AB - While predictive models of transdermal transport have the potential to reduce human and animal testing, microscopic stratum corneum (SC) model output is highly dependent on idealized SC geometry, transport pathway (transcellular vs. intercellular), and penetrant transport parameters (e.g., compound diffusivity in lipids). Most microscopic models are limited to a simple rectangular brick-and mortar SC geometry and do not account for variability across delivery sites, hydration levels, and populations. In addition, these models rely on transport parameters obtained from pure theory, parameter fitting to match in vivo experiments, and time-intensive diffusion experiments for each compound. In this work, we develop a microscopic finite element model that allows us to probe model sensitivity to variations in geometry, transport pathway, and hydration level. Given the dearth of experimentally-validated transport data and the wide range in theoretically-predicted transport parameters, we examine the model's response to a variety of transport parameters reported in the literature. Results show that model predictions are strongly dependent on all aforementioned variations, resulting in order-of-magnitude differences in lag times and permeabilities for distinct structure, hydration, and parameter combinations. This work demonstrates that universally predictive models cannot fully succeed without employing experimentally verified transport parameters and individualized SC structures. PMID- 28989021 TI - Enhanced Dissolution of a Porous Carrier-Containing Ternary Amorphous Solid Dispersion System Prepared by a Hot Melt Method. AB - The focus of our study was to employ a solvent-free, thermal process to evaluate the use of a porous carrier in a drug-polymer-porous carrier ternary formulation containing a high drug load (e.g., >=50% w/w). The purpose of the study was to improve the dissolution properties of the biopharmaceutical classification system class II drug, indomethacin, in the ternary formulation. The effect that the selected polymer has on properties of the formulation was studied, and the formulation characteristics of hypromellose (AF15), copovidone (VA64), and polyvinyl alcohol-polyethylene glycol graft copolymer was evaluated to understand differences in dissolution rates and drug adsorption onto the porous carrier. The ternary formulations were manufactured using a thermal technique that relied on heating and mixing, without the necessity of mechanical shear. All thermally processed granules that employed the porous carrier exhibited immediate release compared with crystalline indomethacin and physical mixtures. In addition, the ternary formulations maintained supersaturation compared with the binary formulations without polymer. The results of this study indicated that the thermally processed ternary formulations containing a porous carrier demonstrated a much improved dissolution profile in nonsink conditions. PMID- 28989023 TI - Evaluation of Glass Delamination Risk in Pharmaceutical 10 mL/10R Vials. AB - Glass delamination is characterized by the dissociation of glass flakes from the glass surface. Since glass delamination is time dependent, 5 vial types were investigated to assess delamination under accelerated stress conditions published as quick tests in literature and compared to stress testing recommended per United States Pharmacopoeia <1660>. A broad panel of analytical techniques was employed to test the solution for visible/subvisible particles and leachables and characterize topography and composition of the surface. The vial types showed significant differences in surface durability when applying the same stress conditions. An increase in glass leachables and change in topography were shown for uncoated vials. An indication for an elevated delamination risk was confirmed for Expansion 33 vials only by the compiled analytical data set including particle assessment and change in elemental composition of the near glass surface investigated by dynamic secondary ion mass spectrometry. The delamination test protocols differ in test solution, handling, and time. Before choosing the most appropriate protocol to predict delamination propensity and mimic real-time conditions, long-term storage data are needed. A combination of analytical techniques to study the risk for long-term corrosion of glass is highly recommended covering the 3 aspects: visible/subvisible particle assessment, solution analysis, and surface characterization. PMID- 28989024 TI - Protein kinase C downregulation induces senescence via FoxO3a inhibition in HCT116 and HEK293 cells. AB - We investigated the impact of protein kinase C (PKC) on cellular senescence. The PKC activity and expression of conventional PKC (cPKC) and atypical PKC (aPKC) isoforms decreased during replicative senescence in IMR-90 cells. Forced inhibition of cPKC or aPKC induced the activation of senescence markers, including senescence-associated beta-galactosidase activity and reactive oxygen species (ROS)-p53-p21Cip1/WAF1 axis in HCT116 and HEK293 cells. PKC inhibition triggered the nuclear exportation of FoxO3a via stimulation of AKT-mediated phosphorylation of FoxO3a, and thereby decreased the transcription of FoxO3a target genes. Conversely, ectopic expression of the PKC isoforms led to stimulation of the nuclear import of FoxO3a and expression of the FoxO3a target genes. Ectopic FoxO3a expression attenuated ROS accumulation and senescent phenotypes induced by PKC inhibition. Therefore, this study suggests for the first time that downregulation of PKC induces senescence through the AKT-FoxO3a ROS-p53-p21Cip1/WAF1 pathway in HCT116 and HEK293 cells. PMID- 28989025 TI - AAV-mediated conversion of human pluripotent stem cell-derived pacemaker. AB - Malfunction of nodal pacemaker (Pm) cardiomyocytes (CMs) due to diseases or aging leads to rhythm generation disorders, necessitating electronic Pm implantation. We functionally reprogrammed human pluripotent stem cell (hPSC) derived ventricular (V) CMs into -PmCMs via recombinant adeno-associated virus serotype 9 (rAAV9)-mediated overexpression of engineered HCN1 channel (HCN1DeltaDeltaDelta) whose S3-S4 linker has been strategically deleted by design to promote cardiac pacemaking. rAAV9-HCN1DeltaDeltaDelta-reprogrammed hPSC-PmCMs converted from VCMs showed automaticity and action potential parameters typical of native nodal PmCMs. Implantation of rAAV9-HCN1DeltaDeltaDelta-based BPm in a preclinical porcine model of complete heart block significantly reduced the dependence on device-supported pacing and generated spontaneous heart rhythms from the BPm. Collectively, these results have further laid the groundwork on BPm for future translation. PMID- 28989026 TI - Activation of nuclear beta-catenin/c-Myc axis promotes oxidative stress injury in streptozotocin-induced diabetic cardiomyopathy. AB - Myocardial oxidative stress injury plays a crucial role in the pathogenesis of diabetic cardiomyopathy (DCM). Wnt/beta-catenin signaling has been reported to involve in various heart diseases. However, the underlying mechanism associated with beta-catenin in DCM remains elusive. This study intended to explore the effect of beta-catenin on oxidative damage of DCM by establishing streptozotocin (STZ)-induced diabetic mouse model and hydrogen peroxide (H2O2)-treated myocardial cell model. Cardiac oxidative stress in DCM was detected by measurements of lipid peroxidation and anti-oxidative enzyme activities as well as DHE staining. Nuclear beta-catenin activity and oxidative damage degree were measured by western blotting, qPCR, MTT assay and TUNEL staining. Cardiac function and morphology were evaluated by echocardiography and histopathology. Under diabetic oxidative stress or H2O2 stimulation, nuclear beta-catenin accumulation upregulated downstream c-Myc and further facilitated DNA damage and p53-mediated apoptosis as well as cell viability reduction, followed by phenotypic changes of cardiac dysfunction, interstitial fibrosis deposition and myocardial atrophy. Conversely, through directly inhibiting nuclear beta catenin/c-Myc axis, not only did siRNA knockdown of beta-catenin or c-Myc attenuate cell injury in H2O2-stimulated cardiomyocytes, but also diabetic cardiac-specific beta-catenin-knockout mice displayed the same prevention of heart injury as insulin-treated diabetic mice. The present study demonstrated that activated nuclear beta-catenin/c-Myc axis was responsible for oxidative cardiac impairment of DCM. Therefore, repressing functional nuclear beta-catenin may provide a hopeful therapeutic strategy for DCM. PMID- 28989027 TI - Hyperglycemic condition during puberty increases collagen fibers deposition in the prostatic stroma and reduces MMP-2 activity. AB - Puberty is an important period for the growth and maturation of the male reproductive system, and is also a critical window for endocrine or environmental interference. The physiological levels of circulating insulin and hyperglycemic control are important factors for a normal prostate growth. Hyperglycemia during puberty is reported to retard the growth of the prostate gland, with remarkable effects on the epithelial compartment. Here, we investigated the impact of hyperglycemia along with a simultaneous or late insulin replacement on the ventral prostate growth in rats during puberty, paying special attention to the deposition of collagen fibers and activities of gelatinase, matrix metalloproteinase-2 (MMP-2), and -9 (MMP-9). Hyperglycemia was induced by streptozotocin (STZ) administration in 40-day-old male Wistar rats. A subset of hyperglycemic rats underwent an early insulin replacement (three days after the STZ administration), and another subset underwent a late insulin replacement (twenty days after the STZ administration). Animals were euthanized at 60 and/or 80 days of age. The ventral prostatic lobe was processed for picrosirius red staining, type I and III collagen immunohistochemistry, and gelatin zymography. Hyperglycemic animals showed an increased area of collagen fibers in the prostate, which was composed both types of collagens. MMP-2 activity was significantly reduced in the hyperglycemic animals, while MMP-9 activity was very low and showed no alteration. The simultaneous and late insulin administration restored collagen content and MMP-2 activity. In conclusion, puberty is a critical window for prostate maturation and type-1 diabetes-induced hyperglycemia affects the ratio of the prostatic parenchymal and stromal growth, leading to fibrotic tissues by also MMP-2 down regulation. PMID- 28989028 TI - Flexible nano- and microliter injections on a single liquid chromatography-mass spectrometry system: Minimizing sample preparation and maximizing linear dynamic range. AB - Lack of knowledge on the expected concentration range or insufficient linear dynamic range of the analytical method applied are common challenges for the analytical scientist. Samples that are above the upper limit of quantification are typically diluted and reanalyzed. The analysis of undiluted highly concentrated samples can cause contamination of the system, while the dilution step is time consuming and as the case for any sample preparation step, also potentially leads to precipitation, adsorption or degradation of the analytes. PMID- 28989029 TI - Applications of high-resolution recycling liquid chromatography: From small to large molecules. AB - A twin-column recycling separation process (TCRSP) is assembled and used to generate higher speed and/or higher resolution levels than those of the usual non recycling process at the same back pressure. It enables the users to solve very challenging separation problems caused by too small selectivity factors and/or too low column efficiencies. The relative gain in speed-resolution performance increases with increasing the number of cycles in the TCRSP, decreasing the maximum allowable pressure imposed by the LC system, decreasing the column permeability, and with reducing the separation speed. TCRSP is then particularly attractive for conventional LC systems (5000psi maximum) and columns packed with sub-2MUm to 3.5MUm particles. The performance of the real TCRSP was compared to that of the ideal TCRSP for which the retention factor is strictly pressure independent. A broad range of separation problems encountered in conventional non recycling chromatography can be easily solved by using a TCRSP assembly based on two 15cm long columns. Under adsorption conditions, the TCRSP enables the full baseline separation of polycyclic aromatic hydrocarbon (PAH) isomers (benzo[a]anthracene and chrysene) on a 3.5MUm XSelect-HSS T3 phase, the complete or improved resolution of racemic mixtures (4-phenylbutanol and bromacil) using the same 2.5MUm cellulose-1 chiral stationary phase, and the full resolution of isotopic compounds (benzene/1,3,5-benzene-d3/benzene-d6) on a 2.7MUm Cortecs-C18 phase. Under non-adsorption conditions or in size-exclusion chromatography (SEC), the fractionation of a polystyrene standard mixture (molecular weights of 35, 66, 130, 277, 552, 1210, and 2500kDa) was completed after only 8 cycles on a 1.7MUm BEH 200Aphase. Similarly, a mixture of intact proteins with molecular weights of 16.7, 66.4, 150, 660, and 1320kDa was fully resolved on a 2.5MUm BEH 450Aphase after only 6 cycles. Finally, TCRSP enables the complete separation of a few high molecular-weight species (monoclonal antibody aggregates, small relative abundance of 1 for 250) from the intact monomeric monoclonal antibody (Vectibix). PMID- 28989030 TI - Layer chromatography-bioassays directed screening and identification of antibacterial compounds from Scotch thistle. AB - The antibacterial profiling of Onopordum acanthium L. leaf extract and subsequent targeted identification of active compounds is demonstrated. Thin-layer chromatography (TLC) and off-line overpressured layer chromatography (OPLC) coupled with direct bioautography were utilized for investigation of the extract against eight bacterial strains including two plant and three human pathogens and a soil, a marine and a probiotic human gut bacteria. Antibacterial fractions obtaining infusion-transfusion OPLC were transferred to HPLC-MS/MS analysis that resulted in the characterization of three active compounds and two of them were identified as, linoleic and linolenic acid. OPLC method was adopted to preparative-scale flash chromatography for the isolation of the third active compound, which was identified after a further semi-preparative HPLC purification as the germacranolide sesquiterpene lactone onopordopicrin. Pure onopordopicrin exhibited antibacterial activity that was specified as minimal inhibitory concentration in the liquid phase as well. PMID- 28989031 TI - The development of a monolith-based purification process for Orthopoxvirus vaccinia virus Lister strain. AB - The purification of large viruses remains an important field of research and development. The development of efficient purification trains is restricted by limited analytical methods, as well as by the complexity of large viruses, as well as the high variability in starting material from cell culture. Vaccinia virus holds great potential as an oncolytic and immunotherapeutic vaccine against a broad spectrum of cancers. In this work, monolith-based capture and polishing chromatographic steps for vaccinia virus Lister strain has been developed. Virus produced in CV-1 cells was harvested and passed through a 0.8MUm pre-filter before loading onto CIEX, AIEX and HIC CIM monoliths. Without the need for nuclease treatment, up to 99% of the total DNA loaded can be removed from the vaccinia feed stream by the CIM OH monolith, which also reduces the total protein concentration in the product pool to LLOQ levels, and achieves infectious virus recoveries of 90%. Binding capacities of greater than 1*109pfu of vaccinia per mL of matrix were obtained on both CIM SO3 and CIM OH monoliths. Multiple orthogonal analytical methods have been used to develop process knowledge and understanding. PMID- 28989032 TI - System map for the ionic liquid stationary phase tri(tripropylphosphoniumhexanamido)triethylamine bis(trifluoromethylsulfonyl)imide for gas chromatography. AB - The solvation parameter model is used to construct a system map for the retention of volatile organic compounds on the ionic liquid stationary phase tri(tripropypphosphoniumhexanamido)triethylamine bis(trifluoromethylsulfonyl)imide (SLB-IL76) over the temperature range 80-240 degrees C. The SLB-IL76 stationary phase is moderately cohesive and strongly dipolar/polarizable and hydrogen-bond basic but only a weak hydrogen-bond acid. Electron lone pair interactions are weak and make only a minor contribution to the retention mechanism. The separation properties of SLB-IL76 highlight the difficulty of designing new stationary phases from ion structures as the presence of amide groups in the cation don't seem to contribute significantly to the hydrogen-bond acidity of SLB-IL76. The separation properties of SLB-IL76 are closest to the bis(polycyanopropyl)siloxane stationary phases with a high percentage of bis(cyanopropyl)siloxane monomer and could be used in method development when a stationary phase with similar gross retention characteristics but different selectivity is required. PMID- 28989034 TI - Tandem derivatization combined with salting-out assisted liquid-liquid microextraction for determination of biothiols in urine by gas chromatography mass spectrometry. AB - Detection of polar organic compounds (POCs) using gas chromatography (GC) is not straightforward due to high polarity, hydrophilicity, and low volatility of POCs. In this study, we report a tandem microwave-assisted derivatization method combined with salting-out assisted liquid-liquid microextraction (SALLME) to modify successively the polar groups of POCs in protic and aprotic solvents. Biothiols (cysteine and homocysteine) served as a proof of concept for this method because they possess three polar groups (thiol, amine, and carboxyl); the derivatizing reagent was 3,4,5-trifluorobenzyl bromide (Br-TFB) for alkylation. The solubility of the POCs in the protic or aprotic reaction medium affected the number of TFB molecules attached. Using the tandem derivatization with Br-TFB, the thiol and amine groups of biothiols were alkylated in the protic system, and the carboxylic groups of biothiols were alkylated in the aprotic system. The developed method was then successfully applied to measure biothiols in human urine. Because of the complex urine matrix and the lack of urine samples without endogenous biothiols, the standard addition method was utilized to avoid the matrix effect, check the recovery, and calculate the initial biothiol content in the urine. Regarding the linearity of the standard addition curves, the coefficient of determination was >0.996, and the linear regression showed satisfactory reproducibility with a relative standard deviation <3.9% for the slope and <8.8% for the intercept. The levels of cysteine and homocysteine in healthy human urine ranged from 28.8 to 111MUmolL-1 and from 1.28 to 3.73MUmolL 1, respectively. The proposed method effectively increased the sensitivity of GC MS assays of water-soluble compounds in human urine. PMID- 28989033 TI - Capillary electrophoresis-mass spectrometry for direct structural identification of serum N-glycans. AB - Through direct coupling of capillary electrophoresis (CE) to mass spectrometry (MS) with a sheathless interface, we have identified 77 potential N-glycan structures derived from human serum. We confirmed the presence of N-glycans previously identified by indirect methods, e.g., electrophoretic mobility standards, obtained 31 new N-glycan structures not identified in our prior work, differentiated co-migrating structures, and determined specific linkages on isomers featuring sialic acids. Serum N-glycans were cleaved from proteins, neutralized via methylamidation, and labeled with the fluorescent tag 8 aminopyrene-1,3,6-trisulfonic acid, which renders the glycan fluorescent and provides a -3 charge for electrophoresis and negative-mode MS detection. The neutralization reaction also stabilizes the labile sialic acids. In addition to methylamidation, native charges from sialic acids were neutralized through reaction with 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium to amidate alpha2,6-linked sialic acids in the presence of ammonium chloride and form lactones with alpha2,3-linked sialic acids. This neutralization effectively labels each type of sialic acid with a unique mass to determine specific linkages on sialylated N-glycans. For both neutralization schemes, we compared the results from microchip electrophoresis and CE. PMID- 28989035 TI - pLoc-mGneg: Predict subcellular localization of Gram-negative bacterial proteins by deep gene ontology learning via general PseAAC. AB - Information of the proteins' subcellular localization is crucially important for revealing their biological functions in a cell, the basic unit of life. With the avalanche of protein sequences generated in the postgenomic age, it is highly desired to develop computational tools for timely identifying their subcellular locations based on the sequence information alone. The current study is focused on the Gram-negative bacterial proteins. Although considerable efforts have been made in protein subcellular prediction, the problem is far from being solved yet. This is because mounting evidences have indicated that many Gram-negative bacterial proteins exist in two or more location sites. Unfortunately, most existing methods can be used to deal with single-location proteins only. Actually, proteins with multi-locations may have some special biological functions important for both basic research and drug design. In this study, by using the multi-label theory, we developed a new predictor called "pLoc-mGneg" for predicting the subcellular localization of Gram-negative bacterial proteins with both single and multiple locations. Rigorous cross-validation on a high quality benchmark dataset indicated that the proposed predictor is remarkably superior to "iLoc-Gneg", the state-of-the-art predictor for the same purpose. For the convenience of most experimental scientists, a user-friendly web-server for the novel predictor has been established at http://www.jci-bioinfo.cn/pLoc mGneg/, by which users can easily get their desired results without the need to go through the complicated mathematics involved. PMID- 28989036 TI - Reflected Vision in Surgical Practice-A Novel Method to Circumvent Posture Related Musculoskeletal Disorders. AB - Abnormal neck posture while working is a crucial factor that predisposes to incidence of musculoskeletal disorders amongst oral and maxillofacial surgeons. The related spectrum of clinical symptoms may range from severe pain in the lower and upper back, neck and TMJ to neurological deficits of the hand and wrist. These posture-related problems may be prevented by use of reflected vision that ensures a balanced neck posture during surgical procedures. PMID- 28989037 TI - Lung Cancer Patients with Germline Mutations Detected by Next-Generation Sequencing and/or Liquid Biopsy. PMID- 28989039 TI - First-Line Osimertinib in Patients with Treatment-Naive Somatic or Germline EGFR T790M-Mutant Metastatic NSCLC. PMID- 28989038 TI - Risk of Second Lung Cancer in Patients with Previously Treated Lung Cancer: Analysis of Surveillance, Epidemiology, and End Results (SEER) Data. AB - INTRODUCTION: The risk for development of a second primary lung cancer (SPLC) after treatment of an initial primary lung cancer (IPLC) is around 1% to 2% per patient per year. The present screening and surveillance guidelines do not adequately address this particular patient population. METHODS: We retrospectively reviewed patients in the Surveillance, Epidemiology, and End Results database from 1992 to 2007 to assess the frequency of occurrence of SPLC with regard to multiple patient demographics and calculated standardized incidence ratios (SIRs). RESULTS: The SIRs for SPLCs were high for both men and women at any age but highest if the IPLC occurred at a younger age. Women had the highest SIR values irrespective of age and race, with the highest SIR reported for the youngest age group (20-49 years) (SIR = 15.26, 95% confidence interval: 12.81-18.04). The rate of SPLC development was 1.10% per patient per year, with median time intervals between the IPLC and SPLC diagnoses of 59 and 62 months, respectively, for men and women. The cumulative risk for development of SPLC increased over time and did not plateau. CONCLUSIONS: These findings suggest that there is a continued risk for development of SPLC. Surveillance strategies for this population must be addressed. PMID- 28989040 TI - Molecular Adequacy of Image-Guided Rebiopsies for Molecular Retesting in Advanced Non-Small Cell Lung Cancer: A Single-Center Experience. AB - INTRODUCTION: In the era of biomarker-driven systemic therapy for advanced NSCLC, the role of routine repeated biopsies for decision making outside EGFR-mutant disease remains unproven. We report our center's experience of safety and adequacy for molecular retesting of tumor material obtained from image-guided lung rebiopsies in NSCLC. METHODS: We performed a retrospective case note analysis of patients undergoing image-guided lung rebiopsies at a single cancer center between 2011 and 2014. The primary objective was to determine the pathological success rate. Secondary and exploratory objectives were to determine technical success rate, histological concordance, molecular adequacy, genotypes identified, and complication rate. RESULTS: In all, 103 patients underwent transthoracic image-guided procedures. A total of 66 rebiopsies in NSCLC were identified and analyzed. The pathological success rate was 87.1%. A high histological discordance rate was observed (12 of 52 evaluable cases [23.1%]). Pretest molecular adequacy as determined by the lung pathologist was 78.8% (52 of 66). Of 52 adequate samples 51 were sent for molecular analysis, with a total of 209 genes analyzed (including EGFR, ALK receptor tyrosine kinase gene [ALK], KRAS, BRAF, dicoidin domain receptor tyrosine kinase 2 gene [DDR2], NRAS, ROS1, and rearranged during transfection proto-oncogene gene [RET]). The rate of postgenotyping molecular adequacy was 87.1% (182 of 209). Overall, 20 new potentially actionable mutations were identified, with 13 of 66 patients (19.7%) starting to receive new targeted treatment as a result. Overall, rebiopsies informed clinical decision making in 63.6% of cases. The rates of complications were 15% for pneumothorax, 3% for pneumothorax requiring chest drain, and 8% for hemoptysis. CONCLUSIONS: We have validated the pathological and molecular adequacy rates of rebiopsies and demonstrated clinical utility in routine decision making. PMID- 28989041 TI - Deciphering molecular mechanisms of arginine deiminase-based therapy - Comparative response analysis in paired human primary and recurrent glioblastomas. AB - Arginine auxotrophy constitutes the Achilles' heel for several tumors, among them glioblastoma multiforme (GBM). Hence, arginine-depleting enzymes such as arginine deiminase (ADI) from Streptococcus pyogenes are promising for treatment of primary and maybe even refractory GBM. Based on our previous study in which ADI susceptibility was shown on a panel of patient-derived GBM cell lines, we here aimed at deciphering underlying molecular mechanisms of ADI-mediated growth inhibition. We found that ADI (35 mU/mL) initially induces a cellular stress response that is characterized by upregulation of genes primarily belonging to the heat-shock protein family. In addition to autophagocytosis, we show for the first time that senescence constitutes another cellular response mechanism upon ADI-treatment and that this bacterial enzyme is able to act as radiosensitizer (1/4 cases). Long-term treatment schedules revealed no resistance development, with treated cells showing morphological signs of cell stress. Next, several combination strategies were employed to optimize ADI-based treatment. Simultaneous and sequential S. pyogenes ADI-based combinations included substances acting at different molecular pathways (curcumin, resveratrol, quinacrine, and sorafenib, 2 * 72 h treatment). Adding drugs to GBM cell lines (n = 4, including a matched pair of primary and recurrent GBM in one case) accelerated and potentiated ADI-mediated cytotoxicity. Autophagy was identified as the main cause of tumor growth inhibition. Of note, residual cells again showed classical signs of senescence in most combinations. Our results suggest an alternative treatment regimen for this fatal cancer type which circumvents many of the traditional barriers. Using the metabolic defect in GBM thus warrants further (pre-) clinical evaluation. PMID- 28989042 TI - Identification of Driver Genes and Key Pathways of Glioblastoma Shows JNJ-7706621 as a Novel Antiglioblastoma Drug. AB - OBJECTIVE: The aim of this study is to identify novel targets of diagnosis, therapy, and prognosis for glioblastoma, as well as to verify the therapeutic effect of JNJ-7706621 regarding glioblastoma. METHODS: The gene expression profiles of GSE42656, GSE50161, and GSE86574 were obtained respectively from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) were identified with comparison between gene expression profiles of the glioblastoma tissues and normal tissues. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and protein-protein interaction (PPI) network analyses were performed. Quantitative reverse transcription polymerase chain reaction and survival curve analysis were also conducted to verify the correlation between expression of hub genes and prognosis. Moreover, in vitro, MTT assay, colony forming assay, the scratch assay, and flow cytometry were performed to verify the therapeutic effect of JNJ-7706621. RESULTS: AURKA, NDC80, KIF4A, and NUSAP1 were identified as hub genes after PPI network analysis. Differential expression of those genes was detected between human normal glial cells and glioblastoma cells by quantitative reverse transcription polymerase chain reaction (P < 0.05), and the survival curve analysis showed that the patients with low expression of gene AURKA, NDC80, KIF4A, and NUSAP1 had a significant favorable prognosis (P < 0.05). In vitro assays showed that JNJ-7706621 inhibited glioblastoma cellular viability, proliferation, and migration via inducing glioblastoma cells apoptosis. CONCLUSIONS: AURKA, NDC80, KIF4A, and NUSAP1 were significantly more highly expressed in glioblastoma cells than in human normal glial cell. Patients with low expression of those 4 genes had a favorable prognosis. JNJ-7706621 was a potential drug in treatment of patients with glioblastoma. PMID- 28989043 TI - Cerebrospinal Fluid Leak at Percutaneous Exit of Ventricular Catheter as a Crucial Risk Factor for External Ventricular Drainage-Related Infection in Adult Neurosurgical Patients. AB - OBJECTIVE: The placement of a ventricular catheter for temporary cerebrospinal fluid (CSF) diversion is associated with a considerable risk of CSF infection. The authors investigated the effect of a CSF leak on CSF-related infection and the predisposing factors for a CSF leak. METHODS: Fifty-two patients who underwent external ventricular drainage (EVD) for acute hydrocephalus associated with a subarachnoid hemorrhage or intraventricular hemorrhage (IVH) were enrolled in this prospective study. A CSF leak-detection paper (small sterilized filter paper) was applied at the percutaneous catheter exit site to check for any bloody CSF leak. In addition, radiologic and clinical data were collected. RESULTS: Four of the 52 patients (7.7%) developed an EVD-related CSF infection from organisms including Staphylococcus epidermidis (n = 3) and Staphylococcus hominis (n = 1). A prolonged CSF leak >1 day was detected in 9 patients (17.3%) and revealed as a significant risk factor for CSF infection with a 44.4% positive predictive value. Moreover, an IVH >10 mL was found in 11 patients (21.2%) and revealed as a significant predisposing factor for a CSF leak at the percutaneous catheter exit. CONCLUSIONS: A prolonged CSF leak for >1 day at the percutaneous catheter exit site is a crucial risk factor for EVD-related CSF infection and an IVH >10 mL is a predisposing factor for a CSF leak. PMID- 28989044 TI - Preoperative Navigated Transcranial Magnetic Stimulation and Tractography to Guide Endoscopic Cystoventriculostomy: A Technical Note and Case Report. AB - OBJECTIVE: To report a technique for endoscopic cystoventriculostomy guided by preoperative navigated transcranial magnetic stimulation (nTMS) and tractography in a patient with a large speech eloquent arachnoid cyst. METHODS: A 74-year old woman presented with a seizure and subsequent persistent anomic aphasia from a progressive left-sided parietal arachnoid cyst. An endoscopic cystoventriculostomy and endoscope-assisted ventricle catheter placement were performed. Surgery was guided by preoperative nTMS and tractography to avoid eloquent language, motor, and visual pathways. RESULTS: Preoperative nTMS motor and language mapping were used to guide tractography of motor and language white matter tracts. The ideal locations of entry point and cystoventriculostomy as well as trajectory for stent-placement were determined preoperatively with a pseudo-3-dimensional model visualizing eloquent language, motor, and visual cortical and subcortical information. The early postoperative course was uneventful. At her 3-month follow-up visit, her language impairments had completely recovered. Additionally, magnetic resonance imaging demonstrated complete collapse of the arachnoid cyst. CONCLUSION: The combination of nTMS and tractography supports the identification of a safe trajectory for cystoventriculostomy in eloquent arachnoid cysts. PMID- 28989045 TI - Reappraisal of Neonatal Greenstick Skull Fractures Caused by Birth Injuries: Comparison of 3-Dimensional Reconstructed Computed Tomography and Simple Skull Radiographs. AB - OBJECTIVE: The most common birth-associated head injuries during vaginal delivery are cephalhematomas and subgaleal hematomas. Cranial injuries are rarely encountered. The neonate cranium is soft and pliable, and greenstick skull fractures (GSFs) are expected to be more frequent than linear or depressed fractures, but they are extremely difficult to detect with simple skull radiography. As a result, no reports have been issued on this topic to date. Recent reports suggest that technological advances in 3-dimensional (3D) computed tomography (CT) have successfully enhanced the diagnostic accuracy for cranial fractures. The authors researched the types and characteristics of GSFs and the diagnostic accuracy of 3D CT for cranial fractures in neonates. METHODS: The simple skull radiographs and 3D CT images of 101 neonates were retrospectively evaluated and compared with respect to diagnosis of cranial fractures, and skull GSFs were classified on the basis of 3D CT findings into 5 types depending on multiplicity and location. RESULTS: 3D CT detected 88 cases of cranial fractures, that is, 89 GSFs, 4 combined GSFs and linear fractures, and 3 combined GSFs and depressed fractures. The diagnostic rate of 3DCT was 91% and this was significantly higher than the 13% rate of simple skull radiographs (P < 0.001). CONCLUSIONS: GSFs rather than linear fractures were found to account for most cranial injuries among neonates. The diagnostic accuracy of 3D CT was considerably superior than simple skull radiography, but the high radiation exposure levels of 3D CT warrant the need for development of a modality with lower radiation exposure. PMID- 28989046 TI - Modular Classification of Endoscopic Endonasal Transsphenoidal Approaches to Sellar Region: Anatomic Quantitative Study. AB - BACKGROUND: Endoscopic visualization does not necessarily correspond to an adequate working space. The need for balancing invasiveness and adequacy of sellar tumor exposure has recently led to the description of multiple endoscopic endonasal transsphenoidal approaches. Comparative anatomic data on these variants are lacking. OBJECT: We sought to quantitatively compare endoscopic endonasal transsphenoidal approaches to the sella and parasellar region, using the concept of "surgical pyramid." METHODS: Four endoscopic transsphenoidal approaches were performed in 10 injected specimens: 1) hemisphenoidotomy; 2) transrostral; 3) extended transrostral (with superior turbinectomy); and 4) extended transrostral with posterior ethmoidectomy. ApproachViewer software (part of GTx-Eyes II, University Health Network, Toronto, Canada) with a dedicated navigation system was used to quantify the surgical pyramid volume, as well as exposure of sellar and parasellar areas. Statistical analyses were performed with Friedman's tests and Nemenyi's procedure. RESULTS: Hemisphenoidotomy provided limited exposure of the sellar area and a small working volume. A transrostral approach was necessary to expose the entire sella. Exposure of lateral parasellar areas required superior turbinectomy or posterior ethmoidectomy. The differences between each of the modules was statistically significant. CONCLUSION: The present study validates, from an anatomic point of view, a modular classification of endoscopic endonasal transsphenoidal approaches to the sellar region. PMID- 28989047 TI - Delayed Complications After Transsphenoidal Surgery for Pituitary Adenomas. AB - Perioperative complications after transsphenoidal surgery for pituitary adenomas have been well documented in the literature; however, some complications can occur in a delayed fashion postoperatively, and reports are sparse about their occurrence, management, and outcome. Here, we describe delayed complications after transsphenoidal surgery and discuss the incidence, temporality from the surgery, and management of these complications based on the findings of studies that reported delayed postoperative epistaxis, delayed postoperative cavernous carotid pseudoaneurysm formation and rupture, vasospasm, delayed symptomatic hyponatremia, hypopituitarism, hydrocephalus, and sinonasal complications. Our findings from this review revealed an incidence of 0.6%-3.3% for delayed postoperative epistaxis at 1-3 weeks postoperatively, 18 reported cases of delayed carotid artery pseudoaneurysm formation at 2 days to 10 years postoperatively, 30 reported cases of postoperative vasospasm occurring 8 days postoperatively, a 3.6%-19.8% rate of delayed symptomatic hyponatremia at 4-7 days postoperatively, a 3.1% rate of new-onset hypopituitarism at 2 months postoperatively, and a 0.4%-5.8% rate of hydrocephalus within 2.2 months postoperatively. Sinonasal complications are commonly reported after transsphenoidal surgery, but spontaneous resolutions within 3-12 months have been reported. Although the incidence of some of these complications is low, providing preoperative counseling to patients with pituitary tumors regarding these delayed complications and proper postoperative follow-up planning is an important part of treatment planning. PMID- 28989048 TI - Supraorbital Keyhole Approach to the Sella and Anterior Skull Base via a Forehead Wrinkle Incision. AB - OBJECTIVE: To evaluate safety and effectiveness of supraorbital keyhole approach to the sella and anterior skull base via a forehead wrinkle incision. METHODS: We analyzed and reclassified forehead wrinkle types in 100 recruited healthy individuals. Twenty patients with different intracranial lesions in the sella and anterior skull base areas were selected for surgery using the supraorbital keyhole approach via a forehead wrinkle incision by forehead wrinkle type. All clinical patient records were retrospectively reviewed. RESULTS: Based on the feasibility of the surgical approach, the forehead wrinkles in Chinese individuals were categorized into 2 types: horizontal linear and nonlinear. Gross total removal of the lesions was achieved in 90% of the cases using this approach. All patients had excellent cosmetic results. Except for 2 patients with poor prognoses, a high level of comfort and satisfaction with the forehead wrinkle incisions was obtained based on the scale scores of pain from scars and headaches and satisfaction with the cosmetic results. No permanent approach related complications occurred. CONCLUSIONS: The supraorbital keyhole approach via a forehead wrinkle incision was safe and effective. This approach provided a sufficient visual field for lesion resection and satisfactory cosmetic results for patients. PMID- 28989049 TI - Individual Variability of the Human Cerebral Cortex Identified Using Intraoperative Mapping. AB - BACKGROUND: Intraoperative functional cortical mapping using direct electrical stimulation may show a wider individual variability than suggested by noninvasive imaging data of healthy subjects. METHODS: We assessed intraoperative variability of the frontal eye fields and the speech arrest sites in adult patients who underwent awake craniotomy with direct electrostimulation for treatment of diffuse gliomas located within eloquent regions, and we compared findings with human cortical parcellation of the Human Connectome Project. RESULTS: The frontal eye fields were defined by intraoperative direct electrostimulations (14.3% of patients) projected on the superior subdivision of the premotor cortex covering the areas defined as frontal eye fields (parcel index 10), area 55b (parcel index 12), and premotor eye field (parcel index 11) and in the posterior part of the dorsolateral prefrontal cortex covering the areas defined as inferior 6-8 transitional area (parcel index 97), area 8Av (parcel index 67), and area 8C (parcel index 73). The speech arrest sites were defined by intraoperative direct electrostimulations (100% of patients) projected predominantly posteriorly to the inferior frontal gyrus in the inferior subdivision of the premotor cortex, that is, rostral area 6 (parcel index 78), ventral area 6 (parcel index 54), and area 43 (parcel index 99). CONCLUSIONS: Intraoperative functional cortical mapping using direct electrostimulation highlights that actual individual variability is wider than suggested by analyses of healthy subjects and results in atypical patterns of functional organization and structural and functional changes of the human cerebral cortex under pathologic conditions. PMID- 28989051 TI - The effect of taxation and regulation on cigarette smoking: Fresh evidence from Turkey. AB - Enacting Law No 5247 in May 2008, Turkey has initiated crucial anti-tobacco policies in the last decade. This paper aims to reveal on the effect of anti tobacco policies such as excise taxes and regulations on cigarette smoking. To this aim, I empirically investigate the long-term dynamics of demand for cigarettes in Turkey through the OLS estimation strategy under various scenarios and models. Using monthly and quarterly data that cover the pre- and post- anti smoking policy periods, I estimate demand elasticities and compare the pre- and post- taxation and regulation terms. The results presented in the paper confirm that taxation and regulation have affected the long-term dynamics of demand for cigarettes. The price and income elasticities of demand for cigarettes are significantly higher than the previous literature on Turkey. Demand elasticities have increased on average in the anti-tobacco policies period. PMID- 28989050 TI - Novel Application of Time-Spatial Labeling Inversion Pulse Magnetic Resonance Imaging for Diagnosis of External Hydrocephalus. AB - BACKGROUND: Although a subdural fluid collection frequently is observed, diagnostic methods that differentiate between the subdural collection caused by external hydrocephalus and that caused by subdural hygroma have not been established. Here, we report a case of external hydrocephalus caused by Gliadel induced eosinophilic meningitis that has been previously reported in only 1 case and can be diagnosed by time-spatial labeling inversion pulse magnetic resonance imaging (time-SLIP MRI). CASE DESCRIPTION: A tumor located in the left temporal was detected incidentally in an 81-year-old man by examination of a head injury. The tumor was surgically resected and diagnosed as a high-grade glioma during the surgery; Gliadel wafers subsequently were implanted. Three weeks after the resection, the patient showed disturbed consciousness, and computed tomography revealed a subdural fluid collection. The out-flow of cerebrospinal through the resection cavity was detected by time-SLIP MRI. Cerebrospinal tests indicated high white blood cell counts and high protein levels, with more than 90% of the white blood cell count comprising eosinophils. Therefore, we suspected that the subdural fluid collection was caused by external hydrocephalus because of Gliadel induced eosinophilic meningitis. We surgically removed the Gliadel wafers and subsequently performed a surgery to insert a ventriculoperitoneal shunt. Histologic examination indicated eosinophilic accumulation around the Gliadel wafers. The patient's symptoms improved after the insertion of a ventriculoperitoneal shunt. CONCLUSIONS: In the present case, time-SLIP MRI was a useful and noninvasive method for diagnosing external hydrocephalus which was caused by eosinophilic meningitis because of Gliadel-induced eosinophilic meningitis. PMID- 28989053 TI - PDGFs and their receptors in vascular stem/progenitor cells: Functions and therapeutic potential in retinal vasculopathy. AB - Vascular stem/progenitor cells (VSCs) include endothelial progenitor cells, smooth muscle progenitor cells, pericytes, and mesenchymal stem cells. VSCs can produce functional and mature vascular cells required to build blood vessels. VSCs therefore play critical roles in vascular repair and regeneration, particularly, in various retinal vasculopathies, in which vascular defects are a devastating pathology. The platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) are important regulators of numerous physiological events and diseases, and they play key roles in regulating the formation and function of blood vessels. A better understanding of the effects of PDGFs/PDGFRs on VSCs and a thorough elucidation of their therapeutic potential in the treatment of retinal vasculopathies are critical for both basic and translational research and may lead to better therapies for human vascular diseases. PMID- 28989052 TI - In silico analysis of cytochrome P450 monooxygenases in chronic granulomatous infectious fungus Sporothrix schenckii: Special focus on CYP51. AB - Sporotrichosis is an emerging chronic, granulomatous, subcutaneous, mycotic infection caused by Sporothrix species. Sporotrichosis is treated with the azole drug itraconazole as ketoconazole is ineffective. It is a well-known fact that azole drugs act by inhibiting cytochrome P450 monooxygenases (P450s), heme thiolate proteins. To date, nothing is known about P450s in Sporothrix schenckii and the molecular basis of its resistance to ketoconazole. Here we present genome wide identification, annotation, phylogenetic analysis and comprehensive P450 family-level comparative analysis of S. schenckii P450s with pathogenic fungi P450s, along with a rationale for ketoconazole resistance by S. schenckii based on in silico structural analysis of CYP51. Genome data-mining of S. schenckii revealed 40 P450s in its genome that can be grouped into 32 P450 families and 39 P450 subfamilies. Comprehensive comparative analysis of P450s revealed that S. schenckii shares 11 P450 families with plant pathogenic fungi and has three unique P450 families: CYP5077, CYP5386 and CYP5696 (novel family). Among P450s, CYP51, the main target of azole drugs was also found in S. schenckii. 3D modeling of S. schenckii CYP51 revealed the presence of characteristic P450 motifs with exceptionally large reductase interaction site 2. In silico analysis revealed number of mutations that can be associated with ketoconazole resistance, especially at the channel entrance to the active site. One of possible reason for better stabilization of itraconazole, compared to ketoconazole, is that the more extended molecule of itraconazole may form a hydrogen bond with ASN-230. This in turn may explain its effectiveness against S. schenckii vis-a-vis resistant to ketoconazole. This article is part of a Special Issue entitled: Cytochrome P450 biodiversity and biotechnology, edited by Erika Plettner, Gianfranco Gilardi, Luet Wong, Vlada Urlacher, Jared Goldstone. PMID- 28989054 TI - Nuclear Met promotes hepatocellular carcinoma tumorigenesis and metastasis by upregulation of TAK1 and activation of NF-kappaB pathway. AB - Presence of Met receptor tyrosine kinase in the nucleus of cells has been reported. However, the functions of Met which expresses in the nucleus (nMet) remain elusive. In this study, we found that nMet was increased in 89% of HCC tumorous tissues when compared with the corresponding non-tumorous liver tissues. nMet expression increased progressively along HCC development and significantly correlated with cirrhosis, poorer cellular differentiation, venous invasion, late stage HCC and poorer overall survival. Western blot analysis revealed that nMet is a 48-kDa protein comprising the carboxyl terminal of Met receptor. Induced expression of nMet promoted HCC cell growth, migration and invasiveness in vitro and tumorigenesis and pulmonary metastasis in vivo. Luciferase assay showed that nMet activated NF-kappaB pathway. Indeed, p-IKKalpha/beta and nuclear p-p65 were higher in nMet stable cells than in the control cells. Perturbation of TAK1/NF kappaB axis abrogated the aggressiveness of HCC cells, both in vitro and in vivo. In conclusion, nMet was overexpressed and as a potential prognostic biomarker of HCC. Functionally, nMet accelerated HCC tumorigenesis and metastasis via the activation of TAK1/NF-kappaB pathway. PMID- 28989055 TI - Down-regulation of HECTD3 by HER2 inhibition makes serous ovarian cancer cells sensitive to platinum treatment. AB - Resistance to platinum-based chemotherapy is a major cause of treatment failure in patients with epithelial ovarian cancer and predicts a poor prognosis. Previously, we found that HECTD3 confers cancer cell resistance to apoptosis. However, the significance of HECTD3 expression in ovarian cancer and its regulatory mechanisms were unknown. Here, we found that HECTD3 depletion promotes carboplatin-induced apoptosis in both an ovarian cancer cell model and a xenograft mouse model. Moreover, high HECTD3 expression is significantly associated with poor platinum response and prognosis in ovarian cancer patients. We further demonstrated that HER2 can up-regulate HECTD3 expression through activating STAT3. Furthermore, HER2 inhibitors, such as lapatinib, down-regulate HECTD3 expression and thus promote the chemosensitivity of ovarian cancer cells to carboplatin. Lapatinib combined with carboplatin also significantly inhibits serous ovarian carcinoma growth compared with each drug alone in a xenograft mouse model. HECTD3 may be considered a promising molecular predictor of platinum chemosensitivity and prognosis for serous ovarian cancer. Through decreasing HECTD3, lapatinib possesses significantly increased anti-tumor activity when combined with carboplatin compared with each agent alone, which provides an optional therapeutic regimen for serous ovarian cancer. PMID- 28989056 TI - Engineering nanomaterials to overcome the mucosal barrier by modulating surface properties. AB - Although nanotechnology has been investigated during recent years to increase the bioavailability and therapeutic effects of mucosal administrated drugs, numerous barriers (e.g., pH environment, enzymes and mucus) still limit the delivery efficiency. And the epithelium would also affect the systemic mucosal drug delivery. Amongst all the barriers, the protective mucus has drawn more and more attention, which strongly hinders the accessibility of nanovehicles to epithelium. Therefore, trials to conquer the mucus barrier have been designed using two controversial strategies: mucoadhesion and mucus-penetration. This review summarizes the influence of mucus layer on nanomaterials and introduces the modification strategies by modulating surface properties (i.e., hydrophilicity/hydrophobicity and surface charge) to overcome mucus barriers. Furthermore, it also reviews advanced modification methods to meet the different surface requirements of nanovehicles to overcome mucus and epithelium barriers in systemic mucosal delivery. PMID- 28989057 TI - A prospective pilot study of the efficacy and safety of Elipse intragastric balloon: A single-center, single-surgeon experience. AB - BACKGROUND: ElipseTM is the least invasive IGB for weight loss that needs no sedation or endoscopy. It is a swallowable capsule filled with 550 mL of fluid, which stays in the stomach for 16 weeks and is excreted from the gastrointestinal tract. Kuwait is one of the first countries to start using ElipseTM as a weight loss device. This study aims to evaluate the efficacy and safety of ElipseTM intragastric balloon (IGB). MATERIALS AND METHODS: This is a single-center prospective pilot study of 51 ElipseTM insertions at our clinic. The patients were followed for 4 months to monitor their weight and body mass index (BMI) at 1, 2, and 4 months. Total weight loss, % excess weight loss (%EWL), % total body weight loss (%TBWL), and change in BMI and waist circumference (WC) were recorded at the end of the study. A short survey was administered to evaluate symptoms, complications, and overall satisfaction. RESULTS: Fifty-one patients participated, of which five had ElipseTM removed because of intolerance. One case vomited the balloon; one had early deflation. The total weight loss was 8.84 kg, %TBWL 10.44%, %EWL 40.84%, change in BMI 3.42 kg/m2, and the total WC reduction 8.62 cm. Symptoms after insertion were severe, whereas those during excretion were mild and self-limiting. No serious complications were recorded, and the overall satisfaction was above average. CONCLUSION: Our data proves that ElipseTM is a safe and effective device for weight loss. Nevertheless, some limitations were observed that need to be overcome for better outcomes. Larger studies are needed to support our findings. PMID- 28989058 TI - What Does Fatty Mesenteric Lymphadenopathy Mean? PMID- 28989060 TI - Metroticket 2.0 Model for Analysis of Competing Risks of Death After Liver Transplantation for Hepatocellular Carcinoma. AB - BACKGROUND & AIMS: Outcomes of liver transplantation for hepatocellular carcinoma (HCC) are determined by cancer-related and non-related events. Treatments for hepatitis C virus infection have reduced non-cancer events among patients receiving liver transplants, so reducing HCC-related death might be an actionable end point. We performed a competing-risk analysis to evaluate factors associated with survival of patients with HCC and developed a prognostic model based on features of HCC patients before liver transplantation. METHODS: We performed multivariable competing-risk regression analysis to identify factors associated with HCC-specific death of patients who underwent liver transplantation. The training set comprised 1018 patients who underwent liver transplantation for HCC from January 2000 through December 2013 at 3 tertiary centers in Italy. The validation set comprised 341 consecutive patients who underwent liver transplantation for HCC during the same period at the Liver Cancer Institute in Shanghai, China. We collected pretransplantation data on etiology of liver disease, number and size of tumors, patient level of alpha-fetoprotein (AFP), model for end-stage liver disease score, tumor stage, numbers and types of treatment, response to treatments, tumor grade, microvascular invasion, dates, and causes of death. Death was defined as HCC-specific when related to HCC recurrence after transplantation, disseminated extra- and/or intrahepatic tumor relapse and worsened liver function in presence of tumor spread. The cumulative incidence of death was segregated for hepatitis C virus status. RESULTS: In the competing-risk regression, the sum of tumor number and size and of log10 level of AFP were significantly associated with HCC-specific death (P < .001), returning an average c-statistic of 0.780 (95% confidence interval, 0.763-0.798). Five-year cumulative incidence of non-HCC-related death was 8.6% in HCV-negative patients and 18.1% in HCV-positive patients. For patients with HCC to have a 70% chance of HCC-specific survival 5 years after transplantation, their level of AFP should be <200 ng/mL and the sum of number and size of tumors (in centimeters) should not exceed 7; if the level of AFP was 200-400 ng/mL, the sum of the number and size of tumors should be <=5; if their level of AFP was 400-1000 ng/mL, the sum of the number and size of tumors should be <=4. In the validation set, the model identified patients who survived 5 years after liver transplantation with 0.721 accuracy (95% confidence interval, 0.648%-0.793%). Our model, based on patients' level of AFP and HCC number and size, outperformed the Milan; University of California, San Francisco; Shanghai-Fudan; Up-to-7 criteria (P < .001); and AFP French model (P = .044) to predict which patients will survive for 5 years after liver transplantation. CONCLUSIONS: We developed a model based on level of AFP, tumor size, and tumor number, to determine risk of death from HCC-related factors after liver transplantation. This model might be used to select end points and refine selection criteria for liver transplantation for patients with HCC. To predict 5-year survival and risk of HCC-related death using an online calculator, please see www.hcc-olt-metroticket.org/. ClinicalTrials.gov ID NCT02898415. PMID- 28989059 TI - Clinical Practice Update: The Use of Per-Oral Endoscopic Myotomy in Achalasia: Expert Review and Best Practice Advice From the AGA Institute. AB - The purpose of this review is to describe a place for per-oral endoscopic myotomy (POEM) among the currently available robust treatments for achalasia. The recommendations outlined in this review are based on expert opinion and on relevant publications from PubMed and EMbase. The Clinical Practice Updates Committee of the American Gastroenterological Association proposes the following recommendations: 1) in determining the need for achalasia therapy, patient specific parameters (Chicago Classification subtype, comorbidities, early vs late disease, primary or secondary causes) should be considered along with published efficacy data; 2) given the complexity of this procedure, POEM should be performed by experienced physicians in high-volume centers because an estimated 20-40 procedures are needed to achieve competence; 3) if the expertise is available, POEM should be considered as primary therapy for type III achalasia; 4) if the expertise is available, POEM should be considered as treatment option comparable with laparoscopic Heller myotomy for any of the achalasia syndromes; and 5) post-POEM patients should be considered high risk to develop reflux esophagitis and advised of the management considerations (potential indefinite proton pump inhibitor therapy and/or surveillance endoscopy) of this before undergoing the procedure. PMID- 28989061 TI - A Case of Unusual Ileal Discoloration. PMID- 28989062 TI - A Rare Submucosal Tumor of The Colon. PMID- 28989064 TI - A Rare Cause of Gastric Wall Thickening. PMID- 28989065 TI - Appendiceal Tumor or Something More? PMID- 28989067 TI - Phylogenies based on combined mitochondrial and nuclear sequences conflict with morphologically defined genera in the eimeriid coccidia (Apicomplexa). AB - Partial mitochondrial (mt) cytochrome c oxidase subunit I (COI) and near-complete nuclear (nu) 18S rDNA sequences were obtained from various eimeriid coccidia infecting vertebrates. New and published sequences were used in phylogenetic reconstructions based on nu 18S rDNA, mt COI and concatenated sequence datasets. Bayesian analyses of nu 18S rDNA sequences used secondary structure-based alignments with a doublet nucleotide substitution model; the codon nucleotide substitution model was applied to COI sequences. Although alignment of the mt COI sequences was unambiguous, substitution saturation was evident for comparisons of COI sequences between ingroup (eimeriid) and outgroup (sarcocystid) taxa. Consequently, a combined dataset applying partition-specific analytical and alignment improvements was used to generate a robust molecular phylogeny. Most eimeriid parasites that infect closely related definitive hosts were found in close proximity on the resulting tree, frequently in a single clade. Whether this represents coevolution or co-accommodation or a combination remains an open point. Unlike host associations, basic oocyst configuration (number of sporocysts per oocyst and sporozoites per sporocyst) was not correlated with phylogeny. Neither 'Eimeria-type' nor 'Isospora-type' oocyst morphotypes formed monophyletic groups. In the combined dataset tree (representing only a tiny fraction of described eimeriid coccidia), at least 10 clades of Eimeria spp. would need to be re-assigned to nine distinct genera to resolve their paraphyly. The apparent lack of congruence between morphotype and genotype will require taxonomists to balance nomenclatural stability and diagnostic ease against the ideal of monophyletic genera. For now, recognition of paraphyletic eimeriid genera defined by basic oocyst configuration may be necessary for reasons of taxonomic stability and diagnostic utility. Future taxonomic revisions to produce monophyletic eimeriid genera will ultimately require the identification of reliable phenotypic characters that agree with the molecular phylogeny of these parasites or, less optimally, acceptance that genotyping may be needed to support monophyletic supraspecific taxonomic groups. PMID- 28989066 TI - Interleukin 35 Expression Correlates With Microvessel Density in Pancreatic Ductal Adenocarcinoma, Recruits Monocytes, and Promotes Growth and Angiogenesis of Xenograft Tumors in Mice. AB - BACKGROUND & AIMS: Cells of the monocyte lineage contribute to tumor angiogenesis. Interleukin 35 (IL35) is a member of the IL12 family produced by regulatory, but not effector, T cells. IL35 is a dimer comprising the IL12 alpha and IL27 beta chains, encoded by IL12A and EBI3, respectively. Expression of IL35 is increased in pancreatic ductal adenocarcinomas (PDACs) compared with normal pancreatic tissues, and promotes metastasis. We investigated the role of IL35 in monocyte-induced angiogenesis of PDAC in mice. METHODS: We measured levels of IL35 protein, microvessel density, and numbers of monocytes in 123 sequential PDAC tissues from patients who underwent surgery in China in 2010. We performed studies with the human PDAC cell lines CFPAC-1, BxPC-3, Panc-1, MIA-PaCa-2, and mouse PDAC cell line Pan02. Monocyte subsets were isolated by flow cytometry from human peripheral blood mononuclear cells. Fused human or mouse IL12A and EBI3 genes were overexpressed in PDAC cells or knocked down using small hairpin RNAs. Cells were grown as xenograft tumors in SCID mice; some mice were given injections of an IL35-neutralizing antibody and tumor growth was monitored. We performed chemotaxis assays to measure the ability of IL35 to recruit monocytes. We analyzed mRNA sequences of 179 PDACs in the Cancer Genome Atlas to identify correlations between expression of IL12A and EBI3 and monocyte markers. Monocytes incubated with IL35 or PDAC cell supernatants were analyzed in tube formation and endothelial migration assays. RESULTS: In PDAC samples from patients, levels of IL35 mRNA and protein correlated with microvessel density and infiltration of monocyte lineage cells. In cells and mice with xenograft tumors, IL35 increased recruitment of monocytes into PDAC tumors, which required CCL5. Upon exposure to IL35, monocytes increased expression of genes whose products promote angiogenesis (CXCL1 and CXCL8). IL35 activated transcription of CCL5, CXCL1, and CXCL8 by inducing GP130 signaling, via IL12RB2 and phosphorylation of STAT1 and STAT4. A combination of a neutralizing antibody against IL35 and gemcitabine significantly decreased monocyte infiltration, microvessel density, and volume of xenograft tumors grown from PDAC cells in mice. CONCLUSIONS: PDAC cells produce IL35 to recruit monocytes via CCL5 and induce macrophage to promote angiogenesis via expression of CXCL1 and CXCL8. IL35 signaling promotes angiogenesis and growth of xenograft tumors from PDAC cells in mice. IL35 might serve as a therapeutic target for patients with pancreatic cancer. PMID- 28989068 TI - Transcriptome and toxin family analysis of the paralysis tick, Ixodes holocyclus. AB - The Australian paralysis tick (Ixodes holocyclus) secretes neuropathic toxins into saliva that induce host paralysis. Salivary glands and viscera were dissected from fully engorged female I. holocyclus ticks collected from dogs and cats with paralysis symptoms. cDNA from both tissue samples were sequenced using Illumina HiSeq 100 bp pair end read technologies. Unique and non-redundant holocyclotoxin sequences were designated as HT2-HT19, as none were identical to the previously described HT1. Specific binding to rat synaptosomes was determined for synthetic HTs, and their neurotoxic capacity was determined by neonatal mouse assay. They induced a powerful paralysis in neonatal mice, particularly HT4 which produced rapid and strong respiratory distress in all animals tested. This is the first known genomic database developed for the Australian paralysis tick. The database contributed to the identification and subsequent characterization of the holocyclotoxin family that will inform the development of novel anti-paralysis control methods. PMID- 28989069 TI - The role of biomarkers in dilated cardiomyopathy: Assessment of clinical severity and reverse remodeling. AB - INTRODUCTION: Biomarkers in dilated cardiomyopathy (DCM) reflect various pathobiological processes, including neurohormonal activation, oxidative stress, matrix remodeling, myocyte injury and myocyte stretch. We assessed the role of biomarkers in clinical and echocardiographic parameters and in left ventricular (LV) reverse remodeling (LVRR). METHODS: In this prospective study of 50 DCM patients (28 men, aged 59+/-10 years) with LV ejection fraction (LVEF) <40%, LVRR was defined as an increase of >10 U in LVEF after optimal medical therapy. RESULTS: Baseline LVEF was 25.4+/-9.8% and LV end-diastolic diameter (LVEDD)/body surface area (BSA) was 34.2+/-4.5 mm/m2. LVRR occurred in 34% of patients within 17.6+/-15.6 months. No correlation was found between B-type natriuretic peptide (BNP), 25-hydroxyvitamin D (25(OH)D), CA-125, high-sensitivity C-reactive protein (hs-CRP), lipoprotein(a) [Lp(a)], noradrenaline, adrenaline, renin or aldosterone and LVRR. Patients in NYHA class III or IV, with pulmonary congestion or ankle edema, had higher CA-125, cystatin C, BNP and hs-CRP levels (p<0.05). CA-125 was correlated with BNP (r=0.61), hs-CRP (r=0.56) and uric acid (r=0.52) (all p=0.01). BNP correlated directly with LVEDD (r=0.49), LV volumes (r=0.51), pulmonary artery systolic pressure (PASP) (r=0.43) and E/e' (r=0.31), and was inversely correlated with LVEF (r=-0.50) and e' velocity (r=-0.32) (p<0.05). CA 125 was positively correlated with left atrial volume/BSA (r=0.46), E/A ratio (r=0.60) and PASP (r=0.49) (p<0.05). CONCLUSIONS: No correlation was found between biomarkers and LVRR, but CA-125, BNP and hs-CRP were predictors of clinical severity and congestion. BNP correlated with parameters of systolic and diastolic dysfunction, while CA-125 correlated with measures of diastolic dysfunction. PMID- 28989070 TI - Personal-level exposure to environmental temperature is a superior predictor of endothelial-dependent vasodilatation than outdoor-ambient level. AB - Environmental temperatures influence cardiovascular physiology. However, the majority of time is spent indoors, making outdoor-ambient temperatures inaccurate estimates of true exposures encountered by most individuals. We evaluated in 50 healthy adults the associations between previous 7-day outdoor-ambient (four occasions) and prior 24-hour personal-level (two occasions) environmental temperature exposures with blood pressure, heart rate variability, sleep parameters, and endothelial-dependent vasodilatation (brachial flow-mediated dilatation [FMD]) using generalized estimating equations. Participants (34 females; age, 32.1 +/- 9.6 years) had normal blood pressures (107.8 +/- 13.3/70.2 +/- 9.4 mm Hg), FMD (7.4 +/- 2.8%), as well as sleep and heart rate variability parameters. Mean 7-day outdoor-ambient (4.6 +/- 9.7 degrees C) differed from personal-level temperature exposures (22.0 +/- 3.0 degrees C). Colder outdoor ambient temperatures (per -10 degrees C) over the previous 1-6 days (rolling averages) were associated with decreases in FMD: -0.57% (95% confidence interval [CI]: -1.14% to 0.01%, P = .055) to -0.62% (95% CI: -1.07% to -0.18%, P = .006). However, a 10 degrees C decrease in personal-level temperature during the prior 24 hours was associated with a greater decrement in FMD: -2.44% (95% CI: -4.74% to -0.13%, P = .038). Both were also linearly related to FMD during all seasons and without a threshold temperature. Other end points were not significantly related to either temperature level in this study. Short-term exposures to colder environmental temperatures reduced endothelial-dependent vasodilatation, supporting the epidemiologic associations with heightened cardiovascular risk. We show here for the first time that temperature exposures characterized at the personal level may be more robust predictors of endothelial function than outdoor ambient levels. PMID- 28989071 TI - Air pollution and arterial hypertension. A new risk factor is in the air. AB - Air pollution is one of the greatest environmental threats and has been implicated for several adverse cardiovascular effects including arterial hypertension (HTN). However, the exact relationship between air pollution exposure and HTN is still unclear. Air contamination provokes oxidative stress, systemic inflammation, and autonomic nervous system imbalance that subsequently induce endothelial dysfunction and vasoconstriction leading to increased blood pressure. The aim of this review was to describe the potential mechanisms by which air pollution contributes to HTN and to summarize the consequences of short and long-term exposure. PMID- 28989072 TI - Pentoxifylline treatment enhances antihypertensive activity of captopril through hemorheological improvement in spontaneously hypertensive rats during development of arterial hypertension. AB - The rheological properties of blood play a significant role in the onset and progression of arterial hypertension. The aim of our work was to evaluate the effect of the angiotensin-converting enzyme inhibitor captopril (20 mg/kg/d), pentoxifylline (PTX; 100 mg/kg/d), and the combination of captopril + PTX (20 + 100 mg/kg/d) on the hemodynamic and hemorheological parameters in spontaneously hypertensive rats (SHRs) during the development of arterial hypertension. In the group of animals that received captopril, the mean arterial pressure (MAP) was significantly lower by 30% due to a decrease in cardiac output of 23% and in total peripheral resistance (TPR) of 26% compared with the control group, whereas blood viscosity did not change significantly. PTX-treated SHRs had significantly lower MAP and TPR (by 19% and 31%, respectively) and blood viscosity (by 4%-6%) and a higher erythrocyte deformability index (by 1.5%-2%) than the control group. In the group of animals that received captopril + PTX, MAP and TPR were significantly lower, by 41% and 46%, than those in the control group, and by 16% and 27% than those in the captopril group. The combination of the angiotensin converting enzyme inhibitor captopril and the hemorheological agent PTX, affecting various systems that are involved in blood pressure regulation, exhibits synergism and prevents an increase in arterial blood pressure during the development of arterial hypertension in SHRs (ie, from 5 to 11 weeks of life). PMID- 28989073 TI - Psychological Features and Their Relationship to Movement-Based Subgroups in People Living With Low Back Pain. AB - OBJECTIVE: To determine the distribution of higher psychological risk features within movement-based subgroups for people with low back pain (LBP). DESIGN: Cross-sectional observational study. SETTING: Participants were recruited from physiotherapy clinics and community advertisements. Measures were collected at a university outpatient-based physiotherapy clinic. PARTICIPANTS: People (N=102) seeking treatment for LBP. INTERVENTIONS: Participants were subgrouped according to 3 classification schemes: Mechanical Diagnosis and Treatment (MDT), Treatment Based Classification (TBC), and O'Sullivan Classification (OSC). MAIN OUTCOME MEASURES: Questionnaires were used to categorize low-, medium-, and high-risk features based on depression, anxiety, and stress (Depression, Anxiety, and Stress Scale-21 Items); fear avoidance (Fear-Avoidance Beliefs Questionnaire); catastrophizing and coping (Pain-Related Self-Symptoms Scale); and self-efficacy (Pain Self-Efficacy Questionnaire). Psychological risk profiles were compared between movement-based subgroups within each scheme. RESULTS: Scores across all questionnaires revealed that most patients had low psychological risk profiles, but there were instances of higher (range, 1%-25%) risk profiles within questionnaire components. The small proportion of individuals with higher psychological risk scores were distributed between subgroups across TBC, MDT, and OSC schemes. CONCLUSIONS: Movement-based subgrouping alone cannot inform on individuals with higher psychological risk features. PMID- 28989074 TI - Safety of Active Rehabilitation for Persistent Symptoms After Pediatric Sport Related Concussion: A Randomized Controlled Trial. AB - OBJECTIVES: To examine the safety and tolerability of an active rehabilitation program for adolescents who are slow to recover from a sport-related concussion, and secondarily to estimate the treatment effect for this intervention. DESIGN: Single-site, parallel, open-label, randomized controlled trial comparing treatment as usual (TAU) to TAU plus active rehabilitation. SETTING: Outpatient concussion clinic. PARTICIPANTS: Adolescents (N=19) aged 12 to 18 years with postconcussion symptoms lasting >=1 month after a sports-related concussion. INTERVENTIONS: TAU consisted of symptom management and return-to-play advice, return-to-school facilitation, and physiatry consultation. The active rehabilitation program involved in-clinic subsymptom threshold aerobic training, coordination exercises, and visualization and imagery techniques with a physiotherapist (mean, 3.4 sessions) as well as a home exercise program, over 6 weeks. MAIN OUTCOME MEASURES: A blinded assessor systematically monitored for predetermined adverse events in weekly telephone calls over the 6-week intervention period. The treating physiotherapist also recorded in-clinic symptom exacerbations during aerobic training. The Post-Concussion Symptom Scale was the primary efficacy outcome. RESULTS: Nineteen participants were randomized, and none dropped out of the study. Of the 12 adverse events detected (6 in each group), 10 were symptom exacerbations from 1 weekly telephone assessment to the next, and 2 were emergency department visits. Four adverse events were referred to an external safety committee and deemed unrelated to the study procedures. In clinic symptom exacerbations occurred in 30% (9/30) of aerobic training sessions, but resolved within 24 hours in all instances. In linear mixed modeling, active rehabilitation was associated with a greater reduction on the Post-Concussion Symptom Scale than TAU only. CONCLUSIONS: The results support the safety, tolerability, and potential efficacy of active rehabilitation for adolescents with persistent postconcussion symptoms. PMID- 28989075 TI - Development of a Social Functioning Assessment Using Computerized Adaptive Testing for Patients With Stroke. AB - OBJECTIVE: To develop a computerized adaptive test of social functioning (Social CAT) for patients with stroke. DESIGN: This study contained 2 phases. First, a unidimensional item bank was formed using social-related items with sufficient item fit (ie, infit and outfit mean square [MNSQ]). The social-related items were selected from 3 commonly used patient-reported quality-of-life measures. Items with differential item functioning (DIF) of sex were deleted. Second, we performed simulations to determine the best set of stopping rules with both high reliability and efficiency. The participants' responses to the items were extracted from a previous study. SETTING: Rehabilitation wards and departments of rehabilitation/neurology of 5 general hospitals. PARTICIPANTS: Patients (N=263) with stroke (47.1% were inpatients). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Social-CAT. RESULTS: The unidimensionality of the 24 selected items was supported (infit and outfit MNSQs =0.8-1.2). One item had DIF of sex and was deleted. The item bank was composed of the remaining 23 items. With the best set of stopping rules (person reliability >=.90 or limited reliability increased <=.001), the Social-CAT used on average 10 items to achieve sufficient reliability (average person reliability =.88; 81.0% of the patients with reliability >=.90). CONCLUSIONS: The Social-CAT appears to be a unidimensional measure with acceptable reliability and efficiency, and it could be useful for both clinicians and patients in time-pressed clinical settings. PMID- 28989076 TI - National Institute on Disability, Independent Living, and Rehabilitation Research Burn Model System: Review of Program and Database. AB - The Burn Model System (BMS) centers program was created in 1994 to evaluate the long-term outcomes of burn injuries. As part of this multicenter program, a comprehensive longitudinal database was developed to facilitate the study of a number of functional and psychosocial outcomes after burn injury. In this article, we provide an overview of the data collection procedures, measures selection process, and an overview of the participant data collected between 1994 and 2016. Surveys were administered during hospitalization and at 6, 12, and 24 months after discharge, and in the most recent funding cycle, data collection at every 5 years postinjury was added. More than 7200 people with burn injury were eligible to participate in the BMS National Longitudinal Database. Of these, >5900 (82%) were alive at discharge and consented to follow-up data collection. The BMS National Longitudinal Database represents a large sample of people with burn injury, including information on demographic characteristics, injury characteristics, and health outcomes. The database is publicly available and can be used to examine the effect of burn injury on long-term outcomes. PMID- 28989077 TI - Comparison of efficiencies of selected sample extraction techniques for the analysis of selected antiretroviral drugs in human plasma using LC-MS. AB - INTRODUCTION: Sample preparation in bio analytical chemistry poses a challenge because it can be compound dependent. We compared six sample extraction techniques i.e. QuEChERS (Q), liquid extraction (LE), protein precipitation (PPT), Q-PPT, Q-LE and LE-PPT for the extraction of antiretroviral drugs emtricitabine, tenofovir, efavirenz, lopinavir and rotinavir in human blood plasma. METHOD: A multiple reaction monitoring liquid chromatography- tandem mass spectrometry method for the determination of the same antiretroviral drugs developed and validated in this laboratory was used. Comparisons were based on the efficiencies of extraction, the precisions and accuracies. Using United States Food and Drug Administration guidelines, analytical performance characteristics i.e. limits of detection, lower limits of quantification and upper limits of quantification were also compared. RESULTS: The percent mean recoveries ranged between 68.8 and 81.2% for single modes and 52.4-70.5% for mixed mode techniques. The precisions of all the extraction techniques were within the Using United States Food and Drug Administration guidelines acceptable range of <15% at all concentration levels for all analytes. Accuracy ranged between 8.73 and 65.94% for single mode techniques and between 21.73 and 51.59% for mixed mode techniques. DISCUSSION: The mixed modes gave slightly lower recoveries but Q-LE compared well with the single modes at slightly higher spike levels. Limits of detection for all the six sample preparation techniques fell below the clinically relevant therapeutic range of approximately 3-8ppm. Therefore all techniques can be employed for routine therapeutic drug monitoring studies. PMID- 28989078 TI - Effects of G-quadruplex topology on translational inhibition by tRNA fragments in mammalian and plant systems in vitro. AB - The folding of tRNA fragments (tRFs) into G-quadruplex structures and the implications of G-quadruplexes in translational inhibition have been studied mainly in mammalian systems. To increase our knowledge of these phenomena, we determined the influence of human and plant tRFs and model G-quadruplexes on translation in rabbit reticulocyte lysate and wheat germ extract. The efficiency of translational inhibition in the mammalian system was strongly associated with the type of G-quadruplex topology. In the plant system, the ability of a small RNA to adopt the G-quadruplex conformation was not sufficient to repress translation, indicating the importance of other structural determinants. PMID- 28989079 TI - Impact of aging on distribution of IgA+ and IgG+ cells in aggregated lymphoid nodules area in abomasum of Bactrian camels (Camelus bactrianus). AB - The aggregated lymphoid nodules area (ALNA) in the abomasum is a special organized lymphoid tissue discovered only in Bactrian camels at present. This study aimed to explore the impact of aging on distribution of IgA+ and IgG+ cells in ALNA in abomasum of Bactrian camels. Twenty-four Alashan Bactrian camels were divided into the following four age groups: young (1-2years), pubertal (3 5years), middle-aged (6-16years) and old (17-20years). IgA+ and IgG+ cells in the lamina propria of ALNA were observed and analyzed using immunohistochemical and statistical techniques. The results showed that, in ALNA, the distribution of IgA+ and IgG+ cells were diffuse, and only a few were in subepithelium dome (SED) and most of them in non-SED. Meanwhile, there were significantly more IgA+ cells than IgG+ cells in SED from the young to the middle aged group, but which reversed in old group (P<0.05). However, the aging significantly decreased the densities of IgA+ and IgG+ cells populations in non-SED (P<0.05); in SED, there were no significant differences between the densities of IgA+ and IgG+ cells, but which were both significantly lower in old group than those in young group (P<0.05). The results demonstrated that, in mucosal effector sites, the aging significantly decreased the densities of IgA+ and IgG+ cells populations and impacted on the defense barriers formed by IgA and IgG, but had no impact on the scattered characteristics. In inductive sites, the aging dramatically declined their densities, and they should have close relationships with immune memory. These findings lay the foundation for further researching the mucosal immune disorder or decline caused by aging, and especially underscore the importance of researching the impact of aging on the relationship between IgA+ and IgG+ cells populations and the microbiota colonized in abomasum of Bactrian camels. PMID- 28989080 TI - Non-clinical efficacy-related studies for human medicines: An overview and retrospective analysis of data for a group of approved medicines. AB - The lack of efficacy is a major cause of medicine's development failure at the clinical phase, which may lead to question, among other aspects, the translation of the non-clinical data into humans. The objectives of the work here presented were (i) to get an overview (based on public assessment reports) of the nature of the non-clinical efficacy-related studies presented to the regulatory authorities at the marketing authorization application's stage for a group of approved anticancer human medicines (15 in total) and (ii) to conduct a retrospective analysis of such studies in terms of any identified insufficiencies and consistency with the current regulatory non-clinical guidelines. Each medicine has been tested in a number of in vitro assays and animal studies, which, all together, are judged to be capable of providing information on the activity of the active substance and demonstrating an anti-tumour effect, as well as to be generally consistent with the available, although limited detailed, guidance. In spite of this, some aspects were identified which could have a potential impact on the translation on non-clinical data into humans, namely, apparent insufficiencies in terms of animal model/human bridging data/knowledge and in vivo data on pharmacokinetics/pharmacodynamics relationships. PMID- 28989081 TI - Assessment of tobacco heating product THP1.0. Part 1: Series introduction. AB - We have recently developed a Tobacco Heating Product (THP) comprising an electrical heating device, commercially known as GloTM, and consumable tobacco rods, commercially known as Kent NeostiksTM. We refer to this system as THP1.0; Bright tobacco-flavoured variant THP1.0(T), or THP1.0(M) Menthol-flavoured variant. In this issue, we present a series of seven pre-clinical studies conducted on THP1.0,covering the following aspects of its design, development, safety and toxicological assessment, and a paper on placing THPs on an emissions continuum. PMID- 28989082 TI - Assessment of tobacco heating product THP1.0. Part 4: Characterisation of indoor air quality and odour. AB - The tobacco heating product THP1.0, which heats but does not burn tobacco, was tested as part of a modified-risk tobacco product assessment framework for its impacts on indoor air quality and residual tobacco smoke odour. THP1.0 heats the tobacco to less than 240 degrees C +/- 5 degrees C during puffs. An environmentally controlled room was used to simulate ventilation conditions corresponding to residential, office and hospitality environments. An analysis of known tobacco smoke constituents, included CO, CO2, NO, NO2, nicotine, glycerol, 3-ethenyl pyridine, sixteen polycyclic aromatic hydrocarbons, eight volatile organic compounds, four carbonyls, four tobacco-specific nitrosamines and total aerosol particulate matter. Significant emissions reductions in comparison to conventional cigarettes were measured for THP1.0. Levels of nicotine, acetaldehyde, formaldehyde and particulate matter emitted from THP1.0 exceeded ambient air measurements, but were more than 90% reduced relative to cigarette smoke emissions within the laboratory conditions defined Residual tobacco smoke odour was assessed by trained sensory panels after exposure of cloth, hair and skin to both mainstream and environmental emissions from the test products. Residual tobacco smoke odour was significantly lower from THP1.0 than from a conventional cigarette. These data show that using THP1.0 has the potential to result in considerably reduced environmental emissions that affect indoor air quality relative to conventional cigarettes. PMID- 28989083 TI - Resveratrol activation of AMPK-dependent pathways is neuroprotective in human neural stem cells against amyloid-beta-induced inflammation and oxidative stress. AB - Alzheimer's disease (AD) is a neurodegenerative disorder with progressive memory loss resulting in dementia. Amyloid-beta (Abeta) peptides play a critical role in the pathogenesis of this disease, and are thought to promote inflammation and oxidative stress leading to neurodegeneration in the neocortex and hippocampus of the AD brains. AMP-activated protein kinase (AMPK) is a master regulator of cellular energy homeostasis, and cell survival in response to inflammation and oxidative stress. However, the neuroprotective mechanisms by which AMPK achieves these beneficial effects in human neural stem cells (hNSCs) exposed to Abeta is still not well understood. Resveratrol is a potent activator of AMPK suggesting it may have therapeutic potential against AD. Therefore, we will test the hypothesis that the AMPK activator resveratrol protects against Abeta mediated neuronal impairment (inflammation and oxidative stress) in hNSCs. Here, Abeta treated hNSCs had significantly decreased cell viability that correlated with increased TNF-alpha and IL-1beta inflammatory cytokine expression. Co-treatment with resveratrol significantly abrogated the Abeta-mediated effects in hNSCs, and was effectively blocked by the addition of the AMPK-specific antagonist (Compound C). These results suggest the neuroprotective effects of resveratrol are mediated by an AMPK-dependent pathway. In addition, resveratrol rescued the transcript expression levels of inhibitory kappa B kinase (IKK) in Abeta-treated hNSCs. NF kappaB is a transcription factor with a key role in the expression of a variety of genes involved in inflammatory responses. Resveratrol prevented the Abeta mediated increases in NF-kappaB mRNA and protein levels, and its nuclear translocation in hNSCs. Co-treatment with resveratrol also significantly restored iNOS and COX-2 levels in Abeta-treated hNSCs. Furthermore, hNSCs co-treated with resveratrol were significantly rescued from Abeta-induced oxidative stress, which correlated with reversal of the Abeta-induced mRNA decrease in oxidative defense genes (SOD-1, NRF2, Gpx1, Catalase, GSH and HO-1). Taken together, these novel findings show that activation of AMPK-dependent signaling by resveratrol rescues Abeta-mediated neurotoxicity in hNSCs, and provides evidence supporting a neuroprotective role for AMPK activating drugs in Abeta-related diseases such as AD. PMID- 28989084 TI - Heterogeneity of atherosclerotic plaque macrophage origin, phenotype and functions: Implications for treatment. AB - Macrophages are key players in atherosclerotic lesions, regulating the local inflammatory milieu and plaque stability by the secretion of many inflammatory molecules, growth factors and cytokines. Monocytes have long been considered to be the main source of plaque macrophages. However, recent findings provide evidence for proliferation of local macrophages or transdifferentiation from other vascular cells as alternative sources. Recent years of research focused on the further identification and characterisation of macrophage phenotypes and functions. In this review we describe the advances in our understanding of monocyte and macrophage heterogeneity and its implications for specific therapeutic interventions, aiming to reduce the ever growing significant risk of cardiovascular events without any detrimental side effects on the patient's immune response. PMID- 28989085 TI - Ferulic acid relaxed rat aortic, small mesenteric and coronary arteries by blocking voltage-gated calcium channel and calcium desensitization via dephosphorylation of ERK1/2 and MYPT1. AB - Ferulic acid, a natural ingredient presents in several Chinese Materia Medica such as Radix Angelicae Sinensis, has been identified as an important multifunctional and physiologically active small molecule. However, its pharmacological activity in different blood vessel types and underlying mechanisms are unclear. The present study was to investigate the vascular reactivity and the possible action mechanism of FA on aorta, small mesenteric arteries and coronary arteries isolated from Wistar rats. We found FA dose dependently relieved the contraction of aorta, small mesenteric arteries and coronary arteries induced by different contractors, U46619, phenylephrine (Phe) and KCl. The relaxant effect of FA was not affected by L-NAME (eNOS inhibitor), ODQ (soluble guanylate cyclase inhibitor), and mechanical removal of endothelium in thoracic aortas. The contraction caused by 60mM KCl (60K) was concentration dependently hindered by FA pretreatment in all three types of arteries. In Ca2+ free 60K solution, FA weakened Ca2+-related contraction in a concentration dependent manner. And FA relaxed both fluoride and phorbol ester which were PKC, ERK and Rho-kinase activators induced contraction in aortic rings with or without Ca2+ in krebs solution. Western blotting experiments in A7r5 cells revealed that FA inhibited calcium sensitization via dephosphorylation of ERK1/2 and MYPT1. Furthermore, the relaxation effect of FA was attenuated by verapamil (calcium channel blocker), ERK inhibitor, and fasudil (ROCK inhibitor). These results provide evidence that FA exhibits endothelium-independent vascular relaxant effect in different types of arteries. The molecular mechanism of vasorelaxation activity of FA probably involved calcium channel inhibition and calcium desensitization. PMID- 28989087 TI - Catanionic systems in nanotherapeutics - Biophysical aspects and novel trends in drug delivery applications. AB - Mixtures of surfactants can result in formation of various structures like micelles, vesicles and inverted micelles. Catanionic vesicular systems are preferred on account of their ease of formation and thermodynamic stability. Furthermore, their charge and surfactant properties render them as useful vehicles for DNA delivery and cytotoxic compounds. They suffer from disadvantages of being leaky and yielding low encapsulation efficiencies which are averse to drug delivery purposes. Extensive efforts are being undertaken to overcome these barriers and render these vesicles amenable to spatial placement and temporal delivery of drugs. This manuscript addresses diverse aspects of catanionic vesicles including their formation, fabrication and stability. The manuscript focuses further on applications of catanionic vesicles in nanodrug delivery. Novel trends in the field of catanionics with respect to bio-compatibility and novel technologies developed using these systems have also been reviewed. An attempt has been made to compile catanionic systems reported in literature detailing surfactants and therapeutic agents employed to aid understanding and yield information of various facets that drive fabrication and potential utility of these systems in therapeutics. PMID- 28989086 TI - Reported gastroparesis in adults with type 1 diabetes (T1D) from the T1D Exchange clinic registry. AB - OBJECTIVE: To better understand the prevalence and impact of gastroparesis in the T1D Exchange clinic registry database. METHODS: The analysis included 7107 adult participants with T1D across 45 sites (median age 46years. and median duration 24years). Linear and logistic regression models were used to assess the association of gastroparesis vs. no gastroparesis (obtained from medical record) with demographic characteristics, glycemic control and diabetes complications. RESULTS: Among 7107 registry participants, 340 (4.8%) had a clinical diagnosis of gastroparesis. Females were more likely to have gastroparesis compared with males (5.8% vs. 3.5%, P<0.001). Participants with gastroparesis compared with those without gastroparesis were older (median age 49.4 vs. 45.3years, P<0.001), had a longer duration of T1D (median duration 32 vs. 23years, P<0.001), higher mean HbA1c (8.1% vs. 7.7% [65 vs. 61mmol/mol], P<0.001), more frequent severe hypoglycemia (25% vs. 11% with >=1 event in the past 12months, P<0.001), lower socio-economic status, less likely to be using CGM and insulin pump and greater prevalence of microvascular and neuropathic complications than participants without gastroparesis. CONCLUSION: Gastroparesis is associated with higher risk of severe hypoglycemia despite higher HbA1c levels than in T1D patients without gastroparesis. The increased presence of multiple long-term complications and overall poor glycemic control in these subjects emphasizes the need to establish diagnostic protocols for earlier diagnosis, achieve tighter glycemic control with more extensive use of insulin pumps and continuous glucose monitoring, and the need for wider availability of medical therapies for treatment of diabetic gastroparesis. PMID- 28989088 TI - The Magnesium Transporter MGT10 Is Essential for Chloroplast Development and Photosynthesis in Arabidopsis thaliana. PMID- 28989089 TI - Fungal mitochondrial oxygen consumption induces the growth of strict anaerobic bacteria. AB - Fungi are commonly encountered as part of a healthy oral ecosystem. Candida albicans is the most often observed and investigated fungal species in the oral cavity. The role of fungi in the oral ecosystem has remained enigmatic for decades. Recently, it was shown that C. albicans, in vitro, influences the bacterial composition of young oral biofilms, indicating it possibly plays a role in increasing diversity in the oral ecosystem. C. albicans favored growth of strictly anaerobic species under aerobic culture conditions. In the present study, the role of mitochondrial respiration, as mechanism by which C. albicans modifies its environment, was investigated. Using oxygen sensors, a rapid depletion of dissolved oxygen (dO2) was observed. This decrease was not C. albicans specific as several non-albicans Candida species showed similar oxygen consumption. Heat inactivation as well as addition of the specific mitochondrial respiration inhibitor Antimycin A inhibited depletion of dO2. Using 16S rDNA sequencing, it is shown that mitochondrial activity, more than physical presence of C. albicans is responsible for inducing growth of strictly anaerobic oral bacteria in aerobic growth conditions. The described mechanism of dO2 depletion may be a general mechanism by which fungi modulate their direct environment. PMID- 28989090 TI - Different IgM+ B cell subpopulations residing within the peritoneal cavity of vaccinated rainbow trout are differently regulated by BAFF. AB - In teleost fish, IgM+ B cells are one of the main responders against inflammatory stimuli in the peritoneal cavity, as IgM+ B cells dominate the peritoneum after intraperitoneal stimulation, also increasing the levels of secreted IgM. BAFF, a cytokine known to play a major role in B cell biology, has been shown to be up regulated along with its receptors in the peritoneum of rainbow trout upon antigenic exposure, however, the regulatory mechanisms underneath this response remain unclear. In this study, we have identified two different IgM+ B cell types residing in the peritoneal cavity of previously vaccinated rainbow trout (Oncorhynchus mykiss): IgD+IgMhiMHCIIhi cells, resembling naive B cells, and IgD IgMloMHCIIlo cells, resembling antibody-secreting cells. Based on their membrane IgM levels, these cell types were named IgMhi and IgMlo B cells, respectively. As each of these B cell populations showed a distinct expression pattern for the different BAFF receptors, we studied the effect of BAFF individually on each cell subset. Recombinant BAFF promoted the survival of IgMlo but not IgMhi B cells in vitro, resulting in increased levels of IgM-secreting cells. In contrast, BAFF increased the levels of membrane MHC II only on IgMhi B cells, suggesting different functions on these B cell subsets. Moreover, we also showed that peritoneal IgMhi B cells expressed BAFF at levels comparable to those seen on myeloid cells. These results point to BAFF as a main regulator of B cell homeostasis in the peritoneal cavity, suggesting that this cytokine can trigger different signals on different peritoneal B cell subsets in a specific manner. PMID- 28989091 TI - More than just antibodies: Protective mechanisms of a mucosal vaccine against fish pathogen Flavobacterium columnare. AB - A recently developed attenuated vaccine for Flavobacterium columnare has been demonstrated to provide superior protection for channel catfish, Ictalurus punctatus, against genetically diverse columnaris isolates. We were interested in examining the mechanisms of this protection by comparing transcriptional responses to F. columnare challenge in vaccinated and unvaccinated juvenile catfish. Accordingly, 58 day old fingerling catfish (28 days post-vaccination or unvaccinated control) were challenged with a highly virulent F. columnare isolate (BGSF-27) and gill tissues collected pre-challenge (0 h), and 1 h and 2 h post infection, time points previously demonstrated to be critical in early host pathogen interactions. Following RNA-sequencing and transcriptome assembly, differential expression (DE) analysis within and between treatments revealed several patterns and pathways potentially underlying improved survival of vaccinated fish. Most striking was a pattern of dramatically higher basal expression of an array of neuropeptides (e.g. somatostatin), hormones, complement factors, and proteases at 0 h in vaccinated fish. Previous studies indicate these are likely the preformed mediators of neuroendocrine cells and/or eosinophilic granular (mast-like) cells within the fish gill. Following challenge, these elements fell to almost undetectable levels (>100-fold downregulated) by 1 h in vaccinated fish, suggesting their rapid release and/or cessation of synthesis following degranulation. Concomitantly, levels of pro-inflammatory cytokines (IL 1b, IL-8, IL-17) were induced in unvaccinated fish. In contrast, in vaccinated catfish, we observed widespread induction of genes needed for collagen deposition and tissue remodeling. Taken together, our results indicate an important component of vaccine protection in fish mucosal tissues may be the sensitization, proliferation and arming of resident secretory cells in the period between primary and secondary challenge. PMID- 28989092 TI - Advanced liver fibrosis but not steatosis is independently associated with albuminuria in Chinese patients with type 2 diabetes. AB - BACKGROUND & AIMS: Increasing evidence suggests that non-alcoholic fatty liver disease (NAFLD) may be an independent risk factor for chronic kidney disease (CKD). Given the high prevalence of NAFLD among patients with diabetes who are also at risk of CKD, we aimed to investigate the association between NAFLD and albuminuria, a marker commonly found in diabetic nephropathy. METHODS: This study included a cohort of Chinese patients with type 2 diabetes from the Hong Kong Diabetes Registry recruited between March 2013 and May 2014. Liver stiffness measurement (LSM), with probe-specific cut-offs, was used to detect advanced liver fibrosis. While controlled attenuation parameter (CAP) was used to assess liver steatosis using transient elastography. RESULTS: A total of 1,763 Chinese patients with type 2 diabetes were recruited in this analysis. The mean (standard deviation) age and duration of diabetes were 60.7 (11.5) years and 10.8 (8.5) years, respectively. The prevalence of albuminuria was higher in diabetic patients with liver steatosis and those with advanced fibrosis (no NAFLD vs. liver steatosis vs. advanced fibrosis: 41.4% vs. 46.2% vs. 64.2%, p <0.001). After adjustment for potential confounders including glycated hemoglobin, hypertension and body mass index, advanced fibrosis, but not liver steatosis, was associated with increased risk of albuminuria (odds ratio [OR] 1.52; 95% confidence interval [CI] 1.02-2.28; p = 0.039) in patients with eGFR >=60 ml/min/1.73 m2. The odds of albuminuria increased with greater severity of liver fibrosis in a dose dependent manner, with the highest odds observed in patients with LSM scores >=11.5 kPa assessed by M probe or >=11.0 kPa assessed by XL probe (adjusted OR 1.53; 95% CI 1.07-2.20; p = 0.021). CONCLUSIONS: Advanced liver fibrosis, but not steatosis, is independently associated with albuminuria in Chinese patients with type 2 diabetes. Attention should be paid to liver fibrosis in patients with obesity and type 2 diabetes complicated with albuminuria. LAY SUMMARY: In this study, we assessed the link between non-alcoholic fatty liver disease (NAFLD) and albuminuria in a cohort of 1,763 Chinese patients with type 2 diabetes. This study shows that advanced liver fibrosis, a severe form of NAFLD, was independently associated with increased risk of albuminuria. The risk of albuminuria increased with greater severity of liver fibrosis. PMID- 28989093 TI - Durability of hepatitis B surface antigen seroclearance in untreated and nucleos(t)ide analogue-treated patients. AB - BACKGROUND & AIMS: It is uncertain if nucleos(t)ide analogue (NA)-induced hepatitis B surface antigen (HBsAg) seroclearance is durable. We investigated the impact of hepatitis B surface antibody (anti-HBs) and duration of consolidation antiviral therapy on the durability of HBsAg seroclearance. METHODS: A territory wide cohort study was conducted using data from the Hospital Authority, Hong Kong. We identified all subjects with positive HBsAg between January 1, 2000 and August 31, 2016. NA use, liver biochemistries, serial HBsAg and anti-HBs results were retrieved. The primary endpoint was confirmed HBsAg seroclearance, defined least two negative HBsAg test results, with the last HBsAg test being negative in patients with chronic hepatitis B (CHB). RESULTS: A total of 4,080 CHB patients were included for analysis. In patients with spontaneous HBsAg seroclearance (n=3,563), 1,771 patients (49.7%) had confirmed HBsAg seroclearance and 75 patients (2.1%) had HBsAg seroreversion. In patients with NA-induced HBsAg seroclearance (n=475), 320 patients (67.4%) had confirmed HBsAg seroclearance and 14 patients (2.9%) had HBsAg seroreversion. The five-year cumulative probability of confirmed HBsAg seroclearance was comparable in patients with spontaneous and NA-induced HBsAg seroclearance (88.1% vs. 92.2%; Log-rank test, p=0.964); it was also similar in patients with or without anti-HBs in NA-treated patients (95.4% vs. 95.5%, Log-rank test, p=0.602). HBsAg seroreversion was only observed in 3 (2.0%) patients who had received consolidation therapy for 6-12months and none of those who had received it for >=12months. CONCLUSIONS: NA-induced HBsAg seroclearance is as durable as spontaneous HBsAg seroclearance. NA-treated patients may not need to have positive anti-HBs before stopping treatment. Longer consolidation NA treatment may result in more durable HBsAg seroclearance. LAY SUMMARY: We investigated 4,080 patients with hepatitis B surface antigen (HBsAg) seroclearance. HBsAg seroreversion occurred in 2.1% of patients with spontaneous and 2.9% of those with nucleos(t)ide analogues-induced HBsAg seroclearance. PMID- 28989094 TI - Impact of time to surgery in the outcome of patients with liver resection for BCLC 0-A stage hepatocellular carcinoma. AB - BACKGROUND & AIMS: The Barcelona Clinic Liver Cancer (BCLC) guidelines recommend resection for very early and early single hepatocellular carcinoma (HCC) patients. It is not known whether a delay in resection from the time of diagnosis (the time to surgery [TTS], i.e. the elapsed time from diagnosis to surgery) affects outcomes. We aim to evaluate the impact of TTS on recurrence and survival outcomes in patients with HCC. METHODS: All patients resected for BCLC stage 0-A single HCC from 2006 to 2016 were studied to evaluate the impact of TTS on recurrence rate, recurrence-free survival (RFS), transplantability following recurrence, and intention-to-treat overall survival (ITT-OS). Propensity score matching (PSM) was further performed to ensure comparability. RESULTS: The study population included 100 patients. Surgery was performed between 0.6 and 77 months after diagnosis (median TTS: three months; interquartile range: 1.8-4.6 months). There was no post-operative mortality. Compared to those with TTS <3 months, patients with TTS >=3 months (70% of these patients had TTS 3-6 months) had a higher post-operative morbidity (36% vs. 16%, p = 0.02), a similar tumor recurrence rate (32% vs. 32%, p = 1.00), RFS (37% vs. 48%, p = 0.42), transplantability following tumor recurrence (63% vs. 50%, p = 0.48), and five year ITT-OS (82% vs. 80%, p = 0.20). Similar results were observed after PSM. CONCLUSION: Patients with BCLC stage 0-A single HCC can undergo surgery with TTS >=3 months without impaired oncologic outcomes. An increase in the TTS within a safe range could allow time for proper evaluation before surgery, and ethical testing of new neoadjuvant treatments, aiming to reduce the high rate of tumor recurrence despite curative resection. LAY SUMMARY: A delay of >=3 months in time to resection after diagnosis in HCC patients meeting the European Association for the Study of Liver Disease/American Association for the Study of Liver Disease criteria for resection does not affect oncological and long-term outcomes compared to those with a delay to surgery of <3 months. PMID- 28989097 TI - Assessing the utility of transcriptome data for inferring phylogenetic relationships among coleoid cephalopods. AB - Historically, deep-level relationships within the molluscan class Cephalopoda (squids, cuttlefishes, octopods and their relatives) have remained elusive due in part to the considerable morphological diversity of extant taxa, a limited fossil record for species that lack a calcareous shell and difficulties in sampling open ocean taxa. Many conflicts identified by morphologists in the early 1900s remain unresolved today in spite of advances in morphological, molecular and analytical methods. In this study we assess the utility of transcriptome data for resolving cephalopod phylogeny, with special focus on the orders of Decapodiformes (open eye squids, bobtail squids, cuttlefishes and relatives). To do so, we took new and previously published transcriptome data and used a unique cephalopod core ortholog set to generate a dataset that was subjected to an array of filtering and analytical methods to assess the impacts of: taxon sampling, ortholog number, compositional and rate heterogeneity and incongruence across loci. Analyses indicated that datasets that maximized taxonomic coverage but included fewer orthologs were less stable than datasets that sacrificed taxon sampling to increase the number of orthologs. Clades recovered irrespective of dataset, filtering or analytical method included Octopodiformes (Vampyroteuthis infernalis + octopods), Decapodiformes (squids, cuttlefishes and their relatives), and orders Oegopsida (open-eyed squids) and Myopsida (e.g., loliginid squids). Ordinal-level relationships within Decapodiformes were the most susceptible to dataset perturbation, further emphasizing the challenges associated with uncovering relationships at deep nodes in the cephalopod tree of life. PMID- 28989096 TI - Exploiting 2A peptides to elicit potent neutralizing antibodies by a multi subunit herpesvirus glycoprotein complex. AB - Neutralizing antibodies (NAb) interfering with glycoprotein complex-mediated virus entry into host cells are thought to contribute to the protection against herpesvirus infection. However, using herpesvirus glycoprotein complexes as vaccine antigens can be complicated by the necessity of expressing multiple subunits simultaneously to allow efficient complex assembly and formation of conformational NAb epitopes. By using a novel bacterial artificial chromosome (BAC) clone of the clinically deployable Modified Vaccinia Ankara (MVA) vector and exploiting ribosomal skipping mediated by 2A peptides, MVA vectors were generated that expressed self-processing subunits of the human cytomegalovirus (HCMV) pentamer complex (PC) composed of gH, gL, UL128, UL130, and UL131A. These MVA vectors expressed 2A-linked HCMV PC subunits that were efficiently cleaved and transported to the cell surface as protein complexes forming conformational neutralizing epitopes. In addition, vaccination of mice by only two immunizations with these MVA vectors resulted in potent HCMV NAb responses that remained stable over a period of at least six months. This method of eliciting NAb by 2A-linked, self-processing HCMV PC subunits could contribute to develop a HCMV vaccine candidate and may serve as a template to facilitate the development of subunit vaccine strategies against other herpesviruses. PMID- 28989098 TI - Phenotypic evolution in marmoset and tamarin monkeys (Cebidae, Callitrichinae) and a revised genus-level classification. AB - Marmosets and tamarins (Cebidae, Callitrichinae) constitute the most species-rich subfamily of New World monkeys and one of the most diverse phenotypically. Despite the profusion of molecular phylogenies of the group, the evolution of phenotypic characters under the rapidly-emerging consensual phylogeny of the subfamily has been little studied, resulting in taxonomic proposals that have limited support from other datasets. We examined the evolution of 18 phenotypic traits (5 continuous and 13 discrete), including pelage, skull, dentition, postcrania, life-history and vocalization variables in a robust molecular phylogeny of marmoset and tamarin monkeys, quantifying their phylogenetic signal and correlations among some of the traits. At the family level, our resulting topology supports owl monkeys (Aotinae) as sister group of Callitrichinae. The topology of the callitrichine tree was congruent with previous studies except for the position of the midas group of Saguinus tamarins, which placement as sister of the bicolor group did not receive significant statistical support in both Maximum Parsimony and Bayesian Inference analyses. Our results showed that the highest value of phylogenetic signal among continuous traits was displayed by the long call character and the lowest was exhibited in the home range, intermediate values were found in characters related to osteology and skull size. Among discrete traits, pelage and osteology had similar phylogenetic signal. Based on genetic, osteological, pelage and vocalization data, we present an updated genus level taxonomy of Callitrichinae, which recognizes six genera in the subfamily: Callimico, Callithrix, Cebuella, Mico, Leontopithecus and Saguinus. To reflect their phenotypic distinctiveness and to avoid the use of the informal "species group", we subdivided Saguinus in the subgenera Leontocebus, Saguinus and Tamarinus (revalidated here). PMID- 28989095 TI - Risk factors and prevention of hepatocellular carcinoma in the era of precision medicine. AB - Patients who develop chronic fibrotic liver disease, caused by viral or metabolic aetiologies, are at a high risk of developing hepatocellular carcinoma (HCC). Even after complete HCC tumour resection or ablation, the carcinogenic tissue microenvironment in the remnant liver can give rise to recurrent de novo HCC tumours, which progress into incurable, advanced-stage disease in most patients. Thus, early detection and prevention of HCC development is, in principle, the most impactful strategy to improve patient prognosis. However, a "one-size-fits all" approach to HCC screening for early tumour detection, as recommended by clinical practice guidelines, is utilised in less than 20% of the target population, and the performance of screening modalities, including ultrasound and alpha-fetoprotein, is suboptimal. Furthermore, optimal screening strategies for emerging at-risk patient populations, such as those with chronic hepatitis C after viral cure, or those with non-cirrhotic, non-alcoholic fatty liver disease remain controversial. New HCC biomarkers and imaging modalities may improve the sensitivity and specificity of HCC detection. Clinical and molecular HCC risk scores will enable precise HCC risk prediction followed by tailoured HCC screening of individual patients, maximising cost-effectiveness and optimising allocation of limited medical resources. Several aetiology-specific and generic HCC chemoprevention strategies are evolving. Epidemiological and experimental studies have identified candidate chemoprevention targets and therapies, including statins, anti-diabetic drugs, and selective molecular targeted agents, although their clinical testing has been limited by the lengthy process of cancer development that requires long-term, costly studies. Individual HCC risk prediction is expected to overcome the challenge by enabling personalised chemoprevention, targeting high-risk patients for precision HCC prevention and substantially improving the dismal prognosis of HCC. PMID- 28989100 TI - Pleiotropic genes in psychiatry: Calcium channels and the stress-related FKBP5 gene in antidepressant resistance. AB - A candidate gene and a genome-wide approach were combined to study the pharmacogenetics of antidepressant response and resistance. Investigated genes were selected on the basis of pleiotropic effect across psychiatric phenotypes in previous genome-wide association studies and involvement in antidepressant response. Three samples with major depressive disorder (total=671) were genotyped for 44 SNPs in 8 candidate genes (CACNA1C, CACNB2, ANK3, GRM7, TCF4, ITIH3, SYNE1, FKBP5). Phenotypes were response/remission after 4weeks of treatment and treatment-resistant depression (TRD). Genome-wide data from STAR*D were used to replicate findings for response/remission (n=1409) and TRD (n=620). Pathways including the most promising candidate genes were investigated in STAR*D for involvement in TRD. FKBP5 polymorphisms showed replicated but nominal associations with response, remission or TRD. CACNA1C rs1006737 and rs10848635 were the only polymorphisms that survived multiple-testing correction. In STAR*D the best pathway associated with TRD included CACNA1C (GO:0006942, permutated p=0.15). Machine learning models showed that independent SNPs in this pathway predicted TRD with a mean sensitivity of 0.83 and specificity of 0.56 after 10 fold cross validation repeated 100 times. FKBP5 polymorphisms appear good candidates for inclusion in antidepressant pharmacogenetic tests. Pathways including the CACNA1C gene may be involved in TRD and they may provide the base for developing multi-marker predictors of TRD. PMID- 28989101 TI - Securing extraocular muscles in strabismus surgery: laboratory analysis of biomechanical parameters related to the suture. AB - PURPOSE: To investigate the tensile properties of several components used to secure extraocular muscle to sclera in strabismus surgery to determine potential failure points. METHODS: A digital force gauge measured the tensile strength of intact or damaged 6-0 Vicryl suture (Ethicon, Somerville, NJ), as well as threads tied in a 2-1-1 or 2-1-1-1 surgeon's knot configuration. Human sclera was used to test the resistance to drag of knotted and unknotted 6-0 Vicryl suture thread through partial thickness sclera. Mean values were compared using a t test. RESULTS: The mean tensile strength of 6-0 Vicryl suture was 623.5 g, but it was markedly reduced by damage from the needle (P < 0.0001) or ophthalmic needle holder (P < 0.0001). The 2-1-1 knots broke at a mean force of 307.6 g, compared with 292.8 g for 2-1-1-1 knots (P = 0.84). Drag through a 2 mm scleral tunnel was 4.6 g, compared to 13.6 g for a 4 mm tunnel (P = 0.011). The force required to pull a knotted suture through a 4 mm scleral tunnel was 254 g for a 2-1-1 knot and 367 g for a 2-1-1-1 knot (P < 0.015). CONCLUSIONS: Although 6-0 Vicryl possesses adequate tensile strength for muscle fixation, thread damage from a needle or needle holder may cause serious losses in tensile strength. Knot breaking strength is not significantly increased by adding a fourth throw. Frictional forces of the scleral tunnel are not sufficient to provide muscle stabilization, but the presence of a knot can provide substantial resistance to suture slip into the scleral tunnel. PMID- 28989102 TI - Comparative evaluation of electrospraying and lyophilization techniques on solid state properties of Erlotinib nanocrystals: Assessment of In-vitro cytotoxicity. AB - INTRODUCTION: Erlotinib is a well known FDA approved drug from category of tyrosine kinase inhibitors; used for the treatment of lung cancer. However its use is limited because of its poor water solubility. OBJECTIVE: The aim of present work was to improve solubility by developing a stable nanocrystal based drug delivery system of ERL with the aid of sodium lauryl sulfate as potential stabilizer and to carry out comparative evaluation of electrospraying and lyophilization as solidification techniques on its solid state properties. EXPERIMENTAL: Nanocrystal formulation was developed with antisolvent precipitation method having particle size, polydispersity index and zetapotential of 232.4+/-4.3nm, 0.162 and -9.82mV respectively. Further comparative evaluation of lyophilization and electrospraying was commenced as potential solidification techniques and solid powder matrix obtained from both the solidification techniques were compared in terms of size after re-dispersion (260+/-4.8 and 329+/-5.2nm respectively), particle morphology, surface area (0.984+/-0.11 and 0.341+/-0.05m2/g respectively), pore volume (0.0014 and 0.0009cc/g respectively), solid state of drug present and % drug release (~100% and ~78% respectively in 600min). In vitro cytotoxicity studies shared that obtained formulation was having reduced IC50 values in comparison to drug. Further intracellular reactive oxygen species production was found to be higher for formulation treated cells when compared to free drug. Overall developed formulation was found to be potential drug delivery system for lung cancer therapy. PMID- 28989103 TI - Antimalarial drug toxicities in patients with cutaneous lupus and dermatomyositis: A retrospective cohort study. AB - BACKGROUND: Although existing evidence demonstrates the efficacy of antimalarials for rheumatic skin disease, the safety of these medications, and particularly quinacrine, remains debated. OBJECTIVE: We investigated the toxicity risk associated with antimalarials in patients with cutaneous lupus erythematosus and dermatomyositis. METHODS: A total of 532 patients (mean age, 52.29 years; sample composition by sex, 85.15% female vs 14.85% male) were selected from 2 databases on cutaneous lupus erythematosus (69.92%) and dermatomyositis (30.08%). Details regarding treatment and toxicities were extracted and 5 treatment courses were defined (ie, hydroxychloroquine [HCQ], chloroquine [CQ], quinacrine [Q], HCQ-Q combination therapy [HCQ-Q], and CQ-Q combination therapy [CQ-Q]). The hazard ratio for each major toxicity was estimated by using the Cox proportional hazard model to compare the different treatments with HCQ. RESULTS: The most common toxicities included cutaneous eruption, gastrointestinal upset, mucocutaneous dyspigmentation, neurologic toxicity, and retinopathy. The hazards of cutaneous eruption, gastrointestinal upset, and neurologic toxicities were lower with HCQ-Q than with HCQ; however, this may represent selection bias. Although there was increased retinopathy risk with CQ and CQ-Q versus with HCQ, retinopathy was not seen with Q. LIMITATIONS: Retrospective analysis. CONCLUSIONS: With the exception of retinopathy, which was not seen with Q, the risks for other toxicities associated with Q monotherapy or combination treatment were not significantly different from those with HCQ. PMID- 28989105 TI - Comparison of cyclic and continuous 308-nm excimer laser treatments for vitiligo: A randomized controlled noninferiority trial. PMID- 28989104 TI - Epidemiology of malignant cutaneous granular cell tumors: A US population-based cohort analysis using the Surveillance, Epidemiology, and End Results (SEER) database. AB - BACKGROUND: Malignant cutaneous granular cell tumors (mcGCTs) are rare and associated with substantial morbidity and mortality. The literature includes single-institution studies. OBJECTIVE: To examine the incidence, secondary malignancies, treatment, overall survival, and disease-specific survival (DSS) of patients with mcGCT. METHODS: A population-based cohort analysis was conducted in the Surveillance, Epidemiology, and End Results database from 1973 to 2013 for patients with a diagnosis of mcGCT. Risk-adjusted associations between overall survival/DSS and patient characteristics and treatment modalities were assessed by Cox proportional hazard regression. Quantile regression was used to determine median survival times. RESULTS: The 5-year DSS rate was 62.8%. Patients demonstrated an increased risk for renal and pancreatic cancers. In risk-adjusted models, male sex (hazard ratio [HR], 0.21; 95% confidence interval [CI], 0.06 0.82; P = .02), advanced cancer stage (HR, 2.29; 95% CI, 1.40-3.72; P < .01), and surgical resection (HR, 0.06; 95% CI, 0.01-0.59; P = .02) predicted DSS. Median survival time in years increased for males (1.39), earlier stage (0.60), and surgical intervention (5.34). LIMITATIONS: Absent or incorrect reporting in retrospective Surveillance, Epidemiology, and End Results data is possible. The database is more likely to include academic centers. Some subanalyses may be underpowered because of the limited sample size for a rare cancer. CONCLUSIONS: Our study presents an in-depth assessment of factors that identify high-risk patients. Residency in a nonmetro area, black race, female sex, and no surgical resection were each associated with poorer DSS. PMID- 28989106 TI - Demographic and health care service utilization by 4417 patients with hidradenitis suppurativa. AB - BACKGROUND: Data on the health care utilization of patients with hidradenitis suppurativa (HS) in primary care settings are scarce. OBJECTIVE: To investigate the health care service utilization of patients with HS. METHODS: In a cross sectional study, patients with HS were compared with 2 age- and sex-matched control groups-general population enrollees of Clalit Health Services and a group of patients with psoriasis. Health care services data included inpatient and outpatient community clinic visits and pharmacy claims for topical and systemic treatments. Multivariate analysis of the data for patients with HS and controls was performed. RESULTS: The study included 4417 patients with HS, 22,085 general population enrollees, and 4417 patients with psoriasis. On the basis of multivariate analyses, patients with HS had more annual dermatology clinic visits compared with the general population enrollees (odds ratio [OR], 6.49; 95% confidence interval [CI], 7.06-5.97) and patients with psoriasis (OR, 1.32; 95% CI, 1.44-1.21), more annual surgical clinic visits (OR, 3.78; 95% CI 3.28-4.36 and OR, 1.65; 95% CI, 1.42-1.91, respectively), and more hospitalizations (OR, 2.21; 95% CI, 1.89-2.56 and OR, 1.51; 95% CI, 1.28-1.78, respectively). LIMITATIONS: Underestimation of HS frequency was possible. CONCLUSIONS: The burden on health care systems due to patients with HS is greater than that due to patients with psoriasis and the general population. PMID- 28989108 TI - Novel uses of bilateral advancement flaps for tip defects on the nose: Part II. PMID- 28989107 TI - Azathioprine and risk of multiple keratinocyte cancers. PMID- 28989109 TI - Machine learning and melanoma: The future of screening. PMID- 28989099 TI - Astroglial correlates of neuropsychiatric disease: From astrocytopathy to astrogliosis. AB - Complex roles for astrocytes in health and disease continue to emerge, highlighting this class of cells as integral to function and dysfunction of the nervous system. In particular, escalating evidence strongly implicates a range of changes in astrocyte structure and function associated with neuropsychiatric diseases including major depressive disorder, schizophrenia, and addiction. These changes can range from astrocytopathy, degeneration, and loss of function, to astrogliosis and hypertrophy, and can be either adaptive or maladaptive. Evidence from the literature indicates a myriad of changes observed in astrocytes from both human postmortem studies as well as preclinical animal models, including changes in expression of glial fibrillary protein, as well as changes in astrocyte morphology and astrocyte-mediated regulation of synaptic function. In this review, we seek to provide a comprehensive assessment of these findings and consequently evidence for common themes regarding adaptations in astrocytes associated with neuropsychiatric disease. While results are mixed across conditions and models, general findings indicate decreased astrocyte cellular features and gene expression in depression, chronic stress and anxiety, but increased inflammation in schizophrenia. Changes also vary widely in response to different drugs of abuse, with evidence reflective of features of astrocytopathy to astrogliosis, varying across drug classes, route of administration and length of withdrawal. PMID- 28989110 TI - Novel uses of bilateral advancement flaps for tip defects on the nose: Part I. PMID- 28989111 TI - Efficacy and tolerance profile of thalidomide in cutaneous lupus erythematosus: A systematic review and meta-analysis. AB - BACKGROUND: Thalidomide has shown excellent results for severe cutaneous lupus erythematosus (CLE), but its prescription is limited by potentially severe adverse events. OBJECTIVE: To assess the overall rate of response to thalidomide in CLE with respect to CLE subtypes and the occurrence rate of relevant adverse events on the basis of previously published studies. METHODS: We performed a systematic review and meta-analysis of studies published in MEDLINE, Embase, and the Cochrane Library between 1965 and January 2017. The proportions of responders and rates of adverse events were extracted from individual studies and pooled using random effects or fixed models. RESULTS: Among 548 patients from 21 included studies, the overall rate of response to thalidomide was 90% (95% confidence interval [CI], 85-94), with similar response rates between CLE subtypes. Conversely, the pooled rate of thalidomide withdrawal related to adverse events was 24% (95% CI, 14-35) including confirmed peripheral neuropathy in 16% (95% CI, 9-25) and thromboembolic events in 2% (95% CI, 1-3). The pooled rate of relapse after thalidomide withdrawal was 71% (95% CI, 65-77) compared with 34% (95% CI, 25-44) with a maintenance dose. LIMITATIONS: We found important statistical heterogeneity across included studies. CONCLUSION: Considering the frequent occurrence of adverse events, prescription of thalidomide should be restricted to patients with severely refractory CLE or who are at high risk for severe scarring. PMID- 28989112 TI - A comparison of apremilast monotherapy and combination therapy for plaque psoriasis in clinical practice: A Canadian multicenter retrospective study. PMID- 28989113 TI - Utilization patterns and survival outcomes after wide local excision or Mohs micrographic surgery for Merkel cell carcinoma in the United States, 2004-2009. PMID- 28989115 TI - Osteoarthritis year in review 2017: genetics and epigenetics. AB - OBJECTIVE: The purpose of this review is to describe highlights from original research publications related to osteoarthritis (OA), epigenetics and genomics with the intention of recognising significant advances. DESIGN: To identify relevant papers a Pubmed literature search was conducted for articles published between April 2016 and April 2017 using the search terms 'osteoarthritis' together with 'genetics', 'genomics', 'epigenetics', 'microRNA', 'lncRNA', 'DNA methylation' and 'histone modification'. RESULTS: The search term OA generated almost 4000 references. Publications using the combination of descriptors OA and genetics provided the most references (82 references). However this was reduced compared to the same period in the previous year; 8.1-2.1% (expressed as a percentage of the total publications combining the terms OA and genetics). Publications combining the terms OA with genomics (29 references), epigenetics (16 references), long non-coding RNA (lncRNA) (11 references; including the identification of novel lncRNAs in OA), DNA methylation (21 references), histone modification (3 references) and microRNA (miR) (79 references) were reviewed. Potential OA therapeutics such as histone deacetylase (HDAC) inhibitors have been identified. A number of non-coding RNAs may also provide targets for future treatments. CONCLUSION: There continues to be a year on year increase in publications researching miRs in OA (expressed as a percentage of the total publications), with a doubling over the last 4 years. An overview on the last year's progress within the fields of epigenetics and genomics with respect to OA will be given. PMID- 28989114 TI - Is a randomized trial of a short course of aminoglycoside added to beta-lactam antibiotics for empirical treatment in critically ill patients with sepsis justified? PMID- 28989116 TI - Complex restitution behavior and reentry in a cardiac tissue model for neonatal mice. AB - Spatiotemporal dynamics in cardiac tissue emerging from the coupling of individual cardiomyocytes underlie the heart's normal rhythm as well as undesired and possibly life-threatening arrhythmias. While single cells and their transmembrane currents have been studied extensively, systematically investigating spatiotemporal dynamics is complicated by the nontrivial relationship between single-cell and emergent tissue properties. Mathematical models have been employed to bridge this gap and contribute to a deepened understanding of the onset, development, and termination of arrhythmias. However, no such tissue-level model currently exists for neonatal mice. Here, we build on a recent single-cell model of neonatal mouse cardiomyocytes by Wang and Sobie (Am. J. Physiol. Heart Circ. Physiol 294:H2565) to predict properties that are commonly used to gauge arrhythmogenicity of cardiac substrates. We modify the model to yield well-defined behavior for common experimental protocols and construct a spatially extended version to study emergent tissue dynamics. We find a complex action potential duration (APD) restitution behavior characterized by a nonmonotonic dependence on pacing frequency. Electrotonic coupling in tissue leads not only to changes in action potential morphology but can also induce spatially concordant and discordant alternans not observed in the single-cell model. In two-dimensional tissue, our results show that the model supports stable functional reentry, whose frequency is in good agreement with that observed in adult mice. Our results can be used to further constrain and validate the mathematical model of neonatal mouse cardiomyocytes with future experiments. PMID- 28989117 TI - Brachial artery blood flow dynamics during sinusoidal leg cycling exercise in humans. AB - To explore the control of the peripheral circulation of a nonworking upper limb during leg cycling exercise, blood flow (BF) dynamics in the brachial artery (BA) were determined using a sinusoidal work rate (WR) exercise. Ten healthy subjects performed upright leg cycling exercise at a constant WR for 30 min, followed by 16 min of sinusoidal WR consisting of 4-min periods of WR fluctuating between a minimum output of 20 W and a maximum output corresponding to ventilatory threshold (VT). Throughout the protocol, pulmonary gas exchange, heart rate (HR), mean arterial blood pressure (MAP), blood velocity (BV), and cross-sectional area of the BA, forearm skin BF (SBF), and sweating rate (SR) were measured. Each variable was fitted to a sinusoidal model with phase shift (theta) and amplitude (A). Nearly all variables closely fit a sinusoidal model. Variables relating to oxygen transport, such as VO2 and HR, followed the sinusoidal WR pattern with certain delays (theta: VO2; 51.4 +/- 4.0 degrees , HR; 41.8 +/- 5.4 degrees , mean +/- SD). Conversely, BF response in the BA was approximately in antiphase (175.1 +/- 28.9 degrees ) with a relatively large A, whereas the phase of forearm SBF was dissimilar (65.8 +/- 35.9 degrees ). Thus, the change of BF through a conduit artery to the nonworking upper limb appears to be the reverse when WR fluctuates during sinusoidal leg exercise, and it appears unlikely that this could be ascribed exclusively to altering the downstream circulation to forearm skin. PMID- 28989119 TI - Effects of protein-coated nanofibers on conformation of gingival fibroblast spheroids: potential utility for connective tissues regeneration. AB - Deep wounds in the gingiva caused by trauma or surgery require a rapid and robust healing of connective tissues. We propose utilizing gas-brushed nanofibers coated with collagen and fibrin for that purpose. Our hypotheses are that protein-coated nanofibers will: (i) attract and mobilize cells in various spatial orientations, and (ii) regulate the expression levels of specific extracellular matrix (ECM) associated proteins, determining the initial conformational nature of dense and soft connective tissues. Gingival fibroblast monolayers and 3D spheroids were cultured on ECM substrate and covered with gas-blown poly-(DL-lactide-co glycolide) (PLGA) nanofibers (uncoated/coated with collagen and fibrin). Cell attraction and rearrangement was followed by F-actin staining and confocal microscopy. Thicknesses of the cell layers, developed within the nanofibers, were quantified by imageJ software. The expression of collagen1alpha1 chain (Col1alpha1), fibronectin, and metalloproteinase 2 (MMP2) encoding genes was determined by quantitative reverse transcription analysis. Collagen- and fibrin- coated nanofibers induced cell migration toward fibers and supported cellular growth within the scaffolds. Both proteins affected the spatial rearrangement of fibroblasts by favoring packed cell clusters or intermittent cell spreading. These cell arrangements resembled the structural characteristic of dense and soft connective tissues, respectively. Within 3 days of incubation, fibroblast spheroids interacted with the fibers and grew robustly by increasing their thickness compared to monolayers. While the ECM key components, such as fibronectin and MMP2 encoding genes, were expressed in both protein groups, Col1alpha1 was predominantly expressed in bundled fibroblasts grown on collagen fibers. This enhanced expression of collagen1 is typical for dense connective tissue. Based on results of this study, our gas-blown, collagen- and fibrin coated PLGA nanofibers are viable candidates for engineering soft and dense connective tissues with the required structural characteristics and functions needed for wound healing applications. Rapid regeneration of these layers should enhance healing of open wounds in a harsh oral environment. PMID- 28989120 TI - Quality of Life Assessment should be Part of Oral Health Evaluations in Day-to day Practice. AB - According to the World Health Organization (WHO), "Health is a state of complete physical, mental, and social wellbeing and not merely the absence of disease and infirmity."1 Quality of Life (QoL) is a crucial and often required measure of an individual's general well-being. The QoL is an established term incorporating different facets of life like physical, psychological, social, economical, spiritual, cognitional, and sexual dimensions. PMID- 28989118 TI - Dual specificity phosphatase 5 and 6 are oppositely regulated in human skeletal muscle by acute exercise. AB - Physical activity promotes specific adaptations in most tissues including skeletal muscle. Acute exercise activates numerous signaling cascades including pathways involving mitogen-activated protein kinases (MAPKs) such as extracellular signal-regulated kinase (ERK)1/2, which returns to pre-exercise level after exercise. The expression of MAPK phosphatases (MKPs) in human skeletal muscle and their regulation by exercise have not been investigated before. In this study, we used mRNA sequencing to monitor regulation of MKPs in human skeletal muscle after acute cycling. In addition, primary human myotubes were used to gain more insights into the regulation of MKPs. The two ERK1/2 specific MKPs, dual specificity phosphatase 5 (DUSP5) and DUSP6, were the most regulated MKPs in skeletal muscle after acute exercise. DUSP5 expression was ninefold higher immediately after exercise and returned to pre-exercise level within 2 h, whereas DUSP6 expression was reduced by 43% just after exercise and remained below pre-exercise level after 2 h recovery. Cultured myotubes express both MKPs, and incubation with dexamethasone (Dex) mimicked the in vivo expression pattern of DUSP5 and DUSP6 caused by exercise. Using a MAPK kinase inhibitor, we showed that stimulation of ERK1/2 activity by Dex was required for induction of DUSP5 However, maintaining basal ERK1/2 activity was required for basal DUSP6 expression suggesting that the effect of Dex on DUSP6 might involve an ERK1/2-independent mechanism. We conclude that the altered expression of DUSP5 and DUSP6 in skeletal muscle after acute endurance exercise might affect ERK1/2 signaling of importance for adaptations in skeletal muscle during exercise. PMID- 28989121 TI - Protective Effect of Adhesive Systems associated with Neodymium-doped Yttrium Aluminum Garnet Laser on Enamel Erosive/Abrasive Wear. AB - AIM: This study evaluated the efficacy of self-etching adhesive systems associated or not associated with the neodymium-doped yttrium aluminum garnet (Nd:YAG) laser on the protection against enamel erosive/abrasive wear. MATERIALS AND METHODS: Bovine enamel specimens were demineralized with 0.3% citric acid (5 minutes). The samples were randomly assigned to eight groups (n = 20): SB - Single Bond Universal (3M/ESPE); SB+L - Single Bond Universal + laser (80 mJ/10 Hz); FB - Futurabond U (Voco); FB+L -Futurabond U + laser; GEN - G-aenial bond (GC); GEN+L -G-aenial bond + laser; L - laser irradiation; and C - no treatment. The laser was applied before light curing. The samples were subjected to erosive/abrasive challenges (0.3% citric acid - 2 minutes and tooth brushing four times daily for 5 days). Enamel surface loss was recovered profilometrically by comparison of baseline and final profiles. The adhesive layer thickness, retention percentage of the protective layer, and microhardness of cured adhesive were measured. Data were analyzed using one-way analysis of variance and Tukey's test (5%). RESULTS: There were significant differences for all parameters (p = 0.0001). Mean values +/- SD and results of the Tukey's test were: Surface wear: GEN - 4.88 (+/-1.09)a, L - 5.04 +/- 0.99)a, FB - 5.32 (+/-0.93)ab, GEN + L - 5.46 (+/-1.27)abc, SB + L - 5.78 (+/-1.12)abc, FB + L - 6.23 (+/-1.25)bc, SB - 6.35 (+/-1.11)c, and C - 6.46 (+/-0.61)c; layer thickness: GEN - 15.2 (+/-8.63)c, FB - 5.06 (+/-1.96)a, GEN + L - 13.96 (+/-7.07)bc, SB + L - 4.24 (+/-2.68)a, FB + L - 9.03 (+/-13.02)abc, and SB - 7.49 (+/-2.80)ab; retention: GEN - 68.89 (+/ 20.62)c, FB - 54.53 (+/-24.80)abc, GEN + L - 59.90 (+/-19.79)abc, SB + L - 63.37 (+/-19.30)bc, FB + L - 42.23 (+/-17.68) a, and SB - 47.78 (+/-18.29)ab; microhardness: GEN - 9.27 (+/-1.75)c; FB - 6.99 (+/-0.89)b; GEN + L - 6.22 (+/ 0.87)ab; SB + L - 15.48 (+/-2.51)d; FB + L - 10.67 (+/-1.58)c; SB - 5.00 (+/ 1.60)a. CONCLUSION: The application of Futurabond U and G-aenial bond on enamel surface, as well as the Nd:YAG laser irradiation alone, was able to reduce the enamel wear. The use of laser after the adhesive systems did not improve their efficacy. CLINICAL SIGNIFICANCE: Erosive/abrasive wear is a prevalent condition in clinical practice affecting many patients. The association of adhesive systems and Nd:YAG laser is of considerable clinical interest because it assesses new treatments to reduce the erosive/abrasive wear that would help dentists in clinical treatment decisions to reduce enamel wear and achieve a successful treatment. PMID- 28989122 TI - Comparison of Microleakage of Class V Cavities restored with the Embrace WetBond Class V Composite Resin and Conventional Opallis Composite Resin. AB - PURPOSE: This study was undertaken to compare the micro-leakage of class V cavities restored with the newly introduced Embrace WetBond class V (EWC) composite resin and conventional Opallis composite resin. MATERIALS AND METHODS: In this in vitro study, class V cavities were prepared on 30 extracted bovine incisors, with the gingival floor and the coronal margin of the cavities 1 mm apical and coronal to the cementoenamel junction (CEJ) respectively. The cavities measured 3 mm in length, 2 mm in width, and 1.5 mm in depth. The teeth were randomly divided into two groups. In group I, the cavities were restored with Opallis composite resin in association with ExciTE adhesive system (total-etch); in group II, the EWC composite resin was used for restorations. After 500 thermocycling procedures, the teeth were immersed in 0.5% fuchsin solution for 24 hours. Then, the samples were placed within a polyester model and sectioned in the buccolingual direction. The samples were evaluated under a stereomicroscope at *30 for the penetration of dye. The enamel and dentin margins were evaluated separately. To test ordinal results, we used nonparametric statistical methods. To find out whether each independent composite groups I and II came from the same populations, we used Mann-Whitney U test and to compare two related samples' coronal margin and gingival margin, Wilcoxon signed-rank test was used. RESULTS: There was significantly more microleakage in group II at both the enamel and dentin margins (coronal margin: p = 0.04; gingival margin: p = 0.21). In both groups, microleakage at gingival margins was significantly higher than that at coronal margins (group I: p = 0.008; group II: p = 0.26). CONCLUSION: Despite the high speed and the short process of restoration with Embrace WetBond, it is not a reliable restorative material for class V cavities due to its inadequate marginal seal. PMID- 28989123 TI - Effect of Two-minute Application of 35% Sodium Ascorbate on Composite Bond Strength following Bleaching. AB - AIM: The aim of this study is to assess the effect of 35% sodium ascorbate on microtensile bond strength of dentin immediately after bleaching with 35% hydrogen peroxide. MATERIALS AND METHODS: A total of 25 sound human 3rd molars were collected. Teeth were randomly divided into five groups for different treatments: Group I [bleaching + immediate bonding (i.e., restoration)], group II (bleaching + delayed bonding), group III (bleaching + sodium ascorbate + immediate bonding), group IV (bleaching + sodium ascorbate + delayed bonding), and group V (bonding only). After bleaching, but before bonding, groups II and IV were stored for 1 week in deionized water at 37 degrees C. All samples were bonded using OptiBoned FL (Kerr) and Filtek Supreme (3M/ESPE). Teeth were sectioned into 1 * 1 mm 2 bars, and microtensile bond strength was tested with a universal testing machine (Instron 8841) at a cross-head speed of 0.5 mm/minute. RESULTS: Microtensile bond strength differed significantly across the five groups, with a significant reduction in microtensile bond strength observed for samples in group I relative to samples in any of the other treatment groups (p < 0.05). CONCLUSION: The application of a high concentration of sodium ascorbate for a shorter time reversed the negative effect of 35% hydrogen peroxide bleaching on composite bonding strength to dentin. CLINICAL SIGNIFICANCE: The negative effects of bleaching on composite bonding can be neutralized by the application of the reversing agent sodium ascorbate thus, increasing the efficiency of clinic chair time. This is clinically relevant for those patients requiring restorative treatment immediately after in-office bleaching. PMID- 28989124 TI - Comparison of Shear Bond Strengths of Conventional Resin Cement and Self-adhesive Resin Cement bonded to Lithium Disilicate: An in vitro Study. AB - AIM: The aim of this study is to compare the shear bond strengths of conventional resin cement and self-adhesive resin cement bonded to lithium disilicate. MATERIALS AND METHODS: A total of 40 extracted human molar teeth were mounted in self-cure acrylic resin. Teeth were prepared to obtain flat occlusal surface. About 40 lithium disilicate specimens of dimension-10 mm in diameter and thickness of 2 mm-were fabricated using lost wax technique. The samples were divided into four groups: Groups I, II, III, and IV (n = 10). The specimens were surface treated with Monobond S silane coupling agent. Self-etching primer and bonding agent were applied on the bonding surface of the teeth in groups I and III. The specimens were bonded to the primed teeth with the Multilink N resin cement and subjected to the universal testing machine. The specimens were light cured. Specimens in groups II and IV were luted to teeth using self-adhesive cement RelyX U100. The same force was applied over the specimen as mentioned above. Excess cement was removed, and light curing was done. The specimens in groups III and IV were subjected to thermocycling for 10,000 cycles at temperatures altering between 5 degrees C and 55 degrees C. RESULTS: The shear bond strengths of conventional resin cement and self-adhesive resin cement with lithium disilicate were tested before and after thermocycling. Results indicated that thermocycling has no significant effect on the bond strengths of conventional or self-adhesive resin cement. However, from the study, it is seen that conventional resin cement had a higher shear bond strength value than the self-adhesive resin cement. CONCLUSION: There was a significant difference between the average shear bond strength values of conventional resin cement (Multilink N) and self-adhesive resin cement (RelyX U100) when bonded to lithium disilicate disks, and thermocycling had no significant effect on the bond strength of conventional or self-adhesive resin cements. CLINICAL SIGNIFICANCE: Among all-ceramic systems available, lithium disilicate materials have emerged as an excellent esthetic material for fabrication of anterior and posterior crowns and three-unit anterior fixed partial dentures because of their high translucency and improved optical properties. For successful clinical outcomes, the luting agent should have high bond strength not only to the ceramic surface, but also to the tooth surface. PMID- 28989125 TI - Evaluation of Antibacterial Effect and Dimensional Stability of Self-disinfecting Irreversible Hydrocolloid: An in vitro Study. AB - AIM: This study evaluated the antibacterial activity and dimensional stability of irreversible hydrocolloids mixed with different concentrations of chlorhexidine gluconate instead of water. MATERIALS AND METHODS: Experimental specimens (45 specimens) were prepared and allocated into three groups of 15 each. Group I: Impression material mixed with distilled water served as control. Groups II and III were prepared with 0.12 and 0.2% chlorhexidine gluconate solution, respectively. Specimens in each group were subjected to tests for dimensional stability. For antimicrobial activity, 30 specimens were prepared and allocated into three groups of 10 each named as group I (control), group II (0.12% chlorhexidine gluconate), and group III (0.2% chlorhexidine gluconate) similar to specimens for dimensional stability. Statistical analysis was performed using a one-way analysis of variance (ANOVA) and Tukey test. RESULTS: Zones of inhibition were observed around test specimens, but not around control specimens; there was a significant intergroup difference in the diameters of the inhibition zones. In the test for dimensional stability, no significant differences were detected among groups, and the accuracy was clinically acceptable. CONCLUSION: Irreversible hydrocolloid impression material mixed with chlorhexidine exhibits varying degrees of antibacterial activity without influencing the dimensional stability of set material. CLINICAL SIGNIFICANCE: Many contagious diseases can be prevented by practical control of infection in the dental office. Chlorhexidine gluconate, as a mixing liquid, ensures disinfection of impression, and this method of disinfection is more convenient and avoids extra effort as in other disinfection techniques. PMID- 28989126 TI - Risk Factors and Treatment Needs among Orphan School Children. AB - AIM: The aim of the study was to identify risk factors and treatment needs of orphan children of Selangor, Kuala Lumpur, Malaysia. Ob ectives: (1) To identify the association between the frequency of snacking and caries among orphan schoolchildren, (2) To assess Streptococcus mutans and Lactobacilli (microbiological assessment) in saliva of orphan children, and (3) To formulate treatment needs for orphan children. MATERIALS AND METHODS: A cross-sectional study was done among 253 children of 5-, 12-, and 15-year-olds living in various orphanage houses of Selangor, Kuala Lumpur, Malaysia. Demographic data, and dietary and oral hygiene practices were collected through a structured questionnaire. Clinical examinations of children were conducted to assess oral health status and recorded in the World Health Organization oral health assessment form (1997). Stimulated saliva was collected for S. mutans and Lactobacilli levels. The statistical software, namely, Statistical Package for the Social Sciences version 19.0 was used for the analysis of the data. RESULTS: The final data analysis included 253 children of which 116 (45.8%) were boys and 137 (54.2%) were girls. Overall, 140 (55.33%) children were caries-free and 113 (44.66%) children presented with caries (decayed/missing/filled surface >0). High levels of salivary microbiological counts (S. mutans and Lactobacilli), i.e., >=105, stress the importance of necessary preventive oral health services. Treatment needs among orphan children showed that most of the children, i.e., 58 (22.9%), need preventive or caries-arresting care followed by 49 (19.4%) who require two-surface filling as an immediate measure. CONCLUSION: From the results of our study, orphan children have low utilization of preventive and therapeutic oral health services. Urgent attention is required to plan a comprehensive dental health-care program to improve their oral health status. CLINICAL SIGNIFICANCE: Parents are the primary caretakers of children, but woefully some of them have to lead their lives without parents, the latter either being dead or incapable of bringing up their children. Such a group of children is known as orphans. As oral health is an integral part of general health, it is essential for health-care policy makers to address oral health needs of this underprivileged group of society. This article highlights the risk factors and treatment needs among orphan schoolchildren. PMID- 28989127 TI - Relationship of Body Mass Index with Diet, Physical Activities, and Lifestyles of Dental Students. AB - INTRODUCTION: The objective of the study was to investigate the prevalence of overweight issues and obesity by recording the body mass index (BMI) and explore the dietary habits, physical activities (PAs), and lifestyles of male students at the College of Dentistry, King Saud University. MATERIALS AND METHODS: A custom designed self-administrative form and questionnaire were used in this study for data collection. The first part of the form was used to record the participants' height and weight for the BMI. The participants were grouped as underweight (BMI < 18.5), normal weight (BMI = 18.5-24.9), overweight (BMI = 25-29.9), and obese (BMI > 30.0). The second part comprised questions related to the dietary habits, PAs, and lifestyles of the male dental students. Chi-squared test was used to generate the significance of each question at significance <0.05. RESULTS: A total of 211 male students (mean age 22.31 +/- 2.10 years) participated in the study (response rate 78.1%). The findings revealed that 29 and 28% of the dental students were overweight and obese respectively. A statistically significant difference (p < 0.05) between the groups was found for the questions asked about time spent exercising per day (p = 0.003), time spent sporting per week (p = 0.003), and time spent watching television and internet surfing per day (p = 0.012). CONCLUSION: The prevalence of overweight issues and obesity is high among the dental students compared with the general population of Saudi Arabia, and there is a need for intervention programs to combat obesity among the dental students. The awareness about PA, healthy diet/lifestyle, consequences of overweight and obesity on their health and profession must be increased among the dental students to avoid future complications. CLINICAL SIGNIFICANCE: The impact of obesity on individuals' oral health and its influence on dental treatment protocols and postoperative procedures has been well documented. Dental students are more prone to obesity due to their lifestyle with less PA and disordered eating habits and, thereby, are prone to obesity-related health hazards. PMID- 28989128 TI - Mechanical and Physical Properties of Two Different Resin-based Materials: A Comparative Study. AB - AIM: The purpose of this study was to evaluate the degree of conversion (DC) of two different resin-based composite materials (nanofill composite and ormocer) and correlate it with some mechanical properties of these two restorative materials. MATERIALS AND METHODS: Two different resin-based materials (Filtek Supreme XT and Admira) were tested. A total of 30 samples of each type of selected composite were prepared. Specimens were immersed in distilled water for 24 hours. Then, the specimens were subjected to DC, hardness, and diametral tensile strength (DTS) measurements. The data obtained were tabulated for statistical analysis. The t-test was used to detect the significant difference among the variables tested in this study. Furthermore, the interrelationship between the studied parameters was investigated using a simple correlation coefficient statistical test. RESULTS: Statistically significant differences were observed regarding DC, hardness, and DTS. Filtek Supreme XT presented the highest values. There was a positive correlation between DC and hardness. Also there was a correlation between DC and DTS, but it was not significant. CONCLUSION: Under the tested experimental conditions, the DC of Filtek Supreme XT was higher than that of ormocer. Accordingly, Filtek Supreme XT showed better mechanical properties. CLINICAL SIGNIFICANCE: Filtek Supreme XT showed superior mechanical properties. Therefore, orthodontic bracket-based composite combinations may also be expected to perform well clinically over the lifetime of a bonded orthodontic appliance. PMID- 28989129 TI - Assessment of Influence of Contact Time between Alginate and Type III Dental Stone on Properties of Cast Model: An in vitro Study. AB - INTRODUCTION: Alginate is a versatile, irreversible hydrocolloid impression material, which is cost-effective and forms an essential component in dental practice. For elevating the hardness of the cast models, hardeners are combined with stone. Hence, we planned the present study to evaluate the impact of altering the time of contact between alginate and stone after various interim periods. MATERIALS AND METHODS: The present study included the assessment of impact of time of contact between alginate and stone by the construction of 90 casts using a cylinder model. Two bisecting lines were marked and were named as y and y'. These lines were used for testing the dimensional stability. Using chemically cured acrylic resin, the construction of ten special trays was done. All the impression casts were randomly divided into two study groups, with 45 casts in each group-group I: control group, casts were removed after 60 minutes; group II: study group, casts were removed after 9 hours. A digital caliper was used for measuring the dimensional stability of the cast. All the data were collected and analyzed. RESULTS: In the specimens of the control group (group I) and the study group (group II), the mean dimensions from y to y' were found to be 17.54 and 17.95 respectively. The mean reading of hardness in the control group and study group was found to be 0.59 and 0.20 respectively. In groups I and II, the number of specimens showing clarity of two lines (X and X") was 0 and 5 respectively. CONCLUSION: There was no change in the dimensional stability of the dental stone model when the contact time was increased. CLINICAL SIGNIFICANCE: Within certain limits, the contact time between alginate and stone can be altered without significantly altering the properties of the cast. PMID- 28989130 TI - Evaluation of the Sealing Capability of the Internal Conical Connections of Implants with Titanium and Zirconia Abutments. AB - AIM: The purpose of this in vitro investigation was to evaluate the sealing capability of the conical implant-abutment interfaces under different abutment screw torque values using titanium and zirconia abutments with Morse taper designs. MATERIALS AND METHODS: A total of 42 dental implants (n = 21 for titanium abutments and n = 21 for zirconia abutments) were inoculated internally with three bacteria. These assemblies were divided into four test groups (n = 10) based on screw fixation torques of 35 or 20 Ncm and placed in sterile broth; the remaining abutments were used as positive controls and torqued to 10 Ncm. Microleakage was quantified by enumerating the bacteria from the colony-forming units. An analysis of variance for the estimates of bacteria enumerated and microgaps was used with a post hoc analysis as indicated. A p-value of 0.05 was used as the level of significance. RESULTS: There was no statistically significant difference in microleakage among the four test groups; there were no significant effects of screw torque or abutment type on the bacteria enumerated. There was a significantly smaller mean microgap with the zirconia abutments. CONCLUSION: The results of this study indicated no statistically significant difference in the sealing capabilities between titanium and zirconia abutments, having internal conical connections, after increasing the abutment screw torque. CLINICAL SIGNIFICANCE: It is important for clinicians to follow the guidelines suggested by the implant companies to avoid biomechanical complications over time. PMID- 28989131 TI - Comparison of Hypersensitivity in Metal Ceramic Crowns cemented with Zinc Phosphate and Self-adhesive Resin: A Prospective Study. AB - BACKGROUND: Luting agents used to fix artificial prostheses, such as fixed partial denture (FPD) to tooth are basically viscous in nature and show chemical reaction for fixation. Postcementation hypersensitivity is a frequent complaint of patients. The present study was conducted to compare postcementation hypersensitivity with zinc phosphate and self-adhesive resin in complete coverage crown. MATERIALS AND METHODS: This study included 30 patients in which 60 porcelein fused to metal crowns was placed. Two metal crowns were placed in each patient in nonantagonis-tic contralateral quadrants. First crown was cemented with zinc phosphate cement, while the other was cemented with self-adhesive resin. Hypersensitivity was evaluated by visual analog scale (VAS) score and by clinical test. For clinical evaluation of sensitivity, hot and cold water was applied to the cervical margin of restoration for 5 seconds and response was recorded. RESULTS: This study consisted of 30 patients in which 60 crowns were given. There was no statistical difference in VAS score of mastication in zinc phosphate cement recorded at baseline, 1 week, 4 weeks, 6 months, 1 year, and 2 years (p > 0.05). Cold response also did not show a significant difference at six time points. Warm response showed slight decrease in subsequent time points but was nonsignificant (p > 0.05). Similarly, with self-adhesive resin cement, VAS score during mastication, hot and cold response was statistically nonsignificant (p > 0.05). CONCLUSION: Postcementation hypersensitivity is a frequent complaint that patient may experience. However, we found no statistically significant difference in both cements tested. CLINICAL SIGNIFICANCE: Postcementation hypersensitivity is an unpleasant sensation experienced by patients. This may affect the success of any prosthesis. Thus, selection of luting agent for cementation plays an important role to eliminate this symptom. PMID- 28989132 TI - Post-insertion Posterior Single-implant Occlusion Changes at Different Intervals: A T-Scan Computerized Occlusal Analysis. AB - AIM: The aim of this prospective cohort study was to evaluate the postinsertion posterior single-implant occlusion changes at 3- and 6-month intervals using T Scan computerized occlusal analysis. MATERIALS AND METHODS: A total of 21 patients received single implant, opposed by natural dentition, in posterior regions of the maxilla or mandible (13 premolar, 8 molar) and were finally restored with cemented-retained metal-ceramic crowns. The occlusal contacts were equilibrated according to the implant-protective occlusion concept to develop light contact with heavy occlusion and no contact with light occlusion in maximum inter-cuspation. The percentage of force applied to the implant crowns (POFI) and contralateral teeth (POFT) was evaluated using T-Scan computerized occlusal analysis at prosthesis insertion, 3- and 6-month follow-up appointments. The data were statistically analyzed using Friedman test and Wilcoxon post hoc test (alpha = 0.05). RESULTS: The POFI values at the 6- and 3-month follow-up appointments were significantly higher than those at prostheses insertion (p = 0.001 and p = 0.005 respectively). In addition, there were significant differences between the POFI at 3- and 6-month follow-up (p = 0.020). However, the POFT values at 3- and 6-month follow-up appointments were significantly lower than those at baseline (p < 0.001). CONCLUSION: The intensity of occlusal contacts of implant-supported prostheses opposed by natural dentition gradually increased after prosthesis insertion. Placement of single posterior implant-supported restoration decreased the percentage of occlusal force applied to contralateral arch. CLINICAL SIGNIFICANCE: A periodic occlusal adjustment of implant-supported prostheses is necessary to prevent potential overloading from the movement of opposing natural dentition. PMID- 28989133 TI - Gingival Crevicular Fluid Turnover Markers in Premenopausal vs Postmenopausal Women receiving Orthodontic Treatment. AB - BACKGROUND: Orthodontic treatment is one of the commonly used dental treatments. Orthodontic forces act on the bone by modulating the biomolecules, chiefly the osteoprotegerin (OPG), osteopontin (OPN), receptor activator of nuclear factor kappa-B (RANK), and RANK ligand (RANKL) (OPG ligand). Hormonal changes are known to cause marked alteration in the levels of these biomolecules. Hence, we planned this study to evaluate the response of bone biomarkers in the gingival crevicular fluid (GCF) in postmenopausal women undergoing fixed orthodontic therapy. MATERIALS AND METHODS: This study included assessment of 50 subjects who underwent orthodontic treatment from June 2012 to July 2016. All the patients were divided into two study groups with 25 patients in each group: premenopausal group and postmenopausal group. Similar orthodontic wires were used for controlling the forces applied in subjects of both the study groups and their GCF levels of RANKL, and OPN was assessed at baseline and 24 hours after the activation of orthodontic forces. All the results were compiled, assessed, and analyzed by Statistical Package for the Social Sciences software version 16.0. Chi-square test, Student's t-test, and Mann-Whitney U test were used for the assessment of the level of significance. RESULTS: The mean values of RANKL and OPN in the premenopausal and postmenopausal groups were found to be 241.52 and 317.15 pg/MUL respectively. The mean values of RANKL at baseline in the premenopausal and postmenopausal groups were found to be 7.15 and 3.84 pg/MUL respectively. Nonsignificant results were obtained while comparing mean OPN and RANKL level alteration in between the two study groups. CONCLUSION: The mean alterations in the GCF levels of bone biomarkers are similar for both premenopausal and postmeno-pausal women. CLINICAL SIGNIFICANCE: For women with either premenopausal or postmenopausal status, orthodontic treatment appears to be equally safer. PMID- 28989134 TI - Influence of Energy Beverages on the Surface Texture of Glass lonomer Restorative Materials. AB - BACKGROUND AND OBJECTIVE: The objective of the study was to find whether energy beverages have an erosive effect, leading to a risk in the clinical performance of glass ionomer restorative materials. AIM: This study evaluated the influence of energy beverages on the surface texture of glass ionomer restorative materials. MATERIALS AND METHODS: Glass ionomer materials used were Ionofil Plus AC, GC EQUIA, and Ketac Molar; energy beverages are Code Red, Red Bull, and Power Horse. Specimens prepared were discs of 8 mm diameter and 3 mm thickness; specimens from each material were evaluated following aging with Code Red, Red Bull, and Power Horse energy beverages. Distilled water was used as a control. The surface roughness (Ra) was assessed by surface scanning interferometry. The surface roughness values (DeltaRa and Ra) were measured for each specimen. The data were analyzed statistically using multiple repeated measures [analysis of variance (ANOVA)] and paired data t-test (p < 0.05 was considered as the significance level). RESULTS: The surface roughness (DeltaRa and Ra) values before and after aging using Code Red, Red Bull, and Power Horse energy beverages differ significantly for all the materials regardless of the immersion time (p < 0.05). All the materials showed roughness changes after immersion periods of 1 day, 1 week, and 1 month. CONCLUSION: It can be concluded that all energy beverage solutions used in this study had an adverse effect on the surface roughness degradation of the tested glass ionomers with increasing immersion time. CLINICAL SIGNIFICANCE: Energy beverages have an erosive effect on glass ionomer, which influences the clinical importance of the material; it also has anticarious property because it releases the fluoride. PMID- 28989135 TI - Study to assess Activity and Concentration of Gammaglutamyl Transpeptidase in Precancerous and Cancer Patients and Its Comparison with Controls. AB - OBJECTIVE: The purpose of the study is to highlight the use of gamma-glutamyl transpeptidase (GGT) as salivary enzyme tumor marker and assess the activity and concentration of GGT in precancerous and cancer patients and compare it with the normal control. MATERIALS AND METHODS: Individuals in the age group of above 20 years were included in the study. In this study, salivary GGT was analyzed in 75 cases. The selected patients were divided into three main groups as group I (controls with normal health), group II (patients with precancerous lesions and conditions), and group III (patients with oral cancer lesions). All the selected individuals were analyzed for salivary GGT. RESULTS: A significant difference was observed between control and precancerous groups with GGT values at 5% level of significance. The mean GGT value is significantly higher in precancerous group as compared with control group (p < 0.05). A significant difference was observed between control and cancerous groups with GGT values at 5% level of significance. The mean GGT value is significantly higher in cancerous group as compared with control group (p < 0.05). A significant difference was observed between precancerous and cancerous groups with GGT values at 5% level of significance. The mean GGT value is significantly higher in cancerous group as compared with precancerous group (p < 0.05). CONCLUSION: There is a remarkable increase in salivary GGT activity in both precancerous and cancerous conditions. The increased activity was more marked in cancerous conditions than in precancerous conditions. The GGT levels were two- to threefold increased in precancerous conditions as compared with control group. This finding was statistically significant and also suggested the strong correlation between GGT levels and presence of precancerous conditions. CLINICAL SIGNIFICANCE: Integration of all these observation strengthens our thinking that elevation of salivary GTT in pre cancerous and cancerous conditions can be a reliable biomarker in early detection and prevention of oral malignancy. PMID- 28989136 TI - Morphology of the Dentin-resin Interface yielded by Two-step Etch-and-rinse Adhesives with Different Solvents. AB - AIM: The study aimed to analyze the morphology of the dentin-resin interface yielded by two-step etch-and-rinse adhesive systems with different solvents and compositions. MATERIALS AND METHODS: A total of 32 dentine disks were prepared and randomly assigned to four groups of one-bottle etch-and-rinse adhesive systems containing different solvents: group I, Adper Scotchbond-IXTTM (ethanol/water); group II, XP-BondTM (tertiary butanol); group III, Prime and Bond NT(r) (acetone); and group IV, One Coat bond(r) (5% water). Adhesive systems were applied onto dentin disks, which were then thermal cycled, divided into two hemi-disks (n = 16), and prepared for field-emission scanning electron microscopy to examine the dentin-resin interdiffusion zone. Microphotographs were scanned and data were processed. Data were compared with analysis of variance multivariant test after Kolmogorov-Smirnov and Shapiro-Wilk tests using Statistic Package for the Social Sciences. RESULTS: The adhesive layer thickness average found was group I: 45.9 +/- 13.41 urn, group II: 20.6 +/- 16.32 urn, group III: 17.7 +/- 11.75 urn, and group IV: 50.7 +/- 27.81 urn. Significant differences were found between groups I and IV and groups II and III (p < 0.000). Groups I (3.23 +/- 0.53 MUm) and II (3.13 +/- 0.73 MUm) yielded significantly thicker hybrid layers than groups III (2.53 +/- 0.50 MUm) and IV (1.84 +/- 0.27 MUm) (p < 0.003). Group III presented a less homogeneous hybrid layer, with some gaps. Tag length average was greater in groups II (111.0 +/- 36.92 MUm) and IV (128.9 +/- 78.38 MUm) than in groups I (61.5 +/- 18.10 MUm) and III (68.6 +/- 15.84 MUm) (p < 0.008). CONCLUSION: Adhesives systems with different solvents led to significant differences in the dentin-resin interface morphology. Solvents role in adhesives bond strength should be considered together with the other adhesive system components. CLINICAL SIGNIFICANCE: The adhesive containing tertiary butanol, in addition, seems to originate a good-quality hybrid layer and long, entangled tags and also appears to have greater ability to originate microtags, which may indicate higher bond strength. PMID- 28989137 TI - Characteristic of Malocclusion among Saudi Special Need Group Children. AB - INTRODUCTION: The present study analyzed the characteristics of malocclusions, occlusal traits among Special Health care Needs (SHCN) children with Down syndrome (DS) and autism disorder (AD) in Riyadh City, Kingdom of Saudi Arabia. MATERIALS AND METHODS: A total of 100 DS and 100 AD children from five rehabilitation centers in and around Riyadh, Kingdom of Saudi Arabia, were included in the study. Any children with history of ongoing medical treatment, extraction, or orthodontic treatment were excluded from the study. Out of the 200 patients examined, 131 were males and 69 were females and the age of the children ranged from 6 to 14 years. The children were examined for malocclusion characteristics using the Angle's classification of malocclusion, and also other occlusal traits, such as overjet, overbite, cross bite, and open bite were also determined. The data obtained were analyzed using Statistical Package for the Social Sciences, version 16 to generate descriptive statistics for each variable. RESULTS: The analyzed data of the right and left permanent molar relation showed higher incidence of class III malocclusion (66%) in DS children as compared with (3-4%) AD children. The AD children presented with higher percentage of class I malocclu-sion (40-41%) as compared with (10-14%) DS children. During examination of the primary molars, the analyzed data showed that left primary molar had more mesial shift in AD children as compared with DS children. CONCLUSION: Down syndrome children had high incidence of class III malocclusion and autistic children had high incidence of class I malocclusion. Overall, the DS children were more prone to malocclusion. CLINICAL SIGNIFICANCE: This study provides database for health professionals in Saudi Arabia in regard to malocclusion of autis-tics and DS patients. PMID- 28989138 TI - Knowledge, Attitude, and Practices regarding Pharmacovigilance and Adverse Drug Reaction reporting among Dental Students in a Teaching Hospital, Jodhpur, India: A Cross-sectional Study. AB - INTRODUCTION: This is a cross-sectional knowledge, attitude, and practices (KAPs) study on pharmacovigilance (PV) and adverse drug reaction (ADR) reporting among dental students in a teaching hospital in India. AIM: The aim of this study was to assess the KAP of dental students regarding PV, ADR reporting, and barriers toward the same. MATERIALS AND METHODS: A cross-sectional survey using a self administered, investigator-developed, close-ended questionnaire was conducted in an academic dental hospital in India. All prescribers including third year students, final year students, and house surgeons of the same institute were included for assessment of KAP regarding PV using 16, 8, and 8 items respectively. Data regarding barriers toward ADR reporting and demographics were also collected. Mann-Whitney U-test and Kruskal-Wallis test were applied followed by post hoc test. RESULTS: A total of 241 of 275 respondents participated in the study with a response rate of 87.5%. Overall, 64% reported that they had no idea about the term PV. Age was significantly associated with knowledge (p = 0.045) and attitude (p = 0.016). Barriers contributing to underreporting were difficulty in deciding whether or not an ADR has occurred (52.0%), concerns that the report may be wrong (37%), lack of confidence to discuss ADR with colleagues (29%), and almost no financial benefits (24%). CONCLUSION: Participants had a comparatively favorable attitude toward PV, but their knowledge and practice need considerable improvements. This study highlights the need for appropriate dental curriculum changes and further multicentric studies to shed more light on important issues of PV among dentists in India. CLINICAL SIGNIFICANCE: This study explores dentists' knowledge, attitude, and behavior regarding PV, which could help to improve patient's safety and care. The favorable attitude of dentists is an indication that PV could be added in depth in the curriculum and in general practice. Information on barriers for reporting the ADRs could help to find possible solutions for removing the barriers precisely. PMID- 28989139 TI - Prevalence of Periodontal Destruction and Putative Periodontal Pathogens in the Same Lebanese Family. AB - AIM: Periodontal diseases are associated with microorganisms rich in Gram negative species. Several studies have indicated the presence of few a periodontopathic microorganisms in the same family. A parent with severe adult periodontitis, who is infected with bacteria associated with periodontal disease, may function as a source of infection. Their children may be at a greater risk to become colonized with bacteria. The purpose of this investigation was (1) to explore the presence of three bacteria, such as Porphyromonas gingivalis (PG), Prevotella intermedia (PI), and Aggregatibacter actinomycetemcomitans (AA) in the same Lebanese family and (2) to study the clinical destruction in the same family and their relations as members of this family due to the presence of PG. MATERIALS AND METHODS: A total of 10 families were screened; only 5 (13 females and 5 males) were selected for this study, and at least one member of the family had untreated periodontal disease, chronic or aggressive. Every participant signed an informed consent form. A total of 18 available deoxyribonucleic acid (DNA) samples were taken to analyze the presence of three periodontal bacteria. STATISTICS: Multiple logistic regression was used for the exact methods. RESULTS: All 18 patients showed a positive result for PI. Also, PG. was recognized in 15 patients while AA was not detected in any of the subjects. All couples suffered from periodontitis, chronic or aggressive forms, five children suffered from gingivitis, three children had no clinical manifestation, and only one suffered from localized aggressive periodontitis. The statistical analysis showed with each 1 year of increase in age, the odds of having periodontal disease multiply by 1.39, i.e., age as a risk factor for periodontal disease due to the presence of PG and sharing the same plate. CONCLUSION: This investigation demonstrates a high prevalence of periodontal microorganisms in children and young adults of Lebanese periodontitis parents and a microbiological similarity between the children and their mothers. All these factors could be a high risk of developing periodontal disease in the future. CLINICAL SIGNIFICANCE: This article shows that vertical transmission of microorganisms is a possible risk factor for developing periodontal disease in the offspring. PMID- 28989140 TI - Comparative Evaluation of Myeloperoxidase Enzymatic Activity in Gingival Crevicular Fluid of Subjects having Orthodontic Treatment by Different Aligning Arch Wires. AB - INTRODUCTION: There exist a number of factors that affect the outcome of orthodontic treatment. These factors can be assessed by various gingival markers. One such maker is myeloperoxidase (MPO). Hence, we planned the present study to assess and compare the MPO activity in the gingival crevicular fluid (GCF) of subjects undergoing orthodontic treatment by different aligning arch wires. MATERIALS AND METHODS: The present study included assessment of patients who underwent orthodontic treatment for crowding of anterior teeth. Diagnostic cast models of all the subjects were made for recording the irregularity index. All the subjects were randomly divided into three study groups with 15 patients in each group based on the type of nickel-titanium (NiTi) arch wires used. A collection of GCF samples was done in all the patients at various time intervals and it was sent to the laboratory for assessment of MPO activity. Activity of the MPO enzyme was expressed in terms of number of units per 100 MUL. All the results obtained were compiled and analyzed by Statistical Package for the Social Sciences (SPSS) software. RESULTS: We observed that nonsignificant results were obtained while comparing the mean age and mean gingival score in all the study groups. However, significant results were obtained on comparing the mean MPO enzymatic activity in all the study groups at different time intervals. CONCLUSION: Both superelastic NiTi and heat-activated NiTi generate optimal forces, which are necessary for higher metabolic response of the periodontal ligament. CLINICAL SIGNIFICANCE: In the intimal stages of orthodontic treatment, both superelastic NiTi and heat-activated NiTi wires are superior in leveling and aligning the crowded teeth. PMID- 28989141 TI - Melanotic Macule in Conjunction with a Giant Cell Fibroma. AB - INTRODUCTION: The aim of this study is to describe a case of a melanotic macule found in conjunction with a giant cell fibroma (GCF). For oral pigmented lesions without an identifiable etiologic factor, critical factors in determining the differential diagnosis are clinical history, symmetry, and uniformity of the lesions. Potential differential diagnosis includes racial pigmentation, endocrine disturbance, Peutz-Jeghers syndrome, trauma, hemochromatosis, oral malignant melanoma, or idiopathic etiology and melanotic macules. Melanotic macules are the most common solitary pigmented melanocytic lesions in the oral mucosa, corresponding to 86.1% of melanocytic lesions of the mouth. Giant cell fibromas are reactive connective tissue lesions in the oral cavity. They were first described as a distinct entity in 1974 by Weathers and Callihan and make up around 5 to 10% of all oral mucosa fibrous lesions. They are commonly mistaken for other growths, such as pyogenic granuloma and fibroma, and diagnosis is accurately based on its distinctive histopathology. This article presents the clinicopathologic findings of a 15-year-old Hispanic male presenting for biopsy of a melanotic macule on the mandibular anterior buccal gingiva. Histologic evaluation of the specimen revealed that the lesion also contained a GCF. Pathologic lesions of the mouth should be carefully diagnosed. Conventionally, histologic evaluation is the gold standard to produce a final diagnosis. As evidenced in this article, multiple lesions may exist in a site and may be mistakenly diagnosed as a single entity. CLINICAL SIGNIFICANCE: While each lesion has been reported individually, in reviewing the literature, no cases were reported in which both histopathologic findings of GCF and melanotic macule were present within the same lesion. PMID- 28989142 TI - [Expression and spatial distribution of P2X7 receptor in pilocarpine-induced epileptic rat hippocampus]. AB - OBJECTIVE: To investigate the dynamic expression and spatial distribution of P2X7 receptor in pilocarpine-induced epileptic rat hippocampus.? Methods: Status epilepticus (SE) model of rats was established by intraperitoneal injection with chloride lithium and pilocarpine. Rat brain tissue and hippocampus were collected at 1, 3, 7, 14, 28 days after SE. The protein expression of P2X7 receptor in rat hippocampus was detected by Western blot. The distribution of P2X7 receptor in hippocampal sub-region was analyzed by immunohistochemistry.? Results: Bilateral forelimb clonus appeared at (33.9+/-12.3) min after intraperitoneal injection with pilocarpine. The protein expression of P2X7 receptor was increased at 1d after SE, while it was decreased gradually from 3 d to minimum at 7 d, then it was elevated continuously to 28 d. Among them, the expression of P2X7 receptor was increased significantly at 1, 14 and 28 d post-SE (P<0.05). Immunohistochemical staining showed that P2X7 receptor was detected in all areas. The expression pattern of P2X7 receptor in hippocampal DG and CA3 area was consistent with protein expression, but its expression in hippocampal CA1 area was not significantly changed after SE.? Conclusion: The expression of P2X7 receptor in post-SE hippocampus is in a time-dependent manner and spatial specificity. P2X7 receptor might be involved in the development of chronic epilepsy. PMID- 28989143 TI - [Protective effect of mitochondria-targeted antioxidant SS31 on early brain injury following subarachnoid hemorrhage in rats]. AB - OBJECTIVE: To evaluate protective effects of SS31 on early brain injury (EBI) induced by subarachnoid hemorrhage (SAH) in rats.? Methods: A total of 96 Sprague Dawley rats were randomly divided into 4 groups: A sham group, an SAH group, an SAH+vehicle group (SAH+V), and an SAH+SS31 group. The SAH-induced prechiasmatic cistern rat model was established in this study. Neurological deficit scores were evaluated at 24 h after SAH. The SS31 (5 mg/kg) as well as equal volume of vehicle were administrated intraperitoneally at 2 h after SAH. The neurological scores, brain edema, blood-brain barrier (BBB) permeability, apoptosis, malondialdehyde (MDA), glutathione peroxidase (GPx) activity, superoride dismutase (SOD) activity, and the expression of cytosolic cytochrome c (Cyt C) and Bax were analyzed at 24 h after SAH.? Results: Treatment with SS31 could significantly reduce MDA levels, and restored the activities of GPx and SOD in the cortex following SAH when compared with the SAH+V group. In addition, Bax SS31 trearment increased or decreased the levels of mitochondrial Cyt C or Bax, respectively. Moreover, SS31 treatment ameliorated brain edema and Evans blue dye extravasation, improved neurological deficits, and decreased neuronal apoptosis at 24 h after SAH.? Conclusion: SS31 could alleviate EBI after SAH through its antioxidant property and ability in inhibition of neuronal apoptosis. PMID- 28989144 TI - [Role of mimecan in development of atherosclerosis induced by increased blood pressure variability]. AB - OBJECTIVE: To examine the changes of mimecan protein expression in development of atherosclerosis induced by sinoaortic denervation, and to explore the effects of mimecan knock down on the proliferation and migration of vascular smooth muscle cells.? Methods: The animals were randomly divided into a sham group and a model group (n=8 in each group). The rat model of blood pressure variability was established by sinoaortic denervation, and the hemodynamic indexes were recorded 20 weeks after the surgery to confirm the success of the model. The thoracic aorta was excised and stained with immunohistochemistry to observe the pathological changes of smooth muscle tissues and the changes of mimecan expression. The mice vascular smooth muscle cells were isolated, and which were treated with mimecan siRNA to knock down the mimecan expression. The cell proliferation was observed by 5-ethynyl-2'-deoxyuridine (Edu) in corporation test and the changes of cell migration was observed by wound healing test.? Results: Twenty weeks after sinoaortic denervation, the blood pressure variability in the model group was significantly increased compared with that in the sham group, suggesting the model was successfully established. In addition, the increased blood pressure variability in the model group promoted the proliferation and migration of the vascular smooth muscle cells in thoracic aorta, while the expression of mimecan protein was significantly decreased. In in vitro assays, the knock down of mimecan in mice vascular smooth muscle cells could promote the cell proliferation and migration.? Conclusion: Mimecan plays a protective role in the development of sinoaortic denervation induced atherosclerosis through amechanism involving suppression of the proliferation and migration of vascular smooth muscle cells. PMID- 28989145 TI - [Clinical and genetic diagnosis in a hereditary hemorrhagic telangiectasia family]. AB - OBJECTIVE: To investigate the clinical features and feasibility genetic diagnosis in a hereditary hemorrhagic telangiectasia (HHT) family, and to explore the application of gene mutation testing in HHT diagnosis.? Methods: Medical histories and clinical features of a family were analyzed to diagnose HHT patients and suspected individuals according to the clinical diagnostic criteria. Sequence analysis of endoglin (ENG) and activin A receptor like type 1 (ACVRL1) gene in the proband was performed with PCR and Sanger sequencing technology. After the possible pathogenic mutation was identified in the proband, the specific mutation was detected in the suspected individuals and part of other family members. Then the genetic diagnoses were concluded.? Results: There were 5 family members in 4 generations manifested with epistaxis. According to the clinical diagnosis criteria, the proband with epistaxis, mucocutaneous telangiectases, visceral arteriovenous malformation and family history was diagnosed as HHT; while 2 survival family members with epistaxis and family history were suspected individuals. A substitution mutation in the 5' untranslated region(5'-UTR) of ENG c.1-127 C>T was detected in the proband and the 2 suspected individuals, which did not exist in other family members. Based on the clinical and genetic findings, the 2 clinically suspected individuals were diagnosed as HHT.? Conclusion: There is great variability of the clinical manifestations among HHT patients. ENG c.1-127 C>T mutation is the possible pathogenic variant of the HHT family. A combination of clinical and genetic diagnosis could improve the diagnosis and treatment of HHT. PMID- 28989146 TI - Epicutaneous sensitization with ovalbumin, staphylococcal enterotoxin B and vitamin D analogue induces ?atopic dermatitis in mice. AB - OBJECTIVE: To illuminate a method for establishment of a cost-efficient atopic dermatitis (AD) mouse model by topical application of ovalbumin (OVA), super antigen staphylococcal enterotoxin B (SEB), and calcipotriene ointment (CO) on the back of BALB/c mice.? Methods: Experimental mice were topically treated with OVA/SEB or OVA/SEB/CO every other day during 15 days of induction. Clinical alterations on the skin area were monitored every other day. Epidermal thickness were measured by reflectance confocal microscope (RCM) before harvest. Inflammatory cells in skin biopsies were marked by hematoxylin-eosin (HE) staining. Blood sample and skin biopsies were measured by ELISA and quantitative real-time PCR to detect the expression of IL-2, IL-4, IL-31, interferon (IFN) gamma, tumor necrosis factor (TNF)-alpha pruritus-associated nerve growth factor (NGF), and serum IgE.? Results: Human AD-like cutaneous local inflammatory reaction was characterized by the accumulation of inflammatory cells, increased epidermal thickness and serum IgE levels as well as Th1 cell-associated cytokines (IFN-gamma, TNF-alpha), Th2 cell-associated cytokines (IL-4, IL-31), and NGF in the OVA/SEB/CO group compared with that in the normal control group or the OVA/SEB group.? Conclusion: OVA/SEB/CO can induce an AD-like mouse model with lower economic and time consumption. PMID- 28989147 TI - [Effect of low intensity pulsed ultrasound on expression of TGF-beta1 and Smads during dentin injury and repair]. AB - OBJECTIVE: To explore the effect of low intensity pulsed ultrasound (LIPUS) on TGF-beta1/Smad 2, 3 signal pathway during the dentin injury and repair.? Methods: Among 25 Sprague-Dawley rats, 5 rats served as a blank control group without treatment. The remaining 20 rats received modified caries preparation inbilateral maxillary first molars to establish a model of dentin-pulp injury and repair. The right maxillary first molars served as a LIPUS group, which received LIPUS irradiation (frequency: 1.5 MHz, pulse width: 200 MUs, pulse repetition frequency: 1 kHz, spatial averaged temporal averaged intensity: 30 mW/cm2, 20 min/d), and the left maxillary first molars served as a cavity-prepared group, which received fake LIPUS irradiation. The rats were sacrificed at 1, 3, 5, 7 and 14 days after LIPUS irradiation. Immunohistochemical staining and Image-pro plus 6.0 were applied to detect the expression and distribution of transforming growth factor-beta1 (TGF-beta1) and small mothers against decapentaplegic 2/3(Smad 2 and Smad 3).? Results: Immunohistochemical staining showed that the expression of TGF beta1 and Smad 2, 3 were low innormal pulp, but they were increased in different degree after dentin injury. The result of image analysis showed that the expression of TGF-beta1 in the cavity-prepared group gradually increased at the first day and peaked at day 5, and then it returned to normal level at day 14. However, the expression of TGF-beta1 in the LIPUS group were significantly higher than that in the cavity-prepared group at day 3 and 5 (both P<0.05). The expressions of Smad 2,3 in both the LIPUS group and the cavity-prepared group were consistently increased all the way, but the expressions in the LIPUS group were higher compared with that in the cavity-prepared group (P<0.05).? Conclusion: The TGF-beta1/Smad 2, 3 signal pathway can be activated during the dentin injury and repair. LIPUS can up-regulate the expression of TGF-beta1 and Smad 2, 3 in the early period, which may take part in the dentin-pulp complex injury and repair process. PMID- 28989148 TI - [Effect of growth hormone on osteopontin expression during orthodontic tooth movement in rats]. AB - OBJECTIVE: To investigate the effect of growth hormone on osteopontin expression during orthodontic tooth movement in rats.? Methods: Forty male Wistar rats (2 weeks, average weight 200 g) were randomly divided into a control group and an experimental group (n=20 per group). The experimental group received subcutaneous injections of growth hormone at a dose of 0.15 U/(kg.d), and the control group received equivalent volumes of saline. A nickel-titanium spring was fixed between the maxillary incisors and the left upper first molar with a force of 0.49 N to move the molar mesially. All rats were sacrificed on day 3, 7, 10 or 14 with cardiac perfusion. And the left side of upper jaw was removed. The longitudinal section of the first molar was prepared from sagittal direction to observe osteopontin expression in the pressure area between the mesial buccal root and distal buccal root by immunohistochemical staining and semi-quantitative analysis.? Results: The positive expression of osteopontin in the 2 groups showed similar trend, which was increased firstly and then was decreased. The expression of osteopontin on day 7 in the experimental group showed strong positive expression but it was decreased significantly on day 10 compared with the control group (P<0.05).? Conclusion: Systemic application of growth hormone could affect the expression of osteopontin and probably plays an important role in regulating bone resorption in the compression area during orthodontic tooth movement in rats. PMID- 28989149 TI - [Airborne fine particle decreases the cell viability and induces inflammation in human bronchial epithelial cells]. AB - OBJECTIVE: To investigate the effects of airborne fine particle on cell viability and inflammation in human bronchial epithelial cells.? Methods: Atmospheric PM2.5 samples were collected by PM2.5 sampler. PM2.5 morphology was observed by scanning electron microscope (SEM). Human bronchial epithelial cells (BEAS-2B) were treated with PM2.5 at different concentrations (0, 50, 100, 200, 400, 800 MUg/mL) for 12, 24 or 48 hours, and the cell activity were evaluated by cell counting kit-8 (CCK-8). The mRNA expression levels of (granulocyte-macrophage colony stimulating factor,GM-CSF) and TNF-alpha were detected by quantitative real-time PCR (qRT-PCR). Western blot was used to detect the protein expressions of GM-CSF and TNF-alpha.? Results: According to SEM, the shape of PM2.5 varied, and the diameter was different and mostly equal to or less than 2.5 MUm. CCK-8 assay showed that different concentrations of PM2.5 exposure for 12 hours, 24 hours and 48 hours resulted in loss of cell viability of BEAS-2B cells (P<0.05). Different concentrations of PM2.5 increased the mRNA and protein expression of GM CSF and TNF-alpha, and the higher concentration of PM2.5 induced higher expression, which have statistical significant difference between the groups (P<0.05).? Conclusion: Atmospheric PM2.5 can cause inflammatory response in human bronchial epithelial cells. They can reduce cell viability, which may be related to the PM2.5 trigger and aggravation of bronchopulmonary inflammatory diseases. PMID- 28989150 TI - [Parecoxib suppresses the increase of neutrophil-to-lymphocyte ratio after the modified radical mastectomy]. AB - OBJECTIVE: To observe the effect of parecoxib on neutrophil-to-lymphocyte ratio (NLR)after the modified radical mastectomy, and to explore its potential mechanisms for inhibition of perioperative inflammation.? Methods: A total of 40 breast cancer patients undergone the modified radical mastectomy were randomly divided into a parecoxib group (n=20) and a control group (n=20). The parecoxib group received intravenous parecoxib (40 mg, 5 mL) during general anesthesia induction, post-operative day 1 and day 2; the control group received intravenous normal saline (5 mL) at the corresponding time points. Their peripheral bloods were collected for routine test in the morning of the surgery day (T1), and Day 1 (T2), Day 3 (T3) and Day 7 (T4) after the surgery, and NLR was calculated.? Results: Compared with T1, NLR in the control group at T2 and T3 was significantly increased (P<0.05), but not at T4 (P>0.05); NLR in the parecoxib group was sharply increased at T2 (P<0.01), and returned to preoperative levels at T3 and T4 (P>0.05). NLR in the parecoxib group was significantly lower than that in the control group at T2 (P<0.05), but there were no significant difference between the two groups at other time points (P>0.05).? Conclusion: Parecoxib can restrain the inflammatory responses and improve immune function of the breast cancer patients by suppressing the elevation of NLR after the modified radical mastectomy, which is expected to improve the prognosis of the breast cancer patients. PMID- 28989151 TI - [Application of pie-crusting the medial collateral ligament release in arthroscopic surgery for posterior horn of ?medial meniscus in knee joint]. AB - OBJECTIVE: To explore the effectiveness and safety of pie-crusting the medial collateral ligament release (MCL) in treating posterior horn of medial meniscus (PHMM) tear in tight medial tibiofemoral compartment of knee joint.? Methods: Thirty-two consecutive patients with PHMM tear in tight medial tibiofemoral compartment of knee joint were admitted to our department from January, 2013 to December, 2014. All patients were performed pie-crusting the MCL release at its tibial insertion with 18-gauge intravenous needle. All patients were evaluated by valgus stress test and bilateral valgus stress radiograph at postoperative 1st day, 4th week and 12th week. Visual Analogue Scales (VAS), Lysholm scores, Tegner scores and International Knee Documentation Committee (IKDC) scores were recorded at the 1st, 3th, 6th month follow-up, then follow-up every 6 months.? Results: The mean follow-up was 28 (24-36) months. All cases were negative in valgus stress test. MCL rupture, femoral fracture, articular cartilage lesion and neurovascular injury were not found at the last follow-up. The median medial joint space width of affected side and unaffected side for valgus stress radiographs were 6.8 mm and 4.3 mm (P<0.05) at the 1st day, 5.5 mm and 4.2 mm ?(P<0.05) in the 4th week and 4.8 mm and 4.3 mm (P>0.05) at the 12th week, respectively. VAS scores was changed from 4.5+/-1.5 preoperatively to 1.7+/-1.0 at the final follow-up (t=16.561, P<0.05). Lysholm scores was changed from 52.3+/ 5.8 preoperatively to 93.2+/-6.3 at the final follow-up (t=-41.353, P<0.05). Tegner scores was changed from 4.1+/-1.1 preoperatively to 5.5+/-0.6 at the final follow-up (t=-18.792, P<0.05). IKDC scores was changed from 54.5+/-6.2 preoperative to 93.8+/-4.5 at the final follow-up (t=-38.253, P<0.05).? Conclusion: Pie-crusting the medial collateral ligament release is a safe, minimal invasive and effective surgical option for posterior horn of medial meniscus tear in tight medial tibiofemoral compartment of knee joint. PMID- 28989152 TI - [Correlations of FGF23 and Klotho with cardiovascular injury in chronic kidney disease patients]. AB - OBJECTIVE: To analyze the levels of serum calcium, phosphate, fibroblast growth factor 23 (FGF23), and Klotho proteins in patients with chronic kidney disease (CKD), and to investigate the correlations of FGF23 and Klotho proteins with cardiac complicates in patients with chronic kidney disease-mineral and bone disorder (CKD-MBD).? Methods: A total of 180 CKD-MBD patients were enrolled for this study. Among them, 60 patients underwent regular hemodialysis, 60 patients did not undergo renal replacement therapy and 60 patients were diagnosed as second hyperparathyroidism (SHPT). Thirty age and gender-matched health volunteers served as controls. Serum samples were collected and tested, and the demographical, clinical and biochemical data were all recorded. FGF23 and Klotho levels in serum samples were analyzed by enzyme-linked immunosorbent assay. Data of echocardiography and plain abdominal X rays were collected as well. The influential factors for cardiovascular injury, the relationship between biochemical indexes and ectopic calcification, and the correlations of FGF23 and Klotho with cardiac complicates were analyzed? Results: Patients, who kept hemodialysis, especially those with SHPT, exhibited an increase in serum FGF23 level while a decrease in serum Klotho protein levels (P<0.01). Patients with higher levels of serum FGF23 were more likely to have ectopic calcification (OR=4.667), while patients with lower levels of serum Klotho had high risks to get myocardial hypertrophy (OR=3.496). Receiver operator characteristic (ROC) curve analysis showed that the area under the curve (AUC) for FGF23 was 0.778 (P<0.01) while for Klotho was 0.715 (P<0.01).? Conclusion: Patients, who kept hemodialysis, especially those with SHPT, have a significant increase in serum FGF23 protein levels and a significant decrease in serum Klotho protein levels. Serum FGF23 and Klotho protein levels are closely correlated with left ventricular enlargement and hypertrophy. Serum FGF23 and Klotho protein are risk factors for heart. PMID- 28989153 TI - [Preoperational nutritional status for the children with congenital heart disease and the influential factors]. AB - OBJECTIVE: To investigate the preoperational nutritional condition for the children with congenital heart disease, and to analyze the relevant factors.? Methods: According to the standards of WHO, the Z-scores was used to assess the nutritional condition for the children, and the generational information questionnaire, State-Trait Anxiety Inventory, Self-Rating Depression Scale and Parent Understanding Questionnaire were used to analyze the maternal factors.? Results: Stunting, underweighting and wasting represented the poor nutritional conditions, which accounted for 28.6%, 25.3% and 25.3%, respectively. Maternal accurate perception and the psychological problems such as anxiety and depression were the main relevant factors.? Conclusion: The poor nutritional condition for the congenital heart disease was serious. It is very important to improve the maternal accurate perception and to relieve the maternal psychological problems for changing the nutritional condition through appropriate health education and effective intervention. PMID- 28989154 TI - [Influential factors associated with 2-week prevalence of fever and diarrhea among infants and young children at the age of 6-23 months in poor rural areas]. AB - OBJECTIVE: To investigate the status and influential factors associated with 2 week prevalence of fever and diarrhea among infants and young children at the age of 6-23 months in poor rural areas.? Methods: A total of 8 735 rural infants and young children aged 6-23 months in 30 poor counties of Wuling Mountains and Luoxiao Mountains in Hunan Province were selected in August 2015, and the questionnaires were used to collect information on the prevalence of fever and diarrhea, person and families, and feeding status. The data for prevalence of fever and diarrhea in infants and young children were calculated, and multi-non conditional logistic regression model were used to analyze the influential factors.? Results: The 2-week prevalence of fever and diarrhea in infants and young children was 20.8% and 12.2% respectively. The ages (OR=0.66, 95%CI 0.58 to 0.75), Dong ethnicity(OR=1.42, 95%CI 1.17 to 1.74) and low body weight (OR=1.31, 95%CI 1.11 to 1.54) were influential factors for fever among infants and young children in poor rural areas; female (OR=0.86, 95%CI 0.76 to 0.98), 12-17 months (OR=0.80, 95%CI 0.69 to 0.93), 18-23 months (OR=0.51, 95%CI 0.43 to 0.60), other ethnic minorities (OR=1.70, 95%CI 1.13 to 2.56), non-complementary feeding (OR=1.65, 95%CI 1.05 to 2.59) and low body weight (OR=1.39, 95%CI 1.14 to 1.70) were the influential factors of diarrhea among infants and young children.? Conclusion: The 2-week prevalence of fever and diarrhea among infants and young children aged 6-23 months in poor rural areas were quite serious. Low age, Dong ethnicity, and low birth weight are high risk factors for fever. Male, no addition of complementary feeding, and low birth weight are high risk factors for diarrhea. PMID- 28989155 TI - [Analysis of spatiotemporal patterns and influential factors for mushroom poisoning in Hunan Province in 2015]. AB - OBJECTIVE: To understand the spatial distribution of mushroom poisoning in Hunan Province and its influential factors, and to provide the evidence for control of the mushroom poisoning.? Methods: The surveillance data for mushroom poisoning cases from 122 counties in Hunan Province in 2015 were collected. Based on geographical information system database, spatial autocorrelation analysis and spatial regression analysis (via OpenGeoDa) was conducted.? Results: The incidence of mushroom poisoning in Hunan Province in 2015 was 2.94/100 000. Global Moran's I values was 0.315 (P<0.05). Local spatial autocorrelation analysis indicated that Ningxiang, Xiangtan, Shaoyang, Lingling, Jiahe, and Linwu districts et al were "positive hotspot" regions. Guzhang, Hecheng, Dingcheng, Yueyang districts et al were "negative hotspot" regions. Spatial regression analysis revealed that the reported incidence of mushroom poisoning was positively correlated with the annual average temperate (Z=2.145, P=0.032), the number of health care institutions per capita (Z=2.352, P=0.019), and the number of students enrollment in secondary schools (Z=4.309, P<0.001). It was negatively associated with the number of school staff and workers of secondary schools (Z= 2.626, P=0.009).? Conclusion: The spatial distribution of mushroom poisoning cases in Hunan Province in 2015 is highly clustered. Mushroom poisoning cases are more prevalent in the middle and southern regions and less prevalent in the northern areas of the province. The annual average temperate and the number of students enrollment in secondary schools demonstrate a certain positive influence on the distribution of mushroom poisoning in Hunan. PMID- 28989156 TI - [Prevalence and influential factors for asthma among adults in Chinese]. AB - OBJECTIVE: To analyze the prevalence and influential factors for asthma among adults in Chinese.? Methods: Chinese residents aged >=18 years in 12 regions were enrolled to estimate the prevalence of asthma in adults with different characteristics. Multivariate logistic regression analysis were adopted to determine the influential factors for asthma based on the China Health and Nutrition Survey in 2009 and 2011.? Results: The prevalence of asthma was 1.25% (95%CI 1.06% to 1.43%) among the entire adult population in China. There were significant differences in terms of age, gender, regions, city and countryside, smoking, body mass index (BMI), education levels, marriage and subjective well being (SWB)(all P<0.05). Compared with normal people, the risk of asthma complicated with hypertension, diabetes, myocardial infarction and stroke was significantly increased (P<0.01). The multiple logistic regression analysis showed that the influential factors for asthma included age (OR=1.042, 95%CI 1.032 to 1.053), gender (male OR=1.533, 95%CI 1.080 to 2.167), regions (Beijing OR=2.470, 95%CI 1.155 to 5.308), urban area (OR=1.355, 95%CI 1.026 to 1.786), BMI (OR=1.021, 95%CI 1.000 to 1.037), smoking (OR=1.428, 95%CI 1.028 to 1.989), drinking (OR=0.711, 95%CI 0.976), education level (OR=0.964, 95%CI 0.930 to 0.999), poor short-term health status (OR=5.295, 95%CI 4.055 to 6.934), well being (lowest OR=2.219, 95%CI 1.272 to 3.887), playing games (OR=2.732, 95%CI 1.023 to 6.088) and watching TV (OR=1.695, 95%CI 1.036 to 2.941).? Conclusion: Adult asthma is associated with multiple factors including age, gender, lifestyle, social environment, etc. PMID- 28989157 TI - [High-affinity glutamate transporters and chronic pain]. AB - Glutamate serves as a major excitatory neurotransmitter in the mammalian central nervous system and is stored in synaptic cleft by an uptake system that is dependent on the high-affinity glutamate transporters (ETTAs), which locate in the plasma membrane of glial cells and neurons. ETTAs can rapidly terminate the action of glutamate and maintain its normal physiological functions. If the content or function of glutamate transporters is abnormal, it can result in many physiological dysfunctions. Studies have demonstrated that high-affinity glutamate transporters play an important role in the development of chronic pain, which might be a new therapeutic target for the pain. PMID- 28989158 TI - [Environmental risk factors for induction of the inflammatory bowel disease]. AB - Inflammatory bowel disease (IBD) is a group of intestinal chronic non-specific inflammatory disease with unknown etiology, including ulcerative colitis and Crohn's disease. The risk factors associated with pathogenesis of IBD include environmental factors, genetic factors, and immune factors.Among them, the environmental factors include smoking, drugs, diet, infection and psychological factors. PMID- 28989159 TI - [Progress in study on animal models of ?chronic obstructive pulmonary disease]. AB - Chronic obstructive pulmonary disease (COPD) is an incompletely reversible chronic airway disease that can be prevented and cured. There is a tendency toward increasing the morbidity and mortality for COPD. Establishment of an animal model for COPD is an important step to explore the pathogenesis of this disease. Presently, a well-recognized COPD animal model is not available. The key points for establishing the COPD animal models, such as selection of animal species, parameters for model evaluation, are constantly updated. PMID- 28989160 TI - [Mechanism of migration and release of ?high mobility group box-1]. AB - High mobility group box-1 (HMGB1) is an evolutionarily conserved protein, which widely exists in mammals. HMGB1 contains the nucleus localization sequences. Intracellular and extracellular HMGB1 shows different biological functions. Extracellular HMGB1 is closely related to sepsis, cancer, rheumatoid immune, atherosclerosis, ischemia-reperfusion injury and so on. The mobilization of HMGB1 from the nucleus to the cytoplasm and subsequent release involves the processes of post-translation modification, active secretion and nuclear localization. PMID- 28989161 TI - [PET-CT imaging features of primary ureteric lymphoma: ?A case report and literature review]. AB - OBJECTIVE: To review the dual-time-point 18F-fluorodeoxyglucose (FDG) positron emission tomography/X-ray computed tomography (PET-CT) imaging for a patient with primary ureteric lymphoma (PUL), and explore the potential of FDG PET-CT on diagnosis, staging and evaluation of treatment in patients with PUL.? Methods: Complete clinical and imaging data of one patient with PUL was reported. The relevant literatures from 1997 to 2016 were reviewed, and the imaging features of uriteric lymphoma were analyzed.? Results: The patient presented with microhematuria, a soft-density mass with moderate enhancement in the mid left ureter, and a luminal stenosis with the scope inserted 5 cm into the left stoma, but no mass was found. The patient was pathologically diagnosed as follicular lymphoma (stage IE confirmed by whole body FDG PET-CT).? Conclusion: PET-CT may be useful in diagnosis, clinical stage and therapy assessment in patients with PUL. PMID- 28989164 TI - Editorial Note. PMID- 28989162 TI - [A case of pulmonary alternariosis complicated with aspergillosis]. AB - A 61-year-old woman with pulmonary alternariosis and aspergillosis was reported. The patient presented with recurrent hemoptysis and cough for 3 years. Alternaria was identified by fungal culture. Biopsy specimen showed pulmonary aspergillosis. The patient had been treated with voriconazole at 400 mg/d through intravenous guttae for 7 days, and then switched amphotericin B at 25 mg/d through intravenous guttae for 11 days. The patient was treated with voriconazole at ?400 mg through oral when she was discharged from hospital. After the treatment, the clinical symptoms of hemoptysis and cough were recovered, and the lung CT examinations showed normal. PMID- 28989165 TI - The Role of Doctors in Hunger Strikes. AB - In its Malta Declaration, The World Medical Association prohibits force-feeding of hunger strikers as "degrading and inhuman," even when this is the only way to save their lives. The European Court of Human Rights ruled that lifesaving force feeding is compatible with the state's duty to protect the lives of prisoners. To understand how such extreme divergence of opinions has become possible, this paper offers a critical examination of the social history of prisoners' hunger strikes, the philosophy of nonviolence, and the debate on its medicalization. The discourse by actors, professionals, regulators, and scholars on hunger strikes is divided into three paradigms: the "communicative," the "extreme violence," and the "psychiatric." I argue that another paradigm is in play, and its incorporation may enrich and balance the discourse. This is the "wounded combatant" paradigm, according to which hunger strikers are like enemy soldiers who are injured in battle. PMID- 28989166 TI - A Theoretical Foundation for the Ethical Distribution of Authorship in Multidisciplinary Publications. AB - In academia, authorship on publications confers merit as well as responsibility. The respective disciplines adhere to their "typical" authorship practices: individuals may be named in alphabetical order (e.g., in economics, mathematics), ranked in decreasing level of contribution (e.g., biomedical sciences), or the leadership role may be listed last (e.g., laboratory sciences). However, there is no specific, generally accepted guidance regarding authorship distribution in multidisciplinary teams, something that can lead to significant tensions and even conflict. Using Scanlon's contractualism as a basis, I propose a conceptual foundation for the ethical distribution of authorship in multidisciplinary teams; it features four relevant principles: desert, just recognition, transparency, and collegiality. These principles can serve in the development of a practical framework to support ethical and nonarbitrary authorship distribution, which hopefully would help reduce confusion and conflict, promote agreement, and contribute to synergy in multidisciplinary collaborative research. PMID- 28989167 TI - A Defense of The-Risks-of-Daily-Life. AB - Research examining the safe and effective treatment of diseases and disorders affecting children offers one of the best prospects for improving the medical treatment of children. But the inclusion of children in research raises difficult ethical questions, among them: To how much risk is it permissible to expose children in research? Various thresholds have been proposed to constrain research risks that do not offer children the prospect of direct medical benefit. These proposals include limiting research risks to (1) the risks of routine medical examinations, (2) the risks of participation in charitable activities, (3) the risks of family life, and (4) the risks-of-daily-life. I examine which, if any, of these proposals is defensible. I argue that only the risks-of-daily-life threshold is defensible and I offer a new justification for this risk threshold. I argue that the risks of daily life are justifiable because they are part of a reasonable trade-off between personal safety and our ability to pursue meaningful lives. PMID- 28989168 TI - (Queer) Family Values and "Reciprocal IVF": What Difference Does Sexual Identity Make? AB - In this paper I employ the case of "reciprocal IVF" (R-IVF)-in which a female female couple uses in vitro fertilization to allow one woman to be the genetic mother and the other the gestational mother of their child(ren)-to illuminate the role sexual identity might productively play in bioethics. Bioethicists who have taken up this issue have largely focused on the moral permissibility and availability of the technology, and so defend R-IVF through analogy to commonly accepted different-sex uses of IVF. In this way, they position sexual identity as largely irrelevant to the primary bioethical questions raised by R-IVF. My approach diverges on these counts as I focus on the ethics of R-IVF through the lens of queer family values specifically. I ask what the practice of R-IVF as an option might mean for the queer community at large, and so view sexual identity as integral to a full bioethical evaluation of the practice. PMID- 28989169 TI - Moyamoya Disease in an 18-Month-Old Female Caucasian Complicated by Cerebral Hyperperfusion Syndrome Following Indirect Revascularization. AB - BACKGROUND Cerebral hyperperfusion syndrome is a rare complication of indirect revascularization due to moyamoya disease, but has not been reported previously in the pediatric population. We present a case of an 18-month-old girl with moyamoya disease that was treated with bilateral pial synangiosis and had complications consistent with cerebral hyperperfusion syndrome. This case report discusses the pathophysiological mechanisms involved in cerebral hyperperfusion in moyamoya syndrome. CASE REPORT An 18-month-old female Caucasian presented with seizures and weakness of the left side. Angiography confirmed bilateral cerebral moyamoya disease that was worse on the right side. Indirect revascularization with pial synangiosis was first performed on the right side to allow for healing. Five months later, pial synangiosis was then performed on the left side. Postoperatively, the patient experienced increased intracranial pressure (ICP), suggesting cerebral hyperperfusion syndrome. She was treated with a repeat lumbar puncture, a lumbar drain, and a lumbar shunt. CONCLUSIONS This report demonstrates a case of cerebral hyperperfusion syndrome as a complication of moyamoya disease in a pediatric patient. Although the patient progressed well after placement of a lumbar shunt, this case demonstrates the occurrence of cerebral hyperperfusion syndrome as a complication of revascularization in pediatric patients and highlights the need for further research in this area. PMID- 28989170 TI - Olig2 Silence Ameliorates Cuprizone-Induced Schizophrenia-Like Symptoms in Mice. AB - BACKGROUND The pathogenesis of schizophrenia is complex and oligodendrocyte abnormality is an important component of the pathogenesis found in schizophrenia. This study was designed to evaluate the function of olig2 in cuprizone-induced schizophrenia-like symptoms in a mouse model, and to assess the related mechanisms. MATERIAL AND METHODS The schizophrenia-like symptoms were modeled by administration of cuprizone in mice. Open-field and elevated-plus maze tests were applied to detect behavioral changes. Adenovirus encoding olig2 siRNA was designed to silence olig2 expression. Real-time PCR and western blotting were applied to detect myelin basic protein (MBP), 2',3'-cyclic nucleotide 3' phosphodiesterase (CNPase), glial fibrillary acidic protein (GFAP) and olig2 expressions. RESULTS Open field test showed that the distance and time spent in the center area were significantly decreased in cuprizone mice (model mice) when compared with control mice (p<0.05). By contrast, olig2 silence could significantly increase the time and distance spent in the center area compared with the model mice (p<0.05). As revealed by elevated-plus maze test, the mice in the model group preferred the open arm and spent more time and distance in the open arm compared with control mice (p<0.05), while olig2 silence significantly reversed the abnormalities (p<0.05). Mechanically, MBP and CNPase expression were reduced in the model group compared with the control (p<0.05). However, olig2 silence reversed the reduction caused by cuprizone modeling (p<0.05). In addition, GFAP was elevated after cuprizone modeling compared with control (p<0.05), and was significantly inhibited by olig2 silence compared with model (p<0.05). CONCLUSIONS Cuprizone-induced schizophrenia-like symptoms involved olig2 upregulation. The silence of olig2 could prevent changes, likely through regulating MBP, CNPase, and GFAP expressions. PMID- 28989172 TI - Genome organization: Compartmentalizing chromatin without cohesin. PMID- 28989173 TI - Diabetic nephropathy: Renoprotective effects of GLP1R agonists and SGLT2 inhibitors. PMID- 28989171 TI - Convergence between biological, behavioural and genetic determinants of obesity. AB - Multiple biological, behavioural and genetic determinants or correlates of obesity have been identified to date. Genome-wide association studies (GWAS) have contributed to the identification of more than 100 obesity-associated genetic variants, but their roles in causal processes leading to obesity remain largely unknown. Most variants are likely to have tissue-specific regulatory roles through joint contributions to biological pathways and networks, through changes in gene expression that influence quantitative traits, or through the regulation of the epigenome. The recent availability of large-scale functional genomics resources provides an opportunity to re-examine obesity GWAS data to begin elucidating the function of genetic variants. Interrogation of knockout mouse phenotype resources provides a further avenue to test for evidence of convergence between genetic variation and biological or behavioural determinants of obesity. PMID- 28989174 TI - New treatment paradigms for ADPKD: moving towards precision medicine. AB - The natural history of autosomal dominant polycystic kidney disease (ADPKD) is characterized by a variable rate of cyst development and increase in total kidney volume (TKV), variable kidney function decline and age of onset of end-stage renal disease (ESRD), and variable presentation of renal and extrarenal manifestations. Precision medicine is proposed to improve patient outcomes by tailoring therapy to the specific genetic background, pathophysiology, disease burden, prognosis and status of each individual. This approach to the management of patients with ADPKD is nearing clinical implementation owing to advances in genetics, imaging, biomarker development and therapeutics. In this Review, we discuss pharmacological and non-pharmacological interventions for the treatment of hypertension and proteinuria, and for slowing the rate of cyst growth in patients with ADPKD before the development of ESRD. We provide recommendations for the management of renal complications, including cyst infection, nephrolithiasis, haematuria and chronic pain. The early treatment of patients with ADPKD who are largely asymptomatic is associated with a therapeutic burden but slows cyst growth and delays subsequent loss of kidney function, which ultimately delays the need for renal replacement therapy and has a positive effect on the quality of life of patients. PMID- 28989175 TI - Glomerular disease: Loss of Epas1 promotes FSGS. PMID- 28989176 TI - Renal physiology: ER-associated degradation in diabetes insipidus. PMID- 28989177 TI - [Cii] emission from L1630 in the Orion B molecular cloud. AB - CONTEXT: L1630 in the Orion B molecular cloud, which includes the iconic Horsehead Nebula, illuminated by the star system sigma Ori, is an example of a photodissociation region (PDR). In PDRs, stellar radiation impinges on the surface of dense material, often a molecular cloud, thereby inducing a complex network of chemical reactions and physical processes. AIMS: Observations toward L1630 allow us to study the interplay between stellar radiation and a molecular cloud under relatively benign conditions, that is, intermediate densities and an intermediate UV radiation field. Contrary to the well-studied Orion Molecular Cloud 1 (OMC1), which hosts much harsher conditions, L1630 has little star formation. Our goal is to relate the [Cii] fine-structure line emission to the physical conditions predominant in L1630 and compare it to studies of OMC1. METHODS: The [Cii] 158 MUm line emission of L1630 around the Horsehead Nebula, an area of 12' * 17', was observed using the upgraded German Receiver for Astronomy at Terahertz Frequencies (upGREAT) onboard the Stratospheric Observatory for Infrared Astronomy (SOFIA). RESULTS: Of the [Cii] emission from the mapped area 95%, 13 L?, originates from the molecular cloud; the adjacent Hii region contributes only 5%, that is, 1 L?. From comparison with other data (CO(1-0)-line emission, far-infrared (FIR) continuum studies, emission from polycyclic aromatic hydrocarbons (PAHs)), we infer a gas density of the molecular cloud of nH ~ 3 . 103 cm-3, with surface layers, including the Horsehead Nebula, having a density of up to nH ~ 4 . 104 cm-3. The temperature of the surface gas is T ~ 100 K. The average [Cii] cooling efficiency within the molecular cloud is 1.3 . 10-2. The fraction of the mass of the molecular cloud within the studied area that is traced by [Cii] is only 8%. Our PDR models are able to reproduce the FIR-[Cii] correlations and also the CO(1-0)-[Cii] correlations. Finally, we compare our results on the heating efficiency of the gas with theoretical studies of photoelectric heating by PAHs, clusters of PAHs, and very small grains, and find the heating efficiency to be lower than theoretically predicted, a continuation of the trend set by other observations. CONCLUSIONS: In L1630 only a small fraction of the gas mass is traced by [Cii]. Most of the [Cii] emission in the mapped area stems from PDR surfaces. The layered edge-on structure of the molecular cloud and limitations in spatial resolution put constraints on our ability to relate different tracers to each other and to the physical conditions. From our study, we conclude that the relation between [Cii] emission and physical conditions is likely to be more complicated than often assumed. The theoretical heating efficiency is higher than the one we calculate from the observed [Cii] emission in the L1630 molecular cloud. PMID- 28989179 TI - CO Emission from an Impinging Non-Premixed Flame. AB - Carbon monoxide (CO) results from the incomplete oxidation of hydrocarbon fuels. While CO can be desirable in some syngas processes, it is a dangerous emission from fires, gas heaters, gas stoves, or furnaces where insufficient oxygen in the core reaction prevents complete oxidation of fuel to carbon dioxide and water, particularly when the reaction is interrupted by interaction with relatively cool solid boundaries. This research examines the physico-thermo-chemical processes responsible for carbon monoxide release from a small laminar non-premixed methane/air flame impinging on a nearby surface. We measure the changes in CO emission as correlated with variations in flame structure observed using planar laser induced fluorescence (PLIF of OH and 2-photon CO), and two-line OH PLIF thermometry, as a function of burner-to-plate distance. In particular, this work combines the use of OH and CO PLIF, and PLIF thermometry to describe the relative locations of the CO rich region, the peak heat release zone as indicated by chemiluminescence and OH gradients, and the extended oxidative zone in the impinging flames. The results show that CO release correlates strongly with stagnating flow-driven changes in the location and extent of high concentration regions of OH in surface-impinging diffusion flames. PMID- 28989180 TI - Genetic isolation in an endemic African habitat specialist. AB - The Chestnut-banded Plover Charadrius pallidus is a Near-Threatened shorebird species endemic to mainland Africa. We examined levels of genetic differentiation between its two morphologically and geographically distinct subspecies, C. p. pallidus in southern Africa (population size 11 000-16 000) and C. p. venustus in eastern Africa (population size 6500). In contrast to other plover species that maintain genetic connectivity over thousands of kilometres across continental Africa, we found profound genetic differences between remote sampling sites. Phylogenetic network analysis based on four nuclear and two mitochondrial gene regions, and population genetic structure analyses based on 11 microsatellite loci, indicated strong genetic divergence, with 2.36% mitochondrial sequence divergence between individuals sampled in Namibia (southern Africa) and those of Kenya and Tanzania (eastern Africa). This distinction between southern and eastern African populations was also supported by highly distinct genetic clusters based on microsatellite markers (global FST = 0.309, GST' = 0.510, D = 0.182). Behavioural factors that may promote genetic differentiation in this species include habitat specialization, monogamous mating behaviour and sedentariness. Reliance on an extremely small number of saline lakes for breeding and limited dispersal between populations are likely to promote reproductive and genetic isolation between eastern and southern Africa. We suggest that the two Chestnut-banded Plover subspecies may warrant elevation to full species status. To assess this distinction fully, additional sample collection will be needed, with analysis of genetic and phenotypic traits from across the species' entire breeding range. PMID- 28989181 TI - International Peacekeeping Operations: Burden Sharing and Effectiveness. AB - This article takes stock of some of the important contributions to the study of peacekeeping (PK). Two key topics stand out: peacekeeping burden sharing and mission effectiveness. For burden sharing, the theoretical foundation is the private provision of public goods and joint products. Implications for burden sharing differ whether financial or troop contributions are being shared, with the latter driven by jointly produced country-specific benefits. Financial burden sharing can also differ between United Nations (UN)-led and non-UN-led peacekeeping operations, wherein country-specific benefits are especially important for the latter. Many articles gauge peacekeeping effectiveness by the mission's ability to maintain the peace or to protect lives for a set time period. More recently, multiple criteria are raised for evaluating peacekeeping in today's world of multifaceted peacebuilding operations. PMID- 28989182 TI - Spousal Bargaining Over Care for Elderly Parents in China: Imbalances in Sex Ratios Influence the Allocation of Support. AB - Using a unique Chinese survey of parents and adult children, this paper examines how married children negotiate with their spouses for time devoted to caring for their own parents. Applying a collective bargaining framework, I show that the sex ratio at marriage shifts household bargaining in favour of the husband's parents when women are less scarce, or against his parents when women are scarcer. Such changing dynamics in the family may potentially reverse the current preference for sons in China, implying that those with sons, rather than daughters, may be increasingly in need of state support. PMID- 28989183 TI - Romantic Relationship Commitment Behavior Among Emerging Adult African American Men. AB - Contextual and intrapersonal factors affecting the development of African American men's romantic relationship commitment-related behavior were investigated. Socioeconomic disadvantage during early adolescence was hypothesized to predict harsh, unsupportive parenting practices. Harsh parenting was hypothesized to result in youths' emotion-regulation difficulties, indicated by elevated levels of anger during mid-adolescence, particularly when men were exposed to racial discrimination. Young African American men's anger during mid adolescence, a consequence of harsh, unsupportive parenting and racial discrimination, was expected to predict commitment-related behavior. Hypotheses were tested with a sample of rural African American men participating in a panel study from the ages of 11 through 21. Data from teachers, parents, and youths were integrated into a multi-reporter measurement plan. Results confirmed the hypothesized associations. Study findings indicate that the combination of harsh parenting and racial discrimination is a powerful antecedent of young men's commitment-related behavior. Anger across mid-adolescence mediated this interaction effect. PMID- 28989185 TI - Optimal Proliferation and Differentiation of Chlamydia Trachomatis. AB - Chlamydia trachomatis is a bacterium that causes eye infection and blindness in humans. It has an unusual life cycle involving two developmental forms. Within a cytoplasmic inclusion, the reticulate body (RB) repeatedly divides by binary fission and asynchronously differentiates into the infectious elementary body (EB). Upon the death of the mammalian cell that host many such inclusions, only the EB form of the bacteria survive and proceed to infect other cells. Given the bacteria's fast spreading infection, conventional wisdom would have the few initial EB turn into RB, divide and proliferate first, and then eventually start converting in order to maximize the terminal EB population upon host cell lysis. Several biological processes are seen as possible mechanisms for implementing such a conversion strategy. However, the optimality of an instinctual strategy with a period of proliferate without conversion prior to the onset of differentiation has never been substantiated theoretically or justified mathematically. This paper formulates three relatively simple models that capture the essential features of the Chlamydia life cycle. When the initial infection is caused by the endocytosis of a small EB population well below the carrying capacity of the host cell, the Maximum Principle requires for these models an optimal conversion strategy that confirms and rigorously justifies the prevailing view of no conversion at the early stage of the host cell infection. However, the conventional supposition is found to be inappropriate for an initial EB (-to-RB) population near or above the carrying capacity. Previously suggested and new biological mechanisms are examined for their role in implementing the different optimal conversion strategies associated with models investigated herein. PMID- 28989184 TI - Sexual Minority Stress and Same-Sex Relationship Well-Being: A Meta-Analysis of Research Prior to the U.S. Nationwide Legalization of Same-Sex Marriage. AB - Meta-analytic methods were used to analyze 179 effect sizes retrieved from 32 research reports on the implications that sexual minority stress may have for same-sex relationship well-being. Sexual minority stress (aggregated across different types of stress) was moderately and negatively associated with same-sex relationship well-being (aggregated across different dimensions of relationship well-being). Internalized homophobia was significantly and negatively associated with same-sex relationship well-being, whereas heterosexist discrimination and sexual orientation visibility management were not. Moreover, the effect size for internalized homophobia was significantly larger than those for heterosexist discrimination and sexual orientation visibility management. Sexual minority stress was significantly and negatively associated with same-sex relationship quality but not associated with closeness or stability. Sexual minority stress was significantly and negatively associated with relationship well-being among same-sex female couples but not among same-sex male couples. The current status of research approaches in this field was also summarized and discussed. PMID- 28989186 TI - The Coupled Bio-Chemo-Electro-Mechanical Behavior of Glucose Exposed Arterial Elastin. AB - Elastin, the principle protein component of the elastic fiber, is a critical extracellular matrix (ECM) component of the arterial wall providing structural resilience and biological signaling essential in vascular morphogenesis and maintenance of mechanical homeostasis. Pathogenesis of many cardiovascular diseases have been associated with alterations of elastin. As a long-lived ECM protein that is deposited and organized before adulthood, elastic fibers can suffer from cumulative effects of biochemical exposure encountered during aging and/or disease, which greatly compromise their mechanical function. This review article covers findings from recent studies of the mechanical and structural contribution of elastin to vascular function, and the effects of biochemical degradation. Results from diverse experimental methods including tissue-level mechanical characterization, fiber-level nonlinear optical imaging, piezoelectric force microscopy, and nuclear magnetic resonance are reviewed. The intriguing coupled bio-chemo-electro-mechanical behavior of elastin calls for a multi-scale and multi-physical understanding of ECM mechanics and mechanobiology in vascular remodeling. PMID- 28989188 TI - How to Construct a Mixed Methods Research Design. AB - This article provides researchers with knowledge of how to design a high quality mixed methods research study. To design a mixed study, researchers must understand and carefully consider each of the dimensions of mixed methods design, and always keep an eye on the issue of validity. We explain the seven major design dimensions: purpose, theoretical drive, timing (simultaneity and dependency), point of integration, typological versus interactive design approaches, planned versus emergent design, and design complexity. There also are multiple secondary dimensions that need to be considered during the design process. We explain ten secondary dimensions of design to be considered for each research study. We also provide two case studies showing how the mixed designs were constructed. PMID- 28989189 TI - Mechanistic Kinetic Modeling of Thiol-Michael Addition Photopolymerizations via Photocaged "Superbase" Generators: An Analytical Approach. AB - A kinetic mechanism and the accompanying mathematical framework are presented for base-mediated thiol-Michael photopolymerization kinetics involving a photobase generator. Here, model kinetic predictions demonstrate excellent agreement with a representative experimental system composed of 2-(2-nitrophenyl)propyloxycarbonyl 1,1,3,3-tetramethylguanidine (NPPOC-TMG) as a photobase generator that is used to initiate thiol-vinyl sulfone Michael addition reactions and polymerizations. Modeling equations derived from a basic mechanistic scheme indicate overall polymerization rates that follow a pseudo-first-order kinetic process in the base and coreactant concentrations, controlled by the ratio of the propagation to chain-transfer kinetic parameters (kp/kCT) which is dictated by the rate-limiting step and controls the time necessary to reach gelation. Gelation occurs earlier as the kp/kCT ratio reaches a critical value, wherefrom gel times become nearly independent of kp/kCT. The theoretical approach allowed determining the effect of induction time on the reaction kinetics due to initial acid-base neutralization for the photogenerated base caused by the presence of protic contaminants. Such inhibition kinetics may be challenging for reaction systems that require high curing rates but are relevant for chemical systems that need to remain kinetically dormant until activated although at the ultimate cost of lower polymerization rates. The pure step-growth character of this living polymerization and the exhibited kinetics provide unique potential for extended dark-cure reactions and uniform material properties. The general kinetic model is applicable to photobase initiators where photolysis follows a unimolecular cleavage process releasing a strong base catalyst without cogeneration of intermediate radical species. PMID- 28989190 TI - The effect of pH, electrolytes and temperature on the rhizosphere geochemistry of phytosiderophores. AB - BACKGROUND AND AIMS: Graminaceous plants are grown worldwide as staple crops under a variety of climatic and soil conditions. They release phytosiderophores for Fe acquisition (Strategy II). Aim of the present study was to uncover how the rhizosphere pH, background electrolyte and temperature affect the mobilization of Fe and other metals from soil by phytosiderophores. METHODS: For this purpose a series of kinetic batch interaction experiments with the phytosiderophore 2' deoxymugineic acid (DMA), a calcareous clay soil and a mildly acidic sandy soil were performed. The temperature, electrolyte concentration and applied electrolyte cation were varied. The effect of pH was examined by applying two levels of lime and Cu to the acidic soil. RESULTS: Fe mobilization by DMA increased by lime application, and was negatively affected by Cu amendment. Mobilization of Fe and other metals decreased with increasing ionic strength, and was lower for divalent than for monovalent electrolyte cations at equal ionic strength, due to higher adsorption of metal-DMA complexes to the soil. Metal mobilization rates increased with increasing temperature leading to a faster onset of competition; Fe was mobilized faster, but also became depleted faster at higher temperature. Temperature also affected biodegradation rates of metal-DMA complexes. CONCLUSION: Rhizosphere pH, electrolyte type and concentration and temperature can have a pronounced effect on Strategy II Fe acquisition by affecting the time and concentration 'window of Fe uptake' in which plants can benefit from phytosiderophore-mediated Fe uptake. PMID- 28989187 TI - Physical models of collective cell motility: from cell to tissue. AB - In this article, we review physics-based models of collective cell motility. We discuss a range of techniques at different scales, ranging from models that represent cells as simple self-propelled particles to phase field models that can represent a cell's shape and dynamics in great detail. We also extensively review the ways in which cells within a tissue choose their direction, the statistics of cell motion, and some simple examples of how cell-cell signaling can interact with collective cell motility. This review also covers in more detail selected recent works on collective cell motion of small numbers of cells on micropatterns, in wound healing, and the chemotaxis of clusters of cells. PMID- 28989191 TI - Extensive validation of CM SAF surface radiation products over Europe. AB - This work presents a validation of three satellite-based radiation products over an extensive network of 313 pyranometers across Europe, from 2005 to 2015. The products used have been developed by the Satellite Application Facility on Climate Monitoring (CM SAF) and are one geostationary climate dataset (SARAH JRC), one polar-orbiting climate dataset (CLARA-A2) and one geostationary operational product. Further, the ERA-Interim reanalysis is also included in the comparison. The main objective is to determine the quality level of the daily means of CM SAF datasets, identifying their limitations, as well as analyzing the different factors that can interfere in the adequate validation of the products. The quality of the pyranometer was the most critical source of uncertainty identified. In this respect, the use of records from Second Class pyranometers and silicon-based photodiodes increased the absolute error and the bias, as well as the dispersion of both metrics, preventing an adequate validation of the daily means. The best spatial estimates for the three datasets were obtained in Central Europe with a Mean Absolute Deviation (MAD) within 8-13 W/m2, whereas the MAD always increased at high-latitudes, snow-covered surfaces, high mountain ranges and coastal areas. Overall, the SARAH-JRC's accuracy was demonstrated over a dense network of stations making it the most consistent dataset for climate monitoring applications. The operational dataset was comparable to SARAH-JRC in Central Europe, but lacked of the temporal stability of climate datasets, while CLARA-A2 did not achieve the same level of accuracy despite predictions obtained showed high uniformity with a small negative bias. The ERA-Interim reanalysis shows the by-far largest deviations from the surface reference measurements. PMID- 28989192 TI - Team-Based Professional Development Interventions in Higher Education: A Systematic Review. AB - Most professional development activities focus on individual teachers, such as mentoring or the use of portfolios. However, new developments in higher education require teachers to work together in teams more often. Due to these changes, there is a growing need for professional development activities focusing on teams. Therefore, this review study was conducted to provide an overview of what is known about professional development in teams in the context of higher education. A total of 18 articles were reviewed that describe the effects of professional development in teams on teacher attitudes and teacher learning. Furthermore, several factors that can either hinder or support professional development in teams are identified at the individual teacher level, at the team level, and also at the organizational level. PMID- 28989193 TI - The Effects of Mobile-Computer-Supported Collaborative Learning: Meta-Analysis and Critical Synthesis. AB - One of the trends in collaborative learning is using mobile devices for supporting the process and products of collaboration, which has been forming the field of mobile-computer-supported collaborative learning (mCSCL). Although mobile devices have become valuable collaborative learning tools, evaluative evidence for their substantial contributions to collaborative learning is still scarce. The present meta-analysis, which included 48 peer-reviewed journal articles and doctoral dissertations written over a 16-year period (2000-2015) involving 5,294 participants, revealed that mCSCL has produced meaningful improvements for collaborative learning, with an overall mean effect size of 0.516. Moderator variables, such as domain subject, group size, teaching method, intervention duration, and reward method were related to different effect sizes. The results provided implications for future research and practice, such as suggestions on how to appropriately use the functionalities of mobile devices, how to best leverage mCSCL through effective group learning mechanisms, and what outcome variables should be included in future studies to fully elucidate the process and products of mCSCL. PMID- 28989194 TI - Effective Dementia Education and Training for the Health and Social Care Workforce: A Systematic Review of the Literature. AB - Ensuring an informed and effective dementia workforce is of international concern; however, there remains limited understanding of how this can be achieved. This review aimed to identify features of effective dementia educational programs. Critical interpretive synthesis underpinned by Kirkpatrick's return on investment model was applied. One hundred and fifty-two papers of variable quality were included. Common features of more efficacious educational programs included the need for educational programs to be relevant to participants' role and experience, involve active face-to-face participation, underpin practice-based learning with theory, be delivered by an experienced facilitator, have a total duration of at least 8 hours with individual sessions of 90 minutes or more, support application of learning in practice, and provide a structured tool or guideline to guide care practice. Further robust research is required to develop the evidence base; however, the findings of this review have relevance for all working in workforce education. PMID- 28989195 TI - FAILURES-TO-LAUNCH AND BOOMERANG KIDS: CONTEMPORARY DETERMINANTS OF LEAVING AND RETURNING TO THE PARENTAL HOME. AB - The percentage of young American adults residing in their parents' home has increased markedly over recent years, but we know little about how sociodemographic, life-course, and parental characteristics facilitate or impede leaving or returning home. We use longitudinal data from the Panel Study of Income Dynamics' Transition into Adulthood survey to examine the determinants of leaving and returning home among youth who turned age 18 between 2005 and 2011. Findings from event history models show that while leaving and returning home is to some extent a function of normative life-course transitions, characteristics of the parental home (e.g., presence of co-resident siblings, mother's educational attainment) and the degree of family connectivity (e.g., emotional closeness to mother, instrumental help from family) also play important roles. Experiencing physical, including sexual, victimization drives young adults both out of, and back into, the parental home. Having parents in poor physical health encourages young adults to move back home. Overall, the results suggest that a comprehensive explanation for both home-leaving and home-returning will need to look beyond life-course transitions and standard economic accounts to encompass a broader array of push and pull factors, particularly those that bond young adults with their parents. PMID- 28989196 TI - Managing Boundaries: The Role of Non-Profit Organisations in Russia's Managed Democracy. AB - This article examines Russian human service non-profit organisations (NPOs) to investigate the nature of civil society in a managed democracy. Specifically the focus is on emerging vertical ties between NPOs and ruling and governing elites. Drawing on qualitative data collected from health and education NPOs in three industrial regions, we find that in establishing such vertical ties the role of organisations and individuals within is changing - they have moved away from ignored outsiders towards accessing the circles of power and being tasked with managing the boundary between the state and civil society. In exploring these arrangements this article highlights that in the post-Soviet space, NPOs and the state are closely intertwined resembling co-optation. As a result the democratisation potential of human service NPOs is constrained. In discussing these insights we also draw parallels to contexts in which the state has outsourced welfare service to human service NPOs. PMID- 28989197 TI - Enjoyment, Exploration and Education: Understanding the Consumption of Pornography among Young Men with Non-Exclusive Sexual Orientations. AB - This qualitative research examines the influence of pornography consumption on young men with non-exclusive sexual orientations. Drawing on 35 in-depth interviews with young men from an elite university in the north-eastern United States, we examine how pornography was experienced as a leisure activity to be consumed in free time. Rather than focusing on the potential harms of pornography, we use an inductive analytic approach to explore the broader range of experiences that participants had, since the time they first consumed pornography. We demonstrate that pornography had educational benefits for these young men, related to their sexual desires, emerging sexual identities and for developing new sexual techniques. This study is part of a growing body of research that seeks to develop a holistic understanding of pornography in society, addressing the absence of the lived experience of the consumer in most pornography research. PMID- 28989198 TI - 'Like Skydiving without a Parachute': How Class Origin Shapes Occupational Trajectories in British Acting. AB - There is currently widespread concern that access to, and success within, the British acting profession is increasingly dominated by those from privileged class origins. This article seeks to empirically interrogate this claim using data on actors from the Great British Class Survey (N = 404) and 47 qualitative interviews. First, survey data demonstrate that actors from working-class origins are significantly underrepresented within the profession. Second, they indicate that even when those from working-class origins do enter the profession they do not have access to the same economic, cultural and social capital as those from privileged backgrounds. Third, and most significantly, qualitative interviews reveal how these capitals shape the way actors can respond to shared occupational challenges. In particular we demonstrate the profound occupational advantages afforded to actors who can draw upon familial economic resources, legitimate embodied markers of class origin (such as Received Pronunciation) and a favourable typecasting. PMID- 28989199 TI - Wider-community Segregation and the Effect of Neighbourhood Ethnic Diversity on Social Capital: An Investigation into Intra-Neighbourhood Trust in Great Britain and London. AB - Extensive research has demonstrated that neighbourhood ethnic diversity is negatively associated with intra-neighbourhood social capital. This study explores the role of segregation and integration in this relationship. To do so it applies three-level hierarchical linear models to two sets of data from across Great Britain and within London, and examines how segregation across the wider community in which a neighbourhood is nested impacts trust amongst neighbours. This study replicates the increasingly ubiquitous finding that neighbourhood diversity is negatively associated with neighbour-trust. However, we demonstrate that this relationship is highly dependent on the level of segregation across the wider-community in which a neighbourhood is nested. Increasing neighbourhood diversity only negatively impacts neighbour-trust when nested in more segregated wider-communities. Individuals living in diverse neighbourhoods nested within integrated wider-communities experience no trust-penalty. These findings show that segregation plays a critical role in the neighbourhood diversity/trust relationship, and that its absence from the literature biases our understanding of how ethnic diversity affects social cohesion. PMID- 28989200 TI - Man Thou Art Dust: Rites of Passage in Austere Times. AB - In response to recent calls for further cross-disciplinary research on austerity and a deeper sociological understanding of the impact and aftermath of the economic crisis on individuals and societies, this article builds on extant austerity literature through an exploration of its effects on European men. Informed by theories of liminality and rites of passage, this qualitative investigation examines the experience of austerity from the perspective of 11 men through the three liminal stages of separation, transition and reaggregation and investigates its impact on their identity, responsibilities and expectations. Our findings reveal the negative experiences of alienation and outsiderhood alongside positive experiences of communitas, solidarity and comradeship. The study provides a nuanced understanding of modern male Europeans and their 'rites of passage' through austere times. PMID- 28989202 TI - Interpopulation variability and adaptive potential for reduced glyphosate sensitivity in Alopecurus myosuroides. AB - Glyphosate use in the United Kingdom has more than doubled in the last 20 years. Much of this increase is driven by efforts to control herbicide resistant weeds, particularly Alopecurus myosuroides, prior to crop drilling. There is precedent for evolution of glyphosate resistance in similar situations, raising concerns over the sustainability of glyphosate use in the UK. We used dose-response experiments to examine variation in glyphosate sensitivity amongst 40 field collected A. myosuroides populations. No populations were resistant to glyphosate, but ED 90 values ranged between 354 and 610 g a.i. ha-1. Five populations had ED 90 values significantly higher than the unexposed control population collected from a site at Rothamsted Research with no previous glyphosate exposure. Recurrent selection experiments were performed to determine whether variation in glyphosate sensitivity had a heritable basis. Following two rounds of selection, five of six field populations evolved significantly reduced sensitivity to glyphosate, with R/S ratios, based on estimated ED 50 values, ranging from 1.2 to 1.5. These results confirm that there is a heritable basis to variation in glyphosate sensitivity. The response to selection was modest. Evolved populations were not highly resistant to glyphosate, although some twice selected individuals survived recommended field rates. These results do not represent definitive proof of the potential of A. myosuroides to evolve glyphosate resistance, although they do indicate caution is needed when considering the sustainability of increased glyphosate use to control this herbicide resistance-prone species. PMID- 28989201 TI - Identification of an unexpected shunt pathway product provides new insights into tirandamycin biosynthesis. AB - Tirandamycin K (7), the first linear 7,13;9,13-diseco-tirandamycin derivative, was isolated from the tamI (encoding the TamI P450 monooxygenase) disruption mutant strain (DeltatamI) of marine Streptomyces sp. 307-9. Its chemical structure with relative and absolute configurations was elucidated by a combination of extensive spectroscopic analyses and biosynthetic inferences. Structural elucidation of this unusual compound provides new insights into tirandamycin biosynthesis. Moreover, examination of the biological activity of 7 confirms the essential function of the bicyclic ketal ring for antibiotic activities of tirandamycins. PMID- 28989203 TI - Bayesian sparse reduced rank multivariate regression. AB - Many modern statistical problems can be cast in the framework of multivariate regression, where the main task is to make statistical inference for a possibly sparse and low-rank coefficient matrix. The low-rank structure in the coefficient matrix is of intrinsic multivariate nature, which, when combined with sparsity, can further lift dimension reduction, conduct variable selection, and facilitate model interpretation. Using a Bayesian approach, we develop a unified sparse and low-rank multivariate regression method to both estimate the coefficient matrix and obtain its credible region for making inference. The newly developed sparse and low-rank prior for the coefficient matrix enables rank reduction, predictor selection and response selection simultaneously. We utilize the marginal likelihood to determine the regularization hyperparameter, so our method maximizes its posterior probability given the data. For theoretical aspect, the posterior consistency is established to discuss an asymptotic behavior of the proposed method. The efficacy of the proposed approach is demonstrated via simulation studies and a real application on yeast cell cycle data. PMID- 28989205 TI - The effectiveness of online, family-based media literacy education for substance abuse prevention in elementary school children: Study of the Media Detective Family program. AB - The present study investigates the effectiveness of a family-based, online media literacy education (MLE) program for substance abuse prevention in children from rural areas. A total of 83 families were randomly assigned to receive Media Detective Family (MDF) (n = 47) or a control computer program (n = 36) between pre- and posttest questionnaires. Fifty-one percent (N=42) completed a three month follow-up questionnaire. Children receiving MDF reported a significant reduction in their use of substances over time compared to children in the control group (d = -.80). Parents receiving MDF reported that the program was convenient and engaging. The current study showed that an online substance use prevention program using MLE and designed for families is an effective intervention method for reducing children's substance use. PMID- 28989204 TI - Association of IL-6 with PM2.5 Components: Importance of Characterizing Filter Based PM2.5 Following Extraction. AB - Filter-based toxicology studies are conducted to establish the biological plausibility of the well-established health impacts associated with fine particulate matter (PM2.5) exposure. Ambient PM2.5 collected on filters is extracted into solution for toxicology applications, but frequently, characterization is nonexistent or only performed on filter-based PM2.5, without consideration of compositional differences that occur during the extraction processes. To date, the impact of making associations to measured components in ambient instead of extracted PM2.5 has not been investigated. Filter-based PM2.5 was collected at locations (n = 5) and detailed characterization of both ambient and extracted PM2.5 was performed. Alveolar macrophages (AMJ2-C11) were exposed (3, 24, and 48 h) to PM2.5 and the pro-inflammatory cytokine interleukin (IL)-6 was measured. IL-6 release differed significantly between PM2.5 collected from different locations; surprisingly, IL-6 release was highest following treatment with PM2.5 from the lowest ambient concentration location. IL-6 was negatively correlated with the sum of ambient metals analyzed, as well as with concentrations of specific constituents which have been previously associated with respiratory health effects. However, positive correlations of IL-6 with extracted concentrations indicated that the negative associations between IL-6 and ambient concentrations do not accurately represent the relationship between inflammation and PM2.5 exposure. Additionally, seven organic compounds had significant associations with IL-6 release when considering ambient concentrations, but they were not detected in the extracted solution. Basing inflammatory associations on ambient concentrations that are not necessarily representative of in vitro exposures creates misleading results; this study highlights the importance of characterizing extraction solutions to conduct accurate health impact research. PMID- 28989206 TI - Pitted terrains on (1) Ceres and implications for shallow subsurface volatile distribution. AB - Prior to the arrival of the Dawn spacecraft at Ceres, the dwarf planet was anticipated to be ice-rich. Searches for morphological features related to ice have been ongoing during Dawn's mission at Ceres. Here we report the identification of pitted terrains associated with fresh Cerean impact craters. The Cerean pitted terrains exhibit strong morphological similarities to pitted materials previously identified on Mars (where ice is implicated in pit development) and Vesta (where the presence of ice is debated). We employ numerical models to investigate the formation of pitted materials on Ceres and discuss the relative importance of water ice and other volatiles in pit development there. We conclude that water ice likely plays an important role in pit development on Ceres. Similar pitted terrains may be common in the asteroid belt and may be of interest to future missions motivated by both astrobiology and in situ resource utilization. PMID- 28989208 TI - Ocean remote sensing for sustainable resources. PMID- 28989207 TI - Juno-UVS approach observations of Jupiter's auroras. AB - Juno ultraviolet spectrograph (UVS) observations of Jupiter's aurora obtained during approach are presented. Prior to the bow shock crossing on 24 June 2016, the Juno approach provided a rare opportunity to correlate local solar wind conditions with Jovian auroral emissions. Some of Jupiter's auroral emissions are expected to be controlled or modified by local solar wind conditions. Here we compare synoptic Juno-UVS observations of Jupiter's auroral emissions, acquired during 3-29 June 2016, with in situ solar wind observations, and related Jupiter observations from Earth. Four large auroral brightening events are evident in the synoptic data, in which the total emitted auroral power increases by a factor of 3-4 for a few hours. Only one of these brightening events correlates well with large transient increases in solar wind ram pressure. The brightening events which are not associated with the solar wind generally have a risetime of ~2 h and a decay time of ~5 h. PMID- 28989209 TI - Dampening, Positive Rumination, and Positive Life Events: Associations with Depressive Symptoms in Children at Risk for Depression. AB - Blunted positive affect is characteristic of depression. Altered positive affect regulation may contribute to this blunting, and two regulation strategies, dampening positive affect and positive rumination, have been implicated in depression. However, the conditions under which these strategies impart risk/protective effects prior to onset of depression are unknown. The current study examined 81 healthy children (age 7-10) at low and high risk for depression on the basis of maternal history of depression and tested how dampening and positive rumination interacted with the experience of recent positive life events to predict depressive symptoms. Children at high and low risk did not differ in their use of dampening or positive rumination. However, elevated use of dampening in the context of many positive life events predicted current depressive symptoms, and specifically anhedonic symptoms, in children at low-risk for depression. These findings held when controlling for negative rumination and negative life events. Positive rumination did not interact with positive life events but was associated with higher depressive symptoms in high-risk children. Results indicate that prior to the onset of depression, positive life events may impart risk when dampening positive affect is utilized in this context, while positive rumination may increase risk for depressive symptoms. PMID- 28989210 TI - The relationship between automatic thoughts and depression in a cognitive behavioral treatment for people living with HIV/AIDS: Exploring temporality and causality. AB - Depression in people living with HIV/AIDS (PLWHA) is highly prevalent and related to worse adherence to antiretroviral therapy, but is amenable to change via CBT. Cognitive-behavioral therapy for adherence and depression (CBT-AD) specifically addresses negative automatic thoughts (ATs) as one component of the treatment. There is little research on the temporal nature of the relation between ATs and depression. HIV-positive adults with depression (N=240) were randomized to CBT AD, information/supportive psychotherapy for adherence and depression (ISP-AD), or one session of adherence counseling alone (ETAU). ATs were self-reported (Automatic Thoughts Questionnaire; ATQ) and depression was assessed by blinded interview (Montgomery-Asberg Depression Rating Scale; MADRS) at baseline, and 4-, 8-, and 12-months. We performed autoregressive cross-lagged panel models. Broadly, decreases in ATs were followed by decreases in depression, but decreases in depression were not followed by decreases in ATs. In CBT-AD, decreases in ATs were followed by decreases in depression, and vice versa. However, in the ISP group, while depression and ATs both significantly influenced each other, not all relations were in the direction expected. This study adds to the evidence base for cognitive interventions to decrease depression in individuals with a chronic medical condition, HIV/AIDS. PMID- 28989211 TI - High Resolution Free Triiodothyronine-Thyrotropin (FT3-TSH) Responses to a Single Oral Dose of Liothyronine in Humans: Evidence of Distinct Inter-Individual Differences Unraveled Using an Electrical Network Model. AB - The effects of a single oral dose of liothyronine (L-T3) on thyroid stimulating hormone (TSH) and other related thyroid system parameters are partly understood despite therapeutic use of this hormone over many decades. We characterize individualized responses of the hypothalamus-pituitary-thyroid (HPT) axis and its related temporal hormonal profile using an electrical network model. Based on thyroid hormone responses from blood samples using a single 50 MUg oral dose of liothyronine in healthy persons with a normal operating euthyroid feedback HPT system, we derived an equivalent electrical circuit model for the system's responses. The mathematical model was tested with a circuit simulator and validated with individualized clinical data. This signal processing technique makes the evaluation of bioequivalence and bioavailability of various preparations of liothyronine at an individualized level a feasible endeavor for clinical application. PMID- 28989212 TI - Collegial Activity Learning between Heterogeneous Sensors. AB - Activity recognition algorithms have matured and become more ubiquitous in recent years. However, these algorithms are typically customized for a particular sensor platform. In this paper we introduce PECO, a Personalized activity ECOsystem, that transfers learned activity information seamlessly between sensor platforms in real time so that any available sensor can continue to track activities without requiring its own extensive labeled training data. We introduce a multi view transfer learning algorithm that facilitates this information handoff between sensor platforms and provide theoretical performance bounds for the algorithm. In addition, we empirically evaluate PECO using datasets that utilize heterogeneous sensor platforms to perform activity recognition. These results indicate that not only can activity recognition algorithms transfer important information to new sensor platforms, but any number of platforms can work together as colleagues to boost performance. PMID- 28989213 TI - Solvent extraction of Cu, Mo, V, and U from leach solutions of copper ore and flotation tailings. AB - Flotation tailings from copper production are deposits of copper and other valuable metals, such as Mo, V and U. New hydrometallurgical technologies are more economical and open up new possibilities for metal recovery. This work presents results of the study on the extraction of copper by mixed extractant consisting p-toluidine dissolved in toluene. The possibility of simultaneous liquid-liquid extraction of molybdenum and vanadium was examined. D2EHPA solutions was used as extractant, and recovery of individual elements compared for the representative samples of ore and copper flotation tailings. Radiometric methods were applied for process optimization. PMID- 28989214 TI - Extraction of pertechnetates from HNO3 solutions into ionic liquids. AB - The extraction of pertechnetate ions from aquous solutions containing various concentrations of nitric acid into hydrophobic ionic liquids (ILs) has been examined at 25, 50 and 70 degrees C. The results show that the distribution ratio of Tc (DTc) between both phases weakly depends on the temperature and HNO3 concentration when IL's with relatively short aliphatic chains are used. The DTc obtained for all examined ILs, except methyltrioctylammonium bis(trifluoromethylsulfonyl)imide and 1-butyl-3-methylimidasolium hexafluorophosphate, are lower than 1.5. In the case of methyltrioctylammonium bis(trifluoromethylsulfonyl)imide a decrease of Tc concentration in aqueous solutions facilitates pertechnetate extraction into the organic phase. PMID- 28989215 TI - The curious case of processing unaccusative verbs in aphasia. AB - BACKGROUND: Individuals with agrammatic Broca's aphasia (IWBA) exhibit a delay in lexical activation in S-V-O word order sentences and delayed lexical reactivation in sentences that contain syntactic dependencies. This pattern is in contrast to neurologically unimpaired individuals who immediately evince lexical reactivation at the gap in sentences that contain syntactic dependencies. However, in the case of sentences that contain unaccusative verbs, neurologically unimpaired individuals also exhibit a delay in lexical reactivation. This delay provides a unique opportunity to further examine lexical delays in IWBA. AIM: The purpose of the current studies is to investigate the online comprehension of sentences that contain unaccusative verbs in IWBA and in a group of age-matched control (AMC) individuals. METHODS AND PROCEDURES: Cross-modal picture priming was used to test for priming of a displaced lexical item (direct object noun) immediately after the unaccusative verb (at the gap) during the ongoing auditory stream and at three additional time points downstream from the verb (500 ms, 750 ms, and 1,250 ms). OUTCOMES AND RESULTS: Delayed reactivation of the displaced lexical item downstream from the gap (similar to prior reports of delayed reactivation with younger unimpaired listeners) for both the AMCs and the IWBA was found. CONCLUSION: These results provide support that IWBA do not evince a delayed time course of lexical reactivation for unaccusative verbs compared to neurologically unimpaired individuals. PMID- 28989216 TI - Rehabilitation Practitioners' Prioritized Care Processes in Hip Fracture Post Acute Care. AB - AIMS: Occupational and physical therapy in post-acute care (PAC) has reached the point where quality indicators for hip fracture are needed. This study characterizes the practitioners' prioritized hip fracture rehabilitation practices, which can guide future quality improvement initiatives. METHODS: Ninety-two practitioners participating in a parent mixed methods study were asked to rank a series of evidence-based best practices across five clinical domains (assessment, intervention, discharge planning, caregiver training and patient education). RESULTS: Prioritized practices reflected patient-practitioner collaboration, facilitating an effective discharge, and preventing adverse events. The highest endorsed care processes include: developing meaningful goals with patient input (84%) in assessment, using assistive devices in intervention (75%) and patient education (65%), engaging the patient and caregiver (50%) in discharge planning, and fall prevention (60%) in caregiver education. CONCLUSIONS: Practitioners identified key care priorities. This study lays the foundation for future work evaluating the extent to which these practices are delivered in PAC. PMID- 28989218 TI - Geometric Calibration Using Line Fiducials for Cone-Beam CT with General, Non Circular Source-Detector Trajectories. AB - PURPOSE: Traditional BB-based geometric calibration methods for cone-beam CT (CBCT) rely strongly on foreknowledge of the scan trajectory shape. This is a hindrance to the implementation of variable trajectory CBCT systems, normally requiring a dedicated calibration phantom or software algorithm for every scan orbit of interest. A more flexible method of calibration is proposed here that accommodates multiple orbit types - including strongly noncircular trajectories - with a single phantom and software routine. METHODS: The proposed method uses a calibration phantom consisting of multiple line-shaped wire segments. Geometric models relating the 3D line equations of the wires to the 2D line equations of their projections are used as the basis for system geometry estimation. This method was tested using a mobile C-arm CT system and comparisons were made to standard BB-based calibrations. Simulation studies were also conducted using a sinusoid-on-sphere orbit. Calibration performance was quantified in terms of Point Spread Function (PSF) width and back projection error. Visual image quality was assessed with respect to spatial resolution in trabecular bone in an anthropomorphic head phantom. RESULTS: The wire-based calibration method performed equal to or better than BB-based calibrations in all evaluated metrics. For the sinusoidal scans, the method provided reliable calibration, validating its application to non-circular trajectories. Furthermore, the ability to improve image quality using non-circular orbits in conjunction with this calibration method was demonstrated. CONCLUSION: The proposed method has been shown feasible for conventional circular CBCT scans and offers a promising tool for non-circular scan orbits that can improve image quality, reduce dose, and extend field of view. PMID- 28989217 TI - Epi-direction detected multimodal imaging of an unstained mouse retina with a Yb fiber laser. AB - In this work, we present all epi-direction detected images of an unstained mouse retina using multiphoton microscopy with a sub-50 fs Yb-fiber laser centered at 1.07 MUm. This wavelength is particularly interesting as the fundamental wavelength is transparent to the anterior segment of the eye and the higher harmonics are above DNA-damaging UV wavelengths. We present a characterization of the multimodal signals emitted from the different retinal layers, as well as from the choroid and the sclera. By characterizing native multiphoton signals from the retina, we move closer to having Yb-fiber considered for in vivo diagnosis of retinal disease through multiphoton microscopy as well as for corrective therapies. PMID- 28989219 TI - Task-Driven Orbit Design and Implementation on a Robotic C-Arm System for Cone Beam CT. AB - PURPOSE: This work applies task-driven optimization to the design of non-circular orbits that maximize imaging performance for a particular imaging task. First implementation of task-driven imaging on a clinical robotic C-arm system is demonstrated, and a framework for orbit calculation is described and evaluated. METHODS: We implemented a task-driven imaging framework to optimize orbit parameters that maximize detectability index d'. This framework utilizes a specified Fourier domain task function and an analytical model for system spatial resolution and noise. Two experiments were conducted to test the framework. First, a simple task was considered consisting of frequencies lying entirely on the fz-axis (e.g., discrimination of structures oriented parallel to the central axial plane), and a "circle + arc" orbit was incorporated into the framework as a means to improve sampling of these frequencies, and thereby increase task-based detectability. The orbit was implemented on a robotic C-arm (Artis Zeego, Siemens Healthcare). A second task considered visualization of a cochlear implant simulated within a head phantom, with spatial frequency response emphasizing high frequency content in the (fy , fz ) plane of the cochlea. An optimal orbit was computed using the task-driven framework, and the resulting image was compared to that for a circular orbit. RESULTS: For the fz -axis task, the circle + arc orbit was shown to increase d' by a factor of 1.20, with an improvement of 0.71 mm in a 3D edge-spread measurement for edges located far from the central plane and a decrease in streak artifacts compared to a circular orbit. For the cochlear implant task, the resulting orbit favored complementary views of high tilt angles in a 360 degrees orbit, and d' was increased by a factor of 1.83. CONCLUSIONS: This work shows that a prospective definition of imaging task can be used to optimize source-detector orbit and improve imaging performance. The method was implemented for execution of non-circular, task-driven orbits on a clinical robotic C-arm system. The framework is sufficiently general to include both acquisition parameters (e.g., orbit, kV, and mA selection) and reconstruction parameters (e.g., a spatially varying regularizer). PMID- 28989220 TI - High-resolution extremity cone-beam CT with a CMOS detector: Task-based optimization of scintillator thickness. AB - PURPOSE: CMOS x-ray detectors offer small pixel sizes and low electronic noise that may support the development of novel high-resolution imaging applications of cone-beam CT (CBCT). We investigate the effects of CsI scintillator thickness on the performance of CMOS detectors in high resolution imaging tasks, in particular in quantitative imaging of bone microstructure in extremity CBCT. METHODS: A scintillator thickness-dependent cascaded systems model of CMOS x-ray detectors was developed. Detectability in low-, high- and ultra-high resolution imaging tasks (Gaussian with FWHM of ~250 MUm, ~80 MUm and ~40 MUm, respectively) was studied as a function of scintillator thickness using the theoretical model. Experimental studies were performed on a CBCT test bench equipped with DALSA Xineos3030 CMOS detectors (99 MUm pixels) with CsI scintillator thicknesses of 400 MUm and 700 MUm, and a 0.3 FS compact rotating anode x-ray source. The evaluation involved a radiographic resolution gauge (0.6-5.0 lp/mm), a 127 MUm tungsten wire for assessment of 3D resolution, a contrast phantom with tissue mimicking inserts, and an excised fragment of human tibia for visual assessment of fine trabecular detail. RESULTS: Experimental studies show ~35% improvement in the frequency of 50% MTF modulation when using the 400 MUm scintillator compared to the standard nominal CsI thickness of 700 MUm. Even though the high-frequency DQE of the two detectors is comparable, theoretical studies show a 14% to 28% increase in detectability index (d'2) of high- and ultrahigh resolution tasks, respectively, for the detector with 400 MUm CsI compared to 700 MUm CsI. Experiments confirm the theoretical findings, showing improvements with the adoption of 400 MUm panel in the visibility of the radiographic pattern (2* improvement in peak-to-through distance at 4.6 lp/mm) and a 12.5% decrease in the FWHM of the tungsten wire. Reconstructions of the tibial plateau reveal enhanced visibility of trabecular structures with the CMOS detector with 400 MUm scinitllator. CONCLUSION: Applications on CMOS detectors in high resolution CBCT imaging of trabecular bone will benefit from using a thinner scintillator than the current standard in general radiography. The results support the translation of the CMOS sensor with 400 MUm CsI onto the clinical prototype of CMOS-based extremity CBCT. PMID- 28989221 TI - Deformable 3D-2D Registration for Guiding K-Wire Placement in Pelvic Trauma Surgery. AB - Pelvic Kirschner wire (K-wire) insertion is a challenging surgical task requiring interpretation of complex 3D anatomical shape from 2D projections (fluoroscopy) and delivery of device trajectories within fairly narrow bone corridors in proximity to adjacent nerves and vessels. Over long trajectories (~10-25 cm), K wires tend to curve (deform), making conventional rigid navigation inaccurate at the tip location. A system is presented that provides accurate 3D localization and guidance of rigid or deformable surgical devices ("components" - e.g., K wires) based on 3D-2D registration. The patient is registered to a preoperative CT image by virtually projecting digitally reconstructed radiographs (DRRs) and matching to two or more intraoperative x-ray projections. The K-wire is localized using an analogous procedure matching DRRs of a deformably parametrized model for the device component (deformable known-component registration, or dKC-Reg). A cadaver study was performed in which a K-wire trajectory was delivered in the pelvis. The system demonstrated target registration error (TRE) of 2.1 +/- 0.3 mm in location of the K-wire tip (median +/- interquartile range, IQR) and 0.8 +/- 1.4 degrees in orientation at the tip (median +/- IQR), providing functionality analogous to surgical tracking/navigation using imaging systems already in the surgical arsenal without reliance on a surgical tracker. The method offers quantitative 3D guidance using images (e.g., inlet/outlet views) already acquired in the standard of care, potentially extending the advantages of navigation to broader utilization in trauma surgery to improve surgical precision and safety. PMID- 28989222 TI - Ultra-miniature wireless temperature sensor for thermal medicine applications. AB - This study presents a prototype design of an ultra-miniature, wireless, battery less, and implantable temperature-sensor, with applications to thermal medicine such as cryosurgery, hyperthermia, and thermal ablation. The design aims at a sensory device smaller than 1.5 mm in diameter and 3 mm in length, to enable minimally invasive deployment through a hypodermic needle. While the new device may be used for local temperature monitoring, simultaneous data collection from an array of such sensors can be used to reconstruct the 3D temperature field in the treated area, offering a unique capability in thermal medicine. The new sensory device consists of three major subsystems: a temperature-sensing core, a wireless data-communication unit, and a wireless power reception and management unit. Power is delivered wirelessly to the implant from an external source using an inductive link. To meet size requirements while enhancing reliability and minimizing cost, the implant is fully integrated in a regular foundry CMOS technology (0.15 MUm in the current study), including the implant-side inductor of the power link. A temperature-sensing core that consists of a proportional-to absolute-temperature (PTAT) circuit has been designed and characterized. It employs a microwatt chopper stabilized op-amp and dynamic element-matched current sources to achieve high absolute accuracy. A second order sigma-delta (Sigma Delta) analog-to-digital converter (ADC) is designed to convert the temperature reading to a digital code, which is transmitted by backscatter through the same antenna used for receiving power. A high-efficiency multi-stage differential CMOS rectifier has been designed to provide a DC supply to the sensing and communication subsystems. This paper focuses on the development of the all-CMOS temperature sensing core circuitry part of the device, and briefly reviews the wireless power delivery and communication subsystems. PMID- 28989223 TI - Investigation of certain physical-chemical features of oil recovery by an optimized alkali-surfactant-foam (ASF) system. AB - The objective of this study is to discover a synergistic effect between foam stability in bulk and micro-emulsion phase behaviour to design a high-performance chemical system for an optimized alkaline-surfactant-foam (ASF) flooding for enhanced oil recovery (EOR). The focus is on the interaction of ASF chemical agents with oil in the presence and absence of a naphthenic acid component and in situ soap generation under bulk conditions. To do so, the impact of alkalinity, salinity, interfacial tension (IFT) reduction and in situ soap generation was systematically studied by a comprehensive measurement of (1) micro-emulsion phase behaviour using a glass tube test method, (2) interfacial tension and (3) foam stability analysis. The presented alkali-surfactant (AS) formulation in this study lowered IFT between the oil and aqueous phases from nearly 30 to 10-1-10-3 mN/m. This allows the chemical formulation to create considerably low IFT foam flooding with a higher capillary number than conventional foam for displacing trapped oil from porous media. Bulk foam stability tests demonstrated that the stability of foam diminishes in the presence of oil with large volumes of in situ soap generation. At lower surface tensions (i.e. larger in situ soap generation), the capillary suction at the plateau border is smaller, thus uneven thinning and instabilities of the film might happen, which will cause acceleration of film drainage and lamellae rupture. This observation could also be interpreted by the rapid spreading of oil droplets that have a low surface tension over the lamella. The spreading oil, by augmenting the curvature radius of the bubbles, decreases the surface elasticity and surface viscosity. Furthermore, the results obtained for foam stability in presence of oil were interpreted in terms of phenomenological theories of entering/spreading/bridging coefficients and lamella number. PMID- 28989224 TI - Semi-batch synthesis of colloidal spheres with fluorinated cores and varying grafts of poly(ethylene glycol). AB - Fluorinated spheres with grafted poly(ethylene glycol) (PEG) have been synthesized using a semi-batch emulsion polymerization in which the initiator is fed slowly to the reaction. In this way, PEG-grafted colloidal spheres can be fabricated with varying PEG chain length, different cores and varying degrees of crosslinking. The resulting batches have been characterized using disc centrifuge photosedimentometry and small-angle X-ray scattering. The size distribution is shown to be a sensitive function of the molar ratio of the reactive PEG macromonomer to fluorinated monomer, and with some optimization latices of very low polydispersity can be obtained with this simple synthesis method. For short PEG grafts too high a molar ratio results in a build up of smaller size particles and a broadening of the size distribution, whereas for longer grafts the mean particle size increases with decreasing molar ratio. PMID- 28989225 TI - Heavy-tailed fractional Pearson diffusions. AB - We define heavy-tailed fractional reciprocal gamma and Fisher-Snedecor diffusions by a non-Markovian time change in the corresponding Pearson diffusions. Pearson diffusions are governed by the backward Kolmogorov equations with space-varying polynomial coefficients and are widely used in applications. The corresponding fractional reciprocal gamma and Fisher-Snedecor diffusions are governed by the fractional backward Kolmogorov equations and have heavy-tailed marginal distributions in the steady state. We derive the explicit expressions for the transition densities of the fractional reciprocal gamma and Fisher-Snedecor diffusions and strong solutions of the associated Cauchy problems for the fractional backward Kolmogorov equation. PMID- 28989226 TI - Oviposition preference and offspring performance in container breeding mosquitoes: evaluating the effects of organic compounds and laboratory colonisation. AB - The preference-performance hypothesis predicts that organisms lacking parental care should oviposit in habitats that optimize offspring performance. We investigated preference-performance relationships for the Asian tiger mosquito (Aedes albopictus Skuse) and the southern house mosquito (Culex quinquefasciatus Say) (Diptera:Culicidae), two medically important container-breeding species, in response to an organic chemical blend mimicking decaying plant matter. Additionally, we evaluated the effects of long-term laboratory colonization of Cx. quinquefasciatus by using wild and laboratory strains.Oviposition bioassays were conducted by releasing gravid mosquitoes into field enclosures with automobile tires containing low and high concentrations of the chemical blend, and water controls. The offspring were then reared in water collected from the tires in which they were deposited.Aedes albopictus and wild Cx. quinquefasciatus laid more eggs in the chemical blend than water controls but did not differentiate between the low and high concentrations. Conversely, laboratory Cx. quinquefasciatus only preferred the high concentration to the low concentration. No statistical associations between oviposition preference and larval survival were found, as the chemical blend did not affect survivorship of either species.The oviposition preference for the chemical blend over water controls suggests that both species oviposit in the best available resource environment, but further studies are needed before conclusions regarding preference performance relationships can be drawn.We found that long-term laboratory colonization affects oviposition behavior in Cx. quinquefasciatus, suggesting that behavioral studies on laboratory strains are not always applicable to wild populations. PMID- 28989227 TI - Smell or vision? The use of different sensory modalities in predator discrimination. AB - ABSTRACT: Theory predicts that animals should adjust their escape responses to the perceived predation risk. The information animals obtain about potential predation risk may differ qualitatively depending on the sensory modality by which a cue is perceived. For instance, olfactory cues may reveal better information about the presence or absence of threats, whereas visual information can reliably transmit the position and potential attack distance of a predator. While this suggests a differential use of information perceived through the two sensory channels, the relative importance of visual vs. olfactory cues when distinguishing between different predation threats is still poorly understood. Therefore, we exposed individuals of the cooperatively breeding cichlid Neolamprologus pulcher to a standardized threat stimulus combined with either predator or non-predator cues presented either visually or chemically. We predicted that flight responses towards a threat stimulus are more pronounced if cues of dangerous rather than harmless heterospecifics are presented and that N. pulcher, being an aquatic species, relies more on olfaction when discriminating between dangerous and harmless heterospecifics. N. pulcher responded faster to the threat stimulus, reached a refuge faster and entered a refuge more likely when predator cues were perceived. Unexpectedly, the sensory modality used to perceive the cues did not affect the escape response or the duration of the recovery phase. This suggests that N. pulcher are able to discriminate heterospecific cues with similar acuity when using vision or olfaction. We discuss that this ability may be advantageous in aquatic environments where the visibility conditions strongly vary over time. SIGNIFICANCE STATEMENT: The ability to rapidly discriminate between dangerous predators and harmless heterospecifics is crucial for the survival of prey animals. In seasonally fluctuating environment, sensory conditions may change over the year and may make the use of multiple sensory modalities for heterospecific discrimination highly beneficial. Here we compared the efficacy of visual and olfactory senses in the discrimination ability of the cooperatively breeding cichlid Neolamprologus pulcher. We presented individual fish with visual or olfactory cues of predators or harmless heterospecifics and recorded their flight response. When exposed to predator cues, individuals responded faster, reached a refuge faster and were more likely to enter the refuge. Unexpectedly, the olfactory and visual senses seemed to be equally efficient in this discrimination task, suggesting that seasonal variation of water conditions experienced by N. pulcher may necessitate the use of multiple sensory channels for the same task. PMID- 28989228 TI - Effects of Maternal Work Incentives on Teen Drug Arrests. AB - PURPOSE: This study exploits differences in the implementation of welfare reform across states and over time in the United States in the attempt to identify causal effects of welfare reform on youth arrests for drug-related crimes between 1990 and 2005, the period during which welfare reform unfolded. METHODOLOGY: Using monthly arrest data from the U.S. Federal Bureau of Investigation's Uniform Crime Reports, we estimate the effects of welfare reform implementation on drug related arrests among 15-17 year olds in the United States between 1990 and 2005. We use a difference-in-differences (DD) approach that exploits the implementation of welfare reform across states and over time to estimate effects for teens exposed to welfare reform. FINDINGS: The findings, based on numerous different model specifications, suggest that welfare reform had no statistically significant effect on teen drug arrests. Most estimates were positive and suggestive of a small (3%) increase in arrests. ORIGINALITY/VALUE: This study investigated the effects of a broad-based policy change that altered maternal employment, family income, and other family characteristics on youth drug arrests. PMID- 28989229 TI - Impacts of extension access and cooperative membership on technology adoption and household welfare. AB - This paper examines the impacts of access to extension services and cooperative membership on technology adoption, asset ownership and poverty using household level data from rural Nigeria. Using different matching techniques and endogenous switching regression approach, we find that both extension access and cooperative membership have a positive and statistically significant effect on technology adoption and household welfare. Moreover, we find that both extension access and cooperative membership have heterogeneous impacts. In particular, we find evidence of a positive selection as the average treatment effects of extension access and cooperative membership are higher for farmers with the highest propensity to access extension and cooperative services. The impact of extension services on poverty reduction and of cooperatives on technology adoption is significantly stronger for smallholders with access to formal credit than for those without access. This implies that expanding rural financial markets can maximize the potential positive impacts of extension and cooperative services on farmers' productivity and welfare. PMID- 28989230 TI - Delivering Parent-Teen Therapy for ADHD through Videoconferencing: A Preliminary Investigation. AB - Adolescents with ADHD demonstrate notoriously poor treatment utilization. Barriers to access have been partially addressed through tailored therapy content and therapist delivery style; yet, additional challenges to engaging this population remain. To leverage modern technology in support of this aim, the current study investigates parent-teen therapy for ADHD delivered over a videoconferencing format. In this preliminary feasibility study, teens and parents (N=20) received an empirically supported dyadic therapy that incorporates skills-based modules with motivational interviewing. The videoconferencing interface was deemed feasible with nearly all families completing treatment. Acceptable therapeutic alliance was reported and key mechanisms of change were engaged (i.e., adolescent motivation to meet goals, parent strategy implementation). Families reported high satisfaction, despite minor disturbances associated with delivering therapy via videoconferencing. Treatment integrity and fidelity were acceptable, though slightly reduced compared to clinic-based trials of the same protocol. Therapists perceived that videoconferencing enhanced treatment for 50% of families. Reductions in participant ADHD symptoms and organization, time management, and planning problems from baseline to post treatment were noted by parents and teachers. However, open trial results of this study should be interpreted with caution due to their uncontrolled and preliminary nature. PMID- 28989231 TI - Controls on the distribution of fluorescent dissolved organic matter during an under-ice algal bloom in the western Arctic Ocean. AB - In this study we used fluorescence excitation and emission matrix spectroscopy, hydrographic data, and a self-organizing map (SOM) analysis to assess the spatial distribution of labile and refractory fluorescent dissolved organic matter (FDOM) for the Chukchi and Beaufort Seas at the time of a massive under-ice phytoplankton bloom during early summer 2011. Biogeochemical properties were assessed through decomposition of water property classes and sample classification that employed a SOM neural network-based analysis which classified 10 clusters from 269 samples and 17 variables. The terrestrial, humic-like component FDOM (ArC1, 4.98 +/- 1.54 Quinine Sulfate Units (QSU)) and protein-like component FDOM (ArC3, 1.63 +/- 0.88 QSU) were found to have elevated fluorescence in the Lower Polar Mixed Layer (LPML) (salinity ~29.56 +/- 0.76). In the LPML water mass, the observed contribution of meteoric water fraction was 17%, relative to a 12% contribution from the sea ice melt fraction. The labile ArC3 protein-like component (2.01 +/- 1.92 QSU) was also observed to be elevated in the Pacific Winter Waters mass, where the under-ice algal bloom was observed (~40 50 m). We interpreted these relationships to indicate that the accumulation and variable distribution of the protein-like component on the shelf could be influenced directly by sea ice melt, transport, and mixing processes and indirectly by the in situ algal bloom and microbial activity. ArC5, corresponding to what is commonly considered marine humic FDOM, indicated a bimodal distribution with high values in both the freshest and saltiest waters. The association of ArC5 with deep, dense salty water is consistent with this component as refractory humic-like FDOM, whereas our evidence of a terrestrial origin challenges this classic paradigm for this component. PMID- 28989232 TI - Setting Directions: Anisotropy in Hierarchically Organized Porous Silica. AB - Structural hierarchy, porosity, and isotropy/anisotropy are highly relevant factors for mechanical properties and thereby the functionality of porous materials. However, even though anisotropic and hierarchically organized, porous materials are well known in nature, such as bone or wood, producing the synthetic counterparts in the laboratory is difficult. We report for the first time a straightforward combination of sol-gel processing and shear-induced alignment to create hierarchical silica monoliths exhibiting anisotropy on the levels of both, meso- and macropores. The resulting material consists of an anisotropic macroporous network of struts comprising 2D hexagonally organized cylindrical mesopores. While the anisotropy of the mesopores is an inherent feature of the pores formed by liquid crystal templating, the anisotropy of the macropores is induced by shearing of the network. Scanning electron microscopy and small-angle X-ray scattering show that the majority of network forming struts is oriented towards the shearing direction; a quantitative analysis of scattering data confirms that roughly 40% of the strut volume exhibits a preferred orientation. The anisotropy of the material's macroporosity is also reflected in its mechanical properties; i.e., the Young's modulus differs by nearly a factor of 2 between the directions of shear application and perpendicular to it. Unexpectedly, the adsorption-induced strain of the material exhibits little to no anisotropy. PMID- 28989233 TI - Extremely Slow Spontaneous Electron Trapping in Photodoped n-Type CdSe Nanocrystals. AB - The trapping dynamics of conduction-band electrons in colloidal degenerately doped n-CdSe nanocrystals prepared by photochemical reduction (photodoping) were measured by direct optical methods. The nanocrystals show spontaneous electron trapping with distributed kinetics that extend to remarkably long timescales. Shifts in nanocrystal band-edge potentials caused by quantum confinement and surface ion stoichiometry were also measured by spectroelectrochemical techniques, and their relationship to the slow electron trapping is discussed. The very long electron-trapping timescales observed in these measurements are more consistent with atomic rearrangement than with fundamental electron-transfer processes. Such slow and broadly distributed electron-trapping dynamics are reminiscent of the well-known distributed dynamics of nanocrystal photoluminescence blinking, and potential relationships between the two phenomena are discussed. PMID- 28989234 TI - Valuing Air Quality Using Happiness Data: The Case of China. AB - This paper estimates the monetary value of cutting PM2.5, a dominant source of air pollution in China. By matching hedonic happiness in a nationally representative survey with daily air quality data according to the dates and counties of interviews in China, we are able to estimate the relationship between local concentration of particulate matter and individual happiness. By holding happiness constant, we calculate the tradeoff between the reduction in particulate matter and income, essentially a happiness-based measure of willingness-to-pay for mitigating air pollution. We find that people on average are willing to pay Y258 ($42, or 1.8% of annual household per capita income) per year per person for a 1% reduction in PM2.5. PMID- 28989236 TI - Alar cartilage-an alternative for spreader graft in primary rhinoplasty. AB - BACKGROUND: Alar cartilage can be very useful for tip and dorsum grafts. Depending on its size and thickness, it can be an important alternative for spreader grafts to improve endonasal functional deficiencies, correct deviated noses, and prevent inverted "V" deformities. Caucasian patients with bulbous tips are the most common candidates to achieve such benefits. It is easy to obtain and to frame into a desired graft. METHODS: The authors describe a surgical technique using the alar cartilages as spreader grafts. All Caucasian patients with bulbous tips who underwent primary rhinoplasty were included. All patients have been evaluated after 3 to 4 months and after 1 and 2 years by aesthetical and functional criteria. RESULTS: Thirty-four patients (28 female and 6 male) underwent this procedure between 2001 and 2015: 94% reported a better airflow, 91% reported very good aesthetic results and were very satisfied 2 years postoperatively, and 12% had nasal deviations that were corrected with a one side double-layered spreader grafts. Two patients presented supra-tip deformities and one patient had a columella scar that was revised surgically. No cases of inverted "V" deformity were reported 2 years postoperatively. CONCLUSIONS: Patients with functional satisfaction and with a straight and smooth dorsum seem to be the most important benefits that were achieved with this technique using alar cartilage spreader grafts, an alternative that can be offered to improve airflow and to prevent deviated and inverted "V" deformities. Level of Evidence: IV, therapeutic study. PMID- 28989235 TI - A new treatment for reliable functional and esthetic outcome after local facial flap reconstruction: a transparent polycarbonate facial mask with silicone sheeting. AB - BACKGROUND: Facial flap surgery predominantly leads to good functional results. However, in some cases, it can cause unsatisfactory esthetic results. They include persistent erythema, pincushioning, and development of hypertrophic scars. Conservative, reliable treatment for facial flaps is lacking. Pressure and silicone therapy have proven to result in significant improvement in scar erythema, pliability, and thickness in postburn hypertrophic scars. By combining these therapies in a facial mask, the esthetic outcome of facial flaps could be improved. In this retrospective study, the efficacy of a unique transparent face mask containing silicone sheets on the esthetic outcome of postsurgical facial flaps is assessed. METHODS: Twenty-one patients were assigned to facial pressure mask therapy after they underwent facial flap surgery between July 2012 and September 2015. Patients were treated for a mean duration of 46 weeks. The effects of pressure mask therapy were examined by means of the Patient and Observer Scar Assessment Scale (POSAS). RESULTS: All POSAS components showed a reduction between start and end of therapy, while itchiness, pigmentation, pliability, thickness, and relief of the flap improved significantly (P < 0.05). Mean total and patient score showed significant reduction between start and end of therapy. CONCLUSIONS: This study shows that a facial pressure mask layered with silicone results in noticeable flap improvement with a long-lasting result. Level of Evidence: Level III, therapeutic study. PMID- 28989238 TI - Hand rejuvenation with fat grafting: A 12-year single-surgeon experience. AB - BACKGROUND: Fat grafting has been successfully used for reconstructive and esthetic surgery of the breast, face, and other body parts. In this article, we present our protocol for hand fat grafting and over a decade of clinical experience. METHODS: Fat tissue is obtained from the flanks, peri-umbilical region, or internal side of the thigh or knee. No centrifuge machine is used to prevent fat damage. After decantation, fat is injected into the dorsum of the hand using a cannula from the wrist and not from the fingers. Fat is distributed gently above the dorsal deep fascia to avoid perforation of the vessels. RESULTS: The proposed technique was applied to 65 patients. The amount of fat injected ranged from 10 to 30 cm3. No allergic reactions were noticed. Each patient's progress was followed-up for a minimum of 12 months. Over this period, contour changes and the effects of the procedure(s) on the skin were analyzed. Fifty-six patients (84%) were satisfied with the results during the observation period, 7 patients (12%) were somewhat satisfied and needed one more fat grafting procedure to achieve complete satisfaction, and 2 patients (4%) were dissatisfied with the results. Three cases of temporary swelling of the hands resolved naturally. No long-term complications were seen. CONCLUSIONS: This study covers over a decade of practical experience in applying fat grafts to hands. The procedure is effective in reshaping and rejuvenating the hand as it shows long-lasting results after 1-year follow-up. PMID- 28989237 TI - Lipofilling effects after breast cancer surgery in post-radiation patients: an analysis of results and algorithm proposal. AB - BACKGROUND: Lipofilling or autologous fat transfer is an established technique in plastic surgery. Herein, we describe the lipofilling effects after implant-based breast reconstruction in post-radiation patients and propose an algorithm for indication of lipofilling. METHODS: Forty patients with a history of breast cancer were included in this retrospective analysis. Patients had undergone either breast conserving therapy or mastectomy. Twenty-six patients underwent additional radiation therapy. Patients were assessed using a post-radiation skin scoring classification. RESULTS: In total, 68 lipofilling procedures were analyzed. Scar release, skin softening, improved quality of life, and improvement of post-radiation findings are results of lipofilling with a closed filtration system. In all patients with post-surgical radiation, an improvement of tissue quality was observed. Staging revealed that lipofilling improved mean post radiation skin scores of 2.40 +/- 0.89 to 1.21 +/- 0.76 (p <= 0.000). There was no recurrence of breast cancer in our study patients. CONCLUSIONS: This study introduces an algorithm using lipofilling in reconstructive breast surgery and especially in post-radiation patients with low risks as well as very high acceptance in patients with various indications for this procedure. A regenerative aspect was also detectable in patients following radiation therapy and reconstruction. Lipofilling is a safe and effective procedure with a low incidence of minor complications. It is therefore a feasible method to resolve volume deficiencies and asymmetric results after oncologic breast surgery. Nevertheless, a prospective study has now been initiated focusing on the oncologic safety of lipofilling including ultrasound and radiological examinations to validate the findings of this initial study. Level of Evidence: Level IV, therapeutic study. PMID- 28989239 TI - Scarring of the C8-T1 roots with partial avulsion in situ in total obstetric brachial plexus palsy. AB - BACKGROUND: Primary exploration of the brachial plexus in infants with obstetric palsy may reveal scarring of the lower roots with evidence of partial avulsion-in situ. As we have been treating this lesion by neurolysis only, we aimed to investigate the recovery of hand function following such approach. METHODS: A series of 14 cases of total obstetric palsy with with evidence of partial avulsion-in-situ of the lower roots were included. All lesions were treated by neurolysis only (with no neurotization of the lower roots). Management of the injured upper roots was done by neurotization. Recovery was assessed as per our motor grading system. RESULTS: After a minimum follow-up of 4 years, hand functional recovery was considered good in 7 patients and excellent in the remaining 7 patients. CONCLUSIONS: We highlight the scarring of lower roots with evidence of partial avulsion-in situ in obstetric palsy. We also document that neurolysis is an acceptable approach to such lesions. Level of Evidence: Level IV, therapeutic study. PMID- 28989240 TI - Evidence-Based Practice in the social sciences? A scale of causality, interventions, and possibilities for scientific proof. AB - This article discusses Evidence-Based Practice (EBP) in the social sciences. After a brief outline of the discussion, the work of William Herbert Dray (1921 2009) is examined. Dray, partly following Collingwood, worked on different forms of causality and methodology in historical explanation (in comparison to the social sciences), based on a distinction between causes and reasons. Dray's ladder of rational understanding is also explored here. Taking his argumentation further and sometimes turning it upside-down, a scale of forms of causality is developed with accompanying types of interventions and possibilities for scientific proof of their effectivity. This scale makes it possible to weigh interventions regarding the degree to which "hard" scientific proof is possible for them. The article concludes with a brief discussion of how interventions in psychology and education should be chosen and can be justified, both those that do and those that don't lend themselves to empirical research. PMID- 28989241 TI - Rise Time Reduction of Thermal Actuators Operated in Air and Water through Optimized Pre-Shaped Open-Loop Driving. AB - Electrothermal actuators have many advantages compared to other actuators used in Micro-Electro-Mechanical Systems (MEMS). They are simple to design, easy to fabricate and provide large displacements at low voltages. Low voltages enable less stringent passivation requirements for operation in liquid. Despite these advantages, thermal actuation is typically limited to a few kHz bandwidth when using step inputs due to its intrinsic thermal time constant. However, the use of pre-shaped input signals offers a route for reducing the rise time of these actuators by orders of magnitude. We started with an electrothermally actuated cantilever having an initial 10-90% rise time of 85 MUs in air and 234 MUs in water for a standard open-loop step input. We experimentally characterized the linearity and frequency response of the cantilever when operated in air and water, allowing us to obtain transfer functions for the two cases. We used these transfer functions, along with functions describing desired reduced rise-time system responses, to numerically simulate the required input signals. Using these pre-shaped input signals, we improved the open-loop 10-90% rise time from 85 MUs to 3 MUs in air and from 234 MUs to 5 MUs in water, an improvement by a factor of 28 and 47, respectively. Using this simple control strategy for MEMS electrothermal actuators makes them an attractive alternative to other high speed micromechanical actuators such as piezoelectric stacks or electrostatic comb structures which are more complex to design, fabricate, or operate. PMID- 28989243 TI - A Comprehensive Review on Rasam: A South Indian Traditional Functional Food. AB - The view that food can have an expanded role that goes well beyond providing a source of nutrients truly applies to traditional functional foods. The systematic consumption of such traditional functional food provides an excellent preventive measure to ward off many diseases. Rasam, a soup of spices, is a traditional South Indian food. It is traditionally prepared using tamarind juice as a base, with the addition of Indian sesame oil, turmeric, tomato, chili pepper, pepper, garlic, cumin, curry leaves, mustard, coriander, asafoetida, sea salt, and water. Rasam is a classic example of traditional functional food with all its ingredients medicinally claimed for various ailments. The preclinical and clinical studies on rasam and its ingredients support their traditional claim. This review is an attempt to compile the literatures on rasam, its ingredients, and to highlight its medicinal potential that has been underestimated. PMID- 28989242 TI - Developing New Antimicrobial Therapies: Are Synergistic Combinations of Plant Extracts/Compounds with Conventional Antibiotics the Solution? AB - The discovery of penicillin nearly 90 years ago revolutionized the treatment of bacterial disease. Since that time, numerous other antibiotics have been discovered from bacteria and fungi, or developed by chemical synthesis and have become effective chemotherapeutic options. However, the misuse of antibiotics has lessened the efficacy of many commonly used antibiotics. The emergence of resistant strains of bacteria has seriously limited our ability to treat bacterial illness, and new antibiotics are desperately needed. Since the discovery of penicillin, most antibiotic development has focused on the discovery of new antibiotics derived from microbial sources, or on the synthesis of new compounds using existing antibiotic scaffolds to the detriment of other lines of discovery. Both of these methods have been fruitful. However, for a number of reasons discussed in this review, these strategies are unlikely to provide the same wealth of new antibiotics in the future. Indeed, the number of newly developed antibiotics has decreased dramatically in recent years. Instead, a reexamination of traditional medicines has become more common and has already provided several new antibiotics. Traditional medicine plants are likely to provide further new antibiotics in the future. However, the use of plant extracts or pure natural compounds in combination with conventional antibiotics may hold greater promise for rapidly providing affordable treatment options. Indeed, some combinational antibiotic therapies are already clinically available. This study reviews the recent literature on combinational antibiotic therapies to highlight their potential and to guide future research in this field. PMID- 28989246 TI - General Overview of Phenolics from Plant to Laboratory, Good Antibacterials or Not. AB - The emergence and rapid development of seriously drug-resistant pathogens have created the greatest danger to public health and made the treatment of infectious diseases ineffective; to control the antibiotic-resistant microbes, the discovery of new effective antibacterials with new mechanisms of action against bacteria remains an urgent task to control the bacterial resistance. The paucity of infections in wild plants supports the role of innate defense system of plants. Many researchers nominate the natural extracts to act against bacterial resistance mechanisms, and the majority of them have now been focused on the combination of plant extracts and antibiotics to define the availability of resistance modification agents. Only very few numbers of natural products are successful to reach experiments circle beyond the in vitro assays. Phenols and phenolic acids could serve as good candidates to the natural antibacterial arsenal. The pyrogallol-based compounds are more potent than others such as catechol or resorcinol, gallic acid, and the hydroxycinnamic acid (ferulic acid) are destructing the bacterial cell wall of Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, leading to leakage of cellular contents. These compounds have stronger activity against Gram-positive microorganisms, and some of them showed good synergism with antibiotics, for example, pentagalloylglucopyranose, is shown a synergism with penicillin G against methicillin-resistant S. aureus, another example is the interesting synergism between epicatechin gallate and oxacillin where the minimal inhibitory concentrations of oxacillin reduced around 500 times by the addition of epicatechin gallate to the antibiotic. PMID- 28989245 TI - Plants' Natural Products as Alternative Promising Anti-Candida Drugs. AB - Candida is a serious life-threatening pathogen, particularly with immunocompromised patients. Candida infections are considered as a major cause of morbidity and mortality in a broad range of immunocompromised patients. Candida infections are common in hospitalized patients and elderly people. The difficulty to eradicate Candida infections is owing to its unique switch between yeast and hyphae forms and more likely to biofilm formations that render resistance to antifungal therapy. Plants are known sources of natural medicines. Several plants show significant anti-Candida activities and some of them have lower minimum inhibitory concentration, making them promising candidates for anti-Candida therapy. However, none of these plant products is marketed for anti-Candida therapy because of lack of sufficient information about their efficacy, toxicity, and kinetics. This review revises major plants that have been tested for anti Candida activities with recommendations for further use of some of these plants for more investigation and in vivo testing including the use of nanostructure lipid system. PMID- 28989248 TI - Potential Antitumor Effects of Pomegranates and Its Ingredients. AB - The treatment based on plant or plant derivatives is a promising strategy in the killing of cancers cells. Moreover, wide-ranging finding has established that medicinal plant and its ingredient modulate several cells signaling pathways or inhibiting the carcinogenesis process. In this vista, pomegranates fruits, seeds and peels illustrate cancer preventive role seems to be due to rich source of antioxidant and other valuable ingredients. Furthermore, anti-tumour activities of pomegranates have been evidences through the modulation of cell signaling pathways including transcription factor, apoptosis and angiogenesis. In this review article, anti-tumor activity of pomegranates and its components or its different type of extracts are described to understand the mechanism of action of pomegranates in cancer therapy. PMID- 28989247 TI - Targeting Mitochondrial Dysfunction for the Treatment of Diabetic Complications: Pharmacological Interventions through Natural Products. AB - Diabetes mellitus is a chronic hyperglycemic condition with deleterious effects on microcirculation, resulting in diabetic complications. Chronic hyperglycemia induces the generation of reactive oxygen species (ROS), which are the key pathological triggers in the development of diabetic complications. ROS are responsible for the activation of various pathways involved in the genesis of diabetic complications, mitochondrial dysfunction, as well as insulin resistance. The review describes normal mitochondrial physiology and abnormal alterations, which occur in response to hyperglycemia. Mitochondrial biogenesis is a highly regulated process mediated by several transcription factors, wherein mitochondrial fusion and fission occur in harmony in a normal healthy cell. However, this harmony is disrupted in hyperglycemic condition indicated by alteration in functions of essential transcription factors. Hyperglycemia-induced mitochondrial dysfunction plays a key role in diabetic complications, pancreatic beta-cell dysfunction, as well as skeletal muscle insulin resistance as demonstrated by various in vitro, preclinical, and clinical studies. The review focuses on the various factors involved in mitochondrial biogenesis and maintenance of healthy mitochondrial function. Several phytoconstituents act through these pathways, either directly by stimulating biogenesis or indirectly by inhibiting or preventing dysfunction, and produce a beneficial effect on overall mitochondrial function. These phytoconstituents have enormous potential in amelioration of diabetic complications by restoring normal mitochondrial physiology and need detailed evaluation by preclinical and clinical studies. Such phytoconstituents can be included as nutraceuticals or adjuvant therapy to the mainstream treatment of diabetes. PMID- 28989244 TI - Herbal Drugs from Sudan: Traditional Uses and Phytoconstituents. AB - Sudan folklore medicine is characterized by a unique combination of Islamic, Arabic, and African cultures. In poor communities, traditional medicine has remained as the most reasonable source of treatment of several diseases and microbial infections. Although the traditional medicine is accepted in Sudan, to date there is no updated review available, which focuses on most effective and frequently used Sudanese medicinal plants. Thus, this review aims to summarize the published information on the ethnobotanical uses of medicinal plants from Sudan, preparation methods, phytochemistry, and ethnopharmacology. The collected data demonstrate that Sudanese medicinal plants have been reported to possess a wide range of traditional medicinal uses including different microbial infections, gastrointestinal disorders, malaria, diabetes, rheumatic pain, respiratory system disorders, jaundice, urinary system inflammations, wounds, cancer, and different microbial infections. In most cases, the pharmacological studies were in agreement with traditional uses. Moreover, several bioactive compounds such as flavonoids, saponins, alkaloids, steroids, terpenes, tannins, fatty acids, and essential oils have been identified as active constituents. Although this review demonstrates the importance of ethnomedicine medicines in the treatment of several diseases in Sudan, further researches to validate the therapeutic uses and safety of these plants through phytochemical screening, different biological activity assays, and toxicological studies are still needed. PMID- 28989249 TI - Review of Holarrhena antidysenterica (L.) Wall. ex A. DC.: Pharmacognostic, Pharmacological, and Toxicological Perspective. AB - Holarrhena antidysenterica (L.) Wall. ex A. DC. is a medicinal plant abundantly found in India. Its uses are mentioned in the classical Ayurvedic literature and by many folklore claims. The plant is also of extreme economic importance. Its seeds are mainly used as an antidiabetic remedy. All pharmacological and toxicological aspects of this plant are discussed in this review. PMID- 28989251 TI - A Hidden Treasure: The Borneo Mistletoes. AB - The European mistletoe, Viscum album, is the most common consumed adjuvant among cancer patients in Europe. Its success warrants a report on three most apparent mistletoes found in Borneo Island, namely Scurrula ferruginea, Macrosolen cochinchinensis, and Dendrophthoe curvata. The traditional and pharmacological uses of these mistletoes include antibacterial, anticancer, antiviral, antihypertensive, antioxidative, and cytotoxic effects. Phytochemicals such as flavonols, alkaloids, tannins, and gallic acid have been reported in one of these mistletoes. This review discusses the potential of these mistletoes as therapeutic agents. PMID- 28989250 TI - A Review Study on Phytochemistry and Pharmacology Applications of Juglans Regia Plant. AB - In recent years, the use of medicinal plants increased considerably; so that today, the use of traditional medicine, as well as medicinal plants is necessary for the aim of producing more effective drugs with fewer side effects and determining the effective doses. With the scientific name of Juglans regia, walnut plant is a medicinal plant with different properties that is considered less, despite having great therapeutic potential in the traditional medicine. The aim of this study was to review the dispersal of walnut plants, the chemical compounds, and therapeutic effects of walnuts on antioxidant activity, antidiabetic, hypolipidemic, antimicrobial, and antihypertensive activities, as well as liver protection. Data of this review study have been collected from the books and scientific articles published in databases such as Science Direct, Web of Science, Scopus, PubMed, and Scientific Information Database. While this plant having high antioxidant capabilities, walnuts are composed of many chemical compounds such as ascorbic acid, flavonoids, quercetin, and caffeic acid. Experimental studies have shown that walnuts reduced blood glucose and lipids and also decreased blood pressure. They have antioxidant, antidiabetic, antimicrobial, and liver-protective properties. The use of walnuts in traditional medicine and review of experimental studies demonstrated the presence of multiple, effective, and useful compounds which may provide the opportunity for the production of lipid-lowering, antidiabetes, and liver protective drugs. Due to the effects of walnuts on improving the complications of various diseases, the need for doing comprehensive clinical trials for the use of walnuts in the treatment of diseases is necessary. PMID- 28989252 TI - Operculina turpethum (Linn.) Silva Manso as a Medicinal Plant Species: A Review on Bioactive Components and Pharmacological Properties. AB - Operculina turpethum (Linn.) (OT) Silva Manso belongs to the family Convolvulaceae. This review incorporates literature for the phytochemical and pharmacological profile of OT herb. Exhaustive literature survey was done using all the details on phytochemistry and pharmacology of OT available. This herb was found to be a potent source of bioactive compounds such as alpha- and beta turpethein, turpethinic acids (A, B, C, D, and E), coumarins, cycloartenol, lanosta-5-ene, 24-methylene-delta-5-lanosterol, alpha- and beta-rhamnose, beta sitosterol, lupeol, scopoletin, betulin, acrylamide, stigma-5,22dien-3-O-beta-D glucopyranoside, beta-sitosterol-beta-D-glucoside (H-1), 22,23-dihydro-alpha spinosterol-beta-D-glucoside (H-2), and salicylic acid (CH-2), which are useful in fevers, edema, ascites, anorexia, constipation, hepatosplenomegaly, hemorrhoids, cervical lymphadenitis, fistulas, constipation, chronic gout, fever, bronchitis, ulcers, hemorrhoids, tumors, obesity, jaundice, herpes, induce lacrimation, and other skin disorders. From the aerial parts of OT, four new dammarane-type saponins that are operculinosides A-D (1-4) were isolated that showed particular hepatoprotective activities. All the compounds are reported to possess pharmacological properties such as antibacterial, anti-inflammatory, analgesic, hepatoprotective, anti-arthritic, ulcer protective, antidiarrheal, antidiabetic, and cytotoxic properties. PMID- 28989254 TI - Superconvergence of the local discontinuous Galerkin method for nonlinear convection-diffusion problems. AB - In this paper, we discuss the superconvergence of the local discontinuous Galerkin methods for nonlinear convection-diffusion equations. We prove that the numerical solution is [Formula: see text]th-order superconvergent to a particular projection of the exact solution, when the upwind flux and the alternating fluxes are used. The proof is valid for arbitrary nonuniform regular meshes and for piecewise polynomials of degree k ([Formula: see text]). The numerical experiments reveal that the property of superconvergence actually holds true for general fluxes. PMID- 28989255 TI - Modified forward-backward splitting midpoint method with superposition perturbations for the sum of two kinds of infinite accretive mappings and its applications. AB - In a real uniformly convex and p-uniformly smooth Banach space, a modified forward-backward splitting iterative algorithm is presented, where the computational errors and the superposition of perturbed operators are considered. The iterative sequence is proved to be convergent strongly to zero point of the sum of infinite m-accretive mappings and infinite [Formula: see text]-inversely strongly accretive mappings, which is also the unique solution of one kind variational inequalities. Some new proof techniques can be found, especially, a new inequality is employed compared to some of the recent work. Moreover, the applications of the newly obtained iterative algorithm to integro-differential systems and convex minimization problems are exemplified. PMID- 28989253 TI - Psidium guajava: A Single Plant for Multiple Health Problems of Rural Indian Population. AB - The rural population in India faces a number of health problems and often has to rely on local remedies. Psidium guajava Linn. (guava), a tropical plant which is used as food and medicine can be used by rural communities due to its several medicinal properties. A literature search was undertaken to gauge the rural health scenario in India and compile the available literature on guava so as to reflect its usage in the treatment of multiple health conditions prevalent in rural communities. Towards this, electronic databases such as Pubmed, Science Direct, google scholar were scanned. Information on clinical trials on guava was obtained from Cochrane Central Register of Controlled Trials and Clinicaltrial.gov. The literature survey revealed that guava possesses various medicinal properties which have been reported from across the globe in the form of ethnobotanical/ethnopharmacological surveys, laboratory investigations and clinical trials. Besides documenting the safety of guava, the available literature shows that guava is efficacious against the following conditions which rural communities would encounter. (a) Gastrointestinal infections; (b) Malaria; (c)Respiratory infections; (d) Oral/dental infections; (e) Skin infections; (f) Diabetes; (g) Cardiovascular/hypertension; (h) Cancer; (i) Malnutrition; (j) Women problems; (k) Pain; (l) Fever; (m) Liver problems; (n) Kidney problems. In addition, guava can also be useful for treatment of animals and explored for its commercial applications. In conclusion, popularization of guava, can have multiple applications for rural communities. PMID- 28989257 TI - Fibonacci statistical convergence and Korovkin type approximation theorems. AB - The purpose of this paper is twofold. First, the definition of new statistical convergence with Fibonacci sequence is given and some fundamental properties of statistical convergence are examined. Second, we provide various approximation results concerning the classical Korovkin theorem via Fibonacci type statistical convergence. PMID- 28989256 TI - Boundedness of Marcinkiewicz integrals with rough kernels on Musielak-Orlicz Hardy spaces. AB - Let [Formula: see text] satisfy that [Formula: see text], for any given [Formula: see text], is an Orlicz function and [Formula: see text] is a Muckenhoupt [Formula: see text] weight uniformly in [Formula: see text]. The Musielak-Orlicz Hardy space [Formula: see text] is defined to be the set of all tempered distributions such that their grand maximal functions belong to the Musielak Orlicz space [Formula: see text]. In this paper, the authors establish the boundedness of Marcinkiewicz integral [Formula: see text] from [Formula: see text] to [Formula: see text] under weaker smoothness conditions assumed on Omega. This result is also new even when [Formula: see text] for all [Formula: see text], where phi is an Orlicz function. PMID- 28989258 TI - The closure property of [Formula: see text]-tensors under the Hadamard product. AB - In this paper, we investigate the closure property of [Formula: see text]-tensors under the Hadamard product. It is shown that the Hadamard products of Hadamard powers of strong [Formula: see text]-tensors are still strong [Formula: see text] tensors. We then bound the minimal real eigenvalues of the comparison tensors of the Hadamard products involving strong [Formula: see text]-tensors. Finally, we show how to attain the bounds by characterizing these [Formula: see text] tensors. PMID- 28989259 TI - Weak convergence to isotropic complex [Formula: see text] random measure. AB - In this paper, we prove that an isotropic complex symmetric alpha-stable random measure ([Formula: see text]) can be approximated by a complex process constructed by integrals based on the Poisson process with random intensity. PMID- 28989260 TI - Quantitative unique continuation for the linear coupled heat equations. AB - In this paper, we established a quantitative unique continuation results for a coupled heat equations, with the homogeneous Dirichlet boundary condition, on a bounded convex domain Omega of [Formula: see text] with smooth boundary ?Omega. Our result shows that the value of the solutions can be determined uniquely by its value on an arbitrary open subset omega of Omega at any given positive time T. PMID- 28989261 TI - A family of conjugate gradient methods for large-scale nonlinear equations. AB - In this paper, we present a family of conjugate gradient projection methods for solving large-scale nonlinear equations. At each iteration, it needs low storage and the subproblem can be easily solved. Compared with the existing solution methods for solving the problem, its global convergence is established without the restriction of the Lipschitz continuity on the underlying mapping. Preliminary numerical results are reported to show the efficiency of the proposed method. PMID- 28989262 TI - On a new generalized symmetric vector equilibrium problem. AB - In this paper, a new form of the symmetric vector equilibrium problem is introduced and, by mixing properties of the nonlinear scalarization mapping and the maximal element lemma, an existence theorem for it is established. We show that Ky Fan's lemma, as a usual technique for proving the existence results for equilibrium problems, implies the maximal element lemma, while it is useless for proving the main theorem of this paper. Our results can be viewed as an extension and improvement of the main results obtained by Farajzadeh (Filomat 29(9):2097 2105, 2015) and some corresponding results that appeared in this area by relaxing the lower semicontinuity, quasiconvexity on the mappings and being nontrivial of the dual cones. Finally, some examples are given to support the main results. PMID- 28989263 TI - Modeling and characterization of shape memory alloy springs with water cooling strategy in a neurosurgical robot. AB - Since shape memory alloy (SMA) has high power density and is magnetic resonance imaging (MRI) compatible, it has been chosen as the actuator for the meso-scale minimally invasive neurosurgical intracranial robot (MINIR-II) that is envisioned to be operated under continuous MRI guidance. We have devised a water cooling strategy to improve its actuation frequency by threading a silicone tube through the spring coils to form a compact cooling module-integrated actuator. To create active bi-directional motion in each robot joint, we configured the SMA springs in an antagonistic way. We modeled the antagonistic SMA spring behavior and provided the detailed steps to simulate its motion for a complete cycle. We investigated heat transfer during the resistive heating and water cooling processes. Characterization experiments were performed to determine the parameters used in both models, which were then verified by comparing the experimental and simulated data. The actuation frequency of the antagonistic SMAs was evaluated for several motion amplitudes and we could achieve a maximum actuation frequency of 0.143 Hz for a sinusoidal trajectory with 2 mm amplitude. Lastly, we developed a robotic system to implement the actuators on the MINIR-II to move its end segment back and forth for approximately +/-25 degrees . PMID- 28989264 TI - Killer Apps: Developing Novel Applications That Enhance Team Coordination, Communication, and Effectiveness. AB - As part of the Lorentz workshop, "Interdisciplinary Insights into Group and Team Dynamics," held in Leiden, Netherlands, this article describes how Geeks and Groupies (computer and social scientists) may benefit from interdisciplinary collaboration toward the development of killer apps in team contexts that are meaningful and challenging for both. First, we discuss interaction processes during team meetings as a research topic for both Groupies and Geeks. Second, we highlight teamwork in health care settings as an interdisciplinary research challenge. Third, we discuss how an automated solution for optimal team design could benefit team effectiveness and feed into team-based interventions. Fourth, we discuss team collaboration in massive open online courses as a challenge for both Geeks and Groupies. We argue for the necessary integration of social and computational research insights and approaches. In the hope of inspiring future interdisciplinary collaborations, we develop criteria for evaluating killer apps including the four proposed here-and discuss future research challenges and opportunities that potentially derive from these developments. PMID- 28989265 TI - Technical Considerations in Revision Anterior Cruciate Ligament (ACL) Reconstruction for Operative Techniques in Orthopaedics. AB - As the incidence of anterior cruciate ligament (ACL) reconstruction continues to increase, the rate of revision surgery continues to climb. Revision surgery has inherent challenges that must be addressed in order to achieve successful results. The cause of the primary ACL reconstruction failure should be determined, and careful preoperative planning should be performed to address the cause(s) of failure. Each patient undergoing revision surgery should undergo a thorough history and physical examination, receive full length alignment radiographs, lateral radiographs, 45-degree flexion weight-bearing postero anterior radiographs, and patellofemoral radiographs. 3-dimensional computed topography (CT) scan should be performed to assess tunnel position and widening. Magnetic resonance imaging (MRI) should be used to assess for intra-articular soft tissue pathology. Meniscal tears, meniscal deficiency, anterolateral capsule injuries, bony morphology, age, activity level, connective tissue diseases, infection, graft choice, and tunnel position can all impact the success of ACL reconstruction surgery. Meniscal lesions should be repaired, and in cases of persistent rotatory instability, extra-articular procedures may be indicated. Furthermore, osteotomies may be needed to correct malalignment or excess posterior tibial slope. Depending on the placement and condition of the original femoral and tibial tunnels, revision surgery may be performed in a single procedure or in a staged manner. In most cases, the surgery can be performed in one procedure. Regardless, the surgeon must communicate with the patient openly regarding the implications of revision ACL surgery and the treatment plan should be developed in a shared fashion between the surgeon and the patient. PMID- 28989266 TI - Measuring Anxiety in Children: The Importance of Separate Mother and Father Reports. AB - BACKGROUND: Previous research suggests that it is important to use parental reports when assessing children's anxiety, but it remains unclear to what extent there are differences between mothers' and fathers' scores and whether these potential differences have any repercussions for the psychometric properties of the scale being used. OBJECTIVE: This study was conducted to investigate parental differences on the Parent version of the Screen for Child Anxiety Related Emotional Disorders-Revised (SCARED-RP), a rating scale for measuring child anxiety symptoms. The second aim was to re-examine the reliability and validity of the SCARED-RP, in light of these possible differences. METHODS: The SCARED-RP and the Child Behaviour Checklist (CBCL) were administered to parents of clinically anxious children (n = 81), and control children (n = 108). All children (n = 189) completed the SCARED-R. RESULTS: Significant correlations between mother and father reports were found within the clinically anxious sample. Mothers showed significantly more correspondence with their children in the control group than fathers. The SCARED-RP internal consistency on total scale was excellent (mothers: .94; fathers: .94) and moderate to good for all subscales (from .66 Situational-Environmental Phobia to .93 Animal Phobia). The SCARED-RP differentiated well between clinically anxious and control children (mother and father data). The concurrent validity was supported by strong correlations with the CBCL anxious-depressed scale. CONCLUSION: Differences between mother and father reports suggest the importance of obtaining information from both parents separately. Furthermore, the SCARED-RP is a useful instrument for assessing children's anxiety disorder symptoms in clinical and research settings. PMID- 28989267 TI - The Impact of Transcription Writing Interventions for First-Grade Students. AB - We examined the effects of transcription instruction for students in first grade. Students in the lowest 70% of the participating schools were selected for the study. These 81 students were randomly assigned to: (a) spelling instruction, (b) handwriting instruction, (c) combination spelling and handwriting instruction, or (d) no intervention. Intervention was provided in small groups of 4 students, 25 min a day, 4 days a week for 8 weeks. Students in the spelling condition outperformed the control group on spelling measures with moderate effect sizes noted on curriculum-based writing measures (e.g., correct word sequence; g range = 0.34 to 0.68). Students in the handwriting condition outperformed the control group on correct word sequences with small to moderate effects on other handwriting and writing measures (g range = 0.31 to 0.71). Students in the combined condition outperformed the control group on correct word sequences with a small effect on total words written (g range = 0.39 to 0.84). PMID- 28989269 TI - Electrochemistry of a Robust Neural Interface. PMID- 28989268 TI - Parental Accommodation Predicts Symptom Severity at Long-term Follow-Up in Children with Obsessive-Compulsive Disorder. AB - Pediatric obsessive-compulsive disorder (OCD) is a chronic condition affecting millions of children. Though well intentioned, accommodation (i.e., a parent's attempt to assuage their child's distress and anxiety) is thought to increase OCD symptom severity and may cause greater OCD-related impairment. The present study sought to examine the relative contribution of parental accommodation in predicting OCD symptom severity. Children between the ages of 6 and 18 (and their parents) participated in a prospective, longitudinal study investigating the course of pediatric OCD utilizing a longitudinal design. Data was collected at intake (n = 30) and two-years (n = 22) post-intake controlling for age, anxiety and depression. Parental accommodation (measured at intake) significantly predicted OCD symptom severity and was the strongest predictor at both intake and two-year follow-up. These preliminary findings highlight the importance of further research seeking to delineate factors relevant to the development and maintenance of accommodation as well as parent-level variables that might mediate the relationship between accommodation and OCD symptom severity. PMID- 28989270 TI - Robust Visualization and Discrimination of Nanoparticles by Interferometric Imaging. AB - Single-molecule and single-nanoparticle biosensors are a growing frontier in diagnostics. Digital biosensors are those which enumerate all specifically immobilized biomolecules or biological nanoparticles, and thereby achieve limits of detection usually beyond the reach of ensemble measurements. Here we review modern optical techniques for single nanoparticle detection and describe the single-particle interferometric reflectance imaging sensor (SP-IRIS). We present challenges associated with reliably detecting faint nanoparticles with SP-IRIS, and describe image acquisition processes and software modifications to address them. Specifically, we describe a image acquisition processing method for the discrimination and accurate counting of nanoparticles that greatly reduces both the number of false positives and false negatives. These engineering improvements are critical steps in the translation of SP-IRIS towards applications in medical diagnostics. PMID- 28989271 TI - The Causal Effect of Bus Rapid Transit on Changes in Transit Ridership. AB - Numerous studies have reported ridership increases along routes when Bus rapid transit (BRT) replaces conventional bus service, but these increases could be due simply to broader temporal trends in transit ridership. To address this limitation, we compared changes in ridership among routes where BRT was implemented to routes where BRT was planned or already existed in King County, Washington. Ridership was measured at 2010, 2013, and 2014. Ridership increased by 35% along routes where BRT was implemented from 2010 to 2013 compared to routes that maintained conventional bus service. Ridership increased by 29% along routes where BRT was implemented from 2013 to 2014 compared to consistent existing BRT service. These results provide stronger evidence for a causal relationship between BRT and increased transit ridership and a more accurate estimate of the independent effect of BRT on ridership. PMID- 28989272 TI - Design and Fabrication of MR-Tracked Metallic Stylet for Gynecologic Brachytherapy. AB - Active magnetic resonance (MR) tracking for gynecologic brachytherapy was made possible by attaching the micro radiofrequency coils to the brachytherapy applicator. The rectangular planar micro coil was fabricated using flexible printed circuits with dimensions of 8mm*1.5mm. A 5-Fr (1.6mm) tungsten brachytherapy stylet was custom-machined to incorporate the micro coils. The finite element analysis and the phantom tissue studies show that the proposed device enables in situ, real-time guidance of access routes to the target anatomy safely and accurately. The setup was tested in a Siemens 3T MR scanner. The micro coils can be localized rapidly (up to 40 Hz) and precisely (resolution: 0.6*0.6*0.6mm3) using an MR-tracking sequence. PMID- 28989273 TI - Mechanical Model of Dexterous Continuum Manipulators with Compliant Joints and Tendon/External Force Interactions. AB - Dexterous continuum manipulators (DCMs) have been widely adopted for minimally- and less-invasive surgery. During the operation, these DCMs interact with surrounding anatomy actively or passively. The interaction force will inevitably affect the tip position and shape of DCMs, leading to potentially inaccurate control near critical anatomy. In this paper, we demonstrated a 2D mechanical model for a tendon actuated, notched DCM with compliant joints. The model predicted deformation of the DCM accurately in the presence of tendon force, friction force, and external force. A partition approach was proposed to describe the DCM as a series of interconnected rigid and flexible links. Beam mechanics, taking into consideration tendon interaction and external force on the tip and the body, was applied to obtain the deformation of each flexible link of the DCM. The model results were compared with experiments for free bending as well as bending in the presence of external forces acting at either the tip or body of the DCM. The overall mean error of tip position between model predictions and all of the experimental results was 0.62+/-0.41mm. The results suggest that the proposed model can effectively predict the shape of the DCM. PMID- 28989274 TI - Factors Associated With Negative Attitudes Toward Speaking in Preschool-Age Children Who Do and Do Not Stutter. AB - PURPOSE: This study explored relations between the negativity of children's speech-related attitudes as measured by the Communication Attitude Test for Preschool and Kindergarten Children Who Stutter (KiddyCAT; Vanryckeghem & Brutten, 2007) and (a) age; (b) caregiver reports of stuttering and its social consequences; (c) types of disfluencies; and (d) standardized speech, vocabulary, and language scores. METHOD: Participants were 46 preschool-age children who stutter (CWS; 12 females, 34 males) and 66 preschool-age children who do not stutter (CWNS; 35 females, 31 males). After a conversation, children completed standardized tests and the KiddyCAT while their caregivers completed scales on observed stuttering behaviors and their consequences. RESULTS: The KiddyCAT scores of both the CWS and the CWNS were significantly negatively correlated with age. Both groups' KiddyCAT scores increased with higher scores on the Speech Fluency Rating Scale of the Test of Childhood Stuttering (Gillam, Logan, & Pearson, 2009). Repetitions were a significant contributor to the CWNS's KiddyCAT scores, but no specific disfluency significantly contributed to the CWS's KiddyCAT scores. Greater articulation errors were associated with higher KiddyCAT scores in the CWNS. No standardized test scores were associated with KiddyCAT scores in the CWS. CONCLUSION: Attitudes that speech is difficult are not associated with similar aspects of communication for CWS and CWNS. Age significantly contributed to negative speech attitudes for CWS, whereas age, repetitions, and articulation errors contributed to negative speech attitudes for CWNS. PMID- 28989275 TI - Audit Culture: Unintended Consequences of Accountability Practices in Evidence Based Programs. AB - Evaluation has become expected within the nonprofit sector, including HIV prevention service delivery through community-based organizations (CBOs). While staff and directors at CBOs may acknowledge the potential contribution of evaluation data to the improvement of agency services, the results of evaluation are often used to demonstrate fiscal prudence, efficiency, and accountability to funders and the public, rather than to produce information for the organization's benefit. We conducted 22 in-depth, semistructured interviews with service providers from four agencies implementing the same evidence-based HIV prevention intervention. We use the lens of "audit culture" to understand how the evaluation and accountability mandates of evidence-based program implementation within HIV prevention service provision affect provider-client relations, staff members' daily work, and organizational focus in natural settings, or contexts without continuous support and implementation monitoring. We conclude with recommendations for improving the use and methods of evaluation within HIV prevention service delivery. PMID- 28989276 TI - Stability of medicines after repackaging into multicompartment compliance aids: eight criteria for detection of visual alteration. AB - INTRODUCTION: Multicompartment compliance aids (MCA) are widely used by patients. They support the management of medication and reduce unintentional nonadherence. MCA are filled with medicines unpacked from their original packaging. Swiss pharmacists currently provide MCA for 1-2 weeks, although little and controversial information exists on the stability of repackaged medicines. OBJECTIVE: We aimed to validate the usefulness of a simple screening method capable of detecting visual stability problems with repackaged medicines. METHODS: We selected eight criteria for solid formulations from The International Pharmacopoeia: (1) rough surface, (2) chipping, (3) cracking, (4) capping, (5) mottling, (6) discoloration, (7) swelling, and (8) crushing. A selection of 24 critical medicines was repackaged in three different MCA (Pharmis(r), SureMedTM, and self-produced blister) and stored at room temperature for 4 weeks. Pharmis(r) was additionally stored at accelerated conditions. Appearance was scored weekly. RESULTS: Six alterations (rough surface, cracking, mottling, discoloration, swelling, and crushing) were observed at accelerated conditions. No alteration was observed at room temperature, except for the chipping of tablets that had been stuck to cold seal glue. CONCLUSION: The eight criteria can detect alterations of the appearance of oral solid medicines repackaged in MCA. In the absence of specific guidelines, they can serve as a simple screening method in community pharmacies for identifying medicines unsuitable for repackaging. PMID- 28989277 TI - A Metagenomic Analysis of Bacterial Microbiota in the Digestive Tract of Triatomines. AB - The digestive tract of triatomines (DTT) is an ecological niche favored by microbiota whose enzymatic profile is adapted to the specific substrate availability in this medium. This report describes the molecular enzymatic properties that promote bacterial prominence in the DTT. The microbiota composition was assessed previously based on 16S ribosomal DNA, and whole sequenced genomes of bacteria from the same genera were used to calculate the GC level of rare and prominent bacterial species in the DTT. The enzymatic reactions encoded by coding sequences of both rare and common bacterial species were then compared and revealed key functions explaining why some genera outcompete others in the DTT. Representativeness of DTT microbiota was investigated by shotgun sequencing of DNA extracted from bacteria grown in liquid Luria-Bertani broth (LB) medium. Results showed that GC-rich bacteria outcompete GC-poor bacteria and are the dominant components of the DTT microbiota. In addition, oxidoreductases are the main enzymatic components of these bacteria. In particular, nitrate reductases (anaerobic respiration), oxygenases (catabolism of complex substrates), acetate-CoA ligase (tricarboxylic acid cycle and energy metabolism), and kinase (signaling pathway) were the major enzymatic determinants present together with a large group of minor enzymes including hydrogenases involved in energy and amino acid metabolism. In conclusion, despite their slower growth in liquid LB medium, bacteria from GC-rich genera outcompete the GC-poor bacteria because their specific enzymatic abilities impart a selective advantage in the DTT. PMID- 28989278 TI - Whole-body electromyostimulation and protein supplementation favorably affect sarcopenic obesity in community-dwelling older men at risk: the randomized controlled FranSO study. AB - BACKGROUND: Sarcopenic obesity (SO) is a geriatric syndrome characterized by the disproportion between the amount of lean mass and fat mass. Exercise decreases fat and maintains muscle mass; however, older people fail to exercise at doses sufficient to affect musculoskeletal and cardiometabolic risk factors. The aim of this study was to evaluate the effect of whole-body electromyostimulation (WB EMS), a time-efficient, joint-friendly and highly individualized exercise technology, on sarcopenia and SO in older men. MATERIALS AND METHODS: A total of 100 community-dwelling northern Bavarian men aged >=70 years with sarcopenia and obesity were randomly (1-1-1) assigned to either 16 weeks of 1) WB-EMS and protein supplementation (WB-EMS&P), 2) isolated protein supplementation or 3) nonintervention control. WB-EMS consisted of 1.5*20 min (85 Hz, 350 us, 4 s of strain to 4 s of rest) applied with moderate-to-high intensity while moving. We further generated a daily protein intake of 1.7-1.8 g/kg/body mass per day. The primary study end point was Sarcopenia Z-Score, and the secondary study end points were body fat rate (%), skeletal muscle mass index (SMI) and handgrip strength. RESULTS: Intention-to-treat analysis determined a significantly favorable effect of WB-EMS&P (P<0.001) and protein (P=0.007) vs control. Both groups significantly (P<0.001) lost body fat (WB-EMS&P: 2.1%; protein: 1.1%) and differed significantly (P<=0.004) from control (0.3%). Differences between WB EMS&P and protein were significant for the Sarcopenia Z-Score (P=0.39) and borderline nonsignificant (P=0.051) for body fat. SMI increased significantly in both groups (P<0.001 and P=0.043) and decreased significantly in the control group (CG; P=0.033); differences between the verum groups and control were significant (P<=0.009). Handgrip strength increased in the WB-EMS group (1.90 kg; P<0.001; P=0.050 vs control) only. No adverse effects of WB-EMS or protein supplementation were recorded. CONCLUSION: WB-EMS&P is a safe and efficient method for tackling sarcopenia and SO in older men. However, the suboptimum effect on functional parameters should be addressed by increased voluntary activation during WB-EMS application. PMID- 28989279 TI - Estimating the effectiveness of pulmonary rehabilitation for COPD exacerbations: reduction of hospital inpatient days during the following year. AB - AIMS: To study the short- and long-term results of pulmonary rehabilitation (PR) given in the Helsinki University Heart and Lung Center and to understand the hospital resources used to treat severe COPD exacerbations in the city of Helsinki. MATERIALS AND METHODS: Seventy-eight inactive patients with severe COPD were recruited for a PR course; three of them did not finish the course. The course took 6-8 weeks and included 11-16 supervised exercise sessions. Using electronic medical records, we studied all COPD patients with hospital admission in the city of Helsinki in 2014, including COPD diagnosis, criteria for exacerbation, and potential exclusion/inclusion criteria for PR. RESULTS: Seventy five of the patients finished the PR course and 92% of those patients showed clinically significant improvement. Their hospital days were reduced by 54% when compared to the year before. At 1 year after the course, 53% of the patients reported that they have continued with regular exercise training. In the city of Helsinki, 437 COPD patients were treated in a hospital due to exacerbation during 2014. On the basis of their electronic medical records, 57% of them would be suitable for PR. According to a rough estimate, 10%-20% hospital days could be saved annually if PR was available to all, assuming that the PR results would be as good as those shown here. CONCLUSIONS: The study showed that in a real-world setting, PR is efficient when measured by saved hospital days in severe COPD. Half of the patients could be motivated to continue exercising on their own. PMID- 28989280 TI - Exon Mapping in Long Noncoding RNAs Using Digital Filters. AB - Long noncoding RNAs (lncRNAs) which were initially dismissed as "transcriptional noise" have become a vital area of study after their roles in biological regulation were discovered. Long noncoding RNAs have been implicated in various developmental processes and diseases. Here, we perform exon mapping of human lncRNA sequences (taken from National Center for Biotechnology Information GenBank) using digital filters. Antinotch digital filters are used to map out the exons of the lncRNA sequences analyzed. The period 3 property which is an established indicator for locating exons in genes is used here. Discrete wavelet transform filter bank is used to fine-tune the exon plots by selectively removing the spectral noise. The exon locations conform to the ranges specified in GenBank. In addition to exon prediction, G-C concentrations of lncRNA sequences are found, and the sequences are searched for START and STOP codons as these are indicators of coding potential. PMID- 28989281 TI - Efficacy and tolerability of liposomal polyvinylpyrrolidone-iodine hydrogel for the localized treatment of chronic infective, inflammatory, dermatoses: an uncontrolled pilot study. AB - Infection is common in many chronic, inflammatory skin conditions but is often difficult to treat, in part due to growing bacterial resistance to antibiotics. Liposomal polyvinyl-pyrrolidone (PVP)-iodine hydrogel has a unique mode of action, combining the antiseptic and anti-inflammatory actions of PVP-iodine with the drug delivery and moisturizing properties of liposomes. We investigated the utility of liposomal PVP-iodine to treat infective dermatoses. In this prospective, single-arm (uncontrolled), open-label Phase II pilot study, patients with acne vulgaris (n=30), atopic dermatitis (n=20), impetigo contagiosa (n=10), and rosacea (n=10) received PVP-iodine (3%) hydrogel for <=4 weeks. Global Clinical Severity score improved for all dermatoses (range: 0.5 for acne vulgaris [p<0.001] to 1.0 for impetigo contagiosa [p=0.011]). Improvements in pain, quality of life, (Freiburg Life Quality Assessment), and Eczema Area and Severity Index scores were also seen. Treatment was well tolerated; most frequent adverse events were burning (14%) or itching (9%) sensations. Thus, liposomal PVP-iodine hydrogel has potential utility as an effective treatment for inflammatory skin conditions associated with bacterial colonization. PMID- 28989282 TI - Spotlight on eluxadoline for the treatment of patients with irritable bowel syndrome with diarrhea. AB - BACKGROUND: Irritable bowel syndrome with diarrhea (IBS-D) has limited options for treatment currently, including mainly anti-motility medications, antispasmodics, and antidepressants. This review discusses the properties of a new drug, eluxadoline, a gut-targeting mu- and kappa-opioid receptor agonist and a delta-opioid receptor antagonist, and its efficacy and safety in patients with IBS-D. MATERIALS AND METHODS: A systematic review of the literature was undertaken to identify studies that had investigated eluxadoline as a treatment in IBS-D. A narrative review of other information is provided with respect to pharmacological and chemical properties. Where suitable, meta-analysis was performed with a random-effects model to produce a pooled estimate. RESULTS: Eluxadoline showed efficacy improving stool consistency (standardized mean difference [SMD]: -0.29 at 12 weeks, p = 0.0004; -0.46 at 26 weeks, p = 0.0001), global symptoms (SMD: -0.15 at 12 weeks, p = 0.006; -0.14 at 26 weeks, p = 0.02), quality of life (SMD: 0.21 at 12 weeks, p < 0.0001; 0.16 at 26 weeks, p = 0.007), pain (SMD: -0.17 at 12 weeks, p = 0.001; -0.16 at 26 weeks, p = 0.01), and adequate relief (odds ratio [OR]: 1.99 at 12 weeks, p < 0.00001; 1.78 at 26 weeks, p < 0.0001). It also improved IBS severity and other abdominal symptoms such as bloating, discomfort, and risk of urgency and fecal incontinence. Its main side effects included constipation (OR: 3.49, p < 0.00001), vomiting (OR: 3.42, p = 0.0002), abdominal pain (OR: 1.78, p = 0.007), and nausea (OR: 1.42, p = 0.07). The overall quality of trials was satisfactory with the meta-analyses providing largely homogeneous outcomes. CONCLUSION: Eluxadoline's place in clinical practice might prove useful since the pharmacological options of IBS-D are limited and eluxadoline showed a positive effect in treating the symptoms of IBS-D. PMID- 28989283 TI - Abdominal pain and nausea in the diagnosis of streptococcal pharyngitis in boys. AB - OBJECTIVES: This study was designed to assess the accuracy of gastrointestinal symptoms, including abdominal pain, nausea, and vomiting, in the diagnosis of Group A streptococcal (GAS) pharyngitis in children and to determine differences in diagnostic accuracy in boys versus girls. METHODS: This retrospective cross sectional study included 5,755 consecutive patients aged <15 years with fever in the electronic database at a primary care practice. Gastrointestinal symptoms were recorded in the database according to the International Classification of Primary Care codes, and the data were extracted electronically. The reference standard was GAS pharyngitis diagnosed with a rapid test. Patients with a clinical diagnosis of probable GAS pharyngitis were excluded from the primary analysis. RESULTS: Among the 5,755 children with fever, 331 (5.8%) were coded as having GAS pharyngitis, including 218 (65.9%) diagnosed with rapid tests and 113 (34.1%) clinically diagnosed with probable GAS pharyngitis. Among patients with fever and abdominal pain, rapid-test-confirmed GAS pharyngitis was significantly more common in boys (11/120, 9.2%) than in girls (3/128, 2.3%; p=0.026). The positive likelihood ratio of abdominal pain was 1.49 (95% CI =0.88-2.51): 2.41 (95% CI =1.33-4.36) in boys and 0.63 (95% CI =0.20-1.94) in girls. The positive likelihood ratio of nausea was 2.05 (95% CI =1.06-4.00): 2.74 (95% CI =1.28-5.86) in boys and 1.09 (95% CI =0.27-4.42) in girls. The association between abdominal pain and GAS pharyngitis was stronger in boys aged <6 years than in boys aged 6 15 years. CONCLUSION: Abdominal pain and nausea were associated with GAS pharyngitis in boys, but not in girls. Abdominal pain and nausea may help determine the suitability of rapid tests in younger boys with fever and other clinical findings consistent with GAS pharyngitis, even in the absence of sore throat. PMID- 28989284 TI - An Exploration Into Short-Interval Maintenance of Adult Hemispheric Cortical Thickness at an Individual Brain Level. AB - Adult cerebral cortical structure is thought to be statically maintained over short intervals. This view is based on group average findings but has never been studied at the individual level. This issue was examined with an unconventional longitudinal magnetic resonance imaging design which measured hemispheric mean cortical thickness of an adult man repeatedly at week intervals over 6 months. These measures were compared with measurement error estimates to test the current prediction that thickness measures would be statically maintained within measurement error variation. The results did not support this prediction. Thickness underwent incremental and decremental fluctuations which ranged up to 0.12 mm and 5.83% over week and multiweek intervals and which differed from measurement error variation. These exploratory analyses suggest a working hypothesis that short-interval cortical structural maintenance in an individual can involve fluctuations in thickness. If confirmed, this hypothesis has potential implications for cortical maintenance mechanisms and precision medicine approaches. PMID- 28989285 TI - Unintended target effect of anti-BCL-2 DNAi. AB - INTRODUCTION: Previous research suggested that a novel compound PNT2258 inhibits B-cell lymphoma 2 (BCL-2) transcription by DNA interference (DNAi) and demonstrated its activity in preclinical xenograft models and in a pilot Phase II clinical trial in non-Hodgkin's lymphoma (NHL). While the drug downregulates BCL 2 at the promoter, mRNA, and protein levels, there is a significant homology (13 16 bases) between PNT100 and a number of promoters of genes involved in cell cycle regulation and survival. In this study, we identify cyclin-dependent kinase 4 (CDK4) as an unintended target gene of PNT2258 and examine its relevance to NHL. METHODS: We performed a Basic Local Alignment Search Tool (BLAST) homology search using PNT100 DNAi sequences. Also, we conducted CDK4 promoter assay in K562 cells and studied the protein expression of CDK4 in Wayne State University (WSU)-follicular small cleaved cell lymphoma (FSCCL), WSU-diffuse large cell lymphoma, and WSU-Waldenstrom's macroglobulinemia (WM) lymphoma cells. RESULTS: BLAST homology search showed that PNT100 completely binds to BCL-2 gene as expected. However, there was 100% homology in a stretch of 14 bases (8-21) between PNT100 and CDK4. PNT2258 strongly inhibited CDK4 promoter activity in K562 cells. Moreover, CDK4 protein expression was significantly downregulated by PNT2258 in WSU-FSCCL and WSU-WM cell lines. DISCUSSION: DNAi may work not only through knocking down the intended gene but also by knocking down other genes. PNT2258 affects CDK4 expression and promoter activity. Results of the present study suggest a broader mechanism of action for DNAi targeting both intended (BCL 2) and unintended (CDK4) genes. PMID- 28989286 TI - Effect of late HIV diagnosis on HIV-related mortality among adults in general hospitals of Central Zone Tigray, northern Ethiopia: a retrospective cohort study. AB - BACKGROUND: The global incidence of HIV infection is not significantly decreasing, especially in sub-Saharan African countries, including Ethiopia. Though there is availability and accessibility of free HIV services, people are not being diagnosed early for HIV, and hence patients are still dying of HIV related causes. This research is aimed at verifying the effect of late diagnosis of HIV on HIV-related mortality in Central Zone Tigray, Ethiopia. METHODS: A retrospective cohort study among adult (>=15 years old) HIV patients in three general hospitals of Tigray was conducted. Record reviews were carried out retrospectively from 2010 to 2015. Sample size was determined using stpower Cox in Stata software. Data were entered into EpiData version 3.1 software and transferred to Stata version 12 for analysis. Both bivariable and multivariable analyses were performed using Cox regression model to compare the HIV-related mortality of exposed (cluster of differentiation 4 cells count <350 cells/mm3) and nonexposed (>=350 cells/mm3) patients using adjusted hazard ratio (AHR) at 95% confidence interval (CI). RESULT: In all, 638 HIV patients were analyzed, contributing 2,105.6 person-years. Forty-eight (7.5%) patients died of HIV related causes with a mortality rate of 2.28 per 100 person-years. In the multivariable Cox regression model, patients with late diagnosis of HIV had a higher risk of mortality (AHR =3.22, 95% CI: 1.17-8.82) than patients with early diagnosis of HIV. Rural residence (AHR =1.96, 95% CI: 1.05-3.68), unemployment (AHR =2.70, 95% CI: 1.03-7.08), bedridden patients (AHR =2.98, 95% CI: 1.45 6.13), ambulatory patients (AHR =2.54, 95% CI: 1.05-6.15), and baseline hemoglobin level of <11 mg/dL (AHR =3.06, 95% CI: 1.51-6.23) were other independent predictors of mortality. CONCLUSION AND RECOMMENDATIONS: Late diagnosis of HIV increased HIV-related mortality. Rural residence, unemployment, bedridden and ambulatory patients, and baseline hemoglobin level <11 mg/dL were also independent predictors of HIV-related mortality. PMID- 28989287 TI - Congenitally corrected transposition of great vessels with infundibular pulmonary stenosis with ventricular septal defect, presenting with atypical atrioventricular nodal reentrant tachycardia: a rare association. AB - Congenitally corrected transposition of great vessels (CCTGV) is a rare congenital heart disease (CHD) accounting for <1% of CHDs. CCTGV with infundibular pulmonary stenosis (PS) with ventricular septal defect (VSD) is part of Fallot's physiology. It is known to be associated with bradyarrhythmias like atrioventricular (AV) blocks, and acquired complete AV block occurs at a rate of 2% per year. Patients can have left-sided accessory pathways, which may cause atrioventricular reentrant tachycardia (AVRT). Tachyarrhythmias like atrioventricular nodal reentrant tachycardia (AVNRT) are very rare in such patients. A 30-year-old woman, a known case of CCTGV with PS with VSD, not corrected surgically and not on any drugs, presented with the syndrome of paroxysmal supraventricular tachycardia without hemodynamic compromise. Electrocardiogram showed atypical AVNRT. She was pharmacologically cardioverted to normal sinus rhythm with adenosine. CTGV with PS with VSD known to be associated with AV blocks, and preexcitation can sometimes present with atypical AVNRT. PMID- 28989288 TI - A Family of Early English Oculists (1600-1751), With a Reappraisal of John Thomas Woolhouse (1664-1733/1734). AB - INTRODUCTION: John Thomas Woolhouse (1666-1733/1734), who practiced in Paris, was part of a family with 5 generations of English oculists. Some historians have derided him as a "charlatan" and have criticized him for adhering to the old notion that a cataract was a membrane anterior to the lens. METHODS: We reviewed treatises and digital records related to Woolhouse and his family and the handwritten notes of his 1721 lecture series at the Royal Society of Medicine. RESULTS: We have identified 5 generations of oculists in Woolhouse's family, by the names of Atwood, Stepkins, Ivy, and Beaumont. Woolhouse taught students from across Europe. He was one of the early proponents in Europe, inspired by Asian medical practices, to perform paracentesis to release aqueous for a new condition called hydrophthalmia. In Woolhouse's system, some of these cases probably described angle-closure glaucoma. He was the first to attach the name glaucoma to the palpably hard eye in 1707. He may also have been the first to teach that a soft eye was unlikely to recover vision. Credit for these teachings has traditionally gone to one of his students, Johannes Zacharias Platner, in 1745. Some historians have stated that he proposed iridectomy as a theoretical procedure, which was later performed by Cheselden. In fact, Woolhouse described techniques he had performed which today would be called pupilloplasty, synechiolysis, or pupillary membrane lysis. He was also a pioneer in dacryocystectomy for chronic dacryocystitis and in congenital cataract surgery. His writings from 1716 onward repeatedly (and correctly) stressed that most of the patients with visual disorders required depression of the crystalline lens (for what he called glaucoma), as opposed to removal of an anterior membrane (which he called cataract). CONCLUSIONS: Woolhouse was a bold ophthalmic innovator and teacher who made major contributions which have lasted to this day. Although he did not admit it, he ultimately adopted much of the evolving understanding of the nature of lens opacities. However, his stubborn refusal to adopt the newer semantics has detracted from a full appreciation of his contributions. PMID- 28989290 TI - Feasibility of the Atlas Unicompartmental Knee System Load Absorber in Improving Pain Relief and Function in Patients Needing Unloading of the Medial Compartment of the Knee: 1-Year Follow-Up of a Prospective, Multicenter, Single-Arm Pilot Study (PHANTOM High Flex Trial). AB - In young patients with medial knee osteoarthritis (OA), surgical intervention may not be desirable due to preferences to avoid bone cutting procedures, return to high activity levels, and prolong implant survival. The Atlas Knee System was designed to fill the gap between ineffective conservative treatments and invasive surgery. This single-arm study included 26 patients, aged 25 to 65 years, who completed 12 months of follow-up. All dimensions of the Knee injury and Osteoarthritis Outcome Score (KOOS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Knee Society Score significantly improved from baseline to 12 months. About 96.2% and 92.3% of patients experienced a ?20% improvement in their KOOS pain and WOMAC pain scores, respectively, at 12 months. This study highlights the potential benefit of a joint unloading device in the management of young patients with medial knee OA. The trial is still ongoing and another analysis is planned at 24 months. PMID- 28989292 TI - Diffusion in Tube Dialyzer. AB - Nowadays, kidney failure is a problem of many peoples in the world. We know that the main function of kidney is maintaining the chemical quality of blood particularly removing urea through urine. But when they malfunction, the pathologic state known as uremia results in a condition in which the urea is retained in the body. Failure of the kidney results in building up of harmful wastes and excess fluids in the body. Kidney diseases (failures) can be due to infections, high blood pressure (hypertension), diabetes, and/or extensive use of medication. The best form of treatment is the implantation of a healthy kidney from a donor. However, this is often not possible due to the limited availability of human organs. Chronic kidney failure requires the treatment using a tube dialyzer called dialysis. Blood is taken out of the body and passes through a special membrane that removes waste and extra fluids. The clean blood is then returned to the body. The process is controlled by a dialysis machine (tube dialyzer) which is equipped with a blood pump and monitoring systems to ensure safety. So this article investigates the real application of mathematics (diffusion) in medical science, and it also contains the mathematical formulation and interpretation of tube dialyzer in relation to diffusion. PMID- 28989289 TI - Epidemiology, diagnosis, and optimal management of glioma in adolescents and young adults. AB - Neoplasms of the central nervous system (CNS) are the most frequently encountered solid tumors of childhood, but are less common in adolescents and young adults (AYA), aged 15-39 years. Gliomas account for 29%-35% of the CNS tumors in AYA, with approximately two-thirds being low-grade glioma (LGG) and the remaining being high-grade glioma (HGG). We review the epidemiology, work-up, and management of LGG and HGG, focusing on the particular issues faced by the AYA population relative to pediatric and adult populations. Visual pathway glioma and brainstem glioma, which represent unique clinical entities, are only briefly discussed. As a general management approach for both LGG and HGG, maximal safe resection should be attempted. AYA with LGG who undergo gross total resection (GTR) may be safely observed. As age increases and the risk factors for recurrence accumulate, adjuvant therapy should be more strongly considered with a strong consideration of advanced radiation techniques such as proton beam therapy to reduce long-term radiation-related toxicity. Recent results also suggest survival advantage for adult patients with the use of adjuvant chemotherapy when radiation is indicated. Whenever possible, AYA patients with HGG should be enrolled in a clinical trial for the benefit of centralized genetic and molecular prognostic review and best clinical care. Chemoradiation should be offered to all World Health Organization grade IV patients with concurrent and adjuvant chemotherapy after maximal safe resection. Younger adolescents with GTR of grade III lesions may consider radiotherapy alone or sequential radiotherapy and chemotherapy if unable to tolerate concurrent treatment. A more comprehensive classification of gliomas integrating pathology and molecular data is emerging, and this integrative strategy offers the potential to be more accurate and reproducible in guiding diagnostic, prognostic, and management decisions. PMID- 28989291 TI - Frontline Therapy for Classical Hodgkin Lymphoma by Stage and Prognostic Factors. AB - Hodgkin lymphoma is a highly curable malignancy in early and advanced stages. Most patients are diagnosed in their teens or twenties and are expected to live decades beyond their treatment. Therefore, the toxicity of treatment must be balanced with the goal of cure. Thus, treatment has been refined through prognostic models and positron emission tomography-computed tomography (PET-CT) directed therapy. Stratification by prognostic models defines groups of patients with favorable characteristics who may be treated with less intensive therapy upfront, including fewer cycles of chemotherapy, lower doses of radiation, or omission of radiation altogether. Alternatively, high-risk patients may be assigned to a more aggressive initial approach. The modern use of interim PET-CT allows further tailoring of treatment by response. PMID- 28989293 TI - Internet use and its addiction level in medical students. AB - OBJECTIVE: To compare the Internet addiction levels between male and female medical students. METHODS: One hundred medical students (male: 50, female: 50) aged 17-30 years were included in a cross-sectional study. A standardized questionnaire was used to assess their Internet addiction level. Additionally, a self-designed questionnaire was used to identify the various purposes of Internet use among the students. The Internet addiction score (based on the Internet Addiction Test) was compared between male and female students by using the Mann Whitney U test (p<=0.05). After knowing their addiction level, we interviewed students to know if Internet use had any bad/good impact on their life. RESULTS: The Internet Addiction Test scores obtained by the students were in the range of 11-70. Out of 100 students, 21 (male: 13, female: 8) were found to be slightly addicted to the Internet. The remaining 79 students were average online users. There was no significant difference between male and female students in the addiction level (score). However, males were more addicted than females. The major use of Internet was to download and watch movies and songs and to communicate with friends and family (76/100). Some students (24/100) used the Internet to assess information that helped them in their educational and learning activities. Some students mentioned that overuse of the Internet lead to insufficient amounts of sleep and affected their concentration levels in the classroom during lectures. CONCLUSION: Medical students are experiencing problems due to Internet overuse. They experience poor academic progress and lack of concentration while studying. The main use of the Internet was for entertainment and to communicate with friends and family. PMID- 28989294 TI - What are the educational and curriculum needs for emergency medical technicians in Taiwan? A scoping review. AB - PURPOSE: The development of emergency medical services (EMS) training in Taiwan is in a transitional phase because of increasing demand for, and advancements in, clinical skill sets. The aim of this study is to review the current literature to compare the key factors of EMS training and education development in different countries in order to provide a new curricula blueprint for the Taiwanese EMS training system. METHOD: The method follows Arksey and O'Malley's six stages of scoping review. RESULTS: Five databases were searched for relevant articles: MEDLINE, EMBASE, Allied and Complementary Medicine Database; Education Resources Information Center, and Google Scholar. The initial search of five databases produced 1,230 articles, of which title and abstract screening excluded 1,156 articles. The 74 remaining articles underwent a full-text screening process, which further reduced the number of articles to 22. Researching references and citations produced an additional 23 articles, national curriculum standards produced a further six documents, and one article derived from emergency medical technician (EMT) regulation in Taiwan. In total, 52 articles were included in the study, categorized by competency and standards, EMT education and learning environment, curriculum design, and teaching and learning method. CONCLUSION: This study reviewed international EMS training and education literature and documents to summarize the essential elements for developing an EMS education system: for example, core competencies and standards, education environment, curriculum design, and teaching and learning method. By connecting the essential elements for developing an EMS education system, a blueprint for the Taiwanese EMS education system can be identified. Analysis and study of the essential elements will provide educators with clear direction in developing the EMS education system in Taiwan. PMID- 28989295 TI - Involving junior doctors in medical article publishing: is it an effective method of teaching? AB - BACKGROUND: Having peer-reviewed articles published in medical journals is important for career progression in many medical specialties. Despite this, only a minority of junior doctors have the skills in the area of medical article publishing. The aim of this study was to assess junior doctors' views concerning being involved in medical article publishing and whether they perceive involvement as an effective method of teaching. METHODS: A cross-sectional survey was administered to a convenience sample of doctors who had been involved in medical article publishing. Questions concerned training and involvement in publishing as junior doctors, effects on education and training, is it an effective method of teaching and should publishing be part of their education and training program. Questions used the 5-point Likert scale. Of the 39 doctors, 37 (94.9%) doctors responded. RESULTS: Only one-third of respondents agreed that they had adequate training or involvement in medical article publishing during their undergraduate medical training. Many (78.4%) agreed that it was difficult to get published as a junior doctor. Publishing as a junior doctor improved knowledge about publishing, understanding of the topic and interest in the field of study for 92, 92 and 73% of respondents, respectively. Many (89%) agreed that publishing made them eager to publish more. Most (76%) agreed that it was likely to encourage interest in a postgraduate career in that field of study. A majority (92%) felt that involvement in medical article publishing is an effective method of teaching and it should be a part of the junior doctors' education and training program. CONCLUSION: Junior doctors feel that involvement in medical article publishing contributes to learning and education and is an effective method of teaching. This supports the need to incorporate such training into the junior doctors' education and training program. PMID- 28989297 TI - New records for millipedes from southern Chile (Polydesmida: Dalodesmidae; Polyzoniida: Siphonotidae). AB - BACKGROUND: Millipedes from 1983 collections by the author in southern Chile have been identified and registered as specimen lots at the Queen Victoria Museum and Art Gallery (QVMAG) in Launceston, Tasmania. NEW INFORMATION: Collection and specimen data from the new QVMAG specimen lots have been archived in Darwin Core format together with a KML file of occurrences. The 31 occurrence records in the Darwin Core Archive list 13 millipede taxa from 16 sites in Llanquihue and Osorno provinces, Chile. PMID- 28989296 TI - Mystery mushroom malingerers: Megaselia marquezi Hartop et al. 2015 (Diptera: Phoridae). AB - A mysterious female phorid fly, known for many years to be associated with fungal sporophores ("mushrooms") is identified as Megaselia marquezi Hartop et al. 2015. Male and female flies were collected emerging from the fungus Psathyrella candolleana (Fr.) Maire, and females were observed swarming over the sporophores. PMID- 28989298 TI - Who will attack the competitors? How political parties resolve strategic and collective action dilemmas in negative campaigning. AB - Negative campaigning presents parties with a collective action problem. While parties would prefer to have their competitors attacked, potential backlash effects from negative messages mean that individual politicians typically lack the incentives to carry out such attacks. We theorize that parties solve this problem by implementing a division of labour that takes into account the incentives of individual office holders, their availability for campaign activity, and media relevance. Drawing on these arguments we expect that holders of high public office and party leaders are less likely to issue attacks, leaving the bulk of the 'dirty work' to be carried out by party floor leaders and general secretaries. Examining almost 8000 press releases issued by over 600 individual politicians during four election campaigns in Austria, we find strong support for our theoretical expectations. PMID- 28989299 TI - Transfection in perfused microfluidic cell culture devices: A case study. AB - Automated microfluidic devices are a promising route towards a point-of-care autologous cell therapy. The initial steps of induced pluripotent stem cell (iPSC) derivation involve transfection and long term cell culture. Integration of these steps would help reduce the cost and footprint of micro-scale devices with applications in cell reprogramming or gene correction. Current examples of transfection integration focus on maximising efficiency rather than viable long term culture. Here we look for whole process compatibility by integrating automated transfection with a perfused microfluidic device designed for homogeneous culture conditions. The injection process was characterised using fluorescein to establish a LabVIEW-based routine for user-defined automation. Proof-of-concept is demonstrated by chemically transfecting a GFP plasmid into mouse embryonic stem cells (mESCs). Cells transfected in the device showed an improvement in efficiency (34%, n = 3) compared with standard protocols (17.2%, n = 3). This represents a first step towards microfluidic processing systems for cell reprogramming or gene therapy. PMID- 28989301 TI - Density of convex intersections and applications. AB - In this paper, we address density properties of intersections of convex sets in several function spaces. Using the concept of Gamma-convergence, it is shown in a general framework, how these density issues naturally arise from the regularization, discretization or dualization of constrained optimization problems and from perturbed variational inequalities. A variety of density results (and counterexamples) for pointwise constraints in Sobolev spaces are presented and the corresponding regularity requirements on the upper bound are identified. The results are further discussed in the context of finite-element discretizations of sets associated with convex constraints. Finally, two applications are provided, which include elasto-plasticity and image restoration problems. PMID- 28989300 TI - Study of Crystal Formation and Nitric Oxide (NO) Release Mechanism from S-Nitroso N-acetylpenicillamine (SNAP)-Doped CarboSil Polymer Composites for Potential Antimicrobial Applications. AB - Stable and long-term nitric oxide (NO) releasing polymeric materials have many potential biomedical applications. Herein, we report the real-time observation of the crystallization process of the NO donor, S-nitroso-N-acetylpenicillamine (SNAP), within a thermoplastic silicone-polycarbonate-urethane biomedical polymer, CarboSil 20 80A. It is demonstrated that the NO release rate from this composite material is directly correlated with the surface area that the CarboSil polymer film is exposed to when in contact with aqueous solution. The decomposition of SNAP in solution (e.g. PBS, ethanol, THF, etc.) is a pseudo first-order reaction proportional to the SNAP concentration. Further, catheters fabricated with this novel NO releasing composite material are shown to exhibit significant effects on preventing biofilm formation on catheter surface by Pseudomonas aeruginosa and Proteus mirabilis grown in CDC bioreactor over 14 days, with a 2 and 3 log-unit reduction in number of live bacteria on their surfaces, respectively. Therefore, the SNAP-CarboSil composite is a promising new material to develop antimicrobial catheters, as well as other biomedical devices. PMID- 28989302 TI - On the Keller-Rubinow model for Liesegang ring formation. AB - We study the model of Keller & Rubinow (Keller & Rubinow 1981 J. Chem. Phys74, 5000-5007. (doi:10.1063/1.441752)) describing the formation of Liesegang rings due to Ostwald's supersaturation mechanism. Keller and Rubinow provided an approximate solution both for the growth and equilibration of the first band, and also for the formation of secondary bands, based on a presumed asymptotic limit. However, they did not provide a parametric basis for the assumptions in their solution, nor did they provide any numerical corroboration, particularly of the secondary band formation. Here, we provide a different asymptotic solution, based on a specific parametric limit, and we show that the growth and subsequent cessation of the first band can be explained. We also show that the model is unable to explain the formation of finite width secondary bands, and we confirm this result by numerical computation. We conclude that the model is not fully posed, lacking a transition variable which can describe the hysteretic switch across the nucleation threshold. PMID- 28989303 TI - Bitwise efficiency in chaotic models. AB - Motivated by the increasing energy consumption of supercomputing for weather and climate simulations, we introduce a framework for investigating the bit-level information efficiency of chaotic models. In comparison with previous explorations of inexactness in climate modelling, the proposed and tested information metric has three specific advantages: (i) it requires only a single high-precision time series; (ii) information does not grow indefinitely for decreasing time step; and (iii) information is more sensitive to the dynamics and uncertainties of the model rather than to the implementation details. We demonstrate the notion of bit-level information efficiency in two of Edward Lorenz's prototypical chaotic models: Lorenz 1963 (L63) and Lorenz 1996 (L96). Although L63 is typically integrated in 64-bit 'double' floating point precision, we show that only 16 bits have significant information content, given an initial condition uncertainty of approximately 1% of the size of the attractor. This result is sensitive to the size of the uncertainty but not to the time step of the model. We then apply the metric to the L96 model and find that a 16-bit scaled integer model would suffice given the uncertainty of the unresolved sub grid-scale dynamics. We then show that, by dedicating computational resources to spatial resolution rather than numeric precision in a field programmable gate array (FPGA), we see up to 28.6% improvement in forecast accuracy, an approximately fivefold reduction in the number of logical computing elements required and an approximately 10-fold reduction in energy consumed by the FPGA, for the L96 model. PMID- 28989304 TI - The problem of camouflaging via mirror reflections. AB - This work is related to billiards and their applications in geometric optics. It is known that perfectly invisible bodies with mirror surface do not exist. It is, therefore, natural to search for bodies that are, in a sense, close to invisible. We introduce a visibility index of a body measuring the mean angle of deviation of incident light rays, and derive a lower estimate for this index. This estimate is a function of the body's volume and of the minimal radius of a ball containing the body. This result is far from being final and opens a possibility for further research. PMID- 28989305 TI - Fully localized post-buckling states of cylindrical shells under axial compression. AB - We compute nonlinear force equilibrium solutions for a clamped thin cylindrical shell under axial compression. The equilibrium solutions are dynamically unstable and located on the stability boundary of the unbuckled state. A fully localized single dimple deformation is identified as the edge state-the attractor for the dynamics restricted to the stability boundary. Under variation of the axial load, the single dimple undergoes homoclinic snaking in the azimuthal direction, creating states with multiple dimples arranged around the central circumference. Once the circumference is completely filled with a ring of dimples, snaking in the axial direction leads to further growth of the dimple pattern. These fully nonlinear solutions embedded in the stability boundary of the unbuckled state constitute critical shape deformations. The solutions may thus be a step towards explaining when the buckling and subsequent collapse of an axially loaded cylinder shell is triggered. PMID- 28989306 TI - Meso-scale defect evaluation of selective laser melting using spatially resolved acoustic spectroscopy. AB - Developments in additive manufacturing technology are serving to expand the potential applications. Critical developments are required in the supporting areas of measurement and in process inspection to achieve this. CM247LC is a nickel superalloy that is of interest for use in aerospace and civil power plants. However, it is difficult to process via selective laser melting (SLM) as it suffers from cracking during rapid cooling and solidification. This limits the viability of CM247LC parts created using SLM. To quantify part integrity, spatially resolved acoustic spectroscopy (SRAS) has been identified as a viable non-destructive evaluation technique. In this study, a combination of optical microscopy and SRAS was used to identify and classify the surface defects present in SLM-produced parts. By analysing the datasets and scan trajectories, it is possible to correlate morphological information with process parameters. Image processing was used to quantify porosity and cracking for bulk density measurement. Analysis of surface acoustic wave data showed that an error in manufacture in the form of an overscan occurred. Comparing areas affected by overscan with a bulk material, a change in defect density from 1.17% in the bulk material to 5.32% in the overscan regions was observed, highlighting the need to reduce overscan areas in manufacture. PMID- 28989307 TI - The steady aerodynamics of aerofoils with porosity gradients. AB - This theoretical study determines the aerodynamic loads on an aerofoil with a prescribed porosity distribution in a steady incompressible flow. A Darcy porosity condition on the aerofoil surface furnishes a Fredholm integral equation for the pressure distribution, which is solved exactly and generally as a Riemann Hilbert problem provided that the porosity distribution is Holder-continuous. The Holder condition includes as a subset any continuously differentiable porosity distributions that may be of practical interest. This formal restriction on the analysis is examined by a class of differentiable porosity distributions that approach a piecewise, discontinuous function in a certain parametric limit. The Holder-continuous solution is verified in this limit against analytical results for partially porous aerofoils in the literature. Finally, a comparison made between the new theoretical predictions and experimental measurements of SD7003 aerofoils presented in the literature. Results from this analysis may be integrated into a theoretical framework to optimize turbulence noise suppression with minimal impact to aerodynamic performance. PMID- 28989308 TI - Rate-based structural health monitoring using permanently installed sensors. AB - Permanently installed sensors are becoming increasingly ubiquitous, facilitating very frequent in situ measurements and consequently improved monitoring of 'trends' in the observed system behaviour. It is proposed that this newly available data may be used to provide prior warning and forecasting of critical events, particularly system failure. Numerous damage mechanisms are examples of positive feedback; they are 'self-accelerating' with an increasing rate of damage towards failure. The positive feedback leads to a common time-response behaviour which may be described by an empirical relation allowing prediction of the time to criticality. This study focuses on Structural Health Monitoring of engineering components; failure times are projected well in advance of failure for fatigue, creep crack growth and volumetric creep damage experiments. The proposed methodology provides a widely applicable framework for using newly available near continuous data from permanently installed sensors to predict time until failure in a range of application areas including engineering, geophysics and medicine. PMID- 28989309 TI - Singular diffusionless limits of double-diffusive instabilities in magnetohydrodynamics. AB - We study local instabilities of a differentially rotating viscous flow of electrically conducting incompressible fluid subject to an external azimuthal magnetic field. In the presence of the magnetic field, the hydrodynamically stable flow can demonstrate non-axisymmetric azimuthal magnetorotational instability (AMRI) both in the diffusionless case and in the double-diffusive case with viscous and ohmic dissipation. Performing stability analysis of amplitude transport equations of short-wavelength approximation, we find that the threshold of the diffusionless AMRI via the Hamilton-Hopf bifurcation is a singular limit of the thresholds of the viscous and resistive AMRI corresponding to the dissipative Hopf bifurcation and manifests itself as the Whitney umbrella singular point. A smooth transition between the two types of instabilities is possible only if the magnetic Prandtl number is equal to unity, Pm=1. At a fixed Pm?1, the threshold of the double-diffusive AMRI is displaced by finite distance in the parameter space with respect to the diffusionless case even in the zero dissipation limit. The complete neutral stability surface contains three Whitney umbrella singular points and two mutually orthogonal intervals of self intersection. At these singularities, the double-diffusive system reduces to a marginally stable system which is either Hamiltonian or parity-time-symmetric. PMID- 28989310 TI - Irreversible particle motion in surfactant-laden interfaces due to pressure dependent surface viscosity. AB - The surface shear viscosity of an insoluble surfactant monolayer often depends strongly on its surface pressure. Here, we show that a particle moving within a bounded monolayer breaks the kinematic reversibility of low-Reynolds-number flows. The Lorentz reciprocal theorem allows such irreversibilities to be computed without solving the full nonlinear equations, giving the leading-order contribution of surface pressure-dependent surface viscosity. In particular, we show that a disc translating or rotating near an interfacial boundary experiences a force in the direction perpendicular to that boundary. In unbounded monolayers, coupled modes of motion can also lead to non-intuitive trajectories, which we illustrate using an interfacial analogue of the Magnus effect. This perturbative approach can be extended to more complex geometries, and to two-dimensional suspensions more generally. PMID- 28989311 TI - Uncertainties in the 2004 Sumatra-Andaman source through nonlinear stochastic inversion of tsunami waves. AB - Numerical inversions for earthquake source parameters from tsunami wave data usually incorporate subjective elements to stabilize the search. In addition, noisy and possibly insufficient data result in instability and non-uniqueness in most deterministic inversions, which are barely acknowledged. Here, we employ the satellite altimetry data for the 2004 Sumatra-Andaman tsunami event to invert the source parameters. We also include kinematic parameters that improve the description of tsunami generation and propagation, especially near the source. Using a finite fault model that represents the extent of rupture and the geometry of the trench, we perform a new type of nonlinear joint inversion of the slips, rupture velocities and rise times with minimal a priori constraints. Despite persistently good waveform fits, large uncertainties in the joint parameter distribution constitute a remarkable feature of the inversion. These uncertainties suggest that objective inversion strategies should incorporate more sophisticated physical models of seabed deformation in order to significantly improve the performance of early warning systems. PMID- 28989313 TI - On the topology of the Lorenz system. AB - We present a new paradigm for three-dimensional chaos, and specifically for the Lorenz equations. The main difficulty in these equations and for a generic flow in dimension 3 is the existence of singularities. We show how to use knot theory as a way to remove the singularities. Specifically, we claim: (i) for certain parameters, the Lorenz system has an invariant one-dimensional curve, which is a trefoil knot. The knot is a union of invariant manifolds of the singular points. (ii) The flow is topologically equivalent to an Anosov flow on the complement of this curve, and moreover to a geodesic flow. (iii) When varying the parameters, the system exhibits topological phase transitions, i.e. for special parameter values, it will be topologically equivalent to an Anosov flow on a knot complement. Different knots appear for different parameter values and each knot controls the dynamics at nearby parameters. PMID- 28989312 TI - Accuracy of the hypothetical sky-polarimetric Viking navigation versus sky conditions: revealing solar elevations and cloudinesses favourable for this navigation method. AB - According to Thorkild Ramskou's theory proposed in 1967, under overcast and foggy skies, Viking seafarers might have used skylight polarization analysed with special crystals called sunstones to determine the position of the invisible Sun. After finding the occluded Sun with sunstones, its elevation angle had to be measured and its shadow had to be projected onto the horizontal surface of a sun compass. According to Ramskou's theory, these sunstones might have been birefringent calcite or dichroic cordierite or tourmaline crystals working as polarizers. It has frequently been claimed that this method might have been suitable for navigation even in cloudy weather. This hypothesis has been accepted and frequently cited for decades without any experimental support. In this work, we determined the accuracy of this hypothetical sky-polarimetric Viking navigation for 1080 different sky situations characterized by solar elevation theta and cloudiness rho, the sky polarization patterns of which were measured by full-sky imaging polarimetry. We used the earlier measured uncertainty functions of the navigation steps 1, 2 and 3 for calcite, cordierite and tourmaline sunstone crystals, respectively, and the newly measured uncertainty function of step 4 presented here. As a result, we revealed the meteorological conditions under which Vikings could have used this hypothetical navigation method. We determined the solar elevations at which the navigation uncertainties are minimal at summer solstice and spring equinox for all three sunstone types. On average, calcite sunstone ensures a more accurate sky-polarimetric navigation than tourmaline and cordierite. However, in some special cases (generally at 35 degrees <= theta <= 40 degrees , 1 okta <= rho <= 6 oktas for summer solstice, and at 20 degrees <= theta <= 25 degrees , 0 okta <= rho <= 4 oktas for spring equinox), the use of tourmaline and cordierite results in smaller navigation uncertainties than that of calcite. Generally, under clear or less cloudy skies, the sky-polarimetric navigation is more accurate, but at low solar elevations its accuracy remains relatively large even at high cloudiness. For a given rho, the absolute value of averaged peak North uncertainties dramatically decreases with increasing theta until the sign (+/-) change of these uncertainties. For a given theta, this absolute value can either decrease or increase with increasing rho. The most advantageous sky situations for this navigation method are at summer solstice when the solar elevation and cloudiness are 35 degrees <= theta <= 40 degrees and 2 oktas <= rho <= 3 oktas. PMID- 28989314 TI - A priori estimation of memory effects in reduced-order models of nonlinear systems using the Mori-Zwanzig formalism. AB - Reduced models of nonlinear dynamical systems require closure, or the modelling of the unresolved modes. The Mori-Zwanzig procedure can be used to derive formally closed evolution equations for the resolved physics. In these equations, the unclosed terms are recast as a memory integral involving the time history of the resolved variables. While this procedure does not reduce the complexity of the original system, these equations can serve as a mathematically consistent basis to develop closures based on memory approximations. In this scenario, knowledge of the memory kernel is paramount in assessing the validity of a memory approximation. Unravelling the memory kernel requires solving the orthogonal dynamics, which is a high-dimensional partial differential equation that is intractable, in general. A method to estimate the memory kernel a priori, using full-order solution snapshots, is proposed. The key idea is to solve a pseudo orthogonal dynamics equation, which has a convenient Liouville form, instead. This ersatz arises from the assumption that the semi-group of the orthogonal dynamics is a composition operator for one observable. The method is exact for linear systems. Numerical results on the Burgers and Kuramoto-Sivashinsky equations demonstrate that the proposed technique can provide valuable information about the memory kernel. PMID- 28989316 TI - Stochastic partial differential fluid equations as a diffusive limit of deterministic Lagrangian multi-time dynamics. AB - In Holm (Holm 2015 Proc. R. Soc. A471, 20140963. (doi:10.1098/rspa.2014.0963)), stochastic fluid equations were derived by employing a variational principle with an assumed stochastic Lagrangian particle dynamics. Here we show that the same stochastic Lagrangian dynamics naturally arises in a multi-scale decomposition of the deterministic Lagrangian flow map into a slow large-scale mean and a rapidly fluctuating small-scale map. We employ homogenization theory to derive effective slow stochastic particle dynamics for the resolved mean part, thereby obtaining stochastic fluid partial equations in the Eulerian formulation. To justify the application of rigorous homogenization theory, we assume mildly chaotic fast small-scale dynamics, as well as a centring condition. The latter requires that the mean of the fluctuating deviations is small, when pulled back to the mean flow. PMID- 28989315 TI - On the differing growth mechanisms of black-smoker and Lost City-type hydrothermal vents. AB - Black smokers and Lost City-type springs are varieties of hydrothermal vents on the ocean floors that emit hot, acidic water and cool, alkaline water, respectively. While both produce precipitation structures as the issuing fluid encounters oceanic water, Lost City-type hydrothermal vents in particular have been implicated in the origin of life on the Earth. We present a parallel velocity flow model for the radius and flow rate of a cylindrical jet of fluid that forms the template for the growth of a tube precipitated about itself and we compare the solution with previous laboratory experimental results from growth of silicate chemical gardens. We show that when the growth of the solid structure is determined by thermal diffusion, fluid flow is slow at the solid-liquid contact. However, in the case of chemical diffusive transport, the fluid jet effectively drags the liquid in the pores of the solid precipitate. These findings suggest a continuum in the diffusive growth rate of hydrothermal vent structures, where Lost City-type hydrothermal vents favour contact between the vent fluid and the external seawater. We explore the implications for the road to life. PMID- 28989317 TI - Can a quantum state over time resemble a quantum state at a single time? AB - The standard formalism of quantum theory treats space and time in fundamentally different ways. In particular, a composite system at a given time is represented by a joint state, but the formalism does not prescribe a joint state for a composite of systems at different times. If there were a way of defining such a joint state, this would potentially permit a more even-handed treatment of space and time, and would strengthen the existing analogy between quantum states and classical probability distributions. Under the assumption that the joint state over time is an operator on the tensor product of single-time Hilbert spaces, we analyse various proposals for such a joint state, including one due to Leifer and Spekkens, one due to Fitzsimons, Jones and Vedral, and another based on discrete Wigner functions. Finding various problems with each, we identify five criteria for a quantum joint state over time to satisfy if it is to play a role similar to the standard joint state for a composite system: that it is a Hermitian operator on the tensor product of the single-time Hilbert spaces; that it represents probabilistic mixing appropriately; that it has the appropriate classical limit; that it has the appropriate single-time marginals; that composing over multiple time steps is associative. We show that no construction satisfies all these requirements. If Hermiticity is dropped, then there is an essentially unique construction that satisfies the remaining four criteria. PMID- 28989318 TI - Cautionary tales on air-quality improvement in Beijing. AB - The official air-quality statistic reported that Beijing had a 9.9% decline in the annual concentration of PM2.5 in 2016. While this statistic offered some relief for the inhabitants of the capital, we present several analyses based on Beijing's PM2.5 data of the past 4 years at 36 monitoring sites along with meteorological data of the past 7 years. The analyses reveal the air pollution situation in 2016 was not as rosy as the 9.9% decline would convey, and improvement if any was rather uncertain. The paper also provides an assessment on the city's PM2.5 situation in the past 4 years. PMID- 28989319 TI - Elastodynamic image forces on screw dislocations in the presence of phase boundaries. AB - The elastodynamic image forces acting on straight screw dislocations in the presence of planar phase boundaries are derived. Two separate dislocations are studied: (i) the injected, non-moving screw dislocation and (ii) the injected (or pre-existing), generally non-uniformly moving screw dislocation. The image forces are derived for both the case of a rigid surface and of a planar interface between two homogeneous, isotropic phases. The case of a rigid interface is shown to be solvable employing Head's image dislocation construction. The case of the elastodynamic image force due to an interface is solved by deriving the reflected wave's contribution to the global solution across the interface. This entails obtaining the fundamental solution (Green's function) for a point unit force via Cagniard's method, and then applying the convolution theorem for a screw dislocation modelled as a force distribution. Complete, explicit formulae are provided when available. It is shown that the elastodynamic image forces are generally affected by retardation effects, and that those acting on the moving dislocations display a dynamic magnification that exceed the attraction (or repulsion) predicted in classical elastostatic calculations. PMID- 28989320 TI - Nonparametric methods for doubly robust estimation of continuous treatment effects. AB - Continuous treatments (e.g., doses) arise often in practice, but many available causal effect estimators are limited by either requiring parametric models for the effect curve, or by not allowing doubly robust covariate adjustment. We develop a novel kernel smoothing approach that requires only mild smoothness assumptions on the effect curve, and still allows for misspecification of either the treatment density or outcome regression. We derive asymptotic properties and give a procedure for data-driven bandwidth selection. The methods are illustrated via simulation and in a study of the effect of nurse staffing on hospital readmissions penalties. PMID- 28989321 TI - 'Because I've been extremely careful': HIV seroconversion, responsibility, citizenship and the neo-liberal drug-using subject. AB - In this article we examine how injection drug users who do not attribute their HIV infection to engaging in HIV risk behaviours take up and critique discourses of individual responsibility and citizenship relating to HIV risk and HIV prevention. We draw on data from a study in Vancouver, Canada (2006 - 2009) in which we interviewed individuals living with HIV who had a history of injection drug use. In this paper we focus on 6 cases studies of participants who did not attribute their HIV infection to engaging in HIV risk behaviours. We found that in striving to present themselves as responsible HIV citizens who did not engage in HIV risk behaviours, these participants drew on individually-focused HIV prevention discourses. By identifying themselves in these ways, they were able to present themselves as 'deserving' HIV citizens and avoid the blame associated with being HIV positive. However, in rejecting the view that they and their risk behaviours were to blame for their HIV infection and by developing an explanation that drew on broader social, structural and historical factors, these individuals were developing a tentative critique of the importance of individual responsibility in HIV transmission as opposed to dangers of infection from the socio-economic environment. By framing the risk of infection in environmental rather than individual risk-behaviour terms these individuals redistributed responsibility to reflect the social-structural realities of their lives. In this article we reflect on the implications of these findings for public health measures such as risk prevention messages. We note that it is important that such messages are not restricted to individual risk prevention but also include a focus of broader shared responsibilities of HIV. PMID- 28989322 TI - Nonlocal teleparallel cosmology. AB - Even though it is not possible to differentiate general relativity from teleparallel gravity using classical experiments, it could be possible to discriminate between them by quantum gravitational effects. These effects have motivated the introduction of nonlocal deformations of general relativity, and similar effects are also expected to occur in teleparallel gravity. Here, we study nonlocal deformations of teleparallel gravity along with its cosmological solutions. We observe that nonlocal teleparallel gravity (like nonlocal general relativity) is consistent with the present cosmological data obtained by SNe Ia + BAO + CC + [Formula: see text] observations. Along this track, future experiments probing nonlocal effects could be used to test whether general relativity or teleparallel gravity gives the most consistent picture of gravitational interaction. PMID- 28989324 TI - Positive and Negative Aspects of Relationship Quality and Unprotected Sex among Young Women. AB - The aim of this study was to examine both positive and negative aspects of relationship quality in relation to condom use. Sexually active young women aged 14-18 years (n=111; 34% non-white) were recruited from community clinics and schools in the Midwest USA and provided data via an online survey. The number of unprotected sex acts in the past month with the most recent male partner was regressed on relationship quality with that partner, adjusting for demographics and other characteristics. Negative relationship quality was associated with a greater number of unprotected sex acts among women reporting a low level of positive relationship quality and among women taking hormonal/IUD contraception. Positive relationship quality was associated with unprotected sex among women who reported multiple partners in the past month. Both positive and negative aspects of relationship quality may confer risk for unprotected sex. This risk appears modified by patterns of contraceptive use and other sexual behaviours. Health professionals may be more effective in promoting condom use if they ask questions about both positive and negative aspects of young people's relationship quality and tailor their conversations based on the responses received. PMID- 28989325 TI - Contrast between Spain and the Netherlands in the hidden obstacles to re-entry into the labour market due to a criminal record. AB - This article aims at analysing the differences between European countries in the obstacles ex-offenders face due to having a criminal record. First, a comparative analytical framework is introduced that takes into account all the different elements that can lead to exclusion from the labour market by the dissemination of criminal record information. This model brings together social norms (macro level), social actors (meso level) and individual choices (micro level) in the same framework. Secondly, this model is used to compare the different impact of having a criminal record in Spain and the Netherlands. This comparison highlights three important findings: (1) the difference between norms of transparency/privacy and inclusive/exclusive ideals, (2) the significant role of social control agents, such as probation agencies and the ex-offenders' social network, in shaping the opportunities that they have, and (3) self-exclusion seems to be a key mechanism for understanding unsuccessful re-entry into the labour market. PMID- 28989323 TI - The relationship of sleep complaints risk factors with sleep phase, quality, and quantity in Japanese workers. AB - Numerous studies have determined that lifestyle factors (smoking, drinking, snacking, etc.) and the bedroom environment can influence sleep. We developed a new sleep scale-the 3-Dimensional Sleep Scale (3DSS)-which measures three elements of sleep: phase, quality, and quantity. The purpose of this study is to determine which risk factors of sleep complaints are associated with these sleep elements. Data were obtained from 366 Japanese day workers (302 men and 64 women). Sleep condition was assessed with the 3DSS, and we also assessed various habits within 2 h of going to bed, including smoking, drinking, snacking, caffeine intake, mobile phone use, and working. We also asked about bedroom environmental conditions (noise, lighting, and temperature and humidity). Multivariate logistic regression analysis using the backward selection method (likelihood ratio) was used, with 3DSS scores as the outcome (i.e., over or under the cutoff). The results showed that smoking was associated with significantly greater odds ratio [2.71 (1.65-4.44)] of disordered sleep phase, while lighting as well as temperature and humidity led to greater odds [3.67 (1.55-8.68), 1.93 (1.20-3.11)] of poor sleep quality. Finally, only noise was significantly related to greater odds [1.98 (1.13-3.46)] of low sleep quantity. These findings indicated the various risk factors of sleep complaints could be associated with different sleep elements. This might help in the effective treatment of sleep complaints. PMID- 28989326 TI - Developmental trajectories of offenders convicted of fraud: A follow-up to age 50 in a Dutch conviction cohort. AB - This study describes the criminal careers of offenders convicted of fraud, distinguishing different career dimensions such as intermittency, versatility and specialization. Results indicate that most fraud offenders are versatile in the sense that they also have significant criminal records for other serious offending (that is, not fraud). At the same time they are also specialized in fraud. When we examine developmental trajectories of serious offending and next explore patterns of fraud for the groups identified, we find that offenders in our sample represent a heterogeneous group and that the classic divide between typical financial (for example, white-collar) offenders and common criminals does not apply to the majority of our sample. PMID- 28989327 TI - Beyond individualism: Is there a place for relational autonomy in clinical practice and research? AB - The dominant, individualistic understanding of autonomy that features in clinical practice and research is underpinned by the idea that people are, in their ideal form, independent, self-interested and rational gain-maximising decision-makers. In recent decades, this paradigm has been challenged from various disciplinary and intellectual directions. Proponents of 'relational autonomy' in particular have argued that people's identities, needs, interests - and indeed autonomy - are always also shaped by their relations to others. Yet, despite the pronounced and nuanced critique directed at an individualistic understanding of autonomy, this critique has had very little effect on ethical and legal instruments in clinical practice and research so far. In this article, we use four case studies to explore to what extent, if at all, relational autonomy can provide solutions to ethical and practical problems in clinical practice and research. We conclude that certain forms of relational autonomy can have a tangible and positive impact on clinical practice and research. These solutions leave the ultimate decision to the person most affected, but encourage and facilitate the consideration of this person's care and responsibility for connected others. PMID- 28989328 TI - NETWORK-BASED GENOME WIDE STUDY OF HIPPOCAMPAL IMAGING PHENOTYPE IN ALZHEIMER'S DISEASE TO IDENTIFY FUNCTIONAL INTERACTION MODULES. AB - Identification of functional modules from biological network is a promising approach to enhance the statistical power of genome-wide association study (GWAS) and improve biological interpretation for complex diseases. The precise functions of genes are highly relevant to tissue context, while a majority of module identification studies are based on tissue-free biological networks that lacks phenotypic specificity. In this study, we propose a module identification method that maps the GWAS results of an imaging phenotype onto the corresponding tissue specific functional interaction network by applying a machine learning framework. Ridge regression and support vector machine (SVM) models are constructed to re prioritize GWAS results, followed by exploring hippocampus-relevant modules based on top predictions using GWAS top findings. We also propose a GWAS top-neighbor based module identification approach and compare it with Ridge and SVM based approaches. Modules conserving both tissue specificity and GWAS discoveries are identified, showing the promise of the proposal method for providing insight into the mechanism of complex diseases. PMID- 28989329 TI - Probability of an Autism Diagnosis by Gestational Age. AB - Early preterm infants (EPT) (<33 6/7 weeks) are at increased risk for autism spectrum disorders (ASDs) but prevalence estimates vary widely across studies. Furthermore, there are very few studies addressing the association between late preterm (LPT) births (34-36 6/7 weeks) and ASDs. To address the question of whether LPT infants carry the same risk for ASDs as full-term infants, this study aimed to estimate the relative probability of an ASD diagnosis using Bayes rule. A retrospective cohort analysis of 406 children was undertaken to look at gestational age, ASDs, and birth history. The application of Bayes rule was used, given that there is not sufficient information about the joint probabilities related to prematurity and autism. Using the estimated gestational age proportions within ASD diagnosis, plus national estimates of ASDs, probabilities for ASDs within a given gestational age were calculated. Among these 406 children with ASDs, 6.7% were EPT and 10.6% were LPT. In comparison to full term, EPT children are at 1.9 multiplicative increase in risk (95% CI [1.3, 2.5]). While the probability of ASDs for LPT children was higher than that for term, the estimated relative risk of the LPT infants was not statistically significant (95% CI [0.9, 1.5]). EPT infants were significantly more likely to be diagnosed with ASDs compared to their term peers. While the relative probability of ASD diagnosis among children born LPT was not statistically significant in this limited sample, the results indicate a possible elevated risk. A larger cohort is needed to adequately estimate this risk. PMID- 28989330 TI - Maternal and Neonatal Birth Factors Affecting the Age of ASD Diagnosis. AB - Early diagnosis of autism spectrum disorders (ASD) enables early intervention that improves long term functioning of children with ASD but is often delayed until age of school entry. Few studies have identified factors that affect timely diagnosis. This study addressed how maternal education, race, age, marital status as well as neonatal birth factors affect the age at which a child is diagnosed with ASD. This study involved a retrospective analysis of 664 records of children treated at one of the largest autism treatment centers in the United States from March 1, 2009 to December 30, 2010. Logistic regression and Cox proportional hazards regression were used to identify maternal and neonatal factors associated with age of diagnosis. Infant gender, maternal race, marital status, and maternal age were identified as significant factors for predicting the age of ASD diagnosis. In the Cox proportional hazards regression model, only maternal race and marital status were included. Median survival age till diagnosis of children born to married mothers was 53.4 months compared to 57.8 months and 63.7 months of children born to single and divorced or widowed mothers respectively. Median survival age till diagnosis for children of African American mothers was 53.8 months compared to 57.2 months for children of Caucasian mothers. No statistically significant difference of timing of ASD diagnosis was found for children of varying gestational age. Children born to older or married mothers and mothers of minority races were more likely to have an earlier ASD diagnosis. No statistically significant differences in timing of ASD diagnosis were found for children born at varying gestational ages. Identification of these factors has the potential to inform public health outreach aimed at promoting timely ASD diagnosis. This work could enhance clinical practice for timelier diagnoses of ASD by supporting parents and clinicians around the world in identifying risk factors beyond gender and SES and developing strategies to recognize earlier signs of ASD and contribute to improved development outcomes in children with ASD. PMID- 28989331 TI - mixed messages about teen sex. PMID- 28989332 TI - How do sex ratios in China influence marriage decisions and intra-household resource allocation? AB - This article examines how imbalanced sex ratios influence marriage decisions and household bargaining. Using data from the 1982 Chinese census, the traditional "availability ratio" is modified to reflect the degree to which men tend to marry women from different cohorts. This ratio reflects the average tendency of men to prefer women who are close in age to women who are several years younger than them by weighting cohort sizes using the proportion of people in the population who marry someone born in a different cohort. Given that men generally marry younger women, this ratio varies independently of the size of one's own birth cohort. Yet, the ratio fluctuates considerably across individuals, as the sizes of birth cohorts in China vary across time and regions. This enables us to examine how variability in such ratios may influence marriage decisions and household bargaining. The findings suggest that women exercise greater bargaining power once married. Results indicate that as women become scarcer in the marriage market, they have healthier sons. Men also delay marriage, and consume less tobacco and alcohol. This paper also highlights how sensitive findings may be to using this modified weighted availability ratio rather than a traditional unweighted availability ratio. PMID- 28989333 TI - Nebulized Delivery of the MAPKAP Kinase 2 Peptide Inhibitor MMI-0100 Protects Against Ischemia-Induced Systolic Dysfunction. AB - Acute myocardial infarction (AMI) results in systolic dysfunction, myocarditis and fibrotic remodeling, which causes irreversible pathological remodeling of the heart. Associated cell death and inflammation cause cytokine release, which activates the p38 MAPK signaling pathway to propagate damaging signals via MAPKAP kinase 2 (MK2). Previously we showed that intraperitoneal injection of a cell permeable peptide inhibitor of MK2, MMI-0100, protects against fibrosis, apoptosis and systolic dysfunction in a mouse model of AMI induced by left anterior descending coronary artery (LAD) ligation. Here we tested a new route of administration of MMI-0100: inhalation of nebulized peptide. When given within 30 min of AMI and daily for 2 weeks thereafter, both inhaled and injected MMI-0100 improved cardiac function as measured by conscious echocardiography. Limited fibrosis was observed after 2 weeks by Massons trichrome staining, suggesting that MMI-0100 protects the heart prior to the formation of significant fibrosis. These results support a nebulized route of administration of MMI-0100 can protect the myocardium from ischemic damage. PMID- 28989334 TI - massPix: an R package for annotation and interpretation of mass spectrometry imaging data for lipidomics. AB - INTRODUCTION: Mass spectrometry imaging (MSI) experiments result in complex multi dimensional datasets, which require specialist data analysis tools. OBJECTIVES: We have developed massPix-an R package for analysing and interpreting data from MSI of lipids in tissue. METHODS: massPix produces single ion images, performs multivariate statistics and provides putative lipid annotations based on accurate mass matching against generated lipid libraries. RESULTS: Classification of tissue regions with high spectral similarly can be carried out by principal components analysis (PCA) or k-means clustering. CONCLUSION: massPix is an open source tool for the analysis and statistical interpretation of MSI data, and is particularly useful for lipidomics applications. PMID- 28989335 TI - Estimation of metabolite networks with regard to a specific covariable: applications to plant and human data. AB - INTRODUCTION: In systems biology, where a main goal is acquiring knowledge of biological systems, one of the challenges is inferring biochemical interactions from different molecular entities such as metabolites. In this area, the metabolome possesses a unique place for reflecting "true exposure" by being sensitive to variation coming from genetics, time, and environmental stimuli. While influenced by many different reactions, often the research interest needs to be focused on variation coming from a certain source, i.e. a certain covariable [Formula: see text]. OBJECTIVE: Here, we use network analysis methods to recover a set of metabolite relationships, by finding metabolites sharing a similar relation to [Formula: see text]. Metabolite values are based on information coming from individuals' [Formula: see text] status which might interact with other covariables. METHODS: Alternative to using the original metabolite values, the total information is decomposed by utilizing a linear regression model and the part relevant to [Formula: see text] is further used. For two datasets, two different network estimation methods are considered. The first is weighted gene co-expression network analysis based on correlation coefficients. The second method is graphical LASSO based on partial correlations. RESULTS: We observed that when using the parts related to the specific covariable of interest, resulting estimated networks display higher interconnectedness. Additionally, several groups of biologically associated metabolites (very large density lipoproteins, lipoproteins, etc.) were identified in the human data example. CONCLUSIONS: This work demonstrates how information on the study design can be incorporated to estimate metabolite networks. As a result, sets of interconnected metabolites can be clustered together with respect to their relation to a covariable of interest. PMID- 28989336 TI - Surface-Initiated Polymerization with Poly(n-hexylisocyanate) to Covalently Functionalize Silica Nanoparticles. AB - New methods are needed for covalent functionalization of nanoparticles-surface with organic polymer coronas to generate polymeric nanocomposite in a controlled manner. Here we report the use of a surface-initiated polymerization approach, mediated by titanium (IV) catalysis, to grow poly(n-hexylisocyanate) chains from silica surface. Two pathways were used to generate the interfacing in these nano hybrids. In the first one, the nanoparticles was "seeded" with SiCl4, followed by reaction with 1,6-hexanediol to form hydroxyl groups attached directly to the surface via O-Si-O bonding. In the second pathway, the nanoparticles were initially exposed to a 9:1 mixture of trimethyl silyl chloride and chlorodimethyl octenyl silane which was then followed by hydroboration of the double bonds, to afford hydroxyl groups with a spatially controlled density and surface-attachment via O-Si-C bonding. These functionalized surfaces were then activated with the titanium tetrachloride catalyst. In our approach, thus surface tethered catalyst provided the sites for n-hexyl isocyanate monomer insertion, to "build up" the surface-grown polymer layers from the "bottom-up". A final end-capping, to seal off the chain ends, was done via acetyl chloride. Compounds were characterized by FT-IR, 1H-NMR, GC-MS, GPC, and thermogravimetric analyses. PMID- 28989337 TI - Neuroendocrine Tumor-Targeted Upconversion Nanoparticle-Based Micelles for Simultaneous NIR-Controlled Combination Chemotherapy and Photodynamic Therapy, and Fluorescence Imaging. AB - Although neuroendocrine tumors (NETs) are slow growing, they are frequently metastatic at the time of discovery and no longer amenable to curative surgery, emphasizing the need for the development of other treatments. In this study, multifunctional upconversion nanoparticle (UCNP)-based theranostic micelles are developed for NET-targeted and near-infrared (NIR)-controlled combination chemotherapy and photodynamic therapy (PDT), and bioimaging. The theranostic micelle is formed by individual UCNP functionalized with light-sensitive amphiphilic block copolymers poly(4,5-dimethoxy-2-nitrobenzyl methacrylate) polyethylene glycol (PNBMA-PEG) and Rose Bengal (RB) photosensitizers. A hydrophobic anticancer drug, AB3, is loaded into the micelles. The NIR-activated UCNPs emit multiple luminescence bands, including UV, 540 nm, and 650 nm. The UV peaks overlap with the absorption peak of photocleavable hydrophobic PNBMA segments, triggering a rapid drug release due to the NIR-induced hydrophobic-to hydrophilic transition of the micelle core and thus enabling NIR-controlled chemotherapy. RB molecules are activated via luminescence resonance energy transfer to generate 1O2 for NIR-induced PDT. Meanwhile, the 650 nm emission allows for efficient fluorescence imaging. KE108, a true pansomatostatin nonapeptide, as an NET-targeting ligand, drastically increases the tumoral uptake of the micelles. Intravenously injected AB3-loaded UCNP-based micelles conjugated with RB and KE108-enabling NET-targeted combination chemotherapy and PDT-induce the best antitumor efficacy. PMID- 28989338 TI - Chemical Sensing Systems that Utilize Soft Electronics on Thin Elastomeric Substrates with Open Cellular Designs. AB - A collection of materials and device architectures are introduced for thin, stretchable arrays of ion sensors that mount on open cellular substrates to facilitate solution exchange for use in biointegrated electronics. The results include integration strategies and studies of fundamental characteristics in chemical sensing and mechanical response. The latter involves experimental measurements and theoretical simulations that establish important considerations in the design of low modulus, stretchable properties in cellular substrates, and in the realization of advanced capabilities in spatiotemporal mapping of chemicals' gradients. As the chemical composition of extracellular fluids contains valuable information related to biological function, the concepts introduced here have potential utility across a range of skin- and internal-organ integrated electronics where soft mechanics, fluidic permeability, and advanced chemical sensing capabilities are key requirements. PMID- 28989339 TI - Corrigendum: Clinical and Molecular Heterogeneity of RTEL1 Deficiency. AB - [This corrects the article on p. 449 in vol. 8, PMID: 28507545.]. PMID- 28989340 TI - On the implication of structural zeros as independent variables in regression analysis: applications to alcohol research. AB - In alcohol studies, drinking outcomes such as number of days of any alcohol drinking (DAD) over a period of time do not precisely capture the differences among subjects in a study population of interest. For example, the value of 0 on DAD could mean that the subject was continually abstinent from drinking such as lifetime abstainers or the subject was alcoholic, but happened not to use any alcohol during the period of interest. In statistics, zeros of the first kind are called structural zeros, to distinguish them from the sampling zeros of the second type. As the example indicates, the structural and sampling zeros represent two groups of subjects with quite different psychosocial outcomes. In the literature on alcohol use, although many recent studies have begun to explicitly account for the differences between the two types of zeros in modeling drinking variables as a response, none has acknowledged the implications of the different types of zeros when such modeling drinking variables are used as a predictor. This paper serves as the first attempt to tackle the latter issue and illustrate the importance of disentangling the structural and sampling zeros by using simulated as well as real study data. PMID- 28989341 TI - THE LONG-TERM DYNAMICS OF RACIAL/ETHNIC INEQUALITY IN NEIGHBORHOOD AIR POLLUTION EXPOSURE, 1990-2009. AB - Research examining racial/ethnic disparities in pollution exposure often relies on cross-sectional data. These analyses are largely insensitive to exposure trends and rarely account for broader contextual dynamics. To provide a more comprehensive assessment of racial-environmental inequality over time, we combine the 1990 to 2009 waves of the Panel Study of Income Dynamics (PSID) with spatially- and temporally-resolved measures of nitrogen dioxide (NO2) and particulate matter (PM2.5 and PM10) in respondents' neighborhoods, as well as census data on the characteristics of respondents' metropolitan areas. Results based on multilevel repeated measures models indicate that Blacks and Latinos are, on average, more likely to be exposed to higher levels of NO2, PM2.5, and PM10 than Whites. Despite nationwide declines in levels of pollution over time, racial and ethnic disparities persist and cannot be fully explained by individual , household-, or metropolitan-level factors. PMID- 28989342 TI - Experimental Investigation on Minimum Frame Rate Requirements of High-Speed Videoendoscopy for Clinical Voice Assessment. AB - This study investigated the impact of high-speed videoendoscopy (HSV) frame rates on the assessment of nine clinically-relevant vocal-fold vibratory features. Fourteen adult patients with voice disorder and 14 adult normal controls were recorded using monochromatic rigid HSV at a rate of 16000 frames per second (fps) and spatial resolution of 639*639 pixels. The 16000-fps data were downsampled to 16 other rate denominations. Using paired comparisons design, nine common clinical vibratory features were visually compared between the downsampled and the original images. Three raters reported the thresholds at which: (1) a detectable difference between the two videos was first noticed, and (2) differences between the two videos would result in a change of clinical rating. Results indicated that glottal edge, mucosal wave magnitude and extent, aperiodicity, contact and loss of contact of the vocal folds were the vibratory features most sensitive to frame rate. Of these vibratory features, the glottal edge was selected for further analysis, due to its higher rating reliability, universal prevalence and consistent definition. Rates of 8000 fps were found to be free from visually-perceivable feature degradation, and for rates of 5333 fps, degradation was minimal. For rates of 4000 fps and higher, clinical assessments of glottal edge were not affected. Rates of 2000 fps changed the clinical ratings in over 16% of the samples, which could lead to inaccurate functional assessment. PMID- 28989345 TI - Diary. PMID- 28989346 TI - Competences, conferences and contributions - making the vision a reality. PMID- 28989343 TI - Multifunctional nanoscale strategies for enhancing and monitoring blood vessel regeneration. AB - Nanomedicine has great potential in biomedical applications, and specifically in regenerative medicine and vascular tissue engineering. Designing nanometer-sized therapeutic and diagnostic devices for tissue engineering applications is critical because cells experience and respond to stimuli on this spatial scale. For example, nanoscaffolds, including nanoscalestructured or nanoscale surface modified vascular scaffolds, can influence cell alignment, adhesion, and differentiation to promote better endothelization. Furthermore, nanoscale contrast agents can be extended to the field of biomedical imaging to monitor and track stem cells to better understand the process of neovascularization. In addition, nanoscale systems capable of delivering biomolecules (e.g. peptides and angiogenic genes/proteins) can influence cell behavior, function, and phenotype to promote blood vessel regeneration. This review will focus on nanomedicine and nanoscale strategies applied to vascular tissue engineering. In particular, some of the latest research and potential applications pertaining to nanoscaffolds, biomedical imaging and cell tracking using nanoscale contrast agents, and nanodelivery systems of bioactive molecules applied to blood vessel regeneration will be discussed. In addition, the overlap between these three areas and their synergistic effects will be examined as related to vascular tissue engineering. PMID- 28989347 TI - Infection Prevention 2013 - a potted overview. PMID- 28989344 TI - The Role of Physical Activity Enjoyment on the Acute Mood Experience of Exercise among Smokers with Elevated Depressive Symptoms. AB - PROBLEM: Depressive symptoms are consistently shown to be related to poor smoking cessation outcomes. Aerobic exercise is a potential treatment augmentation that, given its antidepressant and mood enhancing effect, may bolster cessation outcomes for smokers with elevated depressive symptoms. Lower enjoyment of physical activity may inhibit the acute mood enhancing effects of aerobic exercise. The current study investigated the associations between depressive symptoms, physical activity enjoyment and the acute mood experience from exercise among low-active smokers with elevated depressive symptoms. METHOD: Daily smokers with elevated depressive symptoms (N=159; Mage = 45.1, SD = 10.79; 69.8% female) were recruited for a randomized controlled exercise-based smoking cessation trial. Participants self-reported levels of depressive symptoms, physical activity enjoyment, and rated their mood experience (assessed as "mood" and "anxiety") before and after a standardized aerobic exercise test. RESULTS: Hierarchical regression analysis revealed that depressive symptom severity accounted for significant unique variance in physical activity enjoyment (R2 =.041, t = -2.61, p = .010), beyond the non-significant effects of gender and level of tobacco dependence. Additionally, physical activity enjoyment was a significant mediator of the association between depressive symptom severity and acute mood experience ("mood" and "anxiety") following the exercise test. CONCLUSIONS: Physical activity enjoyment may explain, at least in part, how depressive symptom severity is linked to the acute mood experience following a bout of activity. Interventions that target increasing physical activity enjoyment may ultimately assist in enhancing the mood experience from exercise, and therefore improve smoking cessation likelihood, especially for smokers with elevated depressive symptoms. PMID- 28989348 TI - The outcome competency framework for practitioners in infection prevention and control: use of the outcome logic model for evaluation. AB - Healthcare is delivered in a dynamic environment with frequent changes in populations, methods, equipment and settings. Infection prevention and control practitioners (IPCPs) must ensure that they are competent in addressing the challenges they face and are equipped to develop infection prevention and control (IPC) services in line with a changing world of healthcare provision. A multifaceted Framework was developed to assist IPCPs to enhance competence at an individual, team and organisational level to enable quality performance and improved quality of care. However, if these aspirations are to be met, it is vital that competency frameworks are fit for purpose or they risk being ignored. The aim of this unique study was to evaluate short and medium term outcomes as set out in the Outcome Logic Model to assist with the evaluation of the impact and success of the Framework. This study found that while the Framework is being used effectively in some areas, it is not being used as much or in the ways that were anticipated. The findings will enable future work on revision, communication and dissemination, and will provide intelligence to those initiating education and training in the utilisation of the competences. PMID- 28989349 TI - An exploration of NHS staff views on tuberculosis service delivery in Scottish NHS boards. AB - Tuberculosis (TB) is a bacterial disease and major worldwide killer with an increased UK incidence rate. This study aimed to explore the views of National Health Service (NHS) staff on TB service delivery models of care in NHS boards across Scotland. Eighteen semi-structured interviews were conducted with 13 nurse specialists and five consultants in public health medicine (CPHM) across five Scottish NHS boards. Five main themes emerged and findings showed that: directly observed treatment (DOT) was provided only to patients assessed to be at high risk of poor treatment adherence; contact tracing was conducted by participating NHS boards but screening at ports was thought to be weak; all NHS boards implemented TB awareness campaigns for TB health professionals; three NHS boards conducted team meetings that monitored TB patient progress; participants believed that TB funding should be increased; contact tracing was routinely conducted by TB nurses. Improved TB screening at airports was recommended and a need for TB health education for high risk groups was identified. PMID- 28989351 TI - Outbreak Column 12: Nosocomial Staphylococcus aureus outbreaks (part 1). PMID- 28989353 TI - Diary. PMID- 28989350 TI - Can measuring environmental cleanliness using ATP aid in the monitoring of wards with periods of increased incidence of Clostridium difficile? AB - Management of periods of increased incidence of Clostridium difficile (PIIs) on a ward have become multi-factorial and involve isolation of patients, typing of the isolates, antibiotic audit and a weekly environmental audit completed until three consecutive weekly passes are obtained. The aim of this study was to establish if monitoring the environment using adenosine triphosphate (ATP) could aid in reducing the length of time the wards remained on the weekly environmental audit. Secondly, it was to establish if certain pieces of equipment had continually high ATP scores requiring wider interventions. The study took place across three hospital sites covered by one infection control team over a 22 month period. There were three study periods, with the only difference being that ATP monitoring was conducted during period B. There was a difference in the length of time the wards remained on the audit between the first period and the ATP period; however this decrease was sustained in the third period when ATP monitoring ceased. There was an increase in the percentage of sites achieving a pass with ATP week on week. ATP monitoring provided the staff with non-subjective results and immediate feedback that facilitated discussions about cleaning regimes. ATP monitoring was a useful adjunct to environmental audits. PMID- 28989354 TI - Doing the right things well. PMID- 28989355 TI - Screening haematology patients for carbapenem-resistant Klebsiella pneumoniae. AB - Following a cluster of haematology patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) septicaemia, we initiated screening for rectal carriage of CRKP and multidrug-resistant K. pneumoniae (MDRKP) in this patient group. Haematology inpatients submit a rectal swab once weekly. When plated onto chromogenic BrillianceTM UTI Agar (Oxoid), and incubated overnight with a 10 ug ertapenem disc (Oxoid), K. pneumoniae is identified and semi-automated antibiotic susceptibility testing is performed using the Vitek 2 analyser (Biomerieux). When no zone of inhibition occurs, immediate intervention through patient isolation and enhanced environmental cleaning can be instigated to control further spread while empirical antibiotic prescribing is adapted to take account of identified resistances. Over 2 years, six patients with CRKP and 20 patients with MDRKP were identified. These isolates were resistant to first-line empirical treatment choices for neutropenic sepsis and presented a clinical risk of treatment failure for sepsis post cytotoxic chemotherapy. We describe how this rectal screening methodology was developed and how the results influenced appropriate antibiotic prescribing, patient placement in single rooms and the cleaning of the ward environment to prevent person-to-person transmission of MDRKP and CRKP. PMID- 28989356 TI - Knowledge regarding assessment of sepsis among Greek nurses. AB - The aim of the present survey was to evaluate nurses' knowledge regarding sepsis in Greece. A total of 835 registered nurses (125 males/710 females) from tertiary hospitals in Greece were interviewed from April 2008 to December 2009. All participants completed a self-completed questionnaire about assessment of sepsis (see Figure 1). Basic demographic information was recorded. The protocol and questionnaire were approved by the Ethics Committees of participating hospitals. The majority of the participants answered correctly regarding awareness of systemic inflammation - 83.5% regarding the role of temperature in the definition of systemic inflammation; 81.3% regarding the importance of white blood cell count; and 49.9% and 46.3% regarding the role of tachycardia and tachypnoea, respectively. The same pattern was observed regarding the answers about the assessment of sepsis - 79.4% of the nurses answered correctly about the role of blood pressure; 70.9% about the role of urine volume; and 43.5% about the importance of oxygen saturation. Finally, 57.2% of the participants confirmed that in practice they followed the current guidelines for the diagnosis and treatment of patients with sepsis. The study has established baseline data with which future studies can be compared. PMID- 28989357 TI - Infection prevention and control self-audit: just a tick box exercise? AB - The National Health Service (NHS) in England continues to experience ongoing change in order to complete the transition to the new delivery system outlined in Liberating the NHS (Department of Health, 2010a). Treating and caring for patients in a safe environment and protecting them from acquiring avoidable infections remains a high priority and a central quality improvement component within the outcome Indicator set for 2013/14 (NHS Commissioning Board, 2012a). Infection prevention and control practitioners will be required to use a range of innovative quality improvement strategies to facilitate engagement with clinicians and meet the challenges that lie ahead for the NHS. The purpose of this paper is to report on the implementation of an infection prevention and control self-audit (IPCSA) project within general practice. The aim of the project was to empower practice staff to become actively involved with an infection prevention and control (IPC) audit in order to support the development of an IPC quality improvement culture within general practice teams. The paper outlines the methodology used to implement self-audit. The findings suggest that IPCSA can be used as an effective alternative to an IPC nurse-led infection prevention and control audit. PMID- 28989358 TI - Outbreak Column 13: Nosocomial Staphylococcus aureus outbreaks (part 2 - guidelines). PMID- 28989360 TI - Guest Editorial. PMID- 28989361 TI - Diary. PMID- 28989362 TI - A personal experience of care and the lack of it. PMID- 28989363 TI - Patient perspective: is hand hygiene really the most important thing we do? PMID- 28989364 TI - Implementation of a patient-held urinary catheter passport to improve catheter management, by prompting for early removal and enhancing patient compliance. AB - Over the past few years a number of strategic initiatives to improve catheter management and reduce associated infections have been introduced. This paper details the introduction of a patient-held catheter passport and an improved documentation record using the PDSA (Plan, Do, Study, Act) cycle of change implementation in one large acute National Health Service (NHS) trust and local health economy (NHS Institute for Innovation and Improvement, 2008). PMID- 28989365 TI - Educational innovation for infection control in Tanzania: bridging the policy to practice gap. AB - The incidence of hospital acquired infection in developing countries is between two to 20 times higher than in developed countries and is attributable to multiple causes. Evidence-based international policies and guidelines developed to improve infection prevention and control are often not used in practice in these countries. To combat this challenge, this article presents an innovative educational framework used to bridge the gap between policy written by global health agencies and the realities of practice in Tanzania. PMID- 28989366 TI - Do ward and department managers know their responsibilities in relation to the management of sharps, and is this reflected in the way that they practise sharps management? AB - Needlestick injuries (NSIs) involving hollowbore needles are the most commonly reported occupational exposure within the healthcare sector in the United Kingdom (HPA, 2012). It is estimated that at least 100,000 NSIs occur each year but due to under-reporting the figure may be much higher (RCN, 2008). Many strategies aimed at preventing NSIs have been implemented in the healthcare environment, including administrative controls, safer work practices and engineering controls, but despite these measures NSIs remain a serious health and safety threat (EU, 2010). New legislation has now been introduced as part of EU Directive 2010/32/EU, which requires UK and all EU member states to bring into force regulations, laws and administrative provisions to further protect healthcare workers from sustaining NSIs (EU Directive, 2010). The aim of this study was to determine the degree of responsibility that NHS ward/department managers felt they have in relation to the prevention and management of NSIs and if this was reflected in the way that they carry out relevant practices in their clinical environment. The study also aimed to identify factors which might impact on the ward/department managers' ability to manage sharps effectively. The study found that although ward/department managers did acknowledge a high degree of responsibility overall for the prevention and management of NSIs, there were some concerns highlighted in relation to certain practices. These included not ensuring that all staff had received up to date training on the safe use and disposal of sharps and not disseminating information on NSI incidences and outcomes to staff in their clinical areas. The findings of this study have the potential to inform and enhance future training and education schedules that relate to NSI prevention and management and to improve the corporate strategic commitment to reducing NSIs across healthcare organisations. PMID- 28989369 TI - Diary. PMID- 28989367 TI - Identification and control of a gentamicin resistant, meticillin susceptible Staphylococcus aureus outbreak on a neonatal unit. AB - We describe the identification and control of an outbreak of gentamicin resistant, meticillin susceptible Staphylococcus aureus (GR-MSSA) on a 36-bed neonatal unit (NNU) in London. Control measures included admission and weekly screening for GR-MSSA, cohorting affected babies, environmental and staff screening, hydrogen peroxide vapour (HPV) for terminal disinfection of cohort rooms, and reinforcement of hand hygiene. Seventeen babies were affected by the outbreak strain over ten months; seven were infected and ten were asymptomatic carriers. The outbreak strain was gentamicin resistant and all isolates were indistinguishable by pulsed-field gel electrophoresis. The outbreak strains spread rapidly and were associated with a high rate of bacteraemia (35% of 17 affected patients had bacteraemia vs. 10% of 284 patients with MSSA prior to the outbreak, p=0.007). None of 113 staff members tested were colonised with GR-MSSA. GR-MSSA was recovered from 11.5% of 87 environmental surfaces in cohort rooms, 7.1% of 28 communal surfaces and 4.1% of 74 surfaces after conventional terminal disinfection. None of 64 surfaces sampled after HPV decontamination yielded GR MSSA. Recovery of GR-MSSA from two high level sites suggested that the organism could have been transmitted via air. Occasional breakdown in hand hygiene compliance and contaminated environmental surfaces probably contributed to transmission. PMID- 28989370 TI - Editorial: From evidence into practice. PMID- 28989372 TI - Implementing a ward accreditation programme to drive improvements in infection prevention. AB - University Hospitals Southampton NHS Foundation Trust aspires to be a national leader in the reduction of healthcare associated infections (HCAIs). The need to further improve patient safety requires continual improvements in infection control practice in order to sustain high quality and safe patient care. To help achieve this, an infection prevention ward accreditation scheme was introduced across the trust in 2009. The accreditation scheme was initially based on the results of clinical wards'/areas' infection prevention audits, aiming to motivate wards to achieve success and support areas to identify and address gaps in compliance. The ward accreditation scheme acts as a certification of best practice and policy compliance related to reducing HCAIs. Since its introduction four years ago, the ward accreditation programme has been expanded and developed to incorporate other elements of infection prevention policy and practice and continues to be developed in order to drive the trust forward as leaders in infection prevention. The introduction and ongoing development of the accreditation scheme has encouraged healthy competition, aiding local ownership and driving forward improvements, and with this, the trust has significantly reduced infection rates over the last four years. PMID- 28989371 TI - Point prevalence survey of urinary catheterisation in care homes and where they were inserted, 2012. AB - The extent to which the use of catheter care bundles and other interventions has led to a reduction in urinary catheterisation rates is unknown. We aimed to determine current urinary catheterisation rates in care homes with residents over 65 years old, and determine the extent to which residents are discharged from the hospital setting with urinary catheters. A point prevalence questionnaire survey was used in care homes that looked after residents over 65 years in six UK health boards or primary care trusts, to determine urinary catheterisation rates, and where these catheters were inserted. Questionnaires for 445 of 461 care homes (96.5%) were completed, 425 of 445 care homes cared for residents over 65 years; 888 (6.9%) of 12,827 residents had a urethral (82.5%) or supra-pubic (17.5%) urinary catheter. Over half of all catheters (both urethral and suprapubic, 57.4%, 509 of 888 catheters), and 3.1% of all residents had a catheter inserted while the residents were hospital inpatients, and then discharged back to the care home still catheterised. There was a significant variation in urinary catheterisation rates in the care homes surveyed, and rates remain similar to previous English surveys in 2003 and 2009. More still needs to be done to understand the variation in urinary catheterisation rates in care homes and reduce these rates, including the numbers of residents that are discharged from hospital with a urinary catheter. PMID- 28989373 TI - Physical space and its impact on waste management in the neonatal care setting. AB - This paper reports an investigation intended to obtain some understanding of how the working environment might influence the practice and knowledge of those involved in the management of healthcare waste. The National Health Service (NHS) has a continuing waste problem, and the way it manages waste harms the environment and consumes resources. It has been estimated that the carbon footprint of the NHS in England is approximately 20 million tons of CO2e. It has been suggested that better waste segregation could lead to more effective recycling, saving up to 42,000 tonnes of CO2. This qualitative study employed non participant observation and semi-structured interviews. The interviews were carried out with the key informants within the participating neonatal intensive care unit. Findings from this study indicate that space and the physical arrangement of the environment are significant and influential factors in clinical practice. Where the clinical environment is not supportive, poor infection control and waste management practice is likely to occur. However, proximity of staff caused by a lack of physical space might facilitate situated learning and a collective development of knowledge in practice. The implementation of sustainable waste management practices would be more likely to succeed in an environment that facilitates correct waste segregation. PMID- 28989374 TI - Impact of a central venous line care bundle on rates of central line associated blood stream infection (CLABSI) in hospitalised children. AB - Central line associated bloodstream infection (CLABSI) reduction programmes in hospitalised children have been focused in the intensive care setting and little data is available on the efficacy and cost effectiveness of such programmes in other clinical areas. Prospective monitoring of hospital acquired CLABSI rates in all clinical areas was performed at Alder Hey Children's Hospital for a period of three years following the implementation of a central venous line (CVL) care bundle. We observed a decrease in CLABSI rates from 220 in the first year following intervention to 108 per 100,000 patient days (p=0.002) in the third year of the study, demonstrating a decrease of over 50% in CLABSI rates. Blood culture contamination rates were also significantly reduced. The introduction of a CVL care bundle produced a significant, sustainable reduction in hospital acquired CLABSI rates in a children's hospital setting. PMID- 28989375 TI - An observational study of hand hygiene adherence following the introduction of an education intervention. AB - Hand hygiene adherence needs to be increased and sustained in order to prevent and reduce healthcare associated infections. We implemented an educational intervention and observed the adherence of healthcare workers, patients and visitors over 24 hour periods at four observation points. For healthcare workers a total of 2,294 opportunities were observed and for patients and visitors, a total of 597 opportunities were observed. Healthcare worker adherence increased following the introduction of the educational intervention, with 53.0% (282/532) adherence at baseline (observation point 1), and was sustained varying between 67.7% and 70.8% in the post-intervention points (p=0.0007). The greatest increase in adherence was observed between baseline and the observation point 2. Adherence varied according to type of opportunity (p<0.0001) with the lowest level of adherence observed after contact with patient surroundings, however there was no obvious trend across the observation points. There was an interaction between point of study and ward (p=0.0001). For patients and visitors, adherence did differ according to the point of study (p=0.0074) with adherence prior to the intervention being 49.1% and then ranging from 43.5-61.8%. We suggest that future educational interventions should be implemented as this study implies that there is potential for increased and sustained adherence to hand hygiene protocols. PMID- 28989376 TI - Outbreak column 14: Staphylococcus aureus - new outbreaks of old infections. PMID- 28989378 TI - Diary. PMID- 28989379 TI - Sepsis and the impact of life-threatening infection - working together to make an impact. PMID- 28989380 TI - Are your IPC policies fit for purpose? AB - Infection prevention and control practitioners are well versed in protecting patients from harm. Recent political, public and media attention about unsafe organisations has brought doubts into many minds as to the safety of our healthcare services. Infection prevention and control policies are the mainstay in ensuring compliance with best evidence-based practices, but with many mergers of community and secondary care infection prevention and control teams, policies have to be reviewed and revised to ensure they meet both organisational and patient/employer safety needs. This paper reflects contemporary literature around policy development. It will discuss how to develop, implement and evaluate comprehensive policies that will fit the needs of organisations while protecting their population of employees and patients. PMID- 28989381 TI - Sharps injury reduction: a six-year, three-phase study comparing use of a small patient-room sharps disposal container with a larger engineered container. AB - A 350-bed Sydney hospital noted excessive container-associated sharps injuries (CASI) using small sharps containers and compared the effect from 2004 to 2010 of using a larger container engineered to reduce CASI. In Phase 1 (Ph1), disposable 1.4L containers (BD Australia) were carried to/from patients' rooms. In Phase 2 (Ph2), this stopped and a safety-engineered 32L reusable container (the Device; Sharpsmart, SteriHealth) was mounted in medication stations only and sharps were carried to and from patient rooms using kidney dishes. In Phase 3 (Ph3), the Device was wall-mounted in patient rooms. Sharps injuries were categorised as 'during-procedure', 'after-procedure but before disposal', 'CASI', and 'improper disposal SI'. Disposal-related SI comprised CASI plus improper-disposal SI. Injuries per 100 full-time-equivalent staff were analysed using Chi2; p <= 0.05; and relative risk and 95% confidence limits were calculated. In Ph1 (small containers) 19.4% of SI were CASI and transport injuries were zero. In Ph2 (Device in medication station) CASI fell 94.9% (p <0.001); Disposal-related SI fell 71.1% (p=0.002) but transport injuries rose significantly. In Ph3 (Device in patient room) zero CASI occurred (p<0.001); Disposal-related SI fell 83.1% (p=0.001). Recapping SI fell 85.1% (p=0.01) with the Device. The Device's volume, large aperture, passive overfill-protection and close-at-hand siting are postulated as SI reduction factors. PMID- 28989382 TI - An audit of neonatal and infant hepatitis B immunisation and serological testing in two counties of England, 2007-12. AB - We audited adherence to national hepatitis B virus (HBV) immunisation policy for neonates and infants born to HBV positive mothers in two counties of England during 2007/08 to 2011/12 (n=112 in County X, n=190 in County Y). Over the five year period, 29.9% of at risk neonates in County X and 23.5% in County Y required hepatitis B immunoglobulin (HBIG) at birth. The annual median age of HBIG administration was 0.0-0.5 days. The annual median coverage and timeliness of the first (coverage range 92.3-100.0%; age of administration range 0.0-0.0 days), second (83.8-100.0%; 32.0-42.0 days), third (81.1-100.0%; 62.0-81.0 days) and fourth dose HBV immunisations (44.4-91.9%; 378.0-443.0 days) and serological testing (8.6-81.0%; 450.0-707.0 days) were calculated. Statistically significant variation was found in the coverage of third and fourth dose immunisations in County Y, age of fourth dose immunisation in County X, and the coverage and timeliness of serological testing in both counties (p < 0.05). HBIG and the first three HBV immunisations were commonly administered according to the national schedule. Fourth dose immunisations and serological tests showed poor adherence. We advocate public health interventions to improve immunisation programme outcomes and hepatitis B surface antigen testing. PMID- 28989383 TI - A pilot observational study of hydrogen peroxide and alcohol for disinfection of privacy curtains contaminated by MRSA, VRE and Clostridium difficile. AB - Privacy curtains, frequently used in hospitals to separate patient care areas may have an important role in the transmission of healthcare-associated pathogens. In this pilot study, we inoculated curtain swatches with suspensions of clinical specimens of meticillin resistant Staphylococcus aureus (MRSA), vancomycin resistant enterococcus (VRE), and Clostridium difficile before using a gloved hand to touch the inoculated curtain swatch and transfer to clean agar plates. Three different commonly used disinfectants were then sprayed onto these swatches before using a clean gloved hand to touch the swatch and transfer onto new agar plates. All plates were incubated at 35 degrees C for 24 and 72 h. Bacterial growth before and after disinfection was assessed and compared. 3.1% hydrogen peroxide effectively eliminated transfer of C. difficile, MRSA and VRE from inoculated curtains. PMID- 28989386 TI - Diary. PMID- 28989387 TI - Antibiotic Guardianship. PMID- 28989384 TI - Outbreak Column 15: Carbapenemase-producing Enterobacteriaceae. PMID- 28989388 TI - Review of technologies available to improve hand hygiene compliance - are they fit for purpose? AB - Hand hygiene has been empirically proven to prevent cross-transmission of infection, which has led to the development of global guidelines such as the World Health Organization's 'My 5 Moments for Hand Hygiene.' Because of the relatively recent launch of these guidelines (2009) technology designed to assist in measuring hand hygiene compliance appears not to fully acknowledge the influence of the WHO 5 Moments for hand hygiene Consequently, they may not be fit for purpose (FFP). This paper uses a review of the literature on current hand hygiene technology to assess the extent to which these are FFP based on these global guidelines. The results show that there are a variety of technologies available to assist with the monitoring and measurement of hand hygiene levels. However, none appear to explicitly achieve detection of all WHO 5 Moments for hand hygiene, limiting their effectiveness. The authors conclude that a systems approach offers a potential aid for developers aspiring to meet domain specific FFP requirements. Human factors may help guide such developments to meet user and context specific needs. PMID- 28989389 TI - Vaccine-preventable disease susceptibility in a British paediatric assessment unit. AB - Aims: To evaluate practice within a paediatric secondary-care centre before and after introduction of simple interventions to improve identification of under immunised children and facilitate catch-up immunisations. Methods: The population based child health database was used to check immunisation status for two cohorts of 200 consecutive admissions before and after routine printing of immunisation histories from the database and raising staff awareness. Vaccine-preventable disease (VPD) susceptibility burdens were calculated for each child. Case notes were assessed for accuracy and documentation of ward-based interventions. Results: Fourteen per cent of all children were under-immunised on admission and 27% of these were more than five years behind schedule. Under-immunised children's VPD susceptibility burdens ranged from 0-40,858 days and in 59% exceeded 1,000 days. Over one month the paediatric admission unit saw children with a combined VPD susceptibility burden of 1,323 child-years. Positive identification of under-immunised children increased by 40% (95% confidence interval: 12-62, p=0.002) following the introduction of routine database printouts. Conclusion: Children presenting to British secondary care units have large VPD susceptibility burdens. Positive identification of under-immunised children substantially improved after the introduction of routine database printouts, but catch-up immunisation rates did not increase. PMID- 28989390 TI - The antibacterial effect of 2-octyl cyanoacrylate (Dermabond(r)) skin adhesive. AB - Dermabond(r) is a tissue adhesive commonly used for wound or surgical incision closure. Its use has previously been associated with a reduction in wound infection, and it has been thought to act as a physical barrier to bacteria accessing the wound. This study aimed to establish whether the Dermabond(r) adhesive demonstrated any intrinsic antimicrobial properties. Solidified pellets of Dermabond(r) were placed on standardised Agar plates cultured with a variety of pathogens. Inhibition of growth was demonstrated against Gram-positive bacteria. Culture swabs taken from the inhibition rings demonstrated no growth, suggesting that Dermabond has a bactericidal mechanism of action. Based on the design of this study, the results suggest that Dermabond(r) demonstrates bactericidal properties against Gram-positive bacteria. Its use for wound closure following surgical intervention may reduce postoperative wound infection by Gram positive organisms. PMID- 28989392 TI - Informing the practice of infection prevention and control. PMID- 28989393 TI - Adenosine triphosphate bioluminescence assay for monitoring contamination of the working environment of anaesthetists and cleanliness of the operating room. AB - Anaesthetists possibly contribute to the spread of infections during anaesthesia. The adenosine triphosphate (ATP) bioluminescence assay is an easy-to-perform, on the-spot assay that provides objective data; therefore, using the LuciPac(r)Pen and the Lumitester PD-20(r)System, we assessed contamination of the working environment of anaesthetists before and after surgery as well as their hands at the time of each procedure during induction and extubation. Similarly, cleanliness of the operating room was evaluated using this assay to determine whether it is useful to assess the effectiveness of the routine cleaning protocols followed after surgery. ATP concentrations in the working environment of anaesthetists and their hands increased during surgery. In addition, ATP concentrations within the working environment decreased after routine cleaning with ethanol or accelerated hydrogen peroxide; however, there were no differences in the number of sites with ATP concentrations >500 relative light units before and after cleaning. This method is useful to evaluate contamination of the working environment of anaesthetists; nevertheless, it is prudent to evaluate the effectiveness of routine cleaning protocols because ATP bioluminescence assays are influenced by the use of various disinfectants at varying concentrations. PMID- 28989394 TI - Knowledge, attitude and practice of standard precautions of infection control by hospital workers in two tertiary hospitals in Nigeria. AB - BACKGROUND: Standard precautions are recommended to prevent transmission of infection in hospitals. However, their implementation is dependent on the knowledge and attitudes of healthcare workers (HCW). This study describes the knowledge, attitude and practice (KAP) of standard precautions of infection control among HCW of two tertiary hospitals in Nigeria is described. METHODS: A cross-sectional study was undertaken in 2011/2012 among HCW in two tertiary hospitals in Nigeria. Data was collected via a structured self-administered questionnaire assessing core elements of KAP of standard precautions. Percentage KAP scores were calculated and professional differences in median percentage KAP scores were ascertained. RESULTS: A total of 290 HCW participated in the study (76% response rate), including 111 (38.3%) doctors, 147 (50.7%) nurses and 32 (11%) laboratory scientists. Overall median knowledge and attitude scores toward standard precautions were above 90%, but median practice score was 50.8%. The majority of the HCW had poor knowledge of injection safety and complained of inadequate resources to practise standard precautions. House officers, laboratory scientists and junior cadres of nurses had lower knowledge and compliance with standard precautions than more experienced doctors and nurses. CONCLUSION: Our results suggest generally poor compliance with standard precautions of infection control among HCW in Nigeria. Policies that foster training of HCW in standard precautions and guarantee regular provision of infection control and prevention resources in health facilities are required in Nigeria. PMID- 28989395 TI - The misuse and overuse of non-sterile gloves: application of an audit tool to define the problem. AB - BACKGROUND: The use of non-sterile gloves (NSG) has become routine in the delivery of health care, often for procedures for which they are not required; their use may increase the risk of cross contamination and is generally not integrated into hand hygiene audit. This paper describes a small-scale application and validation of an observational audit tool devised to identify inappropriate use of NSG and potential for cross contamination. METHODS: Two observers simultaneously observed the use of NSG during episodes of care in an acute hospital setting. The inter-rater reliability (IRR) of the audit tool was measured corrected for chance agreement using Kappa. RESULTS: A total of 22 episodes of care using NSG were observed. In 68.6% (24/35) of procedures there was no contact with blood/body fluid; in 54.3% (19/35) NSG-use was inappropriate. The IRR was 100% for eight of 12 components of the tool. For hand hygiene before and after NSG removal it was 82% (Kappa = 0.72) and 95% (Kappa = 0.87). CONCLUSIONS: In this small-scale application of a glove-use audit tool we demonstrated over-use and misuse of NSG and potential for cross transmission on gloved hands. The audit tool provides an effective mechanism for integrating glove use into the audit of hand hygiene behaviour. PMID- 28989396 TI - Outbreak Column 16: Cognitive errors in outbreak decision making. AB - During outbreaks, decisions must be made without all the required information. People, including infection prevention and control teams (IPCTs), who have to make decisions during uncertainty use heuristics to fill the missing data gaps. Heuristics are mental model short cuts that by-and-large enable us to make good decisions quickly. However, these heuristics contain biases and effects that at times lead to cognitive (thinking) errors. These cognitive errors are not made to deliberately misrepresent any given situation; we are subject to heuristic biases when we are trying to perform optimally. The science of decision making is large; there are over 100 different biases recognised and described. Outbreak Column 16 discusses and relates these heuristics and biases to decision making during outbreak prevention, preparedness and management. Insights as to how we might recognise and avoid them are offered. PMID- 28989398 TI - Clostridium difficile period of increased incidence in hospitals. PMID- 28989400 TI - IPS Spotlight. PMID- 28989399 TI - Reply to 'Clostridium difficile period of increased incidence in hospitals'. PMID- 28989401 TI - Diary. PMID- 28989402 TI - Achieving best practice in infection prevention: evidence from the real world. PMID- 28989403 TI - Infection control intervention on meticillin resistant Staphylococcus aureus transmission in residential care homes for the elderly. AB - BACKGROUND: The objectives were to evaluate the effectiveness of an infection control bundle in controlling the meticillin resistant Staphylococcus aureus (MRSA) transmission in residential care homes for the elderly (RCHEs) in Hong Kong. METHODS: This was a two-arm cluster randomised controlled trial. Infection control bundles focused on hand hygiene (HH), environmental hygiene, and modified contact precautions were applied to the intervention arm. Nasal swabs from residents; staff HH compliance and effectiveness; and environmental hygiene were assessed by microbiological sampling or observation at the baseline and quarterly after the intervention. RESULTS: A total of 2776 residents from 36 RCHEs were recruited. The overall MRSA prevalence was 20.4% (95% confidence interval, 18.9% 21.9%). The intervention elicited an immediate effect of 2.4% absolute decrease in the prevalence and 3.7% in the intra-facility transmission, though the difference between the two arms was insignificant. Staff HH compliance increased substantially from 5.9% to 45.6% post-intervention (p < 0.001). CONCLUSIONS: We initiated the infection control culture into the RCHEs and gained their acceptance. However, this behavioural change takes time to emerge. Our study shows that relying on the bundle alone could not bring sustainable MRSA reduction. Administrative control for strengthening infection control infrastructure is important for continuous compliance and improvement. PMID- 28989404 TI - Examining the policies and guidelines around the use of masks and respirators by healthcare workers in China, Pakistan and Vietnam. AB - BACKGROUND: There is an ongoing debate regarding the type of respiratory protection that should be recommended for use for healthcare workers. MATERIALS AND METHODS: A cross-sectional survey was conducted in three countries: China, Pakistan and Vietnam. RESULTS: In China and Pakistan, the infection control guidelines were developed to be in line with the recommendations from the World Health Organization (WHO) and the Centers for Disease Control and Prevention, while in the Vietnamese guidelines the recommendations correspond with the WHO suggestions only. The guidelines from all three countries document the need for training and fit testing; however there is no system to monitor the training and fit testing programs. Across the three countries, there was some inconsistency with regard to the types of products (i.e. masks vs. respirators) recommended for influenza, severe acute respiratory syndrome (SARS) and tuberculosis. CONCLUSIONS: Available evidence should be examined and a comprehensive policy should be developed on the use of masks and respirators. The policy should address critical areas such as regulation, training, fit testing and reuse. PMID- 28989405 TI - The effect of different oral hygiene treatments on the occurrence of ventilator associated pneumonia (VAP) in ventilated patients. AB - BACKGROUND: We compared the incidence of ventilator associated pneumonia (VAP) among patients treated with comprehensive oral care to those treated with conventional methods of oral care. METHODS: We conducted a prospective, controlled study in an intensive care unit of 90 ventilated patients. Patients in the study group received a comprehensive oral hygiene treatment regimen that involved tooth brushing, suctioning, sodium bicarbonate, rinsing with an antiseptic solution containing 1.5% hydrogen peroxide and a mouth moisturiser. Patients in the control group received a more conventional treatment that included cleaning with a sponge and atraumatic clamp, and rinsing with a 0.2% solution of chlorhexidine gluconate. RESULTS: Among the 90 patients admitted to the ICU, 8.9% of the study group developed VAP compared with 33.3% of the control group (p< 0.004). The development of VAP per 1,000 ventilation days was 10.2 in the study group, and 29.5 in the control group (p< 0.06). The mean number of ventilation days and the mean number of hospitalisation days were also lower in the study group. CONCLUSIONS: In patients who are ventilated, a comprehensive oral hygiene treatment regimen that includes tooth brushing, suctioning and rinsing with an antiseptic is more effective in preventing VAP than more conventional protocols. PMID- 28989406 TI - The effect of a quality improvement programme reducing blood culture contamination on the detection of bloodstream infection in an emergency department. AB - BACKGROUND: Contaminated blood cultures (BC) generate avoidable costs and prolong hospital stays. To measure our hospital's performance against the recommended standard of <3% BC contamination, we performed a prospective study. METHODS: We prospectively determined the frequency of contaminated and genuinely positive BC hospital-wide over seven months. RESULTS: Overall, 73 of 1,829 blood cultures reviewed were contaminated (4.0%). However, distribution of contamination was not uniform. Finding a consistently higher incidence of contamination (11.7%) in our emergency department (ED) than elsewhere in the hospital (2.5%), we adopted a collaborative quality improvement strategy targeted to the ED. A combination of education, modified BC packs and regular feedback of BC results was associated with a significant reduction in contamination (7.4%, p=0.01) over the next six months. Our data suggests that contaminated BC were more likely to have been taken during regular day time hours (odds ratio (OR) 2.7, p=0.012), rather than overnight and were not associated with influxes of new junior medical staff. We found no evidence that the incidence of true bloodstream infection (12.8%) diagnosed by our ED was adversely affected by our intervention (10.7%, p=0.35). CONCLUSIONS: Using a simple and inexpensive collaborative intervention we reduced BC contamination without adversely affecting the detection of genuine BSI. PMID- 28989407 TI - Non-food environmental exposure to Escherichia coli O157:H7 - the risks of cycling on muddy pathways. PMID- 28989410 TI - Diary. PMID- 28989409 TI - IPS Spotlight. PMID- 28989411 TI - Collaboration in the prevention of surgical site infection: the OneTogether project. PMID- 28989412 TI - Epidemiology and outcomes of Stenotrophomonas maltophilia and Burkholderia cepacia infections among trauma patients of India: a five year experience. AB - BACKGROUND: Infections by uncommon non-fermenting Gram negative bacteria are on the rise, but little is known about the risk factors and drug resistance in trauma patients in India. This study explored the infections caused by Stenotrophomonas maltophilia and/or Burkholderia cepacia in trauma patients over a period of 5 years. MATERIAL AND METHODS: Patients admitted for trauma care with S. maltophilia and/or B. cepacia isolated from clinical specimens were enrolled. Characteristics regarding the strain isolation, drug sensitivity pattern, multidrug resistance (MDR), patient, outcomes, and differentiation of true infection from colonisation were observed. RESULTS: Of the total 233 isolates, 102 were S. maltophilia and 131 were B. cepacia; 4.3% were responsible for polymicrobial infections with other bacteria. There were more B. cepacia MDR isolates than S. maltophilia. Maximum resistance was found to tetracycline (86.7%) and tobramycin (86.7%) in B. cepacia and to co-trimoxazole (68.7%) in S. maltophilia. Of these, 21 (16.03%) had a fatal outcome and the remaining 111 (84.7%) were discharged healthy. The in-hospital mortality rate associated with B. cepacia was much (16%) higher than S. maltophilia (13%) at this centre. CONCLUSION: The analysis of epidemiology and outcome of these infections will help to inform their management and treatment. PMID- 28989413 TI - Percutaneous endoscopic gastrostomy (PEG) site infections: a clinical and microbiological study from university teaching hospital, India. AB - BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is used to provide enteral access in patients who are unable to swallow. Infection of the stoma is an important complication and there is little data from India on this problem, which can be used to inform infection prevention and prophylactic strategies. AIM: The objective was to assess the prevalence and the role of contributory factors in PEG site infections. METHODS: A total of 173 patients underwent PEG insertion from January 2011 to May 2012. Clinical and microbiological data were collected for culture-positive cases. Insertion was performed using a standard sterile pull through technique. Infections were defined as two of: peristomal erythema, induration, and purulent discharge. RESULTS: A total of 54 PEG infections occurred in 43 patients (28.85%). Seventy-seven organisms were isolated. Pseudomonas aeruginosa was the most common (n=29) followed by coliforms (n=21) and meticillin resistant Staphylococcus aureus (MRSA) (n=6). Thirty-one (72%) received amoxicillin-clavulanic acid as prophylaxis and 12 (28%) were receiving concomitant antibiotics for their underlying conditions. The occurrence of PEG site infections was statistically independent of the administered prophylactic antibiotics (p=0.3). CONCLUSIONS: This study has demonstrated the importance of PEG sites as a cause of healthcare associated infections. Educating patients on wound care practices would play a significant role in prevention of PEG site infections. PMID- 28989414 TI - The OneTogether collaborative approach to reduce the risk of surgical site infection: identifying the challenges to assuring best practice. AB - BACKGROUND: Surgical site infections (SSI) account for 16% of healthcare associated infections, and are associated with considerable morbidity, mortality and increased costs of care. Ensuring evidence-based practice to prevent SSI is incorporated across the patient's surgical journey is complex. OneTogether is a quality improvement collaborative of infection prevention and operating department specialists, formed to support the spread and adoption of best practice to prevent SSI. This paper describes the findings of an expert workshop on infection prevention in operating departments. METHODS: A total of 84 delegates from 75 hospitals attended the workshop, comprising 46 (55%) theatre nurses/operating department practitioners; 16 (19%) infection control practitioners and 22 (26%) other healthcare practitioners. Discussion focused on evidence, policy implementation and barriers to best practice. Responses were synthesised into a narrative review. RESULTS: Delegates reported significant problems in translating evidence-based guidance into everyday practice, lack of local polices and poor compliance. Major barriers were lack of leadership, poorly defined responsibilities, and lack of knowledge/training. CONCLUSIONS: This workshop has provided important insights into major challenges in assuring compliance with best practice in relation to the prevention of SSI. The OneTogether partnership aims to support healthcare practitioners to improve the outcomes of patients undergoing surgery by reducing the risk of SSI. PMID- 28989417 TI - IPS Spotlight. PMID- 28989415 TI - Report of an outbreak of Clostridium difficile infection caused by ribotype 053 in a neurosurgery unit. AB - BACKGROUND: We describe an outbreak of Clostridium difficile infection (CDI) with ribotype 053, a possible hypervirulent strain that causes outbreaks, in a neurosurgical unit. OUTBREAK INVESTIGATION: The outbreak was investigated by creating a timeline of all toxin positive patients with root cause analysis, supplemented with ribotyping results, hand hygiene and environmental audits. There were five cases of CDI, three caused by ribotype 053 indicating transmission. INFECTION PREVENTION MEASURES: These included a short period of ward closure to allow enhanced cleaning, including use of vaporised hydrogen peroxide, isolation of infected patients, reinforcement of hand hygiene, education of all staff on C. difficile, reduction of shared bay occupancy from six to four, and addressing staffing levels. DISCUSSION: The patients with ribotype 053 all had long inpatient stays and had required several courses of broad-spectrum antibiotics for aspiration pneumonia. They also required enteral feeding, which can cause diarrhoea, and during long inpatient stays they had multiple toxin negative faecal samples making clinical diagnosis of CDI difficult. Hence they were not isolated promptly, leading to transmission. This is the first reported outbreak of C. difficile ribotype 053 in the UK and highlights the unique aspects of an outbreak in neurosurgical patients. PMID- 28989418 TI - Diary. PMID- 28989419 TI - Hand hygiene and human factors. PMID- 28989421 TI - A discourse analysis of hand hygiene policy in NHS Trusts. AB - INTRODUCTION: Healthcare-associated infection is a major patient safety concern. Hand hygiene is widely thought to be the single most important measure to affect reductions but compliance is problematic. Producing policies that clearly outline the responsibilities of staff is seen as a key way to instil accountability and improve performance. OBJECTIVES: The purpose of this study is to examine the discourse of hand hygiene policies across 359 NHS Trusts in England and consider the implications for practice. METHOD: The data were examined by combining the techniques of corpus linguistics with critical discourse analysis to generate keywords and concordance lines and then to make an interpretation what this may mean for the healthcare worker. RESULTS: High frequency words such as 'must', 'should', 'will', 'responsible', 'compliance' and 'audit' suggest a tone that is authoritative and unyielding. This creates a fractured relationship between those who produce policies and the healthcare workers who need to comply with them. CONCLUSION: In their intentions to advance patient care policy, producers take little account of the messy, contextual factors that make the recommendations challenging to implement in daily practice. Firstly, Trusts should consider the use language that acknowledges the dynamic nature of practice and, secondly, cease using audit data as an indicator of performance as the conditions under which information is collected lacks reliability. PMID- 28989422 TI - Exploring the approaches used to teach concepts of hand hygiene to Australian medical students. AB - BACKGROUND: Recent audit data has revealed that the hand hygiene (HH) rates of Australian medical students is suboptimal. It has been suggested that new approaches are needed to teach students about infection control. As a first step, we undertook a study to determine the current educational approaches used to teach Australian medical students about HH. Secondly, this study aimed to explore the perceived barriers and to explore what other teaching approaches could be used to improve the levels of knowledge and compliance. METHODS: A self administered questionnaire was sent to the Dean of Medical Education at each of the medical schools in late 2012. RESULTS: Of the 19 medical schools in Australia, 17 agreed to participate. The most commonly reported approaches currently used to teach students about HH are skills stations (17/17) and case scenarios/lectures (15/17). Clinical practical exams (15/17) and competency checks (11/17) are mostly used to assess the HH practices of medical students. Participants nominated the following as barriers to improving HH compliance: negative role modelling by senior doctors, and negative attitudes of students. Practical exercises (15/17), online teaching (12/17) and reflection (12/17) were suggested as other useful approaches that could be used to teach these concepts. CONCLUSION: Practical laboratory-based approaches were suggested as the most useful teaching and learning approach. Given the trend towards blended learning, universities may want to consider new HH teaching approaches that combine campus based learning with online components and reflection. Early exposure and the continued reinforcement of HH concepts through the student's medical degree are essential. PMID- 28989423 TI - 'I don't want to cause any trouble': the attitudes of hospital patients towards patient empowerment strategies to reduce healthcare-acquired infections. AB - BACKGROUND: Patients have, traditionally, been assumed to be the passive party in the healthcare-associated infections equation, with relatively little research focused on the patients' perspective. This study aimed to explore the attitudes of hospital patients towards patient empowerment as one of the key components of patient engagement. METHODS: Semi-structured interviews were undertaken with surgical patients from a major public hospital in Sydney, Australia. FINDINGS: While participants acknowledged that patients could play a role in preventing infections while in hospital, that role was largely associated with maintaining their own personal hygiene. No reference was made to patients interacting with staff members. Some participants said that they would feel comfortable and happy to engage with staff, while others voiced concerns. Some about not wanting to 'cause trouble or start fires' and therefore would not tell staff members to perform hand hygiene. Some participants articulated a fear that their care may be negatively affected if they directly engaged or confronted clinicians about their behaviours. CONCLUSION: We found that patient engagement remains an underused method of preventing healthcare-associated infections, and the deep-seated public fears about individual vulnerabilities still need to be addressed. PMID- 28989424 TI - An outbreak of invasive group A streptococcal infection among elderly patients receiving care from a district nursing team, October 2013 - May 2014. AB - Between October 2013 and April 2014 five elderly patients living within a 2 square mile radius, were admitted to local hospitals with severe group A streptococcal cellulitis and septicaemia. Molecular typing confirmed four patients for whom typing results were available to have the same emm gene sequence type, emm st89. An outbreak investigation was launched and identified that each patient had received care interventions from a district nursing team at their home or local health clinic in the 7 days prior to onset of symptoms. PMID- 28989420 TI - Impact of the International Nosocomial Infection Control Consortium (INICC) Multidimensional Hand Hygiene Approach, over 8 years, in 11 cities of Turkey. AB - AIMS: To evaluate the effectiveness of the International Nosocomial Infection Control Consortium (INICC) Multidimensional Hand Hygiene Approach in Turkey and analyse predictors of poor hand hygiene compliance. DESIGN: An observational, prospective, interventional, before-and-after study was conducted from August 2003 to August 2011 in 12 intensive care units (ICU) of 12 hospitals in 11 cities. The study was divided into a baseline and a follow-up period and included random 30-minute observations for hand hygiene compliance in ICU. The hand hygiene approach included administrative support, supplies availability, education and training, reminders in the workplace, process surveillance, and performance feedback. RESULTS: We observed 21,145 opportunities for hand hygiene. Overall hand hygiene compliance increased from 28.8% to 91% (95% CI 87.6-93.0, p 0.0001). Multivariate and univariate analyses showed that several variables were significantly associated with poor hand hygiene compliance: males vs. females (39% vs. 48%; 95% CI 0.79-0.84, p 0.0001), ancillary staff vs. physicians (35% vs. 46%, 95% CI 0.73-0.78, p 0.0001), and adult vs. pediatric ICUs (42% vs. 74%, 95% CI 0.54-0.60, p 0.0001). CONCLUSIONS: Adherence to hand hygiene was significantly increased with the INICC Hand Hygiene Approach. Specific programmes should be directed to improve hand hygiene in variables found to be predictors of poor hand hygiene compliance. PMID- 28989427 TI - The future is bright? PMID- 28989428 TI - IPS Spotlight. PMID- 28989425 TI - Multiple drug resistant organisms in healthcare: the failure of contact precautions. PMID- 28989430 TI - Different perspectives, same goals. PMID- 28989429 TI - Diary. PMID- 28989431 TI - Evaluation of practice change in Tanzanian health professionals 12 months after participation in an Infection Prevention and Management Course. AB - BACKGROUND: Hospital-acquired infection (HAI) is a problem confronting developing countries. Education programmes have been shown to be effective in increasing awareness and changing practice in health professionals. METHODS: Practice change in health professionals who completed an Infection Prevention and Management Course in Tanzania was explored via focus group 12 months after completion of the course. FINDINGS: Positive changes in infection control practice were found, along with barriers to more widespread change. CONCLUSIONS: Providing tailored and continuing education programs to hospital staff, including managers, is recommended. PMID- 28989432 TI - Using surveillance data to reduce healthcare-associated infection: a qualitative study in Sweden. AB - INTRODUCTION: Healthcare-associated infection (HAI) surveillance data can be used to estimate the scope, spread and location of infections, monitor trends, evaluate preventive efforts, and improve practices, policy and facility planning. In Sweden, national point prevalence surveys (PPS) have been conducted twice yearly in all county councils since 2008. AIM: The aim of this study was to identify key obstacles concerning the HAI surveillance process. METHODS: Twenty two infection control practitioners (ICPs) from all county councils in Sweden were interviewed, using semi-structured interview guides. Data were analysed using qualitative content analysis. RESULTS: Sixteen types of obstacles pertaining to four surveillance stages were identified. Most obstacles were associated with the first two stages, which meant that the latter stages of this process, i.e. the use of the results to reduce HAI, were underdeveloped. The ICPs observed scepticism towards both the PPS methodology itself and the quality of the HAI data collected in the PPS, which hinders HAI surveillance realising its full potential in Swedish healthcare. PMID- 28989433 TI - Outbreak column 17: Situational Awareness for healthcare outbreaks. AB - Outbreak column 17 introduces the utility of Situation Awareness (SA) for outbreak management. For any given time period, an individual or team's SA involves a perception of what is going on, meaning derived from the perception and a prediction of what is likely to happen next. The individual or team's SA informs, but is separate to, both the decisions and actions that follow. The accuracy and completeness of an individual or team's SA will therefore impact on the effectiveness of decisions and actions taken. SA was developed by the aviation industry and is utilised in situations which, like outbreaks, have dynamic, i.e. continuously changing problem spaces, and wherein a loss of SA is likely to lead to both poor decision-making and actions with potentially fatal consequences. The potential benefits of using SA for outbreaks are discussed and include: (1) retrospectively to identify if poor decision-making was a result of a poor SA; (2) prospectively to identify where the system is weakest; and (3) as a teaching tool to improve the skills of individuals and teams in developing a shared understanding of the here and now. PMID- 28989434 TI - Public involvement - benefit or burden? PMID- 28989436 TI - IPS spotlight. PMID- 28989437 TI - Diary. PMID- 28989438 TI - Editorial: the art of scientific publication. PMID- 28989439 TI - A case study of healthcare professional views on the meaning of data produced by hand hygiene auditing. AB - BACKGROUND: Measurement of hand hygiene (HH), crucial for patient safety, has acknowledged flaws stemming from methods available. Even direct observation, the World Health Organization gold standard, may lead to behaviour changes which can affect outcome validity. However, it remains important to understand current levels of HH to allow targeted interventions to be developed. This has resulted in wider adoption of auditing processes. AIM: This study addressed how healthcare professionals perceive data generated by HH auditing processes. METHODS: Qualitative study involving participatory observation and semi-structured interviews with 30 healthcare professionals recruited from a large National Health Service (NHS) two-hospital site in England. FINDINGS: Healthcare professionals perceived two main problems with HH measurement, both associated with feedback: (1) lack of clarity with regard to feedback; and (2) lack of association between training and measurement. In addition, concerns about data accuracy led the majority of participants (22/30) to conclude audit feedback is often 'meaningless'. CONCLUSION: Healthcare professionals require meaningful data on compliance with HH to engender change, as part of a multimodal strategy. Currently healthcare professionals perceive that data lack meaning, and are not seen as drivers to improve HH performance. Potential opportunities to change practice and improve HH are being missed. PMID- 28989440 TI - Central venous catheter dressing durability: an evaluation. AB - BACKGROUND: Skin organisms at the insertion site are frequently implicated in central venous catheter blood stream infections (CVC BSIs) yet few studies have compared the durability of CVC dressings in critically ill patients. AIMS: To undertake an evaluation of the durability and associated costs of different CVC dressings. METHODS: Dressing duration was captured prospectively using a pro forma on four different dressings on five critical care units over a 12-month period. Staff received training on CVC dressing evidence-based practices and a 'how to guide' was implemented. FINDINGS: A total of 1229 CVC dressings were observed from 590 CVCs. One dressing had a median (IQR) duration of 68.5 h (range, 32-105 h) compared to a median duration of 43.5, 46.0 and 40.5 h for the other dressings (P <0.001). The mean time to change a CVC dressing was 13.5 min and the cost of a dressing change was in the range of L1.97-4.97. During the 12 month study period we observed a downward trend in CVC BSIs. DISCUSSION: Despite few dressings remaining adherent for 7 days, the low rates of CVC BSI observed suggests good dressing practices. CONCLUSIONS: One dressing appeared more durable than the others, although it was still below the recommended standard and more expensive. PMID- 28989441 TI - Quantifying patient bacterial exposure risk from reusable phlebotomy tourniquets in a New Zealand secondary level hospital. AB - AIM: This study aimed to assess for the presence of multi-drug resistant organisms (MDROs) on tourniquets and quantify the number of bacteria to which patients might be exposed with each blood collection episode. METHODS: Tourniquets were randomly sampled in a 246-bed, secondary level, New Zealand hospital, which is currently non-endemic for MDROs. A 6-cm length of each tourniquet sampled was applied to the surface of an agar plate and the colony forming units (CFUs) were enumerated. All colonies were then screened for MDROs using standard methods. CFU counts per linear centimetre were multiplied by a range of patient arm circumference measurements. Comparison was also made between non-disinfected tourniquets left on the wards and phlebotomy service tourniquets after daily decontamination with a proprietary disinfectant. RESULTS: The median exposure risk from non-disinfected tourniquets was 173 CFUs per collect (95% CI, 104-861). None of the general ward tourniquets grew any MDROs but four out of five dedicated, single-patient reusable isolation room tourniquets grew MRSA. Disinfected tourniquets had few if any CFUs and CFU counts were significantly lower than non-disinfected tourniquets (P = 0.0001). CONCLUSION: The quantitative risk from reusable tourniquets appears low in the setting of MDRO non-endemicity, with the application of standard infection control practices. PMID- 28989442 TI - Outbreak column 18: The undervalued work of outbreak: prevention, preparedness, detection and management. AB - There are oft-quoted studies which advise that between 1% and 10% of healthcare associated infections (HAIs) present as healthcare-associated outbreaks (HAOs). Examination of these studies showed they lacked validity due to a low sensitivity to detect HAO, and because they pre-date both advanced healthcare systems and the emergence of recent nosocomial pathogen challenges. The accepted inference: that as there are so few HAOs the focus of surveillance programmes should be on endemic and not epidemic infections (outbreaks), is therefore called into question. Current estimates of HAI burden are derived from Point Prevalence Surveys (PPS) which are neither designed to nor are capable of detecting HAOs. We considered the extensive Infection Prevention and Control Team (IPCT) work to prevent and prepare for perennial and novel HAOs and suggest that at present this endeavour is largely unseen, underestimated and undervalued. Any HAI burden estimate needs to comprise a more complete HAI summary than PPS data. This can only be done with a more inclusive surveillance system that has a wider focus than just prevalent infections. There is a real risk of redirection of the IPCT resource from outbreak prevention and preparedness work towards HAI that are counted: such a change could only further increase HAO risks. PMID- 28989445 TI - Diary. PMID- 28989444 TI - IPS spotlight. PMID- 28989446 TI - Norovirus: increasing the index of suspicion. PMID- 28989447 TI - The Where is Norovirus Control Lost (WINCL) Study: an enhanced surveillance project to identify norovirus index cases in care settings in the UK and Ireland. AB - BACKGROUND: Norovirus outbreaks have a significant impact on all care settings; little is known about the index cases from whom these outbreaks initiate. AIM: To identify and categorise norovirus outbreak index cases in care settings. METHODS: A mixed-methods, multi-centre, prospective, enhanced surveillance study identified and categorised index cases in acute and non-acute care settings. RESULTS: From 54 participating centres, 537 outbreaks were reported (November 2013 to April 2014): 383 (71.3%) in acute care facilities (ACF); 115 (21.4%) in residential or care homes (RCH) and 39 (7.3%) in other care settings (OCS). Index cases were identified in 424 (79%) outbreaks. Of the 245 index cases who were asymptomatic on admission and not transferred within/into the care setting, 123 (50%) had been an inpatient/resident for 4 days. Four themes emerged: missing the diagnosis, care service under pressure, delay in outbreak control measures and patient/resident location and proximity. CONCLUSION: The true index case is commonly not identified as the cause of a norovirus outbreak with at least 50% of index cases being misclassified. Unrecognised norovirus cross-transmission occurs frequently suggesting that either Standard Infection Control Precautions (SICPs) are being insufficiently well applied, and or SICPs are themselves are insufficient to prevent outbreaks. PMID- 28989448 TI - The antimicrobial stewardship program in Gulf Cooperation Council (GCC) states: insights from a regional survey. AB - OBJECTIVES: The purpose of the current study is to describe the prevalence and characteristics of antimicrobial stewardship programs (ASP) in Gulf Cooperation Council (GCC) states to explore opportunities and overcome barriers to effective ASP implementation. METHODS: A cross-sectional questionnaire survey was used to evaluate the current status of ASP: major stewardship components, barriers of implementation and program impact in acute care hospitals of GCC states. RESULTS: Forty-seven healthcare professionals responded from four GCC states, the majority from Saudi Arabia (81%). Twenty-nine (62%) participating hospitals had ASP in place. Of these established programs, 35 (75%) reported lack of funding and personnel as major barriers to program implementation. The top three objectives cited for the hospital ASP were to reduce resistance (72.3%), improve clinical outcomes (70.2%) and reduce costs (44.7%). The reported impact of existing ASP was reduction of inappropriate prescribing (68%), reduction of broad spectrum antibiotic use (63.8%), reduction of healthcare-associated infections (61.7%), reduction of length of stay or mortality metrics (59.6%), reduction in direct antibiotic cost (57.4%) and reduction of reported antibiotic resistance (55.3%). CONCLUSION: Survey participants from GCC states who have implemented ASP report significant impacts in the reduction of broad spectrum antibiotic use, hospital acquired infection, inappropriate prescribing and antimicrobial resistance. These findings suggest a promising opportunity to enhance existing ASP through sharing of best practices and support the development of regional guidelines across GCC states. PMID- 28989449 TI - Potential infection control risks associated with roaming healthcare industry representatives. AB - BACKGROUND: Healthcare industry representatives (HCIR) visit multiple hospitals every day. Most enter hygiene sensitive areas and work in close proximity to caregivers and patients. OBJECTIVE: The objective of the present study was to evaluate the HCIRs' current status in hygiene training and vaccination. METHODS: An anonymous walking intercept study was used based on questionnaires to evaluate industry representatives in comparison to physicians and nurses (n = 311 participants, participation rate 30.2%) after their visit to the MEDICA Congress. The valid participants consisted of HCIR (n = 208), hospital nurses (n = 49) and physicians (n = 41). A total of 82.2% (n = 171) HCIR worked in varying hospitals. RESULTS: They frequently request access to hygiene and data-privacy sensitive areas: Among them 51.9% (n = 108) accessed the outpatient clinic, 41.8% (n = 87) the operating room (OR), 33.7% (n = 70) the central supply and sterilisation department (CSSD), and 32.7% (n = 68) the intensive care unit. HCIR requesting access to hygiene sensitive areas showed the lowest scores in hygiene training and a significantly lower Hepatitis B vaccination status, i.e. 37.5% compared to 70.7% for physicians and 53.1% for nurses. DISCUSSION: Status of HCIR hygiene training was inadequate - as was vaccination and contamination control. Therefore, HCIR are exposed to increased infection risk and may unknowingly act as infection vector between different hospitals. PMID- 28989450 TI - Are you serious? From fist bumping to hand hygiene: Considering culture, context and complexity in infection prevention intervention research. AB - Infection prevention is an under-resourced research and development topic, with limited evidence for practice in the most basic of measures. A survey of IPS R&D members indicated that what might appear to be simple interactions and interventions in healthcare, such as hand shaking and hand hygiene, should be considered complex interventions taking account of behaviour at the individual and social level as well as contextual factors. Future studies need to be designed utilising comprehensive approaches, for example, the Medical Research Council complex interventions framework, tailored to the country and more local cultural context, if we are to be serious about evidence for infection prevention and control practice. PMID- 28989452 TI - Reflections from Infection Prevention 2015: beating the bugs, improving the systems and thinking outside the box. PMID- 28989453 TI - Diary. PMID- 28989454 TI - The all-important 'how to': Infection Prevention and Implementation Science. PMID- 28989455 TI - Decontamination of breast pump milk collection kits and related items at home and in hospital: guidance from a Joint Working Group of the Healthcare Infection Society & Infection Prevention Society. AB - INTRODUCTION: A variety of methods are in use for decontaminating breast pump milk collection kits and related items associated with infant feeding. This paper aims to provide best practice guidance for decontamination of this equipment at home and in hospital. It has been compiled by a joint Working Group of the Healthcare Infection Society and the Infection Prevention Society. METHODS: The guidance has been informed by a search of the literature in Medline, the British Nursing Index, the Cumulative Index to Nursing & Allied Health Literature, Midwifery & Infant Care and the results of two surveys of UK neonatal units in 2002/3 and 2006, and of members of the Infection Prevention Society in 2014. Since limited good quality evidence was available from these sources much of the guidance represents good practice based on the consensus view of the Working Group. KEY RECOMMENDATIONS: Breast pump milk collection kits should not be reused by different mothers unless they have been sterilized in a Sterile Services Department between these different users.When used by the same mother, a detergent wash followed by thorough rinsing and drying after each use gives acceptable decontamination for most circumstances, as long as it is performed correctly.Additional decontamination precautions to washing, rinsing and drying may be used if indicated by local risk assessments and on advice from the departmental clinicians and Infection Prevention and Control Teams. The microbiological quality of the rinse water is an important consideration, particularly for infants on neonatal units.If bottle brushes or breast/nipple shields are used, they should be for use by one mother only. Decontamination should be by the processes used for breast pump milk collection kits.Dummies (soothers, pacifiers or comforters) needed for non-nutritive sucking by infants on neonatal units, should be for single infant use. Manufacturers should provide these dummies ready-to-use and individually packaged. They must be discarded at least every 24 hours or immediately if soiled with anything other than the baby's saliva. No attempt should be made to decontaminate the dummies, either before or during use. CONCLUSION: This guidance provides practical recommendations to support the safe decontamination of breast pump milk collection kits for healthcare professionals to use and communicate to other groups such as parents and carers. PMID- 28989456 TI - Development of the UK Vessel Health and Preservation (VHP) framework: a multi organisational collaborative. AB - Vascular access is an important part of many patient care management plans but has some unwanted risks. Previous work published by Moureau et al. (2012) inspired a working group led by the UK Infection Prevention Society (IPS) to produce a vessel health and preservation (VHP) framework. This was with the intention of producing a resource for frontline staff to be able to assess and select the best vascular access device to meet the individual patient's needs and to preserve veins for future use. The working group produced a framework that used available evidence, expert opinion and some small scale testing of the components of the framework. The work so far has received positive feedback but further work is required to formally evaluate the VHP framework in clinical practice to measure both staff knowledge and patient outcomes. PMID- 28989457 TI - Using the Behaviour Change Wheel in infection prevention and control practice. AB - The Centre for Behaviour Change at University College London (UCL) is a new venture that has grown out of the work that we have been doing in the Health Psychology Research Group at UCL and seeks to harness the different pockets of behaviour change work in different disciplines across UCL. A lot of our work in health focuses on the adoption of evidence-based guidelines in practice; not just designing and evaluating interventions, but also developing usable tools for people who are tasked with changing behaviours. These tools aim to enable those who do not necessarily have a background in behavioural science to understand the behaviours they are trying to change and design appropriate interventions. PMID- 28989458 TI - Implementing change: lessons from the patient safety movement. PMID- 28989459 TI - Lessons in implementing infection prevention. AB - This paper has been developed from a conference presentation given by Professor Alison Holmes at the IPS Learning Labs launch event (2015). In it the implementation of research into clinical practice is discussed with reference to the upcoming Health Foundation Spotlight Report. The difficulties of engaging those in clinical practice are discussed with the importance of involvement of clinical leaders being highlighted. The importance of recognising that implementation science as a social process to bring credibility and legitimacy is also stressed. Following this, the Spotlight Report that is focused on strengthening implementation in the UK is discussed. There remains considerable scope for improvement and the impact of surveillance, targets and fatigue are considered. The tension between top-down and bottom-up approaches to implementation are discussed and a recommendation for a blended approach when implementing measures that are the components of an organisational infection prevention and control strategy is proposed. There also needs to be more scrutiny of the reasons for the failure of research implementation through an examination of the 'soft periphery' that comprises the organisational structure, systems and people that will be responsible for implementing and sustaining an intervention. PMID- 28989463 TI - Diary. PMID- 28989461 TI - Spotlight on the IPS Team of the Year 2015. PMID- 28989464 TI - Antimicrobial stewardship: a personal and professional challenge. PMID- 28989466 TI - Incidence and risk factors of infections associated with peripheral intravenous catheters. AB - AIM: To study the incidence and risk factors of bacterial colonisation of peripheral venous catheters during the early neonatal period. DESIGN: Prospective observational clinical study. SETTING: Level II neonatal intensive care unit. PATIENTS: Consecutive neonates in whom peripheral catheter was inserted were recruited. METHODS: The insertion site was cleaned with isopropyl alcohol and chlorhexidine for 30 s consecutively. A needleless catheter access device was attached to peripheral catheters. A dedicated observer reviewed the catheter sites regularly for complications. On removal, the tip of the catheter was cut under sterile conditions and sent to the laboratory for culture. Only catheters indwelling for >12 h were sent for culture. FINDINGS: Bacteria were isolated from 22 out of 154 catheter tips. Methicillin-sensitive Staphylococcus aureus (n = 13) was the most common organism constituting more than 50% of isolates. In five out of 22 isolates, the organism from the catheter tip was identical to the one from the skin. Systemic sepsis at enrolment was positively associated with colonisation of peripheral catheter. None of the neonates developed peripheral catheter-related bloodstream infection. CONCLUSION: When proper infection control measures are in place, risk of peripheral venous catheter-related infection appears extremely low in spite of frequent colonisation of the catheter. PMID- 28989465 TI - A whole health economy approach to reducing MRSA bacteraemia incidence in diabetic foot ulcer patients. AB - INTRODUCTION: Ulceration of the foot is a common problem among diabetic patients. Infection is a major risk in diabetic foot ulcers (DFU) and many of these are caused by Staphylococcus aureus, in particular meticillin-resistant strains (MRSA). The control and management of MRSA remains a significant challenge and all healthcare organisations in England are required to meet Zero Tolerance Objectives for cases of MRSA bacteraemia (MRSAB). This paper describes a collaborative approach across the health economy to investigate factors contributing to the acquisition of MRSA and MRSAB among DFU patients and make improvements to care to reduce the risk of healthcare-associated infections. METHODS: A collaborative approach between acute and community healthcare providers and commissioners was used to conduct Root Cause Analysis and drive improvement to prevent MRSA transmission in DFU patients. RESULTS: Screening of all DFU patients was initiated after 6 MRSAB were found to be associated with in DFU. In total 15 patients with the same MRSA antibiogram were identified. Following the implementation of actions focused on isolation, wound management, screening and cleaning no further cases were identified. CONCLUSION: This outbreak has demonstrated the value of cross-sector collaboration in investigating HCAI in patients with DFU, improving patient care and reducing the risk of MRSA transmission in these vulnerable patents. PMID- 28989467 TI - A cross-sectional survey of the acceptability of data collection processes for validation of a European point prevalence survey of healthcare-associated infections and antimicrobial use. AB - BACKGROUND: Statistical measurements alone are insufficient to ensure robust data for point prevalence surveys (PPS) of healthcare-associated infections (HAI). Data quality is determined by the type of data, data collection methods and available resources. Data collectors' views regarding the acceptability of data collection process for validation studies are also important to consider. AIM: To explore data collectors' views on the acceptability of data collection processes used for a European validation PPS of HAI and antimicrobial use (AMU). METHODS: An anonymous online survey was conducted with 67 data collectors from 10 European countries involved in the study. FINDINGS: Twenty-five (64.1%) participants viewed AMU data collection as easy/quite easy whereas only five (12.8%) thought HAI data collection was easy/quite easy. Six (17%) participants indicated that incentives and 21 (56.8%) that disincentives were possibly/definitely present for reporting cases of HAI. Engagement of staff was not thought to have adversely affected data collection as only one (2.6%) and five (15.4%) participants thought involvement of hospital PPS teams and administration was low/very low, respectively. DISCUSSION: Participants believed the approaches used were appropriate but that more training was required prior to data collection, some case definitions should be reviewed and the number of variables reduced. PMID- 28989468 TI - The reliability of the McCabe score as a marker of co-morbidity in healthcare associated infection point prevalence studies. AB - This study aimed to ascertain the reliability of the McCabe score in a healthcare associated infection point prevalence survey. A 10 European Union Member States survey in 20 hospitals (n = 1912) indicated that there was a moderate level of agreement (kappa = 0.57) with the score. The reliability of the application of the score could be increased by training data collectors, particularly with reference to the ultimately fatal criteria. This is important if the score is to be used to risk adjust data to drive infection prevention and control interventions. PMID- 28989469 TI - Recent emergence of carbapenem-resistant organisms in a low prevalence UK setting in London. AB - Carbapenem-resistant organisms are emerging as a global health threat. The prevalence of CROs in London is largely unknown. A retrospective review of microbiology records indicates an increased in carbapenem-resistant Klebsiella pneumoniae (none in 2011 to 1.3% of 386 in 2013, P = 0.073) and Acinetobacter baumannii (9.1% of 11 in 2011 to 31.2% of 16 in 2013, P = 0.001) in a background of low prevalence at a London hospital. This suggests that CROs may be emerging in our patient population. These increases demand an urgent enhanced surveillance response. PMID- 28989471 TI - IPS Spotlight. PMID- 28989472 TI - Diary. PMID- 28989474 TI - Reporting and case management of occupational exposures to blood-borne pathogens among healthcare workers in three healthcare facilities in Tanzania. AB - BACKGROUND: In sub-Saharan Africa, blood-borne pathogens exposure (BPE) is a serious risk to healthcare workers (HCW). METHODS: We conducted a cross-sectional study assessing BPE among HCW at three public hospitals in Tanzania. From August to November 2012, HCW were surveyed using Audio-Computer Assisted Self-Interview. All HCW at risk for BPE were invited to participate. Factors associated with reporting BPE were identified using logistic regression. FINDINGS: Of the 1102 eligible HCW, 973 (88%) completed the survey. Of these, 690 (71%) were women and 499 (52%) were nurses and nurse assistants. Of the 357 HCW who had a BPE (32%) in the previous 6 months, 120 (34%) reported it. Among these 120 reported exposures, 93 (78%) HCWs reported within 2 h of exposure, 98 (82%) received pre- and post HIV test counselling, and 70 (58%) were offered post-exposure prophylaxis (PEP). Independent factors associated with reporting BPE were being female (adjusted odds ratio [AOR], 2.0; 95% confidence interval [CI], 1.2-3.5), having ever received BPE training (AOR, 2.0; 95% CI, 1.2-3.5), knowledge that HCW receive PEP at another facility (AOR, 2.6; 95% CI, 1.5-4.4), low/no perceived risk related to BPE (AOR, 4.2; 95% CI, 1.9-9.4) and HIV testing within the past year (AOR, 2.3; 95% CI, 1.2-4.4). CONCLUSION: These results highlight the importance of appropriate training on the prevention and reporting of occupational exposure to increase acceptance of HIV testing and improve access to PEP after BPE. PMID- 28989475 TI - Development and appraisal of a hand hygiene teaching approach for medical students: a qualitative study. AB - BACKGROUND: Poor hand hygiene (HH) practices among medical students have previously been attributed to students not being exposed to sufficient teaching materials during their training. AIM: To develop and evaluate a teaching module directed at improving the knowledge and attitudes of undergraduate medical students towards HH. METHODS: The HH teaching module was designed based on educational materials used by the World Health Organization and other patient safety organisations. The development was also informed by the findings from two previous studies including qualitative interviews with staff and students and a survey of Australian medical schools. In-depth group interviews were undertaken with 24 undergraduate medical students. RESULTS: Favourable feedback was received from the interviewed medical students towards the developed scenario-based learning activity; however, the group interview activity was not received well by students. They suggested that the HH teaching activities should be compulsory and not optional for medical students. In order to reinforce good HH practices and to improve knowledge around HH and healthcare-associated infections, they felt that the activities should be repeated during each phase of their degree. CONCLUSIONS: There is a need to change the approach to training in education, particularly to engage students in topics such as HH which are often seen as unimportant. PMID- 28989476 TI - Efficacy of a hospital-wide environmental cleaning protocol on hospital-acquired methicillin-resistant Staphylococcus aureus rates. AB - BACKGROUND: Environmental contamination has been associated with over half of methicillin-resistant Staphylococcus aureus (MRSA) outbreaks in hospitals. We explored if a hospital-wide environmental and patient cleaning protocol would lower hospital acquired MRSA rates and associated costs. OBJECTIVE: This study evaluates the impact of implementing a hospital-wide environmental and patient cleaning protocol on the rate of MRSA infection and the potential cost benefit of the intervention. METHODS: A retrospective, pre-post interventional study design was used. The intervention comprised a combination of enhanced environmental cleaning of high touch surfaces, daily washing of patients with benzalkonium chloride, and targeted isolation of patients with active infection. The rate of MRSA infection per 1000 patient days (PD) was compared with the rate after the intervention (Steiros Algorithm(r)) was implemented. A cost-benefit analysis based on the number of MRSA infections avoided was conducted. RESULTS: The MRSA rates decreased by 96% from 3.04 per 1000 PD to 0.11 per 1000 PD (P <0.0001). This reduction in MRSA infections, avoided an estimated $1,655,143 in healthcare costs. DISCUSSION: Implementation of this hospital-wide protocol appears to be associated with a reduction in the rate of MRSA infection and therefore a reduction in associated healthcare costs. PMID- 28989477 TI - The use of daily electronic prompts to help improve antimicrobial stewardship in a critical care unit. AB - INTRODUCTION: Antimicrobial resistance (AMR) represents a growing threat to public health, with the potential to reverse many of the gains made in modern medicine. AMR is contributed to by both inappropriate choice of antibiotics and inappropriate antibiotic course durations. OBJECTIVES: The objective of this audit was to determine if the introduction of antimicrobial prescribing electronic prompts in an electronic patient record had a positive impact on antimicrobial stewardship. METHODS: The audit examined the proportion of antibiotic prescriptions within a critical care unit in which both a valid stop date and indication were recorded. The audit was repeated on two occasions: first, after an education programme, and second, after the introduction of an electronic prompt within the patients' electronic patient record. RESULTS: Chi square analyses indicated that significant improvements in both the recording of indications (chi2(4) = 39.69, P <0.0001) and stop-dates (chi2(4) = 42.10, P <0.0001) occurred across the three audits. CONCLUSION: We conclude that the novel use of daily electronic prompts has a positive impact on antimicrobial stewardship. PMID- 28989479 TI - IPS Spotlight. PMID- 28989480 TI - Diary. PMID- 28989481 TI - Infection Control Nurses Association' to Infection Prevention Society: 10 years on. PMID- 28989482 TI - Infection risks associated with peripheral vascular catheters. AB - BACKGROUND: Peripheral vascular catheters (PVC) are the most frequently used invasive medical devices in hospitals, with 330 million sold each year in the USA alone. One in three UK inpatients at any one time has at least one PVC in situ according to the Scottish National Prevalence survey. METHOD: A narrative review of studies describing the infection risks associated with PVCs. RESULTS: It is estimated that 30-80% of hospitalised patients receive at least one PVC during their hospital stay. Despite their prevalence, PVCs are not benign devices, and the high number of PVCs inserted annually has resulted in serious catheter related bloodstream infections and significant morbidity, prolonged hospital stay and increased healthcare system costs. To date, PVC infections have been under evaluated. Most studies focus on central venous catheter rather than PVC associated bloodstream infections. Risks associated with PVC infection must be addressed to reduce patient morbidity and associated costs of prolonged hospital admission and treatment. DISCUSSION: This article discusses the sources and routes of PVC-associated infection and outlines known effective prevention and intervention strategies. PMID- 28989483 TI - Characterisation of occupational blood and body fluid exposures beyond the Needlestick Safety and Prevention Act. AB - OBJECTIVE: To describe the use of mandated safety engineered sharps devices (SESDs) and personal protective equipment in healthcare workers (HCWs) with occupational body fluid exposures (BFE) since the Needlestick Safety and Prevention Act. METHODS: Two questionnaires were administered, over 3 years, to HCWs who reported sharps or splash BFEs. Descriptive statistics and chi-square analysis were used. RESULTS: Of the 498 questionnaires completed, nurses completed 262 (53%), house staff 155 (32 %), technicians 63 (13%) and phlebotomists 11 (2%). Four (1%) completers reported 'other' and three (1%) reported unknown. Sharps injuries accounted for 349 (70%) of the BFEs. SESDs were utilised 43% (128/299) of the time with a 54% (70/130) activation rate. Phlebotomists (80%; 8/10) and nurses (59%; 79/267) used SESDs more than doctors (27%; 31/86) and technicians (26%; 10/39) (P <0.0001). Fifty-four percent (185/207) of HCWs reported having had training on SESD use; nurses (64%; 98/154) and phlebotomists (70%; 7/8) significantly more so than house staff (44%; 59/133) and technicians (44%; 21/48) (P <0.05). Most splash BFEs were to the eyes 73% (91/149). Five percent (4/79) of HCWs used protective eyewear. CONCLUSIONS: Systematic regular training, appropriate protocols and iteratively providing the safest SESDs based on HCW experience and technological advances will further reduce the physical and emotional toll of BFEs. PMID- 28989485 TI - Outbreak column 19: needleless connectors (NCs) tales from nine outbreaks. AB - A critical review of historical outbreak reports that are still influencing practice today is presented. These outbreak reports were used as evidence in support of guideline recommendations and of the US Food and Drug Administration's (FDA) advisory notice requiring post-product surveillance for needleless connectors (NC) which have a positive displacement. Guideline recommendations were subsequently changed but not before other authorities had issued recommendations based on the original. All the above led some purchasers to look for different NC designs. The conclusions are that the evidence, as reported, does not support there being an increased risk from positive displacement NCs. Identified in this review were unsubstantiated claims, incompleteness in reporting of specifics, opinions considered as evidence and unexplored outbreak provoking explanations. PMID- 28989484 TI - Needleless connectors: the vascular access catheter's microbial gatekeeper. AB - Needleless connectors (NCs) are essential devices which connect to the end of vascular catheters and enable catheter access for infusion and aspiration. There are various different designs which make it difficult for purchasers to identify the features which present the least risk and greatest safety. The NC is the microbial gatekeeper for vascular catheters; how it is disinfected pre access determines if, and how many, organisms enter and how quickly biofilm will form. This paper will consider these design variations and how differences in antiseptic testing methods have made it difficult to determine the best antiseptic practice pre access. One specific design characteristic is considered: the fluid pathway. The NC's fluid pathway creates a flow which can be either direct to produce a laminar flow or indirect which creates a turbulent flow. At present, the evidence does not support there being an advantage for a specific fluid pathway design in reducing infection risks. PMID- 28989488 TI - Diary. PMID- 28989487 TI - IPS Spotlight. PMID- 28989489 TI - Endorsing Reporting Guidelines: the Journal of Infection Prevention helps show the way! PMID- 28989490 TI - Compliance with infection control standard precautions guidelines: a survey among dental healthcare workers in Hail Region, Saudi Arabia. AB - BACKGROUND: The concept of standard precautions (SP) has been a cornerstone of dental infection control (IC) practice. Full adherence with SP guidelines is still a matter of concern in many institutions. The objectives of the present study were to assess and characterise compliance with SP guidelines among dental healthcare workers (DHCWs) and to analyse factors that affect compliance. METHODS: A regional cross-sectional questionnaire survey among DHCWs in all health facilities was carried out from August to November 2014. RESULTS: A total of 307 returned valid self-report questionnaires with a response rate of 73.1%. Most participants (86.3%) were aware of the SP guidelines, 84.4% received IC training and 88.9% received hepatitis B vaccination. Compliance with SP was found to be high; the majority (90.1%) attained 75% on the compliance scale. In the multivariate logistic regression model, perceived higher institutional commitment as regard IC requirements (odds ratio [OR], 4.34; P <0.001), perceived training as adequate (OR, 3.51; P = 0.003), dentist job (OR, 2.99; P = 0.035) and younger age (OR, 0.59; P = 0.041) were independently predicted as good compliant behaviour. CONCLUSIONS: This survey revealed high self-reported compliance with SP guidelines. Institutional factors appear to have an important role. Attention should be paid to dental assistants and private DHCWs. PMID- 28989491 TI - An evaluation of the effectiveness of an algorithm intervention in reducing inappropriate faecal samples sent for Clostridium difficile testing. AB - BACKGROUND: Clostridium difficile (C. difficile) is a leading cause of infectious diarrhoea in hospitals. Sending faecal samples for testing expedites diagnosis and appropriate treatment. Clinical suspicion of C. difficile based on patient history, signs and symptoms is the basis for sampling. Sending faecal samples from patients with diarrhoea 'just in case' the patient has C. difficile may be an indication of poor clinical management. AIM: To evaluate the effectiveness of an intervention by an Infection Prevention and Control Team (IPCT) in reducing inappropriate faecal samples sent for C. difficile testing. METHOD: An audit of numbers of faecal samples sent before and after a decision-making algorithm was introduced. The number of samples received in the laboratory was retrospectively counted for 12-week periods before and after an algorithm was introduced. FINDINGS: There was a statistically significant reduction in the mean number of faecal samples sent post the algorithm. Results were compared to a similar intervention carried out in 2009 in which the same message was delivered by a memorandum. In 2009 the memorandum had no effect on the overall number of weekly samples being sent. CONCLUSION: An algorithm intervention had an effect on the number of faecal samples being sent for C. difficile testing and thus contributed to the effective use of the laboratory service. PMID- 28989492 TI - Encouraging practitioners in infection prevention and control to publish: a cross sectional survey. AB - AIM: The aim of this cross-sectional survey was to determine the views of infection prevention and control practitioners (IPCPs) on publishing research. METHODS: A convenience sample was obtained by approaching delegates at the 2015 Infection Prevention Society conference and data were captured via a hand-held electronic device. FINDINGS: Of the 79 respondents, most (83%) read the Journal of Infection Prevention (JIP) and found it useful for informing their practice (72%). However, most (91%) had never published in JIP, and less than half (40%) published elsewhere. The main barrier to publication was not having work suitable for publication (38%). Support (37%), training in writing for publication (10%) and time (9%) were considered to be important facilitators in encouraging respondents to publish. DISCUSSION: Strategies that support IPCPs in developing their writing skills may encourage more IPCPs to disseminate evidence to support best practice by publishing their work in peer-reviewed journals. PMID- 28989493 TI - Reduction in methicillin-resistant Staphylococcus aureus colonisation: impact of a screening and decolonisation programme. AB - Patients in care homes are often at 'high risk' of being methicillin-resistant Staphylococcus aureus (MRSA) colonised. Here we report the prevalence of MRSA, the effect of MRSA screening and decolonisation in Wolverhampton care-home residents. Eighty-two care homes (1665 residents) were screened for MRSA, three times at 6-monthly intervals (referred to as phases one, two and three). Screening and decolonisation of MRSA-colonised residents led to a reduction in the prevalence of MRSA from 8.7% in phase one, 6.3% in phase 2 and 4.7% in phase three. Overall, the study suggests that care-home facilities in Wolverhampton are a significant reservoir for MRSA; screening and decolonisation has reduced the risk to residents going for procedures and has indirectly impacted on MRSA rates in the acute Trust. PMID- 28989496 TI - Diary. PMID- 28989495 TI - IPS Spotlight. PMID- 28989497 TI - The Human Immunodeficiency Virus epidemic: where are we now? PMID- 28989498 TI - Two vignettes of adolescent sexual disclosure: guidance for HIV clinical practice. AB - HIV-positive adolescents are required by law to notify sexual partners, but can find it difficult to achieve this goal. This article offers practice guidance for counselling HIV-positive adolescents about sexual disclosure in clinical settings and for building confidence in managing sexual lives with HIV. We use two vignettes to illustrate key differences between perinatally and sexually infected adolescents in terms of readiness to disclose, and include a set of strategies for both groups that can be tailored to individual circumstances and contexts. The toolbox of strategies we describe include pre-counselling, focused counselling, social support groups and technical support. Pre-counselling helps to identify barriers and motivations to sexual disclosure and is followed by counselling sessions in which the focus is on role playing and sexual scripts for disclosure. Peer-led support groups are designed to boost adolescent confidence, and pre-paid cell phones, text messaging, ready-dial phone numbers and a private Facebook page provide back-up support and out-of-hours contact. Since sexual disclosure can be a risky proposition, safety plans, such as having an emergency contact person, should always be in place. These strategies are designed to empower vulnerable adolescents, foster trust between patient and provider, and reduce HIV transmission to sexual partners. PMID- 28989499 TI - Do travel clinic visitors read information on sexual risk abroad in travel health brochures? AB - BACKGROUND: A substantial proportion of travel clinic visitors have sexual encounters while abroad. Hence, guidelines on travel health recommend discussing sexual risk in a pre-travel consultation. However, previous studies showed that it often is not discussed. Although travel clinic visitors usually do receive written information on sexual risk abroad, few data are available on whether this information is read. Therefore, this prospective cohort study in travel clinic visitors was performed. METHODS: Travel clinic visitors were invited to complete a questionnaire after return from their journey. RESULTS: A total of 130 travellers (55%) responded. Half of them recorded they read the information on sexual risk. Male gender (OR 9.94 95% CI 3.12 - 31.63) and 'travelling with others' (OR 2.7 95% CI 1.29 - 5.78) were significant independent predictors of reading the information on sexual risk. High risk travellers, i.e. those travelling without a steady partner, were less likely to have read it. Although websites and apps were mentioned as better methods of providing information, none of the participants visited the websites on sexual behaviour and sexually transmitted infections recommended in the travel health brochure. CONCLUSION: Only half of travel clinic visitors read information on sexual risk in the health brochure received in the clinic and none of them visited the related websites mentioned in the brochure. Further research to identify the most effective way to inform travellers about sexual risk is needed. PMID- 28989501 TI - Understanding disclosure behaviours in HIV-positive young people. AB - Disclosure of sero-status is part of living with HIV and involves a complex decision-making process. Disclosure is not a one-off event and can be viewed as a sequential process and, while affording opportunities for individuals to access appropriate physical and psychological support, it is also an important part of secondary prevention. It is, however, often fraught with emotional challenges, and there is a considerable amount of evidence demonstrating the barriers that individuals face to making a disclosure. Adolescents are one such group that face challenges over disclosing their HIV status. Many adolescents are choosing not to disclose their status, through fear of potentially adverse outcomes, such as rejection and stigma, which could amplify onward transmission rates. In order to better support young people through disclosure journeys, it is essential to understand the reasons and motivations behind why young people choose not to disclose their sero-status in order to develop interventions which may facilitate supporting young people through the disclosure process. PMID- 28989503 TI - Infection Prevention Society Awards 2016. PMID- 28989504 TI - Diary. PMID- 28989505 TI - Credentialing, competence and certification: Infection Prevention and Control as a specialty. PMID- 28989500 TI - Prospective multicentre study in intensive care units in five cities from the Kingdom of Saudi Arabia: Impact of the International Nosocomial Infection Control Consortium (INICC) multidimensional approach on rates of central line-associated bloodstream infection. AB - OBJECTIVE: To analyse the impact of the International Nosocomial Infection Control Consortium (INICC) Multidimensional Approach (IMA) and INICC Surveillance Online System (ISOS) on central line-associated bloodstream infection (CLABSI) rates in five intensive care units (ICUs) from October 2013 to September 2015. DESIGN: Prospective, before-after surveillance study of 3769 patients hospitalised in four adult ICUs and one paediatric ICU in five hospitals in five cities. During baseline, we performed outcome and process surveillance of CLABSI applying CDC/NHSN definitions. During intervention, we implemented IMA and ISOS, which included: (1) a bundle of infection prevention practice interventions; (2) education; (3) outcome surveillance; (4) process surveillance; (5) feedback on CLABSI rates and consequences; and (6) performance feedback of process surveillance. Bivariate and multivariate regression analyses were performed. RESULTS: During baseline, 4468 central line (CL) days and 31 CLABSIs were recorded, accounting for 6.9 CLABSIs per 1000 CL-days. During intervention, 12,027 CL-days and 37 CLABSIs were recorded, accounting for 3.1 CLABSIs per 1000 CL-days. The CLABSI rate was reduced by 56% (incidence-density rate, 0.44; 95% confidence interval, 0.28-0.72; P = 0.001). CONCLUSIONS: Implementing IMA through ISOS was associated with a significant reduction in the CLABSI rate in the ICUs of Saudi Arabia. PMID- 28989507 TI - Reducing the number of missed isolation days in a paediatric high-dependency unit using semi-permanent pods. AB - BACKGROUND: Single rooms are in short supply in many hospitals. AIM: To evaluate the impact of introducing semi-permanent pods to convert multi-occupancy bays into single occupancy pods. METHODS: We performed a 24-month pre-post observational study in a 15-bed paediatric high dependency unit. Three semi permanent pods were installed in February 2013, in the middle of the 24-month period. The percentage of missed isolation days and the proportion of days for which >4 patients required isolation (which would exceed existing isolation facilities) were compared for the year prior to the pods with the first year of pod use using a Fisher's exact tests. RESULTS: Missed isolation days fell from 58.2% (662/1138; 95% confidence interval [CI], 55.3-61.0) pre-pod to 14.8% (205/1382; 95% CI, 13.0-16.8) during the first year of pod use (P <0.001). The percentage of days for which >4 patients required isolation was 74.5% overall (95% CI, 70.5-78.8), and increased from 63% (95% CI, 56.2-69.4) pre-Pod to 86% (95% CI, 80.9-90.3) during pod use (P <0.001). DISCUSSION: The introduction of three semi-permanent pods was feasible in our paediatric HDU setting and reduced the number of missed isolation days, and hence transmission risk, for important hospital pathogens. PMID- 28989506 TI - TWOC around the clock: a multimodal approach to improving catheter care. AB - BACKGROUND: Urinary tract infections (UTI) are the second-largest group of healthcare-associated infections (HCAI). The Saving Lives Urinary Catheter Care Bundle was introduced to reduce catheter-associated urinary tract infections (CAUTI). In response, we implemented a catheter care group to examine ways to improve catheter care in an acute hospital NHS Trust. METHODS: We adopted a multimodal approach, revolving around four components: (1) Catheter Care Pathway; (2) HOUDINI checklist; (3) catheter magnets; and (4) use of bladder ultrasound scanners. RESULTS: The yearly CAUTI prevalence survey showed an annual reduction in CAUTI from 2012-2013 to 2014-2015 (3.5% to 2.4%). Evaluations of the multimodal approach have highlighted limitations, leading to priorities being established around provision of tools, education, and use of measurement and feedback. CONCLUSIONS: Our multimodal approach demonstrates CAUTI rate improvements are achievable, directly benefiting patients. However, long-term maintenance of multimodal components is required to ensure sustained benefit. Engagement and accountability have emerged as significant challenges to the effectiveness and longevity of the catheter care group. We suggest greater emphasis on such challenges if long-term national or international improvement is to be achieved. PMID- 28989508 TI - The utility of electronic health record-based hygiene notes for chlorhexidine bathing practice evaluation. AB - BACKGROUND: Unreliable compliance with infection prevention procedures necessitates an analysis of contributing factors. METHODS: A retrospective study explored utility of 3236 nursing hygiene notes in the electronic healthcare record system (EHR). This 2012-2013 study identified defects in the chlorhexidine (CHG) bathing practice for a hospital unit. RESULTS: The overall compliance with CHG bathing was 22.99%. Patients with length of stay less than 3 days, in most cases, did not have documentation for CHG bathing. Patient refusal to bathe was the most prevalent documented reason (66%) of the unsuccessful initial and repeated offers to bathe. The regular staff were statistically less successful in convincing patients to bathe. The 1455 notes produced by the regular staff (n = 10) demonstrated a significantly higher failure rate (56.08%) to execute this procedure in comparison with 1770 notes documented by the 246 temporary staff (31.19% failure rate) (P value <0.001) . DISCUSSION: This analysis yielded three main insights: lack of the CHG documentation in a large number of short admissions; inconsistent use of CHG baths; and presence of workarounds due to patient refusals to bathe. The study concluded that EHR structured and unstructured data can unlock the opportunity for identifying hidden defects and inform decision-makers about the need for change. PMID- 28989509 TI - Is a chlorine dioxide wiping procedure suitable for the high-level disinfection of nasendoscopes? AB - BACKGROUND: Nasendoscopes are widely used in the outpatient ENT setting. Their reprocessing requires high-level disinfection (HLD). Recently, a wiping procedure using chlorine dioxide (ClO2) has been proposed as an alternative to HLD traditional procedures. OBJECTIVE: To assess the effectiveness of the HLD wiping procedure versus soaking procedure on a contaminated nasendoscope. METHOD: A nasendoscope was contaminated with four strains of bacteria and Bacillus subtilis spores. After HLD either with the wiping procedure or with the soaking procedure (PA), the reduction of the initial contamination was determined. FINDINGS: The wiping procedure with ClO2 displayed more than 5 log reduction for vegetative bacteria after 30 s contact time (CT) and 4 log reduction on B. subtilis spores after 2 min CT. The soaking procedure with PA displayed similar results on planktonic bacteria after 10 min CT but the log reduction of B. subtilis remained below 4. CONCLUSION: The ClO2 wiping procedure showed bactericidal and sporicidal efficacy on a contaminated nasendoscope in a shorter time compared to the PA soaking procedure. Thus, ClO2 wiping procedure might be considered as an alternative to the traditional HLD procedure for nasendoscopes. PMID- 28989512 TI - IPS Spotlight. PMID- 28989510 TI - Managing screening and diagnosis of Zika in the Emergency Department. AB - Zika has emerged as a rapidly spreading infection worldwide. Clinicians in many parts of the world must be prepared to screen for symptoms and diagnose patients with this disease. In particular, pregnant women who may have experienced exposure to Zika must be treated with care and sensitivity due to serious risk for pregnancy complications among those who contract the infection. In response to the outbreak, patient management guidelines have been established for all who may be symptomatic or potentially at risk of infection with Zika. Clinicians globally can prepare to implement such protocols to help contain this disease. PMID- 28989513 TI - Diary. PMID- 28989514 TI - Hand hygiene: From research to action. PMID- 28989515 TI - Hand hygiene among healthcare workers: A qualitative meta summary using the GRADE CERQual process. AB - BACKGROUND: Hand hygiene is considered an effective and potentially modifiable infection control behaviour among healthcare workers (HCW). Several meta-studies have been published that compare quantitatively expressed findings, but limited efforts have been made to synthesise qualitative research. OBJECTIVES: This paper provides the first report of integrated findings from qualitative research reports on hand hygiene compliance among HCW worldwide that employs the GRADE CERQual process of quality assessment. METHODS: We conducted database searches and identified 36 reports in which authors conducted qualitative or mixed methods research on hand hygiene compliance among HCW. We used Dedoose analysis software to facilitate extraction of relevant excerpts. We applied the GRADE-CERQual process to describe relative confidence as high, moderate or low for nine aggregate findings. FINDINGS: Highest confidence findings included that HCW believe they have access to adequate training, and that management and resource support are sometimes lacking. Individual, subjective criteria also influence hand hygiene. DISCUSSION: These results suggest the need for further investigation into healthcare cultures that are perceived as supportive for infection control. Surveillance processes have potential, especially if information is perceived by HCW as timely and relevant. PMID- 28989516 TI - Public perceptions of the use of gloves by healthcare workers and comparison with perceptions of student nurses. AB - INTRODUCTION: There is evidence that non-sterile clinical gloves (NSCG) are over used by healthcare workers (HCWs) and are associated with cross-contamination. This study aimed to determine attitudes of student nurses and members of the public to the use of NSCG. METHODS: Third-year student nurses completed a questionnaire indicating tasks for which they would wear NSCG and influences on their decision. Correlations between tasks were identified using exploratory factor analysis. An online survey of the public was conducted using snowball sampling method. RESULTS: Sixty-seven students completed the questionnaire; they indicated use of NSCG for low-risk tasks and reported their own judgement as the main influence on their decision to wear them. Correlated tasks included 'perceived to be risky' or 'definitive indication for gloves/no gloves' and 'related to personal hygiene'. A total of 142 respondents completed the public survey. They reported being uncomfortable with HCW wearing gloves for some personal tasks, e.g. assisting to toilet and dressing, but 94% preferred their use for washing 'private parts'; 29% had observed inappropriate glove use by HCWs during recent contact with healthcare. CONCLUSION: Student nurses reported using NSCG routinely for tasks for which they are neither required nor recommended. The public observe inappropriate glove use and are uncomfortable with their use for some personal tasks. PMID- 28989517 TI - Healthcare professionals' hand hygiene knowledge and beliefs in the United Arab Emirates. AB - BACKGROUND: Hand hygiene at key moments during patient care is considered an important infection prevention and control measure to reduce healthcare associated infections. While there is extensive research in Western settings, there is little in the United Arab Emirates where particular cultural and religious customs are thought to influence hand hygiene behaviour. AIM: To examine the hand hygiene knowledge and beliefs of health professionals at a tertiary care hospital in the United Arab Emirates. METHODS: A mixed methods design employed a survey followed by focus groups with nurses and doctors. FINDINGS: A total of 109 participants (13.6%) completed the survey: 96 nurses (88%) and 13 doctors (12%). Doctors' hand hygiene knowledge was slightly higher than that of nurses (78.5% versus 73.5%). There was no significant difference in scores on the hand hygiene beliefs scale between nurses (M = 103.06; SD = 8.0) and doctors (M = 99.00; SD = 10.53; t (80) = 1.55; p = 0.13, two-tailed). Seven categories emerged following transcript analysis. DISCUSSION: Hand hygiene knowledge scores suggest further hand hygiene education is required, especially on alcohol-based hand rub use. Addressing doctors' beliefs is particularly important given the leadership roles that doctors play in healthcare settings. PMID- 28989518 TI - The effect of merging two infectious disease units on hand hygiene adherence in Italy. AB - BACKGROUND: Healthcare-associated infections (HAIs) are common and harmful to patients. Effective hand hygiene can help prevent HAIs, however, suboptimal healthcare worker hand hygiene remains problematic across the globe. This study analyses the impact of organisational changes on hand hygiene. METHODS: This observational study assessed hand hygiene by different professions before and after a merger of a recently combined infectious diseases (ID) unit coupled with a qualitative study about barriers to optimal hand hygiene. Direct observations were compared with previous data collected on both units before they merged. We also conducted focus groups with the doctors and nurses about hand hygiene. RESULTS: After two ID units merged in 2013, we observed 681 provider-patient interactions. We compared these with a previous observation period in 2012. Hand hygiene adherence among nurses significantly declined after the merger (from 36% to 24%, P <0.001). However, adherence among doctors increased from 51% to 63% after the merger (P = 0.004). Data from the focus groups revealed a gap between doctor and nurses perceptions of education and goal adherence rates. CONCLUSIONS: Our findings underscore the important role played by effective unit leaders to prevent infection. We found long-term sustainability of hand hygiene practices among doctors. However, adherence among nurses was substantially lower. PMID- 28989521 TI - Diary. PMID- 28989519 TI - Outbreak of vancomycin-resistant enterococcus on a haematology ward: management and control. AB - Vancomycin-resistant enterococci (VRE) infections and outbreaks are still infrequent in Spain. A six-month outbreak, which took place in a haematology ward, its control and management are described in this study. A total of 22 patients were colonised and two bloodstream infections occurred during this period. Even though there were two waves of new colonised patients, a multidisciplinary approach, quick interventions and enhanced infection control policies were required in order to control this outbreak. PMID- 28989523 TI - Preventing surgical site infection: The challenge of 'getting it right first time'. PMID- 28989524 TI - Development of a single, practical measure of surgical site infection (SSI) for patient report or observer completion. AB - BACKGROUND: Surgical site infections (SSIs) are the third most common hospital associated infection and can lead to significant patient morbidity and healthcare costs. Identification of SSIs is key to surveillance and research but reliable assessment is challenging, particularly after hospital discharge when most SSIs present. Existing SSI measurement tools have limitations and their suitability for post-discharge surveillance is uncertain. AIMS: This study aimed to develop a single measure to identify SSI after hospital discharge, suitable for patient or observer completion. METHODS: A three-phase mixed methods study was undertaken: Phase 1, an analysis of existing tools and semi-structured interviews with patients and professionals to establish the content of the measure; Phase 2, development of questionnaire items suitable for patients and professionals; Phase 3, pre-testing the single measure to assess acceptability and understanding to both stakeholder groups. Interviews and pre-testing took place over 12 months in 2014-2015 with patients and professionals from five specialties recruited from two UK hospital Trusts. FINDINGS: Analyses of existing tools and interviews identified 19 important domains for assessing SSIs. Domains were developed into provisional questionnaire items. Pre-testing and iterative revision resulted in a final version with 16 items that were understood and easily completed by patients and observers (healthcare professionals). CONCLUSION: A single patient and observer measure for post-discharge SSI assessment has been developed. Further testing of the validity, reliability and accuracy of the measure is underway. PMID- 28989525 TI - Factors influencing compliance to the infection control precautions among nurses and physicians in Jordan: A cross-sectional study. AB - BACKGROUND: Adherence to infection control precautions (ICP) is important to reduce the transmission of healthcare-associated infections (HAIs). AIMS: To determine nurses and physician's knowledge, attitude and compliance to ICPs and factors associated with reported compliance. METHODS: A cross-sectional survey of nurses and physicians recruited from three hospitals at three different healthcare sectors in Jordan. Three instruments were used to assess knowledge, attitudes and compliance to ICPs. FINDINGS: A total of 211 professionals completed the survey: 155 nurses and 56 physicians. Both groups had low knowledge scores for ICP but a high positive attitude. Although both groups had high reported compliance scores, nurses scores were higher (P = 0.04). Participants from the private hospital had higher knowledge and compliance scores. Length of experience, knowledge and attitude were significant predictors of reported compliance to ICPs. DISCUSSION: Despite poor knowledge, Jordanian healthcare professionals reported high scores for positive attitudes and compliance with IPCs. Clinical training programmes are required to enhance knowledge and understanding of IPCs. PMID- 28989526 TI - Scabies outbreak among healthcare workers in a German acute care hospital. AB - BACKGROUND: This article reports on a scabies outbreak among healthcare workers (HCW) in an acute care hospital. The outbreak was associated with a patient suffering from a chronic skin disease that was later diagnosed as crusted scabies. OBJECTIVE: The objective was to determine the outbreak drivers and define a prevention strategy against future outbreaks. METHODS: All staff that had contact with the patient were treated with 5% permethrin ointment. An interdisciplinary outbreak investigation team was established. The team conducted a questionnaire-based case-control study. FINDINGS: After the permethrin treatment, no further case was found. Twenty-seven HCWs who had contact with the index patient answered the questionnaire (response rate 73%). The outbreak questionnaire revealed 13 cases of secondary scabies among HCWs. In the multivariable analysis, a lack of glove use (odds ratio [OR], 9.8; P value = 0.036) and frequent close physical contact (OR, 8.151; P value = 0.038) were associated with increased risk of scabies acquisition. DISCUSSION: The scabies outbreak was most likely driven by three factors: an index patient with crusted scabies; a delayed diagnosis of this patient; and close physical contact without gloves during his hospital stay. The use of disposable gloves for patients with unclear dermatological diagnosis have the potential to limit future scabies outbreaks. PMID- 28989527 TI - Influenza outbreak in a Canadian correctional facility. AB - Correctional facilities face increased risk of communicable disease transmission and outbreaks. We describe the progression of an influenza outbreak in a Canadian remand facility and suggest strategies for preventing, identifying and responding to outbreaks in this setting. In total, six inmates had laboratory-confirmed influenza resulting in 144 exposed contacts. Control measures included enhanced isolation precautions, restricting admissions to affected living units, targeted vaccination and antiviral prophylaxis. This report highlights the importance of setting specific outbreak guidelines in addressing population and environmental challenges, as well as implementation of effective infection prevention and control (IPAC) and public health measures when managing influenza and other communicable disease outbreaks. PMID- 28989528 TI - Outbreak Column 20: are outbreaks man-made disasters that display intertwined errors of human judgement and behaviour? AB - Man-made disasters are reported to have five intertwined errors of human judgement and behaviour. As outbreaks are essentially man-made disasters, the cited intertwined errors of engineering overreach, smooth sailing fallacy, insider view, risk-seeking incentives and social-herding were looked for in five notable outbreaks of Clostridium difficile infection. Engineering overreach was found to be the most identifiable error. The purpose of this reflective exercise was to turn hindsight into foresight and determine the intertwined levels of safety behaviour needed to prevent any future pathogen emerging to produce healthcare disasters. PMID- 28989530 TI - The national agenda for Healthcare Associated Infection, Antimicrobial Resistance and Infection Prevention and Control in Scotland: Structures, current priorities and programmes. PMID- 28989531 TI - Diary. PMID- 28989532 TI - Disulfide Bond Characterization of Endogenous IgG3 Monoclonal Antibodies Using LC MS: An Investigation of IgG3 Disulfide-mediated Isoforms. AB - The use of monoclonal antibodies (mAbs) for the manufacture of innovator and biosimilar biotherapeutics has increased tremendously in recent years. From a structural perspective, mAbs have high disulfide bond content, and the correct disulfide connectivity is required for proper folding and to maintain their biological activity. Therefore, disulfide linkage mapping is an important component of mAB characterization for ensuring drug safety and efficacy. The native disulfide linkage patterns of all four subclasses of IgG antibodies have been well established since the late 1960s. Among these IgG subtypes, disulfide mediated isoforms have been identified for IgG2 and IgG4, and to a lesser extent in IgG1, which is the most studied IgG subclass. However, no studies have been carried out so far to investigate whether different IgG3 isoforms exist due to alternative disulfide connectivity. In an effort to investigate the presence of disulfide-mediated isoforms in IgG3, we employed a bottom-up mass spectrometry approach to accurately determine the disulfide bond linkages in endogenous human IgG3 monoclonal antibody and our results show that no such alternative disulfide bonds exist. While many antibody-based drugs are developed around IgG1, IgG3 represents a new, and in some cases, more desirable drug candidate. Our data represent the first demonstration that alternative disulfide bond arrangements are not present in endogenous IgG3; and therefore, they should not be present in recombinant forms used as antibody-based therapeutics. PMID- 28989533 TI - Trityl-based alkoxyamines as NMP controllers and spin-labels. AB - Recently, new applications of trityl-nitroxide biradicals were proposed. In the present study, attachment of a trityl radical to alkoxyamines was performed for the first time. The rate constants kd of C-ON bond homolysis in these alkoxyamines were measured and found to be equal to those for alkoxyamines without trityl. The electron paramagnetic resonance (EPR) spectra of the products of alkoxyamine homolysis (trityl-TEMPO and trityl-SG1 biradicals) were recorded, and the corresponding exchange interactions were estimated. The decomposition of trityl-alkoxyamine showed more than an 80% yield of biradicals, meaning that the C-ON bond homolysis is the main reaction. The suitability of these labelled initiators/controllers for polymerisation was exemplified by means of successful nitroxide-mediated polymerisation (NMP) of styrene. Thus, this is the first report of a spin-labelled alkoxyamine suitable for NMP. PMID- 28989534 TI - Activation of Janus kinase 1 confers poor prognosis in patients with non-small cell lung cancer. AB - The activation of Janus kinase 1 (JAK1) has been reported to occur in non-small cell lung cancer (NSCLC), activating the JAK/signal transducers and activators of transcription cascade. However, the association between JAK1 activation and the prognostic value in NSCLC remains unclear. The present study initially investigated the association between expression of the activated form of JAK1 (p JAK1) and prognosis in patients with NSCLC. A cohort of 142 resected primary NSCLC tissue samples, including 74 adenocarcinoma (ADCC) and 68 squamous cell carcinoma samples, were analyzed. p-JAK1 expression status was determined by immunohistochemistry. Evaluation of epidermal growth factor receptor (EGFR) gene amplification by fluorescence in situ hybridization was subsequently performed in 74 ADCC samples. The prognostic significance of p-JAK1 expression and EGFR gene amplification were evaluated with univariate and multivariate survival analyses. Compared with normal lung tissue, p-JAK1 expression level was significantly increased in NSCLC (P<0.001). Positive p-JAK1 expression indicated a poor prognosis, particularly for patients in early stages (stage I/II, including tumor size <3 cm, Lymph node invasion N0/1; all P<0.05). p-JAK1 expression was an independent predictor of a poor prognosis (P=0.022). The overall survival time for patients with positive p-JAK1 expression and EGFR-amplified tumors was significantly shortened compared with patients with tumors negative for one or both features (both features present vs. neither feature present, P<0.001). The results provided clinical evidence that the activation of JAK1 was an independent prognostic factor, particularly in early stage NSCLC. The combination of EGFR gene amplification and p-JAK1 expression may be a novel target for the selection of individual therapy strategies and predicting the effects of therapy for NSCLC. PMID- 28989535 TI - Investigating the microRNA-mRNA regulatory network in acute myeloid leukemia. AB - Acute myeloid leukemia (AML) is a common myelogenous malignancy in adults that is often characterized by disease relapse. The pathophysiological mechanism of AML has not yet been elucidated. The present study aimed to identify the crucial microRNAs (miRNAs/miRs) and target genes in AML, and to uncover the potential oncogenic mechanism of AML. miRNA and mRNA expression-profiling microarray datasets were downloaded from the Gene Expression Omnibus database. Differential expression analysis was performed and a regulatory network between miRNAs and target genes was constructed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were used to predict the biological functions of the differentially expressed genes. Reverse transcription-quantitative polymerase chain reaction analysis was employed to verify the expression levels of miRNAs and target genes in AML patient samples. A total of 86 differentially expressed miRNAs and 468 differentially expressed mRNAs between AML and healthy blood samples were identified. In total, 47 miRNAs and 401 mRNAs were found to be upregulated, and 39 miRNAs and 67 mRNAs were found to be downregulated in AML. A total of 223 miRNA-target genes pairs were subjected to the construction of a regulatory network. Differentially expressed target genes were significantly enriched in the Wnt signaling pathway (hsa04310), melanogenesis (hsa04916) and pathways in cancer (hsa05200). Significantly differentially expressed miRNAs and genes, including hsa-miR-155, hsa-miR-192, annexin A2 (ANXA2), frizzled class receptor 3 (FZD3), and pleomorphic adenoma gene 1 (PLAG1), may serve essential roles in AML oncogenesis. Overall, hsa-miR-155, hsa-miR-192, ANXA2, FZD3 and PLAG1 may be associated with the development of AML via the involvement of the Wnt signaling pathway, melanogenesis and other cancer-associated signaling pathways. PMID- 28989536 TI - Mechanisms of inhibiting human leukemia cell lines by serum of rats treated with compound banmao capsule. AB - Compound banmao capsule (CBC) is a traditional Chinese medicinal formula composed of extracts from 11 organisms. The present study investigated the mechanism of CBC on the biological behavior of human leukemia cell lines using seropharmacological methods. CBC-containing rat serum was prepared by intragastrical administration of CBC to rats. The proliferation of human leukemia HL60 and K562 cell lines was assayed by measuring cell viability with the 3-(4,5 dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium method, while cell cycle distribution and the rate of apoptosis were evaluated with flow cytometry. The mRNA expression of vascular endothelial growth factor A (VEGF-A) and chemotactic and inflammatory genes in human leukemia cell lines was examined using reverse transcription quantitative-polymerase chain reaction methods. It was revealed that the proliferation of K562 and HL60 cells was significantly inhibited by the CBC-containing rat serum at 72 h. The CBC containing serum also promoted the apoptosis of K562 and HL60 cell lines. The CBC containing serum altered the cell cycle progression of K562 and HL60, increasing the proportion of the cells in G1 phase and decreasing the proportion of the cells in S phase. Attenuated expression of VEGF-A and a decreasing trend in the expression of chemotactic and inflammatory genes were identified following treatment with CBC-containing serum in HL60 and K562 cells. In conclusion, CBC containing serum exerted an inhibitory effect on the growth of K562 and HL60 cells by decreasing cellular proliferation, promoting apoptosis and cell cycle arrest, and decreasing the expression of VEGF-A, and chemotactic and inflammatory genes. PMID- 28989537 TI - Effect of inhibiting Beclin-1 expression on autophagy, proliferation and apoptosis in colorectal cancer. AB - The present study aimed to investigate the molecular mechanisms and effect of Beclin-1 on autophagy, proliferation and apoptosis in the colorectal cancer (CRC) HCT116 and SW620 cells. Beclin-1 was silenced by RNA interference (RNAi) in HTC116 and SW620 cells. Reverse transcription-polymerase chain reaction and western blot were used to measure the expression of Beclin-1. The percentage of apoptotic cells was analyzed by cell counting kit-8 (CCK-8) and flow cytometry (FCM). Cell cycle and cell proliferation were analyzed by FCM and the MTT assay. The present study created 3 groups in the two cell lines, consisting of the targeting siRNA (TS) group, in which Beclin-1 was partially silenced, non specific siRNA (NS) group and control group (CG; without transfection). By siRNA transfection, the mRNA and protein level of Beclin-1 in the TS group were significantly inhibited compared with the NS group and CG (P<0.05). After 0, 24, 48 and 72 h, the survival rate of the cells in the TS group was significantly decreased compared with the survival rate of the cells in the NS group and CG, as detected by CCK-8 methods (P<0.05). FCM and MTT results showed the apoptotic rate of the cells in the TS group was significantly decreased compared with the rate in the NS group and CG (P<0.05), and the proliferation of the cells in the NS group was evidently increased compared with the CG. In conclusion, Beclin-1 played an important role in regulating autophagy, proliferation and apoptosis in HCT116 and SW620 cells. The inhibition of Beclin-1 by RNAi suppressed the autophagic activity and proliferation, but promoted apoptosis in CRC cells. Beclin-1 was the new target of gene therapy for CRC. PMID- 28989538 TI - Erratum: Efficacy and tolerability of lacosamide for secondary epileptic seizures in patients with brain tumor: A multicenter, observational retrospective study. AB - [This corrects the article DOI: 10.3892/ol.2017.5988.]. PMID- 28989539 TI - Correction of aberrations in the human eye using computational methods. AB - Phase-sensitive imaging and computational correction of patient-specific optical aberrations enable high-resolution imaging of the human retina to aid diagnosis and treatment of eye diseases. PMID- 28989540 TI - Immunotheranostic Polymersomes Modularly Assembled from Tetrablock and Diblock Copolymers with Oxidation-Responsive Fluorescence. AB - INTRODUCTION: Intracellular delivery is a key step for many applications in medicine and for investigations into cellular function. This is particularly true for immunotherapy, which often requires controlled delivery of antigen and adjuvants to the cytoplasm of immune cells. Due to the complex responses generated by the stimulation of diverse immune cell populations, it is critical to monitor which cells are targeted during treatment. To address this issue, we have engineered an immunotheranostic polymersome delivery system that fluorescently marks immune cells following intracellular delivery. METHODS: N-(3 bromopropyl)phthalimide end-capped poly(ethylene glycol)-bl-poly(propylene sulfide) (PEG-PPS-PI) was synthesized by anionic ring opening polymerization and linked with PEG-PPS-NH2 via a perylene bisimide (PBI) bridge to form a tetrablock copolymer (PEG-PPS-PBI-PPS-PEG). Block copolymers were assembled into polymersomes by thin film hydration in phosphate buffered saline and characterized by dynamic light scattering, cryogenic electron microscopy and fluorescence spectroscopy. Polymersomes were injected subcutaneously into the backs of mice, and draining lymph nodes were extracted for flow cytometric analysis of cellular uptake and disassembly. RESULTS: Modular self-assembly of tetrablock / diblock copolymers in aqueous solutions induced pi-pi stacking of the PBI linker that both red-shifted and quenched the PBI fluorescence. Reactive oxygen species within the endosomes of phagocytic immune cell populations oxidized the PPS blocks, which disassembled the polymersomes for dequenching and shifting of the PBI fluorescence from 640 nm to 550 nm emission. Lymph node resident macrophages and dendritic cells were found to increase in 550 nm emission over the course of 3 days by flow cytometry. CONCLUSIONS: Immunotheranostic polymersomes present a versatile platform to probe the contributions of specific cell populations during the elicitation of controlled immune responses. Flanking PBI with two oxidation-sensitive hydrophobic PPS blocks enhanced pi stacking and introduced a mechanism for disrupting pi-pi interactions to shift PBI fluorescence in response to oxidative conditions. Shifts from red (640 nm) to green (550 nm) fluorescence occurred in the presence of physiologically relevant concentrations of reactive oxygen species and could be observed within phagocytic cells both in vitro and in vivo. PMID- 28989541 TI - A Parallel-Plate Flow Chamber for Mechanical Characterization of Endothelial Cells Exposed to Laminar Shear Stress. AB - Shear stresses induced by laminar fluid flow are essential to properly recapitulate the physiological microenvironment experienced by endothelial cells (ECs). ECs respond to these stresses via mechanotransduction by modulating their phenotype and biomechanical characteristics, which can be characterized by Atomic Force Microscopy (AFM). Parallel Plate Flow Chambers (PPFCs) apply unidirectional laminar fluid flow to EC monolayers in vitro. Since ECs in sealed PPFCs are inaccessible to AFM probes, cone-and-plate viscometers (CPs) are commonly used to apply shear stress. This paper presents a comparison of the efficacies of both methods. Computational Fluid Dynamic simulation and validation testing using EC responses as a metric have indicated limitations in the use of CPs to apply laminar shear stress. Monolayers subjected to laminar fluid flow in a PPFC respond by increasing cortical stiffness, elongating, and aligning filamentous actin in the direction of fluid flow to a greater extent than CP devices. Limitations using CP devices to provide laminar flow across an EC monolayer suggest they are better suited when studying EC response for disturbed flow conditions. PPFC platforms allow for exposure of ECs to laminar fluid flow conditions, recapitulating cellular biomechanical behaviors, whereas CP platforms allow for mechanical characterization of ECs under secondary flow. PMID- 28989542 TI - Cross-over comparison and new chemotherapy regimens in metastatic pancreatic cancer. AB - Despite decades of research, pancreatic ductal adenocarcinoma (PDAC) is still one of the most lethal malignant diseases with a devastating 5-year overall survival of only 4-5%. Indeed, long-term survival was not affected by the introduction of new systemic cytotoxic chemotherapies which remain the key cornerstone in the treatment of metastatic PDAC. In the first-line setting, FOLFIRINOX based upon the results of the PRODIGE/ACCORD trial and gemcitabine with albumin-bound paclitaxel (GNP) based upon the MPACT trial have both been approved as therapeutic options for patients with no significant comorbidities and good performance status. As there is no direct comparison between these regimens, the choice in first-line treatment depends on the toxicity profile, patient's preferences and reimbursability. In the second-line setting, the results of the NAPOLI-1 trial have led to the approval of nanoliposomal irinotecan (nal-iri) in combination with 5-fluorouracil (5-FU) for the treatment of patients with mPDAC progressing under gemcitabine-based chemotherapy and therefore this regimen is the first to be approved for use in second-line therapy. PMID- 28989543 TI - New diagnostic tools for breast cancer. AB - Imaging plays a major role in the diagnosis, treatment, and follow-up of breast cancer. Findings that require further assessment will be detected both at screening and curative mammography. Most findings that are further worked up tend to yield benign diagnoses. Consequently, there is an ongoing search for new tools to reduce recalls and unnecessary biopsies while maintaining or improving cancer detection rates. The clinically most promising methods in this respect are described and discussed in this review. PMID- 28989544 TI - Local therapies for breast cancer. AB - During the San Antonio Breast Cancer Symposium in December 2016, the main topics were systemic treatment of breast cancer and molecular research. But several studies were also presented concerning local therapy: Surgical issues on evaluating resection margins, management of ductal carcinoma in situ (DCIS), surgical challenges after neoadjuvant therapy related to assessment of response or treatment of axillary lymph nodes, and studies about outcome after breast reconstruction and radiation therapy were discussed. In this short review, oral presentations of these topics are summarized. PMID- 28989545 TI - A modified risk set approach to biomarker evaluation studies. AB - There is tremendous scientific and medical interest in the use of biomarkers to better facilitate medical decision making. In this article, we present a simple framework for assessing the predictive ability of a biomarker. The methodology requires use of techniques from a subfield of survival analysis termed semicompeting risks; results are presented to make the article self-contained. As we show in the article, one natural interpretation of semicompeting risks model is in terms of modifying the classical risk set approach to survival analysis that is more germane to medical decision making. A crucial parameter for evaluating biomarkers is the predictive hazard ratio, which is different from the usual hazard ratio from Cox regression models for right-censored data. This quantity will be defined; its estimation, inference and adjustment for covariates will be discussed. Aspects of causal inference related to these procedures will also be described. The methodology is illustrated with an evaluation of serum albumin in terms of predicting death in patients with primary biliary cirrhosis. PMID- 28989546 TI - Too Early to Tell: The Potential Impact and Challenges-Ethical and Otherwise Inherent in the Mainstreaming of Dharma in an Increasingly Dystopian World. PMID- 28989547 TI - Teaching Mindfulness to Teachers: a Systematic Review and Narrative Synthesis. AB - School teachers report high levels of stress which impact on their engagement with pupils and effectiveness as a teacher. Early intervention or prevention approaches may support teachers to develop positive coping and reduce the experience and impact of stress. This article reviews research on one such approach: mindfulness-based interventions (MBIs) for school teachers. A systematic review and narrative synthesis were conducted for quantitative and qualitative studies that report the effects of MBIs for teachers of children aged 5-18 years on symptoms of stress and emotion regulation and self-efficacy. Twelve independent publications were identified meeting the inclusion criteria and these gave a total of 13 samples. Quality appraisal of the identified articles was carried out. The effect sizes and proportion of significant findings are reported for relevant outcomes. The quality of the literature varied, with main strengths in reporting study details, and weaknesses including sample size considerations. A range of MBIs were employed across the literature, ranging in contact hours and aims. MBIs showed strongest promise for intermediary effects on teacher emotion regulation. The results of the review are discussed in the context of a model of teacher stress. Teacher social and emotional competence has implications for pupil wellbeing through teacher-pupil relationships and effective management of the classroom. The implications for practice and research are considered. PMID- 28989549 TI - The Effectiveness of Mindfulness-Based Stress Reduction on Psychological Distress and Cognitive Functioning in Patients with Multiple Sclerosis: a Pilot Study. AB - Patients with multiple sclerosis (MS) often suffer from psychological distress and cognitive dysfunctioning. These factors negatively impact the health-related quality of life. Only recently behavioral therapeutic approaches are being used to treat psychological distress in MS. The aim of the present pilot study was not only to investigate the effectiveness of mindfulness-based stress reduction (MBSR) on psychological distress but also to explore whether it can improve cognitive functioning among patients with MS. Outpatients of the MS Center of the Radboud University Medical Center (Radboudumc) were invited to participate in an MBSR training. Psychological and cognitive measures were administered pre- and post-intervention. Twenty-five MS patients completed the MBSR training and psychological measures, of which 16 patients completed the cognitive tests. Significant improvements were found in depressive symptoms, quality of life, fatigue, mindfulness skills, and self-compassion. Of the cognitive tests, performance on a visual spatial processing test significantly improved after the intervention. Overall, this pilot study showed promising results of the effects of MBSR on reducing psychological distress, and it suggests MBSR might improve cognitive functioning in MS patients. Future randomized controlled trials should be conducted to confirm the possible effectiveness of MBSR-and its long-term effects-on psychological and cognitive functioning in MS patients. PMID- 28989550 TI - Emotion Regulation Mediates the Associations of Mindfulness on Symptoms of Depression and Anxiety in the General Population. AB - In the last decade, clinical research on mindfulness and its positive effects on depression and anxiety have gained increased interest. Emotion regulation mediates the effects of mindfulness on mental health in clinical samples and among meditators. The present study examined whether these associations also generalize to the general population. Multi-group structural equation models tested with a sample of 853 adults whether difficulties in emotion regulation mediated the associations between overall mindfulness in addition to the Observe facet with symptoms of depression and anxiety and whether associations were similar among men and women. Emotion regulation partially mediated the associations of overall mindfulness with symptoms of depression and anxiety; associations with Observe were fully mediated. The magnitude of associations was similar among men and women. Mindfulness exerts positive effects on mental health among the general population mostly via improving emotion regulation. The training of mindfulness and emotion regulation may thus benefit mental health not only in clinical populations but also in the general population. Venues for further research are discussed. PMID- 28989548 TI - Mindful with Your Baby: Feasibility, Acceptability, and Effects of a Mindful Parenting Group Training for Mothers and Their Babies in a Mental Health Context. AB - Many mothers experience difficulties after the birth of a baby. Mindful parenting may have benefits for mothers and babies, because it can help mothers regulate stress, and be more attentive towards themselves and their babies, which may have positive effects on their responsivity. This study examined the effectiveness of Mindful with your baby, an 8-week mindful parenting group training for mothers with their babies. The presence of the babies provides on-the-spot practicing opportunities and facilitates generalization of what is learned. Forty-four mothers with their babies (0-18 months), who were referred to a mental health clinic because of elevated stress or mental health problems of the mother, infant (regulation) problems, or mother-infant interaction problems, participated in 10 groups, each comprising of three to six mother-baby dyads. Questionnaires were administered at pretest, posttest, 8-week follow-up, and 1-year follow-up. Dropout rate was 7%. At posttest, 8-week follow-up, and 1-year follow-up, a significant improvement was seen in mindfulness, self-compassion, mindful parenting, (medium to large effects), as well as in well-being, psychopathology, parental confidence, responsivity, and hostility (small to large effects). Parental stress and parental affection only improved at the first and second follow-ups, respectively (small to medium effects), and maternal attention and rejection did not change. The infants improved in their positive affectivity (medium effect) but not in other aspects of their temperament. Mindful with your baby is a promising intervention for mothers with babies who are referred to mental health care because of elevated stress or mental health problems, infant (regulation) problems, or mother-infant interaction problems. PMID- 28989551 TI - Mindfulness Mechanisms in Sports: Mediating Effects of Rumination and Emotion Regulation on Sport-Specific Coping. AB - The main objective of the project was to examine a proposed theoretical model of mindfulness mechanisms in sports. We conducted two studies (the first study using a cross-sectional design and the second a longitudinal design) to investigate if rumination and emotion regulation mediate the relation between dispositional mindfulness and sport-specific coping. Two hundred and forty-two young elite athletes, drawn from various sports, were recruited for the cross-sectional study. For the longitudinal study, 65 elite athletes were recruited. All analyses were performed using Bayesian statistics. The path analyses showed credible indirect effects of dispositional mindfulness on coping via rumination and emotion regulation in both the cross-sectional study and the longitudinal study. Additionally, the results in both studies showed credible direct effects of dispositional mindfulness on rumination and emotion regulation. Further, credible direct effects of emotion regulation as well as rumination on coping were also found in both studies. Our findings support the theoretical model, indicating that rumination and emotion regulation function as essential mechanisms in the relation between dispositional mindfulness and sport-specific coping skills. Increased dispositional mindfulness in competitive athletes (i.e. by practicing mindfulness) may lead to reductions in rumination, as well as an improved capacity to regulate negative emotions. By doing so, athletes may improve their sport-related coping skills, and thereby enhance athletic performance. PMID- 28989552 TI - Inflexible Youngsters: Psychological and Psychopathological Correlates of the Avoidance and Fusion Questionnaire for Youths in Nonclinical Dutch Adolescents. AB - The present study examined psychological and psychopathological correlates of psychological inflexibility as measured by the Avoidance and Fusion Questionnaire for Youth (AFQ-Y) in two independent samples of nonclinical Dutch adolescents aged between 12 and 18 years (Ns being 184 and 157). Participants completed a survey containing the AFQ-Y and scales assessing mindfulness, thought suppression, self-compassion, self-worth, self-efficacy, and internalizing/externalizing symptoms. In both samples, the AFQ-Y was found to be a reliable measure of psychological inflexibility that correlated in a theoretically meaningful way with other psychological constructs. Most importantly, AFQ-Y scores correlated positively with internalizing and externalizing symptoms, and in most cases, these associations remained significant when controlling for other measures. These findings suggest that psychological inflexibility is an important factor in youth psychopathology that needs to be further investigated in future research. PMID- 28989553 TI - A Randomized Controlled Pilot Intervention Study of a Mindfulness-Based Self Leadership Training (MBSLT) on Stress and Performance. AB - The present randomized pilot intervention study examines the effects of a mindfulness-based self-leadership training (MBSLT) specifically developed for academic achievement situations. Both mindfulness and self-leadership have a strong self-regulatory focus and are helpful in terms of stress resilience and performance enhancements. Based on several theoretical points of contact and a specific interplay between mindfulness and self-leadership, the authors developed an innovative intervention program that improves mood as well as performance in a real academic setting. The intervention was conducted as a randomized controlled study over 10 weeks. The purpose was to analyze the effects on perceived stress, test anxiety, academic self-efficacy, and the performance of students by comparing an intervention and control group (n = 109). Findings demonstrated significant effects on mindfulness, self-leadership, academic self-efficacy, and academic performance improvements in the intervention group. Results showed that the intervention group reached significantly better grade point averages than the control group. Moreover, the MBSLT over time led to a reduction of test anxiety in the intervention group compared to the control group. Furthermore, while participants of the control group showed an increase in stress over time, participants of the intervention group maintained constant stress levels over time. The combination of mindfulness and self-leadership addressed both positive effects on moods and on objective academic performance. The effects demonstrate the great potential of combining mindfulness with self-leadership to develop a healthy self-regulatory way of attaining achievement-related goals and succeeding in high-stress academic environments. PMID- 28989554 TI - Sexual Health Care Services among Young Adult Sexual Minority Women. AB - Young adult sexual minority women (YSMW) are at elevated risk for negative reproductive health outcomes, yet are less likely than heterosexual peers to utilize preventive health care. Medical and public health policy organizations advocate sexual orientation disclosure ("coming out") to health care providers as a strategy for increasing service utilization among YSMW. Limited research explores relationships between disclosure and receipt of sexual health services. YSMW (N=285) ages 21-24 participated in an online survey assessing their health behaviors and care utilization. We employed multivariable logistic regression models to examine the association between receipt of sexual health services and sexual orientation disclosure to provider, after adjusting for sociodemographic covariates. Thirty-five percent of YSMW were out to their provider. Less than half the sample had received Pap screening or STI testing in the previous year; approximately 15% had received at least one dose of the HPV vaccination. Disclosure was associated with increased likelihood of Pap screening (OR=2.66, p<.001) and HPV vaccination (OR=4.30, p<.001), but was not significantly associated with STI testing. Promoting coming out to providers may be a promising approach to increase sexual health care use among YSMW. Future research should explore causal relationships between these factors. PMID- 28989556 TI - Fibreglass Total Contact Casting, Removable Cast Walkers, and Irremovable Cast Walkers to Treat Diabetic Neuropathic Foot Ulcers: A Health Technology Assessment. AB - BACKGROUND: Diabetic neuropathic foot ulcers are a risk factor for lower leg amputation. Many experts recommend offloading with fibreglass total contact casting, removable cast walkers, and irremovable cast walkers as a way to treat these ulcers. METHODS: We completed a health technology assessment, which included an evaluation of clinical benefits and harms, value for money, and patient preferences for offloading devices. We performed a systematic literature search on August 17, 2016, to identify randomized controlled trials that compared fibreglass total contact casting, removable cast walkers, and irremovable cast walkers with other treatments (offloading or non-offloading) in patients with diabetic neuropathic foot ulcers. We developed a decision-analytic model to assess the cost-effectiveness of fibreglass total contact casting, removable cast walkers, and irremovable cast walkers, and we conducted a 5-year budget impact analysis. Finally, we interviewed people with diabetes who had lived experience with foot ulcers, asking them about the different offloading devices and the factors that influenced their treatment choices. RESULTS: We identified 13 randomized controlled trials. The evidence suggests that total contact casting, removable cast walkers, and irremovable cast walkers are beneficial in the treatment of neuropathic, noninfected foot ulcers in patients with diabetes but without severe peripheral arterial disease. Compared to removable cast walkers, ulcer healing was improved with total contact casting (moderate quality evidence; risk difference 0.17 [95% confidence interval 0.00-0.33]) and irremovable cast walkers (low quality evidence; risk difference 0.21 [95% confidence interval 0.01 0.40]). We found no difference in ulcer healing between total contact casting and irremovable cast walkers (low quality evidence; risk difference 0.02 [95% confidence interval -0.11-0.14]). The economic analysis showed that total contact casting and irremovable cast walkers were less expensive and led to more health outcome gains (e.g., ulcers healed and quality-adjusted life-years) than removable cast walkers. Irremovable cast walkers were as effective as total contact casting and were associated with lower costs. The 5-year budget impact of funding total contact casting, removable cast walkers, and irremovable cast walkers (device costs only at 100% access) would be $17 to $20 million per year. The patients we interviewed felt that wound healing was improved with total contact casting than with removable cast walkers, but that removable cast walkers were more convenient and came with a lower cost burden. They reported no experience or familiarity with irremovable cast walkers. CONCLUSIONS: Ulcer healing improved with total contact casting, irremovable cast walkers, and removable cast walkers, but total contact casting and irremovable cast walkers had higher rates of ulcer healing than removable cast walkers. Increased access to offloading devices could result in cost savings for the health system because of fewer amputations. Patients with diabetic foot ulcers reported a preference for total contact casting over removable cast walkers, largely because they perceived wound healing to be improved with total contact casting. However, cost, comfort, and convenience are concerns for patients. PMID- 28989555 TI - Noninvasive Evaluation of Varying Pulse Pressures in vivo Using Brachial Sphymomanometry, Applanation Tonometry, and Pulse Wave Ultrasound Manometry. AB - The routine assessment and monitoring of hypertension may benefit from the evaluation of arterial pulse pressure (PP) at more central locations (e.g. the aorta) rather solely at the brachial artery. Pulse Wave Ultrasound Manometry (PWUM) was previously developed by our group to provide direct, noninvasive aortic PP measurements using ultrasound elasticity imaging. Using PWUM, radial applanation tonometry, and brachial sphygmomanometry, this study investigated the feasibility of noninvasively obtaining direct PP measurements at multiple arterial locations in normotensive, pre-hypertensive, and hypertensive human subjects. Two-way ANOVA indicated a significantly higher aortic PP in the hypertensive subjects, while radial and brachial PP were not significantly different among the subject groups. No strong correlation (r2 < 0.45) was observed between aortic and radial/brachial PP in normal and pre-hypertensive subjects, suggesting that increases in PP throughout the arterial tree may not be uniform in relatively compliant arteries. However, there was a relatively strong positive correlation between aortic PP and both radial and brachial PP in hypertensive subjects (r2 = 0.68 and 0.87, respectively). PWUM provides a low cost, non-invasive, and direct means of measuring the pulse pressure in large central arteries such as the aorta. When used in conjunction with peripheral measurement devices, PWUM allows for the routine screening of hypertension and monitoring of BP-lowering drugs based on the PP from multiple arterial sites. PMID- 28989557 TI - ALLELE-SPECIFIC COPY NUMBER ESTIMATION BY WHOLE EXOME SEQUENCING. AB - Whole exome sequencing is currently a technology of choice in large-scale cancer genomics studies, where the priority is to identify cancer-associated variants in coding regions. We describe a method for estimating allele-specific copy number using whole exome sequencing data from tumor and matched normal. PMID- 28989558 TI - Designing penalty functions in high dimensional problems: The role of tuning parameters. AB - Various forms of penalty functions have been developed for regularized estimation and variable selection. Screening approaches are often used to reduce the number of covariate before penalized estimation. However, in certain problems, the number of covariates remains large after screening. For example, in genome-wide association (GWA) studies, the purpose is to identify Single Nucleotide Polymorphisms (SNPs) that are associated with certain traits, and typically there are millions of SNPs and thousands of samples. Because of the strong correlation of nearby SNPs, screening can only reduce the number of SNPs from millions to tens of thousands and the variable selection problem remains very challenging. Several penalty functions have been proposed for such high dimensional data. However, it is unclear which class of penalty functions is the appropriate choice for a particular application. In this paper, we conduct a theoretical analysis to relate the ranges of tuning parameters of various penalty functions with the dimensionality of the problem and the minimum effect size. We exemplify our theoretical results in several penalty functions. The results suggest that a class of penalty functions that bridges L0 and L1 penalties requires less restrictive conditions on dimensionality and minimum effect sizes in order to attain the two fundamental goals of penalized estimation: to penalize all the noise to be zero and to obtain unbiased estimation of the true signals. The penalties such as SICA and Log belong to this class, but they have not been used often in applications. The simulation and real data analysis using GWAS data suggest the promising applicability of such class of penalties. PMID- 28989560 TI - Evaluation of Performance of Introduced Yam Bean (Pachyrhizus spp.) in Three Agro Ecological Zones of Rwanda. AB - The yam bean (Pachyrizhus spp) was recently introduced as a root crop with high yield potential, considerable protein and micro-nutrient concentration to investigate its potential for food production in Rwanda. Except for Chuin types (Pachyrizhus tuberosus) which have high storage root dry matter (RDM) (26 to 36%), most accessions are consumed raw and are reported to have low RDM. The present study aimed to evaluate and identify adapted high yielding yam bean accessions in major agro-ecological zones of Rwanda. Field experiments with 22 accessions were conducted in 2012 at three research sites representing the major agro-ecologies of Rwanda. Strict reproductive pruning was followed to enhance fresh storage root yields. Across locations, ANOVA indicated highly significant differences (p < 0.01) for genotypes (G), locations (L), seasons (S) and G x L effects for storage root yield, vine yield and harvest index and accounted for 21.88%, 43.41%, 1.43% and 13.25% of the treatment sum of squares, respectively. The GGE bi-plot revealed that EC209018 is high yielding but unstable. However, genotypes, AC209034, AC209035 and EC209046, were outstanding in terms of adaptation and relative stability across the 3 locations, suggesting consistent root yields irrespective of location and environmental conditions. The GGE scatter plot showed that all genotypes formed one mega-environment for storage root yield (Karama, Musanze and Rubona) and two mega-environments for biomass yield (Karama and Rubona as one mega-environment and Musanze the second one). This study revealed that Karama is the most suitable environment for evaluation and selection of yam bean for yield components in Rwanda. PMID- 28989559 TI - Breakup-related appraisals and the psychological well-being of young adult gay and bisexual men. AB - Participation in romantic relationships during adolescence and young adulthood provides opportunities to explore one's sexuality, yet may also cause distress once these relationships dissolve. Although researchers have asserted that participation in same-sex relationships may be beneficial for young gay and bisexual men's (YGBM) psychosocial well-being, less is known about YGBM appraisals of breakups after participating in same-sex relationships. We examined the association between self-reported psychological well-being (e.g., symptoms of depression and anxiety; self-esteem, sense of personal competency) and YGBM's negative and positive appraisals of breakups within a sample of single YGBM (N=1,040; ages 18-24) who reported prior serious same-sex relationships. Negative appraisals were associated with lower psychological well-being. Positive appraisals were associated with greater anxiety symptoms, self-esteem and sense of personal competency. Our findings highlight the need to acknowledge how YGBM's differential responses to breakups may be associated with their psychological well-being. PMID- 28989561 TI - Eigenvalues of Random Matrices with Isotropic Gaussian Noise and the Design of Diffusion Tensor Imaging Experiments. AB - Tensor-valued and matrix-valued measurements of different physical properties are increasingly available in material sciences and medical imaging applications. The eigenvalues and eigenvectors of such multivariate data provide novel and unique information, but at the cost of requiring a more complex statistical analysis. In this work we derive the distributions of eigenvalues and eigenvectors in the special but important case of m*m symmetric random matrices, D, observed with isotropic matrix-variate Gaussian noise. The properties of these distributions depend strongly on the symmetries of the mean tensor/matrix, D. When D has repeated eigenvalues, the eigenvalues of D are not asymptotically Gaussian, and repulsion is observed between the eigenvalues corresponding to the same D eigenspaces. We apply these results to diffusion tensor imaging (DTI), with m = 3, addressing an important problem of detecting the symmetries of the diffusion tensor, and seeking an experimental design that could potentially yield an isotropic Gaussian distribution. In the 3-dimensional case, when the mean tensor is spherically symmetric and the noise is Gaussian and isotropic, the asymptotic distribution of the first three eigenvalue central moment statistics is simple and can be used to test for isotropy. In order to apply such tests, we use quadrature rules of order t >= 4 with constant weights on the unit sphere to design a DTI-experiment with the property that isotropy of the underlying true tensor implies isotropy of the Fisher information. We also explain the potential implications of the methods using simulated DTI data with a Rician noise model. PMID- 28989562 TI - A Bayesian approach to identify genes and gene-level SNP aggregates in a genetic analysis of cancer data. AB - Complex diseases, such as cancer, arise from complex etiologies consisting of multiple single-nucleotide polymorphisms (SNPs), each contributing a small amount to the overall risk of disease. Thus, many researchers have gone beyond single SNPs analysis methods, focusing instead on groups of SNPs, for example by analysing haplotypes. More recently, pathway-based methods have been proposed that use prior biological knowledge on gene function to achieve a more powerful analysis of genome-wide association studies (GWAS) data. In this paper we propose a novel Bayesian modeling framework to identify molecular biomarkers for disease prediction. Our method combines pathway-based approaches with multiple SNP analyses of a specified region of interest. The model's development is motivated by SNP data from a lung cancer study. In our approach we define gene-level scores based on SNP allele frequencies and use a linear modeling setting to study the scores association to the observed phenotype. The basic idea behind the definition of gene-level scores is to weigh the SNPs within the gene according to their rarity, based on genotype frequencies expected under the Hardy-Weinberg equilibrium law. This results in scores giving more importance to the unusually low frequencies, i.e. to SNPs that might indicate peculiar genetic differences between subjects belonging to different groups. An additional feature of our approach is that we incorporate information on SNP-to-SNP associations into the model. In particular, we use network priors that model the linkage disequilibrium between SNPs. For posterior inference, we design a stochastic search method that identifies significant biomarkers (genes and SNPs) for disease prediction. We assess performances on simulated data and compare results to existing approaches. We then show the ability of the proposed methodology to detect relevant genes and associated SNPs in a lung cancer dataset. PMID- 28989563 TI - GENERATIVE METHOD TO DISCOVER EMPHYSEMA SUBTYPES WITH UNSUPERVISED LEARNING USING LUNG MACROSCOPIC PATTERNS (LMPS): THE MESA COPD STUDY. AB - Pulmonary emphysema overlaps considerably with chronic obstructive pulmonary disease (COPD), and is traditionally subcategorized into three subtypes: centrilobular emphysema (CLE), panlobular emphysema (PLE) and paraseptal emphysema (PSE). Automated classification methods based on supervised learning are generally based upon the current definition of emphysema subtypes, while unsupervised learning of texture patterns enables the objective discovery of possible new radiological emphysema subtypes. In this work, we use a variant of the Latent Dirichlet Allocation (LDA) model to discover lung macroscopic patterns (LMPs) in an unsupervised way from lung regions that encode emphysematous areas. We evaluate the possible utility of the LMPs as potential novel emphysema subtypes via measuring their level of reproducibility when varying the learning set and by their ability to predict traditional radiological emphysema subtypes. Experimental results show that our algorithm can discover highly reproducible LMPs, that predict traditional emphysema subtypes. PMID- 28989565 TI - Risk of liver disease in methotrexate treated patients. AB - Methotrexate is the first line drug treatment for a number of rheumatic and non rheumatic diseases. It is effective in controlling disease activity and preventing disease-related damage, and significantly cheaper than many alternatives. Use in rheumatoid arthritis infers a significant morbidity and mortality benefit. Methotrexate is generally well tolerated but can cause symptomatic adverse events. Multiple serious adverse events have been attributed to methotrexate, based largely on older reports using high or daily doses, and subsequent case reports and circumstantial evidence. The risk with modern dosing regimens: Lower doses, weekly schedules, and concomitant folic acid is less clear. Clarification and dissemination of the actual risk is crucial so appropriate judgements can be made for patients who may benefit from this treatment. Methotrexate has been associated with a range of liver related adverse events ranging from asymptomatic transaminase elevations to fibrosis and fatal hepatic necrosis. Concern over potential liver toxicity has resulted in treatment avoidance, cessation, or recommendations for investigations which may be costly, invasive and unwarranted. Modern laboratory monitoring of liver blood tests may also influence the risk of more serious complications. The majority of present day studies report an approximate doubling of the relative risk of elevated transaminases in methotrexate treated patients but no increased risk of symptomatic or severe liver related adverse events. In this article we will review the evidence around methotrexate and liver related adverse events. PMID- 28989564 TI - Diffusion weighted magnetic resonance imaging of liver: Principles, clinical applications and recent updates. AB - Diffusion-weighted imaging (DWI), a functional imaging technique exploiting the Brownian motion of water molecules, is increasingly shown to have value in various oncological and non-oncological applications. Factors such as the ease of acquisition and ability to obtain functional information in the absence of intravenous contrast, especially in patients with abnormal renal function, have contributed to the growing interest in exploring clinical applications of DWI. In the liver, DWI demonstrates a gamut of clinical applications ranging from detecting focal liver lesions to monitoring response in patients undergoing serial follow-up after loco-regional and systemic therapies. DWI is also being applied in the evaluation of diffuse liver diseases such as non-alcoholic fatty liver disease, hepatic fibrosis and cirrhosis. In this review, we intend to review the basic principles, technique, current clinical applications and future trends of DW-MRI in the liver. PMID- 28989566 TI - Regional differences in genetic susceptibility to non-alcoholic liver disease in two distinct Indian ethnicities. AB - AIM: To validate the association of variants in PNPLA3 (rs2281135) and TM6SF2 (rs58542926) genes with ultrasound detected non-alcoholic fatty liver disease (NAFLD). METHODS: A total of 503 individuals with and without fatty infiltration were recruited. Fatty infiltration was confirmed based on ultrasound findings. Anthropometric data and blood samples were collected from the study group. DNA was isolated from peripheral blood, quality and quantity was assessed by gel electrophoresis and spectrophotometer respectively. Genotyping of the variants in PNPLA3 and TM6SF2 genes was carried out by employing taqman probes (C_15875080_10 for PNPLA3 and C_8946351_10 for TM6SF2 SNP) on real time PCR (Stepone Lifetechnologies). Genotype data was tested for deviations from Hardy-Weinberg equilibrium. chi2 test was used to analyze the statistical significance of the difference in genotype distribution of the studied variants in patients and controls and the strength of association was expressed as odds ratio (95%CI). A two-tailed P value of <= 0.05 was considered statistically significant. RESULTS: The study group comprised of 503 individuals of which 256 had fatty infiltration and 247 without fatty infiltration and thus formed the patient and control groups respectively. As the patient group could be divided in to two distinct ethnicities (ancestral South Indians-ASI and North-East Indians-NEI), further recruitment of control cohort and association analyses was carried out based on ethnicities. Of the 256 with fatty infiltration 93 were ASI and 163 were NEI and of the 247 controls 138 were ASI and 109 were NEI. As expected, there were significant differences in the anthropometric and other clinical data between the control and the patient groups. However significant differences within the ethnicities were also noted. While rs2281135 in PNPLA3 gene was significantly associated (P = 0.03) with higher risk (odds 1.9, 95%CI: 1.5-3.14, P = 0.03) of NAFLD in NEI ethnicity, rs58542926 in TM6SF2 gene was significantly associated with NAFLD with a 2.7 fold higher risk (odds 2.7, 95%CI: 1.37-5.3, P = 0.0004) of the disease. There were significantly higher proportions of individuals with variants in both the genes in the patient group in both ASI (patients - 14/93 and controls - 7/138; P = 0.009) and NEI ethnicities (patients - 17/163 and controls 7/109; P = 0.01). CONCLUSION: Although the study identified distinct genetic susceptibility in the two ethnicities, transheterozygosity of the variants suggests higher risk of NAFLD in individuals with both the variants. PMID- 28989567 TI - Conjugated hyperbilirubinemia presenting in first fourteen days in term neonates. AB - AIM: To describe the etiology and characteristics of early-onset conjugated hyperbilirubinemia (ECHB) presenting within 14 d of life in term neonates. METHODS: Retrospective review was performed of term infants up to 28-d-old who presented with conjugated hyperbilirubinemia (CHB) at a tertiary center over a 5 year period from January 2010 to December 2014. CHB is defined as conjugated bilirubin (CB) fraction greater than 15% of total bilirubin and CB greater or equal to 25 MUmol/L. ECHB is defined as CHB detected within 14 d of life. "Late onset" CHB (LCHB) is detected at 15-28 d of life and served as the comparison group. RESULTS: Total of 117 patients were recruited: 65 had ECHB, 52 had LCHB. Neonates with ECHB were more likely to be clinically unwell (80.0% vs 42.3%, P < 0.001) and associated with non-hepatic causes (73.8% vs 44.2%, P = 0.001) compared to LCHB. Multifactorial liver injury (75.0%) and sepsis (17.3%) were the most common causes of ECHB in clinically unwell infants, majority (87.5%) had resolution of CHB with no progression to chronic liver disease. Inborn errors of metabolism were rare (5.8%) but associated with high mortality (100%) in our series. In the subgroup of clinically well infants (n = 13) with ECHB, biliary atresia (BA) was the most common diagnosis (61.5%), all presented initially with normal stools and decline in total bilirubin but with persistent CHB. CONCLUSION: Secondary hepatic injury is the most common reason for ECHB. BA presents with ECHB in well infants without classical symptoms of pale stools and deep jaundice. PMID- 28989568 TI - Expression of matrix metalloproteinase-11 is increased under conditions of insulin resistance. AB - AIM: To investigate matrix metalloproteinase-11 (MMP-11) expression in adipose tissue dysfunction, using in vitro and in vivo models of insulin resistance. METHODS: Culture of mouse 3T3-L1 preadipocytes were induced to differentiation into mature 3T3-L1 adipocytes. Cellular insulin resistance was induced by treating differentiated cultured adipocytes with hypoxia and/or tumor necrosis factor (TNF)-alpha, and transcriptional changes were analyzed in each condition thereafter. For the in vivo studies, MMP-11 expression levels were measured in white adipose tissue (WAT) from C57BL/6J mice that underwent low fat diet or high fat feeding in order to induce obesity and obesity-related insulin resistance. Statistical analysis was carried out with GraphPad Prism Software. RESULTS: MMP 11 mRNA expression levels were significantly higher in insulin resistant 3T3-L1 adipocytes compared to control cells (1.46 +/- 0.49 vs 0.83 +/- 0.21, respectively; P < 0.00036). The increase in MMP-11 expression was observed even in the presence of TNF-alpha alone (3.79 +/- 1.11 vs 1 +/- 0.17, P < 0.01) or hypoxia alone (1.79 +/- 0.7 vs 0.88 +/- 0.1, P < 0.00023). The results obtained in in vitro experiments were confirmed in the in vivo model of insulin resistance. In particular, MMP-11 mRNA was upregulated in WAT from obese mice compared to lean mice (5.5 +/- 2.8 vs 1.1 +/- 0.7, respectively; P < 3.72E-08). The increase in MMP-11 levels in obese mice was accompanied by the increase in typical markers of fibrosis, such as collagen type VI alpha 3 (Col6alpha3), and fibroblast-specific protein 1. CONCLUSION: Our results indicate that dysregulation of MMP-11 expression is an early process in the adipose tissue dysfunction, which leads to obesity and obesity-related insulin resistance. PMID- 28989569 TI - Clinical profile of diabetes at diagnosis among children and adolescents at an endocrine clinic in Ghana. AB - AIM: To determine the clinical features of diabetes in children and adolescents in Ghana. METHODS: Retrospective review of clinical features of all children and adolescents with new-onset diabetes seen at the paediatric endocrinology clinic of Komfo Anokye Teaching Hospital in Kumasi, from February 2012 to Auguest 2016. RESULTS: One hundred and six subjects presented with diabetes. Ninety (84.9%) were diagnosed by clinical features and family history as type 1, and 16 (15.1%) type 2. For type 1 subjects, age range at diagnosis was 0.9-19.9 year (y), peak age of onset 12-13 year, and 3.3% were < 5 year, 21.1% 5- < 10 year, 45.6% 10- < 15 year and 30.0% 15- < 20 year. Seventy-one point one percent were female. Common clinical features were polyuria (100%), polydipsia (98.9%), and weight loss (82.2%). Mean BMI SD was -0.54, range -3.84 to 2.47. 60.0% presented in diabetic ketoacidosis (DKA). Nine had infections at onset (skin, abscess, leg ulcer). Mean +/- SD HbA1c at diagnosis was 12.7% +/- 1.9% (115 +/- 21 mmol/mol). Four have since died: Hypoglycaemia (2), recurrent DKA (1), osteosarcoma (1). Two other type 1 cases died of DKA at presentation in emergency before being seen by the paediatric endocrinologist. Crude mortality rate including these 2 cases was 32.2/1000 patient years. Type 2 cases were 81% female, age of onset 9-19 year. Mean BMI SD was 1.49, range -0.87 to 2.61. Forty-three point eight percent presented in DKA. All type 2 cases had acanthosis nigricans. Overall, 9.8% did not have home refrigeration, most using clay pot evaporative cooling for insulin storage. CONCLUSION: Type 1 occurs with a female preponderance and high DKA rates. Type 2 also occurs. Typology based on clinical features is difficult. Community and professional awareness is warranted. PMID- 28989570 TI - Eye and foot checks in patients with diabetes on haemodialysis: Are they done, and who does them? AB - AIM: To determine if retinal and foot checks are carried out on patients with diabetes receiving haemodialysis. METHODS: Eighty-four patients with diabetes receiving haemodialysis were asked if they recalled having eye and foot screening in the last year, and if so, by whom was the check done. RESULTS: Seventy-seven (91.7%) patients recalled having an eye check in the preceding 12 mo. Of these, 52 (67.5%) did so in an ophthalmology clinic, 17 (22%) in retinal screening, three (3.9%) in an optician clinic. Three patients (3.9%) went to both ophthalmology and retinal screening, and two (2.6%) attended an ophthalmology and optician. Seventy (83.3%) patients recalled having a foot check in the preceding 12 mo. Of these, 33 (47.1%) were done by practice nurse, 14 (20%) by a diabetes nurse, 11 (15.7%) by a general practitioner, eight (11.4%) by a chiropodist, and four (5.7%) were each checked by renal nurse, diabetes consultant, junior doctor, or unknown person at a foot clinic. CONCLUSION: Most patients with diabetes on haemodialysis are able to recall having an eye check in the last year, although 8.3% could not. A significant proportion of patients could not recall having a foot check (16.7%) in the last year. This baseline audit suggests that an improvement in the rate of foot screening is important to achieve in patients with diabetes on haemodialysis in our unit. PMID- 28989571 TI - Black soybean anthocyanins attenuate inflammatory responses by suppressing reactive oxygen species production and mitogen activated protein kinases signaling in lipopolysaccharide-stimulated macrophages. AB - BACKGROUND/OBJECTIVES: Oxidative stress is closely related with inflammation and development of many diseases. Black soybean seed coat contains high amount of anthocyanins, which are well-known for free radical scavenging activities. This study investigated inflammatory response and action mechanism of black soybean anthocyanins with regard to antioxidant activity in lipopolysaccharide (LPS) stimulated RAW 264.7 cells. MATERIALS/METHODS: RAW 264.7 cells were treated with anthocyanins extracted from black soybean seed coats in a concentration range of 12.5 to 100 ug/mL. The production of reactive oxygen species (ROS), secretion of pro-inflammatory mediators and cytokines, and the signaling in the mitogen activated protein kinases (MAPKs) pathway were examined. RESULTS: Black soybean anthocyanins significantly decreased LPS-stimulated production of ROS, inflammatory mediators such as nitric oxide (NO) and prostaglandin E2, and pro inflammatory cytokines, including tumor necrosis factor alpha and interleukin-6, in a dose-dependent manner without cytotoxicity (P < 0.001). Black soybean anthocyanins downregulated the expression of inducible NO synthase and cyclooxygenase-2 in LPS-stimulated RAW 264.7 cells (P < 0.001). Moreover, black soybean anthocyanins inhibited LPS-induced phosphorylation of MAPKs, including extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 (P < 0.001). CONCLUSION: These results suggest that black soybean anthocyanins exert anti-inflammatory activity by inhibiting ROS generation and subsequent MAPKs signaling, thereby inhibiting inflammatory responses. PMID- 28989572 TI - Effects of ingredients of Korean brown rice cookies on attenuation of cholesterol level and oxidative stress in high-fat diet-fed mice. AB - BACKGROUND/OBJECTIVES: Owing to health concerns related to the consumption of traditional snacks high in sugars and fats, much effort has been made to develop functional snacks with low calorie content. In this study, a new recipe for Korean rice cookie, dasik, was developed and its antioxidative, lipid-lowering, and anti-inflammatory effects and related mechanisms were elucidated. The effects were compared with those of traditional rice cake dasik (RCD), the lipid-lowering effect of which is greater than that of traditional western-style cookies. MATERIALS/METHODS: Ginseng-added brown rice dasik (GBRD) was prepared with brown rice flour, fructooligosaccharide, red ginseng extract, and propolis. Mice were grouped (n = 7 per group) into those fed a normal AIN-76 diet, a high-fat diet (HFD), and HFD supplemented with RCD or GBRD. Dasik in the HFD accounted for 7% of the total calories. The lipid, reactive oxygen species, and peroxynitrite levels, and degree of lipid peroxidation in the plasma or liver were determined. The expression levels of proteins involved in lipid metabolism and inflammation, and those of antioxidant enzymes were determined by western blot analysis. RESULTS: The plasma and hepatic total cholesterol concentrations in the GBRD group were significantly decreased via downregulation of sterol regulatory element-binding protein-2 and 3-hydroxy-3-methylglutaryl-CoA reductase (P < 0.05). The hepatic peroxynitrite level was significantly lower, whereas glutathione was higher, in the GBRD group than in the RCD group. Among the antioxidant enzymes, catalase (CAT) and glutathione peroxidase (GPx) were significantly upregulated in the GBRD group (P < 0.05). In addition, nuclear factor-kappaB (NF-kappaB) expression in the GBRD group was significantly lower than that in the RCD group. CONCLUSIONS: GBRD decreases the plasma and hepatic cholesterol levels by downregulating cholesterol synthesis. This new dasik recipe also improves the antioxidative and anti-inflammatory status in HFD-fed mice via CAT and GPx upregulation and NF-kappaB downregulation. These effects were significantly higher than those of RCD. PMID- 28989574 TI - Protection of the brain through supplementation with larch arabinogalactan in a rat model of vascular dementia. AB - BACKGROUND/OBJECTIVES: Vascular dementia (VaD) caused by reduced blood supply to the brain manifests as white matter lesions accompanying demyelination and glial activation. We previously showed that arabinoxylan consisting of arabinose and xylose, and arabinose itself attenuated white matter injury in a rat model of VaD. Here, we investigated whether larch arabinogalactan (LAG) consisting of arabinose and galactose could also reduce white matter injury. MATERIALS/METHODS: We used a rat model of bilateral common carotid artery occlusion (BCCAO), in which the bilateral common carotid arteries were exposed and ligated permanently with silk sutures. The rats were fed a modified AIN-93G diet supplemented with LAG (100 mg/kg/day) for 5 days before and 4 weeks after being subjected to BCCAO. Four weeks after BCCAO, the pupillary light reflex (PLR) was measured to assess functional consequences of injury in the corpus callosum (cc). Additionally, Luxol fast blue staining and immunohistochemical staining were conducted to assess white matter injury, and astrocytic and microglial activation, respectively. RESULTS: We showed that white matter injury in the the cc and optic tract (opt) was attenuated in rats fed diet supplemented with LAG. Functional consequences of injury reduction in the opt manifested as improved PLR. Overall, these findings indicate that LAG intake protects against white matter injury through inhibition of glial activation. CONCLUSIONS: The results of this study support our hypothesis that cell wall polysaccharides consisting of arabinose are effective at protecting white matter injury, regardless of their origin. Moreover, LAG has the potential for development as a functional food to prevent vascular dementia. PMID- 28989573 TI - Corn silk extract improves benign prostatic hyperplasia in experimental rat model. AB - BACKGROUND/OBJECTIVES: This study was conducted to investigate the effect of a corn silk extract on improving benign prostatic hyperplasia (BPH). MATERIALS/METHODS: The experimental animals, 6-week-old male Wistar rats, were divided into sham-operated control (Sham) and experimental groups. The experimental group, which underwent orchiectomy and received subcutaneous injection of 10 mg/kg of testosterone propionate to induce BPH, was divided into a Testo Only group that received only testosterone, a Testo+Fina group that received testosterone and 5 mg/kg finasteride, a Testo+CSE10 group that received testosterone and 10 mg/kg of corn silk extract, and a Testo+CSE100 group that received testosterone and 100 mg/kg of corn silk extract. Prostate weight and concentrations of dihydrotestosterone (DHT), 5alpha-reductase 2 (5alpha-R2), and prostate specific antigen (PSA) in serum or prostate tissue were determined. The mRNA expressions of 5alpha-R2 and proliferating cell nuclear antigen (PCNA) in prostate tissue were also measured. RESULTS: Compared to the Sham group, prostate weight was significantly higher in the Testo Only group and decreased significantly in the Testo+Fina, Testo+CSE10, and Testo+CSE100 groups (P < 0.05), results that were consistent with those for serum DHT concentrations. The concentrations of 5alpha-R2 in serum and prostate as well as the mRNA expression of 5alpha-R2 in prostate were significantly lower in the Testo+Fina, Testo+CSE10, and Testo+CSE100 groups than that in the Testo Only group (P < 0.05). Similarly, the concentrations of PSA in serum and prostate were significantly lower in the Testo+Fina, Testo+CSE10, and Testo+CSE100 groups (P < 0.05) than in the Testo Only group. The mRNA expression of PCNA in prostate dose-independently decreased in the Testo+CSE-treated groups (P < 0.05). CONCLUSIONS: BPH was induced through injection of testosterone, and corn silk extract treatment improved BPH symptoms by inhibiting the mRNA expression of 5alpha-R2 and decreasing the amount of 5alpha-R2, DHT, and PSA in serum and prostate tissue. PMID- 28989575 TI - Antihypertensive effect of Ganjang (traditional Korean soy sauce) on Sprague Dawley Rats. AB - BACKGROUND/OBJECTIVES: Although Korean fermented foods contain large amounts of salt, which is known to exacerbate health problems, these foods still have beneficial effects such as anti-hypertension, anti-cancer, and anti-colitis properties. We hypothesized that ganjang may have different effects on blood pressure compared to same concentrations of salt. MATERIALS/METHODS: Sprague Dawley rats were divided into control (CT), NaCl (NC), and ganjang (GJ) groups and orally administered with 8% NaCl concentration for 9 weeks. The systolic blood pressure (SBP), serum chemistry, Na+ and K+ concentrations and renal gene expressions were measured. RESULTS: The SBP was significantly increased in the NC group compared to the GJ and CT groups. In addition, the Na+ concentration in urine was higher in the GJ and NC groups than the CT group, but the urine volume was increased in the GJ group compared to the other groups. The serum renin levels were decreased in the GJ group compared to the CT group, while the serum aldosterone level was decreased in the GJ group relative to the NC group. The mRNA expression of the renin, angiotensin II type I receptor, and mineralocorticoid receptor were significantly lower in the GJ group compared to other groups. Furthermore, GJ group showed the lowest levels of genes for Na+ transporter in kidney cortex such as Na+/K+ ATPasealpha1 (NKAalpha1), Na+/H+ exchanger 3 (NHE3), Na+/HCO3- co-exchanger (NBC), and carbonic anhydrases II (CAII). CONCLUSIONS: The decreased SBP in the GJ could be due to decreased renin and aldosterone levels in serum and increased urinary volume and excretion of Na+ with its transporter gene alteration. Therefore, ganjang may have antihypertensive effect despite its high contents of salt. PMID- 28989576 TI - Antihypertensive effect of an enzymatic hydrolysate from Styela clava flesh tissue in type 2 diabetic patients with hypertension. AB - BACKGROUND/OBJECTIVES: In this randomized, placebo-controlled, double-blind study, we evaluated the antihypertensive effects of enzymatic hydrolysate from Styela clava flesh tissue in patients with type 2 diabetes mellitus (T2DM) and hypertension. SUBJECTS/METHODS: S. clava flesh tissue hydrolysate (SFTH) (n = 34) and placebo (n = 22) were randomly allocated to the study subjects. Each subject ingested two test capsules (500 mg) containing powdered SFTH (SFTH group) or placebo capsules (placebo group) during four weeks. RESULTS: In the SFTH group, systolic and diastolic blood pressure decreased significantly 4 weeks after ingestion by 9.9 mmHg (P < 0.01) and 7.8 mmHg (P < 0.01), respectively. In addition, the SFTH group exhibited a significant decrease in hemoglobin A1c with a tendency toward improvement in homeostasis model assessment of insulin resistance, triglyceride, apolipoprotein B and plasma insulin levels after 4 weeks. No adverse effects were observed in other indexes, including biochemical and hematological parameters in both groups. CONCLUSION: The results of our study suggested that SFTH exerts a regulatory, antihypertensive effect in patients with T2DM and hypertension. PMID- 28989577 TI - Creating a school nutrition environment index and pilot testing it in elementary and middle schools in urban South Korea. AB - BACKGROUND/OBJECTIVES: The role of a school's nutrition environment in explaining students' eating behaviors and weight status has not been examined in an Asian setting. The purpose of this study was to create a school nutrition environment index and to pilot test the index in elementary and middle schools in urban South Korea. SUBJECTS/METHODS: This study used a mixed-methods approach. Environment assessment tools were developed based on formative research, which comprised literature reviews, in-depth interviews, and focus group discussions. Key elements from the formative research were included in the assessment tool, which consisted of a structured survey questionnaire for school dietitians. Fifteen school dietitians from 7 elementary and 8 middle schools in Seoul completed the questionnaire. RESULTS: The formative research revealed four main sections that guided a summary index to assess a school's nutrition environment: resource availability, education and programs, dietitians' perceptions and characteristics, and school lunch menu. Based on the literature reviews and interviews, an index scoring system was developed. The total possible score from the combined four index sections was 40 points. From the 15 schools participating in the pilot survey, the mean school nutrition-environment index was 22.5 (standard deviation +/- 3.2; range 17-28). The majority of the schools did not offer classroom-based nutrition education or nutrition counseling for students and parents. The popular modes of nutrition education were school websites, posters, and newsletters. CONCLUSIONS: This paper illustrates the process used to develop an instrument to assess a school's nutrition environment. Moreover, it presents the steps used to develop a scoring system for creation of a school nutrition environment index. As pilot testing indicated the total index score has some variation across schools, we suggest applying this instrument in future studies involving a larger number of schools. Future studies with larger samples will allow investigation of the validity and reliability of this newly developed tool. PMID- 28989578 TI - Chia seed (Salvia Hispanica L.) added yogurt reduces short-term food intake and increases satiety: randomised controlled trial. AB - BACKGROUND/OBJECTIVES: Several studies have reported that consumption of Salvia Hispanica L.,commonly known as chia seed, may exert beneficial effects on health outcomes. The main purpose of this study was to examine the influence of chia seed consumption as a mid-morning snack on short-term satiety. SUBJECTS/METHODS: Subjects (n = 24) were tested using a randomized, cross-over design consisting of three mid-morning snacks. Yogurt with no chia seed, yogurt with 7 g chia seed, and yogurt with 14 g chia seed were given to subjects on different test days. After subjects were asked to report visual analog scale (VAS) scores on sensory outcomes, ad libitum lunch was served, and energy intake of individuals was measured. RESULTS: VAS scores indicated that participants reported significantly lower scores for hunger (P = 0.033), prospective food consumption (P = 0.031), amounts of food that could be consumed (P = 0.017), desire for sugary foods (P = 0.015), and higher scores for satiety (P = 0.031) on the test days with 7 g and 14 g chia seed. Energy intake of individuals during ad libitum lunch was significantly lower when they consumed yogurt with 7 g or 14 g chia seed (P = 0.037). CONCLUSIONS: The study demonstrated that chia seed consumption as a mid morning snack may induce short-term satiety in healthy individuals. PMID- 28989579 TI - Circulating folate levels and colorectal adenoma: a case-control study and a meta analysis. AB - BACKGROUND/OBJECTIVES: The relationship between folate and colorectal neoplasia remains controversial. We examined the association between serum folate concentrations and colorectal adenomas in a case-control study of Korean adults and conducted a meta-analysis. SUBJECTS/METHODS: Our case-control study included 113 pairs of case and control who underwent colonoscopy and provided blood samples. We used multivariable conditional logistic regression models to obtain the odds ratios and 95% confidence interval (CIs). For meta-analysis, we identified the relevant studies by searching the PubMed database up to February 2017, included our case-control study and combined the study-specific relative risks (RRs) using a random-effects model. RESULTS: In this case-control study, we included 58 men and 55 women with colorectal adenomas and sex and fasting status matched the controls. We did not find any significant association between the serum folate levels and colorectal adenomas in either men or women. For meta analysis, a total of eleven studies were included in our analysis and classified into two groups; polyp clearance group (PC) for the studies that included participants who underwent endoscopies and had their polyps removed at baseline; and no polyp clearance group (NPC) for the studies that included participants whose histories of endoscopies were unknown or who underwent their first endoscopies. Four PC (1,311 cases and 1,672 non-cases) and eight NPC studies (3,501 cases and 11,347 non-cases) were included. The combined RRs (95% CIs) comparing the bottom with the top categories of circulating folate levels were 1.07 (0.97-1.18) for the NPC group but 1.45 (1.16-1.74) for the PC group. CONCLUSIONS: Low circulating folate levels were associated with new adenoma formation. PMID- 28989580 TI - Luteolin and fisetin suppress oxidative stress by modulating sirtuins and forkhead box O3a expression under in vitro diabetic conditions. AB - BACKGROUND/OBJECTIVE: Chronic hyperglycemia induces oxidative stress via accumulation of reactive oxygen species (ROS) and contributes to diabetic complications. Hyperglycemia induces mitochondrial superoxide anion production through the increased activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. This study aimed to determine whether fisetin and luteolin treatments suppress the oxidative stress by modulating the expression of sirtuins (SIRTs) and forkhead box O3a (FOXO3a) under hyperglycemic conditions in human monocytes. MATERIALS/METHODS: Human monocytic cells (THP-1) were cultured under osmotic control (14.5 mmol/L mannitol), normoglycemic (NG, 5.5 mmol/L glucose), or hyperglycemic (HG, 20 mmol/L glucose) conditions, in the absence or presence of fisetin and luteolin for 48 h. To determine the effect of fisetin and luteolin treatments on high glucose-induced oxidative stress, western blotting and intracellular staining were performed. RESULTS: Hyperglycemic conditions increased the ROS production, as compared to normoglycemic condition. However, fisetin and luteolin treatments inhibited ROS production under hyperglycemia. To obtain further insight into ROS production in hyperglycemic conditions, evaluation of p47phox expression revealed that fisetin and luteolin treatments inhibited p47phox expression under hyperglycemic conditions. Conversely, the expression levels of SIRT1, SIRT3, SIRT6, and FOXO3a were decreased under high glucose conditions compared to normal glucose conditions, but exposure to fisetin and luteolin induced the expression of SIRT1, SIRT3, SIRT6, and FOXO3a. The above findings suggest that fisetin and luteolin inhibited high glucose-induced ROS production in monocytes through the activation of SIRTs and FOXO3a. CONCLUSIONS: The results of our study supports current researches that state fisetin and luteolin as potential agents for the development of novel strategies for diabetes. PMID- 28989581 TI - Erratum: Effects of disturbed liver growth and oxidative stress of high-fat diet fed dams on cholesterol metabolism in offspring mice. AB - [This corrects the article on p. 386 in vol. 10, PMID: 27478544.]. PMID- 28989582 TI - Patterns of DNMT1 Promoter Methylation in Patients with Acute Lymphoblastic Leukemia. AB - Background: Acute lymphoblastic leukemia (ALL) is a clonal malignant disorder characterized by an uncontrolled proliferation of immature T or B lymphocytes. Extensive studies have shown that the epigenetic changes, especially modified DNA methylation patterns in the regulatory regions through the DNA methyltransferase (DNMTs), play an important role in the development of genetic disorders and abnormal growth and maturation capacity of leukemic stem cells (LSCs).The aim of this study was to evaluate the changes in DNMT1 promoter methylation and its expression pattern in patients with ALL. Materials and Methods: In this experimental study, methylation specific PCR (MSP) was used to assess the methylation status of DNMT1 promoter regions in samples collected from ALL patients (n=45) and healthy control subjects. According to this method, un methylated cytosine nucleotides are converted to uracil by sodium bisulfite and the proliferation of methylated and un-methylated regions are performed using specific primers for target sequences. Results: None of the patients with B and T ALL showed methylated promoter regions of the DNMT1 gene, while the methylation pattern of both pre-B ALL patients and the control group showed a relative promoter methylation. Conclusion: Analysis of promoter methylation patterns in various subgroups of ALL has revealed the importance of DNMT1 in the regulation of gene expression. Likewise, extensive data have also highlighted the methylation-based mechanisms exerted by DNAM1 as one of the main participants regulating gene expression in B-ALL and T-ALL patients. Investigation of the overall DNA methylation pattern offers significant improvements in the prediction of disease prognosis and treatment response. PMID- 28989584 TI - Expression Analysis of Long Non-Coding PCAT-1in Breast Cancer. AB - Background: The prostate cancer-associated non-coding RNA transcript 1 (PCAT-1) is a newly identified long non- coding RNA whose participation in tumorigenesis of a variety of cancers has been observed. In the present study, we aimed at analysis of its expression in breast cancer patients. Materials and Methods: The expression of PCAT-1 was assessed using real-time reverse transcription polymerase chain reaction in tumor samples obtained from 47newly diagnosed breast cancer patients as well as their corresponding adjacent non-cancerous tissues (ANCTs). Results: We detected significant over-expression of PCAT-1 in 12/47 (25.5%) of tumoral tissues compared with their corresponding ANCTs. However, no significant association has been found between the levels of PCAT-1 transcripts and patients' clinical data such as tumor size, stage, grade, estrogen and progesterone receptors or Her2/neu status. Conclusion: PCAT-1 is possibly involved in the pathogenesis of fraction of breast cancers. Future studies are needed to evaluate its precise function in breast cancer. PMID- 28989583 TI - Attitudes toward Telling the Truth to Cancer Patients in Iran: A Review Article. AB - Background:Patients generally have the right to be informed of their condition, but the debate over the issue of truth disclosure is still present. The attempt of this study is to review the approaches toward truth- telling to cancer patients in Iran. Materials and Methods: This study is a narrative review that included articles published in Iran on attitudes toward telling the truth to cancer patients. The present study extracted data from articles published in PubMed, Science Direct, Scientific Information Database (SID), Magiran, Iran Medex, Google Scholar, Iranian Research Institute for Information Science and Technology with key terms such as truth disclosure, breaking bad news, death awareness and disclosure of diagnosis without any time restriction. Results: Totally, 21 articles including 14 in English and 7 in Persian were selected and reviewed. The results of the study have shown that although treatment team and caregivers are unwilling to disclose the truth to patients, they have a tendency to obtain more information about their disease. Conclusion: As the incidence of cancer has increased worldwide, telling the truth to patients seeking more information about cancer disease would be inevitable, but more studies are required to provide scientific procedures based on evidence for truth disclosure, not the whole, to cancer patients. PMID- 28989585 TI - Absolute and Functional Iron Deficiency Anemia among Different Tumors in Cancer Patients in South Part of Iran, 2014. AB - Background: Anemia is a common problem in cancer patients. This study aimed to investigate the frequency rate of absolute and functional iron deficiency anemia among different tumors and its distribution in different stages of cancer in solid tumors. Materials and Methods: This study was performed on 597 patients with cancer referred to Ali-Ebne-Abitaleb Hospital in Zahedan. Laboratory tests included serum iron, transferrin saturation, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and complete blood count (CBC). The malignancy type and stages were recorded. Data were analysed using SPSS statistics software (Ver.19). Results: Four hundred and fifty-seven patients (76.5 %) diagnosed with solid tumors and 140 (23.5%) suffered from hematologic malignancies. Among patients with solid tumors, functional iron deficiency had the highest rate (300 patients had anemia and 243 (53.2%) of whom were functionally iron deficient), but in hematologic malignancies most of patients had not iron deficiency (66 patients had not iron deficiency against 12 patients had absolute iron deficiency and 62 patients had functional iron deficiency anemia) (P-value=0.021). No significant differences were observed among the various stages of cancers in terms of degrees of iron deficiency (P>0.05). Conclusion: The results of the study showed that solid tumors had a higher rate of absolute and functional iron deficiency anemia, compared to hematologic malignancies. But there was no difference between the different stages of the disease. PMID- 28989586 TI - How Do Donor-Recipient CMV Serostatus and Post-Hematopoietic Stem Cell Transplantation CMV Reactivation Affect Outcomes in Acute Leukemia Patients? AB - Background: This study evaluated CMV serostatus in donors and recipients of hematopoietic stem cell transplantation (HSCT) and its effects on CMV reactivation of patients and all aspects of CMV on HSCT outcomes. Materialsand Methods: Seven hundred and five adult acute leukemia patients (AML=408 and AML=297) who had undergone HSCT were included in this retrospective study. We categorized donor-recipient pairs in three risk groups: positive donors (D+) were studied as high-risk group, including either R+ or R-(n=485), R-D- as low-risk group (n=32) and R+D- as intermediate group (n=15). Results: There was no statistically difference in CMV reactivation among these risk groups (P=0.14).CMV infection rate was lower in R+D+ than R+D-(p=0.050). Multivariate analysis showed that patients developing CMV infection had lower overall survival (p=0.04, HR: 1.43, CI=1.00- 2.05) and higher non- relapse mortality (P=0.01, HR: 1.62, CI=1.11 2.38). Relapse rate did not change in CMV reactivated patients (P=0.94). Conclusion: The results of the study indicated that asCMV reactivation occurred more in R+D- patients compared to R+D+ ones, and was associated with inferior OS and higher NRM it could be suggested that in contrast to general belief, if the recipient is seropositive , seropositive donor is preferred to a seronegative one. PMID- 28989587 TI - High Prevalence of Vitamin D Deficiency in Newly Diagnosed Acute Myeloid Leukemia Patients and Its Adverse Outcome. AB - Background: Although several studies have supported a preventive and therapeutic role of vitamin D (Vit D) for different types of cancers, we face insufficient documentation in acute myeloid leukemia (AML). So, we examined whether the serum calcidiol (25(OH)D) levels at the time of induction therapy have any impact on response and relapse in AML patients. Materials and Methods: Blood samples were collected from 65 patients on days 0 and 28th of treatment to evaluate serum concentration of 25(OH)D and its effects on complete remission (CR) achievement, relapse rate and hospitalization length. Results: Of the 65 patients who were included in the study, 38 were male (58.5%) and 27 were female (41.5%). Median age at the time of treatment was 37 years (range 15-68). 6% of the participants were older than 60 years. In regard to 25(OH)D levels, 81.5% of AML patients were deficient (levels <20 ng/ml). There was a significant difference in CR between patients with sufficient and deficient level of 25(OH)D. Deficient patients had longer length of hospitalization than those with sufficient levels. Also Vitamin D deficient patients had higher serum ALP levels. The mean level of 25(OH)D on treatment day 28th in our study was significantly lower than the baseline value. Conclusion: The results of the study showed that serum 25(OH)D levels deficiency was highly prevalent among Iranian AML patients. Furthermore, higher Vit D levels in AML patients were associated with better outcome in these patients. PMID- 28989588 TI - Cytogenetic Abnormalities with Interphase FISH Method and Clinical Manifestation in Chronic Lymphocytic Leukemia Patients in North-East of Iran. AB - Background: Chronic lymphocytic leukemia (CLL) is one of the most prevalent adult leukemias. This malignancy is known by lymphocytosis for a duration of more than 3 months. In fact, it is a heterogeneous clinical disease with changeable progression. Chromosomal aberrations are significant parameters to predict result and survival rate and find treatment strategies for each patient. Cytogenetic methods are known as sensitive and relatively new procedures to detect abnormalities in genome. Materials and Methods: In order to identify CLL-related chromosomal abnormalities, 48 CLL patients included 38 Men and 10 Women with mean age of 58.25+/-36 were enrolled in this case series study.The survey was done at Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences. Interphase fluorescent in situ hybridization (I-FISH) was done on unstimulated peripheral blood or bone marrow samples, which were cultured in whole medium culture; it was used to detect chromosomal abnormalities such as 11q , 13q14-, 17p- , 6q- and trisomy 12 in CLL patients. Results: Analysis demonstrated that 45.5% of CLL cases had chromosomal abnormalities; 13.63% haddel 17p, 40.90% had del 13q14 and 9.09% had del 11q. Statistical analysis of data revealed a significant relevancy between age variable and splenomegaly occurrence (P value<0.05). The younger the patients were, the less the splenomegaly occurrence. Conclusion: Laboratory findings were correlated with clinical data. PMID- 28989589 TI - Aberrant Methylation of APAF-1 Gene in Acute Myeloid Leukemia Patients. AB - Background: Acute myeloid leukemia (AML) is a heterogeneous clonal disorder characterized by immature myeloid cell proliferation and bone marrow failure. Various genetic and epigenetic factors have been found to be influential in such patients. Methylation silencing of APAF-1, a putative tumor suppressor gene (TSG), has been found in several human malignancies. In this study, we explored the association of APAF-1 methylation status with AML patients. Materials and Methods: We studied the methylation status of APAF-1 gene in 101 AML patients and 50 healthy subjects as controls. Genomic DNA was extracted from leukocytes in peripheral blood or bone marrow and the methylation status of APAF-1 gene promoter was detectedusing methylation-specific PCR (MSP) method with specific methylated and unmethylated primers. Gene expression was analyzed using real time RT-PCR. Results: The prevalence of methylated (MM) and hemi-methylated (MU) CpG dinucleotides within the APAF-1 gene promoter of AML patients was 12 (11.9%) and 45 (44.6%), respectively, while no methylation was detected in the control samples (p < 0.001). Our results showed a higher frequency of methylated APAF1 in FLT3-ITD mutated cases (p=0.04). APAF1 mRNA expression was significantly lower in methylated cases compared with normal cases. Conclusion: The present study indicated the increased frequency of hypermethylation of APAF-1 gene promoter in AML patients. APAF-1 aberrant CpG island methylation was associated with transcriptional downregulation in AML patients. Therefore, promoter methylation of APAF-1 gene could be considered as an epigenetic factor that contributes to the development of AML. PMID- 28989591 TI - Familial Colorectal Cancer Type X in Central Iran: A New Clinicopathologic Description. AB - Background: Familial colorectal cancer type X (FCCX) is a subtype of mismatch repair (MMR)-proficient colorectal cancerin which the patients are clinically at risk for Lynch syndrome (LS), a common hereditary cancer predisposing syndrome. In this study, we described a new clinicopathological feature of the condition in central Iran. Materials and Methods: We designed a descriptive, retrospective study to screenat-risk colorectal cancer (CRC) patients, using Amsterdam II criteria and Molecular analysis in Isfahan (central Iran) throughout 2000-2013 period. Results: 219 early-onset (<= 50 years) CRC patients of 1659 were selected for the evaluation. Amsterdam II criteria were positive in 45 families; of whom 31 were finally analyzed by molecular testing. MMR deficiency was detected in 7/31 probands (22.6%) as affected to LS, so 24 families (77.4%) were identified as FCCX. The mean age of the probands at diagnosis among FCCX families was 45.3 years (range 24-69) versus 38.0 years (range 31-50) in LS families. The frequency of CRC among FCCX and LS families was calculated 27.9% and 67.5%, respectively. Also, the most frequent extracolonic cancer among both FCCX and LS families was stomach by 25.5% and 30.8%, respectively. Tumor site was proximal to the splenic flexure in 20.8% and 57.1% of index CRC patients in FCCX and LS families, respectively. Conclusion: Given the relative high frequency of FCCX and its different phenotype among Iranian populations, we need to set up more advanced molecular studies for exploration of unknown molecular pathways leading to tumorigenesis in this class of CRC patients. PMID- 28989590 TI - Cytogenetic Abnormalities in Myelodysplastic Syndromes: An Overview. AB - Karyotype is one of the main constituents of the International Prognostic Scoring System (IPSS) and revised-IPSS that are the cornerstones for the prognostication of patients with myelodysplastic syndromes (MDS). Del(5q), -7/del(7q), +8 and -Y are among the most extensively studied cytogenetic abnormalities in MDS. The same applies for normal karyotype. There are hundreds of other rare cytogenetic abnormalities that have been reported in MDS, included but not limited to -X, 3q abnormalities, +13/del(13q), i(17q), +21/-21. However, due to a very low number of patients, their impact on the prognosis of MDS is limited. Knowledge of the molecular consequences of different cytogenetic abnormalities allows us to modify treatment regimens based on drugs most active against the specific karyotype present, allowing for the opportunity to individualize MDS treatment and improve patient care and prognosis. PMID- 28989592 TI - Pseudohypercalcemia in Multiple Myeloma: A Case Report. AB - Hypercalcemia is a common finding in patients with multiple myeloma. Clinical manifestations of hypercalcemia correlate with the level of serum calcium. Ionized serum calcium (Ca (I)) will be increased in true hypercalcemia. In pseudohypercalcemia the Ionized Ca is normal, although binding of calcium to abnormal immunoglobulin causes increased serum calcium level. In the asymptomatic multiple myeloma patients with moderate to severe hypercalcemia, measurement of ionized calcium is critical to exclude pseudohypercalcemia. Here, we describe an asymptomatic 44-year-old man with multiple myeloma who had severe hypercalcemia, but normal serum Ionized Ca level. PMID- 28989594 TI - Feminist ecology: Doing, undoing, and redoing gender in science. AB - Women continue to be underrepresented in STEM fields and also are more likely to leave academic careers than men. While much existing sociological research on gender in science focuses on structures, institutions, and policies, we take a cultural and phenomenological approach to the question. We focus on the interaction between structural and micro-sociological forces that uphold existing gender inequalities and drive new forms of inequality within the discipline of ecology by tracing the experience of female graduate students. Ecology in the United States and elsewhere is currently undergoing three shifts, well documented by previous studies-more female scientists, interdisciplinary work, and research in human-altered landscapes-that comprise a transition to what we call "feminist ecology." We ask whether these disciplinary-level shifts in ecology are accompanied by renegotiations in the way ecologists "do gender" as they work. In this paper we argue that despite structural changes toward a feminist ecology, gender inequalities are not eliminated. Our data collected using ethnographic and autoethnographic methods during ecological fieldwork in the Northeastern United States, show that gender inequality persists through daily interactions, shaping the way that fieldwork is conducted and bodies are policed. We provide additional evidence of the way that ecologists and non-ecologists interact during fieldwork, highlighting the embeddedness of scientific disciplines within larger societal forces. Thus, the question of women in science cannot be understood strictly from within the bounds of science but extends to gender relations in society at large. We hope that this study can serve as a teaching tool for university efforts to increase the success, not just the prevalence, of women in science, and facilitate productive interdisciplinary research across disciplines. PMID- 28989593 TI - Colorectal Cancer Screening: A Comprehensive Review to Recent Non-Invasive Methods. AB - Colorectal cancer (CRC) is one of the most common cancers worldwide and considered to be one of the hassles in medical communities. CRC develops from precancerous polyps in the colon or rectum and is preventable and curable by an early diagnosis and with the removal of premalignant polyps. In recent years, scientists have looked for inexpensive and safe ways to detect CRC in its earliest stages. Strong evidence shows that screening for CRC is a crucial way to reduce the incidence and mortality of this devastating disease. The main purpose for screening is to detect cancer or pre-cancer signs in all asymptomatic patients. In this review, we holistically introduce major pathways involved in the initiation and progression of colorectal tumorgenesis, which mainly includes chromosome instability (CIN), microsatellite instability (MSI), the CpG island methylator phenotype (CIMP), and we then will discuss different screening tests and especially the latest non-invasive fecal screening test kits for the detection of CRC. PMID- 28989595 TI - Haemorrhoids: an update on management. AB - Haemorrhoids are common, affecting up to one quarter of all adults according to some estimates. Numerous interventions exist for their management, ranging from topical and medical therapies to outpatient treatments and surgical interventions that aim to fix or excise. Given the polysymptomatic nature of the disease, it is difficult to effectively judge which treatment option is best. Recently introduced novel haemorrhoid management techniques, such as stapled haemorrhoidopexy, LigasureTM excision and haemorrhoidal artery ligation, aim to reduce harm whilst maintaining or improving on outcome. These new techniques are universally more expensive, and available good quality data suggest the additional cost does not necessarily equate to universally better outcomes compared with traditional older interventions, such as rubber band ligation and excisional haemorrhoidectomy. Whatever the intervention selected for treatment, it is clear that this should be tailored to the individual based on patient choice, convenience and degree of haemorrhoids. PMID- 28989596 TI - The Automated Root Exudate System (ARES): a method to apply solutes at regular intervals to soils in the field. AB - Root exudation is a key component of nutrient and carbon dynamics in terrestrial ecosystems. Exudation rates vary widely by plant species and environmental conditions, but our understanding of how root exudates affect soil functioning is incomplete, in part because there are few viable methods to manipulate root exudates in situ. To address this, we devised the Automated Root Exudate System (ARES), which simulates increased root exudation by applying small amounts of labile solutes at regular intervals in the field.The ARES is a gravity-fed drip irrigation system comprising a reservoir bottle connected via a timer to a micro hose irrigation grid covering c. 1 m2; 24 drip-tips are inserted into the soil to 4-cm depth to apply solutions into the rooting zone. We installed two ARES subplots within existing litter removal and control plots in a temperate deciduous woodland. We applied either an artificial root exudate solution (RE) or a procedural control solution (CP) to each subplot for 1 min day-1 during two growing seasons. To investigate the influence of root exudation on soil carbon dynamics, we measured soil respiration monthly and soil microbial biomass at the end of each growing season.The ARES applied the solutions at a rate of c. 2 L m-2 week-1 without significantly increasing soil water content. The application of RE solution had a clear effect on soil carbon dynamics, but the response varied by litter treatment. Across two growing seasons, soil respiration was 25% higher in RE compared to CP subplots in the litter removal treatment, but not in the control plots. By contrast, we observed a significant increase in microbial biomass carbon (33%) and nitrogen (26%) in RE subplots in the control litter treatment.The ARES is an effective, low-cost method to apply experimental solutions directly into the rooting zone in the field. The installation of the systems entails minimal disturbance to the soil and little maintenance is required. Although we used ARES to apply root exudate solution, the method can be used to apply many other treatments involving solute inputs at regular intervals in a wide range of ecosystems. PMID- 28989597 TI - Graphene oxide-carbon nanotube hybrid assemblies: cooperatively strengthened OH...O 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 1111111111111111111111111111111111 1111111111111111111111111111111111 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 1111111111111111111111111111111111 1111111111111111111111111111111111 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 C hydrogen bonds and the removal of chemisorbed water. AB - Owing to their great significance for energy storage and sensing applications, multi-layer papers consisting of graphene oxide-carbon nanotube (GO-CNT) hybrid sheets were prepared by in situ exfoliation of graphite oxide in the presence of oxidized CNTs (oCNTs). For the first time we elucidate the influence of oCNTs on chemisorbed water (CW), i.e. the water molecules inherently bound to the oxygen functional groups (OFGs) of graphene oxide (GO) and responsible for irreversible structural damage upon thermal reduction processes. We show that oCNTs self assemble onto GO sheets during the liquid phase processing steps by forming cooperatively strengthened OH...OC hydrogen bonds between the carboxylic groups of the oCNTs and OFGs of GO. At oCNT amounts of about 10 to 15 wt% this leads to the displacement of considerable amounts of CW without altering the original chemical composition of GO. The thermally reduced GO-CNT (rGO-CNT) papers reveal improved sp2 character and an enhancement of the specific capacitance by 75% with respect to thermally reduced GO (rGO), largely due to the effective removal of CW by oxidized CNTs. These findings disclose the relevance of the cooperative hydrogen bonding phenomena in graphene oxide paper/film electrodes for the development of improved electrochemical energy storage and sensing devices. PMID- 28989598 TI - Imaging of formaldehyde in plants with a ratiometric fluorescent probe. AB - The fluorescence monitoring of formaldehyde in real environmental samples and live plant tissues is of great importance for physiological and pathological studies. However, there is a lack of suitable chemical tools to directly trace and measure the formaldehyde activity in bio-systems, and developing effective and, in particular, selective sensors for mapping formaldehyde in live tissues still remains a great challenge. Here, we demonstrate for the first time that the ratiometric fluorescence monitoring of formaldehyde in live plant tissues is achieved with a newly developed ratiometric fluorescent probe, FAP, which effectively eliminated interference from other comparative analytes. Live tissue analyses reveal that FAP can potentially detect exogenous and endogenous formaldehyde in live Arabidopsis thaliana tissues, exposing a potential application for biological and pathological studies of formaldehyde. PMID- 28989599 TI - Photoredox ketone catalysis for the direct C-H imidation and acyloxylation of arenes. AB - The photoexcited aryl ketone-catalyzed C-H imidation of arenes and heteroarenes is reported. Using 3,6-dimethoxy-9H-thioxanthen-9-one as a catalyst in combination with a bench-stable imidating reagent, C-N bond formation proceeds with high efficiency and a broad substrate scope. A key part of this method is that the thioxanthone catalyst acts as an excited-state reductant, thus establishing an oxidative quenching cycle for radical aromatic substitution. The synthetic potential of this photoexcited ketone catalysis is further demonstrated by application to the direct C-H acyloxylation of arenes. PMID- 28989600 TI - Chemical tuning of dynamic cation off-centering in the cubic phases of hybrid tin and lead halide perovskites. AB - Hybrid halide perovskites combine ease of preparation and relatively abundant constituent elements with fascinating photophysical properties. Descriptions of the chemical and structural drivers of the remarkable properties have often focused on the potential role of the dynamic order/disorder of the molecular A site cations. We reveal here a key aspect of the inorganic framework that potentially impacts the electronic, thermal, and dielectric properties. The temperature evolution of the X-ray pair distribution functions of hybrid perovskites ABX3 [A+ = CH3NH3 (MA) or CH(NH2)2 (FA); B2+ = Sn or Pb; X- = Br, or I] in their cubic phases above 300 K reveals temperature-activated displacement (off-centering) of the divalent group 14 cations from their nominal, centered sites. This symmetry-lowering distortion phenomenon, previously dubbed emphanisis in the context of compounds such as PbTe, is attributed to Sn2+ and Pb2+ lone pair stereochemistry. Of the materials studied here, the largest displacements from the center of the octahedral sites are found in tin iodides, a more moderate effect is found in lead bromides, and the weakest effect is seen in lead iodides. The A-site cation appears to play a role as well, with the larger FA resulting in greater off-centering for both Sn2+ and Pb2+. Dynamic off-centering, which is concealed within the framework of traditional Bragg crystallography, is proposed to play a key role in the remarkable defect-tolerant nature of transport in these semiconductors via its effect on the polarizability of the lattice. The results suggest a novel chemical design principle for future materials discovery. PMID- 28989602 TI - An unprecedented amplification of near-infrared emission in a Bodipy derived pi system by stress or gelation. AB - We report an unprecedented strategy to generate and amplify near-infrared (NIR) emission in an organic chromophore by mechanical stress or gelation pathways. A greenish-yellow emitting film of pi-extended Bodipy-1, obtained from n-decane, became orange-red upon mechanical shearing, with a 15-fold enhancement in NIR emission at 738 nm. Alternatively, a DMSO gel of Bodipy-1 exhibited a 7-fold enhancement in NIR emission at 748 nm with a change in emission color from yellow to orange-red upon drying. The reason for the amplified NIR emission in both cases is established from the difference in chromophore packing, by single crystal analysis of a model compound (Bodipy-2), which also exhibited a near identical emission spectrum with red to NIR emission (742 nm). Comparison of the emission features and WAXS and FT-IR data of the sheared n-decane film and the DMSO xerogel with the single crystal data supports a head-to-tail slipped arrangement driven by the N-H...F-B bonding in the sheared or xerogel states, which facilitates strong exciton coupling and the resultant NIR emission. PMID- 28989601 TI - Multi-target-directed phenol-triazole ligands as therapeutic agents for Alzheimer's disease. AB - Alzheimer's disease (AD) is a multifactorial disease that is characterized by the formation of intracellular neurofibrillary tangles and extracellular amyloid-beta (Abeta) plaque deposits. Increased oxidative stress, metal ion dysregulation, and the formation of toxic Abeta peptide oligomers are all considered to contribute to the etiology of AD. In this work we have developed a series of ligands that are multi-target-directed in order to address several disease properties. 2-(1-(3 Hydroxypropyl)-1H-1,2,3-triazol-4-yl)phenol (POH), 2-(1-(2-morpholinoethyl)-1H 1,2,3-triazol-4-yl)phenol (PMorph), and 2-(1-(2-thiomorpholinoethyl)-1H-1,2,3 triazol-4-yl)phenol (PTMorph) have been synthesized and screened for their antioxidant capacity, Cu-binding affinity, interaction with the Abeta peptide and modulation of Abeta peptide aggregation, and the ability to limit Abeta1-42 induced neurotoxicity in human neuronal culture. The synthetic protocol and structural variance incorporated via click chemistry, highlights the influence of R-group modification on ligand-Abeta interactions and neuroprotective effects. Overall, this study demonstrates that the phenol-triazole ligand scaffold can target multiple factors associated with AD, thus warranting further therapeutic development. PMID- 28989604 TI - Macrocycle-assisted synthesis of non-stoichiometric silver(i) halide electrocatalysts for efficient chlorine evolution reaction. AB - The electrocatalytic oxidation of chloride to chlorine is a fundamental and important electrochemical reaction in industry. Herein we report the synthesis of non-stoichiometric silver halide nanoparticles through a novel macrocycle assisted bulk-to-cluster-to-nano transformation. The acquired positively charged nanoparticles expedite chloride transportation by electrostatic attraction and facilitate the formation of silver polychloride catalytic species on the surface, thus functioning as efficient and selective electrocatalysts for the chlorine evolution reaction (CER) at a very low overpotential and within a wide concentration range of chloride. The formation of uncommon non-stoichiometric nanoparticles prevents the formation of a AgCl precipitate and exposes more coordination unsaturated silver atoms to catalyze CER, finally causing a large enhancement of the atomic catalytic efficiency of silver. This study showcases a promising approach to achieve efficient catalysts from a bottom-up design. PMID- 28989603 TI - From single-site tantalum complexes to nanoparticles of Ta x N y and TaO x N y supported on silica: elucidation of synthesis chemistry by dynamic nuclear polarization surface enhanced NMR spectroscopy and X-ray absorption spectroscopy. AB - Air-stable catalysts consisting of tantalum nitride nanoparticles represented as a mixture of Ta x N y and TaO x N y with diameters in the range of 0.5 to 3 nm supported on highly dehydroxylated silica were synthesized from TaMe5 (Me = methyl) and dimeric Ta2(OMe)10 with guidance by the principles of surface organometallic chemistry (SOMC). Characterization of the supported precursors and the supported nanoparticles formed from them was carried out by IR, NMR, UV-Vis, extended X-ray absorption fine structure, and X-ray photoelectron spectroscopies complemented with XRD and high-resolution TEM, with dynamic nuclear polarization surface enhanced NMR spectroscopy being especially helpful by providing enhanced intensities of the signals of 1H, 13C, 29Si, and 15N at their natural abundances. The characterization data provide details of the synthesis chemistry, including evidence of (a) O2 insertion into Ta-CH3 species on the support and (b) a binuclear to mononuclear transformation of species formed from Ta2(OMe)10 on the support. A catalytic test reaction, cyclooctene epoxidation, was used to probe the supported nanoparticles, with 30% H2O2 serving as the oxidant. The catalysts gave selectivities up to 98% for the epoxide at conversions as high as 99% with a 3.4 wt% loading of Ta present as Ta x N y /TaO x N y . PMID- 28989605 TI - N,N-Dimethylation of nitrobenzenes with CO2 and water by electrocatalysis. AB - We have proposed a strategy for the synthesis of N,N-dimethylanilines from nitrobenzene and its derivatives, CO2, and water via an electrochemical reaction under ambient conditions. H+ generated from H2O was used as the hydrogen source. Pd/Co-N/carbon, in which the Pd nanoparticles were supported on Co-N/carbon, was designed and used as the electrocatalyst. It was found that the electrocatalyst was very efficient for the reaction in MeCN solution with 1-butyl-3 methylimidazolium bis(trifluoromethylsulfonyl)imide ([Bmim]Tf2N) as the supporting electrolyte and 1-amino-methylphosphonic acid (AMPA) as the thermal co catalyst. A series of control experiments showed that Pd/Co-N/carbon and AMPA cooperated very well in accelerating the reaction. This synthetic route has some obvious advantages, such as using CO2 and water as the reactants, ambient reaction conditions, and high yields of the desired products. This opens up a way to synthesize chemicals by the combination of an electrocatalyst and a thermal catalyst with organic compounds, CO2, and water as the reactants. PMID- 28989607 TI - Electronic delocalization, charge transfer and hypochromism in the UV absorption spectrum of polyadenine unravelled by multiscale computations and quantitative wavefunction analysis. AB - The characterization of the electronically excited states of DNA strands populated upon solar UV light absorption is essential to unveil light-induced DNA damage and repair processes. We report a comprehensive analysis of the electronic properties of the UV spectrum of single-stranded polyadenine based on theoretical calculations that include excitations over eight nucleobases of the DNA strand and environmental effects by a multiscale quantum mechanics/molecular mechanics scheme, conformational sampling by molecular dynamics, and a meaningful interpretation of the electronic structure by quantitative wavefunction analysis. We show that electronic excitations are extended mainly over two nucleobases with additional important contributions of monomer-like excitations and excitons delocalized over three monomers. Half of the spectral intensity derives from locally excited and Frenkel exciton states, while states with partial charge transfer character account for the other half and pure charge-transfer states represent only a minor contribution. The hypochromism observed when going from the isolated monomer to the strand occurs independently from delocalization and charge transfer and is instead explained by long-range environmental perturbations of the monomer states. PMID- 28989606 TI - Rapid access to substituted 2-naphthyne intermediates via the benzannulation of halogenated silylalkynes. AB - Aryne intermediates are versatile and important reactive intermediates for natural product and polymer synthesis. 2-Naphthynes are relatively unexplored because few methods provide precursors to these intermediates, especially for those bearing additional substituents. Here we report a general synthetic strategy to access 2-naphthyne precursors through an Asao-Yamamoto benzannulation of ortho-(phenylethynyl)benzaldehydes with halo-silylalkynes. This transformation provides 2-halo-3-silylnaphthalenes with complete regioselectivity. These naphthalene products undergo desilylation/dehalogenation in the presence of F- to generate the corresponding 2-naphthyne intermediate, as evidenced by furan trapping experiments. When these 2-naphthynes are generated in the presence of a copper catalyst, ortho-naphthalene oligomers, trinaphthalene, or binaphthalene products are formed selectively by varying the catalyst loading and reaction temperature. The efficiency, mild conditions, and versatility of the naphthalene products and naphthyne intermediates will provide efficient access to many new functional aromatic systems. PMID- 28989608 TI - RNA splicing process analysis for identifying antisense oligonucleotide inhibitors with padlock probe-based isothermal amplification. AB - RNA splicing, which mainly involves two transesterification steps, is a fundamental process of gene expression and its abnormal regulation contributes to serious genetic diseases. Antisense oligonucleotides (ASOs) are genetic control tools that can be used to specifically control genes through alteration of the RNA splicing pathway. Despite intensive research, how ASOs or various other factors influence the multiple processes of RNA splicing still remains obscure. This is largely due to an inability to analyze the splicing efficiency of each step in the RNA splicing process with high sensitivity. We addressed this limitation by introducing a padlock probe-based isothermal amplification assay to achieve quantification of the specific products in different splicing steps. With this amplified assay, the roles that ASOs play in RNA splicing inhibition in the first and second steps could be distinguished. We identified that 5'-ASO could block RNA splicing by inhibiting the first step, while 3'-ASO could block RNA splicing by inhibiting the second step. This method provides a versatile tool for assisting efficient ASO design and discovering new splicing modulators and therapeutic drugs. PMID- 28989609 TI - Catalyst-controlled regioselectivity in phosphine catalysis: the synthesis of spirocyclic benzofuranones via regiodivergent [3 + 2] annulations of aurones and an allenoate. AB - Catalyst-controlled regiodivergent [3 + 2] annulations of aurones and allenoates have been developed. When a dipeptide phosphine catalyst with an l-d- configuration was employed, alpha-selective [3 + 2] annulation products could be obtained with good regioselectivities and enantioselectivities. With the employment of l-l- dipeptide phosphines, gamma-selective annulation products could be selectively obtained with excellent enantioselectivities. By simply tuning the catalyst configurations, a wide range of alpha-selective or gamma selective spirocyclic benzofuranones with either aryl or alkyl substitutions could be readily prepared. DFT calculations suggest that the conformation of the dipeptide phosphines influences the hydrogen bonding interactions or the distortion energy, resulting in delicate energy differentiation in the transition states, and accounting for the observed regioselectivity. PMID- 28989610 TI - Controlled in-cell activation of RNA therapeutics using bond-cleaving bio orthogonal chemistry. AB - Temporal control of siRNA activation is a major challenge for RNAi-based therapeutics. The majority of the reported siRNA delivery systems rely on environmental factors, such as differences in extracellular and intracellular redox potential, ATP concentration, or pH to activate an siRNA payload. However dynamic endogenous environments are far too complex to rely on for controllable siRNA release and can result in premature siRNA activation prior to reaching the intended biological target. In addition, there are uncertainties about timing, degree and rate of the siRNA activation with spontaneous release approaches. Herein we describe a bio-orthogonal chemistry approach to address this important challenge. With our approach we were able achieve two major goals: complete siRNA inactivation upon immobilization of the payload on the surface of iron oxide nanoparticles and controlled in-cell activation with the addition of a small non toxic chemical trigger after sufficient cellular uptake of the nanoparticles was confirmed. We have demonstrated our in-cell activation approach using two siRNAs against green fluorescent protein (GFP) and cyclin dependent kinase 8 (CDK8) in GFP expressing MDA-MB-231 cell line. We anticipate that this methodology will potentially advance the clinical translation of RNAi-based therapeutics, as the described bio-orthogonal chemistry can be generalized for any siRNA of choice. PMID- 28989611 TI - Diversity-oriented synthesis of heterocycles and macrocycles by controlled reactions of oxetanes with alpha-iminocarbenes. AB - Using N-sulfonyl triazoles as substrates, compounds as diverse as 2-imino tetrahydrofurans, 13- and 15-membered ring aza-macrocycles can be prepared selectively via formal [1 + 4], [5 + 4 + 4] and [3 + 4 + 4 + 4] condensations of alpha-imino carbenes and oxetanes under Rh(ii)-catalysis or thermal activation. Spirocyclic N-heterocycles are also accessible by means of Buchwald-Hartwig and Pictet-Spengler cyclizations. By reaction control, substrate selection or further derivatization, a large variety of chemical structures is thus achievable. Finally, using triazoles reacting under thermal activation, interesting mechanistic insight was obtained. PMID- 28989612 TI - Inside information on xenon adsorption in porous organic cages by NMR. AB - A solid porous molecular crystal formed from an organic cage, CC3, has unprecedented performance for the separation of rare gases. Here, xenon was used as an internal reporter providing extraordinarily versatile information about the gas adsorption phenomena in the cage and window cavities of the material. 129Xe NMR measurements combined with state-of-the-art quantum chemical calculations allowed the determination of the occupancies of the cavities, binding constants, thermodynamic parameters as well as the exchange rates of Xe between the cavities. Chemical exchange saturation transfer (CEST) experiments revealed a minor window cavity site with a significantly lower exchange rate than other sites. Diffusion measurements showed significantly reduced mobility of xenon with loading. 129Xe spectra also revealed that the cage cavity sites are preferred at lower loading levels, due to more favourable binding, whereas window sites come to dominate closer to saturation because of their greater prevalence. PMID- 28989613 TI - A nickel nanocatalyst within a h-BN shell for enhanced hydrogen oxidation reactions. AB - The development of low-cost and high-performance electrocatalysts remains a challenge for the hydrogen oxidation reaction (HOR) in alkaline membrane fuel cells. Here, we have reported novel Ni@h-BN core-shell nanocatalysts consisting of nickel nanoparticles encapsulated in few-layer h-BN shells. The Ni@h-BN catalysts exhibit an improved HOR performance compared with the bare Ni nanoparticles. In situ characterization experiments and density functional theory calculations indicate that the interactions of the O, H, and OH species with the Ni surface under the h-BN shell are weakened, which helps to maintain the active metallic Ni phase both in air and in the electrolyte and strengthen the HOR processes occurring at the h-BN/Ni interfaces. These results suggest a new route for designing high-performance non-noble metal electrocatalysts with encapsulating two-dimensional material overlayers for HOR reactions. PMID- 28989614 TI - Universal sensor array for highly selective system identification using two dimensional nanoparticles. AB - A typical lock-and-key sensing strategy, relying only on the most dominant interactions between the probe and target, could be too limiting. In reality, the information received upon sensing is much richer. Non-specific events due to various intermolecular forces contribute to the overall received information with different degrees, and when analyzed, could provide a much more powerful detection opportunity. Here, we have assembled a highly selective universal sensor array using water-soluble two-dimensional nanoparticles (nGO, MoS2 and WS2) and fluorescent DNA molecules. The array is composed of 12 fluorescently silent non-specific nanoreceptors (2D-nps) and used for the identification of three radically different systems; five proteins, three types of live breast cancer cells and a structure-switching event of a macromolecule. The data matrices for each system were processed using Partial Least Squares (PLS) discriminant analysis. In all of the systems, the sensor array was able to identify each object or event as separate clusters with 95% confidence and without any overlap. Out of 15 unknown entities with unknown protein concentrations tested, 14 of them were predicted successfully with correct concentration. 8 breast cancer cell samples out of 9 unknown entities from three cell types were predicted correctly. During the assembly of each nanoprobe, the intrinsic non-covalent interactions between unmodified 2D nanoparticles and ssDNAs were exploited. The unmodified 2D materials offer remarkable simplicity in the layout and the use of ssDNAs as probes provides limitless possibilities because the natural interaction of a ssDNA and 2D surface can be fine-tuned with the nucleobase composition, oligonucleotide length and type of 2D nanomaterial. Therefore, the approach described here can be advanced and fine-tuned indefinitely for meeting a particular sensing criterion. Though we have only studied three distinct elements, this approach is universal enough to be applied to a wide-range of systems. PMID- 28989615 TI - Enantioselective catalytic beta-amination through proton-coupled electron transfer followed by stereocontrolled radical-radical coupling. AB - A new mechanistic approach for the catalytic, enantioselective conjugate addition of nitrogen-based nucleophiles to acceptor-substituted alkenes is reported, which is based on a visible light induced and phosphate base promoted transfer of a single electron from a nitrogen nucleophile to a catalyst-bound acceptor substituted alkene, followed by a stereocontrolled C-N bond formation through stereocontrolled radical-radical coupling. Specifically, N-aryl carbamates are added to the beta-position of alpha,beta-unsaturated 2-acyl imidazoles using a visible light activated photoredox mediator in combination with a chiral-at rhodium Lewis acid catalyst and a weak phosphate base, affording new C-N bonds in a highly enantioselective fashion with enantioselectivities reaching up to 99% ee and >99 : 1 dr for a menthol-derived carbamate. As an application, the straightforward synthesis of a chiral beta-amino acid ester derivative is demonstrated. PMID- 28989616 TI - Synthesis and evaluation of MR probes for targeted-reporter imaging. AB - Visualizing disease heterogeneity remains a challenging task since most imaging agents are targeted to a single receptor. We describe the development of an MR platform able to report on multiple molecular events. Enzyme activation and enhanced cellular uptake of this modular probe make it suitable for subsequent targeted-reporter imaging applications. PMID- 28989617 TI - Stimuli-responsive nucleic acid-functionalized metal-organic framework nanoparticles using pH- and metal-ion-dependent DNAzymes as locks. AB - A versatile approach to modify metal-organic framework nanoparticles (NMOFs) with nucleic acid tethers, using the "click chemistry" method is introduced. The nucleic acid-functionalized NMOFs are used to prepare stimuli-responsive carriers of loads (fluorescence probes or anti-cancer drugs). Two different stimuli responsive nucleic acid-based NMOFs are presented. One system involves the preparation of pH-responsive NMOFs. The NMOFs are loaded with fluorophores or doxorubicin anti-cancer drug and locked in the NMOFs by pH-responsive DNA duplex capping units. At pH = 5.0 the capping units are unlocked, leading to the release of the loads. The AS1411 aptamer is conjugated to the locking units as the targeting unit for the nucleolin biomarker present in cancer cells. The pH responsive doxorubicin-loaded NMOFs and, in particular, the AS1411 aptamer modified pH-responsive NMOFs reveal selective, targeted, cytotoxicity toward MDA MB-231 breast cancer cells. A second system involves the synthesis of NMOFs that are loaded with fluorophores or doxorubicin and capped with metal-ion-dependent DNAzyme/substrate complexes as locking units (metal ion = Mg2+ or Pb2+ ions). In the presence of the respective metal ions, the nucleic acid locking units are cleaved off, resulting in the release of the loads. Also, "smart" Mg2+-ion dependent DNAzyme capped doxorubicin-loaded NMOFs are synthesized via the integration of the ATP aptamer sequence in the loop domain of the Mg2+-dependent DNAzyme. The unlocking of these NMOFs proceeds effectively only in the presence of ATP and Mg2+ ions, acting as cooperative triggers. As ATP is over-expressed in cancer cells, the "smart" carrier provides sense-and-treat functions. The "smart" ATP/Mg2+-triggered doxorubicin-loaded NMOFs reveal selective cytotoxicity toward MDA-MB-231 cancer cells. Beyond the use of the metal-ion-dependent DNAzymes as ion-responsive locks of drug-loaded NMOF carriers, the DNAzyme-capped fluorophore loaded NMOFs are successfully applied as functional units for multiplexed ion sensing and for the design of logic-gate systems. PMID- 28989618 TI - Learning reduced kinetic Monte Carlo models of complex chemistry from molecular dynamics. AB - We propose a novel statistical learning framework for automatically and efficiently building reduced kinetic Monte Carlo (KMC) models of large-scale elementary reaction networks from data generated by a single or few molecular dynamics simulations (MD). Existing approaches for identifying species and reactions from molecular dynamics typically use bond length and duration criteria, where bond duration is a fixed parameter motivated by an understanding of bond vibrational frequencies. In contrast, we show that for highly reactive systems, bond duration should be a model parameter that is chosen to maximize the predictive power of the resulting statistical model. We demonstrate our method on a high temperature, high pressure system of reacting liquid methane, and show that the learned KMC model is able to extrapolate more than an order of magnitude in time for key molecules. Additionally, our KMC model of elementary reactions enables us to isolate the most important set of reactions governing the behavior of key molecules found in the MD simulation. We develop a new data-driven algorithm to reduce the chemical reaction network which can be solved either as an integer program or efficiently using L1 regularization, and compare our results with simple count-based reduction. For our liquid methane system, we discover that rare reactions do not play a significant role in the system, and find that less than 7% of the approximately 2000 reactions observed from molecular dynamics are necessary to reproduce the molecular concentration over time of methane. The framework described in this work paves the way towards a genomic approach to studying complex chemical systems, where expensive MD simulation data can be reused to contribute to an increasingly large and accurate genome of elementary reactions and rates. PMID- 28989619 TI - Efficient photocatalytic carbon monoxide production from ammonia and carbon dioxide by the aid of artificial photosynthesis. AB - Ammonium bicarbonate (NH4HCO3) was generated by the absorption of carbon dioxide (CO2) into an aqueous solution of ammonia (NH3). NH4HCO3 was successfully used to achieve highly efficient photocatalytic conversion of CO2 to carbon monoxide (CO). NH3 and/or ammonium ions (NH4+) derived from NH4HCO3 in aqueous solution were decomposed into nitrogen (N2) and hydrogen (H2). Stoichiometric amounts of the N2 oxidation product and the CO and H2 reduction products were generated when the photocatalytic reaction was carried out in aqueous NH4HCO3 solution. NH3 and/or NH4+ functioned as electron donors in the photocatalytic conversion of CO2 to CO. A CO formation rate of 0.5 mmol h-1 was obtained using 500 mg of catalyst (approximately 7500 ppm) in ambient conditions (303 K, 101.3 kPa). Our results demonstrated that NH4HCO3 is a novel inorganic sacrificial reagent, which can be used to increase the efficiency of photocatalytic CO production to achieve one step CO2 capture, storage and conversion. PMID- 28989620 TI - Controlling the excited-state dynamics of low band gap, near-infrared absorbers via proquinoidal unit electronic structural modulation. AB - While the influence of proquinoidal character upon the linear absorption spectrum of low optical bandgap pi-conjugated polymers and molecules is well understood, its impact upon excited-state relaxation pathways and dynamics remains obscure. We report the syntheses, electronic structural properties, and excited-state dynamics of a series of model highly conjugated near-infrared (NIR)-absorbing chromophores based on a (porphinato)metal(ii)-proquinoidal spacer (porphinato)metal(ii) (PM-Sp-PM) structural motif. A combination of excited-state dynamical studies and time-dependent density functional theory calculations: (i) points to the cardinal role that excited-state configuration interaction (CI) plays in determining the magnitudes of S1 -> S0 radiative (kr), S1 -> T1 intersystem crossing (kISC), and S1 -> S0 internal conversion (kIC) rate constants in these PM-Sp-PM chromophores, and (ii) suggests that a primary determinant of CI magnitude derives from the energetic alignment of the PM and Sp fragment LUMOs (DeltaEL). These insights not only enable steering of excited state relaxation dynamics of high oscillator strength NIR absorbers to realize either substantial fluorescence or long-lived triplets (tauT1 > MUs) generated at unit quantum yield (PhiISC = 100%), but also crafting of those having counter intuitive properties: for example, while (porphinato)platinum compounds are well known to generate non-emissive triplet states (PhiISC = 100%) upon optical excitation at ambient temperature, diminishing the extent of excited-state CI in these systems realizes long-wavelength absorbing heavy-metal fluorophores. This work highlights approaches to: (i) modulate low-lying singlet excited-state lifetime over the picosecond-to-nanosecond time domain, (ii) achieve NIR fluorescence with quantum yields up to 25%, (iii) tune the magnitude of S1-T1 ISC rate constant from 109 to 1012 s-1 and (iv) realize T1-state lifetimes that range from ~0.1 to several MUs, for these model PM-Sp-PM chromophores, and renders new insights to evolve bespoke photophysical properties for low optical bandgap pi conjugated polymers and molecules based on proquinoidal conjugation motifs. PMID- 28989621 TI - Utilizing light-triggered plasmon-driven catalysis reactions as a template for molecular delivery and release. AB - Due to the facile manipulation and non-invasive nature of light-triggered release, it is one of the most potent ways to selectively and remotely deliver a molecular target. Among the various carrier platforms, plasmonic nanoparticles possess advantages such as enhanced cellular uptake and easy loading of "cargo" molecules. Two general strategies are currently utilized to achieve light-induced molecule release from plasmonic nanoparticles. The first uses femtosecond laser pulses to directly break the bond between the nanoparticle and the loaded target. The other requires significant photo-thermal effects to weaken the interaction between the cargo molecules and nanoparticle-attached host molecules. Different from above mechanisms, herein, we introduce a new light-controlled molecular release method by taking advantage of a plasmon-driven catalytic reaction at the particle surface. In this strategy, we link the target to a plasmon responsive molecule, 4-aminobenzenethiol (4-ABT), through the robust and simple EDC coupling reaction and subsequently load the complex onto the particles via the strong Au thiol interaction. Upon continuous-wave (CW) laser illumination, the excited surface plasmon catalyzes the formation of 4,4'-dimercaptoazobenzenethiol (DMAB) and simultaneously releases the loaded molecules with high efficiency. This method does not require the use of high-power pulsed lasers, nor does it rely on photo-thermal effects. We believe that plasmon-driven release strategies open a new direction for the designing of next-generation light-triggered release processes. PMID- 28989622 TI - Using highly emissive and environmentally sensitive o-carborane-functionalized metallophosphors to monitor mitochondrial polarity. AB - Mitochondria as vital intracellular organelles play critical roles in multiple physiological processes, and their polarity is a crucial characteristic that can reveal the intracellular environment and impact cellular events. In this work, we designed and synthesized a novel series of highly emissive and environmentally sensitive phosphorescent iridium(iii) complexes (2a-2e, 3a-3e and 4) functionalized by o-carborane. These complexes showed high emission quantum yields both in solution and in solid state (up to PhiPL = 0.82), long emission lifetime and tunable emission wavelength over 74 nm by introduction of a carboranyl motif in their ligands. Importantly, all the complexes have shown significant solvatochromic effects in contrast to the carborane-free control complex. Among them, complex 2d shows the highest sensitivity to polarity of solvents with a MPPS (maximum peak phosphorescence shift) value of 42 nm and clear dependence of phosphorescence lifetime on solvent polarity. Interestingly, complex 2d can easily penetrate into cells and preferentially distribute in mitochondria. To utilize these properties, the first phosphorescent imaging of mitochondrial polarity has been realized by photoluminescence lifetime imaging microscopy (PLIM), which can monitor mitochondria-relevant cellular processes such as cell apoptosis and distinguish cancer cells from normal cells. Compared to intensity-based sensing, lifetime-based detection is independent of the probe concentration, excitation power and photobleaching of probes, which can show high accuracy and reproducibility. PMID- 28989623 TI - ENDOR characterization of an iron-alkene complex provides insight into a corresponding organometallic intermediate of nitrogenase. AB - A bio-organometallic intermediate, denoted PA, was previously trapped during the reduction of propargyl alcohol to allyl alcohol (AA) by nitrogenase, and a similar one was trapped during acetylene reduction, representing foundational examples of alkene binding to a metal center in biology. ENDOR spectroscopy led to the conclusion that these intermediates have eta2 binding of the alkene, with the hydrogens on the terminal carbon structurally/magnetically equivalent and related by local mirror symmetry. However, our understanding of both the PA intermediate, and of the dependability of the ENDOR analysis on which this understanding was based, was constrained by the absence of reference iron-alkene complexes for EPR/ENDOR comparison. Here, we report an ENDOR study of the crystallographically characterized biomimetic iron(i) complex 1, which exhibits eta2 coordination of styrene, thus connecting hyperfine and structural parameters of an Fe-bound alkene fragment for the first time. A tilt of the alkene plane of 1 from normal to the crystallographic Fe-C2-C1 plane causes substantial differences in the dipolar couplings of the two terminal vinylic protons. Comparison of the hyperfine couplings of 1 and PA confirms the proposed symmetry of PA, and that the eta2 interaction forms a scalene Fe-C-C triangle, rather than an isosceles triangle. This spectroscopic study of a structurally characterized complex thus shows the exceptional sensitivity of ENDOR spectroscopy to structural details, while enhancing our understanding of the geometry of a key nitrogenase adduct. PMID- 28989624 TI - Formation and decay of negative ion states up to 11 eV above the ionization energy of the nanofabrication precursor HFeCo3(CO)12. AB - In single electron collisions with the heteronuclear metal carbonyl compound HFeCo3(CO)12 we observe the formation of long-lived negative ion states up to about 20 eV, 11 eV above its ionization energy. These transient negative ions (TNIs) relax through dissociation (dissociative electron attachment, DEA), losing up to all 12 CO ligands, demonstrating their resilience towards reemission of the captured electron - even at such very high energies. This is unique in DEA and we hypothesize that this phenomenon is rooted in the orbital structure enabling a scaffold of multi-particle, electronically excited resonances. We support this with calculated MO-diagrams revealing dense bands of energy levels near the HOMO LUMO gap. HFeCo3(CO)12 is a promising focused electron beam induced deposition (FEBID) precursor and we argue that its unusual DEA behavior relates to its exceptional performance in FEBID. This may be general to a class of molecules with high potential for nano-fabrication by FEBID. PMID- 28989625 TI - Enhancing the reactivity of nickel(ii) in hydrogen evolution reactions (HERs) by beta-hydrogenation of porphyrinoid ligands. AB - Fine-tuning of the porphyrin beta-periphery is important for naturally occurring metal tetrapyrroles to exert diverse biological roles. Here we describe how this approach is also applied to design molecular catalysts, as exemplified by Ni(ii) porphyrinoids catalyzing the hydrogen evolution reaction (HER). We found that beta-hydrogenation of porphyrin remarkably enhances the electrocatalytic HER reactivity (turnover frequencies of 6287 vs. 265 s-1 for Ni(ii) chlorin (Ni-2) and porphyrin (Ni-1), and of 1737 vs. 342 s-1 for Ni(ii) hydroporpholactone (Ni 4) and porpholactone (Ni-3), respectively) using trifluoroacetic acid (TFA) as the proton source. DFT calculations suggested that after two-electron reduction, beta-hydrogenation renders more electron density located on the Ni center and thus prefers to generate a highly reactive nickel hydride intermediate. To demonstrate this, decamethylcobaltocene Co(Cp*)2 was used as a chemical reductant. [Ni-2]2- reacts ca. 30 times faster than [Ni-1]2- with TFA, which is in line with the electrocatalysis and computational results. Thus, such subtle structural changes inducing the distinctive reactivity of Ni(ii) not only test the fundamental understanding of natural Ni tetrapyrroles but also provide a valuable clue to design metal porphyrinoid catalysts. PMID- 28989626 TI - Borylation of fluorinated arenes using the boron-centred nucleophile B(CN)32- - a unique entry to aryltricyanoborates. AB - The potassium salt of the boron-centred nucleophile B(CN)32- (1) readily reacts with perfluorinated arenes, such as hexafluorobenzene, decafluorobiphenyl, octafluoronaphthalene and pentafluoropyridine, which results in KF and the K+ salts of the respective borate anions with one {B(CN)3} unit bonded to the (hetero)arene. An excess of K21 leads to the successive reaction of two or, in the case of perfluoropyridine, even three C-F moieties and the formation of di- and trianions, respectively. Moreover, all of the 11 partially fluorinated benzene derivatives, C6F6-n H n (n = 1-5), generally react with K21 to give new tricyano(phenyl)borate anions with high chemo- and regioselectivity. A decreasing number of fluorine substituents on benzene results in a decrease in the reaction rate. In the cases of partially fluorinated benzenes, the addition of LiCl is advantageous or even necessary to facilitate the reaction. Also, pentafluorobenzenes R-C6F5 (R = -CN, -OMe, -Me, or -CF3) react via C-F/C-B exchange that mostly occurs in the para position and to a lesser extent in the meta or ortho positions. Most of the reactions proceed via an SNAr mechanism. The reaction of 1,4-F2C6H4 with K21 shows that an aryne mechanism has to be considered in some cases as well. In summary, a wealth of new stable tricyano(aryl)borates have been synthesised and fully characterized using multi NMR spectroscopy and most of them were characterised using single-crystal X-ray diffraction. PMID- 28989627 TI - X-ray circular dichroism signals: a unique probe of local molecular chirality. AB - Core-resonant circular dichroism (CD) signals are induced by molecular chirality and vanish for achiral molecules and racemic mixtures. The highly localized nature of core excitations makes them ideal probes of local chirality within molecules. Simulations of the circular dichroism spectra of several molecular families illustrate how these signals vary with the electronic coupling to substitution groups, the distance between the X-ray chromophore and the chiral center, geometry, and chemical structure. Clear insight into the molecular structure is obtained through analysis of the X-ray CD spectra. PMID- 28989628 TI - Two-step model for ultrafast interfacial electron transfer: limitations of Fermi's golden rule revealed by quantum dynamics simulations. AB - Interfacial electron transfer (IET) is one of the crucial steps in the light harvesting process that occurs in various assemblies for solar energy conversion, such as dye-sensitized solar cells or dye-sensitized photoelectrosynthesis cells. Computational studies of IET in dye-semiconductor assemblies employ a variety of approaches, ranging from phenomenological models such as Fermi's golden rule to more complex methods relying on explicit solutions of the time-dependent Schrodinger equation. This work investigates IET in a model pyridine-TiO2 assembly, with the goals of assessing the validity of Fermi's golden rule for calculation of the IET rates, understanding the importance of conformational sampling in modeling the IET process, and establishing an approach to rapid computational screening of dye-sensitizers that undergo fast IET into the semiconductor. Our results suggest that IET is a two-step process, in which the electron is first transferred into the semiconductor surface states, followed by diffusion of the electron into the nanoparticle bulk states. Furthermore, while Fermi's golden rule and related approaches are appropriate for predicting the initial IET rate (i.e., the initial transfer of an electron from the dye into the semiconductor surface states), they are not reliable for prediction of the overall IET rate. The inclusion of conformational sampling at room temperature into the model offers a more complete picture of the IET process, leading to a distribution of IET rates with a median rate faster than the IET rate obtained for the fully-optimized structure at 0 K. Finally, the two most important criteria for determination of the initial IET rate are the percentage of electron density on the linker in the excited state as well as the number of semiconductor acceptor states available at the energy of the excited state. Both of these can be obtained from relatively simple electronic structure calculations at either ab initio or semiempirical levels of theory and can thus be used for rapid screening of dyes with the desired properties. PMID- 28989629 TI - Halogenation of glycopeptide antibiotics occurs at the amino acid level during non-ribosomal peptide synthesis. AB - Halogenation plays a significant role in the activity of the glycopeptide antibiotics (GPAs), although up until now the timing and therefore exact substrate involved was unclear. Here, we present results combined from in vivo and in vitro studies that reveal the substrates for the halogenase enzymes from GPA biosynthesis as amino acid residues bound to peptidyl carrier protein (PCP) domains from the non-ribosomal peptide synthetase machinery: no activity was detected upon either free amino acids or PCP-bound peptides. Furthermore, we show that the selectivity of GPA halogenase enzymes depends upon both the structure of the bound amino acid and the PCP domain, rather than being driven solely via the PCP domain. These studies provide the first detailed understanding of how halogenation is performed during GPA biosynthesis and highlight the importance and versatility of trans-acting enzymes that operate during peptide assembly by non-ribosomal peptide synthetases. PMID- 28989630 TI - Efficient stabilisation of a dihydrogenphosphate tetramer and a dihydrogenpyrophosphate dimer by a cyclic pseudopeptide containing 1,4 disubstituted 1,2,3-triazole moieties. AB - A cyclic pseudooctapeptide 2 is described containing 1,4-disubstituted 1,2,3 triazole moieties. This compound features eight converging hydrogen bond donors along the ring, namely four amide NH and four triazole CH groups, which enable 2 to engage in interactions with anions. While fully deprotonated sulfate anions exhibit only moderate affinity for 2, protonated anions such as dihydrogenpyrophosphate and dihydrogenphosphate anions are strongly bound. Complexation of the phosphate-derived anions involves sandwiching of a dihydrogenpyrophosphate dimer or a dihydrogenphosphate tetramer between two pseudopeptide rings. X-ray crystallography provided structural information, while 1H NMR spectroscopy, mass spectrometry, and isothermal titration calorimetry demonstrated that these complexes are stable in solution (2.5 vol% water/DMSO) and can even be transferred without decomposition into the gas phase. The observed high thermodynamic stabilities are attributed to the mutual reinforcement of the interactions between the individual complex components, namely, hydrogen-bonding between the anions, multiple hydrogen bonding interactions between the anion aggregates and the triazole CH and NH hydrogen bond donors of 2, and potential dispersive interactions between the closely arranged pseudopeptide rings. Pseudopeptide 2 thus represents a promising lead for the construction of phosphate receptors, whose binding selectivity makes use of the unique ability of certain anions to assemble into higher aggregates. PMID- 28989631 TI - Solid-state molecular organometallic chemistry. Single-crystal to single-crystal reactivity and catalysis with light hydrocarbon substrates. AB - Single-crystal to single-crystal solid/gas reactivity and catalysis starting from the precursor sigma-alkane complex [Rh(Cy2PCH2CH2PCy2)(eta2eta2-NBA)][BArF4] (NBA = norbornane; ArF = 3,5-(CF3)2C6H3) is reported. By adding ethene, propene and 1 butene to this precursor in solid/gas reactions the resulting alkene complexes [Rh(Cy2PCH2CH2PCy2)(alkene) x ][BArF4] are formed. The ethene (x = 2) complex, [Rh(Cy2PCH2CH2PCy2)(ethene)2][BArF4]-Oct, has been characterized in the solid state (single-crystal X-ray diffraction) and by solution and solid-state NMR spectroscopy. Rapid, low temperature recrystallization using solution methods results in a different crystalline modification, [Rh(Cy2PCH2CH2PCy2)(ethene)2][BArF4]-Hex, that has a hexagonal microporous structure (P6322). The propene complex (x = 1) [Rh(Cy2PCH2CH2PCy2)(propene)][BArF4] is characterized as having a pi-bound alkene with a supporting gamma-agostic Rh...H3C interaction at low temperature by single crystal X-ray diffraction, variable temperature solution and solid-state NMR spectroscopy, as well as periodic density functional theory (DFT) calculations. A fluxional process occurs in both the solid-state and solution that is proposed to proceed via a tautomeric allyl-hydride. Gas/solid catalytic isomerization of d3 propene, H2C 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 1111111111111111111111111111111111 1111111111111111111111111111111111 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 1111111111111111111111111111111111 1111111111111111111111111111111111 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 CHCD3, using [Rh(Cy2PCH2CH2PCy2)(eta2eta2 NBA)][BArF4] scrambles the D-label into all possible positions of the propene, as shown by isotopic perturbation of equilibrium measurements for the agostic interaction. Periodic DFT calculations show a low barrier to H/D exchange (10.9 kcal mol-1, PBE-D3 level), and GIPAW chemical shift calculations guide the assignment of the experimental data. When synthesized using solution routes a bis propene complex, [Rh(Cy2PCH2CH2PCy2)(propene)2][BArF4], is formed. [Rh(Cy2PCH2CH2PCy2)(butene)][BArF4] (x = 1) is characterized as having 2-butene bound as the cis-isomer and a single Rh...H3C agostic interaction. In the solid state two low-energy fluxional processes are proposed. The first is a simple libration of the 2-butene that exchanges the agostic interaction, and the second is a butene isomerization process that proceeds via an allyl-hydride intermediate with a low computed barrier of 14.5 kcal mol-1. [Rh(Cy2PCH2CH2PCy2)(eta2eta2 NBA)][BArF4] and the polymorphs of [Rh(Cy2PCH2CH2PCy2)(ethene)2][BArF4] are shown to be effective in solid-state molecular organometallic catalysis (SMOM-Cat) for the isomerization of 1-butene to a mixture of cis- and trans-2-butene at 298 K and 1 atm, and studies suggest that catalysis is likely dominated by surface active species. [Rh(Cy2PCH2CH2PCy2)(eta2eta2-NBA)][BArF4] is also shown to catalyze the transfer dehydrogenation of butane to 2-butene at 298 K using ethene as the sacrificial acceptor. PMID- 28989632 TI - Temporal switching of an amphiphilic self-assembly by a chemical fuel-driven conformational response. AB - The spatial and temporal control of self-assemblies is the latest scientific hurdle in supramolecular chemistry which is inspired by the functioning of biological systems fueled by chemical signals. In this study, we work towards alleviating this scenario by employing a unique amphiphilic foldamer that operates under the effect of a chemical fuel. The conformational changes in the foldamer amplify into observable morphological changes in its amphiphilic assembly that are controlled by external molecular cues (fuel). We take advantage of this redox responsive foldamer to affect its conformation in a temporal manner by an enzymatic pathway. The temporal characteristics of the transient conformation/assembly can be modulated by varying the concentrations of the fuel and enzyme. We believe that such a design strategy can have positive consequences in designing molecular and supramolecular systems for future active, adaptive and autonomous materials. PMID- 28989633 TI - Mechanical measurement of hydrogen bonded host-guest systems under non equilibrium, near-physiological conditions. AB - Decades after the birth of supramolecular chemistry, there are many techniques to measure noncovalent interactions, such as hydrogen bonding, under equilibrium conditions. As ensembles of molecules rapidly lose coherence, we cannot extrapolate bulk data to single-molecule events under non-equilibrium conditions, more relevant to the dynamics of biological systems. We present a new method that exploits the high force resolution of optical tweezers to measure at the single molecule level the mechanical strength of a hydrogen bonded host-guest pair out of equilibrium and under near-physiological conditions. We utilize a DNA reporter to unambiguously isolate single binding events. The Hamilton receptor-cyanuric acid host-guest system is used as a test bed. The force required to dissociate the host-guest system is ~17 pN and increases with the pulling rate as expected for a system under non-equilibrium conditions. Blocking one of the hydrogen bonding sites results in a significant decrease of the force-to-break by 1-2 pN, pointing out the ability of the method to resolve subtle changes in the mechanical strength of the binding due to the individual H-bonding components. We believe the method will prove to be a versatile tool to address important questions in supramolecular chemistry. PMID- 28989634 TI - Near-infrared luminescent metallacrowns for combined in vitro cell fixation and counter staining. AB - Cell fixation is an essential approach for preserving cell morphology, allowing the targeting and labelling of biomolecules with fluorescent probes. One of the key requirements for more efficient fluorescent labelling is the preservation of cell morphology, which usually requires a combination of several fixation techniques. In addition, the use of a counter stain is often essential to improve the contrast of the fluorescent probes. Current agents possess significant limitations, such as low resistance toward photobleaching and sensitivity to changes in the microenvironment. Luminescent Ln3+ 'encapsulated sandwich' metallacrowns (MCs) overcome these drawbacks and offer complementary advantages. In particular, they emit sharp emission bands, possess a large difference between excitation and emission wavelengths and do not photobleach. Herein, MCs formed with pyrazinehydroxamic acid (Ln3+[Zn(ii)MCpyzHA], Ln3+ = Yb, Nd) were used, combined with near-infrared (NIR) counter staining and fixation agents for HeLa cells upon an initial five minute exposure to UV-A light. The validity and quality of the cell fixation were assessed with Raman spectroscopy. Analysis of the NIR luminescence properties of these MCs was performed under different experimental conditions, including in a suspension of stained cells. Moreover, the high emission intensity of Ln3+[Zn(ii)MCpyzHA] in the NIR region allows these MCs to be used for imaging with standard CCD cameras installed on routine fluorescence microscopes. Finally, the NIR-emitting Ln3+[Zn(ii)MCpyzHA] compounds combine, within a single molecule, features such as cell fixation and staining abilities, good photostability and minimal sensitivity of the emission bands to the local microenvironment, and they are highly promising for establishing the next generation of imaging agents with a single biodistribution. PMID- 28989635 TI - Intra-molecular origin of the spin-phonon coupling in slow-relaxing molecular magnets. AB - We perform a systematic investigation of the spin-phonon coupling leading to spin relaxation in the prototypical mononuclear single molecule magnet [(tpaPh)Fe]-. In particular we analyze in detail the nature of the most relevant vibrational modes giving rise to the relaxation. Our fully ab initio calculations, where the phonon modes are evaluated at the level of density functional theory and the spin phonon coupling by mapping post-Hartree-Fock electronic structures onto an effective spin Hamiltonian, reveal that acoustic phonons are not active in the spin-phonon relaxation process of dilute SMMs crystals. Furthermore, we find that intra-molecular vibrational modes produce anisotropy tensor modulations orders of magnitude higher than those associated to rotations. In light of these results we are able to suggest new designing rules for spin-long-living SMMs which go beyond the tailoring of static molecular features but fully take into account dynamical features of the vibrational thermal bath evidencing those internal molecular distortions more relevant to the spin dynamics. PMID- 28989636 TI - Bright persistent luminescence from pure organic molecules through a moderate intermolecular heavy atom effect. AB - Generally, strong phosphorescence always implies a short luminescence lifetime. So, pure organic molecules with strong persistent phosphorescence at room temperature are rarely explored. Here, a new strategy is used to explore strong persistent phosphorescence of carbazole derivatives through an intermolecular moderate heavy atom effect. Flexible alkyl chains were inserted between the heavy atom and carbazole moieties so as to avoid a strong internal heavy atom affect. The results indicate that the photoluminescence properties of crystals strongly depend on molecular stacking in crystal states. Moreover, seven molecules among eight carbazole derivatives exhibit persistent room-temperature phosphorescence in their crystals and the PhiP values of three compounds exceed 9.5%. Notably, when a 6-(4-bromophenoxy)hexyl group is linked to carbazole, the ambient phosphorescent quantum yield reaches 39.5% and the lifetime is as long as 200 ms. Moreover, it emitted white light with a luminescent efficiency of 72.6% owing to the coexistence of strong fluorescence and phosphorescence. PMID- 28989637 TI - Selective C-O bond formation via a photocatalytic radical coupling strategy: access to perfluoroalkoxylated (ORF) arenes and heteroarenes. AB - Development of an efficient process that employs commercially available and cost effective reagents for the synthesis of perfluoroalkoxylated aromatic compounds (Ar-ORF) remains a daunting challenge in organic synthesis. Herein, we report the first catalytic protocol using readily available perfluoroalkyl iodides (RFI) and N-(hetero)aryl-N-hydroxylamides to access a wide range of perfluoroalkoxylated (hetero)arenes. Mild reaction conditions allow for selective O-RF bond formation over a broad substrate scope and are tolerant of a wide variety of functional groups. Mechanistic studies suggest the formation and recombination of persistent N-hydroxyl radicals and transient RF radicals under photocatalytic reaction conditions to generate N-ORF compounds that rearrange to afford the desired products. PMID- 28989639 TI - Synthesis of 'reactive' and covalent polymeric multilayer coatings with durable superoleophobic and superoleophilic properties under water. AB - Bioinspired underwater super-oil-wettability (superoleophilic/superoleophobic) properties are emerging as a potential avenue for developing smart materials for addressing issues related to healthcare, environment, energy, etc. However, the inherent poor durability of the materials that are mostly developed using polymeric hydrogel, metal oxide coatings and electrostatic multilayers often challenges the application of these wettability properties in practical scenarios. Here, 'amine-reactive' polymeric multilayers of nano-complex were developed to fabricate 'internal' underwater superoleophobic/superoleophilic coatings with impeccable physical/chemical durability. This allows the super wetting properties to exist beyond the surface of the material and remain intact even after severe physical damage including erosion of the material and continuous exposure to an artificial-marine environment for more than 80 days. Moreover, this current design allowed for independent revalidation of some key hypotheses with direct experimental demonstrations, and provided a basis to develop highly durable super-oil-wettability properties under water. It is believed that this contemporary study will make a worthwhile contribution on developing multifunctional materials for widespread practical applications by exploiting these super-oil-wetting properties. PMID- 28989638 TI - Evaluating the electronic structure of formal LnII ions in LnII(C5H4SiMe3)31- using XANES spectroscopy and DFT calculations. AB - The isolation of [K(2.2.2-cryptand)][Ln(C5H4SiMe3)3], formally containing LnII, for all lanthanides (excluding Pm) was surprising given that +2 oxidation states are typically regarded as inaccessible for most 4f-elements. Herein, X-ray absorption near-edge spectroscopy (XANES), ground-state density functional theory (DFT), and transition dipole moment calculations are used to investigate the possibility that Ln(C5H4SiMe3)31- (Ln = Pr, Nd, Sm, Gd, Tb, Dy, Y, Ho, Er, Tm, Yb and Lu) compounds represented molecular LnII complexes. Results from the ground state DFT calculations were supported by additional calculations that utilized complete-active-space multi-configuration approach with second-order perturbation theoretical correction (CASPT2). Through comparisons with standards, Ln(C5H4SiMe3)31- (Ln = Sm, Tm, Yb, Lu, Y) are determined to contain 4f6 5d0 (SmII), 4f13 5d0 (TmII), 4f14 5d0 (YbII), 4f14 5d1 (LuII), and 4d1 (YII) electronic configurations. Additionally, our results suggest that Ln(C5H4SiMe3)31 (Ln = Pr, Nd, Gd, Tb, Dy, Ho, and Er) also contain LnII ions, but with 4f n 5d1 configurations (not 4f n+1 5d0). In these 4f n 5d1 complexes, the C3h-symmetric ligand environment provides a highly shielded 5d-orbital of a' symmetry that made the 4f n 5d1 electronic configurations lower in energy than the more typical 4f n+1 5d0 configuration. PMID- 28989640 TI - CoO x nanoparticle anchored on sulfonated-graphite as efficient water oxidation catalyst. AB - Development of efficient, robust and earth-abundant water oxidation catalysts (WOCs) is extremely desirable for water splitting by electrolysis or photocatalysis. Herein, we report cobalt oxide nanoparticles anchored on the surface of sulfonated graphite (denoted as "CoO x @G-Ph-SN") to exhibit unexpectedly efficient water oxidation activity with a turnover frequency (TOF) of 1.2 s-1; two or three orders of magnitude higher than most cobalt-based oxide WOCs reported so far. The CoO x @G-Ph-SN nanocomposite can be easily prepared by a soft hydrothermal route to have an average CoO x size below 2 nm. Additionally, the loading of CoO x @G-Ph-SN catalyst on the surface of a BiVO4 or Fe2O3 photoanode can boost remarkably the photoanode currents for robust photocatalytic water oxidation under visible light irradiation. Its excellent activity and photochemical stability for water oxidation suggest that this ultrasmall cobalt based composite is a promising candidate for solar fuel production. PMID- 28989641 TI - On the incompatibility of lithium-O2 battery technology with CO2. AB - When solubilized in a hexacarboxamide cryptand anion receptor, the peroxide dianion reacts rapidly with CO2 in polar aprotic organic media to produce hydroperoxycarbonate (HOOCO2-) and peroxydicarbonate (-O2COOCO2-). Peroxydicarbonate is subject to thermal fragmentation into two equivalents of the highly reactive carbonate radical anion, which promotes hydrogen atom abstraction reactions responsible for the oxidative degradation of organic solvents. The activation and conversion of the peroxide dianion by CO2 is general. Exposure of solid lithium peroxide (Li2O2) to CO2 in polar aprotic organic media results in aggressive oxidation. These findings indicate that CO2 must not be introduced in conditions relevant to typical lithium-O2 cell configurations, as production of HOOCO2- and -O2COOCO2- during lithium-O2 cell cycling will lead to cell degradation via oxidation of organic electrolytes and other vulnerable cell components. PMID- 28989642 TI - Electrochemical control of the single molecule conductance of a conjugated bis(pyrrolo)tetrathiafulvalene based molecular switch. AB - As the field of unimolecular electronics develops, there is growing interest in the development of functionalised molecular wires, such as switches, which will allow for more complex molecular-scale circuits. To this end, a three redox state single molecule switch, 1, based on bis(pyrrolo)tetrathiafulvalene (BPTTF) has been designed, synthesised and investigated using scanning tunnelling microscopy break junction (STM-BJ) studies and quantum transport calculations. Oxidising the BPTTF unit increases its conjugation, which was anticipated to increase the molecular conductance of 1. By changing the redox state of 1 electrochemically it was possible to vary the single molecule conductance by more than an order of magnitude (from 10-5.2G0 to 10-3.8G0). Simulations afforded a qualitatively similar trend. An additional, higher conductance feature is present in most traces at junction sizes of around 2.0 nm - further extension affords the switchable lower conductance feature at junction sizes closer to the molecular length (ca. 3.0 nm). Analysis of the conductance traces shows that these two conductance features occur sequentially in nearly all junctions. This behaviour is attributed to an alternative initial junction conformation in which one or more of the BPTTF sulfur atoms acts as an anchoring group. This hypothesis is supported by a computational study of binding conformations and STM-BJ studies on a model compound, 2, with only one thiol anchor. Our results indicate that the redox properties of BPTTF make it an excellent candidate for use in single molecule switches. PMID- 28989643 TI - Real single ion solvation free energies with quantum mechanical simulation. AB - Single ion solvation free energies are one of the most important properties of electrolyte solutions and yet there is ongoing debate about what these values are. Only the values for neutral ion pairs are known. Here, we use DFT interaction potentials with molecular dynamics simulation (DFT-MD) combined with a modified version of the quasi-chemical theory (QCT) to calculate these energies for the lithium and fluoride ions. A method to correct for the error in the DFT functional is developed and very good agreement with the experimental value for the lithium fluoride pair is obtained. Moreover, this method partitions the energies into physically intuitive terms such as surface potential, cavity and charging energies which are amenable to descriptions with reduced models. Our research suggests that lithium's solvation free energy is dominated by the free energetics of a charged hard sphere, whereas fluoride exhibits significant quantum mechanical behavior that cannot be simply described with a reduced model. PMID- 28989644 TI - Unravelling the electronic structure and dynamics of an isolated molecular rotary motor in the gas-phase. AB - Light-driven molecular motors derived from chiral overcrowded alkenes are an important class of compounds in which sequential photochemical and thermal rearrangements result in unidirectional rotation of one part of the molecule with respect to another. Here, we employ anion photoelectron spectroscopy to probe the electronic structure and dynamics of a unidirectional molecular rotary motor anion in the gas-phase and quantum chemistry calculations to guide the interpretation of our results. We find that following photoexcitation of the first electronically excited state, the molecule rotates around its axle and some population remains on the excited potential energy surface and some population undergoes internal conversion back to the electronic ground state. These observations are similar to those observed in time-resolved measurements of rotary molecular motors in solution. This work demonstrates the potential of anion photoelectron spectroscopy for studying the electronic structure and dynamics of molecular motors in the gas-phase, provides important benchmarks for theory and improves our fundamental understanding of light-activated molecular rotary motors, which can be used to inform the design of new photoactivated nanoscale devices. PMID- 28989645 TI - Thermochemical functionalisation of graphenes with minimal framework damage. AB - Graphene and graphene nanoplatelets can be functionalised via a gas-phase thermochemical method; the approach is versatile, readily scalable, and avoids the introduction of additional defects by exploiting existing sites. Direct TEM imaging confirmed covalent modification of single layer graphene, without damaging the connectivity of the lattice, as supported by Raman spectrometry and AFM nano-indentation measurements of mechanical stiffness. The grafting methodology can also be applied to commercially-available bulk graphene nanoplatelets, as illustrated by the preparation of anionic, cationic, and non ionic derivatives. Successful bulk functionalisation is evidenced by TGA, Raman, and XPS, as well as in dramatic changes in aqueous dispersability. Thermochemical functionalisation thus provides a facile approach to modify both graphene monolayers, and a wide range of graphene-related nanocarbons, using variants of simple CVD equipment. PMID- 28989646 TI - The double-edged role of copper in the fate of amyloid beta in the presence of anti-oxidants. AB - The biological fate of amyloid beta (Abeta) species is a fundamental question in Alzheimer's disease (AD) pathogenesis. The competition between clearance and aggregation of Abetas is critical for the onset of AD. Copper has been widely considered to be an inducer of harmful crosslinking of Abetas, and an important triggering factor for the onset of AD. In this report, however, we present data to show that copper can also be an inducer of Abeta degradation in the presence of a large excess of well-known intrinsic (such as dopamine) or extrinsic (such as vitamin C) anti-oxidants. The degraded fragments were identified using SDS Page gels, and validated via nanoLC-MS/MS. A tentative mechanism for the degradation was proposed and validated with model peptides. In addition, we performed electrophysiological analysis to investigate the synaptic functions in brain slices, and found that in the presence of a significant excess of vitamin C, Cu(ii) could prevent an Abeta-induced deficit in synaptic transmission in the hippocampus. Collectively, our evidence strongly indicated that a proper combination of copper and anti-oxidants might have a positive effect on the prevention of AD. This double-edged function of copper in AD has been largely overlooked in the past. We believe that our report is very important for fully understanding the function of copper in AD pathology. PMID- 28989647 TI - Heterocyclic boronic acids display sialic acid selective binding in a hypoxic tumor relevant acidic environment. AB - Boronic acids are well known for their ability to reversibly interact with the diol groups found in sugars and glycoproteins. However, they are generally indiscriminate in their binding. Herein we describe the discovery of a group of heterocyclic boronic acids demonstrating unusually high affinity and selectivity for sialic acids (SAs or N-acetylneuraminic acid), which are sugar residues that are intimately linked with tumor growth and cancer progression. Remarkably, these interactions strengthen under the weakly acidic pH conditions associated with a hypoxic tumoral microenvironment. In vitro competitive binding assays uncovered a significantly higher ability of 5-boronopicolinic acid, one of the derivatives identified in this work as a strong SA-binder, to interact with cell surface SA in comparison to a gold-standard structure, 3-propionamidophenylboronic acid, which has proven to be an efficient SA-binder in numerous reports. This structure also proved to be suitable for further chemical conjugation with a well-preserved SA-binding capability. These findings suggest an attractive alternative to other ongoing boronic acid based chemistry techniques aiming to achieve tumor-specific chemotherapies and diagnoses. PMID- 28989649 TI - Quinone-fused porphyrins as contrast agents for photoacoustic imaging. AB - Photoacoustic (PA) imaging is an emerging non-invasive diagnostic modality with many potential clinical applications in oncology, rheumatology and the cardiovascular field. For this purpose, there is a high demand for exogenous contrast agents with high absorption coefficients in the optical window for tissue imaging, i.e. the near infrared (NIR) range between 680 and 950 nm. We herein report the photoacoustic properties of quinone-fused porphyrins inserted with different transition metals as new highly promising candidates. These dyes exhibit intense NIR absorption, a lack of fluorescence emission, and PA sensitivity in concentrations below 3 nmol mL-1. In this context, the highest PA signal was obtained with a Zn(ii) inserted dye. Furthermore, this dye was stable in blood serum and free thiol solution and exhibited negligible cell toxicity. Additionally, the Zn(ii) probe could be detected with an up to 3.2 fold higher PA intensity compared to the clinically most commonly used PA agent, ICG. Thus, further exploration of the 'quinone-fusing' approach to other chromophores may be an efficient way to generate highly potent PA agents that do not fluoresce and shift their absorption into the NIR range. PMID- 28989648 TI - Self-assembling soft structures for intracellular NO release and promotion of neurite outgrowth. AB - Nitric oxide (NO), an endogenously produced free radical species, is an extremely important signalling molecule in several biochemical processes related to neurotransmission, neuronal communication, and vasodilation, to name a few. Other than relying on endogenous synthesis, intracellular NO delivery presents an interesting challenge to fully exploit the therapeutic potential of this gaseous molecule. We have applied a self-assembling peptide conjugate strategy to devise a construct carrying a NO-release arm, which can be activated under standard redox conditions. Consequently, a tryptophan-based peptide carrier was designed, which self-assembled in the solution phase to afford soft nanospherical structures, and released NO in Neuro2a cell line, resulting in neurite outgrowth. PMID- 28989650 TI - Thiol-ene click chemistry: a biocompatible way for orthogonal bioconjugation of colloidal nanoparticles. AB - Bioconjugation based on crosslinking primary amines to carboxylic acid groups has found broad applications in protein modification, drug development, and nanomaterial functionalization. However, proteins, which are made up of amino acids, typically give nonselective bioconjugation when using primary amine-based crosslinking. In order to control protein orientation and activity after conjugation, selective bioconjugation is desirable. We herein report an efficient and cysteine-selective thiol-ene click reaction-based bioconjugation strategy using colloidal nanoparticles. The resulting thiol-ene based aptamer and enzyme nanoconjugates demonstrated excellent target binding ability and enzymatic activity, respectively. Thus, thiol-ene click chemistry can provide a stable and robust crosslinker in a biocompatible manner for bioconjugation of any thiol containing biomolecule with nanomaterials. This will open more opportunities for applications of thiol-ene reactions and functional colloidal nanoparticles in chemical biology. PMID- 28989651 TI - Fluorometric probing of the lipase level as acute pancreatitis biomarkers based on interfacially controlled aggregation-induced emission (AIE). AB - As a sudden inflammation of the pancreas, acute pancreatitis presents severe complications and a high mortality rate, despite treatment. Lipase in serum serves as an essential biomarker of acute pancreatitis and even pancreatic cancer. Therefore, developing robust, convenient and sensitive probing of lipase levels is greatly needed. In this work, we present glutamate functionalized tetraphenylethylene (TPE) as a "turn-on" fluorescent probe (S1) based on the aggregation-induced emission (AIE) mechanism for lipase levels with new recognition units. In heterogeneous media, the hydrophilic amino and carboxyl groups in the probe were specifically introduced to facilitate its full access to lipase at the oil-water interface and achieve an interfacially controlled AIE process. The linear response of fluorescence ranging from 0 to 80 U L-1, which included the concentration range of the lipase level in human serum, considering the dilution factor if necessary, the limit of detection as low as 0.13 U L-1, and the fast response time (7 min) were determined. The value of the apparent Michaelis-Menten constant (Km) was obtained as 4.23 MUM, which indicated superior affinity between lipase and the probe molecule. The selectivity, photostability, dynamic monitoring of the enzymatic reaction, and preliminary commercial enzyme activity screening were summarized. As far as we know, this is the fastest, easiest and most sensitive method for lipase level probing in the reported literature. Finally, probing the lipase level for the first time in real human serum samples was also conducted successfully. PMID- 28989652 TI - Elucidation of the relative and absolute stereochemistry of the kalimantacin/batumin antibiotics. AB - Kalimantacin A and batumin exhibit potent and selective antibiotic activity against Staphylococcus species including MRSA. Both compounds are formed via a hybrid polyketide synthase/non-ribosomal peptide synthetase (PKS-NRPS) biosynthetic pathway and from comparison of the gene clusters it is apparent that batumin from Pseudomonas batumici and kalimantacin from P. fluorescens are the same compound. The linear structure of this unsaturated acid was assigned by spectroscopic methods, but the relative and absolute stereochemistry of the five stereocentres remained unknown. Herein we describe isolation of kalimantacin A and two further metabolites 17,19-diol 2 and 27-descarbomyl hydroxyketone 3 from cultures of P. fluorescens. Their absolute and relative stereochemistries are rigorously determined using a multidisciplinary approach combining natural product degradation and fragment synthesis with bioinformatics and NMR spectroscopy. Diol 2 has the 5R, 15S, 17S, 19R, 26R, 27R configuration and is the immediate biosynthetic precursor of the bioactive kalimantacin A formed by oxidation of the 17-alcohol to the ketone. PMID- 28989653 TI - Bioinspired enantioselective synthesis of crinine-type alkaloids via iridium catalyzed asymmetric hydrogenation of enones. AB - A bioinspired enantioselective synthesis of crinine-type alkaloids has been developed by iridium-catalyzed asymmetric hydrogenation of racemic cycloenones. The method features a biomimetic stereodivergent resolution of the substrates bearing a remote arylated quaternary stereocenter. Using this protocol, 24 crinine-type alkaloids and 8 analogues were synthesized in a concise and rapid way with high yield and high enantioselectivity. PMID- 28989654 TI - Assessing crystal field and magnetic interactions in diuranium-MU-chalcogenide triamidoamine complexes with UIV-E-UIV cores (E = S, Se, Te): implications for determining the presence or absence of actinide-actinide magnetic exchange. AB - We report the synthesis and characterisation of a family of diuranium(iv)-MU chalcogenide complexes including a detailed examination of their electronic structures and magnetic behaviours. Treatment of [U(TrenTIPS)] [1, TrenTIPS = N(CH2CH2NSiPri3)3] with Ph3PS, selenium or tellurium affords the diuranium(iv) sulfide, selenide, and telluride complexes [{U(TrenTIPS)}2(MU-E)] (E = S, 2; Se, 5; Te, 6). Complex 2 is also formed by treatment of [U(TrenTIPS){OP(NMe2)3}] (3) with Ph3PS, whereas treatment of 3 with elemental sulfur gives the diuranium(iv) persulfido complex [{U(TrenTIPS)}2(MU-eta2:eta2-S2)] (4). Complexes 2-6 have been variously characterised by single crystal X-ray diffraction, NMR, IR, and optical spectroscopies, room temperature Evans and variable temperature SQUID magnetometry, elemental analyses, and complete active space self consistent field spin orbit calculations. The combined characterisation data present a self consistent picture of the electronic structure and magnetism of 2, 5, and 6, leading to the conclusion that single-ion crystal field effects, and not diuranium magnetic coupling, are responsible for features in their variable temperature magnetisation data. The presence of magnetic coupling is often implied and sometimes quantified by such data, and so this study highlights the importance of evaluating other factors, such as crystal field effects, that can produce similar magnetic observables, and to thus avoid misassignments of such phenomena. PMID- 28989655 TI - Precision spherical nucleic acids for delivery of anticancer drugs. AB - We report a spherical nucleic acid (SNA) system for the delivery of BKM120, an anticancer drug for treatment of chronic lymphocytic leukemia (CLL). While promising for cancer treatment, this drug crosses the blood-brain barrier causing significant side-effects in patients. The DNA nanoparticle encapsulates BKM120 in high efficiency, and is unparalleled in its monodispersity, ease of synthesis and stability in different biological media and in serum. These DNA nanostructures demonstrate efficient uptake in human cervical cancer (HeLa) cells, and increased internalization of cargo. In vitro studies show that BKM120-loaded nanoparticles promote apoptosis in primary patient CLL lymphocytes, and act as sensitizers of other antitumor drugs, without causing non-specific inflammation. Evaluation of this drug delivery system in vivo shows long circulation times up to 24 hours, full body distribution, accumulation at tumor sites and minimal leakage through the blood-brain barrier. Our results demonstrate the great potential of these delivery vehicles as a general platform for chemotherapeutic drug delivery. PMID- 28989657 TI - Selective cobalt nanoparticles for catalytic transfer hydrogenation of N heteroarenes. AB - Nitrogen modified cobalt catalysts supported on carbon were prepared by pyrolysis of the mixture generated from cobalt(ii) acetate in aqueous solution of melamine or waste melamine resins, which are widely used as industrial polymers. The obtained nanostructured materials catalyze the transfer hydrogenation of N heteroarenes with formic acid in the absence of base. The optimal Co/Melamine-2@C 700 catalyst exhibits high activity and selectivity for the dehydrogenation of formic acid into molecular hydrogen and carbon dioxide and allows for the reduction of diverse N-heteroarenes including substrates featuring sensitive functional groups. PMID- 28989656 TI - Computational investigation of O2 diffusion through an intra-molecular tunnel in AlkB; influence of polarization on O2 transport. AB - E. Coli AlkB catalyzes the direct dealkylation of various alkylated bases in damaged DNA. The diffusion of molecular oxygen to the active site in AlkB is an essential step for the oxidative dealkylation activity. Despite detailed studies on the stepwise oxidation mechanism of AlkB, there is no conclusive picture of how O2 molecules reach the active site of the protein. Yu et al. (Nature, 439, 879) proposed the existence of an intra-molecular tunnel based on their initial crystal structures of AlkB. We have employed computational simulations to investigate possible migration pathways inside AlkB for O2 molecules. Extensive molecular dynamics (MD) simulations, including explicit ligand sampling and potential of mean force (PMF) calculations, have been performed to provide a microscopic description of the O2 delivery pathway in AlkB. Analysis of intra molecular tunnels using the CAVER software indicates two possible pathways for O2 to diffuse into the AlkB active site. Explicit ligand sampling simulations suggests that only one of these tunnels provides a viable route. The free energy path for an oxygen molecule to travel along each of these tunnels has been determined with AMBER and AMOEBA. Both PMFs indicate passive transport of O2 from the surface of the protein. However, the inclusion of explicit polarization shows a very large barrier for diffusion of the co-substrate out of the active site, compared with the non-polarizable potential. In addition, our results suggest that the mutation of a conserved residue along the tunnel, Y178, has dramatic effects on the dynamics of AlkB and on the transport of O2 along the tunnel. PMID- 28989658 TI - Efficient syntheses of (-)-crinine and (-)-aspidospermidine, and the formal synthesis of (-)-minfiensine by enantioselective intramolecular dearomative cyclization. AB - Polycyclic alkaloids bearing all-carbon quaternary centers possess a diversity of biological activities and are challenging targets in natural product synthesis. The development of a general and asymmetric catalytic method applicable to the efficient syntheses of a series of complex polycyclic alkaloids remains highly desirable in synthetic chemistry. Herein we describe an efficient palladium catalyzed enantioselective dearomative cyclization which is capable of synthesizing two important classes of tricyclic nitrogen-containing skeleton, chiral dihydrophenanthridinone and dihydrocarbazolone derivatives bearing all carbon quaternary centers, in excellent yields and enantioselectivities. The P chiral monophosphorus ligand AntPhos is crucial for the reactivity and enantioselectivity, and the choice of the N-phosphoramide protecting group is essential for the desired chemoselectivity. This method has enabled the enantioselective total syntheses of three distinctive and challenging biologically important polycyclic alkaloids, specifically a concise and gram scale synthesis of (-)-crinine, an efficient synthesis of indole alkaloid (-) aspidospermidine and a formal enantioselective synthesis of (-)-minfiensine. PMID- 28989659 TI - A multi-signal fluorescent probe for simultaneously distinguishing and sequentially sensing cysteine/homocysteine, glutathione, and hydrogen sulfide in living cells. AB - Biothiols, which have a close network of generation and metabolic pathways among them, are essential reactive sulfur species (RSS) in the cells and play vital roles in human physiology. However, biothiols possess highly similar chemical structures and properties, resulting in it being an enormous challenge to simultaneously discriminate them from each other. Herein, we develop a unique fluorescent probe (HMN) for not only simultaneously distinguishing Cys/Hcy, GSH, and H2S from each other, but also sequentially sensing Cys/Hcy/GSH and H2S using a multi-channel fluorescence mode for the first time. When responding to the respective biothiols, the robust probe exhibits multiple sets of fluorescence signals at three distinct emission bands (blue-green-red). The new probe can also sense H2S at different concentration levels with changes of fluorescence at the blue and red emission bands. In addition, the novel probe HMN is able to discriminate and sequentially sense biothiols in biological environments via three-color fluorescence imaging. We expect that the development of the robust probe HMN will provide a powerful strategy to design fluorescent probes for the discrimination and sequential detection of biothiols, and offer a promising tool for exploring the interrelated roles of biothiols in various physiological and pathological conditions. PMID- 28989660 TI - Rh-catalyzed aerobic oxidative cyclization of anilines, alkynes, and CO. AB - Transition-metal-catalyzed oxidative C-H cyclization of anilines has been an attractive and powerful strategy for the efficient construction of N heterocycles. However, primary and tertiary anilines are rarely employed in this strategy due to the relative instability with strong oxidants or the presence of three C-N bonds. We describe here a novel Rh-catalyzed C-H cyclization of a wide range of anilines with alkynes and CO, using an aerobic oxidative protocol. Particularly, the simple primary anilines and readily prepared tertiary anilines could be easily converted to quinolin-2(1H)-ones, which are high value-added, biologically significant N-heterocycles, via C-N bond cleavage. PMID- 28989661 TI - Completing the series of boron-nucleophilic cyanoborates: boryl anions of type NHC-B(CN)2. AB - Since the first seminal report of boron-centred nucleophiles, the area of boryl anions has developed only sporadically and requires further systematisation. The boryl anions of type NHC-B(CN)2- (NHC = N-heterocyclic carbene) described herein complete a consistent series with the known anions cAAC-B(CN)2- [cAAC = cyclic(alkyl)(amino)carbene] and B(CN)32-. A novel approach towards NHC stabilised cyanoboranes based on alkylthio-cyano exchange at boron is presented, and in contrast to other methods affords the products in better purity and yield. Reduction of suitable NHC-dicyanoboranes gave two unprecedented examples of NHC B(CN)2- boryl anions. The latter were shown to react as boron-centred nucleophiles with facile formation of B-E bonds, where E = C, Si, Sn, P, Au. Bonding analysis by DFT calculations suggests a systematic variation of the energy of the boron-centred HOMO depending on the carbene, which in turn can control the nucleophilic character. PMID- 28989663 TI - Impact of mechanical bonding on the redox-switching of tetrathiafulvalene in crown ether-ammonium [2]rotaxanes. AB - Switchable crown ether-ammonium [2]rotaxanes with a redox-active tetrathiafulvalene (TTF) unit implemented in their wheels were synthesised and fully characterised. Reversible operation in two modes is possible, in which the [2]rotaxane's axle is either charged or neutral. Cyclic voltammetry experiments reveal the effects of mechanical bonding on the electrochemical properties of TTF and show the [2]rotaxanes to perform a distinct function in both modes. In the charged mode, redox-switching is dominated by strong electrostatic repulsion in the [2]rotaxane which subsequently leads to a macrocycle translation along the axle. In the non-charged mode, a selective energetic stabilisation of TTF radical cations is observed, which can be attributed to an interplay of weak electrostatic interactions between wheel and axle. PMID- 28989664 TI - A new function for thermal phase transition-based polymer actuators: autonomous motion on a surface of constant temperature. AB - It is very challenging to make materials capable of autonomous oscillation known in many living systems (such as the heartbeat). Herein, we describe an approach to creating a thermo-mechano-thermal feedback loop for thermal phase transition based polymer actuators, which leads to hour-long, autonomous motion on a substrate surface of constant temperature. We investigated the variables that determine the amplitude and period of the motion, and demonstrated exemplary physical work powered by direct thermomechanical energy conversion. Such continuous motion of a solid polymer driven by thermal energy without the need for temperature up/down switching is unprecedented, and the validated feedback loop can be implemented into other thermal phase transition-based polymer actuators. PMID- 28989662 TI - AIE-doped poly(ionic liquid) photonic spheres: a single sphere-based customizable sensing platform for the discrimination of multi-analytes. AB - By simultaneously exploiting the unique properties of ionic liquids and aggregation-induced emission (AIE) luminogens, as well as photonic structures, a novel customizable sensing system for multi-analytes was developed based on a single AIE-doped poly(ionic liquid) photonic sphere. It was found that due to the extraordinary multiple intermolecular interactions involved in the ionic liquid units, one single sphere could differentially interact with broader classes of analytes, thus generating response patterns with remarkable diversity. Moreover, the optical properties of both the AIE luminogen and photonic structure integrated in the poly(ionic liquid) sphere provide multidimensional signal channels for transducing the involved recognition process in a complementary manner and the acquisition of abundant and sufficient sensing information could be easily achieved on only one sphere sensor element. More importantly, the sensing performance of our poly(ionic liquid) photonic sphere is designable and customizable through a simple ion-exchange reaction and target-oriented multi analyte sensing can be conveniently realized using a selective receptor species, such as counterions, showing great flexibility and extendibility. The power of our single sphere-based customizable sensing system was exemplified by the successful on-demand detection and discrimination of four multi-analyte challenge systems: all 20 natural amino acids, nine important phosphate derivatives, ten metal ions and three pairs of enantiomers. To further demonstrate the potential of our spheres for real-life application, 20 amino acids in human urine and their 26 unprecedented complex mixtures were also discriminated between by the single sphere-based array. PMID- 28989665 TI - Full color palette of fluorescent d-amino acids for in situ labeling of bacterial cell walls. AB - Fluorescent d-amino acids (FDAAs) enable efficient in situ labeling of peptidoglycan in diverse bacterial species. Conducted by enzymes involved in peptidoglycan biosynthesis, FDAA labeling allows specific probing of cell wall formation/remodeling activity, bacterial growth and cell morphology. Their broad application and high biocompatibility have made FDAAs an important and effective tool for studies of peptidoglycan synthesis and dynamics, which, in turn, has created a demand for the development of new FDAA probes. Here, we report the synthesis of new FDAAs, with emission wavelengths that span the entire visible spectrum. We also provide data to characterize their photochemical and physical properties, and we demonstrate their utility for visualizing peptidoglycan synthesis in Gram-negative and Gram-positive bacterial species. Finally, we show the permeability of FDAAs toward the outer-membrane of Gram-negative organisms, pinpointing the probes available for effective labeling in these species. This improved FDAA toolkit will enable numerous applications for the study of peptidoglycan biosynthesis and dynamics. PMID- 28989667 TI - A combined experimental and theoretical spectroscopic protocol for determination of the structure of heterogeneous catalysts: developing the information content of the resonance Raman spectra of M1 MoVO x. AB - Absorption and multiwavelength resonance Raman spectroscopy are widely used to investigate the electronic structure of transition metal centers in coordination compounds and extended solid systems. In combination with computational methodologies that have predictive accuracy, they define powerful protocols to study the spectroscopic response of catalytic materials. In this work, we study the absorption and resonance Raman spectra of the M1 MoVO x catalyst. The spectra were calculated by time-dependent density functional theory (TD-DFT) in conjunction with the independent mode displaced harmonic oscillator model (IMDHO), which allows for detailed bandshape predictions. For this purpose cluster models with up to 9 Mo and V metallic centers are considered to represent the bulk structure of MoVO x . Capping hydrogens were used to achieve valence saturation at the edges of the cluster models. The construction of model structures was based on a thorough bonding analysis which involved conventional DFT and local coupled cluster (DLPNO-CCSD(T)) methods. Furthermore the relationship of cluster topology to the computed spectral features is discussed in detail. It is shown that due to the local nature of the involved electronic transitions, band assignment protocols developed for molecular systems can be applied to describe the calculated spectral features of the cluster models as well. The present study serves as a reference for future applications of combined experimental and computational protocols in the field of solid-state heterogeneous catalysis. PMID- 28989666 TI - Development of a high quantum yield dye for tumour imaging. AB - A fluorescent dye, FEB, with high fluorescence quantum yield for tumour imaging is reported. FEB dyes can be efficiently synthesized in three steps and then easily modified with either PEG or PEG-iRGD to yield FEB-2000 or FEB-2000-iRGD, respectively. Both modified dyes showed negligible toxicity and were thus able to be adopted for in vivo tumour imaging. PEG modification endowed the dye FEB-2000 with both long circulating times and good tumour targeting properties in a MDA-MB 231 xenograft model. Further conjugation with iRGD to generate FEB-2000-iRGD showed minimal targeting enhancement. These results provide a template for the efficient preparation of FEB dyes for use in tumour imaging, thus providing a foundation for future modifications. PMID- 28989668 TI - Micellar catalysis-enabled sustainable ppm Au-catalyzed reactions in water at room temperature. AB - Several ppm level gold-catalyzed reactions enabled by the ligand HandaPhos can be performed at room temperature in aqueous nanoreactors composed of the surfactant Nok. Variously substituted allenes undergo cycloisomerization leading to heterocyclic products in good yields. Likewise, cyclodehydration is also illustrated under similar conditions, as is an intermolecular variant, hydration of terminal alkynes. Recycling of the catalyst and reaction medium is also illustrated. A low E factor associated with limited solvent use and therefore, waste generation, documents the greenness of this process. PMID- 28989669 TI - Metal-free di- and tri-fluoromethylation of alkenes realized by visible-light induced perylene photoredox catalysis. AB - Regioselective amino-difluoromethylation of aromatic alkenes via C(sp3)-CF2H and C(sp3)-N bond formation with the C 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 1111111111111111111111111111111111 1111111111111111111111111111111111 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 1111111111111111111111111111111111 1111111111111111111111111111111111 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 C moiety has been achieved in a single operation by visible-light photoredox catalysis. The combination of a shelf stable and easy-to-handle sulfonium salt, S-difluoromethyl-S-di(p-xylyl)sulfonium tetrafluoroborate, and perylene catalysis is the key to the successful transformation. Furthermore, this noble metal-free protocol allows for the photocatalytic trifluoromethylation of alkenes. PMID- 28989671 TI - Highly efficient enantioselective liquid-liquid extraction of 1,2-amino-alcohols using SPINOL based phosphoric acid hosts. AB - Access to enantiopure compounds on large scale in an environmentally friendly and cost-efficient manner remains one of the greatest challenges in chemistry. Resolution of racemates using enantioselective liquid-liquid extraction has great potential to meet that challenge. However, a relatively feeble understanding of the chemical principles and physical properties behind this technique has hampered the development of hosts possessing sufficient resolving power for their application to large scale processes. Herein we present, employing the previously untested SPINOL based phosphoric acids host family, an in depths study of the parameters affecting the efficiency of the resolution of amino-alcohols in the optic of further understanding the core principles behind ELLE. We have systematically investigated the dependencies of the enantioselection by parameters such as the choice of solvent, the temperature, as well as the pH and bring to light many previously unsuspected and highly intriguing interactions. Furthermore, utilizing these new insights to our advantage, we developed novel, highly efficient, extraction and resolving protocols which provide remarkable levels of enantioselectivity. It was shown that the extraction is catalytic in host by demonstrating transport in a U-tube and finally it was demonstrated how the solvent dependency could be exploited in an unprecedented triphasic resolution system. PMID- 28989670 TI - Potent mechanism-based sirtuin-2-selective inhibition by an in situ-generated occupant of the substrate-binding site, "selectivity pocket" and NAD+-binding site. AB - Sirtuin 2 (SIRT2), a member of the NAD+-dependent histone deacetylase family, has recently received increasing attention due to its potential involvement in neurodegenerative diseases and the progression of cancer. Potent and selective SIRT2 inhibitors thus represent desirable biological probes. Based on the X-ray crystal structure of SIRT2 in complex with a previously reported weak inhibitor (6), we identified in this study the potent mechanism-based inactivator KPM-2 (36), which is selective toward SIRT2. Compound 36 engages in a nucleophilic attack toward NAD+ at the active site of SIRT2, which affords a stable 36-ADP ribose conjugate that simultaneously occupies the substrate-binding site, the "selectivity pocket" and the NAD+-binding site. Moreover, 36 exhibits antiproliferative activity in cancer cells and remarkable neurite outgrowth activity. This strategy for the selective inhibition of SIRT2 should allow further probing of the biology of SIRT2, and promote the development of new disease treatment strategies. PMID- 28989672 TI - Photochromic coenzyme Q derivatives: switching redox potentials with light. AB - Coenzyme Q is an important redox cofactor involved in a variety of cellular processes, and is thus found in several cell compartments. We report a photochromic derivative of coenzyme Q that combines the molecular structures of the redox active cofactor and a photochromic dye. Light irradiation triggers an electronic rearrangement reversibly changing the redox potential. We used this effect to control the intermolecular redox reaction of the photochromic coenzyme Q derivative with dihydropyridine in solution by light irradiation. On mitochondria, the altered redox properties showed an effect on the respiratory chain. The experiments demonstrate that the redox reactions can be initiated inside the system of interest through irradiation with light and the accompanied photoisomerization. PMID- 28989673 TI - Predicting allosteric mutants that increase activity of a major antibiotic resistance enzyme. AB - The CTX-M family of beta lactamases mediate broad-spectrum antibiotic resistance and are present in the majority of drug-resistant Gram-negative bacterial infections worldwide. Allosteric mutations that increase catalytic rates of these drug resistance enzymes have been identified in clinical isolates but are challenging to predict prospectively. We have used molecular dynamics simulations to predict allosteric mutants increasing CTX-M9 drug resistance, experimentally testing top mutants using multiple antibiotics. Purified enzymes show an increase in catalytic rate and efficiency, while mutant crystal structures show no detectable changes from wild-type CTX-M9. We hypothesize that increased drug resistance results from changes in the conformational ensemble of an acyl intermediate in hydrolysis. Machine-learning analyses on the three top mutants identify changes to the binding-pocket conformational ensemble by which these allosteric mutations transmit their effect. These findings show how molecular simulation can predict how allosteric mutations alter active-site conformational equilibria to increase catalytic rates and thus resistance against common clinically used antibiotics. PMID- 28989674 TI - High turnover in electro-oxidation of alcohols and ethers with a glassy carbon supported phenanthroimidazole mediator. AB - Glassy carbon electrodes covalently modified with a phenanthroimidazole mediator promote electrochemical alcohol and ether oxidation: three orders of magnitude increase in TON, to ~15 000 in each case, was observed compared with homogeneous mediated reactions. We propose the deactivation pathways in homogeneous solution are prevented by the immobilization: modified electrode reversibility is increased for a one-electron oxidation reaction. The modified electrodes were used to catalytically oxidize p-anisyl alcohol and 1-((benzyloxy)methyl)-4 methoxybenzene, selectively, to the corresponding benzaldehyde and benzyl ester, respectively. PMID- 28989675 TI - Atmospheric pressure neutral reionization mass spectrometry for structural analysis. AB - Ion dissociation is the usual basis for tandem MS analysis but a significant limitation is that only charged fragments from ion dissociation events are detected while neutral fragments are simply lost. This study reports our continued effort to solve this problem by developing atmospheric pressure neutral reionization mass spectrometry (APNR). In APNR, analyte ions are thermally dissociated (atmospheric pressure thermal dissociation, APTD) followed by soft reionization using electrosonic spray ionization (ESSI). Our results show that APNR is a powerful method for structural analysis of various biomolecules such as peptides, saccharides and nucleotides, as well as for elucidating unimolecular ion dissociation mechanisms. It was found that APNR provides extensive fragment ions including a series of y ions in peptides, which benefit sequencing and provide complementary information to collision induced dissociation (CID). In particular, direct cleavage of disulfide bonds of peptides occurs during APTD, facilitating peptide sequencing and disulfide bond mapping. In addition, many cross-ring cleavage fragments are detected during APNR analysis of oligosaccharides, indicating that the APTD dissociation process is energetic and potentially useful for identifying glycan linkage sites. Fragmentation patterns of oligosaccharide isomers can be used for their differentiation. Furthermore, in the cases of dissociation of nucleotides and synthetic naphthoylindole drugs, the putative neutral, phosphorylated riboses and indoles, were successfully detected using APNR, providing strong evidence to confirm previously proposed unimolecular ion dissociation mechanisms. We believe this APNR technique along with APTD should be of high value in structure determination of biomolecules. PMID- 28989676 TI - Rapid determination of medulloblastoma subgroup affiliation with mass spectrometry using a handheld picosecond infrared laser desorption probe. AB - Medulloblastoma (MB), the most prevalent malignant childhood brain tumour, consists of at least 4 distinct subgroups each of which possesses a unique survival rate and response to treatment. To rapidly determine MB subgroup affiliation in a manner that would be actionable during surgery, we subjected murine xenograft tumours of two MB subgroups (SHH and Group 3) to Mass Spectrometry (MS) profiling using a handheld Picosecond InfraRed Laser (PIRL) desorption probe and interface developed by our group. This platform provides real time MS profiles of tissue based on laser desorbed lipids and small molecules with only 5-10 seconds of sampling. PIRL-MS analysis of ex vivo MB tumours offered a 98% success rate in subgroup determination, observed over 194 PIRL-MS datasets collected from 19 independent tumours (~10 repetitions each) utilizing 6 different established MB cell lines. Robustness was verified by a 5% leave-out-and-remodel test. PIRL ablated tissue material was collected on a filter paper and subjected to high resolution LC-MS to provide ion identity assignments for the m/z values that contribute most to the statistical discrimination between SHH and Group 3 MB. Based on this analysis, rapid classification of MB with PIRL-MS utilizes a variety of fatty acid chains, glycerophosphates, glycerophosphoglycerols and glycerophosphocholines rapidly extracted from the tumours. In this work, we provide evidence that 5-10 seconds of sampling from ex vivo MB tissue with PIRL-MS can allow robust tumour subgroup classification, and have identified several biomarker ions responsible for the statistical discrimination of MB Group 3 and the SHH subgroup. The existing PIRL MS platform used herein offers capabilities for future in vivo use. PMID- 28989677 TI - Catalytic [2 + 2 + 2] cycloaddition with indium(iii)-activated formaldimines: a practical and selective access to hexahydropyrimidines and 1,3-diamines from alkenes. AB - Catalytic [2 + 2 + 2] cycloaddition with imines has, for the first time, been developed as a practical and selective approach for direct construction of hexahydropyrimidine derivatives from various alkenes. With formaldimines as reagents and simple InCl3 as the catalyst, this ionic [2 + 2 + 2] approach is applicable for a wide scope of alkenes and allenes with various electronic and steric properties, as well as substitution patterns. Through facile hydrolysis of the resulting hexahydropyrimidines, this catalytic process also provides a new synthetic strategy for the aminomethylamination of alkenes and allenes to practically access 1,3-diamine derivatives. PMID- 28989678 TI - Suzuki-Miyaura cross-coupling of amides and esters at room temperature: correlation with barriers to rotation around C-N and C-O bonds. AB - The Suzuki-Miyaura cross-coupling has been widely recognized as one of the most important methods for the construction of C-C bonds. However, in contrast to traditional aryl halide or pseudohalide electrophiles, coupling reactions with unactivated C-N and C-O electrophiles have proven significantly more challenging. Here we report the first general palladium-catalyzed Suzuki-Miyaura cross coupling of both common amides and aryl esters through the selective cleavage of the C-N and C-O bonds under exceedingly mild conditions. Notably, for the first time we demonstrate selective C(acyl)-N and C(acyl)-O cleavage/cross-coupling under the same reaction conditions. The reaction uses a commercially available, bench-stable and operationally-convenient (eta3-1-t-Bu-indenyl)Pd(IPr)(Cl) precatalyst. Furthermore, we demonstrate that the reactivity of generic amides and aryl esters can be correlated with barriers to isomerization around the C(acyl)-X (X = N, O) bond, thus providing a blueprint for the development of a broad range of novel coupling reactions of ester and amide electrophiles by the selective activation of C-O and C-N bonds. PMID- 28989679 TI - From imine to amine: an unexpected left turn. Cis-beta iron(ii) PNNP' precatalysts for the asymmetric transfer hydrogenation of acetophenone. AB - A novel PNN ligand bearing an orthophenylene group and a primary amine was synthesized with the aid of a palladium-catalyzed amination and reacted with phosphonium dimers [-PR2CH2CH(OH)-]2[Br]2 R = Et, iPr, Cy, Ph, xylyl, and o-Tol, and [Fe(OH2)6]2+ to produce a new series of cis-beta iron(ii) PNNP' precatalysts cis-beta-[Fe(Br)(CO)(PNNP')]BPh4 as a pair of diastereomers. The more stable orthophenylene amido group was chosen to imitate and replace the enamido moiety of a highly active iron precatalyst for the asymmetric transfer hydrogenation (ATH) of ketones in an attempt to prevent its deactivation caused by reduction of the enamido group. This objective was partially achieved using the complex with a PEt2 group which catalyzed the transfer hydrogenation in isopropanol of 150 000 equivalents of acetophenone to racemic 1-phenylethanol. With a low acetophenone to catalyst ratio of 500 to 1, the catalytic activity was moderate and the enantiomeric excess (ee) of the product 1-phenylethanol ranged surprisingly from 94% (R) to 95% (S) depending on the nature of PR2 and whether the precatalyst contained an imine or amine donor. The amine precatalyst with a PEt2-group produced a more stable hydride species when activated, allowing the reaction mixture to be heated to 75 degrees C to obtain a TON of 8821 for acetophenone while retaining the high ee of 95% (S). The activation pathway in basic isopropanol (iPrOH) was studied for three precatalysts to elucidate that the cis beta precatalysts rearrange to form trans hydride complexes. The study suggests that the enantioselectivity of these complexes is determined by from which side of the PNNP' plane the hydride transfer occurs. PMID- 28989680 TI - A general and facile chemical avenue for the controlled and extreme regulation of water wettability in air and oil wettability under water. AB - The controlled modulation of both oil (under water) and water (in air) wettability is an emerging approach to develop several functional materials for various prospective applications including oil/water separation, anti-corrosive coatings, underwater robotics, protein crystallization, drug delivery, open microfluidics, water harvesting etc. Here, we report a 'reactive' and covalently cross-linked coating through a facile and robust Michael addition reaction, which is suitable for the controlled and extreme regulation of both water and oil wettability in air and under water respectively. Along with extremes (super philicity and super-phobicity) of water (in air) and oil (under water) wettability, this single multilayer construction was also able to display special liquid wettability (i.e.; extremely liquid repellent-but with controlled adhesive properties) both in air and under water, after strategic post chemical modifications, again through 1,4-conjugate addition reaction. The super-wetting properties in the materials were able to withstand various physical and chemical insults including adhesive tape test, sand drop test, and exposure to extremes of pH, salt, and surfactant contaminated aqueous media. Moreover, this approach also allowed the decoration of various flexible and rigid substrates (i.e.; wood, Al foil, synthetic fabric etc.) with various bio-inspired wettability properties including (1) non-adhesive superhydrophobicity (lotus leaf), (2) adhesive superhydrophobicity (rose petal), (3) underwater superoleophobicity (fish scale) etc. This single polymeric coating-which is capable of displaying several bio inspired interfaces both in air and under water, even after harsh physical/chemical insults-would be useful in various prospective and relevant applications for practical scenarios. PMID- 28989681 TI - Light-responsive paper strips as CO-releasing material with a colourimetric response. AB - Carbon monoxide (CO) is known for its multifaceted role in human physiology, and molecules that release CO in a controlled way have been proposed as therapeutic drugs. In this work, a light-responsive CO-releasing molecule (CORM-Dabsyl) showed a strong colourimetric response upon photochemical CO-release, owing to the tight conjugation of a Mn(i) tricarbonyl centre to a dabsyl chromophoric ligand (L). Whereas the complex was very stable in the dark in nitrogen-purged aqueous media, CO-release was effectively triggered using 405 nm irradiation. CORM-Dabsyl, L and the inactive product iCORM-Dabsyl have been investigated by DFT and TD-DFT calculations. Only mild toxicity of CORM-Dabsyl was observed against LX-2 and HepaRG(r) human cell lines (IC50 ~ 30 MUM). Finally, to develop a CO storage and release material that is readily applicable to therapeutic situations, CORM-Dabsyl was loaded on low-cost and easily disposable paper strips, from which the light triggered CO-release was conveniently visible with the naked eye. PMID- 28989682 TI - Interdomain flip-flop motion visualized in flavocytochrome cellobiose dehydrogenase using high-speed atomic force microscopy during catalysis. AB - Cellobiose dehydrogenase (CDH) is a dual domain flavocytochrome, which consists of a dehydrogenase (DH) domain containing a flavin adenine dinucleotide and a cytochrome (CYT) domain containing b-type heme. To directly visualize the dynamic domain motion of class-I CDH from Phanerochaete chrysosporium (PcCDH) during catalysis using high-speed atomic force microscopy, the apo-form of PcCDH was anchored to a heme-immobilized flat gold surface that can specifically fix the orientation of the CYT domain. The two domains of CDH are found to be immobile in the absence of cellobiose, whereas the addition of cellobiose triggers an interdomain flip-flop motion involving domain-domain association and dissociation. Our results indicate that dynamic motion of a dual domain enzyme during catalysis induces efficient electron transfer to an external electron acceptor. PMID- 28989683 TI - Enantioselective N-heterocyclic carbene-catalyzed nucleophilic dearomatization of alkyl pyridiniums. AB - NHC-catalyzed nucleophilic dearomatization of alkyl pyridiniums has been achieved to generate 1,4-dihydropyridines with high enantioselectivity. This is a rare example of catalytic, asymmetric addition of a nucleophile to the activated pyridinium that prefers C-4 functionalization leading to the 1,4-dihydropyridine with high selectivity. PMID- 28989684 TI - The unexpected roles of sigma and pi orbitals in electron donor and acceptor group effects on the 13C NMR chemical shifts in substituted benzenes. AB - Effects of electron-donating (R = NH2) and electron-withdrawing (R = NO2) groups on 13C NMR chemical shifts in R-substituted benzene are investigated by molecular orbital analyses. The 13C shift substituent effect in ortho, meta, and para position is determined by the sigma bonding orbitals in the aryl ring. The pi orbitals do not explain the substituent effects in the NMR spectrum as conventionally suggested in textbooks. The familiar electron donating and withdrawing effects on the pi system by NH2 and NO2 substituents induce changes in the sigma orbital framework, and the 13C chemical shifts follow the trends induced in the sigma orbitals. There is an implicit dependence of the sigma orbital NMR shift contributions on the pi framework, via unoccupied pi* orbitals, due to the fact that the nuclear shielding is a response property. PMID- 28989685 TI - Tuning SpyTag-SpyCatcher mutant pairs toward orthogonal reactivity encryption. AB - Genetically encoded covalent peptide tagging technology, such as the SpyTag SpyCatcher reaction, has emerged as a unique way to do chemistry with proteins. Herein, we report the reactivity engineering of SpyTag-SpyCatcher mutant pairs and show that distinct reactivity can be encrypted for the same reaction based on protein sequences of high similarity. Valuable features, including high selectivity, inverse temperature dependence and (nearly) orthogonal reactivity, could be achieved based on as few as three mutations. This demonstrates the robustness of the SpyTag-SpyCatcher reaction and the plasticity of its sequence specificity, pointing to a family of engineered protein chemistry tools. PMID- 28989686 TI - Electrochemical maps and movies of the hydrogen evolution reaction on natural crystals of molybdenite (MoS2): basal vs. edge plane activity. AB - Two dimensional (2D) semiconductor materials, such as molybdenum disulfide (MoS2) have attracted considerable interest in a range of chemical and electrochemical applications, for example, as an abundant and low-cost alternative electrocatalyst to platinum for the hydrogen evolution reaction (HER). While it has been proposed that the edge plane of MoS2 possesses high catalytic activity for the HER relative to the "catalytically inert" basal plane, this conclusion has been drawn mainly from macroscale electrochemical (voltammetric) measurements, which reflect the "average" electrocatalytic behavior of complex electrode ensembles. In this work, we report the first spatially-resolved measurements of HER activity on natural crystals of molybdenite, achieved using voltammetric scanning electrochemical cell microscopy (SECCM), whereby pixel resolved linear-sweep voltammogram (LSV) measurements have allowed the HER to be visualized at multiple different potentials to construct electrochemical flux movies with nanoscale resolution. Key features of the SECCM technique are that characteristic surface sites can be targeted and analyzed in detail and, further, that the electrocatalyst area is known with good precision (in contrast to many macroscale measurements on supported catalysts). Through correlation of the local voltammetric response with information from scanning electron microscopy (SEM) and atomic force microscopy (AFM) in a multi-microscopy approach, it is demonstrated unequivocally that while the basal plane of bulk MoS2 (2H crystal phase) possesses significant activity, the HER is greatly facilitated at the edge plane (e.g., surface defects such as steps, edges or crevices). Semi-quantitative treatment of the voltammetric data reveals that the HER at the basal plane of MoS2 has a Tafel slope and exchange current density (J0) of ~120 mV per decade and 2.5 * 10-6 A cm-2 (comparable to polycrystalline Co, Ni, Cu and Au), respectively, while the edge plane has a comparable Tafel slope and a J0 that is estimated to be more than an order-of-magnitude larger (~1 * 10-4 A cm-2). Finally, by tracking the temporal evolution of water contact angle (WCA) after cleavage, it is shown that cathodic polarization has a 'self-cleaning' effect on the surface of MoS2, consistent with the time-independent (i.e., time after cleavage) HER voltammetric response. PMID- 28989687 TI - Preparation and characterization of chemically bonded argon-boroxol ring cation complexes. AB - The cation complexes [ArB3O4]+, [ArB3O5]+, [ArB4O6]+ and [ArB5O7]+ were prepared via a laser vaporization supersonic ion source in the gas phase. Their vibrational spectra were measured via mass-selected infrared photodissociation spectroscopy. Spectroscopy combined with quantum chemical calculations revealed that the [ArB3O5]+, [ArB4O6]+ and [ArB5O7]+ cation complexes have planar structures each involving an aromatic boroxol ring and an argon-boron covalent bond. In contrast, the [ArB3O4]+ cation is characterized to be a weakly bound complex with a B3O4+ chain structure. PMID- 28989688 TI - Photoredox mediated nickel catalyzed C(sp3)-H thiocarbonylation of ethers. AB - The first direct C(sp3)-H thiocarbonylation reaction is achieved by visible light photoredox/Ni dual catalysis. The thioester group of thiobenzoate is transferred to the alpha-oxy carbon of various cyclic/acyclic ethers, which is the opposite to the commonly expected chemical reactivity involving acyl group transfer via the weaker C(acyl)-S activation. Through mechanistic studies, we proposed that the reaction is initiated by photocatalytic reduction and fragmentation of the thioester into an acyl radical and a thiolate. A nickel complex binds to the thiolate and induces the decarbonylation of the acyl radical to form an aryl radical, which abstracts hydrogen from the alpha-oxy carbon of the ether. The resulting alpha-oxy C(sp3) centered radical re-binds to the (RS)(CO)Ni complex, which undergoes CO migratory insertion and reductive elimination to give the desired thioester product. PMID- 28989689 TI - Semisynthetic prion protein (PrP) variants carrying glycan mimics at position 181 and 197 do not form fibrils. AB - The prion protein (PrP) is an N-glycosylated protein attached to the outer leaflet of eukaryotic cell membranes via a glycosylphosphatidylinositol (GPI) anchor. Different prion strains have distinct glycosylation patterns and the extent of glycosylation of potentially pathogenic misfolded prion protein (PrPSc) has a major impact on several prion-related diseases (transmissible spongiform encephalopathies, TSEs). Based on these findings it is hypothesized that posttranslational modifications (PTMs) of PrP influence conversion of cellular prion protein (PrPC) into PrPSc and, as such, modified PrP variants are critical tools needed to investigate the impact of PTMs on the pathogenesis of TSEs. Here we report a semisynthetic approach to generate PrP variants modified with monodisperse polyethyleneglycol (PEG) units as mimics of N-glycans. Incorporating PEG at glycosylation sites 181 and 197 in PrP induced only small changes to the secondary structure when compared to unmodified, wildtype PrP. More importantly, in vitro aggregation was abrogated for all PEGylated PrP variants under conditions at which wildtype PrP aggregated. Furthermore, the addition of PEGylated PrP as low as 10 mol% to wildtype PrP completely blocked aggregation. A similar effect was observed for synthetic PEGylated PrP segments comprising amino acids 179-231 alone if these were added to wildtype PrP in aggregation assays. This behavior raises the question if large N-glycans interfere with aggregation in vivo and if PEGylated PrP peptides could serve as potential therapeutics. PMID- 28989692 TI - Nickel-catalyzed C-H/N-H annulation of aromatic amides with alkynes in the absence of a specific chelation system. AB - The Ni-catalyzed reaction of aromatic amides with alkynes in the presence of KOBu t involves C-H/N-H oxidative annulation to give 1(2H)-isoquinolinones. A key to the success of the reaction is the use of a catalytic amount of strong base, such as KOBu t . The reaction shows a high functional group compatibility. The reaction with unsymmetrical alkynes, such as 1-arylalkynes, gives the corresponding 1(2H)-isoquinolinones with a high level of regioselectivity. This discovery would lead to the development of Ni-catalyzed chelation-assisted C-H functionalization reactions without the need for a specific chelation system. PMID- 28989691 TI - Catalytic asymmetric hydroxylative dearomatization of 2-naphthols: synthesis of lacinilene derivatives. AB - An enantioselective hydroxylative dearomatization of 2-naphthols with oxaziridines has been accomplished using a N,N'-dioxide-scandium(iii) complex catalyst. Various substituted ortho-quinols could be obtained in high yields (up to 99%) and enantioselectivities (up to 95 : 5 er). This methodology could be applied in the synthesis of bioactive lacinilenes in a gram-scale reaction. Based on the experimental investigations and previous work, a possible catalytic model was proposed. PMID- 28989690 TI - Visible-light-induced oxidant and metal-free dehydrogenative cascade trifluoromethylation and oxidation of 1,6-enynes with water. AB - Generally, oxy-trifluoromethylation in olefins is achieved using oxidants and transition metal catalysts. However, labile olefins remain unexplored due to their incompatibility with harsh reaction conditions. Here, unprecedented light induced oxidant and metal-free tandem radical cyclization-trifluoromethylation and dehydrogenative oxygenation of 1,6-enynes have been achieved using a photoredox catalyst, CF3SO2Na, and phenanthrene-9,10-dione (PQ), Langlois' reagent (CF3SO2Na) and water as the oxygen source. This benign protocol allows for access to various CF3-containing C3-aryloyl/acylated benzofurans, benzothiophenes, and indoles. Moreover, the oxidized undesired products, which are inherently formed by the cleavage of the vinylic carbon and heteroatom bond, have been circumvented under oxidant free conditions. The mechanistic investigations by UV-visible and ESR spectroscopy, electrochemical studies, isotope labelling and density functional theory (DFT) suggest that light induced PQ produced a CF3 radical from CF3SO2Na. The generated CF3 radical adds to the alkene, followed by cyclization, to provide a vinylic radical that transfers an electron to PQ and generates a vinylic cation. Alternatively, electron transfer may occur from the CF3-added alkene moiety, forming a carbocation, which would undergo cationic cyclization to generate a vinylic carbocation. The subsequent addition of water to the vinylic cation, followed by the elimination of hydrogen gas, led to the formation of trifluoromethylated C3-aryloyl/acylated heterocycles. PMID- 28989693 TI - Asymmetric syntheses of 8-oxabicyclo[3,2,1]octane and 11 oxatricyclo[5.3.1.0]undecane from glycals. AB - Herein, we describe an efficient method to prepare enantiomerically pure 8 oxabicyclo[3.2.1]octanes via gold(i)-catalyzed tandem 1,3-acyloxy migration/Ferrier rearrangement of glycal derived 1,6-enyne bearing propargylic carboxylates. The resultant compounds could then undergo interrupted Nazarov cyclization to afford diastereomerically pure 11-oxatricyclo[5.3.1.0]undecanes. PMID- 28989694 TI - Rotational and steric effects in water dissociative chemisorption on Ni(111). AB - Powerful laser techniques have recently enabled quantum-state resolved molecular beam experiments for investigating gas-surface reactions, which have unveiled intriguing vibrational, rotational, and also steric effects. For reactions involving polyatomic molecules, e.g., the dissociative chemisorption of methane and water, the rotational and related steric effects are far less understood despite a large body of theoretical work having been able to reproduce the observed vibrational mode specificity and related bond selectivity semi quantitatively or even within chemical accuracy. Herein, we report a high dimensional quantum dynamics study of water dissociation on Ni(111) on a first principles potential energy surface, focusing on the reactivities of D2O in various rotational quantum states with different spatial orientations. Through an accurate quantum mechanical description of this asymmetric top, remarkable dependence of the reactivity on the orientation is observed. This dependence is site specific and rotational state specific. These single site rotational and steric effects are partially justified by a sudden model on the basis of the overlap between the rotational wavefunctions and the angular potential near the transition state, but rotational steering also plays a significant role which complicates the dynamics. Although site averaging weakens the influence of initial rotational excitations and leads to minor effects to the reactivity, steric effects are predicted to be observable if the water molecule is selectively excited and aligned by a linearly polarized laser. PMID- 28989695 TI - Simultaneous visualization of the subfemtomolar expression of microRNA and microRNA target gene using HILO microscopy. AB - The family of microRNAs (miRNAs) not only plays an important role in gene regulation but is also useful for the diagnosis of diseases. A reliable method with high sensitivity may allow researchers to detect slight fluctuations in ultra-trace amounts of miRNA. In this study, we propose a sensitive imaging method for the direct probing of miR-10b (miR-10b-3p, also called miR-10b*) and its target (HOXD10 mRNA) in fixed cells based on the specific recognition of molecular beacons combined with highly inclined and laminated optical sheet (HILO) fluorescence microscopy. The designed dye-quencher-labelled molecular beacons offer excellent efficiencies of fluorescence resonance energy transfer that allow us to detect miRNA and the target mRNA simultaneously in hepatocellular carcinoma cells using HILO fluorescence microscopy. Not only can the basal trace amount of miRNA be observed in each individual cell, but the obtained images also indicate that this method is useful for monitoring the fluctuations in ultra-trace amounts of miRNA when the cells are transfected with a miRNA precursor or a miRNA inhibitor (anti-miR). Furthermore, a reasonable causal relation between the miR-10b and HOXD10 expression levels was observed in miR-10b* precursor-transfected cells and miR-10b* inhibitor-transfected cells. The trends of the miRNA alterations obtained using HILO microscopy completely matched the RT-qPCR data and showed remarkable reproducibility (the coefficient of variation [CV] = 0.86%) and sensitivity (<1.0 fM). This proposed imaging method appears to be useful for the simultaneous visualisation of ultra-trace amounts of miRNA and target mRNA and excludes the procedures for RNA extraction and amplification. Therefore, the visualisation of miRNA and the target mRNA should facilitate the exploration of the functions of ultra-trace amounts of miRNA in fixed cells in biological studies and may serve as a powerful tool for diagnoses based on circulating cancer cells. PMID- 28989696 TI - Nitro-enabled catalytic enantioselective formal umpolung alkenylation of beta ketoesters. AB - A formal umpolung strategy is presented for the enantioselective installation of an alkenyl group with a terminal double bond at a tertiary center. This one-pot two-step sequence relies on the unique features of the nitro group, which after inverting the polarity of the alkenylating agent toward the desired bond formation, itself serves as a leaving group. The application of this protocol to cyclic beta-ketoesters results in densely functionalized products, bearing an all carbon quaternary stereocenter including an alkenyl substituent with a terminal double bond, in high yields with excellent enantioselectivities. PMID- 28989697 TI - Colors of the Sublunar. AB - Generic red, green, and blue images can be regarded as data sources of coarse (three bins) local spectra, typical data volumes are 104 to 107 spectra. Image data bases often yield hundreds or thousands of images, yielding data sources of 109 to 1010 spectra. There is usually no calibration, and there often are various nonlinear image transformations involved. However, we argue that sheer numbers make up for such ambiguity. We propose a model of spectral data mining that applies to the sublunar realm, spectra due to the scattering of daylight by objects from the generic terrestrial environment. The model involves colorimetry and ecological physics. Whereas the colorimetry is readily dealt with, one needs to handle the ecological physics with heuristic methods. The results suggest evolutionary causes of the human visual system. We also suggest effective methods to generate red, green, and blue color gamuts for various terrains. PMID- 28989699 TI - The status of transarterial chemoembolization treatment in the era of precision oncology. AB - Transarterial chemoembolization (TACE) is the gold standard of therapy for patients with unresectable intermediate stage hepatocellular carcinoma (HCC), and is also commonly used as postresection adjuvant therapy in Asia. The delivery of TACE is highly variable from center to center, and clinical decision making for patients is based primarily on tumor staging guidelines, with very little focus on individualized tumor features. This review will discuss recent efforts for improving patient outcomes with TACE treatment through personalized medicine advances, including ongoing clinical trials investigating the combination of targeted therapy with TACE and the discovery of prognostic biomarkers for predicting TACE response. PMID- 28989698 TI - Recent advances to accelerate re-endothelialization for vascular stents. AB - Cardiovascular diseases are considered as one of the serious diseases that leads to the death of millions of people all over the world. Stent implantation has been approved as an easy and promising way to treat cardiovascular diseases. However, in-stent restenosis and thrombosis remain serious problems after stent implantation. It was demonstrated in a large body of previously published literature that endothelium impairment represents a major factor for restenosis. This discovery became the driving force for many studies trying to achieve an optimized methodology for accelerated re-endothelialization to prevent restenosis. Thus, in this review, we summarize the different methodologies opted to achieve re-endothelialization, such as, but not limited to, manipulation of surface chemistry and surface topography. PMID- 28979764 TI - Saccharomyces cerevisiae show low levels of traversal across human endothelial barrier in vitro. AB - Background: Saccharomyces cerevisiae is generally considered safe, and is involved in the production of many types of foods and dietary supplements. However, some isolates, which are genetically related to strains used in brewing and baking, have shown virulent traits, being able to produce infections in humans, mainly in immunodeficient patients. This can lead to systemic infections in humans. Methods: In this work, we studied S. cerevisiae isolates in an in vitro human endothelial barrier model, comparing their behaviour with that of several strains of the related pathogens Candida glabrata and Candida albicans. Results: The results showed that this food related yeast is able to cross the endothelial barrier in vitro. However, in contrast to C. glabrata and C. albicans, S. cerevisiae showed very low levels of traversal. Conclusions: We conclude that using an in vitro human endothelial barrier model with S. cerevisiae can be useful to evaluate the safety of S. cerevisiae strains isolated from foods. PMID- 28989700 TI - Toxicological Implications of Mitochondrial Localization of CYP2E1. AB - Cytochrome P450 2E1 (CYP2E1) metabolizes an extensive array of pollutants, drugs, and other small molecules, often resulting in bioactivation to reactive metabolites. Therefore, it is unsurprising that it has been the subject of decades of research publications and reviews. However, while CYP2E1 has historically been studied in the endoplasmic reticulum (erCYP2E1), active CYP2E1 is also present in mitochondria (mtCYP2E1). Relatively few studies have specifically focused on mtCYP2E1, but there is growing interest in this form of the enzyme as a driver in toxicological mechanisms given its activity and location. Many previous studies have linked total CYP2E1 to conditions that involve mitochondrial dysfunction (fasting, diabetes, non-alcoholic steatohepatitis, and obesity). Furthermore, a large number of reactive metabolites that are formed by CYP2E1 through metabolism of drugs and pollutants have been demonstrated to cause mitochondrial dysfunction. Finally, there appears to be significant inter-individual variability in targeting to the mitochondria, which could constitute a source of variability in individual response to exposures. This review discusses those outcomes, the biochemical properties and toxicological consequences of mtCYP2E1, and highlights important knowledge gaps and future directions. Overall, we feel that this exciting area of research is rich with new and important questions about the relationship between mtCYP2E1, mitochondrial dysfunction, and pathology. PMID- 28989702 TI - Selective Adhesive Cell Capture without Molecular Specificity: New Surfaces Exploiting Nanoscopic Polycationic Features as Discrete Adhesive Units. AB - This work explored how molecularly non-specific polycationic nanoscale features on a collecting surface control kinetic and selectivity aspects of mammalian cell capture. Key principles for selective collector design were demonstrated by comparing the capture of two closely related breast cancer cell lines: MCF-7 and TMX2-28. TMX2-28 is a tamoxifen-selected clone of MCF-7. The collector was a silica surface, negatively-charged at pH 7.4, containing isolated molecules (~ 8 nm diameter) of the cationic polymer, poly(dimethyl-aminoethylmethacrylate), pDMAEMA. Important in this work is the non-selective nature of the pDMAEMA interactions with cells: pDMAEMA generally adheres negatively charged particles and cells in solution. We show here that selectivity towards cells results from collector design: this includes competition between repulsive interactions involving the negative silica and attractions to the immobilized pDMAEMA molecules, the random pDMAEMA arrangement on the surface, and the concentration of positive charge in the vicinity of the adsorbed pDMAEMA chains. The latter act as nanoscopic cationic surface patches, each weakly attracted to negatively charged cells. Collecting surfaces engineered with an appropriate amount pDMAEMA, exposed to mixtures of MCF-7 and TMX2-28 cells preferentially captured TMX2-28 with a selectivity of 2.5. (This means that the ratio of TMX2-28 to MCF cells on the surface was 2.5 times their compositional ratio in free solution.) The ionic strength-dependence of cell capture was shown to be similar to that of silica microparticles on the same surfaces. This suggests that the mechanism of selective cell capture involves nanoscopic differences in the contact areas of the cells with the collector, allowing discrimination of closely related cell line-based small scale features of the cell surface. This work demonstrated that even without molecular specificity, selectivity for physical cell attributes produces adhesive discrimination. PMID- 28989703 TI - An amphipathic trans-acting phosphorothioate RNA element delivers an uncharged phosphorodiamidate morpholino sequence in mdx mouse myotubes. AB - An efficient method for the delivery of uncharged polyA-tailed phosphorodiamidate morpholino sequences (PMO) in mammalian cells consists of employing a synthetic 8 mer amphipathic trans-acting poly-2'-O-methyluridylic thiophosphate triester element (2'-OMeUtaPS) as a transfection reagent. Unlike the dTtaPS DNA-based element, this RNA element is potent at delivering polyA-tailed PMO sequences to HeLa pLuc 705 cells or to myotube muscle cells. However, much like dTtaPS, the 2' OMeUtaPS-mediated internalization of PMO sequences occurs through an energy dependent mechanism; macropinocytosis appears to be the predominant endocytic pathway used for cellular uptake. The transfected PMO sequences induce alternate splicing of either the pre-mRNA encoding luciferase in HeLa pLuc 705 cells or the excision of exon 23 from the pre-mRNA encoding dystrophin in myotube muscle cells of the mdx mouse model of muscular dystrophy with an efficiency comparable to that of commercial cationic lipid reagents but without detrimental cytotoxicity. PMID- 28989704 TI - GENESIS - The GENEric SImulation System for Modelling State Transitions. AB - This software implements a discrete time Markov chain model, used to model transitions between states when the transition probabilities are known a priori. It is highly configurable; the user supplies two text files, a "state transition table" and a "config file", to the Perl script genesis.pl. Given the content of these files, the script generates a set of C++ classes based on the State design pattern, and a main program, which can then be compiled and run. The C++ code generated is based on the specification in the text files. Both multiple branching and bi-directional transitions are allowed. The software has been used to model the natural histories of colorectal cancer in Mexico. Although written primarily to model such disease processes, it can be used in any process which depends on discrete states with known transition probabilities between those states. One suitable area may be in environmental modelling. A test suite is supplied with the distribution. Due to its high degree of configurability and flexibility, this software has good re-use potential. It is stored on the Figshare repository. PMID- 28989705 TI - Collagen-mimetic hydrogels promote human endothelial cell adhesion, migration and phenotypic maturation. AB - This work evaluates the response of human aortic endothelial cells (HAECs) to thromboresistant collagen-mimetic hydrogel coatings toward improving the biocompatibility of existing "off-the-shelf" small-caliber vascular grafts. Specifically, bioactive hydrogels - previously shown to support alpha1/alpha2 integrin-mediated cell adhesion but to resist platelet activation - were fabricated by combining poly(ethylene glycol) (PEG) with a 120 kDa, triple helical collagen-mimetic protein(Scl2-2) containing the GFPGER adhesion sequence. Analysis of HAECs seeded onto the resulting PEG-Scl2-2 hydrogels demonstrated that HAEC adhesion increased with increasing Scl2-2 concentration, while HAEC migration rate decreased over this same concentration range. In addition, evaluation of HAEC phenotype at confluence indicated significant differences in the gene expression of NOS3, thrombomodulin, and E-selectin on the PEG-Scl2-2 hydrogels relative to PEG-collagen controls. At the protein level, however, only NOS3 was significantly different between the PEG-Scl2-2 and PEG-collagen surfaces. Furthermore, PECAM-1 and VE-cadherin expression on PEG-Scl2-2 hydrogels versus PEG-collagen controls could not be distinguished at either the gene or protein level. Cumulatively, these data indicate the PEG-Scl2-2 hydrogels warrant further investigation as "off-the-shelf" graft coatings. In future studies, the Scl2-2 protein can potentially be modified to include additional extracellular matrix or cytokine binding sites to further improve endothelial cell responses. PMID- 28989707 TI - What is the best way to determine bond-valence parameters? AB - Two recent systematic determinations of bond-valence parameters addressed the problem of the correlation between R0 and b in different ways raising the question of which is to be preferred. PMID- 28989706 TI - Standard 12 month dialectical behaviour therapy for adults with borderline personality disorder in a public community mental health setting. AB - BACKGROUND: Dialectical behaviour therapy (DBT) is noted to be an intervention with a growing body of evidence that demonstrates its efficacy in treating individuals diagnosed with borderline personality disorder (BPD). Evidence for the effectiveness of DBT in publicly funded community mental health settings is lacking however. No study to our knowledge has been published on the effectiveness of a 12 month standard DBT programme without adaptations for individuals with BPD in a publicly funded community mental health setting and no study has included data across multiple time-points. The main objective of the current study was to determine if completion of a 12 month DBT programme is associated with improved outcomes in terms of borderline symptoms, anxiety, hopelessness, suicidal ideation, depression and quality of life. A secondary objective includes assessing client progress across multiple time-points throughout the treatment. METHODS: Fifty-four adult participants with BPD completed the standard DBT programme across four sites in community mental health settings in the Republic of Ireland. Data was collected by the DBT therapists working with participants and took place at 8 week intervals across the 12 month programme. To explore the effects of the intervention for participants, linear mixed-effects models were used to estimate change utilising data available from all time-points. RESULTS: At the end of the 12 month programme, significant reductions in borderline symptoms, anxiety, hopelessness, suicidal ideation and depression were observed. Increases in overall quality of life were also noted. In particular, gains were made during the first 6 months of the programme. There was a tendency for scores to slightly regress after the six-month mark which marks the start of the second delivery of the group skills cycles. CONCLUSIONS: The current study provides evidence for the effectiveness of standard DBT in publicly funded community mental health settings. As participants were assessed at the end of every module, it was possible to observe trends in symptom reduction during each stage of the intervention. Despite real-world limitations of applying DBT in community settings, the results of this study are comparable with more tightly controlled studies. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03166579; Registered May 24th 2017 'retrospectively registered'. PMID- 28989708 TI - Experimental phasing of serial femtosecond crystallography data. AB - A synopsis of and prospects for de novo phasing using diffraction data collected at X-ray free-electron lasers are given. PMID- 28989709 TI - Progress in small-angle scattering from biological solutions at high-brilliance synchrotrons. AB - Small-angle X-ray scattering (SAXS) is an established technique that provides low resolution structural information on macromolecular solutions. Recent decades have witnessed significant progress in both experimental facilities and in novel data-analysis approaches, making SAXS a mainstream method for structural biology. The technique is routinely applied to directly reconstruct low-resolution shapes of proteins and to generate atomistic models of macromolecular assemblies using hybrid approaches. Very importantly, SAXS is capable of yielding structural information on systems with size and conformational polydispersity, including highly flexible objects. In addition, utilizing high-flux synchrotron facilities, time-resolved SAXS allows analysis of kinetic processes over time ranges from microseconds to hours. Dedicated bioSAXS beamlines now offer fully automated data collection and analysis pipelines, where analysis and modelling is conducted on the fly. This enables SAXS to be employed as a high-throughput method to rapidly screen various sample conditions and additives. The growing SAXS user community is supported by developments in data and model archiving and quality criteria. This review illustrates the latest developments in SAXS, in particular highlighting time-resolved applications aimed at flexible and evolving systems. PMID- 28989710 TI - Protein microcrystallography using synchrotron radiation. AB - The progress in X-ray microbeam applications using synchrotron radiation is beneficial to structure determination from macromolecular microcrystals such as small in meso crystals. However, the high intensity of microbeams causes severe radiation damage, which worsens both the statistical quality of diffraction data and their resolution, and in the worst cases results in the failure of structure determination. Even in the event of successful structure determination, site specific damage can lead to the misinterpretation of structural features. In order to overcome this issue, technological developments in sample handling and delivery, data-collection strategy and data processing have been made. For a few crystals with dimensions of the order of 10 um, an elegant two-step scanning strategy works well. For smaller samples, the development of a novel method to analyze multiple isomorphous microcrystals was motivated by the success of serial femtosecond crystallography with X-ray free-electron lasers. This method overcame the radiation-dose limit in diffraction data collection by using a sufficient number of crystals. Here, important technologies and the future prospects for microcrystallography are discussed. PMID- 28989711 TI - Real-time powder diffraction studies of energy materials under non-equilibrium conditions. AB - Energy materials form the central part of energy devices. An essential part of their function is the ability to reversibly host charge or energy carriers, and analysis of their phase composition and structure in real time under non equilibrium conditions is mandatory for a full understanding of their atomic scale functional mechanism. Real-time powder diffraction is increasingly being applied for this purpose, forming a critical step in the strategic chemical engineering of materials with improved behaviour. This topical review gives examples of real-time analysis using powder diffraction of rechargeable battery electrodes and porous sorbent materials used for the separation and storage of energy-relevant gases to demonstrate advances in the insights which can be gained into their atomic-scale function. PMID- 28989712 TI - Pair distribution functions of amorphous organic thin films from synchrotron X ray scattering in transmission mode. AB - Using high-brilliance high-energy synchrotron X-ray radiation, for the first time the total scattering of a thin organic glass film deposited on a strongly scattering inorganic substrate has been measured in transmission mode. The organic thin film was composed of the weakly scattering pharmaceutical substance indomethacin in the amorphous state. The film was 130 um thick atop a borosilicate glass substrate of equal thickness. The atomic pair distribution function derived from the thin-film measurement is in excellent agreement with that from bulk measurements. This ability to measure the total scattering of amorphous organic thin films in transmission will enable accurate in situ structural studies for a wide range of materials. PMID- 28989714 TI - zeta-Glycine: insight into the mechanism of a polymorphic phase transition. AB - Glycine is the simplest and most polymorphic amino acid, with five phases having been structurally characterized at atmospheric or high pressure. A sixth form, the elusive zeta phase, was discovered over a decade ago as a short-lived intermediate which formed as the high-pressure ? phase transformed to the gamma form on decompression. However, its structure has remained unsolved. We now report the structure of the zeta phase, which was trapped at 100 K enabling neutron powder diffraction data to be obtained. The structure was solved using the results of a crystal structure prediction procedure based on fully ab initio energy calculations combined with a genetic algorithm for searching phase space. We show that the fate of zeta-glycine depends on its thermal history: although at room temperature it transforms back to the gamma phase, warming the sample from 100 K to room temperature yielded beta-glycine, the least stable of the known ambient-pressure polymorphs. PMID- 28989713 TI - Start-to-end simulation of single-particle imaging using ultra-short pulses at the European X-ray Free-Electron Laser. AB - Single-particle imaging with X-ray free-electron lasers (XFELs) has the potential to provide structural information at atomic resolution for non-crystalline biomolecules. This potential exists because ultra-short intense pulses can produce interpretable diffraction data notwithstanding radiation damage. This paper explores the impact of pulse duration on the interpretability of diffraction data using comprehensive and realistic simulations of an imaging experiment at the European X-ray Free-Electron Laser. It is found that the optimal pulse duration for molecules with a few thousand atoms at 5 keV lies between 3 and 9 fs. PMID- 28989716 TI - Coherent amplification of X-ray scattering from meso-structures. AB - Small-angle X-ray scattering (SAXS) often includes an unwanted background, which increases the required measurement time to resolve the sample structure. This is undesirable in all experiments, and may make measurement of dynamic or radiation sensitive samples impossible. Here, we demonstrate a new technique, applicable when the scattering signal is background-dominated, which reduces the requisite exposure time. Our method consists of exploiting coherent interference between a sample with a designed strongly scattering 'amplifier'. A modified angular correlation function is used to extract the symmetry of the interference term; that is, the scattering arising from the interference between the amplifier and the sample. This enables reconstruction of the sample's symmetry, despite the sample scattering itself being well below the intensity of background scattering. Thus, coherent amplification is used to generate a strong scattering term (well above background), from which sample scattering is inferred. We validate this method using lithographically defined test samples. PMID- 28989715 TI - Spin-reorientation magnetic transitions in Mn-doped SmFeO3. AB - Spin reorientation is a magnetic phase transition in which rotation of the magnetization vector with respect to the crystallographic axes occurs upon a change in the temperature or magnetic field. For example, SmFeO3 shows a magnetization rotation from the c axis above 480 K to the a axis below 450 K, known as the Gamma4 -> Gamma2 transition. This work reports the successful synthesis of the new single-crystal perovskite SmFe0.75Mn0.25O3 and finds interesting spin reorientations above and below room temperature. In addition to the spin reorientation of the Gamma4 -> Gamma2 magnetic phase transition observed at around TSR2 = 382 K, a new spin reorientation, Gamma2 -> Gamma1, was seen at around TSR1 = 212 K due to Mn doping, which could not be observed in the parent rare earth perovskite compound. This unexpected spin configuration has complete antiferromagnetic order without any canting-induced weak ferromagnetic moment, resulting in zero magnetization in the low-temperature regime. M-T and M-H measurements have been made to study the temperature and magnetic-field dependence of the observed spin reorientation transitions. PMID- 28989717 TI - Bond softness sensitive bond-valence parameters for crystal structure plausibility tests. AB - Based on a description of bond valence as a function of valence electron density, a systematic bond softness sensitive approach to determine bond-valence parameters and related quantities such as coordination numbers is elaborated and applied to determine bond-valence parameters for 706 cation-anion pairs. While the approach is closely related to the earlier softBV parameter set, the new softNC1 parameters proposed in this work may be simpler to apply in plausibility checks of crystal structures, as they follow the first coordination shell convention. The performance of this softNC1 bond-valence parameter set is compared with that of the previously derived softBV parameter set that also factors in contributions from higher coordination shells, and with a benchmarking parameter set that has been optimized following the conventional choice of a universal value of the bond-valence parameter b. The results show that a systematic adaptation of the bond-valence parameters to the bond softness leads to a significant improvement in the bond-valence parameters, particularly for bonds involving soft anions, and is safer than individual free refinements of both R0 and b from a limited number of reference cation environments. PMID- 28989718 TI - Background modelling of diffraction data in the presence of ice rings. AB - An algorithm for modelling the background for each Bragg reflection in a series of X-ray diffraction images containing Debye-Scherrer diffraction from ice in the sample is presented. The method involves the use of a global background model which is generated from the complete X-ray diffraction data set. Fitting of this model to the background pixels is then performed for each reflection independently. The algorithm uses a static background model that does not vary over the course of the scan. The greatest improvement can be expected for data where ice rings are present throughout the data set and the local background shape at the size of a spot on the detector does not exhibit large time-dependent variation. However, the algorithm has been applied to data sets whose background showed large pixel variations (variance/mean > 2) and has been shown to improve the results of processing for these data sets. It is shown that the use of a simple flat-background model as in traditional integration programs causes systematic bias in the background determination at ice-ring resolutions, resulting in an overestimation of reflection intensities at the peaks of the ice rings and an underestimation of reflection intensities either side of the ice ring. The new global background-model algorithm presented here corrects for this bias, resulting in a noticeable improvement in R factors following refinement. PMID- 28989720 TI - One enzyme, many reactions: structural basis for the various reactions catalyzed by naphthalene 1,2-dioxygenase. AB - Rieske nonheme iron oxygenases (ROs) are a well studied class of enzymes. Naphthalene 1,2-dioxygenase (NDO) is used as a model to study ROs. Previous work has shown how side-on binding of oxygen to the mononuclear iron provides this enzyme with the ability to catalyze stereospecific and regiospecific cis dihydroxylation reactions. It has been well documented that ROs catalyze a variety of other reactions, including mono-oxygenation, desaturation, O- and N dealkylation, sulfoxidation etc. NDO itself catalyzes a variety of these reactions. Structures of NDO in complex with a number of different substrates show that the orientation of the substrate in the active site controls not only the regiospecificity and stereospecificity, but also the type of reaction catalyzed. It is proposed that the mononuclear iron-activated dioxygen attacks the atoms of the substrate that are most proximal to it. The promiscuity of delivering two products (apparently by two different reactions) from the same substrate can be explained by the possible binding of the substrate in slightly different orientations aided by the observed flexibility of residues in the binding pocket. PMID- 28989719 TI - Experimental phase determination with selenomethionine or mercury-derivatization in serial femtosecond crystallography. AB - Serial femtosecond crystallography (SFX) using X-ray free-electron lasers (XFELs) holds enormous potential for the structure determination of proteins for which it is difficult to produce large and high-quality crystals. SFX has been applied to various systems, but rarely to proteins that have previously unknown structures. Consequently, the majority of previously obtained SFX structures have been solved by the molecular replacement method. To facilitate protein structure determination by SFX, it is essential to establish phasing methods that work efficiently for SFX. Here, selenomethionine derivatization and mercury soaking have been investigated for SFX experiments using the high-energy XFEL at the SPring-8 Angstrom Compact Free-Electron Laser (SACLA), Hyogo, Japan. Three successful cases are reported of single-wavelength anomalous diffraction (SAD) phasing using X-rays of less than 1 A wavelength with reasonable numbers of diffraction patterns (13 000, 60 000 and 11 000). It is demonstrated that the combination of high-energy X-rays from an XFEL and commonly used heavy-atom incorporation techniques will enable routine de novo structural determination of biomacromolecules. PMID- 28989721 TI - A distance geometry-based description and validation of protein main-chain conformation. AB - Understanding the protein main-chain conformational space forms the basis for the modelling of protein structures and for the validation of models derived from structural biology techniques. Presented here is a novel idea for a three dimensional distance geometry-based metric to account for the fine details of protein backbone conformations. The metrics are computed for dipeptide units, defined as blocks of Calphai-1-O i-1-Calphai -O i -Calphai+1 atoms, by obtaining the eigenvalues of their Euclidean distance matrices. These were computed for ~1.3 million dipeptide units collected from nonredundant good-quality structures in the Protein Data Bank and subjected to principal component analysis. The resulting new Euclidean orthogonal three-dimensional space (DipSpace) allows a probabilistic description of protein backbone geometry. The three axes of the DipSpace describe the local extension of the dipeptide unit structure, its twist and its bend. By using a higher-dimensional metric, the method is efficient for the identification of Calpha atoms in an unlikely or unusual geometrical environment, and its use for both local and overall validation of protein models is demonstrated. It is also shown, for the example of trypsin proteases, that the detection of unusual conformations that are conserved among the structures of this protein family may indicate geometrically strained residues of potentially functional importance. PMID- 28989722 TI - A closer look into close packing: pentacoordinated silicon in a high-pressure polymorph of danburite. AB - Due to their high technological and geological relevance, silicates are one of the most studied classes of inorganic compounds. Under ambient conditions, the silicon in silicates is almost exclusively coordinated by four oxygen atoms, while high-pressure treatment normally results in an increase in the coordination from four- to sixfold. Reported here is a high-pressure single-crystal X-ray diffraction study of danburite, CaB2Si2O8, the first compound showing a step-wise transition of Si coordination from tetrahedral to octahedral through a trigonal bipyramid. Along the compression, the Si2O7 groups of danburite first transform into chains of vertice-sharing SiO5 trigonal bipyramids (danburite-II) and later into chains of edge-sharing SiO6 octahedra (danburite-III). It is suggested that the unusual formation of an SiO5 configuration is a consequence of filling up the pentacoordinated voids in the distorted hexagonal close packing of danburite-II. PMID- 28989725 TI - Crystallographic features of the martensitic transformation and their impact on variant organization in the intermetallic compound Ni50Mn38Sb12 studied by SEM/EBSD. AB - The mechanical and magnetic properties of Ni-Mn-Sb intermetallic compounds are closely related to the martensitic transformation and martensite variant organization. However, studies of these issues are very limited. Thus, a thorough crystallographic investigation of the martensitic transformation orientation relationship (OR), the transformation deformation and their impact on the variant organization of an Ni50Mn38Sb12 alloy using scanning electron microscopy/electron backscatter diffraction (SEM/EBSD) was conducted in this work. It is shown that the martensite variants are hierarchically organized into plates, each possessing four distinct twin-related variants, and the plates into plate colonies, each containing four distinct plates delimited by compatible and incompatible plate interfaces. Such a characteristic organization is produced by the martensitic transformation. It is revealed that the transformation obeys the Pitsch relation ({0[Formula: see text]}A // {2[Formula: see text]}M and <0[Formula: see text]1>A // <[Formula: see text]2>M; the subscripts A and M refer to austenite and martensite, respectively). The type I twinning plane K1 of the intra-plate variants and the compatible plate interface plane correspond to the respective orientation relationship planes {0[Formula: see text]}A and {0[Formula: see text]}A of austenite. The three {0[Formula: see text]}A planes possessed by each pair of compatible plates, one corresponding to the compatible plate interface and the other two to the variants in the two plates, are interrelated by 60 degrees and belong to a single <11[Formula: see text]>A axis zone. The {0[Formula: see text]}A planes representing the two pairs of compatible plates in each plate colony belong to two <11[Formula: see text]>A axis zones having one {0[Formula: see text]}A plane in common. This common plane defines the compatible plate interfaces of the two pairs of plates. The transformation strains to form the variants in the compatible plates are compatible and demonstrate an edge-to edge character. Thus, such plates should nucleate and grow simultaneously. On the other hand, the strains to form the variants in the incompatible plates are incompatible, so they nucleate and grow separately until they meet during the transformation. The results of the present work provide comprehensive information on the martensitic transformation of Ni-Mn-Sb intermetallic compounds and its impact on martensite variant organization. PMID- 28989724 TI - Charge-transport properties of 4-(1,2,2-tri-phenyl-vinyl)-aniline salicylaldehyde hydrazone: tight-packing induced molecular 'hardening'. AB - Based on first-principles calculations, the relationship between molecular packing and charge-transport parameters has been investigated and analysed in detail. It is found that the crystal packing forces in the flexible organic molecule 4-(1,2,2-triphenylvinyl)-aniline salicylaldehyde hydrazone (A) can apparently overcome the dynamic intramolecular rotations and the intramolecular steric repulsion, effectively enhancing the molecular rigidity and decreasing the internal reorganization energy. The conducting properties of A have also been simulated within the framework of hopping models, and the calculation results show that the intrinsic electron mobility in A is much higher than the corresponding intrinsic hole mobility. These theoretical investigations provide guidance for the efficient and targeted control of the molecular packing and charge-transport properties of organic small-molecule semiconductors and conjugated polymeric materials. PMID- 28989723 TI - Single-particle cryo-EM using alignment by classification (ABC): the structure of Lumbricus terrestris haemoglobin. AB - Single-particle cryogenic electron microscopy (cryo-EM) can now yield near-atomic resolution structures of biological complexes. However, the reference-based alignment algorithms commonly used in cryo-EM suffer from reference bias, limiting their applicability (also known as the 'Einstein from random noise' problem). Low-dose cryo-EM therefore requires robust and objective approaches to reveal the structural information contained in the extremely noisy data, especially when dealing with small structures. A reference-free pipeline is presented for obtaining near-atomic resolution three-dimensional reconstructions from heterogeneous ('four-dimensional') cryo-EM data sets. The methodologies integrated in this pipeline include a posteriori camera correction, movie-based full-data-set contrast transfer function determination, movie-alignment algorithms, (Fourier-space) multivariate statistical data compression and unsupervised classification, 'random-startup' three-dimensional reconstructions, four-dimensional structural refinements and Fourier shell correlation criteria for evaluating anisotropic resolution. The procedures exclusively use information emerging from the data set itself, without external 'starting models'. Euler angle assignments are performed by angular reconstitution rather than by the inherently slower projection-matching approaches. The comprehensive 'ABC-4D' pipeline is based on the two-dimensional reference-free 'alignment by classification' (ABC) approach, where similar images in similar orientations are grouped by unsupervised classification. Some fundamental differences between X ray crystallography versus single-particle cryo-EM data collection and data processing are discussed. The structure of the giant haemoglobin from Lumbricus terrestris at a global resolution of ~3.8 A is presented as an example of the use of the ABC-4D procedure. PMID- 28989726 TI - Carbohydrate-last meal pattern lowers postprandial glucose and insulin excursions in type 2 diabetes. AB - BACKGROUND: There are limited data regarding the timing of carbohydrate ingestion during a meal and postprandial glucose regulation. METHODS: Sixteen subjects with type 2 diabetes mellitus (T2DM) consumed the same meal on 3 days in random order: carbohydrate first, followed 10 min later by protein and vegetables; protein and vegetables first, followed 10 min later by carbohydrate; or all components together. Blood was sampled for glucose, insulin, glucagon-like peptide-1 (GLP 1), and glucagon measurements at baseline (just before meal ingestion) and subsequently at 30 min intervals up to 180 min. RESULTS: The incremental areas under the curve for glucose (iAUC0-180) and incremental glucose peaks were 53% and 54% lower, respectively, when carbohydrate was consumed last compared with carbohydrate consumed first (3124.7+/-501.2 vs 6703.5+/-904.6 mg/dL*180min, p<0.001; 34.7+/-4.1 vs 75.0+/-6.5 mg/dL, p<0.001) and 44% and 40% lower, respectively, compared with the all components together condition (3124.7+/-501.2 vs 5587.1+/-828.7 mg/dL*180min, p=0.003; 34.7+/-4.1 vs 58.2+/-5.9 mg/dL, p<0.001). Postprandial insulin excursions were lower (iAUC0-180: 7354.1+/-897.3 vs 9769.7+/-1002.1 uU/mL*min, p=0.003) and GLP-1 excursions higher (iAUC0-180: 3487.56+/-327.7 vs 2519.11+/-494.8 pg/mL*min, p=0.019) following the carbohydrate last meal order compared with carbohydrate first. CONCLUSION: The carbohydrate last meal pattern may be an effective behavioral strategy to improve postprandial glycemia. PMID- 28989727 TI - Preparation in the business and practice of medicine: perspectives from recent gynecologic oncology graduates and program directors. AB - BACKGROUND: Preparation in the business of medicine is reported to be poor across a number of specialties. No data exist about such preparation in gynecologic oncology training programs. Our objectives were to evaluate current time dedicated to these initiatives, report recent graduate perceptions about personal preparedness, and assess areas where improvements in training can occur. METHODS: Two separate surveys were created and distributed, one to 183 Society of Gynecologic Oncology candidate members and the other to 48 gynecologic oncology fellowship program directors. Candidate member surveys included questions about perceived preparedness for independent research, teaching, job-hunting, insurance, and billing. Program director surveys assessed current and desired time dedicated to the topics asked concurrently on the candidate survey. Statistical analysis was performed using Chi-squared (or Fisher's exact test if appropriate) and logistic regression. RESULTS: Survey response rates of candidate members and program directors were 28% and 40%, respectively. Candidate members wanted increased training in all measures except retrospective protocol writing. Female candidates wanted more training on writing letters of intent (LOI) (p = 0.01) and billing (p < 0.01). Compared to their current schedules, program directors desired more time to teach how to write an investigator initiated trial (p = 0.01). 94% of program directors reported having career goal discussions with their fellows, while only 72% of candidate members reported that this occurred (p = 0.05). CONCLUSION: Recent graduates want more preparation in the non-clinical aspects of their careers. Reconciling program director and fellow desires and increasing communication between the two may serve to achieve the educational goals of each. PMID- 28989728 TI - Walking with wider steps changes foot placement control, increases kinematic variability and does not improve linear stability. AB - Walking humans respond to pulls or pushes on their upper body by changing where they place their foot on the next step. Usually, they place their foot further along the direction of the upper body perturbation. Here, we examine how this foot placement response is affected by the average step width during walking. We performed experiments with humans walking on a treadmill, both normally and at five different prescribed step widths. We prescribed step widths by requiring subjects to step on lines drawn on the treadmill belt. We inferred a linear model between the torso marker state at mid-stance and the next foot position. The coefficients in this linear model (which are analogous to feedback gains for foot placement) changed with increasing step width as follows. The sideways foot placement response to a given sideways torso deviation decreased. The fore-aft foot placement response to a given fore-aft torso deviation also decreased. Coupling between fore-aft foot placement and sideways torso deviations increased. These changes in foot placement feedback gains did not significantly affect walking stability as quantified by Floquet multipliers (which estimate how quickly the system corrects a small perturbation), despite increasing foot placement variance and upper body motion variance (kinematic variability). PMID- 28989729 TI - Adaptive recursive algorithm for optimal weighted suprathreshold stochastic resonance. AB - Suprathreshold stochastic resonance (SSR) is a distinct form of stochastic resonance, which occurs in multilevel parallel threshold arrays with no requirements on signal strength. In the generic SSR model, an optimal weighted decoding scheme shows its superiority in minimizing the mean square error (MSE). In this study, we extend the proposed optimal weighted decoding scheme to more general input characteristics by combining a Kalman filter and a least mean square (LMS) recursive algorithm, wherein the weighted coefficients can be adaptively adjusted so as to minimize the MSE without complete knowledge of input statistics. We demonstrate that the optimal weighted decoding scheme based on the Kalman-LMS recursive algorithm is able to robustly decode the outputs from the system in which SSR is observed, even for complex situations where the signal and noise vary over time. PMID- 28989730 TI - Subliminal influence on preferences? A test of evaluative conditioning for brief visual conditioned stimuli using auditory unconditioned stimuli. AB - In the field of evaluative conditioning (EC), two opposing theories-propositional single-process theory versus dual-process theory-are currently being discussed in the literature. The present set of experiments test a crucial prediction to adjudicate between these two theories: Dual-process theory postulates that evaluative conditioning can occur without awareness of the contingency between conditioned stimulus (CS) and unconditioned stimulus (US); in contrast, single process propositional theory postulates that EC requires CS-US contingency awareness. In a set of three studies, we experimentally manipulate contingency awareness by presenting the CSs very briefly, thereby rendering it unlikely to be processed consciously. We address potential issues with previous studies on EC with subliminal or near-threshold CSs that limited their interpretation. Across two experiments, we consistently found an EC effect for CSs presented for 1000 ms and consistently failed to find an EC effect for briefly presented CSs. In a third pre-registered experiment, we again found evidence for an EC effect with CSs presented for 1000 ms, and we found some indication for an EC effect for CSs presented for 20 ms. PMID- 28989731 TI - Learning of efficient behaviour in spatial exploration through observation of behaviour of conspecific in laboratory rats. AB - Recent studies have suggested that rodent behaviour is influenced by the behaviour of surrounding conspecifics (e.g. emotional contagion and prosocial behaviour). However, little is known about deferred imitation and complex observational learning in rats. The purpose of this study was to reveal whether rats can learn from another rat's experiences. In a maze, observer rats watched the foraging behaviour of other rats (demonstrators) and then foraged in turn. The results showed that demonstrators explored inefficiently, but observers explored more efficiently after observing inefficient exploration by the demonstrators. This observational learning probably involved the acquisition of an efficient strategy through spatial exploration. PMID- 28989733 TI - The shrimp superfamily Sergestoidea: a global phylogeny with definition of new families and an assessment of the pathways into principal biotopes. AB - The phylogenetic analysis of Sergestoidea based on 253 morphological characters and encompassing all 99 valid species confirmed all previously recognized genus level clades. Analysis retrieved five major robust clades that correspond to families Luciferidae, Sergestidae, Acetidae fam.n., Sicyonellidae fam.n. and Petalidiumidae fam.n. Synonymy, emended diagnoses and composition of revealed family-level clades are provided. Three types of morphological characters were important in the phylogeny of the Sergestoidea: general external characters, copulatory organs, and photophores. Novel metrics to quantify the contribution of these character types were tested. General external characters were significant in supporting the major clades (80% of the families and nearly half of the genera). Copulatory organ characters and photophores greatly supported the medium level clades: Lucifer, Belzebub, Petalidium, Neosergestes, Challengerosergia (copulatory organ characters) and Lucensosergia, Challengerosergia, Gardinerosergia, Phorcosergia (photophores). An evolutionary model of the Sergestoidea showing their pathways into their principal biotopes is proposed: the major clades evolved in a vertical direction (from epi- to bathypelagic); further divergence at the genus level occurred within vertical zones in a horizontal direction, with the invasion of the benthopelagic and neritic (shelf and estuarine) habitats and speciation within these domains. PMID- 28989732 TI - Investigating the association between social interactions and personality states dynamics. AB - The recent personality psychology literature has coined the name of personality states to refer to states having the same behavioural, affective and cognitive content (described by adjectives) as the corresponding trait, but for a shorter duration. The variability in personality states may be the reaction to specific characteristics of situations. The aim of our study is to investigate whether specific situational factors, that is, different configurations of face-to-face interactions, are predictors of variability of personality states in a work environment. The obtained results provide evidence that within-person variability in personality is associated with variation in face-to-face interactions. Interestingly, the effects differ by type and level of the personality states: adaptation effects for Agreeableness and Emotional Stability, whereby the personality states of an individual trigger similar states in other people interacting with them and complementarity effects for Openness to Experience, whereby the personality states of an individual trigger opposite states in other people interacting with them. Overall, these findings encourage further research to characterize face-to-face and social interactions in terms of their relevance to personality states. PMID- 28989734 TI - Detecting rare asymmetrically methylated cytosines and decoding methylation patterns in the honeybee genome. AB - Context-dependent gene expression in eukaryotes is controlled by several mechanisms including cytosine methylation that primarily occurs in the CG dinucleotides (CpGs). However, less frequent non-CpG asymmetric methylation has been found in various cell types, such as mammalian neurons, and recent results suggest that these sites can repress transcription independently of CpG contexts. In addition, an emerging view is that CpG hemimethylation may arise not only from deregulation of cellular processes but also be a standard feature of the methylome. Here, we have applied a novel approach to examine whether asymmetric CpG methylation is present in a sparsely methylated genome of the honeybee, a social insect with a high level of epigenetically driven phenotypic plasticity. By combining strand-specific ultra-deep amplicon sequencing of illustrator genes with whole-genome methylomics and bioinformatics, we show that rare asymmetrically methylated CpGs can be unambiguously detected in the honeybee genome. Additionally, we confirm differential methylation between two phenotypically and reproductively distinct castes, queens and workers, and offer new insight into the heterogeneity of brain methylation patterns. In particular, we challenge the assumption that symmetrical methylation levels reflect symmetry in the underlying methylation patterns and conclude that hemimethylation may occur more frequently than indicated by methylation levels. Finally, we question the validity of a prior study in which most of cytosine methylation in this species was reported to be asymmetric. PMID- 28989735 TI - Perception of global image contrast involves transparent spatial filtering and the integration and suppression of local contrasts (not RMS contrast). AB - When adjusting the contrast setting on a television set, we experience a perceptual change in the global image contrast. But how is that statistic computed? We addressed this using a contrast-matching task for checkerboard configurations of micro-patterns in which the contrasts and spatial spreads of two interdigitated components were controlled independently. When the patterns differed greatly in contrast, the higher contrast determined the perceived global contrast. Crucially, however, low contrast additions of one pattern to intermediate contrasts of the other caused a paradoxical reduction in the perceived global contrast. None of the following metrics/models predicted this: max, linear sum, average, energy, root mean squared (RMS), Legge and Foley. However, a nonlinear gain control model, derived from contrast detection and discrimination experiments, incorporating wide-field summation and suppression, did predict the results with no free parameters, but only when spatial filtering was removed. We conclude that our model describes fundamental processes in human contrast vision (the pattern of results was the same for expert and naive observers), but that above threshold-when contrast pedestals are clearly visible vision's spatial filtering characteristics become transparent, tending towards those of a delta function prior to spatial summation. The global contrast statistic from our model is as easily derived as the RMS contrast of an image, and since it more closely relates to human perception, we suggest it be used as an image contrast metric in practical applications. PMID- 28989736 TI - Quantifying the dynamic wing morphing of hovering hummingbird. AB - Animal wings are lightweight and flexible; hence, during flapping flight their shapes change. It has been known that such dynamic wing morphing reduces aerodynamic cost in insects, but the consequences in vertebrate flyers, particularly birds, are not well understood. We have developed a method to reconstruct a three-dimensional wing model of a bird from the wing outline and the feather shafts (rachides). The morphological and kinematic parameters can be obtained using the wing model, and the numerical or mechanical simulations may also be carried out. To test the effectiveness of the method, we recorded the hovering flight of a hummingbird (Amazilia amazilia) using high-speed cameras and reconstructed the right wing. The wing shape varied substantially within a stroke cycle. Specifically, the maximum and minimum wing areas differed by 18%, presumably due to feather sliding; the wing was bent near the wrist joint, towards the upward direction and opposite to the stroke direction; positive upward camber and the 'washout' twist (monotonic decrease in the angle of incidence from the proximal to distal wing) were observed during both half strokes; the spanwise distribution of the twist was uniform during downstroke, but an abrupt increase near the wrist joint was found during upstroke. PMID- 28989737 TI - Familiarity affects collective motion in shoals of guppies (Poecilia reticulata). AB - The coordinated and synchronized movement of animals in groups often referred to as collective motion emerges through the interactions between individual animals within the group. Factors which affect these interactions have the potential to shape collective movement. One such factor is familiarity, or the tendency to bias behaviour towards individuals as a result of social recognition. We examined the effect of familiarity on the expression of collective motion in small shoals of female guppies (Poecilia reticulata). Groups comprising familiar individuals were more strongly polarized than groups of unfamiliar individuals, particularly when in novel surroundings. The ability to form more strongly polarized shoals potentially promotes information transfer and enhances the anti-predator benefits of grouping. PMID- 28989738 TI - Pragmatic analysis of the electric submerged arc furnace continuum. AB - A transient mathematical model was developed for the description of fluid flow, heat transfer and electromagnetic phenomena involved in the production of ferronickel in electric arc furnaces. The key operating variables considered were the thermal and electrical conductivity of the slag and the shape, immersion depth and applied electric potential of the electrodes. It was established that the principal stimuli of the velocities in the slag bath were the electric potential and immersion depth of the electrodes and the thermal and electrical conductivities of the slag. Additionally, it was determined that, under the set of operating conditions examined, the maximum slag temperature ranged between 1756 and 1825 K, which is in accordance with industrial measurements. Moreover, it was affirmed that contributions to slag stirring due to Lorentz forces and momentum forces due to the release of carbon monoxide bubbles from the electrode surface were negligible. PMID- 28989739 TI - Prey selection and dietary flexibility of three species of mammalian predator during an irruption of non-cyclic prey. AB - Predators often display dietary shifts in response to fluctuating prey in cyclic systems, but little is known about predator diets in systems that experience non cyclic prey irruptions. We tracked dietary shifts by feral cats (Felis catus), red foxes (Vulpes vulpes) and dingoes (Canis dingo) through a non-cyclic irruption of small mammalian prey in the Simpson Desert, central Australia. We predicted that all three predators would alter their diets to varying degrees as small mammals declined post irruption, and to test our predictions we live trapped small mammals through the irruption event and collected scats to track predator diets. Red foxes and dingoes included a broader variety of prey in their diets as small mammals declined. Feral cats did not exhibit a similar dietary shift, but did show variable use and selectivity of small mammal species through the irruption cycle. Results were largely consistent with prior studies that highlighted the opportunistic feeding habits of the red fox and dingo. They also, however, showed that feral cats may exhibit less dietary flexibility in response to small mammal irruptions, emphasizing the importance of tracking predator diets before, during and after irruption events. PMID- 28989740 TI - Spreading of components of mood in adolescent social networks. AB - Recent research has provided evidence that mood can spread over social networks via social contagion, but that, in seeming contradiction to this, depression does not. Here, we investigate whether there is evidence for the individual components of mood (such as appetite, tiredness and sleep) spreading through US adolescent friendship networks while adjusting for confounding by modelling the transition probabilities of changing mood state over time. We find that having more friends with worse mood is associated with a higher probability of an adolescent worsening in mood and a lower probability of improving, and vice versa for friends with better mood, for the overwhelming majority of mood components. We also show, however, that this effect is not strong enough in the negative direction to lead to a significant increase in depression incidence, helping to resolve the seeming contradictory nature of existing research. Our conclusions, therefore, link in to current policy discussions on the importance of subthreshold levels of depressive symptoms and could help inform interventions against depression in high schools. PMID- 28989741 TI - Cu1-x Fe x O: hopping transport and ferromagnetism. AB - Single phase, sol-gel prepared Cu1-x Fe x O (0 <= x <= 0.125) powders are characterized in terms of structural, electronic and magnetic properties. Using dielectric and magnetic studies we investigate the coupling of electron and spin. The electrical conductivities and activation energies are studied with increasing Fe content. Modelling of experimental conductivity data emphasizes a single hopping mechanism for all samples except x = 0.125, which have two activation energies. Hole doping is confirmed by confirming a majority Fe3+ substitution of Cu2+ in CuO from X-ray photoelectron spectroscopy studies (XPS). Such a substitution results in stabilized ferromagnetism. Fe substitution introduces variation in coercivity as an intrinsic magnetic property in Fe-doped CuO, and not as a secondary impurity phase. PMID- 28989742 TI - Comparative studies need to rely both on sound natural history data and on excellent statistical analysis. PMID- 28989743 TI - Improved surface-enhanced Raman and catalytic activities of reduced graphene oxide-osmium hybrid nano thin films. AB - Reduced graphene oxide-osmium (rGO-Os) hybrid nano dendtrites have been prepared by simple liquid/liquid interface method for the first time. The method involves the introduction of phase-transfered metal organic precursor in toluene phase and GO dispersion in the aqueous phase along with hydrazine hydrate as the reducing agent. Dendritic networks of Os nanoparticles and their aggregates decorating rGO layers are obtained. The substrate shows improved catalytic and surface-enhanced activities comparable with previous reports. The catalytic activity was tested for the reduction of p-nitroaniline into p-phenyldiamine with an excess amount of NaBH4. The catalytic activity factors of these hybrid films are 2.3 s-1 g-1 (Os film) and 4.4 s-1 g-1 (rGO-Os hybrid film), which are comparable with other noble metal nanoparticles such as Au, Ag, but lower than Pd-based catalysts. Surface enhanced Raman spectroscopy (SERS) measurements have been done on rhodamine 6G (R6G) and methylene blue dyes. The enhancement factor for the R6G adsorbed on rGO Os thin film is 1.0 * 105 and for Os thin film is 7 * 103. There is a 14-fold enhancement observed for Os hybrids with rGO. The enhanced catalytic and SERS activities of rGO-Os hybrid thin film prepared by simple liquid/liquid interface method open up new challenges in electrocatalytic application and SERS-based detection of biomolecules. PMID- 28989744 TI - Mixed-matrix membranes with enhanced antifouling activity: probing the surface tailoring potential of Tiron and chromotropic acid for nano-TiO2. AB - Mixed-matrix membranes (MMMs) were developed by impregnating organofunctionalized nanoadditives within fouling-susceptible polysulfone matrix following the non solvent induced phase separation (NIPS) method. The facile functionalization of nanoparticles of anatase TiO2 (nano-TiO2) by using two different organoligands, viz. Tiron and chromotropic acid, was carried out to obtain organofunctionalized nanoadditives, FT-nano-TiO2 and FC-nano-TiO2, respectively. The structural features of nanoadditives were evaluated by X-ray diffraction, X-ray photoelectron spectroscopy, Raman and Fourier transform infrared spectroscopy, which established that Tiron leads to the blending of chelating and bridging bidentate geometries for FT-nano-TiO2, whereas chromotropic acid produces bridging bidentate as well as monodentate geometries for FC-nano-TiO2. The surface chemistry of the studied membranes, polysulfone (Psf): FT-nano-TiO2 UF and Psf: FC-nano-TiO2 UF, was profoundly influenced by the benign distributions of the nanoadditives enriched with distinctly charged sites ([Formula: see text]), as evidenced by superior morphology, improved topography, enhanced surface hydrophilicity and altered electrokinetic features. The membranes exhibited enhanced solvent throughputs, viz. 3500-4000 and 3400-4300 LMD at 1 bar of transmembrane pressure, without significant compromise in their rejection attributes. The flux recovery ratios and fouling resistive behaviours of MMMs towards bovine serum albumin indicated that the nanoadditives could impart stable and appreciable antifouling activity, potentially aiding in a sustainable ultrafiltration performance. PMID- 28989745 TI - Spatial capture-recapture analysis of artificial cover board survey data reveals small scale spatial variation in slow-worm Anguis fragilis density. AB - Vague and/or ad hoc definitions of the area sampled in monitoring efforts are common, and estimates of ecological state variables (e.g. distribution and abundance) can be sensitive to such specifications. The uncertainty in population metrics due to data deficiencies, vague definitions of space and lack of standardized protocols is a major challenge for monitoring, managing and conserving amphibian and reptile populations globally. This is especially true for the slow-worm (Anguis fragilis), a cryptic and fossorial legless lizard; uncertainty about spatial variation in density has hindered conservation efforts (e.g. in translocation projects). Spatial capture-recapture (SCR) methods can be used to estimate density while simultaneously and explicitly accounting for space and individual movement. We use SCR to analyse mark-recapture data of the slow worm that were collected using artificial cover objects (ACO). Detectability varied among ACO grids and through the season. Estimates of slow-worm density varied across ACO grids (13, 45 and 46 individuals ha-1, respectively). The estimated 95% home range size of slow-worms was 0.38 ha. Our estimates provide valuable information about slow-worm spatial ecology that can be used to inform future conservation management. PMID- 28989747 TI - Molecular trade-offs in RNA ligases affected the modular emergence of complex ribozymes at the origin of life. AB - In the RNA world hypothesis complex, self-replicating ribozymes were essential. For the emergence of an RNA world, less is known about the early processes that accounted for the formation of complex, long catalysts from small passively formed molecules. The functional role of small sequences has not been fully explored and, here, a possible role for smaller ligases is demonstrated. An established RNA polymerase model, the R18, was truncated from the 3' end to generate smaller molecules. All the molecules were investigated for self-ligation functions with a set of oligonucleotide substrates without predesigned base pairing. The smallest molecule that exhibited self-ligation activity was a 40 nucleotide RNA. It also demonstrated the greatest functional flexibility as it was more general in the kinds of substrates it ligated to itself although its catalytic efficiency was the lowest. The largest ribozyme (R18) ligated substrates more selectively and with greatest efficiency. With increase in size and predicted structural stability, self-ligation efficiency improved, while functional flexibility decreased. These findings reveal that molecular size could have increased from the activity of small ligases joining oligonucleotides to their own end. In addition, there is a size-associated molecular-level trade-off that could have impacted the evolution of RNA-based life. PMID- 28989748 TI - Magic informationally complete POVMs with permutations. AB - Eigenstates of permutation gates are either stabilizer states (for gates in the Pauli group) or magic states, thus allowing universal quantum computation (Planat, Rukhsan-Ul-Haq 2017 Adv. Math. Phys. 2017, 5287862 (doi:10.1155/2017/5287862)). We show in this paper that a subset of such magic states, when acting on the generalized Pauli group, define (asymmetric) informationally complete POVMs. Such informationally complete POVMs, investigated in dimensions 2-12, exhibit simple finite geometries in their projector products and, for dimensions 4 and 8 and 9, relate to two-qubit, three-qubit and two qutrit contextuality. PMID- 28989746 TI - The sex-specific effects of diet quality versus quantity on morphology in Drosophila melanogaster. AB - Variation in the quality and quantity of nutrition is a major contributor to phenotypic variation in animal populations. Although we know much of how dietary restriction impacts phenotype, and of the molecular-genetic and physiological mechanisms that underlie this response, we know much less of the effects of dietary imbalance. Specifically, although dietary imbalance and restriction both reduce overall body size, it is unclear whether both have the same effect on the size of individual traits. Here, we use the fruit fly Drosophila melanogaster to explore the effect of dietary food versus protein-to-carbohydrate ratio on body proportion and trait size. Our results indicate that body proportion and trait size respond differently to changes in diet quantity (food concentration) versus diet quality (protein-to-carbohydrate ratio), and that these effects are sex specific. While these differences suggest that Drosophila use at least partially distinct developmental mechanisms to respond to diet quality versus quantity, further analysis indicates that the responses can be largely explained by the independent and contrasting effects of protein and carbohydrate concentration on trait size. Our data highlight the importance of considering macronutrient composition when elucidating the effect of nutrition on trait size, at the levels of both morphology and developmental physiology. PMID- 28989749 TI - A geometric method for eigenvalue problems with low-rank perturbations. AB - We consider the problem of finding the spectrum of an operator taking the form of a low-rank (rank one or two) non-normal perturbation of a well-understood operator, motivated by a number of problems of applied interest which take this form. We use the fact that the system is a low-rank perturbation of a solved problem, together with a simple idea of classical differential geometry (the envelope of a family of curves) to completely analyse the spectrum. We use these techniques to analyse three problems of this form: a model of the oculomotor integrator due to Anastasio & Gad (2007 J. Comput. Neurosci.22, 239-254. (doi:10.1007/s10827-006-0010-x)), a continuum integrator model, and a non-local model of phase separation due to Rubinstein & Sternberg (1992 IMA J. Appl. Math.48, 249-264. (doi:10.1093/imamat/48.3.249)). PMID- 28989750 TI - Feeding the world's largest fish: highly variable whale shark residency patterns at a provisioning site in the Philippines. AB - Provisioning wildlife for tourism is a controversial yet widespread practice. We analysed the residency patterns of juvenile whale sharks (Rhincodon typus) in Oslob, Philippines, where provisioning has facilitated a large shark-watching operation since 2011. We identified 208 individual sharks over three years, with an average of 18.6 (s.d. = 7.8, range = 6-43) individuals sighted per week. Weekly shark abundance varied seasonally and peak-season abundance (approx. May November) increased across years. Whale sharks displayed diverse individual site visitation patterns ranging from a single visit to sporadic visits, seasonal residency and year-round residency. Nine individuals became year-round residents, which represents a clear response to provisioning. The timing of the seasonal peak at Oslob did not align with known non-provisioned seasonal aggregations elsewhere in the Philippines, which could suggest that seasonal residents at Oslob exploit this food source when prey availability at alternative sites is low. Since prolonged residency equates to less time foraging naturally, provisioning could influence foraging success, alter distributions and lead to dependency in later life stages. Such impacts must be carefully weighed against the benefits of provisioning (i.e. tourism revenue in a remote community) to facilitate informed management decisions. PMID- 28989752 TI - Cultural investment and urban socio-economic development: a geosocial network approach. AB - Being able to assess the impact of government-led investment onto socio-economic indicators in cities has long been an important target of urban planning. However, owing to the lack of large-scale data with a fine spatio-temporal resolution, there have been limitations in terms of how planners can track the impact and measure the effectiveness of cultural investment in small urban areas. Taking advantage of nearly 4 million transition records for 3 years in London from a popular location-based social network service, Foursquare, we study how the socio-economic impact of government cultural expenditure can be detected and predicted. Our analysis shows that network indicators such as average clustering coefficient or centrality can be exploited to estimate the likelihood of local growth in response to cultural investment. We subsequently integrate these features in supervised learning models to infer socio-economic deprivation changes for London's neighbourhoods. This research presents how geosocial and mobile services can be used as a proxy to track and predict socio-economic deprivation changes as government financial effort is put in developing urban areas and thus gives evidence and suggestions for further policymaking and investment optimization. PMID- 28989751 TI - Characterization and Pb(II) removal potential of corn straw- and municipal sludge derived biochars. AB - Corn straw- and municipal sludge-derived biochars (CS-BC and MS-BC, respectively) were used to remove Pb(II) from aqueous solutions. Despite being pyrolysed at the same temperature (723 K), MS-BC showed higher porosity and hydrophobicity than CS BC. The optimum biochar loading and pH values allowing efficient Pb(II) removal (greater than 80%) were 0.2 g l-1 and 7.0, respectively. The presence of PO43- (greater than 0.01 mol l-1) significantly affected the adsorptive performance of Pb(II) on the biochar samples. The adsorption data fitted well to a pseudo-second order kinetic model and a Langmuir model, and the maximum Pb(II) adsorption capacities were 352 and 387 mg g-1 for CS-BC and MS-BC, respectively. The main mechanisms involved in the adsorption of Pb(II) on biochar were electrostatic attraction and surface complexation. When comparing both biochars, CS-BC showed better cost-effectiveness for the removal of Pb(II) from aqueous solutions. PMID- 28989753 TI - Influence of solvents in the preparation of cobalt sulfide for supercapacitors. AB - In this study, cobalt sulfide (CoS) electrodes are synthesized using various solvents such as water, ethanol and a combination of the two via a facile chemical bath deposition method on Ni foam. The crystalline nature, chemical states and surface morphology of the prepared CoS nanoparticles are characterized using X-ray diffraction, X-ray photoelectron spectroscopy, scanning electron microscopy and transition electron microscopy. The electrochemical properties of CoS electrodes are also evaluated using cyclic voltammetry, galvanostatic charge discharge and electrochemical impedance spectroscopy. When used as an electrode for a supercapacitor, CoS prepared with ethanol as a solvent exhibits a capacitance of 41.36 F g-1 at 1.5 A g-1, which is significantly better than that prepared using water and water/ethanol-based solvents (31.66 and 18.94 F g-1 at 1.5 A g-1, respectively). This superior capacitance is attributed to the ideal surface morphology of the solvent, which allows for easy diffusion of electrolyte ions into the inner region of the electrode. High electrical conduction enables a high rate capability. These results suggest that CoS nanoparticles are highly promising for energy storage applications as well as photocatalysis, electrocatalysis, water splitting and solar cells, among others. These results show that CoS is a promising positive electrode material for practical supercapacitors. PMID- 28989754 TI - Accelerating adaptive inverse distance weighting interpolation algorithm on a graphics processing unit. AB - This paper focuses on designing and implementing parallel adaptive inverse distance weighting (AIDW) interpolation algorithms by using the graphics processing unit (GPU). The AIDW is an improved version of the standard IDW, which can adaptively determine the power parameter according to the data points' spatial distribution pattern and achieve more accurate predictions than those predicted by IDW. In this paper, we first present two versions of the GPU accelerated AIDW, i.e. the naive version without profiting from the shared memory and the tiled version taking advantage of the shared memory. We also implement the naive version and the tiled version using two data layouts, structure of arrays and array of aligned structures, on both single and double precision. We then evaluate the performance of parallel AIDW by comparing it with its corresponding serial algorithm on three different machines equipped with the GPUs GT730M, M5000 and K40c. The experimental results indicate that: (i) there is no significant difference in the computational efficiency when different data layouts are employed; (ii) the tiled version is always slightly faster than the naive version; and (iii) on single precision the achieved speed-up can be up to 763 (on the GPU M5000), while on double precision the obtained highest speed-up is 197 (on the GPU K40c). To benefit the community, all source code and testing data related to the presented parallel AIDW algorithm are publicly available. PMID- 28989755 TI - Facilitation of trace metal uptake in cells by inulin coating of metallic nanoparticles. AB - Trace elements such as zinc and iron are essential for the proper function of biochemical processes, and their uptake and bioavailability are dependent on their chemical form. Supplementation of trace metals through nanostructured materials is a new field, but its application raises concerns regarding their toxicity. Here, we compared the intracellular zinc uptake of different sources of zinc: zinc sulfate, and ZnO and core-shell alpha-Fe2O3@ZnO nanoparticles, coated or uncoated with inulin, an edible and biocompatible polysaccharide. Using mussel haemocytes, a well-known model system to assess nanomaterial toxicity, we simultaneously assessed zinc accumulation and multiple cellular response endpoints. We found that intracellular zinc uptake was strongly enhanced by inulin coating, in comparison to the uncoated nanoparticles, while no significant effects on cell death, cell viability, mitochondrial membrane integrity, production of reactive oxygen species or lysosome abundance were observed at concentrations up to 20 ppm. Since no significant increments in toxicity were observed, the coated nanomaterials may be useful to increase in vivo zinc uptake for nutritional applications. PMID- 28989756 TI - Does detection range matter for inferring social networks in a benthic shark using acoustic telemetry? AB - Accurately estimating contacts between animals can be critical in ecological studies such as examining social structure, predator-prey interactions or transmission of information and disease. While biotelemetry has been used successfully for such studies in terrestrial systems, it is still under development in the aquatic environment. Acoustic telemetry represents an attractive tool to investigate spatio-temporal behaviour of marine fish and has recently been suggested for monitoring underwater animal interactions. To evaluate the effectiveness of acoustic telemetry in recording interindividual contacts, we compared co-occurrence matrices deduced from three types of acoustic receivers varying in detection range in a benthic shark species. Our results demonstrate that (i) associations produced by acoustic receivers with a large detection range (i.e. Vemco VR2W) were significantly different from those produced by receivers with smaller ranges (i.e. Sonotronics miniSUR receivers and proximity loggers) and (ii) the position of individuals within their network, or centrality, also differed. These findings suggest that acoustic receivers with a large detection range may not be the best option to represent true social networks in the case of a benthic marine animal. While acoustic receivers are increasingly used by marine ecologists, we recommend users first evaluate the influence of detection range to depict accurate individual interactions before using these receivers for social or predator-prey studies. We also advocate for combining multiple receiver types depending on the ecological question being asked and the development of multi-sensor tags or testing of new automated proximity loggers, such as the Encounternet system, to improve the precision and accuracy of social and predator-prey interaction studies. PMID- 28989757 TI - Limited evidence for third-party affiliation during development in wild chimpanzees (Pan troglodytes schweinfurthii). AB - Examining the ontogeny of conflict-mitigating behaviours in our closest living relatives is an important component of understanding the evolutionary origins of cooperation in our species. In this study, we used 26 years of data to investigate the emergence of third-party affiliation (TPA), defined as affiliative contact given to recipients of aggression by uninvolved bystanders (regardless of initiation), in wild immature eastern chimpanzees (Pan troglodytes schweinfurthii) of Gombe National Park, Tanzania. We also characterized TPA by mothers in the same dataset as an adult benchmark for interpreting immature TPA patterns. In summary, we found that immatures did not express TPA as measured by grooming between the ages of 1.5 and 12.0 years, and that there was limited evidence that immatures expressed TPA via play. We also found that mothers did express TPA to offspring, although mothers did not show TPA towards non offspring. Cases of TPA by mothers to other adults were too few to analyse separately. These results contrast with findings from captive studies which found that chimpanzees as young as 6 years of age demonstrated TPA. We argue that within-species variation in the expression of TPA, both in immatures and adulthood, provides evidence that the conflict management behaviours of young chimpanzees may be heavily influenced by social, ecological and demographic factors. PMID- 28989758 TI - Design of cinnamaldehyde amino acid Schiff base compounds based on the quantitative structure-activity relationship. AB - Cinnamaldehyde amino acid Schiff base (CAAS) is a new class of safe, bioactive compounds which could be developed as potential antifungal agents for fungal infections. To design new cinnamaldehyde amino acid Schiff base compounds with high bioactivity, the quantitative structure-activity relationships (QSARs) for CAAS compounds against Aspergillus niger (A. niger) and Penicillium citrinum (P. citrinum) were analysed. The QSAR models (R2 = 0.9346 for A. niger, R2 = 0.9590 for P. citrinum,) were constructed and validated. The models indicated that the molecular polarity and the Max atomic orbital electronic population had a significant effect on antifungal activity. Based on the best QSAR models, two new compounds were designed and synthesized. Antifungal activity tests proved that both of them have great bioactivity against the selected fungi. PMID- 28989759 TI - Population cycles emerging through multiple interaction types. AB - Cyclic dynamics of populations are outstanding and widespread phenomena across many taxa. Previous theoretical studies have mainly focused on the consumer resource interaction as the driving force for such cycling. However, natural ecosystems comprise diverse types of species interactions, but their roles in population dynamics remains unclear. Here, using a four-species hybrid module with antagonistic, mutualistic and competitive interactions, we analytically showed that the system with major interaction types can drive population cycles. Stronger interactions easily cause cycling, and even when sub-modules with possible combinations of two interactions are stabilized by weak interactions, the system with all interaction types can cause unstable population oscillations. Diversity of interaction types allows to add mutualists to the list of drivers of oscillations in a focal species' population size, when they act in conjunction to other drivers. PMID- 28989760 TI - Performance improvement of miniaturized ZnO nanowire accelerometer fabricated by refresh hydrothermal synthesis. AB - Miniaturized accelerometers are necessary for evaluating the performance of small devices, such as haptics, robotics and simulators. In this study, we fabricated miniaturized accelerometers using well-aligned ZnO nanowires. The layer of ZnO nanowires is used for active piezoelectric layer of the accelerometer, and copper was chosen as a head mass. Seedless and refresh hydrothermal synthesis methods were conducted to grow ZnO nanowires on the copper substrate and the effect of ZnO nanowire length on the accelerometer performance was investigated. The refresh hydrothermal synthesis exhibits longer ZnO nanowires, 12 um, than the seedless hydrothermal synthesis, 6 um. Performance of the fabricated accelerometers was verified by comparing with a commercial accelerometer. The sensitivity of the fabricated accelerometer by the refresh hydrothermal synthesis is shown to be 37.7 pA g-1, which is about 30 times larger than the previous result. PMID- 28989761 TI - A new Miocene baleen whale from Peru deciphers the dawn of cetotheriids. AB - Cetotheriidae are an iconic, nearly extinct family of baleen whales (Mysticeti) with a highly distinct cranial morphology. Their origins remain a mystery, with even the most archaic species showing a variety of characteristic features. Here, we describe a new species of archaic cetotheriid, Tiucetus rosae, from the Miocene of Peru. The new material represents the first mysticete from the poorly explored lowest portion of the highly fossiliferous Pisco Formation (allomember P0), and appears to form part of a more archaic assemblage than observed at the well-known localities of Cerro Colorado, Cerro los Quesos, Sud-Sacaco and Aguada de Lomas. Tiucetus resembles basal plicogulans (crown Mysticeti excluding right whales), such as Diorocetus and Parietobalaena, but shares with cetotheriids a distinct morphology of the auditory region, including the presence of an enlarged paroccipital concavity. The distinctive morphology of Tiucetus firmly places Cetotheriidae in the context of the poorly understood 'cetotheres' sensu lato, and helps to resolve basal relationships within crown Mysticeti. PMID- 28989762 TI - Adsorption and movement of water by skin of the Australian thorny devil (Agamidae: Moloch horridus). AB - Moisture-harvesting lizards, such as the Australian thorny devil Moloch horridus, have remarkable adaptations for inhabiting arid regions. Their microstructured skin surface, with channels in between overlapping scales, enables them to collect water by capillarity and passively transport it to the mouth for ingestion. We characterized this capillary water transport for live thorny devils using high-speed video analyses. Comparison with preserved specimens showed that live lizards are required for detailed studies of skin water transport. For thorny devils, there was no directionality in cutaneous water transport (unlike Phrynosoma) as 7 ul water droplets applied to the skin were transported radially over more than 9.2 mm. We calculated the total capillary volume as 5.76 ul cm-2 (dorsal) and 4.45 ul cm-2 (ventral), which is reduced to 50% filling by the time transportation ceases. Using micro-computed tomography and scanning electron microscopy of shed skin to investigate capillary morphology, we found that the channels are hierarchically structured as a large channel between the scales that is sub-divided by protrusions into smaller sub-capillaries. The large channel quickly absorbs water whereas the sub-capillary structure extends the transport distance by about 39% and potentially reduces the water volume required for drinking. An adapted dynamics function, which closely reflects the channel morphology, includes that ecological role. PMID- 28989764 TI - Modelling personality, plasticity and predictability in shelter dogs. AB - Behavioural assessments of shelter dogs (Canis lupus familiaris) typically comprise standardized test batteries conducted at one time point, but test batteries have shown inconsistent predictive validity. Longitudinal behavioural assessments offer an alternative. We modelled longitudinal observational data on shelter dog behaviour using the framework of behavioural reaction norms, partitioning variance into personality (i.e. inter-individual differences in behaviour), plasticity (i.e. inter-individual differences in average behaviour) and predictability (i.e. individual differences in residual intra-individual variation). We analysed data on interactions of 3263 dogs (n = 19 281) with unfamiliar people during their first month after arrival at the shelter. Accounting for personality, plasticity (linear and quadratic trends) and predictability improved the predictive accuracy of the analyses compared to models quantifying personality and/or plasticity only. While dogs were, on average, highly sociable with unfamiliar people and sociability increased over days since arrival, group averages were unrepresentative of all dogs and predictions made at the individual level entailed considerable uncertainty. Effects of demographic variables (e.g. age) on personality, plasticity and predictability were observed. Behavioural repeatability was higher one week after arrival compared to arrival day. Our results highlight the value of longitudinal assessments on shelter dogs and identify measures that could improve the predictive validity of behavioural assessments in shelters. PMID- 28989763 TI - Into the dark: patterns of middle ear adaptations in subterranean eulipotyphlan mammals. AB - Evolution of the middle ear ossicles was a key innovation for mammals, enhancing the transmission of airborne sound. Radiation into various habitats from a terrestrial environment resulted in diversification of the auditory mechanisms among mammals. However, due to the paucity of phylogenetically controlled investigations, how middle ear traits have diversified with functional specialization remains unclear. In order to identify the respective patterns for various lifestyles and to gain insights into fossil forms, we employed a high resolution tomography technique and compared the middle ear morphology of eulipotyphlan species (moles, shrews and hedgehogs), a group that has radiated into various environments, such as terrestrial, aquatic and subterranean habitats. Three-dimensional geometric morphometric analysis was conducted within a phylogenetically controlled framework. Quantitative shapes were found to strongly reflect the degree of subterranean lifestyle and weakly involve phylogeny. Our analyses demonstrate that subterranean adaptation should include a relatively shorter anterior process of the malleus, an enlarged incus, an enlarged stapes footplate and a reduction of the orbicular apophysis. These traits arguably allow improving low-frequency sound transmission at low frequencies and inhibiting the low-frequency noise which disturbs the subterranean animals in hearing airborne sounds. PMID- 28989766 TI - Larval abundances of rockfishes that were historically targeted by fishing increased over 16 years in association with a large marine protected area. AB - Marine protected areas (MPAs) can facilitate recovery of diminished stocks by protecting reproductive adults. To effectively augment fisheries, however, reproductive output must increase within the bounds of MPAs so that larvae can be exported to surrounding areas and seed the region. In response to dramatic declines of rockfishes (Sebastes spp.) in southern California by the late 1990s two large MPAs, the Cowcod Conservation Areas (CCAs), were established in 2001. To evaluate whether the CCAs affected rockfish productivity we evaluated the dynamics of 8 species that were, and 7 that were not, historically targeted by fishing. Abundances of 6/8 targeted and 4/7 non-targeted species increased regionally from 1998 to 2013. These upturns were probably affected by environmental conditions in addition to changes in fishing pressure as the presence of most species correlated negatively with temperature, and temperature was lower than the historic average in 11/15 years. Seventy-five per cent of the targeted, but none of the non-targeted species increased at a greater rate inside than outside the CCAs while controlling for environmental factors. Results indicate that management actions, coupled with favourable environmental conditions, facilitated the resurgence of multiple rockfish species that were targeted by intense fishing effort for decades. PMID- 28989765 TI - Architecture of crossed-lamellar bivalve shells: the southern giant clam (Tridacna derasa, Roding, 1798). AB - Tridacna derasa shells show a crossed lamellar microstructure consisting of three hierarchical lamellar structural orders. The mineral part is intimately intergrown with 0.9 wt% organics, namely polysaccharides, glycosylated and unglycosylated proteins and lipids, identified by Fourier transform infrared spectrometry. Transmission electron microscopy shows nanometre-sized grains with irregular grain boundaries and abundant voids. Twinning is observed across all spatial scales and results in a spread of the crystal orientation angles. Electron backscatter diffraction analysis shows a strong fibre texture with the [001] axes of aragonite aligned radially to the shell surface. The aragonitic [100] and [010] axes are oriented randomly around [001]. The random orientation of anisotropic crystallographic directions in this plane reduces anisotropy of the Young's modulus and adds to the optimization of mechanical properties of bivalve shells. PMID- 28989767 TI - Pedestrian motion modelled by Fokker-Planck Nash games. AB - A new approach to modelling pedestrians' avoidance dynamics based on a Fokker Planck (FP) Nash game framework is presented. In this framework, two interacting pedestrians are considered, whose motion variability is modelled through the corresponding probability density functions (PDFs) governed by FP equations. Based on these equations, a Nash differential game is formulated where the game strategies represent controls aiming at avoidance by minimizing appropriate collision cost functionals. The existence of Nash equilibria solutions is proved and characterized as a solution to an optimal control problem that is solved numerically. Results of numerical experiments are presented that successfully compare the computed Nash equilibria to the output of real experiments (conducted with humans) for four test cases. PMID- 28989768 TI - Function and flexibility of object exploration in kea and New Caledonian crows. AB - A range of non-human animals frequently manipulate and explore objects in their environment, which may enable them to learn about physical properties and potentially form more abstract concepts of properties such as weight and rigidity. Whether animals can apply the information learned during their exploration to solve novel problems, however, and whether they actually change their exploratory behaviour to seek functional information about objects have not been fully explored. We allowed kea (Nestor notabilis) and New Caledonian crows (Corvus moneduloides) to explore sets of novel objects both before and after encountering a task in which some of the objects could function as tools. Following this, subjects were given test trials in which they could choose among the objects they had explored to solve a tool-use task. Several individuals from both species performed above chance on these test trials, and only did so after exploring the objects, compared with a control experiment with no prior exploration phase. These results suggest that selection of functional tools may be guided by information acquired during exploration. Neither kea nor crows changed the duration or quality of their exploration after learning that the objects had a functional relevance, suggesting that birds do not adjust their behaviour to explicitly seek this information. PMID- 28989769 TI - Highly efficient synthesis of [60]fullerene oxides by plasma jet. AB - Atmospheric pressure nonequilibrium plasma jet has been applied to the synthesis of [60]fullerene oxides (C60On) for the first time. C60O and C60O2 were produced and isolated in high yields up to 44% and 21%, respectively. The structural assignment of C60O was confirmed by comparison with the reported spectroscopic data. Theoretical calculations of 13C NMR chemical shifts for eight isomers of C60O2 were performed and compared with the experimental data to assign the most possible structure for the obtained C60O2 dominantly as an e isomer. PMID- 28989770 TI - Large batoid fishes frequently consume stingrays despite skeletal damage. AB - The shapes of vertebrate teeth are often used as hallmarks of diet. Here, however, we demonstrate evidence of frequent piscivory by cartilaginous fishes with pebble-like teeth that are typically associated with durophagy, the eating of hard-shelled prey. High-resolution micro-computed tomography observation of a jaw specimen from one batoid species and visual investigation of those of two additional species reveal large numbers of embedded stingray spines, arguing that stingray predation of a scale rivalling that of the largest carnivorous sharks may not be uncommon for large, predatory batoids with rounded, non-cutting dentition. Our observations demonstrate that tooth morphology is not always a reliable indicator of diet and that stingray spines are not as potent a deterrent to predation as normally believed. In addition, we show that several spines in close contact with the jaw skeleton of a wedgefish (Rhynchobatus) have become encased in a disorganized mineralized tissue with a distinctive ultrastructure, the first natural and unequivocal evidence of a callus-building response in the tessellated cartilage unique to elasmobranch skeletons. Our findings reveal sampling and analysis biases in vertebrate ecology, especially with regard to the role of large, predatory species, while also illustrating that large body size may provide an escape from anatomical constraints on diet (e.g. gape size, specialist dentition). Our observations inform our concepts of skeletal biology and evolution in showing that tessellated cartilage-an ancient alternative to bone-is incapable of foreign tissue resorption or of restoring damaged skeletal tissue to its original state, and attest to the value of museum and skeletal specimens as records of important aspects of animal life history. PMID- 28989771 TI - Preparation of core-shell structured CaCO3 microspheres as rapid and recyclable adsorbent for anionic dyes. AB - Core-shell structured CaCO3 microspheres (MSs) were prepared by a facile, one-pot method at room temperature. The adsorbent dosage and adsorption time of the obtained CaCO3 MSs were investigated. The results suggest that these CaCO3 MSs can rapidly and efficiently remove 99-100% of anionic dyes within the first 2 min. The obtained CaCO3 MSs have a high Brunauer-Emmett-Teller surface area (211.77 m2 g-1). In addition, the maximum adsorption capacity of the obtained CaCO3 MSs towards Congo red was 99.6 mg g-1. We also found that the core-shell structured CaCO3 MSs have a high recycling capability for removing dyes from water. Our results demonstrate that the prepared core-shell structured CaCO3 MSs can be used as an ideal, rapid, efficient and recyclable adsorbent to remove dyes from aqueous solution. PMID- 28989772 TI - Dielectric properties and carbothermic reduction of zinc oxide and zinc ferrite by microwave heating. AB - This paper aims to study the dielectric properties and carbothermic reduction of zinc oxide (zincite, ZnO) and zinc ferrite (franklinite, ZnFe2O4) by microwave heating. To achieve this aim, the dielectric properties were measured with an open-ended coaxial method to understand the behaviour of the samples under microwave irradiation. The effects of microwave power, duration time and sample mass on the heating rate, and the effects of the stoichiometric amount of graphite on the reduction of ZnO and decomposition of ZnFe2O4 were investigated. The results show that ZnFe2O4 has significantly higher dielectric properties compared to ZnO. Generally, for both samples, the dielectric values at room temperature were quite low, indicating that both ZnO and ZnFe2O4 are poor microwave absorbers. It was found that the temperatures have a more significant effect on the imaginary permittivities than on the real permittivities. The heating rate showed that the sample temperature increased with increase in microwave power and sample mass. Using 700 W of microwave power and two times the stoichiometric amount of graphite, almost complete reduction of ZnO was achieved in 12 min, while ZnFe2O4 completely decomposed to zincite and wustite in 3 min. PMID- 28989773 TI - A generalized equation for the calculation of receptor noise limited colour distances in n-chromatic visual systems. AB - Researchers must assess similarities and differences in colour from an animal's eye view when investigating hypotheses in ecology, evolution and behaviour. Nervous systems generate colour perceptions by comparing the responses of different spectral classes of photoreceptor through colour opponent mechanisms, and the performance of these mechanisms is limited by photoreceptor noise. Accordingly, the receptor noise limited (RNL) colour distance model of Vorobyev and Osorio (Vorobyev & Osorio 1998 Proc. R. Soc. Lond. B265, 351-358 (doi:10.1098/rspb.1998.0302)) generates predictions about the discriminability of colours that agree with behavioural data, and consequently it has found wide application in studies of animal colour vision. Vorobyev and Osorio (1998) provide equations to calculate RNL colour distances for animals with di-, tri- and tetrachromatic vision, which is adequate for many species. However, researchers may sometimes wish to compute RNL colour distances for potentially more complex colour visual systems. Thus, we derive a simple, single formula for the computation of RNL distance between two measurements of colour, equivalent to the published di-, tri- and tetrachromatic equations of Vorobyev and Osorio (1998), and valid for colour visual systems with any number of types of noisy photoreceptors. This formula will allow the easy application of this important colour visual model across the fields of ecology, evolution and behaviour. PMID- 28989774 TI - Extraction of lotus fibres from lotus stems under microwave irradiation. AB - An efficient technology for preparing lotus fibres under microwave irradiation was developed. The lotus fibres were characterized by scanning electron microscopy, Fourier transform infrared spectrometry, X-ray diffraction and thermogravimetry. Lotus fibres prepared are a kind of hollow fibres which are composed of a superfine fibre and an external shell. The effect of the treatment time with hydrogen peroxide under microwave irradiation on components, whiteness, moisture regain, removal rate of impurities, fineness, tensile strength and breaking elongation of lotus fibres was investigated. The results show that the cellulose content in lotus fibres increases with increase in treatment time. Whiteness and moisture regain of lotus fibres increase with increase in treatment time with hydrogen peroxide. The removal rate of impurities and the fineness of lotus fibres are improved after they are treated with hydrogen peroxide. Microwave irradiation is supposed to be an efficient method for producing lotus fibres. PMID- 28989775 TI - Celebrating 30 years of science from the James Clerk Maxwell Telescope. AB - The James Clerk Maxwell Telescope (JCMT) has been the world's most successful single-dish telescope at submillimetre wavelengths since it began operations in 1987. From the pioneering days of single-element photometers and mixers, through to the state-of-the-art imaging and spectroscopic cameras, the JCMT has been associated with a number of major scientific discoveries. Famous for the discovery of 'SCUBA' galaxies, which are responsible for a large fraction of the far-infrared background, the JCMT has pushed the sensitivity limits arguably more than any other facility in this most difficult of wavebands in which to observe. Closer to home, the first images of huge discs of cool debris around nearby stars gave us clues to the evolution of planetary systems, further evidence of the importance of studying astrophysics in the submillimetre region. Now approaching the 30th anniversary of the first observations, the telescope continues to carry out unique and innovative science. In this review article, we look back on some of the major scientific highlights from the past 30 years. PMID- 28989776 TI - Flexible transparent electrodes based on silver nanowires synthesized via a simple method. AB - Silver nanowires (Ag NWs) with the length of approximately 60 um and the diameter of approximately 300 nm are prepared via a simple, cost-effective, high-yield and eco-friendly procedure under a high molar concentration ratio of silver nitrate (AgNO3) solution to poly(vinyl pyrrolidone) solution. The pre-synthesized Ag NWs were analysed by scanning electron microscopy, X-ray diffraction and UV-visible spectrophotometer. Furthermore, the as-prepared silver nanowires were roll-coated on the surfaces of the polyethylene terephthalate (PET) substrates. By optimizing the concentration of silver nanowire solution, the flexible Ag NW/PET transparent electrodes with a sheet resistance of 3.8 Omega sq-1 at a transmittance of 70% can be fabricated. The results reported in this paper provide a basis for optimizing the growth of silver nanowires and performances of transparent electrodes. PMID- 28989777 TI - Defining the flexibility window in ordered aluminosilicate zeolites. AB - The flexibility window in zeolites was originally identified using geometric simulation as a hypothetical property of SiO2 systems. The existence of the flexibility window in hypothetical structures may help us to identify those we might be able to synthesize in the future. We have previously found that the flexibility window in silicates is connected to phase transitions under pressure, structure amorphization and other physical behaviours and phenomena. We here extend the concept to ordered aluminosilicate systems using softer 'bar' constraints that permit additional flexibility around aluminium centres. Our experimental investigation of pressure-induced amorphization in sodalites is consistent with the results of our modelling. The softer constraints allow us to identify a flexibility window in the anomalous case of goosecreekite. PMID- 28989778 TI - Monarch butterfly population decline in North America: identifying the threatening processes. AB - The monarch butterfly (Danaus plexippus) population in North America has sharply declined over the last two decades. Despite rising concern over the monarch butterfly's status, no comprehensive study of the factors driving this decline has been conducted. Using partial least-squares regressions and time-series analysis, we investigated climatic and habitat-related factors influencing monarch population size from 1993 to 2014. Potential threats included climatic factors, habitat loss (milkweed and overwinter forest), disease and agricultural insecticide use (neonicotinoids). While climatic factors, principally breeding season temperature, were important determinants of annual variation in abundance, our results indicated strong negative relationships between population size and habitat loss variables, principally glyphosate use, but also weaker negative effects from the loss of overwinter forest and breeding season use of neonicotinoids. Further declines in population size because of glyphosate application are not expected. Thus, if remaining threats to habitat are mitigated we expect climate-induced stochastic variation of the eastern migratory population of monarch butterfly around a relatively stationary population size. PMID- 28989779 TI - Prostaglandin F2alpha synthase in Trypanosoma cruzi plays critical roles in oxidative stress and susceptibility to benznidazole. AB - Nifurtimox (Nfx) and benznidazole (Bz) are the current drugs used for the treatment of Chagas disease. The mechanisms of action and resistance to these drugs in this parasite are poorly known. Prostaglandin F2alpha synthase or old yellow enzyme (OYE), an NAD(P)H flavin oxidoreductase, has been involved in the activation pathway of other trypanocidal drugs such as Nfx; however, its role in the mechanism of action of Bz is uncertain. In this paper, we performed some experiments of functional genomics in the parasite Trypanosoma cruzi with the aim to test the role of this gene in the resistance to Bz. For this, we overexpressed this gene in sensitive parasites and evaluated the resistance level to the drug and other chemical compounds such as hydrogen peroxide, methyl methanesulfonate and gamma radiation. Interestingly, parasites overexpressing OYE showed alteration of enzymes associated with oxidative stress protection such as superoxide dismutase A and trypanothione reductase. Furthermore, transfected parasites were more sensitive to drugs, genetic damage and oxidative stress. Additionally, transfected parasites were less infective than wild-type parasites and they showed higher alteration in mitochondrial membrane potential and cell cycle after treatment with Bz. These results supply essential information to help further the understanding of the mechanism of action of Bz in T. cruzi. PMID- 28989780 TI - Huygens' clocks revisited. AB - In 1665, Huygens observed that two identical pendulum clocks, weakly coupled through a heavy beam, soon synchronized with the same period and amplitude but with the two pendula swinging in opposite directions. This behaviour is now called anti-phase synchronization. This paper presents an analysis of the behaviour of a large class of coupled identical oscillators, including Huygens' clocks, using methods of equivariant bifurcation theory. The equivariant normal form for such systems is developed and the possible solutions are characterized. The transformation of the physical system parameters to the normal form parameters is given explicitly and applied to the physical values appropriate for Huygens' clocks, and to those of more recent studies. It is shown that Huygens' physical system could only exhibit anti-phase motion, explaining why Huygens observed exclusively this. By contrast, some more recent researchers have observed in-phase or other more complicated motion in their own experimental systems. Here, it is explained which physical characteristics of these systems allow for the existence of these other types of stable solutions. The present analysis not only accounts for these previously observed solutions in a unified framework, but also introduces behaviour not classified by other authors, such as a synchronized toroidal breather and a chaotic toroidal breather. PMID- 28989781 TI - Benthic communities under anthropogenic pressure show resilience across the Quaternary. AB - The Southeast Pacific is characterized by rich upwelling systems that have sustained and been impacted by human groups for at least 12 ka. Recent fishing and aquaculture practices have put a strain on productive coastal ecosystems from Tongoy Bay, in north-central Chile. We use a temporal baseline to determine whether potential changes to community structure and composition over time are due to anthropogenic factors, natural climatic variations or both. We compiled a database (n = 33 194) with mollusc species abundances from the Mid-Pleistocene, Late Pleistocene, Holocene, dead shell assemblages and live-sampled communities. Species richness was not significantly different, neither were diversity and evenness indices nor rank abundance distributions. There is, however, an increase in relative abundance for the cultured scallop Argopecten, while the previously dominant clam Mulinia is locally very rare. Results suggest that impacts from both natural and anthropogenic stressors need to be better understood if benthic resources are to be preserved. These findings provide the first Pleistocene temporal baseline for the south Pacific that shows that this highly productive system has had the ability to recover from past alterations, suggesting that if monitoring and management practices continue to be implemented, moderately exploited communities from today have hopes for recovery. PMID- 28989782 TI - Breeding decisions and output are correlated with both temperature and rainfall in an arid-region passerine, the sociable weaver. AB - Animal reproductive cycles are commonly triggered by environmental cues of favourable breeding conditions. In arid environments, rainfall may be the most conspicuous cue, but the effects on reproduction of the high inter- and intra annual variation in temperature remain poorly understood, despite being relevant to the current context of global warming. Here, we conducted a multiyear examination of the relationships between a suite of measures of temperature and rainfall, and the onset and length of the breeding season, the probability of breeding and reproductive output in an arid-region passerine, the sociable weaver (Philetairus socius). As expected, reproductive output increased with rainfall, yet specific relationships were conditional on the timing of rainfall: clutch production was correlated with rainfall throughout the season, whereas fledgling production was correlated with early summer rainfall. Moreover, we reveal novel correlations between aspects of breeding and temperature, indicative of earlier laying dates after warmer springs, and longer breeding seasons during cooler summers. These results have implications for understanding population trends under current climate change scenarios and call for more studies on the role of temperature in reproduction beyond those conducted on temperate-region species. PMID- 28989783 TI - Genome size variation in deep-sea amphipods. AB - Genome size varies considerably across taxa, and extensive research effort has gone into understanding whether variation can be explained by differences in key ecological and life-history traits among species. The extreme environmental conditions that characterize the deep sea have been hypothesized to promote large genome sizes in eukaryotes. Here we test this supposition by examining genome sizes among 13 species of deep-sea amphipods from the Mariana, Kermadec and New Hebrides trenches. Genome sizes were estimated using flow cytometry and found to vary nine-fold, ranging from 4.06 pg (4.04 Gb) in Paralicella caperesca to 34.79 pg (34.02 Gb) in Alicella gigantea. Phylogenetic independent contrast analysis identified a relationship between genome size and maximum body size, though this was largely driven by those species that display size gigantism. There was a distinct shift in the genome size trait diversification rate in the supergiant amphipod A. gigantea relative to the rest of the group. The variation in genome size observed is striking and argues against genome size being driven by a common evolutionary history, ecological niche and life-history strategy in deep-sea amphipods. PMID- 28989784 TI - Glyph guessing for 'oo' and 'ee': spatial frequency information in sound symbolic matching for ancient and unfamiliar scripts. AB - In three experiments, we asked whether diverse scripts contain interpretable information about the speech sounds they represent. When presented with a pair of unfamiliar letters, adult readers correctly guess which is /i/ (the 'ee' sound in 'feet'), and which is /u/ (the 'oo' sound in 'shoe') at rates higher than expected by chance, as shown in a large sample of Singaporean university students (Experiment 1) and replicated in a larger sample of international Internet users (Experiment 2). To uncover what properties of the letters contribute to different scripts' 'guessability,' we analysed the visual spatial frequencies in each letter (Experiment 3). We predicted that the lower spectral frequencies in the formants of the vowel /u/ would pattern with lower spatial frequencies in the corresponding letters. Instead, we found that across all spatial frequencies, the letter with more black/white cycles (i.e. more ink) was more likely to be guessed as /u/, and the larger the difference between the glyphs in a pair, the higher the script's guessability. We propose that diverse groups of humans across historical time and geographical space tend to employ similar iconic strategies for representing speech in visual form, and provide norms for letter pairs from 56 diverse scripts. PMID- 28989785 TI - Group foraging increases foraging efficiency in a piscivorous diver, the African penguin. AB - Marine piscivores have evolved a variety of morphological and behavioural adaptations, including group foraging, to optimize foraging efficiency when targeting shoaling fish. For penguins that are known to associate at sea and feed on these prey resources, there is nonetheless a lack of empirical evidence to support improved foraging efficiency when foraging with conspecifics. We examined the hunting strategies and foraging performance of breeding African penguins equipped with animal-borne video recorders. Individuals pursued both solitary as well as schooling pelagic fish, and demonstrated independent as well as group foraging behaviour. The most profitable foraging involved herding of fish schools upwards during the ascent phase of a dive where most catches constituted depolarized fish. Catch-per-unit-effort was significantly improved when targeting fish schools as opposed to single fish, especially when foraging in groups. In contrast to more generalist penguin species, African penguins appear to have evolved specialist hunting strategies closely linked to their primary reliance on schooling pelagic fish. The specialist nature of the observed hunting strategies further limits the survival potential of this species if Allee effects reduce group size-related foraging efficiency. This is likely to be exacerbated by diminishing fish stocks due to resource competition and environmental change. PMID- 28989786 TI - Inferring individual-level processes from population-level patterns in cultural evolution. AB - Our species is characterized by a great degree of cultural variation, both within and between populations. Understanding how group-level patterns of culture emerge from individual-level behaviour is a long-standing question in the biological and social sciences. We develop a simulation model capturing demographic and cultural dynamics relevant to human cultural evolution, focusing on the interface between population-level patterns and individual-level processes. The model tracks the distribution of variants of cultural traits across individuals in a population over time, conditioned on different pathways for the transmission of information between individuals. From these data, we obtain theoretical expectations for a range of statistics commonly used to capture population-level characteristics (e.g. the degree of cultural diversity). Consistent with previous theoretical work, our results show that the patterns observed at the level of groups are rooted in the interplay between the transmission pathways and the age structure of the population. We also explore whether, and under what conditions, the different pathways can be distinguished based on their group-level signatures, in an effort to establish theoretical limits to inference. Our results show that the temporal dynamic of cultural change over time retains a stronger signature than the cultural composition of the population at a specific point in time. Overall, the results suggest a shift in focus from identifying the one individual-level process that likely produced the observed data to excluding those that likely did not. We conclude by discussing the implications for empirical studies of human cultural evolution. PMID- 28989787 TI - Interaction between path integration and visual orientation during the homing run of fiddler crabs. AB - Foraging fiddler crabs form a strict spatial relationship between their current positions and burrows, allowing them to run directly back to their burrows when startled even without visual contacts. Path integration (PI), the underlying mechanism, is a universal navigation strategy through which animals continuously integrate directions and distances of their movements. However, we report that fiddler crabs also use visual orientation during homing runs using burrow entrances as cues, with the prioritised mechanism (i.e. PI or visual) determined by the distance (which has a threshold value) between the goal, indicated by PI, and the visual cue. When we imposed homing errors using fake entrances (visual cue) and masking their true burrows (goal of PI), we found that frightened fiddler crabs initially ran towards the true burrow following PI, then altered their behaviour depending on the distance between the fake entrance and masked true burrow: if the distance was large, they kept running until they reached the true burrow, ignoring the visual cue; however, if the distance was small, they altered the homing path and ran until they reached the fake entrance. This suggests that PI and visual mechanism in fiddler crabs are mutually mediated to achieve their homing behaviour. PMID- 28989788 TI - Caching for where and what: evidence for a mnemonic strategy in a scatter hoarder. AB - Scatter-hoarding animals face the task of maximizing retrieval of their scattered food caches while minimizing loss to pilferers. This demand should select for mnemonics, such as chunking, i.e. a hierarchical cognitive representation that is known to improve recall. Spatial chunking, where caches with the same type of content are related to each other in physical location and memory, would be one such mechanism. Here we tested the hypothesis that scatter-hoarding eastern fox squirrels (Sciurus niger) are organizing their caches in spatial patterns consistent with a chunking strategy. We presented 45 individual wild fox squirrels with a series of 16 nuts of four different species, either in runs of four of the same species or 16 nuts offered in a pseudorandom order. Squirrels either collected each nut from a different location or collected all nuts from a single location; we then mapped their subsequent cache distributions using GPS. The chunking hypothesis predicted that squirrels would spatially organize caches by nut species, regardless of presentation order. Our results instead demonstrated that squirrels spatially chunked their caches by nut species but only when caching food that was foraged from a single location. This first demonstration of spatial chunking in a scatter hoarder underscores the cognitive demand of scatter hoarding. PMID- 28989789 TI - Bi-logistic model for disease dynamics caused by Mycobacterium tuberculosis in Russia. AB - In this work, we explore epidemiological dynamics by the example of tuberculosis in Russian Federation. It has been shown that the epidemiological dynamics correlates linearly with the virulence of Mycobacterium tuberculosis during the period 1987-2012. To construct an appropriate model, we have analysed (using LogLet decomposition method) epidemiological World Health Organization (WHO) data (period 1980-2014) and obtained, as result of their integration, a curve approximated by a bi-logistic function. This fact allows a subdivision of the whole population into parts, each of them satisfies the Verhulst-like models with different constant virulences introduced into each subsystem separately. Such a subdivision could be interconnected with the heterogeneous structure of mycobacterial population that has a high ability of adaptation to the host and strong mutability. PMID- 28989790 TI - Mechanistic insights into molecular evolution of species-specific differential glycosaminoglycan binding surfaces in growth-related oncogene chemokines. AB - Chemokines are chemotactic cytokines involved in leucocyte trafficking to infected tissue. Growth-related oncogene (GRO) chemokines namely CXCL1, CXCL2 and CXCL3 are neutrophil activating chemokines sharing a conserved three-dimensional structure, but encompassing functional diversity due to gene duplication and evolutionary events. However, the evolutionary mechanisms including selection pressures involved in diversification of GRO genes have not yet been characterized. Here, we performed comprehensive evolutionary analysis of GRO genes among different mammalian species. Phylogenetic analysis illustrated a species-specific evolution pattern. Selection analysis evidenced that these genes have undergone concerted evolution. Seventeen positively selected sites were obtained, although the majority of the protein is under purifying selection. Interestingly, these positively selected sites are more concentrated on the C terminal/glycosaminoglycan (GAG) binding and dimerization segment compared to receptor binding domain. Substitution rate analysis confirmed the C-terminal domain of GRO genes as the highest substituted segment. Further, structural analysis established that the nucleotide alterations in the GAG binding domain are the source of surface charge modulation, thus generating the differential GAG binding surfaces and multiple binding sites as per evolutionary pressure, although the helical surface is primordial for GAG binding. Indeed, such variable electrostatic surfaces are crucial to regulate chemokine gradient formation during a host's defence against pathogens and also explain the significance of chemokine promiscuity. PMID- 28989791 TI - Sweepstake evolution revealed by population-genetic analysis of copy-number alterations in single genomes of breast cancer. AB - Single-cell sequencing is a promising technology that can address cancer cell evolution by identifying genetic alterations in individual cells. In a recent study, genome-wide DNA copy numbers of single cells were accurately quantified by single-cell sequencing in breast cancers. Phylogenetic-tree analysis revealed genetically distinct populations, each consisting of homogeneous cells. Bioinformatics methods based on population genetics should be further developed to quantitatively analyse the single-cell sequencing data. We developed a bioinformatics framework that was combined with molecular-evolution theories to analyse copy-number losses. This analysis revealed that most deletions in the breast cancers at the single-cell level were generated by simple stochastic processes. A non-standard type of coalescent theory, the multiple-merger coalescent model, aided by approximate Bayesian computation fit well with the data, allowing us to estimate the population-genetic parameters in addition to false-positive and false-negative rates. The estimated parameters suggest that the cancer cells underwent sweepstake evolution, where only one or very few parental cells produced a descendent cell population. We conclude that breast cancer cells successively substitute in a tumour mass, and the high reproduction of only a portion of cancer cells may confer high adaptability to this cancer. PMID- 28989792 TI - How tight are beetle hugs? Attachment in mating leaf beetles. AB - Similar to other leaf beetles, rosemary beetles Chrysolina americana exhibit a distinct sexual dimorphism in tarsal attachment setae. Setal discoid terminals occur only in males, and they have been previously associated with a long-term attachment to the female's back (elytra) during copulation and mate guarding. For the first time, we studied living males and females holding to female's elytra. Pull-off force measurements with a custom-made tribometer featuring a self aligning sample holder confirmed stronger attachment to female elytra compared with glass in both males and females; corresponding to 45 and 30 times the body weight, respectively. In line with previous studies, males generated significantly higher forces than females on convex elytra and flat glass, 1.2 times and 6.8 times, respectively. Convex substrates like elytra seem to improve the attachment ability of rosemary beetles, because they can hold more strongly due to favourable shear angles of legs, tarsi and adhesive setae. A self-aligning sample holder is found to be suitable for running force measurement tests with living biological samples. PMID- 28989793 TI - Correction to 'Effects of time pressure and time passage on face-matching accuracy'. AB - [This corrects the article DOI: 10.1098/rsos.170249.]. PMID- 28989795 TI - A comparison of multiple sclerosis disease activity after discontinuation of fingolimod and placebo. AB - BACKGROUND: Cases of higher-than-expected disease activity have been reported following fingolimod discontinuation. OBJECTIVE: The objective of this paper is to assess the risk of substantially higher-than-expected disease activity post study drug discontinuation (SDD) at the individual patient level using data from the Phase III, placebo-controlled FREEDOMS and FREEDOMS II trials. METHODS: Baseline gadolinium-enhancing T1-lesion volumes were used to statistically model the expected level of MRI disease activity post-SDD. Patients exceeding this level were classed as "MRI outliers." Patients with an unusually high increase in Expanded Disability Status Scale score, hospitalization for relapse, severe relapse, or relapse with incomplete recovery post-SDD were classed as "clinical outliers." RESULTS: In FREEDOMS, the number of MRI outliers post-SDD was 2/69 (2.9%), 1/65 (1.5%) and 7/83 (8.4%) for the placebo, fingolimod 0.5 mg, and fingolimod 1.25 mg groups, respectively. In FREEDOMS II, the corresponding numbers were 4/72 (5.6%), 6/79 (7.6%) and 3/73 (4.1%). The number of clinical outliers across both trials was low. No consistent evidence of placebo vs fingolimod, dose-related or inter-trial patterns was discernable. CONCLUSION: The low number of clinical and MRI outliers and lack of any discernible pattern within and between trials, including between placebo and fingolimod, argues against a systematic risk of higher-than-expected recurrence of disease activity following discontinuation of fingolimod. PMID- 28989794 TI - A marker of biological age explains individual variation in the strength of the adult stress response. AB - The acute stress response functions to prioritize behavioural and physiological processes that maximize survival in the face of immediate threat. There is variation between individuals in the strength of the adult stress response that is of interest in both evolutionary biology and medicine. Age is an established source of this variation-stress responsiveness diminishes with increasing age in a range of species-but unexplained variation remains. Since individuals of the same chronological age may differ markedly in their pace of biological ageing, we asked whether biological age-measured here via erythrocyte telomere length predicts variation in stress responsiveness in adult animals of the same chronological age. We studied two cohorts of European starlings in which we had previously manipulated the rate of biological ageing by experimentally altering the competition experienced by chicks in the fortnight following hatching. We predicted that individuals with greater developmental telomere attrition, and hence greater biological age, would show an attenuated corticosterone (CORT) response to an acute stressor when tested as adults. In both cohorts, we found that birds with greater developmental telomere attrition had lower peak CORT levels and a more negative change in CORT levels between 15 and 30 min following stress exposure. Our results, therefore, provide strong evidence that a measure of biological age explains individual variation in stress responsiveness: birds that were biologically older were less stress responsive. Our results provide a novel explanation for the phenomenon of developmental programming of the stress response: observed changes in stress physiology as a result of exposure to early life adversity may reflect changes in ageing. PMID- 28989797 TI - The Place of Identity Dissonance and Emotional Motivations in Bio-Cultural Models of Religious Experience: A Report from the 19th Century. AB - Durham University's 'Hearing the Voice' project involves a multi-disciplinary exploration of hallucinatory-type phenomena in an attempt to revaluate and reframe discussions of these experiences. As part of this project, contemporaneous religious experiences (supernatural voices and visions) in the United States from the first half of the nineteenth century have been analysed, shedding light on the value and applicability of contemporary bio-cultural models of religious experience for such historical cases. In particular, this essay outlines four historical cases, seeking to utilise and to refine four theoretical models, including anthropologist Tanya Luhrmann's 'absorption hypothesis', by returning to something like William James' concern with 'discordant personalities'. Ultimately, the paper argues that emphasis on the role of identity dissonance must not be omitted from the analytical tools applied to these nineteenth-century examples, and perhaps should be retained for any study of religious experience generally. PMID- 28989796 TI - Externally controllable glycan presentation on nanoparticle surfaces to modulate lectin recognition. AB - Nature dynamically controls carbohydrate expression on cells rather than static presentation. Here we report synthetic glycosylated nanoparticles that contain polymeric 'gates' to enable external control (via temperature changes) of glycan surface expression, as an alternative to enzymatic control in nature. This approach offers a new dynamic multivalent scaffold for glycan recognition. PMID- 28989799 TI - Laser-Fabricated Plasmonic Nanostructures for Surface-Enhanced Raman Spectroscopy of Bacteria Quorum Sensing Molecules. AB - We used a laser-directed fabrication to create silver nanostructures on glass cover slips via photo-reduction. The resulting silver films exhibited plasmonic properties which show promise in application towards surface enhanced Raman spectroscopy (SERS). The enhancement factor calculated for the deposits was approximately ~106 using the standard thiophenol, which is comparable to other SERS-active plasmonic nanostructures fabricated through more complex techniques, such as electron beam lithography. The silver nanostructures were then employed in the enhancement of Raman signals from N-butyryl-L-homoserine lactone, a signaling molecule relevant to bacteria quorum sensing. In particular, the work presented here shows that the laser-deposited plasmonic nanostructures are promising candidates for monitoring concentrations of signaling molecules within biofilms containing quorum sensing bacteria. PMID- 28989798 TI - How to train radiology residents to diagnose pulmonary embolism using a dedicated MRI protocol. AB - BACKGROUND: In recent years, magnetic resonance imaging (MRI) has been suggested as an alternative to computed tomography angiography (CTA) to diagnose pulmonary embolism (PE). In previous studies, only senior radiologists have been evaluated as reviewers. PURPOSE: To investigate if radiology residents can be trained to review MRI regarding PE and to determine the learning curve effects. MATERIAL AND METHODS: Four residents independently went through a training program consisting of 70 participants that had undergone steady-state free precession MRI. The individuals were randomized into ten training sessions. For each exam, the review time and presence or absence of embolus was recorded. After completing each session, the residents received feedback on diagnostic accuracy compared to a consensus reading by two specialists. The residents were also presented with the corresponding CTA. RESULTS: The review time was nearly halved (P = 0.0002) during the training program. Comparing the first three sessions with the last three sessions for all residents, the review time decreased from 5:22 min to 2:51 min. The inter-reader agreement improved for all residents during the training program reaching a clinically acceptable level after seven sessions. CONCLUSION: Our study suggests that radiology residents can be trained to independently review MRI investigations regarding PE within a short training program. Similar training programs could be more extensively used as effective teaching method for residents. PMID- 28989800 TI - Opening already occluded middle cerebral artery, internal carotid artery or other cerebral arteries: when, where, how and why? PMID- 28989801 TI - Blood pressure gradients in cerebral arteries: a clue to pathogenesis of cerebral small vessel disease. AB - RATIONALE: The role of hypertension in cerebral small vessel disease is poorly understood. At the base of the brain (the 'vascular centrencephalon'), short straight arteries transmit blood pressure directly to small resistance vessels; the cerebral convexity is supplied by long arteries with many branches, resulting in a drop in blood pressure. Hypertensive small vessel disease (lipohyalinosis) causes the classically described lacunar infarctions at the base of the brain; however, periventricular white matter intensities (WMIs) seen on MRI and WMI in subcortical areas over the convexity, which are often also called 'lacunes', probably have different aetiologies. OBJECTIVES: We studied pressure gradients from proximal to distal regions of the cerebral vasculature by mathematical modelling. METHODS AND RESULTS: Blood flow/pressure equations were solved in an Anatomically Detailed Arterial Network (ADAN) model, considering a normotensive and a hypertensive case. Model parameters were suitably modified to account for structural changes in arterial vessels in the hypertensive scenario. Computations predict a marked drop in blood pressure from large and medium-sized cerebral vessels to cerebral peripheral beds. When blood pressure in the brachial artery is 192/113 mm Hg, the pressure in the small arterioles of the posterior parietal artery bed would be only 117/68 mm Hg. In the normotensive case, with blood pressure in the brachial artery of 117/75 mm Hg, the pressure in small parietal arterioles would be only 59/38 mm Hg. CONCLUSION: These findings have important implications for understanding small vessel disease. The marked pressure gradient across cerebral arteries should be taken into account when evaluating the pathogenesis of small WMIs on MRI. Hypertensive small vessel disease, affecting the arterioles at the base of the brain should be distinguished from small vessel disease in subcortical regions of the convexity and venous disease in the periventricular white matter. PMID- 28989802 TI - Clopidogrel loading dose versus maintenance dose to treat patients with acute ischaemic stroke in China (CLASS-China): results from a prospective double-blind randomised clinical trial. AB - AIM: The role of clopidogrel in treating patients with acute ischaemic stroke is unclear. We have conducted the clinical trial in order to evaluate the efficacy and safety of clopidogrel with a loading dose in treating patients with non cardiogenic acute ischaemic stroke. METHOD: Clopidogrel loading dose versus maintenance dose to treat patients with acute ischaemic stroke in China (CLASS China) was a prospective, randomised, double-blind and placebo-controlled clinical trial in China. Patients with acute ischaemic stroke of non-cardiogenic origin within 48 hours of onset were enrolled and those received thrombolysis were excluded. Enrolled patients were divided into two treatment groups: loading dose and routine dose. The primary outcome was the incidence of stroke recurrence or progression within 7 days. Primary safety outcome was measured by life threatening haemorrhage. An intent-to-treat analysis was used for the statistical analysis. RESULTS: From March 2008 to March 2010, a total of 303 patients from 16 centres were recruited into this study; six were excluded because of lack of basic information. Since the enrolment was slow and the study drug expired in March 2010, this clinical trial was stopped earlier than planned. No significant baseline and demographic differences were seen between the two groups. There was no difference in primary outcome between the loading dosage group 16.1% (24/149) and control group 14.9% (22/148), respectively (p=0.782). The mortality and disability rate within 90 days in loading dose group (19.6%) was slightly lower than that in controlled group (23.4%), p=0.444. Loading dose group had two (1.3%) cases of fatal haemorrhage and control group had four (2.7%) within 90 days, p=0.674. No significant difference was detected in other adverse events between the groups. CONCLUSION: In our study stopped early due to slow enrolment, loading dose of clopidogrel does not reduce the risk of recurrent stroke. Future trials with sufficient number of patients enrolled are needed to re-examine this hypothesis. PMID- 28989803 TI - Trend of declining stroke mortality in China: reasons and analysis. AB - INTRODUCTION: There is a downward trend of stroke-related mortality in the USA. By reviewing all published articles on stroke mortality in China, we analysed its trend and possible factors that have influenced the trend. METHODS: Both English and Chinese literatures were searched on the mortality of stroke or cerebrovascular diseases in China. Potential papers related to this topic were identified from PubMed, Medline, Embase, Cochrane Library, Wanfang Database, SINOMED and China National Knowledge Infrastructure databases. RESULTS: Comparing the results from the most recent population-based epidemiological survey and databank from the national Center for Disease Control and Prevention, the age adjusted stroke mortality rate has shown a downward trend among both urban and rural population in the past 30 years in China. Comparing with 30 years ago, the rate of stroke mortality has decreased by more than 31% in urban/suburban population and 11% in rural population. In men, the age-adjusted stroke mortality rate decreased by 18.9% and in women by 24.9% between 1994 and 2013. Factors that may have contributed to the trend of decreased stroke mortality rate include (1) improved healthcare coverage and healthcare environment; (2) improved treatment options and medical technology; (3) support by government to educate the public on stroke and stroke prevention; and (4) improved public knowledge on stroke. CONCLUSIONS: The age-adjusted stroke mortality rate in China has shown a downward trend among both urban and rural population in the past 30 years. The major influencing factors that helped in reducing stroke mortality in China included improved healthcare coverage, healthcare environment, the updated treatment options and modern medical technology. PMID- 28989806 TI - The progress of telestroke in China. AB - Stroke remains the leading cause of death in China. The disparity of distribution in specialists and hospitals affects access to timely stroke care. Telestroke, the use of telemedicine for stroke, may be the solution to access to stroke care. Telestroke can improve the rate of successful intravenous thrombolysis and shorten the time to treatment. Here we review the progress of telestroke in China. PMID- 28989805 TI - Migraine and stroke. AB - Migraines are generally considered a relatively benign neurological condition. However, research has shown an association between migraines and stroke, and especially between migraine with aura and ischaemic stroke. Patients can also suffer from migrainous infarction, a subset of ischaemic stroke that often occurs in the posterior circulation of younger women. The exact pathogenesis of migrainous infarct is not known, but it is theorised that the duration and local neuronal energy level from cortical spreading depression may be a key factor. Other factors contributing to migrainous infarct may include vascular, inflammatory, endothelial structure, patent foramen ovale, gender, oral contraceptive pill use and smoking. Vasoconstrictors such as the triptan and ergot class are commonly used to treat migraines and may also play a role. Migraine is also shown to be correlated to haemorrhagic stroke, although studies do not demonstrate causation versus association, and further studies are warranted. There are also some rare genetic diseases such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, retinal vasculopathy with cerebral leukodystrophy and others, which can cause both migraines and infarcts. On imaging, many migraineurs are found to have white matter changes similar to those seen in patients with stroke. These may be caused in part by alterations in resting cerebral blood flow and vasoconstrictor use. In treating patients with migraines, it is important to identify and modify any vascular risk factors such as hypertension, smoking, oral contraceptive pill use and lifestyle factors. Further studies will determine if more aggressive treatment of migraines can ultimately lead to fewer strokes in this population. PMID- 28989804 TI - The Chinese Stroke Association scientific statement: intravenous thrombolysis in acute ischaemic stroke. AB - The most effective medical treatment for acute ischaemic stroke (AIS) is to offer intravenous thrombolysis during the ultra-early period of time after the onset. Even based on the Consensus of Chinese Experts on Intravenous Thrombolysis for AIS in 2012 and 2014 Chinese Guidelines on the Diagnosis and Treatment of AIS, the rate of thrombolysis for AIS in China remained around 2.4%, and the rate of intravenous tissue plasminogen activator usage was only about 1.6% in real world. The indication of thrombolysis for AIS has been expanded, and contraindications have been reduced with recently published studies. In order to facilitate the standardisation of treating AIS, improve the rate of thrombolysis and benefit patients who had a stroke, Chinese Stroke Association has organised and developed this scientific statement. PMID- 28989807 TI - Red blood cell distribution width and ischaemic stroke. AB - The red blood cell distribution width (RDW) is a measure of red blood cell (RBC) size heterogeneity, which is easily calculated by dividing the SD of erythrocyte volumes for the mean corpuscular volume. Recent reporter suggested that, besides haematological diseases and anaemia, many human disorders may be closely associated with the elevated RDW. A literature review has revealed the RDW may be closely related to the development of ischaemic stroke, carotid artery atherosclerosis and cerebral embolism. Higher RDW could independently predict adverse outcomes in patients in these conditions. PMID- 28989808 TI - A Multi-Compartment Hybrid Computational Model Predicts Key Roles for Dendritic Cells in Tuberculosis Infection. AB - : Tuberculosis (TB) is a world-wide health problem with approximately 2 billion people infected with Mycobacterium tuberculosis (Mtb, the causative bacterium of TB). The pathologic hallmark of Mtb infection in humans and Non-Human Primates (NHPs) is the formation of spherical structures, primarily in lungs, called granulomas. Infection occurs after inhalation of bacteria into lungs, where resident antigen-presenting cells (APCs), take up bacteria and initiate the immune response to Mtb infection. APCs traffic from the site of infection (lung) to lung-draining lymph nodes (LNs) where they prime T cells to recognize Mtb. These T cells, circulating back through blood, migrate back to lungs to perform their immune effector functions. We have previously developed a hybrid agent based model (ABM, labeled GranSim) describing in silico immune cell, bacterial (Mtb) and molecular behaviors during tuberculosis infection and recently linked that model to operate across three physiological compartments: lung (infection site where granulomas form), lung draining lymph node (LN, site of generation of adaptive immunity) and blood (a measurable compartment). Granuloma formation and function is captured by a spatio-temporal model (i.e., ABM), while LN and blood compartments represent temporal dynamics of the whole body in response to infection and are captured with ordinary differential equations (ODEs). In order to have a more mechanistic representation of APC trafficking from the lung to the lymph node, and to better capture antigen presentation in a draining LN, this current study incorporates the role of dendritic cells (DCs) in a computational fashion into GranSim. RESULTS: The model was calibrated using experimental data from the lungs and blood of NHPs. The addition of DCs allowed us to investigate in greater detail mechanisms of recruitment, trafficking and antigen presentation and their role in tuberculosis infection. CONCLUSION: The main conclusion of this study is that early events after Mtb infection are critical to establishing a timely and effective response. Manipulating CD8+ and CD4+ T cell proliferation rates, as well as DC migration early on during infection can determine the difference between bacterial clearance vs. uncontrolled bacterial growth and dissemination. PMID- 28989810 TI - Carbon Support Surface Effects in the Gold-Catalyzed Oxidation of 5 Hydroxymethylfurfural. AB - Oxidation of 5-hydroxymethylfurfural into 2,5-furandicarboxylic acid is an important transformation for the production of bio-based polymers. Carbon supported gold catalysts hold great promise for this transformation. Here we demonstrate that the activity, selectivity, and stability of the carbon-supported gold nanoparticles in the oxidation of 5-hydroxymethylfurfural strongly depend on the surface properties of the carbon support. Gold nanoparticles supported on basic carbon materials with a low density of functional groups demonstrate higher activity in 5-hydroxymethylfurfural oxidation (TOFAu up to 1195 h-1), higher selectivity to 2,5-furandicarboxylic acid, and better stability in comparison to gold nanoparticles supported on carbon materials with acidic surface groups. Surface groups of basic carbon supports that are positively charged under the reaction conditions result in a higher adsorption and local concentration of hydroxyl ions, which act as cocatalysts for gold and enhance gold-catalyzed dehydrogenation. Negatively charged surface groups of acidic carbons repel hydroxyls and the intermediate monoacid anions, which leads to lower reaction rates and a high selectivity toward 2,5-hydroxymethylfurancarboxylic acid. Understanding the role of support surface charge and local hydroxyl anion concentration provides a basis for the rational design of the optimal carbon support surface chemistry for highly active, selective, and stable catalysts for the oxidation of 5-hydroxymethylfurfural and related reactions. PMID- 28989809 TI - Understanding Flavin-Dependent Halogenase Reactivity via Substrate Activity Profiling. AB - The activity of four native FDHs and four engineered FDH variants on 93 low molecular weight arenes was used to generate FDH substrate activity profiles. These profiles provided insights into how substrate class, functional group substitution, electronic activation, and binding impact FDH activity and selectivity. The enzymes studied could halogenate a far greater range of substrates than previously recognized, but significant differences in their substrate specificity and selectivity were observed. Trends between the electronic activation of each site on a substrate and halogenation conversion at that site were established, and these data, combined with docking simulations, suggest that substrate binding can override electronic activation even on compounds differing appreciably from native substrates. These findings provide a useful framework for understanding and exploiting FDH reactivity for organic synthesis. PMID- 28989811 TI - Metabolic Profiling of Green Tea Treatments in Zucker Diabetic Rats Using 1H NMR. AB - This study has investigated the metabolic effects of catechin-rich green tea (GT) and its formulation with ascorbic acid (AA) on the Zucker rat model of type 2 diabetes. AA is used to protect the GT catechins during digestion and increase bioavailability. Thirty two Zucker diabetic fatty (ZDF) rats were randomly divided into four groups (n=8 in each group) and treated with water, GT, AA and GT+AA respectively for five weeks. Urinary metabolic profiles were determined using 1H NMR spectroscopy. Fourteen metabolites were identified and their 24-hr excretions were quantified. Changes in the 14 metabolites demonstrated differential treatment effects on the metabolism of ZDF rats. GT and AA were found to be able to independently reduce urinary excretions of most metabolites that were over-excreted in the control diabetic rats, such as oxidative stress marker metabolites and TCA cycle metabolites. GT showed a great potential in controlling metabolic acidosis by suppressing the excretion of lactic acid and acetic acid from diabetic rats and GT+AA showed a remarkably stronger suppression than GT while AA was unable to suppress these two acids. Further investigation is needed to better understand the role of GT and/or formulated GT in altering the metabolic pathways in the diabetic animal model as well as in humans. PMID- 28989812 TI - Sparse Canonical Correlation Analysis via Truncated l1-norm with Application to Brain Imaging Genetics. AB - Discovering bi-multivariate associations between genetic markers and neuroimaging quantitative traits is a major task in brain imaging genetics. Sparse Canonical Correlation Analysis (SCCA) is a popular technique in this area for its powerful capability in identifying bi-multivariate relationships coupled with feature selection. The existing SCCA methods impose either the l1-norm or its variants. The l0-norm is more desirable, which however remains unexplored since the l0-norm minimization is NP-hard. In this paper, we impose the truncated l1-norm to improve the performance of the l1-norm based SCCA methods. Besides, we propose two efficient optimization algorithms and prove their convergence. The experimental results, compared with two benchmark methods, show that our method identifies better and meaningful canonical loading patterns in both simulated and real imaging genetic analyse. PMID- 28989813 TI - A brush-polymer conjugate of exendin-4 reduces blood glucose for up to five days and eliminates poly(ethylene glycol) antigenicity. AB - The delivery of therapeutic peptides and proteins is often challenged by a short half-life, and thus the need for frequent injections that limit efficacy, reduce patient compliance and increase treatment cost. Here, we demonstrate that a single subcutaneous injection of site-specific (C-terminal) conjugates of exendin 4 (exendin) - a therapeutic peptide that is clinically used to treat type 2 diabetes - and poly[oligo(ethylene glycol) methyl ether methacrylate] (POEGMA) with precisely controlled molecular weights lowered blood glucose for up to 120 h in fed mice. Most notably, we show that an exendin-C-POEGMA conjugate with an average of 9 side-chain ethylene glycol (EG) repeats exhibits significantly lower reactivity towards patient-derived anti-poly(ethylene glycol) (PEG) antibodies than two FDA-approved PEGylated drugs, and that reducing the side-chain length to 3 EG repeats completely eliminates PEG antigenicity without compromising in vivo efficacy. Our findings establish the site-specific conjugation of POEGMA as a next-generation PEGylation technology for improving the pharmacological performance of traditional PEGylated drugs, whose safety and efficacy are hindered by pre-existing anti-PEG antibodies in patients. PMID- 28989815 TI - Microinjection of Ghrelin into the Ventral Tegmental Area Potentiates Cocaine Induced Conditioned Place Preference. AB - Prior work has shown that systemic cocaine pretreatment augments cocaine conditioned place preference (CPP) in rats. In contrast, ghrelin receptor antagonism attenuates cocaine and amphetamine-induced CPP. In order to further investigate ghrelin's role in dopamine-mediated reward, the present report examined whether pretreament with ghrelin, administered directly into the ventral tegmental area (VTA) of the midbrain, would potentiate the rewarding properties of cocaine as measured by CPP. Adult male Sprague-Dawley rats were given access to either side of the CPP chamber in order to determine initial side preferences. The rats were then restricted to either their non-preferred or preferred side over the course of conditioning which lasted for a total of 16 consecutive days. This was followed by a final test day to then reassess preference. On days where rats were confined to their non-preferred side, ghrelin (30 - 300 pmol) and cocaine (0.625 - 10 mg/kg IP) were administered immediately prior to the conditioning trial. On alternate days rats were treated with vehicle and placed into what was initially determined to be their preferred side. CPP was calculated as the difference in percentage of total time spent in the treatment-paired compartment during the post-conditioning session and the pre-conditioning session. Our results indicated that both cocaine and ghrelin elicited CPP and that ghrelin pre-treatment potentiated the effect of cocaine on place preference. Overall, these findings provide additional support for the argument that ghrelin signaling within the VTA enhances the rewarding effects of psychostimulant compounds. PMID- 28989814 TI - Engineering the pre-metastatic niche. AB - The pre-metastatic niche - the accumulation of aberrant immune cells and extracellular matrix proteins in target organs - primes the initially healthy organ microenvironment and renders it amenable for subsequent metastatic cell colonization. By attracting metastatic cancer cells, mimics of the pre-metastatic niche offer both diagnostic and therapeutic potential. However, deconstructing the complexity of the niche by identifying the interactions between cell populations and the mediatory roles of the immune system, soluble factors, extracellular matrix proteins, and stromal cells has proved challenging. Experimental models need to recapitulate niche-population biology in situ and mediate in vivo tumour-cell homing, colonization and proliferation. In this Review, we outline the biology of the pre-metastatic niche and discuss advances in engineered niche-mimicking biomaterials that regulate the behaviour of tumour cells at an implant site. Such oncomaterials offer strategies for early detection of metastatic events, inhibiting the formation of the pre-metastatic niche, and attenuating metastatic progression. PMID- 28989816 TI - Social Determinants of Health Associated with HBV Testing and Access to Care among Foreign-born Persons Residing in the United States: 2009 - 2012. AB - OBJECTIVES: To describe how select Social Determinants of Health (SDH) are associated with the burden of hepatitis B virus (HBV) infection among foreign born persons residing in the United States. METHODS: Multivariate logistic regression was used to examine the Racial and Ethnic Approaches to Community Health (REACH) 2010 Risk Factor Survey data to investigate the independent relationship between SDH and HBV testing and access to care. RESULTS: HBV infected persons with insurance were more likely to see a physician than those without. Respondents worried about money to pay rent or mortgage were more likely to report HBV infection than individuals who reported they never worry. Compared to English speakers, Spanish-speakers were less likely to report HBV infection, Vietnamese-speakers were more likely to see a physician for HBV infection, and Khmer-speakers were less likely to be tested. CONCLUSIONS: Health insurance coverage, worries about paying rent, and language of interview all differentially affect HBV testing and linkages to care among foreign-born persons. Multi sectorial stakeholder collaborative efforts should integrate resources to provide culturally sensitive health promotion campaigns which may improve HBV related outcomes. PMID- 28989817 TI - Medical and Surgical Advancements in the Management of Cystic Fibrosis Chronic Rhinosinusitis. AB - PURPOSE OF REVIEW: The purpose of this review is to provide otolaryngologists with the most up-to-date advancements in both the medical and surgical management of CF-related sinus disease. RECENT FINDINGS: Recent studies have supported more aggressive CRS management, often with a combination of both medical and surgical therapies. Comprehensive treatment strategies have been shown to reduce hospital admissions secondary to pulmonary exacerbations in addition to improving CRS symptoms. Still, current management strategies are lacking in both high-level evidence and standardized guidelines. SUMMARY: The unified airway model describes the bi-directional relationship between the upper and lower airways as a single functional unit and suggests that CRS may play a pivotal role in both the development and progression of lower airway disease. Current strategies for CF CRS focus primarily on amelioration of symptoms with antibiotics, nasal saline and/or topical medicated irrigations, and surgery. However, there are no definitive management guidelines and there remains a persistent need for additional studies. Nevertheless, otolaryngologists have a significant role in the overall management of CF, which requires a multi-disciplinary approach and a combination of both surgical and medical interventions for optimal outcomes of airway disease. Here we present a review of currently available literature and summarize medical and surgical therapies best suited for the management of CF related sinus disease. PMID- 28989819 TI - Skeletal Muscle CAP Expression Increases after Dietary Restriction and Aerobic Training in Women with a History of Gestational Diabetes. AB - The purpose is to determine the effects of 6 months caloric restriction and aerobic training (3x/wk) (CR+AEX) on c-CBL associated protein (CAP) gene expression in women with a history of GDM. CAP is involved in cell signaling and protein ubiquitination, and is linked to the development of insulin resistance. Obese (BMI=32 +/- 1 kg/m2, % fat=46 +/- 2, X +/- SEM), sedentary (VO2 max=21.2 +/ 1.2 ml/kg/min), women aged 52 +/- 2 years participated in 6 months D+WL (n=10) with body composition, fitness (VO2 max), and glucose tolerance testing. Insulin sensitivity was assessed during the last 30 min of 2-hour hyperinsulinemic euglycemic clamps (40 mU.m-2.min-1) pre and post interventions. Vastus lateralis skeletal muscle biopsies (n=7) were conducted and CAP, GLUT4 and glycogen synthase (GS) gene expression measured by RT-PCR. No change in FFM by DXA was observed, but body weight decreased 8% with losses of total body fat mass (P<0.05) and a 10% increase in VO2 max (P<0.01). Glucose and insulin areas under the curve by OGTT decreased (P<0.05). Glucose utilization during the clamp increased 27% (23.1 +/- 3.8 vs. 29.4 +/- 3.6 umol.kg.min-1, P<0.05). Vastus lateralis skeletal muscle CAP expression increased 21% (P<0.05) but GLUT4 did not. Results suggest that changes in CAP could be involved in the improvement in glucose metabolism with caloric restriction and aerobic training in women with a history of gestational diabetes. PMID- 28989818 TI - Larger Receptive Field Size as a Mechanism Underlying Atypical Motion Perception in Autism Spectrum Disorder. AB - Atypical visual motion perception has been widely observed in individuals with autism spectrum disorder (ASD). The pattern of results, however, has been inconsistent. Emerging mechanistic hypotheses seek to explain these variable patterns of atypical motion sensitivity, each uniquely predicting specific patterns of performance across varying stimulus conditions. Here, we investigated the integrity of two such fundamental mechanisms-response gain control and receptive field size. Twenty children and adolescents with ASD and 20 typically developing (TD) age- and IQ-matched controls performed a motion discrimination task. To adequately model group differences in both mechanisms of interest, we tested a range of 23 stimulus conditions varying in size and contrast. Results revealed a motion perception impairment in ASD that was specific to the smallest sized stimuli (1 degrees ), irrespective of stimulus contrast. Model analyses provided evidence for larger receptive field size in ASD as the mechanism that explains this size-specific reduction of motion sensitivity. PMID- 28989820 TI - Characterization of 31 microsatellite markers for Sinocalycanthus chinensis (Calycanthaceae), an endemic endangered species. AB - PREMISE OF THE STUDY: Thirty-one microsatellite markers were developed for Sinocalycanthus chinensis (Calycanthaceae), an endemic endangered species in China. METHODS AND RESULTS: Twenty-one polymorphic and 10 monomorphic microsatellite markers of S. chinensis were developed using methods of biotin streptavidin capture and capillary electrophoresis. The number of alleles per locus was one to 20 with an average of 4.677 in 90 individuals taken from two populations in Zhejiang Province and one population in Anhui Province in China. Mean observed and expected heterozygosity across all three populations were 0.403 +/- 0.061 (0.033-1.000 per locus) and 0.510 +/- 0.043 (0.032-0.797 per locus), respectively. Of these 31 loci, 29 were successfully amplified in Calycanthus floridus. CONCLUSIONS: These microsatellite markers will be useful for studies of population genetic diversity and phylogeny of S. chinensis and C. floridus. PMID- 28989821 TI - Primers for Castilleja and their utility across Orobanchaceae: I. Chloroplast primers. AB - PREMISE OF THE STUDY: Chloroplast primers were developed from genomic data for the taxonomically challenging genus Castilleja. We further tested the broader utility of these primers across Orobanchaceae, identifying a core set of chloroplast primers amplifying across the clade. METHODS AND RESULTS: Using a combination of three low-coverage Castilleja genomes and sequence data from 12 Castilleja plastomes, 76 primer combinations were specifically designed and tested for Castilleja. The primers targeted the most variable portions of the plastome and were validated for their applicability across the clade. Of these, 38 primer combinations were subsequently evaluated in silico and then validated across other major clades in Orobanchaceae. CONCLUSIONS: These results demonstrate the utility of these primers, not only across Castilleja, but for other clades in Orobanchaceae-particularly hemiparasitic lineages-and will contribute to future phylogenetic studies of this important clade of parasitic plants. PMID- 28989822 TI - Primers for Castilleja and their utility across Orobanchaceae: II. Single-copy nuclear loci. AB - PREMISE OF THE STUDY: We developed primers targeting nuclear loci in Castilleja with the goal of reconstructing the evolutionary history of this challenging clade. These primers were tested across other major clades in Orobanchaceae to assess their broader utility. METHODS AND RESULTS: We assembled low-coverage genomes for three taxa in Castilleja and developed primer combinations for the single-copy conserved ortholog set (COSII) and the pentatricopeptide repeat (PPR) gene family. These primer combinations were designed to take advantage of the Fluidigm microfluidic PCR platform and are well suited for high-throughput sequencing applications. Eighty-seven primers were designed for Castilleja, and 27 were found to have broader utility in Orobanchaceae. CONCLUSIONS: These results demonstrate the utility of these primers, not only across Castilleja, but for other lineages within Orobanchaceae as well. This expanded molecular toolkit will be an asset to future phylogenetic studies in Castilleja and throughout Orobanchaceae. PMID- 28989823 TI - Isolation of polymorphic microsatellite loci in the New Zealand endemic sand binder, Ficinia spiralis (Cyperaceae). AB - PREMISE OF THE STUDY: Ficinia spiralis (Cyperaceae) is a declining sand-binding sedge of ecological and cultural importance. Microsatellite primers were developed in F. spiralis to investigate how population genetic structure is related to the pronounced morphological, physiological, and ecological variation observed in this species. METHODS AND RESULTS: A 454 shotgun-sequencing approach was used to generate 157,274 raw sequence reads, 536 of which contained microsatellites. After initial primer testing for 40 loci, 14 polymorphic loci were isolated, containing five to 27 alleles per locus. Ten of these loci also amplified in a congener, F. nodosa. CONCLUSIONS: These loci will enable the assessment of the population genetic structure of F. spiralis, improving our understanding of the population processes underlying the observed morphological, physiological, and ecological variation in this endemic species. As the first microsatellites developed in Ficinia, these loci are a valuable resource for population genetic studies within this genus. PMID- 28989824 TI - Development of single-copy nuclear intron markers for species-level phylogenetics: Case study with Paullinieae (Sapindaceae). AB - PREMISE OF THE STUDY: We developed a bioinformatic pipeline that leverages a publicly available genome and published transcriptomes to design primers in conserved coding sequences flanking targeted introns of single-copy nuclear loci. Paullinieae (Sapindaceae) is used to demonstrate the pipeline. METHODS AND RESULTS: Transcriptome reads phylogenetically closer to the lineage of interest are aligned to the closest genome. Single-nucleotide polymorphisms are called, generating a "pseudoreference" closer to the lineage of interest. Several filters are applied to meet the criteria of single-copy nuclear loci with introns of a desired size. Primers are designed in conserved coding sequences flanking introns. Using this pipeline, we developed nine single-copy nuclear intron markers for Paullinieae. CONCLUSIONS: This pipeline is highly flexible and can be used for any group with available genomic and transcriptomic resources. This pipeline led to the development of nine variable markers for phylogenetic study without generating sequence data de novo. PMID- 28989825 TI - Fungus-specific SSR markers in the Antarctic lichens Usnea antarctica and U. aurantiacoatra (Parmeliaceae, Ascomycota). AB - PREMISE OF THE STUDY: Usnea antarctica and U. aurantiacoatra (Parmeliaceae) are common lichens in the maritime Antarctic. These species share the same habitats on King George Island (South Shetland Islands, Antarctica) and are distinguishable based on reproductive strategies. METHODS AND RESULTS: We developed 23 fungus-specific simple sequence repeat (SSR) markers that cross amplify between the two species. We used a low-coverage genome-skimming approach on one sample of each species to identify SSR repeats in the two species. Primers were designed for 3-4-bp repeats, and only the loci common to both species were selected for further analyses. Seventy-seven samples of the two species were selected to assess fungal specificity, genetic variability, and linkage of the markers. In addition, we tested cross-amplification in other Usnea species. CONCLUSIONS: The 23 newly designed SSR markers are suitable for population genetic and phylogeographic studies of Usnea species. PMID- 28989826 TI - Isolation and characterization of 30 microsatellite loci for Cunninghamia lanceolata (Taxodiaceae). AB - PREMISE OF THE STUDY: To quantify the population-level genetic characteristics of Cunninghamia lanceolata (Taxodiaceae), an important timber conifer, we developed 30 pairs of microsatellite primers based on the nuclear genome. METHODS AND RESULTS: Using the streptavidin-biotin capture system, we developed 14 polymorphic and 16 monomorphic microsatellites. Polymorphisms were detected in 14 loci using 94 individual trees that were collected from three C. lanceolata populations in Hubei and Zhejiang provinces and in Chongqing Municipality, China. There were three to 30 alleles per locus, and the observed and expected heterozygosities ranged from 0.0313-0.8333 and from 0.0313-0.9246, respectively. Cross-species amplification showed that two to seven polymorphic loci were functional in three of the five related species that were collected. CONCLUSIONS: Our newly developed microsatellite primers provide neutral molecular markers that are beneficial to future studies of population genetics and germplasm conservation of C. lanceolata. PMID- 28989827 TI - Recovery of Volatile Fatty Acids from Fermented Wastewater by Adsorption. AB - Separation of volatile fatty acids (VFAs) from fermented wastewater is challenging, due to low VFA concentrations in mineral-rich streams. As a result, separation capacity and selectivity with traditional solvents and adsorbents are both compromised. In this study, using a complex artificial model solution mimicking real fermented wastewaters, it is shown that a simple and robust adsorption-based separation technique can retain a remarkable capacity and selectivity for VFAs. Four types of polystyrene-divinylbenzene-based resins (primary, secondary, and tertiary amine-functionalized, and nonfunctionalized) were examined as the adsorbents. The presence of chloride, sulfate, and phosphate salts resulted in coadsorption of their acidic forms HCl, H2SO4, and H3PO4 on amine-functionalized adsorbents, and severely reduced the VFA capacity. With the nonfunctionalized adsorbent, almost no mineral acid coadsorption was observed. This together with a high total VFA capacity of up to 76 g/kg in equilibrium with the model solution containing a total VFA concentration of 1 wt % resulted in a very high selectivity for the VFAs. Nitrogen-stripping with various temperature profiles was applied to regenerate the adsorbent, and study the potential for fractionation of the VFAs during regeneration. Butyric acid (HBu) was obtained in mole fractions of up to 0.8 using a stepwise increase in the stripping temperature from 25 degrees C via 120 to 200 degrees C. During four successive adsorption-regeneration cycles, no reduction in the adsorption capacity was observed. PMID- 28989829 TI - Bony Hyperostosis Recurrence after Complete Resection of Sphenoorbital Meningioma. AB - Bony hyperostosis is commonly associated with meningioma growth and is considered one of the characteristic signs on imaging; however, recurrence of meningiomas in the sphenoorbital area, including associated hyperostosis, is typically precluded by gross total resection of the lesion. This 63-year-old man presented with progressive double vision and proptosis in the right eye. He underwent frontotemporal craniotomy and partial removal after magnetic resonance imaging demonstrated a right sphenoorbital meningioma extending to the orbit and middle fossa. He had transient improvement of his symptoms postoperatively but experienced a progressive recurrence of symptoms and new onset of right facial hypoesthesia in the distribution of V1 and V2. We performed a right frontotemporal craniotomy with removal of the nodular part, as well as extensive drilling. Although the postoperative computed tomography scan revealed a gross total resection, the five-year follow-up scan demonstrated a recurrent hyperostosis in the region of the lesser and greater sphenoid wings, the middle cranial fossa floor with inferior extension toward the infratemporal fossa, and the sphenoid sinus wall. After another redo surgery, the patient continues to be monitored with yearly imaging. The extent of surgical resection is one of the most important predictors of meningioma recurrence postoperatively, and cases of recurrence after gross total resection are rare. PMID- 28989828 TI - Magnetic Resonance Imaging of Primary Hepatic Malignancies in Patients With and Without Chronic Liver Disease: A Pictorial Review. AB - Primary hepatic malignancies are less common than metastatic diseases, but a recognition of these lesions is important for diagnosis and treatment planning. Magnetic resonance imaging (MRI) provides the most imaging information to diagnose lesions noninvasively and to narrow differential diagnoses. This paper reviews the imaging findings of chronic liver disease and primary hepatic malignancies, including hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (CCA), epithelioid hemangioendothelioma, hepatic angiosarcoma, and primary hepatic lymphoma. Clinical and MRI features are reviewed to improve the readers' recognition of these tumors, allowing for a narrower differential diagnosis when liver masses are encountered on abdominal imaging. PMID- 28989830 TI - Combining Magnetic Resonance Spectroscopy and Magnetic Resonance Imaging in Diagnosing Focal Brain Lesions in Children. AB - Introduction We attempted to find the sensitivity and specificity of various pediatric brain masses in the Pakistani population while keeping histopathology or clinical diagnosis as the gold standard. Methods This was a retrospective study that was conducted from January 2007 to January 2016. We reviewed the records of 204 patients that presented to the radiology department of Aga Khan University Hospital (AKUH). Out of the 204, 135 pediatric patients in the 0-18 age group with focal brain lesions who underwent magnetic resonance spectroscopy (MRS) and a biopsy or clinical diagnosis were included. If histopathology was available, it was taken as the gold standard test; otherwise, clinical diagnosis was considered the gold standard. Results We had a total of 135 patients, of which 71 (52.6%) were male and 64 (47.4%) were female. The mean age represented was 7.2 +/- 4.5 years with a range of 1-18 years. We found radiology (magnetic resonance imaging (MRI) and MRS) to have a 91.7% sensitivity and a 94.3% specificity for tumors. For leukodystrophy, there was a 64.3% sensitivity and a 97.3% specificity. On the other hand, infection and mitochondrial disorders had sensitivities of 35.7% and 21.7%, respectively, and specificities of 98.9% and 97.1%, respectively. The category labeled "others" had a sensitivity of 27.4% and a specificity of 86.0%. Conclusion A combination of MRI and MRS was highly sensitive and specific for tumors. For infections, leukodystrophy, mitochondrial disorders, and the category of "others," it was highly specific but poorly sensitive. PMID- 28989832 TI - Constraints to do realistic modeling of the electric field ahead of the tip of a lightning leader. AB - Several computer models exist to explain the observation of terrestrial gamma-ray flashes (TGFs). Some of these models estimate the electric field ahead of lightning leaders and its effects on electron acceleration and multiplication. In this paper, we derive a new set of constraints to do more realistic modeling. We determine initial conditions based on in situ measurements of electric field and vertical separation between the main charge layers of thunderclouds. A maximum electric field strength of 50 kV/cm at sea level is introduced as the upper constraint for the leader electric field. The threshold for electron avalanches to develop of 2.86 kV/cm at sea level is introduced as the lower value. With these constraints, we determine a region where acceleration and multiplication of electrons occur. The maximum potential difference in this region is found to be ~52 MV, and the corresponding number of avalanche multiplication lengths is ~3.5. We then quantify the effect of the ambient electric field compared to the leader field at the upper altitude of the negative tip. Finally, we argue that only leaders with the highest potential difference between its tips (~600 MV) can be candidates for the production of TGFs. However, with the assumptions we have used, these cannot explain the observed maximum energies of at least 40 MeV. Open questions with regard to the temporal development of the streamer zone and its effect on the shape of the electric field remain. PMID- 28989831 TI - Intraoperative Awareness and Recall: A Comparative Study of Dexmedetomidine and Propofol in Cardiac Surgery. AB - Background Awareness during general anesthesia is undesired and unanticipated patient wakefulness during surgery or recall of intraoperative events. Incidence of awareness in patients undergoing cardiac surgery is significantly higher than the overall incidence of 1% during general surgery. Awareness during cardiac surgery can be prevented by a number of methods. One such method is the supplemental, intraoperative use of sedative agents. Propofol, a bisubstituted phenol, is an intravenous general anesthetic that has been shown to reduce the incidence of awareness. Dexmedetomidine-an alpha2-adrenergic agonist with anxiolytic, opioid, and general anesthetic-sparing properties-is being considered for maintaining intraoperative depth of anesthesia. The purpose of this study was to evaluate the effect of dexmedetomidine on depth of anesthesia and to compare it with the effect of propofol in cardiac surgery. Methods This was a prospective, randomized, double-blind study conducted in a tertiary-care hospital. Sixty patients with American Society of Anesthesiologists (ASA) physical status I-III planned for elective open heart surgery were randomized into two groups of 30 patients each. Each patient of the dexmedetomidine group received an initial loading dose of dexmedetomidine at 1 mcg kg-1 over 10 minutes followed by infusion at the rate of 0.2-0.6 mcg kg-1 hr-1. Patients of the propofol group received propofol infusion at the rate of 0.25-1 mg kg-1 hr-1. An identical technique-of standard general anesthesia and routine physiological monitoring-was used in both groups. Bispectral scores were recorded at predetermined intervals during surgery and the target bispectral index (BIS) was kept at 50+/-10. The patients were assessed for awareness and recall 24 hours after tracheal extubation using the Brice Questionnaire. Results Intraoperative BIS scores remained within the target range in both groups; however, the BIS scores showed variable trends between the groups and were significantly lower in the dexmedetomidine group (p < 0.001). None of the patients in either group had recall of intraoperative events. Conclusion Administration of dexmedetomidine was as effective in reducing awareness and recall in cardiac surgery compared to propofol. Thus, dexmedetomidine can be used as an alternative sedative agent to prevent awareness and recall in cardiac surgery. PMID- 28989833 TI - Black Sea thermohaline properties: Long-term trends and variations. AB - The current knowledge about spatial and temporal dynamics of the Black Sea's thermohaline structure is incomplete because of missing data and sparse distribution of existing measurements in space and time. This study presents 56 year continuous simulations of the Black Sea's hydrodynamics using the 3D General Estuarine Transport Model (GETM), without incorporating any relaxation toward climatological or observational data fields. This property of the model allows us to estimate independent temporal trends, in addition to resolving the spatial structure. The simulations suggest that the intermediate layer temperature is characterized by a weak positive trend (warming), whereas the surface temperature does not show a clear linear trend. Different salinity trends have been established at the surface (negative), upper (weaker negative) and main halocline (positive). Three distinct dynamic periods are identified (1960-1970, 1970-1995, 1995-2015), which exhibit pronounced changes in the Black Sea's thermohaline properties and basin circulation. Strengthening of the main cyclonic circulation, accompanied by intensification of the mesoscale anticyclonic eddy formation is found. Both events strongly affect the sea surface salinity but contribute in opposing directions. Specifically, strong composite large-scale circulation leads to an increase in sea surface salinity, while enhanced formation of mesoscale anticyclones decreases it. Salinity evolution with time is thus the result of the competition of these two opposing yet interdependent processes. PMID- 28989834 TI - The change of picrotoxin-induced epileptiform discharges to the beta oscillation by carbachol in rat hippocampal slices. AB - The study aimed to determine whether and how the activation of the acetylcholine receptor affects epileptiform discharges in the CA3 region in a rat hippocampus. Picrotoxin (100 MUM), a GABAA receptor antagonist, was applied to a hippocampal slice to induce epileptiform discharges. The effects of the cholinergic agonist, carbachol, on the discharges were examined at the several concentrations (1-30 MUM). Carbachol had different impacts on epileptiform discharges at the different concentrations. Relatively low concentrations of carbachol (<10 MUM) increased the frequency but decreased the amplitude of the discharges. At 10 MUM, carbachol induced the discharges, including bursts of theta frequency oscillations. At 30 MUM, carbachol could induce bursts of beta frequency oscillations instead of epileptiform discharges. The amplitudes of the oscillations were smaller than those of the discharges. Carbachol suppressed the evoked population EPSPs (pEPSPs) in a dose-dependent manner. These effects were blocked by the muscarinic cholinergic receptor antagonist atropine sulfate. The high level of muscarinic receptor activation can replace epileptiform discharges with theta or beta oscillation. These results suggest that the dose-dependent alternation of the acetylcholine receptor activation may provide the three different stages the epileptiform discharges, the bursts of theta oscillation, and the bursts of the beta oscillation. PMID- 28989835 TI - Isn't there an inductance factor in the plasma membrane of nerves? AB - It is established knowledge that the action potential event of nerves is formed by the combination of a phasic inward Na+ current and a following outward K+ current which increases gradually. These changes in current are commonly referred to as conductance changes of channels for Na+ and K+ with time. On the other hand, electric requirements for action potential generation in phenomena such as anode break excitation, hyperpolarizing break stimulation and accommodation, strongly suggest an existence of an inductance factor in the plasma membrane of nerves. In this study, the possibility that the Na+ channel could be simulated by a circuit composed serially of resistance (R), inductance (L), and capacitance (C) was examined using a computer simulation. Electric responses of the RLC circuit (R2/4L2 >= 1/LC) to step voltages are as followings: (1) A transient potential is produced on the inductor, (2) the circuit current simulates well the Na+ current manner, and (3) time course of the capacitor potential resembles the K+ current change. PMID- 28989836 TI - The Ongoing Quest for the Holy Bone Graft Grail: Scientific Progress, Economic Bonanza, or Quixotic Quagmire? PMID- 28989837 TI - Trends, Costs, and Complications of Anterior Cervical Discectomy and Fusion With and Without Bone Morphogenetic Protein in the United States Medicare Population. AB - STUDY DESIGN: Retrospective database review. OBJECTIVES: After the Food and Drug Administration approved bone morphogenetic protein-2 (BMP) in 2002, BMP was used off-label in the cervical spine to increase bone growth and bony fusion. Since then, concerns have been raised regarding complication rates and safety. This study was conducted to examine the use of BMP in anterior cervical discectomy and fusion (ACDF) in the Medicare population and to determine risk of complications and associated costs within 90 days of surgery. METHODS: Patients who underwent ACDF were identified using Current Procedural Terminology (CPT) and International Classification of Diseases, Ninth Revision Procedure codes (ICD9-P). Complications were identified using ICD9 diagnostic codes. Charges were calculated as amount billed, and reimbursements were calculated as amounts paid by Medicare. Data for these analyses came from a nationwide claims database. RESULTS: A total of 215 047 patients were identified who had ACDF from 2005 to 2011. For the majority of the procedures (89.0%), BMP was not used. BMP use rose from 11.84% in 2005 to a peak of 16.73% in 2007 before decreasing to 12.01% in 2011. BMP was used 16% more in women than men. BMP use was the highest in the West (13.6%) followed by Midwest (11.8%), South (10.6%), and Northeast (7.5%). There was a higher overall complication rate in the BMP group (2.1%) compared with the non-BMP group (1.9%) (odds ratio [OR] = 1.11, 95% CI = 1.01-1.22). The BMP group also had a higher rate of wound complications (0.98% vs 0.76%, OR = 1.29, 95% CI = 1.12-1.48). In this study population, there was no difference in dysphagia/hoarseness, neurologic, medical, or other complications. During the 90 day perioperative period, BMP surgeries were charged at 17.6% higher than non-BMP surgeries. CONCLUSIONS: The use of BMP in ACDF in the Medicare population has decreased since a peak in 2007. The rate of wound and overall complications for BMP use with ACDF was higher than without. Our results regarding dysphagia/hoarseness did not show a statistically meaningful difference, which is in contrast with many other studies. Charges associated with BMP use were higher during the 90-day perioperative period. PMID- 28989838 TI - Sacral Fractures and Associated Injuries. AB - STUDY DESIGN: Literature review. OBJECTIVE: The aim of this review is to describe the injuries associated with sacral fractures and to analyze their impact on patient outcome. METHODS: A comprehensive narrative review of the literature was performed to identify the injuries associated with sacral fractures. RESULTS: Sacral fractures are uncommon injuries that result from high-energy trauma, and that, due to their rarity, are frequently underdiagnosed and mistreated. Only 5% of sacral fractures occur in isolation. Injuries most often associated with sacral fractures include neurologic injuries (present in up to 50% of sacral fractures), pelvic ring disruptions, hip and lumbar spine fractures, active pelvic/ abdominal bleeding and the presence of an open fracture or significant soft tissue injury. Diagnosis of pelvic ring fractures and fractures extending to the lumbar spine are key factors for the appropriate management of sacral fractures. Importantly, associated systemic (cranial, thoracic, and abdominopelvic) or musculoskeletal injuries should be promptly assessed and addressed. These associated injuries often dictate the management and eventual outcome of sacral fractures and, therefore, any treatment algorithm should take them into consideration. CONCLUSIONS: Sacral fractures are complex in nature and often associated with other often-missed injuries. This review summarizes the most relevant associated injuries in sacral fractures and discusses on their appropriate management. PMID- 28989839 TI - Use of Computer Assistance in Lumbar Fusion Surgery: Analysis of 15 222 Patients in the ACS-NSQIP Database. AB - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: Several studies have shown that the accuracy of pedicle screw placement significantly improves with use of computer-assisted surgery (CAS). Yet few studies have compared the incidence of postoperative complications between CAS and conventional techniques. The objective of this study is to determine the difference in postoperative complication rates between CAS and conventional techniques in spine surgery. METHODS: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was used to identify patients who underwent posterior lumbar fusion from 2011 to 2013. Multivariate analysis was conducted to demonstrate the difference in postoperative complication rates between CAS and conventional techniques in spine surgery. RESULTS: Out of 15 222 patients, 14 382 (95.1%) were operated with conventional techniques and 740 (4.90%) were operated with CAS. Multivariate analysis showed that patients in the CAS group had fewer odds to experience adverse events postoperatively (odds ratio [OR] = 0.57, P < .001). Minor adverse events occurred in 2905 (20.2%) patients in the conventional group and in 98 (13.2%) patients in the CAS group (OR = 0.57, P < .001). Blood transfusion was present in 2488 (17.3%) of the patients in the conventional group compared to 81 (11.0%) of the patients in the CAS group (OR = 0.56, P < .001). The mean operative time in the conventional group was 205.2 +/- 106.1 minutes, and it was 227.0 +/- 111.9 minutes in the CAS group. This difference was statistically significant (r = 20.14, P < .001). CONCLUSION: This article examined the complications in lumbar spinal surgery with or without the use of CAS. These results suggest that CAS may provide a safer technique for implant placement in lumbar fusion surgeries. PMID- 28989840 TI - Trends Analysis of rhBMP Utilization in Single-Level Posterior Lumbar Interbody Fusion in the United States. AB - STUDY DESIGN: Retrospective study. OBJECTIVES: Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been widely used in spinal fusion surgery, but there is little information on rhBMP-2 utilization in single-level posterior lumbar interbody fusion (PLIF). The purpose of our study was to evaluate the trends and demographics of rhBMP-2 utilization in single-level PLIF. METHODS: Patients who underwent single-level PLIF from 2005 to 2011 were identified by searching ICD-9 diagnosis and procedure codes in the PearlDiver Patient Records Database, a national database of orthopedic insurance records. The year of procedure, age, gender, and region of the United States were recorded for each patient. Results were reported for each variable as the incidence of procedures identified per 100 000 patients searched in the database. RESULTS: A total of 2735 patients had single-level PLIF. The average rate of single-level PLIF with rhBMP-2 maintained at a relatively stable level (28% to 31%) from 2005 to 2009, but decreased in 2010 (9.9%) and 2011 (11.8%). The overall incidence of single level PLIF without rhBMP-2 (0.68 cases per 100 000 patients) was statistically higher (P < .01) compared to single-level PLIF with rhBMP-2 (0.21 cases per 100 000 patients). The average rate of single-level PLIF with rhBMP-2 utilization was the highest in West (30.1%), followed by Midwest (26.9%), South (20.5%), and Northeast (17.8%). The highest incidence of single-level PLIF with rhBMP-2 was observed in the age group <65 years (0.3 per 100 000 patients). CONCLUSIONS: To our knowledge, this is the first study to report on the demographics associated with rhBMP-2 use in single-level PLIF. There was a 3-fold increase in the rate of PLIF without rhBMP-2 compared to PLIF with rhBMP-2, with both procedures being mainly done in patients less than 65 years of age. PMID- 28989841 TI - Should We Label All Synovial Cysts as Unstable? AB - STUDY DESIGN: Retrospective study. OBJECTIVE: To analyze the various anatomical parameters that influence segmental stability in patients suffering from lumbar intra spinal cysts (LISCs) and to determine the outcome of microscopic unilateral laminotomy and cystectomy. METHODS: All patients that were surgically managed for a LISC between 2007 and 2013 with more than 3 years of follow-up were reviewed. Those without associated instability were evaluated for segmental mobility, segmental angulation, facet inclination, stage of disc degeneration, and level of involvement on MRI and dynamic radiographs. Outcomes of unilateral laminotomy and cystectomy were evaluated using VAS (Visual Analogue Score), ODI (Oswestry Disability Index), and Macnabs criteria. Dynamic radiographs were performed in all cases pre- and postoperatively and at the last follow-up. RESULTS: Thirty patients were operated for a LISC between 2007 and 2013. The levels involved were L4-5(23), L3-4(4) and L5-S1(3). The mean facet angle was 42.6 (+/- 6.1) degrees. The stage of disc degeneration was scattered haphazardly across all the cases (Gr 2[17]; Gr 3[1]; Gr 4[8]; Gr 5[4]). VAS and ODI scores improved significantly in all patients. Mean follow-up was 46.5 months (36-96 months). No patient developed postoperative instability at the last follow-up. CONCLUSIONS: The coronal inclination of the facet joints, absence of radiological instability, and poor co relation with stages of disc degeneration suggests the presence of adequate residual stability. In this study, stand-alone decompression for LISCs without instability had well sustained good/excellent outcomes. Fusion is recommended for LISCs with associated instability. PMID- 28989843 TI - A Novel Lumbar Motion Segment Classification to Predict Changes in Segmental Sagittal Alignment After Lateral Interbody Fixation. AB - STUDY DESIGN: Retrospective cohort study. OBJECTIVES: Lateral interbody fixation is being increasingly used for the correction of segmental sagittal parameters. One factor that affects postoperative correction is the resistance afforded by posterior hypertrophic facet joints in the degenerative lumbar spine. In this article, we describe a novel preoperative motion segment classification system to predict postoperative correction of segmental sagittal alignment after lateral lumbar interbody fusion. METHODS: Preoperative computed tomography scans were analyzed for segmental facet osseous anatomy for all patients undergoing lateral lumbar interbody fusion at 3 institutions. Each facet was assigned a facet grade (min = 0, max = 2), and the sum of the bilateral facet grades was the final motion segment grade (MSG; min = 0, max = 4). Preoperative and postoperative segmental lordosis was measured on standing lateral radiographs. Postoperative segmental lordosis was also conveyed as a percentage of the implanted graft lordosis (%GL). Simple linear regression was conducted to predict the postoperative segmental %GL according to MSG. RESULTS: A total of 36 patients with 59 operated levels were identified. There were 19 levels with MSG 0, 14 levels with MSG 1, 13 levels with MSG 2, 8 levels with MSG 3, and 5 levels with MSG 4. Mean %GL was 115%, 90%, 77%, 43%, and 5% for MSG 0 to 4, respectively. MSG significantly predicted postoperative %GL (P < .01). Each increase in MSG was associated with a 28% decrease in %GL. CONCLUSIONS: We propose a novel facet based motion segment classification system that significantly predicted postoperative segmental lordosis after lateral lumbar interbody fusion. PMID- 28989844 TI - Use of Intraoperative Ultrasound During Spinal Surgery. AB - STUDY DESIGN: Review and technical report. OBJECTIVE: Intraoperative ultrasound has been used by spine surgeons since the early 1980s. Since that time, more advanced modes of intraoperative imaging and navigation have become widely available. Although the use of ultrasound during spine surgery has fallen out of favor, it remains the only true real-time imaging modality that allows surgeons to visualize soft tissue anatomy instantly and continuously while operating. It is our objective to demonstrate that for this reason, ultrasound is a useful adjunctive technique for spine surgeons, especially when approaching intradural lesions or when addressing pathology in the ventral spinal canal via a posterior approach. METHODS: Using PubMed, the existing literature regarding the use of intraoperative ultrasound during spinal surgery was evaluated. Also, surgical case logs were reviewed to identify spinal operations during which intraoperative ultrasound was used. Illustrative cases were selected and reviewed in detail. RESULTS: This article provides a brief review of the history of intraoperative ultrasound in spine surgery and describes certain surgical scenarios during which this technique might be useful. Several illustrative cases are provided from our own experience. CONCLUSIONS: Surgeons should consider the use of intraoperative ultrasound when approaching intradural lesions or when addressing pathology ventral to the thecal sac via a posterior approach. PMID- 28989845 TI - Comparison Perioperative Factors During Minimally Invasive Pre-Psoas Lateral Interbody Fusion of the Lumbar Spine Using Either Navigation or Conventional Fluoroscopy. AB - STUDY DESIGN: Retrospective clinical study. OBJECTIVES: The aim of this study was to compare intraoperative conditions and clinical results of patients undergoing pre-psoas oblique lateral interbody fusion (OLIF) using navigation or conventional fluoroscopy (C-ARM) techniques. METHODS: Forty-two patients (22 patients by navigation and 20 by fluoroscopy) underwent the OLIF procedure at 2 medical centers, and records were reviewed. Clinical data was collected and compared between the 2 groups. Patients were followed-up with a range of 6 to 24 months. RESULTS: There were no significant differences on demographic data between groups. The navigation group had zero radiation exposure (RE) to the surgeon and radiation time compared to the C-ARM group, with total RE of 44.59 +/ 26.65 mGy and radiation time of 88.30 +/- 58.28 seconds (P < .05). The RE to the patient was significantly lower in the O-ARM group (9.38 mGy) compared to the C ARM group (44.59 +/- 26.65 mGy). Operating room time was slightly longer in the navigation group (2.49 +/- 1.35 hours) compared to the C-ARM group (2.30 +/- 1.17 hours; P > .05), although not statistically significant. No differences were found in estimated blood loss, length of hospitalization, surgery-related complications, and outcome scores with an average of 8-month follow-up. CONCLUSIONS: Compared with C-ARM techniques, using navigation can eliminate RE to surgeon and decrease RE to the patient, and it had no significant effect on operating time, estimated blood loss, length of hospitalization, or perioperative complications in the patients with OLIF procedure. This study shows that navigation is a safe alternative to fluoroscopy during the OLIF procedure in the treatment of degenerative lumbar conditions. PMID- 28989842 TI - Complications Associated With Spine Surgery in Patients Aged 80 Years or Older: Japan Association of Spine Surgeons with Ambition (JASA) Multicenter Study. AB - STUDY DESIGN: Retrospective study of registry data. OBJECTIVES: Aging of society and recent advances in surgical techniques and general anesthesia have increased the demand for spinal surgery in elderly patients. Many complications have been described in elderly patients, but a multicenter study of perioperative complications in spinal surgery in patients aged 80 years or older has not been reported. Therefore, the goal of the study was to analyze complications associated with spine surgery in patients aged 80 years or older with cervical, thoracic, or lumbar lesions. METHODS: A multicenter study was performed in patients aged 80 years or older who underwent 262 spinal surgeries at 35 facilities. The frequency and severity of complications were examined for perioperative complications, including intraoperative and postoperative complications, and for major postoperative complications that were potentially life threatening, required reoperation in the perioperative period, or left a permanent injury. RESULTS: Perioperative complications occurred in 75 of the 262 surgeries (29%) and 33 were major complications (13%). In multivariate logistic regression, age over 85 years (hazard ratio [HR] = 1.007, P = 0.025) and estimated blood loss >=500 g (HR = 3.076, P = .004) were significantly associated with perioperative complications, and an operative time >=180 min (HR = 2.78, P = .007) was significantly associated with major complications. CONCLUSIONS: Elderly patients aged 80 years or older with comorbidities are at higher risk for complications. Increased surgical invasion, and particularly a long operative time, can cause serious complications that may be life threatening. Therefore, careful decisions are required with regard to the surgical indication and procedure in elderly patients. PMID- 28989846 TI - Impact of Operation Time on 30-Day Complications After Adult Spinal Deformity Surgery. AB - STUDY DESIGN: Retrospective analysis of prospectively collected data. OBJECTIVE: There is a paucity of data on the effect of operative duration on postoperative complications during adult spinal deformity surgery (ASDS). The study attempts to explore and quantify the association between increased operation times and postoperative complications. METHODS: A retrospective cohort analysis was performed on the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database from 2010 to 2014. Patients (>=18 years of age) from the NSQIP database undergoing ASDS were separated into cohorts based on quartiles of operation duration. Chi-square and multivariate logistic regression models were used to identify risk factors. RESULTS: A total of 5338 patients met the inclusion criteria and were divided per quartiles based on operative duration in minutes (154, 235, 346, and 1156 minutes). Multivariate logistic regressions revealed that in comparison to the lowest quartile of operative duration, the highest quartile group was associated significantly with length of stay >=5 days (odds ratio [OR] = 5.85), any complication (OR = 9.88), wound complication (OR = 5.95), pulmonary complication (OR = 2.85, P = .001), venous thromboembolism (OR = 12.37), intra-/postoperative transfusion (OR = 12.77), sepsis (OR = 5.27), reoperations (OR = 1.48), and unplanned readmissions (OR = 1.29). The odds ratio was higher when comparing a higher quartile group with the reference group across all associations. P < .001 unless otherwise noted. CONCLUSION: ASDS operation time is associated with multiple postoperative complications, including, but not limited to, wound and pulmonary complications, venous thromboembolism, postoperative transfusion, length of stay >=5 days, sepsis, reoperation, and unplanned readmission. PMID- 28989847 TI - Comparison Between S2-Alar-Iliac Screw Fixation and Iliac Screw Fixation in Adult Deformity Surgery: Reoperation Rates and Spinopelvic Parameters. AB - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The S2-alar-iliac (S2AI) technique has been described as an alternative method for pelvic fixation in place of iliac screws (ISs) in spinal deformity surgery. The objective of this study was to analyze the impact of S2AI screws on radiographical outcomes, including spinopelvic parameters. METHODS: A retrospective review of 17 patients receiving ISs and 46 patients receiving S2AI screws for correction of adult spinal deformity between 2010 and 2015 with minimum 1-year follow-up was conducted. Patient data on postoperative complications, including reoperation rates and proximal junctional kyphosis (PJK), and radiographical parameters was collected and statistically analyzed. RESULTS: With mean follow-up of 21.1 months, the overall reoperation rate was significantly lower in the S2AI group than in the IS group (21.7% vs 58.8%, P = .01), but the incidence of PJK was similar (32.6% vs 35.3%, P > .99). Moreover, the time to reoperation in the IS group was significantly shorter than in the S2AI group (P = .001), and the S2AI group trended toward a longer time to reoperation due to PJK (P = .08). There was a significantly higher change in pelvic incidence (PI) in the S2AI group (-6.0 degrees ) compared with the IS group (P = .001). CONCLUSIONS: Compared with the IS technique, the S2AI technique demonstrated a lower rate of overall reoperation, a similar rate of PJK, longer time to reoperation, and possible reduction in PI. Future studies may be warranted to clarify the mechanism of these results and how they can be translated into improved patient care. PMID- 28989848 TI - Biomechanical Stability of a Stand-Alone Interbody Spacer in Two-Level and Hybrid Cervical Fusion Constructs. AB - STUDY DESIGN: In vitro human cadaveric biomechanical analysis. OBJECTIVE: To evaluate the segmental stability of a stand-alone spacer (SAS) device compared with the traditional anterior cervical plate (ACP) construct in the setting of a 2-level cervical fusion construct or as a hybrid construct adjacent to a previous 1-level ACP construct. METHODS: Twelve human cadaveric cervical spines (C2-T1) were nondestructively tested with a custom 6-degree-of-freedom spine simulator under axial rotation (AR), flexion-extension (FE), and lateral bending (LB) at 1.5 N m loads. After intact analysis, each specimen underwent instrumentation and testing in the following 3 configurations, with each specimen randomized to the order of construct: (A) C5-7 SAS; (B) C5-6 ACP, and C6-7 SAS (hybrid); (C) C5-7 ACP. Full range of motion (ROM) data at C5-C7 was obtained and analyzed by each loading modality utilizing mean comparisons with repeated measures analysis of variance with Sidak correction for multiple comparisons. RESULTS: Compared with the intact specimen, all tested constructs had significantly increased segmental stability at C5-C7 in AR and FE ROM, with no difference in LB ROM. At C5-C6, all test constructs again had increased segmental stability in FE ROM compared with intact (10.9 degrees +/- 4.4 degrees Intact vs SAS 6.6 degrees +/- 3.2 degrees , P < .001; vs.Hybrid 2.9 degrees +/- 2.0 degrees , P = .005; vs ACP 2.1 degrees +/- 1.4 degrees , P < .001), but had no difference in AR and LB ROM. Analysis of C6-C7 ROM demonstrated all test groups had significantly greater segmental stability in FE ROM compared with intact (9.6 degrees +/- 2.7 degrees Intact vs SAS 5.0 degrees +/- 3.0 degrees , P = .018; vs Hybrid 5.0 degrees +/- 2.7 degrees , P = .018; vs ACP 4.4 degrees +/- 5.2 degrees , P = .005). Only the hybrid and 2-level ACP constructs had increased stability at C6-C7 in AR ROM compared with intact, with no difference for all test groups in LB ROM. Comparison between test constructs demonstrated no difference in C5-C7 and C6-C7 segmental stability in all planes of motion. However, at C5-C6 comparison between test constructs found the 2-level SAS had significantly less segmental stability compared to the hybrid (6.6 degrees +/- 3.2 degrees vs 2.9 degrees +/- 2.0 degrees , P = .025) and ACP (6.6 degrees +/- 3.2 degrees vs 2.1 degrees +/- 1.4 degrees , P = .004). CONCLUSIONS: Our study found the currently tested SAS device may be a reasonable option as part of a 2-level hybrid construct, when used below an adjacent 1-level ACP, but should be used with careful consideration as a 2-level SAS construct. Consequences of decreased segmental stability in FE are unknown; however, optimal immediate fixation stability is an important surgical principle to avoid loss of fixation, segmental kyphosis, interbody graft subsidence, and pseudarthrosis. PMID- 28989849 TI - Can Posterior Lumbar Instrumentation and Fusion Be Overpowered by Anterior Lumbar Fusion With Hyperlordotic Cages? A Cadaveric Study. AB - STUDY DESIGN: Technical report on cadavers. OBJECTIVE: To evaluate preliminary feasibility and safety of lumbar sagittal alignment correction with anterior hyperlordotic cages used to overpower previous posterior spinal instrumentation. METHODS: Hyperlordotic 30 degrees anterior lumbar interbody fusion (ALIF) cages were inserted in collapsed L5-S1 disc space of 2 cadavers to overpower prior posterior L5-S1 pedicle screws and rod constructs. A distinct technique of opening up the disc space and creation of intersegmental lordosis was employed using a large endplate distractor and transforaminal lumbar interbody fusion (TLIF) paddle distractor. Assessment of increase in the intersegmental lordosis (ISL) was made using lateral fluoroscopic imaging. Postprocedural computed tomography (CT) scans were obtained to evaluate any failure of posterior instrumentation and to serve as a surrogate marker for bone quality. RESULTS: The 2 cadavers selected (from an available number of 10) were males: 82 and 84 years of age, respectively. Both had marked L5-S1 disc space collapse. The ISL achieved with hyperlordotic cages was 27.6 degrees for the first cadaver (up from 4.9 degrees ) and 23.1 degrees for the second one (up from 4.6 degrees ). No obvious screw-rod failure or cutout of instrumentation occurred. Postprocedure CT scans did not reveal any loosening of screws or cutout through endplates. Hounsfield unit values calculated on axial CT cuts were 73.50 (osteoporosis) and 80.70 (osteopenia) respectively for the 2 cadavers. CONCLUSION: Based on the results of the cadaveric experiment, overpowering of posterior instrumentation can be effectively achieved. Biomechanical and clinical studies are indicated to further evaluate the suitability and safety of this technique. PMID- 28989850 TI - Why Does C5 Palsy Occur After Prophylactic Bilateral C4-5 Foraminotomy in Open Door Cervical Laminoplasty? A Risk Factor Analysis. AB - STUDY DESIGN: Retrospective study. OBJECTIVES: To evaluate the efficacy of bilateral C4-5 foraminotomy in preventing occurrence of postoperative C5 palsy and to identify possible risk factors for its development. METHODS: A total of 70 consecutive patients who underwent open-door laminoplasty with bilateral C4-5 foraminotomy were included. Clinical, radiographic, and operative data was reviewed. Development of postoperative C5 palsy was analyzed. RESULTS: A total of 54 males and 16 females were reviewed. Mean age was 56 years (range, 30-86 years). The primary pathology was spondylosis in 76% of cases and ossified posterior longitudinal ligament in 21%. Radiographic evidence of C4-5 foraminal stenosis was seen in 81% of the patients. The mean duration of preoperative symptoms was 7 +/- 19 months. Four (5.7%) out of 70 patients developed C5 palsy after open-door laminoplasty with bilateral C4-5 foraminotomy. Multivariate analysis showed that a long duration of preoperative symptoms (>12 months) and the presence of preoperative C4-5 T2-MRI cord signal change were statistically significant risk factors for the development of C5 palsy even after bilateral C4 5 foraminotomy in open-door laminoplasty (P < .0001 and P = .036, respectively). CONCLUSIONS: Prophylactic bilateral C4-5 foraminotomies do not completely eliminate the occurrence of C5 palsy. Prolonged duration of symptoms and presence of preoperative T2-MRI cord signal change increase the risk for developing postoperative C5 palsy despite foraminotomy. PMID- 28989851 TI - Is There a Patient Profile That Characterizes a Patient With Adult Spinal Deformity as a Candidate for Minimally Invasive Surgery? AB - STUDY DESIGN: Retrospective review. OBJECTIVES: The goal of this study was to evaluate the baseline characteristics of patients chosen to undergo traditional open versus minimally invasive surgery (MIS) for adult spinal deformity (ASD). METHODS: A multicenter review of 2 databases including ASD patients treated with surgery. Inclusion criteria were age >45 years, Cobb angle minimum of 20 degrees , and minimum 2-year follow-up. Preoperative radiographic parameters and disability outcome measures were reviewed. RESULTS: A total of 350 patients were identified: 173 OPEN patients and 177 MIS. OPEN patients were significantly younger than MIS patients (61.5 years vs 63.74 years, P = .013). The OPEN group had significantly more females (87% vs 76%, P = .006), but both groups had similar body mass index. Preoperative lumbar Cobb was significantly higher for the OPEN group (34.2 degrees ) than for the MIS group (26.0 degrees , P < .001). The mean preoperative Oswestry Disability Index was significantly higher in the MIS group (44.8 in OPEN patients and 49.8 in MIS patients, P < .011). The preoperative Numerical Rating Scale value for back pain was 7.2 in the OPEN group and 6.8 in the MIS group preoperatively, P = .100. CONCLUSIONS: Patients chosen for MIS for ASD are slightly older and have smaller coronal deformities than those chosen for open techniques, but they did not have a substantially lesser degree of sagittal malalignment. MIS surgery was most frequently utilized for patients with an sagittal vertical axis under 6 cm and a baseline pelvic incidence and lumbar lordosis mismatch under 30 degrees . PMID- 28989852 TI - Editorial Perspective. PMID- 28989853 TI - Xenotransplantation: Where Are We with Potential Kidney Recipients? Recent Progress and Potential Future Clinical Trials. AB - PURPOSE: Inter-species transplantation, xenotransplantation, is becoming a realistic strategy to solve the organ shortage crisis. Here we focus on seminal publications that have driven research in xenotransplantation, as well as recently published literature and future endeavors. RECENT FINDINGS: Advances in gene editing technology have allowed for the efficient production of multi transgenic porcine donors leading improved xenograft survival in baboons, up to 2 years following heterotopic heart xenotransplantation and from weeks to several months following life-supporting kidney xenotransplanation. As technology evolves, additional challenges have arisen, including the development of proteinuria, early graft loss associated with porcine CMV, disparities in organ growth between donors and recipients as well as high-dose continuous immunosuppression requirements. To address these issues, our laboratory developed a tolerance-inducing protocol which has allowed for >6 months survival of a life supporting kidney with further approaches currently underway to address the challenges mentioned above. SUMMARY: Our recent findings, reviewed in this article, led us to develop methods to overcome obstacles, which, in conjunction with the work of others, are promising for future clinical applications of xenotransplantation. PMID- 28989854 TI - Identification and characterization of probiotic lactic acid bacteria isolated from traditional persian pickled vegetables. AB - Background: The pickle, a traditional fermented product, is popular among Iranians. Much research has been conducted worldwide on this food group. Due to a lack of related data in Iran, this study was conducted to isolate and identify dominant lactic acid bacteria (LAB) in pickles and salted pickles. Materials and methods: Seventy samples were collected from different regions of Iran. The isolated bacteria were identified as LAB by Gram staining and catalase by using MRS agar. Then, those strains were identified at the species level by physiological tests (e.g., gas production from glucose, arginine hydrolysis, CO2 production from glucose in MRS broth, carbohydrate fermentation) and growth at temperatures of 15 degrees C, 30 degrees C, and 45 degrees C in MRS broth for 3 days. The probiotic characteristics of these bacteria were studied using acid and bile tolerance. The corresponding results were verified using PCR analyses of the 16S rDNA region. Results: 114 presumptive lactic acid bacteria (LAB) with Gram positive and catalase-negative properties were obtained from the samples. The results revealed that all isolated bacteria were identfied as Lactobacillus (L.) plantarum, L. brevis, L. pentosus, L. casei, L. paracasei and Leuconostoc mesenteroides. The predominant LAB in these pickles was L. plantarum, which was isolated from most of the samples. Among the 114 LAB, 7 isolated species have probiotic potential. Six out of seven were recognized as L. plantarum and one remained unidentifiable by biochemical testing. PCR analysis and sequencing of the 16S rDNA region using 27f and 1522r primers showed that all of the probiotic strains were L. plantarum. Conclusion: The results of this study showed that the dominant LAB in traditional Persian pickled vegetables are L. plantarum, L. brevis, L. pentosus, L. casei, L. paracasei, and Leuconostoc mesenteroides. Moreover, L. plantarum was recognized as a probiotic species in pickled vegetables. The raw data obtained from this study can be used in the pickling industry to improve the nutritional value of products. PMID- 28989855 TI - Antimicrobial inhibitory activity of aqueous, hydroalcoholic and alcoholic extracts of leaves and stem of Daphne mucronata on growth of oral bacteria. AB - Background: Plants are a source of potential anti-infective agents. Daphne mucronata is a shrub in the family Thymelaeaceae, which has therapeutic effects. The aim of the present study was to evaluate the antimicrobial activity of aqueous, hydroalcoholic and alcoholic extracts of the leaves and stem of Daphne mucronata on the growth of oral bacteria. Materials and methods: Leaves and stem of Daphne mucronata were collected from the Zagros Mountains, Lorestan, Iran. They were air dried in the shade. Aqueous, hydroalcoholic and alcoholic extracts of Daphne mucronata were made by using classic techniques for solvent extraction of plant material. The antimicrobial effects of the Daphne mucronata extracts were evaluated using the agar disk diffusion method (ADDM) and the minimum inhibitory concentration (MIC). The data were analyzed using Duncan's test and ANOVA. Results: The results showed that the antimicrobial activity depended on the type of extract. The alcoholic extract of Daphne mucronata had the highest antibacterial activity and the highest effect on Streptococcus mutans. The aqueous extract of the plant had no effect on bacterial growth. Conclusion: On the basis of the current results, the alcoholic extract of Daphne mucronata might be promising as a natural antimicrobial agent and as a medicine for the prevention and control of the growth of Streptococcus mutans. PMID- 28989856 TI - Lead-free perovskite solar cells using Sb and Bi-based A3B2X9 and A3BX6 crystals with normal and inverse cell structures. AB - Research of CH3NH3PbI3 perovskite solar cells had significant attention as the candidate of new future energy. Due to the toxicity, however, lead (Pb) free photon harvesting layer should be discovered to replace the present CH3NH3PbI3 perovskite. In place of lead, we have tried antimony (Sb) and bismuth (Bi) with organic and metal monovalent cations (CH3NH3+, Ag+ and Cu+). Therefore, in this work, lead-free photo-absorber layers of (CH3NH3)3Bi2I9, (CH3NH3)3Sb2I9, (CH3NH3)3SbBiI9, Ag3BiI6, Ag3BiI3(SCN)3 and Cu3BiI6 were processed by solution deposition way to be solar cells. About the structure of solar cells, we have compared the normal (n-i-p: TiO2-perovskite-spiro OMeTAD) and inverted (p-i-n: NiO-perovskite-PCBM) structures. The normal (n-i-p)-structured solar cells performed better conversion efficiencies, basically. But, these environmental friendly photon absorber layers showed the uneven surface morphology with a particular grow pattern depend on the substrate (TiO2 or NiO). We have considered that the unevenness of surface morphology can deteriorate the photovoltaic performance and can hinder future prospect of these lead-free photon harvesting layers. However, we found new interesting finding about the progress of devices by the interface of NiO/Sb3+ and TiO2/Cu3BiI6, which should be addressed in the future study. PMID- 28989858 TI - Assessment of personal care and medical robots from older adults' perspective. AB - Demographic reports indicate that population of older adults is growing significantly over the world and in particular in developed nations. Consequently, there are a noticeable number of demands for certain services such as health-care systems and assistive medical robots and devices. In today's world, different types of robots play substantial roles specifically in medical sector to facilitate human life, especially older adults. Assistive medical robots and devices are created in various designs to fulfill specific needs of older adults. Though medical robots are utilized widely by senior citizens, it is dramatic to find out into what extent assistive robots satisfy their needs and expectations. This paper reviews various assessments of assistive medical robots from older adults' perspectives with the purpose of identifying senior citizen's needs, expectations, and preferences. On the other hand, these kinds of assessments inform robot designers, developers, and programmers to come up with robots fulfilling elderly's needs while improving their life quality. PMID- 28989857 TI - JC Polyomavirus Attachment and Entry: Potential Sites for PML Therapeutics. AB - PURPOSE OF REVIEW: JC polyomavirus (JCPyV) is a significant human pathogen that causes an asymptomatic infection in the kidney in the majority of the population. In immunosuppressed individuals, the virus can become reactivated and spread to the brain, causing the fatal, demyelinating disease progressive multifocal leukoencephalopathy (PML). There are currently limited treatment options for this fatal disease. Attachment to receptors and entry into host cells are the initiating events in JCPyV infection and therefore an attractive target for therapeutics to prevent or treat PML. This review provides the current understanding of JCPyV attachment and entry events and the potential therapeutics to target these areas. RECENT FINDINGS: JCPyV attachment and entry to host cells is mediated by alpha2,6-linked lactoseries tetrasaccharide c (LSTc) and 5 hydroxytryptamine receptors (5-HT2Rs), respectively, and subsequent trafficking to the endoplasmic reticulum is required for infection. Recently, vaccines, monoclonal antibodies, and small molecules have shown promise as anti-viral and PML therapies. SUMMARY: This review summarizes our current understanding of JCPyV attachment, entry, and trafficking and the development of potential PML therapeutics that inhibit these critical steps in JCPyV infection. PMID- 28989859 TI - Clarifying the Relationship between Trichotillomania and Anxiety. AB - Although research has consistently linked unidimensional anxiety with Trichotillomania (TTM) severity, the relationships between TTM severity and anxiety dimensions (i.e., cognitive and somatic anxiety) are unknown. This knowledge gap limits current TTM conceptualization and treatment. The current study examined these relationships with data collected from ninety-one adults who participated in a randomized clinical trial for TTM treatment. To examine whether the Beck Anxiety Inventory (BAI; Beck, Epstein, Brown, & Steer, 1988) could be used to measure multidimensional anxiety in TTM samples, we conducted a factor analysis. Results showed four emergent factors, including a cognitive factor and three somatic factors (neurophysiological, autonomic, and panic). Based on prior research, it was hypothesized that TTM severity would be related to the cognitive anxiety dimension and that psychological inflexibility would mediate the association. Hypotheses were not made regarding the relationship between TTM severity and somatic anxiety. Regression analyses indicated that only cognitive dimensions of anxiety predicted TTM severity and that psychological inflexibility mediated this relationship. Implications for the conceptualization and treatment of TTM are discussed. PMID- 28989860 TI - Model-based inference for small area estimation with sampling weights. AB - Obtaining reliable estimates about health outcomes for areas or domains where only few to no samples are available is the goal of small area estimation (SAE). Often, we rely on health surveys to obtain information about health outcomes. Such surveys are often characterised by a complex design, stratification, and unequal sampling weights as common features. Hierarchical Bayesian models are well recognised in SAE as a spatial smoothing method, but often ignore the sampling weights that reflect the complex sampling design. In this paper, we focus on data obtained from a health survey where the sampling weights of the sampled individuals are the only information available about the design. We develop a predictive model-based approach to estimate the prevalence of a binary outcome for both the sampled and non-sampled individuals, using hierarchical Bayesian models that take into account the sampling weights. A simulation study is carried out to compare the performance of our proposed method with other established methods. The results indicate that our proposed method achieves great reductions in mean squared error when compared with standard approaches. It performs equally well or better when compared with more elaborate methods when there is a relationship between the responses and the sampling weights. The proposed method is applied to estimate asthma prevalence across districts. PMID- 28989861 TI - Tackling vitamin A deficiency with biofortified sweetpotato in sub-Saharan Africa. AB - Orange-fleshed sweetpotato (OFSP) is a rich plant-based source of beta-carotene, which the body converts into vitamin A. In sub-Saharan Africa, sweetpotato is known as a food security crop but most varieties grown are high dry matter white fleshed types, lacking beta-carotene. In 1995, researchers recognized the potential of OFSP varieties to address widespread vitamin A deficiency in SSA using an integrated agriculture-nutrition approach. With their partners, they confronted conventional wisdom concerning food-based approaches and institutional barriers, to build the evidence base and breed 42 OFSP varieties adapted to farmer needs and consumer preferences. Subsequently, a multi-partner, multi-donor initiative, launched in 2009, has already reached 2.8 million households. This review summarizes that effort describing how the changing policy environment influenced the process. PMID- 28989862 TI - Bioprospecting North Atlantic microalgae with fast growth and high polyunsaturated fatty acid (PUFA) content for microalgae-based technologies. AB - Microalgae are considered to be an important and sustainable alternative to fish oil as a source for the polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Due to their health benefits, there is an increasing interest in the commercial application of these fatty acids (FA) to health and dietary products, and to aquaculture feeds. However, FA from microalgae are still expensive to produce compared to fish or plant oils. With only a few microalgal strains being cultivated on a large scale for commercial PUFA production, prospecting for new, robust and fast-growing strains with increased PUFA content is essential in order to reduce production costs. Microalgae from northern high latitudes, exposed to cold temperatures, may be especially promising candidates as previous studies have shown increasing unsaturation of FA in response to decreasing growth temperatures in different microalgae, most likely to maintain membrane fluidity and function. We have designed a screening pipeline, targeting a focused search and selection for marine microalgal strains from extreme North Atlantic locations with high robustness and biomass production, and increased levels of EPA and DHA. The pipeline includes a rational sampling plan, isolation and cultivation of clonal strains, followed by a batch growth experiment designed to obtain information on robustness, growth characteristics, and the FA content of selected isolates during both nutrient replete exponential cultivation and nutrient limited stationary cultivation. A number of clonal cultures (N = 149) have been established, and twenty of these strains have been screened for growth and FA content and composition. Among those strains, three showed growth rates >= 0.7 d- 1 at temperatures of 15 degrees C or below, and high amounts of EPA (> 3% DW), suggesting their potential as candidates for large scale production. PMID- 28989863 TI - Evaluation of a C57BL/6J * 129S1/SvImJ Hybrid Nestin-Thymidine Kinase Transgenic Mouse Model for Studying the Functional Significance of Exercise-Induced Adult Hippocampal Neurogenesis. AB - New neurons are continuously generated in the adult hippocampus but their function remains a mystery. The nestin thymidine kinase (nestin-TK) transgenic method has been used for selective and conditional reduction of neurogenesis for the purpose of testing the functional significance of new neurons in learning, memory and motor performance. Here we explored the nestin-TK model on a hybrid genetic background (to increase heterozygosity, and "hybrid vigor"). Transgenic C57BL/6J (B6) were crossed with 129S1/SvImJ (129) producing hybrid offspring (F1) with the B6 half of the genome carrying a herpes simplex virus thymidine kinase (TK) transgene regulated by a modified nestin promoter. In the presence of exogenously administered valganciclovir, new neurons expressing TK undergo apoptosis. Female B6 nestin-TK mice (n = 80) were evaluated for neurogenesis reduction as a positive control. Male and female F1 nestin-TK mice (n = 223) were used to determine the impact of neurogenesis reduction on the Morris water maze (MWM) and rotarod. All mice received BrdU injections to label dividing cells and either valganciclovir or control chow, with or without a running wheel for 30 days. Both the F1 and B6 background displayed approximately 50% reduction in neurogenesis, a difference that did not impair learning and memory on the MWM or rotarod performance. Running enhanced neurogenesis and performance on the rotarod but not MWM suggesting the F1 background may not be suitable for studying pro cognitive effects of exercise on MWM. Greater reduction of neurogenesis may be required to observe behavioral impacts. Alternatively, new neurons may not play a critical role in learning, or compensatory mechanisms in pre-existing neurons could have masked the deficits. Further work using these and other models for selectively reducing neurogenesis are needed to establish the functional significance of adult hippocampal neurogenesis in behavior. PMID- 28989864 TI - Flux Balance Analysis Indicates that Methane Is the Lowest Cost Feedstock for Microbial Cell Factories. AB - The low cost of natural gas has driven significant interest in using C1 carbon sources (e.g. methane, methanol, CO, syngas) as feedstocks for producing liquid transportation fuels and commodity chemicals. Given the large contribution of sugar and lignocellulosic feedstocks to biorefinery operating costs, natural gas and other C1 sources may provide an economic advantage. To assess the relative costs of these feedstocks, we performed flux balance analysis on genome-scale metabolic models to calculate the maximum theoretical yields of chemical products from methane, methanol, acetate, and glucose. Yield calculations were performed for every metabolite (as a proxy for desired products) in the genome-scale metabolic models of three organisms: Escherichia coli (bacterium), Saccharomyces cerevisiae (yeast), and Synechococcus sp. PCC 7002 (cyanobacterium). The calculated theoretical yields and current feedstock prices provided inputs to create comparative feedstock cost surfaces. Our analysis shows that, at current market prices, methane feedstock costs are consistently lower than glucose when used as a carbon and energy source for microbial chemical production. Conversely, methanol is costlier than glucose under almost all price scenarios. Acetate feedstock costs could be less than glucose given efficient acetate production from low-cost syngas using nascent biological gas to liquids (BIO-GTL) technologies. Our analysis suggests that research should focus on overcoming the technical challenges of methane assimilation and/or yield of acetate via BIO-GTL to take advantage of low-cost natural gas rather than using methanol as a feedstock. PMID- 28989866 TI - Choices and Challenges of Antibiotics Therapy in Diabetic Foot Infection. PMID- 28989867 TI - Medical Nutrition Therapy in Type 1 Diabetes Mellitus. PMID- 28989865 TI - Unveiling the role of tumor reactive stroma in cholangiocarcinoma: an opportunity for new therapeutic strategies. AB - Cholangiocarcinoma (CCA) is a very aggressive neoplasm, whose incidence has steadily increased in the last decade. Despite its growing epidemiological impact, therapeutic chances with a curative intent are still limited to surgical resection and, in highly selected cases, to liver transplantation. Unfortunately, in most cases at the time of diagnosis, CCA has already metastasized to regional lymph nodes, thereby reducing the opportunities for curative treatment. Mechanisms governing CCA invasiveness are unclear. A critical element of CCA is the abundant "tumor reactive stroma", which develops in close association with tumor growth. An abundant reactive stroma is present in a number of carcinomas characterized by strong invasiveness, namely gastric, colorectal and pancreatic cancers, as well as breast cancer. In tumor stroma, a variety of signals and mediators are reciprocally exchanged between stromal and cancer cells that, in turn acquire pro-invasive properties. These paracrine communications have started to be elucidated only recently, and may represent targets amenable of specific therapeutic intervention. In this review, we will highlight the cell types that compose the tumor reactive stroma in CCA and some of the molecular interactions possibly responsible for increased invasiveness of CCA. The possibility of dissecting, and likely exploiting, these interactions for potential new treatments will be also described. PMID- 28989868 TI - Glucocorticoid-induced Osteoporosis. PMID- 28989869 TI - "Riding High on Low Fuel" - Our Experience with Endogenous Hyperinsulinemic Hypoglycemia. AB - INTRODUCTION: Endogenous hyperinsulinemic hypoglycemia (EHH) is a condition in which the insulin levels are inappropriately high in the presence of low plasma glucose. MATERIALS AND METHODS: We did a retrospective analysis of case records of those patients admitted and evaluated for EHH from June 2004 to June 2016 in our center, excluding those that were diagnosed with reactive hypoglycemia. We collected data regarding demographics, clinical presentation, laboratory results, localization techniques, and treatment administered. RESULTS: Sixteen patients who were admitted for evaluation based on history suggestive of repeated hypoglycemic episodes were included in the study. All but one pregnant patient was subjected to a supervised fast in the hospital. All patients developed hypoglycemia (defined using Whipple's triad) within the first 24 h. Three patients had autoimmune hypoglycemia which differed significantly from insulinoma mediated hypoglycemia in certain clinical and laboratory parameters. They were older in age with marked fluctuations in the 24 h glucose profile ranging from frank hypoglycemia to frank hyperglycemia. The insulin levels were markedly elevated in this group of patients along with a significantly elevated insulin C peptide molar ratio (ICMR) when compared with patients with insulinoma-mediated hypoglycemia. CONCLUSIONS: Although insulinoma is the most common cause of EHH, autoimmune hypoglycemia should be considered as a differential diagnosis, particularly in older individuals with plasma glucose values increasing to the hyperglycemic range. Degree of elevation of insulin levels and ICMR may provide additional clues. Overall, the survival and prognosis of patients with EHH are excellent. PMID- 28989870 TI - Prepregnancy Hypothyroidism versus Gestational Hypothyroidism: A Comparative Study. AB - INTRODUCTION: Hypothyroidism managed inadequately in pregnancy may have grave outcomes for both mother and baby. Understanding pregnancy outcomes in our country with low awareness about thyroid diseases is important. OBJECTIVES: The objectives of the study were to evaluate demographic features and biochemical parameters in patients with prepregnancy hypothyroidism versus patients diagnosed to have primary hypothyroidism during pregnancy and to assess pregnancy outcomes. STUDY DESIGN: Prospective design. MATERIALS AND METHODS: The study was conducted in a tertiary care center in Bengaluru for 2 years. The patients were divided into two groups - Group I: Prepregnancy hypothyroidism and Group II: Hypothyroid during pregnancy. They were further staged according to ESI guidelines as subclinical or overt hypothyroidism. STATISTICAL ANALYSIS: Chi-square and Mann Whitney test. RESULTS: A total of 452 pregnant women with hypothyroidism were analyzed. The data of 371 delivered pregnancies were available. Group I and II had 196 (43.36%) and 256 (56.64%) patients, respectively. Age at presentation (years) was 27.09 +/- 4.19 in Group I versus 25.74 +/- 4.29 in Group II (P = 0.003); gestational age (weeks) was 9.04 +/- 5.41 in Group I versus 13.81 +/- 9.12 in Group II (P = 0.000). There was one case of congenital hypothyroidism in baby in each group. Mean birth weight was 2.90 +/- 0.39 kg in Group I versus 2.88 +/- 0.36 kg in Group II; P = 0.608. There were four abortions in Group I versus ten in Group II (P = 0.231), 104 cesarean sections in Group I compared to 133 in Group II; (P = 0.382). There was no difference in number of cesarean sections, abortions and low birth weight babies between overt and subclinical hypothyroidism subgroups. CONCLUSIONS: Group I patients presented earlier for testing suggesting awareness was good in this group. There was no difference in pregnancy outcome between the two groups. Overt versus subclinical status did not have any different effects on pregnancy outcomes in any group. PMID- 28989871 TI - Prevalence and Risk Factors for Peripheral Neuropathy among Type 2 Diabetes Mellitus Patients at a Tertiary Care Hospital in Coastal Karnataka. AB - CONTEXT AND OBJECTIVE: In view of the growing burden of type 2 diabetes mellitus (T2DM) globally and associated microvascular and macrovascular complications, the study was done to assess the prevalence and risk factors for diabetic neuropathy among T2DM patients attending a tertiary care hospital. SUBJECTS AND METHODS: T2DM patients' >=30 years of both gender, presenting to the Medicine Department at a tertiary care hospital were included in the study. Diabetic Neuropathy Symptom (DNS) questionnaire to assess symptoms and Diabetic Neuropathy Examination (DNE) scoring to assess clinical signs were used. RESULTS: A total of 273 patients were included. The mean age was 57.8 +/- 11.5 years. The male to female distribution was 75% (202) and 25% (71), respectively. According to DNS instrument, 41.4% patients scored positive for the presence of neuropathy while only 24.5% had neuropathy according to DNE score. The proportion of males affected by neuropathy was more than females. 43.1% males had a positive DNS score while only 27.2% of them had a positive DNE score. Duration of the disease was positively correlated with neuropathy. Neuropathy was more prevalent among people who had higher systolic and diastolic blood pressure as per DNS and DNE instruments. CONCLUSIONS: The present study identified a higher proportion of males to be affected by neuropathy. Hence, more detailed evaluation must be accorded to elderly male diabetic patients with longer duration of the disease. Lifestyle modifications and watchful screening need to be incorporated as part of routine patient health education during follow-up clinic visits. PMID- 28989872 TI - Current Indicators of Nutritional Care in Children with Type 1 Diabetes in India: Do we Need a National Nutritional Guideline? AB - BACKGROUND: Nutrition is an important pillar of management in children with type 1 diabetes. Indian food is heavily influenced by region, religion, traditions, seasons, and cultural choices. This survey was done to assess current practices and the need for India specific nutritional guidelines for children with type 1 diabetes. MATERIALS AND METHODS: Two 12-item questionnaires were administered to forty health-care professionals across India. The first questionnaire evaluated current clinical practice indicators for nutrition in these children and second assessed practices for counseling a child on dietary habits. RESULTS: There is great heterogeneity across the country with regard to dietary advice offered to children with type 1 diabetes. 97.5% of the respondents feel there is a need for an Indian dietary guideline for children with type 1 diabetes. CONCLUSION: There is need of India specific nutritional guidelines that should be made considering key variants such as age, region, cultural preference, economic burden and psychosocial beliefs, to offer guidance to diabetes care professionals. PMID- 28989873 TI - Effect of Metformin-sustained Release Therapy on Low-density Lipoprotein Size and Adiponectin in the South Indian Women with Polycystic Ovary Syndrome. AB - OBJECTIVES: The aim of the study is to compare surrogate markers of cardiovascular disease (CVD) risk, such as adiponectin (APN) levels and low density lipoprotein (LDL) size, before and after sustained release metformin (Met SR) therapy in women with polycystic ovarian syndrome (PCOS). METHODS: Sixty women with PCOS and sixty age-matched controls in the age group 18-45 years were recruited after obtaining informed consent. Women with PCOS were initiated on Met SR 1 g orally, which was increased to 1.5 g after 2 weeks and continued up to 24 weeks. Demographic data along with family history of type 2 diabetes mellitus, PCOS, and CVD were collected. Lipid profile plasma APN levels and LDL size were measured before and after therapy in the PCOS group. Data analysis was performed using the GraphPad Prism-5 software. RESULTS: Women with PCOS had greater dyslipidemia, lower APN level and LDL size, and increased lipid accumulating product index as compared to controls. After 6 months of Met-SR therapy, women with PCOS demonstrated significant increase in plasma APN levels and LDL size and significant decrease in weight, waist-hip ratio (WHR), waist circumference (WC), and blood pressure (BP). A significant decrease was observed in body mass index (BMI) in the overweight and obese PCOS subgroups. CONCLUSION: Met-SR increases LDL size, APN concentration and decreases weight, WC, WHR, and BP in patients with PCOS. Met-SR may have salutary effects on LDL particle size through effects on APN levels in women with PCOS. PMID- 28989874 TI - Metabolic Status and Hypogonadism in Human Immunodeficiency Virus-infected Males. AB - AIMS AND OBJECTIVES: The aim of this study is to determine the prevalence of hypogonadism in human immunodeficiency virus (HIV)-infected males and to study its relation to age, CD4 count, body mass index (BMI), duration of highly active antiretroviral therapy (HAART), and metabolic status. METHODOLOGY: Eighty-one HIV positive cases and 82 healthy controls were included in this case-control study. Each case underwent a complete physical examination and serum fasting plasma glucose, A1c, lipid profile, total testosterone (TT), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels were estimated. Serum TT level <300 ng/dl, or TT >300 ng/dl with high LH and FSH (compensatory hypogonadism) were taken as markers for hypogonadism, and it was correlated with age, CD4 count, duration of HAART, and metabolic status of the patient. RESULTS: Out of 81 cases, 21 (25.9%) were found to have hypogonadism as compared to 4 (4.9%) out of 82 controls. Of these 21, 14 cases had secondary hypogonadism, five had primary, and the remaining two had compensatory hypogonadism. The mean serum TT value among cases (371.7 +/- 102.9 ng/dl) was significantly lower than that among controls (419.7 +/- 71.5 ng/dl) (P = 0.007). Hypogonadism was found to be significantly associated with the age of the patient (P = 0.007), CD4 count (P = 0.002), and duration of HAART (P = 0.04) and was independent of the BMI (P = 0.9) and the waist circumference (P = 0.8). Dyslipidemia and dysglycemia were significantly more common among cases as compared to controls (P < 0.05) but were not associated with hypogonadism. CONCLUSION: The prevalence of hypogonadism is higher among HIV-infected males as compared to healthy individuals. Hypogonadism was significantly associated with age, CD4 count, and duration of HAART and was independent of BMI, glycemic status, and dyslipidemia. PMID- 28989875 TI - Bacteriological Profile of Diabetic Foot Ulcer with Special Reference to Drug resistant Strains in a Tertiary Care Center in North-East India. AB - AIM: This study was carried out to determine the bacteriological profile of infected diabetic foot ulcers (DFUs) and the antibiotic resistance pattern from the isolates. An attempt was made to suggest an empiric antibiotic regimen to treat such patients. MATERIALS AND METHODS: Tissue samples were collected from 150 patients between February 2015 and January 2016 with DFUs under aseptic precautions and they were processed as per the Clinical and Laboratory Standards Institute guidelines. RESULTS: A total of 185 bacterial isolates were obtained from 150 persons with diabetic and with foot ulcers. The age group of these persons ranged from 35 to 80 years and the maximum number of persons with DFUs was in the age group of 60-65 years. Among the isolates, Gram-negative bacilli were isolated in 112/185 (61%) and Gram-positive cocci in 73/185 (39%) cases. The most common isolate was Staphylococcus spp. 46 (25%), followed by Escherichia coli (20%) and Enterococcus spp. (15%). The antibiotic sensitivity profile of the bacteria was also studied. Among the isolates, 59/112 (53%) of the Gram-negative bacilli were extended spectrum beta-lactamase producers, 19/46 (41%) were methicillin-resistant Staphylococcus aureus, and 5/27 (19%) were vancomycin resistant Enterococcus. CONCLUSIONS: This study showed a preponderance of multidrug-resistant strains among the isolates from the DFUs. Knowledge on the antibiotic sensitivity pattern of the isolates will be helpful in determining the drugs for the empirical treatment of diabetic ulcers. Thus, indiscriminate use of antibiotics and chances of subsequent development of antibiotic resistance can also be reduced. PMID- 28989876 TI - Metabolic Derangement in Acute and Chronic Liver Disorders. AB - AIMS: This study aims to assess glycemic and lipid derangement in acute and chronic liver disorders. MATERIALS AND METHODS: A cross-sectional study was conducted on 104 patients diagnosed with acute or chronic liver disorder. Acute liver disease (ALD) patients were 40 and chronic liver disease (CLD) patients were 64. RESULTS: The mean value of fasting plasma glucose (FPG) in patients with ALD was 91.8 +/- 5.4 mg/dl and in CLD was 115.7 +/- 17.9 mg/dl, the difference was significant. The mean value of A1c was 4.3 +/- 0.6 in ALD and 6.1 +/- 0.8 in CLD, the difference was significant. In patients with CLD mean cholesterol was higher 177.4 +/- 28.8 mg/dl when compared to ALD 140 +/- 35.1 mg/dl, but the difference was not significant. ALD patients' high-density lipoprotein (HDL) was 50.4 +/- 5.1 mg/dl, and in CLD patients, HDL was 44.4 +/- 6.1 mg/dl. In CLD mean triglyceride (T) was 148.9 +/- 6.4 mg/dl while in ALD T was 134.8 +/- 14.2 mg/dl, the difference was significant. CONCLUSIONS: CLD is associated with glycemic derangement demonstrated by deranged FPG and A1c. In patients of ALD, no metabolic derangement was observed. PMID- 28989877 TI - Postpartum Follow-up in Women Diagnosed with Subclinical Hypothyroidism during Pregnancy. AB - BACKGROUND: Management guidelines about the thyroid disease in pregnancy are silent about the postpartum course of new onset subclinical hypothyroidism (SCH). Hence, we analyzed the 2 years outcome of SCH diagnosed during pregnancy. MATERIALS AND METHODS: We conducted this retrospective study using the medical records of patients with new onset SCH during pregnancy between 2010 and 2013 (n = 718). Patients who stopped their levothyroxine after delivery with a 2-year follow-up record were included. We excluded patients with known thyroid disorders and continuous use of drugs that affect the thyroid results. The patients were divided into two groups (Group 1 - euthyroid and Group 2 - hypothyroid) based on the final outcome after 2 years. The data were analyzed using appropriate statistical methods and a P < 0.05 was considered statically significant. RESULTS: A total of 559 (77.8%) women stopped levothyroxine after delivery, and the final follow-up data were available for 467 patients only. At the end of 2 years, 384 (82.2%) remained euthyroid, and the remaining 83 (17.8%) developed hypothyroidism. SCH and overt hypothyroidism were seen in 22 and 61 patients, respectively. Group 2 patients had higher mean age (25.5 vs. 23.6 years), goiter (51 vs. 2%), initial thyroid stimulating hormone (7.9 vs. 5.1 MUIU/mL), and thyroid antibody positivity (76 vs. 13%) (P < 0.001). CONCLUSION: The majority of patients with SCH during pregnancy remain euthyroid after delivery. Advanced age, goiter, positive family history, and thyroid autoimmunity increase the future risk of hypothyroidism in patients with SCH diagnosed during pregnancy. PMID- 28989878 TI - Prevalence of Metabolic Syndrome Markers among Women at 1-year Postpartum as per Prepregnancy Body Mass Index Status: A Longitudinal Study. AB - INTRODUCTION: Maternal body composition (BC) changes during lactation. Increased prepregnancy obesity is associated with poor obstetric outcomes. The aim was to study changes in maternal BC postpartum (PP) to 1-year PP with reference to their prepregnancy body mass index (BMI) status. METHODS: The study design was a 1-year follow-up study. Sixty-five apparently healthy primiparous women (28.6 +/- 3.4 years delivered full-term infants) were randomly selected from December 2010 to June 2013 and postclassified on the basis of their prepregnancy BMI status. Anthropometry, sociodemographic status, physical activity, diet, clinical examination, biochemical tests, and BC at total body (dual energy X-ray absorptiometry, GE, Lunar DPX) were collected using standardized protocols. RESULTS: Forty-one women were classified in Group A with normal prepregnancy BMI (20.4 +/- 2.0 kg/m2) and 24 women in Group B with overweight/obese (OW/OB) prepregnancy BMI (26.1 +/- 1.9 kg/m2). At 1 year, 75% of women returned to normal BMI in Group A, whereas all 100% of women from Group B remained in OW category at 1-year PP. Nearly 43% of Group B women showed the presence of at least two metabolic syndrome risk factors as compared to 36% in Group A at 1 year. CONCLUSION: Women with OW/OB prepregnancy BMI accumulated higher visceral fat with a higher prevalence of metabolic risk factors at 1-year PP. Our study underlines the importance of maintaining BMI status in reference range in reproductive years. PMID- 28989880 TI - Arrhythmias in Type 2 Diabetes Mellitus. AB - : Chronic hyperglycaemia of Type 2 diabetes mellitus causes long term damage to heart resulting in coronary artery disease (CAD), myocardial infarction (MI), congestive heart failure (CHF), and sudden death from arrhythmias. AIMS: To study the prevalence of different types of arrhythmias in T2DM, particularly in association with Cardiac Autonomic Neuropathy (CAN). METHODS: A cross-sectional study including 100 patients of Type 2 Diabetes Mellitus (T2DM) presenting with cardiac arrhythmias, was done at our hospital over 2 years. Detailed history along with physical examination and tests for CAN were done. Routine investigations along with echocardiography, stress test, Holter monitoring were done. RESULTS: Sinus Tachycardia (ST) was the commonest arrhythmia, found in 32% of patients. 20% had Complete Heart Block (CHB), 15% had Sinus Bradycardia (SB), and 15% had Atrial Fibrillation (AF). Ventricular Premature Complex (VPC) was found in 10% and 3% had Atrial Premature Complex (APC). 3% had first degree AV block, whereas 1% had Paroxysmal Supra Ventricular Tachycardia (PSVT), and another 1% had Ventricular Tachycardia (VT). Poorly controlled diabetes and co morbidities was associated with higher incidence of arrhythmias. 62% of patients had prolonged QTc, majority of which had CAN. Most of the patients responded to standard therapy. PMID- 28989879 TI - Root Cause Analysis of Diabetic Ketoacidosis Admissions at a Tertiary Referral Pediatric Emergency Department in North India. AB - OBJECTIVES: To identify system-based factors contributing to Emergency Department (ED) admissions of children with diabetic ketoacidosis (DKA) and related complications with emphasis on parental and physician awareness and prereferral management. MATERIALS AND METHODS: A prospective observational root cause analysis study of all consecutive admissions of children with DKA to pediatric ED of a tertiary care referral hospital in northern India over a period of 1 year (July 2010-June 2011). Prehospital, health-care system, referral, follow-up, and continuum of care related details were obtained through direct interview of parents and physicians and/or field observations for all enrolled children. RESULTS: Of the 30 children enrolled, 26 (86.6%) were referrals; 16 (61.5%) from first, 7 (26.9%) from second, and 3 (11.5%) from third health-care facility. More than half (n [%], 18 [60%]) had new onset diabetes and belonged to lower socioeconomic strata. Twenty-two (73.3%) were complicated DKA; shock (n [%], 19 [63%]), hypokalemia (n [%], 11 [36%]), and CE (n [%], 3 [10%]) were the most common complications. Most parents were ignorant of diabetes, its symptoms or complicating DKA. Nearly, half of the cases remained undiagnosed (n = 11) at first contact health-care facility; more so for new onset as compared to known diabetes (9/18 vs. 2/8; P = 0.022). The referring hospitals had limited facilities for rapid blood glucose estimation (n [%], 12 [40%]), blood gas analysis (n [%], 6 [20%]) and insulin infusion. On univariate analysis, patients with missed/delayed diagnosis more often had severe and complicated DKA. CONCLUSION: Parental ignorance, lower socioeconomic status, lack of clinical experience, and limited primary health-care facilities were root causes for severe and complicated DKA. PMID- 28989881 TI - Iodine Status among Subclinical and Overt Hypothyroid Patients by Urinary Iodine Assay: A Case-Control Study. AB - OBJECTIVES: The objective of the study was to assess the differences of iodine status as measured by urinary iodine excretion (UIE) between cases of hypothyroidism and healthy controls. MATERIALS AND METHODS: The study was conducted in cases with subclinical hypothyroidism (n = 58) and overt hypothyroidism (n = 41) and compared with age- and sex-matched healthy euthyroid controls (n = 52) attending Universal College of Medical Sciences Teaching Hospital, Bhairahawa, Nepal. Serum free triiodothyronine (fT3), free thyroxine (fT4), and thyroid-stimulating hormone (TSH) were estimated by competitive ELISA and sandwich ELISA, respectively (Diametra, Italy). The urinary iodine concentration (UIC) in urine samples was estimated by ammonium persulfate digestion method recommended by the WHO. RESULTS: A significantly higher median UIC was observed among cases of subclinical hypothyroidism (224.90 MUg/l) and overt hypothyroidism (281.0 MUg/l) as compared to the controls (189.90 MUg/l) (P = 0.0001, P = 0.001). Serum TSH in the cases of subclinical hypothyroid was higher, whereas fT3 was lower as compared to controls (P = 0.028, P = 0.0001), respectively. Similarly, serum TSH in the cases of overt hypothyroid was higher and fT3 and fT4 were lower as compared to controls (P = 0.0001, P = 0.0001, P = 0.015), respectively. There was positive correlation of UIC with TSH (r = 0.269, P = 0.0001), whereas negative correlation was seen with fT3 (r = -0.328, P = 0.0001) and fT4 (r = -0.145, P = 0.076). The test of multiple regression has shown that fT3 (beta = -0.262, P = 0.012) as an independent predictor in association with UIE in cases. CONCLUSION: Excessive iodine intake was found in hypothyroid patients as assessed by UIE concluding that it may trigger the thyroid hypofunction. Cohort studies to generate further evidence should be done to explore potential mechanism of hypothyroidism in excess iodine intake. PMID- 28989882 TI - Effect of Short-term Erythropoietin Therapy on Insulin Resistance and Serum Levels of Leptin and Neuropeptide Y in Hemodialysis Patients. AB - INTRODUCTION: Insulin resistance (IR) is a known complication of end-stage kidney disease (ESKD). It may be an important therapeutic target in stages of chronic kidney disease. AIM: The study was conducted to evaluate the effect of short-term treatment with recombinant human erythropoietin (rHuEpo) therapy on IR, serum leptin, and neuropeptide Y in ESKD patients on hemodialysis. MATERIALS AND METHODS: Thirty ESKD patients were enrolled in the study and were randomly assigned into two groups. Erythropoietin (rHuEpo) group consisted of 15 patients (7 females, 8 males, mean age 47.8 +/- 9.3 years) treated with rHuEpo therapy after each session of dialysis. No-rHuEpo group consisted of 15 patients (7 females, 8 males, mean age 45.5 +/- 8.6 years) not treated with rHuEpo. In addition to, control group consisted of 15 healthy controls (6 females, 9 males, mean age 48.8 +/- 11 years). RESULTS: The mean fasting insulin (11 +/- 4.2 mU/L) and homeostatic model assessment of IR (HOMA-IR) test (2.6 +/- 1.1) were significantly higher in ESKD patients than control group (6.6 +/- 1.4 mU/L and 1.5 +/- 0.3, respectively). There were significant decreases in glycated hemoglobin (HbA1c) (5.6 +/- 1%), fasting insulin level (9.3 +/- 3.1 MUU/mL), HOMA IR (2.2 +/- 0.7), and serum leptin levels (17.4 +/- 8.7 ng/mL) also significant increase in neuropeptide Y levels (113 +/- 9.9 pg/mL) after 3 months of rHuEpo therapy, in addition to further significantly decrease fasting insulin levels (7.1 +/- 2.1 MUU/mL) and HOMA-IR (1.7 +/- 6) after 6 months in rHuEpo group. In contrast, there were significantly increases in HbA1c% (5.9 +/- 0.5%) and leptin levels (42.3 +/- 25.3 ng/mL) in No-rHuEpo group throughout the study. CONCLUSION: IR and hyperleptinemia are improved by recombinant human erythropoietin therapy. PMID- 28989883 TI - Status of Serum Vitamin D and Calcium Levels in Women of Reproductive Age in National Capital Territory of India. AB - CONTEXT: In India, Vitamin D deficiency is a major public health problem, associated with lack of sunlight exposure in spite of abundant sunshine usually accompanied by reduced dietary intake. In women of reproductive age, Vitamin D deficiency in pregnancy has been associated with an increased risk of gestational diabetes mellitus, preeclampsia, maternal and perinatal morbidity and mortality. AIMS: The aim of the present cross-sectional study was to evaluate the levels of serum Vitamin D 25(OH) D and calcium in women of reproductive age from India. SETTINGS AND DESIGN: A cross-sectional study was carried on a total of 224 healthy nonpregnant and nonlactating women in the reproductive age group of 20-49 years. MATERIALS AND METHODS: Demographic, socioeconomic class, and biochemical parameters for the estimation of serum 25(OH)D and calcium levels in women of reproductive age were studied. STATISTICAL ANALYSIS: Statistical Package for Social Sciences version 20.0 was utilized for conducting the statistical analysis of the data. RESULTS: Vitamin D deficiency (<20 ng/ml) was present in 88% of women. Women from middle socioeconomic class had the lowest mean serum 25(OH) D levels (9.6 +/- 6 ng/ml) as compared to women from upper middle (11.4 +/- 8 ng/ml), lower (11.2 +/- 8 ng/ml), and upper (10 +/- 8.6 ng/ml) socioeconomic class. Serum calcium levels were found in the normal range of 8.5-10.5 mg/dl for all the study subjects. CONCLUSIONS: There is a high prevalence of hypovitaminosis D among women of reproductive age. These women may possibly have a higher risk of development of osteoporosis and pregnancy-related complications in future life. PMID- 28989884 TI - Diagnosis of Adrenocortical Tumors by Reticulin Algorithm. AB - AIMS: To apply reticulin algorithm (RA) to the diagnosis of adrenocortical tumors on adrenalectomy specimens and compare its efficacy to the modified Weiss criteria or Lin-Weiss-Bisceglia (LWB) criteria for oncocytic variant. MATERIALS AND METHODS: Adrenocortical tumors (ACTs) diagnosed on resected specimens including the variants during January 2010-June 2016 were retrieved from the pathology records. The demographic and clinical data were obtained from medical records. The functional status of the tumor was noted based on clinical and biochemical evaluation. The location, size, and gross appearance of the tumor were noted. The corresponding hematoxylin and eosin-stained slides were independently assessed by two pathologists applying modified Weiss criteria and LWB criteria for the oncocytic variant as applicable. Reticulin stain was performed on representative sections in all cases. All the tumors were classified according to RA, and the diagnoses made by each system were correlated. RESULTS: There were 15 ACTs in the study period. There were two adenomas including one oncocytoma which showed Weiss score (WS) of 2 and intact reticulin framework. There were 13 adrenal cortical carcinomas including two oncocytic variants with WS ranging from 4 to 7. There was disruption of reticulin and thick, irregular reticulin fibers in all tumors, irrespective of the histology. It correlated with modified Weiss and LWB criteria. CONCLUSIONS: The RA was simple, easy to apply, and correlated well with modified Weiss criteria in the diagnosis of ACTs including the oncocytic variant. PMID- 28989885 TI - Impact of Severity of Illness on the Function of the Hypothalamo-pituitary gonadal Axis in Postmenopausal Women with Acute Severe Illness: Implications for Predicting Disease Outcome. AB - BACKGROUND: While elevated levels of estradiol were predictive of mortality in critically ill surgical and trauma patients, their ability to predict outcome in nonsurgical patients has not been studied. We aimed to study the determinants of gonadotropin levels in acutely ill postmenopausal women with nonsurgical disease and the impact of changes in the gonadal axis on the outcome of these patients. METHODS: Thirty-five postmenopausal women admitted to medical intensive care with acute severe illness and having a Simplified Acute Physiology Score (SAPS II score) >=30 (in-hospital mortality rate >= 10%) were recruited. On the 5th day of hospitalization, fasting samples were collected at 8.00 am and tested for luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, free triiodothyronine, free thyroxine, thyrotropin, cortisol, prolactin, dehydroepiandrosterone, androstenedione, and sex hormone-binding globulin. Multiple linear regression analysis was performed to identify independent determinants if any of LH and FSH. Receiver operating characteristic (ROC) curves were drawn for different cutoffs of LH, FSH, and estradiol to diagnose mortality and prolonged hospitalization. RESULTS: There was an independent negative association between the FSH and the SAPS II score (beta = -0.435; P = 0.014), but not with any of the other tested parameters (estradiol, prolactin, or cortisol). Among components of the SAPS II score, the total leukocyte count (TLC) was negatively associated with serum FSH (beta coefficient = -0.635, P = 0.013). None of these parameters were determinants of LH. On ROC analysis, neither estradiol nor gonadotropins were diagnostic for in-hospital mortality. However, among survivors, low estradiol was diagnostic for prolonged hospital stay (area under the curve = 0.785; P = 0.015). CONCLUSION: FSH, but not LH, is negatively associated with the severity of illness, particularly to its inflammatory component (TLC). Low estradiol in survivors was a predictor of prolonged hospital stay. PMID- 28989886 TI - Comparative Evaluation of Safety and Efficacy of Glimepiride and Sitagliptin in Combination with Metformin in Patients with Type 2 Diabetes Mellitus: Indian Multicentric Randomized Trial - START Study. AB - BACKGROUND AND OBJECTIVE: Modern sulfonylureas like glimepiride offer effective glycemic control with extrapancreatic benefits and good tolerability. The objective of the present study was to evaluate and compare safety and efficacy of glimepiride and sitagliptin in combination with metformin in patients with type 2 diabetes mellitus (T2DM). METHODS: In this open-label, randomized, comparative, multicenter study, a total of 305 T2DM patients who were either drug naive or uncontrolled on metformin were randomized to glimepiride 1 or 2 mg/sustained release metformin 1000 mg once daily (glimepiride group, n = 202) or sitagliptin 50 mg/metformin 500 mg twice daily (sitagliptin group, n = 103) for 12 weeks. Primary endpoint was change in glycosylated hemoglobin (HbA1c). Secondary endpoints were change in fasting plasma glucose (FPG), postprandial plasma glucose (PPG), body mass index (BMI) and to assess overall safety profile. RESULTS: At 12 weeks, there was a statistically significant difference in the mean HbA1c reduction in glimepiride group (0.42%) as compared to sitagliptin group (0.30%) (P = 0.001). Mean reduction in FPG and PPG was also statistically significant in the glimepiride group as compared to the sitagliptin group (P = 0.008). There was no significant difference in terms of change in BMI (0.07 +/- 0.39 kg/m2 vs. 0.08 +/- 0.31 kg/m2) in glimepiride and sitagliptin groups, respectively, (P = 0.644) between both the groups. The incidences of hypoglycemic events were also comparable among both the groups. CONCLUSION: In T2DM patients, glimepiride/metformin combination exhibited significant reduction in glycemic parameters as compared to sitagliptin/metformin combination. Moreover, there was no significant difference between both the groups in terms of change in BMI and incidence of hypoglycemia. PMID- 28989887 TI - A Pragmatic Approach to the Indeterminate Thyroid Nodule. AB - Thyroid nodules are prevalent in upto 68% of randomly selected individuals in whom high resolution ultrasound is performed. The majority of nodules are benign. The use of ultrasound coupled with FNAC has dramatically reduced the number of patients who undergo surgery for nodules. The six tier Bethesda scoring system has reduced variability and increased the ability to clinicians to guide patients with thyroid nodules. There is good correlation between cytology and histopathologic outcomes. A significant proportion of patients will however fall into an indeterminate category. The availability of molecular markers enhanced with next generation sequencing technology and the expression classifier are added diagnostic aids that can help in management. However these are not available in many countries and in resource limited settings. A pragmatic approach to the diagnosis of indeterminate nodules includes utilising pre and post test probability, clinical acumen, correlation of ultrasound findings and expert opinion in some settings. Using this approach high risk patients can be appropriately chosen for surgery while relegating patients with lower risk to watchful followup. PMID- 28989888 TI - Sleep Disorders in Type 2 Diabetes. AB - Type 2 diabetes mellitus (T2DM) has shown to be associated with higher incidence of sleep disorders, which may be due to disease itself or because of secondary complications or associated comorbidities associated with diabetes. On the other hand, shorter sleep duration and erratic sleep behavior itself have been linked with higher incidence of obesity, metabolic syndrome, and T2DM. Assessment of sleep quality and sleep disorders as a part of the comprehensive medical evaluation is recommended based on emerging evidence suggesting a relationship between sleep quality and glycemic control in persons with T2DM. In this review, we attempt to summarize common sleep disorders associated with T2DM, their impacts on glycemic and other metabolic control, and various preventive and therapeutic strategies to tackle these problems. PMID- 28989889 TI - Sodium-glucose Cotransporter 2 Inhibitor Use: A Pharmaco-ergonomic Qualification Tool. AB - Pharmaco-ergonomics implies tailoring the drug therapy to an individual patient's requirement(s). The development of sodium-glucose cotransporter 2 inhibitor (SGLT2-i) agents has impelled multiple clinical considerations, in the management of type-2 diabetes. This paper attempts to summarize the pharmaco-ergonomic considerations for these agents, in the form of an SGLT2-i qualification tool, based on a clinical score. This tool may serve as a simple and inexpensive practical guide, to optimize the risk-benefit considerations for SGLT2-i agents. PMID- 28989892 TI - Management of Primary Adrenal Insufficiency: Review of Current Clinical Practice in a Developed and a Developing Country. AB - Treatment of primary adrenal insufficiency (PAI) requires lifelong hormone replacement with glucocorticoids (GCs) and mineralocorticoids. Impaired quality of life and increased standardized mortality ratio in these patients emphasize the importance of tailoring therapy to individual needs. Role of education is paramount in improving patient compliance and in anticipating and preventing adrenal crises. Although discovery of synthetic GCs was a major breakthrough in treatment of patients with this life-threatening condition, management of PAI continues to be challenging. The obstacles for clinicians appear to vary widely across the globe. While optimization and individualization of therapy after diagnosis of PAI remain the main challenges for clinicians in the developed world, doctors in a developing country face problems at almost every stage from the diagnosis to the treatment and follow-up of these patients; cost of therapy, lack of resources, and funding are the main hindrances. Adherence to therapy and patient education are found to be common issues in most parts of the world. This commentary highlights the challenges from both developed and developing country's perspective in treating PAI; it also provides an update on current management scenario and future treatment options. PMID- 28989891 TI - Effect of a Low-Calorie Diet on Restoration of Normoglycemia in Obese subjects with Type 2 Diabetes. AB - INTRODUCTION: Type 2 diabetes mellitus (T2DM) is considered to be an inevitably progressive disease. Complex therapies add to the financial and psychological burden. Very low-calorie diets (LCDs) are emerging as an option in the management of type 2 diabetes. METHODS: We performed a clinical audit of patients with T2DM who received 12 weeks of LCD. RESULTS: This case series documents that 6 out of 12 participants (median baseline HbA1c 9%) achieved HbA1c level in nondiabetes range with LCD despite stopping all antidiabetes medications. There was an improvement in serum triglycerides, HDL cholesterol, total cholesterol, C Reactive protein, urine microalbumin, liver transaminases, liver fat and the indices of insulin resistance, beta cell secretory capacity, and insulin sensitivity. CONCLUSION: If long-term follow-up proves sustained benefits, such dietary restriction may be an alternative to more drastic options for reversal of type 2 diabetes. This may also help in changing the treatment perspective of a newly detected T2DM from an incurable and inevitably progressive disease to a potentially reversible disease. PMID- 28989890 TI - Systematic Review on Vitamin D Level in Apparently Healthy Indian Population and Analysis of Its Associated Factors. AB - BACKGROUND: Vitamin D which is involved in the maintenance of bone mineral homeostasis has been found to portray various pleiotropic effects. Although it has been widely accepted that serum 25-hydroxy Vitamin D level above 30 ng/ml is considered optimal for the biological actions of Vitamin D, there is a need to explore the levels of Vitamin D reported among Indians from various regions of the country. Hence, this systematic review aims to appraise the status of Vitamin D levels reported from apparently healthy Indians across various parts of India. METHODOLOGY: A comprehensive literature search was carried out to identify the range of Vitamin D levels among apparently healthy individuals from various parts of India, with the search term "Vitamin D and India" in the search portals of PubMed, Google Scholar, Indmed, and ScienceDirect. A total of 2998 articles were retrieved by the above search strategy, of which only forty studies fulfilled the criteria to be included in the systematic review. Studies done in various states were compiled under the respective zones based on the classification of Indian zones as specified in Zonal maps of India. RESULTS: The level of Vitamin D from all the forty included studies ranged from 3.15 +/- 1.4 to 52.9 +/- 33.7 ng/ml. The effect size of Vitamin D level was higher in the South Zone compared to other zones. CONCLUSION: The present study shows that Vitamin D deficiency is prevalent among apparently healthy Indians living in different regions of India, irrespective of their exposure to sunlight. PMID- 28989893 TI - An Intriguing Family with Type 2 Diabetes Mellitus and Complete Heart Block. AB - Chronic hyperglycaemia of Type 2 Diabetes Mellitus (T2DM) causes long term damage to heart resulting in coronary artery disease (CAD), myocardial infarction (MI), congestive heart failure (CHF), and sudden death from arrhythmias. A 62 year old male presented to our emergency with complaint of sudden onset giddiness from last 2 hours. This was followed by loss of consciousness. Patient was a known case of T2DM since last 1 year. Family history- patient has two brothers who also have T2DM and both of them also developed Complete Heart Block (CHB) spontaneously. The patient's mother also had T2DM and she also developed CHB. On examination of the cardiovascular system, pulse rate was 36 per minute and a variable intensity of first heart sound was present. Rest of the cardiovascular examination and other system examination was within normal limits. Routine investigations were within normal limits and ECG showed CHB. Echocardiography revealed normal ventricular function with no evidence of ischemic heart disease. This was a case of Type 2 DM and spontaneous onset CHB with a strong family history. This case underscores the fact that CHB can occur spontaneously in Type 2 diabetics without ischemic heart disease. The cause of CHB was most likely Cardiac Autonomic Neuropathy (CAN), which is determined not only by poor glycaemic control, metabolic derangements and duration of diabetes but also by genetic factors (likely maternal). PMID- 28989894 TI - Endocrine Covfefe. PMID- 28989895 TI - Verapamil in Diabetes. PMID- 28989896 TI - Diagnostic efficacy of a modified low-dose acquisition protocol for the preoperative evaluation of mini-implant sites. AB - PURPOSE: The objective of this study was to compare the outcomes of surgical mini implant placement when potential mini-implant sites were scanned using a lower dose 180 degrees acquisition protocol versus a conventional 360 degrees acquisition protocol. MATERIALS AND METHODS: Ten dentate human skulls were used to provide sites for potential mini-implant placement. The sites were randomly divided into 2 groups: 360 degrees and 180 degrees cone-beam computed tomography (CBCT) acquisition protocols. A small-volume 180 degrees CBCT scan and a 360 degrees CBCT scan of each site were acquired using a Morita Accuitomo 170 CBCT machine and then a mini-implant was placed. A follow-up 360 degrees CBCT scan was done as a gold standard to evaluate the location of the mini implant and root perforation. Two raters evaluated the scans. RESULTS: Ninety eight percent of the mini-implants placed did not perforate any root structure. Two percent of the sites had an appearance suggestive of perforation. On a Likert scale, both raters agreed that their subjective evaluation of the diagnostic quality of the protocols, ability to make and read measurements of the sites, and preferences for the specified diagnostic task were comparable. The Cohen kappa showed high inter-rater and intra-rater agreement. CONCLUSION: In this ex vivo study, we found that the 180 degrees rotational acquisition was as effective as the conventional 360 degrees rotational acquisition for the preoperative evaluation of potential mini-implant sites. PMID- 28989897 TI - Three-dimensional analysis of impacted maxillary third molars: A cone-beam computed tomographic study of the position and depth of impaction. AB - PURPOSE: The classification of impacted maxillary third molars (IMTMs) facilitates interdisciplinary communication and helps estimate the degree of surgical difficulty. Thus, this study aimed to develop a 3-dimensional classification of the position and depth of impaction of IMTMs and to estimate their prevalence with respect to gender and age. MATERIALS AND METHODS: This cross-sectional retrospective study analyzed images in sagittal and coronal cone beam computed tomography (CBCT) sections of 300 maxillary third molars. The proposed classification was based on 3 criteria: buccolingual position (buccal, lingual, or central), mesial-distal position (mesioangular, vertical, or distoangular), and depth of impaction (low, medium, or high). CBCT images of IMTMs were classified, and the associations of the classifications with gender and age were examined using analysis of variance with the Scheffe post-hoc test. To determine the associations among the 3 classifications, the chi-square test was used (P<.05). RESULTS: No significant association of the classifications with gender was observed. Age showed a significant relationship with depth of impaction (P=.0001) and mesial-distal position (P=.005). The most common positions were buccal (n=222), vertical (n=184), and low (n=124). Significant associations among the 3 tested classifications were observed. CONCLUSION: CBCT enabled the evaluation of IMTMs in a 3-dimensional format, and we developed a proposal for a new classification of the position and depth of impaction of IMTMs. PMID- 28989898 TI - Distances from the root apices of posterior teeth to the maxillary sinus and mandibular canal in patients with skeletal open bite: A cone-beam computed tomography study. AB - PURPOSE: This study determined and compared the distances from the maxillary root apices of posterior teeth to the floor of the maxillary sinus, or maxillary sinus distances (MSDs), and the distances from the mandibular root apices of the posterior teeth to the mandibular canal, or mandibular canal distances (MCDs), in Thai subjects with skeletal open bite and skeletal normal bite. MATERIALS AND METHODS: Pretreatment cone-beam computed tomography (CBCT) images were obtained from 30 Thai orthodontic patients (15 patients with skeletal normal bite and 15 with skeletal open bite) whose ages ranged from 14 to 28 years. The CBCT images of the patients were processed and measured using the Romexis Viewer program. The MSDs and MCDs from the root apices of the maxillary and mandibular second premolar, first molar, and second molar to the maxillary sinus floor or the mandibular canal were measured perpendicularly to the occlusal plane. The Student t test was used for comparisons between the 2 groups. RESULTS: The greatest mean MSDs were from the root apex of the second premolars in both groups, whereas the least mean MSDs were from the mesiobuccal root apex of the second molars. The greatest mean MCDs were from the mesial root apex of the first molars, whereas the least mean MCDs were from the distal root apex of the second molars. CONCLUSION: There were no differences in the mean MSDs or the mean MCDs between the skeletal normal bite group and the skeletal open bite group. PMID- 28989899 TI - Volumetric accuracy of cone-beam computed tomography. AB - PURPOSE: This study was performed to investigate the influence of object shape and distance from the center of the image on the volumetric accuracy of cone-beam computed tomography (CBCT) scans, according to different parameters of tube voltage and current. MATERIALS AND METHODS: Four geometric objects (cylinder, cube, pyramid, and hexagon) with predefined dimensions were fabricated. The objects consisted of Teflon-perfluoroalkoxy embedded in a hydrocolloid matrix (Dupli-Coe-Loid TM; GC America Inc., Alsip, IL, USA), encased in an acrylic resin cylinder assembly. An Alphard Vega Dental CT system (Asahi Roentgen Ind. Co., Ltd, Kyoto, Japan) was used to acquire CBCT images. OnDemand 3D (CyberMed Inc., Seoul, Korea) software was used for object segmentation and image analysis. The accuracy was expressed by the volume error (VE). The VE was calculated under 3 different exposure settings. The measured volumes of the objects were compared to the true volumes for statistical analysis. RESULTS: The mean VE ranged from 4.47% to 2.35%. There was no significant relationship between an object's shape and the VE. A significant correlation was found between the distance of the object to the center of the image and the VE. Tube voltage affected the volume measurements and the VE, but tube current did not. CONCLUSION: The evaluated CBCT device provided satisfactory volume measurements. To assess volume measurements, it might be sufficient to use serial scans with a high resolution, but a low dose. This information may provide useful guidance for assessing volume measurements. PMID- 28989900 TI - Prevalence of pineal gland calcification as an incidental finding in patients referred for implant dental therapy. AB - PURPOSE: Pineal gland calcification has been proposed to play a role in the pathogenesis of Alzheimer disease. This study evaluated the prevalence and extent of pineal gland calcification in cone-beam computed tomography (CBCT) scans of patients referred for dental implant therapy who could possibly be a vulnerable group for this condition. MATERIALS AND METHODS: A retrospective evaluation of 500 CBCT scans was conducted. Scans that showed the area where the pineal gland was located were included. The scans were initially screened by a single observer to record the prevalence and extent of calcification. Six weeks following the completion of the study, another investigator randomly reviewed and selected 50 scans to investigate inter-observer variation, which was evaluated using reliability analysis statistics. The prevalence and measurements of the calcifications were reported using descriptive statistics. The chi-square test was used to compare the prevalence between males and females. RESULTS: The prevalence of pineal gland calcification was 58.8%. There was no statistically significant correlation between age and the extent of the calcification. The prevalence of calcification was 58.6% in females and 59.0% in males. The average anteroposterior measurement was 3.73+/-1.63 mm, while the average mediolateral measurement was 3.47+/-1.31 mm. The average total calcified area was 9.79+/-7.59 mm2. CONCLUSION: The prevalence of pineal gland calcification was high in patients undergoing implant therapy. While not all pineal gland calcifications lead to neurodegenerative disorders, they should be strongly considered in the presence of any symptoms as a reason to initiate further investigations. PMID- 28989902 TI - Quantitative assessment of image artifacts from root filling materials on CBCT scans made using several exposure parameters. AB - PURPOSE: To quantify artifacts from different root filling materials in cone-beam computed tomography (CBCT) images acquired using different exposure parameters. MATERIALS AND METHODS: Fifteen single-rooted teeth were scanned using 8 different exposure protocols with 3 different filling materials and once without filling material as a control group. Artifact quantification was performed by a trained observer who made measurements in the central axial slice of all acquired images in a fixed region of interest using ImageJ. Hyperdense artifacts, hypodense artifacts, and the remaining tooth area were identified, and the percentages of hyperdense and hypodense artifacts, remaining tooth area, and tooth area affected by the artifacts were calculated. Artifacts were analyzed qualitatively by 2 observers using the following scores: absence (0), moderate presence (1), and high presence (2) for hypodense halos, hypodense lines, and hyperdense lines. Two way ANOVA and the post-hoc Tukey test were used for quantitative and qualitative artifact analysis. The Dunnet test was also used for qualitative analysis. The significance level was set at P<.05. RESULTS: There were no significant interactions among the exposure parameters in the quantitative or qualitative analysis. Significant differences were observed among the studied filling materials in all quantitative analyses. In the qualitative analyses, all materials differed from the control group in terms of hypodense and hyperdense lines (P<.05). Fiberglass posts did not differ statistically from the control group in terms of hypodense halos (P>.05). CONCLUSION: Different exposure parameters did not affect the objective or subjective observations of artifacts in CBCT images; however, the filling materials used in endodontic restorations did affect both types of assessments. PMID- 28989901 TI - Analysis of the root position of the maxillary incisors in the alveolar bone using cone-beam computed tomography. AB - PURPOSE: The purpose of this study was to measure the buccal bone thickness and angulation of the maxillary incisors and to analyze the correlation between these parameters and the root position in the alveolar bone using cone-beam computed tomography (CBCT). MATERIALS AND METHODS: CBCT images of 398 maxillary central and lateral incisors from 199 patients were retrospectively reviewed. The root position in the alveolar bone was classified as buccal, middle, or palatal, and the buccal type was further classified into subtypes I, II, and III. In addition, the buccolingual inclination of the tooth and buccal bone thickness were evaluated. RESULTS: A majority of the maxillary incisors were positioned more buccally within the alveolar bone, and only 2 lateral incisors (0.5%) were positioned more palatally. The angulation of buccal subtype III was the greatest and that of the middle type was the lowest. Most of the maxillary incisors exhibited a thin facial bone wall, and the lateral incisors had a significantly thinner buccal bone than the central incisors. The buccal bone of buccal subtypes II and III was significantly thinner than that of buccal subtype I. CONCLUSION: A majority of the maxillary incisor roots were positioned close to the buccal cortical plate and had a thin buccal bone wall. Significant relationships were observed between the root position in the alveolar bone, the angulation of the tooth in the alveolar bone, and buccal bone thickness. CBCT analyses of the buccal bone and sagittal root position are recommended for the selection of the appropriate treatment approach. PMID- 28989903 TI - Optimizing the reconstruction filter in cone-beam CT to improve periodontal ligament space visualization: An in vitro study. AB - PURPOSE: Evaluation of alveolar bone is important in the diagnosis of dental diseases. The periodontal ligament space is difficult to clearly depict in cone beam computed tomography images because the reconstruction filter conditions during image processing cause image blurring, resulting in decreased spatial resolution. We examined different reconstruction filters to assess their ability to improve spatial resolution and allow for a clearer visualization of the periodontal ligament space. MATERIALS AND METHODS: Cone-beam computed tomography projections of 2 skull phantoms were reconstructed using 6 reconstruction conditions and then compared using the Thurstone paired comparison method. Physical evaluations, including the modulation transfer function and the Wiener spectrum, as well as an assessment of space visibility, were undertaken using experimental phantoms. RESULTS: Image reconstruction using a modified Shepp-Logan filter resulted in better sensory, physical, and quantitative evaluations. The reconstruction conditions substantially improved the spatial resolution and visualization of the periodontal ligament space. The difference in sensitivity was obtained by altering the reconstruction filter. CONCLUSION: Modifying the characteristics of a reconstruction filter can generate significant improvement in assessments of the periodontal ligament space. A high-frequency enhancement filter improves the visualization of thin structures and will be useful when accurate assessment of the periodontal ligament space is necessary. PMID- 28989905 TI - Digital subtraction radiography in TMJ imaging: A critique. PMID- 28989904 TI - Central giant cell lesion of the mandible in a 2-year old girl. AB - Central giant cell lesions are rare, benign, osteolytic, pseudocystic, solitary, localized lesions that are common in the skeletal structure, but less so in the maxillofacial region. Furthermore, to perform panoramic radiography and cone-beam computed tomography, it is necessary to prepare patients properly and to position their heads carefully. However, this can be difficult in pediatric patients, who may be anxious. In this report, we describe the case of a central giant cell lesion of the mandible in a 2-year-old girl that was evaluated with multidetector computed tomography. PMID- 28989907 TI - Comments on: Phenotypic and Molecular Identification of Nocardia in Brain Abscess. PMID- 28989906 TI - Abnormal regulation of extracellular matrix and adhesion molecules in corneas of patients with keratoconus. AB - AIM: To identify changes in the expression of genes coding for extracellular matrix (ECM) proteins in patients with non-inflammatory corneal disorder keratoconus (KC), patients with corneal scarring, and normal controls. MATERIALS AND METHODS: Total RNA extracted from corneal tissue of 13 KC patients, 2 patients with corneal scaring and 4 normal controls was analyzed using Human Extracellular Matrix & Adhesion Molecules Profiler PCR Array. Statistically significant changes in gene expression were identified using the Data Analysis software. RESULTS: Comparison of KC and control corneas with thresholds of 1.5 or greater fold change and a p-value of 0.05 or lower, revealed 21 differentially expressed genes, 16 genes were downregulated and 5 were upregulated. Among transcripts downregulated in KC patients we identified THBS1, ADAMTS1, SPP1, several collagens and integrins. We found TGFBI (BIGH3) gene was the most significantly upregulated transcript. CONCLUSION: Development of keratoconus results in deregulation of gene expression of extracellular matrix and adhesion molecules. CLINICAL SIGNIFICANCE: Downregulation of collagens and upregulation of TGFBI repeatedly identified in KC patients may be used as clinical markers of the disease. PMID- 28989908 TI - The Effects of Hydroxyethyl Starch 6% and Crystalloid on Volume Preloading Changes following Spinal Anesthesia. AB - BACKGROUND: Hypotension is one of the most common complications after spinal anesthesia for cesarean delivery. Normally, preloading with fluids, especially crystalloids, is used to prevention of hypotension. METHODS: In the present randomized clinical trial study, 120 parturients presenting for elective cesarean section with the American Society of Anesthesiologists Class I and II received either 15 cc normal saline or 7 cc/kg hydroxyethyl starch 6% (Voluven) fluid. Information regarding to systolic, diastolic, mean arterial pressure, and heart rate, incidence of hypotension, adverse effects, the total dose of atropine, and ephedrine were recorded in before and 3, 6, 9, 15, and 20 min after spinal anesthesia. Furthermore, Apgar score of newborn at the 1st and 5th min after birth was recorded. RESULTS: There was no significant difference in mean arterial pressure at different stages such as: Exactly after spinal and 3, 6, 15, and 20 min after spinal anesthesia between two groups (P > 0.05). Total dose of ephedrine and atropine were similar between groups (P > 0.05), respectively. There was no significant difference in Apgar score at the 1st and 5th min after birth between two groups. There were not any adverse effects of drugs in two groups. CONCLUSIONS: The results of this study show that hydroxyethyl starch 6% compared to normal saline are similar to prevent hypotension during spinal anesthesia for cesarean delivery. PMID- 28989909 TI - Evaluation of Progesterone and Ovulation-stimulating Drugs on the Glandular Epithelium and Angiogenesis in Mice. AB - BACKGROUND: Human endometrium is a dynamic tissue during the menstrual cycle can be influenced by ovarian hormones. The purpose of this study was to evaluate the endometrium angiogenesis under the influence of human menopausal gonadotropin and human chorionic gonadotropin (HMG and HCG) that stimulate ovulation and progesterone. MATERIALS AND METHODS: In this study, thirty adult female mice were randomly divided into three groups as: control, gonadotropin and gonadotropin + progesterone. The mice in the other two groups except the control group received 7.5 IU HMG and later HCG. Subsequently, the mice were placed in a cage for mating. Gonadotropin + progesterone group was administered, 1 mg/mouse progesterone in 24, 48, and 72 h interval, after HMG injection. Ninety-six hours after HMG injection, animals were sacrificed, and their uterine specimens were prepared by immunohistochemistry technique for light microscopic studies, and statistical analysis was carried out. RESULTS: Endometrium angiogenesis in control group showed that mean +/- standard deviation was 24.15 +/- 11.15, gonadotropin group was 62.50 +/- 24.16, and gonadotropin + progesterone group was 41.85 +/- 19.54. Significant difference between the control group and gonadotropin group and between the control group and gonadotropin + progesterone was observed. Statistically significant differences were observed in all groups in the endometrial angiogenesis (P < 0.05). CONCLUSION: Ovarian induction with gonadotropins and gonadotropins + progesterone could not change the morphometrically index of endometrial glandular epithelium in mice. Ovarian stimulation followed by progesterone injection could modify the angiogenesis of mice endometrium. PMID- 28989910 TI - Clinical Implications of TiGRT Algorithm for External Audit in Radiation Oncology. AB - BACKGROUND: Performing audits play an important role in quality assurance program in radiation oncology. Among different algorithms, TiGRT is one of the common application software for dose calculation. This study aimed to clinical implications of TiGRT algorithm to measure dose and compared to calculated dose delivered to the patients for a variety of cases, with and without the presence of inhomogeneities and beam modifiers. MATERIALS AND METHODS: Nonhomogeneous phantom as quality dose verification phantom, Farmer ionization chambers, and PC electrometer (Sun Nuclear, USA) as a reference class electrometer was employed throughout the audit in linear accelerators 6 and 18 MV energies (Siemens ONCOR Impression Plus, Germany). Seven test cases were performed using semi CIRS phantom. RESULTS: In homogeneous regions and simple plans for both energies, there was a good agreement between measured and treatment planning system calculated dose. Their relative error was found to be between 0.8% and 3% which is acceptable for audit, but in nonhomogeneous organs, such as lung, a few errors were observed. In complex treatment plans, when wedge or shield in the way of energy is used, the error was in the accepted criteria. In complex beam plans, the difference between measured and calculated dose was found to be 2%-3%. All differences were obtained between 0.4% and 1%. CONCLUSIONS: A good consistency was observed for the same type of energy in the homogeneous and nonhomogeneous phantom for the three-dimensional conformal field with a wedge, shield, asymmetric using the TiGRT treatment planning software in studied center. The results revealed that the national status of TPS calculations and dose delivery for 3D conformal radiotherapy was globally within acceptable standards with no major causes for concern. PMID- 28989911 TI - The Effect of Levothyroxine on Serum Levels of Interleukin 10 and Interferon gamma in Rat Model of Multiple Sclerosis. AB - BACKGROUND: There is an increase in inflammatory and a reduction in anti inflammatory cytokines in multiple sclerosis (MS). Considering the role of thyroid hormones in the development and regulation of both neural and immune systems, the aim of this study was to evaluate the effects of levothyroxine on serum concentrations of interleukin-10 (IL-10) and interferon gamma (IFN-gamma) in animal models of MS. MATERIALS AND METHODS: To induce demyelination in male Wistar rats, lysolecithin was injected into the optic chiasm. Then levothyroxine was injected intraperitoneally (20, 50, and 100 MUg/kg) for 21 days. Serum levels of cytokines were measured by enzyme-linked immunosorbent assay at 7, 14, and 21 days after that. RESULTS: The results showed that injection of lysolecithin to the optic chiasm only increased serum concentrations of IL-10 compared to the sham group (P < 0.05) at 7th day, but this increase was prevented by all doses of levothyroxine. IFN-gamma was decreased significantly (P < 0.001) 21 days after. Comparing to the sham group at all sampling time and with respect to the MS group at the days 7 and 21, levothyroxine decreased serum concentrations of IFN-gamma significantly. CONCLUSION: The results showed that thyroid hormones probably could produce protective effects against induced demyelination through affecting immune responses. PMID- 28989912 TI - Effect of Low-dose Atracurium on Laryngeal Mask Airway Insertion Conditions: A Randomized Double-blind Clinical Trial. AB - BACKGROUND: The amount of sedation and muscle relaxation of the jaw may have an impact on complications caused by laryngeal mask airway (LMA). The aim of this study is to evaluate the effect of low-dose Atracurium on conditions of insertion, complications, and hemodynamic responses to LMA insertion following induction of anesthesia with propofol, in patients undergoing cataract surgery. PATIENTS AND METHODS: In this double-blind randomized clinical trial study, 60 patients were randomly divided into two groups. Initially, the patients in the study group received 0.15 mg/kg intravenous injection of atracurium, and the patients in the control group received 2 ml of intravenous injection of normal saline, after which anesthesia in both groups were induced with midazolam, fentanyl, lidocaine, and propofol. The amount of jaw relaxation, ease of insertion, and the time needed for insertion, hemodynamic responses and complications of LMA insertion were evaluated. RESULTS: Jaw relaxation and ease of LMA insertion in the study group was significantly better than that of the control group (P = 0.02). Average time needed for LMA placement in the study group (5/06 +/- 0.52 second) was significantly lower than the control group (5/76 +/- 0.67 second) (P = 0.001). Hemodynamic response to LMA insertion was similar in both groups. Sore throat at recovery and 24 h after surgery in the control group was significantly higher than that of the study group (3/30 vs. 10/30) (P = 0.01). CONCLUSIONS: Using low doses of atracurium decreases the time needed for LMA insertion and sore throat after the operation. Atracurium also increases jaw relaxation and facilitates the placement of LMA. PMID- 28989913 TI - Efficacy Comparison of Divided and Infusion Intravenous Pantoprazole Methods after Endoscopic Therapy in Patients with Acute Gastrointestinal Bleeding. AB - BACKGROUND: Intravenous pantoprazole administration in patients with severe bleeding under urgent endoscopic therapy is effective. Furthermore, its infusion dose is useful to control bleeding; however, it is not economical. In this study, clinical outcomes and intravenous infusion of pantoprazole after endoscopic therapy plus efficacy of infusion dosage and divided doses are compared. MATERIALS AND METHODS: This prospective, comparative study conducted on 18 adult (>18 years) patients referred to Al Zahra Hospital for hematemesis and melena bleeding who underwent endoscopic treatment with pantoprazole which divided into two groups of forty patients. First group received intravenous infusion for 80 mg and 8 mg/h. The second group received intravenous infusion with divided doses as 40 mg twice daily for 3 days. Clinical outcomes such as rebleeding, duration of hospitalization, amount of blood transfused, and mortality within 3 days after endoscopic treatment were collected and analyzed by SPSS software (version 20) using independent t-test, Chi-square test, and Fisher's exact test. RESULTS: Duration of hospitalization in the pantoprazole infusion group was 5.42 +/- 4.62 days, with three patients (7.5%) having rebleeding, and in the divided pantoprazole group was 5.90 +/- 3.08 days, with four patients (10%) having rebleeding, and overall, only one person died in the divided pantoprazole group (2.5%) out of eighty patients. No significant difference was observed between two groups in terms of clinical outcomes (P > 0.05). CONCLUSION: Regarding to results, it can be stated that both methods with specified dosage had significant impact on improvement of hematemesis and melena. Furthermore, due to lower costs, low dose of pantoprazole in divided approach as 40 mg/12 h is proposed. PMID- 28989914 TI - Which Components of Metabolic Syndrome have a Greater Effect on Mortality, CVA and Myocardial Infarction, Hyperglycemia, High Blood Pressure or Both? AB - BACKGROUND: This study aims to evaluate the incidence of stroke, ischemic heart disease (IHD), and cardiovascular disease (CVD) mortality in clusters containing hypertension (HTN), clusters containing diabetes (diabetes mellitus [DM]), cluster with both HTN, DM, and cluster without HTN, DM in patients with metabolic syndrome (MetS). MATERIALS AND METHODS: The association between MetS and outcomes was examined in 2257 patients with MetS that were divided into four groups includes patients with MetS with hyperglycemia (Cluster 1), patients with MetS with HTN (Cluster 2), patients with MetS with HTN and hyperglycemia (Cluster 3) and patients with MetS without HTN and hyperglycemia (Cluster 4). To assess the risk ratio and incidence of CVA, myocardial infarction, and mortality with the use multivariate Cox proportional hazards models. RESULTS: As it shown the lowest prevalence of events was in Cluster 1 and against in Cluster 3 the prevalence of stroke with 34 (38.2%) cases and the prevalence of IHD and CVD mortality in Cluster 2 with, respectively, 168 (54.7%) and 51 patients (49%) had the most frequencies (P < 0.001), and hence that the lowest prevalence of events was seen in Cluster 1, but stroke in Cluster 3 with 34 cases (38.2%) and the prevalence of IHD and CVD mortality in Cluster 2, respectively, with 168 (54.7%) and 51 patients (49%) had the most frequencies (P < 0.001). CONCLUSION: More intensive changes in lifestyle and management protocols may be required in these patients for controlling the components of the syndrome, with the aim of preventing not only type II diabetes and CVD but also ischemic cerebrovascular events. PMID- 28989915 TI - Management of Substance Use Disorder in Military Services: A Comprehensive Approach. AB - BACKGROUND: Historically, substance misuse has been a serious problem faced by worldwide military personnel. Some research showed that military personnel have higher rates of unhealthy substance use than their age peers in the general population. These problems have serious consequences and may lead to significant military difficulties in the field of readiness, discipline, and mental or physical health. In this review, we gathered various methods for prevention, diagnosis, and treatment of substance use disorders and suggested a comprehensive plan for Iran Armed Forces to improve existing services. MATERIALS AND METHODS: This article is a narrative review study, which was carried out on 2016. A careful literature review was performed between January 1970 and April 2016 on several national and international databases. Articles were screened according to the following inclusion criteria: (1) review articles about prevention and treatment protocols, (2) executive guidance, (3) cohort articles about risk factors of addiction, and (4) randomized controlled trials about prevention or treatment of substance use disorders in army service members. After screening by title and abstract, 130 articles selected of 832 founded articles, and after quality assessment, finally, 63 articles included in the review. RESULTS: There is a necessity to manage substance use disorder through prevention, screening, and then referral to proper services for diagnosis and treatment. Urinalysis programs for screening are cost-effective and should be considered as a main method. Effective treatment includes both behavioral and pharmacological methods. CONCLUSIONS: The ideal prevention program will include multiple and mutually reinforcing evidence-based universal, selective, and indicated attempts at both the individual and environmental levels. The implementation of screening and treatment strategies needs strict rules and national guideline for the comprehensive management of substance use disorders in army. PMID- 28989916 TI - Use of progesterone supplement therapy for prevention of preterm birth: review of literatures. AB - Preterm birth (PTB) is one of the most common complications during pregnancy and it primarily accounts for neonatal mortality and numerous morbidities including long-term sequelae including cerebral palsy and developmental disability. The most effective treatment of PTB is prediction and prevention of its risks. Risk factors of PTB include history of PTB, short cervical length (CL), multiple pregnancies, ethnicity, smoking, uterine anomaly and history of curettage or cervical conization. Among these risk factors, history of PTB, and short CL are the most important predictive factors. Progesterone supplement therapy is one of the few proven effective methods to prevent PTB in women with history of spontaneous PTB and in women with short CL. There are 2 types of progesterone therapy currently used for prevention of PTB: weekly intramuscular injection of 17-alpha hydroxyprogesterone caproate and daily administration of natural micronized progesterone vaginal gel, vaginal suppository, or oral capsule. However, the efficacy of progesterone therapy to prevent PTB may vary depending on the administration route, form, dose of progesterone and indications for the treatment. This review aims to summarize the efficacy and safety of progesterone supplement therapy on prevention of PTB according to different indication, type, route, and dose of progesterone, based on the results of recent randomized trials and meta-analysis. PMID- 28989917 TI - Comparison of perinatal outcomes in late preterm birth between singleton and twin pregnancies. AB - OBJECTIVE: To determine whether late preterm twin neonates have a more favorable perinatal outcome than singleton late preterm neonates. METHODS: We studied 401 late preterm births between 34+0 and 36+6 weeks of gestation, from January 2011 to December 2014 in our institution. We compared the maternal and neonatal characteristics and perinatal outcomes between singleton and twin pregnancies. Perinatal outcomes included Apgar score, admission to the neonatal intensive care unit (NICU) or special care nursery, duration of NICU stay, and the rate of composite morbidity (antibiotic use, hypoglycemia, hypocalcemia, hyperbilirubinemia requiring phototherapy, respiratory support, and respiratory distress syndrome). RESULTS: A total of 289 neonates were in the singleton group and 112 in the twin group. The twin group showed smaller mean birth weight despite of longer gestational age at delivery. In addition, there were significant differences in the indication of delivery and cesarean section rate between the 2 groups. Overall, the risk of composite morbidity was similar between 2 groups (odds ratio, 1.4; 95% confidence interval, 0.8 to 2.4). CONCLUSION: Our findings suggest that late preterm twins do not show a more favorable outcome than singleton late preterm births. PMID- 28989918 TI - Serum beta-hCG concentration is a predictive factor for successful early medical abortion with vaginal misoprostol within 24 hours. AB - OBJECTIVE: To evaluate the predictive factors associated with the success of medical abortion by misoprostol monotherapy within 24 hours in the first trimester of pregnancy. METHODS: The records of 228 women with miscarriage up to 11 weeks of gestational age who underwent medical abortion by intravaginal misoprostol monotherapy were reviewed. Success of abortion was defined as complete expulsion of the conceptus without the need for surgical intervention. Outcomes of interest were success of abortion within 24 hours following administration of misoprostol. RESULTS: Among 222 women who continued the process of medical abortion for 24 hours, 209 (94.1%) had a successfully completed abortion. Multivariate logistic regression showed that serum beta-human chorionic gonadotropin (beta-hCG) above 40,000 mIU/mL is significantly associated with failed medical abortion within 24 hours (odds ratio [OR], 7.13; 95% confidence interval [CI], 1.60-37.32; P=0.011). The area under the receiver operating characteristic curve of beta-hCG level associated with successful abortion within 24 hours was 0.705 (95% CI, 0.63-0.77; P=0.007). Previous vaginal delivery seems to be significantly associated with successful abortion within 24 hours on univariate analysis (P=0.037), but the association was lost in multivariate analysis. CONCLUSION: Misoprostol monotherapy has a high success rate for first trimester abortion. Women with serum beta-hCG less than 40,000 mIU/mL are likely to achieve a successful abortion within 24 hours after intravaginal administration of misoprostol. PMID- 28989919 TI - The efficacy and safety of pegylated liposomal doxorubicin monotherapy and combination therapy with carboplatin in Korean patients with recurrent ovarian, fallopian tube, or primary peritoneal cancer: a single-institution experience. AB - OBJECTIVE: This study aimed to evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD) with or without carboplatin in Korean patients with recurrent ovarian cancer (ROC), fallopian tube, or primary peritoneal cancer. METHODS: This retrospective study included 52 patients with ROC, fallopian tube, or primary peritoneal cancer who received PLD (50 mg/m2) between 1st December 2014 and 31th July 2016. RESULTS: The mean number of chemotherapy cycles was 3.8 (range, 2 to 9) in the PLD monotherapy group and 7 (range, 2 to 13) in the PLD combined with carboplatin (PLD-C) group. In overall response rates and clinical beneficial rates, PLD monotherapy group shows 5.0% and 17.5%, and PLD-C group shows 33.3% and 75.0%. The mean progression-free survival (PFS) was 5 and 13 months in the PLD monotherapy and PLD-C groups, respectively. At 6 months after treatment initiation, absence of disease progression was confirmed in 6 (15%) and 10 (83.3%) patients in the PLD monotherapy and PLD-C groups. Hematological adverse events (e.g., neutropenia and thrombocytopenia) were more common in the PLD-C group (P<0.001, P=0.004). The incidence of anemia and non-hematological adverse events, including mucositis, hand-foot syndrome, and allergic reactions, was similar in both groups. CONCLUSION: This study demonstrated the efficacy and safety of PLD monotherapy and PLD-C combination in Korean patients with ROC. This study would be helpful to consider the degree of worry about side effects and treatment expectations after treatment. Further retrospective studies with larger samples are required to confirm the efficacy of PLD monotherapy in Asian patients with platinum-resistant ROC. PMID- 28989920 TI - Nomogram predicting risk of lymphocele in gynecologic cancer patients undergoing pelvic lymph node dissection. AB - OBJECTIVE: The purpose of this study is to estimate the risk of postoperative lymphocele development after lymphadenectomy in gynecologic cancer patients through establishing a nomogram. METHODS: We retrospectively reviewed 371 consecutive gynecologic cancer patients undergoing lymphadenectomy between 2009 and 2014. Association of the development of postoperative lymphocele with clinical characteristics was evaluated in univariate and multivariate regression analyses. Nomograms were built based on the data of multivariate analysis using R software. RESULTS: Mean age at the operation was 50.8+/-11.1 years. Postoperative lymphocele was found in 70 (18.9%) patients. Of them, 22 (31.4%) had complicated one. Multivariate analysis revealed that hypertension (hazard ratio [HR], 3.0; 95% confidence interval [CI], 1.5 to 6.0; P=0.003), open surgery (HR, 3.2; 95% CI, 1.4 to 7.1; P=0.004), retrieved lymph nodes (LNs) >21 (HR, 1.8; 95% CI, 1.0 to 3.3; P=0.042), and no use of intermittent pneumatic compression (HR, 2.7; 95% CI, 1.0 to 7.2; P=0.047) were independent risk factors for the development of postoperative lymphocele. The nomogram appeared to be accurate and predicted the lymphocele development better than chance (concordance index, 0.754). For complicated lymphoceles, most variables which have shown significant association with general lymphocele lost the statistical significance, except hypertension (P=0.011) and mean number of retrieved LNs (29.5 vs. 21.1; P=0.001). A nomogram for complicated lymphocele showed similar predictive accuracy (concordance index, 0.727). CONCLUSION: We developed a nomogram to predict the risk of lymphocele in gynecologic cancer patients on the basis of readily obtained clinical variables. External validation of this nomogram in different group of patients is needed. PMID- 28989921 TI - Gonadotropin releasing hormone antagonist administration for treatment of early type severe ovarian hyperstimulation syndrome: a case series. AB - OBJECTIVE: To report an efficacy of gonadotropin releasing hormone (GnRH) antagonist administration after freezing of all embryos for treatment of early type ovarian hyperstimulation syndrome (OHSS). METHODS: In 10 women who developed fulminant early type OHSS after freezing of all embryos, GnRH antagonist (cetrorelix 0.25 mg per day) was started at the time of hospitalization and continued for 2 to 4 days. Fluid therapy and drainage of ascites was performed as usual. RESULTS: Early type OHSS was successfully treated without any complication. At hospitalization, the median (95% confidence interval [CI]) of the right and the left ovarian diameter was 10.0 cm (7.6 to 12.9 cm) and 8.5 cm (7.5 to 12.6 cm). After completion of GnRH antagonist administration, it was decreased to 7.4 cm (6.2 to 10.7 cm) (P=0.028) and 7.8 cm (5.7 to 12.2 cm) (P=0.116), respectively. The median duration of hospital stay was 6 days (3 to 11 days). Trans-abdominal drainage of ascites was performed in 2 women and drainage of ascites by percutaneous indwelling catheter was performed in 4 women. No side effect of GnRH antagonist was noted. CONCLUSION: GnRH antagonist administration appears to be safe and effective for women with fulminant early type OHSS after freezing all embryos. Optimal dose or duration of GnRH antagonist should be further determined. PMID- 28989922 TI - Port site infiltration of local anesthetic after laparoendoscopic single site surgery for benign adnexal disease. AB - OBJECTIVE: To determine whether local bupivacaine injection into the incision site after gynecologic laparoendoscopic single site surgery (LESS) improves postoperative pain. METHODS: This prospective cohort study included consecutive 158 patients who had LESS for benign adnexal disease from March 2013 to December 2015. Chronologically, 82 patients (March 2013 to August 2014) received no bupivacaine (group 1) and 76 (August 2014 to December 2015) received a bupivacaine block (group 2). For group 2, 10 mL 0.25% bupivacaine was injected into the 20 mm-incision site through all preperitoneal layers after LESS completion. Primary outcome is postoperative pain score using the visual analog scale (VAS). RESULTS: There was no difference in clinicopathological characteristics between the groups. Operating time (expressed as median [range], 92 [55-222] vs. 100 [50-185] minutes, P=0.137) and estimated blood loss (50 [30 1,500] vs. 125 [30-1,000] mL, P=0.482) were similar between the groups. Post surgical VAS pain scores after 3 hours (3.5 [2-6] vs. 3.5 [2-5], P=0.478), 6 to 8 hours (3.5 [2-6] vs. 3 [1-8], P=0.478), and 16 to 24 hours (3 [2-4] vs. 3 [1-7], P=0.664) did not differ between groups. CONCLUSION: Bupivacaine injection into the trocar site did not improve postoperative pain after LESS. Randomized trials are needed to evaluate the benefits of local bupivacaine anesthetic for postoperative pain reduction. PMID- 28989923 TI - Preoperative diagnostic clues to ovarian pregnancy: retrospective chart review of women with ovarian and tubal pregnancy. AB - OBJECTIVE: To analyze the preoperative diagnostic clues to ovarian pregnancy (OP). METHODS: This study conducted a retrospective chart review of 23 patients with OP and 46 patients with tubal pregnancy (TP) from October 1, 2003 to September 31, 2016 in Hanyang University Hospital. RESULTS: There were no significant differences in demographic and clinical characteristics between the two groups. The presence of an ectopic gestational sac and hemoperitoneum was significantly higher in the TP group (13.0% vs. 95.7%, P=0.000; 13.0% vs. 54.3%, P=0.001, respectively) in preoperative ultrasonogram. The OP group had more ruptured ectopic gestational sacs than the TP group (73.9% vs. 45.7%, P=0.039) in surgical findings. CONCLUSION: For the patients in whom a gestational sac is not detected in the uterus or the fallopian tubes, it is important to be aware of the possibility of OP and rupture of an ovarian gestational sac to promote early diagnosis and surgical intervention. PMID- 28989924 TI - Epithelial ovarian tumors in a premenarchal girl: a rare case report. AB - Ovarian tumors are relatively uncommon in paediatric age group and mostly occur in the period after menarche and are extremely rare prior to menarche. However, in children and adolescent, the epithelial ovarian tumors account approximately 10% to 28% of all ovarian tumors. In the present case, the patient was presented with abdominal pain for 1 day and no mass was felt on physical examination. Contrast-enhance computed tomography abdomen and pelvis showed a left ovarian cystic mass measuring 7.3*5.1 cm in size and unilateral oophorectomy was done. Tumor shows multiloculated cysts of varying sizes filled with mucinous fluid. Cysts were lined by tall columnar epithelial cells and show predominantly periodic acid-Schiff positive neutral mucin favouring benign nature of lesion. We present this case due to its uncommon age of presentation and the patient was premenarchal girl. PMID- 28989925 TI - Genital tract cavernous hemangioma as a rare cause of postpartum hemorrhage. AB - Cavernous hemangiomas rarely involve the female genital tract. It is difficult to identify vascular malformations when these lesions are concealed in the vagina or deep vulva area. We present a rare case of vaginal cavernous hemangioma in a 30 year-old primiparous woman with an early severe postpartum hemorrhage (PPH) and delayed continuous bleeding from the episiotomy site. She was treated successfully with transarterial embolization of the left vaginal artery. To our knowledge, this is the first reported case of PPH caused by rupture of a vaginal hemangioma during vaginal delivery in English literature. PMID- 28989926 TI - BRCA1-mutated ovarian cancer with skin metastasis: a case report. AB - The major risk factor for ovarian cancer (OC) is mutation of the BRCA1 or BRCA2 DNA mismatch repair genes, which occurs in approximately 10% of OC cases. Most previous studies have demonstrated that BRCA1- and BRCA2-mutated OCs are associated with better prognosis than sporadic OCs. However, information about the patterns and clinical course of the metastatic spread of BRCA-mutated OCs is limited. Herein, we describe a case of OC with a BRCA1 mutation and skin metastases in a 49-year-old patient, which to the best of our knowledge has not been reported previously. PMID- 28989927 TI - Metastatic uterine cancer looking as cervical fibroid in recurrent breast cancer woman: a case report. AB - Metastasis to the female genital tract from extragenital primary cancer is uncommon. In this case, a 46-year-old woman was diagnosed with invasive lobular carcinoma of the left breast in 2011. She had left breast conserving surgery, chemotherapy, radiation, and hormonal therapy (gosereline and tamoxifen). However, she developed menorrhagia after interruption of hormonal therapy and incidentally, the ultrasonogram of her pelvis showed a solid, large mass in the cervix. It looked like leiomyoma. Because of massive vaginal bleeding requiring multiple blood transfusions, she underwent total hysterectomy with bilateral salpingo-oophorectomy. Unexpectedly, however, histopathological examination revealed metastatic carcinoma, consistent with breast origin.The metastatic tumor involved the uterine corpus with spreading to the endocervix, left ovary, and multiple lymphovascular invasion was present. We described the rarity and risk of metastatic uterine cancer in patient with history of malignant tumor treatment. PMID- 28989928 TI - Estrogen-induced acute pancreatitis: A case report and literature review. AB - Estrogens are commonly used in gynecologic area, such as oral contraception, hormone replacement therapy, and in vitro fertilization-embryo transfer. Although estrogen is a common cause of acute drug-induced pancreatitis, there has been paucity of report in Korea. Clinical course of estrogen-induced acute pancreatitis is usually mild to moderate, but fetal case can occur. In addition, there can be a latency from the first administration to the symptom. Therefore, physicians should consider the possibility of the disease when a woman taking estrogen or previous history of taking estrogen presents with acute abdominal pain. Here, we report a case of estrogen-induced acute pancreatitis that occurred during the preparation for embryo transfer. PMID- 28989929 TI - Delayed intestinal perforation and vertebral osteomyelitis after high-intensity focused ultrasound treatment for uterine leiomyoma. AB - High-intensity focused ultrasound (HIFU) is a non-invasive uterine fibroid treatment option for patients who want to preserve fertility. However, according to several reports regarding ablation of solid tumors by HIFU, there are rare complications in patients with uterine leiomyomas, and overall data are still insufficient. Here, we report rare and major complications of HIFU, such as delayed intestinal perforation, uterine perforation with recto-uterine fistula, and osteomyelitis 29 days after the HIFU procedure to treat multiple myomas. Thus, we present a very serious case resulting from HIFU treatment of uterine fibroids and a review of the literature. PMID- 28989930 TI - A case report of angioleiomyoma of uterus. AB - Angioleiomyoma (AL) is a very rare benign tumor that originates from smooth muscle cells and has thick walled vessels. It may be found throughout the body but more frequently occurs in the lower extremities and rarely develops in the head and other parts of the body. This paper presents a case report of giant AL detected in a 33-year-old woman who complained of severe anemia, menorrhagia, and palpable lower abdominal mass. The patient underwent myomectomy and was diagnosed with AL based on the pathological report of mass. The effective treatment for AL is either simple hysterectomy or angiomyomectomy depending on the patient's desire to preserve fertility and symptom. PMID- 28989931 TI - The Impact of Historical and Current Loss on Chronic Illness: Perceptions of Crow (Apsaalooke) People. AB - The purpose of this research was to gain a better understanding of perceptions about the impact of historical and current loss on Apsaalooke (Crow) people acquiring and coping with chronic illness. This study took a qualitative phenomenological approach by interviewing community members with chronic illness in order to gain insight into their perceptions and experiences. Participants emphasized 10 areas of impact of historical and current loss: the link between mental health and physical health/health behaviors; resiliency and strengths; connection and isolation; importance of language and language loss; changes in cultural knowledge and practices; diet; grieving; racism and discrimination; changes in land use and ownership; and boarding schools. The findings from this research are being used to develop a chronic illness self-care management program for Crow people. PMID- 28989932 TI - MUTATIONS IN LIVER X RECEPTOR ALPHA THAT IMPAIR DIMERIZATION AND LIGAND DEPENDENT TRANSACTIVATION. AB - Liver X receptor alpha (LXRalpha) is crucial for the maintenance of lipid and cholesterol homeostasis. Ligand binding and dimerization with retinoid X receptor (RXR) or peroxisome proliferator-activated receptor (PPAR) is required for forming active DNA binding complexes leading to gene regulation. Structure based prediction and solvent accessibility of LXRalpha LBD shows that residues H383, E387, H390, L414, and R415 which are located in helices 9 and 10 may be critical for mediating protein-protein interactions. In this study, LXRalpha interface residues were individually mutated to determine their effects on ligand binding, protein-protein association, subcellular localization, and transactivation activity. LXRalpha L414R and R415A lacked binding to T-0901317, but retained binding to 25-Hydroxycholesterol. In vitro assay and a cell based assay demonstrated that LXRalpha L414R was specifically impaired for interactions with RXRalpha but not PPARalpha suggesting that charge reversal at the interface provides selectivity to LXRalpha dimerization. Furthermore, binding of LXRalpha L414R or R415A with PPARalpha exhibited minimal conformational changes in the dimer secondary structure. Interestingly, all LXRalpha mutants exhibited lower levels of ligand dependent luciferase activity driven by the SREBP-1c or ApoA1 promoter. Taken together, our data demonstrates that intact hydrophobic interactions and salt bridges at the interface mediate efficient ligand-dependent transactivation activities. PMID- 28989933 TI - Spontaneous Left Main and Right Coronary Artery Spasm in a Patient With Vasospastic Angina. AB - Coronary spasm is a well-documented, though rare, condition that can mimic myocardial infarction and is usually found in only a single vessel during an event. We describe the case of a 43-year-old male with past medical history of hypertension, hyperlipidemia, tobacco abuse, and with no known coronary disease. The patient developed chest pain 3 days postadmission for primary diagnosis of psychiatric disorder. The patient had a positive stress study with moderate reversible ischemia in the anterolateral region. A subsequent coronary angiography was performed that revealed significant left main coronary obstruction with TIMI I (thrombolysis in myocardial infarction) flow. This pattern was also present in the proximal right coronary artery. Both stenoses were relieved with intracoronary nitroglycerin, revealing no significant obstructive disease and TIMI III flow. The patient was started on dihydropyridine calcium channel blocker and counseled against smoking without recurrence of angina. PMID- 28989934 TI - Takotsubo Cardiomyopathy With a Rapidly Resolved Left Ventricular Thrombus. AB - This article presents the case of a 53-year-old man who presented with acute right superficial femoral and popliteal arterial thrombosis for which he underwent an emergent uncomplicated thrombectomy. He denied preceding cardiovascular or neurologic symptomatology and had no history of coronary or peripheral arterial disease, trauma, hypercoagulability, or malignancy. However, he reported having several days of intense emotional stress prior to presentation. His cardiac exam was normal, his electrocardiogram showed normal sinus rhythm and nonspecific ST-T wave abnormalities, and his troponin levels were normal. Transthoracic echocardiography (TTE) revealed a large (2.4 * 2 cm) apical left ventricle (LV) thrombus, LV apical akinesis, and LV ejection fraction of 40% to 45%. Coronary angiography revealed only luminal irregularities. A repeat TTE performed 3 days after initiating unfractionated heparin revealed complete resolution of the LV thrombus. The patient had an uneventful clinical course and was discharged home in stable condition on oral anticoagulants. The lower incidence of LV thrombus in takotsubo cardiomyopathy (TC) of 1.3% in comparison to 4% to 8% in acute myocardial infarction due to coronary artery disease in the current era of early reperfusion may be explained by the lower extent of ischemic myocardial necrosis associated with TC. This case suggests that the lower extent of myocardial necrosis in TC may also lead to faster resolution of LV thrombus. Therefore, earlier follow-up with TTE (within 2 weeks) and shorter duration of anticoagulation (<3 months) may be considered in patients with TC complicated by LV thrombus formation with or without systemic embolism. PMID- 28989935 TI - Pathologic Findings of Chronic PML-IRIS in a Patient with Prolonged PML Survival Following Natalizumab Treatment. AB - Immune reconstitution inflammatory syndrome (IRIS) is a common complication during treatment for natalizumab-associated progressive multifocal leukoencephalopathy (PML). Although severe IRIS can result in acute worsening of disability and is associated with poor prognosis, effective immune reconstitution may account for the high survival rate of this cohort of PML patients. We present pathological evidence of chronic IRIS 3.5 years after diagnosis with natalizumab associated PML. Our case showed that the IRIS initially developed after plasma exchange therapy and resolved clinically and radiologically following a combination treatment with corticosteroids, maraviroc, and cidofovir. Autopsy 3.5 years later revealed evidence of grey-white matter junction demyelinating lesions characteristic of PML and perivascular leukocyte infiltrates predominated by CD8+ T-lymphocytes, and polymerase chain reaction analysis demonstrated the presence of JC viral DNA in this tissue, indicative of persistent PML-IRIS. While clinical symptoms of PML-IRIS typically stabilize within 6 months, our case report suggests that prolonged low-grade inflammation may persist in some patients. Better assays are needed to determine the prevalence of prolonged low-grade IRIS among PML survivors. PMID- 28989936 TI - Closing the Data Loop: An Integrated Open Access Analysis Platform for the MIMIC Database. AB - We describe a new model for collaborative access, exploration, and analyses of the Medical Information Mart for Intensive Care - III (MIMIC III) database for translational clinical research. The proposed model addresses the significant disconnect between data collection at the point of care and translational clinical research. It addresses problems of data integration, preprocessing, normalization, analyses (along with associated compute back-end), and visualization. The proposed platform is general, and can be easily adapted to other databases. The pre-packaged analyses toolkit is easily extensible, and allows for multi-language support. The platform can be easily federated, mirrored at other locations, and supports a RESTful API for service composition and scaling. PMID- 28989937 TI - Comparison of 2 Radiographic Techniques for Measurement of Tibiofemoral Joint Space Width. AB - BACKGROUND: No consensus is available regarding the best method for measuring tibiofemoral joint space width (JSW) on radiographs to quantify joint changes after injury. Studies that track articular cartilage thickness after injury frequently use patients' uninjured contralateral knees as controls, although the literature supporting this comparison is limited. PURPOSE: (1) To compare JSW measurements using 2 established measurement techniques in healthy control participants and (2) to determine whether the mean JSW of the uninjured contralateral knee in a cohort with anterior cruciate ligament (ACL) reconstruction is different from that obtained from a true control population. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 2. METHODS: Medial and lateral JSWs were measured on standardized, bilateral, semiflexed metatarsophalangeal positioning, posteroanterior radiographs of 60 healthy individuals (26 females; mean +/- SD age, 25 +/- 6.2 years; no history of knee injury) via 2 published techniques: a computerized surface-delineation method (surface-fit method) and a manual digitization method (midpoint method). Bland Altman method was used to examine the agreement between JSW measurements obtained with the 2 methods and to examine the agreement between measurements obtained on left and right knees within a participant for each measurement method. Within- and between-participant variance components and intraclass correlation coefficients (ICCs) were computed for JSW measurements corresponding to each method. Two-sample t tests were used to compare the surface-fit method measurements of mean JSW of the true control group (n = 60) with the previously published mean JSW measurements from the Multicenter Orthopaedics Outcomes Network (MOON) nested cohort of 262 contralateral uninjured knees 2 to 3 years after ACL reconstruction. RESULTS: For JSW in the medial compartment, the surface fit method had lower within-participant interknee variability (sigma2within, 0.064; 95% CI, 0.04-0.09) compared with the midpoint method (sigma2within, 0.28; 95% CI, 0.20-0.43) and a higher ICC (0.93 vs 0.65; P < .001). Lateral JSW values were similar for the surface-fit method (sigma2within, 0.27; 95% CI, 0.18-0.43) and the midpoint method (sigma2within, 0.20; 95% CI, 0.14-0.31), with ICCs of 0.75 and 0.77, respectively (P = .80). With the surface-fit method, mean JSW measurements of the medial and lateral compartments of a control population were not significantly different from the contralateral uninjured knees of patients after ACL reconstruction. CONCLUSION: For measuring medial JSW, the surface-fit method was less variable across knees within a participant than the midpoint method, as evidenced by larger ICCs and lower interknee variability. For measuring lateral JSW, the 2 methods were similar. The JSW measurements of uninjured contralateral knees of patients with ACL reconstruction at 2 to 3 years postsurgery were not significantly different from those of a cohort of healthy control participants. Future work should be performed to demonstrate the validity of these methods for documenting change over time in the ACL-reconstructed knee. PMID- 28989938 TI - Position Statement From the Australian Knee Society on Arthroscopic Surgery of the Knee, Including Reference to the Presence of Osteoarthritis or Degenerative Joint Disease: Updated October 2016. PMID- 28989940 TI - Corrigendum. AB - [This corrects the article DOI: 10.1177/2325967117723108.]. PMID- 28989939 TI - Recovery of Shoulder Rotational Muscle Strength After Arthroscopic Bankart Repair. AB - BACKGROUND: Shoulder rotational muscles act as dynamic stabilizers of the glenohumeral joint, and the recovery of muscle strength plays an important role in stabilizing the joint during postoperative rehabilitation. However, temporal changes in muscle strength after arthroscopic Bankart repair have not been clarified. PURPOSE: To better understand the temporal recovery of shoulder rotational muscle strength after arthroscopic Bankart repair. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Isokinetic concentric shoulder rotational muscle strength was evaluated in 50 patients who were diagnosed with recurrent dislocations of the glenohumeral joint and treated with arthroscopic Bankart repair. RESULTS: The mean peak torque/weight and total work were reduced significantly at 1.5 months after surgery (P < .0001) and returned to preoperative levels by 6 months for external rotation and 4.5 months for internal rotation. The contralateral peak torque ratios reached preoperative levels by 6 months after surgery. The ipsilateral peak torque ratios were reduced between 1.5 and 3 months after surgery and returned to preoperative levels at 6 months for external rotation and 4.5 months for internal rotation. CONCLUSION: Isokinetic shoulder rotational muscle strength after arthroscopic Bankart repair recovered to preoperative levels by 6 months for external rotation and 4.5 months for internal rotation. PMID- 28989941 TI - Resting-state networks do not determine cognitive function networks: a commentary on Campbell and Schacter (2016). PMID- 28989943 TI - Is current irrigation sustainable in the United States? An integrated assessment of climate change impact on water resources and irrigated crop yields. AB - While climate change impacts on crop yields has been extensively studied, estimating the impact of water shortages on irrigated crop yields is challenging because the water resources management system is complex. To investigate this issue, we integrate a crop yield reduction module and a water resources model into the MIT Integrated Global System Modeling framework, an integrated assessment model linking a global economic model to an Earth system model. We assess the effects of climate and socioeconomic changes on water availability for irrigation in the U.S. as well as subsequent impacts on crop yields by 2050, while accounting for climate change projection uncertainty. We find that climate and socioeconomic changes will increase water shortages and strongly reduce irrigated yields for specific crops (i.e., cotton and forage), or in specific regions (i.e., the Southwest) where irrigation is not sustainable. Crop modeling studies that do not represent changes in irrigation availability can thus be misleading. Yet, since the most water-stressed basins represent a relatively small share of U.S. irrigated areas, the overall reduction in U.S. crop yields is small. The response of crop yields to climate change and water stress also suggests that some level of adaptation will be feasible, like relocating croplands to regions with sustainable irrigation or switching to less irrigation intensive crops. Finally, additional simulations show that greenhouse gas (GHG) mitigation can alleviate the effect of water stress on irrigated crop yields, enough to offset the reduced CO2 fertilization effect compared to an unconstrained GHG emission scenario. PMID- 28989942 TI - Diagnosing phosphorus limitations in natural terrestrial ecosystems in carbon cycle models. AB - Most of the Earth System Models (ESMs) project increases in net primary productivity (NPP) and terrestrial carbon (C) storage during the 21st century. Despite empirical evidence that limited availability of phosphorus (P) may limit the response of NPP to increasing atmospheric CO2, none of the ESMs used in the previous Intergovernmental Panel on Climate Change assessment accounted for P limitation. We diagnosed from ESM simulations the amount of P need to support increases in carbon uptake by natural ecosystems using two approaches: the demand derived from (1) changes in C stocks and (2) changes in NPP. The C stock-based additional P demand was estimated to range between -31 and 193 Tg P and between 89 and 262 Tg P for Representative Concentration Pathway (RCP) 2.6 and RCP8.5, respectively, with negative values indicating a P surplus. The NPP-based demand, which takes ecosystem P recycling into account, results in a significantly higher P demand of 648-1606 Tg P for RCP2.6 and 924-2110 Tg P for RCP8.5. We found that the P demand is sensitive to the turnover of P in decomposing plant material, explaining the large differences between the NPP-based demand and C stock-based demand. The discrepancy between diagnosed P demand and actual P availability (potential P deficit) depends mainly on the assumptions about availability of the different soil P forms. Overall, future P limitation strongly depends on both soil P availability and P recycling on ecosystem scale. PMID- 28989944 TI - Association of Dietary Factors with Progression of AA in Stroke/TIA Patients. AB - OBJECTIVE: To investigate the effect of dietary factors such as calorie intake and dietary fats on the progression of aortic arch atheroma (AA). BACKGROUND: In stroke/TIA patients, progression of AA is associated with recurrent vascular events. DESIGN/METHODS: Consecutive patients with measurable (>1 mm) AA atheroma on baseline transesophageal echocardiogram (TEE) evaluation consented to a protocol mandated follow-up TEE at 12 months. Patients that had adequate paired AA images were assessed for progression, defined as Delta >= 1 grade worsening (based on plaque thickness over 12 months). Stroke risk factors and fasting lipid profile were assessed at baseline. The patient's nutritional intake was measured at baseline using the Gladys Block Food Frequency Questionnaire. RESULTS: One hundred-nine patients (70 strokes, 33 TIAs) had sequential TEEs, of whom 27% (N=30) progressed and 73% (N=79) did not. Patients with progression had higher daily calorie (1778 +/- 623 vs. 1378 +/- 406 Calories, p=0.008), fat (76 +/- 33 vs. 52 +/- 23 grams, p=0.0002), carbohydrate (208 +/- 78 vs. 169 +/- 57 grams, p=0.01) and protein (73 +/- 26 vs. 57 +/- 21 grams, p=0.005) intake. On Further analysis among different fats showed a higher consumption of saturated fats (25 +/- 12 vs. 17 +/-8 grams, p=0.00051) as well as unsaturated fats (44 +/- 20 vs. 30 +/- 13 grams, p=0.002). These differences remained significant after we adjusted for the medication use. However the significance of these differences was attenuated after adjusting for the calorie intake. Cholesterol consumption did not differ between the progression and no-progression group (262 +/- 125 vs. 213 +/- 149 mg, p=0.2). CONCLUSIONS/RELEVANCE: Calorie intake plays a significant role in the progression of AA. Further studies are needed to confirm these findings and determine the specific dietary modifications that may prevent AA progression and associated recurrent vascular events. PMID- 28989945 TI - The cardiac regenerative potential of myoblasts remains limited despite improving their survival via antioxidant treatment. AB - INTRODUCTION: Since myoblasts have been limited by poor cell survival after cellular myoplasty, the major goal of the current study was to determine whether improving myoblast survival with an antioxidant could improve cardiac function after the transplantation of the myoblasts into an acute myocardial infarction. BACKGROUND: We previously demonstrated that early myogenic progenitors such as muscle-derived stem cells (MDSCs) exhibited superior cell survival and improved cardiac repair after transplantation into infarcted hearts compared to myoblasts, which we partially attributed to MDSC's higher antioxidant levels. AIM: To determine if antioxidant treatment could increase myoblast survival, subsequently improving cardiac function after myoblast transplantation into infarcted hearts. MATERIALS AND METHODS: Myoblasts were pre-treated with the antioxidant N acetylcysteine (NAC) or the glutathione depleter, diethyl maleate (DEM), and injected into infarcted murine hearts. Regenerative potential was monitored by cell survival and cardiac function. RESULTS: At early time points, hearts injected with NAC-treated myoblasts exhibited increased donor cell survival, greater cell proliferation, and decreased cellular apoptosis, compared to untreated myoblasts. NAC-treated myoblasts significantly improved cardiac contractility, reduced fibrosis, and increased vascular density compared to DEM treated myoblasts, but compared to untreated myoblasts, no difference was noted. DISCUSSION: While early survival of myoblasts transplanted into infarcted hearts was augmented by NAC pre-treatment, cardiac function remained unchanged compared to non-treated myoblasts. CONCLUSION: Despite improving cell survival with NAC treated myoblast transplantation in a MI heart, cardiac function remained similar to untreated myoblasts. These results suggest that the reduced cardiac regenerative potential of myoblasts, when compared to MDSCs, is not only attributable to cell survival but is probably also related to the secretion of paracrine factors by the MDSCs. PMID- 28989946 TI - Tumor-targeted costimulation by using bi-specific aptamers. AB - Aptamers are chemically synthesized oligonucleotides that can be easily engineered for cancer immunotherapy use. So far, most of the therapeutic aptamers described are antagonistic and block the function of a receptor or its soluble ligand. Recently, aptamers have been modified to act as agonists by multimerization, with a direct application in cancer immunotherapy. Several agonistic aptamers against costimulatory receptors have been described. However, systemic costimulation, though potentially a very potent antitumor immune strategy, is not devoid of auto-inflammatory side effects. In a quest to reduce toxicity and improve efficacy - reducing the therapeutic index - the first bi specific aptamers to target the costimulatory ligand to the tumor have been described, showing very promising results in different preclinical tumor models. PMID- 28989947 TI - Proton Therapy for Vaginal Reirradiation. AB - Primary or recurrent gynecologic cancers in operable patients with a history of prior pelvic radiation are typically treated with surgery based on the risk of late toxicities historically associated with reirradiation. A number of studies have demonstrated that, compared with conventional radiation therapy (RT) using photons, proton therapy (PT) offers dosimetric advantages for patients with gynecologic cancers by reducing radiation dose to healthy tissues. Thereby, we expect that, in appropriately selected cases, PT may reduce long-term treatment related morbidities without compromising treatment efficacy. Herein, we describe the treatment planning, technique, and long-term follow-up of a patient who was treated with PT for a primary vaginal carcinoma nearly 30 years after a prior course of pelvic RT. Using this case, we illustrate the utility and advantages of PT in the treatment of cancers that occur at less favorable sites, adjacent to normal structures with low radiation tolerance, or in paients with a history of prior irradiation. Additionally, we provide a brief discussion and review of literature of prior case series of pelvic reirradiation, illustrating the value of identifying treatment approaches that can reduce treatment-related morbidities, particularly late treatment toxicities. PMID- 28989948 TI - Morbidity in <=1500-Gram Births in Spain, 1993-2011: Study of a Sample of 1200 Cases. AB - Background and Objective. Preterm birth has a major impact on growth, and very preterm birth is associated with disabilities in numerous developmental domains. This article describes and quantifies morbidities in a sample of 1200 <=1500-g births in Spain between 1993 and 2011 based on parent information, and it highlights several variables that influence these morbidities. Methods. Multiple method surveys using computer-assisted telephones interviewing and computer assisted web interviewing methods. Sample design was intentional. Most subjects were contacted via their referral hospitals. Data collection was done from April 2013 to June 2014. Prior to the survey, extensive qualitative fieldwork was conducted, including nonparticipant observation in neonatal units and the design and analysis of discussion groups and interviews with professionals and families, including preterm adolescents. Results. A total of 44.2% of the sample were experiencing morbidity (mean: 1.788 morbidities per child). The most prevalent types were learning difficulties (34.4%) and attention deficit/hyperactivity disorder (31.5%). The most influential variables were male gender, age, lower birthweight, private hospital admission for birth, scarcity of health resources in the family's residential area, non-Spanish maternal birthplace, and emotional distress in the primary carer. Conclusions. Overall, the total percentage of very low birth weight children with morbidities has decreased moderately between 1993 and 2011, thanks to major socio-sanitary improvements during this period. Biological and medical variables, rather than family factors, explain more accurately the presence of morbidities in children with birth weight <=1500 g. PMID- 28989949 TI - Promising Themes for Antismoking Campaigns Targeting Youth and Young Adults. AB - OBJECTIVES: Behavior change campaigns typically try to change beliefs that influence behaviors, with targeted beliefs comprising the campaign theme. We present an empirical approach for choosing among a large number of potential themes, and results from the implementation of this approach for campaigns aimed at 4 behavioral targets: (1) preventing smoking initiation among youth, and (2) preventing initiation, (3) stopping progression to daily smoking and (4) encouraging cessation among young adults. METHODS: An online survey of 13- to 17 year-olds and 18- to 25-year-olds in the United States (US), in which 20 potential campaign themes were represented by 154 beliefs. For each behavioral target, themes were ranked based on the strength of belief-intention and belief behavior associations and size of the population not already endorsing the beliefs. RESULTS: The most promising themes varied across behavioral targets but 3 were consistently promising: consequences of smoking for mood, social acceptance and social popularity. CONCLUSIONS: Using a robust and systematic approach, this study provides campaign developers with empirical data to inform their selection of promising themes. Findings related to the campaign to prevent initiation among youth informed the development of the US Food and Drug Administration's "The Real Cost" campaign. PMID- 28989950 TI - Surveillance of Nicotine and pH in Cigarette and Cigar Filler. AB - OBJECTIVE: We examined differences between nicotine concentrations and pH in cigarette and cigar tobacco filler. METHODS: Nicotine and pH levels for 50 cigarette and 75 cigar brands were measured. Non-mentholated and mentholated cigarette products were included in the analysis along with several cigar types as identified by the manufacturer: large cigars, pipe tobacco cigars, cigarillos, mini cigarillos, and little cigars. RESULTS: There were significant differences found between pH and nicotine for cigarette and cigar tobacco products. Mean nicotine concentrations in cigarettes (19.2 mg/g) and large cigars (15.4 mg/g) were higher than the other cigars types, especially the pipe tobacco cigars (8.79 mg/g). The mean pH for cigarettes was pH 5.46. Large cigars had the highest mean pH value (pH 6.10) and pipe tobacco cigars had the lowest (pH 5.05). CONCLUSIONS: Although cigarettes are the most common combustible tobacco product used worldwide, cigar use remains popular. Our research provides a means to investigate the possibility of distinguishing the 2 tobacco product types and offers information on nicotine and pH across a wide range of cigarette and cigar varieties that may be beneficial to help establish tobacco policies and regulations across product types. PMID- 28989951 TI - Current Ability of Multiparametric Prostate Magnetic Resonance Imaging and Targeted Biopsy to Improve the Detection of Prostate Cancer. AB - INTRODUCTION: Recent advancements in imaging technology have significantly increased the diagnostic accuracy of magnetic resonance imaging for prostate cancer. However, tissue diagnosis and grading remain the gold standard for diagnosis and prognostication. Because transrectal ultrasound guided prostate biopsy performs poorly, extensive research has been conducted into biopsy techniques that are guided by magnetic resonance imaging, including direct in bore, cognitive fusion and magnetic resonance imaging/ultrasound fusion guided biopsies. METHODS: The PubMed(r) database was searched from inception until January 15, 2014 for criteria pertaining to targeted prostate biopsy. RESULTS: Initial studies of the 3 types of targeted prostate biopsy yielded similar results. Most importantly, targeted biopsy detects a greater amount of clinically significant prostate cancer than does transrectal ultrasound guided biopsy. Magnetic resonance imaging/ultrasound fusion guided biopsy has generated the most interest, as it is an office based procedure that does not require a significant change from the current workflow of transrectal prostate biopsy. These techniques hold great promise in the areas of patient selection for definitive treatment, appropriate screening, active surveillance and focal therapy for prostate cancer. CONCLUSIONS: Targeted prostate biopsy has the potential to significantly improve the way patients are screened, treated and monitored in the setting of prostate cancer. These techniques allow for an individualized approach to each patient, which is a substantial improvement over the current practice of effectively random prostate biopsies. Large, multicenter studies are necessary to determine whether targeted prostate biopsy will become a definitive standard of care. PMID- 28989952 TI - Synthesis and characterization of thermally responsive N-isopropylacrylamide hydrogels copolymerized with novel hydrophobic polyphenolic crosslinkers. AB - Two series of thermosensitive hydrogels were synthesized by copolymerizing N isopropylacrylamide (NIPAAm) with various contents of novel hydrophobic crosslinkers, curcumin multiacrylate (CMA) and quercetin multiacrylate (QMA). The compositions of the resulting hydrogels were characterized using solid state-NMR (ss-NMR), and the temperature dependent swelling behavior and lower critical solution temperature (LCST) were characterized using swelling studies and differential scanning calorimetry (DSC). Increasing the crosslinker content resulted in a significant decrease in the LCST and swelling ratio of hydrogels, which could be attributed to the increased hydrophobicity introduced by CMA or QMA. All of the hydrogels demonstrated temperature responsive swelling with the extent of swelling decreasing with increasing crosslinker content. The lower crosslinker content gels displayed sharper phase transitions, while the high crosslinker content gels had broader phase transitions. PMID- 28989954 TI - Inattentional blindness for a gun during a simulated police vehicle stop. AB - People often fail to notice unexpected objects and events when they are focusing attention on something else. Most studies of this "inattentional blindness" use unexpected objects that are irrelevant to the primary task and to the participant (e.g., gorillas in basketball games or colored shapes in computerized tracking tasks). Although a few studies have examined noticing rates for personally relevant or task-relevant unexpected objects, few have done so in a real-world context with objects that represent a direct threat to the participant. In this study, police academy trainees (n = 100) and experienced police officers (n = 75) engaged in a simulated vehicle traffic stop in which they approached a vehicle to issue a warning or citation for running a stop sign. The driver was either passive and cooperative or agitated and hostile when complying with the officer's instructions. Overall, 58% of the trainees and 33% of the officers failed to notice a gun positioned in full view on the passenger dashboard. The driver's style of interaction had little effect on noticing rates for either group. People can experience inattentional blindness for a potentially dangerous object in a naturalistic real-world context, even when noticing that object would change how they perform their primary task and even when their training focuses on awareness of potential threats. PMID- 28989953 TI - Individual differences in perceptual abilities in medical imaging: the Vanderbilt Chest Radiograph Test. AB - Radiologists make many important decisions when detecting nodules on chest radiographs. While training can result in high levels of performance of this task, there could be individual differences in relevant perceptual abilities that are present pre-training. A pre-requisite to address this question is a valid and reliable measure of such abilities. The present work introduces a new measure, the Vanderbilt Chest Radiograph Test (VCRT), which aims to quantify individual differences in perceptual abilities for radiograph-related decision-making in novices. We validate the relevance of the test to diagnostic imaging by verifying radiologists' superior performance on the test compared to novices'. The final VCRT version produces scores with acceptable internal consistency. Then, we investigate how the VCRT can be used in future research by evaluating how the test relates to extant measures of face and object recognition ability. We find that the VCRT shares a small but significant portion of its variance with a measure of novel object recognition, suggesting that some aspect of VCRT performance is driven by a domain-general visual ability. PMID- 28989955 TI - Optimizing learning in undergraduate psychology students: the impact of advance quizzing, review, and classroom attendance. AB - This study investigates whether introducing simple cognitive interventions that are known to enhance learning in laboratory studies can be transferred to classroom settings. In an introductory psychology class, students were provided with a brief advance quiz on the topic covered in each particular lecture. In case they did not attend class, they still had the opportunity to fill it out at home. The interventions were offered on a voluntary basis and the students were given the opportunity to obtain an extra point towards the final exam by reviewing the key points of each lecture on a regular basis. The results indicate that both advance quizzing and review enhanced the grades on the final examination. Although it is likely that individual differences also contribute to learning outcomes, these effects were specific for the particular course and independent from class attendance. The results indicate that transfer of simple cognitive interventions from laboratory to classroom settings is feasible. They also indicate that these interventions can be effectively implemented into the lectures to boost student learning. PMID- 28989956 TI - Rapidly Biodegrading PLGA-Polyurethane Fibers for Sustained Release of Physicochemically Diverse Drugs. AB - Sustained release of physicochemically diverse drugs from electrospun fibers remains a challenge and precludes the use of fibers in many medical applications. Here, we synthesize a new class of polyurethanes with poly(lactic-co-glycolic acid) (PLGA) moieties that degrade faster than polyurethanes based on polycaprolactone. The new polymers, with varying hard to soft segment ratios and fluorobenzene pendant group content, were electrospun into nanofibers and loaded with four physicochemically diverse small molecule drugs. Polymers were characterized using GPC, XPS, and 19F NMR. The size and morphology of electrospun fibers were visualized using SEM, and drug/polymer compatibility and drug crystallinity were evaluated using DSC. We measured in vitro drug release, polymer degradation and cell-culture cytotoxicity of biodegradation products. We show that these newly synthesized PLGA-based polyurethanes degrade up to 65-80% within 4 weeks and are cytocompatible in vitro. The drug-loaded electrospun fibers were amorphous solid dispersions. We found that increasing the hard to soft segment ratio of the polymer enhances the sustained release of positively charged drugs, whereas increasing the fluorobenzene pendant content caused more rapid release of some drugs. In summary, increasing the hard segment or fluorobenzene pendant content of segmented polyurethanes containing PLGA moieties allows for modulation of physicochemically diverse drug release from electrospun fibers while maintaining a biologically relevant biodegradation rate. PMID- 28989957 TI - Display of DNA on Nanoparticles for Targeting Antigen Presenting Cells. AB - Efficient delivery of antigens is of paramount concern in immunotherapies. We aimed to target antigen presenting cells (APCs) by conjugating CpG oligonucleotides to an E2 protein nanoparticle surface (CpG-PEG-E2). Compared to E2 alone, we observed ~4-fold increase of in vitro APC uptake of both CpG-PEG-E2 and E2 conjugated to non-CpG DNA. Furthermore, compared to E2-alone or E2 functionalized solely with polyethylene glycol (PEG), the CpG-PEG-E2 showed enhanced lymph node retention up to at least 48 hr and 2-fold increase in APC uptake in vivo, parameters which are advantageous for vaccine success. This suggests that enhanced APC uptake of nanoparticles mediated by oligonucleotide display may help overcome delivery barriers in vaccine development. PMID- 28989958 TI - Engineering Xeno-Free Microcarriers with Recombinant Vitronectin, Albumin and UV Irradiation for Human Pluripotent Stem Cell Bioprocessing. AB - The development of platforms for the expansion and directed differentiation of human pluripotent stem cells (hPSCs) in large quantities under xeno-free conditions is a key step toward the realization of envisioned stem cell-based therapies. Microcarrier bioreactors afford great surface-to-volume ratio, scalability and customization with typical densities of 106-107 cells/ml or higher. In this study, a simple and inexpensive method was established for generating microcarriers without animal-derived components. While coating polystyrene beads with vitronectin alone did not support the culture of hPSCs in stirred suspension, the inclusion of recombinant human serum albumin and UV irradiation led to enhanced seeding efficiency and retention while cells grew more than 20-fold per passage for multiple successive passages and without loss of cell pluripotency. Human PSCs expanded on microcarriers were coaxed to tri lineage differentiation demonstrating that this system can be used for the self renewal and specification of hPSCs to therapeutically relevant cell types. Such systems will be critical for the envisioned use of stem cells in regenerative medicine and drug discovery. PMID- 28989959 TI - Moving the Conversation on Climate Change and Inequality to the Local: Socio ecological Vulnerability in Agricultural Tanzania. AB - Climate change is expected to shift seasonality in Tanzania, while smallholder farmers' livelihoods and the economy rely upon the success of rainfed agriculture. However, we should not a priori assume doomsday climate vulnerability scenarios of drought and devastation in the rural global South nor, on the other hand, that farmers will optimally employ local knowledge for effective adaptation. Drawing from qualitative fieldwork in two Tanzanian communities, I question these grand narratives of devastation and local adaptive capacity and introduce an approach that brings inequality to the center. Poorer nations are most vulnerable to climate change, but they are not homogenous and neither are the smallholder farmers living within them. I present evidence on the crucial context-specific dimensions of socio-ecological vulnerability for these smallholder farmers-1) water resources and access to them; 2) agricultural knowledge, including farmers' own knowledge and their interactions with sources like government-run agricultural extension and NGOs; and 3) existing drought coping strategies-and the heterogeneity among farmers across these dimensions. Ultimately, this case demonstrates how climate change can reproduce existing inequalities within nations by drawing upon how farmers currently respond to drought as evidence. I present the difficult and somewhat bleak contexts within which the farmers are coping, but also illustrate the agency that farmers exhibit in response to these conditions and the adaptive capacity they possess. Finally, I call for more sub-national research on climate and inequality by sociologists and draw connections among within-nation inequality, climate change, and agricultural development initiatives. PMID- 28989960 TI - Microstructural control of new intercalation layered titanoniobates with large and reversible d-spacing for easy Na+ ion uptake. AB - Key issues for Na-ion batteries are the development of promising electrode materials with favorable sites for Na+ ion intercalation/deintercalation and an understanding of the reaction mechanisms due to its high activation energy and poor electrochemical reversibility. We first report a layered H0.43Ti0.93Nb1.07O5 as a new anode material. This anode material is engineered to have dominant (200) and (020) planes with both a sufficiently large d-spacing of ~8.3 A and two dimensional ionic channels for easy Na+ ion uptake, which leads to a small volume expansion of ~0.6 A along the c direction upon Na insertion (discharging) and the lowest energy barrier of 0.19 eV in the [020] plane among titanium oxide-based materials ever reported. The material intercalates and deintercalates reversibly 1.7 Na ions (~200 mAh g-1) without a capacity fading in a potential window of 0.01 to 3.0 V versus Na/Na+. Na insertion/deinsertion takes place through a solid solution reaction without a phase separation, which prevents coherent strain or stress in the microstructure during cycling and ensures promising sodium storage properties. These findings demonstrate a great potential of H0.43Ti0.93Nb1.07O5 as the anode, and our strategy can be applied to other layered metal oxides for promising sodium storage properties. PMID- 28989961 TI - Topological bootstrap: Fractionalization from Kondo coupling. AB - Topologically ordered phases of matter can host fractionalized excitations known as "anyons," which obey neither Bose nor Fermi statistics. Despite forming the basis for topological quantum computation, experimental access to these exotic phases has been very limited. We present a new route toward realizing fractionalized topological phases by literally building on unfractionalized phases, which are much more easily realized experimentally. Our approach involves a Kondo lattice model in which a gapped electronic system of noninteracting fermions is coupled to local moments via the exchange interaction. Using general entanglement-based arguments and explicit lattice models, we show that gapped spin liquids can be induced in the spin system, and we demonstrate the power of this "topological bootstrap" by realizing chiral and Z2 spin liquids. This technique enables the realization of many long sought-after fractionalized phases of matter. PMID- 28989962 TI - Surface plasmon polariton laser based on a metallic trench Fabry-Perot resonator. AB - Recent years have witnessed a growing interest in the development of small footprint lasers for potential applications in small-volume sensing and on-chip optical communications. Surface plasmons-electromagnetic modes evanescently confined to metal-dielectric interfaces-offer an effective route to achieving lasing at nanometer-scale dimensions when resonantly amplified in contact with a gain medium. We achieve narrow-linewidth visible-frequency lasing at room temperature by leveraging surface plasmons propagating in an open Fabry-Perot cavity formed by a flat metal surface coated with a subwavelength-thick layer of optically pumped gain medium and orthogonally bound by a pair of flat metal sidewalls. We show how the lasing threshold and linewidth can be lowered by incorporating a low-profile tapered grating on the cavity floor to couple the excitation beam into a pump surface plasmon polariton providing a strong modal overlap with the gain medium. Low-perturbation transmission-configuration sampling of the lasing plasmon mode is achieved via an evanescently coupled recessed nanoslit, opening the way to high-figure of merit refractive index sensing of analytes interacting with the open metallic trench. PMID- 28989964 TI - A highly selective and stable ZnO-ZrO2 solid solution catalyst for CO2 hydrogenation to methanol. AB - Although methanol synthesis via CO hydrogenation has been industrialized, CO2 hydrogenation to methanol still confronts great obstacles of low methanol selectivity and poor stability, particularly for supported metal catalysts under industrial conditions. We report a binary metal oxide, ZnO-ZrO2 solid solution catalyst, which can achieve methanol selectivity of up to 86 to 91% with CO2 single-pass conversion of more than 10% under reaction conditions of 5.0 MPa, 24,000 ml/(g hour), H2/CO2 = 3:1 to 4:1, 320 degrees to 315 degrees C. Experimental and theoretical results indicate that the synergetic effect between Zn and Zr sites results in the excellent performance. The ZnO-ZrO2 solid solution catalyst shows high stability for at least 500 hours on stream and is also resistant to sintering at higher temperatures. Moreover, no deactivation is observed in the presence of 50 ppm SO2 or H2S in the reaction stream. PMID- 28989963 TI - Ultrathin thermoresponsive self-folding 3D graphene. AB - Graphene and other two-dimensional materials have unique physical and chemical properties of broad relevance. It has been suggested that the transformation of these atomically planar materials to three-dimensional (3D) geometries by bending, wrinkling, or folding could significantly alter their properties and lead to novel structures and devices with compact form factors, but strategies to enable this shape change remain limited. We report a benign thermally responsive method to fold and unfold monolayer graphene into predesigned, ordered 3D structures. The methodology involves the surface functionalization of monolayer graphene using ultrathin noncovalently bonded mussel-inspired polydopamine and thermoresponsive poly(N-isopropylacrylamide) brushes. The functionalized graphene is micropatterned and self-folds into ordered 3D structures with reversible deformation under a full control by temperature. The structures are characterized using spectroscopy and microscopy, and self-folding is rationalized using a multiscale molecular dynamics model. Our work demonstrates the potential to design and fabricate ordered 3D graphene structures with predictable shape and dynamics. We highlight applicability by encapsulating live cells and creating nonlinear resistor and creased transistor devices. PMID- 28989965 TI - Field-controlled structures in ferromagnetic cholesteric liquid crystals. AB - One of the advantages of anisotropic soft materials is that their structures and, consequently, their properties can be controlled by moderate external fields. Whereas the control of materials with uniform orientational order is straightforward, manipulation of systems with complex orientational order is challenging. We show that a variety of structures of an interesting liquid material, which combine chiral orientational order with ferromagnetic one, can be controlled by a combination of small magnetic and electric fields. In the suspensions of magnetic nanoplatelets in chiral nematic liquid crystals, the platelet's magnetic moments orient along the orientation of the liquid crystal and, consequently, the material exhibits linear response to small magnetic fields. In the absence of external fields, orientations of the liquid crystal and magnetization have wound structure, which can be either homogeneously helical, disordered, or ordered in complex patterns, depending on the boundary condition at the surfaces and the history of the sample. We demonstrate that by using different combinations of small magnetic and electric fields, it is possible to control reversibly the formation of the structures in a layer of the material. In such a way, different periodic structures can be explored and some of them may be suitable for photonic applications. The material is also a convenient model system to study chiral magnetic structures, because it is a unique liquid analog of a solid helimagnet. PMID- 28989966 TI - Ligand effects in catalysis by atomically precise gold nanoclusters. AB - Atomically precise gold nanoclusters are ideal model catalysts with well-defined compositions and tunable structures. Determination of the ligand effect on catalysis requires the use of gold nanoclusters with protecting ligands as the only variable. Two isostructural Au38 nanoclusters, [Au38(L)20(Ph3P)4]2+ (L = alkynyl or thiolate), have been synthesized by a direct reduction method, and they have an unprecedented face-centered cubic (fcc)-type Au34 kernel surrounded by 4 AuL2 staple motifs, 4 Ph3P, and 12 bridging L ligands. The Au34 kernel can be derived from the fusion of two fcc-type Au20 via sharing a Au6 face. Catalytic performance was studied with these two nanoclusters supported on TiO2 (1/TiO2 and 2/TiO2) as catalysts. The alkynyl-protected Au38 are very active (>97%) in the semihydrogenation of alkynes (including terminal and internal ones) to alkenes, whereas the thiolated Au38 showed a very low conversion (<2%). This fact suggests that the protecting ligands play an important role in H2 activation. This work presents a clear demonstration that catalytic performance of gold nanoclusters can be modulated by the controlled construction of ligand spheres. PMID- 28989967 TI - Tailoring tricolor structure of magnetic topological insulator for robust axion insulator. AB - Exploration of novel electromagnetic phenomena is a subject of great interest in topological quantum materials. One of the unprecedented effects to be experimentally verified is the topological magnetoelectric (TME) effect originating from an unusual coupling of electric and magnetic fields in materials. A magnetic heterostructure of topological insulator (TI) hosts such exotic magnetoelectric coupling and can be expected to realize the TME effect as an axion insulator. We designed a magnetic TI with a tricolor structure where a nonmagnetic layer of (Bi, Sb)2Te3 is sandwiched by a soft ferromagnetic Cr-doped (Bi, Sb)2Te3 and a hard ferromagnetic V-doped (Bi, Sb)2Te3. Accompanied by the quantum anomalous Hall (QAH) effect, we observe zero Hall conductivity plateaus, which are a hallmark of the axion insulator state, in a wide range of magnetic fields between the coercive fields of Cr- and V-doped layers. The resistance of the axion insulator state reaches as high as 109 ohms, leading to a gigantic magnetoresistance ratio exceeding 10,000,000% upon the transition from the QAH state. The tricolor structure of the TI may not only be an ideal arena for the topologically distinct phenomena but can also provide magnetoresistive applications for advancing dissipation-less topological electronics. PMID- 28989968 TI - Unexpected high robustness of electrochemical cross-coupling for a broad range of current density. AB - Electro-organic synthesis is a powerful technique for the sustainable preparation of compounds. However, many electrosynthetic reactions require complex equipment, are limited to a very narrow current density range, or have very long reaction times; some also involve nonselective transformations and bad scalability. The robust and selective synthesis of nonsymmetric biphenols and partially protected derivatives is established by anodic C-C cross-coupling. The setup is simple, involving constant current conditions and undivided cells. Its key is a unique electrolyte system based on fluorous alcohols and mixtures, particularly 1,1,1,3,3,3-hexafluoroisopropanol. This allows variations of the current density of more than two orders of magnitude without decreasing selectivity or product yield. This exceptional effect is unknown for electro-organic synthesis of products that have similar oxidation potentials as the starting materials. It potentially paves the way for industrial electrolyzers with variable current consumption, which could enable the flexible use of energy surplus in the electricity supply. PMID- 28989969 TI - Structural Characterization of Clostridium sordellii Spores of Diverse Human, Animal, and Environmental Origin and Comparison to Clostridium difficile Spores. AB - Clostridium sordellii is an often-lethal bacterium causing human and animal disease. Crucial to the infectious cycle of C. sordellii is its ability to produce spores, which can germinate into toxin-producing vegetative bacteria under favorable conditions. However, structural details of the C. sordellii spore are lacking. Here, we used a range of electron microscopy techniques together with superresolution optical microscopy to characterize the C. sordellii spore morphology with an emphasis on the exosporium. The C. sordellii spore is made up of multiple layers with the exosporium presenting as a smooth balloon-like structure that is open at the spore poles. Focusing on the outer spore layers, we compared the morphologies of C. sordellii spores derived from different strains and determined that there is some variation between the spores, most notably with spores of some strains having tubular appendages. Since Clostridium difficile is a close relative of C. sordellii, their spores were compared by electron microscopy and their exosporia were found to be distinctly different from each other. This study therefore provides new structural details of the C. sordellii spore and offers insights into the physical structure of the exosporium across clostridial species. IMPORTANCEClostridium sordellii is a significant pathogen with mortality rates approaching 100%. It is the bacterial spore that is critical in initiating infection and disease. An understanding of spore structures as well as spore morphology across a range of strains may lead to a better understanding of C. sordellii infection and disease. However, the structural characteristics of the C. sordellii spores are limited. In this work, we have addressed this lack of detail and characterized the C. sordellii spore morphology. The use of traditional and advanced microscopy techniques has provided detailed new observations of C. sordellii spore structural features, which serve as a reference point for structural studies of spores from other bacterial species. PMID- 28989970 TI - Virioplankton Assemblage Structure in the Lower River and Ocean Continuum of the Amazon. AB - The Amazon River watershed and its associated plume comprise a vast continental and oceanic area. The microbial activities along this continuum contribute substantially to global carbon and nutrient cycling, and yet there is a dearth of information on the diversity, abundance, and possible roles of viruses in this globally important river. The aim of this study was to elucidate the diversity and structure of virus assemblages of the Amazon River-ocean continuum. Environmental viral DNA sequences were obtained for 12 locations along the river's lower reach (n = 5) and plume (n = 7). Sequence assembly yielded 29,358 scaffolds, encoding 82,546 viral proteins, with 15 new complete viral genomes. Despite the spatial connectivity mediated by the river, virome analyses and physical-chemical water parameters clearly distinguished river and plume ecosystems. Bacteriophages were ubiquitous in the continuum and were more abundant in the transition region. Eukaryotic viruses occurred mostly in the river, while the plume had more viruses of autotrophic organisms (Prochlorococcus, Synechococcus) and heterotrophic bacteria (Pelagibacter). The viral families Microviridae and Myoviridae were the most abundant and occurred throughout the continuum. The major functions of the genes in the continuum involved viral structures and life cycles, and viruses from plume locations and Tapajos River showed the highest levels of functional diversity. The distribution patterns of the viral assemblages were defined not only by the occurrence of possible hosts but also by water physical and chemical parameters, especially salinity. The findings presented here help to improve understanding of the possible roles of viruses in the organic matter cycle along the river-ocean continuum. IMPORTANCE The Amazon River forms a vast plume in the Atlantic Ocean that can extend for more than 1,000 km. Microbial communities promote a globally relevant carbon sink system in the plume. Despite the importance of viruses for the global carbon cycle, the diversity and the possible roles of viruses in the Amazon are poorly understood. The present work assesses, for the first time, the abundance and diversity of viruses simultaneously in the river and ocean in order to elucidate their possible roles. DNA sequence assembly yielded 29,358 scaffolds, encoding 82,546 viral proteins, with 15 new complete viral genomes from the 12 river and ocean locations. Viral diversity was clearly distinguished by river and ocean. Bacteriophages were the most abundant and occurred throughout the continuum. Viruses that infect eukaryotes were more abundant in the river, whereas phages appeared to have strong control over the host prokaryotic populations in the plume. PMID- 28989971 TI - Target Abundance-Based Fitness Screening (TAFiS) Facilitates Rapid Identification of Target-Specific and Physiologically Active Chemical Probes. AB - Traditional approaches to drug discovery are frustratingly inefficient and have several key limitations that severely constrain our capacity to rapidly identify and develop novel experimental therapeutics. To address this, we have devised a second-generation target-based whole-cell screening assay based on the principles of competitive fitness, which can rapidly identify target-specific and physiologically active compounds. Briefly, strains expressing high, intermediate, and low levels of a preselected target protein are constructed, tagged with spectrally distinct fluorescent proteins (FPs), and pooled. The pooled strains are then grown in the presence of various small molecules, and the relative growth of each strain within the mixed culture is compared by measuring the intensity of the corresponding FP tags. Chemical-induced population shifts indicate that the bioactivity of a small molecule is dependent upon the target protein's abundance and thus establish a specific functional interaction. Here, we describe the molecular tools required to apply this technique in the prevalent human fungal pathogen Candida albicans and validate the approach using two well characterized drug targets-lanosterol demethylase and dihydrofolate reductase. However, our approach, which we have termed target abundance-based fitness screening (TAFiS), should be applicable to a wide array of molecular targets and in essentially any genetically tractable microbe. IMPORTANCE Conventional drug screening typically employs either target-based or cell-based approaches. The first group relies on biochemical assays to detect modulators of a purified target. However, hits frequently lack drug-like characteristics such as membrane permeability and target specificity. Cell-based screens identify compounds that induce a desired phenotype, but the target is unknown, which severely restricts further development and optimization. To address these issues, we have developed a second-generation target-based whole-cell screening approach that incorporates the principles of both chemical genetics and competitive fitness, which enables the identification of target-specific and physiologically active compounds from a single screen. We have chosen to validate this approach using the important human fungal pathogen Candida albicans with the intention of pursuing novel antifungal targets. However, this approach is broadly applicable and is expected to dramatically reduce the time and resources required to progress from screening hit to lead compound. PMID- 28989972 TI - A New Take on an Old Remedy: Generating Antibodies against Multidrug-Resistant Gram-Negative Bacteria in a Postantibiotic World. AB - With the problem of multidrug-resistant Gram-negative pathogens becoming increasingly dire, new strategies are needed to protect and treat infected patients. Though abandoned in the past, monoclonal antibody therapy against Gram negative bacteria remains a potential solution and has potential advantages over the broad-spectrum antibiotics they were once replaced by. This Perspective reviews the prospect of utilizing monoclonal antibody therapy against these pathogens, as well as the challenges of doing so and the current therapy targets under investigation. PMID- 28989974 TI - Arresting Dentine Caries with Different Concentration and Periodicity of Silver Diamine Fluoride. AB - Different regimens of silver diamine fluoride (SDF) have been used to manage early childhood caries. So far, there is limited information regarding the concentrations and frequency of applications for effective caries control in primary teeth. This study aimed to compare the efficacy of 2 commercially available SDF solutions at preprepared concentrations of 38% and 12% when applied annually or biannually over 18 mo in arresting dentine caries in primary teeth. This randomized double-blinded clinical trial recruited kindergarten children aged 3 to 4 y who had at least 1 tooth with dentine caries. The children were randomly allocated to receive 4 treatment protocols: group 1, annual application of 12% SDF; group 2, biannual application of 12% SDF; group 3, annual application of 38% SDF; and group 4, biannual application of 38% SDF. Clinical examinations at 6-mo intervals were conducted to assess whether active carious lesions became arrested. Information on the children's background and oral hygiene habits was collected through a parental questionnaire at baseline and follow-up examinations. A total of 888 children with 4,220 dentine carious tooth surfaces received treatment at baseline. After 18 mo, 831 children (94%) were examined. The caries arrest rates were 50%, 55%, 64%, and 74% for groups 1, 2, 3, and 4, respectively (P < 0.001). Lesions treated with SDF biannual application had a higher chance of becoming arrested compared with those receiving SDF annual application (odds ratio, 1.33; 95% confidence interval, 1.04-1.71; P = 0.025). The interaction between concentration and lesion site was statistically significant (P < 0.001). Compared with 12% SDF, the use of 38% SDF increased a chance of becoming arrested (P < 0.05), except lesions on occlusal surfaces. Based on the 18-mo results, SDF is more effective in arresting dentin caries in the primary teeth of preschool children at 38% concentration than 12% concentration and when applied biannually rather than annually. Knowledge Transfer Statement: The results of this study can be used by clinicians and dental public health professionals when deciding which concentrations and frequency of application of silver diamine fluoride solution should be adopted for arresting dentine caries. With consideration of caries arrest treatment with silver diamine fluoride, which is painless, simple, and low cost, this information could lead to more appropriate therapeutic decisions for caries control in young children or those who lack access to affordable conventional dental care. PMID- 28989973 TI - Cloning, Assembly, and Modification of the Primary Human Cytomegalovirus Isolate Toledo by Yeast-Based Transformation-Associated Recombination. AB - Genetic engineering of cytomegalovirus (CMV) currently relies on generating a bacterial artificial chromosome (BAC) by introducing a bacterial origin of replication into the viral genome using in vivo recombination in virally infected tissue culture cells. However, this process is inefficient, results in adaptive mutations, and involves deletion of viral genes to avoid oversized genomes when inserting the BAC cassette. Moreover, BAC technology does not permit the simultaneous manipulation of multiple genome loci and cannot be used to construct synthetic genomes. To overcome these limitations, we adapted synthetic biology tools to clone CMV genomes in Saccharomyces cerevisiae. Using an early passage of the human CMV isolate Toledo, we first applied transformation-associated recombination (TAR) to clone 16 overlapping fragments covering the entire Toledo genome in Saccharomyces cerevisiae. Then, we assembled these fragments by TAR in a stepwise process until the entire genome was reconstituted in yeast. Since next generation sequence analysis revealed that the low-passage-number isolate represented a mixture of parental and fibroblast-adapted genomes, we selectively modified individual DNA fragments of fibroblast-adapted Toledo (Toledo-F) and again used TAR assembly to recreate parental Toledo (Toledo-P). Linear, full length HCMV genomes were transfected into human fibroblasts to recover virus. Unlike Toledo-F, Toledo-P displayed characteristics of primary isolates, including broad cellular tropism in vitro and the ability to establish latency and reactivation in humanized mice. Our novel strategy thus enables de novo cloning of CMV genomes, more-efficient genome-wide engineering, and the generation of viral genomes that are partially or completely derived from synthetic DNA. IMPORTANCE The genomes of large DNA viruses, such as human cytomegalovirus (HCMV), are difficult to manipulate using current genetic tools, and at this time, it is not possible to obtain, molecular clones of CMV without extensive tissue culture. To overcome these limitations, we used synthetic biology tools to capture genomic fragments from viral DNA and assemble full length genomes in yeast. Using an early passage of the HCMV isolate Toledo containing a mixture of wild-type and tissue culture-adapted virus. we directly cloned the majority sequence and recreated the minority sequence by simultaneous modification of multiple genomic regions. Thus, our novel approach provides a paradigm to not only efficiently engineer HCMV and other large DNA viruses on a genome-wide scale but also facilitates the cloning and genetic manipulation of primary isolates and provides a pathway to generating entirely synthetic genomes. PMID- 28989976 TI - Hematopoietic Stem Cell-derived Adipocytes Promote Tumor Growth and Cancer Cell Migration. AB - Adipocytes, apart from their critical role as the energy storage depots, contribute to the composition of the tumor microenvironment. Our previous studies based on a single hematopoietic stem cell (HSC) transplantation model, have revealed a novel source of adipocytes from HSCs via monocyte/macrophage progenitors. Herein, we extend these studies to examine the role of HSC-derived adipocytes (HSC-Ad) in tumor progression. When cultured under adipogenic conditions, bone marrow-derived monocytic progenitors differentiated into adipocytes that accumulated oil droplets containing triglyceride. The adipokine array and ELISAs confirmed secretion of multiple adipokines by HSC-Ad. These adipocytes underwent further development in vivo when injected subcutaneously into C57Bl/6 mice. When co-injected with melanoma B16F1 cells or breast cancer E0771 cells into syngeneic C57Bl/6 mice, HSC-Ad not only accelerated both melanoma and breast tumor growth, but also enhanced vascularization in both tumors. Conditioned media from HSC-Ad supported B16F1 and E0771 cell proliferation and enhanced cell migration in vitro. Among the HSC-Ad secreted adipokines, insulin-like growth factor 1 (IGF-1) played an important role in E0771 cell proliferation. Hepatocyte growth factor (HGF) was indispensable for B16F1 cell migration, whereas HGF and platelet-derived growth factor BB (PDGF-BB) collectively contributed to E0771 cell migration. Expression levels of receptors for IGF-1, HGF, and PDGF-BB correlated with their differential roles in B16F1 and E0771 cell proliferation and migration. Our data suggest that HSC-Ad differentially regulate tumor behavior through distinct mechanisms. PMID- 28989975 TI - Peptide-Based Supramolecular Hydrogels for Delivery of Biologics. AB - The demand for therapeutic biologics has rapidly grown over recent decades, creating a dramatic shift in the pharmaceutical industry from small molecule drugs to biological macromolecular therapeutics. As a result of their large size and innate instability, the systemic, topical, and local delivery of biologic drugs remains a highly challenging task. Although there exist many types of delivery vehicles, peptides and peptide conjugates have received continuously increasing interest as molecular blocks to create a great diversity of supramolecular nanostructures and hydrogels for the effective delivery of biologics, due to their inherent biocompatibility, tunable biodegradability, and responsiveness to various biological stimuli. In this context, we discuss the design principles of supramolecular hydrogels using small molecule peptides and peptide conjugates as molecular building units, and review the recent effort in using these materials for protein delivery and gene delivery. PMID- 28989977 TI - Fear reduction without fear through reinforcement of neural activity that bypasses conscious exposure. PMID- 28989978 TI - The therapeutic potential of resveratrol: a review of clinical trials. AB - Resveratrol is a nutraceutical with several therapeutic effects. It has been shown to mimic effects of caloric restriction, exert anti-inflammatory and anti oxidative effects, and affect the initiation and progression of many diseases through several mechanisms. While there is a wealth of in vitro and in vivo evidence that resveratrol could be a promising therapeutic agent, clinical trials must confirm its potential. In this work, we reviewed the current clinical data available regarding the pharmacological action of resveratrol. Most of the clinical trials of resveratrol have focused on cancer, neurological disorders, cardiovascular diseases, diabetes, non-alcoholic fatty liver disease (NAFLD), and obesity. We found that for neurological disorders, cardiovascular diseases, and diabetes, the current clinical trials show that resveratrol was well tolerated and beneficially influenced disease biomarkers. However resveratrol had ambiguous and sometimes even detrimental effects in certain types of cancers and in NAFLD. In most of the clinical trials, the major obstacle presented was resveratrol's poor bioavailability. Thus, this work provides useful considerations for the planning and design of future pre-clinical and clinical research on resveratrol. PMID- 28989981 TI - Synthetic ALSPAC longitudinal datasets for the Big Data VR project. AB - Three synthetic datasets - of observation size 15,000, 155,000 and 1,555,000 participants, respectively - were created by simulating eleven cardiac and anthropometric variables from nine collection ages of the ALSAPC birth cohort study. The synthetic datasets retain similar data properties to the ALSPAC study data they are simulated from (co-variance matrices, as well as the mean and variance values of the variables) without including the original data itself or disclosing participant information. In this instance, the three synthetic datasets have been utilised in an academia-industry collaboration to build a prototype virtual reality data analysis software, but they could have a broader use in method and software development projects where sensitive data cannot be freely shared. PMID- 28989979 TI - Haplotype-based association analysis of general cognitive ability in Generation Scotland, the English Longitudinal Study of Ageing, and UK Biobank. AB - BACKGROUND: Cognitive ability is a heritable trait with a polygenic architecture, for which several associated variants have been identified using genotype-based and candidate gene approaches. Haplotype-based analyses are a complementary technique that take phased genotype data into account, and potentially provide greater statistical power to detect lower frequency variants. METHODS: In the present analysis, three cohort studies (n total = 48,002) were utilised: Generation Scotland: Scottish Family Health Study (GS:SFHS), the English Longitudinal Study of Ageing (ELSA), and the UK Biobank. A genome-wide haplotype based meta-analysis of cognitive ability was performed, as well as a targeted meta-analysis of several gene coding regions. RESULTS: None of the assessed haplotypes provided evidence of a statistically significant association with cognitive ability in either the individual cohorts or the meta-analysis. Within the meta-analysis, the haplotype with the lowest observed P-value overlapped with the D-amino acid oxidase activator ( DAOA) gene coding region. This coding region has previously been associated with bipolar disorder, schizophrenia and Alzheimer's disease, which have all been shown to impact upon cognitive ability. Another potentially interesting region highlighted within the current genome-wide association analysis (GS:SFHS: P = 4.09 x 10 -7), was the butyrylcholinesterase ( BCHE) gene coding region. The protein encoded by BCHE has been shown to influence the progression of Alzheimer's disease and its role in cognitive ability merits further investigation. CONCLUSIONS: Although no evidence was found for any haplotypes with a statistically significant association with cognitive ability, our results did provide further evidence that the genetic variants contributing to the variance of cognitive ability are likely to be of small effect. PMID- 28989982 TI - An exploration into caring for a stroke-survivor in Lima, Peru: Emotional impact, stress factors, coping mechanisms and unmet needs of informal caregivers. AB - INTRODUCTION: Understanding local complexities and challenges of stroke-related caregiving are essential to develop appropriate interventions. Our study aimed to characterize the impact of post-stroke care among caregivers in a setting of transitioning economy. MATERIALS AND METHODS: Qualitative study based on in-depth interviews with primary caregivers of stroke survivors in Lima, Peru. Transcribed data was organized into the emotional impact of caregiving, main stress factors and coping mechanisms to deal with the caregiving role, as well as the unmet needs of caregivers. RESULTS: We interviewed twelve caregivers, mean age 52.5 years, 8/12 were females, who were either the spouse or child of the stroke survivor. Stroke patients had a median age of 70 years, range 53-85 years. All participants reported having experienced emotional stress and depressive symptoms as a result of caregiving. Although most had family support, reduced social activities and added unanticipated financial burdens increased caregiver's stress. None of the caregivers had received training in post-stroke care tasks after the patient's discharge and only a few had received some psychological support, yet almost all expressed the need to see a professional to improve their mental health. Keeping a positive attitude towards their relative's physical post stroke condition was a key coping mechanism. CONCLUSIONS: In the absence of structured institutional responses, family members endure with the provision of care for stroke survivors, a task escorted by major emotional, financial, and social strains. This burden could be prevented or curtailed if caregivers were to be targeted by interventions providing psychological and financial support, together with basic training on post-stroke care. PMID- 28989980 TI - Bone mineral density and risk of type 2 diabetes and coronary heart disease: A Mendelian randomization study. AB - Background: Observational studies have demonstrated that increased bone mineral density is associated with a higher risk of type 2 diabetes (T2D), but the relationship with risk of coronary heart disease (CHD) is less clear. Moreover, substantial uncertainty remains about the causal relevance of increased bone mineral density for T2D and CHD, which can be assessed by Mendelian randomisation studies. Methods: We identified 235 independent single nucleotide polymorphisms (SNPs) associated at p<5*10 -8 with estimated heel bone mineral density (eBMD) in 116,501 individuals from the UK Biobank study, accounting for 13.9% of eBMD variance. For each eBMD-associated SNP, we extracted effect estimates from the largest available GWAS studies for T2D (DIAGRAM: n=26,676 T2D cases and 132,532 controls) and CHD (CARDIoGRAMplusC4D: n=60,801 CHD cases and 123,504 controls). A two-sample design using several Mendelian randomization approaches was used to investigate the causal relevance of eBMD for risk of T2D and CHD. In addition, we explored the relationship of eBMD, instrumented by the 235 SNPs, on 12 cardiovascular and metabolic risk factors. Finally, we conducted Mendelian randomization analysis in the reverse direction to investigate reverse causality. Results: Each one standard deviation increase in genetically instrumented eBMD (equivalent to 0.14 g/cm 2) was associated with an 8% higher risk of T2D (odds ratio [OR] 1.08; 95% confidence interval [CI]: 1.02 to 1.14; p=0.012) and 5% higher risk of CHD (OR 1.05; 95%CI: 1.00 to 1.10; p=0.034). Consistent results were obtained in sensitivity analyses using several different Mendelian randomization approaches. Equivalent increases in eBMD were also associated with lower plasma levels of HDL-cholesterol and increased insulin resistance. Mendelian randomization in the reverse direction using 94 T2D SNPs or 52 CHD SNPs showed no evidence of reverse causality with eBMD. Conclusions: These findings suggest a causal relationship between elevated bone mineral density with risks of both T2D and CHD. PMID- 28989983 TI - Prevalence of historical and replacement brominated flame retardant chemicals in New York City homes. AB - BACKGROUND: Until their phase-out between 2005 and 2013, polybrominated diphenyl ethers (PBDEs) were added to household products including furniture, rugs, and electronics to meet flammability standards. Replacement brominated flame retardant (BFR) chemicals, including 2-ethylhexyl-2,3,4,5 tetrabromobenzoate (TBB) and bis(2-ethylhexyl) 2,3,4,5-tetrabromophthalate (TBPH), which are components of the Firemaster 550(r) commercial mixture, are now being used to meet some flammability standards in furniture. The objective of this analysis was to evaluate the extent to which mothers and their children living in New York City are exposed to PBDEs, TBB, and TBPH. METHODS: We measured PBDEs, TBB, and TBPH using gas chromatography mass spectrometry in dust (n = 25) and handwipe (n = 11) samples collected between 2012 and 2013 from mothers and children living in New York City. We defined dust as enriched if the proportional distribution for a given BFR exceeded two-thirds of the total BFR content. RESULTS: We detected PBDEs and TBPH in 100% of dust and handwipe samples and TBB in 100% of dust samples and 95% of handwipe samples. Dust from approximately two-thirds of households was enriched for either PBDEs (n = 9) or for TBB + TBPH (n = 8). Overall, the median house dust concentration of TBB + TBPH (1318 ng/g dust) was higher than that of SigmaPentaBDE (802 ng/g dust) and BDE-209 (1171 ng/g dust). Children generally had higher BFR handwipe concentrations compared to mothers (SigmaPentaBDE: 73%, BDE-209: 64%, TBB + TBPH: 55%) and within households, BFR concentrations from paired maternal-child handwipes were highly correlated. Among mothers, we found a significant positive relation between house dust and handwipe BDE-209 and TBB + TBPH concentrations. CONCLUSION: PBDEs, TBB and TBPH are ubiquitous in house dust and handwipes in a sample of mother-child pairs residing in New York City. PMID- 28989984 TI - Hippocampal volume changes following electroconvulsive therapy: a systematic review and meta-analysis. AB - INTRODUCTION: Reduced hippocampal volume is one of the most consistent morphological findings in Major Depressive Disorder (MDD). Electroconvulsive therapy (ECT) is the most effective therapy for MDD, yet its mechanism of action remains poorly understood. Animal models show that ECT induces several neuroplastic processes, which lead to hippocampal volume increases. We conducted a meta-analysis of ECT studies in humans to investigate its effects on hippocampal volume. METHODS: PubMed was searched for studies examining hippocampal volume before and after ECT. A random-effects model was used for meta analysis with standardized mean difference (SMD) of the change in hippocampal volume before and after ECT as the primary outcome. Nine studies involving 174 participants were included. RESULTS: Total hippocampal volumes increased significantly following ECT compared to pre-treatment values (SMD=1.10; 95% CI 0.80-1.39; z=7.34; p<0.001; k=9). Both right (SMD=1.01; 95% CI 0.72-1.30; z=6.76; p<0.001; k=7) and left (SMD=0.87; 95% CI 0.51-1.23; z=4.69; p<0.001; k=7) hippocampal volumes were also similarly increased significantly following ECT. We demonstrated no correlation between improvement in depression symptoms with ECT and change in total hippocampal volume (beta=-1.28, 95% CI -4.51-1.95, z=-0.78, p=0.44). CONCLUSION: We demonstrate fairly consistent increases in hippocampal volume bilaterally following ECT treatment. The relationship among these volumetric changes and clinical improvement and cognitive side effects of ECT should be explored by larger, multisite studies with harmonized imaging methods. PMID- 28989985 TI - Cardiac Lymphatic Vessels, Transport, and Healing of the Infarcted Heart. AB - The lymphatic vasculature plays a key role throughout the body in regulating tissue fluid homeostasis, lipid transport, and immune surveillance. Whereas it has been appreciated that the heart relies on lymphatic vessels to maintain fluid balance and that such balance must be tightly maintained to allow for normal cardiac output, it has only recently come to light that the lymphatic vasculature might serve as a therapeutic target to promote optimal healing following myocardial ischemia and infarction. We review the subject of cardiac lymphatic vessels herein and highlight studies that imply targeting of lymphatic vessel development or transport may serve as a promising avenue for future clinical application in the context of ischemic injury. PMID- 28989986 TI - Data Resources for Human Functional Genomics. PMID- 28989987 TI - Towards a better cancer precision medicine: systems biology meets immunotherapy. AB - Systems biology approaches that embrace the complexity of cancer are starting to gain traction in the development of new anticancer therapeutic strategies. In this review we describe how genomic analyses are helping improve our understanding of response to immunotherapy, a front-runner in cancer treatment. We argue that systems-level approaches are needed to help understand the concerted impact of tumor-specific and immune-specific molecular features on clinical outcomes, predict responders and unravel the complexity of tumor ecosystems. This integrated approach will propel immunotherapy into the exciting world of precision medicine. PMID- 28989988 TI - A Risk-based Model for Predicting the Impact of using Condoms on the Spread of Sexually Transmitted Infections. AB - We create and analyze a mathematical model to estimate the impact of condom-use and sexual behavior on the prevalence and spread of Sexually Transmitted Infections (STIs). STIs remain a significant public health challenge globally with a high burden of some Sexually Transmitted Diseases (STDs) in both developed and undeveloped countries. Although condom-use is known to reduce the transmission of STIs, there are a few quantitated population-based studies on the protective role of condom-use in reducing the incidence of STIs. The number of concurrent partners is correlated with their risk of being infectious by a STI such as chlamydia, gonorrhea, or syphilis. We define a Susceptible-Infectious Susceptible (SIS) model that distributes the population by the number of concurrent partners. The model captures the multi-level heterogeneous mixing through a combination of biased (preferential) and random mixing between individuals with different risks, and accounts for differences in condom-use in the low- and high-risk populations. We use sensitivity analysis to assess the relative impact of high-risk people using condom as a prophylactic to reduce their chance of being infectious, or infecting others. The model predicts the STI prevalence as a function of the number of partners that a person has, and quantifies how this distribution changes as a function of condom-use. Our results show that when the mixing is random, then increasing the condom-use in the high risk population is more effective in reducing the prevalence than when many of the partners of high-risk people have high risk. The model quantified how the risk of being infected increases for people who have more partners, and and the need for high-risk people to consistently use condoms to reduce their risk of infection. PMID- 28989989 TI - Immunotoxicology: A brief history, current status and strategies for future immunotoxicity assessment. PMID- 28989990 TI - Molecular Breast Imaging using Synthetic Projections from High-Purity Germanium Detectors: A Simulation Study. AB - High-Purity Germanium (HPGe) gamma cameras are an emerging technology for Molecular Breast Imaging (MBI) due to their 2D lateral spatial resolution, depth of-interaction (DOI) estimation, and superb energy resolution. In this simulation study, we investigate the potential imaging performance of an opposing view dual head HPGe breast imaging system using a synthetic-projection technique, which utilizes DOI data with varying degrees of overlap in an iterative OSEM reconstruction algorithm to create 3D images from which new 2D projections are then created. The radiation transport simulator Monte Carlo N-Particle was employed to generate projections from 10-mm thick HPGe detectors using tungsten parallel-hole collimators with short and wide holes. Simulations modeling 140-keV emissions from various contrast-detail and breast-torso phantoms were conducted. Synthetic projections were generated along with conjugate-counting images from collected HPGe projections. Tumor contrast, SNR, and hot-spot detection measurements were used to compare images. Results show that the synthetic projections could resolve more low-contrast tumors compared to single-camera projections and conjugate-counting methods. MBI simulations also showed increased contrast and SNR in synthetic projections compared to individual projections. In conclusion, the HPGe imaging system employing a synthetic-projection technique may offer advantages over individual dual-camera projections or conjugate counting methods in terms of contrast, SNR, and tumor detectability. PMID- 28989991 TI - Region Specific Effects of Aging and the Nurr1-Null Heterozygous Genotype on Dopamine Neurotransmission. AB - The transcription factor Nurr1 is essential for dopamine neuron differentiation and is important in maintaining dopamine synthesis and neurotransmission in the adult. Reduced Nurr1 function, due to the Nurr1-null heterozygous genotype (+/-), impacts dopamine neuron function in a region specific manner resulting in a decrease in dopamine synthesis in the dorsal and ventral striatum and a decrease in tissue dopamine levels in the ventral striatum. Additionally, maintenance of tissue dopamine levels in the dorsal striatum and survival of nigrostriatal dopamine neurons with aging (>15 months) or after various toxicant treatments are impaired. To further investigate the effects of aging and the Nurr1-null heterozygous genotype, we measured regional tissue dopamine levels, dopamine neuron numbers, body weight, open field activity and rota-rod performance in young (3-5 months) and aged (15-17 months) wild-type +/+ and +/- mice. Behavioral tests revealed no significant differences in rota-rod performance or basal open field activity as a result of aging or genotype. The +/- mice did show a significant increase in open field activity after 3 min of restraint stress. No differences in tissue dopamine levels were found in the dorsal striatum. However, there were significant reductions in tissue dopamine levels in the ventral striatum, which was separated into the nucleus accumbens core and shell, in the aged +/- mice. These data indicate that the mesoaccumbens system is more susceptible to the combination of aging and the +/- genotype than the nigrostriatal system. Additionally, the effects of aging and the +/- genotype may be dependent on genetic background or housing conditions. As Nurr1 mutations have been implicated in a number of diseases associated with dopamine neurotransmission, further data is needed to understand why and how Nurr1 can have differential functions across different dopamine neuron populations in aging. PMID- 28989994 TI - Arteriovenous Malformation in a Youth with Atypical Autism Symptoms. AB - Cerebral arteriovenous malformations (AVMs) present a challenge to diagnose in children with developmental disability, because of the overlap in behavioral symptoms and neurologic manifestations. They have been very rarely reported in conjunction with autism spectrum disorder. This case involves a 13 year old male with a history of autism spectrum disorder and significant behavioral issues diagnosed with a thalamic AVM following lateralizing neurologic symptoms. Despite radiosurgical treatment, hemorrhage followed consequently causing extensive neurologic injury and death. This case emphasizes the need for close follow up and coordination within a medical home for children with developmental disabilities. A multidisciplinary team approach is ideal to allow detection of subtle neurologic changes over time that may be masked as behavioral difficulties. PMID- 28989995 TI - COLLAGE 360: A Model of Person-Centered Care To Promote Health Among Older Adults. AB - Health care leaders and providers have introduced the assumption the typical elder, even in the presence of complex, chronic disease and prevailing illness, is capable of assuming greater personal responsibility for their health care, with a shift from provider-centered to a person-centered model of care. For older adults who often and repeatedly face challenges managing and maintaining their health status, guidance and support is needed. In this study, COLLAGE 360, a comprehensive assessment system and wellness coaching program that focuses on prevention and wellness, care coordination and self-management of health care was implemented in one continuing care retirement community. Following completion of two assessment tools via directed conversation with a wellness coach, older adults developed an individualized vitality plan that outlined life goals, supporting goals and action plans for goal achievement. Results from this program suggest engagement in the assessment and wellness coaching process via the COLLAGE 360 program translated into sample older adults sensing that they live in a more supportive environment when compared with elders not receiving any wellness coaching. In addition, the older adults had positive effects in the areas of mood, loneliness, social interaction, health status, and life satisfaction. Strategies to improve health and well being need an extended focus beyond the older adult's medical conditions and consider psychological, spiritual and social needs with personal preferences being paramount. These issues are foundational to a person-centered, health promotion approach needed among this population. PMID- 28989996 TI - Clinicopathological features and post-resection outcomes of biliary cystadenoma and cystadenocarcinoma of the liver. AB - BACKGROUNDS/AIMS: Biliary cystadenoma (BCA) and biliary cystadenocarcinoma (BCAC) account for 5%-10% of liver cystic diseases. In this study, we analysed the clinical presentation and surgical management of patients with BCA and BCAC. METHODS: We retrospectively analysed the medical records of 23 BCA and 7 BCAC cases diagnosed between January 2007 and December 2013. RESULTS: There was a statistically significant difference in age (p=0.044) and sex (p=0.048) between BCA and BCAC groups. In the BCA group, 17 patients showed no symptoms (74%), 5 had abdominal pain (22%) and 1 showed abdominal distension (4%). In the BCAC group, two patients were without any symptoms (29%), three had abdominal pain (43%), one showed abdominal distension (14%) and one had fever and chills (14%). The cystic lesion size was widely variable; thus, there was no statistical difference (p=0.84). Complete resection was performed in all patients with BCA and BCAC. No tumour recurrence developed in patients with BCA. In patients with BCAC, 1-, 3- and 5-year disease-free survival rates were 100%, 85.7% and 57.1%, respectively, and 1-, 3- and 5-year overall patient survival rates were 100%, 100% and 75.0%, respectively. CONCLUSIONS: It is difficult to distinguish between BCA and BCAC via clinical manifestations and diagnostic imaging findings. Surgical resection is the treatment of choice for BCA and BCAC, and patient prognosis after complete resection was very favourable. PMID- 28989997 TI - Diaphragmatic hernia following liver resection: case series and review of the literature. AB - BACKGROUNDS/AIMS: Postoperative diaphragmatic hernia, following liver resection, is a rare complication. METHODS: Data of patients who underwent major hepatectomy for liver tumors, between 2011 and 2015 were retrospectively reviewed. The literature was searched for studies reporting the occurrence of diaphragmatic hernia following liver resection. RESULTS: Diaphragmatic hernia developed in 2.3% of patients (3/131) with a median delay of 14 months (4-31 months). One patient underwent emergency laparotomy for bowel obstruction and two patients underwent elective diaphragmatic hernia repair. At last follow-up, no recurrences were observed. Fourteen studies including 28 patients were identified in the literature search (donor hepatectomy, n=11: hepatectomy for liver tumors, n=17). Diaphragmatic hernia was repaired emergently in 42.9% of cases and digestive resection was necessary in 28.5% of the cases. One patient died 3 months after hepatectomy, secondary to sepsis, from a segment of small bowel that perforated into the diaphragmatic hernia. CONCLUSIONS: Although rare, diaphragmatic hernia should be considered as an important complication, especially in living donor liver transplant patients. Diaphragmatic hernia should be repaired surgically, even for asymptomatic patients. PMID- 28989998 TI - Mirizzi syndrome: necessity for safe approach in dealing with diagnostic and treatment challenges. AB - BACKGROUNDS/AIMS: The challenging dilemma of Mirizzi syndrome for operating surgeons arises from the difficulty to diagnose it preoperatively, and approximately 50% of cases are diagnosed intraoperatively. In this study, we analysed the effectiveness of diagnostic modalities and treatment options in our series of Mirizzi syndrome. METHODS: Patients had a preoperative or intraoperative diagnosis of Mirizzi syndrome, and were classified into three groups: Group 1: Incidental finding of Mirizzi syndrome intraoperatively (n=34). Group 2: Patients presented with jaundice, diagnosed by endoscopic retrograde cholangiopancreatography (n=17). Group 3: Patients diagnosed initially by ultrasound (n=13). Laparoscopic cholecystectomy was conducted in all 49 patients with Cendes type I disease. Partial cholecystectomy, common bile duct exploration, repair of fistula and t-tube placement was conducted on eight patients with Cendes type II and five patients with Cendes type III. Partial cholecystectomy with Roux-en-Y hepaticojejunostomy was conducted in two patients with Cendes type IV disease. RESULTS: Sixty-four patients were diagnosed with Mirizzi syndrome. Morbidity rate was 3.1%. Mortality rate was 0%. Group 3 (patients diagnosed initially by ultrasound) had the best treatment outcome, the least morbidity, and the shortest hospital stay. CONCLUSIONS: Suspected cases of Mirizzi syndrome should not be underestimated. Difficulty in establishing preoperative diagnosis is the major dilemma. As it is mostly encountered intraoperatively, the approach should be careful and logical to identify the correct type of Mirizzi by a thorough diagnostic laparoscopy and thus, provide optimum treatment for the subtype to achieve the best outcome. PMID- 28989999 TI - Gallstone, cholecystectomy and risk of gastric cancer. AB - BACKGROUNDS/AIMS: The aim of this retrospective study is to compare stomach cancer incidence, characteristics between gallstones, cholecystectomy and control groups. It also aims to investigate key variables' potential effects on overall survival. METHODS: A total of 99 patients, diagnosed with stomach cancers between April 1994 and December 2015, were identified. We excluded stomach cancer patients, accrued during the first year of follow-up in both the gallstones and cholecystectomy groups, assuming that they missed cancers. The main analyses addressing the objective were a chi-square analysis and a survival analysis. RESULTS: The incidence of stomach cancers was increased in both the gallstone and cholecystectomy groups, compared with the control group (p=0.003). Multivariate regression analysis showed that the overall survival in gallstones, cholecystectomy group patients as compared with those in the control group decreased (HR=6.66, 95 CI: 1.94-22.80, p=0.003). Also, T-stage was found to statistically affect the rate of overall survival (HR=9.85, 95% CI: 3.09-31.39, p=.000). The stomach cancer showed the worse survival at the posterior, greater curvature location than anterior, lesser curvature of the stomach. (HR=0.30, 95% CI: 0.11-0.80, p=0.017). CONCLUSIONS: We provided an awareness of the possible increased risks of stomach cancer in gallstone and cholecystectomy group patients, which might be induced by duodenogastric bile reflux. Also, the survival rate was poor (p<0.000). Therefore, close follow-up strategies for early detection are recommended for such patients. PMID- 28990000 TI - Extended pancreatic transection for secure pancreatic reconstruction during pancreaticoduodenectomy. AB - BACKGROUNDS/AIMS: Pancreaticoduodenectomy (PD) is associated with various surgical complications including healing failure of the pancreaticojejunostomy (PJ). This study intended to ensure blood supply to the pancreatic stump through extended pancreatic transection (EPT). METHODS: This study assessed whether EPT reduces PJ-associated complications and whether EPT is harmful on the remnant pancreatic function. The EPT group included 19 patients undergoing PD, pylorus preserving PD (PPPD) or hepatopancreaticoduodenectomy. The propensity score matched control group included 45 patients who had undergone PPPD. Pancreatic transection was performed at the level of the celiac axis in the EPT group, by which the pancreatic body was additionally removed by 3 cm in length comparing with the conventional pancreatic transection. RESULTS: A small invagination fissure suspected as the embryonic fusion site was identified at the ventro caudal edge of the pancreatic body in all patients undergoing EPT. A sizable fissure permitting easy separation of the pancreatic parenchyma was identified in 15 of 19 patients (78.9%). The incidence of significant postoperative pancreatic fistula was significantly lower in the EPT group than in the control group (p=0.047). There was no significant increase in the postoperative de novo diabetes mellitus in EPT group (p=0.60). CONCLUSIONS: The EPT technique contributes to the prevention of major pancreatic fistula without impairing remnant pancreatic function. EPT is feasible for routine clinical application or at least in patients with any known risk of PJ leak. PMID- 28990001 TI - Safety of duodenal ampullectomy for benign periampullary tumors. AB - BACKGROUNDS/AIMS: Surgical resection, such as pancreaticoduodenectomy (PD), is used for treatment of benign periampullary tumors, but high morbidity and mortality resulting from PD can be a huddle. The aim of this study is to suggest a safe and less invasive procedure for treatment of benign periampullary tumors. METHODS: From January 2001 to September 2016, 31 patients with ampulla of Vater (AOV) tumors were reviewed retrospectively. Patients who were confirmed with malignancy through biopsy were excluded, except for one patient with malignancy and multiple underlying diseases. To investigate the safety and availability of transduodenal ampullectomy (TDA), TDA and endoscopic papillectomy (EP) were compared. RESULTS: There was no significant difference in the occurrence of complications between the TDA group and EP group (p=0.145), and the resection margins were negative in both groups. There was no recurrence in patients who had TDA, while one patient had a recurrence after EP. CONCLUSIONS: This study suggests that TDA is as safe as EP for treating benign periampullary tumors. PMID- 28990002 TI - Two cases of ALPPS procedure: simultaneous ALPPS and colorectal resection and ALPPS procedure for hepatic malignancy larger than 15 centimeter. AB - Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has recently been introduced as a new surgical technique to increase future liver remnant in patients with marginal liver volume contemplating major liver resection. We herein present two cases. Case 1: a 68-year-old male patient with colorectal liver metastasis was referred to our department. The future liver remnant (FLR) was 22%. We performed first-stage ALPPS and colorectal surgery concurrently and second stage operation was performed 8 days later. The patient discharged 28 days after the first-stage ALPPS procedure. Case 2: a 69-year-old male patient with a huge hepatic mass was referred for hepatic surgery. The FLR was 19%. After the first stage of the ALPPS procedure, acute renal failure and posthepatectomy liver failure occurred. The patient began to recover on the 5th postoperative day. At 10 days after the first stage, the patient completed the second-stage procedure. The patient discharged 23 days after the first-stage ALPPS procedure. So far many studies are currently underway to identify factors associated with the morbidity and mortality of the ALPPS procedure, it is necessary to continue follow-up studies and observe the results. PMID- 28990003 TI - Liver lesions detected in a hepatitis B core total antibody-positive patient masquerading as hepatocellular carcinoma: a rare case of peliosis hepatis and a review of the literature. AB - Peliosis Hepatis (PH) is a rare vascular disorder of the liver, characterized by the presence of cystic blood-filled cavities distributed throughout the hepatic parenchyma. The pathogenesis of PH remains controversial. The preoperative diagnosis of PH is difficult, due to the non-specific imaging characteristics of PH and almost all cases are diagnosed on histology post resection. This study presents a case of PH masquerading as hepatocellular carcinoma (HCC). The patient is a 45-year old Chinese lady, who presented with transaminitis. She was found to be hepatitis B virus core total antibody-positive with an alpha-fetoprotein (AFP) of 29.4 ng/ml. Triphasic liver computed tomography showed several arterial hypervascular lesions and hypoenhancing lesions on the venous phase, particularly in the segments 6/7. Subsequently, a magnetic resonance imaging scan showed multiple lesions in the right hemiliver with an indeterminate enhancement patterns. Subsequently, she decided to undergo a resection procedure. Histopathology revealed findings consistent with PH with some unusual features. This case demonstrates a clinical conundrum, in which PH presented with a raised AFP, in a patient with risk factors for the development of HCC. The clinical suspicion of PH should be high in patients, who present with multiple hepatic lesions with variable enhancement patterns. PMID- 28990004 TI - Primary hepatic lymphoma treated with liver resection followed by chemotherapy: a case report. AB - Non-Hodgkin lymphoma often involves the liver. However, primary hepatic lymphoma (PHL) confined to the liver without evidence of lymphomatous involvement is rare. The optimal therapy for PHL is still unclear. Most patients present with poor prognostic features. Here, we report a case of PHL treated with liver resection followed by chemotherapy. A 65-year-old male was referred for further evaluation about a liver mass detected on ultrasound. Abdominal computed tomography (CT) scan showed well-defined single mass of 6 cm in diameter. Positron emission tomography/CT scan revealed a hot uptake lesion on the segment 8 of the liver. Colonoscopy showed no abnormal finding. It was diagnosed as intrahepatic cholangiocarcinoma. A right anterior sectionectomy was performed. Postoperative pathology revealed diffuse large B-cell lymphoma. Bone marrow biopsy showed normal findings. The final diagnosis was confirmed as PHL. The patient subsequently received six cycles of R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisolone) regimen. The patient is doing well without relapse after 60 months of follow-up. Because of its rarity and the lack of specific laboratory, radiological, or clinical finding, liver biopsy is essential for definite diagnosis of PHL. Optimal treatment for PHL is currently uncertain. However, surgical resection followed by adjuvant chemotherapy should be considered for select individuals to achieve better outcome. PMID- 28990006 TI - Distal pancreatectomy for pancreatic arteriovenous malformation: report of a case. AB - Arteriovenous malformation (AVM) of the pancreas is an uncommon disease, which can cause an abdominal pain. This disease is characterized by a tangled vascular network, including the whole or part of the pancreas, resulting in portal hypertension by forming a shunt of the pancreas arteries to drain directly into the portal venous system. This study presents a case that was suspected as AVM of the pancreas by preoperative contrast-enhanced computed tomography scan (CT). A 49-year-old male patient had several episodes of abdominal discomfort associated with dyspepsia for 4 days. Magnetic resonance imaging showed enhancement of the conglomeration about 1.5 cm size in diameter in the pancreas. Selective angiography showed the proliferation of a vascular network in the pancreas and an early visualization of the portal vein during the arterial phase. Distal pancreatectomy with splenectomy was done. Histology of the pancreas showed AVM, with enzymatic fat necrosis extending to the capsule of the pancreas. The patient recovered successfully without postoperative complications. Surgical resection of pancreas is the definitive treatment for symptomatic AVM. PMID- 28990005 TI - Small cell carcinoma of the gallbladder: a case report. AB - Small cell carcinoma (SCC) of the gallbladder is an extremely rare tumor. Despite aggressive and varied treatments, its prognosis is poor. A 70-year-old woman undergoing treatment for pneumonia was detected with a gallbladder mass. Radical cholecystectomy was performed and the pathology revealed small cell carcinoma. There were metastases in 2 lymph nodes, scoring T2N1M0, stage IIIB (AJCC 7th). The patient has survived thus far, with subsequent chemotherapy. SCC of the gallbladder has an extremely low incidence and poor prognosis. In some cases, radical surgery with chemotherapy or radiation therapy could increase survival rate of patients. PMID- 28990007 TI - Pancreatic resection for renal cell carcinoma metastasis: a case review. AB - Renal cell carcinoma (RCC) is the most common type of kidney malignancy. The pancreas is an infrequent site of metastasis in relation to any type of malignancy. However, RCC is one of the tumor types that most frequently metastasize to the pancreas. In this study, we report our experiences with two patients who underwent pancreatic resection for metastatic RCC tumors; of these two patients, one patient had a tumor was a metachronous pancreas-only tumor, and the other patient's tumor was synchronous with hematogenous lung metastasis. Following left-side pancreatic resection, the patients were administered tyrosine kinase inhibitors. PMID- 28990009 TI - Education as Liberation? AB - This paper studies the political and social impacts of increased education by utilizing a randomized girls' merit scholarship programme in Kenya that raised test scores and secondary schooling. Consistent with the view that education empowers the disadvantaged to challenge authority, we find that the programme reduced the acceptance of domestic violence and political authority. Young women in programme schools also increased their objective political knowledge. We find that this rejection of the status quo did not translate into greater perceived political efficacy, community participation or voting intentions. Instead, there is suggestive evidence that the perceived legitimacy of political violence increased. PMID- 28990008 TI - Parcellation of Human Amygdala Subfields Using Orientation Distribution Function and Spectral K-means Clustering. AB - Amygdala plays an important role in fear and emotional learning, which are critical for human survival. Despite the functional relevance and unique circuitry of each human amygdaloid subnuclei, there has yet to be an efficient imaging method for identifying these regions in vivo. A data-driven approach without prior knowledge provides advantages of efficient and objective assessments. The present study uses high angular and high spatial resolution diffusion magnetic resonance imaging to generate orientation distribution function, which bears distinctive microstructural features. The features were extracted using spherical harmonic decomposition to assess microstructural similarity within amygdala subfields are identified via similarity matrices using spectral k-mean clustering. The approach was tested on 32 healthy volunteers and three distinct amygdala subfields were identified including medial, posterior superior lateral, and anterior-inferior lateral. PMID- 28990010 TI - Concepts, Terms, and Mental Models: Everyday Challenges to Older Adult Social Media Adoption. AB - Social connection and social support are strong predictors of wellbeing, but maintaining social relations often becomes more difficult at older ages. Because social media enhance feelings of connectedness and reduce feelings of loneliness, they may present accessible and relatively low cost mechanisms to enhance life quality at older ages. Using data gathered from two focus groups of potential older adult social media learners, we explored the physical and cognitive challenges to social media use, perceptions of social media benefits, and conceptual barriers to use. Findings support earlier studies that identify perceived benefit as important to social media adoption at older ages, and extend these by identifying that a lack in conceptual knowledge of these technologies is an additional barrier to use. We then discuss the cognitive implications of gaining this knowledge. PMID- 28990011 TI - How Gamification Affects Physical Activity: Large-scale Analysis of Walking Challenges in a Mobile Application. AB - Gamification represents an effective way to incentivize user behavior across a number of computing applications. However, despite the fact that physical activity is essential for a healthy lifestyle, surprisingly little is known about how gamification and in particular competitions shape human physical activity. Here we study how competitions affect physical activity. We focus on walking challenges in a mobile activity tracking application where multiple users compete over who takes the most steps over a predefined number of days. We synthesize our findings in a series of game and app design implications. In particular, we analyze nearly 2,500 physical activity competitions over a period of one year capturing more than 800,000 person days of activity tracking. We observe that during walking competitions, the average user increases physical activity by 23%. Furthermore, there are large increases in activity for both men and women across all ages, and weight status, and even for users that were previously fairly inactive. We also find that the composition of participants greatly affects the dynamics of the game. In particular, if highly unequal participants get matched to each other, then competition suffers and the overall effect on the physical activity drops significantly. Furthermore, competitions with an equal mix of both men and women are more effective in increasing the level of activities. We leverage these insights to develop a statistical model to predict whether or not a competition will be particularly engaging with significant accuracy. Our models can serve as a guideline to help design more engaging competitions that lead to most beneficial behavioral changes. PMID- 28990012 TI - Impact of endoscopic sinus surgery on otologic symptoms associated with chronic rhinosinusitis. AB - OBJECTIVE: To evaluate improvements in otologic symptoms after endoscopic sinus surgery (ESS) in patients with chronic rhinosinusitis (CRS), and identify differences in symptoms, if any, between CRS patients with (CRSwNP) and without (CRSsNP) nasal polyposis. STUDY DESIGN: Prospective multi-center observational cohort study. SETTING: Academic tertiary medical centers. SUBJECTS AND METHODS: Adults with medically recalcitrant CRS who elected ESS were enrolled in a prospective, multi-center, observational cohort study between March, 2011 and October, 2014. Preoperative evaluation of subjects included assessment of clinical characteristics, measures of disease severity, and quality of life evaluation using the 22-item SinoNasal Outcome Test (SNOT-22). Postoperative improvement in otologic symptoms (ear fullness, dizziness, ear pain) scores were evaluated and compared between CRSwNP and CRSsNP subgroups. RESULTS: 395 study patients completed both preoperative and postoperative evaluations, with an average follow-up of 13.9 months after ESS. The prevalence of patients reporting at least one otologic symptom preoperatively (87%) significantly decreased after ESS (63%; p<0.001). Significant postoperative improvement across all otologic scores was also reported (p<0.001). Relative mean improvement in otologic symptom severity was similar for both CRSwNP and CRSsNP, except patients with CRSwNP reported significantly greater postoperative improvement in ear fullness compared to CRSsNP (54% vs. 41%; p=0.039). A total of 61%, 44%, and 43% of patients reported experiencing improvement in "ear fullness", "dizziness" and "ear pain", respectively. CONCLUSION: Sinus surgery significantly improves otologic symptoms associated with CRS. CRSwNP patients reported slightly greater relief of ear fullness than CRSsNP patients following ESS. PMID- 28990013 TI - Primary oral melanoma: A clinicopathologic review and case presentation. AB - OBJECTIVE: The purpose of this manuscript is to present a clinicopathologic review of the literature concerning all the detailed cases of primary oral melanoma (OM) that were confirmed by immunohistochemistry. In addition, a pertinent case presentation is addressed. DATA SOURCES: An extensive electronic search of the literature was performed using PubMed/Medline from 1953 to 2017. Relevant articles were selected based on specific inclusion criteria. Statistical analyses were conducted by the Shapiro-Wilk, Fisher's exact, chi-square, and Z tests (alpha = .05). RESULTS: Forty-nine cases of primary OM reported in the literature plus the current case were analyzed; patient ages ranged from 17 to 89 years with a mean of 60.8 years; male to female ratio was 1.5:1; Caucasian patients were the most affected and the most frequent locations were maxillary alveolar mucosa and palate; the majority of the lesions were pigmented (62%); differences among the proportions of positivity to S-100, HMB-45, Melan-A, NKFC3, vimentin, tyrosinase, CK, microphthalmia transcription factor (MITF), and Ki-67 were found (P < .0001), especially when comparing with vimentin (P < .05) and CK (P < .01); recurrence was reported in 11.6% and mortality in 54.8%. The case presented is of a 71-year-old mixed-race woman who presented multiple pigmented lesions over the maxillary alveolar mucosa and palate. Positivity for S-100, HMB 45, Melan-A, and Ki-67 confirmed the diagnosis of primary OM. CONCLUSION: Primary OM is rare and very aggressive, with only 49 detailed cases confirmed by immunohistochemistry existing within the English literature, in addition to the present case. S-100 and HMB-45 are excellent markers to confirm the diagnosis of primary OM, although the use of adjuvant specific markers such as Melan-A, tyrosinase, and MITF should be also encouraged. PMID- 28990014 TI - Atypical root resorption following root fractures in primary teeth. AB - Atypical root resorption (ARR) is the condition of a superficial and circumferential resorption process along the lateral and/or apical root surface of a primary maxillary incisor. This case series demonstrates longitudinal observations of six patients with atypical root resorption following root fractured primary incisors. The characteristics of atypical root resorption were different from pathologic root resorption. PMID- 28990015 TI - Efficacy of the twin block, a peripheral nerve block for the management of chronic masticatory myofascial pain: A case series. AB - Masticatory myofascial pain is the one of the most common etiologies for nonodontogenic pain, often characterized by the presence of trigger points. Conventional management includes approaches such as jaw exercises, physical therapy, intraoral appliances, medications, and trigger point injections. Peripheral/regional nerve blocks have shown to be effective in managing myogenous pain conditions. The twin block is a nerve block that blocks both the masseteric and the anterior deep temporal nerves. The objective of this case series is to illustrate expeditious and sustained efficacy of the twin block in the management of chronic masticatory myofascial pain. PMID- 28990016 TI - Orthodontics and the temporomandibular joint: What orthodontic providers need to know. AB - Currently, there are three major groups of dentists who provide orthodontic services to the public: postgraduate trained orthodontists, postgraduate trained pediatric dentists, and general dentists who have taken various orthodontic training courses. All of them can expect to encounter a variety of clinical situations that require a proper understanding of how normal temporomandibular joints (TMJs) function, and also how the masticatory system can develop pain dysfunction problems; those problems are classified and defined as temporomandibular disorders (TMDs). In this paper, six "intersections" between these groups of practitioners and those clinical situations will be discussed, with an emphasis on practical approaches to managing problems that may arise during orthodontic treatment. Specific recommendations are offered to help clinicians recognize clinical problems and to deal with them successfully. PMID- 28990017 TI - Associations between patients' understanding of periodontal disease, treatment compliance, and disease status. AB - OBJECTIVE: The aim of the present study was to investigate the associations between patients' understanding of periodontal disease, their individual compliance to homecare, self-reported periodontal disease, and how they have been educated regarding their oral health. METHOD AND MATERIALS: A cross-sectional study was performed by distributing questionnaires to patients at the University of Alberta Dental Clinic. A survey consisting of 45 questions was constructed in order to quantify patients' understanding of periodontal disease (section 1), where they received their information, how often they have been instructed by dental practitioners, their homecare habits (section 2), and their self-reported periodontal status (section 3). RESULTS: In total, 286 surveys were analyzed from participants (92 males; 191 females; 3 other), with an age range of 15-87 years (mean 42.6 +/- 15.1). Correctly answered questions ranged from 39.5% to 95.8%, the highest related to smoking and lowest regarding gingival pockets. Only 42.0% and 42.7% understood the purpose of periodontal probing and the difference between gingivitis and periodontitis respectively. Of the participants, 13.3% and 54.2% had never been shown how to clean their teeth or counselled regarding dietary habits from dental professionals respectively, and only 24.8% had been shown more than four times how to clean their teeth. A moderate association was found between sections 1 (knowledge) and 2 (habits/instruction), between sections 1 and 3 (self-reported health), and between sections 2 and 3. CONCLUSION: Moderate association between knowledge, homecare habits, instruction from dental professionals, and self-reported periodontal health was found. Patient understanding is lacking in certain areas and there seems to be a lack of patient education from dental professionals. As dental professionals improve patient instruction, there may be an improvement in patient compliance to homecare and periodontal health. PMID- 28990018 TI - Crystallographic features of poly(vinylidene fluoride) film upon an attractive substrate of KBr. AB - Among all the polymorphs of poly(vinylidene fluoride) (PVDF), the polar gamma form possesses the highest melting point and electrical breakdown strength as well as the strongest solvent and irradiation resistance, which are beneficial for the durability of PVDF products. Since the gamma-form is neither kinetically favorable nor the most thermodynamically stable, it is still difficult to attain the exclusive gamma-polymorph, particularly in the case of neat PVDF. In this study, the melt isothermal crystallization of PVDF films was carried out between two KBr wafers. Owing to the characteristics of KBr wafer, including no IR absorbance and high optical transmittance, the crystallographic features originating from the KBr substrate can be conveniently elucidated through the in situ inspected techniques of FTIR and PLM. The KBr wafers significantly accelerated the crystallization kinetics of alpha-crystals, and then readily triggered the solid-state alpha- to gamma-transformation of the pre-formed alpha spherulites, resulting in a 10 MUm-thick, neat PVDF film with an absolute crystallinity of 35% and a relative gamma fraction as high as 94%. When the film thickness was increased to 40 MUm, the crystallization rate of the alpha-form was still rapid, but the solid-state transformation was not appreciable. These interesting crystallographic phenomena are attributed to the existence of ion dipole interaction between the -CF2 or -CH2 of PVDF chains and the surface of KBr wafer. Unlike most traditional substrate-dominated crystallizations that prevail in a surface epitaxy manner, in which the target films are of ultra-thin thickness (of the order of 10 nm), the ion-dipole interaction promotes the effective thickness to a ten micron level, which enables its production and application at scalable level. Moreover, the triggering of alpha- to gamma transformation via external fields could be an alternative for achieving the gamma-dominant PVDF products, particularly when the introduction of external additives is prohibited. PMID- 28990019 TI - Liquid-based stationary phase for deterministic lateral displacement separation in microfluidics. AB - Deterministic lateral displacement (DLD) is a promising separation scheme in microfluidic systems. In traditional DLD, a periodic array of solid posts induces the separative migration of suspended particles moving through the system. Here, we present a radical departure from traditional DLD systems and use an array of anchored liquid-bridges as the stationary phase in the DLD device. The liquid bridges are created between two parallel plates and anchored to the bottom one by cylindrical wells. We show that the non-linear particle dynamics observed in traditional DLD systems is also present in the anchored-liquid case, enabling analogous size-based separation of suspended particles. The use of liquid-bridges as the stationary phase presents additional possibilities in separation technologies, potentially eliminating or significantly reducing clogging, enabling renewable and/or reconfigurable systems, allowing a different set of fabrication methods and providing alternative ways to separate particles based on their interaction with liquid-liquid interfaces. Some of these advantages could also extend to filtration methods based on similar liquid-based stationary phases. PMID- 28990020 TI - Proton relays in anomalous carbocations dictate spectroscopy, stability, and mechanisms: case studies on C2H5+ and C3H3. AB - We present a detailed analysis of the anomalous carbocations: C2H5+ and C3H3+. This work involves (a) probing electronic structural properties, (b) ab initio dynamics simulations over a range of internal energies, (c) analysis of reduced dimensional potential surfaces directed along selected conformational transition pathways, (d) dynamically averaged vibrational spectra computed from ab initio dynamics trajectories, and (e) two-dimensional time-frequency analysis to probe conformational dynamics. Key findings are as follows: (i) as noted in our previous study on C2H3+, it appears that these non-classical carbocations are stabilized by delocalized nuclear frameworks and "proton shuttles". We analyze this nuclear delocalization and find critical parallels between conformational changes in C2H3+, C2H5+, and C3H3+. (ii) The vibrational signatures of C2H5+ are dominated by the "bridge-proton" conformation, but also show critical contributions from the "classical" configuration, which is a transition state at almost all levels of theory. This result is further substantiated through two dimensional time-frequency analysis and is at odds with earlier explanations of the experimental spectra, where frequencies close to the classical region were thought to arise from an impurity. While this is still possible, our results here indicate an additional (perhaps more likely) explanation that involves the "classical" isomer. (iii) Finally, in the case of C3H3+ our explanation of the experimental result includes the presence of multiple, namely, "cyclic", "straight", and propargyl, configurations. Proton shuttles and nuclear delocalization, reminiscent of those seen in the case of C2H3+, were seen all through and have a critical role in all our observations. PMID- 28990021 TI - Ultrafast X-ray absorption study of longitudinal-transverse phonon coupling in electrolyte aqueous solution. AB - Ultrafast X-ray absorption spectroscopy is applied to study the conversion of longitudinal to transverse phonons in aqueous solution. Permanganate solutes serve as X-ray probe molecules that permit the measurement of the conversion of 13.5 GHz, longitudinal phonons to 27 GHz, transverse phonons that propagate with high-frequency sound speed. The experimental results, combined with QM/MM MD simulations, show that the hydrogen bond network around the charged solutes has a glass-like stiffness that persists for at least tens of picoseconds. PMID- 28990022 TI - Giant anisotropic photogalvanic effect in a flexible AsSb monolayer with ultrahigh carrier mobility. AB - Searching for novel two-dimensional (2D) materials with desirable properties is of great significance for the design of next generation nano-devices. In this work, we address the electronic and optoelectronic properties of monolayer AsSb on the basis of density functional theory (DFT) combined with quantum transport simulations. We find three stable phases of monolayer AsSb, that is, the alpha, gamma and epsilon phases, and all of them show direct bandgaps, which are beneficial in increasing the transition probability of photon-generated electrons and improving the efficiency of photoelectric conversion. In addition, these systems could attain meaningful strain-induced band engineering and a phase transition from semiconductor to metal occurs. It is highly interesting that the monolayer AsSb has an ultrahigh carrier mobility (~104 cm2 V-1 s-1), which is evidently larger than most of the reported 2D materials. In light of the nonequilibrium Green's function formalism, a linear photogalvanic effect (PGE) is observed along both the zigzag and armchair directions, suggesting that monolayer AsSb exhibits excellent photoresponse in a broad spectrum ranging from ultraviolet to infrared light, which is favorable for serving as a potential outstanding photovoltaic material. Our results highlight that these monolayer AsSb are promising candidates for future applications in electronics and optoelectronics. PMID- 28990023 TI - Controlled droplet discretization and manipulation using membrane displacement traps. AB - An innovative platform enabling complex discretization and manipulation of aqueous droplets is described. The system uses simple membrane displacement trap elements to perform multiple functions including droplet discretization, release, metering, capture, and merging. Multi-layer PDMS devices with membrane displacement trap arrays are used to discretize sample into nanoliter scale droplet volumes, and reliably manipulate individual droplets within the arrays. Performance is characterized for varying capillary number flows, membrane actuation pressures, trap and membrane geometries, and trapped droplet volumes, with operational domains established for each platform function. The novel approach to sample digitization and droplet manipulation is demonstrated through discretization of a dilute bacteria sample, metering of individual traps to generate droplets containing single bacteria, and merging of the resulting droplets to pair the selected bacteria within a single droplet. PMID- 28990024 TI - Visible-light promoted gamma-cyanoalkyl radical generation: three-component cyanopropylation/etherification of unactivated alkenes. AB - A photoredox approach to generate distal cyano-substituted alkyl radicals through C-C bond cleavage of cyclobutanone oximes was developed. The radicals produced by this method were applied to three-component cyanopropylation/etherification of unactivated alkenes. Their reactions with diverse radical acceptors were also demonstrated. PMID- 28990025 TI - An exploding N-isocyanide reagent formally composed of anthracene, dinitrogen and a carbon atom. AB - Targeted as an example of a compound composed of a carbon atom together with two stable neutral leaving groups, 7-isocyano-7-azadibenzonorbornadiene, CN2A (1, A = C14H10 or anthracene) has been synthesized and spectroscopically and structurally characterized. The terminal C atom of 1 can be transferred: mesityl nitrile oxide reacts with 1 to produce carbon monoxide, likely via intermediacy of the N isocyanate OCN2A. Reaction of 1 with [RuCl2(CO)(PCy3)2] leads to [RuCl2(CO)(1)(PCy3)2] which decomposes unselectively: in the product mixture, the carbide complex [RuCl2(C)(PCy3)2] was detected. Upon heating in the solid state or in solution, 1 decomposes to A, N2 and cyanogen (C2N2) as substantiated using molecular beam mass spectrometry, IR and NMR spectroscopy techniques. PMID- 28990026 TI - Correction: Tailoring of optical properties of fluorescein using green synthesized gold nanoparticles. AB - Correction for 'Tailoring of optical properties of fluorescein using green synthesized gold nanoparticles' by Jisha John et al., Phys. Chem. Chem. Phys., 2015, 17, 15813-15821. PMID- 28990027 TI - A DFT study on the mechanism of photoselective catalytic reduction of 4 bromobenzaldehyde in different solvents employing an OH-defected TiO2 cluster model. AB - Density functional theory calculations are employed to study the mechanism of photoselective catalytic reduction of 4-bromobenzaldehyde (4-BBA) in acetonitrile and in ethanol solvents. A totally relaxed Ti3O9H6 cluster model is proposed to represent titanium dioxide (TiO2) surfaces. The reduction selectivity of an adsorbed 4-BBA molecule on Ti3O9H6 has been investigated. Owing to the difference in the proton and H atom donating capabilities between explicit CH3CN and C2H5OH solvent molecules, the photocatalytic reduction of 4-BBA is the debromination process in acetonitrile, whereas in ethanol it is the carbonyl reduction process. Therefore 4-BBA can be selectively reduced to benzaldehyde in acetonitrile and 4 bromobenzyl alcohol in ethanol, respectively. Our computational results have verified the reaction mechanism proposed by experiments and show that the debromination of 4-BBA would be efficient if both 4-BBA and Ti3O9H6 have an extra photoelectron. The Ti3O9H6 cluster, playing a role as a hydrogen source and a bridge to transfer photoelectrons from bulk TiO2, would have potential to be an ideal molecular model for understanding photocatalytic reactions on the TiO2 surface. PMID- 28990028 TI - A unimolecular channel formed by dual helical peptide modified pillar[5]arene: correlating transmembrane transport properties with antimicrobial activity and haemolytic toxicity. AB - Five unimolecular channels with different lengths are presented. The varying length of these channels has significant impact on their transmembrane transport properties, which are directly correlated with their antimicrobial activity and inversely correlated with their haemolytic toxicity. By further structural optimization, these new channels could reach high antimicrobial activity and very low haemolytic toxicity, with the potential to serve as systemic antibiotics. PMID- 28990029 TI - Highly sensitive detection of epidermal growth factor receptor in lung cancer cells by aptamer-based target-/probe-mediated cyclic signal amplification. AB - We develop an antibody-free fluorescence method for the epidermal growth factor receptor (EGFR) assay using aptamer-based target-/probe-mediated cyclic signal amplification. The method is highly sensitive with a detection limit of 0.16 fM, and it can be applied to detect EGFR in lung cancer cells, holding great potential in clinical diagnosis. PMID- 28990030 TI - Intermolecular magnetic interactions in stacked DNA base pairs. AB - The influence of pi-stacking on the magnetic properties of atoms that belong to adenine-thymine and guanine-cytosine pairs in sequences of three and five layers of DNA base pairs was analysed. As probes we used NMR spectroscopic parameters, which are among the most useful tools to learn about the transmission of magnetic interactions in molecules. Four DFT functionals were employed: B3LYP, BHANDLYP, KT2 and KT3, together with the SOPPA method. Besides, given that the number of non-hydrogen atoms of the supramolecular systems studied here is larger than 50 we applied a locally dense basis set scheme. Our results show that the piling up of a few Watson-Crick base pairs above and below a given pair modifies its NMR spectroscopic parameters by an amount that may be measurable and the percentage of variation does not depend on dispersion. We found that magnetic shieldings are more sensitive than J-couplings, and also that some atoms are more sensitive than others. Stacking affects the shielding of non-hydrogen atoms like nitrogens, that are donors in hydrogen bonds, HBs, and the carbons bonded to them. The amount of variation of these shieldings was found to be from 2% to 5% when the pairs are considered first as isolated, and then, placed in the middle of a sequence of three layers of base pairs. Such a variation becomes vanishingly small when the sequence contains more than three layers, showing that the stacking effect on NMR spectroscopic parameters has a local nature. We have also found a pattern for shieldings. First, equivalent atoms of similar monomers (thymine and adenine, or guanine and cytosine) have similar values of absolute shieldings in isolated pairs, and the amount of variation from isolated pairs to aggregates of a few pairs is also similar, meaning that equivalent atoms are affected in a similar manner by pi-stacking. Second, the hydrogen atoms which belong to hydrogen bonds are more sensitive to the piling up than the non-hydrogen atoms. PMID- 28990031 TI - Topology vs. thermodynamics in chemical reactions: the instability of PH5. AB - The topological approach, based on Bader theory, is compared to the common thermodynamical methodology to study chemical reactivity. It is shown how the former indeed has numerous advantages and provides a more detailed description with respect to the latter about the course of the reaction. The comparison between the two approaches is performed by considering a classical reaction, i.e. the decomposition of PX5 (X = H, F). The topological investigation was supported by using different state-of-the-art topological tools, such as the source function, Espinosa indexes, delocalisation indexes, and domain-averaged Fermi hole analysis. Furthermore, in this work a new topological descriptor, the Bader energy density, PBADER, is introduced and applied to the study case. For the first time since Bader theory was introduced, the distribution of atomic energies in the atomic basins was analysed in detail and used to explain the chemical reactivity a priori. PMID- 28990033 TI - Controlled direct electron transfer kinetics of fructose dehydrogenase at cup stacked carbon nanofibers. AB - Graphene edge sites not only facilitate heterogeneous electron transfer reactions of redox species because of localization of electrons, but also allow sensitivities and selectivities to be tuned by controlling the atomic oxygen/carbon (O/C) ratio. Here, we immobilized fructose dehydrogenase (FDH) onto the surface of cup-stacked carbon nanofibers (CSCNFs), which provide highly ordered graphene edges with a controlled O/C ratio, and investigated the direct electron communication with FDH. As the O/C ratio decreased at the CSCNF surface, the negative zeta potential was mitigated and the electrochemical communication with FDH was facilitated. This is likely due to improved orientation of FDH molecules on the CSCNF surface. CSCNFs with a controlled O/C ratio could be applied to FDH-based d-fructose biosensors with tunable dynamic range and fructose biofuel cells with a controlled maximum current. PMID- 28990032 TI - Impact of multiple quaternary ammonium salts on dynamic properties of BSA adsorption layer at different pH values. AB - The interaction mechanism of multiple quaternary ammonium salts (MQAS) with bovine serum albumin (BSA) was examined by the fluorescence quenching method and circular dichroism (CD) spectra. Moreover, the effects of MQAS on the dynamic properties of BSA adsorption layers at different pH values were investigated using dilational interfacial rheology. Results show that the quenching constants increase with an increase in pH values and decrease with an increase in the experiment temperature at pH 5.3. The quenching mechanism is static quenching, and the electrostatic force dominates the interaction between MQAS and BSA at pH 5.3. Due to three positive head groups, MQAS can significantly affect the dynamic interfacial activity of BSA molecules at a relatively low concentration. At pH 4.3, the electrostatic repulsion is unfavorable for the formation of MQAS/BSA complexes. Consequently, MQAS molecules will replace BSA molecules from the interface by competitive adsorption. At the pH value above the isoelectric point of BSA, the electrostatic attraction is better for the formation of MQAS/BSA complexes, which exhibit a rapid adsorption rate and an enhanced interfacial activity. Moreover, the kinetic dependencies of interfacial dilational elasticity for the MQAS/BSA mixtures become nonmonotonous. The appearance of the maximum interfacial elasticity values can be attributed to the formation of tails and loops, which suggests that the addition of MQAS destroys the secondary and tertiary structure of protein in the bulk phase. In addition, the effects of MQAS on the secondary structure of protein were demonstrated by CD spectra. PMID- 28990034 TI - Theoretical illumination of highly original photoreactive 3MC states and the mechanism of the photochemistry of Ru(ii) tris(bidentate) complexes. AB - We have identified highly novel photoreactive 3MC states of ruthenium(ii) 4,4'-bi 1,2,3-triazolyl (btz) complexes of the form [Ru(N^N)(btz)2]2+ and have elucidated the mechanism of the highly unusual experimental observations of photochemical ligand dechelation and concomitant ligand rearrangement reactivity to form unusual photoproducts trans-[Ru(N^N)(kappa2-btz)(kappa1-btz)(solvent)]2+. The triplet metal-to-ligand charge-transfer (3MLCT) states and classical Jahn-Teller type triplet metal-centred (3MC) states of the series of complexes [Ru(N^N)3 n(btz)n]2+ (btz = 4,4'-bi-1,2,3-triazolyl; N^N = 2,2'-bipyridyl (bpy), n = 0 (1), 1 (2), 2 (3), 3 (5); N^N = 4-(pyrid-2-yl)-1,2,3-triazole (pytz), n = 1 (4)) have been optimised by density functional theory (DFT) and characterised. There is a gradual and significant destabilisation of the 3MLCT states as the triazole content of the complexes increases, which occurs with a slight stabilisation of the 3MC states. Whilst consistent with the promotion of photochemical reactivity in the heteroleptic complexes of the series relative to 1, these classical 3MC states fail to account for the extraordinary ligand rearrangement processes that accompany ligand ejection. Thorough theoretical exploration of the lowest excited triplet potential energy surface (3PES) here reveals the existence of a new type of 3MC state and the role it plays in the photochemical reactivity of the complexes. This newly discovered state, called MC(F), displays a flattened geometry (indicated by the 'F' in the parentheses) which makes it clearly on the path to achieving the coplanarity of the bidentate ligands in the experimentally observed trans-photoproduct. Further novel 'pentacoordinate' 3MC states with coplanar bidentate ligands, called MC(P) (where the 'P' in the parentheses denotes the pentacoordinate character), were then identified and optimised. The energy barriers between the different triplet states were confirmed to be small which makes all triplet states accessible. Solvent trapping, which occurs on the singlet PES according to Wigner's rules, is finally achieved by a singlet pentacoordinate species to yield the monosolvento photoproduct. Thus, our calculations not only reveal highly novel 3MC states but more significantly demonstrate their crucial role in the formation of the experimentally observed photoproducts. PMID- 28990035 TI - meso-to-meso 2,5-Pyrrolylene bridged zig-zag porphyrin arrays. AB - meso-to-meso 2,5-Pyrrolylene bridged zig-zag porphyrin arrays have been synthesized via a stepwise Suzuki-Miyaura cross coupling reaction. Both the dimeric and trimeric structures of ZnII porphyrin were confirmed by X-ray diffraction analysis. DFT calculations indicate that the porphyrin oligomers are all in zig-zag conformations. The UV/Vis absorption and emission spectra of these porphyrin oligomers were red-shifted as the number of their porphyrin units increased. PMID- 28990036 TI - Silver-mediated oxidative C-H difluoromethylation of phenanthridines and 1,10 phenanthrolines. AB - A silver-mediated oxidative difluoromethylation of phenanthridines and 1,10 phenanthrolines with TMSCF2H is disclosed. This C-H difluoromethylation of N containing polycyclic aromatics constitutes an efficient method for the regioselective synthesis of difluoromethylated N-heterocycles. PMID- 28990037 TI - Spreading dynamics of a precursor film of nanodrops on total wetting surfaces. AB - The spreading dynamics of a nanodrop on a total wetting surface is explored by many-body dissipative particle dynamics. Both smooth and rough surfaces with various spreading coefficients (S) are considered. The evolution of the spreading film is mainly characterized by the radius of the wetting area (Rp) and the apparent base radius (Rb) and the contact angle (theta) of the spherical cap. The difference between Rp and Rb reveals the presence of the precursor film. The dynamic behavior can be described by the power law: Rp ~ tm, Rb ~ tn, and theta ~ t-alpha. Regardless of the surface roughness, the exponents n = 0.1 and alpha = 0.3 agree with Tanner's law and are independent of the spreading coefficient. However, the expansion of the precursor film depends on the surface roughness and the spreading coefficient. As the cavity size corresponding to the roughness decreases or S increases, the exponent m can rise approximately from 0.1 to 0.2. That is, the spontaneous expansion is driven by the spreading coefficient but impeded by the surface roughness. Forced spreading of a nanodrop on a smooth surface leads to anisotropic expansion. The length along the force direction L(t) follows the power law L ? tp and the exponent p ~ 0.274 is insensitive to S. Nonetheless, the length along the direction perpendicular to the force direction is dominated by the spontaneous spreading. Contact line pinning of the rear end is only observed for intermediate forces. PMID- 28990038 TI - An Ir-photoredox-catalyzed decarboxylative Michael addition of glyoxylic acid acetal as a formyl equivalent. AB - We reported herein an iridium-photoredox-catalyzed decarboxylative conjugated addition of glyoxylic acid acetals with various Michael acceptors, including unsaturated amide, ester, aldehyde, ketone, and nitrile under irradiation. Vinyl pyridine and alpha-aryl styrene are also suitable substrates. The reaction offers various types of acetal products, which are of synthetic significance as protected aldehydes. PMID- 28990039 TI - Size and shape evolution of highly magnetic iron nanoparticles from successive growth reactions. AB - We present a synthetic protocol for the solution-phase synthesis of monocrystalline, metallic iron nanoparticles based on seed-mediated growth, showing near-single nanometre control over particle size. A shape evolution to cubic nanoparticles is also observed with increasing size. Magnetic properties were measured after surface oxidation, showing the potential of our protocol to tune the magnetism of iron nanoparticles for applications requiring superparamagnetic or ferromagnetic nanoparticles. PMID- 28990040 TI - Squeezing bio-capsules into a constriction: deformation till break-up. AB - We study experimentally the deformation and break-up of liquid-filled capsules trapped at an axisymmetric step constriction, and subjected to increasing pressure drops. We considered biological (trout fish eggs) and bioartificial (made of ovalbumin and alginate) ones, with the objective to characterize the transition to break-up. We find that both capsule populations behave as a brittle material. They do not exhibit any plastic deformation prior to break-up. Moreover critical pressure drop exhibits a stochastic behavior as known for the fracture of disordered media. The break-up probability follows a three-parameter Weibull distribution, from which one can deduce the capsule rupture characteristics. PMID- 28990041 TI - Brain iron deposition analysis using susceptibility weighted imaging and its association with body iron level in patients with mild cognitive impairment. AB - The aim of the present study was to analyze brain and body iron levels among patients with mild cognitive impairment (MCI), Alzheimer's disease (AD), and normal controls (NCs). A total of 90 participants (30 MCI, 30 AD, 30 NC) were enrolled. Brain iron content was quantified using susceptibility weighted imaging (SWI). Phase values were used to calculate bilateral iron content in the hippocampus (HP), substantia nigra, red nucleus (RN), dentate nucleus (DN), caudate nucleus (CN), globus pallidus (GP), putamen (PUT), frontal white matter, temporal cortex (TC), and parietal cortex. Body iron indices, including serum iron, serum transferrin, ferritin and total iron binding capacity, were measured. Phase values of the left (L)-DN, L-CN, and bilateral PUT in the MCI group were significantly lower compared with NC group. Phase values of the right (R)-RN, bilateral DN, and bilateral PUT in the AD group were significantly lower compared with the MCI group. Phase values of the bilateral HP, DN, RN, CN, GP, PUT, and L TC in the AD group were significantly lower compared with the NC group. Serum ferritin levels in the MCI and AD groups were significantly lower compared with the NC group. Only serum iron in the AD group was positively associated with iron content in the R-HP. Brain iron deposition and body iron levels both increased in MCI and AD patients, however, excessive brain iron accumulation may have no association with body iron level. SWI was particularly effective at recognizing the presence of brain iron in the MCI and AD groups. PMID- 28990042 TI - Hydroxytyrosol contributes to cell proliferation and inhibits apoptosis in pulsed electromagnetic fields treated human umbilical vein endothelial cells in vitro. AB - A variety of pulsed electromagnetic fields (PEMFs) have been experimentally and clinically used in an effort to promote wound healing, although the mechanisms involved remain unknown. The aim of the present study was to investigate the action of a novel protocol of co-treatment with PEMFs and hydroxytyrosol (HTY) on the proliferation and differentiation potential of human umbilical vein endothelial cells (HUVECs). The HUVECs were assigned randomly into three groups: Control, PEMF-treated and PEMF + HT-treated. The intensity of the electromagnetic field used in this protocol was 2.25 mT, the frequency of the bursts was 50 Hz and the application time was 15 min. A Cell Counting kit-8 (CCK-8) assay was used to assess cell proliferation, and cell apoptosis was analyzed by TUNEL apoptosis assay kit and calcein-acetoxymethyl/propidium iodide dual-staining assay. In addition, protein and mRNA expression levels of protein kinase B (Akt), mechanistic target of rapamycin (mTOR), transforming growth factor (TGF)-beta1 and p53 were determined by western blotting and reverse transcription quantitative polymerase chain reaction assays, respectively. The CCK-8 assay demonstrated that HTY contributed to HUVEC proliferation mediated by PEMFs in a time-dependent manner. The Transwell assay and scratch wound results demonstrated that co-treatment of HTY and PEMFs could increase HUVEC migration. Furthermore, the levels of apoptotic cells were reversed by pre-incubation with HTY in the PEMF treatment group, while PEMF treatment alone had no such effect. The proteins and mRNA expression levels of Akt, mTOR, TGF-beta1 were elevated in co-treatment of HTY and PEMFs, whereas there was no effect on levels of p53. Therefore, the results indicated that combined exposure of HUVECs to PEMFs and HTY exerted protective effects in HUVECs by promoting cell proliferation and inhibiting apoptosis. In conclusion, to the best of our knowledge, the present study was the first to demonstrate the beneficial roles of HTY and PEMF combined treatment in HUVECs, which may represent an effective treatment for wound healing. PMID- 28990044 TI - MicroRNA-320 targets mitogen-activated protein kinase 1 to inhibit cell proliferation and invasion in epithelial ovarian cancer. AB - Ovarian cancer is the second most frequently occurring cancer and the most fatal gynecological malignancy of all gynecological cancers worldwide. MicroRNAs (miR) have been reported to be downregulated or upregulated in a variety of human malignancies, and involved in the formation and progression of the majority of human cancers, including epithelial ovarian cancer (EOC). miR-320 has been identified as a tumor suppressor in multiple human cancers. However, the expression levels, biological role and underlying mechanisms of miR-320 in EOC remain to be elucidated. In the present study, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to detect miR-320 expression in EOC tissues and cell lines. Following transfection with miR-320 mimics, Cell Counting Kit 8 and cell invasion assays were utilized to investigate the effects of miR-320 on EOC cell proliferation and invasion. Bioinformatic analysis, luciferase reporter assay, RT-qPCR and western blotting were used to explore the underlying mechanism of how miR-320 affects cell proliferation and invasion in EOC. Mitogen-activated protein kinase (MAPK) 1 expression and its association with the miR-320 expression level was examined in EOC tissues. The role of MAPK1 in EOC cells was additionally evaluated by using a loss-of-function assay. The results demonstrated that miR-320 was markedly downregulated in EOC tissues and cell lines. A decreased miR-320 expression was significantly correlated with the Federation of Gynecology and Obstetrics stage and lymph node metastasis of EOC patients. Additionally, reintroduction of miR-320 expression suppressed cell proliferation and invasion in EOC. Furthermore, it was verified that MAPK1 is a direct target gene of miR-320 in EOC. MAPK1 expression was markedly upregulated in EOC tissues and inversely correlated with miR-320 expression. Furthermore, silencing of MAPK1 by RNA interference inhibited cell proliferation and invasion of EOC cells. Overall, the present study demonstrated that miR-320 may act as a useful diagnostic and therapeutic target in the treatment of EOC. PMID- 28990043 TI - Tauhe genetics of juvenile idiopathic arthritis: Searching for new susceptibility loci. AB - Juvenile idiopathic arthritis (JIA) is an autoimmune disease that is characterized by persistent chronic arthritis and affected by genetic and environmental factors. Different genetic variations have been reported as risk factors for JIA. However, given that many results could not be replicated in individuals of different ancestral origin, it was assumed that heterogeneous genetic factors are involved in this disease. In the present study, we analyzed three single nucleotide polymorphisms (SNPs), namely PTPRC (rs10919563), TYK2 (rs34536443) and PRKCQ (rs4750316), which were found to be associated with JIA in previous studies. We also investigated whether the intron-4 located 27-bp VNTR of endothelial nitric oxide synthase (eNOS), is associated with risk for JIA in Greece. In total, 125 JIA patients and 221 healthy controls from northern Greece were included in the study as a sample set. Samples were then analyzed, and genotyped for the three SNPs with TaqMan primer-probe sets, using a Real-Time PCR platform (ViiATM 7 Real-Time PCR system), while eNOS VNTR polymorphism was genotyped by PCR. Statistical analysis was performed using a GraphPad Prism statistical program. The chi2 test was used to examine differences of genotype and allele frequencies between patients and controls. Statistical significance was defined by using the two-tailed P<0.05 test. Bioinformatics analysis was conducted by using BlastP, Pymol, Maestro and Desmond. In the case-control association study performed, eNOS only was found to be associated with JIA. Genotype a/a and allele 'a' were found in a higher frequency in JIA patients than in controls [p<0.0001, odds ratio (OR)=0.15, 95% confidence intervals (CI): 0.065 0.37; and p<0.0001, OR=0.34, 95% CI: 0.23-0.49, respectively]. No associations with JIA were detected for TYK2, PTPRC or PRKCQ. Aiming to investigate the structural consequences and the structure/function relationships accompanying the Pro1104 to Ala (rs34536443) mutation on TYK2 protein, bioinformatics analysis was performed. Combining three-dimensional (3D)-modeling and molecular dynamics simulations we identified changes in structural flexibility, affecting the functionality of the kinase domain of TYK2. To the best of our knowledge, this is the first time that eNOS VNTR polymorphism is associated with susceptibility to JIA, suggesting a differential role of allele 'a' in various complex diseases. The current data emphasize the importance of comparative studies in populations of a different ancestral background towards the clarification of the role of specific alleles in the development of JIA. PMID- 28990045 TI - Anti-tumor effects of bakuchiol on human gastric carcinoma cell lines are mediated through PI3K/AKT and MAPK signaling pathways. AB - Bakuchiol is extracted from Psoralea corylifolia, a member of the Leguminosae family, has been used in Indian Ayurvedic and Chinese traditional medicine, and it possesses an anticancer effect. The primary aim of the present study was to identify the molecular mechanisms underlying the anticancer effect of bakuchiol monoterpenes. Bakuchiol treatment significantly inhibited NUGC3 human gastric cancer cell viability in a concentration dependent manner. In addition, bakuchiol significantly increased the apoptotic cell population in the sub-G1 phase, and Annexin-V-fluorescein isothiocyanate/propidium iodide double staining confirmed the increase in apoptosis. Nuclear fragmentation and the formation of apoptotic organelles were promoted in bakuchiol-treated NUGC3 cells. Western blotting results indicated that bakuchiol treatment significantly decreased procaspase 3,6,8,9 and poly (ADP-ribose) polymerase (PARP) expression levels, increased cleaved caspase-3 and cleaved PARP expression levels, and increased the B cell lymphoma-2 associated X, apoptosis regulator:B cell lymphoma-extra large ratio. Bakuchiol-treated NUGC3 cells demonstrated significantly reduced phosphorylated (p-) protein kinase B (AKT) protein expression levels and elevated p extracellular signal related kinase 1/2 (ERK1/2), p-c-Jun N-terminal kinase (JNK) and p-p38. Bakuchiol-induced cell death was mitochondrial dependent, through modulation of phosphoinositide 3-kinase/AKT and mitogen-activated protein kinase signaling pathways. These findings demonstrated that bakuchiol possesses potential for treating human gastric cancer. PMID- 28990046 TI - Mechanism of the effect of saikosaponin on atherosclerosis in vitro is based on the MAPK signaling pathway. AB - The present study aimed to investigate the effects of saikosaponin on oxidized low-density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cell (HUVEC) injury and apoptosis, and examine the involvement of the mitogen activated protein kinase (MAPK) signaling pathway. The viability and apoptosis of HUVECs were detected using an MTT assay and flow cytometry. ELISA analysis was applied to measure the levels of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 cytokines. Nuclear factor (NF)-kappaB p65 nuclear translocation was observed using immunofluorescence staining. The levels of intercellular adhesion molecule 1 and vascular cell adhesion molecule-1 were detected using reverse transcription-polymerase chain reaction analysis. The phosphorylation of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), caspase-3 p38, c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK)1/2 were detected using western blot analysis. The results revealed that saikosaponin increased the viability of the HUVECs and decreased the early stage apoptotic rate of the HUVECs induced by ox-LDL. The expression levels of inflammatory cytokines in the injured vascular endothelial cells were decreased, the expression levels of adhesion molecules were reduced, the activity of superoxide dismutase was increased, and malondialdehyde content was decreased. Therefore, the inflammatory response and oxidative stress were inhibited. Simultaneously, the levels of Bcl-2 increased, the levels of Bax and caspase-3 decreased, and the nuclear translocation of NF-kappaB p65 was significantly inhibited. The protein levels of phosphorylated p38 and JNK were reduced, whereas that of ERK1/2 remained unaffected. It was concluded that the MAPK signaling pathway mediated HUVEC injury induced by ox-LDL. However, saikosaponin inhibited the HUVEC injury induced by ox-LDL through inhibiting the ERK1/2 and p38 MAPK signaling pathways, and possibly also through the JNK and p38 MAPK signaling pathway. PMID- 28990047 TI - Impact of biopersistent fibrous dusts on glycolysis, glutaminolysis and serine metabolism in A549 cells. AB - The conversion rates of different metabolic pathways summarized as a metabolic signature mirror the physiological functions and the general physiological status of a cell. The present study compared the impact of crocidolite and chrysotile asbestos, glass fibers and multi-walled carbon nanotubes (MWCN) of two different lengths (1-2 um and 5-15 um) on the conversion rates in glycolysis, glutaminolysis and serine metabolism of A549 cells. The concentration tested was 1 ug/cm2 for all fibers. A concentration of 5 ug/cm2 was additionally used for chrysotile and crocidolite, and 25 ug/cm2 for glass fibers and MWCN. With respect to the inhibitory effect on cell proliferation and the extent of metabolic alterations, the present study revealed the following ranking among the fibers tested: Chrysotile>crocidolite>glass fibers>MWCN 5-15 um>MWCN 1-2 um. For the asbestos and glass fibers this ranking correlated best with the number of fibers. It appeared that the results observed for MWCN did not match this correlation. However, electron microscopy revealed an agglomeration of MWCN. The agglomeration decreased the toxicologically relevant number of fibers by forming larger particle-like shapes and explained the smaller effects of MWCN 5-15 um and 1-2 um on cell proliferation and metabolism. PMID- 28990048 TI - Chlorogenic acid suppresses lipopolysaccharide-induced nitric oxide and interleukin-1beta expression by inhibiting JAK2/STAT3 activation in RAW264.7 cells. AB - Chlorogenic acid (CA) is a phenolic compound purified from coffee, fruits and their associated beverages, which possess various biological properties, such as antioxidant and anticarcinogenic activities. The present study evaluated the effects of CA on lipopolysaccharide (LPS)-induced inflammation in RAW264.7 cells and the associated intracellular signaling pathways using reverse transcription quantitative polymerase chain reaction, western blotting and enzyme-linked immunosorbent assays. CA pretreatment inhibited LPS-induced expression of inducible nitric oxide synthase (iNOS), nitric oxide (NO) and pro-inflammatory mediators including interleukin (IL)-6, tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-2 (MIP-2) and IL-1beta in RAW264.7 cells. In addition, phosphorylation of Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) with LPS was inhibited by CA pretreatment. CA and STAT3 inhibitor (STAT3i) pretreatment inhibited LPS-induced nuclear translocation of phosphorylated STAT3. In addition, STAT3i inhibited the LPS-induced expression of iNOS, NO and IL-1beta similar to the results of CA pretreatment. By contrast, STAT3i did not inhibit the LPS-induced increase in IL-6, TNF-alpha and MIP-2 expression. These results indicate that CA may suppress LPS-induced NO and IL 1beta expression by inhibiting JAK2/STAT3 activation in RAW264.7 cells. PMID- 28990049 TI - miRNA-34a-5p downregulation of VEGFA in endometrial stem cells contributes to the pathogenesis of endometriosis. AB - Endometrial-derived stem cells (EnSCs) serve an important role in the development of endometriosis via retrograde menstruation. Abnormal expression of miRNAs in EnSCs is involved in the etiology of endometriosis, however, the mechanisms remain unclear. The aim of the present study was to investigate the expression of miR-34a-5p and VEGFA in endometrial samples from patients with or without endometriosis, and then examine the underlying mechanism of microRNA-34a-5p regulation of VEGFA in EnSCs. Endometrial samples from patients with or without endometriosis were collected, and miR-34a-5p expression in the two groups was measured using RT-PCR. Human endometrial-derived stem cells (hEnSCs) were isolated from these endometrial samples, and hEnSCs were transfected with the miR 34a-5p mimics or control miRNAs. qPCR and western blotting were performed to assess the effects of miR-34a-5p on the expression of VEGFA in hEnSCs, and cell growth was assessed by an MTT assay. miR-34a-5p was significantly downregulated in patients with endometriosis when compared with that of those without endometriosis. VEGFA expression levels in hEnSCs with an overexpression of miR 34a-5p were significantly reduced when compared with those in the negative control (P<0.01). In addition, the upregulation of miR-34a-5p suppressed EnSCs proliferation by targeting the 3' untranslated region of VEGFA. miR-34a-5p provides a novel avenue for the understanding of the development of endometriosis, and may facilitate the development of potential therapeutics against endometriosis. PMID- 28990050 TI - Dietary n-3 polyunsaturated fatty acids ameliorate Crohn's disease in rats by modulating the expression of PPAR-gamma/NFAT. AB - Dietary n-3 polyunsaturated fatty acid (PUFA) exerts anti-inflammatory and immunoregulatory effects via downregulation of the innate and adaptive immune responses. However, the effect of dietary n-3 PUFA on experimental Crohn's Disease (CD) in rats and the underlying mechanisms are unclear. The present study aimed to investigate the effects of n-3 PUFA on CD induced by 2,4,6 trinitrobenzene sulfonic acid (TNBS) in rats, and to determine the underlying mechanisms, including the peroxisome proliferator-activated receptor (PPAR)-gamma and nuclear factor of activated T-cells (NFAT) pathway. Sprague-Dawley rats (n=90) were randomly assigned to the following groups: Control (intragastric distilled water); PUFA control (intragastric n-3 PUFA, 20 mg/kg/day); trans-fatty acid (TFA) control (intragastric TFA, 13 mg/kg/day); model (intragastric distilled water + TNBS); PUFA model (intragastric n-3 PUFA, 20 mg/kg/day + TNBS); and TFA model (intragastric TFA, 13 mg/kg/day + TNBS). The disease activity index (DAI), colon macroscopic damage index (CMDI) and tissue damage index (TDI) were evaluated. The expression of PPAR-gamma, NFAT, interleukin (IL)-4 and IL-2 mRNA in colonic tissues was determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and the serum levels of IL-6, IL-12, tumor necrosis factor-alpha and interferon-gamma were measured by ELISA. The results demonstrated that dietary n-3 PUFA markedly attenuated colonic inflammation compared with the model group, as indicated by reduced DAI, CMDI and TDI scores, amelioration in pathological evaluation and improvements in localized mucosal inflammation, as indicated by the levels of cytokines associated with local mucosal immunity. Treatment with n-3 PUFA increased the gene expression of PPAR gamma in TNBS-treated rats, and reduced the expression of NFAT, which ultimately reduced the release of IL-4 and IL-2 detected by RT-qPCR. A TFA-enriched diet was observed to increase DAI and TDI scores, aggravate pathological inflammation with epithelioid granulomas and enhance the release of proinflammatory cytokines, compared with the model group. In conclusion, the present study demonstrated that dietary n-3 PUFA may attenuate experimental CD induced by TNBS in rats by regulating the expression and activity of the PPAR-gamma/NFAT signaling pathway. These results provide a promising potential therapeutic method for the treatment of CD. PMID- 28990051 TI - Ultrasound-targeted microbubbles combined with a peptide nucleic acid binding nuclear localization signal mediate transfection of exogenous genes by improving cytoplasmic and nuclear import. AB - The development of an efficient delivery system is critical for the successful treatment of cardiovascular diseases using non-viral gene therapies. Cytoplasmic and nuclear membrane barriers reduce delivery efficiency by impeding the transfection of foreign genes. Thus, a gene delivery system capable of transporting exogenous genes may improve gene therapy. The present study used a novel strategy involving ultrasound-targeted microbubbles and peptide nucleic acid (PNA)-binding nuclear localization signals (NLS). Ultrasound-targeted microbubble destruction (UTMD) and PNA-binding NLS were used to improve the cytoplasmic and nuclear importation of the plasmid, respectively. Experiments were performed using antibody-targeted microbubbles (AT-MCB) that specifically recognize the SV40T antigen receptor expressed on the membranes of 293T cells, resulting in the localization of ultrasound microbubbles to 293T cell membranes. Furthermore, PNA containing NLS was inserted into the enhanced green fluorescent protein (EGFP)-N3 plasmid DNA (NLS-PNA-DNA), which increased nuclear localization. The nuclear import and gene expression efficiency of the AT-MCB with PNA-binding NLS were compared with AT-MCB alone or a PNA-binding NLS. The effect of the AT-MCB containing PNA-binding NLS on transfection was investigated. The ultrasound and AT-MCB delivery significantly enhanced the cytoplasmic intake of exogenous genes and maintained high cell viability. The nuclear import and gene expression of combined microbubble- and PNA-transfected cells were significantly greater compared with cells that were transfected with AT-MCB or DNA with only PNA-binding NLS. The quantity of EGFP-N3 plasmids in the nuclei was increased by >5.0-fold compared with control microbubbles (CMCB) and NLS-free plasmids. The gene expression was ~1.7-fold greater compared with NLS-free plasmids and 1.3-fold greater compared with control microbubbles. In conclusion, UTMD combined with AT-MCB and a PNA-binding NLS plasmid significantly improved transfection efficiency by increasing cytoplasmic and nuclear DNA import. This method is a promising strategy for the noninvasive and effective delivery of target genes or drugs for the treatment of cardiovascular diseases. PMID- 28990052 TI - Macrophage migration inhibitory factor knockdown inhibit viability and induce apoptosis of PVM/Ms. AB - Previous studies have suggested that macrophage migration inhibitory factor (MIF) serves an important role in hearing function; however, the underlying mechanism remains unclear. In the present study, perivascular-resident macrophage-like melanocytes (PVM/Ms) from the stria vascularis of the lateral cochlear wall in young and aged mice were isolated. The mRNA and protein expression levels of MIF were determined using reverse transcription-quantitative polymerase chain reaction analysis, and western blotting, respectively. MIF expression was knocked down in vitro and in vivo using small interfering RNA. Cell viability was determined using an MTT assay and cell apoptosis was determined using flow cytometry analysis. The hearing ability was assessed through the auditory brain stem response in vivo. The results of the current study demonstrated that the expression of MIF was significantly downregulated in aged mice compared with in young mice. Furthermore, the viability of PVM/Ms in aged mice was significantly decreased and the number of apoptotic PVM/Ms was significantly increased compared with that in young mice. Further studies demonstrated that the MIF knockdown accentuated hearing loss in young mice as compared with the scramble control group. In addition, the MIF knockdown in PVM/Ms significantly inhibited cell viability and lead to a significant increase in the apoptotic cell number as compared with the control group. In summary, these results revealed that the MIF knockdown significantly accentuates hearing loss in young mice in vivo, and significantly inhibits the viability and induces the apoptosis of PVM/Ms in vitro. Thus, the results of the present study may provide a novel potential therapeutic approach and prevention method for presbycusis. PMID- 28990054 TI - Diagnostic and prognostic value of serum interleukin-16 in patients with gastric cancer. AB - Gastric cancer (GC) is one of the major leading causes of cancer-associated mortality worldwide. Serum biomarkers have a vital role in diagnosis and prognosis of GC, and interleukin (IL)-16 may serve as a useful biomarker with prognostic value for human cancers. The current study aimed to evaluate the expression level of serum IL-16 in patients with GC, and evaluate the diagnostic and prognostic value of IL-16. ELISA was performed determine the serum IL-16 levels in patients with GC and healthy controls. Receiver operator curve analysis was performed to evaluate the diagnostic and prognostic potential value of serum IL-16 in GC diagnosis. Migration and invasion assays were performed using cells with IL-16 small interfering RNA (siRNA) knockdown. The results demonstrated that serum IL-16 levels were significantly higher in GC samples than in healthy controls, and increased serum IL-16 levels were significantly associated with tumor recurrence and poor prognosis. Knockdown of IL-16 significantly suppressed the migration and invasion of GC cells. In conclusion, the current results indicate that serum IL-16 levels may have diagnostic and prognostic value for patient with GC. PMID- 28990053 TI - P38/ERK MAPK signaling pathways are involved in the regulation of filaggrin and involucrin by IL-17. AB - Atopic dermatitis (AD) is characterized by a defective skin barrier, which increases the penetration of allergens and pathogens through the skin. The role of interleukin (IL)-17, a pro-inflammatory cytokine, in the pathogenesis of AD remains to be elucidated. The present study aimed to examine the effects of IL-17 on skin barrier proteins in the HaCaT cell line. The expression levels of filaggrin (FLG) and involucrin (IVL) were evaluated by reverse transcription quantitative polymerase chain reaction and western blot analyses of the HaCaT cells following IL-17 simulation. The role of IL-17 was further examined by using small molecule inhibitors of extracellular signal-regulated kinase (ERK) and P38. Treatment of the HaCaT cells with IL-17 resulted in reduced expression levels of FLG and IVL at the mRNA and protein levels. In addition, the gene expression levels of FLG and IVL were significantly reduced in the HaCaT cells by IL-4. Treatment with the mitogen-activated protein kinase (MAPK) inhibitors, SB203580 and PD98059, significantly inhibited the effects of IL-17 on the gene and protein expression levels of FLG and IVL. Finally, the protein levels of phosphorylated ERK and P38 were significantly increased following IL-17 stimulation. Taken together, the results revealed that IL-17 reduced the expression of FLG and IVL in HaCaT cells, and this effect involved the P38/ERK MAPK signaling pathways. PMID- 28990055 TI - Defective insulin signaling and the protective effects of dimethyldiguanide during follicular development in the ovaries of polycystic ovary syndrome. AB - It is established that the physiological effects of insulin are primarily mediated by the insulin signaling pathway. However, a defective insulin signaling is closely associated with the clinical manifestations of polycystic ovary syndrome (PCOS), which include excess androgen levels, insulin resistance and anovulation, and is involved in the pathophysiology of PCOS at the molecular level. Dimethyldiguanide (DMBG) has been widely employed to alleviate reproduction dysfunction in women with PCOS, however, the exact mechanism of this effect remains unclear. The objective of the present study was to investigate the effects of DMBG on the expression of the insulin signaling pathway in the ovaries of rats with PCOS, and to identify the potential underlying molecular mechanisms of these effects in PCOS. In the present study, a PCOS rat model was induced by letrozole, and successful establishment of the model was confirmed by examining ovarian histology and determining serum testosterone levels, by hematoxylin and eosin staining and ELISA, respectively. Subsequently, the expression of two key elements of insulin signaling, insulin receptor substrate (IRS)-2 and phosphatidylinositol 3-kinase (PI3K), was determined by immunohistochemistry and western blot analysis. The results demonstrated that IRS-2 and PI3K expression was markedly decreased in PCOS ovaries, which was rescued by DMBG treatment. These results indicate that IRS-2/PI3K signaling may be involved in the development of PCOS and the therapeutic effects of DMBG on PCOS. To further confirm the effects of DMBG on insulin signaling expression during this process, the expression of an additional two downstream proteins, phosphoinositide dependent kinase-1 (PDK-1) and the mammalian target of rapamycin (mTOR), was also investigated in the present study, and the results demonstrated that the expression of PDK-1 and mTOR was significantly reduced in PCOS ovaries and increased following DMBG treatment, further indicating that altered insulin signaling may have an important role in the development and treatment of PCOS. In conclusion, the results of the present study indicate that the reduced expression of proteins involved in insulin signaling may contribute to the development of the clinical features of PCOS, and DMBG reverses reduced expression of insulin signaling components, by a mechanism that is yet to be determined, to attenuate certain symptoms of PCOS, such as obesity. To the best of our knowledge, the present study is the first to provide data regarding the detailed changes of insulin signaling during the development and treatment of PCOS, and may provide an important reference for clinical PCOS treatment. PMID- 28990056 TI - Arctiin regulates collagen type 1alpha chain 1 mRNA expression in human dermal fibroblasts via the miR-378b-SIRT6 axis. AB - Arctiin, a lignin isolated from Arctium lappa, exhibits a variety of biological effects, including anti-viral, anti-inflammatory, and anti-proliferative actions, in mammalian cells. In a previous study, arctiin was demonstrated to induce procollagen type I synthesis and exhibited protective effects against ultraviolet B (UVB) radiation in normal human dermal fibroblasts (nHDFs). However, the underlying molecular mechanism of arctiin-mediated collagen synthesis remains unknown. In the present study, the mechanism for increased expression of collagen type 1alpha 1 chain (COL1A1) mRNA in arctiin-induced nHDFs was identified. The expression of microRNA-378b (miR-378b), downregulated by arctiin, was correlated with the expression of sirtuin-6 (SIRT6) mRNA, a regulator of COL1A1 mRNA. Furthermore, it was revealed that arctiin protected the UVB radiation-mediated decrease in COL1A1 mRNA expression, through the miR-378b/SIRT6 signaling pathway. In conclusion, these results suggest that arctiin regulates COL1A1 through the miR-378b-SIRT6 axis. PMID- 28990057 TI - ID3 may protect mice from anti-GBM glomerulonephritis by regulating the differentiation of Th17 and Treg cells. AB - Anti-glomerular basement membrane glomerulonephritis (anti-GBM GN) is an autoimmune disease that leads to severe and rapidly progressive renal injury. Inhibition of DNA-binding factor 3 (ID3) serves a key role in autoimmune diseases, such as asthma and Sjogren's syndrome, and in experimental allergic encephalitis models. However, the role of ID3 in the progression of anti-GBM GN remains unknown. In the present study, ID3 mRNA expression increased between 3- and 20-fold in the renal tissues of anti-GBM GN mice compared with the Control group, with a peak at day 14 post-induction. In addition, ID3 protein expression was upregulated from day 7 onwards. The expression of ID3 was also examined in the spleen, and was demonstrated to be increased in the spleen of nephritic mice. T helper 17 (Th17) cells and regulatory T (Treg) cells were present throughout the entire period of observation (from day 7 to day 28) in anti-GBM GN mice, which may vary at different time points, accompanied with the expression of ID3. In vitro, ID3 expression was increased when CD4+ T cells differentiated into Tregs; however, expression was lower in Th17 cells. Following treatment with ID3 small interfering RNA, RAR-related orphan receptor gammat, but not forkhead box P3, expression increased. Furthermore, increased expression of interleukin-17A was also observed when ID3 was blocked. In addition, ID3 was able to interact with transcription factor E2A. A significant increase in binding between ID3 and E2A was observed in anti-GBM GN from day 7 onwards, with a peak at day 14 in both renal tissue and spleen. In conclusion, ID3 may be involved in the differentiation of Th17 and Tregs by downregulating Th17 cells, which is probably associated with binding to E2A. The present results suggested that ID3 may offer protection against anti-GBM GN in mice. PMID- 28990059 TI - Expression of NR1 and apoptosis levels in the hippocampal cells of mice treated with MK-801. AB - The aim of the present study was to investigate the characteristics of N-methyl-D aspartate receptor R1 (NR1) expression and apoptosis in the nerve cells of the hippocampus in schizophrenia-like mice. C57BL/6 mice were randomly allocated to the following groups: i) Blank group; ii) MK-801 group; iii) MK-801+NMDA group, according to body weight. The NMDAR antagonist, MK-801 (0.6 mg/kg/d) was intraperitoneally injected daily for 14 days to induce a schizophrenia-like phenotype mouse model, and the effect of the NMDA injection via the lateral ventricle was observed. The results demonstrated that the number of NR1 positive cells in the MK-801 group increased in the CA1 and DG regions, indicating that NMDA may reverse this change. The level of damage decreased in the MK-801 treated group when compared with the blank group in the CA3 region. The protein expression of NR1 increased however, at the mRNA expression level, NR1 was lower in the MK-801 treated group when compared to the blank group; NMDA also reversed this change. In addition, early and total apoptosis detected in the hippocampal nerve cells was significantly increased in the MK-801 group when compared with the blank group, which was reversible following treatment with NMDA. These results indicated that NMDA may regulate the expression of NR1 and suppress apoptosis in hippocampal nerve cells in schizophrenia-like mice. Thus, NR1 may be a promising therapeutic target for the treatment of schizophrenia. PMID- 28990058 TI - Ginsenoside Rb1 inhibits free fatty acids-induced oxidative stress and inflammation in 3T3-L1 adipocytes. AB - Free fatty acids (FFAs) increase in visceral fat and are inferred to be one of the underlying inducers of adipose tissue inflammation. In our previous study, it was demonstrated that ginsenoside Rb1 stimulates endothelial nitric oxide synthase (eNOS) and Sirtuin 1 to protect against endothelial cell senescence. In the present study, 3T3-L1 adipocytes were exposed to 0.5 mM FFAs with or without Rb1 (10-40 uM). Monocyte chemotactic protein-1 (MCP-1) and interleukin-6 (IL-6) secretion was measured using ELISA. Tumor necrosis factor-alpha (TNF-alpha) expression and nuclear factor-kappaB (NF-kappaB) p65 phosphorylation were detected using western blot analysis. Oxidative stress was determined via measuring intracellular reactive oxygen species (ROS) and nitric oxide (NO) production. The results demonstrated that MCP-1 and IL-6 secretion, as well as TNF-alpha expression, were significantly increased following FFA treatment, which was attenuated by Rb1 in a dose-dependent manner. Furthermore, Rb1 attenuated FFA induced NF-kappaB phosphorylation, suggesting that the inhibitory effect of Rb1 on inflammatory cytokines was partially mediated through blockade of NF-kappaB phosphorylation. Further experiments demonstrated that Rb1 ameliorated FFA induced ROS generation and NO reduction through upregulation of superoxide dismutase 2 and eNOS expression. Taken together, these results demonstrate proinflammatory and pro-oxidant effects of FFA on 3T3-L1 adipocytes, which are effectively ameliorated by Rb1. Suppression of inflammatory responses and oxidative stress may be a novel mechanism for attenuating the effect of Rb1 on adipocyte dysfunction. PMID- 28990060 TI - MicroRNA expression profiling of intestinal mucosa tissue predicts multiple crucial regulatory molecules and signaling pathways for gut barrier dysfunction of AIDS patients. AB - Human immunodeficiency virus-1 (HIV-1) infection severely damages the gut associated lymphoid tissue (GALT), the immune system and the gut barrier, which leads to accelerating the disease progression for patients with acquired immune deficiency syndrome (AIDS). Dysregulation of microRNAs (miRNAs) may contribute to this process. However, few studies have investigated the importance of miRNAs in AIDS pathogenesis and progression. The whole miRNA profile of patients with HIV infection from southwest P.R. China and the mode of interaction between HIV-1 and miRNAs remains to be elucidated. Colon mucosal samples were collected from HIV+ patients and HIV- healthy individuals, miRNAs were isolated and subjected to array hybridization in the present study. A total of 476 human and virus-derived microRNAs were significantly altered in the HIV+ group when compared with the control group (P<0.05), which may be involved in the progression to AIDS. Target genes of the significantly altered miRNAs were predicted using the TargetScan, miRbase and miRanda databases and the 10 shared target genes of upregulated miRNAs and the 391 target genes of downregulated miRNAs were selected. As only 10 target genes were predicted for upregulated miRNAs, subsequent GO and KEGG pathway analyses were focused on the 391 target genes of the downregulated miRNAs. The findings of the present study identified a series of crucial pathways, including cell-extracellular matrix interaction and chemokine regulation, which indicated close affinity with CD4+ T cell activation. These pathways, involving genes such as integrin alpha5, led to a gut barrier dysfunction of patients with HIV. Important miRNAs include hsa-miRNA-32-5p, hsa miRNA-195-5p, hsa-miRNA-20b-5p, hsa-miRNA-590-5p. The expression levels of the miRNAs and their target genes were confirmed using RT-qPCR. Taking into previous observations, the findings of the present study identified the importance of miRNAs for regulating gut barrier dysfunction via multiple regulatory molecules and signaling pathways, which elucidated the underlying molecular mechanism of gut barrier dysfunction in patients with HIV. PMID- 28990061 TI - Imperatorin possesses notable anti-inflammatory activity in vitro and in vivo through inhibition of the NF-kappaB pathway. AB - Imperatorin (IMT) is a furanocoumarin from the root of Phlomis younghusbandii (Lamiaceae) with various activities. In the present study, the anti-inflammatory effects of IMT were evaluated by examining dimethylbenzene-induced ear edema, acetic acid-induced vascular permeability and by performing cotton pellet granuloma assessments in mice. In addition, the expression of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL 1beta, were detected using enzyme-linked immunosorbent assay kits in mice and using reverse transcription polymerase chain reaction analysis in RAW 264.7 cells. The expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear p65, cytosolic p65 and inhibitor of nuclear factor (NF)-kappaB (IkappaB) in RAW 264.7 cells were determined using western blot analysis. The results showed that the oral administration of IMT significantly inhibited the inflammatory reactions and reduced the release of TNF alpha, IL-6 and IL-1beta reactions and reduced and suppressed the mRNA expression of TNF-A expressionact1o, and the protein expression of iNOS and COX-2 in the RAW 264.7 cells. The results also indicated that IMT suppressed the activity of NF kappaB via upregulating p65 and IkappaB in the cytoplasm and downregulating p65 in the nucleus. In conclusion, IMT possessed notable anti-inflammatory activities in vitro and in vivo through inhibiting the NF-kappaB pathway. PMID- 28990062 TI - Regulation of M1-type and M2-type macrophage polarization in RAW264.7 cells by Galectin-9. AB - Generally considered as a potent pro-inflammatory signal, beta-galactosidelectin suppresses T cell receptor activation, can both promote and inhibit integrin mediated adhesion and is required in nuclear pre-mRNA splicing. Galectin-9 (Gal 9), a member of beta-galactoside lectin, is involved many processes of T cell mediated diseases (such as autoimmune diseases and asthma) and immunomodulation of macrophages. Macrophages are involved in the occurrence of inflammation, development and digestion and other stages. At different stages of the inflammatory response, macrophages exhibit different phenotypes, but mainly two subtypes, classically (M1) or alternatively (M2) polarization. The purpose of this work is to investigate the effect of overexpression or knockdown of Gal-9 on the macrophage polarization. Macrophage polarization was detected by flow cytometric profiling of secreted cytokines and specific surface markers expression, including nitric oxide synthase 2 (NOS2) and mannose receptor 1 (CD206). Protein and mRNA expression levels of TNF-alpha, TGF-beta, IL-6, IL-10, NF-kappaB, signal transducer and activator of transcription (Stat)1 and Stat3 were determined by ELISA, western blot analysis or qRT-PCR. Our results implied that differentiation of the mouse macrophage line RAW264.7 into M1-type and M2 type macrophages is followed by marked variations of Gal-9 expression. Furthermore, its overexpression and secretion are tightly associated with M2-type macrophages, whereas its downregulation promotes macrophages to polarize into M1 type macrophages, which confirmed by elevated CD206 and NOS2, respectively. In response to the changes of Gal-9 expression, cytokines, transcription factors and regulators, including TNF-alpha, IL-6, NF-kappaB, Stat1, TGF-beta, IL-10, and Stat3, were tightly regulated and significantly associated with classically and alternatively activated macrophages. Consistent with characteristics of M1-type macrophages, the transcriptional or translational expression levels or activity of TNF-alpha, IL-6, Stat1 and NF-kappaB were markedly increased with knockdown of Gal-9 in macrophages. By contrast, the expression levels or activity of TGF-beta, IL-10 and Stat3 were clearly elevated in macrophages with Gal-9 overexpression, which is closely related with M2-type macrophages. Specific expression and secretion patterns of cytokines, transcription factors and regulators in M1-type and M2-type macrophages contribute to better understanding the role of Gal-9 in regulation in macrophages. This study provides a new insight that Gal-9 may be a new immunomodulatory target for macrophages. PMID- 28990063 TI - Bioinformatics analysis of gene expression data for the identification of critical genes in breast invasive carcinoma. AB - Gene expression data were analyzed in order to identify critical genes in breast invasive carcinoma (BRCA). Data from 1,073 BRCA samples and 99 normal samples were analyzed, which were obtained from The Cancer Genome Atlas. Differentially expressed genes (DEGs) were identified using the significance analysis of microarrays method and a functional enrichment analysis was performed using the Database for Annotation, Visualization and Integrated Discovery. Relevant microRNAs (miRNAs), transcription factors (TFs) and associated small molecule drugs were revealed by Fisher's exact test. Furthermore, protein-protein interaction (PPI) information was downloaded from the Human Protein Reference Database. Interactions with a Pearson's correlation coefficient >0.5 were identified and PPI networks were subsequently constructed. A survival analysis was also conducted according to the Kaplan-Meier method. Initially, the 1,073 BRCA samples were clustered into seven groups, and 5,394 DEGs that were identified in >=4 groups were selected. These DEGs were involved in the cell cycle, ubiquitin-mediated proteolysis, oxidative phosphorylation and human immunodeficiency virus infection. In addition, TFs, including Sp1 transcription factor, DAN domain BMP antagonist family member 5, MYCN proto-oncogene, bHLH transcription factor and cAMP responsive element binding protein (CREB)1, were identified in the BRCA groups. Seven PPI networks were subsequently constructed and the top 10 hub genes were acquired, including RB transcriptional corepressor 1, inhibitor of nuclear factor (NF)-kappaB kinase subunit gamma, NF-kappaB subunit 2, transporter 1, ATP binding cassette subfamily B member, CREB binding protein and proteasome subunit alpha3. A significant difference in survival was observed between the two combined groups (groups-2, -4 and -5 vs. groups-1, -3, 6 and -7). In conclusion, numerous critical genes were detected in BRCA, and relevant miRNAs, TFs and small molecule drugs were identified. These findings may advance understanding regarding the pathogenesis of BRCA. PMID- 28990064 TI - Gaseous signalling molecule SO2 via Hippo-MST pathway to improve myocardial fibrosis of diabetic rats. AB - Recent studies have indicated the existence of an endogenous sulfur dioxide (SO2) generating system in the cardiovascular system. The present study aimed to discuss the function and regulatory mechanism of gaseous signal molecule SO2 in inhibiting apoptosis and endoplasmic reticulum stress (ERS) via the Hippo-MST signaling pathway to improve myocardial fibrosis of diabetic rats. A total of 40 male Sprague-Dawley rats were randomly divided into four groups (10 rats per group): Normal control group (control group), diabetic rats group [streptozotocin (STZ) group], SO2 intervention group (STZ+SO2 group) and diabetes mellitus rats treated with L-Aspartic acid beta-hydroxamate (HDX) group (HDX group). Diabetic rats models were established by intra-peritoneal injection of STZ (40 mg/kg) Following model establishment, intra-peritoneal injection of Na2SO3/NaHSO3 solution (0.54 mmol/kg) was administered in the STZ+SO2 group, and HDX solution (25 mg/kg/week) was administered in the HDX group. A total of 4 weeks later, echocardiography was performed to evaluate rats' cardiac function; Masson staining, terminal deoxynucleotidyl transferase dUTP nick end labeling staining and transmission electron microscopy examinations were performed to observe myocardial morphological changes. ELISA was employed to determine the SO2 content. Western blot analysis was performed to detect the expression of proteins associated with apoptosis, ERS and the Hippo-MST signalling pathway. Compared with the control group, the STZ group and HDX group had a disordered arrangement of myocardial cells with apparent myocardial fibrosis, and echocardiography indicated that the cardiac function was lowered, there was an obvious increase of apoptosis in myocardial tissue, the expression levels of apoptosis-associated protein B-cell lymphoma associated protein X, caspase-3 and caspase-9 were upregulated, and Bcl-2 expression was downregulated. The expression of ERS and Hippo-MST pathway-associated proteins, including CHOP, GRP94, MST1 and MST2, were significantly upregulated. By contrast, these above-mentioned changes were reversed by SO2 treatment. Compared with STZ group, the HDX group had a further increase of myocardial fibrosis and apoptosis, while there were no statistically significant differences in the expression of Bax/Bcl-2, caspase-3, caspase-9 and ERS and Hippo-MST pathway-associated proteins. The results of the present study demonstrated that the gaseous signal molecule SO2 can effectively improve the myocardial fibrosis of diabetic rats, and its mechanism may be associated with reduced apoptosis and ERS by downregulated Hippo-MST pathway. PMID- 28990065 TI - Inhibition of cardiotrophin-1 overexpression is involved in the anti-fibrotic effect of Astrogaloside IV. AB - Astragaloside IV (AsIV), one of the major active ingredients in Astragalus membranaceus, has demonstrated remarkable antifibrotic effects via its antioxidative activity. Cardiac fibrosis is an important pathological mechanism during cardiac remodelling associated with heart failure. In the present study, the mechanism underlying the antifibrotic effect of AsIV upon isoprenaline (ISO) stimulation was investigated. AsIV significantly improved cardiac fibrosis in vivo and dose-dependently inhibited ISO-induced CF proliferation in vitro. The ISO-triggered elevation in reactive oxygen species (ROS) levels was remarkably inhibited by AsIV, as well as ROS scavenger N-acetylcysteine (NAC), and not affected by cardiotrophin-1 (CT-1) knockdown. In addition, AsIV effectively reversed ISO-induced upregulation of CT-1 expression, which was blunted by pretreatment with NAC. Cardiac fibroblast (CF) proliferation and collagen Iota overexpression induced by ISO stimulation were effectively abrogated by AsIV, NAC, and CT-1 small interfering RNA transfection. Taken together, these results demonstrated that AsIV was able to effectively inhibit ISO-induced CF proliferation and collagen production through negative regulation of ROS-mediated CT-1 upregulation. PMID- 28990066 TI - Integrated microarray analysis provided novel insights to the pathogenesis of glaucoma. AB - Glaucoma is characterized as a visual field defect, which is the second most common cause of blindness. The present study performed an integrated analysis of microarray studies of glaucoma derived from Gene Expression Omnibus (GEO). Following the identification of the differentially expressed genes (DEGs) in glaucoma compared with normal control (NC) tissues, the functional annotation, glaucoma-specific protein-protein interaction (PPI) network and transcriptional regulatory network constructions were performed. The acute intraocular pressure (IOP) elevation rat models were established and reverse transcription quantitative polymerase chain reaction (RT-qPCR) was performed for DEGs expression confirmation. Three datasets were downloaded from GEO. A total of 97 DEGs, 82 upregulated and 15 downregulated were identified in glaucoma compared with NC groups with false discovery rate <0.05. Response to virus and immune response were two significantly enriched GO terms in glaucoma. Valine, leucine and isoleucine degradation was a significantly enriched pathway of DEGs in glaucoma. According to the PPI network, HDAC1, HBN, UBR4 and PDK1 were hub proteins in glaucoma. FOXD3, HNF-4 and AP-1 were the three transcription factors (TFs) derived from top 10 TFs which covered the majority of downstream DEGs in glaucoma. Based on the RT-qPCR results, the expression levels of 3 DEGs, raftlin, lipid raft linker 1 (RFTN1), PBX homeobox 1 (PBX1), HDAC1 were significantly upregulated and the expression of GEM was significantly downregulated in acute IOP elevation rat model at the first and fifth day. These four DEGs had the same expression pattern with our integrated analysis. Therefore, the current study concluded that 6 DEGs, including HEPH, SELENBP1, RFTN1, ID1, HDAC-1 and PBX1 and three TFs, including FOXD3, HNF-4 and AP-1 may be involved with the pathogenesis of glaucoma. The findings of the current study may improve diagnosis and drug design for glaucoma. PMID- 28990067 TI - Thevetiaflavone from Wikstroemia indica ameliorates PC12 cells injury induced by OGD/R via improving ROS-mediated mitochondrial dysfunction. AB - Cerebral ischemia and following reperfusion affects many people worldwide. To discover efficient therapeutic approaches, numerous natural products have been investigated. The current study investigated the protective effects of thevetiaflavone, a natural flavonoid obtained from Wikstroemia indica, and the associated mechanisms using PC12 cells induced by oxygen and glucose deprivation. As a result, thevetiaflavone improves cell viability and suppresses the leakage of lactate dehydrogenase from the cytoplasm. Further investigation of the mechanisms demonstrated that thevetiaflavone decreases overproduction of ROS and ameliorates ROS-mediated mitochondrial dysfunction, including collapse of mitochondrial membrane potential and mitochondrial permeability transition pore opening. Thevetiaflavone reduces the intracellular Ca2+ level, which is closely associated with mitochondrial function and interplays with ROS. Furthermore, thevetiaflavone inhibits apoptosis in PC12 cells through upregulating the expression of Bcl-2 and downregulating that of Bax and caspase-3 in addition to increasing the activity of caspase-3. These results further indicate the protective effects of thevetiaflavone in vivo and its application in the clinic. PMID- 28990068 TI - MACC1 facilitates chemoresistance and cancer stem cell-like properties of colon cancer cells through the PI3K/AKT signaling pathway. AB - With regards to colon cancer, resistance to 5-fluorouracil (5-FU)-based chemotherapy and cancer stem cells (CSCs) are considered important factors underlying therapy failure. Metastasis-associated colon cancer 1 (MACC1) has been associated with poor prognosis and the promotion of metastasis within several types of cancer. However, the biological behavior of MACC1 in chemoresistance and CSC-like properties remains unclear. In the present study, various methods including gene knockdown, gene overexpression, western blotting, quantitative polymerase chain reaction and MTT assay, have been adopted. According to the results of the present study, MACC1 was depleted in two colon cancer cell lines resistant to 5-FU; subsequently, CSC-like properties and 5-FU sensitivity were investigated. Within 5-FU-resistant cells, cell death was facilitated by MACC1 knockdown. Furthermore, sphere formation and the expression levels of pluripotent markers, including cluster of differentiation (CD) 44, CD133 and Nanog were reduced due to MACC1 depletion. Additionally, it was indicated that the phosphoinositide 3-kinase/protein kinase B signaling pathway may be associated with 5-FU resistance and CSC-like properties via MACC1. PMID- 28990069 TI - Knockdown of Indian hedgehog protein induces an inhibition of cell growth and differentiation in osteoblast MC3T3-E1 cells. AB - Indian hedgehog protein (Ihh) is evolutionarily conserved and serves important roles in controlling the differentiation of progenitor cells into osteoblasts. Ihh null mutant mice exhibit a failure of osteoblast development in endochondral bone. Although studies have demonstrated that Ihh signaling is a potent local factor that regulates osteoblast differentiation, the specific transcription factors that determine osteoblast differentiation remain unclear. Further studies are required to determine the precise mechanism through which Ihh regulates osteoblast differentiation. In the present study, Ihh was knocked down in osteoblast MC3T3-E1 cells using short hairpin RNA, to investigate the function of Ihh in osteoblast proliferation and differentiation and to examine the potential mechanism through which Ihh induces osteoblast apoptosis and cell cycle arrest. It was observed that the knockdown of Ihh induced a marked inhibition of cell growth and increased the apoptosis rate compared with the negative control osteoblasts. Downregulation of Ihh resulted in a cell cycle arrest at the G1 to S phase boundary in osteoblasts. In addition, the knockdown of Ihh decreased the alkaline phosphatase activity and mineral deposition of osteoblasts. The inhibitory roles of Ihh downregulation in osteoblast growth and differentiation may be associated with the transforming growth factor-beta/mothers against decapentaplegic homolog and tumor necrosis factor receptor superfamily member 11B/tumor necrosis factor ligand superfamily member 11 signaling pathways. Manipulating either Ihh expression or its signaling components may be of benefit for the treatment of skeletal diseases. PMID- 28990070 TI - Metformin accelerates wound healing in type 2 diabetic db/db mice. AB - Wound healing impairment is increasingly recognized to be a consequence of hyperglycemia-induced dysfunction of endothelial precursor cells (EPCs) in type 2 diabetes mellitus (T2DM). Metformin exhibits potential for the improvement of endothelial function and the wound healing process. However, the underlying mechanisms for the observed beneficial effects of metformin application remain to be completely understood. The present study assessed whether metformin, a widely used therapeutic drug for T2DM, may accelerate wound closure in T2DM db/db mice. Genetically hyperglycemic db/db mice were used as the T2DM model. Metformin (250 mg/kg/day; intragastric) was administered for two weeks prior to EPC collection and wound model creation in db/db mice. Wound healing was evaluated by alterations in the wound area and the number of platelet endothelial cell adhesion molecule-positive cells. The function of the isolated bone marrow derived EPCs (BM-EPCs) was assessed by a tube formation assay. The number of circulating EPCs, and the levels of intracellular nitric oxide (NO) and superoxide (O2-) were detected by flow cytometry. Thrombospondin-1 (TSP-1) expression was determined by western blot analysis. It was observed that treatment with metformin accelerated wound healing, improved angiogenesis and increased the circulating EPC number in db/db mice. In vitro, treatment with metformin reversed the impaired BM-EPC function reflected by tube formation, and significantly increased NO production while decreasing O2- levels in BM-EPCs from db/db mice. In addition, TSP-1 expression was markedly attenuated by treatment with metformin in cultured BM-EPCs. Metformin contributed to wound healing and improved angiogenesis in T2DM mice, which was, in part, associated with stimulation of NO, and inhibition of O2- and TSP-1 in EPCs from db/db mice. PMID- 28990071 TI - miR-494 inhibits cell proliferation and metastasis via targeting of CDK6 in osteosarcoma. AB - Tumorigenesis is a multistep process involving various cell growth-associated factors. Accumulated evidence indicates that the disordered regulation of microRNAs (miRNAs) contributes to tumorigenesis. However, the detailed mechanism underlying the involvement of miRNAs in oncogenesis remains to be fully elucidated. In the present study, the repressed expression of microRNA (miR)-494 was identified in 18 patients with osteosarcoma (OS) and OS cell lines, compared with corresponding controls. To determine whether deregulated miR-494 exerts tumor-suppressive effects in the development of OS, the effects of miR-494 on cell proliferation and metastasis were evaluated. It was found that the restoration of miR-494 in MG-63 and U2OS cells led to inhibited cell proliferation and attenuated migratory propensity in vitro, determined through analysis using MTT, colony formation and Transwell assays. In addition, overexpression of miR-494 markedly suppressed the tumor volume and weight in vivo. In accordance, the ectopic expression of miR-494 induced cell cycle arrest at the G1/S phase in OS cells. Bioinformatics analysis and luciferase reporter assays were performed to investigate the potential regulatory role of miR-494, the results of which indicated that miR-494 directly targeted cyclin-dependent kinase 6 (CDK6). Of note, the data obtained through reverse transcription quantitative polymerase chain reaction and western blot analyses suggested that the elevated expression of miR-494 resulted in reduced mRNA and protein expression levels of CDK6. Taken together, these findings indicated that the miR 494/CDK6 axis has a significant tumor-suppressive effect on OS, and maybe a diagnostic and therapeutic target for the treatment of OS. PMID- 28990072 TI - 2,3,5,4-tetrahydroxy diphenylethylene-2-O-glucoside inhibits the adhesion and invasion of A549 human lung cancer cells. AB - Lung cancer is considered to be a serious disease that poses a significant threat to human health. 2,3,5,4-tetrahydroxy diphenylethylene-2-O-glucoside (THSG) is a bioactive compound derived from Polygonum multiflorum Thunb. That has been demonstrated to possess antioxidative, anti-inflammatory and antitumor activities. However, little is currently known regarding the potential anticancer effects of this compound in lung cancer. Therefore, the present study aimed to investigate the effects of THSG on the adhesion and invasion of A549 human lung cancer cells in vitro, and to identify the putative mechanisms involved. Cell Counting kit-8 assay was performed to determine A549 cell viability following treatment with various doses (0, 5, 10, 25, 50, 100, 150 and 200 uM) of THSG for 12, 24 and 48 h. In addition, cell adhesion and invasion were determined following treatment of A549 cells with 0, 10, 25 or 50 uM THSG for 1, 2 or 3 h, respectively. Reverse transcription-quantitative polymerase chain reaction analysis was performed to examine the mRNA expression levels of Snail, E cadherin, vimentin, matrix metalloproteinase (MMP) 2 and MMP9 following THSG treatment for 12 h. Western blot analysis was conducted to detect the protein expression levels of Snail, E-cadherin, vimentin, MMP2 and MMP9 following THSG treatment for 24 h. Treatment with THSG (10, 25 and 50 uM) significantly suppressed the adhesion and invasion of A549 human lung cancer cells in a dose dependent manner. In addition, the mRNA and protein expression levels of adhesion and invasion-associated factors were decreased significantly in A549 cells treated with THSG. In conclusion, THSG effectively suppressed the adhesion and invasion of human lung cancer cells potentially by inhibiting the expression of adhesion and invasion-related genes. PMID- 28990073 TI - NOD receptor and TLR9 modulation in severe acute pancreatitis-induced intestinal injury. AB - Severe acute pancreatitis (SAP) has a rapid onset and may cause multiple organ dysfunction syndrome (MODS), which has high mortality. Nucleotide binding oligomerization domain (NOD) receptor and Toll-like receptor 9 (TLR9), a pattern recognition receptor in innate immunity, are involved in inflammation, immunity and pathogen recognition. The role and mechanism of the NOD receptor and TLR9 in early MODS of SAP-induced intestinal injury, however, remain unclear. Wistar rats were divided into control, SAP, TLR9 inhibitor and NOD receptor activation groups. Reverse transcription-quantitative polymerase chain reaction was used to analyze the expression of TLR9, NOD1 and NOD2 in the experimental treatment groups. Serum amylase, creatinine and alanine aminotransferase indices were measured, ELISA was used to determine the expression of tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL-1beta) and western blot analysis was used to assess nuclear factor (NF)-kappaB expression levels in intestinal tissues. Reactive oxygen species (ROS) levels and superoxide dismutase (SOD) activity were quantified by spectrometry. SAP and NOD receptor activation groups exhibited significantly elevated TLR9, NOD1, NOD2, TNF-alpha, IL-1beta and nuclear factor (NF)-kappaB levels compared with the control group. Furthermore, ROS production was increased, SOD activity was decreased and higher serum indices were exhibited, compared with the control group. The NOD receptor group presented more significant differences compared with the SAP group. The TLR9 inhibitor group exhibited opposite effects, with markedly decreased TLR9, NOD1, NOD2, TNF alpha, IL-1beta and NF-kappaB levels. The TLR9 inhibitor group also presented reduced ROS production, increased SOD activity and lower serum indexes compared to the SAP group. The present study therefore indicated that NOD receptor and TLR9 may modulate the inflammatory response and further impact upon intestinal injury of SAP, via the regulation of NF-kappaB expression and the oxidation/antioxidation balance, suggesting therapeutically targeting NOD receptor and TLR9 might be a useful approach for the treatment of severe acute pancreatitis. PMID- 28990074 TI - Puerarin inhibits beta-amyloid peptide 1-42-induced tau hyperphosphorylation via the Wnt/beta-catenin signaling pathway. AB - Excessive tau protein phosphorylation is important in the pathogenesis and early abnormal signal transduction of Alzheimer's disease. Excessive phosphorylation of microtubules is associated with tau accumulation, which induces the formation of neurofibrillary tangles in neurons, leading to synaptic damage and ultimately, neurodegeneration. The present study aimed to investigate the possible mechanism underlying the inhibitory effects of puerarin on beta-amyloid peptide (Abeta)1-42 induced tau protein hyperphosphorylation in SH-SY5Y cells. Following various treatments, the viability of SH-SY5Y cells was determined using the MTT assay, and cell morphology was observed under an inverted fluorescence microscope. Western blotting was used to detect tau phosphorylation, and the protein expression levels of glycogen synthase kinase (GSK)-3beta, phosphorylated (p)-GSK 3beta (Ser9), beta-catenin and cyclin D1, which are the key factors mediating the Wnt/beta-catenin signaling pathway in SH-SY5Y cells. The results demonstrated that puerarin reversed the Abeta1-42-induced decrease in SH-SY5Y cell viability. In addition, puerarin inhibited the degree of Abeta1-42-induced tau phosphorylation at Ser396, Ser199 and Thr231 in SH-SY5Y cells, and reduced the expression of GSK-3beta by increasing the expression of p-GSK-3beta (Ser9). Furthermore, puerarin increased the protein expression levels of beta-catenin and cyclin D1, which are key factors involved in the Wnt/beta-catenin signaling pathway. The results of the present study demonstrated that puerarin may attenuate Abeta1-42-induced tau hyperphosphorylation in SH-SY5Y cells, by inhibiting the expression of GSK-3beta and activating the Wnt/beta-catenin signaling pathway; therefore, puerarin may exert protective effects against Alzheimer's disease. PMID- 28990075 TI - Ulinastatin inhibits renal tubular epithelial apoptosis and interstitial fibrosis in rats with unilateral ureteral obstruction. AB - The effect of ulinastatin (UTI) on renal tubular epithelial apoptosis and interstitial fibrosis in rats with unilateral ureteral obstruction (UUO) was investigated. A total of 18 male Wistar rats were randomly divided into the following 3 groups: The Sham group (n=6), the UUO group (n=6), and the UTI group (n=6). In the UUO and UTI groups, the left ureter was ligated to establish a UUO model. Starting from day 1 after surgery, an intervention treatment was performed using normal saline (1 ml/kg/d) and UTI (40,000 unit/kg/d). On day 7 after surgery, 6 rats from each group were sacrificed. In the Sham group, the left ureter was only freed, not ligated; after 7 days of abdominal closure, all of the rats were sacrificed. Blood samples were collected prior to sacrificing the animals to measure the blood urea nitrogen (BUN) and serum creatinine (Scr). The incidence of renal interstitial lesions on the obstruction side was observed by hematoxylin and eosin, and Masson staining. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and immunohistochemical detection of apoptosis regulator Bax (Bax), apoptosis regulator Bcl-2 (Bcl-2) and caspase-3 were performed to observe the presence of renal tubular epithelial cell apoptosis. The UTI did not have a significant influence on the mouse BUN and Scr levels in any of the groups (P>0.05). Compared with that in the Sham group, renal tissue injury in the UUO group was significantly aggravated with renal tubular dilation, epithelial cell atrophy, renal interstitial inflammatory cell infiltration and fibrous tissue hyperplasia (P<0.01). Furthermore, the renal tubular epithelial TUNEL+ cell number and Bax and caspase-3 levels were increased, and the expression of Bcl-2 was decreased (P<0.01). Following the UTI treatment, the renal interstitial injury at the obstruction side was significantly attenuated (P<0.05), the renal tubular epithelial TUNEL+ cell number, and Bax and caspase-3 levels significantly decreased, and the expression of Bcl-2 was restored (P<0.05). UTI inhibited renal tubular epithelial apoptosis and interstitial fibrosis in UUO rats. PMID- 28990077 TI - Inhibitory effect of the anthelmintic drug pyrvinium pamoate on T315I BCR-ABL positive CML cells. AB - Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder characterized by a chromosome translocation that generates the BCR-ABL oncogene, which encodes a constitutively activated tyrosine kinase. Despite progress in controlling CML at the chronic phase by first and second generations of BCR-ABL tyrosine kinase inhibitors (TKIs), effective drugs with good safety are not available for CML patients harboring T315I BCR-ABL and those in advanced stages of CML. Therefore, there is an urgent requirement for the development of effective therapies against T315I BCR-ABL. In the present study, it was demonstrated that pyrvinium pamoate, an anthelmintic drug approved by the Food and Drug Administration had potent inhibitory effects on growth and survival in CML cells with T315I BCR-ABL. In addition, this agent was equally effective in inhibiting the Wnt/beta-catenin signaling in wild-type and T315I BCR-ABL CML cells. Thus, the clinical efficacy of pyrvinium pamoate in treating patients with CML bearing T315I BCR-ABL should be further investigated. PMID- 28990076 TI - Global transcriptome-wide analysis of the function of GDDR in acute gastric lesions. AB - Acute gastric lesions induced by stress are frequent occurrences in medical establishments. The gastric dramatic downrelated gene (GDDR) is a secreted protein, which is abundantly expressed in normal gastric epithelia and is significantly decreased in gastric cancer. In our previous study, it was found that GDDR aggravated stress-induced acute gastric lesions. However, the role of GDDR in acute gastric lesions remains to be fully elucidated. In the present study, RNA sequencing was performed in order to examine the gene expression profile regulated by GDDR in acute gastric lesions. The dataset comprised four stomach samples from wild-type (WT) mice and four stomach samples from GDDR knockout mice. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to analyze the differentially expressed genes (DEGs). Weighted correlation network analysis was used to identify clusters of highly correlated genes. Cytoscape was used to construct a protein-protein interaction network (PPI) of the DEGs. Based on the GO analysis, the upregulated DEGs were distinctly enriched in muscle contraction and response to wounding; and the downregulated DEGs were significantly enriched in the regulation of nitrogen compound metabolic process and regulation of RNA metabolic process. The results of the KEGG pathway analysis showed that the upregulated DEGs were enriched in ECM-receptor interaction and the signaling pathway of cGMP PKG, and the downregulated DEGs were enriched in the renin-angiotensin system and glycerolipid metabolism. The co-expression network revealed a group of genes, which were associated with increased wound healing in the WT mice. Significant pathways were identified through the PPI network, including negative regulation of the signaling pathway of glucocorticoid receptor, regulation of cellular stress response, and regulation of hormone secretion. In conclusion, the present study improves current understanding of the molecular mechanism underlying acute gastric lesions and may assist in the treatment of gastric lesions. PMID- 28990078 TI - Increased expression of high mobility group box protein 1 and vascular endothelial growth factor in placenta previa. AB - Placenta previa is often associated with preterm delivery, reduced birth weight, a higher frequency of placental accreta and postpartum haemorrhage, and increased likelihood of blood transfusion. The present study aimed to examine the expression of high mobility group box protein 1 (HMGB1) in the placenta of women with or without placenta previa. The study group consisted of placental tissues obtained from women with or without placenta previa. The expression levels of HMGB1 and vascular endothelial growth factor (VEGF) were evaluated in the placental tissues using reverse transcription-quantitative polymerase chain reaction, western blotting and immunohistochemistry. The mRNA expression levels of HMGB1 and VEGF were significantly increased in the placenta previa group compared with in the normal group. In addition, the placenta previa group exhibited increased HMGB1 and VEGF staining in vascular endothelial cells and trophoblasts. There were no significant differences in the expression of HMGB1 or VEGF between groups with or without placenta accreta or postpartum haemorrhage. The present study hypothesised that the increased expression of HMGB1 in the placenta may be associated with the pathogenesis of placenta previa by regulating the expression of the proangiogenic factor VEGF. PMID- 28990079 TI - Effect of miR-146a-5p on tumor growth in NSCLC using chick chorioallantoic membrane assay and bioinformatics investigation. AB - Our previous study demonstrated that the expression of miR-146a-5p was downregulated in non-small cell lung cancer (NSCLC) tissue, which affected the progression and prognosis of patients with NSCLC. Thus, the present study was conducted to investigate the functional mechanism of miR-146a-5p in tumorigenesis and angiogenesis in NSCLC. Following the construction of a H460 NSCLC cell line in which miR-146a-5p was overexpressed via lentivirus transduction, the NSCLC chick embryo chorioallantoic membrane (CAM) model was established by transplanting miR-146a-5p-overexpressing NSCLC cells into the CAM. Then, the size of the neoplasms within the CAM was measured, the vessel ratio was calculated, and the cellular morphology, metastasis and inflammation of tumor cell was observed using hematoxylin and eosin staining. The target genes of miR-146a-5p were predicted by 12 online software programs; these genes were then subjected to Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway annotations using the Database for Annotation, Visualization and Integrated Discovery 6.7 as well as constructed into a protein interaction network using protein-protein interaction from Search Tool for the Retrieval of Interacting Genes/Proteins. The xenograft tumor size and angiogenesis conditions of the miR-146a-5p-overexpressing group (volume 6.340+/-0.066 mm3, vessel ratio 9.326+/-0.083) was obviously restricted (P<0.001) when compared with the low expression group (volume 30.13+/-0.06 mm3, vessel ratio 16.94+/-0.11). In addition, marked necrosis along with inflammatory cell infiltration was observed with the HE-stained slices from the miR-146a-5p low expression group. Regarding the results of the target gene prediction, cancer and toll-like receptor signaling were the two most significant pathways represented among the target genes, while JUN, EGFR and RAC1 were the most relevant proteins among the selected potential targets of miR-146a-5p. In a CAM xenograft tumor model, overexpression of miR-146a-5p inhibited the tumorigenesis and angiogenesis of an NSCLC cell line. miR-146a-5p may act as a tumor suppressor gene in NSCLC and have moderate prognostic value in lung cancer. PMID- 28990080 TI - Rapamycin promotes osteogenesis under inflammatory conditions. AB - Chronic periodontitis, a common oral disease, usually results in irreversible bone resorption. Bone regeneration is a complex process between bone-forming activity of osteoblasts and bone-resorbing activity of osteoclasts, and still remains a challenge for physicians clinically. A previous study demonstrated that the mechanistic target of rapamycin signaling pathway is involved in osteogenic differentiation of mesenchymal stromal cells. Herein, whether rapamycin could be used to induce osteogenic differentiation of primary bone marrow-derived mesenchymal stem cells (BMSCs) in vitro and promote new bone formation in vivo were evaluated. The results demonstrated that rapamycin alone was not enough to fully induce osteoblast differentiation in vitro and enhanced bone regeneration in vivo. Interestingly, rapamycin in rapamycin plus lipopolysaccharide (LPS) treated BMSCs significantly increased the gene expression levels of Sp7 transcription factor, runt related transcription factor 2, alkaline phosphatase (ALP) and collagen I (Col I), ALP activity, and calcium nodule at different time points in vitro, indicating that osteoblast differentiation occurs by rapamycin when BMSCs are exposed to LPS simultaneously. It was also demonstrated that rapamycin in rapamycin plus LPS-treated rats promoted bone regeneration in vivo. These results suggest that rapamycin may influence osteoblast differentiation and new bone formation after LPS induces an inflammatory environment. Rapamycin may be used to treat periodontitis associated with bone loss in future clinical practice. PMID- 28990081 TI - Leber's hereditary optic neuropathy is potentially associated with a novel m.5587T>C mutation in two pedigrees. AB - Mitochondrial (mt)DNA mutations have been revealed to be associated with Leber's hereditary optic neuropathy (LHON). The present study conducted clinical, genetic and molecular evaluations of two Han Chinese families. A total of 4 (3 men and 1 female) out of 14 matrilineal relatives in the families exhibited visual impairment with variable severity and age of onset. The average age of onset of visual loss was 20.5 years old. Molecular analysis of the complete mitochondrial genome in these pedigrees demonstrated that the three primary mutations associated with LHON were not detected; however, the homoplasmic m.5587T>C mutation was identified, which was localized at the end of the mitochondrially encoded transfer (t)RNA alanine gene and may alter the tertiary structure of this tRNA. Subsequently, this structural alteration may result in tRNA metabolism failure. In addition, distinct sets of mtDNA polymorphisms belonging to haplogroup F1 were detected in both families tested. The findings of the present study suggested that the m.5587T>C mutation may be involved in the pathogenesis of visual impairment. In addition, the mtDNA variant m.15024G>A(p.C93H) in the mitochondrially encoded cytochrome B gene was detected in both families, which exhibited evolutionary conservation, indicating it may serve a potential modifying role in the development of visual impairment associated with m.5587T>C mutation in these families. Furthermore, other modifying factors, including nuclear modifier genes, and environmental and personal factors may also contribute to the development of LHON in subjects carrying this mutation. PMID- 28990083 TI - Confirmation and preliminary analysis of circRNAs potentially involved in human intervertebral disc degeneration. AB - Circular RNAs (circRNAs) are relatively recently identified noncoding RNAs that are ubiquitously expressed in human tissues and serve key functions in regulating gene expression. However, few studies have focused on human intervertebral disc degeneration (IDD) circRNAs, and the potential role of circRNAs in IDD has not been described in detail. In the present study, circRNA expression data was downloaded from the Gene Expression Omnibus database, and circRNAs in the human intervertebral disc were classified according to their length, indicating their uniform distribution of circRNAs of different lengths. Gene Ontology analysis was performed, which indicated that the differentially expressed circRNAs were mainly produced as a result of catalytic activity and from binding genes in the molecular function category, cell part genes in the cellular component category, and cellular and metabolic process genes in the biological process category. Classification analysis divided the circRNAs host genes into 16 classes; with nucleic acid binding genes ranked as the most common host gene type in IDD tissue. Pathway analysis indicated that >15 signaling pathways may serve different roles in IDD, and Wnt signaling, gonadotropin-releasing hormone receptor and integrin signaling pathways may serve important roles. Using co expression analysis, 76 differentially expressed circRNAs and host gene pairs were identified, which were divided into four groups: CircRNAs and their host genes downregulated; circRNAs downregulated and host genes upregulated; circRNAs and their host genes upregulated; and circRNAs upregulated and host genes downregulated. Finally, hsa_circ_0008305 upregulation and hsa_circ_0041946 downregulation were validated in IDD using reverse transcription-quantitative polymerase chain reaction. In conclusion, the findings of the present study may shed light on the potential roles of circRNAs in IDD and the possibility for their use in the diagnosis and clinical treatment of IDD in the future. PMID- 28990082 TI - Fluid shear stress induces osteoblast differentiation and arrests the cell cycle at the G0 phase via the ERK1/2 pathway. AB - Numerous studies have demonstrated that fluid shear stress (FSS) may promote the proliferation and differentiation of osteoblast cells. However, proliferation and differentiation are mutually exclusive processes and are unlikely to be promoted by FSS simultaneously. Cell proliferation and differentiation induced by FSS has rarely been reported. In order to provide an insight into this process, the present study investigated the effects of FSS on osteoblast-like MC3T3 cells in the G0/G1 phase, the period during which the fate of a cell is determined. The results of the present study demonstrated that FSS promoted alkaline phosphatase (ALP) activity, and the mRNA expression and protein expression of osteocalcin, collagen type I and runt-related transcription factor 2 (Runx2), while inhibiting DNA synthesis and arresting the cell cycle at the G0/G1 phase. The increase in Runx2 and ALP activity was accompanied by the activation of calcium/calmodulin dependent protein kinase type II (CaMK II) and extracellular signal-regulated kinases 1/2 (ERK1/2), which was completely abolished by treatment with KN93 and U0126, respectively. In addition, the inhibition of ERK1/2, although not CaMK II, decreased p21Cip/Kip activity, resulting in an increase in cell number and S phase re-entry. The results of the present study indicated that in the G0/G1 phase, FSS promoted osteoblast differentiation via the CaMK II and ERK1/2 signaling pathways, and blocked the cell cycle at the G0/G1 phase via the ERK1/2 pathway only. The present findings provided an increased understanding of osteoblastic mechanobiology. PMID- 28990085 TI - RhoA regulates lipopolysaccharide-induced lung cell injury via the Wnt/beta catenin pathway. AB - Ras homolog family member A (RhoA) has been reported to be involved in numerous biological processes; however, the effects of RhoA on acute lung injury (ALI) have yet to be reported. The present study aimed to explore how RhoA affects cell viability, reactive oxygen species (ROS) activity and cell apoptosis in a cell model of lipopolysaccharide (LPS)-induced ALI. An MTT assay, flow cytometry, reverse transcription-quantitative polymerase chain reaction and western blotting were used to determine the effects of RhoA on cell viability, apoptosis and ROS activity. The results demonstrated that RhoA inactivation was able to promote cell viability, and decrease apoptosis and ROS activity of LPS-treated cells. The results of western blotting indicated that RhoA activated the downstream Wnt/beta catenin signaling pathway and inhibited the expression of apoptotic factors. These findings suggested that RhoA may be involved in ALI progression and could be a novel therapeutic target for this disease. PMID- 28990084 TI - Neuroprotective effect of chondroitin sulfate on SH-SY5Y cells overexpressing wild-type or A53T mutant alpha-synuclein. AB - Accumulation of alpha-synuclein (alpha-SYN) is a common pathology for Parkinson's disease (PD). There is abundant evidence that the toxic-gain-of-function of alpha SYN's is associated with aggregation and consequent effects. To assess the potential of chondroitin sulfate (CS) in this regard, the present study investigated its neuroprotective on SH-SY5Y cells overexpressing wild-type (WT) or A53T mutant alpha-SYN. Cell viability was measured by MTT assay. Apoptosis, reactive oxygen species (ROS) and mitochondrial membrane potential were detected by flow cytometry. The protein expression levels of total alpha-SYN, phosphorylated Ser129 alpha-SYN, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax) and cytochrome-c (Cyt-c ) were analyzed by western blotting. It was observed that CS reduced the expression levels of total alpha-SYN and phosphorylated Ser129 alpha-SYN, prevented cell loss and inhibited apoptosis. The subsequent mechanism study indicated that CS inhibited ROS overproduction. CS also significantly attenuated WT and A53T mutant alpha-SYN-induced dysfunction, including decrease of mitochondrial membrane potential, decrease of Bcl-2 expression, and increase of Bax expression, release of Cyt-c from the mitochondria and activation of caspase-3 and caspase-9, which demonstrated that CS suppressed alpha-SYN-induced apoptosis possibly through mitochondria protection. These results suggested that CS protects SH-SY5Y cells overexpressing WT or A53T mutant alpha-SYN by inhibiting the expression and phosphorylation of alpha-SYN, and ROS overproduction and mitochondrial apoptosis. These results implicate CS as a potential therapeutic agent for the treatment of PD. PMID- 28990086 TI - miR-647 and miR-1914 promote cancer progression equivalently by downregulating nuclear factor IX in colorectal cancer. AB - MicroRNAs (miRNAs/miRs) have been investigated as diagnostic and prognostic biomarkers for cancer; however, the significance of miRNAs in colorectal cancer (CRC) remains to be elucidated. The aim of the present study was to determine the genetic profiles of CRC tissue, and screen for miRNAs implicated in CRC cell proliferation and migration. RNA sequencing of 10 paired specimens was performed to for screen genes that were upregulated or downregulated in CRC. miRNA expression in CRC specimens and cell lines was confirmed using qPCR analysis. The significance of indicated miRNAs in CRC cell proliferation and migration was evaluated using MTT and scratch wound-healing assays. Online computational prediction, isobaric tags for relative and absolute quantification analysis and a luciferase reporter assay were applied to determine candidate targeted genes for the miRNAs. RNA-seq data revealed miR-1914 as the most prominent miRNA in CRC specimens. qPCR analysis also suggested that the expression of miR-1914, as well as its counterpart miR-647 were elevated in CRC specimens and cell lines. Suppression of miR-647/1914 using small interfering RNAs inhibited CRC SW480 and SW620 cell proliferation, and migration. Nuclear factor I/X (NFIX) was demonstrated to be a candidate for miR-647/1914 and mediated the oncogenic activity of miR-647/1914. In all, miR-647 and miR-1914 were demonstrated to promote the proliferation and migration of CRC cells by directly targeting NFIX. Therapeutic delivery of siRNAs targeting miR-647/1914 and overexpression of NFIX may be feasible approaches for CRC treatment. PMID- 28990087 TI - SiRNA directed against NF-kappaB inhibits mononuclear macrophage cells releasing proinflammatory cytokines in vitro. AB - Acute lung injury (ALI) is a condition of acute respiratory failure, characterized by diffuse pulmonary infiltrates and severe hypoxemia. During ALI, the acute phase of inflammation induces the recruitment of activated inflammatory cells, including macrophages and lymphocytes, to the damaged lesions. Nuclear factor (NF)-kappaB is a key protein in many signal transduction pathways, over activation of which is followed by an approach of inflammation cells and release of pre-inflammation cytokines. The aim of the present study was to explore the effect of NF-kappaB P65 siRNA retroviruses on the activation of NF-kappaB signaling pathway and release of pro-inflammatory cytokines in THP-1 cells. In the present study, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to detect the NF-kappaB p65 mRNA and protein expression at different times in THP-1 cells infected by p65 siRNA retroviruses. The results revealed that p65 siRNA retroviruses could significantly inhibit the expression levels of NF-kappaB p65 mRNA and protein at different times. In addition, to further investigate the effect of p65 siRNA retroviruses on the pro-inflammatory cytokines release stimulated by LPS, the expression of IL-1beta in THP-1 cells and TNF-alpha in THP-1/M cells was also detected using RT-qPCR and ELISA. As a result, the level of released proinflammatory cytokine interleukin-1beta and tumor necrosis factor-alpha stimulated was significantly inhibited at different times infected by p65 siRNA retroviruses, while increased at different times infected by siControl retroviruses in THP-1 and THP-1/M cells stimulated by LPS. In summary, the present study demonstrated that p65 siRNA retroviruses could suppress the activation of NF-kappaB signal pathway and release of pro-inflammatory cytokines in THP-1 cells which provided a clinically plausible method to inhibit the inflammation for ALI/ARDS utilizing RNA interference technology. PMID- 28990088 TI - Identification and bioinformatics analysis of miRNAs associated with human muscle invasive bladder cancer. AB - Accumulated evidence has indicated that micro (mi)RNAs play vital roles in the occurrence and development of human muscle invasive bladder cancer (MIBC), however, little is known about the miRNAs' regulatory networks. In the present study, the authors aimed to use bioinformatics analysis to identify the key miRNAs and potential target genes, as well as studying the underlying mechanisms for MIBC. They collected several human MIBC tissues to generate a miRNA expression analysis by microarray analysis comparing with normal bladder tissues, identifying 104 differentially expressed miRNAs (102 were downregulated and 2 were upregulated) and predicted 11,884 putative target genes of the dysregulated miRNAs. To understand the function of dysregulated miRNAs in the development of MIBC, networks among miRNAs and genes, gene ontologies and pathways were built. The subsequent bioinformatics analysis indicated that the mitogen-associated protein kinase (MAPK) signaling pathway, apoptosis and pathways in cancer and the cell cycle, were significantly enriched Overall, these results provided comprehensive information on the biological function of dysregulated miRNAs in the development of MIBC. The identification of miRNAs and their putative targets may offer new diagnostic and therapeutic strategies for human muscle invasive bladder cancer. PMID- 28990089 TI - Kinin B1 receptor as a novel, prognostic progression biomarker for carotid atherosclerotic plaques. AB - Stroke caused by atherosclerosis remains a leading cause of morbidity and mortality worldwide, associated with carotid plaque rupture and inflammation progression. However, the inflammatory biomarkers which aid in predicting the future course of plaques are less detailed. The present study investigated the association between plaque vulnerable and inflammatory biomarkers using blood and plaque specimens. Carotid plaque specimens were obtained from 80 patients following stroke, 14 patients suffering from transient ischaemic attack and 17 asymptomatic patients that underwent carotid endarterectomy. To assess changes in plaque characteristics at histological levels, plaques were categorized by the time between the latest ischemic stroke and surgical intervention within 30, 30 90, 90-180 and over 180 days following stroke. Serum levels of inflammatory biomarkers interleukin (IL)-6, IL-10 and kinin B1 receptor (B1R) were measured by ELISA. Histological assessment of plaque was used to evaluate the plaque stability, progression and the inflammatory biomarker levels. Comparisons of histological characteristics demonstrated that plaques revealed an unstable phenotype following stroke within 30, 30-90 days and then remodeled into more stable plaques following stroke at 90-180 and over 180 days. By comparing the serum levels of inflammatory biomarkers, it was observed that IL-6 and B1R levels tended to decline whereas IL-10 levels increased in stroke patients from <30 days to over 180 days. Immunohistochemical analysis of IL-6, IL-10 and B1R demonstrated similar alterations in serum levels. Correlation analyses revealed that only B1R serum level was significantly correlated with histological level in patients with carotid atherosclerosis. The findings revealed that serum B1R levels may provide prognostic information and currently act as potential indicators for progression in atherosclerosis. PMID- 28990090 TI - Calcineurin/NFAT signaling pathway mediates titanium particle-induced inflammation and osteoclast formation by inhibiting RANKL and M-CSF in vitro. AB - Wear particles serve a central role in periprosthetic osteolysis, which leads to the aseptic loosening of prostheses. In the present study a lentiviral vector was constructed to silence macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor kappa-B ligand (RANKL) genes, which synergistically inhibit osteoclast formation and differentiation. To confirm the role of the calcineurin/nuclear factor of activated T cells (NFAT) pathway in osteolysis, we transduced murine macrophage/monocyte RAW264.7 cells with M-CSF-short hairpin (sh)RNA-RANKL-shRNA. Tumor necrosis factor-alpha (TNF-alpha) protein levels were evaluated using enzyme-linked immunosorbent assay. Transduced RAW264.7 cells were cultured in Transwell chambers in the presence of 0.1 mg/ml titanium particles to investigate the capacity of TNF-alpha inhibition to reduce wear debris-induced inflammation. RANKL, M-CSF, TNF-alpha, interleukin (IL)-1beta, IL-6 and NFATc1 mRNA levels were also assessed by reverse transcription-quantitative polymerase chain reaction. Osteoclastogenesis was measured by tartrate-resistant acid phosphatase (TRAP) mRNA quantification. Lentiviral-mediated double gene inhibition is known to be able to completely inhibit inflammatory osteolysis, simultaneously decreasing the number of NFATc1- and TRAP-positive cells. The present study confirmed that the combined silencing of M-CSF and RANKL genes can inhibit the osteolysis induced by the wear particles around the prosthesis. The calcineurin/NFAT pathway serves a role in the prevention of prosthesis loosening. PMID- 28990092 TI - Elevated expression of SATB1 is involved in pancreatic tumorigenesis and is associated with poor patient survival. AB - Special AT-rich sequence-binding protein 1 (SATB1) is a master chromatin organizer which has been reported to be implicated in tumor progression in breast and lung cancer. However, its functions in pancreatic tumorigenesis have yet to be elucidated. In the present study, the involvement of SATB1 in pancreatic cancer development was investigated in human BxPC-3 pancreatic adenocarcinoma cells. Short hairpin (sh)RNA was used to stably downregulate SATB1 expression, and functional assays, including cell proliferation, colony formation, soft agar and migration assays, were performed in vitro. In addition, a mouse pancreatic cancer xenograft model was created to examine the tumor-promoting properties of SATB1 in vivo. The present findings demonstrated that stable knockdown of SATB1 expression inhibited the proliferation, colony formation, anchorage-independent growth and suppressed the migratory capabilities of BxPC-3 cells in vitro. In addition, SATB1 downregulation significantly inhibited tumor growth in xenografted mice in vivo. Furthermore, SATB1 was revealed to be upregulated in human pancreatic cancer tissue samples compared with matched non-cancerous adjacent tissues, and high SATB1 expression was associated with poor patient survival. Overall, the present study demonstrated that SATB1 promoted the proliferation of pancreatic cancer cells in vitro. In addition, SATB1 expression was revealed to be upregulated in human pancreatic cancer tissues and its upregulation was associated with poor patient survival. Therefore, SATB1 may have potential as a novel prognostic biomarker and therapeutic target for the treatment of patients with pancreatic cancer. PMID- 28990091 TI - WWC1 promotes podocyte survival via stabilizing slit diaphragm protein dendrin. AB - Previous studies have indicated that glomerular podocyte injury serves a crucial role in proteinuria during the process of chronic kidney disease. The slit diaphragm of podocytes forms the final barrier to proteinuria. Dendrin, a constituent of the slit diaphragm protein complex, has been observed to relocate from the slit diaphragm to the nuclei in injured podocytes and promote podocyte apoptosis. However, the exact mechanism for nuclear relocation of dendrin remains unclear. The expression of WWC1 in podocyte injury induced by lipopolysaccharides (LPS) or adriamycin (ADR) was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blotting and the immunofluorescence assay. The role of WWC1 in podocyte apoptosis was detected by knockdown of WWC1 and flow cytometry. The mRNA and protein expression levels of apoptosis associated genes Bcl-2-associated X (Bax) and Bcl-2 were measured by RT-qPCR and western blotting. The impact of WWC1 on dendrin nucleus relocation in vitro in podocytes was further evaluated by knockdown of WWC1. Expression of WWC1 significantly decreased in injured podocytes in vitro. The loss-of-function assay indicated that knockdown of WWC1 gene in vitro promoted podocyte apoptosis, accompanied with increased levels of the pro-apoptotic protein Bax and decreased levels of the anti-apoptotic protein Bcl-2. Furthermore, the relocation of dendrin protein was significantly promoted by knockdown of the WWC1 gene. In conclusion, the study indicated that loss of WWC1 may contribute to podocyte apoptosis by inducing nuclear relocation of dendrin protein, which provided novel insight into the molecular events in podocyte apoptosis. PMID- 28990093 TI - SNPs of CD14 change the mastitis morbidity of Chinese Holstein. AB - Gram-negative (GN) bacterial infection is a main cause of bovine mastitis. The cluster of differentiation (CD) 14 gene serves an essential role in GN bacterium induced innate immune response. CD14 works as a bacterial lipopolysaccharide (LPS) receptor, combines with LPS-liposaccharide binding protein complex, and causes cellular activation. However, the effects of CD14 single nucleotide polymorphisms (SNPs) on morbidity of clinical mastitis remain unclear. In the present study, To investigate the polymorphisms of CD14 gene and its effects on cows' susceptibility to mastitis, polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) assay was used to detect SNPs of CD14 gene in 134 Chinese Holsteins. SNPs were identified in PCR products amplified with 3 sets of primers in CD14 exon 2. A total of three SNPs were located in that exon: g.528 A->C (147Ser->Arg) in allele B; g.612 A->G (175Asn->Asp) in allele D; and g.1022 A->G in allele F (synonymous mutation). The SNPs in alleles B and D affected the secondary structure of CD14. A 3-dimensional (3D) structural analysis predicted three potential protein forms with a similar structure and indicated that the changes of the above-mentioned alleles were on the concave surface of the protein. In more detail, 147 Ser->Arg induced a protein kinase C phosphorylation site to move forward, as assessed by the motif analysis. The morbidity rate of AB (mixed type g.528 A/C) and CD (mixed type g.612 A/G) was the highest among all genotypes presented in the current study, and via of tumor necrosis factor-alpha and interleukin-6 mRNA levels were upregulated in animals of this genotype compared with others. Taken together, the CD14 SNPs identified in the present study, may be closely associated with the morbidity of mastitis. PMID- 28990094 TI - Identifying dysregulated pathways in postmenopausal osteoporosis through investigation of crosstalk between pathways. AB - The present study aimed to identify potential dysregulated pathways to further reveal the molecular mechanisms of postmenopausal osteoporosis (PMOP) based on pathway-interaction network (PIN) analysis, which considers crosstalk between pathways. Protein-protein interaction (PPI) data and pathway information were derived from STRING and Reactome Pathway databases, respectively. According to the gene expression profiles, pathway data and PPI information, a PIN was constructed with each node representing a biological pathway. Principal component analysis was used to compute the pathway activity for each pathway, and the seed pathway was selected. Subsequently, dysregulated pathways were extracted from the PIN based on the seed pathway and the increased classification accuracy, which was measured using the area under the curve (AUC) index according to 5-fold cross validation. A PIN comprising 2,725 interactions was constructed, which was used to detect dysregulated pathways. Notably, the 'mitotic prometaphase' pathway was selected and defined as a seed pathway. Starting with the seed pathway, network based analysis successfully identified one pathway set for PMOP comprising eight dysregulated pathways (such as mitotic prometaphase, resolution of sister chromatid cohesion, mRNA splicing and mRNA splicing-major) with an AUC score of 0.85, which may provide potential biomarkers for targeted therapy for PMOP. PMID- 28990095 TI - Kangfuxin promotes apoptosis of gastric cancer cells through activating ER-stress and autophagy. AB - Gastric cancer is a leading cause of cancer-associated mortality worldwide. In studies on the mechanisms of antigastric cancer drugs, autophagy and endoplasmic reticulum (ER) stress have been demonstrated to serve an active role in gastric cancer. The organic extract of Periplaneta americana (also termed American Cockroach), which is named Kangfuxin (KFX) in China, has been used clinically as a traditional Chinese medicine against disorders, including stomach bleeding, gastric ulcers, tuberculosis, burns and trauma. However, the role of KFX and its mechanism in gastric cancer remains to be elucidated. The present study aimed to determine the effects of KFX in vitro against cultured the human carcinoma SGC 7901 cell line, and to explore the potential mechanism of the anticancer effects of KFX in gastric cancer. SGC-7901 cells were treated with different concentrations of KFX for varying amounts of time. As a result, KFX treatment decreased the ratio of apoptosis regulators Bcl-2/Bax, activated ER stress and induced significant apoptosis in SGC-7901 cells. Furthermore, KFX was able to restore the ER stress activation blocked by 4-phenylbutyrate. In addition, KFX activated autophagy in SGC-7901 cells. These results demonstrated that ER stress, autophagy and the apoptosis-inducing effects of KFX in SGC-7901 cells may achieve promising anticancer effects in numerous other types of cancer. In particular, ER stress may serve an essential role in KFX-induced anticancer effects on gastric carcinoma and a secondary role in autophagy. PMID- 28990096 TI - High incidence of coding gene mutations in mitochondrial DNA in esophageal cancer. AB - The aim of the present study was to detect mutations in the coding genes of mitochondrial DNA (mtDNA) in three esophageal cancer cell lines and in tumor tissues obtained from 30 patients with esophageal cancer, to investigate the relationship between protein- and RNA-coding gene mutations and esophageal cancer. mtDNA was extracted and the coding genes were sequenced and analyzed by comparing the sequencing results with the complete mitochondrial genome of Homo sapiens. The results revealed 39 mutations in the three esophageal cancer cell lines; the genes with the highest mutation frequencies included mitochondrially encoded cytochrome B (MT-CYTB), NADH dehydrogenase 5 (MT-ND5) and MT-ND4 gene. A total of 216 mutations were identified in the 30 esophageal cancer tissues, including 182 protein-coding mutations, of which MT-CYTB and MT-ND5 genes exhibited higher mutation frequencies. The results of the present study indicated that mutations in the coding genes of mtDNA in esophageal cancer cells may be related to the occurrence of esophageal cancer. PMID- 28990097 TI - Fructose-1,6-bisphosphatase-1 decrease may promote carcinogenesis and chemoresistance in cervical cancer. AB - Fructose-1,6-bisphosphatase-1 (FBP1), a gluconeogenesis rate-limiting enzyme expressed in various tissues, is important in the carcinogenesis of various cancers. To evaluate the association of FBP1 expression and carcinogenesis and chemoresistance in cervical cancer, the present study analyzed 140 patients of squamous cell carcinoma of cervical cancer (CSCC) who had adjuvant concurrent chemoradiation therapy following radical surgery. By detecting FBP1 protein expression in paraffin-embedded tumor tissues through immunohistochemistry, it was observed that 50% of the cases had a low expression of FBP1, which was associated with a shorter overall survival time (P=0.011). In addition, FBP1 mRNA level was downregulated in tumor tissues, compared with cervical normal tissues. Among the tumor-associated prognostic factors, loss of FBP1 expression (chi2 test, P=0.025) was significantly associated with the tumor recurrence and greater tumor stage of cervical cancer patients (2-test, P<0.0001). In 3-(4,5) dimethylthiahiazo(-z-y1)-3,5-diphenytetrazoliumromide (MTT) assay of primary tumor cells, the median in vitro inhibition rate of cisplatin, carboplatin, nedaplatin, and oxaliplatin was 62, 47, 58 and 52%, respectively. Although there was no significant association between FBP1 expression and in vitro tumor inhibition rates of primary tumor cells, overexpression of FBP1 markedly suppressed carcinogenesis and restored the chemosensitivity to cisplatin in cervical cancer cell lines of HeLa and CaSki. Overall, decreased levels of FBP1 may be used as a predictor for poor prognosis of cervical cancer patients, however the mechanism requires further investigation. PMID- 28990098 TI - Anti-inflammatory effect of Amomum xanthioides in a mouse atopic dermatitis model. AB - Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disorder. The present study investigated the effects of Amomum xanthioides extract (AXE) on AD like skin inflammation using a Dermatophagoides farinae extract (DFE) and 2,4 dinitrochlorobenzene (DNCB)-induced mouse AD model. Hematoxylin and eosin staining results demonstrated that repeated DFE/DNCB exposure markedly increased the thickening of the dermis and epidermis, in addition to the infiltration of eosinophils and mast cells. However, oral administration of AXE reduced these histopathological alterations in a dose-dependent manner. Elevated serum histamine, total and DFE-specific immunoglobulin E (IgE), and IgG2a were also decreased by treatment with AXE. In addition, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) results demonstrated that the mRNA expression of tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-4, IL-13, IL-31 and IL-17A was reduced in ear skin following AXE administration in AD mice. Fluorescence-activated cell sorting demonstrated that the population of CD4+/IL-4+, CD4+/IFN-gamma+ and CD4+/IL-17A+ cells in draining lymph nodes was also significantly decreased in AXE-treated mice compared with AD mice without AXE treatment. Furthermore, keratinocytes that were stimulated with TNF-alpha and IFN-gamma exhibited increased gene expression of pro-inflammatory cytokines and chemokines, including TNF-alpha, IL-1beta, IL-6, IL-8, C-C motif chemokine ligand (CCL)17 and CCL22, as determined by RT-qPCR. However, upregulation of these genes was reduced by AXE pretreatment. Based on these results, we hypothesize that AXE may be useful in the treatment of allergic skin inflammation, particularly AD. PMID- 28990099 TI - Genome-wide analysis and prediction of functional long noncoding RNAs in osteoblast differentiation under simulated microgravity. AB - Long noncoding RNAs (lncRNAs) have been regarded as important regulators in numerous biological processes during cell development. However, the holistic lncRNA expression pattern and potential functions during osteoblast differentiation under simulated microgravity remain unknown. In the present study, a high throughput microarray assay was performed to detect lncRNA and mRNA expression profiles during MC3TC-E1 pre-osteoblast cell osteo-differentiation under simulated microgravity. The expression of 857 lncRNAs and 2,264 mRNAs was signi-ficantly altered when MC3T3-E1 cells were exposed to simulated microgravity. A relatively consistent distribution pattern on the chromosome and a co-expression network were observed between the differentially-expressed lncRNAs and mRNAs. Genomic context analysis further identified 132 differentially expressed lncRNAs and nearby coding gene pairs. Subsequently, 3 lncRNAs were screened out for their possible function in osteoblast differentiation, based on their co-expression association and potential cis-acting regulatory pattern with the deregulated mRNAs. The present study aimed to provide a comprehensive understanding of and a foundation for future studies into lncRNA function in mechanical signal-mediated osteoblast differentiation. PMID- 28990100 TI - Low molecular weight heparin may benefit nephrotic remission in steroid-sensitive nephrotic syndrome via inhibiting elastase. AB - Low molecular weight heparin (LMWH) has a structure similar to heparan sulfate, which exerts anti-inflammatory effects via inhibiting elastase (Ela) activity. Release of Ela along the glomerular capillary wall may induce glomerular injury and proteinuria. The present study aimed to investigate the influence of LMWH on steroid-sensitive nephrotic syndrome (SSNS) and the potential underlying mechanism. A total of 40 SSNS patients and 20 healthy controls were recruited. SSNS patients were treated with LMWH and prednisone simultaneously (LMWH+pred group) or with prednisone alone (pred group). Proteinuria, urinary glycosaminoglycans (GAGs), serum Ela and urinary creatinine levels were measured. The nephrotic period of SSNS was 15.93+/-5.78 days. The nephrotic period of SSNS in LMWH+pred group was significantly reduced compared with the pred group (14.13+/-4.56 vs. 18.63+/-6.49 days; P<0.05). At the follow-up of the SSNS patients, there was no statistically significant difference in number of relapses between the LMWH+pred and pred groups. Proteinuria (2.51+/-0.97 g/24 h), urinary GAG levels (4.92+/-0.87 mg/mmol creatinine) and serum Ela levels (77.64+/-10.99 ng/l) were significantly greater in the nephrotic period of SSNS compared with the remission period (0.107+/-0.026 g/24 h, 1.53+/-0.27 mg/mmol Cr and 41.92+/ 7.81 ng/l, respectively) and the healthy control group (0.098+/-0.027 g/24 h, 1.40+/-0.26 mg/mmol creatinine and 38.43+/-9.83 ng/l, respectively; P<0.05). During the remission period, urinary GAG and serum Ela levels in the LMWH+pred group were significantly reduced compared with the pred group (P<0.05), whereas proteinuria did not differ between these groups (P>0.05). Positive correlations were revealed between urinary GAG excretion and proteinuria (r=0.877; P<0.05), proteinuria and serum Ela levels (r=0.844; P<0.05) and serum Ela levels and urinary GAG excretion (r=0.881; P<0.05). The results of the present study indicated that elevated serum Ela levels may induce proteinuria by degrading GAGs in the glomerular basement membrane in children with SSNS. LMWH may benefit nephrotic remission of SSNS via inhibiting Ela. PMID- 28990101 TI - Exogenous peripheral blood mononuclear cells affect the healing process of deep degree burns. AB - The regenerative repair of deep-degree (second degree) burned skin remains a notable challenge in the treatment of burn injury, despite improvements being made with regards to treatment modality and the emergence of novel therapies. Fetal skin constitutes an attractive target for investigating scarless healing of burned skin. To investigate the inflammatory response during scarless healing of burned fetal skin, the present study developed a nude mouse model, which was implanted with normal human fetal skin and burned fetal skin. Subsequently, human peripheral blood mononuclear cells (PBMCs) were used to treat the nude mouse model carrying the burned fetal skin. The expression levels of matrix metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinases (TIMP)-1 were investigated during this process. In the present study, fetal skin was subcutaneously implanted into the nude mice to establish the murine model. Hematoxylin and eosin staining was used to detect alterations in the skin during the development of fetal skin and during the healing process of deep-degree burned fetal skin. The expression levels of MMP-9 and TIMP-1 were determined using immunochemical staining, and their staining intensity was evaluated by mean optical density. The results demonstrated that fetal skin subcutaneously implanted into the dorsal skin flap of nude mice developed similarly to the normal growth process in the womb. In addition, the scarless healing process was clearly observed in the mice carrying the burned fetal skin. A total of 2 weeks was required to complete scarless healing. Following treatment with PBMCs, the burned fetal skin generated inflammatory factors and enhanced the inflammatory response, which consequently resulted in a reduction in the speed of healing and in the formation of scars. Therefore, exogenous PBMCs may alter the lowered immune response environment, which is required for scarless healing, resulting in scar formation. In conclusion, the present study indicated that the involvement of inflammatory cells is important during the healing process of deep-degree burned skin, and MMP-9 and TIMP-1 may serve important roles in the process of scar formation. PMID- 28990102 TI - Role of artesunate in TGF-beta1-induced renal tubular epithelial-mesenchymal transdifferentiation in NRK-52E cells. AB - The implications of epithelial-mesenchymal transdifferentiation (EMT) have extended beyond the confines of renal fibrosis to renal tubulointerstitial fibrosis. It has been proposed that EMT may be one of the mechanisms involved in the pathogenesis of renal fibrosis. However, the underlying mechanisms remain unknown. Transforming growth factor (TGF)-beta1 is considered to be an important cytokine which regulates the transdifferentiation of tubular epithelial cells into myofibroblasts in renal tubulointerstitial fibrosis. In the present study, normal rat kidney tubular epithelial cells (NRK-52E) were treated for 48 h with TGF-beta1 (5 ng/ml) and different concentrations of artesunate (ART; 0.01, 0.1 and 1 ug/ml). Western blotting, reverse transcription-semi quantitative polymerase chain reaction analysis and immunofluorescence staining were used to evaluate the expression of bone morphogenetic protein (BMP)-7, uterine sensitization-associated gene (USAG)-1, E-cadherin, alpha-smooth muscle actin (alpha-SMA) and extracellular matrix collagen type I (Col I) mRNA. ART was able to attenuate renal injury in a unilateral ureteral obstruction model. However, its anti-fibrotic effect remains to be elucidated. In the present study, it was observed that ART was able to ameliorate the TGF-beta1-induced alterations in cellular morphology. In addition, ART inhibited the TGF-beta1-induced USAG-1 increase and the decrease in BMP-7. Treatment with ART markedly attenuated the TGF-beta1-induced upregulation of alpha-SMA and downregulation of E-cadherin. Additionally, ART was able to significantly attenuate the deposition of interstitial collagens, including Col I. The results of the present study further verified the therapeutic efficacy of ART in TGF-beta1-induced renal interstitial fibrosis. These findings indicated that ART may hold the potential to prevent chronic kidney diseases via the suppression of USAG-1 expression or by increasing BMP-7 expression. PMID- 28990103 TI - Silver nanoparticles coupled to anti-EGFR antibodies sensitize nasopharyngeal carcinoma cells to irradiation. AB - Radiotherapy is the major form of treatment for head and neck carcinoma, a malignant tumour of epithelial origin. The identification of agents, which can be co-administered in order to sensitize these tumours to radiotherapy, has become a major focus of investigations. In the present study, a novel 20 nm nanocomposite, Ag/C225, was constructed, which consisted of silver nanoparticles (AgNPs) conjugated to an epidermal growth factor receptor-specific antibody (C225). Physical characterization demonstrated that the Ag/C225 nanoparticles were spherical and dispersed well in water. Enzyme-linked immunosorbent assays showed that the activity of C225 was preserved in the Ag/C225 nanoparticles. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide analysis revealed that AgNPs and Ag/C225 inhibited the proliferation of nasopharyngeal carcinoma epithelial (CNE) cells in a dose- and time-dependent manner. Flow cytometry revealed that AgNPs and Ag/C225 induced the apoptosis of CNEs, and abrogated G2 arrest; the latter effect was more marked with Ag/C225 than with AgNPs. Clonogenic assays indicated that AgNPs and Ag/C225 increased the sensitivity of CNEs to irradiation. The sensitizer enhancement ratios were 1.610+/-0.012 and 1.405+/-0.033 Gy for AgNPs and Ag/C225, respectively. Western blot analysis revealed that combining X-ray irradiation with either AgNPs or Ag/C225 reduced the expression levels of DNA damage/repair proteins Ku-70, Ku-80 and Rad51; Ag/C225 was also more effective than AgNPs in this context. These results indicated that AgNPs and Ag/C225 effectively enhanced CNE cell radiosensitivity in vitro. Therefore, these potent agents may be considered for use as radiosensitizers during the treatment of human nasopharyngeal carcinoma. PMID- 28990104 TI - Antiangiogenic properties of caudatin in vitro and in vivo by suppression of VEGF VEGFR2-AKT/FAK signal axis. AB - Tumor angiogenesis provides essential nutrients and oxygen to the tumor microenvironment, which is important in tumor growth, progression and metastasis. Inhibition of tumor angiogenesis represents one of the most promising strategies in tumor therapy. The authors previously demonstrated that caudatin, one species of C-21 steroidal from Cynanchum auriculatum (C. auriculatum), effectively inhibits human glioma growth in vitro and in vivo through triggering cell cycle arrest and apoptosis. However, little information regarding the antiangiogenic properties of caudatin in human glioma is available. Based on the author's previous study, the antiangiogenic effect of caudatin against human glioma was explored, and the underlying mechanism was investigated. The results suggested that caudatin treatment significantly inhibited HUVEC human umbilical vein endothelial cell proliferation, blocked the HUVECs migration, invasion and capillary-like tube formation by disturbing the vascular endothelial growth factor (VEGF)-VEGFR2-protein kinase B (AKT)/focal adhesion kinase (FAK) signal axis. Notably, caudatin treatment abolished the glioma cell growth by suppression of the in vivo angiogenesis, which involved FAK and AKT dephosphorylation and inhibition of VEGF expression. The findings validated the antiangiogenic potential of caudatin in hunting human glioma. PMID- 28990105 TI - MicroRNA-24-2 is associated with cell proliferation, invasion, migration and apoptosis in renal cell carcinoma. AB - Micro (mi)RNAs are involved in multiple cellular processes, and alterations in miRNA expression have been demonstrated to lead to tumorigenesis. Previous microarray analysis revealed that miRNA (miR)-24 was downregulated in renal cell carcinoma (RCC). Additionally, miR-24 has been identified as an oncogene and tumor suppressor in various cancers. The present study assessed the expression levels of two stem-loops of miR-24, miR-24-1 and miR-24-2, in RCC tissues and paired healthy tissues by reverse transcription-quantitative polymerase chain reaction. The results revealed that miR-24-2 was upregulated in RCC tissues and ACHN, 786-O and 769P cell lines compared with healthy tissues and HEK-293T cells, respectively, whereas miR-24-1 was almost absent in RCC and healthy kidney tissues. To investigate the role of miR-24-2 in RCC, a synthesized miR-24-2 mimic, negative control (NC), inhibitor or inhibitor NC was transfected into 786 O and ACHN RCC cells, and cell proliferation, mobility and apoptosis assays were performed. The results of the present study revealed that miR-24-2 was associated with cell proliferation, migration, invasion and apoptosis, thus demonstrating that miR-24-2 may serve a role as an oncogene in RCC. Further studies are required to investigate the signaling pathways of miR-24-2, and the potential of miR-24-2 as a therapeutic target or biomarker for the early detection of RCC. PMID- 28990106 TI - Identification of key genes for diabetic kidney disease using biological informatics methods. AB - Diabetic kidney disease (DKD) is a common complication of diabetes, which is characterized by albuminuria, impaired glomerular filtration rate or a combination of the two. The aim of the present study was to identify the potential key genes involved in DKD progression and to subsequently investigate the underlying mechanism involved in DKD development. The array data of GSE30528 including 9 DKD and 13 control samples was downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) in DKD glomerular and tubular kidney biopsy tissues were compared with normal tissues, and were analyzed using the limma package. Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed for DEGs using the GO Function software in Bioconductor. The protein protein interaction (PPI) network was then constructed using Cytoscape software. A total of 426 genes (115 up- and 311 downregulated) were differentially expressed between the DKD and normal tissue samples. The PPI network was constructed with 184 nodes and 335 edges. Vascular endothelial growth factor A (VEGFA), alpha-actinin-4 (ACTN4), proto-oncogene, Src family tyrosine kinase (FYN), collagen, type 1, alpha2 (COL1A2) and insulin-like growth factor 1 (IGF1) were hub proteins. Major histocompatibility complex, class II, DP alpha1 (HLA DPA1) was the common gene enriched in the rheumatoid arthritis and systemic lupus erythematosus pathways, and the immune response was a GO term enriched in module A. VEGFA, ACTN4, FYN, COL1A2, IGF1 and HLA-DPA1 may be potential key genes associated with the progression of DKD, and immune mechanisms may serve a part in DKD development. PMID- 28990107 TI - Estradiol-enhanced osteogenesis of rat bone marrow stromal cells is associated with the JNK pathway. AB - Bone marrow stromal cells (BMSCs) can differentiate into osteoblasts. The present study investigated the osteogenic effects of estradiol, as well as the role of the c-Jun N-terminal kinase (JNK) signaling pathway in promoting estradiol enhanced osteogenesis of rat (r)BMSCs. rBMSCs were treated for 7 days with or without estradiol and further treated with or without the JNK-specific inhibitor SP600125. The role of estrogen during rBMSC osteogenesis was evaluated by alkaline phosphatase activity and mineralized nodule formation using the Gomori method and Alizarin red S staining, respectively. Subsequently, the mRNA expression levels of transforming growth factor-beta1 (TGF-beta1) and core binding factor alpha1 (Cbfalpha1) were evaluated by reverse transcription quantitative polymerase chain reaction, and TGF-beta1, Cbfalpha1 and phosphorylated (p)-JNK protein expression was detected by western blotting. All groups treated with SP600125 expressed low levels of TGF-beta1 and Cbfalpha1 mRNA and protein, and low p-JNK protein expression. Compared with the control cells, rBMSCs cultured with estradiol exhibited a significant upregulation in the expression levels of osteogenic genes and proteins. The present study demonstrated that estradiol enhanced osteogenic differentiation of rBMSCs and that the JNK signaling pathway was involved in this process, providing insights into the molecular mechanisms involved in rBMSC osteogenesis upon estradiol stimulation. PMID- 28990108 TI - The effect of anagliptin on intimal hyperplasia of rat carotid artery after balloon injury. AB - The present study evaluated the effect of anagliptin on intimal hyperplasia following carotid artery injury in Sprague-Dawley rats. Sprague-Dawley rats weighing 280-300 g were injured using a 2F Fogarty balloon embolectomy catheter. The rats were divided into injury-(saline) and anagliptin-(10 mg/kg/day) treated groups. vascular injuries were induced in the left carotid artery, followed by evaluation of neointima formation at 28 days. The right and left carotid arteries were harvested and evaluated with histological evaluation, and the plasma activity of glucagon-like peptide 1 receptor (GLP-1), stromal cell-derived factor (SDF)-1alpha, interleukin (IL)-6, IL-1beta and tumor necrosis factor (TNF)-alpha were detected by ELISA analysis. Treatment with anagliptin decreased balloon injury-induced neointima formation, compared with the injury group (P<0.01). Body weight and food consumption did not alter following treatment with anagliptin. Anagliptin caused an increase in the serum active GLP-1 concentration, compared with the injury group. In addition, serum SDF-1alpha was significantly decreased by treatment with anagliptin (P<0.001). Anagliptin altered the serum activity of IL-6, IL-1beta and TNF-alpha (P<0.01). The results of the present study demonstrated that anagliptin appeared to attenuate neointimal formation by inhibiting inflammatory cytokines and chemokines following balloon injury, and that treatment with a dipeptidyl peptidase 4 inhibitor may be useful for future preclinical studies and potentially for the inhibition of thrombosis formation following percutaneous coronary intervention. PMID- 28990111 TI - MicroRNA-720 inhibits pancreatic cancer cell proliferation and invasion by directly targeting cyclin D1. AB - Pancreatic cancer is the fourth leading cause of cancer-associated deaths in Western countries, and ranks sixth among cancer-associated diseases, with the highest mortality rate in China. Deregulation of micro (miR) RNA may contribute to the occurrence and progression of numerous cancers, including pancreatic cancer. In particular, deregulation of microRNA-720 (miR-720) has been reported in various types of human cancer. However, the expression and biological role of miR-720 in pancreatic cancer remains to be elucidated. The present study aimed to investigate the expression and functional role of miR-720 in pancreatic cancer and determine the underlying regulatory mechanism. The results demonstrated that miR-720 was expressed at low levels in pancreatic cancer tissue samples and cell lines. Upregulating miR-720 suppressed pancreatic cancer cell proliferation and invasion in vitro. Additionally, cyclin D1 (CCND1) was identified as the direct target gene of miR-720 in pancreatic cancer. Furthermore, CCND1 was significantly upregulated in pancreatic cancer tissues and inversely correlated with miR-720 expression. Furthermore, CCND1 re-expression partially abrogated the inhibitory effects of miR-720 on pancreatic cancer cells. Overall, miR-720 may act as a tumor suppressor by directly targeting CCND1 in pancreatic cancer. PMID- 28990109 TI - miR-342-5p promotes Zmpste24-deficient mouse embryonic fibroblasts proliferation by suppressing GAS2. AB - Cellular senescence is an irreversible growth arrest of cells that maintain their metabolic activities. Premature senescence can be induced by different stress factors and occurs in mouse embryonic fibroblasts (MEFs) derived from Zmpste24 metalloproteinase-deficient mice, a progeria mouse model of Hutchinson-Gilford Progeria Syndrome. Previous studies have shown that miR-342-5p, an intronic microRNA (miRNA/miR) reportedly involved in ageing associated diseases, is downregulated in Zmpste24-/- MEFs. However, whether miR-342-5p is associated with the premature senescence phenotype of Zmpste24-/- MEFs remains unclear. Thus, the present study investigated the effects of miR-342-5p on cellular senescence and cell proliferation in Zmpste24-/- MEFs. The results showed that miR-342-5p overexpression ameliorated the cellular senescence phenotype to a certain extent, promoted cell proliferation and increased the G2+M cell cycle phase in Zmpste24-/ MEFs. Nonetheless, it was difficult to observe the opposite cell phenotypes in wild-type (WT) MEFs transfected with the miR-342-5p inhibitor. Growth-arrest specific 2 (GAS2) was identified as a target gene of miR-342-5p in Zmpste24-/- MEFs. In addition, miR-342-5p was identified to be downregulated in WT MEFs during replicative senescence, while Gas2 was upregulated. Taken together, these findings suggest that downregulated miR-342-5p is involved in regulating cell proliferation and cell cycles in Zmpste24-/- MEFs by suppressing GAS2 in vitro. PMID- 28990110 TI - Effects of butylphthalide on cognitive decline in diabetic rats. AB - Butylphthalide, a component extracted from seeds of Chinese celery, is an effective neuroprotective agent used for the treatment of ischemic stroke and dementia. Diabetes may cause central nervous system damage, and diabetes is closely associated with dementia. The aim of the present study was to investigate the effects of butylphthalide on cognitive impairment in a streptozotocin-induced diabetic rat model, and the underlying mechanisms of action. A total of 30 healthy male Sprague Dawley rats were randomly divided into the following 2 groups: Normal control (NC; n=10) and diabetes model (DM) groups (n=20). Diabetes was induced in rats in the DM group by intraperitoneal injection of streptozotocin, and these rats were further subdivided into the following 2 groups: Diabetic control (n=10) and butylphthalide-treated groups (n=10). Following 8 consecutive weeks of treatment, a Morris water maze test was performed and the levels of blood fasting plasma glucose (FPG), superoxide dismutase (SOD), malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF alpha), interleukin (IL)-1beta, and IL-6 inflammatory cytokines in the hippocampus were measured. FPG levels were significantly decreased in the butylphthalide-treated group when compared with the DM group. In addition, cognitive deficits in diabetic rats were improved following butylphthalide treatment. Furthermore, butylphthalide significantly increased the level of SOD, reduced MDA levels, and reduced TNF-alpha, IL-1beta, and IL-6 levels in the hippocampus when compared with the DM group. The results of the present study suggest that butylphthalide may be an effective neuroprotective agent to improve cognitive dysfunction during diabetes. PMID- 28990112 TI - A novel compound heterozygous mutation of SLC26A4 in two Chinese families with nonsyndromic hearing loss and enlarged vestibular aqueducts. AB - Enlarged vestibular aqueduct (EVA)-associated hearing loss is frequently detected in individuals carrying the SLC26A4 mutation in the Chinese population. The present study aimed to identify the causative SLC26A4 coding mutations in a patient group with nonsyndromic hearing loss (NSHL) and EVA. Genomic DNA was extracted from blood samples obtained from 52 NSHL patients with EVA and from 60 normal controls. The mutation analysis for 20 coding exons of SLC26A4 was performed by direct sequencing. The results of the mutational analysis showed that there were two probands from two separate families suffering from bilateral sensorineural hearing loss with EVA, carrying the same novel compound heterozygous mutation of SLC26A4 (c.1644_1645insA and c.2168A>G). Other members of the two families had heterozygous mono-allelic mutations with normal hearing. However, neither of these mutations were detected in the 60 normal controls. These results are the first, to the best of our knowledge, to link the compound heterozygote mutation, c.1644_1645insA and c.2168A>G, in the SLC26A4 gene to NSHL patients with EVA. The two mutations identified in the present study were located in the anti-sigma factor antagonist domain, the core region for plasma membrane targeting of anion transporters, which suggested that the reduced or complete loss of SLC26A4 function was the direct cause of hearing loss in the two patients. These results provide a foundation for further elucidating the genetic factors responsible for EVA-associated NSHL. PMID- 28990113 TI - Downregulation of SYT7 inhibits glioblastoma growth by promoting cellular apoptosis. AB - Synaptotagmin-7 (SYT7) is a member of the synaptotagmin gene family, and encodes a protein that mediates the calcium-dependent regulation of membrane trafficking during synaptic transmission. A previous study demonstrated that the expression of SYT7 is associated with prostate cancer and serves an important role in development of prostate cancer. However, the roles of SYT7 in the progression of glioma remain unknown. In the present study, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis demonstrated that SYT7 was expressed in three human glioma cell lines. Western blotting and RT-qPCR analysis demonstrated the knockdown efficiency of SYT7 shRNA in 293T cells and U87MG cells. Celigo Image Cytometer Analysis, a caspase-3/7 assay, flow cytometry and an MTT assay demonstrated that the proliferation of U87MG cells was inhibited as SYT7 was downregulated by a lentiviral vector expressing SYT7 shRNA, via the promotion of cellular apoptosis. The results of the present study demonstrated that the downregulation of SYT7 inhibited glioblastoma growth by promoting cellular apoptosis, and that SYT7 may therefore be a potential target for glioma intervention. PMID- 28990115 TI - An inexact multistage fuzzy-stochastic programming for regional electric power system management constrained by environmental quality. AB - Electric power system involves different fields and disciplines which addressed the economic system, energy system, and environment system. Inner uncertainty of this compound system would be an inevitable problem. Therefore, an inexact multistage fuzzy-stochastic programming (IMFSP) was developed for regional electric power system management constrained by environmental quality. A model which concluded interval-parameter programming, multistage stochastic programming, and fuzzy probability distribution was built to reflect the uncertain information and dynamic variation in the case study, and the scenarios under different credibility degrees were considered. For all scenarios under consideration, corrective actions were allowed to be taken dynamically in accordance with the pre-regulated policies and the uncertainties in reality. The results suggest that the methodology is applicable to handle the uncertainty of regional electric power management systems and help the decision makers to establish an effective development plan. PMID- 28990116 TI - Introduction to the Special Section on Executive Functions and Externalizing Symptoms. PMID- 28990114 TI - Clinical Guidance for Managing Statin and Antimicrobial Drug-Drug Interactions. AB - PURPOSE OF REVIEW: This review discusses potential drug-drug interactions between statins and antimicrobials and provides clinician's guidance on how to manage these interactions. RECENT FINDINGS: In addition to statin utilization increasing in recent years, there is greater emphasis on using moderate to high-intensity statin doses. Statin-related adverse effects are often dose-dependent; therefore, patients may be at increased risk. Antimicrobial use has also increased in recent years, and various efforts have been implemented to ensure appropriate use of antimicrobials. Commonly used antimicrobials, such as macrolide antibiotics and azole antifungals, interact significantly with the CYP3A4 enzyme pathway similarly to lovastatin, simvastatin, and atorvastatin. Consequently, the potential for significant drug-drug interactions is increasing. In 2012, the US Food and Drug Administration strengthened warning labels for statins and dose adjustments related to drug-drug interactions. As such, it is imperative that clinicians are comfortable identifying drug-drug interactions between statins and antimicrobials and making appropriate therapy modifications as clinically warranted. Statins and antimicrobials are frequently coprescribed, and the available pharmacokinetic data supports the potential for clinically significant drug-drug interactions. Macrolides and selected antifungals can significantly increase drug levels of select statins, particularly those metabolized by the CYP3A4 pathway. Contrarily, rifampin can significantly reduce drug levels of statins, limiting their efficacy. Future research efforts should identify interventions to improve clinician recognition of these drug-drug interactions and the prevention of unwarranted statin-related adverse effects. PMID- 28990117 TI - Expression of matrix metalloproteinase 12 is highly specific for non proliferating invasive trophoblasts in the first trimester and temporally regulated by oxygen-dependent mechanisms including HIF-1A. AB - During first trimester pregnancy, trophoblast cells invade from the placenta into the maternal decidua where they anchor the placenta and remodel luminal structures like spiral arteries. This process depends on proteases secreted by invading trophoblasts, which degrade extracellular matrix (ECM). We here aimed to identify proteases particularly important for trophoblast invasion. We generated a list of proteases capable of degrading decidual ECM and trophoblast integrins using MEROPS database and compared expression of these proteases between primary trophoblasts isolated from first trimester placenta (FT, n = 3), representing an invasive phenotype, vs trophoblasts isolated from term pregnancy (TT, n = 3), representing a non-invasive trophoblast phenotype. Matrix metalloproteinase 12 (MMP12) revealed highest expression levels in FT, with absent expression in TT. In situ hybridisation and immunofluorescence localised MMP12 specifically to extravillous trophoblasts (evCT) whilst Ki67 co-staining revealed that proliferating trophoblasts of the cell columns were almost negative for MMP12. Quantification revealed a decline in MMP12 positive evCT at the end of first trimester, when oxygen levels start rising. MMP12 promoter analysis identified potential binding sites for hypoxia-inducible factor (HIF-1) and other oxygen sensitive transcription factors. Moreover, MMP12 protein was increased by low oxygen in FT in vitro and by addition of a HIF-1alpha activator. Collectively, MMP12 is a highly expressed protease specific for invasive evCT during the first trimester. MMP12 down regulation by increasing oxygen concentration enables temporal expression control of MMP12 and involves several mechanisms including HIF-1alpha. These findings suggest MMP12 involved in trophoblast invasion during the first trimester. PMID- 28990118 TI - Efficacy of long pulse Nd:YAG laser versus fractional Er:YAG laser in the treatment of hand wrinkles. AB - : There are different modalities for hand rejuvenation. Fractional Er:YAG laser and long pulse Nd:YAG laser were introduced for treating hand wrinkles. We plan to compare fractional Er:YAG laser and long pulse Nd:YAG laser in a randomized controlled double-blind design with multiple sessions and larger sample size in comparison with previous studies. Thirty-three participants with hand wrinkles entered this study. They were randomly allocated to undergo three monthly laser treatments on each hand, one with a fractional Er:YAG laser and the other with a long pulse Nd:YAG laser. The evaluations included assessment of clinical improvement determined by two independent dermatologists not enrolled in the treatment along with measuring skin biomechanical property of hands using a sensitive biometrologic device with the assessment of cutaneous resonance running time (CRRT). Moreover, potential side effects and patients' satisfaction have been documented at baseline, 1 month after each treatment, and 3 months after the final treatment session. Clinical evaluation revealed both modalities significantly reduce hand wrinkles (p value < 0.05), with no significant difference between two lasers. Mean CRRT values also decreased significantly after the laser treatment compared to those of the baseline in both laser groups. There was no serious persistent side effect after both laser treatments. Both fractional Er:YAG and long pulse Nd:YAG lasers show substantial clinical improvement of hand skin wrinkles with no serious side effects. However, combination treatment by these lasers along with the other modalities such as fat transfer could lead to better outcomes in hand rejuvenation. TRIAL REGISTRATION: IRCT2016032020468N4. PMID- 28990119 TI - Dual Src and EGFR inhibition in combination with gemcitabine in advanced pancreatic cancer: phase I results : A phase I clinical trial. AB - Pancreatic adenocarcinoma remains a major therapeutic challenge, as the poor (<8%) 5-year survival rate has not improved over the last three decades. Our previous preclinical data showed cooperative attenuation of pancreatic tumor growth when dasatinib (Src inhibitor) was added to erlotinib (EGFR inhibitor) and gemcitabine. Thus, this study was designed to determine the maximum-tolerated dose of the triplet combination. Standard 3 + 3 dose escalation was used, starting with daily oral doses of 70 mg dasatinib and 100 mg erlotinib with gemcitabine on days 1, 8, and 15 (800 mg/m2) of a 28-day cycle (L0). Nineteen patients were enrolled, yet 18 evaluable for dose-limiting toxicities (DLTs). One DLT observed at L0, however dasatinib was reduced to 50 mg (L-1) given side effects observed in the first two patients. At L-1, a DLT occurred in 1/6 patients and dose was re-escalated to L0, where zero DLTs reported in next four patients. Dasatinib was escalated to 100 mg (L1) where 1/6 patients experienced a DLT. Although L1 was tolerable, dose escalation was stopped as investigators felt L1 was within the optimal therapeutic window. Most frequent toxicities were anemia (89%), elevated aspartate aminotransferase (79%), fatigue (79%), nausea (79%), elevated alanine aminotransferase (74%), lymphopenia (74%), leukopenia (74%), neutropenia (63%), and thrombocytopenia (63%), most Grade 1/2. Stable disease as best response was observed in 69% (9/13). Median progression-free and overall survival was 3.6 and 8 months, respectively. Dasatinib, erlotinib, and gemcitabine was safe with manageable side effects, and with encouraging preliminary clinical activity in advanced pancreatic cancer. PMID- 28990120 TI - Sequential versus concomitant therapy for treatment of Helicobacter pylori infection: an updated systematic review and meta-analysis. AB - BACKGROUND: Sequential and concomitant therapies are two innovative therapies for Helicobacter pylori (H. pylori) eradication. However, the comparative efficacy and safety of these treatments are controversial. Therefore, we aimed to conduct an updated systematic review and meta-analysis of studies that compared these two treatments. METHODS: A search of PubMed, Embase, the Cochrane Library, and Web of Science was carried out. Randomized controlled trials (RCTs) that compared sequential with concomitant therapies were selected for meta-analysis. RESULTS: Twenty RCTs were included in the analysis. The eradication rate of 10-day sequential therapy was superior to that of 5-day concomitant therapy (82.09 versus 77.79%, relative risk (RR) 1.052 (95% confidence interval (CI) 1.004 1.103), P = 0.035)), similar to that of 7-day concomitant therapy (82.40 versus 86.99%, RR 0.959 (95% CI 0.874-1.053), P = 0.382), and inferior to that of 10-day concomitant therapy (78.39 versus 83.32%, RR 0.945 (95% CI 0.907-0.984, P = 0.006); the occurrence of diarrhea was higher in 10-day concomitant therapy than that in 10-day sequential therapy. Compared with the eradication rate of sequential therapy, that of concomitant therapy was higher in metronidazole resistant strains (RR 0.912 (95% CI 0.844-0.986, P = 0.020)) and strains resistant to metronidazole and clarithromycin (RR 0.542 (95% CI 0.308-0.956, P = 0.035)). CONCLUSION: The efficacy of concomitant therapy was duration dependent, and 10-day concomitant therapy was superior to 10-day sequential therapy. Compared to sequential therapy, concomitant therapy was more efficacious for metronidazole-resistant strains and metronidazole plus clarithromycin-resistant strains. However, diarrhea was more frequent with concomitant therapy than with sequential therapy. PMID- 28990121 TI - Climatic water deficit and surplus between the Carpathian Mountains and the Dniester River (1961-2012). AB - The study addresses the climatic water deficit (WD) and surplus (WE) in the area located between the heights of the Eastern Carpathians (Romania) and the Dniester River (Moldova). The objective of this study is to discover the trend of WD/WE (past and future) and its variation in space. WD and WE were calculated as the difference between the amounts of precipitation (P) and the reference evapotranspiration (ET0). The P-ET0 trend, analyzed through Mann-Kendall and t tests, was negative for 83 and 80% of the analyzed stations and the Sen's slope had values between - 0.05 mm year-1 (t test) and - 6.73 mm year-1 (Mann-Kendall test). Seasonally, the slope values of P-ET0 trends were negative during winter, spring, and summer and positive in autumn. The P-ET0 index is positive (WE) only in the Carpathian and Eastern Subcarpathian areas, whereas for the rest of the investigated territory, we found negative values (WD). WD is more pronounced as we depart from the Carpathians towards the east, but also on a north to south direction, reaching the maximum in the southeastern part of the territory. In what concerns seasonal distribution, WE is identified everywhere only in winter, whereas, in spring, summer, and autumn, WD characterizes most of the territory, with the exception of the Carpathian and Subcarpathian areas. The increasing WD will have a growing negative influence on the agriculture of the studied area. For the year 2030, we anticipate a reduction in the climate water availability with 46 mm m-2 (reference period: 1961-2012). PMID- 28990122 TI - Efficacy of resin infiltration of proximal caries in primary molars: 1-year follow-up of a split-mouth randomized controlled clinical trial. AB - OBJECTIVE: The main purpose of this split month, randomized, controlled clinical trial was evaluate the efficacy of caries infiltration in controlling the progression of non-cavitated proximal lesions in primary molars. Anxiety and time required for the caries infiltration was also evaluated. MATERIALS AND METHODS: Fifty healthy children, 5 to 9 years, presenting two primary molars with proximal caries lesions (1/2 of the enamel or outer 1/3 of dentin), were included. Lesions were randomly allocated to the test group (fluoridated toothpaste + flossing + infiltration) or to the control group (fluoridated toothpaste + flossing). Caries risk was based on the Cariogram model. The main outcome after 1-year radiographic follow up was assessed by an independent blinded examiner A facial image scale (FIS) was applied to assess dental anxiety and time required to perform the infiltration was recorded. RESULTS: Of the sample, 92.9% corresponded to high or medium caries risk. In 42 patients (1-year follow up), caries progression was observed in 11.9% (5/42) of the test lesions compared with 33.3% (14/42) of the control lesions (p < 0.05). Five control and three test lesions progressed to the middle 1/3 of dentin and were restored. No side effects were observed. Anxiety was both low before and after the treatment, and mean time required for the infiltration was 11.29 min (+/- 1.16 min). CONCLUSIONS: Caries infiltration of proximal caries lesions in primary molars is significantly more efficacious than standard therapy alone (fluoride toothpaste + flossing). CLINICAL RELEVANCE: Caries infiltration is an applicable and well-accepted method be used in children, representing a promising micro-invasive approach. PMID- 28990123 TI - Chemical composition and trophic state of shallow saline steppe lakes in central Asia (North Kazakhstan). AB - The purpose of this study was to identify the prevailing chemical composition and trophic state of the shallow saline steppe lakes of North Kazakhstan along a wide size range (< 1-454 km2) and salinity gradient (2-322 g L-1) on a large spatial scale (1000 km), taking into account the potential effects of human disturbances. Water depth, Secchi disk transparency, temperature, pH, electric conductivity, major ions, total dissolved solids, total organic carbon, total nitrogen and phosphorus, nitrate, soluble reactive phosphorus, and chlorophyll a were measured. The equivalent percentage of major ions, Spearman rank correlation, multivariate analyses, equilibrium state of lakes, and spatial GIS autocorrelation were calculated. The impact of human disturbances (settlements, farms, and mines) on total organic carbon, nitrogen, phosphorus, and chlorophyll a were tested by Kruskal-Wallis ANOVA. The most common combinations of dominant ions were Na-Cl>SO4 and Na-Cl (n = 16; 64%); the Ca, Mg, HCO3, and SO4 ions precipitate with increasing salinity (2-322 g L-1); and ion composition shifts from Na>Mg-Cl>SO4 to Na-Cl. The most of the chemical variables positively, but chlorophyll a negatively, correlated with total dissolved solids, and the total phosphorus had no significant correlation with any variables. The trophic state of these lakes in most cases exceeded the hypertrophic level. The increase in salinity causes change in chemical composition and effects on the phytoplankton development independently from the size of water surface, and the human disturbances had negligible effect on the trophic state of shallow saline lakes in this region of Kazakhstan. PMID- 28990124 TI - The induction of salt stress tolerance by propyl gallate treatment in green microalga Dunaliella bardawil, through enhancing ascorbate pool and antioxidant enzymes activity. AB - The effect of propyl gallate (PG), a synthetic antioxidant, on antioxidant responses and salinity tolerance was investigated in the cells of the green microalga, Dunaliella bardawil. Algal suspensions grown at three salinity levels of 1, 2, and 3 M NaCl were incubated with 1 mM of PG. The number of cells was significantly lower in all PG-treated cells compared to untreated controls. Despite PG-induced cell death, the fresh weight of all PG-treated cells was considerably higher than controls. PG-treated cells had enhanced antioxidant capacity because of increased levels of Chlorophyll a, beta-carotene, reduced ascorbate, protein, and enzymatic activities, but accumulated lower levels of malonyldialdehyde and hydrogen peroxide compared to untreated cells. The results suggest that PG acts as a signal molecule both directly by reducing of free radical oxidants and indirectly by augmenting ascorbate pool levels, beta carotene production, and antioxidant enzymes activity to boost the capacity of antioxidant systems and radical oxygen species scavenging. Therefore, induction of salt stress tolerance by PG in D. bardawil is associated with metabolic adjustments through activation or synthesis of both enzymatic and non-enzymatic molecules involved in antioxidant systems. PMID- 28990125 TI - Differences in range of motion with the same combined anteversion after total hip arthroplasty. AB - PURPOSE: We investigated the various impingement angles (including both bony and prosthetic impingement) and impingement types that can occur after THA, even when the same combined anteversion parameter is used. We also investigated the relationship between impingement angle and acetabular morphology or femoral anteversion. METHODS: We evaluated 83 patients with no hip arthritis. We divided them into six groups according to acetabular CE angle (<=15 degrees , >15-<=25 degrees , and >25 degrees ) and femoral anteversion (<=20 degrees and >20 degrees ). Using three-dimensional templating software, we changed stem and cup anteversion to satisfy a combined anteversion (CA) of 50 degrees in each hip (stem anteversion + cup anteversion = 50 degrees ) and investigated the resulting impingement angles. RESULTS: Even with the same CA, differences in impingement angle occurred: 18.3 degrees +/- 7.2 degrees with flexion, 30.2 degrees +/- 9.7 degrees with internal rotation at 90 degrees flexion, 20.2 degrees +/- 12.5 degrees with extension, and 26.2 degrees +/- 7.8 degrees with external rotation. As stem anteversion increased, the impingement type changed from prosthetic impingement to bony impingement in flexion and internal rotation and from bony impingement to prosthetic impingement in extension and external rotation. The flexion angle and internal rotation angle at 90 degrees flexion increased (p < 0.016) as CE angle decreased. There were no significant differences between high and low femoral anteversion. CONCLUSIONS: Combined anteversion theory should be used with care because of large differences in impingement angles. A stem anteversion of 30 degrees and cup anteversion of 20 degrees appear to be ideal for obtaining a larger impingement angle under this condition. PMID- 28990126 TI - Effectiveness and predictability of titanium-prepared platelet-rich fibrin for the management of multiple gingival recessions. AB - OBJECTIVE: Titanium-prepared platelet-rich fibrin (T-PRF) is activated with titanium, which results in a more mature and aggregated form than PRF. In our previous studies, we established that the fibrin carpet formed with titanium had a firmer network structure, and longer resorption time in the tissue than the fibrin carpet formed with glass. The purpose of this randomized controlled clinical trial is to compare the effects of autogenous T-PRF and connective tissue graft (CTG). MATERIALS AND METHODS: A total of 114 Miller Class I/II gingival recessions with abrasion defects were treated either T-PRF (63 teeth) or CTG (51 teeth) using a modified tunnel technique. Clinical periodontal indexes, keratinized tissue (KTW), gingival thickness, and recession depth were recorded before surgery and at 6- and 12-month follow-up examinations. The visual analog scale and healing index scores were assessed. RESULTS: The mean root coverages were 93.29 and 93.22% in the T-PRF and CTG groups, respectively, at 12 months post-operatively. CTG resulted in greater gingival thickness than T-PRF at 6 and 12 months post-surgery compared to baseline. Furthermore, the mean amounts of KTW increased by 1.97 and 0.75 mm in the T-PRF and CTG groups, respectively. CONCLUSION: Within the limits of this study, the results demonstrated that T-PRF is safe and effective for treatment of multiple Miller Class I/II gingival recession defects. CLINICAL RELEVANCE: T-PRF can serve as a good autogenous alternative to CTG, which is the gold standard for root coverage. PMID- 28990127 TI - Patterns of axillary evaluation in older patients with breast cancer and associations with adjuvant therapy receipt. AB - PURPOSE: Although axillary lymph node status has traditionally been a key factor in informing adjuvant breast cancer therapy recommendations, this information may be less relevant as our focus shifts more towards tumor biology, particularly in older patients where comorbidity influences treatment decisions and nodal staging and/or surgery may not improve outcomes. We examined patterns of axillary surgery and associations between axillary surgery and receipt of adjuvant treatment in older breast cancer patients. METHODS: Women aged >= 65 years with clinically node-negative, stage I-II breast cancer treated between 2012 and 2013 were identified using the National Cancer Data Base. Using multivariable logistic regression, we examined associations between axillary surgery and age, adjusting for patient, clinical, and facility factors. We also examined receipt of adjuvant treatment by nodal surgery. RESULTS: Among 68,205 women, 40.1% were aged 65-70, 24.5% were 71-75, 17.4% were 76-80, and 18.0% were > 80. Overall, 91.2% had axillary surgery (67.8% sentinel lymph node biopsy, 11.7% axillary lymph node dissection, 11.7% unspecified/unknown axillary surgery); 88.0% of those aged >= 70 with lower risk, hormone receptor-positive tumors underwent axillary surgery. In adjusted analyses, compared to patients aged 65-70, increasing age was associated with lower odds of any axillary surgery (ages 71-75: OR 0.64, 95% CI 0.57-0.71; ages 76-80: OR 0.33, 95% CI 0.30-0.37; age > 80: OR 0.08, 95% CI 0.07 0.08). Axillary surgery was associated with higher odds of receipt of radiation after breast conservation and receipt of chemotherapy in human epidermal growth factor 2-positive disease. CONCLUSIONS: In a large nationwide dataset, the vast majority of older women with clinically node-negative breast cancer underwent axillary staging despite uncertainty about its impact on survival, particularly for those with lower-risk disease. Further study on how to tailor node assessment in older patients is warranted. PMID- 28990128 TI - A single-center, retrospective analysis to compare the efficacy and safety of filgrastim-sndz to filgrastim for prophylaxis of chemotherapy-induced neutropenia and for neutrophil recovery following autologous stem cell transplantation. AB - Filgrastim-sndz (Zarxio(r)) was approved by the FDA in March 2015 as a biosimilar product of its reference product, filgrastim (Neupogen(r)) for all five indications. The NCCN Clinical Practice Guidelines has incorporated filgrastim sndz into its recommendations as a category 1 recommendation for use in settings of febrile neutropenia, myelosuppressive chemotherapy administration, and post hematopoietic stem cell transplant (HSCT). As a cost-saving initiative, our institution switched from filgrastim to filgrastim-sndz for all indications starting in March 2016. The purpose of this study was to assess for any difference in clinical or safety outcomes between filgrastim and filgrastim-sndz. This is an IRB-approved, single institution, 1-year retrospective chart review (September 2015 to August 2016) conducted in hospitalized adults who received either filgrastim or filgrastim-sndz either for prophylaxis of chemotherapy induced myelosuppression or for neutrophil recovery after autologous HSCT. Our data showed no differences in duration of G-CSF therapy (7.96 vs. 8.5 days, P = 0.36), white blood count (WBC) (8.99 vs. 8.04, P = 0.28), absolute neutrophil count (ANC) (7.62 vs. 6.91 * 109/L, P = 0.36) at the time of granulocyte-colony stimulating factor (G-CSF) discontinuation, or safety of filgrastim and filgrastim-sndz. The efficacy and safety of filgrastim and filgrastim-sndz were similar for prophylaxis of chemotherapy-induced neutropenia and neutrophil recovery post-autologous HSCT. PMID- 28990129 TI - Differences in lethal response between male and female calanoid copepods and life cycle traits to cadmium toxicity. AB - This study determined the effect of cadmium (Cd) toxicity comparatively on two copepods, Eurytemora affinis (Poppe 1880) from a temperate region (Seine Estuary, France) and Pseudodiaptomus annandalei (Sewell 1919) from a subtropical region (Danshuei Estuary, Taiwan), according to their sex and reproductive stages. In addition, the effect of Cd to their life cycle traits was quantified. In the first experiment, both copepod sexes were exposed to 40, 80, 150, 220, and 360 ug/L of Cd and a control cultured in salinity 15, except that the temperature was 18 degrees C for E. affinis and 26 degrees C for P. annandalei. This allowed calculating median lethal concentration (LC50) of Cd after 96 h. This was 120.6 ug/L Cd for P. annandalei males which were almost twice as sensitive as P. annandalei females (LC50 = 239.5 ug/L Cd). For E. affinis females, the LC50 was 90.04 ug/L Cd, reflecting a 1.4 times higher sensitivity of females than of males (LC50 = 127.75 ug/L Cd). The males of both species were similarly sensitive; however, the E. affinis females were 2.7 times more sensitive than the P. annandalei females. We also compared the sensitivity of ovigerous females (OVF) and non-ovigerous females (NOF) of both species to Cd. Mortality was higher in NOF than in OVF of both copepod species in both the control and the 40 ug/L Cd treatment. Finally, the total population, fecundity and female morphology of both copepod species were estimated after exposing one generation cycle (nauplius to adult) to 40 MUg/L Cd (for E. affinis) and 160 MUg/L Cd (for P. annandalei). A significant decrease in cohort production, survival and clutch size but no significant difference in the prosome length of both copepod species exposed to Cd were detected. The ratio of OVF:NOF was high in both copepod species exposed to Cd. Cd toxicity did not significantly affect the M:F sex ratio and % OVF of E. affinis. However, the effect of Cd toxicity in P. annandalei was significant in the M:F sex ratio and was in favor of females and their reproductive activities due to an increase in % OVF. Moreover, there was a significant decrease in total production of P. annandalei due to high mortality in their nauplii and copepodid developmental stages. Toxicity to Cd appears to be affected by multiple factors including sex, reproductive life stage and species. The ecological implication of Cd toxicity on E. affinis and P. annandalei copepod ecology is more related to a skewed sex ratio, low egg production, reduced hatchability and reduced survival that affects the recruitment potential of the copepod nauplii resulting in a decreasing copepod population. Mortality, reproduction and population growth of model species may provide important bio-indicators for environmental risk assessment. PMID- 28990130 TI - Sperm preparation after freezing improves motile sperm count, motility, and viability in frozen-thawed sperm compared with sperm preparation before freezing thawing process. AB - PURPOSE: The aim of this study is to evaluate which cryopreservation protocol, freezing before or after swim-up, optimizes cryopreservation outcomes in terms of motile sperm count, motility, morphology, and viability, and also to establish whether sperm viability could be assessed based on sperm motility. METHODS: Fifty three fresh and 53 swim-up prepared samples were considered for the first experiment. In parallel, total motility evaluation by CASA system (computer assisted sperm analyzer) and hypoosmotic swelling test (HOS-test) was performed in each sample to compare the viability results of both methods. In the second experiment, 21 normozoospermic semen samples and 20 semen samples from male factor patients were included. After fresh ejaculate evaluation, the semen sample of each patient was divided into two aliquots, one of them was frozen before swim up and the other was frozen after swim-up. Motility, sperm count, morphology, and viability were evaluated after thawing. RESULTS: A linear regression model allows prediction of HOS-test viability results based on total motility: HOS = 1.38 + 0.97 . TM (R 2 = 99.10, residual mean squares = 9.51). Freezing before sperm selection leads to higher total and progressive motility, total motile sperm count, and viability rates than when sperm selection is performed before freezing (P < 0.005 in all cases). In fact, sperm selection prior to freezing reaches critical values when subfertile patients are considered. CONCLUSIONS: To conclude, total motility evaluation can predict HOS-test viability results, resulting in a more objective and less time-consuming method to assess viability. In addition, sperm freezing prior to swim-up selection must be considered in order to achieve better outcomes after thawing, especially in patients presenting poor sperm baseline. PMID- 28990131 TI - Diagnosis and Management of Cognitive and Behavioral Changes in Dementia With Lewy Bodies. AB - OPINION STATEMENT: Proper diagnosis of dementia with Lewy bodies (DLB) in clinical practice remains suboptimal as many cases are misdiagnosed, usually as Alzheimer disease (AD) or Parkinson's disease (PD) and, in rare cases, psychosis. Therefore, it is important for patients with dementia to be thoroughly evaluated by a specialist who is familiar with current diagnostic tests and treatment options. New diagnostic criteria from the Dementia with Lewy Bodies Consortium have been developed to increase diagnostic sensitivity for DLB (Diagnosis and management of dementia with Lewy bodies: fourth consensus report of the DLB Consortium; McKeith et al.; Neurology, 89(1): 88-100). REM sleep behavior disorder (RBD) has been studied more thoroughly in correlation with DLB and is now considered a core feature. D2 receptor blocking antipsychotics, which can cause severe antipsychotic sensitivity, are now rarely prescribed for treatment. Therefore, severe antipsychotic sensitivity, which was a suggestive criterion for DLB diagnosis, is now listed as a supportive feature. Reduced DAT uptake in basal ganglia demonstrated by SPECT or PET imaging has high specificity (90%) for distinguishing DLB from AD. Reduced uptake on metaiodobenzylguanidine myocardial scintigraphy correlates with reduced postganglionic sympathetic cardiac innervation in Lewy body diseases, which can increase specificity for discriminating probable DLB from probable AD in milder cases of dementia. However, the latter is more commonly used in Japan and is not used in the USA. The evidence supporting the benefit of other therapeutic modalities is limited in DLB due to lack of extensive studies. There are no FDA-approved medications for the treatment of DLB, although some effective drugs have been used off label to treat various symptoms. PMID- 28990133 TI - Correction to: Malachite Green and Crystal Violet Decolorization by Ganoderma lucidum and Pleurotus ostreatus Supernatant and by rGlLCC1 and rPOXA 1B Concentrates: Molecular Docking Analysis. AB - The original version of this article unfortunately contained a mistake. The replacement image of Fig. 4 provided by the first corresponding author, Aura M. Pedroza-Rodriguez, is incorrect and that the originally submitted Fig. 4 should have been retained. The original article has been corrected. PMID- 28990134 TI - Evaluation of Potassium Dichromate (K2Cr2O7)-Induced Liver Oxidative Stress and Ameliorative Effect of Picrorhiza kurroa Extract in Wistar Albino Rats. AB - The aim of the study was to assess the protective effect of Picrorhiza kurroa hydroalcoholic extract (PCK), a glycoside-rich extract, against potassium dichromate (PDC)-induced liver oxidative stress in Wistar albino rats. Thirty-six male Wistar rats were divided into six groups: the control group (which received distilled water), the SIL group (which received 60 mg/kg silymarin), the PDC group (which received 30 mg/kg K2Cr2O7), and the treatment groups (which received 25, 50, 100 mg/kg PCK). Administration of PDC resulted in increased levels of liver enzymes such as alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP); up-regulated peroxidation biomarkers, i.e., thiobarbutric acid-reactive species (TBARS) and protein carbonyls in serum; and decreased activities of antioxidant enzymes like superoxide dismutase (SOD) and catalase (CAT) significantly in the liver tissue. Gene expression studies of tumor necrosis factor (TNF), mitogen-activated protein kinase (MAPK), growth arrest, and DNA damage-inducible protein (GADD45) revealed that there was a liver damage at the molecular level, and histopathological studies further confirmed the morphological changes by PDC administration. However, PCKs at 50 and 100 mg/kg promoted significant restoration of liver enzyme levels and the activities of antioxidant enzymes were kept close to the values of the control and SIL groups. Our current study confirms that the active compounds present in the PCK might have conferred a strong protection against potassium dichromate-induced oxidative stress. PMID- 28990136 TI - Hepatic Abscess with Biliary Obstruction Mimicking Cholangiocarcinoma-a Case Report. PMID- 28990135 TI - Text Messaging (SMS) Helping Cancer Care in Patients Undergoing Chemotherapy Treatment: a Pilot Study. AB - Cancer treatment is an extremely stressful life experience that is accompanied by a range of psychological, social, physical, and practical difficulties. Cancer patients need to receive information that helps them to better understand the disease, assists them in decision-making, and helps them deal with treatment. Patients are interested in receiving such information. The degree of satisfaction with the information received has been associated with positive health outcomes, specifically regarding quality of life, severity of side effects, and psychological well-being. This study investigates a method of guiding cancer patients, in relation to outpatient chemotherapy treatment, using SMS (short message service) text messaging. A smartphone application called cHEmotHErApp was developed, and its primary function is to send out SMS text messages with guidance for self-care and emotional support for oncology patients undergoing chemotherapy. Thus, the main objective of this study is to evaluate the acceptance and perception of patients of the receipt of these SMS messages, as well as to evaluate the possible benefits reported by the participants. Adult patients diagnosed with cancer, who started the first outpatient chemotherapy treatment scheme between August and November 2016 at the School Hospital (HE) of the Federal University of Pelotas (UFPel), were invited to participate in this pilot study. In total, 14 cancer patients were adherent to this study. Each of these patients received a daily text message on their cell phone with some guidance on encouraging self-care and emotional support. Patients reported that, because of the SMS text messages they received, they felt more confident in their treatment, felt more supported and encouraged, and that the text messages facilitated self-care. In addition, patients reported that the SMS text messages they received helped them to take better care of themselves and to continue further treatment. PMID- 28990132 TI - OXA-48-like carbapenemases producing Enterobacteriaceae in different niches. AB - The emergence of carbapenem-resistant enterobacterial species poses a serious threat to public health worldwide. OXA-48-type carbapenem-hydrolyzing class D beta-lactamases are widely distributed among Enterobacteriaceae, with significant geographical differences. To date, 11 OXA-48-like variants have been identified, with classical OXA-48 being the most widespread. These enzymes show high-level hydrolytic activity against penicillins and low-level hydrolysis towards carbapenems. Since the first description of the OXA-48 carbapenemase in Turkey, bacterial strains producing the enzyme have been extensively reported in nosocomial and community outbreaks in many parts of the word, particularly in the Mediterranean area and European countries. The rapid spread of Enterobacteriaceae producing OXA-48-like enzymes in different ecosystems has become a serious issue recently. The number of reservoirs for such organisms is increasing, not only in hospitals, but also in the community, among animals (e.g., livestock, companion animals, and wildlife) and in the environment. This review aims to summarize the main characteristics of the OXA-48-type carbapenemases, covering genetic and enzymatic traits, their epidemiology, clonality and associated genes, correlation with extended-spectrum beta-lactamases (ESBLs) or plasmidic AmpC (pAmpC) in different bacterial species worldwide. PMID- 28990138 TI - A survey of protocols and trends in orthodontic retention. AB - BACKGROUND: The objectives of this study were to evaluate retention procedures and protocols which are used by the orthodontists in Lithuania and to identify commonly used types of dental retainers. METHODS: One hundred seven questionnaires in total with 28 multiple-choice questions were sent to all members of the Lithuanian Orthodontic Society. The questionnaire was organized into eight sections representing specific information about socio-demographic status of the respondents, selection of a retention system, details of commonly used fixed and removable retainers, the duration of the retention period, supervision of the retainers, instructions for patients, and necessity of common retention guidelines. RESULTS: The overall response rate was 75.7%. All of the respondents prescribed retainers after the orthodontic therapy. More than 40% of the respondents combined fixed and removable retainers in different clinical situations, but the first-choice option after an expansion of the maxillary dental arch was the removable retainer (54.3%); meanwhile, a fixed retainer was used after a correction of any rotations of the mandibular anterior teeth (49.4%). The Hawley retainer was preferred by 90.1% of the respondents for a maxillary dental arch, and 74.1% of them preferred it for a mandibular dental arch. The most preferable fixed retainer was the retainer bonded to all six anterior teeth (in the upper dental arch-by 71.6%; in the lower one-by 80.2%). There was no consensus on the duration of a retention period. Most of the orthodontists checked up retainers three times during the first year (fixed ones by 42.0%; removable ones-by 30.0%) and once per year after the 1-year retention period (fixed ones-by 44.4%; removable ones-by 40.7%). All orthodontists gave instructions for taking care of an orthodontic retainer. It was observed that the orthodontists with less than 10 years of experience used a protocol based on the skills learned during their postgraduate studies, while orthodontists with more than 10 years of experience used retention procedures based on their orthodontic work practice (p < 0.05). CONCLUSIONS: A combination of fixed and removable retainers was the most often used in an orthodontic retention. Evidence-based guidelines are desired for a common retention protocol. PMID- 28990139 TI - Association between Morphological Patterns of Myometrial Invasion and Cancer Stem Cell Markers in Endometrial Endometrioid Carcinoma. AB - In endometrial endometrioid adenocarcinoma (EEC), the depth of myometrial invasion (MI) is an important parameter for determining whether additional treatment is warranted. The present study investigated the association between MI patterns, cancer stem cell (CSC) phenotypes, and their clinicopathological significance in EEC. A total of 73 cases of EEC with MI were examined in this study. Haematoxylin and eosin-stained tissue specimens were analysed for MI pattern, which was categorised as infiltrating; expansile; adenomyosis (AM)-like; or microcystic, elongated, and fragmented (MELF)-type. The expression of CSC markers such as cluster of differentiation (CD)44, CD133, and Nanog1, as well as oestrogen receptor (ER) and progesterone receptor (PR) was examined by immunohistochemistry. Clinicopathological features including age, DOI, MI pattern, LVI, lymph node (LN) metastasis, disease progression, and survival outcome were recorded. Most examined cases (45/73) were International Federation of Gynecology and Obstetrics (FIGO) stage I. MI showed infiltrating (49.3%), AM like (26.3%), MELF (15.1%), and expansile (9.6%) patterns. Tumours with the infiltrating pattern were associated with high FIGO grade (P = 0.002), reduced ER and PR, and CD44 expression (P = 0.014, 0.026, and 0.030, respectively); those with a MELF pattern showed LN metastasis (P < 0.001), lymphovascular invasion (P = 0.011), and reduced ER, CD44, and CD133 expression (P = 0.036, 0.006, and 0.016, respectively). EEC with infiltrating/MELF patterns of MI is associated with worse prognosis. These results suggest that CSC expression profiles are an unfavourable indicator of EEC. PMID- 28990137 TI - Effects of Fluoride on SOD and CAT in Testis and Epididymis of Mice. AB - Oxidative damage has been implicated to be one of main mechanisms by which fluoride (F) induces toxic effects. Previous studies reported that F destroyed the epididymal structure of mouse and rabbit. Epididymis is the important place for sperm maturation. However, little is known about the effect of F on the oxidative stress status of epididymis. Therefore, the aim of the present study was to explore the changes in the activities and transcriptional levels of CuZn superoxide dismutase (CuZn-SOD, SOD1) and catalase (CAT), as well as the ultrastructure, in testis and epididymis of mice administrated with F. Sixty health Kunming mice were randomly divided into four groups. With one group untreated as controls, the others were treated with 25, 50, and 100 mg NaF/L in drinking water. After 10 weeks administration, mitochondrial ultrastructural changes in testis and epididymis were observed, including the incomplete membrane and the dissolved or disappeared cristae. Compared to the control group, the activities of both SOD1 and CAT in testis and epididymis were significantly reduced by 50 or 100 mg NaF exposure. In addition, the mRNA expressions of testicular SOD1 and CAT were also decreased significantly in 100 mg NaF/L group, while the SOD1 and CAT mRNA expressions in epididymides were significantly reduced in all F treatment groups. The above results suggest that in the presence of F, similar to testis, epididymis also loses the balance between oxidative stress and antioxidative defense, and perhaps more sensitive to F. PMID- 28990141 TI - Same Time Next Year! PMID- 28990140 TI - Comparison of expression of key sporulation, solventogenic and acetogenic genes in C. beijerinckii NRRL B-598 and its mutant strain overexpressing spo0A. AB - The production of acetone, butanol and ethanol by fermentation of renewable biomass has potential to become a valuable industrial process. Mechanisms of solvent production and sporulation involve some common regulators in some ABE producing clostridia, although details of the links between the pathways are not clear. In this study, we compare a wild-type (WT) Clostridium beijerinckii NRRL B 598 with its mutant strain OESpo0A, in which the gene encoding Spo0A, an important regulator of both sporulation and solventogenesis, is overexpressed in terms of solvent and acid production. We also compare morphologies during growth on two different media: TYA broth, where the WT culture sporulates, and RCM, where the WT culture does not. In addition, RT-qPCR-based analysis of expression profiles of spo0A, spoIIE, sigG, spoVD, ald and buk1 genes involved in sporulation or solvent production in these strains, were compared. The OESpo0A mutant did not produce spores and butanol titre was lower compared to the WT, but increased amounts of butyric acid and ethanol were produced. The gene spo0A had high levels of expression in the WT under non-sporulating culture conditions while other selected genes for sporulation factors were downregulated significantly. Similar observations were obtained for OESpo0A where spo0A overexpression and downregulation of other sporulation genes were demonstrated. Higher expression of spo0A led to higher expression of buk1 and ald, which could confirm the role of spo0A in activation of the solventogenic pathway, although solvent production was not affected significantly in the WT and was weakened in the OESpo0A mutant. PMID- 28990142 TI - Blood Cadmium Concentrations in Women with Ectopic Pregnancy. AB - The purpose of this study is to investigate the relationship between the blood level of cadmium and the occurrence of ectopic pregnancy. Forty-one (41) case patients with ectopic pregnancy and 41 uncomplicated intrauterine pregnant patients as controls were recruited. The concentrations of cadmium (Cd) were measured from blood samples using atomic absorption spectrometry. The cases and controls were similar in age, body mass index, and smoking habits. The median blood level of Cd was 0.32 MUg/l (interquartile range [IQR] 0.00-0.71) in the women with ectopic pregnancies and 0.34 MUg/l (IQR 0.09-0.59) in the controls. There was no significant association between blood cadmium levels and ectopic pregnancy. PMID- 28990143 TI - Turning an environmental problem into an opportunity: potential use of biochar derived from a harmful marine biomass named Cladophora glomerata as anode electrode for Li-ion batteries. AB - The electrochemical performance of lithium ion battery was enhanced by using biochar derived from Cladophora glomerata (C. glomerata) as widespread green macroalgae in most areas of the Iran's Caspian sea coast. By the utilization of the structure of the biochar, micro-/macro-ordered porous carbon with olive shaped structure was successfully achieved through pyrolysis at 500 degrees C, which is the optimal temperature for biofuel production, and was activated with HCl. The biochar and HCl treatment biochar (HTB) were applied as anode electrode in lithium ion batteries. Then, electrochemical measurements were conducted on the electrodes via galvanostatic charge-discharge, cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS) analyses. The electrochemical results indicated a higher specific discharge capacity (700 mAh g-1) and good cycling stability for HTB at the current density of 0.1 A g-1 as compared to the biochar. The reason that HTB electrode works better than the biochar could be due to the higher surface area, formation functional groups, removal impurities, and formation some micropores after HCl treatment. The biochar derived from marine biomass and treatment process developed here could provide a promising path for the low-cost, renewable, and environmentally friendly electrode materials. Graphical abstract Algal-biochar into Li-ion Battery. PMID- 28990144 TI - Biofilm formation by Candida albicans is inhibited by photodynamic antimicrobial chemotherapy (PACT), using chlorin e6: increase in both ROS production and membrane permeability. AB - Candida albicans is an opportunistic fungal producing both superficial and systemic infections in immunocompromised patients. Furthermore, it has been described an increase in the frequency of infections which have become refractory to standard antifungal therapy. Photodynamic antimicrobial chemotherapy (PACT) is a potential antimicrobial therapy that combines visible light and a nontoxic dye, known as a photosensitizer, producing reactive oxygen species (ROS) that can kill the treated cells. The objective of this study was to investigate the effects of PACT, using chlorin e6, as a photosensitizer on C. albicans. In this work, we studied the effect of PACT on both cell growth and biofilm formation by C. albicans. In addition, both ROS production and cell permeability were determined after PACT. PACT inhibited both growth and biofilm formation by C. albicans. We have also observed that PACT increased both ROS production (six times) and cell membrane permeability (five times) in C. albicans. PACT decreased both cell growth and biofilm development. The effect of PACT using chlorin e6 on C. albicans could be associated with an increase in ROS production, which could increase cell permeability, producing permanent damage to the cell membranes, leading to the cell death. PMID- 28990145 TI - Organic horizon and mineral soil mercury along three clear-cut forest chronosequences across the northeastern USA. AB - Mercury (Hg) is a globally distributed pollutant trace metal that has been increasing in terrestrial environments due to rising anthropogenic emissions. Vegetation plays an important role in Hg sequestration in forested environments, but increasing tree removal for biofuels and wood products may affect this process. The long-term effect of clear-cutting on forest soil Hg remains uncertain, since most studies are limited to measuring changes for < 10 years following a single harvest event. The chronosequence approach, which substitutes space for time using forest stands of different ages since clear-cutting, allows for investigation of processes occurring over decades to centuries. Here, we utilized three clear-cut forest soil chronosequences across the northeastern USA to understand Hg accumulation and retention over several decades. Total Hg concentrations and pools were quantified for five soil depth increments along three chronosequences. Our results showed Hg concentrations and pools decreased in the initial 20 years following clear-cutting. Mineral soil Hg pools decreased 21-53% (7-14 mg m-2) between 1-5-year-old stands and 15-25-year-old stands but mineral soil Hg pools recovered in 55-140-year-old stands to similar values as measured in 1-5-year-old stands. Our study is one of the first to demonstrate a decrease and recovery in Hg pool size. These changes in Hg did not correspond with changes in bulk density, soil C, or pH. We utilized a simple two-box model to determine how different Hg fluxes affected organic and mineral soil horizon Hg pools. Our simple model suggests that changes in litterfall and volatilization rates could have caused the observed changes in organic horizon Hg pools. However, only increases in leaching could reproduce observed decreases to mineral soil Hg pools. Further studies are needed to determine the mechanism of Hg loss from forest soils following clear-cutting. PMID- 28990146 TI - A preliminary study to design a floating treatment wetland for remediating acid mine drainage-impacted water using vetiver grass (Chrysopogon zizanioides). AB - Acid mine drainage (AMD) is extremely acidic, sulfate-rich effluent from abandoned or active mine sites that also contain elevated levels of heavy metals. Untreated AMD can contaminate surface and groundwater and pose severe ecological risk. Both active and passive methods have been developed for AMD treatment consisting of abiotic and biological techniques. Abiotic techniques are expensive and can create large amounts of secondary wastes. Passive biological treatment mainly consists of aerobic or anaerobic constructed wetlands. While aerobic wetlands are economical, they are not effective if the pH of the AMD is < 5. Anaerobic wetlands use organic-rich substrates to provide carbon source to iron- and sulfate-reducing bacteria. The efficiency of these systems declines overtime and requires continuous maintenance. Our objective is to develop an alternative, low-cost, and sustainable floating wetland treatment (FWT) system for AMD for the abandoned Tab-Simco coal mining site in Illinois using vetiver grass (Chrysopogon zizanioides). Tab-Simco AMD is highly acidic, with mean pH value of 2.64, and contains high levels of sulfate and metals. A greenhouse study was performed for a 30-day period in order to screen and optimize the necessary parameters to design a FWT system. Water quality and plant growth parameters were continuously monitored. Results show significant SO42- removal, resulting in increased pH, particularly at higher planting densities. Vetiver also helped in metal removal; high amounts of Fe, Zn, and Cu were removed, with relatively lower amounts of Pb, Al, and Ni. Iron plaque formation on the root was observed, which increased metal stabilization in root and lowered root to shoot metal translocation. Vetiver was tolerant of AMD, showing minimal change in biomass and plant growth. Results obtained are encouraging, and a large scale mesocosm study is now in progress, as the next step to develop the vetiver-based system for AMD treatment. PMID- 28990148 TI - Athletes and the Aorta: Normal Adaptations and the Diagnosis and Management of Pathology. AB - OPINION STATEMENT: Over a hundred years ago, physicians first recognized that participation in regular, vigorous training resulted in enlargement of the heart. Since that time, the term "athlete's heart" has entered the medical lexicon as a global expression encompassing the electrical, functional, and morphological adaptations that develop in response to physical training. Exercise-induced adaptations of the aorta, which is also exposed to large hemodynamic stresses during prolonged endurance exercise or resistance training, are less well recognized. Young athletes tend to have slightly larger aortas than their sedentary counterparts; however, this rarely exceeds normal ranges for the general population. A systematic approach is advised when presented with an athlete with aortic enlargement. The size of the aorta needs to be first put in the context of the athlete's age, sex, size, and sporting endeavors; however, even in the largest young athletes, the aortic root rarely exceeds 4 cm in men or 3.4 cm in women. A comprehensive evaluation is advised which includes a detailed family history and a thorough physical examination evaluating for signs of any defined connective tissue disorder associated with aortopathy. Downstream testing is then tailored for the individual and may include further tomographic imaging, opthalmology review, and genetic testing. This should ideally be performed at a specialist center. Management of athletes with an aortopathy includes tailoring athletic activity, medical management with strict impulse control, and, in some cases, prophylactic surgery. The issue of sporting eligibility should be individualized and if disqualification is necessary, this should be undertaken by a sports cardiologist or an expert in aortic disease with experience in dealing with an athletic population. PMID- 28990147 TI - Pandemrix(r) vaccination is not associated with increased risk of islet autoimmunity or type 1 diabetes in the TEDDY study children. AB - AIMS/HYPOTHESIS: During the A/H1N1 2009 (A/California/04/2009) pandemic, mass vaccination with a squalene-containing vaccine, Pandemrix(r), was performed in Sweden and Finland. The vaccination was found to cause narcolepsy in children and young adults with the HLA-DQ 6.2 haplotype. The aim of this study was to investigate if exposure to Pandemrix(r) similarly increased the risk of islet autoimmunity or type 1 diabetes. METHODS: In The Environmental Determinants of Diabetes in the Young (TEDDY) study, children are followed prospectively for the development of islet autoimmunity and type 1 diabetes. In October 2009, when the mass vaccination began, 3401 children at risk for islet autoimmunity and type 1 diabetes were followed in Sweden and Finland. Vaccinations were recorded and autoantibodies against insulin, GAD65 and insulinoma-associated protein 2 were ascertained quarterly before the age of 4 years and semi-annually thereafter. RESULTS: By 5 August 2010, 2413 of the 3401 (71%) children observed as at risk for an islet autoantibody or type 1 diabetes on 1 October 2009 had been vaccinated with Pandemrix(r). By 31 July 2016, 232 children had at least one islet autoantibody before 10 years of age, 148 had multiple islet autoantibodies and 96 had developed type 1 diabetes. The risk of islet autoimmunity was not increased among vaccinated children. The HR (95% CI) for the appearance of at least one islet autoantibody was 0.75 (0.55, 1.03), at least two autoantibodies was 0.85 (0.57, 1.26) and type 1 diabetes was 0.67 (0.42, 1.07). In Finland, but not in Sweden, vaccinated children had a lower risk of islet autoimmunity (0.47 [0.29, 0.75]), multiple autoantibodies (0.50 [0.28, 0.90]) and type 1 diabetes (0.38 [0.20, 0.72]) compared with those who did not receive Pandemrix(r). The analyses were adjusted for confounding factors. CONCLUSIONS/INTERPRETATION: Children with an increased genetic risk for type 1 diabetes who received the Pandemrix(r) vaccine during the A/H1N1 2009 pandemic had no increased risk of islet autoimmunity, multiple islet autoantibodies or type 1 diabetes. In Finland, the vaccine was associated with a reduced risk of islet autoimmunity and type 1 diabetes. PMID- 28990149 TI - Management of Arrhythmias in Athletes: Atrial Fibrillation, Premature Ventricular Contractions, and Ventricular Tachycardia. AB - OPINION STATEMENT: Management of atrial fibrillation, premature ventricular contractions, and ventricular tachycardia without underlying cardiac disease or arrhythmogenic conditions differs in athletes from the general population. Athletes tend to be younger, healthier individuals with few comorbidities. Therapies that work well in the general population may not be appropriate or preferable for athletes. Management strategies include deconditioning, pharmacologic therapy, such as rate control with beta-blockers or non dihydropyridine calcium channel blockers and rhythm control with class I or class III antiarrhythmic drugs, and catheter ablation. Deconditioning is not preferred by athletes because of lost playing time. Pharmacologic therapy is well tolerated among most individuals, but is not as favorable in athletes. Rate control medications can reduce performance and beta-blockers, in particular, are prohibited in many sports. Antiarrhythmic drugs are preferred over rate control with athletes, but many, especially younger athletes, may not like the idea of long-term medical therapy. Catheter ablation has been proven to be safe and efficacious, may eliminate the need for long-term medical therapy, and is supported by the major societies (AHA, ACC, ESC). PMID- 28990150 TI - Biomarkers of Colorectal Cancer Risk Decrease 6 months After Roux-en-Y Gastric Bypass Surgery. AB - PURPOSE: The impact of weight loss on obesity-related colorectal cancer (CRC) risk is not well defined. Previous studies have suggested that Roux-en-Y gastric bypass (RYGB) surgery may have an unexpected adverse impact on CRC risk. This study aimed to investigate the impact of RYGB on biomarkers of CRC risk. MATERIALS AND METHODS: Rectal mucosal biopsies and blood were obtained from patients undergoing RYGB (n = 22) and non-obese control participants (n = 20) at baseline and at a median of 6.5 months after surgery. Markers of systemic inflammation and glucose homeostasis were measured. Expression of pro inflammatory genes and proto-oncogenes in the rectal mucosa was quantified using qPCR. Crypt cell proliferation state of the rectal mucosa was assessed by counting mitotic figures in whole micro-dissected crypts. RESULTS: At 6.5 months post-surgery, participants had lost 29 kg body mass and showed improvements in markers of glucose homeostasis and in systemic inflammation. Expression of pro inflammatory genes in the rectal mucosa did not increase and COX-1 expression fell significantly (P = 0.019). The mean number of mitoses per crypt decreased from 6.5 to 4.3 (P = 0.028) after RYGB. CONCLUSION: RYGB in obese adults led to lower rectal crypt cell proliferation, reduced systemic and mucosal markers of inflammation and improvements in glucose regulation. These consistent findings of reduced markers of tumourigenic potential suggest that surgically induced weight loss may lower CRC risk. PMID- 28990151 TI - Burnout and stress amongst interns in Irish hospitals: contributing factors and potential solutions. AB - BACKGROUND: The transition from medical school to internship can be daunting for newly qualified doctors. High rates of stress and burnout have been reported, with negative impacts on patient care and physician wellbeing. AIMS: We surveyed interns in our hospital group to evaluate rates of stress and burnout, as well as identify the causative factors and propose potential solutions to these. METHODS: A hundred and one interns working in four different hospitals over a 2-year period were invited to participate in an anonymous survey. The survey collected basic demographic details and surveyed aspects of mental health using the burnout scale, Maslach Burnout Inventory (MBI) and the stress scale and 12-item General Health Questionnaire (GHQ-12). Interns were also asked to rate a variety of workplace factors on a Likert scale based on the degree of stress caused. Finally, they were surveyed on their awareness of support services available to them. RESULTS: Our results showed that 37% of interns met the criteria for psychological distress, high levels of emotional exhaustion, high depersonalisation and a low sense of personal accomplishment were reported in 55.4, 51.5 and 41.6%, respectively. Inadequate preparation for practice, financial worries, poor role definition and sleep deprivation were reported as significant stressors. Most were unaware of available support services and expressed interest in leaving Ireland after internship. CONCLUSIONS: Burnout and stress are significant problems amongst doctors in Irish hospitals. Ensuring better preparation for clinical practice and awareness of support services is vital to tackle this issue. PMID- 28990153 TI - Executive Functions and Externalizing Symptoms: Common and Unique Associations. AB - In discussing the four papers in this special issue, we provide our perspective on the authors' contributions and suggest directions for future research. First, we highlight the usefulness of the bi-factor model for investigating relations among specific aspects of executive functions (EFs) and externalizing symptoms. Next, we examine the role of EFs as a protective factor that can moderate the relation between risk factors - specifically, callous-unemotional behaviors - on externalizing symptoms. And finally, we address the contributions of innovative measurement approaches to understanding the relations between EFs and externalizing symptoms, using the state-space grid methodology as an example. PMID- 28990154 TI - Into the Great Unknown Our Patients Go. PMID- 28990152 TI - Therapeutic Targets for the Multi-system Pathophysiology of Heart Failure: Exercise Training. AB - OPINION STATEMENT: Adult chronic heart failure (HF) is a terminal syndrome. While the HF phenotype is inhomogeneous across the ejection fraction spectrum, exercise intolerance remains a cardinal feature of all HF patients. Impairment of a single organ system cannot independently account for exercise intolerance in HF. Thus, the multi-system integrative pathophysiology of HF leads to challenges in identifying an effective medical therapy aimed at targeting a single mechanism to improve exercise tolerance. This unresolved medical care approach raises a number of points for discussion in this field as it is well-recognized that exercise intolerance is accompanied by increased hospitalizations and mortality across the HF spectrum. Practitioner-guided individualized exercise training represents an intrinsic multi-level therapeutic approach that inclusively "targets" integrated physiological systems. A rapidly evolving body of evidence provides firm support that structured exercise therapy is safe while leading to improved exercise tolerance (peak oxygen uptake [VO2]) followed by reduced hospitalizations and cardiovascular mortality across the HF spectrum. The benefits of guided exercise therapy in HF have been directly attributed to integrative improvements in peak VO2, skeletal muscle strength, cardiac function, micro- to macro-vascular function, circulation/organ perfusion, and nervous system function, among others. Despite the sound clinical evidence in support of exercise-based medical care, there remains an appreciable gap in translation of current scientific evidence and implementation of this therapeutic paradigm into routine clinical practice as well as universal insurance coverage for HF patients. In the following review, the theme of discussion is framed in a manner that carries a sense of urgency for the need to increase awareness of the up-to-date evidence-based support for the clinical implementation of structured exercise therapy as a necessary routine component of primary medical care practices for reducing hospitalizations, morbidity, and mortality in all HF patients. PMID- 28990156 TI - Microtubule-associated protein 1A/1B-light chain 3 (LC3) 'decorates' intracytoplasmic inclusions in a patient with chronic lymphocytic leukaemia. PMID- 28990155 TI - Treatment decisions and employment of breast cancer patients: Results of a population-based survey. AB - BACKGROUND: Many patients with breast cancer work for pay at the time of their diagnosis, and the treatment plan may threaten their livelihood. Understanding work experiences in a contemporary population-based sample is necessary to inform initiatives to reduce the burden of cancer care. METHODS: Women who were 20 to 79 years old and had been diagnosed with stage 0 to II breast cancer, as reported to the Georgia and Los Angeles Surveillance, Epidemiology, and End Results registries in 2014-2015, were surveyed. Of the 3672 eligible women, 2502 responded (68%); 1006 who reported working before their diagnosis were analyzed. Multivariate models evaluated correlates of missing work for >1 month and stopping work altogether versus missing work for <=1 month. RESULTS: In this diverse sample, most patients (62%) underwent lumpectomy; 16% underwent unilateral mastectomy (8% with reconstruction); and 23% underwent bilateral mastectomy (19% with reconstruction). One-third (33%) received chemotherapy. Most (84%) worked full-time before their diagnosis; however, only 50% had paid sick leave, 39% had disability benefits, and 38% had flexible work schedules. Surgical treatment was strongly correlated with missing >1 month of work (odds ratio [OR] for bilateral mastectomy with reconstruction vs lumpectomy, 7.8) and with stopping work altogether (OR for bilateral mastectomy with reconstruction vs lumpectomy, 3.1). Chemotherapy receipt (OR for missing >1 month, 1.3; OR for stopping work altogether, 3.9) and race (OR for missing >1 month for blacks vs whites, 2.0; OR for stopping work altogether for blacks vs whites, 1.7) also correlated. Those with paid sick leave were less likely to stop working (OR, 0.5), as were those with flexible schedules (OR, 0.3). CONCLUSIONS: Working patients who received more aggressive treatments were more likely to experience substantial employment disruptions. Cancer 2017;123:4791-9. (c) 2017 American Cancer Society. PMID- 28990157 TI - Maternal adherence with recommendations for folic acid and iodine supplements: A cross-sectional survey. AB - We conducted a survey of 535 New Zealand women to determine supplement use pre pregnancy, during pregnancy and while breastfeeding to evaluate adherence with national recommendations for folic acid and iodine supplementation. Our findings suggest that despite these women being well-educated and motivated to complete an online survey, there was low adherence to recommendations for folic acid and iodine supplements. Only 38% of women reported supplement intake that met both folic acid and iodine recommendations. This cross-sectional survey provides information useful to policy makers, clinicians and researchers seeking to protect and promote maternal and infant health. PMID- 28990158 TI - Recurrent nevus as a pitfall of melanoma diagnosis under reflectance confocal microscopy. PMID- 28990159 TI - Neuropsychiatric comorbidity among adolescents with psoriasis. AB - BACKGROUND: Psoriasis is a known risk factor for neuropsychiatric diseases among adults. Less is known about the impact on adolescents. OBJECTIVES: To investigate the association between psoriasis and neuropsychiatric comorbidity and social skills among adolescents. METHODS: A population-based cross-sectional study between 1 January 1999 and 1 January 2014 was conducted. The study included 1746 and 1366 adolescents (aged 16 to 18) with mild and moderate-to-severe psoriasis, respectively. The psoriasis patients were diagnosed by a dermatologist. Neuropsychiatric diseases were diagnosed by a neurologist and a psychiatrist, as appropriate. Social skills were evaluated using psychosocial assessment. Patients with psoriasis were compared with 884 653 healthy controls by a multivariate analysis adjusted for age, sex, country of origin, socioeconomic status, cognitive skills and body mass index. A subgroup evaluation was done for comorbidity that could only be evaluated for part of the recruitment years, using a univariate analysis. RESULTS: Overall chronic headaches (8.1% vs. 3.4%), intermediate frequency migraine (4.8% vs. 1.6%), low-frequency migraine and nonmigraine headaches (3.4% vs. 1.8%) were associated with moderate-to-severe psoriasis only compared with healthy controls [adjusted odds ratios (OR) 1.9, 95% confidence interval (CI) 1.6-2.4; 2.3, 95% CI 1.8-3.0 and 1.5, 95% CI 1.1-2.1, respectively]. Anxiety disorders (2.1% vs. 0.8%) and impaired social adjustment skills (7.5% vs. 4.2%) were also associated with moderate-to-severe psoriasis only compared with healthy controls [adjusted ORs 2.9, 95% CI 1.6-5.5 and 1.9, 95% CI 1.3-2.6 (of 466 vs. 265 023), respectively]. CONCLUSIONS: Psoriasis among adolescents is associated with neuropsychiatric comorbidity and impaired adjustment skills, depending on disease severity. PMID- 28990160 TI - Monitoring of Potentially Inappropriate Prescriptions in Older Inpatients: A French Multicenter Study. AB - OBJECTIVES: To determine whether potentially inappropriate medications (PIMs) or potentially inappropriate associations (PIAs) prescribed knowingly are associated with patient monitoring. DESIGN: Prospective observational study. SETTING: Geriatric units (n = 56) in 28 hospitals. PARTICIPANTS: Inpatients aged 75 and older (N = 1,327). MEASUREMENTS: Potentially inappropriate prescriptions (PIP) were defined as a PIM or a PIA selected by an expert board from lists of explicit criteria (Beers, Priscus, Laroche, French Health Agency) using a Delphi process. They were considered to be prescribed knowingly if they were maintained after reassessment by the geriatrician and the clinical pharmacist. Primary outcome was the rate of PIPs maintained (prescribed knowingly) and for which a geriatrician declared that specific monitoring was performed. Secondary outcomes were the parameters monitored and the rate of participants receiving knowingly a PIP. RESULTS: One thousand sixty-three PIPs were detected in 607 participants (46%). After reassessment, 826 (78%) PIPs were maintained in 490 participants (37%), the main reasons being participant's regular treatment and lack of alternative. Psychotropic (36%), cardiovascular (including antithrombotics) (29%), and laxative or antiemetic drugs (16%) were the most-frequent classes prescribed knowingly. The geriatricians declared to perform clinical or biological monitoring for 69% (n = 570) of PIMs or PIAs prescribed knowingly. Three types of specific monitoring were identified: clinical, biological, and follow-up with a specialist. CONCLUSION: Approximately three-quarters of PIMs or PIAs were prescribed knowingly, of which 69% were monitored, with wide variations in occurrence and in quality according to drug classes. This underlines the need for accurate guidelines on PIP monitoring. PMID- 28990161 TI - Real-time ultrasound-guided axillary vein cannulation in children: a randomised controlled trial. AB - The axillary vein is a good site for ultrasound-guided central venous cannulation in terms of infection rate, patient comfort and its anatomical relationship with the clavicle and lungs. We compared real-time ultrasound-guided axillary vein cannulation with conventional infraclavicular landmark-guided subclavian vein cannulation in children. A total of 132 paediatric patients were randomly allocated to either ultrasound-guided axillary vein (axillary group) or landmark guided subclavian vein (landmark group). The outcomes measured were success rate after two attempts, first-attempt success rate, time to cannulation and complication rate. The success rate after two attempts was 83% in the axillary group compared with 63% in the landmark group (odds ratio 2.85, 95%CI 1.25-6.48, p = 0.010). The first-attempt success rate was 46% for the axillary group and 40% for the landmark group (p = 0.274) and median time to cannulation was 156 s for the axillary group and 180 s for the landmark group (p = 0.286). There were no differences in complication rates between the two groups, although three episodes of subclavian artery puncture occurred in the landmark group (p = 0.08). We conclude that axillary vein cannulation using a real-time ultrasound-guided in plane technique is useful and effective in paediatric patients. PMID- 28990162 TI - Vince Lombardi and Me. PMID- 28990163 TI - Corticosteroids in Duchenne muscular dystrophy: impact on the motor function measure sensitivity to change and implications for clinical trials. AB - AIM: To monitor the evolution of the motor function of ambulatory patients with Duchenne muscular dystrophy (DMD) treated by corticosteroids for 2 years in comparison with untreated patients. METHOD: This observational, multicentre cohort study explores the evolution of the motor function measure (MFM) over a 24 month period for 29 ambulant corticosteroids-treated and 45 ambulant untreated patients with DMD. RESULTS: Significant differences were found between mean MFM scores in corticosteroids-treated and untreated groups for domain 1 of the MFM (standing position and transfers; D1), domain 2 of the MFM (axial and proximal motor function; D2), and domain 3 of the MFM (distal motor function; D3). Subscores were between 0 months and 6 months, and 0 months and 24 months. For the D1 subscore specifically, there was a significant increase in the corticosteroids treated group (mean+/-standard deviation [SD] slope of change=12.6+/-15.5%/y), while a decrease was observed in the untreated group (-17.8+/-17.7%/y) between 0 months and 6 months (p<0.001). Sensitivity to change as assessed by standardized response means was high between 12 months and 24 months for D1 of both corticosteroids-treated and untreated groups (1.0 and 1.2 respectively), and low for D2 and D3 of both treated and untreated groups. INTERPRETATION: Patients with DMD treated by corticosteroids present a different course of the disease as assessed by MFM, confirming the sensitivity to change of the MFM in this population. WHAT THIS PAPER ADDS: Corticosteroids have a quantitative impact on muscle strength 6 to 24 months after starting treatment. Motor function measure is a valid outcome measure in Duchenne muscular dystrophy patients under corticosteroid treatment. PMID- 28990164 TI - Reply to 'Impact of biologic therapies on risk of major adverse cardiovascular events in patients with psoriasis: systematic review and meta-analysis of randomized controlled trials': reply from the authors. PMID- 28990165 TI - Framingham-Based Cardiovascular Risk Estimates Among People With Episodic Migraine in the US Population: Results from the American Migraine Prevalence and Prevention (AMPP) Study. AB - BACKGROUND: Cardiovascular (CV) events, conditions, and procedures (ECPs) are common in persons with migraine and are a contraindication to triptan and ergot use. In a prior study, we estimated that there are 2.6 million American adults with episodic migraine (EM) who have had CV ECPs. However, the prior analysis did not assess persons with migraine without CV ECPs who are at high risk for a first cardiovascular disease (CVD) event. OBJECTIVES: To use the Framingham nonlaboratory CVD events risk equation to estimate the number of individuals with EM who are at elevated risk for a first CVD event in the next 10 years using data from the American Migraine Prevalence and Prevention Study, and then to extrapolate the findings to the US population to estimate the scope of people with EM for whom triptan and ergot therapies may be problematic. METHODS: Data from respondents to the 2009 American Migraine Prevalence and Prevention (AMPP) Study questionnaire aged >=22 who met criteria and headache day frequency for EM were included in this cross-sectional analysis. Ten-year, first CVD event risk was calculated using the nonlaboratory Framingham CV disease risk score (FRS). Variables were collected via respondent self-report and included sex, age, height, and weight to calculate body mass index (BMI), smoking status, and the presence of hypertension and diabetes among other variables. Standard FRS cut scores of >=21 for women and >=16 for men were used, which indicate a 30% or greater risk of a first CVD event in the next 10 years. History of CV ECPs was collected via self-report of ever having the ECP and for events and conditions that were diagnosed by a physician. We applied rates of positive ECPs and rates of high FRS to age and sex stratified estimates of the number of people with EM in the US derived from 2015 US Census data to estimate rates of both in the population. RESULTS: The AMPP Study analysis sample included 5227 women and 1496 men with EM. Results showed that 69.5% of women and 73.4% of men had at least one CV risk factor from the FRS, 38.9% of women and 41.6% of men had >=2 risk factors, and 18.6% of women and 19.1% of men had >=3 risk factors. The proportion of women with high FRS was 0% for those aged 22-39, 0.8% (95%CI: 0.5-1.2%) among 40- to 59-year-olds and 15.2% (95% CI: 13.3-17.4%) among the >=60 age group. For men, the corresponding proportions were 0, 7.3% (95% CI: 5.7-9.4%), and 53.0% (95% CI: 4.7-58.1%). Projecting to a national US sample, the number of persons with EM and high FRS was 403,000 for women and 510,000 for men. The proportion of women and men at high risk for future CV events based on a prior CV ECP, a high FRS or both increased with age from 20-39 (women 4.5%, men 4.2%), 40-59 (women 11.8%, men 18.6%), and >=60 (women 31.2%, men 61.8%). An estimated 141,000 men aged 40-59 and 187,000 aged >=60 and 34,000 women aged 40-59 and 181,000 women aged >=60 in the US population with EM have not had a CV ECP but are at increased risk for a future CV event within the next 10 years based upon their FRS alone. CONCLUSION: Among people with EM in the US population, the number of women and men with relative contraindications to triptans and ergots based on a high FRS includes over 900,000 women and men. This includes more than half a million individuals with EM who have not had a prior CV ECP. PMID- 28990166 TI - Testing the keystone community concept: effects of landscape, patch removal, and environment on metacommunity structure. AB - Although the influence of regional processes on local patches is well studied, the influence of local patches and their spatial arrangement on regional processes is likely to be complex. One interesting idea is the keystone community concept (KCC); this posits that there may be some patches that have a disproportionately large effect on the metacommunity compared to other patches. We experimentally test the KCC by using replicate protist microcosm metacommunities with single-patch removals. Removing single patches had no effect on average community richness, evenness and biomass of our metacommunities, but did cause metacommunities to be assembled significantly less by local environmental conditions and more by spatial effects related to stochastic factors. Overall our results show that local patch removal can have large regional effects on structural processes, but indicate that more experiments are needed to find evidence of keystone communities. PMID- 28990167 TI - Irradiance, as well as body site and timing of readings, is important in determining ultraviolet A minimal erythemal dose: reply from the authors. PMID- 28990168 TI - Automated analysis of seizure semiology and brain electrical activity in presurgery evaluation of epilepsy: A focused survey. AB - Epilepsy being one of the most prevalent neurological disorders, affecting approximately 50 million people worldwide, and with almost 30-40% of patients experiencing partial epilepsy being nonresponsive to medication, epilepsy surgery is widely accepted as an effective therapeutic option. Presurgical evaluation has advanced significantly using noninvasive techniques based on video monitoring, neuroimaging, and electrophysiological and neuropsychological tests; however, certain clinical settings call for invasive intracranial recordings such as stereoelectroencephalography (SEEG), aiming to accurately map the eloquent brain networks involved during a seizure. Most of the current presurgical evaluation procedures focus on semiautomatic techniques, where surgery diagnosis relies immensely on neurologists' experience and their time-consuming subjective interpretation of semiology or the manifestations of epilepsy and their correlation with the brain's electrical activity. Because surgery misdiagnosis reaches a rate of 30%, and more than one-third of all epilepsies are poorly understood, there is an evident keen interest in improving diagnostic precision using computer-based methodologies that in the past few years have shown near human performance. Among them, deep learning has excelled in many biological and medical applications, but has advanced insufficiently in epilepsy evaluation and automated understanding of neural bases of semiology. In this paper, we systematically review the automatic applications in epilepsy for human motion analysis, brain electrical activity, and the anatomoelectroclinical correlation to attribute anatomical localization of the epileptogenic network to distinctive epilepsy patterns. Notably, recent advances in deep learning techniques will be investigated in the contexts of epilepsy to address the challenges exhibited by traditional machine learning techniques. Finally, we discuss and propose future research on epilepsy surgery assessment that can jointly learn across visually observed semiologic patterns and recorded brain electrical activity. PMID- 28990170 TI - Response to Ciuculete et al. PMID- 28990169 TI - Methylphenidate, cognition, and epilepsy: A 1-month open-label trial. AB - OBJECTIVE: Cognitive difficulties are common in epilepsy. Beyond reducing seizures and adjusting antiepileptic medications, no well-validated treatment exists in adults. Methylphenidate is used effectively in children with epilepsy and attention-deficit/hyperactivity disorder, but its effects in adults have not been systematically evaluated. We hypothesized that methylphenidate can safely improve cognition in adults with epilepsy. We detail here the open-label follow up to a double-blind, placebo-controlled, single-dose study. METHODS: Thirty epilepsy patients entered a 1-month open-label methylphenidate trial after a double-blind phase. Doses were titrated according to clinical practice and patient tolerance, ranging 20-40 mg/day. Primary measures included: Conners' Continuous Performance Test (CPT), Symbol-Digit Modalities Test (SDMT), and Medical College of Georgia Memory Test (MCG). Secondary measures were: Beck Depression Inventory, 2nd Edition (BDI-II), Beck Anxiety Inventory, Apathy Evaluation Scale (AES), Stimulant Side-Effect Checklist, Adverse Events Profile, Quality of Life in Epilepsy-89 (QOLIE-89), and seizure frequency. Fourteen healthy, nonmedicated controls were tested concurrently. RESULTS: Twenty-eight participants with epilepsy (13 men/15 women) completed the trial. Withdrawals occurred due to anxiety (n = 1) and fatigue (n = 1). Mean age was 36.4 years (range = 20-60). Epilepsy types were: focal (n = 21), generalized (n = 6), or unclassified (n = 1). Mean epilepsy duration was 12.3 years. Mean baseline seizure frequency was 2.8/month. There were significant improvements on methylphenidate for SDMT, MCG, CPT (the ability to discriminate between targets and nontargets [d'] hits, hit reaction time standard deviation, omissions, and commissions), and QOLIE subscales (energy/fatigue, attention/concentration, memory, and language; paired t tests; p <= 0.002). BDI-II and additional subscales also improved, at a lower level of statistical significance. Effect sizes were moderate to large. Comparisons with untreated controls (n = 14) revealed greater improvement for epilepsy patients on omissions and commissions, with improvement trends on d' and hits. Seizure frequency did not increase with methylphenidate treatment (2.8/month vs. 2.4/month). SIGNIFICANCE: Methylphenidate may be an effective and safe option for improving cognition and quality of life in epilepsy. Larger and longer double-blind, placebo-controlled clinical trials are needed. PMID- 28990171 TI - Response to Lefebvre et al. AB - Congenital scoliosis (CS) is a common vertebral malformation with incidence of up to 1 of 1000 births worldwide. Recently, TBX6 has been reported as the first disease gene for CS: about 10% of CS patients are compound heterozygotes of rare null mutations and a common haplotype composed by 3 SNPs in TBX6. Lefebvre et al in this journal reported that 2 patients with spondylocostal dysostosis (SCD), a rare skeletal dysplasia affecting spine and ribs also have TBX6 mutations: 1 carried the microdeletion and a rare missense variant, and another 2 rare missense variants. We investigated the pathogenicity of the 3 missense variants in SCD by a luciferase assay. The results were negative for the proposal of Lefebvre et al. We consider these 2 SCD patients are more probably compound heterozygotes of null mutations and a common risk haplotype just as CS patients with TBX6 mutations. PMID- 28990172 TI - Response to Leusink et al. PMID- 28990173 TI - Optimization of rituximab for the treatment of DLBCL: increasing the dose for elderly male patients. AB - Male sex is associated with unfavourable pharmacokinetics and prognosis in elderly patients with diffuse large B-cell lymphoma (DLBCL). We investigated higher rituximab doses for elderly male DLBCL patients. Elderly patients (61-80 years) received 6 cycles CHOP-14 (cyclophosphamide, doxorubicin, vincristine and prednisone at 14-day intervals) and were randomized to 8 cycles rituximab (males 500 mg/m2 , females 375 mg/m2 ) every 2 weeks or according to an upfront dose dense schedule. In 268 (120 females, 148 males) no difference between the standard and the upfront dose-dense rituximab schedule was found (3-year PFS 72% vs. 74%; OS 74% vs. 77%; P = 0.651). The 500 mg/m2 dose of rituximab for male patients was associated with serum levels and exposure times slightly better than in females and a male/female hazard ratio of 0.9 for progression-free survival (PFS) and 0.8 for overall survival. For elderly males, 500 mg/m2 was not more toxic than 375 mg/m2 rituximab, but improved PFS by 32.5% (P = 0.039), with a trend for a (30%) better overall survival (P = 0.076) in a planned subgroup analysis adjusting for International Prognostic Index risk factors. We conclude that the higher rituximab dose for elderly male patients abrogated the adverse prognosis of male sex without increasing toxicity. In the era of personalized medicine, sex-specific pharmacokinetics and toxicities should be investigated for all drugs where these parameters impact on outcome. PMID- 28990174 TI - Immunoparesis defined by heavy+light chain suppression is a novel marker of long term outcomes in cardiac AL amyloidosis. AB - Cardiac involvement and presenting dFLC (difference between involved and uninvolved free light chains) are independent predictors of outcome in systemic AL amyloidosis. These markers have limited prognostic utility in patients surviving the initial months following diagnosis. Here we assessed immunoparesis, as determined by novel heavy+light chain (HLC) immunoassays, as a prognostic marker for survival in AL amyloidosis. HLC measurements identified immunoparesis of at least one immunoglobulin (Ig) isotype in 145 (85%) patients; and severe immunoparesis (>=2 Ig isotypes suppressed by >50% below normal levels) in 29 (17%) patients. Median overall survival (OS) on intention to treat (ITT) analysis was 26.2 months. In the ITT cohort, dFLC >180 mg/l was associated with shorter OS (P = 0.05); whereas HLC immunoparesis was not prognostic. On a landmark analysis of 127 patients alive at 6 months, presenting dFLC was not prognostic for OS (P = 0.33) and severe HLC immunoparesis trended towards poorer survival (20.2 vs. 42.8 months; P = 0.09). In the subset of patients with cardiac involvement, severe HLC immunoparesis conferred very poor outcome (median OS 8.8 vs. 29.9 months, P = 0.007). In conclusion, severe HLC immunoparesis is an independent marker of long term poor prognosis in AL patients with cardiac involvement. The pathophysiological significance of this observation needs further study. PMID- 28990175 TI - Anaesthesia during endovascular stroke therapy - a strong or weak link in the treatment chain? PMID- 28990176 TI - Validation of subjective rating scales for assessment of surgical workspace during laparoscopy. AB - BACKGROUND: Recently, studies have focused on how to optimize laparoscopic surgical workspace by changes in intra-abdominal pressure, level of muscle relaxation or body position, typically evaluated by surgeons using subjective rating scales. We aimed to validate two rating scales by having surgeons assess surgical workspace in video sequences recorded during laparoscopic surgery. METHOD: Video sequences were obtained from laparoscopic procedures. Eight experienced surgeons assessed the video sequences on a categorical 5-point scale and a numerical 10-point rating scale. Intraclass correlations coefficients (ICC) and 95% confidence intervals (CI) were calculated for intra- and inter-rater reliability. RESULTS: The 5-point rating scale had an intra-rater ICC of 0.76 (0.69; 0.83) and an inter-rater ICC of 0.57 (0.45; 0.68), corresponding to excellent and fair reliability, respectively. The 10-point scale had an intra rater ICC of 0.86 (0.82; 0.89) and an inter-rater ICC of 0.54 (0.39; 0.68), corresponding to excellent and fair as well. All surgeons used the full range of the 5-point scale, but only one surgeon used the full range of the 10-point scale. CONCLUSION: In conclusion, both scales showed excellent intra-rater and fair inter-rater reliability for assessing surgical workspace in laparoscopy. The 5-point surgical rating scale had all categories employed by all surgeons. PMID- 28990177 TI - Reply to "Does use of perioperative COX-2 inhibitors really increase risk of acute kidney injury?" PMID- 28990178 TI - Intensive care admissions due to poisoning. AB - BACKGROUND: Poisoning represents a significant part of admissions to intensive care units. The aim of this nationwide study was to describe recent national quality register data of demographics and mortality for these patients. METHOD: A retrospective national observational study including all patients over 19 years admitted to an ICU in Sweden, between 1 January 2010 and 31 December 2011, with an ICD-10 code for poisoning. The data were collected from three national registers (The Swedish Intensive Care Register, The National Patient Register, and The Cause of Death Register). RESULTS: The incidence of ICU-treated poisonings was 43/100,000. Twenty-one per cent (n = 8155) of all poisoned patients seeking medical care were admitted to the ICU. Their median age was 38 years (q1-q3: 26-51), as many men as women and 46.5% (n = 3790) had a previous registered poisoning. A mix of different substances was the most common type of suspected poisoning (29.7%, n = 2424). The in-hospital mortality was 1.9% and was correlated to invasive mechanical ventilation (OR 6.91 CI 95% 4.59-10.42), age > 40 (OR 4.54 CI 95% 2.86-7.21) and no previous hospitalisation for poisoning (OR 3.23 CI 95% 2.06-5.07). For 78.3% (n = 119) of the deceased patients, the fatal poisoning was their first diagnosed poisoning. The 30-day mortality was 2.7%, a majority died from poisoning (P < 0.01). CONCLUSION: In Sweden, patients treated in the ICU due to poisoning represent a fifth of all poisoned patients seeking medical care. Older men with no previous poisoning were considered a high-risk group. PMID- 28990179 TI - Therapeutic bronchoscopy vs. standard of care in acute respiratory failure: a systematic review. AB - BACKGROUND: We aimed to assess patient-important benefits and harms of therapeutic bronchoscopy vs. standard of care (no bronchoscopy) in critically ill patients with acute respiratory failure (ARF). METHODS: We conducted a systematic review with meta-analysis and trial sequential analysis (TSA) according to the Cochrane Handbook and GRADE methodology, including a predefined protocol (PROSPERO no. CRD42016046235). We included randomized clinical trials (RCTs) comparing therapeutic bronchoscopy to standard of care in critically ill patients with ARF. Two reviewers independently assessed trials for inclusion, extracted data and assessed risk of bias. Risk ratios (RR) with 95% confidence intervals (CI) were estimated by conventional meta-analysis. The risk of random errors was assessed by TSA. Exclusively patient-important outcomes were evaluated. RESULTS: We included five trials (n = 212); all were judged as having high risk of bias. There was no difference in all-cause mortality between therapeutic bronchoscopy and standard of care (TSA adjusted RR 0.39; 95% CI 0.14 to 1.07; I2 0%), and only 3% of the required information size had been accrued. There was no difference in ICU length of stay. A shorter duration of mechanical ventilation was suggested by conventional meta-analysis, however TSA highlighted that only 42% of the required information size had been accrued, indicating high risk of random errors. No trials reported data on adverse events, hospital length of stay, quality of life or performance status. CONCLUSIONS: The quantity and quality of evidence supporting therapeutic bronchoscopy in critically ill patients with ARF is very low with no firm evidence for benefit or harm. PMID- 28990180 TI - What is the real incidence of Takotsubo syndrome in intensive care units? PMID- 28990181 TI - Long-term impairment attributable to congenital cytomegalovirus infection: a retrospective cohort study. AB - AIM: This study aimed to estimate long-term impairment attributable to congenital cytomegalovirus infection (cCMV). METHOD: This nationwide cohort study retrospectively assessed cCMV in children born in 2008 in the Netherlands, testing 31 484 stored neonatal dried blood spots. Extensive medical data of cCMV positive children (n=133) and matched cCMV-negative comparison children (n=274) up to 6 years of age were analysed. RESULTS: Moderate to severe long-term impairment was diagnosed in 24.8% (33 out of 133) of all cCMV-positive children (53.8% in symptomatic, 17.8% in asymptomatic), compared with 12.0% (33 out of 274) of cCMV-negative children. Sensorineural hearing loss was seen only in five cCMV-positive children (3.8%). Developmental delays were diagnosed more often in cCMV-positive children than cCMV-negative children: motor (12.0% vs 1.5%), cognitive (6.0% vs 1.1%), and speech-language (16.5% vs 7.3%). Long-term impairment in multiple domains was more frequent in symptomatic (19.2%) and asymptomatic (8.4%) cCMV-positive children than cCMV-negative children (1.8%). INTERPRETATION: Children with cCMV were twice as likely to have long-term impairment up to the age of 6 years, especially developmental delays and sensorineural hearing loss, than cCMV-negative comparison children, with a risk difference of 12.8%. These insights into the risk of cCMV-associated impairment can help optimize care and stimulate preventive measures. WHAT THIS PAPER ADDS: Congenital cytomegalovirus infection (cCMV) leads to impairment in 25% of cases. Fifty per cent of children with cCMV symptoms at birth have long-term impairment. The risk difference of moderate to severe long-term impairment between children with and without cCMV is 13%, attributable to cCMV. cCMV leads to motor, cognitive, and speech-language developmental delay in children. PMID- 28990182 TI - Effect of Chronic Kidney Disease on Nonrenal Elimination Pathways: A Systematic Assessment of CYP1A2, CYP2C8, CYP2C9, CYP2C19, and OATP. AB - Our recent studies have shown that chronic kidney disease (CKD) affects the pharmacokinetics (PKs) of cytochrome P450 (CYP)2D6-metabolized drugs, whereas effects were less evident on CYP3A4/5. Therefore, the effect of CKD on the disposition of CYP1A2-metabolized, CYP2C8-metabolized, CYP2C9-metabolized, CYP2C19-metabolized, and organic anion-transporting polypeptide (OATP) transported drugs was investigated. We identified dedicated CKD studies with 6, 5, 6, 4, and 12 "model" substrates for CYP1A2, CYP2C8, CYP2C9, CYP2C19, and OATP, respectively. Our analyses suggest that clearance of OATP substrates decreases as kidney function declines. Similar trends were seen for CYP2C8; but overlap between some CYP2C8 and OATP substrates highlights that their interplay needs further investigation. In contrast, the effect of CKD on CYP1A2, CYP2C9, and CYP2C19 was variable and modest compared to CYP2C8 and OATP. This improved understanding of elimination-pathway-dependency in CKD is important to inform the need and conduct of PK studies in these patients for nonrenally eliminated drugs. PMID- 28990184 TI - Corrigendum. PMID- 28990183 TI - Array CGH analysis reveals deletion of chromosome 22q11 in CLL with normal karyotype and no fish alterations. PMID- 28990186 TI - Molecular mechanisms underlying Grateloupia imbricata (Rhodophyta) carposporogenesis induced by methyl jasmonate. AB - When applied in vitro, methyl jasmonate is sensed by the red seaweed Grateloupia imbricate, substantially and visually affecting its carposporogenesis. However, although there is some understanding of the morphological changes induced by methyl jasmonate in vitro, little is known about the genes that are involved in red seaweed carposporogenesis and how their protein products act. For the work reported herein, the expression of genes in red seaweed that encode enzymes involved in the synthesis of methyl jasmonate (jasmonic acid carboxyl methyl transferase and a putative methyl transferase) was monitored. Additionally the genes involved in oxidation (cytochrome P450 and WD40), jasmonate synthesis, signal transduction, and regulation of reactive oxygen species (MYB), and reproduction (ornithine decarboxylase) were monitored. To determine when or if the aforementioned genes were expressed during cystocarp development, fertilized and fertile thalli were exposed to methyl jasmonate and gene expression was measured after 24 and 48 h. The results showed that methyl jasmonate promoted differential gene expression in fertilized thalli by 24 h and upregulated expression of the ornithine decarboxylase gene only by 48 h in fertile thalli (0.75 +/- 003 copies . MUL-1 at 24 h vs. 1.11 +/- 0.04 copies . MUL-1 at 48 h). We conclude that Ornithine decarboxylase expression involves methyl jasmonate signaling as well as development and maturation of cystocarps. PMID- 28990187 TI - Case-control study of shock index among women who did and did not receive blood transfusions due to postpartum hemorrhage. AB - OBJECTIVE: To compare shock index (SI) values between women who required blood transfusion due to postpartum hemorrhage (PPH) and women who did not. METHODS: In a case-control study, clinical data were assessed from the medical records of women requiring blood transfusion for PPH at a center in Brazil between 2012 and 2015 (n=105). A control group was randomly selected from women who did not receive blood transfusion (n=129). RESULTS: Compared with women who did not receive a transfusion after delivery, women who did receive one had significantly higher SI values 10 minutes after delivery (0.81 +/- 0.27 vs 0.72 +/- 0.16; P=0.012), at 30 minutes (0.83 +/- 0.26 vs 0.71 +/- 0.15; P<0.001), and at 2 hours (0.84 +/- 0.27 vs 0.70 +/- 0.14; P=0.032). For vaginal deliveries, SI values were significantly different at 30 minutes (0.88 +/- 0.26 vs 0.71 +/- 0.14; P<0.001) and 2 hours (0.90 +/- 0.23 vs 0.72 +/- 0.14; P=0.001). No significant differences were found for cesarean delivery. CONCLUSION: The SI might be useful to identify early vital sign changes due to PPH. Increased SI values were associated with need for transfusion in vaginal deliveries. PMID- 28990188 TI - A population-based study of the effect of pregnancy history on risk of stillbirth. AB - OBJECTIVE: To examine the effect of pregnancy history on the risk of stillbirth. METHODS: In a population-based cross-sectional study, data were reviewed from all women aged at least 20 years with singleton pregnancies in Finland between 2000 and 2010. The primary outcome-stillbirth-was defined as fetal death after 22 gestational weeks or death of a fetus weighing at least 500 g. RESULTS: Among 604 047 singleton pregnancies, the prevalence of stillbirth was 3.17 per 1000 deliveries. Prevalence was lowest for multiparous women without previous pregnancy loss after adjusting for major pregnancy complications associated with stillbirth (placenta previa, placental abruption, and pre-eclampsia) and other confounders. Relative to these women, stillbirth prevalence was higher among multiparous women with previous spontaneous abortion and/or stillbirth (adjusted odds ratio [aOR] 1.20, 95% confidence interval [CI] 1.05-1.36), nulliparous women with no previous pregnancy loss (aOR 1.23, 95% CI 1.10-1.38), and nulliparous women with prior spontaneous abortion (aOR 1.43, 95% CI 1.18-1.74). CONCLUSION: Previous pregnancy loss was found to be an independent risk factor for stillbirth, irrespective of the number of prior deliveries. PMID- 28990185 TI - Postaxial limb hypoplasia (PALH): the classification, clinical features, and related developmental biology. AB - Postaxial limb hypoplasia (PALH) is a group of nonhereditary diseases with congenital lower limb deficiency affecting the fibular ray, including fibular hemimelia, proximal femoral focal deficiency, and tarsal coalition. The etiology and the developmental biology of the anomaly are still not fully understood. Here, we review the previous classification systems, present the clinical features, and discuss the developmental biology of PALH. PMID- 28990189 TI - Cell wall physicochemical properties determine the thallus biomineralization pattern of Padina gymnospora (Phaeophyceae). AB - Approximately half of the Padina (Dictyotales, Phaeophyceae) species mineralize aragonite needles over the adaxial thallus surface, where mineral bands are interspersed with nonmineralized regions along the thallus from the apical to basal end. However, this calcification pattern and the related algal properties are not well understood. Therefore, this work was performed to elucidate a potential role of cell walls in the inhibition/induction of mineralization in the brown alga Padina gymnospora. In a comparison of specific thallus regions, differences were identified in the cellulose distribution, microfibrils arrangement and thickness, distribution and abundance of phenolic substances, and physical differences among the surfaces of the thallus (deformation, adhesion, topography, and nano-rugosity). In vitro mineralization assays indicated that phenolic substances are strong modulators of calcium carbonate crystals growth. In addition, de novo mineralization assays over cell wall surfaces that were used as templates, even without cellular activity, indicated that the cell wall remains a key factor in the induction/inhibition of mineralization. Overall, the current findings indicate a strong correlation between the physico-chemical and structural properties of the cell wall and the alternation pattern of the mineralization bands over the thallus of P. gymnospora. PMID- 28990190 TI - A randomized waitlist control community study of Social Cognition and Interaction Training for people with schizophrenia. AB - OBJECTIVE: Social Cognition and Interaction Training (SCIT) has demonstrated effectiveness in improving social cognition and functioning of people with schizophrenia. This pilot study examines the acceptability, feasibility, and effectiveness of SCIT with individuals who have schizophrenia-spectrum disorders and are receiving care through a public mental health service. METHOD: In a pragmatic randomized waitlist controlled trial, 36 participants (aged 19-55 years) with a schizophrenia spectrum disorder were randomly allocated to SCIT or treatment as usual (TAU). Measures of theory of mind, emotion perception, attributional bias, social skills, quality of life, life skills, depression, anxiety, and stress were administered pre- and post-intervention with follow-up conducted 4 months later. All wait-list controls subsequently received the intervention and a secondary within-group analysis was conducted including these participants. RESULTS: While no significant differences were found between groups on any outcomes, there was strong engagement with the SCIT intervention. Of the 21 participants in the intervention group, the completion rate was 85.71% with a median attendance rate of 17 sessions. Within subject analyses of SCIT participants over time showed significant improvements in quality of life, emotion recognition, social skills, and a trend towards better life skills from pre- to post-intervention. These gains were sustained at the 4-month follow-up time. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Although this study showed limited benefits in outcomes associated with SCIT compared with TAU, it demonstrated the acceptability of SCIT to participants in a real world public health setting shown by high retention, attendance, and positive feedback. This pilot shows SCIT can be implemented in routine clinical practice and lays the foundation for a larger pragmatic study. PRACTITIONER POINTS: SCIT can be implemented successfully in a real-world community mental health setting. SCIT had high levels of acceptability to these participants. Limitations The small sample size meant there was insufficient power to detect differences between groups on outcome measures. The study did not include measures of psychiatric symptoms or neuropsychological functioning which may have influenced participants' capacity to benefit from SCIT. PMID- 28990192 TI - Nonaqueous capillary electrophoresis mass spectrometry method for determining highly hydrophobic peptides. AB - A nonaqueous capillary electrophoresis mass spectrometry (NACE-MS) method was developed to separate and determine highly hydrophobic temporin peptides. The nonaqueous background electrolyte solution was a mixture of 20% acetonitrile, 78% methanol and 2% formic acid, with 20 mM ammonium formate. The separation of six peptides was completed within 12 min. The CE system was connected to a triple quadrupole mass spectrometer operating in MRM mode using a chemical modifier solution of 2 mM ammonium formate in ethanol with the flow through microvial interface. The mass spectrometer offered a second dimension of separation for peptides having identical migration times but different structures. The new method represents the first system capable of reliably determining hydrophobic peptides without using reversed phase liquid chromatography mass spectrometry. PMID- 28990191 TI - Chemical warfare agent simulants for human volunteer trials of emergency decontamination: A systematic review. AB - Incidents involving the release of chemical agents can pose significant risks to public health. In such an event, emergency decontamination of affected casualties may need to be undertaken to reduce injury and possible loss of life. To ensure these methods are effective, human volunteer trials (HVTs) of decontamination protocols, using simulant contaminants, have been conducted. Simulants must be used to mimic the physicochemical properties of more harmful chemicals, while remaining non-toxic at the dose applied. This review focuses on studies that employed chemical warfare agent simulants in decontamination contexts, to identify those simulants most suitable for use in HVTs of emergency decontamination. Twenty-two simulants were identified, of which 17 were determined unsuitable for use in HVTs. The remaining simulants (n = 5) were further scrutinized for potential suitability according to toxicity, physicochemical properties and similarities to their equivalent toxic counterparts. Three suitable simulants, for use in HVTs were identified; methyl salicylate (simulant for sulphur mustard), diethyl malonate (simulant for soman) and malathion (simulant for VX or toxic industrial chemicals). All have been safely used in previous HVTs, and have a range of physicochemical properties that would allow useful inference to more toxic chemicals when employed in future studies of emergency decontamination systems. PMID- 28990193 TI - Antimicrobial peptides as a possible interlink between periodontal diseases and its risk factors: A systematic review. AB - Antimicrobial peptides (AMPs) play a critical role in controlling innate and acquired immune responses. Local dysregulation of AMP is implicated in the pathogenesis of periodontal diseases as a response to periodontal pathogen challenge. Changes in AMP expression also characterize tobacco smoking, diabetes mellitus, obesity and rheumatoid arthritis, which are established risk factors of periodontal diseases, suggesting AMP may act as putative mechanistic links between these. The aim was to evaluate and summarize critically the current evidence pertaining to interrelationships between AMPs, periodontal diseases and selected periodontal disease risk factors. General and theme specific keywords were used to search the PUBMED database for studies relevant to AMP, periodontal diseases, smoking, diabetes mellitus, obesity and rheumatoid arthritis and critically reviewed. A total of 131 abstracts and 119 full text articles were screened for relevance; 13 studies were selected for inclusion after critical review. Local AMP dysregulation characteristic to periodontal diseases appears to occur within a broader landscape of complex systemic immune perturbations independently induced by smoking, metabolic and rheumatoid disease. The nature of these interactions and mechanistic pathways involved are inadequately understood. AMPs could be possible mechanistic interlinks between periodontal diseases and its risk factors. However, such evidence is very limited and more in vivo and in vitro studies are necessary to clarify the nature of such relationships. A greater understanding of AMPs as shared mediators is essential for unraveling their value as therapeutic or biomarker candidates. PMID- 28990194 TI - Relaxation of tyrosine pathway regulation underlies the evolution of betalain pigmentation in Caryophyllales. AB - Diverse natural products are synthesized in plants by specialized metabolic enzymes, which are often lineage-specific and derived from gene duplication followed by functional divergence. However, little is known about the contribution of primary metabolism to the evolution of specialized metabolic pathways. Betalain pigments, uniquely found in the plant order Caryophyllales, are synthesized from the aromatic amino acid l-tyrosine (Tyr) and replaced the otherwise ubiquitous phenylalanine-derived anthocyanins. This study combined biochemical, molecular and phylogenetic analyses, and uncovered coordinated evolution of Tyr and betalain biosynthetic pathways in Caryophyllales. We found that Beta vulgaris, which produces high concentrations of betalains, synthesizes Tyr via plastidic arogenate dehydrogenases (TyrAa /ADH) encoded by two ADH genes (BvADHalpha and BvADHbeta). Unlike BvADHbeta and other plant ADHs that are strongly inhibited by Tyr, BvADHalpha exhibited relaxed sensitivity to Tyr. Also, Tyr-insensitive BvADHalpha orthologs arose during the evolution of betalain pigmentation in the core Caryophyllales and later experienced relaxed selection and gene loss in lineages that reverted from betalain to anthocyanin pigmentation, such as Caryophyllaceae. These results suggest that relaxation of Tyr pathway regulation increased Tyr production and contributed to the evolution of betalain pigmentation, highlighting the significance of upstream primary metabolic regulation for the diversification of specialized plant metabolism. PMID- 28990196 TI - Concentration-controlled particle focusing in spiral elasto-inertial microfluidic devices. AB - Herein, we proposed a strategy for controlling the particle focusing position in Dean-coupled elasto-inertial flows via adjusting the polymer concentration of viscoelastic fluids. The physics behind the control strategy was then explored and discussed. At high polymer concentrations, the flowing particles could be single-line focused exactly at the channel centerline under the dominated elastic force. The center-line focusing in our spiral channel may employed as a potential pretreatment scheme for microflow cytometry detection. With further decreasing polymer concentrations, the particles would shift into the outer channel region under the comparable competition between inertial lift force, elastic force and Dean drag force. Finally, the observed position-shifting was successfully employed for particle concentration at a throughput much higher than most existing elasto-inertial microfluidics. PMID- 28990195 TI - Comparative analyses of industrial-scale human platelet lysate preparations. AB - BACKGROUND: Efforts are underway to eliminate fetal bovine serum from mammalian cell cultures for clinical use. An emerging, viable replacement option for fetal bovine serum is human platelet lysate (PL) as either a plasma-based or serum based product. STUDY DESIGN AND METHODS: Nine industrial-scale, serum-based PL manufacturing runs (i.e., lots) were performed, consisting of an average +/- standard deviation volume of 24.6 +/- 2.2 liters of pooled, platelet-rich plasma units that were obtained from apheresis donors. Manufactured lots were compared by evaluating various biochemical and functional test results. Comprehensive cytokine profiles of PL lots and product stability tests were performed. Global gene expression profiles of mesenchymal stromal cells (MSCs) cultured with plasma based or serum-based PL were compared to MSCs cultured with fetal bovine serum. RESULTS: Electrolyte and protein levels were relatively consistent among all serum-based PL lots, with only slight variations in glucose and calcium levels. All nine lots were as good as or better than fetal bovine serum in expanding MSCs. Serum-based PL stored at -80 degrees C remained stable over 2 years. Quantitative cytokine arrays showed similarities as well as dissimilarities in the proteins present in serum-based PL. Greater differences in MSC gene expression profiles were attributable to the starting cell source rather than with the use of either PL or fetal bovine serum as a culture supplement. CONCLUSION: Using a large-scale, standardized method, lot-to-lot variations were noted for industrial-scale preparations of serum-based PL products. However, all lots performed as well as or better than fetal bovine serum in supporting MSC growth. Together, these data indicate that off-the-shelf PL is a feasible substitute for fetal bovine serum in MSC cultures. PMID- 28990197 TI - Pollen tube growth and guidance: Occam's razor sharpened on a molecular arabinogalactan glycoprotein Rosetta Stone. AB - Occam's Razor suggests a new model of pollen tube tip growth based on a novel Hechtian oscillator that integrates a periplasmic arabinogalactan glycoprotein calcium (AGP-Ca2+ ) capacitor with tip-localized AGPs as the source of tip focussed cytosolic Ca2+ oscillations: Hechtian adhesion between the plasma membrane and the cell wall of the growing tip acts as a piconewton force transducer that couples the internal stress of a rapidly growing wall to the plasma membrane. Such Hechtian transduction opens stretch-activated Ca2+ channels and activates H+ -ATPase proton pump efflux that dissociates periplasmic AGP-Ca2+ resulting in a Ca2+ influx that activates exocytosis of wall precursors. Thus, a highly simplified pectic primary cell wall regulates its own synthesis by a Hechtian growth oscillator that regulates overall tip growth. By analogy with the three cryptic inscriptions of the classical Rosetta Stone, the Hechtian Hypothesis translates classical AGP function as a Ca2+ capacitor, pollen tube guide and wall plasticizer into a simple but widely applicable model of tip growth. Even wider ramifications of the Hechtian oscillator may implicate AGPs in osmosensing or gravisensing and other tropisms, leading us yet further towards the Holy Grail of plant growth. PMID- 28990198 TI - Exploring parkrun as a social context for collective health practices: running with and against the moral imperatives of health responsibilisation. AB - Critiques of public health policies to reduce physical inactivity have led to calls for practice-led research and the need to reduce the individualising effects of health promotion discourse. The purpose of this paper is to examine how parkrun - an increasingly popular, regular, community-based 5 km running event - comes to be understood as a 'health practice' that allows individuals to enact contemporary desires for better health in a collective social context. Taking a reflexive analytical approach, we use interview data from a geographically diverse sample of previously inactive parkrun participants (N = 19) to explore two themes. First, we argue that parkrun offers a space for 'collective bodywork' whereby participants simultaneously enact personal body projects while they also experience a sense of being 'all in this together' which works to ameliorate certain individualising effects of health responsibilisation. Second, we examine how parkrun figures as a health practice that makes available the subject position of the 'parkrunner'. In doing so, parkrun enables newly active participants to negotiate discourses of embodied risk to reconcile the otherwise paradoxical experience of being an 'unfit-runner'. Findings contribute to sociological understandings of health and illness through new insights into the relation between health practices and emerging physical cultures, such as parkrun. PMID- 28990199 TI - The epigenetic component of the brain response to electromagnetic stimulation in Parkinson's Disease patients: A literature overview. AB - Modulations of epigenetic machinery, namely DNA methylation pattern, histone modification, and non-coding RNAs expression, have been recently included among the key determinants contributing to Parkinson's Disease (PD) aetiopathogenesis and response to therapy. Along this line of reasoning, a set of experimental findings are highlighting the epigenetic-based response to electromagnetic (EM) therapies used to alleviate PD symptomatology, mainly Deep Brain Stimulation (DBS) and Transcranial Magnetic Stimulation (TMS). Notwithstanding the proven efficacy of EM therapies, the precise molecular mechanisms underlying the brain response to these types of stimulations are still far from being elucidated. In this review we provide an overview of the epigenetic changes triggered by DBS and TMS in both PD patients and neurons from different experimental animal models. Furthermore, we also propose a critical overview of the exposure modalities currently applied, in order to evaluate the technical robustness and dosimetric control of the stimulation, which are key issues to be carefully assessed when new molecular findings emerge from experimental studies. Bioelectromagnetics. 39:3-14, 2018. (c) 2017 Wiley Periodicals, Inc. PMID- 28990200 TI - Reduced ferritin levels in individuals with non-O blood group: results from the Danish Blood Donor Study. AB - BACKGROUND: Genomewide association studies have reported alleles in the ABO locus to be associated with ferritin levels. These studies warrant the investigation of a possible association between the ABO blood group and ferritin levels. We aimed to explore if ABO blood group is associated with iron stores expressed as ferritin levels. STUDY DESIGN AND METHODS: Ferritin levels were measured at least once for 30,595 Danish Blood Donor Study participants. Linear regression analyses were performed with the ABO blood group as explanatory variable and adjusted for age, number of donations 3 years before the ferritin measurement, and time since latest donation. In addition, a subanalysis was performed on 15,280 individuals in which further adjustments for body mass index, smoking status, and C-reactive protein levels were possible. Furthermore, logistic regression analyses were performed to determine if ABO blood group was associated with a ferritin level of less than 15 ng/mL. RESULTS: Non-O blood group donors had lower ferritin levels than blood group O donors, regardless of sex. Accordingly, risk of ferritin level of less than 15 ng/mL was increased for individuals with non-O blood group compared with O blood group. In subanalyses similar associations were observed, albeit in women the association between blood group and risk of a ferritin level below 15 ng/mL was no longer significant. ABO blood group was not associated with red blood cell indices such as mean cell volume and mean cell hemoglobin content. CONCLUSION: Donors with non-O blood group have lower ferritin levels than donors with other blood groups. PMID- 28990201 TI - Correlation between plasma fibrinogen and FIBTEM thromboelastometry during liver transplantation: a comprehensive assessment. AB - BACKGROUND: Thromboelastometry may reduce red blood cell (RBC) transfusion in liver transplantation (LT). Fibrinogen concentration is a primary determinant of FIBTEM maximum clot firmness (MCF), but several factors could affect the correlation between FIBTEM MCF and fibrinogen values. We aimed to investigate (1) the concordance between fibrinogen level and FIBTEM MCF and (2) the association of fibrinogen level and FIBTEM MCF with RBC transfusion during LT. METHODS: A post hoc analysis of data from a randomized, multicentre, double-blind, saline/fibrinogen trial was used (NCT01539057). A total of 86 adult patients were included. RESULTS: The Lin concordance coefficient (LCC) between FIBTEM MCF and fibrinogen levels with the model formula 1.3679 + 0.05414* FIBTEM MCF was poor overall (LLC [95% CI]: 0.387 [0.340 to 0.432]) and moderate for the preperfusion period (LLC [95% CI]: 0.789 [0.747 to 0.824]), but very poor for the postreperfusion period (LLC [95% CI] 0.170 [0.105 to 0.233]). The model assessed for RBC transfusion for FIBTEM MCF showed an area under the curve of 0.788 [0.745 0.832]. Patients with FIBTEM MCF values <8 mm had a significantly higher likelihood of receiving RBC than patients with higher values. (OR [95% CI]: 2.08 [1.30-3.33], P = 0.002). FIBTEM MCF values over 10 mm do not appear to reduce the likelihood of RBC transfusion. CONCLUSION: FIBTEM MCF is not a good indicator of plasma fibrinogen values after graft reperfusion. FIBTEM MCF >8 mm during the LT procedure is associated with less RBC transfusion. FIBTEM MCF values over 10 mm could lead to unnecessary fibrinogen administration. PMID- 28990202 TI - Beneath the hairy look: the hidden reproductive diversity of the Gibsmithia hawaiiensis complex (Dumontiaceae, Rhodophyta). AB - The tropical alga previously recognized as Gibsmithia hawaiiensis (Dumontiaceae, Rhodophyta) was recently suggested to represent a complex of species distributed throughout the Indo-Pacific Ocean and characterized by a peculiar combination of hairy (pilose) gelatinous lobes growing on cartilaginous stalks. Phylogenetic reconstructions based on three genetic markers are presented here with the inclusion of new samples. Further diversity is reported within the complex, with nine lineages spread in four major phylogenetic groups. The threshold between intra- and interspecific relationships was assessed by species delimitation methods, which indicate the existence of 8-10 putative species in the complex. Two species belonging to the G. hawaiiensis complex are described here: Gibsmithia malayensis sp. nov. from the Coral Triangle and Gibsmithia indopacifica sp. nov., widely distributed in the Central and Eastern Indo Pacific. Morphological differences in the vegetative and reproductive structures of the newly described species are provided and compared to the previously described species of the complex. Additional lineages represent putative species, which await further investigation to clarify their taxonomic status. Gibsmithia hawaiiensis sensu stricto is confirmed to be endemic to the Hawaiian Islands, and Gibsmithia eilatensis is apparently confined to the Red Sea, with an expanded distribution in the region. New records of the G. hawaiiensis complex are reported from Egypt, Saudi Arabia, Indonesia, Philippines, and the Federated States of Micronesia, indicating that the complex is more broadly distributed than previously considered. The isolated position of Gibsmithia within the Dumontiaceae is corroborated by molecular data. PMID- 28990203 TI - Drug-induced immune hemolytic anemia associated with anti-vancomycin complicated by a paraben antibody. AB - BACKGROUND: Drug-induced immune hemolytic anemia (DIIHA) is rare, but potentially life-threatening. A high index of clinical suspicion is required for diagnosis, since the number of medications known to induce DIIHA continues to expand. Additionally, in vitro antibody reactivity against reagent additives has been reported, which may complicate test interpretation. CASE REPORT: A 61-year-old group A, D+ woman with a history of negative antibody detection tests developed hemolytic anemia on Postoperative Day 7 after repeat incision and drainage of a chronically infected right knee prosthesis. She was treated with multiple antibiotics in the postoperative period, including three cephalosporins and vancomycin intravenously as well as vancomycin and gentamicin-containing intraarticular cement spacers. STUDY DESIGN AND METHODS: A workup for possible DIIHA was performed. Testing was performed using vancomycin and cephalosporin antibiotics. Initially, gentamicin injection solution was used for testing, followed by testing with its component ingredients. RESULTS: A vancomycin antibody was detected and anemia resolved after vancomycin was discontinued. Reactivity was seen when gentamicin injection solution was used for testing, raising the possibility of a gentamicin antibody as well. However, testing with purified gentamicin as well as methylparaben and propylparaben demonstrated a paraben antibody that reacted with the paraben-containing gentamicin solution. The patient also demonstrated an anti-N. Neither the paraben antibody nor the anti-N appeared to cause in vivo hemolysis. CONCLUSION: This is the second reported case of DIIHA associated with anti-vancomycin. It is the fourth report describing a paraben antibody. PMID- 28990204 TI - Serial Evaluation of Endometrial Blood Flow for Prediction of Pregnancy Outcomes in Patients Who Underwent Controlled Ovarian Hyperstimulation and In Vitro Fertilization and Embryo Transfer. AB - OBJECTIVES: To investigate endometrial blood flow during the menstrual cycle in patients undergoing controlled ovarian hyperstimulation (COH), in vitro fertilization (IVF), and embryo transfer (ET) and prediction of pregnancy outcomes based on these characteristics. METHODS: Endometrial blood flow was measured in 35 patients undergoing COH and IVF-ET (nonpregnant [n = 15] and pregnant [n = 20]) by measuring the resistive index (RI) of the uterine radial artery using 2-dimensional Doppler ultrasonography. Measurements were obtained in 4 different phases of the menstrual cycle day: early follicular, midfollicular, preovulatory, and midluteal. RESULTS: The uterine radial artery RI during the early follicular phase was significantly lower in the pregnant group than in the nonpregnant group (mean +/- SD, 0.61 +/- 0.01 versus 0.66 +/- 0.01; P = .029). There was no significant difference between groups during the midfollicular, preovulatory, and midluteal phases (mean +/- SD, 0.60 +/- 0.02 versus 0.60 +/- 0.01; P = .84; 0.61 +/- 0.09 versus 0.57 +/- 0.01; P = .12; 0.54 +/- 0.01 versus 0.57 +/- 0.02; P = .32, respectively). There was a significant difference in endometrial blood flow between the pregnant and nonpregnant groups during each phase (P = .016). The difference in the changes of the uterine radial artery RI from the preovulatory to midluteal phase between the pregnant and non pregnant groups was significant (-0.002 +/- 0.03 versus 0.07 +/- 0.02; P = .038). CONCLUSIONS: Increased endometrial blood flow during the midluteal phase, compared to the preovulatory phase, may correlate with successful COH and IVF-ET. Additionally, sufficient blood flow at initiation of COH may affect COH and IVF ET results. PMID- 28990205 TI - Developing a protocol for normothermic ex-situ limb perfusion. AB - BACKGROUND: Ischemia time represents a significant limitation for successful extremity transplantation because of the rapid deterioration of ischemic muscle. Normothermic ex-situ preservation is an emergent method to prolong the organ viability following procurement, by replicating the physiologic conditions. The aim of this study was to develop an ex-situ normothermic limb perfusion system to preserve the viability and function of porcine limbs for 12 hours following procurement. METHODS: A total of 18 swine limbs were perfused. Thirteen limbs were used to develop the perfusion protocol. Five limbs were perfused according to the optimized protocol. These limbs were perfused at 39 degrees C for twelve hours using an oxygenated colloid solution containing red blood cells. Glucose and electrolytes were kept within physiologic range by partial perfusate exchange. Limb specific perfusion quality was assessed by muscle contractility upon electrical nerve stimulation, compartment pressure, creatine kinase (CK) and myoglobin concentrations, tissue oxygen saturation (near infrared spectroscopy), indocyanine green angiography, and infrared radiation by thermographic imaging. RESULTS: The last five limbs reached the 12 hours' perfusion target maintaining normal compartment pressure (16.4 +/- 8.20 mmHg), minimal weight increase (0.54 +/- 7.35%), and mean muscle temperature of 33.6 +/- 1.67 degrees C. Myoglobin and CK concentrations were 875 +/- 291.4 ng/mL, and 53344 +/- 14850.34 U/L, respectively, at the end of perfusion. Muscle contraction was present in all limbs until cessation of perfusion. Differences in uniformity and quality of distal perfusion were identified with thermography and angiography imaging at 12 hours of perfusion. CONCLUSIONS: Ex-situ normothermic limb perfusion preserves swine limb physiology and function for at least 12 hours. PMID- 28990207 TI - A review of bioanalytical quantitative methods for selected sphingosine 1 phosphate receptor modulators. AB - Sphingosine 1-phosphate (S1P1 ) modulators provide an emerging therapeutic approach for various autoimmune disorders such as multiple sclerosis and psoriasis. Fingolimod is the first approved orally active, selective and potent drug of this class. Other drugs belonging to this class include siponimod, ponesimod, ceralifimod, amiselimod, CS-0777 and GSK2018682. However, owing to the high protein binding, polarity and zwitter-ionic nature of the phosphate metabolite of parent drugs, it becomes challenging to optimize the extraction method for this class of compounds. Although, there are individual published bioanalytical methods for the analysis of selected S1P1 modulators to support preclinical and clinical drug development, no extensive review compiling all the bioanalytical methods for the important drugs in the class is available. Thus, we attempted to prepare a comprehensive review on various bioanalytical methods for selected S1P1 modulators which will provide all the relevant bioanalytical information as required by bioanalytical researchers. This review focuses on the various liquid chromatography with tandem mass spectrometry methods that have been used to quantify S1P1 modulators in various biological matrices. Extraction methods included liquid-liquid extraction, solid-phase extraction and one-step protein precipitation for extracting the analytes. This review captures key information regarding sample processing options and chromatographic/detection conditions. PMID- 28990208 TI - Effectiveness of terrestrial protected areas for conservation of lake fish communities. AB - Freshwater protected areas are rare even though freshwater ecosystems are among the most imperiled in the world. Conservation actions within terrestrial protected areas (TPAs) such as development or resource extraction regulations may spill over to benefit freshwater ecosystems within their boundaries. Using data from 175 lakes across Ontario, Canada, we compared common indicators of fish assemblage status (i.e., species richness, Shannon diversity index, catch per unit effort, and normalized-length size spectrum slopes) to evaluate whether TPAs benefit lake fish assemblages. Nearest neighbor cluster analysis was used to generate pairs of lakes: inside versus outside, inside versus bordering, and bordering versus outside TPAs based on lake characteristics. The diversity and abundance indicators did not differ significantly across comparisons, but normalized-length size spectrum slopes (NLSS) were significantly steeper in lakes outside parks. The latter indicated assemblage differences (greater abundances of small-bodied species) and less-efficient energy transfer through the trophic levels of assemblages outside parks. Although not significantly different, pollution- and turbidity-tolerant species were more abundant outside parks, whereas 3 of the 4 pollution-intolerant species were more abundant within parks. Twenty-one percent of the difference in slopes was related to higher total dissolved solids concentrations and angling pressure. Our results support the hypothesis that TPAs benefit lake fish assemblages and suggest that NLSS slopes are informative indicators for aquatic protected area evaluations because they represent compositional and functional aspects of communities. PMID- 28990206 TI - Child maltreatment and eating disorders among men and women in adulthood: Results from a nationally representative United States sample. AB - OBJECTIVE: Child maltreatment is associated with an increased likelihood of having mood disorders, anxiety disorders, post-traumatic stress disorder, substance use disorders, and personality disorders, but far less is known about eating disorders. The objective of the current study was to examine the associations between child maltreatment, including harsh physical punishment, physical abuse, sexual abuse, emotional abuse, emotional neglect, physical neglect, and exposure to intimate partner violence, and eating disorders in adulthood among men and women. METHOD: Data were from the National Epidemiologic Survey on Alcohol and Related Conditions wave 3 (NESARC-III) collected in 2012 2013. The sample was nationally representative of the United States adult population (N = 36,309). Lifetime eating disorders (anorexia nervosa [AN], bulimia nervosa [BN], and binge-eating disorder [BED]) were assessed using diagnostic and statistical manual of mental disorders, fifth edition (DSM-5) criteria and the alcohol use disorder and associated disabilities interview schedule-5 (AUDADIS-5). RESULTS: The prevalence of any lifetime eating disorder was 1.7% (0.8% among men and 2.7% among women). All child maltreatment types were associated with AN, BN, and BED with notable differences among men and women. Overall, the types of child maltreatment with the strongest relationships with any eating disorder were sexual abuse and physical neglect among men and sexual abuse and emotional abuse among women. DISCUSSION: Clinicians should be mindful that child maltreatment experiences are associated with increased odds of eating disorders including AN, BED, and BN. Such relationships are significant among men and women although notable gender differences in these relationships exist. Abstract word count = 248. PMID- 28990209 TI - Sensitivity analysis for publication bias in meta-analysis of diagnostic studies for a continuous biomarker. AB - Publication bias is one of the most important issues in meta-analysis. For standard meta-analyses to examine intervention effects, the funnel plot and the trim-and-fill method are simple and widely used techniques for assessing and adjusting for the influence of publication bias, respectively. However, their use may be subjective and can then produce misleading insights. To make a more objective inference for publication bias, various sensitivity analysis methods have been proposed, including the Copas selection model. For meta-analysis of diagnostic studies evaluating a continuous biomarker, the summary receiver operating characteristic (sROC) curve is a very useful method in the presence of heterogeneous cutoff values. To our best knowledge, no methods are available for evaluation of influence of publication bias on estimation of the sROC curve. In this paper, we introduce a Copas-type selection model for meta-analysis of diagnostic studies and propose a sensitivity analysis method for publication bias. Our method enables us to assess the influence of publication bias on the estimation of the sROC curve and then judge whether the result of the meta analysis is sufficiently confident or should be interpreted with much caution. We illustrate our proposed method with real data. PMID- 28990210 TI - The impact of practice guidelines on opioid utilization for injured workers. AB - BACKGROUND: Opioid use is rising in the US and may cause special problems in workers compensation cases, including addiction and preventing a return to work after an injury. OBJECTIVE: This study evaluates a physician-level intervention to curb opioid usage. An insurer identified patients with out-of-guideline opioid utilization and called the prescribing physician to discuss the patient's treatment protocol. RESEARCH DESIGN: This study uses a differences-in-differences study design with a propensity-score-matched control group. Medical and pharmaceutical claims data from 2005 to 2011 were used for analyses. RESULTS: Following the intervention, the use of opioids increased for the intervention group and there is little impact on medical spending. CONCLUSIONS: Counseling physicians about patients with high opioid utilization may focus more attention on their care, but did not impact short-term outcomes. More robust interventions may be needed to manage opioid use. PERSPECTIVE: While the increasing use of opioids is of growing concern around the world, curbing the utilization of these powerfully addictive narcotics has proved elusive. This study examines a prescribing guidelines intervention designed to reduce the prescription of opioids following an injury. The study finds that there was little change in the opioid utilization after the intervention, suggesting interventions along other parts of the prescribing pathway may be needed. PMID- 28990213 TI - The complex relationship among arteriovenous access, heart, and circulation. AB - There are currently near 400 000 patients on hemodialysis in the United States. More than 50% of those treated by chronic hemodialysis die because of a cardiovascular (CV) event. The majority of these patients have functional arteriovenous fistulas (AVFs). AVFs have an adverse effect on cardiac function, but their exact contribution to CV morbidity is not clear. It has long been known that a vascular access with an inappropriately high-flow rate may cause high output heart failure. Paradoxically, there may be hemodynamic and cardiopulmonary benefits conferred by AVF particularly in severe chronic obstructive pulmonary disease. While Brescia-Cimino's basic idea of the AVF has saved millions of lives, we would like to stress that there are dangers from their often high blood flow rates, which unfortunately have proved difficult to evaluate. PMID- 28990211 TI - Translation research in occupational safety and health: A proposed framework. AB - Translation research in occupational safety and health is the application of scientific investigative approaches to study how the outputs of basic and applied research can be effectively translated into practice and have an impact. This includes the study of the ways in which useful knowledge and interventions are disseminated, adopted, implemented, and institutionalized. In this paper, a 4 stage framework (Development, Testing, Institutionalization, and Evaluation) is presented. Translation research can be used to enhance the use and impact of occupational safety and health knowledge and interventions to protect workers. This type of research has not received much attention in the occupational safety and health field. However, in contemporary society, it is critical to know how to make an impact with the findings and outputs of basic and applied research. This paper provides a novel framework for consideration of how to advance and prioritize translation research for occupational safety and health. PMID- 28990212 TI - Normal Development of the Corpus Callosum and Evolution of Corpus Callosum Sexual Dimorphism in Infancy. AB - OBJECTIVES: The aim of this study was to establish reference ranges for the corpus callosum in infancy and to clarify how sexual dimorphism evolves between the fetal stage and infancy. METHODS: Normal sonograms from cerebral ultrasonographic examinations of 1- to 6-month-old healthy full-term infants were selected. The length and thickness of the corpus callosum were determined, and the effect of sex on these values was analyzed. Studies on corpus callosum sexual dimorphism were reviewed. RESULTS: In total, sonograms from 236 1- to 6-month-old infants (120 male and 116 female) were collected, and the typical values (5th 95th percentiles) of the corpus callosum were determined for each group. During the first 2 months, with and without brain size adjustment, the corpus callosum in female infants was significantly thicker than that in male infants (mean thickness +/- SD: 1 month, male infant, 1.8 +/- 0.3 mm; female infant, 2.1 +/- 0.3 mm; P = .005; 2 months, male infant, 1.8 +/- 0.2 mm; female infant, 2.0 +/- 0.3 mm; P = .002). The corpus callosum thickness of male and female infants had no significant differences after 2 months of age. Sexual dimorphism was not detected in corpus callosum length. CONCLUSIONS: Our study provides reference data on typical corpus callosum development in infants. In the fetal period and early infancy, the corpus callosum in female infants is thicker than that in male infants. From 3 months onward, the corpus callosum sexual dimorphism becomes insignificant throughout childhood. The evolvement of corpus callosum sexual dimorphism suggests that maternal factors may influence brain development. PMID- 28990214 TI - Reply. PMID- 28990215 TI - Ultrasonic Perfluorohexane-Loaded Monocyte Imaging: Toward a Minimally Invasive Technique for Selective Detection of Liver Inflammation in Fatty Liver Disease. AB - OBJECTIVES: To investigate the utility of ultrasonic (US) perfluorohexane (PFH) loaded monocyte imaging for detection of liver inflammation in fatty liver disease. METHODS: C57Bl6 mice were injected intraperitoneally with tumor necrosis factor alpha and assessed by US PFH-loaded monocyte imaging 3 hours later. Echogenic monocytes were injected intravenously, leading to a transient increase in liver tissue intensity on a US perfusion scan. The contrast wash-out time constant was hypothesized to reflect the degree of inflammation. Next, we evaluated US PFH-loaded monocyte imaging in Ldlr-/- mice fed a 1-week high fat/high-cholesterol diet as model for early developing nonalcoholic steatohepatitis. Adjunct analyses included tissue markers of liver inflammation. RESULTS: Tumor necrosis factor alpha-injected mice showed a reduced wash-out time constant (mean +/- SEM, 0.013 +/- 0.003; n = 8) compared to controls (0.054 +/- 0.009; n = 7; P = .0006), indicative of increased inflammatory adhesion molecule expression on the endothelium. The Ldlr-/- mice fed the high-fat/high-cholesterol diet showed liver inflammation, as reflected by increased (3- to 4-fold) infiltration of inflammatory cells and increased (3- to 4-fold) gene expression of tumor necrosis factor alpha, integrin alphaM, intracellular adhesion molecule, and vascular cell adhesion molecule. However, in these mice, no difference was detected in the wash-out time constant as assessed by US PFH-loaded monocyte imaging (high-fat/high-cholesterol, 0.050 +/- 0.017; n = 5; chow, 0.048 +/- 0.006; n = 6; P = .91). CONCLUSIONS: Our results indicate that US PFH-loaded monocyte imaging is able to detect vascularly expressed inflammatory adhesion molecules in the mouse liver on direct endothelial stimulation. However, in our mouse model of early developing nonalcoholic steatohepatitis, we did not detect inflammation by this method, which may suggest that the time-dependent relationship between parenchymal and endothelial inflammation remains a fundamental issue to be addressed. PMID- 28990216 TI - Left atrial volume changes are an early marker of end-organ damage in essential hypertension: A multidisciplinary approach to an old problem. AB - PURPOSE: Left atrial (LA) volume has been shown to be a predictor of adverse cardiovascular outcomes. The aim of this study was to evaluate the relation between LA phasic volumes and hypertensive end-organ damage (EOD), by using real time three-dimensional echocardiography (RT3DE) in patients with essential hypertension (HT). METHODS: The study included 95 essential hypertensive patients (60 +/- 10 years, 37 males). The patients were divided into three according to the presence of EOD, namely microalbuminuria and retinal vascular changes detected by direct ophthalmoscopy. The first group had no EOD. The second group (EOD+ group) had either microalbuminuria or retinal vascular changes while the third group (EOD++ group) had both renal and retinal damage. RESULTS: The three groups did not differ with regard to age, sex, or metabolic profile. In RT3DE measurements, there were significant differences in LA phasic volumes (LA maximal volume index, LA minimal volume index, LA pre-atrial contraction volume index, LA total stroke volume index, and LA active stroke volume index, P < .001) among the groups. Moreover, patients with more extended EOD had significantly worse LA reservoir and conduit functions. In the logistic regression analysis, the LA active stroke volume index was an independent predictor of EOD (82% sensitivity and 92% specificity, area under the curve = 0.96, P < .001). CONCLUSION: RT3DE measured LA phasic volumes and mechanical functions are associated with hypertensive EOD, which might serve as a surrogate endpoint for determining cardiovascular mortality and morbidity rates in patients with essential HT. PMID- 28990217 TI - Identification of three prophenoloxidase-activating factors (PPAFs) from an invasive beetle Octodonta nipae Maulik (Coleoptera: Chrysomelidae) and their roles in the prophenoloxidase activation. AB - A typical characteristic of the insect innate immune system is the activation of the serine protease cascade in the hemolymph. As being the terminal component of the extracellular serine protease cascade in the prophenoloxidase (proPO) activating system, proPO-activating factors (PPAFs) activated by the upstream cascade may generate active phenoloxidase, which then induces downstream melanization. In the present study, we reported three PPAFs from the nipa palm hispid beetle Octodonta nipae (Maulik) (designated as OnPPAF1, OnPPAF2, OnPPAF3). All three OnPPAFs contained a single clip domain at the amino-terminus followed by a trypsin-like serine protease domain at the carboxyl-terminus, except the Ser in the active sites of OnPPAF2 and OnPPAF3 was substituted with Gly. Transcript expression analysis revealed that all OnPPAFs were highly expressed in hemolymph, whereas OnPPAF2 showed an extremely low mRNA abundance compared with that of OnPPAF1 and OnPPAF3, and that the abundance of all three OnPPAFs was dramatically increased upon bacterial challenge. Knockdown of OnPPAF1 or OnPPAF3 resulted in a reduction of hemolymph phenoloxidase activity and an inhibition of hemolymph melanization, whereas the knockdown of OnPPAF2 did not affect the proPO cascade. Our work thus implies that the three OnPPAFs may have different functions and regulation during immune responses in O. nipae. PMID- 28990219 TI - Emergency Ultrasound: A Survey Study of Fellowship Graduate Characteristics and Career Paths. AB - OBJECTIVES: There are sparse data on the career pathways of graduates of emergency ultrasound fellowships. The authors sought to define the characteristics of graduates and their reported career paths after training through this survey study. METHODS: A 26-question anonymous survey was emailed to 597 graduates of 70 fellowships over a 4-week period. No incentives were provided for completion of the questionnaire. Descriptive statistics are reported. For qualitative data, open- and axial-coding methods were used. RESULTS: A total of 336 participants completed the study for a response rate of 56%. The average age of respondents was 36.4 years, and 58% were male. Most graduates had MD degrees (89%) or DO degrees (10%). Sixty percent of graduates attended a 3-year emergency medicine residency, and 29% attended a 4-year residency. Only 11% pursued additional fellowship training, most commonly pediatric emergency medicine (n = 14). After fellowship, 63% (95% confidence interval [CI], 62.9, 63.1) of graduates began working full-time in an academic setting, whereas 24% (95% CI, 23.9, 24.1) worked full-time in a community setting. Thirty-three percent (95% CI, 32.7, 33.3) took an immediate position as ultrasound division director, whereas 4% (95% CI, 3.7, 4.3) became fellowship directors and 3% (95% CI, 2.7, 3.3) became ultrasound medical student directors. Currently, 67% (95% CI, 66-68%) identify ultrasound as their leading academic focus. CONCLUSIONS: Although not all fellowship graduates pursue academic positions, most note the impact of fellowship on their career paths. Graduates hold a variety of leadership positions. Approximately two thirds still consider ultrasound as their academic focus. PMID- 28990218 TI - A polysaccharide from Dictyophora indusiata inhibits the immunosuppressive function of cancer-associated fibroblasts. AB - Reversing the function of cancer-associated fibroblasts (CAFs) may improve the efficacy of cancer therapy. Here, we isolated a novel polysaccharide from Dictyophora indusiata (ZSP4) and examined its effects on the function of prostate CAFs. The supernatant of prostate CAFs can stimulate the proliferation of immune cells and inhibit the growth of CD4+/CD8+ T cells. However, after ZSP4 stimulation, the functions of prostate CAFs were inhibited. The mechanism experiment shows that ZSP4 can stimulate prostate CAFs by down-regulating the expression of alpha-smooth muscle actin. Polysaccharides extracted from Dictyophora indusiata stimulate the proliferation of immune cells and reverse the immune-suppressive functions of prostate CAFs, shedding new light on the development of novel anticancer strategies. The endocrine therapy used to treat prostate cancer aims to eliminate androgenic activity from prostatic tissue; these therapies are painful and of poor therapeutic effect. In this study, we found that polysaccharides extracted from Dictyophora indusiata may affect the micro-environment of tumours and inhibit the growth of the tumours. Our results suggest that polysaccharides may modulate negative immune regulation and enhance antitumour immunity, which is important for clinical therapy. PMID- 28990220 TI - Low-dose basiliximab induction therapy in heart transplantation. AB - We prospectively studied efficacy and safety outcomes of two 10-mg doses of intravenous basiliximab on day 0 and day 4 for induction therapy in 17 consecutive de novo heart transplant recipients. By the 2-week assessment post transplant, there were no deaths, graft failures, or acute cellular rejections (ACRs) ISHLT grade >= 2R. By the 1-year assessment post-transplant, there were 1 (6%) infectious death, no graft failures, 2 (12%) grade 2R ACRs, 6 (35%) asymptomatic cytomegalovirus (CMV) infections, and 4 (25%) treated infections. Our study was the first to show that low-dose basiliximab induction in heart transplant resulted in favorable efficacy and safety outcomes. Additionally, calcineurin inhibitor (CNI) initiation in a low-risk population could be safely delayed using the strategy of modified low-dose postoperative basiliximab. This strategy also appears to allow subsequent early corticosteroid wean, although with the concomitant maintenance of higher CNI levels and higher dosing of mycophenolate. PMID- 28990221 TI - Growth performance of piglets during the first two weeks of lactation affects the development of the intestinal microbiota. AB - The aim of this study was to evaluate the effect of newborn piglet weight gain during the first 2 weeks of lactation on the luminal and mucosal microbiota of the ileum and colon. The microbiota from high-weight-gain (HWG) and low-weight gain (LWG) 2-week-old piglets was characterized by amplicon length heterogeneity PCR (LH-PCR) and compared using diversity indices and multivariate statistical analyses. At birth, LWG piglets weighted in average 0.26 kg less than HWG piglets (p = .002). The weight difference between LWG and HWG piglets increased with time and reached 2.1 kg after 16 days of lactation (p < .0001). Based on these growth performance differences, estimated colostrum and milk intake was greater in HWG than in LWG piglets (p < .0001). Analysis of the LH-PCR data of the microbiota using non-metric multidimensional scaling (NMS) and blocked multiresponse permutation procedure (MRBP) revealed that the microbiota of the HWG and LWG piglets tended to differ in ileal mucosa (p = .097) and differed in colonic lumen (p = .024). The microbiota of HWG piglets had higher levels of Bacteroidetes, Bacteroides and Ruminoccocaceae, and lower proportions of Actinobacillus porcinus and Lactobacillus amylovorus when compared with those of LWG piglets. As the weight gain of nursing piglets is highly correlated with the amount of ingested colostrum and milk, the results strongly suggest that colostrum and milk intake in the first 2 weeks of life influenced the development of the gut microbiota. PMID- 28990223 TI - The establishment of a Middle East Acne Advisory Board: a success story. PMID- 28990222 TI - Managing acne in the Middle East: consensus recommendations. AB - Acne has been estimated to affect the majority of people at some point in their life and is common in Middle Eastern countries. While acne is frequently perceived to be a self-limited disease of adolescence, there is an increasing population of adults with acne. Information about the management of acne in the Middle East is somewhat sparse; however, several studies have recently been conducted and will be discussed in this supplement. PMID- 28990224 TI - Evaluation of haematological, serum biochemical and histopathological parameters of growing rabbits fed Amaranthus dubius. AB - Amaranthus dubius is an alternative source of fibre and protein for the feed formulation for growing rabbits, although its effects on their health status are yet unknown. Therefore, this study aimed to evaluate the effects of three dietary levels (0, 160 and 320 g/kg) of A. dubius on haematological, serum biochemical and histopathological parameters of fattening rabbits. One hundred and thirteen New Zealand White rabbits were fed ad libitum from weaning (35 days) to slaughter (87 days). The health status of the animals was monitored, and mortality was recorded. Before slaughtering, 30 rabbits were randomly selected for haematological and serum biochemical analysis. During slaughter, 18 rabbits were randomly selected for histopathological study in heart, liver, lung and small intestine. The health status of rabbits was good, with no differences among treatments in mortality. Diet and sex did not affect the values of most haematological and serum biochemical parameters. Fibrinogen, glucose and high density lipoprotein values increased significantly from 0 to 320 g/kg A. dubius diets. The white blood cell count and glutamic oxaloacetic transaminase values decreased significantly from 0 to 320 g/kg A. dubius diets. The organs showed histologically well-structured tissues. However, in all experimental groups several samples with lesions were observed, always highly focalized in small tissue areas. The main lesions observed, probably related to conditions of thermal stress affecting the rabbits, were cholesterolosis (heart), steatosis (liver), inflammatory lymphoplasmacytic infiltrate (lung) and chronic inflammatory tissue damage (small intestine). In conclusion, the inclusion of up to 320 g/kg A. dubius in diet did not jeopardize the health status of growing rabbits. Therefore, A. dubius can become an alternative raw material for the formulation of feeds in tropical and subtropical countries where this plant is widespread. PMID- 28990225 TI - Feasibility of diaphragm pacing in patients after bilateral lung transplantation. AB - Recent animal studies and intraoperative studies in humans suggested that phrenic nerve stimulation could attenuate ventilator-induced diaphragm dysfunction. The purpose of the present study is to examine the safety and feasibility of diaphragm pacing during the weaning process after bilateral lung transplantation. Four patients, suffering from chronic pulmonary disease, were included, and diaphragm pacing was evaluated after lung transplantation. Implantation of electrodes at the end of the lung transplant procedure was possible in three of the four patients. In all implanted patients, stimulation of the diaphragm could trigger the ventilator. Implanted electrodes were completely removed by percutaneous retraction after up to 7 days of pacing. Adverse events related to pacing included occurrence of pain. Diaphragm pacing with temporary electrodes, inserted during surgery, is feasible and is able to trigger the ventilator in patients after bilateral lung transplantation. The use of intradiaphragmatic electrodes creates the additional opportunity to monitor the evolution of diaphragm electromyography during the postoperative weaning process. PMID- 28990226 TI - Milk fatty acid profile from cows fed with mixed rations and different access time to pastureland during early lactation. AB - Milk fatty acid (FA) profiles were determined in Holstein cows (n = 27) fed total mixed rations (TMR) ad libitum (G0) or diet composed by TMR (50% dry matter [DM] offered) plus grazing of pasture with 6 hr of access time to paddock in one session (G1) or 9 hr in two sessions (G2) at 45 days in milk (DIM). Moreover, milk FA was determined at 65 DIM when G0 cows turned out to G1 diet without adaptation period (Post-G0), G1 remained as controls. Milk FA was quantified using gas chromatography and mass spectrometry. Preformed FA at 45 DIM was greater (+27%) for G2 than G0 cows (p < .05). Stearic acid (C18:0) was 30% greater for G2 cows (p < .05). De novo FA was lowest for G2 cows (p < .05). Conjugated linoleic acid (CLA) did not differ (p < .12), while vaccenic acid (C18:1trans) was twofold greater for grazing treatments (p < .01). Linolenic acid [C18:3(n-3)] was greatest for G2 and lowest for G0 cows (p < .01). Omega 6 FA was greater for G0 than grazing cows, mainly due to linoleic acid [18:2cis(n-6); p < .05]. These results determined that n-6/n-3 ratio was almost threefold greater for G0 than grazing cows (p < .001). When diet of G0 cows changed to include pasture (Post-G0), preformed FA increased (p < .05), explained mainly by the increase (p < .05) of stearic (C18:0) and C18:1trans, while de novo FA tended to decrease (p < .1). Moreover, the amount of CLA and C18:3(n-3) tended to increase (p < .1) in Post-G0 cows. Offering 50% of dietary DM from pasture modified milk FA profile in early lactation potentially beneficial for human health. When TMR fed cows were turned out to 50% pasture, milk FA profile reflected dietary change without need of an adaptation period. PMID- 28990227 TI - Re Doping in 2D Transition Metal Dichalcogenides as a New Route to Tailor Structural Phases and Induced Magnetism. AB - Alloying in 2D results in the development of new, diverse, and versatile systems with prospects in bandgap engineering, catalysis, and energy storage. Tailoring structural phase transitions using alloying is a novel idea with implications in designing all 2D device architecture as the structural phases in 2D materials such as transition metal dichalcogenides are correlated with electronic phases. Here, this study develops a new growth strategy employing chemical vapor deposition to grow monolayer 2D alloys of Re-doped MoSe2 with show composition tunable structural phase variations. The compositions where the phase transition is observed agree well with the theoretical predictions for these 2D systems. It is also shown that in addition to the predicted new electronic phases, these systems also provide opportunities to study novel phenomena such as magnetism which broadens the range of their applications. PMID- 28990228 TI - Influence of outdoor rearing and oleic acid supplementation on lipid characteristics of muscle and adipose tissues from obese Alentejano pigs. AB - Data evaluating the effect of oleic-acid-enriched diets and outdoor rearing (with access to pasture) on the quality of Alentejano (AL) pork and fat are limited. The aim of this work was to study the effects of feeding low (LO) or high oleic acid (HO) diets to AL pigs reared in individual pens (IND) or outdoors (OUT) with access to pasture. Biceps femoris and dorsal subcutaneous fat (DSF) samples were collected to analyse chemical composition and lipids fatty acid (FA) profile. The expression of seven genes involved in lipogenesis, lipolysis and FA transport, as well as two transcription factors were also evaluated in the muscle. B. femoris and DSF presented lower lipid content in OUT-reared than in IND-reared pigs. Two genes involved in lipogenesis, ACACA and FASN, were under-expressed in B. femoris from OUT-reared pigs, while two involved in lipolysis, LPL and HSL were over expressed. HO diet also significantly reduced FASN expression. Both rearing system and diet affected the FA profile of tissues, particularly DSF. Overall, OUT-reared pigs presented lower n6 to n3 FA ratios in all tissues, and lower monounsaturated (MUFA) and higher polyunsaturated fatty acids (PUFA) content in DSF. When compared to LO-fed ones, HO-fed pigs presented higher oleic acid proportions in all tissues, and lower SFA, higher MUFA and PUFA levels, as well as lower saturation, atherogenic and thrombogenic indexes in DSF. This study shows that rearing system and oleic acid supplementation have complementary effects and influence the nutritional quality of pork and DSF. PMID- 28990229 TI - Association of single-nucleotide polymorphism of melanocortin gene with feed intake in rabbit (Oryctolagus cuniculus). AB - The aim of the study was to investigate the association of two parts of melanocortin gene (MC4R-1, MC4R-2) and feed intake for V-line rabbits. V-line rabbits were grouped into high and low daily feed intake during the period from 30 to 63 days of age in order to identify MC4R SNPs useful for association study with feed intake. DNA from blood samples of each group was extracted to amplify the MC4R gene. The purified PCR products were sequenced in those had the highest and lowest feed intake. Alignment of sequence data from each group revealed that there is a variation detected in MC4R-1 at nucleotide 35 (T-G) (sense mutation) and another variation was detected in MC4R-2 gene at nucleotide 19 (T-C) (sense mutation) for high feed intake rabbits. These sense mutations lead to transform some amino acids and cause a significant change of the MC4R function. The results of average daily feed intake (ADFI) indicated that group (1) had significantly higher feed intake than group (2) of V-line rabbits. The detected mutations and the analysis of daily feed intake means revealed a significant association between MC4R polymorphism and feed intake in rabbits. PMID- 28990230 TI - Response of in ovo administration of zinc on egg hatchability and immune response of commercial broiler chicken. AB - An experiment was conducted to determine the effect of in ovo administration of different forms of zinc with respect to hatchability and performance of commercial broiler chicken. In trial 1, the fertile eggs on day 18 were divided into six treatment groups: Group I as control without any supplementation of zinc, group II to IV were supplemented with 0.5 mg zinc per egg as zinc sulphate, zinc methionine or nano zinc, respectively, and Group V with nano zinc at 0.25 mg zinc per egg. Sixth group received 0.5 ml citric acid per egg as sham control. The results of the first trial indicated that in ovo administration of nano zinc at both levels and zinc methionine resulted in complete failure of hatchability. A second trial to validate the result of trial 1 consisted of Group I control (no administration). Group II and Group III were supplemented with zinc sulphate and zinc methionine, respectively, at 0.5 mg zinc per egg. Group IV and Group V were supplemented with nano zinc at 0.04 and 0.08 mg per egg. In the second trial, again there was a similar pattern for zinc sulphate and zinc methionine. Administration of Zn by nano form had around 80% hatchability on fertile eggs in comparison with the unadministered control eggs (92%). There was no difference (p > .05) in body weight gain, feed intake and FCR. No difference (p > .05) was observed between treatments for cell-mediated immune response and humoral immune response. Nano Zn-administered group showed a non-significant downregulation of MUC2 gene. It could be concluded that in ovo administration of higher levels of zinc has to be with caution for the developing embryo of commercial broiler chicken. PMID- 28990231 TI - IFI16 restoration in hepatocellular carcinoma induces tumour inhibition via activation of p53 signals and inflammasome. AB - OBJECTIVE: Interferon-inducible 16 (IFI16) is known to involve in p53-dependent tumour suppression and also the formation of inflammasome, which function, however, remains controversy during carcinogenesis as a pattern recognition receptor for tumour death-derived free DNA. In this study, we investigated the anti-tumour role of IFI16 in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Hepatocellular carcinoma tissues (n = 20) and corresponding non neoplastic tissues (n = 20) were collected to determine the expression of IFI16. After the transfection of pcDNA3.1-IFI16 into Huh7 and SMMC7721 cells in vitro, the influence of IFI16 overexpression on cell vitality, colony formation, apoptosis and migration were analysed. The role effect of IFI16 in vivo was further investigated. RESULTS: The expression of IFI16 was significantly decreased in tumour tissues and cell lines. Overexpression of IFI16 induced decrease of cell vitality, colony formation and increased apoptosis with impaired ability of migration. Mechanistically, IFI16 could activate p53 at Ser15 to up regulate the p21WAF1/CIP1 level to inhibit tumour growth and migration, which was restored by the p53 inhibitor Pifithrin-alpha (20 MUmol/L). Moreover, IFI16 induced tumour cell death promoted the recruitment of inflammasome complex to enhance tumour inhibition, but the caspase-1 inhibitor Ac-YVAD-CMK (50 MUmol/L) could suppress this process in HCC. The results in vivo indicated that restored expression of IFI16 in tumour cells effectively promote tumour regression, which could be partly abrogated by the inhibition of activation of p53 signals or induced inflammasome. CONCLUSION: IFI16 is a tumour suppressor in HCC via activation of p53 signals and inflammasome. PMID- 28990232 TI - Shape-Controlled Synthesis of Au-Polypyrrole Composites Using Poly(4 vinylpyridine) Brush Grafted on Graphene Oxide as a Reaction Chamber. AB - Controlling the shape of the conducting polymer-noble metal composites is a key factor in determining their properties and applications. In this paper, we demonstrate a novel strategy to fabricate Au-polypyrrole (PPy) composites with unusual morphology using poly(4-vinylpyridine) (P4VP) brush grafted on graphene oxide (GO) as a reaction chamber. When the GO/P4VP brush bearing AuCl4- ions is exposed to pyrrole vapor or directly immersed into pyrrole solution, novel Au-PPy nanotubules and flower-like Au mesoparticles-PPy composites are formed on the surface of GO/P4VP brush, respectively. The application of the as-prepared GO/P4VP/Au-PPy composites in catalysis and surface-enhanced Raman scattering (SERS) are investigated. The relevant results exhibit that the GO/P4VP/Au-PPy nanotubules can act as an efficient catalyst for reduction of 4-nitrophenol, and the GO/P4VP/flower-like Au mesoparticles-PPy composites can be used as a sensor platform for the detection of organic molecules by SERS. PMID- 28990233 TI - Molecular dynamics investigation of stereoselective inhibition mechanism of HIF 2alpha/ARNT heterodimer. AB - Hypoxia-inducible factors (HIFs) are heterodimeric transcription factors related with the onset and progression of solid tumors. Studies demonstrated a class of tetrazole containing chiral inhibitors could stereoselectively disrupt the HIF-2 dimerization and reduce the target gene expression. However, the dynamical features and structural motifs of the HIF-2 heterodimer caused by the binding of enantiomers have not been rationalized at the atomistic level. In this work, molecular dynamics (MD) simulations combined with adaptive steered MD (ASMD) simulations were used to investigate stereoselective interrupting mechanism of HIF-2. Our results decipher that the binding of ligand A (S, R)-24 begets the significant conformation changes of beta-sheets and interrupts the HIF 2alpha/ARNT heterodimerization, which may be attributed to the disruption of the hydrogen bond and salt bridge interactions formed by the 4 foremost residues (Asp240, Arg247, Glu362, and Arg366) and the destruction of hydrophobic interactions on the binding interface. By contrast, the binding of ligand B (R, S)-24 does not disrupt protein dimerization and causes the motion of Falpha helix in HIF-2alpha PAS-B domain to further change the major tunnel for ligand ingress and engress. The present work provides important molecular-level insight into the effect of the binding enantiomers on HIF-2 heterodimerization and bridges the gap between theory and the experimental results, which may conduce to develop highly potent antagonists for intervening the HIF-2-driven tumors. PMID- 28990234 TI - Safety of Atrovent(r) CFC-free inhaler: respiratory events reported from an observational cohort study in England. AB - OBJECTIVES: The aim of the study was to identify any unexpected clinical events associated with starting the new CFC-free formulation of Atrovent(r) MDI in general practice in England. METHODS: An active surveillance cohort study was conducted with a focus on selected clinical events, including respiratory symptoms, in past users of Atrovent(r) CFC MDI ('switchers') and Atrovent(r) naive users. Incidence density rate ratios (with 99% confidence intervals) for events occurring in the first 3 months of exposure (risk period-ID1-3 ) compared to 3 months prior to starting treatment (reference period-IDR ) were calculated. RESULTS: The cohort consisted of 13 211 patients (median age 70 years, 50.1% female; 63.5% prior users of Atrovent(r) CFC MDI ('switchers')). Common respiratory events occurred at higher rates after starting treatment than before for switchers, for example lower respiratory tract infection (LRTI) [ID1 /IDR = 1.45 (99% CI: 1.17, 1.81)] and worsening asthma [ID1 /IDR = 1.58 (99% CI: 1.00, 2.51)]. Of these events only LRTI was significant for Atrovent(r) naive patients [ID1 /IDR = 1.42 (99% CI: 1.04, 1.95)]. CONCLUSIONS: The results of this study suggest effect modification of risk as a result of prior Atrovent(r) CFC MDI use. Overall, Atrovent(r) CFC-free MDI appeared to be reasonably well tolerated in the immediate postmarketing period and the safety profile appeared similar to that of the CFC formulation. PMID- 28990235 TI - Application of 1013 ohm Faraday cup current amplifiers for boron isotopic analyses by solution mode and laser ablation multicollector inductively coupled plasma mass spectrometry. AB - RATIONALE: Boron isotope ratios (delta11 B values) are used as a proxy for seawater paleo-pH, amongst several other applications. The analytical precision can be limited by the detection of low intensity ion beams from limited sample amounts. High-gain amplifiers offer improvements in signal/noise ratio and can be used to increase measurement precision and reduce sample amounts. METHODS: 1013 ohm amplifier technology has previously been applied to several radiogenic systems, but has thus far not been applied to non-traditional stable isotopes. Here we apply 1013 ohm amplifier technology for the measurement of boron isotope ratios using solution mode MC-ICP-MS and laser ablation mode (LA-)MC-ICP-MS techniques. Precision is shown for reference materials as well as for low-volume foraminifera samples. RESULTS: The baseline uncertainty for a 0.1 pA 10 B+ ion beam is reduced to <0.1 0/00 for a typical measurement period. The external precision is better than 0.2 0/00 (2SD) for delta11 B measurements for solution samples containing as little as 0.8 ng total boron. For in situ microanalyses with LA-MC-ICP-MS, the external precision of 11 B/10 B from an in-house calcite standard was 1 0/00 (2SD) for individual spot analyses, and 0.3 0/00 for the mean of >=10 replicate spot analyses. CONCLUSIONS: 1013 ohm amplifier technology is demonstrated to offer advantages for the determination of delta11 B values by both MC-ICP-MS and LA-MC-ICP-MS for small samples of biogenic carbonates, such as foraminifera shells. 1013 ohm amplifier technology will also be of benefit to other non-traditional stable isotope measurements. PMID- 28990236 TI - Spatial organization of silybin biosynthesis in milk thistle [Silybum marianum (L.) Gaertn]. AB - Silymarin is a collection of compounds extracted from the medicinal herb milk thistle, among which silybin is the major flavonolignan. However, the biosynthesis pathway of silybin remains unclear. In this study, biomimetic reactions demonstrated that silybin can be synthesized from coniferyl alcohol and taxifolin by the action of peroxidase. The concentration profiles of silybin and its precursors and RNA-Seq analysis of gene expression revealed that the amount of taxifolin and the activity of peroxidase serve as the limiting factors in silybin biosynthesis. Hierarchical clustering of the expression profile of genes of the flavonoid biosynthesis pathway distinguished flowers from other organs. RNA-Seq revealed five candidates for the peroxidase involved in silybin production, among which APX1 (ascorbate peroxidase 1) showed a distinct peroxidase activity and the capacity to synthesize silybin. The spatial organization of silybin biosynthesis in milk thistle was elucidated, which could help our understanding of the biosynthesis of silybin and other flavonolignans. PMID- 28990238 TI - Early onset canine generalized demodicosis. PMID- 28990237 TI - Dereplication by HPLC-DAD-ESI-MS/MS and Screening for Biological Activities of Byrsonima Species (Malpighiaceae). AB - INTRODUCTION: Byrsonima species have been used in the treatment of gastrointestinal and gynecological inflammations, skin infections and snakebites. Based on their biological activities, it is important to study other organisms from this genus and to identify their metabolites. OBJECTIVES: To determine the metabolic fingerprinting of methanol and ethyl acetate extracts of four Byrsonima species (B. intermedia, B. coccolobifolia, B. verbascifolia and B. sericea) by HPLC-DAD-ESI-MS/MS and evaluate their in vitro antioxidant, anti-glycation, anti inflammatory and cytotoxic activities. MATERIALS AND METHODS: Antioxidant activity was determined by DPPH, ABTS+ and ROO scavenging assays. Anti-glycation activity was evaluated by the ability to inhibit the formation of advanced glycation endproducts (AGEs). Anti-inflammatory activity was evaluated using a murine macrophage cell line (RAW 264-7) in the presence of lipopolysaccharide (LPS). Tumour necrosis factor alpha (TNF-alpha) and nitrite (NO2- ) production were measured by ELISA and the Griess reaction, respectively. The compounds present in the extracts were tentatively identified by HPLC-DAD-ESI-MS/MS. RESULTS: The evaluation of the biological activities showed the potential of the extracts. The activities were assigned to the presence of glycoside flavonoids mainly derived from quercetin, quinic acid derivatives, gallic acid derivatives, galloylquinic acids and proanthocyanidins. Two isomers of sinapic acid-O-hexoside were described for the first time in a Byrsonima species. CONCLUSION: This research contributes to the study of the genus, it is the first report of the chemical composition of B. sericea and demonstrates the importance of the dereplication process, allowing the identification of known compounds without time-consuming procedures. Copyright (c) 2017 John Wiley & Sons, Ltd. PMID- 28990239 TI - Tacrolimus therapy for dermal arteritis of the nasal philtrum refractory to surgery and anti-inflammatory therapy (doxycycline/niacinamide and topical fluocinolone) in a dog. AB - BACKGROUND: Dermal arteritis of the nasal philtrum is a rarely reported condition commonly affecting large breed dogs. OBJECTIVE: To describe the effective treatment of nasal philtrum arteritis with topical tacrolimus in one dog. ANIMAL: A 9-year-old, intact male German shorthair pointer dog was presented with well demarcated deep erythematous ulcers targeting exclusively the skin of the nasal philtrum, accompanied by frequent series of haemorrhage. METHODS: Complete blood count, serum chemistry profile, urinalysis, histopathological examination and immunohistochemistry of skin biopsies. RESULTS: The presence of a V-shaped ulcer with subendothelial spindle cell proliferation resulting in stenosis of dermal arteries and arterioles on histological evaluation, together with a well demarcated deep nasal philtrum ulcer was consistent with arteritis of the nasal philtrum. Treatment was initiated with twice daily oral doxycycline and niacinamide in conjunction with topical fluocinolone cream. Over the course of two years, the lesions progressed with frequent bleeding episodes. A novel surgical approach provided deep resection of all grossly affected tissue; four months later a recurrence of fissures and occasional mild bleeding from the original site was noted and there was no improvement after another two months of oral doxycycline/niacinamide and topical fluocinolone treatment. Topical application of 0.1% tacrolimus twice daily resulted in complete healing of the ulceration and normalization of the epidermis. Over the subsequent 15 months, the dog's lesions remained in remission with topical tacrolimus application twice daily. CONCLUSIONS AND CLINICAL IMPORTANCE: Topical tacrolimus ointment appeared effective at inducing and maintaining lesion remission in this dog with nasal philtrum arteritis. PMID- 28990240 TI - Reduced striato-cortical and inhibitory transcallosal connectivity in the motor circuit of Huntington's disease patients. AB - Huntington's disease (HD) is a neurodegenerative disorder which is primarily associated with striatal degeneration. However, the alterations in connectivity of this structure in HD have been underinvestigated. In this study, we analyzed the functional and structural connectivity of the left putamen, while participants performed a finger-tapping task. Using fMRI and DW-MRI, 30 HD gene expansion carriers (HDGEC) and 29 healthy participants were scanned. Psychophysiological interaction analysis and DTI-based tractography were employed to examine functional and structural connectivity, respectively. Manifest HDGEC exhibited a reduced functional connectivity of the left putamen with the left and the right primary sensorimotor areas (SM1). Based on this result, the inhibitory functional connectivity between the left SM1 and the right SM1 was explored, appearing to be also decreased. In addition, the tract connecting these areas (motor corpus callosum), and the tract connecting the left putamen with the left SM1 appeared disrupted in HDGEC compared to controls. Significant correlations were found between measures of functional and structural connectivity of the motor corpus callosum, showing a coupling of both types of alterations in this tract. The observed reduction of functional and structural connectivity was associated with worse motor scores, which highlights the clinical relevance of these results. Hum Brain Mapp 39:54-71, 2018. (c) 2017 Wiley Periodicals, Inc. PMID- 28990241 TI - Clinically indicated replacement versus routine replacement of peripheral venous catheters in adults: A nonblinded, cluster-randomized trial in China. AB - AIM: The purpose of this study was to investigate the safety of clinically indicated peripheral intravenous catheters (PIVC) replacement intervals. BACKGROUND: Peripheral intravenous catheters are used internationally, including in China where PIVCs are routinely replaced every 72 to 96 hours. Despite some recent international evidence showing such routine replacement is unnecessary, developing countries such as China have no supporting data. METHOD: This cluster randomized trial was conducted between December 2 and December 31, 2013, in 10 internal medicine wards and 10 surgery wards at a tertiary referral teaching hospital in Xiamen, China. Patients were randomly divided into an experimental group (PIVCs were replaced only when clinical indications appeared) and a control group (PIVCs were routinely changed every 72-96 hours). Per-protocol analysis and intention-to-treat analysis were used to analyse the data. Primary end point was the incidence of phlebitis. RESULTS: This study analysed the data of 1198 patients (553 patients in the experimental group and 645 patients in the control group). There were no catheter-related bloodstream infections or local infections in the 2 groups. The 2 groups showed no statistically significant differences in the incidence of phlebitis, catheter occlusion, infiltration, and accidental removal. CONCLUSIONS: Clinically indicated PIVC replacement is feasible, and it may reduce nursing staff workload and patient discomfort. PMID- 28990242 TI - Blood utilization in revision versus first-time cardiac surgery: an update in the era of patient blood management. AB - BACKGROUND: Relative to first-time (primary) cardiac surgery, revision cardiac surgery is associated with increased transfusion requirements, but studies comparing these cohorts were performed before patient blood management (PBM) and blood conservation measures were commonplace. The current study was performed as an update to determine if this finding is still evident in the PBM era. STUDY DESIGN AND METHODS: Primary and revision cardiac surgery cases were compared in a retrospective database analysis at a single tertiary care referral center. Two groups of patients were assessed: 1) those having isolated coronary artery bypass (CAB) or valve surgery and 2) all other cardiac surgeries. Intraoperative and whole hospital transfusion requirements were assessed for the four major blood components. RESULTS: Compared to the primary cardiac surgery patients, the revision surgery patients required approximately twofold more transfused units intraoperatively (p < 0.0001) and approximately two- to threefold more transfused units for the whole hospital stay (p < 0.0001). Intraoperative massive transfusion (>10 red blood cell [RBC] units) was substantially more frequent with revision versus primary cardiac surgery (2.6% vs. 0.1% [p < 0.0001] for isolated CAB or valve and 6.1% vs. 1.9% [p < 0.0001] for all other cardiac surgeries). Revision surgery was an independent risk factor for both moderate (6-10 RBC units) and massive intraoperative transfusion. CONCLUSIONS: In the era of PBM, with restrictive transfusion strategies and a variety of methods for blood conservation, revision cardiac surgery patients continue to have substantially greater transfusion requirements relative to primary cardiac surgery patients. This difference in transfusion requirement was greater than what has been previously reported in the pre-PBM era. PMID- 28990243 TI - MicroRNAs: A novel potential biomarker for diagnosis and therapy in patients with non-small cell lung cancer. AB - BACKGROUND: Lung cancer is still one of the most serious causes of cancer-related deaths all over the world. MicroRNAs (miRNAs) are defined as small non-coding RNAs which could play a pivotal role in post-transcriptional regulation of gene expression. Increasing evidence demonstrated dysregulation of miRNA expression associates with the development and progression of NSCLC. AIMS: To emphasize a variety of tissue-specific miRNAs, circulating miRNAs and miRNA-derived exosomes could be used as potential diagnostic and therapeutic biomarkers in NSCLC patients. MATERIALS & METHODS: In the current review, we paid attention to the significant discoveries of preclinical and clinical studies, which performed on tissue-specific miRNA, circulating miRNA and exosomal miRNA. The related studies were obtained through a systematic search of Pubmed, Web of Science, Embase. RESULTS: A variety of tissue-specific miRNAs and circulating miRNAs with high sensitivity and specificity which could be used as potential diagnostic and therapeutic biomarkers in NSCLC patients. In addition, we emphasize that the miRNA-derived exosomes become novel diagnostic biomarkers potentially in these patients with NSCLC. CONCLUSION: MiRNAs have emerged as non-coding RNAs, which have potential to be candidates for the diagnosis and therapy of NSCLC. PMID- 28990244 TI - A comparison of two tools to screen potentially inappropriate medication in internal medicine patients. AB - WHAT IS KNOWN: Potentially inappropriate medication (PIM) is an important issue for inpatient management; it has been associated with safety problems, such as increases in adverse drugs events, and with longer hospital stays and higher healthcare costs. OBJECTIVE: To compare two PIM-screening tools-STOPP/START and PIM-Check-applied to internal medicine patients. A second objective was to compare the use of PIMs in readmitted and non-readmitted patients. METHOD: A retrospective observational study, in the general internal medicine ward of a Swiss non-university hospital. We analysed a random sample of 50 patients, hospitalized in 2013, whose readmission within 30 days of discharge had been potentially preventable, and compared them to a sample of 50 sex- and age-matched patients who were not readmitted. PIMs were screened using the STOPP/START tool, developed for geriatric patients, and the PIM-Check tool, developed for internal medicine patients. The time needed to perform each patient's analysis was measured. A clinical pharmacist counted and evaluated each PIM detected, based on its clinical relevance to the individual patient's case. The rates of screened and validated PIMs involving readmitted and non-readmitted patients were compared. RESULTS: Across the whole population, PIM-Check and STOPP/START detected 1348 and 537 PIMs, respectively, representing 13.5 and 5.4 PIMs/patient. Screening time was substantially shorter with PIM-Check than with STOPP/START (4 vs 10 minutes, respectively). The clinical pharmacist judged that 45% and 42% of the PIMs detected using PIM-Check and STOPP/START, respectively, were clinically relevant to individual patients' cases. No significant differences in the rates of detected and clinically relevant PIM were found between readmitted and non readmitted patients. WHAT IS NEW AND CONCLUSION: Internal medicine patients are frequently prescribed PIMs. PIM-Check's PIM detection rate was three times higher than STOPP/START's, and its screening time was shorter thanks to its electronic interface. Nearly half of the PIMs detected were judged to be non-clinically relevant, however, potentially overalerting the prescriber. These tools can, nevertheless, be considered useful in daily practice. Furthermore, the relevance of any PIM detected by these tools should always be carefully evaluated within the clinical context surrounding the individual patient. PMID- 28990245 TI - Effects of exposure to six chemical ultraviolet filters commonly used in personal care products on motility of MCF-7 and MDA-MB-231 human breast cancer cells in vitro. AB - Benzophenone (BP)-1, BP-2, BP-3, octylmethoxycinnamate (OMC), 4 methylbenzilidenecamphor and homosalate are added to personal care products to absorb ultraviolet light. Their presence in human milk and their oestrogenic activity suggests a potential to influence breast cancer development. As metastatic tumour spread is the main cause of breast cancer mortality, we have investigated the effects of these compounds on migration and invasion of human breast cancer cell lines. Increased motility of oestrogen-responsive MCF-7 human breast cancer cells was observed after long-term exposure (>20 weeks) to each of the six compounds at >=10-7 m concentrations using three independent assay systems (scratch assay, live cell imaging, xCELLigence technology) and increased invasive activity was observed through matrigel using the xCELLigence system. Increased motility of oestrogen-unresponsive MDA-MB-231 human breast cancer cells was observed after 15 weeks of exposure to each of the six compounds by live cell imaging and xCELLigence technology, implying the increased migratory activity was not confined to oestrogen-responsive cells. Molecular mechanisms varied between compounds and cell lines. Using MCF-7 cells, reduction in E-cadherin was observed following 24 weeks' exposure to 10-5 m BP-1 and 10-5 m homosalate, and reduction in beta-catenin was noted following 24 weeks' exposure to 10-5 m OMC. Using MDA-MB-231 cells, increased levels of matrix metalloproteinase 2 were observed after 15 weeks exposure to 10-7 m OMC and 10-7 m 4 methylbenzilidenecamphor. Although molecular mechanisms differ, these results demonstrate that exposure to any of these six compounds can increase migration and invasion of human breast cancer cells. PMID- 28990246 TI - Excited Delirium: A Systematic Review. AB - OBJECTIVE: We aimed to clarify the definition, epidemiology, and pathophysiology of excited delirium syndrome (ExDS) and to summarize evidence-based treatment recommendations. METHODS: We conducted a systematic literature search of MEDLINE, Ovid, Web of Knowledge, and Cochrane Library for articles published to March 18, 2017. We also searched the gray literature (Google Scholar) and official police or medical expert reports to complete specific epidemiologic data. Search results and full-text articles were independently assessed by two investigators and agreements between reviewers assessed with K statistics. We classified articles by study type, setting, and evidence level. RESULTS: After reviewing the title and abstract of 3,604 references, we fully reviewed 284 potentially relevant references, from which 66 were selected for final review. Six contributed to the definition of ExDS, 24 to its epidemiology, 38 to its pathophysiology, and 27 to its management. The incidence of ExDS varies widely with medical or medicolegal context. Mortality is estimated to be as much as 8.3% to 16.5%. Patients are predominantly male. Male sex, young age, African-American race, and being overweight are independent risk factors. Pathophysiology hypotheses mostly implicate dopaminergic pathways. Most cases occur with psychostimulant use or among psychiatric patients or both. Proposed treatments are symptomatic, often with rapid sedation with benzodiazepines or antipsychotic agents. Ketamine is suggested as an alternative. CONCLUSION: The overall quality of studies was poor. A universally recognized definition is lacking, remaining mostly syndromic and based on clinical subjective criteria. High mortality rate may be due to definition inconsistency and reporting bias. Our results suggest that ExDS is a real clinical entity that still kills people and that has probably specific mechanisms and risk factors. No comparative study has been performed to conclude whether one treatment approach is preferable to another in the case of ExDS. PMID- 28990247 TI - Click and Click-Inspired Chemistry for the Design of Sequence-Controlled Polymers. AB - During the previous decade, many popular chemical reactions used in the area of "click" chemistry and similarly efficient "click-inspired" reactions have been applied for the design of sequence-defined and, more generally, sequence controlled structures. This combination of topics has already made quite a significant impact on scientific research to date and has enabled the synthesis of highly functionalized and complex oligomeric and polymeric structures, which offer the prospect of many exciting further developments and applications in the near future. This minireview highlights the fruitful combination of these two topics for the preparation of sequence-controlled oligomeric and macromolecular structures and showcases the vast number of publications in this field within a relatively short span of time. It is divided into three sections according to the click-(inspired) reaction that has been applied: copper-catalyzed azide-alkyne cycloaddition, thiol-X, and related thiolactone-based reactions, and finally Diels-Alder-chemistry-based routes are outlined, respectively. PMID- 28990248 TI - Exploring the collaboration between formal and informal care from the professional perspective-A thematic synthesis. AB - In Dutch policy and at the societal level, informal caregivers are ideally seen as essential team members when creating, together with professionals, co ordinated support plans for the persons for whom they care. However, collaboration between professionals and informal caregivers is not always effective. This can be explained by the observation that caregivers and professionals have diverse backgrounds and frames of reference regarding providing care. This thematic synthesis sought to examine and understand how professionals experience collaboration with informal caregivers to strengthen the care triad. PubMed, Medline, PsycINFO, Embase, Cochrane/Central and CINAHL were searched systematically until May 2015, using specific key words and inclusion criteria. Twenty-two articles were used for thematic synthesis. Seven themes revealed different reflections by professionals illustrating the complex, multi faceted and dynamic interface of professionals and informal care. Working in collaboration with informal caregivers requires professionals to adopt a different way of functioning. Specific attention should be paid to the informal caregiver, where the focus now is mainly on the client for whom they care. This is difficult to attain due to different restrictions experienced by professionals on policy and individual levels. Specific guidelines and training for the professionals are necessary in the light of the current policy changes in the Netherlands, where an increased emphasis is placed on informal care structures. PMID- 28990249 TI - Berberine inhibits the chemotherapy-induced repopulation by suppressing the arachidonic acid metabolic pathway and phosphorylation of FAK in ovarian cancer. AB - OBJECTIVES: Cytotoxic chemotherapy is an effective and traditional treatment of ovarian cancer. However, chemotherapy-induced apoptosis may also trigger and ultimately accelerate the repopulation of the small number of adjacent surviving cells. This study mainly focused on the tumour cell repopulation caused by chemotherapy in ovarian cancer and the adjunctive/synergistic effect of Berberine on the prevention of tumour repopulation. MATERIALS AND METHODS: The transwell system was used to mimic the co-culture of surviving ovarian cancer cells in the microenvironment of cytotoxic chemotherapy-treated dying cells. Tumour cell proliferation was observed by crystal violet staining. AA and PGE2 levels were measured by ELISA, and changes of protein expression were analysed by Western blot. RESULTS: Chemotherapy drug VP16 treatment triggered AA pathway, leading to the elevated PGE2 level, and ultimately enhanced the repopulation of ovarian cancer cells. Berberine can block the caspase 3-iPLA2 -AA-COX-2-PGE2 pathway by inhibiting the expression of iPLA2 and COX-2. Berberine can also reverse the increased phosphorylation of FAK caused by abnormal PGE2 level and thus reverse the repopulation of ovarian cancer cells after VP16 treatment. CONCLUSIONS: Our observation suggested that Berberine could inhibit the chemotherapy-induced repopulation of ovarian cancer cells by suppressing the AA pathway and phosphorylation of FAK. And these findings implicated a novel combined use of Berberine and chemotherapeutics, which might prevent ovarian cancer recurrence by abrogating early tumour repopulation. PMID- 28990250 TI - Galectin-3 is Persistently Increased in Early Rheumatoid Arthritis (RA) and Associates with Anti-CCP Seropositivity and MRI Bone Lesions, While Early Fibrosis Markers Correlate with Disease Activity. AB - Galectin-3 has been suggested as a pro-inflammatory mediator in animal arthritis and rheumatoid arthritis (RA). We aimed to study the serum level of galectin-3 in patients with newly diagnosed RA and associations with disease profile, Magnetic resonance imaging (MRI) findings and seromarkers of synovial matrix inflammation. One hundred and sixty DMARD naive patients newly diagnosed with RA were included (CIMESTRA study). Clinical, serological and imaging data were recorded before treatment and at 6 weeks, 3 and 12 months. Galectin-3 and hyaluronan (HYA) were measured by ELISA (R&D and Corgenix, USA), and the N-terminal propeptide of type III collagen (PIIINP) by radioimmunoassay (Orion Diagnostica, Finland). One hundred and nineteen, 87 and 60 blood donors served as controls for galectin-3, HYA and PIIINP, respectively. Baseline galectin-3 was significantly elevated in anti-CCP positive (4.2 MUg/l IQR [3.6;6.1]) patients as compared with anti-CCP negatives (4.0 MUg/l [2.6;4.9], P = 0.05) and controls (3.8 MUg/l [3.0;4.8], P < 0.01). During treatment, galectin-3 remained elevated, but increased transiently with peak values at 6 weeks. Galectin-3 correlated with baseline smoking, anti CCP, and with MRI erosion score after 1 year of follow-up. HYA and PIIINP were elevated (P < 0.001) irrespective of anti-CCP status and correlated positively with synovitis assessed clinically and by MRI. HYA and PIIINP did not correlate with galectin-3. These observations indicate that HYA and PIIINP mainly reflect expansive synovitis proliferation while galectin-3 is more closely linked to autoimmunity, smoking and joint destructive processes. PMID- 28990251 TI - Waist-to-calf circumstance ratio is an independent predictor of hepatic steatosis and fibrosis in patients with type 2 diabetes. AB - BACKGROUND AND AIM: Although a combination of central obesity and decreased skeletal muscle mass has been associated with various cardiometabolic disorders, its influence on the presence of non-alcoholic fatty liver disease (NAFLD) in type 2 diabetes (T2D) is unclear. We investigated whether waist-to-calf circumference ratio (WCR) predicts NAFLD or hepatic fibrosis in T2D. METHODS: Patients with T2D (n = 5507) were enrolled in this study. Hepatic steatosis was diagnosed using abdominal ultrasound and predicting score. NAFLD was defined as 'hepatic steatosis absent other causes of chronic liver disease,' such as virus or alcoholism. Degree of hepatic fibrosis was calculated using non-invasive serum biomarker-based models. Insulin resistance was assessed by short insulin tolerance test. RESULTS: The prevalence of NAFLD and obesity (BMI >= 25 kg/m2 , Asian definition) were 46.4% and 38.9%, respectively. NAFLD prevalence was higher with increasing WCR tertiles: lowest tertile (36% in men, 28% in women) versus highest tertile (53.8% in men, 58.2% in women, both P < 0.001 after stratification by insulin resistance status. Increasing WCR tertiles were independently associated with presence of NAFLD: odds ratio (OR) = 1.43, 95% confidence interval (CI) = 1.22-1.68 and OR = 1.56, 95% CI = 1.31-1.86, in the middle and highest tertiles, respectively. Furthermore, patients with NAFLD and the highest WCR tertile had significant fibrosis (OR = 8.62, 95% CI = 1.39-53.36, P = 0.021). Also, WCR was correlated with risk of sarcopenia (OR = 3.18, 95% CI = 2.50-4.05, P < 0.001, highest tertile). CONCLUSIONS: Higher WCR is associated with increased risk of NAFLD and hepatic fibrosis independent of insulin resistance. This suggests that WCR may be a useful index to predict high risk of hepatic steatosis in T2D. PMID- 28990252 TI - Differential brainstem atrophy patterns in multiple sclerosis and neuromyelitis optica spectrum disorders. AB - BACKGROUND: Multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) are central nervous system (CNS) inflammatory demyelinating disorders. It is clinically important to distinguish MS from NMOSD, as treatment and prognosis differ. Brainstem involvement is common in both disorders. PURPOSE: To investigate whether the patterns of brainstem atrophy on volumetric analysis in MS and NMOSD were different and correlated with clinical disability. STUDY TYPE: Case-control cross-sectional study. SUBJECTS: In all, 17 MS, 13 NMOSD, and 18 healthy control (HC) subjects were studied. FIELD STRENGTH/SEQUENCE: T1 -weighted and T2 w spin-echo images were acquired with a 3T scanner. ASSESSMENT: Semiautomated segmentation and volumetric measurement of brainstem regions were performed. Anatomical information was obtained from whole brain T1 w images using a 3D magnetization-prepared rapid gradient-echo (MPRAGE) imaging sequence (TR/TE/T: 7.0/3.2/800 msec, voxel size: 1 * 1 * 1 mm3 , scan time: 10 min 41 sec). STATISTICAL TESTS: Independent samples t-test, Mann-Whitney U-test, partial correlation, and multiple regression analysis. RESULTS: Baseline characteristics were similar across the three groups, without significant difference in disease duration (P = 0.354) and EDSS score (P = 0.159) between MS and NMOSD subjects. Compared to HC, MS subjects had significantly smaller normalized whole brainstem (-5.2%, P = 0.027), midbrain (-8.3%, P = 0.0001), and pons volumes (-5.9%, P = 0.048), while only the normalized medulla volume was significantly smaller in NMOSD subjects compared to HC (-8.5% vs. HC, P = 0.024). Normalized midbrain volume was significantly smaller in MS compared to NMOSD subjects (-5.0%, P = 0.014), whereas normalized medulla volume was significantly smaller in NMOSD compared to MS subjects (-8.1%, P = 0.032). Partial correlations and multiple regression analysis revealed that smaller normalized whole brainstem, pons, and medulla oblongata volumes were associated with greater disability on the Expanded Disability Status Scale (EDSS), Functional System Score (FSS)-brainstem and FSS cerebellar in NMOSD subjects. DATA CONCLUSION: Differential patterns of brainstem atrophy were observed, with the midbrain being most severely affected followed by pons in MS, whereas only the medulla oblongata was affected in NMOSD. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1601 1609. PMID- 28990253 TI - The meaning of empowerment within Italian nursing care settings. AB - AIM: To examine the current state of empowerment of nurses in Italy. BACKGROUND: Empowerment is a broad concept that is also relevant to the field of nursing practice. Its comprehension and use are important because empowerment allows nurses to take control of their own practice. A clear understanding of empowerment is necessary for nurses to take advantage of this important tool. DESIGN: Focus groups were conducted. METHODS: A literature review was performed, and two focus groups were selected between January and February 2014. RESULTS: Sixteen nurses participated in the research. Empowerment is seen as being strongly connected to autonomy and is not associated with power, as the word itself suggests. Italian nurses define empowerment as the creation of conditions that help to establish the possibility for people to develop and express their value and potential. CONCLUSIONS: Empowerment is defined as a condition in which the individual nurse takes control of his/her own practice and thereby provides awareness and confidence to a group. IMPLICATIONS FOR NURSING MANAGEMENT: Italian nurses need to feel appreciated and supported by their own organisations. If warranted, empowerment would allow them to contribute to enhance care, which is the core of the nursing profession. PMID- 28990254 TI - Endoscope-assisted resection of thyroglossal duct cysts via a submaxillary vestibular approach. AB - BACKGROUND: Thyroglossal duct cysts (TDCs) are usually resected through an incision over the entire protruding zone. The resulting scar is aesthetically displeasing, so we explored the use of endoscope-assisted excision of TDCs via a submaxillary vestibular approach. The purpose of this study was to demonstrate the feasibility, validity, and safety of this approach and to evaluate the follow up results. METHODS: From January 2007 to August 2015, 16 patients with TDCs underwent surgical resection using a submaxillary vestibular approach. RESULTS: All procedures were successfully performed using endoscope-assisted surgery via a submaxillary vestibular approach. There were no postoperative complications and no conversions of the operation. The average follow-up period was 73 months (range 14-117 months) without recurrence. All patients and their families were satisfied with the cosmetic results. CONCLUSION: Endoscope-assisted excision of TDCs using a submaxillary vestibular approach is feasible and can be applied effectively and safely with good cosmetic results. Therefore, this method should be considered a viable alternative approach for these patients. PMID- 28990256 TI - Corrigendum. PMID- 28990255 TI - Role of surgery in the treatment of osteoradionecrosis and its complications after radiotherapy for nasopharyngeal carcinoma. AB - BACKGROUND: The purpose of this study was to review the efficacy of surgery for patients with osteoradionecrosis (ORN) after radiotherapy for nasopharyngeal carcinoma (NPC). METHODS: Between 2000 and 2016, we identified 162 patients with skull base ORN, among which 58 patients required surgery. A retrospective medical chart review was performed and the indications and results of surgical interventions were recorded. RESULTS: All surgeries were performed for the treatment of secondary complications of ORN, including central nervous system (CNS) infection (48.4%), blowout bleeding (24.1%), and severe pain (17.2%). Endoscopic debridement was done in 12 patients, whereas the rest required either maxillary swing or mandibulotomy, depending on the location of the necrosis. The majority of the patients required free vastus lateralis flap (72.5%) for reconstruction. Surgery was effective in the control of infection, bleeding, and pain. Multivariate analysis identified reirradiation and bone exposure on MRI as the significant independent risk factors predicting the future need of surgery. CONCLUSION: Surgery is effective in the treatment of secondary complications of skull base ORN after previous radiotherapy for NPC. PMID- 28990257 TI - Validation of the eighth edition American Joint Committee on Cancer staging system for human papillomavirus-associated oropharyngeal cancer. AB - BACKGROUND: The eighth edition American Joint Committee on Cancer (AJCC) staging manual includes major changes in staging of oropharyngeal cancer (OPC). We evaluated the new staging system in order to validate this shift in classification. METHODS: We used the National Cancer Database (NCDB) to identify patients with human papillomavirus-associated (HPV-positive) OPC from 2010-2013. We restaged patients using the eighth edition guidelines and compared them with those from the seventh edition. We calculated stage-specific overall survival and concordance indices. RESULTS: We identified 15 116 patients with a median follow up period of 29.1 months. Clinical and pathological staging changed for 93.9% and 91.7% of patients, respectively. Survival concordance indices for both clinical (0.621-0.656) and pathological (0.640-0.663) staging were improved in the eighth edition compared to the seventh edition. CONCLUSION: The eighth edition guidelines have profoundly altered staging of HPV-positive OPC and seem to demonstrate improved survival discrimination. PMID- 28990259 TI - Isolation and screening of rare Actinobacteria, a new insight for finding natural products with antivascular calcification activity. AB - AIM: Vascular calcification (VC) is a significant pathological process in some life-threatening diseases. Several pathological mechanisms, including transdifferentiation of vascular smooth muscle cells to osteoblast-like cells and apoptosis are involved in VC. Compounds with an inhibitory effect on these processes are potentially efficient medications. In consideration of the multiple biological activities of Actinobacteria, this research was aimed at finding anti VC metabolite-producing Actinobacteria. METHODS AND RESULTS: After the isolation and identification of Actinobacteria, the effect of their fermentation broth extracts on the apoptosis rate was measured using various methods, for example, ethidium bromide/acridine orange staining, DNA laddering and diphenylamine assays. The effect of the most effective fermentation broth extract of Actinobacteria (FBEA) on the mRNA expression of runt-related transcription factor 2 (Runx2) and osteopontin (OPN) was examined. Finally, the most effective FBEA was fractionated and the chemical composition of anti-VC fractions was analysed using GC-MS. Various VC inhibition rates were observed in the tested FBEA (20 MUg ml-1 ; 17.9-60.15%). The inhibition of DNA fragmentation was 7-48%. The FBE with the greatest anticalcification activity belonged to Kribbella sp. UTMC 267 and, according to 16S rRNA analysis, Kribbella sancticallisti with a similarity of 98.53% is its nearest neighbour. The FBE of Kribbella sp. UTMC 267 reduced Runx2 mRNA expression by 2.95-fold and OPN mRNA expression by 28.57-fold, both of which are considered significant (P < 0.05). Finally, GC-MS analysis showed the existence of potent anti-oxidative and anti-inflammation agents in FBE of Kribbella sp. UTMC 267. CONCLUSIONS: Actinobacterial metabolites can provide a new strategy for treating VC diseases by reducing the expression of osteogenic genes, the apoptosis rate and oxidative stress. SIGNIFICANCE AND IMPACT OF THE STUDY: This study highlights the therapeutic potential of Kribbella sp. metabolites and Actinobacteria as a new natural source for drug discovery programs in the nonantibiotic bioactivity field. PMID- 28990260 TI - Combining Charge-Transfer Pathways to Achieve Unique Thermally Activated Delayed Fluorescence Emitters for High-Performance Solution-Processed, Non-doped Blue OLEDs. AB - Two efficient blue thermally activated delayed fluorescence compounds, B-oCz and B-oTC, composed of ortho-donor (D)-acceptor (A) arrangement were designed and synthesized. The significant intramolecular D-A interactions induce a combined charge transfer pathway and thus achieve small DeltaEST and high efficiencies. The concentration quenching can be effectively inhibited in films of these compounds. The blue non-doped organic light emitting diodes (OLEDs) based on B oTC prepared from solution processes shows record-high external quantum efficiency (EQE) of 19.1 %. PMID- 28990258 TI - Baseline connectome modular abnormalities in the childhood phase of a longitudinal study on individuals with chromosome 22q11.2 deletion syndrome. AB - Occurring in at least 1 in 3,000 live births, chromosome 22q11.2 deletion syndrome (22q11DS) produces a complex phenotype that includes a constellation of medical complications such as congenital cardiac defects, immune deficiency, velopharyngeal dysfunction, and characteristic facial dysmorphic features. There is also an increased incidence of psychiatric diagnosis, especially intellectual disability and ADHD in childhood, lifelong anxiety, and a strikingly high rate of schizophrenia spectrum disorders, which occur in around 30% of adults with 22q11DS. Using innovative computational connectomics, we studied how 22q11DS affects high-level network signatures of hierarchical modularity and its intrinsic geometry in 55 children with confirmed 22q11DS and 27 Typically Developing (TD) children. Results identified 3 subgroups within our 22q11DS sample using a K-means clustering approach based on several midline structural measures-of-interests. Each subgroup exhibited distinct patterns of connectome abnormalities. Subtype 1, containing individuals with generally healthy-looking brains, exhibited no significant differences in either modularity or intrinsic geometry when compared with TD. By contrast, the more anomalous 22q11DS Subtypes 2 and 3 brains revealed significant modular differences in the right hemisphere, while Subtype 3 (the most anomalous anatomy) further exhibited significantly abnormal connectome intrinsic geometry in the form of left-right temporal disintegration. Taken together, our findings supported an overall picture of (a) anterior-posteriorly differential interlobar frontotemporal/frontoparietal dysconnectivity in Subtypes 2 and 3 and (b) differential intralobar dysconnectivity in Subtype 3. Our ongoing studies are focusing on whether these subtypes and their connnectome signatures might be valid biomarkers for predicting the degree of psychosis-proneness risk found in 22q11DS. Hum Brain Mapp 39:232-248, 2018. (c) 2017 Wiley Periodicals, Inc. PMID- 28990262 TI - Effect of feed intake level and dietary protein content on the body temperature of pigs housed under thermo neutral conditions. AB - Feed intake and diet composition appear to affect the body temperature of pigs. Two trials were conducted to analyse the effect of feed intake level and dietary protein content on the intestinal temperature (IT) of pigs housed under thermo neutral conditions. Ten pigs (64.1 +/- 1.3 kg initial body weight) fitted with an ileal cannula were used. A thermometer set to register the IT at 5-min intervals was implanted into the ileum through the cannula. In both trials, the ambient temperature ranged from 19.1 to 21.6 degrees C and the pigs were fed at 07:00 and 19:00 hr (same amount each time). In trial 1, the pigs were fed daily 1.2 or 1.8 kg of a wheat-soybean meal diet. The IT followed a similar pattern along a 24-hr period regardless the feed intake level. The IT rapidly increased up to 0.61 and 0.74 degrees C after the morning meal and up to 0.53 and 0.47 degrees C after the evening meal in pigs fed 1.2 and 1.8 kg/d respectively. The postprandial IT was higher in pigs fed 1.8 kg after each meal (p < .05). In trial 2, pigs were fed daily 1.8 kg of a low (11%) or a high (22%) crude protein diet. The IT followed a similar pattern along the 24-hr period regardless the dietary protein level. The postprandial IT did not differ between pigs fed the low protein or the high protein (p > .10). The IT rapidly increased up to 0.66 and 0.62 degrees C after the morning meal in pigs fed the high- and low-protein diet (p < .05), but there was no change after the evening meal (p > .10). In conclusion, the feed intake level affected the IT of pigs housed under TN conditions, but the dietary protein content had no effect. PMID- 28990261 TI - Heated air humidification versus cold air nebulization in newly tracheostomized patients. AB - BACKGROUND: After tracheostomy, the airway lacks an essential mechanism for warming and humidifying the inspired air with the consequent functional impairment and discomfort. The purpose of this study was to compare airway hydration with cold-air nebulization versus heated high-flow humidification on medical interventions and tracheal ciliary beat frequency (CBF). METHODS: Newly tracheostomized patients (n = 20) were treated either with cold-air nebulization or heated humidification. The number of required tracheal suctioning procedures to clean the trachea and tracheal CBF were assessed. RESULTS: The number of required suctions per day was significantly lower in the heated humidification group with medians 3 versus 5 times per day. Mean CBF was significantly higher in the heated humidification group (6.36 +/- 1.49 Hz) compared to the cold-air nebulization group (3.99 +/- 1.39 Hz). CONCLUSION: The data suggest that heated humidification enhanced mucociliary transport leading to a reduced number of required suctioning procedures in the trachea, which may improve postoperative patient care. PMID- 28990263 TI - Early aspirin initiation following heart transplantation is associated with reduced risk of allograft vasculopathy during long-term follow-up. AB - AIM: Cardiac allograft vasculopathy (CAV) is a major cause of morbidity and mortality after heart transplantation (HT). Enhanced platelet reactivity is a contributing factor. We aimed to investigate the association between early initiation of aspirin therapy post-HT and the 15-year risk of the development of CAV. METHODS: We studied 206 patients who underwent HT between 1991 and 2016. Multivariate Cox proportional hazards regression modeling was employed to evaluate the association between early aspirin initiation and the long-term risk of CAV. RESULTS: Ninety-seven patients (47%) received aspirin therapy. At 15 years of follow-up, the rate of CAV was lowered by sixfold in patients treated with aspirin compared with the non-treated patients: 7% vs 37% (log-rank P value<.001). The corresponding rates of the combined end-point of CAV or death were also lower in patients treated with aspirin, compared with the non-treated patients: 42% vs 78% (log-rank P < .001). Consistently, multivariate analysis showed that early aspirin therapy was associated with a significant 84% (P < .001) reduction in CAV risk, and with a corresponding 68% (P < .0001) reduction in the risk of the combined end-point of CAV or death. We further validated these results using a propensity score-adjusted Cox model. CONCLUSIONS: Early aspirin initiation is independently associated with a significant reduction in the risk of CAV. PMID- 28990265 TI - Physical activity interventions are delivered consistently across hospitalized older adults but multimorbidity is associated with poorer rehabilitation outcomes: A population-based cohort study. AB - BACKGROUND: Older adults live with multimorbidity including frailty and cognitive impairment often requiring hospitalization. While physical activity interventions (PAIs) are a normal rehabilitative treatment, their clinical effect in hospitalized older adults is uncertain. OBJECTIVE: To observe PAI dosing characteristics and determine their impact on clinical performance parameters. DESIGN: A single-site prospective observational cohort study in an older persons' unit. SUBJECTS: Seventy-five older persons' unit patients >=65 years. INTERVENTION: PAI; therapeutic contact between physiotherapy clinician and patient. MEASUREMENTS: Parameters included changes in activities-of-daily-living (Barthel Index), handgrip strength, balance confidence, and gait velocity, measured between admission and discharge (episode). Dosing characteristics were PAI temporal initiation, frequency, and duration. Frailty/cognition status was dichotomized independently per participant yielding 4 subgroups: frail/nonfrail and cognitively-impaired/cognitively-unimpaired. RESULTS: Median (interquartile range) PAI initiation occurred after 2 days (1-4), frequency was 0.4 PAIs per day (0.3-0.5), and PAI duration per episode was 3.75 hours (1.8-7.2). All clinical parameters improved significantly across episodes: grip strength median (interquartile range) change, 2.0 kg (0.0-2.3) (P < .01); Barthel Index, 5 (3-8) (P < .01); gait velocity, 0.06 m.?s-1 (0.06-0.16) (P < .01); and balance confidence, -3 (-6 to -1) (P < .01). Physical activity intervention dosing remained consistent within subgroups. While several moderate to large associations between amount of PAIs and change in clinical parameters were observed, most were within unimpaired subgroups. CONCLUSIONS: PAI dosing is consistent. However, while clinical changes during hospital episodes are positive, more favourable responses to PAIs occur if patients are nonfrail/cognitively-unimpaired. Therefore, to deliver a personalized rehabilitation approach, adaptation of PAI dose based on patient presentation is desirable. PMID- 28990264 TI - Consistency of magnetoencephalographic functional connectivity and network reconstruction using a template versus native MRI for co-registration. AB - INTRODUCTION: Studies using functional connectivity and network analyses based on magnetoencephalography (MEG) with source localization are rapidly emerging in neuroscientific literature. However, these analyses currently depend on the availability of costly and sometimes burdensome individual MR scans for co registration. We evaluated the consistency of these measures when using a template MRI, instead of native MRI, for the analysis of functional connectivity and network topology. METHODS: Seventeen healthy participants underwent resting state eyes-closed MEG and anatomical MRI. These data were projected into source space using an atlas-based peak voxel and a centroid beamforming approach either using (1) participants' native MRIs or (2) the Montreal Neurological Institute's template. For both methods, time series were reconstructed from 78 cortical atlas regions. Relative power was determined in six classical frequency bands per region and globally averaged. Functional connectivity (phase lag index) between each pair of regions was calculated. The adjacency matrices were then used to reconstruct functional networks, of which regional and global metrics were determined. Intraclass correlation coefficients were calculated and Bland-Altman plots were made to quantify the consistency and potential bias of the use of template versus native MRI. RESULTS: Co-registration with the template yielded largely consistent relative power, connectivity, and network estimates compared to native MRI. DISCUSSION: These findings indicate that there is no (systematic) bias or inconsistency between template and native MRI co-registration of MEG. They open up possibilities for retrospective and prospective analyses to MEG datasets in the general population that have no native MRIs available. Hum Brain Mapp, 2017. (c) 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. Hum Brain Mapp 39:104-119, 2018. (c) 2017 Wiley Periodicals, Inc. PMID- 28990266 TI - Nickel-Catalyzed Cyanation of Aryl Chlorides and Triflates Using Butyronitrile: Merging Retro-hydrocyanation with Cross-Coupling. AB - We describe a nickel-catalyzed cyanation reaction of aryl (pseudo)halides that employs butyronitrile as a cyanating reagent instead of highly toxic cyanide salts. A dual catalytic cycle merging retro-hydrocyanation and cross-coupling enables the conversion of a broad array of aryl chlorides and aryl/vinyl triflates into their corresponding nitriles. This new reaction provides a strategically distinct approach to the safe preparation of aryl cyanides, which are essential compounds in agrochemistry and medicinal chemistry. PMID- 28990267 TI - The role of identity in committing acts of violent extremism - and in desisting from them. PMID- 28990268 TI - Extended suicide. PMID- 28990269 TI - Sexual behaviour in preschool children in the context of intraparental violence and sexual coercion. PMID- 28990270 TI - Impact of low alcohol verbal descriptors on perceived strength: An experimental study. AB - OBJECTIVES: Low alcohol labels are a set of labels that carry descriptors such as 'low' or 'lighter' to denote alcohol content in beverages. There is growing interest from policymakers and producers in lower strength alcohol products. However, there is a lack of evidence on how the general population perceives verbal descriptors of strength. The present research examines consumers' perceptions of strength (% ABV) and appeal of alcohol products using low or high alcohol verbal descriptors. DESIGN: A within-subjects experimental study in which participants rated the strength and appeal of 18 terms denoting low (nine terms), high (eight terms) and regular (one term) strengths for either (1) wine or (2) beer according to drinking preference. METHODS: Thousand six hundred adults (796 wine and 804 beer drinkers) sampled from a nationally representative UK panel. RESULTS: Low, Lower, Light, Lighter, and Reduced formed a cluster and were rated as denoting lower strength products than Regular, but higher strength than the cluster with intensifiers consisting of Extra Low, Super Low, Extra Light, and Super Light. Similar clustering in perceived strength was observed amongst the high verbal descriptors. Regular was the most appealing strength descriptor, with the low and high verbal descriptors using intensifiers rated least appealing. CONCLUSIONS: The perceived strength and appeal of alcohol products diminished the more the verbal descriptors implied a deviation from Regular. The implications of these findings are discussed in terms of policy implications for lower strength alcohol labelling and associated public health outcomes. Statement of contribution What is already known about this subject? Current UK and EU legislation limits the number of low strength verbal descriptors and the associated alcohol by volume (ABV) to 1.2% ABV and lower. There is growing interest from policymakers and producers to extend the range of lower strength alcohol products above the current cap of 1.2% ABV set out in national legislation. There is a lack of evidence on how the general population perceives verbal descriptors of alcohol product strength (both low and high). What does this study add? Verbal descriptors of lower strength wine and beer form two clusters and effectively communicate reduced alcohol content. Low, Lower, Light, Lighter, and Reduced were considered lower in strength than Regular (average % ABV). Descriptors using intensifiers (Extra Low, Super Low, Extra Light, and Super Light) were considered lowest in strength. Similar clustering in perceived strength was observed amongst the high verbal descriptors. The appeal of alcohol products reduced the more the verbal descriptors implied a deviation from Regular. PMID- 28990271 TI - In Situ GIWAXS Analysis of Solvent and Additive Effects on PTB7 Thin Film Microstructure Evolution during Spin Coating. AB - The influence of solvent and processing additives on the pathways and rates of crystalline morphology formation for spin-coated semiconducting PTB7 (poly[[4,8 bis[(2-ethylhexyl)oxy]benzo[1,2-b:4,5-b']dithiophene-2,6-diyl][3-fluoro-2-[(2 ethylhexyl)-carbonyl]-thieno[3,4-b]thiophenediyl]]) thin films is investigated by in situ grazing incidence wide-angle X-ray scattering (GIWAXS) and optical reflectance, to better understand polymer solar cell (PSC) optimization approaches. In situ characterization of PTB7 film formation from chloroform (CF), chlorobenzene (CB), and 1,2-dichlorobenzene (DCB) solutions, as well as CB solutions with 1% and 3% v/v of the processing additives 1-chloronapthalene (CN), diphenylether (DPE), and 1,8-diiodooctane (DIO), reveals multiple crystallization pathways with: (i) single-solvent systems exhibiting rapid (<3 s) crystallization after a solvent boiling point-dependent film thinning transition, (ii) solvent + additive systems exhibiting different crystallization pathways and crystallite formation times from minutes (CN, DPE) to 1.5 h (DIO). Identifying crystalline intermediates has implications for bulk-heterojunction PSC morphology optimization via optimized spin-casting processes. PMID- 28990272 TI - Impact of bladder cancer on health-related quality of life. AB - OBJECTIVES: To identify changes in health-related quality of life (HRQoL) after diagnosis of bladder cancer in older adults in comparison with a group of adults without bladder cancer (controls). PATIENTS AND METHODS: Data from the Surveillance, Epidemiology and End Results registries were linked with Medicare Health Outcomes Survey (MHOS) data. Medicare beneficiaries aged >=65 years in the period 1998-2013, who were diagnosed with bladder cancer between baseline and follow-up through the MHOS, were matched with control subjects without cancer using propensity scores. Linear mixed models were used to estimate predictors of HRQoL changes. RESULTS: After matching, 535 patients with bladder cancer (458 non muscle-invasive bladder cancer [NMIBC] and 77 with muscle-invasive bladder cancer [MIBC]) and 2 770 control subjects without cancer were identified. Both patients with NMIBC and those with MIBC reported significant declines in HRQoL scores over time vs controls: physical component summary -2 and -5.3 vs -0.4, respectively; bodily pain -1.9 and -3.6 vs -0.7; role physical -2.7 and -4.7 vs -0.7; general health -2.4 and -6.1 vs 0; vitality -1.2 and -3.5 vs -0.1; and social functioning -2.1 and -5.7 vs -0.8. All scores ranged from 0 to 100. When stratified by time since diagnosis, HRQoL improved over 1 year for some domains (role physical), but remained lower across most domains. CONCLUSIONS: After diagnosis, patients with bladder cancer experienced significant declines in physical, mental and social HRQoL relative to controls. Decrements were most pronounced among individuals with MIBC. Methods to better understand and address HRQoL decrements among patients with bladder cancer are needed. PMID- 28990273 TI - Exercise ventilatory inefficiency in heart failure: some fresh news into the roadmap of heart failure with preserved ejection fraction phenotyping. PMID- 28990274 TI - Optimizing Multiplexed Detections of Diabetes Antibodies via Quantitative Microfluidic Droplet Array. AB - Sensitive, single volume detections of multiple diabetes antibodies can provide immunoprofiling and early screening of at-risk patients. To advance the state-of the-art suspension assays for diabetes antibodies, porous hydrogel droplets are leveraged in microfluidic serpentine arrays to enhance reagent transport. This spatially multiplexed assay is applied to the detection of antibodies against insulin, glutamic acid decarboxylase, and insulinoma-associated protein 2. Optimization of assay protocol results in a shortened assay time of 2 h, with better than 20 pg mL Supporting Information detection limits across all three antibodies. Specificity and cross-reactivity tests show negligible background, nonspecific antibody-antigen, and nonspecific antibody-antibody bindings. Multiplexed detections are able to measure within 15% of target concentrations from low to high ranges. The technique enables quantifications of as little as 8000 molecules in each 500 um droplet in a single volume, multiplexed assay format, a breakthrough necessary for the adoption of diabetes panels for clinical screening and monitoring in the future. PMID- 28990275 TI - Iron status measurement in routine heart failure assessment: a call for action. PMID- 28990277 TI - The efficacy of using exogenous enzymes cocktail on production, egg quality, egg nutrients and blood metabolites of laying hens fed distiller's dried grains with solubles. AB - An experiment was performed using 120 Hisex Brown laying hens for evaluating the effects of different inclusion levels of corn distiller's dried grains with solubles (DDGS) as a replacement of soybean meal (SBM) with or without enzyme cocktail on performance, egg quality, egg nutrients and blood metabolites in laying hens through 22-42 weeks of age. A 4 * 2 factorial design experiment was performed including four substitution levels of DDGS (0, 250, 500 and 750 g/kg respectively) and two enzyme cocktail levels (0 and 250 mg/kg diet). The used enzyme in this study "Gallazyme" composed of xylanase, Trichoderma longibrachiatum (600 units/g), protease, Bacillus subtilis (8,000 units/g) and amylase and Bacillus amyloliquofaciens (800 units/g). The control diet showed the best feed efficiency followed by the intermediate levels of DDGS. The lowest value of feed efficiency was found in the group fed the highest level of DDGS. Enzyme addition improved feed efficiency and decreased laying rate. Increasing DDGS levels was associated with albumin and shell thickness increases. Dietary DDGS depressed all egg components except the organic matter which maximised in enzyme-treated groups. Increasing DDGS level was accompanied by increase in yolk cholesterol and total lipids. No significant impacts were detected with enzymes supplementation on yolk lipids profile. Excepting serum calcium and phosphorous, all serum constituents increased with increasing level of DDGS. Using enzyme markedly depressed serum ammonia by 15.02% and increased calcium by 6.44% compared with enzyme-free diets. Interaction between DDGS and enzyme was significant on most of studied parameters. It could be concluded that using enzyme cocktail in DDGS-based diets may improve feed efficiency and egg quality, in addition to lowering blood ammonia and increasing blood calcium. It is recommended to substitute SBM by DDGS up to 500 g/kg diet. PMID- 28990278 TI - Generalized Self-Doping Engineering towards Ultrathin and Large-Sized Two Dimensional Homologous Perovskites. AB - Two-dimensional (2D) homologous perovskites are arousing intense interest in photovoltaics and light-emitting fields, attributing to significantly improved stability and increasing optoelectronic performance. However, investigations on 2D homologous perovskites with ultrathin thickness and large lateral dimension have been seldom reported, being mainly hindered by challenges in synthesis. A generalized self-doping directed synthesis of ultrathin 2D homologous (BA)2 (MA)n 1 Pbn Br3n+1 (17-fold extension in relaxation time and almost 10-fold improvement in polarization level when compared to its unoptimized structure. PMID- 28990280 TI - Soil microbiota respond to green manure in organic vineyards. AB - AIMS: The aim of this work was to investigate the effects of biodynamic management with and without the addition of green manure, in comparison with organic management, on the microbiota in vineyards soil. METHODS AND RESULTS: High throughput sequencing was used to compare the taxonomic structure of the soil bacterial and fungal communities from vineyards managed with different methods (organic, biodynamic or biodynamic with green manure). Our results showed that microbial communities associated with biodynamic and organic farming systems were very similar, while green manure was the greatest source of soil microbial biodiversity and significantly changed microbial richness and community composition compared with other soils. Green manure also significantly enriched bacterial taxa involved in the soil nitrogen cycle (e.g. Microvirga sp., Pontibacter sp. and Nitrospira sp.). CONCLUSIONS: Our results showed that the diversity and composition of the microbial communities associated with biodynamic and organic farming systems were similar, indicating that the use of biodynamic preparations 500 and 501 did not cause any significant detectable changes to the soil microbial community in the short term, while the effects of green manure were significant in soil microbiota. SIGNIFICANCE AND IMPACT OF THE STUDY: The microbiological richness and structure of soil are used as a sensitive indicator of soil quality. The extension of organic/biodynamic farming, associated with green manure application, could contribute to increase the abundance of functional groups of biological and agronomical relevance and maintaining microbial biodiversity in vineyard soils. PMID- 28990281 TI - Mass spectrometry in untargeted liquid chromatography/mass spectrometry metabolomics: Electrospray ionisation parameters and global coverage of the metabolome. AB - RATIONALE: Liquid chromatography coupled to mass spectrometry (LC/MS) is a dominant analytical platform in metabolomics, because of the high sensitivity and resolution, thus enabling large-scale coverage of metabolomes. Correspondingly, electrospray ionisation (ESI) is the favoured ionisation method in untargeted LC/MS metabolomics given the ability to produce large numbers of ions. In the workflow of LC/ESI-MS metabolomics, maximising the ionisation efficiency over a wide mass range is inevitably an essential and determining step, subsequently defining the extent of coverage of the metabolome under investigation. Thus in this study, electronic factors related to the functioning of the ESI source, namely the capillary and sample cone voltages, were explored to investigate the influence on the data acquired in metabolomic investigations. METHODS: Hydromethanolic samples from an untargeted study (sorghum plants responding dynamically to fungal infection) were analysed on a high-resolution/definition LC/ESI-MS system. Here the capillary and sample cone voltages of the ZSprayTM ESI source were varied between 1.5-3.0 kV and 10.0-40.0 V, respectively. The acquired data were processed with MarkerLynxTM software and analysed using central composite design response surface methodology and chemometric approaches (principal component analysis and orthogonal projection latent structures discriminant analysis). RESULTS: The results evidently demonstrate that both capillary and sampling cone voltages not only significantly influence the recorded MS signals with regard to the number and abundance of features, but also the overall structure of the collected data. This consequently impacts on the information extracted from the data and thus affects coverage of the metabolome. CONCLUSIONS: The observations postulate in that, untargeted LC/MS metabolomics, 'what you see is what you ionise'. Although there is convergence of collected data under different ESI conditions, the nuances observed indicate that the exploration of different ion source settings could be the best trade-off in expanding and maximising the metabolome coverage in untargeted metabolomic experiments. PMID- 28990282 TI - Use of oral mucosal cell sheets for accelerated oral surgical wound healing. AB - BACKGROUND: We developed a highly efficient in vitro-engineered mucosa equivalent using completely autologous mucosa and blood and investigated its feasibility and efficacy for oral surgical wound healing. METHODS: Small oral mucosa samples were obtained from surgical patients, and keratinocytes and fibroblasts were primarily grown in media without animal products for generating 3D cell sheets. RESULTS: Morphological characteristics of the cell sheets were comparable to those of human mucosa, although p63-positive cells were more numerous in cell sheets. In addition, cell sheets were flexible, expandable, and easy to handle or transfer. In further in vivo rat experiments with deep wounding of the buccal mucosa and soft tissues, controls had significantly thinner epithelium and thicker collagen densities than those with cell sheets. CONCLUSION: Autologous cell sheets can be engineered in vitro from oral keratinocytes, fibroblasts, and fibrin, and can be used clinically to accelerate healing of oral soft tissue defects. PMID- 28990283 TI - Metastatic spread from squamous cell carcinoma of the hypopharynx to the totally implantable venous access port insertion site: Case report and review of literature. AB - BACKGROUND: The totally implantable venous access port plays a crucial role in delivering chemotherapy in the outpatient setting. Here, we report the first case of a patient with hypopharyngeal tumor who developed chest wall metastasis over the totally implantable venous access port inserted in the internal jugular vein. METHODS: Our patient, a 58-year-old man with a hypopharyngeal tumor presented with a lump over the totally implantable venous access port site. The port was removed and the lump was biopsied. The CT studies showed that the tumor had spread along the catheter from the hypopharynx to the chest wall. RESULTS: The pathology from the biopsy showed squamous cell carcinoma (SCC). The patient had poor performance status and opted for hospice care. CONCLUSION: We present a novel case of metastasis over the totally implantable venous access port implanted in a patient with a hypopharyngeal tumor. We also reviewed relevant literature comparing the data from percutaneous endoscopic gastrostomy (PEG) tube site metastasis with our patient and other similar case reports. PMID- 28990285 TI - Green and Efficient Processing of Cinnamomum cassia Bark by Using Ionic Liquids: Extraction of Essential Oil and Construction of UV-Resistant Composite Films from Residual Biomass. AB - There is significant interest in the development of a sustainable and integrated process for the extraction of essential oils and separation of biopolymers by using novel and efficient solvent systems. Herein, cassia essential oil enriched in coumarin is extracted from Cinnamomum cassia bark by using a protic ionic liquid (IL), ethylammonium nitrate (EAN), through dissolution and the creation of a biphasic system with the help of diethyl ether. The process has been perfected, in terms of higher biomass dissolution ability and essential oil yield through the addition of aprotic ILs (based on the 1-butyl-3-methylimidazolium (C4 mim) cation and chloride or acetate anions) to EAN. After extraction of oil, cellulose rich material and free lignin were regenerated from biomass-IL solutions by using a 1:1 mixture of acetone-water. The purity of the extracted essential oil and biopolymers were ascertained by means of FTIR spectroscopy, NMR spectroscopy, and GC-MS techniques. Because lignin contains UV-blocking chromophores, the oil-free residual lignocellulosic material has been directly utilized to construct UV light-resistant composite materials in conjunction with the biopolymer chitosan. Composite material thus obtained was processed to form biodegradable films, which were characterized for mechanical and optical properties. The films showed excellent UV-light resistance and mechanical properties, thereby making it a material suitable for packaging and light-sensitive applications. PMID- 28990286 TI - A new practical classification for spatial distribution and morphology of human hair: Ahmad's LGMA classification. AB - BACKGROUND: The human hair is a complex structure with a diversity within itself. There is a wide variation in distribution and spatial arrangement of hairs. METHODS: The current classification was developed on the basis of high-resolution photographs of adult human scalp. RESULTS: On the observation, the new classification consisted of 4 categories. CONCLUSIONS: It will help the hair restoration surgeons and dermatologists to identify the various pattern and also to help in deciding the appropriate size of the punch in FUE. PMID- 28990284 TI - The oncogenic role of Epstein-Barr virus-encoded microRNAs in Epstein-Barr virus associated gastric carcinoma. AB - Epstein-Barr virus (EBV) infection is detected in various epithelial malignancies, such as nasopharyngeal carcinoma (NPC) and gastric cancer (GC). EBV comprises some unique molecular features and encodes viral genes and microRNAs (miRNAs) by its own DNA sequence. EBV genes are required to maintain latency and contribute to oncogenic property. miRNAs encoded by EBV have been shown to contribute to initiation and progression of EBV-related malignancies. By a number of genomic profiling studies, some EBV miRNAs were confirmed to be highly expressed in EBV-associated gastric cancer (EBVaGC) samples and cell lines. The majority host targets of the EBV miRNAs are important for promoting cell growth and inhibiting apoptosis, facilitating cell survival and immune evasion. However, the integrated molecular mechanisms related to EBV miRNAs remain to be investigated. In this review, we summarized the crucial role of EBV miRNAs in epithelial malignancies, especially in EBVaGC. Collectively, EBV miRNAs play a significant role in the viral and host gene regulation network. Understanding the comprehensive potential targets and relevant functions of EBV miRNAs in gastric carcinogenesis might provide better clinical translation. PMID- 28990287 TI - Mesenchymal-like stem cells in canine ovary show high differentiation potential. AB - OBJECTIVES: Recent studies have reported the existence of stem cells in ovarian tissue that show enhanced proliferative and differentiation potential compared to other adult tissues. Based on this evidence, we hypothesized that ovarian tissue contained mesenchymal-like stem cells (MSC) that could be isolated using a novel rapid plastic adhesion technique. MATERIALS AND METHODS: We established MSC lines derived from ovarian and adipose tissue based on their ability to rapidly adhere to plastic culture dishes in the first 3 hours after plating and studied their potentiality in terms of molecular markers and differentiation capacity. RESULTS: Morphological and kinetic properties of in vitro cultured ovarian MSC were similar to adipose-derived MSC, and both reached senescence after similar passage numbers. Ovarian-derived MSC expressed mesenchymal (CD90 and CD44) but not haematopoietic markers (CD34 and CD45), indicating similarity to adipose-derived MSC. Moreover, ovarian-derived MSC expressed NANOG, TERT, SOX2, OCT4 and showed extensive capacity to differentiate not only into adipogenic, osteogenic and chondrogenic tissue but also towards neurogenic and endodermal lineages and even precursors of primordial germ cells. CONCLUSION: These results show for the first time the derivation of ovarian cells with the molecular properties of MSC as well as wide differentiation potential. Canine ovarian tissue is accessible, expandable, multipotent and has high plasticity, holding promise for applications in regenerative medicine. PMID- 28990288 TI - Comparing the broad socio-cognitive profile of youth with Williams syndrome and 22q11.2 deletion syndrome. AB - BACKGROUND: Numerous studies have assessed the socio-cognitive profile in Williams syndrome (WS) and, independently, in 22q11.2 deletion syndrome (22q11.2DS). Yet, a cross-syndrome comparison of these abilities between individuals with these two syndromes with known social deficits has not been conducted. METHODS: Eighty-two children participated in four study groups: WS (n = 18), 22q112.DS (n = 24), age-matched individuals with idiopathic developmental disability (IDD; n = 20) and typically developing (TD) controls (n = 20). Participants completed four socio-cognitive tests: facial emotion recognition, mental state attribution, differentiating real from apparent emotions and trait inference based on motives and actions-outcomes. RESULTS: The current findings demonstrate that children with WS were better in labelling happy faces compared with children with 22q11.2DS, partially reflecting their exaggerated social drive. In the false belief task, however, the WS and IDD groups performed poorly compared with the 22q11.2DS group, possibly due to their difficulty to interpret subtle social cues. When asked to identify the gap between real-negative vs. apparent-positive emotions, the 22q11.2DS group performed similarly to TD children but better than the WS group, possibly due to their anxious personality and their innate bias towards negatively valence cues. Finally, individuals with WS were more willing to become friends with a story character even when the character's motives were negative, reflecting their difficulty to avoid potentially harmful real-life situations. CONCLUSIONS: Overall, our multi-facet socio-cognitive battery uncovered strengths and weaknesses in social cognition that are syndrome-specific, shared among the genetic syndromes, or common to the three clinical groups compared with healthy controls. Our findings underscore the need to devise age-specific and condition-specific assessment tools and intervention programs towards improving these children's socio-cognitive deficits. PMID- 28990289 TI - Valproate Plays a Protective Role against Migraine by Inhibiting Protein Kinase C Signalling in Nitroglycerin-treated Mice. AB - Migraine is a common disease with a high morbidity. Valproate (VP) is used as an anti-epilepsy drug in clinic. This study aimed to investigate the role of VP in nitroglycerin (NTG)-induced migraine using a mouse model. NTG was employed by intraperitoneal injection to induce a migraine model in mice. The NTG administration caused mouse head discomforts, decreased tolerance to cold or hot stimulation and increased content of nitric oxide, calcitonin gene-related peptide and neuropeptide Y in serum, which were ameliorated by intraperitoneal injection of VP. The levels of two inflammatory factors, interleukin (IL)-1beta and inducible nitric oxide synthase, in dura mater were increased by NTG treatment, while the increase was attenuated by application of VP. In addition, the phosphorylation levels of protein kinase C (PKC) alpha, gamma, delta and epsilon were increased by NTG and decreased by VP. However, their total expression at the transcriptional and translational levels did not change significantly. Two substrates of PKC, cAMP-response element binding protein 1 and signal transducer and activator of transcription 1 were also phosphorylated by NTG application, and the phosphorylation level was attenuated by VP, consistent with the change of PKC informs. Together, we demonstrated that VP prevented damage due to migraine by inhibiting PKC signalling in NTG-injected mice, which may provide a basis for investigating the clinical treatment of migraine. PMID- 28990290 TI - Synthesis, Characterization, Antimicrobial Activity, and Docking Studies of New Triazolic Tripodal Ligands. AB - The synthesis and characterization of new N-donor bitriazolic tripods were reported. The in vitro antibacterial and antifungal activities of these products were screened against fungal strain (Candida pelliculosa) and against four bacterial strains (Micrococcus luteus, Bacillus subtilis, Listeria innocua, and Escherichia coli). Biological data revealed the effect of the chemical structure on antimicrobial activity. Molecular docking studies of some compounds showed that they could act as inhibitors for the biotin carboxylase enzyme. PMID- 28990292 TI - Investigating the impact of the universal healthcare coverage programme on community pharmacy practice. AB - The introduction of Universal Healthcare Coverage (JKN) in 2014 has changed the landscape of the Indonesian healthcare and affected the community pharmacy sector. This paper investigates perceptions of healthcare and pharmacy stakeholders about the impact of JKN on the practice of pharmacists and pharmacy in both public (Puskesmas) and private (Community or Retail pharmacy) settings. In-depth, semi-structured interviews were conducted from February to August 2016 involving 29 participants representing key stakeholders from different provinces in Indonesia. While JKN was actually designed with good policy objectives for pharmacy integration within primary care network, it has created some unintended and unanticipated distortion in the healthcare system which may be detrimental to the community pharmacy sector. In fact, community pharmacy practice is still limited to dispensing and continued to be hampered by ongoing challenges mainly pharmacists' absence, lack of clinical competence and limited support from regulation changes. It is a missed opportunity for pharmacists to play a greater role in primary care services indicating the need for an overhaul to pharmacy education and policy system. PMID- 28990291 TI - Performance evaluation of the automated nucleated red blood cell count of five commercial hematological analyzers. AB - INTRODUCTION: Recent automated hematology analyzers (HAs) can identify and report nucleated red blood cells (NRBC) count as a separate population out of white blood cells (WBC). The aim of this study was to investigate the analytical performances of NRBC enumeration on five top of the range HAs. METHODS: We evaluated the within-run and between-day precision, limit of blank (LoB), limit of detection (LoD), and limit of quantitation (LoQ) of XE-2100 and XN-module (Sysmex), ADVIA 2120i (Siemens), BC-6800 (Mindray), and UniCel DxH 800 (Beckman Coulter). Automated NRBC counts were also compared with optical microscopy (OM). RESULTS: The limits of detection for NRBC of the BC-6800, XN-module, XE-2100, UniCel DxH 800, and ADVIA 2120i are 0.035*109 /L, 0.019*109 /L, 0.067*109 /L, 0.038*109 /L, and 0.167*109 /L, respectively. Our data indicated excellent performance in terms of precision. The agreement with OM was excellent for BC 6800, XN-module, and XE-2100 (Bias 0.023, 0.019, and 0.033*109 /L, respectively). ADVIA 2120i displayed a significant constant error and UniCel DxH 800 both proportional and small constant error. CONCLUSION: Regards to NRBC counting, the performances shown by BC-6800, XN-module, and XE-2100 are excellent also a low count, ADVIA 2120i and UniCel DxH 800 need to be improved. PMID- 28990293 TI - Stigma of mental illness and substance misuse in sub-Saharan African migrants: A qualitative study. AB - Stigma of mental illness and substance misuse can deter help seeking, especially in immigrants who are often reluctant to seek help early for these issues. The aim of the present study was to explore the stigma experience surrounding mental illness and substance misuse, and its implications for improving help seeking, for youths and parents from sub-Saharan African immigrant communities. A qualitative, descriptive design was used. Individual interviews were undertaken with 28 youths, and focus group discussions were held with 41 parents and community leaders in Melbourne, Australia. The findings indicated that public stigma and self-stigma were common and deterred participants' help seeking within sub-Saharan African communities. There was concern about the consequences of disclosure. Personal shame, fear of community rejection, and being labelled a 'lunatic' deterred help seeking. Programmes are needed to address stigma, promote help seeking, and increase mental health knowledge. Mental health nurses and other clinicians in the mental health and alcohol and other drug fields can make an important contribution. Steps are needed to employ more sub-Saharan African immigrant clinicians to help increase help seeking from their communities. PMID- 28990295 TI - Job crafting among health care professionals: The role of work engagement. AB - AIM: The aim of this study was to examine the impact of job crafting on the quality of the work environment of health care professionals. BACKGROUND: Job crafting refers to proactive behavior aimed at optimizing the fit between person and job. Using job demands-resources theory, we hypothesized that job crafting would be positively related to job resources and person-organisation fit, and negatively to hindrance demands. Furthermore, we hypothesized that these relationships would be qualified by work engagement. METHODS: A total of 5,272 health care professionals from one of 35 different organisations filled out an electronic questionnaire (response is 55%). Regression analyses were used to test hypotheses. RESULTS: Consistent with hypotheses, job crafting in the form of increasing job resources was positively related to opportunities for development, performance feedback and P-O fit; and negatively related to hindrance job demands - particularly when work engagement was high. CONCLUSIONS: The combination of job crafting and work engagement is important for the realization of a resourceful work environment and fit between person and organisation. IMPLICATIONS FOR NURSING MANAGEMENT: Interventions aimed at fostering job crafting should be tailored to the motivation of health care professionals. PMID- 28990294 TI - Genetic and molecular risk factors within the newly identified primate-specific exon of the SAP97/DLG1 gene in the 3q29 schizophrenia-associated locus. AB - The synapse-associated protein 97/discs, large homolog 1 of Drosophila (DLG1) gene encodes synaptic scaffold PDZ proteins interacting with ionotropic glutamate receptors including the N-methyl-D-aspartate type glutamate receptor (NMDAR) that is presumed to be hypoactive in brains of patients with schizophrenia. The DLG1 gene resides in the chromosomal position 3q29, the microdeletion of which confers a 40-fold increase in the risk for schizophrenia. In the present study, we performed genetic association analyses for DLG1 gene using a Japanese cohort with 1808 schizophrenia patients and 2170 controls. We detected an association which remained significant after multiple comparison testing between schizophrenia and the single nucleotide polymorphism (SNP) rs3915512 that is located within the newly identified primate-specific exon (exon 3b) of the DLG1 gene and constitutes the exonic splicing enhancer sequence. When stratified by onset age, although it did not survive multiple comparisons, the association was observed in non-early onset schizophrenia, whose onset-age selectivity is consistent with our recent postmortem study demonstrating a decrease in the expression of the DLG1 variant in early-onset schizophrenia. Although the present study did not demonstrate the previously reported association of the SNP rs9843659 by itself, a meta-analysis revealed a significant association between DLG1 gene and schizophrenia. These findings provide a valuable clue for molecular mechanisms on how genetic variations in the primate-specific exon of the gene in the schizophrenia associated 3q29 locus affect its regulation in the glutamate system and lead to the disease onset around a specific stage of brain development. PMID- 28990296 TI - Association between MTHFR microRNA binding site polymorphisms and methotrexate concentrations in Chinese pediatric patients with acute lymphoblastic leukemia. AB - BACKGROUND: The pharmacokinetics and therapeutic response to methotrexate (MTX) display large variability in the treatment of acute lymphoblastic leukemia (ALL). The aim of the present study was to investigate the association of two microRNA (miRNA) binding site polymorphisms (rs3737966 G > A and rs35134728 DEL/TTC) in the 3'-untranslated region of MTHFR with serum MTX concentrations, in a Chinese pediatric population with ALL. METHODS: Genotyping for MTHFR rs3737966 and rs35134728 in 144 children with ALL was performed using the Sequenom MassArray system (Sequenom, San Diego, CA, USA). Serum MTX concentrations were measured by a fluorescence polarization immunoassay 24 h (C24h ) and 42 h (C42h ) after administration. The effects of the polymorphisms on concentration-to-dose (C/D) ratios of MTX were assessed. RESULTS: Complete linkage disequilibrium between rs3737966 and rs35134728 polymorphisms (r2 = 1) was found in the study population. The minor allele frequency observed in the present study (17.4%) was significantly lower than those in European and African samples reported in the 1000 Genomes Project (42.9% and 63.9%, respectively; p < 0.01). The C/D ratios of MTX at 24 and 42 h for the TTC/TTC-A/A haplotype carriers (11.74 and 0.07 MUmol/l per g/m2 , respectively) were significantly lower than those in DEL/DEL-G/G or DEL/TTC-G/G haplotype carriers (12.49 and 0.09 MUmol/l per g/m2 , respectively; p < 0.05). Computational predictions suggested that the two polymorphisms overlapped with putative binding sites of several miRNAs. CONCLUSIONS: The rs3737966 and rs35134728 polymorphisms in MTHFR were associated with serum MTX concentrations. The findings of the present study indicate that miRNAs might be involved in the post-transcriptional regulation of MTHFR. PMID- 28990297 TI - Commentary on Burdzovic Andreas & Bretteville-Jensen (2017): Cannabis use opportunities-an under-researched factor in substance use epidemiology. PMID- 28990298 TI - Commentary on Lichenstein et al. (2017): Escalating cannabis use, weak corticostriatal connections and negative outcomes. PMID- 28990299 TI - Commentary on Parish et al. (2017): What is the best exposure for estimating alcohol-attributable burden of disease? PMID- 28990300 TI - Commentary on Wu et al. (2017): Do very brief reduction interventions increase quitting among smokers not ready to quit? PMID- 28990301 TI - Commentary on McCutcheon et al. (2017): Familial transmission of abstinent remission and social cognition. PMID- 28990302 TI - Commentary on Currie et al. (2017): Low-risk gambling limits-a bridge too far? PMID- 28990304 TI - Commentary on Moore et al. (2017): Focus on policies rather than programmes to address alcohol-related violence. PMID- 28990305 TI - Supporting The SALIS Collection: an ATOD digital archive. PMID- 28990308 TI - Measuring the hierarchical general factor model of psychopathology in young adults. AB - There is evidence that models of psychopathology specifying a general factor and specific second-order factors fit better than competing structural models. Nonetheless, additional tests are needed to examine the generality and boundaries of the general factor model. In a selected second wave of a cohort study, first order dimensions of psychopathology symptoms in 499 23- to 31-year-old twins were analyzed. Using confirmatory factor analysis, a bifactor model specifying a general factor and specific internalizing and externalizing factors fit better than competing models. Factor loadings in this model were sex invariant despite greater variances in the specific internalizing factor among females and greater variances in the general and specific externalizing factors among males. The bifactor structure was robust to the exclusion of any single first-order dimension of psychopathology. Furthermore, the results were essentially unchanged when all overlapping symptoms that define multiple disorders were excluded from symptom dimensions. Furthermore, the best-fitting bifactor model also emerged in exploratory structural equation modeling with freely estimated cross-loadings. The general factor of psychopathology was robust across variations in measurement and analysis. PMID- 28990307 TI - Physiological dead space and arterial carbon dioxide contributions to exercise ventilatory inefficiency in patients with reduced or preserved ejection fraction heart failure. AB - AIMS: Patients with heart failure (HF) with reduced (HFrEF) or preserved (HFpEF) ejection fraction demonstrate an increased ventilatory equivalent for carbon dioxide (VE /VCO2 ) slope. The physiological correlates of the VE /VCO2 slope remain unclear in the two HF phenotypes. We hypothesized that changes in the physiological dead space to tidal volume ratio (VD /VT ) and arterial CO2 tension (PaCO2 ) differentially contribute to the VE /VCO2 slope in HFrEF vs. HFpEF. METHODS AND RESULTS: Adults with HFrEF (n = 32) and HFpEF (n = 27) [mean +/- standard deviation (SD) left ventricular ejection fraction: 22 +/- 7% and 61 +/- 9%, respectively; mean +/- SD body mass index: 28 +/- 4 kg/m2 and 33 +/- 6 kg/m2 , respectively; P < 0.01] performed cardiopulmonary exercise testing with breath by-breath ventilation and gas exchange measurements. PaCO2 was measured via radial arterial catheterization. We calculated the VE /VCO2 slope via linear regression, and VD /VT = 1 - [(863 * VCO2 )/(VE * PaCO2 )]. Resting VD /VT (0.48 +/- 0.08 vs. 0.41 +/- 0.11; P = 0.04), but not PaCO2 (38 +/- 5 mmHg vs. 40 +/- 3 mmHg; P = 0.21) differed between HFrEF and HFpEF. Peak exercise VD /VT (0.39 +/- 0.08 vs. 0.32 +/- 0.12; P = 0.02) and PaCO2 (33 +/- 6 mmHg vs. 38 +/- 4 mmHg; P < 0.01) differed between HFrEF and HFpEF. The VE /VCO2 slope was higher in HFrEF compared with HFpEF (44 +/- 11 vs. 35 +/- 8; P < 0.01). Variance associated with the VE /VCO2 slope in HFrEF and HFpEF was explained by peak exercise VD /VT (R2 = 0.30 and R2 = 0.50, respectively) and PaCO2 (R2 = 0.64 and R2 = 0.28, respectively), but the relative contributions of each differed (all P < 0.01). CONCLUSIONS: Relationships between the VE /VCO2 slope and both VD /VT and PaCO2 are robust, but differ between HFpEF and HFrEF. Increasing VE /VCO2 slope appears to be strongly explained by mechanisms influential in regulating PaCO2 in HFrEF, which contrasts with the strong role of increased VD /VT in HFpEF. PMID- 28990309 TI - Making sense of frailty: An ethnographic study of the experience of older people living with complex health problems. AB - AIM: To explore how older people with complex health problems experience frailty in their daily lives. BACKGROUND: A better understanding of the personal experience of frailty in the context of fluctuating ill-health has the potential to contribute to the development of personalised approaches to care planning and delivery. DESIGN: An ethnographic study of older people, living at home, receiving support from a community matron service in a large city in the North of England. METHODS: Up to six care encounters with each of ten older people, and their community matron, were observed at monthly intervals, over a period of time ranging from 4 to 11 months. Semi-structured interviews were conducted with the older participants in their own homes. Fieldwork took place over a 4-year period. Data analysis was undertaken using the constant comparative method. FINDINGS: The experience of frailty was understood through the construction of four themes: Fluctuating ill-health and the disruption of daily living; Changes to the management of daily living; Frailty as fear, anxiety and uncertainty; Making sense of changes to health and daily living. CONCLUSIONS: Older people work hard to shape and maintain daily routines in the context of complicated and enduring transitions in health and illness. However, they experience episodic moments of frailty, often articulated as uncertainty, where daily living becomes precarious and their resilience is threatened. Developing an understanding of the personal experiences of frail older people in the context of transition has the potential to inform nursing practice in person-centred care . IMPLICATIONS FOR PRACTICE: Nurses need to support frail older people to maintain independence and continuity of personhood in the context of daily routines. PMID- 28990310 TI - The interaction between vitamin D receptor polymorphisms and sun exposure around time of diagnosis influences melanoma survival. AB - Evidence on the relationship between the vitamin D pathway and outcomes in melanoma is growing, although it is not always clear. We investigated the impact of measured levels of sun exposure at diagnosis on associations of vitamin D receptor gene (VDR) polymorphisms and melanoma death in 3336 incident primary melanoma cases. Interactions between six SNPs and a common 3'-end haplotype were significant (p < .05). These SNPs, and a haplotype, had a statistically significant association with survival among subjects exposed to high UVB in multivariable regression models and exerted their effect in the opposite direction among those with low UVB. SNPs rs1544410/BsmI and rs731236/TaqI remained significant after adjustment for multiple testing. These results suggest that the association between VDR and melanoma-specific survival is modified by sun exposure around diagnosis, and require validation in an independent study. Whether the observed effects are dependent or independent of vitamin D activation remains to be determined. PMID- 28990311 TI - Comprehensive data of 3,820 patients newly diagnosed with colorectal liver metastasis between 2005 and 2007: report of a nationwide survey in Japan. AB - To collect big data for further research to improve treatment outcomes in patients with colorectal liver metastasis (CRLM), the Joint Committee for Nationwide Survey on CRLM was established by the Japanese Society for Cancer of the Colon and Rectum and the Japanese Society of Hepato-Biliary-Pancreatic Surgery. The joint committee initiated data collection since 2014. The data of 4,237 patients newly diagnosed with CRLM between 2005 and 2007 were registered from 134 departments of 127 institutions (64%) among 209 departments (from 201 institutions) that agreed to participate in this study. Finally, 3,820 patients were enrolled in this report after a quality management process by the joint committee. We report the comprehensive data obtained from 3,820 patients, clinicopathological findings, treatment strategies, prognoses, and implementation status of chemotherapy. The joint committee is prospectively collecting data of patients newly diagnosed with CRLM after 2013 and will provide these raw data, including data of patients diagnosed between 2005 and 2007, to researchers who will conduct meaningful studies that meet the aim of the joint committee. PMID- 28990313 TI - In vitro variations of Mean platelet volume over time in blood samples collected in different anticoagulants from thrombocytopenic patients and healthy subjects. PMID- 28990314 TI - Female breast cancer management and survival: The experience of major public hospitals in South Australia over 3 decades-trends by age and in the elderly. AB - BACKGROUND: Clinical registry data from major South Australian public hospitals were used to investigate trends in invasive breast-cancer treatment and survival by age. METHODS: Disease-specific survival was calculated for the 1980 to 2013 diagnostic period using Kaplan-Meier product-limit estimates, with a censoring of live cases on December 31, 2014. Cox proportional hazards regression was used to examine differences in survival by age and tumour characteristic. First-round treatments following diagnosis were analysed, using multiple logistic regression to adjust for confounding. RESULTS: Five-year survival increased from 75% in the 1980s to 87% in 2000 to 2013, consistent with national trends, and with increases occurring irrespective of age. There was an increased use of breast conserving surgery, radiotherapy, chemotherapy, and hormone treatments. Five-year survival was lower for women aged 80+ years, increasing from 65% in the 1980s to 74% in 2000 to 2013. Lower survival in these older women persisted after adjusting for TNM stage, other clinical variables, and diagnostic year, without evidence of a reduced disparity over time. Older women were less likely to have surgery, radiotherapy, and chemotherapy throughout 1980 to 2013. By comparison, their use of hormone therapy was elevated. The adjusted relative odds of mastectomy (as opposed to breast conserving surgery) were lower for the 80+ year age range. CONCLUSIONS: Breast-cancer survival increases applied to all ages, including 80+ years, but poorer outcomes persisted in this older group and the gap did not reduce. A key question is whether the best trade-off now exists between optimally therapeutic cancer treatment and accommodations for frailty and co-morbidity in the aged, or whether opportunities exist for better trade-offs and better survival. Local registry data are important for describing local service activity and outcomes by age for local service providers, health administrations and consumer groups; monitoring disparities; and indicating effects of local initiatives. PMID- 28990315 TI - Psychometric validation of a new measurement instrument for time-oriented patient information in electronic medical records: A questionnaire survey of physicians. AB - RATIONALE, AIMS, AND OBJECTIVES: Time is an important element in medical data. Physicians record and store information about patients' disease progress and treatment response in electronic medical records (EMRs). Because EMRs use timestamps, physicians can identify patterns over time regarding a patient's disease and treatment (eg, laboratory values and medications). However, analyses of physicians' use and satisfaction with EMRs have focused on functionality, storage, and system operation rather than the use of time-oriented information. This study aimed to understand physicians' needs regarding time-oriented patient information in EMRs in clinical practice. METHODS: The reliability and validity of the items in the questionnaire were evaluated in 87 physicians at a national university hospital. Internal consistency was satisfactory (Cronbach alpha coefficient, 0.87). RESULTS: Four dimensions were identified in exploratory factor analysis. Correlations between the 4 dimensions supported the construct validity of the items. Scores of time-oriented patients' medical history in the 4 dimensions showed a significant association with physician age. Based on confirmatory factor analysis, associations were significant and positive (P < .001). In terms of the needs of physicians regarding time-oriented patient information in EMRs, both time-oriented treatment results followed by time oriented team information had significant positive associations. CONCLUSION: Our study suggests that 4 specific time-oriented patient information factors in EMRs are needed by physicians. Exploring physicians' needs regarding patient-specific time-oriented information may provide a better understanding of the barriers facing the adoption and use of EMRs (eg, decision-making and practice safety concerns) and lead to better acceptance of EMRs in physicians' clinical practices. PMID- 28990316 TI - Non-invasive assessment of left ventricular filling pressure. AB - Dyspnoea is a presenting symptom for patients with heart failure. It is often due to elevated left ventricular (LV) filling pressure but can be due to pulmonary disease or other non-cardiac reasons. While physical examination is useful, it has its limitations. Accordingly, non-invasive imaging has an important role in the diagnostic evaluation of patients with known or suspected heart failure. Echocardiography is usually the first test obtained and is used to determine LV volumes, ejection fraction and mass as well as right ventricular size and function, left and right atrial volumes, valvular lesions, and pulmonary artery pressures. Additionally, LV filling pressure can be estimated. A recent algorithm was published that depends on clinical, two-dimensional data and Doppler signals. The algorithm is accurate in patients with depressed and normal ejection fraction. There are other measurements that can be obtained as LV strain and diastolic strain rate and left atrial strain. These indices provide valuable insight into LV relaxation and filling pressure as well as left atrial function. Assessment of LV filling pressure has been evaluated most extensively in patients in sinus rhythm. However, it is also possible to assess LV filling and draw inferences about LV filling pressure in patients in atrial fibrillation, in patients with mitral valve disease and in patients with left ventricular assist devices. Left ventricular filling has been assessed by other imaging modalities, including cardiac computed tomography and cardiac magnetic resonance. While these other imaging modalities may be needed in some cases, echocardiography has the highest feasibility and validation, and the most practical application. PMID- 28990317 TI - An in vitro and in vivo characterization of fine WE43B magnesium wire with varied thermomechanical processing conditions. AB - Absorbable implants made of magnesium alloys may revolutionize surgical intervention, and fine magnesium wire will be critical to many applications. Functionally, the wires must have sufficient mechanical properties to withstand implantation and in-service loading, have excellent tissue tolerance, and exhibit an appropriate degradation rate for the application. Alloy chemistry and thermomechanical processing conditions will significantly impact the material's functional performance, but the exact translation of these parameters to implant performance is unclear. With this in mind, fine (127 um) WE43B magnesium alloy wires in five thermomechanical process (TMP) conditions (90% cold work [CW], and 250, 375, 400, and 450 degrees C heat treatments) were investigated for their effect on mechanical and corrosion behavior. The TMP conditions gave clear metallurgical differences: transverse grain dimensions ranged from 200 nm (CW) to 3 um (450 degrees C), UTS varied from 324 MPa (450 degrees C) to 608 MPa (250 degrees C), and surgical knotting showed some were suitable (CW, 400 degrees C, 450 degrees C) while others were not (250 degrees C, 350 degrees C). In vitro and in vivo corrosion testing yielded interesting and in some cases conflicting results. After 1 month immersion in cell culture medium, wire corrosion was extensive, and TMP conditions altered the macrocorrosion morphology but not the rate or total release of magnesium ions. After 1 month subdermal implantation in mice, all wires were well tolerated and showed very little corrosion (per uCT and histology), but differences in localized corrosion were detected between conditions. This study indicates that WE43B wires treated at 450 degrees C may be most suitable for surgical knotting procedures. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1987-1997, 2018. PMID- 28990318 TI - Depression hurts, depression costs: The medical spending attributable to depression and depressive symptoms in China. AB - Due to its fast economic growth and lifestyle changes, China is experiencing a rapid epidemiological transition from communicable to noncommunicable diseases (NCDs). Mental disorder such as depression is an important yet often neglected NCD and is becoming a growing cause of disability, suicides, and disease burden. This paper provides the first nationally representative estimate of the medical cost attributable to depression and depressive symptoms among the adult population in China. On the basis of the 2012 China Family Panel Studies survey, our results indicate that these mental health conditions have significant impacts on the individual medical expenditure, and they jointly contribute to 14.7% of total personal expected medical spending in China, with depression and depressive symptoms accounting for 6.9% and 7.8%, respectively. Given that patients with mental illness face multiple psychological and institutional barriers in seeking appropriate treatment, the high depression-induced medical costs may be primarily driven by the cost-shifting effect from mental health care to general health care, as mental disorders often coexist with other NCDs such as diabetes and hypertension. As an implication, our study calls for an urgent reform of China's mental health and insurance systems to remove the policy-induced obstacles for the access to mental health care resources. PMID- 28990312 TI - Cyclic-di-GMP regulation of virulence in bacterial pathogens. AB - Signaling pathways allow bacteria to adapt to changing environments. For pathogenic bacteria, signaling pathways allow for timely expression of virulence factors and the repression of antivirulence factors within the mammalian host. As the bacteria exit the mammalian host, signaling pathways enable the expression of factors promoting survival in the environment and/or nonmammalian hosts. One such signaling pathway uses the dinucleotide cyclic-di-GMP (c-di-GMP), and many bacterial genomes encode numerous proteins that are responsible for synthesizing and degrading c-di-GMP. Once made, c-di-GMP binds to individual protein and RNA receptors to allosterically alter the macromolecule function to drive phenotypic changes. Each bacterial genome encodes unique sets of genes for c-di-GMP signaling and virulence factors so the regulation by c-di-GMP is organism specific. Recent works have pointed to evidence that c-di-GMP regulates virulence in different bacterial pathogens of mammalian hosts. In this review, we discuss the criteria for determining the contribution of signaling nucleotides to pathogenesis using a well-characterized signaling nucleotide, cyclic AMP (cAMP), in Pseudomonas aeruginosa. Using these criteria, we review the roles of c-di-GMP in mediating virulence and highlight common themes that exist among eight diverse pathogens that cause different diseases through different routes of infection and transmission. WIREs RNA 2018, 9:e1454. doi: 10.1002/wrna.1454 This article is categorized under: RNA in Disease and Development > RNA in Disease. PMID- 28990319 TI - A qualitative study on community pharmacists' decision-making process when making a diagnosis. AB - RATIONALE, AIMS, AND OBJECTIVES: Self-care policies are increasingly directing patients to seek advice from community pharmacists. This means pharmacists need to have sound diagnostic decision-making skills to enable them to recognise a variety of conditions. The aim of this study was to investigate the process by which pharmacists manage patient signs and symptoms and to explore their use of decision-making for diagnostic purposes. METHODS: Data were collected through semi-structured, face-to-face interviews with community pharmacists working in England, between August 2013 and November 2014. Pharmacists were asked to share their experiences on how they performed patient consultations, and more specifically how they would approach a hypothetical headache scenario. As part of the interview, their sources of knowledge and experience were also explored. Framework analysis was used to identify themes and subthemes. RESULTS: Eight interviews were conducted with pharmacists who had a wide range of working practice, from 1 year through to 40 years of experience. The pharmacists' main motivations during consultations were product selection and risk minimisation. Their questioning approach and decision-making relied heavily on mnemonic methods. This led to poor quality information gathering-although pharmacists acknowledged they needed to "delve deeper" but were often unable to articulate how or why. Some pharmacists exhibited elements of clinical reasoning in their consultations, but this seemed, mostly, to be unconscious and subsequently applied inappropriately. Overall, pharmacists exhibited poor decision-making ability, and often decisions were based on personal belief and experiences rather than evidence. CONCLUSIONS: Community pharmacists relied heavily on mnemonic methods to manage patients' signs and symptoms with diagnosis-based decision making being seldom employed. These findings suggest practicing pharmacists should receive more diagnostic training. PMID- 28990320 TI - Non-Tuberculosis mycobacterium speciation using HPLC under Revised National TB Control Programme (RNTCP) in India. AB - AIMS: Non-Tuberculous Mycobacteria (NTM) are ubiquitous in nature. The data on prevalence of NTM under the RNTCP is scarce. Many NTM species have clinical significance, and hence their identification and speciation are important. METHODS AND RESULTS: It is a cross-sectional study conducted at the five RNTCP accredited culture and drug susceptibility testing (CDST) laboratory. The culture isolates from AFB positive but Immunochromatographic test negative samples were taken for identification and speciation using HPLC. Of the total 266 isolates only 164 isolates had a second sample received at the laboratory. The speciation was done using HPLC for those isolates. The type of species identified are: 26.8% (44) were Mycobacterium chelonae, 12.8% (21) were Mycobacterium fortuitum, 9% (15) were Mycobacterium gordonae, 9% (15) were Mycobacterium tuberculosis complex, 6.1% (10) were Mycobacterium kansasii, 4.9% (8) were Mycobacterium simiae, 2.4% (4) were Mycobacterium thermophile, 1.2% (2) were Mycobacterium gastri, 0.6% (1) were Mycobacterium scrofulaceum, 0.6% (1) were Mycobacterium avium and 4.9% (8) isolates had chromatogram which was un-interpretable. CONCLUSION: Identification and its speciation of NTM are not routinely done under TB control programme. Since HPLC could identify 95% of isolates belonging to 10 species, the speciation of NTM using HPLC should gain importance in the diagnosis of disease caused by NTM. SIGNIFICANCE AND IMPACT OF STUDY: NTM are emerging as important causative agents of pulmonary and extra pulmonary disease, the ability to recognize disease caused by NTM and subsequently treat such disease has become increasingly important. The identification of NTM up to its species level should gain importance in all TB reference Laboratories. PMID- 28990321 TI - Ecological and evolutionary legacy of megafauna extinctions. AB - For hundreds of millions of years, large vertebrates (megafauna) have inhabited most of the ecosystems on our planet. During the late Quaternary, notably during the Late Pleistocene and the early Holocene, Earth experienced a rapid extinction of large, terrestrial vertebrates. While much attention has been paid to understanding the causes of this massive megafauna extinction, less attention has been given to understanding the impacts of loss of megafauna on other organisms with whom they interacted. In this review, we discuss how the loss of megafauna disrupted and reshaped ecological interactions, and explore the ecological consequences of the ongoing decline of large vertebrates. Numerous late Quaternary extinct species of predators, parasites, commensals and mutualistic partners were associated with megafauna and were probably lost due to their strict dependence upon them (co-extinctions). Moreover, many extant species have megafauna-adapted traits that provided evolutionary benefits under past megafauna rich conditions, but are now of no or limited use (anachronisms). Morphological evolution and behavioural changes allowed some of these species partially to overcome the absence of megafauna. Although the extinction of megafauna led to a number of co-extinction events, several species that likely co-evolved with megafauna established new interactions with humans and their domestic animals. Species that were highly specialized in interactions with megafauna, such as large predators, specialized parasites, and large commensalists (e.g. scavengers, dung beetles), and could not adapt to new hosts or prey were more likely to die out. Partners that were less megafauna dependent persisted because of behavioural plasticity or by shifting their dependency to humans via domestication, facilitation or pathogen spill-over, or through interactions with domestic megafauna. We argue that the ongoing extinction of the extant megafauna in the Anthropocene will catalyse another wave of co-extinctions due to the enormous diversity of key ecological interactions and functional roles provided by the megafauna. PMID- 28990322 TI - Proteogenomics Gets onto the Regulation of mRNA Decoding and Translation into Protein. AB - Proteogenomics, the integrative analysis of the proteome and the genome, increasingly provides protein-level insights about the regulation of gene expression and protein translation. Armengaud et al. (Proteomics 2017, 17, 1700211) nicely illustrate this trend with the first in-depth proteomic analysis of the eukaryotic and unicellular intestinal parasite Blastocystis sp. Not only this work constitutes an important milestone toward the proteogenomics profile of this human pathogen, but also it demonstrates at the protein level the occurrence of a specific mechanism of mRNA decoding. GU-rich motifs located downstream of mRNA polyadenylation sites create termination codons that ultimately result in the synthesis of proteins with lower molecular weight than predicted from gene sequence. Thus, the scope of proteogenomics now extends to the regulation of mRNA translation into proteins, providing a proof of concept for future studies in multicellular eukaryotes such as humans and plants. PMID- 28990323 TI - Multiple growth periods predict unfavourable pathology in patients with small renal masses. AB - OBJECTIVE: To use the number of positive growth periods as a characterization of the growth of small renal masses in order to determine potential predictors of malignancy. PATIENTS AND METHODS: Patients who underwent axial imaging at multiple time points prior to surgical resection for a small renal mass were queried. Patients were categorized based on their pathological tumour grade and stage: favourable (benign, chromophobe and low-grade pT1-2 renal cell carcinoma [RCC]) vs unfavourable (high-grade of any stage and low-grade pT3-4 RCC). A positive growth period was counted each time the difference in greatest tumour diameters between two images was positive. The Cochran-Armitage trend test and Somers' D association were used to determine if the number of positive growth periods was correlated with unfavourable pathology. RESULTS: Of the 124 patients, 86 (69.4%) had favourable pathology and 38 (30.6%) had unfavourable pathology. Those who had favourable pathology were younger than those who had unfavourable pathology: median (interquartile range [IQR]) 61.0 (52.2-66.0) vs 68.5 (61.5 77.0); P < 0.001. The overall growth rate was higher in the unfavourable group, but was not statistically significant: mean (sd) 0.7 (1.7) vs 1.6 (2.8) cm/year; P = 0.07. There was a significant trend difference in the number of positive growth periods between favourability groups (P = 0.02). An association between increased number of positive growth periods and unfavourable pathology was observed: 0.15 (95% confidence interval 0.02, 0.29). The ratios of favourable to unfavourable pathology were 1.8, 1.0, 0.66, 0.59 and 0 as the number of positive growth periods increased from 0 to 4, respectively. CONCLUSION: While overall growth rate was not predictive of pathology favourability, there was a positive association between the number of positive growth periods and unfavourable pathology. The number of positive growth periods may be a potential parameter for malignant potential in patients undergoing active surveillance for small renal masses. PMID- 28990325 TI - Predominance of neutrophils in the cerebrospinal fluid of patients treated with intravenous immunoglobulin. AB - Patients treated with intravenous immunoglobulin can present with numerous neutrophils in the cerebrospinal fluid. PMID- 28990324 TI - Involvement of stanniocalcins in the deregulation of glycaemia in obese mice and type 2 diabetic patients. AB - Stanniocalcins are expressed in the pancreas tissue, and it was suggested a direct correlation between circulating insulin and STC2 concentrations in human. Here, we show a significant correlation between STC1 and both glycaemia and glycosylated haemoglobin among DM2 patients, while DM2 patients who present the greatest glycosylated haemoglobin values exhibited the lowest STC2 expression. However, treatment of patients with antiglycaemic drugs does not significantly modify the expression of both STCs. On the other hand, STC2-/- mice that exhibited neonatal and adult overweight further presented deregulated glycaemia when they were feed with a hypercaloric diet (breeding pellet, BP). This alteration is more evident at the early stages of the animal life. Deregulated glycaemia in these mice was confirmed using glucose oral test. In addition, STC2 /- mice present enhanced pancreas size; thus, the histological analysis reveals that WT mice respond to BP diet by increasing the size of the pancreatic islets through inducing cell division, and STC2-/- mice lack this compensatory mechanism. Contrary, BP fed STC2-/- mice show enhanced number of islets but of similar size than those fed with regular pellet. Histopathological analysis demonstrates tissue structure disruption and erythrocytes infiltrations in STC2-/ mice, possibly due to the stress evoked by the BP diet. Finally, enhanced glucagon immunostaining was observed in the islet of STC2-/- mice, and the glucagon ELISA assay confirmed the increase in the circulating glucagon. Summarizing, we present evidence of the role of STCs, mainly STC2, as a possible early marker during development of diabetes mellitus. PMID- 28990327 TI - The Recent Crystal Structure of Human Tyrosinase Related Protein 1 (HsTYRP1) Solves an Old Problem and Poses a New One. AB - Show your metal: l-Tyrosine is converted into the protective antioxidative polymer melanin in a sequence of reactions. In humans, the catalytic pathway starts with the tyrosinase HsTYR and two tyrosinase-related proteins HsTYRP1 and HsTYRP2. All three enzymes have the same active site but the latter two contain two zinc ions instead of copper ions. PMID- 28990326 TI - Association of the nurse work environment with nurse incivility in hospitals. AB - AIM: To determine whether nurse coworker incivility is associated with the nurse work environment, defined as organisational characteristics that promote nurse autonomy. BACKGROUND: Workplace incivility can negatively affect nurses, hospitals and patients. Plentiful evidence documents that nurses working in better nurse work environments have improved job and health outcomes. There is minimal knowledge about how nurse coworker incivility relates to the United States nurse work environment. METHODS: Quantitative, cross-sectional. Data were collected through online surveys of registered nurses in a southwestern United States health system. The survey content included the National Quality Forum endorsed Practice Environment Scale of the Nursing Work Index and the Workplace Incivility Scale. Data analyses were descriptive and correlational. RESULTS: Mean levels of incivility were low in this sample of 233 staff nurses. Incivility occurred 'sporadically' (mean = 0.58; range 0.00-5.29). The nurse work environment was rated highly (mean = 3.10; range of 1.00-4.00). The nurse work environment was significantly inversely associated with coworker incivility. The nurse manager qualities were the principal factor of the nurse work environment associated with incivility. CONCLUSIONS: Supportive nurse managers reduce coworker incivility. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse managers can shape nurse work environments to prevent nurse incivility. PMID- 28990328 TI - A striking case of dermatosis neglecta. PMID- 28990329 TI - Educators' emotion regulation strategies and their physiological indicators of chronic stress over 1 year. AB - Studies show teaching is a highly stressful profession and that chronic work stress is associated with adverse health outcomes. This study analysed physiological markers of stress and self-reported emotion regulation strategies in a group of middle school teachers over 1 year. Chronic physiological stress was assessed with diurnal cortisol measures at three time points over 1 year (fall, spring, fall). The aim of this longitudinal study was to investigate the changes in educators' physiological level of stress. Results indicate that compared to those in the fall, cortisol awakening responses were blunted in the spring. Further, this effect was ameliorated by the summer break. Additionally, self-reported use of the emotion regulation strategy reappraisal buffered the observed blunting that occurred in the spring. PMID- 28990331 TI - Antimalarial and Antileishmanial Activities of Phytophenolics and Their Synthetic Analogues. AB - Thirty-seven phytophenolics and their synthetic analogues were evaluated for activity against two protozoal pathogens, Leishmania donovani and Plasmodium falciparum (D6 and W2 clones), respectively. 4,6-Dimethoxyaurone demonstrated the highest activity with IC50 values of 13.2 and 16.9 MUm against L. donovani and P. falciparum (W2 clone), respectively, without undesired cytotoxicity against VERO cells. The moiety having two benzene rings was critical to maintain the antiprotozoal activities based on the observation that both coumaranones and chromones were inactive while other test compounds, including coumarans and aurones, remained active. There was no correlation between antiprotozoal activities and previously evaluated insect antifeedant activity against common cutworms (Spodoptera litura). Flavonoids, including aurones, pterocarpans, and lignan like dihydrobenzofurans, structural analogues of coumarans, are abundant in fruits and vegetables, so these phytophenolics may act as natural antiprotozoal agents in humans. PMID- 28990332 TI - The expression and functional activities of smooth muscle myosin and non-muscle myosin isoforms in rat prostate. AB - Benign prostatic hyperplasia (BPH) is mainly caused by increased prostatic smooth muscle (SM) tone and volume. SM myosin (SMM) and non-muscle myosin (NMM) play important roles in mediating SM tone and cell proliferation, but these molecules have been less studied in the prostate. Rat prostate and cultured primary human prostate SM and epithelial cells were utilized. In vitro organ bath studies were performed to explore contractility of rat prostate. SMM isoforms, including SM myosin heavy chain (MHC) isoforms (SM1/2 and SM-A/B) and myosin light chain 17 isoforms (LC17a/b ), and isoform ratios were determined via competitive RT-PCR. SM MHC and NM MHC isoforms (NMMHC-A, NMMHC-B and NMMHC-C) were further analysed via Western blotting and immunofluorescence microscopy. Prostatic SM generated significant force induced by phenylephrine with an intermediate tonicity between phasic bladder and tonic aorta type contractility. Correlating with this kind of intermediate tonicity, rat prostate mainly expressed LC17a and SM1 but with relatively equal expression of SM-A/SM-B at the mRNA level. Meanwhile, isoforms of NMMHC-A, B, C were also abundantly present in rat prostate with SMM present only in the stroma, while NMMHC-A, B, C were present both in the stroma and endothelial. Additionally, the SMM selective inhibitor blebbistatin could potently relax phenylephrine pre-contracted prostate SM. In conclusion, our novel data demonstrated the expression and functional activities of SMM and NMM isoforms in the rat prostate. It is suggested that the isoforms of SMM and NMM could play important roles in BPH development and bladder outlet obstruction. PMID- 28990333 TI - A truly complementary approach: A qualitative exploration of complementary and alternative medicine practitioners' views of treating ankylosing spondylitis. AB - OBJECTIVE: Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease in which individuals experience a long delay to diagnosis. Prior to diagnosis, individuals report frequent use of complementary and alternative medicine (CAM) therapies. While popularly used, there is a dearth of knowledge concerning the experiences of CAM practitioners in terms of treating individuals with AS. Addressing this knowledge gap, the present study provides a detailed exploration of how UK-based CAM practitioners treat individuals with AS. METHODS: Semi-structured telephone interviews were conducted with eight UK-based CAM practitioners, (four males), aged 45-69 years. CAM practitioners were recruited across a range of CAM therapies and years of CAM practice experience (8-46 years). RESULTS: Thematic analysis resulted in the identification of three themes to characterize the data. Themes comprised: (i) the whole picture; (ii) alarm bells; and (iii) a common language. Themes highlighted CAM practitioner adoption of a holistic, yet individualized approach to treating individuals with AS, despite a general sense of lack of knowledge concerning AS among CAM practitioners. Notably, results indicated a desire of CAM practitioners to work more collaboratively with mainstream health providers to provide more joined-up care for individuals with AS. CONCLUSION: CAM practitioners emphasized the benefits of CAM to focus on providing effective symptom management when used in conjunction, rather than in opposition to, mainstream healthcare. Adoption of a more holistic approach to AS management by CAM practitioners may empower clients to become more aware of symptoms, thus potentially reducing delays in receiving a formal diagnosis of AS. PMID- 28990334 TI - What's Next for Acute Heart Failure Research? AB - Each year over one million patients with acute heart failure (AHF) present to a United States emergency department (ED). The vast majority are hospitalized for further management. The length of stay and high postdischarge event rate in this cohort have changed little over the past decade. Therapeutic trials have failed to yield substantive improvement in postdischarge outcomes; subsequently, AHF care has changed little in the past 40 years. Prior research studies have been fragmented as either "inpatient" or "ED-based." Recognizing the challenges in identification and enrollment of ED patients with AHF, and the lack of robust evidence to guide management, an AHF clinical trials network was developed. This network has demonstrated, through organized collaboration between cardiology and emergency medicine, that many of the hurdles in AHF research can be overcome. The development of a network that supports the collaboration of acute care and HF researchers, combined with the availability of federally funded infrastructure, will facilitate more efficient conduct of both explanatory and pragmatic trials in AHF. Yet many important questions remain, and in this document our group of emergency medicine and cardiology investigators have identified four high priority research areas. PMID- 28990335 TI - Next-Generation Magnetic Nanocomposites: Cytotoxic and Genotoxic Effects of Coated and Uncoated Ferric Cobalt Boron (FeCoB) Nanoparticles In Vitro. AB - Metal nanoparticles (NPs) have unique physicochemical properties and a widespread application scope depending on their composition and surface characteristics. Potential biomedical applications and the growing diversity of novel nanocomposites highlight the need for toxicological hazard assessment of next generation magnetic nanomaterials. Our study aimed to evaluate the cytotoxic and genotoxic properties of coated and uncoated ferric cobalt boron (FeCoB) NPs (5-15 nm particle size) in cultured normal human dermal fibroblasts. Cell proliferation was assessed via ATP bioluminescence kit, and DNA breakage and chromosomal damage were measured by alkaline comet assay and micronucleus test. Polyacryl acid coated FeCoB NPs [polyacrylic acid (PAA)-FeCoB NPs) and uncoated FeCoB NPs inhibited cell proliferation at 10 MUg/ml. DNA strand breaks were significantly increased by PAA-coated FeCoB NPs, uncoated FeCoB NPs and l-cysteine-coated FeCoB NPs (Cys-FeCoB NPs), although high concentrations (10 MUg/ml) of coated NPs (Cys- and PAA-FeCoB NPs) showed significantly more DNA breakage when compared to uncoated ones. Uncoated FeCoB NPs and coated NPs (PAA-FeCoB NPs) also induced the formation of micronuclei. Additionally, PAA-coated NPs and uncoated FeCoB NPs showed a negative correlation between cell proliferation and DNA strand breaks, suggesting a common pathomechanism, possibly by oxidation-induced DNA damage. We conclude that uncoated FeCoB NPs are cytotoxic and genotoxic at in vitro conditions. Surface coating of FeCoB NPs with Cys and PAA does not prevent but rather aggravates DNA damage. Further safety assessment and a well-considered choice of surface coating are needed prior to application of FeCoB nanocomposites in biomedicine. PMID- 28990336 TI - Peer teaching of the physical exam: a pilot study. AB - BACKGROUND: Mastery of the physical exam (PE), and the ability to teach it to peers and medical students, are important milestones for residents (junior doctors); however, several reports indicate that PE skills are in decline. To address this need, we explored the use of peer observation of teaching (POT) as a conceptual framework to develop an innovative approach to PE teaching at the postgraduate medical education level. INNOVATION: We designed a PE POT session to be conducted at the patient bedside, and piloted four sessions in April 2014. Sessions involved a senior medicine resident teaching a focused PE to their team (consisting of two postgraduate first-year residents), while being observed by a peer, followed by feedback anchored in 11 validated measures of clinical teaching. The sessions were completed in 30-35 minutes and were enthusiastically received by residents. Participants valued the interactive approach and the opportunity to exchange feedback with a peer on their PE teaching skills. IMPLICATIONS: This pilot using POT methodology to teach the PE addressed mandatory core competencies related to patient care and practice-based learning and improvement. Residents gained insights on their PE teaching skills while interacting with their peers in a novel and reciprocal learning opportunity. This experience helped participants to value their role as PE teachers and generate strategies to change their teaching behaviours. Despite this being a small study, POT offers an innovative approach to teach the PE at the postgraduate level, with the potential to address the gap of PE teaching and learning. Several reports indicate that physical exam skills are in decline. PMID- 28990337 TI - The prioritization of symptom beliefs over illness beliefs: The development and validation of the Pain Perception Questionnaire for Young People. AB - OBJECTIVES: To investigate the suitability of the revised Illness Perception Questionnaire (IPQ-R) for use with adolescents with a long-term pain condition and to validate a new questionnaire for use with this age group. DESIGN: A three phase mixed-methods study. METHODS: Phase 1 comprised in-depth qualitative analyses of audio-recorded cognitive interviews with 20 adolescents with juvenile idiopathic arthritis who were answering IPQ-R items. Transcripts were coded using framework analysis. A content analysis of their intended responses to individual items was also conducted. In Phase 2, a new questionnaire was developed and its linguistic and face validity were assessed with 18 adolescents without long-term conditions. In Phase 3, the construct validity of the new questionnaire was assessed with 240 adolescents with juvenile idiopathic arthritis. A subset of 43 adolescents completed the questionnaire a second time to assess test-retest reliability. All participants were aged 11-16 years. RESULTS: Participants described both conceptual and response format difficulties when answering IPQ-R items. In response, the Pain Perception Questionnaire for Young People (PPQ-YP) was designed which incorporated significant modifications to both wording and response formats when compared with the IPQ-R. A principal component analysis of the PPQ-YP identified ten constructs in the new questionnaire. Emotional representations were separated into two constructs, responsive and anticipatory emotions. The PPQ-YP showed high test-retest reliability. CONCLUSIONS: Symptom beliefs appear to be more salient to adolescents with a long-term pain condition than beliefs about the illness as a whole. A new questionnaire to assess pain beliefs of adolescents was designed. Further validation work may be needed to assess its suitability for use with other pain conditions. Statement of contribution What is already known on this subject? Versions of the adult Revised Illness Perception Questionnaire (IPQ-R) have been adapted for adolescents and children by changing item wording; however, research to assess the degree to which the underlying IPQ-R constructs are relevant to adolescents with a long term condition had not been performed. What the present study adds? In adolescents, beliefs about symptoms of their condition are more salient than beliefs about the illness as a whole. Question response formats for children and young people need to take account of age-specific abilities. A new questionnaire has been designed for adolescents with pain. It is theoretically congruent with the CS-SRM. PMID- 28990340 TI - Mechanical thrombectomy revisited is there any value? AB - The use of mechanical thrombectomy in STEMI with large amount of jeopardized myocardium may preserve regional wall motion When appropriate and done with proper removal technique, there does not appear to be any increased incidence of neurologic complications The guideline recommendation that mechanical thrombectomy should not be done routinely is supported by these authors. PMID- 28990338 TI - Minor Structural Variations of Small Molecules Tune Regulatory Activities toward Pathological Factors in Alzheimer's Disease. AB - Chemical tools have been valuable for establishing a better understanding of the relationships between metal ion dyshomeostasis, the abnormal aggregation and accumulation of amyloid-beta (Abeta), and oxidative stress in Alzheimer's disease (AD). Still, very little information is available to correlate the structures of chemical tools with specific reactivities used to uncover such relationships. Recently, slight structural variations to the framework of a chemical tool were found to drastically determine the tool's reactivities toward multiple pathological facets to various extents. Herein, we report our rational design and characterization of a structural series to illustrate the extent to which the reactivities of small molecules vary toward different targets as a result of minor structural modifications. These compounds were rationally and systematically modified based on consideration of properties, including ionization potentials and metal binding, to afford their desired reactivities with metal-free or metal-bound Abeta, reactive oxygen species (ROS), and free organic radicals. Our results show that although small molecules are structurally similar, they can interact with multiple factors associated with AD pathogenesis and alleviate their reactivities to different degrees. Together, our studies demonstrate the rational structure-directed design that can be used to develop chemical tools capable of regulating individual or interrelated pathological features in AD. PMID- 28990341 TI - Patterns of restenosis for the SFA: The second step on a long journey. AB - Restenosis patterns required better definitions Defining restenosis patterns may help compare technologies better Further research with consistent restenosis pattern definition will help us define the most value-added treatments. PMID- 28990342 TI - Post-TAVR aortogram: Transform it into a modern tool for prognosis and efficiency. AB - Video densitometry after aortography can provide objective assessment of aortic regurgitation post-transcatheter aortic valve replacement (TAVR) Contrast density ratio between the left ventricular outflow track and proximal aorta (LVOT-AR) of >0.17 suggests greater than mild aortic insufficiency and correlates with echo findings LVOT-AR of >0.17 is associated with higher 30-day and 1-year mortality. PMID- 28990339 TI - The antiviral effects of RSV fusion inhibitor, MDT-637, on clinical isolates, vs its achievable concentrations in the human respiratory tract and comparison to ribavirin. AB - BACKGROUND: Respiratory syncytial virus (RSV) viral load and disease severity associate, and the timing of viral load and disease run in parallel. An antiviral must be broadly effective against the natural spectrum of RSV genotypes and must attain concentrations capable of inhibiting viral replication within the human respiratory tract. OBJECTIVES: We evaluated a novel RSV fusion inhibitor, MDT 637, and compared it with ribavirin for therapeutic effect in vitro to identify relative therapeutic doses achievable in humans. METHOD: MDT-637 and ribavirin were co-incubated with RSV in HEp-2 cells. Quantitative PCR assessed viral concentrations; 50% inhibitory concentrations (IC50 ) were compared to achievable human MDT-637 and ribavirin peak and trough concentrations. RESULTS AND CONCLUSIONS: The IC50 for MDT-637 and ribavirin (against RSV-A Long) was 1.42 and 16 973 ng/mL, respectively. The ratio of achievable peak respiratory secretion concentration to IC50 was 6041-fold for MDT-637 and 25-fold for aerosolized ribavirin. The ratio of trough concentration to IC50 was 1481-fold for MDT-637 and 3.29-fold for aerosolized ribavirin. Maximal peak and trough levels of oral or intravenous ribavirin were significantly lower than their IC50 s. We also measured MDT-637 IC50 s in 3 lab strains and 4 clinical strains. The IC50 s ranged from 0.36 to 3.4 ng/mL. Achievable human MDT-637 concentrations in respiratory secretions exceed the IC50 s by factors from hundreds to thousands of times greater than does ribavirin. Furthermore, MDT-637 has broad in vitro antiviral activity on clinical strains of different RSV genotypes and clades. Together, these data imply that MDT-637 may produce a superior clinical effect compared to ribavirin on natural RSV infections. PMID- 28990343 TI - Efficacy and Safety of a Biodegradable Polymer Cobalt-Chromium Sirolimus-Eluting Stent (EXCEL2) in Treating De Novo Coronary Artery Disease: A Pooled Analysis of the CREDIT II and CREDIT III Trials. DOI: 10.1002/ccd.26887. PMID- 28990344 TI - Treating of aortic valve stenosis in real-life: A multifaceted decision-making challenge. AB - In this issue of CCI, Vejpongsa and coworkers showed that TAVR represented 20.4% of all aortic valve replacements performed in elderly patients from 21 US states in the year 2013. Patients treated with SAVR or TAVR largely overlapped in their baseline characteristics, indicating that both modalities concur in everyday life. One out of six patients was readmitted within 30 days, with no significant differences between the TAVR and SAVR in propensity score analysis. One may ask: since the indications of transcatheter and surgical treatments are interchanged for many cases, and the global results look similar, how to finally select the best therapeutic option for an individual case? Would the results be the same if patient-reported outcomes and experiences, such as pain and analgesic use, time to return to routine activities, or quality of life scores were measured? Combining traditional and patient-reported outcomes, in relation to costs, is the optimal approach to assess value in healthcare. Time has come for investigators to adopt value-based healthcare measures as endpoints in registries and clinical trials. PMID- 28990345 TI - Is adjustment disorder unidimensional or multidimensional? Implications for ICD 11. AB - In preparation for ICD-11, the adjustment disorder (AjD) diagnosis has undergone considerable revisions; however, the latent structure of AjD remains uncertain. It is unclear whether AjD is best represented as a unidimensional or multidimensional construct. This study performed a comprehensive assessment of the latent structure of AjD symptomatology and assessed its concurrent and discriminant validity. Individuals who experienced involuntary job loss (N = 333) completed a self-report measure of AjD symptoms. Seven alternative models of AjD were tested using confirmatory factor analysis. General psychological distress, impairment in social functioning, occupational self-efficacy, and sense of coherence were used as criterion variables for construct validity. In the confirmatory factor analysis, a bifactor solution with one dominant general AjD factor and 5 correlated group factors (preoccupation, failure-to-adapt, avoidance, affective reaction, and impulsivity) provided optimal fit. As expected, the AjD factor showed strong positive associations with general psychological distress and impairments in social functioning and moderately negative associations with occupational self-efficacy and sense of coherence. With regard to unidimensionality or multidimensionality of AjD symptoms, the current results indicate the plausibility of a unidimensional conceptualization. Future research should focus on essential key characteristics and a reduction of symptoms for the AjD definition. PMID- 28990346 TI - Risk factors for resurgery in men with artificial urinary sphincter: Role of urethral strictures. AB - OBJECTIVE: The aims of the present study were to evaluate the outcome of implantation of an artificial urinary sphincter (AUS) in male patients with iatrogenic urinary incontinence and to analyse possible risk factors for resurgery, with particular focus on the effects of posterior urethral strictures (US). METHODS: The outcomes of AUS implantation surgeries performed by 2 surgeons on consecutive patients between January 1999 and 2015 were evaluated retrospectively. Univariate analysis with Cox proportional hazard regression was used to assess correlations between resurgery (explantation or substitution of the urethral cuff) and risk factors. Hazard ratios (HR) associated with AUS survival and 95% confidence intervals (CI) were calculated and Kaplan-Meier were constructed. Patients who underwent resurgery for mechanical failure were excluded from the study. RESULTS: In all, 73 male patients were monitored for a maximum of 190 months (median follow-up duration 36 months). The risk of resurgery was 3.75-fold greater in patients with than without stenosis (HR 3.75; 95% CI 1.47-9.59). In addition, Kaplan-Meier survival curves showed a significantly shorter AUS survival time in patients with than without stenosis treatment. CONCLUSIONS: Prior treatment for US increases the relative risk of AUS failure. Despite not being an absolute contraindication for AUS implantation, we suggest that patients with previous treatment for US are informed of potential risks. PMID- 28990347 TI - October 2017 at a glance: phenotyping heart failure, co-morbidities, use of evidence-based therapy and new treatments. PMID- 28990348 TI - Larvicidal Activity of Essential Oils of Five Apiaceae Taxa and Some of Their Main Constituents Against Culex quinquefasciatus. AB - Apiaceae are aromatic herbs producing essential oils which are used on an industrial scale for various purposes. Notably, Apiaceae essential oils may replace synthetic insecticides keeping most of their efficacy and avoiding environmental pollution and human poisoning. In the present work, we explored the insecticidal potential of the essential oils from five Apiaceae taxa, namely Sison amomum, Echinophora spinosa, Heracleum sphondylium subsp. sphondylium, Heracleum sphondylium subsp. ternatum, and Trachyspemum ammi, as well as their major constituents (sabinene, p-cymene, terpinolene, myristicin, and thymol), against the filariasis vector Culex quinquefasciatus. For the purpose, the essential oils were obtained by hydrodistillation and their composition was achieved by gas chromatography/mass spectrometry (GC/MS). Their acute toxicity on third instar larvae of C. quinquefasciatus was determined. The two most active essential oils were those from T. ammi fruits and E. spinosa roots, showing LC50 below 20 MUl/l and LD90 below 50 MUl/l. These oils were dominated by the monoterpene phenol thymol and the phenylpropanoid myristicin, respectively, which showed the strongest larvicidal activity (LC50 of 15.1 and 16.3 MUl/l, respectively) among the pure compounds tested. These results showed that Apiaceae may be useful as source of larvicidal compounds to be used for the development of cheap, effective and eco-friendly insecticidal formulations. PMID- 28990349 TI - STAMPEDE-ing towards androgen biosynthesis inhibition for treatment of high-risk hormone-naive prostate cancer: changing the LATITUDE. PMID- 28990350 TI - Association of DNMT3b gene variants with sporadic Parkinson's disease in a Chinese Han population. AB - BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder worldwide. Epigenetic modifications, specifically DNA methylation, have been implicated in the development of this disease. Genetic variants of DNA methyltransferase 3b (DNMT3b), one of the most important DNA methyltransferases, were shown to be associated with PD in a Brazilian population. However, it is unclear whether genetic variants of DNMT3b increase the risk of PD in the Chinese Han people. The present study aimed to investigate the association of the DNMT3b variants rs2424913, rs998382 and rs2424932 with PD in a Chinese Han population. METHODS: We studied 487 Chinese Han patients with sporadic PD and 485 healthy age , sex- and ethnicity-matched controls. DNA was extracted from peripheral blood leukocytes and the individual genotypes were determined using the SNaPshot method. RESULTS: We found that the rs2424932 and rs998382 variants were significantly associated with an increased risk of PD compared to the controls [rs2424932: odds ratio (OR) = 1.632, 95% confidence interval (CI) = 1.108-2.406, p = 0.013; rs998382: OR = 1.612, 95% CI = 1.103-2.382, p = 0.014]. Subgroup analysis suggested that female patients carrying the rs2424932 or rs998382 variants were more likely to develop PD than female controls (rs2424932: OR = 3.863, 95% CI = 2.004-7.445, p < 0.001; rs998382: OR = 3.679, 95% CI = 1.943 6.964, p < 0.001). Haplotype analysis indicated that the three variants comprised one block and that the Trs2424913 -Crs998382 -A rs2424932 haplotype was correlated with an increased risk of PD (p = 0.0046), especially for Chinese Han females (p < 0.0001). CONCLUSIONS: The results of the present study strongly suggest that DNMT3b variants are associated with PD in the Chinese Han people, especially females. PMID- 28990351 TI - Human capabilities in advanced dementia: Nussbaum's approach. AB - AIMS AND OBJECTIVES: To explore how Martha Nussbaum's approach to human capabilities can apply to dignity in the lives of people with advanced dementia living in nursing homes. BACKGROUND: Challenges experienced when supporting people with advanced dementia who express problematic behaviours include understanding their needs and ensuring a dignified life for them. DESIGN AND METHODS: Data were gathered using an ethnographic approach based on participatory observation. Nussbaum's capability approach was then used as a framework for the analysis. Four women diagnosed with advanced dementia who also expressed problematic behaviours were recruited from a nursing home in Northern Sweden. The data collection was performed during 2015. FINDINGS: Individuals with advanced dementia had difficulties in participating in the planning of their lives and achieving the human capability of practical reasoning. They were also at risk of being placed outside the social group, thus hindering them from attaining the human capability of affiliation. A dignified life for individuals with advanced dementia requires nursing staff to be present and to provide adapted support to ensure that the individual can actually pursue human capabilities. CONCLUSION: Creating opportunities for the human capabilities of practical reasoning and affiliation is essential as they permeate all other human capabilities. For these individuals, it was crucial not only to create opportunities for human capabilities but also to attend to their expressions and needs and to guide and steer them towards a dignified life. IMPLICATIONS FOR PRACTICE: The normative structure of the capability approach described by Nussbaum can ensure that nursing staffs move beyond fulfilling patients' basic needs to consider other capabilities vital for a dignified life. PMID- 28990352 TI - Flexible Zirconium MOFs as Bromine-Nanocontainers for Bromination Reactions under Ambient Conditions. AB - A series of flexible MOFs (PCN-605, PCN-606, and PCN-700) are synthesized and applied to reversible bromine encapsulation and release. The chemical stability of these Zr-MOFs ensures the framework's integrity during the bromine adsorption, while the framework's flexibility allows for structural adaptation upon bromine uptake to afford stronger host-guest interactions and therefore higher bromine adsorption capacities. The flexible MOFs act as bromine-nanocontainers which elongate the storage time of volatile halides under ambient conditions. Furthermore, the bromine pre-adsorbed flexible MOFs can be used as generic bromine sources for bromination reactions giving improved yields and selectivities under ambient conditions when compared with liquid bromine. PMID- 28990353 TI - Professor Thue W. Schwartz is the BCPT Nordic Prize Winner 2017 in Basic & Clinical Pharmacology & Toxicology. PMID- 28990354 TI - Influence of atrial contraction dynamics on cardiac function. AB - In recent years, there has been a move from monoventricular or biventricular models of the heart, to more complex models that incorporate the electromechanical function in all 4 chambers. However, the biophysical foundation is still underdeveloped, with most work in atrial cellular models having focused on electrophysiological properties. Here, we present a biophysical model of human atrial contraction at body temperature and use it to study the effects of atrial contraction on whole organ function and a study of the effects of remodelling due to atrial fibrillation on atrial and ventricular function. PMID- 28990355 TI - Sickness Status and Neural Tube Defects: A Case-Control Study in a North Indian Population. AB - BACKGROUND: The prevalence of neural tube defects (NTDs) in India is high in comparison to other regions in the world, with the Northern part reporting the highest prevalence. METHODS: To explore the risk factors for NTDs, a case-control study was carried out in Delhi from January 2008 to June 2011. Using multivariate logistic regression model analysis, 308 cases were compared with 580 controls and adjusted odds ratio (AOR) was calculated using SPSS version 17. RESULTS: Maternal factors that were significantly associated with increased risk of NTDs were inter pregnancy interval (AOR = 3.175; 95% confidence interval [CI], 2.007-5.024), hyperthermia during the first trimester (AOR = 2.07; 95% CI, 1.131-3.788), maturation ill pregnancy (AOR = 1.956; 95% CI, 1.385-2.763), chronic illness (AOR = 1.648; 95% CI, 1.103-2.462), and use of antibiotics (AOR = 5.589; 95% CI, 1.789 17.455). Differences in the risk were also found between upper and lower NTD. It was observed that all of the former five variables, except for chronic illness, were associated with risk for upper NTDs (AOR = 1.532; 95% CI, 0.916-2.563). In contrast, hyperthermia before conception (and not during the first trimester) was found to be additionally associated with risk for lower NTDs (AOR = 2.782; 95% CI, 1.302-5.944). CONCLUSION: These findings highlight heterogeneity in the etiology of upper and lower NTDs. The study also highlights the risk factors that should be considered in combating the risk of NTDs. Birth Defects Research 109:1393-1399, 2017.(c) 2017 Wiley Periodicals, Inc. PMID- 28990356 TI - Thalidomide Embryopathy as Possible Cause of Anterior Sacral Meningocele: A Case Report. AB - A 54-year-old male presented with a sudden burning sensation during urination and left flank pain. Apart from having congenital facial palsy and malformation of the inner right ear that was linked to thalidomide embryopathy, the patient has always been in good health. Urine examination showed the presence of a urinary tract infection. An abdominal ultrasound revealed a large cyst in the lower abdomen, which on MRI corresponded to a large anterior sacral meningocele (ASM) with sacral agenesis at S1/S2. After antibiotic treatment and the spontaneous passage of a kidney stone, the symptoms resolved. This suggests that the patient's acute symptoms were caused by the urolithiasis and not the ASM. Thalidomide is teratogenic between days 17 and 30 after conception. The neural tube closes between days 20 and 36, therefore, thalidomide embryopathy was the possible cause of ASM in this patient. Birth Defects Research 109:1390-1392, 2017.(c) 2017 Wiley Periodicals, Inc. PMID- 28990357 TI - Procedural learning across the lifespan: A systematic review with implications for atypical development. AB - This systematic review aimed to investigate procedural learning across the lifespan in typical and atypical development. Procedural learning is essential for the development of everyday skills, including language and communication skills. Although procedural learning efficiency has been extensively studied, there is no consensus yet on potential procedural learning changes during development and ageing. Currently, three conflicting models regarding this trajectory exist: (1) a model of age invariance; (2a) a model with a peak in young adulthood; and (2b) a model with a plateau in childhood followed by a decline. The aims of this study were (1) to investigate this debate on procedural learning across the lifespan by systematically reviewing evidence for each model from studies using the serial reaction time task; and (2) to review procedural learning in autism spectrum disorder (ASD) and specific language impairment (SLI), two developmental disorders characterized by deficits in communication skills, in the light of these models. Our findings on typical development strongly support a model of age-related changes (Model 2a or 2b) and show that mixed findings regarding the developmental trajectory during childhood can be explained by methodological differences across studies. Applying these conclusions to systematic reviews of studies of ASD and SLI makes it clear that there is a strong need for the inclusion of multiple age groups in these clinical studies to model procedural learning in atypical development. Clinical implications of the findings are discussed. Future research should focus on the role of declarative learning in both typical and atypical development. PMID- 28990358 TI - Long-term safety of intravenous cardiovascular agents in acute heart failure: results from the European Society of Cardiology Heart Failure Long-Term Registry. AB - AIMS: The aim of this study was to assess long-term safety of intravenous cardiovascular agents-vasodilators, inotropes and/or vasopressors-in acute heart failure (AHF). METHODS AND RESULTS: The European Society of Cardiology Heart Failure Long-Term (ESC-HF-LT) registry was a prospective, observational registry conducted in 21 countries. Patients with unscheduled hospitalizations for AHF (n = 6926) were included: 1304 (18.8%) patients received a combination of intravenous (i.v.) vasodilators and diuretics, 833 (12%) patients received i.v. inotropes and/or vasopressors. Primary endpoint was long-term all-cause mortality. Main secondary endpoints were in-hospital and post-discharge mortality. Adjusted hazard ratio (HR) showed no association between the use of i.v. vasodilator and diuretic and long-term mortality [HR 0.784, 95% confidence interval (CI) 0.596-1.032] nor in-hospital mortality (HR 1.049, 95% CI 0.592 1.857) in the matched cohort (n = 976 paired patients). By contrast, adjusted HR demonstrated a detrimental association between the use of i.v. inotrope and/or vasopressor and long-term all-cause mortality (HR 1.434, 95% CI 1.128-1.823), as well as in-hospital mortality (HR 1.873, 95% CI 1.151-3.048) in the matched cohort (n = 606 paired patients). No association was found between the use of i.v. inotropes and/or vasopressors and long-term mortality in patients discharged alive (HR 1.078, 95% CI 0.769-1.512). A detrimental association with inotropes and/or vasopressors was seen in all geographic regions and, among catecholamines, dopamine was associated with the highest risk of death (HR 1.628, 95% CI 1.031 2.572 vs. no inotropes). CONCLUSIONS: Vasodilators did not demonstrate any association with long-term clinical outcomes, while inotropes and/or vasopressors were associated with increased risk of all-cause death, mostly related to excess of in-hospital mortality in AHF. PMID- 28990359 TI - Ancestry-specific and sex-specific risk alleles identified in a genome-wide gene by-alcohol dependence interaction study of risky sexual behaviors. AB - We previously mapped loci for the genome-wide association studies (GWAS) and genome-wide gene-by-alcohol dependence interaction (GW-GxAD) analyses of risky sexual behaviors (RSB). This study extends those findings by analyzing the ancestry- and sex-specific AD-stratified effects on RSB. We examined the concordance of findings for the AD-stratified GWAS and the GW-GxAD analysis of RSB, with concordance defined as genome-wide significance in one analysis and at least nominal significance in the second analysis. A total of 2,173 African American (AA) and 1,751 European-American (EA) subjects were investigated. Information regarding RSB (lifetime experiences of unprotected sex and multiple sexual partners) and DSM-IV diagnosis of lifetime AD were derived from the Semi Structured Assessment for Drug Dependence and Alcoholism (SSADDA). In our ancestry- and sex-specific analyses, we identified four independent genome-wide significant (GWS) loci (p < 5*10-8 ) and one suggestive locus (p < 6*10-8 ). In men, we observed a GWS signal in FAM162A (rs2002594, p = 4.96*10-8 ). In women, there was a suggestive locus in PLGRKT (rs3824435, p = 5.52*10-8 ). In AAs, there was a GWS signal in GRK5 (rs1316543, p = 1.25*10-9 ). In AA men, we observed an intergenic GWS signal (rs12898370, p = 4.49*10-8 ) near LINGO1. In EA men, there was a GWS signal in CCSER1 (rs62313897; p = 7.93*10-10 ). The loci identified in this GWAS implicate molecular mechanisms related to psychiatric illness and personality features, suggesting that the interplay between AD and RSB is mediated by alleles associated with behavioral traits. PMID- 28990360 TI - Effects of Genetic Variants on Carboxylesterase 1 Gene Expression, and Clopidogrel Pharmacokinetics and Antiplatelet Effects. AB - Several single nucleotide variations (SNVs) affect carboxylesterase 1 (CES1) activity, but the effects of genetic variants on CES1 gene expression have not been systematically investigated. Therefore, our aim was to investigate effects of genetic variants on CES1 gene expression in two independent whole blood sample cohorts of 192 (discovery) and 88 (replication) healthy volunteers and in a liver sample cohort of 177 patients. Furthermore, we investigated possible effects of the found variants on clopidogrel pharmacokinetics (n = 106) and pharmacodynamics (n = 46) in healthy volunteers, who had ingested a single 300 mg or 600 mg dose of clopidogrel. Using massively parallel sequencing, we discovered two CES1 SNVs, rs12443580 and rs8192935, to be strongly and independently associated with a 39% (p = 4.0 * 10-13 ) and 31% (p = 2.5 * 10-8 ) reduction in CES1 whole blood expression per copy of the minor allele. These findings were replicated in the replication cohort. However, these SNVs did not affect CES1 liver expression, or clopidogrel pharmacokinetics or pharmacodynamics. Conversely, the CES1 c.428G>A missense SNV (rs71647871) impaired the hydrolysis of clopidogrel, increased exposure to clopidogrel active metabolite and enhanced its antiplatelet effects. In conclusion, the rs12443580 and rs8192935 variants reduce CES1 expression in whole blood but not in the liver. These tissue-specific effects may result in substrate-dependent effects of the two SNVs on CES1-mediated drug metabolism. PMID- 28990362 TI - An explorative study on the validity of various definitions of a 2.2 degrees C temperature threshold as warning signal for impending diabetic foot ulceration. AB - Home monitoring of skin temperature is effective to prevent diabetic foot ulceration. We explored the validity of various definitions for the >2.2 degrees C left-to-right threshold used as a warning signal for impending ulceration. Twenty patients with diabetes and peripheral neuropathy monitored their skin temperature with an infrared thermometer at the plantar hallux, metatarsal heads, midfoot and heel four times a day for 6 consecutive days. Environmental temperature and walking activity were monitored and associated with foot temperature. The average temperature difference between feet was 0.65 degrees C. At single locations, a left-to-right temperature difference of >2.2 degrees C was found 245 times (8.5% of measurements). Confirmation of these above-threshold readings on the following day was found seven times (0.3%). Corrected for individual left-to-right mean foot temperature differences, this reduced to four (0.2%). No ulcers developed in the week after monitoring. Left-to-right foot temperature differences were not significantly correlated with walking activity, environmental temperature or time of day. The >2.2 degrees C left-to-right foot temperature threshold for impending ulceration is not valid as single measurement, but validity improves to acceptable levels when an above-threshold temperature difference is confirmed the following day and further improves with individual correction. The threshold is independent of time of day, environmental temperature and walking activity. PMID- 28990363 TI - Light-Harvesting Organic Nanocrystals Capable of Photon Upconversion. AB - Harvesting and converting low energy photons into higher ones through upconversion have great potential in solar energy conversion. A light-harvesting nanocrystal assembled from 9,10-distyrylanthracene and palladium(II) meso tetraphenyltetrabenzoporphyrin as the acceptor and the sensitizer, respectively effects red-to-green upconversion under incoherent excitation of low power density. An upconversion quantum yield of 0.29+/-0.02 % is obtained upon excitation with 640 nm laser of 120 mW cm-2 . The well-organized packing of acceptor molecules with aggregation-induced emission in the nanocrystals dramatically reduces the nonradiative decay of the excited acceptor, benefits the triplet-triplet annihilation (TTA) upconversion and guides the consequent upconverted emission. This work provides a straightforward strategy to develop light-harvesting nanocrystals based on TTA upconversion, which is attractive for energy conversion and photonic applications. PMID- 28990361 TI - Characterization of garlic endophytes isolated from the black garlic processing. AB - The objectives of this study were to isolate and identify garlic endophytes, and explore the characteristics of dominant strains. Garlic endophytes were studied through phenotypical characterization and comparative sequence analysis of 16S rDNA based on culture-dependent approaches. Representative strains inferred from 16S rDNA sequencing were selected for further identification by gyrA and rpoB gene loci and phylogenetic analysis based on concateneted house-keeping sequences. Seven kinds of Bacillus were found from garlic and black garlic, respectively. Further studies demonstrated that the total bacteria and endophytes showed a sharp decrease firstly, followed by a rapid rise, then maintained at a certain level, and finally slowed down during the black garlic processing. B. subtilis, B. methylotrophicus, and B. amyloliquefaciens were the dominant strains. The selected strains were capable of fermenting glucose, lactose, sucrose, and garlic polysaccharide to produce acid but no gas, with a strong ability of heat resistance. The results indicated that there were a certain number of garlic endophytes during the black garlic processing, and Bacillus was the dominant strains under the conventional culture-dependent methods. This report provided useful information for the presence and type of garlic endophytes during the black garlic processing, which were of great significance to study the formation mechanism and quality improvement of black garlic in the future, as well as the security of garlic powder. PMID- 28990364 TI - Synthesis, Functionalization, and Design of Magnetic Nanoparticles for Theranostic Applications. AB - In order to translate nanotechnology into medical practice, magnetic nanoparticles (MNPs) have been presented as a class of non-invasive nanomaterials for numerous biomedical applications. In particular, MNPs have opened a door for simultaneous diagnosis and brisk treatment of diseases in the form of theranostic agents. This review highlights the recent advances in preparation and utilization of MNPs from the synthesis and functionalization steps to the final design consideration in evading the body immune system for therapeutic and diagnostic applications with addressing the most recent examples of the literature in each section. This study provides a conceptual framework of a wide range of synthetic routes classified mainly as wet chemistry, state-of-the-art microfluidic reactors, and biogenic routes, along with the most popular coating materials to stabilize resultant MNPs. Additionally, key aspects of prolonging the half-life of MNPs via overcoming the sequential biological barriers are covered through unraveling the biophysical interactions at the bio-nano interface and giving a set of criteria to efficiently modulate MNPs' physicochemical properties. Furthermore, concepts of passive and active targeting for successful cell internalization, by respectively exploiting the unique properties of cancers and novel targeting ligands are described in detail. Finally, this study extensively covers the recent developments in magnetic drug targeting and hyperthermia as therapeutic applications of MNPs. In addition, multi-modal imaging via fusion of magnetic resonance imaging, and also innovative magnetic particle imaging with other imaging techniques for early diagnosis of diseases are extensively provided. PMID- 28990367 TI - Continuing Professional Development. PMID- 28990368 TI - Future proofing radiologists. PMID- 28990369 TI - Frederick Schubert BSc, MBBS, FRACR, FRCR, BA, DDU (1926-2017). PMID- 28990365 TI - Endocannabinoid-related compounds in gastrointestinal diseases. AB - The endocannabinoid system (ECS) is an endogenous signalling pathway involved in the control of several gastrointestinal (GI) functions at both peripheral and central levels. In recent years, it has become apparent that the ECS is pivotal in the regulation of GI motility, secretion and sensitivity, but endocannabinoids (ECs) are also involved in the regulation of intestinal inflammation and mucosal barrier permeability, suggesting their role in the pathophysiology of both functional and organic GI disorders. Genetic studies in patients with irritable bowel syndrome (IBS) or inflammatory bowel disease have indeed shown significant associations with polymorphisms or mutation in genes encoding for cannabinoid receptor or enzyme responsible for their catabolism, respectively. Furthermore, ongoing clinical trials are testing EC agonists/antagonists in the achievement of symptomatic relief from a number of GI symptoms. Despite this evidence, there is a lack of supportive RCTs and relevant data in human beings, and hence, the possible therapeutic application of these compounds is raising ethical, political and economic concerns. More recently, the identification of several EC-like compounds able to modulate ECS function without the typical central side effects of cannabino-mimetics has paved the way for emerging peripherally acting drugs. This review summarizes the possible mechanisms linking the ECS to GI disorders and describes the most recent advances in the manipulation of the ECS in the treatment of GI diseases. PMID- 28990370 TI - Importance of quality in radiation oncology. PMID- 28990371 TI - Exploring animal rabies endemicity to inform control programmes in Punjab, India. AB - Previous studies estimate that one-third of the annual global burden of rabies (~20,000 cases) occurs in India. Elimination of canine rabies is essential to reduce this burden. Surveillance of animal cases can assess both the risk to humans and the efficacy of control strategies. The objective of this study was to describe the spatial and temporal occurrence of reported confirmed cases of rabies in animals in Punjab, India, from 2004 to 2014. We analysed passive surveillance data on 556 samples submitted from 2004 to 2014 to GADVASU, Ludhiana, Punjab, India. Regression and time series analyses were conducted to understand seasonal and long-term variation of cases and identify cross correlation of monthly cases between species. Spatio-temporal analyses assessed spatial autocorrelation of date of reporting, mean geographic centres of disease occurrence and clustering of cases using Kulldorff's space-time permutation statistic. The annual number of submissions and proportion of confirmed cases were consistent throughout 2004-2014. Most submissions (320; 57.6%) were confirmed rabies cases, including dogs (40.6%), buffalo (29.7%) and cattle (23.1%). Regression analysis of monthly cases in dogs showed seasonal variation with significant increases in cases in March and August. Monthly case numbers in buffalo decreased over time. Long-term temporal trend was not detected in dog and cattle cases. Time-series models identified significant cross-correlation between dog and buffalo cases, suggesting that buffalo cases were spillover events from dogs. Significant spatio-temporal variation or clusters of cases were not detected. These results indicate that rabies cases in animals-and therefore, the potential for exposure to humans-were temporally and spatially stable during 2004 2014 in Punjab, India. The endemic nature of rabies transmission in this region demands a coordinated, sustained control programme. This study provides baseline information for assessing the efficacy of rabies control measures and developing seasonally targeted dog vaccination and rabies awareness strategies. PMID- 28990372 TI - ATP Binding Cassette Sub-family Member 2 (ABCG2) and Xenobiotic Exposure During Early Mouse Embryonic Stem Cell Differentiation. AB - BACKGROUND: ATP binding cassette sub-family member 2 (ABCG2) is a well-defined efflux transporter found in a variety of tissues. The role of ABCG2 during early embryonic development, however, is not established. Previous work which compared data from the ToxCast screening program with that from in-house studies suggested an association exists between exposure to xenobiotics that regulate Abcg2 transcription and differentiation of mouse embryonic stem cells (mESC), a relationship potentially related to redox homeostasis. METHODS: mESC were grown for up to 9 days. Pharmacological inhibitors were used to assess transporter function with and without xenobiotic exposure. Proliferation and differentiation were evaluated using RedDot1 and quantiative reverse transcriptase-polymerase chain reaction, respectively. ABCG2 activity was assessed using a Pheophorbide a based fluorescent assay. Protein expression was measured by capillary-based immunoassay. RESULTS: ABCG2 activity increased in differentiating mESC. Treatment with K0143, an inhibitor of ABCG2, had no effect on proliferation or differentiation. As expected, mitoxantrone and topotecan, two chemotherapeutics, displayed increased toxicity in the presence of K0143. Exposure to K0143 in combination with chemicals predicted by ToxCast to regulate ABCG2 expression did not alter xenobiotic-induced toxicity. Moreover, inhibition of ABCG2 did not shift the toxicity of either tert-Butyl hydroperoxide or paraquat, two oxidative stressors. CONCLUSION: As previously reported, ABCG2 serves a protective role in mESC. The role of ABCG2 in regulating redox status, however, was unclear. The hypothesis that ABCG2 plays a fundamental role during mESC differentiation or that regulation of the receptor by xenobiotics may be associated with altered mESC differentiation could not be supported. Birth Defects Research, 110:35-47, 2018. Published 2017. This article is a U.S. Government work and is in the public domain in the USA. PMID- 28990373 TI - Sigma-1 receptor agonist increases axon outgrowth of hippocampal neurons via voltage-gated calcium ions channels. AB - INTRODUCTION: Sigma-1 receptors (Sig-1Rs) are unique endoplasmic reticulum proteins that have been implicated in both neurodegenerative and ischemic diseases, such as Alzheimer's disease and stroke. Accumulating evidence has suggested that Sig-1R plays a role in neuroprotection and axon outgrowth. The underlying mechanisms of Sig-1R-mediated neuroprotection have been well elucidated. However, the mechanisms underlying the effects of Sig-1R on axon outgrowth are not fully understood. METHODS: To clarify this issue, we utilized immunofluorescence to compare the axon lengths of cultured naive hippocampal neurons before and after the application of the Sig-1R agonist, SA4503. Then, electrophysiology and immunofluorescence were used to examine voltage-gated calcium ion channel (VGCCs) currents in the cell membranes and growth cones. RESULTS: We found that Sig-1R activation dramatically enhanced the axonal length of the naive hippocampal neurons. Application of the Sig-1R antagonist NE100 and gene knockdown techniques both demonstrated the effects of Sig-1R. The growth promoting effect of SA4503 was accompanied by the inhibition of voltage-gated Ca2+ influx and was recapitulated by incubating the neurons with the L-type, N type, and P/Q-type VGCC blockers, nimodipine, MVIIA and omega-agatoxin IVA, respectively. This effect was unrelated to glial cells. The application of SA4503 transformed the growth cone morphologies from complicated to simple, which favored axon outgrowth. CONCLUSION: Sig-1R activation can enhance axon outgrowth and may have a substantial influence on neurogenesis and neurodegenerative diseases. PMID- 28990374 TI - Transcriptome sequencing and annotation of the halophytic microalga Dunaliella salina. AB - The unicellular green alga Dunaliella salina is well adapted to salt stress and contains compounds (including beta-carotene and vitamins) with potential commercial value. A large transcriptome database of D. salina during the adjustment, exponential and stationary growth phases was generated using a high throughput sequencing platform. We characterized the metabolic processes in D. salina with a focus on valuable metabolites, with the aim of manipulating D. salina to achieve greater economic value in large-scale production through a bioengineering strategy. Gene expression profiles under salt stress verified using quantitative polymerase chain reaction (qPCR) implied that salt can regulate the expression of key genes. This study generated a substantial fraction of D. salina transcriptional sequences for the entire growth cycle, providing a basis for the discovery of novel genes. This first full-scale transcriptome study of D. salina establishes a foundation for further comparative genomic studies. PMID- 28990375 TI - Nominal effective immunoreaction volume of magnetic beads at single bead level. AB - Immunomagnetic bead (IMB)-based enzyme-linked immunosorbent assay (ELISA) has been the tool frequently used for protein detection in research and clinical laboratories. For most ELISA reactions the recommended dosage of IMBs is usually according to their weight (mg) or mass fraction (w/v) instead of the bead number. Consequently, the processes occurring in the immediate vicinity of the IMBs have always been ignored by researchers and they cannot be revealed in detail during the ELISA reaction. In this paper, we established the relationship between number of IMBs and colorimetric results, and further proposed a new concept of "nominal effective immunoreaction volume (NEIV)" to characterize a single IMB during ELISA reaction. Results showed that the NEIV of a single IMB has a constant value, which is unrelated to the amount of beads and the concentration of antigen. Optimal results of the colorimetric ELISA are achieved when the incubation volume meets each IMB's NEIV and is no longer enhanced by increasing the incubation volume. Thus, the reliable and relatively precise number of IMBs for ELISA detection during practical application could be determined. Most importantly, a study using IMB's NEIV would lay the foundation for a kinetics analysis of IMBs and antigens for future study. PMID- 28990376 TI - Phenolic compounds participating in mulberry juice sediment formation during storage. AB - The stability of clarified juice is of great importance in the beverage industry and to consumers. Phenolic compounds are considered to be one of the main factors responsible for sediment formation. The aim of this study is to investigate the changes in the phenolic content in clarified mulberry juice during storage. Hence, separation, identification, quantification, and analysis of the changes in the contents of phenolic compounds, both free and bound forms, in the supernatant and sediments of mulberry juice, were carried out using high performance liquid chromatographic system, equipped with a photo-diode array detector (HPLC-PDA) and HPLC coupled with quadrupole-time of flight mass spectrometric (HPLC-QTOF-MS/MS) techniques. There was an increase in the amount of sediment formed over the period of study. Total phenolic content of supernatant, as well as free phenolic content in the extracts of the precipitate decreased, whereas the bound phenolic content in the sediment increased. Quantitative estimation of individual phenolic compounds indicated high degradation of free anthocyanins in the supernatant and sediment from 938.60 to 2.30 mg/L and 235.60 to 1.74 mg/g, respectively. A decrease in flavonoids in the supernatant was also observed, whereas the contents of bound forms of gallic acid, protocatechuic acid, caffeic acid, and rutin in the sediment increased. Anthocyanins were the most abundant form of phenolics in the sediment, and accounted for 67.2% of total phenolics after 8 weeks of storage. These results revealed that phenolic compounds, particularly anthocyanins, were involved in the formation of sediments in mulberry juice during storage. PMID- 28990377 TI - Stability of beta-carotene microcapsules with Maillard reaction products derived from whey protein isolate and galactose as coating materials. AB - The stability of beta-carotene microcapsules using Maillard reaction products (MRPs) derived from whey protein isolate (WPI) and galactose as coating materials, was studied under the varying environmental conditions of temperature, pH, air, incandescent light, and ultraviolet (UV) light. Scanning electron microscopy showed that microcapsules prepared by WPI-galactose MRPs displayed a smooth and less concave-convex surface and that the particle size (D50) of the microcapsules made with WPI-galactose MRPs was smaller than those made with WPI galactose mixture. The storage stability of beta-carotene microencapsulated in WPI-galactose MRPs was remarkably better than that of beta-carotene microencapsulated in the WPI-galactose mixture and that of beta-carotene crystal, in respect of temperature, pH, air, incandescent light, and UV light measurements. When the storage temperature was increased from 5 to 105 degrees C, the retention rate of beta-carotene microcapsules significantly decreased (P<0.05). When pH values were increased from 1 to 12, the beta-carotene retention rate of the microcapsules significantly increased and afterward decreased. Compared with the retention rate of beta-carotene microencapsulated in a WPI galactose mixture, the retention rate of beta-carotene microencapsulated in WPI galactose MRPs was at a maximum between pH 8 and 9. Under the actions of air, incandescent light, and UV light, the retention rates of beta-carotene microcapsules in WPI-galactose MRPs and WPI-galactose mixture, as well as in beta carotene crystal, decreased significantly as the storage time increased (P<0.05). Therefore, the use of WPI-galactose MRPs as coating materials can aid in improving the storage stability of beta-carotene microcapsules. PMID- 28990379 TI - Effects of neutral phytase on growth performance and phosphorus utilization in crucian carp (Carassius auratus). AB - A feeding trial was conducted for nine weeks to investigate the effects of partially replacing Ca(H2PO4)2 with neutral phytase on the growth performance, phosphorus utilization, nutrient digestibility, serum biochemical parameters, bone and carcass mineral composition, and digestive-enzyme-specific activity in crucian carp (Carassius auratus). The diets prepared with 0.8%, 0%, and 1.8% Ca(H2PO4)2 (1%=1 g/100 g) supplements were regarded as the P1E0, negative control (NC), and positive control (PC) groups, respectively; the other three experimental diets were prepared with the addition of 200, 300, and 500 U/kg of neutral phytase, respectively, based on the P1E0 group. Three hundred and eighty four fish ((1.50+/-0.01) g) were randomly distributed in the six treatments with four replicates each. The fish were initially fed with 2%-3% diets of their body weight per day, with feeding twice daily (08:00 and 16:00), under a 12-h light/12 h dark cycle at the temperature of (27.56+/-0.89) degrees C. The results showed that supplemental phytase at different levels in the diet improved the final body weight, average daily gain, feed conversion ratio, phosphorus utilization, and protein efficiency ratio of crucian carp (P<0.05). Phytase supplementation increased the mineral content in serum (P), bone (P, Ca), and carcass (P, Ca, Zn, Na, and Mg) (P<0.05); the trypsin and chymotrypsin activity soared when fed with the phytase-supplemented diets (P<0.05). We may conclude that supplemental dietary neutral phytase improved the growth performance, phosphorus utilization as well as nutrient utilization in crucian carp, and it can be considered an important nutritional replacement for Ca(H2PO4)2. PMID- 28990378 TI - Optimization of low-abundance protein extraction and abundant protein removal from defatted soybean meal. AB - The aim of this study was to optimize the conditions for the extraction of low abundance proteins (LAPs) and the removal of abundant proteins (APs; beta conglycinin and glycinin) from soybean meal. Single factor and orthogonal experiments were designed to determine the effects of four factors (isopropanol concentration, total extraction time, ultrasonic power, and ultrasonic time) on protein concentration in isopropanol extracts. Proteins in the isopropanol supernatant and the cold acetone precipitate of isopropanol were identified by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and matrix assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). The results showed that the optimal conditions were 50% isopropanol, ultrasonic pretreatment for 15 min at 350 W, and a total extraction time of 1 h. Under these conditions, the protein concentration in the isopropanol extracts reached 0.8081 g/L. Many LAPs were detected, including beta-amylase, soybean agglutinin, soybean trypsin inhibitor, fumarylacetoacetase-like, phospholipase D alpha 1-like, oleosin, and even some unknown soybean proteins. The soybean APs (beta-conglycinin and glycinin) were not found. The method may be useful for discovering new soybean proteins and extracting enough LAPs of soybean to allow further studies of their physiological effects on animals without the influence of APs. PMID- 28990380 TI - Effects of split applications of nitrogen fertilizers on the Cd level and nutritional quality of Chinese cabbage. AB - Cadmium (Cd) contamination in soil is an increasingly serious problem. Management of plant nutrients has been proposed as a potentially promising strategy for minimizing Cd accumulation in crops grown in contaminated soil. This study investigated the effects of split applications of nitrogen (N) fertilizers on the Cd concentration in Chinese cabbage (Brassica chinensis L.) plants grown in Cd contaminated soil. Compared with single applications, split applications of ammonium or urea resulted in significantly lower Cd concentrations, and higher biomass production and antioxidant-associated nutritional quality in the edible plant parts. However, when nitrate was used as the N fertilizer, there were no significant differences between the split and single applications for the same parameters. We conclude that a split application could be more beneficial than a single application method when ammonium or urea is used as the N fertilizer for vegetable cultivation in Cd-contaminated soil. PMID- 28990382 TI - Characteristic differences in essential oil composition of six Zanthoxylum bungeanum Maxim. (Rutaceae) cultivars and their biological significance. AB - Great variations have been found in composition and content of the essential oil of Zanthoxylum bungeanum Maxim. (Rutaceae), resulting from various factors such as harvest time, drying and extraction methods (Huang et al., 2006; Shao et al., 2013), solvent and herbal parts used (Zhang, 1996; Cao and Zhang, 2010; Wang et al., 2011). However, in terms of artificial introduction and cultivation, there is little research on the chemical composition of essential oil extracted from Z. bungeanum Maxim. cultivars, which have been introduced from different origins. In this study, the composition and content of essential oil from six cultivars (I VI) have been investigated. They were introduced and cultivated for 11 years in the same cultivation conditions. Cultivars were as followings: Qin'an (I) cultivar originally introduced from Qin'an City in Gansu Province; Dahongpao A (II) from She County in Hebei Province; Dahongpao B (III) from Fuping County; Dahongpao C (IV) from Tongchuan City; Meifengjiao (V) from Feng County; and, Shizitou (VI) from Hancheng City, in Shaanxi Province, China. This research is expected to provide a theoretical basis for further introduction, cultivation, and commercial development of Z. bungeanum Maxim. PMID- 28990381 TI - Enucleation of non-invasive tumors in the proximal pancreas: indications and outcomes compared with standard resections. AB - OBJECTIVE: The aim of this study was to evaluate the safety and efficiency of enucleation (EU) for proximal pancreatic non-invasive neoplasms. METHODS: Patients with solitary non-invasive neoplasms in the proximal pancreas from January 1998 to April 2014 at the Second Affiliated Hospital of Zhejiang University, Hangzhou, China were included. Different operations and outcomes were analyzed. RESULTS: A total of 123 patients were enrolled. Forty patients (32.5%) underwent EU including 18 patients who had tumors close to the main pancreatic duct (MPD). Sixty-one patients (49.6%) had pancreaticoduodenectomy (PD) performed and 22 (17.9%) underwent central pancreatectomy (CP). Pathological outcomes included neuroendocrine tumors, cystic lesions, and solid pseudopapillary tumors. Operation time, intra-operative blood loss, and duration of hospital stay were significantly reduced in the EU group. PD was associated with the greatest complication rate (55.7%), followed by EU (50%) and CP (40.9%), though the pancreatic fistula rate after EU was the highest (50%), especially in patients with tumors larger than 3 cm and tumors close to the MPD. EU had advantages in the preservation of pancreatic parenchyma and endocrine and exocrine function. CONCLUSIONS: EU can be carried out safely and effectively for tumors in the proximal pancreas with improved outcomes compared with standard resections, even if the tumor is larger than 3 cm and close to the MPD. PMID- 28990383 TI - Rational Engineering of Bioinspired Anthocyanidin Fluorophores with Excellent Two Photon Properties for Sensing and Imaging. AB - Fluorescent materials are widely employed in biological analysis owing to their biorthogonal chemistries for imaging and sensing purposes. However, it is always a challenge to design fluorophores with desired photophysical and biological properties, due to their complicated molecular and optical nature. Inspired by anthocyanidin, a class of flower pigments, we designed a new fluorescent molecular framework, AC-Fluor. The new fluorescent materials can be rationally engineered to produce a broad range of fluorescent scaffolds with flexibly tunable emission spectra covering the whole visible light range, from 467 to 707 nm. Furthermore, they exhibit unprecedented environment-insensitive two-photon properties with a substantial cross section as large as 1100 GM in aqueous solution. AC-Fluors demonstrate their biological values through two-photon deep tissue imaging, with penetration depths as much as 300 MUm, while exhibiting minimal cytotoxicity. These features engender a rational engineering strategy for the design and optimization of new fluorescent materials for biological imaging. PMID- 28990384 TI - Selective Binding of Spherical and Linear Anions by Tetraphenyl(thio)urea-Based Dihomooxacalix[4]arene Receptors. AB - Three novel tetra(thio)ureido dihomooxacalix[4]arene anion receptors (phenylurea 4a, phenylthiourea 4b, and tert-butylurea 4c) were synthesized and obtained in the cone conformation in solution, as shown by NMR studies. The X-ray crystal structure of 4c is reported. The host-guest properties of these receptors toward several anions were investigated by 1H NMR titrations. Phenylurea 4a displayed a very efficient binding toward the spherical F- and Cl- anions, and the linear CN- (log Kass = 3.46, 3.50, and 4.02, respectively). In comparison to related bidentate phenylurea dihomooxacalix[4]arenes, tetraphenylurea 4a is more preorganized and the higher number of hydrogen bond donor sites provides a remarkable enhancement of its binding efficiency. PMID- 28990385 TI - Thin Coating of Microporous Organic Network Makes a Big Difference: Sustainability Issue of Ni Electrodes on the PET Textile for Flexible Lithium-Ion Batteries. AB - Poly(ethylene terephthalate) fibers (PET-Fs) were coated with microporous organic networks (MONs) by the Sonogashira coupling of tetra(4-ethynylphenyl)methane with 1,4-diiodobenzene. Ni was deposited on the PET-F@MON via electroless deposition. Interestingly, although Ni on the PET-F showed a sharp decrease in conductivity in repeated bending tests, the PET-F@MON@Ni showed excellent retention of conductivity. We suggest that thin MON layers play roles of an efficient binder for Ni attachment to fibers and a structural buffer for the relaxation of bending strain. The positive effect of MON was supported by scanning electron microscopy studies of the PET-F@Ni or PET-F@MON@Ni retrieved after 2000 bending numbers. Although Ni on the PET-F showed severe detachment after bending tests, PET F@MON@Ni retained the original morphologies. The pouch cells of lithium-ion batteries fabricated using PET-F@MON@Ni as the current collectors showed excellent performance against bending. PMID- 28990386 TI - An Adaptable Phospholipid Membrane Mimetic System for Solution NMR Studies of Membrane Proteins. AB - Based on the saposin-A (SapA) scaffold protein, we demonstrate the suitability of a size-adaptable phospholipid membrane-mimetic system for solution NMR studies of membrane proteins (MPs) under close-to-native conditions. The Salipro nanoparticle size can be tuned over a wide pH range by adjusting the saposin-to lipid stoichiometry, enabling maintenance of sufficiently high amounts of phospholipid in the Salipro nanoparticle to mimic a realistic membrane environment while controlling the overall size to enable solution NMR for a range of MPs. Three representative MPs, including one G-protein-coupled receptor, were successfully incorporated into SapA-dimyristoylphosphatidylcholine nanoparticles and studied by solution NMR spectroscopy. PMID- 28990387 TI - Mechanistic Insight into Caffeine-Oxalic Cocrystal Dissociation in Formulations: Role of Excipients. AB - Caffeine-oxalic acid cocrystal, widely reported to be stable under high humidity, dissociated in the presence of numerous pharmaceutical excipients. In cocrystal excipient binary systems, the water mediated dissociation reaction occurred under pharmaceutically relevant storage conditions. Powder X-ray diffractometry was used to identify the dissociated products obtained as a consequence of coformer excipient interaction. The proposed cocrystal dissociation mechanism involved water sorption, dissolution of cocrystal and excipient in the sorbed water, proton transfer from oxalic acid to the excipient, and formation of metal salts and caffeine hydrate. In compressed tablets with magnesium stearate, the cocrystal dissociation was readily discerned from the appearance of peaks attributable to caffeine hydrate and stearic acid. Neutral excipients provide an avenue to circumvent the risk of water mediated cocrystal dissociation. PMID- 28990388 TI - Carbon-Encapsulated Sn@N-Doped Carbon Nanotubes as Anode Materials for Application in SIBs. AB - Carbon-encapsulated Sn@N-doped carbon tubes with submicron diameters were obtained via the simple reduction of C@SnO2@N-doped carbon composites that were fabricated by a hydrothermal approach. Sn nanoparticles encapsulated in carbon layers were distributed uniformly on the surfaces of the N-doped carbon nanotubes. The electrochemical performances of the composites were systematically investigated as anode materials in sodium-ion batteries (SIBs). The composite electrode could attain a good reversible capacity of 398.4 mAh g-1 when discharging at 100 mA g-1, with capacity retention of 67.3% and very high Coulombic efficiency of 99.7% over 150 cycles. This good cycling performance, when compared to only 17.5 mAh g-1 delivered by bare Sn particles prepared via the same method without the presence of N-doped carbon, could be mainly ascribed to the uniform distribution of the precursor SnO2 on the substrate of N-doped carbon tubes with three-dimensional structure, which provides more reaction sites to reduce the diffusion distance of Na+, further facilitating Na+-ion diffusion and relieves the huge volume expansion during charging/discharging. These outcomes imply that such a Sn/C composite would provide more options as an anode candidate for SIBs. PMID- 28990390 TI - Henry's Constants of Persistent Organic Pollutants by a Group-Contribution Method Based on Scaled-Particle Theory. AB - A group-contribution method based on scaled-particle theory was developed to predict Henry's constants for six families of persistent organic pollutants: polychlorinated benzenes, polychlorinated biphenyls, polychlorinated dibenzodioxins, polychlorinated dibenzofurans, polychlorinated naphthalenes, and polybrominated diphenyl ethers. The group-contribution model uses limited experimental data to obtain group-interaction parameters for an easy-to-use method to predict Henry's constants for systems where reliable experimental data are scarce. By using group-interaction parameters obtained from data reduction, scaled-particle theory gives the partial molar Gibbs energy of dissolution, Deltag2, allowing calculation of Henry's constant, H2, for more than 700 organic pollutants. The average deviation between predicted values of log H2 and experiment is 4%. Application of an approximate van't Hoff equation gives the temperature dependence of Henry's constants for polychlorinated biphenyls, polychlorinated naphthalenes, and polybrominated diphenyl ethers in the environmentally relevant range 0-40 degrees C. PMID- 28990389 TI - Stimulus-Responsive Plasmonic Chiral Signals of Gold Nanorods Organized on DNA Origami. AB - In response to environmental variations, living cells need to arrange the conformational changes of macromolecules to achieve the specific biofunctions. Inspired by natural molecular machines, artificial macromolecular assemblies with controllable nanostructures and environmentally responsive functions can be designed. By assembling macromolecular nanostructures with noble metal nanoparticles, environmental information could be significantly amplified and modulated. However, manufacturing dynamic plasmonic nanostructures that are efficiently responsive to different stimuli is still a challenging task. Here we demonstrate a stimulus-responsive plasmonic nanosystem based on DNA origami organized gold nanorods (GNRs). L-shaped GNR dimers were assembled on rhombus shaped DNA origami templates. The geometry and chiral signals of the GNR nanoarchitectures respond to multiple stimuli, including glutathione reduction, restriction enzyme action, pH change, or photoirradiation. While the glutathione reduction or restriction enzyme caused irreversible changes in the plasmonic circular dichroism (CD) signals, both pH and light irradiation triggered reversible changes in the plasmonic CD. Our system transduces external stimuli into conformational changes and circular dichroism responses in near-infrared (NIR) wavelengths. By this approach, programmable optical reporters for essential biological signals can be fabricated. PMID- 28990391 TI - Fluorinated, Sulfur-Rich, Covalent Triazine Frameworks for Enhanced Confinement of Polysulfides in Lithium-Sulfur Batteries. AB - Lithium-sulfur battery represents a promising class of energy storage technology owing to its high theoretical energy density and low cost. However, the insulating nature, shuttling of soluble polysulfides and volumetric expansion of sulfur electrodes seriously give rise to the rapid capacity fading and low utilization. In this work, these issues are significantly alleviated by both physically and chemically restricting sulfur species in fluorinated porous triazine-based frameworks (FCTF-S). One-step trimerization of perfluorinated aromatic nitrile monomers with elemental sulfur allows the simultaneous formation of fluorinated triazine-based frameworks, covalent attachment of sulfur and its homogeneous distribution within the pores. The incorporation of electronegative fluorine in frameworks provides a strong anchoring effect to suppress the dissolution and accelerate the conversion of polysulfides. Together with covalent chemical binding and physical nanopore-confinement effects, the FCTF-S demonstrates superior electrochemical performances, as compared to those of the sulfur-rich covalent triazine-based framework without fluorine (CTF-S) and porous carbon delivering only physical confinement. Our approach demonstrates the potential of regulating lithium-sulfur battery performances at a molecular scale promoted by the porous organic polymers with a flexible design. PMID- 28990392 TI - Highly Specific and Wide Range NO2 Sensor with Color Readout. AB - We present a simple and inexpensive method to implement a Griess-Saltzman-type reaction that combines the advantages of the liquid phase method (high specificity and fast response time) with the benefits of a solid implementation (easy to handle). We demonstrate that the measurements can be carried out using conventional RGB sensors; circumventing all the limitations around the measurement of the samples with spectrometers. We also present a method to optimize the measurement protocol and target a specific range of NO2 concentrations. We demonstrate that it is possible to measure the concentration of NO2 from 50 ppb to 300 ppm with high specificity and without modifying the Griess-Saltzman reagent. PMID- 28990393 TI - An Assessment of the Burden on Polish Caregivers of Patients With Dementia: A Preliminary Study. AB - INTRODUCTION: The aim of the study was to assess the level of burden of caregivers of persons with dementia and to analyze the factors related to the sense of burden. METHODS: The study group consisted of 58 caregivers with an average age of 54.7 (+/- 12.6) and 45 (78%) were women. The Caregiver Burden Scale, the Beck Depression Inventory (BDI), the Berlin Social Support Scale (BSSS), and the Satisfaction with Life Scale (SWLS) were used. RESULTS: In the study group, 93% could rely on help in caring for the patient, provided mainly by the family. Most caregivers demonstrated a medium level of burden (2.63 +/- 0.61). A significant correlation was found between the level of caregiver burden and caregiving frequency, BSSS, BDI, and SWLS. CONCLUSIONS: A lot of factors influence the caregivers' burden. It appears necessary to take into consideration the cultural, religious, and economic distinctiveness of the country in question. PMID- 28990394 TI - Striving for Positive Aging Among Chinese Older People: Effects of Life Stress and Control Beliefs in a Longitudinal Study. AB - We examined effects of life stress and control beliefs on a constellation of subjective indicators of well-being for older people, including meaning in life, happiness, peace of mind, and positive aging perception. The Chinese cultural background provided the sociocultural milieu for the present study. In a longitudinal study, 301 older Chinese adults completed a questionnaire survey twice, 6 months apart. Regression analyses found that stress caused by major life changing events (acute) and financial hardship (chronic) were consistent negative predictors of all well-being indicators. Furthermore, primary control belief (tenacious goal pursuit) amplified the negative impacts of life events on happiness and peace of mind. Secondary control belief (submitting to circumstances), in contrast, acted as a buffer that alleviated the deleterious effects of financial hardship on peace of mind and meaning in life. Noting the threats of unfavorable life circumstances and the potency of secondary control belief for older Chinese people, theoretical and cultural implications were discussed. PMID- 28990395 TI - An Evaluation of Reach for a Work Site Implementation of the National Diabetes Prevention Program Focusing on Diet and Exercise. AB - PURPOSE: Our objective is to evaluate the "reach" component of the Reach Effectiveness Adoption Implementation Maintenance (RE-AIM) framework by comparing prediabetics who were and were not interested in enrolling in a free work site diabetes prevention program (DPP) during the first year of the program. Reach is defined as the proportion of eligible participants who enroll in a health program. DESIGN: A cross-sectional study design was used. SETTING: The setting was a large health system in the Midwest. PARTICIPANTS: Prediabetic health plan enrollees and spouses (N = 2158). MEASURES: An online health survey, annual voluntary biometric screenings delivered by a trained health-care professional using standardized protocols via point-of-care testing, and records from the DPP office were the sources of data for this study. ANALYSIS: Health behaviors and biometric screening results were simultaneously compared using multivariable logistic regression. RESULTS: The study population was 63% female, 79% white, and 16% black, and the mean age was 50.2 years (SD = 10.2). The reach of this program was 10%. Prediabetics were more likely to express interest in the DPP, if they were female (adjusted odds ratio [AOR]: 2.4; 95% confidence interval [95% CI]: 1.55-3.72; P < .001), black (AOR = 2.23; 95% CI: 1.43-3.47; P < .001), older in age (AOR: 1.08; 95% CI: 0.99-1.17; P = .05), or had a high-risk waist circumference (AOR = 1.44; 95% CI: 0.98-2.13; P = .07), lower self-efficacy to make healthy changes (AOR = 0.48; 95% CI: 0.26-0.91; P = .03), and 5 or more doctor visits in the last year (AOR = 2.13; 95% CI: 0.99-4.57; P = .05), after controlling for other covariates. CONCLUSION: Current recruitment and implementation strategies are reaching only a small group of individuals who are not representative of the larger prediabetic population. These findings inform future engagement strategies, and we recommend that public health practitioners evaluate reach to ensure that health promotion programs are of high value. PMID- 28990397 TI - Examining the Role of Primary Care Physicians and Challenges Faced When Their Patients Transition to Home Hospice Care. AB - BACKGROUND: The transition into home hospice care is often a critical time in a patient's medical care. Studies have shown patients and caregivers desire continuity with their physicians at the end of life (EoL). However, it is unclear what roles primary care physicians (PCPs) play and what challenges they face caring for patients transitioning into home hospice care. OBJECTIVES: To understand PCPs' experiences, challenges, and preferences when their patients transition to home hospice care. DESIGN: Nineteen semi-structured phone interviews with PCPs were conducted. Study data were analyzed using standard qualitative methods. PARTICIPANTS: Participants included PCPs from 3 academic group practices in New York City. Measured: Physician recordings were transcribed and analyzed using content analysis. RESULTS: Most PCPs noted that there was a discrepancy between their actual role and ideal role when their patients transitioned to home hospice care. Primary care physicians expressed a desire to maintain continuity, provide psychosocial support, and collaborate actively with the hospice team. Better establishment of roles, more frequent communication with the hospice team, and use of technology to communicate with patients were mentioned as possible ways to help PCPs achieve their ideal role caring for their patients receiving home hospice care. CONCLUSIONS: Primary care physicians expressed varying degrees of involvement during a patient's transition to home hospice care, but many desired to be more involved in their patient's care. As with patients, physicians desire to maintain continuity with their patients at the EoL and solutions to improve communication between PCPs, hospice providers, and patients need to be explored. PMID- 28990398 TI - Assessing the Knowledge, Attitudes, and Practices on Antibiotics Among the General Public Attending the Outpatient Pharmacy Units of Hospitals in Bhutan: A Cross-Sectional Survey. AB - We assessed the level of knowledge, attitudes, and practices on antibiotics through a questionnaire-based cross-sectional survey among the general public in Bhutan. Of the 692 participants, 52.6% (364) were females with a mean age of 34.2 years. More than half of the respondents showed unsatisfactory knowledge varying significantly from 23.1% to 69.6%. Cotrimoxazole (septran) was the least known while amoxicillin was the most known antibiotics assessed. Two-thirds of the responsents (267) knew that inappropriate use of antibiotics could lead to antimicrobial resistance and 89% (319) were aware of the need to complete the antibiotic courses. In bivariate analysis, satisfactory knowledge was associated with the education level of graduate and higher as compared with no education. This study revealed unsatisfactory knowledge and attitude but satisfactory practices on antibiotics use among participants. Efforts are needed to improve public awareness on antibiotics. Enforcement of regulations on sale of antibiotics over the counter needs a revamp. PMID- 28990396 TI - Physicians Perceptions of Shared Decision-Making in Neonatal and Pediatric Critical Care. AB - BACKGROUND: Most children die in neonatal and pediatric intensive care units after decisions are made to withhold or withdraw life-sustaining treatments. These decisions can be challenging when there are different views about the child's best interest and when there is a lack of clarity about how best to also consider the interests of the family. OBJECTIVE: To understand how neonatal and pediatric critical care physicians balance and integrate the interests of the child and family in decisions about life-sustaining treatments. METHODS: Semistructured interviews were conducted with 22 physicians from neonatal, pediatric, and cardiothoracic intensive care units in a single quaternary care pediatric hospital. Transcribed interviews were analyzed using content and thematic analysis. RESULTS: We identified 3 main themes: (1) beliefs about child and family interests; (2) disagreement about the child's best interest; and (3) decision-making strategies, including limiting options, being directive, staying neutral, and allowing parents to come to their own conclusions. Physicians described challenges to implementing shared decision-making including unequal power and authority, clinical uncertainty, and complexity of balancing child and family interests. They acknowledged determining the level of engagement in shared decision-making with parents (vs routine engagement) based on their perceptions of the best interests of the child and parent. CONCLUSIONS: Due to power imbalances, families' values and preferences may not be integrated in decisions or families may be excluded from discussions about goals of care. We suggest that a systematic approach to identify parental preferences and needs for decisional roles and information may reduce variability in parental involvement. PMID- 28990399 TI - The Carrel patch clamp for renal transplantation. PMID- 28990400 TI - 'Trust me, I'm a doctor': a qualitative study of the role of paternalism and older people in decision-making when they have lost their capacity. AB - OBJECTIVE: The objective of this study was to explore whether older people want their doctors to make treatment decisions on their behalf when they no longer have capacity to do so, and their reasons for these preferences. METHOD: A convenience sample of older people from two retirement villages were interviewed and asked to respond to a hypothetical vignette. Their responses were analysed using qualitative thematic methodology. RESULTS: Thirty-seven people (56.8% female; mean age = 83.9 years; mean Mini Mental State Examination = 26.5) participated; 73.0% indicated that they would want their doctor to make treatment decisions on their behalf. Three key themes emerged: 1) trust in the doctor patient relationship; 2) doctor-derived factors: knowledge and expertise, professionalism, role and responsibility; 3) patient-derived factors: vulnerability, dependence and reliance, compromised autonomy. CONCLUSION: Our findings suggest that the paternalistic model within medical care can be an expectation of some older patients and if taking a paternalistic approach we should not underestimate the trust and power that is imparted to us. PMID- 28990401 TI - Reactive Oxygen Species and Their Implications on CD4+ T Cells in Type 1 Diabetes. AB - SIGNIFICANCE: Previous work has indicated that type 1 diabetes (T1D) pathology is highly driven by reactive oxygen species (ROS). One way in which ROS shape the autoimmune response demonstrated in T1D is by promoting CD4+ T cell activation and differentiation. As CD4+ T cells are a significant contributor to pancreatic beta cell destruction in T1D, understanding how ROS impact their development, activation, and differentiation is critical. Recent Advances: CD4+ T cells themselves generate ROS via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase expression and electron transport chain activity. Moreover, T cells can also be exposed to exogenous ROS generated by other immune cells (e.g., macrophages and dendritic cells) and beta cells. Genetically modified animals and ROS inhibitors have demonstrated that ROS blockade during activation results in CD4+ T cell hyporesponsiveness and reduced diabetes incidence. Critical Issues and Future Directions: Although the majority of studies with regard to T1D and CD4+ T cells have been done to examine the influence of redox on CD4+ T cell activation, this is not the only circumstance in which a T cell can be impacted by redox. ROS and redox have also been shown to play roles in CD4+ T cell-related tolerogenic mechanisms, including thymic selection and regulatory T cell-mediated suppression. However, the effect of these mechanisms with respect to T1D pathogenesis remains elusive. Therefore, pursuing these avenues may provide valuable insight into the global role of ROS and redox in autoreactive CD4+ T cell formation and function. PMID- 28990403 TI - Redox Potential and ROS-Mediated Nanomedicines for Improving Cancer Therapy. AB - SIGNIFICANCE: The overabundance of reactive oxygen species (ROS) and antioxidants in cancer cells represents a challenge for therapeutic intervention, while also providing an opportunity for the development of new strategies to improve clinical therapeutic outcomes. Recent Advances: Nanotechnology has advanced tremendously in recent decades and now offers many potential opportunities to leverage altered redox status to improve conventional therapies. Highly tunable nanoparticle delivery systems have shown great promise for improving the following: (i) chemotherapy via selective redox-sensitive drug release in tumor cells and limited systemic toxicity; (ii) photodynamic therapy via enhancing photoactivation and/or ROS production; and (iii) radiation therapy via enhancing ROS production. Great progress has also been made regarding novel nanoparticle mediated therapies to enhance tumor cell death via ROS generation and angiogenic inhibition. CRITICAL ISSUES: Current anticancer therapies are limited by systemic side effects and resistance. The inherent heterogeneity and hypoxic status of solid tumors impose significant barriers for even the most rationally designed nanoparticle systems. In addition, few comprehensive biodistribution and toxicity evaluations exist, and clinical efficacy remains to be established. The practicality of many nanoparticle systems is compromised by variable in vivo responses and scale-up difficulties due to complicated chemistry and prohibitive manufacturing costs. FUTURE DIRECTIONS: As nanoparticle design continues to advance, improved therapeutic efficacy will likely follow. Actively targeted systems may improve distribution specificity but more positive clinical demonstrations are needed. Further investigation into systemic and intracellular distribution as well as toxicity will improve understanding of how these nanoparticle systems can be applied to improve existing therapies. Antioxid. Redox Signal. 00, 000-000. PMID- 28990404 TI - Dietary planning, self-efficacy, and outcome expectancies play a role in an online intervention on fruit and vegetable consumption. AB - OBJECTIVE: An online intervention to improve fruit and vegetable (FV) intake examines the role of planning, outcome expectancies, self-efficacy and gender. Women are not only expected to eat more FV than men, but they are also expected to be more responsive to nutritional advice and benefit more from treatment. METHOD: A two-arm digital intervention with 269 men and 395 women (Mage = 41.2, SDage = 11.45; range: 19-66 years) was conducted in Italy, Spain and Greece, followed up at three and six months, comparing a static with a dynamic, feedback intensive platform. RESULTS: Linear mixed models yielded an increase in FV consumption in both the dynamic and the static intervention arms. In men, outcome expectancies were positively related to follow-up FV intake. Dietary planning interacted with self-efficacy on behavioural outcomes. CONCLUSION: FV intake increased overall, and being a woman and involvement in planning facilitated behaviour change. Women seemed to be more engaged in the dynamic platform resulting in a higher amount of planning. Initial motivation, as indicated by outcome expectancies, seemed to be beneficial for men. Self-efficacious individuals benefitted from their engagement in planning, but self-efficacy did not compensate for failing to plan. PMID- 28990402 TI - Reassessing the Structure and Function Relationship of the O2 Sensing Transcription Factor FNR. AB - SIGNIFICANCE: The Escherichia coli regulatory protein fumarate nitrate reduction (FNR) mediates a global transcriptional response upon O2 deprivation. Spanning nearly 40 years of research investigations, our understanding of how FNR senses and responds to O2 has considerably progressed despite a lack of structural information for most of that period. This knowledge has established the paradigm for how facultative anaerobic bacteria sense changes in O2 tension. Recent Advances: Recently, the X-ray crystal structure of Aliivibrio fischeri FNR with its [4Fe-4S] cluster cofactor was solved and has provided valuable new insight into FNR structure and function. These findings have alluded to the conformational changes that may occur to alter FNR activity in response to O2. CRITICAL ISSUES: Here, we review the major features of this structure in context of previously acquired data. In doing so, we discuss additional mechanistic aspects of FNR function that warrant further investigation. FUTURE DIRECTIONS: To complement the [4Fe-4S]-FNR structure, the structures of apo-FNR and FNR bound to DNA or RNA polymerase are needed. Together, these structures would elevate our understanding of how ligation of its [4Fe-4S] cluster allows FNR to regulate transcription according to the level of environmental O2. PMID- 28990405 TI - Suicide of Australians during the Vietnam War. AB - OBJECTIVES: National suicide rates fall during times of war. This fits with the notion of the population coming together against a common foe. But, what happens in the case of a war which is not fully supported, which draws the population and families apart? We consider this question by examining the Australian suicide rates during the divisive Vietnam War. METHODS: We graphed and examined the Australian suicide figures for 1921-2010. RESULTS: We found clear evidence of a decrease in the suicide rate for World War II (consistent with other studies), but a marked elevation of suicide during the Vietnam War. CONCLUSIONS: The elevation of the Australian suicide rate during the Vietnam War is consistent with Durkheim's social integration model - when social integration is lessened, either by individual characteristics or societal characteristics, the risk of suicide rises. PMID- 28990407 TI - Clinical research in an academic psychiatry department: some general principles and case studies. AB - OBJECTIVE: This paper gives guidance for developing collaborative clinical research within an academic psychiatry department. METHODS: We describe the experience at the Australian National University Medical School, and present three case studies. RESULTS: The results reveal that general principles include, but are not limited to, intellectual curiosity, mentorship, collaboration and protected time. CONCLUSIONS: We conclude that a particular strength of a new research department at a medical school may be close collaborative research within clinical settings. PMID- 28990408 TI - A systematic review of electronic assistive technology within supporting living environments for people with dementia. AB - Health and social care provision needs to change in order to meet the needs of an increase in the number of people living with dementia. Environmental design, technology and assistive devices have the potential to complement care, help address some of the challenges presented by this growing need and impact on the lived experience of this vulnerable population. This systematic review was undertaken to identify the research on the use of electronic assistive technology within long-term residential care settings. A total of 3229 papers published from the inception of each of the databases up until May 2016 were retrieved from searches in four major databases. Sixty-one were identified to be included in the review. The inclusion criteria were: original peer reviewed journals; an electronic assistive technology intervention; with residents or tenants living with dementia or their family or paid caregivers; in supported living environments or residential care. The data extracted from the included studies focused on the methodology, technology, outcomes and the role of people living with dementia within the research. Overall, an extensive variety of technical interventions were found, with a broad range of methodological heterogeneity to explore their effect. Additionally, wide-spanning outcomes to support the potential of technology solutions and the challenges presented by such intervention were found. PMID- 28990406 TI - In Vivo Application of Proton-Electron Double-Resonance Imaging. AB - SIGNIFICANCE: Proton-electron double-resonance imaging (PEDRI) employs electron paramagnetic resonance irradiation with low-field magnetic resonance imaging so that the electron spin polarization is transferred to nearby protons, resulting in higher signals. PEDRI provides information about free radical distribution and, indirectly, about the local microenvironment such as partial pressure of oxygen (pO2), tissue permeability, redox status, and acid-base balance. Recent Advances: Local acid-base balance can be imaged by exploiting the different resonance frequency of radical probes between R and RH+ forms. Redox status can also be imaged by using the loss of radical-related signal after reduction. These methods require optimized radical probes and pulse sequences. CRITICAL ISSUES: High-power radio frequency irradiation is needed for optimum signal enhancement, which may be harmful to living tissue by unwanted heat deposition. Free radical probes differ depending on the purpose of PEDRI. Some probes are less effective for enhancing signal than others, which can reduce image quality. It is so far not possible to image endogenous radicals by PEDRI because low concentrations and broad line widths of the radicals lead to negligible signal enhancement. FUTURE DIRECTIONS: PEDRI has similarities with electron paramagnetic resonance imaging (EPRI) because both techniques observe the EPR signal, directly in the case of EPRI and indirectly with PEDRI. PEDRI provides information that is vital to research on homeostasis, development of diseases, or treatment responses in vivo. It is expected that the development of new EPR techniques will give insights into novel PEDRI applications and vice versa. Antioxid. Redox Signal. 28, 1345-1364. PMID- 28990409 TI - HIV primary care by the infectious disease physician in the United States - extending the continuum of care. AB - Models of care for people living with HIV (PLWH) have varied over time due to long term survival, development of HIV-associated non-AIDS conditions, and HIV specific primary care guidelines that differ from those of the general population. The objectives of this study are to assess how often infectious disease (ID) physicians provide primary care for PLWH, assess their practice patterns and barriers in the provision of primary care. We used a 6-item survey electronically distributed to ID physician members of Emerging Infections Network (EIN). Of the 1248 active EIN members, 644 (52%) responded to the survey. Among the 644 respondents, 431 (67%) treated PLWH. Of these 431 responders, 326 (75%) acted as their primary care physicians. Responders who reported always/mostly performing a screening assessment as recommended per guidelines were: (1) Screening specific to HIV (tuberculosis 95%, genital chlamydia/gonorrhoea 77%, hepatitis C 67%, extra genital chlamydia/gonorrhoea 47%, baseline anal PAP smear for women 36% and men 34%); (2) Primary care related screening (fasting lipids 95%, colonoscopy 95%, mammogram 90%, cervical PAP smears 88%, depression 57%, osteoporosis in postmenopausal women 55% and men >50 yrs 33%). Respondents who worked in university hospitals, had <5 years of ID experience, and those who cared for more PLWH were most likely to provide primary care to all or most of their patients. Common barriers reported include: refusal by patient (72%), non adherence to HIV medications (43%), other health priorities (44%), time constraints during clinic visit (43%) and financial/insurance limitations (40%). Most ID physicians act as primary care providers for their HIV infected patients especially if they are recent ID graduates and work in university hospitals. Current screening rates are suboptimal. Interventions to increase screening practices and to decrease barriers are urgently needed to address the needs of the aging HIV population in the United States. PMID- 28990410 TI - Proceedings of the Canadian Society for Exercise Physiology Annual General Meeting - Back to the Beginning / Compte rendu du congres annuel de la Societe canadienne de physiologie de l'exercice - " Back to the Beginning ". PMID- 28990411 TI - Differences in illness perception between children with cancer and other chronic diseases and their parents. AB - BACKGROUND: The purpose of this study was to explore the differences in illness perception between children with cancer and other chronic diseases. A secondary aim was to examine the similarities and differences between the illness perception of these children and their parents. METHODS: The Revised Illness Perception Questionnaire (IPQ-R) was used to measure the children's and parents' illness perceptions. In this study, 184 children (ages 8-18 years) and their caregivers completed the questionnaires. RESULTS: This study shows that children with cancer feel that they have greater control over their treatment compared to the other two groups. The children's parents have more pessimistic views of the illness than their children. CONCLUSION: Examinations of illness perceptions among paediatric cancer patients and their families are essential in designing psychosocial interventions for these families. The clinical value of our results can help better understand the cancer-specific features of illness perceptions. PMID- 28990412 TI - Structural Biology of Proline Catabolic Enzymes. AB - SIGNIFICANCE: Proline catabolism refers to the 4-electron oxidation of proline to glutamate catalyzed by the enzymes proline dehydrogenase (PRODH) and l-glutamate gamma-semialdehyde dehydrogenase (GSALDH, aka ALDH4A1). These enzymes and the intermediate metabolites of the pathway have been implicated in tumor growth and suppression, metastasis, hyperprolinemia metabolic disorders, schizophrenia susceptibility, life span extension, and pathogen virulence and survival. In some bacteria, PRODH and GSALDH are combined into a bifunctional enzyme known as proline utilization A (PutA). PutAs are not only virulence factors in some pathogenic bacteria but also fascinating systems for studying the coordination of metabolic enzymes via substrate channeling. Recent Advances: The past decade has seen an explosion of structural data for proline catabolic enzymes. This review surveys these structures, emphasizing protein folds, substrate recognition, oligomerization, kinetic mechanisms, and substrate channeling in PutA. CRITICAL ISSUES: Major unsolved structural targets include eukaryotic PRODH, the complex between monofunctional PRODH and monofunctional GSALDH, and the largest of all PutAs, trifunctional PutA. The structural basis of PutA-membrane association is poorly understood. Fundamental aspects of substrate channeling in PutA remain unknown, such as the identity of the channeled intermediate, how the tunnel system is activated, and the roles of ancillary tunnels. FUTURE DIRECTIONS: New approaches are needed to study the molecular and in vivo mechanisms of substrate channeling. With the discovery of the proline cycle driving tumor growth and metastasis, the development of inhibitors of proline metabolic enzymes has emerged as an exciting new direction. Structural biology will be important in these endeavors. Antioxid. Redox Signal. 00, 000-000. PMID- 28990413 TI - NADPH Oxidases and Their Roles in Skin Homeostasis and Carcinogenesis. AB - SIGNIFICANCE: Skin protects the body from dehydration, pathogens, and external mutagens. NADPH oxidases are central components for regulating the cellular redox balance. There is increasing evidence indicating that reactive oxygen species (ROS) generated by members of this enzyme family play important roles in the physiology and pathophysiology of the skin. Recent Advances: NADPH oxidases are active producers of ROS such as superoxide and hydrogen peroxide. Different isoforms are found in virtually all tissues. They play pivotal roles in normal cell homeostasis and in the cellular responses to various stressors. In particular, these enzymes are integral parts of redox-sensitive prosurvival and proapoptotic signaling pathways, in which they act both as effectors and as modulators. However, continuous (re)activation of NADPH oxidases can disturb the redox balance of cells, in the worst-case scenario in a permanent manner. Abnormal NADPH oxidase activity has been associated with a wide spectrum of diseases, as well as with aging and carcinogenesis. CRITICAL ISSUES: Sunlight with its beneficial and deleterious effects induces the activation of NADPH oxidases in the skin. Evidence for the important roles of this enzyme family in skin cancer and skin aging, as well as in many chronic skin diseases, is now emerging. FUTURE DIRECTIONS: Understanding the precise roles of NADPH oxidases in normal skin homeostasis, in the cellular responses to solar radiation, and during carcinogenesis will pave the way for their validation as therapeutic targets not only for the prevention and treatment of skin cancers but also for many other skin-related disorders. Antioxid. Redox Signal. 28, 1238-1261. PMID- 28990414 TI - Biomarkers of Endothelial, Renal, and Platelet Dysfunction in Stage 5 Chronic Kidney Disease Hemodialysis Patients With Heart Failure. AB - The aim of this study was to determine the role of endothelial, renal, and inflammatory biomarkers in the pathogenesis of heart failure (HF) in patients with stage 5 chronic kidney disease (CKD5) undergoing maintenance hemodialysis (HD). Plasma levels of biomarkers-kidney injury molecule 1 (KIM-1), N-terminal pro brain natriuretic peptide (NT-proBNP), glycated hemoglobin, neutrophil gelatinase-associated lipocalin, interleukin-18,platelet-derived growth factor, platelet factor 4 (PF4), 25-OH vitamin D, parathyroid hormone (PTH), endothelin, and endocan-were measured in CKD5-HD patients at the Loyola University Ambulatory Dialysis facility. The HF (+) CKD5-HD patients, as compared to HF (-) CKD5-HD patients, exhibited significantly elevated NT-proBNP ( P = .0194) and KIM-1 ( P = .0485). The NT-proBNP in HF (+) CKD5-HD patients was found to correlate with the levels of serum potassium ( P = .023, R = -.39), calcium ( P = .029, R = -.38), and PF4 ( P = .045, R = -.35). The KIM-1 in HF (+) CKD5-HD patients was found to correlate with PTH ( P = .043, R = -.36) and 25-OH vitamin D ( P = .037, R = .36). Elevated plasma NT-proBNP and KIM-1 in CKD5-HD and HF (+) CKD5-HD patients suggest that natriuretic peptides and KIM-1 may contribute to the pathogenesis of HF in CKD5-HD patients. PMID- 28990416 TI - Does Regular Physical Exercise Preserve Artery Dilation by Lowering Nox2-Related Oxidative Stress? AB - Habitual physical activity has beneficial effects on cardiovascular risk reduction by improving vascular function but the underlying mechanism is still unclear. To address this issue, we performed a cross-sectional study comparing 50 physically active (PA) adults with 50 sedentary controls matched for age, sex, and cardiovascular risk factors. PA subjects had significantly higher flow mediated dilation (FMD) than controls and higher serum levels of nitrite/nitrate, a marker of nitric oxide generation. In addition, PA subjects showed lower levels of urinary isoprostanes, a marker of reactive oxygen species (ROS) production, and lower serum levels of sNox2-dp, a validated assay to measure Nox2 activity, one of the most important enzymes producing ROS in the blood cells. FMD was independently correlated with sNox2-dp, after adjusting for possible confounding factors. Our observation leads to the hypothesis that, in adults, regular exercise preserves artery dilation through Nox2 decreased activity. Antioxid. Redox Signal. 28, 1576-1581. PMID- 28990417 TI - Risk indicators and effects of hypertension on HIV/AIDS disease progression among patients seen at Kenyatta hospital HIV care center. AB - There is paucity of data on prevalence of hypertension and its effects on HIV/AIDS progression among patients at Kenyatta National Hospital (KNH), Kenya. This was a cross sectional study conducted between January and May 2015 at the KNH HIV Care Centre. Ethical approval was obtained from institutional ethics review board. HIV positive adult patients were recruited sequentially, and written informed consent obtained from each participant. Systematic sampling was used to select participants who were screened for blood pressure, body mass index (BMI) and lifestyle characteristics. Data on clinical parameters were extracted from patient records. A total of 297 participants (89 males and 208 females) were enrolled in the study. The participants were socially diverse in cultural beliefs, religious practices and lifestyles. Their ages ranged from 30 to 57 years, and the average age of males (M = 44.56, SD = 6.05) was higher than females (M = 42.29, SD = 6.16), p < .01. The prevalence of hypertension was found to be 23.2%. The relation between CD4 counts and creatinine was statistically significant, p < .01, as was the association between CD4 counts and BMI, p < .01. Hypertension is a highly prevalent co-morbidity in HIV patients. The risk factors include prolonged use of ART as well as increased body mass index. The effects of hypertension on HIV progression include low CD4+ T cell counts which complicate the underlying immunosuppression. PMID- 28990415 TI - Redox Regulation of Heme Oxygenase-2 and the Transcription Factor, Rev-Erb, Through Heme Regulatory Motifs. AB - SIGNIFICANCE: Heme binds to and serves as a cofactor for a myriad of proteins that are involved in diverse biological processes. Hemoproteins also exhibit varying modes of heme binding, suggesting that the protein environment contributes to the functional versatility of this prosthetic group. The subject of this review is a subset of hemoproteins that contain at least one heme regulatory motif (HRM), which is a short sequence containing a Cys-Pro core that, in many cases, binds heme with the Cys acting as an axial ligand. Recent Advances: As more details about HRM-containing proteins are uncovered, some underlying commonalities are emerging, including a role in regulating protein stability. Further, the cysteines of some HRMs have been shown to form disulfide bonds. Because the cysteines must be in the reduced, dithiol form to act as a heme axial ligand, heme binds at these sites in a redox-regulated manner, as demonstrated for heme oxygenase-2 (HO2) and Rev-erbbeta. CRITICAL ISSUES: HRM containing proteins have wide variations in heme affinity, utilize different axial ligand schemes, and exhibit differences in the ability to act as a redox sensor-all while having a wide variety of biological functions. Here, we highlight HO2 and Rev-erbbeta to illustrate the similarities and differences between two hemoproteins that contain HRMs acting as redox sensors. FUTURE DIRECTIONS: HRMs acting as redox sensors may be applicable to other HRM containing proteins as many contain multiple HRMs and/or other cysteine residues, which may become more evident as the functional significance of HRMs is probed in additional proteins. PMID- 28990418 TI - Redox Mechanisms in Migraine: Novel Therapeutics and Dietary Interventions. AB - SIGNIFICANCE: Migraine represents the third most prevalent and the seventh most disabling human disorder. Approximately 30% of migraine patients experience transient, fully reversible, focal neurological symptoms (aura) preceding the attack. Recent Advances: Awareness of the hypothesis that migraine actually embodies a spectrum of illnesses-ranging from episodic to chronic forms-is progressively increasing and poses novel challenges for clarifying the underlying pathophysiological mechanisms of migraine as well as for the development of novel therapeutic interventions. Several theories have evolved to the current concept that a combination of genetic, epigenetic, and environmental factors may play a role in migraine pathogenesis, although their relative importance is still being debated. CRITICAL ISSUES: One critical issue that deserves a particular attention is the role of oxidative stress in migraine. Indeed, potentially harmful oxidative events occur during the migraine attack and long-lasting or frequent migraine episodes may increase brain exposure to oxidative events that can lead to chronic transformation. Moreover, a wide variety of dietary, environmental, physiological, behavioral, and pharmacological migraine triggers may act through oxidative stress, with clear implications for migraine treatment and prophylaxis. Interestingly, almost all current prophylactic migraine agents exert antioxidant effects. FUTURE DIRECTIONS: Increasing awareness of the role of oxidative stress and/or decreased antioxidant defenses in migraine pathogenesis and progression to a chronic condition lays the foundations for the design of novel prophylactic approaches, which, by reducing brain oxidative phenomena, could favorably modify the clinical course of migraine. Antioxid. Redox Signal. 28, 1144-1183. PMID- 28990419 TI - Proline Metabolism in Cell Regulation and Cancer Biology: Recent Advances and Hypotheses. AB - SIGNIFICANCE: It is increasingly clear that proline metabolism plays an important role in metabolic reprogramming, not only in cancer but also in related fields such as aging, senescence, and development. Although first focused on proline catabolism, recent studies from a number of laboratories have emphasized the regulatory effects of proline synthesis and proline cycling. Recent Advances: Although proline dehydrogenase/proline oxidase (PRODH/POX) has been known as a tumor protein 53 (P53)-activated source of redox signaling for initiating apoptosis and autophagy, senescence has been added to the responses. On the biosynthetic side, two well-recognized oncogenes, c-MYC and phosphoinositide 3 kinase (PI3K), markedly upregulate enzymes of proline synthesis; mechanisms affected include augmented redox cycling and maintenance of pyridine nucleotides. The reprogramming has been shown to shift in clonogenesis and/or metastasis. CRITICAL ISSUES: Although PRODH/POX generates reactive oxygen species (ROS) for signaling, the cellular endpoint is variable and dependent on metabolic context; the switches for these responses remain unknown. On the synthetic side, the enzymes require more complete characterization in various cancers, and demonstration of coupling of proline metabolites to other pathways may require studies of protein-protein interactions, membrane transporters, and shuttles. FUTURE DIRECTIONS: The proline metabolic axis can serve as a scaffold on which a variety of regulatory mechanisms are integrated. Once understood as a central mechanism in cancer metabolism, proline metabolism may be a good target for adjunctive cancer therapy.-Antioxid. Redox Signal. 00, 000-000. PMID- 28990420 TI - Synaptic Activity Protects Neurons Against Calcium-Mediated Oxidation and Contraction of Mitochondria During Excitotoxicity. AB - AIMS: Excitotoxicity triggered by extrasynaptic N-methyl-d-aspartate-type glutamate receptors has been implicated in many neurodegenerative conditions, including Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis, and stroke. Mitochondrial calcium overload leading to mitochondrial dysfunction represents an early event in excitotoxicity. Neurons are rendered resistant to excitotoxicity by previous periods of synaptic activity that activates a nuclear calcium-driven neuroprotective gene program. This process, termed acquired neuroprotection, involves transcriptional repression of the mitochondrial calcium uniporter leading to a reduction in excitotoxcity associated mitochondrial calcium load. As mitochondrial calcium and the production of reactive oxygen species may be linked, we monitored excitotoxicity associated changes in the mitochondrial redox status using the ratiometric glutathione redox potential indicator, glutaredoxin 1 (GRX1)-redox-sensitive green fluorescent protein (roGFP)2, targeted to the mitochondrial matrix. Aim of this study was to investigate if suppression of oxidative stress underlies mitoprotection afforded by synaptic activity. RESULTS: We found that synaptic activity protects primary rat hippocampal neurons against acute excitotoxicity induced mitochondrial oxidative stress and mitochondrial contraction associated with it. Downregulation of the mitochondrial uniporter by genetic means mimics the protective effect of synaptic activity on mitochondrial redox status. These findings indicate that oxidative stress acts downstream of mitochondrial calcium overload in excitotoxicity. Innovation and Conclusion: We established mito-GRX1 roGFP2 as a reliable and sensitive tool to monitor rapid redox changes in mitochondria during excitotoxicity. Our results highlight the importance of developing means of blocking mitochondrial calcium overload for therapeutic targeting of oxidative stress and mitochondrial dysfunction in neurodegenerative diseases. Antioxid. Redox. Signal. 29, 1109-1124. PMID- 28990421 TI - The impact of a private-public partnership delivery system on the HIV continuum of care in a South Indian city. AB - We characterized the impact of a Private-Public Partnership (PPP) on the continuum of HIV care (e.g., treatment initiation, ART effectiveness and loss to follow-up) among adults enrolled at a private hospital/ART link center in the southern state of Karnataka, India from 2007 through 2012. Data on 2326 adults in care were compiled using an electronic database supplemented with medical chart abstraction. Survival methods with staggered entries were used to analyze time to ART initiation and loss to follow-up as well as associated factors. Mixed effects linear regression models were used to assess ART effectiveness. The mean age of adults in care was 36 years; 40% were male. The majority were married, had less than primary education, and less than 45 US dollars (3000 Indian Rupee) monthly income. The mean CD4 at presentation was 527 cells/mm3. The median time from ART eligibility to initiation was 5 and 2 months for before and after the PPP, respectively (p < 0.001). Becoming eligible after PPP was associated with more rapid treatment initiation (Hazard Ratio: [95% Confidence Interval] 1.49 [1.11, 1.99]). Moreover, among the 1639 persons lost to follow-up, more rapid loss was observed before the PPP (12.77 months) vs. after (13.37 months) (p = 0.25) and there was a significant interaction between ART status and calendar time before and after the PPP (p < 0.001). Being on treatment was associated with a lower likelihood of becoming lost before the PPP (HR: [95% CI] 0.33 [0.27, 0.42]), but this association was reversed after the PPP (HR: [95% CI] 1.77 [1.54, 2.04]), p value for interaction <0.001. Treatment response measured by CD4 was comparable before and after the PPP (p = 0.088). Our findings suggest that PPP models of ART delivery may improve HIV treatment initiation and loss to follow-up without compromising the effectiveness of treatment. Efforts to expand these system-level interventions should be considered with on-going evaluation. PMID- 28990422 TI - Gait speed has comparable prognostic capability to six-minute walk distance in older patients with cardiovascular disease. AB - Background Although gait speed and six-minute walk distance are used to assess functional capacity in older patients with cardiovascular disease, their prognostic capabilities have not been directly compared. Methods The study population was identified from the Kitasato University Cardiac Rehabilitation Database and consisted of 1474 patients >=60 years old with a mean age of 72.2 +/ 7.1 years that underwent evaluation of both usual gait speed and six-minute walk distance in routine geriatric assessment between 1 June 2008-30 September 2015. Both gait speed and six-minute walk distance were determined on the same day at hospital discharge. Results Mean gait speed and six-minute walk distance in the whole population were 1.04 m/s and 381 m, respectively, and were strongly positively correlated ( r = 0.80, p < 0.001). A total of 180 deaths occurred during a follow-up of 2.3 +/- 1.9 years. After adjusting for confounding factors, both gait speed (adjusted hazard ratio per 0.1 m/s increase: 0.87, 95% confidence interval: 0.81-0.93, p < 0.001) and six-minute walk distance (adjusted hazard ratio per 10-metre increase: 0.96, 95% confidence interval: 0.94-0.97, p < 0.001) were independent predictors of all-cause mortality. There was no significant difference in prognostic capability between gait speed and six-minute walk distance (c-index: 0.64 (95% confidence interval: 0.60-0.69) and 0.66 (95% confidence interval: 0.61-0.70), respectively, p = 0.357). Conclusions Gait speed and six-minute walk distance showed similar prognostic predictive ability for all cause mortality in older cardiovascular disease patients, indicating the potential utility of gait speed as a simple risk stratification tool in older cardiovascular disease patients. PMID- 28990423 TI - Dupilumab for the treatment of asthma. AB - INTRODUCTION: Dupilumab is a fully human IgG4 monoclonal antibody directed against the alpha subunit of the interleukin (IL)-4 receptor (IL-4Ralpha). Since the activation of IL-4Ralpha is utilized by both IL-4 and IL-13 to mediate their pathophysiological effects, dupilumab behaves as a dual antagonist of these two sister cytokines, which blocks IL-4/IL-13-dependent signal transduction. Areas covered: Herein, the authors review the cellular and molecular pathways activated by IL-4 and IL-13, which are relevant to asthma pathobiology. They also review: the mechanism of action of dupilumab, the phase I, II and III studies evaluating the pharmacokinetics as well as the safety, tolerability and clinical efficacy of dupilumab in asthma therapy. Expert opinion: Supported by a strategic mechanism of action, as well as by convincing preliminary clinical results, dupilumab currently appears to be a very promising biological drug for the treatment of severe uncontrolled asthma. It also may have benefits to comorbidities of asthma including atopic dermatitis, chronic sinusitis and nasal polyposis. PMID- 28990424 TI - An Inducible Promoter Responsive to Different Porphyrinogenic Stimuli Improves Gene Therapy Vectors for Acute Intermittent Porphyria. AB - Porphobilinogen deaminase (PBGD) gene therapy represents a promising therapeutic option for acute intermittent porphyria (AIP) patients suffering recurrent acute attacks. A first-in-human Phase I clinical trial confirmed the safety and tolerability of adeno-associated virus (AAV)-AAT-PBGD gene therapy, but higher doses and/or more efficient vectors are needed to achieve therapeutic expression of the transgene. This study assayed the insertion into the promoter of a short enhancer element able to induce transgene expression during exposure to endogenous and exogenous stimuli related to the pathology of the disease. The inclusion in tandem of two elements of the minimal functional sequence of human delta-aminolevulinic acid synthase drug-responsive enhancing sequence (ADRES) positioned upstream of the promoter strongly induced transgene expression in the presence of estrogens, starvation, and certain drugs known to trigger attacks in porphyria patients. The inclusion of two ADRES motives in an AAV vector improved therapeutic efficacy, reducing 10-fold the effective dose in AIP mice. In conclusion, the inclusion of specific enhancer elements in the promoter of gene therapy vectors for AIP was able to overexpress the therapeutic transgene when it is most needed, at the time when porphyrinogenic factors increase the demand for hepatic heme and precipitate acute porphyria attacks. PMID- 28990425 TI - Mendelian forms of disease and age at onset affect survival in frontotemporal dementia. AB - OBJECTIVE: Frontotemporal dementia (FTD) is a common cause of young onset dementia. Very few reports on disease duration are currently available and predictors of survival are still undefined. The aim of the present study was to assess the natural history of FTD and to define predictors of survival. METHODS: Four hundred amd eleven FTD patients, including 294 with behavioural variant FTD, 77 with agrammatic variant primary progressive aphasia (PPA) and 40 with semantic variant PPA, were consecutively enrolled and demographic and clinical variables carefully recorded. Each patient underwent genetic screening for monogenic disease. RESULTS: The mean survival time from onset of the symptoms was 7.8 +/- 4.0 years. The presence of a pathogenic mutation (GRN, C9orf72 or MAPT) (Hazard ratio [HR] = 1.85, 95% CI 1.04-3.31, p = 0.037) and older age at disease onset (HR = 1.04, 95% CI 1.02-1.07, p = 0.002) were associated with shorter life expectancy. However, a significant negative interaction between age at onset and genetic mutation was found, suggesting that the effect of age is different in patients with and without a genetic mutation (p = 0.028). Gender, clinical phenotype or education and occupation were not associated with survival risk. CONCLUSIONS: Our findings suggest that monogenic disease and age at onset are independent predictors of survival and should be considered in future clinical intervention trials and in patients' and caregivers' counselling. PMID- 28990427 TI - Chew on This: Not All First Finger Foods Are Created Equal. AB - The American Academy of Pediatrics (AAP) recommends when to start first finger foods (FFFs) and what types of foods to start with, but it is unclear whether products marketed as FFF comply with these recommendations. We evaluated FFF products for compliance with AAP recommendations and product safety using 41 adult product testers, who were asked to dissolve each product in their mouth. Product characteristics, comments pertaining to product safety, and time to dissolve each product were recorded. Only 2 products met all AAP criteria, and safety concerns were raised for an additional 2 products. One product showed a large change in dissolvability after being left out of original packaging. Consumers should not assume that products marketed for infant/toddler consumption comply with AAP recommendations. Also, products left out of original packaging may change consistency, presenting a choking hazard. Additional research is warranted to guide the development of regulations surrounding labeling and marketing of these foods. PMID- 28990426 TI - Gene Therapy for Modulation of T-Cell-Mediated Immune Response Provoked by Corneal Transplantation. AB - Corneal transplantation (keratoplasty) is the most common type of tissue replacement in the world. The increased rate of graft rejection after keratoplasty is a central problem for repeated transplantations and in inflamed host corneas. It has been shown that apoptosis of grafted epithelium has a role in corneal allograft rejection. This study focused on the T-cell response triggered in BALB/c mice after allogeneic corneal transplantation with and without anti-apoptotic p35-transduced epithelium. To restrict p35 expression to the epithelial cells, modified allogeneic composite grafts were created. As a result, it was found that the proportion of alloreactive CD4+ T cells in postoperatively removed cervical lymph nodes was reduced in the p35-transduced group compared to the allogeneic control group. Diminished priming of the CD4+ T cells was supported by significantly decreased proliferation and lower interferon gamma secretion when compared to allogeneic engraftments. The reduced priming of CD4+ lymphocytes is the first confirmation of the functionality of p35 in the epithelium of corneal grafts to alter the development of the recipient's immune response. Thus, modification of allosensibilization seems to be a promising tool for reducing graft-mediated immune response following corneal transplantation. PMID- 28990428 TI - Retrospective Review of Comorbid Conditions in a Multidisciplinary Pediatric Weight Management Clinic. AB - A retrospective medical chart review was conducted of patients enrolled in the Fit for Healthy Weight Clinic (Fit Clinic). At initial evaluation, comorbidities were identified by the patient and pediatrician. The number of comorbidities increased with age among patients. In reviewing the differences among the number of identified comorbidities among grade school age and adolescent patients, increases of 30% were observed in gastrointestinal-associated, 23% in psychiatric, 18% in endocrine, 16% in cardiovascular, and 14% in respiratory comorbidities. Fit Clinic patients already manifest many known obesity-related comorbidities as evidenced in identified conditions and abnormal laboratory values. The elevated blood pressures, blood glucose, and cholesterol levels raise concern for the future development of coronary artery disease and type 2 diabetes mellitus. With an average of five obesity-related comorbidities, Fit Clinic patients already have more comorbidities than what is evidenced in large US population-based studies, demonstrating that solely addressing body mass index is not sufficient. PMID- 28990429 TI - Persistent Cervical Lymphadenopathy Caused by Foreign Body Ingestion With Migration Into Soft Tissue. PMID- 28990430 TI - Utilization of Antipyretics for Nonurgent Fever in a Pediatric Emergency Department. AB - This retrospective cohort study aimed to describe antipyretic use among healthy patients in a pediatric emergency department (ED) with nonurgent fever defined as: triage level 4 or 5, chief complaint fever or temperature 38 degrees C to 39 degrees C, and otherwise normal vital signs, and determine if antipyretic administration is associated with increased ED length of stay (LOS). We compared continuous variables using Kruskal-Wallis and Wilcoxon rank sum testing. We adjusted confounding variables using logistic regression modeling. A total of 22 169 patients were included. Of these, 52% received antipyretic: acetaminophen (38%), ibuprofen (19%), or both antipyretics (5%). ED LOS (median hours) varied by number of antipyretic types given (none, 2.2; ibuprofen, 2.7; acetaminophen, 2.7; and both 3.4, P < .001) and number of doses (0 doses, 2.2, 1 dose, 2.7; 2 doses, 3.4, P < .001). Patients who received antipyretic were more likely to have ED LOS greater than 2 hours (adjusted odds ratio 1.99, 95% CI 1.88-2.11) compared with those with no antipyretic, controlling for age, imaging studies, laboratory studies, antibiotic administration, and disposition. PMID- 28990431 TI - Fever, Abdominal Pain, and Jaundice in a 7-Year-Old Male. PMID- 28990432 TI - Three-Month-Old Girl With Worm Infestation. PMID- 28990433 TI - Serum 25-hydroxyvitamin D status in chinese children with vitiligo: a case control study. AB - BACKGROUND: Vitamin D can play a vital role in autoimmune diseases. Epidemiologic evidence demonstrates vitamin D deficiency excited in adult patients with vitiligo. OBJECTIVES: To investigate 25-hydroxyvitamin D (25(OH)D) levels in children with vitiligo and explore possible relevant factors. METHODS: A total of 114 patients and 100 controls were included in our case-control study. We analyzed the required data collected by the questionnaire and examination to reveal the correlation with 25(OH)D levels. RESULTS: The mean serum 25(OH)D levels in patients and controls were 43.62 +/- 19.23 and 67.87 +/- 19.45 nmol/L, respectively. The rate of deficient in patients and controls are 14.9% and 2%, respectively. There was significant difference between the 2 groups. Significant differences also existed on different ages comparing serum vitamin D levels of patients with controls ( P < .001). Age was an independent factor affecting 25(OH)D level ( P = .032). Two (1.8%) and 4 (3.5%) of children with vitiligo have comorbid autoimmune diseases and family history, respectively. There was no correlation between sex, duration of disease, type of vitiligo, skin lesion location, stage, family history, and comorbid autoimmune diseases with 25(OH)D levels. CONCLUSION: Serum vitamin D level was associated with onset vitiligo children. More sunshine and vitamin D fortified foods are necessary among children with age. The rates of children vitiligo with family history has decreased in China. PMID- 28990434 TI - Therapeutic Effect Evaluation of Neuromuscular Electrical Stimulation With or Without Strengthening Exercise on Spastic Cerebral Palsy. AB - The aims of this study were to investigate the effect of neuromuscular electrical stimulation (NMES) combined with strengthening exercise on movement in children with spastic cerebral palsy (CP). One hundred children with spastic CP were randomly divided into a treatment group (NMES and strengthening exercise, n = 50) and a control group (only NMES, n = 50). We compared the Comprehensive Spasticity Scale (CSS) score, Gross Motor Function Measure (GMFM) score, and walking speed before treatment and 6 weeks and 3 months after treatment between the 2 groups. There was no difference in CSS score between the treatment and control groups before the therapy (12.0 +/- 3.4 vs 12.3 +/- 3.6), which decreased much more in the treatment group after 6 weeks (7.6 +/- 3.0 vs 9.5 +/- 2.8) and 3 months (7.4 +/- 2.4 vs 9.4 +/- 2.6) with significant differences ( P < .05). No difference in GMFM score was observed between the treatment and control groups before the therapy (44.5 +/- 13.2 vs 44.0 +/- 12.6), which increased much more in the treatment group after 6 weeks (70.6 +/- 15.2 vs 56.7 +/- 14.3) and 3 months (71.0 +/- 16.4 vs 58.0 +/- 15.6) with significant differences ( P < .05). The walking speed improved over time, which was the same before the treatment (0.43 +/- 0.13 m/s vs 0.45 +/- 0.14 m/s), and was significantly greater in the treatment group than that in the control group (6 weeks: 0.69 +/- 0.15 m/s vs 0.56 +/- 0.12 m/s, P < .05; 3 months: 0.72 +/- 0.17 m/s vs 0.57 +/- 0.18 m/s, P < .05). NMES combined with strengthening exercise was more effective than NMES alone in the recovery of spastic CP. PMID- 28990435 TI - PTPN22 1858C > T polymorphism and susceptibility to systemic lupus erythematosus: a meta-analysis update. AB - Studies performed in the past years showed PTNP22 1858 C > T (rs2476601) polymorphism as associated with systemic lupus erythematosus susceptibility, although conflicting findings are still found. In this context, a powerful statistical study, such as meta-analysis, is necessary to establish a consensus. The aim of this study was to evaluate association studies between the PTPN22 1858 C > T polymorphism and SLE by a meta-analysis update, including three recently published studies in the last three years. A total of 3868 SLE patients and 7458 healthy individuals were considered herein, enclosing 19 studies from Asian, American, European and Latin ethnic groups. Odds ratio (OR) was performed for allelic, dominant and recessive genetic models. Statistically significant association was found between the PTPN22 1858 C > T polymorphism and susceptibility to SLE in all inheritance models. Allelic genetic model data (OR = 1.54, 95% confidence interval (CI) = 1.38-1.72, p value=.000) shows that T allele confers increased SLE susceptibility. As well as recessive genetic model (OR = 2.04, 95% CI = 1.09-3.82, p value = .030) for T/T genotype. Instead, dominant genetic model shows that C/C genotype confers lower susceptibility for SLE development (OR = 0.62, 95% CI = 0.54-0.72, p value = .000). In addition, we provided an ethnicity-derived meta-analysis. The results showed association in Caucasian (OR = 1.47, p value = .000) and Latin (OR = 2.41, p value = .000) ethnic groups. However, rs2476601 polymorphism is not associated nor in Asian (OR= 1.31; p value = .54) and African (OR = 2.04; p value=.22) populations. In conclusion, present meta-analysis update confirms that T allele and T/T genotype in PTPN22 1858 C > T polymorphism confers SLE susceptibility, particular in Caucasian and Latin groups, suggesting PTPN22 1858 C > T as a potential genetic marker in SLE susceptibility. PMID- 28990436 TI - Acceptability of Implantable Continuous Glucose Monitoring Sensor. AB - BACKGROUND: Real-time continuous glucose monitoring is associated with significant benefits for diabetes management. Implantable sensors could overcome some challenges reportedly associated with device visibility, psychosocial functioning and sensor durability. METHODS: A psychosocial assessment was conducted to determine acceptability and impact of an implantable continuous glucose monitoring (CGM) sensor as part of the PRECISE trial. Questionnaires were administered to participants comprising the Diabetes Distress Scale, the CGM impact scale, and bespoke device satisfaction. RESULTS: Fifty-one participants across the United Kingdom (n = 10) and Germany (n = 41) completed the questionnaires. Of these, 90% had T1D, 50% followed an insulin pump therapy regimen, and 45% of the participants were previous CGM users. CGM Impact Scale results show 86% (n = 44) of participants reported feeling better (14% neutral) about their diabetes control with 90% CGM naive participants and 81% previous CGM users reporting increased confidence about their diabetes management. Furthermore, 73% (n = 37) felt more safe (27% neutral) while sleeping and 78% (n = 39) more confident (22% neutral) about avoiding serious hypoglycemia. Responses correspond with an average improvement in HbA1c from 7.51 to 7.05 ( P < .0001) over the 90 days use of the CGM. Overall, the system was rated highly on ease of use, convenience and comfort. 84% would choose to be inserted again with 93% of CGM naive participants (86% previous CGM users) reporting minimized burden of diabetes. CONCLUSIONS: Implantable CGM devices are acceptable to users and are evaluated favorably. The considerable majority of participants (93% of first time users and 77% previous CGM users) would like to continue using the system to help manage their diabetes more effectively. PMID- 28990437 TI - Impact of Injection Speed, Volume, and Site on Pain Sensation. AB - BACKGROUND: Painful subcutaneous insulin injections may decrease treatment compliance. Improving injection comfort therefore represents a particular area of technological research in which steady progress has been made since the introduction of the insulin pen in 1985. Injection pain can be influenced by many variables, but relatively little is known about their impact. This study investigated the impact of injection volume (range 0-2250 uL), speed (range 0-800 uL/sec), and site (abdomen vs thigh) on pain sensation. METHOD: In random order, patients (n = 80) with type 1 or type 2 diabetes received 24 saline injections subcutaneously through a 27G ultra-thin-wall needle. Injections were performed in the abdomen (n = 19) and thigh (n = 5) with predefined speed-volume combinations. For each injected speed-volume combination, patients scored their pain sensation on a 100 mm visual analog scale (VAS). RESULTS: The mean pain scores for speed volume combinations were all in the lower part (<20 mm) of the VAS, indicating zero to mild pain. Pain sensation was statistically higher ( P < .05) with the 2250 uL volume compared to other injection volumes (range 4.3-5.1 mm) and with thigh compared to abdomen injections (2.1 mm). Pain sensation did not change with increasing injection speed. Patient acceptance of the injection pain was high for all injections (range 93.7-98.7%). CONCLUSIONS: In summary, large volume and thigh injections are rated more painful, but the clinical impact of these findings is likely marginal considering the low absolute pain levels and high patient acceptance rates. Injection speed does not influence pain sensation. PMID- 28990438 TI - Flash Glucose Monitoring: Differences Between Intermittently Scanned and Continuously Stored Data. AB - The flash glucose monitoring system FreeStyle Libre (Abbott Diabetes Care Ltd., Witney, UK) measures interstitial glucose concentrations and continuously stores measurement values every 15 minutes. To obtain a current glucose reading, users have to scan the sensor with the reader. In a clinical trial, 5% of the scanned data showed relative differences of more than +/-10% compared with continuously stored data points (median -0.5%). Such differences might impact results of studies using this system. It should be indicated whether scanned or continuously stored data were used for analyses. Health care professionals might have to differentiate between data reports from clinical software and the scanned data their patients are provided with. Additional information on these differences and their potential impact on therapeutic decisions would be helpful. PMID- 28990439 TI - Effect of Foeniculum vulgare (fennel) on vaginal atrophy in postmenopausal women: A double-blind, randomized, placebo-controlled trial. AB - Objectives This study was conducted to evaluate the effects of orally administered fennel on vaginal atrophy. Materials and methods In this double blind, randomized, placebo-controlled trial, 60 postmenopausal women living in Mashhad, Iran, were randomly divided into an oral fennel group (n = 30) and a placebo group (n = 30). The Maturation Vaginal Index and maturation values were measured once at baseline and again upon a three-month follow-up. Results The paired t-test showed statistically significant changes in the Maturation Vaginal Index (i.e. a decline in the parabasal cells and an increase in the intermediate and superficial cells) and maturation values in both the fennel and placebo groups at the end of the trial compared to at baseline. Nonetheless, no significant differences were observed in the percentages of the parabasal (P = 0.191), intermediate (P = 0.219) and superficial (P = 0.82) cells, which was also the case for the maturation values (P = 0.64). Conclusion Fennel had no significant positive effects on vaginal atrophy in postmenopausal women. Nonetheless, more studies are recommended to be conducted using higher doses of fennel and larger sample sizes so as to verify the results of this study. PMID- 28990440 TI - Influence of Passive Joint Stiffness on Proprioceptive Acuity in Individuals With Functional Instability of the Ankle. AB - Study Design Controlled laboratory study, cross-sectional. Background Deficits in ankle proprioceptive acuity have been reported in persons with functional instability of the ankle. Passive stiffness has been proposed as a possible mechanism underlying proprioceptive acuity. Objective To compare proprioceptive acuity and passive ankle stiffness in persons with and without functional ankle instability, and to assess the influence of passive joint stiffness on proprioceptive acuity in persons with functional ankle instability. Methods A sample of 18 subjects with and 18 without complaints of functional ankle instability following lateral ankle sprain participated. An isokinetic dynamometer was used to compare motion perception threshold, passive position sense, and passive ankle stiffness between groups. To evaluate the influence of passive stiffness on proprioceptive acuity, individuals in the lateral functional ankle instability group were divided into 2 subgroups: "high" and "low" passive ankle stiffness. Results The functional ankle instability group exhibited increased motion perception threshold when compared with the corresponding limb of the control group. Between-group differences were not found for passive position sense and passive ankle stiffness. Those in the functional ankle instability group with higher passive ankle stiffness had smaller motion perception thresholds than those with lower passive ankle stiffness. Conclusion Unlike motion perception threshold, passive position sense is not affected by the presence of functional ankle instability. Passive ankle stiffness appears to influence proprioceptive acuity in persons with functional ankle instability. J Orthop Sports Phys Ther 2017;47(12):899-905. Epub 7 Oct 2017. doi:10.2519/jospt.2017.7030. PMID- 28990441 TI - Beware of predatory journals. PMID- 28990442 TI - Low-Income Senior Housing Residents' Emergency Department Use and Care Transition Problems. AB - Older adults may be at risk of adverse outcomes after emergency department (ED) visits due to ineffective transitions of care. Semi-structured interviews were employed to identify and categorize reasons for ED use and problems that occur during transition from the ED back to home among 14 residents of low-income senior housing. Qualitative thematic and descriptive analyses were used. Ambulance use, timely ED use or a wait-and-see approach, and lack of health-care provider contact before ED visit were emergent themes. Delayed medication receipt, no current medication list, and medication knowledge gaps were identified. Lack of a personal health record, follow-up care instruction, and worsening symptoms education emerged as transition problems from ED to home. After an ED visit, education opportunities exist around seeing primary care providers for nonurgent conditions, follow-up care, medications, and worsening condition symptoms. Timely receipt of discharge medications and medication education may improve medication-related transition problems. PMID- 28990443 TI - Mapping Quantitative Trait Loci Underlying Circadian Light Sensitivity in Drosophila. AB - Despite the significant advance in our understanding of the molecular basis of light entrainment of the circadian clock in Drosophila, the underlying genetic architecture is still largely unknown. The aim of this study was to identify loci associated with variation in circadian photosensitivity, which are important for the evolution of this trait. We have used complementary approaches that combined quantitative trait loci (QTL) mapping, complementation testing, and transcriptome profiling to dissect this variation. We identified a major QTL on chromosome 2, which was subsequently fine mapped using deficiency complementation mapping into 2 smaller regions spanning 139 genes, some of which are known to be involved in functions that have been previously implicated in light entrainment. Two genes implicated with the clock and located within that interval, timeless and cycle, failed to complement the QTL, indicating that alleles of these genes contribute to the variation in light response. Specifically, we find that the timeless s/ ls polymorphism that has been previously shown to constitute a latitudinal cline in Europe is also segregating in our recombinant inbred lines and is contributing to the phenotypic variation in light sensitivity. We also profiled gene expression in 2 recombinant inbred strains that differ significantly in their photosensitivity and identified a total of 368 transcripts that showed differential expression (false discovery rate < 0.1). Of 131 transcripts that showed a significant recombinant inbred line by treatment interaction (i.e., putative expression QTL), 4 are located within QTL2. PMID- 28990444 TI - Progress in the Full-Text Publication Rate of Orthopaedic and Sport Physical Therapy Abstracts Presented at the American Physical Therapy Association's Combined Sections Meeting. AB - Study Design Descriptive study. Background Professional meetings, such as the American Physical Therapy Association's (APTA's) Combined Sections Meeting (CSM), provide forums for sharing information. However, it was reported that only one quarter of orthopaedic and sports physical therapy abstracts presented at the CSM between 2000 and 2004 went on to full-text publication. This low conversion rate raises a number of concerns regarding the full dissemination of work within the profession. Objectives The purpose of this study was to determine the full-text publication rate of work presented in abstract form at subsequent CSMs and investigate factors influencing the rate. Methods A systematic search was undertaken to locate full-text publications of orthopaedic and sports physical therapy abstracts presented at CSMs between 2005 and 2011. Eligible publications were published within 5 years following abstract presentation. The influences of year of abstract presentation, APTA section, presentation type, institution of origin, study design, and study significance were assessed. Results Over one third (38.6%) of presented abstracts progressed to full-text publication. Odds of full-text publication increased if the abstract was presented as a platform presentation, originated from a doctorate-granting institution, reported findings of an experimental study, or reported a statistically significant finding. Conclusion The full-text publication rate for orthopaedic and sports physical therapy abstracts presented at recent CSMs has increased by over 50% compared to that reported for the preceding period. The rate is now in the range of that reported in comparable clinical disciplines, demonstrating important progress in the full dissemination of work within the profession. J Orthop Sports Phys Ther, Epub 7 Oct 2017. doi:10.2519/jospt.2018.7581. PMID- 28990445 TI - A non-linear relationship between the cumulative exposure to occupational stressors and nurses' burnout and the potentially emotion regulation factors. AB - BACKGROUND: Stressful situations can increase the likelihood of nurses experiencing negative emotions, especially burnout. AIMS: To explore the association of cumulative exposure to occupational stressors and emotion regulation strategies with nurses' burnout. METHODS: Participants were 602 nurses from three general hospitals in Jinan, China. Social demographic characteristics, occupational stress, burnout, and emotion regulation strategies (cognitive reappraisal, expressive suppression, and rumination), were assessed. RESULTS: Nearly 70% of nurses reported that they were burnt out. Those with a moderate level and high level of stressors were 3.203 times and 26.444 times more likely to have burnout, respectively (x2trend = 62.732). Logistic regression revealed that nurses had higher cognitive reappraisal score (odds ratios (OR) = 0.941), scored lower for burnout. Those who had higher expressive suppression score (OR = 1.054), higher rumination score (OR = 1.037), and a higher level of stressors (OR = 2.779-18.259) scored higher for burnout. The results of sensitivity analysis were similar. CONCLUSIONS: A non-linear relationship exists between the cumulative exposure to occupational stressors and nurses' burnout. Those who less frequently use cognitive reappraisal, more frequently use rumination and expressive suppression, and have a high level of stressors may be more likely to experience burnout. PMID- 28990446 TI - What is 'moral distress'? A narrative synthesis of the literature. AB - AIMS: The aim of this narrative synthesis was to explore the necessary and sufficient conditions required to define moral distress. BACKGROUND: Moral distress is said to occur when one has made a moral judgement but is unable to act upon it. However, problems with this narrow conception have led to multiple redefinitions in the empirical and conceptual literature. As a consequence, much of the research exploring moral distress has lacked conceptual clarity, complicating attempts to study the phenomenon. DESIGN: Systematic literature review and narrative synthesis (November 2015-March 2016). DATA SOURCES: Ovid MEDLINE(r) In-Process & Other Non-Indexed Citations 1946-Present, PsycINFO(r) 1967-Present, CINAHL(r) Plus 1937-Present, EMBASE 1974-24 February 2016, British Nursing Index 1994-Present, Social Care Online, Social Policy and Practice Database (1890-Present), ERIC (EBSCO) 1966-Present and Education Abstracts. REVIEW METHODS: Literature relating to moral distress was systematically retrieved and subjected to relevance assessment. Narrative synthesis was the overarching framework that guided quality assessment, data analysis and synthesis. RESULTS: In all, 152 papers underwent initial data extraction and 34 were chosen for inclusion in the narrative synthesis based on both quality and relevance. Analysis revealed different proposed conditions for the occurrence of moral distress: moral judgement, psychological and physical effects, moral dilemmas, moral uncertainty, external and internal constraints and threats to moral integrity. CONCLUSION: We suggest the combination of (1) the experience of a moral event, (2) the experience of 'psychological distress' and (3) a direct causal relation between (1) and (2) together are necessary and sufficient conditions for moral distress. PMID- 28990447 TI - Psychotic-like experiences in help-seeking adolescents: Dimensional exploration and association with different forms of bullying victimization - A developmental social psychiatry perspective. AB - BACKGROUND: Psychotic-like experiences (PLEs) are common in the general population and increase the risk of psychotic disorders. Adolescents are a high risk group of this condition. Stressful events, such as bullying, have a role in the onset of PLEs. This study has several aims: (1) to assess PLEs in adolescents seeking help from a Child and Adolescent Mental Health Service, (2) to assess the association of PLEs with specific bullying victimization and (3) to assess difference in PLEs and victimizations by sex and age. METHODS: Participants were help-seeking (HS) adolescents initially screened for PLEs. They completed an assessment including characteristics of PLEs and bullying victimization. We paid particular attention to different kinds of PLEs and victimization. RESULTS: In total, 50 PLE-positive adolescents screened from 324 HS adolescents (15.4%) constituted the sample. Paranoia and verbal bullying were the PLEs and form of victimization most represented, respectively. Verbal bullying was strongly associated with paranoia (odds ratio (OR): 4.40, confidence interval (CI): 2.8 5.9, p < .001). Results remained significant after controlling for confounder (socio-demographic, anxiety, depression and for the latter analysis also other forms of victimization). Furthermore, social manipulation showed a strong association of paranoia and physical bullying with grandiosity. Verbal bullying was also associated with psychotic negative symptoms, but controlling for emotional symptoms and other victimization led to a reduction in the effect. Men were more involved in physical victimization and experienced grandiosity; on the contrary, late adolescents were most involved in social victimization and negative psychotic symptoms Conclusion: PLEs are relevant in HS adolescents. Bullying victimization interacts with the onset of these phenomena. In particular, verbal bullying predicted paranoia onset significantly. PMID- 28990448 TI - Evaluation of hemostatic effect of polyelectrolyte complex-based dressings. AB - The aim of this work was to develop a polyelectrolyte complex-based hemostatic dressing made from chitosan and polygalacturonic acid. Porous dressings were fabricated by ultrasonication of chitosan and alginate solutions followed by freeze-drying. Since chitosan has inherent hemostatic properties, and polygalacturonic acid is anti-inflammatory in nature, it was desired to combine these two polymers to develop an effective hemostatic dressing, which may also promote wound healing. Porous structure of the bandages was observed using field emission scanning electron microscope. Blood clotting behavior was studied using whole blood clotting assay. Plasma recalcification time, prothrombin time, and activated partial thromboplastin time were also determined to study the mechanism of clotting. The dressings were found to accelerate clotting rates and showed increased thrombin activity with an increase in chitosan concentration. PMID- 28990449 TI - A Systematic Review and Meta-analysis of Childhood Health Utilities. AB - BACKGROUND: A common feature of most reviews or catalogues of health utilities has been their focus on adult health states or derivation of values from adult populations. More generally, utility measurement in or on behalf of children has been constrained by several methodological concerns. The objective of this study was to conduct the first comprehensive systematic review and meta-analysis of primary utility data for childhood conditions and descriptors, and to determine the effects of methodological factors on childhood utilities. METHODS: The review followed PRISMA guidelines. PubMed, Embase, Web of Science, PsycINFO, EconLit, CINAHL and Cochrane Library were searched for primary studies reporting health utilities for childhood conditions or descriptors using direct or indirect valuation methods. The Paediatric Economic Database Evaluation (PEDE) Porject was also searched for cost-utility analyses with primary utility values. Mean or median utilities for each of the main samples were catalogued, and weighted averages of utilities for each health condition were estimated, by valuation method. Mixed-effects meta-regression using hierarchical linear modeling was conducted for the most common valuation methods to estimate the utility decrement for each health condition category relative to general childhood population health, as well as the independent effects of methodological factors. RESULTS: The literature searches resulted in 272 eligible studies. These yielded 3,414 utilities when all sub-groups were considered, covering all ICD-10 chapters relevant to childhood health, 19 valuation methods, 12 respondent types, 8 modes of administration, and data from 36 countries. A total of 1,191 utility values were obtained when only main study samples were considered, and these were catalogued by health condition or descriptor, and methodological characteristics. 1,073 mean utilities for main samples were used for fixed-effects meta-analysis by health condition and valuation method. Mixed-effects meta-regressions estimated that 53 of 76 ICD-10 delineated health conditions, valued using the HUI3, were associated with statistically significant utility decrements relative to general population health, whereas 38 of 57 valued using a visual analog scale (VAS) were associated with statistically significant VAS decrements. For both methods, parental proxy assessment was associated with overestimation of values, whereas adolescents reported lower values than children under 12 y. VAS responses were more heavily influenced by mode of administration than the HUI3. CONCLUSION: Utilities and their associated distributions, as well as the independent contributions of methodological factors, revealed by this systematic review and meta-analysis can inform future economic evaluations within the childhood context. PMID- 28990450 TI - Revisiting the role of durable polymers in cardiovascular devices. AB - INTRODUCTION: Polymers are an essential component of drug-eluting stents (DES) used to control drug release but remain the most controversial component of DES technology. There are two types of polymers employed in DES: durable polymer based DES (DP-DES) and biodegradable polymer DES (BP-DES). First-generation DES were exclusively composed of DP and demonstrated increased rates of late stent failure due in part to poor polymer biocompatibility. Newer generations DES use more biocompatible durable polymers or biodegradable polymers. Areas covered: We will cover issues identified with 1st-generation DP-DES, areas of success and failure in 2nd-generation DP-DES and examine the promise and shortcomings of BP DES. Briefly, fluorinated polymers used in 2nd-generation DP-DES have excellent anti-thrombogenicity and better biocompatibility than 1st-generation DES polymers. However, these devices lead to persistent drug exposure to the endothelium which impairs endothelial function and predisposes towards neoatherosclerosis. Meanwhile, BP-DES has shortened the duration of drug exposure which might be beneficial for endothelial functional recovery leading to less neoatherosclerosis. However, it remains uncertain whether the long-term biocompatibility of bare metal surfaces is better than that of polymer-coated metals. Expert commentary: Each technology has distinct advantages, which can be optimized depending upon the particular characteristics of the patient being treated. PMID- 28990451 TI - Urine and oral fluid drug testing in support of pain management. AB - In recent years, the abuse of opioid drugs has resulted in greater prevalence of addiction, overdose, and deaths attributable to opioid abuse. The epidemic of opioid abuse has prompted professional and government agencies to issue practice guidelines for prescribing opioids to manage chronic pain. An important tool available to providers is the drug test for use in the initial assessment of patients for possible opioid therapy, subsequent monitoring of compliance, and documentation of suspected aberrant drug behaviors. This review discusses the issues that most affect the clinical utility of drug testing in chronic pain management with opioid therapy. It focuses on the two most commonly used specimen matrices in drug testing: urine and oral fluid. The advantages and disadvantages of urine and oral fluid in the entire testing process, from specimen collection and analytical methodologies to result interpretation are reviewed. The analytical sensitivity and specificity limitations of immunoassays used for testing are examined in detail to draw attention to how these shortcomings can affect result interpretation and influence clinical decision-making in pain management. The need for specific identification and quantitative measurement of the drugs and metabolites present to investigate suspected aberrant drug behavior or unexpected positive results is analyzed. Also presented are recent developments in optimization of test menus and testing strategies, such as the modification of the standard screen and reflexed-confirmation testing model by eliminating some of the initial immunoassay-based tests and proceeding directly to definitive testing by mass spectrometry assays. PMID- 28990452 TI - Do Medicare Beneficiaries Living With HIV/AIDS Choose Prescription Drug Plans That Minimize Their Total Spending? AB - This article examines whether California Medicare beneficiaries with HIV/AIDS choose Part D prescription drug plans that minimize their expenses. Among beneficiaries without low-income supplementation, we estimate the excess cost, and the insurance policy and beneficiary characteristics responsible, when the lowest cost plan is not chosen. We use a cost calculator developed for this study, and 2010 drug use data on 1453 California Medicare beneficiaries with HIV who were taking antiretroviral medications. Excess spending is defined as the difference between projected total spending (premium and cost sharing) for the beneficiary's current drug regimen in own plan vs spending for the lowest cost alternative plan. Regression analyses related this excess spending to individual and plan characteristics. We find that beneficiaries pay more for Medicare Part D plans with gap coverage and no deductible. Higher premiums for more extensive coverage exceeded savings in deductible and copayment/coinsurance costs. We conclude that many beneficiaries pay for plan features whose costs exceed their benefits. PMID- 28990453 TI - Deficiencies of Magnesium Replacement in the Critically Ill. PMID- 28990455 TI - Remote consulting with telemonitoring of continuous positive airway pressure usage data for the routine review of people with obstructive sleep apnoea hypopnoea syndrome: A systematic review. AB - Introduction Telehealth has the potential to offer more convenient care and reduce travel. We aimed to systematically review studies that assessed the effectiveness of teleconsultation plus telemonitoring in the review of people with obstructive sleep apnoea hypopnoea syndrome receiving continuous positive airway pressure therapy versus face-to-face care. Methods Following Cochrane methodology, we searched 10 electronic databases (November 2015), trial registries, and reference lists of included studies, for trials testing interventions that combined remote consultations with telemonitoring of usage/continuous positive airway pressure data. Outcomes measures were: proportion reviewed, continuous positive airway pressure adherence, symptom control, and satisfaction/acceptability and cost effectiveness. Results From 362 potentially relevant papers, we identified five randomised controlled trials ( n = 269 patients): four from North America and one from Spain. Risk of bias was moderate in one, and moderate/high in four trials. Two trials reported number/duration of reviews with inconsistent results. The teleconsultation/telemonitoring improved continuous positive airway pressure adherence in two trials ( n = 19; n = 75); two ( n = 114 and n = 75) reported no between-groups differences. Two studies, both at moderate/high risk of bias, showed no between-group difference in the Epworth Sleepiness Score. Satisfaction was generally reported positively in all five trials; one trial reported that the teleconsultation/telemonitoring patients were 'more likely to continue' with continuous positive airway pressure therapy treatment. One study reported teleconsultation/telemonitoring as cost effective. Discussion The evidence for teleconsultation/telemonitoring in continuous positive airway pressure users is limited; however, no safety concerns have been raised. Adequately powered, well designed trials are needed to establish whether real-time telemonitoring and remote teleconsultation is a clinically and cost effective option for people using continuous positive airway pressure therapy. PMID- 28990454 TI - Perceived risks and use of psychotherapy via telemedicine for patients at risk for suicide. AB - Introduction Suicide is a major public health problem and its human, emotional, and economic costs are significant. Individuals in rural areas are at highest risk for suicide. However, telemedicine services are typically not rendered to individuals who are actively suicidal. The goals of the current study were to identify the risks of using telemedicine for mental healthcare from the perspective of licensed mental health providers and to determine factors associated with the use of telemedicine with patients who are at high risk for suicide. Methods A total of 52 licensed mental health providers were recruited online through several professional organization listservs and targeted emails. Providers completed online questionnaires regarding demographics, caseload of suicidal patients, perceived risks for using telemedicine with patients at risk for suicide, attitudes towards telemedicine, and use of telemedicine with patients at risk for suicide. Results Three key perceived risks associated with using telemedicine were identified, including assessment, lack of control over patient, and difficulties triaging patients if needed. It was also found that individuals who had more positive attitudes towards telemedicine, younger providers, and more experienced providers were more likely to use telemedicine with patients who are at high risk for suicide. Discussion To our knowledge, this is the first study to examine the perceived risks and use of telemedicine with patients at high risk for suicide. It is essential to continue this line of research to develop protocols for the provision of evidence-based therapy via telemedicine for this high-risk group. PMID- 28990456 TI - Cerebrospinal fluid spaces between intracranial venous sinuses and overlying dura mater: magnetic resonance imaging. AB - Purpose The intracranial venous sinuses are thought to lie interdurally, circumferentially contacting the dura maters. There has been no report documenting the cerebrospinal fluid spaces intervening between the venous sinuses and overlying dura mater. Here, we explored such structures using magnetic resonance imaging. Methods A total of 206 patients underwent magnetic resonance imaging with a T2-weighted or constructive interference steady-state sequence. Imaging data were analysed on a workstation. Results The peri-superior sagittal sinus cerebrospinal fluid spaces were identified in 100% of 133 patients who underwent coronal and sagittal T2-weighted imaging and in 98.6% of 73 with a constructive interference steady-state sequence. Among the 205 patients, the cerebrospinal fluid spaces were distributed over the frontoparietal region in 84% and the parietal region in 16%. On sagittal sections performed for 58 patients, the cerebrospinal fluid spaces were identified between the superior sagittal sinus and overlying dura mater. The peri-sinus spaces were found in 91% of the identified transverse sinuses, 29% of the straight and 70% of the occipital sinuses. The peri-superior sagittal sinus cerebrospinal fluid spaces were classified into five distinct appearances. The circumferential type was the most predominant and was found in 68.7%, followed by lateral in 10.2%, lateral plus inferior in 7.5%, lateral plus superior in 6.8% and superior in 6.8%. Conclusions The intracranial venous sinuses do not circumferentially contact with the dura maters. Instead, they are adjacent to the cerebrospinal fluid spaces intervening between the walls and overlying dura maters. These spaces are critical when considering tumour extensions contralateral to the superior sagittal sinus and safe surgical manoeuvres around it. PMID- 28990458 TI - Corrigendum to 'Ultraviolet-A1 irradiation therapy for systemic lupus erythematosus'. PMID- 28990459 TI - Multi-objective performance investigation of orthopaedic bone drilling using Taguchi membership function. AB - Orthopaedic bone drilling attacks the surrounded bone cells and tissues in terms of thermal and mechanical in such a way that these cells can get damaged permanently. This damage to the surrounding of drill point upsurges the rehabilitation time of injury and in some cases leads to the failure of the bone screw joint. This study is based on the optimization of multiple response characteristics to minimize the damage during the bone drilling. All real-life problems, including bone drilling, require the multiple response optimization for getting a combined optimization result for all countable response characteristics. The Taguchi optimization technique is observed as a highly recommended tool for single response optimization. This article uses the Taguchi technique with little modification of membership function that will help to convert the multiple response characteristics into single response and further optimize it as a single function of performance. Rotational speed, feed rate of tool at three different levels with three different kinds of drilling tools are the drilling parameters selected for the study. The objective of this study is to minimize the surface roughness and thrust force simultaneously. Analysis of variance helps to find the percentage contribution and significance of each parameter on the performance. PMID- 28990457 TI - Age at First Exposure to Repetitive Head Impacts Is Associated with Smaller Thalamic Volumes in Former Professional American Football Players. AB - Thalamic atrophy has been associated with exposure to repetitive head impacts (RHI) in professional fighters. The aim of this study is to investigate whether or not age at first exposure (AFE) to RHI is associated with thalamic volume in symptomatic former National Football League (NFL) players at risk for chronic traumatic encephalopathy (CTE). Eighty-six symptomatic former NFL players (mean age = 54.9 +/- 7.9 years) were included. T1-weighted data were acquired on a 3T magnetic resonance imager, and thalamic volumes were derived using FreeSurfer. Mood and behavior, psychomotor speed, and visual and verbal memory were assessed. The association between thalamic volume and AFE to playing football and to number of years playing was calculated. Decreased thalamic volume was associated with more years of play (left: p = 0.03; right: p = 0.03). Younger AFE was associated with decreased right thalamic volume (p = 0.014). This association remained significant after adjusting for total years of play. Decreased left thalamic volume was associated with worse visual memory (p = 0.014), whereas increased right thalamic volume was associated with fewer mood and behavior symptoms (p = 0.003). In our sample of symptomatic former NFL players at risk for CTE, total years of play and AFE were associated with decreased thalamic volume. The effect of AFE on right thalamic volume was almost twice as strong as the effect of total years of play. Our findings confirm previous reports of an association between thalamic volume and exposure to RHI. They suggest further that younger AFE may result in smaller thalamic volume later in life. PMID- 28990460 TI - Amplification of specific chromosomal regions assessed by fluorescent in situ hybridization on Pap smears to be added as screening tool for identifying women at risk of progressing to cervical cancer. AB - Cervical carcinoma is a frequent malignancy in developing countries despite being a preventable disease. For the first time, four screening tests were used simultaneously for identifying women with a risk of developing cervical cancer, to help clinicians and policy makers to implement the best strategy for reducing the burden of this disease. Women visiting a hospital in India were enrolled after institutional ethics clearance and informed consent. Visual inspection using acetic acid and Pap smear tests were performed on 2683 women, and 104 had abnormal cytology: atypical squamous cells of undetermined significance (n = 29), low-grade squamous intraepithelial lesion (n = 41), high-grade squamous intraepithelial lesion (n = 17), and squamous cell carcinoma (n = 17). These and 96 samples, with normal cytology, were subjected to high-risk human papilloma virus testing and fluorescent in situ hybridization evaluation. Women with abnormal cytology were followed for 5 years and evaluated with colposcopy-guided biopsy. Three accepted methods of screening and one novel fluorescent in situ hybridization assay were carried out in 200 cases. Cutoffs for fluorescent in situ hybridization were established. The screening methods had 88%-96% negative predictive value, while positive predictive value was low (20%) for visual inspection using acetic acid, 47% for fluorescent in situ hybridization, 56% for high-risk human papilloma virus, and 73% for combined high-risk human papilloma virus and fluorescent in situ hybridization. Combined high-risk human papilloma virus and fluorescent in situ hybridization had 94% sensitivity, specificity, and negative predictive value, suggesting that simultaneous screening with these two tests is appropriate for identifying women progressing to cervical cancer and not visual inspection using acetic acid, which has low positive predictive value and Pap cytology which requires to be repeated. Policy makers and clinicians can assess feasibility of incorporating this screening strategy to prevent cervical cancer. PMID- 28990461 TI - Enrichment of Helicobacter pylori mutant strains after eradication therapy analyzed by gastric wash-based quantitative pyrosequencing. AB - The eradication of Helicobacter pylori reduces the risk of gastric cancer. A clear understanding of the factors underlying mixed infection with multiple clarithromycin-susceptible and clarithromycin-resistant H. pylori strains is necessary to design more effective therapies against H. pylori. We aimed to assess how the abundance and prevalence of H. pylori strains vary after clarithromycin-based eradication therapy. Using gastric wash samples, which represent the entire stomach, we sequentially analyzed the abundance and prevalence of H. pylori DNA by 23S ribosomal RNA pyrosequencing before and 1, 2, and 3 years after eradication therapy. Low levels of H. pylori DNA were still detectable at the first-year follow-up in all samples with negative post treatment urea breath test results. The abundance of H. pylori DNA decreased significantly until the 2-year follow-up, but it switched to an increase at the 3 year follow-up. Importantly, the ratio of the prevalence of mutant strains to the prevalence of wild-type strains had already increased at the first-year follow-up and continued to increase, suggesting the selection and growth of clarithromycin resistant strains during the follow-up periods. Being sensitive and representative, our assay will be useful in effectively addressing gastric cancer development by enhancing the long-term success of intervention strategies and consecutive surveillance for H. pylori eradication. PMID- 28990462 TI - Advanced Therapy Medicinal Products: A Guide for Bone Marrow-derived MSC Application in Bone and Cartilage Tissue Engineering. AB - Millions of people worldwide suffer from trauma- or age-related orthopedic diseases such as osteoarthritis, osteoporosis, or cancer. Tissue Engineering (TE) and Regenerative Medicine are multidisciplinary fields focusing on the development of artificial organs, biomimetic engineered tissues, and cells to restore or maintain tissue and organ function. While allogenic and future autologous transplantations are nowadays the gold standards for both cartilage and bone defect repair, they are both subject to important limitations such as availability of healthy tissue, donor site morbidity, and graft rejection. Tissue engineered bone and cartilage products represent a promising and alternative approach with the potential to overcome these limitations. Since the development of Advanced Therapy Medicinal Products (ATMPs) such as TE products requires the knowledge of diverse regulation and an extensive communication with the national/international authorities, the aim of this review is therefore to summarize the state of the art on the clinical applications of human bone marrow derived stromal cells for cartilage and bone TE. In addition, this review provides an overview of the European legislation to facilitate the development and commercialization of new ATMPs. PMID- 28990463 TI - Are People Becoming More Entitled Over Time? Not in New Zealand. AB - It is a common conception that entitlement is increasing among younger generations over time. However, although there is some evidence for this trend, other findings are less conclusive. The current research investigated change in psychological entitlement across the adult lifespan for men and women (ages 19 74), using six annual waves of data (2009-2014) from the New Zealand Attitudes and Values Study ( N = 10,412). We employed Cohort-Sequential Latent Growth Modeling to assess mean-level change in entitlement. Entitlement was found to be generally unchanging over time for both men and women, with only those aged 65 and above showing increasing entitlement. Entitlement showed a steady downward trend across age. These findings from a large national probability sample suggest that change in entitlement may follow a decreasing developmental trend across the lifespan. In New Zealand, at least, there is no evidence for a narcissism epidemic. PMID- 28990464 TI - The opinions of ambulance personnel regarding using a heated mattress for patients being cared for in a cold climate - An intervention study in ambulance care. AB - The purpose of the study was to describe the opinions of ambulance personnel regarding differences between using a heated mattress and a standard ambulance mattress. This study was an intervention study with pre- and post-evaluation. Evaluations of the opinions of personnel regarding the standard unheated mattress were conducted initially. After the intervention with new heated mattresses, follow-up evaluations were conducted. Ambulance personnel (n=64) from an ambulance station in northern Sweden took part in the study, which ran from October 2014 until February 2016. There were differences in opinions regarding the standard unheated mattress and the new heated mattress. The evaluation of the proxy ratings by the personnel showed that the heated mattress was warmer than the standard mattress, more pleasant to lie on and that patients were happier and more relaxed than when the standard mattress was used. The ambulance personnel in this study rated the experience of working with the heated mattress as very positive and proxy rated that it had a good effect on patient comfort. A heated mattress can be recommended for patients in ambulance care, even if more research is needed to receive sufficient evidence. PMID- 28990465 TI - Statins induce apoptosis through inhibition of Ras signaling pathways and enhancement of Bim and p27 expression in human hematopoietic tumor cells. AB - Recently, statins have been demonstrated to improve cancer-related mortality or prognosis in patients of various cancers. However, the details of the apoptosis inducing mechanisms remain unknown. This study showed that the induction of apoptosis by statins in hematopoietic tumor cells is mediated by mitochondrial apoptotic signaling pathways, which are activated by the suppression of mevalonate or geranylgeranyl pyrophosphate biosynthesis. In addition, statins decreased the levels of phosphorylated extracellular signal-regulated kinase 1/2 and mammalian target of rapamycin through suppressing Ras prenylation. Furthermore, inhibition of extracellular signal-regulated kinase 1/2 and mammalian target of rapamycin by statins induced Bim expression via inhibition of Bim phosphorylation and ubiquitination and cell-cycle arrest at G1 phase via enhancement of p27 expression. Moreover, combined treatment of U0126, a mitogen activated protein kinase kinase 1/2 inhibitor, and rapamycin, a mammalian target of rapamycin inhibitor, induced Bim and p27 expressions. The present results suggested that statins induce apoptosis by decreasing the mitochondrial transmembrane potential, increasing the activation of caspase-9 and caspase-3, enhancing Bim expression, and inducing cell-cycle arrest at G1 phase through inhibition of Ras/extracellular signal-regulated kinase and Ras/mammalian target of rapamycin pathways. Therefore, our findings support the use of statins as potential anticancer agents or concomitant drugs of adjuvant therapy. PMID- 28990466 TI - Task-dependent cold stress during expeditions in Antarctic environments. AB - This study seeks to understand the degree of body cooling, cold perception and physical discomfort during Antarctic tour excursions. Eight experienced expedition leaders across three Antarctic cruise voyages were monitored during occupational tasks: kayaking, snorkelling and zodiac outings. Subjective cold perception and discomfort were recorded using a thermal comfort assessment and skin temperature was recorded using a portable data logger. Indoor cabin temperature and outdoor temperature with wind velocity were used as measures of environmental stress. Physical activity level and clothing insulation were estimated using previous literature. Tour leaders experienced a 6 degrees C (2 degrees C wind chill) environment for an average of 6 hours each day. Leaders involved in kayaking reported feeling colder and more uncomfortable than other leaders, but zodiac leaders showed greater skin temperature cooling. Occupational experience did not predict body cooling or cold stress perception. These findings indicate that occupational cold stress varies by activity and measurement methodology. The current study effectively used objective and subjective measures of cold-stress to identify factors which can contribute to risk in the Antarctic tourism industry. Results suggest that the type of activity may moderate risk of hypothermia, but not discomfort, potentially putting individuals at risk for cognitive related mistakes and cold injuries. PMID- 28990467 TI - Mobility Analysis of AmpuTees (MAAT I): Quality of life and satisfaction are strongly related to mobility for patients with a lower limb prosthesis. AB - BACKGROUND: While rehabilitation professionals are historically trained to place emphasis on the restoration of mobility following lower limb amputation, changes in healthcare dynamics are placing an increased emphasis on the limb loss patient's quality of life and general satisfaction. Thus, the relationship between these constructs and mobility in the patient with lower limb loss warrants further investigation. OBJECTIVES: To determine the relationship between mobility of the patient with lower limb loss and both (1) general satisfaction and (2) quality of life. STUDY DESIGN: Retrospective chart analysis. METHODS: A retrospective chart review of the Prosthetic Limb Users Survey of Mobility and the Prosthesis Evaluation Questionnaire-Well-Being subsection. Pearson correlations were used to test relationships. RESULTS: Data from 509 patients with a lower limb prosthesis were included. Mobility was found to be positively correlated with quality of life ( r = 0.511, p < 0.001, 95% confidence interval (0.443, 0.569)) and general satisfaction ( r = 0.475, p < 0.001, 95% confidence interval (0.403, 0.542)), as well as their arithmetic mean (i.e. Prosthesis Evaluation Questionnaire-Well-Being) ( r = 0.533, p < 0.001, 95% confidence interval (0.466, 0.592)). CONCLUSION: This study provides evidence of a strong positive correlation between mobility and both quality of life and general satisfaction. Thus, in the holistic care of a patient with lower limb loss, maximizing mobility would correlate with greater quality of life and general satisfaction. Clinical relevance There is growing emphasis on the quality of life and general satisfaction experienced by patients undergoing prosthetic rehabilitation. The results of this study underscore the importance of providing prosthetic rehabilitation that maximizes the patient's mobility, noting that these individuals also report greater quality of life and general satisfaction. PMID- 28990468 TI - Deep-Sea Phylogeographic Structure Shaped by Paleoenvironmental Changes and Ongoing Ocean Currents Around the Sea of Japan in a Crangonid Shrimp, Argis lar. AB - The deep-sea crangonid shrimp, Argis lar, is a highly abundant species from the northern Pacific Ocean. We investigated its phylogeographic and demographic structure across the species' extensive range, using mitochondrial DNA sequence variation to evaluate the impact of deep-sea paleoenvironmental dynamics in the Sea of Japan on population histories. The haplotype network detected three distinct lineages with allopatric isolation, which roughly corresponded to the Sea of Japan (Lineage A), the northwestern Pacific off the Japanese Archipelago (Lineage B), and the Bering Sea/Gulf of Alaska (Lineage C). Lineage A showed relatively low haplotype and nucleotide diversity, a significantly negative value of Tajima's D, and a star-shaped network, suggesting that anoxic bottom-water in the Sea of Japan over the last glacial period may have brought about a reduction in the Sea of Japan population. Furthermore, unexpectedly, the distributions of Lineage A and B were closely related to the pathways of the two ocean currents, especially along the Sanriku Coast. This result indicated that A. lar could disperse across shallow straits through the ocean current, despite their deep-sea adult habitat. Bayesian inference of divergence time revealed that A. lar separated into three lineages approximately 1 million years before present (BP) in the Pleistocene, and then had been influenced by deep-sea paleoenvironmental change in the Sea of Japan during the last glacial period, followed by a more recent larval dispersal with the ocean current since ca. 6 kilo years BP. PMID- 28990469 TI - Identification and Characterization of Novel Genes Expressed Preferentially in the Corpora Allata or Corpora Cardiaca During the Juvenile Hormone Synthetic Period in the Silkworm, Bombyx mori. AB - Juvenile hormone (JH) plays important roles in insect development and physiology. JH titer is tightly regulated to coordinately adjust systemic physiology and development. Although control of JH titer is explained by the expression of JH biosynthetic enzymes in the corpora allata (CA), molecular mechanisms that regulate the expression of these genes remain elusive. In the present study, to identify novel regulators of JH biosynthetic genes, we conducted a gene expression screen using the CA and corpora cardiaca (CC) of the silkworm, Bombyx mori, in the JH synthesis period. We identified seven candidate genes and characterized their properties through extensive expression analyses. Of these candidates, we found that a novel gene, which encodes type II phosphatidylinositol 3,4-bisphosphate [PI(3,4)P2] 4-phosphatase, shows highly correlated expression with JH titer. In addition, expression of this gene was strongly upregulated by starvation, when JH biosynthetic enzyme genes are concurrently upregulated. These results, for the first time, imply possible involvement of phosphoinositol signal in regulation of JH biosynthesis, providing novel insights into molecular mechanisms of nutrition-dependent regulation of JH biosynthesis. PMID- 28990471 TI - Corrigenda. PMID- 28990470 TI - Reproductive Traits of the Duckbill Sleeper Butis butis (Hamilton, 1822). AB - Butis butis is a commercially important goby that is widely distributed in Indo Pacific regions; however, its reproductive biology is poorly characterized. We condcted the present study in estuarine and coastline areas in the Mekong Delta from June 2015 to May 2016 to generate reproductive parameters for this species. The results of data analysis based on a collection of 173 individuals (74 females and 99 males) indicate that the sex ratio of this species is close to 1:1. Mature (stage IV) and ripe (stage V) gonads were found monthly during the study period, suggesting that Butis butis is an iteroparous fish that spawns in a year-round cycle. Male B. butis matures first at 8.97 cm total length (TL), which is longer than females (6.82 cm TL). Butis butis is well adapted to tropical monsoon regions due to its high batch fecundity (46,017 +/- 6941 SE), ranging from 15,000 (8.6 cm TL and 5.71 g W) to 78,500 (15.8 cm TL and 42.24 g W) eggs. Batch fecundity increases with fish size due to a strong positive relationship between batch fecundity and fish size (TL and W). These results help fill the knowledge gap on the reproductive biology of Butis butis, and contribute crucial information relevant to sustainable management of fish populations in the study region. PMID- 28990472 TI - An Inhibitor of Thyroid Hormone Synthesis Protects Tail Skin Grafts Transplanted to Syngenic Adult Frogs. AB - Tail regression in amphibian tadpoles during metamorphosis is one of the most dynamic morphological changes in animal development and is induced by thyroid hormone (TH). It has been proposed that tail resorption is driven by immunological rejection in Xenopus laevis, based on experimental evidence showing that larval skin grafts become atrophic on syngenic recipient adult frogs. This led to the hypothesis that tail regression is induced by an immunological rejection against larval skin-specific antigens called Ouro proteins. However, our group has demonstrated that ouro-knockout tadpoles undergo normal metamorphosis, including tail resorption in Xenopus tropicalis, which indicates that the expression of ouro genes is not necessary for tail regression. In the present study, we showed that an inhibitor of TH synthesis promotes the survival of larval tail skin grafts on syngenic adult Xenopus tropicalis frogs. The levels of endogenous THs in adult frogs were also comparable to those in metamorphosing tadpoles of Xenopus laevis with a regressing tail, and TH induced the regression of tadpole tail tips of Xenopus tropicalis in organ culture. Taken together, these results strongly suggest that endogenous THs in the recipient adult frog induce the degeneration of syngenic tail skin grafts. PMID- 28990473 TI - Chick Development and Asynchroneous Hatching in the Zebra Finch (Taeniopygia guttata castanotis). AB - The mode of hatching in birds has important impacts on both parents and chicks, including the costs and risks of breeding for parents, and sibling competition in a clutch. Birds with multiple eggs in a single clutch often begin incubating when most eggs are laid, thereby reducing time of incubation, nursing burden, and sibling competition. In some songbirds and some other species, however, incubation starts immediately after the first egg is laid, and the chicks thus hatch asynchronously. This may result in differences in parental care and in sibling competition based on body size differences among older and younger chicks, which in turn might produce asynchronous development among siblings favoring the first hatchling, and further affect the development and fitness of the chicks after fledging. To determine whether such processes in fact occur in the zebra finch, we observed chick development in 18 clutches of zebra finches. We found that there were effects of asynchronous hatching, but these were smaller than expected and mostly not significant. Our observations suggest that the amount of care given to each chick may be equated with such factors as a camouflage effect of the down feathers, and that the low illumination within the nest also complicates the determination of the hatching order by the parents. PMID- 28990474 TI - Telomerase Reverse Transcriptase Gene from Greasyback Shrimp Metapenaeus ensis: Isolation, Genomic Organization and Expression Pattern Analysis. AB - Telomerase reverse transcriptase (TERT), a catalytic subunit of telomerase, plays a key role in the activity and biological functions of telomerase. In the present study we isolated and characterized the full-length cDNA and DNA sequences of the TERT gene (MeTERT) from Metapenaeus ensis. MeTERT cDNA was 4239 bp in length, which consisted of a 369 bp 5'UTR, a 3231 bp open reading frame encoding 1076 amino acids, and a 639 bp 3'UTR. The genomic DNA of MeTERT had only two introns, similar to beetle (two introns) and silkworm (intronless). The MeTERT protein showed only 5.2-7.9% identity with other known TERTs but contained all the four primary TERT domains of the N-terminal TEN, RNA binding domain (TRBD), reverse transcriptase (RT) and C-terminus CTE. Expression pattern analysis by RT-qPCR showed that, the MeTERT mRNA transcripts could be detected in all the tested samples, with relatively higher expression level in the gill, mysis, Oka organ and egg, but lower level in muscle, ovary, in vitro cultured 3-d Oka organ cells and heart. The significant decrease of MeTERT expression in the in vitro cultured 3-d Oka organ primary cells compared with their source tissue of Oka organ may have contributed to the cellular mitosisarrest. Thus trans-activation of TERT gene may be a candidate in attempts to immortalize in vitro cultured shrimp cells. This work will lay a solid foundation for future studies of the biological functions of telomerase in crustaceans. PMID- 28990475 TI - Histology of the Urogenital System in the American Bullfrog (Rana catesbeiana), with Emphasis on Male Reproductive Morphology. AB - Previous studies have revealed variations in the urogenital system morphology of amphibians. Recently, the urogenital system of salamanders was reviewed and terminology was synonymized across taxa. Discrepancies exist in the terminology describing the urogenital system of anurans, which prompted our group to develop a complete, detailed description of the urogenital system in an anuran species and provide nomenclature that is synonymous with those of other amphibian taxa. In Rana catesbeiana, sperm mature within spermatocysts of the seminiferous tubule epithelia and are transported to a series of intratesticular ducts that exit the testes and merge to form vasa efferentia. Vasa efferentia converge into single longitudinal ducts (Bidder's ducts) on the lateral aspects of the kidneys. Branches from the longitudinal ducts merge with genital kidney renal tubules through renal corpuscles. The nephrons travel caudally and empty into the Woffian ducts. Similar to salamanders, the caudal portion of the kidneys (termed the pelvic kidneys in salamanders) only possesses nephrons involved in urine formation, not sperm transport. Data from the present study provide a detailed description and synonymous nomenclature that can be used to make future comparative analyses between taxa more efficient. PMID- 28990476 TI - Disruption of the Reproductive Axis in Freshwater Fish, Catla catla, After Bisphenol-A Exposure. AB - Environmental estrogens such as bisphenol-A (BPA) cause reproductive disorders in many vertebrate species, especially fish. BPA is used extensively in the manufacture of plastic and plastic products, epoxy resins, and dental sealants. The presence of BPA in sewage and surface water raises a potential threat to aquatic populations. In the present study, we investigated the effects of BPA on ovarian histology and transcription of key genes involved in reproduction. Adult female Catla catla were exposed to graded concentrations of BPA (10, 100, 1000 ug/l) for 14 days. Ovary histology and expression of steroidogenic acute regulatory protein (star), ovary aromatase (cyp19a), follicle-stimulating hormone receptor (fshr), and luteinizing hormone receptor (lhr) were evaluated in ovary of female fish after 14 days. Fish ovaries from the control and 10 ug/l BPA exposed groups included primary oocytes (POCs), while fish exposed to higher concentrations of BPA (100 and 1000 ug/l) contained tertiary and mature oocytes with increased numbers of atretic follicles. Significant increases in mRNA transcripts of star were observed in fish exposed to 100 and 1000 ug/l BPA. A 15 fold increase in the expression of ovary aromatase (cyp19a) was detected in fish exposed to 100 ug/l BPA. fshr increased in a dose-dependent manner. Increases in the expression of lhr, although not statistically significant, were observed in fish exposed to 100 and 1000 ug/l BPA when compared to control. The results of the present study indicate that BPA causes alterations in the expression patterns of genes involved in the reproductive pathway, which may lead to negative effects on the reproductive system in female fish. PMID- 28990477 TI - External Asymmetry and Pectoral Fin Loss in the Bamboo Sole (Heteromycteris japonica): Small-Sized Sole with Potential as a Pleuronectiformes Experimental Model. AB - Pleuronectiform fish develop marked external asymmetry in eye location and skin color at metamorphosis. The bamboo sole, Heteromycteris japonica, also exhibits loss of the pectoral fins at metamorphosis. Because of its small body size, short generation time, and long spawning season, we focused on the bamboo sole as an experimental model to investigate metamorphic asymmetry and pectoral fin loss during development. In the present study, we utilized a small-scale culture system to evaluate bamboo sole larvae and larval development, and a microinjection system for fertilized eggs. The culture system described here uses an 18 L culture tank for rotifers (the first diet for larvae) and 5 L plastic beakers for larval culture. Under this system, most larvae completed metamorphosis, including one-eye migration and pigmentation of the ocular side, by 23 days postfertilization (dpf) at 25 degrees C. Larvae at density of 120-150 per liter were grown from hatching to 23 dpf with a survival ratio of 60-75% per beaker. Pectoral fins, including coracoid and disk cartilage, formed but were completely lost in late metamorphosis without formation of proximal radials and fin rays. The microinjection system designed here is adequate for the bamboo sole and allows injection of 100 one-cell-stage embryos per day. We expect that the culture and microinjection systems described here will facilitate the use of the bamboo sole as an experimental model organism in developmental biology. PMID- 28990478 TI - Changes in Plasma and Tissue Long-Chain Polyunsaturated Fatty Acid (LC-PUFA) Content in the Eel Anguilla japonica After External and Internal Osmotic Stress. AB - We investigated the effect of external and internal osmotic stress on the profile of long-chain polyunsaturated fatty acids (LC-PUFA) in euryhaline eels Anguilla japonica. Freshwater (FW) fish were transferred to seawater (SW) for external osmotic stress or subjected to internal stress through injection with hypertonic saline. FW eels injected with isotonic saline served as controls. Plasma osmolality, Na+ concentration, and gill Na+/K+ -ATPase activity increased, but hematocrit decreased compared with controls in eels exposed to external or internal osmotic stress. The expression of two major transporter genes for SW adaptation, the Na+ -K+ -2Cl - co-transporter 1a (NKCC1a) in the gill and NKCC2b in the intestine, was up-regulated only in SW-transferred eels, suggesting a direct impact of SW on the gill and intestine via SW ingestion. Total LC-PUFA contents and DHA (22:6 n-3) increased in the gill and liver of SW-transferred eels and in the intestine of hypertonic saline-injected eels. However, total LC PUFA content in plasma decreased after both external and internal osmotic stimuli. In contrast, the gene expression of two key enzymes involved in the LC PUFA biosynthesis, Delta6 fatty acid desaturase and elongase, did not change in the gill, intestine and liver of osmotically stressed eels. These results indicate that LC-PUFA is possibly involved in osmoregulation and the increased LC PUFA contents of osmoregulatory organs might be a result of LC-PUFA transport via circulation, rather than through de novo biosynthesis. PMID- 28990479 TI - Laboratory Rearing System for Ischnura senegalensis (Insecta: Odonata) Enables Detailed Description of Larval Development and Morphogenesis in Dragonfly. AB - In an attempt to establish an experimental dragonfly model, we developed a laboratory rearing system for the blue-tailed damselfly, Ischnura senegalensis. Adoption of multi-well plastic plates as rearing containers enabled mass-rearing of isolated larvae without cannibalism and convenient microscopic monitoring of individual larvae. Feeding Artemia brine shrimps to younger larvae and Tubifex worms for older larvae resulted in low mortality, synchronized ecdysis, and normal development of the larvae. We continuously monitored the development of 118 larvae every day, of which 49 individuals (41.5%) reached adulthood. The adult insects were fed with Drosophila flies in wet plastic cages, attained reproductive maturity in a week, copulated, laid fertilized eggs, and produced progeny. The final larval instar varied from 9th to 12th, with the 11th instar (56.5%) and the 12th instar (24.2%) constituting the majority. From the 1st instar to the penultimate instar, the duration of each instar was relatively short, mainly ranging from three to 11 days. Afterwards, the duration of each instar was prolonged, reaching 7-25 days for the penultimate instar and 14-28 days for the final instar. Some larvae of final, penultimate and younger instars were subjected to continuous and close morphological examinations, which enabled developmental staging of larvae based on size, shape, and angle of compound eyes and other morphological traits. This laboratory rearing system may facilitate the understanding of physiological, biochemical, and molecular mechanisms underlying metamorphosis, hormonal control, morphogenesis, body color polymorphism, and other biological features of dragonflies. PMID- 28990480 TI - Dyella-Like Bacterium Isolated from an Insect as a Potential Biocontrol Agent Against Grapevine Yellows. AB - Yellows diseases, caused by phytopathogenic bacteria of the genus Phytoplasma, are a major threat to grapevines worldwide. Because conventional applications against this pathogen are inefficient and disease management is highly challenging, the use of beneficial bacteria has been suggested as a biocontrol solution. A Dyella-like bacterium (DLB), isolated from the Israeli insect vector of grapevine yellows (Hyalesthes obsoletus), was suggested to be an endophyte. To test this hypothesis, the bacterium was introduced by spraying the plant leaves, and it had no apparent phytotoxicity to grapevine. Fluorescent in situ hybridization analysis showed that DLB is colonizing grapevine phloem. Because phytoplasmas inhabit the same niche, DLB interactions with this phytopathogen were examined. When the isolate was introduced to phytoplasma-infected Chardonnay plantlets, morphological disease symptoms were markedly reduced. The mode of DLB action was then tested using bioinformatics and system biology tools. DLB genome analysis suggested that the ability to reduce phytoplasma symptoms is related to inhibition of the pathogenic bacterium. These results provide the first step in examining the potential of DLB as a biological control agent against phytoplasmas in grapevine and, possibly, other agricultural crops. PMID- 28990481 TI - Challenges for Managing Candidatus Liberibacter spp. (Huanglongbing Disease Pathogen): Current Control Measures and Future Directions. AB - Huanglongbing (HLB; "citrus greening" disease) has caused significant damages to the global citrus industry as it has become well established in leading citrus producing regions and continues to spread worldwide. Insecticidal control has been a critical component of HLB disease management, as there is a direct relationship between vector control and Candidatus Liberibacter spp. (i.e., the HLB pathogen) titer in HLB-infected citrus trees. In recent years, there have been substantial efforts to develop practical strategies for specifically managing Ca. Liberibacter spp.; however, a literature review on the outcomes of such attempts is still lacking. This work summarizes the greenhouse and field studies that have documented the effects and implications of chemical-based treatments (i.e., applications of broad-spectrum antibiotics, small molecule compounds) and nonchemical measures (i.e., applications of plant-beneficial compounds, applications of inorganic fertilizers, biological control, thermotherapy) for phytopathogen control. The ongoing challenges associated with mitigating Ca. Liberibacter spp. populations at the field-scale, such as the seasonality of the phytopathogen and associated HLB disease symptoms, limitations for therapeutics to contact the phytopathogen in planta, adverse impacts of broad spectrum treatments on plant-beneficial microbiota, and potential implications on public and ecosystem health, are also discussed. PMID- 28990482 TI - Advanced Copper Composites Against Copper-Tolerant Xanthomonas perforans and Tomato Bacterial Spot. AB - Bacterial spot, caused by Xanthomonas spp., is a widespread and damaging bacterial disease of tomato (Solanum lycopersicum). For disease management, growers rely on copper bactericides, which are often ineffective due to the presence of copper-tolerant Xanthomonas strains. This study evaluated the antibacterial activity of the new copper composites core-shell copper (CS-Cu), multivalent copper (MV-Cu), and fixed quaternary ammonium copper (FQ-Cu) as potential alternatives to commercially available micron-sized copper bactericides for controlling copper-tolerant Xanthomonas perforans. In vitro, metallic copper from CS-Cu and FQ-Cu at 100 MUg/ml killed the copper-tolerant X. perforans strain within 1 h of exposure. In contrast, none of the micron-sized copper rates (100 to 1,000 MUg/ml) from Kocide 3000 significantly reduced copper-tolerant X. perforans populations after 48 h of exposure compared with the water control (P < 0.05). All copper-based treatments killed the copper-sensitive X. perforans strain within 1 h. Greenhouse studies demonstrated that all copper composites significantly reduced bacterial spot disease severity when compared with copper mancozeb and water controls (P < 0.05). Although there was no significant impact on yield, copper composites significantly reduced disease severity when compared with water controls, using 80% less metallic copper in comparison with copper mancozeb in field studies (P < 0.05). This study highlights the discovery that copper composites have the potential to manage copper-tolerant X. perforans and tomato bacterial spot. PMID- 28990483 TI - Identification of a Hypervirulent Pathotype of Rice yellow mottle virus: A Threat to Genetic Resistance Deployment in West-Central Africa. AB - Rice yellow mottle virus (RYMV) causes high losses to rice production in Africa. Several sources of varietal high resistance are available but the emergence of virulent pathotypes that are able to overcome one or two resistance alleles can sometimes occur. Both resistance spectra and viral adaptability have to be taken into account to develop sustainable rice breeding strategies against RYMV. In this study, we extended previous resistance spectrum analyses by testing the rymv1-4 and rymv1-5 alleles that are carried by the rice accessions Tog5438 and Tog5674, respectively, against isolates that are representative of RYMV genetic and pathogenic diversity. Our study revealed a hypervirulent pathotype, named thereafter pathotype T', that is able to overcome all known sources of high resistance. This pathotype, which is spatially localized in West-Central Africa, appears to be more abundant than previously suspected. To better understand the adaptive processes of pathotype T', molecular determinants of resistance breakdown were identified via Sanger sequencing and validated through directed mutagenesis of an infectious clone. These analyses confirmed the key role of convergent nonsynonymous substitutions in the central part of the viral genome linked protein to overcome RYMV1-mediated resistance. In addition, deep sequencing analyses revealed that resistance breakdown does not always coincide with fixed mutations. Actually, virulence mutations that are present in a small proportion of the virus population can be sufficient for resistance breakdown. Considering the spatial distribution of RYMV strains in Africa and their ability to overcome the RYMV resistance genes and alleles, we established a resistance breaking risk map to optimize strategies for the deployment of sustainable and resistant rice lines in Africa. PMID- 28990484 TI - Adult Plant Leaf Rust Resistance Derived from Toropi Wheat is Conditioned by Lr78 and Three Minor QTL. AB - Leaf rust caused by Puccinia triticina is an important disease of wheat in many regions worldwide. Durable or long-lasting leaf rust resistance has been difficult to achieve because populations of P. triticina are highly variable for virulence to race-specific resistance genes, and respond to selection by resistance genes in released wheat cultivars. The wheat cultivar Toropi, developed and grown in Brazil, was noted to have long-lasting leaf rust resistance that was effective only in adult plants. The objectives of this study were to determine the chromosome location of the leaf rust resistance genes derived from Toropi in two populations of recombinant inbred lines in a partial Thatcher wheat background. In the first population, a single gene with major effects on chromosome 5DS that mapped 2.2 centimorgans distal to IWA6289, strongly reduced leaf rust severity in all 3 years of field plot tests. This gene for adult plant leaf rust resistance was designated as Lr78. In the second population, quantitative trait loci (QTL) with small effects on chromosomes 1BL, 3BS, and 4BS were found. These QTL expressed inconsistently over 4 years of field plot tests. The adult plant leaf rust resistance derived from Toropi involved a complex combination of QTL with large and small effects. PMID- 28990486 TI - Nodule-Specific Cysteine-Rich Peptides Negatively Regulate Nitrogen-Fixing Symbiosis in a Strain-Specific Manner in Medicago truncatula. AB - Medicago truncatula shows a high level of specificity when interacting with its symbiotic partner Sinorhizobium meliloti. This specificity is mainly manifested at the nitrogen-fixing stage of nodule development, such that a particular bacterial strain forms nitrogen-fixing nodules (Nod+/Fix+) on one plant genotype but ineffective nodules (Nod+/Fix-) on another. Recent studies have just begun to reveal the underlying molecular mechanisms that control this specificity. The S. meliloti strain A145 induces the formation of Fix+ nodules on the accession DZA315.16 but Fix- nodules on Jemalong A17. A previous study reported that the formation of Fix- nodules on Jemalong A17 by S. meliloti A145 was conditioned by a single recessive allele named Mtsym6. Here we demonstrate that the specificity associated with S. meliloti A145 is controlled by multiple genes in M. truncatula, including NFS1 and NFS2 that encode nodule-specific cysteine-rich (NCR) peptides. The two NCR peptides acted dominantly to block rather than promote nitrogen fixation by S. meliloti A145. These two NCR peptides are the same ones that negatively regulate nitrogen-fixing symbiosis associated with S. meliloti Rm41. PMID- 28990485 TI - There is a need for new systemic sclerosis subset criteria. A content analytic approach. AB - OBJECTIVES: Systemic sclerosis (SSc) is heterogenous. The objectives of this study were to evaluate the purpose, strengths and limitations of existing SSc subset criteria, and identify ideas among experts about subsets. METHODS: We conducted semi-structured interviews with randomly sampled international SSc experts. The interview transcripts underwent an iterative process with text deconstructed to single thought units until a saturated conceptual framework with coding was achieved and respondent occurrence tabulated. Serial cross-referential analyses of clusters were developed. RESULTS: Thirty experts from 13 countries were included; 67% were male, 63% were from Europe and 37% from North America; median experience of 22.5 years, with a median of 55 new SSc patients annually. Three thematic clusters regarding subsetting were identified: research and communication; management; and prognosis (prediction of internal organ involvement, survival). The strength of the limited/diffuse system was its ease of use, however 10% stated this system had marginal value. Shortcomings of the diffuse/limited classification were the risk of misclassification, predictions/generalizations did not always hold true, and that the elbow or knee threshold was arbitrary. Eighty-seven percent use more than 2 subsets including: SSc sine scleroderma, overlap conditions, antibody-determined subsets, speed of progression, and age of onset (juvenile, elderly). CONCLUSIONS: We have synthesized an international view of the construct of SSc subsets in the modern era. We found a number of factors underlying the construct of SSc subsets. Considerations for the next phase include rate of change and hierarchal clustering (e.g. limited/diffuse, then by antibodies). PMID- 28990487 TI - GABA, A Primary Metabolite Controlled by the Gac/Rsm Regulatory Pathway, Favors a Planktonic Over a Biofilm Lifestyle in Pseudomonas protegens CHA0. AB - In Pseudomonas protegens CHA0 and other fluorescent pseudomonads, the Gac/Rsm signal transduction pathway is crucial for the expression of secondary metabolism and the biological control of fungi, nematodes, and insects. Based on the findings of a previous metabolomic study, the role of intracellular gamma aminobutyrate (GABA) as a potential signal in the Gac/Rsm pathway was investigated herein. The function and regulation of a gabDT (c01870-c01880) gene cluster in strain CHA0 were described. The gabT gene encoded GABA transaminase (GABAT) and enabled the growth of the bacterium on GABA, whereas the upstream gabD gene (annotated as a gene encoding succinic semialdehyde dehydrogenase) had an unknown function. A gacA mutant exhibited low GABAT activity, leading to the markedly greater intracellular accumulation of GABA than in the wild type. In the gacA mutant, the RsmA and RsmE proteins caused translational gabD repression, with concomitant gabT repression. Due to very low GABAT activity, the gabT mutant accumulated GABA to high levels. This trait promoted a planktonic lifestyle, reduced biofilm formation, and favored root colonization without exhibiting the highly pleiotropic gacA phenotypes. These results suggest an important role of GABA in the Gac/Rsm-regulated niche adaptation of strain CHA0 to plant roots. PMID- 28990488 TI - The MicroRNA miR773 Is Involved in the Arabidopsis Immune Response to Fungal Pathogens. AB - MicroRNAs (miRNAs) are 21- to 24-nucleotide short noncoding RNAs that trigger gene silencing in eukaryotes. In plants, miRNAs play a crucial role in a wide range of developmental processes and adaptive responses to abiotic and biotic stresses. In this work, we investigated the role of miR773 in modulating resistance to infection by fungal pathogens in Arabidopsis thaliana. Interference with miR773 activity by target mimics (in MIM773 plants) and concomitant upregulation of the miR773 target gene METHYLTRANSFERASE 2 (MET2) increased resistance to infection by necrotrophic (Plectosphaerrella cucumerina) and hemibiotrophic (Fusarium oxysporum, Colletototrichum higginianum) fungal pathogens. By contrast, both MIR773 overexpression and MET2 silencing enhanced susceptibility to pathogen infection. Upon pathogen challenge, MIM773 plants accumulated higher levels of callose and reactive oxygen species than wild-type plants. Stronger induction of defense-gene expression was also observed in MIM773 plants in response to fungal infection. Expression analysis revealed an important reduction in miR773 accumulation in rosette leaves of plants upon elicitor perception and pathogen infection. Taken together, our results show not only that miR773 mediates pathogen-associated molecular pattern-triggered immunity but also demonstrate that suppression of miR773 activity is an effective approach to improve disease resistance in Arabidopsis plants. PMID- 28990489 TI - Binding characterization of the targeting drug AIMPILA to AFP receptors in human tumor xenografts. AB - The main objective of this study was the characterization of preclinical tumor models based on their expression of alpha-fetoprotein receptor (RECAF) for targeting cancer cells with a new non-covalent complex (AIMPILA) containing alpha fetoprotein as the carrier and Atractyloside as an apoptosis-inducing agent. For that purpose, we measured the amount of RECAF in the homogenates of the grafted tumors T47D and SW620 and in HepG2 cell extracts. We also determined the alpha fetoprotein binding specificity of the targeting drug AIMPILA using a solid-phase chemiluminescent assay with AIMPILA-Acrdidinium. We found that RECAF is practically absent from healthy mice tissues (100 Units/mg) where in malignant cells, the amount of alpha-fetoprotein receptors follows this order: T47D (9152 Units/mg) > HepG2 (4865 Units/mg) > SW620 (2839 Units/mg). This agrees with our findings regarding AIMPILA-induced tumor growth inhibition (T47D (T/C = 22%) > HepG2 (T/C = 51%) > SW620 (T/C = 70%), where T/C is the ratio of tumor volume in treated vs control animals). Our results demonstrate that the therapeutic response to the targeting drug AIMPILA strongly depends on the RECAF expression by human tumors and confirms the choice of the tumor models used for an AIMPILA preclinical study. PMID- 28990490 TI - Targeted photodynamic therapy as potential treatment modality for the eradication of colon cancer and colon cancer stem cells. AB - Colorectal cancer is commonly treated by tumour resection, as chemotherapy and radiation have proven to be less effective, especially if the tumour has metastasized. Resistance to therapies occurs in almost all patients with colorectal cancer, especially in those with metastatic tumours. Cancer stem cells have the ability to self-renew, and their slow rate of cycling enhances resistance to treatment and increases the likelihood of tumour recurrence. Most metastatic tumours are unable to be surgically removed, thus creating a need for treatment modalities that target cancers directly and destroy cancer stem cells. Photodynamic therapy involves a photosensitizer that when exposed to a light source of a particular wavelength becomes excited and produces a form of oxygen that kills cancer cells. Photodynamic therapy is currently being investigated as a treatment modality for colorectal cancer, and new studies are exploring enhancing photodynamic therapy efficacy with the aid of drug carriers and immune conjugates. These modifications could prove effective in targeting cancer stem cells that are thought to be resistant to photodynamic therapy. In order for photodynamic therapy to be an effective treatment in colorectal cancer, it requires treatment of both primary tumours and the metastatic secondary disease that is caused by colon cancer stem cells. This review focuses on current photodynamic therapy treatments available for colorectal cancer and highlights proposed actively targeted photosynthetic drug uptake mechanisms specifically mediated towards colon cancer stem cells, as well as identify the gaps in research which need to be investigated in order to develop a combinative targeted photodynamic therapy regime that can effectively control colorectal cancer primary and metastatic tumour growth by eliminating colon cancer stem cells. PMID- 28990491 TI - Young Athletes Cleared for Sports Participation After Anterior Cruciate Ligament Reconstruction: How Many Actually Meet Recommended Return-to-Sport Criterion Cutoffs? AB - Study Design Prospective cohort study. Background While meeting objective criterion cutoffs is recommended prior to return to sports following anterior cruciate ligament (ACL) reconstruction, the number of young athletes who meet recommended cutoffs and the impact of cutoffs on longitudinal sports participation are unknown. Objectives To test the hypothesis that a higher proportion of young athletes who meet recommended cutoffs will maintain the same level of sports participation over the year following return-to-sport clearance compared to those who do not meet recommended cutoffs. Methods At the time of return-to-sport clearance, the International Knee Documentation Committee Subjective Knee Evaluation Form (IKDC), quadriceps and hamstring strength limb symmetry index (LSI), and single-leg hop test LSI were assessed. Proportions of participants who met individual (IKDC score of 90 or greater; strength and hop test LSIs of 90% or greater) and combined cutoffs were calculated. Proportions of participants who continued at the same level of sports participation over the year following return-to-sport clearance (assessed using the Tegner activity scale) were compared between those who met and did not meet cutoffs. Results Participants included 115 young athletes (88 female). The proportions meeting individual cutoffs ranged from 43.5% to 78.3%. The proportions meeting cutoffs for all hop tests, all strength tests, and all combined measures were 53.0%, 27.8%, and 13.9%, respectively. A higher proportion of participants who met cutoffs for both strength tests maintained the same level of sports participation over the year following return-to-sport clearance than those who did not (81.3% versus 60.2%, P = .02). Conclusion The proportions of young athletes after ACL reconstruction recently cleared for return to sports who met the combined criterion cutoffs were low. Those who met the criterion cutoffs for both strength tests maintained the same level of sports participation at higher proportions than those who did not. Level of Evidence Prognosis, level 2b. J Orthop Sports Phys Ther 2017;47(11):825-833. Epub 7 Oct 2017. doi:10.2519/jospt.2017.7227. PMID- 28990492 TI - Presidential Address: 28th Annual Scientific Sessions of the Society for Vascular Medicine. PMID- 28990493 TI - Remembering Alan T. Hirsch, MD, MSVM: SVM Founding Member and Past President (1954-2017). PMID- 28990494 TI - 28th SVM Scientific Sessions Highlights. PMID- 28990495 TI - Internal mammary artery-to-pulmonary vasculature fistula: Systematic review of case reports. AB - The formation of a fistula between the internal mammary artery and the pulmonary vasculature (IMA-to-PV) is a rare anomaly. The etiology can be congenital; however, most recent cases have been associated with coronary artery bypass grafting, trauma, inflammatory conditions, chronic infections, or neoplasia. The knowledge base on the formation of these fistulas is derived primarily from case reports. To our knowledge, no systematic reviews or guidelines are available that provide information on how to manage these cases, and the treatment of an IMA-to PV fistula is controversial. To our knowledge, this report is the first to review 80 cases of IMA-to-PV fistulas reported in the literature. We describe the etiologies, clinical presentation, and management of these fistulas. PMID- 28990496 TI - Bone Marrow Findings Secondary to Antineoplastic Compounds: Hematopoietic, Bone, and Cytokine Cross Talk. AB - New medullary bone formation has been observed in rats administered a variety of antineoplastic compounds. Similar effects reported in rats administered granulocyte colony-stimulating factor (G-CSF) were attributed to exaggerated pharmacology of G-CSF as a cytokine and growth factor, resulting in stromal proliferation in addition to the intended hematopoietic effects. Similar phenomena of marrow stromal change are reported among other species in association with various growth factors. Case study summaries of test item related histopathologic changes in bone marrow, reflecting trabecular and/or endosteal new bone formation, are presented. In each of these cases, it was concluded that the new medullary bone and stromal proliferation did not reflect a primary target-related toxicity; rather, the mesenchymal changes were attributed to nonspecific, secondary effects of cytokines elaborated in response to primary cytotoxic effects on hematopoietic cells with subsequent impact on circulating blood cells. The common features associated with marrow stromal changes in the case studies, as well as with a variety of pharmacologic compounds across several species described in the literature, are hematologic effects and/or changes in growth factor levels and cytokine expression. PMID- 28990497 TI - CALR, JAK2 and MPL mutation status in Argentinean patients with BCR-ABL1- negative myeloproliferative neoplasms. AB - OBJECTIVES: To establish the frequency of JAK2, MPL and CALR mutations in Argentinean patients with BCR-ABL1-negative myeloproliferative neoplasms (MPN) and to compare their clinical and haematological features. METHODS: Mutations of JAK2V617F, JAK2 exon 12, MPL W515L/K and CALR were analysed in 439 Argentinean patients with BCR-ABL1-negative MPN, including 176 polycythemia vera (PV), 214 essential thrombocythemia (ET) and 49 primary myelofibrosis (PMF). RESULTS: In 94.9% of PV, 85.5% ET and 85.2% PMF, we found mutations in JAK2, MPL or CALR. 74.9% carried JAK2V617F, 12.3% CALR mutations, 2.1% MPL mutations and 10.7% were triple negative. In ET, nine types of CALR mutations were identified, four of which were novel. PMF patients were limited to types 1 and 2, type 2 being more frequent. DISCUSSION: In ET, patients with CALR mutation were younger and had higher platelet counts than those with JAK2V617F and triple negative. In addition, JAK2V617F patients had high leucocyte and haemoglobin values compared with CALR-mutated and triple-negative patients. In PMF, patients with mutant CALR were associated with higher platelet counts. CONCLUSION: Our study underscores the importance of JAK2, MPL and CALR genotyping for accurate diagnosis of patients with BCR-ABL1-negative MPN. PMID- 28990498 TI - Tumoral vascular pattern in renal cell carcinoma and fat-poor renal angiomyolipoma as a novel helpful differentiating factor on contrast-enhanced CT scan. AB - Our objective was to evaluate the differences between tumoral vascular pattern of renal cell carcinoma and fat-poor angiomyolipoma by contrast-enhanced computed tomography. All included patients had a definitive pathological diagnosis of either angiomyolipoma or renal cell carcinoma, and then the contrast-enhanced computed tomography images of these patients were evaluated. The patients who had visible prominent vessels in cross-sectional imaging were selected. The tumor vascular pattern (prominent (>2 mm) intratumoral and peritumoral vessels), density, and diameter of the vessels in renal cell carcinoma and fat-poor angiomyolipoma were evaluated. All cases (n = 12) with fat-poor angiomyolipoma were found to have intratumoral vessels and all cases (n = 36) with clear cell renal cell carcinoma were found to have peritumoral vessels. There was no significant correlation detected between the diameter of tumor and the density as well as diameter of the vessels. In conclusion, the evaluation of the vascular pattern using contrast enhancement contrast-enhanced computed tomography may provide important information that is useful in helping accurate differential diagnosis of fat-poor angiomyolipoma or renal cell carcinoma preoperatively. PMID- 28990499 TI - Editorial:Engineered Particles and Human Tissues for Pharmaceutical Research. PMID- 28990500 TI - Editorial: Pharmaceutical Applications of Dendrimers. PMID- 28990501 TI - Editorial: Parasite Polyamines. PMID- 28990502 TI - Editorial: Recent Advances and Innovative Strategies Applied in the Development of Biomaterials. PMID- 28990503 TI - Effects of isolated isoflavones intake on health AB - Isoflavones are naturally occurring flavonoids characterized by a structure able to exert non-steroidal estrogen-like activity on human cells. The atypical linkage between the rings B and C remarkable influences these potentialities and confers them specific applications, along with the biochemical modification such as acetylation and malonylation. Plants belonging to Leguminosae family are the most abundant and rich sources for human organism, where, after their ingestion and metabolization, they show positive health effects on several diseases, especially in the prevention of coronary heart and neurological diseases, hormone related cancers, osteoporosis, and postmenopausal symptoms. Although these molecules have been the subjects of numerous researches, their role for the wellness of the human organism remains controversial, due to the estrogen-like effects that can be a risk to certain individuals, especially, for instance, women with breast cancer or with the possibility to contract it. Moreover, there are substantial inconsistencies between the results obtained by epidemiologic studies conducted on Eastern population, which found high health promoting properties, and Western clinical trials, which found much less positive effects. In this review, we have performed a critical evaluation of available literature as far as isoflavones health promoting properties, risk assessment and mechanisms of action are of concern. In addition, we supply useful information on its biochemical properties, sources and bioavailability. PMID- 28990504 TI - Polyphenols in Food: Cancer Prevention and Apoptosis Induction. AB - Polyphenols are group of water-soluble organic compounds, mainly of natural origin. The compounds having about 5-7 aromatic rings and more than 12 phenolic hydroxyl groups are classified as polyphenols. These are the antioxidants which protect the body from oxidative damage. In plants, they are the secondary metabolites produced as a defense mechanism against stress factors. Antioxidant property of polyphenols is suggested to provide protection against many diseases associated with reactive oxygen species (ROS), including cancer. Various studies carried out across the world have suggested that polyphenols can inhibit the tumor generation, induce apoptosis in cancer cells and interfere in progression of tumors. This group of wonder compounds is present in surplus in natural plants and food products. Intake of polyphenols through diet can scavenge ROS and thus can help in cancer prevention. The plant derived products can also be used along with conventional chemotherapy to enhance the chemopreventive effects. The present review focuses on various in vitro and in vivo studies carried out to assess the anti-carcinogenic potential of polyphenols present in our food. Also, the pathways involved in cancer chemopreventive effects of various subclasses (flavonoids, lignans, stilbenes and phenolic acids) of polyphenols are discussed. PMID- 28990505 TI - Biological therapy of hematologic malignancies: toward a chemotherapy-free era. AB - Less than 70 years ago, the vast majority of hematologic malignancies were untreatable diseases with fatal prognoses. The development of modern chemotherapy agents, which had begun after the Second World War, was markedly accelerated by the discovery of the structure of DNA and its role in cancer biology and tumor cell division. The path travelled from the first temporary remissions observed in children with acute lymphoblastic leukemia treated with single-agent antimetabolites until the first cures achieved by multi-agent chemotherapy regimens was incredibly short. Despite great successes, however, conventional genotoxic cytostatics suffered from an inherently narrow therapeutic index and extensive toxicity, which in many instances limited their clinical utilization. In the last decade of the 20th century, increasing knowledge on the biology of certain malignancies resulted in the conception and development of first molecularly targeted agents designed to inhibit specific druggable molecules involved in the survival of cancer cells. Advances in technology and genetic engineering enabled the production of structurally complex anticancer macromolecules called biologicals, including therapeutic monoclonal antibodies, antibody-drug conjugates and antibody fragments. The development of drug delivery systems (DDSs), in which conventional drugs were attached to various types of carriers including nanoparticles, liposomes or biodegradable polymers, represented an alternative approach to the development of new anticancer agents. Despite the fact that the antitumor activity of drugs attached to DDSs was not fundamentally different, the improved pharmacokinetic profiles, decreased toxic side effects and significantly increased therapeutic indexes resulted in their enhanced antitumor efficacy compared to conventional (unbound) drugs. Approval of the first immune checkpoint inhibitor for the treatment of cancer in 2011 initiated the era of cancer immunotherapy. Checkpoint inhibitors, bispecific T cell engagers, adoptive T-cell approaches and cancer vaccines have joined the platform so far, represented mainly by recombinant cytokines, therapeutic monoclonal antibodies and immunomodulatory agents. In specific clinical indications, conventional drugs have already been supplanted by multi-agent, chemotherapy-free regimens comprising diverse immunotherapy and/or targeted agents. The very distinct mechanisms of the anticancer activity of new immunotherapy approaches not only call for novel response criteria, but also might fundamental change treatment paradigms of certain types of hematologic malignancies in the near future. PMID- 28990506 TI - Metabolomic heterogeneity of urogenital tract cancers analyzed by complementary chromatographic techniques coupled with mass spectrometry. AB - BACKGROUND: In regard to urogenital tract cancer studies, an estimated 340,650 new cases and 58,360 deaths from genital system cancer and about 141,140 new cases and 29330 deaths from urinary system were projected to occur in United States in 2012. The main drawbacks of currently available diagnostic tests constitute the low specificity, costliness and quite high invasiveness. OBJECTIVE: The main goal of this pilot study was to determine and compare urine metabolic fingerprints in urogenital tract cancer patients and healthy controls. METHOD: A comparative analysis of the metabolic profile of urine from 30 patients with cancer of the genitourinary system (bladder (n=10), kidney (n=10) and prostate (n=10)) and 30 healthy volunteers as a control group was provided by LC TOF/MS and GC-QqQ/MS. The data analysis was performed by the use of U-Mann Whitney test or Student's t-test, principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA). RESULTS: As a result, 33, 43, and 22 compounds were identified as statistically significant in bladder, prostate and kidney cancer, respectively, comparing to healthy groups. CONCLUSION: Diverse compounds such as purine, sugars, amino acid, nucleosides, organic acid which play a role in purine metabolism, in tricarboxylic acid cycle, in amino acid metabolism or in gut floral metabolism were identified. Only two metabolites namely glucocaffeic acid and lactic acid were found to be in common in studied three types of cancer. PMID- 28990507 TI - Metabolomics and heart diseases: from basic to clinical approach. AB - The field of metabolomics has been steadily increasing in size for the last 15 years. Advances in analytical and statistical methods have allowed metabolomics to flourish in various areas of medicine. Cardiovascular diseases are some of the main research targets in metabolomics, due to their social and medical relevance, and also to the important role metabolic alterations play in their pathogenesis and evolution. Metabolomics has been applied to the full spectrum of cardiovascular diseases: from patient risk stratification to myocardial infarction and heart failure. However - despite the many proof-of-concept studies describing the applicability of metabolomics in the diagnosis, prognosis and treatment evaluation in cardiovascular diseases - it is not yet used in routine clinical practice. Recently, large phenome centers have been established in clinical environments, and it is expected that they will provide definitive proof of the applicability of metabolomics in clinical practice. But there is also room for small and medium size centers to work on uncommon pathologies or to resolve specific but relevant clinical questions. In this review, we will introduce metabolomics, cover the metabolomic work done so far in the area of cardiovascular diseases and point to future directions that may lead to its application in the clinical setting. PMID- 28990508 TI - Biomarkers of atrial fibrillation in hypertension. AB - It is well known that atrial fibrillation (AF) is the most frequent cardiac arrhythmia worldwide and substantially increases the risk for thromboembolic disease. One of the main problems is that it remains undiagnosed (about 20% of all cases of AF). On the other hand, hypertension amplifies the risk for both AF occurrences through hemodynamic and non-hemodynamic mechanisms and cerebrovascular ischemia. Under this prism, prompt diagnosis of undetected AF in hypertensive patients is of pivotal importance. Biomarkers could be used in AF diagnosis as well as in predicting the transition of paroxysmal AF to sustained AF. Last year's many biomarkers has been developed and they can categorized into electrophysiological, morphological, and molecular markers that reflect the underlying mechanisms of adverse atrial remodeling that constitutes the hallmark of this arrhythmia. In this review study, we focused on P-wave duration and dispersion as electrophysiological markers of AF and left atrial (LA) and LA appendage size, atrial fibrosis, left ventricular hypertrophy, aortic stiffness and connexins as structural biomarkers, respectively. The heterogeneous group of molecular biomarkers of AF encompasses products of the neurohormonal cascade, including. NT-pro BNP, BNP, MR-pro ANP, polymorphisms of the ACE and convertases such as corin and furin that are implemented in BNP modulation. In addition, soluble biomarkers of inflammation (i.e. CRP, IL-6) and fibrosis (i.e. TGF-1 and matrix metalloproteinases) were assessed for predicting AF. The reviewed individual biomarkers should add to current diagnostic tools but the ideal candidate is expected to combine multiple indices of atrial remodeling in order to effectively detect both AF and adverse characteristics of high risk hypertensive patients. PMID- 28990509 TI - Potential of plant-sourced phenols for inflammatory bowel disease. AB - Inflammatory bowel disease (IBD) is an uncontrolled chronic inflammatory intestinal disorder, which requires medications for long-term therapy. Facing the challenges of severe side effects and drug resistance of conventional medications, to develop the strategies meet the stringent safety and effectiveness in the long-term treatment are urgent in the clinics. In this regard, a growing body of evidence confirms plant-sourced phenols, such as flavonoids, catechins, stilbenes, coumarins, quinones, lignans, phenylethanoids, cannabinoid phenols, tannins, phenolic acids and hydroxyphenols, exert potent protective benefits with fewer undesirable effects in conditions of acute or chronic intestinal inflammation through improvement of colonic oxidative and pro inflammatory status, preservation of the epithelial barrier function and modulation of gut microbiota. In this review, the great potential of plant sourced phenols and their action mechanisms for the treatment or prevention of IBD in recent research are summarized, which may help the further development of new preventive/adjuvant regimens for IBD. PMID- 28990510 TI - Benzothiazole-based compounds in antibacterial drug discovery. AB - Numerous compounds with a benzothiazole scaffold that have been described in the literature show promising activities against several Gram-positive and Gram negative bacteria, and also against Mycobacterium tuberculosis. Benzothiazole based antibacterial compounds bind to different biological targets in bacterial cells and have been shown to be inhibitors of enzymes that are important for essential processes in the bacterial cells, such as cell-wall synthesis, cell division, and DNA replication, or are important for different biosynthetic pathways of essential compounds in bacterial cells, such as the biosynthesis of histidine and biotin. This review focuses on the antibacterial potential of benzothiazole-based compounds, in terms of their specific interactions with targets in bacterial cells. We assess the importance of the benzothiazole scaffold in the discovery of new antibacterial compounds, the potential of benzothiazole-based compounds against resistant bacterial strains, optimization of their antibacterial activity, and the future perspectives of benzothiazole based antibacterials. PMID- 28990511 TI - Sunitinib in the treatment of thyroid cancer. AB - BACKGROUND: Sunitinib (SU11248) is an oral, small-molecule, multi-targeted tyrosine kinase inhibitor (TKI), that inhibits receptors for platelet-derived growth factor (PDGF-Rs) and vascular endothelial growth factor receptors (VEGFRs), c-KIT, fms-related tyrosine kinase 3 (FLT3) and RET. The concurrent inhibition of these pathways reduces tumor vascularization and causes cancer cell apoptosis, inducing a tumor shrinkage. Sunitinib is approved for the treatment of imatinib-resistant gastrointestinal stromal tumor (GIST), renal carcinoma, and pancreatic neuroendocrine tumors. METHODS: We searched the literature on PubMed library. RESULTS: In vitro studies showed that sunitinib targeted the cytosolic MEK/ERK and SAPK/JNK pathways in the RET/PTC1 cell inhibiting cell proliferation and causing stimulation of sodium/iodide symporter (NIS) gene expression in RET/PTC1 cells. Furthermore sunitinib is active in vitro and in vivo against anaplastic thyroid cancer (ATC) cells. Most of the clinical studies report that sunitinib is effective as first- and second-line TKI therapy in patients with advanced dedifferentiated thyroid cancer (DeTc), or medullary thyroid cancer (MTC). Sunitinib 37.5 mg/day is well tolerated, and effective. The most common adverse events include decreases in blood cell counts (especially leukocytes), diarrhea, fatigue, hand-foot skin reaction, nausea, musculoskeletal pain, and hypertension. CONCLUSION: Even if sunitinib is promising in the therapy of differentiated thyroid carcinoma (DTC), until now no phase III studies have been published, and additional prospective researches are necessary in order to evaluate the real efficacy of sunitinib in aggressive thyroid cancer. PMID- 28990512 TI - Fighting type-2 diabetes: present and future perspectives. AB - BACKGROUND: Type-2 diabetes mellitus accounts for 80-90% of diabetic patients. So far, the treatment of diabetes mainly aims at elevating insulin level and lowering glucose level in the peripheral blood and mitigating insulin resistance. Physiologically, insulin secretion from pancreatic beta cells is delicately regulated. Thus, how insulin-related therapies could titrate blood glucose appropriately and avoid the occurrence of hypoglycemia remains an important issue for decades. Similar question is addressed on how to attenuate vascular complication in diabetic subjects. METHOD: We overviewed the evolution of each class of anti-diabetic drugs that have been used in clinical practice, focusing on their mechanisms, clinical results and cautions. RESULTS: Glucagon-like peptide-1 receptor agonists stimulate beta cells for insulin secretion in response to diet but not in fasting stage, which make them superior than conventional insulin-secretion stimulators. DPP-4 inhibitors suppress glucagon like peptide-1 degradation. Sodium/glucose cotransporter 2 inhibitors enhance glucose clearance through urine excretion. The appearance of these new drugs provides new thoughts on glycemic control. We update the clinical findings of Glucagon-like peptide-1 receptor agonists, DPP-4 inhibitors and Sodium/glucose cotransporter 2 inhibitors in glycemic control and the risk or progression of cardiovascular disease in diabetic patients. Stem cell therapy might be an alternative tool for diabetic patients to improve beta cell regeneration and peripheral ischemia. We summarizes the clinical results of mesenchymal stem cells transplanted into patients with diabetic limb and foot. CONCLUSION: A stepwise intensification of dual and triple therapy for individual diabetic patient is required to achieve therapeutic target. PMID- 28990513 TI - Protective effects of the caffeine against neurodegenerative diseases. AB - Caffeine is one of the most consumed stimulant of the central nervous system. Similar to those of other stimulants, its effects are to improve brain activity and stimulate cognition learning and memory. Caffeine affects the brain by acting mainly as a non-selective blocker of the adenosine receptors (A1, A2A, A2B, and A3). The purpose of this review article is to provide an overview on the neurobiochemical impact of caffeine, focusing on the ability of the drug to effectively counteract several neurodegenerative disorders such as Alzheimer's, Parkinson's, Huntington's diseases, Multiple sclerosis and Amyotrophic lateral sclerosis and Epilepsy. What emerges is a significant therapeutic and prophylactic potentiality of caffeine because of its antioxidant activity combined with multiple molecular targets. Moreover, it is striking to note that a molecule such as caffeine, appeared in the land plants few billion years ago may be an efficient drug for cells of more recent evolutionary origin. PMID- 28990514 TI - Bisphenol A in Reproduction: Epigenetic Effects. AB - BACKGROUND: Bisphenol A (BPA) is an endocrine disrupting chemical widely used in the manufacture of polycarbonate plastic and epoxy resin to produce a multitude of consumer products, food and drink containers, and medical devices. BPA is similar to estradiol in structure and thus interferes in steroid signalling with different outcomes on reproductive health depending on doses, life stage, mode, and timing of exposure. In this respect, it has an emerging and controversial role as a "reproductive toxicant" capable of inducing short and long-term effects including the modulation of gene expression through epigenetic modification (i.e. methylation of CpG islands, histone modifications and production of non-coding RNA) with direct and trans-generational effects on exposed organisms and their offspring, respectively. OBJECTIVE: This review provides an overview about BPA effects on reproductive health and aims to summarize the epigenetic effects of BPA in male and female reproduction. RESULTS: BPA exerts epigenetic effects in both male and female reproduction. In males, BPA affects spermatogenesis and sperm quality and possible trans-generational effects on the reproductive ability of the offspring. In females, BPA affects ovary, embryo development, and gamete quality for successful in vivo and in vitro fertilization (IVF). CONCLUSION: The exact mechanisms of BPA-mediated effects in reproduction are not fully understood; however, the environmental exposure to BPA - especially in fetal and neonatal period - deserves attention to preserve the reproductive ability in both sexes and to reduce the epigenetic risk for the offspring. PMID- 28990515 TI - Recent Advances and Perspectives in Liposomes for Cutaneous Drug Delivery. AB - The cutaneous route is attractive for the delivery of drugs in the treatment of a wide variety of diseases. However the stratum corneum (SC) is an effective barrier that hampers skin penetration. Within this context, liposomes emerge as a potential carrier for improving topical delivery of therapeutic agents. In this review, we aimed to discuss key aspects for the topical delivery by drug-loaded liposomes. Phospholipid type and phase transition temperature have been shown to affect liposomal topical delivery. The effect of surface charge is subject to considerable variation depending on drug and composition. In addition, modified vesicles with the presence of components for permeation enhancement, such as surfactants and solvents, have been shown to have a considerable effect. These liposomes include: Transfersomes, Niosomes, Ethosomes, Transethosomes, Invasomes, coated liposomes, penetration enhancer containing vesicles (PEVs), fatty acids vesicles, Archaeosomes and Marinosomes. Furthermore, adding polymeric coating onto liposome surface could influence cutaneous delivery. Mechanisms of delivery include intact vesicular skin penetration, free drug diffusion, permeation enhancement, vesicle adsorption to and/or fusion with the SC, trans-appendageal penetration, among others. Finally, several skin conditions, including acne, melasma, skin aging, fungal infections and skin cancer, have benefited from liposomal topical delivery of drugs, with promising in vitro and in vivo results. However, despite the existence of some clinical trials, more studies are needed to be conducted in order to explore the potential of liposomes in the dermatological field. PMID- 28990516 TI - Gut Microbiota as a Therapeutic Target for Metabolic Disorders. AB - BACKGROUND: Gut microbiota play a vital role not only in the digestion and absorption of nutrients, but also in homeostatic maintenance of host immunity, metabolism and the gut barrier. Recent evidence suggests that gut microbiota alterations contribute to the pathogenesis of metabolic disorders. OBJECTIVE AND METHOD: In this review, we discuss the association between the gut microbiota and metabolic disorders, such as obesity, type 2 diabetes mellitus and non-alcoholic fatty liver disease, and the contribution of relevant modulating interventions, focusing on recent human studies. RESULTS: Several studies have identified potential causal associations between gut microbiota and metabolic disorders, as well as the underlying mechanisms. The effects of modulating interventions, such as prebiotics, probiotics, fecal microbiota transplantation, and other new treatment possibilities on these metabolic disorders have also been reported. CONCLUSION: A growing body of evidence highlights the role of gut microbiota in the development of dysbiosis, which in turn influences host metabolism and disease phenotypes. Further studies are required to elucidate the precise mechanisms by which gut microbiota-derived mediators induce metabolic disorders and modulating interventions exert their beneficial effects in humans. The gut microbiota represents a novel potential therapeutic target for a range of metabolic disorders. PMID- 28990517 TI - Anesthetic Agents and Neuronal Autophagy. What We Know and What We Don't. AB - BACKGROUND: Ethanol is known to have both gamma-Aminobutyric acid agonist and Nmethyl- D-aspartate antagonist characteristics similar to commonly used volatile anesthetic agents. Recent evidence demonstrates that autophagy can reduce the development of ethanol induced neurotoxicity. Recent studies have found that general anesthesia can cause longterm impairment of both mitochondrial morphogenesis and synaptic transmission in the developing rat brain, both of which are accompanied by enhanced autophagy activity. Autophagy may play an important role in general anesthetic mediated neurotoxicity. METHODS: This review outlines the role of autophagy in the development of anesthetic related neurotoxicity and includes an explanation of the role of autophagy in neuronal cell survival and death, the relationship between anesthetic agents and neuronal autophagy, possible molecular and cellular mechanisms underlying general anesthetic agent induced activation of neuronal autophagy in the developing brain, and potential therapeutic approaches aimed at modulating autophagic pathways. RESULTS: In a time- and concentration-dependent pattern, general anesthetic agents can disrupt intracellular calcium homeostasis which enhances both autophagy and apoptosis activation. The degree of neural cell injury may be ultimately determined by the interplay between autophagy and apoptosis. It appears likely that the increase in calcium flux associated with some anesthetic agents disrupts lysosomal function. This results in an over-activation of endosomal- lysosomal trafficking causing mitochondrial damage, reactive oxygen species upregulation, and lipid peroxidation. CONCLUSION: Autophagy may play a role in the development of anesthetic related neurotoxicity. Understanding this may lead to strategies or therapies aimed at preventing or ameliorating general anesthetic agent mediated neurotoxicity. PMID- 28990518 TI - Click Reactions in Chemistry of Triterpenes - Advances Towards Development of Potential Therapeutics. AB - Triterpenoids are natural compounds with a large variety of biological activities such as anticancer, antiviral, antibacterial, antifungal, antiparazitic, antiinflammatory and others. Despite their low toxicity and simple availability from the natural resources, their clinical use is still severely limited by their higher IC50 and worse pharmacological properties than in the currently used therapeutics. This fact encouraged a number of researchers to develop new terpenic derivatives more suitable for the potential clinical use. This review summarizes a new approach to improve both, the activity and ADME-Tox properties by connecting active terpenes to another modifying molecules using click reactions. Within the past few years, this synthetic approach was well explored yielding a lot of great improvements of the parent compounds along with some less successful attempts. A large quantity of the new compounds presented here are superior in both activity and ADME-Tox properties to their parents. This review should serve the researchers who need to promote their hit triterpenic structures towards their clinical use and it is intended as a guide for the chemical synthesis of better drug candidates. PMID- 28990519 TI - Amino Acid Degrading Enzymes and Their Application in Cancer Therapy. AB - Amino acids are essential components in various biochemical pathways. The deprivation of certain amino acids is an antimetabolite strategy for the treatment of amino acid-dependent cancers which exploits the compromised metabolism of malignant cells. This review summarizes recent progress in the relationship between amino acids metabolism and cancer therapy, with a particular focus on L-asparagine, L-methionine, L-arginine and L-lysine degrading enzymes and their formulations, which have been successfully used in the treatment of several types of cancer. PMID- 28990520 TI - Collagenolytic enzymes and their applications in biomedicine. AB - Nowadays, enzymatic therapy is a very promising line of treatment for many different diseases. There is a group of disorders and conditions, caused by fibrotic and scar processes and associated with the excessive accumulation of collagen that needs to be catabolized to normalize the connective tissue content. The human body normally synthesizes special extracellular enzymes, matrix metalloproteases (MMPs) by itself. These enzymes can cleave components of extracellular matrix (ECM) and different types of collagen and thus maintain the balance of the connective tissue components. MMPs are multifunctional enzymes and are involved in a variety of organism processes. However, under pathological conditions, the function of MMPs is not sufficient, and these enzymes fail to deal with disease. Thus, medical intervention is required. Enzymatic therapy is a very effective way of treating such collagen-associated conditions. It involves the application of exogenous collagenolytic enzymes that catabolize excessive collagen at the affected site and lead to the successful elimination of disease. Such collagenolytic enzymes are synthesized by many organisms: bacteria, animals (especially marine organisms), plants and fungi. The most studied and commercially available are collagenases from Clostridium histolyticum and from the pancreas of the crab Paralithodes camtschatica, due to their ability to effectively hydrolyse human collagen without affecting other tissues, and their wide pH ranges of collagenolytic activity. In the present review, we summarize not only the data concerning existing collagenase-based medications and their applications in different collagen-related diseases and conditions, but we also propose collagenases from different sources for their potential application in enzymatic therapy. PMID- 28990521 TI - The Use of Naphthoquinones and Furano-naphthoquinones as Anti-invasive Agents. AB - Cancer is a leading cause of mortality in the world and metastasis is to blame. Invasion is the initial step of metastasis. Therapies targeting epithelial mesenchymal transition (EMT), cancer stem cells (CSCs) and signal transducer and activator of transcription 3 (STAT3) signaling pathways can reduce stemness of cancer cells and thus inhibit cancer invasion. A large number of anti-cancer naphthoquinones (NQs) can target cancer invasion by acting on EMT, CSCs and STAT3 signaling. Furano-naphthoquinones (FNQs) belong to a class of NQ derivatives commonly characterized by a naphthoquinone fused with a furano ring. A study indicated that the corporation of the furano ring improved the anticancer potency as compared to the other classes of NQs. BBI608, a natural FNQ, which can be found in the woods or barks of several Tabebuia species, has entered phases I and II clinical trials. It has been regarded as a potential candidate for new generation lead compound acting directly on CSCs to overcome the chemotherapy resistance. Apart from the natural plant sources, there are a number of synthetic FNQ derivatives that are effective in reducing stemness of cancer cells and thus are anti-invasive. In this review, the anti-invasion mechanisms of NQs and the more powerful FNQs, together with their natural origins, synthetic derivatives as well as their synthetic routes are discussed. PMID- 28990522 TI - Untargeted metabolomics provides insight into mechanisms underlying resistant hypertension. AB - BACKGROUND: Resistant hypertension (RH) affects about 15-20% of treated hypertensive patients worldwide. RH increases the risk of cardiovascular events such as myocardial infarction and stroke by 50%. The pathological mechanisms underlying resistance to treatment are still poorly understood. OBJECTIVE: The main goal of this pilot study was to determine and compare plasma metabolomic profiles in resistant and non-resistant hypertensive patients. METHOD: We applied untargeted metabolomic profiling in plasma samples collected from 69 subjects with RH and 81 subjects with controlled hypertension. To confirm patients' compliance to antihypertensive treatment, levels of selected drugs and their metabolites were determined in plasma samples with the LC-ESI-TOF/MS technique. RESULTS: The results showed no statistically significant differences of antihypertensive drug administration in the compared groups. We identified 19 up regulated and 13 down-regulated metabolites in RH. CONCLUSION: The metabolites altered in RH are linked to oxidative stress and inflammation, endothelium dysfunction, vasoconstriction, and cell proliferation. Our results may generate new hypothesis about RH development and progression. PMID- 28990523 TI - Editorial: Modifying Cardiovascular Risk Factors: Acquired Topics and Emerging Concepts. PMID- 28990524 TI - Statins and inflammation in cardiovascular disease. AB - BACKGROUND: Chronic inflammation and immune system activation underlie a variety of seemingly unrelated cardiac conditions including not only atherosclerosis and the subsequent coronary artery disease but also peripheral artery disease, hypertension with target organ damage and heart failure. The beneficial effects of HMG-CoA reductase inhibitors or statins are mainly attributed to their ability to inhibit hepatic cholesterol biosynthesis. Beyond their lipid lowering activity, ample evidence exists in support of their potent anti-inflammatory properties which initiate from the inhibition of GTPase isoprenylation, activating a cataract of secondary pathways and extend to the inhibition and blocking of immune cell activation and interaction. OBJECTIVE: To summarize the anti-inflammatory mechanisms of statins in clinical and experimental settings in cardiovascular disease. METHODS: A systematic search of PubMed and the Cochrane Database was conducted in order to identify the majority of trials, studies, current guidelines and novel articles related to the subject. RESULTS: In vitro, statins have immuno-modulatory and anti-inflammatory effects, and they can exert anti-atherosclerotic effects independently of their hypolipidemic actions. In addition, positive results have emerged from mechanistic and experimental studies on the active role of HMG-CoA reductase inhibitors in HF. By extrapolating those data in clinical setting, we further understand how HMG-CoA reductase inhibitors can beneficially affect not only systolic but also diastolic HF. CONCLUSION: In this review article, we present the basic pathophysiologic data supporting the anti-inflammatory actions of statins in clinical and experimental settings and we link these mechanisms with confirmatory clinical data on the potent non lipid lowering effects of HMG-CoA reductase inhibitors. PMID- 28990525 TI - A Human Proximal Tubular Epithelial Cell Model to Explore a Knowledge Gap on Neonatal Drug Disposition. AB - BACKGROUND: Finding the right drug-dosage for neonates is still a challenge. Until now, neonatal doses are extrapolated from adults and children doses. However, there are differences between neonatal and adult kidney physiology that should be considered, especially when it comes to drug metabolism and/or transport. Studying renal drug disposition in neonates is limited by the lack of reliable human cell models. OBJECTIVE: To illustrate the feasibility of developing an in vitro model for neonatal proximal tubule epithelial cells (nPTECs) to study renal drug disposition at this age. METHOD: nPTECs were isolated from urine samples of neonates of different gestational ages and were conditionally immortalized using a temperature sensitive SV40T antigen and human telomerase hTERT. Cell clones were characterized on gene expression level for PTEC markers such as P-glycoprotein (ABCB1), aquaporin1 (AQP1), and organic cation transport protein 2 (SLC22A2), and for kidney progenitor cell and podocyte markers. In addition, protein expression and functional assessment were performed for P-gp and OCT2. RESULTS: We established 101 clonal cell lines of conditionally immortalized nPTECs derived from neonatal urines. Characterization of primary cells lines showed expression of genes from different cell types such as progenitors, PTECs and podocytes, however the developed conditionally immortalized nPTECs only expressed proximal tubule markers. Quantitative PCR analysis confirmed the expression of proximal tubule markers in nPTECs similar to the adult control PTECs. P-gp was expressed in nPTECs derived from the different gestational ages with a similar functionality compared with adult derived PTECs. In contrast, OCT2 functionality was significantly lower in nPTEC cell lines compared with adult PTECs. CONCLUSION: We demonstrate the feasibility of culturing proximal tubule epithelial cells with high efficiency from urine of neonates. These cells expressed PTEC-specific genes and functional drug transporters. The cell model presented is a valuable tool to study proximal tubule physiology and pharmacology in newborns. In addition, we demonstrate the physiological differences between the neonatal and adult kidney, which emphasizes the importance of studying drug disposition in neonatal models instead of extrapolating from adult data. PMID- 28990526 TI - PBPK in Preterm and Term Neonates: A Review. AB - INTRODUCTION: The neonatal population remains one of the populations in which appropriate dosing regimens are still lacking, resulting in a large off-label or unlicensed use. Clinical research in these small infants remains a challenge, which sparks the need for modeling and simulation as an additional tool for neonatal drug research. METHODS: The use of physiologically based pharmacokinetic modeling in preterm and term neonates is investigated. RESULTS: Throughout the last decade, the use of this modeling technique in this vulnerable population has received increased attention, but still many knowledge gaps exist. Firstly, an overview of the top-down, bottom-up and middle-out approach is given, and then these different modeling tools regarding feasibility and appropriate use are compared. The challenges in applying PBPK to this young population are highlighted and possible solutions are presented. Examples of applications were found in literature and a preference for the combination of a pure bottom- up approach with clinical data (the "middle-out" approach) was detected. CONCLUSION: Perspectives to further apply this powerful modeling methodology in this population are described in order to become 'the tool' for the design of First-in Human and First-in-Neonate trials, and the individualization of dosing in these therapeutic orphans. PMID- 28990527 TI - Epilepsy, Comorbidities and Treatments. AB - BACKGROUND: An increasing amount of evidence suggests an association between epilepsy and multiple somatic and psychiatric conditions, which is more significant than in the general population. Furthermore, a bidirectional association has been established between epilepsy and several conditions, notably depression and suicide, cerebrovascular disease, stroke, dementia and migraine, which is best explained by the presence of common underlying mechanisms and risk factors. Gaining knowledge about these common mechanisms can provide insight into new therapeutic targets, screening and preventive measures. METHODS: This review discusses several of the more significant somatic and psychiatric comorbidities of epilepsy, the mechanisms and direction of their association, as well as the implications of these comorbidities for treatment. RESULTS: Somatic and psychiatric comorbidity in epilepsy have been investigated in several population based studies using medical records databases and different survey methods. All show a significantly higher prevalence for a number of medical conditions in people with epilepsy (PWE) compared to the general population. CONCLUSION: The coexistence of different medical conditions with epilepsy carries important implications for the assessment of the burden of the disease and the outcome and management of these patients, as they often require long-term antiepileptic drug intake. PMID- 28990528 TI - Level V Metastasis, a Novel Predicative Factor for Recurrence in N1b Papillary Thyroid Carcinoma. AB - BACKGROUND: Lymph nodal (LN) metastasis, classified as pN1b, is considered as an independent poor prognostic factor for Papillary thyroid carcinoma (PTC) patients. However, whether LN metastasis can serve as a predictive factor for recurrence or disease-free survival of N1b PTC is still plagued by controversy. METHODS: The N1b PTC patients who underwent total thyroidectomy and unilateral modified radical neck dissection (MRND) by the same surgical team in Ningbo NO.2 Hospital from March, 1998 to March, 2015 were included in this study. The clinical and pathological characteristics of each patient were recorded in detail. Univariate and multivariate Cox proportional hazards regression models were performed to analyze the associations between clinicopathological characteristics with recurrence. Kaplan-Meier analysis and log-rank test were used for the analysis of overall RFS and level V metastasis. RESULTS: A total of 214 patients were eligible for the final analyses. Of the 214 finally included patients with N1b PTC, 39 patients were classified with recurrence and 175 without recurrence. The final univariate and multiple Cox proportional hazards analysis only suggested level V metastasis as the independent predictive factor of N1b PTC recurrence (HR: 4.11; 95% CI:1.22-11.05, P=0.028). The patients with level V metastasis showed a significantly lower 10-year RFS rate (P=0.031) as illustrated by Kaplan-Meier analysis and log-rank test. CONCLUSION: Level V metastasis is a novel indicator for tumor recurrence and 10-year RFS in patients with N1b PTC. PMID- 28990529 TI - Review on the Application of Mixed-mode Chromatography for Separation of Structure Isoforms. AB - Proteins often generate structure isoforms naturally or artificially due to, for example, different glycosylation, disulfide scrambling, partial structure rearrangement, oligomer formation or chemical modification. The isoform formations are normally accompanied by alterations in charged state or hydrophobicity. Thus, isoforms can be fractionated by reverse-phase, hydrophobic interaction or ion exchange chromatography. We have applied mixed-mode chromatography for fractionation of isoforms for several model proteins and observed that cation exchange Capto MMC and anion exchange Capto adhere columns are effective in separating conformational isoforms and self-associated oligomers. PMID- 28990530 TI - Isoform Separation by a Mixed-mode Resin, TOYOPEARL MX-Trp-650M. AB - TOYOPEARL particles are cross-linked hydroxylated methacrylic polymers available in different pore and particle sizes. They are conjugated with different ligands to generate ion-exchange, hydrophobic interaction and affinity resins. They have excellent physical and chemical properties. A mixed-mode resin, TOYOPEARL MX-Trp 650M, is made of this particle with tryptophan conjugated via N-terminal amino group and hence has both hydrophobic/aromatic side chain and carboxyl group. In this review, I will summarize the properties of the TOYOPEARL particles and MX Trp-650M resin and application of this resin for purification of proteins and in some detail the separation of disulfide (SS)- scrambled oligomers of insulin-like growth factor-1 (IGF-1). For this particular application, the intact IGF-1 was used to examine binding and elution conditions of TOYOSCREEN MX-Trp-650M column. Strong binding was obtained at pH 4.0, at which arginine, but not NaCl, resulted in elution. Both NaCl and arginine resulted in elution at pH 6.5. In addition, a pH gradient from 4.0 to 8.5 was effective. When applied to SS-scrambled IGF-1 oligomers, both pH and arginine gradient exhibited an efficient separation of the oligomers. PMID- 28990532 TI - A Novel SCN9A Mutation (F826Y) in Primary Erythromelalgia Alters the Excitability of Nav1.7. AB - BACKGROUND: Primary erythromelalgia (PE) is a dominant inherited disorder characterized by recurrent pain, redness, and warmth of the extremities that is caused by gain-of-function mutations in Nav1.7 encoding gene SCN9A. Most of the PE-causing mutations of Nav1.7 have been shown to be able to render Nav1.7 expressing cells hyperexcitable, however in most PE cases the symptoms are refractory to treatment with sodium channel blockers and the mechanism underlying the intractability has not been clearly clarified. OBJECTIVE: To identify the mutation of SCN9A in a Chinese Han family with typical symptoms of PE and study the electrophysiological effect of the identified mutation. METHODS: A Chinese Han family with typical symptoms of PE was collected and the proband's response to treatment was recorded. All the exons and flanking intronic sequences of SCN9A were amplified with PCR and sequenced. Several online programs were used to predict the damaging effect of variants. The functional effect of variants was studied by voltage-clamp analysis in CHO-K1 cells. RESULTS: The PE symptoms of the proband are refractory to all kinds of reported medications. Sequence analysis of SCN9A showed that a novel c.2477T>A (p. F826Y) mutation co-segregated with the disease phenotype. Several online programs predicted that the F826Y mutation has a deleterious effect on the gene product. Voltage-clamp analysis showed that while compared with the wild-type channel, activation of the F826Y mutant channel was shifted by 7.7 mV in a hyperpolarizing direction, whereas steadystate inactivation was shifted by 4.3 mV in a depolarizing direction. CONCLUSION: A novel disease-causing SCN9A Mutation (F826Y) was identified in a Chinese family with typical PE symptoms refractory to treatment. F826Y of Nav1.7 could render DRG neurons hyperexcitable, contributing to the pathogenesis of PE. PMID- 28990531 TI - RUNX1: A Regulator of NF-kB Signaling in Pulmonary Diseases. AB - Runt-related transcription factor 1 (RUNX1), a member of the RUNX family, is one of the key regulatory proteins in vertebrates. RUNX1 is involved in embryonic development, hematopoiesis, angiogenesis, tumorigenesis and immune response. In the past few decades, studies mainly focused on the effect of RUNX1 on acute leukemia and cancer. Only few studies about the function of RUNX1 in the pathological process of pulmonary diseases have been reported. Recent studies have demonstrated that RUNX1 is highly expressed in both mesenchymal and epithelial compartments of the developing and postnatal lung and that it plays a critical role in the lipopolysaccharide induced lung inflammation by regulating the NF-kB pathway. RUNX1 participates in the regulation of the NF-kB signaling pathway through interaction with IkB kinase complex in the cytoplasm or interaction with the NF-kB subunit P50. NF-kB is well-known signaling pathway necessary for inflammatory response in the lung. This review is to highlight the RUNX1 structure, isoforms and to present the mechanism that RUNX1 regulates NF kB. This will illustrate the great potential role of RUNX1 in the inflammation signaling pathway in pulmonary diseases. PMID- 28990533 TI - Blood-brain Barrier Disruption Leads to Postoperative Cognitive Dysfunction. AB - BACKGROUND: Postoperative Cognitive Dysfunction (POCD) has received considerable attention as one of the main postoperative complications. The underlying mechanism of POCD in elderly subjects has not been fully elucidated to date. The Central Nervous System (CNS) is isolated from the bloodstream by the Blood Brain Barrier (BBB) that consists of endothelial cells, capillary blood vessels and tight junctions. The tight junctions carry out significant biological functions that are associated with the CNS and blood circulation. METHODS: In this review, I present a hypothesis that blood-brain barrier disruption leads to postoperative cognitive dysfunction. A total of 81 healthy male Wistar rats were used for the present study. All the experimental animals were randomly divided into 3 groups: normal control group, isoflurane group and splenectomy group. The control group was not subjected to any form of treatment. The rats in isoflurane group were given 1.5-2% isoflurane under intubation and mechanical ventilation. The rats in splenectomy group underwent splenectomy under the same anesthesia as the isoflurane group. The Morris water maze was used to examine the learning and memory ability of the animals. The expression of the Tight Junctions Proteins (TJPs) in the hippocampus was analyzed using Western blotting. The concentration of Evans Blue (EB) in the supernatant was analyzed using UV spectroscopy. Ultrastructure changes in the basal laminas, the Tight Junctions (TJs), mitochondria and the endoplasmic reticulum surrounding the capillaries were assessed by Transmission Electron Microscopy (TEM). RESULTS: Following splenectomy, the rats displayed concomitant significant cognitive deficits in the Morris water maze test. Taken together, the results indicate that the expression levels of occludin (65KD) following splenectomy were reduced on days one and three in aged rats. No significant difference was noted in the expression levels of claudin-5, except for a reduction after surgery on day one. The leakage of EB was higher following splenectomy than control group and isoflurane group. The ultrastructure of the neurovascular unit was monitored on the day prior to surgery and on the 1st, 3rd and 7th day following surgery using a transmission electronmicroscope. CONCLUSION: The alterations in the levels of tight junction proteins following splenectomy may contribute to the BBB permeability increase, which in turn will induce postoperative cognitive dysfunction. PMID- 28990534 TI - Association between Vitamin D Status, Oxidative Stress Biomarkers and Viral Load in Human Immunodeficiency Virus Type 1 Infection. AB - BACKGROUND: The role of vitamin D in the pathophysiology of human immunodeficiency virus type 1 (HIV-1) infection is still unclear. OBJECTIVE: To evaluate the associations between vitamin D and immunological, virological, and oxidative stress biomarkers in individuals with human immunodeficiency virus type 1 (HIV-1) infection. METHODS: The serum levels of 25 hydroxyvitamin D [25(OH)D] were determined in 314 HIV-1- infected individuals and 127 controls and the values >=30 ng/mL defined a vitamin D sufficient (VDS) status, and <30 ng/mL defined the presence of hypovitaminosis D (HD). Oxidative stress was evaluated with plasma levels of lipid hydroperoxides, advanced oxidation protein products (AOPP), carbonyl protein, nitric oxide metabolites (NOx), total radical-trapping antioxidant parameter (TRAP), and sulfhydryl groups of proteins. Plasma HIV-1 viral load and CD4+/CD8+ T cells were quantified. RESULTS: The 25(OH)D levels and vitamin D status did not differ between HIV-1-infected individuals and controls. Hydroperoxides and AOPP were higher (p<0.0001 and p=0.002, respectively), whereas TRAP, carbonyl protein, and NOx were lower in HIV-1-infected individuals than controls (p<0.0001). HIV-1-infected individuals with HD showed higher hydroperoxide levels than those with a VDS status (p=0.012) and controls (p=0.022), independent of ethnicity and antiretroviral therapy. A positive correlation between 25(OH)D >=30 ng/mL and viral load was observed when expressed as the number of copies/mL (r=0.178, p=0.039), as well as log10 copies/mL (r=0.183, p=0.033). CONCLUSION: These results suggest the bimodal influence of vitamin D in the modulation of immune response in HIV-1 infection, considering its differential susceptibility to modulation of the various immune targets and pathways. PMID- 28990535 TI - Voluntary Medical Male Circumcision to Prevent HIV in Tanah Papua, Indonesia: Field Trial to Assess Acceptability and Feasibility. AB - BACKGROUND: Relatively little attention has been paid to the significant HIV prevention role that voluntary medical male circumcision (VMMC) can play in populations with moderate levels of HIV prevalence. One such location is Tanah Papua, Indonesia, which in 2013 had a general population having HIV prevalence of 2.3% concentrated among indigenous Papuans (2.9% prevalence), very few of whom are circumcised. This article reports the findings of an implementation research study assessing the acceptability and feasibility of introducing VMMC for HIV prevention. METHODS: Following a situational assessment and socialization of targeted groups of men and key stakeholders, a single-arm, open-label, prospective cohort trial using the non-surgical PrePex(r) device was undertaken in four cities. Study participants were recruited via study-associated socialization events. Data were collected from clients prior to and following device insertion, and at several "check-up" points (2-, 21- and 42-days) using standardized case report forms. A random sample of circumcision clients from one city was surveyed six months' post-removal to assess the prevalence of compensatory sexual risk behaviours. RESULTS: Demand for circumcision was weak in three of the cities, reflecting insufficient prior socialization and lingering concerns over religious appropriateness and safety issues. Despite no prior experience with PrePex (r), the pilot implementation yielded side-effect and adverse event rates that were unremarkable in comparison with sub-Saharan African countries, where PrePex (r) is widely used. No evidence of increased post procedure sexual risk-taking was found. CONCLUSION: The study findings point to both opportunity and significant challenges in introducing VMMC on a large scale in Tanah Papua, Indonesia. Although there were enough promising signs in the qualitative research and in the limited-scale implementation trial undertaken to remain optimistic as to the potential for VMMC to help contain HIV in Tanah Papua, much remains to be done to promote the benefits of VMMC and address lingering concerns as to safety and religious appropriateness. An acceleration of the pace of task-shifting from physicians to nurses will be needed in order for VMMC to be feasible for implementation on a large scale. PMID- 28990537 TI - Nanostructured Therapeutic Carriers for Tuberculosis Treatment: Approaches & Challenges. AB - BACKGROUND: The diseases tuberculosis, triggered by intracellular pathogens, is a major problem for the global medical professionals. Treatments for these diseases through conventional dosage form consist of long-term therapy with multiple drugs, leading to several side effects and contribute to low patient compliance and drug resistance. The pathogens are found to be situated in the intracellular compartments of the cells, which ultimately results in additional blockades to effective treatment. Therefore, improved and more efficient therapies for such intracellular diseases are required. METHODS: This review discusses the potential of nanomedicine and related patents to improve intracellular disease chemotherapy. To complete the objective, we searched bibliographic databases of indexed literature using a focused and structured criteria. The quality and characteristics of selected papers were assessed using standard parameters with qualitative analysis having a conceptual framework. RESULTS: Nanoparticle-based drug delivery systems are suitable for the treatment of illnesses, such as tuberculosis. Due to the unique size-dependent properties, nanocarriers such as nanoparticles, liposomes, niosomes and microspheres offer the opportunity to develop new therapeutic and diagnostic tools. The ability to integrate drugs into nanosystems displays a new standard in pharmacotherapy that could be used for cell-targeted drug therapy. Experimental data showed the possibility of intermittent chemotherapy with main antituberculosis drugs by employing nanocarriers. Besides the advantage of the controlled release of medications in organs, the other benefits of the nanocarriers include the possibility of various routes of therapy, reduction in drug dosage and adverse effects, reduced possibility of drug interactions, and drug-resistant targeting. Published literature including patented studies suggests that nanomedicine mediated drug delivery may improve tuberculosis chemotherapy by offering benefits such as targeting to the specific organs, sustained and controlled drug release, tuberculosis diagnosis, drug delivery to the pathogen's intracellular location, and tuberculosis vaccine development. CONCLUSION: The properties of nanomedicine may prove beneficial in developing improved, efficacious or alternative therapies for tuberculosis diseases. PMID- 28990536 TI - Novel Insights in the Metabolic Syndrome-induced Oxidative Stress and Inflammation-mediated Atherosclerosis. AB - CONTEXT: Atherosclerosis is a progressive pathological process and a leading cause of mortality worldwide. Clinical research and epidemiological studies state that atherosclerosis is caused by an amalgamation of metabolic and inflammatory deregulation involving three important pathological events including Endothelial Dysfunction (ED), Foam Cell Formation (FCF), and Vascular Smooth Muscle Cells (VSMCs) proliferation and migration. OBJECTIVES: Research in recent years has identified Metabolic Syndrome (MS), which involves factors such as obesity, insulin resistance, dyslipidemia and diabetes, to be responsible for the pathophysiology of atherosclerosis. These factors elevate oxidative stress and inflammation-induced key signalling molecules and various microRNAs (miRs). In present study, we have reviewed recently identified molecular targets in the pathophysiology of atherosclerosis. METHODS: Scientific literature obtained from databases such as university library, PubMed and Google along with evidences from published experimental work in relevant journals has been summarized in this review article. RESULTS: The molecular events and cell signalling implicated in atherogenic processes of ED, FCF and VSMCs hyperplasia are sequential and progressive, and involve cross talks at many levels. Specific molecules such as transcription factors, inflammatory cytokines and chemokines and miRs have been identified playing crucial role in most of the events leading to atherosclerosis. CONCLUSION: Studies associated with MS induced oxidative stress- and inflammation mediated signalling pathways along with critical miRs help in better understanding of the pathophysiology of atherosclerosis. Several key molecules discussed in this review could be potent target for the prevention and treatment of atherosclerosis. PMID- 28990538 TI - Recent Complications and Issues in Tuberculosis Treatment. AB - BACKGROUND: Tuberculosis is one of the major communicable diseases which can be prevented and cured. The prevalence of tuberculosis infection is more despite this disease causes major morbidity and mortality. To establish connection between tuberculosis (TB) related stigma and hindrance in search of a treatment after the inception of symptoms associated with tuberculosis. METHODS: Physicians conducted the interviews using a structured questionnaire. Information from the medical reports available at health care centers (especial results of sputum microscopy, radiological and other investigations) was also distracted. Patients is said to be infected with TB having a minimum two initial +ve sputum smears or one +ve sputum smear and chest radiographic abnormalities along with active pulmonary TB as determined by clinician; one sputum +ve culture specimen +ve for Mycobacterium tuberculosis. High resolution computed tomography (HRCT), a new susceptible technique shows erratically disseminated military nodules. The organs associated and extents of lesions of miliary TB in the pulmonary tuberculosis are examined by ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI). Histopathological examination of tissue biopsy is a conservative and fast technique for the separation of mycobacterium tuberculosis and assessment of choroid tubercles in fundus. CONCLUSION: Even though numerous prognostic markers have been described which envisage mortality, yet untreated miliary TB has a serious outcome within one year. A high index of clinical research, early diagnosis and timely institution of anti-tuberculosis treatment can be life-saving. Response to first-line anti-tuberculosis drugs is good. Anti tuberculosis drugs are patent. PMID- 28990539 TI - New Drugs and Vaccines for Tuberculosis. AB - BACKGROUND: Tuberculosis (TB) is an infectious disease that resulted in estimated 9.6 million new cases in 2014 and 1.5 million deaths. The available drug regimen for TB is time consuming which more often leads to the patient non compliance which then results in occurrence of drug resistant TB (Multi-drug and extremely drug resistant TB) in several portions of the world. METHODS: The dangerous combinations of TB and HIV is taking its toll on human health. The foremost factor is non- profit associated with the development of anti TB drugs. There is almost 10 different drugs in various levels of trials whereas the vaccine development is focusing more on adult vaccine rather than a child vaccine. RESULTS: More than 15 vaccine candidate are in various stages of pipelines. Present compilation gives an account for various drug candidates and vaccine products in various stages of drug development. Also included is a recent collection of patents for assay methods, potential drug candidates/classes and vaccination products. CONCLUSION: The need is for improvement in the activity and chemical and biological description of under development compounds. Lastly the set up for clinical and appropriate uses for running a reliable clinical trial is a necessary prerequisite. PMID- 28990540 TI - Current Progress in Synthesis, Characterization and Applications of Silver Nanoparticles: Precepts and Prospects. AB - BACKGROUND: Silver nanoparticles (AgNPs), are amongst the utmost striking nanosized materials that are extensively applied in a variety of biomedical applications which includes diagnostic use, disease management, medical device coating, drug delivery and for personal health care. DISCUSSION: With the growing interest and its application in the health care sector, it is becoming necessary for a better understanding and exploration of AgNPs mechanism of action like biological interaction, their possible toxicity, and safety concern to human exposure. AgNPs have been the subject of researchers attention and interest due to the unique properties and quality such as shape and size depending optical, electrical, and antimicrobial potentials (antibacterial, antifungal, antiviral etc.). In recent times, several studies have been conducted on AgNPs antimicrobial potential and also a number of patents related to its synthesis, clinical role and importance have also been registered. In this review, a short overview of AgNPs synthesis approach is presented (physical, chemical, and biological or green synthesis) and it also delivers a historical outlook of AgNPs application as an antimicrobial agent which includes combined evidence of microbial resistance and safety issues with human exposure. PMID- 28990542 TI - Psychopharmacological options for adult patients with anorexia nervosa: the patients' and carers' perspectives integrated by the spectrum model. PMID- 28990541 TI - Associations of dietary patterns with bone mass, muscle strength and balance in a cohort of Australian middle-aged women. AB - Influences of dietary patterns on musculoskeletal health are poorly understood in middle-aged women. This cross-sectional analysis from a cohort of 347 women (aged 36-57 years) aimed to examine associations between dietary patterns and musculoskeletal health outcomes in middle-aged women. Diet was measured by the Cancer Council of Victoria FFQ. Total body bone mineral content (TB BMC), femoral neck and lumbar spine bone density (dual-energy X-ray absorptiometry), lower limbs muscle strength (LMS) and balance tests (timed up and go test, step test, functional reach test (FRT) and lateral reach test) were also measured. Exploratory factor analysis was used to identify dietary patterns and scores for each pattern generated using factor loadings with absolute values >=0.20. Associations between food pattern scores and musculoskeletal outcomes were assessed using multivariable linear regression. Three dietary patterns were identified: 'Healthy' (high consumption of a plant-based diet - vegetables, legumes, fruit, tomatoes, nuts, snacks, garlic, whole grains and low intake of high-fat dairy products), 'high protein, high fat' (red meats, poultry, processed meats, potatoes, cruciferous and dark-yellow vegetables, fish, chips, spirits and high-fat dairy products) and 'Processed foods' (high intakes of meat pies, hamburgers, beer, sweets, fruit juice, processed meats, snacks, spirits, pizza and low intake of cruciferous vegetables). After adjustment for confounders, Healthy pattern was positively associated with LMS, whereas Processed foods pattern was inversely associated with TB BMC and FRT. The associations were not significant after accounting for multiple comparisons. There were no associations with any other outcomes. These results suggest that maintaining a healthy diet could contribute to bone acquisition, muscle strength and balance in adult life. However, while they provide some support for further investigating dietary strategies for prevention of age-related loss of muscle and deterioration in balance, the exploratory nature of the analyses means that confirmation in longitudinal studies and/or trials with pre-specified hypotheses is needed. PMID- 28990543 TI - Reasons for Treatment Non-Response: A Controlled Study of Patients' Views in Pain Rehabilitation. AB - BACKGROUND: Understanding successful and unsuccessful behavioural treatment for pain is essential. AIMS: We carried out a retrospective survey of 130 people who had undergone pain rehabilitation based on acceptance and commitment therapy, aiming to identify factors associated with non-response. METHOD: The sample was selected using the reliable change index to define 'responders' and 'non responders' to key outcome measures. We surveyed a range of treatment-related, systemic, practical and personal factors that may have affected their treatment, and then compared 'non-responders' with 'responders', controlling for factors that might not be causal or specific to non-response. RESULTS: Logistic regression analysis showed two themes that distinguished the groups, 'people outside programme' and 'emotional state'. CONCLUSIONS: These data have clinical implications, as such factors can be addressed directly or incorporated into an assessment of treatment 'readiness'. This study introduced a novel methodology for the investigation of pain treatment response, which allowed a broad study of clinically relevant variables, but with greater rigour than conventional self reports of 'helpful factors' in treatment. PMID- 28990545 TI - A LONGITUDINAL ANALYSIS OF INTERNAL MIGRATION, DIVORCE AND WELL-BEING IN CHINA. AB - SummaryThe rapid economic growth in China has been accompanied by increases in internal migration as well as marital dissolution. Using longitudinal data from China Health and Nutrition Surveys covering over 19,000 individuals during 1989 2011, this study modelled the inter-relationships between internal migration, divorce and individual well-being, tackling conceptual and methodological aspects such as the joint determination of variables. First, random effects probit models showed that the migration periods of husbands and wives significantly increased their respective chances of divorce. Second, results from dynamic random effects models for self-reported health showed different effects of separation periods for husbands and wives; divorce did not significantly lower health status. Third, dynamic models for systolic and diastolic blood pressures showed significant effects of migration durations of husbands and wives; men had lower systolic blood pressure following divorce thereby indicating beneficial effects for unhappily married couples. The implications of the findings are discussed. PMID- 28990544 TI - Associations of dietary carbohydrates, glycaemic index and glycaemic load with risk of bladder cancer: a case-control study. AB - Carbohydrate foods with high glycaemic index (GI) and load (GL) may negatively influence cancer risk. We studied the association of dietary carbohydrates, GI, GL, intake of bread and pasta with risk of bladder cancer using data from an Italian case-control study. The study included 578 men and women with histologically confirmed bladder cancer and 608 controls admitted to the same hospitals as cases for acute, non-neoplastic conditions. OR were estimated by logistic regression models after allowance for relevant confounding factors. OR of bladder cancer for the highest v. the lowest quantile of intake were 1.52 (95 % CI 0.85, 2.69) for available carbohydrates, 1.18 (95 % CI 0.83, 1.67) for GI, 1.96 (95 % CI 1.16, 3.31, P trend<0.01) for GL, 1.58 (95 % CI 1.09, 2.29, P trend=0.03) for pasta and 1.92 (95 % CI 1.28, 2.86, P trend<0.01) for bread. OR for regular consumption of legumes and whole-grain products were 0.78 (95 % CI 0.60, 1.00) and 0.82 (95 % CI 0.63, 1.08), respectively. No heterogeneity in risks emerged across strata of sex. This case-control study showed that bladder cancer risk was directly associated with high dietary GL and with consumption of high quantity of refined carbohydrate foods, particularly bread. These associations were apparently stronger in subjects with low vegetable consumption. PMID- 28990546 TI - [New treatments in immuno-oncology: a revolution and a formidable scientific and clinical challenge]. PMID- 28990547 TI - [Induction of pancreatic beta-like cell regeneration by activation of GABA signaling pathways]. PMID- 28990548 TI - [The Epstein-Barr virus and the centriole: new tricks from an old dog]. PMID- 28990549 TI - [A new immune competent mouse model for the study of hepatitis D virus infection]. PMID- 28990550 TI - [Characterization of rhythmic liver physiology by nuclear proteomics]. PMID- 28990552 TI - [Mitochondria link between cannabinoid and memory]. PMID- 28990551 TI - [Hybrid fluorescent probes for imaging cellular proteins on demand]. PMID- 28990553 TI - [Anti-adenovirus humoral immunity: impact on dendritic cell activation]. PMID- 28990554 TI - [Fertilization: the spermatic nucleus unlocked by an ultra-specialized thioredoxin]. PMID- 28990555 TI - [The mystery of histone disappearance during spermatogenesis]. PMID- 28990556 TI - [Beating cancer with synthetic genes: towards more effective treatments through autonomous genetic programs]. PMID- 28990557 TI - [Evolutionary explanation of the diversity of immune strategies]. PMID- 28990558 TI - [Navbeta4: a metastasis suppressor and a new biomarker of aggressive cancers]. PMID- 28990559 TI - [Predicting placebo response with functional magnetic resonance imaging]. PMID- 28990560 TI - [Control of the Salmonella enterica virulence by iron-sulfur cluster biogenesis machinery]. PMID- 28990561 TI - [Cholestasis-induced liver injury: the role of S1PR2]. PMID- 28990562 TI - [Clone war: tumour-suppressive cell competition]. PMID- 28990563 TI - [Ribosomes synthesis at the heart of cell proliferation]. AB - Ribosomes are central to gene expression. Their assembly is a complex and an energy consuming process. Many controls exist to make it possible a fine-tuning of ribosome production adapted to cell needs. In this review, we describe recent advances in the characterisation of the links occurring between ribosome synthesis and cell proliferation control. Defects in ribosome biogenesis directly impede cellular cycle and slow-down proliferation. Among the different factors involved, we could define the 5S particle, a ribosome sub-complex, as a key regulator of p53 and other tumour suppressors such as pRB. This cross-talk between ribosome neogenesis defects and proliferation and cellular cycle also involves other cell cycle controls such as p14ARF, SRSF1 or PRAS40 pathways. These data place ribosome synthesis at the heart of cell proliferation and offer new therapeutic strategies against cancer. PMID- 28990564 TI - [MiRNAs: new actors in the physiopathology of multiple sclerosis]. AB - Multiple sclerosis (MS) is an auto-immune demyelinating disorder characterized by a chronic neuro-inflammatory process associated with an infiltration of the central nervous system (CNS) by autoreactive lymphocytes. The etiology of the disease remains unclear but the recent discovery of a dysregulated miRNA network in both cells and extracellular fluids of MS patients has brought new insights on the pathophysiological mechanisms involved in this disorder. miRNAs can induce a T cell polarization towards a pathological Th17 or Th1 phenotype and a deleterious activation of microglia, the CNS-resident macrophages. We provide here a review of the most recent data regarding miRNA dysregulation and pathophysiological roles in MS patients and in the animal model of MS, EAE (experimental autoimmune encephalomyelitis). Moreover, we discuss the putative clinical value of miRNAs as a novel biomarker and diagnostic tool for MS. PMID- 28990565 TI - [Calpain as a new therapeutic target for treating spasticity after a spinal cord injury]. AB - After a spinal cord injury (SCI), patients develop spasticity, a motor disorder characterized by hyperreflexia and stiffness of muscles. Spasticity results from alterations in motoneurons with an upregulation of their persistent sodium current (I NaP), simultaneously with a disinhibition caused by a reduction of expression of chloride (Cl-) co-transporters KCC2. Until recently the origin of alterations was unknown. After reviewing pathophysiology of spasticity, the manuscript relates our recent work showing a tight relationship between the calpain-dependent proteolysis of voltage-gated sodium channels, the upregulation of I NaP and spasticity following SCI. We also discuss KCC2 as a substrate of calpains which may contribute to the disinhibition of motoneurons below the lesion. This led us to consider the proteolytic cleavage of both sodium channels and KCC2 as the upstream mechanism contributing to the development of spasticity after SCI. PMID- 28990566 TI - [Some insulins to orchestrate growth]. AB - Body size is an intrinsic property of living organisms that is intimately linked to the developmental program to produce fit individuals with proper proportions. Final size is the result of both genetic determinants and sophisticated mechanisms adapting size to available resources. Even though organs grow according to autonomous programs, some coordination mechanisms ensure that the different body parts adjust their growth with the rest of the body. In Drosophila, Dilp8, a hormone of the Insulin/Relaxin family is a key player in this inter-organs coordination and is required together with its receptor Lgr3 to limit developmental variability. Recently, the transcriptional co-activator Yki (homologue of YAP/TAZ factors in mammals) was shown to regulate dilp8 expression and contribute to the coordination of organ growth in Drosophila. PMID- 28990567 TI - [Nuclear transfer to prevent transmission of mtDNA disorders: where are we?] AB - The recent birth from a mitochondrial DNA mutation carrier of a child, conceived after transfer in a donor oocyte of the meiotic spindle, taken from the maternal oocyte, revived the debate on the safety of these procedures. The doubts concern mainly the possibility of genetic reversion, the uncertainties about potential disturbances of the dialogue between nuclear and mitochondrial genomes and the side effects of a heteroplasmic state induced by these techniques. The possibility to expand nuclear transfer applications to patients experiencing in vitro fertilization failure, urges us to answer these questions rapidly. PMID- 28990568 TI - [Role of academic social networks in disseminating the scientific production of researchers in biology/medicine: the example of ResearchGate]. AB - Over time, academic social networks are more and more used by researchers, especially thanks to the possibilities of sharing articles they offer. The objective of the present study was to evaluate the proportion, the typology (pre print, post-print author/publisher) and the legality of the full-text publications deposited by researchers on ResearchGate which is widely used by the medical and biological community, using a sample of 1,500 randomly selected articles in PubMed and published between 2013 and 2015. To compare, the access to the full-text of the 1500 articles via PubMed and PubMed Central has been assessed, putting into evidence the important role ResearchGate plays for providing full-texts of articles in biology/medicine. It also puts academic social networks into perspective in relation to open-access repositories and open access. PMID- 28990570 TI - [Children's politics and the hierarchy dilemma]. AB - Hierarchy is a recurrent feature of social life. From an early age, children are confronted with power relationships wherein a dominant individual imposes his/her will to a subordinate individual. Recent research has shown that young children develop sophisticated abilities in understanding power. However, little is known about how young children react to power-based inequality. Do they consider a dominant should be favored so as to strenghten the status quo ? Or do they consider that the subordinate must be favored to conteract a social inequality? In the current paper, I present and discuss a recent study, published in Developmental Psychology, that investigates this issue. PMID- 28990569 TI - [History of the thymus: from an "accident of evolution" to the programming of immunological self-tolerance]. AB - This synthesis presents the most important disruptions of conceptions about the thymus since its discovery in Antique Greece. For centuries, the thymus was considered as a vestigial organ, and its role in T-lymphocyte differentiation has been proposed only in the 1960's. Most recent studies attribute to the thymus an essential and unique role in the programming of central immunological self tolerance. The basal mechanism implicated in this function is the transcription in thymic epithelium of genes encoding precursors of self-antigens. Processing of these latter leads to presentation of self-antigens by the major histocompatibility complex (MHC) machinery expressed by thymic epithelial cells and dendritic cells. During fetal life, this presentation drives negative selection of T-cell clones harboring receptors with high affinity for these MHC/self-antigen complexes. After birth, this presentation also promotes the generation of regulatory T cells specific for these complexes. A number of studies, as well as the identification of Aire and Fezf2 genes, have shown that a thymus dysfunction plays a crucial role in the development of organ-specific autoimmunity. PMID- 28990571 TI - [For an "alternative" history of the medicine]. PMID- 28990572 TI - [A misunderstanding]. PMID- 28990573 TI - [Common and rare variants, polygenic traits and missing heritability]. AB - Recently, a systematic (but limited) search for rare variants implicated in adult height, a highly polygenic trait, has uncovered a number of new variants for which the effect size is inversely correlated with the minor allele frequency. This opens interesting perspectives on the genetic architecture of complex traits and on the vexing problem of "missing heritability". PMID- 28990574 TI - An evidence-based evaluation on the use of platelet rich plasma in orthopedics - a review of the literature. AB - Within orthopedics, the use of platelet-rich plasma (PRP) has been rapidly increasing in popularity, however, its true effectiveness has yet to be fully established. Several studies find that injecting PRP to the site of injury does not provide any significant benefit with respect to clinical outcomes; however, many others report the contrary. Due to the conflicting evidence and multiple meta-analyses conducted on the topic, a literature review of high-quality evidence on the use of PRP for common orthopaedic conditions was performed. Thus far, the evidence appears to suggest that PRP may provide some benefit in patients who present with knee osteoarthritis or lateral epicondylitis. On the other hand, evidence appears to be inconsistent or shows a minimal benefit for PRP usage in rotator cuff repair, patellar and Achilles tendinopathies, hamstring injuries, anterior cruciate ligament (ACL) repair, and medial epicondylitis. There is limited confidence in the conclusions from the published meta-analyses due to issues with statistical pooling, and limited subgroup analyses exploring the substantial heterogeneity across studies. Evidence-based clinicians considering the use of PRP in their patients with musculoskeletal injuries should be weary that the literature appears to be inconsistent and thus far, inconclusive. PMID- 28990576 TI - Publication rates of abstracts presented at major interventional radiology conferences. AB - PURPOSE: We aimed to determine the publication rate and factors predictive of publication of oral presentations at the annual meetings of the Cardiovascular and Interventional Radiology Society of Europe (CIRSE) and the Society of Interventional Radiology (SIR). METHODS: Keywords and authors from oral presentation abstracts at the 2012 CIRSE and SIR annual meetings were used to search PubMed and GoogleScholar for subsequent publication. Logistic regression was performed to identify whether number of authors, country of origin, subject category, methodology, study type, and/or study results were predictive of publication. RESULTS: A total of 421 abstracts (CIRSE-126, SIR-295) met the inclusion criteria. The overall publication rate across both conferences was 44.9%. Time from conference presentation to publication was 15+/-8.9 months for CIRSE and 16.3+/-8.8 months for SIR (P > 0.05), with a combined time interval of 15.9+/-8.8 months for both. The median impact factor of published abstracts was 2.075 (interquartile range, 2.075-2.775) for CIRSE and 2.093 (2.075-2.856) for SIR (P > 0.05). The most common country of origin for published abstracts was Germany (27.1%) at CIRSE and the United States (69%) at SIR. Logistic regression did not identify factors that were predictive of future publication. CONCLUSION: Publication rates were similar for CIRSE and SIR. Factors such as country of origin, topic of study and study results were not predictive of future publication. Authors should not be discouraged from submitting their work to journals based on these factors. PMID- 28990577 TI - Manipulating magnetism by ultrafast control of the exchange interaction. AB - In recent years, the optical control of exchange interactions has emerged as an exciting new direction in the study of the ultrafast optical control of magnetic order. Here we review recent theoretical works on antiferromagnetic systems, devoted to (i) simulating the ultrafast control of exchange interactions, (ii) modeling the strongly nonequilibrium response of the magnetic order and (iii) the relation with relevant experimental works developed in parallel. In addition to the excitation of spin precession, we discuss examples of rapid cooling and the control of ultrafast coherent longitudinal spin dynamics in response to femtosecond optically induced perturbations of exchange interactions. These elucidate the potential for exploiting the control of exchange interactions to find new scenarios for both faster and more energy-efficient manipulation of magnetism. PMID- 28990575 TI - A systematic review of the concept and clinical applications of bone marrow aspirate concentrate in tendon pathology. AB - Tendon pathologies are a group of musculoskeletal conditions frequently seen in clinical practice. They can be broadly classified into traumatic, degenerative and overuse-related tendinopathies. Rotator cuff tears, Achilles tendinopathy and tennis elbow are common examples of these conditions. Conventional treatments have shown inconsistent outcomes and might fail to provide satisfactory clinical improvement. With the growing trend towards the use of mesenchymal stem cells (MSCs) in other branches of medicine, there is an increasing interest in treating tendon pathologies using the bone marrow MSC. In this article, we provide a systematic literature review documenting the current status of the use of bone marrow aspirate concentrate (BMAC) for the treatment of tendon pathologies. We also asked the question on the safety of BMAC and whether there are potential complications associated with BMAC therapy. Our hypothesis is that the use of BMAC provides safe clinical benefit when used for the treatment of tendinopathy or as a biological augmentation of tendon repair. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist while preparing this systematic review. A literature search was carried out including the online databases of PubMed, EMBASE, ClinicalTrial.gov and the Cochrane Library from 1960 to the end of May 2015. Relevant studies were selected and critically appraised. Data from eligible studies were extracted and classified per type of tendon pathology. We included 37 articles discussing the application and use of BMAC for the treatment of tendon pathologies. The Critical Appraisal Skills Program (CASP) appraisal confirmed a satisfactory standard of 37 studies. Studies were sub-categorised into: techniques of extraction, processing and microscopic examination of BMAC (n = 18), where five studies looked at the evaluation of aspiration techniques (n = 5), augmentation of rotator cuff tears (n = 5), augmentation of tendo-achilles tendon (n = 1), treatment of gluteal tendon injuries (n = 1), management of elbow epicondylitis (n = 2), management of patellar tendinopathy (n = 1) and complications related to BMAC (n = 5). Multiple experimental studies investigated the use of BMAC for tendon repair; nonetheless, there are only limited clinical studies available in this field. Unfortunately, due to the scarcity of studies, which were mainly case series, the current level of evidence is weak. We strongly recommend further future randomised controlled studies in this field to allow scientists and clinicians make evidence-based conclusions. PMID- 28990578 TI - New developments in the theoretical treatment of low dimensional strongly correlated systems. AB - We review two important non-perturbative approaches for extracting the physics of low- dimensional strongly correlated quantum systems. Firstly, we start by providing a comprehensive review of non-Abelian bosonization. This includes an introduction to the basic elements of confor- mal field theory as applied to systems with a current algebra, and we orient the reader by presenting a number of applications of non-Abelian bosonization to models with large symmetries. We then tie this technique into recent advances in the ability of cold atomic systems to realize complex symme- tries. Secondly, we discuss truncated spectrum methods for the numerical study of systems in one and two dimensions. For one dimensional systems we provide the reader with considerable insight into the methodology by reviewing canonical applications of the technique to the Ising model (and its variants) and the sine-Gordon model. Following this we review recent work on the development of renormalization groups, both numerical and analytical, that alleviate the effects of truncating the spectrum. Using these technologies, we consider a number of applications to one-dimensional systems: properties of carbon nanotubes, quenches in the Lieb-Liniger model, 1+1D quantum chro- modynamics, as well as Landau-Ginzburg theories. In the final part we move our attention to consider truncated spectrum methods applied to two-dimensional systems. This involves combining truncated spectrum methods with matrix product state algorithms. We describe applications of this method to two-dimensional systems of free fermions and the quantum Ising model, including their non equilibrium dynamics. PMID- 28990579 TI - Bone matrix production in hydroxyapatite-modified hydrogels suitable for bone bioprinting. AB - Though bioprinting is a forward-looking approach in bone tissue engineering, the development of bioinks which are on the one hand processable with the chosen printing technique, and on the other hand possess the relevant mechanical as well as osteoconductive features remains a challenge. In the present study, polymer solutions based on methacrylated gelatin and methacrylated hyaluronic acid modified with hydroxyapatite (HAp) particles (5 wt%) were prepared. Encapsulation of primary human adipose-derived stem cells in the HAp-containing gels and culture for 28 d resulted in a storage moduli significantly increased to 126% +/- 9.6% compared to the value on day 1 by the sole influence of the HAp. Additional use of osteogenic media components resulted in an increase of storage module up to 199% +/- 27.8%. Similarly, the loss moduli was increased to 370% +/- 122.1% under the influence of osteogenic media components and HAp. Those changes in rheological material characteristics indicate a distinct change in elastic and viscous hydrogel properties, and are attributed to extensive matrix production in the hydrogels by the encapsulated cells, what could also be proven by staining of bone matrix components like collagen I, fibronectin, alkaline phosphatase and osteopontin. When using the cell-laden polymer solutions as bioinks to build up relevant geometries, the ink showed excellent printability and the printed grid structure's integrity remained intact over a culture time of 28 d. Again, an intense matrix formation as well as upregulation of osteogenic markers by the encapsulated cells could be shown. In conclusion, we demonstrated that our HAp containing bioinks and hydrogels on basis of methacrylated gelatin and hyaluronic acid are on the one hand highly suitable for the build-up of relevant three dimensional geometries with microextrusion bioprinting, and on the other hand exhibit a significant positive effect on bone matrix development and remodeling in the hydrogels, as indicated by rheological measurements and staining of bone components. This makes the developed composite hydrogels an excellent material for bone bioprinting approaches. PMID- 28990580 TI - Nitrogen-doped graphene aerogel as both a sulfur host and an effective interlayer for high-performance lithium-sulfur batteries. AB - Lithium-sulfur batteries have attracted great concern because of the high theoretical capacity of sulfur (1675 mA h g-1). However, the poor electrical conductivity and volumetric expansion of sulfur along with the dissolution of lithium polysulfides largely limit their practical application. In this study, nitrogen-doped graphene aerogel (NGA) with high nitrogen content and porosity is used as a host for the impregnation of sulfur. The effects of sulfur impregnation on the specific surface area, pore volume, and microstructure of NGA supported sulfur composite (S@NGA) are well investigated. Furthermore, NGA is also processed into a NGA film, which is sandwiched between a separator and S@NGA cathode. The lithium-sulfur battery with such a configuration delivers a high reversible capacity of 1514 mA h g-1 at 0.1 C, excellent rate performance (822 mA h g-1 at 2.0 C), and good cycling stability (946 mA h g-1 at 0.5 C even after 100 cycles). The enhanced electrochemical performance can be ascribed to the introduction of the NGA interlayer, the unique interconnected porous structure, and strong interaction between the three-dimensional nitrogen-doped graphene network and the homogeneously dispersed sulfur and/or lithium polysulfides. PMID- 28990581 TI - Blinatumomab retreatment after relapse in patients with relapsed/refractory B precursor acute lymphoblastic leukemia. PMID- 28990582 TI - Non-coding RNA: a key regulator of the pathogenicity and immunity of Flaviviridae viruses infection. PMID- 28990583 TI - The ESCRT protein CHMP5 escorts alphabeta T cells through positive selection. PMID- 28990584 TI - The IgH 3' regulatory region super-enhancer does not control IgA class switch recombination in the B1 lineage. PMID- 28990585 TI - The diverse functions of the PD1 inhibitory pathway. AB - T cell activation is a highly regulated process involving peptide-MHC engagement of the T cell receptor and positive costimulatory signals. Upon activation, coinhibitory 'checkpoints', including programmed cell death protein 1 (PD1), become induced to regulate T cells. PD1 has an essential role in balancing protective immunity and immunopathology, homeostasis and tolerance. However, during responses to chronic pathogens and tumours, PD1 expression can limit protective immunity. Recently developed PD1 pathway inhibitors have revolutionized cancer treatment for some patients, but the majority of patients do not show complete responses, and adverse events have been noted. This Review discusses the diverse roles of the PD1 pathway in regulating immune responses and how this knowledge can improve cancer immunotherapy as well as restore and/or maintain tolerance during autoimmunity and transplantation. PMID- 28990586 TI - Immune checkpoint blockade in infectious diseases. AB - The upregulation of immune checkpoint molecules, such as programmed cell death protein 1 (PD1) and cytotoxic T lymphocyte antigen 4 (CTLA4), on immune cells occurs during acute infections, such as malaria, as well as during chronic persistent viral infections, including HIV and hepatitis B virus. These pathways are important for preventing immune-driven pathology but can also limit immune mediated clearance of the infection. The recent success of immune checkpoint blockade in cancer therapy suggests that targeting these pathways would also be effective for preventing and treating a range of infectious diseases. Here, we review our current understanding of immune checkpoint pathways in the pathogenesis of infectious diseases and discuss the potential for therapeutically targeting these pathways in this setting. PMID- 28990588 TI - Triglycerides cross the blood-brain barrier and induce central leptin and insulin receptor resistance. AB - OBJECTIVE: Resistance at the brain receptors for leptin and insulin has been associated with increased feeding, obesity and cognitive impairments. The causal agent for central resistance is unknown but could be derived from the blood. Here we postulate whether hypertriglyceridemia, the major dyslipidemia of the metabolic syndrome, could underlie central leptin and insulin resistance. DESIGN: We used radioactively labeled triglycerides to measure blood-brain barrier (BBB) penetration, western blots to measure receptor activation, and feeding and cognitive tests to assess behavioral endpoints. RESULTS: Human CSF was determined to contain triglycerides, a finding previously unclear. The radioactive triglyceride triolein readily crossed the BBB and centrally administered triolein and peripherally administered lipids induced in vivo leptin and/or insulin resistance at hypothalamic receptors. Central triolein blocked the satiety effect of centrally administered leptin. Decreasing serum triglycerides with gemfibrozil improved both learning and memory inversely proportionate to triglyceride levels. CONCLUSIONS: Triglycerides cross the blood-brain barrier rapidly, are found in human cerebrospinal fluid, and induce central leptin and insulin receptor resistance, decreasing satiety and cognition. PMID- 28990587 TI - Neutrophil extracellular traps in immunity and disease. AB - Neutrophils are innate immune phagocytes that have a central role in immune defence. Our understanding of the role of neutrophils in pathogen clearance, immune regulation and disease pathology has advanced dramatically in recent years. Web-like chromatin structures known as neutrophil extracellular traps (NETs) have been at the forefront of this renewed interest in neutrophil biology. The identification of molecules that modulate the release of NETs has helped to refine our view of the role of NETs in immune protection, inflammatory and autoimmune diseases and cancer. Here, I discuss the key findings and concepts that have thus far shaped the field of NET biology. PMID- 28990589 TI - Which anthropometric measures best reflect neonatal adiposity? AB - BACKGROUND: Studying the determinants and the long-term consequences of fetal adipose accretion requires accurate assessment of neonatal body composition. In large epidemiological studies, in-depth body composition measurement methods are usually not feasible for cost and logistical reasons, and there is a need to identify anthropometric measures that adequately reflect neonatal adiposity. METHODS: In a multiethnic Asian mother-offspring cohort in Singapore, anthropometric measures (weight, length, abdominal circumference, skinfold thicknesses) were measured using standardized protocols in newborn infants, and anthropometric indices (weight/length, weight/length2 (body mass index, BMI), weight/length3 (ponderal index, PI)) derived. Neonatal total adiposity was measured using air displacement plethysmography (ADP) and abdominal adiposity using magnetic resonance imaging (MRI). Correlations of the anthropometric measures with ADP- and MRI-based adiposity were assessed using Pearson's correlation coefficients (rp), including in subsamples stratified by sex and ethnicity. RESULTS: Study neonates (n=251) had a mean (s.d.) age of 10.2 (2.5) days. Correlations between ADP-based fat mass (ADPFM) and anthropometric measures were moderate (rp range: 0.44-0.67), with the strongest being with weight/length, weight, BMI and sum of skinfolds (rp=0.67, 0.66, 0.62, 0.62, respectively, all P<0.01). All anthropometric measures except skinfold thicknesses correlated more strongly with ADP-based fat-free mass than ADPFM, indicating that skinfold measures may have more discriminative power in terms of neonatal total body adiposity. For MRI-based measures, weight and weight/length consistently showed strong positive correlations (rp?0.7) with abdominal adipose tissue compartments. These correlations were consistent in boys and girls, across different ethnic groups, and when conventional determinants of neonatal adiposity were adjusted for potential confounding. Abdominal circumference was not strongly associated with ADPFM or abdominal fat mass. CONCLUSIONS: Simple anthropometric measures (weight and weight/length) correlated strongly with neonatal adiposity, with some evidence for greater discriminative power for skinfold measures. These simple measures could be of value in large epidemiological studies. PMID- 28990590 TI - An experimental therapeutics test of whether adding dissonance-induction activities improves the effectiveness of a selective obesity and eating disorder prevention program. AB - OBJECTIVE: Compare the Healthy Weight obesity and eating disorder prevention program, which promotes participant-driven gradual lifestyle changes to bring energy intake and expenditure into balance, to a new intervention, Project Health, which adds activities to create cognitive dissonance about unhealthy eating, a sedentary lifestyle, and excess body fat, and an obesity education video-control condition. METHOD: College students at risk for both outcomes because of weight concerns (N=364, 72% female) were randomized to condition, completing pretest, posttest, and 6, 12 and 24-month follow-up assessments. RESULTS: Project Health participants showed significantly smaller increases in measured body mass index (BMI) through 2-year follow-up than both Healthy Weight participants and controls (both d=-0.18), and significantly lower onset of overweight/obesity over 2-year follow-up than Healthy Weight participants and controls (13 vs 21% and 22%). Healthy Weight and Project Health participants showed significantly greater eating disorder symptom reductions than controls through 2-year follow-up. Healthy Weight and Project Health participants showed marginally lower eating disorder onset over follow-up than controls (3 and 3% vs 8% respectively). CONCLUSIONS: The reduced increases in BMI and future overweight/obesity onset for Project Health relative to both an active matched intervention and a minimal intervention control condition are noteworthy, especially given the short 6-h intervention duration. The reduction in eating disorder symptoms for Healthy Weight and Project Health relative to controls was also encouraging. Results suggest that adding dissonance-induction activities increased weight loss effects. Yet, effects for both were generally small and the eating disorder onset prevention effects were only marginal, potentially because intervention groups included both sexes, which reduced eating disorder incidence and sensitivity. PMID- 28990591 TI - Incidence of components of metabolic syndrome in the metabolically healthy obese over 9 years follow-up: the Atherosclerosis Risk In Communities study. AB - BACKGROUND: Some obese adults are not afflicted by the metabolic abnormalities often associated with obesity (the 'metabolically healthy obese' (MHO)); however, they may be at increased risk of developing cardiometabolic abnormalities in the future. Little is known about the relative incidence of individual components of metabolic syndrome (MetSyn). METHODS: We used data from a multicenter, community based cohort aged 45-64 years at recruitment (the Atherosclerosis Risk In Communities study) to examine the first appearance of any MetSyn component, excluding waist circumference. Body mass index (BMI, kg m-2) and cardiometabolic data were collected at four triennial visits. Our analysis included 3969 adults who were not underweight and free of the components of MetSyn at the initial visit. Participants were classified as metabolically healthy normal weight (MHNW), overweight (MHOW) and MHO at each visit. Adjusted hazard ratios (HR) and 95% confidence intervals were estimated with proportional hazards regression models. RESULTS: The relative rate of developing each risk factor was higher among MHO than MHNW, with the strongest association noted for elevated fasting glucose (MHO vs MHNW, HR: 2.33 (1.77, 3.06)). MHO was also positively associated with elevated triglycerides (HR: 1.63 (1.27, 2.09)), low high-density lipoprotein cholesterol (HR: 1.68 (1.32, 2.13)) and elevated blood pressure (HR: 1.54 (1.26, 1.88)). A similar, but less pronounced pattern was noted among the MHOW vs MHNW. CONCLUSIONS: We conclude that even among apparently healthy individuals, obesity and overweight are related to more rapid development of at least one cardiometabolic risk factor, and that elevations in blood glucose develop most rapidly. PMID- 28990593 TI - Riluzole Impairs Cocaine Reinstatement and Restores Adaptations in Intrinsic Excitability and GLT-1 Expression. AB - Adaptations in glutamate signaling within the brain's reward circuitry are observed following withdrawal from several abused drugs, including cocaine. These include changes in intrinsic cellular excitability, glutamate release, and glutamate uptake. Pharmacological or optogenetic reversal of these adaptations have been shown to reduce measures of cocaine craving and seeking, raising the hypothesis that regulation of glutamatergic signaling represents a viable target for the treatment of substance use disorders. Here, we tested the hypothesis that administration of the compound riluzole, which regulates glutamate dynamics in several ways, would reduce cocaine seeking in the rat self-administration and reinstatement model of addiction. Riluzole dose-dependently inhibited cue- and cocaine-primed reinstatement to cocaine, but did not affect locomotor activity or reinstatement to sucrose seeking. Moreover, riluzole reversed bidirectional cocaine-induced adaptations in intrinsic excitability of prelimbic (PL) and infralimbic (IL) pyramidal neurons; a cocaine-induced increase in PL excitability was decreased by riluzole, and a cocaine-induced decrease in IL excitability was increased to normal levels. Riluzole also reversed the cocaine-induced suppression of the high-affinity glutamate transporter 1 (EAAT2/GLT-1) in the nucleus accumbens (NAc). GLT-1 is responsible for the majority of glutamate uptake in the brain, and has been previously reported to be downregulated by cocaine. These results demonstrate that riluzole impairs cocaine reinstatement while rectifying several cellular adaptations in glutamatergic signaling within the brain's reward circuitry, and support the hypothesis that regulators of glutamate homeostasis represent viable candidates for pharmacotherapeutic treatment of psychostimulant relapse. PMID- 28990597 TI - From molecular to colloidal manganese vanadium oxides for water oxidation catalysis. AB - The spontaneous, sonication-driven conversion of a molecular manganese vanadium oxide water oxidation catalyst, (n-Bu4N)3[Mn4V4O17(OAc)3] * 3H2O, into colloidal manganese vanadium oxide particles (average particle size ca. 70 nm) together with their stability and chemical water oxidation activity is reported. The nanoparticulate metal oxide colloid (approximate composition: VMn5O10.ca. 6H2O.ca. 0.2nBu4N+) is formed spontaneously when the molecular precursor is sonicated in water. The particles show water oxidation activity when combined with CeIV as the oxidant, are stable even under highly acidic reaction conditions and can be recovered and reused. PMID- 28990598 TI - FeCl3-Catalyzed synthesis of pyrrolo[1,2-a]quinoxaline derivatives from 1-(2 aminophenyl)pyrroles through annulation and cleavage of cyclic ethers. AB - A straightforward Fe-catalyzed method for the synthesis of pyrrolo[1,2 a]quinoxalines from 1-(2-aminophenyl)pyrroles and cyclic ethers, which includes functionalization of C(sp3)-H bonds and the construction of C-C and C-N bonds, has been developed. The features of this reaction are Fe catalysis, low-cost and readily accessible starting materials. Moreover, this procedure exhibits good functional group tolerance and a series of pyrrolo[1,2-a]quinoxaline derivatives are obtained in moderate to good yields. PMID- 28990592 TI - Maternal and fetal genetic contribution to gestational weight gain. AB - BACKGROUND: Clinical recommendations to limit gestational weight gain (GWG) imply high GWG is causally related to adverse outcomes in mother or offspring, but GWG is the sum of several inter-related complex phenotypes (maternal fat deposition and vascular expansion, placenta, amniotic fluid and fetal growth). Understanding the genetic contribution to GWG could help clarify the potential effect of its different components on maternal and offspring health. Here we explore the genetic contribution to total, early and late GWG. PARTICIPANTS AND METHODS: A genome-wide association study was used to identify maternal and fetal variants contributing to GWG in up to 10 543 mothers and 16 317 offspring of European origin, with replication in 10 660 mothers and 7561 offspring. Additional analyses determined the proportion of variability in GWG from maternal and fetal common genetic variants and the overlap of established genome-wide significant variants for phenotypes relevant to GWG (for example, maternal body mass index (BMI) and glucose, birth weight). RESULTS: Approximately 20% of the variability in GWG was tagged by common maternal genetic variants, and the fetal genome made a surprisingly minor contribution to explain variation in GWG. Variants near the pregnancy-specific beta-1 glycoprotein 5 (PSG5) gene reached genome-wide significance (P=1.71 * 10-8) for total GWG in the offspring genome, but did not replicate. Some established variants associated with increased BMI, fasting glucose and type 2 diabetes were associated with lower early, and higher later GWG. Maternal variants related to higher systolic blood pressure were related to lower late GWG. Established maternal and fetal birth weight variants were largely unrelated to GWG. CONCLUSIONS: We found a modest contribution of maternal common variants to GWG and some overlap of maternal BMI, glucose and type 2 diabetes variants with GWG. These findings suggest that associations between GWG and later offspring/maternal outcomes may be due to the relationship of maternal BMI and diabetes with GWG. PMID- 28990594 TI - The Gene Encoding Protocadherin 9 (PCDH9), a Novel Risk Factor for Major Depressive Disorder. AB - Genomic analyses have identified only a handful of robust risk loci for major depressive disorder (MDD). In addition to the published genome-wide significant genes, it is believed that there are undiscovered 'treasures' underlying the current MDD genome-wide association studies (GWASs) and gene expression data sets, and digging into these data will allow better understanding of the illness and development of new therapeutic approaches. For this purpose, we performed a meta-analytic study combining three MDD GWAS data sets (23andMe, CONVERGE, and PGC), and then conducted independent replications of significant loci in two additional samples. The genome-wide significant variants then underwent explorative analyses on MDD-related phenotypes, cognitive function alterations, and gene expression in brains. In the discovery meta-analysis, a previously unidentified single-nucleotide polymorphism (SNP) rs9540720 in the PCDH9 gene was genome-wide significantly associated with MDD (p=1.69 * 10-8 in a total of 89 610 cases and 246 603 controls), and the association was further strengthened when additional replication samples were included (p=1.20 * 10-8 in a total of 136 115 cases and 355 275 controls). The risk SNP was also associated with multiple MDD related phenotypes and cognitive function impairment in diverse samples. Intriguingly, the risk allele of rs9540720 predicted lower PCDH9 expression, consistent with the diagnostic analysis results that PCDH9 mRNA expression levels in the brain and peripheral blood tissues were reduced in MDD patients compared with healthy controls. These convergent lines of evidence suggest that PCDH9 is likely a novel risk gene for MDD. Our study highlights the necessity and importance of excavating the public data sets to explore risk genes for MDD, and this approach is also applicable to other complex diseases. PMID- 28990599 TI - Ultrathin gold film modified optical properties of excitons in monolayer MoS2. AB - Metal nanostructure plays an important role in tailoring the performance of various two-dimensional semiconductors. Herein, we theoretically study the optical properties of A, B and C excitons in monolayer MoS2 coated on ultrathin gold films less than 20 nm in thickness. We show that resonances of these three excitons occur at ~660, ~613 and ~426 nm, respectively and each exciton maximizes absorption intensity at total reflection. However, because of the optical scattering effect induced by the ultrathin gold film, the maximum absorption of each exciton appears at the incident angle thetam that is larger than its corresponding surface plasmon resonance angle thetaSPR. It is possible that due to the gradual approach between thetam and thetaSPR, the maximum absorption intensity of the exciton gradually increases with thickening of the gold film. For external reflection, the C exciton maximizes absorption intensity around its corresponding quasi-Brewster's angle, whereas the incident angle, at which the A or B exciton gives the maximum absorption, gradually deviates from its corresponding quasi-Brewster's angle as the gold film thickness decreases. This discrepancy is explained by the dependencies of extinction coefficients of hybrid films on the excitonic resonance wavelength and gold film thickness. PMID- 28990600 TI - Effect of buffer at nanoscale molecular recognition interfaces - electrostatic binding of biological polyanions. AB - We investigate the impact of an over-looked component on molecular recognition in water-buffer. The binding of a cationic dye to biological polyanion heparin is shown by isothermal calorimetry to depend on buffer (Tris-HCl > HEPES > PBS). The heparin binding of self-assembled multivalent (SAMul) cationic micelles is even more buffer dependent. Multivalent electrostatic molecular recognition is buffer dependent as a result of competitive interactions between the cationic binding interface and anions present in the buffer. PMID- 28990601 TI - Direct sensing of cancer biomarkers in clinical samples with a designed nanopore. AB - Here, we show a designed solid-state nanopore sensor for the direct sensing and quantification of prostate-specific antigen (PSA) as cancer biomarker in serum without any pretreatment. This nanopore technique provides a convenient, fast, and low-cost quantification of cancer biomarkers in clinical samples. PMID- 28990602 TI - Self-sustainable, high-power-density bio-solar cells for lab-on-a-chip applications. AB - A microfluidic lab-on-a-chip system that generates its own power is essential for stand-alone, independent, self-sustainable point-of-care diagnostic devices to work in limited-resource and remote regions. Miniaturized biological solar cells (or micro-BSCs) can be the most suitable power source for those lab-on-a-chip applications because the technique resembles the earth's natural ecosystem - living organisms work in conjunction with non-living components of their environment to create a self-assembling and self-maintaining system. Micro-BSCs can continuously generate electricity from microbial photosynthetic and respiratory activities over day-night cycles, offering a clean and renewable power source with self-sustaining potential. However, the promise of this technology has not been translated into practical applications because of its relatively low power (~nW cm-2) and current short lifetimes (~a couple of hours). In this work, we enabled high-performance, self-sustaining, long-life micro-BSCs by using fundamental breakthroughs of device architectures and electrode materials. A 3-D biocompatible, conductive, and porous anode demonstrated great microbial biofilm formation and a high rate of bacterial extracellular electron transfer, which led to greater power generation. Furthermore, our micro-BSCs promoted gas exchange to the bacteria through a gas-permeable PDMS membrane in a well-controlled, tightly enclosed micro-chamber, substantially enhancing sustainability. Through photosynthetic reactions of the cyanobacteria Synechocystis sp. PCC 6803 without additional organic fuel, the 90 MUL single chambered bio-solar cell generated a maximum power density of 43.8 MUW cm-2 and sustained consistent power production of ~18.6 MUW cm-2 during the day and ~11.4 MUW cm-2 at night for 20 days, which is the highest and longest reported success of any existing micro-scale bio-solar cells. PMID- 28990603 TI - Solvothermal synthesis and enhanced photo-electrochemical performance of hierarchically structured strontium titanate micro-particles. AB - Homogeneous powders of almost spherical particles of SrTiO3 with diameters of about 1 MUm and large surface areas of up to 186 m2 g-1 were obtained from a facile one-pot solvothermal synthesis. Thorough characterization by X-ray diffraction (XRD), scanning electron microscopy (SEM), (high-resolution) transmission electron microscopy, and nitrogen physisorption measurements revealed the hierarchical architecture of the particles down to the scale of a few nanometers. In contrast to SrTiO3 samples obtained by high-temperature solid state reaction, the particles are neither agglomerated nor sintered above the micrometer scale. The samples exhibit enhanced photoelectrochemical properties in a 1.0 M KOH aqueous solution compared to their bulk counterpart. The formation mechanism of the SrTiO3 particles was systematically investigated on the basis of a series of XRD and SEM studies of the products obtained at different reaction temperatures and times. The growth of the hierarchically structured SrTiO3 particles mainly includes two stages: an intermediately formed amorphous TiO2 hydrate transforms in a subsequent step into the final SrTiO3 product. The latter step is a morphology-conserving transformation (pseudomorphosis). Further study indicates that ethylene glycol plays a dominant role in the formation of the hierarchical structures. SrTiO3 particles of polyhedral shapes with smooth surfaces are obtained when ethylene glycol is substituted by the strongly hydrated basic ionic liquid (IL) tetrabutylammonium hydroxide (TBAH) as the solvent. PMID- 28990604 TI - Electrochemically exfoliated graphene as a novel microwave susceptor: the ultrafast microwave-assisted synthesis of carbon-coated silicon-graphene film as a lithium-ion battery anode. AB - Graphene nanocomposites have attracted much attention in many applications due to their superior properties. However, preparing graphene nanocomposites requires a time-consuming thermal treatment to reduce the graphene or synthesize nanomaterials, in most cases. We present an ultrafast synthesis of a carbon coated silicon-graphene nanocomposite using a commercial microwave system. Electrochemically exfoliated graphene is used as a novel microwave susceptor to deliver efficient microwave energy conversion. Unlike graphene oxide, it does not require a time-consuming pre-thermal reduction or toxic chemical reduction to absorb microwave radiation efficiently. A carbon-coated silicon nanoparticle electrochemically exfoliated graphene nanocomposite film was prepared by a few seconds' microwave irradiation. The sp2 domains of graphene absorb microwave radiation and generate heat to simultaneously reduce the graphene and carbonize the polydopamine carbon precursor. The as-prepared N-doped carbon-coated silicon graphene film was used as a lithium-ion battery anode. The N-doped carbon coating decreases the contact resistance between silicon nanoparticles and graphene provides a wide range conductive network. Consequently, it exhibited a reversible capacity of 1744 mA h g-1 at a current density of 0.1 A g-1 and 662 mA h g-1 at 1.0 A g-1 after 200 cycles. This method can potentially be a general approach to prepare various graphene nanocomposites in an extremely short time. PMID- 28990605 TI - A simple route to 1,4-addition reactions by Co-catalyzed reductive coupling of organic tosylates and triflates with activated alkenes. AB - An efficient Co-catalyzed 1,4-addition reaction of alkyl/aryl triflates and tosylates with activated alkenes is described. In this reaction, an air-stable cobalt(ii) complex, a mild reducing agent Zn and a simple proton source (H2O) are used. A radical mechanism for the addition of alkyl tosylates to activated alkenes is likely involved. PMID- 28990606 TI - A combined docosahexaenoic acid-thyroid hormone protocol upregulates rat liver beta-Klotho expression and downstream components of FGF21 signaling as a potential novel approach to metabolic stress conditions. AB - Liver preconditioning by a docosahexaenoic acid (DHA) and triiodothyronine (T3) combined protocol underlies peroxisome-proliferator activated receptor alpha (PPARalpha)-fibroblast growth factor 21 (FGF21) upregulation, the study of the regulatory mechanisms involved being the aim of this work. Combined DHA (daily doses of 300 mg kg-1 for 3 days)-T3 (0.05 mg kg-1 at the fourth day) administration elicited higher levels of liver DHA and serum T3, with enhanced hepatic nuclear/cytosolic PPARalpha ratios, upregulation of FGF21 and beta-Klotho expression, and a small reduction in that of FGF receptor 1 (FGFR1), compared with the respective controls. Concomitantly, the components of the FGF21 cascade extracellular-signal-regulated kinase 1/2 (ERK1/2), FGF receptor substrate 2alpha (FRS2alpha), cFos, ribosomal S6 kinase 1 (RSK1), liver kinase B1 (LKB1), and AMP activated protein kinase (AMPK) were activated. The upregulation of liver PPARalpha-FGF21-AMPK signaling by the combined DHA-T3 protocol resulted in values significantly higher than those elicited by the addition of the data obtained for DHA and T3 alone. It is concluded that combined DHA-T3 supplementation achieves synergistic effects on liver PPARalpha-FGF21-AMPK signaling, which may result in significant metabolic changes associated with energy expenditure that are of importance in the treatment of obesity and other metabolic disorders. PMID- 28990607 TI - The effect of centred versus offset interpenetration on C2H2 sorption in hybrid ultramicroporous materials. AB - Fine-tuning of hybrid ultramicroporous materials (HUMs) can significantly impact their gas sorption performance. This study reveals that offset interpenetration can be antagonistic with respect to C2H2 separation from C2H2/C2H4 gas mixtures. PMID- 28990608 TI - Exploiting the energetic potential of 1,2,4-oxadiazole derivatives: combining the benefits of a 1,2,4-oxadiazole framework with various energetic functionalities. AB - A series of 1,2,4-oxadiazole-derived energetic compounds were successfully synthesized using 1,2,4-oxadiazole-3-chloroxime as a versatile starting material. These energetic compounds were fully characterized by NMR spectroscopy, IR spectroscopy, and elemental analysis. The structures of compounds 5, 6a, 6c, 8 and 8a were determined by single crystal X-ray diffraction. The physicochemical and energetic properties of all the synthesized energetic compounds, including density, thermal stability and energetic performance (e.g., detonation velocities and detonation pressures) were investigated. Among these energetic compounds, hydrazinium salts 6b and 8b and hydroxylammonium salts 6c and 8c exhibit satisfactory calculated detonation performances, which outperform the commonly used high explosive RDX. Potassium salt 5 shows good detonation performance, high density as well as high sensitivity, making it a potential primary explosive. Compound 9 is a potential candidate for melt-cast explosives due to its remarkable liquid range between melting point (Tm = 98 degrees C) and decomposition temperature (Td = 208 degrees C). PMID- 28990609 TI - Review of recent research on flexible multifunctional nanopapers. AB - Traditional paper and papermaking have struggled with a declining market during the last few decades. However, the incorporation of nanotechnology into papermaking has brought possibilities to develop low-cost, biocompatible and flexible products with sophisticated functionalities. The functionality of nanopapers emerges from the intrinsic properties of the nanofibrous network, the additional loading of specific nanomaterials (NMs), or the additional deposition and patterning of thin films of nanomaterials on the paper surface. A successful development of functional nanopapers requires understanding how the nanopaper matrix, nanofillers, nanocoating pigments, nanoprinting inks, processing additives and manufacturing processes all interact to provide the intended functionality. This review addresses the emerging area of functional nanopapers. This review discusses flexible and multifunctional nanopapers, NMs being used in nanopaper making, manufacturing techniques, and functional applications that provide new important possibilities to utilize papermaking technology. The interface where NM research meets traditional papermaking has important implications for food packaging, energy harvesting and energy storage, flexible electronics, low-cost devices for medical diagnostics, and numerous other areas. PMID- 28990610 TI - Effects of cyanidin 3-0-glucoside on cardiac structure and function in an animal model of myocardial infarction. AB - Cyanidin 3-0-glucoside (CG) is a polyphenol with potential health benefits. In this study, we investigated, for the first time, the cardioprotective effects of CG in an animal model of myocardial infarction (MI), a major cause of death worldwide. Sham and MI rats were administered CG (10 mg kg-1 day-1) daily for one week prior to surgery, and 8 weeks post-surgery. Echocardiography was performed to assess cardiac structure and function at 4 and 8 weeks. At 4 weeks, MI rats had significantly lower body mass when compared to control rats, and CG administration significantly prevented this decrease. Four-week MI rats also showed significantly increased left ventricle dilation, end systolic and end diastolic volumes in comparison to controls, and CG significantly prevented these adverse changes. Ejection fraction was significantly lower in 4-week MI rats in comparison to controls, and CG had no effect on this parameter. At 8 weeks, body mass was significantly lower in MI rats when compared to control rats, and CG significantly prevented this decrease. At 8 weeks, MI rats showed a significant increase in left ventricle dilation and isovolumic relaxation time, while ejection fraction was significantly lower when compared to controls; these parameters were not altered by CG treatment. Eight-week MI rats had significantly higher level of oxidative stress in heart tissue in comparison to controls, and CG administration did not prevent this increase. In conclusion, administration of CG was able to significantly preserve body mass in both 4 and 8 weeks MI rats, as well as significantly prevent cardiac dilation in 4 weeks MI rats. However, CG was unable to sustain this cardioprotection, as cardiac structure and function were not significantly improved in 8 weeks MI rats. PMID- 28990611 TI - Hot electron-hole plasma dynamics and amplified spontaneous emission in ZnTe nanowires. AB - Key to optimizing and tailoring the optoelectronic properties of semiconductor nanostructures for practical applications is a clear understanding of their carrier interactions and recombination dynamics. Herein, the electron-hole (e-h) plasma dynamics and the electron-phonon coupling interactions in zincblende ZnTe nanowires (NWs) were systematically investigated by time-resolved photoluminescence (TRPL) spectroscopy over a wide range of lattice temperatures (4-300 K) and pump densities. Following intense, non-resonant femtosecond (fs) laser pulse excitation, the excited carriers thermalize to quasi-equilibrium distribution through carrier-carrier and carrier-phonon scattering within a few picoseconds. The peak temperature of the hot electron gas (Te0) is much higher than the lattice temperature and increases sub-linearly with the pump fluence. The hot electron gas thermalizes in two characteristic carrier density-dependent regimes - i.e., within 35 ps under high carrier densities (e-h plasma) while persisting to 360 ps under low carrier densities (exciton). Temperature-dependent studies of the ZnTe NWs revealed that the acoustic phonons play a significant role in the cooling of the hot e-h plasma in these NWs and the emission band broadening arises from the interplay of the contributions from crystal imperfections, LA and LO phonon scattering and most importantly, from the hot carrier thermalization. For demonstration, e-h plasma-amplified spontaneous emission in ZnTe NWs at room temperature by one- and two-photon excitation was realized. The results provide new insights into carrier interactions and recombination dynamics of ZnTe NWs and highlight their potential for high efficiency e-h plasma light emitters, sensors and in plasma photochemotherapy. PMID- 28990612 TI - Controlling G-quadruplex formation via lipid modification of oligonucleotide sequences. AB - G-quadruplexes (G4) represent attractive supramolecular scaffolds. In this communication, we show that the lipid modification of a G4 prone oligonucleotide sequence drastically increases the probability of forming tetramolecular parallel G4s with unprecedented conformational control over other unspecific oligomers or folds. PMID- 28990613 TI - Effect of cooking and simulated gastrointestinal digestion on the activity of generated bioactive peptides in aged beef meat. AB - Ageing is widely used in the meat industry to improve tenderness mainly as a result of the breakdown of muscular proteins through the action of endopeptidases during storage time. In addition, meat contains a large pool of other proteolytic enzymes, mainly exopeptidases, which cut from the outer edges of proteins and polypeptides generating a vast array of peptides and free amino acids. Some of these peptides could potentially exert bioactivities of interest for human health. In this study, ACE-inhibitory and antioxidant activities during meat ageing in chilled-storage at 4 degrees C for a period of time of 0, 1, 2, 3 and 4 weeks have been determined. Beef loin steak samples were analysed before and after cooking, and gastrointestinal digestion was simulated in order to study its effect on the bioactivity. Control and cooked samples showed an increase in the ACE-inhibitory activity from the third week of chilled storage whereas non significant differences in the antioxidant activity between control and cooked samples were detected during the studied time. After gastrointestinal digestion of samples, there was a significant increment of the ACE-inhibitory and antioxidant activities in comparison with control and cooked samples at all the studied times. As a main conclusion, cooking does not significantly influence the bioactivity detected whereas the in vitro gastrointestinal digestion produces a significant increase in the ACE-inhibitory and antioxidant activities from the first week, probably due to the intense generation of small peptides as a result of the action of gastrointestinal enzymes. PMID- 28990614 TI - Microfluidic magnetic bead conveyor belt. AB - Magnetic beads play an important role in the miniaturization of clinical diagnostics systems. In lab-on-chip platforms, beads can be made to link to a target species and can then be used for the manipulation and detection of this species. Current bead actuation systems utilize complex on-chip coil systems that offer low field strengths and little versatility. We demonstrate a novel system based on an external rotating magnetic field and on-chip soft-magnetic structures to focus the field locally. These structures were designed and optimized using finite element simulations in order to create a number of local flux density maxima. These maxima, to which the magnetic beads are attracted, move over the chip surface in a continuous way together with the rotation of the external field, resulting in a mechanism similar to that of a conveyor belt. A prototype was fabricated using PDMS molding techniques mixed with iron powder for the magnetic structures. In the subsequent experiments, a quadrupole electromagnet was used to create the rotating external field. We observed that beads formed agglomerates that rolled over the chip surface, just above the magnetic structures. Field rotation frequencies between 0.1-50 Hz were tested resulting in magnetic bead speeds of over 1 mm s-1 for the highest frequency. With this, we have shown that our novel concept works, combining a simple design and simple operation with a powerful and versatile method for bead actuation. This makes it a promising method for further research and utilization in lab-on-chip systems. PMID- 28990615 TI - A series of anionic host coordination polymers based on azoxybenzene carboxylate: structures, luminescence and magnetic properties. AB - A series of coordination polymers {[Ln(aobtc)(H2O)4].Hbipy.H2O}n (H4aobtc = azoxybenzene-2,2',3,3'-tetracarboxylic acid, bipy = 4,4'-bipyridine, and Ln = Sm(1), Eu(2), Gd(3), Tb(4), Dy(5), Er(6)) have been synthesized and characterized systematically. The cationic Hbipy+ guest incorporated polymers are isostructural sets, featuring a one-dimensional (1D) zigzag double chain edifice composed of binuclear clusters [Ln2(H4aobtc)2], with the Hbipy+ guest being located on two sides. These 1D chains are further interlinked into a 2D layer structure, and further extended into a 3D framework through hydrogen bonding interactions. The luminescence emission spectra of polymers 2 and 3 are based on the H4aobtc acid ligands, while 1 and 4 display the characteristic f-f transitions of Ln(iii) ions. Magnetic measurements revealed the presence of ferromagnetic behavior in polymer 3. The magnetic behaviors of 4 and 6 are ascribed to the depopulation of the Stark levels and/or weak antiferromagnetic interactions within MOFs at lower temperature. Slow relaxation is observed through the alternating-current susceptibility measurements for 5 at lower temperature, and the coexistence of weak ferromagnetism corresponding to the spin-canting-like behavior. PMID- 28990616 TI - Complexation of beta-cyclodextrin with dual molecular probes bearing fluorescent and paramagnetic moieties linked by short polyether chains. AB - Electron paramagnetic resonance (EPR) and fluorescence spectroscopies provide molecular-level insights on the interaction of paramagnetic and fluorescent species with the microenvironment. A series of dual molecular probes bearing fluorescent and paramagnetic moieties linked by flexible short polyether chains have been synthesized. These new molecular probes open the possibility to investigate various multi-component systems such as host-guest systems, polymeric micelles, gels and protein solutions by using EPR and fluorescence spectroscopies concertedly. The EPR and fluorescence spectra of these compounds show that the dependence of the rotational correlation time and fluorescence quantum yield on the chain length of the linker is not linear, due to the flexibility of the polyether linker. The quenching effect of the nitroxide moiety on the fluorescence intensity of the pyrene group varies with the linker length and flexibility. The interaction of these dual molecular probes with beta cyclodextrin, in solution and in polymeric gels, was evaluated and demonstrated by analysis of EPR and fluorescence spectra. PMID- 28990618 TI - Direct crystallographic evidence of the reversible photo-formation and thermo rupture of a coordination bond inducing spin-crossover phenomenon. AB - A detailed crystallographic study of [FeII(LN5)(CN)2].MeOH (LN5 = 2,13-dimethyl 3,6,9,12,18-pentaazabicyclo[12.3.1]octadeca-1(18),2,12,14,16-pentaene) shows the light-induced formation and thermally-assisted rupture of a metal-ligand coordination bond concomitantly with a spin-crossover process occurring at the Fe(ii) center between its low spin (LS) and high spin (HS) states. These results illustrate the remarkable reversibility and non-destructive character of this photo-induced magneto-structural process in a single crystal. PMID- 28990619 TI - Exploring the tunable excitation of QDs to maximize the overlap with the absorber for inner filter effect-based phosphorescence sensing of alkaline phosphatase. AB - The inner filter effect (IFE) is an effective way for fluorescence modulation and thus has been extensively explored for the development of fluorescence assays. Theoretically, the key to maximize the sensitivity of IFE-based fluorescence assays is to enlarge the overlap between the absorption of the absorber and the excitation/emission of the fluorophore. Therefore, in this work, the tunable excitation of quantum dots (QDs) was explored for screening of the IFE pair having the best IFE-based assay sensitivity. A series of QDs, including CdTe QDs with different sizes, carbon dots, Cu-doped CdS QDs, and Mn-doped ZnS QDs, were investigated. PNPP (p-nitrophenylphosphate) was chosen as the absorber since its absorption overlapped with the above QDs. Besides, it can be catalytically converted to p-nitrophenol (PNP) by alkaline phosphatase (ALP) together with an absorption spectrum change (red-shift). Interestingly, it was found that the IFE efficiency of different PNPP-QD pairs increased almost linearly with the corresponding spectral overlap, and Mn-doped ZnS QDs were eventually chosen for the IFE assay of ALP because of the maximum spectral overlap and thus the best sensitivity. A simple and sensitive turn-on phosphorescence ALP assay was developed, with a detection limit of 4 * 10-4 U L-1. Because of the high sensitivity, we also found that ALP of different origins possessed different enzymatic activities. The developed ALP phosphorescence assay was successfully employed for the analysis of ALP in serum samples. PMID- 28990620 TI - Single Ni sites distributed on N-doped carbon for selective hydrogenation of acetylene. AB - We prepared single Ni atoms embedded in an N-doped carbon catalyst with the assistance of metal organic frameworks. The dispersion of Ni atoms was verified by taking X-ray absorption fine structure measurements. Under the typical conditions for hydrogenation of acetylene, this single-site heterogeneous catalyst showed great potential as an alternative to Pd-based materials. PMID- 28990621 TI - Carbon oxidation reactions could misguide the evaluation of carbon black-based oxygen-evolution electrocatalysts. AB - A variety of carbon-based materials have been reported as electrocatalysts towards the oxygen evolution reaction. However, carbon oxidation during the OER was rarely considered or even neglected in most of the reports. Herein, using carbon black as a model material, we develop a method to estimate the contribution of carbon oxidation reactions (CORs) to the measured current during the OER test. It is shown that the CORs could result in significant overestimation of the OER activity of carbon black-based electrocatalysts. PMID- 28990622 TI - Cooperative self-assembly and gelation of organogold(i) complexes via hydrogen bonding and aurophilic AuAu interactions. AB - With the synergistic combination of intermolecular Au(i)-Au(i) and hydrogen bonding interactions, a rod-coil alkynyl-gold(i)-isocyanide monomer tends to form supramolecular fibers and gels via a cooperative nucleation-elongation self assembly mechanism, which display Ag(i) ion-triggered responsiveness. PMID- 28990623 TI - Friction controls even submerged granular flows. AB - We investigate the coupling between the interstitial medium and granular particles by studying the hopper flow of dry and submerged systems experimentally and numerically. In accordance with earlier studies, we find that the dry hopper empties at a constant rate. However, in the submerged system we observe the surging of the flow rate. We model both systems using the discrete element method, which we couple with computational fluid dynamics in the case of a submerged hopper. We are able to match the simulations and the experiments with good accuracy by fitting the particle-particle contact friction for each system separately. Submerging the hopper changes the particle-particle contact friction from MUvacuum = 0.15 to MUsub = 0.13, while all the other simulation parameters remain the same. PMID- 28990624 TI - A copper-catalyzed tandem reaction for the construction of coumarin fused 9H pyrrolo[1,2-a]indoles. AB - An efficient copper-catalyzed Friedel-Crafts alkylation/cyclization/isomerization sequence of 3-arylcarbonyl coumarins and 3-methyl indole was developed to afford a wide range of functionalized coumarin fused 9H-pyrrolo[1,2-a]indoles, which feature a 6-6-5-5-6 pentacyclic core, in 34-99% yields. Moreover, gram-scale experiment and chemical transformations were conducted to demonstrate the synthetic value of this protocol. PMID- 28990625 TI - Enantioselective organocatalytic Michael additions of N,N'-dialkylbarbituric acids to enones. AB - N,N'-Dialkylbarbituric acids as cyclic malonamide donors were successfully used in the enantioselective Michael addition reaction of enones. Using cinchona alkaloid-based bifunctional squaramide as an organocatalyst, this Michael reaction of N,N'-di-tert-butylbarbituric acid with various enones features a highly enantioselective (91-99% ee) production of the corresponding optically active 5-substituted barbituric acid derivatives. The transformations of the Michael product for the barbituric acid structural unit were realized in two ways, deprotection to remove the N-tert-butyl group and alkylation to produce 5,5 disubstituted barbituric acid derivatives. PMID- 28990627 TI - Controlling the generation of bilayer and multilayer vesicles in block copolymer/epoxy blends by a slow photopolymerization process. AB - Vesicles are a highly attractive morphology to achieve in micellar dispersions of block copolymers (BCP) in epoxy thermosets due to the fact that small amounts can affect a large volume fraction of the matrix, a fact that is important for toughening purposes. However, generating vesicles in epoxy matrices requires operating in a narrow range of formulations and processing conditions. In this report, we show that block-copolymer vesicles dispersed in an epoxy matrix could be obtained through a sphere-to-cylinder-to-vesicle micellar transition induced by visible-light photopolymerization at room temperature. A 10 wt% colloidal solution of poly(ethylene-co-butene)-block-poly(ethylene oxide) (PEB-b-PEO) block copolymer (BCP) in an epoxy monomer (DGEBA) self-assembled into spherical micelles as shown by small-angle X-ray scattering (SAXS). During a slow photopolymerization of the epoxy monomer carried out at room temperature, a sphere-to-cylinder-to-vesicle transition took place as revealed by in situ SAXS and TEM images. This was driven by the tendency of the system to reduce the local interfacial curvature as a response to a decrease in the miscibility of PEO blocks in the polymerizing epoxy matrix. When the BCP concentration was increased from 10 to 20 and 40 wt%, the final structure evolved from bilayer vesicles to multilayer vesicles and to lamellae, respectively. In particular, for 20 wt% PEB b-PEO, transient structures such as partially fused multilayered vesicles were observed by TEM, giving insight into the growth mechanism of multilayer vesicles. On the contrary, when a relatively fast thermal polymerization was performed at 80 degrees C, the final morphology consisted of kinetically trapped spherical and cylindrical micelles. Hopefully, this study will lead to new protocols for the preparation of vesicles dispersed in epoxy matrices in a controlled way. PMID- 28990628 TI - Computational identification of protein S-sulfenylation sites by incorporating the multiple sequence features information. AB - Cysteine S-sulfenylation is a major type of posttranslational modification that contributes to protein structure and function regulation in many cellular processes. Experimental identification of S-sulfenylation sites is challenging, due to the low abundance of proteins and the inefficient experimental methods. Computational identification of S-sulfenylation sites is an alternative strategy to annotate the S-sulfenylated proteome. In this study, a novel computational predictor SulCysSite was developed for accurate prediction of S-sulfenylation sites based on multiple sequence features, including amino acid index properties, binary amino acid codes, position specific scoring matrix, and compositions of profile-based amino acids. To learn the prediction model of SulCysSite, a random forest classifier was applied. The final SulCysSite achieved an AUC value of 0.819 in a 10-fold cross-validation test. It also exhibited higher performance than other existing computational predictors. In addition, the hidden and complex mechanisms were extracted from the predictive model of SulCysSite to investigate the understandable rules (i.e. feature combination) of S-sulfenylation sites. The SulCysSite is a useful computational resource for prediction of S-sulfenylation sites. The online interface and datasets are publicly available at . PMID- 28990629 TI - The electrochemical effect of various Si/Zr molar ratios on anode materials in lithium-ion batteries. AB - The aim of this study was to unveil the mechanisms of SiO2/ZrO2 (SSZ) anode materials through electrochemical analysis and to understand the effect of various Si/Zr molar ratios (Si/Zr = 0.5, 1, and 2) on the performance of SSZ anode materials with these mechanisms. The 2-SSZ (Si/Zr = 2) electrode had a much higher capacity than that of the 0.5- or 1-SSZ (Si/Zr = 0.5 or 1) electrode. It exhibited superior cycling performance when compared to commercial graphite (theoretical capacity of 372 mA h g-1). The 2-SSZ had a capacity of 461 mA h g-1 at a high current density of 100 mA g-1 over 30 cycles. These characteristics are due to the effects from each of the different reversible materials formed by the SSZs. Zr2Si and Zr5Si3, ZrSi, or ZrSi2 were formed by the 0.5-, 1-, and 2-SSZs, respectively, which would affect the reversible storage capacity. ZrSi2 provided an increase in the possible reaction area for the guest species (lithium ions) at the empty interstitial site in the host materials as well as a large area for accommodating a volume change. It was supportive by maintaining the lattice constant and reducing the ratio of the structure distortion. Furthermore, the 2 SSZ structure consisted of an overall amorphous structure with a crystalline structure related to the Zr-O-Si bond unlike the 0.5- and 1-SSZs which had an overall crystalline structure. Such a combined structure of 2-SSZ was advantageous for providing good capacity due to the amorphous structure and an efficient pathway for electron transport and little pulverization due to the crystalline structure. This structure led to its superior performance and long lifespan. PMID- 28990630 TI - Synergistic effect of polymer encapsulated silver nanoparticle doped WS2 sheets for plasmon enhanced 2D/3D heterojunction photodetectors. AB - Chemical doping and plasmonic enhanced photoresponsivity of two dimensional (2D) n-WS2/p-Si heterojunctions are demonstrated for the first time. Novel PVP coated Ag0 intercalation induced synthesis has led to the formation of impurity-free, chemically doped few-layer n-WS2 with reversed conductivity following the Maxwell Wagner-Sillars interfacial effect. The resultant composite film exhibits excellent stability and tunable plasmonic absorption due to silver nanoparticles of different sizes. A sharp band-edge absorption of the hybrid material indicates the presence of spin-orbit coupled direct band gap transitions in WS2 layers, in addition to a broader plasmonic peak attributed to Ag nanoparticles. Stabilized Ag-nanoparticle (~4-6 nm) embedded electron rich n-WS2 has been used to fabricate plasmon enhanced, silicon compatible heterojunction photodetectors. The detectors exhibited superior properties, possessing a photo-to-dark current ratio of ~103, a very high responsivity (8.0 A W-1) and an EQE of 2000% under 10 V bias with a broad spectral photoresponse in the wavelength range of 400-1100 nm. The results provide a new paradigm for intercalant impurity-free metal nanoparticle assisted exfoliation of n-type few-layer WS2, with the nanoparticles playing a dual role towards the realization of 2D materials based broadband heterojunction optoelectronic devices by inducing chemical doping as well as tunable plasmon enhanced absorption. PMID- 28990632 TI - The use of RGD-engineered exosomes for enhanced targeting ability and synergistic therapy toward angiogenesis. AB - Promoted therapeutic angiogenesis is a major objective in the area of regenerative medicine, and sufficient vascularization of artificial tissues or organs is one of the main difficulties for the realization of tissue engineering methods. The identification of new kinds of pro-angiogenic materials will greatly profit developments in regenerative medicine. The use of exosomes for this intention is a considerably new idea developed in recent years. However, several limitations need to be addressed before their use as clinical therapeutics, including the lack of efficient exosome enrichment and methods to endow exosomes with targeting ability. Herein, we pioneered biomimetic particles with topographic structures for exosome isolation. Using this system, nearly 80% of exosomes were isolated in 30 min. Through a donor cell-assisted membrane modification strategy, the isolated exosomes exhibited increased targeting to blood vessels due to the modified Arg-Gly-Asp (RGD) peptide on the exosome membrane, and simultaneously possessed a synergistic therapeutic angiogenesis effect and angiogenesis imaging attributed to metabolic labeling by click chemistry both in vitro and in vivo. The engineered exosomes represent a potential new therapeutic tool for angiogenesis therapy and imaging in a bio friendly manner. PMID- 28990631 TI - A chemosensor for micro- to nano-molar detection of Ag+ and Hg2+ ions in pure aqueous media and its applications in cell imaging. AB - The pyridine substituted thiourea derivative PTB-1 was synthesized and characterized by spectroscopic techniques as well as by single crystal X-ray crystallography. The metal ion sensing ability of PTB-1 was explored by various experimental (naked-eye, UV-Vis, fluorescence, mass spectrometry and 1H NMR spectroscopy) and theoretical (B3LYP/6-31G**/LANL2DZ) methods. PTB-1 exhibited a highly selective naked-eye detectable color change from colorless to dark brown and UV-Vis spectral changes for the detection of Ag+ with a detection limit of 3.67 MUM in aqueous medium. The detection of Ag+ ions was achieved by test paper strip and supported silica methods. In contrast, PTB-1 exhibited a 23-fold enhanced emission at 420 nm in the presence of Hg2+ ions with a nano-molar detection limit of 0.69 nM. Finally, the sensor PTB-1 was applied successfully for the intracellular detection of Hg2+ ions in a HepG2 liver cell line, which was monitored by the use of confocal imaging techniques. PMID- 28990633 TI - A Tailor-Made Exercise Program for Improving Balance and Mobility in Older Adults With Type 2 Diabetes. AB - Effectiveness of an exercise program designed for improving postural control and mobility in older adults with type 2 diabetes was investigated. Ninety-three adults 65 or older diagnosed with type 2 diabetes and able to walk unaided were recruited. The intervention group received exercise training focused on ankle strengthening and mobility twice per week for 10 weeks. The control group did not participate in any exercise program. After 10 weeks, the intervention group showed significantly greater improvement in the mean Sensory Organization Test composite score (4.4 vs. 0.3; p = 0.01) as well as visual ratio (0.1 vs. 0.002; p = 0.01) and vestibular ratio (0.1 vs. 0.003; p < 0.001) than the control group after adjusting for covariates. A greater trend of improvement in the Timed Up and Go and Single-Leg Stance Test was also found in the intervention group. Exercise training focusing on the ankle is effective in enhancing the postural stability of older adults with type 2 diabetes and can potentially be effective in improving single-leg standing balance and mobility. [Journal of Gerontological Nursing, 44(2), 41-48.]. PMID- 28990635 TI - Nurses' Communication of Safety Events to Nursing Home Residents and Families. AB - Although communication is an essential part of the nursing process, nurses have little to no formal education in how to best communicate patient safety event (PSE) information to nursing home (NH) residents and their family members. The current mixed-methods study tested an intervention aimed at educating nurses on how to communicate a PSE to residents/family members using a structured communication tool. Nurse participants improved their knowledge of PSE communication, especially about the cause of the event, what they would say to the resident/family member, and future prevention of the PSE. Through qualitative subgroup analysis, an increased number of empathic statements were noted post intervention. The tool tested in this study provides structure to an important care process that is necessary for improving the culture of safety in NH settings. [Journal of Gerontological Nursing, 44(2), 25-32.]. PMID- 28990634 TI - Understanding End-of-Life Decision-Making Terminology Among African American Older Adults. AB - The purpose of the current study was to examine understanding of end-of-life (EOL) decision-making terminology among family caregivers of African American older adults with dementia. This qualitative descriptive study was part of a larger mixed-methods study from which a subset of caregivers (n = 18) completed interviews. Data were analyzed using descriptive statistics and content analyses guided by methods of qualitative analysis. Caregiver interpretation of EOL decision-making terminology varied between associations before and/or after death. EOL decision making was most often a family decision, based on past experiences, and included reliance on resources such as faith or spirituality and health care providers. Patients and families attach meaning to health care terms that should be aligned with health care providers' understanding of those terms. Results provide insight to improve EOL decision making in this population via tailored interventions for patients, families, and health care providers. [Journal of Gerontological Nursing, 44(2), 33-40.]. PMID- 28990636 TI - Preferences for Everyday Living: Understanding the Impact of Cognitive Status on Preference Importance Ratings in Nursing Homes. AB - Assessing everyday living preferences for nursing home residents is a cornerstone of delivering person-centered care (PCC), yet little is known about how cognitive ability can influence the importance of reported preferences. The current study examined the effect of cognitive ability on the level and stability of reported importance of preferences for everyday living in a sample of 255 nursing home residents across 3 months. Participants were grouped by cognitive impairment status (none-to-low, mild, and moderate) at baseline and completed the Preferences for Everyday Living Inventory, Nursing Home version interview at baseline and 3 months. Repeated measures analyses of covariance revealed no significant differences (p > 0.001) between cognitive groups on their reported level of importance of preferences at baseline and no significant change over 3 months. These data highlight the value of assessing everyday care preferences to help support delivery of PCC for individuals with and without cognitive impairment. [Journal of Gerontological Nursing, 44(5), 9-17.]. PMID- 28990637 TI - Qualitative Study of Depression Literacy Among Korean American Parents of Adolescents. AB - Lack of depression literacy is associated with low help-seeking behaviors for mental health care in adolescents. As parents generally determine adolescents' health care, ensuring parents can recognize depressive symptoms is crucial. The current study explored depression literacy among Korean American parents of adolescents ages 12 to 19 using a qualitative descriptive design. Semantic content analysis was performed using data from three focus group interviews conducted in 2015 with Korean American parents (10 mothers, four fathers) of adolescents. Participants lacked knowledge about the biological causes and medicinal treatment of depression. Most believed that depression cannot be fully treated, relapses occur easily, and medication is taken indefinitely. Gender influenced perceptions of symptoms. Parents often overlooked children's depressive symptoms until schools alerted them. Nursing interventions should educate parents about the biological causes of depression, strategies for addressing adolescents' symptoms, community-based professional resources, and success stories about depression treatment. [Journal of Psychosocial Nursing and Mental Health Services, 56(1), 48-56.]. PMID- 28990638 TI - Emotional and Psychosocial Problems Encountered by Children Who Have Been Sexually Abused. AB - The current descriptive analysis sought to identify the emotional and psychosocial problems experienced by children who have been sexually abused. Of 518 children with a history of sexual abuse who applied to the Child Protection Center, 443 were included in the study. Approximately 71.6% of children were subject to sexual abuse entailing penetration, whereas 69% were subject to sexual abuse not entailing penetration. After-effects reported included despair (46.5%), fear of reoccurrence of the incident (52.8%), distrust of others (36.8%), difficulty sleeping (32.7%), negative expectations about the future (32.1%), and self-blame (31.1%). Nurses have crucial roles and functions in the protection, improvement, treatment, and rehabilitation of the health of children who have been sexually abused. [Journal of Psychosocial Nursing and Mental Health Services, 56(2), 37-43.]. PMID- 28990639 TI - Pharmacogenomics and Psychiatric Clinical Care. AB - Approximately one in five individuals in the United States experiences mental health issues in any given year, and these disorders are consistently among the leading causes of years lived with disability. Unfortunately, many mental illnesses are lifelong conditions that require medication and therapy to improve quality of life, yet clinical trial data show that many patients fail to achieve remission or require several pharmacological interventions prior to remission. These results indicate a need to address the variability among patients in their response to medication, in addition to developing treatment plans tailored to the individual. One approach that may help explain patient variability in response to medication is pharmacogenetic testing. The current review shows the clinical use of pharmacogenetic testing in a small subset of gene variants and how they pertain to psychiatric illness and treatment. Recent evidence suggests that genetic testing for psychiatric illness can improve patient outcomes in addition to decreasing health care costs. [Journal of Psychosocial Nursing and Mental Health Services, 56(1), 22-31.]. PMID- 28990640 TI - Very Late-Onset Schizophrenia-Like Psychosis: A Clinical Update. AB - Psychosis symptoms (delusions and hallucinations) are multifactorial in origin and, in later life, occur in the context of schizophrenia, delirium, dementia, delusional and schizophrenia-like disorders, mood disorders, and alcohol or substance abuse. The current article provides a clinical overview of very late onset (after age 60) schizophrenia-like psychosis (VLOSLP), summarizing the literature on treatment options and reflecting on the role of psychiatric-mental health nurses (PMHNs). Increased awareness of the clinical presentation, key features, and evidence-based treatment options will assist PMHNs to confidently recognize this often under-diagnosed disorder and adopt a more assertive role in terms of engagement and follow up. Pragmatic research involving individuals with VLOSLP is required to increase the evidence base for treatment and improve outcomes of care. [Journal of Psychosocial Nursing and Mental Health Services, 56(1), 37-47.]. PMID- 28990641 TI - Dignity in Older Adults With Schizophrenia Residing in Assisted Living Facilities. AB - There is a lack of nursing literature on older adults' perceptions of dignity, specifically those of older adults with schizophrenia. With the aging population, mental health services and support for older adults with schizophrenia will become a greater priority. The purpose of the current descriptive phenomenological study was to describe the meaning of the lived experience of dignity for older adults with schizophrenia residing in assisted living facilities. A purposive sample of eight older adults with schizophrenia residing in assisted living facilities participated in semi-structured interviews following the descriptive phenomenological psychological method. Five intertwined constituents were identified: (1) dignity is an intrinsic or self-regarding experience; (2) dignity is an experience that is reciprocal, extrinsic, and regards others, and is embedded in social relationships; (3) dignity can be eroded by ageism, stigma, discrimination, and alienation; (4) dignity can be interrupted when positive and negative symptoms of schizophrenia are present and misunderstood by others; and (5) dignity can be enhanced when oneself and others embrace a recovery-focused relationship. Implications for mental health nursing are provided. [Journal of Psychosocial Nursing and Mental Health Services, 56(2), 20-28.]. PMID- 28990642 TI - Quantitative phase microscopy for evaluation of intestinal inflammation and wound healing utilizing label-free biophysical markers. AB - Inflammatory bowel diseases (IBD) are inflammatory disorders of the gastrointestinal tract characterized by a chronic relapsing disease course. As uncontrolled intestinal inflammation can result in severe disease complications, recent treatment targets of IBD evolved toward seeking the absence of mucosal and histological inflammation. However, this approach requires adequate histological evaluation of IBD disease activity. The diagnostic challenge of histological examination of intestinal inflammation is documented by the multitude of proposed histological scoring systems. In this context, we review quantitative phase imaging (QPI) techniques such as digital holographic microscopy (DHM) for characterizing intestinal inflammation. DHM determines optical path-length delays in a stain-free manner, thereby providing the tissue refractive index as a biophysical marker that directly correlates to tissue density. Recently, DHM has been successfully applied in cell biology, cancer cell research and infectious induced cellular alterations. We summarized the capabilities of DHM and related QPI techniques to assess the severity of intestinal inflammation in experimental colitis as well as in colonic samples from human IBD patients. Moreover, we illustrate major advantages of DHM facilitated multimodal evaluation of epithelial wound healing processes as assessed by physical parameters like cell volume, density, thickness and dry mass in vitro. Furthermore, potential limitations of DHM and future utilities of QPI are discussed. In conclusion, DHM represents a promising, easy-to-use quantitative tool to provide accurate and objective assessment of intestinal inflammation and may pave the way towards automated label-free digital pathology and related in vitro cell culture analysis in future. PMID- 28990643 TI - [Commercial video games in the rehabilitation of patients with sub-acute stroke: a pilot study]. AB - INTRODUCTION: Stroke generates dependence on the patients due to the various impairments associated. The use of low-cost technologies for neurological rehabilitation may be beneficial for the treatment of these patients. AIM: To determine whether combined treatment using a semi-immersive virtual reality protocol to an interdisciplinary rehabilitation approach, improve balance and postural control, functional independence, quality of life, motivation, self esteem and adherence to intervention in stroke patients in subacute stage. PATIENTS AND METHODS: A longitudinal prospective study with pre and post intervention evaluation was carried out. Fourteen were recruited at La Fuenfria Hospital (Spain) and completed the intervention. Experimental intervention was performed during eight weeks in combination with conventional treatment of physiotherapy and occupational therapy. Each session was increased in time and intensity, using commercial video games linked to Xbox 360 degrees videoconsole and Kinect sensor. RESULTS: There were statistical significant improvements in modified Rankin scale (p = 0.04), baropodometry (load distribution, p = 0.03; support surface, p = 0.01), Barthel Index (p = 0.01), EQ-5D Questionnaire (p = 0.01), motivation (p = 0.02), self-esteem (p = 0.01) and adherence to the intervention (p = 0.02). CONCLUSIONS: An interdisciplinary rehabilitation approach supplemented with semi-immersive virtual reality seems to be useful for improving balance and postural control, functional independence in basic activities of daily living, quality of life, as well as motivation and self esteem, with excellent adherence. This intervention modality could be adopted as a therapeutic tool in neurological rehabilitation of stroke patients in subacute stage. PMID- 28990644 TI - [Relationship between homocysteinaemia and sympathetic skin response in Parkinson's disease]. AB - INTRODUCTION: High levels of homocysteine linked to treatment with levodopa have been observed in patients with Parkinsons disease (PD). Our aim was to assess the influence of serum homocysteine levels and other PD-related on the sympathetic skin response. PATIENTS AND METHODS: An observational, cross-sectional study was conducted that consecutively included patients with PD. We unilaterally assessed the sympathetic skin response in the upper limbs. We measured the influence of PD severity (measured by the Hoehn and Yahr and the Schwab and England scales, and the Unified Parkinson Disease Rating Scale) and blood homocysteine, vitamin B12 and folic acid levels on the latency and amplitude of the sympathetic skin response. RESULTS: A total of 78 patients were enrolled, and all achieved a sympathetic skin response. In the bivariate analysis, latency was significantly correlated with age, age at PD onset and homocysteinaemia levels. The presence of hyper-homocysteinemia was associated with a longer latency. The amplitude was only correlated with the score on the Schwab and England scale. In the multivariate analysis, age was the only variable that showed a significant association with the latency duration and homocysteine levels. CONCLUSION: A direct association could not be established between the increase in homocysteinaemia levels and sympathetic skin response dysfunction in PD. The results of the multivariate analysis suggest that latency prolongation in elderly patients could be due to the fact that these patients have higher blood levels of homocysteinaemia. PMID- 28990645 TI - [Transcranial direct current stimulation for the treatment of fibromyalgia: a systematic review]. AB - INTRODUCTION: Fibromyalgia is a multisymptomatic diffuse chronic musculoskeletal pain syndrome with evidence of central nervous system dysfunction. Accordingly, non-invasive brain stimulation techniques such as transcranial direct current stimulation (tDCS) may be a complementary therapeutic resource to reduce pain perception. AIMS: To review the potential effectiveness of tDCS to reduce pain in fibromyalgia, to identify the most effective neurostimulation parameters and to delimit its safety. PATIENTS AND METHODS: Systematic review of prospective studies reported in PubMed and Cochrane reviews. RESULTS: The anodal tDCS of the left primary motor cortex, at 2mA for 20 minutes with 35 cm2 electrodes on five consecutive days, provides better results in reducing pain (14-59%), and improving sleep quality, with greater accentuation on the fifth day. The clinical improvement persists up to a minimum of 60 days (11-20% reduction of pain). Adverse effects are well tolerated and few. CONCLUSIONS: The experience with tDCS in fibromyalgia is still limited. However, the anodal tDCS in the left primary motor cortex can be recommended with level B (probable therapeutic efficacy) and appears to act through the modification of the sensorial processing of the pain of thalamic inhibitory circuitry. PMID- 28990646 TI - [Clinical profile and satisfaction with anticoagulated treatment in patients with non-valvular atrial fibrillation attended in Internal Medicine and Neurology departments of Spain]. AB - AIM: To determine the clinical profile, management of anticoagulant treatment and satisfaction related to anticoagulation in outpatients with nonvalvular atrial fibrillation attended in Neurology or Internal Medicine departments of Spain. PATIENTS AND METHODS: Cross-sectional and multicenter study, in which 1,337 outpatients were included. Patients fulfilled ACTS, SAT-Q and EQ-5D questionnaires. RESULTS: 865 patients (64.7%) were recruited from Neurology department and 472 (35.3%) from Internal Medicine department. Those patients attended in Internal Medicine department were older and had more frequently hypertension, diabetes, heart failure, renal insufficiency and peripheral artery disease. Those patients attended in Neurology department had more commonly prior stroke. Overall, CHADS2 score was 3.2 +/- 1.3, CHA2DS2-Vasc 4.8 +/- 1.5 and HAS BLED 2.0 +/- 0.9. All scores were higher in those patients attended in Neurology department. Globally, 56.1% of patients were taking vitamin K antagonists, more commonly in Internal Medicine department. The adequate percent of time in therapeutic range was 47% (Rosendaal), without significant differences between groups. Satisfaction with oral anticoagulation was high in both groups, but higher in those attended in Neurology department, and higher in those individuals taking direct oral anticoagulants compared with vitamin K antagonists. CONCLUSIONS: Although there were some differences in the clinical profile of patients with atrial fibrillation attended in Neurology or Internal Medicine departments, all of them had many comorbidities and a high thromboembolic risk. Despite INR control was poor, the most common oral anticoagulant used were vitamin K antagonists. Satisfaction related to oral anticoagulation was high. PMID- 28990647 TI - [Medullar thoracic compression by tophaceous gout: presentation of a case and review of the literature]. AB - INTRODUCTION: Spine involvement in gout is an extremely uncommon complication. Dorsalgia and quadriplegia are some manifestations that may occur, although these symptoms are seen more frequently in other more prevalent pathologies, such as spinal tumors. CASE REPORT: We present an unusual case of thoracic spinal cord compression at T10-T11 level caused by the extradural deposit of tophaceous material in a 52-year-old woman with uncontrolled chronic tophaceous gout. In addition to intensive medical treatment, the patient required surgery (hemilaminectomy and spinal decompression) and subsequent rehabilitation. Overall and neurological evolution were satisfactory. PMID- 28990648 TI - [Patients organizations and new drug approval in the US. Eteplirsen and Duchenne muscular dystrophy case]. AB - INTRODUCTION: In 2016 the US Food and Drug Administration (FDA) granted the marketing authorization for eteplirsen for Duchenne muscular dystrophy. This has been a very controversial decision since it happened after a negative assessment from both the Advisory Committee and the technical FDA evaluation team. The FDA's Center for Drug Evaluation and Research (CDER) director was who ultimately approved the product, while the FDA Commissioner did not overrule that decision. AIM: To report about the most relevant events regarding the approval of eteplirsen by the US FDA. DEVELOPMENT: All relevant facts that occurred during the clinical development and evaluation phase following 'accelerated approval' procedure of eteplirsen are discussed in detail. The technical FDA evaluation team reasons supporting that the drug has not proven clinical benefit, the attitude of patient advocacy groups and the post-approval FDA requirements to the marketing authorization holder are discussed. Finally, we reflect on what is the situation Spanish patients face once eteplirsen is on the US market. CONCLUSIONS: This is a unique case in the history of drug authorizations in western countries, that shows the difficulties that current regulations on accelerated approval of new medicines could have when interpreting scarce and low quality clinical development data, when dealing with rare diseases with no available therapies. PMID- 28990649 TI - [Not Available]. PMID- 28990650 TI - [Not Available]. PMID- 28990651 TI - Randomized feasibility trial of high-intensity interval training before elective abdominal aortic aneurysm repair. AB - BACKGROUND: This study assessed the feasibility of a preoperative high-intensity interval training (HIT) programme in patients awaiting elective abdominal aortic aneurysm repair. METHODS: In this feasibility trial, participants were allocated by minimization to preoperative HIT or usual care. Patients in the HIT group were offered three exercise sessions per week for 4 weeks, and weekly maintenance sessions if surgery was delayed. Feasibility and acceptability outcomes were: rates of screening, eligibility, recruitment, retention, outcome completion, adverse events and adherence to exercise. Data on exercise enjoyment (Physical Activity Enjoyment Scale, PACES), cardiorespiratory fitness (anaerobic threshold and peak oxygen uptake), quality of life, postoperative morbidity and mortality, duration of hospital stay and healthcare utilization were also collected. RESULTS: Twenty-seven patients were allocated to HIT and 26 to usual care (controls). Screening, eligibility, recruitment, retention and outcome completion rates were 100 per cent (556 of 556), 43.2 per cent (240 of 556), 22.1 per cent (53 of 240), 91 per cent (48 of 53) and 79-92 per cent respectively. The overall exercise session attendance rate was 75.8 per cent (276 of 364), and the mean(s.d.) PACES score after the programme was 98(19) ('enjoyable'); however, the intensity of exercise was generally lower than intended. The mean anaerobic threshold after exercise training (adjusted for baseline score and minimization variables) was 11.7 ml per kg per min in the exercise group and 11.4 ml per kg per min in controls (difference 0.3 (95 per cent c.i. -0.4 to 1.1) ml per kg per min). There were trivial-to-small differences in postoperative clinical and patient-reported outcomes between the exercise and control groups. CONCLUSION: Despite the intensity of exercise being generally lower than intended, the findings support the feasibility and acceptability of both preoperative HIT and the trial procedures. A definitive trial is warranted. Registration number: ISRCTN09433624 ( https://www.isrctn.com/). PMID- 28990653 TI - Mechanism of in-vitro inhibition of UGT1A1 by paritaprevir. AB - OBJECTIVES: The direct-acting protease inhibitor paritaprevir is a new pharmaco logic option available for treatment of chronic hepatitis C (HCV). Paritaprevir is reported to inhibit human UGT 1A1, but the mechanism of inhibition and its possible clinical consequences are not established. Our objective was to evaluate the in-vitro metabolic interaction between paritaprevir and the oral contraceptive steroid ethinyl estradiol (EE), a UGT 1A1 substrate. METHODS: Enzyme kinetic parameters were determined using human liver microsomes for the biotransformation of EE to its glucuronide metabolites, and the potency and mechanism of inhibition by paritaprevir. Probenecid was used as a reference inhibitor for purposes of assay validation. KEY FINDINGS: The underlying pattern of EE kinetics was complex, with evidence of substrate inhibition. The in-vitro inhibition constant (Ki ) value for paritaprevir vs EE on average was 20 MUm and was consistent with a competitive inhibition mechanism. The ratio of in-vivo maximum plasma concentration of paritaprevir to in-vitro Ki was <0.1. CONCLUSIONS: Paritaprevir is an in-vitro inhibitor of UGT 1A1. However, the in vitro Ki value relative to maximum clinical plasma concentrations is below the threshold to trigger a recommendation for pharmacokinetic drug interaction studies. PMID- 28990652 TI - Bronchiectasis and deteriorating lung function in agammaglobulinaemia despite immunoglobulin replacement therapy. AB - Immunoglobulin replacement therapy enhances survival and reduces infection risk in patients with agammaglobulinaemia. We hypothesized that despite regular immunoglobulin therapy, some patients will experience ongoing respiratory infections and develop progressive bronchiectasis with deteriorating lung function. One hundred and thirty-nine (70%) of 199 patients aged 1-80 years from nine cities in the United Kingdom with agammaglobulinaemia currently listed on the UK Primary Immune Deficiency (UKPID) registry were recruited into this retrospective case study and their clinical and laboratory features analysed; 94% were male, 78% of whom had Bruton tyrosine kinase (BTK) gene mutations. All patients were on immunoglobulin replacement therapy and 52% had commenced therapy by the time they were 2 years old. Sixty per cent were also taking prophylactic oral antibiotics; 56% of patients had radiological evidence of bronchiectasis, which developed between the ages of 7 and 45 years. Multivariate analysis showed that three factors were associated significantly with bronchiectasis: reaching 18 years old [relative risk (RR) = 14.2, 95% confidence interval (CI) = 2.7-74.6], history of pneumonia (RR = 3.9, 95% CI = 1.1-13.8) and intravenous immunoglobulin (IVIG) rather than subcutaneous immunoglobulin (SCIG) = (RR = 3.5, 95% CI = 1.2 10.1), while starting immunoglobulin replacement after reaching 2 years of age, gender and recent serum IgG concentration were not associated significantly. Independent of age, patients with bronchiectasis had significantly poorer lung function [predicted forced expiratory volume in 1 s 74% (50-91)] than those without this complication [92% (84-101)] (P < 0.001). We conclude that despite immunoglobulin replacement therapy, many patients with agammaglobulinaemia can develop chronic lung disease and progressive impairment of lung function. PMID- 28990654 TI - Analysis of volatiles in brown rice, germinated brown rice, and selenised germinated brown rice during storage at different vacuum levels. AB - BACKGROUND: The quality of nutritionally enhanced foods can be determined by evaluating changes in the volatile compounds produced in these foods over time. In this work, selenium-enriched germinated brown rice (Se-GBR), germinated brown rice (GBR), and brown rice (BR) stored under 90% relative humidity, 38 degrees C, and various vacuum levels were investigated. The relative abundance and differences of volatile compounds in Se-GBR, GBR, and BR over various storage periods were detected. The correlation of volatile compound abundance with vacuum level and storage time was analysed using principal component analysis (PCA). RESULTS: Volatile compounds in the three samples were quantified at various storage periods (0, 90 and 150 days). Approximately 100 volatile compounds and eight species were identified and classified. Various proportions or types of volatile compounds were found in each sample at different sampling times. PCA results showed an isolation of volatile compounds in terms of sampling day and vacuum level at each storage period. CONCLUSION: Changes in volatile compounds over time and vacuum levels can provide bases for assessing of the nutritional quality of Se-GBR, GBR, and BR. (c) 2017 Society of Chemical Industry. PMID- 28990655 TI - Round window plugging in the treatment of superior semicircular canal dehiscence. AB - OBJECTIVES/HYPOTHESIS: Objectives were to describe the use of round window plugging for superior semicircular canal dehiscence syndrome and review further recommendations regarding the procedure based on our experience and to compare results with recent literature on round window plugging. STUDY DESIGN: Retrospective case series. METHODS: Fourteen patients underwent round window plugging for superior semicircular canal dehiscence at our institution from 2012 to 2015. All patients underwent the same surgical procedure. Available pre- and postoperative data were reviewed. RESULTS: Fourteen patient charts were reviewed. Symptoms of autophony improved in nine of 14 (64%) patients. Symptoms of pressure induced vertigo improved in seven of 12 (58%) patients. Hennebert's sign that was positive preoperatively only improved in one of six (17%) patients. A positive preoperative vestibular evoked myogenic potential improved in only one of six (17%) patients. Six of 13 (46%) patients had increased air conduction thresholds postoperatively. CONCLUSIONS: Round window plugging has been described as a less invasive treatment for patients with superior semicircular canal dehiscence. Although the procedure did benefit some of our patients, successful outcomes were not predictable. Improvement in at least one objective finding was seen in only 21% of the patients studied. Hennebert's sign and vestibular evoked myogenic potentials that were positive preoperatively only improved in 17% of patients. At our institution, round window plugging is no longer considered a reasonable treatment option for most patients with superior semicircular canal dehiscence. We recommend that further study on this topic follow a standardized pre- and postoperative assessment. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:1445-1452, 2018. PMID- 28990657 TI - Proper fin-clip sample collection for molecular analyses in the age of eDNA. PMID- 28990656 TI - Optimisation of saponin extraction conditions with Camellia sinensis var. assamica seed and its application for a natural detergent. AB - BACKGROUND: Camellia sinensis var. assamica seed cake (a by-product of tea-seed oil) is an abundant resource with poor utilisation. C. sinensis var. assamica seed saponin (CSS) is one kind of non-ionic surfactant. In this study, the CSS extraction conditions were optimised by response surface methodology (RSM) and then the CSS detergent was developed. Additionally, the safety and decontamination ability of the developed detergent were evaluated. RESULTS: The optimised extraction conditions were including the extracting temperature of 40.04 degrees C, extraction time of 4.97 h, ethanol concentration of 64.11% and liquid-solid ratio of 14.57:1 mL g-1 . The formula of the CSS detergent was as follows: 20% crude CSS, 0.3% oxidised tea polyphenols (OTPs), 0.2% nisin, 0.3% sodium dehydroacetate, 0.7% sodium alginate and 0.5% sodium polyacrylate. The LD50 of the CSS detergent exceeds 14 g kg-1 in mice, indicating the detergent was non-toxic. Both of the emulsifying and the pesticide residues removal abilities of the CSS detergent were significantly stronger than the commercial detergent. CONCLUSION: A natural tea seed saponin detergent with good safety and decontamination ability was successfully developed. This can make better use of the tea seed cake, thereby creating added value in the tea seed oil industry. (c) 2017 Society of Chemical Industry. PMID- 28990659 TI - Persistence of STAT-1 inhibition and induction of cytokine resistance in pancreatic beta cells treated with St John's wort and its component hyperforin. AB - OBJECTIVES: St John's wort extract (SJW) and its component hyperforin (HPF) were shown to potently inhibit cytokine-induced STAT-1 and NF-kappaB activation in pancreatic beta cells and protect them against injury. This study aimed at exploring the time course of STAT-1 inhibition afforded by these natural compounds in the beta-cell line INS-1E. METHODS: INS-1E cells were pre-incubated with SJW extract (2-5 MUg/ml) or HPF (0.5-2 MUm) and then exposed to a cytokine mixture. In some experiments, these compounds were added after or removed before cytokine exposure. STAT-1 activation was assessed by electrophoretic mobility shift assay, apoptosis by caspase-3 activity assay, mRNA gene expression by RT qPCR. KEY FINDINGS: Pre-incubation with SJW/HPF for 1-2 h exerted a remarkable STAT-1 downregulation, which was maintained upon removal of the compounds before early or delayed cytokine addition. When the protective compounds were added after cell exposure to cytokines, between 15 and 90 min, STAT-1 inhibition also occurred at a progressively decreasing extent. Upon 24-h incubation, SJW and HPF counteracted cytokine-induced beta-cell dysfunction, apoptosis and target gene expression. CONCLUSIONS: SJW and HPF confer to beta cells a state of 'cytokine resistance', which can be elicited both before and after cytokine exposure and safeguards these cells from deleterious cytokine effects. PMID- 28990658 TI - Production of probiotic bovine salami using Lactobacillus plantarum 299v as adjunct. AB - BACKGROUND: Five probiotic lactobacilli were tested, alone or in combination with two commercial starters, to select the most suitable strain for a probiotic bovine salami production. Lactobacillus plantarum 299v was used with both starters, to make salami according to a traditional recipe. Salami obtained by using just the starters and by spontaneous fermentation, served as control. Microbial dynamics, as well as the main physico-chemical parameters, were monitored throughout ripening. The survival of probiotic 299v was confirmed by strains' tracking by means of RAPD-PCR coupled to a culture-independent approach PCR-DGGE-based. RESULTS: The results showed a remarkable viability of the probiotic strain even after 60 days of storage. Experimental salami exhibited the same level of sensory acceptance of control salami, were hygienically safe, and characterised by pH, weight loss and microbiological loads within the ranges conventionally advocated for optimal fermented sausages. CONCLUSION: Outcomes indicate the workable possibility of using second-quality beef cuts for probiotic salami production. (c) 2017 Society of Chemical Industry. PMID- 28990660 TI - Relationship of stroke risk and hearing loss in African Americans: The Jackson Heart Study. AB - OBJECTIVES/HYPOTHESIS: To evaluate the relationships among measures of stroke risk and hearing in an African American cardiovascular study cohort. STUDY DESIGN: Prospective cohort study. METHODS: The relationships between stroke risk profiles and hearing of 1,107 individuals from a cohort of African Americans were assessed. Several different hearing pure-tone averages (PTAs) were constructed representing different frequency regions of hearing, namely PTA low, PTA mid, and PTA high. Stroke risk profiles were calculated using validated 10-year cardiovascular disease risk scores. Gamma regression analyses were performed for each PTA given as a continuous variable with change in stroke risk score. Logistic regression analyses, presented as odds ratios, were performed with hearing loss defined as any PTA >25 dB hearing level. Stratification models were analyzed for age quarterlies and among sex. RESULTS: Single unit increases of stroke risk percentage were found to be predictive of increases in all PTA threshold levels in gamma regression analyses for the overall pooled sample. The relationship was influenced by age, where fewer significant relationships were observed at higher ages. When analyzed with respect to stroke risk categories, using low risk as the reference group, there was found to be a significant association between stroke risk and hearing loss in the medium- and high-risk groups, with a stronger relationship in the high-risk group for all PTA threshold levels. CONCLUSIONS: This study provides evidence that stroke risk has a positive predictive relationship with hearing pure-tone threshold. LEVEL OF EVIDENCE: 2b. Laryngoscope, 128:1438-1444, 2018. PMID- 28990661 TI - Second tympanostomy tube placement in children with recurrent acute otitis media. AB - OBJECTIVES/HYPOTHESIS: To determine the rate and predictors of electing for a second bilateral myringotomy and tympanostomy tube placement (BMT) in children with recurrent acute otitis media (RAOM). STUDY DESIGN: Retrospective chart review. METHODS: Charts of 600 children who underwent BMT for RAOM between 2012 and 2014 were reviewed. RESULTS: The overall rate of a second BMT was 15.2% (91/600) and occurred a median of 1.58 years after the initial BMT. The most common indication was continued RAOM with extruded tubes. There was a higher rate of second BMT in patients of younger age (1.06 vs. 1.32 years old, P < .001) and those with a positive family history of RAOM/BMT in a first-degree relative (odds ratio [OR]: 1.67, 95% confidence interval [CI]: 1.02-2.73, P = .041). Identification of middle ear fluid intraoperatively (OR: 1.99, 95% CI: 1.22-3.26, P = .005) but not preoperatively (OR: 1.88, 95% CI: 0.98-3.57, P = .051) was associated with higher rates of second BMT. Children with bilateral intraoperative fluid (OR: 2.25, 95% CI: 1.42-3.58, P < .001) or fluid both preoperatively and intraoperatively (OR: 2.25, 95% CI: 1.40-3.61, P = .001) had greater higher risk of requiring second BMT. In this series, the finding of blocked tubes or tube otorrhea at the first postoperative visit were not predictive of an increased risk of second BMT. CONCLUSIONS: Children who underwent BMT for RAOM were more likely to undergo second BMT if they were of younger age, had a family history of RAOM/BMT, or were found to have middle ear fluid intraoperatively. The overall second BMT rate for children with RAOM is lower than in studies examining all BMT indications. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:1476-1479, 2018. PMID- 28990662 TI - The radioanatomy of endonasal flap coverage of skull base defects: A tool for preoperative planning. AB - OBJECTIVES/HYPOTHESIS: To develop a tool for the calculation of surgical skull base defects and endonasal flap dimensions on preoperative computed tomography (CT) to aid surgical planning. STUDY DESIGN: Case series. METHODS: A literature search was conducted to identify all endonasal flaps. There were five basic models identified. These are the nasoseptal flap, anterior lateral nasal wall flap, bipedicled anterior septal flap, posterior pedicled inferior turbinate flap, and middle turbinate flap. Publications on the radioanatomy of endonasal flaps and surgical skull base defects were also identified. Using these descriptions as a reference, 38 radioanatomic variables were measured on CT scans obtained from 60 preoperative endonasal skull base surgery patients. These were then used to model endonasal flap coverage of six defects: transfrontal, transcribriform, transplanar, transsellar, transsphenoidal, and transclival. RESULTS: The nasoseptal provides adequate coverage for most defects. The posteriorly pedicled inferior turbinate flap is a good alternative, and provides better coverage of posterior skull base defects. The anterior lateral nasal wall flap is the best choice for transfrontal defects. The middle turbinate flap and bipedicled anterior septal flaps provide secondary options when larger flaps are not available. CONCLUSIONS: We have developed a simple tool for the calculation of endonasal flap coverage of surgical skull base defects on preoperative CT scans. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:1287-1293, 2018. PMID- 28990663 TI - Adaptation and validation of the Spanish version of the Tonsil and Adenoid Health Status Instrument. AB - OBJECTIVES/HYPOTHESIS: The Tonsil and Adenoid Health Status Instrument (TAHSI) is a disease-specific questionnaire, intended for completion by parents, for assessing quality of life related to tonsil and adenoid disease or its treatment in children with throat disorders. The aim of this study was to validate the Spanish adaptation of the TAHSI, thus allowing comparison across studies and international multicenter projects. STUDY DESIGN: Multicenter prospective instrument validation study. METHODS: Guidelines for the cross-cultural adaptation process from the original English-language scale into a Spanish language version were followed. The psychometric properties (reproducibility, reliability, validity, responsiveness) of the Spanish version of the TAHSI (s TAHSI) were assessed in 51 consecutive children undergoing adeno/tonsillectomy (both before and 6 months after surgery) and a separate cohort of 50 unaffected children of comparable age range. RESULTS: Test-retest reliability (gamma = 0.8) and internal consistency reliability (alpha = 0.95) were adequate. The s-TAHSI demonstrated satisfactory content validity (r > 0.40). The instrument showed excellent between-groups discrimination (P < .0001) and high responsiveness to change (effect size = 2.09). CONCLUSIONS: Psychometric testing of the s-TAHSI yielded satisfactory results, thus allowing assessment of the subjective severity of throat disorders in children. LEVEL OF EVIDENCE: 2c. Laryngoscope, 128:1469 1475, 2018. PMID- 28990664 TI - Hormone receptors analysis in idiopathic progressive subglottic stenosis. AB - OBJECTIVE: Idiopathic subglottic stenosis predominantly affects fertile and perimenopausal women. Estrogens and/or progesterone have been proposed as mediators of its pathogenesis by stimulating collagen deposition within the upper airway. We evaluated the presence and expression of estrogen-alpha (ER-alpha), estrogen-beta (ER-beta), and progesterone receptors (PR) in idiopathic stenotic patients. STUDY DESIGN: A retrospective analysis on 42 surgical specimens from idiopathic stenosis female patients (mean age, 52.4; age range, 31-79) and 28 gender- and age-matched controls. METHODS: Immunoreactivity of ER-alpha, ER-beta, and PR was calculated as the product of intensity (1 = weak, 2 = moderate, 3 = strong) and positive cell percentage (1-4, for < 10/10-50/50-80/ > 80%). This score was calculated on the stenotic and peristenotic tissues. Influence of menopausal status on hormonal expression and stenotic grade was tested. RESULTS: Stenosis showed ER-alpha overexpression versus peristenotic tissue and controls (score 6.6 +/- 4.4, 0.3 +/- 0.5, and 2.2 +/- 1.5, respectively; P < 0.001). Overexpression was even more marked for progesterone receptors (score 8.3 +/- 3.6, 0.8 +/- 0.6, and 1.0 +/- 0.7, respectively; P < 0.001). There was no expression of ER-beta in stenosis (score 0), whereas it was normally expressed in peristenotic tissue and controls (score 0.7 +/- 0.5 and 0.5 +/- 0.5; P < 0.001 vs. stenosis). Expression of ER-alpha was higher in postmenopausal stenotic patients (P < 0.01). This subgroup included a higher proportion of Cotton-Myer grade III stenosis than in premenopausal subjects (P < 0.001). CONCLUSION: An imbalance between ER-alpha, ER-beta, and PR is present in idiopathic stenosis patients. The hormonal background may be involved in inappropriate inflammation and increased stenosis susceptibility. Menopausal changes seem to play a role in both stenosis grade and receptor patterns. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:E72-E77, 2018. PMID- 28990665 TI - Transcutaneous electrical nerve stimulation (TENS) for fibromyalgia in adults. AB - BACKGROUND: Fibromyalgia is characterised by persistent, widespread pain; sleep problems; and fatigue. Transcutaneous electrical nerve stimulation (TENS) is the delivery of pulsed electrical currents across the intact surface of the skin to stimulate peripheral nerves and is used extensively to manage painful conditions. TENS is inexpensive, safe, and can be self-administered. TENS reduces pain during movement in some people so it may be a useful adjunct to assist participation in exercise and activities of daily living. To date, there has been only one systematic review in 2012 which included TENS, amongst other treatments, for fibromyalgia, and the authors concluded that TENS was not effective. OBJECTIVES: To assess the analgesic efficacy and adverse events of TENS alone or added to usual care (including exercise) compared with placebo (sham) TENS; no treatment; exercise alone; or other treatment including medication, electroacupuncture, warmth therapy, or hydrotherapy for fibromyalgia in adults. SEARCH METHODS: We searched the following electronic databases up to 18 January 2017: CENTRAL (CRSO); MEDLINE (Ovid); Embase (Ovid); CINAHL (EBSCO); PsycINFO (Ovid); LILACS; PEDRO; Web of Science (ISI); AMED (Ovid); and SPORTDiscus (EBSCO). We also searched three trial registries. There were no language restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs) or quasi-randomised trials of TENS treatment for pain associated with fibromyalgia in adults. We included cross-over and parallel-group trial designs. We included studies that evaluated TENS administered using non-invasive techniques at intensities that produced perceptible TENS sensations during stimulation at either the site of pain or over nerve bundles proximal (or near) to the site of pain. We included TENS administered as a sole treatment or TENS in combination with other treatments, and TENS given as a single treatment or as a course of treatments. DATA COLLECTION AND ANALYSIS: Two review authors independently determined study eligibility by assessing each record and reaching agreement by discussion. A third review author acted as arbiter. We did not anonymise the records of studies before assessment. Two review authors independently extracted data and assessed risk of bias of included studies before entering information into a 'Characteristics of included studies' table. Primary outcomes were participant reported pain relief from baseline of 30% or greater or 50% or greater, and Patient Global Impression of Change (PGIC). We assessed the evidence using GRADE and added 'Summary of findings' tables. MAIN RESULTS: We included eight studies (seven RCTs, one quasi-RCT, 315 adults (299 women), aged 18 to 75 years): six used a parallel-group design and two used a cross-over design. Sample sizes of intervention arms were five to 43 participants.Two studies, one of which was a cross-over design, compared TENS with placebo TENS (82 participants), one study compared TENS with no treatment (43 participants), and four studies compared TENS with other treatments (medication (two studies, 74 participants), electroacupuncture (one study, 44 participants), superficial warmth (one cross over study, 32 participants), and hydrotherapy (one study, 10 participants)). Two studies compared TENS plus exercise with exercise alone (98 participants, 49 per treatment arm). None of the studies measured participant-reported pain relief of 50% or greater or PGIC. Overall, the studies were at unclear or high risk of bias, and in particular all were at high risk of bias for sample size.Only one study (14 participants) measured the primary outcome participant-reported pain relief of 30% or greater. Thirty percent achieved 30% or greater reduction in pain with TENS and exercise compared with 13% with exercise alone. One study found 10/28 participants reported pain relief of 25% or greater with TENS compared with 10/24 participants using superficial warmth (42 degrees C). We judged that statistical pooling was not possible because there were insufficient data and outcomes were not homogeneous.There were no data for the primary outcomes participant-reported pain relief from baseline of 50% or greater and PGIC.There was a paucity of data for secondary outcomes. One pilot cross-over study of 43 participants found that the mean (95% confidence intervals (CI)) decrease in pain intensity on movement (100-mm visual analogue scale (VAS)) during one 30-minute treatment was 11.1 mm (95% CI 5.9 to 16.3) for TENS and 2.3 mm (95% CI 2.4 to 7.7) for placebo TENS. There were no significant differences between TENS and placebo for pain at rest. One parallel group study of 39 participants found that mean +/- standard deviation (SD) pain intensity (100-mm VAS) decreased from 85 +/- 20 mm at baseline to 43 +/- 20 mm after one week of dual-site TENS; decreased from 85 +/- 10 mm at baseline to 60 +/- 10 mm after single-site TENS; and decreased from 82 +/- 20 mm at baseline to 80 +/- 20 mm after one week of placebo TENS. The authors of seven studies concluded that TENS relieved pain but the findings of single small studies are unlikely to be correct.One study found clinically important improvements in Fibromyalgia Impact Questionnaire (FIQ) subscales for work performance, fatigue, stiffness, anxiety, and depression for TENS with exercise compared with exercise alone. One study found no additional improvements in FIQ scores when TENS was added to the first three weeks of a 12-week supervised exercise programme.No serious adverse events were reported in any of the studies although there were reports of TENS causing minor discomfort in a total of 3 participants.The quality of evidence was very low. We downgraded the GRADE rating mostly due to a lack of data; therefore, we have little confidence in the effect estimates where available. AUTHORS' CONCLUSIONS: There was insufficient high-quality evidence to support or refute the use of TENS for fibromyalgia. We found a small number of inadequately powered studies with incomplete reporting of methodologies and treatment interventions. PMID- 28990666 TI - Updating the research on the chemopreventive and therapeutic role of the peptide lunasin. AB - Chronic diseases have become the medical challenge of the 21st century because of their high incidence and mortality rates. Modulation of diet and lifestyle habits is considered as the best strategy for the prevention of these disorders. Health promoting benefits beyond their nutritional effects have been described for multiple dietary compounds. Among these compounds, the peptide lunasin is considered as one of the most promising. Naturally present in soybean, lunasin has been extensively studied in the last two decades because of its potential against chronic diseases such as cancer, cardiovascular and immunological disorders. The purpose of this article is to summarise the evidence on the presence of lunasin in soybean and derived foods, and its bioavailability once it is orally ingested. The protective and therapeutic effects of this peptide against cancer, oxidative stress, inflammation, and high cholesterol levels as well as the molecular mechanisms of action involved in these effects are also described in this review. (c) 2017 Society of Chemical Industry. PMID- 28990667 TI - The Indice Flesch-Szigriszt and Spanish Lexile Analyzer to evaluate Spanish patient education materials in otolaryngology. AB - OBJECTIVES/HYPOTHESIS: Evaluate the reading difficulty of Spanish patient education materials using the validated Indice Flesch-Szigriszt (INFLESZ) and Spanish Lexile Analyzer, and to identify relationships between English and Spanish readability formulas. STUDY DESIGN: Cross-sectional analysis. METHODS: All otolaryngology-related patient education articles written in Spanish from the health libraries of the top 10 US News & World Report-ranked hospitals, top 10 Doximity-ranked otolaryngology residencies, the American Academy of Otolaryngology-Head and Neck Surgery website, and the US National Library of Medicine online section on ears, nose and throat were collected. Reading difficulty was assessed using the INFLESZ and Spanish Lexile Analyzer. Additional readability assessments included the traditional English tools: Flesch-Kincaid Grade Level, Flesch Reading Ease Score, and the Simple Measure of Gobbledygook score. RESULTS: A total of 497 articles were reviewed. The average INFLESZ score for all articles was 57.75, which is considered normal and requires the reading ability of a student who finished Escuela Secundaria Obligatoria or 10th grade equivalent in the United States. The average Spanish Lexile measure for all articles was 1062L, equivalent to a reading level between the 6th and 12th grade. English readability tools calculated a more difficult reading level compared to Spanish tools when performed on the same text. CONCLUSIONS: Current Spanish patient education materials in otolaryngology may be too difficult for the average Spanish-speaking reader to understand. Future improvements may be warranted to improve the readability of educational materials and increase health literacy. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:E21-E26, 2018. PMID- 28990668 TI - Population panmixia and demographic expansion of a highly piscivorous marine fish Scomberomorus niphonius. AB - Population structure and demographic history of the Japanese Spanish mackerel Scomberomorus niphonius a highly piscivorous and migratory marine fish, were assessed using mitochondrial DNA control region sequences (n = 720) and microsatellite genotypes at five loci (n = 1331) for samples collected on Japanese coasts from 2001 to 2010. The population structure was panmictic and the haplotype and allele frequencies were temporally stable even during the recent recovery process. Demographic expansion was strongly supported throughout the Pleistocene, suggesting that the oscillating glacial and interglacial climate conditions in the Pleistocene had no substantial impact on the demographic history of S. niphonius. PMID- 28990669 TI - Effect of thyme oil-alginate-based coating on quality and microbial safety of fresh-cut apples. AB - BACKGROUND: Food preservation is critical for keeping fresh-cut products fresh, nutritious, safe, attractive and available for consumers. To improve the safety and quality of fresh-cut fruits, 15 essential oils (EOs) were screened to test the antimicrobial activity against Listeria monocytogenes (LM), Salmonella typhimurium (ST), Staphylococcus aureus (SA) and Escherichia coli O157:H7 (EC O157:H7). The effect of alginate-based edible coating (EC) incorporating different concentrations thyme oil on fresh-cut 'Red Fuji' apples was investigated. RESULTS: Results showed that thyme oil, cinnamon oil and oregano oil were more effective in inhibiting the microbes than other EOs. The result showed that the combined usage of 0.5 uL mL-1 thyme oil incorporated with alginate-based EC could significantly inhibit the microbial growth, respiration, weight loss, firmness and browning of fresh-cut 'Red Fuji' apples. CONCLUSION: The edible coating and natural additives like thyme oil could be used to preserve the quality of fresh-cut fruits. It revealed that EC incorporated with 0.5 uL mL 1 thyme oil can be a safe preservative for fresh-cut apples. (c) 2017 Society of Chemical Industry. PMID- 28990670 TI - Measuring consumers' interest in instant fortified pearl millet products: a field experiment in Touba, Senegal. AB - BACKGROUND: In Africa, food-processing industries are emerging fast, especially for cereals. New low-cost extrusion cookers give small enterprises an opportunity to enter the market for processed cereal products, in particular instant, fortified and flavoured mixes. Before engaging in the marketing of these products, consumers' interest needs to be assessed. This study used a combination of affective tests and experimental auctions with 200 consumers in Touba, Senegal, to evaluate four new products with conventional pearl millet flour as the control: instant pearl millet flour, instant pearl millet flour with added dry mango and carrot powder (naturally fortified), and the previous products with added conventional chemical micronutrient fortificants. RESULTS: During affective tests, consumers made little distinction between the five products in appearance, aroma, taste and overall appreciation. The experimental auctions showed that, without providing additional information on the products, there was no difference in 'willingness to pay' (WTP) between them. However, after that information is provided, consumers were willing to pay a modest premium for instant flour, and a large premium for added mango and carrot extract and for added micronutrients, but were not willing to pay a premium if those micronutrients came from natural sources. Income increased overall WTP, while education increased WTP for instant flour. CONCLUSION: There is a potential market in low-income African countries for instant and fortified cereal food products, but likely in the higher income and education groups. The increased cost needs to be compared to the premiums consumers are willing to pay. In the next step, the new and promising products could be tested in pilot markets, with target consumers. (c) 2017 Society of Chemical Industry. PMID- 28990671 TI - Reproductive isolation between sympatric Anguilla japonica and Anguilla marmorata. AB - Species-specific restriction fragment length polymorphism in the intron of the androgen receptor gene (ar5) was found in glass to silver-stage individuals of Anguilla japonica (n = 51) and A. marmorata (n = 21). The sequence analysis of 16S rDNA from 328 anguillid leptocephali collected in the North Equatorial Current of the western North Pacific Ocean revealed the specimens to be A. japonica (n = 194), A. marmorata (n = 128), A. bicolor pacifica (n = 5) and A. luzonensis (n = 1). All leptocephali of A. japonica and A. marmorata were monomorphic and did not share an allele at the ar5 locus, indicating that the two species are reproductively isolated. PMID- 28990673 TI - Clinical characteristics and outcomes of major salivary gland malignancies in children. AB - OBJECTIVES/HYPOTHESIS: Determine demographics, clinical characteristics, and survival rates for children with primary salivary gland malignancies. STUDY DESIGN: Retrospective, population-based cohort study. METHODS: All cases of primary salivary gland malignancies diagnosed between the years of 2002 and 2013 in patients ages 0 to 19 years were extracted from the National Cancer Institute's Surveillance, Epidemiology, and End Results database. Additional variables collected included age, gender, ethnicity, tumor histological subtype, tumor size, treatment modality, vitality status, and follow-up time. Kaplan-Meier survival curves were generated. RESULTS: Two hundred forty-five primary salivary gland malignancies were identified (220 parotid, 25 submandibular). Median age at diagnosis was 15 years. Most patients were female (59%), white (74%), and non Spanish/Hispanic/Latino (81%). Among parotid tumors, mean tumor size was 2.3 cm, and there were 109 (50%) mucoepidermoid carcinomas and 86 (39%) acinic cell carcinomas. Most patients underwent surgery (n = 212, 96%) and 64 (29%) received adjuvant radiation. At a mean follow-up of 62.4 months, 10 patients (5%) were deceased. Kaplan-Meier survival curves illustrated that black children exhibited higher mortality rates than white children (15.8% vs. 4.6%, log-rank = 0.0260) as did those who underwent adjuvant radiation (15.73% vs. 3.2%, log-rank = 0.0209). Among submandibular tumors, mean tumor size was 3.1 cm, and there were 11 (44%) mucoepidermoid carcinomas. All patients underwent surgery and most received adjuvant radiation (n = 15, 60%). At a mean follow-up of 51.25 months, one patient was deceased. CONCLUSIONS: Salivary gland malignancies in children and adolescents are rare. Overall survival for both parotid and submandibular tumors in children is good. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:1126-1132, 2018. PMID- 28990672 TI - Microdissection testicular sperm extraction in Finland - results of the first 100 patients. AB - INTRODUCTION: Testicular microdissection sperm extraction (MD-TESE) combined with intracytoplasmic sperm injection (ICSI) has made biological fatherhood possible for many men with the most severe form of male infertility, non-obstructive azoospermia. MD-TESE was introduced in Turku in 2008, and by 2015, 100 Finnish men with non-obstructive azoospermia have been operated on. MATERIAL AND METHODS: The average age of the men was 33 years at the time of surgery. Forty-eight had a needle biopsy previously and 56% had a testicular size <15 mL. The most common diagnoses were idiopathic (n = 65), Klinefelter syndrome (n = 15), operated cryptorchidism or torsion (n = 10), and Y chromosome microdeletion (n = 7). The pregnancy outcomes were followed. RESULTS: The sperm recovery rate (SRR) overall was 42%: 31% for idiopathic non-obstructive azoospermia, 40% for Klinefelter syndrome, 57% for Y chromosome microdeletion AZFc, 90% for previous testicular surgery (mostly for cryptorchidism; n = 10) and 67% for previous cytotoxic treatment (n = 3). SRR with histopathologic diagnosis Sertoli-cell-only was 29%, and 44% for spermatogenic arrest. Age did not affect the outcome of the surgery. Small testicular size seemed to predict a higher SRR. A previous needle biopsy did not predict a lower SRR. Surgical complications were rare. Of couples, 32 had at least one ICSI attempt, and 22 at least one live birth, giving a cumulative live birth rate of 69%. No major pregnancy complications occurred. CONCLUSIONS: Our SRR is comparable with international results, and the cumulative live birth rate similar to other ICSI indications in Finland. Physicians and specialists need to be made aware of new treatment options to enable biological fatherhood for men with non-obstructive azoospermia. PMID- 28990674 TI - The futility of intraoperative frozen section in the evaluation of follicular thyroid lesions. AB - OBJECTIVE: Investigate the utility of intraoperative frozen section (iFS) in patients with follicular thyroid lesions following publication of the 2015 American Thyroid Association (ATA) guidelines. STUDY DESIGN: Retrospective chart review. METHODS: Patient demographics, preoperative cytology, frozen pathology, and final pathology were reviewed on patients undergoing thyroid surgery at a tertiary care hospital in which iFS was utilized over a 5-year period. The test performance of iFS and the frequency of indicated completion/total thyroidectomies pre- and postpublication of the 2015 ATA guidelines were calculated. RESULTS: One hundred and one patients met inclusion criteria: 54 patients with follicular lesions of undetermined significance (FLUS) and 47 patients with a cytologic diagnosis of suspicious for follicular neoplasm/follicular neoplasm. The malignancy rate was 36%, but only 14% of malignancies were identified on iFS. A definitive benign or malignant diagnosis was given on iFS in only 21% of cases, and operative management was altered in two cases as a result of iFS. There was a statistically significant reduction in the frequency of indicated total/completion thyroidectomies based on high-risk features as a result of the 2015 ATA guidelines compared to prior recommendations (20.8% vs. 5.0%, P = < 0.001). None of these patients had findings on iFS that would have altered management intraoperatively. CONCLUSION: Intraoperative frozen section offers minimal diagnostic utility in the evaluation of follicular thyroid lesions. Updates in the 2015 ATA guidelines further diminish its potential to impact management intraoperatively. Significant improvements in its ability to identify malignancies would be needed to justify its use. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:1501-1505, 2018. PMID- 28990675 TI - The saline challenge-A test of injection laryngoplasty outcome. PMID- 28990676 TI - Arthroscopic approach and anatomy of the stifle joint in the rabbit. AB - OBJECTIVE: To describe a technique and normal findings for arthroscopy of the stifle in rabbits. STUDY DESIGN: Cadaver study. ANIMALS: Twenty cadaveric stifles from New Zealand White rabbits were examined. METHODS: The arthroscope was placed through a medial portal, and instrument portals were created on the lateral aspect of the joint. The same portals were used for examination of the entire joint and palpation of structures with a probe. RESULTS: Structures identified in the proximal aspect of the stifle included the suprapatellar pouch, suprapatella, patella, medial and lateral proximal recesses, medial and lateral trochlear ridges, trochlear groove. Structures identified in the distal aspect of the joint included the cranial and caudal cruciate ligaments, medial and lateral menisci, medial and lateral femoral condyles, the long digital extensor tendon, and the cranial meniscal ligaments were identified. All of the proximal structures could be seen in 16/20 limbs. Distally, the cranial cruciate ligament could be identified and manipulated most often (17/20 limbs), followed by the caudal cruciate ligament (11/20), the menisci (9/20), and condyles (9/20). The average examination time was 27 minutes. There was a variably present femorotibial membrane. CONCLUSION: We conclude that the arthoscopic evaluation of the stifle in rabbits is a viable surgical approach and could be used for rabbit models or to examine clinical cases with stifle pathology. Precise portal placement and adequate infrapatellar fat pad debridement were critical for success. PMID- 28990677 TI - Left ventricular twist is impaired in acromegaly: Insights from the three dimensional speckle tracking echocardiographic MAGYAR-Path Study. AB - INTRODUCTION: Acromegaly is a rare, chronic, disfiguring, and debilitating disease caused, in 90% of cases, by a benign monoclonal growth hormone-secreting pituitary adenoma. The present study aimed to assess left ventricular (LV) rotational and twist mechanics in acromegalic patients and to compare their results to age- and gender-matched healthy controls. METHODS: The present study comprised 24 acromegalic patients, from which 4 were excluded due to insufficient image quality (mean age: 57.8 +/- 13.7 years, 7 men). The control group consisted of 18 age- and gender-matched healthy individuals (mean age: 54.8 +/- 6.9 years, 8 men). RESULTS: In 4 out of 20 acromegalic patients, LV showed near absence of twist, as the so-called LV "rigid body rotation" (RBR). Between all acromegalic patients without LV-RBR and controls, both LV basal (-3.76 +/- 1.73 vs. -6.17 +/- 2.66 degrees , P = .004) and apical rotation (6.12 +/- 4.03 vs. 10.81 +/- 3.65 degrees , P = .001) and LV twist (9.88 +/- 4.74 vs. 16.98 +/- 3.88 degrees , P < .001) differed significantly. Between active and nonactive acromegaly subgroups, only the time-to-peak LV twist (377 +/- 78 vs. 229 +/- 97 ms, P = .005) showed significant difference. CONCLUSIONS: Acromegaly is associated with impaired LV rotation and twist as assessed by 3-dimensional speckle tracking echocardiography. LV-RBR is a frequent phenomenon in acromegaly. PMID- 28990679 TI - Sonographic evaluation of the endochondral ossification process of the thyroid cartilage in children. AB - PURPOSE: To determine the sonographic appearances of the endochondral ossification process of the thyroid cartilage in children. METHODS: Thyroid cartilage sonography (US) of 420 children was performed with a high-resolution linear-array transducer. Right and left laminae of the thyroid cartilage, including the inferior horns, were examined. Ossification foci were evaluated for their presence, location, shape, size, echo pattern, and number. RESULTS: Four hundred nineteen children, 239 girls and 180 boys, were enrolled in the study with a mean age of 109.8 +/- 60.7 months. Ossification foci were found in 167 children (39.9%). First ossification focus detection age was 72 months in girls and 79 months in boys. On both laminae, the most frequent appearance of the ossification focus was hypoechoic (right: 94.8%, left: 93.5%). Prevalence and number of ossification foci increased with age in each sex. The shape of the ossification foci in both laminae was generally nonexpansile (right: 92.9%, left: 93.5%). CONCLUSION: Endochondral ossification process of the thyroid cartilage begins in the first decade with extracellular matrix changes, which can be detected as hypoechoic foci by US. These foci can be expansile, and radiologists should be aware of this entity to avoid misdiagnosing them as abnormal masses. PMID- 28990680 TI - Baseline NS5A resistance associated substitutions may impair DAA response in real world hepatitis C patients. AB - Oral DAA have demonstrated high efficacy as treatment of hepatitis C. However, the presence of resistance-associated substitutions (RAS) at baseline has occasionally been associated with impaired treatment response. Herein, we examined the impact of baseline RAS at the HCV NS5A gene region on treatment response in a real-life setting. All hepatitis C patients treated with DAA including NS5A inhibitors at our institution were retrospectively examined. The virus NS5A gene was analyzed using population sequencing at baseline and after 24 weeks of completing therapy in all patients that failed. All changes recorded at positions 28, 29, 30, 31, 32, 58, 62, 92, and 93 were considered. A total of 166 patients were analyzed. HCV genotypes were as follows: G1a (31.9%), G1b (48.2%), G3 (10.2%), and G4 (9.6%). Overall, 69 (41.6%) patients were coinfected with HIV and 46.7% had advanced liver fibrosis (Metavir F3-F4). Sixty (36.1%) patients had at least one RAS at baseline, including M28A/G/T (5), Q30X (12), L31I/F/M/V (6), T58P/S (25), Q/E62D (1), A92 K (7), and Y93C/H (15). Overall, 4.8% had two or more RAS, being more frequent in G4 (12.5%) followed by G1b (6.3%) and G1a (1.9%). Of 10 (6%) patients that failed DAA therapy, five had baseline NS5A RAS. No association was found for specific baseline RAS, although changes at position 30 were more frequent in failures than cures (22.2% vs 6.4%, P = 0.074). Moreover, the presence of two or more RAS at baseline was more frequent in failures (HR: 7.2; P = 0.029). Upon failure, six patients showed emerging RAS, including Q30C/H/R (3), L31M (1), and Y93C/H (2). Baseline NS5A RAS are frequently seen in DAA-naive HCV patients. Two or more baseline NS5A RAS were found in nearly 5% and were significantly associated to DAA failure. Therefore, baseline NS5A testing should be considered when HCV treatment is planned with NS5A inhibitors. PMID- 28990678 TI - Spatiotemporal modeling of laser tissue soldering using photothermal nanocomposites. AB - OBJECTIVE: Laser tissue soldering using photothermal solders is a technology that facilitates rapid sealing using heat-induced changes in the tissue and the solder material. The solder material is made of gold nanorods embedded in a protein matrix patch that can be placed over the tissue rupture site and heated with a laser. Although laser tissue soldering is an attractive approach for surgical repair, potential photothermal damage can limit the success of this approach. Development of predictive mathematical models of photothermal effects including cell death, can lead to more efficient approaches in laser-based tissue repair. METHODS: We describe an experimental and modeling investigation into photothermal solder patches for sealing porcine and mouse cadaver intestine sections using near-infrared laser irradiation. Spatiotemporal changes in temperature were determined at the surface as well as various depths below the patch. A mathematical model, based on the finite element method, predicts the spatiotemporal temperature distribution in the patch and surrounding tissue, as well as concomitant cell death in the tissue is described. RESULTS: For both the porcine and mouse intestine systems, the model predicts temperatures that are quantitatively similar to the experimental measurements with the model predictions of temperature increase often being within a just a few degrees of experimental measurements. CONCLUSION: This mathematical model can be employed to identify optimal conditions for minimizing healthy cell death while still achieving a strong seal of the ruptured tissue using laser soldering. Lasers Surg. Med. 50:143-152, 2018. (c) 2017 Wiley Periodicals, Inc. PMID- 28990681 TI - Limb shortening as a strategy for limb sparing treatment of appendicular osteosarcoma of the distal radius in a dog. AB - OBJECTIVE: To develop and report a novel limb sparing technique for the distal radius in a dog. STUDY DESIGN: Case report. ANIMAL: A 14-year-old, female spayed Labrador Retriever with an osteosarcoma of the right distal radius and a pathological fracture. A previous mast cell tumor had been treated 5 years prior to presentation with marginal excision and a full-course radiation over the right metacarpal bones. The dog had received 2 doses of palliative radiation just prior to presentation. METHODS: A standard resection of the distal radius was used as a strategy to salvage the limb. Instead of replacing the 6-cm bone defect with an endoprosthesis, the limb was acutely shortened and a carpal arthrodesis plate was applied. RESULTS: Postoperative function was good and limb shortening was well tolerated. Radiographic evidence of early bone healing was noted at the osteotomy site. The dog experienced 3 postoperative complications: a focal area of skin necrosis managed successfully via surgical revision; infection resolving after long-term antibiotherapy; and a fracture of the third metacarpal bone through a screw hole, managed via screw removal and a custom external prosthesis. The patient was euthanatized due to presumptive chemotherapy complications 127 days after the procedure. CONCLUSION: Limb shortening limb salvage is technically feasible and can result in excellent limb use postoperatively, in spite of a significant loss in limb length. PMID- 28990682 TI - Ex vivo feasibility study of endoscopic intraductal laser ablation of the breast. AB - OBJECTIVE: To determine the feasibility and safety of breast endoscopic thulium laser ablation for treatment of intraductal neoplasia. STUDY DESIGN: Ductoscopy is a minimally invasive endoscopic approach of the milk ducts of the breast via the nipple. Besides diagnosis in women with pathologic nipple discharge (PND), it allows non-invasive removal of intraductal lesions with a stalk like papillomas. Removal, however, is often incomplete and flat lesions cannot be targeted. We therefore developed laser ductoscopy. METHODS: Dosimetry of laser ductoscopy was assessed in thirteen mastectomy specimens, applying power settings of 1-5 W with 100-1000 ms pulsed exposure to a 375-MUm outer diameter thulium fiber laser. Subsequently histology was obtained from the breast tissue that was treated with the Thulium laser. RESULTS: Endoscopic view was maintained during ductoscopic laser ablation at 1-3 W. Increasing power to 4-5 W caused impaired vision due to shrinkage of the main duct around the ductoscope tip. Histology revealed localized ablation of the duct wall. CONCLUSION: We show for the first time that laser ductoscopy is technically feasible. The Thulium laser enables a superficial intraductal ablation and is a useful tool for intraductal interventions. An in vivo prospective study is needed to further demonstrate its potential. Lasers Surg. Med. 50:137-142, 2018. (c) 2017 Wiley Periodicals, Inc. PMID- 28990683 TI - The effect of unit, depth, and probe load on the reliability of muscle shear wave elastography: Variables affecting reliability of SWE. AB - PURPOSE: There is currently no standardized method for muscle shear wave elastography (SWE). The objective of this study was to investigate the effect of unit of measurement, depth, and probe load on the reliability of muscle SWE. METHODS: The vastus lateralis, biceps femoris, biceps brachii, and abductor digiti minimi muscles were scanned on 20 healthy participants. The SWE readings were measured in shear wave velocity (m/s) and Young's modulus (kPa). Three acquisitions of varying depths were acquired from vastus lateralis. Minimal probe load was compared with the use of a standoff gel layer. Three repeated measurements were acquired to assess reliability using intraclass correlations (ICC). RESULTS: The mean elasticity varied across muscle groups and ranged from 1.54 m/s for biceps femoris to 2.55 m/s for abductor digiti minimi (difference = 1.01 m/s [95% confidence interval, CI = 0.92, 1.10]). Reporting readings in meters per second resulted in higher ICC of 0.83 (0.65, 0.93) in comparison to 0.77 (0.52, 0.90) for kilopascal for the vastus lateralis muscle only. Variance increased proportionally with depth reaching 0.17 (equivalent to +/-0.82 m/s) at 6 cm. Using a standoff gel decreased ICC to 0.63 (0.20, 0.84) despite similar mean elasticity readings to minimal probe load. CONCLUSIONS: Different acquisition and technical factors may significantly affect the reliability of SWE in skeletal muscles. Readings acquired in the unit of shear wave velocity (m/s) from depths less than 4 cm using a minimal probe load without a standoff gel yielded the best reliability. PMID- 28990684 TI - A new scenario in the immunohistochemical diagnosis of cutaneous leishmaniasis. AB - Cutaneous lesions of leishmaniasis are easy to diagnose when clinically obvious or when amastigotes are numerous in the biopsy. However, this is not always the case. In difficult cases, the diagnosis of leishmaniasis requires a reliable tool to identify the microorganisms. The identification of the parasite via microscope has a superior sensitivity to that of culture, and molecular techniques, such as polymerase chain reaction (PCR), highly improve the sensitivity of the diagnosis. Alternatively, immunohistochemistry has emerged as an affordable alternative to PCR. Several laboratories have produced their own antibodies against Leishmania and seem satisfied with the results. Nevertheless, most of these antibodies are not commercialized or standardized. Pathology also welcomed the unexpected positivity of amastigotes with certain clones of anti-CD1a. The latter does not universally stain all species of Leishmania, with a low sensitivity for New World species. In conclusion, although anti-CD1a is a reliable complementary tool in the diagnosis of leishmaniasis, pathologists should familiarize themselves with one of the specific antibodies against Leishmania and globalize its use, standardizing and adapting the technique. PMID- 28990685 TI - National trends in otolaryngology intern curricula following Accreditation Council for Graduate Medical Education changes. AB - OBJECTIVES/HYPOTHESIS: In 2016, Accreditation Council for Graduate Medical Education (ACGME) requirements for curriculum and resident experiences were modified to require entering postgraduate year (PGY)-1 residents to spend 6 months of structured education on otolaryngology-head and neck surgery (ORL-HNS) rotations. We aimed to determine how ORL-HNS training programs have adapted curricula in response to 2016 ACGME curriculum requirement changes. STUDY DESIGN: Survey study. METHODS: A national survey of ACGME-accredited ORL-HNS programs was distributed via the Otolaryngology Program Directors Organization. RESULTS: Thirty-seven program directors responded (34.9%). Most common ORL-HNS rotations included general otolaryngology (80.6% of programs, up to 6 months) and head and neck oncology (67.7%, up to 4 months), though more months are also spent on other subspecialty rotations (laryngology, otology, rhinology, and pediatrics) than previously. All programs continue at least 1 month of anesthesiology, intensive care unit, and general surgery. Programs have preferentially eliminated rotations in emergency medicine (77% decrease) and additional months on general surgery (48% decrease). Curricula have incorporated supplemental teaching modalities including didactic lectures (96.3% of programs), simulation (66.7%), dissection courses (63.0%), and observed patient encounters (55.5%), to a greater degree following ACGME changes. More interns are involved in shared call responsibilities than in previous years (70.4% vs. 51.8%). A stable minority of interns take the Otolaryngology Training Examination (approximately 20%). CONCLUSIONS: New ACGME requirements have challenged ORL-HNS training programs to develop effective 6-month rotation schedules for PGY-1 residents. Significant variation exists between programs, and evaluation of first-year curricula and readiness for PGY-2 year is warranted. LEVEL OF EVIDENCE: NA Laryngoscope, 1811 1816, 2018. PMID- 28990686 TI - Hierarchical imputation of systematically and sporadically missing data: An approximate Bayesian approach using chained equations. AB - In health and medical sciences, multiple imputation (MI) is now becoming popular to obtain valid inferences in the presence of missing data. However, MI of clustered data such as multicenter studies and individual participant data meta analysis requires advanced imputation routines that preserve the hierarchical structure of data. In clustered data, a specific challenge is the presence of systematically missing data, when a variable is completely missing in some clusters, and sporadically missing data, when it is partly missing in some clusters. Unfortunately, little is known about how to perform MI when both types of missing data occur simultaneously. We develop a new class of hierarchical imputation approach based on chained equations methodology that simultaneously imputes systematically and sporadically missing data while allowing for arbitrary patterns of missingness among them. Here, we use a random effect imputation model and adopt a simplification over fully Bayesian techniques such as Gibbs sampler to directly obtain draws of parameters within each step of the chained equations. We justify through theoretical arguments and extensive simulation studies that the proposed imputation methodology has good statistical properties in terms of bias and coverage rates of parameter estimates. An illustration is given in a case study with eight individual participant datasets. PMID- 28990687 TI - Phrenicoabdominal venotomy for tumor thrombectomy in dogs with adrenal neoplasia and suspected vena caval invasion. AB - OBJECTIVE: To describe a technique for tumor thrombectomy by phrenicoabdominal venotomy in dogs with adrenal neoplasia and suspected caval invasion and to report complications and outcomes associated with the procedure. STUDY DESIGN: Retrospective case series. ANIMALS: Eight client-owned dogs with invasive adrenal tumors. METHODS: Medical records of dogs diagnosed with adrenal tumors with extension of thrombus into the phrenicoabdominal vein (PAV) and vena cava were reviewed. Cases where phrenicoabdominal venotomy without cavotomy for thrombus resection was performed were included. Data collected from the medical records included signalment, clinical signs, physical examination findings, diagnostic imaging results, preoperative laboratory testing, surgical technique, surgical and postoperative complications and outcome. RESULTS: Phrenicoabdominal venotomy was successful in removal of vena caval thrombosis in 7 of 8 dogs. In one case, an attempt was made to remove a large vena caval thrombus through a distended PAV resulting in fragmentation of the thrombus and the need to extend the incision into the vena cava. In all dogs, complete removal of tumor thrombus was achieved. Two dogs died in the perioperative period, one from cardiopulmonary arrest and a second from bronchopneumonia and pancreatitis. The remaining 6 dogs were discharged from the hospital. CONCLUSION: Thrombectomy through a phrenicoabdominal venotomy may obviate the need for a cavotomy in a subset of dogs with invasive adrenal neoplasia. PMID- 28990688 TI - Well-differentiated papillary mesothelioma of tunica vaginalis testis of unknown malignant potential: Sonographic appearance. AB - Paratesticular mesothelioma is a rare differential diagnosis in the presence of scrotal hydrocele. A 17-year-old boy presented with a 3-year history of progressive hydrocele. Sonography revealed a large left paratesticular mass within the hydrocele. Serum tumor markers were negative. Left hydrocelectomy was performed and pathological analysis of the epididymal mass revealed a well differentiated papillary mesothelioma. We discuss the sonographic and pathological findings of this rare neoplasm. PMID- 28990689 TI - Control of GABARAP-mediated autophagy by the Golgi complex, centrosome and centriolar satellites. AB - Within minutes of induction of autophagy by amino-acid starvation in mammalian cells, multiple autophagosomes form throughout the cell cytoplasm. During their formation, the autophagosomes sequester cytoplasmic material and deliver it to lysosomes for degradation. How these organelles can be so rapidly formed and how their formation is acutely regulated are major questions in the autophagy field. Protein and lipid trafficking from diverse cell compartments contribute membrane to, or regulate the formation of the autophagosome. In addition, recruitment of Atg8 (in yeast), and the ATG8-family members (in mammalian cells) to autophagosomes is required for efficient autophagy. Recently, it was discovered that the centrosome and centriolar satellites regulate autophagosome formation by delivery of an ATG8-family member, GABARAP, to the forming autophagosome membrane, the phagophore. We propose that GABARAP regulates phagophore expansion by activating the ULK complex, the amino-acid controlled initiator complex. This finding reveals a previously unknown link between the centrosome, centriolar satellites and autophagy. PMID- 28990690 TI - Contrast-enhanced transoral carotid ultrasonography for the diagnosis and follow up of extracranial internal carotid artery dissection: A case report. AB - A 56-year-old woman was admitted to our hospital because of amaurosis fugax. The carotid angiogram showed irregularly stenotic lesions of the left and right internal carotid arteries (ICAs), suggestive of dissection. Follow-up evaluation was performed by transoral carotid ultrasonography (TOCU) with contrast enhancement (CE), which yielded better vessel lumen and intramural hematoma visualization than color Doppler imaging. CE-TOCU is useful for evaluating ICA dissections that extends to the high cervical portion. PMID- 28990691 TI - Comparison of 2 training programs for basic laparoscopic skills and simulated surgery performance in veterinary students. AB - OBJECTIVE: To compare the effects of 2 training curricula on laparoscopic skills and performance of simulated surgery in veterinary students. STUDY DESIGN: Prospective study. SAMPLE POPULATION: Veterinary students (n = 33) with no prior hands-on experience in minimally invasive surgery. METHODS: Basic laparoscopic skills (BLS) were assessed based on 5 modified McGill inanimate system for training and evaluation of laparoscopic skills. Motion metrics and an objective structured assessment of technical skills (OSATS) were used to evaluate surgical skills during a simulated laparoscopic cholecystectomy performed in an augmented reality simulator. Students were randomly assigned to either skill-based (group A) or procedural-based (group B) training curriculum. Both tests were performed prior to and after a 10-session training curriculum. RESULTS: Post-training BLS results were improved in both training groups (P < .001). Seven participants completed both presimulated and postsimulated laparoscopic cholecystectomy, preventing paired analysis. Based on motion metrics analysis, participants completed tasks in a shorter time (P = .0187), and with better economy of movement (P = .0457) after training. No difference was detected in OSATS before and after training. CONCLUSION: Both training curricula improved BLS, but significant differences were not detected between the procedural-based training program and basic skills training alone in veterinary students. Motion metrics such as time, economy of movement, and instrument path were superior to an OSATS, when assessing surgical performance. Further studies are needed to compare the effects of different simulators on the training of veterinarians with diverse laparoscopic surgical experience. PMID- 28990692 TI - Functional results of free tissue transfer for complex heel-calcaneal defects. AB - BACKGROUND: Loss of soft tissue in heel-calcaneal region is frequently caused by trauma, infection, or tumors. Limited availability of similar tissue becomes challenging, therefore, the use of free tissue transfer offers a solution. Our aim is to describe long term functional outcome of different free tissue transfers for these defects. PATIENTS AND METHODS: We retrospectively reviewed 24 consecutive cases of the heel-calcaneal defect between January 2009 and December 2014. The free fasciocutaneous perforator (FCP) flaps were performed in 14 cases and free muscle flaps with skin graft in 10 cases. The postoperative complications, range of motion and ability of ambulation or exercise were administered to evaluate functional results. RESULTS: The average follow-up period was 26.5 months. The survival of free flap was 100%. Early complication included venous thrombosis, infection and edge dehiscence was noted in 8 cases. Late complication with insensate ulcers developed in 3 cases (1 cases in FCP flap, 2 cases in muscle flap). All ulcers healed spontaneously without surgical intervention. The postoperative average range of motion of ankle regained 52.79 degree in FCP flap group and 56.4 degree in muscle flap group. The ability of ambulation or exercise returned in 13 cases in FCP group (13/14) and 9 cases in muscle flap group (9/10). No differences of complication rate (P = .403), ROM (P = .363) or functional evaluation (P = .803) could be found between these two groups. CONCLUSIONS: Both FCP flap and muscle flaps provided the similar and excellent functional results in resurfacing of heel-calcaneal defects after long term follow up. PMID- 28990693 TI - Impact of medialization laryngoplasty on dynamic nanomechanical vocal fold structure properties. AB - OBJECTIVES/HYPOTHESIS: Although the primary goal of medialization laryngoplasty is to improve glottic closure, implant placement is also likely to alter the biomechanical properties of the vocal fold (VF). We sought to employ novel, nanoscale technology to quantify these properties following medialization based on the hypothesis that different medialization materials will likely yield differential biomechanical effects. STUDY DESIGN: Ex vivo. METHODS: Nine pig larynges were divided into three groups: control, Silastic (Dow Corning, Midland, Michigan, U.S.A.) block medialization, or Gore-Tex (W.L. Gore & Associates, Newark, Delaware) medialization. Laryngoplasty was performed on excised, intact larynges. The larynges were then bisected in the sagittal plane and each subjected to dynamic nanomechanical analysis (nano-DMA) at nine locations using a 250-MUm flat-tip punch and frequency sweep-load profile across the free edge of the VF and inferiorly along the conus elasticus. RESULTS: Silastic block and Gore Tex implant introduced increased storage and loss moduli. Overall, storage moduli mean (maximum) increased from 38 kilopascals (kPa) (119) to 72 kPa (422) and 129 kPa (978) in control, Gore-Tex, and Silastic implants, respectively. Similarly, loss moduli increased from 13 kPa (43) to 22 kPa (201) and 31 kPa (165), respectively. Moduli values varied widely by location in the Silastic block and Gore-Tex groups. At the free VF edge, mean (maximum) storage moduli were lowest in the Gore-Tex group, 20 kPa (44); compared to control, 34.5 kPa (86); and Silastic, 157.9 kPa (978), with similar loss and complex moduli trends. CONCLUSION: Medialization laryngoplasty altered VF structure biomechanical properties; Silastic and Gore-Tex implants differentially impact these properties. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:1163-1169, 2018. PMID- 28990694 TI - Suprafascial versus traditional harvesting technique for free antero lateral thigh flap: A case-control study to assess the best functional and aesthetic result in extremity reconstruction. AB - Clinical applications of ALT flap have currently extended to extremity (hand and foot) as well as oral cavity reconstruction. In these anatomical areas, the traditional harvesting technique presents a few disadvantages such as bulkiness of the recipient site and potential donor site morbidity including damage to the deep fascia and skin graft adhesions. The purpose of the present study was to compare the functional and aesthetic outcomes of upper and lower extremity reconstruction with either suprafascial or subfascial harvested anterolateral (ALT) flaps. Sixty patients who underwent hand or foot reconstruction with an ALT flap between January 2013 and January 2015 were included in the study (34 flaps elevated on a subfascial plane and 26 on a suprafascial plane). Group 1 (subfascial harvested ALT flap) was composed of 23 male and 11 female patients with an average age of 53.4 years (range, 36-72 years). Group 2 (suprafascial harvested ALT flap) was composed of 18 male and 8 female patients with an average age of 48.7 years (range, 32-69 years). Surgical indication was tumor resection for 20 patients in group 1 and 16 patients in group 2, chronic ulcer for 8 patients in group 1 and 6 patients in group 2, and trauma for 6 patients in group 1 and 4 patients in group 2. Complications were documented. Aesthetic outcomes were considered in terms of bulkiness of the recipient site, subsequent request for a debulking procedure, and donor site morbidity. Donor site scars were evaluated for cosmesis using a modified Hollander Wound Evaluation Scale (HWES). Skin grafts outcomes were assessed according to the modified Vancouver Scar Scale (VSS). Functional outcome at the recipient site was measured using the Enneking functional outcome score (ESS). Total range of motion (ROM) was recorded. All flaps were successfully elevated with at least one viable perforator with both approaches. The survival rates of suprafascial and subfascial harvested ALT flaps were 96.2 and 97% respectively (P = .85). The mean flap size was 110.4 +/- 27.8 cm2 in group 1 and 159.7 +/- 44.4 cm2 in group 2. The average flap thickness was 26.2+/- 5.2 mm in group 1 and 13.9 mm +/- 4.1 in group 2. Complications included total flap loss (1 case in group 1 and 1 case in group 2), partial flap loss (2 cases in group 1 and 1 case in group 2), skin graft failure (3 cases in group 1), and muscle herniation at the donor site (1 case in group 1; P < .17). Secondary debulking procedures were needed for 20 flaps in the subfascial group and for one flap in the suprafascial group (P-value <.01). Donor site closure with skin grafts was necessary in 42 cases: 32 in group 1 and 10 in group 2. The suprafascial harvested ALT flap group reported a significant difference in terms of donor site morbidity. The HWES score of donor site scars was significantly lower in group 1 (mean 1.2 +/- 0.54) than in group 2 (mean 2.4 +/- 0.58), P < .01. Similarly, the VSS score for skin graft outcomes was lower in patients of group 1 (mean 4.5 +/- 0.93) than in patients of group 2 (mean 6.7 +/- 0.96), P < .01. There was also a significant lower score of postoperative ESS in patients of group 1 (mean 21.2 +/- 3.4) when compared with patients of group 2 (mean 23.6 +/- 2.7), P < .01. Total ROM improved on average 60 degrees after surgery (P-value <.01). The suprafascial plane for elevating ALT flaps presented several advantages over the traditional subfascial approach in terms of functional and aesthetic outcomes, providing a thin flap allowing increased versatility to achieve better contour of flap, and minimizing the need for secondary debulking. PMID- 28990695 TI - Synergistic Hydrogenation over Palladium through the Assembly of MIL-101(Fe) MOF over Palladium Nanocubes. AB - Enhancing catalytic performance of metal nanoparticles is highly sought for many industrial catalytic processes. In this regard, assembly of crystalline porous super-tunable metal-organic frameworks (MOFs) around preformed metal nanoparticles is an attractive prospect as this strongly influences the activity of the entire nanoparticle surface. Herein, we assembled a MlL-101(Fe) MOF onto the Pd nanocubes and evaluated the catalytic properties of the hybrid material for the hydrogenation of the alpha,beta-unsaturated carbonyl compounds cinnamaldehyde, crotonaldehyde, and beta-ionone. Owing to the synergestic effects originating from the Lewis acid sites present on MOF and Pd active sites, striking improvements in the activities and selectivities were observed for the Pd?MIL-101(Fe) hybrid material. The turnover frequency (TOF) values increased up to roughly 20 fold and in all three studied substrates, C=C was preferentially hydrogenated compared to C=O. Furthermore, the Pd?MIL-101(Fe) catalyst was readily reusable and highly stable. PMID- 28990696 TI - Modulation of Th17 and regulatory T-cell responses during murine pregnancy contributes to increased maternal susceptibility to Salmonella Typhimurium infection. AB - PROBLEM: Salmonella Typhimurium (S. Tm) infection in pregnant mice results in massive placental infection, fetal loss, and exacerbated systemic infection. The Th17 host response can aid control of S. Tm infection, whereas successful pregnancy correlates to a dampened inflammatory and enhanced regulatory T-cell (Treg) response. METHOD OF STUDY: Mice were infected systemically with S. Tm and tissue bacterial burden, splenic Th17 and Treg cell numbers, and serum cytokines were analyzed. Splenic and/or placental mRNA expression of IL-17A, RORgamma-t, IL 10, and TNF was determined. The effects of in vivo CD25+ cell depletion and TLR4 blockade on the course of S. Tm infection and Th17 response were determined. RESULTS: Enhanced S. Tm burden in pregnant mice was associated with time dependent increased serum inflammatory cytokines. In vivo, TLR4 blockade reduced splenic S. Tm burden, suggesting detrimental TLR4-mediated inflammation. However, the splenic and placental Th17 response was reduced in S. Tm-infected pregnant mice relative to non-pregnant controls. Alternatively, there was an increase in splenic Treg frequency in pregnant mice and depletion of this subset reduced bacterial burden and increased the Th17 response. CONCLUSION: Downregulation of Th17 cell responses by Tregs during pregnancy potentially contributes to exacerbation of S. Tm infection in pregnant mice. PMID- 28990697 TI - C9/12 Ribbon-Like Structures in Hybrid Peptides Alternating alpha- and Thiazole Based gamma-Amino Acids. AB - According to their restricted conformational freedom, heterocyclic gamma-amino acids are usually considered to be related to Z-vinylogous gamma-amino acids. In this context, oligomers alternating alpha-amino acids and thiazole-based gamma amino acids (ATCs) were expected to fold into a canonical 12-helical shape as described for alpha/gamma-hybrid peptides composed of cis-alpha/beta-unsaturated gamma-amino acids. However, through a combination of X-ray crystallography, NMR spectroscopy, FTIR experiments, and DFT calculations, it was determined that the folding behavior of ATC-containing hybrid peptides is much more complex. The homochiral alpha/(S)-ATC sequences were unable to adopt a stable conformation, whereas the heterochiral alpha/(R)-ATC peptides displayed novel ribbon structures stabilized by unusual C9/12 -bifurcated hydrogen bonds. These ribbon structures could be considered as a succession of pre-organized gamma/alpha dipeptides and may provide the basis for designing original alpha-helix mimics. PMID- 28990699 TI - Novel AMER1 frameshift mutation in a girl with osteopathia striata with cranial sclerosis. PMID- 28990698 TI - Psychosocial co-morbidities in Interstitial Cystitis/Bladder Pain syndrome (IC/BPS): A systematic review. AB - AIMS: Psychosocial factors amplify symptoms of Interstitial Cystitis (IC/BPS). While psychosocial self-management is efficacious in other pain conditions, its impact on an IC/BPS population has rarely been studied. The objective of this review is to learn the prevalence and impact of psychosocial factors on IC/BPS, assess baseline psychosocial characteristics, and offer recommendations for assessment and treatment. METHOD: Following PRISMA guidelines, primary information sources were PubMed including MEDLINE, Embase, CINAHL, and GoogleScholar. Inclusion criteria included: (i) a clearly defined cohort with IC/BPS or with Chronic Pelvic Pain Syndrome provided the IC/BPS cohort was delineated with quantitative results from the main cohort; (ii) all genders and regions; (iii) studies written in English from 1995 to April 14, 2017; (iv) quantitative report of psychosocial factors as outcome measures or at minimum as baseline characteristics. RESULTS: Thirty-four of an initial 642 articles were reviewed. Quantitative analyses demonstrate the magnitude of psychosocial difficulties in IC/BPS, which are worse than average on all measures, and fall into areas of clinical concern for 7 out of 10 measures. Meta-analyses shows mean Mental Component Score of the Short-Form 12 Health Survey (MCS) of 40.80 (SD 6.25, N = 2912), where <36 is consistent with severe psychological impairment. Averaged across studies, the population scored in the range seen in clinical depression (CES-D 19.89, SD 13.12, N = 564) and generalized anxiety disorder (HADS-A 8.15, SD 4.85, N = 465). CONCLUSION: The psychological impact of IC/BPS is pervasive and severe. Existing evidence of treatment is lacking and suggests self-management intervention may be helpful. PMID- 28990700 TI - Application of the Eighth Edition American Joint Committee on Cancer Staging System for HPV-Related Oropharyngeal Cancer Treated With Transoral Robotic Surgery. AB - OBJECTIVE: Analyze patients treated with transoral robotic surgery (TORS) in the context of the eighth edition of the American Joint Committee on Cancer (AJCC) staging system. METHODS: Retrospective cohort study including 110 human papillomavirus-related oropharyngeal cancer (HPV+OPC) patients with a minimum 1 year follow-up treated with TORS between 2007 to 2016. Kaplan-Meier methods were used to estimate 3-year disease-free survival and assess differences in recurrence. RESULTS: One hundred and ten patients with a median follow-up of 54 months were analyzed. Of those, 85% of patients were male, with a median age of 60. Twenty-two percent of patients received no adjuvant therapy; 43% received adjuvant radiation; and 35% underwent adjuvant chemoradiation. Extracapsular spread was identified in 24% of patients. Overall survival was 100%, with estimated 3-year disease-free survival (DFS) (95% confidence interval) of 87% (77, 93). Under the seventh edition of the AJCC, 5% of patients were stage I; 11% were stage II; 26% were stage III; and 57% were stage IVa. Twenty-seven patients (25%) were upstaged on final pathology, whereas 15 patients (14%) were downstaged. Under the eighth edition of the AJCC, 94% of patients were stage I for both clinical and pathologic staging systems. Six patients (6%) were upstaged on final pathology, whereas six patients (6%) were downstaged. No factors demonstrated statistical significance for DFS. Within pathologic stage I, Kaplan Meier estimates for DFS did not reach statistical significance. CONCLUSION: The majority of patients undergoing TORS for HPV + OPC are stage I under the eighth edition of the AJCC staging system, with limited pathologic re-staging compared with the prior system. Oncologic outcomes are favorable for this group. No clinicopathologic features are significant for DFS within pathologic stage I. LEVEL OF EVIDENCE: 2b. Laryngoscope, 128:1133-1139, 2018. PMID- 28990701 TI - Survey on attitudes towards renaming bipolar disorder in Japanese. PMID- 28990702 TI - Prevalence and associated factors of impaired renal function in Chinese children: the China Health and Nutrition Survey. AB - AIM: To assess the prevalence of impaired renal function and its associated factors in Chinese children. METHODS: Children aged 7-18 years in China Health and Nutrition Survey (CHNS) 2009 were included as participants, and their anthropometric measurements, blood pressure (BP) and biochemical parameters were taken for analysis. The estimated glomerular filtration rate (eGFR) was calculated by using the Schwartz "original" formula. RESULTS: The prevalence of estimated glomerular filtration rate (eGFR) < 90 ml/min/1.73 m2 and < 75 ml/min/1.73 m2 was 10.09% (95% CI: 8.03-12.11) and 1.01% (95% CI: 0.38-1.77) respectively. The prevalence of impaired renal function (eGFR < 60 ml/min/1.73 m2 ) was 0.25%. Age was detected as a negative associated factor whereas hyperuricemia and elevated total cholesterol (TC) were positively associated factors for subjects with eGFR < 90 ml/min/1.73 m2 . In the group of eGFR < 75 ml/min/1.73 m2 , only elevated TC was related to the increased odds of decreased eGFR. CONCLUSIONS: Our findings underscore the need for large-scale programs to detect and treat the early-stage impaired renal function in the paediatric population in China. PMID- 28990703 TI - Effects of maternal separation and antidepressant drug on epigenetic regulation of the brain-derived neurotrophic factor exon I promoter in the adult rat hippocampus. AB - AIM: Early life stress can induce epigenetic changes through genetic and environmental interactions and is a risk factor for depression. Brain-derived neurotrophic factor (BDNF) has been implicated in the pathophysiology of depression and antidepressant drug action. We investigated epigenetic changes at the BDNF exon I promoter in the hippocampus of adult rats subjected to maternal separation (MS) during early life and treated with an antidepressant drug as adults. METHODS: Rat pups were subjected to MS from postnatal day 1 to 21 and received chronic escitalopram (ESC) as adults. We assessed the effects of MS and ESC on BDNF exon I and DNA methyltransferases (DNMT) mRNA levels (quantitative reverse-transcription polymerase chain reaction), acetylated histone H3, and MeCP2 binding to the BDNF promoter I (chromatin immunoprecipitation followed by real-time polymerase chain reaction), and BDNF protein levels (enzyme-linked immunosorbent assay). RESULTS: The levels of BDNF protein, exon I mRNA, histone H3 acetylation, and DNMT1 and DNMT3a mRNA were altered in the MS group compared with the control group. Significant decreases were observed in the BDNF protein, exon I mRNA, and histone H3 acetylation levels and there were significant increases in DNMT1 and DNMT3a mRNA levels. The comparison between the MS + ESC and MS groups revealed significant increases in BDNF protein, exon I mRNA, and histone H3 acetylation levels and significant decreases in MeCP2 and DNMT1 and DNMT3a mRNA levels. CONCLUSION: These findings indicate that MS induced epigenetic changes at the BDNF exon I promoter and these changes were prevented by antidepressant drug treatment during adulthood. PMID- 28990704 TI - Epithelioid glioblastomas stratify into established diagnostic subsets upon integrated molecular analysis. AB - Epithelioid glioblastoma (eGBM) is a newly defined and rare GBM variant in the current WHO 2016 classification. BRAF V600E mutation is overrepresented in these tumors and there is known some morphological overlap with anaplastic epithelioid PXA (ePXA). In order to further elucidate this diagnostic category, we molecularly characterized 64 pediatric and adult examples initially diagnosed as "eGBM." Tumors were analyzed using array based methylation and direct sequencing of the BRAF and TERT genes. Our results demonstrated considerable molecular and clinical heterogeneity among eGBM cohort. Methylation patterns, copy number alterations, and mutational analysis data, in combination with clinical findings disclosed three different, well established tumor subtypes: (i) PXA-like tumors with favorable prognosis, predominantly in children and young adults (38), (ii) IDHwt GBM-like tumors with poor prognosis, mainly occurring in older adults, albeit with more frequent BRAF mutations (17), and (iii) RTK1 pediatric GBM-like neoplasms of intermediate prognosis in children and young adults, associated with chromothripsis and frequent PDGFRA amplifications (9). We conclude that the histopathologically defined eGBM do not represent a single diagnostic entity, but rather at least three molecularly and biologically distinct categories. Therefore, additional molecular testing through genome-wide molecular profiling is recommended to further stratify these rare cases. PMID- 28990705 TI - An Enzymatic Route to alpha-Tocopherol Synthons: Aromatic Hydroxylation of Pseudocumene and Mesitylene with P450 BM3. AB - Aromatic hydroxylation of pseudocumene (1 a) and mesitylene (1 b) with P450 BM3 yields key phenolic building blocks for alpha-tocopherol synthesis. The P450 BM3 wild-type (WT) catalyzed selective aromatic hydroxylation of 1 b (94 %), whereas 1 a was hydroxylated to a large extent on benzylic positions (46-64 %). Site saturation mutagenesis generated a new P450 BM3 mutant, herein named "variant M3" (R47S, Y51W, A330F, I401M), with significantly increased coupling efficiency (3- to 8-fold) and activity (75- to 230-fold) for the conversion of 1 a and 1 b. Additional pi-pi interactions introduced by mutation A330F improved not only productivity and coupling efficiency, but also selectivity toward aromatic hydroxylation of 1 a (61 to 75 %). Under continuous nicotinamide adenine dinucleotide phosphate recycling, the novel P450 BM3 variant M3 was able to produce the key tocopherol precursor trimethylhydroquinone (3 a; 35 % selectivity; 0.18 mg mL-1 ) directly from 1 a. In the case of 1 b, overoxidation leads to dearomatization and the formation of a valuable p-quinol synthon that can directly serve as an educt for the synthesis of 3 a. Detailed product pattern analysis, substrate docking, and mechanistic considerations support the hypothesis that 1 a binds in an inverted orientation in the active site of P450 BM3 WT, relative to P450 BM3 variant M3, to allow this change in chemoselectivity. This study provides an enzymatic route to key phenolic synthons for alpha-tocopherols and the first catalytic and mechanistic insights into direct aromatic hydroxylation and dearomatization of trimethylbenzenes with O2 . PMID- 28990706 TI - Effect of dietary supplementation of organic zinc on laying performance, egg quality and some biochemical parameters of laying hens. AB - This study was conducted to evaluate the effects of zinc methionine (Zn-Met) supplementation on the performance, egg quality, antioxidant status and some biochemical parameters of blood serum in laying hens from 22 to 34 weeks of age. A total of 120 Hisex Brown laying hens of 22-week-old were randomly allocated into five treatments with six cage replicates for each (four hens/replicate). Dietary treatments consisted of the basal diet with no Zn-Met supplementation (control group) and basal diet supplemented with 25, 50, 75 or 100 mg Zn-Met/kg diet. No significant differences were observed on body weight, body weight gain or feed conversion ratio due to dietary Zn-Met supplementation. However, highly significant impact was observed on daily feed intake. Egg number, egg weight and egg mass were increased in the group fed diet supplemented with the highest level of Zn-Met (100 mg/kg of diet) as compared to other groups. All egg quality traits were statistically (p > .05 or .01) affected as a response to dietary Zn-Met supplementation except egg shape index, shell percentage and yolk index. In comparison with the control group, dietary supplementation of 25, 50, 75 or 100 mg Zn-Met/kg decreased serum triglyceride and LDL-cholesterol levels. Serum cholesterol level was increased with all dietary levels of Zn-Met in comparison with the control group. Dietary Zn-Met supplementation increased the serum content of zinc, where the highest values were recorded with 50 and 100 mg Zn Met/kg diet. Dietary Zn-Met levels did not affect the antioxidant indices in blood serum except for the activity of copper-zinc superoxide dismutase (Cu-Zn SOD). The activity of Cu-Zn-SOD was increased with Zn-Met supplementations with no differences among supplemental zinc levels. It is concluded that dietary Zn Met supplementation reduced serum triglyceride, LDL-cholesterol and increased Zn status and resulted in promoting antioxidant ability of laying hens, and the addition of 100 mg Zn-Met/kg to layer diet was appropriate for improving the above parameters in addition to egg production indices and Haugh unit score. PMID- 28990707 TI - Rapid changes in brain aromatase activity in the female quail brain following expression of sexual behaviour. AB - In male quail, oestrogens produced in the brain (neuro-oestrogens) exert a dual action on male sexual behaviour: they increase sexual motivation within minutes via mechanisms activated at the membrane but facilitate sexual performance by slower, presumably nuclear-initiated, mechanisms. Recent work indicates that neuro-oestrogens are also implicated in the control of female sexual motivation despite the presence of high circulating concentrations of oestrogens of ovarian origin. Interestingly, aromatase activity (AA) in the male brain is regulated in time domains corresponding to the slow "genomic" and faster "nongenomic" modes of action of oestrogens. Furthermore, rapid changes in brain AA are observed in males after sexual interactions with a female. In the present study, we investigated whether similar rapid changes in brain AA are observed in females allowed to interact sexually with males. A significant decrease in AA was observed in the medial preoptic nucleus after interactions that lasted 2, 5 or 10 minutes, although this decrease was no longer significant after 15 minutes of interaction. In the bed nucleus of the stria terminalis, a progressive decline of average AA was observed between 2 and 15 minutes, although it never reached statistical significance. AA in this nucleus was, however, negatively correlated with the sexual receptivity of the female. These data indicate that sexual interactions affect brain AA in females as in males in an anatomically specific manner and suggest that rapid changes in brain oestrogens production could also modulate female sexual behaviour. PMID- 28990708 TI - Astroblastoma: a distinct tumor entity characterized by alterations of the X chromosome and MN1 rearrangement. AB - Astroblastoma is a rare, enigmatic tumor of the central nervous system (CNS) which shares some clinicopathologic aspects with other CNS tumors, especially ependymoma. To further clarify the nature of astroblastoma, we performed clinicopathologic and molecular genetic studies on eight cases of astroblastoma. The median age of the patients was 14.5 years, ranging from 5 to 60 years, and seven of the patients were female. All tumors arose in the cerebral hemisphere and radiologically appeared to be well-bordered, nodular tumors often associated with cystic areas and contrast-enhancement. Six of the seven patients with prognosis data survived without recurrences during the follow-up periods ranging from six to 76 months. One patient had multiple recurrences and died six years later. All tumors exhibited salient microscopic features, such as being well demarcated from the surrounding brain tissue, perivascular arrangement of epithelioid tumor cells (represented by "astroblastic" pseudorosettes, trabecular alignment, and pseudopapillary patterns), and hyalinized blood vessels. Immunoreactivity for GFAP, S-100 protein, Olig2, and EMA was variably demonstrated in all tumors, and IDH1 R132H and L1CAM were negative. Array comparative genomic hybridization revealed numerous heterozygous deletions on chromosome X in the four tumors studied, and break-apart fluorescence in situ hybridization demonstrated rearrangement of MN1 in five tumors with successful testing. The characteristic clinicopathologic and genetic findings support the idea that astroblastoma is distinct from other CNS tumors, in particular, ependymoma. In addition, MN1 rearrangement and aberrations of chromosome X may partly be involved in the pathogenesis of astroblastoma. PMID- 28990709 TI - Study of morphological and mechanical features of multinuclear and mononuclear SW480 cells by atomic force microscopy. AB - This article studies the morphological and mechanical features of multinuclear and mononuclear SW480 colon cancer cells by atomic force microscopy to understand their drug-resistance. The SW480 cells were incubated with the fullerenol concentrations of 1 mg/ml and 2 mg/ml. Morphological and mechanical features including the height, length, width, roughness, adhesion force and Young's modulus of three multinuclear cell groups and three mononuclear cell groups were imaged and analyzed. It was observed that the features of multinuclear cancer cells and mononuclear cancer cells were significantly different after the treatment with fullerenol. The experiment results indicated that the mononuclear SW480 cells were more sensitive to fullerenol than the multinuclear SW480 cells, and the multinuclear SW480 cells exhibited a stronger drug-resistance than the mononuclear SW480 cells. This work provides a guideline for the treatments of multinuclear and mononuclear cancer cells with drugs. PMID- 28990710 TI - Dr. Takuya Ueno to Serve as a Co-Editor of Transplantation for Artificial Organs. PMID- 28990713 TI - Welcome to "24 +1 = 25" the Quarter Century Anniversary Meeting of Our Society: Evolving to the International Society for Mechanical Circulatory Support. PMID- 28990711 TI - Tsunamasa Inou: A Pioneer in Artificial Organs and Transplantation in Japan. PMID- 28990714 TI - Challenges in Assist Devices Therapy in the Middle East. PMID- 28990715 TI - Congress Summary: The 24th Congress of the International Society for Rotary Blood Pumps. PMID- 28990716 TI - Genome-wide characterization of Phytophthora infestans metabolism: a systems biology approach. AB - Genome-scale metabolic models (GEMs) provide a functional view of the complex network of biochemical reactions in the living cell. Initially mainly applied to reconstruct the metabolism of model organisms, the availability of increasingly sophisticated reconstruction methods and more extensive biochemical databases now make it possible to reconstruct GEMs for less well-characterized organisms, and have the potential to unravel the metabolism in pathogen-host systems. Here, we present a GEM for the oomycete plant pathogen Phytophthora infestans as a first step towards an integrative model with its host. We predict the biochemical reactions in different cellular compartments and investigate the gene-protein reaction associations in this model to obtain an impression of the biochemical capabilities of P. infestans. Furthermore, we generate life stage-specific models to place the transcriptomic changes of the genes encoding metabolic enzymes into a functional context. In sporangia and zoospores, there is an overall down regulation, most strikingly reflected in the fatty acid biosynthesis pathway. To investigate the robustness of the GEM, we simulate gene deletions to predict which enzymes are essential for in vitro growth. This model is an essential first step towards an understanding of P. infestans and its interactions with plants as a system, which will help to formulate new hypotheses on infection mechanisms and disease prevention. PMID- 28990717 TI - Mechanisms of resistance in the rice cultivar Manikpukha to the rice stem nematode Ditylenchus angustus. AB - The incompatible interaction between the rice cultivar Manikpukha and the rice stem nematode Ditylenchus angustus has been reported recently. This research focuses on the underlying mechanisms of resistance in Manikpukha. Invasion, post infection development and reproduction of D. angustus were compared in compatible and incompatible interactions to identify the stage in which resistance occurs. The results indicate that resistance in Manikpukha is associated with reduced development and reproduction, implying that resistance acts post-invasion. We studied the possible involvement of three classical defence hormones, salicylic acid (SA), jasmonic acid (JA) and ethylene (ET), in response to infection in a compatible interaction using biosynthesis/signalling-deficient transgenic rice lines. All three hormones appear to have an influence on the basal defence of Nipponbare against the stem nematode. Although hormone application increases basal defences, expression studies and hormone analyses after nematode infection in Manikpukha did not show a clear involvement of the hormone defense pathways for SA, ET and JA. However, it seems that OsPAL1 plays a pivotal role in resistance, indicating that the phenylpropanoid pathway and its products might be key players in the incompatible interaction. Lignin measurement showed that, although basal levels are similar, Manikpukha had a significantly higher lignin content on nematode infection, whereas it was decreased in the susceptible cultivar. The results presented here show that SA, ET and JA are involved in basal defences, but the resistance of Manikpukha against D. angustus probably relies on products of the phenylpropanoid pathway. PMID- 28990718 TI - Limb-sparing sarcoma reconstruction with functional composite thigh flaps. AB - INTRODUCTION: Innervated muscle transfer can improve functional outcomes after extensive limb-sparing sarcoma resections. We report our experience using composite thigh flaps for functional reconstruction of large oncologic extremity defects. PATIENTS AND METHODS: Between 2011 and 2014, four limb-sparing oncologic resections (3 lower extremities, 1 upper extremity) underwent immediate functional reconstruction with composite thigh free flaps in three males and one female. The age of the patients ranged from 36 to 73 years. There were 3 soft tissue sarcomas and one giant cell tumor, all required resection of entire muscle compartments. Flap components included fasciocutaneous tissue with sensory nerve, plicated iliotibial band (ITB), and variable amounts of motorized vastus lateralis (VL). RESULTS: All flaps survived without complications. All patients showed VL motor innervation by six months. Follow-up ranged from 20 to 36 months. Motor strength ranged from 2 to 5 out of 5, active range of motion was 25-92% of normal, and Musculoskeletal Tumor Society (MSTS) Scores were between 22 and 29 out of 30. CONCLUSIONS: Limb-sparing techniques for upper and lower extremity sarcomas continue to evolve. Our experience has validated the composite thigh free flap as an excellent option for one-stage functional reconstruction of large limb defects. PMID- 28990719 TI - Japanese Outreach Model Project for patients who have difficulty maintaining contact with mental health services: Comparison of care between higher functioning and lower-functioning groups. AB - AIM: The Japanese Ministry of Health, Labor and Welfare sponsored the current examination of a new community mental health service, the Japan Outreach Model Project (JOMP), for persons with mental illnesses and who find it difficult to continue with ongoing treatment. Shorter readmission rates and hospital stays were found. In this study, the amount and type of care that were delivered by the JOMP were examined in order to inform the process of establishing the public insurance system. METHODS: The data were collected from 32 JOMP outreach teams from 21 prefectures in Japan that agreed to participate; 415 patients were included in the analysis. The clients' characteristics, social functions, problematic behavior score, and the amount and type of care that were delivered were examined. RESULTS: Higher amounts of care were delivered in the first month, compared to the remaining months, and the care was relatively stable from months 2-5. This suggests that consistently high care was needed for the JOMP clients who found it difficult to maintain contact with mental health services. Those clients with an increased overall global assessment functioning score at 6 months (n = 151) had received significantly more care than those whose functioning had decreased or remained stable (n = 150). The types of increased care that were provided to the higher functioning group were: "assistance with daily living tasks," "medical support for psychiatric symptoms," "empowering the client," "communication and coordination," "support for physical health," and "vocational and educational support." CONCLUSION: The type and amount of care can positively influence good functional outcomes for those in the community who find it difficult to maintain contact with mental health services. PMID- 28990721 TI - Getting termination right: strategies for cervical preparation. PMID- 28990720 TI - Autotransplantation of teeth to the anterior maxilla: A systematic review of survival and success, aesthetic presentation and patient-reported outcome. AB - BACKGROUND/AIM: Autotransplantation of teeth to the anterior maxilla may be indicated after trauma or in patients with congenitally missing teeth. The aim of this systematic review was to report the current evidence concerning survival and success rate, aesthetic outcome, and patient-reported outcome of autotransplanted teeth to the anterior maxilla. MATERIALS AND METHODS: A MEDLINE search followed by an additional hand search was performed to identify relevant literature. All levels of evidence except case reports were considered. Any publication reporting on 10 or more autotransplanted teeth to the anterior maxilla, and written in English were eligible for this systematic review. RESULTS: The systematic search identified 95 abstracts. Thirty-seven full-text articles were evaluated of which 17 could finally be included. Data on survival and success rate of the transplants could be extracted from 11 studies. Survival rates ranged between 93% and 100% (weighted mean: 96.7%, median: 100%) after 9 months to 22 years of observation (median: 8.75 years). No consensus regarding definition of success criteria of the transplants could be found in the literature. Two and four studies contained data on aesthetic and patient-reported outcomes, respectively. In general, they reported favourable aesthetic results and high patient satisfaction. CONCLUSION: The current available evidence suggests a high survival rate after autotransplantation of teeth to the anterior maxilla. However, the level of evidence is low. Limited data on aesthetic and patient-reported outcomes warrant additional research in this field. PMID- 28990722 TI - Disruption of calcineurin catalytic subunit (cnaA) in Epichloe festucae induces symbiotic defects and intrahyphal hyphae formation. AB - Calcineurin is a conserved calcium/calmodulin-dependent protein phosphatase, consisting of a catalytic subunit A and a regulatory subunit B, which is involved in calcium-dependent signalling and regulation of various important cellular processes. In this study, we functionally characterized the catalytic subunit A (CnaA) of the endophytic fungus Epichloe festucae which forms a symbiotic association with the grass host Lolium perenne. We deleted the CnaA-encoding gene cnaA in E. festucae and examined its role in hyphal growth, cell wall integrity and symbiosis. This DeltacnaA strain had a severe growth defect with loss of radial growth and hyper-branched hyphae. Transmission electron microscopy and confocal microscopy analysis of the mutant revealed cell wall defects, aberrant septation and the formation of intrahyphal hyphae, both in culture and in planta. The mutant strain also showed a reduced infection rate in planta. The fluorescence of mutant hyphae stained with WGA-AF488 was reduced, indicating reduced chitin accessibility. Together, these results show that E. festucae CnaA is required for fungal growth, maintaining cell wall integrity and host colonization. PMID- 28990723 TI - MRI findings in deep infiltrating endometriosis: A pictorial essay. AB - Endometriosis is an important gynaecological disorder which can impact significantly on an individual's quality of life and has major implications on fertility. Deep infiltrating endometriosis is a severe form of endometriosis which can cause obliteration of anatomic compartments. Laparoscopy remains the gold standard for diagnosis of endometriosis, although is an invasive procedure that has the potential to be hindered by obliterative disease. Ultrasound is often employed as the first-line imaging modality when endometriosis is suspected, however, MRI is more accurate in assessment of complex disease. Pre operative MRI is highly specific in the diagnosis of endometriosis and characterization of disease extent, and plays a key role in guiding surgical management. MRI findings in deep infiltrating endometriosis are described. PMID- 28990724 TI - Preparation and Thermal Properties of Polycarbonates/esters Catalyzed by Using Dinuclear Salph-Al from Ring-Opening Polymerization of Epoxide Monomers. AB - A dinuclear Salph-Al complex/bis(triphenylphosphine)iminium chloride catalyst system was synthesized and employed for cyclohexene oxide (CHO) and CO2 copolymerization. The catalyst system had an excellent selectivity of 99 % for carbonate linkages and the resultant poly(cyclohexene carbonate) (PCHC) had a high glass transition temperature (Tg ) of 123.8 degrees C and a thermal decomposition temperature (5 % weight loss; Td 5 % ) of 265 degrees C. Furthermore, this catalyst system was active in the polymerization of phthalic anhydride (PA) and epoxides. Poly(CHO-alt-PA) was completely alternating, and had improved thermal properties (Tg =142.7 and Td 5 % =295 degrees C) compared with PCHC. The Tg values of the polyesters could be adjusted by addition of PO to the CHO/PA reaction system. For the CHO/PO/PA terpolymerization, CHO and PO participated concurrently and proportionally in the chain growth and the obtained terpolyesters had tunable Tg values from 62.8 to 142.7 degrees C depending on the CHO/PO feed ratio. PMID- 28990725 TI - Single-Molecule Monitoring of the Structural Switching Dynamics of Nucleic Acids through Controlling Fluorescence Blinking. AB - Single-molecule fluorescence resonance energy transfer (smFRET) is a powerful tool to investigate the dynamics of biomolecular events in real time. However, it requires two fluorophores and can be applied only to dynamics that accompany large changes in distance between the molecules. Herein, we introduce a method for kinetic analysis based on control of fluorescence blinking (KACB), a general approach to investigate the dynamics of biomolecules by using a single fluorophore. By controlling the kinetics of the redox reaction the blinking kinetics or pattern can be controlled to be affected by microenvironmental changes around a fluorophore (rKACB), thereby enabling real-time single-molecule measurement of the structure-changing dynamics of nucleic acids. PMID- 28990727 TI - Magnetic resonance imaging of the prostate and targeted biopsy, Comparison of PIRADS and Gleason grading. AB - INTRODUCTION: Multiparametric magnetic resonance imaging (mpMRI) of the prostate has become integral in the investigation of suspected prostate cancer. Regions of interest are graded using the PIRADS scoring system, and in our institution, lesions graded as PIRADS 3-5 undergo sampling by MRI-guided biopsy. Limited data currently exists on PIRADS grading and biopsy results. METHODS: Retrospective review of 343 MRI-guided biopsies (MRGB) performed between April 2013 and December 2016 was conducted. This included patients irrespective of whether they were biopsy naive, biopsy negative or known low-grade malignancy. A Gleason score (G) >= 3+4 was considered to reflect clinically significant disease (CSD). RESULTS: Of the 18 PIRADS 2 cases (at referrer request) who went to biopsy, 16 were negative and two had small volume Gleason 6 cancer. A total of 75 PIRADS 3 cases were biopsied with 88% negative or small volume Gleason 6 cancer, only 12% yielded >= G 3+4. Of the 133 PIRADS 4 lesions, 24% were negative, 25% were G6 and 51% were >= G 3+4. A total of 117 PIRADS 5 cases were biopsied with 7% negative, 13% Gleason 6 and 80% considered significant (>= G 3+4). Of all biopsies, 230 (67%) had a positive result (>= G6) with 171 of these (75%) being considered CSD, with overall CSD of 50% (171/343). CONCLUSIONS: This paper demonstrates the incidence of CSD for different PIRADS grades. The low incidence of CSD in PIRADS 3 lesions suggests that in low clinical risk men, follow up in priority to biopsy may be an alternative treatment pathway. PMID- 28990726 TI - Multiple mechanisms of dimethyl fumarate in amyloid beta-induced neurotoxicity in human neuronal cells. AB - Alzheimer disease (AD) is characterized by a complex heterogeneity of pathological changes, and any therapeutic approach categorically requires a multi targeted way. It has been demonstrated that together with the hallmarks of the disease such as neurofibrillary tangles and senile plaques, oxidative and inflammatory stress covered an important role. Dimethyl fumarate (DMF) is an orally bioavailable methyl ester of fumaric acid and activator of Nrf2 with potential neuroprotective and immunomodulating activities. Therefore, the aim of the present work was to evaluate the potential beneficial effects of DMF, compared with its active metabolite monomethyl fumarate (MMF) (both at 30 MUM) in an in vitro Alzheimer's model using SH-SY5Y human neuroblastoma cell lines stimulated with amyloid-beta (Abeta). Moreover, the effect of DMF, compared with MMF, was evaluate by an ex vivo model using organotypic hippocampal slice cultures stimulated with Abeta1-42 (1 MUg/ml), to better understand its action in a pathological setting. In both models, DMF pre-treatment (30 MUM) preserved cellular viability from Abeta stimulation, reducing tau hyper-phosphorylation, much more efficiently then MMF (30 MUM). Moreover, DMF was able to induce an activation of manganese superoxide dismutase (MnSOD) and heme-oxygenase-1 (HO-1), decreasing the severity of oxidative stress. Our results showed important multi protective effects of DMF pre-treatment from Abeta stimulation both in in vitro and ex vivo models, highlighting an Nrf2/NF-kappaB-dependent mechanism, which could provide a valuable support to the therapies for neurodegenerative diseases today. PMID- 28990728 TI - Female bladder outlet obstruction: Common symptoms masking an uncommon cause. AB - OBJECTIVE: Bladder outlet obstruction (BOO) in women remains an underdiagnosed condition. Although diagnosed rarely in general urologic practice, its incidence in specialist centers has been reported to be up to 29%. In the present study we evaluated the incidence of female BOO in adult women referred for evaluation of lower urinary tract symptoms or urinary incontinence, assessing its etiology and correlating this with its clinical presentation. METHODS: The present study consisted of a retrospective review of a prospectively acquired videourodynamic database of 1142 consecutive women referred for evaluation of lower urinary tract symptoms (LUTS) or urinary incontinence from March 2007 to December 2012 and diagnosed with BOO. After exclusions, data from 1014 patients were analyzed. BOO was defined using a combination of radiographic evidence of obstruction during the voiding phase of the urodynamic study and pressure-flow criteria (Solomon Greenwell nomogram). Diagnosis was confirmed by cystoscopy, maximal urethral closure pressure, and magnetic resonance imaging as clinically indicated. RESULTS: In all, 192 women (19%) were diagnosed with BOO. Functional sphincteric obstruction was diagnosed in 70 women (36%). The most common anatomical cause of BOO was previous anti-incontinence surgery, followed by urethral stricture, diagnosed in 21% and 20% of patients, respectively. The most common presenting symptoms were storage phase symptoms of daytime and night-time urinary frequency. CONCLUSIONS: BOO was present in 19% of women with LUTS. Functional sphincteric obstruction was the most common cause (36%), followed by obstruction after anti incontinence surgery (21%). The most common presenting symptom was daytime urinary frequency. BOO should be suspected in women with refractory LUTS, especially those presenting with urinary frequency. PMID- 28990730 TI - Corrigendum. PMID- 28990729 TI - Renoprotective effects of topiroxostat for Hyperuricaemic patients with overt diabetic nephropathy study (ETUDE study): A prospective, randomized, multicentre clinical trial. AB - AIM: We aimed to evaluate the anti-albuminuric effects of topiroxostat in Japanese hyperuricaemic patients with diabetic nephropathy. METHODS: In this 24 week, multicentre, open-label, randomized (1 : 1) trial, we assigned hyperuricaemic patients with diabetic nephropathy (estimated glomerular filtration rate >= 20 mL/min per 1.73m2 ) and overt proteinuria (0.3 <= urine protein to creatinine ratio (UPCR) <3.5 g/g Cr) to either high dose (160 mg daily) or low dose (40 mg daily) topiroxostat. The primary endpoint was the change in albuminuria indicated by urine albumin-to-creatinine ratio (UACR) from the baseline at the final time point. RESULTS: A total of 80 patients underwent randomization. The changes in UACR after 24 weeks of treatment (or at the final time point if patients failed to reach 24 weeks) relative to the baseline were 122 mg/gCr (95% CI: -5.1 to -240.1, P = 0.041) in patients treated with high dose, while treatment with low dose topiroxostat could not show significant reduction (P = 0.067). In the linear mixed model including baseline albuminuria, eGFR, age, and sex as covariates, the decreases in UACR were still significant from baseline to 12 weeks by 228.7 +/- 83.2 mg/gCr (P = 0.0075) in the high dose group. The adverse-event profile during this study was not different between the groups. CONCLUSION: Topiroxostat 160 mg daily reduced albuminuria in patients with diabetic nephropathy. (Funded by Sanwa Kagaku Kenkyusho; Trial registration, UMIN000015403). PMID- 28990731 TI - Comment on a paper by Dupoiron et al. "A phase III randomized controlled study on the efficacy and improved bowel function of prolonged-release (PR) oxycodone- naloxone (up to 160/80 mg daily) versus oxycodone PR". PMID- 28990732 TI - First use of Micro Vascular Plugs in Australia: Endovascular treatment of pulmonary arteriovenous malformation. AB - This report describes the first Australian experience with the Micro Vascular Plug System (MVP), as a permanent embolic device for the treatment of pulmonary arteriovenous malformations (PAVMs). MVPs deployed in small vessels between 2 mm and 5 mm are demonstrated to be feasible, safe and effective treatment for PAVMs. PMID- 28990733 TI - Sustainable and Continuous Synthesis of Enantiopure l-Amino Acids by Using a Versatile Immobilised Multienzyme System. AB - The enzymatic synthesis of alpha-amino acids is a sustainable and efficient alternative to chemical processes, through which achieving enantiopure products is difficult. To more address this synthesis efficiently, a hierarchical architecture that irreversibly co-immobilises an amino acid dehydrogenase with polyethyleneimine on porous agarose beads has been designed and fabricated. The cationic polymer acts as an irreversible anchoring layer for the formate dehydrogenase. In this architecture, the two enzymes and polymer colocalise across the whole microstructure of the porous carrier. This multifunctional heterogeneous biocatalyst was kinetically characterised and applied to the enantioselective synthesis of a variety of canonical and noncanonical alpha-amino acids in both discontinuous (batch) and continuous modes. The co-immobilised bienzymatic system conserves more than 50 % of its initial effectiveness after five batch cycles and 8 days of continuous operation. Additionally, the environmental impact of this process has been semiquantitatively calculated and compared with the state of the art. PMID- 28990734 TI - Application of the allogenic mesenchymal stem cells in the therapy of the bladder tuberculosis. AB - Urogenital tuberculosis (TB) often leads to contraction of the bladder, a reduction of the urinary reservoir capacity, and, in the latest stage, to real microcystitis up to full obliteration. Bladder TB Stage 4 is unsuitable for conservative therapy, and cystectomy with subsequent enteroplasty is indicated. In this study, using a model of bladder TB in New Zealand rabbits, the therapeutic efficacy of the interstitial injection of autologous bone-derived mesenchymal stem cells (MSCs) combined with standard anti-TB treatment in the restoration of the bladder function was demonstrated. For analysis of the MSC distribution in tissues, the latter were labelled with superparamagnetic iron oxide nanoparticles. In vitro studies demonstrated the high intracellular incorporation of nanoparticles and the absence of cytotoxicity on MSC viability and proliferation. A single-dose administration of MSCs into the bladder mucosal layer significantly reduced the wall deformation and inflammation and hindered the development of fibrosis, which was proven by the subsequent histological assay. Confocal microscopy studies of the bladder cryosections confirmed the presence of superparamagnetic iron oxide nanoparticle-labelled MSCs in different bladder layers of the treated animals, thus indicating the role of stem cells in bladder regeneration. PMID- 28990735 TI - Metabolism in cancer metastasis: bioenergetics, biosynthesis, and beyond. AB - Metabolic changes accompany tumor progression and metastatic dissemination of cancer cells. Yet, until recently, metabolism has received little attention in the study of cancer metastasis. Cancer cells undergo significant metabolic rewiring as they acquire metastatic traits and adapt to survive in multiple environments with varying nutrient availability, oxygen concentrations, and extracellular signals. Therefore, to effectively treat metastatic cancer, it is important to understand the metabolic strategies adopted by cancer cells during the metastatic process. Here, we focus on the metabolic pathways known to play a role in cancer metastasis, including glycolysis, the pentose phosphate pathway, tricarboxylic acid cycle, oxidative phosphorylation, amino acid metabolism, and fatty acid metabolism. Recent studies have uncovered roles for these pathways in cellular events that promote metastasis, including reactive oxygen species mediated signaling, epigenetic regulation, and interaction with the extracellular matrix. We also discuss the metabolic interplay between immune cells and cancer cells supporting metastasis. Finally, we highlight the current limitations of our knowledge on this topic, and present future directions for the field. WIREs Syst Biol Med 2018, 10:e1406. doi: 10.1002/wsbm.1406 This article is categorized under: Biological Mechanisms > Metabolism. PMID- 28990736 TI - Hospital outcomes of transcatheter versus surgical aortic valve replacement in female in the United States. AB - OBJECTIVES: To assess the in-hospital mortality and complications in female between transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR). BACKGROUND: Female is one of the risk factors for increased adverse events in cardiac surgery. METHODS AND RESULTS: Nationwide Inpatient Sample database was queried from 2011 to 2014 for patients who underwent TAVR or SAVR in female patients. The primary endpoint was in-hospital all-cause mortality and second endpoints were perioperative complications. We performed a propensity score analysis to calculate the adjusted odds ratio (OR) for each outcome. Patients who had concomitant cardiac surgery and those who had TAVR or SAVR mainly for aortic regurgitation were excluded. Our query from 2011 to 2014 resulted in a total of 3,067 TAVR and 18,594 SAVR in female patients. TAVR patients were in general elder and had a higher burden of comorbidities. The primary endpoint was similar between TAVR and SAVR (4.2% vs. 3.9%, OR 1.0, P = 0.89). Compared to SAVR, female TAVR patients had less hemorrhage requiring transfusion (12% vs. 21%, OR 0.41, P < 0.001), perioperative cardiac arrest and nonfatal myocardial infarction (9.8% vs. 17%, OR 0.38, P < 0.001), respiratory complication (1.6% vs. 4.4%, OR 0.28, P < 0.001), post-op sepsis (1.7% vs. 2.9%, OR 0.65, P = 0.03), acute myocardial infarction (3.0% vs. 4.9%, OR 0.60, P < 0.001), and acute kidney injury (15% vs. 18%, OR 0.62, P < 0.001). Conversely, female TAVR patients had significantly increased risk of new pacemaker implantation (11% vs. 5.9%, OR 1.7, P < 0.001) and use of extracorporeal membrane oxygenation (0.66% vs. 0.24%, OR 2.8, P < 0.001). TAVR patients had less nonroutine discharge. The median hospital cost was significantly higher in TAVR than SAVR (median $51,274 vs. $43,677, P < 0.001) but the length of stay was shorter (mean 7.8 days vs. 10.5 days). CONCLUSIONS: TAVR may be a better option for those patients with underlying comorbidities that predispose them at higher risk for complications that was less observed in TAVR group. However, higher cost and increased risk of need for extracorporeal membrane oxygenation, although rare, should be taken into consideration upon deciding the optimal mode for aortic valve replacement. PMID- 28990737 TI - Evaluation of kidney motion with and without a pneumatic abdominal compression belt: Considerations for stereotactic radiotherapy. AB - INTRODUCTION: The optimal delivery of stereotactic radiotherapy for kidney tumours requires an effective motion management strategy. This study assessed the effectiveness of a pneumatic abdominal compression belt in reducing kidney motion during free breathing. METHODS: Thirteen patients, with four-dimensional computed tomography (4DCT) of the abdomen in free breathing with and without a pneumatic abdominal compression belt, were retrospectively reviewed. Points of Interest (POI) were placed on each kidney to determine the greatest magnitude of displacement in all directions. RESULTS: Without compression, all patients had >5.0 mm motion in the craniocaudal (CC) direction in at least one kidney. Median CC excursion of the left superior pole was reduced with compression from 8.0 mm (range 2.0 mm-18.0 mm) to 4.0 mm (range 2.0 mm-10.0 mm, P = 0.047) and right superior pole from 10.0 mm (range 4.0 mm-16.0 mm) to 6.0 mm (range 2.0 mm-10.0 mm, P=value 0.051). A benefit was less evident for the left and right inferior poles with median CC excursion of 6.0 mm versus 4.0 mm and 5.0 mm versus 4.0 mm without and with compression, respectively. Median displacement in the anteroposterior direction (<=3.2 mm) and lateral directions (<=1.3 mm) was similar for left and right kidneys and not significantly altered by compression. Overall, seven patients had kidney motion reduced by >5.0 mm with two reduced by 10.0 mm. CONCLUSION: A pneumatic abdominal compression belt reduced kidney motion by >5.0 mm in seven of thirteen patients. The relative benefit is patient and location specific and should be assessed on an individual basis. PMID- 28990738 TI - Treatment of obsessive morbid jealousy with cognitive analytic therapy: An adjudicated hermeneutic single-case efficacy design evaluation. AB - OBJECTIVE: The evidence base for the treatment of morbid jealousy with integrative therapies is thin. This study explored the efficacy of cognitive analytic therapy (CAT). DESIGN: An adjudicated hermeneutic single-case efficacy design evaluated the cognitive analytic treatment of a patient meeting diagnostic criteria for obsessive morbid jealousy. METHOD: A rich case record was developed using a matrix of nomothetic and ideographic quantitative and qualitative outcomes. This record was then debated by sceptic and affirmative research teams. Experienced psychotherapy researchers acted as judges, assessed the original case record, and heard the affirmative-versus-sceptic debate. Judges pronounced an opinion regarding the efficacy of the therapy. RESULTS: The efficacy of CAT was supported by all three judges. Each ruled that change had occurred due to the action of the therapy, beyond any level of reasonable doubt. CONCLUSIONS: This research demonstrates the potential usefulness of CAT in treating morbid jealousy and suggests that CAT is conceptually well suited. Suggestions for future clinical and research directions are provided. PRACTITIONER POINTS: The relational approach of CAT makes it a suitable therapy for morbid jealousy. The narrative reformulation component of CAT appears to facilitate early change in chronic jealousy patterns. It is helpful for therapists during sessions to use CAT theory to diagrammatically spell out the patterns maintaining jealousy. PMID- 28990739 TI - Advances in native high-performance liquid chromatography and intact mass spectrometry for the characterization of biopharmaceutical products. AB - The characterization of biotherapeutics represents a major analytical challenge. This review discusses the current state-of-the-art in analytical technologies to profile biopharma products under native conditions, i.e., the protein three dimensional conformation is maintained during liquid chromatographic analysis. Native liquid-chromatographic modes that are discussed include aqueous size exclusion chromatography, hydrophobic interaction chromatography, and ion exchange chromatography. Infusion conditions and the possibilities and limitations to hyphenate native liquid chromatography to mass spectrometry are discussed. Furthermore, the applicability of native liquid-chromatography methods and intact mass spectrometry analysis for the characterization of monoclonal antibodies and antibody-drug conjugates is discussed. PMID- 28990740 TI - Schedules of Controlled Substances: Removal of Naldemedine From Control. Final rule. AB - With the issuance of this final rule, the Drug Enforcement Administration removes the substance naldemedine (4R,4aS,7aR,12bS)-3-(cyclopropylmethyl)-4a,7,9 trihydroxy-N-(2-(3-phenyl-1,2,4-oxadiazol-5-yl)propan-2-yl)-2,3,4,4a,5,7a hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-6-carboxamide) including its salts from the schedules of the Controlled Substances Act. Prior to the effective date of this rule, naldemedine was a schedule II controlled substance because it can be derived from opium alkaloids. This action removes the regulatory controls and administrative, civil, and criminal sanctions applicable to controlled substances, including those specific to schedule II controlled substances, on persons who handle (manufacture, distribute, reverse distribute, dispense, conduct research, import, export, or conduct chemical analysis) or propose to handle naldemedine. PMID- 28990741 TI - Post-transplant diabetes: diagnosis and management. AB - Post-transplant diabetes mellitus (PTDM) is common after most types of solid organ transplantation, though the actual incidence is as yet unknown because of the use of different diagnostic criteria. PTDM is the result of individual risk factors as well as risk factors associated with the transplant itself, particularly immunosuppressants. Previously called New Onset Diabetes, in many cases inadequate screening for diabetes before transplant cannot assure that the diabetes is new after transplant. The most recent international consensus guidelines suggest diagnosis should be delayed until the patient is taking maintenance doses of immunosuppressants even if they require treatment in the immediate hospitalization. Criteria for diagnosis follow those of the American Diabetes Association and the World Health Organization, although hemoglobin A1C should not be used as the only screening test at least until one year after transplant because of its insensitivity for significant glucose intolerance in the transplant patient and setting. Management of PTDM is best done in a team setting, with an emphasis on glycemic control, dyslipidemia, and hypertension, and taking into consideration immunosuppressant regimens and potential drug side effects and interactions. While PTDM has been associated with changes in outcomes, these have and may continue to improve with improved diabetes care in and out of the hospital, and other changes in post-transplant care. PMID- 28990742 TI - Autoimmune endocrine diseases. AB - The endocrine system is interested by several autoimmune diseases, characterized by different impact and severity, according to the organs involved. Autoimmune thyroid disorders (i.e. Hashimoto's thyroiditis and Graves' disease) and type 1 diabetes mellitus are the most common autoimmune endocrine disorders, while hypophysitis, adrenalitis (90% of cases of primary hypocortisolism or Addison's disease), POF and hypoparathyroidism represent quite rare conditions. Autoimmune endocrine diseases can also coexist in the same individuals and cluster in families. Some of these associations are nosologically codified in the so-called autoimmune polyglandular syndromes, but autoimmune endocrinopathies can also be accompanied by other non-endocrine autoimmune disorders (i.e. connective tissue, skin or gastrointestinal diseases). Pathophysiology generally results from a complex interplay among genetic predisposition and environmental/endogenous factors. In the diagnostic process, measurement of organ-specific autoantibodies, both with a causative role or as an epiphenomenon, is often fundamental and integrates the assessment of hormone axes and the targeted imaging studies. PMID- 28990743 TI - Drug Pricing Program Ceiling Price and Manufacturer Civil Monetary Penalties Regulation. Final rule; further delay of effective date. AB - The Health Resources and Services Administration (HRSA) administers section 340B of the Public Health Service Act (PHSA), known as the "340B Drug Pricing Program" or the "340B Program." HRSA published a final rule on January 5, 2017, that set forth the calculation of the ceiling price and application of civil monetary penalties. The final rule applied to all drug manufacturers that are required to make their drugs available to covered entities under the 340B Program. On August 21, 2017, HHS solicited comments on further delaying the effective date of the January 5, 2017, final rule to July 1, 2018 (82 FR 39553). HHS proposed this action to allow a more deliberate process of considering alternative and supplemental regulatory provisions and to allow for sufficient time for additional rulemaking. After consideration of the comments received on the proposed rule, HHS is delaying the effective date of the January 5, 2017, final rule, to July 1, 2018. PMID- 28990744 TI - Phosphoprotein 1 (osteopontin) gene (rs4754) affects markers of subclinical atherosclerosis in patients with type 2 diabetes mellitus. AB - BACKGROUND: Our study was designed to test a possible association between polymorphisms of the SPP1 gene (rs4754, rs28357094) and markers of carotid atherosclerosis (CIMT, number of affected segments of carotid arteries, sum of plaque thickness, presence of carotid plaques, and presence of unstable carotid plaques) in subjects with T2DM. The second aim was to test the possible association between polymorphisms of the SPP1 gene (rs4754, rs28357094) and the progression of carotid atherosclerosis (CIMT progression, change in total plaque thickness, change in the number of sites with plaques) in subjects with T2DM. METHODS: In the prospective study 595 T2DM subjects were enrolled. Markers of carotid atherosclerosis were assessed ultrasonographically. rs4754 and rs28357094 polymorphisms of the phosphoprotein 1 (SPP1) gene were determined with real-time PCR. RESULTS: In our study we found an association between SPP1 rs4754 and the presence of plaques at the time of recruitment, whereas we did not find any association between SPP1 rs28357094 and subclinical markers of carotid atherosclerosis at the time of recruitment. Moreover, we did not find any statistically significant effect of either rs4754 or rs28357094 on subclinical markers of carotid atherosclerosis progression (CIMT progression, change in total plaque thickness, change in the number of sites with plaques). As shown by the multiple linear regression analysis, genotypes of either rs4754 or rs28357094 did not have a statistically significant effect on the progression of subclinical markers of carotid atherosclerosis (CIMT progression, change in total plaque thickness, change in the number of sites with plaques) after the adjustment for confounding variables. CONCLUSIONS: We demonstrated an important effect of the SPP1 rs4754 on subclinical markers of carotid atherosclerosis in subjects with T2DM; however, as demonstrated by the multiple linear regression analysis, neither rs4754 nor rs28357094 had an important impact on the progression of subclinical markers of carotid atherosclerosis in subjects with T2DM. PMID- 28990745 TI - Diagnostic value of circulating microRNA-27a/b in patients with acute pulmonary embolism. AB - BACKGROUND: Circulating microRNAs (miRNAs) have been increasingly suggested as biomarkers for numerous diseases. The aims of this study were to evaluate the expression of plasma miR-27a/b in patients with acute pulmonary embolism (APE) and determine the possibility of miR-27a/b as diagnostic biomarkers for APE. METHODS: Seventy-eight APE patients diagnosed by computed tomographic pulmonary angiography (CTPA) and 70 age and gender matched normal volunteers were included in this study. The levels of miR-27a and miR-27b were measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and the concentrations of plasma D-dimer were measured using immunoturbidimetric assay. RESULTS: The levels of plasma miR-27a and miR-27b were significantly higher in APE patients (P<0.001) compared with normal controls. Receiver operating characteristic (ROC) curve analyses showed that plasma miR-27a was superior to miR-27b for the diagnosis of APE (AUC=0.784, AUC=0.707, respectively). Combining miR-27a or miR 27b with D-dimer significantly increased the diagnostic capacity of APE. CONCLUSIONS: Our results showed that circulating miR-27a and miR-27b might be potential novel diagnostic biomarkers in APE patients. PMID- 28990746 TI - Medical Devices; Gastroenterology-Urology Devices; Classification of the High Intensity Ultrasound System for Prostate Tissue Ablation. Final order. AB - The Food and Drug Administration (FDA or we) is classifying the high intensity ultrasound system for prostate tissue ablation into class II (special controls). The special controls that apply to the device type are identified in this order and will be part of the codified language for the high intensity ultrasound system forprostate tissue ablation's classification. We are taking this action because we have determined that classifying the device into class II (special controls) will provide a reasonable assurance of safety and effectiveness of the device. We believe this action will also enhance patients' access to beneficial innovativedevices, in part by reducing regulatory burdens. PMID- 28990747 TI - Paying for Prescription Drugs Around the World: Why Is the U.S. an Outlier? AB - Issue: Compared with other high-income countries, the United States spends the most per capita on prescription drugs. Goal: To compare drug spending levels and trends in the U.S. and nine other high-income countries - Australia, Canada, France, Germany, the Netherlands, Norway, Sweden, Switzerland, and the United Kingdom; consider potential explanations for higher U.S. spending; and explore patients' exposure to pharmaceutical costs. Method: Analysis of health data from the Organisation for Economic Co-operation and Development, the 2016 Commonwealth Fund International Health Policy Survey, and other sources. Findings and Conclusions: Various factors contribute to high per capita drug spending in the U.S. While drug utilization appears to be similar in the U.S. and the nine other countries considered, the prices at which drugs are sold in the U.S. are substantially higher. These price differences appear to at least partly explain current and historical disparities in spending on pharmaceutical drugs. U.S. consumers face particularly high out-of-pocket costs, both because the U.S. has a large uninsured population and because cost-sharing requirements for those with coverage are more burdensome than in other countries. Most Americans support reducing pharmaceutical costs. International experience demonstrates that policies like universal health coverage, insurance benefit design that restricts out-of-pocket spending, and certain price control strategies, like centralized price negotiations,can be effective. PMID- 28990748 TI - Cal MediConnect Enrollment: Why Are Dual-Eligible Consumers in Los Angeles County Opting Out? AB - Los Angeles County has the state's lowest rate of consumer enrollment in Cal MediConnect, a program that is responsible for the delivery and coordination of medical, behavioral health, and long-term services and support benefits for individuals who are dually eligible for Medicare and Medi-Cal. This policy brief examines the factors that influence consumer decisions and may contribute to low enrollment rates. Influential factors include consumer knowledge of health care options, perception of choice, and disruption of existing care. Differences in decision making by age, complexity of health care needs, race/ethnicity, immigration status, and primary language are also noted. Policy recommendations include engaging consumers in the planning and dissemination of information about their health care options, optimizing consumer choice and implementing the least disruptive pathway to enrollment, and recognizing and responding to the great diversity of dual-eligible consumers in Los Angeles County. PMID- 28990749 TI - Structurally Simple and Easily Accessible Perylenes for Dye-Sensitized Solar Cells Applicable to Both 1 Sun and Dim-Light Environments. AB - The need for low-cost and highly efficient dyes for dye-sensitized solar cells under both the sunlight and dim light environments is growing. We have devised GJ series push-pull organic dyes which require only four synthesis steps. These dyes feature a linear molecular structure of donor-perylene-ethynylene-arylcarboxylic acid, where donor represents N,N-diarylamino group and arylcarboxylic groups represent benzoic, thienocarboxylic, 2-cyano-3-phenylacrylic, 2-cyano-3 thienoacrylic, and 4-benzo[c][1,2,5]thiadiazol-4-yl-benzoic groups. In this study, we demonstrated that a dye without tedious and time-consuming synthesis efforts can perform efficiently. Under the illumination of AM1.5G simulated sunlight, the benzothiadiazole-benzoic-containing GJ-BP dye shows the best power conversion efficiency (PCE) of 6.16% with VOC of 0.70 V and JSC of 11.88 mA cm-2 using liquid iodide-based electrolyte. It also shows high performance in converting light of 6000 lx light intensity, that is, incident power of ca. 1.75 mW cm-2, to power output of 0.28 mW cm-2 which equals a PCE of 15.79%. Interestingly, the benzoic-containing dye GJ-P with a simple molecular structure has comparable performance in generating power output of 0.26 mW cm-2 (PCE of 15.01%) under the same condition and is potentially viable toward future application. PMID- 28990750 TI - Organic-Inorganic Composite Films Based on Gd3Ga3Al2O12:Ce Scintillator Nanoparticles for X-ray Imaging Applications. AB - Organic-inorganic nanocomposite self-standing films of Gd3Ga3Al2O12 (GGAG) uniformly dispersed in poly(methyl methacrylate) (PMMA) and polystyrene polymer are prepared for radiography application. GGAG:Ce nanoscintillator has been chosen because of its high light output and fast decay time. The nanopowder of GGAG is synthesized by coprecipitation method and dispersed in the polymer matrix by a simple blending technique. The nanocomposite films of thickness in the range of 150-450 MUm with a very high inorganic content is achieved by this technique. These films are characterized by their uniformity, optical absorption, photoluminescence, and radioluminescence. These films are further tested for their application in radiography by recording X-ray images using a commercially available charge-coupled device camera. A resolution of 10 lp/mm is obtained using GGAG:PMMA composite film with 50% loading, confirming their application in imaging devices. PMID- 28990751 TI - MOF-Derived ZnO Nanoparticles Covered by N-Doped Carbon Layers and Hybridized on Carbon Nanotubes for Lithium-Ion Battery Anodes. AB - Metal-organic frameworks (MOFs) have many promising applications in energy and environmental areas such as gas separation, catalysis, supercapacitors, and batteries; the key toward those applications is controlled pyrolysis which can tailor the porous structure, improve electrical conductivity, and expose metal ions in MOFs. Here, we present a systematic study on the structural evolution of zeolitic imidazolate frameworks hybridized on carbon nanotubes (CNTs) during the carbonization process. We show that a number of typical products can be obtained, depending on the annealing time, including (1) CNTs wrapped by relatively thick carbon layers, (2) CNTs grafted by ZnO nanoparticles which are covered by thin nitrogen-doped carbon layers, and (3) CNTs grafted by aggregated ZnO nanoparticles. We also investigated the electrochemical properties of those hybrid structures as freestanding membrane electrodes for lithium ion batteries, and the second one (CNT-supported ZnO covered by N-doped carbon) shows the best performance with a high specific capacity (850 mA h/g at a current density of 100 mA/g) and excellent cycling stability. Our results indicate that tailoring and optimizing the MOF-CNT hybrid structure is essential for developing high performance energy storage systems. PMID- 28990752 TI - Monomer: Design of ZnO Nanostructures (Nanobush and Nanowire) and Their Room Temperature Ethanol Vapor Sensing Signatures. AB - Ethanol serves as a biomarker as well as a chemical reagent for several applications and has been predominantly used as an alternative fuel (E10 and E85). Development of sensors for the detection and monitoring of ethanol vapor at lower operating temperatures has gathered momentum in the recent past. In this work, we reported the synthesis of self-assembled ZnO nanowires using electrospun technique without using any external surfactants or capping agents and their room temperature ethanol sensing properties. An inherent template namely monomer of the polymer poly(vinyl alcohol) (PVA) with two different molecular weights (14 000 and 140 000 g mol-1) was used along with the precursor zinc acetate dihydrate. The ZnO-PVA nanofibers have been tranformed to ZnO nanospheres and nanowires after calcination. The ratio of zinc precursor concentration to PVA polymer led to the enhanced carrier concentration of the resultant ZnO nanowire that enhanced, in turn, the sensing response toward ethanol vapor. The developed sensing elements have been systematically characterized to correlate their structural, morphological, and electrical properties with the respective room temperature ethanol-sensing characteristics. The role of grain features and low activation energy of ZnO nanowires in coordination with the low dipole moment of ethanol resulted in the excellent response of 78 toward 100 ppm at room temperature with ultra-sensitive response and recovery times (9 and 12 s, respectively). PMID- 28990754 TI - Effect of an Interfacial Layer on Electron Tunneling through Atomically Thin Al2O3 Tunnel Barriers. AB - Electron tunneling through high-quality, atomically thin dielectric films can provide a critical enabling technology for future microelectronics, bringing enhanced quantum coherent transport, fast speed, small size, and high energy efficiency. A fundamental challenge is in controlling the interface between the dielectric and device electrodes. An interfacial layer (IL) will contain defects and introduce defects in the dielectric film grown atop, preventing electron tunneling through the formation of shorts. In this work, we present the first systematic investigation of the IL in Al2O3 dielectric films of 1-6 A's in thickness on an Al electrode. We integrated several advanced approaches: molecular dynamics to simulate IL formation, in situ high vacuum sputtering atomic layer deposition (ALD) to synthesize Al2O3 on Al films, and in situ ultrahigh vacuum scanning tunneling spectroscopy to probe the electron tunneling through the Al2O3. The IL had a profound effect on electron tunneling. We observed a reduced tunnel barrier height and soft-type dielectric breakdown which indicate that defects are present in both the IL and in the Al2O3. The IL forms primarily due to exposure of the Al to trace O2 and/or H2O during the pre-ALD heating step of fabrication. As the IL was systematically reduced, by controlling the pre-ALD sample heating, we observed an increase of the ALD Al2O3 barrier height from 0.9 to 1.5 eV along with a transition from soft to hard dielectric breakdown. This work represents a key step toward the realization of high quality, atomically thin dielectrics with electron tunneling for the next generation of microelectronics. PMID- 28990753 TI - Novel Electrophilic Scaffold for Imaging of Essential Penicillin-Binding Proteins in Streptococcus pneumoniae. AB - Peptidoglycan (PG) is a mesh-like heteropolymer made up of glycan chains cross linked by short peptides and is the major scaffold of eubacterial cell walls, determining cell shape, size, and chaining. This structure, which is required for growth and survival, is located outside of the cytoplasmic membrane of bacterial cells, making it highly accessible to antibiotics. Penicillin-binding proteins (PBPs) are essential for construction of PG and perform transglycosylase activities to generate the glycan strands and transpeptidation to cross-link the appended peptides. The beta-lactam antibiotics, which are among the most clinically effective antibiotics for the treatment of bacterial infections, inhibit PBP transpeptidation, ultimately leading to cell lysis. Despite this importance, the discrete functions of individual PBP homologues have been difficult to determine. These major gaps in understanding of PBP activation and macromolecular interactions largely result from a lack of tools to assess the functional state of specific PBPs in bacterial cells. We have identified beta lactones as a privileged scaffold for the generation of PBP-selective probes and utilized these compounds for imaging of the essential proteins, PBP2x and PBP2b, in Streptococcus pneumoniae. We demonstrated that while PBP2b activity is restricted to a ring surrounding the division sites, PBP2x activity is present both at the septal center and at the surrounding ring. These spatially separate regions of PBP2x activity could not be detected by previous activity-based approaches, which highlights a critical strength of our PBP-selective imaging strategy. PMID- 28990755 TI - Tunable and Linker Free Nanogaps in Core-Shell Plasmonic Nanorods for Selective and Quantitative Detection of Circulating Tumor Cells by SERS. AB - Controlling the size, number, and shape of nanogaps in plasmonic nanostructures is of significant importance for the development of novel quantum plasmonic devices and quantitative sensing techniques such as surface-enhanced Raman scattering (SERS). Here, we introduce a new synthetic method based on coordination interactions and galvanic replacement to prepare core-shell plasmonic nanorods with tunable enclosed nanogaps. Decorating Au nanorods with Raman reporters that strongly coordinate Ag+ ions (e.g., 4-mercaptopyridine) afforded uniform nucleation sites to form a sacrificial Ag shell. Galvanic replacement of the Ag shell by HAuCl4 resulted in Au-AgAu core-shell structure with a uniform intra-nanoparticle gap. The size (length and width) and morphology of the core-shell plasmonic nanorods as well as the nanogap size depend on the concentration of the coordination complexes formed between Ag+ ions and 4 mercaptopyridine. Moreover, encapsulating Raman reporters within the nanogaps afforded an internal standard for sensitive and quantitative SERS analysis. To test the applicability, core-shell plasmonic nanorods were functionalized with aptamers specific to circulating tumor cells such as MCF-7 (Michigan Cancer Foundation-7, breast cancer cell line). This system could selectively detect as low as 20 MCF-7 cells in a blood mimicking fluid employing SERS. The linking DNA duplex on core-shell plasmonic nanorods can also intercalate hydrophobic drug molecules such as Doxorubicin, thereby increasing the versatility of this sensing platform to include drug delivery. Our synthetic method offers the possibility of developing multifunctional SERS-active materials with a wide range of applications including biosensing, imaging, and therapy. PMID- 28990756 TI - Development of Sphere-Polymer Brush Hierarchical Nanostructure Substrates for Fabricating Microarrays with High Performance. AB - In this work, a sphere-polymer brush hierarchical nanostructure-modified glass slide has been developed for fabricating high-performance microarrays. The substrate consists of a uniform 160 nm silica particle-self-assembled monolayer on a glass slide with a postcoated poly(glycidyl methacrylate) (PGMA) brush layer (termed PGMA@3D(160) substrate), which can provide three-dimensional (3D) polymer brushes containing abundant epoxy groups for directly immobilizing various biomolecules. As a typical example, the interactions of three monosaccharides (4 aminophenyl beta-d-galactopyranoside, 4-aminophenyl beta-d-glucopyranoside, and 4 aminophenyl alpha-d-mannopyranoside) with two lectins (biotinylated ricinus communis agglutinin 120 and biotinylated concanavalin A from Canavalia ensiformis) have been assessed by PGMA@3D(160) substrate-based carbohydrate microarrays. The carbohydrate microarrays show good selectivity, strong multivalent interaction, and low limit of detection (LOD) in the picomolar range without any signal amplification. Furthermore, the proposed sphere-polymer brush hierarchical nanostructure substrates can be easily extended to fabricate other types of microarrays for DNA and protein detection. PGMA@3D(160) substrate-based microarrays exhibit higher reaction efficiencies and lower LODs (by at least 1 order of magnitude) in comparison to those of two-dimensional microarrays, which are fabricated on planar epoxy substrates, making it a promising platform for bioanalytical and biomedical applications. PMID- 28990757 TI - Preparation of Iridescent 2D Photonic Crystals by Using a Mussel-Inspired Spatial Patterning of ZIF-8 with Potential Applications in Optical Switch and Chemical Sensor. AB - In this work, spatial patterning of a thin, dense, zeolitic imidazolate framework (ZIF-8) pattern was generated using photolithography and nanoscale (60 nm) dopamine coating. A bioinspired, unique, reversible, two-color iridescent pattern can be easily obtained for potential applications in sensing and photonics. PMID- 28990758 TI - Breath-Taking Patterns: Discontinuous Hydrophilic Regions for Photonic Crystal Beads Assembly and Patterns Revisualization. AB - Surfaces patterned with hydrophilic and hydrophobic regions provide robust and versatile means for investigating the wetting behaviors of liquids, surface properties analysis, and producing patterned arrays. However, the fabrication of integral and uniform arrays onto these open systems remains a challenge, thus restricting them from being used in practical applications. Here, we present a simple yet powerful approach for the fabrication of water droplet arrays and the assembly of photonic crystal bead arrays based on hydrophilic-hydrophobic patterned substrates. Various integral arrays are simply prepared in a high quality output with a low cost, large scale, and uniform size control. By simply taking a breath, which brings moisture to the substrate surface, complex hydrophilic-hydrophobic outlined images can be revisualized in the discontinuous hydrophilic regions. Integration of hydrogel photonic crystal bead arrays into the "breath-taking" process results in breath-responsive photonic crystal beads, which can change their colors upon a mild exhalation. This state-of-the-art technology not only provides an effective methodology for the preparation of patterned arrays but also demonstrates intriguing applications in information storage and biochemical sensors. PMID- 28990759 TI - Uniform Gold-Nanoparticle-Decorated {001}-Faceted Anatase TiO2 Nanosheets for Enhanced Solar-Light Photocatalytic Reactions. AB - The {001}-faceted anatase TiO2 micro-/nanocrystals have been widely investigated for enhancing the photocatalysis and photoelectrochemical performance of TiO2 nanostructures, but their practical applications still require improved energy conversion efficiency under solar-light and enhanced cycling stability. In this work, we demonstrate the controlled growth of ultrathin {001}-faceted anatase TiO2 nanosheets on flexible carbon cloth for enhancing the cycling stability, and the solar-light photocatalytic performance of the synthesized TiO2 nanosheets can be significantly improved by decorating with vapor-phase-deposited uniformly distributed plasmonic gold nanoparticles. The fabricated Au-TiO2 hybrid system shows an 8-fold solar-light photocatalysis enhancement factor in photodegrading Rhodamine B, a high photocurrent density of 300 MUA cm-2 under the illumination of AM 1.5G, and 100% recyclability under a consecutive long-term cycling measurement. Combined with electromagnetic simulations and systematic control experiments, it is believed that the tandem-type separation and transition of plasmon-induced hot electrons from Au nanoparticles to the {001} facet of anatase TiO2, and then to the neighboring {101} facet, is responsible for the enhanced solar-light photochemical performance of the hybrid system. The Au-TiO2 nanosheet system addresses well the problems of the limited solar-light response of anatase TiO2 and fast recombination of photogenerated electron-hole pairs, representing a promising high-performance recyclable solar-light-responding system for practical photocatalytic reactions. PMID- 28990760 TI - Transformation of Metal-Organic Frameworks/Coordination Polymers into Functional Nanostructured Materials: Experimental Approaches Based on Mechanistic Insights. AB - Nanostructured materials such as porous metal oxides, metal nanoparticles, porous carbons, and their composites have been intensively studied due to their applications, including energy conversion and storage devices, catalysis, and gas storage. Appropriate precursors and synthetic methods are chosen for synthesizing the target materials. About a decade ago, metal-organic frameworks (MOFs) and coordination polymers (CPs) emerged as new precursors for these nanomaterials because they contain both organic and inorganic species that can play parallel roles as both a template and a precursor under given circumstances. Thermal conversions of MOFs offer a promising toolbox for synthesizing functional nanomaterials that are difficult to obtain using conventional methods. Although understanding the conversion mechanism is important for designing MOF precursors for the synthesis of nanomaterials with desired physicochemical properties, comprehensive discussions revealing the transformation mechanism remain insufficient. This Account reviews the utilization of MOFs/CPs as precursors and their transformation into functional nanomaterials with a special emphasis on understanding the relationship between the intrinsic nature of the parent MOFs and the daughter nanomaterials while discussing various experimental approaches based on mechanistic insights. We discuss nanomaterials categorized by materials such as metal-based nanomaterials and porous carbons. For metal-based nanomaterials transformed from MOFs, the nature of metal ions in the MOF scaffolds affects the physicochemical properties of the resultant materials including the phase, composite, and morphology of nanomaterials. Organic ligands are also involved in the in situ chemical reactions with metal species during thermal conversion. We describe these conversion mechanisms by classifying the phase of metal components in the resultant materials. Along with the metal species, carbon is a major element in MOFs, and thus, the appropriate choice of precursor MOFs and heat treatment can be expected to yield carbon-based nanomaterials. We address the relationship between the nature of the parent MOF and the porosity of the daughter carbon material-a controversial issue in the synthesis of porous carbons. Based on an understanding of the mechanism of MOF conversion, morphologically or compositionally advanced materials are synthesized by adopting appropriate MOF precursors and thermolysis conditions. Despite the progressive understanding of conversion phenomena of MOFs/CPs, this research field still has rooms to be explored and developed, ultimately in order to precisely control the properties of resultant nanomaterials. In this sense, we should pay more attention to the mechanism investigations of MOF conversion. We believe this Account will facilitate a deeper understanding of MOF/CP conversion routes and will accelerate further development in this field. PMID- 28990761 TI - Multimicrometer Noncovalent Monolayer Domains on Layered Materials through Thermally Controlled Langmuir-Schaefer Conversion for Noncovalent 2D Functionalization. AB - As functionalized 2D materials are incorporated into hybrid materials, ensuring large-area structural control in noncovalently adsorbed films becomes increasingly important. Noncovalent functionalization avoids disrupting electronic structure in 2D materials; however, relatively weak molecular interactions in such monolayers typically reduce stability toward solution processing and other common material handling conditions. Here, we find that controlling substrate temperature during Langmuir-Schaefer conversion of a standing phase monolayer of diynoic amphiphiles on water to a horizontally oriented monolayer on a 2D substrate routinely produces multimicrometer domains, at least an order of magnitude larger than those typically achieved through drop casting. Following polymerization, these highly ordered monolayers retain their structures during vigorous washing with solvents including water, ethanol, tetrahydrofuran, and toluene. These findings point to a convenient and broadly applicable strategy for noncovalent functionalization of 2D materials in applications that require large-area structural control, for instance, to minimize desorption at defects during subsequent solution processing. PMID- 28990762 TI - Multichanneled Nerve Guidance Conduit with Spatial Gradients of Neurotrophic Factors and Oriented Nanotopography for Repairing the Peripheral Nervous System. AB - Peripheral nerve injuries, causing sensory and motor impairment, affect a great number of patients annually. It is therefore important to incorporate different strategies to promote nerve healing. Among the treatment options, however, the efficacy of nerve conduits is often compromised by their lack of living cells, insufficient growth factors, and absence of the extracellular matrix (ECM)-like structure. To improve the functional recovery, we aimed to develop a natural biodegradable multichanneled scaffold characterized with aligned electrospun nanofibers and neurotrophic gradient (MC/AN/NG) to guide axon outgrowth. The gelatin-based conduits mimicked the fascicular architecture of natural nerve ECM. The multichanneled (MC) scaffolds, cross-linked with microbial transglutaminase, possessed sustainable mechanical stability. Meanwhile, the release profile of dual neurotrophic factors, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), exhibited a temporal-controlled manner. In vitro, the differentiated neural stem cells effectively extended their neurites along the aligned nanofibers. Besides, in the treated group, the cell density increased in high NGF concentration regions of the gradient membrane, and the BDNF significantly promoted myelination. In a rabbit sciatic nerve transection in vivo model, the MC/AN/NG scaffold showed superior nerve recovery and less muscle atrophy comparable to autograft. By integrating multiple strategies to promote peripheral nerve regeneration, the MC/AN/NG scaffolds as nerve guidance conduits showed promising results and efficacious treatment alternatives for autologous nerve grafts. PMID- 28990763 TI - Significance of a Noble Metal Nanolayer on the UV and Visible Light Photocatalytic Activity of Anatase TiO2 Thin Films Grown from a Scalable PECVD/PVD Approach. AB - UV and visible light photocatalytic composite Pt and Au-TiO2 coatings have been deposited on silicon and glass substrates at low temperature using a hybrid ECWR PECVD/MS-PVD process. Methylene blue, stearic acid, and sulfamethoxazole were used as dye, organic, and antibiotic model pollutants, respectively, to demonstrate the efficiency of these nanocomposite coatings for water decontamination or self-cleaning surfaces applications. Raman investigations revealed the formation of anatase polymorph of TiO2 in all synthesized coatings with a shifting of the main vibrational mode peak to higher wavenumber in the case of Au-TiO2 coating, indicating an increase number of crystalline defects within this coating. Because of the difference of the chemical potentials of each of the investigated noble metals, the sputtered metal layers exhibit different morphology. Pt sputtered atoms, with high surface adhesion, promote formation of a smooth 2D layer. On the other hand, Au sputtered atoms with higher cohesive forces promote the formation of 5-10 nm nanoparticles. As a result, the surface plasmon resonance phenomenon was observed in the Au-TiO2 coatings. UV photoactivity of the nanocomposite coatings was enhanced 1.5-3 times and 1.3 times for methylene blue and stearic acid, respectively, thanks to the enhancement of electron trapping in the noble metal layer. This electron trapping phenomenon is higher in the Pt-TiO2 coating because of its larger work function. On the other hand, the enhancement of the visible photoactivity was more pronounced (3 and 7 times for methylene blue and stearic acid, respectively) in the case of Au-TiO2 thanks to the surface plasmon resonance. Finally, these nanocomposite TiO2 coatings exhibited also a good ability for the degradation of antibiotics usually found in wastewater such as sulfamethoxazole. However, a complementary test have showed an increase of the toxicity of the liquid medium after photocatalysis, which could be due the presence of sulfamethoxazole's transformation byproducts. PMID- 28990764 TI - Slow Magnetic Relaxation in Ladder-Type and Single-Strand 2p-3d-4f Heterotrispin Chains. AB - Ladder-type and chain 2p-3d-4f complexes based on a bridging nitronyl nitroxide radical, namely, [LnCu(hfac)5(NIT-Ph-p-OCH2trz)].0.5C6H14 [Ln = Y (1a), Dy (1b)] and [LnCu(hfac)5(NIT-Ph-p-OCH2trz)] [Ln = Y (2a), Dy (2b); NIT-Ph-p-OCH2trz = 2 [4-[(1H-1,2,4-triazol-1-yl)methoxy]phenyl]-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide; hfac = hexafluoroacetylacetonate) have been successfully achieved through a one-pot reaction of the NIT-Ph-p-OCH2trz radical with Cu(hfac)2 and Ln(hfac)3.2H2O. Complexes 1a and 1b feature a ladder-like structure, where the rails are made of Ln(III) and Cu(II) ions alternatively bridged by nitronyl nitroxide and the triazole units while the NIT-Ph-p-OCH2trz moieties act as the rungs of the ladder. Complexes 2a and 2b consist of one-dimensional nitronyl nitroxide bridged Ln coordination polymers with dangly Cu(II) units connected to the triazole moieties. All of compounds exhibit ferromagnetic NIT-Dy and/or NIT Cu interactions. Both Dy derivatives (1b and 2b) show frequency-dependent out-of phase magnetic susceptibility signals in a zero field indicating slow magnetic relaxation behavior. PMID- 28990766 TI - Efficient Bacterial Inactivation by Transition Metal Catalyzed Auto-Oxidation of Sulfite. AB - Disinfection is an indispensable process in wastewater treatment plants. New bacterial inactivation technologies are of increasing interest and persistent demand. A category of simple and efficient bactericidal systems have been established in this study, that is, the combination of divalent transition metal (Mn(II), Co(II), Fe(II), or Cu(II)) and sulfite. In these systems, metal catalyzed auto-oxidation of sulfite was manifested to generate reactive intermediary SO4*- that played the major role in Escherichia coli inactivation at pH 5-8.5. Increasing concentrations of metal ion or sulfite, and lower pH, led to higher bacterial deaths. Bacterial inactivation by Me(II)/sulfite systems was demonstrated to be a surface-bound oxidative damage process through destructing vital cellular components, such as NADH and proteins. Additionally, the developed Me(II)/sulfite systems also potently killed other microbial pathogens, that is, Pseudomonas aeruginosa, Bacillus subtilis, and Cu(II)-antibiotic-resistant E. coli. The efficacy of Me(II)/sulfite in treating real water samples was further tested with two sewages from a wastewater treatment plant and a natural lake water body, and Cu(II)/sulfite and Co(II)/sulfite rapidly inactivated viable bacteria regardless of bacteria species and cell density, therefore holding great promises for wastewater disinfection. PMID- 28990765 TI - Self-Assembling Ability Determines the Activity of Enzyme-Instructed Self Assembly for Inhibiting Cancer Cells. AB - Enzyme-instructed self-assembly (EISA) represents a dynamic continuum of supramolecular nanostructures that selectively inhibits cancer cells via simultaneously targeting multiple hallmark capabilities of cancer, but how to design the small molecules for EISA from the vast molecular space remains an unanswered question. Here we show that the self-assembling ability of small molecules controls the anticancer activity of EISA. Examining the EISA precursor analogues consisting of an N-capped d-tetrapeptide, a phosphotyrosine residue, and a diester or a diamide group, we find that, regardless of the stereochemistry and the regiochemistry of their tetrapeptidic backbones, the anticancer activities of these precursors largely match their self-assembling abilities. Additional mechanistic studies confirm that the assemblies of the small peptide derivatives result in cell death, accompanying significant rearrangement of cytoskeletal proteins and plasma membranes. These results imply that the diester or diamide derivatives of the d-tetrapeptides self-assemble pericellularly, as well as intracellularly, to result in cell death. As the first case to correlate thermodynamic properties (e.g., self-assembling ability) of small molecules with the efficacy of a molecule process against cancer cells, this work provides an important insight for developing a molecular dynamic continuum for potential cancer therapy, as well as understanding the cytotoxicity of pathogenic assemblies. PMID- 28990767 TI - Three Mixed-Alkaline Borates: Na2M2B20O32 (M = Rb, Cs) with Two Interpenetrating Three-Dimensional B-O Networks and Li4Cs4B40O64 with Fundamental Building Block B40O77. AB - Three new mixed-alkaline borates Na2M2B20O32 (M = Rb, Cs) and Li4Cs4B40O64 with unique structures were synthesized by the spontaneous nucleation method, and their structures were determined by single-crystal X-ray diffraction. The B-O networks of Na2M2B20O32 (M = Rb, Cs) are constructed by two independent interpenetrating three-dimensional (3D) frameworks, which is the first case in anhydrous mixed-alkaline borate systems. In addition, Li4Cs4B40O64 shows high B-O polymerization with a new fundamental building block B40O77. Meanwhile, detailed structure comparisons containing the cation effect on the framework have been discussed. UV-vis-NIR diffuse reflectance spectra and the infrared spectra were measured. The band structures and the density of states were performed using density functional theory calculation. PMID- 28990768 TI - Reactions of Germylenes and Stannylenes with Halo(hydrocarbyl)- and Chloro(amino)phosphines: Oxidative Addition versus Ligand Transfer. AB - Oxidative addition (OA) is an important elementary step in chemistry, but it has been studied mainly in the context of transition-metal-catalyzed reactions and mainly with carbon-X substrates (X = halogen, H). Reports of main-group metal compounds undergoing OA are rare by comparison, and those involving phosphorus halogen substrates are rarer still. Acyclic and cyclic diazagermylenes and stannylenes react with chloro(hydrocarbyl)phosphines with the intermediacy of oxidative addition products. Stannylenes react faster than germylenes, and these reactions are first-order in both reactants and slowed by steric bulk. Kinetic data and the structures of intermediates and products had suggested an adduct/insertion mechanism for these reactions. To gain further insight into these transformations, the work presented herein was extended to chloro(hydrocarbyl)phosphines with varying organic substituents. These studies confirmed prior conclusions concerning the rate-diminishing effect of steric bulk, and the rate dependence on leaving groups also seems to suggest adduct/insertion or SN2 mechanisms. Importantly, these new data now also point to associative decomposition pathways. In the course of the investigation, it was discovered that aliphatic chloro(amino)phosphines react differently with the carbene analogues, giving oxidative addition products for germylenes but metathesis reactions for stannylenes. PMID- 28990769 TI - Rapid and Concomitant Analysis of Pharmaceuticals in Treated Wastewater by Coated Blade Spray Mass Spectrometry. AB - The widespread use of pharmaceuticals in both human and animal populations, and the resultant contamination of surface waters from the outflow of water treatment facilities is an issue of growing concern. This has raised the need for analytical methods that can both perform rapid sample analysis and overcome the limitations of conventional analysis procedures, such as multistep workflows and tedious procedures. Coated blade spray (CBS) is a solid-phase microextraction based technique that enables the direct-to-mass-spectrometry analysis of extracted compounds via the use of limited organic solvent to desorb analytes and perform electrospray ionization. This paper documents how CBS can be applied for the concomitant tandem mass spectrometric (MS/MS) analysis of nine pharmaceuticals in treated wastewater. The total analysis times of less than 11 min provided limits of detection lower than 50 ng L-1 for all target compounds in river water. The CBS methodology was then compared to a conventional solid-phase extraction technique for the analysis of the final effluent of six wastewater treatment facilities. The experimental results strongly suggest that CBS offers scientists a viable alternative method for analyzing water samples that is both rapid and relatively solvent-free. PMID- 28990770 TI - Design, Synthesis, and Potency of Pyruvate Dehydrogenase Complex E1 Inhibitors against Cyanobacteria. AB - Safe and effective algaecides are needed to control agriculturally and environmentally significant algal species. Four series (6, 10, 17, and 21) of 29 novel 4-aminopyrimidine derivatives were rationally designed and synthesized. A part of 10, 17, and 21 displayed potent inhibition of Escherichia coli pyruvate dehydrogenase complex E1 (E. coli PDHc-E1) (IC50 = 2.12-18.06 MUM) and good inhibition of Synechocystis sp. PCC 6803 (EC50 = 0.7-7.1 MUM) and Microcystis sp. FACH 905 (EC50 = 3.7-7.6 MUM). The algaecidal activity of these compounds positively correlated with their inhibition of E. coli PDHc-E1. In particular, 21l and 10b exhibited potent algaecidal activity against PCC 6803 (EC50 = 0.7 and 0.8 MUM, respectively), values that were 2-fold increased compared to that of copper sulfate (EC50 = 1.8 MUM), and showed the best inhibition of cyanobacterium PDHc-E1 (IC50 = 5.10 and 6.06 MUM, respectively). 17h and 21e, the best inhibitors of E. coli PDHc-E1, were studied by molecular docking, site-directed mutagenesis, and enzymatic assays. These results revealed that the improved inhibition of novel inhibitors compared with that of the lead compound I was due to the formation of a new hydrogen bond with Leu264 at the active site of E. coli PDHc-E1. The results proved the great potential to obtain effective algaecides via the rational design of PDHc-E1 inhibitors. PMID- 28990771 TI - Antibiotic Resistance Genes and Associated Microbial Community Conditions in Aging Landfill Systems. AB - Landfills receive about 350 million tons of municipal solid wastes (MSWs) per year globally, including antibiotics and other coselecting agents that impact antimicrobial resistance (AMR). However, little is known about AMR in landfills, especially as a function of landfill ages. Here we quantified antibiotics, heavy metals, and AMR genes (ARGs) in refuse and leachates from landfills of different age (<3, 10, and >20 years). Antibiotics levels were consistently lower in refuse and leachates from older landfills, whereas ARG levels in leachates significantly increased with landfill age (One-way ANOVA, F = 10.8, P < 0.01). Heavy metals whose contents increased as landfills age (one-way ANOVA, F = 12.3, P < 0.01) were significantly correlated with elevated levels of ARGs (Mantel test, R = 0.66, P < 0.01) in leachates, which implies greater AMR exposure risks around older landfills. To further explain ARGs distributional mechanisms with age, microbial communities, mobile genetic elements (MGEs) and environmental factors were contrasted between refuse and leachate samples. Microbial communities in the refuse were closely correlated with ARG contents (Procrustes test; M2 = 0.37, R = 0.86, P < 0.001), whereas ARG in leachates were more associated with MGEs. PMID- 28990772 TI - Anthropogenic 236U in the North Sea - A Closer Look into a Source Region. AB - In this study we present new seawater data of 236U and 238U sampled in the North Sea in 2010. The North Sea has been and is still receiving a considerable input of anthropogenic radionuclides from nuclear reprocessing facilities located in La Hague (France) and Sellafield (Great Britain). It therefore represents an important source region for oceanographic tracer studies using the transient signal of anthropogenic 236U. A proper knowledge of the sources of 236U is an essential prerequisite for such tracer studies. The 236U data set presented in this study covers the transition regions of the North Sea to the Atlantic Ocean, to the Baltic Sea, and upstream the Elbe River. It is discussed in the context of available 236U data from the literature. Our results show that both 236U concentrations and 236U/238U ratios in surface waters of the North Sea can be explained by simple binary mixing models implying that 236U behaves conservatively in seawater. We further show that the input of 236U by the Elbe River is negligible, while there might be a maximum input of 12 g/yr via the Baltic Sea. The results of the mixing models suggest that this still unidentified 236U contamination could be supplied by fresh water input. PMID- 28990773 TI - N-Heterocyclic Carbene Initiated Anionic Polymerization of (E,E)-Methyl Sorbate and Subsequent Ring-Closing to Cyclic Poly(alkyl sorbate). AB - A diene-based cyclic polymer has been synthesized by the anionic polymerization of methyl sorbate (MS) by an N-heterocyclic carbene (NHC) in the presence of a bulky aluminum Lewis acid. We first polymerized methyl sorbate (MS) initiated by NHC in N,N-dimethylformamide (DMF) at 25 degrees C, poly(MS) with a number average molecular weight (Mn) of 3.5 * 103 (Mw/Mn = 2.1) was obtained with a conversion of 93%. The structure was confirmed by 1H and 13C NMR and IR spectra, which revealed that the propagation proceeded via 1,2-addition as well as 1,4 addition. Although the polymerization did not occur in toluene in the absence of any additive, quantitative monomer consumption was observed in the presence of methylaluminum bis(2,6-di-tert-butyl-4-methylphenoxide) (MAD) to afford the poly(MS) with a 1,4-trans structure, 86% of threo diastereoselectivity, and a Mn of 23.0 * 103 with narrow molecular weight distribution (Mw/Mn = 1.17). From the matrix assisted laser desorption/ionization (MALDI-TOF) mass spectra of poly(MS) and the hydrogenated analogue, ring-closing occurred by nucleophilic attack of the anionic propagating center into the adjacent carbon of the alpha-terminal imidazolimium group to afford cyclic poly(MS). The cyclic formation in the present synthesis system was confirmed by DSC and viscosity measurements. PMID- 28990774 TI - Layered Crystal Structure, Color-Tunable Photoluminescence, and Excellent Thermal Stability of MgIn2P4O14 Phosphate-Based Phosphors. AB - Single-component white phosphors stand a good chance to serve in the next generation high-power white light-emitting diodes. Because of low thermal stability and containing lanthanide ions with reduced valence state, most of reported phosphors usually suffer unstable color of lighting for practical packaging and comparably complex synthetic processes. In this work, we present a type of novel color-tunable blue-white-yellow-emitting MgIn2P4O14:Tm3+/Dy3+ phosphor with high thermal stability, which can be easily fabricated in air. Under UV excitation, the MgIn2P4O14:Tm0.02Dy0.03 white phosphor exhibits negligible thermal-quenching behavior, with a 99.5% intensity retention at 150 degrees C, relative to its initial value at room temperature. The phosphor host MgIn2P4O14 was synthesized and reported for the first time. MgIn2P4O14 crystallizes in the space group of C2/c (No. 15) with a novel layered structure built of alternate anionic and cationic layers. Its disordering structure, with Mg and In atoms co-occupying the same site, is believed to facilitate the energy transfer between rare-earth ions and benefit by sustaining the luminescence with increasing temperature. The measured absolute quantum yields of MgIn2P4O14:Dy0.04, MgIn2P4O14:Tm0.01Dy0.04, and MgIn2P4O14:Tm0.02Dy0.03 phosphors under the excitation of 351 nm ultraviolet radiation are 70.50%, 53.24%, and 52.31%, respectively. Present work indicates that the novel layered MgIn2P4O14 is a promising candidate as a single-component white phosphor host with an excellent thermal stability for near-UV-excited white-light-emitting diodes (wLEDs). PMID- 28990775 TI - Reversible Single-Crystal-to-Single-Crystal Transformation in Photomagnetic Cyanido-Bridged Cd4M2 Octahedral Molecules. AB - Two new hexanuclear octahedral cyanido-bridged clusters, {[CdII(bpy)2]4[WIV(CN)8]2}.10H2O (Cd4W2) and {[CdII(bpy)2]4[MoIV(CN)8]2}.10H2O (Cd4Mo2), have been obtained and characterized structurally and photomagnetically. Both compounds show a very rare and reversible single-crystal to-single-crystal transformation upon dehydration accompanied by marked color changes in the case of Cd4W2. Moreover, irradiation of Cd4Mo2 using 436 nm light induces a reversible photomagnetic effect due to the LIESST-like singlet-triplet transition at the MoIV center. Analogous photomagnetic experiments for Cd4W2 did not lead to any significant change of its magnetic moment. PMID- 28990776 TI - Discovery and Engineering of Pathways for Production of alpha-Branched Organic Acids. AB - Cell-based synthesis offers many opportunities for preparing small molecules from simple renewable carbon sources by telescoping multiple reactions into a single fermentation step. One challenge in this area is the development of enzymatic carbon-carbon bond forming cycles that enable a modular disconnection of a target structure into cellular building blocks. In this regard, synthetic pathways based on thiolase enzymes to catalyze the initial carbon-carbon bond forming step between acyl coenzyme A (CoA) substrates offer a versatile route for biological synthesis, but the substrate diversity of such pathways is currently limited. In this report, we describe the identification and biochemical characterization of a thiolase-ketoreductase pair involved in production of branched acids in the roundworm, Ascaris suum, that demonstrates selectivity for forming products with an alpha-methyl branch using a propionyl-CoA extender unit. Engineering synthetic pathways for production of alpha-methyl acids in Escherichia coli using these enzymes allows the construction of microbial strains that produce either chiral 2 methyl-3-hydroxy acids (1.1 +/- 0.2 g L-1) or branched enoic acids (1.12 +/- 0.06 g L-1) in the presence of a dehydratase at 44% and 87% yield of fed propionate, respectively. In vitro characterization along with in vivo analysis indicates that the ketoreductase is the key driver for selectivity, forming predominantly alpha-branched products even when paired with a thiolase that highly prefers unbranched linear products. Our results expand the utility of thiolase-based pathways and provide biosynthetic access to alpha-branched compounds as precursors for polymers and other chemicals. PMID- 28990777 TI - Ultrahigh Mass Activity for Carbon Dioxide Reduction Enabled by Gold-Iron Core Shell Nanoparticles. AB - Wide application of carbon dioxide (CO2) electrochemical energy storage requires catalysts with high mass activity. Alloy catalysts can achieve superior performance to single metals while reducing the cost by finely tuning the composition and morphology. We used in silico quantum mechanics rapid screening to identify Au-Fe as a candidate improving CO2 reduction and then synthesized and tested it experimentally. The synthesized Au-Fe alloy catalyst evolves quickly into a stable Au-Fe core-shell nanoparticle (AuFe-CSNP) after leaching out surface Fe. This AuFe-CSNP exhibits exclusive CO selectivity, long-term stability, nearly a 100-fold increase in mass activity toward CO2 reduction compared with Au NP, and 0.2 V lower in overpotential. Calculations show that surface defects due to Fe leaching contribute significantly to decrease the overpotential. PMID- 28990778 TI - Benzo[a]pyrene Induces Autophagic and Pyroptotic Death Simultaneously in HL-7702 Human Normal Liver Cells. AB - As a common polycyclic aromatic hydrocarbon compound, benzo[a]pyrene (BaP) is readily produced in processing of oil and fatty foods. It is not only a strong carcinogen but also a substance with strong immunotoxicity and reproduction toxicity. Autophagy and pyroptosis are two types of programmed cell death. Whether or not BaP damages body tissues via autophagy or pyroptosis remains unknown. The present study investigated the effects of BaP on autophagy and pyroptosis in HL-7702 cells. The results showed that BaP induced cell death in HL 7702 cells enhanced the intracellular levels of ROS and arrested the cell cycle at the S phase. Additionally, BaP resulted in cell death through autophagy and pyroptosis. Compared with the BaP group, the autophagy inhibitor 3-MA significantly (p < 0.01) inhibited the release of LDH by 70.53% +/- 0.46 and NO by 50.36% +/- 0.80, the increase of electrical conductivity by 12.08% +/- 0.55, and the expressions of pyroptotic marker proteins (Caspase-1, Cox-2, IL-1beta, IL 18). The pyroptosis inhibitor Ac-YVAD-CM also notably (p < 0.01) blocked BaP induced autophagic cell death characterized by the increase of autophagic vacuoles and overexpression of Beclin-1 and LC3-II. In conclusion, BaP led to injury by inducing autophagy and pyroptosis simultaneously, the two of which coexisted and promoted each other in HL-7702 cells. PMID- 28990780 TI - Lorneic Acid Analogues from an Endophytic Actinomycete. AB - Our natural products discovery program utilizes endophytic actinomycetes associated with plants and employs biological assays and HPLC-based metabolite profiles as the preliminary screen to identify strains of interest, followed by large-scale fermentation and isolation, leading to new and/or bioactive natural products. Six new trialkyl-substituted aromatic acids, namely, lorneic acids E-J (1-6), together with two known analogues (7 and 8), were isolated and identified from the culture extract of Streptomyces sp. KIB-H1289, an endophytic actinomycete obtained from the inner tissue of the bark of Betula mandshurica Nakai. The structures were characterized by interpretation of their spectroscopic data, mainly 1D and 2D NMR. Among them, compound 5 contains a unique disulfide bond that is presumably derived from N-acetylcysteine. All isolated metabolites were evaluated for their inhibitory activity on tyrosinase. PMID- 28990781 TI - Selective Distance Measurements Using Triple Spin Labeling with Gd3+, Mn2+, and a Nitroxide. AB - Distance measurements by pulse electron paramagnetic resonance techniques, such as double electron-electron resonance (DEER, also called PELDOR), have become an established tool to explore structural properties of biomacromolecules and their assemblies. In such measurements a pair of spin labels provides a single distance constraint. Here we show that by employing three different types of spin labels that differ in their spectroscopic and spin dynamics properties it is possible to extract three independent distances from a single sample. We demonstrate this using the Antennapedia homeodomain orthogonally labeled with Gd3+ and Mn2+ tags in complex with its cognate DNA binding site labeled with a nitroxide. PMID- 28990779 TI - Designer alpha1,6-Fucosidase Mutants Enable Direct Core Fucosylation of Intact N Glycopeptides and N-Glycoproteins. AB - Core fucosylation of N-glycoproteins plays a crucial role in modulating the biological functions of glycoproteins. Yet, the synthesis of structurally well defined, core-fucosylated glycoproteins remains a challenging task due to the complexity in multistep chemical synthesis or the inability of the biosynthetic alpha1,6-fucosyltransferase (FUT8) to directly fucosylate full-size mature N glycans in a chemoenzymatic approach. We report in this paper the design and generation of potential alpha1,6-fucosynthase and fucoligase for direct core fucosylation of intact N-glycoproteins. We found that mutation at the nucleophilic residue (D200) did not provide a typical glycosynthase from this bacterial enzyme, but several mutants with mutation at the general acid/base residue E274 of the Lactobacillus casei alpha1,6-fucosidase, including E274A, E274S, and E274G, acted as efficient glycoligases that could fucosylate a wide variety of complex N-glycopeptides and intact glycoproteins by using alpha fucosyl fluoride as a simple donor substrate. Studies on the substrate specificity revealed that the alpha1,6-fucosidase mutants could introduce an alpha1,6-fucose moiety specifically at the Asn-linked GlcNAc moiety not only to GlcNAc-peptide but also to high-mannose and complex-type N-glycans in the context of N-glycopeptides, N-glycoproteins, and intact antibodies. This discovery opens a new avenue to a wide variety of homogeneous, core-fucosylated N-glycopeptides and N-glycoproteins that are hitherto difficult to obtain for structural and functional studies. PMID- 28990782 TI - Synthesis of Functionalized Pyridines via Cu(II)-Catalyzed One-Pot Cascade Reactions of Inactivated Saturated Ketones with Electron-Deficient Enamines. AB - In this paper, a novel and efficient synthesis of 3-acylpyridines and pyridine-3 carboxylates through the oxidative one-pot sequential reactions of inactivated saturated ketones with electron-deficient enamines is presented. Mechanistically, the formation of the title compounds involves the in situ formation of an enone intermediate through an oxidative dehydrogenation of the saturated ketone substrate, followed by its [3+3] annulation with beta-enaminone or beta enaminoester via a cascade process, including Michael addition, aldol type condensation, and oxidative aromatization. PMID- 28990783 TI - Quantification of Total Vitamin-D-Binding Protein and the Glycosylated Isoforms by Liquid Chromatography-Isotope Dilution Mass Spectrometry. AB - Vitamin-D-binding protein (VDBP), a transporter of 25-hydroxyvitamin D metabolites, has three common isoforms. The relationship of the isoforms and their glycosylation state with various diseases has been under recent examination. In this work, liquid chromatography coupled to isotope dilution mass spectrometry was evaluated for quantification of VDBP, the three common isoforms, and total glycosylation. Protocols using guanidine, urea, RapiGest, trifluoroethanol, or tris buffer were also evaluated for optimal tryptic digestion. Differences in peptide release were detected between purified and plasma VDBP; however, for both protein sources, ELPEHTVK, TSALSAK, and VLEPTLK concentrations were reproducible between most protocols tested. The isoform specific peptides, LPDATPK, LPDATPTELAK, and LPEATPTELAK, were optimally released when TFE was added to plasma. The total VDBP concentration calculated from the three shared peptides resulted in 97.6% accuracy compared with the concentration from amino acid analysis. Glycosylation of VDBP was also calculated for purified protein and donor samples using the ratio of the isoform-specific peptide(s) to the total protein concentration. Glycosylation of purified VDBP was found to be 99.5-111.1% the value determined by semiquantitative analysis of the intact protein by LC-MS. This approach may be used to quantify other samples containing a mixture of isoforms and post-translational modifications. PMID- 28990784 TI - Cooperative Hydrogen-Bond Dynamics at a Zwitterionic Lipid/Water Interface Revealed by 2D HD-VSFG Spectroscopy. AB - Molecular-level elucidation of hydration at biological membrane interfaces is of great importance for understanding biological processes. We studied ultrafast hydrogen-bond dynamics at a zwitterionic phosphatidylcholine/water interface by two-dimensional heterodyne-detected vibrational sum frequency generation (2D HD VSFG) spectroscopy. The obtained 2D spectra confirm that the anionic phosphate and cationic choline sites are individually hydrated at the interface. Furthermore, the data show that the dynamics of water at the zwitterionic lipid interface is not a simple sum of the dynamics of the water species that hydrate to the separate phosphate and choline. The center line slope (CLS) analysis of the 2D spectra reveals that ultrafast hydrogen-bond fluctuation is not significantly suppressed around the phosphate at the zwitterionic lipid interface, which makes the hydrogen-bond dynamics look similar to that of the bulk water. The present study indicates that the hydrogen-bond dynamics at membrane interfaces is not determined only by the hydrogen bond to a specific site of the interface but is largely dependent on the water dynamics in the vicinity and other nearby moieties, through the hydrogen-bond network. PMID- 28990785 TI - Negative and Positive Confinement Effects in Chiral Separation Chromatography Monitored with Molecular-Scale Precision by In-Situ Electron Paramagnetic Resonance Techniques. AB - Separation of compounds using liquid chromatography is a process of enormous technological importance. This is true in particular for chiral substances, when one enantiomer has the desired set of properties and the other one may be harmful. The degree of development in liquid chromatography is extremely high, but still there is a lack in understanding based on experimental data how selectivity works on a molecular level directly at the surfaces of a porous host material. We have prepared amino-acid containing organosilica as such host materials. Watching the rotational dynamics of chiral spin probes using electron paramagnetic resonance spectroscopy allows us to differentiate between surface adsorbed and free guest species. Diastereotopic selectivity factors were determined, and the influence of chiral surface group density, chemical character of the surface groups, pore-size, and temperature was investigated. We found higher selectivity values in macroporous solids with a rather rigid organosilica network and at lower temperature, indicating the significant effect of confinement effects. In mesoporous materials features are opposed with regards to the T-dependent behavior. From EPR imaging techniques and the resulting (macroscopic) diffusion coefficients, we could confirm that the correlations found on the microscopic level transform also to the macroscopic behavior. Thus, our study is of value for the development of future chromatography materials by design. PMID- 28990787 TI - Real-Space Observation of Nonvolatile Zero-Field Biskyrmion Lattice Generation in MnNiGa Magnet. AB - Magnetic skyrmions, particular those without the support of external magnetic fields over a wide temperature region, are promising as alternative spintronic units to overcome the fundamental size limitation of conventional magnetic bits. In this study, we use in situ Lorentz microscope to directly demonstrate the generation and sustainability of robust biskyrmion lattice at zero magnetic field over a wide temperature range of 16-338 K in MnNiGa alloy. This procedure includes a simple field-cooling manipulation from 360 K (higher than Curie temperature TC ~ 350 K), where topological transition easily occurs by adapting the short-range magnetic clusters under a certain magnetic field. The biskyrmion phase is favored upon cooling below TC. Once they are generated, the robust high density biskyrmions persist even after removing the external magnetic field due to the topological protection and the increased energy barrier. PMID- 28990786 TI - Longitudinal Monitoring of Antibody Responses against Tumor Cells Using Magneto nanosensors with a Nanoliter of Blood. AB - Each immunoglobulin isotype has unique immune effector functions. The contribution of these functions in the elimination of pathogens and tumors can be determined by monitoring quantitative temporal changes in isotype levels. Here, we developed a novel technique using magneto-nanosensors based on the effect of giant magnetoresistance (GMR) for longitudinal monitoring of total and antigen specific isotype levels with high precision, using as little as 1 nL of serum. Combining in vitro serologic measurements with in vivo imaging techniques, we investigated the role of the antibody response in the regression of firefly luciferase (FL)-labeled lymphoma cells in spleen, kidney, and lymph nodes in a syngeneic Burkitt's lymphoma mouse model. Regression status was determined by whole body bioluminescent imaging (BLI). The magneto-nanosensors revealed that anti-FL IgG2a and total IgG2a were elevated and sustained in regression mice compared to non-regression mice (p < 0.05). This platform shows promise for monitoring immunotherapy, vaccination, and autoimmunity. PMID- 28990788 TI - Chromophore-Dependent Intramolecular Exciton-Vibrational Coupling in the FMO Complex: Quantification and Importance for Exciton Dynamics. AB - In this paper, we adopt an approach suitable for monitoring the time evolution of the intramolecular contribution to the spectral density of a set of identical chromophores embedded in their respective environments. We apply the proposed method to the Fenna-Matthews-Olson (FMO) complex, with the objective to quantify the differences among site-dependent spectral densities and the impact of such differences on the exciton dynamics of the system. Our approach takes advantage of the vertical gradient approximation to reduce the computational demands of the normal modes analysis. We show that the region of the spectral density that is believed to strongly influence the exciton dynamics changes significantly in the timescale of tens of nanoseconds. We then studied the impact of the intramolecular vibrations on the exciton dynamics by considering a model of FMO in a vibronic basis and neglecting the interaction with the environment to isolate the role of the intramolecular exciton-vibration coupling. In agreement with the assumptions in the literature, we demonstrate that high frequency modes at energy much larger than the excitonic energy splitting have negligible influence on exciton dynamics despite the large exciton-vibration coupling. We also find that the impact of including the site-dependent spectral densities on exciton dynamics is not very significant, indicating that it may be acceptable to apply the same spectral density on all sites. However, care needs to be taken for the description of the exciton-vibrational coupling in the low frequency part of intramolecular modes because exciton dynamics is more susceptible to low frequency modes despite their small Huang-Rhys factors. PMID- 28990790 TI - Synthesis and Characterization of a Binuclear Copper(II) Naphthoisoamethyrin Complex Displaying Weak Antiferromagnetic Coupling. AB - The reaction between a naphthylbipyrrole-containing hexaphyrin-type expanded porphyrin and copper acetate affords a bench-stable dicopper(II) complex. UV-vis spectroscopy, cyclic voltammetry, and X-ray crystallographic analysis measurements provide support for the conclusion that this complex displays aromatic features. A weak antiferromagnetic exchange interaction between the binuclear copper(II) ions is evidenced by variable-temperature electron paramagnetic resonance and by fitting of the bulk magnetic susceptibility to a dimer model, yielding J = -5.1 cm-1. PMID- 28990789 TI - Singlet Oxygen Production and Biological Activity of Hexanuclear Chalcocyanide Rhenium Cluster Complexes [{Re6Q8}(CN)6]4- (Q = S, Se, Te). AB - Octahedral rhenium cluster complexes have recently emerged as relevant building blocks for the design of singlet oxygen photosensitizing materials toward biological applications such as blue-light photodynamic therapy. However, their singlet oxygen generation ability as well as biological properties have been studied only superficially. Herein we investigate in detail the singlet oxygen photogeneration, dark and photoinduced cytotoxicity, cellular uptake kinetics, cellular localization and in vitro photoinduced oxidative stress, and photodynamic cytotoxicity of the series of octahedral rhenium cluster complexes [{Re6Q8}(CN)6]4-, where Q = S, Se, Te. Our results demonstrate that the selenium containing complex possesses optimal properties in terms of absorption and singlet oxygen productivity. These features coupled with the cellular internalization and low dark toxicity lead to the first photoinduced cytotoxic effect observed for a molecular [{M6Q8}L6] complex, making it a promising object for further study in terms of blue-light PDT. PMID- 28990791 TI - Difference FTIR Studies of Substrate Distribution in Triosephosphate Isomerase. AB - Triosephosphate isomerase (TIM) catalyzes the interconversion between dihydroxyacetone phosphate (DHAP) and d-glyceraldehyde 3-phosphate (GAP), via an enediol(ate) intermediate. Determination of substrate population distribution in the TIM/substrate reaction mixture at equilibrium and characterization of the substrate-enzyme interactions in the Michaelis complex are ongoing efforts toward the understanding of the TIM reaction mechanism. By using isotope-edited difference Fourier transform infrared studies with unlabeled and 13C-labeled substrates at specific carbon(s), we are able to show that in the reaction mixture at equilibrium the keto DHAP is the dominant species and the populations of aldehyde GAP and enediol(ate) are very low, consistent with the results from previous X-ray structural and 13C NMR studies. Furthermore, within the DHAP side of the Michaelis complex, there is a set of conformational substates that can be characterized by the different C2?O stretch frequencies. The C2?O frequency differences reflect the different degree of the C2?O bond polarization due to hydrogen bonding from active site residues. The C2?O bond polarization has been considered as an important component for substrate activation within the Michaelis complex. We have found that in the enzyme-substrate reaction mixture with TIM from different organisms the number of substates and their population distribution within the DHAP side of the Michaelis complex may be different. These discoveries provide a rare opportunity to probe the interconversion dynamics of these DHAP substates and form the bases for the future studies to determine if the TIM-catalyzed reaction follows a simple linear reaction pathway, as previously believed, or follows parallel reaction pathways, as suggested in another enzyme system that also shows a set of substates in the Michaelis complex. PMID- 28990792 TI - Enantioselective Rhodium-Catalyzed Alkenylation of Aliphatic Imines. AB - An efficient, enantioselective rhodium-catalyzed addition of potassium alkenyltrifluoroborates to N-nosyl aliphatic imines has been realized. Good reaction yields and excellent enantioselectivities (94-99% ee) were obtained for a variety of aliphatic imines and nucleophilic alkenyltrifluoroborates. An active rhodium-diene catalyst and the precise reaction condition control proved to be pivotal for success. PMID- 28990793 TI - Leiomyosarcoma of the infratemporal fossa with perineurial spread along the right mandibular nerve: a case report. AB - Leiomyosarcomas are malignant tumors displaying strong smooth muscle differentiation. They can often develop within the GI tract and myometrium, but are particularly rare in the head and neck. Perineurial spread of head and neck cancer is observed in patients with neoplasms of the skin (squamous cell carcinoma, melanoma) or skin appendages (adenoid cystic carcinoma). We report the case of a woman who presented with diplopia and headaches. MRI showed an infratemporal mass lesion and faint enhancement tracking along the mandibular nerve into the wall of the right cavernous sinus. A nerve biopsy revealed leiomyosarcoma. We review the medical literature to provide further insight into the diagnosis and management of this tumor and its peculiar pattern of spread. A similar case was unidentifiable in the literature. PMID- 28990794 TI - Value of the revised Atlanta classification (RAC) and determinant-based classification (DBC) systems in the evaluation of acute pancreatitis. AB - OBJECTIVE: Since increasing acute pancreatitis (AP) severity is significantly associated with mortality, accurate and rapid determination of severity is crucial for effective clinical management. This study investigated the value of the revised Atlanta classification (RAC) and the determinant-based classification (DBC) systems in stratifying severity of acute pancreatitis. METHODS: This retrospective observational cohort study included 480 AP patients. Patient demographics and clinical characteristics were recorded. The primary outcome was mortality, and secondary outcomes were admission to intensive care unit (ICU), duration of ICU stay, and duration of hospital stay. RESULTS: Based on the RAC classification, there were 295 patients with mild AP (MAP), 146 patients with moderate-to-severe AP (MSAP), and 39 patients with severe AP (SAP). Based on the DBC classification, there were 389 patients with MAP, 41 patients with MSAP, 32 patients with SAP, and 18 patients with critical AP (CAP). ROC curve analysis showed that the DBC system had a significantly higher accuracy at predicting organ failure compared to the RAC system (p < .001). Multivariate regression analysis showed that age and ICU stay were independent risk factors of mortality. CONCLUSION: The DBC system had a higher accuracy at predicting organ failure. Age and ICU stay were significantly associated with risk of death in AP patients. A classification of CAP by the DBC system should warrant close attention, and rapid implementation of effective measures to reduce mortality. PMID- 28990797 TI - Competing agendas and other tensions in developing patient-centred communication in audiology education: a qualitative study of educator perspectives. AB - OBJECTIVE: Patient-centred communication (PCC) is an essential skill for effective healthcare provision and is accepted as a core competency in medicine and allied health. In audiology, recent studies have shown that audiologists rarely display PCC in adult hearing interactions. This highlights a need to investigate how PCC is taught and learnt in audiology. There is a paucity of studies on PCC in audiology education. The aim of this study is to examine educator perceptions of teaching PCC, including barriers and facilitators, in Australian graduate audiology programmes. DESIGN: Semi-structured interviews were conducted with audiology educators responsible for communication training. Interview transcripts were analysed using qualitative content analysis. STUDY SAMPLE: Nine participants, including programme coordinators and key teaching staff from all six Australian audiology programmes participated in the study. RESULTS: PCC education was found to be influenced by four emerging themes: professional culture and values, contextual factors, knowledge and understanding of PCC and individual factors. CONCLUSIONS: These results provide an insight into the competing agendas involved in implementing PCC education in both the university and clinical component of audiology programmes. The findings can play a role in refining and building the evidence-base for teaching and facilitating patient-centred audiological care in future audiologists. PMID- 28990796 TI - Homocysteine levels associate with subtle changes in leukocyte DNA methylation: an epigenome-wide analysis. AB - AIM: Homocysteine (Hcy) is a sensitive marker of one-carbon metabolism. Higher Hcy levels have been associated with global DNA hypomethylation. We investigated the association between plasma Hcy and epigenome-wide DNA methylation in leukocytes. METHODS: Methylation was measured using Illumina 450 k arrays in 2035 individuals from six cohorts. Hcy-associated differentially methylated positions and regions were identified using meta-analysis. RESULTS: Three differentially methylated positions cg21607669 (SLC27A1), cg26382848 (AJUBA) and cg10701000 (KCNMA1) at chromosome 19, 14 and 10, respectively, were significantly associated with Hcy. In addition, we identified 68 Hcy-associated differentially methylated regions, the most significant of which was a 1.8-kb spanning domain (TNXB/ATF6B) at chromosome 6. CONCLUSION: We identified novel epigenetic loci associated with Hcy levels, of which specific role needs to be further validated. PMID- 28990798 TI - A new highly oxygenated pregnane and two new 5-hydroxymethylfurfural derivatives from the water decoction of Poria cocos. AB - A new highly oxygenated pregnane steroid, pregn-7-ene-2beta,3alpha,15alpha,20 tetrol (1) and two new 5-hydroxymethylfurfural derivatives, (5-formylfuran-2 yl)methyl 2-hydroxypropanoate (2) and (5-formylfuran-2-yl)methyl 2-(4 hydroxyphenyl)acetate (3), together with four known compounds, were isolated from the water decoction of Poria cocos. Their structures were established on the basis of extensive spectroscopic analysis. Compound 1 showed moderate inhibitory activity and a known compound (3S,6S)-3-[(1R)-1-hydroxyethyl]-6-(phenylmethyl) 2,5-piperazinedione (5) showed weak inhibitory activity against alpha glucosidase, respectively. PMID- 28990799 TI - The effect of dietary energy:protein ratio, protein quality and food allocation on the efficiency of utilisation of protein by broiler chickens. AB - 1. Various theories have been proposed to explain the reduced performance of broilers when given feeds excessively high in protein, but a satisfactory solution to this problem had, up to now, not been found. Three experiments were conducted to test the hypothesis that the efficiency of utilisation of protein (ep) is a linear-plateau function of the ratio between the feed apparent metabolisable energy and digestible crude protein contents (AMEn:DCP) and that dietary protein quality, feed allocation and sex do not influence this relationship. 2. A 'linear-plateau' model successfully described the efficiency of protein utilisation (ep) as a function of AMEn:DCP in all three experiments. In Experiment 1, with both sexes being both ad libitum and control fed, the breakpoint was at 58.6 MJ AMEn/kg DCP. In Experiment 2, both sexes were fed balanced and unbalanced protein series, and at different rates, the slopes of the ascending part of the linear-plateau relationships for the different treatments were the same for all treatments (0.0204), and the inflection point was at 71 MJ AMEn/kg DCP. Using similar treatments in Experiment 3, the breakpoint for the balanced protein was 72 MJ/kg and for the unbalanced, 64, with a combined slope of 68 MJ AMEn/kg DCP. 3. The three experiments provide adequate evidence that ep is a linear-plateau function of the dietary AMEn:DCP ratio with a breakpoint of around 66.2 +/- 1.98 MJ AMEn/kg DCP. Below this critical ratio, food intake declines as does protein and lipid retention. 4. That broilers, like pigs, exhibit an energy-dependent phase when high-protein feeds are offered is of practical importance when formulating pre-starter feeds for broilers and starter feeds for turkey poults as the ep of such feeds may well fall below the maximum due to the lack of dietary energy required to process the high dietary protein contained in such feeds resulting in poorer performance than expected. PMID- 28990795 TI - Postprogression survival in patients with glioblastoma treated with concurrent chemoradiotherapy: a routine care cohort study. AB - Glioblastoma is the commonest malignant brain tumor in adults. Most patients develop progressive disease before they die. However, survival after developing progressive disease is infrequently reported. We identified patients with histologically proven disease who were treated with concurrent chemoradiotherapy during 2006-2013. We analyzed overall survival (OS), progression-free survival and postprogression survival (PPS) in relation to age, O6-methylguanine-DNA methyltransferase promoter methylation and extent of surgical resection. We identified 166 patients. Median survival was 13.5 months; 2-year OS was 21.7%. Median progression-free survival and PPS were 7.03 and 4.53 months, respectively. Age and extent of surgical resection were correlated with OS. Only the extent of surgical resection was associated with PPS. Our work suggests that the established prognostic factors for glioblastoma do not appear to help predict PPS. PMID- 28990800 TI - A robust analysis of hospital efficiency and factors affecting variability. AB - The objectives of this paper are to use data envelopment analysis to measure hospital inefficiency in a way that accounts for patient outcomes and to study the association between organizational factors, such as hospital-physicians integration level and teaching status, and market competition with hospital inefficiency. We apply the robust data envelopment analysis approach to a sample of private (both not-for-profit and for-profit) hospitals operating in the United States. Our data envelopment analysis model includes mortality and readmission rates as bad outputs and admissions, surgeries, emergency room, and other visits as good outputs. Therefore, our measurement of hospital inefficiency accounts for quality. We then use a subsampling regression analysis to determine the predictors of hospital inefficiency. For-profit, fully integrated and teaching hospitals were more efficient than their counterparts. Also hospitals located in more competitive markets were more efficient than those located in less competitive markets. Incorporating quality in the measurement of hospital efficiency is key for producing valid efficiency scores. Hospitals in less competitive markets need to improve their efficiency levels. Moreover, high levels of hospital physician integration might be instrumental in ensuring that hospitals achieve their efficiency goals. PMID- 28990801 TI - Furanone derivative and sesquiterpene from Antarctic marine-derived fungus Penicillium sp. S-1-18. AB - A new furanone derivative, butanolide A (1), and a new sesquiterpene, guignarderemophilane F (2), together with six known compounds, were isolated from the fungus Penicillium sp. S-1-18 derived from Antarctic marine. The new structures were determined by spectroscopic studies such as 1D- and 2D-NMR and MS analyses. The absolute configuration of 1 was determined by the modified Mosher's method, while the absolute configuration of 2 was determined by calculated ECD spectroscopy. The isolated secondary metabolites were evaluated for their protein tyrosine phosphatase 1B (PTP1B) inhibitory activity. Compound 1 showed moderate inhibitory activity against PTP1B with IC50 value of 27.4 MUM. PMID- 28990802 TI - Correction to: Cozzolino et al., Ovarian stimulation under the effect of isotretinoin. PMID- 28990804 TI - Effects of a blend of essential oils and overcrowding stress on the growth performance, meat quality and heat shock protein gene expression of broilers. AB - Overcrowding stress is common in the poultry industry. Chickens exposed to long term stressful situations are characterised by welfare impairment and immunosuppression. 1. The present study evaluated the effects of a blend of essential oils (EOB; cinnamaldehyde and thymol) and stocking density on the performance, gut microflora, meat quality and physiological stress markers of broilers. 2. One-day-old Ross 308 male broiler chickens (n = 360) were allocated to 4 experimental groups from d 22 to 42. Each treatment had 6 replicates of 15 chicks. Two groups were subjected to a high stocking density (HSD) of 20 birds/m2 and the other two groups were kept at a low stocking density (LSD) of 10 birds/m2. 3. The results of this study indicate that overcrowding stress decreased growth performance parameters, blood immunoglobulin (Ig)G and heterophil:lymphocyte (H:L) ratio but increased IgA and IgM levels. HSD reduced water-loss rate and pH decline at 45 min post mortem in the breast muscle. 4. Essential oils supplementation elevated H:L ratio but decreased breast meat redness and pH24. 5. Significant interactions between EOB and stocking density were observed for corticosterone (CS) level and mRNA levels of heat shock protein 70 (HSP70) in brain and heart. Although HSD increased CS and HSP70 when compared to LSD, the effects of the former were inconsistent with EOB supplemented diets. 6. In conclusion, dietary EOB supplementation could improve some of the biomarkers associated with overcrowding stress in broiler chickens. PMID- 28990805 TI - Experimental evidence for weaker endogenous inhibition of trigeminal pain than extra-trigeminal pain in healthy individuals. AB - Background and objectives The prevalence of pain syndromes that affect the territories innervated by the trigeminal nerve, such as headaches, is one of the highest and ranks second only to low back pain. A potential mechanism underlying this high prevalence may be a relatively weak endogenous pain modulation of trigeminal pain. Here, we sought to systematically compare endogenous pain modulation capabilities in the trigeminal region to those of extra-trigeminal regions in healthy subjects. Methods Healthy, pain free subjects (n = 17) underwent a battery of quantitative sensory testing to assess endogenous pain inhibition and pain enhancement efficiencies within and outside the trigeminal innervated region. Measurements included conditioned pain modulation (CPM), temporal summation of pain (TSP) and spatial summation of pain (SSP). Results Testing configurations that included trigeminal-innervated body regions displayed significantly weaker CPM when compared to extra-trigeminal innervated areas. SSP magnitude was smaller in the ophthalmic trigeminal innervation when compared to other body regions. TSP magnitude was not different between the different body regions tested. Conclusions Our findings point to regional differences in endogenous pain inhibition and suggest that in otherwise healthy individuals, the trigeminal innervation is subjected to a weaker inhibitory pain control than other body regions. Such weaker endogenous pain control could play, at least in part, a role in mediating the high prevalence of trigeminal-related pain syndromes, including primary headaches and TMD pain. PMID- 28990803 TI - New onset postoperative atrial fibrillation and early anticoagulation after cardiac surgery. AB - OBJECTIVES: New onset postoperative atrial fibrillation (POAF) after cardiac surgery is associated with increased risk for thromboembolic complications. Compliance with anticoagulation treatment is prerequisite for successful outcome after POAF. We hypothesized that a disciplined anticoagulation protocol initiated instantly after POAF secures a long-term outcome. DESIGN: A total of 519 consecutive patients undergoing cardiac surgery were retrospectively analyzed. Patients received anticoagulation using warfarin whenever POAF lasted longer than five min. Postoperative outcome including mortality, myocardial infarction and stroke were compared with patients on sinus rhythm (non-POAF). RESULTS: Mean age of the study cohort was 64.3 +/- 9.0 years and median follow-up time was 76 months. There were 177 (34%) POAF and 342 (66%) non-POAF patients. At discharge, 144 (81%) POAF patients complied with warfarin, while 82 (24%) non-POAF patients received warfarin for non-rhythm causes (p < .001). Mortality was higher in POAF as compared with non-POAF patients (p = .03). After adjustment for comorbidities, major adverse clinical events (MACE)- including a combination of late cardiovascular mortality, myocardial infarction, stroke and late atrial fibrillation- was independently associated with POAF (OR 2.73, 95%CI 1.69-4.45, p < .0001). CONCLUSIONS: POAF after cardiac surgery was associated with high risk of MACE. Early anticoagulation may be justified in POAF patients to secure a long term outcome after cardiac surgery. PMID- 28990806 TI - Optimizing the detection of biliary dysplasia in primary sclerosing cholangitis before liver transplantation. AB - BACKGROUND: Patients with primary sclerosing cholangitis (PSC) have increased risk of cholangiocarcinoma (CCA). We evaluated pre-transplant work-up in PSC patients, to search for the most effective strategy for the detection of biliary dysplasia or early CCA. METHODS: Two hundred and twenty five consecutive PSC patients undergoing liver transplantation (LTx) in Sweden between 1999 and 2013 were studied. Patients with CCA or dysplasia in the explanted liver were compared with those with benign histopathology. Measures of test performance were calculated for patients having brush cytology on one endoscopic retrograde cholangiopancreaticography (ERCP) occasion, for those having repeated examinations with or without cholangioscopy, and for fluorescence in situ hybridization (FISH). Survival after LTx was analyzed. RESULTS: Brush cytology on a single ERCP occasion had moderate sensitivity (57%) and high specificity (94%) for the detection of CCA/high grade dysplasia (HGD) in the explanted liver. The corresponding sensitivity and specificity for FISH were 84% and 90%, respectively. Utilizing repeated ERCP and brush cytology to confirm the initial finding improved sensitivity to 82%. Using single operator cholangioscopy (SOC) for targeted examination at the second ERCP improved sensitivity (100%) and specificity (97%) significantly. Mortality rate in patients with incidentally discovered CCA (n = 16) in the explanted liver was significantly higher than in patients with HGD or benign histopathology (HR 16.0; 95% CI, 5.6-45.4; p < .001). CONCLUSIONS: Repeated brush cytology especially when combined with targeted examination under SOC guidance is superior to single brush examinations. This strategy improves the detection of malignancy in PSC and is of importance for selection of patients for LTx. PMID- 28990807 TI - Process evaluation of Internet-based cognitive behavioural therapy for adults with tinnitus in the context of a randomised control trial. AB - OBJECTIVE: The research objective was to identify processes that could either facilitate or hinder clinical implementation of an Internet-based cognitive behavioural therapy intervention for tinnitus in the UK. This was done by exploring the research context, the intervention components and the factors that contributed to the outcomes obtained. DESIGN: This study investigated eight processes including the recruitment strategies, reach, research context, treatment dose delivered and received, implementation fidelity, barriers to implementation and effectiveness of the intervention. STUDY SAMPLE: Of the 169 registered participants, 146 were randomly assigned to the experimental or control groups (23 were excluded). The mean age was 55.57 years with an average tinnitus duration of 11.63 years. RESULTS: The intended sample of people with distressing tinnitus who were underserved with evidence-based tinnitus interventions was reached. The full guided intervention was delivered. The recommended modules were read more than the optional modules. Intervention components such as the easily readable format and the benefits of the applied relaxation programme facilitated significant positive post-intervention outcomes. Barriers hampering the intervention application included time pressures and low self-motivation. CONCLUSIONS: Results of this process evaluation together with the outcome data can be used to facilitate translating this research into clinical practice. PMID- 28990808 TI - MicroRNA-205 Mediates Proteinase-Activated Receptor 2 (PAR2) -Promoted Cancer Cell Migration. AB - Activation of proteinase-activated receptor 2 (PAR2) promotes cell migration in cancers, but the exact mechanism underlying this process remains largely unknown. Here we report that activation of PAR2 reduced miR-205 expression, whereas inhibition of miR-205 promoted cell migration in cancer cells. Overexpression of miR-205 blocked PAR2-mediated stimulation of cell migration. BMPR1B was identified as a downstream target gene of miR-205. In colorectal carcinoma specimens from patients, the level of PAR2 was negatively correlated with that of miR-205, but it was positively associated with BMPR1B expression. Taken together, our findings indicate that PAR2 signaling promotes cancer cell migration through miR-205/BMPR1B pathway in human colorectal carcinoma. PMID- 28990810 TI - CNS metastasis secondary to malignant-mixed Mullerian tumor: case report and review of therapeutics. AB - This paper reviews CNS involvement secondary to malignant-mixed Mullerian tumor or uterine carcinosarcoma, a rare aggressive biphasic Mullerian tumor. We report a cerebellar metastasis with epithelial and mesenchymal components, demonstrating heterologous rhabdomyogenic and chondroblastic differentiation. The patient had undergone total abdominal hysterectomy and bilateral salpingo-oophorectomy for palliation of symptomatic chemotherapy-resistant node-positive disease. CNS involvement is rare, and prognostically poor, and suggestively poorer in predominantly sarcomatous metastases. Multimodal therapy is indicated; in solitary metastases, surgical resection or stereotactic radiosurgery is included, followed by whole brain radiotherapy. In unresectable brain metastases, stereotactic radiosurgery and whole brain radiotherapy warrant consideration in up to 2-3 metastases. In multiple metastases, palliative steroid therapy or cranial irradiation may be considered. Combination or platinum-based chemotherapy (i.e., ifosfamide-paclitaxel or carboplatin-paclitaxel) is indicated in all stages, with a role in both disease cure and control-directed management. Targeted therapeutics have thus far not demonstrated significant clinical efficacy. PMID- 28990809 TI - Proteomic interrogation of HSP90 and insights for medical research. AB - INTRODUCTION: Heat shock protein 90 (HSP90) regulates protein homeostasis in eukaryotes. As a 'professional interactor', HSP90 binds to and chaperones many proteins and has both housekeeping and disease-related functions but its regulation remains in part elusive. HSP90 complexes are a target for therapy, notably against cancer, and several inhibitors are currently in clinical trials. Proteomic studies have revealed the vast interaction network of HSP90 and, in doing so, the extent of cellular processes the chaperone takes part in, especially in yeast and human cells. Furthermore, small-molecule inhibitors were used to probe the global impact of its inhibition on the proteome. Areas covered: We review here recent HSP90-related interactomics and total proteome studies and their relevance for research on cancer, neurodegenerative and pathogen diseases. Expert commentary: Proteomics experiments are our best chance to identify the context-dependent global proteome of HSP90 and thus uncover and understand its disease-specific biology. However, understanding the complexity of HSP90 will require multiple complementary, quantitative approaches and novel bioinformatics to translate interactions into ordered functional networks and pathways. Developing therapies will necessitate more knowledge on HSP90 complexes and networks with disease relevance and on total proteome changes induced by their perturbation. Most work has been done in cancer, thus a lot remains to be done in the context of other diseases. PMID- 28990811 TI - Evaluation of hospitalization costs and associated factors among maternity stays involving low-risk and moderate- to high-risk childbirths in the United States. AB - OBJECTIVES: This study aimed to assess the costs of childbirth and to identify factors associated with such hospital costs for low- and moderate/high-risk childbirth groups. METHODS: All hospitalizations for childbirth between 2010-2014 in the Premier Perspective Hospital Database were identified. Risk category for each birth was defined by the age of the subject and/or presence of specific maternal comorbidities and obstetric risk factors. Hospital childbirth costs were determined and stratified by risk groups. Factors associated with costs for each risk group were evaluated by multiple regression. RESULTS: Among 2,367,195 hospitalizations for childbirth, vaginal birth was the most common delivery method (n = 1,596,757; 68%). Among women characterized as moderate/high-risk, 42% (n = 642,495) had C-sections, while 11% (n = 90,211) of women categorized as low risk had C-sections. The proportion of women with serious maternal morbidity among moderate/high-risk vs. low-risk women was 2% (n = 29,496) vs. 0.3% (n = 2749), respectively. The mean costs for moderate/high-risk vs. low-risk hospitalizations were $6145 (median = $5760) and $5397 (median = $5001), respectively (p < 0.0001). Factors significantly associated with costs for moderate/high-risk hospitalizations included delivery type (C-section vs. vaginal birth), LOS, urban/rural hospital status, geographic regions, calendar year of hospitalization, teaching status, payer types and serious maternal morbidity. Similar factors were found to impact costs among low-risk hospitalizations. CONCLUSIONS: Characteristics such as delivery type, LOS, geographical region, teaching status, serious maternal morbidity and hospital urban/rural status were shown to impact hospital costs of childbirth. Screening and prevention strategies of factors that negatively impact costs may aid in reducing the hospitalization costs associated with childbirths. PMID- 28990812 TI - Transjugular intrahepatic portosystemic shunt treatment of variceal bleeding in an unselected patient population. AB - OBJECTIVE: To evaluate transjugular intrahepatic portosystemic shunt (TIPS) in variceal bleeding in a clinical setting. MATERIALS AND METHODS: Retrospective review of 131 patients (116 with liver cirrhosis) treated with TIPS with covered stent grafts in a single centre from 2002 to 2016. RESULTS: Survival at 1 and 2 years was 70% and 57% in patents with, and 100% at 2 years in patients without liver cirrhosis, respectively. A high Child-Pugh score and severe hepatic encephalopathy (HE) within 12 months post-TIPS were related to increased mortality. Re-bleeding occurred in 8% within 12 months and was related to TIPS dysfunction and a post-TIPS portosystemic gradient (PSG) of >=5 mmHg. The main cause of TIPS dysfunction was that the stent did not fully reach the inferior vena cava. There was no correlation between the PSG and the occurrence of HE. CONCLUSIONS: TIPS was safe and prevented re-bleeding in patients with variceal bleeding, with or without liver cirrhosis, regardless of Child-Pugh class and of how soon after bleeding onset, the TIPS procedure was performed. A post-TIPS PSG of >=5 mmHg was associated with an increased risk for re-bleeding and there was no correlation between the post-TIPS PSG and the occurrence of HE. PMID- 28990813 TI - Glioblastoma of pineal region: report of four cases and literature review. AB - We report four cases of glioblastoma in the pineal region. The patients presented a severe headache and vomiting. Brain imaging showed a heterogeneously enhanced tumor in the pineal region with obstructive hydrocephalus. Case 3 developed a subependymal dissemination. The patient went to ventricular-peritoneal shunt and subtotal or total resection and radiotherapy with/without chemotherapy. Cases 1 and 2 received radiation and died 8 and 11 later months. Cases 3 and 4 completed radiotherapy and chemotherapy, and survived 28 and 31 months after the initial diagnosis. Glioblastoma in the pineal region carry a poor prognosis and require neurooncology teams. PMID- 28990815 TI - Anti-inflammatory effect of ethanolic extract of spine, skin and rind of Jack fruit peel - A comparative study. AB - The present study was conducted to identify the chemical constituents and evaluate the anti-inflammatory activity of crude ethanolic extracts of spine, skin and rind of jack fruit (Artocarpus heterophyllus) peel. Polyphenol and flavonoid contents were assessed using Folin's Ciocalteu reagent and aluminium chloride methods which revealed 316, 355 and 382 mg tannic acid equivalent/g of polyphenol and 96.7, 131.6 and 164.6 mg quercetin equivalent/g of flavonoid in spine, skin and rind, respectively. Anti-inflammatory activity of all three extracts was comparable to diclofenac in vitro and in vivo studies. Skin exhibited maximum anti-inflammatory activity, rind had preferential inhibition on Cyclooxygenase-2 and spine and skin inhibited both Cyclooxygenase-1 and 2 in vitro. PMID- 28990817 TI - A combined liquid chromatography tandem mass spectrometry assay for the quantification of urinary oxalate and citrate in patients with nephrolithiasis. AB - Background Analysis of citrate and oxalate in a 24-h urine sample is important in the screening and monitoring of patients with nephrolithiasis. To streamline the analytical process, it was decided to combine oxalate and citrate and analyse them simultaneously in the same assay. Objective A highly sensitive and specific assay for analysis of urine citrate and oxalate was developed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with a simple weak anion exchange solid phase extraction (WAX SPE) clean-up procedure. Method Premixed calibrator/acidified urine (50 uL) was combined with mixed internal standard (13C2 oxalate/citrate-d4) and 5% v/v formic acid in water and passed through a Waters WAX SPE plate. After clean-up steps, the plate was eluted with 5% NH3 in methanol, the eluent was dried down and re-constituted with 100 uL distilled water. Separation was then performed on an HSS T3 2.1 * 50 mm column (Waters, Manchester, UK), flow rate of 0.5 mL/min using a gradient of aqueous and organic mobile phases. We detected multiple reaction monitoring transitions m/z citrate 191.1>110.9, citrate IS 195.1>112.9, oxalate 88.9>60.85, oxalate IS 90.9>61.9 using a Waters TQD in electrospray-negative mode. Results Oxalate and 13C2 oxalate were eluted at 0.29 min; citrate and citrate-d4 were eluted at 0.52 min. Mean recovery was 100% for oxalate and 103% for citrate; lower limit of quantification of oxalate was 60 umol/L and 50 umol/L for citrate. Oxalate was linear up to 1388 umol/L; citrate was linear up to 4762.5 umol/L. Oxalate was found to be affected by ion suppression (matrix effect: -23 to +65%) but was compensated for by the internal standard used in all cases. The coefficient of variation of the assay in urine for oxalate was <7% for oxalate and 5% for citrate. Discussion We have developed a rapid assay for LC-MS/MS measurement of urinary oxalate and citrate in a routine clinical laboratory. It is simple, reproducible and easy to perform. PMID- 28990814 TI - Induction of Anoikis in Human Colorectal Cancer Cells by Fucoxanthinol. AB - Fucoxanthin (Fx), one of the major xanthophylls in brown algae, is known to be effective for colorectal cancer (CRC) chemoprevention through inhibiting cell growth, cell cycle and caspase activation. Recently, we observed fucoxanthinol (FuOH), an anti-cancer active metabolite of Fx, treatment of human CRC cells resulted in plenty of living floating cells several hours after exposure, and induced apoptosis. In the present study, we investigated whether FuOH induced anchorage-dependent apoptosis, that is "anoikis", along with integrin signal suppression in human CRC cells. We found that cells exposed to 2.5 MUM FuOH clearly showed anti-proliferative and apoptotic effects to DLD-1 cells, human CRC cells. FuOH treatment of DLD-1 cells led to an increase in anoikis-like changes represented by Calcein AM negative/ethidium homodimer-1 positive cell and living floating cells. Moreover, FuOH decreased FAK activation, and altered integrin beta1 expression and distribution after 6 h treatment. After 24 h, the cells decreased PPARgamma expression and Akt activation and increased integrin beta1 expression. Our findings suggested that FuOH can induce anoikis in CRC cells through suppression of integrin signals in human CRC cells. PMID- 28990818 TI - Serum alpha-melanocyte-stimulating hormone may act as a protective biomarker for non-traumatic osteonecrosis of the femoral head. AB - Background The alpha-melanocyte-stimulating hormone (alpha-MSH), an endogenous neuropeptide derived from proopiomelanocortin (POMC), has been identified to suppress inflammation and prevent osteoblast damage. Objective The present study was aimed to investigate the role of serum alpha-MSH in non-traumatic osteonecrosis of the femoral head (ONFH). Methods Seventy-nine patients diagnosed with non-traumatic ONFH and 79 sex- and age-matched healthy controls were enrolled in the study. Serum alpha-MSH concentrations were examined with a double antibody radioimmunoassay. The radiographic progression of ONFH was assessed by X ray plain film according to the FICAT grading system. The symptomatic severity was evaluated by visual analogue scale scores, Harris hip scores and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores. The serum concentrations of protective marker adiponectin and bone necrosis inflammation factor IL-33 concentrations were also examined. The receiver operating characteristic (ROC) analysis curve was performed to explore the diagnostic value of alpha-MSH, adiponectin and IL-33 for radiographic progression. Results Serum alpha-MSH concentrations were significantly lower in ONFH patients than in healthy controls. The case group included 29 non-traumatic ONFH patients with FICAT grade I/II, 27 with grade III and 23 with grade IV. ONFH patients with grade I/II had significantly higher alpha-MSH concentrations in serum compared with those with FICAT grades III and IV. ONFH patients with FICAT grade III showed significantly elevated concentrations of alpha-MSH in serum compared with those with FICAT grade IV. Serum alpha-MSH concentrations were negatively associated with radiographic progression by FICAT grading system, and symptomatic severity defined by visual analogue scale scores, Harris hip scores and WOMAC scores. In addition, serum alpha-MSH concentrations were positively related to the expression of adiponectin and negatively associated with IL-33. ROC analysis curve demonstrated that alpha-MSH exhibited the equal value for the diagnosis of ONFH radiographic progression compared with IL-33. Conclusions Serum alpha-MSH may act as a protective biomarker for non-traumatic ONFH. Systematic application of alpha-MSH serving as an adjunctive therapy for treating non-traumatic ONFH deserves further investigation. PMID- 28990819 TI - Evaluating the U.S. Food Safety Modernization Act Produce Safety Rule Standard for Microbial Quality of Agricultural Water for Growing Produce. AB - The U.S. Food and Drug Administration (FDA) has defined standards for the microbial quality of agricultural surface water used for irrigation. According to the FDA produce safety rule (PSR), a microbial water quality profile requires analysis of a minimum of 20 samples for Escherichia coli over 2 to 4 years. The geometric mean (GM) level of E. coli should not exceed 126 CFU/100 mL, and the statistical threshold value (STV) should not exceed 410 CFU/100 mL. The water quality profile should be updated by analysis of a minimum of five samples per year. We used an extensive set of data on levels of E. coli and other fecal indicator organisms, the presence or absence of Salmonella, and physicochemical parameters in six agricultural irrigation ponds in West Central Florida to evaluate the empirical and theoretical basis of this PSR. We found highly variable log-transformed E. coli levels, with standard deviations exceeding those assumed in the PSR by up to threefold. Lognormal distributions provided an acceptable fit to the data in most cases but may underestimate extreme levels. Replacing censored data with the detection limit of the microbial tests underestimated the true variability, leading to biased estimates of GM and STV. Maximum likelihood estimation using truncated lognormal distributions is recommended. Twenty samples are not sufficient to characterize the bacteriological quality of irrigation ponds, and a rolling data set of five samples per year used to update GM and STV values results in highly uncertain results and delays in detecting a shift in water quality. In these ponds, E. coli was an adequate predictor of the presence of Salmonella in 150-mL samples, and turbidity was a second significant variable. The variability in levels of E. coli in agricultural water was higher than that anticipated when the PSR was finalized, and more detailed information based on mechanistic modeling is necessary to develop targeted risk management strategies. PMID- 28990820 TI - Interleukin 2 Secretion by T Cells for Detection of Biologically Active Staphylococcal Enterotoxin Type E. AB - Staphylococcus aureus is a significant worldwide source of clinical infections and foodborne illnesses; it acts through the synthesis of a group of enterotoxins (SEs) that cause gastroenteritis and also function as superantigens that activate T cells, resulting in massive cytokine production, yielding life-threatening toxicity. It is important that methods for detection and quantification of these toxins respond to their activity and not just the presence of the toxin molecule, which may be deactivated. Traditionally, live animals have been used to test for emesis following administration of the toxin-containing sample. Here, we present results studying cell-based alternatives for the assay of active staphylococcal enterotoxin type E (SEE), a toxin subtype identified in foodborne outbreaks in the United States, the United Kingdom, and France. We found that interleukin 2 production by T cells can be used as a specific biological marker for the quantitative detection of SEE as compared with subtypes SEA and SEB. Our assay shows a dose-response relationship between IL-2 secretion by Jurkat T-cell line and SEE concentration as low as 1 pg/mL. PMID- 28990821 TI - Enrichment Broth for the Detection of Campylobacter jejuni and Campylobacter coli in Fresh Produce and Poultry. AB - Although campylobacteriosis caused by Campylobacter jejuni and Campylobacter coli has been increasingly reported worldwide owing to the consumption of contaminated poultry and fresh produce, the current detection protocols are not selective enough to inhibit unspecific microbes other than these pathogens. Five antibiotics were separately added to Bolton broth, and the survival rates of 18 Campylobacter spp. and 79 non-Campylobacter spp. were evaluated. The survival rate of the non-Campylobacter spp. was the lowest in Bolton broth with rifampin (6.3%), followed by cefsulodin (12.7%), novobiocin (16.5%), and potassium tellurite and sulfamethozaxole (both 17.7%). Also the most effective concentration of rifampin was found to be 12.5 mg/L, which markedly inhibited non Campylobacter strains while not affecting the survival of Campylobacter strains. After the Campylobacter spp. were enriched in Bolton broth supplemented with 12.5 mg/L rifampin (R-Bolton broth), CampyFood Agar (CFA) was found to be better in selectively isolating the pathogens in the enrichment broth than the International Organization for Standardization method of using modified charcoal cefoperazone deoxycholate agar (mCCDA) for this step. When applied to natural food samples-here, romaine lettuce, pepper, cherry tomato, Korean leek, and chicken-the R-Bolton broth-CFA combination decreased the number of false-positive results by 50.0, 4.2, 20.8, 50.0, and 94.4%, respectively, compared with the International Organization for Standardization method (Bolton broth-mCCDA combination). These results demonstrate that the combination of R-Bolton broth and CFA is more efficient in detecting C. jejuni and C. coli in poultry and fresh produce and thus should replace the Bolton broth-mCCDA combination. PMID- 28990822 TI - Identification of Structural and Immunity Genes of a Class IIb Bacteriocin Encoded in the Enterocin A Operon of Enterococcus faecium Strain MXVK29. AB - The Enterococcus faecium strain MXVK29, isolated from fermented sausages, produces a bacteriocin with a molecular mass of 3.5 kDa that belongs to the class of enterocins II.1, according to the terminal amino acid sequence, and has been identified as enterocin A. This bacteriocin is active against selected strains of Listeria, Staphylococcus, Pediococcus, and Enterococcus. In this study, we identified the genes adjacent to the structural gene for this bacteriocin, such as the immunity gene (entI) and the inducer gene (entF). Accessory genes for this bacteriocin, such as entK, entR, and entT, were identified as well, in addition to the orf2 and orf3, showing a high identity with class IIb peptides bacteriocins. The orf2 shows the consensus motif GxxxG, similar to those shown by bacteriocins such as PlnNC8alpha, EntCalpha, and Ent1071A, whereas orf3 shows a consensus motif SxxxS similar to that present in PlnNC8beta (AxxxA). PlnNC8 is expressed only in bacterial cocultures, so there is the possibility that the expression of this two-peptide bacteriocin can be induced by a similar mechanism. So far, only the expression of enterocin A has been found in this strain; however, the presence of the genes ent29alpha and ent29beta opens the possibility for further research on its induction, functionality, and origin. Although there are reports on this type of bacteriocin (EntX, EntC, and Ent1071) in other strains of E. faecium, no report exists yet on an Enterococcus strain producing two different classes of bacteriocin. PMID- 28990823 TI - The Effectiveness of Suicide Prevention Education Programs for Nurses. AB - BACKGROUND: Education to improve health professionals' responses to suicide is considered an important suicide prevention strategy. However, the effectiveness of this approach for nurses is unclear. AIM: To systematically review the peer reviewed literature regarding the effectiveness of suicide prevention education programs for nurses. METHOD: Nine academic databases (CINAHL, Cochrane Reviews & Trials, Embase, Informit Health Collection, Joanna Briggs Institute, Medline, PsycINFO, Scopus, and Web of Science) were searched in November 2016, utilizing search terms related to suicide, education, and nurses, with no limits placed on publication date or study design. RESULTS: The search yielded 5,456 identified articles, 11 of which met the inclusion criteria. Studies were primarily quantitative (RCTs n = 3; quasi-experimental n = 6; qualitative n = 2), and involved nurses (range = 16-561) working in a diversity of settings, particularly hospitals (n = 9). Studies revealed positive changes in nurses' competence, knowledge, and attitudes associated with training over the short term. LIMITATIONS: The heterogeneity of education programs and methodological weaknesses of included studies limit the conclusions drawn. CONCLUSION: There is a moderate body of evidence to support the effectiveness of suicide prevention education programs for nurses. Future research should examine longer-term changes in clinical practice and strategies for continuing education, with more rigorous study designs. PMID- 28990825 TI - Perceived Stress and Intent to Die in Young Soldiers Who Attempt Suicide. AB - BACKGROUND: Intent to die is an important component of suicide risk assessment. The authors compared the predictive effect of two forms of stress - military and perceived - in intent to die by suicide among young adult Israeli soldiers with a history of suicide attempts. Depression, suicide ideation, and habituation/acquired capacity for suicidality served as covariates. METHODS: Participants were 60 young adult soldiers in the Israeli Defense Force (ISF; aged 18-21 years), who made a suicide attempt during their military service. Study variables were assessed using self-report measures. RESULTS: Intent to die by suicide correlated with suicide ideation, habituation/acquired capacity, depressive symptoms, and perceived stress. In a multiple regression analysis, perceived stress predicted intent to die (b = .44, p = .002) over and above the prediction by suicide ideation (b = .42, p = .013) and acquired capacity/habituation (b = .28, p = .023). LIMITATIONS: The cross-sectional design restricts causal inference. In addition, an exclusive reliance on self-report measures might have inflated shared method variance. CONCLUSIONS: Perceived stress captures a unique dimension of intent to die by suicide among young suicide attempters. PMID- 28990824 TI - Where Are They Now? AB - BACKGROUND: While a history of suicide attempts has been identified as the most powerful risk factor among adults, it is not clear if this is also true for the adolescent population. Our aim was to examine the differences between attempters and nonattempters in the years following a documented suicide attempt and to investigate the adolescents' prognosis in terms of suicidal behavior and adjustment. METHOD: Military records at induction and during active military service were used to compare 105 adolescent suicide attempters with 105 matched controls. All were rated on cognitive/educational performance and psychosocial adaptation, psychological health diagnoses, and performance during their military service. RESULTS: Suicide attempters had higher school dropout rates and lower scores on educational indicators. They registered more incidents of disciplinary and adjustment problems in the military. However, the overall prognosis of the suicide attempters appeared surprisingly good. No significant differences were found between the groups in suicide risk or in behavior in their military service. LIMITATIONS: Data were derived from the computerized records and no direct interviews were conducted with the participants. CONCLUSION: Attempted suicide in adolescence appears to be different in nature from attempted suicide in adulthood, and can be viewed as an indicator of social distress rather than as major risk factor of completed suicide. Implications in terms of intervention and prevention are discussed. PMID- 28990826 TI - Undergraduate Students' Exposure, Knowledge, Utilization, and Intended Use of the National Suicide Prevention Lifeline. AB - BACKGROUND: Suicide is a leading cause of death among college students. Crisis hotlines play a role in linking suicidal individuals to help. Despite leading to favorable outcomes, low utilization of crisis outlines has been reported. AIMS: To explore exposure, knowledge, and utilization of the National Suicide Prevention Lifeline (NSPL) among a sample of university students; to determine if knowledge and perceived helpfulness of NSPL predict intent to use NSPL. METHOD: The researcher surveyed 560 students attending a Midwestern university to assess knowledge of, and attitudes toward, the NSPL. RESULTS: Those who reported seeing the NSPL advert (50%) perceived the NSPL to be more helpful than those who had not seen the advert. Only 29% (n = 160) were able to identify who would answer the NSPL (a trained, skilled counselor). Only 1% (n = 4) reported utilization. Participants who reported past exposure to the NSPL advert reported higher levels of perceived helpfulness of the NSPL. Perceived helpfulness of the NSPL was a weak predictor of likelihood to use the NSPL. LIMITATIONS: The study limitations include its small sample size; participants' likelihood to use the NSPL was assessed using independent symptoms. CONCLUSION: Further research is needed to identify college students' underlying attitudes toward the NSPL. PMID- 28990827 TI - Ural Eye and Medical Study: description of study design and methodology. AB - PURPOSE: Since there is a scarcity on population-based health information available for Russia, we conducted this project to assess the prevalence of major ocular and systemic disorders and their associated risk factors. METHODS: A population-based cross-sectional study (Ural Eye and Medical Study (UEMS)) was performed in Bashkortostan 1300 km east of Moscow. The sampling frame consisted of all inhabitants aged over 40 years and living in an urban study area in the capital city Ufa and a rural region at 65 km outside of Ufa. The target sample size was 2500 individuals for the urban region and 2500 persons for the rural region. The study participants underwent a detailed interview, a detailed ophthalmologic examination including biometry and optical coherence tomography, and clinical examination including assessment of electrocardiography, hearing test, blood sampling, spirometry, and hand grip dynamometry. RESULTS: After a first study period, the study population included 4254 individuals with a mean age of 60.3 +/- 11.1 years (range: 40-94 years), mean body weight of 74.8 +/- 14.4 kg (range: 31-170 kg), body height of 163.6 +/- 8.9 cm (range: 112-196), body mass index of 28.0 +/- 5.1 kg/m2 (range: 13.96-60.96 kg/m2), mean systolic blood pressure of 133.7 +/- 21.0 mmHg (range: 84-232 mmHg), and mean diastolic blood pressure of 81.2 +/- 10.6 mmHg (range: 40-134 mmHg). Mean refractive error was -0.21 +/- 1.94 D and mean intraocular pressure was 13.6 +/- 3.9 mmHg. CONCLUSIONS: The UEMS provides population-based normative data for a Russian region on the quantitative traits such as axial length, quality of life and lifestyle including smoking and alcohol consumption, and prevalence and risk factors of ocular and systemic diseases such as diabetes mellitus, arterial hypertension, chronic obstructive pulmonary disease, and depression. PMID- 28990828 TI - Radiologic features of vascular pulsatile tinnitus - suggestion of optimal diagnostic image workup modalities. AB - OBJECTIVES: The aim of this study was to determine the optimal diagnostic workup modalities for vascular pulsatile tinnitus through analysis of clinical and radiologic findings. MATERIALS AND METHODS: A total of 49 patients diagnosed with vascular pulsatile tinnitus along with their medical records and radiologic findings were thoroughly reviewed. RESULTS: Of these patients, 84% had venous lesions. The jugular bulb variants (67%) were the most common venous lesions followed by sigmoid sinus variants (12%). About 88% (43/49) of these lesions were detected with computed tomography of the temporal bone (TBCT) alone and the lesions were either venous or intratemporal artery in origin. Simple manual neck compression test was 93% sensitive in predicting venous lesions. A high suspicion for venous lesion coupled with manual neck compression test and selection of the optimal imaging technique are useful for the proper evaluation of vascular pulsatile tinnitus at the initial visit. CONCLUSION: Our stepwise strategy may increase the cost-effectiveness of the chosen imaging workup by reducing redundancy of multiple and simultaneous radiologic tests in patients with vascular pulsatile tinnitus. PMID- 28990829 TI - Diplopia after Cataract Extraction. AB - Diplopia after cataract extraction is an unexpected outcome for the patient and often a source of confusion for the physician, owing to its relative infrequency. This article reviews the pertinent literature on the subject. Mechanisms include anesthetic myotoxicity, surgical trauma, optical aberrations, cortical disorders in patients with congenital strabismus, and the unmasking of previously unnoticed ocular misalignment. As the population continues to age and cataract extraction is performed in increasing volume, familiarity with this uncommon but important outcome may help to clarify and effectively treat post-cataract-extraction diplopia. PMID- 28990831 TI - The patient-centered medical home model: healthcare services utilization and cost for non-elderly adults with mental illness. AB - BACKGROUND: The patient-centered medical home (PCMH) model is designed to improve health outcomes while containing the cost of care. However, the evidence is inconclusive. AIMS: The aim of this study was to examine the associations between receipt of care consistent with the PCMH and healthcare services utilization and expenditures for non-elderly adults with mental illness in the USA. METHOD: A surveillance study was conducted using self-reported data for 6908 non-elderly adults with mental illness participating in the 2007-2012 Medical Expenditure Panel Survey. Healthcare services utilization and expenditures were compared for study participants who received care consistent with the PCMH, participants with a non-PCMH usual source of care (USC), and participants without a USC. RESULTS: Differences in utilization and expenditures between participants who received care consistent with the PCMH and participants who had a non-PCMH USC were not statistically significant for any healthcare services category. CONCLUSIONS: Receipt of care consistent with the PCMH was not significantly associated with differences in healthcare services utilization or expenditures compared to having a non-PCMH USC. Research assessing whether the PCMH is cost-effective for non elderly adults with mental illness is needed. PMID- 28990830 TI - Value of pulse oximetry watch for diagnosing pediatric obstructive sleep apnea/hypopnea syndrome. AB - OBJECTIVE: To evaluate the clinical value of pulse oximetry watch (POW) for diagnosing pediatric Obstructive sleep apnea/hypopnea syndrome (OSAHS). METHODS: We selected 32 children (boys: 25, 4-16 years old) who came to the hospital for diagnosing OSAHS from July to October 2016. Polysomnography (PSG) and POW were used simultaneously and recorded the apnea hypopnea index (AHI), LSpO2, and ODI4. Pearson analysis, t test, and receiver-operating characteristic (ROC) were used to analyze the correlation between PSG-AHI and other indicators, the diagnosis accordance rate, and the sensitivity and specificity of POW, respectively. RESULTS: According to PSG-AHI, 32 children were divided into two groups: primary snoring (n = 5) and OSAHS (n = 27). There was no significant difference between PSG-ODI4 and POW-ODI4 (p > .05). A statistically significant correlation between PSG-AHI and POW-ODI4 was found (r = .719, p < .001). When PSG-AHI >1, 5, 10, 15, and 20 events/h, the area under the curve (AUC) was 0.685 (p > .05), 0.733, 0.798, 0.922, and 0.929 (p < .05), respectively. There were high levels of sensitivity (83.33%) and specificity (92.31%) in the OSAHS with AHI >20 events/h level, whereas the sensitivity and specificity were unacceptable (<75%) at the level of AHI >1, 5, 10, and 15 events/h. CONCLUSIONS: POW cannot replace PSG to diagnose pediatric OSAHS because of low sensitivity and specificity, but can be used for screening severe OSAHS in children. PMID- 28990832 TI - Complex interplays between phytosterols and plastid development. AB - Isoprenoids comprise the largest class of natural compounds and are found in all kinds of organisms. In plants, they participate in both primary and specialized metabolism, playing essential roles in nearly all aspects of growth and development. The enormous diversity of this family of compounds is extensively exploited for biotechnological and biomedical applications as biomaterials, biofuels or drugs. Despite their variety of structures, all isoprenoids derive from the common C5 precursor isopentenyl diphosphate (IPP). Plants synthesize IPP through two different metabolic pathways, the mevalonic acid (MVA) and the 2-C methyl-D-erythritol 4-phosphate (MEP) pathways that operate in the cytosol-RE and plastids, respectively. MEP-derived isoprenoids include important compounds for chloroplast function and as such, knock-out mutant plants affected in different steps of this pathway display important alterations in plastid structure. These alterations often lead to albino phenotypes and lethality at seedling stage. MVA knock-out mutant plants show, on the contrary, lethal phenotypes already exhibited at the gametophyte or embryo developmental stage. However, the recent characterization of conditional knock-down mutant plants of farnesyl diphosphate synthase (FPS), a central enzyme in cytosolic and mitochondrial isoprenoid biosynthesis, revealed an unexpected role of this pathway in chloroplast development and plastidial isoprenoid metabolism in post-embryonic stages. Upon FPS silencing, chloroplast structure is severely altered, together with a strong reduction in the levels of MEP pathway-derived major end products. This phenotype is associated to misregulation of genes involved in stress responses predominantly belonging to JA and Fe homeostasis pathways. Transcriptomic experiments and analysis of recent literature indicate that sterols are the cause of the observed alterations through an as yet undiscovered mechanism. PMID- 28990833 TI - Prevalence of restless legs symptoms according to depressive symptoms and depression type: a cross-sectional study. AB - BACKGROUND: Restless legs syndrome is a sensorimotor disorder and it is associated with several other diseases especially mental illnesses. AIMS: To analyze the relationship between the symptoms of restless legs syndrome and the severity of depressive symptoms and the prevalence of restless legs symptoms in depression subtypes. METHODS: A cross-sectional study of primary care patients in the Central Finland Hospital District. The prevalence of restless legs symptoms was studied in 706 patients with increased depressive symptoms and 426 controls without a psychiatric diagnosis by using a structured questionnaire. The depressive symptoms were evaluated with the Beck Depression Inventory (BDI) and the psychiatric diagnosis was confirmed by means of a diagnostic interview (Mini International Neuropsychiatric Interview). The subjects with increased depressive symptoms were divided into three groups (subjects with depressive symptoms without a depression diagnosis, melancholic depression and non-melancholic depression). RESULTS: In the whole study population, the prevalence of restless legs symptoms increased with the severity of depressive symptoms. The prevalence of restless legs symptoms was highest in the melancholic and non-melancholic depressive patients (52 and 46%, respectively) and then in subjects with depressive symptoms without a depression diagnosis (43.4%), but the prevalence was also substantial (24.6%) in subjects without a psychiatric diagnosis. CONCLUSIONS: Restless legs symptoms are very common in primary care among subjects with depression, regardless of the depression type. The prevalence of restless legs symptoms increased with increasing severity of depressive symptoms, regardless of the diagnosis. These findings should be considered in clinical evaluation and treatment of patients visiting their physician due to restless legs or depressive symptoms. PMID- 28990834 TI - Eustachian tube evaluation in patients with obstructive sleep apnea syndrome. AB - OBJECTIVES: Investigate the presence of Eustachian Tube Dysfunction (ETD) in Obstructive sleep apnea (OSA) patients. Correlate the ET function and the severity of the sleep apnea syndrome. Correlate nasal resistance and nasal mucociliary clearance with the onset of ETD in these patients. MATERIALS AND METHODS: Forty patients affected by OSA were enrolled in our clinical prospective study. Thirty patients were also investigated as a control group. All of the analyzed subjects underwent ENT examination, anterior rhinomanometry and test for mucociliary transport time. To evaluate Eustachian tube function the Eustachian tube score-7 (ETS-7) were employed. RESULTS: Twenty percent of the patients with a diagnosis of OSA had a diagnosis of ETD (ETS-7 <= 7) with a statistical difference with control group (p = .03). No differences regarding ETD in OSA sub groups were found. CONCLUSION: This study showed that ET blockage or delayed openings were found in most adult patients with OSA when evaluated by a sensible score as the ETS-7. Our data suggest that an evaluation of the Eustachian tube function should be performed in patients suffering from obstructive sleep apnea syndrome. PMID- 28990836 TI - Images from the Dental Illustration Unit at Leeds Teaching Hospitals NHS Trust. PMID- 28990835 TI - Children exposed to a natural disaster: psychological consequences eight years after 2004 tsunami. AB - BACKGROUND: There is a need for studies that follow up children and adolescents for many years post disaster since earlier studies have shown that exposure during natural disasters constitutes a risk factor for poor psychological health. AIMS: The main aim was to examine whether there was an association between severity of exposures during a natural disaster experienced in childhood or adolescence and posttraumatic stress symptoms, psychological distress, self-rated health, diagnosis of depression, anxiety or worry, thoughts about or attempted suicide, physical symptoms or daily functioning eight years later in young adulthood. A second aim was to compare psychological distress and self-rated health of exposed young adults with a matched population-based sample. METHOD: Young adults, who experienced the 2004 tsunami as children between 10 and 15 years of age, responded to a questionnaire eight years post disaster. The results were compared to a matched population sample. RESULTS: The results showed that the likelihood for negative psychological outcomes was higher for those who had been exposed to several types of exposures during this natural disaster. CONCLUSIONS: The negative psychological impact on children and adolescents can still be present eight years post-disaster and seems to have association with the type of exposure; loss, physical presence and subjective experience. It is important for clinicians, who meet young adults seeking help, to be conscious about the impact as long as eight years post disaster and to be aware of possible clinical implications associated with severity of exposures. PMID- 28990837 TI - Quercetin nanoparticles alter pharmacokinetics of bromocriptine, reflecting its enhanced inhibitory action on liver and intestinal CYP 3A enzymes in rats. AB - 1. Quercetin is a dietary flavonoid has extremely low water solubility and found to possess CYP3A inhibitory activity. The purpose of the present study was to evaluate the effect of quercetin and quercetin nanoparticles (NQC) on the pharmacokinetics of bromocriptine (BRO) in rats. 2. NQC prepared by antisolvent precipitation method and characterized by SEM and dissolution test. The following methods were used in this study i.e. in vitro liver and intestinal CYP3A microsomal activity and in vitro non-everted sac method. To confirm these findings, an in vivo pharmacokinetic study was also performed. 3. The results indicate that quercetin significantly (p < 0.05) inhibited the CYP3A activity in liver and intestinal microsomes. In non-everted sac study, the intestinal transport and Papp of BRO were significantly increased in NQC and quercetin groups. Furthermore, in vivo study revealed that the increased levels of Cmax and AUC were comparatively high in NQC pretreated group than quercetin group. In addition, pretreatment with quercetin and NQC significantly (p < 0.05) decreased the mean CL/F and Vd/F of BRO. 4. NQC pretreatment might be result in higher plasma levels of quercetin that could inhibit the CYP3A enzyme and enhanced the bioavailability of BRO. PMID- 28990838 TI - 3D Printing Calcaneal Fractures: Continuously Improving our Care by Making a Complex Problem Tangible. AB - Calcaneal fractures are amongst the most complex injuries known to man. Their intricate anatomy and extensive damage after trauma make them difficult to understand and treat. Most surgeons specialized in foot and ankle trauma agree that in most patients surgical managements yields the best result. Functional outcome is largely dependent on preventing complications and restoring anatomy. Reconstruction of height and suntalar joint congruency for example are both associated with improved outcome. Over the years insight in the complex (patho )anatomy has increased. First by conventional radiographs, later with computed tomography. Recently 3D scans and prints have been added to this armamentarium. The study in the current issue of the Journal of Investigative Surgery explores the use of 3D printed calcaneal fractures and the effect on restoring anatomy and functional outcome. An invited short commentary was provided. PMID- 28990839 TI - A review of intelligent systems for heart sound signal analysis. AB - Intelligent computer-aided diagnosis (CAD) systems can enhance the diagnostic capabilities of physicians and reduce the time required for accurate diagnosis. CAD systems could provide physicians with a suggestion about the diagnostic of heart diseases. The objective of this paper is to review the recent published preprocessing, feature extraction and classification techniques and their state of the art of phonocardiogram (PCG) signal analysis. Published literature reviewed in this paper shows the potential of machine learning techniques as a design tool in PCG CAD systems and reveals that the CAD systems for PCG signal analysis are still an open problem. Related studies are compared to their datasets, feature extraction techniques and the classifiers they used. Current achievements and limitations in developing CAD systems for PCG signal analysis using machine learning techniques are presented and discussed. In the light of this review, a number of future research directions for PCG signal analysis are provided. PMID- 28990840 TI - Stereoselective in vitro metabolism of rhynchophylline and isorhynchophylline epimers of Uncaria rhynchophylla in rat liver microsomes. AB - 1. The objective was to investigate the underlying mechanism of the stereoselectivity in the metabolism of rhynchophylline (RIN) and isorhynchophylline (IRN) epimers in rat liver microsomes (RLM). 2. After incubation, eight metabolites of RIN (M1-5) and IRN (M6-8) reacted at A- and C ring were identified using LC-Q-TOF/MS. Metabolic pathways included oxidation, hydroxylation, N-oxidation and dehydrogenation. In addition, hydroxylation at A ring was the major metabolic pathway for RIN whereas the oxidation at C-ring was the major one for IRN. 3. Enzyme kinetics showed that the intrinsic clearance (CLint) for IRN elimination was 1.9-fold higher than RIN and the degradation half life (T1/2) of RIN was 4.7-fold higher than that of IRN, indicating IRN was more favorable to be metabolized than RIN in RLM. 4. Data from chemical inhibition study demonstrated CYP3A was the predominant isoform involved in the metabolic elimination of both epimers, as well as the formation of M1-8. 5. In conclusion, data revealed that due to the spatial configurations at C-7 position, RIN and IRN epimers possessed different hepatic metabolic pathways and elimination rates which were mainly mediated by CYP3A. PMID- 28990841 TI - Utilization patterns of systemic corticosteroid use for chronic rhinosinusitis. AB - OBJECTIVE: We sought to characterize the utilization pattern and factors associated with use of systemic corticosteroids for CRS. METHODS: This was a cross-sectional study of 236 participants with CRS who were prospectively recruited. Participants reported the number of CRS-related oral corticosteroid courses taken in the last year. Baseline CRS symptomatology was measured using the 22-item Sinonasal Outcome Test (SNOT-22) and SNOT-22 sleep, nasal, otologic/facial pain and emotional subdomain scores. Clinical and demographic characteristics were also collected. Association was determined between patient characteristics and oral corticosteroid use in the last year for CRS. RESULTS: Sleep (p = .026), nasal (p < .001) and otologic/facial pain (p = .022) SNOT-22 subdomain scores, and nasal polyps (p = .007) were associated with CRS-related oral corticosteroid use. In study participants without polyps, past CRS-related oral corticosteroid use was associated with sleep (adjusted OR = 1.56, 95%CI: 1.01-2.40, p = .043), otologic/facial pain (adjusted OR = 1.65, 95%CI: 1.09-2.51, p = .019) and nasal subdomain scores (adjusted OR = 1.59, 95%CI: 1.01-2.51, p = .047). In study participants with polyps, past CRS-related oral corticosteroid use was only associated with the nasal subdomain score (adjusted OR = 2.20, 95%CI: 1.40-3.45, p = .001). CONCLUSIONS: Past CRS-related oral corticosteroid use was associated with increased baseline severity of specific symptoms, which were different depending on the presence of polyps. PMID- 28990842 TI - MicroRNA-655-3p regulates Echinacea purpurea mediated activation of ABCG2. AB - 1. The aim of this study was to investigate the regulatory effect of Echinacea purpurea (EP) on efflux transporters ABCB1 and ABCG2 and to identify specific microRNAs contributing to their post-transcriptional regulation. 2. ABCB1 and ABCG2 levels were assessed in human hepatoblastoma HepG2 cells treated with 50 ug/mL methanolic extract of commercial EP capsules for different durations. The microRNA expression profile of HepG2 cells after EP treatment was evaluated and in silico target prediction was subsequently conducted to identify specific microRNAs with binding sites in the 3'-UTR of ABCB1 and ABCG2. Luciferase reporter gene assays and site-directed mutagenesis were used to confirm the binding site of identified microRNA within the 3'-UTR of the target gene. 3. EP increased ABCB1 (10-fold +/- 3.4, p < 0.001) and ABCG2 (2.7-fold +/- 0.5, p < 0.01) mRNA levels after 12 h exposure. Twenty-four microRNAs showed significant expression differences at all durations of exposure to EP. MiR-655-3p showed a 6.79-fold decrease in expression after 12 h exposure compared to 0 h, was predicted in silico to bind ABCG2 3'-UTR and showed a significant negative correlation (p = 0.01) to ABCG2 expression level. The binding of miR-655-3p to ABCG2 3'-UTR was confirmed by reporter gene assays (reduction of reporter gene activity to 60%; p = 0.0001). 4. These results suggest that EP regulates ABCG2 expression via downregulation of miR-655-3p in the liver cells. Thus, miR-655-3p downregulation could be applied to predict EP mediated drug interactions. PMID- 28990843 TI - Tackling exam-induced anxiety at medical school. PMID- 28990844 TI - Impact of nasal conditions on chronic otitis media: a cross-sectional study in Koreans. AB - OBJECTIVES: We evaluated the relationship between pathological nasal conditions and pathological middle ear conditions on a large-scale epidemiological basis, conducted as a cross-sectional study at the population level using Korean National Health and Nutrition Examination Survey (KNHANES) data. STUDY DESIGN: A cross-sectional study. METHODS: In a retrospective cohort study, we analyzed data from the KNHANES (2008-2012), which used a stratified, multi-stage, probability cluster sampling method in a rolling sampling survey of South Korean citizens. RESULTS: The prevalences of nasal and middle ear pathologies were evaluated. Chronic postnasal drip, chronic hypertrophic rhinitis, and nasal polyps were correlated with the presence of middle ear pathologies; allergic rhinitis was negatively correlated. The prevalences of chronic otitis media and septal deviation showed no relationship. Only nasal polyps showed a tendency to be associated with cholesteatomatous otitis media in patients with COM. CONCLUSIONS: Our results indicate the need for a nasal assessment when evaluating COM. Additionally, correction of nasal pathologies may be useful with the surgical treatment of COM to improve patient success rates and satisfaction. PMID- 28990845 TI - The relationship between red cell distribution width and the risk of Henoch Schonlein purpura nephritis. AB - INTRODUCTION: Red blood cell distribution width (RDW) is elevated in various inflammatory diseases, but its clinical significance in Henoch-Schonlein purpura nephritis (HSPN) in unknown. The aim of this study was to determine the value of RDW as a risk factor or marker for HSPN in children. METHODS: This was a case control study of 105 Henoch-Schonlein purpura (HSP) patients, 120 HSPN patients and 192 healthy controls. The relationship between RDW-coefficient of variation (RDW-CV) and the clinical characteristics of HSPN patients was determined by a multiple logistic regression analysis (MVLRA). Receiver operating characteristic (ROC) curves were applied to compare the diagnostic potential of the RDW-CV, a panel of routine markers and combinations of these indices. RESULTS: The RDW-CV values were significantly higher in the HSPN group than the HSP group and controls (P < 0.001). Significant correlations were found between RDW-CV and ESR (P = 0.001). A combination of RDW-CV and ESR in a ROC curve showed 80% sensitivity and 84.9% specificity in the HSP patients, and 85.8% sensitivity and 93.8% specificity in the HSPN patients. The MVLRA revealed that RDW-CV (OR 1.69, 95% CI 1.16-2.48, P = 0.007) was an independent predictor of HSPN. CONCLUSIONS: The RDW levels were highest in the HPSN group, suggesting that RDW, especially the combination of RDW and ESR, may have value when assessing the risk of HSPN. PMID- 28990846 TI - Aldehyde dehydrogenases may modulate signaling by lipid peroxidation-derived bioactive aldehydes. AB - Aldehyde molecules were shown to induce gene expression but because of their toxicity, the cell expresses ALDEHYDE DEHYDROGENASES (ALDH, EC 1.2.1.3) that oxidize them to carboxylic acids. To understand how the aldehydes may be both toxic and gene activators, we expressed the ALDH7B4 gene promoter fused to the beta-glucuronidase reporter gene in independent transgenic lines and found that pentanal and trans-2-hexenal activated the promoter whereas trans-2-hexenal induced the ALDH7B4 protein. Paraquat led to higher amounts of malondialdehyde compared to trans-2-hexenal and H2O2, and only the treatment by Paraquat activated the ALDH7B4 promoter, indicating that a threshold level of aldehydes is required for gene activation. These findings suggest that ALDH activity may also serve to fine-tune gene activation by the aldehydes. PMID- 28990847 TI - Obstructive sleep apnoea: from respiratory events to coronary microvascular dysfunction. AB - Obstructive sleep apnoea (OSA) is an emerging and independent risk factor for cardiovascular diseases; coronary artery disease (CAD) is higher in OSA patients, even in the absence of other traditional cardiovascular risk factors. There is little evidence to show abnormalities in coronary blood flow (CBF) and disorders in coronary vascular resistance (CVR), occurring during the obstructive respiratory event, suggesting coronary microvascular dysfunction (CMD) as a potential mechanism of ischaemic heart disease (IHD) OSA-as a related consequence. PMID- 28990848 TI - Enhancement of the Therapeutic Effect of Albendazole on Cystic Echinococcosis using a Herbal Product. AB - PURPOSE: Albendazole is the drug of choice for chemotherapy of cystic echinococcosis (CE) but 40% of patients do not respond to it satisfactorily. With regard to the previously reported scolicidal activity of Zataria multiflora, this study was done to evaluate the efficacy of the co-administration of albendazole and Z. multiflora aromatic water (AW) on hydatid cysts in a murine model. MATERIALS AND METHODS: Laboratory mice were infected with 1,500 viable protoscoleces. After development of hydatid cysts, the infected mice were allocated into four treatment and one control group. The mice of groups 1, 2, 3, and 4 were treated orally with albendazole (100 mg/kg), Z. multiform AW (100 ml/l), albendazole (100 mg/kg) - Z. multiform AW and albendazole ((50 mg/kg) - Z. multiform AW respectively. Two months later, all the mice were euthanized and necropsied and the number, size and weight of hydatid cysts were compared between different groups. RESULTS: The size of the largest cysts, as well as the total weight of cysts, were significantly lower (p < .05) in the mice treated with albendazole (50 mg/kg) - Z. multiflora AW in comparison to those treated with albendazole (100 mg/kg) alone. CONCLUSIONS: The results of this study revealed the superiority of co-administration of albendazole and Z. multiflora AW to albendazole alone in the treatment of CE in laboratory mice. Since Z. multiflora AW is a safe and useful drink, it may be used successfully to enhance the therapeutic effect of albendazole in the patients infected with hydatid disease. PMID- 28990849 TI - How was hidden-curriculum teaching enhanced? A question to Zhang et al. PMID- 28990851 TI - Stability study of a clonidine oral solution in a novel vehicle designed for pediatric patients. AB - Clonidine hydrochloride is administered to opioid-addicted mothers' neonates to reduce neonatal abstinence syndrome. It is prescribed off-label to neonates at 0.5-1 ug/kg/6 h, alone or in combination. The commercially injectable form of clonidine-Catapressan(r) 0.15 mg/mL-is being orally given after an appropriate dilution in water. However, this practice is not suitable for a perfectly safe and accurate administration. The objectives were to design a 10 ug/mL oral solution of clonidine hydrochloride in Inorpha(r) and to study the stability of this solution by a validated stability-indicating liquid chromatography (LC) method. The chemical, physicochemical and microbiological stability of the compounded formulation stored at 5 +/- 3 degrees C and 25 +/- 2 degrees C was tested over 60 days. The LC method used is specific, linear, accurate and precise. Upon storage between 2 and 8 degrees C according to classical and 'in use' schedules, the concentrations of clonidine and potassium sorbate (preservative) were found to be between 90.0 and 110.0% of the initial concentration, the pH between 4.4 and 4.7 and no microbial growth was noted. The stability of clonidine hydrochloride oral solution in Inorpha(r) sets the basis for individualized, easy and safe administration of clonidine in pediatric populations. PMID- 28990850 TI - The relationship between Toxoplasma gondii IgG antibodies and generalized anxiety disorder and obsessive-compulsive disorder in children and adolescents: a new approach. AB - AIM: Toxoplasma gondii may play a role in the development of psychiatric diseases by affecting the brain. The purpose of this study was to examine the relation between serum toxoplasma IgG positivity and obsessive-compulsive disorder (OCD) and generalized anxiety disorder (GAD) in children and adolescents. METHOD: Sixty patients diagnosed with OCD and 60 patients with GAD presenting to the pediatric psychiatry clinic, together with 60 control group subjects with no psychiatric diagnosis, were included in the study. The patients were administered the State Trait Anxiety Inventory for Children and the Children's Yale-Brown Obsessive Compulsive Scale. Serum toxoplasma IgG levels were determined from blood specimens collected from the study and control groups. The results were then compared using statistical methods. RESULTS: State and trait anxiety levels were significantly higher in the OCD and GAD patients than in the control group (p = .0001/.0001). Serum toxoplasma IgG levels were positive in 21 (35%) of the OCD patients, 19 (31.7%) of the GAD patients and 6 (10%) of the control group. A significant relation was determined between IgG positivity and GAD (p = .003). IgG-positive individuals were determined to have a 4.171-fold greater risk of GAD compared to those without positivity (4.171[1.529-11.378]) (p = .005). A significant relation was also determined between IgG positivity and OCD (p = .001). IgG-positive individuals were determined to have a 4.846-fold greater risk of OCD compared to those without positivity (4.846[1.789-13.126]) (p = .002). CONCLUSION: This study shows that serum toxoplasma IgG positivity indicating previous toxoplasma infection increased the risk of GAD 4.171-fold and the risk of OCD 4.846-fold in children and adolescents. Further studies are now needed to investigate the relation between T. gondii infection and GAD/OCD and to determine the pathophysiology involved. PMID- 28990852 TI - Using a situation awareness approach to determine decision-making behaviour in squash. AB - Situation awareness (SA) refers to the awareness of all relevant sources of information, an ability to synthesise this information using domain knowledge gained from past experiences and the ability to physically respond to a situation. Expert-novice differences have been widely reported in decision-making in complex situations although determining the small differences in expert behaviour are more elusive. This study considered how expert squash players use SA to decide on what shot to play. Matches at the 2010 (n = 14) and 2011 (n = 27) Rowe British Grand Prix were recorded and processed using Tracker software. Shot type, ball location, players' positions on court and movement parameters between the time an opponent played a shot prior to the player's shot to the time of the opponent's following shot were captured 25 times per second. Six SA clusters were named to relate to the outcome of a shot ranging from a defensive shot played under pressure to create time to an attempted winner played under no pressure with the opponent out of position. This new methodology found fine-grained SA differences in expert behaviour, even for the same shot type played from the same court area, beyond the usual expert-novice differences. PMID- 28990853 TI - Response to "Letter to the editor on the paper: The majority of natalizumab treated MS patients have high natalizumab concentrations at time of re-dosing". PMID- 28990854 TI - Impact of membrane partitioning on the spatial structure of an S-type cobra cytotoxin. AB - Cobra cytotoxins (CTs) belong to the three-fingered protein family. They are classified into S- and P-types, the latter exhibiting higher membrane-perturbing capacity. In this work, we investigated the interaction of CTs with phospholipid bilayers, using coarse-grained (CG) and full-atom (FA) molecular dynamics (MD). The object of this work is a CT of an S-type, cytotoxin I (CT1) from N.oxiana venom. Its spatial structure in aqueous solution and in the micelles of dodecylphosphocholine (DPC) were determined by 1H-NMR spectroscopy. Then, via CG- and FA MD-computations, we evaluated partitioning of CT1 molecule into palmitoyloleoylphosphatidylcholine (POPC) membrane, using the toxin spatial models, obtained either in aqueous solution, or detergent micelle. The latter model exhibits minimal structural changes upon partitioning into the membrane, while the former deviates from the starting conformation, loosing the tightly bound water molecule in the loop-2. These data show that the structural changes elicited by CT1 molecule upon incorporation into DPC micelle take place likely in the lipid membrane, although the mode of the interaction of this toxin with DPC micelle (with the tips of the all three loops) is different from its mode in POPC membrane (primarily with the tip of the loop-1 and both the tips of the loop-1 and loop-2). PMID- 28990855 TI - Alcohol Use and Frailty Risk among Older Adults over 12 Years: The Health and Retirement Study. AB - OBJECTIVES: The primary goal was to examine the relationship between alcohol use and frailty, a variable characterizing late-life decline, in a national, longitudinal survey of older adults living in the United States. METHODS: The sample drawn from the Health and Retirement Study included 9,499 stroke-free participants over age 65 in 2000. The sample was 59.1% female, and had a mean age of 74.25 years (SD = 6.99). Follow-up data was from 2004, 2008, and 2012. Frailty was defined phenotypically using the Paulson-Lichtenberg Frailty Index (PLFI). Alcohol use was measured via self-report. Control variables included age, race, education, socio-economic status (SES), depressive symptomatology, medical burden score, body mass index (BMI), and partner status. With abstinent participants as the reference group, logistic regressions were conducted to determine prevalent frailty at 2000, and Cox's proportional hazard models were utilized to determine time to incident frailty over a 12-year period. RESULTS: Results revealed that age, depressive symptomatology, and medical burden score were significant positive correlates of prevalent and incident frailty (p < .05) for both males and females. Logistic regressions revealed that consumption of 1-7 alcoholic drinks per week was associated with reduced prevalent frailty (OR = .49, p < .001) for females. Survival analysis results reveal that compared with nondrinkers, males and females who reportedly consumed 1-7 drinks per week had a decreased probability of incident frailty (HR = .78-081, p < .05). CONCLUSIONS: Findings suggest that moderate alcohol use confers reduced frailty risk for both older men and women. Future research should examine the mechanism(s) relating alcohol consumption and frailty. CLINICAL IMPLICATIONS: Findings support extant literature suggesting some healthcare benefits may be associated with moderate drinking. PMID- 28990857 TI - The role of regional heterogeneity in age-related differences in functional hemispheric asymmetry: an fMRI study. AB - Neuroimaging literature has documented age-related hemispheric asymmetry reduction in frontal regions during task performances. As most studies employed working memory paradigms, it is therefore less clear if this pattern of neural reorganization is constrained by working memory processes or it would also emerge in other cognitive domains which are predominantly lateralized. Using blocked functional magnetic resonance imaging (fMRI), the present study used a homophone judgment task and a line judgment task to investigate age-related differences in functional hemispheric asymmetry in language and visuospatial processing respectively. Young and older adults achieved similar task accuracy although older adults required a significantly longer time. Age-related functional hemispheric asymmetry reduction was found only in dorsal inferior frontal gyrus and was associated with better performance when the homophone condition was contrasted against fixation, and not line condition. Our data thus highlights the importance of considering regional heterogeneity of aging effects together with general age-related cognitive processes. PMID- 28990856 TI - Gaining insight into plant gene transcription using smFISH. AB - Single molecule RNA fluorescent in situ hybridization (smFISH) enables gene transcription to be assessed at the cellular level. In this point of view article, we describe our recent smFISH research in the model plant Arabidopsis thaliana and discuss how this technique could further knowledge of plant gene transcription in the future. PMID- 28990858 TI - Quantitative Analysis Of User Interfaces For Large Electronic Home Appliances And Mobile Devices Based On Lifestyle Categorization Of Older Users. AB - : Background/Study Context: The increasing longevity and health of older users as well as aging populations has created the need to develop senior-oriented product interfaces. This study aims to find user interface (UI) priorities according to older user groups based on their lifestyle and develop quality of UI (QUI) models for large electronic home appliances and mobile products. METHODS: A segmentation table designed to show how older users can be categorized was created through a review of the literature to survey 252 subjects with a questionnaire. Factor analysis was performed to extract six preliminary lifestyle factors, which were then used for subsequent cluster analysis. The analysis resulted in four groups. Cross-analysis was carried out to investigate which characteristics were included in the groups. Analysis of variance was then applied to investigate the differences in the UI priorities among the user groups for various electronic devices. Finally, QUI models were developed and applied to those electronic devices. RESULTS: Differences in UI priorities were found according to the four lifestyles ("money-oriented," "innovation-oriented," "stability- and simplicity oriented," and "innovation- and intellectual-oriented"). Twelve QUI models were developed for four different lifestyle groups associated with different products. Three washers and three smartphones were used as an example for testing the QUI models. CONCLUSION: The UI differences of the older user groups by the segmentation in this study using several key (i.e., demographic, socioeconomic, and physical-cognitive) variables are distinct from earlier studies made by a single variable. The differences in responses clearly indicate the benefits of integrating various factors of older users, rather than single variable, in order to design and develop more innovative and better consumer products in the future. The results of this study showed that older users with a potentially high buying power in the future are likely to have higher satisfaction when selecting products customized for their lifestyle. Designers could also use the results of UI evaluation for older users based on their lifestyle before developing products through QUI modeling. This approach would save time and costs. PMID- 28990859 TI - Hematoxylin Bodies in Pediatric Bone Marrow Aspirates and their Utility in the Diagnosis of Systemic Lupus Erythematosus. AB - In our recent case report, the finding of lupus erythematosus (LE) cells in a bone marrow aspirate led to the diagnosis of systemic lupus erythematosus (SLE) and appropriate treatment, although the patient was not clinically suspected to have SLE. To determine whether LE cells are present in the bone marrow aspirates of SLE patients, but overlooked in routine bone marrow morphology review, bone marrow aspirates from 30 pediatric patients (15 with SLE and 15 with other diagnoses) evaluated by rheumatologists were reviewed. LE cells were found in the bone marrow aspirates of only 1 SLE patient and none in non-SLE patients. However, hematoxylin bodies were identified in 53% (8/15) of SLE patients. Neither hematoxylin bodies nor LE cells were found in the aspirates from patients with other disorders. Three additional pediatric patients identified prospectively were found to have hematoxylin bodies in the bone marrow aspirates. Although the diagnosis was not initially suspected, 2 of the 3 patients were subsequently diagnosed with SLE. All patients with hematoxylin bodies and SLE had antinuclear antibody titers >=1:640 with a homogeneous staining pattern. In addition, bone marrow aspirates of 9 adult patients were reviewed, and neither LE cells nor hematoxylin bodies were identified. In summary, hematoxylin bodies were present in the bone marrow aspirates of many pediatric SLE patients, while LE cells were rare. The finding of hematoxylin bodies in pediatric bone marrow aspirates is a helpful and specific diagnostic clue that may lead to the diagnosis of SLE when other clinical features are nonspecific. PMID- 28990861 TI - Qualitative vs quantitative conceptions of homogeneity in nineteenth century dimensional analysis. AB - The emergence of dimensional analysis in the early nineteenth century involved a redefinition of the pre-existing concepts of homogeneity and dimensions, which entailed a shift from a qualitative to a quantitative conception of these notions. Prior to the nineteenth century, these concepts had been used as criteria to assess the soundness of operations and relations between geometrical quantities. Notably, the terms in such relations were required to be homogeneous, which meant that they needed to have the same geometrical dimensions. The latter reflected the nature of the quantities in question, such as volume vs area. As natural philosophy came to encompass non-geometrical quantities, the need arose to generalize the concept of homogeneity. In 1822, Jean Baptiste Fourier consequently redefined it to be the condition an equation must satisfy in order to remain valid under a change of units, and the 'dimension' correspondingly became the power of a conversion factor. When these innovations eventually found an echo in France and Great Britain, in the second half of the century, tensions arose between the former, qualitative understanding of dimensions as reflecting the nature of physical quantities, and the new, quantitative conception based on unit conversion and measurement. The emergence of dimensional analysis thus provides a case study of how existing rules and concepts can find themselves redefined in the context of wider conceptual changes; in the present case this redefinition involved a generalization, but also a shift in meaning which led to conceptual tensions. PMID- 28990860 TI - In a Genomic Era, Placental Pathology Still Holds the Key in the Nondysmorphic Stillbirth. AB - Objective To explore the relative utility of genetic testing in contrast to placental pathology in explaining causation of death in the structurally normal stillborn population. Methods A retrospective review of a structurally normal stillborn infant cohort in South East Scotland between 2011 and 2015, defined by death at or after 24 weeks of gestation. We reviewed pathology reports and collected demographic data on cases. This information was collated with genetic test results (quantitative fluorescent polymerase chain reaction and microarray analysis) and placental pathology to create a database for analysis. Primary Results Within the structurally normal population (n = 131), there were 125 genetic tests performed and 11 abnormal results. Sixty-six microarray analyses were performed, and 2 (3%) of the results were thought likely to reflect cause of stillbirth (1 case of incomplete trisomy 4 and 1 case of deletion of chromosome Xp in a female). Analysis was significantly limited in 2 cases as parental samples were not available. The placental pathology was available in a total of 129 cases; significant findings were identified in 100 cases; 79 (61%) showed changes that were considered to have caused death (including cord "accidents"), and a further 21 (16%) showed findings likely to influence the management of subsequent pregnancies. Conclusions We reaffirm the utility of placental examination in the investigation of stillbirth. In cases of nondysmorphic stillbirth where placental pathology does not explain the cause of stillbirth, microarray analysis of fetal DNA can add further diagnostic information in 3% of cases but can add further diagnostic confusion, and it is important that parental bloods are taken to minimize this risk. PMID- 28990862 TI - Sleep and Caregiving Experiences among Caregivers of Veterans in an Adult Day Health Care Program: A Pilot Study. AB - OBJECTIVES: This pilot study explored caregivers' attitudes toward core elements of a behavioral sleep intervention for managing sleep problems of older veteran care recipients and the caregivers, as an initial step for developing a dyadic sleep intervention program. METHODS: Five caregivers (all women; age range, 66-75 years) participated in a focus group discussion. Data were collected at one Veterans Affairs, adult day health care program. RESULTS: Caregivers' poor sleep was not necessarily explained by their caregiving responsibility. Caregivers felt that behavioral recommendations regarding sleep compression scheduling, increased indoor physical activity, and outdoor light exposure would be acceptable sleep interventions for themselves and the care recipients. Some challenges to the sleep recommendation were identified and they included limiting naptime of care recipients and change of their current sleep schedule. CONCLUSIONS: Caregivers are receptive to some key components of behavioral approaches to improving sleep. Tailored sleep recommendation strategy is needed to address potential challenges. CLINICAL IMPLICATIONS: If available within clinical care settings or delivered at the patient's home, caregivers of older veterans are likely to engage in behavioral sleep intervention programs. PMID- 28990863 TI - When Doctors Struggle: Current Stressors and Evaluation Recommendations for Physicians Contemplating Suicide. AB - The objective of this study was to document current risk factors associated with physicians' suicide ideation among a group of doctors enrolled in a Physician Health Program. A retrospective cohort study was drawn from administrative data. The study compared intake information between doctors who reported recent thoughts of suicide (n = 70) and those who did not (n = 1,572) using adjusted regression analysis. Current stressors included personal, financial, health, and occupational problems; ideation was more likely with multiple stressors. Physicians endorsing suicidal ideation lacked personal supports and scored differently on Short Form-36 measures. Evaluators treating physicians should assess enduring risks and current stressors, particularly multiple stressors, to help detect suicidal patients. Current stressors should not be viewed as transitory and it is critical to bring in collateral information. PMID- 28990864 TI - A frosty disagreement: John Tyndall, James David Forbes, and the early formation of the X-Club. AB - How do glaciers move? This seemingly straightforward question provided the backdrop for a heated debate between the physicists John Tyndall (1820-1893) and James David Forbes (1809-1868) in the late 1850s and early 1860s. Forbes described the motion of glaciers as that of a viscous fluid. After visiting the Alps, Tyndall proposed an alternative theory that combined fracture and regelation. The glacial controversy ensued. Yet the debate was never simply about whether glaciers moved like honey, or if they moved by continuously breaking and re-attaching. This paper shows that the glacial controversy formed an important prelude to the strategies used by the X-Club in reforming science and establishing cultural authority. There was a central difference in the way Forbes and Tyndall presented their scientific arguments. Tyndall and his allies used the changes in the periodical press as part of their strategy for establishing and maintaining cultural and scientific authority. By contrast, Forbes and his supporters, including the North British physicists, were not as quick to make use of this new medium. This paper, therefore, examines in detail the significance of these two publishing strategies in shaping the nature and results of the glacial controversy. PMID- 28990865 TI - Effects of physical randomness training on virtual and laboratory golf putting performance in novices. AB - External randomness exists in all sports but is perhaps most obvious in golf putting where robotic putters sink only 80% of 5 m putts due to unpredictable ball-green dynamics. The purpose of this study was to test whether physical randomness training can improve putting performance in novices. A virtual random physics golf-putting game was developed based on controlled ball-roll data. Thirty-two subjects were assigned a unique randomness gain (RG) ranging from 0.1 to 2.0-times real-world randomness. Putter face kinematics were measured in 5 m laboratory putts before and after five days of virtual training. Performance was quantified using putt success rate and "miss-adjustment correlation" (MAC), the correlation between left-right miss magnitude and subsequent right-left kinematic adjustments. Results showed no RG-success correlation (r = -0.066, p = 0.719) but mildly stronger correlations with MAC for face angle (r = -0.168, p = 0.358) and clubhead path (r = -0.302, p = 0.093). The strongest RG-MAC correlation was observed during virtual training (r = -0.692, p < 0.001). These results suggest that subjects quickly adapt to physical randomness in virtual training, and also that this learning may weakly transfer to real golf putting kinematics. Adaptation to external physical randomness during virtual training may therefore help golfers adapt to external randomness in real-world environments. PMID- 28990866 TI - Neuroanatomical correlates of emotion-processing in children with unilateral brain lesion: A preliminary study of limbic system organization. AB - In this study, MRI and DTI were employed to examine subcortical volume and microstructural properties (FA, MD) of the limbic network, and their relationships with affect discrimination in 13 FL (6 right FL, M = 10.17 years; 7 left FL; M = 10.09) and 13 typically-developing children (TD; M = 10.16). Subcortical volume of the amygdala, hippocampus and thalamus and FA and MD of the fornix and anterior thalamic radiation (ATR) were examined. Results revealed no group differences across emotion-perception tasks or amygdalar volume. However, contrasting neuroanatomical patterns were observed in right versus left FL youth. Right FL participants showed increased left hippocampal and thalamic volume relative to left FL participants; whereas, the latter group showed increased right thalamic volume. DTI findings also indicated right FL children show greater MD of right fornix than other groups, whereas, left FL youth showed greater MD of left fornix. Right FL youth also showed lower FA of right fornix than left FL children, whereby the latter showed greater FA of left fornix and ATR. Differential associations between DTI indices and auditory/visual emotion perception were observed across FL groups. Findings indicate diverging brain behavioral relationships for emotion-perception among right and left FL children. PMID- 28990868 TI - Prevention of recognition memory loss and moderation of mitochondrial dynamic tendency toward fusion by flavone derivatives in Abeta-injected rats: a comparison between two flavonoids with different polarity. AB - Growing evidence sheds light on the use of flavonoids as the promising alternatives for the treatment of chronic conditions, including cancer and neurodegenerative disorders. Accordingly, in the present study, we aimed at evaluating the effects of oral intake of two structurally different flavonoids 5 hydroxy-6,7,4'-trimethoxyflavone (flavone 1) and 5,7,4'-trihydroxyflavone (flavone 2) on recognition memory, hippocampal protein level of immediate early gene cFos and mitochondrial dynamic markers in Amyloid beta (Abeta)-injected rats. Recognition aspect of memory and level of proteins were measured using novel object recognition test and Western blot, respectively. Our data indicated that even though flavone 1 was more effective than flavone 2 to prevent memory impairment, feeding with both flavones alleviated memory in Abeta-injected rats. Furthermore, in flavones-administered rats, mitochondrial dynamic balancing returned to the control level by the decline in Dynamin-related protein-1 protein level, a known marker for mitochondrial fission, and elevation in protein level of mitochondrial fusion factors Mitofusins 1 and 2. In parallel with behavior results, flavone 1 was more effectual on mitochondrial dynamic moderating. The more neuroprotective effects of flavone 1 could be attributed to its methylated structure leading to crossing of the blood-brain barrier with ease and metabolic stability and bioactivity. PMID- 28990867 TI - Characterization of colchicine binding with normal and glycated albumin: In vitro and molecular docking analysis. AB - The transport of more than 90% of the drugs viz. anticoagulants, analgesics, and general anesthetics in the blood takes place by albumin. Hence, albumin is the prime protein needs to be investigated to find out the nature of drug binding. Serum albumin molecules are prone to glycation at elevated blood glucose levels as observed in diabetics. In this piece of work, glycation of bovine serum albumin (BSA) was carried out with glyceraldehyde and characterized by molecular docking and fluorometry techniques. Glycation of BSA showed 25% loss of free amino groups and decreased protein fluorescence (60%) with blue shift of 6 nm. The present study was also designed to evaluate the binding of colchicine (an anti-inflammatory drug) to native and glycated BSA and its ability to displace 8 analino-1-nephthalene sulfonic acid (ANS), from the BSA-ANS complex. Binding of ANS to BSA showed strong binding (Ka = 4.4 MUM) with native conformation in comparison to glycated state (Ka = 8.4 MUM). On the other hand, colchicine was able to quench the fluorescence of native BSA better than glycated BSA and also showed weaker affinity (Ka = 23 MUM) for glycated albumin compared with native state (Ka = 16 MUM). Molecular docking study showed that both glyceraldehyde and colchicine bind to common residues located near Sudlow's site I that explain the lower binding of colchicine in the glycated BSA. Based on our results, we believe that reduced drugs-binding affinity to glycated albumin may lead to drugs accumulation and precipitation in diabetic patients. PMID- 28990869 TI - Similar results but not the same: because of the different ways. PMID- 28990870 TI - Response to Brand and McEwen (2016) Editorial: Advocacy for violations of legal rights is not advocacy for justice. PMID- 28990872 TI - A Comparison of the Influence of Anticipated Death Trajectory and Personal Values on End-of-Life Care Preferences: A Qualitative Analysis. AB - OBJECTIVES: We examined anticipated preferences for end-of-life (EOL) care in healthy older adults in the context of various terminal disease scenarios to explore the relationship between personal values and diseases and conditions that would influence EOL care choices. METHODS: Qualitative Descriptive Analysis was used to derive themes and the relationship between EOL preference themes and personal value themes in 365 respondents in a national sample of healthy older adults who completed a survey on their anticipated preferences for end-of-life (EOL) care. RESULTS: Reluctance to burden close others was the most frequently voiced personal value across all conditions affecting EOL preferences, followed by the personal value of quality of life. Concern about whether one's wishes would be honored was more commonly voiced in the context of hypothetical, prospective terminal cancer than in neurological conditions. Respondents who voiced desire for autonomy in how they would die clearly attributed extreme pain as the primary influence on EOL preferences. CONCLUSIONS: Comprehensive assessment of patient personal values should include consideration of particular chronic disease scenarios and death trajectories to fully inform EoL preferences. CLINICAL IMPLICATIONS: Because personal values do influence EOL preferences, care should be taken to ascertain patient values when presenting diagnoses, prognoses, and treatment options. In particular, patients and families of patients with progressive neurological diseases will likely face a time when the patient cannot self-represent EOL wishes. Early discussion of values and preferences, particularly in the context of cognitive disease is vital to assure patient directed care. PMID- 28990871 TI - Cultural Adaptation of a Dyadic Intervention for Korean Couples Coping with Alzheimer's Disease. AB - OBJECTIVES: The Couples Life Story Approach (CLSA) was recently developed in the U.S. for older couples dealing with dementia to improve their quality of life. The purpose of this article is to describe how the CLSA was adapted to be culturally appropriate for older Korean couples and to discuss cultural themes that emerged during the implementation process. METHODS: The intervention was adapted using the Cultural Adaptation Process Model. The revised materials were implemented on 56 Korean couples. A multiple case study method was used to analyze the clinical data. RESULTS: Four cultural themes were identified: (1) dealing with negative memories in early years of marriage; (2) communication styles and patterns; (3) ways to incorporate difficult life events into the Life Story Book; and (4) complex dynamics of heirarchy in the relationship between older couples and the interventionist. With each theme, case examples are described that illustrate relevant issues. CONCLUSIONS: Cultural adaptation can be conducted systematically to improve the delivery of the CLSA for different populations. CLINICAL IMPLICATIONS: Cliniocians working with older Korean couples affected by dementia should consider cultural uniqueness in a life-story approach. PMID- 28990873 TI - Third-line treatment with second-generation tyrosine kinase inhibitors (dasatinib or nilotinib) in patients with chronic myeloid leukemia after two prior TKIs: real-life data on a single center experience along with the review of the literature. AB - OBJECTIVES: Newer tyrosine kinase inhibitors (TKIs) (bosutinib, ponatinib) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) can be utilized as a salvage therapy in patients with chronic myeloid leukemia (CML) who failed two lines (imatinib -> nilotinib or imatinib -> dasatinib) of TKI therapy. However, these TKIs are not available in many countries and not all patients can undergo allo-HSCT. METHODS: In this study, CML patients who received dasatinib or nilotinib as a third-line treatment were retrospectively evaluated. RESULTS: Out of 209 patients, third-line dasatinib/nilotinib was administered in 21. During the follow-up, 16 out of 21 patients gained and/or maintained an optimal response, and 4 patients died due to progression. Seventeen patients were alive at the time of the analysis, of which 13 were still on TKI, whereas 4 patients quit treatment. DISCUSSION: In patients failing two lines of TKI, dasatinib or nilotinib can be beneficial and safely administered as a third-line treatment especially in nations with restricted resources. PMID- 28990874 TI - Intensive Gait Treatment Using a Robot Suit Hybrid Assistive Limb in Acute Spinal Cord Infarction: Report of Two Cases. AB - CONTEXT: Spinal cord infarction (SCI) causes gait disturbance because of paresis, spasticity, and sensory disturbance of the lower limbs. There is no effective medical treatment for SCI, and conventional rehabilitation alone is the main approach to helping individuals work toward independent walking. The aim of this study was to evaluate the effect of gait treatment using the Hybrid Assistive Limb (HAL) on acute SCI. FINDINGS: A 61-year-old female and a 62-year-old male with incomplete paraplegia participated in this study. Our study participants received gait treatment with HAL 3-4 times per week, with a total of 7-8 sessions (20 min), in addition to conventional physical therapy. The American Spinal Injury Association Impairment Scale, Lower Extremity Motor Score (LEMS), Modified Ashworth Scale (MAS), the Walking Index for Spinal Cord Injury (WISCI II), comfortable gait speed (CGS), stride, cadence, Barthel Index (BI), Functional Independence Measure (FIM), modified Rankin Scale (mRS), joint angles, and adverse effects were assessed prior to HAL treatment and post-HAL treatment. HAL facilitated intensive gait treatment in people during the acute phase after SCI. Improvements in LEMS, WISCI II, CGS, stride, cadence, BI, FIM, mRS, and joint angles were observed in both study participants. Furthermore, decreased spasticity in the gastrocnemius muscle was found in one participant as assessed by MAS. CONCLUSION: Gait treatment using HAL may be beneficial for paraplegic, non-ambulatory individuals with acute SCI. HAL may be useful for intensive gait treatment without increasing spasticity. PMID- 28990875 TI - Stress-buffering Effect of Coping Strategies on Interrole Conflict among Family Caregivers of People with Dementia. AB - OBJECTIVES: To examine the stress-buffering effect of coping strategies on the adverse effects of interrole conflict on the mental health of employed family caregivers, and clarify the moderating role of attentional control on this stress buffering effect. METHODS: Data were drawn from a two-wave longitudinal online survey of employed Japanese family caregivers of people with dementia (263 males, 116 females; age 51.54 +/- 9.07 years). We assessed interrole conflict, coping strategies, attentional control, mental health variables (psychological strain and quality of life), and confounding factors. RESULTS: Hierarchical regression analyses controlled for sociodemographic factors found formal support seeking had a stress-buffering effect for strain- and behavior-based caregiving interfering with work (CIW) only on psychological strain, and was moderated by attentional control. Single slope analysis showed higher CIW was related to higher psychological strain in those with greater use of formal support seeking and lower attentional control, but not in those with higher attentional control. CONCLUSIONS: Greater use of formal support seeking weakens the adverse effects of strain- and behavior-based CIW on psychological strain in people with high attentional control. CLINICAL IMPLICATIONS: Attentional control is a key factor in the stress-buffering effect of formal support seeking on strain- and behavior based CIW. PMID- 28990876 TI - Coming In: Queer Narratives of Sexual Self-Discovery. AB - Many models of queer sexuality continue to depict a linear narrative of sexual development, beginning in repression/concealment and eventuating in coming out. The present study sought to challenge this by engaging in a hermeneutically informed thematic analysis of interviews with eight queer people living in Western Australia. Four themes were identified: "searching for identity," "society, stigma, and self," "sexual self-discovery," and "coming in." Interviewees discussed internalized homophobia and its impact on their life; experiences and implications of finding a community and achieving a sense of belonging; the concept of sexual self-discovery being a lifelong process; and sexuality as fluid, dynamic, and situational rather than static. The article concludes by suggesting that the idea of "coming in"-arriving at a place of acceptance of one's sexuality, regardless of its fluidity or how it is viewed by society-offers considerable analytic leverage for understanding the journeys of sexual self-discovery of queer-identified people. PMID- 28990878 TI - Polyvictimization in later life: Trauma-informed best practices. AB - This article provides a summary of salient trauma findings and conveys the dearth of research pertaining specifically to the trauma of elder abuse. This material, in conjunction with information contained in other articles composing this special issue, lays the foundation for advancing a trauma-informed approach to assisting older adults who have experienced polyvictimization. Informed by the findings presented and their extensive clinical experience with victims of violence, the authors suggest steps for providing a trauma-informed and victim centered response to older adults who have suffered polyvictimization. These steps are then illustrated with an in-depth late-life polyvictimization case analysis. PMID- 28990877 TI - Parents' descriptions of young children's dissociative reactions after trauma. AB - There is limited research on the phenomenology of how young children who have been exposed to trauma express the intrusive symptom of dissociative reactions. The current qualitative study utilized interviews from a semi-structured diagnostic clinical interview with 74 caregivers of young children (ages 3 to 7) who were exposed to trauma to identify parents' descriptions of their children's dissociative reactions during a clinical interview. Based on results from the interview, 45.9% of the children had dissociative reactions (8.5% had flashbacks and 41.9% had dissociative episodes). Interviews were transcribed to identify themes of dissociative reactions in young children. Common themes to flashbacks and dissociative episodes included being triggered, being psychologically in their own world (e.g., spaced out and shut down), and displaying visible signs (e.g., crying and screaming). For flashbacks, caregivers reported that it seemed as if the child was re-experiencing the trauma (e.g., yelling specific words and having body responses). For dissociative episodes, caregivers noted that the child not only seemed psychologically somewhere else (e.g., distant and not there) but also would be physically positioned somewhere else (e.g., sitting and not responding). Caregivers also expressed their own reactions to the child's dissociative episode due to not understanding what was occurring, and trying to interrupt the occurrences (e.g., calling out to the child). Themes, descriptions, and phrases to describe dissociative reactions in young children after trauma can be used to help parents and professionals more accurately identify occurrences of dissociative reactions. PMID- 28990879 TI - Shaping LGBTQ Identities: Western Media Representations and LGBTQ People's Perceptions in Rural Spain. AB - A growing academic discussion has focused on how, in a globalized world, LGBTQ identities are shaped and influenced by different and international actors, such as the media. This article analyzes how LGBTQ people from a rural region of a Western country-Spain-feel toward their representations on TV series from English speaking countries. Employing a qualitative approach, this research aims to depict whether the academic conceptualizations to analyze these identity conformation processes are accurate. In addition, it explores how dominating media representations are being adapted in a region that, although within the West, can serve a context of a very different nature. The results found that a major rejection of the TV series representations among participants can suggest both an inaccuracy of the conceptualizations used by some scholars to understand LGBTQ flows and a problematic LGBTQ representation in media products that goes beyond regions and spaces. PMID- 28990880 TI - Older adults affected by polyvictimization: A review of early research. AB - In contrast to work within the child-abuse field, polyvictimization of older adults did not become a focus of professional attention until this decade. Despite this lack of formal identification, a search of the research and practice literature revealed that prior research investigating single forms of or other elder abuse issues contained evidence of what was variously termed "multiple," "multi-faceted," "co-occurring," or "hybrid" elder abuse. A wide range of victims (1.4%-89.7%) identified in existing elder abuse studies was found to have experienced what constitutes "polyvictimization." This late-life polyvictimization evidence, the contexts in which victims are harmed, and information regarding the impact of multifaceted elder abuse are all presented and discussed in this article. Selected published cases illustrate the clinical dynamics operating in late-life polyvictimization situations. PMID- 28990881 TI - Fear of Falling Restricts Activities of Daily Living after Total Hip Arthroplasty: A One-Year Longitudinal Study. AB - OBJECTIVES: To determine the prevalence and time course in changes regarding the fear of falling and whether there are consequent restrictions in activities of daily living (ADL) after total hip arthroplasty (THA). METHODS: This is 1-year longitudinal observational study. We recruited ninety-eight patients before and after THA. Fear of falling was assessed for 12 ADLs preoperatively and postoperatively at 3, 6, and 12 months following THA. In addition, we asked patients to answer whether they had refrained from performing each ADL because of fear of falling. RESULTS: Fifty-two patients were enrolled for the analysis. The total fear of falling score during ADLs decreased with time after THA. The ADLs in which many patients (over 20%) felt fear even at 12 months were using the stairs (25%), sitting and standing from the floor (23%), and walking around the neighborhood (21%). Approximately 10% of patients were restricted in performing ADLs, such as sitting and standing from the floor, because of fear. CONCLUSIONS: Patients undergoing THA frequently experience fear of falling during some ADLs even at 1 year after the operation, which could cause ADL restrictions. CLINICAL IMPLICATIONS: Clinicians should evaluate fear of falling and institute rehabilitation programs individually to decrease excessive fear that might lead to ADL restrictions. PMID- 28990882 TI - Sleep Schedule Regularity Is Associated with Sleep Duration in Older Australian Adults: Implications for Improving the Sleep Health and Wellbeing of Our Aging Population. AB - OBJECTIVES: The National Sleep Foundation (NSF) recommends 7 to 9 hours of sleep per night for adults >= 65 years of age. Sleep duration below 7h per night has been associated with negative health consequences, so enabling older adults to obtain at least 7 hours per night is important for health and wellbeing. However, little is known about behavioral factors that support sleep duration (>= 7h/24h) in this group. Our aim was to determine factors associated with sleep duration in older adults, and evaluate the utility of sleep schedule regularity in particular, given the relationship between lifestyle regularity (of which sleep is an important component) and health in this population. METHODS: A sample of 311 Australian adults (>= 65 years old; 156 male, 155 female) completed a telephone survey assessing sleep history over the prior 24 hours, sleep schedule regularity, demographic and health factors as part of a larger study of the Australian population. RESULTS: Sleep schedules with variability in bed and rise times of > 60 minutes were associated with increased odds of reporting sleep duration below 7 hours per night (< 7h/24h; OR = 2.38, CI = 1.26-4.48, p = .007). No other behaviors were associated with meeting sleep duration recommendations. CONCLUSIONS: Sleep schedule regularity may be associated with sleep duration (>= 7h/24h) in older adults. CLINICAL IMPLICATIONS: Empowering older adults to maintain sleep schedule regularity may be a practical and efficacious strategy to support sleep durations that are in line with recommendations (>= 7h/24h). PMID- 28990883 TI - Learning to address multiple syndemics for people living with HIV through client perspectives on CBT. AB - OBJECTIVE: The mental health burden among people living with HIV/AIDS (PLWHA) is high and often involves multiple comorbid psychological and substance use-related psychosocial problems. These co-occurring problems, or syndemics, additively impair engagement in HIV disease management. Existing psychotherapies for mental health and HIV health have generally focused on a single psychosocial problem and little research exists to guide future psychotherapies that address multiple mental health issues. METHOD: To address this gap in understanding, we conducted qualitative interviews with multiply comorbid PLWHA (N = 30) who completed cognitive-behavioural therapy (CBT) for depression and medication adherence. RESULTS: Themes emerged regarding participants' perspectives on how overlapping substance use and mood disorders interacted to reduce the benefit of CBT. Substance use was a dominant theme compared to other syndemics, highlighting the need for integrated mental health and substance use interventions. Interviews also suggested modifications of which psychosocial concerns participants felt should be prioritized in treatment delivery. Finally, participants described content they would want in a psychotherapy intervention, including intimacy and sexual health. CONCLUSIONS: Future psychotherapeutic interventions for syndemic problems and HIV self-care will need to comprehensively address complex concerns, including issues salient to the overall well-being of PLWHA. This may improve client engagement and, ultimately, mental, and physical health outcomes. PMID- 28990885 TI - Evaluation and importance of different types of inhaler device in patients with chronic obstructive lung disease. AB - Introduction: Inhaled medications are used in chronic airway disease including chronic obstructive pulmonary disease (COPD) and give the opportunity of low doses, lower side effects, and fast effectiveness. Inhaler devices are frequently used incorrectly by patients. Today, it is generally accepted that poor device use is one of the reasons for poor disease control and low adherence. The aim of the study was to investigate a sample of patients with COPD prescribed with inhaled medication and to evaluate the frequency and pattern of incorrect inhaler use as well as affecting factors. Materials and Methods: One hundred and eighty consecutive patients who attended the outpatient clinic with the diagnosis of COPD and were prescribed and receiving different types of inhaler drugs at least for one month were included. The patient's ability to use the devices according to steps was scored face to face after they had replied a questionnaire consisting of 26 questions about their inhaler training and disease specifications. The parameters that may affect incorrect use, pattern of incorrect use, characteristics of the patients who experienced incorrect use, and impact of training were evaluated. Chi-Square and Fisher's Exact test were used for statistical analysis. Result: The rate of correct use including all steps was 26.3% for metered-dose inhaler (pressurized MDI), 30.4% for inhalation capsule aerolizer, 40.5% for diskus, and 46.3% for turbuhaler. The parameters affecting correct use and number of critical errors causing insufficient drug inhalation were type and duration of initial training due to inhaler devices and also duration and stage of the disease. Conclusions: COPD patients who were prescribed an inhaler drug should be regularly checked and re-trained during out-patient visits on how to use the inhaler device correctly step by step. PMID- 28990886 TI - [Assessing the knowledge in primary health care following an educational course structured in the context of GARD chronic airway diseases national control program]. AB - Introduction: Chronic obstructive pulmonary diseases are common causes of disease in the community and account for considerable percent of the caseload in primary health care facilities. For this reason, it is important to question and improve the knowledge of primary health care physicians. This study is designed to assess the level of knowledge for bronchial asthma and COPD of the primary healthcare physicians, both before and immediately after an educational course structured in the context of GARD Chronic Airway Diseases National Control Program. Materials and Methods: The participating physicians attended an intensive educational course on asthma and COPD. Twenty five item questionnaires for asthma and COPD were administered to the participants both before and immediately after the end of the course. Contribution of education to the level of knowledge was investigated by comparing the percentages of the correct answers in the pre-and post-test. Result: From 11 different cities, 1817 and 1788 primary health care physician were attended to the asthma and COPD educations, respectively. The accuracy rate of >= 75% was obtained from only 4 questions in pre-test asthma questionnaire. On the contrary, in 15 questions the accuracy rate was < 50%. The mean accuracy rate for the whole asthma test was 45.8%, and this rate raised to 69.6% after education course. The accuracy rate of >= 75% could not be obtained from any of the questions in pre-test COPD questionnaire. On the contrary, in 19 questions the accuracy rate was < 50%. The mean accuracy rate for the whole asthma test was 42.0%, and this rate raised to 71.3% after education course. Conclusions: It has been shown that, in primary care settings, the level of knowledge in asthma and COPD should be enhanced and that this increase can be achieved with an education course. PMID- 28990884 TI - Psychosocial Predictors of Anxiety in Nursing Home Staff. AB - OBJECTIVES: Although research shows that nursing home staff experience significant levels of stress and burnout, studies analyzing the relationship of psychosocial variables on their feelings of anxiety are scarce. This study aims to analyze the relationship between psychosocial variables and levels of anxiety among staff. METHOD: Participants were 101 nursing home professionals. In addition to anxiety, socio-demographic variables, depersonalization, burden, relationship with families of the residents, and guilt about the care offered to the residents were assessed. A hierarchical regression analysis was carried out to analyze the contribution of the assessed variables to staff anxiety levels. RESULTS: The obtained model explained 57% of the variance in anxious symptomatology. Guilt about the care offered and poor quality of the relationship with residents' family were associated with anxiety. Further, working at nursing homes where the staff report higher levels of anxiety symptoms, the presence of depersonalization and burden were also associated with anxiety. CONCLUSION: The findings suggest that in addition to work-related variables (burden and burnout), problems with family members and guilt about the care offered are relevant variables for understanding staff's anxious symptomatology. CLINICAL IMPLICATIONS: Interventions that address issues of guilt about the quality of care, and problematic relationships with family members of residents, may have potential to reduce staff anxiety and promote their well-being. PMID- 28990887 TI - IL-1beta polymorphism in COPD patients in Turkish population. AB - Introduction: Chronic obstructive pulmonary disease (COPD) is a common respiratory condition characterized by persistent airflow limitation and is associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases. Interleukin-1 beta (IL-1beta) is a major pro inflammatory cytokine expressed by many cells such as macrophages, neutrophils and monocytes and functions in cellular activities such as proliferation, differentiation and apoptosis. Recent studies demonstrate controversial results about the relationship between IL-1beta and COPD. The aim of this study is to investigate the association between IL-1beta -511 (rs 16944) and +3954 (rs 1143634) gene polymorphisms and COPD in Turkish population. Materials and Methods: A total of 152 subjects were recruited in the study and divided into three groups: 72 COPD patients, 41 healthy smokers and 39 never-smokers. PCR-RFLP method was used to determine the allele frequencies, genotype and haplotype distributions. Result: We did not find any significant difference between the gene polymorphisms and COPD by means of genotype frequencies, haplotype association, stage, gender or smoking status (p< 0.05). Conclusions: Our results do not show any evidence of association between COPD and IL-1beta -511 and +3954 gene polymorphisms in Turkish population. PMID- 28990889 TI - [Role of quantitative perfusion scintigraphy evaluation in determination of the efficiency of the procedure before lung volume reduction coil treatment for severe emphysema]. AB - Introduction: Lung volume reduction coil (LVRC) is a new treatment method which exercise capacities among the patients with severe emphysema. In order to determine the emphysema distribution before LVRC treatment, we examined the contribution of combination of the high resolution computed tomography (HRCT) of the lung and the quantitative perfusion scintigraphy to the efficiency of the procedure. Materials and Methods: The study was conducted retrospectively. The densitometry analysis and scores of emphysema areas of the patients who were found suitable for LVRC treatment in HRCT were determined. Before the procedure, the quantitative lung perfusion scintigraphies were taken. Lobes which had high emphysema score and in which a decrease perfusion was observed in quantitative perfusion scintigraphy were determined as treatment areas. Result: A total of 22 patients were treated. In HRCT it was observed that perfusion decreased in lobes in which the emphysema damage scoring was high. A significant statistical difference was found between pre-and post- procedure measurements in terms of FEV1, RV, and TLC (p<0.05). In six minute walk test, a statistically significant difference was found as 45.4 +/- 23.9 m (p= 0.000). No significant difference was determined between perfusion ratios before the procedure and perfusion ratios after the procedure. Conclusions: The quantitative perfusion scintigraphy taken before LVRC treatment in severe emphysema patients guides to determine the target lobe for treatment and makes contribution to the efficiency of the procedure. PMID- 28990888 TI - [Lung carcinoma patients aged eighty years over and prognostic factors affecting survival]. AB - Introduction: Almost 50% of all cancers and 70% of cancer deaths occur in cases aged 65 years and more. Thus diagnosis, treatment and follow up in old cases gain importance. Since there a limited number of study that show age-mortality relation in lung cancer cases aged 80 years and over, issues may arise in diagnosis and treatment process of these cases. In this study, we aimed to evaluate general characteristics of lung cancer cases aged 80 years or over and factors that affect survey. Materials and Methods: Between 2010 and 2013, the retrospective cohort study was done in Sureyyapasa Chest Diseases and Chest Surgery Training and Research Hospital and 100 cases of lung carcinoma were examined. Result: In the study, 70% of the cases were male and 30% were female. Median age was 83 +/- 2.91 (80-92) years. 71% of the cases were found to be suffering from a comorbid disease; 29% did not have any comorbid disease. Dyspnea (56%), cough (50%) and chest pain (41%) were the most frequent symptoms. Histopathologically, 41% of the patients diagnosed with adenocarcinoma and 40% were diagnosed with squamous cell carcinoma. Median survival time was 2.73 months (%95 CI 0.96-4.49) and 1-year survival rate was 17%. Length of time of the cases with smoking history was found shorter than of cases without smoking history (p= 0.013). Life expectancy of the cases with advanced disease and performance score of 3-4 was detected to be short (p= 0.006, p< 0.001). Compared to the cases who operated on and had chemoradiotherapy, length of life who had symptomatic treatment was shorter (p< 0.001). Conclusions: Despite the comorbidity in lung cancer cases aged 80 years and over, life expectancy of the cases who had surgical and/or chemoradiotherapy treatment is longer. While deciding on treatment methods on these cases, patient's performance must be taken into consideration. PMID- 28990890 TI - Effect of reduction mammoplasty on the pulmonary function tests. AB - Introduction: Bilateral breast reduction surgery is the surgical treatment of bilateral breast hypertrophy. This is one of the most common breast surgery requested by women, and performed by plastic surgeons. The reasons that patients want this surgery are to re-size sagging breasts aesthetically, and to get rid of somatic symptoms such as shoulder, chest, back, and neck pain. We believe that the objective positive effects of breast reduction surgery exist beside aesthetic. In our study, our aim is to elicit positive effects of surgery on lungs, if there are, by making pulmonary function test and carbon monoxide diffusion test before surgery and after 6 months of surgery. Materials and Methods: Thirty patients agreed to participate in the study. Study is completed with 19 patients. Pulmonary function test and carbon monoxide diffusion test were made to all patients in preoperative and 6 months of postoperative period. Lung roentgenogram of all patients was performed and height, weight, body mass index were measured. Saturation level was measured. Result: There was a meaningful increase in FEV1 and FVC values in the postoperative period in comparison with pulmonary function test performed in preoperative period. DLCO in postoperative period decreased meaningfully as compared to the preoperative period. Conclusions: Breast reduction surgery seems to have positive effects on pulmonary function test values and relaxes patients clinically. Patients with big breasts should be evaluated from this perspective if they apply chest diseases clinic with shortness of breath. PMID- 28990891 TI - [Turkish Thoracic Society national spirometry and laboratory standards]. AB - The application quality of pulmonary function tests (PFT) carries high importance since it affects the quality of health services. "Chronic Diseases and Risk Factors in Turkey Study," which was published in 2013 showed that only 22.6% of PFTs performed in the secondary care institutions in our country were compatible with the standards. This finding reveals the standardization problem in spirometry applications in our country. Currently, the criteria for the application and evaluation of spirometer measurements were defined by American and European Respiratory Societies standards. Several laboratories use these standards in our country as in the world. But, national laboratory standards that are suitable for the conditions in our country have not been defined yet. This report was prepared to ensure the application of spirometry in optimal conditions, to minimize intra-laboratory and inter-laboratory differences and mistakes, and to standardize in our country. In this report, we focused on the standards concerning laboratory conditions, equipment, and technician specifications, test application, evaluation of test quality, infection control, and reference values. PMID- 28990892 TI - Hepatitis C and pulmonary fibrosis. AB - Hepatitis C is one of the most important infectious agents worldwide. There are conflicting results regarding the relationship between pulmonary fibrosis and hepatitis C. It is thought that hepatitis C may play a role in the development or exacerbations of idiopathic pulmonary fibrosis, but no clear link between hepatitis C and pulmonary fibrosis development has been demonstrated yet to date. In the recent era, indirect effects of hepatitis C rather than a direct effect are more suspected on pulmonary fibrosis. These indirect effects could also been documented only by a few case-based studies. PMID- 28990893 TI - [Pollen food allergy syndrome]. AB - Pollen food allergy syndrome, is a type I cross-reaction mediated by IgE antibodies between an aeroallergen and a plant-derived antigen. Main symptoms are typically consist of localized oral symptoms such as numbness of the lip or mouth, itching, tingling and swelling of lips, tongue, palate and pharynx without systemic symptoms. Patients with seasonal allergic rhinitis, asthma or both more frequently experience pollen food allergy syndrome. Because most patients have mild symptoms and the improvement by avoiding food, the true incidence is unknown. In this review, we aimed to discuss characteristics, diagnosis and treatment of pollen food allergy syndrome according to existing literature. PMID- 28990894 TI - Red flag; wheezing with neck pain may be a clue to the early diagnosis of spontaneous pneumomediastinum. AB - Spontaneous pneumomediastinum is an uncommon clinical condition in pediatric field. We report two pediatric cases with first time wheezing episode complicated by pneumomediastinum. Investigations failed to reveal any underlying cause for secondary pneumomediastinum. Pneumomediastinum most commonly occurs in asthmatic children. It can be explained by increased pressure gradient between the intraalveolar and interstitial spaces. We conclude that high prevalence of respiratory infections in children predisposes for spontaneous pneumomediastinum due to increased pressure within obstructed airways, or by tissue necrosis from parenchymal infection. PMID- 28990895 TI - A rare synchronous tumor: primary squamous cell lung cancer and adenoid cystic carcinoma of the tongue. AB - Persence of multipl primary tumors in an organism is called as multiple primary cancer (MPC). Multipl tumors that occur at the same time are synchronized tumors, while those occuring at the different times called metachronous. MPCs are very rare entities. Here in we report a 96-year-old man who presented with synchronous MPC including squamous cell Lung cancer and tongue adenoid cystic carcinoma. PMID- 28990896 TI - Acute eosinophilic pneumonia secondary to heroin inhalation. AB - Smoking heroin (chasing the dragon), is a method of inhaling heroin via heating the drug on a tin-foil above a flame. It also has been associated both with the indirect effects of heroin overdose and with direct pulmonary toxicity. We describe a case of acute eosinophilic pneumonia secondary to heroin inhalation in our medical intensive care unit. She presented with fever, cough, dyspnea and pleuritic chest pain. Chest radiograph showed bilateral infiltrations. Examination of bronchoalveolar lavage fluid revealed significant eosinophilia. She was diagnosed with acute eosinophilic pneumonia. After heroin abstinence and corticosteroid therapy, remission was achieved rapidly and the patient was discharge on the fourth day of her hospital stay. PMID- 28990897 TI - Chronic necrotizing pulmonary aspergillosis in an immunocompetent patient after the surgery of hydatid cyst. AB - Chronic necrotizing pulmonary aspergillosis (CNPA) is a condition caused by the ubiquitous fungus Aspergillus fumigatus in non-immunocompromised individuals. Numerous underlying conditions have been associated with CNPA. Tuberculosis, non tuberculous mycobacterial infection and allergic bronchopulmonary aspergillosis (ABPA) remain the predominant risk factors for development of CNPA. Development of CNPA in echinococcal cyst cavities is very rare and the optimal therapeutic regimen and treatment duration have not been established. Here, we present a case of CNPA developed six years after the cystectomy operation of hydatid cyst and treated with voriconazole successfully. PMID- 28990898 TI - Lipoma adjacent to scapula in an elderly. PMID- 28990899 TI - Cytomegalovirus pneumonia in an immunosuppressed child mimicking interstitial lung disease. PMID- 28990900 TI - Duodenal and pancreas metastasis from lung cancer. PMID- 28990901 TI - Corrigendum: Association of codon 72 polymorphism of p53 with the severity of cervical dysplasia, E6-T350G and HPV16 variant lineages in HPV16-infected women. PMID- 28990902 TI - Advocating for the Fogarty International Center: An Unsung Hero for Global Health Research and Development. PMID- 28990903 TI - Congressman John E. Fogarty: A Champion for Global Health. PMID- 28990905 TI - The Fogarty International Center is Essential to Global Health Security. PMID- 28990906 TI - Plasmodium vivax Infection in Duffy-Negative People in Africa. PMID- 28990907 TI - Prevalence of and Factors Associated with Nephropathy in Diabetic Patients Attending an Outpatients Clinic in Harare, Zimbabwe: Methodological Issues. PMID- 28990908 TI - Prevalence of and Factors Associated with Nephropathy in Diabetic Patients Attending an Outpatient Clinic in Harare, Zimbabwe: Methodological Issues. PMID- 28990909 TI - Let's Eliminate Diseases, Not Institutes: The Case for the Fogarty International Center. PMID- 28990910 TI - Pulmonary Cystic Echinococcosis. PMID- 28990912 TI - Using Rainfall and Temperature Data in the Evaluation of National Malaria Control Programs in Africa. AB - Since 2010, the Roll Back Malaria (RBM) Partnership, including National Malaria Control Programs, donor agencies (e.g., President's Malaria Initiative and Global Fund), and other stakeholders have been evaluating the impact of scaling up malaria control interventions on all-cause under-five mortality in several countries in sub-Saharan Africa. The evaluation framework assesses whether the deployed interventions have had an impact on malaria morbidity and mortality and requires consideration of potential nonintervention influencers of transmission, such as drought/floods or higher temperatures. Herein, we assess the likely effect of climate on the assessment of the impact malaria interventions in 10 priority countries/regions in eastern, western, and southern Africa for the President's Malaria Initiative. We used newly available quality controlled Enhanced National Climate Services rainfall and temperature products as well as global climate products to investigate likely impacts of climate on malaria evaluations and test the assumption that changing the baseline period can significantly impact on the influence of climate in the assessment of interventions. Based on current baseline periods used in national malaria impact assessments, we identify three countries/regions where current evaluations may overestimate the impact of interventions (Tanzania, Zanzibar, Uganda) and three countries where current malaria evaluations may underestimate the impact of interventions (Mali, Senegal and Ethiopia). In four countries (Rwanda, Malawi, Mozambique, and Angola) there was no strong difference in climate suitability for malaria in the pre- and post-intervention period. In part, this may be due to data quality and analysis issues. PMID- 28990911 TI - Plasmodium Species Infecting Children Presenting with Malaria in Uganda. AB - Contributions of species other than Plasmodium falciparum to human malaria in sub Saharan Africa are uncertain. We collected blood from children aged 6 months to 10 years diagnosed with malaria by Giemsa-stained blood smears (176 subjects) or histidine rich protein-2-based rapid diagnostic tests (323 subjects) in 2016; 50 samples from each of 10 sites across Uganda were studied to identify infecting species. Of 499 available samples, 474 demonstrated plasmodial infection by polymerase chain reaction amplification of 18S ribosomal RNA genes, including P. falciparum in 472, Plasmodium malariae in 22, Plasmodium ovale in 15, and Plasmodium vivax in four; 435 were pure P. falciparum, two did not contain P. falciparum, and the remainder were mixed infections including P. falciparum. The prevalence of nonfalciparum species varied geographically. Stratifying based on recent history of indoor residual spraying (IRS) of insecticides, nonfalciparum infections were seen in 27/189 (14.8%) samples from sites that received and 13/285 (4.6%) samples from sites that did not receive IRS since 2010 (P = 0.0013). Overall, 39/474 (8.2%) samples from individuals diagnosed with malaria included nonfalciparum infections. Thus, a substantial proportion of episodes of malaria in Uganda include infections with plasmodial species other than P. falciparum. PMID- 28990913 TI - Declines in Malaria Burden and All-Cause Child Mortality following Increases in Control Interventions in Senegal, 2005-2010. AB - Malaria is endemic in Senegal. The national malaria control strategy focuses on achieving universal coverage for major interventions, with a goal of reaching preelimination status by 2018. Senegal began distribution of insecticide-treated nets (ITNs) and introduced artemisinin-based combination therapy in 2006, then introduced rapid diagnostic tests in 2007. We evaluated the impact of these efforts using a plausibility design based on malaria's contribution to all-cause under-five mortality (ACCM) and considering other contextual factors which may influence ACCM. Between 2005 and 2010, household ownership of ITNs increased from 20% to 63%, and the proportion of people sleeping under an ITN the night prior to the survey increased from 6% to 29%. Malaria parasite prevalence declined from 6% to 3% from 2008 to 2010 among children under five. Some nonmalaria indicators of child health improved, for example, increase of complete vaccination coverage from 58% to 64%; however, nutritional indicators deteriorated, with an increase in stunting from 16% to 26%. Although economic indicators improved, environmental conditions favored an increase in malaria transmission. ACCM decreased 40% between 2005 and 2010, from 121 (95% confidence interval [CI] 113-129) to 72 (95% CI 66-77) per 1,000, and declines were greater among age groups, epidemiologic zones, and wealth quintiles most at risk for malaria. After considering coverage of malaria interventions, trends in malaria morbidity, effects of contextual factors, and trends in ACCM, it is plausible that malaria control interventions contributed to a reduction in malaria mortality and to the impressive gains in child survival in Senegal. PMID- 28990914 TI - Strengthening Routine Health Information Systems to Target Malaria Control Implementation and Optimize Evaluation of Impact. PMID- 28990916 TI - Increasing the Impact of Impact Evaluation. PMID- 28990915 TI - Methodological Considerations for Use of Routine Health Information System Data to Evaluate Malaria Program Impact in an Era of Declining Malaria Transmission. AB - Coverage of malaria control interventions is increasing dramatically across endemic countries. Evaluating the impact of malaria control programs and specific interventions on health indicators is essential to enable countries to select the most effective and appropriate combination of tools to accelerate progress or proceed toward malaria elimination. When key malaria interventions have been proven effective under controlled settings, further evaluations of the impact of the intervention using randomized approaches may not be appropriate or ethical. Alternatives to randomized controlled trials are therefore required for rigorous evaluation under conditions of routine program delivery. Routine health management information system (HMIS) data are a potentially rich source of data for impact evaluation, but have been underused in impact evaluation due to concerns over internal validity, completeness, and potential bias in estimates of program or intervention impact. A range of methodologies were identified that have been used for impact evaluations with malaria outcome indicators generated from HMIS data. Methods used to maximize internal validity of HMIS data are presented, together with recommendations on reducing bias in impact estimates. Interrupted time series and dose-response analyses are proposed as the strongest quasi-experimental impact evaluation designs for analysis of malaria outcome indicators from routine HMIS data. Interrupted time series analysis compares the outcome trend and level before and after the introduction of an intervention, set of interventions or program. The dose-response national platform approach explores associations between intervention coverage or program intensity and the outcome at a subnational (district or health facility catchment) level. PMID- 28990917 TI - Assessing the Health Impact of Malaria Control Interventions in the MDG/Sustainable Development Goal Era: A New Generation of Impact Evaluations. PMID- 28990918 TI - Impact Evaluation of Malaria Control Interventions on Morbidity and All-Cause Child Mortality in Rwanda, 2000-2010. AB - The impressive decline in child mortality that occurred in Rwanda from 1996-2000 to 2006-2010 coincided with a period of rapid increase of malaria control interventions such as indoor residual spraying (IRS); insecticide-treated net (ITN) distribution and use, and improved malaria case management. The impact of these interventions was examined through ecological correlation analysis, and robust decomposition analysis of contextual factors on all-cause child mortality. Child mortality fell 61% during the evaluation period and prevalence of severe anemia in children 6-23 months declined 71% between 2005 and 2010. These changes in malaria morbidity and mortality occurred concurrently with a substantial increase in vector control activities. ITN use increased among children under five, from 4% to 70%. The IRS program began in 2007 and covered 1.3 million people in the highest burden districts by 2010. At the same time, diagnosis and treatment with an effective antimalarial expanded nationally, and included making services available to children under the age of 5 at the community level. The percentage of children under 5 who sought care for a fever increased from 26% in 2000 to 48% in 2010. Multivariable models of the change in child mortality between 2000 and 2010 using nationally representative data reveal the importance of increasing ITN ownership in explaining the observed mortality declines. Taken as a whole, the evidence supports the conclusion that malaria control interventions contributed to the observed decline in child mortality in Rwanda from 2000 to 2010, even in a context of improving socioeconomic, maternal, and child health conditions. PMID- 28990919 TI - The Future of Measuring Impact against Malaria: From Saving Lives to Eliminating Transmission. PMID- 28990920 TI - Malaria Control Interventions Contributed to Declines in Malaria Parasitemia, Severe Anemia, and All-Cause Mortality in Children Less Than 5 Years of Age in Malawi, 2000-2010. AB - Malaria control intervention coverage increased nationwide in Malawi during 2000 2010. Trends in intervention coverage were assessed against trends in malaria parasite prevalence, severe anemia (hemoglobin < 8 g/dL), and all-cause mortality in children under 5 years of age (ACCM) using nationally representative household surveys. Associations between insecticide-treated net (ITN) ownership, malaria morbidity, and ACCM were also assessed. Household ITN ownership increased from 27.4% (95% confidence interval [CI] = 25.9-29.0) in 2004 to 56.8% (95% CI = 55.6 58.1) in 2010. Similarly intermittent preventive treatment during pregnancy coverage increased from 28.2% (95% CI = 26.7-29.8) in 2000 to 55.0% (95% CI = 53.4-56.6) in 2010. Malaria parasite prevalence decreased significantly from 60.5% (95% CI = 53.0-68.0) in 2001 to 20.4% (95% CI = 15.7-25.1) in 2009 in children aged 6-35 months. Severe anemia prevalence decreased from 20.4% (95% CI: 17.3-24.0) in 2004 to 13.1% (95% CI = 11.0-15.4) in 2010 in children aged 6-23 months. ACCM decreased 41%, from 188.6 deaths per 1,000 live births (95% CI = 179.1-198.0) during 1996-2000, to 112.1 deaths per 1,000 live births (95% CI = 105.8-118.5) during 2006-2010. When controlling for other covariates in random effects logistic regression models, household ITN ownership was protective against malaria parasitemia in children (odds ratio [OR] = 0.81, 95% CI = 0.72 0.92) and severe anemia (OR = 0.82, 95% CI = 0.72-0.94). After considering the magnitude of changes in malaria intervention coverage and nonmalaria factors, and given the contribution of malaria to all-cause mortality in malaria-endemic countries, the substantial increase in malaria control interventions likely improved child survival in Malawi during 2000-2010. PMID- 28990921 TI - Implementing Impact Evaluations of Malaria Control Interventions: Process, Lessons Learned, and Recommendations. AB - As funding for malaria control increased considerably over the past 10 years resulting in the expanded coverage of malaria control interventions, so did the need to measure the impact of these investments on malaria morbidity and mortality. Members of the Roll Back Malaria (RBM) Partnership undertook impact evaluations of malaria control programs at a time when there was little guidance in terms of the process for conducting an impact evaluation of a national-level malaria control program. The President's Malaria Initiative (PMI), as a member of the RBM Partnership, has provided financial and technical support for impact evaluations in 13 countries to date. On the basis of these experiences, PMI and its partners have developed a streamlined process for conducting the evaluations with a set of lessons learned and recommendations. Chief among these are: to ensure country ownership and involvement in the evaluations; to engage stakeholders throughout the process; to coordinate evaluations among interested partners to avoid duplication of efforts; to tailor the evaluation to the particular country context; to develop a standard methodology for the evaluations and a streamlined process for completion within a reasonable time; and to develop tailored dissemination products on the evaluation for a broad range of stakeholders. These key lessons learned and resulting recommendations will guide future impact evaluations of malaria control programs and other health programs. PMID- 28990922 TI - Impact of Insecticide-Treated Net Ownership on All-Cause Child Mortality in Malawi, 2006-2010. AB - Insecticide-treated nets (ITNs) have been shown to be highly effective at reducing malaria morbidity and mortality in children. However, there are limited studies that assess the association between increasing ITN coverage and child mortality over time, at the national level, and under programmatic conditions. Two analytic approaches were used to examine this association: a retrospective cohort analysis of individual children and a district-level ecologic analysis. To evaluate the association between household ITN ownership and all-cause child mortality (ACCM) at the individual level, data from the 2010 Demographic and Health Survey (DHS) were modeled in a Cox proportional hazards framework while controlling for numerous environmental, household, and individual confounders through the use of exact matching. To evaluate population-level association between ITN ownership and ACCM between 2006 and 2010, program ITN distribution data and mortality data from the 2006 Multiple Indicator Cluster Survey and the 2010 DHS were aggregated at the district level and modeled using negative binomial regression. In the Cox model controlling for household, child and maternal health factors, children between 1 and 59 months in households owning an ITN had significantly lower mortality compared with those without an ITN (hazard ratio = 0.75, 95% confidence interval [CI] = 0.62-90). In the district-level model, higher ITN ownership was significantly associated with lower ACCM (incidence rate ratio = 0.77; 95% CI = 0.60-0.98). These findings suggest that increasing ITN ownership may have contributed to the decline in ACCM during 2006 2010 in Malawi and represent a novel use of district-level data from nationally representative surveys. PMID- 28990923 TI - Framework for Evaluating the Health Impact of the Scale-Up of Malaria Control Interventions on All-Cause Child Mortality in Sub-Saharan Africa. AB - Concerted efforts from national and international partners have scaled up malaria control interventions, including insecticide-treated nets, indoor residual spraying, diagnostics, prompt and effective treatment of malaria cases, and intermittent preventive treatment during pregnancy in sub-Saharan Africa (SSA). This scale-up warrants an assessment of its health impact to guide future efforts and investments; however, measuring malaria-specific mortality and the overall impact of malaria control interventions remains challenging. In 2007, Roll Back Malaria's Monitoring and Evaluation Reference Group proposed a theoretical framework for evaluating the impact of full-coverage malaria control interventions on morbidity and mortality in high-burden SSA countries. Recently, several evaluations have contributed new ideas and lessons to strengthen this plausibility design. This paper harnesses that new evaluation experience to expand the framework, with additional features, such as stratification, to examine subgroups most likely to experience improvement if control programs are working; the use of a national platform framework; and analysis of complete birth histories from national household surveys. The refined framework has shown that, despite persisting data challenges, combining multiple sources of data, considering potential contributions from both fundamental and proximate contextual factors, and conducting subnational analyses allows identification of the plausible contributions of malaria control interventions on malaria morbidity and mortality. PMID- 28990924 TI - Correction: The splicing regulator PTBP2 controls a program of embryonic splicing required for neuronal maturation. PMID- 28990925 TI - Tracking individual action potentials throughout mammalian axonal arbors. AB - Axons are neuronal processes specialized for conduction of action potentials (APs). The timing and temporal precision of APs when they reach each of the synapses are fundamentally important for information processing in the brain. Due to small diameters of axons, direct recording of single AP transmission is challenging. Consequently, most knowledge about axonal conductance derives from modeling studies or indirect measurements. We demonstrate a method to noninvasively and directly record individual APs propagating along millimeter length axonal arbors in cortical cultures with hundreds of microelectrodes at microsecond temporal resolution. We find that cortical axons conduct single APs with high temporal precision (~100 us arrival time jitter per mm length) and reliability: in more than 8,000,000 recorded APs, we did not observe any conduction or branch-point failures. Upon high-frequency stimulation at 100 Hz, successive became slower, and their arrival time precision decreased by 20% and 12% for the 100th AP, respectively. PMID- 28990927 TI - Frequency-dependent mobilization of heterogeneous pools of synaptic vesicles shapes presynaptic plasticity. AB - The segregation of the readily releasable pool of synaptic vesicles (RRP) in sub pools that are differentially poised for exocytosis shapes short-term plasticity. However, the frequency-dependent mobilization of these sub-pools is poorly understood. Using slice recordings and modeling of synaptic activity at cerebellar granule cell to Purkinje cell synapses of mice, we describe two sub pools in the RRP that can be differentially recruited upon ultrafast changes in the stimulation frequency. We show that at low-frequency stimulations, a first sub-pool is gradually silenced, leading to full blockage of synaptic transmission. Conversely, a second pool of synaptic vesicles that cannot be released by a single stimulus is recruited within milliseconds by high-frequency stimulation and support an ultrafast recovery of neurotransmitter release after low-frequency depression. This frequency-dependent mobilization or silencing of sub-pools in the RRP in terminals of granule cells may play a role in the filtering of sensorimotor information in the cerebellum. PMID- 28990926 TI - IRAK2 directs stimulus-dependent nuclear export of inflammatory mRNAs. AB - Expression of inflammatory genes is determined in part by post-transcriptional regulation of mRNA metabolism but how stimulus- and transcript-dependent nuclear export influence is poorly understood. Here, we report a novel pathway in which LPS/TLR4 engagement promotes nuclear localization of IRAK2 to facilitate nuclear export of a specific subset of inflammation-related mRNAs for translation in murine macrophages. IRAK2 kinase activity is required for LPS-induced RanBP2 mediated IRAK2 sumoylation and subsequent nuclear translocation. Array analysis showed that an SRSF1-binding motif is enriched in mRNAs dependent on IRAK2 for nuclear export. Nuclear IRAK2 phosphorylates SRSF1 to reduce its binding to target mRNAs, which promotes the RNA binding of the nuclear export adaptor ALYREF and nuclear export receptor Nxf1 loading for the export of the mRNAs. In summary, LPS activates a nuclear function of IRAK2 that facilitates the assembly of nuclear export machinery to export selected inflammatory mRNAs to the cytoplasm for translation. PMID- 28990929 TI - Multiparametric Magnetic Resonance Imaging for Active Surveillance of Prostate Cancer. AB - Active surveillance has gained popularity as an acceptable management option for men with low-risk prostate cancer. Successful utilization of this strategy can delay or prevent unnecessary interventions - thereby reducing morbidity associated with overtreatment. The usefulness of active surveillance primarily depends on correct identification of patients with low-risk disease. However, current population-wide algorithms and tools do not adequately exclude high-risk disease, thereby limiting the confidence of clinicians and patients to go on active surveillance. Novel imaging tools such as mpMRI provide information about the size and location of potential cancers enabling more informed treatment decisions. The term "multiparametric" in prostate mpMRI refers to the summation of several MRI series into one examination whose initial goal is to identify potential clinically-significant lesions suitable for targeted biopsy. The main advantages of MRI are its superior anatomic resolution and the lack of ionizing radiation. Recently, the Prostate Imaging-Reporting and Data System has been instituted as an international standard for unifying mpMRI results. The imaging sequences in mpMRI defined by Prostate Imaging Reporting and Data System version 2 includes: T2-weighted MRI, diffusion-weighted MRI, derived apparent-diffusion coefficient from diffusion-weighted MRI, and dynamic contrast-enhanced MRI. The use of mpMRI prior to starting active surveillance could prevent those with missed, high-grade lesions from going on active surveillance, and reassure those with minimal disease who may be hesitant to take part in active surveillance. Although larger validation studies are still necessary, preliminary results suggest mpMRI has a role in selecting patients for active surveillance. Less certain is the role of mpMRI in monitoring patients on active surveillance, as data on this will take a long time to mature. The biggest obstacles to routine use of prostate MRI are quality control, cost, reproducibility, and access. Nevertheless, there is great a potential for mpMRI to improve outcomes and quality of treatment. The major roles of MRI will continue to expand and its emerging use in standard of care approaches becomes more clearly defined and supported by increasing levels of data. PMID- 28990930 TI - Giant Bilateral Adrenal Myelolipoma. PMID- 28990928 TI - Mouse embryonic stem cells can differentiate via multiple paths to the same state. AB - In embryonic development, cells differentiate through stereotypical sequences of intermediate states to generate particular mature fates. By contrast, driving differentiation by ectopically expressing terminal transcription factors (direct programming) can generate similar fates by alternative routes. How differentiation in direct programming relates to embryonic differentiation is unclear. We applied single-cell RNA sequencing to compare two motor neuron differentiation protocols: a standard protocol approximating the embryonic lineage, and a direct programming method. Both initially undergo similar early neural commitment. Later, the direct programming path diverges into a novel transitional state rather than following the expected embryonic spinal intermediates. The novel state in direct programming has specific and uncharacteristic gene expression. It forms a loop in gene expression space that converges separately onto the same final motor neuron state as the standard path. Despite their different developmental histories, motor neurons from both protocols structurally, functionally, and transcriptionally resemble motor neurons isolated from embryos. PMID- 28990931 TI - Letter to the Editor concerning "Altered chondrocyte apoptosis status in developmental hip dysplasia in rabbits". PMID- 28990933 TI - Circulating osteocrin stimulates bone growth by limiting C-type natriuretic peptide clearance. AB - Although peptides are safe and useful as therapeutics, they are often easily degraded or metabolized. Dampening the clearance system for peptide ligands is a promising strategy for increasing the efficacy of peptide therapies. Natriuretic peptide receptor B (NPR-B) and its naturally occurring ligand, C-type natriuretic peptide (CNP), are potent stimulators of endochondral bone growth, and activating the CNP/NPR-B system is expected to be a powerful strategy for treating impaired skeletal growth. CNP is cleared by natriuretic peptide clearance receptor (NPR C); therefore, we investigated the effect of reducing the rate of CNP clearance on skeletal growth by limiting the interaction between CNP and NPR-C. Specifically, we generated transgenic mice with increased circulating levels of osteocrin (OSTN) protein, a natural NPR-C ligand without natriuretic activity, and observed a dose-dependent skeletal overgrowth phenotype in these animals. Skeletal overgrowth in OSTN-transgenic mice was diminished in either CNP- or NPR C-depleted backgrounds, confirming that CNP and NPR-C are indispensable for the bone growth-stimulating effect of OSTN. Interestingly, double-transgenic mice of CNP and OSTN had even higher levels of circulating CNP and additional increases in bone length, as compared with mice with elevated CNP alone. Together, these results support OSTN administration as an adjuvant agent for CNP therapy and provide a potential therapeutic approach for diseases with impaired skeletal growth. PMID- 28990932 TI - Uromodulin p.Cys147Trp mutation drives kidney disease by activating ER stress and apoptosis. AB - Uromodulin-associated kidney disease (UAKD) is caused by mutations in the uromodulin (UMOD) gene that result in a misfolded form of UMOD protein, which is normally secreted by nephrons. In UAKD patients, mutant UMOD is poorly secreted and accumulates in the ER of distal kidney epithelium, but its role in disease progression is largely unknown. Here, we modeled UMOD accumulation in mice by expressing the murine equivalent of the human UMOD p.Cys148Trp point mutation (UmodC147W/+ mice). Like affected humans, these UmodC147W/+ mice developed spontaneous and progressive kidney disease with organ failure over 24 weeks. Analysis of diseased kidneys and purified UMOD-producing cells revealed early activation of the PKR-like ER kinase/activating transcription factor 4 (PERK/ATF4) ER stress pathway, innate immune mediators, and increased apoptotic signaling, including caspase-3 activation. Unexpectedly, we also detected autophagy deficiency. Human cells expressing UMOD p.Cys147Trp recapitulated the findings in UmodC147W/+ mice, and autophagy activation with mTOR inhibitors stimulated the intracellular removal of aggregated mutant UMOD. Human cells producing mutant UMOD were susceptible to TNF-alpha- and TRAIL-mediated apoptosis due to increased expression of the ER stress mediator tribbles-3. Blocking TNF alpha in vivo with the soluble recombinant fusion protein TNFR:Fc slowed disease progression in UmodC147W/+ mice by reducing active caspase-3, thereby preventing tubule cell death and loss of epithelial function. These findings reveal a targetable mechanism for disease processes involved in UAKD. PMID- 28990934 TI - Mast cell hyperactivity underpins the development of oxygen-induced retinopathy. AB - Mast cells are classically thought to play an important role in protection against helminth infections and in the induction of allergic diseases; however, recent studies indicate that these cells also contribute to neovascularization, which is critical for tissue remodeling, chronic inflammation, and carcinogenesis. Here, we demonstrate that mast cells are essential for sprouting angiogenesis in a murine model of oxygen-induced retinopathy (OIR). Although mouse strains lacking mast cells did not exhibit retinal neovascularization following hypoxia, these mice developed OIR following infusion of mast cells or after injection of mast cell tryptase (MCT). Relative hypoxia stimulated mast cell degranulation via transient receptor potential ankyrin 1. Subsequent surges in MCT stimulated retinal endothelial cells to produce monocyte chemotactic protein-1 (MCP1) and angiogenic factors, leading to sprouting angiogenesis. Mast cell stabilizers as well as specific tryptase and MCP1 inhibitors prevented the development of OIR in WT mice. Preterm infants with early retinopathy of prematurity had markedly higher plasma MCT levels than age-matched infants without disease, suggesting mast cells contribute to human disease. Together, these results suggest therapies that suppress mast cell activity should be further explored as a potential option for preventing eye diseases and subsequent blindness induced by neovascularization. PMID- 28990937 TI - [What is new in 2017 European Society of Cardiology ST Elevation Myocardial Infarction guideline?] PMID- 28990936 TI - Olfactory receptor 544 reduces adiposity by steering fuel preference toward fats. AB - Olfactory receptors (ORs) are present in tissues outside the olfactory system; however, the function of these receptors remains relatively unknown. Here, we determined that olfactory receptor 544 (Olfr544) is highly expressed in the liver and adipose tissue of mice and regulates cellular energy metabolism and obesity. Azelaic acid (AzA), an Olfr544 ligand, specifically induced PKA-dependent lipolysis in adipocytes and promoted fatty acid oxidation (FAO) and ketogenesis in liver, thus shifting the fuel preference to fats. After 6 weeks of administration, mice fed a high-fat diet (HFD) exhibited a marked reduction in adiposity. AzA treatment induced expression of PPAR-alpha and genes required for FAO in the liver and induced the expression of PPAR-gamma coactivator 1-alpha (Ppargc1a) and uncoupling protein-1 (Ucp1) genes in brown adipose tissue (BAT). Moreover, treatment with AzA increased insulin sensitivity and ketone body levels. This led to a reduction in the respiratory quotient and an increase in the FAO rate, as indicated by indirect calorimetry. AzA treatment had similar antiobesogenic effects in HFD-fed ob/ob mice. Importantly, AzA-associated metabolic changes were completely abrogated in HFD-fed Olfr544-/- mice. To our knowledge, this is the first report to show that Olfr544 orchestrates the metabolic interplay between the liver and adipose tissue, mobilizing stored fats from adipose tissue and shifting the fuel preference to fats in the liver and BAT. PMID- 28990938 TI - [The new changes in the European Society of Cardiology 2017 Guidelines for the Management of Valvular Heart Disease]. PMID- 28990939 TI - Tenth categories of total and HDL cholesterol fail to independently predict death risk in middle-aged Turkish adults. AB - OBJECTIVE: The aim of this study was to delineate in detail the longitudinal association of total cholesterol (TC) and highdensity lipoprotein cholesterol (HDL-C) levels with overall mortality in middle-aged participants of the biennial Turkish Adult Risk Factor study. METHODS: Baseline lipid variables were analyzed in sex-specific deciles. A baseline age of 45 to 84 years as an inclusion criterion led to the enrollment of 2121 men and women. Cox regression analyses were performed. RESULTS: Deaths were recorded in 237 and 306 women and men, respectively, during a mean 8.85+/-4.4 years of follow-up. After adjustment for age, smoking status, lipid-lowering and antihypertensive drug usage, prevalent diabetes, and coronary heart disease, and using the lowest decile as referent, neither TC (p trend=0.94 and 0.96, respectively), nor HDL-C categories (p trend=0.20 and 0.31, respectively) were significantly predictive of mortality in either gender. TC deciles exhibited a gender difference insofar as hazard ratios in females tended to be reciprocal to those in males in deciles 2 through 5. CONCLUSION: The findings on TC deciles may be attributed to a comparatively higher death rate in the female (compared with male) bottom decile, reflecting the autoimmune process-induced elevated risk in the lowest decile. Observations on HDLC confirmed presumed pro-inflammatory conversion in levels >50 mg/dL. These results have important clinical implications. PMID- 28990935 TI - Caspase-11-mediated endothelial pyroptosis underlies endotoxemia-induced lung injury. AB - Acute lung injury is a leading cause of death in bacterial sepsis due to the wholesale destruction of the lung endothelial barrier, which results in protein rich lung edema, influx of proinflammatory leukocytes, and intractable hypoxemia. Pyroptosis is a form of programmed lytic cell death that is triggered by inflammatory caspases, but little is known about its role in EC death and acute lung injury. Here, we show that systemic exposure to the bacterial endotoxin lipopolysaccharide (LPS) causes severe endothelial pyroptosis that is mediated by the inflammatory caspases, human caspases 4/5 in human ECs, or the murine homolog caspase-11 in mice in vivo. In caspase-11-deficient mice, BM transplantation with WT hematopoietic cells did not abrogate endotoxemia-induced acute lung injury, indicating a central role for nonhematopoietic caspase-11 in endotoxemia. Additionally, conditional deletion of caspase-11 in ECs reduced endotoxemia induced lung edema, neutrophil accumulation, and death. These results establish the requisite role of endothelial pyroptosis in endotoxemic tissue injury and suggest that endothelial inflammatory caspases are an important therapeutic target for acute lung injury. PMID- 28990940 TI - Are oxidative stress markers helpful for diagnosing the disease and determining its complexity or extent in patients with stable coronary artery disease? AB - OBJECTIVE: The aim of this study was to investigate the relationship between oxidative/antioxidative stress markers and the diagnosis and complexity of coronary artery disease (CAD) in patients with stable CAD. METHODS: A total of 145 patients were enrolled in the study. Based on coronary angiography results, the patients were categorized into 2 groups: those without CAD (Group 1) and those with CAD (Group 2). The patients in Group 2 were also categorized into low score and moderate/high score groups according to their SYNTAX score. The serum malondialdehyde (MDA) and total antioxidant capacity (TAOC) levels of Group 1 and Group 2 were compared. Finally, MDA and TAOC levels were compared between the moderate/high-risk and low-risk groups formed according to SYNTAX score. RESULTS: There was a significant difference with respect to both serum TAOC and MDA levels between Group 1 and Group 2 (p=0.036 and p=0.029, respectively). The groups with a SYNTAX score 1-22 and with a SYNTAX score >22 were not significantly different with respect to serum TAOC or MDA level (p=0.582 and p=0.85, respectively). CONCLUSION: The serum MDA level was significantly higher and the TAOC level was significantly lower in patients with stable CAD compared to those without; however, these molecule levels failed to predict disease complexity in patients with stable CAD. PMID- 28990941 TI - Influence of coronary calcification patterns on hemodynamic outcome of coronary stenoses and remodeling. AB - OBJECTIVE: The histological characteristics of plaque may affect the hemodynamic outcome of a given coronary stenosis. In particular, the potential effect of volumetric calcium content and the topographical distribution in the lesion segment on physiological outcome has not yet been investigated. The aim of this study was to identify any potential correlation between patterns of calcification and the fractional flow reserve (FFR) and the coronary remodeling index (RMI). METHODS: A total of 26 stable angina pectoris and 34 acute coronary syndrome patients without persistent ST-segment elevation constituted the study population. FFR was used to assess 70 intermediate coronary stenosis lesions. After obtaining hemodynamic measurements, quantitative grayscale and virtual histology-intravascular ultrasound analyses were performed. The depth, length, and circumferential distribution of calcification of the lesions were also recorded. RESULTS: Within the analyzed segment (area of interest, lesion segment), FFR was correlated with maximal thickness of deep calcification (r= 0.285; p=0.021) and calcification angle (r=-0.396; p=0.001). In lesions with a calcification angle >180 degrees , the mean FFR value was significantly lower compared with those <180 degrees (0.64+/-0.17 vs. 0.78+/-0.08; p=0.024). RMI was correlated with maximal angle of superficial (r=-0.437; p<0.001) and deep (r=0.425; p<0.001) calcification. RMI was correlated with maximal thickness of superficial (r=-0.357; p=0.003) and deep (r=0.417; p<0.001) calcification. RMI was also correlated with FFR (r=-0.477; p<0.001). CONCLUSION: This study demonstrated that the geometry, location, and amount of calcification of a plaque could affect hemodynamic and anatomical outcome measures in functionally significant stenoses by affecting vessel wall compliance. PMID- 28990942 TI - [Herbal supplement usage in cardiac patients]. AB - OBJECTIVE: Complementary and alternative medicine (CAM) has become more and more widespread around the world. CAM is a broad term that refers to all medical healthcare services, methods, and practices that are not part of standard medical care, as well as the accompanying theories and beliefs. The aim of the present study was to investigate the use of herbal medicinal products in cardiac patients, as well as the methods of administration of the products. METHODS: This descriptive cross-sectional study included 199 patients aged over 18 years who were hospitalized in the Defne Hospital department of cardiology and volunteered to participate in a 20-item survey between April 2016 and June 2016. RESULTS: The study results indicated that 28.6% (n=57) of patients were using herbal products and 71.6% (n=142) said they did not. Only 14.03% (n=8) of those who used herbal products said they used them in consultation with their physician; 85.9% (n=49) had used herbal medicine without consulting their doctor. Of the participants with hypertension, 35.7% of them reported using herbal medicinal products. Of these, 22.5% of them were consuming lemon, 17.5% pomegranate syrup, and 17.5% green tea. Of the participants with cardiovascular diseases, 23.5% of them stated that they were taking herbal products. Of these, 25% were consuming green tea, 25% ginger, and 18.8% sage. CONCLUSION: Herbal medicinal supplements were used by a large portion of the cardiac patients in this study. Furthermore, most of the patients stated that they were using these products without informing their physician, a practice that can have unwanted consequences. PMID- 28990943 TI - [Do Turkish reimbursement recommendations cover current European Lipid Guidelines? A retrospective analysis of patients presenting with first acute coronary syndrom]. AB - OBJECTIVE: This study was a comparison of the statin therapy protocol issued by the European Society of Cardiology (ESC) and the Ministry of Health's Health Implementation Directive (SUT) in Turkey, performed in order to assess the adequacy of hyperlipidemia treatment indications for primary prevention. METHODS: A total of 582 patients with first acute coronary syndrome were included in the study. Patients with noncritical stenosis observed on coronary angiography or a history of atherosclerotic disease were excluded. The risk calculation was determined using age, sex, smoking status, presence of diabetes mellitus, total cholesterol, and lipoprotein levels. Statin treatment indications were evaluated according to the ESC guidelines (2016) and the SUT (2016). RESULTS: Statin treatment was indicated for 96% of diabetic patients, and according to the ESC, it was appropriate for 13.5% of nondiabetic patients, while the SUT recommendation included 13.3% of nondiabetic patients (p<0.05). For patients younger than 60 years of age, the SUT had more guidelines than the ESC; however, for patients aged 70 to 90, the ESC had more guidelines than the SUT. For patients over 90, the indications were the same. For patients with low-density lipoprotein-cholesterol (LDL-C) >190 mg/dL there was greater discrepancy between the SUT and ESC guidelines. According to the SUT, all patients >190 mg/dL are to receive treatment. The ESC had more guidelines than the SUT for cases of LDLC <160b mg/dL. CONCLUSION: The scope of the SUT guidelines is generally not narrower than the ESC indications. However, the indications for patients >60 years of age and those with LDL-C >160 mg/ dL should be reassessed, as they are more limited than those of the ESC. A new treatment algorithm should be defined. PMID- 28990944 TI - The opinion of Turkish cardiologists on current malpractice system and an alternative patient compensation system proposal: PCS study group. AB - OBJECTIVE: Cardiologists participate in the diagnosis and interventional treatment of numerous high-risk patients. The goal of this study was to investigate how the current malpractice system in Turkey influences cardiologists' diagnostic and interventional behavior and to obtain their opinions about an alternative patient compensation system. METHODS: The present cross-sectional study assessed the practice of defensive medicine among cardiologists who are actively working in various types of workplace within the Turkish healthcare system. A 24-item questionnaire was distributed to cardiology residents, specialists, and academics in Turkey in print format, by electronic mail, or via cell phone message. RESULTS: A total of 253 cardiologists responded to the survey. Among them, 29 (11.6%) had been sued for malpractice claims in the past. Of the cardiologists who had been sued, 2 (6.9%) had been ordered to pay financial compensation, and 1 (3.4%) was given a sentence of imprisonment due to negligence. In all, 132 (52.8%) of the surveyed cardiologists reported that they had changed their practices due to fear of litigation, and 232 (92.8%) reported that they would prefer the new proposed patient compensation system to the current malpractice system. Among the cardiologists surveyed, 78.8% indicated that malpractice fear had affected their decision-making with regard to requesting computed tomography angiography or thallium scintigraphy, 71.6% for coronary angiography, 20% for stent implantation, and 83.2% for avoiding treating high-risk patients. CONCLUSION: The results of this survey demonstrated that cardiologists may request unnecessary tests and perform unneeded interventions due to the fear of malpractice litigation fear. Many also avoid high-risk patients and interventions. The majority indicated that they would prefer the proposed alternative patient compensation system to the current malpractice system. PMID- 28990945 TI - An alternative treatment for iatrogenic right ventricular puncture in primary percutaneous intervention. AB - Right ventricle perforation is an uncommon, but potentially fatal, possible complication of pericardiocentesis. We presented a case of right ventricular perforation that developed during urgent pericardiocentesis due to tamponade. This case was successfully treated with the incremental removal of the drainage catheter, replacing it with a smaller catheter at 10-minute intervals. This may be an alternative option to treat iatrogenic right ventricle puncture occurring during pericardiocentesis without cardiac surgery or a vascular closure device. PMID- 28990947 TI - Ablation of epicardial premature ventricular contractions in a patient with ischemic cardiomyopathy and implementation of cardiac resynchronization therapy in the same procedure. AB - Premature ventricular contractions (PVCs) can cause clinical deterioration in patients with heart failure and increase the frequency of shocks delivered by an implantable cardioverter defibrillator (ICD). Epicardial PVC/ventricular tachycardia (VT) is seen less often in ischemic cardiomyopathy. Radiofrequency catheter ablation is the most effective treatment option for the management of PVC/VT and can improve cardiac function. Presently described is a patient with ischemic cardiomyopathy and frequent PVCs and VT runs with multiple ICD therapies who was treated with simultaneous radiofrequency catheter ablation in the anterior interventricular vein and cardiac resynchronization therapy defibrillator upgrade in the same procedure. PMID- 28990946 TI - Stent and implantable cardioverter defibrillator implantation in medically resistant vasospastic angina patient. AB - Vasospastic angina, also known as Prinzmetal's angina, is thought to occur due to vascular hyper-reactivity to various stimuli. Response to medical therapy is usually good; however, 1 out of 5 patients has resistant symptoms. Rarely, potentially lethal arrhythmias can occur due to vasospasm, and those patients are reported to have a poorer prognosis. Presently described is a case of resistant vasospastic angina with persistent symptoms under calcium channel blocker and nitrate treatment. The patient presented with hemodynamically unstable rapid-rate ventricular tachycardia, which was quite resistant to recurrent cardioversion. She was treated with stent implantation for definite vasospastic segments of the coronaries, in combination with medical therapy. An implantable cardioverter defibrillator was also implanted for secondary prevention of ventricular arrhythmia, as vasospasm was considered to be a diffuse disease without a certain definitive treatment. PMID- 28990948 TI - Case series of three different scenarios with drug-induced Brugada patterns: fact or fiction? AB - Brugada syndrome is an inherited cardiac arrhythmia condition characterized by coved-type ST elevation and J point elevation of at least 2 mm in at least 2 of the right precordial electrocardiogram (ECG) leads (V1-3). An increasing number of noncardiac agents, including psychotropic and anesthetic drugs, have been shown to induce a characteristic Brugada ECG pattern, predisposing the patient to fatal ventricular arrhythmias. However, there are scarce data regarding the clinical significance. In this case series, a typical Brugada pattern was unmasked by lithium, valproic acid, and thiocolchicoside; however, the clinical scenario was different in all 3 cases, ranging from an asymptomatic patient to sudden cardiac arrest. PMID- 28990949 TI - Exceptional cause of chest pain: idiopathic ascending aortitis. AB - Idiopathic ascending aortitis is an insidious disease most often encountered during an evaluation for other cardiovascular and connective tissue diseases. To the best of our knowledge, admission to an emergency department with chest pain due to idiopathic ascending aortitis has not been reported before. Herein, the case of a 46-year-old man with chest and back pain symptoms that were discovered to be secondary solely to idiopathic ascending aortitis is described. PMID- 28990950 TI - A rare complication of chronic granulomatous disease in a child: constrictive aspergillus pericarditis. AB - A 3-year-old girl with the diagnosis of chronic granulomatous disease (CGD) was hospitalized for bronchopneumonia and congestive heart failure. Her medical history included methylprednisolone medication for autoimmune gastric outlet obstruction. Computed tomography revealed pneumonic infiltrations and pericardial thickening. A pulsed-wave Doppler recording revealed E/A >1. During a pericardiectomy, multiple islands of thick, firm-walled, fibrinous exudate containing, small abscess formations were observed. Histopathological evaluation of pericardial tissue revealed granulomatous inflammation. Aspergillus fumigatus was cultured from the abscess. In conclusion, development of constrictive aspergillus pericarditis should be considered in patients with CGD because immediate initiation of antifungal management with aggressive surgical treatment is life-saving. PMID- 28990951 TI - Testosterone replacement therapy and cardiovascular events. AB - A low testosterone level and hypogonadism are associated with cardiovascular disease. Aging, chronic health problems, and obesity are all associated with a low testosterone level as well as the presence and severity of cardiovascular disease. Testosterone is increasingly prescribed for patients with clinical hypogonadism and a low testosterone level. The information we have is still contradictory regarding testosterone replacement therapy (TRT) and its association with adverse cardiovascular events. Older patients and patients who are susceptible to cardiovascular diseases could be at risk with a testosterone prescription. This is a review of the literature to discuss the cardiovascular safety of TRT. PMID- 28990952 TI - Case Image: Delayed therapy and syncope due to excessive charging time in a patient with implantable defibrillator during a fast ventricular tachycardia episode. PMID- 28990953 TI - Case Image: Assessment of isolated cleft mitral valve by live/real-time three dimensional transesophageal echocardiography. PMID- 28990954 TI - Case Image: Cardiac metastasis of cervical cancer. PMID- 28990955 TI - Case Image: Acute coronary syndrome accompanying transient ischemic attack: an unusual presentation of myxoma. PMID- 28990956 TI - To extract, or not to extract: that is the question. PMID- 28990957 TI - Authors reply. PMID- 28990958 TI - Chronic obstructive pulmonary disease in the long-term care setting: current practices, challenges, and unmet needs. AB - : Chronic obstructive pulmonary disease (COPD) is a prevalent and disabling disorder in the United States, especially affecting older individuals, women, and those with a history of smoking. Studies show that COPD may be underrepresented, underdiagnosed, and undertreated in elderly patients residing in long-term care (LTC) facilities. The quality of care for LTC residents with COPD is heterogeneous in regard to both the facility and the patient. For LTC facilities, care should be driven by staff education, interstaff communication, and interfacility communication. From the perspective of the LTC patient, choice of medication and device should be based on appropriate diagnosis, comorbidities, ability to perform treatment, and patient preferences. Nebulization is currently underutilized in LTC settings, although it would benefit older patients with low peak inspiratory flow, cognitive impairment, and/or physical impairment, which may preclude them from using other inhalation devices. Authors developed a COPD treatment algorithm that focuses on three primary patient aspects to consider when deciding on respiratory device in patients in LTC facilities: inspiratory flow, hand dexterity and coordination, and cognitive capacity. PMID- 28990959 TI - Ethical and psychiatric boundaries in transplant psychiatry. PMID- 28990960 TI - Anesthesia Simulator-Based Functional Capacity Evaluation of an Anesthesiologist After Radial Fracture: A Case Report. AB - We used simulation as a job-specific functional capacity evaluation method after a distal radius fracture in an anesthesiologist. Treatment included open reduction followed by an internal fixation with an arthrodesis plate. The patient performed simulated anesthesia inductions to assess her response to endotracheal intubation, bag-mask ventilation, and the manual opening of the airway. Data collected helped to guide the rehabilitation protocol, and to assess pain and the time to safely return to work. The patient began her clinical duties after 7 weeks of therapy and was able to fully perform her daily tasks with confidence, and full functional capacity. PMID- 28990961 TI - Six Month Follow-Up of a Patient With a Retained Fascia Iliaca Catheter: A Case Report. AB - Retained catheters are a rare but known complication of continuous peripheral nerve block. To date there have been several case reports of retained catheters but none that include longer-term follow-up of the patient experience and outcomes. Here, we present the case of a retained fascia iliaca catheter used for analgesia after total hip arthroplasty that fractured during removal and was ultimately never retrieved. The patient initially experienced paresthesias emanating from the site of continuous peripheral nerve block catheter placement, but these issues resolved completely over several weeks. No infectious or serious sequelae were encountered during 6 months of follow-up. PMID- 28990962 TI - Two-Stage Technique Used to Manage Severe Upper Airway Obstruction and Avoid Surgical Tracheostomy: A Case Report. AB - Severe upper airway obstruction is commonly managed with surgical tracheostomy under local anesthesia. We present a 49-year-old woman with postradiotherapy laryngeal fixation and transglottic stenosis for dilation of a pharyngeal stricture who refused elective tracheostomy. A 2-stage technique was used, which involved an awake fiberoptic intubation, followed by the transtracheal insertion of a Cricath needle and ventilation using an ejector-based Ventrain device. We discuss management aspects of this clinical scenario and the principles by which the Ventrain works. PMID- 28990963 TI - Terrible Twos or Early Signs of Psychopathology? Developmental Patterns in Early Identified Preschoolers With Cochlear Implants Compared With Hearing Controls. AB - OBJECTIVE: Cochlear implants (CIs) have dramatically improved the lives of children who are deaf or hard of hearing; however, little is known about its implications for preventing the development of psychiatric symptoms in this at risk population. This is the first longitudinal study to examine the early manifestation of emotional and behavioral disorders and associated risk and protective factors in early identified preschoolers with CIs compared with hearing peers. DESIGN: Participants were 74 children with CIs and 190 hearing controls between ages 1 and 5 years (mean age, 3.8 years). Hearing loss was detected using the Newborn Hearing Screening in The Netherlands and Flanders. Parents completed the Early Childhood Inventory-4, a well-validated measure, to evaluate the symptoms of DSM-IV-defined psychiatric disorders, during three consecutive years. Language scores were derived from each child's medical notes. RESULTS: Children with CIs and hearing controls evidenced comparable levels of disruptive behavior and anxiety/depression (which increased with age in both groups). Greater proficiency in language skills was associated with lower levels of psychopathology. Early CI and longer duration of CI use resulted in better language development. In turn, higher early language skills served as a protective factor against the development of disruptive behavior symptoms. CONCLUSIONS: This longitudinal study uniquely shows that improvement in language skills mitigates the development of early signs of psychopathology. Early identification of hearing loss and CIs help children improve their language skills. PMID- 28990964 TI - A Concept Analysis of Palliative Care Nursing: Advancing Nursing Theory. AB - The American Association of Colleges of Nursing specifies that all nurses must be prepared to deliver high-quality palliative care upon entry into practice. To achieve this aim, a clear understanding of palliative care nursing is needed. The Walker and Avant model for concept analysis was used to review and analyze relevant literature from 2000 to 2016. The authors utilized findings of this extensive review to develop a concept model and other practical resources for guiding nurses, educators, and researchers in applying and evaluating competence in the delivery of high-quality palliative nursing care. PMID- 28990965 TI - Calling to Nursing: Concept Analysis. AB - The aims of this article are (a) to analyze the concept of a calling as it relates nursing and (b) to develop a definition of calling to nursing with the detail and clarity needed to guide reliable and valid research. The classic steps described by Walker and Avant are used for the analysis. Literature from several disciplines is reviewed including vocational psychology, Christian career counseling, sociology, organizational management, and nursing. The analysis provides an operational definition of a calling to nursing and establishes 3 defining attributes of the concept: (a) a passionate intrinsic motivation or desire (perhaps with a religious component), (b) an aspiration to engage in nursing practice, as a means of fulfilling one's purpose in life, and (c) the desire to help others as one's purpose in life. Antecedents to the concept are personal introspection and cognitive awareness. Positive consequences to the concept are improved work meaningfulness, work engagement, career commitment, personal well-being, and satisfaction. Negative consequences of having a calling might include willingness to sacrifice well-being for work and problems with work life balance. Following the concept analysis, philosophical assumptions, contextual factors, interdisciplinary work, research opportunities, and practice implications are discussed. PMID- 28990966 TI - "It Feels More Real": An Interpretive Phenomenological Study of the Meaning of Video Games in Adolescent Lives. AB - The pervasiveness of video gaming among adolescents today suggests a need to understand how gaming affects identity formation. We interviewed 20 adolescents about their experiences of playing, asking them to describe how they used games and how game playing affected their real-world selves. Adolescents presented a complicated developmental picture: gaming placed players into virtual worlds that felt "real"; games were used to practice multiple identities; and gaming, often undertaken within a world of hyperviolence, provided stress relief, feelings of competence, and relaxation. Gaming occurred in complex "virtual" but "real" social arenas where adolescents gathered to interact, emulate, and develop identities. PMID- 28990968 TI - Improvements in Radiation Monitoring Trending. AB - One of the main goals for Radiation Safety Professionals is to help maintain radiation worker doses below administrative control levels. In the radiation safety field there is an increasing recognition of the value of dosimetry-related data that can be used to enhance safety programs and regulatory compliance. Mining radiation dosimetry data and rendering results in the form of dashboards provides insights for the Radiation Safety Professionals that could help improve the radiological protection programs effectiveness, enhances quality, and reduces cost. Quite often the professionals spend more time assembling data than analyzing for trends and acting to improve the radiation safety program. Data analysis tools were developed allowing the radiation safety professionals to perform surveillance on key parameters in the dosimetry program that can help identifying risks and insure early intervention. More than 2,200 institutions chosen from different industries were surveyed for more than 2 years after the implementation of this tool. Four indicators: dose per participant, collective dose, dosimeter return compliance, and number of workers exceeding ALARA levels were chosen as meaningful parameters in characterizing the health of the program. These parameters were tracked, analyzed, and compared to benchmarks developed based on more than 1 million monitored workers. PMID- 28990967 TI - The Pediatric Cardiac Intensive Care Unit Parental Stress Model: Refinement Using Directed Content Analysis. AB - This descriptive, qualitative study used directed content analysis to explore and clarify specific foci of parental stress for mothers of infants with complex congenital heart disease in the pediatric cardiac intensive care unit (PCICU). The PCICU Parental Stress Model was used as the guiding theoretical framework. Three focus groups were conducted with 14 mothers of infants who were being cared for in a PCICU at a large mid-Atlantic children's hospital. Data provided themes to support and refine the PCICU Parental Stress Model that can be used to guide practice, education, and future research in this unique population and setting. PMID- 28990969 TI - Dosimetry in Radiosynoviorthesis: 90Y VS. 153Sm. AB - Although there are several radionuclides suitable for radiosynoviorthesis (RSO), not all of them can irradiate deeper synovium. Yttrium-90 (Y) is the beta radionuclide with more penetration range; therefore, it is predominantly used to treat knees. The aim of this paper is to highlight several dosimetry concepts to compare Y and Sm, also discussing the feasibility of implementing a dose planning methodology for both in RSO. The MCNPX Monte Carlo nuclear code version 2.6 was used for calculating S-values from which the activity to be injected into the joint was obtained. This activity is considered sufficient to deliver a 100-Gy absorbed dose in 1 mm of synovial tissue. The simulated mathematical model consisted of a system formed by several cylindrical slabs of 1-mm thickness, aligned consecutively. The different areas of the cylinder base simulate several synovial membrane sizes. The effective treatment range for each radionuclide was also calculated. Quantification of the synovial joint features (synovial thickness and synovial surface) by diagnostic imaging, such as magnetic resonance (MRI) combined with a Monte Carlo simulation, can be used to achieve a treatment planning strategy in RSO with the available radionuclides. PMID- 28990970 TI - Impact of Mother-Daughter Relationship on Hypertension Self-management and Quality of Life: Testing Dyadic Dynamics Using the Actor-Partner Interdependence Model. AB - BACKGROUND: Although hypertension (HTN) treatment rates are similar across age groups of women, effective control is significantly worse among older women. Only 20% of hypertensive women aged 70 to 79 years have controlled blood pressure. OBJECTIVES: The purpose of this longitudinal study was to test the effects of the quality of mother-daughter relationship, inner strength, and control on HTN self management and health-related quality of life (HRQOL) for both members of the dyad at 6 months. The Actor-Partner Interdependence Model was used to examine the direct ("actor") and indirect ("partner") effects of 46 dyads. RESULTS: The mothers' perceived relationship quality with daughters directly impacted their own self-management of HTN and HRQOL while also indirectly affecting their daughters' self-management. Similarly, the daughters' perceived strength of their relationship with their mothers directly influenced their self-management and HRQOL and indirectly affected their mothers' self-management and HRQOL. PMID- 28990971 TI - A nonpharmacologic approach to managing insomnia in primary care. AB - Insomnia, or inadequate or poor sleep leading to significant distress or impairment in functioning, is a prevalent disorder treated by primary care providers (PCPs). With millions of people across the United States suffering from insomnia, PCPs must understand the disorder's pathophysiology, perpetuating factors, and treatment, as well as its effect on patient health and the economy. Although PCPs traditionally treat insomnia with pharmaceuticals, behavioral measures are effective and should be used whenever possible. This article reviews clinically relevant principles of diagnosing and treating insomnia, highlighting nonpharmacologic treatments. PMID- 28990972 TI - Managing chest pain in patients with concomitant left bundle-branch block. AB - Diagnosis and timely management of acute myocardial infarction (MI) relies heavily on the ST-segment elevation sum. Presence of concomitant left bundle branch block (LBBB) in patients presenting with possible acute MI presents a diagnostic dilemma. The LBBB pattern distorts ST-segment changes, delaying or preventing accurate diagnosis. This article reviews the Sgarbossa criteria and ST/S ratio and presents a treatment algorithm that may help improve patient care and reduce morbidity and mortality. PMID- 28990973 TI - The Issue of Gadolinium Retained in Tissues: Insights on the Role of Metal Complex Stability by Comparing Metal Uptake in Murine Tissues Upon the Concomitant Administration of Lanthanum- and Gadolinium Diethylentriamminopentaacetate. AB - OBJECTIVES: The aim of the study was to explore the role of the stability of metal complexes in the processes that lead to the metal retention in the brain and other tissues of mice administered with lanthanides-based contrast agents. This issue was tackled by the simultaneous injection of gadolinium (Gd) diethylentriamminopentaacetate (DTPA) and lanthanum-DTPA, which have the same charge and structure but differ in their thermodynamic stability by 3 orders of magnitude. MATERIALS AND METHODS: A total of 20 healthy BALB/c mice were administered by a single intravenous injection with a dose consisting of 0.6 mmol La-DTPA/kg and 0.6 mmol Gd-DTPA/kg. Then the animals were killed at different time points: 4, 24, 48, and 96 hours (5 mice each group).In an additional protocol, 5 mice were administered with 9 doses of 0.3 mmol La-DTPA/kg and 0.3 mmol of Gd-DTPA/kg every 2 days over a period of 3 weeks. The sacrifice time was set to 3 weeks after the last administration. After sacrifice, the Gd and La content in liver, spleen, kidney, muscle, cerebrum, cerebellum, bone, eye, skin, blood, and urine was determined by inductively coupled plasma-mass spectrometry. RESULTS: A general decrease in the content of both the lanthanides was observed upon delaying the sacrifice time. At relatively short times after the injection (up to 96 hours), in the spleen, kidney, muscle, skin, and eye, almost the same content of La and Gd was detected, whereas in the cerebrum, cerebellum, bones, and liver, the amount of retained La decreased much slower than that of Gd, yielding a progressive increase in La/Gd ratio. The amount of retained La in the various tissues 21 days after the last of 9 administrations of La-DTPA and Gd DTPA was always significantly higher than that of Gd. The concentration of both La and Gd decreased rapidly both in blood and in urine samples. DISCUSSION: The departure from the 1:1 ratio in the amounts of La and Gd determined in the investigated tissues has been used to gain information on the role of the complex stability and "wash-out" kinetics. The behavior of the less s' La-DTPA highlights processes occurring for Gd-DTPA at a slower rate.The herein obtained results support the view that most of the La/Gd retained in the brain arises from the intact chelate that has extravasated immediately after the intravenous administration. Long-term deposition of metal ions from internal reservoirs seems particularly relevant for liver and spleen. PMID- 28990974 TI - Iodine and Fat Quantification for Differentiation of Adrenal Gland Adenomas From Metastases Using Third-Generation Dual-Source Dual-Energy Computed Tomography. AB - OBJECTIVES: The aim of this study was to investigate the value of third generation dual-source dual-energy computed tomography (DECT) iodine and fat quantification in differentiating adrenal gland adenomas from metastases. MATERIALS AND METHODS: Sixty-two patients (38 men and 24 women; mean age, 69.1 years) underwent clinically indicated DECT of the abdomen on a third-generation dual-source scanner. Examinations were retrospectively included due to detected adrenal masses. For each adrenal lesion, unenhanced and contrast-enhanced attenuation values, as well as dual-energy iodine density and fat fraction, were recorded. Additional magnetic resonance imaging data, positron emission tomography/computed tomography scans, interval imaging follow-up, and histopathological analysis were used as the reference standard for all adrenal lesions. Mean values of unenhanced and contrast-enhanced attenuation, as well as material densities, were compared between adenomas, metastases, and normal adrenal glands. Furthermore, the diagnostic accuracy of unenhanced, contrast enhanced, and material density analysis was assessed between adrenal adenomas and metastases. RESULTS: Adrenal adenomas showed significant differences regarding iodine density and fat fraction values (1.3 +/- 0.4 mg/mL and 34.2% +/- 12.6%) in comparison with adrenal metastases (3.2 +/- 1.4 mg/mL and 10.7% +/- 7.8%) and normal adrenal glands (1.7 +/- 0.6 mg/mL and 18.7% +/- 12.0%) (all P <= 0.004). Analysis of unenhanced attenuation values revealed no significant differences between healthy adrenal parenchyma (19.1 +/- 15.6 HU) and adrenal metastases (26.9 +/- 16.2 HU) (P = 0.135). Iodine density and fat fraction analysis showed significantly higher diagnostic accuracy for the diagnosis of adenomas (sensitivity, 97% and 89%; specificity, 96% and 89%, respectively) compared with unenhanced and contrast-enhanced evaluation (sensitivity, 65% and 58%; specificity, 73% and 85%, respectively) (P <= 0.023). The combined diagnostic value of iodine density and fat fraction analysis revealed a sensitivity of 97% and a specificity of 100%. CONCLUSIONS: Third-generation dual-source DECT iodine and fat quantification allow for differentiation between adrenal adenomas and metastases with high diagnostic accuracy. PMID- 28990975 TI - Endoscopic Features of Varices Involving Lacrimal Sac and Nasolacrimal Duct. PMID- 28990976 TI - Orbital Inflammation as a Presenting Sign for CREST Syndrome. AB - A 61-year-old male was referred with a week's history of a painful and swollen left eye. Examination revealed normal visual acuities, left proptosis and global restriction of ocular ductions, and subretinal fluid at the macula. CT imaging confirmed thickening of the posterior scleral coat, with an associated choroidal effusion. Serology revealed positive antinuclear antibodies with a centromere staining pattern; subsequent rheumatology review revealed extensive telangiectasia with digital ulceration in both hands, and a diagnosis of limited cutaneous systemic sclerosis was made. Orbital inflammatory disease is often the initial presentation of systemic diseases such as sarcoidosis, granulomatosis with polyangiitis, and IgG4 disease. Limited cutaneous systemic sclerosis is rarely encountered in the context of orbital inflammation, but is a further systemic association, reminding the clinician of the diagnostic importance of peripheral symptoms and serological markers in patients presenting with orbital inflammation and scleritis. PMID- 28990977 TI - An Eye for an Eye and a Tooth for a Tooth! PMID- 28990978 TI - Bicanalicular Canaliculops and its Dacryoendoscopic Findings. AB - Canaliculops is a noninflammatory ectasia of the canaliculus and so far only 7 histopathologically confirmed cases have been reported worldwide. The authors present a middle aged female with right-sided bicanalicular cystic swellings associated with punctal agenesis. Ultrasound biomicroscopy showed a cystic dilatation of the canaliculus and dacryoendoscopy showed a cavity lined by whitish canalicular mucosa, thrown into numerous irregular folds with a blind medial end. Histopathological examination confirmed the diagnosis of canaliculops. To the best of authors' knowledge, this is the first description of a bicanalicular canaliculops and its dacryoendoscopic findings. PMID- 28990979 TI - Mortality After High-Energy Pelvic Fractures in Patients of Age 65 Years or Older. AB - OBJECTIVES: To document in-hospital and 1-year mortality rates after high-energy pelvic fracture in patients 65 years of age or older as compared to a younger cohort. DESIGN: Retrospective review. SETTING: Urban Level 1 academic trauma center. PATIENTS: Seventy consecutive patients 65 years of age and older treated for pelvic fracture resulting from high-energy mechanism from 2008 to 2011. A total of 140 patients 18-64 years of age were matched to the study population based on mechanism of injury and OTA Code 61 subtype for comparison. INTERVENTION: Review of demographics, injury characteristics, hospital management, and mortality. MAIN OUTCOME MEASUREMENTS: Mortality. RESULTS: The overall inpatient mortality rate was 10%. The older cohort exhibited an inpatient mortality rate 3 times higher than the younger cohort (18.6% vs. 5.7%, P = 0.003). There was no difference in mortality 1 year post discharge (5.3% vs. 3.8%, P = 0.699). No significant differences in initial Glasgow Coma Scale or Injury Severity Score were identified (GCS 12.9 vs. 12.4, P = 0.363; ISS 24.7 vs. 23.4, P = 0.479). Multivariate analysis identified the Charlson Comorbidity Index (CCI) (P = 0.012) and Abbreviated Injury Scale (AIS)-chest (P = 0.005) as independent predictors of in-hospital mortality, and CCI (0.005) and AIS-abdomen (0.012) for 1-year mortality. CONCLUSIONS: After controlling for mechanism of injury and pelvic fracture classification, we found that adults >=65 and those with multiple comorbidities were more likely to die in the hospital than younger adults. However, mortality within 1-year postdischarge was low and did not differ between groups. This is in sharp contrast to the high rates of postdischarge mortality observed in elderly patients with a hip fracture. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence. PMID- 28990981 TI - Telemedicine Applications in Obstetrics and Gynecology. AB - This article reviews principles to consider when setting up a telemedicine (TM) program to provide care to women in the field of obstetrics and gynecology. There are different types of TM encounters and clinical applications vary widely. The consensus among patients and providers is that TM is convenient to provide needed subspecialty medical care when it is not available locally. These programs are clinically successful, but economic and cost-effectiveness data are lacking. Federal reimbursement policy is limited for TM. State policy on coverage and reimbursement varies significantly from state to state and is the main driver on whether TM programs are successful. PMID- 28990982 TI - Futuristic Look at Genetic and Birth Defect Diagnoses and Treatments. AB - One aim of prenatal care is to provide information to prospective parents. The information provided encompasses prenatal care, intrapartum and postpartum care. Learning the genetic constitution of the parents pre-conception or the ongoing pregnancy allows parents to make decisions and set expectations. Offering screening and diagnostic testing has been the main in satisfying the desire for prenatal genetic information. With rapid advances in genomics and genome sequencing, screening during an ongoing pregnancy may become obsolete. Preconception risk will be determined by whole exome sequencing and chromosomal microarray of prospective parents and a number of approaches to alter pregnancy outcome can be considered when genome variations are identified. Therapeutic approaches include mitochondrial transfer and gene editing, two technologies that are in early stages, but showing promise as tools to alter outcomes. PMID- 28990983 TI - Pathology of Ovarian Cancer: Recent Insights Unveiling Opportunities in Prevention. AB - Ovarian carcinomas were formerly referred to as "surface epithelial carcinomas," reflecting the belief that they all arise from the ovarian surface epithelium. It is now appreciated that most ovarian carcinomas originate from either fallopian tube or endometriotic epithelium, and how we approach prevention will thus differ between histotypes. The 5 histotypes of ovarian carcinoma (high-grade serous, clear cell, endometrioid, mucinous, and low-grade serous, in descending order of frequency) can be reproducibly diagnosed, and are distinct disease entities, differing with respect to genetic risk factors, molecular events during oncogenesis, patterns of spread, and response to chemotherapy. PMID- 28990984 TI - Quality and Safety in Obstetrics and Gynecology. AB - The discipline of obstetrics and gynecology has been a leader for quality and safety in women's health for decades. Obstetrics is the leading cause for admissions, triage, and hospital discharge with over 4 million hospitalizations for births annually. Appropriately, safety initiatives and use of quality measures particularly relevant to obstetrics and gynecology are essential to patient satisfaction, safe and efficient evidence-based care. PMID- 28990985 TI - Endometriosis-associated Ovarian Cancers. AB - Endometriosis-associated cancers include clear cell and endometrioid ovarian carcinoma. A history of endometriosis has long been considered to be a risk factor for later development of these malignancies; however, recent molecular genetic evidence has provided unequivocal evidence that these lesions are in fact the precursors for endometriosis-associated cancers. Herein, we will explore the relationship between endometriosis and ovarian carcinomas, similarities between the premalignant lesions and their cancerous counterparts, and the potential role of mutations and the ovarian microenvironment that may contribute to malignant transformation. PMID- 28990986 TI - The Role of Hereditary Factors in Ovarian Carcinoma. AB - Cancer is a disease of the genome, in which mutations in particular genes and pathways give rise to tissue-specific genotype-phenotype correlations. In tumors associated with hereditary cancer syndromes, a person is generally born with the first mutation relevant to the development of their cancer. In this chapter we will discuss the genes that have been associated with germline mutations that confer a moderate to high risk for ovarian carcinoma. PMID- 28990987 TI - Standardization according to blood pressure lowering in meta-analyses of antihypertensive trials: comparison of three methodological approaches. AB - OBJECTIVE: Assess how standardization of relative risks (RRs) and standard errors (SEs), according to blood pressure differences within trials, affects heterogeneity, overall effect estimates and study weights in meta-analyses of antihypertensive treatment. METHOD: Data from a previous systematic review were used. Three sets of analyses were performed, using both random-effects and fixed effects model for meta-analyses. First, we used raw data from the included trials. Second, we standardized RRs as if SBP was reduced by 10 mmHg in all trials. Third, we standardized both RRs and SEs. RESULTS: When RRs were standardized according to blood pressure lowering, heterogeneity between trials increased (I(2) = 36 vs. 93% for mortality). This conferred large differences in treatment effect estimates using random-effects and fixed-effects model (RR 0.79, 95% confidence interval 0.70-0.89, respectively, 0.97, 0.94-0.99). When SEs were standardized, confidence intervals for individual trials widened, resulting in lower power to detect heterogeneity across trials. Study weights were dissociated from number of events in trials (P < 0.0001, R(2) = 0.99 before standardization vs. P = 0.063, R(2) = 0.05 after standardization). This induced a secondary shift in weight from trials with lower baseline SBP to trials with higher baseline SBP, resulting in exaggerated overall effect estimates. CONCLUSION: Standardization of RRs exaggerates differences between trials and makes meta-analyses highly sensitive to choice of statistical method. Standardization of SEs masks heterogeneity and results in biased effect estimates. PMID- 28990988 TI - Case Report: In Vivo Confocal Microscopic Appearance of Corneal Argyrosis. AB - SIGNIFICANCE: This report details the natural history of corneal argyrosis over 3 years using in vivo confocal microscopy to document regression of hyperreflective deposits, as well as effects on corneal nerves and endothelial cell morphology. PURPOSE: To report the in vivo confocal microscopic features and clinical characteristics of a case of bilateral corneal argyrosis. CASE REPORT: A 52-year old man referred to us 3 months following cautery of the palpebral conjunctiva of both eyes with a silver nitrate stick was observed over the course of 3 years, during which slit-lamp photography and in vivo confocal microscopy were performed. At the first visit, slit-lamp examination showed a light blue-green discoloration and a thick, yellow, oval discoloration in the right and left cornea, respectively. One year later, under slit-lamp examination, the right cornea appeared nearly transparent, and the discoloration in the left cornea had remarkably regressed. In vivo confocal microscopy done at that time showed highly reflective deposits in Descemet membrane of the right cornea and throughout Bowman layer, the stroma, and Descemet membrane of the left cornea. Three years later, no accumulation of silver was observed during slit-lamp examination of either eye. In vivo confocal microscopy of the right cornea did not reveal any silver deposits, and the corneal structure appeared normal. In the left cornea, some silver deposits were still evident in Descemet membrane, and alterations of corneal nerve and endothelial cell morphology were also evident. CONCLUSIONS: This report reviews the 3-year natural history of a patient with corneal argyrosis. In vivo confocal microscopy demonstrates that over time the corneal argyrosis gradually resolves without any treatment. However, the presence of silver in the cornea may impact the corneal nerves and endothelial cells. PMID- 28990989 TI - Enhancing Care of Aged and Dying Prisoners: Is e-Learning a Feasible Approach? AB - BACKGROUND: Prisons and jails are facing sharply increased demands in caring for aged and dying inmates. Our Toolkit for Enhancing End-of-life Care in Prisons effectively addressed end-of-life (EOL) care; however, geriatric content was limited, and the product was not formatted for broad dissemination. Prior research adapted best practices in EOL care and aging; but, delivery methods lacked emerging technology-focused learning and interactivity. PURPOSES: Our purposes were to uncover current training approaches and preferences and to ascertain the technological capacity of correctional settings to deliver computer based and other e-learning training. METHODS: An environmental scan was conducted with 11 participants from U.S. prisons and jails to ensure proper fit, in terms of content and technology capacity, between an envisioned computer-based training product and correctional settings. RESULTS: Environmental scan findings focused on content of training, desirable qualities of training, prominence of "homegrown" products, and feasibility of commercial e-learning. CONCLUSIONS/IMPLICATIONS: This study identified qualities of training programs to adopt and pitfalls to avoid and revealed technology-related issues to be mindful of when designing computer-based training for correctional settings, and participants spontaneously expressed an interest in geriatrics and EOL training using this learning modality as long as training allowed for tailoring of materials. PMID- 28990990 TI - How 6 Organizations Developed Tools and Processes for Social Determinants of Health Screening in Primary Care: An Overview. AB - Little is known about how health care organizations are developing tools for identifying/addressing patients' social determinants of health (SDH). We describe the processes recently used by 6 organizations to develop SDH screening tools for ambulatory care and the barriers they faced during those efforts. Common processes included reviewing literature and consulting primary care staff. The organizations prioritized avoiding redundant data collection, integrating SDH screening into existing workflows, and addressing diverse clinic needs. This article provides suggestions for others hoping to develop similar tools/strategies for identifying patients' SDH needs in ambulatory care settings, with recommendations for further research. PMID- 28990991 TI - Brazilian Payment for Performance (PMAQ) Seen From a Global Health and Public Policy Perspective: What Does It Mean for Research and Policy? AB - This supplement of the Journal of Ambulatory Care Management on the Brazilian National Program for Improving Access and Quality of Primary Care (PMAQ) reveals a relevant gap in the Brazilian literature on pay for performance/PMAQ, and is therefore an opportunity to bring contributions from global health and public policy to the debate. We discuss the relevant gap in the light of developments in evaluation and policy analysis. We afterward present the state of knowledge regarding global health and public policy in pay for performance, giving attention to diverse themes, methods, types of analyses, theoretical contributions, and limitations. Finally, we suggest some possible implications for research and policy in Brazil. PMID- 28990992 TI - Comparing Patient-Centered Medical Home Implementation in Urban and Rural VHA Clinics: Results From the Patient Aligned Care Team Initiative. AB - Rural Veterans Health Administration (VHA) primary care clinics are smaller, have fewer staff, and serve more rural patients compared with urban VHA primary care clinics. This may lead to different challenges to implementation of the Patient Centered Medical Home (PCMH) model, the Patient Aligned Care Team, in the VHAs' large integrated health system. In this cross-sectional observational study of 905 VHA primary clinics in the United States and Puerto Rico, we found overall PCMH implementation was greater in rural compared to urban primary care clinics. Urban-rural differences in PCMH implementation may largely be related to clinic organizational factors. PMID- 28990993 TI - Rural Patients' and Primary Care Clinic Staffs' Perceptions of EHR Implementation: An Ethnographic Exploration. AB - This focused ethnographic research study explores patients' and clinic staffs' experience of electronic health record (EHR) implementation in a small, independent, rural primary care practice. On the basis of participant observation of clinic staff, staff focus group, and patient interviews, results demonstrate that both patients and clinic staff have distrust and disconnect from technology. Yet, patients and clinic staff embrace patient-centered approaches and value team based care. Understanding patients' and staffs' experience can facilitate the EHR implementation in the rural primary care setting and facilitate online access, patient portals, and other technologically based patient-centered approaches. PMID- 28990994 TI - Long-Term Visual Outcomes, Complications, and Retention of the Boston Type I Keratoprosthesis. AB - PURPOSE: To report the long-term outcomes of the Boston type I keratoprosthesis (KPro). METHODS: Data were collected regarding preoperative characteristics, surgical procedure(s) performed, and postoperative outcomes of patients who underwent KPro implantation from May 1, 2004, to May 1, 2011, and were followed for 5 years after surgery. RESULTS: Seventy-four KPro procedures were performed in 58 eyes (55 patients), with more than 1 KPro implanted in 10 eyes. The mean follow-up duration was 82.8 +/- 20.5 months (range 57-145 months), and the most common indication for keratoprosthesis implantation was corneal transplant failure (50%). Preoperative corrected distance visual acuity (CDVA) was >=20/200 in 5%; between 1 and 8 years after surgery, the percentage of eyes with CDVA >=20/200 varied between 57% (4 years) and 82% (8 years). Nineteen (25.7%) KPros implanted were removed (retention failure rate 0.047/eye-year), although a KPro was retained at final follow-up in 55 eyes (94.8%). The most common postoperative complication was retroprosthetic membrane formation in 51.7% of eyes. The incidence of each postoperative complication decreased significantly over the first 10 years after surgery. CONCLUSIONS: The KPro provides significant visual improvement in most eyes, with more than 50% regaining and maintaining 20/200 CDVA each year through 8 years after surgery. The incidence of each postoperative complication decreases significantly over the first 10 years after surgery. Although almost one-quarter of implanted keratoprostheses were removed, over 90% of eyes reaching 5 years of follow-up retain a keratoprosthesis at final follow up. PMID- 28990995 TI - Donor Tissue Preparation for Descemet Membrane Endothelial Keratoplasty: An Updated Review. AB - PURPOSE: To provide an overview of the current literature on donor tissue preparation for Descemet membrane endothelial keratoplasty (DMEK). METHODS: A comprehensive database search without date restrictions was performed in PubMed and in The Cochrane Library in May, 2017. Keywords included Descemet membrane endothelial keratoplasty, corneal transplantation, graft, harvest, dissection, preparation, endothelial cell, and endothelial cell density. Articles aiming to describe or evaluate a technique for DMEK graft preparation were considered eligible and were included in this review. RESULTS: A graft dissection technique that provides consistent tissue qualities and a low risk of preparation failure is essential for surgeons and eye banks preparing DMEK tissue. Various techniques have been described aiming to facilitate DMEK graft dissection, including manual dissection, pneumatic dissection, and hydrodissection. All show a trend toward a no-touch technique, for example, without direct physical tissue manipulation during tissue harvesting, as a potential ideal approach to minimize graft damage. CONCLUSIONS: An overview of the current harvesting techniques available for DMEK may benefit corneal surgeons and eye banks in choosing the best approach for each specific user. PMID- 28990996 TI - Subbasal Nerve Plexus Changes in Chronic Migraine. AB - PURPOSE: Migraine is a multifactorial disorder that presents with unilateral headache and several sensory symptoms. Photophobia is one of the ophthalmic manifestations that cause significant morbidity. The trigeminal pathway that innervates the cornea in the form of afferents has been implicated in photophobia associated with chronic migraine. This study investigates changes in the corneal subbasal nerve plexus (SBNP) in chronic migraine patients with and without photophobia. METHODS: Thirty-six patients with migraine and photophobia (group 1), 24 patients with migraine without photophobia (group 2), and 24 age- and sex matched controls (group 3) were studied. A detailed history analysis and ophthalmic evaluation were performed on all subjects. In vivo confocal microscopy (IVCM) with automated CCMetrics software was used to quantify changes in the SBNP in all 3 groups. Measured parameters were compared using analysis of variance. RESULTS: Analysis of corneal SBNP features revealed a significant decrease in the corneal nerve fiber length (14.76 +/- 3.98 mm/mm), total branch density (43.37 +/ 21.63 branch points/mm), nerve branch density (30.19 +/- 15.76 number of branches/mm), and fiber area (0.005 +/- 0.001 total nerve fiber area/mm) in patients of group 1 compared with group 2 (P < 0.05). CONCLUSIONS: Structural changes in nociceptive corneal axons in the SBNP of patients with migraine with photophobia lend further support to the hypothesis that the trigeminal system plays a critical role in the pathogenesis of ocular symptoms in migraine. Our observations demonstrate that SBNP changes on IVCM may serve as a potential imaging marker for ocular symptoms of chronic migraine, and this warrants further investigation. PMID- 28990997 TI - Penetrating Keratoplasty at a Tertiary Referral Center in Ethiopia: Indications and Outcomes. PMID- 28990998 TI - Intermediate-Term and Long-Term Outcomes With the Boston Type 1 Keratoprosthesis in Aniridia. AB - PURPOSE: To report the intermediate- and long-term visual outcomes and complications with the Boston type 1 keratoprosthesis (KPro) for the management of aniridic keratopathy. METHODS: A retrospective chart review of 46 eyes of 34 patients (20 females and 14 males) with aniridic keratopathy who underwent Boston type 1 KPro surgery by a single surgeon from 2004 to 2012 with minimum 2-year follow-up was conducted. Preoperative, intraoperative, and postoperative parameters were collected and analyzed. The primary outcome was the change in best-corrected visual acuity. Secondary outcomes included the rate of retroprosthetic membrane formation, glaucoma progression, glaucoma tube revisions, and KPro retention. RESULTS: Mean age of the patients was 43.5 +/- 19.8 years with a mean follow-up period of 4.5 +/- 1.6 years (range 2-7.4 years). Thirty-four eyes (74%) had previously failed keratoplasty. Thirty-five eyes (76%) previously underwent ocular surface stem cell transplantation, specifically a keratolimbal allograft. Within the first 6 months postoperatively, 74% (34/46) of patients experienced a gain of >=2 lines of vision. Overall, there was a gain of >=2 lines of vision in 43.5% (20/46) of patients at last follow-up. The rate of retroprosthetic membrane formation was 61%, the rate of glaucoma onset/progression was 26%, the rate of tube revision was 31%, and the KPro retention rate was 87%. CONCLUSIONS: This study confirms that initial visual improvement in aniridic keratopathy cases occurs at a high rate with the Boston type 1 KPro but also found progressive loss of these initial visual improvements. PMID- 28991000 TI - Reply. PMID- 28990999 TI - Reply. PMID- 28991001 TI - Using Super Learner Prediction Modeling to Improve High-dimensional Propensity Score Estimation. AB - The high-dimensional propensity score is a semiautomated variable selection algorithm that can supplement expert knowledge to improve confounding control in nonexperimental medical studies utilizing electronic healthcare databases. Although the algorithm can be used to generate hundreds of patient-level variables and rank them by their potential confounding impact, it remains unclear how to select the optimal number of variables for adjustment. We used plasmode simulations based on empirical data to discuss and evaluate data-adaptive approaches for variable selection and prediction modeling that can be combined with the high-dimensional propensity score to improve confounding control in large healthcare databases. We considered approaches that combine the high dimensional propensity score with Super Learner prediction modeling, a scalable version of collaborative targeted maximum-likelihood estimation, and penalized regression. We evaluated performance using bias and mean squared error (MSE) in effect estimates. Results showed that the high-dimensional propensity score can be sensitive to the number of variables included for adjustment and that severe overfitting of the propensity score model can negatively impact the properties of effect estimates. Combining the high-dimensional propensity score with Super Learner was the most consistent strategy, in terms of reducing bias and MSE in the effect estimates, and may be promising for semiautomated data-adaptive propensity score estimation in high-dimensional covariate datasets. PMID- 28991002 TI - Estimating the Effect of Preventable Treatment Discontinuation on Health Outcomes. AB - BACKGROUND: There is increased interest in studying the effects of medication adherence on health outcomes. However, if patients appropriately stop treatment because of side effects and treatment failure, it is neither possible nor clinically meaningful to estimate the effect of full medication adherence. METHODS: We present an analysis designed to estimate the effect of nonmedical (preventable) discontinuation of cinacalcet, an oral medication approved to treat secondary hyperparathyroidism in patients with end-stage renal disease on dialysis on mortality and heart failure. The approach involves artificially censoring patients who discontinue treatment for a reason that does not appear to be related to an adverse effect of treatment. We address potential bias from informative censoring through inverse-probability of censoring weighted estimation. RESULTS: Although the analysis is subject to possible residual confounding by the healthy adherer effect and other limitations, we find that potentially preventable discontinuation associates with 2.9 excess deaths at 1 year per 100 patients treated (95% confidence interval, 2.4, 3.5), and 4.6 excess deaths at 2 years (95% confidence interval, 3.5, 5.5). The association between cinacalcet persistence and heart failure hospitalization risk was sensitive to the outcome definition. CONCLUSIONS: Inverse-probability of censoring weighted estimation can be used to estimate the effect of potentially preventable treatment discontinuation in populations where treatment can be stopped for both medical and nonmedical reasons. Estimates from such approaches may represent an upper bound of what would be achievable by an adherence improvement intervention. PMID- 28991004 TI - Erratum. PMID- 28991003 TI - Site-specific Solid Cancer Mortality After Exposure to Ionizing Radiation: A Cohort Study of Workers (INWORKS). AB - BACKGROUND: There is considerable scientific interest in associations between protracted low-dose exposure to ionizing radiation and the occurrence of specific types of cancer. METHODS: Associations between ionizing radiation and site specific solid cancer mortality were examined among 308,297 nuclear workers employed in France, the United Kingdom, and the United States. Workers were monitored for external radiation exposure and follow-up encompassed 8.2 million person-years. Radiation-mortality associations were estimated using a maximum likelihood method and using a Markov chain Monte Carlo method, the latter used to fit a hierarchical regression model to stabilize estimates of association. RESULTS: The analysis included 17,957 deaths attributable to solid cancer, the most common being lung, prostate, and colon cancer. Using a maximum-likelihood method to quantify associations between radiation dose- and site-specific cancer, we obtained positive point estimates for oral, esophagus, stomach, colon, rectum, pancreas, peritoneum, larynx, lung, pleura, bone and connective tissue, skin, ovary, testis, and thyroid cancer; in addition, we obtained negative point estimates for cancer of the liver and gallbladder, prostate, bladder, kidney, and brain. Most of these estimated coefficients exhibited substantial imprecision. Employing a hierarchical model for stabilization had little impact on the estimated associations for the most commonly observed outcomes, but for less frequent cancer types, the stabilized estimates tended to take less extreme values and have greater precision than estimates obtained without such stabilization. CONCLUSIONS: The results provide further evidence regarding associations between low-dose radiation exposure and cancer. PMID- 28991007 TI - The optimal approach to nutrition and cystic fibrosis: latest evidence and recommendations. AB - PURPOSE OF REVIEW: Cystic fibrosis (CF) is a progressive genetic disease that affects multiple organ systems. Therapy is directed to maintain and optimize nutritional status and pulmonary function, as these are key factors in survival. In this review, the most recent findings regarding nutritional management associated with pulmonary function and outcome will be explored. RECENT FINDINGS: Evidence-based and expert-based guidelines emphasize the need for adequate nutritional intake to improve nutritional status. For infants and young children, the aim is to achieve the 50th percentile of weight and length for a healthy same age population up to age 2 years. For older children and adolescents 2-18 years, the target is a BMI of at or above the 50th percentile for healthy children. For CF adults of at least 18 years, the target is a BMI of at or above 22 kg/m for women and at or above 23 kg/m for men. Recently, new drugs are developed with the aim to treat the malfunction of the cystic fibrosis transmembrane conductance regulator gene. This potentiator/corrector therapy improves lung function and nutritional status and decreases the number of infective exacerbations. As survival is improving and the CF population is aging, it is important to focus on micronutrient and macronutrient intake of CF patients in different age and disease stages. SUMMARY: Recent evidence-based nutritional guidelines and improved medical treatment support the nutritional monitoring and interventions in CF patients. Nutritional care should be personalized and provided by a specialized CF dietitian because patients' care needs may change dramatically during their disease progress. PMID- 28991006 TI - Autoimmunity in narcolepsy. AB - PURPOSE OF REVIEW: Summarize the recent findings in narcolepsy focusing on the environmental and genetic risk factors in disease development. RECENT FINDINGS: Both genetic and epidemiological evidence point towards an autoimmune mechanism in the destruction of orexin/hypocretin neurons. Recent studies suggest both humoral and cellular immune responses in the disease development. SUMMARY: Narcolepsy is a severe sleep disorder, in which neurons producing orexin/hypocretin in the hypothalamus are destroyed. The core symptoms of narcolepsy are debilitating, extreme sleepiness, cataplexy, and abnormalities in the structure of sleep. Both genetic and epidemiological evidence point towards an autoimmune mechanism in the destruction of orexin/hypocretin neurons. Importantly, the highest environmental risk is seen with influenza-A infection and immunization. However, how the cells are destroyed is currently unknown. In this review we summarize the disease symptoms, and focus on the immunological findings in narcolepsy. We also discuss the environmental and genetic risk factors as well as propose a model for disease development. PMID- 28991008 TI - NACNS Newsletter: President's Message. PMID- 28991009 TI - What Caregivers Need From Clinical Nurse Specialists. PMID- 28991010 TI - Improving Triage: The Essential Information to Compare Different Approaches. PMID- 28991011 TI - Creating a Credible and Ethical Curriculum Vitae. PMID- 28991012 TI - "Gray Death"-The Trojan Horse of the Opioid Epidemic: Historical, Clinical, and Safety Evidence for the Clinical Nurse Specialist. PMID- 28991013 TI - Leadership in Nursing: The Importance of Influence. PMID- 28991014 TI - Opportunities for the Advanced Practice Nurse to Enhance Hypertension Knowledge and Self-management Among African American Women. AB - PURPOSE: Despite increased awareness and the advent of methods to manage the disease, hypertension is poorly controlled among African American women. This study explored hypertension knowledge and blood pressure in a sample of African American women. DESIGN: A descriptive, cross-sectional design was used to collect survey data on hypertension knowledge. METHODS: African American women attending a church conference were invited to complete a questionnaire, which included the Check Your High Blood Pressure Prevention IQ survey, and had their blood pressures measured. RESULTS: Of the 151 women who participated, 62% were diagnosed with hypertension. Many of the women, even those not diagnosed with hypertension, had elevated blood pressures. Although the average scores showed that the women scored well on the survey, there were 4 items on the survey that a percentage of the women had difficulty with: questions about (1) stress as a cause of hypertension, (2) symptoms associated with high blood pressure, (3) whether hypertension could be cured, and (4) the amount of exercise needed to help reduce blood pressure. CONCLUSION: Despite efforts to increase awareness and control of hypertension, considerable misconceptions about the disease were found in this sample of African American women. To improve self-management of hypertension among this group, advanced practice nurses need to directly address these misconceptions. PMID- 28991016 TI - Process of Transition for Congenital Heart Patients: Preventing Loss to Follow up. AB - PURPOSE: The aim of this article is to provide an overview of our nurse-led transition clinic provided to congenital heart disease patients moving from pediatric into adult care setting. DESCRIPTION OF THE SERVICE: Nurse-led transition clinic was analyzed at various stages of young adult care from an early stage of 12 to 14 years to entering adult setting at 16 years or older. METHODS: Overview of current transition service for young adults being transferred from pediatric into adult services highlights the integral role of clinical nurse specialist as a coordinator of care. RESULTS: The result of the service overview indicates that nurse-led transition service enables patients to build on their knowledge. This is achieved by providing them time and the opportunities to develop an understanding of their condition and the attitudes required to engage with the adult care setting as indicated in the psychology questionnaire from transition day. CONCLUSION: A nurse-led transition clinic enhances long-term care of patients by supporting the young adults and their family/carer through the transition and transfer of the care to promote the young adult's understanding of their condition and to prevent any lost to follow-up. PMID- 28991015 TI - Enhancing Outcomes for Outpatient Percutaneous Coronary Interventions. AB - PURPOSE AND OBJECTIVES: A quality improvement project was conducted to create a sustainable continuum of care for increased volumes of outpatients receiving percutaneous coronary interventions. Dramatic growth exposed system vulnerabilities and left staff overwhelmed. Four postinterventional project objectives included reducing preprocedural preparation times, reducing bleeding complications, reducing hospital length of stay, and collectively increasing patient satisfaction. DESCRIPTION OF THE PROJECT: Amidst creating a specialized postintervention coronary recovery area and acquiring and training existing preregistration and recovery nurses, a fragmented system of care was united. The clinical nurse specialist-led project used a systematic and evidence-based implementation process to harmoniously acclimate perioperative staff. An evaluation process further defined new opportunities to support a growing service line. OUTCOMES: Postimplementation data were collected over a 3-month period. An overall improvement was found in all targeted objectives, despite an upsurge in case volumes. A moderately significant correlation (r [105] = 0.424, P < .001) was found between bleeding occurrences and hospital length of stay. CONCLUSION: The synergy between interdepartmental collaboration and strategic staffing reallocation was shown to be invaluable to alleviate procedural areas of service, such as the cardiac catheterization laboratory. As a project champion, the clinical nurse specialist is an essential catalyst to identify and creatively surmount system-level challenges. PMID- 28991017 TI - Transitioning Into Practice: Reflections and Advice for the New Clinical Nurse Specialist. AB - PURPOSE/OBJECTIVES: The purposes of this article are to explore the shared experiences and feelings of clinical nurse specialists (CNSs) who were new to the role and to identify strategies that were helpful in making the transition. DESCRIPTION OF PROJECT/PROGRAM: Transitioning to a CNS role may be challenging and emotional, causing fear or anxiety. The authors reflected on their experiences of transitioning into CNS practice. OUTCOME: Reflection on the literature led to advice and helpful strategies for new CNSs as they transition into practice. CONCLUSION: The strategies identified can be used to develop a structured orientation that may ease the transition into the CNS role. PMID- 28991018 TI - Clinical Nurse Specialist-Driven Practice Change: Standardizing Vital Sign Monitoring. AB - PURPOSE: The purpose of this project was to standardize vital sign (VS) monitoring throughout a patient's stay in the hospital, including at admission, following transitions to different levels of care, reassessment of abnormal VS results, daily monitoring, and before dismissal. The population of focus was adult general and progressive care patients. DESCRIPTION OF THE PROJECT: Standards for VS monitoring, documentation, and provider notification were established. Unit routines, nursing procedural guidelines, and order sets were updated with the new standards. Nursing staff received Web-based education. Compliance with the new standards was monitored monthly, and data were shared with nursing leadership. Leadership reviewed the data with nursing staff to identify opportunities and recognize achievements. OUTCOMES: Overall, improvement in VS documentation was achieved. Continued opportunities exist for monitoring and reassessment of a full set of VSs after an abnormal result. CONCLUSION: Establishing a minimum standard of VS frequency and documentation allows for all healthcare providers to trend and monitor a patient's clinical status. Variability in patient care can be diminished by establishing minimum standards of VS monitoring. PMID- 28991019 TI - Using Twitter to Teach Evidence-Based Practice in Doctor of Nursing Practice Degree Program. PMID- 28991020 TI - Reflections on an Ancient Islamic Myth: Herbert Mason?'s Poem "Finch". PMID- 28991022 TI - "Gray Death" - The Trojan Horse of the Opioid Epidemic: Historical, Clinical, and Safety Evidence for the Clinical Nurse Specialist. PMID- 28991021 TI - Reliability and Validity of the Turkish Version of the Moral Competence Scale for Public Health Nurses: A Methodological Study. AB - BACKGROUND: Moral competencies must be improved in nursing area practice. To evaluate the moral competence seems necessary for nurses. AIM: The aims of this study are to adapt and evaluate the psychometric properties of the moral competence questionnaire for public health nurses in Turkey. METHOD: The moral competence scale was translated into Turkish by a skilled translator, after which it was back-translated into English by another translator. We then administered the Turkish version of the moral competence scale to 138 public health nurses working in family and public health centers in Erzurum, a city in eastern Turkey. We analyzed the data using factor analysis and Cronbach's alpha. RESULTS: Three factors were extracted, which together explained a total of 67.50% of the variance. The Cronbach's alpha values were .83, .91, .87, and .88 for factors 1, 2, and 3 and for the whole scale, respectively. CONCLUSION: The Turkish version of the moral competence scale for public health nurses is a valid and reliable assessment tool. PMID- 28991024 TI - Pretreatment integrase strand transfer inhibitor resistance in North Carolina from 2010-2016. AB - OBJECTIVE: We sought to define the prevalence of pretreatment integrase strand transfer inhibitor (INSTI) resistance and assess the transmission networks of those with pretreatment INSTI resistance. DESIGN: A retrospective cohort study of HIV-positive patients with genotypic resistance testing sent to a single referral laboratory in North Carolina between 2010 and 2016. METHODS: We linked genotype and public health data for in-care HIV-positive individuals to determine the prevalence of INSTI resistance among treatment-naive (defined as those with a first genotype <=3 months after diagnosis) and treatment-experienced (defined as those with a first genotype >3 months after diagnosis) patients. We performed molecular and phylogenetic analyses to assess whether pretreatment INSTI resistance mutations represented clustered HIV transmission. RESULTS: Of 8825 individuals who contributed sequences for protease, reverse transcriptase, or INSTI genotypic resistance testing during the study period, 2784 (31%) contributed at least one sequence for INSTI resistance testing. Of these, 840 were treatment-naive individuals and 20 [2.4%, 95% confidence interval (CI): 1.5, 3.6%] had INSTI mutations; only two (0.2%, 95% CI: 0.02, 0.9%) had major mutations. Of 1944 treatment-experienced individuals, 9.6% (95% CI: 8.3, 11.0%) had any INSTI mutation and 7.0% (95% CI: 5.9, 8.3%) had major mutations; the prevalence of INSTI mutations among treatment-experienced patients decreased overtime (P < 0.001). In total 12 of 20 individuals with pretreatment INSTI mutations were part of 10 molecular transmission clusters; only one cluster shared identical minor mutations. CONCLUSION: The prevalence of major pretreatment INSTI resistance is very low. Pretreatment INSTI mutations do not appear to represent clustered HIV transmission. PMID- 28991023 TI - Pre-exposure prophylaxis for MSM and transgender persons in early adopting countries. AB - : Pre-exposure prophylaxis (PrEP) is a potent and underutilized HIV prevention tool. In this paper we review the state of knowledge regarding PrEP implementation for men who have sex with men and transgender persons in early adopting countries. We focus on implementation of PrEP in demonstration projects and clinical care, and describe the status of PrEP availability and uptake. We report on approaches to identifying appropriate PrEP candidates in real-world settings and on best practices for clinical monitoring. This includes the exclusion of undiagnosed HIV infection prior to PrEP initiation and longitudinal measurement of renal function, in light of safety data. Since adherence is the primary factor moderating the effectiveness of PrEP, we discuss effective adherence support interventions. Additionally, we review the evidence for risk compensation with PrEP use and opportunities to provide PrEP as part of comprehensive and inclusive preventive health programs. We summarize cost effectiveness studies, including their variable conclusions because of differing underlying assumptions, and discuss the importance of budgetary impact for public health programs and health care insurers. Further, we emphasize a need for greater engagement of health care providers in PrEP to increase access. We conclude with recommendations for ways to improve future efforts at implementing PrEP. PMID- 28991025 TI - The costs of HIV treatment and care in Ghana. AB - OBJECTIVE: To determine cost functions that describe the dynamics of costs of HIV treatment and care in Ghana by CD4 cell count at treatment initiation and over time on antiretroviral therapy (ART). DESIGN: We used detailed longitudinal healthcare utilization data from clinical health records of HIV-infected patients at seven Ghanaian ART clinics to estimate cost functions of treatment and care by CD4 cell count at treatment initiation and time on ART. METHODS: We developed two linear regression models; one with individual random effects to determine the relationship between CD4 cell count at ART initiation and costs of treatment and care, and one with individual fixed effects to determine the causal effect of time in care on costs of treatment and care. RESULTS: Costs for treatment and care were lowest (-7.9 US$) for patients with CD4 cell counts of at least 350 cells/MUl at ART initiation, compared with patients with 50 cells/MUl or less at ART initiation, yet the difference was not significant. The per-patient costs peaked during the first 6 months on ART at 112.6 US$, and significantly decreased by 70% after 4 years on treatment. CONCLUSION: Our findings show that an accurate analysis of resource needs of HIV treatment and care should take into account that healthcare costs for HIV-infected people are dynamic rather than constant. The cost functions derived from our study are valuable input for cost effectiveness analyses and research allocation exercises for HIV treatment in sub Saharan Africa. PMID- 28991028 TI - Predictive value of galectin-1 in the development and progression of HIV associated lymphoma. PMID- 28991029 TI - Successful treatment with tenofovir alafenamide of a HIV/hepatitis B virus coinfected patient with HIV and hepatitis B virus drug resistance, end-stage renal disease on haemodialysis. PMID- 28991026 TI - Frailty is strongly associated with increased risk of recurrent falls among older HIV-infected adults. AB - OBJECTIVE: Both frailty and falls occur at earlier-than-expected ages among HIV infected individuals, but the contribution of frailty-to-fall risk in this population is not well understood. We examined this association among participants enrolled in AIDS Clinical Trials Group (ACTG) A5322. DESIGN: A prospective, multicenter cohort study of HIV-infected men and women aged at least 40 years. METHODS: Frailty assessment included a 4-m walk, grip strength, and self-reported weight loss, exhaustion, and low physical activity. Multinomial logistic regression assessed the association between baseline frailty, grip, and 4-m walk, and single and recurrent (2+) falls over the next 12 months; logistic regression assessed effect modification by several factors on association between frailty and any (1+) falls. RESULTS: Of 967 individuals, 6% were frail, 39% prefrail, and 55% nonfrail. Eighteen percent had at least one fall, and 7% had recurrent falls. In multivariable models, recurrent falls were more likely among frail (odds ratio 17.3, 95% confidence interval 7.03-42.6) and prefrail (odds ratio 3.80, 95% CI 1.87-7.72) than nonfrail individuals. Significant associations were also seen with recurrent falls and slow walk and weak grip. The association between frailty and any falls was substantially stronger among individuals with peripheral neuropathy. CONCLUSION: Aging HIV-infected prefrail and frail individuals are at significantly increased risk of falls. Incorporation of frailty assessments or simple evaluations of walk speed or grip strength in clinical care may help identify individuals at greatest risk for falls. Peripheral neuropathy further increases fall risk among frail persons, defining a potential target population for closer fall surveillance, prevention, and treatment. PMID- 28991027 TI - Risk factors for anal high-grade squamous intraepithelial lesions in HIV-positive MSM: is targeted screening possible? AB - OBJECTIVE: HIV-positive MSM are at increased risk for developing anal squamous cell carcinoma. Detection of precursor lesions of anal cancer [anal high-grade squamous intraepithelial lesions (HSIL)] is cumbersome and expensive. Our objective was to identify potential risk factors for anal HSIL in HIV-positive MSM to develop more stringent screening criteria. DESIGN: We studied a cohort of MSM screened by high-resolution anoscopy at three HIV clinics in Amsterdam, the Netherlands. METHODS: For every first high-resolution anoscopy performed in a patient, we analyzed five demographic and seven HIV-related potential risk factors for four different outcome measures: histologically proven anal HSIL vs. no squamous intraepithelial lesions (SIL), HSIL-anal intraepithelial neoplasia 2 vs. no SIL, HSIL-anal intraepithelial neoplasia 3 vs. no SIL, and HSIL vs. no HSIL. We used univariable and multilevel, multivariable logistic regression. RESULTS: From 2008 through 2015, 497 out of 1678 (30%) screened HIV-positive MSM had anal HSIL. The mean age was 49 years (SD 9.6), 96% used combination antiretroviral therapy, and median duration of combination antiretroviral therapy use was 7.8 years (interquartile range 4.0-12.4). Increasing age [adjusted odds ratio (aOR) 0.82, 95% confidence interval (CI) 0.70-0.94, P = 0.006] and years living with suppressed viral load [1-5 years suppressed aOR 0.52 (95% CI 0.34 0.80), 5.01-10 years aOR 0.47 (95% CI 0.29-0.74), >10 years aOR 0.54 [0.34-0.87], all compared to less than 1 year suppressed, P = 0.009] were found to be protective for HSIL vs. no SIL. CONCLUSION: Young HIV-positive MSM without viral suppression are statistically at highest risk for anal HSIL, but given the high prevalence among all virally suppressed men, we advise that all HIV-positive MSM should be screened for HSIL. PMID- 28991030 TI - Educational Model to Increase the Number and Diversity of RN to BSN Graduates From a Resource-Limited Rural Community. AB - Increasing the number of BSN-prepared nurses at the bedside is directly linked to improved health care outcomes. However, employers are challenged to find enough BSN graduates to meet workforce demands. This article presents an educational model that uses evidence-based practices to increase enrollment, retention, and graduation rates of RN students in a BSN program (RN-BSN) in a resource limited rural community. This exemplar may equip nurse educators with strategies to adopt in their own communities. PMID- 28991031 TI - An Innovative Exchange Model for Global and Community Health Nursing Education. AB - Understanding different cultures is important in the education of nursing students who will become the health care workforce of our future interdependent and globalized societies. International practicum courses help students and nurses understand different cultures. This article describes an innovative approach to nursing education and understanding diverse cultures, in the context of a hybrid course (online course coupled with face-to-face practicum experiences), which enrolled nursing students from opposite hemispheres. PMID- 28991032 TI - Comparison of Nursing Student and Instructor Preferences for Block and Nonblock Clinical Models. AB - Clinical experiences are the hallmark of prelicensure nursing programs and assist students with applying nursing theory into practice. The literature is limited with respect to nursing student and instructor preferences for type of clinical model to facilitate student learning. This article explores these perceptions in the nursing programs of 5 universities located in 4 Western Canadian provinces. Findings support the use of both nonblock and block clinical models throughout nursing education programs. PMID- 28991033 TI - Communication Simulation Using Laypersons as Standardized Patients: Preparing Students for Their First Clinical Day. PMID- 28991034 TI - A Retrospective Analysis of Nursing Students' Clinical Experience in an All-Male Maximum Security Prison. AB - Prisons provide an ideal learning experience to prepare prelicensure students with the knowledge and skill set needed for practice in the 21st century. Beginning descriptive evidence demonstrates that correctional health is an innovative community resource to educate nursing students in today's changing model of health care delivery and practice. This article shares results from a retrospective analysis of the perceptions and experiences of nursing students during their community clinical rotation in an all-male maximum security prison. PMID- 28991035 TI - Substance Use Disorder Among Nurses: A Curriculum Improvement Initiative. AB - Substance use disorder (SUD) among nurses is a serious practice issue that poses a significant risk to patients and nurses. However, the topic of SUD is inadequately addressed in nursing education. A comprehensive education strategy was implemented and evaluated in 2 prelicensure nursing programs to improve nursing students' knowledge, skills, and attitudes about SUD among nurses. PMID- 28991036 TI - No Effect of beta-alanine on Muscle Function and Kayak Performance. AB - PURPOSE: If beta-alanine supplementation counteracts muscular fatigue development or improves athletic performance was investigated. METHODS: Elite kayak rowers (10 men and 7 women) were supplemented with either 80 mg.kg body mass.d of beta alanine or placebo for 8 wk. Muscular fatigue development was investigated by applying a 2-min elbow flexor maximal voluntary contraction (MVC). EMG was recorded continuously, and voluntary activation was determined 30, 60, 90, and 115 s into the 2-min MVC. In addition, performance was evaluated as 1000-m and 5 * 250-m kayak ergometer rowing. RESULTS: Force reduction during the 2-min MVC was similar before and after supplementation with beta-alanine (30.9% +/- 10.3% vs 36.0% +/- 14.1%) and placebo (35.5% +/- 7.7% vs 35.1% +/- 8.0%). No time effect was apparent in voluntary activation during the 2-min MVC. In addition, there was no detectable effect of beta-alanine supplementation on 1000-m kayak ergometer performance (beta-alanine: 0.26% +/- 0.02% vs placebo: -0.18% +/- 0.02%) or accumulated 5 * 250-m time (beta-alanine: -1.0% +/- 0.3% vs placebo: -1.0% +/- 0.2%). In 5 * 250 m, mean power output was reduced to a similar extent from first to fifth interval before and after supplementation with beta-alanine (23% +/- 11% vs 22% +/- 10%) and placebo (26% +/- 13% vs 20% +/- 5%). CONCLUSIONS: Two-minute MVC characteristics are unaffected by beta-alanine supplementation in elite kayakers, and likewise, both a 1000-m kayak ergometer time trial lasting 4-5 min and a 5 * 250-m repeated sprint ability were unaltered by supplementation. PMID- 28991037 TI - Mechanisms of Fatigue and Recovery in Upper versus Lower Limbs in Men. AB - PURPOSE: To compare the mechanisms of fatigue and recovery between upper and lower limbs in the same subjects. METHODS: Twelve healthy young men performed a 2 min sustained maximal voluntary isometric contraction (MVC) of the knee extensors (KE) and on another day a 2-min MVC of the elbow flexors (EF). Neuromuscular function evaluations were performed with both transcranial magnetic and peripheral stimulations before (PRE), at the end of the 2-min MVC, and five more times within 8 min of recovery. RESULTS: Decreases in MVC and cortical voluntary activation were approximately 12% (P < 0.001) and approximately 25% greater (P = 0.04) in KE than EF at end of the 2-min MVC. Conversely, twitch response decreased approximately 29% more (P = 0.02) in EF than KE. Changes in motor evoked potential with fatigue were not different between upper and lower limbs (P > 0.05), whereas the increase in silent period duration was approximately 30% greater in EF than KE (P < 0.05). CONCLUSIONS: Upper and lower limbs presented different magnitudes of total, central and peripheral fatigue. Total neuromuscular fatigue and central fatigue were greater in KE than EF. Conversely, peripheral fatigue and corticospinal inhibition were greater in EF than KE. PMID- 28991038 TI - Exercise Prescription and Adherence for Breast Cancer: One Size Does Not FITT All. AB - PURPOSE: To prospectively assess adherence to oncologist-referred, exercise programming consistent with current recommendations for cancer survivors among women with early breast cancer across the trajectory of adjuvant treatment. METHODS: Sixty-eight women participated in supervised, hour-long, moderate intensity, aerobic, and resistance exercise thrice per week during adjuvant chemotherapy +/- radiation, with a step-down in frequency for 20 additional weeks. Adherence to exercise frequency (i.e., attendance), intensity, and time/duration, and barriers to adherence were tracked and compared during chemotherapy versus radiation, and during treatment (chemotherapy plus radiation, if received) versus after treatment. RESULTS: Attendance decreased with cumulative chemotherapy dose (cycles 1-2 vs cycles 3-8, cycle 3 vs cycles 7-8, all P <= 0.05) and was lower during chemotherapy than radiation (64% +/- 25% vs 71% +/- 32%, P = 0.02) and after treatment than during treatment (P < 0.01). Adherence to exercise intensity trended toward being higher during chemotherapy than radiation (69% +/- 23% vs 51% +/- 38%, P = 0.06) and was higher during than after treatment (P = 0.01). Adherence to duration did not differ with treatment. Overall adherence to the resistance prescription was poor, but was higher during chemotherapy than radiation (57% +/- 23% vs 34% +/- 39%, P < 0.01) and was not different during than after treatment. The most common barriers to attendance during treatment were cancer-related (e.g., symptoms, appointments), and after treatment were life-related (e.g., vacation, work). CONCLUSIONS: Adherence to supervised exercise delivered in a real-world clinical setting varies among breast cancer patients and across the treatment trajectory. Behavioral strategies and individualization in exercise prescriptions to improve adherence are especially important for later chemotherapy cycles, after treatment, and for resistance exercise. PMID- 28991039 TI - Heavy-Load Lifting: Acute Response in Breast Cancer Survivors at Risk for Lymphedema. AB - PURPOSE: Despite a paucity of evidence, prevention guidelines typically advise avoidance of heavy lifting in an effort to protect against breast cancer-related lymphedema. This study compared acute responses in arm swelling and related symptoms after low- and heavy-load resistance exercise among women at risk for lymphedema while receiving adjuvant taxane-based chemotherapy. METHODS: This is a randomized, crossover equivalence trial. Women receiving adjuvant taxane-based chemotherapy for breast cancer who had undergone axillary lymph node dissection (n = 21) participated in low-load (60%-65% 1-repetition maximum, two sets of 15 20 repetitions) and heavy-load (85%-90% 1-repetition maximum, three sets of 5-8 repetitions) upper-extremity resistance exercise separated by a 1-wk wash-out period. Swelling was determined by bioimpedance spectroscopy and dual-energy x ray absorptiometry, with breast cancer-related lymphedema symptoms (heaviness, swelling, pain, tightness) reported using a numeric rating scale (0-10). Order of low- versus heavy-load was randomized. All outcomes were assessed before, immediately after, and 24 and 72 h after exercise. Generalized estimating equations were used to evaluate changes over time between groups, with equivalence between resistance exercise loads determined using the principle of confidence interval inclusion. RESULTS: The acute response to resistance exercise was equivalent for all outcomes at all time points irrespective of loads lifted, with the exception of extracellular fluid at 72 h after exercise with less swelling after heavy loads (estimated mean difference, -1.00; 95% confidence interval, -3.17 to 1.17). CONCLUSIONS: Low- and heavy-load resistance exercise elicited similar acute responses in arm swelling and breast cancer-related lymphedema symptoms in women at risk for lymphedema receiving adjuvant taxane based chemotherapy. These represent important preliminary findings, which can be used to inform future prospective evaluation of the long-term effects of repeated exposure to heavy-load resistance exercise. PMID- 28991041 TI - Quadriceps Function and Knee Joint Ultrasonography after ACL Reconstruction. AB - PURPOSE: Individuals with anterior cruciate ligament reconstruction (ACLR) are at greater risk for knee osteoarthritis, partially because of chronic quadriceps dysfunction. Articular cartilage is commonly assessed using magnetic resonance imaging and radiography, but these methods are expensive and lack portability. Ultrasound imaging may provide a cost-effective and portable alternative for imaging the femoral cartilage. The purpose of this study was to compare ultrasonography of the femoral cartilage between the injured and uninjured limbs of individuals with unilateral ACLR, and to examine the association between quadriceps function and ultrasonographic measures of femoral cartilage. METHODS: Bilateral femoral cartilage thickness and quadriceps function were assessed in 44 individuals with unilateral ACLR. Quadriceps function was assessed using peak isometric strength, and early (RTD100) and late (RTD200) rate of torque development. RESULTS: Cartilage thickness at the medial femoral condyle (P < 0.001) and femoral cartilage cross-sectional area (P = 0.007) were smaller in the injured compared with the uninjured limb. After accounting for time since ACLR, quadriceps peak isometric strength was associated with cartilage thickness at the medial femoral condyle (r = 0.35, P = 0.02) and femoral cartilage cross-sectional area (r = 0.28, P = 0.04). RTD100 and RTD200 were not associated with femoral cartilage thickness or cross-sectional area. CONCLUSIONS: Individuals with ACLR have thinner cartilage in their injured limb compared with uninjured limb, and cartilage thickness is associated with quadriceps function. These results indicate that ultrasonography may be useful for monitoring cartilage health and osteoarthritis progression after ACLR. PMID- 28991040 TI - Associations of Muscle Mass and Strength with All-Cause Mortality among US Older Adults. AB - INTRODUCTION: Recent studies suggested that muscle mass and muscle strength may independently or synergistically affect aging-related health outcomes in older adults; however, prospective data on mortality in the general population are sparse. METHODS: We aimed to prospectively examine individual and joint associations of low muscle mass and low muscle strength with all-cause mortality in a nationally representative sample. This study included 4449 participants age 50 yr and older from the National Health and Nutrition Examination Survey 1999 to 2002 with public use 2011 linked mortality files. Weighted multivariable logistic regression models were adjusted for age, sex, race, body mass index (BMI), smoking, alcohol use, education, leisure time physical activity, sedentary time, and comorbid diseases. RESULTS: Overall, the prevalence of low muscle mass was 23.1% defined by appendicular lean mass (ALM) and 17.0% defined by ALM/BMI, and the prevalence of low muscle strength was 19.4%. In the joint analyses, all-cause mortality was significantly higher among individuals with low muscle strength, whether they had low muscle mass (odds ratio [OR], 2.03; 95% confidence interval [CI], 1.27-3.24 for ALM; OR, 2.53; 95% CI, 1.64-3.88 for ALM/BMI) or not (OR, 2.66; 95% CI, 1.53-4.62 for ALM; OR, 2.17; 95% CI, 1.29-3.64 for ALM/BMI). In addition, the significant associations between low muscle strength and all-cause mortality persisted across different levels of metabolic syndrome, sedentary time, and LTPA. CONCLUSIONS: Low muscle strength was independently associated with elevated risk of all-cause mortality, regardless of muscle mass, metabolic syndrome, sedentary time, or LTPA among US older adults, indicating the importance of muscle strength in predicting aging-related health outcomes in older adults. PMID- 28991042 TI - Maximum Skin Wettedness after Aerobic Training with and without Heat Acclimation. AB - PURPOSE: To quantify how maximum skin wettedness (omegamax); that is, the determinant of the boundary between compensable and uncompensable heat stress, is altered by aerobic training in previously unfit individuals and further augmented by heat acclimation. METHODS: Eight untrained individuals completed an 8-wk aerobic training program immediately followed by 8 d of hot/humid (38 degrees C, 65%RH) heat acclimation. Participants completed a humidity ramp protocol pretraining (PRE-TRN), posttraining (POST-TRN), and after heat acclimation (POST HA), involving treadmill marching at a heat production of 450 W for 105 min in 37.5 degrees C, 2.0 kPa (35%RH). After attaining a steady-state esophageal temperature (Tes), humidity increased 0.04 kPa.min. An upward inflection in Tes indicated the upper limit of physiological compensability (Pcrit), which was then used to quantify omegamax. Local sweat rate, activated sweat gland density, and sweat gland output on the back and arm were simultaneously measured throughout. RESULTS: Peak aerobic capacity increased POST-TRN by approximately 14% (PRE-TRN: 45.8 +/- 11.8 mL.kg.min; POST-TRN: 52.0 +/- 11.1 mL.kg.min, P < 0.001). omegamax values became progressively greater from PRE-TRN (0.72 +/- 0.06) to POST-TRN (0.84 +/- 0.08; P = 0.02), to POST-HA (0.95 +/- 0.05; P = 0.03). These shifts in omegamax were facilitated by a progressively greater local sweat rate and activated sweat gland density from PRE-TRN (0.84 +/- 0.21 mg.cm.min; 67 +/- 20 glands per square centimeter) to POST-TRN (0.96 +/- 0.21 mg.cm.min, P = 0.03; 86 +/- 27 glands per square centimeter; P = 0.009), to POST-HA (1.15 +/- 0.21 mg.cm.min; P < 0.001; 98 +/- 35 glands per square centimeter; P < 0.001). No differences in sweat gland output were observed. CONCLUSIONS: A greater omegamax occurred after 8 wk of aerobic training, but omegamax was further augmented with heat acclimation, indicating only a partially increased heat loss capacity with training. These omegamax values may assist future predictions of heat stress risk in untrained/trained unacclimated individuals and trained heat-acclimated individuals. PMID- 28991043 TI - Kinetic Compensations due to Chronic Ankle Instability during Landing and Jumping. AB - INTRODUCTION: Skeletal muscles absorb and transfer kinetic energy during landing and jumping, which are common requirements of various forms of physical activity. Chronic ankle instability (CAI) is associated with impaired neuromuscular control and dynamic stability of the lower extremity. Little is known regarding an intralimb, lower-extremity joint coordination of kinetics during landing and jumping for CAI patients. We investigated the effect of CAI on lower-extremity joint stiffness and kinetic and energetic patterns across the ground contact phase of landing and jumping. METHODS: One hundred CAI patients and 100 matched able-bodied controls performed five trials of a landing and jumping task (a maximal vertical forward jump, landing on a force plate with the test leg only, and immediate lateral jump toward the contralateral side). Functional analyses of variance and independent t-tests were used to evaluate between-group differences for lower-extremity net internal joint moment, power, and stiffness throughout the entire ground contact phase of landing and jumping. RESULTS: Relative to the control group, the CAI group revealed (i) reduced plantarflexion and knee extension and increased hip extension moments; (ii) reduced ankle and knee eccentric and concentric power, and increased hip eccentric and concentric power, and (iii) reduced ankle and knee joint stiffness and increased hip joint stiffness during the task. CONCLUSIONS: CAI patients seemed to use a hip-dominant strategy by increasing the hip extension moment, stiffness, and eccentric and concentric power during landing and jumping. This apparent compensation may be due to decreased capabilities to produce sufficient joint moment, stiffness, and power at the ankle and knee. These differences might have injury risk and performance implications. PMID- 28991044 TI - Mountain Cycling Ultramarathon Effects on Inflammatory and Hemoglobin Responses. AB - PURPOSE: This study aimed to analyze the cumulative physiological burden of repetitive, strenuous exercise held during mountain cycling ultramarathon on regulatory mechanisms of hemoglobin degradation. METHODS: Fifty-five nonprofessional athletes (mean age, 44.8 +/- 7.1 yr) participating in a 9 consecutive-day mountain cycling ultramarathon (TransPortugal) underwent anthropometric, hematological, and biochemical assessments before and immediately after the race. Participants were further stratified as completers (nine courses) or noncompleters and were divided according to the time they took to complete the race. The heme oxygenase-1 (HMOX1) functional genetic polymorphism and haptoglobin (HP) phenotypic variants were also analyzed. RESULTS: Total leukocytes, neutrophil count, and monocyte count increased, whereas decreases in erythrocyte counts and hemoglobin were found between pre- and postultramarathon. Circulating haptoglobin (Hp) was increased, whereas its soluble receptor (sCD163) decreased. Athletes who completed all nine courses presented with increased leukocyte, neutrophil, and erythrocyte counts, as well as hemoglobin, red cell distribution width, total bilirubin, and total cholesterol levels. High sensitivity C-reactive protein and Hp decreased in comparison with noncompleters. HMOX1 and HP genetic polymorphisms were associated with biochemical profile, notably with Hp levels. Analysis of covariance showed a significant effect of HP phenotype in Hp circulating levels at the end of race and on the magnitude of variation from pre- to postrace. CONCLUSIONS: Present findings support a comodulatory influence of genetic- and exercise-associated factors on resulting inflammatory and hemoglobin catabolic marker Hp after highly demanding endurance exercise. PMID- 28991045 TI - Caffeine Ingestion Attenuates Fatigue-induced Loss of Muscle Torque Complexity. AB - : The temporal structure, or complexity, of muscle torque output decreases with neuromuscular fatigue. The role of central fatigue in this process is unclear. PURPOSE: We tested the hypothesis that caffeine administration would attenuate the fatigue-induced loss of torque complexity. METHODS: Eleven healthy participants performed intermittent isometric contractions of the knee extensors to task failure at a target torque of 50% maximal voluntary contraction, with a 60% duty factor (6-s contraction, 4-s rest), 60 min after ingesting 6 mg.kg caffeine or a placebo. Torque and surface EMG signals were sampled continuously. Complexity and fractal scaling of torque were quantified using approximate entropy (ApEn) and the detrended fluctuation analysis (DFA) alpha scaling exponent. Global, central, and peripheral fatigue was quantified using maximal voluntary contractions with femoral nerve stimulation. RESULTS: Caffeine ingestion increased endurance by 30% +/- 16% (mean +/- SD; P = 0.019). Complexity decreased in both trials (decreased ApEn, increased DFA alpha; both P < 0.01), as global, central, and peripheral fatigue developed (all P < 0.01). Complexity decreased significantly more slowly after caffeine ingestion (ApEn, -0.04 +/- 0.02 vs -0.06 +/- 0.01 (P = 0.004); DFA alpha, 0.03 +/- 0.02 vs 0.04 +/- 0.03 (P = 0.024)), as did the rates of global (-18.2 +/- 14.1 vs -23.0 +/- 17.4 N.m.min, P = 0.004) and central (-3.5 +/- 3.4 vs -5.7 +/- 3.9 %.min, P = 0.02) but not peripheral (-6.1 +/- 4.1 vs -7.9 +/- 6.3 N.m.min, P = 0.06) fatigue. CONCLUSIONS: Caffeine ingestion slowed the fatigue-induced loss of torque complexity and increased the time to task failure during intermittent isometric contractions, most likely through central mechanisms. PMID- 28991046 TI - Does a Prolonged Work Day in the Heat Impair Heat Loss on the Next Day in Young Men? AB - PURPOSE: Heat strain is known to be exacerbated on the second of consecutive work days. We therefore evaluated whether prolonged work in the heat would impair whole-body heat loss capacity on the next day. METHODS: To evaluate this possibility, we assessed changes in whole-body heat exchange and heat storage in eight young (26 +/- 4 yr) men during heat stress tests performed on the same day before (day 1) and on the day after (day 2) a prolonged work simulation. Each heat stress test involved three, 30-min bouts of semirecumbent cycling at fixed rates of metabolic heat production (200 W.m (Ex1), 250 W.m (Ex2), and 300 W.m (Ex3)), each separated by 15-min recovery, under hot, dry conditions (40 degrees C, 20% relative humidity). The work simulation (7.5 h) involved three moderate intensity intermittent work bouts (2 h), each separated by 30-min rest breaks, under similarly hot, dry conditions (38 degrees C, 34% relative humidity). Total heat loss (evaporative +/- dry heat exchange) and metabolic heat production were measured using direct and indirect calorimetry, respectively. Body heat storage was quantified as the temporal summation of heat production and loss. RESULTS: Total heat loss did not differ between days 1 and 2 (P = 0.66) and averaged (mean +/- 95% confidence interval) 185 +/- 7 W (Ex1), 233 +/- 7 W (Ex2), and 261 +/- 5 W (Ex3) across test days. Consequently, the change in body heat storage was also similar between days 1 and 2 (P = 0.32), averaging 133 +/- 15 kJ (Ex1), 99 +/- 16 kJ (Ex2), and 184 +/- 15 kJ (Ex3) across test days. CONCLUSIONS: When assessed under controlled laboratory conditions in young men, prolonged work in the heat does not seem to impair whole-body heat loss or exacerbate heat storage on the following day. PMID- 28991047 TI - Vasopressors Do Not Influence Cerebral Critical Closing Pressure During Systemic Inflammation Evoked by Experimental Endotoxemia and Sepsis in Humans. AB - AIM: The aim of this study was to investigate the effects of different vasopressors on the cerebral vasculature during experimental human endotoxemia and sepsis. We used the critical closing pressure (CrCP) as a measure of cerebral vascular tone. METHODS: We performed a prospective pilot study, at the intensive care department (ICU) of a tertiary care university hospital in the Netherlands, in 40 healthy male subjects during experimental human endotoxemia (administration of bacterial lipopolysaccharide [LPS]) and in 10 patients with severe sepsis or septic shock.Subjects in the endotoxemia study were randomized to receive a 5 h infusion of either 0.05 MUg/kg/min noradrenaline (n = 10, "LPS-nor"), 0.5 MUg/kg/min phenylephrine (n = 10, "LPS-phenyl"), 0.04 IU/min vasopressin (n = 10, "LPS-AVP"), or saline (n = 10, "LPS-placebo") starting 1 h before intravenous administration of 2 ng/kg LPS. In patients with sepsis, fluid resuscitation and vasopressor use was at the discretion of the medical team, aiming at normovolemia and a mean arterial pressure (MAP) > 65 mm Hg, using noradrenaline.The mean flow velocity in the middle cerebral artery (MFVMCA) was measured by transcranial Doppler (TCD) with simultaneously recording of heart rate, arterial blood pressure, respiratory rate, and oxygen saturation. CrCP was estimated using the cerebrovascular impedance model. RESULTS: The CrCP decreased in the LPS-placebo group from 52.6 [46.6-55.5] mm Hg at baseline to 44.1 [41.2-51.3] mm Hg at 270 min post-LPS (P = 0.03). Infusion of phenylephrine increased the CrCP in the period before LPS administration from 46.9 [38.8-53.4] to 53.8 [52.9-60.2] mm Hg (P = 0.02), but after LPS administration, a similar decrease was observed compared with the LPS-placebo group. Noradrenaline or vasopressin prior to LPS did not affect the CrCP. The decrease in CrCP after LPS bolus was similar in all treatment groups. The CrCP in the sepsis patients equaled 35.7 [34.4-42.0] mm Hg, and was lower compared with that in the LPS-placebo subjects from baseline until 90 min after LPS (P < 0.01). CONCLUSIONS: Experimental human endotoxemia results in a decreased CrCP due to a loss of vascular resistance of the arterial bed. Vasopressors did not prevent this decrease in CrCP. Findings in patients with sepsis are comparable to those found in subjects after LPS administration.Patients with sepsis, despite treatment with vasopressors, have a risk for low cerebral blood flow and ischemia. PMID- 28991048 TI - Is Inappropriate Response to Cosyntropin Stimulation Test an Indication of Corticosteroid Resistance in Septic Shock? AB - We recently published a comparison of two hydrocortisone dosage regimens in patients with septic shock. We compare the results conferred by the two regimens as a function of the response to cosyntropin stimulation test (CST). Patients with septic shock were treated by one of two hydrocortisone regimens: either a 50 mg intravenous bolus every 6 h during 7 days (200 mg group; n = 49), or a 100-mg initial bolus followed by a continuous infusion of 300 mg daily for 5 days (300 mg group; n = 50). Nonresponders was defined as a CST response of 9 MUg/dL or less. Nonresponders had more severe septic shock, greater fluid resuscitation needs, and greater vasopressor dependence than responders. When analyzed only as a function of CST results, there was no difference in survival between responders and nonresponders. However, analyses crossing CST results and the treatment regimens showed that patients who were responders and in the 300 mg group had significantly less intensive care unit mortality compared with responders in the 200 mg group (respective mortality of 24% vs. 55% [relative risk 0.43, 95% confidence interval, 0.20 to 0.94, P = 0.018]). Multivariate analysis identified baseline blood cortisol as an independent prognostic factor for 28-day mortality in all groups (hazard ratio 1.002, 95% confidence interval, 1.001 to 1.002, P <= 0.0001). The results suggest that in patients who respond to CST, hydrocortisone can provide a dose-dependent benefit. In contrast, nonresponse may indicate corticosteroid resistance. This heterogeneity of response to hydrocortisone may explain the difficulties encountered when trying to demonstrate its benefit in septic shock. PMID- 28991050 TI - Selective LPS Adsorption Using Polymyxin B-Immobilized Fiber Cartridges in Sepsis Patients Following Cardiac Surgery. AB - Sepsis remains the leading cause of morbidity and mortality in intensive care units. The extracorporeal therapy in the complex treatment of sepsis seems to be the most promising direction. The aim of this study was to assess the safety and effectiveness of selective endotoxin adsorption on the basis of the analysis of our own experience with the intensive therapy for sepsis in adult cardiac surgical patients. Our single-center study included 143 patients with sepsis. One hundred and three adult patients received lipopolysaccharide adsorption procedures using Toraymyxin-PMX-20R columns. The historical control group included 30 adult patients received only conservative therapy, and 10 children (6.2-14 kg) received hemoperfusion with Toraymyxin-PMX-0.5R. After the lipopolysaccharide-adsorption course, we noted improving of the hemodynamic and respiratory parameters. A favorable effect of hemoperfusion was a decrease procalcitonin and endotoxin activity assay, expressed by changes of leukocytosis, a normalization of body temperature. The 28-day survival was 53% in the study group and 30% in the control group (P = 0.037). The 28-day survival of children who received selective hemoperfusion was 90%. Our own experience with the use of selective hemoperfusion in a fairly large group of cardiovascular patients with sepsis showed the safety and efficacy of these procedures. PMID- 28991051 TI - Association Between Cardiac Surgery and Mortality Among Patients With Infective Endocarditis Complicated by Sepsis and Septic Shock. AB - BACKGROUND: Sepsis and septic shock are common presentations of infective endocarditis (IE), but little is known about clinical characteristics in this group of patients, use of surgical treatment, and their associations with outcome. We sought to determine the influence of cardiac surgery (CS) on the outcome of patients with IE in different stages of sepsis severity. METHODS: Two hundred ninety four patients with definite IE native or prosthetic valve IE admitted between 2000 and 2011. Prospective evaluation using multivariable logistic regression to evaluate clinical characteristics and outcomes (in hospital and 1-year mortality) in surgically and medically treated patients stratified by severity of sepsis and using new Sepsis-3 definitions. RESULTS: The presence of sepsis or septic shock during IE showed a statistical relationship with increased in-hospital mortality (odds ratio [OR] 8.915, P < 0.001 and OR 35.969, P < 0.001, respectively) after adjusting for other risk factors of poor outcomes (neurological complications, congestive heart failure, and Staphylococcus aureus IE). Surgical treatment had a positive influence on in hospital mortality in patients with sepsis or septic shock and IE (OR 5.157, P < 0.001) as well as on 1-year survival (hazard ratio 3.092, P < 0.001). CONCLUSIONS: The presence of sepsis or septic shock as defined in Sepsis-3 definitions is associated with unfavorable outcomes in patients with IE. Surgical treatment has a positive effect on outcomes (in-hospital mortality and 1-year survival) in patients with IE and sepsis or septic shock. PMID- 28991049 TI - Stearoyl Lysophosphatidylcholine Inhibits Endotoxin-Induced Caspase-11 Activation. AB - Stearoyl lysophosphatidylcholine (LPC) exerts protective effect during endotoxemia and in experimental sepsis, but the underlying mechanism is unclear. Here, we demonstrated that stearoyl LPC could block caspase-11-mediated macrophage pyroptosis. In vitro, stearoyl LPC significantly decreased caspase-11 activation and pyroptosis induced by lipopolysaccharide (LPS) plus cholera toxin subunit B independent of the receptor G2A. Stearoyl LPC did not affect LPS uptake by mouse peritoneal macrophages but did significantly inhibit the interaction between LPS and caspase-11. Moreover, stearoyl LPC treatment conferred significant protection against lethal endotoxemia and significantly reduced the release of IL-1alpha and IL-1beta. These findings identify stearoyl LPC as an inhibitor of LPS-mediated caspase-11 activation. This mechanism could explain the protective action of stearoyl LPC in experimental sepsis and endotoxemia. PMID- 28991052 TI - Somatostatin 2 Receptor Activation in the Rostral Ventrolateral Medulla Does Not Mediate the Decompensatory Phase of Haemorrhage. AB - Decompensation, a critical phase in the response to hemorrhage, is characterized by profound sympathoinhibition and the overriding of baroreflex mediated compensation. As sympathoexcitatory neurons of the rostral ventrolateral medulla (RVLM) maintain vasomotor tone and are essential for sympathetic baroreceptor reflex function, the RVLM is the likely mediator. However, how decompensation occurs is a mystery. Our previous work demonstrated that the inhibitory neuropeptide somatostatin (SST), evokes potent sympathoinhibition. Here we test the hypothesis that, in response to hypovolemia, SST in the RVLM evokes sympathoinhibition, driving decompensation and suppressing baroreflex compensation. We evaluated neuronal activation at sites that contain SST mRNA and project to the RVLM and, in SST2A expressing neurons in the RVLM. We determined the effects on cardiovascular and sympathetic responses to haemorrhage, of bilateral blockade of SST2 receptors in both the RVLM and A1 regions. Haemorrhage in conscious rats evoked c-Fos immunoreactivity in the amygdala, periaqueductal gray, and parabrachial nuclei, regions previously associated with hemorrhage, shown to contain SST and project to the RVLM. Although c-Fos labeling was found throughout the ventrolateral medulla, only a small subset of RVLM SST2A receptor expressing neurons were activated, consistent with the idea that these neurons are inhibited during hemorrhage. However, SST2 receptor antagonists bilaterally injected in the RVLM or the A1 region did not affect the decompensation response to hemorrhage. Thus somatostatin in the RVLM does not mediate decompensation. The physiological role associated with somatostatin-induced sympathoinhibition in the RVLM together with the central mechanisms responsible for decompensation remain elusive. PMID- 28991053 TI - Building Professionalism Through Management Training: New England Public Health Training Center's Low-Cost, High-Impact Model. AB - CONTEXT: Evolving practices, accreditation, and priorities established in Public Health 3.0 are adding to the long-identified need for management training among public health practitioners. PROGRAM: The New England Public Health Training Center is addressing this need with a flexible, open-source, 16-topic training program. The program is designed to build competencies for current and future managers, preparing them for their day-to-day tasks and for the kinds of adaptation suggested by Public Health 3.0 advocates. IMPLEMENTATION: The training program uses live expert instructors for 10 webinars and 2 in-person trainings. Experts have also created the content for multiple self-paced E-Learnings that trainees undertake in addition to the instructor-led sessions. A webinar platform with breakout rooms and an advanced learning management system allows for online discussion and mentor interaction. The course has now been offered, evaluated, and modified 3 times, and the materials are available for noncommercial use by the public health community. EVALUATION: Using the Kirkpatrick training evaluation model, the recent cohort was satisfied (87.5%) with the training, reported identifying actions to apply information learned to their work (85.8%), and experienced statistically significant knowledge gains. Earlier trainees reported work-related behavior change. DISCUSSION: Management training offers the hope of increasing professionalism; creating better, more effective workplaces and programs; and preparing practitioners for an evolving public health landscape. Early results indicate that NEPHTC's program, Managing Effectively in Today's Public Health Environment, is a useful tool in realizing that hope. PMID- 28991054 TI - Raising the Yellow Flag: State Variation in Quarantine Laws. AB - Quarantine is an important but often misused tool of public health. An effective quarantine requires a process that inspires trust in government, only punishes noncompliance, and promotes a culture of social responsibility. Accomplishing successful quarantine requires incentives and enabling factors, payments, job security, and a tiered enforcement plan. In this article, we examine the variation in state-level quarantine laws and assess the effectiveness of these laws and regulations. We find that most states allow for an individual to have a hearing (63%) and to have a voice in burial and cremation procedures (71%), yet are weak on all other individual rights measures. Only 20% of states have provisions to protect employment when an individual is under quarantine, and less than half have plans for safe and humane quarantines. Decision makers at the state and local levels must make a concerted effort to revise and update quarantine laws and regulations. Ideally, these laws and regulations should be harmonized so as to avoid confusion and disruption between states, and public health officials should work with populations to identify and address the factors that will support successful quarantines if they are ever required. PMID- 28991055 TI - Keratoconus Progression in Patients With Allergy and Elevated Surface Matrix Metalloproteinase 9 Point-of-Care Test. AB - PURPOSE: To assess keratoconus (KC) progression in patients with allergies who also tested positive to surface matrix metalloproteinase 9 (MMP-9) point-of-care test. METHODS: Prospective comparative study including 100 stage I-II keratoconic patients, mean age 16.7+/-4.6 years. All patients underwent an anamnestic questionnaire for concomitant allergic diseases and were screened with the MMP-9 point-of-care test. Patients were divided into two groups: patients KC with allergies (KC AL) and patients KC without allergies (KC NAL). Severity of allergy was established by papillary subtarsal response grade and KC progression assessed by Scheimpflug corneal tomography, corrected distance visual acuity (CDVA) measurement in a 12-month follow-up. RESULTS: The KC AL group included 52 patients and the KC NAL group 48. In the KC AL group, 42/52 of patients (81%) were positive to MMP-9 point-of-care test versus two positive patients in the KC NAL group (4%). The KC AL group data showed a statistically significant decrease of average CDVA, from 0.155+/-0.11 to 0.301+/-0.2 logarithm of the minimum angle of resolution (P<0.005) at 12 months; Kmax value increased significantly, from 50.2 D+/-2.7 to 55.2 D+/-1.9 on average. The KC NAL group revealed a slight KC progression without statistically significant changes. Pearson correlation test showed a high correlation between Kmax worsening and severity of PSR in the KC AL group. CONCLUSIONS: The study demonstrated a statistically significant progression of KC in patients with concomitant allergies, positive to MMP-9 point of-care test versus negative. A high correlation between severity of allergy and KC progression was documented. PMID- 28991056 TI - Ultrafast Track Robotic-Assisted Minimally Invasive Coronary Artery Surgical Revascularization. AB - OBJECTIVE: Contemporary anesthetic techniques have enabled shorter sedation and early extubation in off-pump and minimally invasive coronary artery bypass (CABG) surgery. Robotic-assisted CABG represents the optimal surgical approach for ultrafast track anesthesia, with patients able to bypass the cardiac surgical intensive care unit with recovery in the postanesthesia care unit (PACU) and inpatient ward. METHODS: In-hospital postoperative outcomes from ninety patients who underwent either elective or urgent robotically-assisted CABG at our institution were reviewed. These patients were carefully selected by a multidisciplinary team to undergo fast-track anesthesia: extubation in the operating room, 4-hour recovery in the postanesthesia care unit and transfer to the inpatient ward. Intrathecal, paravertebral local, and patient-controlled anesthesia techniques were used to facilitate transition to oral analgesics. RESULTS: Average patient age was 61 +/- 9 years. Sixty-six patients (73%) were male. Seventy cases were elective, and 20 patients required urgent revascularization. All patients underwent intraoperative angiography after graft construction, which revealed Fitzgibbon class A grafts. There were no in-hospital mortalities. One patient required re-exploration for bleeding, through the same minimally invasive incision, did not require conversion to sternotomy for bleeding, and was transferred to the intensive care unit postexploration for bleeding for standard postoperative care. Postoperative complications were limited to one superficial wound infection. The mean hospital length of stay was 3.5 +/- 1.17 days. CONCLUSIONS: In patients undergoing robotic-assisted CABG, ultrafast-track cardiac surgery with immediate postprocedure extubation and transfer to the inpatient ward has been demonstrated to be safe with no increase in perioperative morbidity or mortality. It requires a dedicated heart team with a carefully selected group of patients. Avoiding cardiac surgical intensive care unit expedites recovery, with possible avoidance of infection and early discharge from hospital. PMID- 28991057 TI - Minimally Invasive Mitral Valve Annuloplasty With Realignment of Both Papillary Muscles for Correction of Type IIIb Functional Mitral Regurgitation. AB - OBJECTIVE: Pathophysiological background of type IIIb functional mitral regurgitation (FMR) is a progressively increasing distance between papillary muscle tips and mitral annular plane. Standard surgical treatment of such FMR by means of undersized mitral annuloplasty is associated with a high recurrence rate. METHODS: We propose a modified subannular maneuver to correct type IIIb FMR while combining undersized annuloplasty with a controlled realignment of both papillary muscles, thereby fixing the distance between mitral annular plane and papillary muscle tips. The differences of this subannular maneuver as compared with the previously published techniques are the following: (1) controlled realignment of both papillary muscles, (2) fixation of the papillary muscles to mitral annulus distance on an annuloplasty ring, and (3) application in a three dimensional endoscopic minithoracotomy setting. RESULTS: We describe a surgical technique of minimally invasive mitral valve repair performed due to severe type IIIb FMR, which includes a modified subannular maneuver to realign both papillary muscles. Preliminary results of the first 10 patients who underwent this procedure at our institution are presented. There was no in-hospital mortality and follow-up echocardiography (mean +/- SD echocardiographic follow-up = 10 +/- 6 months) demonstrated stable functional results. CONCLUSIONS: Our initial experience indicates that adding of this subannular maneuver to the standard annuloplasty and thereby fixing the distance between papillary muscles and mitral annular plane have a potential to improve results of surgical FMR treatment. PMID- 28991058 TI - Red Cell Distribution Width After Subarachnoid Hemorrhage. AB - BACKGROUND: High red cell distribution width (RDW) values have been associated with increased hospital mortality in critically ill patients, but few data are available for subarachnoid hemorrhage (SAH). METHODS: We analyzed an institutional database of adult (>18 y) patients admitted to the Department of Intensive Care after nontraumatic SAH between January 2011 and May 2016. RDW (normal value, 10.9% to 13.4%) was obtained daily from admission for a maximum of 7 days, from routine blood analysis. We recorded the occurrence of delayed cerebral ischemia (DCI), and neurological outcome (assessed using the Glasgow Outcome Scale [GOS]) at 3 months. RESULTS: A total of 270 patients were included (median age 54 y-121/270 male [45%]), of whom 96 (36%) developed DCI and 109 (40%) had an unfavorable neurological outcome (GOS, 1 to 3). The median RDW on admission was 13.8 [13.3 to 14.5]% and the highest value during the intensive care unit (ICU) stay 14.2 [13.6 to 14.8]%. The RDW was high (>13.4%) in 177 patients (66%) on admission and in 217 (80%) at any time during the ICU stay. Patients with a high RDW on admission were more likely to have an unfavorable neurological outcome. In multivariable regression analysis, older age, a high WFNS grade on admission, presence of DCI or intracranial hypertension, previous neurological disease, vasopressor therapy and a high RDW (OR, 1.1618 [95% CI, 1.213-2.158]; P=0.001) during the ICU stay were independent predictors of unfavorable neurological outcome. CONCLUSIONS: High RDW values were more likely to result in an unfavorable outcome after SAH. This information could help in the stratification of SAH patients already on ICU admission. PMID- 28991059 TI - Analgesia Nociception Index Monitoring During Supratentorial Craniotomy. AB - BACKGROUND: Objective monitoring of pain during and after surgery has been elusive. Recently, Analgesia Nociception Index (ANI) monitor based on the high frequency component of heart rate variability has been launched into clinical practice. We monitored analgesia during craniotomy using ANI monitor and compared it with cardiovascular parameters and response entropy (RE) of entropy monitor. MATERIALS AND METHODS: In 21 patients undergoing a craniotomy for a supratentorial lesion, we monitored ANI, heart rate (HR), mean arterial pressure (MAP), state entropy, and RE throughout the surgery. Also, ANI, hemodynamic variables and spectral entropy values were noted at the times of maximal stimulation, such as induction, intubation, head pin fixation, skin incision, craniotomy, durotomy, and skin closure. We also compared ANI with RE during administration of bolus doses of fentanyl. RESULTS: There was an inverse correlation between ANI values and the hemodynamic changes. When the HR and MAP increased, ANI decreased suggesting a good correlation between hemodynamics and ANI values during the times of maximal stimulation. State entropy and RE did not change significantly in response to bolus doses of fentanyl administered during the course of surgery, while ANI increased significantly. CONCLUSION: In neurosurgical patients undergoing elective supratentorial craniotomy, ANI measures response to noxious stimuli with at least as much reliability as hemodynamic variables and changes in ANI parallel the changes in HR and MAP. ANI is superior to RE for measurement of response to noxious stimuli. PMID- 28991060 TI - Hemodynamic Instability and Cardiovascular Events After Traumatic Brain Injury Predict Outcome After Artifact Removal With Deep Belief Network Analysis. AB - BACKGROUND: Hemodynamic instability and cardiovascular events heavily affect the prognosis of traumatic brain injury. Physiological signals are monitored to detect these events. However, the signals are often riddled with faulty readings, which jeopardize the reliability of the clinical parameters obtained from the signals. A machine-learning model for the elimination of artifactual events shows promising results for improving signal quality. However, the actual impact of the improvements on the performance of the clinical parameters after the elimination of the artifacts is not well studied. MATERIALS AND METHODS: The arterial blood pressure of 99 subjects with traumatic brain injury was continuously measured for 5 consecutive days, beginning on the day of admission. The machine-learning deep belief network was constructed to automatically identify and remove false incidences of hypotension, hypertension, bradycardia, tachycardia, and alterations in cerebral perfusion pressure (CPP). RESULTS: The prevalences of hypotension and tachycardia were significantly reduced by 47.5% and 13.1%, respectively, after suppressing false incidents (P=0.01). Hypotension was particularly effective at predicting outcome favorability and mortality after artifact elimination (P=0.015 and 0.027, respectively). In addition, increased CPP was also statistically significant in predicting outcomes (P=0.02). CONCLUSIONS: The prevalence of false incidents due to signal artifacts can be significantly reduced using machine-learning. Some clinical events, such as hypotension and alterations in CPP, gain particularly high predictive capacity for patient outcomes after artifacts are eliminated from physiological signals. PMID- 28991062 TI - Electron Microscopy of Dural and Arachnoid Disruptions After Subarachnoid Block. AB - BACKGROUND: It has been customary to attribute postdural puncture headache (PDPH) incidence and severity to size and nature of the dural hole produced during major neuraxial blockade or diagnostic dural puncture. Needle orientation in relation to the direction of dural fibers was thought to be of importance because of the propensity for horizontal bevel placement to cause cutting rather than splitting of the dural fibers. METHODS: In vitro punctures of stringently quality controlled human dural sac specimens were obtained with 27-gauge (27G) Whitacre needle (n = 33), with 29G Quincke used parallel to the spinal axis (n = 30), and with 29G Quincke in perpendicular approach (n = 40). The samples were studied with a scanning electron microscope, and the perimeter, appearance, and area (%) of the lesion were calculated. RESULTS: When using small 27G to 29G needles, neither needle tip characteristics nor needle orientation had a substantial bearing on the damage to dural fibers in the dural lesion. Of ultimate importance was the characteristic and size of the hole in the arachnoid. Arachnoid layer lesions produced by different types of spinal needles were not markedly different. CONCLUSIONS: Accepted theories of the etiology of PDPH need to be revised. This article marks the first time that arachnoid layer damage has been quantified. Dural fibers tend to have sufficient "memory" to close back the hole created by a spinal needle, whereas arachnoid has diminished capacity to do so. The pathogenesis of PDPH and its resolution algorithm are a far more complex process that involves many more "stages" of development than hitherto imagined. PMID- 28991061 TI - Determination of ED50 and ED95 of 0.5% Ropivacaine in Adductor Canal Block to Produce Quadriceps Weakness: A Dose-Finding Study. AB - BACKGROUND AND OBJECTIVES: Adductor canal block (ACB) is popular for knee analgesia because of its favorable effect on quadriceps strength. The aim of this study was to find the minimum volume of local anesthetic, which can be injected into the ACB that would result in quadriceps weakness. METHODS: This nonrandomized study used an up-and-down sequential allocation design. Twenty-six patients scheduled to undergo arthroscopic knee surgery received an ultrasound guided ACB preoperatively. The initial volume of ropivacaine 0.5% injected was 30 mL, which was subsequently increased or decreased by 2 mL, depending on whether the previous subject had a 30% reduction in quadriceps function. The minimum effective volume in 50% of patients was determined using Dixon-Massey up-and-down method. The effective volume in 95% of patients was then calculated using probit transformation. RESULTS: The ED50 (minimum effective anesthetic volume in 50% of the subjects) needed for a 30% decrease in quadriceps power was 46.5 mL (95% confidence interval, 45.01-50.43 mL), and estimated ED95 (minimum effective anesthetic volume in 95% of the subjects) was 50.32 mL (95% confidence interval, 48.66-67.26 mL). The local anesthetic volume injected correlated with degree of quadriceps weakness at 20 minutes postblock (P < 0.001) and in the postanesthesia recovery unit (P = 0.032). CONCLUSIONS: Significant quadriceps weakness is unlikely when clinically representative volumes of 0.5% ropivacaine is used for ACB performed using sonographic landmarks. CLINICAL TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov, identifier NCT02541552. PMID- 28991064 TI - Improving Nurse Competencies for Using Evidence in Practice: A Pilot Study of the Language of Data Program. AB - Nursing professional development practitioners are in a key position to use tools that foster nurses' interpretation of research findings for increased use of evidence in practice. An online course was developed to teach statistics as language. The feasibility and efficacy of this "Language of Data" program were examined in a pilot study with a convenience sample from inpatient settings. Recognition and interpretation of statistical symbols significantly improved after the intervention. Knowledge, confidence, and accuracy also improved. The Language of Data program may be used by nursing professional development practitioners to improve nurses' adoption of evidence-based practice by furthering their ability to translate science. PMID- 28991063 TI - Dose-Response Curves for Intrathecal Bupivacaine, Levobupivacaine, and Ropivacaine Given for Labor Analgesia in Nulliparous Women. AB - BACKGROUND AND OBJECTIVES: Bupivacaine, levobupivacaine, and ropivacaine are often given intrathecally for labor analgesia, but limited data are available for their dose-response properties in this context. The objective of this study was to describe the dose-response curves of these local anesthetics when given intrathecally for labor analgesia, to determine values for D50 (dose producing a 50% response) and to compare the calculated values of D50 for levobupivacaine and ropivacaine with those for bupivacaine. METHODS: With ethics approval and written consent, we randomized 270 nulliparous laboring patients requesting neuraxial analgesia at 5-cm cervical dilation or less to receive a single dose of intrathecal local anesthetic without opioid as part of a combined spinal-epidural technique. Patients received either bupivacaine, levobupivacaine, or ropivacaine at a dose of 0.625, 1.0, 1.5, 2.5, 4.0, or 6.25 mg (n = 15 per group). Visual analog scale pain scores were measured for 15 minutes, after which further analgesia and management were at the clinician's discretion. The primary end point was percentage reduction of pain score at 15 minutes. Logistic sigmoidal dose-response curves were fitted to the data using nonlinear regression, and D50 values were calculated for each drug. RESULTS: Data were analyzed from 270 patients. Patient characteristics were similar between groups. The calculated D50 and 95% confidence interval values were as follows: bupivacaine, 1.56 mg (1.25 1.94 mg); ropivacaine, 1.95 mg (1.57-2.43 mg); and levobupivacaine, 2.20 mg (1.76 2.73 mg). CONCLUSIONS: The results of this study support previous work showing that intrathecal levobupivacaine and ropivacaine are less potent than bupivacaine. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (identifier: ChiCTR-TRC-09000773) and Centre of Clinical Trials Clinical Registry of the Chinese University of Hong Kong (identifier: CUHK_CCT00245). PMID- 28991065 TI - Clinically Acceptable Optimized Dose Reduction in Computed Tomographic Imaging of Necrotizing Pancreatitis Using a Noise Addition Software Tool. AB - OBJECTIVE: This study aimed to determine potential radiation dose reduction of contrast-enhanced computed tomography (CECT) for imaging necrotizing pancreatitis (NP) using a noise addition tool. METHODS: Eighty-four patients were identified with at least 1 abdominopelvic CECT for NP within a 2-year period. Sixty consecutive scans were selected as reference radiation dose data sets. A noise addition software was used to simulate 4 data sets of increased noise. Readers rated confidence for identifying (i) anatomic structures, (ii) complications of NP, and (iii) diagnostic acceptability. Noise and dose levels were identified at acceptability threshold where observer scores were statistically indistinguishable from full-dose computed tomographies. RESULTS: Observers' perception of image tasks decreased progressively with increasing noise (P < 0.05). Acceptability and statistical analysis indicated that noise can be increased from 10 to 25 HU corresponding to an 84% reduction in dose without change in observer perception (P < 0.05). CONCLUSIONS: Higher image noise levels may be tolerated in CECT in patients with NP. PMID- 28991066 TI - Defense Automated Neurobehavioral Assessment Accurately Measures Cognition in Patients Undergoing Electroconvulsive Therapy for Major Depressive Disorder. AB - OBJECTIVES: The Defense Automated Neurobehavioral Assessment (DANA) is an electronic cognitive test battery. The present study compares DANA to the standard Mini-Mental State Examination (MMSE) in subjects undergoing electroconvulsive therapy for the treatment of major depressive disorder. METHODS: Seventeen inpatient subjects in the Johns Hopkins Hospital Department of Psychiatry were administered longitudinal paired DANA and MMSE tests (7.6 +/- 4.1 per patient) from January 10, 2014 to September 26, 2014. Regression analyses were conducted (with or without MMSE scores of 30) to study the impact of the MMSE upper limit, and within-subject regression analyses were conducted to compare MMSE and DANA scores over time. RESULTS: Statistically significant relationships were measured between DANA and MMSE scores. Relationships strengthened when MMSE scores of 30 were omitted from analyses, demonstrating a ceiling effect of the MMSE. Within-subject analyses revealed relationships between MMSE and DANA scores over the duration of the inpatient stay. CONCLUSIONS: Defense Automated Neurobehavioral Assessment is an electronic, mobile, repeatable, sensitive, and valid method of measuring cognition over time in depressed patients undergoing electroconvulsive therapy treatment. Automation of the DANA allows for more frequent cognitive testing in a busy clinical setting and enhances cognitive assessment sensitivity with a timed component to each test. PMID- 28991067 TI - A 6-Month Follow-up Case Study of Low-Frequency Right Prefrontal Repetitive Transcranial Magnetic Stimulation in Treatment-Resistant Bipolar Depression. PMID- 28991068 TI - Regulation of Electroconvulsive Therapy: A Systematic Review of US State Laws. AB - OBJECTIVES: The goal of this study was to systematically review current US state laws on electroconvulsive therapy (ECT) in order to provide a comprehensive resource to educate practitioners, potential patients, and lawmakers. METHODS: Individual state legislative Web sites were searched by 2 independent authors using the following search terms: "electroconvulsive therapy," "convulsive therapy," "electroconvulsant therapy," "electroshock therapy," and "shock therapy" from March 2017 to May 2017. All sections of state law pertaining to ECT were reviewed, and pertinent data regarding consent, age restrictions, treatment limitations, required reporting, defined qualified professionals, fees, and other information were extracted. RESULTS: State regulation on ECT widely varied from none to stringent requirements. There were 6 states without any laws pertaining to ECT. California, Illinois, Massachusetts, Missouri, New York, South Dakota, Tennessee, and Texas were noted to be the most regulatory on ECT. CONCLUSIONS: There are no US national laws on ECT leaving individual state governments to regulate treatment. Whereas some states have detailed restrictions on use, other states have no regulation at all. This variation applies to multiple areas of ECT practice, including who can receive ECT, who can provide informed consent, who can prescribe or perform ECT, and what administrative requirements (eg, fees, reporting) must be met by ECT practitioners. Knowledge of these state laws will help providers not only to be aware of their own state's regulations, but also to have a general awareness of what other states mandate for better patient care and utilization of ECT. PMID- 28991069 TI - Advocacy: The value of staying calm in the eye of the storm. PMID- 28991070 TI - Looking into secondary lymphedema. PMID- 28991071 TI - New Drugs 2017, part 3. PMID- 28991072 TI - Surveillance of Duodenal Polyposis in Familial Adenomatous Polyposis: Should the Spigelman Score Be Modified? PMID- 28991073 TI - Spigelman Scoring System Underestimates the Risk of Ampullary and Duodenal Carcinoma in Patients With Familial Adenomatous Polyposis With Duodenal Polyposis. PMID- 28991074 TI - Clinical Practice Guidelines for the Treatment of Rectal Prolapse. PMID- 28991075 TI - Rectal Prolapse. PMID- 28991076 TI - Expert Commentary on Rectal Prolapse. PMID- 28991077 TI - Surveillance of Duodenal Polyposis in Familial Adenomatous Polyposis: Should the Spigelman Score Be Modified? AB - BACKGROUND: Duodenal polyposis is a manifestation of adenomatous polyposis that predisposes to duodenal or ampullary adenocarcinoma. Duodenal polyposis is monitored by upper GI endoscopies and may require iterative resections and prophylactic radical surgical treatment when malignancy is threatening. OBJECTIVE: The purpose of this study was to evaluate severity scoring for surveillance and treatment in a large series of duodenal polyposis. DESIGN: From 1982 to 2014, every patient surveyed by upper GI endoscopies for duodenal polyposis was included. SETTINGS: The study was conducted at a single tertiary care center. PATIENTS: We performed 1912 upper GI endoscopies in 437 patients (median = 3; interquartile range, 2-6 endoscopies). MAIN OUTCOME MEASURES: Conservative treatment was performed in 103 patients (159 endoscopic and 17 surgical resections), whereas radical surgical treatment (Whipple procedure or duodenectomy) was required in 52 (median age, 47.5 y; range, 43.0-57.3 y) because of high-grade dysplasia or unresectable lesions. RESULTS: Genes involved were APC (n = 274; 62.7%) and MUTYH (n = 21; 4.8%). First upper GI endoscopies (median age, 32 y; range, 21-44 y) revealed duodenal polyposis in 190 (43.5%). Rates of low-grade dysplasia, high-grade dysplasia, and duodenal or ampulary adenocarcinoma at 5 years were 65% (range, 61.7%-66.9%), 12.1% (range, 10.3% 13.9%), and 2.4% (range, 1.5%-3.3%), whereas 10-year rates were 75.8% (range, 73.1%-78.5%), 20.8% (range, 18.2%-23.4%), and 5.4% (range, 3.8%-7.0%). The rate of ampullary abnormalities rose during surveillance from 18.3% at the first upper GI endoscopies to 47.4% at the fourth. Predictive factors for high-grade dysplasia were age at first upper GI endoscopy, type and age of colorectal surgery, Spigelman score, presence of an ampullary abnormality, and number of endoscopic treatments. In multivariate analysis, only age at first upper GI endoscopy and presence of an ampullary abnormality were independent predictive factors. Histologic analysis after radical surgical treatment showed high-grade dysplasia in 30 patients and duodenal or ampulary adenocarcinoma in 11 (4 patients had lymph node involvement). LIMITATIONS: The study was limited by its retrospective analysis of a prospective database. CONCLUSIONS: More than 20% of patients developed high-grade dysplasia with duodenal polyposis after 10 years. Iterative endoscopic resections allowed extended control, but surgery remained necessary in 12% of the patients and happened too late in many cases; 20% of those operated had developed duodenal or ampulary adenocarcinoma, whereas 8% exhibited malignancy with lymph node involvement. The trigger for prophylactic surgery required a more accurate predictive score leading to closer endoscopic surveillance. Modifying the Spigelman score by accounting for ampullary abnormalities should be considered as a means to increase compliance with closer endoscopic follow-up in high-risk patients. See Video Abstract at http://links.lww.com/DCR/A430. PMID- 28991078 TI - Long-term Deleterious Impact of Surgeon Care Fragmentation After Colorectal Surgery on Survival: Continuity of Care Continues to Count. AB - BACKGROUND: Surgical care fragmentation at readmission impacts short-term outcomes. However, the long-term impact of surgical care fragmentation is unknown. OBJECTIVE: The purpose was to evaluate the impact of surgical care fragmentation, encompassing both surgeon and hospital care, at readmission after colorectal surgery on 1-year survival. DESIGN: This was a retrospective cohort study. SETTING: The study included patients undergoing colorectal resection in New York State from 2004 to 2014. PATIENTS: Included were 20,016 patients undergoing colorectal resection who were readmitted within 30 days of discharge and categorized by source-of-care fragmentation. Each readmission was classified by the source of fragmentation: readmission to the index hospital and managed by another provider, readmission to another hospital by the index surgeon, and readmission to another hospital by another provider. Patients readmitted to the index hospital and managed by the index surgeon served as controls. MAIN OUTCOME MEASURES: One-year overall survival and 1-year colorectal cancer-specific survival were the outcomes measured. RESULTS: After propensity adjustment, surgeon care fragmentation was independently associated with decreased survival. In comparison with patients without surgical care fragmentation (patients readmitted to the index hospital and managed by the index surgeon), patients readmitted to the index hospital and managed by another provider had over a 2 fold risk (HR, 2.33; 95% CI, 2.10-2.60) and patients readmitted to another hospital by another provider had almost a 2-fold risk (HR, 1.91; 95% CI, 1.63 2.25) of 1-year mortality. Among 9545 patients with a colorectal cancer diagnosis, surgical care fragmentation was once again associated with decreased survival with patients readmitted to the index hospital and managed by another provider having a HR of 2.12 (95% CI, 1.76-2.56) and patients readmitted to another hospital by another provider having a HR of 1.57 (95% CI, 1.17-2.11) compared with patients readmitted to the index hospital and managed by the index surgeon. LIMITATIONS: Limitations include possible miscoding of data, retrospective design, and selection bias. CONCLUSIONS: After accounting for patient, index hospital, index surgeon, and readmission factors, there is a significant 2-fold decrease in survival associated with surgeon care fragmentation regardless of hospital continuity. See Video Abstract at http://links.lww.com/DCR/A431. PMID- 28991079 TI - Peritoneal Involvement Is More Common Than Nodal Involvement in Patients With High-Grade Appendix Tumors Who Are Undergoing Prophylactic Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy. AB - BACKGROUND: Right hemicolectomy is routinely recommended in patients with histologic findings of high-grade appendix tumors after appendicectomy. Undetected peritoneal disease may be encountered at surgery. In high-grade appendix tumors with disease detected radiologically, complete cytoreduction may not be possible and outcomes poor. For these reasons, we adopted a policy of prophylactic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. OBJECTIVE: The purpose of this study was to quantify the rates of peritoneal and nodal metastatic disease in patients with high-grade appendix tumors without obvious metastatic disease and to report the long-term outcomes of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in these patients. DESIGN: Data regarding peritoneal and nodal metastatic disease were extracted from surgical and histologic records. SETTINGS: The study was conducted at a high volume tertiary referral center for peritoneal malignancy. PATIENTS: Patients referred with histologically high-grade appendix tumors at appendicectomy, without detectable metastatic spread, between January 1994 and September 2016 were included MAIN OUTCOME MEASURES:: A total of 62 patients with high-grade pathology at appendicectomy, without clinical or radiological peritoneal disease, underwent complete cytoreduction with hyperthermic intraperitoneal chemotherapy. RESULTS: Thirty-five (57%) of 62 patients had peritoneal disease (median peritoneal cancer index 5 (range, 1-28)). Eleven (31%) of 35 had microscopic peritoneal disease. Overall, 23 (37%) of 62 had peritoneal disease beyond the confines of a standard right hemicolectomy. Nine (15%) of 62 had nodal involvement. Mean overall and disease-free survival were 110.9 (95% CI, 94.8 127.0 mo) and 102.1 months (95% CI, 84.3-119.9 mo), with 5-year overall and disease-free survival of 83.2% and 76.0%. LIMITATIONS: The retrospective nature limits the interpretation of these results. CONCLUSIONS: Complete cytoreduction was achieved in all of the patients, with excellent long-term survival. The incidence of peritoneal spread (57%) compared with nodal involvement (15%) supports cytoreductive surgery and hyperthermic intraperitoneal chemotherapy as definitive treatment rather than prophylaxis in patients with high-grade appendix tumors, even without radiologically detectable disease. High-grade appendix tumors benefit from early aggressive operative management to deal with potential peritoneal and nodal spread and should be considered for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. See Video Abstract at http://links.lww.com/DCR/A360. PMID- 28991080 TI - Prospective Trial Evaluating the Surgical Anastomosis at One-Year Colorectal Cancer Surveillance: CT Colonography Versus Optical Colonoscopy and Implications for Patient Care. AB - OBJECTIVE: The aim of this study was to compare the accuracy of CT colonography versus optical colonoscopy for neoplastic involvement at the surgical anastomosis 1 year after curative-intent colorectal cancer resection. DESIGN, SETTING, PATIENTS, AND INTERVENTIONS: Two hundred one patients (mean age, 58.6 years; 117 men, 84 women) underwent same-day contrast-enhanced CT colonography and colonoscopy approximately 1 year (mean, 12.1 months; median, 11.9 months) after colorectal cancer resection as part of a prospective, multicenter trial. All patients enrolled were without clinical evidence of disease and considered low risk for recurrence (stage I-III). MAIN OUTCOME MEASURES: Suspected neoplastic lesions within 5 cm of the colonic anastomosis were recorded at CT colonography, with subsequent colonoscopy performed for the same, with segmental unblinding of colonography findings. Anastomotic region biopsy or polypectomy was performed at the endoscopist's discretion. RESULTS: None of the 201 patients had intraluminal anastomotic cancer recurrence or advanced neoplasia (or metachronous cancers). CT colonography detected extramural perianastomotic recurrence in 2 patients (1.0%); neither was detected at colonoscopy. Only 2 patients (1.0%; 2/201) were called positive at CT colonography for intraluminal anastomotic nondiminutive lesions (7 to 8-mm polyps), which were confirmed at colonoscopy but nonneoplastic at histopathology. At optical colonoscopy, the anastomosis was deemed abnormal and/or biopsied in 10.0% (20/201), yielding only 1 nondiminutive benign neoplasm (7-mm tubular adenoma). LIMITATIONS: The lack of luminal cancer recurrence in our lower-risk cohort precludes assessment of sensitivity for detection, rendering the study underpowered in this regard. Potential cost savings of combined CT/CT colonography over the standard CT/colonoscopy approach were not assessed. CONCLUSIONS: Relevant intraluminal anastomotic pathology appears to be very uncommon 1 year after colorectal cancer resection in lower-risk cohorts. Unlike colonoscopy, diagnostic contrast-enhanced CT colonography effectively evaluates both the intra- and extraluminal aspects of the anastomosis. See Video Abstract at http://links.lww.com/DCR/A471. PMID- 28991081 TI - A New Prediction Model for Local Recurrence After Curative Rectal Cancer Surgery: Development and Validation as an Asian Collaborative Study. AB - BACKGROUND: Local recurrence is one of the remaining problems in rectal and rectosigmoid cancer, and it is sometimes difficult to treat. OBJECTIVE: This study aimed to explore various factors that are highly related to local recurrence and to develop a new prediction model for local recurrence after curative resection. DESIGN: This is a retrospective cohort study SETTINGS:: This study was conducted at 2 academic hospitals in Japan and Korea. PATIENTS: A total of 2237 patients with stage I to III rectal and rectosigmoid cancer who underwent a curative operation with a negative circumferential margin were selected. INTERVENTIONS: Surgical treatment was the intervention. MAIN OUTCOME MEASURES: Local recurrence was the primary outcome measure. RESULTS: A total of 1232 patients were selected, and rectosigmoid cancer with rare local recurrence (2/221) was excluded. A different set of 792 patients with rectal cancer were chosen for validation. Multivariate analysis showed the following factors as significant for local recurrence: poorly differentiated tumor (HR, 11.2; 95% CI, 4.5-28.0), tumor depth (HR, 5.0), lymph node metastasis (HR, 4.1), operative procedure (HR, 3.2), postoperative complications (HR, 2.9), tumor location (HR, 2.6), and CEA level (HR, 2.4); a new prediction score was created by using these factors. A poorly differentiated tumor was assigned 2 points, and all other factors were assigned 1 point each. Patients who scored more than 5 points (n = 21) were judged as "high risk," with a 2-year local recurrence rate of 66.5%. The new predictive model could also separate the patients into different risk groups in the validation set. The high-risk group had higher recurrence rates than medium- and low-risk groups (2-year local recurrence rate: 41%, 15%, and 2.1%). LIMITATIONS: This study was limited by its retrospective nature and potential for selection bias. CONCLUSIONS: Seven factors were shown to be significantly correlated with the local recurrence of rectal cancer, and the usefulness of this new prediction model was demonstrated. See Video Abstract at http://links.lww.com/DCR/A429. PMID- 28991082 TI - A Distal Resection Margin of <=1 mm and Rectal Cancer Recurrence After Sphincter Preserving Surgery: The Role of a Positive Distal Margin in Rectal Cancer Surgery. AB - BACKGROUND: There is little information about the prognostic value of a microscopically positive distal margin in patients who have rectal cancer. OBJECTIVE: We aimed to investigate the influence of a distal margin of <=1 mm on oncologic outcomes after sphincter-preserving resection for rectal cancer. DESIGN: This is a retrospective cohort study. SETTINGS: The study was conducted at 2 hospitals. PATIENTS: A total of 6574 patients underwent anterior resection for rectal cancer from January 1999 to December 2014; 97 (1.5%) patients with a distal margin of <=1 mm were included in this study. For comparative analyses, patients were matched with 194 patients with a negative distal margin (>1 mm) according to sex, age, BMI, ASA score, neoadjuvant treatment, tumor location, and stage. MAIN OUTCOME MEASURES: The oncologic outcomes of the 2 groups were compared. RESULTS: Perineural and lymphovascular invasion rates were significantly higher in patients with a positive distal margin (54.6% vs 28.9%; 67.0% vs 42.8%; both p < 0.001) compared with to patients with negative distal margin. Comparison between microscopically positive and negative distal margin showed worse oncologic outcomes in patients with a microscopically positive distal margin, including 5-year local recurrence rate (24.1% vs 12.0%, p = 0.005); 5-year distant recurrence rate (35.5% vs 20.2%, p = 0.011); 5-year disease-free survival (45.5% vs 69.5%, p < 0.001); and 5-year OS (69.2% vs 79.7%, p = 0.004). Among the 97 patients with a microscopically positive distal margin, the 5-year disease-free survival rate was higher in patients who received adjuvant therapy (52.0% vs 30.7%, p = 0.089). LIMITATIONS: This is a retrospective study; bias may exist. CONCLUSIONS: A distal margin of 1 mm is associated with worse oncologic results. Our data indicate the importance of achieving a clear distal margin in the surgical treatment of rectal cancer. Adjuvant therapy should be used in these patients to reduce recurrence. See Video Abstract at http://links.lww.com/DCR/A408. PMID- 28991083 TI - Prediction of N0 Irradiated Rectal Cancer Comparing MRI Before and After Preoperative Chemoradiotherapy. AB - BACKGROUND: The prediction of lymph node status using MRI has an impact on the management of rectal cancer, both before and after preoperative chemoradiotherapy. OBJECTIVE: The purpose of this study was to maximize the negative predictive value and sensitivity of mesorectal lymph node imaging after chemoradiotherapy because postchemoradiation node-negative patients may be treated with rectum-sparing approaches. DESIGN: This was a retrospective study. SETTINGS: The study was conducted at a tertiary care hospital. PATIENTS: Sixty four patients with locally advanced rectal cancer who underwent preoperative chemoradiotherapy and MRI for staging and the assessment of response were evaluated. MAIN OUTCOME MEASURES: The sums of the sizes of all mesorectal lymph nodes in each patient on both prechemoradiotherapy and postchemoradiotherapy imaging data sets were calculated to determine the lymph node global size reduction rates, taking these to be the outcomes of the histopathologic findings. Other included measures were interobserver agreement regarding the prediction of node status based on morphologic criteria and the diagnostic performance of contrast-enhanced images. RESULTS: Using a cutoff value of a 70% lymph node global size reduction rate with only 15 node-positive patients on histopathology, the sensitivity in the prediction of nodal status and negative predictive value were 93% (95% CI, 70.2%-98.8%) and 97% (95% CI, 82.9%-99.8%) for observer 1 and 100% (95% CI, 79.6%-100%) and 100% (95% CI, 62.9%-100%) for observer 2. The areas under the receiver operating characteristic curves for the 2 observers were 0.90 (95% CI, 0.82-0.98; p < 0.0001) for observer 1 and 0.65 (95% CI, 0.50-0.79; p = 0.08) for observer 2. The efficacy of the morphologic criteria and contrast enhanced images in predicting node status was limited after chemoradiotherapy. LIMITATIONS: This study is limited by its small sample size and retrospective nature. CONCLUSIONS: Assessing the lymph node global size reduction rate value reduces the risk of undetected nodal metastases and may be helpful in better identifying suitable candidates for the local excision of early stage rectal cancer. See Video Abstract at http://links.lww.com/DCR/A412. PMID- 28991085 TI - Crohn's Disease of the Pouch: A True Diagnosis or an Oversubscribed Diagnosis of Exclusion? AB - BACKGROUND: After IPAA, 8% of patients with ulcerative colitis are later diagnosed with Crohn's disease of the pouch, associated with an increased rate of pouch failure. No study has reported on how often the clinical diagnosis is correlated with histologic findings of Crohn's disease in the excised pouch. OBJECTIVE: The purpose of this study was to determine whether the clinical diagnosis is consistent with pathologic confirmation at pouch excision. SETTINGS: The study was conducted at a tertiary IBD referral center. PATIENTS: Patients with chronic ulcerative colitis who underwent pouch excision for presumed Crohn's disease of the pouch were included. MAIN OUTCOME MEASURES: Preoperative evaluation and pathologic variables at the time of pouch excision were measured. RESULTS: A total of 35 patients underwent pouch excision for Crohn's disease of the pouch based on a combination of clinical, radiographic, and endoscopic findings. Seven (20%) had surgical pathology consistent with Crohn's disease at pouch excision. There were no differences in those 7 patients and the remaining 28 in terms of diagnosis at colectomy, primary pouch symptoms, prepouch inflammation, ulceration, or granulomas at endoscopy. In the nonpathology confirmed Crohn's disease, 40% (n = 11) had an anastomotic leak at time of IPAA versus 0% in the Crohn's disease group, and 86% (n = 24) had symptoms of pouch dysfunction within 5 months of ileostomy reversal versus 13 months in the Crohn's disease group. Of 28 without pathology-confirmed Crohn's disease, 100% (n = 28) were treated with antibiotics, 68% (n = 19) with steroids, 59% (n = 16) with immunomodulators, and 57% (n = 15) with biologic therapy for Crohn's disease of the pouch. LIMITATIONS: The study was limited by its single-center scope and lack of an established definition for Crohn's disease of the pouch. CONCLUSIONS: Pathologic confirmation of Crohn's disease was given to only one fifth of patients who underwent pouch excision for Crohn's disease of the pouch. Given the histologic variability in Crohn's disease, it may be unreasonable to expect histologic confirmation in every case; still, the diagnosis of Crohn's disease of the pouch may be overly ascribed, resulting in unnecessary immunosuppressive medications and exclusion from consideration for pouch reconstructive surgery. See Video Abstract at http://links.lww.com/DCRA432. PMID- 28991084 TI - Association Among Obesity, Metabolic Health, and the Risk for Colorectal Cancer in the General Population in Korea Using the National Health Insurance Service National Sample Cohort. AB - BACKGROUND: In Korea, the incidence of colorectal cancer has increased and obesity is on a rising trend because of a Westernized lifestyle in men. OBJECTIVE: The purpose of this study was to evaluate the relationship between metabolic health status, as well as BMI, and the incidence of colorectal cancer. DESIGN: This was a prospective cohort study. SETTINGS: The study was conducted with the National Health Insurance Service-National Sample Cohort. PATIENTS: A total of 408,931 Korean adults without cancer at baseline were followed up until 2013 (mean follow-up, 9 y). MAIN OUTCOME MEASURES: Demographic, anthropometric, and laboratory data at baseline were collected and categorized. The presence of diabetes mellitus, hypertension, and dyslipidemia was defined using the criteria of previous studies. The incidence of colorectal cancer was also defined according to the International Classification of Disease, 10 Revision, codes and the claim data on endoscopy with biopsy. RESULTS: During the follow-up, 5108 new cases of colorectal cancer occurred. Being underweight (<18.5 kg/m) reduced the risk for colorectal cancer among women (adjusted HR = 0.646 (95% CI, 0.484 0.863)), whereas high BMI significantly increased the risk in men and in the elderly. Obesity (>=25 kg/m), diabetes mellitus, and hypertension were identified as risk factors for colorectal cancer in men but not for women. Although metabolically unhealthy nonobese men had a higher risk for colorectal cancer than metabolically healthy nonobese men (adjusted HR = 1.114 (95% CI, 1.004-1.236)), the risk was lower than that in the obese men. LIMITATIONS: The study population consisted of people who underwent health examinations, thus there could be selection bias. CONCLUSIONS: In Korean adults, obesity contributes to the incidence of colorectal cancer with a sex difference. Nonobese but metabolically unhealthy men are considered to be a high-risk group for colorectal cancer, but obesity itself is more important in colorectal carcinogenesis. See Video Abstract at http://links.lww.com/DCR/A475. PMID- 28991086 TI - Bowel Dysfunction Related to Spina Bifida: Keep It Simple. AB - BACKGROUND: Although care of urological disorders in spina bifida is well established, there is yet no agreement on a standardized approach to bowel dysfunction in this population. OBJECTIVE: The purpose of this study was to assess bowel dysfunction using validated instruments and the risk factors in adults with spina bifida. DESIGN: A multidisciplinary team prospectively collected patient data, focusing on anorectal and urological symptoms. SETTINGS: The study was conducted with data from a French referral center for spina bifida. PATIENTS: A total of 228 adults with spina bifida (sex ratio men:women, 92 (40%):136 (60%)) with a median age of 34.7 years (range, 26.8-44.7 y) were assessed. MAIN OUTCOMES MEASURES: Factors associated with severe fecal incontinence (Cleveland Clinic Incontinence Score >=9) and severe bowel dysfunction (Neurogenic Bowel Dysfunction score >=14) were assessed in a multivariate analysis model. RESULTS: The prevalence rates of severe fecal incontinence and severe bowel dysfunction were 60% (130/217) and 42% (71/168). Bowel dysfunction was the second most common major concern of patients after lower urinary tract dysfunction. Male sex, obesity, urinary incontinence, and a Knowles-Eccersley-Scott symptom constipation score >=10 were independently associated with severe fecal incontinence. Patients with soft stools had significantly less severe bowel dysfunction. Neither neurologic level nor other neurologic features of spina bifida were associated with severe fecal incontinence or severe bowel dysfunction. LIMITATIONS: The recruitment of patients with spina bifida through a national referral center might have resulted in selection bias, and some data were missing especially regarding BMI and Neurogenic Bowel Dysfunction score (21% and 26% of missing data). CONCLUSIONS: The prevalence rates of severe fecal incontinence and severe bowel dysfunction in adults with spina bifida were high and were adequately perceived by the patients. The present study emphasized the association of bowel dysfunction and fecal incontinence with obesity, urologic disorders, and stool consistency rather than neurologic features. See Video Abstract at http://links.lww.com/DCR/A394. PMID- 28991087 TI - Robot-Assisted Ventral Mesh Rectopexy for Rectal Prolapse: A 5-Year Experience at a Tertiary Referral Center. AB - BACKGROUND: Laparoscopic ventral mesh rectopexy is being increasingly performed internationally to treat rectal prolapse syndromes. Robotic assistance appears advantageous for this procedure, but literature regarding robot-assisted ventral mesh rectopexy is limited. OBJECTIVE: The primary objective of this study was to assess the safety and effectiveness of robot-assisted ventral mesh rectopexy in the largest consecutive series of patients to date. DESIGN: This study is a retrospective cross-sectional analysis of prospectively collected data. SETTINGS: The study was conducted in a tertiary referral center. PATIENTS: All of the patients undergoing robot-assisted ventral mesh rectopexy for rectal prolapse syndromes between 2010 and 2015 were evaluated. MAIN OUTCOME MEASURES: Preoperative and postoperative (mesh and nonmesh) morbidity and functional outcome were analyzed. The actuarial recurrence rates were calculated using the Kaplan-Meier method. RESULTS: A total of 258 patients underwent robot-assisted ventral mesh rectopexy (mean +/- SD follow-up = 23.5 +/- 21.8 mo; range, 0.2 - 65.1 mo). There were no conversions and only 5 intraoperative complications (1.9%). Mortality (0.4%) and major (1.9%) and minor (<30 d) early morbidity (7.0%) were acceptably low. Only 1 (1.3%) mesh-related complication (asymptomatic vaginal mesh erosion) was observed. A significant improvement in obstructed defecation (78.6%) and fecal incontinence (63.7%) were achieved for patients (both p < 0.0005). At final follow-up, a new onset of fecal incontinence and obstructed defecation was induced or worsened in 3.9% and 0.4%. The actuarial 5 year external rectal prolapse and internal rectal prolapse recurrence rates were 12.9% and 10.4%. LIMITATIONS: This was a retrospective study including patients with minimal follow-up. No validated scores were used to assess function. The study was monocentric, and there was no control group. CONCLUSIONS: Robot assisted ventral mesh rectopexy is a safe and effective technique to treat rectal prolapse syndromes, providing an acceptable recurrence rate and good symptomatic relief with minimal morbidity. See Video Abstract at http://links.lww.com/DCR/A427. PMID- 28991088 TI - Totally Laparoscopic Retroileal Transverse Colon to Rectal Anastomosis Following Extended Left Colectomy. PMID- 28991089 TI - Retained Needle Following Transanal Hemorrhoidal Dearterialization. AB - INTRODUCTION: A needle was retained during transanal hemorrhoidal dearterialization. This rare complication has not been described before. TECHNIQUE: A spinal needle was inserted from the perianal skin to localize the retained foreign body that was located at 7 cm from the anal margin. A decision was made to proceed to intersphincteric dissection, and a 3-cm incision was made in the perianal skin from 2 to 4 o'clock. Deep pararectal dissection continued, and the needle was eventually found lying in the muscular layer, parallel to the plane of the dissection. RESULTS: The needle was retrieved intact, and repeat x ray confirmed that no foreign body was retained. The patient made an uneventful recovery and was discharged home on postoperative day 1 with a 5-day course of oral antibiotics; she was examined in clinic 4 weeks following surgery and reported significant symptomatic improvement with no perianal pain or rectal bleeding. No anal fistula was found on the examination. CONCLUSIONS: X-ray guidance is a helpful adjunct to facilitate 3-dimensional localization. Intersphincteric dissection is a reliable alternative to the transanal approach, particularly when the needle cannot be seen arising from the mucosa or felt on palpation. Repeated attempts to palpate the needle should be avoided, because there is a potential risk of displacing it deeper or higher, making retrieval more difficult. PMID- 28991090 TI - Single-Incision Laparoscopic Colectomy with Complete Mesocolic Excision Versus Multiport Laparoscopic Colectomy for Colon Cancer. PMID- 28991091 TI - The Author Replies. PMID- 28991092 TI - Ileostomy Reversal: Length of Stay Can Be Safely Decreased Further to Same-Day Discharge in Many. PMID- 28991093 TI - The Authors Reply. PMID- 28991097 TI - Reflections on 50 Years of Neuroscience Nursing: Publication Trends in Neurotrauma. AB - In 2018, the American Association of Neuroscience Nurses will celebrate its 50th anniversary as the premier member organization for neuroscience nurses. In recent decades, one of the highest rated member benefits has been the ability for members to join special focus groups (SFGs). The SFGs were initiated to allow an avenue for information sharing and communication for neuroscience nurses in a variety of subspecialties. In this anniversary edition, the neurotrauma SFG presents a review of trends in the publication of articles in the Journal of Neuroscience Nursing related to neurotrauma. Findings from this article illustrate how these publications have impacted the nursing care of patients who have sustained traumatic injuries of the central and peripheral nervous system and the integral role of neuroscience nurses throughout the decades. PMID- 28991098 TI - Five-Year-Old Boy With Behavioral Changes and Papilledema. AB - A 5-year-old boy had initial symptoms of behavioral changes, nausea, vomiting, headache, weight loss, and progressive vision failure. Brain MRI revealed abnormal signal intensity in both optic nerves, the optic chiasm, the right medial temporal lobe, and tissues surrounding the right supraclinoid internal carotid artery with associated leptomeningeal and spinal cord enhancement. After nondiagnostic dural and spinal arachnoid biopsies, a temporal lobe biopsy was diagnostic for a rare malignant peripheral nerve sheath tumor. PMID- 28991096 TI - Evaluation of Intervention Fidelity in a Multisite Clinical Trial in Persons With Multiple Sclerosis. AB - BACKGROUND: Careful consideration of intervention fidelity is critical to establishing the validity and reliability of research findings, yet such reports are often lacking in the research literature. It is imperative that intervention fidelity be methodically evaluated and reported to promote the translation of effective interventions into sound evidence-based practice. PURPOSE: The purpose of this article is to explore strategies used to promote intervention fidelity, incorporating examples from a multisite clinical trial, that illustrate the National Institutes of Health Behavior Change Consortium's 5 domains for recommended treatment practices: (1) study design, (2) facilitator training, (3) intervention delivery, (4) intervention receipt, and (5) intervention enactment. A multisite randomized clinical trial testing the efficacy of a computer-assisted cognitive rehabilitation intervention for adults with multiple sclerosis is used to illustrate strategies promoting intervention fidelity. METHODS: Data derived from audiotapes of intervention classes, audits of computer exercises completed by participants, participant class attendance, and goal attainment scaling suggested relatively high fidelity to the intervention protocol. CONCLUSION: This study illustrates how to report intervention fidelity in the literature guided by best practice strategies, which may serve to promote fidelity monitoring and reporting in future studies. PMID- 28991099 TI - Nonsurgical Management of Retained Needlefish Jaw. AB - While scuba diving, the left medial canthus of a 53-year-old man was pierced by a needlefish. He immediately lost vision in his left eye. An orbital computed tomographic scan showed the needlefish jaw in the left optic canal. The left medial orbit was explored surgically but no foreign object was removed. One month later, MRI confirmed the presence of the retained needlefish jaw. A conservative approach was taken and the patient remained stable over 3 months of follow-up. PMID- 28991100 TI - Laughter-Induced Transient Vision Loss in a Patient With Silent Sinus Syndrome. AB - BACKGROUND: To report a patient with silent sinus syndrome (SSS) who experienced transient ipsilateral monocular vision loss during intense laughter. METHODS: Case report. RESULTS: Our patient's transient vision loss completely resolved after maxillary sinus decompression and during 7 months of follow-up. CONCLUSIONS: Although the precise mechanism of our patient's vision loss remains undetermined, we suspect that the vascular supply to the eye and/or the optic nerve was compromised as the result of the combination of laughter (causing Valsalva maneuver and increased intrathoracic pressure) and SSS. PMID- 28991101 TI - Why a One-Way Ticket to Mars May Result in a One-Way Directional Glymphatic Flow to the Eye. PMID- 28991102 TI - Why a One-Way Ticket to Mars May Result in One-Way Directional Glymphatic Flow to the Eye: Response. PMID- 28991103 TI - Clinical and Oculographic Analysis of Inferior Oblique Myokymia. AB - A 63-year-old man experienced transient vertical oscillopsia lasting several seconds for 2 months. Examination disclosed paroxysmal excyclotorsion of the right eye, spontaneously or triggered by adduction. Eye movements using 3D video oculography showed intermittent, monocular phasic movements which consisted of excyclotorsion of the right eye mixed with a small amount of supraduction and abduction, and a tonic movement with excyclotorsion and slight elevation. Orbital and brain MRI was unremarkable. Administration of oxcarbazepine markedly decreased the severity and frequency of the episodes. The oculographic characteristics in our patient may indicate that inferior oblique myokymia may be attributed to aberrant, spontaneous discharges in the inferior oblique motor unit. PMID- 28991104 TI - International Consensus Statement on the Clinical and Therapeutic Management of Leber Hereditary Optic Neuropathy. AB - Leber hereditary optic neuropathy (LHON) is currently estimated as the most frequent mitochondrial disease (1 in 27,000-45,000). Its molecular pathogenesis and natural history is now fairly well understood. LHON also is the first mitochondrial disease for which a treatment has been approved (idebenone-Raxone, Santhera Pharmaceuticals) by the European Medicine Agency, under exceptional circumstances because of the rarity and severity of the disease. However, what remains unclear includes the optimal target population, timing, dose, and frequency of administration of idebenone in LHON due to lack of accepted definitions, criteria, and general guidelines for the clinical management of LHON. To address these issues, a consensus conference with a panel of experts from Europe and North America was held in Milan, Italy, in 2016. The intent was to provide expert consensus statements for the clinical and therapeutic management of LHON based on the currently available evidence. We report the conclusions of this conference, providing the guidelines for clinical and therapeutic management of LHON. PMID- 28991105 TI - Low-dose Aspirin Inhibits Cardiac Sympathetic Activation and Vagal Withdrawal Response to Morning Rising. AB - Aspirin is known to interfere with platelet function and can protect individuals at risk of sudden death. However, this property of aspirin is less defined for cardiac autonomic activity. We assessed pulse rate variability by spectral analysis and measured plasma eicosanoid levels before and after administration of 81-mg aspirin to 12 healthy subjects over a 60-degree head-up tilt test in the morning. In upright posture, low-dose aspirin decreased both the normalized unit value of low-frequency (normalized LF) power (mean +/- SD, 82.5 +/- 4.5 vs. 77.5 +/- 6.5 nu, P = 0.01) and LF/HF ratio (6.0 +/- 2.1 vs. 4.7 +/- 2.7, P = 0.02) and augmented the normalized unit value of high-frequency power (15.0 +/- 4.4 vs. 19.8 +/- 6.4 nu, P = 0.004). It simultaneously upregulated plasma 6-keto PGF1alpha level (13.4 +/- 6.8 vs. 19.7 +/- 12.8 pg/mL, P = 0.04) and inhibited plasma thromboxane B2 (TXB2) level (11.6 +/- 7.3 vs. 6.3 +/- 4.2 pg/mL, P = 0.003). In the upright posture, both before and after aspirin, there was a significant direct correlation between plasma TXB2 levels and the normalized LF power (r = 0.42, P = 0.04) as well as between the plasma TXB2/6-keto-PGF1alpha ratio and the normalized LF power (r = 0.50, P = 0.01). Administration of low dose aspirin in healthy people inhibits cardiac sympathetic activation and vagal withdrawal response to morning rising through an alternation of the TXA2/PGI2 balance. PMID- 28991106 TI - Pharmacological Therapies for Hepatorenal Syndrome: A Systematic Review and Meta Analysis. AB - BACKGROUND: Hepatorenal syndrome (HRS) is a serious complication of advanced chronic liver disease. Different pharmacological therapies have variable efficacy. We performed a systematic review and meta-analysis to compare the efficacy of various drugs in the treatment of HRS. STUDY: Randomized controlled trials comparing active drug with placebo or comparing 2 different drugs were included in this analysis. Primary study outcome was reversal of HRS. Secondary outcomes were HRS relapse and patient survival. Subgroup analysis was performed on patients with type 1 HRS. RESULTS: Thirteen randomized controlled trial were eligible for analysis. Terlipressin plus albumin was more efficacious than placebo plus albumin (odds ratio=4.72; 95% confidence interval, 1.72-12.93; P=0.003) or midodrine plus albumin and octreotide (odds ratio=5.94; 95% confidence interval, 1.69-20.85; P=0.005), for HRS reversal. However, no significant difference was noted comparing terlipressin plus albumin versus noradrenaline plus albumin, octreotide plus albumin versus placebo plus albumin or noradrenaline plus albumin versus midodrine plus albumin and octreotide. None of the comparisons showed difference on HRS relapse or patient survival. Subgroup analysis revealed that terlipressin was more effective than placebo for type 1 HRS reversal, but no significant differences were noted between any other comparisons, and none of the comparisons showed difference on HRS relapse or patient survival. CONCLUSIONS: Intravenous infusion of terlipressin is the most effective medical therapy for reversing HRS. Intravenous infusion of noradrenaline is an acceptable alternative. Studies are needed as basis for developing pharmacological strategies to reduce relapse of HRS and improve patient survival. PMID- 28991107 TI - Discontinuation of Biological Treatments in Inflammatory Bowel Disease: A Concise Pragmatic Review. AB - Despite the proven efficacy of biological drugs for inflammatory bowel disease, these therapies are costly and do carry some risks, providing incentive for exploring strategies to discontinue therapy in patients with prolonged remission. We presently review multiple cohort studies indicating the overall risk of relapse after stopping an anti-tumor necrosis factor (TNF) in inflammatory bowel disease patients is roughly 40% at 12 months after therapy cessation. Despite methodological differences across studies, it appears that patients without deep remission (ie, patients with endoscopic or biomarker evidence of inflammation) are at increased risk of relapse after stopping anti-TNF, as are those with high adequate levels of anti-TNF before stopping. In patients who relapse after anti TNF cessation, retreatment with the same biological seems to reinduce clinical response in most patients. Immunological reasons responsible for this high success rate for retreatment are elucidated, but resorting to retreatment also implies a small but finite risk of a severe flare leading to surgery, which should be borne in mind. Thus, stopping attempts should probably be reserved for patients with low risk for severe outcome should a relapse occur. Proactive endoscopic monitoring after drug cessation is imperative to reduce these risks. The recently introduced concept of treatment-cycles is discussed, along with a pragmatic algorithm of decision tree for therapy discontinuation in the selected appropriate patients. PMID- 28991108 TI - Patient Harm in Cataract Surgery: A Series of Adverse Events in Massachusetts. AB - Massachusetts state agencies received reports of 37 adverse events (AEs) involving cataract surgery from 2011 to 2015. Fifteen were anesthesia related, including 5 wrong eye blocks, 3 cases of hemodynamic instability, 2 retrobulbar hematoma/hemorrhages, and 5 globe perforations resulting in permanent loss of vision. While Massachusetts' reported AEs likely underrepresent the true number of AEs that occur during cataract surgery, they do offer useful signal data to indicate the types of patient harm occurring during these procedures. PMID- 28991109 TI - Patient Blood Management in Pediatric Cardiac Surgery: A Review. AB - Efforts to reduce blood product transfusions and adopt blood conservation strategies for infants and children undergoing cardiac surgical procedures are ongoing. Children typically receive red blood cell and coagulant blood products perioperatively for many reasons, including developmental alterations of their hemostatic system, and hemodilution and hypothermia with cardiopulmonary bypass that incites inflammation and coagulopathy and requires systemic anticoagulation. The complexity of their surgical procedures, complex cardiopulmonary interactions, and risk for inadequate oxygen delivery and postoperative bleeding further contribute to blood product utilization in this vulnerable population. Despite these challenges, safe conservative blood management practices spanning the pre-, intra-, and postoperative periods are being developed and are associated with reduced blood product transfusions. This review summarizes the available evidence regarding anemia management and blood transfusion practices in the perioperative care of these critically ill children. The evidence suggests that adoption of a comprehensive blood management approach decreases blood transfusions, but the impact on clinical outcomes is less well studied and represents an area that deserves further investigation. PMID- 28991110 TI - Photoplethysmography and Heart Rate Variability for the Diagnosis of Preeclampsia. AB - BACKGROUND: The goal of this study was to determine a set of timing, shape, and statistical features available through noninvasive monitoring of maternal electrocardiogram and photoplethysmography that identifies preeclamptic patients. METHODS: Pregnant women admitted to Labor and Delivery were monitored with pulse oximetry and electrocardiogram for 30 minutes. Photoplethysmogram features and heart rate variability were extracted from each data set and applied to a sequential feature selection algorithm to discriminate women with preeclampsia with severe features, from normotensive and hypertensive controls. The classification boundary was chosen to minimize the expected misclassification cost. The prior probabilities of the misclassification costs were assumed to be equal. RESULTS: Thirty-seven patients with clinically diagnosed preeclampsia with severe features were compared with 43 normotensive controls; all were in early labor or beginning induction. Six variables were used in the final model. The area under the receiver operating characteristic curve was 0.907 (standard error [SE] = 0.004) (sensitivity 78.2% [SE = 0.3%], specificity 89.9% [SE = 0.1%]) with a positive predictive value of 0.883 (SE = 0.001). Twenty-eight subjects with chronic or gestational hypertension were compared with the same preeclampsia group, generating a model with 5 features with an area under the curve of 0.795 (SE = 0.007; sensitivity 79.0% [SE = 0.2%], specificity 68.7% [SE = 0.4%]), and a positive predictive value of 0.799 (SE = 0.002). CONCLUSIONS: Vascular parameters, as assessed noninvasively by photoplethysmography and heart rate variability, may have a role in screening women suspected of having preeclampsia, particularly in areas with limited resources. PMID- 28991111 TI - An Intraplantar Hypertonic Saline Assay in Mice for Rapid Screening of Analgesics. AB - BACKGROUND: Development of new analgesics is limited by shortcomings of existing preclinical screening assays such as wide variations in response, suitability for a narrow range of analgesics, and propensity to induce tissue damage. Our aim was to determine the feasibility of a new in vivo animal assay as an analgesic screen based on nociceptive responses (licking and biting) after intraplantar (i.pl.) injection of hypertonic saline (HS) in mice. METHODS: With approval from the Institutional Animal Care Committee, we conducted a randomized, investigator blinded in vivo study in adult CD-1 mice. We first studied the concentration response relationship, time course, and sex difference of animals' nociceptive responses to HS. Subsequently, we assessed the screening ability of the HS assay to detect a range of established analgesics belonging to different classes. Finally, we performed histopathologic studies to assess potential tissue damage. RESULTS: The response produced by i.pl. HS was greater and longer in female than in male mice. The responses to HS were concentration dependent with minimal variance. Ten percent HS evoked a maximal response within the first 5 minutes. Morphine dose-dependently attenuated animals' nociceptive responses (1-10 mg/kg intraperitoneally [i.p.]). The peripherally restricted u-opioid receptor agonist, loperamide, reduced nociceptive responses when injected locally (30-100 ug/paw, i.pl.) but not systemically (1-10 mg/kg, i.p.). Acetylsalicylic acid (300 mg/kg, i.p.), naproxen (150 mg/kg, i.p), and acetaminophen (300 mg/kg, i.p.) all decreased nociceptive responses, as did i.pl. coinjections of lidocaine (0.003% 1%) with 10% HS. Histopathologic assessment revealed no tissue damage due to HS. CONCLUSIONS: The i.pl. HS assay is easily performed, rapidly detects standard analgesics, and produces minimal animal suffering without tissue damage. We propose this assay as a useful addition to the armamentarium of existing preclinical analgesic screens. PMID- 28991112 TI - The Influence of Age on Sensitivity to Dexmedetomidine Sedation During Spinal Anesthesia in Lower Limb Orthopedic Surgery. AB - To investigate the influence of age on sensitivity to dexmedetomidine sedation in adult patients, we selected 79 patients scheduled for lower limb orthopedic surgery under spinal anesthesia to identify the dexmedetomidine ED50 for adequate sedation among different age groups. After a spinal anesthetic was placed, a dose of dexmedetomidine determined by the Dixon up-and-down method was administered over 15 minutes. The ED50 in the elderly group was lower than in the other 2 groups (elderly: 0.88 +/- 0.07; middle aged: 1.16 +/- 0.08; young: 1.21 +/- 0.06 ug/kg; both P < .001). There was no difference between the young and middle-aged groups (P = .160). PMID- 28991113 TI - Pearls of Wisdom for High-Risk Laser Lead Extractions: A Focused Review. AB - Due to new indications and improved technology, the incidence of laser lead extraction (LLE) has significantly increased over the past years. While LLE has been well studied and proven to be safe and effective, only few studies are geared toward the anesthesiologist's role during high-risk LLEs. This article utilized both a focused review and authors' experience to investigate anesthetic protocols during LLEs. Through this review, we recommend best practices for the anesthesiologist including appropriate procedure location, onsite availability of a cardiac surgeon, availability of a cardiopulmonary bypass machine, and intraoperative use of echocardiography to detect and address potential complications during high-risk LLEs. PMID- 28991115 TI - Preventing Adverse Events in Cataract Surgery: Recommendations From a Massachusetts Expert Panel. AB - Massachusetts health care facilities reported a series of cataract surgery related adverse events (AEs) to the state in recent years, including 5 globe perforations during eye blocks performed by 1 anesthesiologist in a single day. The Betsy Lehman Center for Patient Safety, a nonregulatory Massachusetts state agency, responded by convening an expert panel of frontline providers, patient safety experts, and patients to recommend strategies for mitigating patient harm during cataract surgery. The purpose of this article is to identify contributing factors to the cataract surgery AEs reported in Massachusetts and present the panel's recommended strategies to prevent them. Data from state-mandated serious reportable event reports were supplemented by online surveys of Massachusetts cataract surgery providers and semistructured interviews with key stakeholders and frontline staff. The panel identified 2 principal categories of contributing factors to the state's cataract surgery-related AEs: systems failures and choice of anesthesia technique. Systems failures included inadequate safety protocols (48.7% of contributing factors), communication challenges (18.4%), insufficient provider training (17.1%), and lack of standardization (15.8%). Choice of anesthesia technique involved the increased relative risk of needle-based eye blocks. The panel's surveys of Massachusetts cataract surgery providers show wide variation in anesthesia practices. While 45.5% of surgeons and 69.6% of facilities reported increased use of topical anesthesia compared to 10 years earlier, needle-based blocks were still used in 47.0% of cataract surgeries performed by surgeon respondents and 40.9% of those performed at respondent facilities. Using a modified Delphi approach, the panel recommended several strategies to prevent AEs during cataract surgery, including performing a distinct time-out with at least 2 care-team members before block administration; implementing standardized, facility-wide safety protocols, including a uniform site-marking policy; strengthening the credentialing and orientation of new, contracted and locum tenens anesthesia staff; ensuring adequate and documented training in block administration for any provider who is new to a facility, including at least 10 supervised blocks before practicing independently; using the least invasive form of anesthesia appropriate to the patient; and finally, adjusting anesthesia practices, including preferred techniques, as evidence-based best practices evolve. Future research should focus on evaluating the impact of these recommendations on patient outcomes. PMID- 28991114 TI - A Survey Evaluating Burnout, Health Status, Depression, Reported Alcohol and Substance Use, and Social Support of Anesthesiologists. AB - BACKGROUND: Burnout affects all medical specialists, and concern about it has become common in today's health care environment. The gold standard of burnout measurement in health care professionals is the Maslach Burnout Inventory-Human Services Survey (MBI-HSS), which measures emotional exhaustion, depersonalization (DP), and personal accomplishment. Besides affecting work quality, burnout is thought to affect health problems, mental health issues, and substance use negatively, although confirmatory data are lacking. This study evaluates some of these effects. METHODS: In 2011, the American Society of Anesthesiologists and the journal Anesthesiology cosponsored a webinar on burnout. As part of the webinar experience, we included access to a survey using MBI-HSS, 12-item Short Form Health Survey (SF-12), Social Support and Personal Coping (SSPC-14) survey, and substance use questions. Results were summarized using sample statistics, including mean, standard deviation, count, proportion, and 95% confidence intervals. Adjusted linear regression methods examined associations between burnout and substance use, SF-12, SSPC-14, and respondent demographics. RESULTS: Two hundred twenty-one respondents began the survey, and 170 (76.9%) completed all questions. There were 266 registrants total (31 registrants for the live webinar and 235 for the archive event), yielding an 83% response rate. Among respondents providing job titles, 206 (98.6%) were physicians and 2 (0.96%) were registered nurses. The frequency of high-risk responses ranged from 26% to 59% across the 3 MBI-HSS categories, but only about 15% had unfavorable scores in all 3. Mean mental composite score of the SF-12 was 1 standard deviation below normative values and was significantly associated with all MBI-HSS components. With SSPC-14, respondents scored better in work satisfaction and professional support than in personal support and workload. Males scored worse on DP and personal accomplishment and, relative to attending physicians, residents scored worse on DP. There was no significant association between MBI-HSS and substance use. CONCLUSIONS: Many anesthesiologists exhibit some high-risk burnout characteristics, and these are associated with lower mental health scores. Personal and professional support were associated with less emotional exhaustion, but overall burnout scores were associated with work satisfaction and professional support. Respondents were generally economically satisfied but also felt less in control at work and that their job kept them from friends and family. The association between burnout and substance use may not be as strong as previously believed. Additional work, perhaps with other survey instruments, is needed to confirm our results. PMID- 28991116 TI - Incidence and Operative Factors Associated With Discretional Postoperative Mechanical Ventilation After General Surgery. AB - BACKGROUND: Mechanical ventilation after general surgery is associated with worse outcomes, prolonged hospital stay, and increased health care cost. Postoperatively, patients admitted to the intensive care unit (ICU) may be categorized into 1 of 3 groups: extubated patients (EXT), patients with objective medical indications to remain ventilated (MED), and patients not meeting these criteria, called "discretional postoperative mechanical ventilation" (DPMV). The objectives of this study were to determine the incidence of DPMV in general surgery patients and identify the associated operative factors. METHODS: At a large, tertiary medical center, we reviewed all surgical cases performed under general anesthesia from April 1, 2008 to February 28, 2015 and admitted to the ICU postoperatively. Patients were categorized into 1 of 3 cohorts: EXT, MED, or DPMV. Operative factors related to the American Society of Anesthesiologists Physical Status (ASA PS), duration of surgery, surgery end time, difficult airway management, intraoperative blood and fluid administration, vasopressor infusions, intraoperative arterial blood gasses, and ventilation data were collected. Additionally, anesthesia records were reviewed for notes indicating a reason or rationale for postoperative ventilation. Categorical variables were compared by chi test, and continuous variables by analysis of variance or Kruskal-Wallis H test. Categorical variables are presented as n (%), and continuous variables as mean +/- standard deviation or median (interquartile range) as appropriate. Significance level was set at P<= .05. RESULTS: Sixteen percent of the 3555 patients were categorized as DPMV and 12.2% as MED. Compared to EXT patients, those classified as DPMV had received significantly less fluid (2757 +/- 2728 mL vs 3868 +/- 1885 mL; P < .001), lost less blood during surgery (150 [20-625] mL vs 300 [150-600] mL; P< .001), underwent a shorter surgery (199 +/- 215 minutes vs 276 +/- 143 minutes; P< .001), but received more blood products, 900 (600 1800) mL vs 600 (300-900) mL. The DPMV group had more patients with high ASA PS (ASA III-V) than the EXT group: 508 (90.4%) vs 1934 (75.6%); P< .001. Emergency surgery (ASA E modifier) was more common in the DPMV group than the EXT group: 145 (25.8%) vs 306 (12%), P< .001, respectively. Surgery end after regular working hours was not significantly higher with DPMV status compared to EXT. DPMV cohort had fewer cases with difficult airway when compared to EXT or MED. When compared to MED patients, those classified as DPMV received less fluid (2757 +/- 2728 mL vs 4499 +/- 2830 mL; P< .001), lost less blood (150 [20-625] mL vs 500 [200-1350] mL; P < .001), but did not differ in blood products transfused or duration of surgery. CONCLUSIONS: In our tertiary medical center, patients often admitted to the ICU on mechanical ventilation without an objective medical indication. When compared to patients admitted to the ICU extubated, those mechanically ventilated but without an objective indication had a higher ASA PS class and were more likely to have an ASA E modifier. A surgery end time after regular working hours or difficult airway management was not associated with higher incidence of DPMV. PMID- 28991117 TI - Thermal A-delta Nociceptors, Identified by Transcriptomics, Express Higher Levels of Anesthesia-Sensitive Receptors Than Thermal C-Fibers and Are More Suppressible by Low-Dose Isoflurane. AB - We investigated the effect of isoflurane on 2 main types of thermal nociceptors: A-delta and C-fibers. Surprisingly, 1% inhaled isoflurane led to a hyperalgesic response to C-fiber thermal stimulation, whereas responses to A-delta thermal stimulation were blunted. We explored the hypothesis that differences in withdrawal behavior are mediated by differential expression of isoflurane sensitive proteins between these types of thermal nociceptors. Multiple transcriptomic databases of peripheral neurons were integrated to reveal that isoflurane-susceptible proteins Htr3a, Kcna2, and Scn8a were enriched in thermosensitive A-delta neurons. This exploratory analysis highlights the differing role that volatile anesthetics might have on nociceptors in the peripheral nervous system. PMID- 28991118 TI - Truncated MU-Opioid Receptors With 6 Transmembrane Domains Are Essential for Opioid Analgesia. AB - BACKGROUND: Most clinical opioids act through MU-opioid receptors. They effectively relieve pain but are limited by side effects, such as constipation, respiratory depression, dependence, and addiction. Many efforts have been made toward developing potent analgesics that lack side effects. Three-iodobenzoyl 6beta-naltrexamide (IBNtxA) is a novel class of opioid active against thermal, inflammatory, and neuropathic pain, without respiratory depression, physical dependence, and reward behavior. The MU-opioid receptor (OPRM1) gene undergoes extensive alternative precursor messenger ribonucleic acid splicing, generating multiple splice variants that are conserved from rodents to humans. One type of variant is the exon 11 (E11)-associated truncated variant containing 6 transmembrane domains (6TM variant). There are 5 6TM variants in the mouse OPRM1 gene, including mMOR-1G, mMOR-1M, mMOR-1N, mMOR-1K, and mMOR-1L. Gene-targeting mouse models selectively removing 6TM variants in E11 knockout (KO) mice eliminated IBNtxA analgesia without affecting morphine analgesia. Conversely, morphine analgesia is lost in an exon 1 (E1) KO mouse that lacks all 7 transmembrane (7TM) variants but retains 6TM variant expression, while IBNtxA analgesia remains intact. Elimination of both E1 and E11 in an E1/E11 double KO mice abolishes both morphine and IBNtxA analgesia. Reconstituting expression of the 6TM variant mMOR-1G in E1/E11 KO mice through lentiviral expression rescued IBNtxA but not morphine analgesia. The aim of this study was to investigate the effect of lentiviral expression of the other 6TM variants in E1/E11 KO mice on IBNtxA analgesia. METHODS: Lentiviruses expressing 6TM variants were packaged in HEK293T cells, concentrated by ultracentrifugation, and intrathecally administered 3 times. Opioid analgesia was determined using a radiant-heat tail flick assay. Expression of lentiviral 6TM variant messenger ribonucleic acids was examined by polymerase chain reaction (PCR) or quantitative PCR. RESULTS: All the 6TM variants restored IBNtxA analgesia in the E1/E11 KO mouse, while morphine remained inactive. Expression of lentiviral 6TM variants was confirmed by PCR or quantitative PCR. IBNtxA median effective dose values determined from cumulative dose-response studies in the rescued mice were indistinguishable from wild-type animals. IBNtxA analgesia was maintained for up to 33 weeks in the rescue mice and was readily antagonized by the opioid antagonist levallorphan. CONCLUSIONS: Our study demonstrated the pharmacological relevance of mouse 6TM variants in IBNtxA analgesia and established that a common functional core of the receptors corresponding to the transmembrane domains encoded by exons 2 and 3 is sufficient for activity. Thus, 6TM variants offer potential therapeutic targets for a distinct class of analgesics that are effective against broad-spectrum pain models without many side effects associated with traditional opioids. PMID- 28991119 TI - Higher Operating Table for Optimal Needle-Entry Angle and Less Discomfort During Spinal Anesthesia. AB - The aim of this study was to find the optimal table height to facilitate insertion of the spinal needle at a 90 degrees angle and to reduce the anesthesiologist's discomfort. Sixty patients were randomly allocated according to landmarks on the anesthesiologist's body: umbilicus (group U), lowest rib margin (R), xiphoid process (X), and nipple (N). The coronal insertion angle between the patient's skin and the spinal needle was obtuse in groups U and R, and 90 degrees in group X. We demonstrated that high operating tables at the xiphoid and nipple level facilitate more optimal needle entry angles while reducing the discomfort and joint flexion of anesthesiologists during spinal anesthesia. PMID- 28991120 TI - "Difficult Airway" Bibliometrics: Importance of Capturing the Correct Literature. PMID- 28991122 TI - Peripheral Nerve Blocks for Hip Fractures: A Cochrane Review. AB - BACKGROUND: This review focuses on the use of peripheral nerve blocks as preoperative analgesia, as postoperative analgesia, or as a supplement to general anesthesia for hip fracture surgery and tries to determine if they offer any benefit in terms of pain on movement at 30 minutes after block placement, acute confusional state, myocardial infarction/ischemia, pneumonia, mortality, time to first mobilization, and cost of analgesic. METHODS: Trials were identified by computerized searches of Cochrane Central Register of Controlled Trials (2016, Issue 8), MEDLINE (Ovid SP, 1966 to 2016 August week 1), Embase (Ovid SP, 1988 to 2016 August week 1), and the Cumulative Index to Nursing and Allied Health Literature (EBSCO, 1982 to 2016 August week 1), trials registers, and reference lists of relevant articles. Randomized controlled trials involving the use of nerve blocks as part of the care for hip fractures in adults aged 16 years and older were included. The quality of the studies was rated according to the Cochrane tool. Two authors independently extracted the data. The quality of evidence was judged according to the Grading of Recommendations, Assessment, Development, and Evaluations Working Group scale. RESULTS: Based on 8 trials with 373 participants, peripheral nerve blocks reduced pain on movement within 30 minutes of block placement: standardized mean difference, -1.41 (95% confidence interval [CI], -2.14 to -0.67; equivalent to -3.4 on a scale from 0 to 10; I statistic = 90%; high quality of evidence). The effect size was proportional to the concentration of local anesthetic used (P < .00001). Based on 7 trials with 676 participants, no difference was found in the risk of acute confusional state: risk ratio, 0.69 (95% CI, 0.38-1.27; I statistic = 48%; very low quality of evidence). Based on 3 trials with 131 participants, the risk for pneumonia was decreased: risk ratio, 0.41 (95% CI, 0.19-0.89; I statistic = 3%; number needed to-treat for additional beneficial outcome, 7 [95% CI, 5-72]; moderate quality of evidence). No difference was found for the risk of myocardial ischemia or death within 6 months but the number of participants included was well below the optimum information size for these 2 outcomes. Based on 2 trials with 155 participants, peripheral nerve blocks also reduced the time to first mobilization after surgery: mean difference, -11.25 hours (95% CI, -14.34 to -8.15 hours; I statistic = 52%; moderate quality of evidence). From 1 trial with 75 participants, the cost of analgesic drugs when used as a single-shot block was lower: standardized mean difference, -3.48 (95% CI, -4.23 to -2.74; moderate quality of evidence). CONCLUSIONS: There is high-quality evidence that regional blockade reduces pain on movement within 30 minutes after block placement. There is moderate quality of evidence for a decreased risk of pneumonia, reduced time to first mobilization, and reduced cost of analgesic regimen (single-shot blocks). PMID- 28991123 TI - In Response. PMID- 28991125 TI - Congenital Methemoglobinemia: It is Time for National Level Registry System. PMID- 28991124 TI - Angiogenesis in the Transplanted Donor Graft After Living-Donor Liver Transplantation. AB - BACKGROUND: There is no direct evidence for the role of angiogenesis in liver regeneration in humans. This study aimed to determine whether angiogenesis is involved in the regeneration of transplanted donor grafts in human living-donor liver transplantation (LDLT) and to examine the impact of donor graft volume on angiogenesis. METHODS: Clinical data and liver tissue characteristics were analyzed in 4 patients who received adult-to-adult LDLT with dual left lobe grafts from 2 living donors. Liver tissues from transplanted donor grafts were obtained and immunohistochemically examined at 3 to 4 weeks after transplantation using the endothelial marker Ki67+ and CD31+. RESULTS: All recipients showed recovery of normal liver function and a significant increase in the volume of engrafted left lobes after transplantation. Immunohistochemistry showed a remarkable increase in Ki67+ single hepatocyte proliferation, implying the role of hepatocytes in liver reconstitution, and a high density of blood vessels and proliferative endothelium, suggesting in vivo angiogenesis. Furthermore, we found that Ki67+ nuclei in CD31+ sinusoidal endothelial cells were higher in recipients with smaller donor grafts than in those with larger donor grafts. CONCLUSIONS: Our results suggested that angiogenesis is involved in the regeneration of transplanted liver in humans in inverse proportion to the donor graft volume. PMID- 28991126 TI - Successful Treatment of Invasive Conidiobolus Infection During Therapy for Acute Lymphoblastic Leukemia. AB - Invasive fungal infections are a serious cause of morbidity and mortality in patients with hematologic malignancies. Conidiobolus species are molds within the order Entomophthorales and may disseminate to become rapidly fatal in immunocompromised individuals. This species of fungal infections are often multidrug resistant (MDR) and present unique therapeutic challenges. Reports of Conidiobolus infections are rare in pediatric oncology. We report the successful treatment of an adolescent male with B-cell lymphoblastic leukemia and MDR invasive sinopulmonary Conidiobolus infection with emphasis on early and aggressive neutrophil support with surgical debridement. The strategies described could be applied to other MDR fungal infections. PMID- 28991127 TI - Safe Use of Low-Molecular-weight Heparin in Pediatric Acute Lymphoblastic Leukemia and Lymphoma Around Lumbar Punctures. AB - Children with acute lymphoblastic leukemia or lymphoma (ALL) undergo multiple lumbar punctures (LPs) and frequently require low-molecular-weight heparin (LMWH) for thromboembolic complications. We evaluated if withholding LMWH 24 hours before and after LPs prevented bleeding complications. Children (n=133) with ALL from who were: (1) treated at St. Jude Children's Research Hospital, (2) received LMWH (2*/day of ~1 mg/kg) between January 2004 until December 2012, and (3) underwent a LP were analyzed. Spinal hematoma was defined as a clinical suspicion leading to diagnostic imaging. Traumatic LP was defined as >=10 red blood cells per microliter of cerebrospinal fluid. In 1708 LPs, no hematomas occurred. For each child treated with LMWH, the probability of experiencing a spinal hematoma during the entire ALL treatment course was 0% (95% confidence interval [CI], 0.0% 2.7%), and in each LP, assuming no intrapatient correlation, the probability of spinal hematoma was 0% (95% CI, 0.0%-0.2%). Traumatic LPs were more common when performed when children were not receiving LMWH therapy (odds ratio [OR], 1.5; 95% CI, 1.1-2.2) which may be explained by clinician optimization of known risk factors for traumatic cerebrospinal fluid before the procedures. Withholding LMWH for 24 hours before and after LPs in children being treated for ALL is safe. PMID- 28991128 TI - Characterizing the Biotinidase Deficiency in a Child When Considering a Possible Disease Association. PMID- 28991130 TI - Autoimmune Lymphoproliferative Syndrome Masquerading as Posttransplant Lymphoproliferative Disorder. AB - We present a case of a 2-year-old female presenting with diffuse lymphadenopathy 2 years following orthotopic heart transplant. Initially, she was diagnosed with posttransplant lymphoproliferative disease based on clinical presentation and pathology and she was treated accordingly. Because of persistent lymphadenopathy following the completion of chemotherapy and new onset of autoimmune cytopenias, repeat flow of the lymph node showed an elevated double negative T-cell population prompting evaluation for autoimmune lymphoproliferative syndrome (ALPS). A complete workup was confirmative of a germline Fas mutation consistent with ALPS-FAS. This case emphasizes the importance of considering ALPS-FAS in a patient with lymphadenopathy of unknown cause. PMID- 28991129 TI - A Heterozygous CFHR3-CFHR1 Gene Deletion in a Pediatric Patient With Transplant associated Thrombotic Microangiopathy Who was Treated With Eculizumab. AB - Complement system dysregulation, such as complement Factor H (CFH) autoantibodies and deletions in CFH-related (CFHR) genes 3 and 1, might cause transplant associated thrombotic microangiopathy (TA-TMA). The use of eculizumab, a terminal complement inhibitor, could be a targeted therapy for TA-TMA. We report a 1-year old girl who developed TA-TMA, just after autologous peripheral blood stem cell transplantation in neuroblastoma therapy. Eculizumab improved TA-TMA. Investigation for the complement alternative pathway showed a heterozygous CFHR3 CFHR1 gene deletion, which is involved in complement activation. The patient might develop TA-TMA as a result of complement regulatory gene mutation. PMID- 28991131 TI - Recurrent Atypical Hemolytic Uremic Syndrome in Children With Acute Lymphoblastic Leukemia Undergoing Maintenance Chemotherapy. AB - Chemotherapy-associated myelosuppression and renal dysfunction is not uncommon during childhood acute lymphoblastic leukemia (ALL) therapy. Here we report 2 cases of atypical hemolytic uremic syndrome (aHUS) presenting with pancytopenia and renal dysfunction that developed during maintenance chemotherapy characterized by hypocomplementemia. Both cases experienced recurrence after resolution of the initial aHUS episode upon resumption of chemotherapy, raising a possible contributory role for chemotherapy in the disease pathogenesis. PMID- 28991132 TI - A New Lease on Life: Preliminary Needs Assessment for the Development of a Survivorship Program for Young Adult Survivors of Cancer in South Texas. AB - Priorities for young adult survivorship care from the survivors' perspective are not well documented. To address this within our patient population, we conducted a multimethod needs assessment of young adult survivors of pediatric, adolescent, and young adult cancer in South Texas to get a better understanding of the ongoing challenges and priorities for their survivorship needs and related services. Participants were 18 to 39 years at the time of the needs assessment and predominately Hispanic. In an online survey, survivors most commonly cited being concerned about their physical and mental health, long-term treatment effects, recurrence, and health insurance issues. Participants stated that they received critical support from family, friends, and medical staff, but they would like to receive additional support from other cancer survivors through peer mentorship opportunities and survivor retreats/social events. PMID- 28991133 TI - Pleuropulmonary Blastoma: A Single-center Case Series of 6 Patients. AB - Pleuropulmonary blastoma (PPB) is a rare malignancy of childhood which when left untreated often shows pathologic progression resulting in a more aggressive neoplasm with an increasingly poor prognosis. Because of this it is important to diagnose and initiate treatment early. However, early stage PPB can appear as a cystic lung lesion on imaging and can be easily misdiagnosed given the rarity of the malignancy. Moreover, current therapeutic guidelines for these lesions are not well established, making treatment decisions and management difficult for clinicians. DICER1 mutations are known to be present in a majority of PPBs with or without a germline mutation and may be part of a familial tumor predisposition syndrome. The clinical, pathologic, and genetic data of 6 patients are summarized here. Two patients with type I PPB and 4 patients with type II PPB underwent surgical and chemotherapeutic treatment and all are alive and without recurrence 1 to 13 years after treatment. With increasing awareness of PPB, it is important for clinicians to consider this malignant entity in the evaluation and treatment of patients presenting with a cystic lung abnormality, especially in cases with a history strongly suggestive of a DICER1 mutation. PMID- 28991134 TI - Isolated Testicular Recurrence of AML in Patients With Chronic GVHD >1 Year Following Allogeneic Stem Cell Transplant. AB - BACKGROUND: Patients with chronic graft-versus-host disease (cGVHD) following allogeneic transplant for myeloid leukemias seem to experience a reduced risk of relapse than comparable patients without cGVHD. It is unclear to what extent extramedullary sites are impacted by a graft-versus-leukemia effect. DESIGN/METHOD: Case Series and review of the literature. RESULTS: We present 2 cases of pediatric patients with Acute Myelogenous Leukemia who developed isolated testicular relapse more than a year following hematopoietic stem cell transplantation despite having had extensive cGVHD. Both patients were off immunosuppression and cGVHD medications when testicular relapse occurred. At time of relapse, these patients were negative for minimal residual disease in the marrow and the marrow contained all donor cells by engraftment studies. No evidence was found for lymphocyte infiltration into the affected testicle in either patient. CONCLUSIONS: Although a reduction of marrow relapse can be appreciated in patients with myeloid leukemias and chronic GVHD, this graft versus-leukemia process may be less robust in extramedullary sites and careful surveillance should be maintained to allow early intervention before overt marrow involvement. PMID- 28991136 TI - Utilization Review in Worker's Compensation: Current Status and Opportunities for Improvement. PMID- 28991135 TI - Activity of Paraoxonase/Arylesterase and Butyrylcholinesterase in Peripheral Blood of Gulf War Era Veterans With Neurologic Symptom Complexes or Post Traumatic Stress Disorder. AB - OBJECTIVE: Two groups of Gulf War era veterans, one exhibiting blurred vision, balance problems/dizziness, tremors/shaking, and speech difficulty and a second group with post-traumatic stress disorder (PTSD), but not the neurologic syndrome, were assessed for organophosphate-detoxifying enzyme paraoxonase/arylesterase (PON1) and its Q/R isoforms, butyrylcholinesterase (BuChE) and its U/A isoforms and cytokines. METHODS: Defibrinated peripheral blood was evaluated for enzymes and cytokines. RESULTS: Trends toward elevation of Th2 cytokines interleukin-4 (IL-4) and IL-13 were observed in subjects with neurologic syndrome. Neither the activities nor isoforms of the enzyme, the neurologic symptoms, nor PTSD had any relationship to wartime deployment to the theater of combat. CONCLUSION: The negative outcomes described above suggest that exposure to organophosphates or other agents normally detoxified by PON1 and BuChE may not have contributed significantly to neurologic components of Gulf War Illness. PMID- 28991139 TI - Re: Mortality of Talc Miners and Millers From Val Chisone, Northern Italy. PMID- 28991140 TI - Response to Letter to the Editor On the Mortality of Talc Miners and Millers From Val Chisone, Northern Italy. PMID- 28991141 TI - Long-term Oncologic Outcome After Laparoscopic Converted or Primary Open Resection for Colorectal Cancer: A Systematic Review of the Literature. AB - PURPOSE: The aim of this study was to critically review the current evidence regarding the oncologic outcomes after laparoscopic converted or open resection for colorectal cancer. MATERIALS AND METHODS: A literature search was performed in Pubmed. Study selection and data acquisition were independently performed by 2 reviewers. RESULTS: The search strategy yielded a total of 746 articles, resulting in 7 studies eligible for inclusion. A total of 9190 (57 to 8307) patients were included in the open and 238 (17 to 56) in the converted group. In none of the studies, differences were found in disease stage between both groups. There were no significant differences between both groups with regard to overall survival, local recurrence and distant metastasis rate. CONCLUSIONS: There is currently insufficient evidence that patients who had a laparoscopic resection for colorectal cancer converted to open surgery have a worse oncologic outcome than patients who were primarily treated by an open approach. PMID- 28991143 TI - The Pitfalls of REBOA: Risk Factors and Mitigation Strategies. AB - ABSTRACT: Despite technological advancements, REBOA is associated with significant risks due to complications of vascular access and ischemia reperfusion. The inherent morbidity and mortality of REBOA is often compounded by coexisting injury and hemorrhagic shock. Additionally, the potential for REBOA related injuries is exaggerated due to the growing number of interventions being performed by providers who have limited experience in endovascular techniques, inadequate resources, minimal training in the technique, and who are performing this maneuver in emergency situations. In an effort to ultimately improve outcomes with REBOA, we sought to compile a list of complications that may be encountered during REBOA usage. To address the current knowledge gap, we assembled a list of anecdotal complications from high-volume REBOA users internationally. More importantly, through a consensus model, we identify contributory factors that may lead to complications and deliberate on how to recognize, mitigate, and manage such events. An understanding of the pitfalls of REBOA and strategies to mitigate their occurrence is of vital importance to optimize patient outcomes. PMID- 28991144 TI - Colon-sparing surgery for Clostridium difficile. AB - : There has been recent evidence from a large multi-center study sponsored by the Eastern Association for the Surgery of Trauma that colon-sparing surgery reduces mortality for patients with severe Clostridium difficile associated disease (CDAD) when compared to total colectomy. Amoebic colitis shares many pathologic and clinical features to CDAD, such as worsening diarrhoea, patchy colonic ulceration and necrosis, toxic megacolon, pseudomembranous colitis, perforation, and death. However, published research regarding amoebic colitis is sparse. Surgical management of amoebic colitis may be required in Low Income Countries, or at the geographical interface between more developed and less developed nations, such as at the United States-Mexican border. The authors propose that until further data are available, evidence from CDAD might be applied to the management of amoebic colitis, and surgeons may wish to consider colon-sparing surgery in this context. Large scale prospective studies are warranted, in order to determine whether this practice is associated with similar improvements in outcomes recently observed with CDAD. TYPE OF ARTICLE: Current opinion LEVEL OF EVIDENCE: Not applicable. PMID- 28991145 TI - Use of sarcopenia to predict risk of mortality after emergency abdominal surgery in elderly patients. PMID- 28991147 TI - Transition to College and Adherence to Prescribed Attention Deficit Hyperactivity Disorder Medication. AB - OBJECTIVE: As youth with attention deficit hyperactivity disorder (ADHD) transition to adulthood, they must learn how to manage their ADHD treatment independently. This may be challenging because many of the skills necessary to adhere to treatment (e.g., organization, planning) are impaired in those with ADHD. Using electronic monitoring, we examine trajectories of adherence to medication in a cohort of college students with ADHD. Further, we examine the effect of transitioning to college and executive functioning on adherence. METHODS: Electronic monitors tracked adherence for 51 undergraduate students with ADHD across an academic semester. Multilevel modeling examined individual trajectories in monthly adherence and the role of transition status and self reported executive functioning on these trajectories. RESULTS: Overall, participants adhered to 53.53% of prescribed doses. Transition status predicted the linear slope in adherence (beta = -8.95, standard error [SE] = 3.61, p < .05), with lower initial adherence among undergraduates transitioning to independence (34.17%) compared with post-transition undergraduates (67.63%; beta = 33.46, SE = 8.00, p < .001). Adherence demonstrated a curvilinear change (beta = -7.23, SE = 1.25, p < .001). It increased from the beginning of the semester to midterms before subsequently declining through the rest of the semester, including during final exams. Executive functioning did not predict adherence (beta = -.10, SE = .02, p = .54). CONCLUSION: Only half of all doses were taken as prescribed. Adolescents transitioning to independence demonstrated the lowest levels of adherence, suggesting that the transition to independence is a high risk period for poor self-management of ADHD. PMID- 28991146 TI - Effect of Caregiver Training on the Neurodevelopment of HIV-Exposed Uninfected Children and Caregiver Mental Health: A Ugandan Cluster-Randomized Controlled Trial. AB - OBJECTIVE: Early childhood development programs typically combine healthy nutrition and cognitive stimulation in an integrated model. We separately delivered these 2 components in a cluster-randomized controlled trial to evaluate their comparative effectiveness in promoting healthy child development and caregiver mental health. This is the first study to do so for HIV-affected children and their infected mothers. METHODS: Two hundred twenty-one HIV-exposed but uninfected child (2-3 years old) and caregiver dyads in 18 geographic clusters in Eastern Uganda were randomized by cluster to receive biweekly individualized sessions of either (1) Mediational Intervention for Sensitizing Caregivers (MISC) training emphasizing cognitive stimulation or (2) Uganda Community Based Association for Child Welfare (UCOBAC) program that delivered health and nutrition training. Children were evaluated at baseline, 6 months, 1 year (training conclusion), and 1-year posttraining with the Mullen Scales of Early Learning (MSEL), the Color-Object Association Test for memory, the Early Childhood Vigilance Test of attention, and the Behavior Rating Inventory of Executive Function (BRIEF-parent). The Caldwell Home Observation for the Measurement of the Environment (HOME) was completed by observers to gauge caregiving quality after training. Caregiver depression/anxiety (Hopkins Symptom Checklist-25) and functionality (list of activities of daily living) were also evaluated. Data collectors were blinded to trial arm assignment. RESULTS: Mediational Intervention for Sensitizing Caregivers resulted in significantly better quality of caregiving compared with UCOBAC midintervention with an adjusted mean difference (MadjDiff) of 2.34 (95% confidence interval [CI]: 1.54 3.15, p < .01), postintervention (MadjDiff = 2.43, 95% CI: 1.61-3.25, p < .01), and at 1-year follow-up (MadjDiff = 2.07, 95% CI: 1.23-2.90, p < .01). MISC caregivers reported more problems on the BRIEF for their child at 1-year posttraining only (p < .01). Caregiving quality (HOME) was significantly correlated with MSEL composite performance 1-year posttraining for both the MISC and the UCOBAC trial arms. Likewise, physical growth was significantly related to child development outcomes even though it did not differ between trial arms. CONCLUSION: Even though MISC demonstrated an advantage of improving caregiving quality, it did not produce better child cognitive outcomes compared with health and nutrition training. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01640561. PMID- 28991148 TI - Recollections of Emotional Abuse and Neglect in Childhood as Risk Factors for Depressive Disorders and the Need for Psychotherapy in Adult Life. AB - Theoretical and empirical works have pointed out that depression comes along with adverse interpersonal experiences in childhood and adult life. The purpose of this study was to explore whether past and current experiences differ in their relevance for depression. A clinical group of 80 psychotherapy patients diagnosed with a depressive disorder was contrasted with a control group of 111 nondepressed patients from somatic facilities. Child abuse, neglect, and adult attachment dimensions were measured with self-report scales. Depression was correlated with emotional abuse, neglect, and attachment anxiety. However, solely emotional abuse and neglect significantly predicted the probability to be in the group of depressed patients, whereas attachment anxiety did not contribute to this prediction. The findings reveal that childhood variables, namely, recollections of emotional traumas, are more closely associated with depression than representations of adult attachment bonds and therefore need special attention in the psychotherapeutic treatment of depressive disorders. PMID- 28991149 TI - Decisional Informatics for Psychosocial Rehabilitation: A Feasibility Pilot on Tailored and Fluid Treatment Algorithms for Serious Mental Illness. AB - This study introduces a computerized clinical decision-support tool, the Fluid Outpatient Rehabilitation Treatment (FORT), that incorporates individual and ever evolving patient needs to guide clinicians in developing and updating treatment decisions in real-time. In this proof-of-concept feasibility pilot, FORT was compared against traditional treatment planning using similar behavioral therapies in 52 adults with severe mental illness attending community-based day treatment. At posttreatment and follow-up, group differences and moderate-to large effect sizes favoring FORT were detected in social function, work readiness, self-esteem, working memory, processing speed, and mental flexibility. Of participants who identified obtaining a General Education Diploma as their goal, 73% in FORT passed the examination compared with 18% in traditional treatment planning. FORT was also associated with higher agency cost effectiveness and a better average benefit-cost ratio, even when considering diagnosis, baseline symptoms, and education. Although the comparison groups were not completely equivalent, the findings suggest computerized decision support systems that collaborate with human decision-makers to personalize psychiatric rehabilitation and address critical decisions may have a role in improving treatment effectiveness and efficiency. PMID- 28991150 TI - Two-year Results After Deep Sclerectomy With Nonabsorbable Uveoscleral Implant (Esnoper-Clip): Surgical Area Analysis Using Anterior Segment Optical Coherence Tomography. AB - PURPOSE: To report 2-year results of deep sclerectomy (DS) with mitomycin C and the uveoscleral implant Esnoper-Clip (AJL Ophthalmics, Alava, Spain), a nonabsorbable hema implant, and the morphologic analysis of the surgical area with anterior segment optical coherence tomography (AS-OCT). MATERIALS AND METHODS: In total, 41 eyes of 41 patients with medically uncontrolled open angle glaucoma who underwent DS with the uveoscleral implant were included in this prospective interventional study. Patients were recruited and selected sequentially. All patients were followed at least for 12 months and 36 of them for 24 months. Absolute success was defined as intraocular pressure (IOP)<=18 mm Hg and >=20% of IOP reduction without topical medication. Relative success was defined with the same criteria but with the addition of any antihypertensive medication. Primary outcomes were IOP decrease in the postoperative stage. Secondary outcomes were number of medication, best-corrected visual acuity changes, rate of goniopuncture, needle revision, and AS-OCT analysis of the bleb area. AS-OCT analysis, using Visante OCT, was performed at 1, 12, and 24 months. RESULTS: Absolute success rate was 68.3% at 12 months and 61.1% at 2 years. Relative success was 78.0% and 71.4%, at 12 and 24 months, respectively. A significant IOP decrease was observed, from 27.3+/-6.3 to 14.9+/-4.4 mm Hg at 12 months and 15.3+/-5.2 mm Hg at 24 months (P<0.001). There was also a significant reduction in the number of medications, dropping from a mean of 2.5 to 0.28 one year and 0.36 two years after the surgery (P<0.001). Main postoperative complications were transient: 4 eyes with seidel phenomenon at 24 hours (10.3%), 3 hyphema (7.7%), and 1 choroidal detachment (2.6%). Mean intrascleral space height, measured by AS-OCT, was 0.78 mm and it showed a significant positive correlation with IOP at 12 months. Neodymium-doped yttrium aluminium garnet laser goniopuncture was performed in 25 eyes (61%) at 12 months and in 27 (66.8%) by 24 months. CONCLUSIONS: DS with the uveoscleral implant is a safe and effective procedure to lower IOP in open angle glaucoma patients. IOP reduction is maintained over 2 years and is correlated to the postoperative height of the intrascleral bleb. Supraciliary implantation reduces intrascleral lake dependency, being a simultaneous drainage alternative to the subconjunctival pathway. PMID- 28991151 TI - Optic Disc Drusen and Family History of Glaucoma-Results of a Patient-directed Survey. AB - PURPOSE: Prospective evaluation of family history (FH) of glaucoma and FH of optic disc drusen (ODD) in patients with sonographically confirmed ODD. PATIENTS AND METHODS: A total of 87 patients with ODD interviewed all their first-degree and second-degree relatives using a detailed questionnaire on whether an ophthalmologist had diagnosed or excluded glaucoma or ocular hypertension (OH). Using a second questionnaire, 62 of these patients also provided information about ODD in their FH. Control groups for FH of glaucoma consisted of 2170 patients with glaucoma or OH evaluated with the same methods and identical questions for FH of glaucoma in a previous study, and of 176 healthy individuals without glaucoma or ODD who were interviewed on family history of glaucoma. RESULTS: Glaucoma in FH was significantly more frequent in patients with ODD with an incidence of 20.7% compared with healthy controls with an incidence of 2.8%, and half as frequent as in glaucoma patients with an incidence of 40%. ODD in FH were found in 9.7% of patients with ODD. CONCLUSIONS: As there is a high frequency of family history of glaucoma in patients with ODD, evaluation of FH of ODD and FH of glaucoma is essential in patients with ODD. Glaucoma in FH of ODD patients requires intraocular pressure monitoring and whenever deemed beneficial timely initiation of intraocular pressure-lowering therapy. PMID- 28991152 TI - Two-Dimensional Capillary Electrophoresis with On-Line Sample Preparation and Cyclodextrin Separation Environment for Direct Determination of Serotonin in Human Urine. AB - An advanced two-dimensional capillary electrophoresis method, based on on-line combination of capillary isotachophoresis and capillary zone electrophoresis with cyclodextrin additive in background electrolyte, was developed for effective determination of serotonin in human urine. Hydrodynamically closed separation system and large bore capillaries (300-800 um) were chosen for the possibility to enhance the sample load capacity, and, by that, to decrease limit of detection. Isotachophoresis served for the sample preseparation, defined elimination of sample matrix constituents (sample clean up), and preconcentration of the analyte. Cyclodextrin separation environment enhanced separation selectivity of capillary zone electrophoresis. In this way, serotonin could be successfully separated from the rest of the sample matrix constituents migrating in capillary zone electrophoresis step so that human urine could be directly (i.e., without any external sample preparation) injected into the analyzer. The proposed method was successfully validated, showing favorable parameters of sensitivity (limit of detection for serotonin was 2.32 ng.mL-1), linearity (regression coefficient higher than 0.99), precision (repeatability of the migration time and peak area were in the range of 0.02-1.17% and 5.25-7.88%, respectively), and recovery (ranging in the interval of 90.0-93.6%). The developed method was applied for the assay of the human urine samples obtained from healthy volunteers. The determined concentrations of serotonin in such samples were in the range of 12.4-491.2 ng.mL 1 that was in good agreement with literature data. This advanced method represents a highly effective, reliable, and low-cost alternative for the routine determination of serotonin as a biomarker in human urine. PMID- 28991154 TI - Self-Taught Learning Based on Sparse Autoencoder for E-Nose in Wound Infection Detection. AB - For an electronic nose (E-nose) in wound infection distinguishing, traditional learning methods have always needed large quantities of labeled wound infection samples, which are both limited and expensive; thus, we introduce self-taught learning combined with sparse autoencoder and radial basis function (RBF) into the field. Self-taught learning is a kind of transfer learning that can transfer knowledge from other fields to target fields, can solve such problems that labeled data (target fields) and unlabeled data (other fields) do not share the same class labels, even if they are from entirely different distribution. In our paper, we obtain numerous cheap unlabeled pollutant gas samples (benzene, formaldehyde, acetone and ethylalcohol); however, labeled wound infection samples are hard to gain. Thus, we pose self-taught learning to utilize these gas samples, obtaining a basis vector theta. Then, using the basis vector theta, we reconstruct the new representation of wound infection samples under sparsity constraint, which is the input of classifiers. We compare RBF with partial least squares discriminant analysis (PLSDA), and reach a conclusion that the performance of RBF is superior to others. We also change the dimension of our data set and the quantity of unlabeled data to search the input matrix that produces the highest accuracy. PMID- 28991155 TI - Flexible Piezoelectric Generators by Using the Bending Motion Method of Direct Grown-PZT Nanoparticles on Carbon Nanotubes. AB - Recently, composite-type nanogenerators (NGs) formed from piezoelectric nanostructures and multi-walled carbon nanotubes (CNTs), have become one of the excellent candidates for future energy harvesting because of their ability to apply the excellent electrical and mechanical properties of CNTs. However, the synthesis of NG devices with a high proportion of piezoelectric materials and a low polymer content, such as of polydimethylsiloxane (PDMS), continues to be problematic. In this work, high-piezoelectric-material-content flexible films produced from Pb(Zr,Ti)O3 (PZT)-atomically-interconnected CNTs and polytetrafluoroethylene (PTFE) are presented. Various physical and chemical characterization techniques are employed to examine the morphology and structure of the materials. The direct growth of the piezoelectric material on the CNTs, by stirring the PZT and CNT mixed solution, results in various positive effects, such as a high-quality dispersion in the polymer matrix and addition of flexoelectricity to piezoelectricity, resulting in the enhancement of the output voltage by an external mechanical force. The NGs repeatedly generate an output voltage of 0.15 V. These results present a significant step toward the application of NGs using piezoelectric nanocomposite materials. PMID- 28991153 TI - Vibrio Pathogens: A Public Health Concern in Rural Water Resources in Sub-Saharan Africa. AB - Members of the Vibrio genus are autochthonous inhabitants of aquatic environments and play vital roles in sustaining the aquatic milieu. The genus comprises about 100 species, which are mostly of marine or freshwater origin, and their classification is frequently updated due to the continuous discovery of novel species. The main route of transmission of Vibrio pathogens to man is through drinking of contaminated water and consumption inadequately cooked aquatic food products. In sub-Saharan Africa and much of the developing world, some rural dwellers use freshwater resources such as rivers for domestic activities, bathing, and cultural and religious purposes. This review describes the impact of inadequately treated sewage effluents on the receiving freshwater resources and the associated risk to the rural dwellers that depends on the water. Vibrio infections remain a threat to public health. In the last decade, Vibrio disease outbreaks have created alertness on the personal, economic, and public health uncertainties associated with the impact of contaminated water in the aquatic environment of sub-Saharan Africa. In this review, we carried out an overview of Vibrio pathogens in rural water resources in Sub-Saharan Africa and the implication of Vibrio pathogens on public health. Continuous monitoring of Vibrio pathogens among environmental freshwater and treated effluents is expected to help reduce the risk associated with the early detection of sources of infection, and also aid our understanding of the natural ecology and evolution of Vibrio pathogens. PMID- 28991156 TI - Baseline Assessment of a Healthy Corner Store Initiative: Associations between Food Store Environments, Shopping Patterns, Customer Purchases, and Dietary Intake in Eastern North Carolina. AB - In 2016, the North Carolina (NC) Legislature allocated $250,000 to the NC Department of Agriculture, to identify and equip small food retailers to stock healthier foods and beverages in eastern NC food deserts (the NC Healthy Food Small Retailer Program, HFSRP). The purpose of this study was to examine associations between food store environments, shopping patterns, customer purchases, and dietary consumption among corner store customers. We surveyed 479 customers in 16 corner stores regarding demographics, food purchased, shopping patterns, and self-reported fruit, vegetable, and soda consumption. We objectively assessed fruit and vegetable consumption using a non-invasive reflection spectroscopy device to measure skin carotenoids. We examined associations between variables of interest, using Pearson's correlation coefficients and adjusted linear regression analyses. A majority (66%) of participants were African American, with a mean age of 43 years, and a mean body mass index (BMI) of 30.0 kg/m2. There were no significant associations between the healthfulness of food store offerings, customer purchases, or dietary consumption. Participants who said they had purchased fruits and vegetables at the store previously reported higher produce intake (5.70 (4.29) vs. 4.60 (3.28) servings per day, p = 0.021) versus those who had not previously purchased fresh produce. The NC Legislature has allocated another $250,000 to the HFSRP for the 2018 fiscal year. Thus, evaluation results will be important to inform future healthy corner store policies and initiatives. PMID- 28991157 TI - Geranylgeranylacetone Ameliorates Intestinal Radiation Toxicity by Preventing Endothelial Cell Dysfunction. AB - Radiation-induced intestinal toxicity is common among cancer patients after radiotherapy. Endothelial cell dysfunction is believed to be a critical contributor to radiation tissue injury in the intestine. Geranylgeranylacetone (GGA) has been used to treat peptic ulcers and gastritis. However, the protective capacity of GGA against radiation-induced intestinal injury has not been addressed. Therefore, we investigated whether GGA affects intestinal damage in mice and vascular endothelial cell damage in vitro. GGA treatment significantly ameliorated intestinal injury, as evident by intestinal crypt survival, villi length and the subsequently prolonged survival time of irradiated mice. In addition, intestinal microvessels were also significantly preserved in GGA treated mice. To clarify the effect of GGA on endothelial cell survival, we examined endothelial function by evaluating cell proliferation, tube formation, wound healing, invasion and migration in the presence or absence of GGA after irradiation. Our findings showed that GGA plays a role in maintaining vascular cell function; however, it does not protect against radiation-induced vascular cell death. GGA promoted endothelial function during radiation injury by preventing the loss of VEGF/VEGFR1/eNOS signaling and by down-regulating TNFalpha expression in endothelial cells. This finding indicates the potential impact of GGA as a therapeutic agent in mitigating radiation-induced intestinal damage. PMID- 28991158 TI - A Method for Enhancing the Sensing Distance of a Fingerprint Sensor. AB - In this paper, we describe a method for improving the quality of fingerprint images at long sensing distances by reducing the fringe capacitance formed between a pixel and surrounding fingerprint patterns. Air-walls were applied to the glass attached to a fingerprint sensor for reducing the edge capacitance. Fingerprints and air-wall structures were modeled using a three-dimensional capacitance analysis tool. A prototype was fabricated by stacking glass layers with air-walls with a depth of 50 MUm and a pitch of 50 MUm on a silicon-type capacitive sensor. Using the results of simulations and prototype experiments, we confirmed that the proposed air-wall structure achieved high enough resolution to distinguish 2.5-lp/mm fingerprint patterns at a sensing distance of 300 MUm or longer, and its contrast improved from 0.59 to 0.98. PMID- 28991159 TI - Rosmarinic Acid, a Rosemary Extract Polyphenol, Increases Skeletal Muscle Cell Glucose Uptake and Activates AMPK. AB - Skeletal muscle is a major insulin-target tissue and plays an important role in glucose homeostasis. Impaired insulin action in muscles leads to insulin resistance and type 2 diabetes mellitus. 5' AMP-activated kinase (AMPK) is an energy sensor, its activation increases glucose uptake in skeletal muscle and AMPK activators have been viewed as a targeted approach in combating insulin resistance. We previously reported AMPK activation and increased muscle glucose uptake by rosemary extract (RE). In the present study, we examined the effects and the mechanism of action of rosmarinic acid (RA), a major RE constituent, in L6 rat muscle cells. RA (5.0 uM) increased glucose uptake (186 +/- 4.17% of control, p < 0.001) to levels comparable to maximum insulin (204 +/- 10.73% of control, p < 0.001) and metformin (202 +/- 14.37% of control, p < 0.001). Akt phosphorylation was not affected by RA, while AMPK phosphorylation was increased. The RA-stimulated glucose uptake was inhibited by the AMPK inhibitor compound C and was not affected by wortmannin, an inhibitor of phosphoinositide 3-kinase (PI3K). The current study shows an effect of RA to increase muscle glucose uptake and AMPK phosphorylation. RA deserves further study as it shows potential to be used as an agent to regulate glucose homeostasis. PMID- 28991160 TI - Cancer and the LGBTQ Population: Quantitative and Qualitative Results from an Oncology Providers' Survey on Knowledge, Attitudes, and Practice Behaviors. AB - BACKGROUND: Despite growing social acceptance, the LGBTQ population continues to face barriers to healthcare including fear of stigmatization by healthcare providers, and providers' lack of knowledge about LGBTQ-specific health issues. This analysis focuses on the assessment of quantitative and qualitative responses from a subset of providers who identified as specialists that treat one or more of the seven cancers that may be disproportionate in LGBTQ patients. METHODS: A 32-item web-based survey was emailed to 388 oncology providers at a single institution. The survey assessed: demographics, knowledge, attitudes, and practice behaviors. RESULTS: Oncology providers specializing in seven cancer types had poor knowledge of LGBTQ-specific health needs, with fewer than half of the surveyed providers (49.5%) correctly answering knowledge questions. Most providers had overall positive attitudes toward LGBTQ patients, with 91.7% agreeing they would be comfortable treating this population, and would support education and/or training on LGBTQ-related cancer health issues. CONCLUSION: Results suggest that despite generally positive attitudes toward the LGBTQ population, oncology providers who treat cancer types most prevalent among the population, lack knowledge of their unique health issues. Knowledge and practice behaviors may improve with enhanced education and training on this population's specific needs. PMID- 28991161 TI - Novel Semi-Parametric Algorithm for Interference-Immune Tunable Absorption Spectroscopy Gas Sensing. AB - One of the most common limits to gas sensor performance is the presence of unwanted interference fringes arising, for example, from multiple reflections between surfaces in the optical path. Additionally, since the amplitude and the frequency of these interferences depend on the distance and alignment of the optical elements, they are affected by temperature changes and mechanical disturbances, giving rise to a drift of the signal. In this work, we present a novel semi-parametric algorithm that allows the extraction of a signal, like the spectroscopic absorption line of a gas molecule, from a background containing arbitrary disturbances, without having to make any assumption on the functional form of these disturbances. The algorithm is applied first to simulated data and then to oxygen absorption measurements in the presence of strong fringes.To the best of the authors' knowledge, the algorithm enables an unprecedented accuracy particularly if the fringes have a free spectral range and amplitude comparable to those of the signal to be detected. The described method presents the advantage of being based purely on post processing, and to be of extremely straightforward implementation if the functional form of the Fourier transform of the signal is known. Therefore, it has the potential to enable interference immune absorption spectroscopy. Finally, its relevance goes beyond absorption spectroscopy for gas sensing, since it can be applied to any kind of spectroscopic data. PMID- 28991162 TI - Characterizing the Performance of Gas-Permeable Membranes as an Ammonia Recovery Strategy from Anaerobically Digested Dairy Manure. AB - Capturing ammonia from anaerobically digested manure could simultaneously decrease the adverse effects of ammonia inhibition on biogas production, reduce reactive nitrogen (N) loss to the environment, and produce mineral N fertilizer as a by-product. In this study, gas permeable membranes (GPM) were used to capture ammonia from dairy manure and digestate by the diffusion of gaseous ammonia across the membrane where ammonia is captured by diluted acid, forming an aqueous ammonium salt. A lab-scale prototype using tubular expanded polytetrafluoroethylene (ePTFE) GPM was used to (1) characterize the effect of total ammonium nitrogen (TAN) concentration, temperature, and pH on the ammonia capture rate using GPM, and (2) to evaluate the performance of a GPM system in conditions similar to a mesophilic anaerobic digester. The GPM captured ammonia at a rate between 2.2 to 6.3% of gaseous ammonia in the donor solution per day. Capture rate was faster in anaerobic digestate than raw manure. The ammonia capture rate could be predicted using non-linear regression based on the factors of total ammonium nitrogen concentration, temperature, and pH. This use of membranes shows promise in reducing the deleterious impacts of ammonia on both the efficiency of biogas production and the release of reactive N to the environment. PMID- 28991163 TI - Investigation of Oxidation Methods for Waste Soy Sauce Treatment. AB - To obtain a suitable oxidation method for removing the color and lowering the chemical oxygen demand (COD) of waste soy sauce, Fenton (Fe2+), Fenton-like (Fe3+), and ozone (O3) oxidation methods are used as the target reactions. In experimental conditions for Fenton oxidation, the dose of Fe2+ and Fe3+ was varied between 100 mg/L and 300 mg/L. The dose of hydrogen peroxide for the reaction was injected from 100-1000 mg/L. For ozone oxidation, the pH was increased from 3 to 14 and the O3-containing gas was supplied continuously for 30 min through a gas diffuser at the bottom of the reactor at different applied O3 doses (10-90 mg/L). We subjected it to a simple 1:20 dilution with deionized water to identify the comparison result in detail. O3 oxidation shows the highest efficiencies of color removal (81.1%) and COD lowering (64.9%) among the three oxidation methods. This is mainly due to the fact that it has a relatively large amount of hydroxyl radical, resulting in the degradation of organics. Thus, O3 oxidation could be a promising method for removing the color and lowering the COD of waste soy sauce. The critical parameters (pH and applied O3 dose) were varied systematically to optimize O3 oxidation. It was found that the optimum pH and applied O3 dose are 11.0 mg/L and 50.0 mg/L, respectively (color removal = 34.2%, COD removal = 27.4%). PMID- 28991164 TI - Differential Expression Profile of lncRNAs from Primary Human Hepatocytes Following DEET and Fipronil Exposure. AB - While the synthesis and use of new chemical compounds is at an all-time high, the study of their potential impact on human health is quickly falling behind, and new methods are needed to assess their impact. We chose to examine the effects of two common environmental chemicals, the insect repellent N,N-diethyl-m-toluamide (DEET) and the insecticide fluocyanobenpyrazole (fipronil), on transcript levels of long non-protein coding RNAs (lncRNAs) in primary human hepatocytes using a global RNA-Seq approach. While lncRNAs are believed to play a critical role in numerous important biological processes, many still remain uncharacterized, and their functions and modes of action remain largely unclear, especially in relation to environmental chemicals. RNA-Seq showed that 100 uM DEET significantly increased transcript levels for 2 lncRNAs and lowered transcript levels for 18 lncRNAs, while fipronil at 10 uM increased transcript levels for 76 lncRNAs and decreased levels for 193 lncRNAs. A mixture of 100 uM DEET and 10 uM fipronil increased transcript levels for 75 lncRNAs and lowered transcript levels for 258 lncRNAs. This indicates a more-than-additive effect on lncRNA transcript expression when the two chemicals were presented in combination versus each chemical alone. Differentially expressed lncRNA genes were mapped to chromosomes, analyzed by proximity to neighboring protein-coding genes, and functionally characterized via gene ontology and molecular mapping algorithms. While further testing is required to assess the organismal impact of changes in transcript levels, this initial analysis links several of the dysregulated lncRNAs to processes and pathways critical to proper cellular function, such as the innate and adaptive immune response and the p53 signaling pathway. PMID- 28991165 TI - Synthesis of Novel Glycerol-Derived 1,2,3-Triazoles and Evaluation of Their Fungicide, Phytotoxic and Cytotoxic Activities. AB - The synthesis of a series of 1,2,3-triazoles using glycerol as starting material is described. The key step in the preparation of these triazolic derivatives is the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), also known as click reaction, between 4-(azidomethyl)-2,2-dimethyl-1,3-dioxolane (3) and different terminal alkynes. The eight prepared derivatives were evaluated with regard to their fungicide, phytotoxic and cytotoxic activities. The fungicidal activity was assessed in vitro against Colletotrichum gloeosporioides, the causative agent of papaya anthracnose. It was found that the compounds 1-(1-((2,2-dimethyl-1,3 dioxolan-4-yl)methyl)-1H-1,2,3-triazol-4-yl)-cyclo-hexanol (4g) and 2-(1-((2,2 dimethyl-1,3-dioxolan-4-yl)methyl)-1H-1,2,3-triazol-4-yl)propan-2-ol (4h) demonstrated high efficiency in controlling C. gloeosporioides when compared to the commercial fungicide tebuconazole. The triazoles did not present any phytotoxic effect when evaluated against Lactuca sativa. However, five derivatives were mitodepressive, inducing cell death detected by the presence of condensed nuclei and acted as aneugenic agents in the cell cycle of L. sativa. It is believed that glycerol derivatives bearing 1,2,3-triazole functionalities may represent a promising scaffold to be explored for the development of new agents to control C. gloeosporioides. PMID- 28991166 TI - Impact of Living Alone on Depressive Symptoms in Older Korean Widows. AB - We examined the relationship between living alone and the prevalence of depressive symptoms in older Korean widows and assessed the individual contributions of health, social ties, and socioeconomic factors to the development of depressive symptoms. The study was a secondary analysis using data from widows, 65 years of age and older, who participated in the Living Profiles of Older People Survey (LPOPS). A logistic regression analysis was used to evaluate the contributions of health, social ties, and socioeconomic factors to the development of depressive symptoms. Working status and equivalent household income were significantly associated with depressive symptoms in both those living with others and those living alone. Adjustment for health status and social ties did not change the impact of living alone on the prevalence of depressive symptoms. However, adjustment for equivalent household income eliminated the negative association between living alone and depressive symptoms. Our findings indicate that economic resources are more important than health and social ties for alleviating the negative impact of living alone on the development of depressive symptoms in older widows. PMID- 28991168 TI - Profitability Analysis of Soybean Oil Processes. AB - Soybean oil production is the basic process for soybean applications. Cash flow analysis is used to estimate the profitability of a manufacturing venture. Besides capital investments, operating costs, and revenues, the interest rate is the factor to estimate the net present value (NPV), break-even points, and payback time; which are benchmarks for profitability evaluation. The positive NPV and reasonable payback time represent a profitable process, and provide an acceptable projection for real operating. Additionally, the capacity of the process is another critical factor. The extruding-expelling process and hexane extraction are the two typical approaches used in industry. When the capacities of annual oil production are larger than 12 and 173 million kg respectively, these two processes are profitable. The solvent free approach, known as enzyme assisted aqueous extraction process (EAEP), is profitable when the capacity is larger than 17 million kg of annual oil production. PMID- 28991167 TI - Achiral Mannich-Base Curcumin Analogs Induce Unfolded Protein Response and Mitochondrial Membrane Depolarization in PANC-1 Cells. AB - Achiral Mannich-type curcumin analogs have been synthetized and assayed for their cytotoxic activity. The anti-proliferative and cytotoxic activity of curcuminoids has been tested on human non-small-cell lung carcinoma (A549), hepatocellular carcinoma (HepG2) and pancreatic cancer cell line (PANC-1). Based on the highest anti-proliferative activity nine drug candidates were further tested and proved to cause phosphatidylserine exposure as an early sign of apoptosis. Curcumin analogs with the highest apoptotic activity were selected for mechanistic studies in the most sensitive PANC-1 cells. Cytotoxic activity was accompanied by cytostatic effect since curcumin and analogs treatment led to G0/G1 cell cycle arrest. Moreover, cytotoxic effect could be also detected via the accumulation of curcuminoids in the endoplasmic reticulum (ER) and the up-regulation of ER stress related unfolded protein response (UPR) genes: HSPA5, ATF4, XBP1, and DDIT3. The activated UPR induced mitochondrial membrane depolarization, caspase-3 activation and subsequent DNA breakdown in PANC-1 cells. Achiral curcumin analogs, C509, C521 and C524 possessed superior, 40-times more potent cytotoxic activity compared to natural dihydroxy-dimetoxycurcumin in PANC-1 cells. PMID- 28991169 TI - Analysis of Transmission and Control of Tuberculosis in Mainland China, 2005 2016, Based on the Age-Structure Mathematical Model. AB - Tuberculosis (TB), an air-borne infectious disease, is a major public-health problem in China. The reported number of the active tuberculosis cases is about one million each year. The morbidity data for 2005-2012 reflect that the difference in morbidity based on age group is significant, thus the role of age structure on the transmission of TB needs to be further developed. In this work, based on the reported data and the observed morbidity characteristics, we propose a susceptible-exposed-infectious-recovered (SEIR) epidemic model with age groupings, involving three categories: children, the middle-aged, and senior to investigate the role of age on the transmission of tuberculosis in Mainland China from 2005 to 2016. Then, we evaluated the parameters by the Least Square method and simulated the model and it had good alignment with the reported infected TB data in Mainland China. Furthermore, we estimated the basic reproduction number R0 of 1.7858, with an obtained 95% confidence interval for R0 of (1.7752, 1.7963) by Latin hypercube sampling, and we completed a sensitivity analysis of R0 in terms of some parameters. Our study demonstrates that diverse age groups have different effects on TB. Two effective measures were found that would help reach the goals of theWorld Health Organization (WHO) End TB Strategy: an increase in the recovery rate and the reduction in the infectious rate of the senior age group. PMID- 28991170 TI - Diagnostic Accuracy of FebriDx: A Rapid Test to Detect Immune Responses to Viral and Bacterial Upper Respiratory Infections. AB - C-reactive protein (CRP) and myxovirus resistance protein A (MxA) are associated with bacterial and viral infections, respectively. We conducted a prospective, multicenter, cross-sectional study of adults and children with febrile upper respiratory tract infections (URIs) to evaluate the diagnostic accuracy of a rapid CRP/MxA immunoassay to identify clinically significant bacterial infection with host response and acute pathogenic viral infection. The reference standard for classifying URI etiology was an algorithm that included throat bacterial culture, upper respiratory PCR for viral and atypical pathogens, procalcitonin, white blood cell count, and bandemia. The algorithm also allowed for physician override. Among 205 patients, 25 (12.2%) were classified as bacterial, 53 (25.9%) as viral, and 127 (62.0%) negative by the reference standard. For bacterial detection, agreement between FebriDx and the reference standard was 91.7%, with FebriDx having a sensitivity of 80% (95% CI: 59-93%), specificity of 93% (89 97%), positive predictive value (PPV) of 63% (45-79%), and a negative predictive value (NPV) of 97% (94-99%). For viral detection, agreement was 84%, with a sensitivity of 87% (75-95%), specificity of 83% (76-89%), PPV of 64% (63-75%), and NPV of 95% (90-98%). FebriDx may help to identify clinically significant immune responses associated with bacterial and viral URIs that are more likely to require clinical management or therapeutic intervention, and has potential to assist with antibiotic stewardship. PMID- 28991172 TI - Improving the Accuracy and Training Speed of Motor Imagery Brain-Computer Interfaces Using Wavelet-Based Combined Feature Vectors and Gaussian Mixture Model-Supervectors. AB - In this paper, we propose a set of wavelet-based combined feature vectors and a Gaussian mixture model (GMM)-supervector to enhance training speed and classification accuracy in motor imagery brain-computer interfaces. The proposed method is configured as follows: first, wavelet transforms are applied to extract the feature vectors for identification of motor imagery electroencephalography (EEG) and principal component analyses are used to reduce the dimensionality of the feature vectors and linearly combine them. Subsequently, the GMM universal background model is trained by the expectation-maximization (EM) algorithm to purify the training data and reduce its size. Finally, a purified and reduced GMM supervector is used to train the support vector machine classifier. The performance of the proposed method was evaluated for three different motor imagery datasets in terms of accuracy, kappa, mutual information, and computation time, and compared with the state-of-the-art algorithms. The results from the study indicate that the proposed method achieves high accuracy with a small amount of training data compared with the state-of-the-art algorithms in motor imagery EEG classification. PMID- 28991171 TI - Approaches and Perspectives for Development of African Swine Fever Virus Vaccines. AB - African swine fever (ASF) is a complex disease of swine, caused by a large DNA virus belonging to the family Asfarviridae. The disease shows variable clinical signs, with high case fatality rates, up to 100%, in the acute forms. ASF is currently present in Africa and Europe where it circulates in different scenarios causing a high socio-economic impact. In most affected regions, control has not been effective in part due to lack of a vaccine. The availability of an effective and safe ASFV vaccines would support and enforce control-eradication strategies. Therefore, work leading to the rational development of protective ASF vaccines is a high priority. Several factors have hindered vaccine development, including the complexity of the ASF virus particle and the large number of proteins encoded by its genome. Many of these virus proteins inhibit the host's immune system thus facilitating virus replication and persistence. We review previous work aimed at understanding ASFV-host interactions, including mechanisms of protective immunity, and approaches for vaccine development. These include live attenuated vaccines, and "subunit" vaccines, based on DNA, proteins, or virus vectors. In the shorter to medium term, live attenuated vaccines are the most promising and best positioned candidates. Gaps and future research directions are evaluated. PMID- 28991173 TI - A Gas Chromatographic System for the Detection of Ethylene Gas Using Ambient Air as a Carrier Gas. AB - Ethylene gas is a naturally occurring gas that has an influence on the shelf life of fruit during their transportation in cargo ships. An unintentional exposure of ethylene gas during transportation results in a loss of fruit. A gas chromatographic system is presented here for the detection of ethylene gas. The gas chromatographic system was assembled using a preconcentrator, a printed 3D printed gas chromatographic column, a humidity sensor, solenoid valves, and an electrochemical ethylene gas sensor. Ambient air was used as a carrier gas in the gas chromatographic system. The flow rate was fixed to 10 sccm. It was generated through a mini-pump connected in series with a mass flow controller. The metal oxide gas sensor is discussed with its limitation in ambient air. The results show the chromatogram obtained from metal oxide gas sensor has low stability, drifts, and has uncertain peaks, while the chromatogram from the electrochemical sensor is stable and precise. Furthermore, ethylene gas measurements at higher ppb concentration and at lower ppb concentration were demonstrated with the electrochemical ethylene gas sensor. The system separates ethylene gas and humidity. The chromatograms obtained from the system are stable, and the results are 1.2% repeatable in five similar measurements. The statistical calculation of the gas chromatographic system shows that a concentration of 2.3 ppb of ethylene gas can be detected through this system. PMID- 28991174 TI - Aquaporin-3 in Cancer. AB - Increasing evidence suggests that the water/glycerol channel aquaporin-3 (AQP3) plays a pivotal role in cancer metastasis. AQP3 knockout mice were resistant to skin tumor formation and overexpression correlated with metastasis and poor prognosis in patients with breast or gastric cancer. In cultured cancer cells, increased AQP3 expression stimulated several intracellular signaling pathways and resulted in increased cell proliferation, migration, and invasion as well as aggravation of epithelial-to-mesenchymal transition. Besides AQP facilitated water transport at the leading edge of migrating cells, AQP3 signaling mechanisms are beginning to be unraveled. Here, we give a thorough review of current knowledge regarding AQP3 expression in cancer and how AQP3 contributes to cancer progression via signaling that modulates cellular mechanisms. This review article will expand our understanding of the known pathophysiological findings regarding AQP3 in cancer. PMID- 28991175 TI - Gyroscope Technology and Applications: A Review in the Industrial Perspective. AB - This paper is an overview of current gyroscopes and their roles based on their applications. The considered gyroscopes include mechanical gyroscopes and optical gyroscopes at macro- and micro-scale. Particularly, gyroscope technologies commercially available, such as Mechanical Gyroscopes, silicon MEMS Gyroscopes, Ring Laser Gyroscopes (RLGs) and Fiber-Optic Gyroscopes (FOGs), are discussed. The main features of these gyroscopes and their technologies are linked to their performance. PMID- 28991176 TI - Innate Immune Evasion Mediated by Flaviviridae Non-Structural Proteins. AB - Flaviviridae-caused diseases are a critical, emerging public health problem worldwide. Flaviviridae infections usually cause severe, acute or chronic diseases, such as liver damage and liver cancer resulting from a hepatitis C virus (HCV) infection and high fever and shock caused by yellow fever. Many researchers worldwide are investigating the mechanisms by which Flaviviridae cause severe diseases. Flaviviridae can interfere with the host's innate immunity to achieve their purpose of proliferation. For instance, dengue virus (DENV) NS2A, NS2B3, NS4A, NS4B and NS5; HCV NS2, NS3, NS3/4A, NS4B and NS5A; and West Nile virus (WNV) NS1 and NS4B proteins are involved in immune evasion. This review discusses the interplay between viral non-structural Flaviviridae proteins and relevant host proteins, which leads to the suppression of the host's innate antiviral immunity. PMID- 28991177 TI - Antioxidants Potential of the Filamentous Fungi (Mucor circinelloides). AB - Three important strains of Mucorcircinelloides grown in complete and minimal media for specified period (72 h, 120 h and 168 h) under submerged fermentation conditions were investigated for their potential antioxidants/secondary metabolite production. All mycelial extracts demonstrated effective antioxidant activities in terms of beta-carotene/linoleic acid bleaching, radical scavenging, reduction of metal ions and chelating abilities against ferrous ions. Different extraction methods and solvent systems affected the recovery yield and antioxidant activities of the extracts significantly (p <= 0.05). Ethanolic extracts were found to be rich source of antioxidant components and subsequently more effective in antioxidant properties. Fermentation period and media used also significantly affected (p <= 0.05) the antioxidant production and the resulting antioxidant properties. The (ethanolic) extracts of all the strains from late exponential growth phase (120 h) showed highest antioxidant production with topmost reducing, chelating and radical scavenging capabilities. Strain MC277.49 was found to be the highest producer of antioxidants followed by MC108.16 and WJ11. Phenolic compounds were detected significantly in higher (p <= 0.05) amount succeeded by the condensed tannins and flavonoids. Total phenol content of each extract was attributed to overall antioxidant capacity. Submerged fermentation with nutritional stress conditions were found to be excellent way of producing surplus amount of natural antioxidants/secondary metabolites with their vast potential commercial application in food and pharmaceutical industries. PMID- 28991178 TI - Polyprotein Processing as a Determinant for in Vitro Activity of Semliki Forest Virus Replicase. AB - Semliki Forest virus (SFV) is an arthropod-borne alphavirus that induces membrane invaginations (spherules) in host cells. These harbor the viral replication complexes (RC) that synthesize viral RNA. Alphaviruses have four replicase or nonstructural proteins (nsPs), nsP1-4, expressed as polyprotein P1234. An early RC, which synthesizes minus-strand RNA, is formed by the polyprotein P123 and the polymerase nsP4. Further proteolytic cleavage results in a late RC consisting of nsP1-4 and synthesizing plus strands. Here, we show that only the late RCs are highly active in RNA synthesis in vitro. Furthermore, we demonstrate that active RCs can be isolated from both virus-infected cells and cells transfected with the wild-type replicase in combination with a plasmid expressing a template RNA. When an uncleavable polyprotein P123 and polymerase nsP4 were expressed together with a template, high levels of minus-strand RNA were produced in cells, but RCs isolated from these cells were hardly active in vitro. Furthermore, we observed that the uncleavable polyprotein P123 and polymerase nsP4, which have previously been shown to form spherules even in the absence of the template, did not replicate an exogenous template. Consequently, we hypothesize that the replicase proteins were sequestered in spherules and were no longer able to recruit a template. PMID- 28991179 TI - High-Accuracy Decoupling Estimation of the Systematic Coordinate Errors of an INS and Intensified High Dynamic Star Tracker Based on the Constrained Least Squares Method. AB - Navigation accuracy is one of the key performance indicators of an inertial navigation system (INS). Requirements for an accuracy assessment of an INS in a real work environment are exceedingly urgent because of enormous differences between real work and laboratory test environments. An attitude accuracy assessment of an INS based on the intensified high dynamic star tracker (IHDST) is particularly suitable for a real complex dynamic environment. However, the coupled systematic coordinate errors of an INS and the IHDST severely decrease the attitude assessment accuracy of an INS. Given that, a high-accuracy decoupling estimation method of the above systematic coordinate errors based on the constrained least squares (CLS) method is proposed in this paper. The reference frame of the IHDST is firstly converted to be consistent with that of the INS because their reference frames are completely different. Thereafter, the decoupling estimation model of the systematic coordinate errors is established and the CLS-based optimization method is utilized to estimate errors accurately. After compensating for error, the attitude accuracy of an INS can be assessed based on IHDST accurately. Both simulated experiments and real flight experiments of aircraft are conducted, and the experimental results demonstrate that the proposed method is effective and shows excellent performance for the attitude accuracy assessment of an INS in a real work environment. PMID- 28991180 TI - Robust Regression Analysis of GCMS Data Reveals Differential Rewiring of Metabolic Networks in Hepatitis B and C Patients. AB - About one in 15 of the world's population is chronically infected with either hepatitis virus B (HBV) or C (HCV), with enormous public health consequences. The metabolic alterations caused by these infections have never been directly compared and contrasted. We investigated groups of HBV-positive, HCV-positive, and uninfected healthy controls using gas chromatography-mass spectrometry analyses of their plasma and urine. A robust regression analysis of the metabolite data was conducted to reveal correlations between metabolite pairs. Ten metabolite correlations appeared for HBV plasma and urine, with 18 for HCV plasma and urine, none of which were present in the controls. Metabolic perturbation networks were constructed, which permitted a differential view of the HBV- and HCV-infected liver. HBV hepatitis was consistent with enhanced glucose uptake, glycolysis, and pentose phosphate pathway metabolism, the latter using xylitol and producing threonic acid, which may also be imported by glucose transporters. HCV hepatitis was consistent with impaired glucose uptake, glycolysis, and pentose phosphate pathway metabolism, with the tricarboxylic acid pathway fueled by branched-chain amino acids feeding gluconeogenesis and the hepatocellular loss of glucose, which most probably contributed to hyperglycemia. It is concluded that robust regression analyses can uncover metabolic rewiring in disease states. PMID- 28991181 TI - Association between Milk Consumption and Metabolic Syndrome among Korean Adults: Results from the Health Examinees Study. AB - It has been suggested that a greater dairy consumption, particularly of milk, may have contributed in lowering the prevalence of metabolic syndrome (MetS). A cross sectional analysis was conducted to examine the association between milk consumption and MetS, and its components among Korean adults aged 40-69. A total of 130,420 subjects (43,682 men and 86,738 women) from the Health Examinees Study were selected for the final analysis. Milk consumption was estimated using a validated 106-item food frequency questionnaire. MetS was defined using the National Cholesterol Education Program, Adult Treatment Panel III (NCEP III). Logistic regression analyses were performed to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) between milk consumption and MetS after adjusting for potential confounders. In this study, the average milk consumption was 77.9 g/day, with the overall prevalence of MetS being 26.1% (29.1% in men and 24.6% in women). We found that the prevalence of the MetS was significantly lower in subjects with higher milk consumption (p < 0.0001). Adjusted OR for MetS was significantly lower in the highest milk consumption category (>=1 serving/day among men; >=2 serving/day among women) than those in the lowest milk consumption category (OR: 0.92 95%CI: 0.86-0.99, p trend = 0.0160 in men; OR: 0.68, 95%CI: 0.60-0.76, p trend < 0.0001 in women). Overall, higher milk consumption was inversely associated with the MetS components: elevated waist circumference, elevated triglyceride, and reduced high-density lipoprotein cholesterol (HDL-C) (all p trend < 0.05). This study concludes that higher milk consumption is associated with the lower odds of MetS in Korean adults. PMID- 28991182 TI - Near Retirement Age (>=55 Years) Self-Reported Physical Symptoms and Use of Computers/Mobile Phones at Work and at Leisure. AB - The aim of this research is to study the symptoms and use of computers/mobile phones of individuals nearing retirement age (>=55 years). A questionnaire was sent to 15,000 Finns (aged 18-65). People who were >=55 years of age were compared to the rest of the population. Six thousand one hundred and twenty-one persons responded to the questionnaire; 1226 of them were >=55 years of age. Twenty-four percent of the >=55-year-old respondents used desktop computers daily for leisure; 47.8% of them frequently experienced symptoms in the neck, and 38.5% in the shoulders. Workers aged >=55 years had many more physical symptoms than younger people, except with respect to symptoms of the neck. Female daily occupational users of desktop computers had more physical symptoms in the neck. It is essential to take into account that, for people aged >=55 years, the use of technology can be a sign of wellness. However, physical symptoms in the neck can be associated with the use of computers. PMID- 28991183 TI - Orexin Receptor Multimerization versus Functional Interactions: Neuropharmacological Implications for Opioid and Cannabinoid Signalling and Pharmacogenetics. AB - Orexins/hypocretins are neuropeptides formed by proteolytic cleavage of a precursor peptide, which are produced by neurons found in the lateral hypothalamus. The G protein-coupled receptors (GPCRs) for these ligands, the OX1 and OX2 orexin receptors, are more widely expressed throughout the central nervous system. The orexin/hypocretin system has been implicated in many pathways, and its dysregulation is under investigation in a number of diseases. Disorders in which orexinergic mechanisms are being investigated include narcolepsy, idiopathic sleep disorders, cluster headache and migraine. Human narcolepsy has been associated with orexin deficiency; however, it has only rarely been attributed to mutations in the gene encoding the precursor peptide. While gene variations within the canine OX2 gene hcrtr2 have been directly linked with narcolepsy, the majority of human orexin receptor variants are weakly associated with diseases (the idiopathic sleep disorders, cluster headache and polydipsia-hyponatremia in schizophrenia) or are of potential pharmacogenetic significance. Evidence for functional interactions and/or heterodimerization between wild-type and variant orexin receptors and opioid and cannabinoid receptors is discussed in the context of its relevance to depression and epilepsy. PMID- 28991184 TI - From Delivery to Adoption of Physical Activity Guidelines: Realist Synthesis. AB - BACKGROUND: Evidence-based guidelines published by health authorities for the promotion of health-enhancing physical activity (PA), continue to be implemented unsuccessfully and demonstrate a gap between evidence and policies. This review synthesizes evidence on factors influencing delivery, adoption and implementation of PA promotion guidelines within different policy sectors (e.g., health, transport, urban planning, sport, education). METHODS: Published literature was initially searched using PubMed, EBSCO, Google Scholar and continued through an iterative snowball technique. The literature review spanned the period 2002-2017. The realist synthesis approach was adopted to review the content of 39 included studies. An initial programme theory with a four-step chain from evidence emersion to implementation of guidelines was tested. RESULTS: The synthesis furthers our understanding of the link between PA guidelines delivery and the actions of professionals responsible for implementation within health services, school departments and municipalities. The main mechanisms identified for guidance implementation were scientific legitimation, enforcement, feasibility, familiarity with concepts and PA habits. Threats emerged to the successful implementation of PA guidelines at national/local jurisdictional levels. CONCLUSIONS: The way PA guidelines are developed may influence their adoption by policy-makers and professionals. Useful lessons emerged that may inform synergies between policymaking and professional practices, promoting win-win multisectoral strategies. PMID- 28991185 TI - Comparison of Health Risk Assessments of Heavy Metals and As in Sewage Sludge from Wastewater Treatment Plants (WWTPs) for Adults and Children in the Urban District of Taiyuan, China. AB - Abstract: To compare the human health risk of heavy metals and As in sewage sludge between adults and children, samples were collected from five wastewater treatment plants (WWTPs) located in the urban district of Taiyuan, the capital of Shanxi. Heavy metals and As in sewage sludge can be ranked according to the mean concentration in the following order: Cu > Cr > Zn > Pb > As > Hg > Cd. Compared with the concentration limit set by different countries, the heavy metals contents in sewage sludge were all within the standard limits, except for the content of As, which was higher than the threshold limit established by Canada. A health risk assessment recommended by the United States Environmental Protection Agency (USEPA) was used to compare the non-cancer risk and cancer risk between adults and children. Based on the mean and 95% upper confidence limit (UCL) of the average daily dose (ADD), heavy metals and As can be ranked in the order of Cu > Cr > Zn > Pb > As > Hg > Cd for adults, and Cu > Cr > Zn > Pb > Hg > As > Cd for children. Moreover, results of ADDingest and ADDinhale indicated that ingestion was the main pathway for heavy metals and As exposure for both adults and children, and the sum of ADD implied that the exposure to all heavy metals and As for children was 8.65 and 9.93 times higher, respectively, than that for adults according to the mean and 95% UCL. For the non-carcinogenic risk, according to the hazard quotient (HQ), the risk of Cu, Hg and Cr was higher than the risk of Zn and Pb. The hazard index (HI) for adults was 0.144 and 0.208 for the mean and 95% UCL, which was less than the limit value of 1; for children, the HI was 1.26 and 2.25, which is higher than the limit value of 1. This result indicated that children had non-carcinogenic risk, but adults did not. Furthermore, ingestion was the main pathway for non-carcinogenic risk exposure by the HQingest and HQinhale. For the carcinogenic risk, Cd and As were classified as carcinogenic pollutants. The values of RISK for the mean and 95% UCL for adults and children all exceeded the limit value of 1 * 10-5, which implied that adults and children had a carcinogenic risk, and this risk was higher for children than for adults. The results of RISK for As and Cd implied that As was the main pollutant for carcinogenic risk. Moreover, the results of RISKingest and RISKinhale indicated that ingestion was the main pathway. Uncertainty analysis was performed, and the risk ranges of it were greater than certainty analysis, which implied that uncertainty analysis was more conservative than certainty analysis. A comparison of the non-carcinogenic risk and carcinogenic risk for adults and children indicated that children were more sensitive and vulnerable than adults when exposed to the same pollutant in the environment. PMID- 28991186 TI - Relationships among Environment, Climate, and Longevity in China. AB - Human longevity is influenced by environment and nutrition. We considered environmental and nutritional factors relating to longevity in Chinese cities. We found higher 85+/65+ distribution ratios, indicating enhanced longevity, in the coastal and southern regions of China. These areas also featured higher humidity, low standard deviation of monthly temperature, higher levels of selenium (Se) distribution in soil, and greater sea fish consumption. Moderate climate is more conducive to longevity, however, there is no significant difference in longevity between different sub-climatic types within moderate climate; the relation between humidity and longevity is not always positive, the relation between altitude and longevity is not always negative. Nutritional factors like Se and omega-3 fatty acids contained in sea fish were crucial to longevity. In contrast, the consumption of meat and freshwater fish were less related to longevity. Taken together, humidity, altitude, and per capita sea fish consumption, when evaluated via geographically weighted regression, explained 66% and 68% of longevity among Chinese individuals in 2000 and 2010, respectively. Other factors require further discussion. PMID- 28991187 TI - Peptides from Colochirus robustus Enhance Immune Function via Activating CD3zeta- and ZAP-70-Mediated Signaling in C57BL/6 Mice. AB - Colochirus robustus, a species of sea cucumber, has long been used in East and Southeast Asia as nutritious food as well as for certain medicinal purpose. Studies have shown a number of biological functions associated with consumption of sea cucumber, many of which are attributed to its major component, sea cucumber peptides (SCP). However, how SCP impacts immune system, which is critical for host defense, has not been defined. To address this issue, in the present study, we conducted comprehensive analysis of immune function after oral administration of SCP (0, 25, 50, and 75 mg/kg body weigh) for eight weeks in C57BL/6 mice. We found that SCP treatment significantly enhanced lymphocyte proliferation, serum albumin (ALB) levels, and the natural killer (NK) cell activity. Moreover, SCP promoted functions of helper T cells (Th) as indicated by increased production of Th1 type cytokines of Interleukin (IL)-1beta, IL-2, Interferon (IFN)-gamma and TNF-alpha and Th2 type cytokines (IL-4, IL-6, and IL 10). To determine the effective components, SCP was hydrolyzed into 16 types of constituent amino acids in simulated gastrointestinal digestion and these hydrolytic amino acids (HAA) were used for the mechanistic studies in the in vitro models. Results showed that HAA enhanced lymphocyte proliferation and production of IL-2, IL-10 and IFN-gamma. Furthermore, CD3zeta (CD3zeta) and zeta chain-associated protein kinase 70 (ZAP-70), the signaling molecules essential for activating T lymphocytes, were significantly up-regulated after HAA treatment. In summary, our results suggest that SCP is effective in enhancing immune function by activating T cells via impacting CD3zeta- and ZAP-70-mediated signaling pathway. PMID- 28991188 TI - Supporting the Development and Adoption of Automatic Lameness Detection Systems in Dairy Cattle: Effect of System Cost and Performance on Potential Market Shares. AB - Most automatic lameness detection system prototypes have not yet been commercialized, and are hence not yet adopted in practice. Therefore, the objective of this study was to simulate the effect of detection performance (percentage missed lame cows and percentage false alarms) and system cost on the potential market share of three automatic lameness detection systems relative to visual detection: a system attached to the cow, a walkover system, and a camera system. Simulations were done using a utility model derived from survey responses obtained from dairy farmers in Flanders, Belgium. Overall, systems attached to the cow had the largest market potential, but were still not competitive with visual detection. Increasing the detection performance or lowering the system cost led to higher market shares for automatic systems at the expense of visual detection. The willingness to pay for extra performance was ?2.57 per % less missed lame cows, ?1.65 per % less false alerts, and ?12.7 for lame leg indication, respectively. The presented results could be exploited by system designers to determine the effect of adjustments to the technology on a system's potential adoption rate. PMID- 28991189 TI - Translational Implication of Galectin-9 in the Pathogenesis and Treatment of Viral Infection. AB - The interaction between galectin-9 and its receptor, Tim-3, triggers a series of signaling events that regulate immune responses. The expression of galectin-9 has been shown to be increased in a variety of target cells of many different viruses, such as hepatitis C virus (HCV), hepatitis B virus (HBV), herpes simplex virus (HSV), influenza virus, dengue virus (DENV), and human immunodeficiency virus (HIV). This enhanced expression of galectin-9 following viral infection promotes significant changes in the behaviors of the virus-infected cells, and the resulting events tightly correlate with the immunopathogenesis of the viral disease. Because the human immune response to different viral infections can vary, and the lack of appropriate treatment can have potentially fatal consequences, understanding the implications of galectin-9 is crucial for developing better methods for monitoring and treating viral infections. This review seeks to address how we can apply the current understanding of galectin-9 function to better understand the pathogenesis of viral infection and better treat viral diseases. PMID- 28991191 TI - Cooperative Localization for Multi-AUVs Based on GM-PHD Filters and Information Entropy Theory. AB - Cooperative localization (CL) is considered a promising method for underwater localization with respect to multiple autonomous underwater vehicles (multi AUVs). In this paper, we proposed a CL algorithm based on information entropy theory and the probability hypothesis density (PHD) filter, aiming to enhance the global localization accuracy of the follower. In the proposed framework, the follower carries lower cost navigation systems, whereas the leaders carry better ones. Meanwhile, the leaders acquire the followers' observations, including both measurements and clutter. Then, the PHD filters are utilized on the leaders and the results are communicated to the followers. The followers then perform weighted summation based on all received messages and obtain a final positioning result. Based on the information entropy theory and the PHD filter, the follower is able to acquire a precise knowledge of its position. PMID- 28991190 TI - Evolution Analysis of the Aux/IAA Gene Family in Plants Shows Dual Origins and Variable Nuclear Localization Signals. AB - The plant hormone auxin plays pivotal roles in many aspects of plant growth and development. The auxin/indole-3-acetic acid (Aux/IAA) gene family encodes short lived nuclear proteins acting on auxin perception and signaling, but the evolutionary history of this gene family remains to be elucidated. In this study, the Aux/IAA gene family in 17 plant species covering all major lineages of plants is identified and analyzed by using multiple bioinformatics methods. A total of 434 Aux/IAA genes was found among these plant species, and the gene copy number ranges from three (Physcomitrella patens) to 63 (Glycine max). The phylogenetic analysis shows that the canonical Aux/IAA proteins can be generally divided into five major clades, and the origin of Aux/IAA proteins could be traced back to the common ancestor of land plants and green algae. Many truncated Aux/IAA proteins were found, and some of these truncated Aux/IAA proteins may be generated from the C-terminal truncation of auxin response factor (ARF) proteins. Our results indicate that tandem and segmental duplications play dominant roles for the expansion of the Aux/IAA gene family mainly under purifying selection. The putative nuclear localization signals (NLSs) in Aux/IAA proteins are conservative, and two kinds of new primordial bipartite NLSs in P. patens and Selaginella moellendorffii were discovered. Our findings not only give insights into the origin and expansion of the Aux/IAA gene family, but also provide a basis for understanding their functions during the course of evolution. PMID- 28991192 TI - In-Season Yield Prediction of Cabbage with a Hand-Held Active Canopy Sensor. AB - Efficient and precise yield prediction is critical to optimize cabbage yields and guide fertilizer application. A two-year field experiment was conducted to establish a yield prediction model for cabbage by using the Greenseeker hand-held optical sensor. Two cabbage cultivars (Jianbao and Pingbao) were used and Jianbao cultivar was grown for 2 consecutive seasons but Pingbao was only grown in the second season. Four chemical nitrogen application rates were implemented: 0, 80, 140, and 200 kg.N.ha-1. Normalized difference vegetation index (NDVI) was collected 20, 50, 70, 80, 90, 100, 110, 120, 130, and 140 days after transplanting (DAT). Pearson correlation analysis and regression analysis were performed to identify the relationship between the NDVI measurements and harvested yields of cabbage. NDVI measurements obtained at 110 DAT were significantly correlated to yield and explained 87-89% and 75-82% of the cabbage yield variation of Jianbao cultivar over the two-year experiment and 77-81% of the yield variability of Pingbao cultivar. Adjusting the yield prediction models with CGDD (cumulative growing degree days) could make remarkable improvement to the accuracy of the prediction model and increase the determination coefficient to 0.82, while the modification with DFP (days from transplanting when GDD > 0) values did not. The integrated exponential yield prediction equation was better than linear or quadratic functions and could accurately make in-season estimation of cabbage yields with different cultivars between years. PMID- 28991193 TI - Sphingosine Kinase 1 and Sphingosine-1-Phosphate Signaling in Colorectal Cancer. AB - Sphingosine kinase 1 (Sphk1) is a highly conserved lipid kinase that phosphorylates sphingosine to form sphingosine-1-phosphate (S1P). Growing studies have demonstrated that Sphk1 is overexpressed in various types of solid cancers and can be induced by growth factors, cytokines, and carcinogens, leading to the increase of S1P production. Subsequently, the increased Sphk1/S1P facilitates cancer cell proliferation, mobility, angiogenesis, invasion, and metastasis. Therefore, Sphk1/S1P signaling plays oncogenic roles. This review summarizes the features of Sphk1/S1P signaling and their functions in colorectal cancer cell growth, tumorigenesis, and metastasis, as well as the possible underlying mechanisms. PMID- 28991195 TI - A Microwave Thermostatic Reactor for Processing Liquid Materials Based on a Heat Exchanger. AB - Microwaves have been widely used in the treatment of different materials. However, the existing adjustable power thermostatic reactors cannot be used to analyze materials characteristics under microwave effects. In this paper, a microwave thermostatic chemical reactor for processing liquid materials is proposed, by controlling the velocity of coolant based on PLC (programmable logic controller) in different liquid under different constant electric field intensity. A nonpolar coolant (Polydimethylsiloxane), which is completely microwave transparent, is employed to cool the liquid materials. Experiments are performed to measure the liquid temperature using optical fibers, the results show that the precision of temperature control is at the range of +/-0.5 degrees C. Compared with the adjustable power thermostatic control system, the effect of electric field changes on material properties are avoided and it also can be used to detect the properties of liquid materials and special microwave effects. PMID- 28991194 TI - PARP1 in Carcinomas and PARP1 Inhibitors as Antineoplastic Drugs. AB - Poly (ADP-ribose) polymerase 1 (PARP1), the best-studied isoform of the nuclear enzyme PARP family, plays a pivotal role in cellular biological processes, such as DNA repair, gene transcription, and so on. PARP1 has been found to be overexpressed in various carcinomas. These all indicate the clinical potential of PARP1 as a therapeutic target of human malignancies. Additionally, multiple preclinical research studies and clinical trials demonstrate that inhibition of PARP1 can repress tumor growth and metastasis. Up until now, PARP1 inhibitors are clinically used not only for monotherapy to suppress various tumors, but also for adjuvant therapy, to maintain or enhance therapeutic effects of mature antineoplastic drugs, as well as protect patients from chemotherapy and surgery induced injury. To supply a framework for understanding recent research progress of PARP1 in carcinomas, we review the structure, expression, functions, and mechanisms of PARP1, and summarize the clinically mature PARP1-related anticancer agents, to provide some ideas for the development of other promising PARP1 inhibitors in antineoplastic therapy. PMID- 28991196 TI - Phaseolus acutifolius Lectin Fractions Exhibit Apoptotic Effects on Colon Cancer: Preclinical Studies Using Dimethilhydrazine or Azoxi-Methane as Cancer Induction Agents. AB - Phaseolus acutifolius (Tepary bean) lectins have been studied as cytotoxic molecules on colon cancer cells. The toxicological profile of a Tepary bean lectin fraction (TBLF) has shown low toxicity in experimental animals; exhibiting anti-nutritional effects such as a reduction in body weight gain and a decrease in food intake when using a dose of 50 mg/kg on alternate days for six weeks. Taking this information into account, the focus of this work was to evaluate the effect of the TBLF on colon cancer using 1,2-dimethylhydrazine (DMH) or azoxy methane/dextran sodium sulfate (AOM/DSS) as colon cancer inductors. Rats were treated with DMH or AOM/DSS and then administered with TBFL (50 mg/kg) for six weeks. TBLF significantly decreased early tumorigenesis triggered by DMH by 70%, but without any evidence of an apoptotic effect. In an independent experiment, AOM/DSS was used to generate aberrant cryptic foci, which decreased by 50% after TBLF treatment. TBLF exhibited antiproliferative and proapoptotic effects related to a decrease of the signal transduction pathway protein Akt in its activated form and an increase of caspase 3 activity, but not to p53 activation. Further studies will deepen our knowledge of specific apoptosis pathways and cellular stress processes such as oxidative damage. PMID- 28991197 TI - Differential Proteome Analysis of Extracellular Vesicles from Breast Cancer Cell Lines by Chaperone Affinity Enrichment. AB - The complexity of human tissue fluid precludes timely identification of cancer biomarkers by immunoassay or mass spectrometry. An increasingly attractive strategy is to primarily enrich extracellular vesicles (EVs) released from cancer cells in an accelerated manner compared to normal cells. The Vn96 peptide was herein employed to recover a subset of EVs released into the media from cellular models of breast cancer. Vn96 has affinity for heat shock proteins (HSPs) decorating the surface of EVs. Reflecting their cells of origin, cancer EVs displayed discrete differences from those of normal phenotype. GELFrEE LC/MS identified an extensive proteome from all three sources of EVs, the vast majority having been previously reported in the ExoCarta database. Pathway analysis of the Vn96-affinity proteome unequivocally distinguished EVs from tumorigenic cell lines (SKBR3 and MCF-7) relative to a non-tumorigenic source (MCF-10a), particularly with regard to altered metabolic enzymes, signaling, and chaperone proteins. The protein data sets provide valuable information from material shed by cultured cells. It is probable that a vast amount of biomarker identities may be collected from established and primary cell cultures using the approaches described here. PMID- 28991198 TI - Gypmacrophin A, a Rare Pentacyclic Sesterterpenoid, Together with Three Depsides, Functioned as New Chemical Evidence for Gypsoplaca macrophylla (Zahlbr.) Timdal Identification. AB - The phytochemical investigation on 1 g of materials from Gypsoplacamacrophylla (Zahlbr.) Timdal resulted in the discovery of gypmacrophin A, a rare pentacyclic sesterterpenoid; brialmontin III, a new polysubstituted depside and two known ones, brialmontins I and II. The structure and absolute configurations of gypmacrophin A were elucidated by spectroscopic analyses and computational methods. Gypmacrophin A showed weak inhibition of AchE with an IC50 value of 32.03 MUM. The four compounds provided new chemical evidence for G. macrophylla identification. PMID- 28991199 TI - Modelling the Ozone-Based Treatments for Inactivation of Microorganisms. AB - The paper presents the development of a model for ozone treatment in a dynamic bed of different microorganisms (Bacillus subtilis, B. cereus, B. pumilus, Escherichia coli, Pseudomonas fluorescens, Aspergillus niger, Eupenicillium cinnamopurpureum) on a heterogeneous matrix (juniper berries, cardamom seeds) initially treated with numerous ozone doses during various contact times was studied. Taking into account various microorganism susceptibility to ozone, it was of great importance to develop a sufficiently effective ozone dose to preserve food products using different strains based on the microbial model. For this purpose, we have chosen the Weibull model to describe the survival curves of different microorganisms. Based on the results of microorganism survival modelling after ozone treatment and considering the least susceptible strains to ozone, we selected the critical ones. Among tested strains, those from genus Bacillus were recognized as the most critical strains. In particular, B. subtilis and B. pumilus possessed the highest resistance to ozone treatment because the time needed to achieve the lowest level of its survival was the longest (up to 17.04 min and 16.89 min for B. pumilus reduction on juniper berry and cardamom seed matrix, respectively). Ozone treatment allow inactivate microorganisms to achieving lower survival rates by ozone dose (20.0 g O3/m3 O2, with a flow rate of 0.4 L/min) and contact time (up to 20 min). The results demonstrated that a linear correlation between parameters p and k in Weibull distribution, providing an opportunity to calculate a fitted equation of the process. PMID- 28991200 TI - Joint Power Charging and Routing in Wireless Rechargeable Sensor Networks. AB - The development of wireless power transfer (WPT) technology has inspired the transition from traditional battery-based wireless sensor networks (WSNs) towards wireless rechargeable sensor networks (WRSNs). While extensive efforts have been made to improve charging efficiency, little has been done for routing optimization. In this work, we present a joint optimization model to maximize both charging efficiency and routing structure. By analyzing the structure of the optimization model, we first decompose the problem and propose a heuristic algorithm to find the optimal charging efficiency for the predefined routing tree. Furthermore, by coding the many-to-one communication topology as an individual, we further propose to apply a genetic algorithm (GA) for the joint optimization of both routing and charging. The genetic operations, including tree based recombination and mutation, are proposed to obtain a fast convergence. Our simulation results show that the heuristic algorithm reduces the number of resident locations and the total moving distance. We also show that our proposed algorithm achieves a higher charging efficiency compared with existing algorithms. PMID- 28991201 TI - An Evaluation of the Healthiness of the Indian Packaged Food and Beverage Supply. AB - Availability of less-healthy packaged food and beverage products has been implicated as an important driver of obesity and diet-related disease. An increasing number of packaged foods and beverages are sold in India. Our objective was to evaluate the healthiness of packaged foods sold by India's largest manufacturers. Healthiness was assessed using the Australian Health Star Rating (HSR) system and the World Health Organization's European Regional Office (WHO Euro) Nutrient Profile Model. Sales-value-weighted mean healthiness and the proportions of "healthy" products (using a validated HSR cut-off of >=3.5, and products meeting WHO Euro criteria as healthy enough to market to children) were calculated overall, by company and by food category. Nutrient information for 943 products sold by the 11 largest Indian manufacturers was obtained from nutrient labels, company websites or directly from the manufacturer. Healthiness was low overall (mean HSR 1.8 out of 5.0 stars) with a low proportion defined as "healthy" by both HSR (17%) and also by WHO Euro criteria (8%). There were marked differences in the healthiness of similar products within food categories. Substantial variation between companies (minimum sales-value-weighted mean HSR 0.5 for Company G, versus maximum HSR 3.0 for Company F) was a result of differences in the types of products sold and the nutritional composition of individual products. There are clear opportunities for India's largest food companies to improve both the nutritional quality of individual products and to improve their product mix to include a greater proportion of healthy products. PMID- 28991202 TI - Solid-State Form Characterization of Riparin I. AB - Riparin I is an alkamide with potential anxiolytic activity in preclinical studies. The characterization and understanding of solid-state properties play an importance role in drug development. For this work, the solid state of five riparin I batches (RIP-1, RIP-2, RIP-3, RIP-4, and RIP-5), obtained by the same synthesis process, were characterized by Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC), DSC-photovisual, Thermogravimetry (TG), Fourier Transform Infrared (FTIR), Pyrolysis (Pyr-GC/MS), X-ray Powder Diffraction (PXRD), and Solid-State Nuclear Magnetic Resonance (ssNMR) techniques. Batches of riparin I with different crystal habits resulting in crystallization impurities were observed, which can be attributed to the presence of triethylamine. The main differences were observed by DSC, PXRD, and ssNMR analysis. DSC curves of RIP-2 and RIP-3 presented endothermic peaks at different temperatures of fusion, which can be attributed to the mixture of different crystalline forms. PXRD and ssNMR results confirmed crystallinity differences. The results offer evidence of the importance of controlling the reproducibility of the synthesis in order to obtain the adequate morphology for therapeutic efficacy and avoiding future problems in quality control of riparin I products. PMID- 28991203 TI - Pharmacy Practice and Education in the Czech Republic. AB - The PHARMINE ("Pharmacy Education in Europe") project studied the organisation of pharmacy education, practice and legislation in the European Union (EU) with the objectives of evaluating to what degree harmonisation had taken place with the EU, and producing documents on each individual EU member state. Part of this work was in the form of a survey of pharmacy education, practice, and legislation in the various member states. We will publish the individual member state surveys as reference documents. This paper presents the results of the PHARMINE survey on pharmacy education, training, and practice in the Czech Republic. Czech community pharmacies sell and provide advice on Rx and Over-the-counter (OTC) medicines; they also provide diagnostic services (e.g., blood pressure measurement). Pharmacists (lekarnik in Czech) study for five years and graduate with a Magister (Mgr., equivalent to M.Pharm.) degree. The Mgr. diploma is the only requirement for registration as a pharmacist. Pharmacists can own and manage community pharmacies, or work as responsible pharmacists in pharmacies. All practising pharmacists must be registered with the Czech Chamber of Pharmacists. The ownership of a community pharmacy is not restricted to members of the pharmacy profession; the majority of pharmacies are organised into various pharmacy chains. There are two universities providing higher education in pharmacy in the Czech Republic: the Faculty of Pharmacy in Hradec Kralove, Charles University, which was established in 1969, and the Faculty of Pharmacy of the University of Veterinary and Pharmaceutical Sciences in Brno, which was established in 1991. The pharmacy curriculum is organized as a seamless, fully integrated, five-year master degree course. There is a six-month traineeship supervised by the university, which usually takes place during the fifth year. Thus, the pharmacy curriculum is organised in accordance with the EU directive on sectoral professions that lays down the imperatives for pharmacy education, training, and practice in the various member states of the EU. Currently, no specialisation courses are available at the university level. Specialisation is organised in the form of postgraduate, continuing professional development by the Czech Chamber of Pharmacists, and delivered by the Institute of Postgraduate Education for Health Professions. PMID- 28991204 TI - Influence of Plant Growth Retardants on Quality of Codonopsis Radix. AB - Plant growth retardant (PGR) refers to organics that can inhibit the cell division of plant stem tip sub-apical meristem cells or primordial meristem cell. They are widely used in the cultivation of rhizomatous functional plants; such as Codonopsis Radix, that is a famous Chinese traditional herb. However, it is still unclear whether PGR affects the medicinal quality of C. Radix. In the present study, amino acid analyses, targeted and non-targeted analyses by ultra performance liquid chromatography combined with time-of-flight mass spectrometry (UPLC-TOF-MS) and gas chromatography-MS were used to analyze and compare the composition of untreated C. Radix and C. Radix treated with PGR. The contents of two key bioactive compounds, lobetyolin and atractylenolide III, were not affected by PGR treatment. The amounts of polysaccharides and some internal volatiles were significantly decreased by PGR treatment; while the free amino acids content was generally increased. Fifteen metabolites whose abundance were affected by PGR treatment were identified by UPLC-TOF-MS. Five of the up regulated compounds have been reported to show immune activity, which might contribute to the healing efficacy ("buqi") of C. Radix. The results of this study showed that treatment of C. Radix with PGR during cultivation has economic benefits and affected some main bioactive compounds in C. Radix. PMID- 28991205 TI - Associations between Perceived Neighborhood Walkability and Walking Time, Wellbeing, and Loneliness in Community-Dwelling Older Chinese People in Hong Kong. AB - This study examined the cross-sectional associations between perceived neighborhood walkability and walking time, physical activity, wellbeing, and loneliness, and examined which components of walkability were most strongly associated with better wellbeing and less loneliness in older adults. Participants were community-dwelling Chinese adults aged 60+ (n = 181). Walkability was measured using nine items selected from the Chinese version of the abbreviated Neighborhood Environment Walkability Scales (NEWS) and NEWS for Chinese Seniors. Outcomes were walking time, physical activity, wellbeing (life satisfaction, happiness, sense of purpose and meaning in life), and loneliness. The mean age of the participants was 71.7 +/- 7.8 years. Walkability was positively associated with walking time (p = 0.001, p for trend <0.001) but not with physical activity. After adjusting for socio-demographic characteristics, health conditions, lifestyle, and negative life events, those who perceived their neighborhoods as walkable had higher scores for life satisfaction (p = 0.002) and happiness (p = 0.002), and lower scores for loneliness (p = 0.019), compared with those who perceived their neighborhoods as less walkable. However, perceived neighborhood walkability was not associated with sense of purpose and meaning in life. Among components of walkability, land use mix-access, infrastructure and safety for walking, and traffic safety showed the strongest associations with the measures of wellbeing. The results of this study support the importance of neighborhood walkability for health behavior and wellbeing of older adults. The wellbeing of older adults may be enhanced through the improvement of land use mix access, infrastructure for walking, and traffic safety. PMID- 28991206 TI - Systematic Identification of Machine-Learning Models Aimed to Classify Critical Residues for Protein Function from Protein Structure. AB - Protein structure and protein function should be related, yet the nature of this relationship remains unsolved. Mapping the critical residues for protein function with protein structure features represents an opportunity to explore this relationship, yet two important limitations have precluded a proper analysis of the structure-function relationship of proteins: (i) the lack of a formal definition of what critical residues are and (ii) the lack of a systematic evaluation of methods and protein structure features. To address this problem, here we introduce an index to quantify the protein-function criticality of a residue based on experimental data and a strategy aimed to optimize both, descriptors of protein structure (physicochemical and centrality descriptors) and machine learning algorithms, to minimize the error in the classification of critical residues. We observed that both physicochemical and centrality descriptors of residues effectively relate protein structure and protein function, and that physicochemical descriptors better describe critical residues. We also show that critical residues are better classified when residue criticality is considered as a binary attribute (i.e., residues are considered critical or not critical). Using this binary annotation for critical residues 8 models rendered accurate and non-overlapping classification of critical residues, confirming the multi-factorial character of the structure-function relationship of proteins. PMID- 28991207 TI - Fe Core-Carbon Shell Nanoparticles as Advanced MRI Contrast Enhancer. AB - The aim of this study is to fabricate a hybrid composite of iron (Fe) core-carbon (C) shell nanoparticles with enhanced magnetic properties for contrast enhancement in magnetic resonance imaging (MRI). These new classes of magnetic core-shell nanoparticles are synthesized using a one-step top-down approach through the electric plasma discharge generated in the cavitation field in organic solvents by an ultrasonic horn. Transmission electron microscopy (TEM) observations revealed the core-shell nanoparticles with 10-85 nm in diameter with excellent dispersibility in water without any agglomeration. TEM showed the structural confirmation of Fe nanoparticles with body centered cubic (bcc) crystal structure. Magnetic multi-functional hybrid composites of Fe core-C shell nanoparticles were then evaluated as negative MRI contrast agents, displaying remarkably high transverse relaxivity (r2) of 70 mM-1.S-1 at 7 T. This simple one step synthesis procedure is highly versatile and produces desired nanoparticles with high efficacy as MRI contrast agents and potential utility in other biomedical applications. PMID- 28991208 TI - Wet-Chemical Preparation of TiO2-Based Composites with Different Morphologies and Photocatalytic Properties. AB - TiO2-based composites have been paid significant attention in the photocatalysis field. The size, crystallinity and nanomorphology of TiO2 materials have an important effect on the photocatalytic efficiency. The synthesis and photocatalytic activity of TiO2-based materials have been widely investigated in past decades. Based on our group's research works on TiO2 materials, this review introduces several methods for the fabrication of TiO2, rare-earth-doped TiO2 and noble-metal-decorated TiO2 particles with different morphologies. We focused on the preparation and the formation mechanism of TiO2-based materials with unique structures including spheres, hollow spheres, porous spheres, hollow porous spheres and urchin-like spheres. The photocatalytical activity of urchin-like TiO2, noble metal nanoparticle-decorated 3D (three-dimensional) urchin-like TiO2 and bimetallic core/shell nanoparticle-decorated urchin-like hierarchical TiO2 are briefly discussed. PMID- 28991209 TI - Design, Synthesis and Antifungal Activity of Psoralen Derivatives. AB - A series of linear furanocoumarins with different substituents have been designed and synthesized. Their structures were confirmed by 1H-NMR spectroscopy, high resolution mass spectra (EI-MS), IR, and X-ray single-crystal diffraction. All of the target compounds were evaluated in vitro for their antifungal activity against Rhizoctorzia solani, Botrytis cinerea, Alternaria solani, Gibberella zeae, Cucumber anthrax, and Alternaria leaf spot at 100 MUg/mL, and some of the designed compounds exhibited potential antifungal activities. Compound 3a (67.9%) exhibited higher activity than the control Osthole (66.1%) against Botrytis cinerea. Furthermore, compound 4b (62.4%) represented equivalent antifungal activity as Osthole (69.5%) against Rhizoctonia solani. The structure-activity relationship (SAR) study demonstrates that linear furanocoumarin moiety has an important effect on the antifungal activity, promoting the idea of the coumarin ring as a framework that might be exploited in the future. PMID- 28991210 TI - A Central Bioactive Region of LTBP-2 Stimulates the Expression of TGF-beta1 in Fibroblasts via Akt and p38 Signalling Pathways. AB - Latent transforming growth factor-beta-1 binding protein-2 (LTBP-2) belongs to the LTBP-fibrillin superfamily of extracellular proteins. Unlike other LTBPs, LTBP-2 does not covalently bind transforming growth factor-beta1 (TGF-beta1) but appears to be implicated in the regulation of TGF-beta1 bioactivity, although the mechanisms are largely unknown. In experiments originally designed to study the displacement of latent TGF-beta1 complexes from matrix storage, we found that the addition of exogenous LTBP-2 to cultured human MSU-1.1 fibroblasts caused an increase in TGF-beta1 levels in the medium. However, the TGF-beta1 increase was due to an upregulation of TGF-beta1 expression and secretion rather than a displacement of matrix-stored TGF-beta1. The secreted TGF-beta1 was mainly in an inactive form, and its concentration peaked around 15 h after addition of LTBP-2. Using a series of recombinant LTBP-2 fragments, the bioactivity was identified to a small region of LTBP-2 consisting of an 8-Cys motif flanked by four epidermal growth factor (EGF)-like repeats. The LTBP-2 stimulation of TGF-beta expression involved the phosphorylation of both Akt and p38 mitogen-activated protein kinase (MAPK) signalling proteins, and specific inactivation of each protein individually blocked TGF-beta1 increase. The search for the cell surface receptor mediating this LTBP-2 activity proved inconclusive. Inhibitory antibodies to integrins beta1 and alphaVbeta5 showed no reduction of LTBP-2 stimulation of TGF beta1. However, TGF-beta1 upregulation was partially inhibited by anti alphaVbeta3 integrin antibodies, suggestive of a direct or indirect role for this integrin. Overall, the study indicates that LTBP-2 can directly upregulate cellular TGF-beta1 expression and secretion by interaction with cells via a short central bioactive region. This may be significant in connective tissue disorders involving aberrant TGF-beta1 signalling. PMID- 28991211 TI - Determination of Cadmium in Brown Rice Samples by Fluorescence Spectroscopy Using a Fluoroionophore after Purification of Cadmium by Anion Exchange Resin. AB - Simple analytical methods are needed for determining the cadmium (Cd) content of brown rice samples. In the present study, we developed a new analytical procedure consisting of the digestion of rice using HCl, Cd purification using anion exchange resin, and then determining the Cd content using fluorescence spectroscopy. Digestion with 0.1 M HCl for 10 min at room temperature was sufficient to extract Cd from the ground rice samples. The Cd in the extract was successfully purified in preference to other metals using Dowex 1X8 chloride form resin. Low concentrations of Cd in the eluate could be determined using fluorescence spectroscopy with a fluoroionophore. Overall, the actual limit of quantification value for the Cd content in rice was about 0.1 mg-Cd/kg-rice, which was sufficiently low compared with the regulatory value (0.4 mg-Cd/kg-rice) given by the Codex Alimentarius Commission. We analyzed authentic brown rice samples using our new analytical procedure and the results agreed well with those determined using inductively coupled plasma optical emission spectrometry (ICP OES). Since the fluoroionophore recognized Zn2+ and Hg2+ as well as Cd2+, a sample containing high concentration of Zn2+ or Hg2+ might cause a false positive result. PMID- 28991213 TI - Predictive QSAR Models for the Toxicity of Disinfection Byproducts. AB - Several hundred disinfection byproducts (DBPs) in drinking water have been identified, and are known to have potentially adverse health effects. There are toxicological data gaps for most DBPs, and the predictive method may provide an effective way to address this. The development of an in-silico model of toxicology endpoints of DBPs is rarely studied. The main aim of the present study is to develop predictive quantitative structure-activity relationship (QSAR) models for the reactive toxicities of 50 DBPs in the five bioassays of X Microtox, GSH+, GSH-, DNA+ and DNA-. All-subset regression was used to select the optimal descriptors, and multiple linear-regression models were built. The developed QSAR models for five endpoints satisfied the internal and external validation criteria: coefficient of determination (R2) > 0.7, explained variance in leave-one-out prediction (Q2LOO) and in leave-many-out prediction (Q2LMO) > 0.6, variance explained in external prediction (Q2F1, Q2F2, and Q2F3) > 0.7, and concordance correlation coefficient (CCC) > 0.85. The application domains and the meaning of the selective descriptors for the QSAR models were discussed. The obtained QSAR models can be used in predicting the toxicities of the 50 DBPs. PMID- 28991212 TI - Evaluating the Effects of an Organic Extract from the Mediterranean Sponge Geodia cydonium on Human Breast Cancer Cell Lines. AB - Marine sponges are an excellent source of bioactive secondary metabolites for pharmacological applications. In the present study, we evaluated the chemistry, cytotoxicity and metabolomics of an organic extract from the Mediterranean marine sponge Geodia cydonium, collected in coastal waters of the Gulf of Naples. We identified an active fraction able to block proliferation of breast cancer cell lines MCF-7, MDA-MB231, and MDA-MB468 and to induce cellular apoptosis, whereas it was inactive on normal breast cells (MCF-10A). Metabolomic studies showed that this active fraction was able to interfere with amino acid metabolism, as well as to modulate glycolysis and glycosphingolipid metabolic pathways. In addition, the evaluation of the cytokinome profile on the polar fractions of three treated breast cancer cell lines (compared to untreated cells) demonstrated that this fraction induced a slight anti-inflammatory effect. Finally, the chemical entities present in this fraction were analyzed by liquid chromatography high resolution mass spectrometry combined with molecular networking. PMID- 28991214 TI - Polymethacrylate Coated Electrospun PHB Fibers as a Functionalized Platform for Bio-Diagnostics: Confirmation Analysis on the Presence of Immobilized IgG Antibodies against Dengue Virus. AB - In this article, a combination of far field electrospinning (FFES) and free radical polymerization has been used to create a unique platform for protein immobilization via the physical attachment of biomolecules to the surface of the fiber mats. The large specific surface area of the fibers with its tailored chemistry provides a desirable platform for effective analyte-surface interaction. The detailed analysis of protein immobilization on a newly developed bio-receptive surface plays a vital role to gauge its advantages in bio diagnostic applications. We relied on scanning electron microscopy (SEM), diameter range analysis, and X-ray photoelectron spectroscopy (XPS), along with thermal gravimetric analysis (TGA), water-in-air contact angle analysis (WCA), Fourier transform infrared spectroscopy (FTIR), and atomic force microscopy (AFM) to study our developed platforms and to provide valuable information regarding the presence of biomolecular entities on the surface. Detailed analyses of the fiber mats before and after antibody immobilization have shown obvious changes on the surface of the bioreceptive surface including: (i) an additional peak corresponding to the presence of an antibody in TGA analysis; (ii) extra FTIR peaks corresponding to the presence of antibodies on the coated fiber platforms; and (iii) a clear alteration in surface roughness recorded by AFM analysis. Confirmation analyses on protein immobilization are of great importance as they underlay substantial grounds for various biosensing applications. PMID- 28991216 TI - Adaptive Integration of the Compressed Algorithm of CS and NPC for the ECG Signal Compressed Algorithm in VLSI Implementation. AB - Compressed sensing (CS) is a promising approach to the compression and reconstruction of electrocardiogram (ECG) signals. It has been shown that following reconstruction, most of the changes between the original and reconstructed signals are distributed in the Q, R, and S waves (QRS) region. Furthermore, any increase in the compression ratio tends to increase the magnitude of the change. This paper presents a novel approach integrating the near-precise compressed (NPC) and CS algorithms. The simulation results presented notable improvements in signal-to-noise ratio (SNR) and compression ratio (CR). The efficacy of this approach was verified by fabricating a highly efficient low cost chip using the Taiwan Semiconductor Manufacturing Company's (TSMC) 0.18-MUm Complementary Metal-Oxide-Semiconductor (CMOS) technology. The proposed core has an operating frequency of 60 MHz and gate counts of 2.69 K. PMID- 28991215 TI - Exploring the Degradation of Ibuprofen by Bacillus thuringiensis B1(2015b): The New Pathway and Factors Affecting Degradation. AB - Ibuprofen is one of the most often detected pollutants in the environment, particularly at landfill sites and in wastewaters. Contamination with pharmaceuticals is often accompanied by the presence of other compounds which may influence their degradation. This work describes the new degradation pathway of ibuprofen by Bacillus thuringiensis B1(2015b), focusing on enzymes engaged in this process. It is known that the key intermediate which transformation limits the velocity of the degradation process is hydroxyibuprofen. As the degradation rate also depends on various factors, the influence of selected heavy metals and aromatic compounds on ibuprofen degradation by the B1(2015b) strain was examined. Based on the values of non-observed effect concentration (NOEC) it was found that the toxicity of tested metals increases from Hg(II) < Cu(II) < Cd(II) < Co(II) < Cr(VI). Despite the toxic effect of metals, the biodegradation of ibuprofen was observed. The addition of Co2+ ions into the medium significantly extended the time necessary for the complete removal of ibuprofen. It was shown that Bacillus thuringiensis B1(2015b) was able to degrade ibuprofen in the presence of phenol, benzoate, and 2-chlorophenol. Moreover, along with the removal of ibuprofen, degradation of phenol and benzoate was observed. Introduction of 4-chlorophenol into the culture completely inhibits degradation of ibuprofen. PMID- 28991217 TI - An Efficient and QoS Supported Multichannel MAC Protocol for Vehicular Ad Hoc Networks. AB - Vehicular Ad Hoc Networks (VANETs) employ multichannel to provide a variety of safety and non-safety (transport efficiency and infotainment) applications, based on the IEEE 802.11p and IEEE 1609.4 protocols. Different types of applications require different levels Quality-of-Service (QoS) support. Recently, transport efficiency and infotainment applications (e.g., electronic map download and Internet access) have received more and more attention, and this kind of applications is expected to become a big market driver in a near future. In this paper, we propose an Efficient and QoS supported Multichannel Medium Access Control (EQM-MAC) protocol for VANETs in a highway environment. The EQM-MAC protocol utilizes the service channel resources for non-safety message transmissions during the whole synchronization interval, and it dynamically adjusts minimum contention window size for different non-safety services according to the traffic conditions. Theoretical model analysis and extensive simulation results show that the EQM-MAC protocol can support QoS services, while ensuring the high saturation throughput and low transmission delay for non-safety applications. PMID- 28991218 TI - Furanones and Anthranilic Acid Derivatives from the Endophytic Fungus Dendrothyrium variisporum. AB - Extracts from an endophytic fungus isolated from the roots of the Algerian plant Globularia alypum showed prominent antimicrobial activity in a screening for novel antibiotics. The producer organism was identified as Dendrothyrium variisporum by means of morphological studies and molecular phylogenetic methods. Studies on the secondary metabolite production of this strain in various culture media revealed that the major components from shake flasks were massarilactones D (1) and H (2) as well as two new furanone derivatives for which we propose the trivial names (5S)-cis-gregatin B (3) and graminin D (4). Scale-up of the fermentation in a 10 L bioreactor yielded massarilactone D and several further metabolites. Among those were three new anthranilic acid derivatives (5-7), two known anthranilic acid analogues (8 and 9) and three cyclopeptides (10-12). Their structures were elucidated on the basis of extensive spectroscopic analysis (1D- and 2D-NMR), high-resolution mass spectrometry (HRESIMS), and the application of the modified Mosher's method. The isolated metabolites were tested for antimicrobial and cytotoxic activities against various bacteria, fungi, and two mammalian cell lines. The new Metabolite 5 and Compound 9 exhibited antimicrobial activity while Compound 9 showed cytotoxicity activity against KB3.1 cells. PMID- 28991219 TI - Distributions and Sources of Polycyclic Aromatic Hydrocarbons (PAHs) in Soils around a Chemical Plant in Shanxi, China. AB - Background: Yearly the Shanxi coal chemical industry extracts many coal resources, producing at the same time many polycyclic aromatic hydrocarbons (PAHs) that are emitted as by-products of coal incomplete combustion. Methods: Sixty-six soil samples collected from 0 to 100 cm vertical sections of three different agricultural (AS), roadside (RS) and park (PS) functional soils around a chemical plant in Shanxi, China were analyzed for the presence of the 16 priority control PAHs. Results: The total concentrations (?16PAHs) varied in a range of 35.4-116 mg/kg, 5.93-66.5 mg/kg and 3.87-76.0 mg/kg for the RS, PS and AS surface soil, respectively, and 5-ring PAHs were found to be dominant (44.4 49.0%), followed by 4-ring PAHs (15.9-24.5%). Moreover, the average value of ?16PAHs decreased with the depth, 7.87 mg/kg (0-25 cm), 4.29 mg/kg (25-50 cm), 3.00 mg/kg (50-75 cm), 2.64 mg/kg (75-100 cm) respectively, in PS and AS soil vertical sections. Conclusions: The PAH levels in the studied soils were the serious contamination level (over 1.00 mg/kg) according to the Soils Quality Guidelines. The carcinogenic PAHs (SigmaBPAHsBapeq) were approximately 14.8 times higher than the standard guideline level (0.60 mg/kg) and 90.3% of PAHs were produced by coal/wood/grass combustion processes. PMID- 28991220 TI - Wireless Biological Electronic Sensors. AB - The development of wireless biological electronic sensors could open up significant advances for both fundamental studies and practical applications in a variety of areas, including medical diagnosis, environmental monitoring, and defense applications. One of the major challenges in the development of wireless bioelectronic sensors is the successful integration of biosensing units and wireless signal transducers. In recent years, there are a few types of wireless communication systems that have been integrated with biosensing systems to construct wireless bioelectronic sensors. To successfully construct wireless biological electronic sensors, there are several interesting questions: What types of biosensing transducers can be used in wireless bioelectronic sensors? What types of wireless systems can be integrated with biosensing transducers to construct wireless bioelectronic sensors? How are the electrical sensing signals generated and transmitted? This review will highlight the early attempts to address these questions in the development of wireless biological electronic sensors. PMID- 28991222 TI - Nutrient-extraction blender preparation reduces postprandial glucose responses from fruit juice consumption. AB - Although whole-fruit consumption is regarded as protective against type 2 diabetes (T2DM), conventionally prepared fruit juice is associated with increased T2DM risk, and current public health advice recommends its restriction. 'Nutrient extractor' style blenders are increasing in popularity worldwide as an alternative means of juicing fruit, but little is known about their effect on postprandial glucose levels. The current study investigated the effect of nutrient extraction on postprandial blood glucose response and glycemic index (GI) compared with a glucose control for both mixed fruit and a high GI fruit (mango). Remarkably, consumption of nutrient-extracted mixed fruit resulted in a significant lowering of the GI (32.7+/-8.5) compared with whole mixed fruit (66.2+/-8.2, P<0.05). For the high GI mango, there were no differences between nutrient-extracted and whole fruit, indicating that even for a high GI fruit the effect of nutrient extraction does not increase GI compared with the whole fruit. These findings suggest that, in contrast to conventionally prepared fruit juice, fruit juice prepared by nutrient extraction in some cases elicits a more favorable postprandial glycemic response than whole fruit and even for high GI fruits do not worsen the response. The mechanism responsible for this effect is currently unclear. However, these results suggest that fruit homogenized by nutrient extraction should be considered as a potential dietetic strategy for glycemic control. PMID- 28991221 TI - A non-coding function of TYRP1 mRNA promotes melanoma growth. AB - Competition among RNAs to bind miRNA is proposed to influence biological systems. However, the role of this competition in disease onset is unclear. Here, we report that TYRP1 mRNA, in addition to encoding tyrosinase-related protein 1 (TYRP1), indirectly promotes cell proliferation by sequestering miR-16 on non canonical miRNA response elements. Consequently, the sequestered miR-16 is no longer able to repress its mRNA targets, such as RAB17, which is involved in melanoma cell proliferation and tumour growth. Restoration of miR-16 tumour suppressor function can be achieved in vitro by silencing TYRP1 or increasing miR 16 expression. Importantly, TYRP1-dependent miR-16 sequestration can also be overcome in vivo by using small oligonucleotides that mask miR-16-binding sites on TYRP1 mRNA. Together, our findings assign a pathogenic non-coding function to TYRP1 mRNA and highlight miRNA displacement as a promising targeted therapeutic approach for melanoma. PMID- 28991223 TI - Merkel cell polyomavirus small T antigen induces genome instability by E3 ubiquitin ligase targeting. AB - This corrects the article DOI: 10.1038/onc.2017.277. PMID- 28991224 TI - Resistin facilitates breast cancer progression via TLR4-mediated induction of mesenchymal phenotypes and stemness properties. AB - Growing evidence indicates that resistin-an obesity-related cytokine-is upregulated in breast cancer patients, yet its impact on breast cancer behavior remains to be ascertained. Similarly, Toll-like receptor 4 (TLR4) has been implicated in breast cancer progression, however, its clinically relevant endogenous ligand remains elusive. In this study, we observed that high serum resistin levels in breast cancer patients positively correlated with tumor stage, size and lymph node metastasis. These findings were replicated in animal models of breast cancer tumorigenesis and metastasis. Resistin was found to promote epithelial-mesenchymal transition and stemness in breast cancer cells-mechanisms critical to tumorigenesis and metastasis-through a TLR4/nuclear factor kappa light-chain-enhancer of activated B cells (NF-kappaB)/signal transducer and activator of transcription 3 (STAT3) signaling pathway and negated by TLR4 specific antibody and antagonist. These findings provide clear evidence that resistin is a clinically relevant endogenous ligand for TLR4, which promotes tumor progression via TLR4/NF-kappaB/STAT3 signaling, providing insights into a novel therapeutic target in breast cancer. PMID- 28991225 TI - Super-enhancers define a proliferative PGC-1alpha-expressing melanoma subgroup sensitive to BET inhibition. AB - Metabolic changes are linked to epigenetic reprogramming and play important roles in several tumor types. PGC-1alpha is a transcriptional coactivator controlling mitochondrial biogenesis and is linked to oxidative phosphorylation. We provide evidence that melanoma models with elevated PGC-1alpha levels are characteristic of the proliferative phenotype and are sensitive to bromodomain and extra terminal domain (BET) inhibitor treatment. A super-enhancer region highly occupied by the BET family member BRD4 was identified for the PGC-1alpha gene. BET inhibitor treatment prevented this interaction, leading to a dramatic reduction of PGC-1alpha expression. Accordingly, BET inhibition diminished respiration and mitochondrial function in cells. In vivo, melanoma models with high PGC-1alpha expression strongly responded to BET inhibition by reduction of PGC-1alpha and impaired tumor growth. Altogether, our findings identify epigenetic regulatory elements that define a subset of melanomas with high sensitivity to BET inhibition, which opens up the opportunity to define melanoma patients most likely to respond to this treatment, depending on their tumor characteristics. PMID- 28991226 TI - LSD1 promotes S-phase entry and tumorigenesis via chromatin co-occupation with E2F1 and selective H3K9 demethylation. AB - Histone H3 lysine-9 (H3K9) methylation is essential for retinoblastoma protein (RB)-mediated heterochromatin formation, epigenetic silencing of S-phase genes and permanent cell cycle arrest or cellular senescence. Besides as an H3K4 demethylase, lysine-specific demethylase-1 (LSD1) has been shown to promote H3K9 demethylation. However, it is unexplored whether LSD1 has a causal role in regulating cell cycle entry and senescence. Here we demonstrate that genetic depletion or pharmacological inhibition of LSD1 triggers G1 arrest and cellular senescence. Genome-wide chromatin immunoprecipitation-sequencing analysis reveals that LSD1 binding sites overlap significantly with those bound by the S-phase gene transcription factor E2F1. Gene ontology analysis demonstrates that a large portion of E2F1 and LSD1 cotargeted genes are involved in cell cycle and proliferation. Further analyses show that depletion of LSD1 increases the level of H3K9me2 and thereby represses expression of the LSD1-E2F1 cotarget genes, but has no effects on H3K4me2 level in those loci. In contrast, knockdown of the H3K4me2 reader PHF8 decreases the H3K4me2 level at the LSD1-E2F1 cotargeted loci, but this effect is rescued by codepletion of LSD1. Furthermore, the enzymatic activity of LSD1 is essential for H3K9me2 demethylation at cell cycle gene loci. Notably, cotreatment of chemotherapeutic agent camptothecin enhanced LSD1 inhibitor-induced senescence and growth inhibition of cancer cells in vitro and in mice. Our data reveal LSD1 as a molecular rheostat selectively regulating H3K9 demethylation at cell cycle gene loci, thereby representing a key player in oncogenesis and a viable target for cancer therapy. PMID- 28991227 TI - Essential role of METTL3-mediated m6A modification in glioma stem-like cells maintenance and radioresistance. AB - Despite advances in biology and therapeutic modalities, existence of highly tumorigenic glioma stem-like cells (GSCs) makes glioblastomas (GBMs) invincible. N6-methyl adenosine (m6A), one of the abundant mRNA modifications catalyzed by methyltransferase-like 3 and 14 (METTL3/14), influences various events in RNA metabolism. Here, we report the crucial role of METTL3-mediated m6A modification in GSC (neurosphere) maintenance and dedifferentiation of glioma cells. METTL3 expression is elevated in GSC and attenuated during differentiation. RNA immunoprecipitation studies identified SOX2 as a bonafide m6A target of METTL3 and the m6A modification of SOX2 mRNA by METTL3 enhanced its stability. The exogenous overexpression of 3'UTR-less SOX2 significantly alleviated the inhibition of neurosphere formation observed in METTL3 silenced GSCs. METTL3 binding and m6A modification in vivo required intact three METTL3/m6A sites present in the SOX2-3'UTR. Further, we found that the recruitment of Human antigen R (HuR) to m6A-modified RNA is essential for SOX2 mRNA stabilization by METTL3. In addition, we found a preferential binding by HuR to the m6A-modified transcripts globally. METTL3 silenced GSCs showed enhanced sensitivity to gamma irradiation and reduced DNA repair as evidenced from the accumulation of gamma H2AX. Exogenous overexpression of 3'UTR-less SOX2 in METTL3 silenced GSCs showed efficient DNA repair and also resulted in the significant rescue of neurosphere formation from METTL3 silencing induced radiosensitivity. Silencing METTL3 inhibited RasV12 mediated transformation of mouse immortalized astrocytes. GBM tumors have elevated levels of METTL3 transcripts and silencing METTL3 in U87/TIC inhibited tumor growth in an intracranial orthotopic mouse model with prolonged mice survival. METTL3 transcript levels predicted poor survival in GBMs which are enriched for GSC-specific signature. Thus our study reports the importance of m6A modification in GSCs and uncovers METTL3 as a potential molecular target in GBM therapy. PMID- 28991228 TI - Deletion of Menin in craniofacial osteogenic cells in mice elicits development of mandibular ossifying fibroma. AB - Ossifying fibroma (OF) is a rare benign tumor of the craniofacial bones that can reach considerable and disfiguring dimensions if left untreated. Although the clinicopathological characteristics of OF are well established, the underlying etiology has remained largely unknown. Our work indicates that Men1-a tumor suppressor gene responsible of Multiple endocrine neoplasia type 1-is critical for OF formation and shows that mice with targeted disruption of Men1 in osteoblasts (Men1Runx2Cre) develop multifocal OF in the mandible with a 100% penetrance. Using lineage-tracing analysis, we demonstrate that loss of Men1 arrests stromal osteoprogenitors in OF at the osterix-positive pre-osteoblastic differentiation stage. Analysis of Men1-lacking stromal spindle cells isolated from OF (OF-derived MSCs (OFMSCs)) revealed a downregulation of the cyclin dependent kinase (CDK) inhibitor Cdkn1a, consistent with an increased proliferation rate. Intriguingly, the re-expression of Men1 in Men1-deficient OFMSCs restored Cdkn1a expression and abrogated cellular proliferation supporting the tumor-suppressive role of Men1 in OF. Although our work presents the first evidence of Men1 in OF development, it further provides the first genetic mouse model of OF that can be used to better understand the molecular pathogenesis of these benign tumors and to potentially develop novel treatment strategies. PMID- 28991229 TI - Hypoxia activates cadherin-22 synthesis via eIF4E2 to drive cancer cell migration, invasion and adhesion. AB - Hypoxia is a driver of cell movement in processes such as development and tumor progression. The cellular response to hypoxia involves a transcriptional program mediated by hypoxia-inducible factors, but translational control has emerged as a significant contributor. In this study, we demonstrate that a cell-cell adhesion molecule, cadherin-22, is upregulated in hypoxia via mTORC1-independent translational control by the initiation factor eIF4E2. We identify new functions of cadherin-22 as a hypoxia-specific cell-surface molecule involved in cancer cell migration, invasion and adhesion. Silencing eIF4E2 or cadherin-22 significantly impaired MDA-MB-231 breast carcinoma and U87MG glioblastoma cell migration and invasion only in hypoxia, while reintroduction of the respective exogenous gene restored the normal phenotype. Cadherin-22 was evenly distributed throughout spheroids and required for their formation and support of a hypoxic core. Conversely, E-cadherin translation was repressed by hypoxia and only expressed in the oxygenated cells of U87MG spheroids. Furthermore, immunofluorescence on paraffin-embedded human tissue from 40 glioma and 40 invasive ductal breast carcinoma patient specimens revealed that cadherin-22 expression colocalized with areas of hypoxia and significantly correlated with tumor grade and progression-free survival or stage and tumor size, respectively. This study broadens our understanding of tumor progression and metastasis by highlighting cadherin-22 as a potential new target of cancer therapy to disable hypoxic cancer cell motility and adhesion. PMID- 28991230 TI - Alu RNA accumulation induces epithelial-to-mesenchymal transition by modulating miR-566 and is associated with cancer progression. AB - Alu sequences are the most abundant short interspersed repeated elements in the human genome. Here we show that in a cell culture model of colorectal cancer (CRC) progression, we observe accumulation of Alu RNA that is associated with reduced DICER1 levels. Alu RNA induces epithelial-to-mesenchymal transition (EMT) by acting as a molecular sponge of miR-566. Moreover, Alu RNA accumulates as consequence of DICER1 deficit in colorectal, ovarian, renal and breast cancer cell lines. Interestingly, Alu RNA knockdown prevents DICER1 depletion-induced EMT despite global microRNA (miRNA) downregulation. Alu RNA expression is also induced by transforming growth factor-beta1, a major driver of EMT. Corroborating this data, we found that non-coding Alu RNA significantly correlates with tumor progression in human CRC patients. Together, these findings reveal an unexpected DICER1-dependent, miRNA-independent role of Alu RNA in cancer progression that could bring mobile element transcripts in the fields of cancer therapeutic and prognosis. PMID- 28991231 TI - Slug/Pcad pathway controls epithelial cell dynamics in mammary gland and breast carcinoma. AB - Mammary gland morphogenesis results from the coordination of proliferation, cohort migration, apoptosis and stem/progenitor cell dynamics. We showed earlier that the transcription repressor Slug is involved in these functions during mammary tubulogenesis. Slug is expressed by a subpopulation of basal epithelial cells, co-expressed with P-cadherin (Pcad). Slug-knockout mammary glands showed excessive branching, similarly to Pcad-knockout. Here, we found that Slug unexpectedly binds and activates Pcad promoter through E-boxes, inducing Pcad expression. We determined that Pcad can mediate several functions of Slug: Pcad promoted clonal mammosphere growth, basal epithelial differentiation, cell-cell dissociation and cell migration, rescuing Slug depletion. Pcad also promoted cell migration in isolated cells, in association with Src activation, focal adhesion reorganization and cell polarization. Pcad, similarly to Slug, was required for in vitro 3D tubulogenesis. Therefore, Pcad appears to be responsible for epithelial-mesenchymal transition-linked plasticity in mammary epithelial cells. In addition, we found that genes from the Slug/Pcad pathway components were co expressed and specifically correlated in human breast carcinomas subtypes, carrying pathophysiological significance. PMID- 28991232 TI - The extracellular matrix protein mindin attenuates colon cancer progression by blocking angiogenesis via Egr-1-mediated regulation. AB - Mindin, a secreted, highly conserved extracellular matrix (ECM) protein, exerts a broad spectrum of effects on the innate immune system. However, its function in colorectal cancer (CRC) progression is not well established, and its upstream regulation mechanisms remain unclear. Contrary to previous reports, this study used two different enzyme-linked immunosorbent assay (ELISA) kits to show that the serum level of mindin was significantly decreased in CRC patients and that this decreased level is more significantly associated with the early stages of the disease. To explore the regulation of mindin, we used a bioinformatics approach to predict potential transcription factors and determined that early growth response factor (Egr)-1 directly regulates mindin expression at the transcriptional level using dual luciferase, chromatin immunoprecipitation (ChIP) DNA and electrophoretic mobility shift assay (EMSA) methods. Egr-1 regulates mindin mRNA and protein expression in CRC cells, and the protein expression of both Egr-1 and mindin was significantly decreased in tumor lesions of patients compared with adjacent control tissues. Mindin is essential for Egr-1-mediated inhibition of endothelial cell tube formation, and mindin inhibits endotheliocyte proliferation, migration and angiogenic sprouts in vitro. Overexpression of mindin suppressed xenograft tumor growth by blocking angiogenesis instead of directly suppressing CRC cell proliferation. Mechanically, mindin inhibits the hypoxia-induced HIF-1a and VEGFA protein expression in CRC cells and the phosphorylation of VEGFR-2 in endothelial cells. The results suggest that the serum level of mindin can be used as a novel biomarker for early detection of CRC and that the Egr-1/mindin axis is a potential therapeutic target for the inhibition of angiogenesis in CRC development. PMID- 28991233 TI - DNA methylation aberrancies delineate clinically distinct subsets of colorectal cancer and provide novel targets for epigenetic therapies. AB - Colorectal cancer (CRC) is a worldwide health concern with respect to both incidence and mortality, and as a result, CRC tumorigenesis, progression and metastasis have been heavily studied, especially with respect to identifying genetic, epigenetic, transcriptomic and proteomic profiles of disease. DNA methylation alterations are hallmarks of CRC, and epigenetic driver genes have been identified that are thought to be involved in early stages of tumorigenesis. Moreover, distinct CRC patient subgroups are organized based on DNA methylation profiles. CRC tumors displaying CpG island methylator phenotypes (CIMPs), defined as DNA hypermethylation at specific CpG islands in subsets of tumors, show high concordance with specific genetic alterations, disease risk factors and patient outcome. This review details the DNA methylation alterations in CRC, the significance of CIMP status, the development of treatments based on specific molecular profiles and the application of epigenetic therapies for CRC patient treatment. PMID- 28991234 TI - DHX15 promotes prostate cancer progression by stimulating Siah2-mediated ubiquitination of androgen receptor. AB - Androgen receptor (AR) activation is critical for prostate cancer (PCa) development and progression, including castration resistance. The nuclear export signal of AR (NESAR) has an important role in AR intracellular trafficking and proteasome-dependent degradation. Here, we identified the RNA helicase DHX15 as a novel AR co-activator using a yeast mutagenesis screen and revealed that DHX15 regulates AR activity by modulating E3 ligase Siah2-mediated AR ubiquitination independent of its ATPase activity. DHX15 and Siah2 form a complex with AR, through NESAR. DHX15 stabilized Siah2 and enhanced its E3 ubiquitin-ligase activity, resulting in AR activation. Importantly, DHX15 was upregulated in PCa specimens and its expression was correlated with Gleason scores and prostate specific antigen recurrence. Furthermore, DHX15 immunostaining correlated with Siah2. Finally, DHX15 knockdown inhibited the growth of C4-2 prostate tumor xenografts in mice. Collectively, our data argue that DHX15 enhances AR transcriptional activity and contributes to PCa progression through Siah2. PMID- 28991236 TI - Corrigendum: An ethnically relevant consensus Korean reference genome is a step towards personal reference genomes. AB - This corrects the article DOI: 10.1038/ncomms13637. PMID- 28991237 TI - Corrigendum: Engineering and optimising deaminase fusions for genome editing. AB - This corrects the article DOI: 10.1038/ncomms13330. PMID- 28991235 TI - Circular RNAs in cancer: opportunities and challenges in the field. AB - Circular RNA (circRNA) is a novel member of the noncoding cancer genome with distinct properties and diverse cellular functions, which is being explored at a steadily increasing pace. The list of endogenous circRNAs involved in cancer continues to grow; however, the functional relevance of the vast majority is yet to be discovered. In general, circRNAs are exceptionally stable molecules and some have been shown to function as efficient microRNA sponges with gene regulatory potential. Many circRNAs are highly conserved and have tissue-specific expression patterns, which often do not correlate well with host gene expression. Here we review the current knowledge on circRNAs in relation to their implications in tumorigenesis as well as their potential as diagnostic and prognostic biomarkers and as possible therapeutic targets in future personalized medicine. Finally, we discuss future directions for circRNA cancer research and current caveats, which must be addressed to facilitate the translation of basic circRNA research into clinical use. PMID- 28991238 TI - The structure-energy landscape of NMDA receptor gating. AB - N-Methyl-D-aspartate (NMDA) receptors are the main calcium-permeable excitatory receptors in the mammalian central nervous system. The NMDA receptor gating is complex, exhibiting multiple closed, open, and desensitized states; however, central questions regarding the conformations and energetics of the transmembrane domains as they relate to the gating states are still unanswered. Here, using single-molecule Forster resonance energy transfer (smFRET), we map the energy landscape of the first transmembrane segment of the Rattus norvegicus NMDA receptor under resting and various liganded conditions. These results show kinetically and structurally distinct changes associated with apo, agonist-bound, and inhibited receptors linked by a linear mechanism of gating at this site. Furthermore, the smFRET data suggest that allosteric inhibition by zinc occurs by an uncoupling of the agonist-induced changes at the extracellular domains from the gating motions leading to an apo-like state, while dizocilpine, a pore blocker, stabilizes multiple closely packed transmembrane states. PMID- 28991241 TI - Multifunctional high-performance van der Waals heterostructures. AB - A range of novel two-dimensional materials have been actively explored for More Moore and More-than-Moore device applications because of their ability to form van der Waals heterostructures with unique electronic properties. However, most of the reported electronic devices exhibit insufficient control of multifunctional operations. Here, we leverage the band-structure alignment properties of narrow-bandgap black phosphorus and large-bandgap molybdenum disulfide to realize vertical heterostructures with an ultrahigh rectifying ratio approaching 106 and on-off ratio up to 107. Furthermore, we design and fabricate tunable multivalue inverters, in which the output logic state and window of the mid-logic can be controlled by specific pairs of channel length and, most importantly, by the electric field, which shifts the band-structure alignment across the heterojunction. Finally, high gains over 150 are achieved in the inverters with optimized device geometries, showing great potential for future logic applications. PMID- 28991242 TI - Hot carrier-enhanced interlayer electron-hole pair multiplication in 2D semiconductor heterostructure photocells. AB - Strong electronic interactions can result in novel particle-antiparticle (electron-hole, e-h) pair generation effects, which may be exploited to enhance the photoresponse of nanoscale optoelectronic devices. Highly efficient e-h pair multiplication has been demonstrated in several important nanoscale systems, including nanocrystal quantum dots, carbon nanotubes and graphene. The small Fermi velocity and nonlocal nature of the effective dielectric screening in ultrathin layers of transition-metal dichalcogenides (TMDs) indicates that e-h interactions are very strong, so high-efficiency generation of e-h pairs from hot electrons is expected. However, such e-h pair multiplication has not been observed in 2D TMD devices. Here, we report the highly efficient multiplication of interlayer e-h pairs in 2D semiconductor heterostructure photocells. Electronic transport measurements of the interlayer I-VSD characteristics indicate that layer-indirect e-h pairs are generated by hot-electron impact excitation at temperatures near T = 300 K. By exploiting this highly efficient interlayer e-h pair multiplication process, we demonstrate near-infrared optoelectronic devices that exhibit 350% enhancement of the optoelectronic responsivity at microwatt power levels. Our findings, which demonstrate efficient carrier multiplication in TMD-based optoelectronic devices, make 2D semiconductor heterostructures viable for a new class of ultra-efficient photodetectors based on layer-indirect e-h excitations. PMID- 28991239 TI - Stendomycin selectively inhibits TIM23-dependent mitochondrial protein import. AB - Tim17 and Tim23 are the main subunits of the TIM23 complex, one of the two major essential mitochondrial inner-membrane protein translocon machineries (TIMs). No chemical probes that specifically inhibit TIM23-dependent protein import were known to exist. Here we show that the natural product stendomycin, produced by Streptomyces hygroscopicus, is a potent and specific inhibitor of the TIM23 complex in yeast and mammalian cells. Furthermore, stendomycin-mediated blockage of the TIM23 complex does not alter normal processing of the major regulatory mitophagy kinase PINK1, but TIM23 is required to stabilize PINK1 on the outside of mitochondria to initiate mitophagy upon membrane depolarization. PMID- 28991240 TI - Polypharmacology-based ceritinib repurposing using integrated functional proteomics. AB - Targeted drugs are effective when they directly inhibit strong disease drivers, but only a small fraction of diseases feature defined actionable drivers. Alternatively, network-based approaches can uncover new therapeutic opportunities. Applying an integrated phenotypic screening, chemical and phosphoproteomics strategy, here we describe the anaplastic lymphoma kinase (ALK) inhibitor ceritinib as having activity across several ALK-negative lung cancer cell lines and identify new targets and network-wide signaling effects. Combining pharmacological inhibitors and RNA interference revealed a polypharmacology mechanism involving the noncanonical targets IGF1R, FAK1, RSK1 and RSK2. Mutating the downstream signaling hub YB1 protected cells from ceritinib. Consistent with YB1 signaling being known to cause taxol resistance, combination of ceritinib with paclitaxel displayed strong synergy, particularly in cells expressing high FAK autophosphorylation, which we show to be prevalent in lung cancer. Together, we present a systems chemical biology platform for elucidating multikinase inhibitor polypharmacology mechanisms, subsequent design of synergistic drug combinations, and identification of mechanistic biomarker candidates. PMID- 28991243 TI - Third International workshop on the biology, prevention, and treatment of relapse after stem cell transplantation. PMID- 28991244 TI - Early consolidation with high-dose therapy and autologous stem cell transplantation is a feasible and effective treatment option in HIV-associated non-Hodgkin lymphoma at high risk. PMID- 28991245 TI - Secondary solid cancer following hematopoietic cell transplantation in patients with thalassemia major. AB - Hematopoietic cell transplant (HCT) recipients have a substantial risk of developing secondary solid cancers (SSCs). The aim of this retrospective study was to compare the incidence of SSC in a monocentric cohort of thalassemia major (TM) patients (n=122) who received HCT versus an hematopoietic cell donor monocentric cohort (n=122) and versus a large multicenter cohort of age- and sex matched TM patients (n=244) who received conventional therapy. With a median follow-up of 24 years, 8 transplanted patients were diagnosed with SSC at a median of 18 years after HCT and at a median age of 33 years. Three patients died of cancer progression and 5 are living after a follow-up ranging from 10 months to 16 years after SSC diagnosis. The 30-year cumulative incidence of developing SSC was 13.24%. The occurrence of solid cancers in the hematopoietic cell donor cohort was limited to only one case for a significantly lower cumulative incidence (3.23%, P=0.02) and to 3 cases in the cohort of nontransplant patients for a significantly lower cumulative incidence (1.32%, P=0.005). This study shows that the magnitude of increased risk of SST is fourfold to sixfold for patients treated with HCT as compared with hematopoietic cell donors and nontransplant patients. PMID- 28991246 TI - Importance of conditioning regimen intensity, MRD positivity, and KIR ligand mismatch in UCB transplantation. PMID- 28991248 TI - Johannes Joseph van Rood: pioneer in immuno-genetics (7 April 1926-21 July 2017). PMID- 28991249 TI - Donor cell-derived transient abnormal myelopoiesis as a specific complication of umbilical cord blood transplantation. PMID- 28991247 TI - Long-term prognosis for 1-year relapse-free survivors of CD34+ cell-selected allogeneic hematopoietic stem cell transplantation: a landmark analysis. AB - CD34+ cell selection significantly improves GvHD-free survival in allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, specific information regarding long-term prognosis and risk factors for late mortality after CD34+ cell-selected allo-HSCT is lacking. We conducted a single-center landmark analysis in 276 patients alive without relapse 1 year after CD34+ cell selected allo-HSCT for AML (n=164), ALL (n=33) or myelodysplastic syndrome (n=79). At 5 years' follow-up after the 1-year landmark (range 0.03-13 years), estimated relapse-free survival (RFS) was 73% and overall survival (OS) 76%. The 5-year cumulative incidence of relapse and non-relapse mortality (NRM) were 11% and 16%, respectively. In multivariate analysis, Hematopoietic Cell Transplantation Comorbidity Index score?3 correlated with marginally worse RFS (hazard ratio (HR) 1.78, 95% confidence interval (CI) 0.97-3.28, P=0.06) and significantly worse OS (HR 2.53, 95% CI 1.26-5.08, P=0.004). Despite only 24% of patients with acute GvHD within 1 year, this also significantly correlated with worse RFS and OS, with increasing grades of acute GvHD associating with increasingly poorer survival on multivariate analysis (P<0.0001). Of 63 deaths after the landmark, GvHD accounted for 27% of deaths and was the most common cause of late mortality, followed by relapse and infection. Although prognosis is excellent for patients alive without relapse 1 year after CD34+ cell-selected allo-HSCT, risks of late relapse and NRM persist, particularly due to GvHD. PMID- 28991250 TI - Assessment of TREC, KREC and telomere length in long-term survivors after allogeneic HSCT: the role of GvHD and graft source and evidence for telomere homeostasis in young recipients. AB - Reconstitution of the adaptive immune system following allogeneic hematopoietic stem cell transplantation is crucial for beneficial outcome and is affected by several factors, such as GvHD and graft source. The impact of these factors on immune reconstitution has been thoroughly investigated during the early phase after transplantation. However, little is known about their long-term effect. Similarly, leukocyte telomere length (TL) shortening has been reported shortly after transplantation. Nevertheless, whether TL shortening continues in long-term aspect is still unsettled. Here, we assessed T-cell receptor excision circle (TREC), kappa deleting recombination excision circle (KREC) and leukocyte TL in recipients and donors several years post transplantation (median 17 years). Our analysis showed that, recipients who received bone marrow (BM) as the graft source have higher levels of both TREC and KREC. Also, chronic GvHD affected TREC levels and TL but not KREC levels. Finally, we show that recipient's TL was longer than respective donors in a group of young age recipients with high KREC levels. Our results suggest that BM can be beneficial for long-term adaptive immune recovery. We also present supporting evidence for recipient telomere homeostasis, especially in young age recipients, rather than telomere shortening. PMID- 28991251 TI - Lack of association between relationship status and clinical outcome in allogeneic stem cell transplantation-the Swiss Transplant Cohort Study. PMID- 28991252 TI - Population pharmacokinetics and pharmacodynamics of mycophenolic acid using the prospective data in patients undergoing hematopoietic stem cell transplantation. AB - Mycophenolate mofetil (MMF), a prodrug of mycophenolic acid (MPA), is used to suppress GvHD in patients undergoing hematopoietic stem cell transplantation (HCT). The purpose of this study was to construct a population pharmacokinetic and pharmacodynamic model in HCT patients for individualized MPA therapy. Blood samples were obtained from 49 HCT patients after starting MMF therapy. Population pharmacokinetic and pharmacodynamic parameters were obtained using the program NONMEM. MPA was described via a one-compartment model with a first-order elimination, and 30.9% of MPA glucuronide (MPAG) was found in the enterohepatic circulation. Inosine-5'-monophosphate dehydrogenase (IMPDH) activity was modeled as a maximal inhibitory model with a half-maximal inhibitory concentration (IC50) of 3.59 MUg/mL against MPA concentrations. Simulations based on the obtained pharmacokinetic and pharmacodynamic parameters revealed that decreased creatinine clearance increases the MPAG concentration followed by an increased MPA concentration; therefore, IMPDH activity decreases. Diarrhea decreases the enterohepatic circulation of MPAG and consequently reduces MPA concentration. The IC50 for MPA exhibited a positive association with C-reactive protein. Dosage adjustment based on plasma MPA concentration is required especially for patients with renal dysfunction and/or diarrhea. PMID- 28991253 TI - Allogeneic stem cell transplantation for non-de novo AML or advanced myelodysplastic syndromes: influence of GvHD and donor lymphocyte infusions on long-term outcome. PMID- 28991254 TI - The draft genome of tropical fruit durian (Durio zibethinus). AB - Durian (Durio zibethinus) is a Southeast Asian tropical plant known for its hefty, spine-covered fruit and sulfury and onion-like odor. Here we present a draft genome assembly of D. zibethinus, representing the third plant genus in the Malvales order and first in the Helicteroideae subfamily to be sequenced. Single molecule sequencing and chromosome contact maps enabled assembly of the highly heterozygous durian genome at chromosome-scale resolution. Transcriptomic analysis showed upregulation of sulfur-, ethylene-, and lipid-related pathways in durian fruits. We observed paleopolyploidization events shared by durian and cotton and durian-specific gene expansions in MGL (methionine gamma-lyase), associated with production of volatile sulfur compounds (VSCs). MGL and the ethylene-related gene ACS (aminocyclopropane-1-carboxylic acid synthase) were upregulated in fruits concomitantly with their downstream metabolites (VSCs and ethylene), suggesting a potential association between ethylene biosynthesis and methionine regeneration via the Yang cycle. The durian genome provides a resource for tropical fruit biology and agronomy. PMID- 28991255 TI - Patient-derived xenografts undergo mouse-specific tumor evolution. AB - Patient-derived xenografts (PDXs) have become a prominent cancer model system, as they are presumed to faithfully represent the genomic features of primary tumors. Here we monitored the dynamics of copy number alterations (CNAs) in 1,110 PDX samples across 24 cancer types. We observed rapid accumulation of CNAs during PDX passaging, often due to selection of preexisting minor clones. CNA acquisition in PDXs was correlated with the tissue-specific levels of aneuploidy and genetic heterogeneity observed in primary tumors. However, the particular CNAs acquired during PDX passaging differed from those acquired during tumor evolution in patients. Several CNAs recurrently observed in primary tumors gradually disappeared in PDXs, indicating that events undergoing positive selection in humans can become dispensable during propagation in mice. Notably, the genomic stability of PDXs was associated with their response to chemotherapy and targeted drugs. These findings have major implications for PDX-based modeling of human cancer. PMID- 28991256 TI - Genome-wide association analysis identifies 30 new susceptibility loci for schizophrenia. AB - We conducted a genome-wide association study (GWAS) with replication in 36,180 Chinese individuals and performed further transancestry meta-analyses with data from the Psychiatry Genomics Consortium (PGC2). Approximately 95% of the genome wide significant (GWS) index alleles (or their proxies) from the PGC2 study were overrepresented in Chinese schizophrenia cases, including ~50% that achieved nominal significance and ~75% that continued to be GWS in the transancestry analysis. The Chinese-only analysis identified seven GWS loci; three of these also were GWS in the transancestry analyses, which identified 109 GWS loci, thus yielding a total of 113 GWS loci (30 novel) in at least one of these analyses. We observed improvements in the fine-mapping resolution at many susceptibility loci. Our results provide several lines of evidence supporting candidate genes at many loci and highlight some pathways for further research. Together, our findings provide novel insight into the genetic architecture and biological etiology of schizophrenia. PMID- 28991258 TI - Vertical inhibition of the PI3K/Akt/mTOR pathway is synergistic in breast cancer. AB - Deregulation and activation of the phosphoinositide 3-kinase (PI3K)/Akt/mammalian (or mechanistic) target of rapamycin (mTOR) pathway have a major role in proliferation and cell survival in breast cancer. However, as single agents, mTOR inhibitors have had modest antitumor efficacy. In this study, we evaluated the effects of vertical inhibition of mTOR and Akt in breast cancer cell lines and xenografts. We assessed the effects of mTOR inhibitor rapamycin and Akt inhibitor MK-2206, given as single drugs or in combination, on cell signaling, cell proliferation and apoptosis in a panel of cancer cell lines in vitro. The antitumor efficacy was tested in vivo. We demonstrated that MK-2206 inhibited Akt phosphorylation, cell proliferation and apoptosis in a dose-dependent manner in breast cancer cell lines. Rapamycin inhibited S6 phosphorylation and cell proliferation, and resulted in lower levels of apoptosis induction. Furthermore, the combination treatment inhibited phosphorylation of Akt and S6, synergistically inhibited proliferation and induced apoptosis with a higher efficacy. In vivo combination inhibited tumor growth more than either agent alone. Our data suggest that a combination of Akt and mTOR inhibitors have greater antitumor activity in breast cancer cells, which may be a viable approach to treat patients. PMID- 28991259 TI - Impaired p65 degradation by decreased chaperone-mediated autophagy activity facilitates epithelial-to-mesenchymal transition. AB - Aberrant activation of nuclear factor-kappaB (NF-kappaB) has been observed in a wide range of human cancers and is thought to promote tumorigenesis and metastasis. As a central component of NF-kappaB pathway, p65 protein level is tightly regulated and could be subjected to proteasome degradation. Here we demonstrated that p65 can bind to HSC70 with four consensus recognition motif in its RHD domain and be constitutively transported to the lysosome membrane to bind with lysosome-associated membrane protein type 2A and degraded within the lysosome in two epithelial cell lines, proposing that p65 can be degraded by chaperone-mediated autophagy (CMA). Of great importance, there is a decreased CMA activity together with impaired degradation of p65 in a process of epithelial mesenchymal transition (EMT). The resulted accumulation of p65 leads to higher NF kappaB activity and contributes to the progression and maintenance of the EMT program. Taken together, our results define a novel regulatory mechanism for the important transcription factor p65, and these findings would shed new light on the inhibition of EMT, as well as metastasis of cancer cells. PMID- 28991260 TI - Protein and chemotherapy profiling of extracellular vesicles harvested from therapeutic induced senescent triple negative breast cancer cells. AB - Triple negative breast cancer (TNBC) is an aggressive subtype with relatively poor clinical outcomes and limited treatment options. Chemotherapy, while killing cancer cells, can result in the generation of highly chemoresistant therapeutic induced senescent (TIS) cells that potentially form stem cell niches resulting in metastases. Intriguingly, senescent cells release significantly more extracellular vesicles (EVs) than non-senescent cells. Our aim was to profile EVs harvested from TIS TNBC cells compared with control cells to identify a potential mechanism by which TIS TNBC cells maintain survival in the face of chemotherapy. TIS was induced and confirmed in Cal51 TNBC cells using the chemotherapeutic paclitaxel (PTX) (Taxol). Mass spectrometry (MS) analysis of EVs harvested from TIS compared with control Cal51 cells was performed using Ingenuity Pathway Analysis and InnateDB programs. We demonstrate that TIS Cal51 cells treated with 75 nM PTX for 7 days became senescent (senescence-associated beta-galactosidase (SA-beta-Gal) positive, Ki67-negative, increased p21 and p16, G2/M cell cycle arrest) and released significantly more EVs (P=0.0002) and exosomes (P=0.0007) than non-senescent control cells. Moreover, TIS cells displayed an increased expression of the multidrug resistance protein 1/p-glycoprotein. MS analysis demonstrated that EVs derived from senescent Cal51 cells contained 142 proteins with a significant increased fold change compared with control EVs. Key proteins included ATPases, annexins, tubulins, integrins, Rabs and insoluble senescence associated secretory phenotype (SASP) factors. A fluorescent analogue of PTX (Flutax-2) allowed appreciation of the removal of chemotherapy in EVs from senescent cells. Treatment of TIS cells with the exosome biogenesis inhibitor GW4869 resulted in reduced SA-beta-Gal staining (P=0.04). In summary, this study demonstrates that TIS cells release significantly more EVs compared with control cells, containing chemotherapy and key proteins involved in cell proliferation, ATP depletion, apoptosis and the SASP. These findings may partially explain why cancer senescent cells remain viable despite chemotherapeutic challenge. PMID- 28991257 TI - Contribution of rare inherited and de novo variants in 2,871 congenital heart disease probands. AB - Congenital heart disease (CHD) is the leading cause of mortality from birth defects. Here, exome sequencing of a single cohort of 2,871 CHD probands, including 2,645 parent-offspring trios, implicated rare inherited mutations in 1.8%, including a recessive founder mutation in GDF1 accounting for ~5% of severe CHD in Ashkenazim, recessive genotypes in MYH6 accounting for ~11% of Shone complex, and dominant FLT4 mutations accounting for 2.3% of Tetralogy of Fallot. De novo mutations (DNMs) accounted for 8% of cases, including ~3% of isolated CHD patients and ~28% with both neurodevelopmental and extra-cardiac congenital anomalies. Seven genes surpassed thresholds for genome-wide significance, and 12 genes not previously implicated in CHD had >70% probability of being disease related. DNMs in ~440 genes were inferred to contribute to CHD. Striking overlap between genes with damaging DNMs in probands with CHD and autism was also found. PMID- 28991261 TI - ESRP1 is overexpressed in ovarian cancer and promotes switching from mesenchymal to epithelial phenotype in ovarian cancer cells. AB - Epithelial splicing regulatory protein 1 (ESRP1) and 2 (ESRP2), epithelial cell specific regulators of alternative splicing, are downregulated during the epithelial-mesenchymal transition (EMT). These factors have roles in tumor progression and metastasis in some cancers; however, their expression and function in ovarian cancer (OC) remain unclear. We found that ESRP1 and ESRP2 mRNAs were expressed at higher levels in OC cells than in immortalized ovarian surface epithelial (IOSE) cells, and confirmed their overexpression in OC tissues at the protein level. The Cancer Genome Atlas (TCGA) data analysis revealed frequent gene amplification of ESRP1 in OC tissues; however, we detected no significant correlation between ESRP1 gene copy number and gene expression in OC cells. Importantly, expression of ESRP1 and ESRP2 was inversely correlated with DNA methylation in OC cells, and ESRP2 overexpression in OC tissues was significantly associated with DNA hypomethylation. Notably, survival analysis using TCGA data from 541 OC tissues revealed that high ESRP1 expression was significantly associated with shorter 5-year survival of patients. Ectopic ESRP1 expression in mesenchymal OC cells promoted cell proliferation but suppressed cell migration. Furthermore, we found that ESRP1 drives a switch from mesenchymal to epithelial phenotype characterized by reduced cell migration in association with induction of epithelial cell-specific variant of CD44 and ENAH. Taken together, our findings suggest that an epigenetic mechanism is involved in ESRP1 overexpression, and that ESRP1 has a role in OC progression. PMID- 28991263 TI - Structural basis for GABAA receptor potentiation by neurosteroids. AB - Type A gamma-aminobutyric acid receptors (GABAARs) are the principal mediators of inhibitory neurotransmission in the human brain. Endogenous neurosteroids interact with GABAARs to regulate acute and chronic anxiety and are potent sedative, analgesic, anticonvulsant and anesthetic agents. Their mode of binding and mechanism of receptor potentiation, however, remain unknown. Here we report crystal structures of a chimeric GABAAR construct in apo and pregnanolone-bound states. The neurosteroid-binding site is mechanically coupled to the helices lining the ion channel pore and modulates the desensitization-gate conformation. We demonstrate that the equivalent site is responsible for physiological, heteromeric GABAAR potentiation and explain the contrasting modulatory properties of 3a versus 3b neurosteroid epimers. These results illustrate how peripheral lipid ligands can regulate the desensitization gate of GABAARs, a process of broad relevance to pentameric ligand-gated ion channels. PMID- 28991262 TI - NDPKA is not just a metastasis suppressor - be aware of its metastasis-promoting role in neuroblastoma. AB - NDPK-A, encoded by nm23-H1 (also known as NME1) was the first metastasis suppressor discovered. Much of the attention has been focused on the metastasis suppressing role of NDPK-A in human tumors, including breast carcinoma and melanoma. However, compelling evidence points to a metastasis-promoting role of NDPK-A in certain tumors such as neuroblastoma and lymphoma. To balance attention on this contrariety of NDPK-A in different cancer types, this review addresses the metastasis-promoting role of NDPK-A in neuroblastoma. Neuroblastoma is an embryonic tumor, arising from neural crest cells that fail to differentiate into the sympathetic nervous system. We summarize and discuss nm23-H1 genetics and the prognosis of neuroblastoma, structural and functional changes associated with the S120G mutation of NDPK-A, as well as the evidence supporting the role of NDPK-A as a metastasis promoter. Also discussed are the NDPK-A relevant molecular determinants of neuroblastoma metastasis, and metastasis-relevant neural crest development. Because of NDPK-A's dichotomous role in tumor metastasis as both a suppressor and a promoter, tumor genome/exome profiles are necessary to identify the molecular drivers of metastasis in the NDPK-A network for developing tumor specific therapies. PMID- 28991264 TI - Architectural alterations of the fission yeast genome during the cell cycle. AB - Eukaryotic genomes are highly ordered through various mechanisms, including topologically associating domain (TAD) organization. We employed an in situ Hi-C approach to follow the 3D organization of the fission yeast genome during the cell cycle. We demonstrate that during mitosis, large domains of 300 kb-1 Mb are formed by condensin. This mitotic domain organization does not suddenly dissolve, but gradually diminishes until the next mitosis. By contrast, small domains of 30 40 kb that are formed by cohesin are relatively stable across the cell cycle. Condensin and cohesin mediate long- and short-range contacts, respectively, by bridging their binding sites, thereby forming the large and small domains. These domains are inversely regulated during the cell cycle but assemble independently. Our study describes the chromosomal oscillation between the formation and decay phases of the large and small domains, and we predict that the condensin-mediated domains serve as chromosomal compaction units. PMID- 28991265 TI - A structural model for microtubule minus-end recognition and protection by CAMSAP proteins. AB - CAMSAP and Patronin family members regulate microtubule minus-end stability and localization and thus organize noncentrosomal microtubule networks, which are essential for cell division, polarization and differentiation. Here, we found that the CAMSAP C-terminal CKK domain is widely present among eukaryotes and autonomously recognizes microtubule minus ends. Through a combination of structural approaches, we uncovered how mammalian CKK binds between two tubulin dimers at the interprotofilament interface on the outer microtubule surface. In vitro reconstitution assays combined with high-resolution fluorescence microscopy and cryo-electron tomography suggested that CKK preferentially associates with the transition zone between curved protofilaments and the regular microtubule lattice. We propose that minus-end-specific features of the interprotofilament interface at this site serve as the basis for CKK's minus-end preference. The steric clash between microtubule-bound CKK and kinesin motors explains how CKK protects microtubule minus ends against kinesin-13-induced depolymerization and thus controls the stability of free microtubule minus ends. PMID- 28991266 TI - MacroH2A1.1 regulates mitochondrial respiration by limiting nuclear NAD+ consumption. AB - Histone variants are structural components of eukaryotic chromatin that can replace replication-coupled histones in the nucleosome. The histone variant macroH2A1.1 contains a macrodomain capable of binding NAD+-derived metabolites. Here we report that macroH2A1.1 is rapidly induced during myogenic differentiation through a switch in alternative splicing, and that myotubes that lack macroH2A1.1 have a defect in mitochondrial respiratory capacity. We found that the metabolite-binding macrodomain was essential for sustained optimal mitochondrial function but dispensable for gene regulation. Through direct binding, macroH2A1.1 inhibits basal poly-ADP ribose polymerase 1 (PARP-1) activity and thus reduces nuclear NAD+ consumption. The resultant accumulation of the NAD+ precursor NMN allows for maintenance of mitochondrial NAD+ pools that are critical for respiration. Our data indicate that macroH2A1.1-containing chromatin regulates mitochondrial respiration by limiting nuclear NAD+ consumption and establishing a buffer of NAD+ precursors in differentiated cells. PMID- 28991269 TI - Engineered bacteria self-organize to sense pressure. PMID- 28991268 TI - Programmable assembly of pressure sensors using pattern-forming bacteria. AB - Biological systems can generate microstructured materials that combine organic and inorganic components and possess diverse physical and chemical properties. However, these natural processes in materials fabrication are not readily programmable. Here, we use a synthetic-biology approach to assemble patterned materials. We demonstrate programmable fabrication of three-dimensional (3D) materials by printing engineered self-patterning bacteria on permeable membranes that serve as a structural scaffold. Application of gold nanoparticles to the colonies creates hybrid organic-inorganic dome structures. The dynamics of the dome structures' response to pressure is determined by their geometry (colony size, dome height, and pattern), which is easily modified by varying the properties of the membrane (e.g., pore size and hydrophobicity). We generate resettable pressure sensors that process signals in response to varying pressure intensity and duration. PMID- 28991267 TI - Cytotoxic and regulatory roles of mucosal-associated invariant T cells in type 1 diabetes. AB - Type 1 diabetes (T1D) is an autoimmune disease that results from the destruction of pancreatic beta-cells by the immune system that involves innate and adaptive immune cells. Mucosal-associated invariant T cells (MAIT cells) are innate-like T cells that recognize derivatives of precursors of bacterial riboflavin presented by the major histocompatibility complex (MHC) class I-related molecule MR1. Since T1D is associated with modification of the gut microbiota, we investigated MAIT cells in this pathology. In patients with T1D and mice of the non-obese diabetic (NOD) strain, we detected alterations in MAIT cells, including increased production of granzyme B, which occurred before the onset of diabetes. Analysis of NOD mice that were deficient in MR1, and therefore lacked MAIT cells, revealed a loss of gut integrity and increased anti-islet responses associated with exacerbated diabetes. Together our data highlight the role of MAIT cells in the maintenance of gut integrity and the control of anti-islet autoimmune responses. Monitoring of MAIT cells might represent a new biomarker of T1D, while manipulation of these cells might open new therapeutic strategies. PMID- 28991270 TI - How job and family demands impact change in perceived stress: A dyadic study. AB - OBJECTIVES: The aim of this two-wave study has been to test the spillover and crossover of job and family demands on changes in perceived stress at work and in the family. Specifically, we proposed that demands from one domain (work or family) spilled over to another domain through interrrole conflict (work family/family-work conflict) and context-specific self-efficacy. Additionally, we hypothesized that changes in perceived stress were impacted not only by a person's own demands through interrole conflict but also by the demands of one's significant other, in the process of crossover. MATERIAL AND METHODS: The study was of dyadic design and it was conducted online, among 130 heterosexual couples, at 2 time points separated by 3 months interval. Hypotheses were verified by means of the path analysis. RESULTS: No support was found for the spillover of job and family demands on changes in perceived stress through interrole conflict and self-efficacy, neither for women nor for men. With regard to the crossover, no support was found for the actor effects, i.e., a person's demands did not impact changes in one's own work- and family-related perceived stress but partial support was found for the partner effects, i.e., women's job demands were associated with men's changes in work and family-related stress through women's work-family conflict, and men's family demands were associated with women's change in family-related perceived stress through men's family-work conflict. CONCLUSIONS: The study is a longitudinal test of the Spillover-Crossover model and Work-Home Resources model demonstrating that job and family demands are transmitted across domains and across partners in the intimate relationships through the interrole conflict but the nature of this crossover is different for men and women. Int J Occup Med Environ Health 2018;31(2)199-215. PMID- 28991271 TI - Diabetes mellitus and optic atrophy: study of the Wolfram syndrome AB - Background: Wolfram syndrome (WS), also known by the acronym DIDMOAD, is a rare and progresive hereditary disease of autosomal recessive inheritance which minimum ascertainment diagnostic criteria are the occurrence together of diabetes mellitus and optic atrophy before 15 years of age. Objective: To describe the clinical, biochemical and molecular profile of WS in a tertiary care hospital in Mexico. Materials and Methods: We reviewed patients records who fulfill the minimum ascertainment diagnostic criteria of WS presenting between January 1987 and May 2015 in a tertiary care hospital in Mexico. Results: Five patients fulfill the inclusion criteria (three male and two female). Diabetes mellitus was the first manifestation of the syndrome in all of them, with a mean age at diagnosis of 5.8 +/- 2.71 years, while the WS diagnosis was established at a mean age of 15.8 +/- 8.37 years. All the patients had optic atrophy and two of them presented with the complete DIDMOAD spectrum. We found new associations with autoimmune hepatitis and testicular cancer. Conclusions: This study shows the variability of clinical presentation of WS, as well as two new associations. PMID- 28991272 TI - Glycemic index and glycemic load in the Opuntia ficus-indica fruit AB - : There is evidence that support the clinical usage of glycemic index (GI) and glycemic load (GL) in the prevention of chronic disease. Objective: To determine the GI and GL of the Opuntia ficus-indica fruit. Methodology: An analytic, transversal study was made involving 25 healthy volunteers accepted by an informed consent with a normal body mass index, glucose, glycoside hemoglobin, cholesterol and serum triglycerides. The homogeneity of the population was evaluated with anthropometrical and biochemical data using principal component analysis (PCA). The equivalent of 50 g of carbohydrates test food (tuna) and 50 g of dextrose as food standard was provided for the measure of the glucose curve. The GI was determined by calculating the area under the curve by the triangulation method. The CG was reported as the product of IG by carbohydrate loading provided. Results and Conclusions: The IG of the tuna was 48.01 +/- 17.4, classified as low, while the CG was 24.0 +/- 8.7 rated as high. The chemometric analysis by PCA showed that the selection of the normal population for determining the IG, it is important to consider the values of cholesterol and triglycerides. PMID- 28991273 TI - Educational and evaluation strategies in the training of physician specialists AB - Background: Teaching strategies have been defined as procedures, means or resources that teachers used to promote meaningful learning. Aim: Identify teaching strategies and evaluation used by the professor with residents in tertiary hospitals health care. Methods: This is a cross-sectional study conducted with full, associate and assistant professors of various medical specialties. A questionnaire was applied to evaluate the strategies used by professors to teach and evaluate students. Results: We included a sample of 90 professors in 35 medical specialties. The most frequent teaching activities were: organizing students to develop presentations on specific subjects, followed by asking questions on previously reviewed subjects, In terms of the strategies employed, the most frequent "always" option was applied to case analyses. The most frequent methods used for the evaluation of theoretical knowledge were: participation in class, topic presentation and exams. Conclusions: Teaching activities were primarily based on the presentation of specific topics by the residents. The most commonly used educational strategies were clinical case analyses followed by problem-based learning and the use of illustrations. Evaluation of the residents' performance in theory knowledge, hinged on class participation, presentation of assigned topics and exams. PMID- 28991275 TI - Results of the Survey of Academics PMID- 28991274 TI - Psychosocial risks and stress as predictors of burnout in junior doctors performing emergency guards AB - Objective: To study the stress, the psychosocial risks associated to the job and the burnout, in a group of junior doctors working at the emergency ward; and to analyze what of those variables could predict and are better related with burnout. Methods: Cross-sectional study, with a sample of 42 junior doctors which are on duty in the emergency ward of the University Hospital San Cecilio, Granada (Spain). The Spanish adapted version of the Perceived Stress Scale was used to evaluate stress, the Maslach Burnout Inventory (MBI) to evaluate the professional burnout and the adapted and scaled questionnaire for the self-evaluation of psychosocial risks at work (CopSoQ-ISTAS21). Results: 78% of the junior doctors are in the unfavorable or intermediate range for all CopSoQ-ISTAS21 dimensions, being particularly relevant that 90% of them display unfavorable score in psychological demands. In addition, MBI results show that 45% of our population presents high emotional exhaustion simultaneously to high depersonalization. ISTAS21 psychological demands dimensions (beta = 0.393; p < 0.003) and stress scores (beta = 0.451; p < 0.001) significantly predict emotional exhaustion (r2 = 0.443). Finally, 38% of junior doctors experienced a threat/aggression during their work in the emergency ward urgencies. Conclusion: Junior doctors develop its professional activity under adverse circumstances probably due to the high psychosocial risk associated to the job. Psychological demands are suggested as the main predicting factor of burnout. These results indicate the need of psychological and structural interventions in order to improve the professional performance of junior doctors at the emergency ward. PMID- 28991276 TI - Medical residency in Germany: an open option for Mexican physicians PMID- 28991277 TI - Liver transplantation center in Mexico with low-volume and excellent results AB - Background: Orthotopic liver transplantation (OLT) is the treatment of choice for end stage liver disease. Many studies show an inverse relationship between the number of procedures and operative mortality. Objective: The objective of the study is to show the results of our center and determine if it can have comparable results to high volumen centers. Method: This is a retrospective study which analyzed the information of patients with OLT at our institution from 1985 to December 31, 2012. Depending on date of transplantation, the study was divided into three stages. Stage 1: from 1985 to 1999. Stage 2: from 2000 to 2007. Stage 3: from 2008 to 2012. In the 1, 2 and 3 stage 22, 37 and 56 OLT were performed respectively. Results: Perioperative mortality was significantly lower between Stage 3 vs. Stage 1 and 2 (3.5% vs. 50% and 21.7%, p = 0.001). Patient survival was also better at 1 and 5 years at Stage 3 (94.4%, 87.8%) vs. era 2 (77.6%, 66.17%) and Stage 1 (47% and 29%) (p = 0.001). Conclusion: In conclusion, the present results of OLT at our program are excellent despite being a low-volume center. PMID- 28991278 TI - Thrombophilia in Mexico PMID- 28991279 TI - The role of gamma-aminobutyric acid in female depression AB - Depression is a common psychiatric disorder and a leading cause of disability worldwide. Multiple and diverse factors are involved in its cause although biologic factors are prominent. The present study reviews the evidence about the role that gamma-aminobutyric acid plays in the complex pathogenesis of depression, particularly in women. The implication of gamma-aminobutyric acid (GABA) is based mainly from animal models whereas clinical studies in depressed patients show alterations of GABA levels in plasma and cerebrospinal fluid. Neuroimaging studies using spectroscopy indicate also decreased GABA levels in different brain areas which in turn may normalize after antidepressant therapy, and these findings translate into clinical response. It has been observed that depression has a higher prevalence among women which suggests a link between depression and hormonal changes. Similarly, gonadal hormones have a regulatory effect on the hypothalamic-pituitary-adrenal axis through GABA receptors making women more vulnerable to suffer stress and depression. Therefore, the implication of GABA in the neurobiology of depression should be explored in order to search for new therapeutic strategies. PMID- 28991281 TI - Splanchnic vein thrombosis as a first manifestation of Primary myelofibrosis AB - Myeloproliferative neoplasms are chronic disorders of clonal hematopoietic stem cells, characterized by an overproduction of functional granulocytes, red blood cells and / or platelets, and one of the major complications is the occurrence of venous and arterial thrombotic problems caused by increased platelet aggregation and thrombin generation. In this study 11 cases of primary myelofibrosis (PM) were evaluated and 2 debuted with splanchnic venous thrombosis (SVT); so after seeing the results of this study and of world literature, it is suggested that in patients with SVT, diagnostic methods for PM like the JAK2V617F mutation should be included. PMID- 28991280 TI - Platelet-rich plasma and its effect in bone regeneration in mandibular fractures. Controlled clinical trial AB - Background: Currently there is great interest in developing clinical applications of platelet-rich plasma to enhance bone repair. Aim: To assess bone regeneration in mandibular fractures, with the application of this adjuvant. Methods: Twenty patients with mandibular fractures were included in a randomized clinical trial. Patients of the experimental group (n = 10) were submitted to internal fracture reduction and administration of platelet-rich plasma, and patients of the control group (n = 10) were submitted to the same surgical procedure without plasma application. Radiologic assessment was made before and at 1 and 3 months after surgery. X-rays were digitalized for analyze intensity and density as reflection of bone regeneration. Results: The average age was 32 +/- 11.3 years and 31.2 +/- 8.48 years respectively (p = 0.76). The radiographic intensity and density in the experimental group at the 1st and 3rd month were higher in contrast to the control group (p < 0.005). Bone regeneration time was 3.7 +/- 0.48 and 4.5 +/- 0.52 weeks respectively (p = 0.002). There was no morbidity related to the application of the platelet-rich plasma. Conclusion: The platelet-rich plasma increased the bone intensity and density in the fracture trace allowing bone regeneration and recovery in shorter time than patients in which it was not used. PMID- 28991283 TI - Death and bioetics in the intensive care unit PMID- 28991282 TI - Knowledge and attitude towards organ donation of medicine students of a Northwestern Mexico public university AB - Objective: To evaluate the knowledge and attitude towards organ donation of medicine students of a Northwestern Mexico public university. Materials and Methods: A prolective, descriptive, observational, and cross-sectional study. A 34 items cross-sectional survey evaluating knowledge and attitude towards organ donation in 3,056 medicine students during 2013-2015. Descriptive statistics were used as absolute frequencies, percentages, mean and standard deviation, as well as the Chi-square test. A p < 0.05 was considered significant. Results: 74% of students would donate their own organs, mainly due to reciprocity (41%). 26% of students would not donate, 48% of them because of fear that their organs could be taken before death. 86% would donate organs from a relative. 64% have spoken about organ donation and transplantation with their family and 67% with friends. 50% said they had received no information about it. 68% understand the concept of brain death. Conclusion: Students received little information about organ donation during college. Despite that, most of them showed a positive attitude and are willing to donate. PMID- 28991284 TI - Thrombophilia PMID- 28991285 TI - Influenza 2009: experience, lessons and pendings PMID- 28991286 TI - The need to publish and the birth of medical predatory magazines PMID- 28991287 TI - News in periodical medical publications. The case of free journals (Open Journals) PMID- 28991288 TI - Psoriasis and diabetes mellitus in the dermatological consultation. PMID- 28991289 TI - Physical activity and its association with chronic diseases in the elderly in 11 cities of Peru AB - Aim: To determine the frequency of physical activity and its association with chronic diseases in the elderly in eleven cities of Peru. Methods: A cross sectional study of secondary data was conducted; the dependent variable was not the realization of physical activity, chronic disease and other physio anthropometric variables were independent variables. For bivariate and multivariate analysis generalized linear models were used. A confidence level of 95% and p < 0.05 as statistically significant was considered. Results: Of the 1030 elderly 68% (698) did not perform physical activity. When performing the multivariate model was obtained for every year of age increased by 1.5% frequency do physical activity (RPA: 1.015, 95% CI 1.006-1.024, p = 0.001) for each additional centimeter waist decreased 0.6% performing physical activity (RPA: 0.994, 95% CI: 0.992-0.997, p < 0.001) and those suffering from other chronic heart disease (RPA: 1.15, 95% CI: 1.02-1.30. p = 0.019) had higher frequencies of no physical activity, adjusted for sex and city of residence. Conclusion: No physical activity was associated with suffering from some heart disease, older age and waist circumference. We need to consider these results from the study to promote physical activity in this population. PMID- 28991290 TI - Primary thrombosis of the anterior descending in a patient with antiphospholipid antibody syndrome AB - Antiphospholipid antibody syndrome is a heterogeneous clinical and biochemical entity. We present the case of a young male with history of venous thromboembolism. This time he presents because of chest ischemic pain associated with ST segment elevation. He was taken to the cath lab to perform a primary percutaneous coronary intervention and a total occlusion of the left anterior descending artery was noted. Successful thrombus aspiration was performed. No stent was deployed. He was taken to the cath lab for a second look angiography and no atherosclerotic lesions were observed, which was confirmed by intravascular ultrasound. PMID- 28991291 TI - Catastrophic antiphospholipid syndrome. Case report and literature review AB - The present document is the report of a case of a very rare clinical entity, which presents with acute multiorganic failure after a thrombotic storm related to antiphospholipid antibodies, the so-called catastrophic antiphospholipid syndrome, which began as a recurrent picture of mesenteric thrombosis, with a previous history of venous insufficiency and distal ulcers probably associated with an unidentified antiphospholipid; deserving management in intensive care and the consultation by the world expert, Dr. Ricard Cervera who confirmed the diagnosis and recommend treating as such entity, the patient's evolution was satisfactory so far. Final recommendations for diagnosis and current treatment options such as rituximab or eculizumab are made. The present case was added to the international registry that currently houses around 500 cases worldwide (International CAPS Registry). PMID- 28991292 TI - Neutron diffraction and gravimetric study of the iron nitriding reaction under ammonia decomposition conditions. AB - Ammonia decomposition over iron catalysts is known to be affected by whether the iron exists in elemental form or as a nitride. In situ neutron diffraction studies with simultaneous gravimetric analysis were performed on the nitriding and denitriding reactions of iron under ammonia decomposition conditions. The gravimetric analysis agrees well with the Rietveld analysis of the neutron diffraction data, both of which confirm that the form of the iron catalyst is strongly dependent on ammonia decomposition conditions. Use of ammonia with natural isotopic abundance as the nitriding agent means that the incoherent neutron scattering of any hydrogen within the gases present is able to be correlated to how much ammonia had decomposed. This novel analysis reveals that the nitriding of the iron occurred at exactly the same temperature as ammonia decomposition started. The iron nitriding and denitriding reactions are shown to be related to steps that take place during ammonia decomposition and the optimum conditions for ammonia decomposition over iron catalysts are discussed. PMID- 28991293 TI - Alkene-assisted cis-to-trans isomerization of non-conjugated polyunsaturated alkenes. AB - Complex [Cp*Ru(NCMe)3][PF6], 1a, has been identified as a cis-to-trans isomerization catalyst of various non-conjugated cis-polyalkenes under exceptional kinetic control as no alkene conjugation was observed. According to the experimental and theoretical data, the cis-trans isomerization occurred via an alkene-assisted mechanism in which one cis-double bond always served as an anchoring site. Using a combination of multinuclear NMR spectroscopic evidence and mathematical methods it was possible to determine the extent of trans isomerization. PMID- 28991295 TI - Isomerization of methoxy radical in the troposphere: competition between acidic, neutral and basic catalysts. AB - A comprehensive investigation of the roles of acidic, neutral and basic catalysts in isomerization of methoxy radical in the troposphere has been carried out by quantum chemical calculations at the MP2 and CCSD(T) levels of theory. The effect of basic catalysts, namely ammonia and an ammonia-water complex, on the isomerization process has been studied for the very first time. In terms of rate coefficients ammonia was found to be a better catalyst than a water monomer whereas the ammonia-water complex was found to be more efficient over a water dimer but marginally less efficient than formic acid. Based on the effective rate constants under various tropospheric conditions, it was found that at 0 km altitude water dimers and ammonia-water complexes could compete with acid catalysts but at higher altitudes the acid catalysts would dominate their neutral and basic counterparts by a long distance. PMID- 28991294 TI - Multifaceted peptide assisted one-pot synthesis of gold nanoparticles for plectin 1 targeted gemcitabine delivery in pancreatic cancer. AB - An astute modification of the plectin-1-targeting peptide KTLLPTP by introducing a C-terminal cysteine preceded by a tyrosine residue imparted a reducing property to the peptide. This novel property is then exploited to fabricate gold nanoparticles (GNP) via an in situ reduction of gold(iii) chloride in a one-pot, green synthesis. The modified peptide KTLLPTPYC also acts as a template to generate highly monodispersed, spherical GNPs with a narrow size distribution and improved stability. Plectin-1 is known to be aberrantly expressed in the surface of pancreatic ductal adenocarcinoma (PDAC) cells while showing cytoplasmic expression in normal cells. The synthesized GNPs are thus in situ surface modified with the peptides via the cysteine residue leaving the N-terminal KTLLPTP sequence free for targeting plectin-1. The visual molecular dynamics based simulations support the experimental observations like particle size, gemcitabine conjugation and architecture of the peptide-grafted nanoassembly. Additionally, GNPs conjugated to gemcitabine demonstrate significantly higher cytotoxicity in vitro in two established PDAC cell lines (AsPC-1 and PANC-1) and an admirable in vivo antitumor efficacy in a PANC-1 orthotopic xenograft model through selective uptake in PDAC tumor tissues. Altogether, this strategy represents a unique method for the fabrication of a GNP based targeted drug delivery platform using a multifaceted peptide that acts as reducing agent, template for GNP synthesis and targeting agent to display remarkable selectivity towards PDAC. PMID- 28991296 TI - Synthesis of ultra - stable copper nanoclusters and their potential application as a reversible thermometer. AB - A new strategy for the synthesis of luminescent copper nanoclusters (Cu NCs), by virtue of the reduction of Cu2+ using ascorbic acid and the protection of polyvinylpyrrolidone at 75 degrees C, was reported. Blue emitting Cu NCs with photoluminescence (PL) quantum yield of 12% and high stability up to at least 1 month were obtained. Moreover, the PL of Cu NCs showed a reversible response to temperature, and a linear relationship between PL intensity and temperature even after 10 cycles of repeated heating and cooling process was obtained, indicating great potential application in thermal sensors. PMID- 28991297 TI - On-chip polyelectrolyte coating onto magnetic droplets - towards continuous flow assembly of drug delivery capsules. AB - Polyelectrolyte (PE) microcapsules for drug delivery are typically fabricated via layer-by-layer (LbL) deposition of PE layers of alternating charge on sacrificial template microparticles, which usually requires multiple incubation and washing steps that render the process repetitive and time-consuming. Here, ferrofluid droplets were explored for this purpose as an elegant alternative of templates that can be easily manipulated via an external magnetic field, and require only a simple microfluidic chip design and setup. Glass microfluidic devices featuring T junctions or flow focusing junctions for the generation of oil-based ferrofluid droplets in an aqueous continuous phase were investigated. Droplet size was controlled by the microfluidic channel dimensions as well as the flow rates of the ferrofluid and aqueous phases. The generated droplets were stabilised by a surface active polymer, polyvinylpyrrolidone (PVP), and then guided into a chamber featuring alternating, co-laminar PE solutions and wash streams, and deflected across them by means of an external permanent magnet. The extent of droplet deflection was tailored by the flow rates, the concentration of magnetic nanoparticles in the droplets, and the magnetic field strength. PVP-coated ferrofluid droplets were deflected through solutions of polyelectrolyte and washing streams using several iterations of multilaminar flow designs. This culminated in an innovative "Snakes-and-Ladders" inspired microfluidic chip design that overcame various issues of the previous iterations for the deposition of layers of anionic poly(sodium-4-styrene sulfonate) (PSS) and cationic poly(fluorescein isothiocyanate allylamine hydrochloride) (PAH-FITC) onto the droplets. The presented method demonstrates a simple and rapid process for PE layer deposition in <30 seconds, and opens the way towards rapid layer-by-layer assembly of PE microcapsules for drug delivery applications. PMID- 28991298 TI - Exosomal delivery of berry anthocyanidins for the management of ovarian cancer. AB - Despite optimal diagnosis and early therapeutic interventions, the prognosis for ovarian cancer patients remains dismal because the efficacy of chemotherapy is limited by the development of resistance and off-site toxicity. Berry bioactives indicate preventive and therapeutic activities against various cancer types. Here, we examined the antiproliferative activity of berry anthocyanidins (Anthos) against drug-sensitive (A2780) and drug-resistant (A2780/CP70, OVCA432 and OVCA433) ovarian cancer cells. These drug-resistant ovarian cancer cell lines overexpress p-glycoproteins (PgP) and show >100-fold resistance to the chemotherapeutic drug cisplatin compared to A2780. We observed a dose-dependent growth inhibition of ovarian cancer cells with the Anthos. Furthermore, the treatment of drug-resistant ovarian cancer (OVCA433) cells with cisplatin in combination with the Anthos (75 MUM) resulted in significantly higher cell killing. The cisplatin dose required to achieve this effect was 10 to 15-fold lower than the IC50 of cisplatin alone. However, many plant bioactives including Anthos face the challenge of poor oral bioavailability and stability. Recently, we have developed strategies to overcome these limitations by delivering Anthos via milk-derived exosomes. The exosomal Anthos (ExoAnthos) significantly enhanced the antiproliferative activity against the growth of ovarian cancer cells and inhibited tumor growth more efficiently compared to Anthos alone and a vehicle control. Often patients with cisplatin-resistant tumors retain sensitivity to paclitaxel (PAC). We prepared exosomal formulations of PAC (ExoPAC) for oral delivery as the systemic administration of PAC has severe side effects. ExoPAC delivered orally showed the same therapeutic efficacy as the free PAC delivered intraperitoneally. Finally, we report that the combination of the Anthos and PAC decreased the PgP level in a dose-dependent manner in OVCA432 cells. A significantly enhanced antitumor activity was observed with the combination of ExoPAC and ExoAnthos against A2780 tumor xenografts. Together, our data indicate that the berry Anthos are highly effective against ovarian cancer and that the milk exosomes serve as an excellent nano-carrier to enhance the drug's oral bioavailability for the management of ovarian cancer. PMID- 28991299 TI - Amidine functionalized phosphines: tuneable ligands for transition metals. AB - Attachment of racemic 1,3,5,7-tetramethyl-2,4,6-trioxa-8 phosphatricyclo[3.3.1.13,7]decane (alpha,beta-CgP) to (1R,5S)-1,8,8-trimethyl-2,4 diazabicyclo[3.2.1]oct-2-ene gave a diastereomeric mixture of a novel amidine phosphine ligand, alpha,beta-CgPAm. The phosphination was completely selective for the 4-position of the bicyclic amidine and there was no subsequent 1,2 migration of the alpha,beta-CgP group. Methylation of the non-phosphinated nitrogen gave the amidinium salt [alpha,beta-CgPAmMe]BF4 as a diastereomeric mixture. The donating ability of alpha,beta-CgPAm and [alpha,beta-CgPAmMe]+ has been assessed through the synthesis and characterization of appropriate Rh(i), Au(i) and Pt(ii) complexes. As expected alpha,beta-CgPAm is a better net donor than the cationic derivative as shown by the magnitude of the nuCO stretches in the IR spectra of the [Rh(L)(CO)(acac)]0/+ complexes and through determination of the relative energies of the HOMO and LUMO orbitals for both ligands by DFT. Attempts to resolve [Au(alpha,beta-CgPAmMe)Cl]BF4, [Pt(alpha,beta-CgPAmMe)Cl3], [Rh(alpha,beta-CgPAmMe)(acac)(CO)]BF4 and [Rh(alpha,beta-CgPAmH)(acac)(CO)]BF4 by fractional crystallization were unsuccessful as diastereomeric mixtures were obtained in every case; the structures of the last three complexes have been determined by single-crystal X-ray techniques and compared with related literature complexes. PMID- 28991300 TI - Crystal structure of a DNA duplex containing four Ag(i) ions in consecutive dinuclear Ag(i)-mediated base pairs: 4-thiothymine-2Ag(i)-4-thiothymine. AB - Herein, we determined a high-resolution crystal structure of a B-form DNA duplex containing consecutive dinuclear metal ion-mediated base pairs, namely, 4 thiothymine-2Ag(i)-4-thiothymine (S-2Ag(i)-S), and four Ag(i) ions form a rectangular network and the distances between the Ag(i) ions are 2.8-3.2 A, which may indicate the existence of metallophilic attractions. PMID- 28991301 TI - Mathematical models of cytotoxic effects in endpoint tumor cell line assays: critical assessment of the application of a single parametric value as a standard criterion to quantify the dose-response effects and new unexplored proposal formats. AB - The development of convenient tools for describing and quantifying the effects of standard and novel therapeutic agents is essential for the research community, to perform more precise evaluations. Although mathematical models and quantification criteria have been exchanged in the last decade between different fields of study, there are relevant methodologies that lack proper mathematical descriptions and standard criteria to quantify their responses. Therefore, part of the relevant information that can be drawn from the experimental results obtained and the quantification of its statistical reliability are lost. Despite its relevance, there is not a standard form for the in vitro endpoint tumor cell lines' assays (TCLA) that enables the evaluation of the cytotoxic dose-response effects of anti-tumor drugs. The analysis of all the specific problems associated with the diverse nature of the available TCLA used is unfeasible. However, since most TCLA share the main objectives and similar operative requirements, we have chosen the sulforhodamine B (SRB) colorimetric assay for cytotoxicity screening of tumor cell lines as an experimental case study. In this work, the common biological and practical non-linear dose-response mathematical models are tested against experimental data and, following several statistical analyses, the model based on the Weibull distribution was confirmed as the convenient approximation to test the cytotoxic effectiveness of anti-tumor compounds. Then, the advantages and disadvantages of all the different parametric criteria derived from the model, which enable the quantification of the dose-response drug-effects, are extensively discussed. Therefore, model and standard criteria for easily performing the comparisons between different compounds are established. The advantages include a simple application, provision of parametric estimations that characterize the response as standard criteria, economization of experimental effort and enabling rigorous comparisons among the effects of different compounds and experimental approaches. In all experimental data fitted, the calculated parameters were always statistically significant, the equations proved to be consistent and the correlation coefficient of determination was, in most of the cases, higher than 0.98. PMID- 28991302 TI - The preparation and electrorheological behavior of bowl-like titanium oxide nanoparticles. AB - Bowl-like titanium oxide nanoparticles were successfully prepared by a simple solvothermal method using absolute ethanol and isopropanol as the cosolvent. Ostwald ripening coupled with the inner-stress-induce effect were assumed to play an important role in the formation of this unique bowl-like morphology. The morphological evolution from solid nanosphere to bowl-like nanoparticle was investigated by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Besides, the structural characteristics of the as-synthesized TiO2 nanoparticles were confirmed by X-ray diffraction (XRD), Fourier transform infrared (FT-IR) and thermogravimetric analysis (TGA). Moreover, a rotational rheometer was operated to examine the electrorheological (ER) effect. Excellent ER properties were achieved when the TiO2 particles were dispersed in silicone oil under an external electric field. PMID- 28991303 TI - In situ hybridization of enzymes and their metal-organic framework analogues with enhanced activity and stability by biomimetic mineralisation. AB - By incorporating Cytochrome c (peroxidase, Cyt c) into a skeleton of its corresponding synthetic MOF analogue (peroxidase mimic, CuBDC), approximately 12 fold catalytic efficiency (kcat/KM) enhancement is observed compared to free Cyt c. Meanwhile, the shield endowed by CuBDC prevents encapsulated enzymes from deactivation by trypsin digestion, thermal treatment and long-term storage in vitro. This concept of combining enzymes and their MOF mimics with enhanced enzymatic activity and stability may provide new insights into the design of highly active, stable enzyme-MOF composite catalysts and holds promise for applications in biocatalysis, biosensing and drug delivery systems. PMID- 28991304 TI - Lamellar structures in fluorinated phosphonium ionic liquids: the roles of fluorination and chain length. AB - Ionic liquids (ILs) exhibit tunable behaviour and properties that are due to their supramolecular structure. We synthesized a series of alkylated and fluorinated phosphonium dicyanamide ILs to study the relation between molecular structure and assembly with a focus on the roles of cation chain length and fluorination. Small angle X-ray scattering indicated a lamellar structure with long-range order for all fluorinated ILs, while alkylated ILs showed only the general structures of ILs, i.e., alternating a polar ionic-zone and a nonpolar alkyl-zone. "Fluorophobic" interactions caused microphase segregation between perfluorinated and other molecular segments, "fluorophilic" interactions among the perfluorinated segments stabilized the microphase structure, and the coupling of "fluorophobic" and "fluorophilic" interactions resulted in a stable mesophase structure. The perfluorinated segments packed more densely than the alkylated analogues; the fluorinated versions (except for F2) liquefied at temperatures considerably above that of alkylated ILs. The lamellar structures strongly affected the rheology of the ILs. Fluorinated ILs had higher viscosities and exhibited non-Newtonian shear thinning; the alkylated ILs of the same length had an order of magnitude lower viscosities and were purely Newtonian. We propose that the disruption of lamellar structure in the shear flow causes the non Newtonian flow behaviour. PMID- 28991305 TI - A modified molecular framework derived highly efficient Mn-Co-carbon cathode for a flexible Zn-air battery. AB - A controllable Co doping strategy is introduced to significantly activate more catalytic sites for Mn-based materials and anchor Co-Mn nanoparticles on the N doped carbon nanotube (N-CNT) substrates. The as-synthesized CoMn2O4/N-CNTs exhibit excellent ORR catalytic performance with large limited current density and positive half-wave potential, even outperforming the Pt/C catalysts. The outstanding ORR activity allows the CoMn2O4/N-CNTs to directly serve as the cathode electrode in a liquid/solid state Zn-air battery, demonstrating large power density and robust stability. PMID- 28991306 TI - Recent progress in layered double hydroxide based materials for electrochemical capacitors: design, synthesis and performance. AB - As representative two-dimensional (2D) materials, layered double hydroxides (LDHs) have received increasing attention in electrochemical energy storage and conversion because of the facile tunability between their composition and morphology. The high dispersion of active species in layered arrays, the simple exfoliation into monolayer nanosheets and chemical modification offer the LDHs an opportunity as active electrode materials in electrochemical capacitors (ECs). LDHs are favourable in providing large specific surface areas, good transport features as well as attractive physicochemical properties. In this review, our purpose is to provide a detailed summary of recent developments in the synthesis and electrochemical performance of the LDHs. Their composites with carbon (carbon quantum dots, carbon black, carbon nanotubes/nanofibers, graphene/graphene oxides), metals (nickel, platinum, silver), metal oxides (TiO2, Co3O4, CuO, MnO2, Fe3O4), metal sulfides/phosphides (CoS, NiCo2S4, NiP), MOFs (MOF derivatives) and polymers (PEDOT:PSS, PPy (polypyrrole), P(NIPAM-co-SPMA) and PET) are also discussed in this review. The relationship between structures and electrochemical properties as well as the associated charge-storage mechanisms is discussed. Moreover, challenges and prospects of the LDHs for high-performance ECs are presented. This review sheds light on the sustainable development of ECs with LDH based electrode materials. PMID- 28991307 TI - An enzyme free electrochemical biosensor for sensitive detection of miRNA with a high discrimination factor by coupling the strand displacement reaction and catalytic hairpin assembly recycling. AB - An isothermal, enzyme free, ultra-specific and ultra-sensitive protocol for electrochemical detection of miRNAs is proposed based on the toehold-mediated strand displacement reaction (SDR) and non-enzymatic catalytic hairpin reaction (CHA) recycling. The SDR was first triggered only in the presence of target miRNA and this process also affects other miRNA interferences having similar target sequences, thus guaranteeing a high discrimination factor and could be used in rare content miRNA detection with various amounts of interferences having similar target sequences. The output protector strand then triggered enzyme free CHA amplification and generates plenty of hairpin self-assembly products. This process in turn influences SDR equilibrium to move to the right and generates large amounts of protector output to ensure analysis sensitivity. Compared with traditional CHA, our proposed method greatly improved the signal to noise ratio and shows excellent performance in rare miRNA detection with miRNA analogue interference. Under the optimal experimental conditions and using square wave voltammetry, the established biosensor could detect target miRNA-21 down to 30 fM (S/N = 3) with a dynamic range from 100 fM to 2 nM, and discriminate rare target miRNA-21 from mismatched miRNA with high selectivity. This method holds great promise in miRNA detection from human cancer cell lines and would be a versatile and powerful tool for clinical molecular diagnostics. PMID- 28991308 TI - Theory of the thermodynamic influence of solution-phase additives in shape controlled nanocrystal synthesis. AB - Though many experimental studies have documented that certain solution-phase additives can play a key role in the shape-selective synthesis of metal nanocrystals, the origins and mechanisms of this shape selectivity are still unclear. One possible role of such molecules is to thermodynamically induce the equilibrium shape of a nanocrystal by altering the interfacial free energies of the facets. Using a multi-scheme thermodynamic integration method that we recently developed [J. Chem. Phys., 2016, 145, 194108], we calculate the solid liquid interfacial free energies gammasl and investigate the propensity to achieve equilibrium shapes in such syntheses. We first apply this method to Ag(100) and Ag(111) facets in ethylene glycol solution containing polyvinylpyrrolidone (PVP), to mimic the environment in polyol synthesis of Ag nanocrystals. We find that although PVP has a preferred binding to Ag(100), its selectivity is not sufficient to induce a thermodynamic preference for {100} faceted nanocubes, as has been observed experimentally. This indicates that PVP promotes Ag nanocube formation kinetically rather than thermodynamically. We further quantify the thermodynamic influence of adsorbed solution-phase additives for generic molecules, by building a gammasl ratio/nanocrystal shape map as a function of zero-temperature binding energies. This map can be used to gauge the efficacy of candidate additive molecules for producing targeted thermodynamic nanocrystal shapes. The results indicate that only additives with a strong facet selectivity can impart significant thermodynamic-shape change. Therefore, many of the nanocrystals observed in experiments are likely kinetic products. PMID- 28991309 TI - Unprecedented 22,26-seco physalins from Physalis angulata and their anti inflammatory potential. AB - Two novel physalins, including a 22,26-seco physalin, physalin X (1), and a 11,15 cyclo-9(10),14(17),22(26)-triseco physalin with an unprecedented aromatic ring, aromaphysalin B (2), were isolated from Physalis angulata L. Their structures were determined by IR, UV, HRESIMS, and 2D NMR spectra as well as theoretical calculations. Compounds 1 and 2 exhibited inhibitory activities on NO production with IC50 values of 68.50 and 29.69 MUM, respectively. A plausible biosynthetic pathway for 2 is also discussed. PMID- 28991310 TI - A highly selective fluorescence turn-on detection of ClO- with 1-methyl-1,2 dihydropyridine-2-thione unit modified tetraphenylethylene. AB - A new selective and sensitive fluorescence turn-on detection of ClO- is reported by taking advantage of the specific reaction between a 1-methyl-1,2 dihydropyridine-2-thione unit and ClO- and the aggregation induced-emission (AIE) behavior of the tetraphenylethylene unit. PMID- 28991311 TI - Selenium fortification of infant formulas: does selenium form matter? AB - Selenium is a trace element essential for the health and development of the growing infant. It is a necessary component of proteins and enzymes required for a variety of functions, including antioxidant defense, modulation of the inflammatory response, and production of thyroid hormones. In breast-fed infants, selenium stores depend on the selenium content of the mother's diet. In formula fed infants, selenium levels are correlated to the residual selenium stores accumulated in utero and the level and type of selenium fortification used in the formula. Today, the United States Food and Drug Administration (FDA) recommends that infant formulas contain selenium at levels between 2.0 and 7.0 MUg per 100 kcal. While the US FDA does not recommend a particular selenium form for fortification, evidence indicates that organically bound selenium forms (e.g., selenomethionine and selenium-enriched yeast) are better absorbed and retained than inorganic forms (e.g., selenite and selenate). Preliminary data from studies in adults do suggest that fortification with standardized selenium-enriched yeast may offer benefits compared to fortification with other organically bound selenium forms. However, because most studies evaluating the impact of selenium fortification of infant formula have assessed inorganic selenium supplements, additional research into the bioavailability and outcomes associated with the use of selenium-enriched yeast in infants is needed. PMID- 28991312 TI - I2/CHP mediated [1 + 1 + 1 + 1] cyclization of aromatic isocyanides with amines to construct 1,3-diazetidine-2,4-diimine derivatives. AB - An I2/CHP (cumene hydroperoxide) mediated [1 + 1 + 1 + 1] cyclization of aromatic isocyanides with readily accessible amines via the formation 4 new C-N bonds has been developed to construct unsymmetric 1,3-diazetidine-2,4-diimine derivatives under mild conditions. PMID- 28991313 TI - Influence of lipid composition of model membranes on methacrylate antimicrobial polymer-membrane interactions. AB - Using atomistic molecular dynamics simulations, the role of lipid composition in the interactions of multiple methacrylate antimicrobial polymer agents with model membranes, and the consequent response of the membranes is studied. In our earlier study, methacrylate polymers were observed to induce phase demixing and associated thickness mismatch in a POPE-POPG model microbial membrane. In this work, we probe (1) the role of varying the degree of saturation in lipid acyl chains in the membrane interactions of methacrylate polymers, and (2) whether electrostatics (addition of anionic lipids) can influence the interactions of the polymers with model mammalian membranes. Lipid composition is observed to significantly modify membrane-polymer interactions, leading to differences in both the mode of partitioning and the conformations adopted by the polymers, in addition to impacting membrane properties differently. The results strongly suggest that the oft-cited electrostatic interactions between the antimicrobial agents and the microbial membranes do not fully account for the recognition and subsequent partitioning of the antimicrobial agents. The ability of the methacrylate polymers to sense interfacial lipid packing defects, determined by the PE/PC head groups of lipids, is also found to be influential in their membrane partitioning. Deliberate inclusion of charged anionic lipids into a model mammalian membrane, leading to additional favorable electrostatics, does not reproduce a similar polymer partitioning mechanism to that in its microbial counterpart. The differences observed in the interactions of methacrylate polymers with the various model membranes can be instrumental in extending our understanding of underlying modes of membrane disruption by general antimicrobial agents as well. PMID- 28991314 TI - Asymmetric synthesis of dihydrocoumarins via the organocatalytic hetero-Diels Alder reaction of ortho-quinone methides. AB - Enantioselective organocatalytic inverse-electron-demand hetero-Diels-Alder reactions of in situ generated ortho-quinone methides with azlactones have been developed. This strategy could generate various chiral dihydrocoumarins bearing a quaternary amino acid moiety in high yields (up to 94%) and stereoselectivities (up to 99 : 1 e.r., >20 : 1 dr) in the presence of a chiral phosphoric acid catalyst. The useful transformation and mechanistic study of this process are also presented. PMID- 28991315 TI - [Impact of rational use of antibiotics in a third level clinic in Colombia]. AB - BACKGROUND: The increasing resistance of bacteria to antibiotics threatens the survival of patients and health costs. AIM: To determine the impact of an antimicrobial stewardship program in bacterial resistance and antibiotic consumption. MATERIALS AND METHODS: Quasi experimental study in a third level clinic in the city of Medellin, that evaluate in two time periods (pre intervention between October 2012 and September 2013 and post intervention between October 2013 and September 2014) the impact of an antimicrobial stewardship program in terms of antibiotic consumption and bacterial ecology. RESULTS: Adherence to institutional guidelines for management of infections in the post-intervention period was 82%. Antibiotic consumption of meropenem, ceftriaxone, vancomycin and colistin decreased, and imipenem, daptomycin and linezolid was increased. A significant decrease in antibiotic resistance in Pseudomonas aeruginosa was observed, including carbapenems. An increase of extended spectrum beta lactamase production (ESBL) in Enterobacteriaceae (especially E. coli) and piperacillin/tazobactam resistance was observed. CONCLUSIONS: The construction and implementation of a strategy in hospitals with guidelines for managing infectious diseases, restrictions in antibiotic use, a permanent monitoring system for the formulation of antibiotics, achieved a positive impact on reducing antibiotic use and bacterial resistance. PMID- 28991316 TI - [Epidemiological characterization of bites on people, as emergency care record: Province of Los Andes, Chile]. AB - BACKGROUND: Bites constitute a public health problem worldwide. AIM: To characterize epidemiologically bites by animals happened in the province of Los Andes (2005-2007). METHOD: Descriptive, retrospective epidemiological study. Studied variables: Bitten person (BP), accident by bite, biting animal and bite. It was not feasible to obtain more updated information by law of patient protection. RESULTS: 2,360 BP were assisted in the emergency unit of San Juan de Dios Hospital and Rio Blanco clinic. An annual average rate of 729 BP/100,000 inhabitants and 1.99 daily average was recorded. The male gender was most affected (53.5%) and the age group from 6 to 10 years old. (Rate: .521/100,000). Most frequent topographic location was the lower limb, except in children under 5 year olds in whom predominated head and neck. The biting animal according to frequency was: the dog (67.1%) spider (7.1%) and cat (3.9%). The animal property was 35.6% known and 30.7% own. The most frequent problems were: nonspecific allergy; toxic effect by spider bites and among the infections, the disease made by cat?s scratch stands out. Regarding the record system, the biting animal complaint was applied to 47.6% of the BP and the 92.8% of the recorded information was incomplete. CONCLUSIONS: Bites reported higher rates in the province of Los Andes than the average of the country (729 versus 188/100,000), standing out the higher magnitude in 6 to 10 year-old-children. It is noticed that the record is low and incomplete. In this province, no bite control programs or updated studies have been carried out. PMID- 28991317 TI - [Incidence and risk factors for bacteremia on pediatric patients with burns in a specialized care center in Mexico]. AB - BACKGROUND: Bacteremia events are frequent cause of mortality in burn patients and may originate from infected wounds, by bacterial translocation of endogenous microorganisms, from invasive devices or contaminated intravenous solutions. OBJECTIVE: To quantify the incidence of bacteremia in pediatric patients with burns and to identify risk factors. MATERIAL AND METHODS: A prospective cohort study was performed in pediatric patients with burns of Hospital Civil de Guadalajara "Dr. Juan I. Menchaca". Bacteremia was diagnosed by blood cultures in patients with clinical manifestations of sepsis. Risk factors were investigated by multivariate analysis with Cox regression. RESULTS: Were included in the cohort 260 patients, median age 3 years. The incidence of bacteremia was 9.6 events per 1,000 days patient. The most frequently isolated bacteria were Enterobacteriaceae (41.9%), Staphylococcus aureus (22.6%) and Pseudomonas aeruginosa (22.6%). Factors associated with bacteremia were: bums >= 20% TBSA (HR 11.06; 95% CI 4.8-25.4), deep second degree bums or higher (HR 6.9; 95% CI 2.0 23.3) and have had two or less debridement (HR 26.4; 95% CI 8.0-87.7). CONCLUSIONS: Patients with more extensive and deep burns with fewer debridement are at increased risk of bacteremia. PMID- 28991318 TI - [Risk factors for hydatid disease in high school students in the district of Punitaqui, Chile]. AB - BACKGROUND: Hydatidosis is an endemic zoonosis in different areas of Chile, including the Region of Coquimbo, this is linked to the slaughter of cattle and presence of dogs. OBJECTIVE: To identify risk factors related to hydatidosis in the home of high school students of Punitaqui. MATERIAL: A descriptive cross sectional study was done by the application of a self-administered questionnaire to 274 students of high school. The information was analyzed by urban/rural area in five dimensions: knowledge, basic sanitation, keeping dogs, vegetable growing and cattle slaughtering and possession. RESULTS: 84.6% of urban students reported not having received hydatidosis education. In rural areas, 93.5% reported owning dogs, with an average of 2.95 dogs/home (p < 0.001). In urban areas 44.4% of the dogs had not been dewormed and 60.3% (p < 0.001) was fed with viscera in rural areas. The 66.2% of cattle were goats and sheep and 64.5% (p < 0.001) of rural households did slaught. The main way to eliminate viscera was feeding the dogs. CONCLUSIONS: Risk factors that favor the presence of the parasite were present in relation to keeping dogs and cattle breeding and slaughter, which occurred mostly in rural areas, but being also present in urban areas. PMID- 28991319 TI - [Etiology and evolution of the osteoarticular infections. 2009-2015: Pediatric Hospital Pereira Rossell Uruguay]. AB - BACKGROUND: The most frequent osteoarticular infections (OAI) etiological agent is Staphylococcus aureus. The prevalence of other microorganisms has changed after the introduction of new vaccines. AIM: To describe the etiology and evolution of the OAIs in children hospitalized in Pediatric Hospital Pereira Rossell between 2009 and 2015. PATIENTS AND METHODS: Joint fluid and bone puncture studies of hospitalized children suspected of OAI. Epidemiological characteristics, isolated microorganisms, complementary tests, initial treatment, complications, and days of hospitalization were analyzed. RESULTS: 335 patients; the etiology was established in 113. Clinical data could be analyzed in 87 cases. The average age was 6.1 years. They corresponded to: methicillin-sensitive S. aureus (n: 47), community-acquired methicillin-resistant S. aureus (CA-MRSA) (n: 11), Streptococcus pyogenes (n: 6), Streptococcus pneumoniae (n: 1), Haemophilus influenzae type b (n: 2), Gram-negative bacilli (n: 9), Kingella kingae (n: 1) others (n: 6). In 4 cases, more than one microorganism was isolated. CA-MRSA infections were more serious. DISCUSSION: A decrease is observed in the number of CA-MRSA isolates. A fact to be highlighted is the impact of universal vaccination against S. pneumoniae and H. influenzae type b. It is a finding to be monitored the increasing number of Gram-negative bacilli isolates. PMID- 28991320 TI - [Brucellosis in Chile: Description of a series of 13 cases]. AB - INTRODUCTION: Brucellosis is a zoonosis caused by Brucella spp. It may be acquired by consuming unpasteurized dairy products. Brucellosis has a low incidence in Chile, thus, we have a scarce data. AIM: To report and to characterize the first series of clinical cases of adult patients diagnosed with brucellosis in Chile. METHODS: We describe a series of 13 clinical cases in patients diagnosed between 2000 and 2016 in three different centers in the Metropolitan Region, Chile. A retrospective analysis was performed on clinical presentation, laboratory, antibiotic treatment, morbidity and mortality. RESULTS: The mean age was 50 years old. Eight cases had a record of consumption of unpasteurized dairy products. The most frequently reported complaints were fever. The most frequent focal point involved was the spine. Only one patient had a positive blood culture, while the diagnosis was made using serological techniques in the other part of the group. The most indicated antibiotic regimens were doxycycline-rifampicin and doxycycline-gentamicin. The hospital stay was 20 days approximately as an average. Clinical cure was achieved in all cases. CONCLUSIONS: Brucellosis is an infrequent zoonosis in Chile, and it produces a nonspecific clinical picture, so it is necessary to have high suspicion to make the diagnosis based in the antecedent of consumption of unpasteurized dairy or raw meat. PMID- 28991321 TI - [Role of dendritic cells in infection by dengue virus: targets for replication and immune response]. AB - Dengue fever, caused by dengue virus (DENV) infection, is one of the most important diseases in the world, not only due to the high morbidity/mortality rates it causes, but also because of its great economic and social impact in tropical/subtropical countries. DENV infection has a wide range of clinical manifestations ranging from asymptomatic infection or infection with mild symptoms to severe dengue that can lead to death. At present, no etiological treatment or effective globally distributed vaccine against the four DENV serotypes exists. Despite great efforts made to understand the mechanism associated with DENV disease pathogenesis the causes leading to severe dengue presentation have not been clarified. Some hypotheses seek to give a biological and physiological explanation to the clinical manifestations that appear during the infection. Based on the evidence that after contact with dendritic cells DENV alters the functionality of these cells, this review aims to describe the most relevant findings regarding the importance of dendritic cells in the context of DENV infection and progression of the illness. PMID- 28991322 TI - [Rationale of ocular prophylaxis of neonatal ophtalmia in the newborn infant]. PMID- 28991323 TI - [Neonatal infection and universal screening for Streptococcus agalactiae (group B beta-hemolytic Streptococcus) in the pregnant woman: Technical recommendation]. PMID- 28991324 TI - [Neisseria gonorrhoeae]. PMID- 28991325 TI - [About the origin of the term bacteria: a semantic paradox]. AB - This review analyzes the origin of the term "bacteria", which was created by the biologist Christian G. Ehren-berg, initially to account for a single bacterial genus of the Vibrionia family and finally, to explain how this name imposed itself upon others as the formal denomination for the whole bacterial group. PMID- 28991326 TI - [Cerebral hydatid disease: report of six pediatric cases]. AB - Hydatid disease is a parasitic infection whose etiologic agent is Echinococcus granulosus. Human is an accidental intermediate host and the most common site is the liver. The brain involvement is unusual and up to 75% of cases are described in the pediatric population. We present six children with cerebral hydatid disease admitted to the Pediatric Hospital J.P. Garrahan. All had neurological involvement on admission. The images showed single cystic lesion in the brain. They did not present involvement in other organs. Serology was negative in all cases. Medical and surgical treatment in all cases. The clinical outcome was favorable without sequelae in five of them and one had a residual paresis right faciobrachiocrural. This infection should be considered in the differential diagnosis of cystic tumor lesions of the central nervous system. PMID- 28991327 TI - [Delusional parasitosis intestinal and dermatological: clinical cases]. AB - Illusory parasitosis, better known as delusional parasitosis, is a neuropsychiatric syndrome in which patients have the belief of suffering a parasitic disease, that can not be demonstrated after an exhaustive medical study. These patients are characterized by being polyconsultants in different medical specialties and, many of them, have antecedents of psychiatric disorders, some of them undiagnosed. Knowing the existence of the clinical picture, diagnosing early and empathizing with the patient, could give to clinician some clues for a timely and assertive psychiatric referral, and improve patient adherence to the proposed treatment. PMID- 28991328 TI - [Nasal phaeohyphomycosis by Curvularia spicifera in pediatric patient with neutropenia and acute myeloid leukemia]. AB - There are very few reports of pediatric patients with infections by dematiaceous filamentous fungi. In this publication we report a case of invasive fungal infection of the nasal septum by Curvularia spicifera in a pediatric patient with acute myeloid leukemia. The patient presented with a painful scabby wound in the nasal vestibule. Culture and universal PCR were consistent with Curvularia spicifera. Early management with surgical debridement and bi-associated antifungal therapy achieved complete resolution of the lesions, with no evidence of dissemination and relapses. Clinical management of these fungal infections represents a challenge as the antifungal selection and duration of therapy is not yet well stablished. PMID- 28991329 TI - [Surveillance fatigue (fatigatio vigilantiae) during epidemics]. AB - This manuscript presents the concept of "surveillance fatigue" (fatigatio vigilantiae), to describe an epidemiological scenario of an evident underreporting of cases during overwhelming epidemics. We revised past epidemics and found that surveillance fatigue is a common pattern, thus, it may be a useful concept in modern epidemiology. PMID- 28991330 TI - [Longitudinal multicenter analysis of outcomes after cessation of control measures for vancomycin-resistant Enterococci]. PMID- 28991331 TI - [Influenza vaccination of healthcare personnel by work setting and occupation]. PMID- 28991333 TI - Clinical Evaluation of an Extended Depth of Focus Intraocular Lens With the Salzburg Reading Desk. AB - BACKGROUND: Clinical evaluation of an extended depth of focus (EDOF) intraocular lens (IOL) regarding visual performance at various distances, reading performance on an electronic reading desk, and depth of focus on the defocus curve. METHODS: In this prospective study, 30 eyes of 15 patients who received the Tecnis Symfony IOL (Abbott Medical Optics, Inc., Santa Ana, CA) were examined 3.60 +/- 1.54 months postoperatively. Uncorrected and corrected distance (UDVA and CDVA), uncorrected and distance-corrected intermediate (UIVA and DCIVA), and uncorrected and distance-corrected near (UNVA and DCNVA) visual acuity were determined. The defocus curve was performed with distance correction. Furthermore, the reading acuity at the preferred near and intermediate distances was measured with consideration of the reading distance, speed, and print size. A subjective questionnaire was also administered. RESULTS: Results showed a median UDVA of 0.03 logMAR or 20/21.43 Snellen (range: 0.44 to -0.18 logMAR or 20/55.08 to 20/13.21 Snellen), UNVA of 0.20 logMAR or 20/31.70 Snellen (range: 0.46 to 0.00 logMAR or 20/57.68 to 20/20 Snellen), and UIVA of -0.03 logMAR or 20/18.67 Snellen (range: 0.14 to -0.18 logMAR or 20/27.61 to 20/13.21 Snellen). The improved performance at intermediate distance was confirmed by an uncorrected reading acuity of 0.09 logMAR or 20/24.61 Snellen (range: 0.36 to 0.00 logMAR or 20/45.82 to 20/20.00 Snellen) at a preferred intermediate distance of 64.10 cm (range: 52.0 to 75.0 cm). The defocus curve showed an extended range of visual acuity of 0.10 logMAR or better between 1.00 and -1.50 diopters. CONCLUSIONS: The EDOF IOL design provided a wide range of improved visual and reading function between far and intermediate distances and also improved near visual acuity. Patients reported a high rate of satisfaction and spectacle independence at the various distances. [J Refract Surg. 2017;33(10):664-669.]. PMID- 28991332 TI - Visual Performance With Bifocal and Trifocal Diffractive Intraocular Lenses: A Prospective Three-Armed Randomized Multicenter Clinical Trial. AB - PURPOSE: To evaluate and compare quality of vision and reading performance outcomes after implantation of bifocal refractive-diffractive, bifocal apodized diffractive, or trifocal diffractive-refractive intraocular lenses (IOLs). METHODS: This randomized, prospective, three-armed multicenter (Spain, Germany, and France) trial included 104 eyes of 52 patients (mean age: 63.2 +/- 7.7 years). Patients underwent cataract surgery with bilateral implantation of either AT LISA 809M (Carl Zeiss Meditec, Jena, Germany: AT LISA group, 38 eyes), AT LISA tri 839MP (Carl Zeiss Meditec: AT LISA tri group, 32 eyes), or ReSTOR SN6AD1 (Alcon Laboratories, Inc., Fort Worth, TX: ReSTOR group, 34 eyes) IOLs. Visual and refractive outcomes, depth of focus, and reading performance were evaluated at 1, 6, and 12 months postoperatively. RESULTS: The AT LISA tri group showed significantly better 12-month uncorrected (UIVA) and binocular distance-corrected (DCIVA) intermediate visual acuity (P <= .016) than the AT LISA group. The AT LISA tri group showed a significantly better 3-month UIVA compared to the ReSTOR group (P = .042). Binocular uncorrected and corrected distance visual acuities were not significantly different among groups (P >= .092) at the 12-month follow up. A total of 85.3%, 90.0%, and 78.1% of eyes had a spherical equivalent within +/-0.50 D in the AT LISA, AT LISA tri, and ReSTOR groups, respectively, at 12 months (P = .038). No statistically significant differences between the trifocal and bifocal groups were detected for reading performance (P >= .055). CONCLUSIONS: The trifocal diffractive-refractive IOL provides enhanced intermediate visual restoration compared to bifocal diffractive-refractive or apodized diffractive IOLs. The addition of an intermediate focal point did not deteriorate far or near vision. A comparable reading performance was maintained with the trifocal lens. [J Refract Surg. 2017;33(10):655-662.]. PMID- 28991334 TI - Femtosecond Laser-Assisted Capsulotomy: Histological Comparison of Four Different Laser Platforms. AB - PURPOSE: To compare histological analyses of capsulotomies from different laser systems with regard to tissue alteration, laser spot formation, and energy settings. METHODS: Four femtosecond laser platforms approved for cataract surgery were evaluated: LenSx (Alcon Laboratories, Inc., Fort Worth, TX), Catalys (Abbott Medical Optics, Santa Ana, CA), Victus (Tecnolas/Bausch & Lomb, Munich, Germany), and LensAR (Topcon, Gamagori, Japan). Ten human anterior lens capsulotomy disks from each laser system were analyzed: five by means of light microscopy and five by transmission electron microscopy (TEM). TEM was used especially to examine the cellular and stromal changes at the cutting edges. The cellular demarcation line was measured at 15 points along the rim and statistically compared with the findings from all laser platforms. Three capsules of each laser platform were prepared for TEM to evaluate the cellular and tissue edges of the laser cuttings. RESULTS: All capsulotomies revealed a circular demarcation zone of different sizes along the cutting edges. Light microscopy showed a radial tissue damage of 36.0 +/- 12.3 MUm after Victus laser capsulotomy, 8.9 +/- 2.9 MUm after Catalys laser capsulotomy, 25.2 +/- 5.6 MUm after LensAR laser capsulotomy, and 39.8 +/- 5.1 MUm after LenSx laser capsulotomy. Differences between the damaged tissue zones correlated with the laser systems and their energy settings. CONCLUSIONS: The use of less energy and larger spot separation led to smaller collateral damaged tissue areas along the cutting edges. The aberrant laser spots along the cutting edge may result in weakening of the remaining tissue, thereby enhancing the risk for capsular ruptures during surgery. [J Refract Surg. 2017;33(10):670 675.]. PMID- 28991335 TI - Customized Corneal Cross-linking Using Different UVA Beam Profiles. AB - PURPOSE: To evaluate the performance of different customized corneal cross linking (CXL) methods. METHODS: This was a single-center interventional, prospective, longitudinal case series. Four different customized CXL methods were evaluated in keratoconic eyes: (1) uniform (uniform intensity ultraviolet-A [UVA] beam [9 mW/cm2] for 10 minutes) (n = 12 eyes); (2) sector axial map (sector-based UVA irradiation) (n = 12 eyes); (3) ring axial map (concentric rings of UVA beam intensity centered at the steepest curvature of the anterior axial map) (n = 12 eyes); and ring tangential map (same as the ring axial map but centered at the steepest curvature of the anterior tangential map) (n = 14 eyes). Peak UVA energy density in the sector and ring axial map (and ring tangential map) protocols did not exceed 15.0 and 10.8 J/cm2, respectively. A 0.1% riboflavin solution was applied after epithelium removal. Corneal tomography and visual acuity were assessed before and 6 months after CXL. RESULTS: Average and peak energy density was lowest in the ring tangential protocol and highest in the sector axial map group (P < .001). Treated area was lowest in the ring tangential map group and highest in the uniform group (P < .001). Decrease in curvature was similar among the uniform, sector axial map, and ring axial map groups (P < .05). The ring tangential map group had the greatest decrease in curvature per unit energy dose to the cornea (P < .05). Improvement in uncorrected (0.081 +/- 0.056 logMAR) and corrected (0.041 +/- 0.026 logMAR) distance visual acuity per unit energy density was greatest in the ring tangential map group (P > .05). CONCLUSIONS: When normalized to the average energy density, the ring tangential map protocol appeared to provide maximum flattening and improvement in visual acuity. Further studies with larger sample sizes are needed to validate the findings of this pilot study. [J Refract Surg. 2017;33(10):676-682.]. PMID- 28991337 TI - Accuracy of a New Swept-Source Optical Coherence Tomography Biometer for IOL Power Calculation and Comparison to IOLMaster. AB - PURPOSE: To investigate the accuracy of the measurements provided by a new optical biometer (OA-2000, Tomey Corporation, Nagoya, Japan) for calculating the intraocular lens (IOL) power and to compare the refractive outcomes to those obtained with the IOLMaster 500 (Carl Zeiss Meditec, Jena, Germany). METHODS: In this interventional multicenter study, consecutive patients having cataract surgery were enrolled. Only the IOL model used in the largest sample of patients was selected and the eyes implanted with that IOL were subsequently analyzed. The OA-2000, an optical biometer based on swept-source optical coherence tomography (SS-OCT), was used to measure axial length and corneal power in all eyes. IOL power was calculated with the Hoffer Q, Holladay 1, and SRK/T formulas. In a subsample of eyes, the IOL power was also calculated with measurements obtained by partial coherence interferometry (IOLMaster 500). The median absolute error and percentage of eyes with a prediction error of +/-0.50 diopters (D) or less were calculated. RESULTS: Two hundred forty-nine eyes were analyzed. Using SS OCT, the median absolute error ranged between 0.33 (Holladay 1) and 0.35 (SRK/T) D. The rate of eyes with a prediction error of +/-0.50 D or less ranged between 71.5% (Hoffer Q) and 67.1% (SRK/T). In the subsample of 87 eyes with measurements by both devices, the median absolute error was lower with the OA-2000 (Hoffer Q: P = .0377; Holladay 1: P = .0191; SRK/T: P = .0087). CONCLUSIONS: The SS-OCT based optical biometer investigated in the current study provides accurate measurements for IOL power calculation and seems to offer more predictable refractive results compared to the partial coherence interferometry IOLMaster. [J Refract Surg. 2017;33(10):690-695.]. PMID- 28991336 TI - Four-Stage Procedure for Keratoconus: ICRS Implantation, Corneal Cross-linking, Toric Phakic Intraocular Lens Implantation, and Topography-Guided Photorefractive Keratectomy. AB - PURPOSE: To evaluate a four-stage combined treatment for keratoconus including intrastromal corneal ring segment (ICRS) implantation followed by corneal cross linking (CXL), toric phakic intraocular lens (IOL) implantation, and topography guided photorefractive keratectomy (TG-PRK). METHODS: In this retrospective interventional case series, 11 eyes of 7 patients with progressive keratoconus were treated with a four-stage procedure including the following: Keraring ICRS (Mediphacos Ltda, Belo Horizonte, Brazil) implantation followed by CXL, phakic IOL implantation, and TG-PRK (minimum 6 months between each stage). Minimum follow-up was 12 months after TG-PRK. RESULTS: Both mean uncorrected distance visual acuity and corrected distance visual acuity (CDVA) improved from 0.025 decimal (20/800 Snellen) and 0.093 decimal (20/215 Snellen) preoperatively to 0.68 decimal (20/30 Snellen) and 0.73 decimal (20/27 Snellen), respectively, after the combined treatment (P < .0001). Mean postoperative CDVA of 0.73 decimal (20/27 Snellen) was similar to preoperative contact lens CDVA of 0.72 decimal (20/28 Snellen). Mean manifest refraction spherical equivalent reduced from 16.78 +/- 3.58 to 0.59 +/- 0.89 diopters (P < .0001) and mean refractive astigmatism reduced from 5.16 +/- 1.86 to 0.82 +/- 0.28 diopters (P < .0001). CONCLUSIONS: This four-stage procedure appears to be an effective and safe approach for corneal stabilization and improvement of functional vision in patients with keratoconus. Larger case series with a longer follow-up are required to thoroughly evaluate the efficacy, safety, and stability of this combined approach. [J Refract Surg. 2017;33(10):683-689.]. PMID- 28991338 TI - Age-Related Changes in Corneal Astigmatism. AB - PURPOSE: To analyze the changes in corneal astigmatism as a function of age and develop a novel model to estimate corneal astigmatic change according to age. METHODS: This was a cross-sectional study of right eyes of 3,769 individuals. Total corneal astigmatism, keratometric astigmatism, anterior corneal astigmatism, and posterior corneal astigmatism were measured by a Scheimpflug tomographer. Smoothing fitting curves of polar values of corneal astigmatism as a function of age were drawn and average changes in corneal astigmatism at different ages were calculated. RESULTS: Two turning points of age on total corneal astigmatism were 36 and 69 years. The average change of total corneal astigmatism toward against-the-rule astigmatism was 0.13 diopters (D)/10 years from 18 to 35 years, 0.45 D/10 years from 36 to 68 years, and decreased after 69 years, mainly caused by anterior corneal astigmatism. The mean magnitude of posterior corneal astigmatism was -0.33 D and exceeded 0.50 D in 14.27% of eyes. The vectorial difference between total corneal astigmatism and keratometric astigmatism was correlated with posterior corneal astigmatism, polar value of anterior corneal astigmatism, age, and corneal higher order aberrations (r = 0.636; standard partial regression coefficients were 0.479, -0.466, 0.282, and 0.196, respectively; all P < .001). Based on the non-linear model to estimate corneal astigmatic change with age, a formula was developed to calculate recommended correction of astigmatism according to age and astigmatic type. CONCLUSIONS: The rate of change of total corneal astigmatism showed a non-linear trend toward against-the-rule astigmatism, which was low at young and old age, high at middle age, and should be taken into account when performing surgery to correct astigmatism. [J Refract Surg. 2017;33(10):696-703.]. PMID- 28991339 TI - Pupil Dynamics Induced by Light Reflex After Posterior Chamber Phakic Intraocular Lens Implantation. AB - PURPOSE: To assess the light reflex of the pupil after Implantable Collamer Lens (ICL) (KS-aquaPORT; STAAR Surgical, Nidau, Switzerland) implantation to determine whether the ICL implantation might affect the pupil dynamics. METHODS: This study examined 28 eyes of 28 consecutive patients who underwent implantation of the posterior phakic ICL for the correction of myopia and astigmatism. Patient age at the time of surgery was 31.1 +/- 6.8 years (range: 25 to 42 years). Preoperative refraction was -7.38 +/- 2.26 diopters (D) (range: -3.25 to -11.80 D). Light reflex was evaluated using the infrared pupillometer Iriscorder C7364 (Hamamatsu Photonics, Hamamatsu, Japan). Measured parameters included pupil diameter (D1), constriction ratio, maximum constriction velocity, maximum dilation velocity, and the time required to recover 63% of the pupil diameter (T5). At 6 months postoperatively, the authors also investigated the relationship with the amount of vault using the Pentacam (Oculus Optikgerate, Wetzlar, Germany). Evaluations with the instrument were performed before and at 1, 3, and 6 months after surgery. RESULTS: There was no significant association found between any of the parameters (analysis of variance, D1: P = .99, constriction ratio: P = .59, maximum constriction velocity: P = .87, maximum dilation velocity: P = .13, T5: P =.57). The vault of the ICL at 6 months postoperatively was 382.1 +/- 176.5 MUm. There were no significant associations between the maximum constriction velocity, maximum dilation velocity, and amount of vaulting (Spearman correlation coefficient maximum constriction velocity: r = 0.07, P = .71, maximum dilation velocity: r = 0.26, P = .28). CONCLUSIONS: The light reflex of the pupillary dynamics continued to be maintained at 6 months after ICL implantation. Current findings also verified that ICL implantation had little influence on the postoperative function of the iris. [J Refract Surg. 2017;33(10):704-707.]. PMID- 28991340 TI - Comparison of Corneal Endothelial Cell Loss Between Two Femtosecond Laser Platforms and Standard Phacoemulsification. AB - PURPOSE: To analyze and compare the changes in endothelial cell density (ECD) and cumulative dissipated energy (CDE) in patients having cataract surgery with two different femtosecond laser platforms and standard phacoemulsification. METHODS: This prospective non-randomized comparative study included patients scheduled to undergo cataract extraction using femtosecond laser-assisted cataract surgery (FLACS) (60 eyes) or standard phacoemulsification (60 eyes) between September 2013 and March 2016. The main outcome measures were CDE and percentage of endothelial cell loss. Comparative analysis of CDE and percentage of endothelial cell loss between the two phacoemulsification platforms with respect to conventional and FLACS techniques was performed. RESULTS: The CDE and the 1-month mean percentage of endothelial cell loss was 6.11 +/- 3.52 and 9.06% +/- 8.77% in the standard phacoemulsification group and 4.65 +/- 3.61 and 6.00% +/- 8.02% in the FLACS group, respectively (P = .039). In the subgroup analysis based on cataract grading, the CDE was significantly less in the FLACS group compared to the standard phacoemulsification group in both the early and advanced cataract group (P = .002). The percent decrease in endothelial cell loss was statistically lower in the FLACS group when compared to the standard phacoemulsification group in the advanced cataract subgroup (P = .02). CONCLUSIONS: FLACS pretreatment resulted in a decrease in CDE and less endothelial cell loss when compared to standard phacoemulsification. The decrease in endothelial cell loss was more prominent in the denser cataract group; thus, FLACS may be most beneficial in those cases. There was no significant difference in results between the two laser platforms. [J Refract Surg. 2017;33(10):708-712.]. PMID- 28991341 TI - Repair of Irregularly Irregular Astigmatism by Transepithelial Phototherapeutic Keratectomy. AB - PURPOSE: To evaluate the outcome of transepithelial phototherapeutic keratectomy (PTK) in the management of irregularly irregular astigmatism. METHODS: This was a case series of two patients who underwent transepithelial PTK for irregularly irregular astigmatism. In the first case, the patient complained of diplopia due to corneal scarring caused by a metallic foreign body injury. The topography demonstrated irregularly irregular astigmatism with significant asymmetry in the inferotemporal to superonasal axis. In the second case, the patient complained of blurred vision and ghosting caused by significant central epithelial ingrowth through a buttonhole LASIK flap, which was causing a localized irregularity on topography. Due to the localized nature of the irregularities, a transepithelial PTK treatment was preferred to custom ablation given the degree of epithelial masking present. RESULTS: Transepithelial PTK was performed in both cases using the Schwind Amaris 500E excimer laser (Schwind eye-tech-solutions, Kleinostheim, Germany) and an 8-mm optical zone. The ablation depth was planned to reach the depth of the epithelium using a stepwise protocol, reviewing the pattern of the remaining epithelium and regularity of the stromal surface between each ablation. A marked improvement in the regularity of the topography was achieved in both cases, with only regular astigmatism remaining. Both patients reported a subjective improvement in quality of vision and the corrected distance visual acuity improved by one and two lines, respectively. CONCLUSIONS: Transepithelial PTK was effective in treating these cases of localized irregularly irregular astigmatism, achieving both objective and subjective improvement in vision. Compensatory epithelial remodeling over the irregularities enabled the transepithelial PTK approach to target the stromal surface irregularities. [J Refract Surg. 2017;33(10):714-719.]. PMID- 28991342 TI - Reduction of Consecutive Esotropia Using Modified Contralateral Recession and Resection for Recurrent Intermittent Exotropia. AB - PURPOSE: To report consecutive esotropia in contralateral lateral rectus recession and medial rectus resection for recurrent intermittent exotropia after unilateral lateral rectus recession and medial rectus resection and to evaluate the surgical outcome of modified contralateral lateral rectus recession and medial rectus resection for exotropia after unilateral lateral rectus recession and medial rectus resection. METHODS: A total of 36 patients were included in this retrospective study. As a primary surgery for exotropia, all patients underwent unilateral lateral rectus recession and medial rectus resection on the non-dominant eye. Patients were subsequently assigned to either conventional contralateral lateral rectus recession and medial rectus resection (surgical dosages based on Wright's surgical table) (n = 19; conventional group) or modified contralateral lateral rectus recession and medial rectus resection (surgical dosages reduced by 5 prism diopters on Wright's surgical table) (n = 17; modified group) for recurrent exotropia. Surgical success rates were evaluated. Reoperation or prism glasses prescription rates due to consecutive esotropia were evaluated. RESULTS: The mean follow-up durations after reoperation were 25.8 and 24.0 months in the conventional and modified groups, respectively. The surgical success rates were 73.7% and 82.4% (P = .538, Fisher's exact test) and the recurrence rates were 0% and 17.6% (P = .059, Fisher's exact test), respectively. The reoperation or prism glasses prescription rates due to consecutive esotropia were 26.3% and 0%, respectively (P = .025, Fisher's exact test). CONCLUSIONS: Final outcomes were better in the modified group compared to the conventional group. Consecutive esotropia was significantly more frequent in the conventional group than in the modified group. In surgery for recurrent exotropia, a reduction of the surgical dosage will reduce the incidence of consecutive esotropia. [J Pediatr Ophthalmol Strabismus. 2018;55(1):53-58.]. PMID- 28991343 TI - Endophthalmitis Following Pediatric Cataract Surgery: An International Pediatric Ophthalmology and Strabismus Council Global Perspective. AB - PURPOSE: To compile international data on the risk factors, diagnosis, and treatment of endophthalmitis following pediatric cataract surgery. METHODS: An e mail containing a link to an online survey was sent to all members of the American Association for Pediatric Ophthalmology and Strabismus. The questionnaire examined the incidence, risk factors, treatment, outcomes, and prophylaxis of endophthalmitis following pediatric cataract surgery around the world. RESULTS: Two hundred thirty-seven ophthalmologists answered the questionnaire. Eight ophthalmologists (3.4%) encountered 22 cases of endophthalmitis following pediatric cataract surgery during their practice. Most patients with endophthalmitis following pediatric cataract surgery were 2 to 4 years of age (36.4%). An intraocular lens was implanted in 59.1% of cases, most of which were acrylic intraocular lenses (53.8%). The main presenting symptoms were photophobia (50%) and pain (40.9%). The most common signs were conjunctival injection (36.4%) and hypopyon (31.8%). The final visual acuity was counting fingers or worse in 86% of cases. The most common cultured organism was Staphylococcus aureus (31.8%). The most common management of endophthalmitis following pediatric cataract surgery was a combination of intravitreal, systemic, and topical antibiotics (36.4%). Most ophthalmologists (68.2%) administered prophylactic intracameral antibiotic treatment during surgery and 50% used vancomycin. CONCLUSIONS: Endophthalmitis following pediatric cataract surgery is an uncommon, multifactorial complication with poor visual prognosis. Efforts directed at minimizing its risk, such as treating potential predisposing systemic conditions, improving sterilization techniques, optimizing operative conditions to reduce complications and surgery duration, and using subconjunctival and intracameral antibiotics, decrease its incidence. Early postoperative evaluation, subsequent follow-up visits, and keeping a high index of suspicion should facilitate the recognition of endophthalmitis following pediatric cataract surgery to avoid delaying treatment. [J Pediatr Ophthalmol Strabismus. 2018;55(1):23-29.]. PMID- 28991344 TI - Combined Oral and Topical Beta Blockers for the Treatment of Early Proliferative Superficial Periocular Infantile Capillary Hemangioma. AB - PURPOSE: To evaluate the safety and efficacy of combined oral and topical beta blockers for the treatment of superficial periocular infantile hemangioma at the early proliferative stage. METHODS: This was a randomized, controlled comparison trial involving 25 patients. Patients were randomly enrolled into two groups: the topical and systemic treatment and systemic treatment only groups. The topical and systemic treatment group was treated with oral propranolol (1 mg/kg per day initially, increased to 2 mg/kg per day gradually in 2 weeks) and timolol maleate 0.5% gel. The systemic treatment only group received oral propranolol (1 mg/kg per day initially, increased to 2 mg/kg per day gradually in 2 weeks) and simple eye ointment to be applied to the lesion. The Hemangioma Activity Score was used to record the proliferative activity of the hemangioma. The main outcomes of the study were the change in the hemangioma size, the proliferative activity, and the treatment side effects. RESULTS: At the end of the treatment period, the Hemangioma Activity Score was significantly improved in both groups from their values before treatment. However, the score obtained after treatment was significantly better in the topical and systemic treatment group (P < .05). Regarding the response to treatment, 10 and 3 cases in the topical and systemic treatment and systemic treatment only groups, respectively, showed a good response, with a significant difference between the two groups (P < .50). There were no recorded serious local or systemic complications during treatment in either group. CONCLUSIONS: The results from combining topical with oral beta blockers showed that topical beta blockers are of additive value in treating superficial periocular infantile hemangioma in the early proliferative stage. [J Pediatr Ophthalmol Strabismus. 2018;55(1):37-42.]. PMID- 28991346 TI - Surgical Outcome of Intermittent Exotropia With Improvement in Control Grade Subsequent to Part-time Preoperative Occlusion Therapy. AB - PURPOSE: To evaluate the effect of improvement in the control grade of intermittent exotropia using part-time occlusion therapy on the final postoperative outcome. METHODS: Control of intermittent exotropia was graded as good, fair, or poor in 89 consecutive patients with intermittent exotropia during their first visit. The patients were reevaluated after part-time preoperative occlusion therapy and divided into two groups (improvement and no improvement) according to whether they showed improvement in control grade. The surgical success rate was compared retrospectively between the two groups. RESULTS: The mean angle of deviation on the first visit was 27.61 +/- 5.40 prism diopters (PD) at distance and 29.82 +/- 5.28 PD at near. There were significant improvements in the angles of deviation for distance (26.17 +/- 5.09 PD) and near (27.26 +/- 5.56 PD) after part-time occlusion (both P < .001). The 49 patients who had a significantly improved control grade had a significantly better surgical success rate (77.6%) than the 40 patients who did not (50%; P = .007). CONCLUSIONS: Part time occlusion therapy improves the control grade of intermittent exotropia, leading to a better likelihood of successful surgery and a reduction of the angles of deviation for distance and near. [J Pediatr Ophthalmol Strabismus. 2018;55(1):59-64.]. PMID- 28991345 TI - The Efficacy of Bilateral Lateral Rectus Recession According to Secondary Deviation Measurements in Unilateral Exotropic Duane Retraction Syndrome. AB - PURPOSE: To evaluate the surgical results of asymmetric bilateral lateral rectus recession in exotropic Duane retraction syndrome with abnormal face turn toward the opposite side according to secondary deviation measurements. METHODS: Retrospective chart review. RESULTS: Seven cases of unilateral exotropic Duane retraction syndrome were reviewed. All cases had globe retraction on adduction and exotropia with limited adduction, five of which also had mild limitation of abduction. Four cases had upshoot/downshoot on adduction and all patients had face turn. Exotropia was measured in forced primary position. The average lateral rectus recession was 6.36 mm (range: 5.5 to 7.5 mm) in the affected eye and 7.36 mm (range: 6.5 to 8.5 mm) in the healthy eye. The mean follow-up period was 282 days. Mean exotropia in the forced primary position improved from 27.9 +/- 5.7 prism diopters (PD) preoperatively to 7.9 +/- 16.8 PD postoperatively (P = .025). Head position resolved completely in all but one case (P =.031). There were no significant changes in ductions. CONCLUSIONS: The results suggest that asymmetric bilateral lateral rectus recession in exotropic Duane retraction syndrome with abnormal head turn posture successfully eliminates abnormal head turn posture and exotropia in most cases. [J Pediatr Ophthalmol Strabismus. 2018;55(1):47-52.]. PMID- 28991347 TI - Medial Rectus Bridge Faden Operations in Accommodative and Partially Accommodative Esotropia With Convergence Excess. AB - PURPOSE: To evaluate the results of the bilateral bridge Faden operation on the medial rectus muscles with and without recession in the treatment of accommodative and partially accommodative esotropia with convergence excess. METHODS: A retrospective analysis was performed on the medical records of 103 patients who underwent the bridge Faden operation on both medial rectus muscles, with or without recession, for the treatment of accommodative and partially accommodative esotropia with convergence excess. Preoperative and postoperative near and distance deviations and near-distance disparities were evaluated. RESULTS: The study population consisted of 38 (37%) girls and 65 (63%) boys. The mean age was 9.32 +/- 5.83 years (range: 1 to 18 years) and the mean follow-up period was 14.49 +/- 2.78 months. Fifty-one patients underwent the bridge Faden operation on both medial rectus muscles with recession (recession group) and 52 patients underwent the bridge Faden operation on both medial rectus muscles without recession (no recession group). The mean preoperative amount of esotropia at near was 43.51 +/- 7.00 and 24.24 +/- 3.56 prism diopters (PD) for the recession and no recession groups, respectively. The mean preoperative amount of esotropia at distance was 26.63 +/- 6.86 and 9.22 +/- 2.09 PD for both groups, respectively. The mean preoperative near-distance disparity was 17.14 +/- 3.00 and 14.05 +/- 4.14 PD for both groups, respectively. In both groups, there was a statistically significant difference in the near and distance deviations and the near-distance disparity between preoperative and postoperative values (P < .05). Postoperatively, there was no significant difference between 1 month, 6 months, and 1 year and between 6 months and 1 year (P > .05). CONCLUSIONS: The bridge Faden operation on both medial rectus muscles either with or without recession was a successful surgical procedure in patients with accommodative and partially accommodative esotropia. During the follow-up period, the success rates did not decrease. [J Pediatr Ophthalmol Strabismus. 2017;54(6):369-374.]. PMID- 28991348 TI - Inferior Oblique Belly Transposition for Small Angle Hypertropia With Inferior Oblique Overaction: A Pilot Study. AB - PURPOSE: To evaluate the efficacy of transposition of the belly of the inferior oblique muscle in treating inferior oblique overaction with small angle hypertropia. METHODS: The medical records of 10 patients who underwent inferior oblique belly transposition from March 2014 to July 2016 were reviewed. Transposition of the inferior oblique muscle belly consisted of suturing the entire body of the muscle to the sclera 5 mm posterior to the temporal insertion of the inferior rectus muscle. All patients had small hypertropias (< 5 prism diopters) in the primary gaze position with associated inferior oblique overaction. Deviations in both primary and lateral gazes, compensatory face turns or head tilts, and the degree of inferior oblique overaction were evaluated preoperatively and postoperatively. RESULTS: Nine of the 10 patients had a complete resolution of inferior oblique overaction. In the remaining patient, the inferior oblique overaction improved from +3 to +1. None of the patients had any residual vertical deviation. There was elimination of compensatory head tilting in 5 patients and correction of compensatory face turns in 4 patients. One patient with mild up drifting of the involved eye also improved after the procedure. All patients expressed subjective satisfaction with the surgical outcome. CONCLUSIONS: Transposition of the inferior oblique muscle belly effectively weakened mild to moderate inferior oblique overaction and corrected small primary position hypertropias. This procedure may be a useful addition to surgical treatment options in patients with small hypertropias associated with inferior oblique overaction. [J Pediatr Ophthalmol Strabismus. 2018;55(1):43 46.]. PMID- 28991349 TI - Surgical Outcome of Congenital Cataract in Eyes With Microcornea. AB - PURPOSE: To report the intraoperative and postoperative outcomes of congenital cataract surgery in eyes with microcornea. METHODS: In this retrospective, interventional, comparative case series, the authors reviewed 47 eyes of 26 children with microcornea and congenital cataract (21 bilateral and 5 unilateral) who underwent lens aspiration with primary posterior capsulectomy and anterior vitrectomy between 2008 and 2014 with a minimum follow-up period of 6 months. Demographic profiles and systemic and ocular features were documented. Intraoperative and postoperative complications were studied separately for bilateral and unilateral cases. Patients were also divided into two groups on the basis of their ages at surgery (early surgery group: 3 months or younger; late surgery group: older than 3 months) and postoperative complications were compared. Visual outcome was analyzed in those with a follow-up period of more than 1 year. RESULTS: Early surgery was performed in 24 eyes of 13 patients (11 bilateral and 2 unilateral) and late surgery in 23 eyes of 13 patients (10 bilateral and 3 unilateral). Intraoperatively, all eyes had poor pupillary dilatation and 6 (12.8%) eyes needed iris hooks. Postoperatively, the most common early complication was transient corneal edema observed in 22 (46.8%) eyes (13 and 8 eyes in the early and late surgery groups, respectively). Late complications included visual axis opacification in 6 (12.76%) eyes (3 in each group), and secondary glaucoma in 5 (10.64%) eyes (2 and 3 eyes in the early and late surgery groups, respectively). Vision was normal for age in 18 (60%) of the bilateral cases with a follow-up period of more than 1 year. CONCLUSIONS: Early surgical intervention for congenital cataract in eyes with microcornea can result in favorable outcomes with an acceptable rate of postoperative complications. [J Pediatr Ophthalmol Strabismus. 2018;55(1):30-36.]. PMID- 28991350 TI - Neuroanatomical Structures in Human Extraocular Muscles and Their Potential Implication in the Development of Oculomotor Disorders. AB - The potential role of sensory feedback from human extraocular muscles has been subjected to considerable speculation in the ophthalmic literature. Extraocular muscles pull against a fairly even load and do not initiate a stretch reflex, even when the eyes are directed toward the boundaries of their respective field of action. These unique working conditions and physiological properties have led to the notion that the sensory signal arising from receptors in extraocular muscles differs from the conventional proprioceptive signal arising from their somatic counterparts. The interest in the receptors at the myotendinous junction of human extraocular muscles has been renewed due to their alleged role in the development of binocular vision and their potential implication in the etiology of binocular vision anomalies. The idea that extraocular muscles provide knowledge of eye position and whether this function can be affected by surgical intervention has initiated several clinical and neuroanatomical studies. Many of these studies support this concept and suggest that surgical procedures that impose only minimal interference with the proprioceptive signal will give a better postoperative result. However, other studies contradict this view because the afferent capacity of the receptors can be questioned and some uncertainties remain. The purpose of this study was to review the related literature and discuss the possible role of ocular proprioceptors in relation to binocular vision and the development of eye motility disorders. [J Pediatr Ophthalmol Strabismus. 2018;55(1):14-22.]. PMID- 28991351 TI - The Treatment of Congenital Nasolacrimal Duct Obstruction in Children: A Retrospective Review. AB - PURPOSE: To compare success and extrusion rates of the monocanalicular and bicanalicular Crawford intubation systems (JEDMED Instrument Company, St. Louis, MO). METHODS: A retrospective review of all children who were diagnosed as having congenital nasolacrimal duct obstruction and treated with lacrimal intubation from 2005 to 2014 was performed. The total number of eyes included was 168 (75 and 93 right and left eyes, respectively). Bicanalicular intubation was used in 80 eyes (bicanalicular group) and monocanalicular intubation was used in 88 eyes (monocanalicular group). RESULTS: Success occurred in 63 (78.75%) and 82 (93.18%) eyes in the bicanalicular and monocanalicular groups, respectively (P = .00653). Extrusion occurred in 24 (30%) and 11 (12.5%) eyes, respectively (P = .00528). CONCLUSIONS: Monocanalicular intubation for congenital nasolacrimal duct obstruction is superior to bicanalicular intubation. Extrusion and reoperation rates are significantly lower. [J Pediatr Ophthalmol Strabismus. 2018;55(1):65 67.]. PMID- 28991352 TI - Optical Coherence Tomography-Assisted Limbal Dermoid Removal. AB - This report and accompanying video show the novel use of intraoperative optical coherence tomography (OCT) in the excision of a limbal dermoid. Examining for residual opaque tissue in the cornea accompanied by OCT imaging is a useful technique to confirm complete excision of the lesion. [J Pediatr Ophthalmol Strabismus. 2017;54:e58-e59.]. PMID- 28991353 TI - Asymptomatic Leukemic Optic Nerve Infiltration as Presentation of Acute Lymphoblastic Leukemia Relapse. AB - The authors report a case of asymptomatic leukemic optic neuropathy as the first sign of acute lymphoblastic leukemia relapse in a 4-year-old boy. Routine ophthalmologic examination showed normal visual acuity and pupillary function in the presence of a tumoral mass covering the left optic disc. The mass resolved with preservation of vision after intrathecal chemotherapy. A routine ophthalmological examination is recommended for all patients with a history of acute lymphoblastic leukemia to exclude optic nerve involvement without systemic symptoms or signs. Vision can be preserved and radiation avoided by using targeted chemotherapy. [J Pediatr Ophthalmol Strabismus. 2017;54:e60-e62.]. PMID- 28991354 TI - Anteriorization of the Normally Acting Inferior Oblique Muscles to Treat Dissociated Vertical Deviation Associated With Juvenile Glaucoma. AB - A case of dissociated vertical deviation, ptosis, and juvenile glaucoma is described. J deformity anteriorization of the normally acting inferior oblique muscles was chosen to preserve the superior fornix for glaucoma surgeries by avoiding superior rectus recession and to prevent narrowing of the palpebral fissure by avoiding an inferior rectus tuck. [J Pediatr Ophthalmol Strabismus. 2017;54:e63-e66.]. PMID- 28991355 TI - A Case of Orbital Lipoblastoma: Temporal Evolution of Imaging Findings. AB - Lipoblastoma is a rare tumor that is not commonly seen in the orbit. The authors present clinical features, histopathologic findings, changes in the radiologic findings over time, and the radiological-pathological correlation of orbital lipoblastoma in an infant. A 3-month-old male infant presented with a palpable mass on the left upper eyelid. The patient was observed for 1 year with magnetic resonance imaging. At the age of 15 months, the patient underwent excisional biopsy. Histopathologic examination showed features of hypocellular lobules with a mixture of adipocytes of various stages of maturity and myxoid stroma separated by prominent fibrous septa, confirming a diagnosis of orbital lipoblastoma. [J Pediatr Ophthalmol Strabismus. 2017;54:e67-e70.]. PMID- 28991356 TI - Antioxidant Capacity In Vitro and In Vivo of Various Ecotypes of Mexican Plum (Spondias purpurea L.). AB - Spondias purpurea L. is a fruit native to Mexico, however, it is found as far away as Brazil. It possesses a high commercial potential owing to its sensorial and nutritional qualities and its low cost of production. There exists a variety of ecotypes that have not been characterized and their adequate selection process, according to their strongest functional characteristics, will allow the establishment of improvement programs for this genetic resource. The object of this study was the chemical characterization and the determination of the in vitro and in vivo antioxidant capacity of 7 Spondias purpurea L. ecotypes. Differences were observed in the antioxidant capacity and the content of functional compounds among all the ecotypes analyzed. A high total phenolic content and a low flavonoid and carotenoid content were found, both in the epicarp and in the pulp. In each ecotype, the hydrophilic phase presented up to 40 times greater antioxidant capacity compared to the lipophilic phase. The hydrophilic phase of the epicarp of "Costena Tierra Colorada" had the greatest antioxidant capacity and highest total phenolic content, whereas "Jocote" presented the lowest antioxidant capacity and total phenolic content. A positive correlation was observed between phenol levels and the antioxidant capacity in the epicarp. Regarding antioxidant activity in vivo, it was observed that in all analyzed concentrations of hydrophilic extracts of the epicarp of "Costena Tierra Colorada" and in the highest "Jocote" concentrations, they provided thermo protection against heat stress as well as a general well-being to the worm as evidenced by their high mobility. PMID- 28991357 TI - The prevalence of psychological comorbidity in people with vitiligo: a systematic review and meta-analysis. AB - BACKGROUND: Vitiligo is a chronic disorder causing skin depigmentation with global prevalence varying from 0.2% to 1.8%. U.K. guidelines recommend assessment of psychological state during clinical evaluation of vitiligo. However, the prevalence of psychological comorbidity in people with vitiligo has not been described. OBJECTIVES: To establish the prevalence of psychological symptoms or disorders in people with vitiligo and describe the outcome measures used. METHODS: We performed a comprehensive search of MEDLINE, Embase, CINAHL and PsycINFO to identify observational studies assessing the prevalence of psychological symptoms or disorders (December 2016). DerSimonian and Lard random effects models were used to estimate the overall pooled prevalence. RESULTS: We identified 29 studies with 2530 people with vitiligo. Most studies included a measure of either depression (n = 25) or anxiety (n = 13). The commonest tools were the Hospital Anxiety and Depression Scale and the Centre for Epidemiology Studies Depression Scale. Ten studies provided information on 13 other psychological outcomes. Pooled prevalence using depression-specific and anxiety specific questionnaires was 0.29 [95% confidence interval (CI) 0.21-0.38] and 0.33 (95% CI 0.18-0.49), respectively. Prevalence was lower for clinically diagnosed depression (0.21, 95% CI 0.15-0.28) and anxiety (0.15, 95% CI 0.06 0.24). When nonspecific tools were used the prevalence remained similar for depression (0.27, 95% CI 0.08-0.46) but increased for anxiety (0.46, 95% CI 0.39 0.52). High heterogeneity was observed. CONCLUSIONS: A range of psychological outcomes are common in people with vitiligo. The prevalence of anxiety was influenced by type of screening tool, suggesting the need for validation of psychological outcome screening tools in the field of dermatology. PMID- 28991358 TI - An Expanded View of Joint Attention: Skill, Engagement, and Language in Typical Development and Autism. AB - This study provides an expanded view of joint attention and its relation to expressive language development. A total of 144 toddlers (40 typically developing, 58 with autism spectrum disorder [ASD], 46 with developmental delay [DD]) participated at 24 and 31 months. Toddlers who screened positive for ASD risk, especially those subsequently diagnosed with ASD, had poorer joint attention skills, joint engagement during parent-toddler interaction, and expressive language. Findings highlight the dynamic relation between joint attention and language development. In the ASD and DD groups, joint engagement predicted later expressive vocabulary, significantly more than predictions based on joint attention skills. Joint engagement was most severely impacted when toddlers did not talk initially and improved markedly if they subsequently began to speak. PMID- 28991359 TI - Association between the gut microbiota and mineral metabolism. AB - The aim of this review is to present the most recent scientific evidence of interactions between the intestinal microbiota and minerals, and the effect of this interaction on the health of the host. The Web of Science database from the years 2013-2017 on this topic was reviewed. Numerous in vitro studies have shown that iron significantly affects the intestinal microbiota. However, Bifidobacteriaceae are capable of binding iron in the large intestine, thereby limiting the formation of free radicals synthesized in the presence of iron, and thus reducing the risk of colorectal cancer. Animal studies have revealed that supplementation with probiotics, prebiotics and synbiotics has a significant effect on bone calcium, phosphate and bone metabolism. The dynamic interaction between microbiota and zinc was shown. Human studies have provided evidence of the influence of probiotic bacteria on parathormone, calcium and phosphate levels and thus on bone resorption. Recent studies have produced new information mainly on the impact of the intestinal bacteria on the metabolism of calcium and iron. From a scientific perspective, the most urgent fields that remain to be investigated are the identification of all human gut microbes and new therapies targeting the interaction between intestinal bacteria and minerals. (c) 2017 Society of Chemical Industry. PMID- 28991360 TI - Low-dose naltrexone: a novel treatment for Hailey-Hailey disease. AB - Hailey-Hailey disease (chronic benign familial pemphigus) is a rare inherited dermatosis typically characterized by erosions at intertriginous sites preceded by minor trauma or stress. We report a case of treatment-resistant Hailey-Hailey disease having failed topical and oral steroids, prophylactic aciclovir and doxycycline, and systemic therapies including dapsone, acitretin and ciclosporin. Low-dose naltrexone 4.5 mg once daily was commenced following an incidental benefit in this patient's similarly affected sister. The clinical and psychological response to date has been considerable. PMID- 28991361 TI - WITHDRAWN: Anticonvulsants for fibromyalgia. AB - BACKGROUND: Fibromyalgia (FM) is a clinically well-defined chronic condition of unknown aetiology characterised by chronic widespread pain that often co-exists with sleep problems and fatigue. People often report high disability levels and poor health-related quality of life (HRQoL). Drug therapy focuses on reducing key symptoms and disability, and improving HRQoL. Anticonvulsants (antiepileptic drugs) are drugs frequently used for the treatment of chronic pain syndromes. OBJECTIVES: To assess the benefits and harms of anticonvulsants for treating FM symptoms. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 8, 2013), MEDLINE (1966 to August 2013), PsycINFO (1966 to August 2013), SCOPUS (1980 to August 2013) and the reference lists of reviewed articles for published studies and www.clinicaltrials.gov (to August 2013) for unpublished trials. SELECTION CRITERIA: We selected randomised controlled trials of any formulation of anticonvulsants used for the treatment of people with FM of any age. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted the data of all included studies and assessed the risks of bias of the studies. We resolved discrepancies by discussion. MAIN RESULTS: We included eight studies: five with pregabalin and one study each with gabapentin, lacosamide and levetiracetam. A total of 2480 people were included into anticonvulsants groups and 1099 people in placebo groups. The median therapy phase of the studies was 13 weeks. The amount and quality of evidence were insufficient to draw definite conclusions on the efficacy and safety of gabapentin, lacosamide and levetiracetam in FM. The amount and quality of evidence was sufficient to draw definite conclusions on the efficacy and safety of pregabalin in FM. Therefore, we focused on our interpretation of the evidence for pregabalin due to our greater certainty about its effects and its greater relevance to clinical practice. All pregabalin studies had a low risk of bias. Reporting a 50% or greater reduction in pain was more frequent with pregabalin use than with a placebo (risk ratio (RR) 1.59; 95% confidence interval (CI) 1.33 to 1.90; number needed to treat for an additional beneficial outcome (NNTB) 12; 95% CI 9 to 21). The number of people who reported being 'much' or 'very much' improved was higher with pregabalin than with placebo (RR 1.38; 95% CI 1.23 to 1.55; NNTB 9; 95% CI 7 to 15). Pregabalin did not substantially reduce fatigue (SMD -0.17; 95% CI -0.25 to -0.09; 2.7% absolute improvement on a 1 to 50 scale) compared with placebo. Pregabalin had a small benefit over placebo in reducing sleep problems by 6.2% fewer points on a scale of 0 to 100 (standardised mean difference (SMD) -0.35; 95% CI -0.43 to -0.27). The dropout rate due to adverse events was higher with pregabalin use than with placebo use (RR 1.68; 95% CI 1.36 to 2.07; number needed to treat for an additional harmful outcome (NNTH) 13; 95% CI 9 to 23). There was no significant difference in serious adverse events between pregabalin and placebo use (RR 1.03; 95% CI 0.71 to 1.49). Dizziness was reported as an adverse event more frequently with pregabalin use than with placebo use (RR 3.77; 95% CI 3.06 to 4.63; NNTH 4; 95% CI 3 to 5). AUTHORS' CONCLUSIONS: The anticonvulsant, pregabalin, demonstrated a small benefit over placebo in reducing pain and sleep problems. Pregabalin use was shown not to substantially reduce fatigue compared with placebo. Study dropout rates due to adverse events were higher with pregabalin use compared with placebo. Dizziness was a particularly frequent adverse event seen with pregabalin use. At the time of writing this review, pregabalin is the only anticonvulsant drug approved for treating FM in the US and in 25 other non-European countries. However, pregabalin has not been approved for treating FM in Europe. The amount and quality of evidence were insufficient to draw definite conclusions on the efficacy and safety of gabapentin, lacosamide and levetiracetam in FM. PMID- 28991362 TI - Axillary tumour burden in women with a fine-needle aspiration/core biopsy-proven positive node on ultrasonography compared to women with a positive sentinel node. AB - BACKGROUND: The sensitivity of axillary ultrasonography (AUS) has increased in recent years, enabling detection of even low-volume axillary nodal metastases. The aim here was to evaluate the axillary tumour burden in women with a fine needle aspiration/core biopsy-proven positive node on AUS and in those with a positive sentinel node biopsy (SNB). METHODS: This retrospective cohort study included all patients with early breast cancer who had AUS and axillary lymph node dissection (ALND) between 2011 and 2014. RESULTS: A total of 332 patients who had ALND were eligible for the study, 191 (57.5 per cent) in the AUS-positive group and 141 (42.5 per cent) in the SNB-positive group. Patients in the AUS positive group were older at diagnosis (P = 0.018), more likely to have larger tumours (P = 0.002), higher tumour grade (P = 0.005), positive human epidermal growth factor 2 status (P = 0.015), and negative oestrogen receptor status (P < 0.001). The AUS-positive group also had a larger number of lymph nodes with macrometastases (P < 0.001) and were more likely to have extranodal invasion (P < 0.001). In the AUS-positive group, 40.3 per cent of patients (77 of 191) had only one or two nodes with macrometastases identified at histology after ALND. Tumour size no larger than 20 mm, invasive ductal or lobular histology and breast conserving surgery were associated with the presence of two or fewer macrometastases at ALND. Only tumour size and tumour histology remained significant in multiple logistic regression analysis. CONCLUSION: Patients with AUS-detected metastases had a higher axillary tumour burden than those with SNB detected metastases. Around 40 per cent of patients with AUS-detected nodal disease had one or two nodes with macrometastases and were thus overtreated by ALND. PMID- 28991365 TI - Arterial stiffness, cognitive impairment and dementia: confounding factor or real risk? AB - Large artery stiffness is a frequent condition that arises with ageing, and is accelerated by the presence of co-morbidities like hypertension, obesity and diabetes. Although epidemiological studies have indicated an association between arterial stiffness, cognitive impairment and dementia, the precise effects of stiff arteries on the brain remains obscure. This is because, in humans, arterial stiffness is often accompanied by other factors such as age, high blood pressure, atherosclerosis and inflammation, which could themselves damage the brain independently of stiffness. Therefore, the question remains: is arterial stiffness a true risk for cognitive decline? Or, is it a confounding factor? In this review, we provide an overview of arterial stiffness and its impact on brain function based on human and animal studies. We summarize the evidence linking arterial stiffness to cognitive dysfunction and dementia, and discuss the role of new animal models to better understand the mechanisms by which arterial stiffness affects the brain. We close with an overview of treatments to correct stiffness and discuss the challenges to translate them to real patient care. This article is part of the Special Issue "Vascular Dementia". PMID- 28991363 TI - MicroRNA-495-3p functions as a tumor suppressor by regulating multiple epigenetic modifiers in gastric carcinogenesis. AB - MicroRNAs (miRNAs) engage in complex interactions with the machinery that controls the transcriptome and concurrently target multiple mRNAs. Here, we demonstrate that microRNA-495-3p (miR-495-3p) functions as a potent tumor suppressor by governing ten oncogenic epigenetic modifiers (EMs) in gastric carcinogenesis. From the large cohort transcriptome datasets of gastric cancer (GC) patients available from The Cancer Genome Atlas (TCGA) and the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO), we were able to recapitulate 15 EMs as significantly overexpressed in GC among the 51 EMs that were previously reported to be involved in cancer progression. Computational target prediction yielded miR-495-3p, which targets as many as ten of the 15 candidate oncogenic EMs. Ectopic expression of miRNA mimics in GC cells caused miR-495-3p to suppress ten EMs, and inhibited tumor cell growth and proliferation via caspase-dependent and caspase-independent cell death processing. In addition, in vitro metastasis assays showed that miR-495-3p plays a role in the metastatic behavior of GC cells by regulating SLUG, vimentin, and N cadherin. Furthermore, treatment of GC cells with 5-aza-2'-deoxcytidine restored miR-495-3p expression; sequence analysis revealed hypermethylation of the miR-495 3p promoter region in GC cells. A negative regulatory loop is proposed, whereby DNMT1, among ten oncogenic EMs, regulates miR-495-3p expression via hypermethylation of the miR-495-3p promoter. Our findings suggest that the functional loss or suppression of miR-495-3p triggers overexpression of multiple oncogenic EMs, and thereby contributes to malignant transformation and growth of gastric epithelial cells. Copyright (c) 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID- 28991366 TI - Regularity of a renewal process estimated from binary data. AB - Assessment of the regularity of a sequence of events over time is important for clinical decision-making as well as informing public health policy. Our motivating example involves determining the effect of an intervention on the regularity of HIV self-testing behavior among high-risk individuals when exact self-testing times are not recorded. Assuming that these unobserved testing times follow a renewal process, the goals of this work are to develop suitable methods for estimating its distributional parameters when only the presence or absence of at least one event per subject in each of several observation windows is recorded. We propose two approaches to estimation and inference: a likelihood based discrete survival model using only time to first event; and a potentially more efficient quasi-likelihood approach based on the forward recurrence time distribution using all available data. Regularity is quantified and estimated by the coefficient of variation (CV) of the interevent time distribution. Focusing on the gamma renewal process, where the shape parameter of the corresponding interevent time distribution has a monotone relationship with its CV, we conduct simulation studies to evaluate the performance of the proposed methods. We then apply them to our motivating example, concluding that the use of text message reminders significantly improves the regularity of self-testing, but not its frequency. A discussion on interesting directions for further research is provided. PMID- 28991367 TI - Elicitor and nitrogen applications to Garnacha, Graciano and Tempranillo vines: effect on grape amino acid composition. AB - BACKGROUND: Elicitors and nitrogen foliar applications to vineyards could regulate grape nitrogen composition, which has an important effect on grape and wine quality. Thus the aim of this research was to study the effect of foliar elicitor treatments, methyl jasmonate (MeJ) and yeast extract (YE), and foliar nitrogen applications, urea (Ur) and phenylalanine (Phe), to Garnacha, Graciano and Tempranillo vines on grape amino acid composition. RESULTS: The results showed that elicitor and nitrogen foliar applications to Garnacha and Tempranillo grapevines decreased the must amino acid concentration. However, Phe application to these two grapevines increased the must Phe content. The treatments applied to Graciano grapevines barely effected the grape amino acid content. According to the percentage of variance attributable, the variety had a higher impact on the must amino acid composition than the treatments and their interaction, except in certain amino acids such as Phe. CONCLUSION: The influence of elicitor and nitrogen foliar applications to grapevines on grape amino acid concentration was strongly conditioned by the variety. (c) 2017 Society of Chemical Industry. PMID- 28991368 TI - Predicting Discharge to Institutional Long-Term Care After Stroke: A Systematic Review and Metaanalysis. AB - BACKGROUND/OBJECTIVES: Stroke is a leading cause of disability worldwide, and a significant proportion of stroke survivors require long-term institutional care. Understanding who cannot be discharged home is important for health and social care planning. Our aim was to establish predictive factors for discharge to institutional care after hospitalization for stroke. DESIGN: We registered and conducted a systematic review and meta-analysis (PROSPERO: CRD42015023497) of observational studies. We searched MEDLINE, EMBASE, and CINAHL Plus to February 2017. Quantitative synthesis was performed where data allowed. SETTING: Acute and rehabilitation hospitals. PARTICIPANTS: Adults hospitalized for stroke who were newly admitted directly to long-term institutional care at the time of hospital discharge. MEASUREMENTS: Factors associated with new institutionalization. RESULTS: From 10,420 records, we included 18 studies (n = 32,139 participants). The studies were heterogeneous and conducted in Europe, North America, and East Asia. Eight studies were at high risk of selection bias. The proportion of those surviving to discharge who were newly discharged to long-term care varied from 7% to 39% (median 17%, interquartile range 12%), and the model of care received in the long-term care setting was not defined. Older age and greater stroke severity had a consistently positive association with the need for long-term care admission. Individuals who had a severe stroke were 26 times as likely to be admitted to long-term care than those who had a minor stroke. Individuals aged 65 and older had a risk of stroke that was three times as great as that of younger individuals. Potentially modifiable factors were rarely examined. CONCLUSION: Age and stroke severity are important predictors of institutional long-term care admission directly from the hospital after an acute stroke. Potentially modifiable factors should be the target of future research. Stroke outcome studies should report discharge destination, defining the model of care provided in the long-term care setting. PMID- 28991369 TI - Effects of late-stage nitrogen fertilizer application on the starch structure and cooking quality of rice. AB - BACKGROUND: With the rapid development of modern agriculture, high-quality rice production and consumption has become the current urgent demand for the development of rice production. In this paper, the effects of late-stage nitrogen fertilizer application on rice quality were studied under the same genetic background. Wx near-isogenic lines were used as test materials to study the starch composition, amylopectin structure and cooking quality of rice. RESULTS: Results showed that rice amylose content and gel consistency significantly differed when different Wx genes were tranformed into waxy rice. The law of apparent amylose content in rice is Wxa > Wxin > Wxb > wx at the same nitrogen level, while the trend of gel consistency was opposite to that of apparent amylose content, presenting obvious characteristics of Indica and Japonica varieties. As the amount of fertilizer application increased, apparent amylose content increased, gel consistency decreased, breakdown and peak viscosities dropped and setback viscosity and peak time increased. Moreover, the cooking quality of rice significantly decreased with the use of nitrogen fertilizer, especially under low-level nitrogen fertilizer application. Amylopectin structure varied significantly in different genotypes of the Wx gene, and the degree of branching was as follows: wx > Wxb > Wxin > Wxa . This result indicated that the closer to Indica rice, the fewer short chains of amylopectin. Starch crystallinity and swelling potential were negatively correlated with amylose content but significantly positively correlated with amylopectin branching degree, decreasing with the increase of late-stage nitrogen fertilization. CONCLUSION: Late-stage nitrogen fertilization reduced the cooking quality of rice by increasing amylose content and reducing amylopectin branching degree, which decreased starch crystallinity and aggravated pasting properties. Obviously, controlling late nitrogen application is essential to optimize rice quality. (c) 2017 Society of Chemical Industry. PMID- 28991370 TI - Ixekizumab treatment for psoriasis: integrated efficacy analysis of three double blinded, controlled studies (UNCOVER-1, UNCOVER-2, UNCOVER-3). AB - BACKGROUND: Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin (IL)-17A, is approved for the treatment of moderate-to-severe psoriasis. OBJECTIVES: This analysis represents an overview of the efficacy outcomes from three phase III psoriasis studies. METHODS: Data were integrated from the 12-week induction period of three studies in which patients received ixekizumab 80 mg every 2 weeks (IXE Q2W; n = 1169) or every 4 weeks (IXE Q4W; n = 1165) after an initial 160-mg dose for both; etanercept (50 mg biweekly; n = 740; two studies) or placebo (n = 792). The coprimary end points were the percentages of patients with response of static Physician's Global Assessment (sPGA; score 0 or 1) and >= 75% improvement in baseline Psoriasis Area and Severity Index (PASI 75) at week 12. Response rates were compared between treatments using the Cochran Mantel-Haenszel test stratified by study. Treatment comparisons with placebo included data from three studies, whereas etanercept comparisons were based on two studies. RESULTS: Ixekizumab treatment was superior to placebo (P < 0.001) and etanercept (P < 0.001) on sPGA (0, 1) and PASI 75, with significant differences in PASI improvement at week 1. With IXE Q2W, at week 12, the frequencies of patients achieving PASI 75, 90 and 100 were nearly 90%, 70% and 40%, respectively. Ixekizumab-treated patients showed significantly greater improvement vs. placebo and etanercept in percentage body surface area involvement and fingernail psoriasis. IXE Q2W was superior to IXE Q4W on all treatment outcomes. CONCLUSIONS: Ixekizumab therapy at both dosing regimens demonstrated rapid onset and superior efficacy to placebo and etanercept, with IXE Q2W providing better outcomes than IXE Q4W during the first 12 weeks of treatment. PMID- 28991371 TI - Protective effects of dietary polyphenols from black soybean seed coats on islet and renal function in streptozotocin-induced diabetic rats. AB - BACKGROUND: The aim of this study was to investigate the antidiabetic effects of the crude polyphenol extract (BSCP) from black soybean seed coats (BSC) and the whole flour of BSC and illustrate the mechanism in terms of islet and renal protection. RESULTS: BSCP and BSC effectively controlled the increased blood glucose level and impaired glucose tolerance in streptozotocin (STZ)-induced diabetic rats after 8 weeks of treatment. They increased the concentrations of serum insulin, C-peptide and Glp-1 (P < 0.05) by improving the STZ-induced damage of islet beta-cells and increasing their insulin expression (P < 0.05). Lipid profiles and antioxidant activities were also improved. Moreover, BSCP and BSC tended to decrease serum creatinine (0.05 < P < 0.1), and blood urea nitrogen was decreased by BSC significantly (P < 0.05). They also led to significantly lower glomerular volume (P < 0.05). CONCLUSION: Long-term intervention with BSC at a low dose of polyphenols plays a role in controlling blood glucose and lipids levels by promoting insulin secretion and restoring islet beta-cell function, the same as BSCP. These benefits are accompanied by their potential protection of diabetic renal dysfunction. BSCP is mainly responsible for the antidiabetic effect of BSC. (c) 2017 Society of Chemical Industry. PMID- 28991372 TI - No elevated risk for depression, anxiety or suicidality with secukinumab in a pooled analysis of data from 10 clinical studies in moderate-to-severe plaque psoriasis. PMID- 28991373 TI - Novel enriched pathways in superficial malignant peripheral nerve sheath tumours and spindle/desmoplastic melanomas. AB - Superficial malignant peripheral nerve sheath tumour (MPNST) is a rare, soft tissue neoplasm that shares morphological features and some molecular events with spindle/desmoplastic melanoma (SDM). Herein, we sought to identify molecular targets for therapy by using targeted RNA/DNA sequencing and gene expression of key immunological players. DNA and RNA from formalin-fixed paraffin-embedded tissue were extracted and processed. Massive high-throughput deep parallel sequencing was performed with the Oncomine comprehensive panel, enabling detection of relevant single-nucleotide variants, copy number variations, gene fusions and indels for 143 unique genes on the Ion torrent sequencer for clinical trial research programmes. Gene expression analysis was carried out with a customized 770-gene expression panel combining markers for 24 different immune cell types and 30 common cancer antigens, including key checkpoint blockade genes analysed with the Ncounter system. Fifty-one patients (SDM, 16/11; MPNST, 24; male, n = 37; female, n = 16) had sufficient DNA and RNA for testing. NF1 deleterious mutations and/or deep/homozygous deletions were identified in 73% of MPNSTs and 67% of SDMs, with 50% of the mutations involving the RAS-binding domain. Inactivating/deleterious mutations of TSC1/TSC2 were identified in 40% and 41% of MPNSTs and SDMs, respectively. Activating mutations affecting the EGFR like and the negative regulatory domains of NOTCH1 and KDR (VEGFR2) were identified in 45% and 40% of SDMs and in 30% and 8% of MPNSTs, respectively. Differential gene expression and gene clustering analysis showed significantly perturbed immune pathway components, including nuclear factor-kappaB (NF-kappaB), JAK-STAT, and CXCL12-CXCR4, and differentially expressed CD274 and CTLA4, in both SDM and MPNST. Angiogenesis (KDR and NOTCH1) and mammalian target of rapamycin complex (mTORC) pathways offer a rationale for anti-angiogenic and selective mTORC inhibition as treatment strategies for MPNST and SDM. Cytokines and the JAK STAT, TNF and NF-kappaB axes were perturbed in both SDM and MPNST. These pathways have been targeted in haematological malignancies and present promising targets for these tumours. Copyright (c) 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID- 28991374 TI - Synaptopodin-2 suppresses metastasis of triple-negative breast cancer via inhibition of YAP/TAZ activity. AB - Triple-negative breast cancer (TNBC) represents the most aggressive subtype of breast cancer, with a high incidence of distant metastasis; however, the underlying mechanism for this frequent recurrence remains unclear. Herein, we show that synaptopodin-2 (SYNPO2), a putative tumour suppressor in aggressive cancer, is frequently downregulated in TNBC by methylation of the promoter of SYNPO2. Low expression levels of SYNPO2 correlated significantly with 5-year metastatic relapse, and predicted poorer prognosis in breast cancer patients. Reintroduction of SYNPO2 inhibited the invasion and spontaneous metastasis of TNBC cells in vivo. Strikingly, downregulation of SYNPO2 is essential for the maintenance of stem cell-like properties in TNBC cells, leading to efficient distant colonization and metastasis outgrowth. Moreover, we demonstrate that SYNPO2 inhibits the activities of YAP and TAZ by stabilizing LATS2 protein, and transduction of YAP-S127A abrogates the repressive role of SYNPO2 in metastasis. Finally, immunohistochemical (IHC) analysis of breast cancer patient specimens indicated that the SYNPO2-LATS2-YAP axis is clinically relevant. These findings uncover a suppressive role of SYNPO2 in TNBC metastasis via inhibition of YAP/TAZ, and suggest that SYNPO2 might provide a potential prognosis marker and novel therapeutic strategy. Copyright (c) 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID- 28991375 TI - A GLM-based latent variable ordination method for microbiome samples. AB - Distance-based ordination methods, such as principal coordinates analysis (PCoA), are widely used in the analysis of microbiome data. However, these methods are prone to pose a potential risk of misinterpretation about the compositional difference in samples across different populations if there is a difference in dispersion effects. Accounting for high sparsity and overdispersion of microbiome data, we propose a GLM-based Ordination Method for Microbiome Samples (GOMMS) in this article. This method uses a zero-inflated quasi-Poisson (ZIQP) latent factor model. An EM algorithm based on the quasi-likelihood is developed to estimate parameters. It performs comparatively to the distance-based approach when dispersion effects are negligible and consistently better when dispersion effects are strong, where the distance-based approach sometimes yields undesirable results. The estimated latent factors from GOMMS can be used to associate the microbiome community with covariates or outcomes using the standard multivariate tests, which can be investigated in future confirmatory experiments. We illustrate the method in simulations and an analysis of microbiome samples from nasopharynx and oropharynx. PMID- 28991376 TI - Sugar metabolism and developmental stages of rubber tree (Hevea brasiliensis L.) seeds. AB - Changes in the concentration of sugars and sucrose metabolism enzymes can characterize the developmental stages of a seed. In recalcitrant species such as Hevea brasiliensis L., little is known about these changes. We aimed to evaluate the three main stages of development of rubber tree seeds - histodifferentiation, cell elongation and accumulation of reserves. The activities of acid and neutral invertases (E.C. 3.2.1.26) and sucrose synthase (EC 2.4.1.13), and the concentrations of reducing sugars (RS), total soluble sugars (TSS) and sucrose (Suc) were determined concomitantly with the histochemical and anatomical evaluation of seed structure. Histodifferentiation in rubber tree seeds occurs up to 75 days after anthesis (DAA). The concentration of RS is high and of Suc is low during seed histodifferentiation, which occurs along with a visible increase in the number of cell divisions. After that period, there is an increase in the concentration of Suc (mg g-1 ) and in the number and size of starch granules, and a decrease in the concentration of RS (mg g-1 ). At that point, cell elongation occurs. At 135 DAA, there is an inversion in the concentration of these two sugars and an increase in reserve accumulation. Thus, in seeds of the evaluated clone, the period up to 75 DAA is characterized as the histodifferentiation stage, while from that time up to 120 DAA the cell elongation stage takes place. The final stage of seed maturation and reserve accumulation begins at 135 DAA, and the seed, including the embryo, is completely formed at 175 DAA. PMID- 28991377 TI - EBSD investigation of Al/(Al13 Fe4 +Al2 O3 ) nanocomposites fabricated by mechanical milling and friction stir processing. AB - The application of ball-milling for reactant powders (Fe2 O3 +Al) to form in situ nanosized reaction products in the stir zone of 1050 aluminium alloy was examined and the evolution of microstructure, grain boundaries and microtexture of the fabricated Al/(Al13 Fe4 +Al2 O3 ) nanocomposite was investigated. The mean matrix grain size of the fabricated nanocomposites by the combination of ball milling and friction stir processing were found to be ~3.2, 3.1 and 2.1 MUm for 1, 2 and 3 h milled powder mixtures, respectively. The fraction of high-angle grain boundaries increased markedly in the stir zone indicating the occurrence of dynamic restoration of the aluminium matrix. This was also associated with increasing of the fraction of low ?CSL boundaries. In addition, the fraction of high-angle grain boundaries increased as the reaction product increased. The developed textures were compared with the most important deformation and recrystallisation texture components of cubic close packed structure. Some of the main texture components formed due to the restoration of aluminium in the stir zone of the material with no powder addition were CubeND {001}<310>, BR {236}<385> and R (or retained S{123} <634>); these are usually found in the rolled materials. However, the presence of nanosized reaction products in the fabricated nanocomposite changed the texture components to the dominant Goss {011}<100>, P {011}<122> and R{124}<211> textures. PMID- 28991378 TI - Accuracy and safety of pin placement during lateral versus dorsal stabilization of lumbar spinal fracture-luxation in dogs. AB - OBJECTIVE: To determine the accuracy and safety of pin placement for lateral vertebral stabilization to the reference dorsal stabilization. STUDY DESIGN: A randomized noninferiority trial. SAMPLE POPULATION: Twenty Greyhound cadaveric lumbar spines (L1-L6). METHODS: One hundred and fifty-nine lumbar vertebral pins placed in 80 vertebrae were assessed; these pins were distributed approximately equally between the dorsal and lateral approaches, and between 2 surgeons. Pin angle accuracy, bone purchase distance, and distances from pin to the spinal canal and the aorta were measured for each pin. RESULTS: The lateral approach was superior for pin angle accuracy and bone purchase. The mean angle of deviation was 15.3 degrees with the dorsal approach and 7.0 degrees with the lateral approach. The mean bone purchase was 16.7 mm with the dorsal approach and 22.2 mm with the lateral approach. Pins were placed at a mean of 2.3 mm from the spinal canal with the dorsal approach and 1.7 mm with the lateral approach. Pins were placed at a mean of 3.8 mm from the aorta with the dorsal approach and 8.0 mm with the lateral approach. The percentage of pins breaching the spinal canal was 14% with the dorsal approach and 19% with the lateral approach. Fourteen percent of pins placed via the dorsal approach breached the aorta, whereas no pins placed via the lateral approach breached the aorta. CONCLUSION: Relative to the dorsal approach, the lateral approach improves angle accuracy, bone purchase, and distance between pins, and the aorta and is noninferior with regards to the distance between pins and the spinal canal. PMID- 28991379 TI - A target and nontarget strategy for identification or characterization of the chemical ingredients in Chinese herb preparation Shuang-Huang-Lian oral liquid by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. AB - A target and nontarget strategy based on in-house chemical components library was developed for rapid and comprehensive analysis of complicated components from traditional Chinese medicine preparation Shuang-Huang-Lian oral liquid. The sample was analyzed by ultra-performance liquid chromatography-quadrupole time-of flight mass spectrometry using generic acquisition parameters. Automated detection and data filtering were performed on the UNIFITM software and the detected peaks were evaluated against an in-house library. As a result, a total of 170 chemical components (110 target compounds and 60 nontarget ones) were identified or tentatively characterized, including 54 flavonoids, 30 phenylethanoid glycosides, 16 iridoid glycosides, 14 lignans, 32 organic acids, 19 triterpenoid saponins and five other types of compounds. Among them, 44 compounds were further confirmed by comparison with reference standards. It was demonstrated that this systematical approach could be successfully applied for rapid identification of multiple compounds in traditional Chinese medicine and its preparations. Furthermore, this work established the foundation for the further investigation on the metabolic fates of multiple ingredients in Shuang Huang-Lian oral liquid. PMID- 28991380 TI - Dental microwear textural analysis as an analytical tool to depict individual traits and reconstruct the diet of a primate. AB - OBJECTIVES: Dental microwear is a promising tool to reconstruct animals' diet because it reflects the interplay between the enamel surface and the food items recently consumed. This study examines the sources of inter-individual variations in dietary habits in a free-ranging population of mandrills (Mandrillus sphinx) using a combination of feeding monitoring and in vivo dental microwear textural analysis (DMTA). METHODS: We investigated the impact of seasonality and individual traits on four DMTA parameters. In parallel, we further studied the influence of the physical properties of the food items consumed on these four parameters, using three proxies (mechanical properties, estimates of phytolith and external grit contents). RESULTS: We found that seasonality, age, and sex all impact DMTA parameters but those results differ depending on the facet analyzed (crushing vs. shearing facets). Three DMTA parameters (anisotropy, complexity, and heterogeneity of complexity) appear sensitive to seasonal variations and anisotropy also differs between the sexes while textural fill volume tends to vary with age. Moreover, the physical properties of the food items consumed vary seasonally and also differ depending on individual sex and age. CONCLUSION: Considering the interplay between the tested variables and both dental microwear and diet, we reaffirm that food physical properties play a major role in microwear variations. These results suggest that DMTA parameters may provide valuable hints for paleoecological reconstruction using fragmentary fossil dental remains. PMID- 28991381 TI - Rational In Silico Design of an Organic Semiconductor with Improved Electron Mobility. AB - Organic semiconductors find a wide range of applications, such as in organic light emitting diodes, organic solar cells, and organic field effect transistors. One of their most striking disadvantages in comparison to crystalline inorganic semiconductors is their low charge-carrier mobility, which manifests itself in major device constraints such as limited photoactive layer thicknesses. Trial-and error attempts to increase charge-carrier mobility are impeded by the complex interplay of the molecular and electronic structure of the material with its morphology. Here, the viability of a multiscale simulation approach to rationally design materials with improved electron mobility is demonstrated. Starting from one of the most widely used electron conducting materials (Alq3 ), novel organic semiconductors with tailored electronic properties are designed for which an improvement of the electron mobility by three orders of magnitude is predicted and experimentally confirmed. PMID- 28991382 TI - Chemistry and Biology of Teixobactin. AB - Bacterial resistance to existing drugs is becoming a serious public health issue, urging extensive search for new antibiotics. Teixobactin, a cyclic depsipeptide discovered in a screen of uncultured bacteria, shows potent activity against all the tested Gram-positive bacteria. Remarkably, no teixobactin-resistant bacterial strain has been obtained despite extensive efforts, highlighting the great potential of teixobactin as a lead compound in the fight against antimicrobial resistance (AMR). This review summarizes recent progresses in the understanding of many aspects of teixobactin, including chemical structure, biological activity, biosynthetic pathway, and mode of action. We also discuss the different synthetic strategies in producing teixobactin and its analogues, and the structure-activity relationship (SAR) studies. PMID- 28991383 TI - Realization of Large Electric Polarization and Strong Magnetoelectric Coupling in BiMn3 Cr4 O12. AB - Magnetoelectric multiferroics have received much attention in the past decade due to their interesting physics and promising multifunctional performance. For practical applications, simultaneous large ferroelectric polarization and strong magnetoelectric coupling are preferred. However, these two properties have not been found to be compatible in the single-phase multiferroic materials discovered as yet. Here, it is shown that superior multiferroic properties exist in the A site ordered perovskite BiMn3 Cr4 O12 synthesized under high-pressure and high temperature conditions. The compound experiences a ferroelectric phase transition ascribed to the 6s2 lone-pair effects of Bi3+ at around 135 K, and a long-range antiferromagnetic order related to the Cr3+ spins around 125 K, leading to the presence of a type-I multiferroic phase with huge electric polarization. On further cooling to 48 K, a type-II multiferroic phase induced by the special spin structure composed of both Mn- and Cr-sublattices emerges, accompanied by considerable magnetoelectric coupling. BiMn3 Cr4 O12 thus provides a rare example of joint multiferroicity, where two different types of multiferroic phases develop subsequently so that both large polarization and significant magnetoelectric effect are achieved in a single-phase multiferroic material. PMID- 28991384 TI - High-Performance Flexible Photodetectors based on High-Quality Perovskite Thin Films by a Vapor-Solution Method. AB - Organometal halide perovskites are new light-harvesting materials for lightweight and flexible optoelectronic devices due to their excellent optoelectronic properties and low-temperature process capability. However, the preparation of high-quality perovskite films on flexible substrates has still been a great challenge to date. Here, a novel vapor-solution method is developed to achieve uniform and pinhole-free organometal halide perovskite films on flexible indium tin oxide/poly(ethylene terephthalate) substrates. Based on the as-prepared high quality perovskite thin films, high-performance flexible photodetectors (PDs) are constructed, which display a nR value of 81 A W-1 at a low working voltage of 1 V, three orders higher than that of previously reported flexible perovskite thin film PDs. In addition, these flexible PDs exhibit excellent flexural stability and durability under various bending situations with their optoelectronic performance well retained. This breakthrough on the growth of high-quality perovskite thin films opens up a new avenue to develop high-performance flexible optoelectronic devices. PMID- 28991385 TI - An Ultrastable and High-Performance Flexible Fiber-Shaped Ni-Zn Battery based on a Ni-NiO Heterostructured Nanosheet Cathode. AB - Currently, the main bottleneck for the widespread application of Ni-Zn batteries is their poor cycling stability as a result of the irreversibility of the Ni based cathode and dendrite formation of the Zn anode during the charging discharging processes. Herein, a highly rechargeable, flexible, fiber-shaped Ni Zn battery with impressive electrochemical performance is rationally demonstrated by employing Ni-NiO heterostructured nanosheets as the cathode. Benefiting from the improved conductivity and enhanced electroactivity of the Ni-NiO heterojunction nanosheet cathode, the as-fabricated fiber-shaped Ni-NiO//Zn battery displays high capacity and admirable rate capability. More importantly, this Ni-NiO//Zn battery shows unprecedented cyclic durability both in aqueous (96.6% capacity retention after 10 000 cycles) and polymer (almost no capacity attenuation after 10 000 cycles at 22.2 A g-1 ) electrolytes. Moreover, a peak energy density of 6.6 uWh cm-2 , together with a remarkable power density of 20.2 mW cm-2 , is achieved by the flexible quasi-solid-state fiber-shaped Ni-NiO//Zn battery, outperforming most reported fiber-shaped energy-storage devices. Such a novel concept of a fiber-shaped Ni-Zn battery with impressive stability will greatly enrich the flexible energy-storage technologies for future portable/wearable electronic applications. PMID- 28991386 TI - Enhanced Open-Circuit Voltage in Colloidal Quantum Dot Photovoltaics via Reactivity-Controlled Solution-Phase Ligand Exchange. AB - The energy disorder that arises from colloidal quantum dot (CQD) polydispersity limits the open-circuit voltage (VOC ) and efficiency of CQD photovoltaics. This energy broadening is significantly deteriorated today during CQD ligand exchange and film assembly. Here, a new solution-phase ligand exchange that, via judicious incorporation of reactivity-engineered additives, provides improved monodispersity in final CQD films is reported. It has been found that increasing the concentration of the less reactive species prevents CQD fusion and etching. As a result, CQD solar cells with a VOC of 0.7 V (vs 0.61 V for the control) for CQD films with exciton peak at 1.28 eV and a power conversion efficiency of 10.9% (vs 10.1% for the control) is achieved. PMID- 28991387 TI - Soft tissue rheology and its implications for elastography: Challenges and opportunities. AB - Magnetic resonance elastography and related shear wave ultrasound elastography techniques can be used to estimate the mechanical properties of soft tissues in vivo by using the relationships between wave propagation and the elastic properties of materials. These techniques have found numerous clinical and research applications, tracking changes in tissue properties as a result of disease or other interventions. Most dynamic elastography approaches estimate tissue elastic (or viscoelastic) properties from a simplified version of the equations for the propagation of acoustic waves through a homogeneous linear (visco)elastic medium. However, soft tissue rheology is complex and departs significantly from this idealized picture. In particular, soft tissues are nonlinearly viscoelastic, inhomogeneous and often anisotropic, and their apparent stiffness can vary with the current loading state. All of these features have implications for the reliability and reproducibility of elastography measurements, from data acquisition to analysis and interpretation. New developments in inversion algorithms for elastography are beginning to offer solutions to account for the complex rheology of tissues, including inhomogeneity and anisotropy. There remains considerable potential to further refine elastography to capture the full spectrum of tissue rheology, and thus to better understand the underlying tissue microstructural changes in a broad range of clinical disorders. PMID- 28991388 TI - Specific optical rotation is a versatile tool for the identification of critical micelle concentration and micellar growth of tartaric acid-based diastereomeric amphiphiles. AB - Four novel tartaric acid-based diastereomeric chiral amphiphiles, two being enantiomers of the other two, have been synthesized and investigated using chiroptical spectroscopic methods, along with tensiometry and dynamic light scattering experiments. We found that an inflection point in specific optical rotation (SOR) values at ~0.32 mM corresponds to the critical micelle concentration (CMC). The increase in magnitude of SOR values beyond CMC corresponds to the growth of aggregates. For enantiomers, oppositely signed SOR values were observed, ruling out the possibility for the presence of aggregation size mediated artefacts. SOR values did not exhibit concentration dependence for a chiral tartaric acid based non-aggregating analogue further establishing the absence of artefacts or anomalous interaction of tartaric acid based head group with solvent. Electronic circular dichroism spectra showed no significant changes in band positions or intensities with concentration. Due to the requirement for higher concentrations (~200 mM) needed to obtain vibrational circular dichroism spectra, these measurements are not found to be useful for studying concentration dependent properties of chiral amphiphiles. PMID- 28991389 TI - Peroxidase-Mimicking Nanozyme with Enhanced Activity and High Stability Based on Metal-Support Interactions. AB - Peroxidase-mimicking nanozymes offer unique advantages in terms of high stability and low cost over natural peroxidase for applications in bioanalysis, biomedicine, and the treatment of pollution. However, the design of high efficiency peroxidase-mimicking nanozymes remains a great challenge. In this study, we adopted a structural-design approach through hybridization of cube-CeO2 and Pt nanoparticles to create a new peroxidase-mimicking nanozyme with high efficiency and excellent stability. Relative to pure cube-CeO2 and Pt nanoparticles, the as-hybridized Pt/cube-CeO2 nanocomposites display much improved activities because of the strong metal-support interaction. Meanwhile, the nanocomposites also maintain high catalytic activity after long-term storage and multiple recycling. Based on their excellent properties, Pt/cube-CeO2 nanocomposites were used to construct high-performance colorimetric biosensors for the sensitive detection of metabolites, including H2 O2 and glucose. Our findings highlight opportunities for the development of high-efficiency peroxidase-mimicking nanozymes with potential applications such as diagnostics, biomedicine, and the treatment of pollution. PMID- 28991390 TI - Magnetically Controlled Growth-Factor-Immobilized Multilayer Cell Sheets for Complex Tissue Regeneration. AB - The scaffold-free cell-sheet technique plays a significant role in stem-cell based regeneration. Furthermore, growth factors are known to direct stem cell differentiation and enhance tissue regeneration. However, the absence of an effective means to incorporate growth factors into the cell sheets hinders further optimization of the regeneration efficiency. Here, a novel design of magnetically controlled "growth-factor-immobilized cell sheets" is reported. A new Fe3 O4 magnetic nanoparticle (MNP) coated with nanoscale graphene oxide (nGO@Fe3 O4 ) is developed to label stem cells and deliver growth factors. First, the nGO@Fe3 O4 MNPs can be easily swallowed by dental-pulp stem cells (DPSCs) and have no influence on cell viability. Thus, the MNP-labeled cells can be organized via magnetic force to form multilayered cell sheets in different patterns. Second, compared to traditional Fe3 O4 nanoparticles, the graphene oxide coating provides plenty of carboxyl groups to bind and deliver growth factors. Therefore, with these nGO@Fe3 O4 MNPs, bone-morphogenetic-protein-2 (BMP2) is successfully incorporated into the DPSCs sheets to induce more bone formation. Furthermore, an integrated osteochondral complex is also constructed using a combination of DPSCs/TGFbeta3 and DPSCs/BMP2. All these results demonstrate that the new cell sheet tissue-engineering approach exhibits promising potential for future use in regenerative medicine. PMID- 28991391 TI - Evaluation of reticulocyte hemoglobin content (RET-He) in the diagnosis of iron deficient erythropoiesis in dogs. AB - BACKGROUND: Reticulocyte hemoglobin content provided by the Siemens ADVIA (CHr) is an established marker of iron deficiency. The IDEXX ProCyte Dx hematology analyzer now provides a similar variable, reticulocyte hemoglobin equivalent (RET He). OBJECTIVES: The objective was to evaluate RET-He and its diagnostic utility in dogs, and to calculate a cutoff value for diagnosing iron-deficient erythropoiesis (IDE). Furthermore, the prevalence of RET-He values below this cutoff value was established. METHODS: One hundred and seventy-one CBCs of healthy dogs were used to establish a RI. Stability of RET-He was evaluated by repeated measurements over 48 hours (n = 10). The 25-run coefficient of variation (CV) was calculated, and correlation and bias between measurements of RET-He and CHr were assessed (n = 190). A cutoff value for diagnosing IDE was calculated. The utility of RET-He in the detection of IDE was evaluated in 123 dogs. The prevalence of low RET-He values was assessed retrospectively in a multicenter study (2012-2014) under participation of 7 veterinary clinics. RESULTS: Reticulocyte hemoglobin equivalent with an RI of 22.2 to 28.6 pg was statistically stable over 48 hours (P = .10). The CV was 1.8%. A fair correlation (rho = 0.74) between RET-He and CHr with a small bias of -0.6 pg was found. The cutoff value for diagnosing IDE was 20.9 pg (sensitivity: 85%; specificity: 99%). The prevalence of RET-He values below 20.9 pg was 10.3% (1084/10,553 dogs). CONCLUSIONS: RET-He on the ProCyte Dx is a precise screening tool in dogs to detect iron-deficient erythropoiesis. PMID- 28991392 TI - Ambireactive (R3 P)2 BH2 Groups Facilitating Temperature-Switchable Bond Activation by an Iron Complex. AB - An iron pincer complex containing a hemi-labile (R3 P)2 BH2 group exhibits temperature-switchable reactivity patterns: a reversible B-H activation concomitant with a P-B bond cleavage is observed at room temperature. Below 4 degrees C, intra- and intermolecular C-H activation pathways are becoming faster and more dominant. Mechanistic investigations reveal that the lability of the (R3 P)2 BH2 group in combination with the exothermic formation of sigma-bonded complexes are responsible for the switchable bond activation. Finally, a protocol for an iron-catalyzed H/D-exchange of organic solvents in the absence of oxidants has been developed. PMID- 28991393 TI - Screening of analgesic and anti-inflammatory active component in Fructus Alpiniae zerumbet based on spectrum-effect relationship and GC-MS. AB - Fructus Alpiniae zerumbet is widely used in Guizhou province as a miao folk herb with anti-inflammatory, analgesic, protection against cardiovascular diseases, antihypertension and antioxidant activities. To further investigate the chemical material basis, the spectrum-effect relationship was established using gray relational analysis between the chromatographic fingerprint and its bioactivities. Herein, the fingerprints of essential oils from Fructus Alpiniae zerumbet (EOFAZ) from various sources were determined by gas chromatography mass spectrometry, and the analgesic and anti-inflammatory bioactivities were investigated using the mouse model of acetic acid-induced writhing test and dimethylbenzene-induced mouse ear edema test. Finally, 17 common peaks were identified from nine batches of A. zerumbet, by comparison with the standard mass spectra in Nist2005, Wiley275 library. Meanwhile, the results showed significant analgesic and anti-inflammatory effects in all of the different sources of EOFAZ. In particularly, peak 1 (alpha-pipene), peak 3 (beta-pinene), peak 9 (camphor) and peak 16 (alpha-cadinol) might be the main bioactive ingredients for analgesic and anti-inflammatory activities. The model of the spectrum-effect relationships of EOFAZ was successfully discovered, which provided a novel platform for finding the bioactive components, a theoretical foundation for its further study and helping to establish quality control of Fructus A. zerumbet. PMID- 28991394 TI - Wrinkled 2D Materials: A Versatile Platform for Low-Threshold Stretchable Random Lasers. AB - A stretchable, flexible, and bendable random laser system capable of lasing in a wide range of spectrum will have many potential applications in next- generation technologies, such as visible-spectrum communication, superbright solid-state lighting, biomedical studies, fluorescence, etc. However, producing an appropriate cavity for such a wide spectral range remains a challenge owing to the rigidity of the resonator for the generation of coherent loops. 2D materials with wrinkled structures exhibit superior advantages of high stretchability and a suitable matrix for photon trapping in between the hill and valley geometries compared to their flat counterparts. Here, the intriguing functionalities of wrinkled reduced graphene oxide, single-layer graphene, and few-layer hexagonal boron nitride, respectively, are utilized to design highly stretchable and wearable random laser devices with ultralow threshold. Using methyl-ammonium lead bromide perovskite nanocrystals (PNC) to illustrate the working principle, the lasing threshold is found to be ~10 uJ cm-2 , about two times less than the lowest value ever reported. In addition to PNC, it is demonstrated that the output lasing wavelength can be tuned using different active materials such as semiconductor quantum dots. Thus, this study is very useful for the future development of high-performance wearable optoelectronic devices. PMID- 28991395 TI - Failures and long-term discontinuations of intradetrusor botulinum toxin injections for neurogenic detrusor overactivity: A new challenge in neurourology. PMID- 28991396 TI - [(CH3 )3 NH]3 Bi2 I9 : A Polar Lead-Free Hybrid Perovskite-Like Material as a Potential Semiconducting Absorber. AB - Perovskite hybrids of lead organometal halides, most notably CH3 NH3 PbI3 , have shown extremely promising applications in the field of optoelectronics, because of their remarkable semiconducting and light-absorbing properties. However, two key issues-the toxicity of lead and the poor ambient instabilities-have restrained their further commercialization. Herein, we have designed a new stable polar lead-free hybrid material by utilizing the strategy of cation substitution, [(CH3 )3 N]3 Bi2 I9 (1), which adopts the 0D inorganic perovskite-like architecture by face-sharing BiI6 octahedra. It is interesting that 1 displays excellent absorbing properties with a narrow optical band gap of ~2.0 eV, and positive temperature-dependent conductivity confirms its semiconducting behaviors. In addition, 1 has good phase stability against decomposition under ambient conditions, much superior to that of CH3 NH3 PbI3 . This work suggests the potential of 1 as a lead-free semiconducting absorber with high phase stability for photoelectric applications. PMID- 28991398 TI - In Situ TEM Studies of Nanostructured Thermoelectric Materials: An Application to Mg-Doped Zn4 Sb3 Alloy. AB - We demonstrate an advanced approach using state of the art in situ transmission electron microscopy (TEM) to understand the interplay between nanostructures and thermoelectric (TE) properties of high-performance Mg-doped Zn4 Sb3 TE systems. By using the technique, microstructure and crystal evolutions of TE material have been dynamically captured as a function of temperature from 300 K to 573 K. On heating, we have clearly observed precipitation and growth of a Zn-rich secondary phase as nanoinclusions in the matrix of primary Zn4 Sb3 phase. Elemental mapping by STEM-EDX spectroscopy reveals enrichment of Zn in the secondary Zn6 Sb5 nanoinclusions during the thermal processing without decomposition. Such nanostructures strongly enhances phonon scattering, resulting in a decrease in the thermal conductivity leading to a zT value of 1.4 at 718 K. PMID- 28991397 TI - Record linkage study of the pathogen-specific burden of respiratory viruses in children. AB - BACKGROUND: Reliance on hospital discharge diagnosis codes alone will likely underestimate the burden of respiratory viruses. OBJECTIVES: To describe the epidemiology of respiratory viruses more accurately, we used record linkage to examine data relating to all children hospitalized in Western Australia between 2000 and 2012. PATIENTS/METHODS: We extracted hospital, infectious disease notification and laboratory data of a cohort of children born in Western Australia between 1996 and 2012. Laboratory records of respiratory specimens collected within 48 hours of admission were linked to hospitalization records. We calculated the frequency and rates of virus detection. To identify groups where under-ascertainment for respiratory viruses was greatest, we used logistic regression to determine factors associated with failure to test. RESULTS AND CONCLUSIONS: Nine percentage of 484 992 admissions linked to a laboratory record for respiratory virus testing. While 62% (n = 26 893) of laboratory-confirmed admissions received respiratory infection diagnosis codes, 38% (n = 16 734) had other diagnoses, notably viral infection of unspecified sites. Of those tested, incidence rates were highest for respiratory syncytial virus (247 per 100 000 child-years) followed by parainfluenza (63 per 100 000 child-years). Admissions among older children and those without a respiratory diagnosis were associated with failure to test for respiratory viruses. Linked data can significantly enhance diagnostic codes when estimating the true burden of disease. In contrast to current emphasis on influenza, respiratory syncytial virus and parainfluenza were the most common viral pathogens among hospitalized children. By characterizing those failing to be tested, we can begin to quantify the under ascertainment of respiratory viruses. PMID- 28991399 TI - Soil carbon cycling proxies: Understanding their critical role in predicting climate change feedbacks. AB - The complexity of processes and interactions that drive soil C dynamics necessitate the use of proxy variables to represent soil characteristics that cannot be directly measured (correlative proxies), or that aggregate information about multiple soil characteristics into one variable (integrative proxies). These proxies have proven useful for understanding the soil C cycle, which is highly variable in both space and time, and are now being used to make predictions of the fate and persistence of C under future climate scenarios. However, the C pools and processes that proxies represent must be thoughtfully considered in order to minimize uncertainties in empirical understanding. This is necessary to capture the full value of a proxy in model parameters and in model outcomes. Here, we provide specific examples of proxy variables that could improve decision-making, and modeling skill, while also encouraging continued work on their mechanistic underpinnings. We explore the use of three common soil proxies used to study soil C cycling: metabolic quotient, clay content, and physical fractionation. We also consider how emerging data types, such as genome sequence data, can serve as proxies for microbial community activities. By examining some broad assumptions in soil C cycling with the proxies already in use, we can develop new hypotheses and specify criteria for new and needed proxies. PMID- 28991400 TI - Resistance to cycloxaprid in Laodelphax striatellus is associated with altered expression of nicotinic acetylcholine receptor subunits. AB - BACKGROUND: Cycloxaprid is a new oxabridged cis-configuration neonicotinoid insecticide, the resistance development potential and underlying resistance mechanism of which were investigated in the small brown planthopper, Laodelphax striatellus (Fallen), an important agricultural pest of rice. RESULTS: A cycloxaprid-resistant strain (YN-CPD) only achieved 10-fold higher resistance, in contrast to 106-fold higher resistance to buprofezin and 332-fold higher resistance to chlorpyrifos achieved after exposure to similar selection pressure, and the cycloxaprid selected line showed no cross-resistance to the buprofezin and chlorpyrifos-selected resistance strains. Moreover, we identified 10 nicotinic acetylcholine receptor (nAChR) subunits from the transcriptome of L. striatellus, and six segments had open reading frames (ORFs). While we did not find mutations in the nAChR genes of L. striatellus, subunits Lsalpha1 and Lsbeta1 exhibited, respectively, 9.60-fold and 3.36-fold higher expression in the resistant strain, while Lsalpha8 exhibited 0.44-fold lower expression. Suppression of Lsalpha1 through ingestion of dsLsalpha1 led to an increase in susceptibility to cycloxaprid. CONCLUSION: The findings indicate that resistance to cycloxaprid develops slowly compared with resistance to other chemicals and without cross-resistance to chlorpyrifos or buprofezin; over-expressed Lsalpha1 is associated with low cycloxaprid resistance levels, but the importance of over expressed Lsbeta1 and reduced expression of Lsalpha8 could not be excluded. (c) 2017 Society of Chemical Industry. PMID- 28991401 TI - Recent Trends in Baccalaureate-Prepared Registered Nurses in U.S. Acute Care Hospital Units, 2004-2013: A Longitudinal Study. AB - PURPOSE: To examine the trends in baccalaureate (bachelor of science in nursing) prepared registered nurses (BSN RNs) in U.S. acute care hospital units and to project the growth in the number of BSN RNs by 2020. DESIGN: This is a longitudinal study using the Registered Nurse Education Indicators data (2004 2013) from the National Database of Nursing Quality Indicators. METHODS: The level of BSN RNs in each unit was operationalized as the proportion of nurses holding a baccalaureate degree or higher among all the nurses in a unit. Our sample included 12,194 unit-years from 2,126 units of six cohorts in 377 U.S. acute care hospitals. A hierarchical linear regression model was used to examine the trends in BSN RNs and to project future growth in the number of BSN RNs when controlling for hospital and unit characteristics and considering repeated measures in units over time and clustering of units within hospitals. RESULTS: The proportion of BSN RNs in U.S. acute care hospital units increased from 44% in 2004 to 57% in 2013 (a 30% increase); when combining all cohorts, this rate increased from 44% in 2009 to 51% in 2013. On average, the proportion of BSN RNs in a unit increased by 1.3% annually before 2010 and by 1.9% each year from 2010 on. The percentage of units having at least 80% of their nurses with a baccalaureate degree or higher increased from 3% in 2009 to 7% in 2013. Based on the current trends, 64% of the nurses working in a hospital unit will have a baccalaureate degree by 2020, and 22% of the units will reach the 80% goal by 2020. CONCLUSIONS: There was a significant increase in the proportion of BSN RNs in U.S. acute care hospital units over the past decade, particularly after 2010. However, given the current trends, it is unlikely that the goal of 80% nurses with a baccalaureate degree will be achieved by 2020. CLINICAL RELEVANCE: The U.S. nursing workforce is under educational transformation in order to meet the increasing healthcare needs. To help accelerate this transformation, further advocacy, commitment, and investment are needed from all healthcare stakeholders (e.g., policymakers, executives and managers of healthcare facilities, nursing schools, etc.). PMID- 28991402 TI - Self-Powered Nanoscale Photodetectors. AB - Novel self-powered nanoscale photodetectors that can work without an external power source, which have great application potential in next-generation nanodevices that operate wirelessly and independently, are being widely studied. This review aims to give a comprehensive summary of the state-of-the-art research results on self-powered nanoscale photodetectors. An introduction of recent progress on Schottky junction photodetectors is provided. Two types of Schottky junctions are discussed in detail: metal-semiconductor and semiconductor-graphene junctions. Next, recent developments of p-n junction photodetectors are highlighted, including homojunction and heterojunction photodetectors. Then, piezo-phototronic effect enhanced photodetection performances of Schottky junctions and p-n junctions are discussed. Then, significant results on the photoelectrochemical-cell-based photodetector and integrated self-powered nanosystem are presented, followed by a systematic comparison of different types of photodetectors. Finally, a summary of the previous results is given, and the major challenges that need to be addressed in the future are outlined. The hope is that this review can provide valuable insights into the current status of self powered photodetectors and spur new structure and device designs to further enhance photodetection performance. PMID- 28991403 TI - Breaking the Limits in Analyzing Carbohydrate Recognition by NMR Spectroscopy: Resolving Branch-Selective Interaction of a Tetra-Antennary N-Glycan with Lectins. AB - The biological recognition of complex-type N-glycans is part of many key physiological and pathological events. Despite their importance, the structural characterization of these events remains unsolved. The inherent flexibility of N glycans hampers crystallization and the chemical equivalence of individual branches precludes their NMR characterization. By using a chemoenzymatically synthesized tetra-antennary N-glycan conjugated to a lanthanide binding tag, the NMR signals under paramagnetic conditions discriminated all four N-acetyl lactosamine antennae with unprecedented resolution. The NMR data revealed the conformation of the N-glycan and permitted for the first time the direct identification of individual branches involved in the recognition by two N acetyllactosamine-binding lectins, Datura stramonium seed lectin (DSL) and Ricinus Communis agglutinin (RCA120). PMID- 28991405 TI - Improving models of photosynthetic thermal acclimation: Which parameters are most important and how many should be modified? AB - Photosynthetic temperature acclimation could strongly affect coupled vegetation atmosphere feedbacks in the global carbon cycle, especially as the climate warms. Thermal acclimation of photosynthesis can be modelled as changes in the parameters describing the direct effect of temperature on photosynthetic capacity (i.e., activation energy, Ea ; deactivation energy, Hd ; entropy parameter, DeltaS) or the basal value of photosynthetic capacity (i.e., photosynthetic capacity measured at 25 degrees C). However, the impact of acclimating these parameters (individually or in combination) on vegetative carbon gain is relatively unexplored. Here we compare the ability of 66 photosynthetic temperature acclimation scenarios to improve the ability of a spatially explicit canopy carbon flux model, MAESTRA, to predict eddy covariance data from a loblolly pine forest. We show that: (1) incorporating seasonal temperature acclimation of basal photosynthetic capacity improves the model's ability to capture seasonal changes in carbon fluxes and outperforms acclimation of other single factors (i.e., Ea or DeltaS alone); (2) multifactor scenarios of photosynthetic temperature acclimation provide minimal (if any) improvement in model performance over single factor acclimation scenarios; (3) acclimation of Ea should be restricted to the temperature ranges of the data from which the equations are derived; and (4) model performance is strongly affected by the Hd parameter. We suggest that a renewed effort be made into understanding whether basal photosynthetic capacity, Ea , Hd and DeltaS co-acclimate across broad temperature ranges to determine whether and how multifactor thermal acclimation of photosynthesis occurs. PMID- 28991404 TI - Rapid changes in serum cytokines and chemokines in response to inactivated influenza vaccination. AB - BACKGROUND: The timing of host cytokine responses to influenza vaccination is poorly understood. OBJECTIVES: We examined serum cytokine kinetics following inactivated trivalent influenza vaccine (TIV) to better understand potential relationships between markers of inflammation and TIV-related side effects. PATIENTS/METHODS: Twenty healthy adult subjects received TIV. Cytokines/chemokines were assessed in intervals from 3 hours to 14 days. Antibody titers were measured at baseline and Day 14. RESULTS: Serum cytokine responses to TIV were evident as early as 3 hours post-immunization. Compared to baseline, IFN gamma and IP-10 were significantly elevated 7 hours after TIV administration. Both remained elevated and peaked between 16 and 24 hours before returning to baseline by 44 hours post-vaccination. Although IL-8 levels were variable between subjects during the first 24 hours after TIV, by 44 hours, IL-8 was significantly lower compared to baseline. Interestingly, IL-8 levels remained significantly lower for up to 2 weeks after receiving TIV. Fifteen of 20 subjects reported mild adverse events. The one subject who reported moderate myalgias and injection site pain after vaccination displayed a distinctive, early cytokine response profile which included IL-6, IL-2, IL-8, IP-10, MCP-1, TNF-alpha, TARC, and MCP-4. CONCLUSIONS: Serum cytokines changed rapidly following TIV and generally peaked at 24 hours. Trivalent influenza vaccine-induced reductions in IL-8 occurred later (44 hours) and were sustained for 2 weeks. An outlier response coincided with the only moderate side effects to the vaccine. These data suggest that early cytokine/chemokine responses may provide additional insight into the pathogenesis of adverse events and immune reactivity to vaccination. PMID- 28991407 TI - Hydrogen Peroxide Insular Dodecameric and Pentameric Clusters in Peroxosolvate Structures. AB - Peroxosolvates of 2-aminonicotinic acid (I) and lidocaine N-oxide (II) including the largest insular hydrogen peroxide clusters were isolated and their crystal structures were determined by single-crystal X-ray diffraction. An unprecedented dodecameric hydrogen peroxide insular cluster was found in I. An unusual cross like pentameric cluster was observed in the structure of II. The topology of the (H2 O2 )12 assembly was never observed for small-molecule clusters. In I and II new double and triple cross-orientational disorders of H2 O2 were found. Cluster II is the first example of a peroxosolvate crystal structure containing H2 O2 molecules with a homoleptic hydrogen peroxide environment. In II, a hydrogen bond between an H2 O2 molecule and a peptide group -CONH???O2 H2 was observed for the first time. PMID- 28991406 TI - Burden of influenza among hospitalized febrile children in Ghana. AB - BACKGROUND: Influenza surveillance data from Africa indicate a substantial disease burden with high mortality. However, local influenza data from district hospitals with limited laboratory facilities are still scarce. OBJECTIVES: To identify the frequency and seasonal distribution of influenza among hospitalized febrile children in a rural hospital in Ghana and to describe differential diagnoses to other severe febrile infections. METHODS: Between January 2014 and April 2015, all children with a temperature of >=38 degrees C admitted to a district hospital in Ghana were screened for influenza A and B by RT-PCR and differentiated to subtypes A(H1N1)pdm09 and A(H3N2). Malaria microscopy and blood cultures were performed for each patient. RESULTS: A total of 1063 children with a median age of 2 years (IQR: 1-4 years) were recruited. Of those, 271 (21%) were classified as severe acute respiratory infection (SARI) and 47 (4%) were positive for influenza, namely 26 (55%) influenza B, 15 (32%) A(H1N1)pdm09, and 6 (13%) A(H3N2) cases. Influenza predominantly occurred in children aged 3-5 years and was more frequently detected in the major rainy season (OR = 2.9; 95% CI: 1.47 6.19) during the first half of the year. Two (4%) and seven (15%) influenza positive children were co-diagnosed with an invasive bloodstream infection or malaria, respectively. CONCLUSION: Influenza contributes substantially to the burden of hospitalized febrile children in Ghana being strongly dependent on age and corresponds with the major rainy season during the first half-year. PMID- 28991408 TI - Tipping point in plant-fungal interactions under severe drought causes abrupt rise in peatland ecosystem respiration. AB - Ecosystems are increasingly prone to climate extremes, such as drought, with long lasting effects on both plant and soil communities and, subsequently, on carbon (C) cycling. However, recent studies underlined the strong variability in ecosystem's response to droughts, raising the issue of nonlinear responses in plant and soil communities. The conundrum is what causes ecosystems to shift in response to drought. Here, we investigated the response of plant and soil fungi to drought of different intensities using a water table gradient in peatlands-a major C sink ecosystem. Using moving window structural equation models, we show that substantial changes in ecosystem respiration, plant and soil fungal communities occurred when the water level fell below a tipping point of -24 cm. As a corollary, ecosystem respiration was the greatest when graminoids and saprotrophic fungi became prevalent as a response to the extreme drought. Graminoids indirectly influenced fungal functional composition and soil enzyme activities through their direct effect on dissolved organic matter quality, while saprotrophic fungi directly influenced soil enzyme activities. In turn, increasing enzyme activities promoted ecosystem respiration. We show that functional transitions in ecosystem respiration critically depend on the degree of response of graminoids and saprotrophic fungi to drought. Our results represent a major advance in understanding the nonlinear nature of ecosystem properties to drought and pave the way towards a truly mechanistic understanding of the effects of drought on ecosystem processes. PMID- 28991409 TI - Effects of seasonal and pandemic influenza on health-related quality of life, work and school absence in England: Results from the Flu Watch cohort study. AB - BACKGROUND: Estimates of health-related quality of life (HRQoL) and work/school absences for influenza are typically based on medically attended cases or those meeting influenza-like-illness (ILI) case definitions and thus biased towards severe disease. Although community influenza cases are more common, estimates of their effects on HRQoL and absences are limited. OBJECTIVES: To measure quality adjusted life days and years (QALDs and QALYs) lost and work/school absences among community cases of acute respiratory infections (ARI), ILI and influenza A and B and to estimate community burden of QALY loss and absences from influenza. PATIENTS/METHODS: Flu Watch was a community cohort in England from 2006 to 2011. Participants were followed up weekly. During respiratory illness, they prospectively recorded daily symptoms, work/school absences and EQ-5D-3L data and submitted nasal swabs for RT-PCR influenza testing. RESULTS: Average QALD lost was 0.26, 0.93, 1.61 and 1.84 for ARI, ILI, H1N1pdm09 and influenza B cases, respectively. 40% of influenza A cases and 24% of influenza B cases took time off work/school with an average duration of 3.6 and 2.4 days, respectively. In England, community influenza cases lost 24 300 QALYs in 2010/11 and had an estimated 2.9 million absences per season based on data from 2006/07 to 2009/10. CONCLUSIONS: Our QALDs and QALYs lost and work and school absence estimates are lower than previous estimates because we focus on community cases, most of which are mild, may not meet ILI definitions and do not result in healthcare consultations. Nevertheless, they contribute a substantial loss of HRQoL on a population level. PMID- 28991410 TI - How much does climate change threaten European forest tree species distributions? AB - Although numerous species distribution models have been developed, most were based on insufficient distribution data or used older climate change scenarios. We aimed to quantify changes in projected ranges and threat level by the years 2061-2080, for 12 European forest tree species under three climate change scenarios. We combined tree distribution data from the Global Biodiversity Information Facility, EUFORGEN, and forest inventories, and we developed species distribution models using MaxEnt and 19 bioclimatic variables. Models were developed for three climate change scenarios-optimistic (RCP2.6), moderate (RCP4.5), and pessimistic (RPC8.5)-using three General Circulation Models, for the period 2061-2080. Our study revealed different responses of tree species to projected climate change. The species may be divided into three groups: "winners" mostly late-successional species: Abies alba, Fagus sylvatica, Fraxinus excelsior, Quercus robur, and Quercus petraea; "losers"-mostly pioneer species: Betula pendula, Larix decidua, Picea abies, and Pinus sylvestris; and alien species-Pseudotsuga menziesii, Quercus rubra, and Robinia pseudoacacia, which may be also considered as "winners." Assuming limited migration, most of the species studied would face a significant decrease in suitable habitat area. The threat level was highest for species that currently have the northernmost distribution centers. Ecological consequences of the projected range contractions would be serious for both forest management and nature conservation. PMID- 28991411 TI - Structural insights into the nuclear import of the histone acetyltransferase males-absent-on-the-first by importin alpha1. AB - The histone acetyltransferase males-absent-on-the-first (MOF) acetylates the histone H4, a modification important for many biological processes, including chromatin organization, transcriptional regulation, DNA replication, recombination and repair, as well as autophagy. Depletion of MOF induces serious consequences because of the reduction of histone acetylation, such as nuclear morphological defects and cancer. Despite the critical roles of MOF in the nucleus, the structural or functional mechanisms of the nucleocytoplasmic transport of MOF remain elusive. Here, we identified novel importin alpha1 specific nuclear localization signals (NLSs) in the N-terminal of human MOF. The crystal structure of MOF NLSs in complex with importin alpha1 further revealed a unique binding mode of MOF, with two independent NLSs binding to importin alpha1 major and minor sites, respectively. The second NLS of MOF displays an unexpected alpha-helical conformation in the C-terminus, with more extensive contacts with importin alpha1 not limited in the minor site. Mutations of the key residues on MOF and importin alpha1 lead to the reduction of their interaction as well as the nuclear import of MOF, revealing an essential role of NLS2 of MOF in interacting with importin alpha1 minor site. Taken together, we provide structural mechanisms underlying the nucleocytoplasmic transport of MOF, which will be of great importance in understanding the functional regulation of MOF in various biological processes. PMID- 28991412 TI - Virtual Screening Approach of Bacterial Peptide Deformylase Inhibitors Results in New Antibiotics. AB - The increasing resistance of bacteria to antibacterial therapy poses an enormous health problem, it renders the development of new antibacterial agents with novel mechanism of action an urgent need. Peptide deformylase, a metalloenzyme which catalytically removes N-formyl group from N-terminal methionine of newly synthesized polypeptides, is an important target in antibacterial drug discovery. In this study, we report the structure-based virtual screening of ZINC database in order to discover potential hits as bacterial peptide deformylase enzyme inhibitors with more affinity as compared to GSK1322322, previously known inhibitor. After virtual screening, fifteen compounds of the top hits predicted were purchased and evaluated in vitro for their antibacterial activities against one Gram positive (Staphylococcus aureus) and three Gram negative (Escherichia coli, Pseudomonas aeruginosa and Klebsiella. pneumoniae) bacteria in different concentrations by disc diffusion method. Out of these, three compounds, ZINC00039650, ZINC03872971 and ZINC00126407, exhibited significant zone of inhibition. The results obtained were confirmed using the dilution method. Thus, these proposed compounds may aid the development of more efficient antibacterial agents. PMID- 28991413 TI - Ligand-based Modeling for the Prediction of Pharmacophore Features for Multi targeted Inhibition of the Arachidonic Acid Cascade. AB - The single-target drugs against the arachidonic acid inflammatory pathway are associated with serious side effects, hence, as a first step towards multi-target drugs, we have studied the pharmacophoric features common to the inhibitors of 5 lipoxygenase-activating protein (FLAP), microsomal prostaglandin E-synthase 1 (mPGES-1) and leukotriene A4 hydrolase (LTA4H). FLAP and mPGES-1 shared subfamily specific positions (SSPs) and four mPGES-1 inhibitors binding to them mapped onto the pharmacophore derived from FLAP inhibitors (Ph-FLAP). The reactions of mPGES 1 and LTA4H had high structural similarity. The pharmacophore derived from two substrate mimic inhibitors of LTA4H (Ph-LTA4H) also mapped onto three mPGES-1 inhibitors. Screening of in-house database for Ph-FLAP and Ph-LTA4H identified one compound, C1. It inhibited the production of the mPGES-1 product, prostaglandin E2 (PGE2) by 97.8+/-1.6 % at 50 MUM in HeLa cells and can be a starting point for designing molecules inhibiting all three targets simultaneously. PMID- 28991414 TI - In Situ Spatial Complementation of Aptamer-Mediated Recognition Enables Live-Cell Imaging of Native RNA Transcripts in Real Time. AB - Direct cellular imaging of the localization and dynamics of biomolecules helps to understand their function and reveals novel mechanisms at the single-cell resolution. In contrast to routine fluorescent-protein-based protein imaging, technology for RNA imaging remains less well explored because of the lack of enabling technology. Herein, we report the development of an aptamer-initiated fluorescence complementation (AiFC) method for RNA imaging by engineering a green fluorescence protein (GFP)-mimicking turn-on RNA aptamer, Broccoli, into two split fragments that could tandemly bind to target mRNA. When genetically encoded in cells, endogenous mRNA molecules recruited Split-Broccoli and brought the two fragments into spatial proximity, which formed a fluorophore-binding site in situ and turned on fluorescence. Significantly, we demonstrated the use of AiFC for high-contrast and real-time imaging of endogenous RNA molecules in living mammalian cells. We envision wide application and practical utility of this enabling technology to in vivo single-cell visualization and mechanistic analysis of macromolecular interactions. PMID- 28991415 TI - Refractive error, through the lens of the patient. PMID- 28991416 TI - Differences in bleb morphology between trabeculectomy and deep sclerectomy. PMID- 28991417 TI - Continuing Professional Development. PMID- 28991418 TI - Agrochemical lead optimization by scaffold hopping. AB - Scaffold hopping, the exchange of a specific portion of a potential active ingredient with another substructure with the aim of finding isofunctional molecular structures with significantly different molecular backbones, often offers the chance in lead discovery or optimization to mitigate problems related to toxicity, intellectual property, and insufficient potency or stability. Scaffold hopping tools such as isosteric ring replacement including 1,3 nitrogen shift and cyclic imine-amide isosterism, but also ring opening and ring closure approaches, functional group isosterism, reversion of functional groups, chain shortening, chain lengthening, and scaffolds delivered by natural products, have become a permanent fixture of the innovation and optimization process in crop protection research. Their appropriate use will be explained through examples of success stories in the field of agrochemistry. Analogies to, but also differences from, the main categories of scaffold hopping in medicinal drug discovery are discussed. (c) 2017 Society of Chemical Industry. PMID- 28991419 TI - Synergistic interactions between a variety of insecticides and an ergosterol biosynthesis inhibitor fungicide in dietary exposures of bumble bees (Bombus terrestris L.). AB - BACKGROUND: In recent years, concern has been raised over honey bee colony losses, and also among wild bees there is evidence for extinctions and range contractions in Europe and North America. Pesticides have been proposed as a potential cause of this decline. Bees are exposed simultaneously to a variety of agrochemicals, which may cause synergistically detrimental impacts, which are incompletely understood. We investigated the toxicity of the fungicide imazalil in mixture with four common insecticides: fipronil (phenylpyrazoid), cypermethrin (pyrethroid), thiamethoxam, and imidacloprid (neonicotinoids). Ergosterol biosynthesis inhibitor (EBI) fungicides like imazalil can inhibit P450 detoxification systems in insects and therefore fungicide - insecticide co occurrence might produce synergistic toxicity in bees. We assessed the impact of dietary fungicide - insecticide mixtures on the mortality and feeding rates of laboratory bumble bees (Bombus terrestris L.). RESULTS: Regarding mortality, imazalil synergised the toxicity of fipronil, cypermethrin and thiamethoxam, but not imidacloprid. We found no synergistic effects on feeding rates. CONCLUSION: Our findings suggest that P450-based detoxification processes are differentially important in mitigating the toxicity of certain insecticides, even those of the same chemical class. Our evidence that cocktail effects can arise in bumble bees should extend concern about the potential impacts of agrochemical mixtures to include wild bee species in farmland. (c) 2017 Society of Chemical Industry. PMID- 28991421 TI - Worth the Wait? The Effect of Early Term Birth on Maternal and Infant Health. AB - Early term birth is defined as birth at 37 or 38 weeks gestation. While infants born early term are not considered premature, the medical literature suggests that they have an increased risk of serious adverse health outcomes compared to infants born at term (39 or 40 weeks). Despite these known harms, we document a rise in early term births in the United States from 1989 to the mid-2000s, followed by a decline in recent years. We posit that the recent decline in early term births has been driven by changes in medical practice advocated by the American College of Obstetricians and Gynecologists, programs such as the March of Dimes' "Worth the Wait" campaign, and by Medicaid policy. We first show that this pattern cannot be attributed to changes in the demographic composition of mothers, and provide some evidence that efforts to reduce early term elective deliveries (EEDs) through Medicaid policy were effective. Wenext exploit county level variation in the timing of these changes in medical practice to examine the effect of early term inductions (our proxy for EEDs) on infant and maternal health. We find that early term inductions lower birth weights and increase the risks of precipitous labor, birth injury, and required ventilation. Our results suggest that reductions in early term inductions can explain about one-third of the overall increase in birth weights between 2010 and 2013 for births at 37 weeks gestation and above. PMID- 28991422 TI - Emission Standards, Public Transit, and Infant Health. AB - Transit buses are an integral part of urban life. They reduce externalities generated from private vehicles and increase geographic mobility. However, unlike most private vehicles in the United States, they use diesel fuel and emit higher amounts of toxic pollutants. The U.S. Environmental Protection Agency set emission standards for transit buses starting in 1988 that have been continually updated, but their public health and economic impacts are unclear due to scarce emissions data. I construct a novel panel dataset for the New York City (NYC) Transit bus fleet between 1990 and 2009 and examine the impact of bus pollution on infant health by using bus vintage as a proxy for emissions. I exploit the variation in vintage as older buses are retired and replaced with newer, lower emitting buses forced to adhere to stricter emission standards. I then assign maternal exposure to bus vintage at the census block level. Findings suggest that maternal exposure to the oldest, unregulated buses is associated with modest reductions in birth weight and gestational age relative to newer buses that abide by emissions policies. I then conduct a back-of-the-envelope cost-benefit calculation and find net economic benefits of $53.3 million resulting from improved emission standards for the 2009 birth cohort in NYC. Since the treatment in this study clearly maps to federal emissions policies, these results are the first to provide credible evidence that transit bus emission standards had a positive effect on infant health. PMID- 28991423 TI - Child Health in Elementary School Following California's Paid Family Leave Program. AB - We evaluate changes in elementary school children health outcomes following the introduction of California's Paid Family Leave (PFL) program, which provided parents with paid time off following the birth of a child. Our health outcomes- overweight, ADHD, and hearing-related problems--are characterized by diagnosis rates that only pick up during early elementary school. Moreover, our health outcomes have been found to be negatively linked with many potential implications of extended maternity leave--increased breastfeeding, prompt medical checkups at infancy, reduced prenatal stress, and reduced non-parental care during infancy. Using the Early Childhood Longitudinal Studies (ECLS) within a difference-in differences framework, our results suggest improvements in health outcomes among California elementary school children following PFL's introduction. Furthermore, the improvements are driven by children from less advantaged backgrounds, which is consistent with the notion that California's PFL had the greatest effect on leave-taking duration after childbirth mostly for less advantaged mothers who previously could not afford to take unpaid leave. PMID- 28991424 TI - Do Higher Minimum Wages Benefit Health? Evidence From the UK. AB - This study examines the link between minimum wages and health outcomes by using the introduction of the National Minimum Wage (NMW) in the United Kingdom in 1999 as an exogenous variation of earned income. A test for health effects by using longitudinal data from the British Household Panel Survey for a period of ten years was conducted. It was found that the NMW significantly improved several measures of health, including self-reported health status and the presence of health conditions. When examining potential mechanisms, it was shown that changes in health behaviors, leisure expenditures, and financial stress can explain the observed improvements in health. PMID- 28991425 TI - The Economic Impact of Smoke-Free Policies on Restaurants, Cafes, and Bars: Panel Data Estimates From European Countries. AB - In this paper, we investigate the extent to which the economic outcomes of restaurants, bars, and cafes have been affected by the introduction of anti smoking regulations in Europe. We use an unexploited panel database to collect a comprehensive set of information on financial indicators regarding the balance sheets of private and public companies in various economic sectors. The results show that smoke-free policies did not significantly affect the firms' economic performance, irrespective of the balance sheet indicators analyzed. Moreover, the results are robust to various econometric specifications and suggest that the recent enforcement of anti-smoking legislation in Europe has improved public health without a corresponding negative impact on revenuesand employment in the hospitality industry. PMID- 28991426 TI - Scraping by: Income and Program Participation After the Loss of Extended Unemployment Benefits. AB - Many Unemployment Insurance (UI) recipients do not find new jobs before exhausting their benefits, even when benefits are extended during recessions. Using Survey of Income and Program Participation (SIPP) panel data covering the 2001 and 2007 to 2009 recessions and their aftermaths, we identify individuals whose jobless spells outlasted their UI benefits (exhaustees) and examine household income, program participation, and health-related outcomes during the six months following UI exhaustion. For the average exhaustee, the loss of UI benefits is only slightly offset by increased participation in other safety net programs (e.g., food stamps), and family poverty rates rise substantially. Self reported disability also rises following UI exhaustion. These patterns do not vary dramatically across household demographic groups, broad income level prior to job loss, or the two business cycles. The results highlight the unique, important role of UI in the U.S. social safety net. PMID- 28991427 TI - Molecular Engineering of Platinum(II) Terpyridine Complexes with Tetraphenylethylene-Modified Alkynyl Ligands: Supramolecular Assembly via Pt...Pt and/or pi-pi Stacking Interactions and the Formation of Various Superstructures. AB - A series of platinum(II) terpyridine complexes with tetraphenylethylene-modified alkynyl ligands has been designed and synthesized. The introduction of the tetraphenylethylene motif has led to aggregation-induced emission (AIE) properties, which upon self-assembly led to the formation of metal-metal-to ligand charge transfer (MMLCT) behavior stabilized by Pt...Pt and/or pi-pi interactions. Tuning the steric bulk or hydrophilicity through molecular engineering of the platinum(II) complexes has been found to alter their spectroscopic properties and result in interesting superstructures (including nanorods, nanospheres, nanowires, and nanoleaves) in the self-assembly process. The eye-catching color and emission changes upon varying the solvent compositions may have potential applications in chemosensing materials for the detection of microenvironment changes. Furthermore, the importance of the directional Pt...Pt and/or pi-pi interactions on the construction of distinctive superstructures has also been examined by UV-vis absorption and emission spectroscopy and transmission electron microscopy. This work represents the interplay of both inter- and intramolecular interactions as well as the energies of the two different chromophoric/luminophoric systems that may open up a new route for the development of platinum(II)-AIE hybrids as functional materials. PMID- 28991429 TI - Drastically Enhancing Moduli of Graphene-Coated Carbon Nanotube Aerogels via Densification while Retaining Temperature-Invariant Superelasticity and Ultrahigh Efficiency. AB - Lightweight open-cell foams that are simultaneously superelastic, possess exceptionally high Young's moduli (Y), exhibit ultrahigh efficiency, and resist fatigue as well as creep are particularly desirable as structural frameworks. Unfortunately, many of these features are orthogonal in foams of metals, ceramics, and polymers, particularly under large temperature variations. In contrast, foams of carbon allotropes including carbon nanotubes and graphene developed over the past few years exhibit these desired properties but have low Y due to low density, rho = 0.5-10 mg/mL. Densification of these foams enhances Y although below expectation and also dramatically degrades other properties because of drastic changes in microstructure. We have recently developed size- and shape-tunable graphene-coated single-walled carbon nanotube (SWCNT) aerogels that display superelasticity at least up to a compressive strain (epsilon) = 80%, fatigue and creep resistance, and ultrahigh efficiency over -100-500 degrees C. Unfortunately, Y of these aerogels is only ~0.75 MPa due to low rho ~ 14 mg/mL, limiting their competitiveness as structural foams. We report fabrication of similar aerogels but with rho spanning more than an order of magnitude from 16 400 mg/mL through controlled isostatic compression in the presence of a polymer coating circumventing any microstructural changes in stark contrast to other foams of carbon allotropes. The compressive stress (sigma) versus epsilon measurements show that the densification of aerogels from rho ~ 16 to 400 mg/mL dramatically enhances Y from 0.9 to 400 MPa while maintaining superelasticity at least up to epsilon = 10% even at the highest rho. The storage (E') and loss (E") moduli measured in the linear regime show ultralow loss coefficient, tan delta = E"/E' ~ 0.02, that remains constant over three decades of frequencies (0.628-628 rad/s), suggesting unusually high frequency-invariant efficiency. Furthermore, these aerogels retain exceptional fatigue resistance for 106 loading-unloading cycles to epsilon = 2% and creep resistance for at least 30 min under sigma = 0.02 MPa with rho = 16 mg/mL and sigma = 2.5 MPa with higher rho = 400 mg/mL. Lastly, these robust mechanical properties are stable over a broad temperature range of -100-500 degrees C, motivating their use as highly efficient structural components in environments with extreme temperature variations. PMID- 28991428 TI - Discovery of a Selective Allosteric Inhibitor Targeting Macrodomain 2 of Polyadenosine-Diphosphate-Ribose Polymerase 14. AB - Macrodomains are conserved protein interaction modules that can be found in all domains of life including in certain viruses. Macrodomains mediate recognition of sequence motifs harboring adenosine diphosphate ribose (ADPR) modifications, thereby regulating a variety of cellular processes. Due to their role in cancer or viral pathogenesis, macrodomains have emerged as potential therapeutic targets, but the unavailability of small molecule inhibitors has hampered target validation studies so far. Here, we describe an efficient screening strategy for identification of small molecule inhibitors that displace ADPR from macrodomains. We report the discovery and characterization of a macrodomain inhibitor, GeA-69, selectively targeting macrodomain 2 (MD2) of PARP14 with low micromolar affinity. Co-crystallization of a GeA-69 analogue with PARP14 MD2 revealed an allosteric binding mechanism explaining its selectivity over other human macrodomains. We show that GeA-69 engages PARP14 MD2 in intact cells and prevents its localization to sites of DNA damage. PMID- 28991430 TI - Charge Transfer in Ultrafine LDH Nanosheets/Graphene Interface with Superior Capacitive Energy Storage Performance. AB - Two-dimensional LDH nanosheets recently have generated considerable interest in various promising applications because of their intriguing properties. Herein, we report a facile in situ nucleation strategy toward in situ decorating monodispersed Ni-Fe LDH ultrafine nanosheets (UNs) on graphene oxide template based on the precise control and manipulation of LDH UNs anchored, nucleated, grown, and crystallized. Anion-exchange behavior was observed in this Ni-Fe LDH UNs@rGO composite. The Ni-Fe LDH UNs@rGO electrodes displayed a significantly enhanced specific capacitance (2715F g-1 at 3 A g-1) and energy density (82.3 Wh kg-1 at 661 W kg-1), which exceeds the energy densities of most previously reported nickel iron oxide/hydroxides. Moreover, the asymmetric supercapacitor, with the Ni-Fe LDH UNs @rGO composite as the positive electrode material and reduced graphene oxide (rGO) as the negative electrode material, exhibited a high energy density (120 Wh kg -1) at an average power density of 1.3 kW kg -1. A charge transfer from LDH layer to graphene layer, which means a built in electric field directed from LDH to graphene can be established by DFT calculations, which can significantly accelerate reaction kinetics and effectively optimize the capacitive energy storage performance. PMID- 28991431 TI - Steric-Hindrance-Functionalized Polydiarylfluorenes: Conformational Behavior, Stabilized Blue Electroluminescence, and Efficient Amplified Spontaneous Emission. AB - Control of the hierarchical molecular organization of polydiarylfluorenes by synthetic strategies is significant for optimizing photophysical properties as well as the performance of light-emitting devices. Herein, for the suppression of molecular aggregation and enhancement of luminescence efficiency, a series of steric units were introduced into polydiarylfluorenes by copolymerization, with the aim of integrating the advantages of the steric-hindrance effect and of the beta-phase. Optical and Raman spectroscopies revealed a beta-phase conformation for a polymer copolymerized with spiro[fluorene-9,9'-xanthene] (SFX), with photoluminescence (PL) peaks at 454, 482, and 517 nm. Moreover, the morphological stability and electroluminescence (EL) stability were also improved without compromising the performance of the polymer light-emitting diodes (PLEDs). Furthermore, three steric-hindrance-functionalized copolymers showed significantly decreased thresholds for amplified spontaneous emission (EthASE) and enhanced stability following thermal annealing treatment. These results indicate that steric-hindrance functionalization is a superior approach to improve the overall stability and optoelectronic properties for blue-light emitting pi-conjugated polymers. PMID- 28991432 TI - One-Pot Synthesis of Reduced Graphene Oxide/Metal (Oxide) Composites. AB - Graphene, one of the most attractive two-dimensional nanomaterials, has demonstrated a broad range of applications because of its excellent electronic, mechanical, optical, and chemical properties. In this work, a general, environmentally friendly, one-pot method for the fabrication of reduced graphene oxide (RGO)/metal (oxide) (e.g., RGO/Au, RGO/Cu2O, and RGO/Ag) composties was developed using glucose as the reducing agent and the stabilizer. The glucose not only reduced GO effectively to RGO but also reduced the metal precursors to form metal (oxide) nanoparticles on the surface of RGO. Moreover, the RGO/metal (oxide) composites were stabilized by gluconic acid on the surface of RGO. The developed RGO/metal (oxide) composites were characterized using STEM, FE-SEM, EDS, UV-vis absorption spectroscopy, XRD, FT-IR, and Raman spectroscopy. Finally, the developed nanomaterials were successfully applied as an electrode catalyst to simultaneous electrochemical analysis of l-ascorbic acid, dopamine, and uric acid. PMID- 28991433 TI - Selective Targeting of Vibrios by Fluorescent Siderophore-Based Probes. AB - Siderophores are small molecules used to specifically transport iron into bacteria via related receptors. By adapting siderophores and hijacking their pathways, we may discover an efficient and selective way to target microbes. Herein, we report the synthesis of a siderophore-fluorophore conjugate VF-FL derived from vibrioferrin (VF). Using flow cytometry and fluorescence microscopy, the probe selectively labeled vibrios, including V. parahaemolyticus, V. cholerae, and V. vulnificus, even in the presence of other species such as S. aureus and E. coli. The labeling is siderophore-related and both iron-limited conditions and the siderophore moiety are required. The competitive relationship between VF-FL and VF in vibrios implies an unreported VF-related transport mechanism in V. cholerae and V. vulnificus. These studies demonstrate that the siderophore scaffold provides a method to selectively target microbes expressing cognate receptors under iron-limited conditions. PMID- 28991434 TI - Biomimetic, Strong, Tough, and Self-Healing Composites Using Universal Sealant Loaded, Porous Building Blocks. AB - Many natural materials, such as nacre and dentin, exhibit multifunctional mechanical properties via structural interplay between compliant and stiff constituents arranged in a particular architecture. Herein, we present, for the first time, the bottom-up synthesis and design of strong, tough, and self-healing composite using simple but universal spherical building blocks. Our composite system is composed of calcium silicate porous nanoparticles with unprecedented monodispersity over particle size, particle shape, and pore size, which facilitate effective loading and unloading with organic sealants, resulting in 258% and 307% increases in the indentation hardness and elastic modulus of the compacted composite. Furthermore, heating the damaged composite triggers the controlled release of the nanoconfined sealant into the surrounding area, enabling moderate recovery in strength and toughness. This work paves the path towards fabricating a novel class of biomimetic composites using low-cost spherical building blocks, potentially impacting bone-tissue engineering, insulation, refractory and constructions materials, and ceramic matrix composites. PMID- 28991435 TI - Space-Confined Earth-Abundant Bifunctional Electrocatalyst for High-Efficiency Water Splitting. AB - Hydrogen generation from water splitting could be an alternative way to meet increasing energy demands while also balancing the impact of energy being supplied by fossil-based fuels. The efficacy of water splitting strongly depends on the performance of electrocatalysts. Herein, we report a unique space-confined earth-abundant electrocatalyst having the bifunctionality of simultaneous hydrogen evolution reaction (HER) and oxygen evolution reaction (OER), leading to high-efficiency water splitting. Outperforming Pt/C or RuO2 catalysts, this mesoscopic, space-confined, bifunctional configuration is constructed from a monolithic zeolitic imidazolate framework@layered double hydroxide (ZIF@LDH) precursor on Ni foam. Such a confinement leads to a high dispersion of ultrafine Co3O4 nanoparticles within the N-doped carbon matrix by temperature-dependent calcination of the ZIF@LDH. We demonstrate that the OER has an overpotential of 318 mV at a current density of 10 mA cm-2, while that of HER is -106 mV @ -10 mA cm-2. The voltage applied to a two-electrode cell for overall water splitting is 1.59 V to achieve a stable current density of 10 mA cm-2 while using the monolithic catalyst as both the anode and the cathode. It is anticipated that our space-confined method, which focuses on earth-abundant elements with structural integrity, may provide a novel and economically sound strategy for practical energy conversion applications. PMID- 28991436 TI - Aptamer-Modified Tetrahedral DNA Nanostructure for Tumor-Targeted Drug Delivery. AB - Tetrahedral DNA nanostructures (TDNs) are considered promising drug delivery carriers because they are able to permeate cellular membrane and are biocompatible and biodegradable. Furthermore, they can be modified by functional groups. To improve the drug-delivering ability of TDNs, we chose anticancer aptamer AS1411 to modify TDNs for tumor-targeted drug delivery. AS1411 can specifically bind to nucleolin, which is overexpressed on the cell membrane of tumor cells. Furthermore, AS1411 can inhibit NF-kappaB signaling and reduce the expression of bcl-2. In this study, we compared the intracellular localization of AS1411-modified TDNs (Apt-TDNs) with that of TDNs in different cells under hypoxic condition. Furthermore, we compared the effects of Apt-TDNs and TDNs on cell growth and cell cycle under hypoxic condition. A substantial amount of Apt TDNs entered and accumulated in the nucleus of MCF-7 cells; however, the amount of Apt-TDNs that entered L929 cells was comparatively less. TDNs entered in much lower quantity in MCF-7 cells than Apt-TDNs. Moreover, there was little difference in the amount of TDNs that entered L929 cells and MCF-7 cells. Apt TDNs can inhibit MCF-7 cell growth and promote L929 cell growth, while TDNs can promote both MCF-7 and L929 cell growth. Thus, the results indicate that Apt-TDNs are more effective tumor-targeted drug delivery vehicles than TDNs, with the ability to specifically inhibit tumor cell growth. PMID- 28991437 TI - Structural Insight into Acyl-ACP Thioesterase toward Substrate Specificity Design. AB - Acyl-ACP thioesterase (TE) catalyzes the hydrolysis of thioester bonds during type II fatty acid synthesis and directly determines fatty acid chain length. Most TEs are responsible for recognition of 16:0 and 18:1 substrates, while specific TEs interrupt acyl-ACP elongation at C8-C14. However, the acyl selection mechanism of TE has not been thoroughly elucidated to date. In this study, the crystal structure of the C12-specific thioesterase FatB from Umbellularia californica, which consists of two independent hotdog domains, was determined. An uncanonical Asp-His-Glu catalytic network was identified on the C-terminal hotdog domain, whereas the substrate binding pocket was determined to be on the N terminal hotdog domain. Moreover, we elucidated UcFatB's substrate selection mechanism, which is accommodated by several unconservative amino acids on the beta5, beta2, and beta4 sheets and enclosed by T137 on the alpha1 helix. On this basis, the C12-specific TE was rationally redesigned toward C14 selectivity by tuning the substrate binding pocket capacity. The T137G mutant demonstrated comparative relative activity on C14 substrates compared to C12 substrates in vitro. Furthermore, the reconstructed UcFatB_T137G achieved C14 fatty acid content up to 40% in contrast to 10% C14 from the wild type in engineered E. coli cells. The unraveled substrate selection mechanism of TE provides a new strategy for tailoring fatty acid synthesis. PMID- 28991438 TI - Inkjet-Printed Electrodes on A4 Paper Substrates for Low-Cost, Disposable, and Flexible Asymmetric Supercapacitors. AB - Printed electronics is widely gaining much attention for compact and high performance energy-storage devices because of the advancement of flexible electronics. The development of a low-cost current collector, selection, and utilization of the proper material deposition tool and improvement of the device energy density are major challenges for the existing flexible supercapacitors. In this paper, we have reported an inkjet-printed solid-state asymmetric supercapacitor on commercial A4 paper using a low-cost desktop printer (EPSON L130). The physical properties of all inks have been carefully optimized so that the developed inks are within the printable range, i.e., Fromm number of 4 < Z < 14 for all inks. The paper substrate is made conducting (sheet resistance ~ 1.6 Omega/sq) by printing 40 layers of conducting graphene oxide (GO) ink on its surface. The developed conducting patterns on paper are further printed with a GO MnO2 nanocomposite ink to make a positive electrode, and another such structure is printed with activated carbon ink to form a negative electrode. A combination of both of these electrodes is outlaid by fabricating an asymmetric supercapacitor. The assembled asymmetric supercapacitor with poly(vinyl alcohol) (PVA)-LiCl gel electrolyte shows a stable potential window of 0-2.0 V and exhibits outstanding flexibility, good cyclic stability, high rate capability, and high energy density. The fabricated paper-substrate-based flexible asymmetric supercapacitor also displays an excellent electrochemical performances, e.g., a maximum areal capacitance of 1.586 F/cm2 (1023 F/g) at a current density of 4 mA/cm2, highest energy density of 22 mWh/cm3 at a power density of 0.099 W/cm3, a capacity retention of 89.6% even after 9000 charge-discharge cycles, and a low charge-transfer resistance of 2.3 Omega. So, utilization of inkjet printing for the development of paper-based flexible electronics has a strong potential for embedding into the next generation low-cost, compact, and wearable energy-storage devices and other printed electronic applications. PMID- 28991439 TI - Mild Periodic Acid Flux and Hydrothermal Methods for the Synthesis of Crystalline f-Element-Bearing Iodate Compounds. AB - f-element-bearing iodate compounds are a large family mostly synthesized by hydrothermal reactions starting with actinide/lanthanide ions and iodic acid or iodate salt. In this work, we introduce melting periodic acid flux as a new reaction medium and provide a safe way for single-crystal growth of a series of new f-element iodate compounds including UO2(IO3)2.H2O (1), UO2(IO3)2(H2O).HIO3 (2), alpha-Th(IO3)2(NO3)(OH) (3), beta-Th(IO3)2(NO3)(OH) (4), and (H3O)9Nd9(IO3)36.3HIO3 (5). The structures of these compounds deviate from those afforded from hydrothermal reactions. Specifically, compounds 1 and 2 exhibit pillared structures consisting of uranyl pentagonal bipyramids and iodate trigonal pyramids. Compounds 3 and 4 represent two new thorium iodate compounds that are constructed from subunits of thorium dimers. Compound 5 exhibits a flower-shaped trivalent lanthanide iodate structure with HIO3 molecules and H3O+ cations filled in the channels. The aliovalent replacement of f elements in 5 is available from a hydrothermal process, further generating compounds of Th2(IO3)8(H2O) (6) and Ce2(IO3)8(H2O) (7). The distinct absorption features are observed in isotypic compounds 5-7, where 7 shows typical semiconductor behavior with a band gap of 2.43 eV. Remarkably, noncentrosymmetric 1, 6, and 7 exhibit strong second-harmonic-generation efficiencies of 1.3, 3.2, and 9.2 times, respectively, that of the commercial material KH2PO4. Additionally, the temperature-dependent emission spectra of 1 and 2 were also collected showing typical emission features of uranyl units and a negative correlation between the intensities of the emissions with temperature. Clearly, the presented low temperature melting inorganic acid flux synthesis would provide a facile and effective strategy to produce a large new family of structurally versatile and multifunctional f-element inorganic compounds. PMID- 28991440 TI - Correction to Hydrophilic Phage-Mimicking Membrane Active Antimicrobials Reveal Nanostructure-Dependent Activity and Selectivity. PMID- 28991441 TI - Electrochemical, Spectroscopic, and 1O2 Sensitization Characteristics of Synthetically Accessible Linear Tetrapyrrole Complexes of Palladium and Platinum. AB - The synthesis, electrochemistry, and photophysical characterization of a 10,10 dimethyl-5,15-bis(pentafluorophenyl)biladiene (DMBil1) linear tetrapyrrole supporting PdII or PtII centers is presented. Both of these nonmacrocyclic tetrapyrrole platforms are robust and easily prepared via modular routes. X-ray diffraction experiments reveal that the Pd[DMBil1] and Pt[DMBil1] complexes adopt similar structures and incorporate a single PdII and PtII center, respectively. Additionally, electrochemical experiments revealed that both Pd[DMBil1] and Pt[DMBil1] can undergo two discrete oxidation and reduction processes. Spectroscopic experiments carried out for Pd[DMBil1] and Pt[DMBil1] provide further understanding of the electronic structure of these systems. Both complexes strongly absorb light in the UV-visible region, especially in the 350 600 nm range. Both Pd[DMBil1] and Pt[DMBil1] are luminescent under a nitrogen atmosphere. Upon photoexcitation of Pd[DMBil1], two emission bands are observed; fluorescence is detected from ~500-700 nm and phosphorescence from ~700-875 nm. Photoexcitation of Pt[DMBil1] leads only to phosphorescence, presumably due to enhanced intersystem crossing imparted by the heavier PtII center. Phosphorescence from both complexes is quenched under air due to energy transfer from the excited triplet state to ground state oxygen. Accordingly, irradiation with light of lambda >= 500 nm prompts Pd[DMBil1] and Pt[DMBil1] to photosensitize the generation of 1O2 (singlet oxygen) with impressive quantum yields of 80% and 78%, respectively. The synthetic accessibility of these complexes coupled with their ability to efficiently photosensitize 1O2 may make them attractive platforms for development of new agents for photodynamic therapy. PMID- 28991442 TI - Ultrafine Particle Production from the Ozonolysis of Personal Care Products. AB - Personal care products (PCP) might be a source of ultrafine particle exposure for users owing to the reaction of ozone with terpene ingredients. The near-person emissions associated with PCP may contribute to exposures that would not be properly accounted for with indoor microenvironmental measurements. To better understand this issue, screening experiments were conducted with 91 PCP to detect the occurrence of ultrafine particle production from exposure to common indoor levels of ozone (23 +/- 2 ppb). Twelve products generated measurable particle emissions; quantification experiments were performed for these to determine total particle production and peak particle production rate. A high-resolution, small volume reaction chamber was used with a heated sample plate to simulate conditions found in the human thermal plume. Ten of the quantified PCP exhibited total emissions of less than 109 particles, suggesting that they may not be significant sources of total ultrafine particle exposure. Two samples, a tea tree oil-based scalp treatment and a white lavender body lotion, exhibited relatively elevated peak particle emission rates, 6.2 * 107 min-1 and 2.0 * 107 min-1, respectively. The use of such products in the presence of significant ozone levels might materially influence personal exposure to ultrafine particles. PMID- 28991443 TI - Renewable Alkenes from the Hydrothermal Treatment of Polyhydroxyalkanoates Containing Sludge. AB - Polyhydroxyalkanoates (PHA) are a key constituent of excess sludge produced by Aerobic Sewage Sludge Treatment plants. The accumulation of significant amount of PHA inside aerobic microbial cells occurs when a surplus of an easily degradable carbon source (e.g., volatile fatty acids, VFA) is found in combination with other nutrients limitation. Herein, hydrothermal treatment (HT) of PHA-containing sludge at 300 and 375 degrees C was demonstrated to be effective in converting most (>70% w/w) of the bacterial PHA stored inside microbial cells into alkene/CO2 gas mixtures. Simultaneously, most of non-PHA biomass was converted into water-soluble compounds (50% carbon yield) that were acidogenic fermented to produce volatile fatty acids, ideal substrate to feed aerobic bacteria and produce more PHA. According to results here presented, HT of excess sludge with moderate (13%) PHA content can produce about 50 kg of alkenes per tonne of suspended solids treated, with a significant reduction of sludge mass (80% reduction of wet sludge volume) and consequent disposal cost. PMID- 28991444 TI - Enhanced ~2 MUm Emission of Tm3+ in Lu2O3 by Addition of a Trace Amount of Er3. AB - Er3+-induced intensity enhancement of ~2 MUm emission is observed in 2 atom % Tm3+ doped Lu2O3 under 782 nm excitation. The maximum enhancement reaches 41.9% with only 0.05 atom % Er3+. Er3+ introduces a new quantum cutting process which is proved to be a Tm3+ -> Er3+ -> Tm3+ forward-backward energy transfer (FBET) system. The FBET system is observed to work efficiently even at very low Er3+ concentration. Thus, energy loss due to energy migration among Tm3+ ions is suggested to be suppressed by the FBET process. The Tm3+ -> Er3+ -> Tm3+ FBET system may be a new route to improve the performance of Tm3+ lasers. PMID- 28991445 TI - A Permanently Porous Yttrium-Organic Framework Based on an Extended Tridentate Phosphine Containing Linker. AB - The metal-organic framework [Y(tbpp)].nDMF (1) was synthesized from yttrium(III) nitrate and the tritopic linker tris(4'-carboxy[1,1'-biphenyl]-4-yl)phosphine (H3tbpp). The distance between the coordinating atoms of the carboxylate groups of the extended tridentate phosphine linker is more than 1.8 nm, resulting in an average pore dimension of 0.9 nm in the noninterpenetrated metal-organic framework. The material exhibits high thermal stability and permanent porosity after removal of guest molecules from the one-dimensional pore system. The desolvated compound adsorbs nitrogen, argon, hydrogen, and carbon dioxide. Favorable adsorption of CO2 over N2 is predicted using ideal adsorbed solution theory (IAST). The isosteric enthalpies of adsorption of H2 and CO2 of -7 and -22 kJ mol-1, respectively, are representative for metal-organic frameworks with no accessible strong host-guest binding sites, despite the bifunctional nature of the organic ligand. The absence of strong specific adsorption sites was confirmed by in situ powder synchrotron X-ray diffraction of the reversible isobaric CO2 sorption process. Analysis of the diffraction data indicates that the CO2 molecules in the pores are disordered and nonlocalized. Despite this, it was possible to quantify the evolution of the occupation of the pores. CO2 is adsorbed at an approximately constant below 320 K from 10% loading to full capacity at 195 K. PMID- 28991446 TI - Photochemistry and Anion-Controlled Structure of Fe(III) Complexes with an alpha Hydroxy Acid-Containing Tripodal Amine Chelate. AB - The tripodal amine chelate with two pyridyl groups and an alpha-hydroxy acid (AHA) group, Pyr-TPA-AHA, was synthesized. Different Fe(III) complexes form with this chelate depending upon the counterion of the Fe(III) source used in the synthesis. A dinuclear complex, Fe(III)2(Pyr-TPA-AHA)2(MU-O), 1, and mononuclear complexes Fe(III)(Pyr-TPA-AHA)X (X = Cl- or Br-, 2 and 3, respectively) were synthesized. 2 can be easily converted to 1 by addition of silver nitrate or a large excess of water. The structure of 1 was solved by X-ray crystallography (C32H34N6O7Fe2.13H2O, a = 14.1236(6) A, b = 14.1236(6) A, c = 21.7469(15) A, alpha = beta = gamma = 90 degrees , tetragonal, P42212, Z = 4). 2 and 3 each have simple quasireversible cyclic voltammograms with E1/2 (vs aqueous Ag/AgCl) = +135 mV for 2 and +470 for 3 in acetonitrile. The cyclic voltammogram for 1 in acetonitrile has a quasireversible feature at E1/2 = -285 mV and an irreversible cathodic feature at -1140 mV. All three complexes are photochemically active upon irradiation with UV light, resulting in cleavage of the AHA group and reduction of the iron to Fe(II). Photolysis of 1 results in reduction of both Fe(III) ions in the dinuclear complex for each AHA group that is cleaved, while photolysis of 2 and 3 results in reduction of a single Fe(III) for each AHA cleavage. The quantum yields for 2 and 3 are significantly higher than that of 1. PMID- 28991447 TI - Rigid Oxazole Acinetobactin Analog Blocks Siderophore Cycling in Acinetobacter baumannii. AB - The emergence of multidrug resistant (MDR) Gram-negative bacterial pathogens has raised global concern. Nontraditional therapeutic strategies, including antivirulence approaches, are gaining traction as a means of applying less selective pressure for resistance in vivo. Here, we show that rigidifying the structure of the siderophore preacinetobactin from MDR Acinetobacter baumannii via oxidation of the phenolate-oxazoline moiety to a phenolate-oxazole results in a potent inhibitor of siderophore transport and imparts a bacteriostatic effect at low micromolar concentrations under infection-like conditions. PMID- 28991448 TI - Structure Evolution and Spin-Glass Transition of Layered Compounds ALiFeSe2 (A = Na, K, Rb). AB - Three new layered compounds, namely NaLiFeSe2, KLiFeSe2, and RbLiFeSe2, have been discovered. NaLiFeSe2 adopts a trigonal CaAl2Si2-type structure with space group P3m1, while the other two possess a tetragonal ThCr2Si2-type structure with space group I4/mmm. Structural refinements reveal that Li and Fe atoms randomly occupy the same sites in all these compounds without ordering. It is found that the radius of the alkali metals plays a vital role in determining the symmetry of this series of compounds. The substitution of Li at the Fe site shortens the layer spacing and elongates the A-Se bond length in the ThCr2Si2-type structure. The elongated Na-Se bond length would destabilize the ThCr2Si2-type structure in NaLiFeSe2, suggesting that NaxFe2-ySe2 lies at the border of ThCr2Si2-type and CaAl2Si2-type structures. Magnetic and resistivity measurements demonstrate that these compounds exhibit anisotropic spin-glass and narrow-band-gap semiconducting characteristics. First-principles calculations indicate that the introduction of Li enhances strong localization and weakens the correlation of the 3d electrons of Fe, which are responsible for the observed spin-glass transition and semiconducting conductions. PMID- 28991449 TI - Metal-Involving Synthesis and Reactions of Oximes. AB - This review classifies and summarizes the past 10-15 years of advancements in the field of metal-involving (i.e., metal-mediated and metal-catalyzed) reactions of oximes. These reactions are diverse in nature and have been employed for syntheses of oxime-based metal complexes and cage-compounds, oxime functionalizations, and the preparation of new classes of organic species, in particular, a wide variety of heterocyclic systems spanning small 3-membered ring systems to macroheterocycles. This consideration gives a general outlook of reaction routes, mechanisms, and driving forces and underlines the potential of metal-involving conversions of oxime species for application in various fields of chemistry and draws attention to the emerging putative targets. PMID- 28991450 TI - Nature-Inspired Structural Materials for Flexible Electronic Devices. AB - Exciting advancements have been made in the field of flexible electronic devices in the last two decades and will certainly lead to a revolution in peoples' lives in the future. However, because of the poor sustainability of the active materials in complex stress environments, new requirements have been adopted for the construction of flexible devices. Thus, hierarchical architectures in natural materials, which have developed various environment-adapted structures and materials through natural selection, can serve as guides to solve the limitations of materials and engineering techniques. This review covers the smart designs of structural materials inspired by natural materials and their utility in the construction of flexible devices. First, we summarize structural materials that accommodate mechanical deformations, which is the fundamental requirement for flexible devices to work properly in complex environments. Second, we discuss the functionalities of flexible devices induced by nature-inspired structural materials, including mechanical sensing, energy harvesting, physically interacting, and so on. Finally, we provide a perspective on newly developed structural materials and their potential applications in future flexible devices, as well as frontier strategies for biomimetic functions. These analyses and summaries are valuable for a systematic understanding of structural materials in electronic devices and will serve as inspirations for smart designs in flexible electronics. PMID- 28991452 TI - Single-Mode Lasers Based on Cesium Lead Halide Perovskite Submicron Spheres. AB - Single-mode laser is realized in a cesium lead halide perovskite submicron sphere at room temperature. All-inorganic cesium lead halide (CsPbX3, X = Cl, Br, I) microspheres with tunable sizes (0.2-10 MUm) are first fabricated by a dual source chemical vapor deposition method. Due to smooth surface and regular geometry structure of microspheres, whispering gallery resonant modes make a single-mode laser realized in a submicron sphere. Surprisingly, a single-mode laser with a very narrow line width (~0.09 nm) was achieved successfully in the CsPbX3 spherical cavity at low threshold (~0.42 MUJ cm-2) with a high cavity quality factor (~6100), which are the best specifications of lasing modes in all natural nano/microcavities ever reported. By modulating the halide composition and sizes of the microspheres, the wavelength of a single-mode laser can be continuously tuned from red to violet (425-715 nm). This work illustrates that the well-controlled synthesis of metal cesium lead halide perovskite nano/microspheres may offer an alternative route to produce a widely tunable and greatly miniaturized single-mode laser. PMID- 28991451 TI - Biomimetic Reactivity of Oxygen-Derived Manganese and Iron Porphyrinoid Complexes. AB - Heme proteins utilize the heme cofactor, an iron porphyrin, to perform a diverse range of reactions including dioxygen binding and transport, electron transfer, and oxidation/oxygenations. These reactions share several key metalloporphyrin intermediates, typically derived from dioxygen and its congeners such as hydrogen peroxide. These species are composed of metal-dioxygen, metal-superoxo, metal peroxo, and metal-oxo adducts. A wide variety of synthetic metalloporphyrinoid complexes have been synthesized to generate and stabilize these intermediates. These complexes have been studied to determine the spectroscopic features, structures, and reactivities of such species in controlled and well-defined environments. In this Review, we summarize recent findings on the reactivity of these species with common porphyrinoid scaffolds employed for biomimetic studies. The proposed mechanisms of action are emphasized. This Review is organized by structural type of metal-oxygen intermediate and broken into subsections based on the metal (manganese and iron) and porphyrinoid ligand (porphyrin, corrole, and corrolazine). PMID- 28991453 TI - Active Site Structures of CYP11A1 in the Presence of Its Physiological Substrates and Alterations upon Binding of Adrenodoxin. AB - The rate-limiting step in the steroid synthesis pathway is catalyzed by CYP11A1 through three sequential reactions. The first two steps involve hydroxylations at positions 22 and 20, generating 20(R),22(R)-dihydroxycholesterol (20R,22R DiOHCH), with the third stage leading to a C20-C22 bond cleavage, forming pregnenolone. This work provides detailed information about the active site structure of CYP11A1 in the resting state and substrate-bound ferric forms as well as the CO-ligated adducts. In addition, high-quality resonance Raman spectra are reported for the dioxygen complexes, providing new insight into the status of Fe-O-O fragments encountered during the enzymatic cycle. Results show that the three natural substrates of CYP11A1 have quite different effects on the active site structure, including variations of spin state populations, reorientations of heme peripheral groups, and, most importantly, substrate-mediated distortions of Fe-CO and Fe-O2 fragments, as revealed by telltale shifts of the observed vibrational modes. Specifically, the vibrational mode patterns observed for the Fe-O-O fragments with the first and third substrates are consistent with H bonding interactions with the terminal oxygen, a structural feature that tends to promote O-O bond cleavage to form the Compound I intermediate. Furthermore, such spectral data are acquired for complexes with the natural redox partner, adrenodoxin (Adx), revealing protein-protein-induced active site structural perturbations. While this work shows that Adx has an only weak effect on ferric and ferrous CO states, it has a relatively stronger impact on the Fe-O-O fragments of the functionally relevant oxy complexes. PMID- 28991456 TI - Functional and Biomimetic Materials for Engineering of the Three-Dimensional Cell Microenvironment. AB - The cell microenvironment has emerged as a key determinant of cell behavior and function in development, physiology, and pathophysiology. The extracellular matrix (ECM) within the cell microenvironment serves not only as a structural foundation for cells but also as a source of three-dimensional (3D) biochemical and biophysical cues that trigger and regulate cell behaviors. Increasing evidence suggests that the 3D character of the microenvironment is required for development of many critical cell responses observed in vivo, fueling a surge in the development of functional and biomimetic materials for engineering the 3D cell microenvironment. Progress in the design of such materials has improved control of cell behaviors in 3D and advanced the fields of tissue regeneration, in vitro tissue models, large-scale cell differentiation, immunotherapy, and gene therapy. However, the field is still in its infancy, and discoveries about the nature of cell-microenvironment interactions continue to overturn much early progress in the field. Key challenges continue to be dissecting the roles of chemistry, structure, mechanics, and electrophysiology in the cell microenvironment, and understanding and harnessing the roles of periodicity and drift in these factors. This review encapsulates where recent advances appear to leave the ever-shifting state of the art, and it highlights areas in which substantial potential and uncertainty remain. PMID- 28991457 TI - Trifluoroacetophenone-Linked Nucleotides and DNA for Studying of DNA-Protein Interactions by 19F NMR Spectroscopy. AB - A series of 7-[4-(trifluoroacetyl)phenyl]-7-deazaadenine and -7-deazaguanine as well as 5-substituted uracil and cytosine 2'-deoxyribonucleosides and mono- and triphosphates were synthesized through aqueous Suzuki-Miyaura crosscoupling of halogenated nucleosides or nucleotides with 4-(trifluoroacetyl)phenylboronic acid. The modified nucleoside triphosphates were good substrates for DNA polymerases applicable in primer extension or PCR synthesis of modified oligonucleotides or DNA. Attempted cross-linking with a serine-containing protein did not proceed, however the trifluoroacetophenone group was a sensitive probe for the study of DNA-protein interactions by 19F NMR. PMID- 28991458 TI - Homoleptic Trivalent Tris(alkyl) Rare Earth Compounds. AB - Homoleptic tris(alkyl) rare earth complexes Ln{C(SiHMe2)3}3 (Ln = La, 1a; Ce, 1b; Pr, 1c; Nd, 1d) are synthesized in high yield from LnI3THFn and 3 equiv of KC(SiHMe2)3. X-ray diffraction studies reveal 1a-d are isostructural, pseudo-C3 symmetric molecules that contain two secondary Ln?HSi interactions per alkyl ligand (six total). Spectroscopic assignments are supported by comparison with Ln{C(SiDMe2)3}3 and DFT calculations. The Ln?HSi and terminal SiH exchange rapidly on the NMR time scale at room temperature, but the two motifs are resolved at low temperature. Variable-temperature NMR studies provide activation parameters for the exchange process in 1a (DeltaH? = 8.2(4) kcal.mol-1; DeltaS? = -1(2) cal.mol-1K-1) and 1a-d9 (DeltaH? = 7.7(3) kcal.mol-1; DeltaS? = -4(2) cal.mol-1K-1). Comparisons of lineshapes, rate constants (kH/kD), and slopes of ln(k/T) vs 1/T plots for 1a and 1a-d9 reveal that an inverse isotope effect dominates at low temperature. DFT calculations identify four low-energy intermediates containing five beta-Si-H?Ln and one gamma-C-H?Ln. The calculations also suggest the pathway for Ln?HSi/SiH exchange involves rotation of a single C(SiHMe2)3 ligand that is coordinated to the Ln center through the Ln-C bond and one secondary interaction. These robust organometallic compounds persist in solution and in the solid state up to 80 degrees C, providing potential for their use in a range of synthetic applications. For example, reactions of Ln{C(SiHMe2)3}3 and ancillary proligands, such as bis-1,1-(4,4-dimethyl-2 oxazolinyl)ethane (HMeC(OxMe2)2) give {MeC(OxMe2)2}Ln{C(SiHMe2)3}2, and reactions with disilazanes provide solvent-free lanthanoid tris(disilazides). PMID- 28991455 TI - Pyrazinoic Acid Inhibits Mycobacterial Coenzyme A Biosynthesis by Binding to Aspartate Decarboxylase PanD. AB - Previously, we showed that a major in vitro and in vivo mechanism of resistance to pyrazinoic acid (POA), the bioactive component of the critical tuberculosis (TB) prodrug pyrazinamide (PZA), involves missense mutations in the aspartate decarboxylase PanD, an enzyme required for coenzyme A biosynthesis. What is the mechanism of action of POA? Upon demonstrating that treatment of M. bovis BCG with POA resulted in a depletion of intracellular coenzyme A and confirming that this POA-mediated depletion is prevented by either missense mutations in PanD or exogenous supplementation of pantothenate, we hypothesized that POA binds to PanD and that this binding blocks the biosynthetic pathway. Here, we confirm both hypotheses. First, metabolomic analyses showed that POA treatment resulted in a reduction of the concentrations of all coenzyme A precursors downstream of the PanD-mediated catalytic step. Second, using isothermal titration calorimetry, we established that POA, but not its prodrug PZA, binds to PanD. Binding was abolished for mutant PanD proteins. Taken together, these findings support a mechanism of action of POA in which the bioactive component of PZA inhibits coenzyme A biosynthesis via binding to aspartate decarboxylase PanD. Together with previous works, these results establish PanD as a genetically, metabolically, and biophysically validated target of PZA. PMID- 28991459 TI - Methyl 3-(3-(4-(2,4,4-Trimethylpentan-2-yl)phenoxy)-propanamido)benzoate as a Novel and Dual Malate Dehydrogenase (MDH) 1/2 Inhibitor Targeting Cancer Metabolism. AB - Previously, we reported a hypoxia-inducible factor (HIF)-1 inhibitor LW6 containing an (aryloxyacetylamino)benzoic acid moiety inhibits malate dehydrogenase 2 (MDH2) using a chemical biology approach. Structure-activity relationship studies on a series of (aryloxyacetylamino)benzoic acids identified selective MDH1, MDH2, and dual inhibitors, which were used to study the relationship between MDH enzyme activity and HIF-1 inhibition. We hypothesized that dual inhibition of MDH1 and MDH2 might be a powerful approach to target cancer metabolism and selected methyl-3-(3-(4-(2,4,4-trimethylpentan-2 yl)phenoxy)propanamido)-benzoate (16c) as the most potent dual inhibitor. Kinetic studies revealed that compound 16c competitively inhibited MDH1 and MDH2. Compound 16c inhibited mitochondrial respiration and hypoxia-induced HIF-1alpha accumulation. In xenograft assays using HCT116 cells, compound 16c demonstrated significant in vivo antitumor efficacy. This finding provides concrete evidence that inhibition of both MDH1 and MDH2 may provide a valuable platform for developing novel therapeutics that target cancer metabolism and tumor growth. PMID- 28991460 TI - A Smart Europium-Ruthenium Complex as Anticancer Prodrug: Controllable Drug Release and Real-Time Monitoring under Different Light Excitations. AB - A unique, dual-function, photoactivatable anticancer prodrug, RuEuL, has been tailored that features a ruthenium(II) complex linked to a cyclen-europium chelate via a pi-conjugated bridge. Under irradiation at 488 nm, the dark inactive prodrug undergoes photodissociation, releasing the DNA-damaging ruthenium species. Under evaluation-window irradiation (lambdairr = one-photon 350 nm or two-photon 700 nm), the drug delivery process can be quantitatively monitored in real-time because of the long-lived red europium emission. Linear relationships between released drug concentration and ESI-MS or luminescence responses are established. Finally, the efficiency of the new prodrug is demonstrated both in vitro RuEuL anticancer prodrug over some existing ones and open the way for decisive improvements in multipurpose prodrugs. PMID- 28991461 TI - Passive Adsorption of Volatile Monoterpene in Pest Control: Aided by Proximity and Disrupted by Ozone. AB - Plant volatiles mediate a range of interactions across and within trophic levels, including plant-plant interactions. Volatiles emitted by a plant may trigger physiological responses in neighboring plants or adhere to their surfaces, which, in turn, may affect the responses of the neighboring plant to herbivory. These volatiles are subject to chemical reactions during transport in air currents, especially in a polluted atmosphere. We conducted a field experiment to test for the adsorption of dispenser-released myrcene on the surfaces of cabbage plants and the effects of distance from the dispenser and elevated ozone levels (1.4* ambient) on the process. We also tested the effects of the same treatments on oviposition on cabbage plants by naturally occurring Plutella xylostella. Under low ambient ozone conditions of central Finland, there was evidence for the adsorption and re-release of myrcene by cabbage plants growing at a distance of 50 cm from myrcene dispensers. This effect was absent at elevated ozone levels. The number of eggs deposited by P. xylostella was generally lower in plots under elevated ozone compared to ambient control plots. Our results indicate that passive adsorption and re-release of a volatile monoterpene can occur in nature; however, this process is dependent upon the distance between emitter source and receiver plants as well as the concentration of atmospheric pollutants in the air. We conclude that, in the development of field-scale use of plant volatiles in modern pest control, the effects of distances and air pollution should be considered. PMID- 28991463 TI - Phase Change Transformations with Dynamically Addressable Aminal Metallogels. AB - Dynamic polymers assembled through hemiaminal and aminal functionalities reversibly fragment upon binding to trivalent metals. Gels produced with these dynamic polymers are broken down to liquids after the addition of metal salts. Nuclear magnetic resonance spectroscopy studies and density functional theory calculations of intermediates reveal that the presence of these metals causes shifts in the energetic landscape of the intermediates in the condensation pathway to render stable nonequilibrium products. These species remain stable in the liquid phase at room temperature but convert to gels upon heating. With thermal activation, the fragmented ligands transform catalytically into closed ring hexahydrotriazine products, which are macroscopically observable as new gels with distinct physical properties. The interplay between equilibrium and nonequilibrium gels and liquids and the ligands responsible for these transformations has been observed rheologically, giving controlled gel times dictated by the thermodynamics and kinetics of the system. This constitutionally dynamic macromolecular system offers the possibility of harnessing an equilibrium/nonequilibrium system in tandem with its inherent self-healing properties and triggered release functionality. PMID- 28991462 TI - Structure-Activity Relationship, Pharmacological Characterization, and Molecular Modeling of Noncompetitive Inhibitors of the Betaine/gamma-Aminobutyric Acid Transporter 1 (BGT1). AB - N-(1-Benzyl-4-piperidinyl)-2,4-dichlorobenzamide 5 (BPDBA) is a noncompetitive inhibitor of the betaine/GABA transporter 1 (BGT1). We here report the synthesis and structure-activity relationship of 71 analogues. We identify 26m as a more soluble 2,4-Cl substituted 3-pyridine analogue with retained BGT1 activity and an improved off-target profile compared to 5. We performed radioligand-based uptake studies at chimeric constructs between BGT1 and GAT3, experiments with site directed mutated transporters, and computational docking in a BGT1 homology model based on the newly determined X-ray crystal structure of the human serotonin transporter (hSERT). On the basis of these experiments, we propose a binding mode involving residues within TM10 in an allosteric site in BGT1 that corresponds to the allosteric binding pocket revealed by the hSERT crystal structure. Our study provides first insights into a proposed allosteric binding pocket in BGT1, which accommodates the binding site for a series of novel noncompetitive inhibitors. PMID- 28991464 TI - Crystal Structure of Faradaurate-279: Au279(SPh-tBu)84 Plasmonic Nanocrystal Molecules. AB - We report the discovery of an unprecedentedly large, 2.2 nm diameter, thiolate protected gold nanocrystal characterized by single crystal X-ray crystallography (sc-XRD), Au279(SPh-tBu)84 named Faradaurate-279 (F-279) in honor of Michael Faraday's (1857) pioneering work on nanoparticles. F-279 nanocrystal has a core shell structure containing a truncated octahedral core with bulk face-centered cubic-like arrangement, yet a nanomolecule with a precise number of metal atoms and thiolate ligands. The Au279S84 geometry was established from a low temperature 120 K sc-XRD study at 0.90 A resolution. The atom counts in core shell structure of Au279 follows the mathematical formula for magic number shells: Au@Au12@Au42@Au92@Au54, which is further protected by a final shell of Au48. Au249 core is protected by three types of staple motifs, namely: 30 bridging, 18 monomeric, and 6 dimeric staple motifs. Despite the presence of such diverse staple motifs, Au279S84 structure has a chiral pseudo-D3 symmetry. The core-shell structure can be viewed as nested, concentric polyhedra, containing a total of five forms of Archimedean solids. A comparison between the Au279 and Au309 cuboctahedral superatom model in shell-wise growth is illustrated. F-279 can be synthesized and isolated in high purity in milligram quantities using size exclusion chromatography, as evidenced by mass spectrometry. Electrospray ionization-mass spectrometry independently verifies the X-ray diffraction study based heavy atoms formula, Au279S84, and establishes the molecular formula with the complete ligands, namely, Au279(SPh-tBu)84. It is also the smallest gold nanocrystal to exhibit metallic behavior, with a surface plasmon resonance band around 510 nm. PMID- 28991454 TI - Synthetic Organic Electrochemical Methods Since 2000: On the Verge of a Renaissance. AB - Electrochemistry represents one of the most intimate ways of interacting with molecules. This review discusses advances in synthetic organic electrochemistry since 2000. Enabling methods and synthetic applications are analyzed alongside innate advantages as well as future challenges of electroorganic chemistry. PMID- 28991465 TI - Inhibitors to Overcome Secondary Mutations in the Stem Cell Factor Receptor KIT. AB - In modern cancer therapy, the use of small organic molecules against receptor tyrosine kinases (RTKs) has been shown to be a valuable strategy. The association of cancer cells with dysregulated signaling pathways linked to RTKs represents a key element in targeted cancer therapies. The tyrosine kinase mast/stem cell growth factor receptor KIT is an example of a clinically relevant RTK. KIT is targeted for cancer therapy in gastrointestinal stromal tumors (GISTs) and chronic myelogenous leukemia (CML). However, acquired resistance mutations within the catalytic domain decrease the efficacy of this strategy and are the most common cause of failed therapy. Here, we present the structure-based design and synthesis of novel type II kinase inhibitors to overcome these mutations in KIT. Biochemical and cellular studies revealed promising molecules for the inhibition of mutated KIT. PMID- 28991467 TI - Role of Solvation in Drug Design as Revealed by the Statistical Mechanics Integral Equation Theory of Liquids. AB - Recent developments and applications in theoretical methods focusing on drug design and particularly on the solvent effect in molecular recognition based on the three-dimensional reference interaction site model (3D-RISM) theory are reviewed. Molecular recognition, a fundamental molecular process in living systems, is known to be the functional mechanism of most drugs. Solvents play an essential role in molecular recognition processes as well as in ligand-protein interactions. The 3D-RISM theory is derived from the fundamental statistical mechanics theory, which reproduces all solvation thermodynamics naturally and has some advantages over conventional solvation methods, such as molecular simulation and the continuum model. Here, we review the basics of the 3D-RISM theory and methods of molecular recognition in its applications toward drug design. PMID- 28991466 TI - Enantioselective Recognition of Ammonium Carbamates in a Chiral Metal-Organic Framework. AB - Chiral metal-organic frameworks have attracted interest for enantioselective separations and catalysis because of their high crystallinity and pores with tunable shapes, sizes, and chemical environments. Chiral frameworks of the type M2(dobpdc) (M = Mg, Mn, Fe, Co, Ni, Zn; dobpdc4- = 4,4'-dioxidobiphenyl-3,3' dicarboxylate) seem particularly promising for potential applications because of their excellent stability, high internal surface areas, and strongly polarizing open metal coordination sites within the channels, but to date these materials have been isolated only in racemic form. Here, we demonstrate that when appended with the chiral diamine trans-1,2-diaminocyclohexane (dach), Mg2(dobpdc) adsorbs carbon dioxide cooperatively to form ammonium carbamate chains, and the thermodynamics of CO2 capture are strongly influenced by enantioselective interactions within the chiral pores of the framework. We further show that it is possible to access both enantiomers of Mg2(dobpdc) with high enantiopurity (>=90%) via framework synthesis in the presence of varying quantities of d panthenol, an inexpensive chiral induction agent. Investigation of dach M2(dobpdc) samples following CO2 adsorption-using single-crystal and powder X-ray diffraction, solid-state nuclear magnetic resonance spectroscopy, and density functional theory calculations-revealed that the ammonium carbamate chains interact extensively with each other and with the chiral M2(dobpdc) pore walls. Subtle differences in the non-covalent interactions accessible in each diastereomeric phase dramatically impact the thermodynamics of CO2 adsorption. PMID- 28991468 TI - Total Syntheses of (+)- and (-)-Tetrapetalones A and C. AB - Described herein are syntheses of the naturally occurring polyketides (-) tetrapetalones A and C and their respective enantiomers. The employed strategy involves initial assembly of a masked N-aryl tetramic acid which is advanced via a highly selective conjugate addition/intramolecular Friedel-Crafts acylation sequence to deliver a key azepine intermediate. Application of recently developed C-H activation chemistry and subsequent Heck cyclization delivers the aglycone framework in an overall 12 steps. Resolution of the aglycone via stereospecific glycosylation with an enantiopure glycosyl donor followed by separation of the derived diastereomers enables further advancement to either (+)- or (-) tetrapetalones A and C. PMID- 28991469 TI - Non-Metal-Catalyzed Heterodehydrocoupling of Phosphines and Hydrosilanes: Mechanistic Studies of B(C6F5)3-Mediated Formation of P-Si Bonds. AB - Non-metal-catalyzed heterodehydrocoupling of primary and secondary phosphines (R1R2PH, R2 = H or R1) with hydrosilanes (R3R4R5SiH, R4, R5 = H or R3) to produce synthetically useful silylphosphines (R1R2P-SiR3R4R5) has been achieved using B(C6F5)3 as the catalyst (10 mol %, 100 degrees C). Kinetic studies demonstrated that the reaction is first-order in hydrosilane and B(C6F5)3 but zero-order in phosphine. Control experiments, DFT calculations, and DOSY NMR studies suggest that a R1R2HP.B(C6F5)3 adduct is initially formed and undergoes partial dissociation to form an "encounter complex". The latter mediates frustrated Lewis pair type Si-H bond activation of the silane substrates. We also found that B(C6F5)3 catalyzes the homodehydrocoupling of primary phosphines to form cyclic phosphine rings and the first example of a non-metal-catalyzed hydrosilylation of P-P bonds to produce silylphosphines (R1R2P-SiR3R4R5). Moreover, the introduction of PhCN to the reactions involving secondary phosphines with hydrosilanes allowed the heterodehydrocoupling reaction to proceed efficiently under much milder conditions (1.0 mol % B(C6F5)3 at 25 degrees C). Mechanistic studies, as well as DFT calculations, revealed that PhCN plays a key mechanistic role in facilitating the dehydrocoupling reactions rather than simply functioning as H2-acceptor. PMID- 28991471 TI - Editorial: Excellence in Medicinal Chemistry from Australia. PMID- 28991470 TI - Synthesis of Scyphostatin Analogues through Hypervalent Iodine-Mediated Phenol Dearomatization. AB - A concise synthesis of two scyphostatin analogues is achieved from readily available ortho-substituted phenols. Key features include an asymmetric and biomimetic hydroxylative phenol dearomatization (HPD) reaction promoted by a chiral salen-type bis(lambda5-iodane) reagent, followed by an in situ regio- and diastereocontrolled epoxidation. PMID- 28991473 TI - INTerface Builder: A Fast Protein-Protein Interface Reconstruction Tool. AB - INTerface Builder (INTBuilder) is a fast, easy-to-use program to compute protein protein interfaces. It is designed to retrieve interfaces from molecular docking software outputs in an empirically determined linear complexity. INTBuilder directly reads the output formats of popular docking programs like ATTRACT, HEX, MAXDo, and ZDOCK, as well as a more generic format and Protein Data Bank (PDB) files. It identifies interacting surfaces at both residue and atom resolutions. INTerface Builder is an open source software written in C and freely available for noncommercial use (CeCILL license) at https://www.lcqb.upmc.fr/INTBuilder . PMID- 28991472 TI - The Discovery of a Dual TTK Protein Kinase/CDC2-Like Kinase (CLK2) Inhibitor for the Treatment of Triple Negative Breast Cancer Initiated from a Phenotypic Screen. AB - Triple negative breast cancer (TNBC) remains a serious unmet medical need with discouragingly high relapse rates. We report here the synthesis and structure activity relationship (SAR) of a novel series of 2,4,5-trisubstituted-7H pyrrolo[2,3-d]pyrimidines with potent activity against TNBC tumor cell lines. These compounds were discovered from a TNBC phenotypic screen and possess a unique dual inhibition profile targeting TTK (mitotic exit) and CLK2 (mRNA splicing). Design and optimization, driven with a TNBC tumor cell assay, identified potent and selective compounds with favorable in vitro and in vivo activity profiles and good iv PK properties. This cell-based driven SAR produced compounds with strong single agent in vivo efficacy in multiple TNBC xenograft models without significant body weight loss. These data supported the nomination of CC-671 into IND-enabling studies as a single agent TNBC therapy. PMID- 28991474 TI - Why Do Cumulene Ketones Kink? AB - We employ ab initio and density functional methods to investigate the equilibrium structure and vibrational frequencies of extended cumulene monoketones [CH2?(C?)mO] and diketones [O?(C?)mO], in order to elucidate the electronic origin of the curious "kinked'" spine geometries that are common in such species. The dominant role of symmetry-breaking nO(pi)-sigma*CC interactions between the p type lone pair of the terminal oxygen and adjacent unfilled CC antibonding orbital is demonstrated by NBO second-order delocalization energies, Fock matrix deletions, and natural resonance theory (NRT) descriptors, showing the general connection between cumulene kinking and CC bond-breaking reactions that split off CO. Our results provide simple rationalizations for (i) pronounced even/odd alternation patterns in the magnitude or direction of kinking, (ii) the nonexistence of O = C?C?O, (iii) the clear preference for trans-like over cis like kinks, and (iv) the extreme sensitivity of kinking with respect to weak perturbations, such as cage or solvent effects, remote chemical substituents, improved treatments of electron correlation, and the like. PMID- 28991475 TI - Cationic (Charge Shift) Exciplexes. AB - Of the many known examples of exciplexes, those formed from bimolecular encounter between a cationic, excited state electron acceptor and a neutral donor in fluid media have not been previously reported. We now show that emissive exciplexes formed from excited N-methyl isoquinolinium cation (NMiQ+) with alkyl benzene donors are readily detected in acetonitrile. These cationic exciplexes result in a charge shift (A+* + D -> A*D*+) with no net change in charge, which differs fundamentally from the charge-generation of conventional exciplex formation (A* + D -> A*-D*+). We find that cationic and conventional exciplexes show similar trends, e.g., bathochromic shifts and decreases in fluorescence quantum yields with decreasing oxidation potentials of the donors. In the presented examples of NMiQ+ exciplexes, the fluorescence quantum yield decreases by a factor of 30 and the radiative rate constant by 6.6 as the fractional CT character of the exciplex increases from ~0.79 to ~0.95. Interestingly, the electronic coupling matrix elements for the NMiQ+ exciplexes, derived from a correlation of the radiative rate constants with the average emission frequencies, are similar to those of related conventional exciplexes, in spite of the absence of Coulombic stabilization in the cationic exciplexes. PMID- 28991476 TI - Bridging Hydroxyls on Anatase TiO2(101) by Water Dissociation in Oxygen Vacancies. AB - Titanium dioxide is a promising candidate for photocatalytic H2 fuel production, and understanding water splitting on TiO2 surfaces is vital toward explaining and improving the generation of H2. In this work, we electron irradiate anatase TiO2(101) at room temperature to create metastable surface oxygen vacancies in order to investigate their ability to dissociate H2O. Our scanning tunneling microscopy investigations suggest that the surface oxygen vacancies can dissociate H2O by forming bridging OH species. This claim is supported by theoretical calculations from the literature and our previously published spectroscopic measurements. PMID- 28991477 TI - Unsymmetrical Relaxation Paths of the Excited States in Cyanine Dyes Detected by Time-Resolved Fluorescence: Polymethinic and Polyenic Forms. AB - Novel applications of organic dyes and vast opportunities for their molecular tailoring keep the focus of the scientific community on the issues of symmetry breaking in the systems having different location of uncompensated charge, which has tremendous impact on photoluminescent properties of the dyes. In this article, we provide distinctive experimental evidence of three relaxation paths (one symmetrical and two unsymmetrical) of excited states by analysis of lifetime and spectra of time-resolved fluorescence at low temperature with strong support of quantum-chemical modeling. Importantly, the studied cyanine dye (astraphloxin) in aqueous solution has two different unsymmetrical relaxation paths of excited states in the polymethinic and donor-acceptor polyenic forms, where the last form strongly diminishes in less polar media. The experimental and computational results provide essential fundamental knowledge of molecular electronic relaxations substantially affected by matrix rigidity and polarity for design and photonic applications of elongated pi-electronic systems. PMID- 28991478 TI - Role of Terahertz (THz) Fluctuations in the Allosteric Properties of the PDZ Domains. AB - With the aim of investigating the relationship between the fast fluctuations of proteins and their allosteric behavior, we perform molecular dynamics simulations of two model PDZ domains with differential allosteric responses. We focus on protein dynamics in the THz regime (0.1-3 THz) as opposed to lower frequencies. By characterizing the dynamic modulation of the protein backbone induced by ligand binding in terms of single residue and pairwise distance fluctuations, we identify a response nucleus modulated by the ligand that is visible only at THz frequencies. The residues of this nucleus undergo a significant stiffening and an increase in mutual coordination upon binding. Additionally, we find that the dynamic modulation is significantly more intense for the side chains, where it is also redistributed to distal regions not immediately in contact with the ligand allowing us to better define the response nucleus at THz frequencies. The overlap between the known allosterically responding residues of the investigated PDZ domains and the modulated region highlighted here suggests that fast THz dynamics could play a role in allosteric mechanisms. PMID- 28991479 TI - Breaking the Kasha Rule for More Efficient Photochemistry. AB - This paper provides a systematic review and analysis of different phenomena that violate a basic principle, Kasha's rule, when applied to photochemical reactions. In contrast to the classical route of ultrafast transition to the lowest energy excited state and photochemical reaction starting therein, in some cases, these reactions proceed directly from high-energy excited states. Nowadays, this phenomenon can be observed for a number of major types of excited-state reactions: harvesting product via intersystem crossing; photoisomerizations; bond breaking; and electron, proton, and energy transfers. We show that specific conditions for their observation are determined by kinetic factors. They should be among the fastest reactions in studied systems, competing with vibrational relaxation and radiative or nonradiative processes occurring in upper excited states. The anti-Kasha effects, which provide an important element that sheds light on the mechanisms of excited-state transformations, open new possibilities of selective control of these reactions for a variety of practical applications. Efficient utilization of excess electronic energy should enhance performance in the systems of artificial photosynthesis and photovoltaic devices. The modulation of the reporting signal by the energy of excitation of light should lead to new technologies in optical sensing and imaging. PMID- 28991480 TI - CH4 Hydrate Formation between Silica and Graphite Surfaces: Insights from Microsecond Molecular Dynamics Simulations. AB - Microsecond simulations have been performed to investigate CH4 hydrate formation from gas/water two-phase systems between silica and graphite surfaces, respectively. The hydrophilic silica and hydrophobic graphite surfaces exhibit substantially different effects on CH4 hydrate formation. The graphite surface adsorbs CH4 molecules to form a nanobubble with a flat or negative curvature, resulting in a low aqueous CH4 concentration, and hydrate nucleation does not occur during 2.5 MUs simulation. Moreover, an ordered interfacial water bilayer forms between the nanobubble and graphite surface thus preventing their direct contact. In contrast, the hydroxylated-silica surface prefers to be hydrated by water, with a cylindrical nanobubble formed in the solution, leading to a high aqueous CH4 concentration and hydrate nucleation in the bulk region; during hydrate growth, the nanobubble is gradually covered by hydrate solid and separated from the water phase, hence slowing growth. The silanol groups on the silica surface can form strong hydrogen bonds with water, and hydrate cages need to match the arrangements of silanols to form more hydrogen bonds. At the end of the simulation, the hydrate solid is separated from the silica surface by liquid water, with only several cages forming hydrogen bonds with the silica surface, mainly due to the low CH4 aqueous concentrations near the surface. To further explore hydrate formation between graphite surfaces, CH4/water homogeneous solution systems are also simulated. CH4 molecules in the solution are adsorbed onto graphite and hydrate nucleation occurs in the bulk region. During hydrate growth, the adsorbed CH4 molecules are gradually converted into hydrate solid. It is found that the hydrate-like ordering of interfacial water induced by graphite promotes the contact between hydrate solid and graphite. We reveal that the ability of silanol groups on silica to form strong hydrogen bonds to stabilize incipient hydrate solid, as well as the ability of graphite to adsorb CH4 molecules and induce hydrate-like ordering of the interfacial water, are the key factors to affect CH4 hydrate formation between silica and graphite surfaces. PMID- 28991481 TI - Development of a Superconducting Differential Double Contour Interferometer. AB - We study operation of a new device, the superconducting differential double contour interferometer (DDCI), in the application for the ultrasensitive detection of magnetic flux and for digital read out of the state of the superconducting flux qubit. DDCI consists of two superconducting contours weakly coupled by Josephson junctions. In such a device a change of the critical current, caused by an external magnetic flux or a nearby electric current, happens in a step-like manner when the angular momentum quantum number changes by one in one of the two contours. With a choice of parameters, the DDCI may outperform traditional superconducting quantum interference devices. PMID- 28991482 TI - Spontaneous Oscillations and Synchronization of Active Droplets on a Water Surface via Marangoni Convection. AB - Shape-oscillations and synchronization are intriguing phenomena in many biological and physical systems. Here, we report the rhythmic mechanical oscillations and synchronization of aniline oil droplets on a water phase, which is induced by Marangoni convection during transfer of the solute. The repetitive increase and decrease in the surface concentration in the vicinity of the contact line leads to the oscillations of droplets through an imbalance in surface tensions. The nature of the oscillations depends on the diameter of the droplet, the depth of the bulk aqueous phase, and the concentration of the aqueous phase. A numerical simulation reproduces the essential behaviors of active oscillations of a droplet. Droplets sense each other through a surface tension gradient and advection, and hydrodynamic coupling in the bulk solution induces the synchronization of droplet oscillations. PMID- 28991484 TI - Morphology Dynamics of Single-Layered Ni(OH)2/NiOOH Nanosheets and Subsequent Fe Incorporation Studied by in Situ Electrochemical Atomic Force Microscopy. AB - Nickel (oxy)hydroxide-based (NiOxHy) materials are widely used for energy storage and conversion devices. Understanding dynamic processes at the solid-liquid interface of nickel (oxy)hydroxide is important to improve reaction kinetics and efficiencies. In this study, in situ electrochemical atomic force microscopy (EC AFM) was used to directly investigate dynamic changes of single-layered Ni(OH)2 nanosheets during electrochemistry measurements. Reconstruction of Ni(OH)2 nanosheets, along with insertion of ions from the electrolyte, results in an increase of the volume by 56% and redox capacity by 300%. We also directly observe Fe cations adsorb and integrate heterogeneously into or onto the nanosheets as a function of applied potential, further increasing apparent volume. Our findings are important for the fundamental understanding of NiOxHy based supercapacitors and oxygen-evolution catalysts, illustrating the dynamic nature of Ni-based nanostructures under electrochemical conditions. PMID- 28991485 TI - One-Pot Synthesis of Indolizines via Sequential Rhodium-Catalyzed [2 + 1] Cyclopropanation, Palladium-Catalyzed Ring Expansion, and Oxidation Reactions from Pyridotriazoles and 1,3-Dienes. AB - An efficient, one-pot synthetic method for producing functionalized indolizine derivatives was developed via a Rh-catalyzed [2 + 1]-cyclopropanation, Pd catalyzed ring expansion, and subsequent oxidation using manganese dioxide from pyridotriazoles and 1,3-dienes. PMID- 28991483 TI - Vasoactive Intestinal Peptide Nanomedicine for the Management of Inflammatory Bowel Disease. AB - Inflammatory bowel disease (IBD) is a chronic relapsing disorder of the intestine, with increasing incidence worldwide. At present, the management of IBD is an unmet medical need due to the ineffectiveness of currently available drugs in treating all patients, and there is strong demand for novel therapeutics. In this regard, vasoactive intestinal peptide, a potent anti-inflammatory endogenous hormone, has shown promise in managing multiple immune disorders in animal models. However, when administered in the free form, VIP undergoes rapid degradation in vivo, and with continuous infusion, it causes severe dose limiting side effects. To overcome these barriers, we have developed a superior mode to deliver VIP in its native form, using sterically stabilized micelles (VIP-SSM). Our previous studies demonstrated that, VIP, when administered in SSM, prevented joint damage and inflammation in a mouse model of rheumatoid arthritis at a significantly lower dose than the free peptide, completely abrogating the serious side effect of hypotension associated with VIP. In the current study, we demonstrate the therapeutic benefit of VIP-SSM over free peptide in reversing severe colitis associated with IBD. First, we conducted preliminary studies with dextran sulfate sodium (DSS) induced colitis in mice, to determine the effectiveness of VIP administered on alternate days in reducing disease severity. Thereafter, a single intra peritoneal injection of VIP-SSM or the free peptide was used to determine its therapeutic effect on the reversal of colitis and associated diarrhea. The results demonstrated that when administered on alternate days, both VIP-SSM and VIP were capable of alleviating DSS colitis in mice. However, when administered as a single dose, in a therapeutic setting, VIP-SSM showed superior benefits compared to the free peptide in ameliorating colitis phenotype. Namely, the loss of solid fecal pellets and increased fluid accumulation in colon resulting from DSS insult was abrogated in VIP-SSM treated mice and not with free VIP. Furthermore, reduced protein and mRNA levels of the major chloride bicarbonate exchanger, down regulated in adenoma (DRA), seen with DSS was reversed with VIP-SSM, but not with the free peptide. Similarly, VIP-SSM treatment significantly reduced the elevated mRNA levels of pro-inflammatory cytokines and showed significant histologic recovery when compared to mice treated with free VIP. Therefore, these results demonstrated that as a single dose, the anti-inflammatory and antidiarrheal effects of VIP can be achieved effectively when administered as a nanomedicine. Therefore, we propose VIP-SSM to be developed as a potential therapeutic tool for treating ulcerative colitis, a type of IBD. PMID- 28991486 TI - Cobalt-Catalyzed Decarboxylative C-H (Hetero)Arylation for the Synthesis of Arylheteroarenes and Unsymmetrical Biheteroaryls. AB - A cobalt-catalyzed decarboxylative cross-coupling reaction of (hetero)aryl carboxylic acids with benzothiazoles or benzoxazoles is reported. This represents a first example of metal-catalyzed decarboxylative C-H heteroarylation of benzo fused heterocycles. The transformation provides a convenient route, with good yields and functional group tolerance, to various important arylheteroaryl and unsymmetrical biheteroaryl structural motifs. PMID- 28991487 TI - Structural Characterization of Rh and RhAu Dendrimer-Encapsulated Nanoparticles. AB - We report the structural characterization of 1-2 nm Rh and RhAu alloy dendrimer encapsulated nanoparticles (DENs) prepared by chemical reduction with NaBH4. In contrast to previously reported results, in situ and ex situ X-ray absorption spectroscopic experiments indicate that only a fraction of the Rh3+ present in the precursors are reduced by NaBH4. Additional structural analysis of RhAu alloy DENs using extended X-ray absorption fine structure spectroscopy leads to a model in which there is significant segregation of Rh and Au within the nanoparticles. In Rh-rich alloy DENs, Au atoms are segregated on the nanoparticle surface. PMID- 28991488 TI - Solar Transparent Radiators by Optical Nanoantennas. AB - Architectural windows are a major cause of thermal discomfort as the inner glazing during cold days can be several degrees colder than the indoor air. Mitigating this, the indoor temperature has to be increased, leading to unavoidable thermal losses. Here we present solar thermal surfaces based on complex nanoplasmonic antennas that can raise the temperature of window glazing by up to 8 K upon solar irradiation while transmitting light with a color rendering index of 98.76. The nanoantennas are directional, can be tuned to absorb in different spectral ranges, and possess a structural integrity that is not substrate-dependent, and thus they open up for application on a broad range of surfaces. PMID- 28991489 TI - Ripening of Semiconductor Nanoplatelets. AB - Ostwald ripening describes how the size distribution of colloidal particles evolves with time due to thermodynamic driving forces. Typically, small particles shrink and provide material to larger particles, which leads to size defocusing. Semiconductor nanoplatelets, thin quasi-two-dimensional (2D) particles with thicknesses of only a few atomic layers but larger lateral dimensions, offer a unique system to investigate this phenomenon. Experiments show that the distribution of nanoplatelet thicknesses does not defocus during ripening, but instead jumps sequentially from m to (m + 1) monolayers, allowing precise thickness control. We investigate how this counterintuitive process occurs in CdSe nanoplatelets. We develop a microscopic model that treats the kinetics and thermodynamics of attachment and detachment of monomers as a function of their concentration. We then simulate the growth process from nucleation through ripening. For a given thickness, we observe Ostwald ripening in the lateral direction, but none perpendicular. Thicker populations arise instead from nuclei that capture material from thinner nanoplatelets as they dissolve laterally. Optical experiments that attempt to track the thickness and lateral extent of nanoplatelets during ripening appear consistent with these conclusions. Understanding such effects can lead to better synthetic control, enabling further exploration of quasi-2D nanomaterials. PMID- 28991490 TI - Synthesis of Polyimides in Molecular-Scale Confinement for Low-Density Hybrid Nanocomposites. AB - In this work, we exploit a confinement-induced molecular synthesis and a resulting bridging mechanism to create confined polyimide thermoset nanocomposites that couple molecular confinement-enhanced toughening with an unprecedented combination of high-temperature properties at low density. We describe a synthesis strategy that involves the infiltration of individual polymer chains through a nanoscale porous network while simultaneous imidization reactions increase the molecular backbone stiffness. In the extreme limit where the confinement length scale is much smaller than the polymer's molecular size, confinement-induced molecular mechanisms give rise to exceptional mechanical properties. We find that polyimide oligomers can undergo cross-linking reactions even in such molecular-scale confinement, increasing the molecular weight of the organic phase and toughening the nanocomposite through a confinement-induced energy dissipation mechanism. This work demonstrates that the confinement-induced molecular bridging mechanism can be extended to thermoset polymers with multifunctional properties, such as excellent thermo-oxidative stability and high service temperatures (>350 degrees C). PMID- 28991491 TI - Nanowire Aptasensors for Electrochemical Detection of Cell-Secreted Cytokines. AB - Cytokines are small proteins secreted by immune cells in response to pathogens/infections; therefore, these proteins can be used in diagnosing infectious diseases. For example, release of a cytokine interferon (IFN)-gamma from T-cells is used for blood-based diagnosis of tuberculosis (TB). Our lab has previously developed an atpamer-based electrochemical biosensor for rapid and sensitive detection of IFN-gamma. In this study, we explored the use of silicon nanowires (NWs) as a way to create nanostructured electrodes with enhanced sensitivity for IFN-gamma. Si NWs were covered with gold and were further functionalized with thiolated aptamers specific for IFN-gamma. Aptamer molecules were designed to form a hairpin and in addition to terminal thiol groups contained redox reporter molecules methylene blue. Binding of analyte to aptamer modified NWs (termed here nanowire aptasensors) inhibited electron transfer from redox reporters to the electrode and caused electrochemical redox signal to decrease. In a series of experiments we demonstrate that NW aptasensors responded 3* faster and were 2* more sensitive to IFN-gamma compared to standard flat electrodes. Most significantly, NW aptasensors allowed detection of IFN-gamma from as few as 150 T-cells/mL while ELISA did not pick up signal from the same number of cells. One of the challenges faced by ELISA-based TB diagnostics is poor performance in patients whose T-cell numbers are low, typically HIV patients. Therefore, NW aptasensors developed here may be used in the future for more sensitive monitoring of IFN-gamma responses in patients coinfected with HIV/TB. PMID- 28991492 TI - Self-Templated Synthesis of Porous Ni(OH)2 Nanocube and Its High Electrochemical Performance for Supercapacitor. AB - Porous Ni(OH)2 nanocubes were successfully fabricated by a simple self sacrificial-template protocol using Ni-Co Prussian blue analogue (PBA) as precursor. When treated with NaOH, the simultaneous corrosion of Ni-Co PBA precursor and formation of amorphous Ni(OH)2 resulted in porous Ni(OH)2 nanocubes with uniform size of about 100 nm. Due to the large specific surface area and unique regular porous structure, the as-prepared materials showed large specific capacitance, relatively stable rate capability and long cycle stability when used as electrode materials for supercapacitors. With the voltage between 0.00 and 0.45 V versus Ag/AgCl, the specific capacitance can achieve 1842 F/g at a current density of 1 A/g. PMID- 28991493 TI - Silyl Ether as a Robust and Thermally Stable Dynamic Covalent Motif for Malleable Polymer Design. AB - Here we introduce silyl ether linkage as a novel dynamic covalent motif for dynamic material design. Through introduction of a neighboring amino moiety, we show that the silyl ether exchange rate can be accelerated by almost three orders of magnitude. By incorporating such silyl ether linkages into covalently cross linked polymer networks, we demonstrate dynamic covalent network polymers displaying both malleability and reprocessability. The malleability of the networks is studied by monitoring stress relaxation at varying temperature, and their topology freezing temperatures are determined. The tunable dynamic properties coupled with the high thermal stability and reprocessability of silyl ether-based networks open doors to many potential applications for this family of materials. PMID- 28991494 TI - Unidirectional Doubly Enhanced MoS2 Emission via Photonic Fano Resonances. AB - Atomically thin transition metal dichalcogenides like MoS2 monolayers exhibit unique luminescent properties. However, weak quantum yield and low light absorption hinder their practical applications in two-dimensional light emitting devices. Here, we report 1300 times enhancement in photoluminescence emission from a MoS2 monolayer via simultaneous Fano resonances in a dielectric photonic crystal. The spatially extended double Fano resonance scheme allows resonant enhancement of both the MoS2 absorption and emission. We also achieve unidirectional emission within a narrow divergence angle of 5 degrees by engineering the Fano resonance angular dispersion. Our approach provides a new platform for efficient light sources with high directionality based on emerging two-dimensional materials. PMID- 28991495 TI - Molecular Dynamics Simulation Study of Polymer Nanocomposites with Controllable Dispersion of Spherical Nanoparticles. AB - Through coarse-grained molecular dynamics simulation, we construct a novel kind of end-linked polymer network by employing dual end-functionalized polymer chains that chemically attach to the surface of nanoparticles (NPs), so that the NPs act as large cross-linkers. We examine the effects of the length and flexibility of polymer chains on the dispersion of NPs, and the effect of the chain length on the stress-strain behavior and the segment orientation during the deformation process. We find that the stress upturn becomes more prominent with the decrease of the chain length, attributed to the limited extensibility of the chain strand connecting two neighboring NPs. In addition, this end-linked polymer nanocomposite (PNC) is shown to have a temperature-dependent stress-strain behavior that is contrary to traditional physically mixed PNCs, whose mechanical properties deteriorate with increasing temperature. This is due to the stability of the dispersion of NPs and higher entropic elasticity at higher temperature for the former, while the latter has poorer interfacial interaction at higher temperature, leading to less reinforcing efficiency. By imposing a dynamic oscillatory shear deformation, we obtain a dynamic hysteresis loop for end-linked and physically mixed dispersions. Interestingly, the end-linked system possesses a much smaller hysteresis loss than does the physically mixed system, with the latter exhibiting a more prominent decrease with increasing temperature, due to less interfacial contact. Our results demonstrate that end-linked PNCs combine attractive static and dynamic mechanical properties and exhibit an unusual response to temperature, which could find potential applications in the future. PMID- 28991496 TI - Bed Bug Bites Limited to Exposed Skin. PMID- 28991497 TI - Polymorphisms of DNA repair genes XRCC1 and LIG4 and idiopathic male infertility. AB - Sperm DNA damage is one of the associated factors of idiopathic male infertility and abnormal spermatogenesis. This study was conducted to assess possible association between risk of male infertility with X-ray repair cross complementing group 1 (XRCC1) Arg399Gln (G to A) and DNA ligase 4 (LIG4) Thr9Ile (C to T) gene polymorphisms which are involved in different DNA repair pathways. In this case-control study 191 fertile and 191 infertile men (29-40 years old) were enrolled. The single-nucleotide polymorphism genotypes and alleles of XRCC1 Arg399Gln and LIG4 Thr9Ile were assessed using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) technique. There was no significant association between XRCC1 Arg399Gln polymorphism and risk of male infertility. The frequency of LIG4 Thr9Ile genotypes and alleles were statistically different between fertile and infertile men (p<0.001). We found that the CT genotype increased infertility risk more than threefold (OR, 3.12; 95% CI, 1.803-5.407). The LIG4 TT genotype carriers had decreased progressive motile sperm (p<0.05) and increased non-progressive motile sperm (p<0.001) compared with the CC genotype. Moreover, sperm concentration in subjects carrying the CT genotype was lower than that observed in CC carriers (p<0.05). The results revealed that the GG/CT and GA/CT combinations of genotypes increase the risk of infertility 3.5 and fourfold, respectively (p=0.021 and 0.004, respectively). This study demonstrated that there was an association between LIG4 Thr9Ile polymorphism and male infertility and suggests CT genotype as a risk factor for male infertility. PMID- 28991498 TI - Spontaneous pneumomediastinum complicating severe acute asthma exacerbation in adult patients. AB - OBJECTIVES: The real incidence of pneumomediastinum (PNM) in adult patients with severe acute asthma exacerbation continues to be unknown. The current study aims to investigate the occurrence of PNM in an adult population of patients presenting a severe asthma attack and to evaluate the risk factors associated to its development. METHODS: The 45 consecutive subjects who were admitted to our Division between January 1, 2015 and December 31, 2016 for severe acute asthma exacerbation underwent a diagnostic protocol including a standard chest X-ray and continuous monitoring of arterial oxygen saturation (SaO2) during the first 24 hours following admission. The patients showing persistence or deterioration of oxyhemoglobin desaturation were prescribed a chest Computed Tomographic (CT) scan. RESULTS: Five out of the 45 patients (11.1%) with severe acute asthma exacerbation were diagnosed with PNM, in one case on the basis of an X-ray image and in four on the basis of a chest CT scan. Data analysis showed that the PNM patients were younger [21 (17-21) vs 49.5 (20-73) yrs; p < 0.001] and more likely to show sensitization to Alternaria (2/5 vs 0/40; p = 0.0101) with respect to their non-PNM counterparts. The duration of hospital stay was similar in the two groups [8 (4-12) vs 7 (3-15) days; p = 0.6939]. CONCLUSIONS: PNM is a common clinical entity in young adults with severe acute asthma exacerbation, particularly in those with unsatisfactory response to initial medical therapy. Although generally benign, patients with suspected PNM should be closely monitored because of the risk of developing severe hypoxemia. PMID- 28991499 TI - Outcome of traumatic brain injury in patients on antiplatelet agents: a retrospective 20-year observational study in a single neurosurgery unit. AB - OBJECTIVE: To evaluate the outcomes after Traumatic Brain Injury (TBI) in patients taking Antiplatelet Agents (APAs). METHODS: We reviewed the clinical records of 934 patients with TBI between 1995 and 2014. Multivariate analysis was performed to correlate patient outcome with various factors, including pre-injury APA intake. Cause of death was compared among groups stratified according to APA dose. RESULTS: Increasing doses of APAs were positively associated with mortality rates, however, differences were primarily due to non-traumatic causes. APA therapy before injury was independent of both overall and non-traumatic mortality. In multivariate analysis, mortality was significantly correlated with the Charlson Comorbidity Index (CCI), pupillary abnormalities, age, Glasgow Coma Scale (GCS), head Abbreviated Injury Scale (AIS) and additional AIS >2. Conversely, non-traumatic mortality was associated with age, GCS, additional AIS >2 and CCI, though only CCI was correlated with increasing APA dose. Furthermore, no significant difference was observed when comparing mortalities according to CCI score among APA groups. Thus, mortalities were associated with the severity of pre-existing conditions rather than APA dose. CONCLUSIONS: The outcome of patients with TBI, who were on APAs may be determined by the severity of pre existing conditions. Aggressive TBI treatment should be implemented when tolerable, regardless of pre-existing APA treatment status. PMID- 28991500 TI - Age estimation based on pulp/tooth volume ratio measured on cone-beam CT images. AB - OBJECTIVES: After tooth eruption, the size of the pulp cavity decreases with age owing to deposition of secondary dentine. The aim of this study was to investigate the relation between the chronological age and the ratio of pulp volume (PV) to tooth volume (TV) measurements using CBCT images of single rooted teeth. METHODS: Maxillary anterior, canine and mandibular canine/premolar CBCT scans of patients older than 15 years of age were collected from the archives between 2013 and 2015 years. Patients with CBCT scans of teeth were seen in detail and patients with known chronological age were included. Teeth with caries, filling or crown restorations, periapical pathologies or pulps that could not be identified were excluded. Consequently, 204 patients with 655 teeth were evaluated. The PV and the TV of each tooth was measured and then the PV/TV ratio was calculated. Simple linear regression analysis was performed in order to predict age estimation by using PV/TV. RESULTS: The PV/TV of all teeth ranged between 0.01 and 0.08. A negative correlation was found between the PV/TV ratio and age (p < 0.05). The regression analysis showed the highest Pearson correlation (0.532) for the maxillary central incisor tooth. Considering measurements of the PV/TV of all assessed teeth, there was no significant difference in the intercept between both gender (p > 0.05). CONCLUSIONS: This study revealed that PV/TV ratio was not gender dependent and the strongest correlation was found between the age and PV/TV ratio measured on maxillary central incisors than other teeth. PMID- 28991501 TI - Ocular Autoimmune Systemic Inflammatory Infectious Study - Report 3: Posterior and Panuveitis. AB - PURPOSE: To report the pattern of posterior and panuveitis at a tertiary referral center in Singapore. METHODS: Subgroup retrospective analysis of 334 new posterior and panuveitis cases, from the Ocular Autoimmune Systemic Inflammatory Infectious Study (OASIS) database. Descriptive analysis was performed and visual outcome and complications were reported. RESULTS: The etiology for posterior uveitis and panuveitis was infectious in 162 patients (48.5%), non-infectious in 144 patients (43.1%), and idiopathic in 28 patients (8.4%). More patients with bilateral disease had a non-infectious etiology (n = 82, 50.9%) (p = 0.012). The most common complication was epiretinal membrane (n = 20, 12.3%) for the infectious group and cystoid macular edema (n = 12, 8.3%) for the non-infectious group. CONCLUSIONS: The proportion of etiologies in our cohort varies from other studies. Understanding the variations and demographic associations allows the diagnosis and management of posterior and panuveitis to be further improved. PMID- 28991502 TI - Sensitivity of Computed Tomography for the Assessment of Spontaneous Dermoid Cyst Localized Rupture with Granulomatous Reaction. AB - PURPOSE: To assess the sensitivity of computed tomography for the diagnosis of spontaneous localized orbital dermoid cyst rupture with granulomatous reaction. METHODS: The charts of 42 patients with dermoid cysts were reviewed retrospectively. The data collected included demographics, clinical features, CT imaging, and postoperative histopathological analysis of the lesions. The association between radiological signs of inflammation and histopathological evidence of an inflammatory reaction was tested by univariate logistic regression. RESULTS: Localized spontaneous rupture with granulomatous reaction occurred in 61.9% of patients. The median age of patients with spontaneous rupture was significantly higher than the age of patients who had no histopathological evidence of rupture. Bone scalloping was significantly associated with preoperative rupture. Fat contents had a protective effect. Large sizes increased the odds of rupture. CONCLUSION: Bone remodeling and histopathological evidence of spontaneous preoperative rupture were significantly associated. Since age, cyst size, and contents are factors contributing to rupture, surgical removal is suggested for dermoids with liquid contents. PMID- 28991503 TI - Current Clinical Application of Microperimetry: A Review. AB - Microperimetry (MP) is a technology that allows the study of retinal sensitivity at different foveal and parafoveal areas as well as eye fixation. It is a technique of functional evaluation, providing a direct correlation between anatomical and functional outcomes. There are a great variety of studies which evaluate the repeatability or reliability of measurements obtained with this technology and also describe and explore different clinical applications. MP has been shown to be useful in the characterization of sensory and motor conditions, such as amblyopia or nystagmus. Concerning ocular pathology, several studies have confirmed the usefulness of MP for evaluating and analyzing different retinal pathological conditions, such as age-related macular degeneration or glaucoma, and for analyzing the effect of different medical or surgical treatments for these conditions. MP has also been shown to be useful for visual training or rehabilitation in some specific cases. PMID- 28991504 TI - Changes in complementarity-determining regions significantly alter IgG binding to the neonatal Fc receptor (FcRn) and pharmacokinetics. AB - A large body of data exists demonstrating that neonatal Fc receptor (FcRn) binding of an IgG via its Fc CH2-CH3 interface trends with the pharmacokinetics (PK) of IgG. We have observed that PK of IgG molecules vary widely, even when they share identical Fc domains. This led us to hypothesize that domains distal from the Fc could contribute to FcRn binding and affect PK. In this study, we explored the role of these IgG domains in altering the affinity between IgG and FcRn. Using a surface plasmon resonance-based assay developed to examine the steady-state binding affinity (KD) of IgG molecules to FcRn, we dissected the contributions of IgG domains in modulating the affinity between FcRn and IgG. Through analysis of a broad collection of therapeutic antibodies containing more than 50 unique IgG molecules, we demonstrated that variable domains, and in particular complementarity-determining regions (CDRs), significantly alter binding affinity to FcRn in vitro. Furthermore, a panel of IgG molecules differing only by 1-5 mutations in CDRs altered binding affinity to FcRn in vitro, by up to 79-fold, and the affinity values correlated with calculated isoelectric point values of both variable domains and CDR-L3. In addition, tighter affinity values trend with faster in vivo clearance of a set of IgG molecules differing only by 1-3 mutations in human FcRn transgenic mice. Understanding the role of CDRs in modulation of IgG affinity to FcRn in vitro and their effect on PK of IgG may have far-reaching implications in the optimization of IgG therapeutics. PMID- 28991505 TI - Modulation of SK channels regulates locomotor alternating bursting activity in the functionally-mature spinal cord. AB - The spinal cord contains specialized groups of cells called pattern generators, which are capable of orchestrating rhythmic firing activity in an isolated preparation. Different patterns of activity could be generated in vitro including right-left alternating bursting and bursting in which both sides are synchronized. The cellular and network mechanisms that enable these behaviors are not fully understood. We have recently shown that Ca2+-activated K+ channels (SK channels) control the initiation and amplitude of synchronized bursting in the spinal cord. It is unclear, however, whether SK channels play a similar role in the alternating rhythmic pattern. In the current study, we used a spinal cord preparation from functionally mature mice capable of weight bearing and walking. The present results extend our previous work and show that SK channel inhibition initiates and modulates the amplitude of alternating bursting. We also show that addition of methoxamine, an alpha1-adrenergic agonist, to a cocktail of serotonin, dopamine, and NMDA evokes robust and consistent alternating bursting throughout the cord. PMID- 28991506 TI - Reproduction Alters Hydration State but Does Not Impact the Positive Effects of Dehydration on Innate Immune Function in Children's Pythons (Antaresia childreni). AB - Resource availability can impact immune function, with the majority of studies of such influences focusing on the allocation of energy investment into immune versus other physiological functions. When energy is a limited resource, performance trade-offs can result, compromising immunity. Dehydration is also considered a physiological challenge resulting from the limitation of a vital resource, yet previous research has found a positive relationship between dehydration and innate immune performance. However, these studies did not examine the effects of dehydration on immunity when there was another concurrent, substantial physiological challenge. Thus, we examined the impact of reproduction and water deprivation, individually and in combination, on immune performance in Children's pythons (Antaresia childreni). We collected blood samples from free ranging A. childreni to evaluate osmolality and innate immune function (lysis, agglutination, bacterial growth inhibition) during the austral dry season, when water availability is limited and this species is typically reproducing. To examine how reproduction and water imbalance, both separately and combined, impact immune function, we used a laboratory-based 2 * 2 experiment. Our results demonstrate that A. childreni experience significant dehydration during the dry season and that, overall, osmolality, regardless of the underlying cause (seasonal rainfall, water deprivation, or reproduction), is positively correlated with increased innate immune performance. PMID- 28991507 TI - A Mountain or a Plateau? Hematological Traits Vary Nonlinearly with Altitude in a Highland Lizard. AB - High-altitude organisms exhibit hematological adaptations to augment blood transport of oxygen. One common mechanism is through increased values of blood traits such as erythrocyte count, hematocrit, and hemoglobin concentration. However, a positive relationship between altitude and blood traits is not observed in all high-altitude systems. To understand how organisms adapt to high altitudes, it is important to document physiological patterns related to hypoxia gradients from a greater variety of species. Here, we present an extensive hematological description for three populations of Sceloporus grammicus living at 2,500, 3,400, and 4,300 m. We did not find a linear increase with altitude for any of the blood traits we measured. Instead, we found nonlinear relationships between altitude and the blood traits erythrocyte number, erythrocyte size, hematocrit, and hemoglobin concentration. Erythrocyte number and hematocrit leveled off as altitude increased, whereas hemoglobin concentration and erythrocyte size were highest at intermediate altitude. Additionally, lizards from our three study populations are similar in blood pH, serum electrolytes, glucose, and lactate. Given that the highest-altitude population did not show the highest levels of the variables we measured, we suggest these lizards may be using different adaptations to cope with hypoxia than lizards at low or intermediate altitudes. We discuss future directions that research could take to investigate such potential adaptations. PMID- 28991508 TI - Responsible decision-making for plant research and breeding innovations in the European Union. AB - Plant research and breeding has made substantial technical progress over the past few decades, indicating a potential for tremendous societal impact. Due to this potential, the development of policies and legislation on plant breeding and the technical progress should preferably involve all relevant stakeholders. However, we argue here that there is a substantial imbalance in the European Union (EU) regarding the influence of the various stakeholder groups on policy makers. We use evidence from three examples in order to show that the role of science is overlooked: 1) important delays in the decision process concerning the authorization of genetically modified (GM) maize events, 2) the significance attributed to non-scientific reasons in new legislation concerning the prohibition of GM events in EU member states, and 3) failure of the European Commission to deliver legal guidance to new plant breeding techniques despite sufficient scientific evidence and advisory reports. We attribute this imbalance to misinformation and misinterpretation of public perceptions and a disproportionate attention to single outlier reports, and we present ideas on how to establish a better stakeholder balance within this field. PMID- 28991510 TI - Firearm-Related Injury and Death - A U.S. Health Care Crisis in Need of Health Care Professionals. PMID- 28991509 TI - Safety testing of monoclonal antibodies in non-human primates: Case studies highlighting their impact on human risk assessment. AB - Monoclonal antibodies (mAbs) are improving the quality of life for patients suffering from serious diseases due to their high specificity for their target and low potential for off-target toxicity. The toxicity of mAbs is primarily driven by their pharmacological activity, and therefore safety testing of these drugs prior to clinical testing is performed in species in which the mAb binds and engages the target to a similar extent to that anticipated in humans. For highly human-specific mAbs, this testing often requires the use of non-human primates (NHPs) as relevant species. It has been argued that the value of these NHP studies is limited because most of the adverse events can be predicted from the knowledge of the target, data from transgenic rodents or target-deficient humans, and other sources. However, many of the mAbs currently in development target novel pathways and may comprise novel scaffolds with multi-functional domains; hence, the pharmacological effects and potential safety risks are less predictable. Here, we present a total of 18 case studies, including some of these novel mAbs, with the aim of interrogating the value of NHP safety studies in human risk assessment. These studies have identified mAb candidate molecules and pharmacological pathways with severe safety risks, leading to candidate or target program termination, as well as highlighting that some pathways with theoretical safety concerns are amenable to safe modulation by mAbs. NHP studies have also informed the rational design of safer drug candidates suitable for human testing and informed human clinical trial design (route, dose and regimen, patient inclusion and exclusion criteria and safety monitoring), further protecting the safety of clinical trial participants. PMID- 28991511 TI - Prevalence of Congenital Ocular Anomalies among Children with Genetic Disorders: An Egyptian Study. AB - PURPOSE: To assess the pattern and frequency of occurrence of ocular anomalies among other genetic disorders in Egypt. METHODS: This is a cross-sectional study of 2500 cases presenting with genetic disorders. Cases were recruited from the clinical genetics department of the National Research Centre (NRC) over a four year period between January 2011 and December 2014. Ophthalmological examination of the cases was performed in the pediatric ophthalmology department of Cairo University Hospitals. RESULTS: Out of 2500 cases with congenital disorders, 2.4% suffered one or more ocular anomalies with a male to female ratio of 1.7:1. Consanguinity was reported in 76.7% and family history was positive in 35% of ocular cases. The most common ocular anomalies were congenital cataract, retinal dystrophies, glaucoma, and retinoblastoma in order of frequency. Chromosomal aberrations were detected in two retinoblastoma cases and in one case of charge association with cataract and iris coloboma. A truncating mutation in exon 8 of OCRL1 was reported in a case of Lowe syndrome with cataract. A total of 51.7% of ocular cases were non-isolated (associated with other genetic disorders). CONCLUSION: In Egypt, ocular genetic disorders are not uncommon among other genetic disorders. Consanguinity is high, suggesting high incidence of autosomal recessive inheritance of genetic disorders with an ocular component. Proper systemic assessment of all cases with ocular anomalies is a necessity due to the high percentage of non-isolated ocular anomalies. Genetic counseling of parents would help in reducing recurrence rates through prenatal diagnosis whenever possible. PMID- 28991512 TI - The Use of the Social Cognition and Object Relations Scale in a Primary Care Setting. AB - Research has indicated that as many as 10% to 15% of primary care patients have symptoms that are not well explained medically. These patients could be labeled as "somatizers." This study assessed the extent to which underlying psychological characteristics contribute to a person's level of somatization and service utilization. The Social Cognition and Object Relations Scale-Global Rating Method (SCORS-G; Stein, Hilsenroth, Slavin-Mulford, & Pinsker, 2011; Westen, 1995) was used to rate early memory narratives of 100 patients in a suburban primary care setting. Using principal axis factoring, the SCORS-G was divided into 2 components and these components (cognitive and affective) were used in subsequent analyses. The affective component was significantly negatively correlated with 2 measures of somatization and positively related to physician ratings of global health. The affective component also showed a trend toward significance on overnight hospital stays and patient-rated health. The cognitive component showed a trend toward significance with both measures of somatization, but it was not correlated with other measures of health. This study demonstrates the value of assessing underlying processes (via SCORS-G ratings of early memory narratives) that contribute to increased rates of somatization and health care utilization. Clinical implications for the relationship between affect and physical health are explored. PMID- 28991513 TI - Long-Term Outcomes in Patients With BRAF V600-Mutant Metastatic Melanoma Who Received Dabrafenib Combined With Trametinib. AB - Purpose To report 5-year landmark analysis efficacy and safety outcomes in patients with BRAF V600-mutant metastatic melanoma (MM) who received BRAF inhibitor dabrafenib (D) and MEK inhibitor trametinib (T) combination therapy versus D monotherapy in the randomized phase II BRF113220 study part C. Patients and Methods BRAF inhibitor-naive patients with BRAF V600-mutant MM were randomly assigned 1:1:1 to receive D 150 mg twice a day, D 150 mg twice a day plus T 1 mg once daily, or D 150 mg twice a day plus T 2 mg once daily (D + T 150/2). Patients who received D monotherapy could cross over to D + T 150/2 postprogression. Efficacy and safety were analyzed 4 and 5 years after initiation in patients with >= 5 years of follow-up. Results As of October 13, 2016, 18 patients who received D + T 150/2 remained in the study (13 [24%] of 54 enrolled at this dose plus five [11%] of 45 initially administered D who crossed over to D + T). With D + T 150/2, overall survival (OS; 4 years, 30%; 5 years, 28%) and progression-free survival (4 and 5 years, both 13%) appeared to stabilize with extended follow-up. Increased OS was observed in patients who received D + T with baseline normal lactate dehydrogenase (5 years, 45%) and normal lactate dehydrogenase with fewer than three organ sites with metastasis (5 years, 51%). With extended follow-up, one additional patient who received D + T 150/2 improved from a partial to a complete response. No new safety signals were observed. Conclusion This 5-year analysis represents the longest follow-up to date with BRAF + MEK inhibitor combination therapy in BRAF V600-mutant MM. Consistent with trends observed in landmark analyses with shorter follow-up, this therapy elicits durable plateaus of long-term OS and progression-free survival that last >= 5 years in some patients with MM. PMID- 28991515 TI - Erratum. PMID- 28991516 TI - Addressing substance use disorder in primary care: The role, integration, and impact of recovery coaches. AB - BACKGROUND: Only 10% of people with substance use disorder (SUD) receive treatment, partially due to inadequate access to specialty SUD care and limited management within primary care. "Recovery coaches" (RCs), peers sharing the lived experience of addiction and recovery, are increasingly being integrated into primary care to help reach and treat people experiencing SUD, yet little is known about how their role should be defined or about their clinical integration and impact. METHODS: Semistructured interviews with RCs (n = 5) and their patients (n = 16) were used to explore patient and RC perspectives on the RC role. Maximum variation sampling was employed to select patients who displayed diversity across gender, RC, housing status, and number of contacts with an RC. Patients were sampled until no new concepts emerged from additional interviews, and a semistructured interview guide was used for data collection. To analyze interview transcripts, the constant comparative method was used to develop and assign inductively developed codes. Two coders separately coded all transcripts and reconciled code assignments. RESULTS: Four core RC activities were identified: system navigation, supporting behavior change, harm reduction, and relationship building. Across these activities, benefits of the RC role emerged, including accessibility, shared experiences, motivation of behavior change, and links to social services. Challenges of the RC model were also evident: patient discomfort with asking for help, lack of clarity in RC role, and tension within the care team. CONCLUSIONS: These findings shed light on RCs in primary care. Many patients and coaches perceived that RCs play a valuable role within primary care, providing both tangible system navigation and intangible, social support that promote recovery and might not otherwise be available. Enhanced communication between RCs and health center leadership in defining the RC role may help resolve ambiguity and related tensions between RCs and care team members. PMID- 28991514 TI - Dacryocystectomy: Indications and Results at Tertiary Eye Hospital in Central Saudi Arabia. AB - PURPOSE: To report indications and success rates of dacryocystectomy (DCT) in a tertiary hospital. METHODS: A retrospective chart review was performed of all patients who underwent DCT at the King Khaled Eye Specialist Hospital, Saudi Arabia, from 2008 to 2015. Data included patient demographics, symptoms before and after surgery, and complications. Univariate analysis using parametric and non-parametric methods was performed. RESULTS: Forty-seven DCT surgeries were performed over the study period. The median age of patients was 58.2 +/- 2 years old, 63.8% were female, 60% of surgeries were performed on the left side, and 8% of patients underwent bilateral simultaneous DCT. Chronic dacryocystitis was the surgical indication for DCT for all of the patients and 23.5% of them had dry eye preoperatively. Successful treatment was observed in 80.8% of patients and 8.5% complained of tearing after DCT. CONCLUSION: The main indication for DCT in our hospital was chronic dacryocystitis with good outcomes for elderly patients with dry eyes. PMID- 28991518 TI - Hospice Care: Nurses' Experience and Perception of Older Adult Patients' Experience. AB - OBJECTIVES: The current study sought to understand the differences hospice nurses perceived in caring for older adult patients who utilize hospice for longer and shorter periods, older adult patients' experience of hospice services, and if length of hospice stays influenced the patients' end-of-life experience. METHODS: Interpretative Phenomenological Analysis was used to extract themes and subthemes from 10 interviews conducted with hospice nursing staff. RESULTS: Four major themes were identified pertaining to nurses perspective on older adults' views of hospice and how length of hospice use impacts end-of-life care. CONCLUSION: These themes suggest hospice nursing staff believe longer hospice stays are more positive and that older adults identify more positive aspects of hospice when using it for longer periods of time. Results suggest that nurses believe length of use directly impacts patient care and the experience of hospice services. CLINICAL IMPLICATIONS: Participating nurses reported that older adults have a lack of information on hospice services. It was suggested that more information is needed and that providing such education may lead to longer hospice stays. PMID- 28991519 TI - Association between binge drug use and suicide attempt among people who inject drugs. AB - BACKGROUND: People who inject drugs (PWID) have an elevated risk of suicide attempt. Although different substances are associated with suicide attempt, the overall risk posed by binge behavior, a high-risk pattern of drug use, remains unclear. The objective of this study is to assess the association between binge drug use and suicide attempt in a prospective cohort of PWID in Montreal, Canada. METHODS: Participants answered a biannual interviewer-administered questionnaire compiling information on sociodemographics, pattern of substance use (cocaine, amphetamine, opioids, sedative-hypnotics, alcohol, and cannabis), and psychosocial stressors and related markers. The relationship between suicide attempt and binge behavior was modeled using generalized estimating equations (GEEs), controlling for type and pattern of substance use, sociodemographic characteristics, and significant mental health markers. RESULTS: Among 1240 participants (mean age +/- SD: 38.2 +/- 9.8) at baseline, 222 (17.9%) reported binge during the past 6-months. PWID reporting binge were significantly younger (P < .001), less educated (P = .012), less likely male (P = .047), and had shorter history of injection (P < .001). In addition, they were younger at first injection (P = .014), reported higher rates of prostitution and psychological disorders (P = .003), and were more likely to use other drugs except cannabis and alcohol. Binge was independently associated with attempted suicide in the GEE multivariate model (adjusted odds ratio [aOR 95% CI] = 1.91 [1.38-2.65], P < .001). CONCLUSIONS: Among PWID at high risk of suicide attempt, those who binge represent a particularly vulnerable subgroup. Although the exact mechanisms underlying this finding remain unresolved, several hypothesis pertaining to the neurobiological and psychosocial consequences of binge, as well as common personality traits, warrant further investigations. PMID- 28991520 TI - Mortality risk in a sample of emergency department patients who use cocaine with alcohol and/or cannabis. AB - BACKGROUND: Illicit drug use is common among emergency department (ED) patients, yet the association between drug use and subsequent mortality is not well understood. This study examines 36-month mortality rates for a sample of ED patients based on reported use of alcohol, cannabis, and cocaine, both individually and in combination. METHODS: Patients (N = 1669) from 2 urban EDs were surveyed at the time of the visit. The patient survey included the Alcohol Smoking and Substance Involvement Screening Test (ASSIST) and information on physical and mental health, health care utilization, and risk factors associated with substance use. ASSIST scores were used to categorize patients into drug risk groups. Mortality information from the National Death Index was used to calculate mortality rates from 2009 to 2012. A Cox regression model identified associations between drug risk groups and mortality while controlling for patient demographics. RESULTS: The use of cocaine and cannabis both individually and in combination was associated with significantly higher mortality risk compared with other ED patients. CONCLUSIONS: ED patients who use cannabis and cocaine have higher mortality risks than other patients. Further research is necessary to determine whether this result is stable across racial/ethnic groups. PMID- 28991521 TI - Exploring the bilingual advantage: manipulations of similarity and second language immersion in a Stroop task. AB - To explain varying previous results as to whether bilinguals show an advantage over monolinguals in inhibitory control, two hypotheses have been suggested. The Bilingual Inhibitory Control Advantage (BICA) hypothesis proposes a bilingual advantage specific to the presence of conflict. In contrast, the Bilingual Executive Processing Advantage (BEPA) hypothesis proposes a global advantage in processing, across all contexts. The present research contrasts these hypotheses by investigating the effects of second language immersion and similarity of colour terms across languages on the bilingual Stroop task. Ten English and ten German native speakers, residing in Munich, Germany, completed a bilingual Stroop task using stimuli with colour terms which were similar or dissimilar between the two languages. Event-related potentials were recorded alongside behavioural data. Dissimilar stimuli showed greater costs, reflected by increased reaction times (RTs), more negative N400 amplitudes and more positive Late Positive Component (LPC) amplitudes, than similar stimuli. Participants who were immersed in a second language environment experienced greater costs, which were specific to conflict trials for RT and LPC measures, but occurred across all trial types during the N400 window. It was concluded that in contrast to previous research only supporting BEPA, there is also evidence for the BICA hypothesis. PMID- 28991522 TI - Heterogeneity of state medical marijuana laws and adolescent recent use of alcohol and marijuana: Analysis of 45 states, 1991-2011. AB - OBJECTIVE: To assess associations between enactment of state medical marijuana laws (MMLs), MML restrictiveness, and past-30-day youth alcohol use overall, and in relation to marijuana use. METHOD: This quasi-experimental difference-in difference designed study used state-level Youth Risk Behavior Survey data of 9th 12th grade students in 45 states from 1991-2011 (N = 715,014). We conducted bivariate (unadjusted) and multivariable (adjusted for state, year, individual characteristics) logistic regression analyses to examine the effect of MML enactment (yes/no) and less restrictive vs. more restrictive MMLs on five varying measures of past 30-day alcohol use (i.e., any use or binge) and alcohol and marijuana use behaviors. RESULTS: In the final adjusted analyses, MML enactment was associated with lower odds of adolescent past 30-day (1) alcohol use (OR = 0.92, [0.87, 0.97], p < .01) and (2) use of both alcohol and marijuana (OR = 0.93, [0.87, 0.99], p < .05). States with less restrictive MMLs had lower odds of past 30-day (1) alcohol use (OR = 0.94, [0.92, 0.97], p < .001), (2) binge drinking (OR = 0.96, [0.93, 0.97], p < .05), (3) alcohol use without any marijuana use (OR = 0.96, [0.93, 0.99], p < .01), and (4) use of both alcohol and marijuana (OR = 0.96, [0.92, 0.99], p < .05). CONCLUSIONS: This study found that enactment of any MML, and of less restrictive MMLs, was associated with lower odds of past 30-day adolescent alcohol use among adolescents. With continued change in state marijuana laws, it is important to monitor the effect of their enactment and implementation, as well as their specific provisions (e.g. dispensaries, home cultivation), which may differentially affect adolescent behaviors. PMID- 28991523 TI - The LSS Cohort of Atomic Bomb Survivors and LNT. Comments on ''Solid Cancer Incidence among the Life Span Study of Atomic Bomb Survivors: 1958-2009" (Radiat Res 2017; 187:513-37) and "Reply to the Comments by Mortazavi and Doss" (Radiat Res 2017; 188:369-71). PMID- 28991524 TI - Comments on "Cellular Therapies for Treatment of Radiation Injury after a Mass Casualty Incident" (Radiat Res 2017; 188:242-45). PMID- 28991525 TI - Research advances in the treatment of Alzheimer's disease with polysaccharides from traditional Chinese medicine. AB - Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the loss of patients' memory and their cognitive abilities and the mechanism is not completely clear. Although a variety of drugs have been approved for the AD treatment, substances which can prevent and cure AD are still in great need. The effect of polysaccharides from traditional Chinese medicine (TCM) on anti-AD has gained great progress and attained more and more attention in recent years. In this review, research advances in TCM-polysaccharides on AD made in this decade are summarized. PMID- 28991526 TI - Advance in quality assessment of Chinese materia medica using microscopic and morphological methods. AB - Quality evaluation plays a vital role in ensuring safety and effectiveness of Chinese materia medica (CMM). Microscopic and morphological technologies can be used to distinguish CMM's characteristics, such as shape, size, texture, section, and smell, for authenticity and quality control of CMM. The microscopic and morphological applications of novel micro-technology, colorimeter, and texture analyzer for CMM identification are summarized and the future prospect is discussed in this paper. Various styles and complex sources of CMM are systemically reviewed, including cormophyte medicinal materials, fruit and seeds, pollen grain, and spore materials. PMID- 28991527 TI - Mangiferin ameliorates insulin resistance by inhibiting inflammation and regulatiing adipokine expression in adipocytes under hypoxic condition. AB - Adipose tissue hypoxia has been recognized as the initiation of insulin resistance syndromes. The aim of the present study was to investigate the effects of mangiferin on the insulin signaling pathway and explore whether mangiferin could ameliorate insulin resistance caused by hypoxia in adipose tissue. Differentiated 3T3-L1 adipocytes were incubated under normal and hypoxic conditions, respectively. Protein expressions were analyzed by Western blotting. Inflammatory cytokines and HIF-1-dependent genes were tested by ELISA and q-PCR, respectively. The glucose uptake was detected by fluorescence microscopy. HIF 1alpha was abundantly expressed during 8 h of hypoxic incubation. Inflammatory reaction was activated by up-regulated NF-kappaB phosphorylation and released cytokines like IL-6 and TNF-alpha. Glucose uptake was inhibited and insulin signaling pathway was damaged as well. Mangiferin substantially inhibited the expression of HIF-1alpha. Lactate acid and lipolysis, products released by glycometabolism and lipolysis, were also inhibited. The expression of inflammatory cytokines was significantly reduced and the damaged insulin signaling pathway was restored to proper functional level. The glucose uptake of hypoxic adipocytes was promoted and the dysfunction of adipocytes was relieved. These results showed that mangiferin could not only improve the damaged insulin signaling pathway in hypoxic adipocytes, but also ameliorate inflammatory reaction and insulin resistance caused by hypoxia. PMID- 28991528 TI - Protosappanin A exerts anti-neuroinflammatory effect by inhibiting JAK2-STAT3 pathway in lipopolysaccharide-induced BV2 microglia. AB - Microglial activation and resultant neuroinflammatory response are implicated in various brain diseases including Alzheimer's disease and Parkinson's disease. Treatment with anti-neuroinflammatory agents could provide therapeutic benefits for such disorders. Protosappanin A (PTA) is a major bioactive ingredient isolated from Caesalpinia sappan L.. In this work, the anti-neuroinflammatory effects of PTA on LPS-stimulated BV2 cells were investigated and the underlying mechanisms were explored. Results showed that PTA significantly inhibited the production of TNF-alpha and IL-1beta in LPS-activated BV2 microglia. Moreover, the mRNA expressions of IL-6, IL-1beta, and MCP-1 were reduced by PTA in a dose dependent manner. Furthermore, PTA suppressed JAK2/STAT3-dependent inflammation pathway through down-regulating the phosphorylation of JAK2 and STAT3, as well as STAT3 nuclear translocation against LPS treatment. These observations suggested a novel role for PTA in regulating LPS-induced neuroinflammatory injuries. PMID- 28991529 TI - Two new phragmalin-type limonoids orthoesters from Entandrophragma candollei. AB - Two new phragmalin-type limonoids orthoesters, encandollens A and B (1 and 2), were isolated from the stem barks of Entandrophragma candollei collected in Ghana. The structures of these compounds were elucidated on the basis of HR-ESI MS, 1H and 13C NMR, HSQC, HMBC, and ROESY data. Compound 1 was a rare C-15 enolic acyl phragmalin-type limonoid orthoester. Compounds 1 and 2 exhibited weak inhibitory effects on NO production in lipopolysaccharide (LPS)-induced RAW 264.7 cells. PMID- 28991530 TI - Combination of LC/MS and GC/MS based metabolomics to study the hepatotoxic effect of realgar nanoparticles in rats. AB - Realgar nanoparticles (NPs) are increasingly used as therapeutic agents for their enhanced anti-proliferation effect and cytotoxicity on cancer cells. However, the alteration of particle size may enhance biological reactivity as well as toxicity. A LC/MS and GC/MS based metabolomics approach was employed to explore the mechanism of realgar NPs-induced hepatotoxicity and identify potential biomarkers. Male Sprague-Dawley rats were administrated intragastrically with realgar or realgar NPs at a dose of 1.0 g.kg-1.d-1 for 28 days and toxic effects of realgar NPs on liver tissues were examined by biochemical indicator analysis and histopathologic examination. Increased levels of serum enzymes and high hepatic steatosis were discovered in the realgar NPs treated group. Multivariate data analysis revealed that rats with realgar NPs-induced hepatotoxicity could be distinctively differentiated from the animals in the control and realgar treated groups. In addition, 21 and 32 endogenous metabolites were apparently changed in the serum and live extracts, respectively. Realgar NPs might induce free fatty acid and triglyceride accumulation, resulting in hepatotoxicity. In conclusion, the present study represents the first comprehensive LC/MS- and GC/MS-based metabolomics analysis of realgar NPs-induced hepatotoxicity, which may help further research of nanotoxicity. PMID- 28991531 TI - Identification of human cytochrome P450 and UGT enzymes involved in the metabolism of ferulic acid, a major bioactive component in traditional Chinese medicines. AB - Ferulic acid (FA) is an active component of herbal medicines. One of the best documented activities of FA is its antioxidant property. Moreover, FA exerts antiallergic, anti-inflammatory, and hepatoprotective effects. However, the metabolic pathways of FA in humans remain unclear. To identify whether human CYP or UGT enzymes are involved in the metabolism of FA, reaction phenotyping of FA was conducted using major CYP-selective chemical inhibitors together with individual CYP and UGT Supersomes. The CYP- and/or UGT-mediated metabolism kinetics were examined simultaneously or individually. Relative activity factor and total normalized rate approaches were used to assess the relative contributions of each major human CYPs towards the FA metabolism. Incubations of FA with human liver microsomes (HLM) displayed NADPH- and UDPGA-dependent metabolism with multiple CYP and UGT isoforms involved. CYPs and UGTs contributed equally to the metabolism of FA in HLM. Although CYP1A2 and CYP3A4 appeared to be the major contributors in the CYP-mediated clearance, their contributions to the overall clearance are still minor (< 25%). As a constitute of many food and herbs, FA poses low drug-drug interaction risk when co-administrated with other herbs or conventional medicines because multiple phase I and phase II enzymes are involved in its metabolism. PMID- 28991532 TI - A new approach for identification of medicinal almonds by fourier transform infrared spectroscopy and systematic clustering of characteristic peaks. AB - Medicinal almonds have been used for over 2 000 years and its clinical efficacy includes relieving cough and asthma. The domestic market in China is flooded with different kinds of dried almonds, such as bitter almond (Armeniacae Semen Amarum, AAS), sweet almond (Armeniacae Semen Dulce, ADS), salted almond (Armeniacae Semen Salsa, ASS), and their sulfur-fumigating products (Armeniacae Semen Sulphur Fumabat, ASFS). Wide varieties of almonds may lead to uncertain efficacy, aberrant quality, and even increased safety risk. However, the authentication method for medicinal almonds has not been reported, although imposters may lead to ineffective medical response. In the present study, Fourier transform infrared spectroscopy (FTIR) and the 2-dimensional infrared (2D-IR) spectroscopy were used to identify different almonds, which were extracted with different solvents including water, methanol, ethanol, chloroform and ethyl acetate, respectively. A new simple FTIR method was developed in the present study. According to the gradient solvent polarity, a new 2D IR method was first developed, and the commodities of almonds in China were analyzed by using the FTIR spectroscopy supported by hierarchical clustering of characteristic peaks. Moreover, 5 hydroxymethyl-2-furfural could be used as a detection index and control target in the quality control of medicinal almonds. PMID- 28991533 TI - An UHPLC-MS/MS method for simultaneous determination of quercetin 3-O-rutinoside, kaempferol 3-O-rutinoside, isorhamnetin 3-O-rutinoside, bilobalide and ligustrazine in rat plasma, and its application to pharmacokinetic study of Xingxiong injection. AB - The present study was designed to develop and validate a rapid, sensitive, and reliable ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) method for the simultaneous determination of five major active constituents in the traditional Chinese medicinal preparation Xingxiong injection (XXI) in rat plasma, including quercetin 3-O-rutinoside (QCR), kaempferol 3-O-rutinoside (KFR), isorhamnetin 3-O-rutinoside (ISR), bilobalide (BB), and ligustrazine (LGT). The plasma samples were pretreated by protein precipitation with acetonitrile. The chromatographic separation was achieved on a Waters Symmetry C18 analytical column (2.1 mm * 100 mm, 3.5 MUm) with a mobile phase of 0.1% aqueous formic acid (A)-acetonitrile (B). Quantitation of the five bioactive constituents was achieved. Naringin was used as the internal standard (IS). All the calibration curves showed good linearity (r > 0.996) over the concentration range, with the lowest limit of quantification (LLOQ) between 2-18 ng.mL-1. The intra- and inter-day accuracy and precision of the analytes were both within acceptable limits. Moreover, satisfactory extraction recoveries (90.92%-104.03%) were obtained by protein precipitation. The validated method was successfully applied to a pharmacokinetic study of XXI in rats after intravenous administration at three doses. The pharmacokinetic parameters of the five compounds varied in a dose-dependent manner within the tested dosage range. The present study was the first report of pharmacokinetic study for XXI. PMID- 28991534 TI - Another CARE Act. PMID- 28991535 TI - Is it time for a magnetic resonance imaging-targeted only prostate biopsy strategy? PMID- 28991536 TI - Acute ischemic gastric ulcer. PMID- 28991537 TI - Corrigendum to High load hepatitis B virus replication inhibits hepatocellular carcinoma cell metastasis through regulation of epithelial-mesenchymal transition: International Journal of Infectious Diseases [20 (2014)] 37-41. PMID- 28991538 TI - Environmental management as a pillar for sustainable development. AB - There is a growing concern about how to minimize the impact of human activities on the environment. Already nowadays, in some places adaptation efforts are needed in order to avoid the irreversibility of negative human activities. Due to climate changes, and corresponding environmental and social changes, there is a great need for a more sustainable development of mankind. Over the years, research studies that analyzed the sustainable development of different communities with a multi-disciplinary approach, stressed the necessity of preserving the environment for next generations. Therefore, responsible and conscientious management of the environment is a pillar of the sustainable development concept. This review introduction article provides an overview of the recent top scientific publications related to sustainable development that mostly originated from previous SDEWES conferences. PMID- 28991539 TI - Should the Ramped Position Be "Sniffed at" in the ICU? PMID- 28991540 TI - Sex Differences in the Risk of Incident Hypertension With Sleep Apnea: Does Postmenopausal Status Matter? PMID- 28991541 TI - COPD National Action Plan: Addressing a Public Health Need Together. PMID- 28991542 TI - GUNS AND KNIVES. PMID- 28991543 TI - Potential Mechanisms of Microbial Pathogens in Idiopathic Interstitial Lung Disease. PMID- 28991544 TI - Response. PMID- 28991545 TI - Can Meta-Analysis Provide an Exact Comparison of Video and Direct Laryngoscopes for Intubation in Patients in the ICU? PMID- 28991546 TI - Response. PMID- 28991547 TI - Nonconsensual Determination of Neurologic (Brain) Death: Is It a Violation of Constitutional Rights? PMID- 28991548 TI - Response. PMID- 28991549 TI - Vitamin C and Sepsis: Framing the Postpublication Discussion. PMID- 28991550 TI - Response. PMID- 28991551 TI - Intravenous Immunoglobulin for Heparin-Induced Thrombocytopenia. PMID- 28991553 TI - A 71-Year-Old Woman Presenting With Abdominal Pain and Dyspnea. PMID- 28991552 TI - A Platelet Factor 4-Dependent Platelet Activation Assay Facilitates Early Detection of Pathogenic Heparin-Induced Thrombocytopenia Antibodies. AB - Heparin-induced thrombocytopenia (HIT) is a dangerous complication of heparin therapy. HIT diagnosis is established by recognizing thrombocytopenia and/or thrombosis in an affected patient and from the results of serological tests such as the platelet factor 4 (PF4)/heparin immunoassay (PF4 ELISA) and serotonin release assay (SRA). Recent studies suggest that HIT antibodies activate platelets by recognizing PF4 in a complex with platelet glycosaminoglycans (and/or polyphosphates) and that an assay based on this principle, the PF4 dependent P-selectin expression assay (PEA), may be even more accurate than the SRA for HIT diagnosis. Here, we demonstrate that the PEA detected pathogenic antibodies before the SRA became positive in two patients with HIT studied serially, in one case even before seropositivity in the PF4 ELISA. In one of the patients treated with plasma exchange, persistent dissociation between the PEA and SRA test results was observed. These results support a role for the PEA in early HIT diagnosis. PMID- 28991554 TI - A 17-Year-Old Male Adolescent With Shortness of Breath, Fever, and Right Pleuritic Chest Pain. PMID- 28991555 TI - A 63-Year-Old Woman With Neurofibromatosis Type 1 and Pulmonary Hypertension With Worsening Hypoxemia. AB - CASE PRESENTATION: A 63-year-old woman with a history of neurofibromatosis type-1 (NF-1) and pulmonary arterial hypertension (PAH) thought to be secondary to the NF-1 presented with a few weeks of worsening dyspnea on exertion. She took no medications other than sildenafil for her pulmonary hypertension (PH). She denied tobacco, alcohol, and illicit or anorectic drug use. She had previously worked as a waitress. Her mother and her brother had NF-1 but no PH or lung disease. PMID- 28991556 TI - A 58-Year-Old Woman With Pneumonia and Gram-Negative Diplococci. AB - CASE PRESENTATION: A 58-year-old woman with COPD, cor pulmonale, diabetes, and hypertension had a productive cough of greenish and purulent sputum, low-grade fever, and shortness of breath. Medications were metformin, losartan, cholecalciferol, folic acid, a multivitamin, fluticasone by inhalation, and, as needed, ipratropium by inhalation. She lived alone and worked as a physician, had received that year's seasonal influenza vaccine, was a heavy smoker, did not drink alcohol or use illicit drugs, and had no personal or family history of allergy and autoimmunity. PMID- 28991557 TI - Screening for Breast Cancer. AB - The goal of screening is to detect breast cancers when still curable to decrease breast cancer-specific mortality. Breast cancer screening in the United States is routinely performed with mammography, supplemental digital breast tomosynthesis, ultrasound, and/or MR imaging. This article aims to review the most commonly used breast imaging modalities for screening, discuss how often and when to begin screening with specific imaging modalities, and examine the pros and cons of screening. By the article's end, the reader will be better equipped to have informed discussions with patients and medical professionals regarding the benefits and disadvantages of breast cancer screening. PMID- 28991558 TI - Lung Cancer Screening: Why, When, and How? AB - This article explains the rationale of lung cancer screening with low-dose computed tomography and provides a practical approach to all relevant aspects of a lung cancer screening program. Imaging protocols, patient eligibility criteria, facility readiness, and reimbursement criteria are addressed step by step. Diagnostic criteria and Lung-RADS (Lung Computed Tomography Screening Reporting and Data System) nodule management pathways are illustrated with examples. Pearls and pitfalls for interpretation of lung cancer screening low-dose chest computed tomography are discussed. PMID- 28991559 TI - Imaging and Screening for Colorectal Cancer with CT Colonography. AB - Despite being readily preventable, colorectal cancer ranks second behind only lung cancer in overall mortality. However, this situation could be reversed if screening tests that effectively detect advanced adenomas and early cancers were broadly applied. Computed tomographic colonography (CTC) reflects an ideal balance of minimal invasiveness with high-level performance, assuming all facets of the examination are appropriately addressed. Unfortunately, this promising screening test remains grossly underused. This article details the technical and interpretive approaches used by one successful CTC screening program. PMID- 28991560 TI - Screening and Surveillance of Hepatocellular Carcinoma: An Introduction to Ultrasound Liver Imaging Reporting and Data System. AB - Given the high prevalence, increasing incidence, and significant morbidity and mortality related to hepatocellular carcinoma (HCC), a robust and cost-effective screening and surveillance program is needed. Most societies recommend ultrasound for HCC screening, despite lack of standardization in imaging acquisition, reporting content and language, and follow-up recommendations. The American College of Radiology Ultrasound Liver Imaging Reporting and Data System (US LI RADS) fills this unmet need by providing standardization in the use of US in at risk patients. It is anticipated that US LI-RADS will improve the performance of ultrasound for HCC screening and surveillance and unify management recommendations. PMID- 28991561 TI - Imaging and Screening of Cancer of the Gallbladder and Bile Ducts. AB - Biliary cancers include gallbladder cancer (GBC) and cholangiocarcinoma (CCA). GBC may appear as a mass replacing the gallbladder, thickened gallbladder wall, or polypoid lesion in the gallbladder. Gallbladder polyps with low risk of GBC (eg, 6- to 10-mm polyps without other risk factors) are screened with sonography. In general, polyps smaller than 5 mm are ignored and those larger than 10 mm require surgical consideration. Screening for CCA is less well-established. On imaging, CCA may be divided into mass-forming, periductal infiltrating, and intraductal types. This review discusses the current state of screening and diagnosis of GBC and CCA. PMID- 28991562 TI - Imaging and Screening of Pancreatic Cancer. AB - Given the low disease prevalence of both exocrine and endocrine cancers in the general population, screening is not recommended. However, in as many as 25% of cases there is a precursor lesion or an identifiable genetic predisposition. For these patients at increased risk, screening with imaging is recommended. Multidetector computed tomography, MR imaging or magnetic resonance cholangiopancreatography, and endoscopic ultrasound examination can be used as screening modalities. Recent advances in dual energy CT and total body MR imaging have increased the suitability of these noninvasive modalities as first-line imaging screening options. PMID- 28991564 TI - Imaging and Screening of Ovarian Cancer. AB - Ovarian cancer has a high mortality, attributed to its typically advanced stage at detection. Despite much effort to identify an effective approach for ovarian cancer screening, to date no screening test has proven to reduce ovarian cancer mortality. The natural history of ovarian cancer is reviewed as well as data from the largest trials of ovarian cancer screening. Currently, no North American society recommends routine ovarian cancer screening; some societies recommend consideration of screening with pelvic ultrasound and CA-125 in women at high risk, although its use in this setting is not supported by data demonstrating a mortality benefit. PMID- 28991565 TI - Imaging and Screening of Thyroid Cancer. AB - Ultrasound is the first-line diagnostic tool for diagnosis of thyroid diseases. The low aggressiveness of many thyroid cancers coupled with high sensitivity of sonography can lead to cancer diagnosis and treatment with no effect on outcomes. Ultrasound is recognized as the most important driver of thyroid cancer overdiagnosis. Ultrasound should not be used as a general screening tool and should be reserved for patients at high risk of thyroid cancer and in the diagnostic management of incidentally discovered thyroid nodules. With prescreening risk stratification and application of consensus criteria for nodule biopsy, the value of the diagnostic ultrasound can be maximized. PMID- 28991563 TI - Imaging and Screening of Kidney Cancer. AB - Renal cell carcinoma (RCC) exhibits a diverse and heterogeneous disease spectrum, but insight into its molecular biology has provided an improved understanding of potential risk factors, oncologic behavior, and imaging features. Computed tomography (CT) and MR imaging may allow the identification and preoperative subtyping of RCC and assessment of a response to various therapies. Active surveillance is a viable management option in some patients and has provided further insight into the natural history of RCC, including the favorable prognosis of cystic neoplasms. This article reviews CT and MR imaging in RCC and the role of screening in selected high-risk populations. PMID- 28991566 TI - Imaging and Screening of Cancer of the Small Bowel. AB - Delayed diagnosis of small bowel cancers frequently occurs and may arise because of many factors, including low incidence of disease, difficult endoscopic access, lack of mucosal mass or abnormality, subtle radiologic features, and low index of clinical suspicion. As small bowel cancers are rare and their causes are largely unknown, routine population-based screening of asymptomatic patients to find precursor lesions or early cancers is ineffective. However, targeted screening/surveillance strategies are used in specific at-risk and symptomatic patient populations. This article reviews issues regarding early diagnosis of small bowel cancers, with focus on state-of-the-art cross-sectional imaging techniques. PMID- 28991568 TI - Imaging and Cancer Screening. PMID- 28991567 TI - Imaging and Screening of Hereditary Cancer Syndromes. AB - There is a wide spectrum of mendelian disorders that predispose patients to an increased risk of benign as well as malignant tumors. Hereditary cancer syndromes are characterized by the early onset of diverse, frequently advanced malignancies in specific organ systems in multiple family members, posing significant challenges to diagnosis and management. A better understanding of the genetic abnormalities and pathophysiology that underlie these disorders has led to contemporary paradigms to screen, allowing early diagnosis, and has improved targeted therapies to aid in management. This article reviews select hereditary cancer syndromes with an emphasis on imaging-based screening and surveillance strategies. PMID- 28991569 TI - Changing Priorities in Critical Care? PMID- 28991570 TI - Diagnostic Wrist Arthroscopy. AB - After reviewing this article, readers should have a comprehensive understanding of the indications for diagnostic arthroscopy, technical considerations in performing a systematic evaluation of the wrist, and limitations of this technique. PMID- 28991571 TI - Wrist Arthroscopy Under Portal Site Local Anesthesia Without Tourniquet and Sedation. AB - We had developed the technique of portal site local anaesthesia (PSLA) for wrist arthroscopy. Two percent lidocaine with 1:200,000 epinephrine is injected through a 25G needle to various portal sites. The radiocarpal joint is then distended with saline injection and portal is created with transverse superficial skin incision followed by dilation with curved hemostat. The patient is neither sedated, nor under general or regional anaesthesia. Tourniquet is not routinely used. PSLA can achieve satisfactory comfort level in 88% of our 111 patients without any complication. In well-selected patients, it is a safe and comfortable procedure. PMID- 28991573 TI - Arthroscopic Management of Triangular Fibrocartilage Complex Peripheral Injury. AB - Patients suffering from ulnar-sided wrist pain after trauma may develop tenderness, clicking, a positive fovea sign, or instability of the distal radioulnar joint. If the pain is persistent, conservative treatment does not help, and the patient agrees to surgery, arthroscopy may reveal a triangular fibrocartilage complex (TFCC) injury with capsular detachment, foveal avulsion, or a combination thereof. Capsular reattachment is possible using an arthroscopic assisted technique. The reattachment can be performed with an inside-out, outside in, or all-inside technique, providing good to excellent results, which tend to persist over time, in 60% to 90% of cases. PMID- 28991572 TI - Chronologic and Geographic Trends of Triangular Fibrocartilage Complex Repair. AB - This article shows trends in triangular fibrocartilage complex (TFCC) repair since 1990 by geographic area and year. The repair methods presented in the literature were inside-out, outside-in, all-inside, and open repair. The outside in technique was reported most often for ulnar-side tears, whereas the inside-out technique was reported most frequently for radial-side tears. Recently, a foveal reattachment technique for ulnar-side tears has garnered attention and has been reported with increasing frequency, especially in Asia, because the deepest portion of TFCC, attached to fovea, plays a key role in stabilizing the distal radioulnar joint. Understanding these trends can help clinicians best treat TFCC tears. PMID- 28991574 TI - Arthroscopic Management of Triangular Fibrocartilage Complex Foveal Injury. AB - The deep component of triangular fibrocartilage complex (TFCC) inserts onto the fovea of the ulnar head. This component is critical to provide distal radioulnar joint stability. The surgical techniques and results of transosseous inside-out TFCC foveal repair are discussed. The rewarding results encouraged the repair of TFCC to the fovea arthroscopically. Although the results are good, the factors of age (traumatic or degenerative) and quality of stump and TFCC proper, which relate to the results should be considered in the future. PMID- 28991576 TI - Arthroscopic Management of Ulnocarpal Impaction Syndrome and Ulnar Styloid Impaction Syndrome. AB - Both ulnocarpal impaction syndrome and ulnar styloid impaction syndrome can produce ulnar wrist pain. The definition and clinical differentiation are explained. The relevant anatomy, biomechanics, causes, diagnosis, and arthroscopic treatments, as well as the surgical indications, techniques, and outcomes of these syndromes are discussed in detail. PMID- 28991575 TI - Arthroscopic-Assisted Triangular Fibrocartilage Complex Reconstruction. AB - Injury of the triangular fibrocartilage complex (TFCC) is a common cause of ulnar sided wrist pain. Volar and dorsal radioulnar ligaments and their foveal insertion are the most important stabilizing components of the TFCC. In irreparable tears, anatomic reconstruction of the TFCC aims to restore normal biomechanics and stability of the distal radioulnar joint. We proposed a novel arthroscopic-assisted technique using a palmaris longus tendon graft. Arthroscopic-assisted TFCC reconstruction is a safe and effective approach with outcomes comparable to conventional open reconstruction and may result in a better range of motion from minimizing soft tissue dissection and subsequent scarring. PMID- 28991577 TI - Arthroscopic Evaluation of Associated Soft Tissue Injuries in Distal Radius Fractures. AB - The best outcome in distal radius fractures is achieved if anatomy is restored, in particular the intra-articular congruity. This is achieved partly with improved fixation, such as using volar locking plates, and partly by using an arthroscopy-assisted reduction and fixation technique. In addition to improving the intra-articular congruity, associated ligament and chondral injuries can be detected and treated. This article outlines various associated injuries with suggested management in a stepwise fashion. It is hoped that overall outcomes will be improved once patient-related and treatment-related factors have been evaluated and previously undetected associated ligament injuries have been found and treated. PMID- 28991578 TI - Arthroscopic-Assisted Reduction of Intra-articular Distal Radius Fracture. AB - Wrist arthroscopy is an efficient adjunct for intra-articular distal radius fracture fixation. However, performing wrist arthroscopy during the plate fixation is troublesome with the vertical traction applied and released. To facilitate the procedure, the authors developed a surgical technique, plate presetting arthroscopic reduction technique (PART), using a palmar locking plate. Since July 2005, they have performed PART for 248 intra-articular distal radius fractures with good and excellent results. Arthroscopic-assisted reduction of intra-articular fragments is superior to fluoroscopic assisted. PART also allows detection of intra-articular migration of fracture fragments, screw protrusion, and associated soft tissue injuries. PMID- 28991579 TI - Arthroscopic Management of Intra-articular Malunion in Fractures of the Distal Radius. AB - Treatment of intra-articular malunion of the distal radius has evolved over the past 20 years, from open treatment to wet then dry arthroscopic techniques that provide excellent results with less morbidity than open approaches. Dry wrist arthroscopy provides a well-visualized surgical space in treating intra-articular malunion and results in less edema than wet techniques. The best results are attained in the first 3 months after injury. Alternative methods for avoiding total wrist arthrodesis in those who present later have been developed. The dry arthroscopic "inside-out" osteotomy technique for intra-articular malunions should be considered in patients with this condition. PMID- 28991580 TI - Scaphoid Union: The Role of Wrist Arthroscopy. AB - There are times when clinical examinations, radiographs, and computed tomography scans do not provide sufficient information to know whether a scaphoid fracture or scaphoid bone graft has united, partially united, or not united. When this problem arises, arthroscopic examination of the scaphoid fracture or scaphoid bone graft provides additional information to solve the problem and plan further management in an evidence-based manner. The indications for the use of arthroscopy and surgical technique are described. PMID- 28991581 TI - Arthroscopic Scapholunate Ligament Reconstruction, Volar and Dorsal Reconstruction. AB - Arthroscopic scapholunate volar and dorsal ligament reconstruction achieves an anatomic reconstruction, avoids an open approach and capsular detachment, and provides a strong construct for early mobilization. Clinical results are discussed. Detailed "surgical tips" and technical modifications are provided. PMID- 28991582 TI - Arthroscopic Management of Perilunate Injuries. AB - The key to successful treatment of perilunate injuries is to achieve early anatomic reduction and maintain the carpal alignment. Open surgery may lead to capsular scarring and joint stiffness. Furthermore, there is increased chance of damage of the already tenuous blood supply to scaphoid and the torn ligaments. Recently, arthroscopic-assisted management of perilunate injuries has been suggested. This article describes the surgical technique and outcome of this minimally invasive approach for perilunate injuries. PMID- 28991583 TI - Midcarpal Instability: The Role of Wrist Arthroscopy. AB - The evidence behind management options for midcarpal instability (MCI) is scarce, relying solely on case series. Established treatments cause significant loss of wrist motion. As understanding of the condition has progressed, surgeons have been trying soft tissue techniques. The treatment option should be chosen for the appropriate type and grade of MCI. The Hargreaves grading system for palmar MCI aids treatment decision-making. A possible role for arthroscopy in treatment of MCI has been developed using arthroscopic thermal capsular shrinkage, appropriate for cases with dynamic instabilities. Static deformities require a soft tissue reconstruction or a partial wrist fusion. PMID- 28991584 TI - The Role of Wrist Arthroscopy in Kienbock Disease. AB - Kienbock disease (KD) is a disease of uncertain etiology, leading to chondral and osseous change in the lunate and wrist. Traditionally, Lichtman's classification of KD, based on radiographic appearances, has been used to direct treatment. Diagnostic wrist arthroscopy allows direct assessment of the lunate and surrounding articulations. Wrist arthroscopy can also serve as a therapeutic tool for performing debridement, resection, or arthrodesis procedures. The new Lichtman-Bain algorithm takes into consideration the status of the lunate, the effect on the wrist, and surgical and patient factors to guide management. PMID- 28991585 TI - Arthroscopic-Assisted Partial Wrist Arthrodesis. AB - Partial wrist arthrodesis (PWA) is a well-known procedure for treating degenerative or posttraumatic wrist conditions. Four-corner fusion (4CF) is mostly used for scapholunate advanced collapse and scaphoid nonunion advanced collapse. The author performed 39 procedures, including 4CFs, 2-corner fusions, 3 corner fusions, scaphoid-capitate/scaphoid-capitate-lunate fusions, scaphoid trapezium-trapezoid arthrodeses, and radioscapholunate arthroscopic PWAs (A PWAs). There were 8 revision cases including 4 partial nonunions. All A-PWAs healed satisfactorily after revision surgery. This article discusses the surgical techniques and tips to avoid mistakes. The pros and cons for open versus arthroscopic techniques and for screws versus Kirschner wires are also discussed. PMID- 28991586 TI - Arthroscopic Transplantation of Osteochondral Autograft for Treatment of Cartilage Defects in the Wrist. AB - Focal chondral lesions are a common cause of chronic wrist pain, with no ideal treatment. The authors developed arthroscopic transplantation of osteochondral autograft from lateral femoral condyle to distal radius with satisfactory outcome in 4 consecutive patients between December 2006 and December 2010. In all cases, graft incorporation was completed by 3 months to 4 months postoperation. All patients showed improvement in wrist function with no pain at follow-up at an average of 70.5 months (range 24-116 months). Second-look arthroscopy in 3 patients confirmed the preservation of normal articular cartilage. Patient satisfaction was high with no complications. PMID- 28991587 TI - Arthroscopic Management of Dorsal and Volar Wrist Ganglion. AB - Dorsal and volar wrist ganglions are benign tumors; most of them are asymptomatic. They can disappear spontaneously. Arthroscopic resection can be performed for pain or cosmetic concern. Dorsal ganglion is more common (70%). The hypothesis of the origin is the result of mucoid dysplasia in association with intracapsular and extrasynovial ganglia that occur at the level of the dorsal scapholunate complex. Volar wrist ganglia are less common (20%) and occur mainly in the radiocarpal joint. They are due to capsular destruction at the volar insertion of the SL ligament and arise from the interval between radio scaphocapitate and long radiolunate ligament. PMID- 28991588 TI - Arthroscopic Synovectomy of Wrist in Rheumatoid Arthritis. AB - Rheumatoid arthritis (RA) is a systemic inflammatory disorder affecting multiple joints. Wrist involvement is common. Patients with persistent symptoms despite medical management are candidates for surgery. Synovectomy can provide pain relief and functional improvement for rheumatoid wrist. Arthroscopic synovectomy is a safe and reliable method, with minimal postoperative morbidity. This article reviews the role, technique, and results of arthroscopic synovectomy in the rheumatoid wrist. PMID- 28991589 TI - Arthroscopic Management of Bennett Fracture. AB - Bennett fracture is the most common fracture of the thumb. Choosing the appropriate approach to fracture fixation requires a thorough knowledge of the anatomy surrounding the first carpometacarpal joint, which is necessary to prevent injury to local sensory nerves and tendons. Although no study has shown superior outcomes compared with open reduction internal fixation and fluoroscopically guided closed reduction and percutaneous pinning, arthroscopic assisted fixation allows for debridement of the carpometacarpal joint, direct visualization of the articular surface during reduction, and has minimal morbidity and associated complications. PMID- 28991590 TI - Arthroscopic Management of Thumb Carpometacarpal Joint Arthritis. AB - The thumb carpometacarpal joint (CMCJ1) is born to have good freedom of motion. However, the excellent mobility at this joint also predisposes attenuation of capsuloligamentous structures, joint incongruity, instability, and osteoarthritis. The prevalence of radiographic CMCJ1 arthritis is high. There is no single ideal surgery for all stages of CMCJ1 arthritis, and for all kinds of patients. The arthroscopic approach seems to provide a better alternative with rewarding preliminary results. It includes arthroscopic synovectomy/debridement/thermal shrinkage, arthroscopic partial trapeziectomy and suture button suspensionplasty, and arthroscopic CMCJ1 excision/suture button suspensionplasty/K-wire fixation. PMID- 28991591 TI - Arthroscopic Management of Scaphoid-Trapezium-Trapezoid Joint Arthritis. AB - Scaphoid-trapezium-trapezoid (STT) joint arthritis is a common condition consisting of pain on the radial side of the wrist and base of the thumb, swelling, and tenderness over the STT joint. Common symptoms are loss of grip strength and thumb function. There are several treatments, from symptomatic conservative treatment to surgical solutions, such as arthrodesis, arthroplasties, and prosthesis implant. The role of arthroscopy has grown and is probably the best treatment of this condition. Advantages of arthroscopic management of STT arthritis are faster recovery, better view of the joint during surgery, and possibility of creating less damage to the capsular and ligamentous structures. PMID- 28991592 TI - Progress and Role of Finger Joint Arthroscopy. AB - This article describes the authors' experience with, and recent advancement in, the techniques that have allowed the development of many new arthroscopic procedures in the finger joints. It also describes the role and techniques of arthroscopy in small finger joints. Because the intra-articular anatomy of the first to the fifth metacarpophalangeal (MCP) joints is similar, this article discusses the hand MCP joints without distinguishing thumb from fingers. PMID- 28991593 TI - Complications of Wrist and Hand Arthroscopy. AB - Arthroscopy of the wrist continues to evolve and advance as a valuable clinical technique in hand surgery. This article aims to address safety of wrist arthroscopy and provide an overview of the known iatrogenic complications. Ultimately, the likelihood of associated injuries during wrist arthroscopy is dependent on the surgeon's ability and understanding of the equipment. Case volume and duration of experience directly correlate with mitigating iatrogenic injury and optimizing patient outcomes. PMID- 28991594 TI - Evolution and Inspiration from Hand and Wrist Arthroscopy. PMID- 28991595 TI - Psychometric Properties of the Korean Version of the Infertility Self-Efficacy Scale. AB - PURPOSE: The Infertility Self-Efficacy scale (ISE) is an instrument used to identify infertility-related self-efficacy. The purpose of this study was to assess the reliability and validity of the Korean version of the ISE developed by Cousineau et al. in 2006. METHODS: The translated instrument was pilot-tested and administered to 314 women and men with a diagnosis of infertility. For estimating reliability, test-retest and the internal consistency reliability coefficients were calculated. Validity was evaluated through content validity, concurrent validity, and construct validity with exploratory and confirmatory factor analyses. RESULTS: The internal consistency reliability was satisfactory (Cronbach's alpha = .92, item-total correlations = .44-.80), and the intra-class correlation coefficient was .84 (p < .001). The overall content validity index was 98.1%, and the concurrent validity coefficient (correlations between the ISE scale and general self-efficacy scale) was .31 (p < .001). The final model's fit indexes were acceptable (CFI = .96, NFI = .93, RMSEA = .07, GFI = .94, and SRMR = .03), indicating good construct validity. CONCLUSION: The Korean version of the ISE has high reliability (stability and homogeneity), and good content, concurrent, and construct validity (EFA and CFA). Validated Korean version of the ISE may help nurses identify infertility-related self-efficacy. PMID- 28991596 TI - Community Capacity Building Exercise Maintenance Program for Frail Elderly Women. AB - PURPOSE: The purpose of this study was to examine the effects of community capacity building exercise maintenance program for frail elderly women. METHODS: A quasiexperimental pretest-posttest design was used with nonequivalent control group. The experimental group (n = 22) received community capacity building exercise maintenance program, whereas the control group (n = 23) received health physical exercise program for 16 sessions over 8 weeks. The data of physical fitness, body compositions, self-efficacy, and health-related quality of life were collected three times for both group: before the intervention, immediately after the intervention, and 8 weeks after the intervention. Analyses were conducted using chi2 test, t test, Fisher's exact test, and repeated measures analysis of variance. RESULTS: Compared to the control group, muscular strength (p = .002), static balance (p = .013), muscular endurance (p = .003), self efficacy (p < .001), and health-related quality of life (p = .030) were significantly improved in the experimental group. In addition, body fat percentage (p = .005) in this group was significantly decreased after the community capacity building exercise maintenance program. CONCLUSION: Theses results indicated that a community capacity building exercise maintenance program is feasible, and associated with exercise maintenance among frail elderly women. PMID- 28991597 TI - Protective Factors of Demoralization among Cancer Patients in Taiwan: An Age matched and Gender-matched Study. AB - PURPOSE: This study aimed to explore the protective factors of demoralization in cancer patients via investigation of cancer patients' demographic and disease characteristics. METHODS: This was a cross-sectional descriptive study. We used a structured questionnaire, which contained items on demographic and disease characteristics, as well as the Demoralization Scale Mandarin Version (DS-MV), with a cutoff of 30 or more indicating high demoralization. Data were analyzed with age-matched and gender-matched conditional logistic regression analysis. For the study, 428 questionnaires were delivered and 411 were recovered. After being age-matched and gender-matched, 182 participants of high demoralization (DS-MV > 30) and low demoralization (DS-MV <= 30) were obtained respectively, for a total of 364 participants. RESULTS: Cancer patients' demoralization was significantly related to family support (p = .019), education (p = .049), and monthly income (p = .001). Family support [odds ratio = 0.38; p = .028; 95% confidence interval (0.16, 0.91)] and monthly income [odds ratio = 0.49; p = .009; 95% confidence interval (0.29, 0.84)] were protective factors of demoralization in cancer patients. CONCLUSION: Early and appropriate demoralization assessment of cancer patients' demographic and disease characteristics is very important in clinical settings. Healthcare providers might regularly monitor demoralization in cancer patients, and develop related nursing care guidelines or treatment for demoralization in cancer patients. The study results can be a reference for healthcare providers who work with cancer patients. PMID- 28991598 TI - Evaluating the Factor Structure of the Persian Version of Posttraumatic Growth Inventory in Cancer Patients. AB - PURPOSE: This study aimed to assess the factor structure of the Persian version of posttraumatic growth inventory (P-PTGI). METHODS: Participants included 272 Iranian people of Azari ethnicity (111 women and 161 men), aged between 21 and 91 years (mean 52.65 years), who were diagnosed with cancer and were referred to the oncology department of the university hospital. The P-PTGI was assessed to determine the construct validity, using various indices of confirmatory factor analysis and standardized lambda coefficient, followed by further assessment of the discriminant and convergent validities by using the structural equation model. LISREL 8.8 for Windows and SPSS were used for data analysis. RESULTS: The calculated values of comparative fit index, incremental fit index, normed fit index, and non-normed fit index > .90 and the values of standardized root-mean square residual < .08 indicate an acceptable fit for the original PTGI. Considering that the values of average variance extracted (.52-.74) were greater than the square of correlation coefficients between the five dimensions of P PTGI, discriminant validity was approved. Convergent validity was confirmed through a high value of standardized lambda coefficient (.52-.92) between the items and their related factors. CONCLUSIONS: This study revealed that P-PTGI has an acceptable validity and reliability for posttraumatic growth assessment in Iranian cancer patients and its factor structure is similar to that of the original form developed by Tedeschi and Calhoun. PMID- 28991599 TI - Examination of a Nurse-led Community-based Education and Coaching Intervention for Coronary Heart Disease High-risk Individuals in China. AB - PURPOSE: Early detection and management of coronary heart disease (CHD) are embedded into many community health service and primary care practices in western countries. The Framingham CHD risk score has been used to predict CHD and mortality for nearly 20 years, and it has predicted CHD event risk accurately in multiethnic populations. The aim of this study was to access the effect of a 6 month community-based intervention on CHD risk in individuals at high risk. METHODS: A randomized controlled trial of individuals with a high 10-year CHD risk were recruited from two communities in China. Individuals in the intervention group (n = 53) received a 3-month group education and a 3-month coaching session. Physical examination and self-report questionnaires were used to collect both pre- and postintervention data on blood pressure, glucose, cholesterol, body mass index, smoking, depression, and health-related quality of life (HRQoL). RESULTS: A total of 102 participants (85.0%) completed the 6-month study. Compared with the usual care group, the intervention group had a 5 mmHg greater reduction in systolic blood pressure (t = 2.01, p = .047), larger declines in glucose (t = -2.49, p = .015), cholesterol (t = -2.44, p = .017), body mass index (t = -2.58, p = .011), and depression (t = -2.05, p = .043), and better reports of HRQoL (t = 3.36, p = .001). No significant group differences in smoking behaviors were reported. CONCLUSION: A 6-month community-based intervention in a CHD high-risk population improved disease-related risk factors, depression, and HRQoL. Results provide preliminary evidence for primary prevention of cardiovascular disease risk in a community high-risk population. PMID- 28991600 TI - The Effects of Reflective Training on the Disposition of Critical Thinking for Nursing Students in China: A Controlled Trial. AB - PURPOSE: The aim of this study was to evaluate the effects of reflective trainings for nursing students on their critical thinking disposition. METHODS: A total of 157 senior undergraduate nursing students sampled from Hainan Medical University in China participated in this study in 2014. They were randomly divided into experimental and control groups. The experimental group students were provided the reflective training during their entire 12-month clinical internship, whereas students in the control group were requested to keep their reflective diaries but without a formal training. Before and after the intervention, nursing students' critical thinking disposition was rated using the Chinese version of Critical Thinking Disposition Inventory (CTDI-CV). RESULTS: Before the start of the intervention, the critical thinking disposition scores of the two groups had no significant differences. At the end of the intervention, it was found that the experimental students performed better in each subscale of CTDI-CV. These include the search for truth, open mind, analytical ability, systematic ability, critical thinking, self-confidence, curiosity, and cognitive maturity. By summing the scores of all categories, the results showed that the experimental group had a significantly higher total score than that of the control group (p <= .044). Evaluating the score difference in each function indicated that there was a range of improvements on the critical thinking disposition because of the reflective training intervention. CONCLUSION: Reflective training during the internship period improves nursing students' disposition of critical thinking and promotes their readiness for their clinical practices in the rapidly increasing demands of the healthcare field. PMID- 28991601 TI - Confrontation as a Mediator between Sense of Coherence and Self-management Behaviors among Elderly Patients with Coronary Heart Disease in North China. AB - PURPOSE: Self-management is critical to improve health outcomes of elderly patients with coronary heart disease (CHD). Sense of coherence (SOC) is found to be linked with self-management behaviors. However, their deeper relationship is not clear. The purposes of this study were to investigate the association between SOC and self-management behaviors among elderly CHD patients in China, and whether confrontation mediates this association. METHODS: A cross-sectional design was used. A total of 275 elderly patients with CHD recruited from the cardiology department in a general hospital in North China were surveyed from October 2015 to April 2016. SOC, confrontation, and self-management behaviors were measured using the Chinese version of the SOC scale, subscale of Medical Coping Modes Questionnaire-Confrontation, and the CHD self-management scale, respectively. Correlation analysis and path analysis were conducted to analyze the data. RESULTS: The mean (+/-standard deviation) scores of SOC, confrontation, and self-management behaviors were 62.20 (+/-9.61), 19.55 (+/-3.15), and 76.17 (+/-10.63), respectively. Correlation analysis showed that SOC, confrontation, and self-management behaviors were significantly correlated with each other. Path analysis indicated that SOC exerted a direct effect on self-management behaviors, whereas could affect self-management indirectly via confrontation. Bootstrap test result showed that confrontation played a mediating role (beta = .20, p < .001) in the relationship between SOC and self-management behaviors. CONCLUSION: SOC was related to self-management behaviors, whereas confrontation mediated the effect of SOC on self-management behaviors. In practice, the role of confrontation coping should be valued when developing strategies to strengthen SOC and to improve self-management practice among elderly CHD patients. PMID- 28991602 TI - Nurses' Experiences of End-of-life Care in Long-term Care Hospitals in Japan: Balancing Improving the Quality of Life and Sustaining the Lives of Patients Dying at Hospitals. AB - PURPOSE: In Japan, about 80% of deaths occur in hospitals, especially long-term care beds. The purpose of this study was to clarify the nursing practices used for such older patients at the end-of-life stage in long-termcare wards via the modified grounded theory approach (M-GTA). METHODS: Data were obtained through semi-structured interviews of nineteen nurses working in cooperating long-term care wards, acute care wards, or hospice services (to allow for constant comparison between these types of wards) in western Japan in 2014. We analyzed the transcribed data using M-GTA. RESULTS: The core category that emerged from the analysis was "Balancing enhancement of patients' daily life quality and life sustaining care in the face of uncertainty about the patients' character." Eleven categories emerged, such as Seeking older patients' character with their family, Supporting families' decision making, Rebuilding patients' daily life in the ward, and Sustaining patients' life span through medical care. CONCLUSIONS: Nurses experienced uncertainty about the care needs of older patients, the ethical problems of Enhancing the patients' QOL by using risky care, and the evaluation criteria used to judge their own nursing care after the patients' death. All nurses had the goal of ensuring a natural death for all patients. Nurses' acceptance and evaluation of their own care was critically influenced by the patient's family's responses to their care after patients' death. Further research is necessary to develop evaluation criteria and educational programs for end-of-life nursing care of older adults. PMID- 28991603 TI - Nurses' Opinions of Patient Involvement in Relation to Patient-centered Care During Bedside Handovers. AB - PURPOSE: Advocates for societal change and consumerism have been instrumental in popularizing patient involvement in various aspects of health care. Patient involvement in bedside handovers during shift changes should facilitate patient centered care. This study's purpose was to explore Malaysian nurses' opinions about patient involvement during bedside handovers, and whether patient involvement during bedside handovers reflected patient-centered care. METHODS: A qualitative study with four focus-group discussions was conducted with 20 registered nurses from general wards in a Malaysian public hospital. Semi structured interviews were used to elicit participants' opinions. NVivo 10 software was used for data management and content analysis was used to analyze the data. RESULTS: Several participants used inconsistent methods to involve patients in bedside handovers and others did not involve the patients at all. The participants' interpretations of the concept of patient-centered care were ambiguous; they claimed that patient involvement during bedside handovers was impractical and, therefore, not reflective of patient-centered care. Some nurses' subjective views of patient involvement as impractical during bedside handovers were manifested in their deliberate exclusion of patients from the handover process. CONCLUSIONS: Changes in patient involvement and nursing practices congruent with patient-centered care require that nurse educators in hospital settings reform nursing education to focus on fostering of communication skills needed to function in nurse-patient partnerships. Guidelines for patient involvement consistent with patient-centered values should be developed using ward nurses' subjective views and introduced to all registered nurses in practice. PMID- 28991604 TI - Comparisons of Cardiometabolic Biomarkers, Lifestyle Behaviors, and Dietary Sodium and Potassium Intake in a Representative Sample of Korean Adults with and without Cardio-cerebrovascular Diseases. AB - PURPOSE: To compare the cardiometabolic condition of obesity, blood pressure (BP), cholesterol, dietary sodium and potassium intake, and lifestyle behaviors of persons with cardio-cerebrovascular diseases, with those who are disease-free in Korea. METHODS: A secondary data analysis was conducted using a representative sample of Korean adults. RESULTS: Of 10,906 Korean adults (mean age 43.12 +/- 0.24 years, women 50.4%), 9,074 were disease-free and 1,520 had hypertension, 137 stroke, and 175 ischemic heart disease. Compared with the disease-free group, obesity, BP, and total cholesterol were higher for the hypertensives. 25.5% of ischemic heart disease group were still smoking; 14.9% of hypertensives were heavy alcohol drinkers. Physical activity was lower in cardio-cerebrovascular diseases than disease-free group. No significant association was found between Na/K ratio adequacy and types of cardio-cerebrovascular diseases. CONCLUSION: The cardiometabolic condition varied, with hypertensives having a higher prevalence for obesity, high BP, and cholesterol; poorer adherence to the behavioral recommendations was also noted in cardio-cerebrovascular diseases. Such variations in cardiovascular risks would provide implications for addressing vulnerability across groups. PMID- 28991606 TI - Zombie issues in ophthalmology. PMID- 28991605 TI - Exploring Nursing Intention, Stress, and Professionalism in Response to Infectious Disease Emergencies: The Experience of Local Public Hospital Nurses During the 2015 MERS Outbreak in South Korea. AB - PURPOSE: This study aimed to examine levels of stress and professionalism of nurses who provided nursing care during the 2015 Middle East respiratory syndrome outbreak based on their experience, to investigate the nurses' intention to respond to possible future outbreaks in relation to their experience during the outbreak, and to determine the relationship between the outbreak experience and nursing intention considering stress and professionalism. METHODS: A self administered questionnaire was designed based on modifications of related questionnaires, and used to assess levels of stress, professionalism, and nursing intention according to participants' experiences during the outbreak. Multiple regression analysis was used to examine the relationship between the outbreak nursing experience and nursing intention considering stress and nursing professionalism. RESULTS: The overall stress, professionalism, and nursing intention scores for the firsthand experience group were 33.72, 103.00, and 16.92, respectively, whereas those of the secondhand experience group were 32.25, 98.99, and 15.60, respectively. There were significant differences in professionalism and nursing intention scores between the groups (p = .001 and p < .001, respectively). The regression analysis revealed that the regression estimate between stress and nursing intention was B(SE) = -0.08(0.02), beta = 0.21, p < .001 and the regression estimate between professionalism in nursing and nursing intention was B(SE) = 0.05(0.01), beta = 0.23, p < .001. CONCLUSION: Prior outbreak nursing experience was importantly associated with intention to provide care for patients with a newly emerging infectious disease in the future considering stress and professionalism. Gathering information about nurses' experience of epidemics and regular assessment of job stress and professionalism are required. PMID- 28991607 TI - Long-term effects of cataract surgery with topical levofloxacin on ocular bacterial flora. AB - PURPOSE: To clarify the long-term effect of topical antibiotics on the ocular bacterial flora after cataract surgery. SETTING: Miyata Eye Hospital, Miyazaki, Japan. DESIGN: Prospective case series. METHODS: Patients who had cataract surgery between November 2014 and January 2015 were included. Levofloxacin 1.5% was administered 4 times a day by topical instillation from 3 days before surgery to 1 month postoperatively. The conjunctival sacs of patients were scraped before the procedure and 0, 3, 6, 9, and 12 months after the last instillation. The samples were cultured, and minimum inhibitory concentrations (MICs) of levofloxacin for Staphylococcus epidermidis and Propionibacterium acnes were evaluated using mixed-effects models. RESULTS: The study evaluated 50 patients. Diverse bacterial species, predominantly S epidermidis and P acnes, were isolated before the application of topical levofloxacin. Bacterial diversity was substantially reduced after the final topical levofloxacin application and subsequently increased after 3 months. However, the geometric mean levofloxacin MICs for S epidermidis isolates were still significantly higher at 0 months and 3 months than before treatment (P < .01 and P = .03, respectively) and reached pretreatment levels 6 months and 12 months after the last application. Propionibacterium acnes did not show significant changes in the geometric mean levofloxacin MIC over time. CONCLUSION: The restoration of the bacterial flora required more than 6 months after cataract surgery and topical levofloxacin. PMID- 28991608 TI - Effect of high-vacuum setting on phacoemulsification efficiency. AB - PURPOSE: To evaluate the effect of a high-vacuum setting versus a low-vacuum setting on the efficiency of phacoemulsification. SETTING: Sunderland Eye Infirmary, Sunderland, United Kingdom. DESIGN: Prospective clinical trial. METHODS: Consecutive patients having cataract surgery in 2014 were recruited. Cataract surgery was performed by 2 experienced surgeons using a phacoemulsification machine with monitored forced infusion. The cataractous lens was split into 2 heminuclei using the stop-and-chop technique; in 1 heminucleus, phacoemulsification and aspiration used a high-vacuum setting (600 mm Hg; treatment group) and in the other heminucleus, a low-vacuum setting (350 mm Hg; control group). The high and low settings were alternated by case per the operating list to reduce surgeon bias. The main outcome measures were cumulative dissipated energy (CDE) and active heminucleus removal time. RESULTS: One hundred sixty patients (160 eyes) were enrolled in the study, and 158 were included in the analysis. The CDE per heminucleus was significantly lower with the high vacuum setting than with the low-vacuum setting (mean 2.81 percent-seconds; 95% confidence interval (CI), 2.44-3.21 versus 3.81 percent-seconds; 95% CI, 3.38 4.20; P < .001). The active heminucleus removal time was significantly shorter in the high-vacuum group than the low-vacuum group (mean 27.77 seconds; 95% CI, 25.26-30.19 versus 33.59 seconds; 95% CI, 31.07-35.92; P < .001). The observed differences were independent of the surgeon, patient age and sex, incision size, and nucleus density. No intraoperative complications were observed in either group. CONCLUSION: A high-vacuum setting improved phacoemulsification efficiency using an active fluidics system and torsional phacoemulsification. PMID- 28991609 TI - Optimized keratometry and total corneal astigmatism for toric intraocular lens calculation. AB - PURPOSE: To compare keratometric astigmatism (KA) and different modalities of measuring total corneal astigmatism (TCA) for toric intraocular lens (IOL) calculation and optimize corneal measurements to eliminate the residual refractive astigmatism. SETTING: G.B. Bietti Foundation IRCCS, Rome, Italy. DESIGN: Prospective case series. METHODS: Patients who had a toric IOL were enrolled. Preoperatively, a Scheimpflug camera (Pentacam HR) was used to measure TCA through ray tracing. Different combinations of measurements at a 3.0 mm diameter, centered on the pupil or the corneal vertex and performed along a ring or within it, were compared. Keratometric astigmatism was measured using the same Scheimpflug camera and a corneal topographer (Keratron). Astigmatism was analyzed with Naeser's polar value method. The optimized preoperative corneal astigmatism was back-calculated from the postoperative refractive astigmatism. RESULTS: The study comprised 62 patients (64 eyes). With both devices, KA produced an overcorrection of with-the-rule (WTR) astigmatism by 0.6 diopter (D) and an undercorrection of against-the-rule (ATR) astigmatism by 0.3 D. The lowest meridional error in refractive astigmatism was achieved by the TCA pupil/zone measurement in WTR eyes (0.27 D overcorrection) and the TCA apex/zone measurement in ATR eyes (0.07 D undercorrection). In the whole sample, no measurement allowed more than 43.75% of eyes to yield an absolute error in astigmatism magnitude lower than 0.5 D. Optimized astigmatism values increased the percentage of eyes with this error up to 57.81%, with no difference compared with the Barrett calculator and the Abulafia-Koch calculator. CONCLUSION: Compared with KA, TCA improved calculations for toric IOLs; however, optimization of corneal astigmatism measurements led to more accurate results. PMID- 28991610 TI - Intraocular lens power calculation for eyes with high and low average keratometry readings: Comparison between various formulas. AB - PURPOSE: To compare the accuracy of intraocular lens power prediction for eyes with average keratometry (K) readings greater than 46.00 diopters (D) and lower than 42.00 D. SETTING: Ein-Tal Eye Center, Tel-Aviv, Israel. DESIGN: Retrospective case series. METHODS: Eyes having cataract extraction surgery with steep and flat preoperative corneal curvatures determined with the Lenstar-LS900 device were enrolled. Refractive prediction errors for the Barrett Universal II, Haigis, Hill-RBF, Hoffer-Q, Holladay 1, Holladay 2, Olsen, and SRK/T formulas were compared. Optimized K values for the SRK/T formula were back-calculated for each group. Validation was performed using an additional dataset. RESULTS: The study comprised 171 eyes (79, K reading >46.00 D; 92, K reading <42.00 D). For K readings greater than 46.00 D, myopic errors were noted using the SRK/T and Hill RBF formulas and hyperopic errors using the Olsen C-constant and Haigis (-0.31 D, -0.17 D, 0.18 D, and 0.17 D, respectively). The percentage of eyes with an absolute error within +/-0.50 D from target refraction ranged from 60.8% (SRK/T) to 83.0% (Hill-RBF). For K readings lower than 42.00 D, myopic errors were seen using the Haigis, Hill-RBF, Hoffer-Q, and Olsen-C formulas (-0.31 D, -0.14 D, 0.22 D, and -0.17 D, respectively) and a hyperopic error using the SRK/T formula (0.16 D). The refractive prediction within +/-0.50 D ranged between 75.0% (Haigis) and 96.7% (Barrett Universal II). CONCLUSIONS: Power calculation for eyes with flat corneas and steep corneas requires the use of specific formulas for accurate postoperative results. An adjustment method of the SRK/T formula is proposed. PMID- 28991611 TI - Effect of fixation stability during biometry measurements on refractive prediction accuracy in highly myopic eyes. AB - PURPOSE: To assess the effect of preoperative biometry fixation stability on postoperative refractive errors in highly myopic cataractous eyes. SETTING: Eye and ENT Hospital of Fudan University, Shanghai, China. DESIGN: Prospective cohort study. METHODS: Eyes of highly myopic patients and emmetropic controls were included. Routine ophthalmologic examinations and measurement of fixation stability in the 63% and 95% bivariate contour ellipse areas (BCEAs) were conducted preoperatively. The refractive error from prediction was calculated 1 month postoperatively with the SRK/T and Holladay 1 formulas. Univariate and multivariable analyses were performed to identify the factors associated with postoperative refractive errors. RESULTS: The refractive errors were more widely distributed in the 45 highly myopic eyes than in the 40 emmetropic control eyes: SRK/T, +0.15 diopter [D] +/- 0.80 [SD] and -0.16 +/- 0.35 D, respectively; Holladay 1, +0.54 +/- 0.79 D and -0.23 +/- 0.34 D, respectively. In the highly myopic group, 63% BCEA was correlated with axial length (AL) (P = .021) and posterior subcapsular opacity grade (P = .040). With both formulas, refractive errors and absolute refractive errors were positively correlated with 63% BCEA: SRK/T, P = .010 and P = .001, respectively; Holladay 1, P = .006 and P = .003, respectively. Backward multiple linear regression analysis showed that with both formulas, AL and 63% BCEA were significantly associated with postoperative refractive errors. CONCLUSION: Poor preoperative biometry fixation stability correlated with long AL and severe posterior subcapsular opacity contributed to significant deviation of refractive errors after cataract surgery in highly myopic eyes. PMID- 28991613 TI - Safety of femtosecond laser-assisted primary posterior capsulotomy immediately after cataract surgery. AB - PURPOSE: To evaluate the safety and feasibility of a new femtosecond laser assisted method for posterior capsule opacification (PCO) prevention. SETTING: University Eye Hospital Bochum, Bochum, Germany. DESIGN: Prospective randomized intraindividual case series. METHODS: Eyes scheduled for bilateral cataract surgery between April 2015 and January 2016 were enrolled in the study. In 1 eye, routine manual cataract surgery with intraocular lens (IOL) implantation was performed with a primary posterior laser capsulotomy as the last step in the procedure. For the laser treatment, the posterior capsule between the anterior hyaloid surface and the posterior optic surface of the IOL was identified with integrated 3-dimensional spectral-domain optical coherence tomography. In the fellow eye, routine manual cataract surgery without posterior capsulotomy was performed. Follow-up examinations were done 1 week, 2 months, and 6 months after surgery. The main outcome measures were feasibility of the procedure and between group difference in visual acuity, macular thickness, laser flare, intraocular pressure (IOP), and PCO. RESULTS: Fifty-six eyes were included. No differences in cataract density (P = .2), axial length (P = .8), or amount of ultrasound energy used (P = .55) were found between the groups. In all cases, it was possible to identify and target the posterior capsule. In 1 case, a minimal attachment of a half-hour length was seen. No significant between-group differences in visual acuity, macular thickness, laser flare, or IOP were seen. CONCLUSION: The described off-label use of primary posterior laser capsulotomy was a safe, feasible technique in preventing PCO over a 6-month follow-up. PMID- 28991614 TI - Postoperative outcomes of intraocular lens implantation in the bag versus posterior optic capture in pediatric cataract surgery. AB - PURPOSE: To compare complications in children up to 4 years old having cataract surgery with intraocular lens (IOL) implantation using 2 techniques: in-the-bag IOL with anterior vitrectomy or optic capture of IOL with no anterior vitrectomy. SETTING: Iladevi Cataract & IOL Research Centre, Ahmedabad, India. DESIGN: Prospective randomized control clinical trial. METHODS: The study included children having cataract surgery with IOL implantation. Patients were randomized to Group 1 (in-the-bag 3-piece hydrophobic acrylic IOL [Acrysof MA60AC] with anterior vitrectomy) or Group 2 (optic capture of the same IOL without anterior vitrectomy). Intraoperative complications were documented. Postoperative visual axis obscuration (VAO), glaucoma, cell deposits on the IOL, and posterior synechiae were compared at 1, 3, 6, and 12 months. RESULTS: The study comprised 61 children (61 eyes). The mean ages were 14.8 months +/-11.47 (SD) in Group 1 (n = 30) and 18.2 +/- 11.47 months in Group 2 (n = 31). Overall, only 1 eye in Group 1 developed a VAO requiring membranectomy 4 months postoperatively, and 2 eyes in Group 1 developed glaucoma over 12 months (P = .49). Intraocular lens cell deposits and posterior synechiae were comparable between groups. The IOL could not be captured in 5 eyes (16.1%); no complications occurred in these eyes. CONCLUSIONS: Optic capture of 3-piece hydrophobic acrylic IOLs could be achieved in most eyes. The VAO, glaucoma, and inflammation were comparable 12 months postoperatively. Thus, optic capture of an IOL is an alternative surgical technique that can be used to avoid vitrectomy, even in children younger than 4 years. PMID- 28991612 TI - Long-term safety follow-up of an anterior chamber angle-supported phakic intraocular lens. AB - PURPOSE: To report adverse device effects and annualized endothelial cell loss rate for up to 10 years after implantation of the Acrysof L-series Cachet phakic intraocular lens (pIOL). SETTING: Clinical centers in the United States, European Union, and Canada. DESIGN: Nonrandomized clinical trial. METHODS: After implantation of the pIOL, the endothelial cell density (ECD) at follow-up evaluations was compared with the 6-month postoperative baseline. Adverse device effects were assessed. RESULTS: This study assessed 638 patients (1087 eyes) from previous clinical trials. The mean central ECD change from baseline was -9.6% +/- 8.3% (SD) (-1.7% annualized; 623 eyes) and -11.0% +/- 9.9% (-1.7% annualized; 703 eyes) at 6 years and 7 years, respectively. The mean peripheral ECD change from baseline was -10.8% +/- 8.7% (-2.0% annualized; 615 eyes) and -11.9% +/- 10.0% ( 1.8% annualized; 680 eyes), respectively. Endothelial cell loss greater than 30% from the preoperative baseline at any time after implantation affected 8.0% of all eyes. An ECD of 1500 cells/mm2 or less at any time after implantation affected 2.7% of all eyes. The most common adverse device effects were peripheral iris adhesions (57 eyes [5.2%]), corneal endothelial cell loss (42 eyes [3.9%]), and pIOL explantation (37 eyes [3.4%]). CONCLUSIONS: Long-term evaluation of the pIOL showed a persistent ECD decrease in some eyes that was numerically larger than the annual rate expected with aging. Endothelial cell loss resulted in explantation in 3.1% of all eyes with the pIOL. Patients had no permanent vision loss. The manufacturer recommends that patients continue to be monitored and their corneal endothelium evaluated semiannually. PMID- 28991615 TI - Optimizing number of postoperative visits after cataract surgery: Safety perspective. AB - PURPOSE: To evaluate safety perspectives when the standard routine after cataract surgery is no planned postoperative visit. SETTING: Eye Clinic, Sunderby Hospital, Lulea, Norrbotten County, Sweden. DESIGN: Prospective case series. METHODS: All cataract surgery cases during a 1-year period were included. The study group had the standard routine at the clinic, that is, no planned postoperative visit for patients without comorbidity and uneventful surgery. For the control group, patients who had surgery during 1 month of the 1-year period were chosen. All these patients had a planned postoperative visit. All surgeons involved were experienced. The outcome measures were any planned postoperative visit, any complication and/or adverse event, postoperative corrected distance visual acuity (CDVA), and any postoperative control/contact initiated by the patient. RESULTS: The study comprised 1249 patients (1115 in the study group and 134 in the control group). No significant differences in demographics, postoperative CDVA, frequency of planned visits because of ocular comorbidity, or postoperative patient-initiated contacts were found between the 2 groups. Of the 1249 patients, 9% (117 patients) initiated a postoperative contact, of whom 26% (30 patients) also had a scheduled visit. The reasons for the patient-initiated contacts were visual disturbance, redness and/or chafing, pain, and anxiety. An evaluation of all medical records 2 years postoperatively found no reports of missed adverse events. CONCLUSIONS: It was possible to refrain from planned postoperative visits for patients having uncomplicated cataract surgery. However, preoperatively, patients with comorbidities should be provided with individual planning of their postoperative follow-up. Preoperative counseling is important, and the clinic must have resources to answer questions from patients and be prepared for additional unplanned postoperative visits. PMID- 28991616 TI - Refractive lens exchange and piggyback intraocular lens implantation in nanophthalmos: Visual and structural outcomes. AB - PURPOSE: To evaluate the best piggyback intraocular lens (IOL) implantation method and the outcomes in nanophthalmos eyes and to define the postoperative structural changes. SETTING: Farabi Eye Hospital, Tehran, Iran. DESIGN: Prospective case series. METHODS: Candidates for refractive surgery who were nanophthalmic were recruited. Patients had refractive lens exchange followed by implantation of both IOLs in the bag or 1 IOL in the bag and 1 IOL in the sulcus. The baseline and follow-up visual acuity, refractive status, and structural Scheimpflug imaging were evaluated. Ultrasound biomicroscopy (UBM) was performed 6 months postoperatively. RESULTS: The study comprised 9 nanophthalmic patients (18 eyes) with a mean preoperative uncorrected distance visual acuity (UDVA) of 1.53 logarithm of the minimum angle of resolution (logMAR) +/- 0.3 (SD), mean corrected distance visual acuity (CDVA) of 0.34 +/- 0.2 logMAR, and mean spherical equivalent (SE) of +13.55 +/- 4.0 diopters (D). The mean postoperative UDVA improved from baseline. There was no significant difference in the mean UDVA and CDVA between the 2 IOL groups. Postoperatively, both groups had a significant improvement in SE, a significant rise in anterior chamber depth and angle, and similar UBM measurements. CONCLUSIONS: Piggyback IOL implantation was an effective refractive procedure in nanophthalmic eyes. Both implantation methods resulted in similar outcomes; however, the small number of patients in each group made it less likely that possible differences would be found. The increase in angle values might help prevent the development of closed-angle glaucoma. PMID- 28991617 TI - Goniotomy with a single-use dual blade: Short-term results. AB - PURPOSE: To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of a single-use dual blade (Kahook) in patients with mild to end-stage glaucoma. SETTING: International multicenter ophthalmic care centers. DESIGN: Prospective interventional case series. METHODS: Consecutive patients with glaucoma who had phacoemulsification plus goniotomy with the single-use dual blade were enrolled in this study. Each center collected deidentified clinical data, including preoperative and postoperative IOP, medication use, adverse events, and whether additional surgery was required during a 6-month follow-up. RESULTS: Of the 71 eyes included in this study, 70% had primary open-angle glaucoma. Other diagnoses included angle-closure, pigmentary, pseudoexfoliative, and normal-tension glaucoma. Sixty-five percent of eyes were classified as having mild to moderate glaucoma and 35%, severe glaucoma. The mean baseline IOP decreased from 17.4 mm Hg +/- 5.2 (SD) to 12.8 +/- 2.6 mm Hg 6 months postoperatively and the hypotensive medication use decreased from 1.6 +/- 1.3 to 0.9 +/- 1.0, respectively (P < .001 and P = .005, respectively). The most common observation was blood reflux during surgery (39.4%). CONCLUSION: Single-use dual blade goniotomy plus phacoemulsification resulted in a significant and sustained reduction in IOP and a decrease in glaucoma medications after 6 months of follow up. PMID- 28991618 TI - Optimization of transversal phacoemulsification settings in peristaltic mode using a new transversal ultrasound machine. AB - PURPOSE: To determine the optimum bottle height, vacuum, aspiration rate, and power settings in the peristaltic mode of the Whitestar Signature Pro machine with Ellips FX tip action (transversal). SETTING: John A. Moran Eye Center Laboratories, University of Utah, Salt Lake City, Utah, USA. DESIGN: Experimental study. METHODS: Porcine lens nuclei were hardened with formalin and cut into 2.0 mm cubes. Lens cubes were emulsified using transversal and fragment removal time (efficiency), and fragment bounces off the tip (chatter) were measured to determine optimum aspiration rate, bottle height, vacuum, and power settings in the peristaltic mode. RESULTS: Efficiency increased in a linear fashion with increasing bottle height and vacuum. The most efficient aspiration rate was 50 mL/min, with 60 mL/min statistically similar. Increasing power increased efficiency up to 90% with increased chatter at 100%. CONCLUSION: The most efficient values for the settings tested were bottle height at 100 cm, vacuum at 600 mm Hg, aspiration rate of 50 or 60 mL/min, and power at 90%. PMID- 28991619 TI - Light scattering levels from intraocular lenses extracted from donor eyes. AB - PURPOSE: To assess light scatter levels of intraocular lenses (IOLs) extracted from donor eyes to understand straylight elevation documented earlier in pseudophakic population studies and identify potential sources of light scattering in IOLs. SETTING: Rotterdam Ophthalmic Institute, Rotterdam, the Netherlands. DESIGN: Experimental study. METHODS: Light scattering in 74 donor IOLs was measured with the C-Quant device adapted for in vitro analysis of IOLs. Straylight was assessed at a 2.5-degree and 7.0-degree scatter angle, and results were compared with the straylight of a 20-year-old crystalline lens, a 70-year old crystalline lens, and a lens with cataract. To identify potential changes to the IOL material, the IOLs were examined with a light microscope and a slitlamp. RESULTS: At 2.5 degrees and 7.0 degrees, the straylight parameter was 5.78 deg2/steradian (sr) +/- 4.70 (SD) and 5.06 +/- 4.01 deg2/sr, respectively. Forty one percent of IOLs showed lower straylight than the 20-year-old lens. In 14%, the scattering intensity was higher than in the 70-year-old lens; none showed straylight comparable to that of the cataractous lens. Increased straylight was associated with surface deposits, snowflake-like degeneration, and glistenings. The incidence of IOL-related complications differed between the IOL groups. CONCLUSIONS: Microscopic structural alterations of IOLs play a major role in straylight elevations in pseudophakic eyes. A clear correlation with degeneration and/or alteration of implanted IOLs was found. Although these IOL-related complications would likely not affect visual acuity, they give rise to straylight and thus can cause disability glare and other symptoms. PMID- 28991620 TI - New perspectives on the detection and progression of keratoconus. AB - Laser refractive surgery has increased markedly in recent years, making the detection of corneal abnormalities extremely relevant. For this reason, an accurate diagnosis of clinical or subclinical keratoconus is critical. Corneal topography is the primary diagnostic tool for keratoconus detection, and pachymetry data and corneal aberrations are also commonly used. Recently, tomographic measurements using optical coherence tomography and corneal biomechanical indices have been used. In incipient and subclinical keratoconus, the use of a single parameter as a diagnostic factor is not sufficiently accurate. In these cases, the use of algorithms and predictive models is necessary. In addition, determining whether the disease will progress is crucial to selecting the most appropriate treatment. Some factors, such as age, keratometric indices, corneal elevation data, and corneal thickness, seem to be useful in predicting keratoconus progression. PMID- 28991621 TI - Central island formation after cataract surgery in a laser in situ keratomileusis eye: New etiology. AB - We report a case of central corneal steepness formation after cataract surgery in a post-laser in situ keratomileusis (LASIK) eye. A 51-year-old woman with traumatic cataract and a history of myopic LASIK surgery had uneventful phacoemulsification cataract surgery. Postoperatively, the corneal topography difference map showed a central island formation of 2.1 diopters (D) compared with the preoperative level, which correlated with a clinical myopic shift of 2.00 D from the targeted emmetropia. At 4 months, most of the central island had resolved spontaneously. At 15 months, topography returned to preoperative levels. We speculate that wound hydration in the flap interface during surgery resulted in a pond-like fluid accumulation in the center of the cornea, resulting in a myopic refractive shift. We report this case because of the high probability that this phenomenon could be confounded by an erroneous intraocular lens (IOL) calculation and the potential for a serious iatrogenic complication from a premature IOL exchange or touch-up procedure. PMID- 28991622 TI - Presbyopia correction after previous refractive laser and cataract surgery: September consultation #1. PMID- 28991623 TI - September consultation #2. PMID- 28991624 TI - September consultation #3. PMID- 28991625 TI - September consultation #4. PMID- 28991627 TI - September consultation #7. PMID- 28991626 TI - September consultation #5. PMID- 28991628 TI - September consultation #6. PMID- 28991629 TI - September consultation #8. PMID- 28991630 TI - Editor's Comment. PMID- 28991631 TI - Primary femtosecond laser posterior capsulotomy: Without clinical outcomes, caution should be exercised. PMID- 28991632 TI - Reply. PMID- 28991633 TI - Descemet-stripping endothelial keratoplasty and flange technique of scleral fixation of intraocular lens: Making it easier and safer. PMID- 28991634 TI - Reply. PMID- 28991635 TI - Reply. PMID- 28991637 TI - Erratum. PMID- 28991636 TI - Autologous blood as a sealant for conjunctival autografts. PMID- 28991638 TI - Erratum. PMID- 28991639 TI - Haemanthamine alters sodium butyrate-induced histone acetylation, p21WAF1/Cip1 expression, Chk1 and Chk2 activation and leads to increased growth inhibition and death in A2780 ovarian cancer cells. AB - BACKGROUND: Haemanthamine (HA) and sodium butyrate (NaB) are promising candidates for chemotherapy as a treatment for cancer. PURPOSE: We aimed to determine the anticancer potential of HA and NaB, alone and in combination, in A2780 ovarian cancer cells and concurrently investigated anticancer potential in contrast to non-cancer human MRC-5 fibroblasts. METHODS: Antiproliferative effects were determined by WST-1 assay and by Trypan blue exclusion staining. Cell cycle distributions were studied by flow cytometry and protein levels were determined by Western blotting. RESULTS: The combination of HA and NaB caused a significant decrease in the proliferation of A2780 cells compared to the stand-alone treatment of cells by HA or NaB. This effect was less pronounced in non-cancer MRC-5 fibroblasts. In the later intervals, the number of A2780 living cells was strongly decreased by treatment using a combination of NaB and HA. This simultaneous application had no considerable effect in MRC-5 fibroblasts. The combination of NaB and HA led to the suppression of cells in the G1 phase and caused an accumulation of cells in the S and G2 phase in comparison to those treated with NaB and HA alone. Treatment of cells with NaB alone led to the activation of proteins regulating the cell cycle. Notably, p21WAF1/Cip1 was upregulated in both A2780 and MRC-5 cells, while checkpoint kinases 1 and 2 were activated via phosphorylation only in A2780 cells. Unexpectedly, NaB in combination with HA suppressed the phosphorylation of Chk2 on threonine 68 and Chk1 on serine 345 in A2780 cells and downregulated p21WAF1/Cip1 in both tested cell lines. The sensitization of cells to HA and NaB treatment seems to be accompanied by increased histone acetylation. NaB-induced acetylation of histone H3 and H4 and histone acetylation increased markedly when a combination of NaB and HA was applied. Whereas the most prominent hyperacetylation after HA and NaB treatment was observed in A2780 cells, the acetylation of histones occurred in both cell lines. CONCLUSION: In summary, we have demonstrated the enhanced activity of HA and NaB against A2780 cancer cells, while eliciting no such effect in non-cancer MRC-5 cells. PMID- 28991640 TI - The isoflavonoid tectorigenin has better antiplatelet potential than acetylsalicylic acid. AB - BACKGROUND: One reason for the lower incidence of cardiovascular diseases in Asian countries may be the high intake of isoflavonoids and their antiplatelet effects may be an important factor. To date, there is limited comparison of a range of isoflavonoids and knowledge of their effects at different levels of platelet aggregation. PURPOSE: To screen the antiplatelet effects of a number of isoflavonoids on the arachidonic acid based aggregation pathway and investigate how the antiplatelet activity might occur. METHODS: The antiplatelet effects were first screened in whole human blood where platelet aggregation was induced by arachidonic acid. Further analysis was targeted at search of the mechanism of action. RESULTS: Thirteen of the eighteen tested isoflavonoids had significant inhibitory effect on platelet aggregation in whole human blood. Genistein had the same potency as clinically used acetylsalicylic acid (ASA) while tectorigenin was clearly stronger than ASA. Further analyses showed that the effect of tectorigenin was not based on inhibition of cyclooxygenase-1 in contrast to ASA or thromboxane synthase but by competitive antagonism at thromboxane receptors. CONCLUSION: Tectorigenin is a more potent antiplatelet compound than ASA and thus an interesting substance for further testing. PMID- 28991641 TI - Cardioprotection of stevioside on stunned rat hearts: A mechano-energetical study. AB - BACKGROUND: The sweetener and hypoglycemic properties of stevioside (STV) are well known, as the main component of the plant Stevia rebaudiana. Given its extensive use in diabetic patients, it was of interest to evaluate its effects on the most frequent cardiovascular disease, the coronary insufficiency. PURPOSE: To study whether STV could be cardioprotective against ischemia-reperfusion (I/R) in a model of "stunning" in rat hearts. STUDY DESIGN: A preclinical study was performed in isolated hearts from rats in the following groups: non-treated rats whose hearts were perfused with STV 0.3 mg/ml and their controls (C) exposed to either moderate stunning (20 min I/45 min R) or severe stunning (30 min I/45 min R), and a group of rats orally treated with STV 25 mg/kg/day in the drink water during 1 week before the experiment of severe stunning in the isolated hearts were done. METHODS: The mechano-calorimetrical performance of isolated beating hearts was recorded during stabilization period with control Krebs perfusion inside a calorimeter, with or without 0.3 mg/ml STV before the respective period of I/R. The left ventricular maximal developed pressure (P) and total heat rate (Ht) were continuously measured. RESULTS: Both, orally administered and perfused STV improved the post-ischemic contractile recovery (PICR, as % of initial control P) and the total muscle economy (P/Ht) after the severe stunning, but only improved P/Ht in moderate stunning. However, STV increased the diastolic pressure (LVEDP) during I/R in both stunning models. For studying the mechanism of action, ischemic hearts were reperfused with 10 mM caffeine-36 mM Na+-Krebs to induce a contracture dependent on sarcorreticular Ca2+ content, whose relaxation mainly depends on mitochondrial Ca2+ uptake. STV at 0.3 mg/ml increased the area under-curve of the caffeine-dependent contracture (AUC-LVP). Moreover, at room temperature STV increased the mitochondrial Ca2+ uptake measured by Rhod-2 fluorescence in rat cardiomyocytes, but prevented the [Ca2+]m overload assessed by caffeine-dependent SR release. CONCLUSIONS: Results suggest that STV is cardioprotective against I/R under oral administration or direct perfusion in hearts. The mechanism includes the regulation of the myocardial calcium homeostasis and the energetic during I/R in several sites, mainly reducing mitochondrial Ca2+ overload and increasing the sarcorreticular Ca2+ store. PMID- 28991642 TI - Retraction notice to "RETRACTED: 6-OHDA-induced apoptosis and mitochondrial dysfunction are mediated by early modulation of intracellular signals and interaction of Nrf2 and NF-kappaB factors" [Toxicology (2013) 109 - 119]. PMID- 28991643 TI - The Effects of Aging on Lung Structure and Function. AB - Growth of the segment of the population older than 65 years has led to intensified interest in understanding the biology of aging. This article is focused on age-related alterations in lung structure that produce predictable changes in physiologic function, both at rest and during exercise. Increased insight into the physiology of the healthy aging lung should ultimately lead to improved methods of lung function assessment in the elderly (defined as those older than 65 years) as well as better understanding of the manifestations and possibly even the treatment of geriatric lung disease. PMID- 28991645 TI - Lung Diseases of the Elderly: Cellular Mechanisms. AB - Natural lung aging is characterized by molecular and cellular changes in multiple lung cell populations. These changes include shorter telomeres, increased expression of cellular senescence markers, increased DNA damage, oxidative stress, apoptosis, and stem cell exhaustion. Aging, combined with the loss of protective repair processes, correlates with the development and incidence of chronic respiratory diseases, including idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease. Ultimately, it is the interplay of age-related changes in biology and the subsequent responses to environmental exposures that largely define the physiology and clinical course of the aging lung. PMID- 28991646 TI - Epidemiology of Lung Disease in Older Persons. AB - Older persons frequently report respiratory risk factors and symptoms and have a high prevalence of symptomatic lung disease, most commonly obstructive airway disease, interstitial lung disease, and lung cancer. Notably, coexisting nonrespiratory risk factors are also prevalent and may misidentify or modify respiratory diagnoses and their clinical course. PMID- 28991644 TI - Inflammaging and the Lung. AB - With the coming of the "silver tsunami," expanding the knowledge about how various intrinsic and extrinsic factors affect the immune system in the elderly is timely and of immediate clinical need. The global population is increasing in age. By the year 2030, more than 20% of the population of the United States will be older than 65 years of age. This article focuses on how advanced age alters the immune systems and how this, in turn, modulates the ability of the aging lung to deal with infectious challenges from the outside world and from within the host. PMID- 28991647 TI - Evaluation of Dyspnea in the Elderly. AB - Dyspnea is due to an imbalance between the demand to breathe and the ability to breathe. The prevalence is ~30% for those 65 years or older with walking on a level surface or up an incline. Dyspnea is a strong predictor of mortality in elderly individuals. Anemia, cardiovascular disease, deconditioning, psychological disorders, and respiratory diseases are common causes of dyspnea. Initial treatments to relieve breathing discomfort should be directed toward improving the pathophysiology of the underlying disease. Simple and inexpensive strategies to relieve dyspnea are available. This article provides an update on the evaluation of chronic dyspnea in elderly individuals. PMID- 28991648 TI - Asthma in the Elderly. AB - The older population has seen the greatest increase in the prevalence of current asthma in recent years. Asthma may begin at any age and when it occurs at an advanced as opposed to a young age, it is often nonatopic, severe, and unremitting. Unfortunately, geriatric-specific guidelines are not available for the diagnosis and treatment of asthma. However, with objective monitoring, avoidance of asthma triggers, appropriate pharmacotherapy, and patient education, the disease can be managed successfully. PMID- 28991649 TI - Chronic Obstructive Pulmonary Disease in Elderly Patients. AB - Chronic obstructive pulmonary disease (COPD) is prevalent in the elderly population, with high impact on quality of life, morbidity, and mortality. The diagnosis is usually made based on symptoms and spirometry values that support the presence of airflow obstruction. However, the condition is frequently underdiagnosed. COPD is associated with premature aging and several other medical conditions that can partially explain its underdiagnosis and management. There are several pharmacologic and nonpharmacologic interventions proven to be effective in ameliorating the symptoms of COPD. Appropriate drug delivery and reduction of side effects is also pivotal in the management of patients with COPD. PMID- 28991650 TI - Pulmonary Vascular Diseases in the Elderly. AB - Pulmonary hypertension is a pathologic hemodynamic condition defined by a mean pulmonary arterial pressure of 25 mm Hg or greater at rest. Because of age associated stiffening of the heart and the pulmonary vasculature and the higher prevalence in the elderly of comorbidities associated with the development of pulmonary hypertension, it is an increasingly common finding in this patient population. A right heart catheterization is necessary for the diagnosis and characterization of pulmonary hypertension. The general management is to treat the underlying conditions responsible for the development of the disorder. Pulmonary vasodilators are indicated in patients with pulmonary arterial hypertension. PMID- 28991651 TI - Lung Cancer in the Older Patient. AB - Cancers of the lung and bronchus are the leading cause of cancer deaths in men and women in the United States, and two-thirds of new lung cancer cases are diagnosed in patients over age 65. There are few dedicated clinical trials in the elderly, leading to both undertreatment and overtreatment biases. Even fit older adults experience age-related decline in physiologic reserve, and additional issues of polypharmacy, geriatric syndromes, and inadequate social support are not uncommon, leading to disparities in treatment and survival. This review discusses the challenges in balancing benefits and harms in management of lung cancer in elderly patients. PMID- 28991652 TI - Sleep in the Elderly: Unanswered Questions. AB - Sleep normally changes with aging, with implications for healthy elderly individuals as well as for those with disease states. Less slow wave sleep (deep sleep) is expected, along with more awakenings, and a tendency toward earlier sleep times. Rapid eye movement sleep behavior disorder is seen primarily in elderly individuals, and it often represents the earliest sign of a chronic and progressive neurologic disease. Complaints of difficulty initiating and maintaining sleep (insomnia) become more common with aging. Irregular breathing with sleep also becomes more common, with an increased Apnea Hypopnea Index that may not always be clinically important. PMID- 28991653 TI - Comorbidities of Lung Disease in the Elderly. AB - Comorbidities are common in elderly individuals with chronic respiratory diseases. They can affect disease manifestations and severity and can even impact management. Comorbidities can affect the treatment of the lung disease, particularly because of the interaction with the respiratory drugs. Thus, a multidimensional approach with multidisciplinary intervention is suggested for elderly respiratory patients, switching from a disease-oriented scheme to a dysfunction-oriented approach. Unfortunately, older individuals are often excluded from clinical trials because of advanced age and comorbidities. This article reviews the role of comorbidities in the management of respiratory diseases in the elderly. PMID- 28991654 TI - Pulmonary Disease in the Aging Patient. PMID- 28991655 TI - Apparent diffusion coefficient reduction might be a predictor of poor outcome in patients with posterior reversible encephalopathy syndrome. AB - It is thought that posterior reversible encephalopathy syndrome (PRES) is both clinically and radiologically reversible. However, its reversible nature has been challenged based on reports of permanent neurological impairments. The factors that predict the development of irreversible neurological impairment are still unclear. In the present study, we investigated clinical manifestations, laboratory findings, and neuroradiological images to identify predictors of functional outcomes in PRES. We investigated 23 PRES patients. Apparent diffusion coefficient (ADC) reduction was observed in 4 patients in the poor outcome group, whereas no patients presented ADC reduction in the favourable outcome group (p<0.01). Further studies are warranted to evaluate the association between ADC reduction and functional outcome after PRES. PMID- 28991656 TI - 18F-FDG PET/MRI in cryptogenic new-onset refractory status epilepticus: a potential marker of disease location, activity and prognosis? PMID- 28991658 TI - Highly asymmetric and subacutely progressive motor weakness with unilateral T2 weighted high intensities along the pyramidal tract in the brainstem in adrenomyeloneuropathy. PMID- 28991657 TI - Quantitative analysis of brain atrophy in patients with xeroderma pigmentosum group A carrying the founder mutation in Japan. AB - INTRODUCTION: Xeroderma pigmentosum (XP) is an inherited congenital disease presenting with dermatological and neurological manifestations. In Japan, XP complementation group A (XP-A) is most frequently observed in eight clinical subtypes, and the homozygous founder mutation, IVS3-1G>C in XPA, suffer from severe manifestations including progressive brain atrophy since childhood. In this study, we used magnetic resonance imaging (MRI) and applied volumetric analysis to elucidate the start and the progression of the brain atrophy in these patients. MATERIAL AND METHODS: Twelve Japanese patients with XP-A carrying the founder mutation and seven controls were included. MRI was performed for each patient once or more. Three-dimensional T1 weighted images were segmented to gray matter, white matter, and cerebrospinal fluid, and each volume was calculated. RESULTS: Conventional MRI demonstrated progressive whole brain atrophy in patients with XP-A. Moreover, volumetric analysis showed that reductions of total gray matter volumes (GMV) and total brain volumes (TBV) started at the age of five. The slope of reduction was similar in all cases. The GMV and TBV values in controls were higher than those in XP-A cases after the age of five. CONCLUSIONS: This is the first quantitative report presenting with the progression of brain atrophy in patients with XP-A. It is revealed that the brain atrophy started from early childhood in Japanese patients with XP-A carrying the homozygous founder mutation. PMID- 28991659 TI - Proposed cut scores for tests of the Brief International Cognitive Assessment of Multiple Sclerosis (BICAMS). AB - OBJECTIVE: Cognitive impairment (CI) is common in multiple sclerosis (MS). An international consensus committee developed the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) to screen for CI commonly seen in MS. BICAMS cut scores would allow clinicians to, efficiently and effectively, identify patients with possible CI and could aid in clinical decision-making. The aim of this study was to establish cut scores for the neuropsychological tests of the BICAMS. METHODS: This study utilized data collected from MS Centers in the United States. ROC curve analysis identified cut scores yielding the best balance of sensitivity and specificity. We tested two definitions of impairment: 1.5 and 2 standard deviations (SD) below the normative mean. RESULTS: All cut scores yielded excellent or good sensitivity and specificity for identifying impaired cognitive performance. The following cut scores yielded the best balance between sensitivity and specificity: On the Symbol Digit Modalities Test, 44 for 1.5 SD below the mean and 38 for 2 SD below the mean; on the California Verbal Learning Test - II learning trials, 39 (1.5 SD) and 35 (2 SD); and on the Brief Visuospatial Memory Test-Revised learning trials, 17 (1.5 SD) and 16 (2 SD). CONCLUSIONS: Cut scores can accurately identify cognitive impairment on all subtests of the BICAMS. Use of cut scores may improve the efficiency of screening for cognitive impairment by reducing administrative burden and simplifying interpretation. PMID- 28991660 TI - Effects of educational television commercial on pre-hospital delay in patients with ischemic stroke wore off after the end of the campaign. PMID- 28991661 TI - Behavioral and affective features of amyotrophic lateral sclerosis patients. AB - Evaluating the cognitive and behavioral features in amyotrophic lateral sclerosis (ALS) patients is important for therapy and care. Fifty-seven ALS, 5 ALS with the behavioral variant of frontotemporal dementia (FTD) (ALS-FTD), 12 FTD patients, and 35 control subjects were evaluated by 10 different tests for cognitive and behavioral (mini-mental state examination (MMSE), Hasegawa dementia rating scale revised (HDS-R), frontal assessment battery (FAB), Montreal cognitive assessment (MoCA), ALS-frontotemporal dementia-Questionnaire (ALS-FTD-Q), and anosognosia scale), affective (depression, apathy, and behavioral and psychological symptoms of dementia (BPSD)), and activities of daily living (ADL) assessments. The motor functions of ALS patients were evaluated by ALS functional rating scale - revised (ALSFRS-R) and modified Norris scale. ALS-FTD-Q scores showed intermediate behavioral disturbances of ALS patients between ALS-FTD and FTD patients and control subjects, but FAB, MoCA, and anosognosia scales did not. Both FAB and MoCA scores were significantly correlated with MMSE and HDS-R in ALS patients, but ALS-FTD-Q was not. ALS-FTD-Q score was significantly correlated with ALSFRS R, apathy, BPSD, and ADL scores in ALS patients. Thus, in ALS patients, both FAB and MoCA tests were useful to assess frontal cognitive impairments, while ALS-FTD Q was useful to detect mild behavioral and affective disturbances. PMID- 28991662 TI - Dissociation findings between short-term and long-term memory in autoimmune limbic encephalitis. PMID- 28991663 TI - A nationwide survey of familial syringomyelia in Japan. PMID- 28991664 TI - IncobotulinumtoxinA treatment of facial nerve palsy after neurosurgery. AB - BACKGROUND: This study evaluates the effect of incobotulinumtoxinA in the acute and chronic phases of facial nerve palsy after neurosurgical interventions. METHODS: Patients received incobotulinumtoxinA injections (active treatment group) or standard rehabilitation treatment (control group). Functional efficacy was assessed using House-Brackmann, Yanagihara System and Sunnybrook Facial Grading scales, and Facial Disability Index self-assessment. RESULTS: Significant improvements on all scales were seen after 1month of incobotulinumtoxinA treatment (active treatment group, r<0.05), but only after 3months of rehabilitation treatment (control group, r<0.05). At 1 and 2years post-surgery, the prevalence of synkinesis was significantly higher in patients in the control group compared with those receiving incobotulinumtoxinA treatment (r<0.05 and r<0.001, respectively). CONCLUSIONS: IncobotulinumtoxinA treatment resulted in significant improvements in facial symmetry in patients with facial nerve injury following neurosurgical interventions. Treatment was effective for the correction of the compensatory hyperactivity of mimic muscles on the unaffected side that develops in the acute period of facial nerve palsy, and for the correction of synkinesis in the affected side that develops in the long-term period. Appropriate dosing and patient education to perform exercises to restore mimic muscle function should be considered in multimodal treatment. PMID- 28991665 TI - Spinal cord anteroposterior atrophy in HAM/TSP: Magnetic resonance imaging and neuropathological analyses. AB - To evaluate the spinal cord atrophy that occurs in HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), we conducted magnetic resonance imaging (MRI) and pathological analyses. In the MRI study, 15 patients with HAM/TSP and 20 age-matched normal control subjects were enrolled. Anteroposterior and transverse distances and cross-sectional areas were measured and calculated at the C2, C4, C6, T2, and T6 vertebral levels. In the pathological study, spinal cord autopsy specimens were compared between a HAM/TSP case and an adult T cell leukemia/lymphoma case. In both the MRI and pathological studies, HAM/TSP spinal cords demonstrated more severe atrophy in the anteroposterior direction than those of controls. The spinal cord atrophy and pathological changes in HAM/TSP occurred predominantly in the white matter, especially in the lateral columns. This is the first report indicating spinal cord atrophy in the anteroposterior direction using MRI. In pathological analysis, atrophy and pathological changes were prominent in areas of the spinal cord with slow blood flow. Hemodynamic and anatomical factors are speculated to be among the main mechanisms of atrophy in the anteroposterior direction. PMID- 28991666 TI - Educational attainment and motor burden in advanced Parkinson's disease - The emerging role of education in motor reserve. AB - OBJECTIVE: To explore the relationship of motor burden and educational attainment in patients with advanced stage PD. MATERIALS AND METHODS: We included 102 consecutive patients who underwent a complete evaluation for DBS surgery, including detailed neuropsychological testing and UPDRSIII in a standardized Levodopa challenge. Years of education (YoE) were calculated as the highest grade attained in secondary school plus years for post-secondary training. RESULTS: The OFF medication UPDRS-III score was associated with YoE (p=0.006; t=-2.82) and age (p=0.007; t=-2.75) in our multivariable linear regression model even while including disease duration (p=0.8; t=0.21), presence of mild cognitive impairment (MCI) (p=0.9; t=0.16) or current IQ (p=0.2; t=1.25) as additional covariables. In a subgroup of 60 patients two years after DBS, the ON/ON UPDRS score was associated with YoE (p=0.01; t=-2.42) and diagnosis of PD dementia (p=0.05, t=1.95), while age (p=0.08, t=1.75), disease duration (p=0.6t=0.48) and LEDD (p=0.3; t=1.05) showed no significant association to ON/ON UPDRS score. CONCLUSIONS: We found an inverse correlation between years of education and lower (better) UPDRS -III motor score after adjusting for important covariables. Education may lead to an increased ability to compensate disturbances in basal ganglia circuits affecting not only for cognitive, but also for motor aspects of PD. Thus, educational attainment may play an important role in the concept of motor reserve. PMID- 28991667 TI - Coexistence of transthyretin- and Abeta-type cerebral amyloid angiopathy in a patient with hereditary transthyretin V30M amyloidosis. PMID- 28991668 TI - SMART syndrome with cerebral angiographic abnormalities - A case report. PMID- 28991669 TI - Noninvasive fractional flow in intracranial atherosclerotic stenosis: Reproducibility, limitations, and perspectives. PMID- 28991670 TI - Follow-on products for treatment of multiple sclerosis in Latin America: An update. AB - Both proprietary and non-proprietary medicines are expected to undergo rigorous pre-approval testing and both should meet stringent health authority regulatory requirements related to quality to obtain approval. Non-proprietary (also known as copy or generic) medicines, which base their authorization and use on the proprietary documentation and label, are often viewed as a means to help lower cost and thus increase patient access. If these medicines fail to meet quality standards, such as good manufacturing practice and bioequivalence (in humans), they are then defined as substandard copies and can pose serious risks to patients in terms of safety and efficacy. Availability of this type of compounds is more prevalent in regions where health authorities do not enforce registration regulations as stringent as those of the Food and Drug Administration, European Medicines Agency, or World Health Organization, including preestablished quality standard requirements. This article focuses on non-proprietary medicines for multiple sclerosis, that are not identical to proprietary versions and could thus fail to meet efficacy or have different impact on the safety of patients with multiple sclerosis. PMID- 28991671 TI - Delayed elevation of plasma brain natriuretic peptide as a cue to diagnosis of atrial fibrillation in cryptogenic stroke: A case report. PMID- 28991672 TI - Clinical profiles associated with LRRK2 and GBA mutations in Brazilians with Parkinson's disease. AB - BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder characterized by remarkable phenotypic variability. Accumulated evidence points that the manifestation of PD clinical signs might be differentially modified by genetic factors, as mutations in LRRK2 and GBA genes. In this sense, the clarification of the genotype-phenotype correlations in PD has important implications in predicting prognosis and can contribute to the development of specific therapeutic approaches. METHODS: Here, we conducted the first comparative analysis of motor and non-motor features in 17 LRRK2 and 22 GBA mutation carriers and 93 non-carriers unrelated PD patients from Brazil, a highly admixed population. RESULTS: Significant differences were found between the three groups. LRRK2 PD patients presented more occurrence of familiar history. Resting tremor was observed in a lower frequency in GBA mutation carries. In contrast, gait freezing and dysautonomia was present in lower frequencies in LRRK2 carriers. Besides that, LRRK2 and GBA mutation carriers showed a higher incidence of depressive symptoms and a younger age at onset, when compared to non-carriers. CONCLUSION: Our results suggest that specific mutations in GBA and LRRK2 influence the clinical signs of the disease, with significant implications for handling of specific patient groups. PMID- 28991673 TI - Mortality and morbidity among hospitalized adult patients with neurological diseases in Cameroon. AB - BACKGROUND: There is inadequate information on the morbidity and mortality (M&M) from neurological diseases in sub-Saharan Africa. OBJECTIVE: To record the M&M from neurological diseases in adults in Cameroon from 2013 to 2015 using a registry and surveillance from two urban health care centers. METHODS: Records from all adult admissions from two urban hospitals over a two year period were reviewed. Adult cases with neurological diagnosis as the main cause for admission were identified. The neurological diagnosis was made by a neurologist in all cases. Variables analyzed were: demographics, neurological diagnosis, medical history, medical center characteristics, morbidity and mortality (M&M). Neurological diseases were classified according to ICD-10. RESULTS: Among the 2225 neurological admissions of adults, death from neurological disease was recorded in 423 patients (19.01%), and disability in 819 of the survivors (53.6%). The factors that were significantly associated with death in the multivariate analysis were age, history of ischemic cardiac disease, and neurological diagnoses of CNS infection, cerebrovascular disease, and CNS tumor. Similarly, factors associated with disability were medical history of HIV, and cerebrovascular disease, and neurological diagnoses of cerebrovascular disease and CNS tumor. Higher educational level and epilepsy were associated with less disability. CONCLUSIONS: As expected in this sample, older patients with neurological diseases had more M&M. Morbidity was inversely associated with education, which given that cerebrovascular disease is by far the most common cause of morbidity, indicates the power of risk factor control in preventing neurological disability. PMID- 28991674 TI - Body composition and adipokines plasma levels in patients with myasthenia gravis treated with high cumulative glucocorticoid dose. AB - This study aimed to evaluate changes in body composition, i.e. overweight, obesity, fat accumulation and low lean body mass and plasma levels of adipokines in patients with MG. The study enrolled 80 patients with MG, and 62 controls. Body fat mass and body lean mass was analyzed by dual-energy X-ray absorptiometry technique (DXA). Plasma levels of leptin were analyzed by Luminex(r) and adiponectin and resistin were analyzed by ELISA. The mean age of patients with MG was 41.9years, with 13.5years of length of illness, and mean cumulative dose of glucocorticoids 38,123mg. Our results showed that the frequency of obesity is higher in MG patients than in controls, and patients with MG presented higher body fat mass, android body adiposity and total body fat than controls. MG patients presented lower levels of resistin and higher levels of leptin in comparison with controls. There were no differences in the plasma levels of adiponectin. Higher total body fat and lower body lean mass were associated with increased severity of MG symptoms. This result points to the relevance of estimation of body composition in planning long-term care of MG patients. PMID- 28991675 TI - Sodium butyrate exerts protective effect against Parkinson's disease in mice via stimulation of glucagon like peptide-1. AB - Sodium butyrate (NaB) has exhibited protective activity in neurological disorders. Here, we investigated the neuroprotective effect and potential mechanisms of NaB in a mouse model of Parkinson's disease (PD). A mouse was intraperitoneally treated with MPTP (30mg/kg) for 7 consecutive days to induce PD model and NaB (200mg/kg) was intragastrically treated for 3weeks. The behavioral tests were then conducted. Dopaminergic degeneration was evaluated by western blot and immunohistochemistry of tyrosine hydroxylase (TH) in the SN. Brain damage was assessed by histologic (Nissl staining for cell death), apoptosis associated protein and tight junction (TJ) proteins studies. Meanwhile, the levels of colonic glucagon-like peptide-1 (GLP-1) and cerebral GLP-1 receptor (GLP-1R) expression were assessed. Our results showed that NaB improved neurobehavioral impairment including cognitive behavior and coordination performance. Moreover, NaB treatment prevented the MPTP-induced dopaminergic degeneration and decreased expression level of TH in the striatum. NaB treatment attenuated the PD-associated disruption of BBB by upregulation of Occludin and zonula occludens (ZO)-1. In addition, NaB resulted in increased level of Bcl-2 and decreased level of Bax. Particularly, NaB-treated mice with PD exhibited increased colonic GLP-1 level as well as upregulation of brain GLP-1R expression compared with PD group. Our findings suggest that NaB has potential as a novel therapeutic for treatment of PD, and its mechanism was associated with stimulating colonic GLP-1secretion. PMID- 28991676 TI - Sulfonylurea drug pretreatment and functional outcome in diabetic patients with acute intracerebral hemorrhage. AB - PURPOSE: Intracerebral hemorrhage (ICH) is associated with poor clinical outcome and high mortality. Sulfonylurea (SFU) use may be a viable therapy for inhibiting sulfonylurea receptor-1 and NCCa-ATP channels and reducing perihematomal edema and blood-brain barrier disruption. We sought to evaluate the effects of prehospital SFU use with outcomes in diabetic patients with acute ICH. METHODS: We retrospectively analyzed a cohort of diabetic patients presenting with acute ICH at a tertiary care center. Study inclusion criteria included spontaneous ICH etiology and age>18years. Baseline clinical severity was documented using ICH score. Hematoma volumes (HV) on admission were calculated using ABC/2 formula. Unfavorable functional outcome was documented as discharge modified Rankin Scale scores 2-6. RESULTS: 230 diabetic patients with acute ICH fulfilled inclusion criteria (mean age 64+/-13years, men 53%). SFU pretreatment was documented in 16% of the study population. Patients with SFU pretreatment had significantly (p<0.05) lower median ICH-scores (0, IQR: 0-2) and median admission HV (4cm3, IQR: 1-12) compared to controls [ICH-score: 1 (IQR: 0-3); HV: 9cm3 (IQR: 3-20)]. SFU pretreatment was independently (p=0.033) and negatively associated with the cubed root of admission HV (linear regression coefficient: -0.208; 95%CI: -0.398 to -0.017) in multiple linear regression analyses adjusting for potential confounders. Pretreatment with SFU was also independently (p=0.033) associated with lower likelihood of unfavorable functional outcome (OR=0.19; 95%CI: 0.04 0.88) in multivariable logistic regression models adjusting for potential confounders. CONCLUSION: SFU pretreatment may be an independent predictor for improved functional outcome in diabetic patients with acute ICH. This association requires independent confirmation in a large prospective cohort study. PMID- 28991677 TI - Hurst revisited: Are symptoms and signs of functional motor and sensory disorders "dependent on idea"? AB - INTRODUCTION: Symptoms and signs of functional (psychogenic) motor and sensory disorder are often said to be dependent on the patients' idea of what symptoms should be, rather than anatomy and physiology. This hypothesis has however rarely been tested. MATERIALS AND METHODS: Inspired by a brief experiment carried out in 1919 by neurologist Arthur Hurst we aimed to assess the views of healthy non medical adults towards paralysis and numbness and their response to tests for functional disorders when asked to pretend to have motor and sensory symptoms. RESULTS: When subjects were asked to pretend they had a paralysed arm 80% thought there would be sensory loss. Of these 60% thought it would have a circumferential (functional) distribution at the wrist, elbow or shoulder. Hoover's sign of functional weakness was only positive in 75% of patients pretending to have leg paralysis with 23% maintaining weakness of hip extension in the feigned weak leg, a rare finding in neurological practice. 20% of subjects managed to continue having their feigned tremor during the entrainment test. 52% of subjects thought there was asymmetry of a tuning fork across their forehead even when no prior instruction had been given. CONCLUSIONS: The study confirmed Hurst's finding that non-medical people generally expect sensory loss to go along with paralysis, especially if the examiner suggests it. When present, it usually conforms to functional patterns of sensory loss. Clinical tests for functional and motor disorders appear to behave somewhat differently in patients asked to pretend to have symptoms suggesting that larger more detailed studies would be worthwhile. PMID- 28991678 TI - The Anna O. mystery: Hysteria or neuro-tuberculosis? PMID- 28991679 TI - Brainstem cytokine changes in healthy ageing and Motor Neurone Disease. AB - Neuroinflammation is linked to healthy ageing, but its role in the development of age-related neurodegenerative diseases is unclear. In this pilot study we used a multiplex assay approach to compare 27 cytokines in 6 young adult and 6 ageing control brainstems with those in 6 MND brainstems. We report that healthy ageing is associated with significantly increased brainstem levels of IL-1beta, IP-10 and MIP-1beta which co-localise immunocytochemically to astrocytes. MND brainstem is also characterised by a general increase in both pro- and anti-cytokine levels, but fails to show the expected age-related increase in MIP-1beta and IP 10. This pilot study is the first to show that MND is associated with a failure of specific features of the normal age-related neuroinflammatory process. We suggest that our pilot data indicates that neuroinflammation during healthy ageing may not always be detrimental to motoneuronal survival and that age related neurodegenerative diseases, such as MND, may instead result from defective neuroinflammation. PMID- 28991680 TI - Capsular warning syndrome: The role of blood pressure. PMID- 28991681 TI - Successful treatment of recurrent primary CNS vasculitis with etanercept. PMID- 28991682 TI - Potential role of tele-rehabilitation to address barriers to implementation of physical therapy among West African stroke survivors: A cross-sectional survey. AB - BACKGROUND: The greatest burden from stroke-related disability is borne by Low and-Middle Income countries (LMICs) where access to rehabilitation after stroke is severely challenged. Tele-rehabilitation could be a viable avenue to address unmet rehabilitation needs in LMICs. OBJECTIVES: To assess the burden of post stroke physical deficits, rates of utilization of physiotherapy services, and perceptions of tele-rehabilitation among recent Ghanaian stroke survivors. METHODS: Using a consecutive sampling strategy, 100 stroke survivors attending an outpatient Neurology clinic in a Ghanaian tertiary medical center were enrolled into this cross-sectional study. After collecting basic demographic data, clinical history on stroke type, severity and level of disability, we administered the validated 20-item Functional Independence Measure questionnaire to evaluate functional status of study participants and an 8-item questionnaire to assess participants' attitudes towards telemedicine administered rehabilitation intervention. RESULTS: Mean+/-SD age of study participants was 57.2+/-13.3years of which 51.0% were males with a mean duration of stroke of 1.3+/-2.2years. 53% had Modified Rankin scores of >=3, 57% were fully independent and only 27% reported utilizing any physiotherapy services. Barriers to access to physiotherapy included financial constraints due to cost of physiotherapy services and transportation as well as premature discharge from physiotherapy to avoid overburdening of available physiotherapy services. These factors led to the limited provision of rehabilitative therapy. Participants held positive views of the potential for tele-rehabilitation interventions (80-93%). However, while 85% owned mobile phones, only 35% had smart phones. CONCLUSION: Despite, a high burden of residual disability, only about 1 out of 4 stroke patients in this Ghanaian cohort was exposed to post-stroke physiotherapy services, largely due to relatively high costs and limited health system resources. These Ghanaian stroke patients viewed the potential role of Tele-rehabilitation as positive, but this promising intervention needs to be formally tested for feasibility, efficacy and cost-effectiveness. PMID- 28991683 TI - A new PLA2G6 mutation in a family with infantile neuroaxonal dystrophy. AB - Phospholipase A2-associated neurodegeneration (PLAN), a syndrome of Neurodegeneration with Brain Iron Accumulation (NBIA), is an autosomal recessive disorder caused by mutations in PLA2G6 gene. This gene encodes a calcium independent group VI phospholipase A2 (iPLA-VI) critical in cell membrane homeostasis. PLAN syndrome encompasses a group of phenotypes with a different age of onset: classic infantile neuroaxonal dystrophy (INAD), atypical neuroaxonal dystrophy of childhood-onset (atypical NAD) and adult-onset PLA2G6-related dystonia-parkinsonism (PARK14). INAD is a severe progressive psychomotor disorder characterized by the presence of axonal spheroids throughout the central and peripheral nervous system. Here we report clinical, genetic and histopathological findings of an INAD consanguineous-family from Senegal. Sanger sequencing analysis revealed a new homozygous PLA2G6-mutation in the proband (c.1483C>T) and the co-segregation of the mutation in this family. Electron microscopy on skin biopsy showed degenerated axons confirming the phenotype. This study contributes to enrich the landscape of PLA2G6-associated INAD mutations and enforce the genotype-phenotype correlation. PMID- 28991684 TI - Vitamin D deficiency is associated with disability and disease progression in multiple sclerosis patients independently of oxidative and nitrosative stress. AB - The aim of this study was to assess vitamin D status in patients with multiple sclerosis (MS) and to evaluate whether it was associated with oxidative and nitrosative stress (O&NS) markers and disability. This study included 137 patients with MS and 218 healthy controls. The markers evaluated were serum levels of 25-hydroxyvitamin D, lipid hydroperoxides, advanced oxidation protein products (AOPP), nitric oxide metabolites (NOx), and total radical-trapping antioxidant parameter TRAP/UA. Patients with 25(OH)D<20ng/mL showed higher EDSS (p=0.016), MSSS (p=0.005) and lower AOPP (p=0.046) than those with 25(OH)D>=20ng/mL. After the binary logistic regression analyses, EDSS and MSSS remained significantly associated with vitamin D deficiency. We showed that lower levels of 25(OH)D were associated with higher EDSS and MSSS independently of variables such as O&NS, age, sex, body mass index, ethnicity, MS therapy, use of interferon beta, and clinical forms of MS (odds ratio: 1.380, 95% confidence interval 1.030-1.843, p=0.031). Moreover, the study showed an association between serum levels of 25(OH)D and EDSS (r2=0.115, p=0.002), demonstrating that 25(OH)D may contribute with 11.5% of increase in EDSS. Our results suggest that vitamin D deficiency may be considered one of the predictors of the disability in MS patients, independently of their redox status and influence the progression of disability in MS. PMID- 28991685 TI - Polymyositis induced by PD-1 blockade in a patient in hepatitis B remission. PMID- 28991686 TI - Period3 gene in disorder of consciousness: The role of neuroimaging in understanding the relationship between genotype and sleep. A brief communication. AB - BACKGROUND: Several methodologies including neuroimaging and sleep evaluation are being developed to complement the clinical bedside examinations in patients with disorder of consciousness (DOC). Recently, we demonstrated a possible association between Period3 (Per3) variable number tandem repeat (VNTR) polymorphism and functional impairment of DOC patients, speculating a possible role of this gene in sleep regulation. AIM: To assess whether the degree of structural and metabolic damage of the main brain areas involved in the sleep generation and homeostasis may influence the different outcome of DOC patients carrying the Per35/5 genotype in comparison to Per34/4 ones. METHODS: For the present study, we reviewed 44 DOC patients from the Coma Research Centre of the Fondazione IRCCS Istituto Neurologico "C. Besta" of Milan. All patients underwent to polysomnographic sleep evaluation, cerebral structural magnetic resonance imaging (MRI) and 18F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) analysis. RESULTS: Our DOC patients presented a moderate anatomical (median score 2) and metabolic damage (median value 2.36 SUVmean) of the sleep areas at both MRI and FDG-PET evaluation. Total sleep time seemed to be higher in 5/5 genotype DOC patients (median value Per35/5, 221min, range 126-323min; median value Per34/4, 167min, range 36-477min; and median value Per34/5, 187min, range 29 422min). However, the MRI scores and FDG-PET values of whole brain, overall sleep areas, hypothalamus, midbrain and thalamus did not differ by genotype distribution. CONCLUSION: Although limited by the small sample size, our data might support the idea that Per3 genetic predisposition in DOC patients could affect impairment and residual cognitive functions through sleep homeostasis independently from structural and/or metabolic integrity of sleep areas. PMID- 28991687 TI - Cerebrospinal fluid total protein in idiopathic intracranial hypertension. AB - OBJECTIVE: To evaluate the relationship between CSF total protein concentration (CSF protein) and CSF opening pressure in idiopathic intracranial hypertension (IIH), and to explore the association of age, gender, race, BMI, and Humphrey visual field mean deviation (HVF MD) with CSF total protein. METHODS: The medical records of all IIH patients seen between 1989 and 2016 at one institution were systematically reviewed for demographics, CSF opening pressure, CSF contents, and HVF MD (at initial evaluation and most recent follow-up). Linear regression of CSF protein on CSF opening pressure was performed also considering BMI, age, gender, race, HVF MD, and year of lumbar puncture. RESULTS: We included 266 IIH patients (13 pre-pubertal children, 35 post-pubertal children, 218 adults). There was a negative linear association between CSF opening pressure and CSF protein: CSF protein decreased by 0.18mg/dL for each 1cm H2O increase in CSF opening pressure (p<0.001). After controlling for CSF opening pressure, mean CSF protein was 4.1mg/dL higher in white patients than in black patients (p<0.001). Multivariable analysis found that CSF opening pressure (p=0.007), white race (p<0.001), and HVF MD (most recent follow-up, worst eye, p=0.05) remained independently associated with CSF protein controlling for year of lumbar puncture and age. CONCLUSIONS: There was a negative association between CSF protein and CSF opening pressure. After controlling for CSF opening pressure, CSF protein was higher in white patients and unaffected by age, gender, or BMI. Our findings help clarify inconsistent results of prior studies, but do not really help clarify IIH pathophysiology. PMID- 28991688 TI - Postvoid residual predicts the diagnosis of multiple system atrophy in Parkinsonian syndrome. AB - OBJECTIVE: It is difficult to differentiate multiple system atrophy (MSA) from Parkinson's disease (PD) at least in the early stage. Urodynamic study (UDS) is useful in differentiating MSA from PD. We aimed to clarify which UDS parameter was useful in differentiating MSA from PD. METHODS: We retrospectively reviewed 273 cases and performed UDS and external anal sphincter electromyography (EAS EMG) in patients with MSA (n=182) and PD (n=91). We analyzed the utility of UDS parameters, including postvoid residuals (PVR), detrusor overactivity (DO), degree of bladder contraction, and mean duration of motor unit potentials (MUPs) in EAS-EMG, for differentiating MSA from PD. RESULTS: PVR>150ml during free-flow study strongly indicated MSA rather than PD (OR 8.723, 95% CI 2.612-29.130, p<0.001). 'Weak detrusor' also suggested MSA, but it was not a statistically significant indicator (OR 10.598, 95% CI 0.359-312.473, p=0.172). DO and neurogenic changes in EAS-EMG (mean duration of MUPs>10ms) did not significantly contribute to the differentiation of MSA from PD. CONCLUSIONS: PVR>150ml during free-flow study might be more useful than other UDS parameters in clinically differentiating MSA from PD. PMID- 28991689 TI - Intraoperative neuromonitoring loss in abnormal magnetic resonance imaging signal intensity from patients with cervical compressive myelopathy. AB - PURPOSE: Our objective of this study was to evaluate if cervical compressive myelopathy (CCM) patients with preoperative abnormal magnetic resonance imaging (MRI) might easily lead to intraoperative neuromonitoring (IONM) loss. METHOD: A consecutive series of 152 CCM patients who underwent cervical cord decompression were enrolled in this study between December 2013 and February 2017. All patients with abnormal MRI signal intensity were divided into 2 groups (group 1: T2-WIs hyperintensity; group 2: both T2-WIs hyperintensity and T1-WIs hypointensity). Relevant IONM changes were identified as significant transcranial motor evoked potentials (MEP) loss associated with surgical decompression of cervical cord. RESULTS: There were 121 patients in group 1, and then 6 cases showed IONM degeneration; 31 patients in group 2, and then 13 cases showed IONM degeneration (6/121 versus 13/31, p=0.000). Moreover, one case presented transient new spinal deficits after surgery, no permanent spinal deficit in group 1; 5 cases presented transient new spinal deficits, 2 cases showed permanent spinal deficit in group 2. And in group 2 the MEP amplitude before and after decompression had significant difference (134MUV+/-30.2 versus 65MUV+/-26.2, *p<0.05). CONCLUSION: Our results suggest that the IONM degenerations or postoperative spinal deficits are more likely to appear on patients with abnormal T2-WIs and T1-WIs. Appropriate and timely interventions are probably useful for IONM recovery. PMID- 28991690 TI - Neuromyelitis optica spectrum disorders with antibodies to myelin oligodendrocyte glycoprotein or aquaporin-4: Clinical and paraclinical characteristics in Algerian patients. AB - BACKGROUND: Neuromyelitis optica (NMO) is a severe autoimmune inflammatory disorder of the central nervous system. NMO and its abortive forms are referred to as NMO spectrum disorders (NMOSD). NMOSD are mostly associated with antibodies to aquaporin-4 (AQP4-IgG). However, recent studies have demonstrated antibodies to myelin oligodendrocyte glycoprotein (MOG-IgG) in a subset of patients. Data on NMOSD in North Africa are sparse. OBJECTIVE: To describe the frequency of MOG-IgG and AQP4-IgG among patients with optic neuritis (ON) and/or myelitis in Algeria as well as the clinical and paraclinical features associated with these antibodies. METHODS: Retrospective testing of 42 patients with optic neuritis and/or myelitis treated at the teaching hospital of TiziOuzou for MOG-IgG and AQP4-IgG, and retrospective evaluation of the patients' medical records. RESULTS: Six of 42 (14.3%) patients were positive for AQP4-IgG and 3/42 (7.1%) were positive for MOG-IgG. No patient was positive for both AQP4-IgG and MOG-IgG. All antibody-positive patients were women. MOG-IgG was associated with severe episodes of ON in all MOG-IgG-positive patients. Steroid treatment was followed by complete remission in two patients. AQP4-IgG was associated with ON and/or longitudinally extensive transverse myelitis (LETM), often with severe onset. While all six of the AQP4-IgG-positive patients met the 2015 IPND criteria for NMOSD, only one of the three MOG-IgG-positive patients did so. Interestingly, clinically silent extensive spinal cord or brain lesions were present in two of the three MOG-IgG-positive patients, and altered visual evoked potentials without clinical evidence of ON were found in three of the six AQP4-IgG-positive patients. CONCLUSION: MOG-IgG and AQP4-IgG are found in a substantial subset of Algerian patients with ON and/or myelitis, are present predominantly in women, and may be associated with differences in clinical presentation and, possibly, outcome. Only a subset of MOG-IgG positive patients meets the current diagnostic criteria for NMOSD. PMID- 28991691 TI - Management of hypertrophied dural lesions: Is surgery a better option? AB - It is often difficult to definitively diagnose dural lesions with hypertrophy as they exhibit nonspecific imaging findings and clinical symptoms. Most cases require histopathological evaluation with surgical intervention (such as biopsy). However, complications related to surgical interventions remain as matter of concern. Herein, we analyzed and verified the significance of surgery in 39 patients with hypertrophic dural lesions who were histopathologically diagnosed with surgical interventions. Specimens of dural lesions were obtained successfully, and it was possible to make a definitive diagnosis for each case based on histopathological findings. All patients tolerate the procedures well, and there were no evidences of surgery-related complications during surgical approach to the dura mater. Preoperative and pathological diagnoses varied in eight cases. Our results indicate that histopathological evaluation is important for distinguishing diseases showing dural hypertrophy even if surgical invasiveness is concerned. Neurosurgeons should not hesitate to perform surgery for management of dural lesions with hypertrophy in order to achieve accurate diagnosis. PMID- 28991692 TI - Altered expression of circular RNAs in Moyamoya disease. AB - Moyamoya disease (MMD) is the most common pediatric cerebrovascular disease in Eastern Asian countries but the etiology is not well understood. Circular RNAs (circRNAs) have been implicated in various biological processes, but their role in the development of MMD remains unclear. To address this issue, we carried out a comparative circRNA microarray analysis of blood samples obtained from patients with MMD and healthy subjects and identified 146 circRNAs that were differentially expressed between the two groups. Of these, 29 were upregulated and 117 were downregulated in patients as compared to controls (fold change >=2.0 and P<0.05). The microarray results were validated by quantitative reverse transcription PCR. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses revealed that the differentially expressed circRNAs were primarily involved in angiogenesis, metabolism, and immune responses in MMD. In addition, the mitogen-activated protein kinase signaling pathway was found to be the core regulatory pathway associated with disease pathogenesis. These results indicate that specific circRNAs are aberrantly expressed in MMD and are potential therapeutic targets for its treatment. PMID- 28991693 TI - Magnetic resonance and computed tomography image fusion technology in patients with Parkinson's disease after deep brain stimulation. AB - Electrode position after deep brain stimulation (DBS) for Parkinson's disease (PD) needs to be confirmed, but there are concerns about the risk of postoperative magnetic resonance imaging (MRI) after DBS. These issues could be avoided by fusion images obtained from preoperative MRI and postoperative computed tomography (CT). This study aimed to investigate image fusion technology for displaying the position of the electrodes compared with postoperative MRI. This was a retrospective study of 32 patients with PD treated with bilateral subthalamic nucleus (STN) DBS between April 2015 and March 2016. The postoperative (same day) CT and preoperative MRI were fused using the Elekta Leksell 10.1 planning workstation (Elekta Instruments, Stockholm, Sweden). The position of the electrodes was compared between the fusion images and postoperative 1-2-week MRI. The position of the electrodes was highly correlated between the fusion and postoperative MRI (all r between 0.865 and 0.996; all P<0.001). The differences of the left electrode position in the lateral and vertical planes was significantly different between the two methods (0.30 and 0.24mm, respectively, both P<0.05), but there were no significant differences for the other electrode and planes (all P>0.05). The position of the electrodes was highly correlated between the fusion and postoperative MRI. The CT-MRI fusion images could be used to avoid the potential risks of MRI after DBS in patients with PD. PMID- 28991694 TI - Dilemmas in the diagnosis and treatment of intracranial tuberculomas. AB - Tuberculosis (TB) remains a major public health problem across the globe. A common form of extrapulmonary TB (EPTB) with high mortality and morbidity is neuro TB or tuberculosis of the nervous system. The management of brain TB remains a big challenge due to the lack of specific diagnostic tools and appropriate treatment guidelines. In this context, this manuscript discusses clinical, diagnostic and treatment dilemmas in the management of intracranial tuberculomas. Brain tuberculoma may occur at any site within the cranium, no part of the brain substance or ventricular surface being exempt. The diagnosis of tuberculoma is often based on imaging techniques such as CT brain and MRI/MRS, even though, no radiological feature is confirmative or specific for tuberculoma. In this regard, a promising development is a new MRS marker that is currently being assessed. Based on a single peak at 3.8ppm, it may differentiate tuberculoma from tumors. This lack of diagnostic tools results in an increased cost to patient on average three times that for pulmonary TB. The increase in cost stems from multiple laboratory tests with diagnosis often achieved only after biopsy. As for treatment, the choice of drugs for treatment and the duration for treatment is also not clearly understood. The recent increase in drug resistant TB adds to the problem. The possible pitfalls during treatment include paradoxical response, hyponatremia, and development of hydrocephalus. These and other treatment related complications require follow-up and monitoring. A fraction of patients may even require emergency surgery due to increased intracranial tension. This can further increase cost to the patient and family. Overall, there is a need for continued efforts to develop new diagnostic tools for brain TB. Until such tools are available, high degree of awareness among treatment providers is necessary to avoid delays in diagnosis and increased costs. PMID- 28991695 TI - Monozygotic twins with a new compound heterozygous SPG11 mutation and different disease expression. AB - BACKGROUND: A pair of monozygotic 22-year-old twins with complicated hereditary spastic paraplegia caused by a novel SPG11 mutation is described. METHODS: Genetic testing and thorough clinical examination, magnetic resonance imaging (MRI) and MR-spectroscopy were performed. RESULTS: The twins were compound heterozygous for a known frameshift as well as a novel splice site mutation in the SPG11 gene. Clinically the patients showed a similar spectrum of symptoms but different disease presentation. MRI studies including morphometry and regional microstructural analysis by diffusion tensor imaging (DTI) of the corpus callosum (CC) by 3T MRI revealed marked thinning and corresponding increases of radial diffusivity (RD) and apparent diffusion coefficient (ADC) and reduction of the fractional anisotropy (FA) as compared to controls in all CC sections, particularly in the anterior callosal body. There was marked mainly supratentorial white matter reduction and to a lesser extent grey matter reduction in both patients. Involvement of the cortico-spinal tracts was reflected by FA and RD alterations. The more strongly affected patient showed a higher degree of callosal microstructural damage and cervical cord atrophy. CONCLUSIONS: This study shows a similar symptom spectrum, but distinct clinical and imaging findings in monozygotic twins suffering from SPG 11, suggesting individual downstream genetic effects and/or non-genetic modifiers. PMID- 28991696 TI - Aseptic meningitis due to reperfusion injury after carotid artery stenting. PMID- 28991697 TI - Zika virus disease-associated Guillain-Barre syndrome-Barranquilla, Colombia 2015 2016. AB - BACKGROUND: An outbreak of Guillain-Barre syndrome (GBS), a disorder characterized by acute, symmetric limb weakness with decreased or absent deep tendon reflexes, was reported in Barranquilla, Colombia, after the introduction of Zika virus in 2015. We reviewed clinical data for GBS cases in Barranquilla and performed a case-control investigation to assess the association of suspect and probable Zika virus disease with GBS. METHODS: We used the Brighton Collaboration Criteria to confirm reported GBS patients in Barranquilla during October 2015-April 2016. In April 2016, two neighborhood and age range-matched controls were selected for each confirmed GBS case-patient. We obtained demographics and antecedent symptoms in the 2-month period before GBS onset for case-patients and the same period for controls. Sera were collected for Zika virus antibody testing. Suspected Zika virus disease was defined as a history of rash and >=2 other Zika-related symptoms (fever, arthralgia, myalgia, or conjunctivitis). Probable Zika virus disease was defined as suspected Zika virus disease with laboratory evidence of a recent Zika virus or flavivirus infection. Conditional logistic regression adjusted for sex and race/ethnicity was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We confirmed 47 GBS cases. Incidence increased with age (10-fold higher in those >=60years versus those <20years). We interviewed 40 case-patients and 79 controls. There was no significant difference in laboratory evidence of recent Zika virus or flavivirus infection between case-patients and controls (OR: 2.2; 95% CI: 0.9-5.1). GBS was associated with having suspected (OR: 3.0, 95% CI: 1.1 8.6) or probable Zika virus disease (OR: 4.6, CI: 1.1-19.0). CONCLUSIONS: Older individuals and those with suspected and probable Zika virus disease had higher odds of developing GBS. KEY POINTS: We confirmed a Guillain-Barre syndrome (GBS) outbreak in Barranquilla, Colombia, during October 2015-April 2016. A case control investigation using neighborhood controls showed an association of suspected and probable Zika virus disease with GBS. PMID- 28991698 TI - PITX3 genotype and risk of dementia in Parkinson's disease: A population-based study. AB - Dementia is a devastating manifestation of Parkinson's disease (PD). This study investigates whether a common polymorphism in the PITX3 gene (rs2281983), which is of importance for the function of dopaminergic neurons, affects the risk of developing dementia in PD and whether it affects dopamine transporter (DAT) uptake. We PITX3 genotyped 133 patients with new-onset, idiopathic PD, participating in a population-based study in Sweden. Patients were followed prospectively during 6-11years with extensive investigations, including neuropsychology and DAT-imaging with 123I FP-CIT. The primary outcome was the incidence of PD dementia (PDD), diagnosed according to published criteria, studied by the Kaplan-Meier method and Cox proportional hazards. Performance in individual cognitive domains, the incidence of visual hallucinations, disease progression and striatal DAT uptake on imaging was also investigated. PD patients carrying the PITX3 C allele had an increased risk of developing PDD (hazard ratio: 2.87, 95% CI: 1.42-5.81, p=0.003), compared to the PD patients homozygous for the T-allele. Furthermore, the PITX3 C allele carriers with PD had a poorer cognitive performance in the visuospatial domain (p<0.001) and a higher incidence of visual hallucinations. A trend towards a lower striatal DAT uptake in the PITX3 C allele carriers was suggested, but could not be confirmed. Our results show that a common polymorphism in the PITX3 gene affects the risk of developing PDD and visuospatial dysfunction in idiopathic PD. If validated, these findings can provide new insights into the neurobiology and genetics of non-motor symptoms in PD. PMID- 28991699 TI - Microglial/macrophage markers CHI3L1, sCD14, and sCD163 in CSF and serum of pediatric inflammatory and non-inflammatory neurological disorders: A case control study and reference ranges. AB - OBJECTIVE: To assess the role of microglia and macrophages in neuroinflammatory disorders in children via biomarkers, and establish control reference ranges. METHODS: In an IRB-approved case-control study of 98 children, the concentrations of CSF/serum CHI3L1, sCD14, and sCD163 were measured by ELISA. Groups were controls (non-inflammatory neurological disorders, NIND, n=37), opsoclonus myoclonus syndrome (OMS, n=37), and other inflammatory neurological disorders (OIND, n=24). RESULTS: In control CSF, median concentrations (ng/ml) were 25 (IQR 16,41) for CHI3L1 and 42 (26,160) for sCD14; in serum, 16 (12,22) for CHI3L1, and 431 (270,957) for sCD163. The median CSF concentration of CHI3L1 in OIND was significantly higher than controls (2.9-fold, P<0.0001) and OMS (1.6-fold higher than controls, NS). The CSF sCD14 concentration was 1.9-fold higher in OIND (P=0.008) and 1.4-fold higher in OMS than controls. sCD163, below detection limits in CSF, was not significantly increased in OIND or OMS sera. CONCLUSIONS: CSF CHI3L1 and sCD14 elevations hold promise as immunomarkers in pediatric OIND, especially in high-expression individuals. These results provide evidence of innate immune system involvement in several pediatric neuroinflammatory disorders. Pediatric control data on CSF microglia/macrophage activation markers are hereby available for other investigators. PMID- 28991700 TI - Cardiac sympathetic denervation and dementia in de novo Parkinson's disease: A 7 year follow-up study. AB - BACKGROUND: Postganglionic cardiac sympathetic denervation is evident in patients with early-stage Parkinson's disease (PD). Cardiac iodine-123-meta iodobenzylguanidine (MIBG) uptake is correlated with the non-motor symptoms of PD, suggesting that low cardiac MIBG uptake may reflect wider alpha-synuclein pathology. In addition, low cardiac MIBG could be related to orthostatic hypotension in PD, which may affect cognition. However, the prognostic validity of baseline MIBG scintigraphy in terms of the risk of subsequent dementia remains unclear. We investigated whether cardiac MIBG uptake was associated with a later risk of dementia. METHODS: We retrospectively enrolled 93 drug-naive patients with de novo PD who underwent MIBG scanning on initial evaluation. The patients visited our outpatient clinic every 3-6months and were followed-up for a minimum of 4years from the time they were begun on dopaminergic medication. The predictive powers of baseline MIBG cardiac scintigraphic data in terms of dementia development were evaluated using Cox's proportional hazard models. RESULTS: During a mean follow-up period of 6.7years, 27 patients with PD (29.0%) developed dementia. These patients had less baseline MIBG uptake than did others (delayed H/M ratios: 1.19 vs. 1.31). Multivariate Cox's proportional hazard modeling revealed that both MIBG uptake (hazard ratio [HR] 3.40; p=0.004) and age (HR 1.08, p=0.01) significantly predicted dementia development. CONCLUSION: A reduction in cardiac MIBG uptake by PD patients may be associated with a subsequent risk of dementia; reduced uptake may reflect wider extension of alpha synuclein pathology in PD. PMID- 28991701 TI - Merkel cell carcinoma in a patient with relapsing-remitting multiple sclerosis treated with fingolimod. PMID- 28991702 TI - Cerebral autoregulation is preserved in multiple sclerosis patients. AB - Multiple sclerosis (MS) is an inflammatory disease that may also be associated with vascular dysfunction. One master component of vascular regulation is cerebral autoregulation (CA). We aimed to investigate the integrity of CA in MS patients and study its relationship with autonomic dysfunction (AD), magnetic resonance-imaging (MRI) lesion load and hemodynamic parameters. We enrolled 20 relapsing-remitting MS and 20 healthy subjects. CA was assessed by transfer function analysis parameters (coherence, gain and phase), as obtained in the very low, low and high-frequency domains (VLF, LF, HF, respectively). We evaluated the autonomic parameters heart rate variability and spontaneous baroreflex sensitivity (BRS). There were no significant differences in CA parameters between MS and controls (p>0.05). Lesion load was not correlated with any CA parameter. LF gain was positively correlated with BRS in both groups (MS: p=0.017; controls: p=0.025). Brainstem lesion load in MS was associated with higher systolic blood pressure (SBP; p=0.009). Our findings suggest that CA is preserved in our MS cohort. On the other hand, AD in MS patients with brainstem lesions could contribute to the increase of supine SBP. Whether this systemic deregulation could contribute to disease burden remains to be investigated. PMID- 28991703 TI - Klotho gene expression decreases in peripheral blood mononuclear cells (PBMCs) of patients with relapsing-remitting multiple sclerosis. AB - BACKGROUND: we recently showed that a hypothesized anti-aging and anti inflammatory protein, namely Klotho, may contribute to the etiology and/or pathogenesis of multiple sclerosis (MS). In addition, Klotho function and its gene expression are dependent on inflammatory pathways. Accordingly, the aim of this study was to investigate the Klotho gene expression within peripheral blood mononuclear cells (PBMCs) of patients with MS. METHODS: Altogether, 30 patients with relapsing-remitting MS (RRMS) along with 30 age and sex-matched healthy individuals were enrolled in this study. Blood samples were obtained from all participants and then PBMCs were isolated. The quantitative Real-Time PCR was carried out for Klotho mRNA derived from PBMCs. RESULTS: The results showed that klotho gene expression in the PBMCs of patients with RRMS is nearly 2.5-fold less than healthy individuals (P=0.0006). CONCLUSION: This is the first study demonstrating a possible role of Klotho in the PBMCs of MS patients. PMID- 28991704 TI - Neuroinflammation - A major cause for striatal dopaminergic degeneration in Parkinson's disease. AB - Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNPc). Growing evidence suggests that neuroinflammation plays a critical role in the pathogenesis of PD. Activation of proinflammatory pathways have a deleterious effect on dopaminergic neurons and are key factors contributing to the development of disease pathology. Clinical and preclinical evidence show microglial activation, infiltration of lymphocyte, elevated levels of pro inflammatory cytokines in various regions of the brain. In this review, we have discussed the possible mechanisms which are responsible for neuroinflammatoin and the therapeutic strategies to rescue dopaminergic neurons from these deleterious events. PMID- 28991705 TI - Primary glioblastoma multiforme of the conus medullaris with leptomeningeal metastasis. PMID- 28991706 TI - Apixaban for the treatment of cerebral venous thrombosis: A case series. AB - BACKGROUND: Venous thrombosis affecting cerebral veins and sinuses (CVT) is an uncommon neurological condition. Traditionally patients are treated with intravenous heparin followed by an oral vitamin K antagonist like warfarin. Direct oral anticoagulants (DOACs) may offer advantages over warfarin. There is evidence to demonstrate the effectiveness of both dabigatran and rivaroxaban. No data, however, has been published describing the use of apixaban in patients with CVT. METHODS: Report of three cases of CVT and review literature on available treatment options; efficacy and safety of novel oral anticoagulants in patients with systemic thrombosis. RESULTS: All patients presented with typical features of CVT. After confirming the diagnosis, they were acutely treated with heparin and later discharged on apixaban. During follow up visits, they tolerated apixaban well and did not have any bleeding complications. Follow up scans showed resolution of the thrombus and recanalization. CONCLUSION: CVT is an uncommon neurological condition and is often complicated by associated intraparenchymal hemorrhage. Although not recommended in current guidelines, apixaban may be a safe and effective option for the treatment of CVT. PMID- 28991707 TI - Tumefactive demyelinating lesions of 15 patients: Clinico-radiological features, management and review of the literature. AB - BACKGROUND AND OBJECTIVE: Tumefactive demyelinating lesions (TDLs) are large inflammatory lesions that can mimic tumors or other space-occupying lesions. Differential diagnosis and management of these lesions remain challenging for neurologists. We aim to review the clinico-radiological features of patients with TDLs, as well as their management. METHODS: We performed a retrospective review of cases of TDLs treated in our center from January 2010 to February 2017. We reviewed the literature. RESULTS: Out of 711 patients, we found 15 with TDLs (12 women and 3 men), with a mean age of TDL onset of 36years. Out of the 15 patients, 9 had TDLs as a first demyelinating event and 44% (4/15) of these converted to MS by McDonald 2010 criteria in a mean time of 8months (SD 3.10). Clinical presentation was polysymptomatic and the most common radiological findings included solitary lesions (66.66%), located primarily in the frontal (40%) or parietal (33%) lobes, showing mostly an infiltrative morphological pattern (50%) and an open-ring enhancement (43%). Multiple Sclerosis was the most common diagnosis (67%, 10/15). Acute treatment included steroids, plasmapheresis, rituximab and cyclophosphamide. CONCLUSIONS: Prevalence of tumefactive demyelination in MS was higher than expected in MS patients, according to literature. Time to conversion to MS was significantly shorter than other published series. Clinical presentation was polysymptomatic and the most common radiological findings were isolated frontal lesions with an open-ring enhancement. PMID- 28991708 TI - Post-cART progressive multifocal leukoencephalopathy era in a Brazilian center. AB - Progressive multifocal leukoencephalopathy (PML) is lytic infection of oligodendrocytes caused by JC virus (JCV). While PML incidence in developing countries has decreased after the introduction of combination antiretroviral therapy (cART), data in developing countries is scarce and limited to few cohorts. We described the epidemiological and clinical profile of a group of Brazilian HIV infected patients with PML in the cART era. A total of 27 patients were included in the study. The median age at PML onset was 42years (range: 27 67years) and 18 (66.7%) were men. The median CD4+ T cell count at the time of diagnosis was 67cells/mm3 and the median HIV viral load was 27,000copies/ml. Motor deficits were the most common early manifestations (44%). Seizures occurred in 37% of the patients and 9 (33.3%) had PML associated with immune reconstitution inflammatory syndrome (IRIS). Mortality was 33% and lower age at PML onset was associated with survival (p: 0.013). Our results are in accordance with previous published series of PML cases. Factors such as genetic background, regional JCV subtype differences, death from other diseases and underdiagnosis may explain the low prevalence of reported PML cases in developing countries. PMID- 28991709 TI - Five-year history of dysphagia as a sole initial symptom in inclusion body myositis. PMID- 28991710 TI - Yield of combined MRI sequences in isolated cortical vein thrombosis diagnosis. PMID- 28991711 TI - Tremor's glove-an innovative electrical muscle stimulation therapy for intractable tremor in Parkinson's disease: A randomized sham-controlled trial. AB - BACKGROUND: Medically refractory resting tremor is a debilitating symptom of Parkinson's disease (PD) patients. In our pilot study, modulation of peripheral reflex mechanism by electrical muscle stimulation (EMS) temporarily suppressed tremor. OBJECTIVES: To investigate the efficacy of EMS, delivered using Tremor's glove, as a treatment of resting hand tremor. PATIENTS AND METHODS: Thirty PD patients with medically refractory resting tremor were randomly allocated to a Tremor's glove group (n=15) or a sham glove group (n=15). Gloves were placed on the most tremulous hand for 30min per testing session. Demographics, clinical rating scales, and tremor parameters (RMS of angular velocity and angular displacement, peak magnitude, and frequency) were assessed before and during stimulation. Correlations with validated clinical rating scales were performed. RESULTS: There were no statistically significant differences between groups in demographics, rating scales, or tremor parameters. During stimulation, significant reduction in RMS angular velocity (as percentage) in every axis and peak magnitude in axis (x-, y-) and UPDRS tremor score, were found with Tremor's glove compared to the sham groups (p<0.05, each). Significant moderate correlations were observed between a percentage reduction of RMS angular velocity in every axis and UPDRS tremor scores. Mean duration of tremor reduction after stimulation was 107.78+/-104.15s. No serious adverse events were observed. CONCLUSION: In this study, EMS-based Tremor's glove was effective in suppressing resting hand tremor in PD patients. Tremor's glove is light-weight with a good safety profile, making it a future potential therapeutic option for PD patients with medically refractory tremor. PMID- 28991712 TI - Myasthenia gravis with systemic and neurological polyautoimmunity. PMID- 28991713 TI - Slowed abduction during smooth pursuit eye movement in episodic ataxia type 2 with a novel CACNA1A mutation. PMID- 28991714 TI - The pharmacological and non-pharmacological interventions for the management of fatigue related multiple sclerosis. AB - AIM: The clinical aim was to provide up-to-date evidence-based recommendations for the treatment of MS-related fatigue (MSRF). The scientific aim was to prioritise topics for future randomised clinical trials with sufficient power. METHODS: A systematic search of review based research that considered MSRF in adults (18years and over) was undertaken in May 2016. Data from reviews was extracted, critically appraised and synthesised using four specific techniques. RESULTS: A total of 24 reviews were identified (17 non-pharmacological, 5 pharmacological, 2 combining both), which contained 339 studies on interventions deigned to improve MSRF. The methodological quality of the reviews was identified by an average AMSTAR score of 6.5 (SD=1.87: 95% CI=5.75-7.25). No pharmacological intervention had strong evidence for improving MSRF. Limited/conflicting evidence was found for Amantadine and Prokarin and potential benefits for Modafinil were identified. Pemoline and Carnitine contained unclear/no evidence for fatigue management. Non-pharmacological interventions produced mixed conclusions regarding the effectiveness of the intervention to improve MSRF. Education (energy conservation and fatigue management) and exercise had supporting evidence for reducing MSRF but mixed conclusions gathered from subtypes of exercise. Reviews considering psycho-behavioural interventions (CBT and mindfulness) had limited information considering effectiveness. Finally, a single intervention combining physical and cognitive strategies showed more promising results. CONCLUSION: Further research into Pharmacological interventions for MSRF is required notably considering the potential of Modafinil. Yoga and energy conservation/fatigue management programs had strong evidence supporting use in management of MSRF. Due to the dissimilar interventions used in combined training the subtype of exercise cannot be recommended. Future research into Amantadine, psycho-behavioural interventions is vital to justify the current National Institute for Health and Care Excellence guidelines. The methodological quality of studies inhibited the ability of this review to provide other recommendations. PMID- 28991715 TI - Clinical and pathological findings in familial amyloid polyneuropathy caused by a transthyretin E61K mutation. AB - Familial amyloid polyneuropathy (FAP) is an autosomal dominant hereditary systemic amyloidosis caused by mutation of the transthyretin (TTR) gene, and usually shows sensory-dominant polyneuropathy and autonomic neuropathy at the initial stage. The pathogenesis of this neuropathy remains unknown, although several mechanisms, including mechanical compression, vessel occlusion, TTR toxicity and Schwann cell dysfunction have been proposed. We describe a patient with late-onset FAP caused by a TTR E61K mutation. Amyloid deposits were not detected in the endoneurium or perineurium of the sural nerve 7years after the onset of the disease, but a marked loss of nerve fibers was observed in the sural nerve. TTR-derived amyloid deposits were confirmed in the peroneus brevis muscle, salivary gland and heart tissue. DNA analysis revealed a heterozygous mutation in TTR. These findings suggest that proximal parts of the peripheral nervous system might be strongly affected by TTR aggregates or amyloid fibrils, and that the blood-nerve barrier in distal parts of peripheral nerves are initially preserved in this patient. This case indicates that several biopsy sites other than nerves may be helpful and necessary for the diagnosis of TTR amyloidosis in mild or late onset FAP. PMID- 28991716 TI - Utility of CISS sequence in detecting anteroinferior temporal encephalocele. PMID- 28991717 TI - New diagnostic criteria for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukocencephalopathy in Japan. AB - PURPOSE: Definite diagnosis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukocencephalopathy (CADASIL) is mostly done by identification of NOTCH3 mutations. We aimed to develop criteria for selecting patients suspected for CADASIL to undergo genetic testing. SUBJECTS AND METHODS: All subjects were Japanese. We recruited CADASIL patients genetically diagnosed up until 2011 (n=37, Group 1) or after 2011 (n=65, Group 2), 67 young stroke patients (<=55 years old), and 53 NOTCH3-negative CADASIL-like patients. The members of Japanese research committee for hereditary cerebral small vessel disease discussed and generated the new criteria to maximize positive rate in Group 1 CADASIL patients, followed by validation of sensitivity and specificity. RESULTS: In Group 1 CADASIL patients, the ages at onset excluding migraine were distributed widely (37-74 years old) and bimodal (<55 and >55 years old). Frequencies of an autosomal dominant family history and vascular risk factor(s) were 73 and 65%, respectively. From these findings, the panel considered appropriate cut-off values and weighting for each item. In CADASIL Group 1 versus young stroke controls, the sensitivity and specificity of the new criteria were 97.3% and 80.6%, respectively. However, in CADASIL Group 2 versus NOTCH3-negative controls, the sensitivity and specificity were 96.9% and 7.5%, respectively. Forty mutations of NOTCH3 distributed in exons 2-8, 11, 14, 18, 19, and 21 were identified in this study. Ten mutations were unreported ones. CONCLUSION: We propose the new criteria of high sensitivity, which will help physicians to assess the need for genetic testing. PMID- 28991719 TI - Neuroimaging and cognitive functions in temporal lobe epilepsy: A review of the literature. AB - Temporal lobe epilepsy (TLE) is the most common form of refractory focal epilepsy. Neuroimaging researches have demonstrated structural abnormalities in several cerebral regions. Cognitive impairment has been frequently described as a potential comorbidity of long-term TLE. This review investigated the state of research regarding neuropsychological impairment and neuroimaging studies in TLE patients. Studies were found on PubMed and Web of Sciences databases, 412 publications were selected: only 20 articles met search criteria. Results showed significant alterations in multiple cognitive domains, particularly memory, executive functions and language. The reported findings showed that the involvement of various factors, including neurobiological abnormalities and clinical features, is responsible for the onset of cognitive impairment in epileptic patients. PMID- 28991718 TI - Improving treatment times for patients with in-hospital stroke using a standardized protocol. AB - BACKGROUND: Previous reports have shown significant delays in treatment of in hospital stroke (IHS). We developed and implemented our IHS alert protocol in April 2014. We aimed to determine the influence of implementation of our IHS alert protocol. METHODS: Our implementation processes comprise the following four main steps: IHS protocol development, workshops for hospital staff to learn about the protocol, preparation of standardized IHS treatment kits, and obtaining feedback in a monthly hospital staff conference. We retrospectively compared protocol metrics and clinical outcomes of patients with IHS treated with intravenous thrombolysis and/or endovascular therapy between before (January 2008 March 2014) and after implementation (April 2014-December 2016). RESULTS: Fifty five patients were included (pre, 25; post, 30). After the implementation, significant reductions occurred in the median time from stroke recognition to evaluation by a neurologist (30 vs. 13.5min, p<0.01) and to first neuroimaging (50 vs. 26.5min, p<0.01) and in the median time from first neuroimaging to intravenous thrombolysis (45 vs. 16min, p=0.02). The median time from first neuroimaging to endovascular therapy had a tendency to decrease (75 vs. 53min, p=0.08). There were no differences in the favorable outcomes (modified Rankin scale score of 0-2) at discharge or the incidence of symptomatic intracranial hemorrhage between the two periods. CONCLUSION: Our IHS alert protocol implementation saved time in treating patients with IHS without compromising safety. PMID- 28991720 TI - Cerebral hyperperfusion syndrome and intracranial hemorrhage after carotid endarterectomy or carotid stenting: A meta-analysis. AB - INTRODUCTION: Cerebral hyperperfusion syndrome (CHS) and intracranial hemorrhage (ICH) after carotid revascularization have been associated with significant morbidity and mortality, although pooled data comparing these outcomes between open and endovascular treatment are lacking. Aim of this meta-analysis is to compare CHS and ICH risk between carotid endarterectomy (CEA) and carotid angioplasty with stenting (CAS). METHODS: A systematic literature review was conducted conforming to established criteria, in order to identify eligible articles published prior to February 2017. Eligible studies compared CHS and/or ICH between patients undergoing CEA and CAS. Other outcomes evaluated in this review included stroke and death due to ICH. Outcome risks are presented as odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Overall, 6 studies (5 studies reporting on CHS and 4 studies reporting on ICH) included 236,537 procedures (218,144 CEA; 18,393 CAS) in total. CEA was associated with a higher risk for CHS compared to CAS (pooled OR=1.432 [95% CI=1.078-1901]; P=0.015), although this difference was generated mainly from older studies (prior to 2012). However, no difference was found regarding ICH risk between the two methods (pooled OR=0.544 [95% CI=0.111-2.658]; P=0.452). Regarding stroke incidence, no difference was found between the two methods as well, although this resulted mainly from studies with a higher volume of CAS procedures (pooled OR=0.964 [95% CI=0.741-1.252]; P=0.833). Finally, death rate was significantly higher among patients with ICH compared to patients without ICH (pooled OR=386.977 [95% CI=246.746-606.906]; P<0.0001). Pooled data were not adequate to calculate potential risk factors for CHS/ICH after CEA compared to CAS. CONCLUSIONS: CEA seems to be associated with a higher risk for CHS compared to CAS, although this difference was generated mainly from older studies. However, there seems to be no difference regarding ICH risk between the two methods, with ICH being associated with a significantly higher risk for death. PMID- 28991722 TI - Risk of psychiatric disorders in Guillain-Barre syndrome: A nationwide, population-based, cohort study. AB - BACKGROUND: Guillain-Barre syndrome (GBS) is a rare immune-related neurological disorder with high mortality and morbidity, but the comorbid psychiatric disorders garnered little attention in the GBS patients. This study aimed to investigate the association between GBS and the risk of developing psychiatric disorders. METHODS: A total of 18,192 enrolled patients, with 4548 study subjects who had suffered GBS, and 13,644 controls matched for gender and age, from the Inpatient Dataset of 2000-2013 in Taiwan, and selected from the National Health Insurance Research Database (NHIRD). After adjusting for confounding factors, Cox proportional hazards analysis was used to compare the risk of developing psychiatric disorders during the 13years of follow-up. RESULTS: Of the study subjects, 471 (10.35%) developed psychiatric disorders when compared to 1023 (7.50%) in the control group. Fine and Gray's competing risk model analysis revealed that the study subjects were more likely to develop psychiatric disorders (crude hazard ratio [HR]: 4.281 (95% CI=3.819-4.798, p<0.001). After adjusting for gender, age, monthly income, urbanization level, geographic region, and comorbidities, the adjusted HR was 4.320 (95% CI=3.852-4.842, p<0.001). Dementia, depressive disorders, sleep disorders, and psychotic disorders predominate in these psychiatric disorders. Mechanical ventilation and hemodialysis are associated with a lower risk of dementia when compared to the control groups. CONCLUSIONS: Patients who suffered from GBS had a higher risk of developing psychiatric disorders, and this finding should act as a reminder to the clinicians that a regular psychiatric follow-up might well be needed for those patients. PMID- 28991721 TI - Clinical and imaging correlation in patients with pathologically confirmed tumefactive demyelinating lesions. AB - OBJECTIVES: To characterize clinical and imaging features in patients with pathologically confirmed demyelinating lesions. METHODS: In this retrospective chart review, we analyzed clinical-radiological-pathological correlations in patients >15years old who underwent brain biopsy at our institution between 2000 and 2015 and had inflammatory demyelination on neuropathology. RESULTS: Of 31 patients, the mean age was 42years (range 16 to 69years) and 55% were female. All but one of the biopsied lesions were considered tumefactive demyelinating lesions (TDLs) by imaging criteria, measuring >2cm on contrast-enhanced brain MRI. On clinical follow-up, the final diagnosis was a CNS malignancy in 2 patients (6.5%). In patients without malignant tumor, the TDL was solitary in 12 (41%) and multifocal in 17 (59%), with contrast enhancement in all but one case, primarily in an incomplete rim enhancement pattern (75.9%). Of 16 patients with at least 12months of clinical follow-up, 7 (43.8%) had a clinical relapse. Of patients without a prior neurologic history, relapse occurred in 2/7 (29%) in solitary TDL and 2/6 (33%) in multifocal lesions at initial presentation. Recurrent TDLs occurred in 3 patients, all with initially solitary TDLs. Stratifying by CSF analysis, 4 of 6 patients (67%) with either an elevated IgG Index or >2 oligoclonal bands suffered a clinical relapse compared to 2/8 (25%) with non inflammatory CSF. CONCLUSIONS: Pathologically confirmed TDLs call for careful clinical correlation, clinical follow-up and imaging surveillance. Although sometimes clinically monophasic, tumefactive demyelinating lesions carried nearly a 45% risk of near-term clinical relapse in our study, even when presenting initially as a solitary mass lesion. PMID- 28991723 TI - Infections and Chlamydia pneumoniae antibodies influence the functional outcome in thrombolysed strokes. AB - OBJECTIVE: Thrombolysis is effective in ischemic stroke patients, but some factors influence its benefit. Previous infections could increase the risk of ischemic stroke by an activation of systemic inflammation. We analysed the influence of previous infections and Chlamydia pneumoniae serology on functional outcome in thrombolysed stroke patients. METHODS: Consecutive thrombolysed stroke patients admitted during calendar year 2011 were analysed. Demographics, vascular risk factors, clinical and aetiological data were registered. Standardised blood tests were collected acutely for each patient, including inflammatory factors. Primary outcome was the functional outcome at 6months follow-up. t-test, Mann Withney U test and chi-square test were applied for univariate analysis, while a logistic regression was performed for multivariate analysis. RESULTS: A total of 142 patients were included in the analysis. Median onset-to-needle time was 156min. A previous infection occurred in 16.9% of patients, while a positive IgA antiChlamydia was detected in 40 cases. Good functional outcome was achieved by 72.5% of patients. At multivariate analysis poor outcome was associated to clinical severity, delay treatment time, haemorrhagic transformation and large artery etiological stroke type (p<0.01). Also IgA antiChlamydia pneumonia seropositivity (OR: 3.699; 95%CI: 1.094-12.512; p: 0.035) and poststroke infections (OR: 6.031; 95%CI: 2.485-11.301; p: 0.037) were predictors of poor outcome. INTERPRETATION: In this study IgA antiChlamydia pneumonia seropositivity represents a negative predictor of functional outcome in thrombolysed stroke patients. Further and larger studies are required to confirm these observations and to plan a prompt administration of antibiotics or immunomodulant agents. PMID- 28991724 TI - A Sparse Learning Framework for Joint Effect Analysis of Copy Number Variants. AB - Copy number variants (CNVs), including large deletions and duplications, represent an unbalanced change of DNA segments. Abundant in human genomes, CNVs contribute to a large proportion of human genetic diversity, with impact on many human phenotypes. Although recent advances in genetic studies have shed light on the impact of individual CNVs on different traits, the analysis of joint effect of multiple interactive CNVs lags behind from many perspectives. A primary reason is that the large number of CNV combinations and interactions in the human genome make it computationally challenging to perform such joint analysis. To address this challenge, we developed a novel sparse learning framework that combines sparse learning with biological networks to identify interacting CNVs with joint effect on particular traits. We showed that our approach performs well in identifying CNVs with joint phenotypic effect using simulated data. Applied to a real human genomic dataset from the 1,000 Genomes Project, our approach identified multiple CNVs that collectively contribute to population differentiation. We found a set of multiple CNVs that have joint effect in different populations, and affect gene expression differently in distinct populations. These results provided a collection of CNVs that likely have downstream biomedical implications in individuals from diverse population backgrounds. PMID- 28991725 TI - Learning Parameter-Advising Sets for Multiple Sequence Alignment. AB - While the multiple sequence alignment output by an aligner strongly depends on the parameter values used for the alignment scoring function (such as the choice of gap penalties and substitution scores), most users rely on the single default parameter setting provided by the aligner. A different parameter setting, however, might yield a much higher-quality alignment for the specific set of input sequences. The problem of picking a good choice of parameter values for specific input sequences is called parameter advising. A parameter advisor has two ingredients: (i) a set of parameter choices to select from, and (ii) an estimator that provides an estimate of the accuracy of the alignment computed by the aligner using a parameter choice. The parameter advisor picks the parameter choice from the set whose resulting alignment has highest estimated accuracy. In this paper, we consider for the first time the problem of learning the optimal set of parameter choices for a parameter advisor that uses a given accuracy estimator. The optimal set is one that maximizes the expected true accuracy of the resulting parameter advisor, averaged over a collection of training data. While we prove that learning an optimal set for an advisor is NP-complete, we show there is a natural approximation algorithm for this problem, and prove a tight bound on its approximation ratio. Experiments with an implementation of this approximation algorithm on biological benchmarks, using various accuracy estimators from the literature, show it finds sets for advisors that are surprisingly close to optimal. Furthermore, the resulting parameter advisors are significantly more accurate in practice than simply aligning with a single default parameter choice. PMID- 28991727 TI - A Time-Varying Nonparametric Methodology for Assessing Changes in QT Variability Unrelated to Heart Rate Variability. AB - OBJECTIVE: To propose and test a novel methodology to measure changes in QT interval variability (QTV) unrelated to RR interval variability (RRV) in nonstationary conditions. METHODS: Time-frequency coherent and residual spectra representing QTV related (QTVrRRV) and unrelated (QTVuRRV) to RRV, respectively, are estimated using time-frequency Cohen's class distributions. The proposed approach decomposes the nonstationary output spectrum of any two-input one-output model with uncorrelated inputs into two spectra representing the information related and unrelated to one of the two inputs, respectively. An algorithm to correct for the bias of the time-frequency coherence function between QTV and RRV is proposed to provide accurate estimates of both QTVuRRV and QTVrRRV. Two simulation studies were conducted to assess the methodology in challenging nonstationary conditions and data recorded during head-up tilt in 16 healthy volunteers were analyzed. RESULTS: In the simulation studies, QTVuRRV changes were tracked with only a minor delay due to the filtering necessary to estimate the nonstationary spectra. The correlation coefficient between theoretical and estimated patterns was even for extremely noisy recordings (signal to noise ratio (SNR) in QTV dB). During head-up tilt, QTVrRRV explained the largest proportion of QTV, whereas QTVuRRV showed higher relative increase than QTV or QTVrRRV in all spectral bands ( for most pairwise comparisons). CONCLUSION: The proposed approach accurately tracks changes in QTVuRRV. Head-up tilt induced a slightly greater increase in QTVuRRV than in QTVrRRV. SIGNIFICANCE: The proposed index QTVuRRV may represent an indirect measure of intrinsic ventricular repolarization variability, a marker of cardiac instability associated with sympathetic ventricular modulation and sudden cardiac death. PMID- 28991726 TI - Pathway Analysis with Signaling Hypergraphs. AB - Signaling pathways play an important role in the cell's response to its environment. Signaling pathways are often represented as directed graphs, which are not adequate for modeling reactions such as complex assembly and dissociation, combinatorial regulation, and protein activation/inactivation. More accurate representations such as directed hypergraphs remain underutilized. In this paper, we present an extension of a directed hypergraph that we call a signaling hypergraph. We formulate a problem that asks what proteins and interactions must be involved in order to stimulate a specific response downstream of a signaling pathway. We relate this problem to computing the shortest acyclic B-hyperpath in a signaling hypergraph-an NP-hard problem-and present a mixed integer linear program to solve it. We demonstrate that the shortest hyperpaths computed in signaling hypergraphs are far more informative than shortest paths, Steiner trees, and subnetworks containing many short paths found in corresponding graph representations. Our results illustrate the potential of signaling hypergraphs as an improved representation of signaling pathways and motivate the development of novel hypergraph algorithms. PMID- 28991728 TI - Screening for Cognitive Impairment by Model-Assisted Cerebral Blood Flow Estimation. AB - OBJECTIVE: Alzheimer's disease (AD) is a progressive and debilitating neurodegenerative disease; a major health concern in the ageing population with an estimated prevalence of 46 million dementia cases worldwide. Early diagnosis is therefore crucial so mitigating treatments can be initiated at an early stage. Cerebral hypoperfusion has been linked with blood-brain barrier dysfunction in the early stages of AD, and screening for chronic cerebral hypoperfusion in individuals has been proposed for improving the early diagnosis of AD. However, ambulatory measurements of cerebral blood flow are not routinely carried out in the clinical setting. In this study, we combine physiological modeling with Holter blood pressure monitoring and carotid ultrasound imaging to predict 24-h cerebral blood flow (CBF) profiles in individuals. One hundred and three participants [53 with mild cognitive impairment (MCI) and 50 healthy controls] underwent model-assisted prediction of 24-h CBF. Model-predicted CBF and neuropsychological tests were features in lasso regression models for MCI diagnosis. RESULTS: A CBF-enhanced classifier for diagnosing MCI performed better, area-under-the-curve (AUC) = 0.889 (95%-CI: 0.800 to 0.978), than a classifier based only on the neuropsychological test scores, AUC = 0.818 (95%-CI: 0.643 to 0.992). An additional cohort of 25 participants (11 MCI and 14 healthy) was recruited to perform model validation by arterial spin-labeling magnetic resonance imaging, and to establish a link between measured CBF that predicted by the model. CONCLUSION: Ultrasound imaging and ambulatory blood pressure measurements enhanced with physiological modeling can improve MCI diagnosis accuracy. PMID- 28991729 TI - Automatic Identification of Human Blastocyst Components via Texture. AB - Choosing the most viable embryo during human in vitro fertilization (IVF) is a prime factor in maximizing pregnancy rate. Embryologists visually inspect morphological structures of blastocysts under microscopes to gauge their health. Such grading introduces subjectivity amongst embryologists and adds to the difficulty of quality control during IVF. In this paper, we introduce an algorithm for automatic segmentation of two main components of human blastocysts named: Trophectoderm (TE) and inner cell mass (ICM). We utilize texture information along with biological and physical characteristics of day-5 human embryos (blastocysts) to identify TE or ICM regions according to their intrinsic properties. Both these regions are highly textured and very similar in the quality of their texture, and they often look connected to each other when imaged. These attributes make their automatic identification and separation from each other a difficult task even for an expert embryologist. By automatically identifying TE and ICM regions, we offer the opportunity to perform more detailed assessment of blastocysts. This could help in analyzing, in a quantitative way, various visual/geometrical characteristics of these regions that when combined with the pregnancy outcome can determine the predictive values of such attributes. Our work aids future research in understanding why certain embryos have higher pregnancy success rates. This paper is tested on a set of 211 blastocyst images. We report an accuracy of 86.6% for identification of TE and 91.3% for ICM. PMID- 28991731 TI - Automatic Temporal Segmentation of Vessels of the Brain Using 4D ASL MRA Images. AB - OBJECTIVE: Automatic vessel segmentation can be used to process the considerable amount of data generated by four-dimensional arterial spin labeling magnetic resonance angiography (4D ASL MRA) images. Previous segmentation approaches for dynamic series of images propose either reducing the series to a temporal average (tAIP) or maximum intensity projection (tMIP) prior to vessel segmentation, or a separate segmentation of each image. This paper introduces a method that combines both approaches to overcome the specific drawbacks of each technique. METHODS: Vessels in the tAIP are enhanced by using the ranking orientation responses of path operators and multiscale vesselness enhancement filters. Then, tAIP segmentation is performed using a seed-based algorithm. In parallel, this algorithm is also used to segment each frame of the series and identify small vessels, which might have been lost in the tAIP segmentation. The results of each individual time frame segmentation are fused using an or boolean operation. Finally, small vessels found only in the fused segmentation are added to the tAIP segmentation. RESULTS: In a quantitative analysis using ten 4D ASL MRA image series from healthy volunteers, the proposed combined approach reached an average Dice coefficient of 0.931, being more accurate than the corresponding tMIP, tAIP, and single time frame segmentation methods with statistical significance. CONCLUSION: The novel combined vessel segmentation strategy can be used to obtain improved vessel segmentation results from 4D ASL MRA and other dynamic series of images. SIGNIFICANCE: Improved vessel segmentation of 4D ASL MRA allows a fast and accurate assessment of cerebrovascular structures. PMID- 28991730 TI - Closed-Loop Vagus Nerve Stimulation Based on State Transition Models. AB - OBJECTIVE: Vagus nerve stimulation (VNS) is a potential therapeutic approach in a number of clinical applications. Although VNS is commonly delivered in an open loop approach, it is now recognized that closed-loop stimulation may be necessary to optimize the therapy. In this paper, we propose an original generic closed loop control system that can be readily integrated into an implantable device and allows for the adaptive modulation of multiple VNS parameters. METHODS: The proposed control method consists of a state transition model (STM), in which each state represents a set of VNS parameters, and a state transition algorithm that optimally selects the best STM state, minimizing the error between an observed physiological variable and a given target value. The proposed method has been integrated into a real-time adaptive VNS prototype system and has been applied here to the regulation of the instantaneous heart rate, working synchronously with cardiac cycles. A quantitative performance evaluation is performed on seven sheep by computing classical control performance indicators. A comparison with a proportional-integral (PI) controller is also performed. RESULTS: The STM controller presents a median mean square error, overshoot, and settling time, respectively, equal to 622.21 ms , 72.8%, and 7.5 beats. CONCLUSION: The proposed control method yields satisfactory accuracy and time response, while presenting a number of benefits over classical PI controllers. It represents a feasible approach for multiparametric VNS control on implantable devices. SIGNIFICANCE: Closed-loop multiparametric stimulation may improve response and minimize side effects on current pathologies treated by VNS. PMID- 28991732 TI - Feasibility of a Biomechanically-Assistive Garment to Reduce Low Back Loading During Leaning and Lifting. AB - GOAL: The purpose of this study was: 1) to design and fabricate a biomechanically assistive garment which was sufficiently lightweight and low-profile to be worn underneath, or as, clothing, and then 2) to perform human subject testing to assess the ability of the garment to offload the low back muscles during leaning and lifting. METHODS: We designed a prototype garment which acts in parallel with the low back extensor muscles to reduce forces borne by the lumbar musculature. We then tested eight healthy subjects while they performed common leaning and lifting tasks with and without the garment. We recorded muscle activity, body kinematics, and assistive forces. RESULTS: The biomechanically-assistive garment offloaded the low back muscles, reducing erector spinae muscle activity by an average of 23-43% during leaning tasks, and 14-16% during lifting tasks. CONCLUSION: Experimental findings in this study support the feasibility of using biomechanically-assistive garments to reduce low back muscle loading, which may help reduce injury risks or fatigue due to high or repetitive forces. SIGNIFICANCE: Biomechanically-assistive garments may have broad societal appeal as a lightweight, unobtrusive, and cost-effective means to mitigate low back loading in daily life. PMID- 28991733 TI - Isometric Non-Rigid Shape-from-Motion with Riemannian Geometry Solved in Linear Time. AB - We study Isometric Non-Rigid Shape-from-Motion (Iso-NRSfM): given multiple intrinsically calibrated monocular images, we want to reconstruct the time varying 3D shape of a thin-shell object undergoing isometric deformations. We show that Iso-NRSfM is solvable from local warps, the inter-image geometric transformations. We propose a new theoretical framework based on the Riemmanian manifold to represent the unknown 3D surfaces as embeddings of the camera's retinal plane. This allows us to use the manifold's metric tensor and Christoffel Symbol (CS) fields. These are expressed in terms of the first and second order derivatives of the inverse-depth of the 3D surfaces, which are the unknowns for Iso-NRSfM. We prove that the metric tensor and the CS are related across images by simple rules depending only on the warps. This forms a set of important theoretical results. We show that current solvers cannot solve for the first and second order derivatives of the inverse-depth simultaneously. We thus propose an iterative solution in two steps. 1) We solve for the first order derivatives assuming that the second order derivatives are known. We initialise the second order derivatives to zero, which is an infinitesimal planarity assumption. We derive a system of two cubics in two variables for each image pair. The sum-of squares of these polynomials is independent of the number of images and can be solved globally, forming a well-posed problem for $N?geq 3$ images. 2) We solve for the second order derivatives by initialising the first order derivatives from the previous step. We solve a linear system of $4N-4$ equations in three variables. We iterate until the first order derivatives converge. The solution for the first order derivatives gives the surfaces' normal fields which we integrate to recover the 3D surfaces. The proposed method outperforms existing work in terms of accuracy and computation cost on synthetic and real datasets. PMID- 28991734 TI - Characterization of Color Images with Multiscale Monogenic Maxima. AB - Can we build a feature-based analysis that fully characterizes images? The literature answers with edge-based reconstruction methods inspired by Marr's paradigm but limited to the greyscale case. This paper studies the color case. A new sparse representation is carried out with the monogenic concept and the Mallat-Zhong wavelet maxima method. Our monogenic maxima provide efficient contour shape and color characterization, as a sparse set of local features including amplitude, phase, orientation and ellipse parameters. This rich description takes the wavelet maxima representation further towards the wide topic of keypoint analysis. We propose a reconstruction process that retrieves the image from its monogenic maxima. While known works all rely on constrained optimization, implying an iterative use of the filterbank, we propose to interpolate the data in the feature domain by exploiting the visual knowledge from the feature-set. This direct retrieval is accurate enough so that no iteration is required. The main question is finally answered with comparative experiments. It is shown that a reasonably small amount of features is sufficiently informative for visually appealing image retrieval. The features appear numerically stable to rotation, and can be intuitively simplified to perform image regularization. PMID- 28991735 TI - ARIES: Enabling Visual Exploration and Organization of Art Image Collections. AB - Art historians have traditionally used physical light boxes to prepare exhibits or curate collections. On a light box, they can place slides or printed images, move the images around at will, group them as desired, and visual-ly compare them. The transition to digital images has rendered this workflow obsolete. Now, art historians lack well-designed, unified interactive software tools that effectively support the operations they perform with physi-cal light boxes. To address this problem, we designed ARIES (ARt Image Exploration Space), an interactive image manipulation system that enables the exploration and organization of fine digital art. The system allows images to be compared in multiple ways, offering dynamic overlays analogous to a physical light box, and sup-porting advanced image comparisons and feature-matching functions, available through computational image processing. We demonstrate the effectiveness of our system to support art historians tasks through real use cases. PMID- 28991736 TI - Quasi-Random Single-Point Imaging Using Low-Discrepancy $k$ -Space Sampling. AB - Magnetic resonance imaging of short relaxation time spin systems has been a widely discussed topic with serious clinical applications and led to the emergence of fast imaging ultra-short echo-time sequences. Nevertheless, these sequences suffer from image blurring, due to the related sampling point spread function and are highly prone to imaging artefacts arising from, e.g., chemical shifts or magnetic susceptibilities. In this paper, we present a concept of spherical quasi-random single-point imaging. The approach is highly accelerateable, due to intrinsic undersampling properties and capable of strong metal artefact suppression. Imaging acceleration is achieved by sampling of quasi random points in -space, based on a low-discrepancy sequence, and a combination with non-linear optimization reconstruction techniques [compressed sensing (CS)]. The presented low-discrepancy trajectory shows ideal noise like undersampling properties for the combination with CS, leading to denoised images with excellent metal artefact reduction. Using eightfold undersampling, acquisition time of a few minutes can be achieved for volume acquisitions. PMID- 28991737 TI - Exact Calculation of Noise Maps and ${g}$ -Factor in GRAPPA Using a ${k}$ -Space Analysis. AB - Characterization of the noise distribution in magnetic resonance images has multiple applications, including quality assurance and protocol optimization. Noise characterization is particularly important in the presence of parallel imaging acceleration with multi-coil acquisitions, where the noise distribution can contain severe spatial heterogeneities. If the parallel imaging reconstruction is a linear process, an accurate noise analysis can be carried out by taking into account the correlations between all the samples involved. However, for -space-based techniques such as generalized autocalibrating partially parallel acquisition (GRAPPA), the exact analysis has been considered computationally prohibitive due to the very large size of the noise covariance matrices required to characterize the noise propagation from -space to image space. Previously proposed methods avoid this computational burden by formulating the GRAPPA reconstruction as a pixel-wise linear operation performed in the image space. However, these methods are not exact in the presence of non-uniform sampling of -space (e.g., containing a calibration region). For this reason, in this paper, we develop an accurate characterization of the noise distribution for self-calibrated parallel imaging in the presence of arbitrary Cartesian sampling patterns. By exploiting the symmetries and separability in the noise propagation process, the proposed method is computationally efficient and does not require large matrices. Under the assumption of a fixed reconstruction kernel, this method provides the precise distribution of the noise variance for each coil's image. These coil-by-coil noise maps are subsequently combined according to the coil combination approach used in image reconstruction, and therefore can be applied with both complex coil combination and root-sum-of-squares approaches. In this paper, we present the proposed noise characterization method and compare it to previous techniques using Monte Carlo simulations as well as phantom acquisitions. PMID- 28991738 TI - FoCUS: Fourier-Based Coded Ultrasound. AB - Modern imaging systems typically use single-carrier short pulses for transducer excitation. Coded signals together with pulse compression are successfully used in radar and communication to increase the amount of transmitted energy. Previous research verified significant improvement in signal-to-noise ratio (SNR) and imaging depth for ultrasound imaging with coded signals. Since pulse compression needs to be applied at each transducer element, the implementation of coded excitation (CE) in array imaging is computationally complex. Applying pulse compression on the beamformer output reduces the computational load but degrades both the axial and lateral point spread function, compromising image quality. In this paper, we present an approach for efficient implementation of pulse compression by integrating it into frequency domain beamforming. This method leads to significant reduction in the amount of computations without affecting axial resolution. The lateral resolution is dictated by the factor of savings in computational load. We verify the performance of our method on a Verasonics imaging system and compare the resulting images to time-domain processing. The computational savings are evaluated for a minimal sampling rate of four times the central frequency. We show that from 4- to 33-fold reduction is achieved as a function of the resulting lateral resolution, with no degradation of axial resolution. For an imaging system operating at a higher sampling rate, e.g., 10 times the central frequency, the savings can be as high as 77-fold. The efficient implementation makes CE a feasible approach in array imaging with the potential to enhance SNR as well as improve imaging depth and frame rate. PMID- 28991739 TI - Online Low-Rank Representation Learning for Joint Multi-Subspace Recovery and Clustering. AB - Benefiting from global rank constraints, the low-rank representation (LRR) method has been shown to be an effective solution to subspace learning. However, the global mechanism also means that the LRR model is not suitable for handling large scale data or dynamic data. For large-scale data, the LRR method suffers from high time complexity, and for dynamic data, it has to recompute a complex rank minimization for the entire data set whenever new samples are dynamically added, making it prohibitively expensive. Existing attempts to online LRR either take a stochastic approach or build the representation purely based on a small sample set and treat new input as out-of-sample data. The former often requires multiple runs for good performance and thus takes longer time to run, and the latter formulates online LRR as an out-of-sample classification problem and is less robust to noise. In this paper, a novel online LRR subspace learning method is proposed for both large-scale and dynamic data. The proposed algorithm is composed of two stages: static learning and dynamic updating. In the first stage, the subspace structure is learned from a small number of data samples. In the second stage, the intrinsic principal components of the entire data set are computed incrementally by utilizing the learned subspace structure, and the LRR matrix can also be incrementally solved by an efficient online singular value decomposition algorithm. The time complexity is reduced dramatically for large scale data, and repeated computation is avoided for dynamic problems. We further perform theoretical analysis comparing the proposed online algorithm with the batch LRR method. Finally, experimental results on typical tasks of subspace recovery and subspace clustering show that the proposed algorithm performs comparably or better than batch methods, including the batch LRR, and significantly outperforms state-of-the-art online methods. PMID- 28991740 TI - Duplex Metric Learning for Image Set Classification. AB - Image set classification has attracted much attention because of its broad applications. Despite the success made so far, the problems of intra-class diversity and inter-class similarity still remain two major challenges. To explore a possible solution to these challenges, this paper proposes a novel approach, termed duplex metric learning (DML), for image set classification. The proposed DML consists of two progressive metric learning stages with different objectives used for feature learning and image classification, respectively. The metric learning regularization is not only used to learn powerful feature representations but also well explored to train an effective classifier. At the first stage, we first train a discriminative stacked autoencoder (DSAE) by layer wisely imposing a metric learning regularization term on the neurons in the hidden layers and meanwhile minimizing the reconstruction error to obtain new feature mappings in which similar samples are mapped closely to each other and dissimilar samples are mapped farther apart. At the second stage, we discriminatively train a classifier and simultaneously fine-tune the DSAE by optimizing a new objective function, which consists of a classification error term and a metric learning regularization term. Finally, two simple voting strategies are devised for image set classification based on the learnt classifier. In the experiments, we extensively evaluate the proposed framework for the tasks of face recognition, object recognition, and face verification on several commonly-used data sets and state-of-the-art results are achieved in comparison with existing methods. PMID- 28991741 TI - Variational Decompression of Image Data From DjVu Encoded Files. AB - The DjVu file format and image compression techniques are widely used in the archival of digital documents. Its key ingredients are the separation of the document into fore- and background layers and a binary switching mask, followed by a lossy, transform-based compression of the former and a dictionary-based compression of the latter. The lossy compression of the layers is based on a wavelet decomposition and bit truncation, which leads, in particular at higher compression rates, to severe compression artifacts in the standard decompression of the layers. The aim of this paper is to break ground for the variational decompression of DjVu files. To this aim, we provide an in-depth analysis and discussion of the compression standard with a particular focus on modeling data constraints for decompression. This allows to carry out DjVu decompression as regularized inversion of the compression procedure. As particular example, we evaluate the performance of such a framework using total variation and total generalized variation regularization. Furthermore, we provide routines for obtaining the necessary data constraints from a compressed DjVu file and for the forward and adjoint transformation operator involved in DjVu compression. PMID- 28991742 TI - A Physics-Based Deep Learning Approach to Shadow Invariant Representations of Hyperspectral Images. AB - This paper proposes the Relit Spectral Angle-Stacked Autoencoder, a novel unsupervised feature learning approach for mapping pixel reflectances to illumination invariant encodings. This work extends the Spectral Angle-Stacked Autoencoder so that it can learn a shadow-invariant mapping. The method is inspired by a deep learning technique, Denoising Autoencoders, with the incorporation of a physics-based model for illumination such that the algorithm learns a shadow invariant mapping without the need for any labelled training data, additional sensors, a priori knowledge of the scene or the assumption of Planckian illumination. The method is evaluated using datasets captured from several different cameras, with experiments to demonstrate the illumination invariance of the features and how they can be used practically to improve the performance of high-level perception algorithms that operate on images acquired outdoors. PMID- 28991743 TI - Curvature Integration in a 5D Kernel for Extracting Vessel Connections in Retinal Images. AB - Tree-like structures, such as retinal images, are widely studied in computer aided diagnosis systems for large-scale screening programs. Despite several segmentation and tracking methods proposed in the literature, there still exist several limitations specifically when two or more curvilinear structures cross or bifurcate, or in the presence of interrupted lines or highly curved blood vessels. In this paper, we propose a novel approach based on multi-orientation scores augmented with a contextual affinity matrix, which both are inspired by the geometry of the primary visual cortex (V1) and their contextual connections. The connectivity is described with a 5D kernel obtained as the fundamental solution of the Fokker-Planck equation modeling the cortical connectivity in the lifted space of positions, orientations, curvatures, and intensity. It is further used in a self-tuning spectral clustering step to identify the main perceptual units in the stimuli. The proposed method has been validated on several easy as well as challenging structures in a set of artificial images and actual retinal patches. Supported by quantitative and qualitative results, the method is capable of overcoming the limitations of current state-of-the-art techniques. PMID- 28991744 TI - Convolutional Dictionary Learning: Acceleration and Convergence. AB - Convolutional dictionary learning (CDL or sparsifying CDL) has many applications in image processing and computer vision. There has been growing interest in developing efficient algorithms for CDL, mostly relying on the augmented Lagrangian (AL) method or the variant alternating direction method of multipliers (ADMM). When their parameters are properly tuned, AL methods have shown fast convergence in CDL. However, the parameter tuning process is not trivial due to its data dependence and, in practice, the convergence of AL methods depends on the AL parameters for nonconvex CDL problems. To moderate these problems, this paper proposes a new practically feasible and convergent Block Proximal Gradient method using a Majorizer (BPG-M) for CDL. The BPG-M-based CDL is investigated with different block updating schemes and majorization matrix designs, and further accelerated by incorporating some momentum coefficient formulas and restarting techniques. All of the methods investigated incorporate a boundary artifacts removal (or, more generally, sampling) operator in the learning model. Numerical experiments show that, without needing any parameter tuning process, the proposed BPG-M approach converges more stably to desirable solutions of lower objective values than the existing state-of-the-art ADMM algorithm and its memory efficient variant do. Compared with the ADMM approaches, the BPG-M method using a multi-block updating scheme is particularly useful in single-threaded CDL algorithm handling large data sets, due to its lower memory requirement and no polynomial computational complexity. Image denoising experiments show that, for relatively strong additive white Gaussian noise, the filters learned by BPG-M based CDL outperform those trained by the ADMM approach. PMID- 28991745 TI - Multiple-Level Feature-Based Measure for Retargeted Image Quality. AB - Objective image retargeting quality assessment aims to use computational models to predict the retargeted image quality consistent with subjective perception. In this paper, we propose a multiple-level feature (MLF)-based quality measure to predict the perceptual quality of retargeted images. We first provide an in-depth analysis on the low-level aspect ratio similarity feature, and then propose a mid level edge group similarity feature, to better address the shape/structure related distortion. Furthermore, a high-level face block similarity feature is designed to deal with sensitive region deformation. The multiple-level features are complementary as they quantify different aspects of quality degradation in the retargeted image, and the MLF measure learned by regression is used to predict the perceptual quality of retargeted images. Extensive experimental results performed on two public benchmark databases demonstrate that the proposed MLF measure achieves higher quality prediction accuracy than the existing relevant state-of-the-art quality measures. PMID- 28991746 TI - Compensation for Magnetic Disturbances in Motion Estimation to Provide Feedback to Wearable Robotic Systems. AB - The direction of the Earth's magnetic field is used as a reference vector to determine the heading in orientation estimation with wearable sensors. However, the magnetic field strength is weak and can be easily disturbed in the vicinity of ferromagnetic materials, which may result in inaccurate estimate of orientation. This paper presents a novel method for estimating and compensating for magnetic disturbances. The compensation algorithm is implemented within a kinematic-based extended Kalman filter and is based on an assessment of the magnetic disturbance and the change of orientation in each time step. The proposed algorithm was experimentally validated by measuring the orientation of a simple mechanical system with three degrees of freedom in an artificially disturbed magnetic field. The results of the experimental evaluation show that an Kalman filter algorithm that incorporates compensating for magnetic disturbances is capable of estimating the orientation with moderate error (the absolute median errors , ) when the Earth's magnetic field is disturbed by magnetic disturbance with a magnitude equal to twice the magnitude of the Earth's own magnetic field in different directions. PMID- 28991747 TI - DNA Implementation of Fuzzy Inference Engine: Towards DNA Decision-Making Systems. AB - Decision-making systems are an integral part of any autonomous device. With the recent developments in bio-nanorobots, smart drugs, and engineered viruses, there is an immediate need of decision-making systems which are bio-compatible in nature. DNA is considered a perfect candidate for designing the computing systems in such decision-making systems because of their bio-compatibility and programmability. Complex biological systems can be easily modeled/controlled using fuzzy logic operations with the help of linguistic rules. In this paper, we propose an enzyme-free DNA strand displacement-based architecture of fuzzy inference engine using the fuzzy operators, such as fuzzy intersection and union. The basic building blocks of this architecture are minimum, maximum, and fan-out gates. All these gates are analog in nature, which means that the input/output values of the gates are represented by the concentration of the input/output DNA strands. To demonstrate the performance of the proposed architecture, a detailed design, analysis, and kinetic simulation of each gate were carried out. Finally, the minimum and maximum gates are cascaded according to the pre-defined rules to design the fuzzy inference engine. All these DNA circuits are implemented and simulated in Visual DSD software. PMID- 28991748 TI - Cell Population Tracking in a Honeycomb Structure Using an IMM Filter Based 3D Local Graph Matching Model. AB - Developing algorithms for plant cell population tracking is very critical for the modeling of plant cell growth pattern and gene expression dynamics. The tracking of plant cells in microscopic image stacks is very challenging for several reasons: (1) plant cells are densely packed in a specific honeycomb structure; (2) they are frequently dividing; and (3) they are imaged in different layers within 3D image stacks. Based on an existing 2D local graph matching algorithm, this paper focuses on building a 3D plant cell matching model, by exploiting the cells' 3D spatiotemporal context. Furthermore, the Interacting Multi-Model filter (IMM) is combined with the 3D local graph matching model to track the plant cell population simultaneously. Because our tracking algorithm does not require the identification of "tracking seeds", the tracking stability and efficiency are greatly enhanced. Last, the plant cell lineages are achieved by associating the cell tracklets, using a maximum-a-posteriori (MAP) method. Compared with the 2D matching method, the experimental results on multiple datasets show that our proposed approach does not only greatly improve the tracking accuracy by 18 percent, but also successfully tracks the plant cells located at the high curvature primordial region, which is not addressed in previous work. PMID- 28991749 TI - Novel Consensus Gene Selection Criteria for Distributed GPU Partial Least Squares based Gene Microarray Analysis in Diffused Large B Cell Lymphoma (DLBCL) and related findings. AB - This paper proposes novel consensus gene selection criteria for partial least squares-based gene microarray analysis. By quantifying the extent of consistency and distinctiveness of the differential gene expressions across different double cross validations (CV) or randomizations in terms of occurrence and randomization p-values, the proposed criteria are able to identify a more comprehensive genes associated with the underlying disease. A Distributed GPU implementation has been proposed to accelerate the gene selection problem and about 8-11 times speed up has been achieved based on the microarray datasets considered. Simulation results using various cancer gene microarray datasets show that the proposed approach is able to achieve highly comparable classification accuracy in comparing with many conventional approaches. Furthermore, enrichment analysis on the selected genes for Diffused Large B Cell Lymphoma (DLBCL) and Prostate Cancer datasets and show that only the proposed approach is able to identify gene lists enriched in different pathways with significant p-values. In contrast, sufficient statistical significance cannot be found for conventional SVM-RFE and the t-test. The reliability in identifying and establishing statistical significance of the gene findings makes the proposed approach an attractive alternative for cancer related researches based on gene expression profiling or other similar data. PMID- 28991750 TI - Kmerind: A Flexible Parallel Library for K-mer Indexing of Biological Sequences on Distributed Memory Systems. AB - Counting and indexing fixed length substrings, or k-mers, in biological sequences is a key step in many bioinformatics tasks including genome alignment and mapping, genome assembly, and error correction. While advances in next generation sequencing technologies have dramatically reduced the cost and improved latency and throughput, few bioinformatics tools can efficiently process the datasets at the current generation rate of 1.8 terabases every 3 days. We present Kmerind, a high performance parallel k-mer indexing library for distributed memory environments. The Kmerind library provides a set of simple and consistent APIs with sequential semantics and parallel implementations that are designed to be flexible and extensible. Kmerind's k-mer counter performs similarly or better than the best existing k-mer counting tools even on shared memory systems. In a distributed memory environment, Kmerind counts k-mers in a 120 GB sequence read dataset in less than 13 seconds on 1024 Xeon CPU cores, and fully indexes their positions in approximately 17 seconds. Querying for 1% of the k-mers in these indices can be completed in 0.23 seconds and 28 seconds, respectively. Kmerind is the first k-mer indexing library for distributed memory environments, and the first extensible library for general k-mer indexing and counting. Kmerind is available at https://github.com/ParBLiSS/kmerind. PMID- 28991751 TI - Unified Deep Learning Architecture for Modeling Biology Sequence. AB - Prediction of the spatial structure or function of biological macromolecules based on their sequences remains an important challenge in bioinformatics. When modeling biological sequences using traditional sequencing models, long-range interaction, complicated and variable output of labeled structures, and variable length of biological sequences usually lead to different solutions on a case-by case basis. This study proposed a unified deep learning architecture based on long short-term memory or a gated recurrent unit to capture long-range interactions. The architecture designs the optional reshape operator to adapt to the diversity of the output labels and implements a training algorithm to support the training of sequence models capable of processing variable-length sequences. The merging and pooling operators enhances the ability of capturing short-range interactions between basic units of biological sequences. The proposed deep learning architecture and its training algorithm might be capable of solving currently variable biological sequence-modeling problems under a unified framework. We validated the model on one of the most difficult biological sequence-modeling problems, protein residue interaction prediction. The results indicate that the accuracy of obtaining the residue interactions of the model exceeded popular approaches by 10 percent on multiple widely-used benchmarks. PMID- 28991752 TI - Linear time algorithms to construct populations fitting multiple constraint distributions at genomic scales. AB - Computer simulations can be used to study population genetic methods, models and parameters, as well as to predict potential outcomes. For example, in plant populations, predicting the outcome of breeding operations can be studied using simulations. In-silico construction of populations with pre-specified characteristics is an important task in breeding optimization and other population genetic studies. We present two linear time Simulation using Best-fit Algorithms (SimBA) for two classes of problems where each co-fits two distributions: SimBA-LD fits linkage disequilibrium and minimum allele frequency distributions, while SimBA-hap fits founder-haplotype and polyploid allele dosage distributions. An incremental gap-filling version of previously introduced SimBA LD is here demonstrated to accurately fit the target distributions, allowing efficient large scale simulations. SimBA-hap accuracy and efficiency is demonstrated by simulating tetraploid populations with varying numbers of founder haplotypes, we evaluate both a linear time greedy algoritm and an optimal solution based on mixed-integer programming. SimBA is available on http://researcher.watson.ibm.com/project/5669. PMID- 28991753 TI - A Survey on Computer Vision for Assistive Medical Diagnosis From Faces. AB - Automatic medical diagnosis is an emerging center of interest in computer vision as it provides unobtrusive objective information on a patient's condition. The face, as a mirror of health status, can reveal symptomatic indications of specific diseases. Thus, the detection of facial abnormalities or atypical features is at upmost importance when it comes to medical diagnostics. This survey aims to give an overview of the recent developments in medical diagnostics from facial images based on computer vision methods. Various approaches have been considered to assess facial symptoms and to eventually provide further help to the practitioners. However, the developed tools are still seldom used in clinical practice, since their reliability is still a concern due to the lack of clinical validation of the methodologies and their inadequate applicability. Nonetheless, efforts are being made to provide robust solutions suitable for healthcare environments, by dealing with practical issues such as real-time assessment or patients positioning. This survey provides an updated collection of the most relevant and innovative solutions in facial images analysis. The findings show that with the help of computer vision methods, over 30 medical conditions can be preliminarily diagnosed from the automatic detection of some of their symptoms. Furthermore, future perspectives, such as the need for interdisciplinary collaboration and collecting publicly available databases, are highlighted. PMID- 28991754 TI - Temporal Analysis of Cardiovascular and Respiratory Complexity by Multiscale Entropy Based on Symbolic Dynamics. AB - The effect of an orthostatic stress on cardiovascular and respiratory complexity was investigated to detect impaired autonomic regulation in patients with vasovagal syncope (VVS). A total of 16 female patients and 12 age-matched healthy female subjects were enrolled in a passive 70 degrees head-up tilt test. Also, 12 age-matched healthy male subjects were enrolled to study gender differences. Analysis was performed dynamically using various short-term (5 min) windows shifted by 1 min as well as by 20 min of orthostatic phase (OP) to evaluate local and global complexity. Complexity was determined over multiple time scales by the established method of refined composite multiscale entropy (RCMSE) and by a new proposed method of multiscale entropy based on symbolic dynamics (MSE-SD). Concerning heart rate variability (HRV) during OP, both methods revealed the highest complexity for female controls followed by lower complexity in male controls (p < 0.01) and by the lowest complexity in female patients (p < 0.01). For blood pressure variability (BPV), no gender differences in controls were shown by any method. However, MSE-SD demonstrated highly significantly increased BPV complexity in patients during OP (p < 0.01 on 4 time-scales after 7 min, p < 0.001 on 5 time-scales after 11 min) while RCMSE did not reveal considerable differences (p < 0.05 on 2 time scales after 7 min). Respiratory complexity was further increased in patients primary shown by MSE-SD. Findings indicated impaired autonomic regulation in VVS patients characterized by predominantly increased BPV complexity accompanied with decreased HRV complexity. In addition, results suggested extending the concept of complexity loss with disease. PMID- 28991755 TI - Robust Discriminant Regression for Feature Extraction. AB - Ridge regression (RR) and its extended versions are widely used as an effective feature extraction method in pattern recognition. However, the RR-based methods are sensitive to the variations of data and can learn only limited number of projections for feature extraction and recognition. To address these problems, we propose a new method called robust discriminant regression (RDR) for feature extraction. In order to enhance the robustness, the L2,1-norm is used as the basic metric in the proposed RDR. The designed robust objective function in regression form can be solved by an iterative algorithm containing an eigenfunction, through which the optimal orthogonal projections of RDR can be obtained by eigen decomposition. The convergence analysis and computational complexity are presented. In addition, we also explore the intrinsic connections and differences between the RDR and some previous methods. Experiments on some well-known databases show that RDR is superior to the classical and very recent proposed methods reported in the literature, no matter the L2-norm or the L2,1 norm-based regression methods. The code of this paper can be downloaded from http://www.scholat.com/laizhihui. PMID- 28991756 TI - Person Reidentification via Discrepancy Matrix and Matrix Metric. AB - Person reidentification (re-id), as an important task in video surveillance and forensics applications, has been widely studied. Previous research efforts toward solving the person re-id problem have primarily focused on constructing robust vector description by exploiting appearance's characteristic, or learning discriminative distance metric by labeled vectors. Based on the cognition and identification process of human, we propose a new pattern, which transforms the feature description from characteristic vector to discrepancy matrix. In particular, in order to well identify a person, it converts the distance metric from vector metric to matrix metric, which consists of the intradiscrepancy projection and interdiscrepancy projection parts. We introduce a consistent term and a discriminative term to form the objective function. To solve it efficiently, we utilize a simple gradient-descent method under the alternating optimization process with respect to the two projections. Experimental results on public datasets demonstrate the effectiveness of the proposed pattern as compared with the state-of-the-art approaches. PMID- 28991757 TI - An Adaptive Primal-Dual Subgradient Algorithm for Online Distributed Constrained Optimization. AB - In this paper, we consider the problem of solving distributed constrained optimization over a multiagent network that consists of multiple interacting nodes in online setting, where the objective functions of nodes are time-varying and the constraint set is characterized by an inequality. Through introducing a regularized convex-concave function, we present a consensus-based adaptive primal dual subgradient algorithm that removes the need for knowing the total number of iterations in advance. We show that the proposed algorithm attains an [where ] regret bound and an bound on the violation of constraints; in addition, we show an improvement to an regret bound when the objective functions are strongly convex. The proposed algorithm allows a novel tradeoffs between the regret and the violation of constraints. Finally, a numerical example is provided to illustrate the effectiveness of the algorithm. PMID- 28991758 TI - Adaptive Gradient Multiobjective Particle Swarm Optimization. AB - An adaptive gradient multiobjective particle swarm optimization (AGMOPSO) algorithm, based on a multiobjective gradient (stocktickerMOG) method and a self adaptive flight parameters mechanism, is developed to improve the computation performance in this paper. In this AGMOPSO algorithm, the stocktickerMOG method is devised to update the archive to improve the convergence speed and the local exploitation in the evolutionary process. Meanwhile, the self-adaptive flight parameters mechanism, according to the diversity information of the particles, is then established to balance the convergence and diversity of AGMOPSO. Attributed to the stocktickerMOG method and the self-adaptive flight parameters mechanism, this AGMOPSO algorithm not only has faster convergence speed and higher accuracy, but also its solutions have better diversity. Additionally, the convergence is discussed to confirm the prerequisite of any successful application of AGMOPSO. Finally, with regard to the computation performance, the proposed AGMOPSO algorithm is compared with some other multiobjective particle swarm optimization algorithms and two state-of-the-art multiobjective algorithms. The results demonstrate that the proposed AGMOPSO algorithm can find better spread of solutions and have faster convergence to the true Pareto-optimal front. PMID- 28991759 TI - The Importance of Perioperative Prophylaxis with Cefuroxime or Ceftriaxone in the Surgical Site Infections Prevention after Cranial and Spinal Neurosurgical Procedures. AB - Introduction Surgical site infections pose a significant problem in the treatment of neurosurgical procedures, regardless of the application of perioperative prophylaxis with systemic antibiotics. The infection rate in these procedures ranges from less than 1% to above 15%. Different antibiotics and administration regimes have been used in the perioperative prophylaxis so far, and there are numerous comparative studies regarding their efficiency, however, it is generally indicated that the choice thereof should be based on information and local specifics connected to the most probable bacterial causers, which would possibly contaminate the surgical site and cause infection, and moreover, the mandatory compliance with the principles of providing adequate concentration of the drug at the time of the anticipated contamination. Objective Comparing the protective effect of two perioperative prophylactic antibiotic regimes using cefuroxime (second generation cephalosporin) and ceftriaxone (third generation cephalosporin) in the prevention of postoperative surgical site infections after elective and urgent cranial and spinal neurosurgical procedures at the University Clinic for Neurosurgery in Skopje in the period of the first three months of 2016. Design of the study Prospective randomized comparative study. Outcome measures Establishing the clinical outcome represented as prevalence of superficial and deep incision and organ/space postoperative surgical site infections. Material and method We analyzed prospectively 40 patients who received parenteral antibiotic prophylaxis with two antibiotic regimes one hour before the routine neurosurgical cranial and spinal surgical procedures; the patients were randomized in two groups, according to the order of admission and participation in the study, alternately, non-selectively, those persons who fulfilled inclusion criteria were placed in one of the two programmed regimes with cefuroxime in the first, and cefotaxime in the second compared group. All relevant demographic and perioperative patient data were analyzed for both comparative groups, especially the factors known to cause disposition (predisposition) to infections. The prevalence of postoperative infections was evaluated as the primary outcome in both comparative groups, while the secondary outcome was the postoperative infection rate after cranial and spinal neurosurgical procedures at the Neurosurgical clinic in Skopje (having in consideration that so far no data have been published in this context), as well as the prevalence of the risk factors for occurrence of postoperative infections, pre-surgically in patients undergoing neurosurgical interventions locally in the Republic of Macedonia. Results A total of three cases of postoperative infections were registered, two of which classified as superficial incisional, while one case organ/space infection - meningitis (elective intervention) without etiological confirmation. Both comparative groups were statistically similar, without any statistically significant differences in the basic demographic and perioperative characteristics, especially in relation to the incidence of the factors, which, regardless of the antibiotic prophylaxis, show predisposition to postoperative infections. All three cases with infections were registered in the group of persons who received prophylaxis with ceftriaxone preoperatively, with isolated etiological S. aureus agent (elective intervention) in one of them, and methicillin resistant staphylococcus aureus (MRSA) in another (urgent intervention) with superficial incisional SSI. There was no case of SSI in the group of patients who received cefuroxime before surgery. Conclusion Administration of parenteral antibiotics before surgery reduces the incidence of postoperative infections after neurosurgical procedures, especially in cases with increased risk factors for SSI, such as ACA score of >= 2/3, the duration of the surgical intervention >= 4 hours, contaminated wound and comorbidities. Perioperative antibiotic prophylaxis should be directed to better coverage of the S.aureus arrays. PMID- 28991760 TI - Centenary of the Birth of Academician Prof. Dr. Isak Tadzer, Founder of the Pathophysiology and Nuclear Medicine in Macedonia. AB - Academician Prof. Dr. Isak Tadzer was born a hundred years ago on December 24, 1916 in Sofia. He completed the primary and secondary education at the German College in Sofia. In 1935 he began his studies at the Medical Faculty in Vienna, which he had to stop because of the annexation of Austria to Germany in 1938. He returned to Bulgaria where he continued his studies and graduated from the Medical Faculty in Sofia in 1941. During the War, 1941-1944, he was forcedly mobilized and he worked as a doctor in several villages. He was twice interned in camps in Bulgaria. In 1944 he joined the National Liberation Army and the Partisan Groups of Yugoslavia. After the liberation in 1945 he started specialization in internal medicine at the famous clinic of Prof. Chilov in Sofia. In 1946 he applied to the call by the Yugoslav government to the doctors in Bulgaria to come in aid of temporary work in our country. On the advice of the current Federal Minister of Public Health Dr. Dimitar Nestorov, Dr. Tadzer came to Skopje and was assigned to work in the Country hospital. He started specialization in internal medicine at the famous professor Ignjatovski, he established a family and decided to stay in Skopje. In 1949 Prof. Tadzer ended his specialization and he was elected an Assistant at the Department of Internal Medicine. In 1951 he left the Internal Clinic and he was elected an Assistant, and in 1952 he was elected a Docent in the subject of Pathological Physiology. In 1959 he was elected, and in 1964 he was re-elected as an Associate Professor, and in 1967 he was elected a Professor of pathophysiology at the Medical Faculty in Skopje. In the period from 1952 to 1978 he was Head of the Department and Director of the Institute of Pathophysiology. He was elected a Corresponding Member of the Macedonian Academy of Sciences and Arts in 1969, and a Full Member in 1974. In the period from 1984 to 1988 he was a Secretary of the Department of Medicine and Biology of the Academy. Prof. Tadzer has published over 300 scientific papers in the field of clinical medicine and pathological physiology, of which about 200 in journals in English, French, German and Serbo-Croatian, as well as 15 books, which include him among the most prolific pathophysiologists on the territory of former Yugoslavia and beyond. In the period from 1950 to 1966 several times he was on a vocational training in similar institutions and centers in Europe, and in 1972 he was on a study stay at many nuclear and medical laboratories in the USA. In addition to his great research activities his contribution as a teacher was of substantial influence and importance to the faculty. He was one of the greatest lectures at the Medical Faculty, the Faculty of Stomatology and the Pharmaceutical Faculty. Prof. Tadzer co-authored in most of the textbooks on pathophysiology for students of medicine, stomatology and pharmacy. He was an extraordinary physician, one of the pillars of the Macedonian medicine, he possessed universal, encyclopedic knowledge and is one of the most renowned medical workers in the second half of the 20th century in Macedonia. In addition to the scientific, medical and educational work Prof. Tadzer has especially rich social activity. He was President of the Faculty Council in 1975 76, he was Vice Dean of the Medical Faculty in 1958-60, Dean of the Faculty from 1963 to 1965, Dean of the Pharmaceutical Faculty and Vice Rector of the University from 1965 to 1967. Especially it should be noted his long-lasting activity at the Macedonian Medical Association of more than 50 years. Also, significant is his creative work within the Editorial board of the journal "Macedonian Medical Review", where for more than 15 years he was Editor in Chief or member of the Editorial board. For his complete activity Prof. Tadzer has won numerous diplomas, plaques and awards, and among them the following are emphasized: National Award of October 11, Order of Labor of Second Degree, the Award of the City of Skopje - November 13, the Charter of Dr. Trifun Panovski and the Certificate of Acknowledgement awarded by the Macedonian Medical Association for the outstanding results in advancing the medical science, practice and development of the health care and the long-term contribution and promotion of the MMA. PMID- 28991761 TI - Dimensional Stability and Acuracy of Silicone - Based Impression Materials Using Different Impression Techniques - A Literature Review. AB - A quality-made dental impression is a prerequisite for successful fixed prosthodontic fabrication and is directly dependent on the dimensional stability, accuracy and flexibility of the elastomeric impression materials, as well as on the appropriately used impression techniques. The purpose of this paper is to provide a literature review of relevant scientific papers which discuss the use of various silicone impression materials, different impression techniques and to evaluate their impact on the dimensional stability and accuracy of the obtained impressions. Scientific papers and studies were selected according to the materials used, the sample size, impression technique, storage time, type of measurements and use of spacer for the period between 2002 and 2016. In the reviewed literature several factors that influence the dimensional stability and accuracy of silicone impression molds, including the choice of the type of viscosity, impression material thickness, impression technique, retention of the impression material on the tray, storage time before the casting, number of castings, hydrophilicity of the material, release of byproducts, contraction after polymerization, thermal contraction and incomplete elastic recovery were presented. The literature review confirmed the lack of standardization of methodologies applied in the research and their great diversity. All findings point to the superiority of the addition silicone compared to the condensation silicone. PMID- 28991762 TI - Hemodynamic and Bispectral Changes During Pin Insertion in Craniotomy - Effect of Locally Infiltrated Bupivacaine. AB - Introduction Cranial pins insertion is a method for head stabilization and together with the scalp incision is one of the biggest noxious stimulus associated with arousal and rapid increase of the blood pressure leading to pathological increase of the intracranial pressure. The aim of this investigation is to study the superiority of the locally infiltrated anesthetic bupivacaine just before the skull pin insertion and the scalp incision in craniotomy under general anesthesia. Methods In the study thirty patients of both genders aged 24 72 years were included. They were categorized as ASA 1 and 2 and divided into two group of 15 patients each, group B (bupivacaine) and group S (saline). We recorded the bispectral (BIS) index, the mean arterial pressure (MAP) and the pulse rate (PR) in five time intervals: t 0-2 min before pin insertion; t 1-2 min after pin insertion; t 2-5 min after; t 3-10 min after and t 4-15 min after. Results Significant difference p<0.05 was achieved in group S for all three followed parameters: blood pressure, heart rate and bispectral index. The difference is present in all four time intervals compared to the initial one before the pin insertion. With further analysis it was demonstrated that the investigated BIS index participates the most in the overall significance in group F. Conclusion The scalp infiltration with local anesthetic bupivacaine results with stable hemodynamic parameters and stable intracranial pressure during the painful procedures as craniotomy. PMID- 28991763 TI - Normal Values of Tissue-Muscle Perfusion Indexes of Lower Limbs Obtained with a Scintigraphic Method. AB - Introduction Muscle perfusion is a physiologic process that can undergo quantitative assessment and thus define the range of normal values of perfusion indexes and perfusion reserve. The investigation of the microcirculation has a crucial role in determining the muscle perfusion. Materials and method The study included 30 examinees, 24-74 years of age, without a history of confirmed peripheral artery disease and all had normal findings on Doppler ultrasonography and pedo-brachial index of lower extremity (PBI). 99mTc-MIBI tissue muscle perfusion scintigraphy of lower limbs evaluates tissue perfusion in resting condition "rest study" and after workload "stress study", through quantitative parameters: Inter-extremity index (for both studies), left thigh/right thigh (LT/RT) left calf/right calf (LC/RC) and perfusion reserve (PR) for both thighs and calves. Results In our investigated group we assessed the normal values of quantitative parameters of perfusion indexes. Indexes ranged for LT/RT in rest study 0.91-1.05, in stress study 0.92-1.04. LC/RC in rest 0.93-1.07 and in stress study 0.93-1.09. The examinees older than 50 years had insignificantly lower perfusion reserve of these parameters compared with those younger than 50, LC (p=0.98), and RC (p=0.6). Conclusion This non-invasive scintigraphic method allows in individuals without peripheral artery disease to determine the range of normal values of muscle perfusion at rest and stress condition and to clinically implement them in evaluation of patients with peripheral artery disease for differentiating patients with normal from those with impaired lower limbs circulation. PMID- 28991764 TI - Hypoglycaemia in the Newborn. AB - AIM: Severe neonatal hypoglycaemia (HG) leads to neurologic damage, mental retardation, epilepsy, impaired cardiac performance and muscle weakness. The aim was to assess the frequency and severity of HG in a population of newborns. PATIENTS AND METHODS: We investigated 739 patients with neonatal hypoglycaemia (HG) (M:F=370:369) born at the University Clinic for Gynaecology and Obstetritics in Skopje in the period 2014-2016 and treated at the neonatal intensive care unit (NICU). 1416 babies were treated in the same period in NICU, and HG was observed in 52.18%. The birth weight was dominated by children with low birth weight: very low birth weight (VLBW)(<1500g) 253 children, (34,23%), low birth weight (1500 2500g) 402 (54.39%), appropriate for gestational age (AGA) 78(10.55%), and high birth weight (>4000g) 6 babies (0.81%). The gestational age was also dominated by children with low gestational age: gestational week (GW) 20-25 four children (0.54%), 26-30 GW 133 babies (17.99%), 31-35 GW472 (63.87%), and 36-40 GW130 neonates (17.59 %). 241 mothers (32.61%) have had an infection during pregnancy, 82 preeclampsia or eclampsia (11.09%), 20 diabetes mellitus (2.70%), 78 placental situations (placenta previa, abruption) (10.55%). In this study 47 babies (6.35%) with HG and co-morbidities died. There was a significant positive correlation between HG birth weight (p<0.01), gestational age (p<0.05), and the lowest Apgar score (p<0.01). Neonatal deaths were significantly correlated with GA (r>0,01), co-morbidities of the mothers (r>0,05) but not with the birth weight (r>0,05). In contrast, a significant positive correlation was found between convulsions and body weight (r<0.05). The lowest Apgar score was positively correlated with the gestational age (0.01), but not with the birth weight (0.05). CONCLUSION: Low birth weight, low gestational age, maternal risk factors, hypoxic-ischemic encephalopathy and neonatal infections are associated with HG and are a significant factor in overall neonatal mortality. Those results indicate that diminishing the frequency of the neonatal HG and the rates of neonatal mortality requires complex interaction of prenatal and postnatal interventions. PMID- 28991765 TI - Effects of Serenoa repens Alcohol Extract on Benign Prostate Hyperplasia. AB - An increasing tendency has recently emerged for the use of phytotherapeutic agents as alternative to commercial pharmacological agents for the treatment of benign prostate hyperplasia (BPH). The purpose of this study is to evaluate the effects of Serenoa repens alcohol extract treatment on BPH patients' symptoms and major parameters during one-year follow-up. The study was performed on 70 men aged 40 - 79 years (mean 60.58) with symptomatic BPH that were divided into a group of 40 patients treated with Serenoa repens extract (SRT) and a control group of 30 patients that received no treatment and were observed only. The following parameters were determined at the time of diagnosis (baseline), and after 6 and 12 months: prostate size, serum prostate-specific antigen (PSA) and uroflowmetry parameters including maximum flow rate (MFR), average flow rate (AFR) and post-voiding residual volume (PVRV). In addition, the relevant patient symptoms were evaluated using the International Prostate Symptom Score (IPSS) system. The patients in the SRT group showed a statistically significant increment of the average MFR and AFR values and reduction of PV relative to the control group (p<0.05). The significant differences between the proportion of patients with prostate volume >40 ml in the SRE treated group vs. control group was observed (p<0.05). The mean IPSS score was highly significantly reduced in the SRT group (p<0.01). The mild improvements of the urine flow, prostate size and IPSS score during 12 months treatment with the Serenoa repens extract indicate possible efficiency of this phytotherapeutic agent in patients with BPH. PMID- 28991766 TI - Comparative Analysis of Ultrasound Guided Central Venous Catheterization Compared to Blind Catheterization. AB - INTRODUCTION: Central venous catheterization is performed by the landmark method and ultrasound guided method. The purpose of the study was to compare the success, average number of attempts, average time to return of blood, and complication rate between the two methods. MATERIAL AND METHODS: This was a prospective study done in the Intensive Care Unit of the Acibadem Sistina Clinical Hospital, in Skopje. There were 400 patients in need of central venous catheter and they were prospectively randomized in two groups. The patients randomized in the examined-ultrasound group underwent real-time ultrasound-guided catheterization and the patients randomized in the control-landmark group were catheterized using the landmark method. Internal Jugular, Subclavian and Femoral vein were catheterized in both groups. The Overall success, success on the first attempt, time to the return of blood, number of attempts and complications at the moment of catheterization such as arterial puncture, pneumothorax and hematoma formation were the main outcome measures. RESULTS: The catheterization using the landmark method was successful in 90.5% of patients, 60.5% of which during the first attempt. The cannulation using real-time ultrasound guidance was successful in 98% of patients with a first pass success of 77%. The complication rate with the landmark method was 14.5% versus 4% with real-time ultrasound guidance p<0.05(p=0.0008). CONCLUSION: Real-time ultrasound guidance improves success, decreases number of attempts, decreases average time to the return of blood and reduces mechanical complications rate. PMID- 28991767 TI - Anorexia: Anormal Phobia of Normal Weight. AB - Anorexia nervosa is a disorder of feeding behavior associated with distortion of body image, mood disturbance and a wide variety of hormonal and metabolic abnormalities. It is supposed that the disease could be the consequence of a combination of cultural-social, psychological and biological factors. Our study confirmed that anorexia mentalis is a serious, life threatening disorder which in our country appears earlier than it was expected and that is strongly related to environmental factors (family, school, fashion, society). We showed that specific personality traits are characteristic for both, young patients and mothers. Sublimation of emotional stress by exceptional performances, accompanied by food restrictive consumption together with hypersensitivity, oppositional behavior and aggression are specific for this disorder. High levels of self-imposed standards increase the risk for psychological distress, especially for eating disorder symptomatology. Both genders could be involved as patients. Boys must be especially followed for possible psychiatric manifestation. We confirmed that the biofeedback as additional therapeutic modality is very useful. PMID- 28991768 TI - Peripheral Arterial Disease and Chronic Kidney Disease. AB - There are two points of interplay of chronic kidney (CKD) and peripheral arterial disease (PAD): CKD has been recognized as one of the main factors for presence of PAD, and PAD has been defined as a useful tool for risk stratification of CKD population. Peripheral arterial disease in patients with CKD is a frequent finding, even in those without symptoms. This review tends to describe determinants for occurrence of arterial disease in chronic kidney disease patients and necessity for its screening. PMID- 28991769 TI - Let's Go Bananas! Gren Bananas and their Health Benefits. AB - Bananas have enormous health benefits as a food for both animals and humans. They have been used as a complimentary medicine to treat pathological conditions since ancient times. Recently, there has been increased interest in the scientific validity of the beneficial effects of bananas in alleviating and treating disease conditions including, ulcers, infections, diabetes, diarrhea, colitis and blood pressure. Herein, we write on the potential therapeutic and functional benefits of certain species of bananas when consumed green as well as considering the properties of extracts from the non-fruit parts of the plant. We conclude that green bananas appear to deliver an array of health and therapeutic benefits. PMID- 28991770 TI - Transition Towards Transradial Approach Improves Outcomes of Acute Myocardial Infarction PCI. AB - INTRODUCTION AND AIM: Transradial (TRA) instead of transfemoral (TFA) approach strategy has been presented in research literature as superior access strategy especially for acute ST elevation myocardial infarction (STEMI) primary percutaneous coronary intervention (PCI). There is a paucity of registry-based data of outcomes from default TRA strategy compared to TFA. MATERIALS AND METHODS: All-comers STEMI PCI institutional Registry identified 1808 consecutive patients in time-frame of 40 months from 2007 to 2010, without making any exclusions. Moreover, we applied Propensity Score Matching (PSM) to replace randomization, address the potential confounding and selection bias. PSM derived 565 congruent pairs of patients from the groups. RESULTS: After 30 days the primary composite endpoint of major adverse cardiovascular events (MACE) was in favor of TRA 6.5% vs. 12.4% in TFA group, simultaneously secondary endpoints of death in TRA with rate of 4.8% and with rate of 10.1% in TFA. Moreover, the rate of major access related bleeding was 1.1% in TRA vs. 8.5% in TFA, in contrast the major non-access related bleeding was 1.8% and 2.4% respectively showed no significant difference. One year Kaplan Meier survival plots were in favor of TRA. CONCLUSIONS: Default transradial access strategy is associated with improved STEMI PCI outcomes. PMID- 28991771 TI - Surgical Treatment of Pleural Empyema - Our Results. AB - : Pleural infection is a frequent clinical condition. Prompt treatment has been shown to reduce morbidity, mortality and duration of hospital stay. Unfortunately, advanced stages of empyema need to use extensive surgery - decortications or thoracoplasty. Early recognition of the parapneumonic effusion and the adequate treatment with thoracentesis or pleural drainage, which is minimally invasive, is possible not to prograde the process and not to become empyema. AIM: To analyze the results of the surgical treatment in patients with empyema treated at Clinic for thoracic surgery. MATERIAL AND METHODS: In the retrospective study we analyzed 234 patients with empyema which were treated at the Clinic for Thoracic Surgery in 5 year period (2011-2015). The mean age of the patients was 51.94 years. They were treated with pleural drainage, decortications or thoracoplasty. RESULTS: With pleural drainage were treated 165/234 (70.51%) patients, of which successfully were finished 124/165 (75.15%), but 41/165 (24.85%) were indicated after the decortications. A total of 108/234 (46.15%) were treated with decortications from which, primary decortications were indicated in 67/234 (28.63%) patients. 5/234 (2.14%) patients were treated with thoracoplasty - 3 of the patients with decortications and 2 with primary indicated thoracoplasty according to the local findings, long term untreated empyema and bad general condition. The Mean hospitalization was 17.4 days, of which 13.4 days after surgery. In the group with primary drainage it was detected a lethal outcome in 7/124 (5.64%) patients, 5/105 (4.76%) in the group with decortications and 2/5 (40%) in the group with thoracoplasty. CONCLUSION: Early detection of the parapneumonic effusion and the adequate treatment will prevent the appearance of empyema. If the empyema is detected it is necessary as early as possible to start the treatment with minimally invasive pleural drainage. In earlier stages it is possible to use less invasive decortications, using VATS than the open thoracotomy decortication which is more extensive surgical intervention. PMID- 28991772 TI - Prevalence of Depression, Anxiety and Insomnia in Chronic Kidney Disease Patients and their Co-Relation with the Demographic Variables. AB - BACKGROUND: Chronic kidney disease (CKD) is an emerging health problem in both developed and developing countries. Depression, anxiety and sleep disturbances are highly prevalent in patients with chronic disease, but remain undertreated despite significant negative consequences on patients' health. Assessment of key components of mental health early in disease course will help to identify high risk subjects in whom modifying these predictors will help in providing active and healthy life in CKD patients. METHODS: We did a cross sectional study in 200 patients of CKD stage III to V-D fulfilling the eligibility criteria who were on follow up in a single tertiary care center in the state of Haryana, India. We assessed the prevalence of anxiety, depression and insomnia and their correlation with demographic variables in these patients. The structured questionnaire used in this study gathered information on respondent demographic and disease characteristics, and information obtained from the HADS and PSQI questionnaire. Factors associated with anxiety, depression and insomnia were examined by a multiple logistic regression analysis. RESULTS: The prevalence of anxiety, depression and insomnia were found to be 71%, 69% and 86.5% respectively. As the CKD stage advanced, the prevalence as well as severity of these parameters increased. Anxiety, depression and sleep quality were found to be significantly correlated to unemployment, low income, low education, urban residence and presence of co-morbidities. The anxiety, depression and insomnia scores were found to have a strong negative correlation with eGFR, hemoglobin, serum calcium (p <0.01) and a positive correlation with TLC, blood urea, serum creatinine and serum phosphate (p <0.05). CONCLUSION: We observed a high prevalence of anxiety, depression and insomnia in CKD patients. There is a need to develop strategies to accurately identify "high risk" subjects who may benefit from preventive measures before complications occur. By identifying CKD patients with high risk of developing these mental health related issues, healthcare provider may be better able to ensure the provision of appropriate rehabilitation to this population. PMID- 28991773 TI - Fibroblast Growth Factor-23: A Novel Biomarker for Cardiovascular Disease in Chronic Kidney Disease Patients. AB - Fibroblast Growth Factor (FGF)-23 increase is considered one of the earliest biochemical abnormalities in chronic kidney disease-mineral bone disorder (CKD MBD). Furthermore, accumulating data have provided evidence of a link between increased FGF-23 levels and cardiovascular morbidity and mortality in CKD patients as well as in several other populations including cardiology patients and general population. The cellular and molecular mechanisms underlying the deleterious effect of FGF-23 on the cardiovascular system are not yet completely defined and are the focus of intense research. However, animal and human studies have demonstrated important actions of FGF-23 in the heart and vessels through which could promote the development of cardiovascular complications in uremia. Moreover, significant interactions have been reported between FGF-23 and other well recognized cardiovascular risk factors such as renin-angiotensin system and inflammation which could account, at least in part, for the observed associations between FGF-23 and adverse clinical outcomes. Further studies are needed to clarify the mechanisms responsible for the pleiotropic actions of FGF-23 and moreover to identify whether it is a modifiable risk factor and a potential target of therapeutic interventions which could probably help to reduce the unacceptably high cardiovascular morbidity and mortality of CKD patients. PMID- 28991774 TI - Giant Mediastinal Thymic Cyst. AB - The authors present a rare case of giant mediastinal cyst which arises from the thymus gland, and goes down in both pleural spaces, especially in the right chest cavity where a dominant part of the cyst was present. The cyst was full with 2.5 liters of transparent fluid, and compressed surrounding structures - heart and both lungs, especially the right one which was partially collapsed. The patient was a 52 years old woman, without any clinical symptoms. Accidentally, on the screened chest X-ray a shading in the distal third of the right chest was detected. The case was well documented with a CT of the chest, and an indication for surgical treatment was made. The surgery was done successfully in general anesthesia according to the small right anterior thoracotomy from which a giant part of the cyst was mobilized, which was in the right pleural cavity, but, also, the thymus with the origin of the cyst in the anterior and superior mediastinum was completely removed. In the end, a part of the cyst which was in the left pleural cavity was removed. PMID- 28991775 TI - Evidence Based Practice in Using Antibiotics for Acute Tonsillitis in Primary Care Practice. AB - The increased use of antibiotics for acute tonsillitis is a public health problem. 80% of the antibiotic prescriptions for acute tonsillitis are done in the Primary Care practice (PCP). The inappropriate use of the antibiotic causes bacterial resistance and treatment failure. Only patients with acute tonsillitis caused by Group A beta-hemolytic streptococcus (GAS) have benefit of the antibiotic treatment, which is a predict cause in 5-20%. In order to assess the antibiotic prescribing for acute tonsillitis by the doctors in the PCP in Macedonia we use the data from the national project about antibiotic prescribing for acute respiratory tract infections which was conducted in November 2014 during a period of 4 weeks as part of the E-quality program sponsored by the IPCRG. 86 general practitioners from Macedonia have participated. The group of 1768 patients, from 4 months to 88 years of age, with diagnosis of acute tonsillitis was analyzed. The antibiotic prescriptions according to the Centor score criteria were compared to the Cochran's guidelines which are translated and recommended as national guidelines. 88.8% of the patients with acute tonsillitis were treated with antibiotics, of which 52.9% with Centor score 0 to 2 were treated inappropriate. The diagnosis is mostly made based on the clinical picture and the symptoms. Only (23.6%) of the patients were treated with antibiotics (Penicillin V and cephalexin) according to the guidelines. We concluded that there is a low adherence to the national guidelines. The clinical assessment is not accurate in determining the etiology. Also, there is a high nonadherence in prescribing the first choice of antibiotics. We emphasize the need to change the general practitioners' prescription behavior according to the guidelines. PMID- 28991776 TI - Serum and alveolar procalcitonin had a weak diagnostic value for ventilator associated pneumonia in patients with pulmonary infection score >= 6. AB - BACKGROUND: Measuring the serum and alveolar procalcitonin level as inflammatory marker in the diagnosis of ventilator-associated pneumonia (VAP) has been taken into account. In this study, serum and alveolar procalcitonin levels in patients with suspected VAP and patients with confirmed VAP were compared. METHODS: This cross-sectional study was conducted using 50 intubated intensive care unit (ICU) patients, connected to ventilator, from October 2014 to April 2015. 50 patients with clinical pulmonary infection score >=6 were divided into two groups. Patients whose bronchoalveolar lavage (BAL) has shown the growth of more than 104 CFU/mL were included in confirmed VAP group and other patients were included in suspected VAP group. Serum and alveolar procalcitonin levels were measured and compared between both groups. RESULTS: Mean age of patients was 69.10 +/- 42.13 with a range of 16-90 years, out of which 23 patients were male (46%) and 27 patients were female (54%). Moreover, patients' mean clinical pulmonary infection score was reported to be 7.02 +/- 1.07. There was a significant relationship between serum and alveolar procalcitonin in suspected patients and patients with an approved form of pneumonia (p = 0.001 and 0.027). Area under the curve for alveolar procalcitonin was 0.683 (sensitivity = 57%; specificity = 80%) and for serum procalcitonin 0.751 (sensitivity = 71%; specificity = 73%) for the diagnosis of VAP. CONCLUSION: According to the results of the present study, we can diagnose ventilator-associated pneumonia earlier and more accurately by measuring procalcitonin level (particularly alveolar type) in intensive care unit patients. PMID- 28991777 TI - Reverse flexing as a physical/mechanical treatment to mitigate fouling of fine bubble diffusers. AB - Achieving energy neutrality has shifted focus towards aeration system optimization, due to the high energy consumption of aeration processes in modern advanced wastewater treatment plants. A study on fine bubble diffuser fouling and mitigation, quantified by dynamic wet pressure (DWP), oxygen transfer efficiency and alpha was carried out in Blue Plains, Washington, DC. Four polyurethane fine bubble diffusers were installed in a pilot reactor column fed with high rate activated sludge from a full scale system. A mechanical cleaning method, reverse flexing (RF), was used to treat two diffusers (RF1, RF2), while two diffusers were kept as a control (i.e., no reverse flexing). There was a 45% increase in DWP of the control diffuser after 17 months of operation, an indication of fouling. RF treated diffusers (RF1 and RF2) did not show significant increase in DWP, and in comparison to the control diffuser prevented about 35% increase in DWP. Hence, reverse flexing potentially saves blower energy, by reducing the pressure burden on the air blower which increases blower energy requirement. However, no significant impact of the RF treatment in preventing a decrease in alpha-fouling (alphaF) of the fine pore diffusers, over time in operation was observed. PMID- 28991778 TI - Optimization of hydrometric monitoring network in urban drainage systems using information theory. AB - Regular and continuous monitoring of urban runoff in both quality and quantity aspects is of great importance for controlling and managing surface runoff. Due to the considerable costs of establishing new gauges, optimization of the monitoring network is essential. This research proposes an approach for site selection of new discharge stations in urban areas, based on entropy theory in conjunction with multi-objective optimization tools and numerical models. The modeling framework provides an optimal trade-off between the maximum possible information content and the minimum shared information among stations. This approach was applied to the main surface-water collection system in Tehran to determine new optimal monitoring points under the cost considerations. Experimental results on this drainage network show that the obtained cost effective designs noticeably outperform the consulting engineers' proposal in terms of both information contents and shared information. The research also determined the highly frequent sites at the Pareto front which might be important for decision makers to give a priority for gauge installation on those locations of the network. PMID- 28991779 TI - Estimation of hydraulic jump characteristics of channels with sudden diverging side walls via SVM. AB - Sudden diverging channels are one of the energy dissipaters which can dissipate most of the kinetic energy of the flow through a hydraulic jump. An accurate prediction of hydraulic jump characteristics is an important step in designing hydraulic structures. This paper focuses on the capability of the support vector machine (SVM) as a meta-model approach for predicting hydraulic jump characteristics in different sudden diverging stilling basins (i.e. basins with and without appurtenances). In this regard, different models were developed and tested using 1,018 experimental data. The obtained results proved the capability of the SVM technique in predicting hydraulic jump characteristics and it was found that the developed models for a channel with a central block performed more successfully than models for channels without appurtenances or with a negative step. The superior performance for the length of hydraulic jump was obtained for the model with parameters F1 (Froude number) and (h2-h1)/h1 (h1 and h2 are sequent depth of upstream and downstream respectively). Concerning the relative energy dissipation and sequent depth ratio, the model with parameters F1 and h1/B (B is expansion ratio) led to the best results. According to the outcome of sensitivity analysis, Froude number had the most significant effect on the modeling. Also comparison between SVM and empirical equations indicated the great performance of the SVM. PMID- 28991780 TI - Influence of chemically enhanced primary treatment on anaerobic digestion and dewaterability of waste sludge. AB - To lower energy consumption at a sewage treatment plant (STP), primary settling could be enhanced to direct more chemical oxygen demand (COD) to anaerobic digestion (AD) for increased biogas production and decreased aeration. Primary settling can be chemically enhanced by applying flocculation aids (FAs). FAs are refractory compounds that may affect all sludge treatment facilities. In this study the consequences are investigated of the application of FAs for chemically enhanced primary treatment (CEPT) on AD and subsequent dewatering of digested sludge in a conventional STP. It was found that FAs maintain their effect throughout all sludge processing facilities. With CEPT, more readily degradable solids were removed, resulting in a higher bio methane potential of the primary sludge. In AD, FAs lowered the viscosity; meanwhile an increased hydrolysis rate was observed. But FAs also partially irreversibly bound substrate in such way that it is not available for biological degradation anymore. In subsequent dewatering of digested sludge, a higher dry solids concentration was observed with CEPT. A computer simulation showed that in a conventional STP, CEPT would not be economically feasible. However, several benefits were discussed that can make CEPT an interesting option for future low COD/N-tolerant STPs with, for example, Anammox processes for N removal. PMID- 28991781 TI - A heterogeneous computing accelerated SCE-UA global optimization method using OpenMP, OpenCL, CUDA, and OpenACC. AB - The shuffled complex evolution optimization developed at the University of Arizona (SCE-UA) has been successfully applied in various kinds of scientific and engineering optimization applications, such as hydrological model parameter calibration, for many years. The algorithm possesses good global optimality, convergence stability and robustness. However, benchmark and real-world applications reveal the poor computational efficiency of the SCE-UA. This research aims at the parallelization and acceleration of the SCE-UA method based on powerful heterogeneous computing technology. The parallel SCE-UA is implemented on Intel Xeon multi-core CPU (by using OpenMP and OpenCL) and NVIDIA Tesla many-core GPU (by using OpenCL, CUDA, and OpenACC). The serial and parallel SCE-UA were tested based on the Griewank benchmark function. Comparison results indicate the parallel SCE-UA significantly improves computational efficiency compared to the original serial version. The OpenCL implementation obtains the best overall acceleration results however, with the most complex source code. The parallel SCE-UA has bright prospects to be applied in real-world applications. PMID- 28991782 TI - rGO/MnO2 nanowires for ultrasonic-combined Fenton assisted efficient degradation of Reactive Black 5. AB - Reduced graphene oxide (rGO) coated manganese dioxide (MnO2) nanowires (NWs) were prepared by the hydrothermal method. Raman spectra confirmed the presence of rGO and the Brunauer-Emmett-Teller surface area of rGO/MnO2 NWs was found to be 59.1 m2g-1. The physico-chemical properties of prepared catalysts for the degradation of Reactive Black 5 (RB5) dye were investigated. 84% of RB5 dye in hydrogen peroxide solution was successfully degraded using rGO/MnO2 NWs, while only 63% was successfully degraded with pristine alpha-MnO2 NWs in 60 min owing to the smaller crystallite size and large surface area. Further, the ultrasonic-combined Fenton process significantly enhanced the degradation rate to 95% of RB5 by the catalyst rGO/MnO2 NWs due to synergistic effects. The decomposition products identified using gas chromatography-mass spectrometry revealed a higher production rate of fragments in the ultrasonic-combined Fenton process. Therefore, rGO/MnO2 NWs with the ultrasonic-combined Fenton process is an efficient catalyst for the degradation of RB5, and may be used for environmental protection. PMID- 28991783 TI - Difficulties and modifications in the use of available methods for hydraulic conductivity measurements in highly clogged horizontal subsurface flow constructed wetlands. AB - Despite the fact that several authors consider the available measurement methods of hydraulic conductivity (ks) suitable for a good representation of the bed condition and clogging potential in horizontal subsurface flow constructed wetlands, others have questioned their adequacy. In this work, hydraulic conductivity measurements with conventional and modified methods were undertaken in two small full-scale units, one planted with cattail (Typha latifolia) and the other unplanted. Both units had already been operating for seven years and showed a high degree of clogging. It was observed that the use of the falling head method, with the introduction of the tubes during the test, provided results without a clear spatial trend. On the other hand, tests done on monitoring wells inserted during construction time showed, as expected, ks increasing with the horizontal distance from the inlet, but without reflecting actual field conditions. It was observed that, as the bed became more clogged, the use of the reported methods became more complex, suggesting the need of other methodologies. The use of planted fixed reactors (removable baskets installed in the bed) with evaluation of ks at constant head in the laboratory showed potential for the characterization of the hydrodynamic properties of the porous medium. PMID- 28991784 TI - Preparation of magnetic imprinted graphene oxide composite for catalytic degradation of Congo red under dark ambient conditions. AB - Magnetic imprinted N-doped P25/Fe3O4-graphene oxide (MIGNT) was prepared with methyl orange as the dummy template and pyrrole as functional monomer for catalytic degradation of Congo red (CR). Hummers method and the hydrothermal method were used to synthesize Fe3O4-GO and N-doped P25, respectively. The results of adsorption and degradation experiments showed that the adsorption capacity and catalytic degradation ability of the imprinted composite for CR were obviously higher than those of a non-imprinted one. Moreover, the effect factors on degradation efficiency of CR, such as the initial concentration of CR, catalysis time, pH of the solution and temperature, were investigated. The MIGNT was characterized by X-ray diffraction, Fourier transform infrared spectroscopy, transmission electron microscopy, a physical property measurement system and a thermal gravimetric analyzer. The degradation products of CR were detected with high performance liquid chromatography and a mass spectrometer. The MIGNT was a brand-new imprinted composite and had high degradation efficiency for CR under dark ambient conditions. The MIGNT could be recycled conveniently, due to its magnetic property, and could be used as an effective, environmentally friendly and low-cost catalytic degradation material for the treatment of water contaminated by CR. PMID- 28991785 TI - Superheated water pretreatment combined with CO2 activation/regeneration of the exhausted activated carbon used in the treatment of industrial wastewater. AB - This paper examines a novel method of regenerating saturated activated carbon after adsorption of complex phenolic, polycyclic aromatic hydrocarbons with low energy consumption by using superheated water pretreatment combined with CO2 activation. The effects of the temperature of the superheated water, liquid-solid ratio, soaking time, activation temperature, activation time, and CO2 flow rate of regeneration and adsorption of coal-powdered activated carbon (CPAC) were studied. The results show that the adsorption capacity of iodine values on CPAC recovers to 102.25% of the fresh activated carbon, and the recovery rate is 79.8% under optimal experimental conditions. The adsorption model and adsorption kinetics of methylene blue on regenerated activated carbon (RAC) showed that the adsorption process was in accordance with the Langmuir model and the pseudo second-order kinetics model. Furthermore, the internal diffusion process was the main controlling step. The surface properties, Brunauer-Emmett-Teller (BET) surface area, and pore size distribution were characterized by Fourier transform infrared spectroscopy (FT-IR) and BET, which show that the RAC possesses more oxygen-containing functional groups with a specific surface area of 763.39 m2 g-1 and a total pore volume of 0.3039 cm3 g-1. Micropores account for 79.8% and mesopores account for 20.2%. PMID- 28991786 TI - Characteristics and adsorption study of the activated carbon derived from municipal sewage sludge. AB - Sewage sludge-based activated carbon is proved to be an efficient and low-cost adsorbent in treatment of various industrial wastewaters. The produced carbon had a well-developed pore structure and relatively low Brunauer-Emmett-Teller (BET) surface area. Adsorptive capacity of typical pollutants, i.e. copper Cu(II) and methylene blue (MB) on the carbon was studied. Adsorptions were affected by the initial solution pH, contact time and adsorbent dose. Results showed that adsorption of Cu(II) and MB on the produced carbon could reach equilibrium after 240 min. The average removal rate for Cu(II) on the carbon was high, up to 97% in weak acidic conditions (pH = 4-6) and around 98% for MB in a very wide pH range (pH = 2-12). The adsorption kinetics were well fitted by the pseudo-second order model, and both Langmuir and Freundlich isotherm models could well describe the adsorption process at room temperature. The theoretical maximum adsorption capacities of Cu(II) and MB on sewage sludge-based activated carbon were 114.94 mg/g and 125 mg/g, respectively. Compared with commercial carbon, the sewage sludge-based carbon was more suitable for heavy metal ions' removal than dyes'. PMID- 28991787 TI - Biosurfactant production by Mucor circinelloides on waste frying oil and possible uses in crude oil remediation. AB - Biosurfactants are biocompatible surface active agents which many microorganisms produce. This study investigated the production of biosurfactants by Mucor circinelloides. The effects of different factors on biosurfactant production, including carbon sources and concentrations, nitrogen sources, and iron (II) concentration, were studied and the optimum condition determined. Finally, the strain's ability to remove the crude oil and its relationship with biosurfactant production was evaluated. The results showed that M. circinelloides could reduce the surface tension of the culture medium to 26.6 mN/m and create a clear zone of 12.9 cm diameter in an oil-spreading test. The maximum surface tension reduction was recorded 3 days after incubation. The optimum condition for biosurfactant production was achieved in the presence of 8% waste frying oil as a carbon source, 2 g/L yeast extract as a nitrogen source, and 0.01 mM FeSO4. M. circinelloides could consume 8% waste frying oil in 5 days of incubation, and 87.6% crude oil in 12 days of incubation. A direct correlation was observed between oil degradation and surface tension reduction in the first 3 days of fungal growth. The results showed that the waste frying oil could be recommended as an inexpensive oily waste substance for biosurfactant production, and M. circinelloides could have the potential to treat waste frying oil. According to the results, the produced crude biosurfactant or fungal strain could be directly used for the mycoremediation of crude oil contamination in oil fields. PMID- 28991788 TI - The investigation of paper mill industry wastewater treatment and activated sludge properties in a submerged membrane bioreactor. AB - The paper mill industry produces high amounts of wastewater and, for this reason, stringent discharge limits are applied for sustainable reclamation and reuse of paper mill industry wastewater in many countries. Submerged membrane bioreactor (sMBR) systems can create new opportunities to eliminate dissolved substances present in paper mill wastewater including. In this study, a sMBR was operated for the treatment of paper mill industry wastewater at 35 h of hydraulic retention time (HRT) and 40 d of sludge retention time (SRT). The chemical oxygen demand (COD), NH3-N and total phosphorus (TP) removal efficiencies were found to be 98%, 92.99% and 96.36%. The results demonstrated that sMBR was a suitable treatment for the removal of organic matter and nutrients for treating paper mill wastewater except for the problem of calcium accumulation. During the experimental studies, it was noted that the inorganic fraction of the sludge increased as a result of calcium accumulation in the reactor and increased membrane fouling was observed on the membrane surface due to the calcification problem encountered. The properties of the sludge, such as extracellular polymeric substances (EPS) and soluble microbial products (SMP), relative hydrophobicity, zeta potential and floc size distribution were also monitored. According to the obtained results, the total EPS was found to be 43.93 mg/gMLSS and the average total SMP rejection by the membrane was determined as 66.2%. PMID- 28991789 TI - The role of Arthrobacter viscosus in the removal of Pb(II) from aqueous solutions. AB - The aim of this paper was to establish the optimum parameters for the biosorption of Pb(II) by dead and living Arthrobacter viscosus biomass from aqueous solution. It was found that at an initial pH of 4 and 26 degrees C, the dead biomass was able to remove 97% of 100 mg/L Pb(II), while the living biomass removed 96% of 100 mg/L Pb(II) at an initial pH of 6 and 28 +/- 2 degrees C. The results were modeled using various kinetic and isotherm models so as to find out the mechanism of Pb(II) removal by A. viscosus. The modeling results indicated that Pb(II) biosorption by A. viscosus was based on a chemical reaction and that sorption occurred at the functional groups on the surface of the biomass. Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy coupled with energy dispersive X-ray microanalysis (SEM-EDX) analyses confirmed these findings. The suitability of living biomass as biosorbent in the form of a biofilm immobilized on star-shaped polyethylene supports was also demonstrated. The results suggest that the use of dead and living A. viscosus for the removal of Pb(II) from aqueous solutions is an effective alternative, considering that up to now it has only been used in the form of biofilms supported on different zeolites. PMID- 28991790 TI - Prediction of biochemical oxygen demand at the upstream catchment of a reservoir using adaptive neuro fuzzy inference system. AB - The aim of this study is to examine the potential of adaptive neuro fuzzy inference system (ANFIS) to estimate biochemical oxygen demand (BOD). To illustrate the applicability of ANFIS method, the upstream catchment of Feitsui Reservoir in Taiwan is chosen as the case study area. The appropriate input variables used to develop the ANFIS models are determined based on the t-test. The results obtained by ANFIS are compared with those by multiple linear regression (MLR) and artificial neural networks (ANNs). Simulated results show that the identified ANFIS model is superior to the traditional MLR and nonlinear ANNs models in terms of the performance evaluated by the Pearson coefficient of correlation, the root mean square error, the mean absolute percentage, and the mean absolute error. These results indicate that ANFIS models are more suitable than ANNs or MLR models to predict the nonlinear relationship within the variables caused by the complexity of aquatic systems and to produce the best fit of the measured BOD concentrations. ANFIS can be seen as a powerful predictive alternative to traditional water quality modeling techniques and extended to other areas to improve the understanding of river pollution trends. PMID- 28991791 TI - Kinetic study of Reactive Black 5 degradation by Fe2+/S2O82- process via interactive model-based response surface methodology. AB - This study aimed to kinetically discover optimal conditions on characteristics of Reactive Black 5 decolorization/degradation via ferrous (Fe2+)-activated potassium persulfate (PS). Monod-like kinetics and interactive model-based response surface methodology (RSM) were applied to fitting and predict optimize treatment. Biodegradability of the intermediates was also tested by shaking culture with two species (Proteus hauseri ZMd44 and Shewanella sp. WLP72). Results showed that the optimal degradation efficiency was predicted (through RSM) as pH 3.72, (PS) = 0.39 mM, and (Fe2+) = 0.29 mM. The transformation products (dl-4-hydroxymandelic acid, benzoic acid, benzene, formic acid, oxalic acid and acetic acid) were less toxic than the original dye solution. According to those results, clean-up of dye pollutants by the Fe2+/S2O82- process is feasible as a pre-processing for the biodegradation, and the predicted optimal conditions are meaningful for further industry utilization. PMID- 28991792 TI - Automatic control of the effluent turbidity from a chemically enhanced primary treatment with microsieving. AB - For chemically enhanced primary treatment (CEPT) with microsieving, a feedback proportional integral controller combined with a feedforward compensator was used in large pilot scale to control effluent water turbidity to desired set points. The effluent water turbidity from the microsieve was maintained at various set points in the range 12-80 NTU basically independent for a number of studied variations in influent flow rate and influent wastewater compositions. Effluent turbidity was highly correlated with effluent chemical oxygen demand (COD). Thus, for CEPT based on microsieving, controlling the removal of COD was possible. Thereby incoming carbon can be optimally distributed between biological nitrogen removal and anaerobic digestion for biogas production. The presented method is based on common automation and control strategies; therefore fine tuning and optimization for specific requirements are simplified compared to model-based dosing control. PMID- 28991793 TI - Biotic manganese oxidation coupled with methane oxidation using a continuous-flow bioreactor system under marine conditions. AB - Biogenic manganese oxides (BioMnOx) can be applied for the effective removal and recovery of trace metals from wastewater because of their high adsorption capacity. Although a freshwater continuous-flow system for a nitrifier-based Mn oxidizing microbial community for producing BioMnOx has been developed so far, a seawater continuous-flow bioreactor system for BioMnOx production has not been established. Here, we report BioMnOx production by a methanotroph-based microbial community by using a continuous-flow bioreactor system. The bioreactor system was operated using a deep-sea sediment sample as the inoculum with methane as the energy source for over 2 years. The BioMnOx production became evident after 370 days of reactor operation. The maximum Mn oxidation rate was 11.4 mg L-1 day-1. An X-ray diffraction analysis showed that the accumulated BioMnOx was birnessite. 16S rRNA gene-based clone analyses indicated that methanotrophic bacterial members were relatively abundant in the system; however, none of the known Mn oxidizing bacteria were detected. A continuous-flow bioreactor system coupled with nitrification was also run in parallel for 636 days, but no BioMnOx production was observed in this bioreactor system. The comparative experiments indicated that the methanotroph-based microbial community, rather than the nitrifier-based community, was effective for BioMnOx production under the marine environmental conditions. PMID- 28991794 TI - Microbiological and physicochemical evaluation of the effluent quality in a membrane bioreactor system to meet the legislative limits for wastewater reuse. AB - The aim of this study was to assess the efficacy and effluent quality of a pilot scale intermittently aerated and fed, externally submerged membrane bioreactor (MBRes) treating municipal wastewater. The effluent quality of the MBRes was evaluated regarding system ability to comply with the Greek legislative limits for restricted and unrestricted wastewater reuse. The average permeate flux was 13.9 L m-2 h-1, while the transmembrane pressure remained above the level of -110 mbar. Experimental data showed that biochemical oxygen demand, chemical oxygen demand, total nitrogen, PO43-- P and total suspended solids removal efficiencies were 97.8, 93.1, 89.6, 93.2 and 100%, respectively, whereas turbidity was reduced by 94.1%. Total coliforms and Escherichia coli were fully eliminated by ultrafiltration and disinfection methods, such as chlorination and ultraviolet radiation. In agreement with the Greek legislation (Joint Ministerial Decree 145116/11) and the guidelines recommended for the Mediterranean countries, the disinfected effluent of the MBRes system can be safely reused directly for urban purposes. PMID- 28991795 TI - Nonspontaneous and multilayer adsorption of malachite green dye by Acacia nilotica waste with dominance of physisorption. AB - Adsorption of the hazardous dye malachite green (MG) by Acacia nilotica (AN) waste was investigated. Batch process variables for the adsorption of MG by AN were optimized. The mechanisms involved in the adsorption of MG by AN were explored using isotherms and kinetic models. The thermodynamic parameters were calculated to determine the spontaneity and thermal nature of the MG adsorption reaction. The maximum equilibrium adsorption capacity of AN was found to be 113.26 mg/g at 30 degrees C. The MG adsorption data revealed that AN adsorbs MG by multilayer adsorption, as shown by the better fit of the data to the Freundlich and Halsey models (R2 = 0.99) rather than to the Langmuir model. Multilayer adsorption involves physisorption, which was confirmed by the E value (mean free energy of adsorption) of the Dubinin-Radushkevich model (6.52 kJ/mol). Surface diffusion was found to be the main driving force for MG adsorption by AN. The MG adsorption reaction was endothermic, based on the enthalpy, and was controlled by the entropy of the system in the T1 temperature range (30 to 40 degrees C), while the opposite trend was observed in the T2 range (40 to 50 degrees C). Moreover, MG adsorption by AN was found to be nonspontaneous at all temperatures. PMID- 28991796 TI - Continuous transformation of chiral pharmaceuticals in enzymatic membrane bioreactors for advanced wastewater treatment. AB - This study demonstrates continuous enantiomeric inversion and further biotransformation of chiral profens including ibuprofen, naproxen and ketoprofen by an enzymatic membrane bioreactor (EMBR) dosed with laccase. The EMBR showed non-enantioselective transformations, with high and consistent transformation of both (R)- and (S)-ibuprofen (93 +/- 6%, n = 10), but lower removals of both enantiomers of naproxen (46 +/- 16%, n = 10) and ketoprofen (48 +/- 17%, n = 10). Enantiomeric analysis revealed a bidirectional but uneven inversion of the profens, for example 14% inversion of (R)- to (S)- compared to 4% from (S)- to (R)-naproxen. With redox-mediator addition, the enzymatic chiral inversion of both (R)- and (S)-profens remained unchanged, although the overall conversion became enantioselective; except for (S)-naproxen, the addition of redox mediator promoted the degradation of (R)-profens only. PMID- 28991797 TI - Ochrobactrum anthropi used to control ammonium for nitrate removal by starch stabilized nanoscale zero valent iron. AB - In this study, the hydrogenotrophic denitrifying bacterium Ochrobactrum anthropi was added in to the process of nitrate removal by starch-stabilized nanoscale zero valent iron (nZVI) to minimize undesirable ammonium. The ammonium control performance and cooperative mechanism of this combined process were investigated, and batch experiments were conducted to discuss the effects of starch-stabilized nZVI dose, biomass, and pH on nitrate reduction and ammonium control of this system. The combined system achieved satisfactory performance because the anaerobic iron corrosion process generates H2, which is used as an electron donor for the autohydrogenotrophic bacterium Ochrobactrum anthropi to achieve the autohydrogenotrophic denitrification process converting nitrate to N2. When starch-stabilized nZVI dose was increased from 0.5 to 2.0 g/L, nitrate reduction rate gradually increased, and ammonium yield also increased from 9.40 to 60.51 mg/L. Nitrate removal rate gradually decreased and ammonium yield decreased from 14.93 to 2.61 mg/L with initial OD600 increasing from 0.015 to 0.080. The abiotic Fe0 reduction process played a key role in nitrate removal in an acidic environment and generated large amounts of ammonium. Meanwhile, the nitrate removal rate decreased and ammonium yield also reduced in an alkaline environment. PMID- 28991798 TI - Iron removal in highly contaminated acid mine drainage using passive biochemical reactors. AB - Passive biochemical reactors (PBRs) are a viable alternative to neutralization plants for the treatment of acid mine drainage (AMD) because they require lower investment costs and use residual materials. However, high iron (Fe) concentrations (>=0.5 g/L) in AMD are challenging for their long-term efficiency. Sorption and precipitation are the main Fe removal mechanisms, but the relative importance of each is mostly unknown. In this study, locally available natural materials (organic and inorganic) were characterized and tested for their performance in Fe removal from highly contaminated AMD (pH 3.5, 4 g/L of Fe, and 9 g/L of sulfate). Iron retention capacity of the materials was then evaluated and the efficiency of eight mixtures of materials was compared through 40-day laboratory batch tests. All batch-type PBRs increased the pH up to 6.5 and decreased dissolved metals concentrations, including Fe, up to 99%. Results showed that organic residual materials (manures, municipal wastewater sludge, and compost) were the best substrates for Fe removal.These findings allowed for the selection of three reactive mixtures with distinct characteristics (mixture #1 - 30% organic wastes; mixture #4 - 50% calcite; and mixture #7 - 50% sand) to be further evaluated in column type PBRs. PMID- 28991799 TI - Application of leaching tests on phosphogypsum by infiltration-percolation. AB - The phosphoric acid production obtained by attacking phosphate rock by sulphuric acid cogenerates considerable quantities of phosphogypsum. The world cogeneration is estimated about 100-280 Mt per year. In another context of sustainable development, the phosphate chemical industry develops different ways of phosphogypsum valorization, which makes its storage stack in a suitable way for its potential use as an industrial by-product. Although, this storage can cause an environmental impact largely due to the transfer of trace elements (TEs) to groundwater by leaching. It is therefore important to evaluate the impact linked to the storage in order to limit this transfer. The evaluation is usually performed through leaching tests in columns or reactor. In this work, leaching tests were performed in columns by infiltration-percolation on two filter mediums: phosphogypsum and synthetic sandy soils. The results showed that the phosphogypsum is acting as a filter, which retains and releases the TEs. Most of these TEs (Pb, Se, Ag, Zn and Cu) were highly retained in the synthetic soils surfaces and their contents in waters were considerably lower than the maximum contaminant levels (MCLs). Although As, Cd, Cr and Ni were strongly transferred to groundwater, their respective contents were higher than the MCLs. PMID- 28991801 TI - Migration and speciation of heavy metal in salinized mine tailings affected by iron mining. AB - The negative effects of heavy metals have aroused much attention due to their high toxicity to human beings. Migration and transformation trend of heavy metals have a close relationship with soil safety. Researching on migration and transformation of heavy metals in tailings can provide a reliable basis for pollution management and ecosystem restoration. Heavy metal speciation plays an important role in risk assessment. We chose Anshan tailings for our study, including field investigations and laboratory research. Four typical heavy metal elements of mine tailings {Fe (373.89 g/kg), Mn (2,303.80 mg/kg), Pb (40.99 mg/kg) and Cr (199.92 mg/kg)} were studied via Tessier test in vertical and horizontal direction. The main speciation of heavy metals in Anshan tailings was the residual. However, heavy metals have a strong ability for migration and transformation in vertical and horizontal directions. Its tendency to change from stable to unstable speciation results in increasing bioavailability and potential bioavailability. Fe, Mn, Pb and Cr showed different ability in the migration and transformation process (Mn > Pb > Fe > Cr) depending on the characteristics of heavy metals and physicochemical properties of the environment. PMID- 28991800 TI - Pretreatment of brewery effluent to cultivate Spirulina sp. for nutrients removal and biomass production. AB - Due to the low concentration of nitrate and high contents of organics, brewery effluent was not suitable for the cultivation of Spirulina sp. This work changed the nutrient profile of brewery effluent effectively by dilution, addition of nitrate, and anaerobic digestion. The result showed that the optimum dilution rate and NaNO3 addition for brewery effluent were 20% and 0.5 g/L, respectively. Spirulina sp. grown in pretreated brewery effluent produced 1.562 mg/L biomass and reduced concentrations of nutrients to reach the permissible dischargeable limits. In addition, Spirulina sp. grown in pretreated brewery effluent had much higher protein content and oil content. So the appropriate treatment converted brewery effluent into a nutrient balanced medium for algae cultivation and alleviated the potential environmental problems. Pretreatment procedure developed in this work is an effective way to realize the sustainable utilization of brewery effluent and produce algal biomass with valuable nutrients. PMID- 28991802 TI - Cactus Opuntia as natural flocculant for urban wastewater treatment. AB - The cactus tree, species Opuntia ficus-indica, is a primary material of many products in various domains such as cosmetics, medicine and nutrition. In the present work, we assess its potential as a flocculant. We tried a technique which adopts three sequential treatments that used coagulation, flocculation and sedimentation processes under certain operating conditions. For this purpose, we used the aluminum sulfate (AS) as coagulant and fresh cladodes juice (FCJ) as bioflocculant. All tests were carried out on high turbid urban wastewater collected from the Metlaoui's Wastewater Treatment Plant (MWTP) (in Gafsa in southwest Tunisia). Experiments with this couple AS/FCJ show very interesting results: a high-removal of turbidity (TUR), suspended solids (SS) and chemical oxygen demand (COD). The percentages of abatement of these parameters are respectively 93.65%, 82.75% and 64.30%. The experimental results of the present study prove that the turbidity, SS and COD removal efficiency of new technique is superior to that of conventional process (with only AS). By this technique, we save 50% in AS dose. Moreover, flocs formed by the treatment using AS/FCJ are coarse and readily settleable. PMID- 28991803 TI - Enhanced flux performance of polyamide composite membranes prepared via interfacial polymerization assisted with ethyl formate. AB - A novel thin film composite (TFC) polyamide reverse osmosis membrane was prepared via the interfacial polymerization of m-phenylene diamine (MPD) in aqueous phase and 1,3,5-trimesoyl chloride (TMC) in organic phase on a polysulfone ultrafiltration support by assisting with ethyl formate as a co-solvent added in the organic phase. The ethyl formate added in the organic phase is intended to form a narrow miscibility zone, which leads to the thicker reaction zone. The multi-layered loose polyamide structure with larger pore size was formed due to the thicker reaction zone and lower content of MPD. The enhanced hydrophilicity of the membrane was proved by the decreased water contact angle. Water flux was measured at 1.6 MPa with 2,000 ppm NaCl aqueous solution. Compared to the TFC membrane prepared without ethyl formate, the water flux across the TFC membrane with ethyl formate in the organic phase increased with the increased ethyl formate content (from 23 to 45 L/(m2 h)) and the salt rejection remained at a high level (>90%). The ethyl formate can be used as a co-solvent to effectively enhance the performance of the TFC membrane. PMID- 28991804 TI - Continuous biosorption of nickel from aqueous solution using Chrysanthemum indicum derived biochar in a fixed-bed column. AB - The biosorption capability of Chrysanthemum indicum to remove nickel ions from aqueous solution in a fixed-bed column was examined in this study. Native C. indicum flower waste was improved for its biosorptive potential by pyrolysis to obtain its biochar form and, thereby, both raw (CIF-R) and biochar (CIF-BC) forms of the flower were used for Ni(II) removal. Fixed bed column studies were conducted to examine the influence of bed height (1.0-3.0 cm), flow rate (1.0-5.0 mL min-1) and initial metal ion concentration (25-75 mg L-1). The breakthrough curves (Cout/Cin vs time) were modelled using different dynamic adsorption models, viz. Adams-Bohart, Thomas and Yoon-Nelson model. Interpretation of the data revealed a favorable correlation with the Thomas model with higher R2 values and closer model-predicted and experimental biosorption capacity values. The equilibrium uptake capacity of CIF-R and CIF-BC for Ni(II) were found to be 14.02 and 29.44 mg g-1, respectively. Further, the column was regenerated using HCl as eluent, to desorb the adsorbed Ni(II) ions. The experimental results implied and affirmed the suitability of the biosorbents for nickel ion biosorption with its nature being favorable, efficient, and environmentally friendly. PMID- 28991805 TI - A bio-electrochemical membrane system for more sustainable wastewater treatment with MnO2/PANI modified stainless steel cathode and photosynthetic provision of dissolved oxygen by algae. AB - A competitive sewage treatment technology should meet the standard of water quality requirement and accomplish recovery of potential energy. This study presents such a new system, with coupled membrane bioreactor-microbial fuel cell features, which can not only treat wastewater, but also recovers energy from wastewater by electricity generation, and form a new resource by photosynthesis while providing the dissolved oxygen by algae. Specifically, in the system, the MnO2/polyaniline is used to modify the stainless steel mesh and to function well as system membrane and cathode, with satisfactory filtration and catalysis performance. The system enables continuous wastewater treatment with stable pollutant removal and electricity generation. Under the membrane flux of 119.4 Lm 2 h-1, a maximum power density of 1.2 W m-3 can be achieved, the algae multiply 6.1 times, and satisfactory wastewater treatment effect is achieved. PMID- 28991806 TI - Preparation of a novel chloromethylated polystyrene-2-mercapto-1,3,4-thiadiazole chelating resin and its adsorption properties and mechanism for separation and recovery of Hg(II) from aqueous solutions. AB - With an efficient methodology, a novel chloromethylated polystyrene-g-2-mercapto 1,3,4-thiadiazole chelating resin (MTR resin) was prepared via a one-step reaction. The structure of MTR resin was characterized by elements analysis, Fourier transform infrared spectroscopy, thermogravimetric analysis, and scanning electron microscopy. Meanwhile, the adsorption properties of the resin for Hg(II) were investigated by batch and column experiments. The results showed that the resin possessed much better adsorption capability for Hg(II) than for other metal ions. The statically and the dynamic saturated adsorption capacities were 343.8 mg/g and 475.1 mg/g. The adsorption kinetic and equilibrium data were well fitted to the second-order model and the Langmuir isotherm model, respectively. Desorption of mercury from the resin can be achieved using 30 mL of 2 mol/L HCl 5% thiourea solution with a desorption ratio of 92.3%. Compared with other absorbents, MTR resin was greatly conserve natural resources and reduce the cost. PMID- 28991807 TI - Assessment of Ambient Exposures Firefighters Encounter While at the Fire Station: An Exploratory Study. AB - OBJECTIVE: Firefighters are at an increased risk for many types of cancer. Although most studies on this topic focus on exposures encountered while fighting fires, exposures at the fire station are also cause for concern. This pilot study aimed to describe air quality within a few fire stations in and around Boston, Massachusetts, and to investigate physical and organizational factors that may influence levels of contaminants in stations. METHODS: Air sampling of particulate matter less than 2.5 MUm in diameter (PM2.5) and particle-bound polycyclic aromatic hydrocarbons (PAHs) was completed at four fire stations in Spring, 2016. Sampling occurred in the kitchen, truck bay, and just outside the station. Data were analyzed to assess differences between and within stations. Interviews (n =7) were conducted with officers at each station to explore health and safety-related organizational policies and practices. Interviews were transcribed and analyzed for thematic content. RESULTS: At each station, levels of contaminants were higher in the truck bays than either the outdoors or kitchen, and varied the most throughout the day. The station with the highest exposures in the truck bay had the lowest levels in the kitchen, which was possibly explained by new building materials and effective separation between building zones. The age and layout of the stations appeared to determine the extent to which policies favoring exhaust capture were implemented. CONCLUSION: Levels of PM2.5 and PAH inside fire stations may contribute to firefighter cancer risk. Through understanding contaminant variability, we can begin to design and test interventions that improve cancer prevention. PMID- 28991809 TI - A Novel Presentation of Bladder Mass: Self-palpation by a Patient With Cystocele. AB - INTRODUCTION: This case describes diagnosis of a T2 transitional cell carcinoma in an 89-year-old woman with known cystocele and urinary retention managed with clean intermittent self-catheterization. CASE: While self-catheterizing, the patient noted a palpable mass in her cystocele. She eventually pursued urologic evaluation of this mass, which ultimately led to her diagnosis. This is the first reported case of transitional cell carcinoma being found on self-examination by palpating a cystocele. PMID- 28991808 TI - Are Workplace Psychosocial Factors Associated With Work-Related Injury in the US Workforce?: National Health Interview Survey, 2010. AB - INTRODUCTION: Psychosocial hazards in the workplace may adversely impact occupational and general health, including injury risk. METHODS: Among 16,417 adult workers in the 2010 National Health Interview Survey Occupational Health Supplement, weighted prevalence estimates were calculated for work-related injuries (WRI) and any injuries. The association between injury and psychosocial occupational hazards (job insecurity, work-family imbalance, hostile work environment) was assessed adjusting for sociodemographic and occupational factors. RESULTS: WRI prevalence was 0.65% (n = 99); any injury prevalence was 2.46% (n = 427). In multivariable models job insecurity, work-family imbalance, and hostile work environment were each positively associated with WRI prevalence (odds ratio [OR]: 1.60, 95% CI: 0.97-2.65; OR: 1.69, 95% CI 0.96-2.89; and 2.01, 95% CI 0.94-4.33, respectively). CONCLUSIONS: Stressful working conditions may contribute to injuries. There is need for ongoing surveillance of occupational psychosocial risk factors and further study of their relationship with injury. PMID- 28991810 TI - Inferior Transplant Outcomes of Adolescents and Young Adults Bridged with a Ventricular Assist Device. AB - Adolescents, who are thought to have compliance issues, are well known to have poor heart transplant (HTx) outcomes. This "effect" has recently been demonstrated to extend to age 29. The study sought to investigate whether the poor outcomes for HTx related to adolescent age are also observed in recipients who are bridged to transplant (BTT) with a ventricular assist device (VAD) and whether this effect extends beyond the standard definition of adolescent age 12 18 years. All HTx BTT with a VAD in recipients 8-39 years were identified in the United States Organ Sharing (UNOS) database (1 January 2005 to 30 June 2016). Based on the Kaplan-Meier survival comparison for age year, patients were divided into three groups: Group 1 (8-14 years), group 2 (15-29 years), and group 3 (30 39 years). A total of 1,848 HTx were bridged with a VAD. A decline in post-HTx 5 years survival was noted after 14 years of age, which improved at around 30 years of age. Group 1 had 237 (13%) HTx, group 2 had 787 (43%) HTx, and group 3 had 823 (44%) HTx. Group 2 (15-29 years) had worse post-HTx survival compared with group 1 (p < 0.001) and group 3 (p = 0.005). On subdividing group 2 (15-29 years) into "older adolescents" (15-17 years) and "young adults" (18-29 years), post-HTx survival was similar between the two subgroups (p = 0.353). In conclusion, older adolescents and young adults, both, have similarly poor post-HTx survival when BTT with a VAD compared with other age groups. These groups are generally categorized into different broad pediatric and adult age groups; however, these similarities should be carefully considered when formulating treatment protocols for older adolescents and young adults. PMID- 28991811 TI - Vertical Maxillary Measurements using a Virtual External Reference Point in Orthognathic Surgery: Technical Innovation. AB - It is extremely important to achieve vertical position of the upper jaw in orthognathic surgery. A common method used is measuring distances at surgery using external reference points. Unfortunately, surgeons have been making mistakes when calculating the goal distance of our external reference systems. A possible explanation is that when the author measure the baseline and goal vertical distances, the author usually do not consider the variations produced by the triangulation effect generated due the horizontal or/and transverse movements of the maxilla. A method is proposed to fix this phenomenon in an easy way through the virtual customization of the ERP in computer-assisted surgical simulation. The technique entails creating, in the planning software, the same reference system one will use at surgery. In this virtual system, one measures the difference between the baseline and target distances, and then uses them at surgery. PMID- 28991813 TI - Using Discrete-Event Simulation to Promote Quality Improvement and Efficiency in a Radiation Oncology Treatment Center. AB - BACKGROUND: To meet demand for radiation oncology services and ensure patient centered safe care, management in an academic radiation oncology department initiated quality improvement efforts using discrete-event simulation (DES). Although the long-term goal was testing and deploying solutions, the primary aim at the outset was characterizing and validating a computer simulation model of existing operations to identify targets for improvement. METHODS: The adoption and validation of a DES model of processes and procedures affecting patient flow and satisfaction, employee experience, and efficiency were undertaken in 2012 2013. Multiple sources were tapped for data, including direct observation, equipment logs, timekeeping, and electronic health records. RESULTS: During their treatment visits, patients averaged 50.4 minutes in the treatment center, of which 38% was spent in the treatment room. Patients with appointments between 10 AM and 2 PM experienced the longest delays before entering the treatment room, and those in the clinic in the day's first and last hours, the shortest (<5 minutes). Despite staffed for 14.5 hours daily, the clinic registered only 20% of patients after 2:30 PM. Utilization of equipment averaged 58%, and utilization of staff, 56%. CONCLUSION: The DES modeling quantified operations, identifying evidence-based targets for next-phase remediation and providing data to justify initiatives. PMID- 28991814 TI - Management of Traumatic Brain Injury in the Emergency Department: Guideline Adherence and Patient Safety. AB - BACKGROUND: Traumatic brain injury is a common reason not only for emergency visits worldwide but also for significant morbidity and mortality. Several clinical guidelines exist but adherence is generally low. AIM: To study attitudes toward computed tomography of the head among emergency department Change to physicians throughout the article who manage patients with trauma to the head and doctors' adherence to guidelines. METHODS: Quantitative questionnaire study with questionnaires collected over 3 months before introduction of new guidelines. After introduction, intermission of 8 months passed when information and education were given. Thereafter, questionnaires were collected for another 3 months. RESULTS: A total of 694 patients were registered at the emergency department. A total of 161 questionnaires were analyzed; 50.9% did not use guidelines, 39% before intermission, and 60.5% after. When Canadian CT Head Rule was applied, 30.4% of patients with no loss of consciousness were referred to computed tomography, violating guideline recommendation. CONCLUSION: Guidelines are designed to improve performance but are not always applied correctly or as frequently as intended. Information and education did not increase guideline adherence. To improve guideline adherence, more innovative measures than formal guidelines must be undertaken. To find out what these measures are, we suggest qualitative studies to elucidate interventions that will have bigger impact on performance. PMID- 28991812 TI - The Affordable Care Act and Its Effects on Physician Leadership: A Qualitative Systematic Review. AB - OBJECTIVES: The Affordable Care Act (ACA) shifted the focus in medical care from quantity to quality. This qualitative systematic review aimed to determine the key skills necessary for effective physician leaders after the implementation of the ACA, and to compare them with key skills identified prior to its implementation. METHODS: A qualitative systematic review was conducted. A systematic literature search on leadership skills for physicians returned 26 articles published between 2009 and 2016. Thematic analysis was used to categorize the data presented in each article. The results from the thematic analysis were then compared with a similar article published before the implementation of the ACA. RESULTS: Teamwork and team-building, communication, and self-awareness skills were mentioned most often. The percentage of articles mentioning teamwork and team-building skills (61.5%) was significantly greater than the percentage (25%) reported before the implementation of the ACA (P <= .04). CONCLUSION: With the shift toward quality of patient care, health care workers at all levels should strive to work as a team to provide the best quality of care at all stages of patient care. PMID- 28991815 TI - Gap Between Clinical Practice and Guidelines: A National Survey of the Knowledge of Recommended Heart Failure Guidelines Among Chinese Physicians. AB - OBJECTIVE: We investigated the current level of knowledge of Chinese heart failure (HF) guidelines among physicians, as a reference for the promotion and transformation of HF knowledge. METHODS AND RESULTS: Physicians from 88 hospitals in 27 provinces of China completed our survey between July and December 2014. The questions covered the main points included in the Chinese HF diagnosis and treatment guidelines (2014). A total of 2146 physicians, aged 20 to 62 years (35.6 +/- 7.6 years), completed the survey. The correctness rate of their answers to the 15 multiple-choice questions in the HF questionnaire was generally low (mean 32.6%). The mean correctness rate for 10 blank-filling questions about the target doses of angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, and beta-blockers was 42.5%. On the basis of their responses, physicians whose knowledge of the guidelines was "excellent," "good," "medium," and "bad" accounted for 1.1%, 11.4%, 14.2%, and 73.4%, respectively. Physicians who possessed a higher level of qualifications had significantly greater awareness of HF guidelines than those with relatively low qualifications (P < .001). A statistically significant association was found between hospital level and adherence to treatment guidelines (P < .001). A significant difference was also observed among physicians in different practice scopes (P < .001). CONCLUSIONS: The survey found an obvious deficiency in physicians' mastery of fundamental knowledge about HF. There is a need to improve physicians' education about HF in China. PMID- 28991816 TI - Does Hospital Size Affect Patient Satisfaction? AB - BACKGROUND: Centers for Medicare & Medicaid Services reimbursement is now contingent on quality measures such as patient satisfaction as determined by Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS). In providing patient-centered care that is guided by patient satisfaction measures, it is critical to understand system-level factors that may influence how patients assess their care experiences. One important system-level influence to consider is hospital size. METHODS: HCAHPS scores, number of hospital beds, and nursing magnet status were obtained from publically available Hospital Compare, American Hospital Directory, and Magnet Hospitals Web sites, respectively. An aggregate score for patient satisfaction was created across all domains of the HCAHPS. Multilevel regression modeling was performed to examine the associations between hospital size and HCAHPS aggregate and individual dimensions. RESULTS: Hospital size was significantly associated with patient satisfaction such that larger size was associated with lower satisfaction (beta = -.312, P < .001). Hospital size was most strongly associated with less patient satisfaction on the following HCAHPS items: "receiving help as soon as needed" (beta = -.441, P < .001), "room and bathroom cleanliness" (beta = -.286, P < .001), and doctor communication (beta = -.213, P < .001), whereas nurse communication (beta = .194, P < .001) was the one modifiable dimension that was associated with more favorable ratings in larger hospitals. Magnet nursing designation was significantly associated with larger hospital size (P < .001). CONCLUSION: Patient satisfaction scores may be lower in large hospitals because of patients' perceptions of hospital cleanliness, receiving help on time, and doctor communication. Focusing on improving these factors may improve patient satisfaction scores for larger hospitals. PMID- 28991817 TI - The Moderating Role of Hospital Size on the Relationship Between Patient Experience and Patient Safety. AB - OBJECTIVES: Previous examinations of the relationship between patient experience and patient safety initiatives find that higher patient experience evaluations correspond to reduced incidence of adverse events. Little is known, however, about the impact of hospital organizational characteristics on this relationship. The purpose of this study is to examine the degree to which hospital size moderates the relationship between patient experience and patient safety. METHODS: A lagged cross-sectional ordinary least squares regression tests a hypothesis of a diminishing effect of hospital size on the relationship between patient evaluations of their interpersonal care experience and hospital's central line associated bloodstream infection (CLABSI) is tested on a sample of 1740 US hospitals using data compiled from Hospital Compare and the American Hospital Association. RESULTS: The results find that the magnitude of the relationship between patient experience and patient safety initiatives is diminished as hospital size increases and suggest that care providers' ability to deliver care in a manner that is simultaneously responsive to individual patient needs and preferences and reliable in its avoidance of adverse events is influenced by hospital size. An additional fractional logit is presented, which accounts for restrictions in the dependent variable further support study findings. PMID- 28991818 TI - From Clinic to Community: A Framework for Providing Diabetes Prevention Services That Cross the Care Continuum. PMID- 28991822 TI - Respiratory Viruses in Invasively Ventilated Critically Ill Patients-A Prospective Multicenter Observational Study. AB - OBJECTIVES: The presence of respiratory viruses and the association with outcomes were assessed in invasively ventilated ICU patients, stratified by admission diagnosis. DESIGN: Prospective observational study. SETTING: Five ICUs in the Netherlands. PATIENTS: Between September 1, 2013, and April 30, 2014, 1,407 acutely admitted and invasively ventilated patients were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Nasopharyngeal swabs and tracheobronchial aspirates were collected upon intubation and tested for 14 respiratory viruses. Out of 1,407 patients, 156 were admitted because of a severe acute respiratory infection and 1,251 for other reasons (non-severe acute respiratory infection). Respiratory viruses were detected in 28.8% of severe acute respiratory infection patients and 17.0% in non-severe acute respiratory infection (p < 0.001). In one third, viruses were exclusively detected in tracheobronchial aspirates. Rhinovirus and human metapneumovirus were more prevalent in severe acute respiratory infection patients (9.6% and 2.6% vs 4.5 and 0.2%; p = 0.006 and p < 0.001). In both groups, there were no associations between the presence of viruses and the number of ICU-free days at day 28, crude mortality, and mortality in multivariate regression analyses. CONCLUSIONS: Respiratory viruses are frequently detected in acutely admitted and invasively ventilated patients. Rhinovirus and human metapneumovirus are more frequently found in severe acute respiratory infection patients. Detection of respiratory viruses is not associated with worse clinically relevant outcomes in the studied cohort of patients. PMID- 28991824 TI - The beta-Blocker Esmolol Restores the Vascular Waterfall Phenomenon After Acute Endotoxemia. AB - BACKGROUND: A vascular waterfall occurs when the critical closing pressure is greater than the mean systemic filling pressure. Because the waterfall phenomenon likely exists in the microcirculation, beta1-receptor blockers such as esmolol could have some effect on microcirculation and vascular waterfall. OBJECTIVES: To determine whether a vascular waterfall exists during septic shock and to assess the effects of vasopressors and beta-blockers on vascular waterfall. DESIGN: Sixteen mongrel dogs were mounted with ultrasonic flow probes to measure renal blood flow. The hemodynamic variables of 16 animals were measured at baseline, after induction of acute endotoxemia; then, they underwent volume expansion, and norepinephrine was used to achieve baseline. After achieving septic myocardial depression, the animals were randomly divided into two groups (esmolol vs control groups) after reaching septic myocardial depression. MEASUREMENTS AND MAIN RESULTS: There was a pressure gap of 41.9 +/- 13.9 mm Hg between the arterial critical closing pressure and the mean systemic filling pressure, indicating that a vascular waterfall was present under baseline conditions. Endotoxemia caused a decrease in cardiac output, mean arterial pressure, and critical closing pressure. Endotoxemia also caused the vascular waterfall to disappear. Neither volume expansion nor norepinephrine had any effect on the vascular waterfall. Esmolol infusion restored the vascular waterfall effect following endotoxemia and resuscitation. The 24-hour survival was 75% in the esmolol group versus 12.5% in controls (p = 0.041). CONCLUSIONS: Vascular pressure gradients in renal vasculature suggest the presence of a vascular waterfall at baseline. Although this phenomenon disappeared in endotoxemic dogs, it could be restored with beta blocker therapy (esmolol). PMID- 28991823 TI - Mortality Benefit of Recombinant Human Interleukin-1 Receptor Antagonist for Sepsis Varies by Initial Interleukin-1 Receptor Antagonist Plasma Concentration. AB - OBJECTIVE: Plasma interleukin-1 beta may influence sepsis mortality, yet recombinant human interleukin-1 receptor antagonist did not reduce mortality in randomized trials. We tested for heterogeneity in the treatment effect of recombinant human interleukin-1 receptor antagonist by baseline plasma interleukin-1 beta or interleukin-1 receptor antagonist concentration. DESIGN: Retrospective subgroup analysis of randomized controlled trial. SETTING: Multicenter North American and European clinical trial. PATIENTS: Five hundred twenty-nine subjects with sepsis and hypotension or hypoperfusion, representing 59% of the original trial population. INTERVENTIONS: Random assignment of placebo or recombinant human interleukin-1 receptor antagonist * 72 hours. MEASUREMENTS AND MAIN RESULTS: We measured prerandomization plasma interleukin-1 beta and interleukin-1 receptor antagonist and tested for statistical interaction between recombinant human interleukin-1 receptor antagonist treatment and baseline plasma interleukin-1 receptor antagonist or interleukin-1 beta concentration on 28-day mortality. There was significant heterogeneity in the effect of recombinant human interleukin-1 receptor antagonist treatment by plasma interleukin-1 receptor antagonist concentration whether plasma interleukin-1 receptor antagonist was divided into deciles (interaction p = 0.046) or dichotomized (interaction p = 0.028). Interaction remained present across different predicted mortality levels. Among subjects with baseline plasma interleukin-1 receptor antagonist above 2,071 pg/mL (n = 283), recombinant human interleukin-1 receptor antagonist therapy reduced adjusted mortality from 45.4% to 34.3% (adjusted risk difference, -0.12; 95% CI, -0.23 to -0.01), p = 0.044. Mortality in subjects with plasma interleukin 1 receptor antagonist below 2,071 pg/mL was not reduced by recombinant human interleukin-1 receptor antagonist (adjusted risk difference, +0.07; 95% CI, -0.04 to +0.17), p = 0.230. Interaction between plasma interleukin-1 beta concentration and recombinant human interleukin-1 receptor antagonist treatment was not statistically significant. CONCLUSIONS: We report a heterogeneous effect of recombinant human interleukin-1 receptor antagonist on 28-day sepsis mortality that is potentially predictable by plasma interleukin-1 receptor antagonist in one trial. A precision clinical trial of recombinant human interleukin-1 receptor antagonist targeted to septic patients with high plasma interleukin-1 receptor antagonist may be worthy of consideration. PMID- 28991825 TI - Evaluation of Vasopressin for Septic Shock in Patients on Chronic Renin Angiotensin-Aldosterone System Inhibitors. AB - OBJECTIVES: To compare the hemodynamic response in septic shock patients receiving vasopressin who were on chronic renin-angiotensin-aldosterone system inhibitor therapy with those who were not. DESIGN: Single-center, retrospective cohort study. SETTING: Medical and surgical ICUs at a 1,100-bed academic medical center. PATIENTS: Medical and surgical ICU patients with septic shock who received vasopressin infusion added to at least one concomitant vasopressor agent between January 2014 and December 2015, then divided into two cohorts: 1) patients who were on chronic renin-angiotensin-aldosterone system inhibitor therapy as outpatients and 2) patients who were not on chronic renin-angiotensin aldosterone system inhibitor therapy as outpatients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure at 6 hours was 72.2 mm Hg in the renin-angiotensin-aldosterone system inhibitor group versus 69.7 mm Hg in the non-renin-angiotensin-aldosterone system inhibitor group (p = 0.298). There was no difference in mean arterial pressure at 1, 24, or 48 hours between groups. Total concomitant vasopressor requirements, based on norepinephrine equivalents excluding vasopressin, were significantly lower at 24 hours in the renin angiotensin-aldosterone system inhibitor group versus the non-renin-angiotensin aldosterone system inhibitor group (10.7 vs 18.1 ug/min, respectively; p = 0.007), but no significant differences were seen at the other time points assessed. There were no significant differences in ICU or hospital length of stay or mortality. CONCLUSIONS: There was no significant difference in the primary outcome of 6-hour mean arterial pressure in septic shock patients receiving vasopressin who were on chronic renin-angiotensin-aldosterone system inhibitor therapy versus those receiving vasopressin who were not on chronic renin angiotensin-aldosterone system inhibitor therapy. Renin-angiotensin-aldosterone system inhibitor patients had lower total concomitant vasopressor requirements at 24 hours compared with non-renin-angiotensin-aldosterone system inhibitor patients. PMID- 28991826 TI - Relationship of at Admission Lactate, Unmeasured Anions, and Chloride to the Outcome of Critically Ill Patients. AB - OBJECTIVES: To investigate the association between the concentration of the causative anions responsible for the main types of metabolic acidosis and the outcome. DESIGN: Prospective observational study. SETTING: Teaching ICU. PATIENTS: All patients admitted from January 2006 to December 2014. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Four thousand nine hundred one patients were admitted throughout the study period; 1,609 met criteria for metabolic acidosis and 145 had normal acid-base values. The association between at admission lactate, unmeasured anions, and chloride concentration with outcome was assessed by multivariate analysis in the whole cohort and in patients with metabolic acidosis. We also compared the mortality of patients with lactic, unmeasured anions, and hyperchloremic metabolic acidosis with that of patients without acid-base disorders. In the whole population, increased lactate and unmeasured anions were independently associated with increased mortality, even after adjusting for potential confounders (odds ratio [95% CI], 1.14 (1.08-1.20); p < 0.0001 and 1.04 (1.02-1.06); p < 0.0001, respectively). In patients with metabolic acidosis, the results were similar. Patients with lactic and unmeasured anions acidosis, but not those with hyperchloremic acidosis, had an increased mortality compared to patients without alterations (17.7%, 12.7%, 4.9%, and 5.8%, respectively; p < 0.05). CONCLUSIONS: In this large cohort of critically ill patients, increased concentrations of lactate and unmeasured anions, but not chloride, were associated with increased mortality. In addition, increased unmeasured anions were the leading cause of metabolic acidosis. PMID- 28991827 TI - Sepsis Survivors Admitted to Skilled Nursing Facilities: Cognitive Impairment, Activities of Daily Living Dependence, and Survival. AB - OBJECTIVE: Severe sepsis survivors frequently experience cognitive and physical functional impairment. The degree of impairment and its association with mortality is understudied, particularly among those discharged to a skilled nursing facility. Our objective was to quantify the cognitive and physical impairment among severe sepsis survivors discharged to a skilled nursing facility and to investigate the relationship between impairment and long-term mortality. DESIGN: Retrospective cohort study. SETTING: United States. SUBJECTS: Random 5% sample of Medicare patients discharged following severe sepsis hospitalization, 2005-2009 (n = 135,370). MEASUREMENT AND MAIN RESULTS: Medicare data were linked with the Minimum Data Set; Minimum Data Set-Cognition Scale was used to assess cognitive function, and the Minimum Data Set activities of daily living hierarchical scale was used to assess functional dependence. Associations were evaluated using multivariable logistic regression, Kaplan-Meier curves, and Cox proportional hazards regression. Of 66,540 beneficiaries admitted to a skilled nursing facility following severe sepsis, 34% had severe or very severe cognitive impairment, and 72.5% had maximal, dependence, or total dependence in activities of daily living. Median survival was 19.4 months for those discharged to a skilled nursing facility without having been in a skilled nursing facility in the preceding 1 year and 10.4 months for those discharged to a skilled nursing facility who had spent time in a skilled nursing facility in the prior year. The adjusted hazard ratio for death was 3.1 for those with very severe cognitive impairment relative to those who were cognitively intact (95% CI, 2.9-3.2; p < 0.001) and 4.3 for those with "total dependence" in activities of daily livings relative to those who were independent (95% CI, 3.8-5.0; p < 0.001). CONCLUSIONS: Discharge to a skilled nursing facility following severe sepsis hospitalization among Medicare beneficiaries was associated with shorter survival, and cognitive impairment and activities of daily living dependence were each strongly associated with shortened survival. These findings can inform decision-making by patients and physicians and underscores high palliative care needs among sepsis survivors discharged to skilled nursing facility. PMID- 28991828 TI - Pediatric Sepsis Endotypes Among Adults With Sepsis. AB - OBJECTIVES: Recent transcriptomic studies describe two subgroups of adults with sepsis differentiated by a sepsis response signature. The implied biology and related clinical associations are comparable with recently reported pediatric sepsis endotypes, labeled "A" and "B." We classified adults with sepsis using the pediatric endotyping strategy and the sepsis response signature and determined how endotype assignment, sepsis response signature membership, and age interact with respect to mortality. DESIGN: Retrospective analysis of publically available transcriptomic data representing critically ill adults with sepsis from which the sepsis response signature groups were derived and validated. SETTING: Multiple ICUs. PATIENTS: Adults with sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Transcriptomic data were conormalized into a single dataset yielding 549 unique cases with sepsis response signature assignments. Each subject was assigned to endotype A or B using the expression data for the 100 endotyping genes. There were 163 subjects (30%) assigned to endotype A and 386 to endotype B. There was a weak, positive correlation between endotype assignment and sepsis response signature membership. Mortality rates were similar between patients assigned endotype A and those assigned endotype B. A multivariable logistic regression model fit to endotype assignment, sepsis response signature membership, age, and the respective two-way interactions revealed that endotype A, sepsis response signature 1 membership, older age, and the interactions between them were associated with mortality. Subjects coassigned to endotype A, and sepsis response signature 1 had the highest mortality. CONCLUSIONS: Combining the pediatric endotyping strategy with sepsis response signature membership might provide complementary, age-dependent, biological, and prognostic information. PMID- 28991829 TI - Sepsis Reduces Bone Strength Before Morphologic Changes Are Identifiable. AB - OBJECTIVES: Survivors of critical illness have an increased prevalence of bone fractures. However, early changes in bone strength, and their relationship to structural changes, have not been described. We aimed to characterize early changes in bone functional properties in critical illness and their relationship to changes in bone structure, using a sepsis rodent model. DESIGN: Experimental study. SETTING: Animal research laboratory. SUBJECTS: Adult Sprague-Dawley rats. INTERVENTIONS: Forty Sprague-Dawley rats were randomized to cecal ligation and puncture or sham surgery. Twenty rodents (10 cecal ligation and puncture, 10 sham) were killed at 24 hours, and 20 more at 96 hours. MEASUREMENTS AND MAIN RESULTS: Femoral bones were harvested for strength testing, microCT imaging, histologic analysis, and multifrequency scanning probe microscopy. Fracture loads at the femoral neck were significantly reduced for cecal ligation and puncture exposed rodents at 24 hours (83.39 +/- 10.1 vs 103.1 +/- 17.6 N; p = 0.014) and 96 hours (81.60 +/- 14.2 vs 95.66 +/- 14.3 N; p = 0.047). Using multifrequency scanning probe microscopy, collagen elastic modulus was lower in cecal ligation and puncture-exposed rats at 24 hours (1.37 +/- 0.2 vs 6.13 +/- 0.3 GPa; p = 0.001) and 96 hours (5.57 +/- 0.5 vs 6.13 +/- 0.3 GPa; p = 0.006). Bone mineral elastic modulus was similar at 24 hours but reduced in cecal ligation and puncture-exposed rodents at 96 hours (75.34 +/- 13.2 vs 134.4 +/- 8.2 GPa; p < 0.001). There were no bone architectural or bone mineral density differences by microCT. Similarly, histologic analysis demonstrated no difference in collagen and elastin staining, and C-X-C chemokine receptor type 4, nuclear factor kappa beta, and tartrate-resistant acid phosphatase immunostaining. CONCLUSIONS: In a rodent sepsis model, trabecular bone strength is functionally reduced within 24 hours and is associated with a reduction in collagen and mineral elastic modulus. This is likely to be the result of altered biomechanical properties, rather than increased bone mineral turnover. These data offer both mechanistic insights and may potentially guide development of therapeutic interventions. PMID- 28991831 TI - Extracorporeal Membrane Oxygenation Is Not First-Line Therapy for the Acute Respiratory Distress Syndrome. PMID- 28991830 TI - Development and Validation of an Empiric Tool to Predict Favorable Neurologic Outcomes Among PICU Patients. AB - OBJECTIVES: To create a novel tool to predict favorable neurologic outcomes during ICU stay among children with critical illness. DESIGN: Logistic regression models using adaptive lasso methodology were used to identify independent factors associated with favorable neurologic outcomes. A mixed effects logistic regression model was used to create the final prediction model including all predictors selected from the lasso model. Model validation was performed using a 10-fold internal cross-validation approach. SETTING: Virtual Pediatric Systems (VPS, LLC, Los Angeles, CA) database. PATIENTS: Patients less than 18 years old admitted to one of the participating ICUs in the Virtual Pediatric Systems database were included (2009-2015). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 160,570 patients from 90 hospitals qualified for inclusion. Of these, 1,675 patients (1.04%) were associated with a decline in Pediatric Cerebral Performance Category scale by at least 2 between ICU admission and ICU discharge (unfavorable neurologic outcome). The independent factors associated with unfavorable neurologic outcome included higher weight at ICU admission, higher Pediatric Index of Morality-2 score at ICU admission, cardiac arrest, stroke, seizures, head/nonhead trauma, use of conventional mechanical ventilation and high-frequency oscillatory ventilation, prolonged hospital length of ICU stay, and prolonged use of mechanical ventilation. The presence of chromosomal anomaly, cardiac surgery, and utilization of nitric oxide were associated with favorable neurologic outcome. The final online prediction tool can be accessed at https://soipredictiontool.shinyapps.io/GNOScore/. Our model predicted 139,688 patients with favorable neurologic outcomes in an internal validation sample when the observed number of patients with favorable neurologic outcomes was among 139,591 patients. The area under the receiver operating curve for the validation model was 0.90. CONCLUSIONS: This proposed prediction tool encompasses 20 risk factors into one probability to predict favorable neurologic outcome during ICU stay among children with critical illness. Future studies should seek external validation and improved discrimination of this prediction tool. PMID- 28991832 TI - Adaptation of a Biomarker-Based Sepsis Mortality Risk Stratification Tool for Pediatric Acute Respiratory Distress Syndrome. AB - OBJECTIVES: The original Pediatric Sepsis Biomarker Risk Model and revised (Pediatric Sepsis Biomarker Risk Model-II) biomarker-based risk prediction models have demonstrated utility for estimating baseline 28-day mortality risk in pediatric sepsis. Given the paucity of prediction tools in pediatric acute respiratory distress syndrome, and given the overlapping pathophysiology between sepsis and acute respiratory distress syndrome, we tested the utility of Pediatric Sepsis Biomarker Risk Model and Pediatric Sepsis Biomarker Risk Model II for mortality prediction in a cohort of pediatric acute respiratory distress syndrome, with an a priori plan to revise the model if these existing models performed poorly. DESIGN: Prospective observational cohort study. SETTING: University affiliated PICU. PATIENTS: Mechanically ventilated children with acute respiratory distress syndrome. INTERVENTIONS: Blood collection within 24 hours of acute respiratory distress syndrome onset and biomarker measurements. MEASUREMENTS AND MAIN RESULTS: In 152 children with acute respiratory distress syndrome, Pediatric Sepsis Biomarker Risk Model performed poorly and Pediatric Sepsis Biomarker Risk Model-II performed modestly (areas under receiver operating characteristic curve of 0.61 and 0.76, respectively). Therefore, we randomly selected 80% of the cohort (n = 122) to rederive a risk prediction model for pediatric acute respiratory distress syndrome. We used classification and regression tree methodology, considering the Pediatric Sepsis Biomarker Risk Model biomarkers in addition to variables relevant to acute respiratory distress syndrome. The final model was comprised of three biomarkers and age, and more accurately estimated baseline mortality risk (area under receiver operating characteristic curve 0.85, p < 0.001 and p = 0.053 compared with Pediatric Sepsis Biomarker Risk Model and Pediatric Sepsis Biomarker Risk Model-II, respectively). The model was tested in the remaining 20% of subjects (n = 30) and demonstrated similar test characteristics. CONCLUSIONS: A validated, biomarker-based risk stratification tool designed for pediatric sepsis was adapted for use in pediatric acute respiratory distress syndrome. The newly derived Pediatric Acute Respiratory Distress Syndrome Biomarker Risk Model demonstrates good test characteristics internally and requires external validation in a larger cohort. Tools such as Pediatric Acute Respiratory Distress Syndrome Biomarker Risk Model have the potential to provide improved risk stratification and prognostic enrichment for future trials in pediatric acute respiratory distress syndrome. PMID- 28991833 TI - Optical Coherence Tomography Angiography Vessel Density Measurements in Eyes With Primary Open-Angle Glaucoma and Disc Hemorrhage. AB - PURPOSE: To compare the vessel density measurements of optic nerve head, peripapillary and macular regions in severity-matched primary open-angle glaucoma (POAG) eyes with and without disc hemorrhage (DH) using optical coherence tomography (OCT) angiography, and to compare their diagnostic abilities with that of the rim area, retinal nerve fiber layer and the ganglion cell complex thickness measurements on OCT. METHODS: In a cross-sectional study, 66 eyes of 46 control subjects, 34 eyes of 33 POAG patients with DH (median mean deviation=-3.7 dB) and 63 eyes of 43 POAG patients without DH (median mean deviation=-3.8 dB) underwent imaging with spectral domain OCT. Area under receiver operating characteristic curves (AUC) and 5sensitivities at 90% specificity of vessel density and structural measurements in POAG eyes with DH were compared with those in POAG eyes without DH. RESULTS: Most of the vessel density and structural measurements were similar (P>0.05) in POAG eyes with and without DH. Whole enface vessel density of the disc scan and inferotemporal peripapillary vessel density showed the best AUC and sensitivity at 90% specificity both in POAG eyes with DH (0.82, 56% and 0.75, 59%) and without DH (0.91, 73% and 0.83, 67%). AUCs and sensitivities of vessel density and structural measurements of POAG eyes with and without DH were statistically similar (P>0.05). CONCLUSIONS: OCT angiography measured vessel densities and their diagnostic abilities in POAG eyes with and without DH were similar. This suggests that the cause of DH in POAG is unlikely to be vascular abnormality. PMID- 28991834 TI - Spontaneous Retinal Venous Pulsation in Unilateral Primary Open-angle Glaucoma With Low Intraocular Pressure. AB - PURPOSE: The aim of this study was to investigate the presence of spontaneous retinal venous pulsation (SVP) in patients with unilateral primary open-angle glaucoma (POAG) and low intraocular pressure (IOP). MATERIALS AND METHODS: The SVP of 93 POAG patients with unilateral glaucoma and untreated IOP of <=21 mm Hg was assessed using the movie tool of a confocal scanning laser ophthalmoscope (Spectralis HRA; Heidelberg Engineering). The frequency of SVP was compared between the glaucomatous and fellow eyes. Intereye differences in the frequency of SVP were assessed using McNemar test. A linear mixed-effect model was used to determine the factors associated with glaucomatous eyes, taking into account clustering of eyes within subjects. RESULTS: Forty-five patients had SVP in both eyes and 15 had SVP in neither eye. Of the remaining 33 patients who showed SVP only in 1 eye, 31 had SVP only in the fellow eye, and 2 had SVP only in the glaucomatous eye. The SVP was significantly less prevalent in glaucomatous eyes (50.5%) than in fellow control eyes (81.7%) (P<0.001). In the linear mixed-effect model, the presence of SVP (P<0.001) and higher untreated IOP (P=0.001) were the significant predictors for glaucoma. CONCLUSIONS: SVP was less frequently found in glaucomatous eyes than healthy fellow eyes in unilateral POAG patients with low IOP. PMID- 28991835 TI - Celiac Disease Diagnosis Without Biopsy: Is a 10* ULN Antitransglutaminase Result Suitable for a Chemiluminescence Method? AB - OBJECTIVES: 2012 European Society of Pediatric Gastroenterology, Hepatology and Nutrition guidelines allow to establish a celiac disease diagnosis without duodenal biopsy in symptomatic pediatric patients with antitissue transglutaminase (anti-tTG) titers >10 times the upper limit of normal. For some years now, new chemiluminescence immunoassays have been made available: it is important to establish the clinical performance of anti-tTG and to determine the cut-off best suited to predict Marsh >=2 to avoid gastrointestinal endoscopy not only in children, but also in the adult population. METHODS: A total of 2565 patients performed duodenal biopsy from July 2012 to September 2016; we selected all the patients who had undergone QUANTA Flash anti-tTG immunoglobulin A (IgA) within -3 months of duodenal biopsy and before the start of gluten-free diet. A total of 827 patients fulfilled the criteria for selection. RESULTS: Using a cut off of 20 chemiluminescent unit (CU; area under the curve: 0.995), sensitivity, specificity, positive, and negative predictive value were 98.2%, 98.4%, 97.9%, and 98.6%, respectively. For the correlation with Marsh >=2, in the pediatric population, positive predictive values (PPV) were 92.1%, 99%, and 100% at 200 CU (10*), 560 CU (28*), and 1000 CU (50*), respectively. In the adult population PPV was 94.2%, 98.2%, and 100% at 200 CU (10*), 350 CU (15*), and 400 CU (20*). CONCLUSIONS: Sensitivity, specificity, positive, and negative predictive value of QUANTA Flash h-tTG IgA were excellent. The cut-off providing an optimized PPV for histological lesions compatible for celiac disease (Marsh >=2) for the QUANTA Flash h-tTG IgA is 350 CU (15*) in adult and 560 CU (28*) in children. PMID- 28991836 TI - Direct Acting Antiviral Treatment Selection in a Child With Hepatitis C Virus Infection and Compensated Cirrhosis. PMID- 28991837 TI - Serum Osteocalcin Levels in Children With Nonalcoholic Fatty Liver Disease. AB - OBJECTIVES: The aim of the study was to investigate the relationship between osteocalcin and nonalcoholic fatty liver disease (NAFLD) in children with obesity. METHOD: 60 obese children with NAFLD were taken as a patient group and 60 obese children and normal liver with matching age, sex, and body mass index were taken as a control group. Anthropometric measurements, abdominal ultrasonography for diagnosis and grading of NAFLD, and laboratory investigations in the form of liver function tests, lipid profile, fasting serum glucose and insulin, and serum osteocalcin levels were done for all children. Patients with NAFLD were further divided into patients with metabolic syndrome (MS) and patients without MS. RESULTS: Age of NAFLD children was (10.55 +/- 2.71), 20 boys and 40 girls, whereas age of children in control group was (10.05 +/- 3.51), 24 boys and 36 girls (P > 0.05). Patients with NAFLD showed significant increase in waist and hip circumference, alanine aminotransferase, alkaline phosphatase, total cholesterol, triglycerides, insulin resistance (IR), fasting serum glucose, and insulin, but lower serum osteocalcin level than control group. Serum osteocalcin level is inversely correlated with waist circumference, triglyceride, liver enzymes, fasting serum insulin, fasting serum glucose, IR, and grades of fatty liver. Increase in alanine aminotransferase, total cholesterol, triglycerides, fasting insulin, and IR went with increase in degree of hepatic steatosis. Serum osteocalcin level <44.5 ng/mL is a good predictor for severity of hepatic steatosis with sensitivity and specificity of 80%. CONCLUSIONS: Osteocalcin plays an important role in glucose and lipid metabolism for protection against NAFLD occurrence and progression. Moreover, it could be a useful marker for progression of NAFLD in children with obesity. PMID- 28991838 TI - The Relation Between Malnutrition and the Exocrine Pancreas: A Systematic Review. AB - OBJECTIVE: The relation between malnutrition and exocrine pancreatic insufficiency (EPI) has been described previously, but it is unclear if malnutrition leads to EPI or vice versa. We systematically synthesized current evidence evaluating the association between malnutrition and EPI in children. METHODS: Pubmed, Embase, and Cochrane databases were searched from inception until February 2017. We included cohort or case-controlled studies in children reporting on prevalence or incidence of EPI and malnutrition. Data generation was performed independently by 2 authors. Quality was assessed by using quality assessment tools from the National Heart, Lung, and Blood Institute. RESULTS: Nineteen studies were divided into 2 groups: 10 studies showing EPI leading to malnutrition, and 9 studies showing malnutrition leading to EPI. Because of heterogeneity in design, definitions, and outcome measures, pooling of results was impossible. Quality was good in 4 of 19 studies. Pancreatic insufficiency was linked to decreased nutritional status in 8 of 10 articles, although this link was not specified properly in most articles. In malnourished children, improvement was seen in pancreatic function in 7 of 9 articles after nutritional rehabilitation. The link between the 2 was not further specified. Heterogeneity exists with respect to definitions, outcome measures, and study design. CONCLUSIONS: There is sufficient evidence for an association between EPI and malnutrition. We could not confirm whether there is a correlation or causality between EPI or malnutrition. It was therefore not possible to draw firm conclusions from this systematic review on underlying pathophysiological mechanisms between EPI and malnutrition. More observational clinical trials are crucially needed. PMID- 28991839 TI - Fecal Microbial Transplant In Children With Ulcerative Colitis: A Randomized, Double-Blinded, Placebo-Controlled Pilot Study: Retracted. PMID- 28991840 TI - Granulomatous Upper Gastrointestinal Inflammation in Pediatric Ulcerative Colitis. AB - OBJECTIVES: Differentiating ulcerative colitis (UC) and Crohn disease (CD) can be clinically challenging, especially in children. Granulomatous inflammation has traditionally been attributed to CD. Crypt-associated giant cells and granulomas, however, have been observed in colonic biopsies of patients with UC. This phenomenon has not been described in the upper gastrointestinal (UGI) tract with UC. METHODS: Seven pediatric patients with UC with granulomatous UGI (gUGI) lesions were identified. Diagnosis of UC was based on symptoms, clinical course, laboratory results, imaging, and endoscopy. We compared the gUGI patients to a large cohort of pediatric patients with UC (n = 149). RESULTS: All fully evaluated cases were associated with bloody diarrhea and moderate to severe pancolitis. Gastric and/or duodenal biopsies demonstrated giant cells or granulomas near gland destruction. Small bowel imaging did not reveal any involvement. The majority of cases responded to standard medical therapies, except for 2 patients (28.6%) who required total colectomy. Acute severe, refractory colitis (ie, colectomy within 1 month of presentation) was significantly more common in the gUGI group than the large pediatric UC group (28.6% vs 1.3%, Fisher exact P = 0.01). CONCLUSIONS: This is the first report of pediatric UC-associated granulomatous inflammation in the UGI tract. We speculate that these lesions represent extracolonic manifestations of intense colonic disease. These atypical findings expand the diagnostic considerations that should be incorporated during the differentiation between UC and CD in the pediatric age group. PMID- 28991841 TI - Leading by Example: Role Modeling Resilience Helps Our Learners and Ourselves. AB - The issues of burnout and its consequences are some of the most prevalent topics in conversations about the practice of medicine today. Many reports have focused on the contributors that fuel this epidemic, but the time has come to begin to focus on solutions. Prominent national efforts, including a National Academy of Medicine collaborative task force and the 2017 Accreditation Council for Graduate Medical Education common program requirements' focus on wellness, are presenting opportunities for academic medicine faculty to take the lead in turning this tide. While solutions to the burnout crisis are complex, the foundations of improving this epidemic lie in restoring a sense of purpose and balance in the lives of those who work in academic medicine. The inherent value of academic medicine to improve others' lives through patient care, the advancement of knowledge, and the education of the next generation is a unique opportunity that many other professions do not share. On the best days, academic medicine faculty must remember to look for that joy and to express it to learners, and, on the worst, they must demonstrate to learners how to practice self-care and how to create personal resilience. By taking on the role of becoming resilient, faculty start to foster a culture of well-being rather than burnout and can begin to find solutions instead of continuing to describe the problem. PMID- 28991842 TI - Medical School Factors That Prepare Students to Become Leaders in Medicine. AB - PURPOSE: To identify medical school factors graduates in major leadership positions perceive as contributing to their leadership development. METHOD: Using a phenomenological, qualitative approach, in August-November 2015 the authors conducted semistructured interviews with 48 medical leaders who were 1976-1999 baccalaureate-MD graduates of the University of Missouri-Kansas City School of Medicine (UMKC). At UMKC, they participated in longitudinal learning communities, the centerpiece for learning professional values and behaviors plus clinical skills, knowledge, and judgment, but received no formal leadership instruction. The authors subjected interview comments to directed, largely qualitative content analysis with iterative coding cycles. RESULTS: Most graduates said their experiences and the people at UMKC positively influenced their leadership growth. Medical school factors that emerged as contributing to that growth were the longitudinal learning communities including docents, junior-senior partners, and team experiences; expectations set for students to achieve; a clinically oriented but integrated curriculum; admission policies seeking students with academic and nonacademic qualifications; supportive student-student and student-faculty relationships; and a positive overall learning environment. Graduates viewed a combination of factors as best preparing them for leadership and excellence in clinical medicine; together these factors enabled them to assume leadership opportunities after graduation. CONCLUSIONS: This study adds medical leaders' perspective to the leadership development literature and offers guidance from theory and practice for medical schools to consider in shaping leadership education: Namely, informal leadership preparation coupled with extensive longitudinal clinical education in a nurturing, authentic environment can develop students effectively for leadership in medicine. PMID- 28991843 TI - Beyond "Dr. Feel-Good": A Role for the Humanities in Medical Education. AB - Although educators embrace the values that are nominally included in the idea of "the art and science of medicine," the arts and humanities have remained at the edges of medical education. One reason for this exile is the overwhelming emphasis in the curriculum on biomedical science over the social sciences and humanities. Other causes are self-inflicted-a frequent lack of theoretical rigor in the design of educational offerings and, more important, no clear answer to the question of how the humanities can make better physicians. A common justification for including the arts and humanities in medical education-that spending time with literature, music, and the visual arts contributes to student and faculty reflection and well-being-is compelling; however, it risks further marginalizing the field as a soft, feel-good supplement to training.In this Invited Commentary, the author proposes several unique ways in which the arts and humanities contribute to the development of physicians who practice with excellence, compassion, and justice.These ways include disrupting taken-for granted beliefs and assumptions; introducing a pause in perceiving, thinking, and acting; encouraging engagement with complexity and ambiguity; seeing past the surface to historical and societal influences and causes; and encouraging an awareness of the multiple, unique voices and perspectives of patients. Ultimately, the humanities prompt awareness of the space in which physicians care for human beings in their moments of greatest need and bear witness to fundamental changes in their patients and in themselves. PMID- 28991844 TI - Criterion-Based Assessment in a Norm-Based World: How Can We Move Past Grades? AB - In the United States, the medical education community has begun a shift from the Flexnerian time-based model to a competency-based medical education model. The graduate medical education (GME) community is substantially farther along in this transition than is the undergraduate medical education (UME) community.GME has largely adopted the use of competencies and their attendant milestones and increasingly is employing the framework of entrustable professional activities (EPAs) to assess trainee competence. The UME community faces several challenges to successfully navigating a similar transition. First is the reliance on norm based reference standards in the UME-GME transition, comparing students' performance versus their peers' with grades, United States Medical Licensing Examination Step 1 and Step 2 score interpretation, and the structured Medical School Performance Evaluation, or dean's letter. Second is the reliance on proxy assessments rather than direct observation of learners. Third is the emphasis on summative rather than formative assessments.Educators have overcome a major barrier to change by establishing UME outcomes assessment criteria with the advent and general acceptance of the physician competency reference set and the Core EPAs for Entering Residency in UME. Now is the time for the hard work of developing assessments steeped in direct observation that can be accepted by learners and faculty across the educational continuum and can be shown to predict clinical performance in a much more meaningful way than the current measures of grades and examinations. The acceptance of such assessments will facilitate the UME transition toward competency-based medical education. PMID- 28991845 TI - A Purpose-Driven Fourth Year of Medical School. AB - The fourth year of medical school has been repeatedly found to be ineffective, and concerns exist about its purpose and academic quality, as well as grade inflation. Since Flexner, the purpose of undergraduate medical training has moved from readiness for independent practice to readiness for postgraduate training. However, training directors report that medical graduates are inadequately prepared to enter residency. The authors propose a fourth year with two components: first, a yearlong, longitudinal ambulatory experience of at least three days each week on an interprofessional team with consistent faculty supervision and mentoring, increasing independence, and a focus on education; and second, rigorous clinical-scales-based assessment of meaningful outcomes.In the proposed model, the medical student has generous time with a limited panel of patients, and increasing autonomy, with faculty moving from supervising physicians to collaborating physicians. There is regular assessment and formative feedback. This more independent, longitudinal clinical experience uniquely allows assessment of the most meaningful work-based performance outcomes-that is, patient outcomes assessed by validated clinical scales. The proposed fourth year will require a realignment of resources and faculty time; however, models already exist. Barriers and possible solutions are discussed.A purpose-driven, assessment rich fourth year with patient and supervisor continuity will provide real-world experience, making medical graduates more competent and confident on the first day of residency. Use of clinical scales will also allow educators new confidence that the performance-based competence of these more experienced and expert graduates leads to demonstrable collaboration, healing, and good patient outcomes. PMID- 28991847 TI - Medical Humanities: The Rx for Uncertainty? AB - While medical students often fear the avalanche of knowledge they are required to learn during training, it is learning to translate that knowledge into wisdom that is the greatest challenge of becoming a doctor. Part of that challenge is learning to tolerate ambiguity and uncertainty, a difficult feat for doctors who are taught to question anything that is not evidence based or peer reviewed. The medical humanities specialize in this ambiguity and uncertainty, which are hallmarks of actual clinical practice but rarely addressed in medical education. The humanities also force reflection and contemplation-skills that are crucial to thoughtful decision making and to personal wellness. Beyond that, the humanities add a dose of joy and beauty to a training process that is notoriously frugal in these departments. Well integrated, the humanities can be the key to transforming medical knowledge into clinical wisdom. PMID- 28991846 TI - A Multi-Institutional Longitudinal Faculty Development Program in Humanism Supports the Professional Development of Faculty Teachers. AB - The authors describe the first 11 academic years (2005-2006 through 2016-2017) of a longitudinal, small-group faculty development program for strengthening humanistic teaching and role modeling at 30 U.S. and Canadian medical schools that continues today. During the yearlong program, small groups of participating faculty met twice monthly with a local facilitator for exercises in humanistic teaching, role modeling, and related topics that combined narrative reflection with skills training using experiential learning techniques. The program focused on the professional development of its participants. Thirty schools participated; 993 faculty, including some residents, completed the program.In evaluations, participating faculty at 13 of the schools scored significantly more positively as rated by learners on all dimensions of medical humanism than did matched controls. Qualitative analyses from several cohorts suggest many participants had progressed to more advanced stages of professional identity formation after completing the program. Strong engagement and attendance by faculty participants as well as the multimodal evaluation suggest that the program may serve as a model for others. Recently, most schools adopting the program have offered the curriculum annually to two or more groups of faculty participants to create sufficient numbers of trained faculty to positively influence humanistic teaching at the institution.The authors discuss the program's learning theory, outline its curriculum, reflect on the program's accomplishments and plans for the future, and state how faculty trained in such programs could lead institutional initiatives and foster positive change in humanistic professional development at all levels of medical education. PMID- 28991848 TI - The Feedback Tango: An Integrative Review and Analysis of the Content of the Teacher-Learner Feedback Exchange. AB - PURPOSE: To conduct an integrative review and analysis of the literature on the content of feedback to learners in medical education. METHOD: Following completion of a scoping review in 2016, the authors analyzed a subset of articles published through 2015 describing the analysis of feedback exchange content in various contexts: audiotapes, clinical examination, feedback cards, multisource feedback, videotapes, and written feedback. Two reviewers extracted data from these articles and identified common themes. RESULTS: Of the 51 included articles, about half (49%) were published since 2011. Most involved medical students (43%) or residents (43%). A leniency bias was noted in many (37%), as there was frequently reluctance to provide constructive feedback. More than one quarter (29%) indicated the feedback was low in quality (e.g., too general, limited amount, no action plans). Some (16%) indicated faculty dominated conversations, did not use feedback forms appropriately, or provided inadequate feedback, even after training. Multiple feedback tools were used, with some articles (14%) describing varying degrees of use, completion, or legibility. Some articles (14%) noted the impact of the gender of the feedback provider or learner. CONCLUSIONS: The findings reveal that the exchange of feedback is troubled by low-quality feedback, leniency bias, faculty deficient in feedback competencies, challenges with multiple feedback tools, and gender impacts. Using the tango dance form as a metaphor for this dynamic partnership, the authors recommend ways to improve feedback for teachers and learners willing to partner with each other and engage in the complexities of the feedback exchange. PMID- 28991849 TI - U.S. Physician-Scientist Workforce in the 21st Century: Recommendations to Attract and Sustain the Pipeline. AB - The U.S. physician-scientist (PS) workforce is invaluable to the nation's biomedical research effort. It is through biomedical research that certain diseases have been eliminated, cures for others have been discovered, and medical procedures and therapies that save lives have been developed. Yet, the U.S. PS workforce has both declined and aged over the last several years. The resulting decreased inflow and outflow to the PS pipeline renders the system vulnerable to collapsing suddenly as the senior workforce retires. In November 2015, the Alliance for Academic Internal Medicine hosted a consensus conference on the PS workforce to address issues impacting academic medical schools, with input from early-career PSs based on their individual experiences and concerns. One of the goals of the conference was to identify current impediments in attracting and supporting PSs and to develop a new set of recommendations for sustaining the PS workforce in 2016 and beyond. This Perspective reports on the opportunities and factors identified at the conference and presents five recommendations designed to increase entry into the PS pipeline and nine recommendations designed to decrease attrition from the PS workflow. PMID- 28991850 TI - Aligning Education With Health Care Transformation: Identifying a Shared Mental Model of "New" Faculty Competencies for Academic Faculty. AB - PURPOSE: To develop a potential competency framework for faculty development programs aligned with the needs of faculty in academic health centers (AHCs). METHOD: In 2014 and 2015, the authors interviewed 23 health system leaders and analyzed transcripts using constant comparative analysis and thematic analysis. They coded competencies and curricular concepts into subcategories. Lead investigators reviewed drafts of the categorization themes and subthemes related to gaps in faculty knowledge and skills, collapsed and combined competency domains, and resolved disagreements via discussion. RESULTS: Through analysis, the authors identified four themes. The first was core functional competencies and curricular domains for conceptual learning, including patient-centered care, health care processes, clinical informatics, population and public health, policy and payment, value-based care, and health system improvement. The second was the need for foundational competency domains, including systems thinking, change agency/management, teaming, and leadership. The third theme was paradigm shifts in how academic faculty should approach health care, categorized into four areas: delivery, transformation, provider characteristics and skills, and education. The fourth theme was the need for faculty to be aware of challenges in the culture of AHCs as an influential context for change. CONCLUSIONS: This broad competency framework for faculty development programs expands existing curricula by including a comprehensive scope of health systems science content and skills. AHC leaders can use these results to better align faculty education with the real time needs of their health systems. Future work should focus on optimal prioritization and methods for teaching. PMID- 28991851 TI - Quantitative Analysis of Endothelial Cell Loss in Preloaded Descemet Membrane Endothelial Keratoplasty Grafts. AB - PURPOSE: Availability of preloaded Descemet membrane endothelial keratoplasty (pDMEK) tissue may increase acceptance of DMEK in surgical management of endothelial disease. The goal of this study was to determine the safety of pDMEK grafts for 24 hours before surgery by analyzing endothelial cell loss (ECL) using 2 image analysis software programs. METHODS: A total of 18 cadaveric corneas were prepared for DMEK using a standardized technique and loaded in a modified Jones tube injector. Nine of the corneas were injected into Calcein AM vital dye after 1 minute (controls), and the remaining 9 corneas were left preloaded for 24 hours before injection into vital dye for staining. The stained corneas were imaged using an inverted confocal microscope. ECL was then analyzed and quantified by 2 different graders using 2 image analysis software programs. RESULTS: The control DMEK tissue resulted in 22.0% +/- 4.0% ECL compared with pDMEK tissue, which resulted in 19.2% +/- 7.2% ECL (P = 0.31). Interobserver agreement was 0.93 for MetaMorph and 0.92 for Fiji. The average time required to process images with MetaMorph was 2 +/- 1 minutes and with Fiji was 20 +/- 10 minutes. Intraobserver agreement was 0.97 for MetaMorph and 0.93 for Fiji. CONCLUSIONS: Preloading DMEK tissue is safe and may provide an alternative technique for tissue distribution and surgery for DMEK. The use of MetaMorph software for quantifying ECL is a novel and accurate imaging method with increased efficiency and reproducibility compared with the previously validated Fiji. PMID- 28991852 TI - Preparation and Biomechanical Properties of an Acellular Porcine Corneal Stroma. AB - PURPOSE: To construct an acellular porcine corneal stroma (aPCS) as a human corneal stroma alternative and to further explore its biomechanical properties. METHODS: A combination of DNA-RNA enzymes and ultrasound technology was used to strip the native porcine corneal cells. The microstructure of aPCS was observed by H&E staining, DAPI staining, and alpha-Gal tests. The mechanical properties were detected by a tension machine. Cytotoxicity of aPCS was measured by the MTT assay. The subcutaneous embedding experiment in rats was also used to detect immunity and degradation. The aPCS was transplanted into the rabbit cornea by lamellar keratoplasty, general observations were made at 3 days, 1 week, 1 month, and 3 months after implantation, respectively. RESULTS: The microstructure and mechanical properties of aPCS were not damaged during the decellularization process. The aPCS extracts had no significant cytotoxicity on human corneal stroma cells. Moreover, the subcutaneous embedding experiment in rats demonstrated that aPCS could not be degraded and induced no immune reaction in and around the transplanted discs. More important is that the aPCS reconstructed normal corneal stroma and maintained corneal transparency and thickness, with almost no neovascularization and inflammation at 3 months after surgery. CONCLUSIONS: The aPCS prepared in this study had good biocompatibility, safety, and low antigenicity, which has great potential for corneal disease treatment. PMID- 28991853 TI - Simulated Keratometry Versus Total Corneal Power by Ray Tracing: A Comparison in Prediction Accuracy of Intraocular Lens Power. AB - PURPOSE: To investigate the relationship between corneal powers measured by simulated keratometry (Sim-K) and ray tracing and understand whether their difference influences intraocular lens (IOL) power calculation. METHODS: In a first sample of healthy eyes, corneal curvature was measured using a rotating Scheimpflug camera (Sirius, CSO). Sim-K was obtained from anterior corneal curvature using the 1.3375 keratometric index. Ray tracing was performed through both corneal surfaces to calculate the total corneal power (TCP). The difference between Sim-K and TCP was correlated with various parameters. In a second sample of patients undergoing cataract surgery, IOL power was subsequently calculated using both Sim-K and TCP. RESULTS: In the first sample (114 eyes), Sim-K (43.64 +/- 1.44 D) was higher than TCP (43.07 +/- 1.41 D, P < 0.0001); the difference ranged between 0.07 and 1.95 D and correlated with the anterior/posterior (A/P) ratio (r = 0.7292, P < 0.0001), which ranged between 1.10 and 1.30. In the second sample (107 eyes), the A/P ratio influenced the outcomes of the Holladay 1 and SRK/T, but not Haigis and Hoffer Q formulas. However, using TCP, which takes the A/P ratio into account, did not improve the prediction error of any formula. CONCLUSIONS: Sim-K provides a higher corneal power compared with TCP. This difference is not constant but depends on the A/P ratio and can influence the refractive outcome of IOL power calculation by theoretical formulas. However, TCP values do not improve the results of these formulas, as they were developed for keratometric values such as Sim-K. PMID- 28991854 TI - Alkali Burn Induced Corneal Spontaneous Pain and Activated Neuropathic Pain Matrix in the Central Nervous System in Mice. AB - PURPOSE: To explore whether alkali burn causes corneal neuropathic pain and activates the neuropathic pain matrix in the central nervous system in mice. METHODS: A corneal alkali burn mouse model (grade II) was used. The mechanical threshold in the cauterized area was tested using Von Frey hairs. Spontaneous pain behavior was investigated with conditioned place preference. Phosphor extracellular signal-regulated kinase (ERK), which is a marker for neuronal activation in chronic pain processing, was investigated in several representative areas of the neuropathic pain matrix: the 2 regions of the spinal trigeminal nucleus (subnucleus interpolaris/caudalis, Vi/Vc; subnucleus caudalis/upper cervical cord, Vc/C1), insular cortex, anterior cingulated cortex (ACC), and the rostroventral medulla (RVM). Furthermore, pharmacologically blocking pERK activation in the ACC of alkali burn mice was performed in a separate study. RESULTS: Corneal alkali burn caused long-lasting damage to the corneal subbasal nerve fibers, and mice exhibited spontaneous pain behavior. By testing in several representative areas of the neuropathic pain matrix in the higher nervous system, phosphor ERK was significantly activated in Vc/C1, but not in Vi/Vc. Also, ERK was activated in the insular cortex, ACC, and RVM. Furthermore, pharmacologically blocking ERK activation in the ACC abolished alkali burn induced corneal spontaneous pain. CONCLUSIONS: Alkali burn could cause corneal spontaneous pain and activate the neuropathic pain matrix in the central nervous system. Furthermore, activation of ERK in the ACC is required for alkali burn induced corneal spontaneous pain. PMID- 28991857 TI - Impact of Histological and Endoscopic Remissions on Clinical Recurrence and Recurrence-free Time in Ulcerative Colitis. AB - BACKGROUND: Clinical and endoscopic remissions constitute the therapeutic goals in ulcerative colitis (UC). Histological healing is currently not a target in UC. This study aims to determine the impact of the definition of endoscopic remission (Mayo endoscopic subscore [MSe] 0-1) and histological activity in the recurrence of UC and recurrence-free survival time. METHODS: Patients with UC in clinical remission (partial Mayo score <= 1) and endoscopic remission (MSe <= 1) who underwent colonoscopy with biopsies between March 2010 and December 2013 were included. The validated Nancy score was used to evaluate histological activity, which considers inactivity if 0 to 1 and activity if 2 to 4. The recurrence-free time was evaluated and recurrence was defined as partial Mayo score >= 2, therapy to induce remission, hospitalization, or colectomy. Predictive factors associated with recurrence and time to recurrence were determined. RESULTS: Sixty patients were included; 58.3% (n = 35) were women, with a mean age of 52.7 years. MSe = 1 was observed in 46.7% (n = 28) and histological activity in 38.3% (n = 23). Clinical recurrence occurred in 31.7% (n = 19) of patients, with a cumulative risk of 17.1%/24.5%/26.7%/40.1% at 12/24/36/48 months, respectively. MSe = 1 (P = 0.02) and histological activity (P = 0.007) were significantly associated with recurrence. Of these, only histological activity (P = 0.03) was an independent predictive factor of recurrence. Patients with MSe = 1 (P = 0.02) and with histological activity (P = 0.01) had a significantly shorter recurrence-free time in univariate analysis. In multivariate analysis, only histological activity (P = 0.02) was an independent predictive factor of lower recurrence-free time. CONCLUSION: The presence of histological activity represents an independent predictive factor of recurrence and time to recurrence, which was not verified with MSe 0 to 1. PMID- 28991855 TI - Cancer Risk in 2621 Chinese Patients with Inflammatory Bowel Disease: A Population-based Cohort Study. AB - BACKGROUND: Studies on cancer risk in inflammatory bowel disease (IBD) have yielded inconsistent results. We conducted a population-based study to determine the risk of cancer in patients with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: Using a territory-wide IBD registry in Hong Kong, we identified 2621 patients with IBD and no history of cancer from 1990 to 2016. We followed them from diagnosis until either September 2016, cancer development, proctocolectomy, or death. Standardized incidence ratios (SIRs) of overall cancer and site-specific cancers were calculated. RESULTS: Of 2621 patients with IBD (1108 CD; 1603 UC; median age, 49 yr; 59.5% men) followed for 26,234 person years, 88 patients developed cancer after IBD diagnosis. Patients with CD had an increased risk of anorectal cancers (SIR 4.11; 95% confidence interval (CI), 1.84 9.14) and hematological cancers (SIR 3.86, 95% CI, 1.61-9.27) including leukemia (SIR 5.98; 95% CI, 1.93-18.54). Nonmelanoma skin cancer was significantly increased in both CD and UC (CD: SIR 13.88; 95% CI, 1.95-98.51; UC: SIR 9.05; 95% CI, 2.26-36.19). Patients with CD had a higher risk of renal-cell carcinoma (SIR 6.89; 95% CI, 2.22-21.37), and patients with UC had a higher risk of prostate cancer (SIR 2.47; 95% CI, 1.24-4.95). CONCLUSIONS: In a population-based study, Chinese patients with CD are at an increased risk of anorectal cancers and hematological cancers compared with the general population. A higher risk of nonmelanoma skin cancer was also observed in CD and UC. Cancer surveillance should be considered. PMID- 28991858 TI - Large Registry Epidemiology in IBD. AB - There are different types of large registries which can be harnessed for inflammatory bowel disease research. Not one registry can answer all types of research questions. It is important for both the researchers using the registries and readers of the reports generated, to be aware of the different strengths and weaknesses of each registry and whether the questions posed can reliably be answered. In this review, the use of large administrative databases/registries are discussed in the context of studying descriptive epidemiology, outcomes of inflammatory bowel disease, pharmacoepidemiology, and etiologic research. PMID- 28991856 TI - Genetic Polymorphisms in Fatty Acid Metabolism Modify the Association Between Dietary n3: n6 Intake and Risk of Ulcerative Colitis: A Prospective Cohort Study. AB - INTRODUCTION: High intake of dietary n-3 polyunsaturated fatty acids (PUFA) is associated with a decreased risk of ulcerative colitis (UC) and Crohn's disease (CD). However, results have been heterogeneous suggesting that genetic variations in PUFA metabolism may modify this risk. METHODS: We conducted a case-control study nested within 2 prospective cohorts, the Nurses' Health Study (NHS) and NHS II. Among women providing blood (n = 62,437) or buccal cells (n = 59,543) for genotyping, we confirmed new diagnoses of CD or UC. Dietary intake was assessed 4 years before diagnosis. Confirmed cases were matched 1:2 to controls. Subjects were genotyped for single nucleotide polymorphisms at CYP4F3, FADS1, and FADS2 loci. Conditional logistic regression models examined the interaction between genotype, n3:n6 PUFA intake and risk of CD and UC. RESULTS: Our study included 101 CD and 139 UC patients matched to 495 controls. On multivariable analysis, high intake of n3:n6 PUFA (above median) demonstrated a trend toward reduced risk of UC (Odds ratio [OR] 0.71, 95% confidence interval [CI], 0.47-1.09, P = 0.11). High n3:n6 PUFA intake was associated with a reduced risk of UC in individuals with the GG/AG genotype at a single nucleotide polymorphism in CYP4F3 (OR 0.57, 95% CI, 0.32-0.99) but not those with the AA genotype (OR 0.95, 95% CI, 0.47 1.93) (P-interaction = 0.049). No gene-diet interactions were noted for CD. CONCLUSIONS: The association between dietary n3:n6 PUFA intake and risk of UC may be modified variants at CYP4F3. Further gene-environment studies of the association between diet and IBD risk are warranted. PMID- 28991859 TI - PUFAs and IBD: Is There a Relationship? PMID- 28991860 TI - How to Avoid Primary Nonresponders to Infliximab in Crohn's Disease. PMID- 28991861 TI - Diagnostic and Therapeutic Challenges. PMID- 28991862 TI - Isolated Retinal Metastasis From Breast Cancer. PMID- 28991863 TI - Diagnostic and Therapeutic Challenges. PMID- 28991864 TI - Bilateral Large Colloid Drusen in a Young Adult. PMID- 28991865 TI - Intraoperative Injection of Intravitreal Dexamethasone Implant Using a Vitrectomy Trocar-Assisted Technique. PMID- 28991866 TI - RETINAL LASER AND PHOTOGRAPHY PRACTICE EYE MODEL: A Cost-Effective Innovation to Improve Training Through Simulation. PMID- 28991868 TI - Type 2 Diabetes in the Older Adult: The Need for Assessment of Frailty. PMID- 28991869 TI - Mesenteric Artery Growth Improves Circulation (MAGIC) in Midaortic Syndrome. PMID- 28991870 TI - Saline Solution (1.25%) for Septic Patients With Active Stroke. PMID- 28991871 TI - Treatment of ST Elevation Myocardial Infarction in the Setting of Infective Endocarditis: A Need for Treatment Guidelines. PMID- 28991872 TI - Comparison of an Updated Risk Stratification Index to Hierarchical Condition Categories. AB - BACKGROUND: The Risk Stratification Index and the Hierarchical Condition Categories model baseline risk using comorbidities and procedures. The Hierarchical Condition categories are rederived yearly, whereas the Risk Stratification Index has not been rederived since 2010. The two models have yet to be directly compared. The authors thus rederived the Risk Stratification Index using recent data and compared their results to contemporaneous Hierarchical Condition Categories. METHODS: The authors reimplemented procedures used to derive the original Risk Stratification Index derivation using the 2007 to 2011 Medicare Analysis and Provider review file. The Hierarchical Condition Categories were constructed on the entire data set using software provided by the Center for Medicare and Medicaid Services. C-Statistics were used to compare discrimination between the models. After calibration, accuracy for each model was evaluated by plotting observed against predicted event rates. RESULTS: Discrimination of the Risk Stratification Index improved after rederivation. The Risk Stratification Index discriminated considerably better than the Hierarchical Condition Categories for in-hospital, 30-day, and 1-yr mortality and for hospital length-of stay. Calibration plots for both models demonstrated linear predictive accuracy, but the Risk Stratification Index predictions had less variance. CONCLUSIONS: Risk Stratification discrimination and minimum-variance predictions make it superior to Hierarchical Condition Categories. The Risk Stratification Index provides a solid basis for care-quality metrics and for provider comparisons. PMID- 28991874 TI - TO THE EDITOR. PMID- 28991876 TI - Sensitizing Surgeons to Their Outcome Has No Measurable Short-term Benefit. AB - OBJECTIVE: Investigate if involving surgeons in outcome prediction-research and having them use a dedicated Electronic-Health-Record that provides feedback, improves patients' outcome. BACKGROUND: Improvement of clinical outcome mainly relies on the declaration of adverse events, identification of their predictors, self-assessment, and feedback. METHODS: Thirteen French Hepato-Pancreato-Biliary centers made commitment to include all patients undergoing elective hepatectomies in an observational study. Each center was given access to a dedicated website, where perioperative data were prospectively collected. The website provided real time individual and comparative feedback of outcome and was also intended to perform prognostication studies. The hypothesis was that by using this strategy, the length-of-stay would be reduced by 10%. Power-calculation implied the inclusion of 1720 patients. Secondary endpoints were 90-day mortality, severe morbidity, and the comprehensive-complication index. RESULTS: Only 5 of the 13 participating centers were fully compliant in enrolling their patients and the inclusion period was extended by 1-year (October 2012-October 2015) to meet the objective. During this period, the collaborative group published 9 studies based on the study data (median impact factor = 8.327) that identified quantitative clinical variables, qualitative clinical variables, and nonclinical variables influencing outcome. For patients enrolled by the 5 active centers (n = 1752), there was no improvement in length of stay (13.3 vs 12.4 days, P = 0.287), severe complications (23.6 vs 20.5%, P = 0.134), the complication comprehensive index (24.0 vs 24.9, P = 0.448), mortality (4.1 vs 3.9%, P = 0.903), or unplanned readmissions (7.2 vs 8.4%, P = 0.665), even after adjusting for confounders. CONCLUSION: Simply sensitizing surgeons to their outcome has no measurable short term clinical benefit. PMID- 28991879 TI - Risks Versus Benefits of Anticoagulation for Atrial Fibrillation in Cirrhotic Patients. AB - BACKGROUND & AIMS: To evaluate the clinical benefits and risks of anticoagulation with warfarin in cirrhotic patients with atrial fibrillation (AF). METHODS: A total of 465 cirrhotic patients diagnosed with nonvalvular AF were retrospectively analyzed. We compared incidences of ischemic stroke and major bleeding events between the 2 groups and examined the factors predicting ischemic stroke or major bleeding events. RESULTS: Of 465 patients with AF, 113 (24.3%) received warfarin. Warfarin users had a lower mean Child-Pugh score (6.1 +/- 1.5 vs. 7.6 +/- 2.6) and a higher mean CHA2DS2VASc score (2.0 +/- 2.5 vs. 1.7 +/- 1.3) than nonusers (P's < 0.05). Overall, the incidence of ischemic stroke was low in cirrhotic patients with AF. It was not dependent on the CHA2DS2VASc score (hazard ratio, 1.40; 95% confidence interval, 0.96-2.05; P = 0.081), and was comparable in warfarin users (0.9%/person-year) and nonusers (1.2%/person-year). However, the incidence of major bleeding events was significantly higher in warfarin users (5.9% vs. 2.6%; P < 0.05). A multivariate analysis identified warfarin use (2.60; 95% confidence interval, 1.32-5.12) and Child-Pugh score (1.25; 1.04-1.49) as independently associated with bleeding events in these cirrhotic patients (P's < 0.05). There was no correlation between HAS-BLED score and risk of major bleeding (1.20; 0.95-1.52; P = 0.123). CONCLUSIONS: Anticoagulation with warfarin in cirrhotic patients with AF may not significantly reduce the risk of ischemic stroke, whereas it increases hemorrhagic complications. PMID- 28991878 TI - Fatty Acid-Mediated Stromal Reprogramming of Pancreatic Stellate Cells Induces Inflammation and Fibrosis That Fuels Pancreatic Cancer. AB - OBJECTIVES: Pancreatic ductal adenocarcinoma is one of the deadliest diseases worldwide. Fatty acids (FAs) have properties that affect both cancer cells and tumor environment. We assessed the effects of FAs on malignant characteristics in a pancreatic cancer and pancreatic stellate cell (PSC) coculture model. This study aimed to clarify the FA signature of PSC-derived inflammation and fibrosis in vitro and in a clinicopathological analysis. METHODS: The in vitro model involved coculture of the human pancreatic cancer cell lines PANC-1 and MIA PaCa 2 with human PSCs. Clinical histological samples were analyzed to characterize the surgical margins of samples from patients who received distal pancreatectomies. RESULTS: The pancreatic cancer cells took up lipids from the culture media. Saturated and unsaturated FAs were required to induce inflammatory responses in human PSCs, and the cocultures showed fibrotic changes. Clinical samples from pancreatic ductal adenocarcinoma patients had more fatty and fibrotic changes in the normal tissue in the surgical margins than samples from noncancer patients. CONCLUSIONS: Inflammation and fibrosis levels were increased in pancreatic cancer specimens, supporting the in vitro observations and suggesting that PSCs contribute to pancreatic carcinogenesis. Pancreatic stellate cells thus represent a potential therapeutic target for suppressing stromal changes in pancreatic cancer. PMID- 28991877 TI - Cell Cycle Protein Expression in Neuroendocrine Tumors: Association of CDK4/CDK6, CCND1, and Phosphorylated Retinoblastoma Protein With Proliferative Index. AB - OBJECTIVES: Dysregulation of the cell cycle has been observed and implicated as an etiologic factor in a range of human malignancies, but remains relatively unstudied in neuroendocrine tumors (NETs). We evaluated expression of key proteins involved in cell cycle regulation in a large cohort of NETs. METHODS: We evaluated immunohistochemical expression of CDKN1B, CDKN1A, CDKN2A, CDK2, CDK4, CDK6, cyclin D1, cyclin E1, and phosphorylated retinoblastoma protein (phospho RB1) in a cohort of 267 patients with NETs. We then explored associations between cell cycle protein expression, mutational status, histologic features, and overall survival. RESULTS: We found that high expression of CDK4, CDK6, CCND1, and phospho-RB1 was associated with higher proliferative index, as defined by MKI67. We additionally observed a trend toward shorter overall survival associated with low expression of CDKN1B. This association seemed strongest in SINETs (multivariate hazards ratio, 2.04; 95% confidence interval, 1.06-3.93; P = 0.03). We found no clear association between CDKN1B mutation and protein expression. CONCLUSIONS: Our results suggest that dysregulation and activation of the CDK4/CDK6-CCND1-phospho-RB1 axis is associated with higher proliferative index in NETs. Investigation of the therapeutic potential of CDK4/CDK6 inhibitors in higher grade NETs is warranted. PMID- 28991880 TI - Folic Acid Impairs the Uptake of 5-Methyltetrahydrofolate in Human Umbilical Vascular Endothelial Cells. AB - BACKGROUND: Adequate folate status supports endothelial structure and function. Folic acid (FA), an oxidized synthetic folate, which is present in the plasma of patients consuming fortified food or FA supplements, may impair cellular uptake of physiological, reduced folates. We studied the effect of FA on uptake of the dominant circulatory folate, 5-methyltetrahydrofolate (5MTHF) in endothelial cells. METHODS AND RESULTS: For short-term effects of FA, primary human umbilical vein endothelial cells (HUVECs) were maintained in growth medium containing 200 nM 5MTHF and preincubated with 20 nM FA 10 minutes before the 5MTHF uptake assessment. For long-term effects, HUVECs were cultured for 3 passages in growth medium containing either 200 nM 5MTHF, or a combination of 100 nM 5MTHF and 100 nM FA. 5MTHF uptake was assessed after exposing cells to 200 nM [C5]-5MTHF, after which intracellular [C5]-5MTHF was quantified using liquid chromatography/tandem mass spectrometry. Acute FA exposure caused a 57% reduction in 5MTHF uptake compared with control conditions (51 +/- 12 vs. 22 +/- 7 fmol.min.mg protein; P = 0.01). Long-term exposure to FA reduced 5MTHF uptake by 41% (51 +/- 12 vs. 30 +/- 11 fmol.min.mg protein; P = 0.05) and reduced total cellular 5MTHF levels by 47 +/- 21% in HUVEC (P = 0.02). CONCLUSION: Unmetabolized FA, which appears in the plasma after consumption of fortified food or FA supplements, may impair uptake of 5MTHF, the dominant bioactive form of folate, in HUVEC. PMID- 28991881 TI - Scaling up Pediatric HIV Testing by Incorporating Provider-Initiated HIV Testing Into all Child Health Services in Hurungwe District, Zimbabwe. AB - BACKGROUND: Practical ways are needed to scale-up pediatric HIV testing in sub Saharan Africa, where testing is usually limited to HIV-exposed children in maternal and child health clinics. METHODS: We implemented an enhanced pediatric HIV testing program in 33 health facilities in Zimbabwe by integrating HIV testing into all pediatric health services. We collected individual data on children tested by having health care workers complete a program-specific child health booklet. We compared numbers of children tested before and during the program using routinely collected aggregate program data reported by health facilities. RESULTS: A total of 12,556 children aged 0-5 years were recorded in child health booklets; 9431 (75.1%) had information on HIV testing, of whom 7326 (77.7%) were tested; 7167 had test results of whom 122 (1.7%) were HIV-infected. Among children seen in outpatient clinics, 82.1% were tested compared with 66.5% tested among children seen in maternal/child health clinics. Of the 122 HIV infected children identified, 77 (63.1%) could be missed under existing pediatric testing guidelines. The number of HIV-infected children identified during the 6 month program increased by 55% compared with the prior 6-month period (RR = 1.55, 95% CI: 1.22 to 1.96). Factors independently associated with HIV infection included being malnourished (adjusted odds ratio [AOR] = 7.7, 95% CI: 2.1 to 28.6), being exposed to TB (AOR = 8.1, 95% CI: 2.0 to 32.2), and having an HIV infected mother (AOR = 41.6, 95% CI: 15.9 to 108.8). CONCLUSIONS: Integrating HIV testing into all pediatric health services is feasible and can assist in identifying HIV-infected children who could be missed in current testing guidelines. PMID- 28991882 TI - Belief in Treatment as Prevention and Its Relationship to HIV Status and Behavioral Risk. AB - BACKGROUND: We evaluated attitudes toward treatment as prevention (TasP) among gay, bisexual, and other men who have sex with men (GBM) in Vancouver, Canada. METHODS: Sexually active GBM, aged >=16 years, were recruited between 2012 and 2015 using respondent-driven sampling. At each 6-month follow-up, participants completed a computer-administered questionnaire and nursing visit. Repeated measures latent class analysis, grouped by self-reported serostatus, identified patterns of TasP endorsement by considering TasP-related awareness, attitudes, and behavior. Binary logistic regression identified covariates of class membership. Bivariate interactions with visit number identified factors associated with longitudinal changes in class membership. RESULTS: A total of 774 men provided 2590 observations. Of these, 698 enrolled in the cohort, 575 had at least 1 follow-up visit. Among these, the median follow-up time was 1.98 years (Q1-Q2: 1.49-2.49 years). Repeated-measures latent class analysis identified 3 classes: "unaware" (64.2% HIV negative/unknown vs. 29.2% of HIV positive), "skeptical" (29.7% vs. 23.1%), and "believing" (6.1% vs. 47.7%). Membership in classes representing higher TasP endorsement was associated with greater odds of condomless anal sex and having more sexual partners. Age, sexual orientation, ethnicity, substance use, and social time spent with other GBM were also associated with class membership. Longitudinally, class membership was stable among HIV-positive men but shifted toward greater TasP endorsement among HIV negative/unknown men. For HIV-negative/unknown men, increasing endorsement was positively associated with greater education, being employed, being in a relationship, and substance use and inversely associated with recent serodiscordant condomless anal sex or sexually transmitted infection diagnosis. CONCLUSIONS: Over time, disparities in TasP diffusion by HIV status have lessened, although continue to persist across other key social strata. PMID- 28991883 TI - Inflammation-Related Morbidity and Mortality Among HIV-Positive Adults: How Extensive Is It? AB - OBJECTIVE: To determine the rate of grade 4, potentially life-threatening events not attributable to AIDS, cardiovascular disease (CVD), or non-AIDS cancer among participants on antiretroviral therapy and to describe associations of these events with interleukin-6 (IL-6) and D-dimer. DESIGN: Cohort study. METHODS: HIV infected participants on antiretroviral therapy (N = 3568) with an HIV-RNA level <= 500 copies/mL were followed for grade 4, AIDS, CVD, non-AIDS cancer, and all cause mortality events. Grade 4 events were further classified masked to biomarker levels as reflecting chronic inflammation-related disease (ChrIRD) or not (non-ChrIRD). Associations of baseline IL-6 and D-dimer with events were studied using Cox models. RESULTS: Over a median follow-up of 4.3 years, 339 participants developed a grade 4 event (22.9 per 1000 person-years); 165 participants developed a ChrIRD grade 4 event (10.7 per 1000 person-years). Grade 4 events were more common than AIDS (54 participants), CVD (132), and non-AIDS cancer (80) events, any of which developed in 252 participants (17.1 per 1000 person-years). Grade 4 and AIDS events were associated with similar risks of death. Higher IL-6 [hazard ratio (HR) = 1.19 per doubling of biomarker; P = 0.003] and D-dimer (HR = 1.23; P < 0.001) levels were associated with an increased risk of grade 4 events. IL-6 associations were stronger for ChrIRD (HR = 1.38; P < 0.001) than non-ChrIRD grade 4 events (HR = 1.11; P = 0.21). CONCLUSIONS: Morbidity and mortality associated with activation of inflammatory and coagulation pathways include conditions other than AIDS, CVD, and non-AIDS cancer events. Effective inflammation-dampening interventions could greatly affect the health of people with HIV. PMID- 28991884 TI - HIV Continuum of Care for Youth in the United States. AB - BACKGROUND: Beneficial HIV treatment outcomes require success at multiple steps along the HIV Continuum of Care. Youth living with HIV are a key population, and sites in the Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) are known for modeling optimum HIV adolescent care. METHODS: A longitudinal cohort study conducted at 14 network sites across the United States assessed how the later steps of the Continuum of Care were achieved among the youth: engagement, treatment, and viral load (VL) suppression. Youth aged 13-24 who were behaviorally infected with HIV and linked to care at an ATN-affiliated site were eligible to participate. RESULTS: A total of 467 youth were enrolled and had 1 year of available data. Most were aged 22-24 (57%), male (79%), and black/non Hispanic (71%). Most used alcohol (81%) and marijuana (61%) in the 3 months before enrollment, and 40% had a history of incarceration. Among this cohort of youth, 86% met criteria for care engagement; among these, 98% were prescribed antiretroviral therapy and 89% achieved VL suppression. Sustained VL suppression at all measured time points was found among 59% with initial suppression. Site characteristics were notable for the prevalence of adherence counseling (100%), case management (100%), clinic-based mental health (93%), and substance use (64%) treatment. CONCLUSIONS: Youth living with HIV in the United States can be successfully treated at health care sites with experience, excellence, and important resources and services. Sustained VL suppression may be an important step to add to the Continuum of Care for youth. PMID- 28991885 TI - Predictors of HIV, HIV Risk Perception, and HIV Worry Among Adolescent Girls and Young Women in Lilongwe, Malawi. AB - BACKGROUND: Adolescent girls and young women (AGYW) in sub-Saharan Africa have high HIV prevalence and incidence. We sought to understand which HIV risk factors individually and in combination contribute to risk, and whether these factors are associated with HIV worry and risk perception. SETTING: This study is ongoing at 4 public health centers in Lilongwe, Malawi (2016-2017). METHODS: AGYW of 15-24 years old were recruited to participate in a study assessing 4 models of service delivery. At each health center, participants completed a baseline survey assessing socioeconomic, behavioral, biomedical, and partnership characteristics; self-reported HIV status; and, if HIV-uninfected, HIV risk perception (high versus low or none) and HIV worry (any versus none). We analyzed associations between baseline characteristics and HIV prevalence, risk perception, and worry. RESULTS: Among 1000 AGYW, median age was 19 years (IQR: 17-21). Thirty-three participants reported being HIV-infected. Fifteen characteristics were associated with HIV infection. Having more risk factors was associated with higher HIV prevalence (<=4 factors, 0.5%; 5-8 factors, 6%; >8 factors, 21%). Having more risk factors was also associated with higher risk perception (P < 0.001) and higher worry (P < 0.001). However, among those with >=8 risk factors, 52% did not consider themselves to be at high risk and 21% did not report any HIV worry. CONCLUSIONS: Most AGYW perceive little risk of HIV acquisition, even those at highest risk. As a critical gap in the HIV prevention cascade, accurate risk perception is needed to tailor effective and sustained combination prevention strategies for this vulnerable population. PMID- 28991886 TI - Brief Report: Estimated Incidence of Perinatally Acquired HIV Infection in the United States, 1978-2013. AB - BACKGROUND: An incidence of perinatally acquired HIV infection less than 1:100,000 live births is one of the Centers for Disease Control and Prevention (CDC) goals of the United States. Such an estimate has only been possible in recent years because regular nationwide data were lacking. METHOD: Using previously published CDC estimates of the number of infants born with HIV infection in the United States (interpolating for years for which there was no published estimate), and census data on the annual number of live-born infants, estimated incidence was calculated for 1978-2013. Exact 95% confidence intervals (CIs) were calculated using the Poisson distribution. RESULTS: Estimated incidence of perinatally acquired HIV infection peaked at 43.1 (95% CI: 41.1 to 45.1) in 1992 and declined rapidly after the use of zidovudine prophylaxis was recommended in 1994. In 2013, estimated incidence of perinatally acquired HIV infection in the United States was 1.8 (95% CI: 1.4 to 2.2), a 96% decline since the peak. CONCLUSION: Estimated incidence of perinatally acquired HIV infection in the United States in 2013 was 1.8/100,000 live births. PMID- 28991887 TI - Changes in Kidney Function Associated With Daily Tenofovir Disoproxil Fumarate/Emtricitabine for HIV Preexposure Prophylaxis Use in the United States Demonstration Project. AB - BACKGROUND: HIV preexposure prophylaxis (PrEP) using daily oral tenofovir disoproxil-fumarate/emtricitabine (TDF/FTC) is effective for preventing HIV acquisition, but concerns remain about its potential kidney toxicity. This study examined kidney function in individuals using PrEP in real-world clinical settings. SETTING: Demonstration project in 2 sexually transmitted infection clinics and a community health center. METHODS: We evaluated kidney function among men who have sex with men and transgender women taking tenofovir-disoproxil fumarate/emtricitabine PrEP for up to 48 weeks. Serum creatinine and urine dipstick for protein were obtained at 12-week intervals. Kidney function was estimated using creatinine clearance (CrCl) (Cockcroft-Gault) and estimated glomerular filtration rate (eGFR) (CKD-EPI). RESULTS: From October 2012 to January 2014, we enrolled 557 participants (median age 33). Mean creatinine increased from baseline to week 12 by 0.03 mg/dL (4.6%) (P < 0.0001); mean CrCl decreased by 4.8 mL/min (3.0%) (P < 0.0001). These changes remained stable through week 48 (P = 0.81, P = 0.71 respectively). There were 75/478 (15.7%) participants who developed worsening proteinuria at week 12 compared with baseline (P < 0.0001), and this percent remained stable through week 48 (P = 0.73). Twenty-five participants (5.1%) developed new-onset eGFR <70 mL/min/1.73 m; independent predictors of this outcome were age >=40 years (OR 3.79, 95% CI: 1.43 to 10.03) and baseline eGFR <90 mL/min/1.73 m (OR 9.59, 3.69-24.94). CONCLUSIONS: In a demonstration setting, daily tenofovir-disoproxil fumarate/emtricitabine PrEP leads to reduced CrCl and eGFR; however, these eGFR changes are based on very small changes in serum creatinine and seem to be nonprogressive after the first 12 weeks. Future studies are needed to understand the prognostic significance of these small changes. PMID- 28991889 TI - Trends in Drug Resistance Prevalence, HIV-1 Variants and Clinical Status in HIV-1 infected Pediatric Population in Madrid: 1993 to 2015 Analysis. AB - BACKGROUND: The expanded use of long-term antiretroviral treatments in infected children may exacerbate the problem of drug resistance mutations selection, which can compromise treatment efficiency. OBJECTIVE: We describe the temporal trends of HIV drug resistance mutations and the HIV-1 variants during 23 years (1993 to March 2016) in the Madrid cohort of HIV-infected children and adolescents. METHODS: We selected patients with at least one available HIV-1 pol sequence/genotypic resistance profile, establishing different groups according to the sampling year of first resistance data. We determined the prevalence of transmitted drug resistance mutations or acquired drug resistance mutations (DRM), the drug susceptibility among resistant viruses and HIV-1 variants characterized by phylogeny across time. RESULTS: A total of 245 pediatric patients were selected, being mainly female, Spanish native, perinatally infected and carrying HIV-1 subtype B. At first sampling, most pediatric patients were on antiretroviral therapy and heavily pretreated. During 1993 to 2016, transmitted drug resistance mutations was found in 13 (26%) of 50 naive children [non nucleoside reverse transcriptase inhibitors (NNRTI), 14.6%; nucleoside reverse transcriptase inhibitors (NRTI), 10.4%; protease inhibitors, 8.7%]. DRM appeared in 139 (73.2%) of 190 pretreated patients (NRTI, 64.5%; NNRTI, 36%; protease inhibitors, 35.1%). DRM to NNRTI was higher in last 5 years. Non-B variants infected 14.5% of children and adolescents of the Madrid Cohort, being mainly intersubtype recombinants (76.5%), including complex unique recombinant strains. They caused 3.4% infections before 2000, rising to 85.7% during 2011 to 2016. CONCLUSIONS: Periodic surveillance resistance and molecular epidemiology studies in long-term pretreated HIV-infected pediatric populations are required to optimize treatment regimens. Results will permit a better understanding of long time dynamics of viral resistance and HIV-1 variants in Spain. PMID- 28991888 TI - Commonly Prescribed Antiretroviral Therapy Regimens and Incidence of AIDS Defining Neurological Conditions. AB - BACKGROUND: The differential effects of commonly prescribed combined antiretroviral therapy (cART) regimens on AIDS-defining neurological conditions (neuroAIDS) remain unknown. SETTING: Prospective cohort studies of HIV-positive individuals from Europe and the Americas included in the HIV-CAUSAL Collaboration. METHODS: Individuals who initiated a first-line cART regimen in 2004 or later containing a nucleoside reverse transcriptase inhibitor backbone and either atazanavir, lopinavir, darunavir, or efavirenz were followed from cART initiation until death, lost to follow-up, pregnancy, the cohort-specific administrative end of follow-up, or the event of interest, whichever occurred earliest. We evaluated 4 neuroAIDS conditions: HIV dementia and the opportunistic infections toxoplasmosis, cryptococcal meningitis, and progressive multifocal leukoencephalopathy. For each outcome, we estimated hazard ratios for atazanavir, lopinavir, and darunavir compared with efavirenz via a pooled logistic model. Our models were adjusted for baseline demographic and clinical characteristics. RESULTS: Twenty six thousand one hundred seventy-two individuals initiated efavirenz, 5858 initiated atazanavir, 8479 initiated lopinavir, and 4799 initiated darunavir. Compared with efavirenz, the adjusted HIV dementia hazard ratios (95% confidence intervals) were 1.72 (1.00 to 2.96) for atazanavir, 2.21 (1.38 to 3.54) for lopinavir, and 1.41 (0.61 to 3.24) for darunavir. The respective hazard ratios (95% confidence intervals) for the combined end point were 1.18 (0.74 to 1.88) for atazanavir, 1.61 (1.14 to 2.27) for lopinavir, and 1.36 (0.74 to 2.48) for darunavir. The results varied in subsets defined by calendar year, nucleoside reverse transcriptase inhibitor backbone, and age. CONCLUSION: Our results are consistent with an increased risk of neuroAIDS after initiating lopinavir compared with efavirenz, but temporal changes in prescribing trends and confounding by indication could explain our findings. PMID- 28991890 TI - Delayed Diagnosis is Associated with Early and Emergency Need for First Crohn's Disease-Related Intestinal Surgery. AB - BACKGROUND Increasing evidence suggests that delayed diagnosis in Crohn's disease is associated with a complicated disease course. The aim of this study was to explore the association between delayed diagnosis and the timing of the first Crohn's disease-related intestinal surgery. MATERIAL AND METHODS A retrospective study included 215 Crohn's disease patients with previous surgical history in the Department of General Surgery of Jinling Hospital, China, between January 2013 and March 2016. Data were collected on demographics, clinical characteristics, medication history, and operation history. RESULTS The time from the first appearance of Crohn's disease-related symptoms to the first intestinal surgery in the delayed diagnosis group was obviously shorter than in the non-delayed diagnosis group (26.4+/-28.7 months vs. 42.6+/-58.4 months, respectively, p=0.032). Patients in the delayed diagnosis group tended to receive more ileal resections (47.8% vs. 26.4%, respectively, p=0.002) and less ileocecal resections (22.4% vs. 37.2%, respectively, p=0.032). More patients in the delayed diagnosis group received the first Crohn's disease-related intestinal surgery as an emergency one (20.9% vs. 4.7%, respectively, p=0.001). CONCLUSIONS Delayed diagnosis is associated with early and emergency need for the first Crohn's disease-related intestinal surgery. PMID- 28991891 TI - Achieving better-than-3-A resolution by single-particle cryo-EM at 200 keV. AB - Nearly all single-particle cryo-EM structures resolved to better than 4-A resolution have been determined using 300-keV transmission electron microscopes (TEMs). We demonstrate that it is possible to obtain reconstructions of macromolecular complexes of different sizes to better than 3-A resolution using a 200-keV TEM. These structures are of sufficient quality to unambiguously assign amino acid rotameric conformations and identify ordered water molecules. PMID- 28991892 TI - SCENIC: single-cell regulatory network inference and clustering. AB - We present SCENIC, a computational method for simultaneous gene regulatory network reconstruction and cell-state identification from single-cell RNA-seq data (http://scenic.aertslab.org). On a compendium of single-cell data from tumors and brain, we demonstrate that cis-regulatory analysis can be exploited to guide the identification of transcription factors and cell states. SCENIC provides critical biological insights into the mechanisms driving cellular heterogeneity. PMID- 28991893 TI - Treatment patterns and costs of care for patients with relapsed and refractory Hodgkin lymphoma treated with brentuximab vedotin in the United States: A retrospective cohort study. AB - OBJECTIVES: Although brentuximab vedotin (BV) has changed the management of patients with relapsed or refractory Hodgkin lymphoma (RRHL), little information is available on routine clinical practice. We identified treatment patterns and costs of care among RRHL patients in the United States (US) treated with BV. METHODS: A retrospective observational study of adults initiating BV for RRHL from 2011-2015, with >=6 months of data prior to and following BV initiation, was conducted. Treatments were classified based on dispensations and chemotherapy administration. Median total and monthly costs were estimated based on all-cause healthcare resource use in 2015 US dollars (USD). RESULTS: The cohort comprised 289 patients (59% male; mean age at diagnosis, 42 years) with a mean follow-up of 250 weeks. Eleven percent had BV salvage therapy prior to ASCT, and 32% had BV for a relapse post-ASCT. 43% received treatment post-BV, most commonly allogeneic stem cell transplant (SCT) and bendamustine (both 10.2%). Median (IQR) total costs from BV initiation to censoring were 294,790 (142,110-483,360) USD; and were highest among those treated with BV prior to ASCT (up to 421,900 [300,940 778,970] USD). Median monthly costs were almost 20,000 USD per month, and up to 25,000 USD per month among those with BV and ASCT. Medications were the greatest driver of median monthly costs. CONCLUSIONS: Median total all-cause costs were almost 300,000 USD, and median monthly costs approximately 20,000 USD, per patient treated. Patients requiring treatment following BV continue to incur high costs, highlighting the economic burden associated with managing patients in the RRHL setting. PMID- 28991894 TI - Sanitation, hookworm, anemia, stunting, and wasting in primary school children in southern Ethiopia: Baseline results from a study in 30 schools. AB - BACKGROUND: Inadequate nutrition; neglected topical diseases; and insufficient water, sanitation, and hygiene (WASH) are interrelated problems in schools in low income countries, but are not routinely tackled together. A recent three-year longitudinal study investigated integrated school health and nutrition approaches in 30 government primary schools in southern Ethiopia. Here, we report on baseline associations between sanitation, hookworm infection, anemia, stunting, and wasting. METHODS: In each school, the Schistosoma mansoni, S. haematobium, and soil-transmitted helminth infection intensities; blood hemoglobin concentrations; heights; and weights of approximately 125 students were assessed. Of these 125 students, approximately 20 were randomly selected for student WASH surveys. Of these 20, approximately 15 were randomly selected for household sanitation observations. School WASH was also assessed through a combination of observations and questions to the headteacher. Mixed-effects logistic regression was used to compare household sanitation with hookworm infection (the other parasites being much less prevalent); and hookworm infection with anemia, stunting, and wasting. FINDINGS: Blood, stool, and urine samples were provided by 3,729 children, and student WASH and household WASH surveys were conducted with 596 and 448 of these students, respectively. Hookworm, Ascaris lumbricoides, Trichuris trichiura, and S. mansoni infections had prevalences of 18%, 4.8%, 0.6%, and 0.3%, respectively, and no S. haematobium infections were found. Anemia, stunting, and wasting had prevalences of 23%, 28%, and 14%, respectively. No statistically significant associations were found between latrine absence or evidence of open defecation at home, and hookworm infection (adjusted odds ratio, OR = 1.28, 95% confidence interval, CI: 0.476-3.44; and adjusted OR = 1.21, 95% CI: 0.468-3.12; respectively); or between hookworm infection and anemia, stunting, or wasting (adjusted OR = 1.24, 95% CI: 0.988-1.57; adjusted OR = 0.992, 95% CI: 0.789-1.25; and adjusted OR = 0.969, 95% CI: 0.722-1.30; respectively). CONCLUSIONS: In this setting, no statistically significant associations were found between sanitation and hookworm; or between hookworm and anemia, stunting, or wasting. More evidence on best practices for integrated school health interventions will be gathered from the follow-up surveys in this study. PMID- 28991895 TI - Multi-site cholera surveillance within the African Cholera Surveillance Network shows endemicity in Mozambique, 2011-2015. AB - BACKGROUND: Mozambique suffers recurrent annual cholera outbreaks especially during the rainy season between October to March. The African Cholera Surveillance Network (Africhol) was implemented in Mozambique in 2011 to generate accurate detailed surveillance data to support appropriate interventions for cholera control and prevention in the country. METHODOLOGY/PRINCIPAL FINDINGS: Africhol was implemented in enhanced surveillance zones located in the provinces of Sofala (Beira), Zambezia (District Mocuba), and Cabo Delgado (Pemba City). Data were also analyzed from the three outbreak areas that experienced the greatest number of cases during the time period under observation (in the districts of Cuamba, Montepuez, and Nampula). Rectal swabs were collected from suspected cases for identification of Vibrio cholerae, as well as clinical, behavioral, and socio-demographic variables. We analyzed factors associated with confirmed, hospitalized, and fatal cholera using multivariate logistic regression models. A total of 1,863 suspected cases and 23 deaths (case fatality ratio (CFR), 1.2%) were reported from October 2011 to December 2015. Among these suspected cases, 52.2% were tested of which 23.5% were positive for Vibrio cholerae O1 Ogawa. Risk factors independently associated with the occurrence of confirmed cholera were living in Nampula city district, the year 2014, human immunodeficiency virus infection, and the primary water source for drinking. CONCLUSIONS/SIGNIFICANCE: Cholera was endemic in Mozambique during the study period with a high CFR and identifiable risk factors. The study reinforces the importance of continued cholera surveillance, including a strong laboratory component. The results enhanced our understanding of the need to target priority areas and at-risk populations for interventions including oral cholera vaccine (OCV) use, and assess the impact of prevention and control strategies. Our data were instrumental in informing integrated prevention and control efforts during major cholera outbreaks in recent years. PMID- 28991896 TI - T-cell regulation in Erythema Nodosum Leprosum. AB - Leprosy is a disease caused by Mycobacterium leprae where the clinical spectrum correlates with the patient immune response. Erythema Nodosum Leprosum (ENL) is an immune-mediated inflammatory complication, which causes significant morbidity in affected leprosy patients. The underlying cause of ENL is not conclusively known. However, immune-complexes and cell-mediated immunity have been suggested in the pathogenesis of ENL. The aim of this study was to investigate the regulatory T-cells in patients with ENL. Forty-six untreated patients with ENL and 31 non-reactional lepromatous leprosy (LL) patient controls visiting ALERT Hospital, Ethiopia were enrolled to the study. Blood samples were obtained before, during and after prednisolone treatment of ENL cases. Peripheral blood mononuclear cells (PBMCs) were isolated and used for immunophenotyping of regulatory T-cells by flow cytometry. Five markers: CD3, CD4 or CD8, CD25, CD27 and FoxP3 were used to define CD4+ and CD8+ regulatory T-cells. Clinical and histopathological data were obtained as supplementary information. All patients had been followed for 28 weeks. Patients with ENL reactions had a lower percentage of CD4+ regulatory T-cells (1.7%) than LL patient controls (3.8%) at diagnosis of ENL before treatment. After treatment, the percentage of CD4+regulatory T-cells was not significantly different between the two groups. The percentage of CD8+ regulatory T-cells was not significantly different in ENL and LL controls before and after treatment. Furthermore, patients with ENL had higher percentage of CD4+ T-ells and CD4+/CD8+ T-cells ratio than LL patient controls before treatment. The expression of CD25 on CD4+ and CD8+ T-cells was not significantly different in ENL and LL controls suggesting that CD25 expression is not associated with ENL reactions while FoxP3 expression on CD4+ T cells was significantly lower in patients with ENL than in LL controls. We also found that prednisolone treatment of patients with ENL reactions suppresses CD4+ T-cell but not CD8+ T-cell frequencies. Hence, ENL is associated with lower levels of T regulatory cells and higher CD4+/CD8+ T-cell ratio. We suggest that this loss of regulation is one of the causes of ENL. PMID- 28991897 TI - The influence of different diets on metabolism and atherosclerosis processes-A porcine model: Blood serum, urine and tissues 1H NMR metabolomics targeted analysis. AB - The global epidemic of cardiovascular diseases leads to increased morbidity and mortality caused mainly by myocardial infarction and stroke. Atherosclerosis is the major pathological process behind this epidemic. We designed a novel model of atherosclerosis in swine. Briefly, the first group (11 pigs) received normal pig feed (balanced diet group-BDG) for 12 months, the second group (9 pigs) was fed a Western high-calorie diet (unbalanced diet group-UDG) for 12 months, the third group (8 pigs) received a Western type high-calorie diet for 9 months later replaced by a normal diet for 3 months (regression group-RG). Clinical measurements included zoometric data, arterial blood pressure, heart rate and ultrasonographic evaluation of femoral arteries. Then, the animals were sacrificed and the blood serum, urine and skeletal muscle tissue were collected and 1H NMR based metabolomics studies with the application of fingerprinting PLS DA and univariate analysis were done. Our results have shown that the molecular disturbances might overlap with other diseases such as onset of diabetes, sleep apnea and other obesity accompanied diseases. Moreover, we revealed that once initiated, molecular changes did not return to homeostatic equilibrium, at least for the duration of this experiment. PMID- 28991898 TI - Insights and efforts to control rabies in Zambia: Evaluation of determinants and barriers to dog vaccination in Nyimba district. AB - BACKGROUND: The current rabies control strategy in Zambia is based on dog vaccination, dog population control and dog movement restrictions. In Nyimba district of Zambia, dog vaccination coverage is low but the incidence of dog bites is high which places the community at risk of rabies infection. The renewed global interest eliminating rabies in developing countries has spurred interest to identify determinants and barriers of dog vaccination in an effort to reduce the overall disease burden. METHODOLOGY: A mixed methods cross sectional design was used in the study. This consisted of three parts: Evaluation of medical records regarding dog bite injuries, implementation and analysis of a household survey and in-depth review of key informant interviews. Data was collected into a Microsoft Excel database and subsequently transferred to STATA for descriptive, inferential and thematic analysis. RESULTS: Dog vaccination coverage overall was 8.7% (57/655), with 3.4% (22/655) in urban areas, 1.8% (12/655) in peri-urban and 3.5 (23/655) in the rural regions. Financially stable households were more likely to have their dogs vaccinated. Only 10.3% (31/300) of the respondents had vaccinated their dogs and these had a reliable source of income as 6% (18/300) were peasant farmers, 2% (6/300) were dependants whose guardians were financially stable and 2.3% (7/300) were in steady employment. Important barriers to dog vaccination included cost, limited awareness of vaccination program and access. CONCLUSION: Current rabies control strategies in Nyimba district, Zambia, appear quite limited. Improvements in the regional dog vaccination program may provide benefits. Enhancement of educational efforts targeting behavioural factors may also prove useful. Finally, the cost of dog vaccination can be reduced with scaled up production of a local vaccine. PMID- 28991899 TI - Albendazole and ivermectin for the control of soil-transmitted helminths in an area with high prevalence of Strongyloides stercoralis and hookworm in northwestern Argentina: A community-based pragmatic study. AB - BACKGROUND: Recommendations for soil-transmitted helminth (STH) control give a key role to deworming of school and pre-school age children with albendazole or mebendazole; which might be insufficient to achieve adequate control, particularly against Strongyloides stercoralis. The impact of preventive chemotherapy (PC) against STH morbidity is still incompletely understood. The aim of this study was to assess the effectiveness of a community-based program with albendazole and ivermectin in a high transmission setting for S. stercoralis and hookworm. METHODOLOGY: Community-based pragmatic trial conducted in Tartagal, Argentina; from 2012 to 2015. Six communities (5070 people) were enrolled for community-based PC with albendazole and ivermectin. Two communities (2721 people) were re-treated for second and third rounds. STH prevalence, anemia and malnutrition were explored through consecutive surveys. Anthropometric assessment of children, stool analysis, complete blood count and NIE-ELISA serology for S. stercoralis were performed. PRINCIPAL FINDINGS: STH infection was associated with anemia and stunting in the baseline survey that included all communities and showed a STH prevalence of 47.6% (almost exclusively hookworm and S. stercoralis). Among communities with multiple interventions, STH prevalence decreased from 62% to 23% (p<0.001) after the first PC; anemia also diminished from 52% to 12% (p<0.001). After two interventions S. stercoralis seroprevalence declined, from 51% to 14% (p<0.001) and stunting prevalence decreased, from 19% to 12% (p = 0.009). CONCLUSIONS: Hookworm' infections are associated with anemia in the general population and nutritional impairment in children. S. stercoralis is also associated with anemia. Community-based deworming with albendazole and ivermectin is effective for the reduction of STH prevalence and morbidity in communities with high prevalence of hookworm and S. stercoralis. PMID- 28991900 TI - Intra-individual variability and circadian rhythm of vascular endothelial growth factors in subjects with normal glucose tolerance and type 2 diabetes. AB - : Increased levels of systemic vascular endothelial growth factors (VEGFs) in patients with diabetes are associated with increased risk of microvessel disease. On the other hand, low VEGF levels after intravitreal antibody application may be associated with acute cardiovascular complications and treatment failure. Individual levels of systemic VEGF vary in a wide range depending on analytical methods and quality of diabetes control. So far only limited information exists on intraindividual fluctuations over longer periods and circadian rhythms. We analysed the intraindividual variance of VEGF-A, VEGF-C and placental growth factor (PLGF) in CTAD (citrate-theophylline-adenine-dipyridamol) plasma as well as VEGF-A in serum over a period of 6 months in patients with stable controlled type 2 diabetes (10 M, 10 F) and age and sex matched subjects with normal glucose tolerance (NGT). Furthermore, circadian levels of VEGFs were controlled hourly from 7:30 a.m. to 7:30 p.m. under standardized metabolic ward conditions. In addition, the relationship to metabolic, hormonal and inflammatory biomarkers was analyzed. VEGF-A, VEGF-C and PLGF remained stable in plasma and VEGF-A in serum over 6 months in both groups. No circadian change was observed in VEGF-A serum and plasma concentrations. A minor decrease of VEGF-C plasma levels was evident after 5 p.m. in both groups and a significant peak of PLGF concentrations occurred after lunch, which was more pronounced in T2DM. In multivariate analysis, only serum VEGF-A correlated to diabetes duration, whereas VEGF-C only correlated to HbA1c and fasting blood glucose. We did not observe significant intraindividual variances for VEGF-A in serum and VEGF-A, VEGF-C and PLGF in CTAD plasma over a period of 6 months. Taken together, a single morning measurement of systemic VEGF levels after 7:30 am appears to be a reliable parameter for the individual risk associated with abnormal VEGF concentrations in blood. TRIAL REGISTRATION: NCT02325271. PMID- 28991901 TI - The blue light-induced interaction of cryptochrome 1 with COP1 requires SPA proteins during Arabidopsis light signaling. AB - Plants constantly adjust their growth, development and metabolism to the ambient light environment. Blue light is sensed by the Arabidopsis photoreceptors CRY1 and CRY2 which subsequently initiate light signal transduction by repressing the COP1/SPA E3 ubiquitin ligase. While the interaction between cryptochromes and SPA is blue light-dependent, it was proposed that CRY1 interacts with COP1 constitutively, i.e. also in darkness. Here, our in vivo co-immunoprecipitation experiments suggest that CRY1 and CRY2 form a complex with COP1 only after seedlings were exposed to blue light. No association between COP1 and CRY1 or CRY2 was observed in dark-grown seedlings. Thus, our results suggest that cryptochromes bind the COP1/SPA complex after photoactivation by blue light. In a spa quadruple mutant that is devoid of all four SPA proteins, CRY1 and COP1 did not interact in vivo, neither in dark-grown nor in blue light-grown seedlings. Hence, SPA proteins are required for the high-affinity interaction between CRY1 and COP1 in blue light. Yeast three-hybrid experiments also show that SPA1 enhances the CRY1-COP1 interaction. The coiled-coil domain of SPA1 which is responsible for COP1-binding was necessary to mediate a CRY1-SPA1 interaction in vivo, implying that-in turn-COP1 may be necessary for a CRY1-SPA1 complex formation. Hence, SPA1 and COP1 may act cooperatively in recognizing and binding photoactivated CRY1. In contrast, the blue light-induced association between CRY2 and COP1 was not dependent on SPA proteins in vivo. Similarly, DeltaCC-SPA1 interacted with CRY2, though with a much lower affinity than wild-type SPA1. In total, our results demonstrate that CRY1 and CRY2 strongly differ in their blue light-induced interaction with the COP1/SPA complex. PMID- 28991902 TI - How does competition among wild type mosquitoes influence the performance of Aedes aegypti and dissemination of Wolbachia pipientis? AB - BACKGROUND: Wolbachia has been deployed in several countries to reduce transmission of dengue, Zika and chikungunya viruses. During releases, Wolbachia infected females are likely to lay their eggs in local available breeding sites, which might already be colonized by local Aedes sp. mosquitoes. Therefore, there is an urgent need to estimate the deleterious effects of intra and interspecific larval competition on mosquito life history traits, especially on the duration of larval development time, larval mortality and adult size. METHODOLOGY/PRINCIPAL FINDINGS: Three different mosquito populations were used: Ae. aegypti infected with Wolbachia (wMelBr strain), wild Ae. aegypti and wild Ae. albopictus. A total of 21 treatments explored intra and interspecific larval competition with varying larval densities, species proportions and food levels. Each treatment had eight replicates with two distinct food levels: 0.25 or 0.50 g of Chitosan and fallen avocado leaves. Overall, overcrowding reduced fitness correlates of the three populations. Ae. albopictus larvae presented lower larval mortality, shorter development time to adult and smaller wing sizes than Ae. aegypti. The presence of Wolbachia had a slight positive effect on larval biology, since infected individuals had higher survivorship than uninfected Ae. aegypti larvae. CONCLUSIONS/SIGNIFICANCE: In all treatments, Ae. albopictus outperformed both wild Ae. aegypti and the Wolbachia-infected group in larval competition, irrespective of larval density and the amount of food resources. The major force that can slow down Wolbachia invasion is the population density of wild mosquitoes. Given that Ae. aegypti currently dominates in Rio, in comparison with Ae. albopictus frequency, additional attention must be given to the population density of Ae. aegypti during releases to increase the likelihood of Wolbachia invasion. PMID- 28991903 TI - The effect of electronic monitoring feedback on medication adherence and clinical outcomes: A systematic review. AB - OBJECTIVE: This study aims to assess the efficacy of Electronic Monitoring Feedback (EMF) as an intervention to improve medication adherence (i.e. dose- or full adherence) and clinical outcomes in adult patients. METHODS: A systematic search was performed in Medline, EMBASE, PsycINFO and Web of Science and reported according to the PRISMA guidelines. Randomised controlled trials (RCTs) comparing EMF with usual care were identified to systematically summarise the evidence for use of EMF in improving medication adherence and clinical outcomes. The GRADE approach was used to assess the quality of the body of evidence. RESULTS: Of 9,993 initially-identified studies, ten studies (four of high-quality and six of low-quality) were included. The sample size of the studies included varied from 18 to 205 patients. Four of the six studies (66.7%) reported a significant positive effect of EMF on mean dose adherence levels, whereas a significant positive effect of EMF on mean full adherence levels was found in all of the included studies (100%, five out of five of the studies included). A significant positive effect of EMF on clinical outcomes was reported in one of the seven studies included. The overall effect of EMF on mean dose- and full adherence was positive and the overall effect of EMF on clinical outcomes was inconclusive. CONCLUSION: Considering the positive effect of EMF on medication adherence, EMF might be a promising intervention to enhance medication adherence. However, the effect of EMF on clinical outcomes was inconclusive. Prior to implementing EMF in clinical practice, future research with high-quality studies (e.g. adequate sample sizes, follow-up periods and no interfering co-interventions) is required to examine the (long-term) efficacy of EMF. PMID- 28991904 TI - Epidemiological consequences of immune sensitisation by pre-exposure to vector saliva. AB - Blood-feeding arthropods-like mosquitoes, sand flies, and ticks-transmit many diseases that impose serious public health and economic burdens. When a blood feeding arthropod bites a mammal, it injects saliva containing immunogenic compounds that facilitate feeding. Evidence from Leishmania, Plasmodium and arboviral infections suggests that the immune responses elicited by pre-exposure to arthropod saliva can alter disease progression if the host later becomes infected. Such pre-sensitisation of host immunity has been reported to both exacerbate and limit infection symptoms, depending on the system in question, with potential implications for recovery. To explore if and how immune pre sensitisation alters the effects of vector control, we develop a general model of vector-borne disease. We show that the abundance of pre-sensitised infected hosts should increase when control efforts moderately increase vector mortality rates. If immune pre-sensitisation leads to more rapid clearance of infection, increasing vector mortality rates may achieve greater than expected disease control. However, when immune pre-sensitisation prolongs the duration of infection, e.g., through mildly symptomatic cases for which treatment is unlikely to be sought, vector control can actually increase the total number of infected hosts. The rising infections may go unnoticed unless active surveillance methods are used to detect such sub-clinical individuals, who could provide long-lasting reservoirs for transmission and suffer long-term health consequences of those sub clinical infections. Sensitivity analysis suggests that these negative consequences could be mitigated through integrated vector management. While the effect of saliva pre-exposure on acute symptoms is well-studied for leishmaniasis, the immunological and clinical consequences are largely uncharted for other vector-parasite-host combinations. We find a large range of plausible epidemiological outcomes, positive and negative for public health, underscoring the need to quantify how immune pre-sensitisation modulates recovery and transmission rates in vector-borne diseases. PMID- 28991905 TI - The presence and severity of cerebral small vessel disease increases the frequency of stroke in a cohort of patients with large artery occlusive disease. AB - BACKGROUND: Cerebral small vessel disease (SVD) commonly coexists with large artery atherosclerosis (LAA). AIM: We evaluate the effect of SVD on stroke recurrence in patients for ischemic stroke with LAA. METHODS: We consecutively collected first-ever ischemic stroke patients who were classified as LAA mechanism between Jan 2010 and Dec 2013. Univariate and multivariate Cox analyses were performed to evaluate the association between the 2-year recurrence and demographic, clinical, and radiological factors. To evaluate the impact of SVD and its components on recurrent stroke, we used the Kaplan-Meier analysis. SVD was defined as the presence of severe white matter hyperintensity (WMH) or old lacunar infarction (OLI) or cerebral microbleeds (CMB). We also compared frequency and burden of SVD among recurrent stroke groups with different mechanisms. RESULTS: Among a total of 956 participants, 92 patients had recurrent events. Recurrence group showed a higher frequency of severe WMH, OLI, asymptomatic territorial infarction, and severe stenosis on the relevant vessel in multivariate analysis. The impact of SVD and its components on recurrent stroke was significant in any ischemic recurrent stroke, and the presence of SVD was continuously important in stroke recurrence regardless of its mechanism, including recurrent LAA stroke, recurrent small vessel occlusion stroke, and even recurrent cardioembolic stroke. Additionally, the recurrence rate increased in dose-response manner with the increased number of SVD components. CONCLUSIONS: Cerebral SVD is associated with recurrent stroke in patients with LAA. Additionally, it may affect any mechanisms of recurrent stroke and even with a dose response manner. PMID- 28991906 TI - Object detection through search with a foveated visual system. AB - Humans and many other species sense visual information with varying spatial resolution across the visual field (foveated vision) and deploy eye movements to actively sample regions of interests in scenes. The advantage of such varying resolution architecture is a reduced computational, hence metabolic cost. But what are the performance costs of such processing strategy relative to a scheme that processes the visual field at high spatial resolution? Here we first focus on visual search and combine object detectors from computer vision with a recent model of peripheral pooling regions found at the V1 layer of the human visual system. We develop a foveated object detector that processes the entire scene with varying resolution, uses retino-specific object detection classifiers to guide eye movements, aligns its fovea with regions of interest in the input image and integrates observations across multiple fixations. We compared the foveated object detector against a non-foveated version of the same object detector which processes the entire image at homogeneous high spatial resolution. We evaluated the accuracy of the foveated and non-foveated object detectors identifying 20 different objects classes in scenes from a standard computer vision data set (the PASCAL VOC 2007 dataset). We show that the foveated object detector can approximate the performance of the object detector with homogeneous high spatial resolution processing while bringing significant computational cost savings. Additionally, we assessed the impact of foveation on the computation of bottom-up saliency. An implementation of a simple foveated bottom-up saliency model with eye movements showed agreement in the selection of top salient regions of scenes with those selected by a non-foveated high resolution saliency model. Together, our results might help explain the evolution of foveated visual systems with eye movements as a solution that preserves perceptual performance in visual search while resulting in computational and metabolic savings to the brain. PMID- 28991907 TI - Effects of the Healthy Start randomized intervention trial on physical activity among normal weight preschool children predisposed to overweight and obesity. AB - BACKGROUND: There is limited evidence to support the effectiveness of primary interventions aiming to prevent excess weight gain among young children. Evaluating behavioral changes, such as physical activity (PA), may add to future development of efficient interventions. The objective was to evaluate the effect on PA outcomes of the 15 month Healthy Start intervention that focused on changing diet, PA, sleep and stress management among normal weight but obesity prone preschool children. Children were defined as obesity-prone if they had a birth weight > 4,000 g, mothers with a pre-pregnancy body mass index of > 28 kg/m2, or mothers with <= 10 years of schooling. METHOD: From a baseline study population of 635 normal weight 2-6 year old preschool children from the greater Copenhagen area, parents of 307 children had given information on PA at both the baseline and follow-up examinations. PA was obtained from a 7 days recording in the Children's Physical Activity Questionnaire. Time used for sport activities were combined with outdoor playing time to achieve a proxy of total PA level of moderate to vigorous intensity. RESULTS: Linear regression analyses revealed that at follow-up the intervention group spent more time on sports and outdoor activities combined per week than the control group (ITT analyses: intervention: 400 min/week; 95% confidence interval (CI): 341, 459 versus control: 321 min/week; 95% CI: 277, 366; p = 0.02), although no significant intervention effects were seen for each of the subcategories, e.g. sports participation, outdoor activities, screen time, or commuting frequency. CONCLUSION: Our results suggest that the overall time spent on sports and outdoor activities combined was increased at follow-up among normal weight obesity-prone children, as a result of the Healthy Start intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT01583335. PMID- 28991908 TI - Mitochondrial dual-coding genes in Trypanosoma brucei. AB - Trypanosoma brucei is transmitted between mammalian hosts by the tsetse fly. In the mammal, they are exclusively extracellular, continuously replicating within the bloodstream. During this stage, the mitochondrion lacks a functional electron transport chain (ETC). Successful transition to the fly, requires activation of the ETC and ATP synthesis via oxidative phosphorylation. This life cycle leads to a major problem: in the bloodstream, the mitochondrial genes are not under selection and are subject to genetic drift that endangers their integrity. Exacerbating this, T. brucei undergoes repeated population bottlenecks as they evade the host immune system that would create additional forces of genetic drift. These parasites possess several unique genetic features, including RNA editing of mitochondrial transcripts. RNA editing creates open reading frames by the guided insertion and deletion of U-residues within the mRNA. A major question in the field has been why this metabolically expensive system of RNA editing would evolve and persist. Here, we show that many of the edited mRNAs can alter the choice of start codon and the open reading frame by alternative editing of the 5' end. Analyses of mutational bias indicate that six of the mitochondrial genes may be dual-coding and that RNA editing allows access to both reading frames. We hypothesize that dual-coding genes can protect genetic information by essentially hiding a non-selected gene within one that remains under selection. Thus, the complex RNA editing system found in the mitochondria of trypanosomes provides a unique molecular strategy to combat genetic drift in non-selective conditions. PMID- 28991909 TI - Prevalence, intensity and risk factors of tungiasis in Kilifi County, Kenya: I. Results from a community-based study. AB - BACKGROUND: Tungiasis is a neglected tropical disease caused by female sand fleas (Tunga penetrans) embedded in the skin. The disease is associated with important morbidity. Tungiasis is endemic along the Coast of Kenya with a prevalence ranging from 11% to 50% in school-age children. Hitherto, studies on epidemiological characteristics of tungiasis in Africa are scanty. METHODS: In a cross-sectional study 1,086 individuals from 233 households in eight villages located in Kakuyuni and Malanga Sub-locations, Kilifi County, on the Kenyan Coast, were investigated. Study participants were examined systematically and the presence and severity of tungiasis were determined using standard methods. Demographic, socio-economic, environmental and behavioral risk factors of tungiasis were assessed using a structured questionnaire. Data were analyzed using bivariate and multivariate regression analysis. RESULTS: The overall prevalence of tungiasis was 25.0% (95% CI 22.4-27.5%). Age-specific prevalence followed an S-shaped curve, peaking in the under-15 year old group. In 42.5% of the households at least one individual had tungiasis. 15.1% of patients were severely infected (>= 30 lesions). In the bivariate analysis no specific animal species was identified as a risk factor for tungiasis. Multivariate analysis showed that the occurrence of tungiasis was related to living in a house with poor construction characteristics, such as mud walls (OR 3.35; 95% CI 1.71-6.58), sleeping directly on the floor (OR 1.68; 95% CI 1.03-2.74), the number of people per sleeping room (OR = 1.77; 95% CI 1.07-2.93) and washing the body without soap (OR = 7.36; 95% CI 3.08-17.62). The odds of having severe tungiasis were high in males (OR 2.29; 95% CI 1.18-44.6) and were very high when only mud puddles were available as a water source and lack of water permitted washing only once a day (OR 25.48 (95% CI 3.50-185.67) and OR 2.23 (95% CI 1.11-4.51), respectively). CONCLUSIONS: The results of this study show that in rural Kenya characteristics of poverty determine the occurrence and the severity of tungiasis. Intra domiciliary transmission seems to occur regularly. PMID- 28991910 TI - Loss of Xist RNA from the inactive X during B cell development is restored in a dynamic YY1-dependent two-step process in activated B cells. AB - X-chromosome inactivation (XCI) in female lymphocytes is uniquely regulated, as the inactive X (Xi) chromosome lacks localized Xist RNA and heterochromatin modifications. Epigenetic profiling reveals that Xist RNA is lost from the Xi at the pro-B cell stage and that additional heterochromatic modifications are gradually lost during B cell development. Activation of mature B cells restores Xist RNA and heterochromatin to the Xi in a dynamic two-step process that differs in timing and pattern, depending on the method of B cell stimulation. Finally, we find that DNA binding domain of YY1 is necessary for XCI in activated B cells, as ex-vivo YY1 deletion results in loss of Xi heterochromatin marks and up regulation of X-linked genes. Ectopic expression of the YY1 zinc finger domain is sufficient to restore Xist RNA localization during B cell activation. Together, our results indicate that Xist RNA localization is critical for maintaining XCI in female lymphocytes, and that chromatin changes on the Xi during B cell development and the dynamic nature of YY1-dependent XCI maintenance in mature B cells predisposes X-linked immunity genes to reactivation. PMID- 28991911 TI - Associations between an IgG3 polymorphism in the binding domain for FcRn, transplacental transfer of malaria-specific IgG3, and protection against Plasmodium falciparum malaria during infancy: A birth cohort study in Benin. AB - BACKGROUND: Transplacental transfer of maternal immunoglobulin G (IgG) to the fetus helps to protect against malaria and other infections in infancy. Recent studies have emphasized the important role of malaria-specific IgG3 in malaria immunity, and its transfer may reduce the risk of malaria in infancy. Human IgGs are actively transferred across the placenta by binding the neonatal Fc receptor (FcRn) expressed within the endosomes of the syncytiotrophoblastic membrane. Histidine at position 435 (H435) provides for optimal Fc-IgG binding. In contrast to other IgG subclasses, IgG3 is highly polymorphic and usually contains an arginine at position 435, which reduces its binding affinity to FcRn in vitro. The reduced binding to FcRn is associated with reduced transplacental transfer and reduced half-life of IgG3 in vivo. Some haplotypes of IgG3 have histidine at position 435. This study examines the hypotheses that the IgG3-H435 variant promotes increased transplacental transfer of malaria-specific antibodies and a prolonged IgG3 half-life in infants and that its presence correlates with protection against clinical malaria during infancy. METHODS AND FINDINGS: In Benin, 497 mother-infant pairs were included in a longitudinal birth cohort. Both maternal and cord serum samples were assayed for levels of IgG1 and IgG3 specific for MSP119, MSP2 (both allelic families, 3D7 and FC27), MSP3, GLURP (both regions, R0 and R2), and AMA1 antigens of Plasmodium falciparum. Cord:maternal ratios were calculated. The maternal IgG3 gene was sequenced to identify the IgG3 H435 polymorphism. A multivariate logistic regression was used to examine the association between maternal IgG3-H435 polymorphism and transplacental transfer of IgG3, adjusting for hypergammaglobulinemia, maternal malaria, and infant malaria exposure. Twenty-four percent of Beninese women living in an area highly endemic for malaria had the IgG3-H435 allele (377 women homozygous for the IgG3 R435 allele, 117 women heterozygous for the IgG3-R/H alleles, and 3 women homozygous for the IgG3-H435 allele). Women with the IgG3-H435 allele had a 78% (95% CI 17%, 170%, p = 0.007) increased transplacental transfer of GLURP-R2 IgG3 compared to those without the IgG3-H435 allele. Furthermore, in infants born to mothers with the IgG3-H435 variant, a 28% longer IgG3 half-life was noted (95% CI 4%, 59%, p = 0.02) compared to infants born to mothers homozygous for the IgG3 R435 allele. Similar findings were observed for AMA1, MSP2-3D7, MSP3, GLURP-R0, and GLURP-R2 but not for MSP119 and MSP2-FC27. Infants born to women with IgG3 H435 had a 32% lower risk of symptomatic malaria during infancy (incidence rate ratio [IRR] = 0.68 [95% CI 0.51, 0.91], p = 0.01) compared to infants born to mothers homozygous for IgG3-R435. We did not find a lower risk of asymptomatic malaria in infants born to women with or without IgG3-H435. Limitations of the study were the inability to determine (i) the actual amount of IgG3-H435 relative to IgG-R435 in serum samples and (ii) the proportion of malaria-specific IgG produced by infants versus acquired from their mothers. CONCLUSIONS: An arginine to-histidine replacement at residue 435 in the binding domain of IgG3 to FcRn increases the transplacental transfer and half-life of malaria-specific IgG3 in young infants and is associated with reduced risk of clinical malaria during infancy. The IgG3-H435 allele may be under positive selection, given its relatively high frequency in malaria endemic areas. PMID- 28991912 TI - The CodY-dependent clhAB2 operon is involved in cell shape, chaining and autolysis in Bacillus cereus ATCC 14579. AB - The Gram-positive pathogen Bacillus cereus is able to grow in chains of rod shaped cells, but the regulation of chaining remains largely unknown. Here, we observe that glucose-grown cells of B. cereus ATCC 14579 form longer chains than those grown in the absence of glucose during the late exponential and transition growth phases, and identify that the clhAB2 operon is required for this chain lengthening phenotype. The clhAB2 operon is specific to the B. cereus group (i.e., B. thuringiensis, B. anthracis and B. cereus) and encodes two membrane proteins of unknown function, which are homologous to the Staphylococcus aureus CidA and CidB proteins involved in cell death control within glucose-grown cells. A deletion mutant (DeltaclhAB2) was constructed and our quantitative image analyses show that DeltaclhAB2 cells formed abnormal short chains regardless of the presence of glucose. We also found that glucose-grown cells of DeltaclhAB2 were significantly wider than wild-type cells (1.47 MUm +/-CI95% 0.04 vs 1.19 MUm +/-CI95% 0.03, respectively), suggesting an alteration of the bacterial cell wall. Remarkably, DeltaclhAB2 cells showed accelerated autolysis under autolysis inducing conditions, compared to wild-type cells. Overall, our data suggest that the B. cereus clhAB2 operon modulates peptidoglycan hydrolase activity, which is required for proper cell shape and chain length during cell growth, and down regulates autolysin activity. Lastly, we studied the transcription of clhAB2 using a lacZ transcriptional reporter in wild-type, ccpA and codY deletion-mutant strains. We found that the global transcriptional regulatory protein CodY is required for the basal level of clhAB2 expression under all conditions tested, including the transition growth phase while CcpA, the major global carbon regulator, is needed for the high-level expression of clhAB2 in glucose-grown cells. PMID- 28991913 TI - Diagnosis disclosure to adolescents living with HIV in rural Kenya improves antiretroviral therapy adherence and immunologic outcomes: A retrospective cohort study. AB - BACKGROUND & AIMS: Emphasis on adolescent HIV has increased worldwide as antiretroviral treatment has greatly extended life expectancies of HIV-positive children. Few evidence-based guidelines exist on the optimal time to disclose to an adolescent living with HIV (ALHIV); little is known about the medical effects of disclosure. This study looked to determine whether disclosure is associated with improved medical outcomes in ALHIV. Prior work has tended to be qualitative, cross-sectional, and with an emphasis on psychosocial outcomes. This paper addresses the adolescent cohort retrospectively (longitudinally), building upon what is already known about disclosure. METHODS: Retrospective, longitudinal clinical record reviews of ALHIV seen at Kericho District Hospital between April 2004 and November 2012 were performed. Patient demographics and clinical outcomes were systematically extracted. The student's t-test was used to calculate changes in mean CD4 count, antiretroviral therapy (ART), and cotrimoxazole adherence pre- vs. post-disclosure. Linear regression modelling assessed for trends in those clinical outcomes associated with age of disclosure. RESULTS: Ninety-six ALHIV (54 female, 42 male) were included; most (73%) entered care through the outpatient department. Nearly half were cared for by parents, and 20% experienced a change in their primary caregiver. The mean time in the study was 2.47 years; mean number of visits 10.97 per patient over the mean time in the study. Mean disclosure age was 12.34 years. An increase in mean ART adherence percentage was found with disclosure (0.802 vs. 0.917; p = 0.0015). Younger disclosure age was associated with significantly higher mean CD4 counts over the course of the study (p = 0.001), and a nonsignificant trend toward a higher mean ART adherence percentage (p = 0.055). CONCLUSION: ART adherence and improved immunologic status are both associated with disclosure of HIV infection to adolescent patients. Disclosure of an HIV diagnosis to an adolescent is an important means to improve HIV care. PMID- 28991915 TI - Analysing published global Ebola Virus Disease research using social network analysis. AB - INTRODUCTION: The 2014/2015 West African Ebola Virus Disease (EVD) outbreak attracted global attention. Numerous opinions claimed that the global response was impaired, in part because, the EVD research was neglected, although quantitative or qualitative studies did not exist. Our objective was to analyse how the EVD research landscape evolved by exploring the existing research network and its communities before and during the outbreak in West Africa. METHODS/ PRINCIPAL FINDINGS: Social network analysis (SNA) was used to analyse collaborations between institutions named by co-authors as affiliations in publications on EVD. Bibliometric data of publications on EVD between 1976 and 2015 was collected from Thomson Reuters' Web of Science Core Collection (WoS). Freely available software was used for network analysis at a global-level and for 10-year periods. The networks are presented as undirected-weighted graphs. Rankings by degree and betweenness were calculated to identify central and powerful network positions; modularity function was used to identify research communities. Overall 4,587 publications were identified, of which 2,528 were original research articles. Those yielded 1,644 authors' affiliated institutions and 9,907 connections for co-authorship network construction. The majority of institutions were from the USA, Canada and Europe. Collaborations with research partners on the African continent did exist, but less frequently. Around six highly connected organisations in the network were identified with powerful and broker positions. Network characteristics varied widely among the 10-year periods and evolved from 30 to 1,489 institutions and 60 to 9,176 connections respectively. Most influential actors are from public or governmental institutions whereas private sector actors, in particular the pharmaceutical industry, are largely absent. CONCLUSION/ SIGNIFICANCE: Research output on EVD has increased over time and surged during the 2014/2015 outbreak. The overall EVD research network is organised around a few key actors, signalling a concentration of expertise but leaving room for increased cooperation with other institutions especially from affected countries. Finding innovative ways to maintain support for these pivotal actors while steering the global EVD research network towards an agenda driven by agreed, prioritized needs and finding ways to better integrate currently peripheral and newer expertise may accelerate the translation of research into the development of necessary live saving products for EVD ahead of the next outbreak. PMID- 28991914 TI - Topiramate modulates trigeminal pain processing in thalamo-cortical networks in humans after single dose administration. AB - Migraine is the sixth most common cause of disability in the world. Preventive migraine treatment is used to reduce frequency, severity and duration of attacks and therefore lightens the burden on the patients' quality of life and reduces disability. Topiramate is one of the preventive migraine treatments of proven efficacy. The mechanism of action underlying the preventive effect of topiramate in migraine remains largely unknown. Using functional magnetic resonance imaging (fMRI) we examined the central effects of a single dose of topiramate (100mg) on trigeminal pain in humans, compared to placebo (mannitol). In this prospective, within subject, randomized, placebo-controlled and double-blind study, 23 healthy participants received a standardized nociceptive trigeminal stimulation and control stimuli whilst being in the scanner. No differences in the subjective intensity ratings of the painful stimuli were observed between topiramate and placebo sessions. In contrast, topiramate significantly decreased the activity in the thalamus and other pain processing areas. Additionally, topiramate increased functional coupling between the thalamus and several brain regions such as the bilateral precuneus, posterior cingulate cortex and secondary somatosensory cortex. These data suggest that topiramate exhibits modulating effects on nociceptive processing in thalamo-cortical networks during trigeminal pain and that the preventive effect of topiramate on frequent migraine is probably mediated by an effect on thalamo-cortical networks. PMID- 28991916 TI - The essential role of optical flow in the peripheral visual field for stable quiet standing: Evidence from the use of a head-mounted display. AB - It has long been thought that vision is the most essential factor in maintaining stable quiet standing compared to other sources (i.e., vestibular and somatosensory inputs) of information. Specifically, several vision studies on postural control have shown evidence for the importance of the visual system, particularly peripheral vision rather than central vision, and optical flow. Nevertheless, to date, no study has manipulated both visual field and optical flow concurrently. In the present study, we experimentally manipulated both the visual field (the central and peripheral visual fields) and the occurrence of optical flow during quiet standing, examining the effects of the visual field and optical flow on postural sway measured in terms of the center of pressure (CoP). Stationary random dot stimuli were presented exclusively in either the central or peripheral visual field, while the occurrence of optical flow was manipulated using a desktop (DTD) or a head-mounted (HMD) display. The optical flow that occurred while using the DTD was a function of the postural sway during quiet standing, while for the HMD, no optical flow occurred even when the body/head swayed during quiet standing. Our results show that the extent of postural sway (e.g., CoP area) was smaller when visual stimuli were presented in the peripheral visual field than that in the central visual field; this was the case while using the DTD alone, with no effects of the peripheral vision on the extent of postural sway while using the HMD. It is therefore suggested that the optical flow occurring in the peripheral visual field is essential for stable quiet standing. PMID- 28991917 TI - Characterization of the catalytic center of the Ebola virus L polymerase. AB - BACKGROUND: Ebola virus (EBOV) causes a severe hemorrhagic fever in humans and non-human primates. While no licensed therapeutics are available, recently there has been tremendous progress in developing antivirals. Targeting the ribonucleoprotein complex (RNP) proteins, which facilitate genome replication and transcription, and particularly the polymerase L, is a promising antiviral approach since these processes are essential for the virus life cycle. However, until now little is known about L in terms of its structure and function, and in particular the catalytic center of the RNA-dependent RNA polymerase (RdRp) of L, which is one of the most promising molecular targets, has never been experimentally characterized. METHODOLOGY/PRINCIPAL FINDINGS: Using multiple sequence alignments with other negative sense single-stranded RNA viruses we identified the putative catalytic center of the EBOV RdRp. An L protein with mutations in this center was then generated and characterized using various life cycle modelling systems. These systems are based on minigenomes, i.e. miniature versions of the viral genome, in which the viral genes are exchanged against a reporter gene. When such minigenomes are coexpressed with RNP proteins in mammalian cells, the RNP proteins recognize them as authentic templates for replication and transcription, resulting in reporter activity reflecting these processes. Replication-competent minigenome systems indicated that our L catalytic domain mutant was impaired in genome replication and/or transcription, and by using replication-deficient minigenome systems, as well as a novel RT-qPCR based genome replication assay, we showed that it indeed no longer supported either of these processes. However, it still showed similar expression to wild type L, and retained its ability to be incorporated into inclusion bodies, which are the sites of EBOV genome replication. CONCLUSIONS/SIGNIFICANCE: We have experimentally defined the catalytic center of the EBOV RdRp, and thus a promising antiviral target regulating an essential aspect of the EBOV life cycle. PMID- 28991919 TI - Optimal coordinated voltage control in active distribution networks using backtracking search algorithm. AB - The growing interest in distributed generation (DG) in recent years has led to a number of generators connected to a distribution system. The integration of DGs in a distribution system has resulted in a network known as active distribution network due to the existence of bidirectional power flow in the system. Voltage rise issue is one of the predominantly important technical issues to be addressed when DGs exist in an active distribution network. This paper presents the application of the backtracking search algorithm (BSA), which is relatively new optimisation technique to determine the optimal settings of coordinated voltage control in a distribution system. The coordinated voltage control considers power factor, on-load tap-changer and generation curtailment control to manage voltage rise issue. A multi-objective function is formulated to minimise total losses and voltage deviation in a distribution system. The proposed BSA is compared with that of particle swarm optimisation (PSO) so as to evaluate its effectiveness in determining the optimal settings of power factor, tap-changer and percentage active power generation to be curtailed. The load flow algorithm from MATPOWER is integrated in the MATLAB environment to solve the multi-objective optimisation problem. Both the BSA and PSO optimisation techniques have been tested on a radial 13-bus distribution system and the results show that the BSA performs better than PSO by providing better fitness value and convergence rate. PMID- 28991918 TI - Rapid enteric testing to permit targeted antimicrobial therapy, with and without Lactobacillus reuteri probiotics, for paediatric acute diarrhoeal disease in Botswana: A pilot, randomized, factorial, controlled trial. AB - INTRODUCTION: Diarrhoeal disease is the second-leading cause of death in young children. Current guidelines recommend treating children with acute non-bloody diarrhea with oral rehydration solutions and zinc, but not antimicrobials. However, in many resource-limited settings, infections with treatable enteric bacterial and protozoan pathogens are common. Probiotics have shown promise as an adjunct treatment for diarrhoea but have not been studied in sub-Saharan Africa. METHODS: We conducted a pilot, factorial, randomized, placebo-controlled trial of children aged 2-60 months hospitalized in Botswana for acute non-bloody diarrhoea. A rapid test-and-treat intervention, consisting of multiplex PCR testing of rectal swabs taken at enrolment, accompanied by targeted antimicrobial therapy if treatable pathogens were detected, was compared to the reference standard of no stool testing. Additionally, Lactobacillus reuteri DSM 17938 x 60 days was compared to placebo treatment. The main objective of this pilot study was to assess feasibility. The primary clinical outcome was the increase in age standardized height (HAZ) at 60 days adjusted for baseline HAZ. RESULTS: Seventy six patients were enrolled over a seven-month study period. We judged that the recruitment rate, lab processing times, communication protocols, provision of specific antimicrobials, and follow-up rates were acceptable. Compared to the reference arm (no stool testing and placebo treatment), the combination of the rapid test-and-treat strategy plus L. reuteri DSM 17938 was associated with an increase of 0.61 HAZ (95% CI 0.09-1.13) and 93% lower odds of recurrent diarrhoea (OR 0.07, 95%CI 0.01-0.61) at 60 days. DISCUSSION: We demonstrated that it was feasible to evaluate the study interventions in Botswana. Despite the small sample size, we observed a statistically significant increase in HAZ at 60 days and significantly lower odds of recurrent diarrhoea in children receiving both rapid test-and-treat and L. reuteri. There is sufficient evidence to warrant proceeding with a larger follow-up trial in a similar setting. PMID- 28991920 TI - Health-related impact on quality of life and coping strategies for chikungunya: A qualitative study in Curacao. AB - INTRODUCTION: Chikungunya is an emerging public health problem in tropical and subtropical regions, due to ongoing transmission and its incapacitating acute disease phase, and chronic sequelae. The disease is responsible for a major impact on Health Related Quality of Life (HRQoL), which may last several years. To our knowledge, this study is the first qualitative examination of HRQoL and coping strategies of chikungunya-infected individuals. METHODS: Qualitative research methods consisted of 20 in-depth interviews and seven Focus Group Discussions (FGDs), n = 50. Analysis was based on the principles of the grounded theory. RESULTS: Different impacts on HRQoL were reported. The physical and emotional domains of the HRQoL were mainly affected by chikungunya, while social and individual financial consequences were limited. Individual financial impact was limited through the universal health care program of Curacao. Long-term lingering musculoskeletal and other manifestations caused significant pain and limited mobility. Hence, participants experienced dependency, impairment of normal daily life activities, moodiness, hopelessness, a change of identity, and insecurity about their future. The unpredictable nature and consequences of chikungunya gave rise to various coping strategies. Problem-focused coping styles led to higher uptake of medical care and were linked to more negative impact of HRQoL, whereas emotional coping strategies focusing on acceptance of the situation were linked to less uptake of medical care and more positive impact on HRQoL. CONCLUSIONS: This study provides an in-depth understanding of acute and long-term HRQoL impact of chikungunya. The results can better inform health promotion policies and interventions. Messages to the public should focus on promoting healthy and efficient coping strategies, in order to prevent additional stress in affected individuals. PMID- 28991921 TI - The impact of nutritional supplement intake on diet behavior and obesity outcomes. AB - After decades-old efforts to nudge consumers towards healthier lifestyles through dietary guidelines, diet-related diseases are on the rise. In addition, a growing share of U.S. consumers proactively chooses nutritional supplements as an alternative preventative way of maintaining good health, a $25.5 billion industry in the United States. This paper investigates possible linkages between the economics of consumer supplement choices and the relationship to important dietary and health outcomes. We use National Health and Nutrition Examination Survey (NHANES) data to estimate the impact of nutritional supplements intake on respondent's body weight outcomes, controlling for diet quality.: The focus of this article is to determine whether nutritional supplements takers differ from non-takers with regard to their health outcomes when controlling for differences in diet quality, based on individual Healthy Eating Index (HEI-2010) score. The analysis applies treatment effects estimators that account for the selection bias and endogeneity of self-reported behavior and diet-health outcomes. The analysis demonstrates a negative association between supplement intake and BMI but no significant effect on an individual's diet quality. Our findings suggest that individuals proactively invest into their health by taking nutritional supplements instead of improving diet quality through more nutritious food choices. Our results provide important contributions to the literature on a key food policy issue. Knowledge of the determinants of supplement demand in the context of strong diet-health trends should also be helpful to stakeholders in the U.S. produce sector in their competition over consumer market share. PMID- 28991922 TI - Clonal dominance and transplantation dynamics in hematopoietic stem cell compartments. AB - Hematopoietic stem cells in mammals are known to reside mostly in the bone marrow, but also transitively passage in small numbers in the blood. Experimental findings have suggested that they exist in a dynamic equilibrium, continuously migrating between these two compartments. Here we construct an individual-based mathematical model of this process, which is parametrised using existing empirical findings from mice. This approach allows us to quantify the amount of migration between the bone marrow niches and the peripheral blood. We use this model to investigate clonal hematopoiesis, which is a significant risk factor for hematologic cancers. We also analyse the engraftment of donor stem cells into non conditioned and conditioned hosts, quantifying the impact of different treatment scenarios. The simplicity of the model permits a thorough mathematical analysis, providing deeper insights into the dynamics of both the model and of the real world system. We predict the time taken for mutant clones to expand within a host, as well as chimerism levels that can be expected following transplantation therapy, and the probability that a preconditioned host is reconstituted by donor cells. PMID- 28991923 TI - Relations between mental health team characteristics and work role performance. AB - Effective mental health care requires a high performing, interprofessional team. Among 79 mental health teams in Quebec (Canada), this exploratory study aims to 1) determine the association between work role performance and a wide range of variables related to team effectiveness according to the literature, and to 2) using structural equation modelling, assess the covariance between each of these variables as well as the correlation with other exogenous variables. Work role performance was measured with an adapted version of a work role questionnaire. Various independent variables including team manager characteristics, user characteristics, team profiles, clinical activities, organizational culture, network integration strategies and frequency/satisfaction of interactions with other teams or services were analyzed under the structural equation model. The later provided a good fit with the data. Frequent use of standardized procedures and evaluation tools (e.g. screening and assessment tools for mental health disorders) and team manager seniority exerted the most direct effect on work role performance. While network integration strategies had little effect on work role performance, there was a high covariance between this variable and those directly affecting work role performance among mental health teams. The results suggest that the mental healthcare system should apply standardized procedures and evaluation tools and, to a lesser extent, clinical approaches to improve work role performance in mental health teams. Overall, a more systematic implementation of network integration strategies may contribute to improved work role performance in mental health care. PMID- 28991924 TI - Application of a loop-mediated isothermal amplification (LAMP) assay targeting cox1 gene for the detection of Clonorchis sinensis in human fecal samples. AB - BACKGROUND: Clonorchiasis is prevalent in the Far East, and a major health problem in endemic areas. Infected persons may experience, if not treated, serious complications such as bile stone formation, pyogenic cholangitis, and even cholangiocarcinoma. Early diagnosis and treatment are important to prevent serious complications and, therefore, the simple and reliable diagnostic method is necessary to control clonorchiasis in endemic areas, where resources for the diagnosis are limited. METHODOLOGY/PRINCIPLE FINDINGS: The loop-mediated isothermal amplification (LAMP) assay has been applied for the detection of Clonorchis sinensis DNA. Six primers targeting eight locations on the cytochrome c oxidase subunit 1 gene of C. sinensis were designed for species-specific amplification using the LAMP assay. The LAMP assay was sensitive enough to detect as little as 100 fg of C. sinensis genomic DNA and the detection limit in 100 mg of stool was as low as one egg. The assay was highly specific because no cross reactivity was observed with the DNA of other helminths, protozoa or Escherichia coli. Then, LAMP assay was applied to human fecal samples collected from an endemic area of clonorchiasis in Korea. Using samples showing consistent results by both Kato-Katz method and real-time PCR as reference standards, the LAMP assay showed 97.1% (95% CI, 90.1-99.2) of sensitivity and 100% (95% CI, 92.9-100) of specificity. In stool samples with more than 100 eggs per gram of feces, the sensitivity achieved 100%. CONCLUSIONS: To detect C. sinensis in human fecal samples, the LAMP assay was applied and achieved high sensitivity and specificity. The LAMP assay can be utilized in field laboratories as a powerful tool for diagnosis and epidemiological survey of clonorchiasis. PMID- 28991926 TI - Image-based model of the spectrin cytoskeleton for red blood cell simulation. AB - We simulate deformable red blood cells in the microcirculation using the immersed boundary method with a cytoskeletal model that incorporates structural details revealed by tomographic images. The elasticity of red blood cells is known to be supplied by both their lipid bilayer membranes, which resist bending and local changes in area, and their cytoskeletons, which resist in-plane shear. The cytoskeleton consists of spectrin tetramers that are tethered to the lipid bilayer by ankyrin and by actin-based junctional complexes. We model the cytoskeleton as a random geometric graph, with nodes corresponding to junctional complexes and with edges corresponding to spectrin tetramers such that the edge lengths are given by the end-to-end distances between nodes. The statistical properties of this graph are based on distributions gathered from three dimensional tomographic images of the cytoskeleton by a segmentation algorithm. We show that the elastic response of our model cytoskeleton, in which the spectrin polymers are treated as entropic springs, is in good agreement with the experimentally measured shear modulus. By simulating red blood cells in flow with the immersed boundary method, we compare this discrete cytoskeletal model to an existing continuum model and predict the extent to which dynamic spectrin network connectivity can protect against failure in the case of a red cell subjected to an applied strain. The methods presented here could form the basis of disease- and patient-specific computational studies of hereditary diseases affecting the red cell cytoskeleton. PMID- 28991925 TI - Next-generation ELISA diagnostic assay for Chagas Disease based on the combination of short peptidic epitopes. AB - Chagas Disease, caused by the protozoan Trypanosoma cruzi, is a major health and economic problem in Latin America for which no vaccine or appropriate drugs for large-scale public health interventions are yet available. Accurate diagnosis is essential for the early identification and follow up of vector-borne cases and to prevent transmission of the disease by way of blood transfusions and organ transplantation. Diagnosis is routinely performed using serological methods, some of which require the production of parasite lysates, parasite antigenic fractions or purified recombinant antigens. Although available serological tests give satisfactory results, the production of reliable reagents remains laborious and expensive. Short peptides spanning linear B-cell epitopes have proven ideal serodiagnostic reagents in a wide range of diseases. Recently, we have conducted a large-scale screening of T. cruzi linear B-cell epitopes using high-density peptide chips, leading to the identification of several hundred novel sequence signatures associated to chronic Chagas Disease. Here, we performed a serological assessment of 27 selected epitopes and of their use in a novel multipeptide-based diagnostic method. A combination of 7 of these peptides were finally evaluated in ELISA format against a panel of 199 sera samples (Chagas-positive and negative, including sera from Leishmaniasis-positive subjects). The multipeptide formulation displayed a high diagnostic performance, with a sensitivity of 96.3% and a specificity of 99.15%. Therefore, the use of synthetic peptides as diagnostic tools are an attractive alternative in Chagas' disease diagnosis. PMID- 28991927 TI - Current status of indwelling urinary catheter utilization and catheter-associated urinary tract infection throughout hospital wards in Korea: A multicenter prospective observational study. AB - To evaluate the frequency and appropriateness of indwelling urinary catheters (IUC) use and the incidence of catheter-associated urinary tract infections (CA UTI), and explore the risk factors for CA-UTI in hospitals as a whole, we conducted a study. This study was divided into two parts; a point-prevalence study on Dec 12th 2012 and a prospective cohort study from Dec 13th 2012 to Jan 9th 2013 were performed in six hospitals in Korea. All hospitalized patients with newly-placed IUCs were enrolled and monitored weekly for 28 days after IUC placement. In the point-prevalence study, the IUCs were present in median 14.9/100 hospitalized patients (1Q 14, 3Q 16) across the six hospitals. In the prospective cohort study, the median IUC-days per patient was 5 (1Q 3, 3Q 10) and the median CA-UTI prevalence per 1,000 catheter days was 1.9 (1Q 0.7, 3Q 3.8) with significant inter-hospital variation. The proportion of patients with inappropriate IUC maintenance increased with number of IUC-days (8.5% on day 7, 9.4% on day 14, 16.3% on day 21, and 23.1% on day 28). Urinary output monitoring (23/36, 63.9%) was the most common indication for inappropriate use after 1 week of ICU placement. In multivariate analysis, IUC-days was significantly associated with the development of CA-UTI (odds ratio 1.122, 95% confidence interval 1.074 1.173, P< 0.001). IUC-days and CA-UTI rates vary between hospitals. IUC-days is a risk factor for CA-UTI, and is correlated with inappropriate use. PMID- 28991928 TI - Clinical significance of pretreatment serum levels of VEGF and its receptors, IL- 8, and their prognostic value in type I and II endometrial cancer patients. AB - OBJECTIVES: The study aimed to assess the usefulness of the determination of cytokines: IL-8, VEGF and its soluble receptors: VEGF-R1, VEGF-R2 in patients with endometrial cancer (EC). MATERIAL/METHODS: The study group consisted of 118 patients with EC subjected to surgical treatment. Before the treatment we determined the serum levels of cytokines IL-8, and VEGF as well as VEGFR1 and VEGFR2 receptors. For comparison, the concentration of CA 125 was also measured. VEGFR1 and CA 125 were determined in the COBAS e601 system using Roche Diagnostics kits, while IL-8, VEGF and VEGFR2 were measured by ELISA assay using R&D Systems kits. RESULTS: The concentrations of IL-8, VEGF, VEGFR1 and CA 125 allowed to distinguish patients for the control group. The highest diagnostic sensitivity has been shown for the concentrations of VEGF (AUC = 0.904) and IL-8 (AUC = 0.818). Among all studied parameters only CA125 concentrations increased with the clinical stage; being significantly higher in patients in FIGO III-IV, than FIGO I-IB. In patients at the FIGO stage I-IB, complementary determinations of CA 125 and VEGF resulted in the largest increase of diagnostic sensitivity. Patients with metastases to the para-aortic lymph nodes had significantly higher levels of VEGF compared to subjects without such lesions. The concentrations of IL-8 were an independent prognostic factor in the assessment of overall survival in patients with type I endometrial cancer, while the concentrations of VEGFR2 in those with type II. CONCLUSIONS: In patients with endometrial cancer, the clinical usefulness of IL-8 and VEGFR2 measurements as the potential prognostic factors has been demonstrated. In type I, the concentrations of IL-8 determined before treatment can be helpful in predicting overall survival. In patients qualified to type II EC, the concentrations of VEGFR2 have the value of an independent prognostic factor for overall survival, this requires research on larger groups of patients. The increased levels of VEGF may be useful in the preoperative assessment of the status of para-aortic lymph nodes. PMID- 28991929 TI - Addressing Unmet Needs With Injectable Medications in Type 2 Diabetes Treatment: Medications for Type 2 Diabetes Mellitus: A Work in Progress. AB - Many factors contribute to poor adherence to medications. Some involve the patient, others the health care provider, while others concern limitations with the medications themselves. PMID- 28991930 TI - Addressing Unmet Needs With Injectable Medications in Type 2 Diabetes Treatment: Role of Injectable Medications in Type 2 Diabetes Treatment. AB - This article describes the roles of injectable glucose-lowering medications, specifically basal insulin and GLP-1RAs, as recommended in current guidelines and the evidence supporting these recommendations. PMID- 28991931 TI - Addressing Unmet Needs With Injectable Medications in Type 2 Diabetes Treatment: Basal insulins. AB - In healthy humans, the timing and amount of insulin release are exquisitely tied to the body's metabolic demands. Insulin is released at a relatively constant rate over 24 hours to meet the body's basal metabolic needs. In addition, insulin is released in short bursts in response to nutrient intake, as well as in response to changes in peripheral utilization, sensitivity, and endogenous production.To approximate this physiologic state, 2 general types of insulin formulations have been developed. Basal insulins are intended to address the body's basal metabolic needs over 24 hours, and prandial (or bolus) insulins to address the rapid rise in blood glucose in the postprandial state. The quest for a basal insulin with a constant physiologic effect over 24 hours has been challenging, in part because the subcutaneous route of administration remains the most practical, yet physiologically unnatural route for administering insulin. PMID- 28991932 TI - Addressing Unmet Needs With Injectable Medications in Type 2 Diabetes Treatment: Glucagon-Like Peptide-1 Receptor Agonists. AB - Since 2005, four new GLP-1RAs (liraglutide, albiglutide, dulaglutide, and lixisenatide) and a once-weekly formulation of exenatide were approved for the treatment of persons with T2DM. Another GLP-1RA, semaglutide, is under review by the FDA, as is exenatide administered via an osmotic mini-pump. PMID- 28991933 TI - Addressing Unmet Needs With Injectable Medications in Type 2 Diabetes Treatment: Using Combinations of a Basal Insulin and a Glucagon-Like Peptide-1 Receptor Agonist. AB - This article presents the rationale and data for combining a basal insulin with a GLP-1RA, including as fixed-ratio products. PMID- 28991934 TI - Is obesity a disease? PMID- 28991936 TI - 8 viral exanthems of childhood. AB - Some share features, making them difficult to distinguish. Others may not be on your radar. Here we review 8 you're likely to see or need to exclude. PMID- 28991935 TI - Obesity: When to consider medication. AB - These 4 cases illustrate how weight loss drugs--including the 4 newest--can be integrated into a treatment plan that includes diet, exercise, and behavior modification. PMID- 28991937 TI - Effectively engaging patients in everyday health-care decisions. AB - You can improve health outcomes and patient satisfaction--without increasing the length of the patient visit--by employing the tenets of shared decision-making. PMID- 28991938 TI - Intraoral lesion . history of cirrhosis and smoking . Dx? AB - A 56-year-old white man presented at our dental clinic for routine care. The intraoral examination revealed an asymptomatic red lesion with white vesicle-like areas on the right side of the soft palate. The extraoral examination was normal, and regional lymph nodes were nonpalpable. The patient's medical history included liver cirrhosis and pancreatitis. He also had a 30-year history of alcohol misuse (1-5 drinks per day) and a 30-pack-year smoking history. (The patient had stopped drinking at the time of presentation, and had quit smoking 2 years earlier.) We instructed him to gargle with warm salt water at home and return in 2 weeks. At follow-up, the lesion was unresolved, so a biopsy was performed. PMID- 28991939 TI - PURLs: When to "CAP" off treatment for pneumonia. AB - Prescribe 5 days of antibiotic treatment for inpatients with community-acquired pneumonia because it produces the same clinical success rates as longer treatment regimens, but is associated with fewer negative patient outcomes. PMID- 28991940 TI - Posttraumatic stress disorder: Often missed in primary care. AB - DeSean W, a 47-year-old man, returned to his primary care clinic with a new complaint of epigastric burning that had been bothering him for the past 4 months. He had tried several over-the-counter remedies, which provided no relief. He also remained concerned--despite assurances to the contrary at previous clinic visits--that he had contracted a sexually-transmitted disease (STD) after going to a bar one night 4 to 5 months ago. At 2 other clinic visits since that time, STD test results were negative. At this current visit, symptoms and details of sexual history were unchanged since the last visit, with the exception of the epigastric pain. When asked if he thought he had contracted an STD through a sexual encounter the night he went to the bar, he emphatically said he would not cheat on his wife. Surprisingly, given his concern, he avoided further discussion on modes of contracting an STD. The physician prescribed ranitidine 150 mg bid for the epigastric burning and explained, once more, the significance of the STD test results. However, he also decided to further examine Mr. W's concern about STDs and the night he may have contracted one. HOW WOULD YOU PROCEED WITH THIS PATIENT? PMID- 28991941 TI - Fever, rash, and leukopenia in a 32-year-old man . Dx? AB - A 32-year-old man was admitted to our hospital with fever, chills, malaise, leukopenia, and a rash. About 3 weeks earlier, he'd had oral maxillofacial surgery and started a 10-day course of prophylactic amoxicillin/clavulanic acid. Fifteen days after the surgery, he developed a fever (temperature, 103 degrees F), chills, arthralgia, myalgia, cough, diarrhea, and malaise. He was seen by his physician, who obtained a chest x-ray showing a lingular infiltrate. The physician diagnosed influenza and pneumonia in this patient, and prescribed oseltamivir, azithromycin, and an additional course of amoxicillin/clavulanic acid. Upon admission to the hospital, laboratory tests revealed a white blood cell count (WBC) of 3.1 k/mcL (normal: 3.2-10.8 k/mcL). The patient's physical examination was notable for lip edema, white mucous membrane plaques, submandibular and inguinal lymphadenopathy, and a morbilliform rash across his chest. Broad-spectrum antibiotics were initiated for presumed sepsis. On hospital day (HD) 1, tests revealed a WBC count of 1.8 k/mcL, an erythrocyte sedimentation rate of 53 mm/hr (normal: 20-30 mm/hr for women, 15-20 mm/hr for men), and a C reactive protein level of 6.7 mg/dL (normal: <0.5 mg/dL). A repeat chest x-ray and orofacial computerized tomography scan were normal. By HD 3, all bacterial cultures were negative, but the patient was positive for human herpesvirus-6 on viral cultures. His leukopenia persisted and he had elevated levels of alanine transaminase ranging from 40 to 73 U/L (normal: 6-43 U/L) and aspartate aminotransferase ranging from 66 to 108 U/L (normal range: 10-40 U/L), both downtrending during his hospitalization. He also had elevated levels of antinuclear antibodies and anti-Smith antibody titers. A posterior-auricular biopsy was consistent with lymphocytic perivasculitis. The rash continued to progress, involving his chest, abdomen, and face. Bacterial and viral cultures remained negative and on HD 4, broad-spectrum antibiotics were discontinued. PMID- 28991942 TI - Confusion recurs 2 weeks after fall. AB - A 77-year-old woman presented to the emergency department complaining of a headache following a syncopal episode (while standing) earlier that day. She said that she'd lost consciousness for several minutes, and then experienced several minutes of mild confusion that resolved spontaneously. On physical exam, she was oriented to person and place, but not time. She had a contusion in her left occipitoparietal region without extensive bruising or deformity. The patient had normal cardiopulmonary, abdominal, and neurologic exams. Her past medical history included hypertension and normal pressure hydrocephalus, and her vital signs were within normal limits. She was taking aspirin once daily. The patient's initial head and neck computerized tomography (CT) scans were normal, but she was hospitalized because of her confusion. During her hospitalization, the patient had mild episodic headaches that resolved with acetaminophen. The next day, her confusion resolved, and repeat CT scans were unchanged. She was discharged within 24 hours. Two weeks later, the patient returned to the hospital after her daughter found her on the toilet, unable to stand up from the sitting position. She was confused and experienced a worsening of headache during transport to the hospital. No recurrent falls or additional episodes of trauma were reported. A CT scan was performed. WHAT IS YOUR DIAGNOSIS? HOW WOULD YOU TREAT THIS PATIENT? PMID- 28991943 TI - Are oral emergency contraceptives a safe and effective form of long-term birth control? AB - Yes, but not as effective as some other methods. Annual pregnancy rates in women using pericoital levonorgestrel 150 mcg to 1 mg range from 4.9% to 8.9%; menstrual irregularity is the most common adverse effect (strength of recommendation [SOR]: B, Cochrane review of lower-quality trials). In women younger than 35 years who have sexual intercourse 6 or fewer times per month, correct and consistent use of pericoital levonorgestrel 1.5 mg results in an annual pregnancy rate of 11% (SOR: B, one large prospective, open-label trial). Pericoital contraception is less effective than long-acting reversible contraceptives (annual pregnancy rates of 0.05%-0.8%) or perfect use of combined oral contraceptives (0.3% annual pregnancy rate), but similar to, or better than, typical use of combined oral contraception (9%) and condoms (18%). PMID- 28991944 TI - Sound and Light Levels Are Similarly Disruptive in ICU and non-ICU Wards. AB - OBJECTIVE: To compare ambient sound and light levels, including SLCs, in ICU and non-ICU environments. DESIGN: Observational study. SETTING: Tertiary-care hospital. MEASUREMENTS: Sound measurements of 0.5 Hz were analyzed to provide average hourly sound levels, sound peaks, and SLCs =17.5 decibels (dB). For light data, measurements taken at 2-minute intervals provided average and maximum light levels. RESULTS: The ICU rooms were louder than non-ICU wards; hourly averages ranged from 56.1 +/- 1.3 dB to 60.3 +/- 1.7 dB in the ICU, 47.3 +/- 3.7 dB to 55.1 +/- 3.7 dB on the telemetry floor, and 44.6 +/- 2.1 dB to 53.7 +/- 3.6 dB on the general ward. However, SLCs = 17.5 dB were not statistically different (ICU, 203.9 +/- 28.8 times; non-ICU, 270.9 +/- 39.5; P = 0.11). In both ICU and non-ICU wards, average daytime light levels were <250 lux, and peak light levels occurred in the afternoon and early evening. CONCLUSIONS: Quieter, non-ICU wards have as many SLCs as ICUs do, which has implications for quality improvement measurements. Efforts to further reduce average noise levels might be counterproductive. Light levels in the hospital (ICU and non-ICU) may not be optimal for maintenance of a normal circadian rhythm for most people. PMID- 28991945 TI - Associations of Physician Empathy with Patient Anxiety and Ratings of Communication in Hospital Admission Encounters. AB - OBJECTIVE: To assess the association between the frequency of empathic physician responses with patient anxiety, ratings of communication, and encounter length during hospital admission encounters. DESIGN: Analysis of coded audio-recorded hospital admission encounters and pre- and postencounter patient survey data. SETTING: Two academic hospitals. PATIENTS: Seventy-six patients admitted by 27 attending hospitalist physicians. MEASUREMENTS: Recordings were transcribed and analyzed by trained coders, who counted the number of empathic, neutral, and nonempathic verbal responses by hospitalists to their patients' expressions of negative emotion. We developed multivariable linear regression models to test the association between the number of these responses and the change in patients' State Anxiety Scale (STAI-S) score pre- and postencounter and encounter length. We used Poisson regression models to examine the association between empathic response frequency and patient ratings of the encounter. RESULTS: Each additional empathic response from a physician was associated with a 1.65-point decline in the STAI-S anxiety scale (95% confidence interval [CI], 0.48-2.82). Frequency of empathic responses was associated with improved patient ratings for covering points of interest, feeling listened to and cared about, and trusting the doctor. The number of empathic responses was not associated with encounter length (percent change in encounter length per response 1%; 95% CI, -8%-10%). CONCLUSIONS: Responding empathically when patients express negative emotion was associated with less patient anxiety and higher ratings of communication but not longer encounter length. PMID- 28991946 TI - A Concise Tool for Measuring Care Coordination from the Provider's Perspective in the Hospital Setting. AB - BACKGROUND: To support hospital efforts to improve coordination of care, a tool is needed to evaluate care coordination from the perspective of inpatient healthcare professionals. OBJECTIVES: To develop a concise tool for assessing care coordination in hospital units from the perspective of healthcare professionals, and to assess the performance of the tool in measuring dimensions of care coordination in 2 hospitals after implementation of a care coordination initiative. METHODS: We developed a survey consisting of 12 specific items and 1 global item to measure provider perceptions of care coordination across a variety of domains, including teamwork and communication, handoffs, transitions, and patient engagement. The questionnaire was distributed online between October 2015 and January 2016 to nurses, physicians, social workers, case managers, and other professionals in 2 tertiary care hospitals. RESULTS: A total of 841 inpatient care professionals completed the survey (response rate = 56.6%). Among respondents, 590 (75%) were nurses and 37 (4.7%) were physicians. Exploratory factor analysis revealed 4 subscales: (1) Teamwork, (2) Patient Engagement, (3) Handoffs, and (4) Transitions (Cronbach's alpha 0.84-0.90). Scores were fairly consistent for 3 subscales but were lower for patient engagement. There were minor differences in scores by profession, department, and hospital. CONCLUSIONS: The new tool measures 4 important aspects of inpatient care coordination with evidence for internal consistency and construct validity, indicating that the tool can be used in monitoring, evaluating, and planning care coordination activities in hospital settings. PMID- 28991947 TI - Regional Variation in Standardized Costs of Care at Children's Hospitals. AB - OBJECTIVE: (1) To evaluate regional variation in costs of care for 3 inpatient pediatric conditions, (2) assess potential drivers of variation, and (3) estimate cost savings from reducing variation. DESIGN/SETTING: Retrospective cohort study of hospitalizations for asthma, diabetic ketoacidosis (DKA), and acute gastroenteritis (AGE) at 46 children 35) comprised the high psychiatric comorbidity group. Patients with 1 to 2 positive screens were labeled the low to moderate (low-moderate) psychiatric comorbidity group. Patients with 3 negative screens were labeled the no psychiatric morbidity group. Thirty-one percent of patients met the criteria for high psychiatric comorbidity. After adjusting for age, gender, Charlson Comorbidity Index, discharge status, and prior history of depression and anxiety, patients who had high psychiatric comorbidity were more likely to have a poorer QoL compared with the low-moderate comorbidity and no morbidity groups, as measured by a lower EuroQol 5 dimensions questionnaire 3 level Index (no, 0.69 +/- 0.25; low-moderate, 0.70 +/- 0.19; high, 0.48 +/- 0.24; P = 0.017). Future studies should confirm these findings and examine whether survivors of ICU delirium with high psychiatric comorbidity have different treatment needs from survivors with lower psychiatric comorbidity. PMID- 28991953 TI - Dust in the Wind. PMID- 28991954 TI - Tools, Clinical Prediction Rules, and Algorithms for the Insertion of Peripheral Intravenous Catheters in Adult Hospitalized Patients: A Systematic Scoping Review of Literature. AB - BACKGROUND: First-time peripheral intravenous catheter (PIVC) insertion success is dependent on patient, clinician, and product factors. Failed PIVC insertion are an under-recognized clinical phenomenon. OBJECTIVE: To provide a scoping review of decision aids for PIVC insertion including tools, clinical prediction rules, and algorithms (TRAs) and their findings on factors associated with insertion success. METHODS: In June 2016, a systematic literature search was performed using the medical subject heading of peripheral catheterization and tool* or rule* or algorithm*. Data extraction included clinician, patient, and/or product variables associated with PIVC insertion success. Information about TRA reliability, validity, responsiveness, and utility was also extracted. RESULTS: We screened 36 studies, and included 13 for review. Seven papers reported insertion success ranging from 61%-90% (4030 insertion attempts), 6 on validity, and 5 on reliability, with none reporting on responsiveness and utility. Failed insertions were associated with obesity (odds ratio [OR], 0.71-1.7; 2 studies) and smaller gauge PIVCs (OR, 6.4; 95% Confidence Interval [CI}, 3.4-11.9). Successful inser tions were associated with visible veins (OR, 0.87-3.63; 3 studies) or palpable veins (OR, 0.79-5.05; 3 studies) and inserters with greater procedural volume (OR, 4.4; 95% CI, 1.6-12.1) or who predicted that insertion would be successful (OR, 1.06; 95% CI, 1.04-1.07). Definitions of insertion difficulty are heterogeneous such as time to insert to a number of failed attempts. CONCLUSIONS: Few well-validated reliable TRAs exist for PIVC insertion. Patients would benefit from a validated, clinically pragmatic TRA that matches insertion difficulty with clinician competency. PMID- 28991955 TI - A Search for Tools to Support Decision-Making for PIVC Use. PMID- 28991956 TI - Noise and Light Pollution in the Hospital: A Call for Action. PMID- 28991957 TI - Planned, Related or Preventable: Defining Readmissions to Capture Quality of Care. PMID- 28991958 TI - From supramolecular polymers to multi-component biomaterials. AB - The most striking and general property of the biological fibrous architectures in the extracellular matrix (ECM) is the strong and directional interaction between biologically active protein subunits. These fibers display rich dynamic behavior without losing their architectural integrity. The complexity of the ECM taking care of many essential properties has inspired synthetic chemists to mimic these properties in artificial one-dimensional fibrous structures with the aim to arrive at multi-component biomaterials. Due to the dynamic character required for interaction with natural tissue, supramolecular biomaterials are promising candidates for regenerative medicine. Depending on the application area, and thereby the design criteria of these multi-component fibrous biomaterials, they are used as elastomeric materials or hydrogel systems. Elastomeric materials are designed to have load bearing properties whereas hydrogels are proposed to support in vitro cell culture. Although the chemical structures and systems designed and studied today are rather simple compared to the complexity of the ECM, the first examples of these functional supramolecular biomaterials reaching the clinic have been reported. The basic concept of many of these supramolecular biomaterials is based on their ability to adapt to cell behavior as a result of dynamic non-covalent interactions. In this review, we show the translation of one dimensional supramolecular polymers into multi-component functional biomaterials for regenerative medicine applications. PMID- 28991959 TI - A novel explanation for the increased conductivity in annealed Al-doped ZnO: an insight into migration of aluminum and displacement of zinc. AB - A combined experimental and first-principles study is performed to study the origin of conductivity in ZnO:Al nanoparticles synthesized under controlled conditions via a reflux route using benzylamine as a solvent. The experimental characterization of the samples by Raman, nuclear magnetic resonance (NMR) and conductivity measurements indicates that upon annealing in nitrogen, the Al atoms at interstitial positions migrate to the substitutional positions, creating at the same time Zn interstitials. We provide evidence for the fact that the formed complex of AlZn and Zni corresponds to the origin of the Knight shifted peak (KS) we observe in 27Al NMR. As far as we know, the role of this complex has not been discussed in the literature to date. However, our first-principles calculations show that such a complex is indeed energetically favoured over the isolated Al interstitial positions. In our calculations we also address the charge state of the Al interstitials. Further, Zn interstitials can migrate from AlZn and possibly also form Zn clusters, leading to the observed increased conductivity. PMID- 28991960 TI - Delocalized triplet state in porphyrin J-aggregates revealed by EPR spectroscopy. AB - In this work, the electronic structure of the triplet state of self-assembled J aggregates of tetrakis(4-sulfonatophenyl)porphyrin (TPPS) has been characterized by means of time-resolved electron paramagnetic resonance spectroscopy. Several insights into the triplet properties of the aggregate have been gained through comparison with the corresponding monomeric unit in both free base and acidified forms. Molecular distortions in the monomeric acidified TPPS cause variation in its zero-field splitting parameters and a redirection of triplet spin sublevel activity. The aggregation process does not alter the mechanism of triplet state population compared to the acidified monomer but it is accompanied by a further reduction in the zero-field splitting parameter D, which is possibly indicative of the formation of a delocalized triplet state species. The detection of a long lived spin-polarized radical species also proves polaron generation and movement to a trap site in the J-aggregates. PMID- 28991961 TI - B(OH)4- hydration and association in sodium metaborate solutions by X-ray diffraction and empirical potential structure refinement. AB - X-ray diffraction is used to study the structure of aqueous sodium metaborate solutions at salt concentrations of 1, 3, and 5 (oversaturated) mol dm-3. The X ray structure factors are subjected to empirical potential structure refinement (EPSR) modelling to extract the individual site-site pair correlation functions, the coordination numbers, and the spatial density functions (three-dimensional structure) of ion hydration and association as well as solvent water in the borate solutions. The sodium ion is surrounded on average by (5.4 +/- 0.7), (4.6 +/- 1.0), and (3.7 +/- 1.2) water molecules at 1, 3, and 5 mol dm-3, respectively, with the Na-O (H2O) distance of 2.34 A. The decrease in hydration number of the sodium ion is compensated by direct binding of the oxygen atom of the borate ion, B(OH)4-, with the average coordination number of (0.2 +/- 0.5), (1.0 +/- 0.8), and (2.1 +/- 1.3) at the Na-O(B) distance of 2.34 A to keep the octahedral hydration shell of the sodium ion. The average number of water molecules around the borate ion is (13.9 +/- 1.8), (14.2 +/- 1.8), and (16.1 +/- 2.4) per borate ion with increasing salt concentration with the B-O(H2O) distance of 3.72 A. The number of nearest-neighbour water molecules around a central water molecule in a solvent decreases as (4.8 +/- 1.2), (3.8 +/- 1.1), and (2.8 +/- 1.1) with an increase in salt concentration with the O(H2O)-O(H2O) distance of 2.79 A. The Na+-B(OH)4- ion association is characterized by the Na-O(B) and Na-B pair correlation functions. The Na-B interactions are observed at 3.00 A as a shoulder and 3.57 A as a main peak in the site-site pair correlation function, suggesting two occupancy sites of Na+ with one for the edge-shared bidentate bonding and the other for the corner-shared monodentate bonding. The total number of Na-B interactions at 3.00 and 3.57 A is consistent with that of the Na-O(B) interactions. The detailed three-dimensional structure of the ion hydration and association is visualized as a function of salt concentration. The structure and stability of [NaB(OH)4(H2O)6]0 clusters are further investigated by DFT calculations, and the most likely structure is proposed and cross-checked. PMID- 28991963 TI - Orthogonal enzymatic reactions for rapid crosslinking and dynamic tuning of PEG peptide hydrogels. AB - Stiffening of the extracellular matrix is a hallmark in cancer progression, embryonic development, and wound healing. To mimic this dynamic process, our work explored orthogonal enzymatic reactions capable of modulating the properties of poly(ethylene glycol) (PEG)-peptide hydrogels. A hepta-mutant bacterial transpeptidase sortase A (SrtA7M) was used to ligate two PEG-peptide macromers (i.e., PEG-YLPRTG and NH2-GGGG-PEG) into a primary hydrogel network. The hydrogels were dynamically stiffened using mushroom tyrosinase (MT), which oxidized tyrosine residues into di-tyrosine and led to increased matrix stiffness. After confirming the expression and enhanced catalytic activity of SrtA7M, we investigated the cytocompatibility of the enzymatic reaction with a mouse insulinoma cell line, MIN6. In addition, we altered peptide substrate concentrations and evaluated their influence on primary hydrogel network properties and MT-triggered stiffening. Using a pancreatic cancer cell line, COLO 357, the effect of MT-triggered stiffening on spheroid formation was investigated. We found that cell spheroids formed in hydrogels that were exposed to MT were significantly smaller than spheroids formed without MT incubation, suggesting that matrix stiffening played a crucial role in the sizes of cancer cell spheroids. Through utilizing highly specific and orthogonal enzymatic reactions, this hydrogel platform permits rapid and mild in situ cell encapsulation, as well as dynamic control of matrix stiffness for investigating the role of matrix stiffening on cell fate processes. PMID- 28991964 TI - Visible-light induced di- and trifluoromethylation of N-benzamides with fluorinated sulfones for the synthesis of CF2H/CF3-containing isoquinolinediones. AB - A general visible light induced direct difluoromethylation of N-methacryloyl benzamides by using difluoromethyl sulfone was developed. In addition, photoredox catalyzed trifluoromethylation of N-methacryloyl benzamides with trifluoromethyl sulfone via a similar radical process was also achieved. This method allows for an efficient and practical synthesis of a variety of CF2H/CF3-containing isoquinoline-1,3(2H,4H)-diones in moderate to good yields. The reaction features mild reaction conditions, operational simplicity, and a broad substrate scope. PMID- 28991965 TI - Meta-Analysis of Phosphorus Loss from No-Till Soils. AB - Agriculture is a significant contributor to phosphorus (P) enrichment in aquatic ecosystems. No-till (NT) farming has been proposed as an alternative approach to conventional tillage (CT) in reducing soil P export, but published data have shown contrasting impacts, likely due to the interacting effects of different physical (climate region, rainfall variability, transport pathway, slope gradient) and management variables (NT duration, crop species). We conducted a meta-analysis to understand the extent to which each of these variables controls the concentration and load of different P fractions (dissolved P, particulate P) in agricultural runoff and leaching. In comparison with CT, particulate P loss was significantly lower with NT adoption (45 and 55% reduction in concentration and load, respectively), but an increase in dissolved P loss was observed. The extent of the reduction or increase, however, varied with different physical and management variables. In comparison with CT, for example, NT was not effective in reducing particulate P concentration during wet years and particulate P load on steep slopes (4-9%). Total P concentration was also similar with CT at sites under prolonged NT duration (~10 yr) and at NT fields planted with soybean [ (L.) Merr.]. Our results underscore the need to consider the covarying physical and management factors when assessing the potential of NT farming in controlling P loss in the environment. The limited impact of NT on dissolved P loss remains a serious impediment toward harnessing the water quality benefits of this management practice. PMID- 28991966 TI - Greenhouse Gas Emissions after Application of Landfilled Paper Mill Sludge for Land Reclamation of a Nonacidic Mine Tailings Site. AB - Large areas of mine tailings are reclaimed by applying organic amendments such as paper mill sludge (PMS). Although mining industries can use PMS freshly generated by paper mills, operational constraints on paper industries make temporary landfilling of this material an unavoidable alternative for the paper industries, creating the most prominent PMS source for mining industries. This study aimed to quantify soil greenhouse gas (GHG) emissions (NO, CO, and CH) after application of landfilled PMS (LPMS; i.e., excavated from a landfill site at a paper mill) and LPMS combined with a seeding treatment of white clover ( L.) on nonacidic mine tailings site prior to reforestation. Soil NO, CO, and CH fluxes were measured after applications of 50 and 100 Mg dry LPMS ha during two consecutive snow-free seasons on two adjacent sites; LPMS was applied once in the first season. The LPMS application increased NO emissions (7.6 to 34.7 kg NO-N ha, comprising 1.04 to 2.43% of applied N) compared with the unamended control during the first season; these emissions were negligible during the second season. The LPMS application increased CO emissions (~5800 to 11,400 kg CO-C ha, comprising 7 to 27% of applied C) compared with the unamended control on both sites and in both seasons. Fluxes of CH were negligible. White clover combined with LPMS treatments did not affect soil GHG emissions. These new GHG emission factors should be integrated into life-cycle analyses to evaluate the C footprint of potential symbioses between the mining and paper industries. Future research should focus on the effect of PMS applications on soil GHG emissions from a variety of mine tailings under various management practices and climatic conditions to plan responsible and sustainable land reclamation. PMID- 28991968 TI - Assessing the Yield and Load of Contaminants with Stream Order: Would Policy Requiring Livestock to Be Fenced Out of High-Order Streams Decrease Catchment Contaminant Loads? AB - Catchment contaminant loads vary with stream order as catchment characteristics influence inputs and in-stream processing. However, the relative influence and policy significance of these characteristics across a number of contaminants and at a national scale is unclear. We modeled the significance of catchment characteristics (e.g., climate, topography, geology, land cover), as captured by a national-scale River Environment Classification (REC) system, and stream order in the estimation of contaminant yields. We used this model to test if potential regulation in New Zealand requiring livestock to be fenced off from large (high) order streams would substantially decrease catchment contaminant loads. Concentration and flow data for 1998 to 2009 were used to calculate catchment load and yields of nitrogen (N) and phosphorus (P) species, suspended sediment, and at 728 water quality monitoring sites. On average, the yields of all contaminants increased with increasing stream order in catchments dominated by agriculture (generally lowland and pastoral REC land cover classes). Loads from low-order small streams (<1 m wide, 30 cm deep, and in flat catchments dominated by pasture) exempt from potential fencing regulations accounted for an average of 77% of the national load (varying from 73% for total N to 84% for dissolved reactive P). This means that to substantially reduce contaminant losses, other mitigations should be investigated in small streams, particularly where fencing of larger streams has low efficacy. PMID- 28991967 TI - Within-House Spatial Distribution of Fecal Indicator Bacteria in Poultry Litter. AB - Land application of poultry litter is often considered to be a major source of water pollutants in poultry-producing regions. However, reported levels of fecal indicator microorganisms in litter vary widely, with considerable variation possible within houses and across farms, depending on management practices. Therefore, a study was conducted to determine the levels and distribution of indicator microorganisms within 12 broiler farms representing three companies. Within each house, litter samples were collected from around the feed line, water line, north wall, cool pad end, middle, and fan end. Litter moisture content was significantly different within the houses, with the litter being driest around the feed line (19.8%) and wettest around the water line (40.7%). Mean levels of total coliforms, , enterococci, and were 3.7, 3.3, 6.4, and 4.0 log colony forming units g dry litter, respectively. Levels of total coliforms, , and were positively correlated with litter moisture content, but enterococci levels were not. Consequently, levels of total coliforms, , and , as well as enterococci, were highest around the water line and lowest around the feed line. These results indicate that areas with higher litter water content are more likely to contain higher levels of most fecal indicator microorganisms. Approaches to reduce litter water content in these areas would not only benefit the microbial quality of litter for land application but would also likely improve in-house disease control. PMID- 28991969 TI - Photosensitized Degradation of Amitriptyline and Its Active Metabolite Nortriptyline in Aqueous Fulvic Acid Solution. AB - Amitriptyline is a frequently prescribed tricyclic antidepressant. Although amitriptyline and its active metabolite, nortriptyline, have been widely detected in natural waters, their environmental fate due to photodegradation is poorly understood. Here we describe a study conducted to investigate the photodegradation of amitriptyline and its active metabolite under simulated sunlight. Neither amitriptyline nor nortriptyline underwent direct photodegradation, but rapid photosensitized degradation did occur in fulvic acid (FA) solutions. The photodegradation of amitriptyline and nortriptyline followed pseudo-first-order kinetics with rate constants 0.24 and 0.16 h, respectively, at pH 8.0 in air-saturated FA solutions. The photodegradation of the substrates increased markedly with pH. The deprotonation of amitriptyline and nortriptyline facilitated the availability of nonbonding electrons on nitrogen (N-electrons). The excited triplet state of FA (FA*) was verified as the main reactive species responsible for the photosensitized degradation. An electron transfer mechanism for the interaction between substrates and FA* was proposed on the basis of a series of quenching experiments, kinetic model and photoproducts determination. Demethylation at the alpha-carbon of amine and hydroxylation were two primary photochemical processes initiated by the electron transfer reaction in the air saturated FA solution; these were followed by generation of demethyl amine and mono-hydroxylation isomers. Our results suggest that indirect photodegradation is an important elimination process for amitriptyline and its active metabolite in natural waters. PMID- 28991970 TI - Identification of Factors Affecting Fecal Pollution in Beaver Lake Reservoir. AB - Standard methods for the evaluation of recreational water quality rely on generic bacterial indicators such as . However, does not provide enough information to determine fecal source or public health risk. The stsudy objective was to determine factors influencing the presence of and host-specific markers (HSM) from upstream to downstream in Beaver Lake Reservoir (BLR). From February 2014 to September 2015, 420 base flow and rain event samples were collected from seven sites-two sites from streams (White River [WR] and War Eagle Creek) draining into BLR and five sites from within BLR. Each sample was analyzed for and by quantitative polymerase chain reaction for HSM related to human, bovine, and poultry. The data indicate that overall levels of were significantly greater in the WR and significantly lower at the most downstream sampling location in BLR. is more likely present during spring (adjusted odds ratio [aOR] = 1.86), at the WR sampling site (aOR = 3.39), or during a rain event (aOR = 2.73). Moreover, the HSM HumM2 is more likely present (aOR = 1.99) when is present. These same factors were associated with concentrations >126 most probable number 100 mL (aOR = 2.76 12.48), except the poultry marker CL was more likely associated (aOR = 3.81) than HumM2. This study revealed that both seasonal and locational factors are important variables for fecal pollution in BLR. Moreover, these same factors may apply to fecal pollution in manmade reservoirs within similar types of watersheds across the United States, as well as internationally. PMID- 28991962 TI - Redox-active nanomaterials for nanomedicine applications. AB - Nanomedicine utilizes the remarkable properties of nanomaterials for the diagnosis, treatment, and prevention of disease. Many of these nanomaterials have been shown to have robust antioxidative properties, potentially functioning as strong scavengers of reactive oxygen species. Conversely, several nanomaterials have also been shown to promote the generation of reactive oxygen species, which may precipitate the onset of oxidative stress, a state that is thought to contribute to the development of a variety of adverse conditions. As such, the impacts of nanomaterials on biological entities are often associated with and influenced by their specific redox properties. In this review, we overview several classes of nanomaterials that have been or projected to be used across a wide range of biomedical applications, with discussion focusing on their unique redox properties. Nanomaterials examined include iron, cerium, and titanium metal oxide nanoparticles, gold, silver, and selenium nanoparticles, and various nanoscale carbon allotropes such as graphene, carbon nanotubes, fullerenes, and their derivatives/variations. Principal topics of discussion include the chemical mechanisms by which the nanomaterials directly interact with biological entities and the biological cascades that are thus indirectly impacted. Selected case studies highlighting the redox properties of nanomaterials and how they affect biological responses are used to exemplify the biologically-relevant redox mechanisms for each of the described nanomaterials. PMID- 28991971 TI - Effects of Positively Charged Dicyandiamide and Nitrogen Fertilizer Sources on Nitrous Oxide Emissions in Irrigated Corn. AB - Synthetic nitrogen (N) fertilizer formulations vary in their effects as substrates on nitrous oxide (NO) emissions. Mitigation of NO emissions can potentially be achieved through appropriate choice of N fertilizer sources combined with stabilizers. The effects of three N fertilizers and urease and nitrification inhibitors on NO emissions, crop N uptake, and yields were determined in a furrow-irrigated corn ( L.) system in Reiff loam soil in the Sacramento Valley of California for one growing season. Aqua ammonia (Aq. NH), urea ammonium nitrate (UAN), and calcium nitrate were sidedressed at the rate of 202 kg N ha. The control treatment received only starter fertilizer (20 kg N ha). Total seasonal emissions were in the order Aq. NH > UAN > calcium nitrate = control with 1.38, 0.97, 0.35, and 0.27 kg NO-N ha, respectively. A novel, positively charged form of dicyandiamide, KAS-771G77 (G77), was combined with Aq. NH and UAN to test the effectiveness of this nitrification inhibitor in reducing NO emissions. When combined with Aq. NH, G77 did not reduce the emissions, but G77 significantly lowered them in the UAN treatment. A similar reduction of NO emissions in the UAN treatment was achieved with the urease and nitrification inhibitor AgrotainPlus. Yields and N use efficiency did not differ among the fertilized treatments. Ammoniacal fertilizers had higher NO emissions than nitrate-based fertilizers, which could imply nitrification pathways as a source of NO emissions. The use of G77 or AgrotainPlus, when applied with UAN, was an effective NO mitigation practice. PMID- 28991972 TI - Comparison of N2O Emissions and Gene Abundances between Wastewater Nitrogen Removal Systems. AB - Biological nitrogen removal (BNR) systems are increasingly used in the United States in both centralized wastewater treatment plants (WWTPs) and decentralized advanced onsite wastewater treatment systems (OWTS) to reduce N discharged in wastewater effluent. However, the potential for BNR systems to be sources of nitrous oxide (NO), a potent greenhouse gas, needs to be evaluated to assess their environmental impact. We quantified and compared NO emissions from BNR systems at a WWTP (Field's Point, Providence, RI) and three types of advanced OWTS (Orenco Advantex AX 20, SeptiTech Series D, and Bio-Microbics MicroFAST) in nine Rhode Island residences ( = 3 per type) using cavity ring-down spectroscopy. We also used quantitative polymerase chain reaction to determine the abundance of genes from nitrifying () and denitrifying () microorganisms that may be producing NO in these systems. Nitrous oxide fluxes ranged from -4 * 10 to 3 * 10 umol NO m s and in general followed the order: centralized WWTP > Advantex > SeptiTech > FAST. In contrast, when NO emissions were normalized by population served and area of treatment tanks, all systems had overlapping ranges. In general, the emissions of NO accounted for a small fraction (<1%) of N removed. There was no significant relationship between the abundance of or genes and NO emissions. This preliminary analysis highlights the need to evaluate NO emissions from wastewater systems as a wider range of technologies are adopted. A better understanding of the mechanisms of NO emissions will also allow us to better manage systems to minimize emissions. PMID- 28991975 TI - The Relationship between Land Use and Vulnerability to Nitrogen and Phosphorus Pollution in an Urban Watershed. PMID- 28991973 TI - Determining the Effect of Drying Time on Phosphorus Solubilization from Three Agricultural Soils under Climate Change Scenarios. AB - Climate projections for the future indicate that the United Kingdom will experience hotter, drier summers and warmer, wetter winters, bringing longer dry periods followed by rewetting. This will result in changes in phosphorus (P) mobilization patterns that will influence the transfer of P from land to water. We tested the hypothesis that changes in the future patterns of drying-rewetting will affect the amount of soluble reactive phosphorus (SRP) solubilized from soil. Estimations of dry period characteristics (duration and temperature) under current and predicted climate were determined using data from the UK Climate Projections (UKCP09) Weather Generator tool. Three soils (sieved <2 mm), collected from two regions of the United Kingdom with different soils and farm systems, were dried at 25 degrees C for periods of 0, 2, 4, 5, 6, 8, 10, 15, 20, 25, 30, 60, and 90 d, then subsequently rewetted (50 mL over 2 h). The solubilized leachate was collected and analyzed for SRP. In the 2050s, warm period temperature extremes >25 degrees C are predicted in some places and dry periods of 30 to 90 d extremes are predicted. Combining the frequency of projected dry periods with the SRP concentration in leachate suggests that this may result overall in increased mobilization of P; however, critical breakpoints of 6.9 to 14.5 d dry occur wherein up to 28% more SRP can be solubilized following a rapid rewetting event. The precise cause of this increase could not be identified and warrants further investigation as the process is not currently included in P transfer models. PMID- 28991974 TI - Laboratory Column Evaluation of High Explosives Attenuation in Grenade Range Soils. AB - High explosives (HEs) deposited on military ranges can leach through the soil and contaminate groundwater. We examined the transport and fate of HEs in laboratory columns containing soils from two hand grenade bays (Bays C and T) and the impact of organic amendments on biodegradation. Soil characteristics were similar; however, Bay C had somewhat higher clay and organic C. Experimental treatments included addition of crude glycerin and lignosulfonate, and parallel control columns. Experimental results showed extensive 2,4,6-trinitrotoluene (TNT) degradation with minimal leaching, consistent with prior batch microcosm results. Amendment addition enhanced TNT degradation in both Bays C and T compared with controls. Although hexahydro-1,3,5-trinitro-1,3,5-triazine (Royal Demolition Explosive, or RDX) did not biodegrade in prior aerobic batch microcosms, 64 to 77% of RDX biodegraded in untreated soil columns with O present in the mobile soil gas. The RDX biodegradation was likely associated with short-term anoxic conditions or anoxic micro-niches. In nearly saturated Bay C columns, RDX removal increased to >92%. Amendment addition to unsaturated Bay T columns increased RDX removal to >86%. In one column, the soil remained anoxic (O < 5% by volume) for about a year after amendment addition, significantly reducing RDX leaching. Nitroso degradation products were produced equivalent to 9 to 39% of the RDX degraded, with most retained in the soil (9-37%) and 0 to 3% in the effluent. These results demonstrate that RDX biodegradation can occur in soils with measurable O, and that amendment addition can reduce RDX leaching by stimulating anaerobic biodegradation. PMID- 28991976 TI - Combining Urease and Nitrification Inhibitors with Incorporation Reduces Ammonia and Nitrous Oxide Emissions and Increases Corn Yields. AB - Less than 50% of applied nitrogen (N) fertilizer is typically recovered by corn ( L.) due to climatic constraints, soil degradation, overapplication, and losses to air and water. Two application methods, two N sources, and two inhibitors were evaluated to reduce N losses and enhance crop uptake. The treatments included broadcast urea (BrUrea), BrUrea with a urease inhibitor (BrUrea+UI), BrUrea with a urease and a nitrification inhibitor (BrUrea+UI+NI), injection of urea ammonium nitrate (InjUAN), and injected with one or both inhibitors (InjUAN+UI, InjUAN+UI+NI), and a control. The BrUrea treatment lost 50% (64.4 kg N ha) of the applied N due to ammonia volatilization, but losses were reduced by 64% with BrUrea+UI+NI (23.0 kg N ha) and by 60% with InjUAN (26.1 kg N ha). Ammonia losses were lower and crop yields were greater in 2014 than 2013 as a result of the more favorable weather when N was applied in 2014. When ammonia volatilization was reduced by adding a urease inhibitor, NO emissions were increased by 30 to 31% with BrUrea+UI and InjUAN+UI compared with BrUrea and InjUAN, respectively. Pollution swapping was avoided when both inhibitors were used (BrUrea+UI+NI, InjUAN+UI+NI) as both ammonia volatilization and NO emissions were reduced, and corn grain yields increased by 5% with BrUrea+UI+NI and by 7% with InjUAN+UI+NI compared with BrUrea and InjUAN, respectively. The combination of two N management strategies (InjUAN+UI+NI) increased yields by 19% (12.9 t ha) compared with BrUrea (10.8 t ha). PMID- 28991977 TI - Structural Equation Model of Total Phosphorus Loads in the Red River of the North Basin, USA and Canada. AB - Attribution of the causes of trends in nutrient loading is often limited to correlation, qualitative reasoning, or references to the work of others. This paper represents efforts to improve causal attribution of water-quality changes. The Red River of the North basin provides a regional test case because of international interest in the reduction of total phosphorus loads and the availability of long-term total phosphorus data and ancillary geospatial data with the potential to explain changes in water quality over time. The objectives of the study are to investigate structural equation modeling methods for application to water-quality problems and to test causal hypotheses related to the drivers of total phosphorus loads over the period 1970 to 2012. Multiple working hypotheses that explain total phosphorus loads and methods for estimating missing ancillary data were developed, and water-quality related challenges to structural equation modeling (including skewed data and scaling issues) were addressed. The model indicates that increased precipitation in season 1 (November February) or season 2 (March-June) would increase total phosphorus loads in the basin. The effect of agricultural practices on total phosphorus loads was significant, although the effect is about one-third of the effect of season 1 precipitation. The structural equation model representing loads at six sites in the basin shows that climate and agricultural practices explain almost 60% of the annual total phosphorus load in the Red River of the North basin. The modeling process and the unexplained variance highlight the need for better ancillary long term data for causal assessments. PMID- 28991978 TI - Solute Transport Properties of Fen Peat Differing in Organic Matter Content. AB - There is a limited understanding of solute transport properties of degraded peat soils as compared to mineral substrates. A lower organic matter (OM) content is often the result of peat degradation and mineralization following artificial drainage. In this study, we aimed at deducing changes in solute transport properties of peat soils differing in OM content. Miscible displacement experiments were conducted on 70 undisturbed soil columns with OM contents ranging from 11 to 86% w/w under saturated steady-state conditions using tritium and bromide as conservative tracers. Measured breakthrough curves (BTCs) were subjected to model analysis using three different approaches: single-porosity model (SPM), mobile-immobile model (MIM), and two-flow region model (TFRM). The results indicated that (i) nonequilibrium solute transport processes are common in peat soils; (ii) the TFRM improved predictions of BTCs with heavy tailing or two peaks; (iii) applied tracers, tritium and bromide, were retarded in peat soils with higher OM content; and (iv) pronounced preferential flow mainly occurred in peat soils with lower OM content. This type of strong preferential flow had a small ratio of measured to fitted pore water velocity and a greater ratio of velocities (/ > 3.0) in the fast and slow transport region as obtained from the TFRM. We conclude that shallow groundwater resources are more likely to become polluted in drained and degraded fen peats that are used for agricultural purposes. PMID- 28991979 TI - Pathogen Survey of Pulp and Paper Mill Biosolids Compared with Soils, Composts, and Sewage Biosolids. AB - Regulatory policies to manage land application of organic materials are risk based, with focus on the quality of these residuals. The Ontario Ministry of the Environment and Climate Change (MOECC) determined that limited information was available on pulp and paper biosolids (PPB) with respect to human enteric pathogens. To address this data gap, MOECC conducted an extensive survey (2005 2006) across Ontario to characterize the microbiological quality of PPB. Quantitative testing was performed for fecal indicators (, enterococci, ) and enteric pathogens (, , , and ) using matrix-validated methods. Comparative benchmark materials (soils and soil amendments) were analyzed concurrently for risk comparison. Results showed that detection rates in PPB were low, 5 to 25% for pathogens and <55% for . , and were found at low frequency (6-8% of samples) and at low mean concentrations (2 most probable number g dry wt., 9 oocysts g dry wt., and 7 cells g dry wt., respectively). was more frequently observed (19% of samples), with a mean of 30 cysts g dry wt. Pathogen concentrations in PPB were generally equivalent to or higher than those in soils, composts, and pelletized sewage biosolids but significantly lower than in sewage biosolids. levels exceeded standards (1000 colony-forming units g dry wt.) in one-third of samples, most often in fresh PPB rather than stored and lagoon solids. Microbial quality of PPB across all surveyed mills tended to be variable and sector- and/or site specific but in many cases would not consistently meet Canadian federal fertilizers standards. These findings were important to inform Ontario's nutrient management regulations, supporting classification of PPB as higher pathogen risk than compost and commercial fertilizers. PMID- 28991980 TI - Biogas Digester Hydraulic Retention Time Affects Oxygen Consumption Patterns and Greenhouse Gas Emissions after Application of Digestate to Soil. AB - Knowledge about environmental impacts associated with the application of anaerobic digestion residue to agricultural land is of interest owing to the rapid proliferation of biogas plants worldwide. However, virtually no information exists concerning how soil-emitted NO is affected by the feedstock hydraulic retention time (HRT) in the biogas digester. Here, the O planar optode technique was used to visualize soil O dynamics following the surface application of digestates of the codigestion of pig slurry and agro-industrial waste. We also used NO isotopomer analysis of soil-emitted NO to determine the NO production pathways, i.e., nitrification or denitrification. Two-dimensional images of soil O indicated that anoxic and hypoxic conditions developed at 2.0- and 1.5-cm soil depth for soil amended with the digestate produced with 15-d (PO15) and 30-d (PO30) retention time, respectively. Total NO emissions were significantly lower for PO15 than PO30 due to the greater expansion of the anoxic zone, which enhanced NO reduction via complete denitrification. However, cumulative CO emissions were not significantly different between PO15 and PO30 for the entire incubation period. During incubation, NO emissions came from both nitrification and denitrification in amended soils. Increasing the HRT of the biogas digester appears to induce significant NO emissions, but it is unlikely to affect the NO production pathways after application to soil. PMID- 28991981 TI - Denitrification along the Stream-Riparian Continuum in Restored and Unrestored Agricultural Streams. AB - Although floodplain restoration may improve stream-riparian connectivity and increase channel stability through cross-vane installation, stream bank regrading, and buffer revegetation, the impact of these geomorphic alterations on denitrification across the aquatic-terrestrial interface is poorly understood. Seasonal denitrification enzyme activity (DEA) was compared in stream-riparian ecotones of four streams with varying hydrologic connection, riparian vegetation composition, and agricultural influence. Riparian and stream DEA was generally higher in sites adjacent to agricultural fields due to proximity to nitrate source. Mean DEA was higher in the dormant season (riparian: 928 +/- 116 ng N g dry mass [DM] h, stream: 108 +/- 149 ng N g DM h) than in the growing season (riparian: 355 +/- 55 ng N g DM h, stream: 45 +/- 40 ng N g DM h) and was influenced by antecedent precipitation, soil texture, and landscape characteristics (land use, vegetation type, topography) in multivariate models. Hot spots of denitrification occurred at the confluence of fine soil textures with high organic matter and moisture, often at low-lying areas of the landscape. At the restored site, we observed enhanced denitrification in the reconnected floodplain but decreased stream denitrification capacity in pools. Across all sites, streams had lower DEA than riparian zones, stressing the importance of restoration approaches designed to conserve riparian areas and maintain hydrologic connectivity. Easily obtainable data including precipitation, adjacent land use, vegetation, and stream and floodplain geomorphology reasonably predicted denitrification potential compared with more complex models, showing potential for application in water resources and nitrogen management. PMID- 28991982 TI - Ammonia Oxidizers in a Grazing Land with a History of Poultry Litter Application. AB - Poultry litter (PL) is widely applied on grazing lands in Georgia. However, it is not clear how its long-term use affects soil microorganisms and their function. We examined changes in activity and community structure of ammonia-oxidizing archaea (AOA) and bacteria (AOB) in a grazing land with a history of PL application and compared it to treatment with urea ammonium nitrate (UAN). Soil samples (0-15 cm) were collected in 2009 (after 15 yr of PL application) and in 2013 (after 2 yr of no application). The abundance and community composition of ammonia oxidizers (AO) were determined with molecular techniques that targeted Nitrification potential (NP) was used for measuring their activity. Abundance of AO was significantly higher in PL (7.41 and 7.10 log copies g soil for AOB and AOA, respectively) than in UAN plots (6.82 and 6.50 log copies g soil for AOB and AOA, respectively) in 2009. This is consistent with NP, which was higher in PL (0.78 mg NO -N kg h) than in UAN (0.50 mg NO-N kg h) plots in 2009. The abundance of AO and NP decreased in 2013. There was no treatment effect on the composition of AO. Correlation analysis suggested that AOB were functionally more important than AOA, indicating the need to target AOB for efficient management of N in PL receiving soils. Overall, the difference in nitrification between PL and UAN was mainly caused by the change in AO abundance rather than composition, and AO were not negatively affected by an increase in PL-derived trace metal concentrations. PMID- 28991983 TI - Natural and Enhanced Attenuation of Explosives on a Hand Grenade Range. AB - 2,4,6-Trinitrotoluene (TNT) and hexahydro-1,3,5-trinitro-1,3,5-triazine (Royal Demolition Explosive, or RDX) deposited on hand grenade training ranges can leach through the soil and impact shallow groundwater. A 27-mo field monitoring project was conducted to evaluate the transport and attenuation of high explosives in variably saturated soils at an active grenade range located at Fort Bragg, NC. Two approaches were evaluated: (i) natural attenuation in grenade Bay C; and (ii) enhanced attenuation in Grenade Bay T. There was no evidence of TNT accumulation or leaching in surface soils or pore water in either bay, consistent with parallel laboratory studies showing aerobic and anaerobic biodegradation of TNT. In the untreated Bay C, the low saturated hydraulic conductivity () combined with high rainfall and warm summer temperatures resulted in reducing conditions (low oxidation-reduction potential), an increase in dissolved Mn, and a rapid decline in nitrate and RDX. In Bay T, the somewhat greater and lower soil organic C level resulted in more oxidizing conditions with greater RDX leaching. A single-spray application of glycerin and lignosulfonate to the soil surface in Bay T was effective in generating reducing conditions and stimulating RDX biodegradation for ~1 yr. PMID- 28991984 TI - Role of Dissolved Organic Matter in the Release of Chromium from Schwertmannite: Kinetics, Repartition, and Mechanisms. AB - Dissolved organic matter (DOM) is an important factor influencing mineral biogeochemistry, although the role of labile DOM in the release of chromium (Cr) from schwertmannite, a mineral with high surface area, is unclear. In this study, the interaction of DOM with synthetic CrO-schwertmannite was investigated to better understand the potential fate of Cr in high-DOM environments. Minerals and their products were analyzed using Fourier transform infrared spectroscopy, X-ray diffraction, transmission electron microscopy, scanning electron microscopy, and X-ray photoelectron spectroscopy. Experiments were conducted at pH 3.2 or 6.5 for different lengths of time, with a shrinking core model developed to describe kinetic processes. The concentration of total Cr in solution reached a maximum when the pH was 6.5 and the concentration of L-tryptophan was 5 mM. The newly formed minerals were confirmed to be mixtures involving residual schwertmannite, goethite, ferrihydrite, and jarosite. A possible mechanism is proposed to be a ligand-controlled binary system, accompanied by possible reduction at acidic pH conditions (3.2), including mass transfer and charge transfer processes. This study gives a new perspective for understanding the reactivity and stability of schwertmannite in the environment; it also provides some predictions on the mobility and fate of Cr. These findings will help design remediation strategies for Cr contamination. PMID- 28991986 TI - Tile Drainage Nitrate Losses and Corn Yield Response to Fall and Spring Nitrogen Management. AB - Nitrogen (N) management strategies that maintain high crop productivity with reduced water quality impacts are needed for tile-drained landscapes of the US Midwest. The objectives of this study were to determine the effect of N application rate, timing, and fall nitrapyrin addition on tile drainage nitrate losses, corn ( L.) yield, N recovery efficiency, and postharvest soil nitrate content over 3 yr in a corn-soybean [ (L.) Merr.] rotation. In addition to an unfertilized control, the following eight N treatments were applied as anhydrous ammonia in a replicated, field-scale experiment with both corn and soybean phases present each year in Illinois: fall and spring applications of 78, 156, and 234 kg N ha, fall application of 156 kg N ha + nitrapyrin, and sidedress (V5-V6) application of 156 kg N ha. Across the 3-yr study period, increases in flow weighted NO concentrations were found with increasing N rate for fall and spring N applications, whereas N load results were variable. At the same N rate, spring vs. fall N applications reduced flow-weighted NO concentrations only in the corn soybean-corn rotation. Fall nitrapyrin and sidedress N treatments did not decrease flo8w-weighted NO concentrations in either rotation compared with fall and spring N applications, respectively, or increase corn yield, crop N uptake, or N recovery efficiency in any year. This study indicates that compared with fall N application, spring and sidedress N applications (for corn-soybean-corn) and sidedress N applications (for soybean-corn-soybean) reduced 3-yr mean flow weighted NO concentrations while maintaining yields. PMID- 28991985 TI - Frequent Prescribed Burning as a Long-term Practice in Longleaf Pine Forests Does Not Affect Detrital Chemical Composition. AB - The O horizon, or detrital layer, of forest soils is linked to long-term forest productivity and health. Fuel reduction techniques, such as prescribed fire, can alter the thickness and composition of this essential ecosystem component. Developing an understanding of the changes in the chemical composition of forest detritus due to prescribed fire is essential for forest managers and stakeholders seeking sustainable, resilient, and productive ecosystems. In this study, we evaluated fuel quantity, fuel structure, and detrital chemical composition in longleaf pine ( Miller) forests that have been frequently burned for the last 40 yr at the Tom Yawkey Wildlife Center in Georgetown, SC. Our results suggest that frequent prescribed fire reduces forest fuel quantity ( < 0.01) and vertical structure ( = 0.01). Using pyrolysis-gas chromatography/mass spectrometry as a molecular technique to analyze detrital chemical composition, including aromatic compounds and polycyclic aromatic hydrocarbons, we found that the chemical composition of forest detritus was nearly uniform for both unburned and burned detritus. Our burning activities varied in the short term, consisting of annual dormant, annual growing, and biennial dormant season burns. Seasonal distinctions were present for fuel quantity and vertical fuel structure, but these differences were not noted for the benzene/phenol ratio. These results are significant as more managers consider burning existing longleaf stands while determining effective management practices for longleaf stands yet to be established. Managers of such stands can be confident that frequent, low-intensity, low severity prescribed burns in longleaf pine forests do little to affect the long term chemical composition of forest detritus. PMID- 28991987 TI - Predictors of Phosphorus Leaching from Bioretention Soil Media. AB - The phosphorus saturation index (PSI) and P saturation ratio (PSR) were tested across a wide range of bioretention soil mixtures (BSMs) for their relationship to total and dissolved P in column leachate. The BSMs tested were made using different feedstocks including sand alone, food and yard waste compost, biosolids and yard compost, and high Fe biosolids. The PSI of the mixtures ranged from 0.23 +/- 0.03 (biosolids and yard waste compost 15%, oyster shells 5%) to 1.26 +/- 0.02 (biosolids and yard waste compost 80%). The PSR of the mixtures ranged from 0.05 +/- 0 (100% sand) to 3.12 +/- 0.12 (biosolids and yard waste compost 80%). A total of 12 storm events were staged using both synthetic rainwater (total P = 1.71 +/- 0.3 mg L) and actual stormwater (total P = 0.08 +/- 0.03 mg L). Excluding the sand-only mixture, all treatments were a source of P for the duration of the study. However both total and dissolved P concentrations decreased over time. Effluent concentrations of total P in the first event ranged from 0.59 to 75.55 mg L but decreased by the final event to between 0.15 and 10.73 mg L. The PSR was found to be a good predictor of P leaching from all BSMs with an of 0.73 for total mass of P leached across all leaching events. The PSI was a poor predictor ( < 0.3). The PSR also predicted total P in leachate for individual events more effectively than the PSI. Total P in the BSMs had no relationship to P in the leachate. PMID- 28991988 TI - Citrate Addition Increased Phosphorus Bioavailability and Enhanced Gasoline Bioremediation. AB - Phosphorus (P) bioavailability often limits gasoline biodegradation in calcareous cold-region soils. One possible method to increase P bioavailability in such soils is the addition of citrate. Citrate addition at the field scale may increase hydrocarbon degradation by: (i) enhancing inorganic and organic P dissolution and desorption, (ii) increasing hydrocarbon bioavailability, and/or (iii) stimulating microbial activity. Alternatively, citrate addition may inhibit activity due to competitive effects on carbon metabolism. Using a field-scale in situ biostimulation study, we evaluated if citrate could stimulate gasoline degradation and what the dominant mechanism of this stimulation will be. Two large bore injectors were constructed at a site contaminated with gasoline, and a biostimulation solution of 11 mM MgSO, 1 mM HPO, and 0.08 mM HNO at pH 6.5 in municipal potable water was injected at ~5000 L d for about 4 mo. Following this, 10 mM citric acid was incorporated into the existing biostimulation solution and the site continued to be stimulated for 8 mo. After citrate addition, the bioavailable P fraction in groundwater and soil increased. Iron(II) groundwater concentrations increased and corresponded to decreases in benzene, toluene, ethylbenzene, xylenes (BTEX) in groundwater, as well as a decrease in F1 in the soil saturated zone. Overall, citrate addition increased P bioavailability and may stimulate anaerobic microbial activity, resulting in accelerated anaerobic gasoline bioremediation in cold-region calcareous soils. PMID- 28991989 TI - Impact of Roadway Stormwater Runoff on Microbial Contamination in the Receiving Stream. AB - Stormwater runoff from roadways has increasingly become a regulatory concern for water pollution control. Recent work has suggested roadway stormwater runoff as a potential source of microbial pollutants. The objective of this study was to determine the impact of roadway runoff on the microbiological quality of receiving streams. Microbiological quality of roadway stormwater runoff and the receiving stream was monitored during storm events with both cultivation dependent fecal bacteria enumeration and cultivation-independent high-throughput sequencing techniques. Enumeration of total coliforms as a measure of fecal microbial pollution found consistently lower total coliform counts in roadway runoff than those in the stream water, suggesting that roadway runoff was not a major contributor of microbial pollutants to the receiving stream. Further characterization of the microbial community in the stormwater samples by 16S ribosomal RNA gene-based high-throughput amplicon sequencing revealed significant differences in the microbial composition of stormwater runoff from the roadways and the receiving stream. The differences in microbial composition between the roadway runoff and stream water demonstrate that roadway runoff did not appear to have a major influence on the stream in terms of microbiological quality. Thus, results from both fecal bacteria enumeration and high-throughput amplicon sequencing techniques were consistent that roadway stormwater runoff was not the primary contributor of microbial loading to the stream. Further studies of additional watersheds with distinct characteristics are needed to validate these findings. Understanding gained in this study could support the development of more effective strategies for stormwater management in sensitive watersheds. PMID- 28991990 TI - Narasin effects on energy, nutrient, and fiber digestibility in corn-soybean meal or corn-soybean meal-dried distillers grains with solubles diets fed to 16-, 92-, and 141-kg pigs. AB - Three experiments were conducted to determine the effect of narasin on growth performance and on GE and nutrient digestibility in nursery, grower, and finishing pigs fed either a corn-soybean meal (CSBM) diet or a CSBM diet supplemented with distillers dried grains with solubles (DDGS), in combination with either 0 or 30 mg narasin/kg of diet. In Exp. 1 (64 gilts, initial BW = 9.0 kg, SD = 1.0 kg) and Exp. 2 (60 gilts. initial BW = 81.1 kg, SD = 6.1 kg), gilts were allotted into individual pens and fed their experimental diets for 24 and 21 d, respectively. On the last 2 d of each experiment, fecal samples were collected to assess apparent total tract digestibility (ATTD) of GE and various nutrients. In Exp. 3, 2 separate groups of 24 gilts (initial BW = 145.1 kg, SD = 7.8 kg) were allotted to individual metabolism crates and fed their experimental diets for 30 d prior to a time-based 6-d total fecal collection period to assess GE and nutrient digestibility. In Exp. 1, there was an interaction between diet type and narasin addition for G:F and for many of the ATTD coefficients measured. When narasin was supplemented to the CSBM diet, ATTD of GE, DM, C, S, phosphorus, NDF, and ADF was either not changed or reduced, while when narasin was supplemented to DDGS diets, these same ATTD parameters were increased (interaction, <= 0.05). Even though ADG and ADFI were not affected, G:F was improved in pigs fed the CSBM diet with supplemental narasin, but was reduced in pigs fed the DDGS diet with supplemental narasin (interaction, < 0.05). In Exp. 2, there was an interaction between diet type and narasin supplementation only for ATTD of Ca (interaction, < 0.01), in that narasin supplementation did not change the ATTD of Ca in pigs fed the CSBM diet, while narasin supplementation reduced the ATTD of Ca in pigs fed the DDGS containing diet. In Exp. 3, there was an interaction between diet and narasin only for ATTD of C (interaction, < 0.01) in that narasin supplementation resulted in an increased ATTD of C in pigs fed the CSBM diet, while narasin supplementation to the DDGS containing diet resulted in a reduced ATTD of Ca. In general, the data indicate that narasin interacted with and had its largest effect on pig performance and GE or nutrient digestibility in 9 to 23 kg pigs compared to pigs weighing greater than 80 kg. The data also indicate that the addition of DDGS reduced GE, DM, Ca, and N digestibility, regardless of BW. PMID- 28991991 TI - Effects of ghrelin on nocturnal melatonin secretion in sheep: An in vitro and in vivo approach. AB - Recent studies confirmed that pineal melatonin (MEL) secretion is regulated by ghrelin (GHRL) in seasonally reproductive sheep. The first in vivo experiment investigated whether the effect of GHRL on nocturnal secretion of MEL in sheep is mediated by type 2 serotonin receptors. Sheep ( = 16) were intravenously injected with GHRL (2.5 MUg/kg of BW) and meta-Chlorophenylpiperazine (mCPP; a mixed agonist of 5-HT2B/5-HT2C receptors; 1 mg/kg BW), either combined or individually, during the short-day (SDS) and long-day (LDS) seasons. Blood samples were collected at 15-min intervals for 4 h. The second in vitro experiment examined the effect of GHRL (10 ng/mL) on MEL secretion by pineal gland (PG) explants incubated for 5 h. The expression levels and/or concentrations of tryptophan 5 hydroxylase 1 (TPH1), aralkylamine N-acetyltransferase (AA-NAT), and the phosphorylated form of AA-NAT (p31T-AA-NAT) were determined at selected time points during the SDS and LDS seasons. The experiments demonstrated that GHRL reduced MEL secretion ( < 0.01) during the SDS season. Administration of mCPP or a combination of GHRL + mCPP stimulated MEL secretion ( < 0.01) regardless of the season. Furthermore, GHRL regulated nightly MEL secretion in a TPH1-independent manner. However, during the SDS season, GHRL reduced p31T-AA-NAT expression and the AA-NAT concentration ( < 0.01) and inhibited MEL secretion ( < 0.001), whereas during the LDS season, GHRL had no effect on MEL secretion or on the expression of the examined enzymes. These findings indicate that GHRL directly and indirectly affects PG activity in sheep and that the photoperiod modulates the effects of GHRL. PMID- 28991992 TI - Sheep from low-methane-yield selection lines created on alfalfa pellets also have lower methane yield under pastoral farming conditions. AB - Selection lines of sheep with low and high CH yield (g/kg DMI; CH/DMI) are being developed on the basis of feeding pelleted alfalfa hay at 2.0 times maintenance ME requirements in respiration chambers, but their divergence under predominant grazing conditions, as in New Zealand, is not known. The objectives of this study were to determine CH emissions and rumen fermentation characteristics in sheep from low and high CH/DMI selection lines while grazing pasture. Two grazing experiments were conducted with 42 selection line ewes in March 2013 (Exp. 1) and 98 selection line progeny ewe hoggets in October/November 2014 (Exp. 2), with CH emissions estimated by the SF tracer technique and DMI estimated by titanium oxide in combination with natural long-chain -alkanes. Total daily CH production (g/d) was similar between high and low CH/DMI selection line sheep in Exp. 1 and lower for low CH/DMI progeny compared with high CH/DMI progeny in Exp. 2 ( < 0.05). The CH/DMI tended to be 20% lower for low CH/DMI line sheep compared with high CH/DMI selection line sheep in Exp. 1 ( < 0.10) and was 15% lower for the low CH/DMI line in Exp. 2 ( < 0.01). Total VFA concentration and concentrations (m) of acetate, butyrate, and isobutyrate plus isovalerate were lower ( < 0.05) for low CH/DMI line sheep compared with high CH/DMI selection line sheep in both experiments. The current study indicates that differences in CH/DMI and VFA concentrations in selection line sheep, previously established on alfalfa pellets, are also present to a similar magnitude when grazing pasture. PMID- 28991993 TI - Use of the spectrophotometric color method for the determination of the age of skin lesions on the pig carcass and its relationship with gene expression and histological and histochemical parameters. AB - The presence of lesions on the pig carcass is an indicator of poor animal welfare and has economic impact as it downgrades the carcass value. The assessment of the age of lesions on the carcass may help identify risk factors and ultimately prevent their occurrence. The aim of this study was to assess the age of lesions on pig carcasses through spectrophotometric color evaluation and to relate the results with gene expression and histological and histochemical parameters. A total of 96 barrows were mixed 4 times over 3 d before slaughter and 80 lesions were selected after skin lesion observations to define 4 age categories: < 7 h (T1), 7-25 h (T2), 25-30 h (T3), and 49-54 h (T4). A nonlesioned skin area was used as a control. At slaughter, 3 biopsies per lesion and control skin were taken immediately after bleeding for analyses of gene expression (, , , , , , , , , ), skin histological characteristics (inflammation, erosion or ulceration, and necrosis), and enzyme activity (alkaline phosphatase and adenosine triphosphatase). The number of lesions was counted on each carcass, and the color was assessed visually by a pictorial chart and instrumentally through a spectrophotometer. Delta values (Delta) were calculated as the difference between the value of the lesion and the value of the control for all measures, except for the histological analysis. Results indicated that visual color observation was not sufficiently accurate to discriminate lesions by time of infliction ( > 0.10), while the spectrophotometer DeltaL* and Deltaa* values variation allowed the identification of < 7 h or > 25 h old lesions ( < 0.05). Similarly, the expression of , , , , and genes was higher ( < 0.05) in < 7 h old lesions, while gene expression was higher ( < 0.05) in < 25 h old lesions. As for the histological analysis, the severity of inflammation was correlated with the age of the lesion (lower score in < 7 h old lesions and higher score in > 25 h old lesions; < 0.05). To conclude, the spectrophotometric color assessment of the carcass lesions at slaughter appears to be a reliable method to discriminate between fresh and older lesions on the carcass at the abattoir. PMID- 28991994 TI - Technical note: Validation of an automated system for monitoring and restricting water intake in group-housed beef steers. AB - The Insentec Roughage Intake Control (RIC) system has been validated for the collection of water intake; however, this system has not been validated for water restriction. The objective of this validation was to evaluate the agreement between direct observations and automated intakes collected by the RIC system under both ad libitum and restricted water conditions. A total of 239 crossbred steers were used in a 3-d validation trial, which assessed intake values generated by the RIC electronic intake monitoring system for both ad libitum water intake ( = 122; BASE) and restricted water intake ( = 117; RES). Direct human observations were collected on 4 Insentec water bins for three 24-h periods and three 12-h periods for BASE and RES, respectively. An intake event was noted by the observer when the electronic identification of the animal was read by the transponder and the gate lowered, and starting and ending bin weights were recorded for each intake event. Data from direct observations across each validation period were compared to automated observations generated from the RIC system. Missing beginning or ending weight values for visual observations occasionally occurred due to the observer being unable to capture the value before the monitor changed when bin activity was high. To estimate the impact of these missing values, analyses denoted as OBS were completed with the incomplete record coded as missing data. These analyses were contrasted with analyses where observations with a single missing beginning or end weight (but not both) were assumed to be identical to that which was recorded by the Insentec system (OBS). Difference in mean total intake across BASE steers was 0.60 +/- 2.06 kg OBS (0.54 +/- 1.99 kg OBS) greater for system observations than visual observations. The comparison of mean total intake across the 3 RES validation days was 0.53 +/- 2.30 kg OBS (0.13 +/- 1.83 kg OBS) greater for system observations than direct observations. Day was not a significant source of error in this study ( > 0.05). These results indicate that the system was capable of limiting water of individual animals with reasonable accuracy, although errors are slightly higher during water restriction than during ad libitum access. The Insentec system is a suitable resource for monitoring individual water intake of growing, group-housed steers under ad libitum and restricted water conditions. PMID- 28991995 TI - Energy and protein requirements for maintenance of dairy goats during pregnancy and their efficiencies of use. AB - It has been suggested that maintenance requirements are similar among animals of different physiological stages; however, important physiological changes occur in the maternal body during pregnancy. Therefore, the aim of this study was to determine the energy and protein requirements for the maintenance of pregnant dairy goats and to estimate their efficiency of energy and protein utilization for maintenance and pregnancy. We used 66 multiparous pregnant goats having 49.0 +/- 1.59 kg initial BW (around the third or fourth parturition) arranged in a randomized block design with a 3 * 3 factorial scheme including slaughter at different days of pregnancy (DOP; 80, 110, and 140 d) and feed restriction (0, 20, and 40% feed restriction). The comparative slaughter technique was used to estimate energy and protein maintenance requirements. Goats slaughtered at 140 DOP were subjected to digestibility trials at around 80, 110, and 140 DOP to estimate diet metabolizability and N balance (NBAL). Metabolizability decreased with feed restriction and was 63.3 +/- 2.16, 55.7 +/- 2.35, and 58.2 +/- 2.30% at 0, 20, and 40% of feed restriction, respectively ( < 0.01). There was no effect of DOP on NE or the requirements of ME for maintenance (ME), which were 197 and 315 kJ/kg empty body weight (EBW), respectively, and the efficiency of ME utilization for maintenance (k) was 0.63. Similarly, DOP did not affect thedaily net protein requirements for maintenance (NP) estimated using the comparative slaughter technique (1.38 +/- 0.512 g/kg EBW; = 0.003) or the NP estimated using NBAL (2.49 +/- 0.594 g/kg EBW; < 0.01). The MP requirement for maintenance (MP) estimated using the comparative slaughter technique was not affected by DOP and was 3.22 g MP/kg EBW ( < 0.01). The efficiency of MP utilization for maintenance (k) was 0.43. The efficiency of ME utilization for pregnancy (k) increased with the progress of pregnancy and was 0.058, 0.10, and 0.19 at 80, 110, and 140 DOP, respectively. Similarly, the efficiency of MP utilization for pregnancy (k) increased with DOP and was 0.12, 0.21, and 0.43 at 80, 110, and 140 DOP, respectively. There was no evidence that pregnancy affected NE, ME, NP, and MP or k and k, which were also unaffected by DOP. However, k and k increased with pregnancy progress as a response to the physiological changes that pregnant females are subjected to. PMID- 28991996 TI - Effect of trace mineral source on mineral status and performance of beef steers fed low- or high-sulfur diets. AB - A 2 * 2 factorial assessed the effect of trace mineral (TM) sources fed within low- or high-S diets on the mineral status and performance of cattle. Angus crossbred steers ( = 48; 6/pen) were blocked by BW (316 +/- 16.6 kg), assigned to low-S (0.27%; LS) or high-S (0.54%; HS; added as CaSO) diets, and supplemented TM at 10 mg Cu, 30 mg Zn, and 20 mg Mn/kg DM from hydroxy (HYD; IntelliBond; Micronutrients USA LLC, Indianapolis, IN) or inorganic (sulfates; ING) sources ( = 12 steers/treatment). Steers were fed corn silage and corn-based diets via GrowSafe bunks in the growing period (GP; 84 d) and finishing period (FP; 77 d), respectively. Plasma and liver were collected at trial initiation and end of GP and FP for mineral concentrations. End of GP and FP red blood cell lysate superoxide dismutase (SOD) and Mn-SOD activity and liver glutathione concentrations were measured. Data were used as a 2 * 2 factorial using Proc Mixed of SAS (SAS Inst. Inc., Cary, NC) with initial plasma and liver status analyzed as covariates. High S decreased ( < 0.01) liver Cu and tended ( <= 0.10) to decrease plasma Cu concentrations. Liver Cu concentrations were lower in HYD than ING in the FP ( < 0.01). High S decreased ( = 0.04) GP plasma Zn concentrations and tended to decrease ( = 0.10) GP liver Zn. There were GP ( = 0.05) and FP ( = 0.02) S * TM effects for liver Mn concentrations where GP LS-HYD was greater than all other treatments, whereas FP LS-HYD was lower than HS-HYD and LS-ING and FP HS-ING was less than LS-ING. Glutathione, SOD, and Mn-SOD were not different ( >= 0.13) in the GP, but S * TM tended to affect FP Mn-SOD ( = 0.10), where LS-HYD tended to be lower than LS-ING. Oxidized glutathione in FP tended to be lower ( = 0.06) for HYD than ING. In the GP, there were S * TM effects on performance where LS-HYD had greater ADG and G:F ( <= 0.05) than HS HYD, whereas LS and HS-ING were intermediate. For FP performance S * TM effects were noted where LS-HYD and HS-ING tended ( = 0.10) to gain more than HS-HYD and HS-HYD had lower G:F ( = 0.04) than HS-ING. There were no effects of S * TM on final BW, DMI, or ADG ( >= 0.11); however, HS-HYD had lower G:F than other treatments overall ( = 0.05). High S decreased back fat and yield grade ( = 0.03), and rib eye area was smaller for HYD than ING ( = 0.02). In this study HS decreased markers of Cu and Zn status, and differential effects of HYD vs. ING minerals were noted across dietary phases, although all steers maintained adequate TM status. PMID- 28991997 TI - Substituting ground woody plants for cottonseed hulls in lamb feedlot diets: Growth performance, blood serum chemistry, and rumen fluid parameters. AB - Effects of using ground woody plants in Rambouillet wether lamb feedlot diets on growth performance, blood serum, and rumen parameters were evaluated. A randomized design study was used with 2 feeding periods (70% concentrate diet from d 0 to 27 [Period 1] and 86% concentrate diet from d 28 to 57 [Period 2]); the concentrate portion of the diets mainly consisted of dried distiller's grains with solubles and sorghum grain. Lambs were individually fed 6 diets that differed only by roughage source ( = 8 animals/treatment; 32.9 +/- 3.2 kg initial BW): either cottonseed hulls (CSH; control) or ground wood consisting of redberry juniper (RED), blueberry juniper (BLUE), one-seeded juniper (ONE), or eastern red cedar (ERC) spp. or honey mesquite (MESQ; ). Using ground wood vs. CSH as the roughage source did not affect ( > 0.12) BW. There tended to be a treatment * day interaction ( = 0.07) for lamb DMI, attributed to Period 1 when DMI was greater ( < 0.05) for lambs fed CSH vs. RED, ONE, ERC, or MESQ during the first 14 d and greater ( < 0.05) during d 14 to 28 vs. lambs fed ERC. Overall, ADG was less for lambs fed ERC ( < 0.10) or MESQ ( < 0.05) vs. lambs fed CSH, but G:F was similar ( > 0.10) among all lambs. Dietary treatments did not affect ( > 0.15) ruminal pH, but treatment * day interactions ( < 0.05) were observed for rumen fluid ammonia N or molar proportions of propionate and butyrate; few differences were observed within day. However, overall, lambs fed RED or MESQ had greater ( < 0.05) total rumen VFA than lambs fed CSH. A treatment * day interaction ( = 0.04) was observed for the acetate:propionate ratio, but no differences ( > 0.10) were observed within day. Treatment * day interactions ( < 0.05) were observed for blood serum glucose, gamma-glutamyl transferase, the albumin:globulin ratio, total bilirubin, beta-hydroxybutyrate, P, Cl, and Mg, with most results being less for lambs fed the wood-based diets than for lambs fed the CSH diets. Results suggested that even though lamb DMI was reduced during the growing period when diets contained 30% ground woody products (RED, ONE, ERC, and MESQ), animal health and rumen fluid parameters were not negatively affected by ground woody plants. PMID- 28991998 TI - Effects of feeding ground redberry juniper (Juniperus pinchotii) to gestating ewes on pre- and postpartum performance, serum metabolites and hormones, milk fatty acid composition, and progeny preweaning performance. AB - The objective of this research was to evaluate effects of replacing sorghum * Sudangrass hay with ground juniper in gestating ewe supplements on pre- and postpartum growth performance, serum metabolites and hormonal concentrations, milk fatty acid composition, and progeny preweaning performance. In a completely randomized design, commercial Rambouillet ewes (age = 3 to 5 yr; initial BW = 65.2 +/- 1.6 kg) on a base diet of long-stem sorghum * Sudangrass hay were assigned to 1 of 4 dietary supplements in which ground juniper replaced 0% (CNTL), 33% (18JUN), 66% (36JUN), or 100% (54JUN) of the ground sorghum * Sudangrass hay in a pelleted supplement with ground juniper from d 38 +/- 4 of gestation to 2 d postpartum. Treatment DM diet intake overall (g/kg BW) in ewes receiving no juniper was similar ( >= 0.38) to that of those receiving increasing concentrations of juniper. Changes in ewe BW and BCS were similar ( >= 0.24) in ewes throughout gestation. All serum metabolites and hormones were within normal clinical ranges; however, serum IGF-1 decreased linearly ( = 0.003), alanine increased (linear; = 0.003), and serum Na decreased (linear; = 0.049) as the percentage of juniper increased in the diet. Ewe milk fatty acid composition was similar ( > 0.05) for the majority of fatty acids across treatment groups, with the exception of arachidonic acid (C20:4n6) being greater ( < 0.02) in 54JUN vs. CNTL ewe milk. Lamb birth weights were similar ( = 0.13), whereas lamb ADG tended to differ (quadratic; = 0.06) from d 0 to 14, with 18JUN being the least. At weaning, BW tended ( = 0.09) to linearly decrease in lambs born to ewes consuming greater concentrations of juniper but were not different ( = 0.26) between CNTL and 18JUN, 36JUN, and 54JUN. Results indicated that feeding increasing levels of ground juniper in supplements did not negatively alter ewe performance or serum metabolites and hormones measured pre- and postpartum. Lamb birth weight and preweaning performance appeared unaffected by maternal consumption of ground juniper containing supplements. Results also provide novel information regarding the effects of plant secondary compound consumption throughout pregnancy on ewe and progeny performance and health. PMID- 28991999 TI - Effect of combined xylanase and phytase on growth performance, apparent total tract digestibility, and carcass characteristics in growing pigs fed corn-based diets containing high-fiber coproducts. AB - Phytate has been shown to be an antinutrient, and the feeding of high levels of phytase can break down phytate to improve nutrient utilization and pig performance. Dietary xylanase targets arabinoxylan breakdown, thereby improving energy utilization in pigs. However, the effects of simultaneous supplementation have not been clearly determined. Crossbred pigs ( = 45; mean initial weight, 26.4 +/- 0.2 kg) were allotted to 1 of 9 treatments to evaluate the effects of both xylanase (endo-1,4-beta xylanase [EC 3.2.1.8]) and phytase (6-phytase [EC 3.1.3.26]) supplementation as follows: 1) positive control (PC), a corn-soybean meal-based diet with 15% corn distillers dried grains with solubles, 15% wheat middlings, and 13% corn germ meal; 2) negative control (NC), ME was reduced by 103 kcal/kg from the PC diet by replacement of fat with corn starch; 3) NC + phytase (500 phytase units (FTU)/kg diet); 4) NC + phytase (1,000 FTU/kg diet); 5) NC + phytase (2,000 FTU/kg diet); 6) NC + xylanase (24,000 xylanase units [BXU]/kg diet); 7) NC + phytase (500 FTU/kg diet) + xylanase (24,000 BXU/kg diet); 8) NC + phytase (1,000 FTU/kg diet) + xylanase (24,000 BXU/kg diet); and 9) NC + phytase (2,000 FTU/kg diet) + xylanase (24,000 BXU/kg diet). All diets were formulated to meet nutrient requirements before phytase and xylanase addition to the diets. There were no significant interactions between xylanase and phytase supplementation on growth performance, carcass characteristics, and apparent total tract digestibility (ATTD). The ADG ( < 0.01, quadratic) and G:F ( < 0.05, linear) for the overall period increased as phytase level increased. The ATTD of P increased as phytase supplementation level increased ( < 0.05, linear and quadratic). The ATTD of DM, NDF, ether extract ( < 0.05), and hemicellulose ( = 0.05) increased quadratically as phytase level increased. Estimated carcass lean percentage and lean gain increased ( < 0.05, linear) as phytase level increased. Xylanase supplementation had no effect on growth performance, ATTD, and carcass characteristics. The results demonstrated an improved nutrient digestibility, performance, and carcass response to phytase supplementation beyond P provision because all diets exceeded current P requirement estimates based on standardized total tract digestible P. PMID- 28992000 TI - Differential expression of neuregulin 1 (NRG1) and candidate miRNA regulating NRG1 transcription in the chicken oviduct in response to hormonal changes. AB - Neuregulin 1 (NRG1), a signaling protein that binds to members of the erythroblastoma (ErbB) family, is known to play essential biological roles in mediating cell-cell interactions and orchestrating vital cell functions in the heart and nervous system. NRG1 is closely associated with developmental processes in various organs and expression of several NRG1 isoforms are regulated by estrogen. However, expression and its hormonal regulation during development of the female reproductive tract remain unknown. The reproductive system of chickens undergoes dynamic morphological and functional changes in response to estrogen and the molting process. Therefore, in the current study, we found differential expression of and candidate microRNA regulating chicken transcription in response to estrogen stimulation and/or the molting process. The results revealed that relative expression of mRNA increased in the oviducts of chicks treated with diesthylstilbestrol (DES; a synthetic non-steroidal estrogen). Additionally, abundant NRG1 mRNA expression was primarily in the glandular (GE) and luminal (LE) epithelia of the magnum in the developing chick oviduct in response to exogenous estrogen. Also, expression decreased during regression of the oviduct following induced molting by feeding high levels of zinc in the diet, and then gradually resurged as the oviduct underwent remodeling and recrudescence in laying hens. In addition, the present results revealed changes in relative expression of candidate chicken microRNA (, and ) targeting transcription in chicken oviducts in response to exogenous estrogen. In conclusion, these results provide the first evidence that is a novel estrogen-responsive gene closely correlated with the estrogen-dependent development of the oviduct of chicks and regeneration of the oviduct after molting. Further, regulation of expression involving at least 3 chicken miRNA is likely a prerequisite for those estrogen regulated developmental events. PMID- 28992001 TI - Genomic inbreeding depression for climatic adaptation of tropical beef cattle. AB - Inbreeding has the potential to negatively impact animal performance. Strategies to monitor and mitigate inbreeding depression require that it can be accurately estimated. Here, we used genomewide SNP data to explore 3 alternative measures of genomic inbreeding: the diagonal elements of the genomic relationship matrix (FGRM), the proportion of homozygous SNP (FHOM), and the proportion of the genome covered by runs of homozygosity (FROH). We used 2,111 Brahman (BR) and 2,550 Tropical Composite (TC) cattle with phenotypes recorded for 10 traits of relevance to tropical adaptation. We further explored 3 marker densities ranging from a high-density chip (729,068 SNP), a medium-density chip (71,726 SNP) specifically designed for cattle, and a low-density chip (18,860 SNP) associated with the measures of inbreeding. Measures of FGRM were highly correlated across the 3 SNP densities and negatively correlated with FHOM and FROH in the BR population. In both populations, there was a strong positive correlation for each measure of inbreeding across the 3 SNP panels. We found significant ( < 0.01) inbreeding depression for various traits, particularly when using the highest density SNP chip in the BR population, where inbreeding was negatively associated with coat color and coat type such that inbred animals presented shorter, slicker, and lighter coats. Based on FGRM using the medium-density chip, we found that a 1% increase in inbreeding in the BR and TC populations was associated with a decrease of 0.514 and 0.579 kg BW, respectively, in yearlings. In the TC population, a 1% increase in FHOM was associated with a decrease in BCS of 0.636% ( < 0.001). The low-density chip, comprising SNP associated with inbreeding, captured genes, and regions with pleiotropic effects ( < 0.001). However, it did not improve our ability to identify inbreeding depression, relative to the use of higher-density panels. We conclude that where heterogeneous populations are present, such as in tropical environments where composite animals abound, measures of inbreeding that do not depend on allele frequencies, such as FHOM and FROH, are preferable for estimating genomic inbreeding. Finally, the sustainable intensification of livestock systems in tropical regions will rely on genetic safeguards to ensure that productivity is improved while also adapting animals to cope with climate change. The results of this study are a step toward achieving that goal. PMID- 28992003 TI - Rearing in captivity affects spermatogenesis and sperm quality in greater amberjack, Seriola dumerili (Risso, 1810). AB - The greater amberjack, (Risso, 1810), is a promising candidate for the diversification of European aquaculture production, but inconsistent reproduction in captivity prevents commercial production. Recent studies showed that greater amberjack confined in sea cages exhibited scarce gonad development and early interruption of gametogenic activity during the reproductive season. The aim of the present study was to improve our understanding of the observed impairment of spermatogenesis. Adult wild and captive-reared males were sampled during 3 different phases of the reproductive cycle: early gametogenesis (EARLY; late April to early May), advanced gametogenesis (ADVANCED; late May to early June), and spawning (SPAWNING; late June to July). Spermatogonial stem cells and proliferating germ cells were identified through the immunohistochemical localization of and proliferating cell nuclear antigen, respectively. Apoptotic germ cells were identified throughout the terminal deoxynucleotidyl transferase mediated 2'-deoxyuridine 5'-triphosphate nick end labeling method. Sperm quality of captive-reared fish was evaluated using computer-assisted sperm analysis. Captive-reared males exhibited seminiferous lobules of a smaller diameter, a precocious and progressive decrease of spermatogonial mitosis, and a high level of apoptosis at the beginning of the reproductive season, concomitant with a many fold higher 17beta-estradiol plasma concentration. The motile spermatozoa percentage of captive greater amberjack was lower than in other teleosts, and a drastic decrease of spermatozoa motility duration, velocity, and ATP content occurred along the reproductive season. An abnormal increase of sperm concentration as well as an increase of dead spermatozoa occurred during the SPAWNING phase, probably because of lack of sperm hydration and ejaculation and consequent sperm ageing. The present study demonstrates the extreme susceptibility of greater amberjack to rearing stress and underscores the need for improvement of the rearing and handling procedures to ameliorate gametogenesis dysfunctions in commercial aquaculture production. PMID- 28992004 TI - The effects of copper source and concentration on growth performance, carcass characteristics, and pen cleanliness in finishing pigs. AB - A total of 1,143 pigs (PIC 337 * 1050, initially 25.1 +/- 0.03 kg BW) were used in a 111-d study to determine the effects of copper sulfate (CuSO; Prince Agri Products, Quincy, IL) or tribasic copper chloride (TBCC; IntelliBond C; Micronutrients, Indianapolis, IN) on growth performance, carcass characteristics, and pen cleanliness. Pens of pigs were allotted to 1 of 6 dietary treatments, balanced on average pen weight in a randomized complete block design with 25 to 28 pigs per pen and 7 replications per treatment. Treatments included a corn soybean meal-based diet (corn-soy), a high-by-product diet with 30% distillers dried grains with solubles and 15% bakery meal (by-product diet), and the by product diet with 75 or 150 mg/kg added Cu from CuSO or TBCC. All diets contained 20 mg/kg Cu from CuSO in the trace mineral premix. At the conclusion of the trial, a digital photo of each pen was taken to allow 3 independent observers to score manure texture and buildup and to assess pen cleanliness prior to power washing. Furthermore, the time required to power wash each pen was also measured. Overall, pigs fed the by-product diet tended to have increased ADFI ( = 0.083) and had decreased G:F ( = 0.005) compared to those fed the corn-soy diet. No Cu source * level interactions or Cu source differences were observed ( > 0.05). From d 0 to 71, pigs fed increasing Cu had increased (quadratic, < 0.05) ADG, d 71 BW, and ADFI. From d 71 to 111, pigs fed increasing Cu tended to have increased ADFI (linear, = 0.068) and decreased G:F (quadratic, = 0.056). Overall (d 0 to 111), increasing Cu increased (linear, < 0.01) ADG, final BW, and ADFI (quadratic, = 0.026). Hot carcass weight increased (linear, = 0.023) by 2.4 kg with increasing Cu. Increasing Cu also increased loin depth (linear, = 0.019) and percentage lean (quadratic, = 0.024). Manure buildup and wash time (s/pen) increased ( < 0.05) for by-product diet pens compared to corn-soy pens; however, neither wash time nor pen cleanliness were influenced by added Cu. In summary, increasing dietary Cu in high-by-product diets improved growth and feed intake, resulting in increased final BW and HCW for pigs fed both Cu sources, without influencing pen wash time. PMID- 28992005 TI - Characterization of exosomes from body fluids of dairy cows. AB - Exosomes are a specific subpopulation of extracellular vesicles that are widely released by cells of different origins with divergent functions that make their way into body fluids that can be conveniently sampled. In the current study, we isolated and evaluated exosomes from concurrently collected samples of milk, plasma, saliva, and urine from a group of 6 pregnant Holstein-Friesian dairy cows (aged 7 mo, 174 to 203 d of gestation). The cows had BCS of 3.5 to 5.25 (on a scale of 1 to 10), and the milk production for the season to the time of sampling ranged between 5,118 and 6,959 kg. The low levels of extracellular vesicles in saliva and urine (more than 86% fewer compared to the extracellular vesicles in milk and plasma) precluded further detailed evaluation since utility for diagnostics was deemed unlikely. In exosomes isolated from milk and plasma, size distribution, morphology, and the presence of exosome markers was confirmed by nanoparticle tracking analysis, electron microscopy, and Western blot. In addition, a targeted proteomic approach using the quadrupole ion trap mass spectrometer was also used in the study to screen for the exosome marker (e.g., Tumor susceptibility gene 101). Following confirmation of the presence of exosomes, the proteomic profiles of milk and plasma exosomes were evaluated using information-dependent acquisition-mediated liquid chromatography-tandem mass spectrometry (LC-MS/MS). The milk exosomes contain proteins that differed greatly from the plasma exosomes, with only 8 similar proteins harbored in both the milk and plasma exosomes. The milk and plasma exosomes were found to contain proteins (e.g., immunoglobulin J chain and alpha2 macroglobulin) associated with specific biological processes and molecular functions. Hence, the fluid of origin required for exosome analysis will be dependent on the specific information needed. In conclusion, isolated exosomes from milk and plasma samples collected at the same time point from the same dairy cows encapsulated different profiles of proteins associated with different biological processes and molecular functions. PMID- 28992007 TI - Effects of diet complexity and multicarbohydrase supplementation on growth performance, nutrient digestibility, blood profile, intestinal morphology, and fecal score in newly weaned pigs. AB - To study the effects of diet complexity and multicarbohydrase (MC) supplementation, 144 piglets (6.70 +/- 0.81 kg of BW) weaned at 21 +/- 2 d of age (1:1 male to female ratio) were assigned to 1 of 6 dietary treatments in a 3 * 2 factorial arrangement based on diet complexity (complex1, complex2, and simple) and MC addition (0 vs. 0.1% of MC). Diets were provided in a 2-phase feeding program with phase I (d 1 to 14) and phase II diets (d 15 to 28). Complex1 was formulated to mimic a conventional weaner diet with blood plasma, fish meal, dried whey, and skim milk powder, whereas complex2 partially or totally replaced these ingredients with various plant-based ingredients. The simple diet primarily comprised corn, wheat, and soybean meal. No interactions were found between diet complexity and MC supplementation ( > 0.10), except for apparent total tract digestibility (ATTD) of ash and globulin concentration on d 28 ( < 0.05). Pigs fed the complex1 diet had greater ( < 0.01) ADG, ADFI, and G:F than those fed the other diets during the first week after weaning. However, no differences in ADG or ADFI were observed for pigs fed the complex1 and simple diets throughout the 28-d experimental period ( > 0.10), whereas the complex2 diet led to lower ADG and ADFI compared with the complex1 diet ( < 0.05). Overall, G:F was greater for pigs fed the simple diet compared with those fed the complex1 diet ( < 0.01). Pigs fed the simple diet showed ATTD of DM, OM, GE, and ash comparable to those fed the complex1 diet on d 14 ( > 0.10). In contrast, greater ATTD of DM, OM, NDF, GE, and ash was observed ( < 0.05) in pigs fed the complex1 diet than in those fed the complex2 diet or the simple diet on d 28. The simple diet increased the lymphocyte proportion in serum compared with the complex1 diet ( < 0.01) on d 14. Pigs fed the complex1 diet had a greater ( < 0.05) ratio of villus height (VH) to crypt depth (CD) in the ileum compared with the other diets. The complex2 diet decreased ( < 0.05) the fecal score during 3 wk of the postweaning period compared with the complex1 diet. Dietary MC supplementation increased ( < 0.05) G:F during the overall experimental period, VH in the ileum, VH:CD ratio in the duodenum, and ATTD of DM and GE but it reduced fecal score ( < 0.05). In conclusion, feeding a simple diet resulted in BW comparable to feeding the complex1 diet, but it led to inferior intestinal morphology and ATTD of nutrients on d 28. Also, MC supplementation could be beneficial regardless of diet complexity. PMID- 28992006 TI - Does microbial nitrogen contamination affect the estimation of crude protein degradability of concentrate feeds? AB - The effects of microbial contamination (MC) on CP degradability of concentrate feeds are still controversial. Therefore, the aim of this study was to use N to estimate the impact of MC on estimations of CP fractions (the soluble fraction of CP [a], the insoluble but potentially degradable fraction of CP [b], and the rate of digestion of fraction b [kd]) of concentrate feeds. Twelve types of feed were evaluated: 6 energy concentrates-wheat bran ( L.), rice meal ( L.), ground corn ( L.), ground sorghum ( Pers.), ground corn cob ( L.), and soybean hulls [ (L.) Merr.]-and 6 protein concentrates-cottonseed meal ( L.), soybean meal [ (L.) Merr.], ground bean ( L.), peanut meal ( L.), sunflower meal ( L.), and corn gluten meal ( L.). The feeds were divided into 4 groups and were incubated in the rumen of 4 crossbred bulls. The samples were incubated for 0, 2, 4, 8, 16, 24, 48, and 72 h. To estimate the MC of the incubated residues, the ruminal bacteria were labeled with N via continuous intraruminal infusion of (NH)SO. There was no difference ( = 0.738) between corrected and uncorrected parameters a, b, and kd for all feeds that were evaluated. All of the feed tests followed an exponential model of degradation, and the model fitted well to the data, except for corn gluten meal, probably because the maximum incubation time that was used (72 h) was not long enough to allow for an accurate estimation of the degradation profile. Therefore, correction of ruminal protein degradation to MC is irrelevant with regards to the concentrates that were studied. PMID- 28992008 TI - Effects of dietary l-methionine supplementation on the growth performance, carcass characteristics, meat quality, and muscular antioxidant capacity and myogenic gene expression in low birth weight pigs. AB - The aim of the present study was to investigate the effects of dietary Met supplementation on the growth performance, carcass characteristics, meat quality, and muscular antioxidant capacity and myogenic gene expression in low birth weight (LBW) pigs. Thirty normal birth weight (NBW) and 60 LBW female piglets were selected at birth. In each litter, after weaning, 1 of the LBW piglets (LBW CON group) and 1 of the NBW piglets (NBW-CON group) were fed the basal diets and 1 LBW littermate was fed the basal diet supplemented with Met (LBW-MET group). Thus, all pigs were distributed into groups of 3 treatments * 6 replicates (pens) * 5 piglets per replicate up to 180 d of age. Compared with NBW-CON pigs, LBW-CON pigs had decreased ADG ( = 0.004) and ADFI ( < 0.001) during the postweaning period and greater backfat thickness ( = 0.015) at slaughter. In addition, LBW CON pigs exhibited compromised meat quality, as evidenced by a greater drip loss at 24 h postmortem( = 0.037) and a lower pH at 45 min postmortem ntents of malondialdehyde (MDA; = 0.046) and protein carbonyl ( = 0.028) in the LM. The LBW pigs fed the Met-supplemented diets had a greater amount of reduced glutathione (GSH; = 0.009) but a lower level of MDA ( = 0.015) in the LM compared with the LBW-CON pigs. Methionine supplementation increased the pH at 24 h postmortem (pH) value ( = 0.004) but reduced the drip loss at both 24 ( = 0.016) and 48 h ( = 0.005) postmortem of LBW-MET pigs in comparison with the LBW-CON pigs. The Met supplemented diets increased the -adenosyl-methionine content ( = 0.006), DNA methyltransferase activity ( = 0.007), and CpG methylation levels of the sites +27 ( = 0.008) and +160 ( = 0.009) of myostatin (MSTN) exon 1 but decreased the mRNA expression of MSTN ( = 0.011) in the LM of the LBW-MET group compared with the LM of the LBW-CON group. Additionally, when compared with the LBW-CON group, the area of LM ( = 0.037) was significantly increased in the LBW-MET group, in parallel with the upregulated mRNA abundance of myogenin ( = 0.025), myocyte enhancer factor 2A ( = 0.036), and myocyte enhancer factor 2D ( = 0.015). In conclusion, Met supplementation increases pH and decreases drip loss in the LM of LBW-MET pigs, along with a greater GSH content but a lower MDA accumulation. Also, the LBW-MET pigs showed a greater LM area, which may be associated with the improved expression of myogenic genes. PMID- 28992009 TI - Technical note: Relationship between in situ NDF degradability and enzymatic NDF hydrolysis in forages, nonforage fibrous feeds, and crop residues. AB - The study was performed on forages ( = 8), nonforage fibrous feeds ( = 10), and crop residues ( = 2). Samples were characterized for in situ NDF degradability (NDFD) at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, and 240 h of ruminal incubation. Then, samples were characterized for enzymatic NDFD by adopting a multistep enzymatic method consisting of a preincubation (PreInc) phase followed by enzymatic incubation (EnzInc) steps. In the PreInc phase, samples were incubated in a NaOH solution for 0, 30, 60, or 90 min. Then, in the EnzInc phase, samples were first incubated in a buffered enzymatic solution containing hemicellulase, cellulase, and Viscozyme L enzymes. Then, samples were incubated in a xylanase-buffered enzymatic solution. These 2-step EnzInc lasted for a total of 16 (8 h for the first enzymatic step + 8 h for the second enzymatic step), 32 (16 + 16 h), or 48 h (24 + 24 h). The enzymatic NDFD coefficients were increased by increasing both PreInc and EnzInc incubation times, and no PreInc * EnzInc interaction was observed, except for ryegrass hay. On average, enzymatic NDFD increased ( < 0.05) by 0.35, 0.54, or 0.68, respectively, for 30-, 60-, or 90-min PreInc compared with 0-min PreInc. The enzymatic NDFD increased ( < 0.05), on average, by 0.11 in 32-h EnzInc or 0.16 in 48-h EnzInc with respect to 16-h EnzInc. Enzymatic NDFD were used to predict in situ NDFD coefficients by adopting single regression equations. High coefficients of regression ( > 0.80, < 0.05) and low errors of prediction were measured when specific enzymatic conditions were performed to predict in situ NDFD at intermediate (from 24 to 48 h) ruminal incubation. Generally, worse regression performances were obtained when enzymatic NDFD were used to predict in situ NDFD evaluated after shorter or longer incubation times. The direct prediction of the rate of NDF degradation was not possible using enzymatic NDFD coefficients. Even if the proposed multistep enzymatic method appeared promising, further studies are required to improve enzymatic NDFD prediction ability within specific forage types or nonforage fibrous feeds. PMID- 28992010 TI - Genotype by environment interaction effects in genetic evaluation of preweaning gain for Line 1 Hereford cattle from Miles City, Montana. AB - It has long been recognized that genotype * environment interaction potentially influences genetic evaluation of beef cattle. However, this recognition has largely been ignored in systems for national cattle evaluation. The objective of this investigation was to determine if direct and maternal genetic effects on preweaning gain would be reranked depending on an environmental gradient as determined by year effects. Data used were from the 76-yr selection experiment with the Line 1 Hereford cattle raised at Miles City, MT. The data comprised recorded phenotypes from 7,566 animals and an additional 1,862 ancestral records included in the pedigree. The presence of genotype * environment interaction was examined using reaction norms wherein year effects on preweaning gain were hypothesized to linearly influence the EBV. Estimates of heritability for direct and maternal effects, given the average environment, were 10 +/- 2 and 26 +/- 3%, respectively. In an environment that is characterized by the 5th (95th) percentile of the distribution of year effects, the corresponding estimates of heritability were 18 +/- 3 (22 +/- 3%) and 30 +/- 3% (30 +/- 3%), respectively. Rank correlations of direct and maternal EBV appropriate to the 5th and 95th percentiles of the year effects were 0.67 and 0.92, respectively. In the average environment, the genetic trends were 255 +/- 1 g/yr for direct effects and 557 +/ 3 g/yr for maternal effects. In the fifth percentile environment, the corresponding estimates of genetic trend were 271 +/- 1 and 540 +/- 3 g/yr, respectively, and in the 95th percentile environment, they were 236 +/- 1 and 578 +/- 3 g/yr, respectively. Linear genetic trends in environmental sensitivity were observed for both the direct (-8.06 * 10 +/- 0.49 * 10) and maternal (8.72 * 10 +/- 0.43 * 10) effects. Therefore, changing systems of national cattle evaluation to more fully account for potential genotype * environment interaction would improve the assessment of breeding stock, particularly for direct effects. Estimates of environmental sensitivity parameters could also facilitate identification of genetic limitations to production. PMID- 28992011 TI - Is shade for horses a comfort resource or a minimum requirement? AB - Shade or shelter as protection from extremes of weather is required for horses at agricultural research and teaching facilities and is recommended or required by many states, professional organizations, and industry groups. The focus of this paper is the recent research on the responses of horses to hot, sunny weather, which has begun to provide scientific evidence that characterizes how and when shade is used and any benefits shade confers on horses. These behavioral and physiological findings support provision of shade as a resource for thermal comfort and the expression of normal behavior that should be included as a standard of best care practices for healthy adult horses living in the environmental conditions reviewed, rather than an absolute minimum care requirement. Additional research is required for horses living under other environmental conditions, for very young or old horses, horses in very poor body condition, or those with compromised health to determine if their responses to hot, sunny weather differ from those presented here. PMID- 28992012 TI - Rapid Communication: Evaluation of methane inhibitor 3-nitrooxypropanol and monensin in a high-grain diet using the rumen simulation technique (Rusitec). AB - The objective of this study was to evaluate the effects of 3-nitrooxypropanol (NOP), a known methane (CH) inhibitor; the ionophore monensin (MON); and their combination on in vitro CH production in a high-grain diet (85% barley grain, 10% barley silage, and 5% vitamin-mineral supplement; DM basis) using a rumen simulation technique (Rusitec). Sixteen fermentation vessels in 2 Rusitec apparatuses (blocks) were used in a completely randomized block design with 4 treatments: Control, NOP (200 ug/g DM), MON (200 ug/g DM), and the combination of 200 ug NOP/g DM and 200 ug MON/g DM (NOP + MON). Two fermenters within each apparatus were randomly assigned to a treatment. Treatments were mixed with 10 g of substrate and supplied on a daily basis. The study included an 8-d adaptation period without treatment supplementation and a 6-d period for addition of treatments. Dry matter disappearance, pH, and total VFA were not affected by treatment ( >= 0.34). Acetate proportion was decreased by 8.3% and 14.9% with NOP and NOP + MON ( < 0.01), respectively; however, propionate proportion was not affected by treatment ( = 0.44). The acetate to propionate ratio was lowered by 21.1% with the combination of NOP and MON ( = 0.02), whereas ammonia-N concentration was not affected by treatment ( = 0.50). Total gas production was unaffected ( = 0.50), but CH production decreased by 77.7% and 75.95% ( < 0.01) with NOP and NOP + MON addition, respectively. Concurrently, H gas production increased by 131.3% and 185.6% ( = 0.01) with NOP and NOP + MON treatments, respectively. The copy number of methanogens was decreased in both solid and liquid phases ( < 0.01) with NOP and NOP + MON treatments. Despite the combination of NOP + MON showing the greatest decrease in acetate molar proportion and acetate to propionate ratio, it did not further inhibit CH beyond the effect of NOP alone. The decrease in CH emissions with treatments that included NOP occurred along with a decrease in the copy number of methanogens associated with the solid and liquid phases, confirming the inhibitory effects of NOP on these microorganisms. In conclusion, the combined effects of NOP and MON on CH mitigation did not exceed the effect of NOP alone when using a high-grain diet in vitro. PMID- 28992014 TI - The digestible energy, metabolizable energy, and net energy content of dietary fat sources in thirteen- and fifty-kilogram pigs. AB - The objective was to determine the energy concentration of a diverse array of dietary fat sources and, from these data, develop regression equations that explain differences based on chemical composition. A total of 120 Genetiporc 6.0 * Genetiporc F25 (PIC, Inc., Hendersonville, TN) individually housed barrows were studied for 56 d. These barrows (initial BW of 9.9 +/- 0.6 kg) were randomly allotted to 1 of 15 dietary treatments. Each experimental diet included 95% of a corn-soybean meal basal diet plus 5% either corn starch or 1 of 14 dietary fat sources. The 14 dietary fat sources (animal-vegetable blend, canola oil, choice white grease source A, choice white grease source B, coconut oil, corn oil source A, corn oil source B, fish oil, flaxseed oil, palm oil, poultry fat, soybean oil source A, soybean oil source B, and tallow) were selected to provide a diverse and robust range of unsaturated fatty acid:SFA ratios (U:S). Pigs were limit-fed experimental diets from d 0 to 10 and from d 46 to 56, providing a 7-d adaption for fecal collection on d 7 to 10 (13 kg BW) and d 53 to 56 (50 kg BW). At 13 kg BW, the average energy content of the 14 sources was 8.42 Mcal DE/kg, 8.26 Mcal ME/kg, and 7.27 Mcal NE/kg. At 50 kg BW, the average energy content was 8.45 Mcal DE/kg, 8.28 Mcal ME/kg, and 7.29 Mcal NE/kg. At 13 kg BW, the variation of dietary fat DE content was explained by DE (Mcal/kg) = 9.363 + [0.097 * (FFA, %)] - [0.016 * omega-6:omega-3 fatty acids ratio] - [1.240 * (arachidic acid, %)] - [5.054 * (insoluble impurities, %)] + [0.014 * (palmitic acid, %)] ( = 0.008, = 0.82). At 50 kg BW, the variation of dietary fat DE content was explained by DE (Mcal/kg) = 8.357 + [0.189 * U:S] - [0.195 * (FFA, %)] - [6.768 * (behenic acid, %)] + [0.024 * (PUFA, %)] ( = 0.002, = 0.81). In summary, the chemical composition of dietary fat explained a large degree of the variation observed in the energy content of dietary fat sources at both 13 and 50 kg BW. PMID- 28992015 TI - More feed efficient sheep produce less methane and carbon dioxide when eating high-quality pellets. AB - The Australian sheep industry aims to increase the efficiency of sheep production by decreasing the amount of feed eaten by sheep. Also, feed intake is related to methane production, and more efficient (low residual feed intake) animals eat less than expected. So we tested the hypothesis that more efficient sheep produce less methane by investigating the genetic correlations between feed intake, residual feed intake, methane, carbon dioxide, and oxygen. Feed intake, methane, oxygen, and carbon dioxide were measured on Merino ewes at postweaning (1,866 at 223 d old), hogget (1,010 sheep at 607 d old), and adult ages (444 sheep at 1,080 d old). Sheep were fed a high-energy grower pellet ad libitum for 35 d. Individual feed intake was measured using automated feeders. Methane was measured using portable accumulation chambers up to 3 times during this feed intake period. Heritabilities and phenotypic and genotypic correlations between traits were estimated using ASReml. Oxygen (range 0.10 to 0.20) and carbon dioxide (range 0.08 to 0.28) were generally more heritable than methane (range 0.11 to 0.14). Selecting to decrease feed intake or residual feed intake will decrease methane (genetic correlation [] range 0.76 to 0.90) and carbon dioxide ( range 0.65 to 0.96). Selecting to decrease intake ( range 0.64 to 0.78) and methane ( range 0.81 to 0.86) in sheep at postweaning age would also decrease intake and methane in hoggets and adults. Furthermore, selecting for lower residual feed intake ( = 0.75) and carbon dioxide ( = 0.90) in hoggets would also decrease these traits in adults. Similarly, selecting for higher oxygen ( = 0.69) in hoggets would also increase this trait in adults. Given these results, the hypothesis that making sheep more feed efficient will decrease their methane production can be accepted. In addition, carbon dioxide is a good indicator trait for feed intake because it has the highest heritability of the gas traits measured; is cheaper, faster, and easier to measure than feed intake and has strong phenotypic and genetic correlations with feed intake. Furthermore, selection for feed intake, feed efficiency, methane, and carbon dioxide can be done early in sheep at postweaning age or hoggets. This early selection reduces the generation interval for breeding, thereby increasing response to selection. PMID- 28992016 TI - Determining the effects of early gestation in utero heat stress on postnatal fasting heat production and circulating biomarkers associated with metabolism in growing pigs. AB - The study objective was to characterize effects of early gestation in utero heat stress (IUHS) on postnatal fasting heat production (FHP) and blood biomarkers associated with metabolism in growing pigs. Based on previous observation of increased postnatal core body temperature set point in IUHS pigs, we hypothesized that FHP would be altered during postnatal life because of IUHS. Pregnant first parity gilts were exposed to thermoneutral (TN; = 4; 17.8 +/- 0.1 degrees C) or heat stress (HS; = 4; cyclical 28 to 38 degrees C) conditions from d 30 to 60 of gestation. At weaning (21 d of age), 2 median-weight male pigs (1 barrow and 1 boar) were selected from each litter ( = 8 in utero TN [IUTN] and 8 IUHS pigs) and then housed in TN conditions based on age. Blood samples were collected at 8, 9, and 10 wk of age when pigs were in a fed state to analyze thyroxine (T4) and triiodothyronine (T3) concentrations. Pigs were trained to enter an indirect calorimeter from wk 8 through 10 of life and then acclimated over a 24-h period 1 wk prior to testing. At 12 wk of age, pigs were fasted for 24 h, and then indirect calorimetry was performed on individual pigs over a 23-h testing period to determine FHP and the respiratory quotient in 3 intervals (0900 to 1700 h, 1700 to 0000 h, and 0000 to 0800 h). Body weight was determined before and after testing and was similar for all pigs ( = 0.77; 37.0 +/- 0.5 kg BW). Data were analyzed using PROC MIXED in SAS 9.4. No boar vs. barrow differences were observed with any analysis. Overall, FHP per kilogram BW was greater ( = 0.03; 12.1%) in IUHS pigs compared with IUTN pigs. Fasting heat production per kilogram BW was greater ( < 0.01; 19.8%) from 0900 to 1700 h compared with 1700 to 0000 h and 0000 to 0800 h and was greater (10.9%) from 1700 to 0000 h compared with 0000 to 0800 h. The RQ did not differ by in utero treatment ( = 0.51; 0.72 +/- 0.01); however, the RQ was increased ( < 0.01; 13.0%) from 1700 to 0000 h compared with 0900 to 1700 h and 0000 to 0800 h. No other FHP and RQ differences were detected. Although no in utero treatment differences were observed for T4 ( = 0.11; 52.2 +/ 6.2 ng/mL), T3 was greater overall ( = 0.04; 19.5%) in IUHS pigs than in IUTN pigs. In summary, FHP and circulating T3 were increased in IUHS pigs, and this may have implications for postnatal production efficiency in pigs gestated during hot summer months. PMID- 28992017 TI - Digestible, metabolizable, and net energy of camelina cake fed to growing pigs and additivity of energy in mixed diets. AB - This experiment was conducted to determine the DE, ME, and NE contents of camelina cake (CC) and to test the hypothesis that dietary glucosinolates originating from CC will affect the additivity of energy in mixed diets containing different inclusion levels of corn, soybean meal (SBM), and CC. A total of 30 growing barrows ([Yorkshire * Landrace] * Duroc) with a mean BW of 16.8 kg (SD 1.4) were randomly allotted to 1 of 5 treatments with 6 replicates per treatment. Pigs were fed experimental diets for 16 d, including 10 d for adaptation and 6 d for total collection of feces and urine. The 5 experimental diets consisted of 3 corn-based diets to determine the DE, ME, and NE of the 3 ingredients (corn, SBM, and CC) and 2 mixed diets to test the additivity of DE, ME, and NE. The corn diet contained 97.52% corn; the SBM diet contained 67.52% corn and 30.0% SBM; the CC diet contained 67.52% corn and 30.0% CC; the Mixed diet 1 contained 67.52% corn, 20.0% SBM, and 10.0% CC; and the Mixed diet 2 contained 67.25% corn, 10.0% SBM, and 20.0% CC. Vitamins and minerals were included in the diets to meet or exceed the requirements for growing pigs (). Pigs were fed their assigned diets at 550 kcal ME/kg BW per day on the basis of BW on d 1, 5, and 10, which was close to ad libitum intake. Pigs had free access to water. Determined DE, ME, and NE contents of corn were 3,348, 3,254, and 2,579 kcal/kg, respectively; those of SBM were 3,626, 3,405, and 2,129 kcal/kg, respectively; and those of CC were 3,755, 3,465, and 2,383 kcal/kg, respectively. No differences between the predicted and determined DE, ME, and NE were observed in the 2 mixed diets. In conclusion, DE, ME, and calculated NE content of CC fed to growing pigs were 3,755, 3,465, and 2,383 kcal/kg (as-fed basis), respectively. In addition, additivity of DE, ME, and calculated NE was observed in the mixed diets containing corn, SBM, and CC, which indicates that dietary glucosinolates originating from up to 30% of CC inclusion do not affect DE, ME, and calculated NE of diets. PMID- 28992018 TI - Technical Note: Evaluation of individual ultraviolet radiation dosimeter sensitivity and specificity for assessing shade use. AB - The effects of solar or UV radiation on livestock are often evaluated in research focused on heat stress, dermatological conditions, and other topics, with radiation measurements recorded by instrumentation at a field or local weather station for a general geographical location. Individual sensors would be valuable for quantifying an individual animal's exposure, especially as they move about in a heterogeneous environment. Individual commercially available UV dosimeters were evaluated for specificity and sensitivity and found to be potentially valuable research tools for assessing and comparing the UV radiation exposure of individual animals. PMID- 28992019 TI - Composition of the microbiota in forestomach fluids and feces of Japanese Black calves with white scours. AB - The objective of this study was to characterize the composition of the forestomach and fecal microbiota in Japanese Black calves with white scours. Forestomach fluid, feces, and peripheral blood were collected from healthy calves ( = 5; age 10 +/- 2 d) and scouring calves ( = 5; age 10 +/- 1 d) on the day on which white scours occurred. The pH and concentrations of VFA, lactic acid, and ammonia nitrogen (NH-N) of the forestomach fluids were determined. Microbiota composition and gene copy numbers in the forestomach fluid and feces were analyzed by 454 pyrosequencing and quantitative real-time PCR (qPCR), respectively. The cytokine mRNA level in peripheral leukocytes was evaluated by qPCR. The pH of the forestomach fluid of the scouring calves tended to be higher than that of the healthy calves ( = 0.056). No significant difference was detected in the total VFA, lactic acid, or NH-N concentrations in the forestomach fluids of the 2 groups. Firmicutes, Bacteroidetes, and Proteobacteria were the predominant phyla in the forestomach fluid and feces. At the genus level, the relative abundance of in the forestomach fluid was significantly higher in the scouring calves ( < 0.05) and the relative abundance of in the feces was significantly higher than that in the forestomach in the healthy calves ( < 0.05). Furthermore, the bacterial diversity indices of feces were lower in the scouring calves. Quantitative PCR amplification using some of the primer pairs failed in the forestomach fluid and feces in both groups. These results suggested that fermentation in the forestomach may affect the occurrence of white scours, resulting in changes in the composition and diversity of the forestomach fluid and fecal microbiota in Japanese Black calves. PMID- 28992020 TI - Rapid Communication: Dietary selenium improves skeletal muscle mitochondrial biogenesis in young equine athletes. AB - Exercise is known to promote mitochondrial biogenesis in skeletal muscle as well as enhance mitochondrial function and efficiency in human and rodent models. These adaptations help to decrease exercise-associated production of reactive oxygen species, which can negatively affect health and performance if antioxidant mechanisms are overwhelmed. Little is known about the adaptations of mitochondria in response to exercise training in the growing horse or if supplementation with a dietary antioxidant can improve mitochondrial function. To evaluate the separate and combined effects of selenium (Se) supplementation, training, and an acute strenuous exercise bout on mitochondrial adaptations in young horses, 30 American Quarter Horse yearlings were randomly assigned to an exercise training group or a no-training group and, within each group, received either 0.1 or 0.3 mg Se/kg DM for 14 wk. The study was split into 2 phases (wk 0 to 8 and wk 9 to 14), with half of the trained horses switched to the opposite dietary treatment in Phase 2. At the end of each phase, all horses underwent a 120-min submaximal exercise test (SET; SET 1 and SET 2). Biopsies of the middle gluteal muscle were collected before and after each phase of the study and in response to each SET and analyzed for markers of mitochondrial number and function. At rest, horses receiving 0.3 mg Se/kg DM had higher citrate synthase activity ( = 0.021) than horses receiving 0.1 mg Se/kg DM, indicating higher mitochondrial content. In contrast, cytochrome oxidase (CCO) activity was not affected by dietary Se overall, but horses that were dropped from 0.3 mg Se/kg DM to 0.1 mg Se/kg DM during Phase 2 showed a decrease ( = 0.034) in integrated CCO activity from wk 9 to 14, suggesting impaired mitochondrial function. Mitochondrial enzyme activities were unaffected by an acute, strenuous exercise bout (SET 1 and SET 2). Our relatively low-intensity exercise training protocol did not appear to induce functional mitochondrial adaptations. However, elevated dietary Se may impart beneficial effects on mitochondrial biogenesis during growth and training. A more strenuous exercise training protocol should be investigated to determine the potential benefits of elevated dietary Se for elite equine athletes. PMID- 28992021 TI - Evaluation of Rambouillet, Polypay, and Romanov-White Dorper * Rambouillet ewes mated to terminal sires in an extensive rangeland production system: Lamb production. AB - Ewe productivity (i.e., total number or weight of lambs weaned per breeding ewe) is a key indicator of lamb production efficiency. This study compared various measures of ewe productivity and ewe and lamb performance among ewes of 3 breed types mated to rams of 4 terminal-sire breed types in an extensive rangeland production system. Purebred Rambouillet ( = 212), purebred Polypay ( = 236), and crossbred Romanov-White Dorper * Rambouillet (RW-RA; = 231) ewes were produced from locally adapted Polypay and Rambouillet ewes and then annually mated to Columbia, Suffolk, Columbia * Suffolk, or Suffolk * Columbia sires for up to 4 yr, beginning at 1 yr of age. The cumulative number and weight of lambs weaned through 4 yr were greater for RW-RA (5.9 lambs and 153 kg, respectively) and Polypay ewes (4.9 lambs and 123 kg, respectively) than for Rambouillet ewes (2.9 lambs and 99 kg, respectively) and also were greater for RW-RA ewes than for Polypay ewes (all < 0.001). Greater productivity of RW-RA and Polypay ewes, compared with Rambouillet ewes, was driven by greater lambing rates (ewes lambing per ewe exposed) as ewe lambs (87 and 77 vs. 31%, respectively; < 0.001) and greater ( < 0.001) litter sizes as ewe lambs (1.3, 1.3, and 1.0, respectively) and adult ewes (2.1, 2.0, and 1.6, respectively). The RW-RA ewes also had greater longevity ( < 0.01) and cumulative lambing rates ( < 0.001) than Polypay and Rambouillet ewes. Lamb BW at birth and weaning in adult ewes favored less prolific Rambouillet ewes ( < 0.001), but after adjustment for type of birth and rearing and weaning age, differences in weaning BW among ewe breed types were small and not significant ( = 0.08). Effects of sire breed type on measures of cumulative ewe productivity were not significant ( > 0.74), but Suffolk-sired lambs had the heaviest adjusted birth weights ( = 0.01) and Columbia-sired lambs tended to have the lightest adjusted weaning weights ( = 0.12). Combined effects of heterosis and additive breed effects were associated with greater lambing rates in ewe lambs, larger litters at all ages, and substantially greater number and weight of lambs weaned for Polypay and RW-RA ewes than for Rambouillet ewes. PMID- 28992022 TI - Fiber digestion kinetics and protein degradability characteristics of stockpiled Tifton 85 bermudagrass. AB - A 2-yr study was conducted to determine effects of N fertilization level on fiber digestion kinetics and protein degradability characteristics of stockpiled Tifton 85 bermudagrass (T85). Six 0.76-ha pastures of stockpiled T85 were cut to a 10-cm stubble height on August 1 of each yr and fertilized with 56 (56N), 112 (112N), or 168 (168N) kg N/ha (2 pastures/treatment). Fiber digestion kinetics included the 72-hr potential extent of NDF digestion (PED), rate of NDF digestion, and lag time. In yr 1 and 2, PED decreased over the stockpile season. Rates of NDF digestion did not differ ( > 0.05) among N fertilization treatments in either yr. In yr 1, rate of NDF digestion was greatest ( < 0.05) in October/November, and decreased beginning in December. In yr 2, rate of NDF digestion decreased ( < 0.05) in January compared with November, but digestion rates were similar for November and January 21 sampling dates. Lag time was greater ( < 0.05) for the 112N than 56N and 168N treatments, and increased ( < 0.05) across sampling dates in yr 1. In yr 2, lag time increased ( < 0.05) from 9.0 to 17.7 h across the season. In yr 1 and 2, a negative correlation ( < 0.05) between forage lignin concentration and both PED ( = -0.91 and -0.87 in yr 1 and 2, respectively) and rate of NDF digestion ( = -0.60 and -0.25 in yr 1 and 2, respectively) was observed. There was a trend ( = 0.06) for lignin concentration to be positively correlated with lag time ( = 0.39) in yr 1, and a strong relationship was observed in yr 2 ( = 0.91; < 0.05). The RDP fraction as a % of CP was >= 90% throughout both years. Concentration of RDP (% of total DM) decreased across the stockpiling season through January in yr 1 and 2. Results suggest that kinetic parameters of NDF digestion in stockpiled T85 were influenced more by temporal changes over the stockpile season than by N fertilization level. Supplement formulations based on kinetic parameters of fiber digestion may require periodic adjustment to insure that energy-yielding components of NDF are sufficient to meet animal requirements throughout the stockpile season. The CP fraction in stockpiled T85 contains sufficient RDP to support fibrolytic activity and growth of ruminal microorganisms throughout the stockpile season. Toward the latter end of the season, supplementation with sources of digestible fiber and RDP could be expected to increase MP supply to the host animal. PMID- 28992023 TI - Garlic diallyl disulfide and diallyl trisulfide mitigates effects of pro-oxidant induced cellular stress and has immune modulatory function in LPS-stimulated porcine epithelial cells. AB - The objective of the current study was to determine if garlic-derived diallyl disulfide (DADS) and diallyl trisulfide (DATS) could mitigate oxidative and endotoxin stress, using an intestinal porcine epithelial cell (IPEC-J2) model. The experiment was arranged as a 2 * 2 * 2 factorial of DADS + DATS (0 or 18 uM), pro-oxidant stressor (hydrogen peroxide at 0 or 100 uM), and endotoxin stressor (lipopolysaccharide [LPS] at 0 or 10 ug/mL) with 8 replicates per treatment. Cells were incubated with DADS + DATS for 18 h, LPS for 6 h, then with hydrogen peroxide for 3 h. Gene expression was measured by RT-PCR for cytokines, interleukin 8 (IL-8) and tumor necrosis factor alpha (TNF-alpha), and tight junction proteins, claudin 1 (CL-1), occludin (OC), and zonula occludens 1 (ZO 1). Trans-epithelial electrical resistance (TEER), the antioxidant enzyme catalase, and apical secretion of IL-8 protein into the incubation medium was also measured. There was an increase ( < 0.01) in TNF-alpha and IL-8 gene expression due to LPS, although there was no effect of hydrogen peroxide or DADS + DATS. Furthermore, there was a tendency for an increase ( = 0.08) in ZO-1 gene expression due to DADS + DATS. Treatment with DADS + DATS and hydrogen peroxide did not affect TEER, although there was a decrease ( = 0.02) in TEER with LPS incubation. Treatment of cells with hydrogen peroxide reduced catalase activity ( < 0.01), which was restored with pre-incubation of DADS + DATS ( < 0.10). There was an increase ( < 0.01) in IL-8 secretion due to LPS, which was further augmented ( < 0.01) by pre-incubation with DADS + DATS. Based on the results from the current study, DADS + DATS can ameliorate oxidative effects of hydrogen peroxide, as well as alter IL-8 secretion in LPS-treated IPEC-J2 cells. PMID- 28992025 TI - Temporal proteomic response to acute heat stress in the porcine muscle sarcoplasm. AB - Heat stress (HS) is an important topic in the swine industry, costing hundreds of millions of dollars in economic losses annually, figures that could easily rise in light of global climate change. Muscle biology during HS is particularly important given skeletal muscle's large proportion to the body and its ultimate conversion to meat. Here we report the proteomic changes that occur during acute HS (37 degrees C and 40% relative humidity) lasting 2, 4, or 6 h in the muscle sarcoplasm of growing pigs in comparison with 6 h of thermal neutral (TN; 21 degrees C and 70% relative humidity) conditions ( = 8 per treatment). The red and white areas of the semitendinosus muscle were used to compare the differential effects of HS on oxidative or glycolytic muscles. The results support the hypothesis of proteomic profile differences between the acute HS and TN groups. Altered abundance ( < 0.05) of several proteins occurred in as little as 2 h of HS, affecting metabolism, cell structure, and chaperone, antioxidant, and proteolytic activity. We determined that the muscle HS response is both fiber type and time specific. Overall, more differences were observed in the red semitendinosus than in the white semitendinosus, although the time point at which differences were observed varied. These data show that as little as 2 h of HS has measurable effects on muscle proteins, indicating that acute HS has the potential to impair muscle function and growth. PMID- 28992027 TI - GENOMICS SYMPOSIUM: Translational genomics to improve fertility of animals. PMID- 28992026 TI - Amino acid and phosphorus digestibility of fermented corn-soybean meal mixed feed with Bacillus subtilis and Enterococcus faecium fed to pigs. AB - In the present study, a 2-stage solid-state fermentation process using followed by was performed with the purpose of improving the nutritional quality of corn and soybean meal (SBM) mixed feed (MF). The matrix of native MF and fermented MF (FMF) was analyzed using scanning electron microscopy to determine external structures after solid-state fermentation. Results of the present study indicated that the FMF had a greater concentration of CP and total P compared with the unfermented feed, whereas the contents of beta-conglycinin, glycinin, phytate P, raffinose, stachyose, and NDF in FMF declined by 77.6, 86.7, 41.2, 47.2, 36.6, and 38.9%, respectively. The content of trichloroacetic acid-soluble protein, particularly those of small peptides and free AA, increased more than 3 times after fermentation. Scanning electron microscopy revealed that irregular shapes and a lot of porous structures were observed in the SBM of FMF, the cell wall of corn in FMF was destroyed, and the number of starch granules was decreased after 2-stage fermentation. Two animal experiments were conducted to evaluate the digestibility of CP and P in FMF when fed to pigs. In Exp. 1, 6 barrows (15.20 +/ 1.27 kg initial BW) fitted with a T-cannula in the distal ileum were allotted to a replicated 3 * 3 Latin square with 3 diets and 3 periods per square. Two diets containing unfermented MF or FMF as the only source of protein and a N-free diet were formulated. Results indicated that the apparent ileal digestibility (AID) of total AA and Lys in FMF (74.98 and 75.34%) were greater ( < 0.05) than in untreated MF (69.66 and 68.56%). The standard ileal digestibility (SID) of Lys in FMF (82.17%) was also greater ( < 0.05) than in MF (75.91%). In Exp. 2, 16 barrows (17.57 +/- 1.08 kg initial BW) were allotted to 2 diets formulated to contain MF or FMF as the sole source of P to determine the digestibility of P. The apparent total tract digestibility and standardized total tract digestibility of P in FMF were 58.14 and 64.72%, respectively. These values were greater ( < 0.01) than in untreated MF (37.11 and 44.89%, respectively). Our results indicate that a solid-state fermentation process using followed by offers an effective approach to improving the quality of corn and SBM MF. PMID- 28992028 TI - GENOMICS SYMPOSIUM: Using genomic approaches to uncover sources of variation in age at puberty and reproductive longevity in sows. AB - Genetic variants associated with traits such as age at puberty and litter size could provide insight into the underlying genetic sources of variation impacting sow reproductive longevity and productivity. Genomewide characterization and gene expression profiling were used using gilts from the University of Nebraska Lincoln swine resource population ( = 1,644) to identify genetic variants associated with age at puberty and litter size traits. From all reproductive traits studied, the largest fraction of phenotypic variation explained by the Porcine SNP60 BeadArray was for age at puberty (27.3%). In an evaluation data set, the predictive ability of all SNP from high-ranked 1-Mb windows (1 to 50%), based on genetic variance explained in training, was greater (12.3 to 36.8%) compared with the most informative SNP from these windows (6.5 to 23.7%). In the integrated data set ( = 1,644), the top 1% of the 1-Mb windows explained 6.7% of the genetic variation of age at puberty. One of the high-ranked windows detected (SSC2, 12-12.9 Mb) showed pleiotropic features, affecting both age at puberty and litter size traits. The RNA sequencing of the hypothalami arcuate nucleus uncovered 17 differentially expressed genes (adjusted < 0.05) between gilts that became pubertal early (<155 d of age) and late (>180 d of age). Twelve of the differentially expressed genes are upregulated in the late pubertal gilts. One of these genes is involved in energy homeostasis (), a function in which the arcuate nucleus plays an important contribution, linking nutrition with reproductive development. Energy restriction during the gilt development period delayed age at puberty by 7 d but increased the probability of a sow to produce up to 3 parities ( < 0.05). Identification of pleotropic functional polymorphisms may improve accuracy of genomic prediction while facilitating a reduction in sow replacement rates and addressing welfare concerns. PMID- 28992029 TI - Genetic co-variance functions for live weight, feed intake, and efficiency measures in growing pigs. AB - The objective of the present study was to estimate genetic co-variance parameters pertaining to live weight, feed intake, and 2 efficiency traits (i.e., residual feed intake and residual daily gain) in a population of pigs over a defined growing phase using Legendre polynomial equations. The data set used consisted of 51,893 live weight records and 903,436 feed intake, residual feed intake (defined as the difference between an animal's actual feed intake and its expected feed intake), and residual daily gain (defined as the difference between an animal's actual growth rate and its expected growth rate) records from 10,201 growing pigs. Genetic co-variance parameters for all traits were estimated using random regression Legendre polynomials. Daily heritability estimates for live weight ranged from 0.25 +/- 0.04 (d 73) to 0.50 +/- 0.03 (d 122). Low to moderate heritability estimates were evident for feed intake, ranging from 0.07 +/- 0.03 (d 66) to 0.25 +/- 0.02 (d 170). The estimated heritability for residual feed intake was generally lower than those of both live weight and feed intake and ranged from 0.04 +/- 0.01 (d 96) to 0.17 +/- 0.02 (d 159). The heritability for feed intake and residual feed intake increased in the early stages of the test period and subsequently sharply declined, coinciding with older ages. Heritability estimates for residual daily gain ranged from 0.26 +/- 0.03 (d 188) to 0.42 +/- 0.03 (d 101). Genetic correlations within trait were strongest between adjacent ages but weakened as the interval between ages increased; however, the genetic correlations within all traits tended to strengthen between the extremes of the trajectory. Moderate to strong genetic correlations were evident among live weight, feed intake, and the efficiency traits, particularly in the early stage of the trial period (d 66 to 86), but weakened with age. Results from this study could be implemented into the national genetic evaluation for pigs, providing comprehensive information on the profile of growth and efficiency throughout the growing period of the animal's life, thus helping producers identify genetically superior animals. PMID- 28992030 TI - Monensin and a blend of castor oil and cashew nut shell liquid used in a high concentrate diet abruptly fed to Nellore cattle. AB - Monensin and functional oils (FO) were supplemented to a high-concentrate diet abruptly fed to 12 ruminally cannulated Zebu steers to study their effects on rumen fermentation, blood metabolites, and , , and relative population. A randomized complete block design with repeated measures over time within 2 experimental periods of 21 d each was used. Treatments were a control (CTR; with no additives), FO (included at 400 mg/kg), and monensin included at 30 mg/kg (M30) or 40 mg/kg (M40). All steers were fed the same high-concentrate basal diet, which consisted of 92.25% concentrate. The first 60 h after transition showed a treatment and hour interaction for ruminal propionate proportion ( = 0.028), and no change in acetate molar proportion ( = 0.633), rumen pH ( = 0.370), and time the rumen pH remained below 5.6 ( = 0.242) were observed. The acetate:propionate ratio decreased ( = 0.020) when monensin was fed in both concentrations (2.30 for the M30 treatment and 2.32 for the M40 treatment) compared with when the CTR was fed (2.85), without being different when the FO (2.71) treatment was fed. Only the M30 treatment did not show pH below 5.2 (P=0.047) over the 60 h after the abrupt transition. Within the entire period, DMI ( = 0.008) and mean ruminal pH ( = 0.040) as well as molar proportions of propionate ( = 0.034) and valerate ( = 0.031) had significant interactions between treatment and day. Total VFA concentration was greater ( = 0.017) for the M30 (117.36 m) and CTR treatments (115.77 m) compared with the M40 treatment (105.02 m), without being different for the FO treatment (111.55 m). Treatments did not change feed behavior parameters. Blood HCO ( = 0.006) and total carbon dioxide ( = 0.003) were greater for the M30 (27.8 and 29.3 mmol/L, respectively) and FO treatments (28.3 and 29.7 mmol/L, respectively) compared with the CTR treatment (25.7 and 26.9 mmol/L, respectively). ( < 0.0001) and ( < 0.0001) decreased their population throughout days, whereas ( = 0.026) increased its population. Independent of ciliated protozoa genera, the greatest ( < 0.0001) protozoa counts were observed for the CTR treatment (52.7 * 10/mL), intermediate for the FO treatment (35.3 x10/mL), and least for steers fed monensin in both concentrations (15 * 10/mL for the M30 treatment and 14 * 10/mL for the M40 treatment). Feed additives had different effects to reduce the subacute acidosis. The use of the FO and M40 treatments did not change most of the rumen fermentation variables, especially in the first week after abrupt transition, when the M30 treatment provided higher protection against acidosis. PMID- 28992031 TI - Prediction of the chemical body composition of Nellore and crossbreed bulls. AB - Young Nellore and crossbreed bulls were comparatively slaughtered to generate equation models for predicting the chemical composition of the empty body and carcass from the chemical composition of the Hankins and Howe section (; ). Data were collected from 236 animals from different genetic groups: Nellore, one-half Canchim + one-half Nellore, one-half Angus + one-half Nellore, and one-half Simmental + one-half Nellore, with 48 baseline animals (BW range from 218 to 433 kg) and 188 animals finished in the feedlot (BW range from 356 to 618 kg). The chemical composition prediction equation model was developed for all genetic groups using stepwise regression analysis. Across all animals, the percentages of water and ether extract in the HH section were highly correlated ( < 0.001) with the percentages in the carcass ( = 0.911 and = 0.901, respectively, for water content of the carcass [HOC] and = 0.921 and = 0.921, respectively, for ether extract content of the carcass [EEC]) and empty body ( = 0.937 and = 0.926, respectively, for water content of the empty body [HOEB] and = 0.935 and = 0.939, respectively, for ether extract content of the empty body [EEEB]). The best prediction models were for the traits of empty body weight, HOEB, EEEB, HOC, and EEC. Determination coefficients for predicting the dependent variables obtained from the carcass composition were lower than those obtained from the empty body composition. It was concluded that the chemical composition of the empty body and the carcass can be predicted from the composition of the HH section, using a general equation for different genetic groups. PMID- 28992032 TI - Effects of a multi-strain Bacillus spp. direct-fed microbial and a protease enzyme on growth performance, nutrient digestibility, blood characteristics, fecal microbiota, and noxious gas emissions of grower pigs fed corn-soybean-meal based diets-A meta-analysis. AB - Three studies involving 352 grower pigs were conducted to determine the effects of dietary supplementation with multistrain spp. direct-fed microbial (DFM) and protease, alone or in combination, on growth performance, nutrient digestibility, blood characteristics, fecal microbiota, and noxious gas emissions, and to use a meta-analysis to increase the reliability of the findings. Treatments ( = 4) were set up as a 2 * 2 factorial design with 2 levels of protease (0 and 5.000/6.000 units/kilogram of feed [U/KG]) and 2 levels of DFM (0 and 1.5 * 10 colony forming units/gram of feed [CFU/G]), plus a protease + DFM combination. Pigs were housed in groups of 3 or 4/pen with 8 replicate pens/treatment. Experimental diets were fed for 42 d and feed intake and BW were measured weekly. Fecal samples were collected at d 42 and analyzed to determine apparent total tract digestibility (ATTD). Fecal counts of and coliforms, and noxious gas emissions were measured. Blood samples were taken by anterior vena cava puncture to measure blood urea nitrogen (BUN) and creatinine. Data from the 3 studies were pooled and analyzed as a 2 * 2 factorial using the Fit Model platform of JMP 11 (SAS Inst. Inc., Cary, NC). Means separation was determined using Tukey's honest significant difference test. The main effect of protease and DFM increased: BW at 42 d, overall ADG, and overall G:F compared to the control ( < 0.04). There were no interactions between protease and DFM ( > 0.05); however, the protease + DFM combination was the only treatment to improve ADG and G:F in all phases compared to the control. The main effect of protease increased ATTD of DM, nitrogen (N), and ADF ( < 0.04). The main effect of DFM increased ATTD of DM, N, GE, DE, ADF, and fat ( < 0.02). There was a trend for an interaction between protease and DFM for ATTD of GE and DE ( < 0.08) because the protease + DFM combination increased energy digestibility more than the additive effects of the protease and DFM alone. The main effects of protease and DFM decreased fecal ammonia emissions ( < 0.01), but the protease + DFM combination was the only treatment to decrease ammonia emissions compared to the control. In conclusion, the main effects of protease and DFM improved growth performance and nutrient digestibility compared to the control, but there was a greater additive effect of the protease + DFM combination on energy and N digestibility. PMID- 28992033 TI - Veal calf health on the day of arrival at growers in Ohio. AB - Veal calves are at high risk for disease and mortality in early life. Calves face a number of stressors before arriving at the grower, including long transport times, which may contribute to poor health. Our objectives were to 1) estimate the prevalence of poor health outcomes in veal calves on arrival at growers in Ohio; 2) determine risk factors for health outcomes on arrival, including BW and auction site (spread across 5 states in the Northeastern United States); and 3) determine if health outcomes on arrival predict early mortality. A physical examination was conducted on approximately 30 calves (mean of 45.9 kg [SD 3.0]) from 12 cohorts ( = 383 calves). Exams included a blood sample to determine packed cell volume (an estimate of dehydration using a cutoff > 46%) and total protein (an estimate failure of passive transfer using a cutoff < 5.5 g/dL and 6.0 g/dL to account for dehydration). Diarrhea, respiratory disease, depression, navel inflammation, and a skin tent test (a second indicator of dehydration) were also recorded. Mortality within 4 wk of age was collected from farm records. Descriptive statistics were used to describe the prevalence of calves with poor health outcomes on arrival. Generalized linear mixed models were used to identify risk factors for poor health on arrival and assess if poor health increased the incidence risk of mortality. Upon arrival, 6% (95% confidence interval 4.4 to 7.6%) of calves had failure of passive transfer using a cut-off of 5.5 g/dL, and 22.5% (18.1 to 26.8%) had failure of passive transfer using a cut-off of 5.5 g/dL, and 22.5% (18.1 to 26.8%) had failure of passive transfer using a cut-off of 6.0%; 14% (9.1 to 18.8%) had diarrhea, 0.5% (0 to 1.3%) had respiratory disease, 14% (8.5 to 19.3%) were depressed, and 27% (22.7 to 30.7%) had inflamed navels. In addition, 35.1% (23.5 to 46.6%) of calves were dehydrated using a skin tent test, but only 1.3% (0.0 to 2.9%) were dehydrated based on the packed cell volume threshold. Auction site was associated with depression on arrival ( = 0.008) and tended to be associated with skin tent on arrival ( = 0.08). None of the health variables were predictors of early mortality; however, mortality was generally low for all cohorts (4.3%; range 1.7 to 6.8%). These results estimate the prevalence of dehydration, diarrhea, navel inflammation, and depression in veal calves on arrival at growers and demonstrate that some health outcomes are dependent on auction site. We conclude that there are many opportunities to intervene to improve their health and welfare before the calves arrive at the grower. PMID- 28992034 TI - The effect of energy restriction on fatty acid profiles of longissimus dorsi and tissue adipose depots in sheep. AB - Sheep production systems in northwest China depend mostly on natural grasslands. Seasonal growth and maturity fluctuations can cause periodical restrictions in food quality and quantity. These fluctuations, in turn, result in variability in fat deposition and fatty acid profiles in different fat depots. Consequently, the study objective was to compare fat deposition, intramuscular fat (IMF) percentage and fatty acid profiles of the longissimus dorsi (LD), kidney fat (KF), tail fat (TF), and subcutaneous fat (SF) in lambs under ME restrictions similar to seasonal changes observed in the natural grasslands of northwest China. Nineteen male Dorper * Small Tailed Han lambs were assigned to 2 treatments, a control (CON) fed at 1.0 MJ / W * d and restricted (RES) by restricting ME sequentially every 30 d (0.56 MJ / W * d, 0.84 / W * d, 1.0 MJ / W * d, 0.84 MJ / W * d, 0.56 MJ / W * d, 0.28 MJ / W * d). All lambs were harvested at the end of the 180 d experimental period. Compared to CON fed lambs, restricting ME resulted in lesser IMF, fat deposition indexes ( < 0.05) except testicular and heart fat and greater ( < 0.05) SFA in LD, KF, and TF depots. The RES fed lambs had greater ( < 0.05) 3 PUFA, eicosatrienoic acid (C20:3n3), eicosapentaenoic acid (C20:5n3, EPA), and trans-linolelaidic acid (C18:2n6t) in LD muscle. The conjugated linoleic acids (CLA) content was greater in the SF depots of the CON fed lambs compared to the RES fed lambs. Fatty acid ratios (unsaturated fatty acid; USFA:SFA, MUFA:SFA, PUFA:SFA), and percentage USFA in RES fed lambs were lesser in muscle and adipose tissue compared to CON fed lambs ( < 0.05), except SF depots. In RES fed lambs, EFA were less ( < 0.05) in LD and KF depots and the ratios of functional fatty acids were lesser in LD and some adipose tissues ( < 0.05), including lesser n 6:n-3 in KF and SF ( < 0.05) depots, lesser USFA, SFA, MUFA, SFA in LD, KF, and TF ( < 0.05) depots, and lesser PUFA and SFA in LD and TF ( < 0.05) depots. Results from this research demonstrate that sequential energy restriction, as might be experience during seasonal forage quality and quantity changes in natural grasslands, result in lesser intramuscular fat with associated lesser quality, as well as, changes in fatty acid composition in different fat depots, which has implications for both meat quality and animal physiological functions. PMID- 28992035 TI - Does Type of Residential Housing Matter for Depressive Symptoms in the Aftermath of a Disaster? Insights From the Great East Japan Earthquake and Tsunami. AB - The 2011 Great East Japan Earthquake and Tsunami resulted in widespread property destruction and over 250,000 displaced residents. We sought to examine whether the type of housing arrangement available to the affected victims was associated with a differential incidence of depressive symptoms. In this prospective cohort study, which comprised participants aged >=65 years from Iwanuma as a part of the Japan Gerontological Evaluation Study, we had information about the residents' mental health both before the disaster in 2010 and 2.5 years afterward. The Geriatric Depression Scale was used. Type of accommodation after the disaster was divided into 5 categories: no move, prefabricated housing (temporary housing), existing private accommodations (temporary apartment), newly established housing, and other. Poisson regression analysis was adopted, with and without multiple imputation. Among the 2,242 participants, 16.2% reported depressive symptoms at follow-up. The adjusted rate ratio for depressive symptoms among persons moving into prefabricated housing, compared with those who did not, was 2.07 (95% confidence interval: 1.45, 2.94). Moving into existing private accommodations or other types of accommodations was not associated with depression. The relationship between living environment and long-term mental health should be considered for disaster recovery planning. PMID- 28992036 TI - Associations Between Sedentary Behaviors and Cognitive Function: Cross-Sectional and Prospective Findings From the UK Biobank. AB - We investigated the cross-sectional and prospective associations between different sedentary behaviors and cognitive function in a large sample of adults with data stored in the UK Biobank. Baseline data were available for 502,643 participants (2006-2010, United Kingdom). Cognitive tests included prospective memory (baseline only: n = 171,585), visual-spatial memory (round 1: n = 483,832; round 2: n = 482,762), fluid intelligence (n = 165,492), and short-term numeric memory (n = 50,370). After a mean period of 5.3 years, participants (numbering from 12,091 to 114,373, depending on the test) also provided follow-up cognitive data. Sedentary behaviors (television viewing, driving, and nonoccupational computer-use time) were measured at baseline. At baseline, both television viewing and driving time were inversely associated with cognitive function across all outcomes (e.g., for each additional hour spent watching television, the total number of correct answers in the fluid intelligence test was 0.15 (99% confidence interval: 0.14, 0.16) lower. Computer-use time was positively associated with cognitive function across all outcomes. Both television viewing and driving time at baseline were positively associated with the odds of having cognitive decline at follow-up across most outcomes. Conversely, computer-use time at baseline was inversely associated with the odds of having cognitive decline at follow-up across most outcomes. This study supports health policies designed to reduce television viewing and driving in adults. PMID- 28992038 TI - Understanding Female Receiver Psychology in Reproductive Contexts. AB - Mate choice decision-making requires four components: sensory, cognitive, motivation, and salience. During the breeding season, the neural mechanisms underlying these components act in concert to radically transform the way a female perceives the social cues around her as well as the way in which cognitive and motivational processes influence her decision to respond to courting males. The role of each of these four components in mate choice responses will be discussed here as well as the brain regions involved in regulating each component. These components are not independent, modular systems. Instead, they are dependent on one another. This review will discuss the many ways in which these components interact and affect one another. The interaction of these components, however, ultimately leads back to a few key neuromodulators that thread motivation, sensory, salience, and cognitive components into a set of inter-dependent processes. These neuromodulators are estrogens and catecholamines. This review will highlight the need to understand estrogens in reproductive contexts not just as simply a 'sexual motivation modulator' or catecholamines as 'cognitive regulators' but as neuromodulators that work together to fully transform a non-breeding female into a completely reproductive female displaying: heightened sexual interest in courting males, greater arousal and selective attention toward courtship signals, improved signal detection and discrimination abilities, enhanced contextual signal memory, and increased motivation to respond to signals assigned incentive salience. The aim of this review is to build a foundation in which to understand the brain regions associated with cognitive, sensory, motivational, and signal salience not as independently acting systems but as a set of interacting processes that function together in a context-appropriate manner. PMID- 28992037 TI - Selecting Shrinkage Parameters for Effect Estimation: The Multi-Ethnic Study of Atherosclerosis. AB - We present a method for improving estimation in linear regression models in samples of moderate size, using shrinkage techniques. Our work connects the theory of causal inference, which describes how variable adjustment should be performed with large samples, with shrinkage estimators such as ridge regression and the least absolute shrinkage and selection operator (LASSO), which can perform better in sample sizes seen in epidemiologic practice. Shrinkage methods reduce mean squared error by trading off some amount of bias for a reduction in variance. However, when inference is the goal, there are no standard methods for choosing the penalty "tuning" parameters that govern these tradeoffs. We propose selecting the penalty parameters for these shrinkage estimators by minimizing bias and variance in future similar data sets drawn from the posterior predictive distribution. Our method provides both the point estimate of interest and corresponding standard error estimates. Through simulations, we demonstrate that it can achieve better mean squared error than using cross-validation for penalty parameter selection. We apply our method to a cross-sectional analysis of the association between smoking and carotid intima-media thickness in the Multi Ethnic Study of Atherosclerosis (multiple US locations, 2000-2002) and compare it with similar analyses of these data. PMID- 28992039 TI - Environmental Causation of Turtle Scute Anomalies in ovo and in silico. AB - The turtle shell is often described as an evolutionary novelty that facilitated the radiation of the clade Testudines. The scutes, or keratinous plates, of the turtle shell are hypothesized to be patterned by reaction-diffusion dynamics, and this property of their development provides explanatory power to mechanisms of anomalous variation. A mathematical model of scute development predicts that anomalous variation in the phylogenetically stable pattern of scutes is achieved by environmental influence on the developmental program. We test this prediction with data on patterns of scute variation from natural nests and controlled incubation of sea turtle eggs in Florida and Western Australia. We find that high temperatures are sufficient to produce anomalous patterns in turtle scutes, and that this correlation is even stronger when conditions are dry. Furthermore, we find that the patterns of variation are not random; greater anomalous variation is found in the midline vertebral scutes and during a critical period of turtle development. PMID- 28992040 TI - Changing MADS-Box Transcription Factor Protein-Protein Interactions as a Mechanism for Generating Floral Morphological Diversity. AB - Flowers display fantastic morphological diversity. Despite extreme variability in form, floral organ identity is specified by a core set of deeply conserved proteins-the floral MADS-box transcription factors. This indicates that while core gene function has been maintained, MADS-box transcription factors have evolved to regulate different downstream genes. Thus, the evolution of gene regulation downstream of the MADS-box transcription factors is likely central to the evolution of floral form. Gene regulation is determined by the combination of transcriptional regulators present at a particular cis-regulatory element at a particular time. Therefore, the interactions between transcription factors can be of profound importance in determining patterns of gene regulation. Here, after a short primer on flowers and floral morphology, I discuss the centrality of protein-protein interactions to MADS-box transcription factor function, and review the evidence that the evolution of MADS-box protein-protein interactions is a key driver in the evolution of gene regulation downstream of the MADS-box genes. PMID- 28992041 TI - Peripheral tissue levels and molecular species compositions of N-acyl phosphatidylethanolamine and its metabolites in mice lacking N-acyl phosphatidylethanolamine-specific phospholipase D. AB - N-acylethanolamines (NAEs), a class of lipid mediators, are produced from N-acyl phosphatidylethanolamine (NAPE) by several pathways, including the direct release by NAPE-specific phospholipase D (NAPE-PLD) or the multistep pathway via sn glycero-3-phospho-N-acylethanolamine (Gp-NAE). Using liquid chromatography-tandem mass spectrometry, we compared peripheral tissue levels of NAPE, Gp-NAE and NAE in NAPE-PLD-deficient (NAPE-PLD-/-) and wild type (WT) mice. NAPE-PLD was suggested to play a major role in the NAPE degradation in heart, kidney, and liver, but not in jejunum, because the NAPE levels except jejunum were significantly higher in NAPE-PLD-/- mice than in WT mice. The deletion of NAPE PLD failed to alter the NAE levels of these tissues, suggesting its limited role in the NAE production. The enzyme assays with tissue homogenates confirmed the presence of NAPE-PLD-independent pathways in these peripheral tissues. Gp-NAE species having an acyl moiety with 22 carbons and 6 double bonds was enriched in these peripheral tissues. As for sn-2 acyl species of NAPE, 18:2-acyl-containing NAPE species were predominant over 18:1-containing species in heart, liver, and jejunum. Our results show that both molecular species composition of NAPE, NAE and Gp-NAE and their dependencies on Napepld are different among the peripheral tissues, suggesting that each tissue has distinct metabolic pathways and these NAE-containing lipids play tissue-specific roles. PMID- 28992042 TI - Prominent IgE-binding and cytokine-inducing capacities of a newly cloned N terminal region of Der f 14, an apolipophorin-like house dust mite allergen. AB - We previously characterized a 177-kDa allergen, M-177, from Dermatophagoides farinae. Thereafter, a counterpart to M-177 for Euroglyphus maynei was cloned as Eur m 14, and its sequence revealed that two environmental allergens, Mag 1 and Mag 3, are digested fragments of M-177. The aims of this study were to clone the cDNA of Der f 14 corresponding to M-177 and to elucidate the allergenic capacities of the N-terminal fragment of Der f 14 (Der f 14-N). Recombinant allergens were produced as trigger-factor-fused proteins in Escherichia coli. Der f 14-N showed the highest IgE-binding frequency among Der f 14-derived fragments in patients allergic to house dust mite by enzyme-linked immunosorbent assay. Der f 14-N showed the highest capacity to induce cell proliferation in murine lymphocyte and human peripheral mononuclear cells among Der f 14-derived fragments. Der f 14-N induced IL-13, IFN-gamma and IL-17 production more than Der f 1 and Der f 2 in mouse, and induced IL-5 and IFN-gamma production at levels comparable to those of Der f 1 and Der f 2 in some patients. The high prevalence of IgE binding to the Der f 14-N indicates that it could be an important mite allergen. PMID- 28992043 TI - Conjugation of two RNA aptamers improves binding affinity to AML1 Runt domain. AB - To develop a high-affinity aptamer against AML1 Runt domain, two aptamers were conjugated based on their structural information. The newly designed aptamer Apt14 was generated by the conjugation of two RNA aptamers (Apt1 and Apt4) obtained by SELEX against AML1 Runt domain, resulting in improvement in its binding performance. The residues of AML1 Runt domain in contact with Apt14 were predicted in silico and confirmed by mutation and NMR analyses. It was suggested that the conjugated internal loop renders additional contacts and is responsible for the enhancement in the binding affinity. Conjugation of two aptamers that bind to different sites of the target protein is a facile and robust strategy to develop an aptamer with higher performance. PMID- 28992044 TI - Formation of metastable phases in Zr-ion-irradiated Al2O3 upon thermal annealing. AB - Formation of metastable phases in Zr-ion-irradiated corundum alumina (Al2O3) upon thermal annealing was examined using transmission electron microscopy. A metastable cubic spinel phase was formed in the topmost layer of the as irradiated microstructure. During thermal annealing at temperatures ranging from 1073 to 1273 K, this spinel layer grew in extent via an unusual corundum-to spinel phase transformation. A normal spinel-to-corundum phase transformation was observed at post-irradiation annealing temperatures greater than 1473 K. In addition, ZrO2 nanocrystals embedded in alpha-Al2O3 were observed to form at these higher temperatures. High-resolution transmission electron microscopy observations and electron diffraction experiments revealed that the structure of the ZrO2 precipitates observed in this study are consistent with a high-pressure metastable orthorhombic phase of ZrO2 known as the Ortho-I phase. PMID- 28992045 TI - A Descriptive Analysis of the Educational Perceptions, Professional Identity, and Professional Practices of Dual-Trained Music Therapists as Counselors. AB - Background: Given the rise in music therapy master's programs that offer dual degrees in music therapy and counseling or programs that satisfy state mental health counseling licensure laws, the professional counseling field is playing an increased role in the advanced education and professional practices of music therapists. Objective: To identify factors that lead music therapists to pursue advanced education with an emphasis in professional counseling, perceptions about benefits and drawbacks for three advanced degree options (i.e., music therapy, counseling, and music therapy/counseling dual degree), and describe the professional practices and identity of dual-trained music therapists as counselors. Methods: A convenience sample of music therapists (n = 123) who held board certification, and held a master's degree or higher that emphasized professional counseling, completed an online survey. We used descriptive statistics to analyze categorical and numeric survey data. Results: Eligibility for licensure as a professional counselor was the most important decisional factor in selecting a specific master's degree program. Respondents also reported favorable perceptions of the dual degree in music therapy and counseling. With regard to professional practice and identity, respondents reported high use of verbal processing techniques alongside music therapy interventions, and dual trained music therapists retained their professional identity as a music therapist. Conclusions: The reported view of licensure in a related field as beneficial and frequent use of verbal processing techniques warrants future study into the role of counseling in the advanced training of music therapists. Given contradictory findings across studies, we recommend investigators also explore how a degree in a related field affects career longevity of music therapists. PMID- 28992046 TI - Phosphorylated E2F1 is stabilized by nuclear USP11 to drive Peg10 gene expression and activate lung epithelial cells. AB - Phosphorylation affects ubiquitination, stability, and activity of transcriptional factors, thus regulating various cellular functions. E2F transcriptional factor 1 (E2F1) regulates paternally expressed imprinted gene 10 (Peg10) expression, thereby promoting cell proliferation. However, the effect of E2F1 stability on Peg10 expression and the molecular regulation of E2F1 stability by its phosphorylation have not been well demonstrated. Here, we describe a new pathway in which phosphorylation of E2F1 by GSK3beta increases E2F1 association with the deubiquitinating enzyme, ubiquitin-specific protease 11 (USP11), which removes K63-linked ubiquitin chains thereby preventing E2F1 degradation in the nuclei. Downregulation of USP11 increases E2F1 ubiquitination and reduces E2F1 stability and protein levels, thereby decreasing Peg10 mRNA levels. Physiologically, USP11 depletion suppresses cell proliferation and wound healing in lung epithelial cells, and these effects are reversed by E2F1 and PEG10 overexpression. Thus, our study reveals a new molecular model that phosphorylation promotes substrate stability through increasing its association with a deubiquitinating enzyme. The data suggest that GSK3beta and USP11 act in concert to modulate E2F1 abundance and PEG10 expression in lung epithelial cells to affect cell wound healing. This study provides new therapeutic targets to lessen lung injury by improving lung epithelial cell repair and remodeling after injury. PMID- 28992047 TI - Preliminary comparison of the registration effect of 4D-CBCT and 3D-CBCT in image guided radiotherapy of Stage IA non-small-cell lung cancer. AB - In this study, we compared the registration effectiveness of 4D cone-beam computed tomography (CBCT) and 3D-CBCT for image-guided radiotherapy in 20 Stage IA non-small-cell lung cancer (NSCLC) patients. Patients underwent 4D-CBCT and 3D CBCT immediately before radiotherapy, and the X-ray Volume Imaging software system was used for image registration. We performed automatic bone registration and soft tissue registration between 4D-CBCT or 3D-CBCT and 4D-CT images; the regions of interest (ROIs) were the vertebral body on the layer corresponding to the tumor and the internal target volume region. The relative displacement of the gross tumor volume between the 4D-CBCT end-expiratory phase sequence and 4D-CT was used to evaluate the registration error. Among the 20 patients (12 males, 8 females; 35-67 years old; median age, 52 years), 3 had central NSCLC and 17 had peripheral NSCLC, 8 in the upper or middle lobe and 12 in the lower lobe (maximum tumor diameter range, 18-27 mm). The internal motion range in three-dimensional space was 12.52 +/- 2.65 mm, accounting for 47.8 +/- 15.3% of the maximum diameter of each tumor. The errors of image-guided registration using 4D-CBCT and 3D-CBCT on the x (left-right), y (superior-inferior), z (anterior-posterior) axes, and 3D space were 0.80 +/- 0.21 mm and 1.08 +/- 0.25 mm, 2.02 +/- 0.46 mm and 3.30 +/- 0.53 mm, 0.52 +/- 0.16 mm and 0.85 +/- 0.24 mm, and 2.25 +/- 0.44 mm and 3.59 +/- 0.48 mm (all P < 0.001), respectively. Thus, 4D-CBCT is preferable to 3D-CBCT for image guidance in small pulmonary tumors because 4D-CBCT can reduce the uncertainty in the tumor location resulting from internal motion caused by respiratory movements, thereby increasing the image-guidance accuracy. PMID- 28992049 TI - Relations of Demographic and Clinical Factors With Cardiovascular Autonomic Function in a Population-Based Study: An Assessment By Quantile Regression. AB - BACKGROUND: The relationships of many factors with cardiovascular autonomic function (CVAF) outcome parameters may not be uniform across the entire distribution of the outcome. We examined how demographic and clinical factors varied with different subgroups of CVAF parameters. METHODS: Quantile regression was applied to a cross-sectional analysis of 4,167 adults (56% male; age range, 50-84 years) from 4 ethnic groups (3,419 New Zealand European, 303 Pacific, 227 Maori, and 218 South Asian) and without diagnosed cardiac arrhythmia. Pulse rate variability (root mean square of successive differences (RMSSD) and SD of pulse intervals) and baroreflex sensitivity were response variables. Independent variables were age, sex, ethnicity, brachial and aortic blood pressure (BP) variables, body mass index (BMI), and diabetes. RESULTS: Ordinary linear regression showed that age, sex, Pacific and Maori ethnicity, BP variables, BMI, and diabetes were associated with CVAF parameters. But quantile regression revealed that, across CVAF percentiles, the slopes for these relationships: (i) varied by more than 10-fold in several cases and sometimes changed direction and (ii) noticeably differed in magnitude often (by >3-fold in several cases) compared to ordinary linear regression coefficients. For instance, age was inversely associated with RMSSD at the 10th percentile of this parameter (beta = 0.12 ms/year, 95% confidence interval = -0.18 to -0.09 ms/year) but had a positive relationship at the 90th percentile (beta = 3.17 ms/year, 95% confidence interval = 2.50 to 4.04 ms/year). CONCLUSIONS: The relationships of demographic and clinical factors with CVAF parameters are, in many cases, not uniform. Quantile regression provides an improved assessment of these associations. PMID- 28992048 TI - Comparative whole-genome analysis reveals artificial selection effects on Ustilago esculenta genome. AB - Ustilago esculenta, infects Zizania latifolia, and induced host stem swollen to be a popular vegetable called Jiaobai in China. It is the long-standing artificial selection that maximizes the occurrence of favourable Jiaobai, and thus maintaining the plant-fungi interaction and modulating the fungus evolving from plant pathogen to entophyte. In this study, whole genome of U. esculenta was sequenced and transcriptomes of the fungi and its host were analysed. The 20.2 Mb U. esculenta draft genome of 6,654 predicted genes including mating, primary metabolism, secreted proteins, shared a high similarity to related Smut fungi. But U. esculenta prefers RNA silencing not repeat-induced point in defence and has more introns per gene, indicating relatively slow evolution rate. The fungus also lacks some genes in amino acid biosynthesis pathway which were filled by up regulated host genes and developed distinct amino acid response mechanism to balance the infection-resistance interaction. Besides, U. esculenta lost some surface sensors, important virulence factors and host range-related effectors to maintain the economic endophytic life. The elucidation of the U. esculenta genomic information as well as expression profiles can not only contribute to more comprehensive insights into the molecular mechanism underlying artificial selection but also into smut fungi-host interactions. PMID- 28992051 TI - New insights into the regulation of leaf senescence in Arabidopsis. AB - Plants undergo developmental changes throughout their life history. Senescence, the final stage in the life history of a leaf, is an important and unique developmental process whereby plants relocate nutrients from leaves to other developing organs, such as seeds, stems, or roots. Recent attempts to answer fundamental questions about leaf senescence have employed a combination of new ideas and advanced technologies. As senescence is an integral part of a plant's life history that is linked to earlier developmental stages, age-associated leaf senescence may be analysed from a life history perspective. The successful utilization of multi-omics approaches has resolved the complicated process of leaf senescence, replacing a component-based view with a network-based molecular mechanism that acts in a spatial-temporal manner. Senescence and death are critical for fitness and are thus evolved characters. Recent efforts have begun to focus on understanding the evolutionary basis of the developmental process that incorporates age information and environmental signals into a plant's survival strategy. This review describes recent insights into the regulatory mechanisms of leaf senescence in terms of systems-level spatiotemporal changes, presenting them from the perspectives of life history strategy and evolution. PMID- 28992050 TI - Clinical outcomes of 125I brachytherapy with and without external-beam radiation therapy for localized prostate cancer: results from 300 patients at a single institution in Japan. AB - The aim of this study was to determine the outcomes and adverse events for 300 men with prostate cancer treated with 125iodine (125I) brachytherapy with and without external-beam radiation therapy (EBRT) at a single institution in Japan. Between February 2005 and November 2011, 300 consecutive patients with clinically localized prostate cancer were treated with 125I brachytherapy at the Nagoya University Hospital. A total of 271 men were treated with implants with doses of 145 Gy, and 29 men were treated with implants with doses of 110 Gy combined with EBRT (40-50 Gy/20-25 fractions). The median patient age was 69 years (range, 53 83 years). The median follow-up period was 53 months (range, 5-99 months). According to the National Comprehensive Cancer Network risk classification, 132 men (44%) had low-risk, 147 men (29%) had intermediate-risk and 21 men (7%) had high-risk disease. The 5-year overall survival rate, biochemical relapse-free survival rate, and disease-specific survival rates were 93.5%, 97.3% and 98.5%, respectively. Two men (0.6%) died of prostate cancer and 10 men (3.3%) died of other causes. Seventeen men (5.6%) experienced Grade 2 rectal bleeding in all: 12 (41.4%) of 29 in brachytherapy with EBRT, and 5 (1.8%) of 271 in brachytherapy alone. The rates of Grade 2 and 3 genitourinary toxicity were 1.0% and 1.7%, respectively. Excellent local control was achieved at our hospital for localized prostate cancer with 125I brachytherapy with and without EBRT. Gastrointestinal and genitourinary toxicities were acceptable. PMID- 28992052 TI - Dose-rate effect of ultrashort electron beam radiation on DNA damage and repair in vitro. AB - Laser-generated electron beams are distinguished from conventional accelerated particles by ultrashort beam pulses in the femtoseconds to picoseconds duration range, and their application may elucidate primary radiobiological effects. The aim of the present study was to determine the dose-rate effect of laser-generated ultrashort pulses of 4 MeV electron beam radiation on DNA damage and repair in human cells. The dose rate was increased via changing the pulse repetition frequency, without increasing the electron energy. The human chronic myeloid leukemia K-562 cell line was used to estimate the DNA damage and repair after irradiation, via the comet assay. A distribution analysis of the DNA damage was performed. The same mean level of initial DNA damages was observed at low (3.6 Gy/min) and high (36 Gy/min) dose-rate irradiation. In the case of low-dose-rate irradiation, the detected DNA damages were completely repairable, whereas the high-dose-rate irradiation demonstrated a lower level of reparability. The distribution analysis of initial DNA damages after high-dose-rate irradiation revealed a shift towards higher amounts of damage and a broadening in distribution. Thus, increasing the dose rate via changing the pulse frequency of ultrafast electrons leads to an increase in the complexity of DNA damages, with a consequent decrease in their reparability. Since the application of an ultrashort pulsed electron beam permits us to describe the primary radiobiological effects, it can be assumed that the observed dose-rate effect on DNA damage/repair is mainly caused by primary lesions appearing at the moment of irradiation. PMID- 28992053 TI - Molecular and Neuroendocrine Approaches to Understanding Trade-offs: Food, Sex, Aggression, Stress, and Longevity-An Introduction to the Symposium. AB - Life history strategies are composed of multiple fitness components, each of which incurs costs and benefits. Consequently, organisms cannot maximize all fitness components simultaneously. This situation results in a dynamic array of trade-offs in which some fitness traits prevail at the expense of others, often depending on context. The identification of specific constraints and trade-offs has helped elucidate physiological mechanisms that underlie variation in behavioral and physiological life history strategies. There is general recognition that trade-offs are made at the individual and population level, but much remains to be learned concerning the molecular neuroendocrine mechanisms that underlie trade-offs. For example, we still do not know whether the mechanisms that underlie trade-offs at the individual level relate to trade-offs at the population level. To advance our understanding of trade-offs, we organized a group of speakers who study neuroendocrine mechanisms at the interface of traits that are not maximized simultaneously. Speakers were invited to represent research from a wide range of taxa including invertebrates (e.g., worms and insects), fish, nonavian reptiles, birds, and mammals. Three general themes emerged. First, the study of trade-offs requires that we investigate traditional endocrine mechanisms that include hormones, neuropeptides, and their receptors, and in addition, other chemical messengers not traditionally included in endocrinology. The latter group includes growth factors, metabolic intermediates, and molecules of the immune system. Second, the nomenclature and theory of neuroscience that has dominated the study of behavior is being re-evaluated in the face of evidence for the peripheral actions of so-called neuropeptides and neurotransmitters and the behavioral repercussions of these actions. Finally, environmental and ecological contexts continue to be critical in unmasking molecular mechanisms that are hidden when study animals are housed in enclosed spaces, with unlimited food, without competitors or conspecifics, and in constant ambient conditions. PMID- 28992054 TI - Metabolomics of laminae and midvein during leaf senescence and source-sink metabolite management in Brassica napus L. leaves. AB - Leaf senescence is a long developmental process important for nutrient management and for source to sink remobilization. Constituents of the mesophyll cells are progressively degraded to provide nutrients to the rest of the plant. Up to now, studies on leaf senescence have not paid much attention to the role of the different leaf tissues. In the present study, we dissected leaf laminae from the midvein to perform metabolite profiling. The laminae mesophyll cells are the source of nutrients, and in C3 plants they contain Rubisco as the most important nitrogen storage pool. Veins, rich in vasculature, are the place where all the nutrients are translocated, and sometimes interconverted, before being exported through the phloem or the xylem. The different metabolic changes we observed in laminae and midvein with ageing support the idea that the senescence programme in these two tissues is different. Important accumulations of metabolites in the midvein suggest that nutrient translocations from source leaves to sinks are mainly controlled at this level. Carbon and nitrogen long-distance molecules such as fructose, glucose, aspartate, and asparagine were more abundant in the midvein than in laminae. In contrast, sucrose, glutamate, and aspartate were more abundant in laminae. The concentrations of tricarboxylic acid (TCA) compounds were also lower in the midvein than in laminae. Since nitrogen remobilization increased under low nitrate supply, plants were grown under two nitrate concentrations. The results revealed that the senescence-related differences were mostly similar under low and high nitrate conditions except for some pathways such as the TCA cycle. PMID- 28992055 TI - Amphotericin B concentrations in healthy mallard ducks (Anas platyrhynchos) following a single intratracheal dose of liposomal amphotericin B using an atomizer. AB - Aspergillosis is a fungal infection that primarily affects the respiratory tract. Amphotericin B has broad antifungal activity and is commonly used to treat aspergillosis, a fungal pneumonia that is a common sequela in oiled waterfowl as well as other birds in wildlife rehabilitation. Pharmacokinetic parameters of nebulized amphotericin B in an avian model have been reported, but those of direct intratracheal delivery have yet to be established. The objective of this study was to evaluate if a single 3 mg/kg dose of liposomal amphotericin B delivered intratracheally using a commercial atomizer would achieve plasma and lung tissue concentrations exceeding targeted minimum inhibitory concentrations (MIC) for Aspergillus species in adult mallard ducks (Anas platyrhynchos). Following intratracheal delivery, amphotericin B was present in lung parenchyma at concentrations above the targeted MIC of 1 MUg/g for up to 9 days post administration; however, distribution of the drug was uneven, with the majority of the drug concentrated in one lung lobe. Concentrations in the contralateral lung lobe and the kidneys were above the targeted MIC 1 day after administration but declined exponentially with a half-life of approximately 2 days. Plasma concentrations were never above the targeted MIC. Histological examination of the trachea, bronchi, lungs, heart, liver, and kidneys did not reveal any toxic changes. Using a commercial atomizer, intratracheal delivery of amphotericin B at 3 mg/kg resulted in lung parenchyma concentrations above 1 MUg/ml with no discernable systemic effects. Further studies to establish a system of drug delivery to both sides of the pulmonary parenchyma need to be performed, and the efficacy of this treatment for disease prevention remains to be determined. PMID- 28992056 TI - A world of opportunities with nanopore sequencing. AB - Oxford Nanopore Technologies' MinION sequencer was launched in pre-release form in 2014 and represents an exciting new sequencing paradigm. The device offers multi-kilobase reads and a streamed mode of operation that allows processing of reads as they are generated. Crucially, it is an extremely compact device that is powered from the USB port of a laptop computer, enabling it to be taken out of the lab and facilitating previously impossible in-field sequencing experiments to be undertaken. Many of the initial publications concerning the platform focused on provision of tools to access and analyse the new sequence formats and then demonstrating the assembly of microbial genomes. More recently, as throughput and accuracy have increased, it has been possible to begin work involving more complex genomes and metagenomes. With the release of the high-throughput GridION X5 and PromethION platforms, the sequencing of large genomes will become more cost efficient, and enable the leveraging of extremely long (>100 kb) reads for resolution of complex genomic structures. This review provides a brief overview of nanopore sequencing technology, describes the growing range of nanopore bioinformatics tools, and highlights some of the most influential publications that have emerged over the last 2 years. Finally, we look to the future and the potential the platform has to disrupt work in human, microbiome, and plant genomics. PMID- 28992058 TI - Species distribution, virulence factors, and antifungal susceptibility among Candida parapsilosis complex isolates from clinical specimens at Siriraj Hospital, Thailand, from 2011 to 2015. AB - The Candida parapsilosis complex has been described as the second or third most common yeast species isolated from patients with bloodstream infections worldwide. This complex consists of three species: C. parapsilosis sensu stricto, C. orthopsilosis, and C. metapsilosis. The distribution of species in this complex has never been studied in Thailand. Here we investigated the molecular epidemiology, in vitro on virulence factors, and antifungal susceptibility profiles of isolates of these three species collected from patients in Siriraj Hospital, Thailand, from 2011 to 2015. Of the 96 C. parapsilosis complex isolates analyzed, 66 (68.75%) were identified as C. parapsilosis sensu stricto, 28 (29.17%) as C. orthopsilosis, and two (2.08%) as C. metapsilosis. Most strains were isolated from blood (81.25%). Proteinase activity was only detected in four (6.06%) and two (7.14%) isolates of C. parapsilosis sensu stricto and C. orthopsilosis, respectively. Sixty (90.91%) isolates of C. parapsilosis sensu stricto, 12 (42.86%) isolates of C. orthopsilosis, and all C. metapsilosis isolates showed phospholipase activity. Psuedohyphae formation was only detected in 33 (50%) and 15 (53.57%) isolates of C. parapsilosis sensu stricto and C. orthopsilosis, respectively. All isolates were susceptible to caspofungin. Most (85-100%) isolates were susceptible to antifungal drugs, but 3.13 - 6.25% were resistant to voriconazole and fluconazole. In conclusion, our findings revealed that C. parapsilosis sensu stricto was the most common species among clinical isolates of the C. parapsilosis complex, and the most commonly used antifungal agents generally exhibited good in vitro activity against these strains. PMID- 28992059 TI - The human NAIP-NLRC4-inflammasome senses the Pseudomonas aeruginosa T3SS inner rod protein. AB - While NLRC4-dependent sensing of intracellular Gram-negative pathogens such as Salmonella enterica serovar typhimurium is a beneficial host response, NLRC4 dependent sensing of the Pseudomonas aeruginosa type 3 secretion system (T3SS) has been shown to be involved in pathogenicity. In mice, different pathogen associated microbial patterns are sensed by the combination of the NLRC4 inflammasome with different neuronal apoptosis inhibitory proteins (NAIPs). NAIP2 is involved in sensing PscI, an inner-rod protein of the P. aeruginosa T3SS. Surprisingly, only a single human NAIP (hNAIP) has been found. Moreover, there is no description of hNAIP-NLRC4 inflammasome recognition of T3SS inner-rod proteins in humans. Here, we show that the P. aeruginosa T3SS inner-rod protein PscI and needle protein PscF are both sensed by the hNAIP-NLRC4 inflammasome in human macrophages and PBMCs from healthy donors, allowing caspase-1 and IL-1beta maturation and resulting in a robust inflammatory response. TLR4 and TLR2 are involved in redundantly sensing these two T3SS components. PMID- 28992060 TI - Heterozygosity of mitogen-activated protein kinase organizer 1 ameliorates diabetic nephropathy and suppresses epithelial-to-mesenchymal transition-like changes in db/db mice. AB - Background: Progressive diabetic nephropathy (DN) is characterized by tubulointerstitial fibrosis that is caused by accumulation of extracellular matrix. Induced by several factors, matrix-producing myofibroblasts may to some extent originate from tubular cells by epithelial-to-mesenchymal transition (EMT). Although previous data document that activation of hypoxia-inducible factor (HIF) signalling can be renoprotective in acute kidney disease, this issue remains controversial in chronic kidney injury. Here, we studied whether DN and EMT-like changes are ameliorated in a mouse model of type 2 diabetes mellitus with increased stability and activity of the HIF. Methods: We used db/db mice that were crossed with transgenic mice expressing reduced levels of mitogen activated protein kinase organizer 1 (MORG1), a scaffold protein interacting with prolyl hydroxylase domain 3 (PHD3), because of deletion of one MORG1 allele. Results: We found significantly reduced nephropathy in diabetic MORG1+/- heterozygous mice compared with the diabetic wild-types (db/dbXMORG1+/+). Furthermore, we demonstrated that EMT-like changes in the tubulointerstitium of diabetic wild-type MORG1+/+ mice are present, whereas diabetic mice with reduced expression of MORG1 showed significantly fewer EMT-like changes. Conclusions: These findings reveal that a deletion of one MORG1 allele inhibits the development of DN in db/db mice. The data suggest that the diminished interstitial fibrosis in these mice is a likely consequence of suppressed EMT like changes. PMID- 28992057 TI - Ca2+/calmodulin-dependent protein kinase II promotes neurodegeneration caused by tau phosphorylated at Ser262/356 in a transgenic Drosophila model of tauopathy. AB - Abnormal deposition of the microtubule-associated protein tau is a common pathological feature of multiple neurodegenerative diseases, including Alzheimer's disease (AD), and plays critical roles in their pathogenesis. Disruption of calcium homeostasis and the downstream kinase Ca2+/calmodulin dependent protein kinase II (CaMKII) coincides with pathological phosphorylation of tau in AD brains. However, it remains unclear whether and how dysregulation of CaMKII affects tau toxicity. Using a Drosophila model, we found that CaMKII promotes neurodegeneration caused by tau phosphorylated at the AD-associated sites Ser262/356. Overexpression of CaMKII promoted, while RNA-mediated knockdown of CaMKII and inhibition of CaMKII activity by expression of an inhibitory peptide suppressed, tau-mediated neurodegeneration. Blocking tau phosphorylation at Ser262/356 by alanine substitutions suppressed promotion of tau toxicity by CaMKII, suggesting that tau phosphorylation at these sites is required for this phenomenon. However, neither knockdown nor overexpression of CaMKII affected tau phosphorylation levels at Ser262/356, suggesting that CaMKII is not directly involved in tau phosphorylation at Ser262/356 in this model. These results suggest that a pathological cascade of events, including elevated levels of tau phosphorylated at Ser262/356 and aberrant activation of CaMKII, work in concert to promote tau-mediated neurodegeneration. PMID- 28992061 TI - GLP inhibits heterochromatin clustering and myogenic differentiation by repressing MeCP2. AB - Myogenic differentiation is accompanied by alterations in the chromatin states, which permit or restrict the transcriptional machinery and thus impact distinctive gene expression profiles. The mechanisms by which higher-order chromatin remodeling is associated with gene activation and silencing during differentiation is not fully understood. In this study, we provide evidence that the euchromatic lysine methyltransferase GLP regulates heterochromatin organization and myogenic differentiation. Interestingly, GLP represses expression of the methyl-binding protein MeCP2 that induces heterochromatin clustering during differentiation. Consequently, MeCP2 and HP1gamma localization at major satellites are altered upon modulation of GLP expression. In GLP knockdown cells, depletion of MeCP2 restored both chromatin organization and myogenic differentiation. These results identify a novel regulatory axis between a histone methylation writer and DNA methylation reader, which is important for heterochromatin organization during differentiation. PMID- 28992062 TI - Epidemiology of human dermatophytoses in Africa. AB - In this critical literature review, we summarize the epidemiological trends of dermatophytoses reported in Africa. Our findings clearly emphasize the heavy burden of dermatophytosis in Africa. Tinea capitis is the primary clinical presentation of dermatophytosis in African children throughout the entire African continent. The disease affects more than 20% of school-age children in West Africa, while the prevalence ranges from 10% to more than 70% in other regions of Africa. In African adults, the presence of tinea corporis is the most frequent indicator of dermatophytosis. However, epidemiological studies have been primarily conducted on particular patient groups that are not representative of the general population. We examined dermatophyte species distribution patterns. We observed a predominance of anthropophilic dermatophytes, mainly T. violaceum, in the North and East of Africa and both T. soudanense and M. audouinii in the Western and Central regions of the continent. Interestingly, the zoophilic species, M. canis, has recently emerged in North and East Africa. Optimization of both mycology diagnosis capacities and epidemiological methodology would provide insight into the role that climate and other global aspects of the human environment play in dermatophyte epidemiology. We advocate that using a multisectoral and collaborative strategy would strengthen such future studies. PMID- 28992063 TI - The evolutionary history of Saccharomyces species inferred from completed mitochondrial genomes and revision in the 'yeast mitochondrial genetic code'. AB - The yeast Saccharomyces are widely used to test ecological and evolutionary hypotheses. A large number of nuclear genomic DNA sequences are available, but mitochondrial genomic data are insufficient. We completed mitochondrial DNA (mtDNA) sequencing from Illumina MiSeq reads for all Saccharomyces species. All are circularly mapped molecules decreasing in size with phylogenetic distance from Saccharomyces cerevisiae but with similar gene content including regulatory and selfish elements like origins of replication, introns, free-standing open reading frames or GC clusters. Their most profound feature is species-specific alteration in gene order. The genetic code slightly differs from well-established yeast mitochondrial code as GUG is used rarely as the translation start and CGA and CGC code for arginine. The multilocus phylogeny, inferred from mtDNA, does not correlate with the trees derived from nuclear genes. mtDNA data demonstrate that Saccharomyces cariocanus should be assigned as a separate species and Saccharomyces bayanus CBS 380T should not be considered as a distinct species due to mtDNA nearly identical to Saccharomyces uvarum mtDNA. Apparently, comparison of mtDNAs should not be neglected in genomic studies as it is an important tool to understand the origin and evolutionary history of some yeast species. PMID- 28992065 TI - The longer the better: follow-up in seemingly 'benign' immunoglobulin A nephropathy. PMID- 28992064 TI - Estimating the Comparative Effectiveness of Feeding Interventions in the Pediatric Intensive Care Unit: A Demonstration of Longitudinal Targeted Maximum Likelihood Estimation. AB - Longitudinal data sources offer new opportunities for the evaluation of sequential interventions. To adjust for time-dependent confounding in these settings, longitudinal targeted maximum likelihood based estimation (TMLE), a doubly robust method that can be coupled with machine learning, has been proposed. This paper provides a tutorial in applying longitudinal TMLE, in contrast to inverse probability of treatment weighting and g-computation based on iterative conditional expectations. We apply these methods to estimate the causal effect of nutritional interventions on clinical outcomes among critically ill children in a United Kingdom study (Control of Hyperglycemia in Paediatric Intensive Care, 2008-2011). We estimate the probability of a child's being discharged alive from the pediatric intensive care unit by a given day, under a range of static and dynamic feeding regimes. We find that before adjustment, patients who follow the static regime "never feed" are discharged by the end of the fifth day with a probability of 0.88 (95% confidence interval: 0.87, 0.90), while for the patients who follow the regime "feed from day 3," the probability of discharge is 0.64 (95% confidence interval: 0.62, 0.66). After adjustment for time-dependent confounding, most of this difference disappears, and the statistical methods produce similar results. TMLE offers a flexible estimation approach; hence, we provide practical guidance on implementation to encourage its wider use. PMID- 28992066 TI - TFIIA transcriptional activity is controlled by a 'cleave-and-run' Exportin 1/Taspase 1-switch. AB - Transcription factor TFIIA is controlled by complex regulatory networks including proteolysis by the protease Taspase 1, though the full impact of cleavage remains elusive. Here, we demonstrate that in contrast to the general assumption, de novo produced TFIIA is rapidly confined to the cytoplasm via an evolutionary conserved nuclear export signal (NES, amino acids 21VINDVRDIFL30), interacting with the nuclear export receptor Exportin-1/chromosomal region maintenance 1 (Crm1). Chemical export inhibition or genetic inactivation of the NES not only promotes TFIIA's nuclear localization but also affects its transcriptional activity. Notably, Taspase 1 processing promotes TFIIA's nuclear accumulation by NES masking, and modulates its transcriptional activity. Moreover, TFIIA complex formation with the TATA box binding protein (TBP) is cooperatively enhanced by inhibition of proteolysis and nuclear export, leading to an increase of the cell cycle inhibitor p16INK, which is counteracted by prevention of TBP binding. We here identified a novel mechanism how proteolysis and nuclear transport cooperatively fine-tune transcriptional programs. PMID- 28992067 TI - The uremic toxin indoxyl sulfate interferes with iron metabolism by regulating hepcidin in chronic kidney disease. AB - Background: Hepcidin secreted by hepatocytes is a key regulator of iron metabolism throughout the body. Hepcidin concentrations are increased in chronic kidney disease (CKD), contributing to abnormalities in iron metabolism. Levels of indoxyl sulfate (IS), a uremic toxin, are also elevated in CKD. However, the effect of IS accumulation on iron metabolism remains unclear. Methods: We used HepG2 cells to determine the mechanism by which IS regulates hepcidin concentrations. We also used a mouse model of adenine-induced CKD. The CKD mice were divided into two groups: one was treated using AST-120 and the other received no treatment. We examined control mice, CKD mice, CKD mice treated using AST-120 and mice treated with IS via drinking water. Results: In the in vitro experiments using HepG2 cells, IS increased hepcidin expression in a dose dependent manner. Silencing of the aryl hydrocarbon receptor (AhR) inhibited IS induced hepcidin expression. Furthermore, IS induced oxidative stress and antioxidant drugs diminished IS-induced hepcidin expression. Adenine-induced CKD mice demonstrated an increase in hepcidin concentrations; this increase was reduced by AST-120, an oral adsorbent of the uremic toxin. CKD mice showed renal anemia, decreased plasma iron concentration, increased plasma ferritin and increased iron content in the spleen. Ferroportin was decreased in the duodenum and increased in the spleen. These changes were ameliorated by AST-120 treatment. Mice treated by direct IS administration showed hepatic hepcidin upregulation. Conclusions: IS affects iron metabolism in CKD by participating in hepcidin regulation via pathways that depend on AhR and oxidative stress. PMID- 28992068 TI - Cost-Benefit Analysis of a Chlamydia trachomatis Vaccine Program in Adolescent Girls in the United States. AB - Background: With >1.4 million cases in the United States reported to the Centers for Disease Control and Prevention in 2012, Chlamydia trachomatis infection is a major public health concern. We examined the impact of a C trachomatis vaccination program using a decision-analysis model to estimate the effects of vaccination on C trachomatis-associated costs and morbidity. Methods: We developed a Markov model considering a cohort of 2158117 US females aged 9 to 26 years. Morbidity, death, and healthcare-associated costs associated with chlamydial infection of mothers and fetuses/neonates were calculated over a 17 year time frame. We developed 2 major comparison arms, namely, a C trachomatis vaccination program and no C trachomatis vaccination program. Base-case efficacy and coverage were set to those of human papillomavirus in the United States with all variables, including efficacy and coverage, ranged in sensitivity analyses. Results: On the basis of a base-case analysis, a vaccination program would cost an estimated $710 million for a cohort of 2158117 women over a 17-year period, an increase of $41 million over having no vaccination program. A vaccination program would prevent 34000 cases of C trachomatis infection and 5976 cases of pelvic inflammatory disease. Conclusions: A C trachomatis vaccination program results in increased cost to the healthcare system but averts significant morbidity and death. PMID- 28992069 TI - Local delivery of liposomal prednisolone leads to an anti-inflammatory profile in renal ischaemia-reperfusion injury in the rat. AB - Background: Treatment of inflammatory kidney diseases with systemic high-dose glucocorticoids (GCs) has severe side effects. Liposomal encapsulation could facilitate local delivery of GCs to the inflamed kidney, as liposomes encapsulate their payload until extravasation at sites of inflammation, potentially resulting in local bioactivity. Our aim was to evaluate the ability of liposomes to accumulate locally after renal ischaemia-reperfusion injury in the rat and to study its effect on macrophages. Methods: In vitro, human macrophages were incubated with fluorescent liposomes, liposomal prednisolone, prednisolone, empty liposomes or saline. Uptake was studied microscopically and treatment effect was assessed by interkeukin 6 (IL-6) enzyme-linked immunosorbent assay. The mechanism of action was evaluated by analysing GC receptor activation by microscopy and quantitative polymerase chain reaction (qPCR). In vivo, rats were subjected to ischaemia-reperfusion injury and were injected intravenously with fluorescent liposomes, liposomal prednisolone, prednisolone, empty liposomes or saline. Uptake was measured by the FLARE camera and the treatment effect by immunohistochemistry for myeloid cells and qPCR for inflammatory markers. Results: In vitro, macrophages internalized liposomes after 8 hours. Prednisolone or liposomal prednisolone treatment reduced IL-6 production and both compounds induced translocation of the GC receptor to the nucleus and upregulation of PER1 messenger RNA (mRNA), indicating a similar mechanism of action. In vivo, fluorescent liposomes accumulated in the inflamed kidney. Liposomal prednisolone treatment increased the presence of ED2-positive anti-inflammatory macrophages and both prednisolone and liposomal prednisolone reduced monocyte chemoattractant protein-1 (MCP-1) mRNA production, indicating a reduced pro-inflammatory profile in the kidney. Conclusions: Liposomal encapsulation is a promising strategy for local delivery of glucocorticoids to the inflamed kidney. PMID- 28992070 TI - Changing While Staying the Same: Preservation of Structural Continuity During Limb Evolution by Developmental Integration. AB - More than 150 years since Charles Darwin published "On the Origin of Species", gradual evolution by natural selection is still not fully reconciled with the apparent sudden appearance of complex structures, such as the bat wing, with highly derived functions. This is in part because developmental genetics has not yet identified the number and types of mutations that accumulated to drive complex morphological evolution. Here, we consider the experimental manipulations in laboratory model systems that suggest tissue interdependence and mechanical responsiveness during limb development conceptually reduce the genetic complexity required to reshape the structure as a whole. It is an exciting time in the field of evolutionary developmental biology as emerging technical approaches in a variety of non-traditional laboratory species are on the verge of filling the gaps between theory and evidence to resolve this sesquicentennial debate. PMID- 28992071 TI - Prenatal Screening for and Prevalence of Hepatitis B Surface Antigen in Pregnant Women and Prevention of Transmission to Infants Born to Infected Mothers-Guam, 2014. AB - Background: Perinatal transmission is the major mode of hepatitis B virus (HBV) transmission and drives HBV endemicity in the US territory of Guam. We assessed correlates of prenatal hepatitis B surface antigen (HBsAg) screening and HBsAg positivity among pregnant women and evaluated the care of infants of HBsAg positive women. Methods: Demographic and clinical data were abstracted from the maternal medical records of 966 randomly selected live infants born in 2014. Frequencies were calculated, and prevalence ratios (PRs) and 95% confidence intervals (CIs) were estimated using Poisson regression. Results: Among the mothers of the 966 infants, 78.2% were Pacific Islanders, 56.9% were >25 years old (born before universal infant hepatitis B vaccination in Guam), 89.0% received prenatal care (PNC), 96.7% underwent prenatal HBsAg screening, and 2.0% were HBsAg positive. Approximately 15% of the women who did not have PNC were not screened for HBsAg. Receipt of PNC was associated with HBsAg screening (adjusted PR, 1.13 [95% CI, 1.04-1.23]), and HBsAg positivity was associated with a maternal age of >25 years (adjusted PR, 6.80 [95% CI, 1.32-35.08]). All 18 infants of the HBsAg-positive mothers received hepatitis B vaccine, and 17 (94.4%) received hepatitis B immunoglobulin. Conclusion: Although the prenatal HBsAg screening prevalence in this sample was high, the maternal HBsAg prevalence among women in this sample was more than 14 times and 2 times the prevalence among US-born Pacific Islander/Asian women and all women in the continental United States, respectively. Improving access to PNC, ensuring that all pregnant women in Guam (especially those born before universal hepatitis B vaccination) are screened for HBsAg, and adopting postexposure prophylaxis for infants of HBsAg-positive mothers as standard clinical practice are important for preventing perinatal HBV transmission and reducing HBV endemicity. PMID- 28992073 TI - Urinary peptide biomarker panel associated with an improvement in estimated glomerular filtration rate in chronic kidney disease patients. AB - Background: An improvement in the glomerular filtration rate (GFR) of chronic kidney disease patients has been an underestimated clinical outcome. Although this may be considered as an unexpected disease course, it may provide some insights into possible mechanisms underlying disease remission and/or regression. Therefore, our aim was to identify urinary peptide biomarkers associated with an improvement in estimated GFR (eGFR) over time and to improve patient stratification. Methods: Capillary electrophoresis coupled with mass spectrometry (CE-MS) was employed to evaluate the urine peptidome of patients with different types of renal diseases. In total, 376 patients with a slope/year between -1.5% and +1.5% were designated as non-progressors or stable, while 177 patients with a > 5% slope/year were designated as patients with an improved eGFR for state-of art biomarker discovery and validation. Results: We detected 384 significant peptide fragments by comparing the CE-MS data of the stable patients and those with improved renal function in our development cohort. Of these 384, a set of 141 peptides with available amino acid sequence information were used to generate a support vector machine-based classification panel. The biomarker panel was applied to our validation cohort, achieving a moderate area under the curve (AUC) value of 0.85 (81% sensitivity and 81% specificity). The majority of the peptides (78%) from the diagnostic panel arose from different types of collagen. Conclusions: We have developed a panel of urinary peptide markers able to discriminate those patients predisposed to improve their kidney function over time and possibly be treated with more specific or less aggressive therapy. PMID- 28992072 TI - Attention and Motivated Response to Simulated Male Advertisement Call Activates Forebrain Dopaminergic and Social Decision-Making Network Nuclei in Female Midshipman Fish. AB - Little is known regarding the coordination of audition with decision-making and subsequent motor responses that initiate social behavior including mate localization during courtship. Using the midshipman fish model, we tested the hypothesis that the time spent by females attending and responding to the advertisement call is correlated with the activation of a specific subset of catecholaminergic (CA) and social decision-making network (SDM) nuclei underlying auditory- driven sexual motivation. In addition, we quantified the relationship of neural activation between CA and SDM nuclei in all responders with the goal of providing a map of functional connectivity of the circuitry underlying a motivated state responsive to acoustic cues during mate localization. In order to make a baseline qualitative comparison of this functional brain map to unmotivated females, we made a similar correlative comparison of brain activation in females who were unresponsive to the advertisement call playback. Our results support an important role for dopaminergic neurons in the periventricular posterior tuberculum and ventral thalamus, putative A11 and A13 tetrapod homologues, respectively, as well as the posterior parvocellular preoptic area and dorsomedial telencephalon, (laterobasal amygdala homologue) in auditory attention and appetitive sexual behavior in fishes. These findings may also offer insights into the function of these highly conserved nuclei in the context of auditory-driven reproductive social behavior across vertebrates. PMID- 28992074 TI - Auxin-mediated developmental control in the moss Physcomitrella patens. AB - The signalling molecule auxin regulates many fundamental aspects of growth and development in plants. We review and discuss what is known about auxin-regulated development in mosses, with special emphasis on the model species Physcomitrella patens. It is well established that mosses and other early diverging plants produce and respond to auxin. By sequencing the P. patens genome, it became clear that it encodes many core proteins important for auxin homeostasis, perception, and signalling, which have also been identified in flowering plants. This suggests that the auxin molecular network was present in the last common ancestor of flowering plants and mosses. Despite fundamental differences in their life cycles, key processes such as organ initiation and outgrowth, branching, tropic responses, as well as cell differentiation, division, and expansion appear to be regulated by auxin in the two lineages. This knowledge paves the way for studies aimed at a better understanding of the origin and evolution of auxin function and how auxin may have contributed to the evolution of land plants. PMID- 28992075 TI - Does Kidney Donor Risk Index implementation lead to the transplantation of more and higher-quality donor kidneys? AB - Background: The Kidney Donor Risk Index (KDRI) is a quantitative evaluation of the quality of donor organs and is implemented in the US allocation system. This single-centre study investigates whether the implementation of the KDRI in our decision-making process to accept or decline an offered deceased donor kidney, increases our acceptance rate. Methods: From April 2015 until December 2016, we prospectively calculated the KDRI for all deceased donor kidney offers allocated by Eurotransplant to our centre. The number of the transplanted versus declined kidney offers during the study period were compared to a historical set of donor kidney offers. Results: After implementation of the KDRI, 26.1% (75/288) of all offered donor kidneys were transplanted, compared with 20.7% (136/657) in the previous period (P < 0.001). The median KDRI of all transplanted donor kidneys during the second period was 0.97 [Kidney Donor Profile Index (KDPI) 47%], a value significantly higher than the median KDRI of 0.85 (KDPI 34%) during the first period (P = 0.047). A total of 68% of patients for whom a first-offered donor kidney was declined during this period were transplanted after a median waiting time of 386 days, mostly with a lower KDRI donor kidney. Conclusions: Implementing the KDRI in our decision-making process increased the transplantation rate by 26%. The KDRI can be a supportive tool when considering whether to accept or decline a deceased donor kidney offer. More data are needed to validate this score in other European centres. PMID- 28992077 TI - Merging roads: chemical tools and cell biology to study unconventional protein secretion. AB - The endomembrane trafficking network is highly complex and dynamic, with both conventional and so-called unconventional routes which are in essence recently discovered pathways that are poorly understood in plants. One approach to dissecting endomembrane pathways that we have pioneered is the use of chemical biology. Classical genetic manipulations often deal with indirect pleiotropic phenotypes resulting from the perturbation of key players of the trafficking routes. Many of these difficulties can be circumvented using small molecules to modify or disrupt the function or localization of key proteins regulating these pathways. In this review, we summarize how small molecules have been used as probes to define these pathways, and how they could be used to increase current knowledge of unconventional protein secretion pathways. PMID- 28992076 TI - Autoimmunity associated with chemically induced thymic dysplasia. AB - Autoimmune and inflammatory conditions are frequent complications in patients with reduced numbers of T cells. Here, we describe a mouse model of thymic stromal dysplasia resulting in peripheral T-cell lymphopenia. In Foxn1:CFP-NTR transgenic mice, the bacterial nitroreductase enzyme is expressed in thymic epithelial cells and converts the prodrug CB1954 into a cytotoxic agent. This strategy enables titratable and durable destruction of thymopoietic tissue in early embryogenesis. Our results indicate that the resulting low levels of thymic capacity for T-cell production create a predisposition for the development of a complex autoimmune syndrome, chiefly characterized by inflammatory bowel disease and lymphocytic organ infiltrations. We conclude that the Foxn1:CFP-NTR transgenic mouse strain represents a suitable animal model to optimize established clinical protocols, such as thymus transplantation, to correct various forms of thymic dysplasia and to explore novel treatment options. PMID- 28992078 TI - Auxin transport, metabolism, and signalling during nodule initiation: indeterminate and determinate nodules. AB - Most legumes can form a unique type of lateral organ on their roots: root nodules. These structures host symbiotic nitrogen-fixing bacteria called rhizobia. Several different types of nodules can be found in nature, but the two best-studied types are called indeterminate and determinate nodules. These two types differ with respect to the presence or absence of a persistent nodule meristem, which consistently correlates with the cortical cell layers giving rise to the nodule primordia. Similar to other plant developmental processes, auxin signalling overlaps with the site of organ initiation and meristem activity. Here, we review how auxin contributes to early nodule development. We focus on changes in auxin transport, signalling, and metabolism during nodule initiation, describing both experimental evidence and computer modelling. We discuss how indeterminate and determinate nodules may differ in their mechanisms for generating localized auxin response maxima and highlight outstanding questions for future research. PMID- 28992080 TI - Naphthylphthalamic acid and the mechanism of polar auxin transport. AB - Our current understanding of how plants move auxin through their tissues is largely built on the use of polar auxin transporter inhibitors. Although the most important proteins that mediate auxin transport and its regulation have probably all been identified and the mapping of their interactions is well underway, mechanistically we are still surprisingly far away from understanding how auxin is transported. Such an understanding will only emerge after new data are placed in the context of the wealth of physiological data on which they are founded. This review will look back over the use of a key inhibitor called naphthylphthalamic acid (NPA) and outline its contribution to our understanding of the molecular mechanisms of polar auxin transport, before proceeding to speculate on how its use is likely still to be informative. PMID- 28992079 TI - Sustained activation of P2X7 induces MMP-2-evoked cleavage and functional purinoceptor inhibition. AB - P2X7 purinoceptor promotes survival or cytotoxicity depending on extracellular adenosine triphosphate (ATP) stimulus intensity controlling its ion channel or P2X7-dependent large pore (LP) functions. Mechanisms governing this operational divergence and functional idiosyncrasy are ill-understood. We have discovered a feedback loop where sustained activation of P2X7 triggers release of active matrix metalloproteinase 2 (MMP-2), which halts ion channel and LP responses via the MMP-2-dependent receptor cleavage. This mechanism operates in cells as diverse as macrophages, dystrophic myoblasts, P2X7-transfected HEK293, and human tumour cells. Given that serum-born MMP-2 activity also blocked receptor functions, P2X7 responses in vivo may decrease in organs with permeable capillaries. Therefore, this mechanism represents an important fine-tuning of P2X7 functions, reliant on both cell-autonomous and extraneous factors. Indeed, it allowed evasion from the ATP-induced cytotoxicity in macrophages and human cancer cells with high P2X7 expression levels. Finally, we demonstrate that P2X7 ablation eliminated gelatinase activity in inflamed dystrophic muscles in vivo. Thus, P2X7 antagonists could be used as an alternative to highly toxic MMP inhibitors in treatments of inflammatory diseases and cancers. PMID- 28992081 TI - Apical secretion of Wnt1 in polarized epithelial cells is regulated by exocyst mediated trafficking. AB - Wnts are glycosylated proteins secreted from various cell types including mesenchymal, hematopoietic and epithelial cells. Directional secretion of Wnts in polarized epithelial cells is unique; Wnt11 is secreted apically, whereas Wnt5a and Wnt3a are secreted basolaterally. Here, we found that Wnt1 is equivalently secreted both apically and basolaterally in MDCK cells. Wnt1 was modified with a complex- or hybrid-type glycan at Asn29 and Asn359 and the high-mannose- or hybrid-type glycan at Asn316. Although glycosylation of Wnt11 at the N-terminal site was shown to be essential for its apical secretion, glycosylation of Asn29 of Wnt1 was not required. Instead, the apical secretion of Wnt1 was inhibited by knockdown of Sec6 and Sec8, suggesting that Wnt1 is secreted apically via exocyst mediated transport. Basolateral secretion of Wnt1 was mediated by clathrin and AP 1, in mechanism similar to that used by Wnt5a and Wnt3a. Although Wingless was reported to be transcytosed to the basolateral region in the Drosophila wing disc, transcytosis was not involved in the basolateral secretion of Wnt1. Thus, the polarized secretion of Wnt1 is regulated by different mechanisms than other Wnts. PMID- 28992082 TI - Frequency of micronuclei among persons resident in the vicinity of a mineral sand processing factory in Pulmoddai, Sri Lanka. AB - Lanka Mineral Sands Ltd (LMS), a government-owned company, has been mining mineral sands including monazite which contains thorium (Th) at Pulmoddai, Sri Lanka since 1957. Th emits alpha particles on decay and gamma rays are emitted by the daughter products. The cytokinesis-blocked micronucleus (MN) assay is popular for large scale radiation exposure studies as it is an easy, fast and reliable method of biodosimetry. The objective of the study was to determine the frequency of micronuclei among persons residing in the vicinity of LMS. A cross-sectional study was conducted from November 2012 to September 2016 among persons 35-45 years of age to evaluate the frequency of micronuclei in peripheral blood lymphocytes. Fifty-three employees of LMS factory, 25 residents within 5 km from LMS, 25 residents 20-25 km from LMS and 29 residents from >50 km away from LMS were included in the study. The highest median frequency of micronuclei per 1000 binucleated (BN) cells was in the group residing within 5 km from LMS with a median (IQ range) of 0.67 (0.17-2.17). The median (IQ range) of MN frequency of employees of LMS, residents 20-25 km from LMS and residents >50 km from LMS were 0.66 (0.16-1.16), 0.33 (0.00-0.67) and 0.33 (0.33-0.67), respectively. There was no significant difference in the MN frequency between employees of LMS and the group residing within 5 km from LMS. Being a resident of Pulmoddai and being exposed to X-rays were significant predictors of MN frequency. Persons residing within 5 km from LMS had a higher risk of MN formation irrespective of being employed at LMS. PMID- 28992083 TI - Cryptococcal Meningoencephalitis Complicated by Subdural Empyema in an 8-Year-Old Girl With Neonatal-Onset Multisystem Inflammatory Disease Syndrome: A Rare Sequela. PMID- 28992084 TI - AMPK regulates anaphase central spindle length by phosphorylation of KIF4A. AB - AMP-activated protein kinase (AMPK) is an energy sensor that couples the cellular energy state with basic biological processes. AMPK is thought to be linked with cell division although the underlying mechanisms remain largely unknown. Here, we show that AMPK functionally participates throughout cell division and that AMPK catalytic subunits, especially alpha2, are sequentially associated with separate mitotic apparatus. Using quantitative phosphoproteomics analysis, we found that the strong direct substrate KIF4A is phosphorylated by AMPK at Ser801. Further analysis revealed that AMPK and Aurora B competitively phosphoregulates KIF4A during mitotic phase due to overlapping recognition motifs, resulting in the elaborate phosphoregulation for KIF4A-dependent central spindle length control. Given the intrinsic energy-sensing function of AMPK, our study links the KIF4A dependent control of central spindle length with cellular glucose stress. PMID- 28992085 TI - Assessment of DNA damage in ceramic workers. AB - It is known that ceramic workers are potentially exposed to complex mixture of chemicals such as silica, inorganic lead, lime, beryllium and aluminum that can be associated with an increased risk of several diseases. All operations in the ceramic industries such as mixing, moulding, casting, shaking out and finishing jobs, have been associated with the higher exposure levels and in most of the silica-related industries, average overall exposure exceeded permissible exposure levels for respirable crystalline silica. The aim of this study was to evaluate the possible genotoxic damage in ceramic workers exposed to complex mixture of chemicals mainly crystalline silica. For this purpose, the blood and buccal epithelial cell samples were taken from the ceramic workers (n = 99) and their controls (n = 81). The genotoxicity was assessed by the alkaline comet assay in isolated lymphocytes and whole blood. Micronucleus (MN), binucleated (BN), pyknotic (PYC), condensed chromatin (CC), karyolytic (KYL), karyorrhectic (KHC) and nuclear bud (NBUD) frequencies in buccal epithelial cells and plasma 8-oxo 7,8-dihydro-2'-deoxyguanosine (8-oxodG) levels were also evaluated. In the study, 38 workers were diagnosed with silicosis, 9 workers were suspected to have silicosis, whereas 52 workers were found to be healthy. DNA damage in blood and lymphocytes; MN, CC + KHC, PYC frequencies in buccal epithelial cells and 8-oxodG levels in plasma were increased in workers compared to their controls. These results showed that occupational chemical mixture exposure in ceramic industry may cause genotoxic damage that can lead to important health problems in the workers. PMID- 28992087 TI - Fine-tuning timing: natural variation informs the mechanistic basis of the switch to flowering in Arabidopsis thaliana. AB - The evolution of diverse life history strategies has allowed Arabidopsis thaliana to adapt to worldwide locations, spanning a range of latitudinal and environmental conditions. Arabidopsis thaliana accessions are either vernalization-requiring winter annuals or rapid cyclers, with extensive natural variation in vernalization requirement and response. Genetic and molecular analysis of this variation has enhanced our understanding of the mechanisms involved in life history determination, with translation to both natural and crop systems in the Brassicaceae and beyond. PMID- 28992086 TI - Measured (and estimated) glomerular filtration rate: reference values in West Africa. AB - Background: Establishment of normal reference values for glomerular filtration rate (GFR) is mandatory in nephrology. However, no data are available for measured GFR (mGFR) in Africa. Methods: GFR was measured in 237 healthy adult subjects (103 women and 134 men, mean age 34 +/- 10 years) by iohexol plasma clearance. Results: The mean mGFR was 103 +/- 17 mL/min/1.73 m2 and the median value was 103 mL/min/1.73 m2 (2.5th and 97.5th percentiles are 76 and 137 mL/min/1.73 m2, respectively). No significant difference in mGFR results was observed in patients < 40 years of age, whereas a significant decline in mGFR was observed after 40 years of age. There was no significant difference between mGFR in men and women. Conclusions: Normal GFR values and descriptions of percentiles are now available for West Africa. As in Caucasians, no significant difference was observed between men and women. Moreover, the same age-associated decline in mGFR is also observed after 40 years of age, as in Caucasians. PMID- 28992088 TI - Carbon-ion radiotherapy for patients with advanced stage non-small-cell lung cancer at multicenters. AB - Carbon-ion radiation therapy (CIRT) for advanced non-small-cell lung cancer (NSCLC) has not been well studied to date. This paper aimed to analyze a retrospective multicenter survey for detecting problems with the use of CIRT for Stage II and III NSCLC (7th UICC TNM Staging System). Inclusion was restricted to patients with Stage II and III NSCLC who received CIRT from November 2003 to December 2014. We gathered the data from three CIRT operating centers on July 2015. Patients with radiotherapy history, patients with cancers other than lung cancer, and those receiving palliative therapies were excluded. The patient characteristics, prescribed dose/fraction, survival rates, and adverse effects were analyzed. The total number of patients was 64 (male: 49, female: 15). Of these, 53 patients were medically inoperable. The median age was 76 years (range 46-91), and the median follow-up period was 18.5 months (range 3.2-121.5). The clinical staging consisted of 10 Stage IIA, 30 Stage IIB, 23 Stage IIIA and 1 Stage IIIB. The median prescribed dose was 72.0 Gy (RBE) (range 52.8-72.0) in 16 fractions (range 4-16). The 2-year overall survival, progression-free survival, and local control rates were 62.2% [confidence interval (CI): 47.5-76.9], 42.3% (CI: 28.8-55.8) and 81.8% (CI: 69.9-94.0), respectively. There were no higher than Grade 2 adverse effects observed. CIRT for inoperable Stage II and III NSCLC could be implemented without severe adverse effects, but the clinical staging (including lymph node status) was inhomogeneous. In addition, the prescribed dose and fractionation were not standardized. Further data accumulation and a multiple centers prospective trial for evaluating clinical stage-based results are required. PMID- 28992089 TI - p-Cresyl glucuronide is a major metabolite of p-cresol in mouse: in contrast to p cresyl sulphate, p-cresyl glucuronide fails to promote insulin resistance. AB - Background: The role of uraemic toxins in insulin resistance associated with chronic kidney disease (CKD) is gaining interest. p-Cresol has been defined as the intestinally generated precursor of the prototype protein-bound uraemic toxins p-cresyl sulphate (p-CS) as the main metabolite and, at a markedly lower concentration in humans, p-cresyl glucuronide (p-CG). The objective of the present study was to evaluate the metabolism of p-cresol in mice and to decipher the potential role of both conjugates of p-cresol on glucose metabolism. Methods: p-CS and p-CG were measured by high performance liquid chromatography fluorescence in serum from control, 5/6 nephrectomized mice and mice injected intraperitoneously with either p-cresol or p-CG. The insulin sensitivity in vivo was estimated by insulin tolerance test. The insulin pathway in the presence of p cresol, p-CG and/or p-CS was further evaluated in vitro on C2C12 muscle cells by measuring insulin-stimulated glucose uptake and the insulin signalling pathway (protein kinase B, PKB/Akt) by western blot. Results: In contrast to in humans, where p-CS is the main metabolite of p-cresol, in CKD mice both conjugates accumulated, and after chronic p-cresol administration with equivalent concentrations but a substantial difference in protein binding (96% for p-CS and <6% for p-CG). p-CG exhibited no effect on insulin sensitivity in vivo or in vitro and no synergistic inhibiting effect in combination with p-CS. Conclusions: The relative proportion of the two p-cresol conjugates, i.e. p-CS and p-CG, is similar in mouse, in contrast to humans, pinpointing major inter-species differences in endogenous metabolism. Biologically, the sulpho- (i.e. p-CS) but not the glucuro- (i.e. p-CG) conjugate promotes insulin resistance in CKD. PMID- 28992090 TI - Mechanical properties of cuticles and their primary determinants. AB - Cuticles envelope primary surfaces of the above-ground portion of plants. They function as barriers to water movement and to gas exchange, and in pathogen defense. To serve as a barrier on growing organs, cuticles must remain intact but at the same time must accommodate ongoing growth. Minimizing cuticle failure has stimulated significant research on the cuticle's mechanical properties. The objective here is to review the literature on the mechanical properties of isolated fruit and leaf cuticles. Cuticles are viscoelastic polymers. Viscoelasticity results mainly from the cutin matrix. Impregnation by waxes, flavonoids, and cutan increases stiffness and strength but decreases extensibility. On the inner side, the cutin matrix is impregnated by cell wall polysaccharides, which are responsible for its elastic behavior. Across species, the maximum forces sustainable by hydrated cuticles in uniaxial tensile tests averaged 0.82 N (range 0.15-1.63 N), the maximum stresses averaged 13.2 MPa (range 2.0-29.0 MPa), the maximum strains averaged 8.8% (range 1.6-28.0%), and the moduli of elasticity averaged 224 MPa (range 60-730 MPa). Among the environmental factors, high temperature and hydration both decreased stiffness. Therefore, the mechanical properties of cuticles in vivo depend largely on the relative proportions of their constituents. These proportions change during development and are also affected by environmental factors such as temperature. PMID- 28992092 TI - The influence of exogenous metabolism on the specificity of in vitro mammalian genotoxicity tests. AB - A two-part study was designed to determine whether the inclusion of the rodent liver 'S9' exogenous metabolic activating system contributes to the generation of misleading positive results by the regulator-required in vitro mammalian genotoxicity tests. The mono-oxygenase enzymes in S9 produce direct-acting DNA reactive electrophiles, and are included in in vitro genotoxicity tests to enhance the detection of substances which only become genotoxic following metabolism. However, as the S9 system lacks 'detoxifying' phase 2 factors it was hypothesised that increased chemical metabolism per se may lead to an increase in irrelevant S9 test outcomes in safety assessment. To test this, 89 compounds with positive or negative carcinogenicity data were identified, which produced negative Ames test data (+/- S9), and only produced positive in vitro mammalian test data in the presence of S9. This allowed a determination of whether or not misleading predictions of carcinogenicity by the in vitro mammalian tests were more or less prevalent in the presence of S9. A subset of these compounds was then tested with and without S9 in the GADD45a-GFP genotoxicity test, in order to determine whether misleading in vitro mammalian positive results were generally more prevalent with S9, or reflected particular tests' liabilities. This study suggests that the use of S9 metabolic activation in in vitro genotoxicity tests does not increase the prevalence of misleading positive results in in vitro mammalian genotoxicity assays, at least amongst Ames negative compounds. PMID- 28992091 TI - Roles for IBA-derived auxin in plant development. AB - The plant hormone auxin is a central regulator of plant growth and development. Because auxin plays critical roles in cell division and cell expansion, plants use a number of cellular mechanisms to regulate auxin levels and response. Among these mechanisms is regulated input from the auxin precursor indole-3-butyric acid (IBA) toward the pool of active auxin [indole-3-acetic acid (IAA)]. In this review, we cover the mechanisms of IBA transport and conversion, and discuss specific roles for IBA-derived auxin in driving certain developmental events. We further discuss multiple open questions remaining for the IBA field. PMID- 28992093 TI - Voriconazole treatment in adults and children with hematological diseases: can it be used without measurement of plasma concentration? AB - Indication and timing of trough plasma-voriconazole (VCZ)-concentration (t-PVC) measurement during VCZ treatment is a debated issue. Patterns of t-PVC were prospectively evaluated in pediatric (50 courses) and adult (95 courses) hematologic patients. Efficacy patterns were defined: adequate, t-PVC always >=1 mcg/ml; borderline, at least one t-PVC measurement <1 mcg/ml but median value of the measurements >=1 mcg/ml; inadequate, median value of the measurements <1 mcg/ml. Toxicity patterns were defined: favorable, t-PVC always <=5 mcg/ml; borderline, one or more t-PVC measurements >5 mcg/ml but median value of the measurements <=5 mcg/ml; unfavorable, median value of the measurements >5 mcg/ml. In children and adults the mean t-PVCs were higher during intravenous treatments. The t-PVC efficacy pattern was adequate, borderline and inadequate in 48%, 12%, and 40% of courses, respectively, in children, and in 66.3%, 16.8%, and 16.8% of courses, respectively, in adults. Adequate efficacy pattern was more frequent in children with body weight above the median (>=25 kg) (OR 4.8; P = .011) and in adults with active hematological disease receiving intravenous therapy (OR 3.93; P = .006). Favorable toxicity pattern was more frequent in children receiving VCZ daily dosage below the median (<14 mg/kg) (OR 4.18; P = .027) and in adults with body weight below the median (<68 kg) (OR 0.22; P = .004). T-PVC measurement is generally needed, however, a non t-PVC guided approach may be considered in heavier adults receiving intravenous VCZ. The risk of supratherapeutic levels does not seem an absolute indication for t-PVC monitoring. PMID- 28992094 TI - Association between conversion to in-center nocturnal hemodialysis and right ventricular remodeling. AB - Background: In-center nocturnal hemodialysis (INHD) is associated with favorable left ventricular (LV) remodeling. Although right ventricular (RV) structure and function carry prognostic significance, the impact of dialysis intensification on RV is unknown. Our objectives were to evaluate changes in RV mass index (MI), end diastolic volume index (EDVI), end-systolic volume index (ESVI) and ejection fraction (EF) after conversion to INHD and their relationship with LV remodeling. Methods: Of 67 conventional hemodialysis (CHD, 4 h/session, three times/week) patients, 30 continued on CHD and 37 converted to INHD (7-8 h/session, three times/week). Cardiac magnetic resonance imaging was performed at baseline and 1 year using a standardized protocol; an experienced and blinded reader performed RV measurements. Results: At 1 year there were significant reductions in RVMI { 2.1 g/m2 [95% confidence interval (CI) -3.8 to - 0.4], P = 0.017}, RVEDVI [-9.5 mL/m2 (95% CI - 16.3 to - 2.6), P = 0.008] and RVESVI [-6.2 mL/m2 (95% CI - 10.9 to - 1.6), P = 0.011] in the INHD group; no significant changes were observed in the CHD group. Between-group comparisons showed significantly greater reduction of RVESVI [-7.9 mL/m2 (95% CI - 14.9 to - 0.9), P = 0.03] in the INHD group, a nonsignificant trend toward greater reduction in RVEDVI and no significant difference in RVMI and RVEF changes. There was significant correlation between LV and RV in terms of changes in mass index (MI) (r = 0.46), EDVI (r = 0.73), ESVI (r = 0.7) and EF (r = 0.38) over 1 year (all P < 0.01). Conclusions: Conversion to INHD was associated with a significant reduction of RVESVI. Temporal changes in RV mass, volume and function paralleled those of LV. Our findings support the need for larger, longer-term studies to confirm favorable RV remodeling and determine its impact on clinical outcomes. PMID- 28992095 TI - The reduction of heparan sulphate in the glomerular basement membrane does not augment urinary albumin excretion. AB - Background: Heparan sulphate proteoglycan (HSPG) is present in the glomerular basement membrane (GBM) and is thought to play a major role in the glomerular charge barrier. Reductions and structural alterations of HSPG are observed in different types of kidney diseases accompanied by proteinuria. However, their causal relations remain unknown. Methods: We generated podocyte-specific exostosin-like 3 gene (Extl3) knockout mice (Extl3KO) using a Cre-loxP recombination approach. A reduction of HSPG was expected in the GBM of these mice, because EXTL3 is involved in its synthesis. Mice were separated into three groups, according to the loads on the glomeruli: a high-protein diet group, a high-protein and high-sodium diet group and a hyperglycaemic group induced by streptozotocin treatment in addition to maintenance on a high-protein and high sodium diet. The urinary albumin:creatinine ratio was measured at 7, 11, 15 and 19 weeks of age. Renal histology was also investigated. Results: Podocyte specific expression of Cre recombinase was detected by immunohistochemistry. Moreover, immunofluorescent staining demonstrated a significant reduction of HSPG in the GBM. Electron microscopy showed irregularities in the GBM and effacement of the foot processes in Extl3KO. The values of the urinary albumin:creatinine ratio were within the range of microalbuminuria in all groups and did not significantly differ between the control mice and Extl3KO. Conclusions: The reduction of HSPG in the GBM did not augment urinary albumin excretion. HSPG's anionic charge appears to contribute little to the glomerular charge barrier. PMID- 28992096 TI - Evaluating the Population Impact on Racial/Ethnic Disparities in HIV in Adulthood of Intervening on Specific Targets: A Conceptual and Methodological Framework. AB - Reducing racial/ethnic disparities in human immunodeficiency virus (HIV) disease is a high priority. Reductions in HIV racial/ethnic disparities can potentially be achieved by intervening on important intermediate factors. The potential population impact of intervening on intermediates can be evaluated using observational data when certain conditions are met. However, using standard stratification-based approaches commonly employed in the observational HIV literature to estimate the potential population impact in this setting may yield results that do not accurately estimate quantities of interest. Here we describe a useful conceptual and methodological framework for using observational data to appropriately evaluate the impact on HIV racial/ethnic disparities of interventions. This framework reframes relevant scientific questions in terms of a controlled direct effect and estimates a corresponding proportion eliminated. We review methods and conditions sufficient for accurate estimation within the proposed framework. We use the framework to analyze data on 2,329 participants in the CFAR [Centers for AIDS Research] Network of Integrated Clinical Systems (2008 2014) to evaluate the potential impact of universal prescription of and >=95% adherence to antiretroviral therapy on racial disparities in HIV virological suppression. We encourage the use of the described framework to appropriately evaluate the potential impact of targeted interventions in addressing HIV racial/ethnic disparities using observational data. PMID- 28992097 TI - Association of serum albumin levels with kidney function decline and incident chronic kidney disease in elders. AB - Background: Previous studies in HIV-infected individuals have demonstrated serum albumin to be strongly associated with kidney function decline, independent of urine albumin and inflammatory markers. Lower serum albumin concentrations may be an under-appreciated risk factor for kidney function decline in elders. Methods: We performed a cohort analysis in the Health Aging and Body Composition Study, a cohort of well-functioning, bi-racial, community-dwelling elders between the age of 70 and 79 years. We examined the associations of serum albumin concentration with longitudinal kidney function decline by estimated glomerular filtration rate (eGFR). Outcomes included linear eGFR decline, rapid kidney function decline defined as >30% decrease in eGFR, defined as a final eGFR <60 mL/min/1.73 m2 in those with an eGFR >60 mL/min/1.73 m2 at baseline. Cystatin C-based eGFR was calculated at baseline, Year 3 and Year 10. Results: Mean age was 74 years, and mean eGFR was 73 mL/min/1.73 m2 at baseline. The mean rate of eGFR change was 1.81 mL/min/1.73 m2 per year. After multivariate adjustment, lower serum albumin concentrations were strongly and independently associated with kidney function decline (-0.11 mL/min/1.73 m2 per year for each standard deviation decrease serum albumin; -0.01 to - 0.20) with no attenuation after adjustment for urine albumin and inflammatory markers (-0.12, -0.03 to - 0.22). When divided into quartiles, serum albumin levels <=3.80 g/dL were associated with increased odds of rapid kidney function decline (odds ratio 1.59; 1.12-2.26) and increased risk of incident chronic kidney disease (incident rate ratio 1.29; 1.03-1.62) relative to levels >4.21g/dL. Urine albumin to creatinine ratio (ACR) was also significantly and independently associated with kidney function decline (-0.08 mL/min/1.73 m2 per year for urine ACR >30 mg/g; -0.82 to - 0.13). Conclusions: Lower serum albumin levels are strongly and independently associated with kidney function decline in elders, independent of clinical risk factors, urine albumin and measured inflammatory markers. PMID- 28992098 TI - With a Little Help from My Friends: Microbial Partners in Integrative and Comparative Biology-An Introduction to the Symposium. AB - The role that host-associated microbes play in animal biology is gaining attention in comparative biology. Numerous research groups study the roles that microbes play in human health and nutrition, or in enhancing the production of agricultural animals. However, inclusion of host-associated microbes into research questions of integrative and comparative biology has lagged behind. We hosted a symposium to bring together top researchers in the field of host associated microbes who also incorporate aspects of integrative and comparative biology. In this introduction, we highlight recent research demonstrating the profound roles that host-associated microbes play in many aspects of animal biology, such as immune function, endocrinology, and even behavior. It is our hope that integrative and comparative biologists will begin to include aspects of host-associated microbes into their research programs, enhancing both the fields of comparative biology and host-microbe interactions. PMID- 28992100 TI - Prenatal Exposure to LPS Alters The Intrarenal RAS in Offspring, Which Is Ameliorated by Adipose Tissue-Derived Mesenchymal Stem Cells. AB - BACKGROUND: Prenatal lipopolysaccharide (LPS) exposure causes hypertension in rat offspring through an unknown mechanism. Here, we investigated the role of the intrarenal renin-angiotensin system (RAS) in hypertension induced by prenatal LPS exposure and also explored whether adipose tissue-derived mesenchymal stem cells (ADSCs) can ameliorate the effects of prenatal LPS exposure in rat offspring. METHODS: Sixty-four pregnant rats were randomly divided into 4 groups (n = 16 in each), namely, a control group and an LPS group, which were intraperitoneally injected with vehicle and 0.79 mg/kg LPS, respectively, on the 8th, 10th, and 12th days of gestation; an ADSCs group, which was intravenously injected with 1.8 * 107 ADSCs on the 8th, 10th, and 12th days of gestation; and an LPS + ADSCs group, which received a combination of the treatments administered to the LPS and ADSCs groups. RESULTS: Prenatal LPS exposure increased blood pressure, Ang II expression, Ang II-positive, monocyte and lymphocyte, apoptotic cells in the kidney, and induced renal histological changes in offspring; however, the LPS and control groups did not differ significantly with respect to plasma renin activity levels, Ang II levels, or renal function. ADSCs treatment attenuated the blood pressure and also ameliorated the other effects of LPS-treated adult offspring. CONCLUSIONS: Prenatal exposure to LPS activates the intrarenal RAS but not the circulating RAS and thus induces increases in blood pressure in adult offspring; however, ADSCs treatment attenuates the blood pressure increases resulting from LPS exposure and also ameliorates the other phenotypic changes induced by LPS treatment by inhibiting intrarenal RAS activation. PMID- 28992101 TI - Low-Resolution Vision-at the Hub of Eye Evolution. AB - Simple roles for photoreception are likely to have preceded more demanding ones such as vision. The driving force behind this evolution is the improvement and elaboration of animal behaviors using photoreceptor input. Because the basic role for all senses aimed at the external world is to guide behavior, we argue here that understanding this "behavioral drive" is essential for unraveling the evolutionary past of the senses. Photoreception serves many different types of behavior, from simple shadow responses to visual communication. Based on minimum performance requirements for different types of tasks, photoreceptors have been argued to have evolved from non-directional receptors, via directional receptors, to low-resolution vision, and finally to high-resolution vision. Through this sequence, the performance requirements on the photoreceptors have gradually changed from broad to narrow angular sensitivity, from slow to fast response, and from low to high contrast sensitivity during the evolution from simple to more advanced and demanding behaviors. New behaviors would only evolve if their sensory performance requirements to some degree overlap with the requirements of already existing behaviors. This need for sensory "performance continuity" must have determined the order by which behaviors have evolved and thus been an important factor guiding animal evolution. Naturally, new behaviors are most likely to evolve from already existing behaviors with similar neural processing needs and similar motor responses, pointing to "neural continuity" as another guiding factor in sensory evolution. Here we use these principles to derive an evolutionary tree for behaviors driven by photoreceptor input. PMID- 28992099 TI - Co-adaption of tRNA gene copy number and amino acid usage influences translation rates in three life domains. AB - Although more and more entangled participants of translation process were realized, how they cooperate and co-determine the final translation efficiency still lacks details. Here, we reasoned that the basic translation components, tRNAs and amino acids should be consistent to maximize the efficiency and minimize the cost. We firstly revealed that 310 out of 410 investigated genomes of three domains had significant co-adaptions between the tRNA gene copy numbers and amino acid compositions, indicating that maximum efficiency constitutes ubiquitous selection pressure on protein translation. Furthermore, fast-growing and larger bacteria are found to have significantly better co-adaption and confirmed the effect of this pressure. Within organism, highly expressed proteins and those connected to acute responses have higher co-adaption intensity. Thus, the better co-adaption probably speeds up the growing of cells through accelerating the translation of special proteins. Experimentally, manipulating the tRNA gene copy number to optimize co-adaption between enhanced green fluorescent protein (EGFP) and tRNA gene set of Escherichia coli indeed lifted the translation rate (speed). Finally, as a newly confirmed translation rate regulating mechanism, the co-adaption reflecting translation rate not only deepens our understanding on translation process but also provides an easy and practicable method to improve protein translation rates and productivity. PMID- 28992102 TI - Invited Commentary: "Bedroom Light Exposure at Night and the Incidence of Depressive Symptoms: A Longitudinal Study of the HEIJO-KYO Cohort". AB - In modern society, we are increasingly disconnected from natural light/dark cycles and beset by round-the-clock exposure to artificial light. Light has powerful effects on physical and mental health, in part via the circadian system, and thus the timing of light exposure dictates whether it is helpful or harmful. In their compelling paper, Obayashi et al. (Am J Epidemiol. 2018;187(3):427-434.) offer evidence that light at night can prospectively predict an elevated incidence of depressive symptoms in older adults. Strengths of the study include the longitudinal design and direct, objective assessment of light levels, as well as accounting for multiple plausible confounders during analyses. Follow-up studies should address the study's limitations, including reliance on a global self-report of sleep quality and a 2-night assessment of light exposure that may not reliably represent typical light exposure. In addition, experimental studies including physiological circadian measures will be necessary to determine whether the light effects on depression are mediated through the circadian system or are so-called "direct" effects of light. In any case, these exciting findings could inform novel approaches to preventing depressive disorders in older adults. PMID- 28992103 TI - Maternal Programming of Body Weight in Syrian Hamsters. AB - Maternal programming of offspring energy balance has been viewed as an adaptation in which the gestational environment prepares the offspring to thrive and reproduce in that same postnatal environment. Programming might have the opposite effect, however, when gestational and postnatal environments are mismatched. Gestational programming would represent a trade-off if the mother can maximize fitness in one possible energetic future but cannot maximize fitness in another. The vast majority of research concerns rats, mice, or sheep, and dams are typically food restricted by 30-70% of ad libitum intake resulting in low birth weight and adult obesity in offspring. Few previous studies have used a lower level of food restriction, and no experiments, to the best of our knowledge, were designed to determine whether the effects of gestational restriction have postgestational effects independent of the effects that occurred during gestation. In the present experiment, Syrian hamsters were either restricted to 90% of their ad libitum food intake or fed ad libitum during pregnancy. All litters were cross-fostered at birth and all were fed ad libitum during lactation. Half of the litters from ad libitum-fed pregnant dams were fostered to dams that had been food restricted during pregnancy and half of the litters from food-restricted pregnant dams were fostered to ad libitum-fed dams. The latter group allowed us to test the hypothesis that the effects of having a gestationally food-restricted mother affects offspring characteristics independent of the prenatal programming. First, we found significant increases in the postnatal body weight of the offspring of ad libitum-fed mothers fostered to food-restricted dams, supporting the hypothesis that the effects of gestational restriction carry over to postnatal maternal ability (e.g., milk yield, milk content, or parental behavior). Second, the carry-over effects of gestational food restriction on offspring postnatal body weight were significant in male but not female offspring. This occurred even though this group had significantly lower food intake than offspring of ad libitum-fed mothers with ad libitum-fed foster mothers. In addition, and contrary to expectation, gestational food restriction had no significant effect on adult baseline food hoarding or food hoarding in response to food restriction. These results suggest that even mild energetic challenges during gestation can have postgestational effects on maternal ability, and the effects on offspring are sex-specific. PMID- 28992104 TI - A simplified and sensitive method to identify Alzheimer's disease biomarker candidates using patient-derived induced pluripotent stem cells (iPSCs). AB - We developed a simplified and sensitive method to identify Alzheimer's disease (AD) biomarker candidates by a quantitative and targeted proteomic analysis (combination of liquid chromatography tandem mass spectrometry and multiplexed multiple reaction monitoring/selected reaction monitoring analysis) of culture media from neurons differentiated from induced pluripotent stem cells (iPSCs) established from AD patients. We found that alpha-1-acid glycoprotein (ORM1) was decreased in the culture media of AD-iPSC-derived neurons, consistent with previous observations for AD patient cerebrospinal fluid, thus validating our new strategy. Moreover, our method is applicable for identifying biomarker candidates for other neurodegenerative disorders using patient-derived iPSCs. PMID- 28992105 TI - The Effects of Food Availability on the Sexual Behavior of Meadow Voles. AB - Two competing hypotheses have been used to explain species and sex differences in the effects of food availability on the sexual behavior of mammals. One hypothesis, the metabolic fuels hypothesis, posits that individuals, primarily females, forgo reproduction when faced with food deprivation and invest their limited resources in behaviors not associated with reproduction. The other hypothesis, the reproduction at all costs hypothesis, states that individuals, males and females, continue to reproduce or increase their reproductive behavior when faced with food deprivation. Results show female voles followed the predictions of the metabolic fuels hypothesis. That is, food-deprived female meadow voles were less attractive, proceptive, and receptive toward males than were female voles that had continuous access to food. Dams that were food deprived late in lactation failed to enter postpartum estrus, a period of heightened sexual receptivity that occurs immediately after parturition. Females that were food deprived during the first or second week of lactation spent less time involved in maternal care compared to dams that were not food deprived. In contrast, male voles mainly followed the reproduction at all costs hypothesis. Food-deprived male voles were as attractive, as proceptive, and as sexually receptive toward females as were males that had continuous access to food. PMID- 28992106 TI - A simple method for environmental cell depressurization for use with an electron microscope. AB - With the aid of the environmental cell (EC) in electron microscopy, hydrated specimens have been observed at high resolutions that optical microscopy cannot attain. Due to the ultra-high vacuum conditions of the inner column of the electron microscope, the EC requires sealing films that are sufficiently thin to allow electron transmission and that are sufficiently tough to withstand the pressure difference between the inside and outside of the EC. However, most hydrated specimens can be observed at low vacuum because the saturated vapor pressure of water is known to be 0.02 atm at room temperature. These concepts have been used in the differential pumping system, but it is complicated and relatively expensive. In this work, we propose a simple method for depressurization of the EC using a 'balloon structure' and demonstrate the theoretical benefits and practical improvement for specimen observations in low vacuum conditions. PMID- 28992107 TI - Flow in the anterior chamber of the eye with an implanted iris-fixated artificial lens. AB - Flow in the aqueous humour that fills the anterior chamber of the eye occurs in response to the production and drainage of the aqueous humour, and also due to buoyancy effects produced by thermal gradients. Phakic intraocular lenses are manufactured lenses that are surgically inserted in the eyes of patients to correct refractive errors. Their presence has a dramatic effect on the circulation of the aqueous humour, resulting a very different flow in the anterior chamber, the effects of which have not been extensively investigated. In this article we use a simplified mathematical model to analyse the flow, in order to assess the effect of the implanted lens on the pressure drop required to drive the flow and also on the wall shear stress experienced by the corneal endothelial cells and the cells of the iris. A high pressure drop could result in an increased risk of glaucoma, whilst raised shear stress on the cornea could result in a reduction in the density of endothelial cells there, and on the iris it could result in the detachment of pigment cells, which block the outflow of the eye, also leading to glaucoma. Our results confirm those of previous fully numerical studies, and show that, although the presence of the lens causes significant differences in the flow topology and direction, the typical magnitudes of the shear stress are not significantly changed from the natural case. Our semi-analytical solution allows us to perform a thorough study of the dependence of the results on the controlling parameters and also to understand the basic physical mechanisms underlying flow characteristics. PMID- 28992108 TI - Defining the Role of the MADS-Box Gene, Zea Agamous-like1, a Target of Selection During Maize Domestication. AB - Genomic scans for genes that show the signature of past selection have been widely applied to a number of species and have identified a large number of selection candidate genes. In cultivated maize (Zea mays ssp. mays) selection scans have identified several hundred candidate domestication genes by comparing nucleotide diversity and differentiation between maize and its progenitor, teosinte (Z. mays ssp. parviglumis). One of these is a gene called zea agamous like1 (zagl1), a MADS-box transcription factor, that is known for its function in the control of flowering time. To determine the trait(s) controlled by zagl1 that was (were) the target(s) of selection during maize domestication, we created a set of recombinant chromosome isogenic lines that differ for the maize versus teosinte alleles of zagl1 and which carry cross-overs between zagl1 and its neighbor genes. These lines were grown in a randomized trial and scored for flowering time and domestication related traits. The results indicated that the maize versus teosinte alleles of zagl1 affect flowering time as expected, as well as multiple traits related to ear size with the maize allele conferring larger ears with more kernels. Our results suggest that zagl1 may have been under selection during domestication to increase the size of the maize ear. PMID- 28992109 TI - Integrin beta1 is bound to galectin-1 in human trophoblast. AB - Interaction of sugar binding proteins-galectins, with glycoconjugates is considered relevant for various reproductive processes. Galectin-1 (gal-1) is a molecule involved in trophoblast cell invasion, which is accomplished through interaction with cell surface and/or extracellular matrix glycoproteins. A possibility of interaction of endogenous gal-1 and trophoblast beta1 integrins, both previously shown relevant for trophoblast invasion, was investigated. Confocal microscopy showed overlap in gal-1 and beta1 integrin localization at the plasma membrane of isolated cytotrophoblast, HTR-8/SVneo extravillous trophoblast cell line and JAr choriocarcinoma cells. Immunoprecipitation confirmed an interaction of gal-1 with integrin beta1, but not with alpha1 or alpha5 integrin subunits. Nondenaturing electrophoresis and subcellular fractionation suggested association of gal-1 with beta1 integrin in intracellular and plasma membrane compartments of HTR-8/SVneo cells. Gal-1/beta1 integrin complex was sensitive to chemical and enzyme treatments, indicating carbohydrate dependent interaction. Down-regulation of gal-1 by siRNA, however, had no effect on level or distribution of beta1 integrin, as determined by qPCR and flow cytometry. These results suggest complex lectin type interaction of gal-1 with beta1 integrin at the trophoblast cell membrane, which could influence trophoblast cell adhesion, migration and invasion. PMID- 28992111 TI - Refractory Pseudomonas Bacteremia in a 2-Year-Old Sterilized by Bacteriophage Therapy. AB - Here, we report a complex case that involved a pediatric patient who experienced recalcitrant multidrug-resistant Pseudomonas aeruginosa infection complicated by bacteremia/sepsis; our antibacterial options were limited because of resistance, allergies, and suboptimal source control. A cocktail of 2 bacteriophages targeting the infectious organism introduced on 2 separate occasions sterilized the bacteremia. PMID- 28992110 TI - NFAT3/c4-mediated excitotoxicity in hippocampal apoptosis during radiation induced brain injury. AB - Whole brain irradiation (WBI) has become an indispensible tool in the treatment of head and neck cancer, and it has greatly improved patient survival rate and total survival time. In addition, prophylactic cranial irradiation (PCI) has dramatically decreased the incidence of brain metastatic carcinoma. However, WBI may induce temporary functional deficits or even progressive, irreversible cognitive dysfunction that compromises the quality of life for survivors. Unfortunately, the exact molecular mechanisms for cognitive damage remain elusive, and no treatment or preventative measures are available for use in the clinic. In the present study, the nuclear factor of activated T cells isoform 4 (NFAT3/c4) was found to play a vital role in excitotoxic hippocampus cell apoptosis induced by radiation. Sprague-Dawley (SD) rats received 20 Gy WBI, after which we detected NFAT3/c4-mediated excitotoxicity. We found that radiation caused hippocampus excitotoxicity, resulting from overactivation of the N-methyl D-aspartate receptor (NMDAR) and always accompanied by subsequent elevation of the intracellular calcium level and activation of calcineurin (CaN). P-NFAT3/c4 was the principal downstream target of CaN, including regulation of its nuclear translocation as well as transcriptional activities. Radiation recruited NMDAR/NFAT3/c4 activation and subsequent Bax induction in hippocampus cells. Once treated with the NFAT3/c4 inhibitor 11R-VIVIT peptide pre-irradiation, hippocampal proliferation and neuron survival (dentate gyrus cells in particular) were protected from radiation-induced injury, resulting in inhibition of the apoptosis marker Bax. Our principal aim was to illuminate the role of NFAT3/c4 mediated excitotoxicity in hippocampal apoptosis during radiation-induced brain injury. This study is the first time that radiation-induced activation of NFAT3/c4 has been recorded, and our results suggest that NFAT3/c4 may be a novel target for prevention and treatment of radiation-induced brain injury. PMID- 28992112 TI - Comparison of Optimal Diagnostic Thresholds of Hypertension With Home Blood Pressure Monitoring and 24-Hour Ambulatory Blood Pressure Monitoring. AB - BACKGROUND: Differences between the recently suggested outcome-driven diagnostic threshold of home blood pressure (HBP) measurements and the currently recommended diagnostic threshold of HBP measurements may cause a disagreement between 24-hour ambulatory blood pressure (ABP) and HBP measurements in the diagnosis of hypertension. We evaluated the agreement of various HBP diagnostic thresholds (135/85, 130/85, and 130/80 mm Hg) to ABP measurements, as a reference method. METHODS: Patients who were confirmed to have high BP (>=140/90 mm Hg) at the outpatient clinic were referred. HBP measurement was performed for 7 days in triplicates every morning and evening. The 24-hour ABP measurement was performed on the 8th day. Using 24-hour ABP measurement as a reference method, we analyzed HBP diagnostic thresholds at 135/85, 130/85, and 130/80 mm Hg. RESULTS: Among 319 patients, 256 patients (mean age, 51.8 +/- 9.7 years; 119 men) with valid HBP measurements and 24-hour ABP measurements were enrolled. The threshold of 130/80 mm Hg showed the highest diagnostic sensitivity (P = 0.001) with diagnostic agreement by Kappa statistics. Using 130/80 mm Hg as a diagnostic threshold of hypertension, the prevalence of masked hypertension was significantly lower than 130/85 and 135/85 mm Hg (7.8, 15.2, and 18.4%, respectively, P = 0.002). CONCLUSIONS: The present study suggests that lowering the diagnostic thresholds of HBP measurement from 135/85 mm Hg to 130/80 mm Hg may improve diagnostic accuracy for hypertension. PMID- 28992113 TI - Two transcriptional activators of N-acetylserotonin O-methyltransferase 2 and melatonin biosynthesis in cassava. AB - Similar to the situation in animals, melatonin biosynthesis is regulated by four sequential enzymatic steps in plants. Although the melatonin synthesis genes have been identified in various plants, the upstream transcription factors of them remain unknown. In this study on cassava (Manihot esculenta), we found that MeWRKY79 and heat-shock transcription factor 20 (MeHsf20) targeted the W-box and the heat-stress elements (HSEs) in the promoter of N-acetylserotonin O methyltransferase 2 (MeASMT2), respectively. The interaction between MeWRKY79, MeHsf20, and the MeASMT2 promoter was evidenced by the activation of promoter activity and chromatin immunoprecipitation (ChIP) in cassava protoplasts, and by an in vitro electrophoretic mobility shift assay (EMSA). The transcripts of MeWRKY79, MeHsf20, and MeASMT2 were all regulated by a 22-amino acid flagellin peptide (flg22) and by Xanthomonas axonopodis pv manihotis (Xam). In common with the phenotype of MeASMT2, transient expression of MeWRKY79 and MeHsf20 in Nicotiana benthamiana leaves conferred improved disease resistance. Through virus induced gene silencing (VIGS) in cassava, we found that MeWRKY79- and MeHsf20 silenced plants showed lower transcripts of MeASMT2 and less accumulation of melatonin, which resulted in disease sensitivity that could be reversed by exogenous melatonin. Taken together, these results indicate that MeASMT2 is a target of MeWRKY79 and MeHsf20 in plant disease resistance. This study identifies novel upstream transcription factors of melatonin synthesis genes in cassava, thus extending our knowledge of the complex modulation of melatonin synthesis in plant defense. PMID- 28992114 TI - Feasibility of Using the Helping Alliance Questionnaire II as a Self-Report Measure for Individuals with a Psychiatric Disorder Receiving Music Therapy. AB - Background: No specific instrument has been developed for measuring alliance during music therapy. Objective: To evaluate the feasibility of using the Helping Alliance Questionnaire II (HAq-II) as a self-report measure for individuals receiving treatment for a psychiatric disorder. Specifically, we examined the percent of patients who filled out the questionnaire, and when completed, whether there were any missing items. We also examined internal consistency and associations between patient variables and HAq-II scores. Methods: Between October 2013 and April 2014, we invited 45 individuals with a psychiatric disorder, who were also receiving music therapy, to fill out the HAq-II. We also collected clinical data from each person's record. Results: Thirty-one (69%) of the 45 invited patients filled out the HAq-II, and of those completed, only three had missing items. Of the 45 invited patients, thirty (67%) had a diagnosis of schizophrenia or other psychotic disorders, and 11 (24%) were diagnosed with other psychiatric disorders. In terms of diagnosis and other clinical variables, no statistically significant differences were found between the 31 patients who filled out the HAq-II and the 14 patients who did not return the questionnaire. The median HAq-II score was 5.11 (range 3.74-6.00), indicating a relatively high alliance. We did not find any statistically significant associations between the HAq-II scores and potential predictors of interest. The Cronbach's alpha was 0.85. Conclusions: Completion of the HAq-II was fairly high in this group of individuals with psychiatric diagnoses who were receiving music therapy. Internal consistency of the HAq-II was acceptable. Relatively high HAq-II scores suggest a high degree of therapeutic alliance, but the external validity of the HAq-II and the relationship between scores and therapy needs further evaluation. PMID- 28992115 TI - How Song Experience Affects Female Mate-Choice, Male Song, and Monoaminergic Activity in the Auditory Telencephalon in Lincoln's Sparrows. AB - A sexual signal can indicate not only the signaler's attractiveness as a potential mate but also the signaler's competitiveness relative to rivals. As the attractiveness or competitiveness of the prevailing signaling environment increases, individuals prospecting for mates should change their choice threshold, whereas competing individuals should shift resources toward elevating their own competitiveness. Previous studies show that experimental elevations of song competition increase male competitive behavior in Lincoln's sparrows (Melospiza lincolnii) and European starlings (Sturnus vulgaris). Through a series of experimental manipulations using laboratory-housed Lincoln's sparrows, we have also discovered that females change the strength of their song preferences depending on the attractiveness of the song environment to which they have recently been exposed; compared to a less-attractive environment, a highly attractive environment elevates the threshold for releasing phonotaxis behavior toward male song. These behavioral adjustments are associated with changes in forebrain monoaminergic activity that are triggered by experimental manipulations of the quality of the song environment. Findings from these studies suggest possible neural mechanisms for the regulation of adaptive behavioral plasticity associated with dynamic sexual signaling environments. PMID- 28992116 TI - In vitro activity of echinocandins against 562 clinical yeast isolates from a Romanian multicentre study. AB - The study presents the echinocandin susceptibility profile of a multi-centre collection of pathogenic yeast isolates from Romanian tertiary hospitals. The 562 isolates were identified using ID32C strips, MALDI-TOF MS and DNA sequencing. Minimal inhibitory concentrations (MICs) of caspofungin (CAS), micafungin (MCA), and anidulafungin (ANI) were assessed and interpreted according to EUCAST guidelines. Minimal fungicidal concentrations (MFC) were determined by plating content from the clear MIC wells. The activity was considered fungicidal at MFC/MIC <= 4. The three echinocandins had strongly correlated MICs and high percentages of MIC essential agreement. Most often, MCA had the lowest MICs, followed by CAS and ANI. Against C. parapsilosis and C. kefyr, CAS had the lowest MIC values. The MIC50 values were between 0.03 and 0.25 mg/l, except C. parapsilosis. The MIC90 values were usually one dilution higher. MFCs and MICs were weakly correlated. ANI and MCA had the lowest MFC values. The MFC50 values were between 0.06 and 0.5 mg/l, except C. parapsilosis, C. guilliermondii, and C. dubliniensis. The MFC90 values were usually two dilutions higher. Based on EUCAST breakpoints, 47 isolates (8.4%) were resistant to at least one echinocandin, most often ANI. Most resistant isolates were of C. albicans, C. glabrata, and C. krusei. There were 17 isolates (3%) resistant to echinocandins and fluconazole and most belonged to the same three species. MCA and ANI had the highest rates of fungicidal activity. The high rates of echinocandin resistance and significant multidrug resistance make prophylaxis and empiric therapy difficult. PMID- 28992118 TI - Integration of multiple signaling pathways shapes the auxin response. AB - The phytohormone auxin is a pivotal signaling molecule that functions throughout the plant lifecycle. Proper regulation of the auxin response is critical for optimizing plant growth under ever-changing environmental conditions. Recent studies have demonstrated that the signaling components that modulate auxin sensitivity and responses are functionally and mechanically diverse. In addition to auxin itself, various environmental and hormonal signals are integrated to modulate the auxin response through directly controlling auxin signaling components. This review explores the non-canonical mechanisms that modulate auxin signaling components, including transcriptional, translational, and post translational regulation. All of these contribute to the wide range in sensitivity and complexity in auxin responses to various signaling cues. PMID- 28992117 TI - Diversity of cis-regulatory elements associated with auxin response in Arabidopsis thaliana. AB - The phytohormone auxin regulates virtually every developmental process in land plants. This regulation is mediated via de-repression of DNA-binding auxin response factors (ARFs). ARFs bind TGTC-containing auxin response cis-elements (AuxREs), but there is growing evidence that additional cis-elements occur in auxin-responsive regulatory regions. The repertoire of auxin-related cis-elements and their involvement in different modes of auxin response are not yet known. Here we analyze the enrichment of nucleotide hexamers in upstream regions of auxin-responsive genes associated with auxin up- or down-regulation, with early or late response, ARF-binding domains, and with different chromatin states. Intriguingly, hexamers potentially bound by basic helix-loop-helix (bHLH) and basic leucine zipper (bZIP) factors as well as a family of A/T-rich hexamers are more highly enriched in auxin-responsive regions than canonical TGTC-containing AuxREs. We classify and annotate the whole spectrum of enriched hexamers and discuss their patterns of enrichment related to different modes of auxin response. PMID- 28992119 TI - A reproducible and scalable procedure for preparing bacterial extracts for cell free protein synthesis. AB - Cell-free protein synthesis is a useful method for preparing proteins for functional or structural analyses. However, batch-to-batch variability with regard to protein synthesis activity remains a problem for large-scale production of cell extract in the laboratory. To address this issue, we have developed a novel procedure for large-scale preparation of bacterial cell extract with high protein synthesis activity. The developed procedure comprises cell cultivation using a fermentor, harvesting and washing of cells by tangential flow filtration, cell disruption with high-pressure homogenizer and continuous diafiltration. By optimizing and combining these methods, ~100 ml of the cell extract was prepared from 150 g of Escherichia coli cells. The protein synthesis activities, defined as the yield of protein per unit of absorbance at 260 nm of the cell extract, were shown to be reproducible, and the average activity of several batches was twice that obtained using a previously reported method. In addition, combinatorial use of the high-pressure homogenizer and diafiltration increased the scalability, indicating that the cell concentration at disruption varies from 0.04 to 1 g/ml. Furthermore, addition of Gam protein and examinations of the N terminal sequence rendered the extract prepared here useful for rapid screening with linear DNA templates. PMID- 28992121 TI - Auxin and above-ground meristems. AB - In contrast to animals, plants maintain life-long post-embryonic organogenesis from specialized tissues termed meristems. Shoot meristems give rise to all aerial tissues and are precisely regulated to balance stem cell renewal and differentiation. The phytohormone auxin has a dynamic and differential distribution within shoot meristems and during shoot meristem formation. Polar auxin transport and local auxin biosynthesis lead to auxin maxima and minima to direct cell fate specification, which are critical for meristem formation, lateral organ formation, and lateral organ patterning. In recent years, feedback regulatory loops of auxin transport and signaling have emerged as major determinants of the self-organizing properties of shoot meristems. Systems biology approaches, which involve molecular genetics, live imaging, and computational modeling, have become increasingly important to unravel the function of auxin signaling in shoot meristems. PMID- 28992120 TI - Relationships between iron dose, hospitalizations and mortality in incident haemodialysis patients: a propensity-score matched approach. AB - Background: Intravenous iron management is common in the haemodialysis population. However, the safest dosing strategy remains uncertain, in terms of the risk of hospitalization and mortality. We aimed to determine the effects of cumulative monthly iron doses on mortality and hospitalization. Methods: This multicentre observational retrospective propensity-matched score study included 1679 incident haemodialysis patients. We measured baseline demographic variables, haemodialysis clinical parameters and laboratory analytical values. We compared outcomes among quartiles of cumulative iron dose (mg/kg/month). We implemented propensity-score matching (PSM) to reduce confounding due to indication. In the PSM cohort (330 patients), we compared outcomes between groups that received cumulative iron doses above and below 5.66 mg/kg/month. Results: Kaplan-Meier analyses showed that the high iron dose group had significantly worse survival than the low iron dose group. A univariate analysis indicated that the monthly iron dose could significantly predict mortality. However, a multivariate regression did not confirm that finding. The multivariate regression analysis revealed that iron doses >5.58 mg/kg/month were not associated with elevated mortality risk, but they were associated with elevated risks of all-cause and cardiovascular-related hospitalizations. These results were ratified in the PSM population. Conclusions: Intravenous iron administration is advisable for maintaining haemoglobin levels in patients that receive haemodialysis. Our data suggested that large monthly iron doses, adjusted for body weight, were associated with more hospitalizations, but not with mortality or infection related hospitalizations. PMID- 28992122 TI - A cheminformatics review of auxins as herbicides. AB - Herbicides are an important asset in ensuring food security, especially when faced with an ever-increasing demand on food production to feed the global population. The current selection of herbicides is increasingly encountering resistance in agricultural weeds they once targeted effectively. It is imperative that new compounds or more effective modes of action are discovered in order to overcome this resistance. This cheminformatics review looks at current herbicides and evaluates their physiochemical properties on a class-by-class basis. We focus in particular on the synthetic auxin herbicides, Herbicide Resistance Action Committee class O, analyzing these against herbicides more generally and for class-specific features such as mobility in plant vasculature. We summarise the physiochemical properties of all 24 compounds used commercially as auxins and relate these results to ongoing approaches to novel auxin discovery. We introduce an interactive, open source cheminformatics tool known as DataWarrior for herbicide discovery, complete with records for over 300 herbicidal compounds. We hope this tool helps researchers as part of a rational approach to not only auxin discovery but agrochemical discovery in general. PMID- 28992123 TI - Whole-exome sequencing identifies a novel INS mutation causative of maturity onset diabetes of the young 10. AB - Monogenic diabetes is often misdiagnosed with type 2 diabetes due to overlapping characteristics. This study aimed to discover novel causative mutations of monogenic diabetes in patients with clinically diagnosed type 2 diabetes and to explore potential molecular mechanisms. Whole-exome sequencing was performed on 31 individuals clinically diagnosed with type 2 diabetes. One novel heterozygous mutation (p.Ala2Thr) in INS was identified. It was further genotyped in an additional case-control population (6523 cases and 4635 controls), and this variant was observed in 0.09% of cases. Intracellular trafficking of insulin proteins was assessed in INS1-E and HEK293T cells. p.Ala2Thr preproinsulin-GFP was markedly retained in the endoplasmic reticulum (ER) in INS1-E cells. Activation of the PERK-eIF2alpha-ATF4, IRE1alpha-XBP1, and ATF6 pathways as well as upregulated ER chaperones were detected in INS1-E cells transfected with the p.Ala2Thr mutant. In conclusion, we identified a causative mutation in INS responsible for maturity-onset diabetes of the young 10 (MODY10) in a Chinese population and demonstrated that this mutation affected beta cell function by inducing ER stress. PMID- 28992124 TI - Impact of trajectories of abdominal aortic calcification over 2 years on subsequent mortality: a 10-year longitudinal study. AB - Background: Although both the presence and progression over time of vascular calcification have been shown to independently predict cardiovascular disease and mortality in chronic dialysis patients, the impact of the pattern of accumulation of abdominal aortic calcification on mortality has not yet been investigated. Methods: We conducted a longitudinal study at a dialysis hospital in Hokkaido, Japan from 2005 to 2014. An abdominal calcification index (ACI) was generated for 396 patients from their annual abdominal computed tomography (CT) scans. The trajectories of ACIs during the first 2 years were classified using group-based trajectory modeling into four groups; stable (29.0%), slow increase (29.2%), rapid nonlinear increase (24.4%) and advanced with slow increase (17.4%). Incidence rates by group of all-cause mortality during the follow-up period (mean of 4.5 years) were investigated using the Cox proportional hazard model. Results: Compared with the stable trajectory, both the rapid nonlinear increase and the advanced with slow increase trajectories were associated with an increased risk of death [adjusted hazard ratios (HR) 1.91; 95% confidence interval (CI) 1.02 3.58 and adjusted HR 2.79; 95% CI: 1.44-5.11, respectively]. Sensitivity analyses indicated that ACI trajectories were associated with subsequent mortality, while ACI at individual time points was not. Conclusions: Chronic hemodialysis patients with a trajectory of longitudinal high or rapid accumulation of vascular calcification over time were at a higher risk of death. Individual trajectories of vascular calcification may be suggested to allow for more accurate mortality risk calculations than one-time assessment. PMID- 28992125 TI - A new method for studying cryptococcosis in a murine model using 99mTc Cryptococcus gattii. AB - Cryptococcus gattii is one of the etiologic agents of cryptococcosis, a systemic mycosis that occurs in healthy and immunosuppressed humans and animals worldwide. Primary pulmonary infection caused by C. gattii is usually followed by fungal dissemination to the central nervous system, resulting in high mortality rates. In this context, animal models of cryptococcosis are useful in the study of fungal pathogenesis and host response against the pathogen, and for testing novel therapeutic options. The most frequently applied method to study fungal dissemination from the lungs to other organs is by culturing tissues, which is not accurate for the detection and quantification of fungal load at early stages of the infection. To overcome this problem, the purpose of this study was to develop a new method for the quantification of Cryptococcus dissemination. One C. gattii strain was efficiently radiolabeled with technetium-99m (99mTc), without affecting viability of the cells. Further, the 99mTc-C. gattii (111 MBq) strain was used to infect mice by intratracheal and intravenous route for biodistribution studies. 99mTc-C. gattii was successfully used in detection of the yeast in the brain of mice 6 hours postinoculation, while the detection using colony forming units was possible only 24 hours postinfection. Our results provided an alternative method that could be applied in further investigations regarding the efficacy of antifungals, fungal virulence, and host-pathogen interactions. PMID- 28992126 TI - Association Between Vancomycin Trough Concentrations and Duration of Methicillin Resistant Staphylococcus aureus Bacteremia in Children. AB - In a multicenter retrospective study, we sought to determine the optimal vancomycin trough concentration that would impact the duration of methicillin resistant Staphylococcus aureus bacteremia in children. We found that a median vancomycin trough concentration of <10 ug/mL within the first 72 hours may be associated with a longer duration of bacteremia compared to a median trough concentration of >=10 ug/mL. PMID- 28992127 TI - Can we further enrich autosomal dominant polycystic kidney disease clinical trials for rapidly progressive patients? Application of the PROPKD score in the TEMPO trial. AB - Background: The PROPKD score has been proposed to stratify the risk of progression to end-stage renal disease in autosomal dominant polycystic kidney disease (ADPKD) subjects. We aimed to assess its prognostic value in a genotyped subgroup of subjects from the Tolvaptan Phase 3 Efficacy and Safety Study in Autosomal Dominant Polycystic Kidney Disease (TEMPO3/4) trial. Methods: In the post hoc analysis, PKD1 and PKD2 were screened in 770 subjects and the PROPKD score was calculated in mutation-positive subjects (male: 1 point; hypertension <35 years: 2 points; first urologic event <35 years: 2 points; nontruncating PKD1 mutation: 2 points; truncating PKD1 mutation: 4 points). Subjects were classified into low-risk (LR; 0-3 points), intermediate-risk (IR; 4-6 points) and high-risk (HR; 7-9 points) groups. Results: The PROPKD score was calculated in 749 subjects (LR = 132, IR = 344 and HR = 273); age was inversely related to risk (LR = 43.6 years, IR = 39.5 years, HR = 36.2 years; P < 0.001). Subjects from the HR group had significantly higher height-adjusted total kidney volume (TKV) and rates of TKV growth. While baseline renal function was similar across all risk groups, the rate of estimated glomerular filtration rate (eGFR) decline significantly increased from LR to HR in the placebo group. Tolvaptan treatment effectiveness to reduce TKV growth was similar in all three risk categories. While tolvaptan significantly slowed eGFR decline in the IR (tolvaptan = -2.34 versus placebo = 3.33 mL/min/1.73 m 2 /year; P = 0.008) and HR groups (tolvaptan = -2.74 versus placebo = -3.94 mL/min/1.73 m 2 /year; P = 0.002), there was no difference in the LR group (tolvaptan = -2.35 versus placebo = -2.50 mL/min/1.73 m 2 /year; P = 0.72). Excluding the LR subjects from the analysis improved the apparent treatment effect of tolvaptan on eGFR decline. Conclusion: This study confirms the prognostic value of the PROPKD score and suggests that it could reduce costs and enhance endpoint sensitivity by enriching future study populations for rapidly progressing ADPKD subjects. PMID- 28992128 TI - Peroxisomal CuAOzeta and its product H2O2 regulate the distribution of auxin and IBA-dependent lateral root development in Arabidopsis. AB - Root system architecture depends on endogenous and environmental signals, including polar transport of the phytohormone auxin, reactive oxygen species (ROS), nutrient availability, and stresses. In our study, we describe a novel Arabidopsis thaliana peroxisome-localized copper amine oxidase zeta (CuAOzeta), which is highly expressed in cortical cells, and the ROS derived from CuAOzeta are essential for lateral root (LR) development. Loss of CuAOzeta results in retarded auxin-induced ROS generation, PINFORMED2 (PIN2)-mediated auxin transport, and LR development in response to added indole-3-butyric acid. Auxins enhance CuAOzeta protein levels and their cellular translocation toward the plasma membrane in the cortex. CuAOzeta interacts physically with PEROXINS5 via an N-terminal signal tag, Ser-Lys-Leu, and is transported into the peroxisome upon this interaction, which is required for the functions of CuAOzeta in the auxin response. Together, our results suggest a peroxisomal ROS-based auxin signaling pathway involving spatiotemporal-dependent CuAOzeta functional regulation of PIN2 homeostasis, auxin distribution, and LR development. PMID- 28992129 TI - Development and validation of a prediction model for loss of physical function in elderly hemodialysis patients. AB - Background: Among aging hemodialysis patients, loss of physical function has become a major issue. We developed and validated a model of predicting loss of physical function among elderly hemodialysis patients. Methods: We conducted a cohort study involving maintenance hemodialysis patients >=65 years of age from the Dialysis Outcomes and Practice Pattern Study in Japan. The derivation cohort included 593 early phase (1996-2004) patients and the temporal validation cohort included 447 late-phase (2005-12) patients. The main outcome was the incidence of loss of physical function, defined as the 12-item Short Form Health Survey physical function score decreasing to 0 within a year. Using backward stepwise logistic regression by Akaike's Information Criteria, six predictors (age, gender, dementia, mental health, moderate activity and ascending stairs) were selected for the final model. Points were assigned based on the regression coefficients and the total score was calculated by summing the points for each predictor. Results: In total, 65 (11.0%) and 53 (11.9%) hemodialysis patients lost their physical function within 1 year in the derivation and validation cohorts, respectively. This model has good predictive performance quantified by both discrimination and calibration. The proportion of the loss of physical function increased sequentially through low-, middle-, and high-score categories based on the model (2.5%, 11.7% and 22.3% in the validation cohort, respectively). The loss of physical function was strongly associated with 1-year mortality [adjusted odds ratio 2.48 (95% confidence interval 1.26-4.91)]. Conclusions: We developed and validated a risk prediction model with good predictive performance for loss of physical function in elderly hemodialysis patients. Our simple prediction model may help physicians and patients make more informed decisions for healthy longevity. PMID- 28992130 TI - Stomatal conductance, mesophyll conductance, and transpiration efficiency in relation to leaf anatomy in rice and wheat genotypes under drought. AB - Increasing leaf transpiration efficiency (TE) may provide leads for growing rice like dryland cereals such as wheat (Triticum aestivum). To explore avenues for improving TE in rice, variations in stomatal conductance (gs) and mesophyll conductance (gm) and their anatomical determinants were evaluated in two cultivars from each of lowland, aerobic, and upland groups of Oryza sativa, one cultivar of O. glaberrima, and two cultivars of T. aestivum, under three water regimes. The TE of upland rice, O. glaberrima, and wheat was more responsive to the gm/gs ratio than that of lowland and aerobic rice. Overall, the explanatory power of the particular anatomical trait varied among species. Low stomatal density mostly explained the low gs in drought-tolerant rice, whereas rice genotypes with smaller stomata generally responded more strongly to drought. Compared with rice, wheat had a higher gm, which was associated with thicker mesophyll tissue, mesophyll and chloroplasts more exposed to intercellular spaces, and thinner cell walls. Upland rice, O. glaberrima, and wheat cultivars minimized the decrease in gm under drought by maintaining high ratios of chloroplasts to exposed mesophyll cell walls. Rice TE could be improved by increasing the gm/gs ratio via modifying anatomical traits. PMID- 28992131 TI - Continent-Wide Climatic Variation Drives Local Adaptation in North American White Clover. AB - Climate-associated clines in adaptive polymorphisms are commonly cited as evidence of local adaptation within species. However, the contribution of the clinally varying trait to overall fitness is often unknown. To address this question, we examined survival, vegetative growth, and reproductive output in a central US common garden experiment using 161 genotypes of white clover (Trifolium repens L.) originating from 15 locations across North America. White clover is polymorphic for cyanogenesis (hydrogen cyanide release upon tissue damage), a chemical defense against generalist herbivores, and climate-associated cyanogenesis clines have repeatedly evolved across the species range. Over a 12 month experiment, we observed striking correlations between the population of origin and plant performance in the common garden, with climatic distance from the common garden site predicting fitness more accurately than geographic distance. Assessments of herbivore leaf damage over the 2015 growing season indicated marginally lower herbivory on cyanogenic plants; however, this effect did not result in increased fitness in the common garden location. Linear mixed modeling suggested that while cyanogenesis variation had little predictive value for vegetative growth, it is as important as climatic variation for predicting reproductive output in the central United States. Together, our findings suggest that knowledge of climate similarity, as well as knowledge of locally favored adaptive traits, will help to inform transplantation strategies for restoration ecology and other conservation efforts in the face of climate change. PMID- 28992132 TI - DNA strand breaks in peripheral blood leucocytes of Polish blood donors. AB - Knowledge about the basal level of DNA damage in leucocytes of healthy control populations is essential before estimation of the effects of exposure to external agents in biomonitoring studies. The aim of this study was to analyse the effects of some lifestyle factors on baseline DNA damage in leucocytes of humans. The material consisted of the peripheral blood from 276 healthy volunteer blood donors. In addition to the standard blood donation questionnaire, they were asked about age, gender, occupation, radiological history, smoking habit, alcohol consumption, medicine use and pet ownership. The results showed marked intra individual variability. Significant differences in DNA damage levels were observed between individuals in different age and sex groups, between smokers and non-smokers and between samples taken in different seasons of the year, with the highest DNA damage in those obtained in the summer. Significantly higher levels of DNA damage were noted in leucocytes of donors older than 29 years, in men compared with women and in male smokers. Significantly higher DNA strand breaks were observed in heavy smokers. A non-significantly higher level of DNA damage was observed in individuals subjected to radiological investigation and in those drinking alcohol, whereas lower levels were observed in leucocytes of pet owners and in donors taking medicines. Pet ownership influences the level of DNA damage and there is an interaction between this effect and that of smoking. The smoker/pet owners showed almost half the level of DNA damage of smokers without pets. The current results confirmed high intra-individual variability between the levels of DNA damage of individuals. The significant factors that influence the DNA damage in leucocytes are age, sex and smoking habit, especially in men and in heavy smokers. The finding of reduced DNA damage in the leucocytes of pet owners suggests the tendency towards a beneficial effect of such company. PMID- 28992134 TI - Risk of new-onset diabetes in end-stage renal disease patients undergoing dialysis: analysis from registry data of Taiwan. AB - Background: This study compared the risk of developing new-onset diabetes between hemodialysis (HD) and peritoneal dialysis (PD) patients. We further investigated the effectiveness of icodextrin in reducing the risk of new-onset diabetes in PD patients. Methods: From the Taiwan health insurance database, 36 879 incident HD patients and 6382 incident PD patients from 2000 to 2010 were identified as study cohorts. We further selected an additional HD cohort matched by propensity scores (PSs) of PD patients. Incidence rates and hazard ratios (HRs) of new-onset diabetes were assessed among cohorts and between icodextrin users and nonusers by the end of 2011. Results: For the unmatched cohorts, the incidence of new-onset diabetes was higher in PD patients than in HD patients (9.16 versus 8.18 per 1000 person-years), with an adjusted HR of 1.51 (95% CI 1.30-1.75) for PD patients. For the PS-matched cohorts, the corresponding incidence rates were 9.43 and 5.90 per 1000 person-years, respectively, with an adjusted HR of 1.61 (95% CI 1.32 1.97). Among PD patients, the incidence was lower in icodextrin users than in nonusers (6.22 versus 12.1 per 1000 person-years), with an adjusted HR of 0.66 (95% CI 0.50-0.88) for users. Conclusions: Our study suggests that PD patients are at a higher risk of developing new-onset diabetes than HD patients. Icodextrin is recommended for PD patients to reduce the risk of new-onset diabetes. PMID- 28992135 TI - Auxin Response Factors: output control in auxin biology. AB - The phytohormone auxin is involved in almost all developmental processes in land plants. Most, if not all, of these processes are mediated by changes in gene expression. Auxin acts on gene expression through a short nuclear pathway that converges upon the activation of a family of DNA-binding transcription factors. These AUXIN RESPONSE FACTORS (ARFs) are thus the effector of auxin response and translate the chemical signal into the regulation of a defined set of genes. Given the limited number of dedicated components in auxin signaling, distinct properties among the ARF family probably contribute to the establishment of multiple unique auxin responses in plant development. In the two decades following the identification of the first ARF in Arabidopsis, much has been learnt about how these transcription factors act, and how they generate unique auxin responses. Progress in genetics, biochemistry, genomics, and structural biology has helped to develop mechanistic models for ARF action. However, despite intensive efforts, many central questions are yet to be addressed. In this review, we highlight what has been learnt about ARF transcription factors, and identify outstanding questions and challenges for the near future. PMID- 28992133 TI - Intestinal Carriage of Third-Generation Cephalosporin-Resistant and Extended Spectrum beta-Lactamase-Producing Enterobacteriaceae in Healthy US Children. AB - Background: The epidemiology of antibiotic-resistant Enterobacteriaceae intestinal carriage in healthy US children has not been well characterized. Methods: Children between 14 days and 14 years of age were enrolled during well child visits in Oakland, California, Kansas City, Kansas, and Nashville, Tennessee, between December 2013 and March 2015. Data on recent antibiotic use by the child and travel and hospitalization history of all members of each child's household were obtained with a risk-factor survey. Stool specimens collected from the subjects were screened for extended-spectrum beta-lactamase-producing (ESBL P) bacteria using CHROMagar ESBL medium. Putative ESBL-P Escherichia coli and Klebsiella colonies underwent phenotypic confirmation by double-disk synergy testing; confirmed third-generation cephalosporin-resistant (3GCR) isolates underwent additional antibiotic-susceptibility testing. Results: In 519 subjects, the overall 3GCR Enterobacteriaceae carriage rate was 4.4% (n = 23) and ranged from 3.4% to 5.1% among the study sites. The ESBL-P Enterobacteriaceae carriage rate was 3.5% (n = 18). The rates of 3GCR Enterobacteriaceae carriage was highest in 1 to <2 year olds at 6.5%, and was 5.2% in <5 year-olds vs 1.7% in >=5-year olds (P = .11). 3GCR and ESBL-P Enterobacteriaceae carriage was associated with international travel within the previous year; 11.1% of ESBL-P Enterobacteriaceae carriers reported this history compared with 1.6% of noncarriers (P = .004). No other queried factor was found to increase risk. Of the 24 analyzed 3GCR isolates, 58% were multidrug resistant. Conclusions: The 3GCR Enterobacteriaceae carriage rate exceeds 5% in healthy US children <5 years of age. International travel within the previous year increased the risk of 3GCR and ESBL-P Enterobacteriaceae carriage. In contrast, we found no differences in the rates of hospitalization or recent antibiotic exposure between carriers and noncarriers. Young children, who have the highest prevalence of colonization, might be a sentinel population to study to gain a better understanding of community sources of antibiotic-resistant Enterobacteriaceae. PMID- 28992136 TI - Shaping intercellular channels of plasmodesmata: the structure-to-function missing link. AB - Plasmodesmata (PD) are a hallmark of the plant kingdom and a cornerstone of plant biology and physiology, forming the conduits for the cell-to-cell transfer of proteins, RNA and various metabolites, including hormones. They connect the cytosols and endomembranes of cells, which allows enhanced cell-to-cell communication and synchronization. Because of their unique position as intercellular gateways, they are at the frontline of plant defence and signalling and constitute the battleground for virus replication and spreading. The membranous organization of PD is remarkable, where a tightly furled strand of endoplasmic reticulum comes into close apposition with the plasma membrane, the two connected by spoke-like elements. The role of these structural features is, to date, still not completely understood. Recent data on PD seem to point in an unexpected direction, establishing a close parallel between PD and membrane contact sites and defining plasmodesmal membranes as microdomains. However, the implications of this new viewpoint are not fully understood. Aided by available phylogenetic data, this review attempts to reassess the function of the different elements comprising the PD and the relevance of membrane lipid composition and biophysics in defining specialized microdomains of PD, critical for their function. PMID- 28992137 TI - Molecular identification of chromoblastomycosis clinical isolates in Guangdong. PMID- 28992138 TI - Antifungal susceptibilities to amphotericin B, triazoles and echinocandins of 77 clinical isolates of cryptic Aspergillus species in multicenter surveillance in Korea. AB - We investigated the in vitro antifungal susceptibilities of cryptic Aspergillus species from nine Korean hospitals. Based on the CLSI epidemiological cutoff values, resistance rates to amphotericin B, itraconazole, voriconazole, posaconazole and caspofungin were as follows: A. awamori (34 isolates; all 0%), A. tubingensis (22; 0%, 4.5%, 0%, 0%, and 0%, respectively), A. sydowii (16; 0%, 6.3%, 0%, 0%, and 6.3%), A. lentulus (2; 50%, 0%, 100%, 50%, and 0%), and A. tamarii (2; all 0%). A. calidoustus (one isolate) showed resistance to multiple drugs. Thus, cryptic species identification can be mandatory for clinically important Aspergillus isolates, with their susceptibility data. PMID- 28992139 TI - Concentrations of representative uraemic toxins in a healthy versus non-dialysis chronic kidney disease paediatric population. AB - Background: Chronic kidney disease (CKD) in childhood is poorly explained by routine markers (e.g. urea and creatinine) and is better depicted in adults by other uraemic toxins. This study describes concentrations of representative uraemic toxins in non-dialysis CKD versus healthy children. Methods: In 50 healthy children and 57 children with CKD Stages 1-5 [median estimated glomerular filtration rate 48 (25th-75th percentile 24-71) mL/min/1.73 m2; none on dialysis], serum concentrations of small solutes [symmetric and asymmetric dimethyl-arginine (SDMA and ADMA, respectively)], middle molecules [beta2 microglobuline (beta2M), complement factor D (CfD)] and protein-bound solutes [p cresylglucuronide (pCG), hippuric acid (HA), indole-acetic acid (IAA), indoxyl sulphate (IxS), p-cresyl sulphate (pCS) and 3-carboxy-4-methyl-5-propyl furanpropionic acid (CMPF)] were measured. Concentrations in the CKD group were expressed as z-score relative to controls and matched for age and gender. Results: SDMA, CfD, beta2M, IxS, pCS, IAA, CMPF and HA concentrations were higher in the overall CKD group compared with controls, ranging from 1.7 standard deviations (SD) for IAA and HA to 11.1 SD for SDMA. SDMA, CfD, beta2M, IxS and CMPF in CKD Stages 1-2 with concentrations 4.8, 2.8, 4.5, 1.9 and 1.6 SD higher, respectively. In contrast, pCS, pCG and IAA concentrations were only higher than controls from CKD Stages 3-4 onwards, but only in CKD Stage 5 for ADMA and HA (z score 2.6 and 20.2, respectively). Conclusions: This is the first study to establish reference values for a wide range of uraemic toxins in non-dialysis CKD and healthy children. We observed an accumulation of multiple uraemic toxins, each with a particular retention profile according to the different CKD stages. PMID- 28992140 TI - Inflammation induces osteoclast differentiation from peripheral mononuclear cells in chronic kidney disease patients: crosstalk between the immune and bone systems. AB - Background: Inflammation and immune system alterations contribute to bone damage in many pathologies by inducing the differentiation of osteoclasts (OCs), the bone resorbing cells. This link is largely unexplored in chronic kidney disease (CKD) and haemodialysis (HD) patients, in which reduced renal function is accompanied by an increased inflammatory state and skeletal abnormality. Methods: We used ex vivo culture experiments to investigate the osteoclastogenic potential of peripheral blood mononuclear cells (PBMCs) of CKD and HD patients, focusing on immune cell subsets and inflammatory cytokines such as LIGHT and receptor activator of nuclear factor kappaB ligand (RANKL). Results: We observed spontaneous osteoclastogenesis with a significant increase in OC formation and bone resorbing activity in late-stage CKD and HD patients when compared with early-stage CKD patients and healthy donors, likely due to an increased expression of RANKL and LIGHT (homologous to Lymphotoxins exhibiting Inducible expression and competing with herpes simplex virus Glycoprotein D for herpes virus entry mediator [HVEM], a receptor expressed by T lymphocytes) in PBMCs. Specific inhibition of these cytokines in PBMCs isolated from CKD stages 3b-5 and HD patients induced the reduction of OC formation in vitro. The phenotypic characterization of peripheral blood cells revealed a significant increase of OC precursors (CD14+CD11b+CD51/61+) and CD14+CD16+ monocytes in advanced CKD and HD patients compared with the control group. Conclusions: Our results suggest that circulating inflammatory monocytes from advanced CKD or HD patients trans differentiate into OCs in vitro and play a relevant role in mineral bone disorders and that LIGHT and RANKL represent new potential therapeutic targets in these settings. PMID- 28992141 TI - Metabolic imaging of fatty kidney in diabesity: validation and dietary intervention. AB - Background: Obesity and type 2 diabetes have not only been linked to fatty liver, but also to fatty kidney and chronic kidney disease. Since non-invasive tools are lacking to study fatty kidney in clinical studies, we explored agreement between proton magnetic resonance spectroscopy (1H-MRS) and enzymatic assessment of renal triglyceride content (without and with dietary intervention). We further studied the correlation between fatty kidney and fatty liver. Methods: Triglyceride content in the renal cortex was measured by 1H-MRS on a 7-Tesla scanner in 27 pigs, among which 15 minipigs had been randomized to a 7-month control diet, cafeteria diet (CAF) or CAF with low-dose streptozocin (CAF-S) to induce insulin independent diabetes. Renal biopsies were taken from corresponding MRS-voxel locations. Additionally, liver biopsies were taken and triglyceride content in all biopsies was measured by enzymatic assay. Results: Renal triglyceride content measured by 1H-MRS and enzymatic assay correlated positively (r = 0.86, P < 0.0001). Compared with control diet-fed minipigs, renal triglyceride content was higher in CAF-S-fed minipigs (137 +/- 51 nmol/mg protein, mean +/- standard error of the mean, P < 0.05), but not in CAF-fed minipigs (60 +/- 10 nmol/mg protein) compared with controls (40 +/- 6 nmol/mg protein). Triglyceride contents in liver and kidney biopsies were strongly correlated (r = 0.97, P < 0.001). Conclusions: Non-invasive measurement of renal triglyceride content by 1H-MRS closely predicts triglyceride content as measured enzymatically in biopsies, and fatty kidney appears to develop parallel to fatty liver. 1H-MRS may be a valuable tool to explore the role of fatty kidney in obesity and type 2 diabetic nephropathy in humans in vivo. PMID- 28992142 TI - Researching safety culture: deliberative dialogue with a restorative lens. AB - Safety culture is a key component of patient safety. Many patient safety strategies in health care have been adapted from high-reliability organizations (HRO) such as aviation. However, to date, attempts to transform the cultures of health care settings through HRO approaches have had mixed results. We propose a methodological approach for safety culture research, which integrates the theory and practice of restoration science with the principles and methods of deliberative dialogue to support active engagement in critical reflection and collective debate. Our aim is to describe how these two innovative approaches in health services research can be used together to provide a comprehensive effective method to study and implement change in safety culture. Restorative research in health care integrates socio-ecological theory of complex adaptive systems concepts with collaborative, place-sensitive study of local practice contexts. Deliberative dialogue brings together all stakeholders to collectively develop solutions on an issue to facilitate change. Together these approaches can be used to actively engage people in the study of safety culture to gain a better understanding of its elements. More importantly, we argue that the synergistic use of these approaches offers enhanced potential to move health care professionals towards actionable strategies to improve patient safety within today's complex health care systems. PMID- 28992143 TI - A qualitative study of sign-out processes between primary and on-call residents: relationships in information exchange, responsibility and accountability. AB - Objective: To review a quality improvement event on the process of sign-outs between the primary and on-call residents. Design: A retrospective qualitative study using semi-structured interviews. Setting: A tertiary academic medical center in Singapore with 283 inpatient Medicine beds served by 28 consultants, 29 registrars, 45 residents and 30 interns during the day but 5 residents and 3 interns at night. Participants: Residents, registrars and consultants. Intervention: Quality improvement event on sign-out. Main outcome: Effectiveness of sign-out comprises exchange of patient information, professional responsibility and task accountability. Results: The following process of sign outs was noted. Primary teams were accountable to the on-call resident by selecting at-risk patients and preparing contingency plans for sign-out. Structured information exchanged included patient history, active problems and plans of care. On-call residents took ownership of at-risk patients by actively asking questions during sign-out and reporting back the agreed care plan. On-call residents were accountable to the primary team by reporting back at-risk patients the next day. Conclusion: A structured information exchange at sign-out increased the on-call resident's ability to care for at-risk patients when it was supported by two-way transfers of responsibility and accountability. PMID- 28992144 TI - Hospital survey on patient safety culture (HSOPS): variability of scoring strategies. AB - Objective: To assess the variability of safety culture dimension scores and their associated rankings depending on three different scoring strategies using the Hospital Survey On Patient Safety Culture (HSOPS). Design: Cross-sectional study using a self-administered questionnaire. Setting: The study was conducted in an 1836-bed acute-care French university hospital with an annual volume of 135 999 stays, between April 2013 and November 2014. Participants: All caregivers and technical-administrative staff with at least 6 months of employment, spending at least half of their working time in the hospital, were asked to participate. Intervention: None. Main outcome measure: The variability of the HSOPS results using three different scoring methods: the percentage of positive responses recommended by the Agency for Healthcare Research and Quality, the averaged individual means and the averaged individual sums. Results: The response rate was 78.6% (n = 3978). The percentage of positive responses resulted in lower scores compared to averaged individual means and averaged individual sums in the six least developed dimensions, and gave more widely spread scores and greater 95CIs in the six most developed dimensions. Department rankings also varied greatly depending on the scoring methods. Conclusion: The values of the HSOPS scores and their corresponding rankings greatly depended on the computation method. This finding shows how important it is to agree on the use of the same scoring strategies, before broadly comparing results within and across organizations. PMID- 28992145 TI - Burnout syndrome among non-consultant hospital doctors in Ireland: relationship with self-reported patient care. AB - Objective: Intensive workload and limited training opportunities for Irish non consultant hospital doctors (NCHDs) has a negative effect on their health and well-being, and can result in burnout. Burnout affects physician performance and can lead to medical errors. This study examined the prevalence of burnout syndrome among Irish NCHDs and its association with self-reported medical error and poor quality of patient care. Methods: A cross-sectional quantitative survey based design. Setting: All teaching hospitals affiliated with University College Cork. Participants: NCHDs of all grades and specialties. Intervention(s): The following instruments were completed by all participants: Maslach Burnout Inventory-Human Service Survey (MBI-HSS), assessing three categories of burnout syndrome: Emotional exhaustion (EE), Personal Achievement (PA) and Depersonalization (DP); questions related to self-reported medical errors/poor patient care quality and socio-demographic information. Main outcome measure(s): Self-reported measures of burnout and poor quality of patient care. Results: Prevalence of burnout among physicians (n = 265) was 26.4%. There was a significant gender difference for EE and DP, but none for PA. A positive weak correlation was observed between EE and DP with medical error or poor patient care. A negative association was reported between PA and medical error and reduced quality of patient care. Conclusions: Burnout is prevalent among NCHDs in Ireland. Burnout syndrome is associated with self-reported medical error and quality of care in this sample population. Measures need to be taken to address this issue, with a view to protecting health of NCHDs and maintaining quality of patient care. PMID- 28992146 TI - Conceptualizing and assessing improvement capability: a review. AB - Purpose: The literature is reviewed to examine how 'improvement capability' is conceptualized and assessed and to identify future areas for research. Data sources: An iterative and systematic search of the literature was carried out across all sectors including healthcare. The search was limited to literature written in English. Data extraction: The study identifies and analyses 70 instruments and frameworks for assessing or measuring improvement capability. Information about the source of the instruments, the sectors in which they were developed or used, the measurement constructs or domains they employ, and how they were tested was extracted. Results of data synthesis: The instruments and framework constructs are very heterogeneous, demonstrating the ambiguity of improvement capability as a concept, and the difficulties involved in its operationalisation. Two-thirds of the instruments and frameworks have been subject to tests of reliability and half to tests of validity. Many instruments have little apparent theoretical basis and do not seem to have been used widely. Conclusion: The assessment and development of improvement capability needs clearer and more consistent conceptual and terminological definition, used consistently across disciplines and sectors. There is scope to learn from existing instruments and frameworks, and this study proposes a synthetic framework of eight dimensions of improvement capability. Future instruments need robust testing for reliability and validity. This study contributes to practice and research by presenting the first review of the literature on improvement capability across all sectors including healthcare. PMID- 28992147 TI - The degree of severity and trends in hospital standardized mortality ratios in Japan between 2008 and 2012: a retrospective observational study. AB - Objectives: Hospital standardized mortality ratio (HSMR), an indicator that adjusts hospital mortality for case-mix differences, is used as a hospital performance measure. The aim of this study is to build a new HSMR model in Japan and examine HSMR trends according to the degree of severity. Design: Observational retrospective study. Settings: Data from the Japanese Administrative Database. Participants: A total of 3 813 492 admissions from 278 Japanese acute-care hospitals were extracted from the database (patients between 2008 and 2012, from July to December in each year). Main Outcome Measures: We estimated the probability of in-hospital death by fitting a logistic regression model, and assessed the performance of the models with the c-index. In each year, HSMRs were obtained by calculating the ratio of the number of observed deaths to the number of expected deaths. The HSMR trends, including trends in comorbidity subgroups defined by the Charlson comorbidity index, were analysed. Results: The c-index value was 0.871 for the HSMR model. The HSMR followed a constant decreasing trend over time; it fell by 18.8% from 110.3 in 2008 to 91.5 in 2012. The reduction in HSMR was not present in the severe comorbidity group, while the reduction trend was observed in the mild comorbidity group. Conclusions: Our model demonstrated excellent discrimination without detailed clinical data. The Japanese HSMR followed a constant decreased trend, while the reduction trend was not present in the severe patients. Our study implies the need to consider severe patients for assessing hospital quality by HSMR. PMID- 28992148 TI - Inappropriate hospital days of a tertiary hospital in Shanghai, China. AB - Objective: This study aims to evaluate the prevalence of inappropriate hospital stays in a tertiary hospital in Shanghai, identify the causes for the inappropriateness and analyze the predictors. Design: A retrospective review of medical records. Setting: The cardiology and the orthopedics departments of a tertiary hospital in Shanghai, China. Participants: About 806 patients discharged from the cardiology or the orthopedics department of a tertiary hospital from March 2013 to February 2014. Interventions: Two reviewers audited 8396 hospital days of the cardiology department (n = 3606) and the orthopedics department (n = 4790) by adopting the Chinese Version of the Appropriateness Evaluation Protocol. Univariate and multivariate analysis were adopted to identify the predictors of higher levels of inappropriateness produced by internal causes. Main outcome measure: The prevalence of inappropriate hospital days. Results: It was found that 910 (25.2%) and 1940 (40.5%) hospital days were judged to be inappropriate in the cardiology and the orthopedics departments, respectively; and 753 (20.9%) and 1585 (33.1%) of these inappropriate hospital days were due to internal reasons, respectively. Awaiting tests, surgery or discharge were determined to constitute the main causes of inappropriateness for both departments. The predictors of higher levels of inappropriateness in the cardiology department were younger age, self-pay, outpatient admission and inappropriate admission. Self-pay, surgical and/or first-time admission patients exhibited the highest levels of inappropriateness in the orthopedics department. Conclusions: The rates of inappropriateness in the involved departments were relatively high. Further interventions should be designed and implemented, accordingly. PMID- 28992149 TI - Using an online quiz-based reinforcement system to teach healthcare quality and patient safety and care transitions at the University of California. AB - Quality issue: Implementing quality improvement (QI) education during clinical training is challenging due to time constraints and inadequate faculty development in these areas. Initial assessment: Quiz-based reinforcement systems show promise in fostering active engagement, collaboration, healthy competition and real-time formative feedback, although further research on their effectiveness is required. Choice of solution: An online quiz-based reinforcement system to increase resident and faculty knowledge in QI, patient safety and care transitions. Implementation: Experts in QI and educational assessment at the 5 University of California medical campuses developed a course comprised of 3 quizzes on Introduction to QI, Patient Safety and Care Transitions. Each quiz contained 20 questions and utilized an online educational quiz-based reinforcement system that leveraged spaced learning. Evaluation: Approximately 500 learners completed the course (completion rate 66-86%). Knowledge acquisition scores for all quizzes increased after completion: Introduction to QI (35-73%), Patient Safety (58-95%), and Care Transitions (66-90%). Learners reported that the quiz-based system was an effective teaching modality and preferred this type of education to classroom-based lectures. Suggestions for improvement included reducing frequency of presentation of questions and utilizing more questions that test learners on application of knowledge instead of knowledge acquisition. Lessons learned: A multi-campus online quiz-based reinforcement system to train residents in QI, patient safety and care transitions was feasible, acceptable, and increased knowledge. The course may be best utilized to supplement classroom based and experiential curricula, along with increased attention to optimizing frequency of presentation of questions and enhancing application skills. PMID- 28992150 TI - Are children presenting with non-IMCI complaints at greater risk for suboptimal screening? An analysis of outpatient visits in Afghanistan. AB - Objective: To determine if children presenting without complaints related to the Integrated Management of Childhood Illness (IMCI) are at greater risk for suboptimal screening for IMCI conditions. Design: Cross-sectional study. Setting: Thirty-three provinces in Afghanistan. Participants: Observation of 3072 sick child visits selected by systematic random sampling. Main outcome measure(s): A 10 point IMCI assessment index. Results: One hundred and thirty-one (4.3%) of the 3072 sick child visits involved no IMCI-related complaints. The mean assessment index for all sick child visits was 4.81 (SD 2.41). Visits involving any IMCI related complaint were associated with a 1.02 point higher mean assessment index than those without IMCI-related complaints (95% CI, 0.52-1.53; P < 0.001). After adjusting for relevant covariates including patient age, caretaker gender, provider type, provider gender, provider IMCI training status and IMCI guideline availability, we found that children with IMCI-related presenting complaints had a significantly better quality of IMCI screening, than those without IMCI presenting complaints (by 0.75 points; 95% CI, 0.25-1.26; P = 0.003). Conclusions: Our study indicates that children with non-IMCI presenting complaints are at greater risk of suboptimal screening compared to children with IMCI-related presenting complaints. The premise of IMCI is to routinely screen all children for conditions responsible for the major burden of childhood disease in countries like Afghanistan. The study illustrates an important finding that facility and provider capacity needs to be improved, particularly during training, supervision and guideline dissemination to ensure that all children receive routine screening for common IMCI conditions. PMID- 28992152 TI - Evaluating the impact of accreditation on Brazilian healthcare organizations: A quantitative study. AB - Objective: The aim of this study was to evaluate the impact of accreditation programs on Brazilian healthcare organizations. Design: A web-based questionnaire survey was undertaken between February and May 2016. Setting: Healthcare organizations from the Federal District and from 18 Brazilian states. Participants: The quality managers of 141 Brazilian healthcare organizations were the main respondents of the study. Intervention: The questionnaire was applied to not accredited and accredited organizations. Main Outcome Measures: The main outcome measures were patient safety activities, quality management activities, planning activities-policies and strategies, patient involvement, involvement of professionals in the quality programs, monitoring of patient safety goals, organizational impact and financial impacts. Results: The study identified 13 organizational impacts of accreditation. There was evidence of a significant and moderate correlation between the status of accreditation and patient safety activities, quality management activities, planning activities-policies and strategies, and involvement of professionals in the quality programs. The correlation between accreditation status and patient involvement was significant but weak, suggesting that this issue should be treated with a specific policy. The impact of accreditation on the financial results was not confirmed as relevant; however, the need for investment in the planning stage was validated. Conclusions: The impact of accreditation is mainly related to internal processes, culture, training, institutional image and competitive differentiation. PMID- 28992151 TI - A comparison of in-hospital acute myocardial infarction management between Portugal and the United States: 2000-2010. AB - Objective: To compare healthcare in acute myocardial infarction (AMI) treatment between contrasting health systems using comparable representative data from Europe and USA. Design: Repeated cross-sectional retrospective cohort study. Setting: Acute care hospitals in Portugal and USA during 2000-2010. Participants: Adults discharged with AMI. Interventions: Coronary revascularizations procedures (percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) surgery). Main Outcome Measures: In-hospital mortality and length of stay. Results: We identified 1 566 601 AMI hospitalizations. Relative to the USA, more hospitalizations in Portugal presented with elevated ST-segment, and fewer had documented comorbidities. Age-sex-adjusted AMI hospitalization rates decreased in USA but increased in Portugal. Crude procedure rates were generally lower in Portugal (PCI: 44% vs. 47%; CABG: 2% vs. 9%, 2010) but only CABG rates differed significantly after standardization. PCI use increased annually in both countries but CABG decreased only in the USA (USA: 0.95 [0.94, 0.95], Portugal: 1.04 [1.02, 1.07], odds ratios). Both countries observed annual decreases in risk-adjusted mortality (USA: 0.97 [0.965, 0.969]; Portugal: 0.99 [0.979, 0.991], hazard ratios). While between-hospital variability in procedure use was larger in USA, the risk of dying in a high relative to a low mortality hospital (hospitals in percentiles 95 and 5) was 2.65 in Portugal when in USA was only 1.03. Conclusions: Although in-hospital mortality due to an AMI improved in both countries, patient management in USA seems more effective and alarming disparities in quality of care across hospitals are more likely to exist in Portugal. PMID- 28992153 TI - Reporting of medication administration errors by nurses in South Korean hospitals. AB - Objective: To identify differences in what nurses consider as medication administration errors, to examine their willingness to report these errors and to identify barriers to reporting medication errors by hospital type. Design: Cross sectional, descriptive design. The questionnaire comprised six medication administration error scenarios and items related to the reasons for not reporting medication errors. Setting: Two tertiary and three general hospitals in a metropolitan area, and five general hospitals in K province, in South Korea. Participants: Registered nurses working at tertiary and general hospitals in South Korea (n = 467). Main outcome measures: Consideration of medication administration errors, intention to report medication errors and reasoning for not file an incident report. Results: There were no significant differences in what nurses considered as medication administration errors between nurses working different in hospital types. The rate of incident reporting was very low; it ranged from 6.3% to 29.9%, regardless of hospital type. Korean nurses were more likely to report an error to a physician than file an incident report. The primary reason for not reporting medication errors was fear of the negative consequences of reporting the error and subsequent legal action. Conclusions: The rate of filing an incident report among nurses was very low, regardless of hospital type or whether nurses perceived the incident as a medication administration error. These results may have significant implications for improving medication safety in hospitals, and more efforts are needed at the organizational level to improve incident reporting by nurses. PMID- 28992154 TI - The patient-centered medical home: a reality for HIV care in Nigeria. AB - Objective: HIV care delivery in resource-limited settings (RLS) may serve as a paradigm for chronic disease care, but comprehensive measurement frameworks are lacking. Our objective was to adapt the patient-centered medical home (PCMH) framework for use in RLS, and evaluate the performance of HIV treatment programs within this framework. Design and setting: Cross-sectional survey administered within the AIDS Prevention Initiative in Nigeria (APIN) network. Participants: Medical directors at APIN clinics. Main outcome measures: We adapted the 2011 US National Committee on Quality Assurance's PCMH standard to develop a survey measuring five domains of HIV care: (i) enhancing access and continuity, (ii) identifying and managing patient populations, (iii) planning and managing care, (iv) promoting self-care and support and (v) measuring and improving performance. Results: Thirty-three of 36 clinics completed the survey. Most were public (73%) and urban/semi-urban (64%); 52% had >500 patients in care. On a 0-100 scale, clinics scored highest in self-care and support, 91% (63-100%); managing patient populations, 80% (72-81%) and improving performance, 72% (44-78%). Clinics scored lowest with the most variability in planning/managing care, 65% (22-89%), and access and continuity, 61% (33-80%). Average score across all domains was 72% (58 81%). Conclusions: Our findings suggest that the modified PCMH tool is feasible, and likely has sufficient performance variation to discriminate among clinics. Consistent with extant literature, clinics showed greatest room for improvement on access and continuity, supporting the tool's face validity. The modified PCMH tool may provide a powerful framework for evaluating chronic HIV care in RLS. PMID- 28992155 TI - Attitudes towards accreditation among hospital employees in Denmark: a cross sectional survey. AB - Objective: To evaluate attitudes towards accreditation and the Danish Quality Model (DDKM) among hospital employees in Denmark. Negative attitudes led the Danish Government to abolish accreditation in 2015. Design: A cross-sectional survey was carried out via web-based questionnaire. Setting: All hospital managers, quality improvement staff (quality managers and employees), and hospital surveyors in Denmark; and clinicians (doctors and nurses) within nine selected specialties. Participants: Overall response rate was 29% with 5055 of 17 646 valid responses included in the data analysis. The response rate was 82% (5055/6188) among respondents who clicked on the link in the mail containing the questionnaire. Methods: A short questionnaire was designed using a 7-point Likert scale ranging from 1 'strongly disagree' to 7 'strongly agree'. To compare mean values between respondent groups, regression analysis using dummy coding of respondent groups and calculation of standardized mean difference effect sizes were performed. Results: Overall attitudes were supportive, with physicians more skeptical. There were different patterns of attitudes in the five Danish regions and between medical professions. A small group of physicians was extremely negative. Conclusion: Clinical attitudes are important, and can affect Government decisions. On the basis of our study, future attention should be paid to attitudes towards accreditation (and attitudes towards other means of quality improvement). Attitudes may reflect political agendas and impede the take-up of improvement programs, cause their demise, or reduce their effectiveness. PMID- 28992157 TI - A multi-state, multi-site, multi-sector healthcare improvement model: implementing evidence for practice. AB - Quality problem or issue: Healthcare is complex and we know that evidence takes nearly 20 years to find its way into clinical practice. Initial assessment: The slow process of translating research points to the need for effective translational research models to ensure patient care quality and safety are not compromised by such an epistemic failure. Choice of solution: Our model to achieve reasonably rapid and enduring improvements to clinical care draws on that developed and promulgated by the Institute for Healthcare Improvement in the United States of America model as well as that developed by the Johns Hopkins Quality and Safety Group known as the Translating Research into Practice implementation model. Implementation: The core principle of our hybrid model was to engage those most likely to be affected by the changes being introduced through a series of face-to-face and web-enabled meetings that act both as drivers of information but also as a means of engaging all stakeholders across the healthcare system involved in the change towards their pre-established goals. Evaluation: The model was piloted on the focused topic of the management of inadvertent perioperative hypothermia across nine hospitals within Australia (four sites in Victoria, three sites in New South Wales and two sites in Queensland). Improvement in management of hypothermia in these patients was achieved and sustained over time. Lessons learned: Our model aims to engage the hearts and minds of healthcare clinicians, and others in order to empower them to make the necessary improvements to enhance patient care quality and safety. PMID- 28992158 TI - Avoidable emergency department visits: a starting point. AB - Objective: To better characterize and understand the nature of a very conservative definition of 'avoidable' emergency department (ED) visits in the United States to provide policymakers insight into what interventions can target non-urgent ED visits. Design/setting: We performed a retrospective analysis of a very conservative definition of 'avoidable' ED visits using data from the National Hospital Ambulatory Medical Care Survey from 2005 to 2011. Participants: We examined a total of 115 081 records, representing 424 million ED visits made by patients aged 18-64 years who were seen in the ED and discharged home. Main outcome measures: We defined 'avoidable' as ED visits that did not require any diagnostic or screening services, procedures or medications, and were discharged home. Results: In total, 3.3% (95% CI: 3.0-3.7) of all ED visits were 'avoidable.' The top five chief complaints included toothache, back pain, headache, other symptoms/problems related to psychosis and throat soreness. Alcohol abuse, dental disorders and depressive disorders were among the top three ICD-9 discharge diagnoses. Alcohol-related disorders and mood disorders accounted for 6.8% (95% CI: 5.7-8.0) of avoidable visits, and dental disorders accounted for 3.9% (95% CI: 3.0-4.8) of CCS-grouped discharge diagnoses. Conclusions: A significant number of 'avoidable' ED visits were for mental health and dental conditions, which the ED is not fully equipped to treat. Our findings provide a better understanding of what policy initiatives could potentially reduce these 'avoidable' ED visits to address the gaps in our healthcare system, such as increased access to mental health and dental care. PMID- 28992156 TI - What works in implementation of integrated care programs for older adults with complex needs? A realist review. AB - Purpose: A realist review of the evaluative evidence was conducted on integrated care (IC) programs for older adults to identify key processes that lead to the success or failure of these programs in achieving outcomes such as reduced healthcare utilization, improved patient health, and improved patient and caregiver experience. Data sources: International academic literature was searched in 12 indexed, electronic databases and gray literature through internet searches, to identify evaluative studies. Study selection: Inclusion criteria included evaluative literature on integrated, long-stay health and social care programs, published between January 1980 and July 2015, in English. Data extraction: Data were extracted on the study purpose, period, setting, design, population, sample size, outcomes, and study results, as well as explanations of mechanisms and contextual factors influencing outcomes. Results of data synthesis: A total of 65 articles, representing 28 IC programs, were included in the review. Two context-mechanism-outcome configurations (CMOcs) were identified: (i) trusting multidisciplinary team relationships and (ii) provider commitment to and understanding of the model. Contextual factors such as strong leadership that sets clear goals and establishes an organizational culture in support of the program, along with joint governance structures, supported team collaboration and subsequent successful implementation. Furthermore, time to build an infrastructure to implement and flexibility in implementation, emerged as key processes instrumental to success of these programs. Conclusions: This review included a wide range of international evidence, and identified key processes for successful implementation of IC programs that should be considered by program planners, leaders and evaluators. PMID- 28992159 TI - Compliance with accreditation and recommended hospital care-a Danish nationwide population-based study. AB - Objective: To examine the association between compliance with accreditation and recommended hospital care. Design: A Danish nationwide population-based follow-up study based on data from six national, clinical quality registries between November 2009 and December 2012. Setting: Public, non-psychiatric Danish hospitals. Participants: Patients with acute stroke, chronic obstructive pulmonary disease, diabetes, heart failure, hip fracture and bleeding/perforated ulcers. Interventions: All hospitals were accredited by the first version of The Danish Healthcare Quality Programme. Compliance with accreditation was defined by level of accreditation awarded the hospital after an announced onsite survey; hence, hospitals were either fully (n = 11) or partially accredited (n = 20). Main Outcome Measures: Recommended hospital care included 48 process performance measures reflecting recommendations from clinical guidelines. We assessed recommended hospital care as fulfilment of the measures individually and as an all-or-none composite score. Results: In total 449 248 processes of care were included corresponding to 68 780 patient pathways. Patients at fully accredited hospitals had a significantly higher probability of receiving care according to clinical guideline recommendations than patients at partially accredited hospitals across conditions (individual measure: adjusted odds ratio (OR) = 1.20, 95% CI: 1.01-1.43, all-or-none: adjusted OR = 1.27, 95% CI: 1.02-1.58). For five of the six included conditions there were an association; the pattern appeared particular strong among patients with acute stroke and hip fracture (all-or-none; acute stroke: adjusted OR = 1.39, 95% CI: 1.05-1.83, hip fracture: adjusted OR = 1.57, 95% CI: 1.00-2.49). Conclusion: High compliance with accreditation standards was associated with a higher level of evidence-based hospital care in Danish hospitals. PMID- 28992160 TI - Physicians' and pharmacists' perceptions on real-time drug utilization review system: a nationwide survey. AB - Objective: To identify healthcare providers' experience and satisfaction for the drug utilization review (DUR) system, their impact on prescription changes following alerts, and difficulties experienced in the system by surveying primary healthcare centers and pharmacies. Design: A cross-sectional nationwide survey. Setting and participants: Approximately 2000 institutions were selected for the survey by a simple random sampling of nationwide primary healthcare centers and community pharmacy approximately practices, and 358 replied. Main outcomes measures: The questionnaire included questions on experience and recognition of DUR alerts, personal attitude and respondents' biographical information. Space was included for respondents to suggest improvements of the DUR system. Results: The DUR system scored 71.5 out of 100 points for satisfaction by physicians and pharmacists, who reported that the alerts prevent medication-related errors; most respondents (96.6%) received the alerts. Several respondents (10.9%) replied that they prescribe or dispense prescriptions as they are without following the alerts. Physicians (adjusted odds ratio, 8.334; 95% confidence interval, 3.449 20.139) are more likely to change the prescription than pharmacists and persons with alert experience (4.605; 1.080-19.638). However, current practice in metropolitan areas (0.478; 0.228-1.000) and frequent alerts regarding co administration incompatibilities within prescriptions (0.135; 0.031-0.589) negatively influence adherence to DUR alerts. Conclusions: Although most surveyed physicians and pharmacists receive the alerts, some do not or reported that they would not follow the alerts. To increase adherence, the DUR system should be improved to ensure a preferential and intensive approach to detecting potentially high-risk drug combinations. PMID- 28992162 TI - Healthcare quality improvements through hospital accreditation compliance and effective procedure use. PMID- 28992161 TI - The role of patient perception of crowding in the determination of real-time patient satisfaction at Emergency Department. AB - Objective: To evaluate the associations between real-time overall patient satisfaction and Emergency Department (ED) crowding as determined by patient percepton and crowding estimation tool score in a high-volume ED. Design: A prospective observational study. Setting: A tertiary acute hospital ED and a Level 1 trauma center. Participants: ED patients. Intervention(s): Crowding status was measured by two crowding tools [National Emergency Department Overcrowding Scale (NEDOCS) and Severely overcrowded-Overcrowded-Not overcrowded Estimation Tool (SONET)] and patient perception of crowding surveys administered at discharge. Main outcome measure(s): ED crowding and patient real-time satisfaction. Results: From 29 November 2015 through 11 January 2016, we enrolled 1345 participants. We observed considerable agreement between the NEDOCS and SONET assessment of ED crowding (bias = 0.22; 95% limits of agreement (LOAs): 1.67, 2.12). However, agreement was more variable between patient perceptions of ED crowding with NEDOCS (bias = 0.62; 95% LOA: -5.85, 7.09) and SONET (bias = 0.40; 95% LOA: -5.81, 6.61). Compared to not overcrowded, there were overall inverse associations between ED overcrowding and patient satisfaction (Patient perception OR = 0.49, 95% confidence limit (CL): 0.38, 0.63; NEDOCS OR = 0.78, 95% CL: 0.65, 0.95; SONET OR = 0.82, 95% CL: 0.69, 0.98). Conclusions: While heterogeneity exists in the degree of agreement between objective and patient perceived assessments of ED crowding, in our study we observed that higher degrees of ED crowding at admission might be associated with lower real-time patient satisfaction. PMID- 28992164 TI - Functional disability and other health-related quality-of-life domains: points to consider for clinical trials in systemic sclerosis. AB - Patients with SSc have the highest mortality among the rheumatic diseases. In addition, SSc is associated with disfigurement, hand contractures, fatigue, poor sleep, severe RP with numbness and tingling of the fingers can lead to decrements in quality of life. This Points to Consider article provides practical considerations for design of trials for functional disability and other health related quality-of-life issues. PMID- 28992165 TI - Points to consider for designing trials in systemic sclerosis patients with arthritic involvement. AB - Although musculoskeletal involvement is quite common in SSc (arthritic in particular), there have been few trials and even fewer controlled trials of therapeutic agents in arthritis in SSc. In addition, there have been only three outcome measures that have been validated for use in trials of SSc arthritis: the HAQ Disability Index, the Cochin Hand Function Scale and the Hand Mobility in SSc scale. The purpose of this article is to present evidence-based points to consider for the design of trials in SSc patients with musculoskeletal involvement (joints in particular). In addition, we make an argument for including outcome variables that can be validated within a given trial for use in future trials. PMID- 28992163 TI - Pak1 mediates the stimulatory effect of insulin and curcumin on hepatic ChREBP expression. AB - Insulin can stimulate hepatic expression of carbohydrate-responsive element binding protein (ChREBP). As recent studies revealed potential metabolic beneficial effects of ChREBP, we asked whether its expression can also be regulated by the dietary polyphenol curcumin. We also aimed to determine mechanisms underlying ChREBP stimulation by insulin and curcumin. The effect of insulin on ChREBP expression was assessed in mouse hepatocytes, while the effect of curcumin was assessed in mouse hepatocytes and with curcumin gavage in mice. Chemical inhibitors for insulin signaling molecules were utilized to identify involved signaling molecules, and the involvement of p21-activated protein kinase 1 (Pak1) was determined with its chemical inhibitor and Pak1-/- hepatocytes. We found that both insulin and curcumin-stimulated ChREBP expression in Akt independent but MEK/ERK-dependent manner, involving the inactivation of the transcriptional repressor Oct-1. Aged Pak1-/- mice showed reduced body fat volume. Pak1 inhibition or its genetic deletion attenuated the stimulatory effect of insulin or curcumin on ChREBP expression. Our study hence suggests the existence of a novel signaling cascade Pak1/MEK/ERK/Oct-1 for both insulin and curcumin in exerting their glucose-lowering effect via promoting hepatic ChREBP production, supports the recognition of beneficial functions of ChREBP, and brings us a new overview on dietary polyphenols. PMID- 28992166 TI - Points to consider for clinical trials of the gastrointestinal tract in systemic sclerosis. AB - The pathogenesis of gastrointestinal tract involvement in SSc is not fully understood. However, gastrointestinal signs and symptoms are very common. Trials to test therapies, with rare exceptions, should be double-blind, randomized trials with either active therapy or placebo as comparators. Trial duration will vary dependent on the anticipated therapy and should usually be 6-24 weeks long, although some motility trials may need to be 52 weeks. As in any well-controlled trial, inclusion and exclusion criteria should encourage relatively uniform patients with sufficiently active disease to discern response, importantly considering disease duration. Previous therapy, co-morbid conditions, potentially confounding and/or concomitant therapy should be considered. Outcome measures should include both objective/semi-objective and subjective measures, although validated measures are not frequent and design needs to consider using only validated measures. Unvalidated measures can be included to validate them for future use. A full analysis plan should be completed before study commencement, including the method to account for missing data. PMID- 28992167 TI - Muscle involvement in systemic sclerosis: points to consider in clinical trials. AB - SSc is clinically and pathogenetically heterogeneous. Consensus standards for trial design and outcome measures are needed. International experts experienced in SSc clinical trial design and a researcher experienced in systematic literature review screened the PubMed and Cochrane Central Register of Controlled Trials in order to develop points to consider when planning a clinical trial for muscle involvement in SSc. The experts conclude that SSc-associated muscle involvement is heterogeneous and lacks a universally accepted gold-standard for measuring therapeutic response. Although outcome studies are currently limited by the inability to clearly distinguish active, reversible muscle inflammation from irreversible muscle damage and extramuscular organ involvement, strong consideration should be given to enrolling patients with a myopathy that features several elements of likely reversibility such as muscle weakness, biopsy-proven active inflammation, an MRI indicating muscle inflammation and a baseline serum creatinine kinase above three times the upper limit of normal to prevent floor effect. Randomized controlled trials are preferred, with a duration of at least 24 weeks. Outcome measures should include a combination of elements that are likely to be reversible, such as muscle weakness, biopsy-proven active inflammation, creatinine kinase/aldolase and a quality of life questionnaire. The individual measurements might require a short pre-study for further validation. A biological sample repository is recommended. PMID- 28992168 TI - Pulmonary hypertension related to systemic sclerosis: points to consider for clinical trials. AB - There are proven successful approaches to clinical trial design in pulmonary arterial hypertension (PAH), which in turn have led to the licensing of a number of effective therapies. SSc has been included in trials of World Health Organization Group 1 PAH but has been under-represented. Responses in outcomes as diverse as exercise capacity, quality of life, durability of drug effect and survival have been reduced in comparison with those seen in idiopathic PAH. The PAH community has achieved international and interdisciplinary consensus guidelines for future studies. We consider the diverse outcome measures used in trials in the context of the complexities of scleroderma. An argument is advanced in favour of future trials focused exclusively on SSc but with adaptations of the core outcome measures and trial design templates applicable to more general studies of PAH. PMID- 28992169 TI - Points to consider when doing a trial primarily involving the heart. AB - Cardiac involvement contributes to the severity of SSc and should carefully be investigated and managed in SSc patients. Although it is commonly sub-clinical, once symptomatic it has a poor prognosis. Several complementary tools (circulating biomarkers, electrocardiography, echocardiography, scintigraphy or MRI) allow the assessment of all the various cardiac structures (endocardium, myocardium and pericardium) and heart function. Treatment remains empirical but cardiac trials in SSc can add data to the treatment of this complication. PMID- 28992170 TI - Points to consider-Raynaud's phenomenon in systemic sclerosis. AB - RP is an exaggerated vasospastic response to cold or emotion. Randomized, double blind, placebo-controlled trials with either parallel group or cross-over trials should be mainly considered. Cross-over design, which is good for early phase trials of immediate or very short-term outcomes, is important in a condition as heterogeneous as RP: a wash-out period between treatment arms should always be included to minimize the possibility of a period (carry-over) effect. Duration of RP trials is usually constrained by the need to complete these over a single season, usually winter when the weather is colder. For cross-over trials, each treatment arm tends to be 4 weeks or less. Frequency and duration of attacks, and the Raynaud's Condition Score are widely used outcome measures. There is increasing interest in physiological laboratory endpoints, for example laser Doppler imaging at least for early phase trials. PMID- 28992171 TI - Points to consider for skin ulcers in systemic sclerosis. AB - This article discusses points to consider when undertaking a clinical trial to test therapy for skin ulcers in SSc. A validated definition of skin ulcers should be used if available. Defining a uniform SSc patient population, including consideration of disease duration, history of digital ulcers and capillaroscopic patterns, is important. Excluding confounding factors such as infection, calcinosis and trauma should be strongly considered, or at least accounted for, in defining patients. Outcome measures such as time to healing, prevention of new ulcers, function, pain and objective measures such as US, laser Doppler and thermography can be considered as outcome measures, although their validation has not yet been achieved and efforts may be needed to validate them before use. Likewise, biomarkers should be considered or consideration should be given to storing serum, plasma or cells for possible future analysis. A pre-planned analysis is important and should include consideration of missing data. PMID- 28992172 TI - Points to consider in renal involvement in systemic sclerosis. AB - This article discusses points to consider when undertaking a clinical trial to test therapy for renal involvement in SSc, not including scleroderma renal crisis. Double-blind, randomized controlled trials vs placebo or standard background therapy should be strongly considered. Inclusion criteria should consider a pre-specified range of renal functions or stratification of renal function. Gender and age limitations are probably not necessary. Concomitant medications including vasodilators, immunosuppressants and endothelin receptor antagonists and confounding illnesses such as diabetes, kidney stones, hypertension and heart failure need to be considered. A measure of renal function should be strongly considered, while time to dialysis, mortality, prevention of scleroderma renal crisis and progression of renal disease can also be considered, although they remain to be validated. Detailed, pre-planned analysis should be strongly considered and should include accounting for missing data. PMID- 28992175 TI - Trial methodology in scleroderma: Avoiding a shot in the dark. PMID- 28992173 TI - Assessment of skin involvement in systemic sclerosis. AB - Skin involvement in SSc is an important marker of disease activity, severity and prognosis, making the assessment of skin a key issue in SSc clinical research. We reviewed the published data assessing skin involvement in clinical trials and summarized the major conclusions important in SSc clinical research. A systematic literature review identified randomized controlled trials using skin outcomes in SSc. Analysis examined the validity of the different skin measures based on literature findings. Twenty-two randomized controlled trials were found. The average study duration was 10.2 (s.d. 4.5) months, mean (s.d.) sample size 32.4 (32.6) and 26.7 (27.8) in intervention and control arms, respectively. The 17 site modified Rodnan skin score is a fully validated primary outcome measure in diffuse cutaneous SSc. Skin histology seems to be an appropriate method for evaluation of skin thickness. These findings have important implications for clinical trial design targeting skin involvement in SSc. PMID- 28992174 TI - Interstitial lung disease points to consider for clinical trials in systemic sclerosis. AB - Interstitial lung disease causes major morbidity and mortality in patients with systemic sclerosis (SSc-ILD). Large randomized clinical trials in SSc-ILD have provided important information regarding the feasibility, reliability and validity of outcome measures. Forced vital capacity percentage predicted should be considered as a primary outcome measure, with inclusion of appropriate radiological and patient-reported measures. We provide practical recommendations for trial design in SSc-ILD. PMID- 28992176 TI - Disproportionate Exposure to Antibiotics in Children at Risk for Invasive Pneumococcal Disease: Potential for Emerging Resistance and Opportunity for Antibiotic Stewardship. AB - We compared antibiotic prescribing for children with and those without an underlying chronic condition associated with increased risk for invasive pneumococcal disease. Children with a chronic condition had significantly greater cumulative exposure to antibiotics and higher rates of prescriptions per person year than those without a chronic condition; this population is at increased risk for the emergence of multidrug-resistant pathogens. PMID- 28992177 TI - Cutin from agro-waste as a raw material for the production of bioplastics. AB - Cutin is the main component of plant cuticles constituting the framework that supports the rest of the cuticle components. This biopolymer is composed of esterified bi- and trifunctional fatty acids. Despite its ubiquity in terrestrial plants, it has been underutilized as raw material due to its insolubility and lack of melting point. However, in recent years, a few technologies have been developed to obtain cutin monomers from several agro-wastes at an industrial scale. This review is focused on the description of cutin properties, biodegradability, chemical composition, processability, abundance, and the state of art of the fabrication of cutin-based materials in order to evaluate whether this biopolymer can be considered a source for the production of renewable materials. PMID- 28992178 TI - Tadalafil Improves L-NG-Nitroarginine Methyl Ester-Induced Preeclampsia With Fetal Growth Restriction-Like Symptoms in Pregnant Mice. AB - BACKGROUND: We investigated the efficacy and mechanisms of tadalafil, a selective phosphodiesterase 5 inhibitor, in treating preeclampsia (PE) with fetal growth restriction (FGR) using L-NG-nitroarginine methyl ester (L-NAME)-induced PE with FGR in pregnant mice as our experimental model. METHODS: C57BL/6 mice were divided into 2 groups 11 days postcoitum (d.p.c.). A control group of dams (C dam) received 0.5% carboxymethylcellulose (CMC). A L-NAME-treated group received 1 mg/ml L-NAME dissolved in CMC. The L-NAME-treated dams were divided into 2 subgroups 13 d.p.c. One subgroup continued to receive L-NAME (L dams). The other subgroup received L-NAME with 0.08 mg/ml tadalafil suspended in CMC (TL dams). Maternal systolic blood pressure (SBP) and proteinuria were assessed 16 d.p.c. Fetal weight was recorded, and placentas and maternal kidneys were collected 17 d.p.c. RESULTS: Maternal SBP, proteinuria, and fetal weight were improved for TL dams compared to L dams. The placental concentration of placental growth factor (PlGF) was higher for TL dams than for the C and L dams. The placental maternal blood sinuses of L dams were narrower than those of C dams, but those of TL dams improved to a similar width as C dams. Glomerular oxidative stress was ameliorated in TL dams compared to L dams. CONCLUSIONS: Tadalafil dilates the placental maternal blood sinuses, which leads to increase PlGF production, and contributes to facilitate fetal growth and improve maternal SBP. Moreover, tadalafil ameliorates glomerular damage by reducing oxidative stress. These results suggest that tadalafil is a candidate for treatment of PE with FGR. PMID- 28992179 TI - Overexpression of the class D MADS-box gene Sl-AGL11 impacts fleshy tissue differentiation and structure in tomato fruits. AB - MADS-box transcription factors are key elements of the genetic networks controlling flower and fruit development. Among these, the class D clade gathers AGAMOUS-like genes which are involved in seed, ovule, and funiculus development. The tomato genome comprises two class D genes, Sl-AGL11 and Sl-MBP3, both displaying high expression levels in seeds and in central tissues of young fruits. The potential effects of Sl-AGL11 on fruit development were addressed through RNAi silencing and ectopic expression strategies. Sl-AGL11-down-regulated tomato lines failed to show obvious phenotypes except a slight reduction in seed size. In contrast, Sl-AGL11 overexpression triggered dramatic modifications of flower and fruit structure that include: the conversion of sepals into fleshy organs undergoing ethylene-dependent ripening, a placenta hypertrophy to the detriment of locular space, starch and sugar accumulation, and an extreme softening that occurs well before the onset of ripening. RNA-Seq transcriptomic profiling highlighted substantial metabolic reprogramming occurring in sepals and fruits, with major impacts on cell wall-related genes. While several Sl-AGL11 related phenotypes are reminiscent of class C MADS-box genes (TAG1 and TAGL1), the modifications observed on the placenta and cell wall and the Sl-AGL11 expression pattern suggest an action of this class D MADS-box factor on early fleshy fruit development. PMID- 28992180 TI - Integrating "Evo" and "Devo": The Limb as Model Structure. AB - Reconciling the origins of morphological diversity with the deep homology of underlying mechanisms is a question fundamental to the goals of evolutionary developmental biology ("evo-devo" or EDB). In this paper I argue that differing research agendas in evolutionary and developmental biology have hindered how we address this question, but that the limb provides ideal "common ground" for their fuller integration. To support this idea, I review two previous analyses of limb variation in mammal, bird, and reptile taxa that offer complementary approaches to explaining diversity. Specifically, I present evidence suggesting that: (1) a shared genetic architecture affects the pattern of between limb developmental integration, while their functional dissociation is linked to both increased phenotypic evolvability and diversity of interlimb proportions, and (2) within limb proportional diversity is biased such that proximal and distal segments function as tradeoffs while the middle segment is more conservative, a signal that is both evident from early in morphogenesis and suggestive of an "inhibitory cascade" model of limb proximo-distal axis development. In the first case, shared genetic mechanisms predict both observed developmental integration between limbs and patterns of clade-specific diversity. In the second case, underappreciated patterns of phenotypic diversity suggest novel insights into the underlying developmental mechanisms by which variation is generated. These studies show how insights from both evolutionary and developmental biology of the limb may be used to generate novel testable hypotheses into the origins of diversity that are broadly applicable to the integration of EDB. PMID- 28992181 TI - Requirement of glycosylation machinery in TLR responses revealed by CRISPR/Cas9 screening. AB - The Toll family of receptors sense microbial products and activate a defense response. The molecular machinery required for the TLR response is not yet fully understood. In the present study, we used a clustered, regularly interspaced, short palindromic repeats (CRISPR)/CAS9 screening system to study TLR responses. We employed a cell line expressing TLR with an NF-kappaB-driven GFP reporter. The cell line was transduced with a guide RNA (gRNA) library and stimulated with TLR ligands. The cells impaired in GFP induction were sorted, and gRNAs were sequenced. Identified genes were ranked according to the count of sequence reads and the number of gRNA target sites. The screening system worked correctly, as molecules that were already known to be required for the TLR response were identified by the screening. Furthermore, this system revealed that the oligosaccharide transferase complex (OSTC) mediating co-translational glycosylation was required for TLR5, 7 and 9 responses. Protein expression of TLR5, but not an irrelevant molecule (CD44), was abolished by the lack of OSTC, suggesting the essential role of glycosylation in TLR5 protein stability. These results demonstrate that the screening system established here is able to reveal molecular mechanisms underlying the TLR response. PMID- 28992182 TI - Association of DNA repair gene polymorphisms with genotoxic stress in underground coal miners. AB - In underground coal mining, numerous harmful substances and ionising radiation pose a major threat to the occupational safety and health of workers. Because cell DNA repair machinery eliminates genotoxic stress conferred by these agents, we examined whether single nucleotide polymorphisms in hOGG1 (rs1052133), XRCC1 (rs25487), ADPRT (rs1136410), XRCC4 (rs6869366) and LIG4 (rs1805388) genes modulate the genotoxic damage assessed by the cytokinesis-block micronucleus assay in lymphocytes from 143 underground coal miners and 127 healthy non-exposed males. We also analyzed models of gene-gene interactions associated with increased cytogenetic damage in coal miners and determined 'protective' and 'risk' combinations of alleles. We showed that miners with the G/G genotype of the hOGG1 (rs1052133) gene had a significantly increased frequency of binucleated lymphocytes with micronuclei (13.170/00, 95% CI = 10.78-15.56) compared to the C/C genotype carriers (10.350/00, 95% CI = 9.59-11.18). In addition, in the exposed group this indicator was significantly increased in carriers of the T/T genotype of the LIG4 (rs1805388) gene compared to miners harbouring the C/T genotype (13.000/00, 95% CI = 10.96-15.04 and 9.690/00, 95% CI = 8.32-11.06, respectively). Using the multifactor dimensionality reduction method, we found the three-locus model of gene-gene interactions hOGG1 (rs1052133) * ADPRT (rs1136410) * XRCC4 (rs6869366) associated with high genotoxic risk in coal miners. These results indicate that the studied polymorphisms and their combinations are associated with cytogenetic status in miners and may be used as molecular predictors of occupational risks in underground coal mines. PMID- 28992185 TI - Accuracy of Administrative Data for Antimicrobial Administration in Hospitalized Children. AB - Administrative data are often used as a proxy for medication-administration record (MAR) data. Multicenter MAR data were compared retrospectively with administrative data from January 2010 through June 2013 from the Pediatric Health Information Systems database. We found that administrative data were more concordant with bill-upon-administration than bill-upon-dispense data. PMID- 28992184 TI - Immune complexes containing serum B-cell activating factor and immunoglobulin G correlate with disease activity in systemic lupus erythematosus. AB - Methods: Levels of serum BAFF, IgG anti-BAFF and BAFF-IgG complexes were quantified by enzyme-linked immunosorbent assay. IgG anti-BAFF and BAFF-IgG complexes were further characterized using serum fractions obtained by fast protein liquid chromatography. To study the association of serum BAFF, IgG anti BAFF and BAFF-IgG complex levels with SLE manifestations, 373 visits from 178 patients prospectively included in the Swiss SLE Cohort Study were analysed. Results: While IgG anti-BAFF levels were not associated with clinical manifestations of SLE, serum BAFF levels correlated with disease activity and were higher in patients with renal involvement. Interestingly, we could also demonstrate the occurrence of BAFF-IgG complexes of different sizes in the sera of SLE patients, which were not due to treatment with belimumab and differed from complexes constructed in vitro. Most strikingly, the levels of these BAFF-IgG complexes were found to strongly correlate with overall disease activity, low complement levels and a history of lupus nephritis. Conclusion: BAFF-IgG complexes strongly correlate with disease activity in SLE patients, suggesting a pathogenic role in SLE. PMID- 28992186 TI - Evolution of nuclear auxin signaling: lessons from genetic studies with basal land plants. AB - Auxin plays critical roles in growth and development through the regulation of cell differentiation, cell expansion, and pattern formation. The auxin signal is mainly conveyed through a so-called nuclear auxin pathway involving the receptor TIR1/AFB, the transcriptional co-repressor AUX/IAA, and the transcription factor ARF with direct DNA-binding ability. Recent progress in sequence information and molecular genetics in basal plants has provided many insights into the evolutionary origin of the nuclear auxin pathway and its pleiotropic roles in land plant development. In this review, we summarize the latest knowledge of the nuclear auxin pathway gained from studies using basal plants, including charophycean green algae and two major model bryophytes, Marchantia polymorpha and Physcomitrella patens. In addition, we discuss the functional implication of the increase in genetic complexity of the nuclear auxin pathway during land plant evolution. PMID- 28992183 TI - ER stress-induced aggresome trafficking of HtrA1 protects against proteotoxicity. AB - High temperature requirement A1 (HtrA1) belongs to an ancient protein family that is linked to various human disorders. The precise role of exon 1-encoded N terminal domains and how these influence the biological functions of human HtrA1 remain elusive. In this study, we traced the evolutionary origins of these N terminal domains to a single gene fusion event in the most recent common ancestor of vertebrates. We hypothesized that human HtrA1 is implicated in unfolded protein response. In highly secretory cells of the retinal pigmented epithelia, endoplasmic reticulum (ER) stress upregulated HtrA1. HtrA1 co-localized with vimentin intermediate filaments in highly arborized fashion. Upon ER stress, HtrA1 tracked along intermediate filaments, which collapsed and bundled in an aggresome at the microtubule organizing center. Gene silencing of HtrA1 altered the schedule and amplitude of adaptive signaling and concomitantly resulted in apoptosis. Restoration of wild-type HtrA1, but not its protease inactive mutant, was necessary and sufficient to protect from apoptosis. A variant of HtrA1 that harbored exon 1 substitutions displayed reduced efficacy in rescuing cells from proteotoxicity. Our results illuminate the integration of HtrA1 in the toolkit of mammalian cells against protein misfolding and the implications of defects in HtrA1 in proteostasis. PMID- 28992188 TI - Strengthening public health capacity through a health promotion lens. PMID- 28992187 TI - Sorting of SEC translocase SCY components to different membranes in chloroplasts. AB - Membrane proteins that are imported into chloroplasts must be accurately routed in order to establish and maintain the highly differentiated membranes characteristic of these organelles. Little is known about the targeting information or pathways involved, especially in the case of proteins with multiple transmembrane domains. We have studied targeting of the SCY components of the two SEC translocases in chloroplasts. SCY1 and SCY2 share a similar, highly conserved structure with 10 transmembrane domains, but are targeted to different membranes: the thylakoids and inner envelope, respectively. We used protoplast transfections and a confocal microscopy imaging assay in combination with a domain-swapping approach to investigate sorting pathways and identify important targeting elements in these proteins. We show that the N-terminal region of SCY1 contains targeting determinants that allow SCY1 to be recruited to the signal-recognition particle pathway. In addition, substituting the N-terminal region of SCY1 for the N-terminal region of SCY2 causes SCY2 to be displaced out of the inner envelope. The region of SCY2 that contains transmembrane domains 3 and 4 is necessary for localization to the inner envelope and may serve as a membrane anchor, enhancing the integration of other transmembrane domains via either stop-transfer or post-import mechanisms. PMID- 28992189 TI - Vitamin K antagonist use and mortality in dialysis patients. AB - Background: The risk-benefit ratio of vitamin K antagonists for different CHA2DS2 VASc scores in patients with end-stage renal disease treated with dialysis is unknown. The aim of this study was to investigate the association between vitamin K antagonist use and mortality for different CHA2DS2-VASc scores in a cohort of end-stage renal disease patients receiving dialysis treatment. Methods: We prospectively followed 1718 incident dialysis patients. Hazard ratios were calculated for all-cause and cause-specific (stroke, bleeding, cardiovascular and other) mortality associated with vitamin K antagonist use. Results: Vitamin K antagonist use as compared with no vitamin K antagonist use was associated with a 1.2-fold [95% confidence interval (95% CI) 1.0-1.5] increased all-cause mortality risk, a 1.5-fold (95% CI 0.6-4.0) increased stroke mortality risk, a 1.3-fold (95% CI 0.4-4.2) increased bleeding mortality risk, a 1.2-fold (95% CI 0.9-1.8) increased cardiovascular mortality risk and a 1.2-fold (95% CI 0.8-1.6) increased other mortality risk after adjustment. Within patients with a CHA2DS2-VASc score <=1, vitamin K antagonist use was associated with a 2.8-fold (95% CI 1.0-7.8) increased all-cause mortality risk as compared with no vitamin K antagonist use, while vitamin K antagonist use within patients with a CHA2DS2-VASc score >=2 was not associated with an increased mortality risk after adjustment. Conclusion: Vitamin K antagonist use was not associated with a protective effect on mortality in the different CHA2DS2-VASc scores in dialysis patients. The lack of knowledge on the indication for vitamin K antagonist use could lead to confounding by indication. PMID- 28992191 TI - Obayashi et al. Respond to "Light at Night Predicts Depression-What Next?" PMID- 28992190 TI - Identification of novel splicing variants of protein tyrosine phosphatase receptor type Z. AB - Protein tyrosine phosphatase receptor type Z (PTPRZ, also known as PTPzeta or RPTPbeta) is preferentially expressed in the central nervous system (CNS). PTPRZ plays important roles during development and adulthood in CNS myelination, learning and memory. Three splicing isoforms for PTPRZ have been identified to date: two receptor type isoforms, PTPRZ-A and PTPRZ-B, and one secretory isoform, PTPRZ-S. We herein identified novel PTPRZ receptor sub-isoforms without a seven amino acid sequence encoded by exon 16. This sequence forms a part of the helix turn-helix segment called the 'wedge' structure, which is located at the N terminal region in the membrane-proximal protein tyrosine phosphatase domain. In contrast to conventional receptor isoforms with uniform expression, the deleted isoforms were expressed in the brain, but not in the retina, indicating the tissue-specific splicing of exon 16. Biochemical analyses of PTPRZ intracellular regions revealed differences in the characteristics of the deleted form, namely, stronger binding activity to postsynaptic density protein 95 (PSD95) and greater enrichment in the postsynaptic density fraction than the full-length form. Furthermore, the exon 16-deleted form exhibited higher catalytic efficiency in vitro. These results suggest that sub-isoforms of PTPRZ have different functions because of variations in the wedge structure. PMID- 28992192 TI - Association of Blood Pressure Variability Ratio With Glomerular Filtration Rate Independent of Blood Pressure and Pulse Wave Velocity. AB - BACKGROUND: Blood pressure variability ratio (BPVR)(derived from within-subject SD of 24-hour ambulatory blood pressure [BP]) predicts all-cause mortality independent of BP and has a similar prognostic ability to ambulatory arterial stiffness (AASI). Whether BPVR, and AASI, offer prognostic information beyond measurements of arterial stiffness at a given pressure, as indexed by pulse wave velocity (PWV), is not known. METHODS: We assessed whether BPVR and AASI were associated with indices of subclinical organ damage (TOD) [estimated glomerular filtration rate (eGFR), left ventricular mass index, early-to-late transmitral velocity (E/A), carotid intima-media thickness (IMT)] independent of BP, and whether BPVR-TOD and AASI-TOD relations were independent of PWV (applanation tonometry) in 772 randomly selected participants from an urban, developing community. AASI was derived from 24-hour diastolic BP vs. systolic BP standard linear regression. RESULTS: On bivariate analyses, BPVR, AASI, and PWV were correlated with all indices of TOD (P < 0.0005). However, after adjustments for potential confounders including age and 24-hour mean BP, BPVR, and PWV (P < 0.005 to P < 0.0001), but not AASI (P > 0.25), were independently associated with eGFR, but not other indices of TOD. Importantly, the BPVR-eGFR relation was independent of BP variability (P < 0.005) and PWV (P < 0.001). CONCLUSIONS: BPVR was negatively associated with eGFR independent of mean BP, BP variability, and PWV. Therefore, in the prediction of cardiovascular risk, measurements of arterial stiffening (BPVR) may provide information beyond the impact of arterial stiffness. PMID- 28992193 TI - Pulse Pressure Within 3 Months After Ischemic Stroke Is Associated With Long-Term Stroke Outcomes. AB - BACKGROUND: Pulse pressure (PP) is a surrogate marker of arterial stiffness. Studies on baseline PP and long-term outcomes in patients with stroke are limited. We aimed to evaluate whether PP within 3 months after ischemic stroke was associated with long-term stroke outcomes. METHODS: A total of 4,195 patients (61.2 +/- 11.6 years, 68.4% men) with first-ever ischemic stroke in 3 months had baseline blood pressure (BP) measured. Study end-points were the combined end points (recurrent vascular events and all-cause mortality) and recurrent stroke. RESULTS: In the group <60 years of age, the BP components of systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), or PP did not significantly correlate with long-term stroke outcomes. In the group >=60 years of age, PP was significantly associated with combined end-points (hazards ratio [HR] = 1.35; 95% confidence interval [CI], 1.18-1.54) and recurrent stroke (HR = 1.46; 95% CI, 1.24-1.72). Combination of SBP and PP, DBP and PP, or MAP and PP, respectively, showed no incremental value of SBP, DBP, or MAP in predicting long-term stroke outcomes. CONCLUSIONS: PP was significantly associated with long-term stroke outcomes, and this association was prominent in patients with stroke older than 60 years of age. PMID- 28992194 TI - A Novel Display System Reveals Anisotropic Polarization Perception in the Motion Vision of the Butterfly Papilio xuthus. AB - While the linear polarization of light is virtually invisible to humans, many invertebrates' eyes can detect it. How this information is processed in the nervous system, and what behavioral function it serves, are in many cases unclear. One reason for this is the technical difficulty involved in presenting images or video containing polarization contrast, particularly if intensity and/or color contrast is also required. In this primarily methods-focused article, we present a novel technique based on projecting video through a synchronously rotating linear polarizer. This approach allows the intensity, angle of polarization, degree of linear polarization, and potentially also color of individual pixels to be controlled independently. We characterize the performance of our system, and then use it to investigate the relationship between polarization and motion vision in the swallowtail butterfly Papilio xuthus. Although this animal has photoreceptors sensitive to four different polarization angles, we find that its motion vision cannot distinguish between diagonally-polarized and unpolarized light. Furthermore, it responds more strongly to vertically-polarized moving objects than horizontally-polarized ones. This implies that Papilio's polarization-based motion detection employs either an unbalanced two-channel (dipolatic) opponent architecture, or possibly a single channel (monopolatic) scheme without opponent mechanisms. PMID- 28992195 TI - Neural Versus Gonadal GnIH: Are they Independent Systems? A Mini-Review. AB - Based on research in protochordates and basal vertebrates, we know that communication across the first endocrine axes likely relied on diffusion. Because diffusion is relatively slow, rapid responses to some cues, including stress related cues, may have required further local control of axis outputs (e.g., steroid hormone production by the gonads). Despite the evolution of much more efficient circulatory systems and complex nervous systems in vertebrates, production of many "neuro"transmitters has been identified outside of the hypothalamus across the vertebrate phylogeny and these neurotransmitters are known to locally regulate endocrine function. Our understanding of tissue specific neuropeptide expression and their role coordinating physiological/behavioral responses of the whole organism remains limited, in part, due to nomenclature and historic dogma that ignores local regulation of axis output. Here, we review regulation of gonadotropin-inhibitory hormone (GnIH) across the reproductive axis in birds and mammals to bring further attention to context-dependent disparities and similarities in neuropeptide production by the brain and gonads. We find that GnIH responsiveness to cues of stress appears conserved across species, but that the response of specific tissues and the direction of GnIH regulation varies. The implications of differential regulation across tissues remain unclear in most studies, but further work that manipulates and contrasts function in different tissues has the potential to inform us about both organism-specific function and endocrine axis evolution. PMID- 28992196 TI - Canalization of Seasonal Phenology in the Presence of Developmental Variation: Seed Dormancy Cycling in an Annual Weed. AB - Variation in the developmental timing in one life stage may ramify within and across generations to disrupt optimal phenology of other life stages. By focusing on a common mechanism of developmental arrest in plants-seed dormancy-we investigated how variation in flowering time influenced seed germination behavior and identified potential processes that can lead to canalized germination behavior despite variation in reproductive timing. We quantified effects of reproductive timing on dormancy cycling by experimentally manipulating the temperature during seed maturation and the seasonal timing of seed dispersal/burial, and by assessing temperature-dependent germination of un earthed seeds over a seasonal cycle. We found that reproductive timing, via both seed-maturation temperature and the timing of dispersal, strongly influenced germination behavior in the weeks immediately following seed burial. However, buried seeds subsequently canalized their germination behavior, after losing primary dormancy and experiencing natural temperature and moisture conditions in the field. After the complete loss of primary dormancy, germination behavior was similar across seed-maturation and dispersal treatments, even when secondary dormancy was induced. Maternal effects themselves may contribute to the canalization of germination: first, by inducing stronger dormancy in autumn matured seeds, and second by modifying the responses of those seeds to their ambient environment. Genotypes differed in dormancy cycling, with functional alleles of known dormancy genes necessary for the suppression of germination at warm temperatures in autumn through spring across multiple years. Loss of function of dormancy genes abolished almost all dormancy cycling. In summary, effects of reproductive phenology on dormancy cycling of buried seeds were apparent only as long as seeds retained primary dormancy, and a combination of genetically imposed seed dormancy, maternally induced seed dormancy, and secondary dormancy can mitigate variation in germination behavior imposed by variation in reproductive phenology. PMID- 28992198 TI - Analysing the dynamics of a model for alopecia areata as an autoimmune disorder of hair follicle cycling. AB - Alopecia areata (AA) is a CD8$^{+}$ T cell-dependent autoimmune disease that disrupts the constantly repeating cyclic transformations of hair follicles (HFs). Among the three main HF cycle stages-growth (anagen), regression (catagen) and relative quiescence (telogen)-only anagen HFs are attacked and thereby forced to prematurely enter into catagen, thus shortening active hair growth substantially. After having previously modelled the dynamics of immune system components critically involved in the disease development (Dobreva et al., 2015), we here present a mathematical model for AA which incorporates HF cycling and illustrates the anagen phase interruption in AA resulting from an inflammatory autoimmune response against HFs. The model couples a system describing the dynamics of autoreactive immune cells with equations modelling the hair cycle. We illustrate states of health, disease and treatment as well as transitions between them. In addition, we perform parameter sensitivity analysis to assess how different processes, such as proliferation, apoptosis and input from stem cells, impact anagen duration in healthy versus AA-affected HFs. The proposed model may help in evaluating the effectiveness of existing treatments and identifying new potential therapeutic targets. PMID- 28992199 TI - Retention of Core Meiotic Genes Across Diverse Hymenoptera. AB - The cellular mechanisms of meiosis are critical for proper gamete formation in sexual organisms. Functional studies in model organisms have identified genes essential for meiosis, yet the extent to which this core meiotic machinery is conserved across non-model systems is not fully understood. Moreover, it is unclear whether deviation from canonical modes of sexual reproduction is accompanied by modifications in the genetic components involved in meiosis. We used a robust approach to identify and catalogue meiosis genes in Hymenoptera, an insect order typically characterized by haplodiploid reproduction. Using newly available genome data, we searched for 43 genes involved in meiosis in 18 diverse hymenopterans. Seven of eight genes with roles specific to meiosis were found across a majority of surveyed species, suggesting the preservation of core meiotic machinery in haplodiploid hymenopterans. Phylogenomic analyses of the inventory of meiosis genes and the identification of shared gene duplications and losses provided support for the grouping of species within Proctotrupomorpha, Ichneumonomorpha, and Aculeata clades, along with a paraphyletic Symphyta. The conservation of meiosis genes across Hymenoptera provides a framework for studying transitions between reproductive modes in this insect group. PMID- 28992200 TI - Effects of Radiation From Contaminated Soil and Moss in Fukushima on Embryogenesis and Egg Hatching of the Aphid Prociphilus oriens. AB - Radiation-contaminated soils are widespread around the Fukushima Daiichi Nuclear Power Plant, and such soils raise concerns over its harmful effect on soil dwelling organisms. We evaluated the effects of contaminated soil and moss sampled in Fukushima on the embryogenesis and hatching of aphid eggs, along with the measurement of the egg exposure dose. Cs-137 concentration in soil and moss from Fukushima ranged from 2200 to 3300 Bq/g and from 64 to 105 Bq/g, respectively. Eggs of the eriosomatine aphid Prociphilus oriens that were collected from a non-contaminated area were directly placed on the soil and moss for 4 or 3 months during diapause and then incubated until hatching. The total exposure dose to the eggs was estimated as ca. 100-200 mGy in the 4-month soil experiment and 4-10 mGy in the 4-month moss experiment. There was no significant difference in egg hatchability between the contaminated soil treatment and the control. No morphological abnormalities were detected in the first instars that hatched from the contaminated soil treatment. However, we found weak effects of radiation on egg hatching; eggs placed on the contaminated moss hatched earlier than did the control eggs. On the contaminated soil, the effects of radiation on egg hatching were not obvious because of uncontrolled environmental differences among containers. The effects of radiation on egg hatching were detected only in containers where high hatchability was recorded. Through the experiments, we concluded that the aphid eggs responded to ultra-low-dose radiation by advancing embryogenesis. PMID- 28992197 TI - Relating cell shape and mechanical stress in a spatially disordered epithelium using a vertex-based model. AB - Using a popular vertex-based model to describe a spatially disordered planar epithelial monolayer, we examine the relationship between cell shape and mechanical stress at the cell and tissue level. Deriving expressions for stress tensors starting from an energetic formulation of the model, we show that the principal axes of stress for an individual cell align with the principal axes of shape, and we determine the bulk effective tissue pressure when the monolayer is isotropic at the tissue level. Using simulations for a monolayer that is not under peripheral stress, we fit parameters of the model to experimental data for Xenopus embryonic tissue. The model predicts that mechanical interactions can generate mesoscopic patterns within the monolayer that exhibit long-range correlations in cell shape. The model also suggests that the orientation of mechanical and geometric cues for processes such as cell division are likely to be strongly correlated in real epithelia. Some limitations of the model in capturing geometric features of Xenopus epithelial cells are highlighted. PMID- 28992201 TI - Progress Toward Rice Seed OMICS in Low-Level Gamma Radiation Environment in Iitate Village, Fukushima. AB - Here, we present an update on the next level of experiments studying the impact of the gamma radiation environment, created post-March, 2011 nuclear accident at Fukushima Daiichi nuclear power plant, on rice plant and its next generation-the seed. Japonica-type rice (Oryza sativa L. cv. Koshihikari) plant was exposed to low-level gamma radiation (~4 MUSv/h) in the contaminated Iitate Farm field in Iitate village (Fukushima). Seeds were harvested from these plants at maturity, and serve as the treated group. For control group, seeds (cv. Koshihikari) were harvested from rice grown in clean soil in Soma city, adjacent to Iitate village, in Fukushima. Focusing on the multi-omics approach, we have investigated the dry mature rice seed transcriptome, proteome, and metabolome following cultivation of rice in the radionuclide contaminated soil and compared it with the control group seed (non-radioactive field-soil environment). This update article presents an overview of both the multi-omics approach/technologies and the first findings on how rice seed has changed or adapted its biology to the low-level radioactive environment. PMID- 28992203 TI - Music Therapy Practice Status and Trends Worldwide: An International Survey Study. AB - Background: The field of music therapy is growing worldwide. While there is a wealth of country-specific information available, only a few have databased workforce censuses. Currently, little to no descriptive data exists about the global development of the profession. Objectives: The purpose of this study was to obtain descriptive data about current demographics, practice status, and clinical trends to inform worldwide advocacy efforts, training needs, and the sustainable development of the field. Method: Music therapists (N = 2,495) who were professional members of organizations affiliated with the World Federation of Music Therapy (WFMT) served as a sample for this international cross-sectional survey study. A 30-item online questionnaire was designed, pilot tested by key partners, and translated into seven languages. Researchers and key partners distributed the online survey through e-mail invitations and social media announcements. Results: Professional music therapists worldwide are well educated, mature professionals with adequate work experience, who are confident in providing high-quality services primarily in mental health, school, and geriatric settings. Due to ongoing challenges related to recognition and government regulation of the field as an evidence-based and well-funded healthcare profession, most individuals work part-time music therapy jobs and feel underpaid. Yet, many music therapists have a positive outlook on the field's future. Conclusions: Continued research and advocacy efforts, as well as collaborations with lobbyists, business consultants, and credentialing/licensure experts to develop progressive strategies, will be crucial for global development and sustainability of the field. PMID- 28992204 TI - Quality Improvement Feature Series Article 1: Introduction to Quality Improvement. AB - Quality improvement methods offer a rigorous approach to designing and disseminating improvement efforts. This report is the first in a series to introduce QI methodology, effective data display, and considerations in the review of QI manuscripts. PMID- 28992205 TI - National Estimates of Reductions in Acute Gastroenteritis-Related Hospitalizations and Associated Costs in US Children After Implementation of Rotavirus Vaccines. AB - We compared acute gastroenteritis (AGE)-related hospitalization rates among children <5 years of age during the pre-rotavirus vaccine (2000-2006) and post rotavirus vaccine (2008-2013) periods to estimate national reductions in AGE related hospitalizations and associated costs. We estimate that between 2008 and 2013, AGE-related hospitalizations declined by 382000, and $1.228 billion in medical costs were averted. PMID- 28992202 TI - Kruppel-like factors and vascular wall homeostasis. AB - Cardiovascular diseases (CVDs) are major causes of death worldwide. Identification of promising targets for prevention and treatment of CVDs is paramount in the cardiovascular field. Numerous transcription factors regulate cellular function through modulation of specific genes and thereby are involved in the physiological and pathophysiological processes of CVDs. Although Kruppel like factors (KLFs) have a similar protein structure with a conserved zinc finger domain, they possess distinct tissue and cell distribution patterns as well as biological functions. In the vascular system, KLF activities are regulated at both transcriptional and posttranscriptional levels. Growing in vitro, in vivo, and genetic epidemiology studies suggest that specific KLFs play important roles in vascular wall biology, which further affect vascular diseases. KLFs regulate various functional aspects such as cell growth, differentiation, activation, and development through controlling a whole cluster of functionally related genes and modulating various signaling pathways in response to pathological conditions. Therapeutic targeting of selective KLF family members may be desirable to achieve distinct treatment effects in the context of various vascular diseases. Further elucidation of the association of KLFs with human CVDs, their underlying molecular mechanisms, and precise protein structure studies will be essential to define KLFs as promising targets for therapeutic interventions in CVDs. PMID- 28992206 TI - Dose escalation via brachytherapy boost for nasopharyngeal carcinoma in the era of intensity-modulated radiation therapy and combined chemotherapy. AB - To investigate if dose escalation using intracavitary brachytherapy (ICBT) improves local control for nasopharyngeal carcinoma (NPC) in the era of intensity modulated radiation therapy (IMRT) and concurrent chemoradiation treatment (CCRT). We retrospectively analyzed 232 patients with Stage T1-3 N0-3 M0 NPC who underwent definitive IMRT with or without additional ICBT boost between 2002 and 2013. For most of the 124 patients who had ICBT boost, the additional brachytherapy was given as 6 Gy in 2 fractions completed within 1 week after IMRT of 70 Gy. CCRT with or without adjuvant chemotherapy was used for 176 patients, including 88 with and 88 without ICBT boost, respectively. The mean follow-up time was 63.1 months. The 5-year overall survival and local control rates were 81.5% and 91.5%, respectively. ICBT was not associated with local control prediction (P = 0.228). However, in a subgroup analysis, 75 T1 patients with ICBT boost had significantly better local control than the other 71 T1 patients without ICBT boost (98.1% vs 85.9%, P = 0.020), despite having fewer patients who had undergone chemotherapy (60.0% vs 76.1%, P = 0.038). Multivariate analysis showed that both ICBT (P = 0.029) and chemotherapy (P = 0.047) influenced local control for T1 patients. Our study demonstrated that dose escalation with ICBT can improve local control of the primary tumor for NPC patients with T1 disease treated with IMRT, even without chemotherapy. PMID- 28992207 TI - Propensity Score-Based Methods in Comparative Effectiveness Research on Coronary Artery Disease. AB - This review examines the conduct and reporting of observational studies using propensity score-based methods to compare coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), or medical therapy for patients with coronary artery disease. A systematic selection process identified 48 studies: 20 addressing CABG versus PCI; 21 addressing bare-metal stents versus drug-eluting stents; 5 addressing CABG versus medical therapy; 1 addressing PCI versus medical therapy; and 1 addressing drug-eluting stents versus balloon angioplasty. Of 32 studies reporting information on variable selection, 7 relied exclusively on statistical criteria for the association of covariates with treatment, and 5 used such criteria to determine whether product or nonlinear terms should be included in the propensity score model. Twenty-five (52%) studies reported assessing covariate balance using the estimated propensity score, but only 1 described modifications to the propensity score model based on this assessment. The over 400 variables used in the 48 propensity score models were classified into 12 categories and 60 subcategories; only 17 subcategories were represented in at least half of the propensity score models. Overall, reporting of propensity score based methods in observational studies comparing CABG, PCI, and medical therapy was incomplete; when adequately described, the methods used were often inconsistent with current methodological standards. PMID- 28992208 TI - Recent advances in auxin research in rice and their implications for crop improvement. AB - Auxin is essential for various aspects of plant development, and modulation of auxin pathways has great potential for crop improvement. Although the current understanding of auxin biology including auxin biosynthesis, transport, and signaling mainly originated from studies in Arabidopsis, several key auxin genes were first discovered in rice, indicating that it is useful to employ several plant systems for auxin research. In this review, we summarize the recent advances in auxin biology in rice, highlight the main contributions of rice research to auxin biology, and discuss the potential for crop improvement through modulating auxin pathways. PMID- 28992209 TI - Protein secretion in plants: conventional and unconventional pathways and new techniques. AB - Protein secretion is an essential process in all eukaryotic cells and its mechanisms have been extensively studied. Proteins with an N-terminal leading sequence or transmembrane domain are delivered through the conventional protein secretion (CPS) pathway from the endoplasmic reticulum (ER) to the Golgi apparatus. This feature is conserved in yeast, animals, and plants. In contrast, the transport of leaderless secretory proteins (LSPs) from the cytosol to the cell exterior is accomplished via the unconventional protein secretion (UPS) pathway. So far, the CPS pathway has been well characterized in plants, with several recent studies providing new information about the regulatory mechanisms involved. On the other hand, studies on UPS pathways in plants remain descriptive, although a connection between UPS and the plant defense response is becoming more and more apparent. In this review, we present an update on CPS and UPS. With the emergence of new techniques, a more comprehensive understanding of protein secretion in plants can be expected in the future. PMID- 28992211 TI - Using Sensitivity Analyses for Unobserved Confounding to Address Covariate Measurement Error in Propensity Score Methods. AB - Propensity score methods are a popular tool with which to control for confounding in observational data, but their bias-reduction properties-as well as internal validity, generally-are threatened by covariate measurement error. There are few easy-to-implement methods of correcting for such bias. In this paper, we describe and demonstrate how existing sensitivity analyses for unobserved confounding propensity score calibration, VanderWeele and Arah's bias formulas, and Rosenbaum's sensitivity analysis-can be adapted to address this problem. In a simulation study, we examine the extent to which these sensitivity analyses can correct for several measurement error structures: classical, systematic differential, and heteroscedastic covariate measurement error. We then apply these approaches to address covariate measurement error in estimating the association between depression and weight gain in a cohort of adults in Baltimore, Maryland. We recommend the use of VanderWeele and Arah's bias formulas and propensity score calibration (assuming it is adapted appropriately for the measurement error structure), as both approaches perform well for a variety of propensity score estimators and measurement error structures. PMID- 28992212 TI - The biochemistry and molecular biology of chlorophyll breakdown. AB - Chlorophyll breakdown is one of the most obvious signs of leaf senescence and fruit ripening. The resulting yellowing of leaves can be observed every autumn, and the color change of fruits indicates their ripening state. During these processes, chlorophyll is broken down in a multistep pathway, now termed the 'PAO/phyllobilin' pathway, acknowledging the core enzymatic breakdown step catalysed by pheophorbide a oxygenase, which determines the basic linear tetrapyrrole structure of the products of breakdown that are now called 'phyllobilins'. This review provides an update on the PAO/phyllobilin pathway, and focuses on recent biochemical and molecular progress in understanding phyllobilin-modifying reactions as the basis for phyllobilin diversity, on the evolutionary diversity of the pathway, and on the transcriptional regulation of the pathway genes. PMID- 28992210 TI - The plasma membrane H+-ATPase gene family in Solanum tuberosum L. Role of PHA1 in tuberization. AB - This study presents the characterization of the plasma membrane (PM) H+-ATPases in potato, focusing on their role in stolon and tuber development. Seven PM H+ ATPase genes were identified in the Solanum tuberosum genome, designated PHA1 PHA7. PHA genes show distinct expression patterns in different plant tissues and under different stress treatments. Application of PM H+-ATPase inhibitors arrests stolon growth, promotes tuber induction, and reduces tuber size, indicating that PM H+-ATPases are involved in tuberization, acting at different stages of the process. Transgenic potato plants overexpressing PHA1 were generated (PHA1-OE). At early developmental stages, PHA1-OE stolons elongate faster and show longer epidermal cells than wild-type stolons; this accelerated growth is accompanied by higher cell wall invertase activity, lower starch content, and higher expression of the sucrose-H+ symporter gene StSUT1. PHA1-OE stolons display an increased branching phenotype and develop larger tubers. PHA1-OE plants are taller and also present a highly branched phenotype. These results reveal a prominent role for PHA1 in plant growth and development. Regarding tuberization, PHA1 promotes stolon elongation at early stages, and tuber growth later on. PHA1 is involved in the sucrose-starch metabolism in stolons, possibly providing the driving force for sugar transporters to maintain the apoplastic sucrose transport during elongation. PMID- 28992213 TI - Repression of TERMINAL FLOWER1 primarily mediates floral induction in pear (Pyrus pyrifolia Nakai) concomitant with change in gene expression of plant hormone related genes and transcription factors. AB - Floral induction is an important event in the annual growth cycle of perennial fruit trees. For pear, this event directly affects fruit production in the following year. The flower buds in many species are induced by FLOWERING LOCUS T (FT), whose effect is repressed by the meristem-expressed gene TERMINAL FLOWER1 (TFL1). In this study, we investigated the functions of pear FT and TFL1 genes during floral development. Expression of pear FTs (PpFT1a and PpFT2a) in reproductive meristems was not obviously induced prior to floral initiation, while expression of TFL1s (PpTFL1-1a and PpTFL1-2a) rapidly decreased. The induction of the productive meristem identity MADS-box gene AP1 after repression of PpTFL1s suggested a primary role for PpTFL1 in floral induction. RNA-seq analysis suggested that plant hormone-related genes and several transcription factors that were coexpressed with PpTFL1 were potentially involved in the PpTFL1 mediated floral induction. Our data indicate the essential function of TFL1 in pear floral induction and add another species in the family Rosaceae in addition to strawberry and rose that shows a role for TFL1 in floral induction. PMID- 28992214 TI - Differential production of interleukin-1 family cytokines (IL-1beta, IL-18, IL-33 and IL-37) in patients with paracoccidioidomycosis: correlation with clinical form and antifungal therapy. AB - Besides interleukin (IL)-1beta and IL-18, the newly described cytokines of IL-1 family IL-33 and IL-37 can contribute to the differentiation and maintenance of different population of T cells. IL-33 acts as an allarmin and promotes a predominant Th2 inflammatory response, whereas IL-37 plays an important role as an antagonist of inflammation. In paracoccidioidomycosis (PCM), caused by the dimorphic fungi Paracoccidioides brasiliensis and P. lutzii, it has been shown that the acquired immune responses are associated with the diverse clinical manifestations. The severe and disseminated forms (acute form [AF] and multifocal chronic form [CF-MF]) are characterized by high Th2 cytokines and antibody production, impaired cellular immune response, and eosinophilia. In contrast, in the localized form (unifocal chronic form [CF-UF]), the cellular immune response is preserved, with high production of Th1 and Th17 cytokines, and low antibody titers. This study aimed to quantify interleukin-1 family cytokines (IL-1beta, IL 18, IL-37, IL-33, and the soluble IL-33 receptor sST2) in sera of patients presenting different clinical forms of PCM before, during, and after antifungal treatment, as well as to analyze the expression of these cytokines in lesions of PCM patients. We found that AF patients presented high serum levels of IL-1beta, IL-18, IL-33, sST2, and IL-37, and that these cytokines are strongly expressed in lymph nodes lesions. Furthermore, antifungal therapy resulted in the diminution of circulating cytokines and sST2 levels in all groups of patients. These results indicate that, besides IL-1beta and IL-18, IL-33, IL-37, and sST2 can be associated with the disease activity and severity. PMID- 28992215 TI - Thermal Performance Curves Reveal Variation in the Seasonal Niche of a Short Lived Annual. AB - An organism's environment can vary over spatial and temporal scales. Seasonal variation is an important but overlooked source of environmental variation that often shapes the ranges of organisms. The seasonal niche is a description of the spatiotemporal range of an organism resulting from spatial variation in seasonal conditions. In this study, I describe the seasonal niche of a short-lived annual plant, and variation within the species in seasonal niche breadth. I construct a seasonal species distribution model (SDM) for the species, and using thermal performance curves (TPCs), construct mechanistic SDMs (MSDMs) for individual genotypes. I quantify the correlation between the suitability scores generated in the SDM and the predicted dry weight generated by the MSDMs for each genotype, to estimate variation in seasonal niche breadth among genotypes. Thus, the parameters of TPCs reflect generalist/specialist strategies. I detected significant relationships between thermal performance breadth and maximum predicted fitness and significant correlations between optimal growth temperature and thermal performance breadth. There were large positive correlations between predictions of the SDM and MSDMs based on growth within individual genotypes. The variation in these correlations suggests variation in the degree of specialization. Genotypes with the broadest TPCs had the largest correlations between their MSDMs and the SDM, suggesting that they were generalists. The results show that correlative and MSDMs make similar predictions over the seasonal range, and that ecological specialization can vary dramatically within species. PMID- 28992216 TI - Links between Natural Variation in the Microbiome and Host Fitness in Wild Mammals. AB - Recent studies in model organisms have shown that compositional variation in the microbiome can affect a variety of host phenotypes including those related to digestion, development, immunity, and behavior. Natural variation in the microbiome within and between natural populations and species may also affect host phenotypes and thus fitness in the wild. Here, I review recent evidence that compositional variation in the microbiome may affect host phenotypes and fitness in wild mammals. Studies over the last decade indicate that natural variation in the mammalian microbiome may be important in the assistance of energy uptake from different diet types, detoxification of plant secondary compounds, protection from pathogens, chemical communication, and behavior. I discuss the importance of combining both field observations and manipulative experiments in a single system to fully characterize the functions and fitness effects of the microbiome. Finally, I discuss the evolutionary consequences of mammal-microbiome associations by proposing a framework to test how natural selection on hosts is mediated by the microbiome. PMID- 28992217 TI - Closing the mycetoma knowledge gap. AB - On 28th May 2016, mycetoma was recognized as a neglected tropical disease by the World Health Organization. This was the result of a 4-year journey starting in February 2013 with a meeting of global mycetoma experts. Knowledge gaps were identified and included the incidence, prevalence, and mapping of mycetoma; the mode of transmission; the development of methods for early diagnosis; and better treatment. In this review, we review the road to recognition, the ISHAM working group meeting in Argentina, and we address the progress made in closing the knowledge gaps since 2013. Progress included adding another 9000 patients to the literature, which allowed us to update the prevalence map on mycetoma. Furthermore, based on molecular phylogeny, species names were corrected and four novel mycetoma causative agents were identified. By mapping mycetoma causative agents an association with Acacia trees was found. For early diagnosis, three different isothermal amplification techniques were developed, and novel antigens were discovered. To develop better treatment strategies for mycetoma patients, in vitro susceptibility tests for the coelomycete agents of black grain mycetoma were developed, and the first randomized clinical trial for eumycetoma started early 2017. PMID- 28992218 TI - Long-term consequences of renal insufficiency in children: lessons learned from the Dutch LERIC study. AB - Few data exist on the prospects in adulthood for children on chronic renal replacement therapy (RRT). This article summarizes the results of a comprehensive Dutch long-term follow-up study performed in 2000 and 2010 of patients with RRT onset at age <15 years between 1972 and 1992. After a median of 25.5 RRT years, patients had stayed 23% of RRT time on dialysis. We observed a 30 times greater mortality risk compared with age-matched peers with cardiovascular disease (CVD) as the main cause of death during 1972-2000 and infections during 2000-10. The observed shift towards infections was associated with more RRT time with a graft and receiving a stricter CVD protective treatment. For patients >40 years of age, motor disabilities affecting routine activities, skin cancer and severe fatigue were the most disabling sequelae. After 30 years of transplantation, 41% of the survivors had developed cancer, a life-threatening form of squamous cell skin carcinoma being most prevalent. Important delays in autonomy development and educational attainment and a relatively high level of unemployment were observed. Transplanted patients reported a good mental and physical quality of life, but the latter tended to decrease over time. A long period of dialysis was associated with all adverse somatic and psychosocial outcomes. Paediatric nephrologists should aim for transplantation at the earliest possible time and focus on autonomy and educational attainment. Nephrologists should focus on strict CVD prevention, adjustment of immunosuppression to the lowest possible dose and surveillance of malignancy-associated viral infections in patients with childhood end-stage renal disease. PMID- 28992219 TI - Childhood Health Outcomes in Term, Large-for-Gestational-Age Babies With Different Postnatal Growth Patterns. AB - Large-for-gestational-age (LGA) babies have a higher risk of metabolic disease later in life, and their postnatal growth in early childhood may be associated with long-term adverse outcomes. This study aimed to determine childhood health outcomes of term LGA babies with different growth patterns. Data were obtained from the US Collaborative Perinatal Project for the years between 1959 and 1976. The growth trajectories of 3,316 term LGA babies were identified and odds ratios of obesity, growth restriction, low intelligence quotient (IQ), and high blood pressure (HBP) were calculated by logistic regression. Compared with term appropriate-for-gestational-age infants, term LGA babies without catch-down growth had increased risks of obesity (adjusted odds ratio (aOR) = 6.37, 95% confidence interval (CI): 5.24, 7.73) and HBP (aOR = 1.67, 95% CI: 1.37, 2.03). Those with high catch-down growth had higher risks of growth restriction (aOR = 2.21, 95% CI: 1.66, 2.95) and low IQ (aOR = 1.61, 95% CI: 1.04, 2.49). Nevertheless, infants with small catch-down growth had lower risks of obesity (aOR = 0.78, 95% CI: 0.63, 0.95), growth restriction (aOR = 0.28, 95% CI: 0.17, 0.46), low IQ (aOR = 0.66, 95% CI: 0.41, 1.06), and HBP (aOR = 0.89, 95% CI: 0.77, 1.04). According to our data, term LGA infants with small catch-down growth had no increased risks of adverse outcomes. PMID- 28992221 TI - The diabetes pandemic suggests unmet needs for 'CKD with diabetes' in addition to 'diabetic nephropathy'-implications for pre-clinical research and drug testing. AB - Curing 'diabetic nephropathy' is considered an unmet medical need of high priority. We propose to question the concept of 'diabetic nephropathy' that implies diabetes as the predominant cause of kidney disease, which may not apply to the majority of type 2 diabetics approaching end-stage kidney disease. With the onset of diabetes, hyperglycaemia/sodium-glucose co-transporter-2-driven glomerular hyperfiltration promotes nephron hypertrophy, which, however, on its own, causes proteinuria not before a decade later, probably because podocyte hypertrophy can usually accommodate an increase in the filtration surface. In contrast, precedent chronic kidney disease (CKD), that is, few nephrons per body mass, e.g. due to poor nephron endowment from birth, obesity, pregnancy, or renal ageing or injury-related nephron loss, usually precedes the onset of type 2 diabetes. This applies in particular in older adults, and each on its own, but especially in combination, further aggravates single nephron hyperfiltration and glomerular hypertrophy. Whenever this additional hyperglycaemia-driven enlargement of the glomerular filtration surface exceeds the capacity of podocytes for hypertrophy, podocytes detachment leads to glomerulosclerosis and nephron loss, i.e. CKD progression. Animal models of 'diabetic nephropathy' based only on hyperglycaemia do not mimic this aspect and therefore poorly predict outcomes of clinical trials usually performed on elderly CKD patients with type 2 diabetes. Thus, we advocate the use of renal mass (nephron) ablation in type 2 diabetic animals to better mimic the pathophysiology of 'CKD with diabetes' in the target patient population and the use of the glomerular filtration rate as a primary endpoint to more reliably predict trial outcomes. PMID- 28992220 TI - Blood Pressure and Arterial Stiffness in Kenyan Adolescents With the Sickle Cell Trait. AB - The potential association between sickle cell trait (SCT) and increased arterial stiffness/blood pressure (BP) has not been evaluated in detail despite its association with stroke, sudden death, and renal disease. We performed 24-hour ambulatory BP monitoring and arterial stiffness measurements in adolescents raised in a malaria-free environment in Kenya. Between December 2015 and June 2016, 938 randomly selected adolescents (ages 11-17 years) who had been continuous residents of Nairobi from birth were invited to participate in the study. Standard clinic BP measurement was performed, followed by 24-hour ambulatory BP monitoring and arterial stiffness measurement using an Arteriograph24 (TensioMed Ltd., Budapest, Hungary) device. SCT status was determined using DNA genotyping in contemporaneously collected blood samples. Of the 938 adolescents invited to participate, 609 (65%) provided complete data for analysis. SCT was present in 103 (15%). Mean 24-hour systolic and diastolic BPs were 116 (standard deviation (SD), 11.5) mm Hg and 64 (SD, 7) mm Hg, respectively, in children with SCT and 117 (SD, 11.4) mm Hg and 64 (SD, 6.8) mm Hg, respectively, in non-SCT children. Mean pulse wave velocity (PWV) was 7.1 (SD, 0.8) m/second and 7.0 (SD, 0.8) m/second in SCT and non-SCT children, respectively. We observed no differences in PWV or in any clinic or ambulatory BP derived measures between adolescents with and without SCT. These data suggest that SCT does not independently influence BP or PWV. PMID- 28992222 TI - Affinity labelling in situ of the bL12 protein on E. coli 70S ribosomes by means of a tRNA dialdehyde derivative. AB - In this report, we have used periodate-oxidized tRNA (tRNAox) as an affinity laleling reagent to demonstrate that: (i) the bL12 protein contacts the CCA-arm of P-site bound tRNA on the Escherichia coli 70S ribosomes; (ii) the stoichiometry of labelling is one molecule of tRNAox bound to one polypeptide chain of endogenous bL12; (iii) cross-linking in situ of bL12 with tRNAox on the ribosomes provokes the loss of activity; (iv) intact tRNA protects bL12 in the 70S ribosomes against cross-linking with tRNAox; (v) both tRNAox and pyridoxal 5' phosphate (PLP) compete for the same or for proximal cross-linking site(s) on bL12 inside the ribosome; (vi) the stoichiometry of cross-linking of PLP to the recombinant E. coli bL12 protein is one molecule of PLP covalently bound per polypeptide chain; (vii) the amino acid residue of recombinant bL12 cross-linked with PLP is Lys-65; (viii) Lys-65 of E. coli bL12 corresponds to Lys-53 of eL42 which was previously shown to cross-link with P-site bound tRNAox on human 80S ribosomes in situ; (ix) finally, E. coli bL12 and human eL42 proteins display significant primary structure similarities, which argues for evolutionary conservation of these two proteins located at the tRNA-CCA binding site on eubacterial and eukaryal ribosomes. PMID- 28992223 TI - Etiology and renal outcomes of acute tubulointerstitial nephritis: a single center prospective cohort study in China. AB - Background: The aim of this study was to explore the etiology, long-term renal outcomes and affecting factors of acute tubulointerstitial nephritis (ATIN). Methods: Patients with biopsy-proven ATIN from 1 January 2005 to 31 December 2013 at Peking University First Hospital were enrolled in the study and received scheduled follow-up for at least 24 months. The causes of ATIN were defined at biopsy and reclassified during follow-up. Factors affecting renal recovery at 6 months post-biopsy and estimated glomerular filtration rate (eGFR) at 12 months post-biopsy and at the end of follow-up were analyzed. Results: A total of 157 ATIN patients were enrolled, with an average follow-up of 48 months (range 24-108 months). A modified etiology spectrum was identified, with a decreased proportion of drug-induced ATIN (D-ATIN, 64% at biopsy to 50% after follow-up) and an increase in autoimmune-related ATIN (22-41%) with late-onset systemic manifestations in patients who had been classified as D-ATIN or ATIN of unknown cause. Recurrent kidney injury was observed in 51% of the patients with tubulointerstitial nephritis and uveitis syndrome (TINU), 53% of those with an autoimmune disease and 8% of those with D-ATIN, resulting in prolonged immunosuppressive treatment. By 12 months, decreased eGFR (<60 mL/min/1.73 m2) was observed in 47% of the patients with D-ATIN, 74% of those with TINU and 57% of those with other autoimmune diseases. In multivariable analysis, female sex, older age, presence of hypertension and recurrent kidney injury were independent risk factors for worse renal outcomes. Conclusions: Our data demonstrate that autoimmune-related ATIN may present with systemic manifestations after kidney injury and is, therefore, commonly misdiagnosed. Repeated kidney injury is not uncommon in patients with ATIN. Scheduled follow-up is, therefore, critical for defining the exact etiology and proper management of ATIN. PMID- 28992225 TI - A guideline for leaf senescence analyses: from quantification to physiological and molecular investigations. AB - Leaf senescence is not a chaotic breakdown but a dynamic process following a precise timetable. It enables plants to economize with their resources and control their own viability and integrity. The onset as well as the progression of leaf senescence are co-ordinated by a complex genetic network that continuously integrates developmental and environmental signals such as biotic and abiotic stresses. Therefore, studying senescence requires an integrative and multi-scale analysis of the dynamic changes occurring in plant physiology and metabolism. In addition to providing an automated and standardized method to quantify leaf senescence at the macroscopic scale, we also propose an analytic framework to investigate senescence at physiological, biochemical, and molecular levels throughout the plant life cycle. We have developed protocols and suggested methods for studying different key processes involved in senescence, including photosynthetic capacities, membrane degradation, redox status, and genetic regulation. All methods presented in this review were conducted on Arabidopsis thaliana Columbia-0 and results are compared with senescence-related mutants. This guideline includes experimental design, protocols, recommendations, and the automated tools for leaf senescence analyses that could also be applied to other species. PMID- 28992224 TI - Modulation of leucocytic angiotensin-converting enzymes expression in patients maintained on high-permeable haemodialysis. AB - Background: High mortality of haemodialysis patients is associated with systemic chronic inflammation and overactivation of the renin-angiotensin system (RAS). Insufficient elimination of pro-inflammatory immune mediators, especially in the molecular weight range of 15-45 kDa, may be one of the reasons for this. Employment of haemodialysis membranes with increased permeability was shown to ameliorate the inflammatory response and might modulate the effects of local RAS. In this study, we tested the impact of high cut-off (HCO), medium cut-off (MCO) and high-flux (HF) dialysis on leucocytic transcripts of angiotensin-converting enzymes (ACE and ACE2). Additionally, the impact of HCO, MCO and HF sera and dialysates on local ACEs and inflammation markers was tested in THP-1 monocytes. Methods: Patients' leucocytes were obtained from our recent clinical studies comparing HCO and MCO dialysers with HF. The cells were subjected to quantitaive polymerase chain reaction (qPCR) analyses with TaqMan probes specific for ACE, ACE2 and angiotensin II (AngII) and Ang1-7 receptors. Sera and dialysates from the clinical trials as well as samples from in vitro dialysis were tested on THP 1 monocytic cells. The cells were subjected to qPCR analyses with TaqMan probes specific for ACE, ACE2, interleukin-6 and tumour necrosis factor alpha and immunocytochemistry with ACE and ACE2 antibodies. Results: Leucocytes obtained from patients treated with HCO or MCO demonstrated decreased transcript expression of ACE, while ACE2 was significantly upregulated as compared with HF. Receptors for AngII and Ang1-7 remained unchanged. THP-1 monocytes preconditioned with HCO and MCO patients' or in vitro dialysis sera reflected the same expressional regulation of ACE and ACE2 as those observed in HCO and MCO leucocytes. As a complementary finding, treatment with HCO and MCO in vitro dialysates induced a pro-inflammatory response of the cells as demonstrated by elevated messenger RNA expression of tumour necrosis factor alpha and interleukin 6, as well as upregulation of ACE and decreased levels of ACE2. Conclusions: Taken together, these data demonstrate that employment of membranes with high permeability eliminates a spectrum of mediators from circulation that affect the RAS components in leucocytes, especially ACE/ACE2. PMID- 28992226 TI - Arginine Vasotocin and Neuropeptide Y Vary with Seasonal Life-History Transitions in Garter Snakes. AB - Transitions between life-history stages are often accompanied by dramatic behavioral switches that result from a shift in motivation to pursue one resource over another. While the neuroendocrine mechanisms that regulate such behavioral transitions are poorly understood, arginine vasotocin (AVT) and neuropeptide Y (NPY) are excellent candidates because they modulate reproductive and feeding behavior, respectively. We asked if seasonal changes in AVT and NPY are concomitant with the seasonal migration to and from the feeding grounds in red sided garter snakes (Thamnophis sirtalis parietalis). Male and female snakes were collected in different migratory states during both the spring and fall. The total number of AVT- and NPY-immunoreactive (ir) cells was then quantified in each brain region of interest. To correct for potential variation in region volume related to sexually dimorphic body size in this species, we first determined that snout-vent length is an accurate proxy for regional brain volume. We then corrected each individual's ir cell number by its SVL to directly compare seasonal changes in AVT and NPY between males and females. Within the supraoptic nucleus, both males and females had more AVT-ir cells during the fall compared with spring. As predicted, males had significantly more AVT-ir cells during the spring mating season in the hypothalamus (HYP) and bed nucleus of the stria terminalis, brain regions important in regulating reproductive behavior. Females also had significantly more AVT-ir cells in the HYP during the spring, as well as a significantly higher number of hypothalamic AVT cells than males. During the fall, males had significantly more NPY-ir cells in the cortex and posterior HYP compared with spring, possibly reflecting increased feeding behavior during summer foraging. Females did not exhibit significant main effects of season on NPY-ir cell number in any region. Neither AVT- nor NPY-ir cell number varied significantly with migratory status, but we did observe significant changes related to seasonal transitions in reproductive state. Our results indicate that changes in brain AVT and NPY are associated with seasonal transitions in reproductive and foraging behaviors, and may be involved in mediating sex differences in the timing of life-history events. PMID- 28992227 TI - Pluripotency and a secretion mechanism of Drosophila transglutaminase. AB - Transglutaminase (TG) catalyses the formation of an isopeptide bond between glutamine and lysine residues and amine incorporation into specific glutamine residues. TG is conserved in all metazoans and functions both intracellularly and extracellularly. Here we review the existing knowledge of Drosophila TG with an emphasis on its pluripotency: Drosophila TG (i) plays a key role in cuticular morphogenesis, haemolymph coagulation, and entrapment against invading pathogens, (ii) suppresses the immune deficiency pathway to enable immune tolerance against commensal bacteria through the incorporation of polyamines into the nuclear factor-kappaB-like transcription factor Relish as well as through the protein protein cross-linking of Relish, (iii) forms a physical matrix in the gut through cross-linking of chitin-binding proteins and (iv) is involved in the maintenance of homeostasis in microbiota in the gut. Moreover, we review the evidence that TG A, one of alternative splicing-derived isoforms of Drosophila TG, is secreted through an endoplasmic reticulum/Golgi-independent pathway involving exosomes and fatty acylations. PMID- 28992228 TI - Three-dimensional observations of morphology of low-angle boundaries in ultra-low carbon lath martensite. AB - The lath martensite structure contains hierarchical substructures, such as blocks, packets and prior austenite grains. Generally, high-angle grain boundaries in the lath martensite structure, i.e. block boundaries, are correlated to mechanical properties. On the other hand, low-angle grain boundaries play an important role in morphological development. However, it is difficult to understand their nature because of the difficulty associated with the characterization of the complex morphologies by two-dimensional techniques. This study aims to identify the morphologies of low-angle boundaries in ultra-low carbon lath martensite. A serial-sectioning method and electron backscatter diffraction analysis are utilized to reconstruct three-dimensional objects and analyse their grain boundaries. A packet comprizes two low-angle grain boundaries - sub-block and fine packet boundaries. Sub-blocks exhibit porous morphology, with two large sub-blocks predominantly occupying a block. Several fine packets with different habit planes from the surrounding regions are observed. Fine packets are present in blocks, which frequently share a close-packed direction with the neighbouring fine packets. In addition, fine packets are in contact with the sub-block boundaries. PMID- 28992230 TI - Social Cognition and the Neurobiology of Rodent Mate Choice. AB - Various aspects of sociality, including mate choice, are dependent on social information. Mate choice is a social cognitive process that encompasses mechanisms for acquiring, processing, retaining and acting on social information. Social cognition includes the acquisition of social information about others (i.e., social recognition) and social information from others (i.e., social learning). Social cognition involves both assessing other individuals and their condition (e.g., health, infection status) and deciding about when and how to interact with them, thus, providing a frame-work for examining mate choice and its associated neurobiological mechanisms. In vertebrates, and in particular rodents, odors are an essential source of direct and indirect social information not only from others but also for others. Here, we briefly consider the relations between social cognition and olfactory-mediated mate choice in rodents. We briefly discuss aspects of: (1) social recognition of potential mates and the impact of infection threat on mate choice; (2) social learning and the utilization of the mate choices of others ("mate-choice copying") including in the context of infection; and (3) the neurobiological mechanisms, with particular focus on particular the roles of the nonapeptide, oxytocin and the steroid hormones, estrogens, associated with social cognition and mate choice. PMID- 28992229 TI - Meta-analysis of cognitive functioning in patients following kidney transplantation. AB - Background: There is mixed evidence regarding the nature of cognitive function in patients who have undergone renal transplantation. The aim of this meta-analysis was to examine which cognitive domains are impacted following kidney transplantation and how performance compares with non-transplanted patients or healthy controls/normative data. Method: A systematic search was conducted using keywords within three databases (Embase, MEDLINE and PsychINFO), yielding 458 unique studies, 10 of which met the inclusion criteria. Neuropsychological tests were grouped into nine cognitive domains and three separate analyses were undertaken within each domain: (i) within subjects pre- versus post-transplant, (ii) transplanted versus non-transplanted patients and (iii) transplanted versus healthy matched controls and standardized normative data. Results: Transplanted patients showed moderate to large improvements in the domains of general cognitive status (g = 0.526), information and motor speed (g = 0.558), spatial reasoning (g = 0.376), verbal memory (g = 0.759) and visual memory (g = 0.690) when compared with their pre-operative scores. Test scores in the same five domains were significantly better in post-transplanted patients when compared with dialysis-dependant or conservatively managed chronic kidney disease patients. However, post-transplanted patients' performance was significantly low compared with that of healthy controls (and standardized normative data) in the domains of executive functioning (g = -0.283), verbal fluency (g = -0.657) and language (g = -0.573). Conclusions: Two key issues arise from this review. First, domain-specific cognitive improvement occurs in patients after successful transplantation. Nevertheless, transplanted patients still performed significantly below healthy controls in some domains. Second, there are important shortcomings in existing studies; the length of follow-up is typically short and only limited neuropsychological test batteries are employed. These factors are important in order to support the recovery of cognitive function among patients following renal transplant. PMID- 28992231 TI - Triacylglycerol is produced from starch and polar lipids in the green alga Dunaliella tertiolecta. AB - The halotolerant green alga Dunaliella tertiolecta accumulates starch and triacylglycerol (TAG) amounting to 70% and 10-15% of total cellular carbon, respectively, when exposed to nitrogen (N) deprivation. The purpose of this study was to clarify the inter-relationships between the biosynthesis of TAG, starch, and polar lipids (PLs) in this alga. Pulse labeling with [14C]bicarbonate was utilized to label starch and [14C]palmitic acid (PlA) to label lipids. Transfer of 14C into TAG was measured and used to calculate rates of synthesis. About two thirds of the carbon in TAG originates from starch, and one-third is made de novo by direct CO2 assimilation. The level made from degradation of pre-formed PLs is estimated to be very small. Most of the de novo synthesis involves fatty acid transfer through PLs made during the first day of N deprivation. The results suggest that starch made by photosynthetic carbon assimilation at the early stages of N deprivation is utilized for synthesis of TAG. Trans-acylation from PLs is the second major contributor to TAG biosynthesis. The utilization of starch for TAG biosynthesis may have biotechnological applications to optimize TAG biosynthesis in algae. PMID- 28992232 TI - Development of a minipig physical phantom from CT data. AB - Quantification of pathological progression of radiation-induced injury is essential in development of treatment methods, and a proper animal model is necessary for relevant radiological and medical studies. A minipig is a current animal model selected because of its similarities to humans in anatomy and pathology. In the present study, a minipig physical phantom was developed using computed tomography (CT) data. For dosimetry purposes, the minipig physical phantom was constructed on a slice-by-slice basis, with an array of holes to accommodate dosimeters. The phantom is constituted of three major organs, i.e. bone, lung, and remaining soft tissue, and the organs are clearly distinguishable on each 20-mm-thick axial slice. The quality of the tissue-equivalent (TE) substitutes was analyzed in terms of the atomic compositions and Hounsfield units (HUs). The density (in g/cm3) and effective atomic number of TE substitutes for the bone, lung, and soft tissue are 1.4 and 7.9, 0.5 and 10.0, and 1.0 and 5.9, respectively. Although the TE substitutes have slightly different physical properties, we think the phantom is acceptable because the HU values of the TE substitutes lie in the HU range of real tissues. PMID- 28992233 TI - Boundary-artifact-free determination of potential distribution from differential phase contrast signals. AB - The differential phase contrast (DPC) imaging in STEM was mainly used for a study of magnetic material in a medium resolution. An ideal DPC signals give the center of mass of the diffraction pattern, which is proportional to an electric field. Recently, the possibility of the DPC imaging at atomic resolution was demonstrated. Thus, the DPC imaging opens up the possibility to observe the object phase that is proportional to the electrostatic potential.In this report we investigate the numerical procedures to obtain the object phase from the two perpendicular DPC signals. Specifically, we demonstrate that the discrete cosine transform (DCT) is the method to solve the Poisson equation, since we can use the Neumann boundary condition directly specified by the DPC signals. Furthermore, based on the fast Fourier transform (FFT) of an extended DPC signal we introduce the scheme that gives an equivalent result that is obtained with the DCT. The results obtained with the DCT and extended FFT method are superior to the results obtained with commonly used FFT. In addition, we develop real-time integration schemes that update the result with the progress of the scan. Our real-time integration gives the reasonable result, and can be used in a view mode. We demonstrate that our numerical procedures work excellently with the experimental DPC signals obtained from SrTiO3 single crystal. PMID- 28992234 TI - Pharmacologic management of diabetic retinopathy. AB - Diabetic retinopathy (DR) is a leading cause of vision loss in working-age populations, primarily attributable to retinal vascular hyperpermeability, hypoperfusion, and neoangiogenesis. In the past decade, laser photocoagulation and surgical interventions to treat DR have been replaced by topical administrations of anti-vascular endothelial growth factor drugs and corticosteroids. Although these drugs have revolutionized clinical management of DR, their limited efficacy and adverse effects have raised an increasing demand for new drug development. Meanwhile, mouse retinas have been prevalently employed as an experimental model system for angiogenic research, which has greatly contributed to the understanding of general principles in vascular biology. Therefore, clinical ophthalmology and basic research have complimentarily accumulated invaluable information for DR drug discovery. This review highlights the current pharmacologic management of DR, the utility of experimental mouse retinal models, and the perspectives on new drugs targeting the angioepoitin-Tie2 signals. PMID- 28992235 TI - Treatment by immunoadsorption for recurrent focal segmental glomerulosclerosis after paediatric kidney transplantation: a multicentre French cohort. AB - Background: Primary focal segmental glomerulosclerosis (FSGS) frequently recurs after kidney transplantation (KTx) in children. This can lead to delayed graft loss. As the management of children with recurrent FSGS is not well established, apheresis strategies could be a cornerstone to control the disease. Immunoadsorption (IA) is a recent apheresis therapy. There have been few studies examining IA in this setting. We report the results of IA for management of recurrent FSGS after KTx in children in France. Methods: We included all children treated with IA for early FSGS recurrence after KTx between January 2011 and June 2014 in France. We excluded genetic forms of FSGS. Patients' characteristics and technical data on IA were retrospectively collected. Recurrence was defined as nephrotic proteinuria during the post-transplantation period. Partial and complete remissions were defined when urine protein:creatinine ratios were less than 0.2 and 0.05 g/mmol, respectively. Results: Twelve patients, from six paediatric KTx units, presenting with FSGS recurrence between 0 and 21 days after KTx were treated with IA. Ten of 12 children were responders: 2 achieved partial remission and 8 complete remission. The decrease of proteinuria rapidly occurred within the first 10 sessions after initiating IA. After 3 months of IA, two patients maintained remission without IA and eight became IA dependent. No severe side effects were reported. Conclusions: Our study reports on the efficacy of IA in the recurrence of FSGS after KTx in children. Further prospective controlled studies are required to confirm these results and to optimize the management of FSGS recurrence after paediatric KTx. PMID- 28992236 TI - Bedroom Light Exposure at Night and the Incidence of Depressive Symptoms: A Longitudinal Study of the HEIJO-KYO Cohort. AB - Previous studies have indicated that minimal exposure to light at night (LAN) increases depression risk, even at 5 lux, in nocturnal and diurnal mammals. Although such low-level LAN may affect human circadian physiology, the association between exposure to LAN and depressive symptoms remains uncertain. In the present study, bedroom light intensity was measured objectively, and depressive symptoms were assessed, during 2010-2014 in Nara, Japan. Of 863 participants (mean age = 71.5 years) who did not have depressive symptoms at baseline, 73 participants reported development of depressive symptoms during follow-up (median, 24 months). Compared with the "dark" group (average of <5 lux; n = 710), the LAN group (average of >=5 lux; n = 153) exhibited a significantly higher depression risk (hazard ratio = 1.89; 95% CI: 1.13, 3.14), according to a Cox proportional hazards model adjusting for age, sex, body mass index, and economic status. Further, the significance remained in a multivariable model adjusting for hypertension, diabetes, and sleep parameters (hazard ratio = 1.72; 95% CI: 1.03, 2.89). Sensitivity analyses using bedroom light data with a cutoff value of >=10 lux suggested consistent results. In conclusion, these results indicated that exposure to LAN in home settings was independently associated with subsequent depression risk in an elderly general population. PMID- 28992238 TI - Anti-adhesive effects of plant wax coverage on insect attachment. AB - The long period of reciprocal antagonistic coevolution between some insect and plant species has led to the development of plant surface attributes that reduce insect attachment. These features serve as a defence against herbivores, sap sucking insects and nectar robbers, contribute to a temporary capture of insect pollinators, and prevent the escape of insects from traps of carnivorous plants. This review summarises the literature on attachment-mediated insect-plant interactions. A short introduction to attachment systems of insects is presented and the effect of three-dimensional epicuticular waxes on insect attachment is illustrated by many examples. Special attention is given to the mechanisms of the anti-attachment properties of plant wax structures (the roughness hypothesis, the contamination hypothesis, the fluid-adsorption hypothesis, and the wax-dissolving hypothesis) and their ecological implications. PMID- 28992237 TI - Impacts of Metabolic Syndrome Scores on Cerebrovascular Conductance Are Mediated by Arterial Stiffening. AB - BACKGROUND: Individuals with metabolic syndrome (MetS) exhibit reduced cerebral blood flow. The mechanisms of this reduction remain unknown but arterial stiffening has been implicated as a contributor. We determined if MetS was associated with reduced cerebral blood flow at midlife, and if so, whether arterial stiffness was responsible for mediating their relation. METHODS: Middle aged (40-60 years) community dwelling adults (n = 83) were studied. MetS score was calculated for each subject. Middle cerebral artery hemodynamics was measured using transcranial Doppler ultrasound. Indices of aortic, systemic, and carotid artery stiffness were derived. RESULTS: Subjects had subclinical MetS pathology (MetS score = 19.8 +/- 10.4) that was inversely associated with cerebrovascular conductance (CVC: r = -0.261, P = 0.02). Carotid-femoral pulse wave velocity (cfPWV) (r = -0.188, P = 0.09), brachial-ankle pulse wave velocity (baPWV) (r = 0.161, P = 0.15), and carotid artery distensibility (r = -0.10, P = 0.37) abrogated the direct association of MetS score and CVC, demonstrating full mediation. Nonparametric bootstrapping further indicated significant indirect effects of cfPWV, baPWV, and carotid artery distensibility, fully mediating reductions of CVC exerted from sublcinical MetS. Carotid artery distensibility demonstrated the greatest effect on CVC (B = -0.0019, SE = 0.0012, -0.0050 to 0.0002 95% confidence interval). CONCLUSIONS: Arterial stiffness, particularly the stiffness of the carotid artery, mediated reductions in CVC related to MetS. PMID- 28992239 TI - Investigation of the efficacy and safety of CyberKnife hypofractionated stereotactic radiotherapy for brainstem metastases using a new evaluation criterion: 'symptomatic control'. AB - The treatment of brainstem metastases remains a challenge as the brainstem itself is considered a neurological organ at risk. We aimed to investigate the efficacy and safety of CyberKnife hypofractionated stereotactic radiotherapy (HFSRT) for brainstem metastases, and to examine the balance between efficacy and safety for the management of neurological symptoms. A total of 26 lesions [pons (n = 18), medulla (n = 4) and midbrain (n = 4)] in 20 patients treated with CyberKnife hypofractionated stereotactic radiotherapy were retrospectively analyzed. The total radiation doses (18-30 Gy) were delivered in 3 or 5 equal fractions. The median follow-up was 6.5 (range, 0.5-38.0) months. The 6- and 12-month local control rates were 100% and 90%, respectively. Symptomatic failures, defined as the worsening and appearance of neurological symptoms due to the brainstem lesion after CyberKnife HFSRT, were observed in 6 patients [local failure (n = 1) and adverse events (n = 5). The symptomatic control and overall survival rates were 90% and 72% (after 6 months), respectively, and 76% and 53% (after 12 months), respectively. Longer symptomatic control was associated with site of lesion origin, and longer overall survival was associated with a graded prognostic assessment score of >2. To our knowledge, this is the second study to investigate the efficacy and safety of CyberKnife HFSRT for brainstem metastases. The local control rate was comparable with that of prior stereotactic radiosurgery studies. We propose a new evaluation criterion-'symptomatic control'-to evaluate the efficacy and safety of brainstem radiotherapy. PMID- 28992241 TI - Applicability of non-linear imaging in high-resolution transmission electron microscopy. AB - According to transmission cross-coefficient theory, the information limit of non linear imaging in high-resolution transmission electron microscopy is, under certain conditions, far beyond that of linear imaging, which suggests the possibility of using high-frequency information for structural determination. In this article, we studied the information beyond the linear information limit by means of multislice method simulation, with AlN as an example, and more structural information was obtained by using part of the high-frequency information. PMID- 28992240 TI - Alteration of molecular assembly of peroxiredoxins from hyperthermophilic archaea. AB - Peroxiredoxin from Pyrococcus horikoshii (PhPrx) is a decameric protein formed by ring-type assembly of five dimers. To engineer the quaternary structure of PhPrx, we created a mutant PhPrx (PhPrx6m) by introducing six point mutations designed to dissociate PhPrx into dimers. Although PhPrx6m was a dimer in solution, the six dimers assembled into a dodecamer following crystallization. In the crystal structure, PhPrx6m was overoxidized, and the peroxidatic cysteine was in sulfonic acid form and two cysteines in the C-terminal region were linked by an intramolecular disulfide bond. Thus, we characterized the wild-type PhPrx overoxidized by hydrogen peroxide (PhPrxPer). Analytical ultracentrifugation showed that PhPrxPer had a higher molecular mass in solution than PhPrx. This was confirmed by analysis of the crystal structure of PhPrxPer, which was found to form a ring-type dodecamer composed of six dimers. The monomeric structures of PhPrx6m and PhPrxPer differed from that of PhPrx in the relative orientation of two domains, reflecting the number of dimers in the ring-type assembly. Unlike PhPrx, homologous peroxiredoxin from Aeropyrum pernix (ApPrx) did not undergo hexameric association. This property can be explained by the stronger connection between the two domains in ApPrx due to its C-terminal extension relative to PhPrx. PMID- 28992242 TI - The Origin and Evolutionary Consequences of Skeletal Traits Shaped by Embryonic Muscular Activity, from Basal Theropods to Modern Birds. AB - Embryonic muscular activity (EMA) is involved in the development of several distinctive traits of birds. Modern avian diversity and the fossil record of the dinosaur-bird transition allow special insight into their evolution. Traits shaped by EMA result from mechanical forces acting at post-morphogenetic stages, such that genes often play a very indirect role. Their origin seldom suggests direct selection for the trait, but a side-effect of other changes such as musculo-skeletal rearrangements, heterochrony in skeletal maturation, or increased incubation temperature (which increases EMA). EMA-shaped traits like sesamoids may be inconstant, highly conserved, or even disappear and then reappear in evolution. Some sesamoids may become increasingly influenced in evolution by genetic-molecular mechanisms (genetic assimilation). There is also ample evidence of evolutionary transitions from sesamoids to bony eminences at tendon insertion sites, and vice-versa. This can be explained by newfound similarities in the earliest development of both kinds of structures, which suggest these transitions are likely triggered by EMA. Other traits that require EMA for their formation will not necessarily undergo genetic assimilation, but still be conserved over tens and hundreds of millions of years, allowing evolutionary reduction and loss of other skeletal elements. Upon their origin, EMA-shaped traits may not be directly genetic, nor immediately adaptive. Nevertheless, EMA can play a key role in evolutionary innovation, and have consequences for the subsequent direction of evolutionary change. Its role may be more important and ubiquitous than currently suspected. PMID- 28992243 TI - Mp1p homologues as virulence factors in Aspergillus fumigatus. AB - Recently, we showed that Mp1p is an important virulence factor of Talaromyces marneffei, a dimorphic fungus phylogenetically closely related to Aspergillus fumigatus. In this study, we investigated the virulence properties of the four Mp1p homologues (Afmp1p, Afmp2p, Afmp3p, and Afmp4p) in A. fumigatus using a mouse model. All mice died 7 days after challenge with wild-type A. fumigatus QC5096, AFMP1 knockdown mutant, AFMP2 knockdown mutant and AFMP3 knockdown mutant and 28 days after challenge with AFMP4 knockdown mutant (P<.0001). Only 11% of mice died 30 days after challenge with AFMP1-4 knockdown mutant (P<.0001). For mice challenge with AFMP1-4 knockdown mutant, lower abundance of fungal elements was observed in brains, kidneys, and spleens compared to mice challenge with QC5096 at day 4 post-infection. Fungal counts in brains of mice challenge with QC5096 or AFMP4 knockdown mutant were significantly higher than those challenge with AFMP1-4 knockdown mutant (P<.01 and P<.05). Fungal counts in kidneys of mice challenge with QC5096 or AFMP4 knockdown mutant were significantly higher than those challenge with AFMP1-4 knockdown mutant (P<.001 and P<.001) and those of mice challenge with QC5096 were significantly higher than those challenge with AFMP4 knockdown mutant (P<.05). There is no difference among the survival rates of wild-type A. fumigatus, AFMP4 knockdown mutant and AFMP1-4 knockdown mutant, suggesting that Mp1p homologues in A. fumigatus do not mediate its virulence via improving its survival in macrophage as in the case in T. marneffei. Afmp1p, Afmp2p, Afmp3p, and Afmp4p in combination are important virulence factors of A. fumigatus. PMID- 28992244 TI - LincRNA-1614 coordinates Sox2/PRC2-mediated repression of developmental genes in pluripotency maintenance. AB - Large-intergenic noncoding RNAs (lincRNAs) cooperate with core transcription factors to coordinate the pluripotency network of embryonic stem cells. The mechanisms by which lincRNAs affect chromatin structure and gene transcription remain mostly unknown. Here, we identified that a lincRNA (linc1614), occupied by pluripotency factors at its promoter, was indispensable for both maintenance and acquisition of pluripotency. Linc1614 served as a specific partner of core factor Sox2 in maintaining pluripotency, primarily by mediating the function of Sox2 in the repression of developmental genes. Moreover, Ezh2, an essential subunit of polycomb repressive complex 2 (PRC2), physically interacted with linc1614 and contributed to lincRNA-mediated transcriptional silencing. Thus, we propose that the interplay of linc1614 with Sox2 implicates this lincRNA as a recruitment platform that mediates transcriptional silencing by guiding the PRC2 complex to the loci of developmental genes. PMID- 28992245 TI - A Complex Lens for a Complex Eye. AB - A key innovation for high resolution eyes is a sophisticated lens that precisely focuses light onto photoreceptors. The eyes of holometabolous larvae range from very simple eyes that merely detect light to eyes that are capable of high spatial resolution. Particularly interesting are the bifocal lenses of Thermonectus marmoratus larvae, which differentially focus light on spectrally distinct retinas. While functional aspects of insect lenses have been relatively well studied, little work has explored their molecular makeup, especially in regard to more complex eye types. To investigate this question, we took a transcriptomic and proteomic approach to identify the major proteins contributing to the principal bifocal lenses of T. marmoratus larvae. Mass spectrometry revealed 10 major lens proteins. Six of these share sequence homology with cuticular proteins, a large class of proteins that are also major components of corneal lenses from adult compound eyes of Drosophila melanogaster and Anopheles gambiae. Two proteins were identified as house-keeping genes and the final two lack any sequence homologies to known genes. Overall the composition seems to follow a pattern of co-opting transparent and optically dense proteins, similar to what has been described for other animal lenses. To identify cells responsible for the secretion of specific lens proteins, we performed in situ hybridization studies and found some expression differences between distal and proximal corneagenous cells. Since the distal cells likely give rise to the periphery and the proximal cells to the center of the lens, our findings highlight a possible mechanism for establishing structural differences that are in line with the bifocal nature of these lenses. A better understanding of lens composition provides insights into the evolution of proper focusing, which is an important step in the transition between low-resolution and high-resolution eyes. PMID- 28992246 TI - Dietary Protein Intake and Early Menopause in the Nurses' Health Study II. AB - Early menopause, which is the cessation of ovarian function before age 45 years, affects 5%-10% of Western women and is associated with an increased risk of adverse health outcomes. Literature suggests that high levels of vegetable protein intake may prolong female reproductive function. We evaluated the association of long-term intake of vegetable protein, animal protein, and specific protein-rich foods with incidence of early natural menopause in the Nurses' Health Study II cohort. Women included in analyses (n = 85,682) were premenopausal at baseline (1991) and followed until 2011 for onset of natural menopause. Protein intake was assessed via food frequency questionnaire. In Cox proportional hazard models that were adjusted for age, smoking, body mass index, and other factors, women in the highest quintile of cumulatively averaged vegetable protein intake (median, 6.5% of calories) had a significant 16% lower risk of early menopause compared with women in the lowest quintile (3.9% of calories; 95% confidence interval: 0.73, 0.98; P for trend = 0.02). Intake of specific foods, including pasta, dark bread, and cold cereal, was also associated with lower risk (P < 0.05). Conversely, animal protein intake was unrelated to risk. High consumption of vegetable protein, equivalent to 3-4 servings per day of protein-rich foods, is associated with lower incidence of early menopause in US women. PMID- 28992247 TI - Physico-chemical properties of plant cuticles and their functional and ecological significance. AB - Most aerial plant surfaces are covered with a lipid-rich cuticle, which is a barrier for the bidirectional transport of substances between the plant and the surrounding environment. This review article provides an overview of the significance of the leaf cuticle as a barrier for the deposition and absorption of water and electrolytes. After providing insights into the physico-chemical properties of plant surfaces, the mechanisms of foliar absorption are revised with special emphasis on solutes. Due to the limited information and relative importance of the leaf cuticle of herbaceous and deciduous cultivated plants, an overview of the studies developed with Alpine conifers and treeline species is provided. The significance of foliar water uptake as a phenomenon of ecophysiological relevance in many areas of the world is also highlighted. Given the observed variability in structure and composition among, for example, plant species and organs, it is concluded that it is currently not possible to establish general permeability and wettability models that are valid for predicting liquid-surface interactions and the subsequent transport of water and electrolytes across plant surfaces. PMID- 28992249 TI - Association of dipstick hematuria with all-cause mortality in the general population: results from the specific health check and guidance program in Japan. AB - Background: Dipstick urine tests are used for general health screening in Japan. The effects of this screening on mortality have not been examined, especially with regard to hematuria. Methods: Subjects were those who participated in the 2008 Tokutei-Kenshin (nationwide specific health check and guidance program) in six districts in Japan. Using the national database of death certificates from 2008 to 2012, we identified subjects who might have died. We verified the candidates in collaboration with the regional National Health Insurance agency and public health nurses. Data were released to the research team supported by the Ministry of Health, Labor, and Welfare of Japan. Dipstick results of 1+ and higher were defined as hematuria (+). Hazard ratio (HR) [95% confidence interval (CI)] was calculated using the Cox proportional hazard analysis. Results: Among 112 115 subjects, we identified that 1290 had died by the end of 2012. In hematuria (-) subjects, the crude mortality rates were 1.2% (1.8% in men, 0.7% in women), whereas in hematuria (+) subjects, they were 1.1% (2.9% in men, 0.7% in women). After adjusting for age, body mass index, estimated glomerular filtration rate, proteinuria, comorbid condition (diabetes mellitus, hypertension and dyslipidemia), past history (stroke, heart disease and kidney disease) and lifestyle (smoking, drinking, walking and exercise), the HR (95% CI) for dipstick hematuria (+) in men was 1.464 (1.147-1.846; P = 0.003), whereas that for hematuria (-) was 0.820 (0.617-1.073; P = 0.151). Conclusions: Dipstick hematuria is significantly associated with mortality in men among Japanese community-based screening participants. PMID- 28992248 TI - Region-specific irradiation system with heavy-ion microbeam for active individuals of Caenorhabditis elegans. AB - Radiation may affect essential functions and behaviors such as locomotion, feeding, learning and memory. Although whole-body irradiation has been shown to reduce motility in the nematode Caenorhabditis elegans, the detailed mechanism responsible for this effect remains unknown. Targeted irradiation of the nerve ring responsible for sensory integration and information processing would allow us to determine whether the reduction of motility following whole-body irradiation reflects effects on the central nervous system or on the muscle cells themselves. We therefore addressed this issue using a collimating microbeam system. However, radiation targeting requires the animal to be immobilized, and previous studies have anesthetized animals to prevent their movement, thus making it impossible to assess their locomotion immediately after irradiation. We developed a method in which the animal was enclosed in a straight, microfluidic channel in a polydimethylsiloxane chip to inhibit free motion during irradiation, thus allowing locomotion to be observed immediately after irradiation. The head region (including the central nervous system), mid region around the intestine and uterus, and tail region were targeted independently. Each region was irradiated with 12 000 carbon ions (12C; 18.3 MeV/u; linear energy transfer = 106.4 keV/MUm), corresponding to 500 Gy at a phi20 MUm region. Motility was significantly decreased by whole-body irradiation, but not by irradiation of any of the individual regions, including the central nervous system. This suggests that radiation inhibits locomotion by a whole-body mechanism, potentially involving motoneurons and/or body-wall muscle cells, rather than affecting motor control via the central nervous system and the stimulation response. PMID- 28992251 TI - Resolving the Trade-off Between Visual Sensitivity and Spatial Acuity-Lessons from Hawkmoths. AB - The visual systems of many animals, particularly those active during the day, are optimized for high spatial acuity. However, at night, when photons are sparse and the visual signal competes with increased noise levels, fine spatial resolution cannot be sustained and is traded-off for the greater sensitivity required to see in dim light. High spatial acuity demands detectors and successive visual processing units whose receptive fields each cover only a small area of visual space, in order to reassemble a finely sampled and well resolved image. However, the smaller the sampled area, the fewer the photons that can be collected, and thus the worse the visual sensitivity becomes-leading to the classical trade-off between sensitivity and resolution. Nocturnal animals usually resolve this trade off in favour of sensitivity, and thus have lower spatial acuity than their diurnal counterparts. Here we review results highlighting how hawkmoths, a highly visual group of insects with species active at different light intensities, resolve the trade-off between sensitivity and spatial resolution. We compare adaptations both in the optics and retina, as well as at higher levels of neural processing in a nocturnal and a diurnal hawkmoth species, and also give a perspective on the behavioral consequences. We broaden the scope of our review by drawing comparisons with the adaptive strategies used by other nocturnal and diurnal insects. PMID- 28992250 TI - Equivalency of the quality of sublethal lesions after photons and high-linear energy transfer ion beams. AB - The quality of the sublethal damage (SLD) after irradiation with high-linear energy transfer (LET) ion beams was investigated with low-LET photons. Chinese hamster V79 cells and human squamous carcinoma SAS cells were first exposed to a priming dose of different ion beams at different LETs at the Heavy Ion Medical Accelerator in the Chiba facility. The cells were kept at room temperature and then exposed to a secondary test dose of X-rays. Based on the repair kinetics study, the surviving fraction of cells quickly increased with the repair time, and reached a plateau in 2-3 h, even when cells had received priming monoenergetic high-LET beams or spread-out Bragg peak beams as well as X-ray irradiation. The shapes of the cell survival curves from the secondary test X rays, after repair of the damage caused by the high-LET irradiation, were similar to those obtained from cells exposed to primary X-rays only. Complete SLD repairs were observed, even when the LET of the primary ion beams was very high. These results suggest that the SLD caused by high-LET irradiation was repaired well, and likewise, the damage caused by the X-rays. In cells where the ion beam had made a direct hit in the core region in an ion track, lethal damage to the domain was produced, resulting in cell death. On the other hand, in domains that had received a glancing hit in the low-LET penumbra region, the SLD produced was completely repaired. PMID- 28992252 TI - Uromodulin-SlpA binding dictates Lactobacillus acidophilus uptake by intestinal epithelial M cells. AB - Bacterial access to the gut immune system is a crucial process to promote host immune responses. The probiotic L-92 strain of Lactobacillus acidophilus exerts anti-allergic immunomodulatory effects upon oral administration in mice. Here, we show that microfold cells (M cells) are responsible for L-92 internalization for evoking L-92-mediated immune responses. L-92 specifically bound to uromodulin, a glycosylphosphatidylinositol-anchored protein expressed exclusively on M cells among intestinal epithelial cells. Internalization of L-92 into M cells was significantly reduced in uromodulin-deficient (Umod-/-) mice compared to Umod+/+ mice. Furthermore, the binding of L-92 to uromodulin was significantly decreased after removal of surface layer protein A (SlpA) from the bacteria. Our study thus revealed a crucial role of uromodulin on the M-cell surface for the uptake of SlpA-positive lactic acid bacteria into M cells, possibly leading to subsequent delivery of the bacteria to dendritic cells closely associated with M cells for immunomodulation. Our study also shed light on the possibility that SlpA and uromodulin could be used as vehicle and target, respectively, for efficient mucosal vaccine delivery. PMID- 28992253 TI - In vitro antifungal susceptibility patterns of planktonic and sessile Candida kefyr clinical isolates. AB - The activity of fluconazole, amphotericin B, caspofungin and micafungin was determined using XTT-based fungal damage assays against planktonic cells, early and mature biofilms of Candida kefyr. Median MICs of planktonic cells were 0.25 mg/l, 0.25 mg/l, 0.5 mg/l, and 0.06 mg/l for fluconazole, amphotericin B, caspofungin, and micafungin, respectively. Fluconazole showed at least 50% fungal damage at >=4 mg/l (51.5% +/- 6.63% to 78.38% +/- 1.44%) and at >=128 mg/l (57.88% +/- 9.2% to 67.25% +/- 9.59%), while amphotericin B produced an even higher anti-biofilm effect at >=0.5 mg/l (64.63% +/- 6.79% to 79.5% +/- 5.9%) and at >=0.12 mg/l (77.63% +/- 8.43% to 92.75% +/- 1.89%) against early and mature biofilms, respectively. In case of micafungin, 50% fungal damage was observed at >=0.06 mg/l (66.88% +/- 10.16% to 98.63% +/- 1.24%) and >=0.25 mg/l (74.13% +/- 10.77% to 99.38% +/- 0.38%) for early and mature biofilms, respectively. Caspofungin-exposed cells showed an unexpected susceptibility pattern, that is, planktonic cells showed significantly decreased susceptibility at concentrations ranging from 0.015 mg/l to 1 mg/l compared to biofilms (P < .05-.01). The damage in planktonic cells and biofilms was comparable at higher concentrations. For planktonic cells and biofilms, 50% fungal damage was observed first at 0.5 mg/l (59.75% +/- 3.16%) and at 0.06 mg/l (70.25% +/- 10.95%), respectively. This unexpected pattern was confirmed using scanning electron microscopy. The unusual susceptibility pattern observed at lower caspofungin concentrations may explain the poorer outcome of caspofungin-treated C. kefyr infections documented in certain patient populations. As this phenomenon was markedly less apparent in case of micafungin, these data suggest that micafungin may be a more reliable option than caspofungin for the treatment of C. kefyr infections. PMID- 28992254 TI - Latitudinal Clines in Temperature and Salinity Tolerance in Tidepool Copepods. AB - Local adaptation has been understudied in marine systems, but might be expected to be pronounced in the tidepool copepod Tigriopus californicus, which has a broad geographic range and extremely restricted dispersal. Tolerance to temperature and salinity was assessed in 14 populations over a 20 degrees latitudinal range. Adaptive differentiation to temperature and salinity was found at scales as low as 5.6 km. Latitudinal clines were significant, with northern populations being more tolerant of low salinity and less tolerant of high temperature and high salinity. Both temperature and salinity tolerance were more closely associated with long-term thermal maxima than with long-term precipitation data. Hyperthermal and hyposmotic tolerance were inversely correlated, a pattern that could potentially slow adaptation to future conditions. Together, these studies of intraspecific geographic patterns in resistance to multiple stressors are important in predicting how environmental change may effect range shifts and local extinctions. PMID- 28992255 TI - Plasma membrane-associated cation-binding protein 1-like protein negatively regulates intercellular movement of BaMV. AB - To establish a successful infection, a virus needs to replicate and move cell-to cell efficiently. We investigated whether one of the genes upregulated in Nicotiana benthamiana after Bamboo mosaic virus (BaMV) inoculation was involved in regulating virus movement. We revealed the gene to be a plasma membrane associated cation-binding protein 1-like protein, designated NbPCaP1L. The expression of NbPCaP1L in N. benthamiana was knocked down using Tobacco rattle virus-based gene silencing and consequently the accumulation of BaMV increased significantly to that of control plants. Further analysis indicated no significant difference in the accumulation of BaMV in NbPCaP1L knockdown and control protoplasts, suggesting NbPCaP1L may affect cell-to-cell movement of BaMV. Using a viral vector expressing green fluorescent protein in the knockdown plants, the mean area of viral focus, as determined by fluorescence, was found to be larger in NbPCaP1L knockdown plants. Orange fluorescence protein (OFP)-fused NbPCaP1L, NbPCaP1L-OFP, was expressed in N. benthamiana and reduced the accumulation of BaMV to 46%. To reveal the possible interaction of viral protein with NbPCaP1L, we performed yeast two-hybrid and co-immunoprecipitation experiments. The results indicated that NbPCaP1L interacted with BaMV replicase. The results also suggested that NbPCaP1L could trap the BaMV movement RNP complex via interaction with the viral replicase in the complex and so restricted viral cell-to-cell movement. PMID- 28992256 TI - On the relationship between epistasis and genetic variance heterogeneity. AB - Epistasis and genetic variance heterogeneity are two non-additive genetic inheritance patterns that are often, but not always, related. Here we use theoretical examples and empirical results from earlier analyses of experimental data to illustrate the connection between the two. This includes an introduction to the relationship between epistatic gene action, statistical epistasis, and genetic variance heterogeneity, and a brief discussion about how genetic processes other than epistasis can also give rise to genetic variance heterogeneity. PMID- 28992257 TI - Glomerular function in relation to circulating adhesion molecules and inflammation markers in a general population. AB - Background: Inflammation is a hallmark of chronic kidney disease (CKD) and stimulates glomerular expression of vascular adhesion molecules (VCAMs). We investigated in a general population whether estimated glomerular filtration rate (eGFR) is associated with circulating adhesion molecules, inflammation markers or both. Methods: We measured serum levels of five adhesion molecules [VCAM-1, intracellular adhesion molecule-1 (ICAM-1), P-selectin, E-selectin and monocyte chemoattractant protein-1 (MCP-1)] and seven inflammation markers [C-reactive protein (CRP), neutrophil gelatinase-associated lipocalin (NGAL), tumour necrosis factor receptor 1 (TNF-R1), TNF-alpha, interleukin 6 (IL-6), IL-8 and vascular endothelial growth factor] in 1338 randomly recruited people (50.8% women, mean age 51.7 years, eGFR 79.9 mL/min/1.73 m2). Results: In multivariable-adjusted analyses, eGFR decreased (P <= 0.004) with higher VCAM-1 (association size expressed in mL/min/1.73 m2 for a doubling of the marker, -2.99), MCP-1 (-1.19), NGAL (-1.19), TNF receptor 1 (-2.78), TNF-alpha (-2.28) and IL-6 (-0.94). The odds ratios of having eGFR <60 versus >=60 mL/min/1.73 m2 (n = 138 versus 1200) were significant (P <= 0.001) for VCAM-1 (1.77), MCP-1 (1.32), NGAL (1.26), TNF R1 (1.49), TNF-alpha (1.45) and IL-6 (1.20). Compared with 24-h albuminuria, VCAM 1 increased (P <0.0001) the area under the curve from 0.57 to 0.65, MCP-1 to 0.67 and TNF-R1 to 0.79, but TNF-R1 outperformed both adhesion molecules (P < 0.0001). Conclusions: In a general population, eGFR is inversely associated with circulating adhesion molecules VCAM-1 and MCP-1 and several inflammation markers, but inflammation markers, in particular TNF-R1 and TNF-alpha, identify patients with eGFR <60 mL/min/1.73 m2 more accurately. PMID- 28992258 TI - Risk and complications of venous thromboembolism in dialysis patients. AB - Background: Contemporary data on venous thromboembolism (VTE) risk in dialysis patients are limited. Our objective was to determine the risk and complications of VTE among incident maintenance dialysis patients. Methods: We performed a retrospective cohort study using administrative databases. We included adult incident dialysis patients from 2004 to 2010 (n = 13 315). Dialysis patients were age- and sex-matched to individuals of the general population using a 1:4 ratio (n = 53 260). We determined the 3-year cumulative incidence and incidence rate (IR) of VTE, pulmonary embolism (PE) and deep venous thrombosis (DVT). We examined outcomes of bleeding and all-cause mortality following a VTE event among matched dialysis patients who did and did not experience a VTE. We used Cox proportional hazards regression models, stratified on matched sets, to calculate the hazard ratios (HRs) for all outcomes of interest. Results: VTE occurred in 1114 (8.4%) dialysis patients compared with 1233 (2.3%) individuals in the general population {IR 37.1 versus 8.1 per 1000 person-years; HR 4.5 [95% confidence interval (CI) 4.1-4.9]; adjusted HR 2.9 (95% CI 2.6-3.4)}. Both components of VTE [PE and DVT; adjusted HR 4.0 (95% CI 2.9-5.6) and HR 2.8 (95% CI 2.4-3.2), respectively] occurred more frequently in dialysis patients. Compared with dialysis patients without a VTE, those with a VTE had a higher risk of bleeding [adjusted HR 2.0 (95% CI 1.3-2.9)] and all-cause mortality [adjusted HR 2.4 (95% CI 2.0-2.8)]. Conclusions: VTE is common in dialysis patients and confers a high risk of major bleeding and all-cause mortality. Thromboprophylaxis and VTE treatment studies in dialysis patients are needed. PMID- 28992259 TI - WGSSAT: A High-Throughput Computational Pipeline for Mining and Annotation of SSR Markers From Whole Genomes. AB - Mining and characterization of Simple Sequence Repeat (SSR) markers from whole genomes provide valuable information about biological significance of SSR distribution and also facilitate development of markers for genetic analysis. Whole genome sequencing (WGS)-SSR Annotation Tool (WGSSAT) is a graphical user interface pipeline developed using Java Netbeans and Perl scripts which facilitates in simplifying the process of SSR mining and characterization. WGSSAT takes input in FASTA format and automates the prediction of genes, noncoding RNA (ncRNA), core genes, repeats and SSRs from whole genomes followed by mapping of the predicted SSRs onto a genome (classified according to genes, ncRNA, repeats, exonic, intronic, and core gene region) along with primer identification and mining of cross-species markers. The program also generates a detailed statistical report along with visualization of mapped SSRs, genes, core genes, and RNAs. The features of WGSSAT were demonstrated using Takifugu rubripes data. This yielded a total of 139 057 SSR, out of which 113 703 SSR primer pairs were uniquely amplified in silico onto a T. rubripes (fugu) genome. Out of 113 703 mined SSRs, 81 463 were from coding region (including 4286 exonic and 77 177 intronic), 7 from RNA, 267 from core genes of fugu, whereas 105 641 SSR and 601 SSR primer pairs were uniquely mapped onto the medaka genome. WGSSAT is tested under Ubuntu Linux. The source code, documentation, user manual, example dataset and scripts are available online at https://sourceforge.net/projects/wgssat nbfgr. PMID- 28992261 TI - Randomized Trial of 2 Versus 1 Dose of Measles Vaccine: Effect on Hospital Admission of Children After 9 Months of Age. AB - Background: Two doses of measles vaccine (MV) might reduce the nonmeasles mortality rate more than 1 dose of MV does. The effect of 2 versus 1 dose on morbidity has not been examined. Within a randomized trial of the effect of 2 doses versus 1 dose of MV on mortality in Guinea-Bissau, we investigated the effect on hospital admissions. Methods: Children were randomly assigned 1:2 to receive MV at 4.5 and 9 months of age or the currently recommended dose at 9 months. We compared hospital admission rates among children between 9 and 18 months of age in a Cox regression model with age as the underlying time scale. Half of the children had received neonatal vitamin A supplementation (NVAS) in another trial. The beneficial effect of MV at 4.5 and 9 months on mortality was limited to children who had not received NVAS; therefore, we investigated the interaction of MV with NVAS on admission rates. Results: Among 5626 children (2 doses of MV, 1960 children; 1 dose of MV, 3666), we identified 311 hospital admissions of children between 9 and 18 months of age. Overall, compared to 1 dose of MV, 2 doses reduced the risk of hospital admission for children who had not received NVAS (hazard ratio [HR], 0.66 [95% confidence interval (CI), 0.47 0.93]), but we found no effect among NVAS recipients (HR, 1.16 [95% CI, 0.82 1.63]) (P = .02 for interaction). Conclusions: The benefit of 2 doses of MV was limited to children who had not received NVAS. NVAS is not generally recommended; hence, an early 2-dose measles vaccination policy might reduce hospital admissions more than the current policy of providing the first MV at 9 months of age. Trial registration: ClinicalTrials.gov identifier NCT00168558. PMID- 28992260 TI - Simulations of CYP51A from Aspergillus fumigatus in a model bilayer provide insights into triazole drug resistance. AB - Azole antifungal drugs target CYP51A in Aspergillus fumigatus by binding with the active site of the protein, blocking ergosterol biosynthesis. Resistance to azole antifungal drugs is now common, with a leucine to histidine amino acid substitution at position 98 the most frequent, predominantly conferring resistance to itraconazole, although cross-resistance has been reported in conjunction with other mutations. In this study, we create a homology model of CYP51A using a recently published crystal structure of the paralog protein CYP51B. The derived structures, wild type, and L98H mutant are positioned within a lipid membrane bilayer and subjected to molecular dynamics simulations in order improve the accuracy of both models. The structural analysis from our simulations suggests a decrease in active site surface from the formation of hydrogen bonds between the histidine substitution and neighboring polar side chains, potentially preventing the binding of azole drugs. This study yields a biologically relevant structure and set of dynamics of the A. fumigatus Lanosterol 14 alpha-demethylase enzyme and provides further insight into azole antifungal drug resistance. PMID- 28992262 TI - A matrix-assisted laser desorption/ionization time of flight mass spectrometry reference database for the identification of Histoplasma capsulatum. AB - The isolation of the pathogenic fungus Histoplasma capsulatum from cultures together with the visualization of typical intracellular yeast in tissues are the gold standard methods for diagnosis of histoplasmosis. However, cultures are time consuming, require level 3 containment and experienced personnel, and usually call for an additional confirmation test. Matrix-Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry (MALDI-ToF MS) has been established as a suitable tool for microbial identification in several clinical laboratories. A reference database has been constructed for the identification of H. capsulatum by MALDI-ToF MS by using six H. capsulatum strains previously identified by molecular methods. For validation, 63 fungal strains belonging to the Collection of the Spanish National Centre for Microbiology were tested against the new reference database combined with other commercial and in-house databases. In a blind assay, all H. capsulatum strains (n = 30) were correctly identified by the database and 86.6% had scores above 1.7. Considering both phases of the fungus for the same strain, the most reliable results were obtained with the mycelial phase, with only 13.3% of isolates having scores below 1.7. The new database was able to identify both morphological phases of the fungus. MALDI-ToF technology yields a prompt and simple identification from H. capsulatum yeast forms and early mycelial cultures. It allows for reducing response time and decreasing risk in fungus manipulation. PMID- 28992263 TI - Desphospho-uncarboxylated matrix Gla protein is a novel circulating biomarker predicting deterioration of renal function in the general population. AB - Background: Recent studies showing an inverse association between estimated glomerular filtration rate (eGFR), a microvascular trait, and inactive desphospho uncarboxylated matrix Gla protein (dp-ucMGP) support the hypothesis that after vitamin K-dependent activation, matrix Gla protein (MGP) is renoprotective, but these were limited by their cross-sectional design. Methods: In 1009 randomly recruited Flemish (50.6% women), we assessed the association between eGFR and plasma dp-ucMGP, using multivariable-adjusted analyses. Results: From baseline to follow-up 8.9 years later (median), dp-ucMGP increased by 23.0% whereas eGFR decreased by 4.05 mL/min/1.73 m2 (P < 0.001). In 938 participants with baseline eGFR >=60 mL/min/1.73 m2, the incidence of eGFR <60 mL/min/1.73 m2 at follow-up was 8.0% versus 4.1% in the top versus the bottom halve of baseline dp-ucMGP. For a 5-fold higher plasma dp-ucMGP at baseline, eGFR at follow-up decreased by 3.15 mL/min/1.73 m2 [95% confidence interval (CI) 1.26-5.05; P = 0.001]. The hazard ratio expressing the risk of progression to eGFR <60 mL/min/1.73 m2 was 3.49 (95% CI 1.45-8.40; P = 0.005). The hazard ratio relating the presence of microalbuminuria at follow-up to baseline dp-ucMGP was 4.70 (95% CI 1.57-14.1; P = 0.006). Conclusions: In conclusion, circulating inactive dp-ucMGP, a biomarker of poor vitamin K status, predicts renal dysfunction. Possible underlying mechanisms include protection by activated MGP against calcification and inhibition of the bone morphogenetic protein-signalling pathway. PMID- 28992264 TI - Proteasome 26S subunit PSMD1 regulates breast cancer cell growth through p53 protein degradation. AB - Endocrine therapy using antiestrogens and aromatase inhibitors is usually efficient to treat patients with hormone-sensitive breast cancer. Many patients with endocrine therapy, however, often acquire resistance. In the present study, we performed functional screening using short hairpin RNA library to dissect genes involved in antiestrogen tamoxifen resistance in MCF-7 breast cancer cells. We identified seven candidate genes that are associated with poor prognosis of breast cancer patients based on clinical dataset. The expression levels of six out of seven genes were higher in 4-hydroxytamoxifen (OHT) resistant MCF-7 (OHTR) cells compared with parental MCF-7 cells. Among the six selected genes, siRNA mediated knockdown of PSMD1 and TSPAN12 markedly reduced the proliferation of OHTR cells. Notably, the knockdown of proteasome 26S subunit PSMD1 exhibited cell cycle arrest and the accumulation of p53 protein through inhibiting p53 protein degradation. In accordance with p53 accumulation, its target genes p21 and SFN were also upregulated by PSMD1 silencing. Taken together, PSMD1 was identified as a potential gene that plays a role in the development of tamoxifen resistance in breast cancer cells. These findings will provide a new insight for the mechanism underlying endocrine therapy resistance and a prognostic and therapeutic molecular target for advanced breast cancer. PMID- 28992265 TI - Treatment With Quadrivalent Human Papillomavirus Vaccine for Juvenile-Onset Recurrent Respiratory Papillomatosis: Case Report and Review of the Literature. AB - Although juvenile-onset recurrent respiratory papillomatosis (JoRRP) generally involves a benign tumor on the larynx and other respiratory tract areas, almost all patients with this disease require repeated surgical intervention (to prevent airway obstruction during the course of illness) and various adjuvant therapies such as interferon, cidofovir, acyclovir, ribavirin, indole-3-carbinol, HspE7, mumps vaccine, photodynamic therapy, propranolol, cimetidine, and bevacizumab. Some case reports recently described the effectiveness of the quadrivalent human papillomavirus vaccine (HPV4) as an adjuvant therapy. On the basis of these reports, we administered HPV4 to a 2-year-old boy with JoRRP. However, no therapeutic effect was found. A review of the available literature revealed that current evidence for the effectiveness of therapeutic HPV4 and other adjuvant therapies for JoRRP is inconsistent. Therefore, the prophylactic use of currently available HPV vaccine for adolescents is the most effective strategy for preventing not only anogenital cancers but also genital warts, which might be a risk factor for JoRRP among their children in the future. PMID- 28992266 TI - Lateral root formation and the multiple roles of auxin. AB - Root systems can display variable architectures that contribute to survival strategies of plants. The model plant Arabidopsis thaliana possesses a tap root system, in which the primary root and lateral roots (LRs) are major architectural determinants. The phytohormone auxin fulfils multiple roles throughout LR development. In this review, we summarize recent advances in our understanding of four aspects of LR formation: (i) LR positioning, which determines the spatial distribution of lateral root primordia (LRP) and LRs along primary roots; (ii) LR initiation, encompassing the activation of nuclear migration in specified lateral root founder cells (LRFCs) up to the first asymmetric cell division; (iii) LR outgrowth, the 'primordium-intrinsic' patterning of de novo organ tissues and a meristem; and (iv) LR emergence, an interaction between LRP and overlaying tissues to allow passage through cell layers. We discuss how auxin signaling, embedded in a changing developmental context, plays important roles in all four phases. In addition, we discuss how rapid progress in gene network identification and analysis, modeling, and four-dimensional imaging techniques have led to an increasingly detailed understanding of the dynamic regulatory networks that control LR development. PMID- 28992267 TI - White blood cell fractions correlate with lesions of diabetic kidney disease and predict loss of kidney function in Type 2 diabetes. AB - Background: Inflammation linked to diabetic kidney disease (DKD) may affect white blood cell (WBC) counts and differentials. We examined the cross-sectional associations of total WBC count and WBC fractions with structural lesions of DKD in 108 Pima Indians with Type 2 diabetes who underwent research kidney biopsies. We also examined the longitudinal association of these WBC variables with renal function loss (RFL) in 941 Europeans with Type 2 diabetes from the SURDIAGENE study. Methods: Associations of WBC variables with morphometric parameters were assessed by linear regression. RFL was defined as>=40% loss of estimated glomerular filtration rate from baseline. Associations with RFL were evaluated by Cox regression. Hazard ratios (HRs) were reported per standard deviation increment of each WBC variable. Results: After multivariable adjustment, lymphocyte (r = -0.20, P = 0.043) and eosinophil (r = 0.21, P = 0.032) fractions in the Pima Indians correlated with glomerular basement membrane width. Eosinophil fraction also correlated with glomerular filtration surface density (r = -0.21, P = 0.031). Lymphocyte fraction (r = 0.25, P = 0.013), neutrophil fraction (r = -0.23, P = 0.021) and the neutrophil:lymphocyte ratio (r = -0.22, P = 0.024) correlated with percentage of normally fenestrated endothelial cells. During median follow-up of 4.5 years, 321 SURDIAGENE participants developed RFL. Lower lymphocyte fraction [HR = 0.67, 95% confidence interval (95% CI) 0.60-0.76] and higher neutrophil fraction (HR = 1.35, 95% CI 1.20-1.52), total WBC count (HR = 1.20, 95% CI 1.08-1.35) and neutrophil:lymphocyte ratio (HR = 1.44, 95% CI 1.28 1.62) each predicted RFL in this cohort. Conclusions: WBC fractions associate with morphometric lesions of DKD and predict RFL in individuals with Type 2 diabetes. PMID- 28992268 TI - Propranolol reduces reference-dependence in intertemporal choice. AB - In intertemporal choices between immediate and delayed rewards, people tend to prefer immediate rewards, often even when the delayed reward is larger. This is known as temporal discounting. It has been proposed that this tendency emerges because immediate rewards are more emotionally arousing than delayed rewards. However, in our previous research, we found no evidence for this but instead found that arousal responses (indexed with pupil dilation) in intertemporal choice are context-dependent. Specifically, arousal tracks the subjective value of the more variable reward option in the paradigm, whether it is immediate or delayed. Nevertheless, people tend to choose the less variable option in the choice task. In other words, their choices are reference-dependent and depend on variance in their recent history of offers. This suggests that there may be a causal relationship between reference-dependent choice and arousal, which we investigate here by reducing arousal pharmacologically using propranolol. Here, we show that propranolol reduces reference-dependence, leading to choices that are less influenced by recent history and more internally consistent. PMID- 28992269 TI - White matter correlates of psychopathic traits in a female community sample. AB - Psychopathy comprises interpersonal, affective, lifestyle and antisocial facets that vary dimensionally in the population and are associated with criminal offending and adverse psychosocial outcomes. Evidence associating these facets with white matter microstructure of the uncinate fasciculus and the cingulum tracts is inconsistent and derives principally from studies of male offenders. In a sample of 99 young women presenting a range of scores on the Psychopathy Checklist: Screening Version, we used Diffusion Tensor Imaging, tractography and Tract-Based Spatial Statistics to investigate microstructure across the brain and of the uncinate fasciculus and cingulum. Right uncinate fasciculus microstructure was negatively associated with the interpersonal facet, while cingulum integrity was not associated with any facet of psychopathy. Whole-brain analyses revealed that both affective and lifestyle facets were negatively correlated with white matter microstructure adjacent to the fusiform gyrus, and the interpersonal facet correlated negatively with the integrity of the fornix. Findings survived adjustment for the other facet scores, and age, verbal and performance IQ. A similar negative association between the interpersonal facet and uncinate fasciculus integrity was previously observed in male offenders. Thus, previous evidence showing that psychopathic traits are associated with functional and structural abnormalities within limbic networks may also apply to females. PMID- 28992270 TI - Neural activity during affect labeling predicts expressive writing effects on well-being: GLM and SVM approaches. AB - Affect labeling (putting feelings into words) is a form of incidental emotion regulation that could underpin some benefits of expressive writing (i.e. writing about negative experiences). Here, we show that neural responses during affect labeling predicted changes in psychological and physical well-being outcome measures 3 months later. Furthermore, neural activity of specific frontal regions and amygdala predicted those outcomes as a function of expressive writing. Using supervised learning (support vector machines regression), improvements in four measures of psychological and physical health (physical symptoms, depression, anxiety and life satisfaction) after an expressive writing intervention were predicted with an average of 0.85% prediction error [root mean square error (RMSE) %]. The predictions were significantly more accurate with machine learning than with the conventional generalized linear model method (average RMSE: 1.3%). Consistent with affect labeling research, right ventrolateral prefrontal cortex (RVLPFC) and amygdalae were top predictors of improvement in the four outcomes. Moreover, RVLPFC and left amygdala predicted benefits due to expressive writing in satisfaction with life and depression outcome measures, respectively. This study demonstrates the substantial merit of supervised machine learning for real world outcome prediction in social and affective neuroscience. PMID- 28992271 TI - Preschool negative emotionality predicts activity and connectivity of the fusiform face area and amygdala in later childhood. AB - Negative emotionality (NE) refers to individual differences in the propensity to experience and react with negative emotions and is associated with increased risk of psychological disorder. However, research on the neural bases of NE has focused almost exclusively on amygdala activity during emotional face processing. This study broadened this framework by examining the relationship between observed NE in early childhood and subsequent neural responses to emotional faces in both the amygdala and the fusiform face area (FFA) in a late childhood/early adolescent sample. Measures of NE were obtained from children at age 3 using laboratory observations, and functional magnetic resonance imaging (fMRI) data were collected when these children were between the ages of 9 and 12 while performing a visual stimulus identity matching task with houses and emotional faces as stimuli. Multiple regression analyses revealed that higher NE at age 3 is associated with significantly greater activation in the left amygdala and left FFA but lower functional connectivity between these two regions during the face conditions. These findings suggest that those with higher early NE have subsequent alterations in both activity and connectivity within an extended network during face processing. PMID- 28992272 TI - Neural predictors of emotional inertia in daily life. AB - Assessing emotional dynamics in the brain offers insight into the fundamental neural and psychological mechanisms underlying emotion. One such dynamic is emotional inertia-the influence of one's emotional state at one time point on one's emotional state at a subsequent time point. Emotion inertia reflects emotional rigidity and poor emotion regulation as evidenced by its relationship to depression and neuroticism. In this study, we assessed changes in cerebral blood flow (CBF) from before to after an emotional task and used these changes to predict stress, positive and negative emotional inertia in daily life events. Cerebral blood flow changes in the lateral prefrontal cortex (lPFC) predicted decreased non-specific emotional inertia, suggesting that the lPFC may feature a general inhibitory mechanism responsible for limiting the impact that an emotional state from one event has on the emotional state of a subsequent event. CBF changes in the ventromedial prefrontal cortex and lateral occipital cortex were associated with positive emotional inertia and negative/stress inertia, respectively. These data advance the blossoming literature on the temporal dynamics of emotion in the brain and on the use of neural indices to predict mental health-relevant behavior in daily life. PMID- 28992273 TI - Neural correlates of moral judgment in pedophilia. AB - Pedophilia is a sexual preference that is often associated with child sex offending (CSO). Sexual urges towards prepubescent children and specifically acting upon those urges are universally regarded as immoral. However, up until now, it is completely unknown whether moral processing of sexual offenses is altered in pedophiles. A total of 31 pedophilic men and 19 healthy controls were assessed by using functional magnetic resonance imaging (fMRI) in combination with a moral judgment paradigm consisting of 36 scenarios describing different types of offenses.Scenarios depicting sexual offenses against children compared to those depicting adults were associated with higher pattern of activation in the left temporo-parietal-junction (TPJ) and left posterior insular cortex, the posterior cingulate gyrus as well as the precuneus in controls relative to pedophiles, and vice versa. Moreover, brain activation in these areas were positively associated with ratings of moral reprehensibility and negatively associated with decision durations, but only in controls. Brain activation, found in key areas related to the broad network of moral judgment, theory of mind and (socio-)moral disgust - point to different moral processing of sexual offenses in pedophilia in general. The lack of associations between brain activation and behavioral responses in pedophiles further suggest a biased response pattern or dissected implicit valuation processes. PMID- 28992275 TI - Cautionary note: propensity score matching does not account for bias due to censoring. AB - This article gives a review of the limitations of propensity score matching as a tool for confounding control in the presence of censoring. Using an illustrative simulation study, we emphasize the importance of explicit adjustment for selective loss to follow-up and explain how this may be achieved. PMID- 28992274 TI - Nucleus accumbens shell moderates preference bias during voluntary choice behavior. AB - The nucleus accumbens (NAc) shell lies anatomically at a critical intersection within the brain's reward system circuitry, however, its role in voluntary choice behavior remains unclear. Rats with electrolytic lesions in the NAc shell were tested in a novel foraging paradigm. Over a continuous two-week period they freely chose among four nutritionally identical but differently flavored food pellets by pressing corresponding levers. We examined the lesion's effects on three behavioral dynamics components: motivation (when to eat), preference bias (what to choose) and persistence (how long to repeat the same choice). The lesion led to a marked increase in the preference bias: i.e., increased selection of the most-preferred choice option, and decreased selection of the others. We found no effects on any other behavioral measures, suggesting no effect on motivation or choice persistence. The results implicate the NAc shell in moderating the instrumental valuation process by inhibiting excessive bias toward preferred choice options. PMID- 28992276 TI - The Potential Role of Primary Care in Case Detection/Screening of Primary Aldosteronism. AB - Endocrine hypertension, particularly primary aldosteronism (PA), was previously considered to account for less than 1% of all hypertension and was suspected only when patients presented with spontaneous hypokalemia. However, the last 20 years of PA research has now clearly shown that PA is not a rarity, but rather, may account for up to 13% of unselected hypertensive individuals and between 10% and 20% of those with resistant hypertension. Most of these patients do not have spontaneous hypokalemia. The population prevalence of PA likely far exceeds actual detection rates in routine clinical care. As PA represents one of the most common, potentially reversible causes of hypertension, and is associated with significant cardiovascular complications over the long term, it is clear that a pragmatic strategy for targeted case detection in primary care is needed. PMID- 28992277 TI - Advances in abscission signaling. AB - Abscission is a process in plants for shedding unwanted organs such as leaves, flowers, fruits, or floral organs. Shedding of leaves in the fall is the most visually obvious display of abscission in nature. The very shape plants take is forged by the processes of growth and abscission. Mankind manipulates abscission in modern agriculture to do things such as prevent pre-harvest fruit drop prior to mechanical harvesting in orchards. Abscission occurs specifically at abscission zones that are laid down as the organ that will one day abscise is developed. A sophisticated signaling network initiates abscission when it is time to shed the unwanted organ. In this article, we review recent advances in understanding the signaling mechanisms that activate abscission. Physiological advances and roles for hormones in abscission are also addressed. Finally, we discuss current avenues for basic abscission research and potentially lucrative future directions for its application to modern agriculture. PMID- 28992278 TI - Auxin production as an integrator of environmental cues for developmental growth regulation. AB - Being sessile organisms, plants have evolved mechanisms allowing them to control their growth and development in response to environmental changes. This occurs by means of complex interacting signalling networks that integrate diverse environmental cues into co-ordinated and highly regulated responses. Auxin is an essential phytohormone that functions as a signalling molecule, driving both growth and developmental processes. It is involved in numerous biological processes ranging from control of cell expansion and cell division to tissue specification, embryogenesis, and organ development. All these processes require the formation of auxin gradients established and maintained through the combined processes of biosynthesis, metabolism, and inter- and intracellular directional transport. Environmental conditions can profoundly affect the plant developmental programme, and the co-ordinated shoot and root growth ought to be fine-tuned to environmental challenges such as temperature, light, and nutrient and water content. The key role of auxin as an integrator of environmental signals has become clear in recent years, and emerging evidence implicates auxin biosynthesis as an essential component of the overall mechanisms of plants tolerance to stress. In this review, we provide an account of auxin's role as an integrator of environmental signals and, in particular, we highlight the effect of these signals on the control of auxin production. PMID- 28992279 TI - Targeting new cellular disease pathways in autosomal dominant polycystic kidney disease. AB - Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited cause of end-stage renal failure. Understanding the molecular and cellular pathogenesis of ADPKD could help to identify new targets for treatment. The classic cellular cystic phenotype includes changes in proliferation, apoptosis, fluid secretion, extracellular matrix and cilia function. However, recent research, suggests that the cellular cystic phenotype could be broader and that changes, such as altered metabolism, autophagy, inflammation, oxidative stress and epigenetic modification, could play important roles in the processes of cyst initiation, cyst growth or disease progression. Here we review these newer cellular pathways, describe evidence for their possible links to cystic pathogenesis or different stages of disease and discuss the options for developing novel treatments. PMID- 28992280 TI - Plasma biomarkers improve prediction of diabetic kidney disease in adults with type 1 diabetes over a 12-year follow-up: CACTI study. AB - Background: The objective of the study was to determine whether plasma biomarkers of kidney injury improve the prediction of diabetic kidney disease (DKD) in adults with type 1 diabetes (T1D) over a period of 12 years. Methods: Participants (n = 527, 53% females) in the Coronary Artery Calcification in T1D (CACTI) Study were examined during 2002-04, at a mean (+/- standard deviation) age of 39.6 +/- 9.0 years with 24.8 years as the median duration of diabetes. Urine albumin-to-creatinine (ACR) and estimated glomerular filtration rate (eGFR) by CKD-EPI (chronic kidney disease epidemiology collaboration) creatinine were measured at the baseline and after mean follow-up of 12.1 +/- 1.5 years. Albuminuria was defined as ACR >=30 mg/g and impaired GFR as eGFR <60 mL/min/1.73 m2. Kidney injury biomarkers (Meso Scale Diagnostics) were measured on stored baseline plasma samples. A principal component analysis (PCA) identified two components: (i) kidney injury molecule-1, calbindin, osteoactivin, trefoil factor 3 and vascular endothelial growth factor; and (ii) beta-2 microglobulin, cystatin C, neutrophil gelatinase-associated lipocalin and osteopontin that were used in the multivariable regression analyses. Results: Component 2 of the PCA was associated with increase in log modulus ACR [beta +/- standard error (SE): 0.16 +/- 0.07, P = 0.02] and eGFR (beta +/- SE: -2.56 +/- 0.97, P = 0.009) over a period of 12 years after adjusting for traditional risk factors (age, sex, HbA1c, low-density lipoprotein cholesterol and systolic blood pressure and baseline eGFR/baseline ACR). Only Component 2 of the PCA was associated with incident impaired GFR (odds ratio 2.08, 95% confidence interval 1.18-3.67, P = 0.01), adjusting for traditional risk factors. The addition of Component 2 to traditional risk factors significantly improved C-statistics and net reclassification improvement for incident-impaired GFR (DeltaAUC: 0.02 +/- 0.01, P = 0.049, and 29% non-events correctly reclassified, P < 0.0001). Conclusions: Plasma kidney injury biomarkers can help predict development of DKD in T1D. PMID- 28992282 TI - Intraspecies variation in the efficacy of adjunctive recombinant interferon-gamma therapy against cryptococcal meningoencephalitis in mice. AB - The efficacy of recombinant interferon gamma (rIFN-gamma) for cryptococcal meningoencephalitis has been poorly understood. Compared to Cryptococcus gattii, rIFN-gamma significantly improved the survival in experimental meningoencephalitis due to Cryptococcus neoformans. The number of phagocytic macrophages and the levels of inflammatory cytokines production for ex vivo co incubation with C. neoformans were increased after rIFN-gamma stimulation but not C. gattii. Intraspecies differences of phagocytosis by the rIFN-gamma-activated macrophages might be associated to the severity of cryptococcal infection. PMID- 28992281 TI - A Return to Wisdom: Using Sickness Behaviors to Integrate Ecological and Translational Research. AB - Sickness is typically characterized by fever, anorexia, cachexia, and reductions in social, pleasurable, and sexual behaviors. These responses can be displayed at varying intensities both within and among individuals, and the adaptive nature of sickness responses can be demonstrated by the context-dependent nature of their expression. The study of sickness has become an important area of investigation for researchers in a wide range of areas, including psychoneuroimmunology (PNI) and ecoimmunology (EI). The general goal of PNI is to identify key interactions among the nervous, endocrine and immune systems and behavior, and how disruptions in these processes might contribute to disease states. EI, in turn, has been established more recently within the perspectives of ecology and evolutionary biology, and is aimed more at understanding natural variation in immune function and sickness responses within a broadly integrative, organismal, and evolutionary context. The goal of this review is to examine the literature on sickness from both basic and biomedical perspectives within PNI and EI and to demonstrate how the integrative study of sickness behavior can serve as an integrating agent to connect ecological and translational approaches to the study of disease. By focusing on a set of specific exemplars, including the energetics of sickness, social context, and environmental influences on sickness, we hope to accomplish the larger goal of developing a common synthetic framework to understand sickness from multiple levels of analysis and varying perspectives across the fields of PNI and EI. By applying this integrative approach to sickness, we will be able to develop a more comprehensive view of sickness as a suite of adaptive responses rather than the simply deleterious consequences of illness. PMID- 28992283 TI - The roles of the cuticle in plant development: organ adhesions and beyond. AB - Cuticles, which are composed of a variety of aliphatic molecules, impregnate epidermal cell walls forming diffusion barriers that cover almost all the aerial surfaces in higher plants. In addition to revealing important roles for cuticles in protecting plants against water loss and other environmental stresses and aggressions, mutants with permeable cuticles show major defects in plant development, such as abnormal organ formation as well as altered seed germination and viability. However, understanding the mechanistic basis for these developmental defects represents a significant challenge due to the pleiotropic nature of phenotypes and the altered physiological status/viability of some mutant backgrounds. Here we discuss both the basis of developmental phenotypes associated with defects in cuticle function and mechanisms underlying developmental processes that implicate cuticle modification. Developmental abnormalities in cuticle mutants originate at early developmental time points, when cuticle composition and properties are very difficult to measure. Nonetheless, we aim to extract principles from existing data in order to pinpoint the key cuticle components and properties required for normal plant development. Based on our analysis, we will highlight several major questions that need to be addressed and technical hurdles that need to be overcome in order to advance our current understanding of the developmental importance of plant cuticles. PMID- 28992284 TI - Plasma Homocysteine Levels Are Associated With Circadian Blood Pressure Variation in Chinese Hypertensive Adults. AB - BACKGROUND: Homocysteine-lowering intervention with folate was recently shown to be able to increase day-night difference of blood pressure (BP) in humans indicating a potential relationship between homocysteine and circadian BP variation. We thus sought to investigate the association between plasma total homocysteine level (tHcy) and circadian BP variation in hypertensive adults. METHODS: We enrolled 244 eligible dipping and 249 nondipping BP status adults from 560 adults who were randomly sampled from 5,233 Chinese hypertensive adults who received ambulatory BP monitoring (ABPM). We further enrolled 390 adults with CC/CT genotypes of the methylenetetrahydrofolate reductase (MTHFR) and 79 TT genotype who received ABPM at the same time from 1858 hypertensive adults with MTHFR polymorphisms detection. RESULTS: Plasma tHcy in nondippers was significantly higher than dippers (P < 0.001). Simple linear analysis revealed that tHcy significantly correlated with nocturnal systolic BP fall (r = -0.145, P = 0.001) and diastolic BP fall (r = -0.141, P = 0.002). Multivariate logistic regression analysis further identified tHcy as an independent factor correlated with the presence of nondipping BP status in hypertensive adults (odds ratio: 1.873, 95% confidence interval: 1.171-2.996, P = 0.009). The percentage of dipping BP status was 19.49% or 8.86% and the percentage of nondipping BP status was 80.51% or 91.14% in CC/CT or TT genotypes, respectively. The above different between CC/CT and TT genotypes was significant (P = 0.024). CONCLUSIONS: These results indicated that high homocysteine levels associate with disturbed circadian BP variation in Chinese hypertensive adults. PMID- 28992285 TI - Remote ischaemic preconditioning for renal and cardiac protection in adult patients undergoing cardiac surgery with cardiopulmonary bypass: systematic review and meta-analysis of randomized controlled trials. AB - Background: The main aim of this systematic review was to assess whether remote ischaemic preconditioning (RIPC) protects kidneys and the heart in cardiac surgery with cardiopulmonary bypass (CPB) and to investigate a possible role of anaesthetic agents. Methods: Randomized clinical trials (RCTs) on the effects of RIPC through limb ischaemia in adult patients undergoing cardiac surgery with CPB were searched (1965-October 2016) in PubMed, Cochrane Library and article reference lists. A random effects model on standardized mean difference (SMD) for continuous outcomes and the Peto odds ratio (OR) for dichotomous outcomes were used to meta-analyse data. Subgroup analyses to evaluate the effects of different anaesthetic regimens were pre-planned. Results: Thirty-three RCTs (5999 participants) were included. In the whole group, RIPC did not significantly reduce the incidence of acute kidney injury (AKI), acute myocardial infarction, atrial fibrillation, mortality or length of intensive care unit (ICU) and hospital stays. On the contrary, RIPC significantly reduced the area under the curve for myocardial injury biomarkers (MIBs) {SMD -0.37 [95% confidence interval (CI) -0.53 to - 0.21]} and the composite endpoint incidence [OR 0.85 (95% CI 0.74 0.97)]. In the volatile anaesthetic group, RIPC significantly reduced AKI incidence [OR 0.57 (95% CI 0.41-0.79)] and marginally reduced ICU stay. Conversely, except for MIBs, RIPC had fewer non-significant effects under propofol with or without volatile anaesthetics. Conclusions: RIPC did not consistently reduce morbidity and mortality in adults undergoing cardiac surgery with CPB. In the subgroup on volatile anaesthetics only, RIPC markedly and significantly reduced the incidence of AKI and composite endpoint as well as myocardial injury. PMID- 28992286 TI - Intracellular Recordings of Spectral Sensitivities in Stomatopods: a Comparison across Species. AB - Stomatopods (mantis shrimps) possess one of the most complex eyes in the world with photoreceptors detecting up to 12 different colors. It is not yet understood why stomatopods have almost four times the number of spectral photoreceptors compared with most other animals. It has, however, been suggested that these seemingly redundant photoreceptors could encode color through a new mechanism. Here we compare the spectral sensitivities across five species of stomatopods within the superfamily Gonodactyloidea using intracellular electrophysiological recordings. The results show that the spectral sensitivities across species of stomatopods are remarkably similar apart from some variation in the long wavelength receptors. We relate these results to spectral sensitivity estimates previously obtained using microspectrophotometry and discuss the variation in the spectral sensitivity maxima (lambdamax) of the long-wavelength receptors in regard to the previous findings that stomatopods are able to tune their spectral sensitivities according to their respective light environment. We further discuss the similarities of the spectral sensitivities across species of stomatopods in regard to how color information might be processed by their visual systems. PMID- 28992287 TI - New Insights into the Evolution of the W Chromosome in Lepidoptera. AB - Moths and butterflies (Lepidoptera) represent the most diverse group of animals with heterogametic females. Although the vast majority of species has a WZ/ZZ (female/male) sex chromosome system, it is generally accepted that the ancestral system was Z/ZZ and the W chromosome has evolved in a common ancestor of Tischeriidae and Ditrysia. However, the lack of data on sex chromosomes in lower Lepidoptera has prevented a formal test of this hypothesis. Here, we performed a detailed analysis of sex chromosomes in Tischeria ekebladella (Tischeriidae) and 3 species representing lower Ditrysia, Cameraria ohridella (Gracillariidae), Plutella xylostella (Plutellidae), and Tineola bisselliella (Tineidae). Using comparative genomic hybridization we show that the first 3 species have well differentiated W chromosomes, which vary considerably in their molecular composition, whereas T. bisselliella has no W chromosome. Furthermore, our results suggest the presence of neo-sex chromosomes in C. ohridella. For Z chromosomes, we selected 5 genes evenly distributed along the Z chromosome in ditrysian model species and tested their Z-linkage using qPCR. The tested genes (Henna, laminin A, Paramyosin, Tyrosine hydroxylase, and 6-Phosphogluconate dehydrogenase) proved to be Z-linked in all species examined. The conserved synteny of the Z chromosome across Tischeriidae and Ditrysia, along with the W chromosome absence in the lower ditrysian families Psychidae and Tineidae, suggests a possible independent origin of the W chromosomes in these 2 lineages. PMID- 28992288 TI - Erlotinib attenuates the progression of chronic kidney disease in rats with remnant kidney. AB - Background: Increasing evidence indicates that epidermal growth factor receptor (EGFR) has a pathogenic role in renal fibrosis. Currently no effective treatment can completely halt the progression of chronic kidney disease (CKD). This study was undertaken to investigate the renoprotective effects of erlotinib, a tyrosine kinase inhibitor that can block EGFR activity in the progression of CKD and the mechanisms involved. Methods: Sprague Dawley rats with 5/6 nephrectomy were administered either erlotinib or vehicle from 2 weeks after surgery and for a period of 8 weeks. Blood pressure, proteinuria and serum creatinine were measured periodically. Renal morphological investigations were performed at sacrifice. In vitro , we used normal human mesangial cells (NHMCs) and human proximal tubular cells to investigate the inhibitory effects of erlotinib on renal fibrosis associated signaling pathways by western blotting. Results: Erlotinib treatment significantly blunted the progression of CKD as evidenced by reduced levels of serum creatinine, proteinuria and renal cortical profibrogenic genes and scores of glomerulosclerosis and tubulointerstitial damage. Tubulointerstitial macrophage infiltration and multiple pro-inflammatory cytokine gene expression levels were also attenuated by erlotinib treatment. In vitro , heparin-binding epidermal growth factor-like growth factor-induced Akt and extracellular regulated kinase (ERK) 1/2 activation in normal human mesangial cells and human proximal tubular cells was inhibited by pretreatment with erlotinib. Conclusions: EGFR blocking by erlotinib protected against renal fibrosis in 5/6 nephrectomized rats via inhibition of Akt and ERK 1/2 signaling pathways, which are associated with renal fibrosis. Erlotinib also has anti-inflammatory properties, which may contribute to its renoprotective effects. Erlotinib represents a potential novel therapeutic strategy for the treatment of CKD. PMID- 28992289 TI - Transcriptomics in kidney biopsy is an untapped resource for precision therapy in nephrology: a systematic review. AB - Background: The diagnosis of glomerular diseases is based on the evaluation of histological lesions in renal tissue by means of light and electronic microscopy, and immunofluorescence technique. Frozen and archival formalin-fixed paraffin embedded kidney biopsies represent a stored resource for high-throughput technologies. Transcriptomics makes it possible to study the whole gene expression profile of cells and tissues in a specific period and/or condition. The results, whether considered alone or integrated with other omics data, could help to improve existing knowledge about the pathogenetic mechanisms of glomerulopathies. Methods: This review describes the molecular analysis of histological lesions obtained by transcriptomics in glomerular diseases, such as minimal change disease, focal and segmental glomerular sclerosis, IgA nephropathy, lupus nephritis and diabetic nephropathy. Results: Of 716 articles obtained through database searches, 19 relevant articles were considered for the systematic review. Transcriptomics in kidney biopsy from patients with glomerular diseases have generated new insights on a few promising genes, illustrated in each disease section, which may be considered important targets for the care of these diseases. Conclusions: Transcriptomics is an untapped resource for precision nephrology. Moreover, the integration of transcriptomics and systems pharmacology could predict the best drug combination to revert a pathological condition by targeting disease-specific molecular networks. PMID- 28992290 TI - Invasive Fungal Disease in Pediatric Solid Organ Transplant Recipients. AB - Background: Solid organ transplant (SOT) recipients are at risk for invasive fungal disease (IFD). Data on IFD burden in pediatric patients are limited. We aimed to determine the incidence and outcome of IFD in a large cohort of pediatric patients who underwent SOT. Methods: A single-center cohort of pediatric patients who underwent SOT between 2000 and 2013 was assembled retrospectively. The patients were followed for 180 days after transplant or until death to determine the presence or absence of IFD. The 2008 European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group Consensus Group criteria were used to define IFD as proven or probable. The incidence of IFD, all-cause mortality rate, and case-fatality rate at 180 days were calculated. Results: Among 584 pediatric patients who underwent SOT, 13 patients sustained 14 episodes of IFD (candidiasis, aspergillosis, and mucormycosis). The overall incidence was 2.2% (14.3 IFD events per 100000 patient days). The IFD rates according to transplant type were 12.5% (1 of 8) (heart/lung), 11.4% (4 of 35) (lung), 4.7% (8 of 172) (liver), 0% (0 of 234) (kidney), and 0% (0 of 135) (heart). Three patients with IFD (2 lung and 1 heart/lung) died, and all these deaths were deemed likely attributable to the IFD; the case-fatality rate was 21.4% (3 of 14). Conclusions: The overall incidence of IFD in these pediatric SOT recipients was low but varied across transplant type, with heart/lung and lung recipients having the highest IFD rate. Given the attributable case-fatality rate, the risk of death resulting from IFD is potentially high. More data on groups at higher risk, such as lung transplant recipients, are needed to guide targeted antifungal prophylaxis. PMID- 28992292 TI - MacroH2A1.1 cooperates with EZH2 to promote adipogenesis by regulating Wnt signaling. AB - White adipocytes play important roles in many physiological processes, including energy storage, endocrine signaling, and inflammatory responses. Understanding the molecular mechanisms of adipocyte formation (adipogenesis) provides insights into therapeutic approaches against obesity and its related diseases. Many transcriptional factors and epigenetic enzymes are known to regulate adipogenesis; however, whether histone variants play a role in this process is unknown. Here we found that macroH2A1.1 (mH2A1.1), a variant of histone H2A, was upregulated during adipocyte differentiation in 3T3-L1 cells and in the white adipose tissue of obese mice. Ablation of mH2A1.1 activated Wnt/beta-catenin signaling pathway, while overexpression of mH2A1.1 showed opposite effects. We further found that mH2A1.1 regulated Wnt/beta-catenin signaling pathway by cooperating with EZH2, a histone H3K27 methyltransferase, thus led to accumulation of H3K27me2 and H3K27me3 on the promoters of Wnt genes. Mutations in the macro-domain, mH2A1.1G224E, and mH2A1.1G314E, not only impaired adipogenesis, but also impaired the binding ability of mH2A1.1 to EZH2 and the enrichments of H3K27me2 and H3K27me3 on the promoters of Wnt genes. Together, our study reveals a novel regulatory role of mH2A1.1 in adipogenesis and obesity, which provides new insights in white fat development. PMID- 28992294 TI - New insights into stem cells. PMID- 28992291 TI - Retinoic acid inhibits white adipogenesis by disrupting GADD45A-mediated Zfp423 DNA demethylation. AB - Retinoic acid (RA), a bioactive metabolite of vitamin A, is a critical mediator of cell differentiation. RA blocks adipogenesis, but mechanisms remain to be established. ZFP423 is a key transcription factor maintaining white adipose identity. We found that RA inhibits Zfp423 expression and adipogenesis via blocking DNA demethylation in the promoter of Zfp423, a process mediated by growth arrest and DNA-damage-inducible protein alpha (GADD45A). RA induces the partnering between retinoic acid receptor (RAR) and tumor suppressor inhibitor of growth protein 1 (ING1), which prevents the formation of GADD45A and ING1 complex necessary for locus-specific Zfp423 DNA demethylation. In vivo, vitamin A supplementation prevents obesity, downregulates Gadd45a expression, and reduces GADD45A binding and DNA demethylation in the Zfp423 promoter. Inhibition of Zfp423 expression due to RA contributes to the enhanced brown adipogenesis. In summary, RA inhibits white adipogenesis by inducing RAR and ING1 interaction and inhibiting Gadd45a expression, which prevents GADD45A-mediated DNA demethylation. PMID- 28992293 TI - Inducible overexpression of RUNX1b/c in human embryonic stem cells blocks early hematopoiesis from mesoderm. AB - RUNX1 is absolutely required for definitive hematopoiesis, but the function of RUNX1b/c, two isoforms of human RUNX1, is unclear. We established inducible RUNX1b/c-overexpressing human embryonic stem cell (hESC) lines, in which RUNX1b/c overexpression prevented the emergence of CD34+ cells from early stage, thereby drastically reducing the production of hematopoietic stem/progenitor cells. Simultaneously, the expression of hematopoiesis-related factors was downregulated. However, such blockage effect disappeared from day 6 in hESC/AGM S3 cell co-cultures, proving that the blockage occurred before the generation of hemogenic endothelial cells. This blockage was partially rescued by RepSox, an inhibitor of the transforming growth factor (TGF)-beta signaling pathway, indicating a close relationship between RUNX1b/c and TGF-beta pathway. Our results suggest a unique inhibitory function of RUNX1b/c in the development of early hematopoiesis and may aid further understanding of its biological function in normal and diseased models. PMID- 28992295 TI - Phylogenetic Relationships, Breeding Implications, and Cultivation History of Hawaiian Taro (Colocasia Esculenta) Through Genome-Wide SNP Genotyping. AB - Taro, Colocasia esculenta, is one of the world's oldest root crops and is of particular economic and cultural significance in Hawai'i, where historically more than 150 different landraces were grown. We developed a genome-wide set of more than 2400 high-quality single nucleotide polymorphism (SNP) markers from 70 taro accessions of Hawaiian, South Pacific, Palauan, and mainland Asian origins, with several objectives: 1) uncover the phylogenetic relationships between Hawaiian and other Pacific landraces, 2) shed light on the history of taro cultivation in Hawai'i, and 3) develop a tool to discriminate among Hawaiian and other taros. We found that almost all existing Hawaiian landraces fall into 5 monophyletic groups that are largely consistent with the traditional Hawaiian classification based on morphological characters, for example, leaf shape and petiole color. Genetic diversity was low within these clades but considerably higher between them. Population structure analyses further indicated that the diversification of taro in Hawai'i most likely occurred by a combination of frequent somatic mutation and occasional hybridization. Unexpectedly, the South Pacific accessions were found nested within the clades mainly composed of Hawaiian accessions, rather than paraphyletic to them. This suggests that the origin of clades identified here preceded the colonization of Hawai'i and that early Polynesian settlers brought taro landraces from different clades with them. In the absence of a sequenced genome, this marker set provides a valuable resource towards obtaining a genetic linkage map and to study the genetic basis of phenotypic traits of interest to taro breeding such as disease resistance. PMID- 28992297 TI - Vacuolar degradation of chloroplast components: autophagy and beyond. AB - Chloroplast degradation during natural or stress-induced senescence requires the participation of both plastidic and extraplastidic degradative pathways. As part of the extraplastidic pathways, chloroplasts export stroma, envelope, and thylakoid proteins in membrane-bound organelles that are ultimately degraded in vacuoles. Some of these pathways, such as the formation of senescence-associated vacuoles (SAVs) and CV-containing vesicles (CCVs), do not depend on autophagy, whereas delivery of Rubisco-containing bodies (RCBs), ATI1-PS (ATG8-interacting Protein 1) bodies, and small starch-like granule (SSLG) bodies is autophagy dependent. In addition, autophagy of entire chloroplasts delivers damaged chloroplasts into the vacuolar lumen for degradation. This review summarizes the autophagy-dependent and independent trafficking mechanisms by which plant cells degrade chloroplast components in vacuoles. PMID- 28992296 TI - Efficacy and Safety of Sacubitril/Valsartan (LCZ696) Compared With Olmesartan in Elderly Asian Patients (>=65 Years) With Systolic Hypertension. AB - OBJECTIVE: Systolic hypertension is common in elderly patients and remains a challenge to treat effectively. The efficacy and safety of sacubitril/valsartan (LCZ696), a first-in-class angiotensin receptor neprilysin inhibitor, vs. olmesartan was evaluated in elderly Asian patients (>=65 years) with systolic hypertension. METHODS: In this randomized, double-blind, 14-week study, patients initially received once-daily sacubitril/valsartan 100 mg or olmesartan 10 mg, increased to sacubitril/valsartan 200 mg or olmesartan 20 mg at week 4. At week 10, for patients with blood pressure (BP) >140/90 mm Hg, the doses were up titrated to sacubitril/valsartan 400 mg or olmesartan 40 mg. The primary assessment was superiority of sacubitril/valsartan vs. olmesartan in reducing office mean sitting (ms) systolic BP (msSBP) from baseline at week 10. Secondary efficacy assessments included changes from baseline in ms diastolic BP (msDBP), ms pulse pressure (msPP), 24-hour mean ambulatory (ma) BP (maBP), and maPP at week 10; msBP and msPP at weeks 4 and 14. RESULTS: Overall, 588 patients were randomized (mean age, 70.7 years; baseline msBP, 160.3/84.9 mm Hg; msPP, 75.4 mm Hg). At week 10, sacubitril/valsartan provided superior msSBP reductions vs. olmesartan (22.71 vs. 16.11 mm Hg, respectively; P < 0.001); similarly, reductions from baseline in other BP and PP assessments were significantly greater with sacubitril/valsartan. At week 14, despite more patients requiring up titration in the olmesartan group, msBP and msPP reductions from baseline were significantly greater with sacubitril/valsartan. Both treatments were generally well-tolerated. CONCLUSION: Sacubitril/valsartan is more effective than olmesartan in reducing BP in elderly Asian patients with systolic hypertension. PMID- 28992298 TI - Incidence of Pneumocystis jirovecii and Adverse Events Associated With Pneumocystis Prophylaxis in Children Receiving Glucocorticoids. AB - Background: Antimicrobial prophylaxis is indicated to prevent Pneumocystis jirovecii pneumonia (PJP) in profoundly immunosuppressed children. The incidence of PJP infection in children with chronic glucocorticoid exposure is unknown, and PJP prophylaxis has been associated with adverse events. We hypothesized that PJP infection is rare in children without human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), cancer, or a transplant history who are using chronic glucocorticoids and that those exposed to PJP prophylaxis are more likely to experience a cutaneous hypersensitivity reaction or myelosuppression than unexposed patients. Methods: This study involved a retrospective cohort from the Clinformatics Data Mart Database (OptumInsight, Eden Prairie, MN). We identified patients <=18 years of age who received at least 2 prescriptions for a systemic glucocorticoid within a 60-day period and excluded patients with a history of PJP infection, an oncologic diagnosis, transplant, or HIV/AIDS. PJP prophylaxis exposure was identified by using national drug codes. Cutaneous hypersensitivity reaction or myelosuppression was identified by using International Classification of Diseases, 9th Revision (ICD-9), codes. We used a discrete time-failure model to examine the association between exposure and outcome. Results: We identified 119399 children on glucocorticoids, 10% of whom received PJP prophylaxis. The incidences of PJP were 0.61 and 0.53 per 10000 patient-years in children exposed and those unexposed to PJP prophylaxis, respectively. In a multivariable model, trimethoprim-sulfamethoxazole was associated with cutaneous hypersensitivity reaction (odds ratio, 3.20; 95% confidence interval, 2.62-3.92) and myelosuppression (odds ratio, 1.85; 95% confidence interval, 1.56-2.20). Conclusions: PJP infection was rare in children using glucocorticoids chronically, and PJP prophylaxis-associated cutaneous hypersensitivity reactions and myelosuppression are more common. The use of PJP chemoprophylaxis in children without HIV/AIDS, cancer, or a transplant history who are taking glucocorticoids chronically should be considered carefully. PMID- 28992299 TI - Fracture after radiation therapy for femoral metastasis: incidence, timing and clinical features. AB - We analyzed 428 femoral metastases initially treated with radiotherapy between 2002 and 2011 to clarify the clinical details of post-irradiation fractures of femoral metastasis. Patients included 161 men and 167 women, with a mean age of 62 years. Fracture incidence, fracture site, fracture risk based on X-ray images before radiotherapy, and interval from completion of radiotherapy to fracture occurrence were assessed. In addition, 24 pathological specimens obtained during 27 surgeries for these fractures were examined. Fractures occurred in 7.7% of 428 femoral metastases (total 33: 28 actual fractures and five virtual fractures with progressive pain and bone destruction). The fracture rate was 7.8% in the proximal femur and 1.5% in the shaft (P = 0.001). Fractures occurred a median of 4.4 months after radiotherapy, with 39.4% occurring within 3 months and 63.6% within 6 months. Among femurs with high fracture risk according to Harrington's criteria or Mirels' score, the fracture rate was 13.9% and 11.8%, respectively. Viable tumor cells were detected in all five patients with painful virtual fracture, in 85.7% of femurs with actual fractures that occurred within 3 months, and in only 25.0% of actual fractures occurring after 3 months. Post-irradiation fractures of femoral metastasis most frequently occurred within 3 months after radiotherapy, and were more common in the peritrochanteric area than in the shaft. Radiological evidence of impending fracture did not correlate with a high fracture rate. Actual fractures occurring after more than 3 months were likely caused by post-irradiation fragility of the femur, without viable tumor cells. PMID- 28992300 TI - COP1 regulates plant growth and development in response to light at the post translational level. AB - Photoreceptors perceive different wavelengths of light and transduce light signals downstream via a range of proteins. COP1, an E3 ubiquitin ligase, regulates light signaling by mediating the ubiquitination and subsequent proteasomal degradation of photoreceptors such as phytochromes and cryptochromes, as well as various development-related proteins including other light-responsive proteins. COP1 is itself regulated by direct interactions with several signaling molecules that modulate its activity. The control of photomorphogenesis by COP1 is also regulated by its localization to the cytoplasm in response to light. COP1 thus acts as a tightly regulated switch that determines whether development is skotomorphogenic or photomorphogenic. In this review, we discuss the effects of COP1 on the abundance and activity of various development-related proteins, including photoreceptors, and summarize the regulatory mechanisms that influence COP1 activity and stability in plants. PMID- 28992301 TI - Sensory Biology of Starfish-With Emphasis on Recent Discoveries in their Visual Ecology. AB - Asteroidea, starfish, constitutes a major part of the macrobenthos in most marine environments. Being members of the echinoderms, they have a nervous system with no well-defined central nervous system. Accordingly, starfish are assumed to pick up rather limited information from the surroundings, and it is also often assumed that most of their behaviors are guided by olfaction. Here, the sensory biology of starfish is reviewed in order to evaluate these assumptions. There is a vast amount of behavioral data dealing with mechanoreception, chemoreception, and combinations of the two (chemosensory-mediated rheotaxis), but the receptors have not yet been identified and almost nothing is known about the physiology behind these senses. What can be concluded from the available data is that starfish possess a sense of touch, some are able to sense gravity and many display positive rheotaxis, moving up currents. A number of starfish species use olfaction during foraging and prey localization. Interestingly, eyes are also present in most starfish, and recent studies have documented that in Linckia laevigata and Acanthaster planci vision plays a major role in seeking out their feeding grounds. The physiology and structure of the eyes filter out small moving objects while optimizing the contrast between the large stationary objects (e.g., coral boulders in the habitat) and the surrounding water. These new results demonstrate the importance of controlling the visual environment when conducting experiments on starfish behavior. PMID- 28992303 TI - Dominant Allele Phylogeny and Constitutive Subgenome Haplotype Inference in Bananas Using Mitochondrial and Nuclear Markers. AB - Cultivated bananas (Musa spp.) have undergone domestication patterns involving crosses of wild progenitors followed by long periods of clonal propagation. Majority of cultivated bananas are polyploids with different constitutive subgenomes and knowledge on phylogenies to their progenitors at the species and subspecies levels is essential. Here, the mitochondrial (NAD1) and nuclear (CENH3) markers were used to phylogenetically position cultivated banana genotypes to diploid progenitors. The CENH3 nuclear marker was used to identify a minimum representative haplotype number in polyploids and diploid bananas based on single nucleotide polymorphisms. The mitochondrial marker NAD1 was observed to be ideal in differentiating bananas of different genomic constitutions based on size of amplicons as well as sequence. The genotypes phylogenetically segregated based on the dominant genome; AAB genotypes grouped with AA and AAA, and the ABB together with BB. Both markers differentiated banana sections, but could not differentiate subspecies within the A genomic group. On the basis of CENH3 marker, a total of 13 haplotypes (five in both diploid and triploid, three in diploids, and rest unique to triploids) were identified from the genotypes tested. The presence of haplotypes, which were common in diploids and triploids, stipulate possibility of a shared ancestry in the genotypes involved in this study. Furthermore, the presence of multiple haplotypes in some diploid bananas indicates their being heterozygous. The haplotypes identified in this study are of importance because they can be used to check the level of homozygozity in breeding lines as well as to track segregation in progenies. PMID- 28992302 TI - Northern Spotted Owl (Strix occidentalis caurina) Genome: Divergence with the Barred Owl (Strix varia) and Characterization of Light-Associated Genes. AB - We report here the assembly of a northern spotted owl (Strix occidentalis caurina) genome. We generated Illumina paired-end sequence data at 90* coverage using nine libraries with insert lengths ranging from ~250 to 9,600 nt and read lengths from 100 to 375 nt. The genome assembly is comprised of 8,108 scaffolds totaling 1.26 * 109 nt in length with an N50 length of 3.98 * 106 nt. We calculated the genome-wide fixation index (FST) of S. o. caurina with the closely related barred owl (Strix varia) as 0.819. We examined 19 genes that encode proteins with light-dependent functions in our genome assembly as well as in that of the barn owl (Tyto alba). We present genomic evidence for loss of three of these in S. o. caurina and four in T. alba. We suggest that most light-associated gene functions have been maintained in owls and their loss has not proceeded to the same extent as in other dim-light-adapted vertebrates. PMID- 28992304 TI - Pherotype Polymorphism in Streptococcus pneumoniae Has No Obvious Effects on Population Structure and Recombination. AB - Natural transformation in the Gram-positive pathogen Streptococcus pneumoniae occurs when cells become "competent," a state that is induced in response to high extracellular concentrations of a secreted peptide signal called competence stimulating peptide (CSP) encoded by the comC locus. Two main CSP signal types (pherotypes) are known to dominate the pherotype diversity across strains. Using 4,089 fully sequenced pneumococcal genomes, we confirm that pneumococcal populations are highly genetically structured and that there is significant variation among diverged populations in pherotype frequencies; most carry only a single pherotype. Moreover, we find that the relative frequencies of the two dominant pherotypes significantly vary within a small range across geographical sites. It has been variously proposed that pherotypes either promote genetic exchange among cells expressing the same pherotype, or conversely that they promote recombination between strains bearing different pherotypes. We attempt to distinguish these hypotheses using a bioinformatics approach by estimating recombination frequencies within and between pherotypes across 4,089 full genomes. Despite underlying population structure, we observe extensive recombination between populations; additionally, we found significantly higher (although marginal) rates of genetic exchange between strains expressing different pherotypes than among isolates carrying the same pherotype. Our results indicate that pherotypes do not restrict, and may even slightly facilitate, recombination between strains; however, these marginal effects suggest the more likely possibility that the cause of CSP polymorphism lies outside of its effects on transformation. Our results suggest that the CSP balanced polymorphism does not causally underlie population differentiation. Therefore, when strains carrying different pherotypes encounter one another during cocolonization, genetic exchange can occur without restriction. PMID- 28992305 TI - Persulfidation proteome reveals the regulation of protein function by hydrogen sulfide in diverse biological processes in Arabidopsis. AB - Hydrogen sulfide-mediated signaling pathways regulate many physiological and pathophysiological processes in mammalian and plant systems. The molecular mechanism by which hydrogen sulfide exerts its action involves the post translational modification of cysteine residues to form a persulfidated thiol motif, a process called protein persulfidation. We have developed a comparative and quantitative proteomic analysis approach for the detection of endogenous persulfidated proteins in wild-type Arabidopsis and L-CYSTEINE DESULFHYDRASE 1 mutant leaves using the tag-switch method. The 2015 identified persulfidated proteins were isolated from plants grown under controlled conditions, and therefore, at least 5% of the entire Arabidopsis proteome may undergo persulfidation under baseline conditions. Bioinformatic analysis revealed that persulfidated cysteines participate in a wide range of biological functions, regulating important processes such as carbon metabolism, plant responses to abiotic and biotic stresses, plant growth and development, and RNA translation. Quantitative analysis in both genetic backgrounds reveals that protein persulfidation is mainly involved in primary metabolic pathways such as the tricarboxylic acid cycle, glycolysis, and the Calvin cycle, suggesting that this protein modification is a new regulatory component in these pathways. PMID- 28992307 TI - Attempted molecular detection of the thermally dimorphic human fungal pathogen Emergomyces africanus in terrestrial small mammals in South Africa. AB - The ecological niche of Emergomyces africanus (formerly Emmonsia species), a dimorphic fungus that causes an AIDS-related mycosis in South Africa, is unknown. We hypothesized that natural infection with E. africanus occurs in wild small mammals. Using molecular detection with primers specific for E. africanus, we examined 1402 DNA samples from 26 species of mole-rats, rodents, and insectivores trapped in South Africa that included 1324 lung, 37 kidney, and 41 liver specimens. DNA of E. africanus was not detected in any animals. We conclude that natural infection of wild small mammals in South Africa with E. africanus has not been proven. PMID- 28992306 TI - Delaying chloroplast turnover increases water-deficit stress tolerance through the enhancement of nitrogen assimilation in rice. AB - Abiotic stress-induced senescence in crops is a process particularly affecting the photosynthetic apparatus, decreasing photosynthetic activity and inducing chloroplast degradation. A pathway for stress-induced chloroplast degradation that involves the CHLOROPLAST VESICULATION (CV) gene was characterized in rice (Oryza sativa) plants. OsCV expression was up-regulated with the age of the plants and when plants were exposed to water-deficit conditions. The down regulation of OsCV expression contributed to the maintenance of the chloroplast integrity under stress. OsCV-silenced plants displayed enhanced source fitness (i.e. carbon and nitrogen assimilation) and photorespiration, leading to water deficit stress tolerance. Co-immunoprecipitation, intracellular co-localization, and bimolecular fluorescence demonstrated the in vivo interaction between OsCV and chloroplastic glutamine synthetase (OsGS2), affecting source-sink relationships of the plants under stress. Our results would indicate that the OsCV-mediated chloroplast degradation pathway is involved in the regulation of nitrogen assimilation during stress-induced plant senescence. PMID- 28992308 TI - Relationship between intracranial pressure and antifungal agents levels in the CSF of patients with cryptococcal meningitis. AB - The purpose of this study was to evaluate the influence of intracranial hypertension in the cerebrospinal fluid (CSF) levels of amphotericin B and fluconazole levels of patients with cryptococcal meningitis. CSF samples and intracranial pressure were obtained by means of routine punctures performed at days 1, 7, and 14 of therapy, respectively. Amphotericin B and fluconazole CSF levels were measured by HPLC method as previously described. The minimum inhibitory concentration for amphotericin B, fluconazole, 5?flucytosine, and voriconazole of each Cryptococcus isolate was performed according to CLSI. The predominant Cryptococcus species found was C. neoformans, and the major underlying condition was AIDS. Only one CSF sample had a detectable level for amphotericin B during the 14 days of therapy. Fluconazole CSF levels progressively increased from day 1 to day 14 of therapy for most cases. Fluconazole levels in the CSF were above the minimum inhibitory concentrations (MICs) for Cryptococcus during the initial 14 days of antifungal therapy. Variations of intracranial pressure did not affect amphotericin B and fluconazole levels in the CSF. The generalized estimating correlation (GEE) and Spearman correlation test (SCT) showed no significant correlation between the amphotericin B or fluconazole concentrations in the CSF and intracranial pressure (P = .953 and P = .093, respectively for GEE test and P = .477 and P = .847, respectively, for SCT). Combination therapy of amphotericin B with fluconazole was effective in 60% of the patients considering CSF cultures were negative in 9 of 15 patients after 14 days of therapy. Further studies are necessary to evaluate the role of intracranial hypertension on the therapeutic efficacy of different antifungal agents in patients with cryptococcal meningitis. PMID- 28992310 TI - Genetic Costs of Domestication and Improvement. AB - The "cost of domestication" hypothesis posits that the process of domesticating wild species can result in an increase in the number, frequency, and/or proportion of deleterious genetic variants that are fixed or segregating in the genomes of domesticated species. This cost may limit the efficacy of selection and thus reduce genetic gains in breeding programs for these species. Understanding when and how deleterious mutations accumulate can also provide insight into fundamental questions about the interplay of demography and selection. Here we describe the evolutionary processes that may contribute to deleterious variation accrued during domestication and improvement, and review the available evidence for "the cost of domestication" in animal and plant genomes. We identify gaps and explore opportunities in this emerging field, and finally offer suggestions for researchers and breeders interested in understanding or avoiding the consequences of an increased number or frequency of deleterious variants in domesticated species. PMID- 28992309 TI - A genome-wide survey with different rapeseed ecotypes uncovers footprints of domestication and breeding. AB - Rapeseed (Brassica napus L.) is an important oilseed crop. Despite a short period of domestication and breeding, rapeseed has formed three diverse ecotype groups, namely spring, winter, and semi-winter. However, the genetic changes among the three ecotype groups have remained largely unknown. To detect selective signals, a set of 327 accessions from a worldwide collection were genotyped using a Brassica array, producing 33 186 high-quality single nucleotide polymorphisms (SNPs). Linkage disequilibrium (LD) was unevenly distributed across the genome. A total of 705 (78.2%) weak LD regions were found in the A subgenome, whereas 445 (72.6%) strong LD regions were in the C subgenome. By calculating the nucleotide diversity and population differentiation indices, a total of 198 selective sweeps were identified across ecotype groups, spanning 5.91% (37.9 Mb) of the genome. Within these genome regions, a few known functional genes or loci were found to be in association with environmental adaptability and yield-related traits. In particular, all 12 SNPs detected in significant association with flowering time among accessions were in the selection regions between ecotype groups. These findings provide new insights into the structure of the B. napus genome and uncover the footprints of domestication and breeding. PMID- 28992311 TI - Pairing Increases Activation of V1aR, but not OTR, in Auditory Regions of Zebra Finches: The Importance of Signal Modality in Nonapeptide-Social Behavior Relationships. AB - Social relationships are complex, involving the production and comprehension of signals, individual recognition, and close coordination of behavior between two or more individuals. The nonapeptides oxytocin and vasopressin are widely believed to regulate social relationships. These findings come largely from prairie voles, in which nonapeptide receptors in olfactory neural circuits drive pair bonding. This research is assumed to apply to all species. Previous reviews have offered two competing hypotheses. The work of Sarah Newman has implicated a common neural network across species, the Social Behavior Network. In contrast, others have suggested that there are signal modality-specific networks that regulate social behavior. Our research focuses on evaluating these two competing hypotheses in the zebra finch, a species that relies heavily on vocal/auditory signals for communication, specifically the neural circuits underlying singing in males and song perception in females. We have demonstrated that the quality of vocal interactions is highly important for the formation of long-term monogamous bonds in zebra finches. Qualitative evidence at first suggests that nonapeptide receptor distributions are very different between monogamous rodents (olfactory species) and monogamous birds (vocal/auditory species). However, we have demonstrated that social bonding behaviors are not only correlated with activation of nonapeptide receptors in vocal and auditory circuits, but also involve regions of the common Social Behavior Network. Here, we show increased Vasopressin 1a receptor, but not oxytocin receptor, activation in two auditory regions following formation of a pair bond. To our knowledge, this is the first study to suggest a role of nonapeptides in the auditory circuit in pair bonding. Thus, we highlight converging mechanisms of social relationships and also point to the importance of studying multiple species to understand mechanisms of behavior. PMID- 28992312 TI - Long-chain fatty acids inhibit human members of the aldo-keto reductase 1C subfamily. AB - Four human hydroxysteroid dehydrogenases in the aldo-keto reductase (AKR) superfamily, AKR1C1-AKR1C4, are involved in the metabolism of steroids and other carbonyl compounds including drugs, and altered expression of AKRs (1C1, 1C2 and/or 1C3) is related to the pathogenesis of several extrahepatic cancers. Here, we report that unsaturated fatty acids (FAs) are potent competitive inhibitors of the AKR enzymes. The sensitivities to the FAs were different among the enzymes, especially between AKR1C1 and AKR1C2. The most potent inhibitors for AKR1C1, AKR1C2 and AKR1C4 were docosahexaenoic acid (Ki 0.77 uM), palmitoleic acid (Ki 0.41 uM) and linoleic acid (Ki 0.33 uM), respectively. AKR1C3 was the most sensitive to FA inhibition, showing low Ki values (0.23-0.29 uM) for oleic, linoleic, eicosapentaenoic and docosahexaenoic acids. Linoleic and oleic acids also inhibited AKR1C3-mediated metabolism of 9,10-phenanthrenequinone in colon DLD1 cells. Molecular docking and site-directed mutagenesis studies suggested upon FA binding to AKR1C1 and AKR1C3: (i) the carboxyl group of the FA binds to the oxyanion-binding site in the active site; (ii) the difference in FA sensitivity between AKR1C1 and AKR1C2 is due to their residue difference at position 54; (iii) Ser118, Phe306 and Phe311 of AKR1C3 are important for determining the inhibitory potency of FAs. PMID- 28992313 TI - Secular trends in the incidence of end-stage renal disease and its risk factors in Japanese patients with immunoglobulin A nephropathy. AB - Background: There are limited data on secular trends in the incidence of end stage renal disease (ESRD) and frequencies of its risk factors or treatment modalities in patients with immunoglobulin A nephropathy (IgAN). Methods: This study divided 1255 patients with IgAN into three groups according to the timing of renal biopsy: 1979-89 (n = 232), 1990-99 (n = 574) and 2000-10 (n = 449). The age-adjusted incidence rates, incidence rate ratios and 95% confidence intervals (CIs) for ESRD were calculated by the person-year method and compared using Poisson regression analysis. Results: A total of 63 patients (5.0%) developed ESRD. The age-adjusted incidence of ESRD decreased significantly over time, i.e. 11.5 per 1000 person-years (95% CI 5.4-24.6) in 1979-89, 6.5 per 1000 person years (95% CI 1.0-25.2) in 1990-99 and 4.2 per 1000 person-years (95% CI 1.0 17.7) in 2000-10. The proportions of patients with preserved renal function and acute-stage inflammatory histologic changes (i.e. endocapillary hypercellularity and extracapillary proliferation) at the timing of biopsy increased over time, as did the rates of prescriptions of renin-angiotensin system blockers and corticosteroids (all P for trend <0.05). The effect of acute inflammatory histologic lesions on renal prognosis was drastically reduced over time. Conclusions: These findings suggest that early diagnosis in the acute inflammatory phase and subsequent aggressive treatment may have contributed to the significant downward trend in the incidence of ESRD in patients with IgAN over three decades. PMID- 28992314 TI - Nutritional therapy reduces protein carbamylation through urea lowering in chronic kidney disease. AB - Background: Protein carbamylation is one of the non-enzymatic reactions involved in protein molecular ageing. We sought to investigate the relationship between urea levels and protein carbamylation, and whether a Mediterranean diet (MD) and a very low protein diet (VLPD) reduce protein carbamylation through reduction in urea levels in patients with chronic kidney disease (CKD). Methods: This is a prospective, randomized, crossover controlled trial that investigated 60 patients with CKD grades 3B-4 (46 males, mean age of 67 years). The enrolled CKD patients were randomly assigned (1:1) to two different nutritional treatment arms: (i) 3 months of free diet (FD), 6 months of VLPD, 3 months of FD and 6 months of MD; and (ii) 3 months of FD, 6 months of MD, 3 months of FD and 6 months of VLPD. Blood levels of lysine (Lys) and homocitrulline (Hcit) and their ratio were used as markers of cyanate levels. Due to a lack of pre-existing data on the potential effects of different dietary regimens and in light of the exploratory nature of the study, no formal sample size estimation was carried out. Results: At study completion, lower diastolic blood pressure and decreased serum levels of urea, sodium, phosphorus and parathyroid hormone, but higher serum levels of bicarbonate and haemoglobin, were noted with MD and VLPD. When compared with FD, both MD and VLPD were also associated with a decrease in serum Hcit levels and Hcit/Lys ratios (P < 0.001). Notably, reductions in urea levels correlated with substantial reductions in Hcit levels (R2 = 0.16 and 0.17 for VLPD and MD, respectively). Conclusion: In conclusion, nutritional treatments that significantly decrease serum levels of urea are associated with reduced protein carbamylation. PMID- 28992315 TI - Amphotericin B and terbinafine but not the azoles prolong survival in Galleria mellonella larvae infected with Madurella mycetomatis. AB - Mycetoma is a tropical neglected disease characterized by large subcutaneous lesions in which the causative organisms reside in the form of grains. The most common causative agent is Madurella mycetomatis. Antifungal therapy often fails due to these grains, but to identify novel treatment options has been difficult since grains do not form in vitro. We recently used Galleria mellonella larvae to develop an in vivo grain model. In the current study, we set out to determine the therapeutic efficacy of commonly used antifungal agents in this larval model. Pharmacokinetics of ketoconazole, itraconazole, voriconazole, posaconazole, amphotericin B, and terbinafine were determined in the hemolymph of G. mellonella larvae. Antifungal therapy was given either therapeutically or prophylactic on three consecutive days in therapeutically equivalent dosages. Survival was monitored for 10 days and colony-forming units (cfu) and melanization were determined on day 3. Measurable concentrations of antifungal agents were found in the hemolymph of the larvae. None of the azole antifungal agents prolonged survival when given therapeutically or prophylactically. Amphotericin B and terbinafine did prolong survival, even at concentrations below the minimal inhibitory concentration of M. mycetomatis. The cfu and melanization did not differ between any of the treated groups and phosphate-buffered saline (PBS) treated groups. Grains were still present in surviving larvae but appeared to be encapsulated. This study demonstrated for the first time a comparison between the efficacy of different antifungal agents toward grains of M. mycetomatis. It appeared that amphotericin B and terbinafine were able to prolong larval survival. PMID- 28992316 TI - Phosphorylation of CBX2 controls its nucleosome-binding specificity. AB - Chromobox 2 (CBX2), a component of polycomb repressive complex 1 (PRC1), binds lysine 27-methylated histone H3 (H3K27me3) via its chromodomain (CD) and plays a critical role in repressing developmentally regulated genes. The phosphorylation of CBX2 has been described in several studies, but the biological implications of this modification remain largely elusive. Here, we show that CBX2's phosphorylation plays an important role in its nucleosome binding. CBX2 is stably phosphorylated in vivo, and domain analysis showed that residues in CBX2's serine rich (SR) region are the predominant phosphorylation sites. The serine residues in an SR region followed by an acidic-residue (AR) cluster coincide with the consensus target of casein kinase II (CK2), and CK2 efficiently phosphorylated the SR region in vitro. A nucleosome pull-down assay revealed that CK2 phosphorylated CBX2 had a high specificity for H3K27me3-modified nucleosomes. An electrophoretic mobility-shift assay showed that CK2-mediated phosphorylation diminished CBX2's AT-hook-associated DNA-binding activity. Mutant CBX2 lacking the SR region or its neighboring AR cluster failed to repress the transcription of p21, a gene targeted by PRC1. These results suggest that CBX2's phosphorylation is critical for its transcriptional repression of target genes. PMID- 28992317 TI - Mycoplasma hominis Empyema in an 18-Year-old Stem Cell and Lung Transplant Recipient: Case Report and Review of the Literature. AB - Mycoplasma hominis has been identified as a rare cause of respiratory infections in immunocompromised adults. Here, we describe a case of Mycoplasma hominis empyema in an 18-year-old immunocompromised patient with a review of the literature highlighting diagnostic challenges associated with this infection. PMID- 28992318 TI - The deubiquitinase UCHL5/UCH37 positively regulates Hedgehog signaling by deubiquitinating Smoothened. AB - The Hedgehog (Hh) signaling pathway plays important roles in developmental processes including pattern formation and tissue homeostasis. The seven-pass transmembrane receptor Smoothened (Smo) is the pivotal transducer in the pathway; it, and thus the pathway overall, is regulated by ubiquitin-mediated degradation, which occurs in the absence of Hh. In the presence of Hh, the ubiquitination levels of Smo are decreased, but the molecular basis for this outcome is not well understood. Here, we identify the deubiquitinase UCHL5 as a positive regulator of the Hh pathway. We provide both genetic and biochemical evidence that UCHL5 interacts with and deubiquitinates Smo, increasing stability and promoting accumulation at the cell membrane. Strikingly, we find that Hh enhances the interaction between UCHL5 and Smo, thereby stabilizing Smo. We also find that proteasome subunit RPN13, an activator of UCHL5, could enhance the effect of UCHL5 on Smo protein level. More importantly, we find that the mammalian counterpart of UCHL5, UCH37, plays the same role in the regulation of Hh signaling by modulating hSmo ubiquitination and stability. Our findings thus identify UCHL5/UCH37 as a critical regulator of Hh signaling and potential therapeutic target for cancers. PMID- 28992319 TI - Atrial fibrillation in kidney transplant recipients: is there a place for the novel drugs? AB - Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia of high clinical importance, occurring in 2% of the general population and in 19-24% in patients with chronic kidney disease. It is a well-known risk factor for cardiovascular morbidity and mortality. Kidney transplant recipients with a history of AF were associated with significantly higher rate of ischaemic strokes, graft failure and post-transplant mortality. AF occurs in over 7% of kidney transplant recipients in the first 3 years after transplantation and is associated with reduced graft and patient survival. The incidence of stroke in patients after kidney transplantation (KTx) is higher than the general population, but markedly lower than those on dialysis. Oral anticoagulation (OAC) therapy is recommended in AF patients at high risk of stroke. There are no randomized studies assessing OAC in patients after KTx and there are no specific recommendations and guidelines on therapeutic strategies in these patients. KTx recipients are a vulnerable population, exposed to variations in renal function, being at higher risk of bleeding and thrombotic complications, with possible interactions with immunosuppression. Surely, there is a place for novel oral anticoagulants (NOACs) in this group of patients as long as the summary of product characteristics is followed, as they are a valuable anticoagulation therapy. On one hand, they are at least as effective as warfarin; on the other hand NOACs are safer, especially when it comes to intracranial haemorrhages. However, NOACs seem to be underused in this population as they are excreted via kidney, may interact with immunosuppressive therapy and physicians need more experience and confidence in their administration. Percutaneous left atrial appendage occlusion procedure may also be considered as an opportunity for this group of patients, in particular in the presence of contraindications to anticoagulation. PMID- 28992321 TI - Pregnancy-associated plasma protein-A predicts survival in end-stage renal disease-confounding and modifying effects of cardiovascular disease, body composition and inflammation. AB - Background: High pregnancy-associated plasma protein-A (PAPP-A) levels are linked to atherosclerosis and associate with increased mortality in prevalent dialysis patients. We investigated associations of PAPP-A, measured at dialysis initiation, with cardiovascular disease (CVD), CVD risk factors and mortality in incident dialysis patients, and explored if body composition and inflammation modulated these associations. Methods: Baseline plasma PAPP-A levels, inflammation biomarkers and body composition, using dual-energy X-ray absorptiometry, were measured in 286 incident dialysis patients. Primary outcome was survival during 60 months follow-up. Quantile (median) regression was used for cross-sectional analysis and Kaplan-Meier diagrams and Cox proportional hazards regression for survival analysis. Results: In cross-sectional analysis adjusted for age and sex, PAPP-A levels were associated with lean tissue index (LTI) and high-sensitivity C-reactive protein (hsCRP) but not with fat tissue index (FTI) or history of CVD. In a model also including diabetes mellitus (DM), the association with LTI did not remain statistically significant. When adjusted for cardiovascular risk factors and body composition, higher PAPP-A levels showed a moderate but significant association [hazard ratio (HR) = 1.2, 95% confidence interval (CI): 1-1.4, P = 0.04] with mortality. When also including hsCRP the association was attenuated (HR = 1.2, 95% CI: 0.99-1.4, P = 0.06). In survival analysis, interactions with PAPP-A on the multiplicative scale were found for hsCRP (HR = 1.6, 95% CI: 1.2-2.2, P = 0.004) and DM (HR = 1.6, 95% CI: 1.1-2.2, P = 0.01) and with DM and FTI on the additive scale. Conclusions: Higher PAPP-A levels are associated with worse survival in incident dialysis patients following adjustment for established cardiovascular risk factors and body composition indices, but not clearly so when adjusted for hsCRP. Inflammation, body composition (FTI) and DM were found to be potential effect modifiers for the observed moderate association of PAPP-A with survival. PMID- 28992320 TI - Effect of human leukocyte antigen mismatching on the outcomes of pediatric kidney transplantation: a systematic review and meta-analysis. AB - Background: Kidney transplantation is regarded as the optimal treatment for pediatric patients with end-stage renal disease. Here, we address a controversial topic in pediatric kidney transplantation by performing a quantitative evaluation of the effect of human leukocyte antigen (HLA) mismatching on the outcomes of pediatric kidney transplantation. Methods: We systematically searched PubMed, EMBASE and the Cochrane Library from their inception to 31 December 2016 for cohort studies assessing the risk ratio (RR) of HLA mismatching on pediatric kidney transplantation. Outcome measures included graft failure, rejection and all-cause mortality. RRs and 95% confidence intervals (CIs) were used as estimates of effect size in random-effect models. Results: Eighteen studies comprising a total of 26 018 pediatric recipients were included in the evaluation. Compared with 0-1 HLA-DR mismatch, 2 mismatches significantly increased the risk of graft failure at 1 year (RR: 1.41, 95% CI: 1.11-1.80), 3 years (RR: 1.28, 95% CI: 1.08-1.52), 5 years (RR: 1.21, 95% CI: 1.04-1.41) and 10 years (RR: 1.30, 95% CI: 1.02-1.67). For HLA-A + B, the 5-year graft failure risk was higher for 2-4 mismatches compared with 0-1 mismatch (RR: 3.17, 95% CI: 1.20 8.36), but not for 3-4 compared with 0-2 mismatches (RR: 1.49, 95% CI: 0.79 2.80). Conclusions: Based on pooled analysis, HLA-DR and HLA-A + B are important factors affecting post-transplant outcomes, especially graft failure, in pediatric recipients. Additional randomized controlled trials with higher quality evidence are needed for further investigation. PMID- 28992323 TI - Stress-induced senescence and plant tolerance to abiotic stress. AB - Senescence is an age-dependent process, ultimately leading to plant death, that in annual crop plants overlaps with the reproductive stage of development. Research on the molecular and biochemical mechanisms of leaf senescence has revealed a multi-layered regulatory network operating to control age-dependent processes. Abiotic stress-induced senescence challenges source-sink relationships and results in significant reduction in crop yields. Although processes associated with plant senescence are well studied, the mechanisms regulating stress-induced senescence are not well known. Here, we discuss the effects of abiotic stress on crop productivity, mechanisms associated with stress-induced senescence, and the possible use of these mechanisms for the generation of plant stress tolerance. We emphasize the involvement of source strength and stability of the photosynthetic apparatus in this process, and suggest a possible role of a perennial plant life strategy for the amelioration of stress-induced senescence. PMID- 28992324 TI - Zbed3 participates in the subcortical maternal complex and regulates the distribution of organelles. AB - We previously identified a subcortical maternal complex (SCMC) that is essential for early embryogenesis and female fertility in mice. However, the molecular mechanism by which the SCMC affects female fertility remains largely uncharacterized. Here, we report that a novel maternal protein, zinc finger BED type containing 3 (Zbed3), participates in the SCMC. Depletion of maternal Zbed3 results in reduced fecundity of females, because of the impaired and delayed development in a proportion of mutant embryos. The loss of maternal Zbed3 results in asymmetric zygotic division and abnormal distributions of organelles in the affected oocytes and zygotes, similar to the phenotypes observed in females with disrupted core SCMC genes. Further investigation revealed that these phenotypes are associated with disrupted dynamics of microtubules and/or formation of cytoplasmic lattices (CPLs). The stability and localization of Zbed3 depend on, but are not required for, the formation of the SCMC. Thus, our data suggest Zbed3 as one of downstream proteins mediating SCMC functions and provide further insights into the roles of the SCMC and CPLs in female fertility. PMID- 28992322 TI - Human Cytosolic Sulphotransferase SULT1C3: genomic analysis and functional characterization of splice variant SULT1C3a and SULT1C3d. AB - The cytosolic sulphotransferase SULT1C3 remained the most poorly understood human SULT. The SULT1C3 gene has been shown to contain alternative exons 7 and 8, raising the question concerning their evolutionary origin and implying the generation of multiple SULT1C3 variants. Two SULT1C3 splice variants, SULT1C3a and SULT1C3d, were investigated to verify the impact of alternative C-terminal sequences on their sulphating activity. Sequence homology and gene location analyses were performed to verify the orthology of the SULT1C3 gene. The SULT1C3 gene appears to be present only in humans and other primates, but alternative exons 7b and 8b share high degrees of homology with corresponding regions of rodent SULT1C1 genes, implying their evolutionary origin being from a defunct human SULT1C1 gene. Purified recombinant SULT1C3a and SULT1C3d were analyzed for sulphating activities toward a variety of endogenous and xenobiotic compounds. While SULT1C3a displayed weaker activities and strict substrate specificity toward hydroxyl-chlorinated biphenyls, SULT1C3d exhibited broader substrate specificity toward bile acids and thyroid hormones as well as hydroxyl chlorinated biphenyls. Molecular docking simulation suggested that Tyr249 and Met257 may play an important role in substrate recognition by SULT1C3d. Alternative splicing of exons 7 and 8 sequences resulted in differential catalytic properties of SULT1C3 variants. PMID- 28992325 TI - Congenital Babesiosis After Maternal Infection With Borrelia burgdorferi and Babesia microti. AB - We describe the cases of 2 infants with congenital babesiosis born to mothers with prepartum Lyme disease and subclinical Babesia microti infection. The infants both developed anemia, neutropenia, and thrombocytopenia, and 1 infant required red blood cell transfusion. Both infants recovered with treatment. Additional studies are warranted to define the optimal management strategy for pregnant women with early Lyme disease in geographic areas in which B microti infection is endemic. PMID- 28992327 TI - The steady-state level of CDK4 protein is regulated by antagonistic actions between PAQR4 and SKP2 and involved in tumorigenesis. AB - CDK4 is crucial for G1-to-S transition of cell cycle. It is well established that ubiquitin-mediated degradations of CDK inhibitors and cyclins are pivotal for the timely and unidirectional progression of cell cycle. However, how CDK4 itself is modulated by ubiquitin-mediated degradation has been elusive. Here we report that the steady-state level of CDK4 is controlled by PAQR4, a member of the progestin and adipoQ receptor family, and SKP2, an E3 ubiquitin ligase. Knockdown of PAQR4 leads to reduction of cell proliferation, accompanied by reduced protein level of CDK4. PAQR4 reduces polyubiquitination and degradation of CDK4. PAQR4 interacts with the C-terminal lobe of CDK4. On the other hand, SKP2 also interacts with the C-terminal lobe of CDK4 and enhances polyubiquitination and degradation of CDK4. Importantly, PAQR4 and SKP2 bind to the same region in CDK4, and PAQR4 competes with SKP2 for the binding, thereby abrogating SKP2-mediated ubiquitination of CDK4. Using a two-stage DMBA/TPA-induced skin cancer model, we find that PAQR4 deleted mice are resistant to chemical carcinogen-induced tumor formation. Collectively, our findings reveal that the steady-state level of CDK4 is controlled by the antagonistic actions between PAQR4 and SKP2, contributing to modulation of cell proliferation and tumorigenesis. PMID- 28992328 TI - What Parents Think About the Risks and Benefits of Antibiotics for Their Child's Acute Respiratory Tract Infection. AB - Background: Parental pressure is often cited as a reason for why pediatricians overuse antibiotics for children with acute respiratory tract infection (ARTI). We sought to capture parent perceptions of antibiotics at the time of their child's presentation with an ARTI. Methods: We conducted semistructured interviews with parents of children who presented with ARTI symptoms to 1 of 4 diverse practices in a large hospital-affiliated network of pediatric primary care practices. Parents were interviewed before their child was seen by the pediatrician and asked about their perceptions of antibiotics. Results: Interviews were conducted with 109 parents. None of the parents said they planned to ask the pediatrician for antibiotics but instead expected to gain reassurance and a plan to minimize symptoms. Three perceptions about antibiotics were identified: parents have a sense of wariness when their child is prescribed antibiotics, they have an understanding that antibiotic overuse is a problem but that it is driven by the demands of other parents, and they have a preference for alternative treatment. The majority of the parents were not concerned about antibiotic resistance. In response to closed-ended questions designed to assess their level of concern with adverse effects, parents were most concerned with their child developing an upset stomach, having an allergic reaction, and experiencing diarrhea. The parents were not concerned with antibiotic treatment failure. Conclusions: Parents in our study expressed a sense of caution about antibiotics and an awareness that they should be used judiciously. Our findings indicate that parents are aware of the downsides of antibiotics and might be willing to partner with healthcare providers to improve appropriate use. PMID- 28992326 TI - Neurological complications of new chemotherapy agents. AB - This last decade has yielded more robust development of cancer treatments and first-in-class agents than ever before. Since 2006, nearly one hundred new drugs have received regulatory approval for the treatment of hematological and solid organ neoplasms. Moreover, older conventional therapies have received approval for new clinical indications and are being used in combination with these newer small-molecule targeted treatments. The nervous system is vulnerable to many of the traditional cancer therapies, manifesting both already well-described acute and chronic toxicities. However, newer agents may produce toxicities that may seem indistinguishable from the underlying cancer. Early recognition of neurotoxicities from new therapeutics is vital to avoid irreversible neurological injury. This review focuses on cancer therapies in use in the last 10 years and approved by the FDA from January 2006 through January 1, 2017. PMID- 28992330 TI - Quantitative characterization of cuticular barrier properties: methods, requirements, and problems. AB - The interface between the atmosphere and leaves and fruits is formed by the lipophilic plant cuticle, which seals the outer epidermal cell walls, thus significantly reducing water loss and uptake of dissolved solutes deposited on the cuticle surface. Different experimental and theoretical approaches for quantifying barrier properties of cutinized leaf and fruit surfaces are presented and discussed in this review. Quantitative characterization of cuticle barrier properties requires (i) the measurement of diffusion kinetics, namely the amount diffusing versus time, (ii) accurate knowledge of driving forces, namely concentration gradients, acting across the barrier, and (iii) the calculation of permeances, namely diffusion velocity. We suggest that on the basis of permeances, which are independent from experimental boundary conditions such as driving forces, the time period of measurement, and area, cuticle barrier properties of different plant organs, different plant species, and different lines, as well as barrier properties of suberized root tissue or synthetic membranes, can be directly compared. This review provides a short and easy to understand manual on what should be kept in mind when quantifying barrier properties of cutinized and suberized transport barriers. This could be helpful for scientists working on cuticle biosynthesis and its regulation. PMID- 28992329 TI - Transcription factor CitERF71 activates the terpene synthase gene CitTPS16 involved in the synthesis of E-geraniol in sweet orange fruit. AB - The unique flavor of Citrus fruit depends on complex combinations of soluble sugars, organic acids, and volatile compounds. The monoterpene E-geraniol is an important volatile, contributing to flavor in sweet orange (Citrus sinensis Osbeck). Moreover, antifungal activity of E-geraniol has also been observed. However, the terpene synthase (TPS) responsible for its synthesis has not been identified in sweet orange. Terpene synthase 16 (CitTPS16) was shown to catalyze synthesis of E-geraniol in vitro, and transient overexpression of CitTPS16 in fruits and leaves of Newhall sweet orange resulted in E-geraniol accumulation in vivo. Having identified the responsible enzyme, we next examined transcriptional regulation of CitTPS16 in the fruit. Among cloned members of the AP2/ERF transcription factor gene family, CitERF71 showed a similar expression pattern to CitTPS16. Moreover, CitERF71 was able to activate the CitTPS16 promoter based on results from transient dual-luciferase assays and yeast one-hybrid assays. EMSAs showed that CitERF71 directly binds to ACCCGCC and GGCGGG motifs in the CitTPS16 promoter. These results indicate an important role for CitERF71 in transcriptional regulation of CitTP16 and, therefore, in controlling production of E-geraniol in Citrus fruit. PMID- 28992331 TI - Role of DNA polymerase beta oxidized nucleotide insertion in DNA ligation failure. AB - Production of reactive oxygen and nitrogen species (ROS), such as hydrogen peroxide, superoxide and hydroxyl radicals, has been linked to cancer, and these oxidative molecules can damage DNA. Base excision repair (BER), a major repair system maintaining genome stability over a lifespan, has an important role in repairing oxidatively induced DNA damage. Failure of BER leads to toxic consequences in ROS-exposed cells, and ultimately can contribute to the pathobiology of disease. In our previous report, we demonstrated that oxidized nucleotide insertion by DNA polymerase beta (pol beta) impairs BER due to ligation failure and leads to formation of a cytotoxic repair intermediate. Biochemical and cytotoxic effects of ligation failure could mediate genome stability and influence cancer therapeutics. In this review, we discuss the importance of coordination between pol beta and DNA ligase I during BER, and how this could be a fundamental mechanism underlying human diseases such as cancer and neurodegeneration. A summary of this work was presented in a symposium at the International Congress of Radiation Research 2015 in Kyoto, Japan. PMID- 28992332 TI - L-tyrosine induces the production of a pyomelanin-like pigment by the parasitic yeast-form of Histoplasma capsulatum. AB - Melanization of Histoplasma capsulatum remains poorly described, particularly in regards to the forms of melanin produced. In the present study, 30 clinical and environmental H. capsulatum strains were grown in culture media with or without L tyrosine under conditions that produced either mycelial or yeast forms. Mycelial cultures were not melanized under the studied conditions. However, all strains cultivated under yeast conditions produced a brownish to black soluble pigment compatible with pyomelanin when grew in presence of L-tyrosine. Sulcotrione inhibited pigment production in yeast cultures, strengthening the hyphothesis that H. capsulatum yeast forms produce pyomelanin. Since pyomelanin is produced by the fungal parasitic form, this pigment may be involved in H. capsulatum virulence. PMID- 28992333 TI - Rapid detection of fluconazole resistance in Candida tropicalis by MALDI-TOF MS. AB - With the changing epidemiology and emergence of antifungal resistance among Candida species, rapid antifungal susceptibility testing (AFST) is crucial for optimization of antifungal therapy. This study was conducted to standardize a matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI -TOF MS) based AFST method (ms-AFST) for susceptibility of Candida tropicalis isolates. Clinical isolates of C. tropicalis were confirmed for fluconazole resistance by the CLSI (M27-A3) method. The incubation period and drug concentration were optimized to determine the minimal profile change concentration (MPCC) by MALDI-TOF MS. The data were analyzed first by direct visual observation of the spectra followed by composite correlation index (CCI) matrix analysis, virtual gel analysis, and cluster analysis for confirmation. Finally, the correlation between minimum inhibitory concentrations (MICs) and MPCCs was evaluated. A total of 15 fluconazole resistant (MICs ranging from 16 to 128 MUg/ml) and 19 fluconazole susceptible C. tropicalis isolates (MIC <=1 MUg/ml) were included in this study. All C. tropicalis isolates had significant spectral changes after 4h incubation with fluconazole. Of 34 isolates, MPCCs and MICs were equivalent for 16 isolates, and the MPCC was one dilution lower than the respective MIC in the remaining 18 isolates. This finding was further supported by visual analysis, CCI matrix analysis, virtual gel and principal component analysis dendrogram analysis. The correlation between MPCC and MIC was significant (P < .05). Therefore, a MALDI-TOF MS based AFST assay may be used as a rapid screening technique for fluconazole resistance in C. tropicalis. PMID- 28992335 TI - How to set the stage for a full-fledged clinical trial testing 'incremental haemodialysis'. AB - Most people who make the transition to maintenance haemodialysis (HD) therapy are treated with a fixed dose of thrice-weekly HD (3HD/week) regimen without consideration of their residual kidney function (RKF). The RKF provides an effective and naturally continuous clearance of both small and middle molecules, plays a major role in metabolic homeostasis, nutritional status and cardiovascular health, and aids in fluid management. The RKF is associated with better patient survival and greater health-related quality of life. Its preservation is instrumental to the prescription of incremental (1HD/week to 2HD/week) HD. The recently heightened interest in incremental HD has been hindered by the current limitations of the urea kinetic model (UKM), which tend to overestimate the needed dialysis dose in the presence of a substantial RKF. A recent paper by Casino and Basile suggested a variable target model (VTM), which gives more clinical weight to the RKF and allows less frequent HD treatments at lower RKF as opposed to the fixed target model, based on the wrong concept of the clinical equivalence between renal and dialysis clearance. A randomized controlled trial (RCT) enrolling incident patients and comparing incremental HD (prescribed according to the VTM) with the standard 3HD/week schedule and focused on hard outcomes, such as survival and health-related quality of life of patients, is urgently needed. The first step in designing such a study is to compute the 'adequacy lines' and the associated fitting equations necessary for the most appropriate allocation of the patients in the two arms and their correct and safe follow-up. In conclusion, the potentially important clinical and financial implications of the incremental HD render it highly promising and warrant RCTs. The UKM is the keystone for conducting such studies. PMID- 28992334 TI - GmPHR25, a GmPHR member up-regulated by phosphate starvation, controls phosphate homeostasis in soybean. AB - As an essential nutrient element, phosphorus (P) plays an important role in plant growth and development. Low P availability is a limiting factor for crop production, especially for legume crops (e.g. soybean), which require additional P to sustain nitrogen fixation through symbiotic associations with rhizobia. Although PHOSPHATE STARVATION RESPONSE 1 (PHR1) or PHR1-like is considered as a central regulator of phosphate (Pi) homeostasis in several plant species, it remains undefined in soybean. In this study, 35 GmPHR members were cloned from the soybean genome and expression patterns in soybean were assayed under nitrogen (N) and P deficiency conditions. GmPHR25, which is up-regulated in response to Pi starvation, was then overexpressed in soybean hairy roots in vitro and in vivo to investigate its functions. The results showed that overexpressing GmPHR25 increased Pi concentration in transgenic soybean hairy roots under normal conditions, accompanied with a significant decrease in hairy root growth. Furthermore, transcripts of 11 out of 14 high-affinity Pi transporter (GmPT) members as well as five other Pi starvation-responsive genes were significantly increased in soybean hairy roots with GmPHR25 overexpression. Taken together, this study suggests that GmPHR25 is a vital regulator in the P signaling network, and controls Pi homeostasis in soybean. PMID- 28992336 TI - Molecular and cytogenetic effects of Thai royal jelly: modulation through c-MYC, h-TERT, NRF2, HO-1, BCL2, BAX and cyclins in human lymphocytes in vitro. AB - Royal jelly (RJ) is widely used as a food supplement for anti-aging and beauty. However, its use has been linked to asthma and hemorrhagic colitis. Since its mechanisms of toxicity have not been fully identified, we conducted an investigation to elucidate its molecular and cytogenetic effects. Using human lymphocytes in vitro, treatments with RJ (0.0005-5 mg/ml) for 3 h did not induce sister chromatid exchanges until 5 mg/ml was used. Treatments for 24 h showed a dose-dependent reduction in BCL2/BAX, c-MYC/BAX and HO-1/BAX ratios. The exception was the NRF2/BAX ratio, showing a dose-dependent reduction at low doses, but a marked increase at the highest dose. The hTERT/BAX ratio was maintained at approximately a 1.2-fold increase but decreased to nearly normal at the highest dose. Our findings indicated that the lowest dose of RJ treatment provided maximum benefits, mainly through hTERT activation relating to prolonged lifespan. The highest dose of RJ inhibited cell survival, cell proliferation and an antioxidative enzyme; nevertheless, it still activated an antioxidative response through NRF2 and maintained telomeres during cell crisis. RJ treatment at 0.05 mg/ml increased cyclin E, BCL2 and BAX to maximum levels indicating that throughout the active cell cycle, both cell survival and cell apoptosis increased. Using the gene expression ratios over BAX, similar to BCL2/BAX, provided more informative data than using individual protein levels alone. With these informative ratios, our results confirm the potential benefits of RJ in enhancing lifespan and activation antioxidative power. Further, in vivo mechanistic studies will be useful in validating these results. PMID- 28992337 TI - Occurrence and species distribution of pathogenic Mucorales in unselected soil samples from France. AB - Mucormycosis is a life-threatening invasive fungal disease that affects a variety of patient groups. Although Mucorales are mostly opportunistic pathogens originating from soil or decaying vegetation, there are currently few data on prevalence of this group of fungi in the environment. The aim of the present study was to assess the prevalence and diversity of species of Mucorales from soil samples collected in France. Two grams of soil were homogenized in sterile saline and plated on Sabouraud dextrose agar and RPMI agar supplemented with itraconazole or voriconazole. Both media contained chloramphenicol and gentamicin. The plates were incubated at 35 +/- 2 degrees C and checked daily for fungal growth for a maximum of 7 d. Mucorales were subcultured for purity. Each isolate was identified phenotypically and molecular identification was performed by ITS sequencing. A total of 170 soil samples were analyzed. Forty-one isolates of Mucorales were retrieved from 38 culture-positive samples. Among the recovered isolates, 27 Rhizopus arrhizus, 11 Mucor circinelloides, one Lichtheimia corymbifera, one Rhizopus microsporus and one Cunninghamella bertholletiae were found. Positive soil samples came from cultivated fields but also from other types of soil such as flower beds. Mucorales were retrieved from samples obtained in different geographical regions of France. Voriconazole containing medium improved the recovery of Mucorales compared with other media. The present study showed that pathogenic Mucorales are frequently recovered from soil samples in France. Species diversity should be further analyzed on a larger number of soil samples from different geographic areas in France and in other countries. PMID- 28992338 TI - The association of donor and recipient age with graft survival in paediatric renal transplant recipients in a European Society for Paediatric Nephrology/European Renal Association-European Dialysis and Transplantation Association Registry study. AB - Background: The impact of donor age in paediatric kidney transplantation is unclear. We therefore examined the association of donor-recipient age combinations with graft survival in children. Methods: Data for 4686 first kidney transplantations performed in 13 countries in 1990-2013 were extracted from the ESPN/ERA-EDTA Registry. The effect of donor and recipient age combinations on 5 year graft-failure risk, stratified by donor source, was estimated using Kaplan Meier survival curves and Cox regression, while adjusting for sex, primary renal diseases with a high risk of recurrence, pre-emptive transplantation, year of transplantation and country. Results: The risk of graft failure in older living donors (50-75 years old) was similar to that of younger living donors {adjusted hazard ratio [aHR] 0.74 [95% confidence interval (CI) 0.38-1.47]}. Deceased donor (DD) age was non-linearly associated with graft survival, with the highest risk of graft failure found in the youngest donor age group [0-5 years; compared with donor ages 12-19 years; aHR 1.69 (95% CI 1.26-2.26)], especially among the youngest recipients (0-11 years). DD age had little effect on graft failure in recipients' ages 12-19 years. Conclusions: Our results suggest that donations from older living donors provide excellent graft outcomes in all paediatric recipients. For young recipients, the allocation of DDs over the age of 5 years should be prioritized. PMID- 28992339 TI - STAT3 inhibition attenuates the progressive phenotypes of Alport syndrome mouse model. AB - Background: Alport syndrome (AS) is a hereditary, progressive nephritis caused by mutation of type IV collagen. Previous studies have shown that activation of signal transducer and activator of transcription 3 (STAT3) exacerbates other renal diseases, but whether STAT3 activation exacerbates AS pathology is still unknown. Here we aim to investigate the involvement of STAT3 in the progression of AS. Method: Phosphorylated STAT3 expression was assessed by immunoblotting analysis of kidneys and glomeruli of an AS mouse model (Col4a5 G5X mutant). To determine the effect of blocking STAT3 signaling, we treated AS mice with the STAT3 inhibitor stattic (10 mg/kg i.p., three times per week for 10 weeks; n = 10). We assessed the renal function [proteinuria, blood urea nitrogen (BUN), serum creatinine] and analyzed the glomerular injury score, fibrosis and inflammatory cell invasion by histological staining. Moreover, we analyzed the gene expression of nephritis-associated molecules. Results: Phosphorylated STAT3 was upregulated in AS kidneys and glomeruli. Treatment with stattic ameliorated the progressive renal dysfunction, such as increased levels of proteinuria, BUN and serum creatinine. Stattic also significantly suppressed the gene expression levels of renal injury markers (Lcn2, Kim-1), pro-inflammatory cytokines (Il-6, KC), pro-fibrotic genes (Tgf-beta, Col1a1, alpha-Sma) and Mmp9. Stattic treatment decreased the renal fibrosis congruently with the decrease of transforming growth factor beta (TGF-beta) protein and increase of antifibrosis-associated markers p Smad1, 5 and 8, which are negative regulators of TGF-beta signaling. Conclusion: STAT3 inhibition significantly ameliorated the renal dysfunction in AS mice. Our finding identifies STAT3 as an important regulator in AS progression and provides a promising therapeutic target for AS. PMID- 28992340 TI - Gremlin and renal diseases: ready to jump the fence to clinical utility? AB - The current therapeutic strategy for the treatment of chronic kidney diseases only ameliorates disease progression. During renal injury, developmental genes are re-expressed and could be potential therapeutic targets. Among those genes reactivated in the adult damaged kidney, Gremlin is of particular relevance since recent data suggest that it could be a mediator of diabetic nephropathy and other progressive renal diseases. Earlier studies have shown that Gremlin is upregulated in trans-differentiated renal proximal tubular cells and in several chronic kidney diseases associated with fibrosis. However, not much was known about the mechanisms by which Gremlin acts in renal pathophysiology. The role of Gremlin as a bone morphogenetic protein antagonist has clearly been demonstrated in organogenesis and in fibrotic-related disorders. Gremlin binds to vascular endothelial growth factor receptor 2 (VEGFR2) in endothelial and tubular epithelial cells. Activation of the Gremlin-VEGFR2 axis was found in several human nephropathies. We have recently described that Gremlin activates the VEGFR2 signaling pathway in the kidney, eliciting a downstream mechanism linked to renal inflammatory response. Gremlin deletion improves experimental renal damage, diminishing fibrosis. Overall, the available data identify the Gremlin-VEGFR2 axis as a novel therapeutic target for kidney inflammation and fibrosis and provide a rationale for unveiling new concepts to investigate in several clinical conditions. PMID- 28992342 TI - The endoplasmic reticulum is a hub to sort proteins toward unconventional traffic pathways and endosymbiotic organelles. AB - The discovery that much of the extracellular proteome in eukaryotic cells consists of proteins lacking a signal peptide, which cannot therefore enter the secretory pathway, has led to the identification of alternative protein secretion routes bypassing the Golgi apparatus. However, proteins harboring a signal peptide for translocation into the endoplasmic reticulum can also be transported along these alternative routes, which are still far from being well elucidated in terms of the molecular machineries and subcellular/intermediate compartments involved. In this review, we first try to provide a definition of all the unconventional protein secretion pathways in eukaryotic cells, as those pathways followed by proteins directed to an 'external space' bypassing the Golgi, where 'external space' refers to the extracellular space plus the lumen of the secretory route compartments and the inner space of mitochondria and plastids. Then, we discuss the role of the endoplasmic reticulum in sorting proteins toward unconventional traffic pathways in plants. In this regard, various unconventional pathways exporting proteins from the endoplasmic reticulum to the vacuole, plasma membrane, apoplast, mitochondria, and plastids are described, including the short routes followed by the proteins resident in the endoplasmic reticulum. PMID- 28992341 TI - A Prospective Study of Inflammatory Markers and Risk of Endometriosis. AB - Much evidence suggests a role for inflammation in the pathogenesis of endometriosis. Although investigators in numerous case-control studies have found elevation of inflammatory markers in patients with endometriosis, results were not consistent, and no prior prospective study is known to exist. We conducted a case-control study nested within the Nurses' Health Study II in which we examined associations between levels of plasma inflammatory markers (interleukin-1 beta, interleukin-6, soluble tumor necrosis factor alpha receptors 1 and 2, and high sensitivity C-reactive protein) and the risk of laparoscopically confirmed endometriosis. From blood collections in 1996-1999 and 2007, we ascertained 350 cases patients with incident endometriosis and 694 matched controls. Women with interleukin-1 beta levels in quintiles 2-4 had a higher risk of endometriosis (for the second quintile, relative risk (RR) = 3.30, 95% confidence interval (CI): 1.06, 10.3; for the third quintile, RR = 3.36, 95% CI: 1.09, 10.4; and for the fourth quintile, RR = 4.64, 95% CI: 1.58, 13.6; P for trend = 0.62), which suggested an association beginning at 0.47 pg/mL or greater. A significant nonlinear association with levels of soluble tumor necrosis factor alpha receptor 2 was observed, with elevated risk of endometriosis at concentrations greater than 3,400 pg/mL. Plasma interleukin-6, soluble tumor necrosis factor alpha receptor 1, and high-sensitivity C-reactive protein levels were not associated with endometriosis risk. Further research in larger studies with younger age at blood collection and longer time from blood to surgical diagnosis are required to confirm these associations. PMID- 28992343 TI - Serum-to-dialysate potassium gradient and its association with short-term outcomes in hemodialysis patients. AB - Background: A high serum-to-dialysate potassium (K+) gradient at the start of dialysis leads to rapid lowering of serum K+ and may confer a greater risk of adverse events. Here, we examined the near-term association of K+ gradient with clinical outcomes. Methods: This retrospective (2010-11) event-based study considered 830 741 patient-intervals, each defined by a pre-dialysis measurement of serum K+ made among adult Medicare Parts A and B enrollees who received in center hemodialysis on a Monday/Wednesday/Friday schedule at a large US dialysis organization. K+ gradient was considered based on the difference in K+ concentration (serum-dialysate) on the date of measurement; analyses accounted for multiple observations per patient. Outcomes considered were: all-cause and cardiovascular hospital admissions, emergency department (ED) visits and deaths. Results: Higher K+ gradient was associated with younger age, greater fistula use, lower comorbidity scores and better nutritional indices. Adjusting for patient differences, there was a dose-response relationship between higher K+ gradient and greater risks of all-cause hospitalization and ED visit. A similar trend was seen for cardiovascular hospitalization but did not achieve statistical significance. No associations were observed with mortality, potentially due to a low number of events. Conclusions: Higher K+ gradient is independently associated with greater risk of all-cause hospitalizations and ED visits. Further research is needed to determine whether interventions that reduce the K+ gradient ameliorate this risk. PMID- 28992344 TI - Neural Circuitry That Mediates Behavior Governing the Tradeoffs Between Survival and Reproduction in Caenorhabditis elegans. AB - In all outcrossing sexual species there is a mechanism that brings two parents together. For animals, this reproductive requirement may at times conflict with other needs, such as foraging for food. This tension has been studied using the tiny (1 mm) nematode worm, Caenorhabditis elegans. In a trade off between certainty of survival and possibility of reproduction, the C. elegans male will abandon a food patch lacking mates and explore its environment to find one where mates are present. A quantitative behavioral assay has been used to study the behavioral mechanism of mate searching and nutritional, sexual, and neurohormonal pathways that influence the underlying drive state. Taking advantage of the known connectivity of the C. elegans nervous system, neural pathways have been identified that influence the male's behavior in the presence of food with and without mates. PMID- 28992345 TI - EjNAC3 transcriptionally regulates chilling-induced lignification of loquat fruit via physical interaction with an atypical CAD-like gene. AB - Lignin is an important component of many plant secondary cell walls. In the fruit of loquat (Eriobotrya japonica), lignification of cell walls in the fleshy tissue occurs when fruit are subjected to low-temperature storage, which is commonly used to avoid the rapid senescence that occurs at room temperature. In this study, two NAC domain genes, EjNAC3 and EjNAC4, were isolated and shown to be significantly induced at 0 degrees C, which was concomitant with an increase in the fruit lignification index. Lignification and expression of both EjNAC3 and EjNAC4 were inhibited by low-temperature conditioning and by heat treatment. In addition, EjNAC3 trans-activated the lignin biosynthesis-related EjCAD-like promoter, which was measured using a dual-luciferase assay. Further analysis with yeast one-hybrid and electrophoretic mobility shift assays indicated that EjNAC3 could physically bind to the promoter of the EjCAD-like gene. Thus, EjNAC3 is a direct regulator of loquat chilling-induced lignification, via regulations of EjCAD-like. PMID- 28992346 TI - Searching for assay controls for the Fpg- and hOGG1-modified comet assay. AB - The formamidopyrimidine DNA glycosylase (Fpg) and human 8-oxoguanine DNA glycosylase (hOGG1)-modified comet assays have been widely used in human biomonitoring studies. The purpose of this article is to assess differences in reported levels of Fpg- and hOGG1-sensitive sites in leukocytes and suggest suitable assay controls for the measurement of oxidatively damaged DNA. An assessment of the literature showed a large variation in the reported levels of Fpg-sensitive sites (range 0.05-1.31 lesions/106 bp). The levels of Fpg-sensitive sites are lower in studies where Fpg has been obtained from commercial suppliers or unknown sources as compared to Fpg from one particular non-commercial source (chi2 = 7.14, P = 0.028). The levels of hOGG1-sensitive sites are lower (range: 0.04-0.18 lesions/106 bp in leukocytes) compared to the Fpg-sensitive sites. Surprisingly, few publications have reported the use of oxidising agents as assay controls, with the exception of hydrogen peroxide. This may be due to a lack of consensus about suitable controls for the Fpg- and hOGG1-modified comet assay. A major challenge is to find an oxidising agent that only oxidises nucleobases and does not generate DNA strand breaks because this reduces the dynamic range of Fpg and hOGG1-sensitive sites in the comet assay. Based on a literature search we selected the photosensitiser Ro19-8022 plus light, KBrO3, 4-nitroquinoline-1 oxide, Na2Cr2O7 and ferric nitrilotriacetate as possible assay controls. A subsequent assessment of these compounds for generating cryopreserved assay controls in mononuclear blood cells showed that Ro19-8022 plus light, KBrO3 and 4 nitroquinoline-1-oxide provided suitable assay controls. We recommend these compounds as comet assay controls for oxidatively damaged DNA. PMID- 28992347 TI - Common molecular pathogenesis of disease-related intrinsically disordered proteins revealed by NMR analysis. AB - Intrinsically disordered proteins (IDPs) are either completely unstructured or contain large disordered regions in their native state; they have drawn much attention in the field of molecular pathology. Some of them substantially tend to form protein self-assemblies, such as toxic or non-toxic aggregates and fibrils, and have been postulated to relate to diseases. These disease-related IDPs include Abeta(1-42) [Alzheimer's disease (AD)], Tau (AD and tauopathy), alpha synuclein (Parkinson's disease) and p53 (cancer). Several studies suggest that these aggregation and/or fibril formation processes are often initiated by transient conformational changes of the IDPs prior to protein self-assembly. Interestingly, the pathological molecular processes of these IDPs share multiple common features with those of protein misfolding diseases, such as transmissible spongiform encephalopathy (PrPsc) and AL-amyloidosis (VL-domain of gamma immunoglobulin). This review provides an overview of solution NMR techniques that can help analyse the early and transient events of conformational equilibrium of IDPs and folded proteins. PMID- 28992348 TI - Location of glomerular immune deposits, not codeposition of immunoglobulin G, influences definitive renal outcomes in immunoglobulin A nephropathy. AB - Background: It has been suggested that the prognosis of immunoglobulin (IgA) nephropathy (IgAN) is adversely affected if there is codeposition of IgG in the glomeruli or if immune deposits are present in the glomerular capillary walls. We sought to understand how these variables affect clinical outcome. Methods: A total of 80 IgAN biopsies were retrospectively divided into groups: (i) IgA without IgG deposition versus IgA + IgG and (ii) immune deposits restricted to the mesangium versus mesangium and peripheral capillary walls (PCWs). The association of these groups with the composite primary outcome of renal replacement therapy, renal transplant, death or doubling of serum creatinine (SCr) concentration was determined. The change in estimated glomerular filtration rate (eGFR) was also assessed. Covariates examined were age, sex, race, SCr and proteinuria level at biopsy and at follow-up, duration of follow-up, treatment, Oxford score and presence of crescents. Results: IgG codeposition showed a trend toward endocapillary hypercellularity (P = 0.082); there were no other baseline differences between the IgA (n = 55) and IgA + IgG (n = 25) groups. At a median follow-up time of 29 months, the combined primary outcome was reached in 24 patients, 16 with IgA and 8 with IgA + IgG (P = 0.82). Patients with immune deposits in the PCWs (n = 21) presented with higher baseline proteinuria than those with deposits limited to the mesangium (n = 59; P = 0.025), were more likely to have crescents/segmental glomerular necrosis on biopsy (P = 0.047) and were more likely to reach the combined primary outcome (P = 0.026). Biopsies with crescents/segmental glomerular necrosis were associated with endocapillary hypercellularity (P < 0.001). Conclusions: In this multicenter IgAN cohort, IgG co-deposition and the location of glomerular immune deposits in the PCWs were both associated with greater histologic activity on renal biopsy, but only the location of glomerular immune deposits in the PCWs was associated with a significantly increased risk for end-stage renal disease, transplant, death and/or doubling of SCr. PMID- 28992349 TI - Singing and Vocal Interventions in Palliative and Cancer Care: Music Therapists' Perceptions of Usage. AB - Background: Music therapists in palliative and cancer care settings often use singing and vocal interventions. Although benefits for these interventions are emerging, more information is needed on what type of singing interventions are being used by credentialed music therapists, and what goal areas are being addressed. Objective: To assess music therapists' perceptions on how they use singing and vocal interventions in palliative and cancer care environments. Method: Eighty credentialed music therapists from Canada and the United States participated in this two-part convergent mixed-methods study that began with an online survey, followed by individual interviews with 50% (n = 40) of the survey participants. Results: In both palliative and cancer care, singing client preferred music and singing for relaxation were the most frequently used interventions. In palliative care, the most commonly addressed goals were to increase self-expression, improve mood, and create a feeling of togetherness between individuals receiving palliative care and their family. In cancer care, the most commonly addressed goals were to support breathing, improve mood, and support reminiscence. Seven themes emerged from therapist interviews: containing the space, connection, soothing, identity, freeing the voice within, letting go, and honoring. Conclusions: Music therapists use singing to address the physical, emotional, social, and spiritual goals of patients, and described singing interventions as accessible and effective. Further research is recommended to examine intervention efficacy and identify factors responsible that contribute to clinical benefit. PMID- 28992350 TI - Radon inhalation induces manganese-superoxide dismutase in mouse brain via nuclear factor-kappaB activation. AB - Although radon inhalation increases superoxide dismutase (SOD) activities in mouse organs, the mechanisms and pathways have not yet been fully clarified. The aim of this study was to determine the details of SOD activation in mouse brain tissue following the inhalation of radon at concentrations of 500 or 2000 Bq/m3 for 24 h. After inhalation, brains were removed quickly for analysis. Radon inhalation increased the manganese (Mn)-SOD level and mitochondrial SOD activity. However, the differences were not significant. There were no changes in the Cu/Zn SOD level or cytosolic SOD activity. Radon inhalation increased the brain nuclear factor (NF)-kappaB content, which regulates the induction of Mn-SOD, in the nuclear and cytosolic compartments. The level of inhibitor of nuclear factor kappaB kinase subunit beta (IKK-beta), which activates NF-kappaB, was slightly increased by radon inhalation. The expression of cytoplasmic ataxia telangiectasia mutated kinase in mice inhaling radon at 500 Bq/m3 was 50% higher than in control mice. In addition, NF-kappaB-inducing kinase was slightly increased after inhaling radon at 2000 Bq/m3. These findings suggest that radon inhalation might induce Mn-SOD protein via NF-kappaB activation that occurs in response to DNA damage and oxidative stress. PMID- 28992351 TI - Modification of meiotic recombination by natural variation in plants. AB - Meiosis is a specialized cell division that produces haploid gametes required for sexual reproduction. During the first meiotic division, homologous chromosomes pair and undergo reciprocal crossing over, which recombines linked sequence variation. Meiotic recombination frequency varies extensively both within and between species. In this review, we will examine the molecular basis of meiotic recombination rate variation, with an emphasis on plant genomes. We first consider cis modification caused by polymorphisms at the site of recombination, or elsewhere on the same chromosome. We review cis effects caused by mismatches within recombining joint molecules, the effect of structural hemizygosity, and the role of specific DNA sequence motifs. In contrast, trans modification of recombination is exerted by polymorphic loci encoding diffusible molecules, which are able to modulate recombination on the same and/or other chromosomes. We consider trans modifiers that act to change total recombination levels, hotspot locations, or interactions between homologous and homeologous chromosomes in polyploid species. Finally, we consider the significance of genetic variation that modifies meiotic recombination for adaptation and evolution of plant species. PMID- 28992352 TI - In vivo pathogenicity of Trichosporon asahii isolates with different in vitro enzymatic profiles in an immunocompetent murine model of systemic trichosporonosis. AB - Trichosporon asahii is an opportunistic yeastlike fungus that colonizes the gastrointestinal and respiratory tracts and human skin. Although it is an important cause of disseminated infections by non-Candida species, there are a few reports related to its virulence factors and their possible role in in vivo pathogenicity. We developed a murine model of disseminated trichosporonosis in immunocompetent mice for the evaluation of the in vivo pathogenicity of 6 T. asahii isolates with different in vitro virulence factor profiles. Tissue fungal burden was determined on days 1, 3, 7, 15, and 25 post-challenge. Overall, the largest fungal load was detected in the kidney on the 5 experimental days, while brain, spleen, and liver displayed a comparatively low fungal count. We observed a fungal burden decrease in most experimental groups from day 15. Histological analysis showed the presence of T. asahii in tissue and a generalized inflammatory infiltrate of polymorphonuclear cells in the kidney, liver, red pulp of the spleen, and the hippocampus. Even though our isolates showed different in vitro virulence factors profiles, we did not detect relevant differences when assayed in vivo, except for a higher persistence of a protease- and biofilm producing strain in kidney, liver, and brain. PMID- 28992353 TI - Glomerular mannose-binding lectin deposition in intrinsic antigen-related membranous nephropathy. AB - Background: The M-type phospholipase A2 receptor (PLA2R) and thrombospondin type 1 domain-containing 7A (THSD7A) were identified as intrinsic antigens in primary membranous nephropathy (MN). Complement activation via the lectin pathway in intrinsic antigen-related MN is still unclear. Methods: We retrospectively enrolled 60 primary Japanese MN patients and detected activated complement pathways by staining complement proteins in glomerular deposition. According to the findings of PLA2R and THSD7A staining in glomeruli, they were classified into intrinsic antigen-related or -unrelated MN. We evaluated clinicopathological characteristics and predictors of clinical outcomes in intrinsic antigen-related MN. Results: Thirty-nine (65%) patients had PLA2R in glomerular deposits and two (3.3%) patients had THSD7A. One of them had both PLA2R and THSD7A (double positive). Forty patients were classified into the intrinsic antigen-related group. The other 20 patients were negative for both antigens (unrelated group). The prevalence and staining intensity of mannose-binding lectin (MBL) deposits were much higher in the intrinsic antigen-related group [55% versus 20%, P < 0.010, 1.0 (interquartile range 1.0-2.0) versus 1.0 (0.0-1.0), P = 0.01, respectively]. The staining intensity of MBL in glomeruli also correlated with the IgG4 staining intensity. In intrinsic antigen-related MN, MBL staining intensity was an unfavorable predictor for remission of proteinuria [hazard ratio (HR) 0.40, P < 0.01] and renal dysfunction (HR 3.81, P = 0.01) in Cox proportional hazards analysis. Moreover, the glomerular MBL-positive group showed more severe interstitial fibrosis and worse clinical outcomes. Conclusions: Intrinsic antigen-related MN was more strongly associated with complement activation by the lectin pathway, which may contribute to a less favorable clinical outcome. PMID- 28992355 TI - Severe obesity is a limitation for the use of body mass index standard deviation scores in children and adolescents. AB - AIM: We analysed the distribution of the body mass index standard deviation scores (BMI-SDS) in children and adolescents seeking treatment for severe obesity, according to the International Obesity Task Force (IOTF), World Health Organization (WHO) and the national Norwegian Bergen Growth Study (BGS) BMI reference charts and the percentage above the International Obesity Task Force 25 cut-off (IOTF-25). METHODS: This was a cross-sectional study of 396 children aged four to 17 years, who attended a tertiary care obesity centre in Norway from 2009 to 2015. Their BMI was converted to SDS using the three growth references and expressed as the percentage above IOTF-25. The percentage of body fat was assessed by bioelectrical impedance analysis. RESULTS: Regardless of which BMI reference chart was used, the BMI-SDS was significantly different between the age groups, with a wider range of higher values up to 10 years of age and a more narrow range of lower values thereafter. The distributions of the percentage above IOTF-25 and percentage of body fat were more consistent across age groups. CONCLUSIONS: Our findings suggest that it may be more appropriate to use the percentage above a particular BMI cut-off, such as the percentage above IOTF-25, than the IOTF, WHO and BGS BMI-SDS in paediatric patients with severe obesity. PMID- 28992354 TI - Obesity and synergistic risk factors for chronic kidney disease in African American adults: the Jackson Heart Study. AB - Background: African Americans are at high risk for chronic kidney disease (CKD). Obesity may increase the risk for CKD by exacerbating features of the metabolic syndrome and promoting glomerular hyperfiltration. Whether other factors also affecting these pathways may amplify or mitigate obesity-CKD associations has not been investigated. Methods: We studied interactions between obesity and these candidate factors in 2043 African Americans without baseline kidney disease enrolled in the Jackson Heart Study. We quantified obesity as body mass index (BMI), sex-normalized waist circumference and visceral adipose volume measured by abdominal computed tomography at an interim study visit. Interactions were hypothesized with (i) metabolic risk factors (dietary quality and physical activity, both quantified by concordance with American Heart Association guidelines) and (ii) factors exacerbating or mitigating hyperfiltration (dietary protein intake, APOL1 risk status and use of renin-angiotensin system blocking medications). Using multivariable regression, we evaluated associations between obesity measures and incident CKD over the follow-up period, as well as interactions with metabolic and hyperfiltration factors. Results: Assessed after a median of 8 years (range 6-11 years), baseline BMI and waist circumference were not associated with incident CKD. Higher visceral adipose volume was independently associated with incident CKD (P = 0.008) in a nonlinear fashion, but this effect was limited to those with lower dietary quality (P = 0.001; P interaction = 0.04). In additional interaction models, higher waist circumference was associated with greater risk of incident CKD among those with the low-risk APOL1 genotype (P = 0.04) but not those with a high-risk genotype (P-interaction = 0.02). Other proposed factors did not modify obesity-CKD associations. Conclusions. Higher risks associated with metabolically active visceral adipose volume and interactions with dietary quality suggest that metabolic factors may be key determinants of obesity-associated CKD risk. Interactions between obesity and APOL1 genotype should be considered in studies of African Americans. PMID- 28992356 TI - UPLC-HR-MS/MS-based determination study on the metabolism of four synthetic cannabinoids, ADB-FUBICA, AB-FUBICA, AB-BICA and ADB-BICA, by human liver microsomes. AB - Since 2012, several cannabimimetic indazole and indole derivatives with valine amino acid amide residue have emerged in the illicit drug market, and have gradually replaced the old generations of synthetic cannabinoids (SCs) with naphthyl or adamantine groups. Among them, ADB-FUBICA [N-(1-amino-3,3-dimethyl-1 oxobutan-2-yl)-1-(4-fluorobenzyl)-1H-indole-3-carboxamide], AB-FUBICA [N-(1-amino 3-methyl-1-oxobutan-2-yl)-1-(4-fluorobenzyl)-1H-indole-3-carboxamide], AB-BICA [N (1-amino-3-methyl-1-oxobutan-2-yl)-1-benzyl-1H-indole-3-carboxamide] and ADB-BICA [N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-benzyl-1H-indole-3-carboxamide] were detected in China recently, but unfortunately no information about their in vitro human metabolism is available. Therefore, biomonitoring studies to screen their consumption lack any information about the potential biomarkers (e.g. metabolites) to target. To bridge this gap, we investigated their phase I metabolism by incubating with human liver microsomes, and the metabolites were identified by ultra-performance liquid chromatography-high resolution-tandem mass spectrometry. Metabolites generated by N-dealkylation and hydroxylation on the 1 amino-alkyl moiety were found to be predominant for all these four substances, and others which underwent hydroxylation, amide hydrolysis and dehydrogenation were also observed in our investigation. Based on our research, we recommend that the N-dealkylation and hydroxylation metabolites are suitable and appropriate analytical markers for monitoring their intake. PMID- 28992357 TI - Estimated depth of apatite and collagen degradation in human dentine by sequential exposure to sodium hypochlorite and EDTA: a quantitative FTIR study. AB - AIM: To characterize chemical degradation of the principal constituents of dentine after exposure to NaOCl and EDTA using Infrared Spectroscopy (ATR-FTIR). METHODOLOGY: Ground dentine particles, from extracted permanent human molars, were passed through sieves of 38 to 1 000 MUm to provide six size ranges. Portions (250 mg) of each size range were reacted with 5 mL of 2.5% NaOCl for 2 10 min; or 17% EDTA for 5-1440 min. Powders larger than 75 MUm were also sequentially exposed to NaOCl/EDTA/NaOCl each for 10 min. All experiments were repeated five times. Reacted and unreacted powders were washed and dried. Particles larger than 75 MUm were then reground. FTIR spectra of unground and reground reacted particles enabled assessment of particle surface versus bulk chemistry, respectively, plus estimation of reaction depth. Changes in the ratio of the 1 640 cm-1 collagen: 1 010 cm-1 phosphate peak height or its inverse were obtained. These were used to estimate surface and bulk fraction reacted and thus depth to which collagen or phosphate was reduced following immersion in NaOCl or EDTA, respectively. The data were analysed descriptively. RESULTS: Surface collagen fraction declined by ~40% within 2 min of NaOCl exposure, and plateaued at ~60% between 6-10 min. Bulk spectra showed average depth of collagen loss at 10 min was 16 +/- 13 MUm. Ten minute EDTA exposure caused ~60% loss of surface phosphate. Average depth of phosphate loss was 19 +/- 12 MUm and 89 +/- 43 MUm after 10 and 1 440 min EDTA immersion, respectively. Sequential NaOCl/EDTA immersion yielded a 62 +/- 28 MUm thick phosphate-depleted surface. Sequential NaOCl/EDTA/NaOCl treatment resulted in approximately 85 MUm of collagen loss. CONCLUSIONS: Data revealed the sequential depletion of collagen by NaOCl and apatite by EDTA in dentine, simultaneously exposing the other moieties. Alternate exposure to NaOCl and EDTA therefore enhances the depth of erosion. PMID- 28992359 TI - A study of CDR3 loop dynamics reveals distinct mechanisms of peptide recognition by T-cell receptors exhibiting different levels of cross-reactivity. AB - T-cell receptors (TCRs) can productively interact with many different peptides bound within the MHC binding groove. This property varies with the level of cross reactivity of TCRs; some TCRs are particularly hyper cross-reactive while others exhibit greater specificity. To elucidate the mechanism behind these differences, we studied five TCRs in complex with the same class II MHC (1Ab )-peptide (3K), that are known to exhibit different levels of cross-reactivity. Although these complexes have similar binding affinities, the interface areas between the TCR and the peptide-MHC (pMHC) differ significantly. We investigated static and dynamic structural features of the TCR-pMHC complexes and of TCRs in a free state, as well as the relationship between binding affinity and interface area. It was found that the TCRs known to exhibit lower levels of cross-reactivity bound to pMHC using an induced-fitting mechanism, forming large and tight interfaces rich in specific hydrogen bonds. In contrast, TCRs known to exhibit high levels of cross-reactivity used a more rigid binding mechanism where non specific pi-interactions involving the bulky Trp residue in CDR3beta dominated. As entropy loss upon binding in these highly degenerate and rigid TCRs is smaller than that in less degenerate TCRs, they can better tolerate changes in residues distal from the major contacts with MHC-bound peptide. Hence, our dynamics study revealed that differences in the peptide recognition mechanisms by TCRs appear to correlate with the levels of T-cell cross-reactivity. PMID- 28992358 TI - Role of Galectin-3 in the pathophysiology underlying allergic lung inflammation in a tissue inhibitor of metalloproteinases 1 knockout model of murine asthma. AB - Asthma is a chronic inflammatory respiratory disease characterized by airway inflammation, airway hyperresponsiveness and reversible airway obstruction. Understanding the mechanisms that underlie the various endotypes of asthma could lead to novel and more personalized therapies for individuals with asthma. Using a tissue inhibitor of metalloproteinases 1 (TIMP-1) knockout murine allergic asthma model, we previously showed that TIMP-1 deficiency results in an asthma phenotype, exhibiting airway hyperreactivity, enhanced eosinophilic inflammation and T helper type 2 cytokine gene and protein expression following sensitization with ovalbumin. In the current study, we compared the expression of Galectins and other key cytokines in a murine allergic asthma model using wild-type and TIMP-1 knockout mice. We also examined the effects of Galectin-3 (Gal-3) inhibition on a non-T helper type 2 cytokine interleukin-17 (IL-17) to evaluate the relationship between Gal-3 and the IL-17 axis in allergic asthma. Our results showed a significant increase in Gal-3, IL-17 and transforming growth factor-beta1 gene expression in lung tissue isolated from an allergic asthma murine model using TIMP-1 knockout. Gal-3 gene and protein expression levels were also significantly higher in lung tissue from an allergic asthma murine model using TIMP-1 knockout. Our data show that Gal-3 may regulate the IL-17 axis and play a pivotal role in the modulation of inflammation during experimental allergic asthma. PMID- 28992361 TI - Editorial: Thank you. PMID- 28992360 TI - Genetic diversity and worldwide distribution of the deltavirus genus: A study of 2,152 clinical strains. AB - : Hepatitis delta virus (HDV) is responsible for the most severe form of acute and chronic viral hepatitis. We previously proposed that the Deltavirus genus is composed of eight major clades. However, few sequences were available to confirm this classification. Moreover, little is known about the structural and functional consequences of HDV variability. One practical consequence is the failure of most quantification assays to properly detect or quantify plasmatic HDV RNA. Between 2001 and 2014, 2,152 HDV strains were prospectively collected and genotyped in our reference laboratory by means of nucleotide sequencing and extensive phylogenetic analyses of a 400-nucleotide region of the genome (R0) from nucleotides 889 to 1289 encompassing the 3' end of the delta protein-coding gene. In addition, the full-length genome sequence was generated for 116 strains selected from the different clusters, allowing for in-depth characterization of the HDV genotypes and subgenotypes. This study confirms that the HDV genus is composed of eight genotypes (HDV-1 to HDV-8) defined by an intergenotype similarity >85% or >80%, according to the partial or full-length genome sequence, respectively. Furthermore, genotypes can be segregated into two to four subgenotypes, characterized by an intersubgenotype similarity >90% (>84% for HDV 1) over the whole genome sequence. Systematic analysis of genome and protein sequences revealed highly conserved functional nucleotide and amino acid motifs and positions across all (sub)genotypes, indicating strong conservatory constraints on the structure and function of the genome and the protein. CONCLUSION: This study provides insight into the genetic diversity of HDV and a clear view of its geographical localization and allows speculation as to the worldwide spread of the virus, very likely from an initial African origin. (Hepatology 2017;66:1826-1841). PMID- 28992362 TI - The Editor recommends this issue's article to the reader: Long-term treatment outcomes in immature permanent teeth by revascularisation using MTA and GIC as canal-sealing materials: a retrospective study. PMID- 28992363 TI - Revisiting the challenge of intentional value shift: reply to Ives and Fischer. PMID- 28992364 TI - Behavioral Changes in Children After Emergency Department Procedural Sedation. AB - OBJECTIVE: The purpose of this study was to determine the proportion of children undergoing procedural sedation for fracture reduction in the emergency department (ED) observed to experience negative postdischarge behaviors. Predictors of negative behaviors were evaluated, including anxiety. METHODS: This was a prospective cohort study of children receiving intravenous ketamine sedation for ED fracture reduction. The child's anxiety prior to sedation was measured with the Modified Yale Preoperative Anxiety Scale. Negative behavioral changes were measured with the Post-Hospitalization Behavior Questionnaire 1 to 2 weeks after discharge. Descriptive statistics and odds ratios (ORs) were calculated. Chi square test was used for comparisons between groups. Multivariable logistic regression models evaluated predictors of negative behavioral change after discharge. RESULTS: Ninety-seven patients were enrolled; 82 (85%) completed follow-up. Overall, 33 (40%) children were observed to be highly anxious presedation and 18 (22%) had significant negative behavior changes after ED discharge. Independent predictors for negative behaviors were high anxiety (OR = 9.0, 95% confidence interval [CI] = 2.3-35.7) and nonwhite race (OR = 6.5, 95% CI = 1.7-25.0). CONCLUSION: For children undergoing procedural sedation in the ED, two in five children have high preprocedure anxiety and almost one in four have significant negative behaviors 1 to 2 weeks after discharge. Highly anxious and nonwhite children have increased risk of negative behavioral changes that have not been previously recognized in the ED setting. PMID- 28992365 TI - Familial Mediterranean Fever and Incidence of Cancer: An Analysis of 8,534 Israeli Patients With 258,803 Person-Years. AB - OBJECTIVE: Familial Mediterranean fever (FMF) is an autoinflammatory disease manifested as recurrent serosal inflammation. An association between FMF and malignancy has not been evaluated. The aim of this study was to estimate cancer risk in a large cohort of FMF patients from a single institution. METHODS: The study cohort consisted of 8,534 FMF patients registered at the National FMF Center in Tel Hashomer, Israel. We linked the study cohort to the database of the Israel National Cancer Registry using the national identity number. Cancer incidence in FMF patients was determined and then stratified by age and sex. Standardized incidence ratios (SIRs) for cancers were calculated. RESULTS: Among 8,534 FMF patients (4,400 men, 4,134 women), 350 developed cancer during the years 1970-2011. The overall cancer risk among patients with FMF was significantly lower than was expected in specific sex and ethnic groups of the Israeli population: for males of Jewish ethnicity, SIR 0.66 (95% confidence interval [95% CI] 0.55-0.77), P < 0.001; for females of Jewish ethnicity, SIR 0.75 (95% CI 0.64-0.86), P < 0.001; and for males of Arab ethnicity, SIR 0.34 (95% CI 0.07-0.99), P = 0.024. CONCLUSION: FMF patients have a significantly lower incidence of cancer than the general population of Israel. This pattern was demonstrated in 2 ethnic populations: Jewish and Arab. We speculate that the lower cancer incidence could be attributed to a direct physiologic effect of FMF or to its treatment. PMID- 28992368 TI - Unilateral plantar erythema nodosum in sarcoidosis. PMID- 28992366 TI - Possible involvement of the glucocorticoid receptor (NR3C1) and selected NR3C1 gene variants in regulation of human testicular function. AB - Perceived stress has been associated with decreased semen quality but the mechanisms have not been elucidated. It is not known whether cortisol, the major stress hormone in humans, can act directly via receptors in the testis, and whether variants in the gene encoding the glucocorticoid receptor (NR3C1) can possibly modulate the effect. To address these questions, we investigated the expression of the glucocorticoid receptor in human testicular tissue, including adult and fetal samples (n = 20) by immunohistochemical staining, and in silico analysis of publicly available datasets. In the adult testis NR3C1 protein was detected in peritubular cells, a subset of Leydig cells, Sertoli cells (weak), and spermatogonia, but not in spermatids. The NR3C1 expression pattern in fetal testis samples differed by a notably stronger reaction in Sertoli cells, lack of staining in gonocytes but the presence in a subset of pro-spermatogonia, and the almost absent reaction in nascent peritubular cells. In parallel, we explored the association between adult testicular function and three single nucleotide NR3C1 polymorphisms (BcII [rs41423247], 9beta [rs6198], and Tth111I [rs10052957]) affecting glucocorticoid sensitivity. Testicular function was determined by semen analysis and reproductive hormone profiling in 893 men from the general population. The NR3C1 SNP BclI was associated with semen quality in an over dominant manner with heterozygotes having better semen parameters compared to both homozygote constellations, and with sperm motility showing the strongest association. This association was supported by a higher inhibin B and inhibin B/FSH ratio, as well as a lower FSH in BclI heterozygotes. The SNPs 9beta and Tth111I were not associated with semen parameters. Although the clinical impact of the findings is limited, the results substantiate a suggested link between stress and testicular function. Hence this investigation should be regarded as a discovery study generating hypotheses for future studies. PMID- 28992367 TI - Visualization of Peripheral Neuron Sensitization in a Surgical Mouse Model of Osteoarthritis by In Vivo Calcium Imaging. AB - OBJECTIVE: To develop a method for analyzing sensory neuron responses to mechanical stimuli in vivo, and to evaluate whether these neuronal responses change after destabilization of the medial meniscus (DMM). METHODS: DMM or sham surgery was performed in 10-week-old male C57BL/6 wild-type or Pirt-GCaMP3+/- mice. All experiments were performed 8 weeks after surgery. Knee and hind paw hyperalgesia were assessed in wild-type mice. The retrograde label DiI was injected into the ipsilateral knee to quantify the number of knee-innervating neurons in the L4 dorsal root ganglion (DRG) in wild-type mice. In vivo calcium imaging was performed on the ipsilateral L4 DRG of Pirt-GCaMP3+/- mice as mechanical stimuli (paw pinch, knee pinch, or knee twist) were applied to the ipsilateral hind limb. RESULTS: Eight weeks after surgery, mice subjected to DMM had more hyperalgesia in the knee and hind paw compared to mice subjected to sham surgery. Intraarticular injection of DiI labeled similar numbers of neurons in the L4 DRG of mice subjected to sham surgery and mice subjected to DMM. Increased numbers of sensory neurons responded to all 3 mechanical stimuli in mice subjected to DMM, as assessed by in vivo calcium imaging. The majority of responses in mice subjected to sham surgery and mice subjected to DMM were in small to medium-sized neurons, consistent with the size of nociceptors. The magnitude of responses was similar between mice subjected to sham surgery and mice subjected to DMM. CONCLUSION: Our findings indicate that increased numbers of small to medium-sized DRG neurons respond to mechanical stimuli 8 weeks after DMM surgery, suggesting that nociceptors have become sensitized by lowering the response threshold. PMID- 28992369 TI - Predictive value of pre-operative inflammation-based prognostic scores (neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and monocyte-to eosinophil ratio) in testicular sperm extraction: a pilot study. AB - To investigate the ability of some hematologic prognostic scores demonstrating inflammation in predicting sperm presence in testicular sperm extraction (TESE). We retrospectively investigated the medical data of 430 patients with the diagnosis of non-obstruc tive azoospermia (NOA) who had undergone TESE operation consecutively in our institution between the dates of January 2009 and February 2017. In all, 352 patients with the diagnosis of NOA, with bilaterally palpable vas deferens, who had undergone TESE for the first time, were included in the study. Patients with genetic anomalies, genital infection, history of surgery or vasectomy, chronic diseases, history of inflammatory, metabolic, rheumatologic, or malignant diseases, morbid obesity, with the diagnosis of clinical varicocele, or patients who had undergone TESE for the second time were excluded from the study. According to the results of TESE, the patients were divided into two groups as those with sperm retrieval and those without sperm retrieval. These groups were compared in terms of age, infertility duration, body mass index, hormone profile, hematologic parameters, neutrophil-to-lymphocyte ratio (NRL), monocyte-to-eosinophil ratio (MER), and platelet-to-lymphocyte ratio (PLR). The NLR and PLR levels were found to be significantly higher in patients without sperm retrieval at TESE compared to those with sperm retrieval. The logistic regression analysis showed NLR as an independent factor that showed the presence of spermatozoa at TESE (odds ratio: 4.786, %95 confidence interval: 2.667-8.589, p < 0.001). The area under the ROC curve (AUC) for the PLR was determined to be 0.574. As the calculated AUC value of the PLR was below 0.6, there was insufficient evidence determined at TESE to say that it was a reliable marker to indicate the presence of spermatozoa. The area of the MER value under the ROC curve was not statistically significant. It has been demonstrated that systemic inflammation negatively affects the probability of extracting spermatozoa in TESE and NLR is an independent factor indicating the presence of spermatozoa in TESE. PMID- 28992370 TI - Response to Afshar and Albrecht's (2017) Letter to the Editor. PMID- 28992371 TI - The impact of the omics era on the knowledge and use of Lysobacter species to control phytopathogenic micro-organisms. AB - Omics technologies have had a tremendous impact on underinvestigated genera of plant disease biocontrol agents such as Lysobacter. Strong evidence of the association between Lysobacter spp. and the rhizosphere has been obtained through culture-independent methods, which has also contributed towards highlighting the relationship between Lysobacter abundance and soil suppressiveness. It is conceivable that the role played by Lysobacter spp. in soil suppressiveness is related to their ability to produce an impressive array of lytic enzymes and antibiotics. Indeed, genomics has revealed that biocontrol Lysobacter strains share a vast number of genes involved in antagonism activities, and the molecular pathways underlying how Lysobacter spp. interact with the environment and other micro-organisms have been depicted through transcriptomic analysis. Furthermore, omics technologies shed light on the regulatory pathways governing cell motility and the biosynthesis of antibiotics. Overall, the results achieved so far through omics technologies confirm that the genus Lysobacter is a valuable source of novel biocontrol agents, paving the way for studies aimed at making their application in field conditions more reliable. PMID- 28992372 TI - The role of C4d deposition in the diagnosis of antibody-mediated rejection after lung transplantation. AB - Antibody-mediated rejection (AMR) is an increasingly recognized form of lung rejection. C4d deposition has been an inconsistent finding in previous reports and its role in the diagnosis has been controversial. We conducted a retrospective single-center study to characterize cases of C4d-negative probable AMR and to compare these to cases of definite (C4d-positive) AMR. We identified 73 cases of AMR: 28 (38%) were C4d-positive and 45 (62%) were C4d-negative. The two groups had a similar clinical presentation, and although more patients in the C4d-positive group had neutrophilic capillaritis (54% vs. 29%, P = .035), there was no significant difference in the presence of other histologic findings. Despite aggressive antibody-depleting therapy, 19 of 73 (26%) patients in the overall cohort died within 30 days, but there was no significant difference in freedom from chronic lung allograft dysfunction (CLAD) or survival between the two groups. We conclude that AMR may cause allograft failure, but that the diagnosis requires a multidisciplinary approach and a high index of suspicion. C4d deposition does not appear to be a necessary criterion for the diagnosis, and although some cases may respond initially to therapy, there is a high incidence of CLAD and poor survival after AMR. PMID- 28992373 TI - Variations in yield and gluten proteins in durum wheat varieties under late season foliar versus soil application of nitrogen fertilizer in a northern Mediterranean environment. AB - BACKGROUND: With the increasing demand for high-quality foodstuffs and concern for environmental sustainability, late-season nitrogen (N) foliar fertilization of common wheat is now an important and widespread practice. This study investigated the effects of late-season foliar versus soil N fertilization on yield and protein content of four varieties of durum wheat, Aureo, Ariosto, Biensur and Liberdur, in a three-year field trial in northern Italy. RESULTS: Variations in low-molecular-weight glutenins (LMW-GS), high-molecular-weight glutenins (HMW-GS) and gliadins were assessed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). It was found that N applied to the canopy did not improve protein rate compared with N application to the soil (general mean 138 mg g-1 ), but moderately increased productivity in the high yielding varieties Liberdur and Biensur (three-year means 7.23 vs 7.13 and 7.53 vs 7.09 t ha-1 respectively). Technological quality was mainly related to variety choice, Aureo and Ariosto having higher protein rates and glutenin/gliadin ratios. Also found was a strong 'variety * N application method' interaction in the proportions of protein subunits within each class, particularly LMW-GS and gliadins. A promising result was the higher N uptake efficiency, although as apparent balance, combined with higher HMW/LMW-GS ratio in var. Biensur. CONCLUSION: Late-season foliar N fertilization allows N fertilizer saving, potentially providing environmental benefits in the rainy climate of the northern Mediterranean area, and also leads to variety-dependent up-regulation of essential LMW-GS and gliadins. Variety choice is a key factor in obtaining high technological quality, although it is currently associated with modest grain yield. This study provides evidence of high quality in the specific high-yielding variety Biensur, suggesting its potential as a mono-varietal semolina for pasta production. (c) 2017 Society of Chemical Industry. PMID- 28992374 TI - Male accessory gland inflammation, infertility, and sexual dysfunctions: a practical approach to diagnosis and therapy. AB - The role of urogenital inflammation in causing infertility and sexual dysfunctions has long been a matter of debate in the international scientific literature. The most recent scientific evidences show that male accessory gland infection/inflammation could alter, with various mechanisms, both conventional and biofunctional sperm parameters, and determine worst reproductive outcome. At the same time, the high prevalence of erectile dysfunction and premature ejaculation in patients with male accessory gland infection/inflammation underlines the close link between these diseases and sexual dysfunctions. The aim of this review was to provide the reader the basis for a correct diagnosis of male accessory gland infection/inflammation and a subsequent appropriate therapeutic approach, particularly in patients with infertility and/or sexual dysfunction. PMID- 28992375 TI - Numerical Analysis of Groundwater Ridging Processes Considering Water-Air Flow in a Hillslope. AB - In this study, a water-air two-phase flow model was employed to investigate the formation, extension, and dissipation of groundwater ridging induced by recharge events in a hypothetical hillslope-riparian zone, considering interactions between the liquid and gas phases in soil voids. The simulation results show that, after a rain begins, the groundwater table near the stream is elevated instantaneously and significantly, thereby generating a pressure gradient driving water toward both the stream (the discharge of groundwater to the stream) and upslope (the extension of groundwater ridging into upslope). Meanwhile, the airflow upslope triggered by the advancing wetting front moves downward gradually. Therefore, the extension of groundwater ridging into upslope and the downward airflow interact within a certain region. After the rain stops, groundwater ridging near the stream declines quickly while the airflow in the lower part of upslope is still moving into the hillslope. Thus, the airflow upslope mitigates the dissipation of groundwater ridging. Additionally, the development of groundwater ridging under different conditions, including rain intensity, intrinsic permeability, capillary fringe height, and initial groundwater table, was analyzed. Changes in intrinsic permeability affect the magnitude of groundwater ridging near the stream, as well as the downward speed of airflow, thereby generating highly complex responses. The capillary fringe is not a controlling factor but an influence factor on the formation of groundwater ridging, which is mainly related to the antecedent moisture. It was demonstrated that groundwater ridging also occurs where an unsaturated zone occurs above the capillary fringe with a subsurface lateral flow. PMID- 28992376 TI - Technologies of cryoprotectant-free vitrification of human spermatozoa: asepticity as criterion of effectiveness. AB - This review describes 120 years history of technology for cryoprotectant-free cryopreservation of human spermatozoa by direct plunging into liquid nitrogen (vitrification). It is presented an explanation why cryoprotectant-free vitrification for some human ejaculates is better than conventional freezing and vitrification with the presence of cryoprotectants. Special attention is given to the extremely high viability of viruses, bacteria and micoplasmas after cryoprotectant-free cryopreservation in culture medium and even in distilled water. This fact increases the potential risk of disease transmission through liquid nitrogen. It is concretized the concept "asepticity" as obvious parameter for any medical assisted reproduction technology which includes the cooling of cells in liquid nitrogen. It is described the role of nonpermeable compounds of mediums for cryoprotectant-free vitrification: carbohydrates, proteins, lipoproteins, antioxidants. This review summarizes concerned data regarding two groups of different current technologies for cryoprotectant-free vitrification of human spermatozoa: with direct contact of spermatozoa with liquid nitrogen as well as with full isolation of these cells from liquid nitrogen (aseptic technologies). PMID- 28992378 TI - GREM2 nucleotide variants and the risk of tooth agenesis. AB - OBJECTIVE: The etiology of tooth agenesis (TA) is multifactorial and still not fully understood. The aim of the study was to test whether variants of GREM2, encoding a bone morphogenetic protein (BMP) antagonist, are associated with the risk of this common dental anomaly in a Polish population. SUBJECTS AND METHODS: Direct sequencing of the GREM2 coding sequence including exon/intron boundaries was performed in 95 patients with both hypodontia and oligodontia. All identified GREM2 variants were then further tested in an independent group of patients (n = 163) and controls (n = 184). RESULTS: The previously described, functional GREM2 mutation (c.226C > G, p.Gln76Glu) was identified in two patients with hypodontia and associated dental anomalies, including taurodontism and microdontia. This mutation generating an allele with increased inhibitory activity was not detected in the control group. The second identified GREM2 variant, c.-1-21C > T (rs11806449), was not associated with the risk TA. The polymorphism allele frequency in both patients and controls was 0.21 (OR = 1.0, 95%CI: 0.76-1.46). The rs11806449 did not correlate either with the overall TA phenotype or hypodontia/oligodontia phenotypes. CONCLUSION: Our study confirmed that GREM2 is a candidate gene for tooth agenesis, which mutations can explain, however, only a small fraction of the genetic contribution to the pathogenesis of this anomaly. PMID- 28992377 TI - A Single Session of Attentional Bias Modification Reduces Alcohol Craving and Implicit Measures of Alcohol Bias in Young Adult Drinkers. AB - BACKGROUND: Attentional bias modification (ABM) techniques for reducing problematic alcohol consumption hold promise as highly accessible and cost effective treatment approaches. A growing body of literature has examined ABM as a potentially efficacious intervention for reducing drinking and drinking-related cognitions in alcohol-dependent individuals as well as those at-risk of developing problem drinking habits. METHODS: This study tested the effectiveness of a single session of visual probe-based ABM training in a cohort of 60 non treatment-seeking young adult drinkers, with a focus on examining mechanisms underlying training efficacy. Participants were randomly assigned to a single session of active ABM training or a sham training condition in a laboratory setting. Measures of implicit drinking-related cognitions (alcohol Stroop and an Implicit Association Task) and attentional bias (AB; alcohol visual probe) were administered, and subjective alcohol craving was reported in response to in vivo alcohol cues. RESULTS: Results showed that active ABM training, relative to sham, resulted in significant differences in measures of implicit alcohol-related cognition, alcohol-related AB, and self-reports of alcohol craving. Mediation analysis showed that reductions in craving were fully mediated by ABM-related reductions in alcohol-Stroop interference scores, suggesting a previously undocumented relationship between the 2 measures. CONCLUSIONS: Results document the efficacy of brief ABM to reduce both implicit and explicit processes related to drinking, and highlight the potential intervention-relevance of alcohol related implicit cognitions in social drinkers. PMID- 28992380 TI - Outcomes of organ transplants when the donor is a prior recipient. AB - Organ shortage continues to challenge the field of transplantation. One potential group of donors are those who have been transplant recipients themselves, or Organ Donation After Transplant (ODAT) donors. We conducted a retrospective cohort study to describe ODAT donors and to compare outcomes of ODAT grafts versus conventional grafts. From October 1, 1987 to June 30, 2015, 517 former recipients successfully donated 803 organs for transplant. Former kidney recipients generally survived a median of approximately 4 years before becoming an ODAT donor whereas liver, lung, and heart recipients generally survived less than a month prior to donation. In the period June 1, 2005 to December 31, 2014, liver grafts from ODAT donors had a significantly higher risk of graft failure compared to non-ODAT liver transplants (P = .008). Kidney grafts donated by ODAT donors whose initial transplant occurred >1 year prior were associated with significantly increased graft failure (P = .012). Despite increased risk of graft failure amongst certain ODAT grafts, 5-year survival was still high. ODAT donors should be considered another form of expanded criteria donor under these circumstances. PMID- 28992379 TI - Association Between Anti-Citrullinated Fibrinogen Antibodies and Coronary Artery Disease in Rheumatoid Arthritis. AB - OBJECTIVE: Antibodies against citrullinated fibrinogen (anti-Cit-fibrinogen) have been implicated in rheumatoid arthritis (RA) and associated with cardiovascular risk in RA. The objective of this study was to examine the association between anti-Cit-fibrinogens and coronary artery disease (CAD) outcomes. METHODS: We performed the study in an RA cohort based in a large academic institution linked with electronic medical record data containing information on CAD outcomes from medical record review. Using a published bead-based assay method, we measured 10 types of anti-Cit-fibrinogens. We applied a score test to determine the association between the anti-Cit-fibrinogens as a group with CAD outcomes. Principal components analysis (PCA) was performed to assess whether the anti-Cit fibrinogens clustered into groups. Each group was then additionally tested for association with CAD. Sensitivity analyses were also performed using a published International Classification of Disease, Ninth Revision code group for ischemic heart disease (IHD) as the outcome. RESULTS: We studied 1,006 RA subjects (mean +/- SD age 61.0 +/- 13.0 years; 72.2% anti-cyclic citrullinated peptide positive). As a group, anti-Cit-fibrinogen was associated with CAD (P = 1.1 * 10 4 ). From the PCA analysis, we observed 3 main groups, of which only 1 group, containing 7 of the 10 anti-Cit-fibrinogens, was significantly associated with CAD outcomes (P = 0.015). In the sensitivity analysis, all anti-Cit-fibrinogens as a group remained significantly associated with IHD (P = 2.9 * 10-4 ). CONCLUSION: Anti-Cit-fibrinogen antibodies as a group were associated with CAD outcomes in our RA cohort, with the strongest signal for association arising from a subset of the autoantibodies. PMID- 28992381 TI - The self-sabotage of conservation: reply to Manfredo et al. PMID- 28992382 TI - Arterial Inflammation Detected With 18 F-Fluorodeoxyglucose-Positron Emission Tomography in Rheumatoid Arthritis. AB - OBJECTIVE: In addition to traditional risk factors, excess cardiovascular disease (CVD) in rheumatoid arthritis (RA) is attributed to enhanced vascular and/or systemic inflammation. In several small studies using 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG-PET/CT) to directly assess vascular inflammation, FDG uptake was higher in RA patients than in controls. Using a substantially larger sample of RA patients, we sought to identify RA disease characteristics independently associated with vascular FDG uptake. METHODS: RA patients underwent cardiac FDG-PET/CT, with aortic inflammation assessed by quantification of FDG uptake in the ascending aorta, calculated as the mean and maximum (max) standardized uptake value (SUV) of the entire ascending aorta and of its most diseased segment (SUV MDS). Univariate and multivariable regression models were constructed to model the associations of patient characteristics with aortic FDG uptake. RESULTS: Ninety-one RA patients were scanned. In multivariable models, in addition to the independent associations of hypertension and body mass index with increased aortic FDG uptake, the prevalence of rheumatoid nodules correlated with the SUV mean and SUV MDS mean measures, while anti-cyclic citrullinated peptide (anti-CCP) antibodies correlated inversely with these measures and with the SUV max and SUV MDS max (P < 0.05). A significant association of RA disease activity with aortic FDG uptake was observed but was restricted to anti-CCP seropositivity. CONCLUSION: Traditional CV risk factors and RA disease characteristics (rheumatoid nodules and the Disease Activity Score in 28 joints using the C-reactive protein level in anti-CCP antibody-positive individuals) were independently associated with ascending aortic FDG uptake in RA patients without clinical CVD. PMID- 28992383 TI - Evaluation of a Trauma-Focused Group Intervention for Unaccompanied Young Refugees: A Pilot Study. AB - Recent research has shown that unaccompanied young refugees (UYR) encounter a wide range of traumatic events during preflight, flight, and resettlement. Although many UYR are resourceful, many develop posttraumatic stress symptoms (PTSS). However, only a small number of vulnerable UYR have access to trauma focused interventions. Trauma-focused group interventions, adapted to the needs of UYR, may be one way of improving their mental health. A total of 29 male UYR between 14 and 18 years of age, mainly from Afghanistan, participated in the evaluation study of a trauma-focused group intervention entitled Mein Weg (My Way). The intervention included six sessions of psychoeducation, relaxation, trauma narrative, and cognitive restructuring. Pre-post comparisons of PTSS assessed by the Child and Adolescent Trauma Screen (CATS) were used. At study entry, participants endorsed, on average, eight traumatic events. After the group intervention, the participants reported significantly fewer overall PTSS preintervention mean = 27.6, SD = 7.9; postintervention mean = 20.7, SD = 6.3; t(28) = 4.2, p = .001, Cohen's d = 0.97. Improvement was especially pronounced in the domains of reexperiencing and avoidance, as well as negative alterations in cognitions and mood. There were 14 participants preintervention and 7 postintervention who fulfilled the PTSD criteria. This pilot study presented initial evidence of the efficacy of the trauma-focused group intervention with regard to PTSS reduction. PMID- 28992384 TI - Invited letter in response to "Predicted indirectly recognizable HLA epitopes (PIRCHE): Only the tip of the iceberg?" PMID- 28992385 TI - Synthesis of Mono- and Bis(fluoroalkyl)pyrimidines from FARs, Fluorinated Acetoacetates, and Malononitrile Provides Easy Access to Novel High-Value Pyrimidine Scaffolds. AB - A new strategy was developed using fluorinated acetoacetates, malononitrile, and fluoroalkyl amino reagents (FARs) to access unprecedented 4,6 bis(fluoroalkyl)pyrimidine-5-carboxylates, their carboxylic acid analogues, and 4 amino-6-(fluoroalkyl)pyrimidine-5-carbonitriles. An efficient cyclization step using suitable amidines was developed under microwave irradiation, providing the desired pyrimidines rapidly and efficiently. Standard saponification conditions were applied from carboxylate derivatives to access to the corresponding carboxylic acids. These new valuable building blocks, bearing either a single or two emergent fluorinated substituents, hold strong potential for medicinal and agrochemical research. PMID- 28992386 TI - Interaction Between the MU-Opioid Receptor Gene and the Number of Heavy-Drinking Peers on Alcohol Use. AB - BACKGROUND: The presence of heavy-drinking peers may trigger genetic vulnerabilities to alcohol use. Limited correlational findings, albeit mixed as a function of age, suggest that carriers of a MU-opioid receptor (OPRM1) G allele may be more vulnerable than noncarriers to alcohol-promoting perceived peer environments. However, research has not yet examined such genetic susceptibility to actual (rather than perceived) peer environments through an experimental, ad libitum alcohol administration design. This study examined whether OPRM1 modulates the effects of heavy-drinking group size on alcohol consumption and explored potential mediators of such OPRM1-based differences. METHODS: Caucasian young adult moderate to heavy drinkers (N = 116; mean age = 22 years [SD = 2.21], 49% female) were randomly assigned to consume alcohol in the presence of none, 1, or 3 heavy-drinking peer confederates. RESULTS: Results showed no significant moderating effects of OPRM1 in the relationship between the number (or presence) of heavy-drinking peers and voluntary alcohol consumption (partial eta2 = 0.01). This result remained the same after controlling for sex, age, and typical drinking quantity as well as their 2-way interactions with OPRM1 and social drinking condition. In addition, OPRM1 did not moderate the peer influence on any proposed mediating variables, including craving for alcohol and subjective responses to alcohol. CONCLUSIONS: Findings suggest no OPRM1-based susceptibility to the number of heavy-drinking peers, adding to the existing mixed findings from correlational studies. Future research on OPRM1-related susceptibility to alcohol promoting peer environments through meta-analytic synthesis and both experimental and prospective, multiwave designs is needed to resolve these mixed findings. PMID- 28992387 TI - Nationwide Experience With Off-Label Use of Interleukin-1 Targeting Treatment in Familial Mediterranean Fever Patients. AB - OBJECTIVE: Approximately 30-45% of patients with familial Mediterranean fever (FMF) have been reported to have attacks despite colchicine treatment. Currently, data on the treatment of colchicine-unresponsive or colchicine-intolerant FMF patients are limited; the most promising alternatives seem to be anti-interleukin 1 (anti-IL-1) agents. Here we report our experience with the off-label use of anti-IL-1 agents in a large group of FMF patients. METHODS: In all, 21 centers from different geographical regions of Turkey were included in the current study. The medical records of all FMF patients who had used anti-IL-1 treatment for at least 6 months were reviewed. RESULTS: In total, 172 FMF patients (83 [48%] female, mean age 36.2 years [range 18-68]) were included in the analysis; mean age at symptom onset was 12.6 years (range 1-48), and the mean colchicine dose was 1.7 mg/day (range 0.5-4.0). Of these patients, 151 were treated with anakinra and 21 with canakinumab. Anti-IL-1 treatment was used because of colchicine resistant disease in 84% and amyloidosis in 12% of subjects. During the mean 19.6 months of treatment (range 6-98), the yearly attack frequency was significantly reduced (from 16.8 to 2.4; P < 0.001), and 42.1% of colchicine-resistant FMF patients were attack free. Serum levels of C-reactive protein, erythrocyte sedimentation rate, and 24-hour urinary protein excretion (5,458.7 mg/24 hours before and 3,557.3 mg/24 hours after) were significantly reduced. CONCLUSION: Anti-IL-1 treatment is an effective alternative for controlling attacks and decreasing proteinuria in colchicine-resistant FMF patients. PMID- 28992389 TI - Characterizing Stream-Aquifer Exchanges with Self-Potential Measurements. AB - Characterizing the interactions between streams and aquifers is a major challenge in hydrology. Electrical self-potential (SP) is sensitive to groundwater flow through the electrokinetic effect, which is proportional to Darcy velocity. SP surveys have been extensively used for the characterization of seepage flow in a variety of contexts. But to our knowledge, a model coupling SP and groundwater flow has never been implemented for the study of stream-aquifer interactions. To address the issue, we first implemented a two-dimensional model to a synthetic stream-aquifer cross section. Results underline the very distinct nature of SP profiles in gaining or losing stream conditions. Second, we presented a field application in a transect crossing a stream in losing conditions. The coupled model successfully reproduced the observed SP profile. This inverse modeling of the SP signal provides quantitative data on hydrodynamic parameters (hydraulic conductivity, hydraulic heads) and geophysical parameters (coupling coefficient). Nevertheless, all relevant parameters cannot be uniquely estimated without precise prior information on at least some of these parameters. Our results confirm the potential of SP surveys on the characterization of stream-aquifer exchanges. Recommendations on the collection of high-quality data are also provided, along with a description of the contexts in which the methodology is likely to perform well. PMID- 28992388 TI - Impact of nutrition interventions on pediatric mortality and nutrition outcomes in humanitarian emergencies: A systematic review. AB - OBJECTIVES: Malnutrition contributes to paediatric morbidity and mortality in disasters and complex emergencies, but summary data describing specific nutritional interventions in these settings are lacking. This systematic review aimed to characterise such interventions and their effects on paediatric mortality, anthropometric measures and serum markers of nutrition. METHODS: A systematic search of OVID MEDLINE, Cochrane Library and relevant grey literature was conducted. We included all randomised controlled trials and observational controlled studies evaluating effectiveness of nutritional intervention(s) on defined health outcomes in children and adolescents (0-18 years) within a disaster or complex emergency. We extracted study characteristics, interventions and outcomes data. Study quality was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. RESULTS: A total of 31 studies met inclusion criteria. Most were conducted in Africa (17), during periods of conflict or hunger gaps (14), and evaluated micronutrient supplementation (14) or selective feeding (10). Overall study quality was low, with only two high and four moderate quality studies. High- and medium-quality studies demonstrated positive impact of fortified spreads, ready-to-use therapeutic foods, micronutrient supplementation, and food and cash transfers. CONCLUSION: In disasters and complex emergencies, high variability and low quality of controlled studies on paediatric malnutrition limit meaningful data aggregation. If existing research gaps are to be addressed, the inherent unpredictability of humanitarian emergencies and ethical considerations regarding controls may warrant a paradigm shift in what constitutes adequate methods. Periodic hunger gaps may offer a generalisable opportunity for robust trials, but consensus on meaningful nutritional endpoints is needed. PMID- 28992390 TI - Response of MG63 osteoblasts on bacterial challenge is dependent on the state of differentiation. AB - The present in vitro study examines molecular processes that are relevant during bone homeostasis after Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis infection with a focus on the differentiation level of osteoblasts. Regenerative processes are often hindered by the recurrence of bacterial infections, which can ultimately provoke a severe destruction of bone tissue. To obtain more detailed insights into such a complex scenario, we have used undifferentiated MG63 osteoblast-like cells as an experimental paradigm to examine the impact of two oral pathogens, A. actinomycetemcomitans and P. gingivalis, on proliferation, cytotoxicity and osteogenic differentiation. Cell culture experiments were performed to analyze cellular behavior. The level of genes interfering with bone tissue integrity (matrix metalloproteinases and their tissue inhibitors) and osteogenic markers (alkaline phosphatase, Runx2, human beta-defensin-2) was compared in undifferentiated versus differentiated MG63 cells using real-time polymerase chain reaction. Functional activity of matrix metalloproteinases was quantified by zymography. Western blot analysis was used to verify the phosphorylation state of mitogen-activated protein kinases p38 and extracellular-signal-regulated kinases 1/2. When co-cultured with undifferentiated MG63 cells, oral pathogens provoked distinct cellular effects. Only A. actinomycetemcomitans reduced cell proliferation, increased cell death, and induced osteogenic differentiation. A comparison of matrix metalloproteinase network stability in the presence of oral pathogens revealed a partial sensitivity towards P. gingivalis but not A. actinomycetemcomitans. So, beside the proof of concept that MG63 cells co-cultured with oral pathogens can serve as an in vitro model for mimicking destructive and regenerative events after bacterial infections, our data indicate that double infections might counterbalance otherwise positive effects. PMID- 28992392 TI - Norepinephrine infusion improves haemodynamics in the preterm infants during septic shock. AB - AIM: This study evaluated the clinical and haemodynamic effects of norepinephrine infusion in preterm infants. METHODS: The effects of norepinephrine therapy for refractory hypotension were evaluated in preterm infants between April 2009 and April 2011 at the neonatal intensive care unit of Sainte-Justine Hospital, Montreal, Quebec. Changes in haemodynamics and clinical parameters were analysed eight hours before and eight hours after the start of norepinephrine infusion, and eight hours after its cessation. RESULTS: During the study, 30 preterm infants at a mean gestational age of 26.5 +/- 2.6 weeks (median: 25.7, 23.4-34) and birthweight of 903 +/- 437 g (median 827, 450-2550) received norepinephrine infusion for neonatal septic shock. After eight hours of treatment, mean blood pressure, urine output and FiO2 significantly improved. Eight hours after cessation of norepinephrine infusion, the number of patients treated with other inotropes decreased significantly, 24 patients (80%) had normal mean blood pressure and 27 patients (90%) had normal urine output. CONCLUSION: Norepinephrine therapy could be considered to improve blood pressure and urine output during neonatal septic shock in preterm infants. Further studies are needed to prove the efficacy and safety of norepinephrine infusion in neonates. PMID- 28992391 TI - Four years of case-based surveillance of meningitis following the introduction of MenAfriVac in Moissala, Chad: lessons learned. AB - OBJECTIVE: Case-based surveillance of bacterial meningitis in sentinel districts has been recommended after the introduction of the conjugated vaccine against Neisseria meningitidis serogroup A (NmA), MenAfriVac, in the African meningitis belt. Here we report data and lessons learnt from four years of surveillance in the district of Moissala, Chad. METHODS: All suspected cases of meningitis were referred free of charge to the district hospital for lumbar puncture and treatment. Cerebrospinal fluid samples were tested with Pastorex latex agglutination in Moissala, and inoculated trans-isolate media were used for culture and PCR at the national reference laboratory and/or at the Norwegian Institute of Public Health. RESULTS: From July 2012 to December 2016, 237 suspected cases of meningitis were notified, and a specimen was collected from 224. Eighty-three samples were positive for a bacterial pathogen by culture, PCR or Pastorex, including 58 cases due to Streptococcus pneumoniae with only 28 of 49 pneumococcal meningitis confirmed by culture or PCR correctly identified by Pastorex. Four cases of NmA were detected by Pastorex, but none were confirmed by PCR. CONCLUSION: Implementation of case-based surveillance for meningitis is feasible in Chad, but has required political and technical engagement. Given the high proportion of S. pneumoniae and its poor detection by Pastorex, continued use of PCR is warranted for surveillance outside of outbreaks, and efforts to accelerate the introduction of pneumococcal conjugate vaccines are needed. Introduction of MenAfriVac in routine immunisation and future availability of a pentavalent meningococcal conjugate vaccine will be key elements for the sustained reduction in meningitis outbreaks in the area. PMID- 28992393 TI - "On-Droplet" Chemistry: The Cycloaddition of Diethyl Azodicarboxylate and Quadricyclane. AB - Sharpless and co-workers previously studied the [2sigma+2sigma+2pi] cycloaddition of diethyl azodicarboxylate (DEAD) and quadricyclane and reported that the addition of water to the neat reagents caused an acceleration in the reaction rate, giving birth to what has been called "on-water" chemistry. We have examined the same reaction in aqueous microdroplets (ca. 5 MUm diameter) and find that the cycloaddition reaction is accelerated even further (by a factor of 102 ) compared to that of the "on-water" reaction reported previously. The trends of acceleration in solvents other than water demonstrated by Sharpless and colleagues were replicated in the corresponding microdroplet experiments. We also find that DEAD reacts with itself to form a variety of hydrazine carboxylates and intercept intermediates of this reaction in microdroplets to validate a mechanism proposed herein. We suggest that "on-droplet" chemistry, similar to "on-water" chemistry, may be a general process of synthetic interest. PMID- 28992394 TI - Brief Report: Loss of Muscle Strength Prior to Knee Replacement: A Question of Anatomic Cross-Sectional Area or Specific Strength? AB - OBJECTIVE: To determine whether loss in thigh muscle strength prior to knee replacement is caused by reductions of muscle strength in the anatomic cross sectional area or by reductions of specific strength. METHODS: All 100 of the participants in the Osteoarthritis Initiative who underwent knee replacement and whose medical records included data on thigh isometric muscle strength and magnetic resonance imaging (MRI) (58 women, and 42 men, mean +/- SD age 65 +/- 8 years, mean +/- SD body mass index [BMI] 29 +/- 5 kg/m2 ) were matched with a control (no knee replacement) for age, sex, height, BMI, and radiographic severity. Thigh muscle anatomic cross-sectional area was determined by MRI at the research visit before knee replacement (time 0) and 2 years before time 0 (time 2). Specific strength (strength/anatomic cross-sectional area) was calculated, and the measures were compared by conditional logistic regression (i.e., odds ratio [OR] per standard deviation). ORs adjusted for pain (ORadj ) and 95% confidence intervals (95% CIs) were also calculated. RESULTS: Knee replacement cases had significantly smaller extensor (but not flexor) anatomic cross sectional areas than controls at time 0 (women, ORadj 1.89 [95% CI 1.05-3.90]; men, ORadj 2.22 [95% CI 1.04-4.76]), whereas no significant differences were found at time -2. Women who had knee replacement showed lower levels of extensor specific strength than controls at time 0 (OR 1.59 [95% CI 1.02-2.50]), although this difference was not observed in men and did not maintain significance after adjustment for pain (ORadj 1.22 [95% CI 0.71-2.08]). Female cases lost significantly more extensor specific strength between time -2 and time 0 than controls (ORadj 3.76 [95% CI 1.04-13.60]), whereas no significant differences were noted at time -2, or in men. CONCLUSION: Prior to knee replacement, a significant reduction in knee extensor strength appears to occur in women through 2 mechanisms: one driven by pain (loss of specific strength) and one independent of pain (loss of muscle anatomic cross-sectional area). Men who underwent knee replacement showed significantly reduced levels of extensor anatomic cross sectional area, but not significantly lower strength or specific strength. PMID- 28992395 TI - Changes in white matter microstructure predict lithium response in adolescents with bipolar disorder. AB - OBJECTIVES: To investigate whether response to lithium treatment in pediatric bipolar disorder can be predicted by changes in white matter microstructure in key cortico-limbic tracts involved in emotion regulation. METHODS: Eighteen clinically referred lithium-naive patients (mean age 15.5 years) were administered clinical rating scales and diffusion tensor imaging (DTI) examinations at baseline and following 4 weeks of lithium treatment. Clinical ratings were repeated following 8 weeks of treatment. Patients with Clinical Global Impressions (CGI) ratings of 1 ("very much improved") or 2 ("much improved") were classified as responders. Ten healthy volunteers received baseline and follow-up DTI examinations. Using the ENIGMA pipeline, we investigated the relationship between changes in fractional anisotropy (FA) in the cingulum hippocampus (CGH) and clinical response to lithium. RESULTS: Patients demonstrated significantly lower FA compared to healthy volunteers in the left and right CGH white matter at baseline. Following 4 weeks of lithium treatment, FA in the left CGH increased in patients, but no significant changes in FA were observed among the untreated healthy volunteers. Lithium responders had a significantly greater increase in FA compared to non-responders. Moreover, baseline (pre-treatment) FA in the left CGH white matter significantly predicted week 8 overall CGI severity score, with post hoc analyses indicating that these effects were evident for both severity of depression and mania. CONCLUSIONS: Our findings suggest that response to lithium treatment in pediatric bipolar disorder is associated with normalization of white matter microstructure in regions associated with emotion processing. PMID- 28992397 TI - Prognostic Significance of Cavitary Lung Nodules in Granulomatosis With Polyangiitis (Wegener's): A Clinical Imaging Study of 225 Patients. AB - OBJECTIVE: Granulomatosis with polyangiitis (Wegener's) (GPA) is a systemic necrotizing vasculitis in which pulmonary nodules are a common manifestation. Our study examined whether pulmonary nodules, and nodule type (solid versus cavitary), are associated with different disease manifestations and outcomes. METHODS: Demographic, clinical, biologic, and radiologic data at diagnosis and during followup and treatments of GPA patients followed at the Mount Sinai Hospital (Canada) Vasculitis Clinic were analyzed. Patients were separated by the absence of lung nodules, presence of solid nodules only, and presence of cavitary nodules (+/- solid nodules). The study outcomes included followup lung imaging, relapses, and deaths. RESULTS: Of 225 patients with GPA, 46 had solid nodules only and 44 had cavitary nodules at diagnosis. Demographic and clinical manifestations were similar in the patient subgroups at diagnosis. Cyclophosphamide (CYC) was used for induction after diagnosis in 76.7% of patients with cavitary nodules, compared with 64.7% of patients without nodules and 51.1% of patients with solid nodules (P = 0.04). The mean +/- SD followup after diagnosis was 106.6 +/- 92.6 months, and 6 of the patients died. In multivariable analysis, diagnosis before 2000 or pulmonary nodule cavitation at diagnosis were associated with relapse, with a hazard ratio of 0.38 (95% confidence interval [95% CI] 0.22-0.65; P < 0.001) and 1.53 (95% CI 1.00-2.33; P = 0.05), respectively, after adjustment for CYC use. CONCLUSION: The presence of cavitary nodules led to increased use of CYC but had no impact on survival. Relapse occurred more often, however, in patients with cavitary nodules than in those with solid nodules or no nodules, and should be studied in other cohorts. PMID- 28992398 TI - Impact of Social Cognition on Alcohol Dependence Treatment Outcome: Poorer Facial Emotion Recognition Predicts Relapse/Dropout. AB - BACKGROUND: Despite growing evidence for neurobehavioral deficits in social cognition in alcohol use disorder (AUD), the clinical relevance remains unclear, and little is known about its impact on treatment outcome. This study prospectively investigated the impact of neurocognitive social abilities at treatment onset on treatment completion. METHODS: Fifty-nine alcohol-dependent patients were assessed with measures of social cognition including 3 core components of empathy via paradigms measuring: (i) emotion recognition (the ability to recognize emotions via facial expression), (ii) emotional perspective taking, and (iii) affective responsiveness at the beginning of inpatient treatment for alcohol dependence. Subjective measures were also obtained, including estimates of task performance and a self-report measure of empathic abilities (Interpersonal Reactivity Index). According to treatment outcomes, patients were divided into a patient group with a regular treatment course (e.g., with planned discharge and without relapse during treatment) or an irregular treatment course (e.g., relapse and/or premature and unplanned termination of treatment, "dropout"). RESULTS: Compared with patients completing treatment in a regular fashion, patients with relapse and/or dropout of treatment had significantly poorer facial emotion recognition ability at treatment onset. Additional logistic regression analyses confirmed these results and identified poor emotion recognition performance as a significant predictor for relapse/dropout. Self-report (subjective) measures did not correspond with neurobehavioral social cognition measures, respectively objective task performance. Analyses of individual subtypes of facial emotions revealed poorer recognition particularly of disgust, anger, and no (neutral faces) emotion in patients with relapse/dropout. CONCLUSIONS: Social cognition in AUD is clinically relevant. Less successful treatment outcome was associated with poorer facial emotion recognition ability at the beginning of treatment. Impaired facial emotion recognition represents a neurocognitive risk factor that should be taken into account in alcohol dependence treatment. Treatments targeting the improvement of these social cognition deficits in AUD may offer a promising future approach. PMID- 28992400 TI - Letter to the Editor: Ding Q, Wang Z, Shen M, Su Z, and Shen L (2017) Acute Alcohol Exposure and Risk of Mortality of Patients with Traumatic Brain Injury: A Systematic Review and Meta-Analysis. PMID- 28992396 TI - Alcohol Feeding in Mice Promotes Colonic Hyperpermeability and Changes in Colonic Organoid Stem Cell Fate. AB - BACKGROUND: Alcohol increases intestinal permeability to proinflammatory microbial products that promote liver disease, even after a period of sobriety. We sought to test the hypothesis that alcohol affects intestinal stem cells using an in vivo model and ex vivo organoids generated from jejunum and colon from mice fed chronic alcohol. METHODS: Mice were fed a control or an alcohol diet. Intestinal permeability, liver steatosis-inflammation, and stool short-chain fatty acids (SCFAs) were measured. Jejunum and colonic organoids and tissue were stained for stem cell, cell lineage, and apical junction markers with assessment of mRNA by PCR and RNA-seq. ChIP-PCR analysis was carried out for Notch1 using an antibody specific for acetylated histone 3. RESULTS: Alcohol-fed mice exhibited colonic (but not small intestinal) hyperpermeability, steatohepatitis, and decreased butyrate/total SCFA ratio in stool. Stem cell, cell lineage, and apical junction marker staining in tissue or organoids from jejunum tissue were not impacted by alcohol. Only chromogranin A (Chga) was increased in jejunum organoids by qPCR. However, colonic tissue and organoid staining exhibited an alcohol-induced significant decrease in cytokeratin 20+ (Krt20+) absorptive lineage enterocytes, a decrease in occludin and E-cadherin apical junction proteins, an increase in Chga, and an increase in the Lgr5 stem cell marker. qPCR revealed an alcohol-induced decrease in colonic organoid and tissue Notch1, Hes1, and Krt20 and increased Chga, supporting an alteration in stem cell fate due to decreased Notch1 expression. Colonic tissue ChIP-PCR revealed alcohol feeding suppressed Notch1 mRNA expression (via deacetylation of histone H3) and decreased Notch1 tissue staining. CONCLUSIONS: Data support a model for alcohol-induced colonic hyperpermeability via epigenetic effects on Notch1, and thus Hes1, suppression through a mechanism involving histone H3 deacetylation at the Notch1 locus. This decreased enterocyte and increased enteroendocrine cell colonic stem cell fate and decreased apical junctional proteins leading to hyperpermeability. PMID- 28992399 TI - Comparison of the Lupus Foundation of America-Rapid Evaluation of Activity in Lupus to More Complex Disease Activity Instruments As Evaluated by Clinical Investigators or Real-World Clinicians. AB - OBJECTIVE: Lupus disease measures such as the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the British Isles Lupus Assessment Group (BILAG) index are challenging to interpret. The Lupus Foundation of America-Rapid Evaluation of Activity in Lupus (LFA-REAL) is intended to provide an efficient application of anchored visual analog scores, each representing the individual severity of active symptoms, with the sum of individual scores deriving an overall disease activity assessment. Our objective was to compare the performance of LFA-REAL to systemic lupus erythematosus disease activity assessments and compare scores between trained lupus clinical investigators and clinicians. METHODS: Investigators scored the SLEDAI, BILAG, physician's global assessment (PGA), and LFA-REAL, while the clinicians scored the LFA-REAL. The level of agreement between physicians and instruments was determined. RESULTS: The study included 99 patients (93% women, 31% white, mean +/- SD ages 43.4 +/- 13.2 years). At the first visit, the mean +/- SD SLEDAI score was 5.5 +/- 4.5, BILAG score 6.7 +/- 7.8, and PGA score 33.6 +/- 24.5. The mean +/- SD investigator LFA REAL score was 46.2 +/- 42.9, and clinician LFA-REAL score 56.1 +/- 53.6. At the second visit, the mean +/- SD investigator LFA-REAL score was 41.3 +/- 36.7, and clinician LFA-REAL score 48.3 +/- 42.6. Total LFA-REAL scores correlated positively with PGA, SLEDAI, and BILAG (rho = 0.58-0.88, P < 0.001). LFA-REAL scores produced correlation coefficients of rho > 0.7 for musculoskeletal, mucocutaneous, and renal BILAG domains. The intraclass correlation coefficient between the LFA-REAL scores of investigators and clinicians was 0.79 for visit 1 (P < 0.001) and 0.86 for visit 2 (P < 0.001). CONCLUSION: The LFA-REAL provides a reliable surrogate for more complicated disease activity measures when used by lupus clinical investigators or clinicians. PMID- 28992401 TI - Serum and sputum calprotectin, a reflection of neutrophilic airway inflammation in asthmatics after high-altitude exposure. PMID- 28992402 TI - Anomalous Polarized Raman Scattering and Large Circular Intensity Differential in Layered Triclinic ReS2. AB - The Raman tensor of a crystal is the derivative of its polarizability tensor and is dependent on the symmetries of the crystal and the Raman-active vibrational mode. The intensity of a particular mode is determined by the Raman selection rule, which involves the Raman tensor and the polarization configurations. For anisotropic two-dimensional (2D) layered crystals, polarized Raman scattering has been used to reveal the crystalline orientations. However, due to its complicated Raman tensors and optical birefringence, the polarized Raman scattering of triclinic 2D crystals has not been well studied yet. Herein, we report the anomalous polarized Raman scattering of 2D layered triclinic rhenium disulfide (ReS2) and show a large circular intensity differential (CID) of Raman scattering in ReS2 of different thicknesses. The origin of CID and the anomalous behavior in polarized Raman scattering were attributed to the appearance of nonzero off diagonal Raman tensor elements and the phase factor owing to optical birefringence. This can provide a method to identify the vertical orientation of triclinic layered materials. These findings may help to further understand the Raman scattering process in 2D materials of low symmetry and may indicate important applications in chiral recognition by using 2D materials. PMID- 28992403 TI - Wearable Fabrics with Self-Branched Bimetallic Layered Double Hydroxide Coaxial Nanostructures for Hybrid Supercapacitors. AB - We report a flexible battery-type electrode based on binder-free nickel cobalt layered double hydroxide nanosheets adhered to nickel cobalt layered double hydroxide nanoflake arrays on nickel fabric (NC LDH NFAs@NSs/Ni fabric) using facile and eco-friendly synthesis methods. Herein, we utilized discarded polyester fabric as a cost-effective substrate for in situ electroless deposition of Ni, which exhibited good flexibility, light weight, and high conductivity. Subsequently, the vertically aligned NC LDH NFAs were grown on Ni fabric by means of a hot-air oven-based method, and fluffy-like NC LDH NS branches are further decorated on NC LDH NFAs by a simple electrochemical deposition method. The as prepared core-shell-like nanoarchitectures improve the specific surface area and electrochemical activity, which provides the ideal pathways for electrolyte diffusion and charge transportation. When the electrochemical performance was tested in 1 M KOH aqueous solution, the core-shell-like NC LDH NFAs@NSs/Ni fabric electrode liberated a maximum areal capacity of 536.96 MUAh/cm2 at a current density of 2 mA/cm2 and excellent rate capability of 78.3% at 30 mA/cm2 (420.5 MUAh/cm2) with a good cycling stability. Moreover, a fabric-based hybrid supercapacitor (SC) was assembled, which achieves a stable operational potential window of 1.6 V, a large areal capacitance of 1147.23 mF/cm2 at 3 mA/cm2, and a high energy density of 0.392 mWh/cm2 at a power density of 2.353 mW/cm2. Utilizing such high energy storage abilities and flexible properties, the fabricated hybrid SC operated the wearable digital watch and electric motor fan for real-time applications. PMID- 28992404 TI - Trace Na2CO3 Addition to Limestone Inducing High-Capacity SO2 Capture. AB - Although the literature has reported enhanced indirect sulfation of limestone by adding Na2CO3, the amount of Na2CO3 additive required to achieve high CaO conversion is typically high (~4.0 mol %), which commonly results in adverse effects in fluidized-bed combustion boiler systems and increased cost of sorbents. In this work, we demonstrate for the first time that trace Na2CO3 (0.1 mol %) can significantly enhance the sulfate conversion of limestone. This enhanced sulfation is attributed to the increased surface area and optimized pore size distribution. The trace Na2CO3 additive splits the pores of the original sorbents peaking at ~70 nm into pores peaking at ~4 nm and ~140 nm due to the slight promotion of sintering. This well-developed pore structure results in a relatively high reactivity for sulfation. Thus, the Na2CO3 additive influences the sorbent reactivity in two ways: (1) at less than 0.5 mol %, tuning its pore structure; (2) at more than 0.5 mol %, promoting the product layer diffusion. We also find that trace amount of other metal salts, such as CaCl2 and NaCl, clearly enhance the sulfation of limestone. The strategy of enhancing limestone sulfation by the addition of trace amount of metal salts offers evident engineering and economic advantage. PMID- 28992405 TI - High-Strength Films Consisted of Oriented Chitosan Nanofibers for Guiding Cell Growth. AB - Chitosan has biocompatibility and biodegradability; however, the practical use of the bulk chitosan materials is hampered by its poor strength, which can not satisfy the mechanical property requirement of organs. Thus, the construction of highly strong chitosan-based materials has attracted much attention. Herein, the high strength nanofibrous hydrogels and films (CS-E) were fabricated from the chitosan solution in LiOH/KOH/urea aqueous system via a mild regenerating process. Under the mild condition (ethanol at low temperature) without the severe fluctuation in the system, the alkaline-urea shell around the chitosan chains was destroyed, and the naked chitosan molecules had sufficient time for the orderly arrangement in parallel manner to form relatively perfect nanofibers. The nanofibers physically cross-linked to form CS-E hydrogels, which could be easily oriented by drawing to achieve a maximum orientation index of 84%, supported by the scanning electron microscopy and two-dimensional wide-angle X-ray diffraction. The dried CS-E films could be bent and folded arbitrarily to various complex patterns and shapes. The oriented CS-E films displayed even ultrahigh tensile strength (282 MPa), which was 5.6* higher than the chitosan films prepared by the traditional acid dissolving method. The CS-E hydrogels possessed hierarchically porous structure, beneficial to the cell adhesion, transportation of nutrients, and removal of metabolic byproducts. The cell assay results demonstrated that the CS-E hydrogels were no cytotoxicity, and osteoblastic cells could adhere, spread, and proliferate well on their surface. Furthermore, the oriented CS-E hydrogels could regulate the directional growth of osteoblastic cells along the orientation direction, on the basis of the filopodia of the cells to extend and adhere on the nanofibers. This work provided a novel approach to construct the oriented high strength chitosan hydrogels and films. PMID- 28992406 TI - Constructing an Anisotropic Triple-Pass Tubular Framework within a Lyophilized Porous Gelatin Scaffold Using Dexamethasone-Loaded Functionalized Whatman Paper To Reinforce Its Mechanical Strength and Promote Osteogenesis. AB - In bone tissue engineering (BTE), most of the currently developed scaffolds still lack the ability to demonstrate high porosity and high mechanical strength simultaneously or the ability to maintain bioactivity and sustained release of loaded biofactors. In this work, we constructed an anisotropic triple-pass tubular framework within a lyophilized porous GEL scaffold using FP, which was prepared by coating DEX-covered Whatman paper (WP) using the silk fibroin (SF) membrane with beta-sheet conformation. This novel structural design endowed the functionalized paper frame (FPF)/scaffold implant high porosity, high mechanical strength, and sustained DEX delivery capability. Specifically, its porosity was as high as 88.2%, approximating that of human cancellous bone. The pore diameters of the implant ranged from 50 to 350 MUm with an average pore diameter of 127.7 MUm, indicating proper pore sizes for successful diffusion of essential nutrients/oxygen and bone tissue-ingrowth. Owing to the construction of double network-like structure, the FPF/scaffold implant demonstrated excellent mechanical properties both in dry (174.7 MPa in elastic modulus and 14.9 MPa in compressive modulus) and wet states (59.0 MPa in elastic modulus and 3.3 MPa in compressive modulus), indicating its feasibility for in vivo implantation. Besides, the FPF/scaffold implant exhibited long-term DEX releasing behavior (over 50 days) with constant release rate in phosphate buffered saline (PBS). Murine osteoblasts MC3T3-E1 cultured in the porous FPF/scaffold implant had excellent viability. Furthermore, the cells cocultured with the FPF/scaffold implant showed positive proliferation, osteogenic differentiation, and calcium deposition. Twenty-eight days after implantation, extensive osteogenesis was observed in the rats treated with the FPF/scaffold implants. The anisotropic triple-pass tubular framework of the FPF/scaffold implant demonstrates structural similarities to the long bone. Therefore, this novel FPF/scaffold implant could be a better alternative for long bone defect repair. PMID- 28992408 TI - Analysis and Sensory Evaluation of Volatile Constituents of Fresh Blackcurrant (Ribes nigrum L.) Fruits. AB - Volatile constituents of fresh blackcurrant (Ribes nigrum L.) berries were isolated via vacuum-headspace extraction and analyzed by capillary gas chromatography-mass spectrometry. In agreement with previous studies with frozen fruits, short-chain esters and terpenes were major compound classes. However, rather high concentrations of C6-compounds (e.g., (E)-hex-2-enal, (Z)-hex-3-enal) constituted a striking difference to data reported for frozen fruits. Frozen storage of blackcurrant berries was shown to result in drastically reduced concentrations of C6-compounds and a shift of the volatile profile in favor of terpenes. The time-dependent enzymatic formation and isomerization of C6 compounds adds an additional element of variability to the spectrum of fresh blackcurrant volatiles. Nevertheless, blackcurrant cultivars can be classified according to the major classes of the volatiles of the fresh fruits, if prerequisites, such as the same growing location and the same state of ripeness, are met. The sensory contributions of volatiles of blackcurrant berries were assessed by gas chromatography-olfactometry in combination with aroma extract dilution analysis. 4-Methoxy-2-methyl-2-butanethiol, (Z)-3-hexenal, ethyl butanoate, 1,8-cineole, oct-1-en-3-one, and alkyl-substituted 3-methoxypyrazines were among the volatiles showing the highest aroma activity values. PMID- 28992407 TI - Perfluoroarene-Based Peptide Macrocycles to Enhance Penetration Across the Blood Brain Barrier. AB - Here we describe the utility of peptide macrocyclization through perfluoroaryl cysteine SNAr chemistry to improve the ability of peptides to cross the blood brain barrier. Multiple macrocyclic analogues of the peptide transportan-10 were investigated that displayed increased uptake in two different cell lines and improved proteolytic stability. One of these analogues (M13) exhibited substantially increased delivery across a cellular spheroid model of the blood brain barrier. Through ex vivo imaging of mouse brains, we demonstrated that this perfluoroarene-based macrocycle of TP10 exhibits increased penetration of the brain parenchyma following intravenous administration in mice. Finally, we evaluated macrocyclic analogues of the BH3 domain of the BIM protein to assess if our approach would be applicable to a peptide of therapeutic interest. We identified a BIM BH3 analogue that showed increased penetration of the brain tissue in mice. PMID- 28992409 TI - Hypoxia-Targeting, Tumor Microenvironment Responsive Nanocluster Bomb for Radical Enhanced Radiotherapy. AB - Although ultrasmall metal nanoparticles (NPs) have been used as radiosensitizers to enhance the local damage to tumor tissues while reducing injury to the surrounding organs, their rapid clearance from the circulatory system and the presence of hypoxia within the tumor continue to hamper their further application in radiotherapy (RT). In this study, we report a size tunable nanocluster bomb with a initial size of approximately 33 nm featuring a long half-life during blood circulation and destructed to release small hypoxia microenvironment targeting NPs (~5 nm) to achieve deep tumor penetration. Hypoxic profiles of solid tumors were precisely imaged using NP-enhanced computed tomography (CT) with higher spatial resolution. Once irradiated with a 1064 nm laser, CT-guided, local photothermal ablation of the tumor and production of radical species could be achieved simultaneously. The induced radical species alleviated the hypoxia induced resistance and sensitized the tumor to the killing efficacy of radiation in Akt-mTOR pathway-dependent manner. The therapeutic outcome was assessed in animal models of orthotopical breast cancer and pancreatic cancer, supporting the feasibility of our combinational treatment in hypoxic tumor management. PMID- 28992410 TI - Product Release Mechanism Associated with Structural Changes in Monomeric l Threonine 3-Dehydrogenase. AB - A short chain dehydrogenase like l-threonine 3-dehydrogenase (SDR-TDH) from metagenome data (mtTDH) was identified by database mining. Its enzymatic properties suggested that mtTDH has unique characteristics relative to other SDR TDHs, including two mesophilic and thermophilic SDR-TDHs identified in this study. The activation energy of mtTDH was the lowest (29.6 kJ/mol) of those of the SDR-TDHs, indicating that it is a psychrophilic enzyme. Size-exclusion chromatography analysis revealed mtTDH is a monomer. Crystal structures of mtTDH in apo, binary, and two ternary complexes (l-Ser- and l-Thr-soaked forms) were determined at resolutions of 1.25-1.9 A. Structural and computational analysis revealed the molecular mechanism of switching between the open and closed states induced by substrate binding and product release. Furthermore, six residues and two water molecules at the active site contributing to product release were assigned. The residues could be categorized into two groups on the basis of the enzymatic properties of their variants: S111, Y136, and T177 and S74, T178, and D179. The former group appeared to affect l-Thr dehydrogenation directly, because the kcat value of their variants was >80-fold lower than that of wild-type mtTDH. On the other hand, the latter group contributes to switching between the open and closed states, which is important for the high substrate specificity of SDR-TDH for l-Thr: the kcat and Km toward l-Thr values of variants in these residues could not be determined because the initial velocity was unsaturated at high concentrations of l-Thr. On the basis of these findings, we proposed a product release mechanism for SDR-TDH associated with specific structural changes. PMID- 28992411 TI - Genome Editing: Insights from Chemical Biology to Support Safe and Transformative Therapeutic Applications. AB - Programmable nuclease-based genome editing technologies, including the clustered, regularly interspaced, short palindromic repeats (CRISPR)/Cas9 system, are becoming an essential component of many applications ranging from agriculture to medicine. However, fundamental limitations currently prevent the widespread, safe, and practical use of genome editors, especially for human disease interventions. These limitations include off-target effects, a lack of control over editing activity, suboptimal DNA repair outcomes, insufficient target conversion, and inadequate delivery performance. This perspective focuses on the potential for biological chemistry to address these limitations such that newly developed genome editing technologies can enable the broadest range of potential future applications. Equally important will be the development of these powerful technologies within a relevant ethical framework that emphasizes safety and responsible innovation. PMID- 28992412 TI - Protein Science by DNA Sequencing: How Advances in Molecular Biology Are Accelerating Biochemistry. AB - A fundamental goal of protein biochemistry is to determine the sequence-function relationship, but the vastness of sequence space makes comprehensive evaluation of this landscape difficult. However, advances in DNA synthesis and sequencing now allow researchers to assess the functional impact of every single mutation in many proteins, but challenges remain in library construction and the development of general assays applicable to a diverse range of protein functions. This Perspective briefly outlines the technical innovations in DNA manipulation that allow massively parallel protein biochemistry and then summarizes the methods currently available for library construction and the functional assays of protein variants. Areas in need of future innovation are highlighted with a particular focus on assay development and the use of computational analysis with machine learning to effectively traverse the sequence-function landscape. Finally, applications in the fundamentals of protein biochemistry, disease prediction, and protein engineering are presented. PMID- 28992413 TI - Phenotypic Optimization of Urea-Thiophene Carboxamides To Yield Potent, Well Tolerated, and Orally Active Protective Agents against Aminoglycoside-Induced Hearing Loss. AB - Hearing loss is a major public health concern with no pharmaceutical intervention for hearing protection or restoration. Using zebrafish neuromast hair cells, a robust model for mammalian auditory and vestibular hair cells, we identified a urea-thiophene carboxamide, 1 (ORC-001), as protective against aminoglycoside antibiotic (AGA)-induced hair cell death. The 50% protection (HC50) concentration conferred by 1 is 3.2 MUM with protection against 200 MUM neomycin approaching 100%. Compound 1 was sufficiently safe and drug-like to validate otoprotection in an in vivo rat hearing loss model. We explored the structure-activity relationship (SAR) of this compound series to improve otoprotective potency, improve pharmacokinetic properties and eliminate off-target activity. We present the optimization of 1 to yield 90 (ORC-13661). Compound 90 protects mechanosensory hair cells with HC50 of 120 nM and demonstrates 100% protection in the zebrafish assay and superior physiochemical, pharmacokinetic, and toxicologic properties, as well as complete in vivo protection in rats. PMID- 28992414 TI - Synthesis of Spirolactams and Fused Bicyclic Lactams via Acid-Promoted Cyclolactamization of (Ethynyl(tosyl)amino)methyl-Tethered Cyclohex-2-enols. AB - A simple synthetic method to construct the spirolactam framework from TfOH catalyzed spirolactamization of cyclohex-2-enols bearing a tethered (arylethynyl(tosyl)amino)methyl moiety is described. The reaction proceeded through a keteniminium-allylic carbocation intermediate. Hydration of the keteniminium ion, followed by attack of the resulting enolate onto the tethered allylic carbocation, provided the spirolactam ring skeleton. This strategy could also be employed in the synthesis of fused bicyclic lactams from BF3.OEt2 assisted cyclolactamization of TBS-protected 2 (ethynyl(tosyl)amino)methylcyclohex-2-enols. PMID- 28992416 TI - Evaluation and Optimization of Interface Force Fields for Water on Gold Surfaces. AB - The structure and dynamics of water at gold surfaces are important for a variety of applications, including lab on a chip and electrowetting. Classical molecular dynamics (MD) simulations are frequently used to investigate systems with water gold interfaces, such as biomacromolecules in gold nanoparticle dispersions, but the accuracy of the simulations depends on the suitability of the force field. Density functional theory (DFT) calculations of a water molecule on gold were used as a benchmark to assess force field accuracy. It was found that Lennard Jones potentials did not reproduce the DFT water-gold configurational energy landscape, whereas the softer Morse and Buckingham potentials allowed for a more accurate representation. MD simulations with different force fields exhibited rather different structural and dynamic properties of water on a gold surface. This emphasizes the need for experimental data and further effort on the validation of a realistic force field for water-gold interactions. PMID- 28992415 TI - Weakly Trapped, Charged, and Free Excitons in Single-Layer MoS2 in the Presence of Defects, Strain, and Charged Impurities. AB - Few- and single-layer MoS2 host substantial densities of defects. They are thought to influence the doping level, the crystal structure, and the binding of electron-hole pairs. We disentangle the concomitant spectroscopic expression of all three effects and identify to what extent they are intrinsic to the material or extrinsic to it, i.e., related to its local environment. We do so by using different sources of MoS2-a natural one and one prepared at high pressure and high temperature-and different substrates bringing varying amounts of charged impurities and by separating the contributions of internal strain and doping in Raman spectra. Photoluminescence unveils various optically active excitonic complexes. We discover a defect-bound state having a low binding energy of 20 meV that does not appear sensitive to strain and doping, unlike charged excitons. Conversely, the defect does not significantly dope or strain MoS2. Scanning tunneling microscopy and density functional theory simulations point to substitutional atoms, presumably individual nitrogen atoms at the sulfur site. Our work shows the way to a systematic understanding of the effect of external and internal fields on the optical properties of two-dimensional materials. PMID- 28992417 TI - Smart Antibacterial Surfaces with Switchable Bacteria-Killing and Bacteria Releasing Capabilities. AB - The attachment and subsequent colonization of bacteria on the surfaces of synthetic materials and devices lead to serious problems in both human healthcare and industrial applications. Therefore, antibacterial surfaces that can prevent bacterial attachment and biofilm formation have been a long-standing focus of considerable interest and research efforts. Recently, a promising "kill-release" strategy has been proposed and applied to construct so-called smart antibacterial surfaces, which can kill bacteria attached to their surface and then undergo on demand release of the dead bacteria and other debris to reveal a clean surface under an appropriate stimulus, thereby maintaining effective long-term antibacterial activity. This Review focuses on the recent progress (particularly over the past 5 years) on such smart antibacterial surfaces. According to the different design strategies, these surfaces can be divided into three categories: (i) "K + R"-type surfaces, which have both a killing unit and a releasing unit; (ii) "K -> R"-type surfaces, which have a surface-immobilized killing unit that can be switched to perform a releasing function; and (iii) "K + (R)"-type surfaces, which have only a killing unit but can release dead bacteria upon the addition of a release solution. In the end, a brief perspective on future research directions and the major challenges in this promising field is also presented. PMID- 28992418 TI - Nitrogen Fixation via a Terminal Fe(IV) Nitride. AB - Terminal iron nitrides (Fe=N) have been proposed as intermediates of (bio)catalytic nitrogen fixation, yet experimental evidence to support this hypothesis has been lacking. In particular, no prior synthetic examples of terminal Fe=N species have been derived from N2. Here we show that a nitrogen fixing Fe-N2 catalyst can be protonated to form a neutral Fe(NNH2) hydrazido(2-) intermediate, which, upon further protonation, heterolytically cleaves the N-N bond to release [FeIV=N]+ and NH3. These observations provide direct evidence for the viability of a Chatt-type (distal) mechanism for Fe-mediated N2-to-NH3 conversion. The physical oxidation state range of the Fe complexes in this transformation is buffered by covalency with the ligand, a feature of possible relevance to catalyst design in synthetic and natural systems that facilitate multiproton/multielectron redox processes. PMID- 28992419 TI - Solution-Processed Ultrathin TiO2 Compact Layer Hybridized with Mesoporous TiO2 for High-Performance Perovskite Solar Cells. AB - The electron transport layer (ETL) is a key component of perovskite solar cells (PSCs) and must provide efficient electron extraction and collection while minimizing the charge recombination at interfaces in order to ensure high performance. Conventional bilayered TiO2 ETLs fabricated by depositing compact TiO2 (c-TiO2) and mesoporous TiO2 (mp-TiO2) in sequence exhibit resistive losses due to the contact resistance at the c-TiO2/mp-TiO2 interface and the series resistance arising from the intrinsically low conductivity of TiO2. Herein, to minimize such resistive losses, we developed a novel ETL consisting of an ultrathin c-TiO2 layer hybridized with mp-TiO2, which is fabricated by performing one-step spin-coating of a mp-TiO2 solution containing a small amount of titanium diisopropoxide bis(acetylacetonate) (TAA). By using electron microscopies and elemental mapping analysis, we establish that the optimal concentration of TAA produces an ultrathin blocking layer with a thickness of ~3 nm and ensures that the mp-TiO2 layer has a suitable porosity for efficient perovskite infiltration. We compare PSCs based on mesoscopic ETLs with and without compact layers to determine the role of the hole-blocking layer in their performances. The hybrid ETLs exhibit enhanced electron extraction and reduced charge recombination, resulting in better photovoltaic performances and reduced hysteresis of PSCs compared to those with conventional bilayered ETLs. PMID- 28992420 TI - Improved Chondrotoxic Profile of Liposomal Bupivacaine Compared With Standard Bupivacaine After Intra-articular Infiltration in a Porcine Model. AB - BACKGROUND: Increasingly, liposomal bupivacaine is being used with multimodal pain management strategies. In vitro investigations have shown decreased chondrotoxicity profiles for liposomal bupivacaine; however, there is no evidence regarding its in vivo effects. Hypothesis/Purpose: This study sought to investigate the in vivo chondrotoxicity of liposomal bupivacaine, hypothesizing that there would be increased chondrocyte viability after exposure to liposomal bupivacaine when compared with standard bupivacaine. STUDY DESIGN: Controlled laboratory study. METHODS: Eight juvenile, female Yorkshire cross piglets underwent a lateral stifle joint injection with either 1.3% liposomal bupivacaine or 0.5% bupivacaine. Injections were performed on one joint per animal with no injection to the contralateral knee, which served as the control. Chondrocyte viability was assessed 1 week after injection with a live-dead staining protocol and histologic examination. RESULTS: Significant chondrocyte death was seen with the live-dead staining in the bupivacaine group (33% nonviable cells) in comparison with liposomal bupivacaine (6.2%) and control (5.8%) groups ( P < .01). However, histologic examination showed no differences in chondral surface integrity, fibrillation, and chondrocyte viability. CONCLUSION: Liposomal bupivacaine was found to be safe for intra-articular injection in this animal model. Although bupivacaine demonstrated decreased chondrocyte viability on a cellular level, histologically there were no changes. This study highlights the dichotomy between fluorescent staining and histologic appearance of articular chondrocytes in short-term analyses of viability. CLINICAL RELEVANCE: This study supports the peri-articular application of liposomal bupivacaine in the setting of preserved articular cartilage. A single injection of standard bupivacaine did not produce histologic changes in the articular cartilage. PMID- 28992421 TI - Functional Hypoxia in Insects: Definition, Assessment, and Consequences for Physiology, Ecology, and Evolution. AB - Insects can experience functional hypoxia, a situation in which O2 supply is inadequate to meet oxygen demand. Assessing when functional hypoxia occurs is complex, because responses are graded, age and tissue dependent, and compensatory. Here, we compare information gained from metabolomics and transcriptional approaches and by manipulation of the partial pressure of oxygen. Functional hypoxia produces graded damage, including damaged macromolecules and inflammation. Insects respond by compensatory physiological and morphological changes in the tracheal system, metabolic reorganization, and suppression of activity, feeding, and growth. There is evidence for functional hypoxia in eggs, near the end of juvenile instars, and during molting. Functional hypoxia is more likely in species with lower O2 availability or transport capacities and when O2 need is great. Functional hypoxia occurs normally during insect development and is a factor in mediating life-history trade-offs. PMID- 28992422 TI - Confidence intervals for the common intraclass correlation in the analysis of clustered binary responses. AB - In cluster randomized trials, it is often of interest to estimate the common intraclass correlation at the design stage for sample size and power calculations, which are greatly affected by the value of a common intraclass correlation. In this article, we construct confidence intervals (CIs) for the common intraclass correlation coefficient of several treatment groups. We consider the profile likelihood (PL)-based approach using the beta-binomial models and the approach based on the concept of generalized pivots using the ANOVA estimator and its asymptotic variance. We compare both approaches with a number of large sample procedures as well as both parametric and nonparametric bootstrap procedures in terms of coverage and expected CI length through a simulation study, and illustrate the methodology with two examples from biomedical fields. The results support the use of the PL-based CI as it holds the preassigned confidence level very well and overall gives a very competitive length. PMID- 28992423 TI - Housekeeping and tissue-specific cis-regulatory elements: Recipes for specificity and recipes for activity. AB - Cell type-specific and housekeeping enhancers and promoters collectively control the transcriptional output of mammalian cells. Recent data clarify how DNA sequence features on the one hand control functional coupling of promoters with selected enhancers, and on the other impart high level of activity to a broad range of regulatory elements. PMID- 28992425 TI - Statistical planning in confirmatory clinical trials with multiple treatment groups, multiple visits, and multiple endpoints. AB - Multiplicity issues can be multidimensional: A confirmatory clinical trial may be designed to have efficacy assessed with two or more primary endpoints, for multiple dose groups, and at several post-baseline visits. Controlling for multiplicity in this situation is challenging because there can be a hierarchy with respect to some but not all measurements. If the higher dose is considered more efficacious, multiplicity approach may evaluate the higher dose with higher priority through a fixed sequential testing framework for dose assessments in combination with a Hochberg approach for endpoints. The lower dose is only assessed when the higher dose has significant results, which reduces the power for detecting signals in the lower dose group. However, in some instances the higher dose may associate with tolerability or safety concerns that preclude regulatory approval. A real confirmatory clinical trial with such challenges is provided as an illustrative example. We discuss closed testing procedures based on multi-way averages of comparisons for this complex multiplicity situation through illustrative case analyses and a simulation study. Such strategies manage the higher dose and the lower dose with equal priority, and they enable evaluation of the multiple endpoints at multiple visits collectively with power being reasonably high. PMID- 28992424 TI - Long-Term Outcome of Intravitreal Bevacizumab Followed by Ahmed Valve Implantation in the Management of Neovascular Glaucoma. AB - BACKGROUND: To report the outcome of intravitreal Bevacizumab followed by Ahmed valve implantation in the management of neovascular glaucoma in a patient group with extended follow-up. METHODS: The records of 16 patients (18 eyes) with neovascular glaucoma refractory to medical therapy who presented to a single surgeon between 2006-2008 were reviewed. Patients received pan-retinal photocoagulation and then intravitreal Bevacizumab followed by Ahmed valve implantation. The main outcome measures were: control of IOP (with or without additional medication), visual acuity (VA) and failure (IOP >21 mmHg or <6 mmHg, reoperation for glaucoma, or loss of light perception). RESULTS: Pre-operatively, all patients received pan-retinal photocoagulation followed by IVB at a mean of 15.9 (range 4-60) days prior to AGV. The mean pre-operative IOP was 37.1 mmHg (+/ 13.4) on 3.2 (+/-0.87) medications. Of the 18 eyes, 14 eyes (78%) were treated with AGV alone and 4 eyes (22%) with AGV combined with cataract extraction. Sixteen eyes (89%) received mitomycin C treatment intraoperatively. Post operatively, the mean follow-up period was 63 months (24-84). At final follow-up, the success rate was 50% (33.3% complete, 16.7% qualified) with a mean IOP of 18.1 mmHg (+/-9.5) on a mean number of 1.5 (+/-1.6) medications. The failure rate was 50%, with five eyes (27.8%) not meeting the IOP criteria for success (of these, three eyes required additional surgery to lower the IOP) and five eyes (22.2%) lost light perception. CONCLUSION: Intravitreal Bevacizumab followed by AGV offers long-term control of IOP without additional surgical intervention in the majority of cases. PMID- 28992426 TI - Predictors of Poor Clinical Outcome After Arthroscopic Labral Preservation, Capsular Plication, and Cam Osteoplasty in the Setting of Borderline Hip Dysplasia. AB - BACKGROUND: Borderline developmental dysplasia of the hip (BDDH) is frequently diagnosed concurrently with cam impingement. While hip arthroscopy has advanced the treatment of hip joint pathology, including femoroacetabular impingement (FAI), arthroscopic treatment for FAI in the setting of BDDH remains a challenge amid a subset of patients. The risk factors of poor clinical results after hip arthroscopic labral preservation and FAI corrections in the setting of BDDH patients have not been well established. HYPOTHESIS: Pre- and intraoperative findings can predict the poor clinical outcomes after hip arthroscopic surgery for FAI in the setting of BDDH. STUDY DESIGN: Case control study; Level of evidence, 3. METHODS: Of patients with BDDH (defined as lateral center edge [LCE] angle between 20 degrees and 25 degrees ) who underwent arthroscopic procedures for FAI between 2009 and 2014, 45 met inclusion criteria (45 hips: 15 males and 30 females). Their mean age was 31.4 years (range, 12-65 years), and the mean LCE angle was 23.2 degrees . Clinical and radiographic follow-up evaluations up to a minimum of 2 years after surgery were performed for all patients. Failure of the procedure was defined as conversion to subsequent surgery or having a Tonnis osteoarthritis grade of 2, and success was defined as patients who did not need subsequent surgery. Univariate analysis and Cox hazard proportional analysis were performed for both cohorts. RESULTS: Of 45 patients, 11 (24%) had revision surgery (endoscopic shelf acetabuloplasty for 5 patients, total hip arthroplasty for 2, and revision hip arthroscopy for 2) or advanced to Tonnis grade >=2 osteoarthritis and thus constituted the failure group. In the success group, modified Harris Hip Score (median, pre- vs postoperative: 72.1 vs 100, P< .001, Wilcoxon signed-rank test) and nonarthritic hip score (58.8 vs 98.8, P< .001) were significantly improved at the minimum 2-year follow-up. The median age of the failure group was significantly higher than that of the success group (47.0 vs 20.0, P< .001, Mann-Whitney Utest). Risk factors of poor clinical outcomes were identified as follows: age >=42 years (hazard ratio [HR], 11.6; 95% CI, 2.5 53.9; P= .002, Cox hazard model), broken Shenton line (HR, 6.4; 95% CI, 1.9-22.3; P= .003), Tonnis angle >=15 degrees (HR, 3.9; 95% CI, 1.2-12.9; P= .03), vertical center anterior (VCA) angle <=17 degrees (HR, 5.0; 95% CI, 1.5-17.1; P= .01), Tonnis grade 1 at preoperative radiograph (HR, 3.6; 95% CI, 1.1-11.7; P= .04), severe cartilage delamination at acetabulum (HR, 11.8; 95% CI, 3.0-46.1; P< .001), and mild cartilage damage at femoral head (HR, 8.1; 95% CI, 2.1-30.8; P= .002). CONCLUSION: Preoperative predictors of poorer outcomes from hip arthroscopic labral preservation, capsular plication, and cam osteoplasty in the setting of BDDH are age >=42 years old, broken Shenton line, osteoarthritis, Tonnis angle >=15 degrees , and VCA angle <=17 degrees on preoperative radiographs. Intraoperative predictors of poorer outcomes are severe acetabular chondral damage and even mild femoral chondral damage. Although the patients in the setting of BDDH may have good outcomes from isolated hip arthroscopy, caution is suggested for those with the aforementioned risk factors. PMID- 28992429 TI - Adverse Effects of Nutraceuticals and Dietary Supplements. AB - Over 70% of Americans take some form of dietary supplement every day, and the supplement industry is currently big business, with a gross of over $28 billion. However, unlike either foods or drugs, supplements do not need to be registered or approved by the US Food and Drug Administration (FDA) prior to production or sales. Under the Dietary Supplement Health and Education Act of 1994, the FDA is restricted to adverse report monitoring postmarketing. Despite widespread consumption, there is limited evidence of health benefits related to nutraceutical or supplement use in well-nourished adults. In contrast, a small number of these products have the potential to produce significant toxicity. In addition, patients often do not disclose supplement use to their physicians. Therefore, the risk of adverse drug-supplement interactions is significant. An overview of the major supplement and nutraceutical classes is presented here, together with known toxic effects and the potential for drug interactions. PMID- 28992427 TI - Effects of cannabinoid receptor type 2 in respiratory syncytial virus infection in human subjects and mice. AB - An accumulating body of evidence suggests that the endocannabinoid system plays a significant role in pathophysiological processes and impacts disease severity. Here we investigate the possible role of a cannabinoid receptor type 2 (CB2) functional variant in determining disease severity and the potential pharmacological therapeutic effects of CB2 activation in viral respiratory infection. The common missense variant (CAA/CGG; Q63R) of the gene-encoding CB2 receptor (CNR2) was evaluated in 90 inpatient and 90 outpatient children with acute respiratory tract infection (ARTI). The frequency distribution of respiratory syncytial virus (RSV)-the main cause of severe cases of bronchiolitis and pneumonia in children-was studied in all collected samples. The mechanism through which CB2 affects clinical outcomes in case of RSV infection was studied in Balb/c mice model using AM630 as a CB2 antagonist. The potential therapeutic effect of CB2 activation during RSV infection was studied using a selective agonist, JWH133. The CB2 Q63R variation was associated with increased risk of hospitalization in children with ARTI. Children carrying the QQ genotype were more prone to developing severe ARTI (OR = 3.275, 95% CI: 1.221-8.705; p = 0.019). Of all the children enrolled in the study, 83 patients (46.1%) were found positive for RSV infection. The associated risk of developing severe ARTI following RSV infection increased more than two-fold in children carrying the Q allele (OR = 2.148, 95% CI: 1.092-4.224; p = 0.026). In mice, the blockade of CB2 by AM630 during RSV infection enhanced the influx of BAL cells and production of cytokines/chemokines while exaggerating lung pathology. CB2 activation by JWH133 reduces the influx of BAL cells and production of cytokines/chemokines while alleviating lung pathology. Collectively, CB2 is associated with RSV severity during infancy and may serve as a therapeutic target in RSV infection through the alleviation of virus-associated immunopathology. PMID- 28992430 TI - Human Induced Pluripotent Stem Cell (hiPSC)-Derived Cells to Assess Drug Cardiotoxicity: Opportunities and Problems. AB - Billions of US dollars are invested every year by the pharmaceutical industry in drug development, with the aim of introducing new drugs that are effective and have minimal side effects. Thirty percent of in-pipeline drugs are excluded in an early phase of preclinical and clinical screening owing to cardiovascular safety concerns, and several lead molecules that pass the early safety screening make it to market but are later withdrawn owing to severe cardiac side effects. Although the current drug safety screening methodologies can identify some cardiotoxic drug candidates, they cannot accurately represent the human heart in many aspects, including genomics, transcriptomics, and patient- or population-specific cardiotoxicity. Despite some limitations, human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) are a powerful and evolving technology that has been shown to recapitulate many attributes of human cardiomyocytes and their drug responses. In this review, we discuss the potential impact of the inclusion of the hiPSC-CM platform in premarket candidate drug screening. PMID- 28992428 TI - Inflammatory Mediators in Mood Disorders: Therapeutic Opportunities. AB - Mood disorders such as depression are among the most prevalent psychiatric disorders in the United States, but they are inadequately treated in a substantial proportion of patients. Accordingly, neuropsychiatric research has pivoted from investigation of monoaminergic mechanisms to exploration of novel mediators, including the role of inflammatory processes. Subsets of mood disorder patients exhibit immune-related abnormalities, including elevated levels of proinflammatory cytokines, monocytes, and neutrophils in the peripheral circulation; dysregulation of neuroglia and blood-brain barrier function; and disruption of gut microbiota. The field of psychoneuroimmunology is one of great therapeutic opportunity, yielding experimental therapeutics for mood disorders, such as peripheral cytokine targeting antibodies, microglia and astrocyte targeting therapies, and probiotic treatments for gut dysbiosis, and producing findings that identify therapeutic targets for future development. PMID- 28992431 TI - Model-Informed Drug Development for Malaria Therapeutics. AB - Malaria is a critical public health problem resulting in substantial morbidity and mortality, particularly in developing countries. Owing to the development of resistance toward current therapies, novel approaches to accelerate the development efforts of new malaria therapeutics are urgently needed. There have been significant advancements in the development of in vitro and in vivo experiments that generate data used to inform decisions about the potential merit of new compounds. A comprehensive disease-drug model capable of integrating discrete data from different preclinical and clinical components would be a valuable tool across all stages of drug development. This could have an enormous impact on the otherwise slow and resource-intensive process of traditional clinical drug development. PMID- 28992432 TI - The Mystery of the Interstitial Cells in the Urinary Bladder. AB - Intrinsic mechanisms to restrain smooth muscle excitability are present in the bladder, and premature contractions during filling indicate a pathological phenotype. Some investigators have proposed that c-Kit+ interstitial cells (ICs) are pacemakers and intermediaries in efferent and afferent neural activity, but recent findings suggest these cells have been misidentified and their functions have been misinterpreted. Cells reported to be c-Kit+ cells colabel with vimentin antibodies, but vimentin is not a specific marker for c-Kit+ cells. A recent report shows that c-Kit+ cells in several species coexpress mast cell tryptase, suggesting that they are likely to be mast cells. In fact, most bladder ICs labeled with vimentin antibodies coexpress platelet-derived growth factor receptor alpha (PDGFRalpha). Rather than an excitatory phenotype, PDGFRalpha+ cells convey inhibitory regulation in the detrusor, and inhibitory mechanisms are activated by purines and stretch. PDGFRalpha+ cells restrain premature development of contractions during bladder filling, and overactive behavior develops when the inhibitory pathways in these cells are blocked. PDGFRalpha+ cells are also a prominent cell type in the submucosa and lamina propria, but little is known about their function in these locations. Effective pharmacological manipulation of bladder ICs depends on proper identification and further study of the pathways in these cells that affect bladder functions. PMID- 28992433 TI - KCNQ-Encoded Potassium Channels as Therapeutic Targets. AB - Kv7 channels are voltage-gated potassium channels encoded by KCNQ genes that have a considerable physiological impact in many cell types. This reliance upon Kv7 channels for normal cellular function, as well as the existence of hereditary disorders caused by mutations to KCNQ genes, means that pharmacological targeting of these channels has broad appeal. Consequently, a plethora of chemical entities that modulate Kv7 channel activity have been developed. Moreover, Kv7 channels are influenced by many disparate intracellular mediators and trafficking processes, making upstream targeting an appealing prospect for therapeutic development. This review covers the main characteristics of these multifunctional and versatile channels with the aim of providing insight into the therapeutic value of targeting these channels. PMID- 28992435 TI - Introduction: The Challenge to Science in the Arena of Public Policy. PMID- 28992436 TI - Sex and Gender Differences in the Outcomes of Vaccination over the Life Course. AB - Both sex (i.e., biological differences) and gender (i.e., social or cultural influences) impact vaccine acceptance, responses, and outcomes. Clinical data illustrate that among children, young adults, and aged individuals, males and females differ in vaccine-induced immune responses, adverse events, and protection. Although males are more likely to receive vaccines, following vaccination, females typically develop higher antibody responses and report more adverse effects of vaccination than do males. Human, nonhuman animal, and in vitro studies reveal numerous immunological, genetic, hormonal, and environmental factors that differ between males and females and contribute to sex- and gender specific vaccine responses and outcomes. Herein, we address the impact of sex and gender variables that should be considered in preclinical and clinical studies of vaccines. PMID- 28992434 TI - Targeting Epigenetics in Cancer. AB - Alterations of genes regulating epigenetic processes are frequently found as cancer drivers and may cause widespread alterations of DNA methylation, histone modification patterns, or chromatin structure that disrupt normal patterns of gene expression. Because of the inherent reversibility of epigenetic changes, inhibitors targeting these processes are promising anticancer strategies. Small molecules targeting epigenetic regulators have been developed recently, and clinical trials of these agents are under way for hematologic malignancies and solid tumors. In this review, we describe how the writers, readers, and erasers of epigenetic marks are dysregulated in cancer and summarize the development of therapies targeting these mechanisms. PMID- 28992437 TI - Assessing the Contributions of Motor Enzymes and Microtubule Dynamics to Mitotic Chromosome Motions. AB - During my graduate work with Keith Porter, I became fascinated by the mitotic spindle, an interest that has motivated much of my scientific work ever since. I began spindle studies by using electron microscopes, instruments that have made significant contributions to our understanding of spindle organization. Such instruments have helped to elucidate the distributions of spindle microtubules, the interactions among them, their molecular polarity, and their associations with both kinetochores and spindle poles. Our lab has also investigated some processes of spindle physiology: microtubule dynamics, the actions of microtubule associated proteins (including motor enzymes), the character of forces generated by specific spindle components, and factors that control mitotic progression. Here, I give a personal perspective on some of this intellectual history and on what recent discoveries imply about the mechanisms of chromosome motion. PMID- 28992439 TI - Temporal Patterning in the Drosophila CNS. AB - A small pool of neural progenitors generates the vast diversity of cell types in the CNS. Spatial patterning specifies progenitor identity, followed by temporal patterning within progenitor lineages to expand neural diversity. Recent work has shown that in Drosophila, all neural progenitors (neuroblasts) sequentially express temporal transcription factors (TTFs) that generate molecular and cellular diversity. Embryonic neuroblasts use a lineage-intrinsic cascade of five TTFs that switch nearly every neuroblast cell division; larval optic lobe neuroblasts also use a rapid cascade of five TTFs, but the factors are completely different. In contrast, larval central brain neuroblasts undergo a major molecular transition midway through larval life, and this transition is regulated by a lineage-extrinsic cue (ecdysone hormone signaling). Overall, every neuroblast lineage uses a TTF cascade to generate diversity, illustrating the widespread importance of temporal patterning. PMID- 28992440 TI - Coping with Protein Quality Control Failure. AB - Cells and organisms have evolved numerous mechanisms to cope with and to adapt to unexpected challenges and harsh conditions. Proteins are essential to perform the vast majority of cellular and organismal functions. To maintain a healthy proteome, cells rely on a network of factors and pathways collectively known as protein quality control (PQC) systems, which not only ensure that newly synthesized proteins reach a functional conformation but also are essential for surveillance, prevention, and rescue of protein defects. The main players of PQC systems are chaperones and protein degradation systems: the ubiquitin-proteasome system and autophagy. Here we provide an integrated overview of the diverse PQC systems in eukaryotic cells in health and diseases, with an emphasis on the key regulatory aspects and their cross talks. We also highlight how PQC regulation may be exploited for potential therapeutic benefit. PMID- 28992441 TI - Mechanisms of Tail-Anchored Membrane Protein Targeting and Insertion. AB - Proper localization of membrane proteins is essential for the function of biological membranes and for the establishment of organelle identity within a cell. Molecular machineries that mediate membrane protein biogenesis need to not only achieve a high degree of efficiency and accuracy, but also prevent off pathway aggregation events that can be detrimental to cells. The posttranslational targeting of tail-anchored proteins (TAs) provides tractable model systems to probe these fundamental issues. Recent advances in understanding TA-targeting pathways reveal sophisticated molecular machineries that drive and regulate these processes. These findings also suggest how an interconnected network of targeting factors, cochaperones, and quality control machineries together ensures robust membrane protein biogenesis. PMID- 28992438 TI - Proteostatic Tactics in the Strategy of Sterol Regulation. AB - In eukaryotes, the synthesis and uptake of sterols undergo stringent multivalent regulation. Both individual enzymes and transcriptional networks are controlled to meet changing needs of the many sterol pathway products. Regulation is tailored by evolution to match regulatory constraints, which can be very different in distinct species. Nevertheless, a broadly conserved feature of many aspects of sterol regulation is employment of proteostasis mechanisms to bring about control of individual proteins. Proteostasis is the set of processes that maintain homeostasis of a dynamic proteome. Proteostasis includes protein quality control pathways for the detection, and then the correction or destruction, of the many misfolded proteins that arise as an unavoidable feature of protein-based life. Protein quality control displays not only the remarkable breadth needed to manage the wide variety of client molecules, but also extreme specificity toward the misfolded variants of a given protein. These features are amenable to evolutionary usurpation as a means to regulate proteins, and this approach has been used in sterol regulation. We describe both well-trod and less familiar versions of the interface between proteostasis and sterol regulation and suggest some underlying ideas with broad biological and clinical applicability. PMID- 28992442 TI - Cell Sheet Morphogenesis: Dorsal Closure in Drosophila melanogaster as a Model System. AB - Dorsal closure is a key process during Drosophila morphogenesis that models cell sheet movements in chordates, including neural tube closure, palate formation, and wound healing. Closure occurs midway through embryogenesis and entails circumferential elongation of lateral epidermal cell sheets that close a dorsal hole filled with amnioserosa cells. Signaling pathways regulate the function of cellular structures and processes, including Actomyosin and microtubule cytoskeletons, cell-cell/cell-matrix adhesion complexes, and endocytosis/vesicle trafficking. These orchestrate complex shape changes and movements that entail interactions between five distinct cell types. Genetic and laser perturbation studies establish that closure is robust, resilient, and the consequence of redundancy that contributes to four distinct biophysical processes: contraction of the amnioserosa, contraction of supracellular Actomyosin cables, elongation (stretching?) of the lateral epidermis, and zipping together of two converging cell sheets. What triggers closure and what the emergent properties are that give rise to its extraordinary resilience and fidelity remain key, extant questions. PMID- 28992443 TI - Expressive Writing in Psychological Science. AB - The 1997 Psychological Science paper "Writing About Emotional Experiences as a Therapeutic Process" summarized the results of several expressive writing studies. Since the publication of the first expressive writing study in 1986, a number of discoveries had emerged that had both theoretical and clinical implications. The scientific and personal backstories of the research are discussed. Finally, several possible reasons are advanced to explain why this particular paper has been cited as much as it has. PMID- 28992444 TI - Molecular Cloning, Characterization, and Expression Analysis of Cathepsin A in the Chinese Giant Salamander Andrias davidianus. AB - Cathepsin A (CTSA) is serine carboxypeptidase, an important protease in the lysosome. In this study, the full complementary DNA (cDNA) sequence of CTSA in Chinese giant salamanders Andrias davidianus was cloned, and its sequence features were analyzed. Tissue expression patterns of CTSA in healthy and Aeromonas hydrophila-infected salamanders were also investigated. The full cDNA sequence of salamander CTSA was 1,620 base pairs in length, encoding 472 amino acids. Salamander CTSA shared high sequence identities with other vertebrates' CTSAs, ranging from 62.7% to 68.9%. In healthy salamanders, CTSA was highly expressed in spleen, followed by brain, intestine, and stomach. After A. hydrophila infection, salamander CTSA was significantly upregulated in lung, heart, muscle, and kidney; was downregulated in liver, spleen, and intestine; and exhibited no significant changes in stomach and skin, indicating that salamander CTSA might play defense roles in multiple tissues during bacterial infection. These results provide a solid basis for further study of the immune function of amphibian CTSA. Received September 18, 2016; accepted June 18, 2017. PMID- 28992445 TI - The human auditory brainstem response to running speech reveals a subcortical mechanism for selective attention. AB - Humans excel at selectively listening to a target speaker in background noise such as competing voices. While the encoding of speech in the auditory cortex is modulated by selective attention, it remains debated whether such modulation occurs already in subcortical auditory structures. Investigating the contribution of the human brainstem to attention has, in particular, been hindered by the tiny amplitude of the brainstem response. Its measurement normally requires a large number of repetitions of the same short sound stimuli, which may lead to a loss of attention and to neural adaptation. Here we develop a mathematical method to measure the auditory brainstem response to running speech, an acoustic stimulus that does not repeat and that has a high ecological validity. We employ this method to assess the brainstem's activity when a subject listens to one of two competing speakers, and show that the brainstem response is consistently modulated by attention. PMID- 28992446 TI - Effects of benzophenone-3 on the green alga Chlamydomonas reinhardtii and the cyanobacterium Microcystis aeruginosa. AB - Effects of benzophenone-3 (BP-3) on the green alga, Chlamydomonas reinhardtii, and the cyanobacterium, Microcystis aeruginosa, were investigated. The tested organisms were exposed to environmental levels of BP-3 for 10 days, at nominal concentrations from 0.01 to 5000MUgL-1. Specific growth rate and photosynthetic pigments were employed to evaluate the toxic responses. The two tested algae had distinct toxic responses towards BP-3 stress, with the green alga C. reinhardtii being more sensitive than the cyanobacterium M. aeriginosa, based on EC20 and EC50 values. Uptake of BP-3 from the medium occurred in both species, with M. aeruginosa showing greater overall uptake (27.2-77.4%) compared to C. reinhardtii (1.1-58.4%). The effects of BP-3 on C. reinhardtii were variable at concentrations lower than 100MUgL-1. At higher concentrations, the specific growth rate of C. reinhardtii decreased following a reduction in chlorophyll a (chl-a) content. Further experiments showed that BP-3 regulated the growth of C. reinhardtii by affecting the production of chl-a, chlorophyll b and carotenoids. In M. aeruginosa, specific growth rate was only moderately affected by BP-3. Additionally, the production of chl-a was significantly inhibited over the different exposure concentrations, while the production of carotenoids was stimulated. These results indicate a potential detrimental effect on prokaryotes and eukaryotes and that the mechanism of action varies with species. PMID- 28992447 TI - Magnetic hyperthermia efficiency and MRI contrast sensitivity of colloidal soft/hard ferrite nanoclusters. AB - The use of magnetic nanostructures as theranostic agents is a multiplex task as physiochemical and biochemical properties including excellent magneto-responsive properties, low toxicity, colloidal stability and facile surface engineering capability are all required. Nonetheless, much progress has been made in recent years synthesis of "all-in-one" MNPs remain unambiguously challenging. Towards this direction, in this study is presented a facile incorporation of a soft magnetic phase (MnFe2O4 NPs) with a hard phase (CoFe2O4 NPs) in the presence of the biocompatible polymer sodium dodecyl sulfate (SDS), into spherical and compact bi-magnetic nanoclusters (NCs) with modulated magnetic properties that critically enhance hyperthermic efficiency and MRI contrast effect. Hydrophobic MnFe2O4 and CoFe2O4 NPs coated with oleylamine of the same size (9 nm) were used as primary building units for the formation of the bi-magnetic NCs through a microemulsion approach where a set of experiments were conducted to identify the optimal concentration of SDS (19.5 mM) for the cluster formation. Additionally, homo-magnetic NCs of MnFe2O4 NPs and CoFe2O4 NPs, respectively were synthesized for comparative studies. The presence of distinct magnetic phases within the bi magnetic NCs resulting in synergistic behavior, where the soft phase offers moderate coercivity Hc and the hard one high magnetization Ms. Increased specific loss power (SLP) value was obtained for the bi-magnetic system (525 W/g) when compared with the homo-magnetic NCs (104 W/g for MnNCs and 223 W/g for CoNCs) under field conditions of 25 kA/m and 765 kHz. Relaxivities (r2) of the bi magnetic NCs were also higher (81.8 mM-1 s-1) than those of the homo-magnetic NCs (47.4 mM-1 s-1 for MnNCs and 3.1 mM-1 s-1 for CoNCs), while the high r2/r1 value renders the system suitable for T2-weighted MRI imaging. PMID- 28992448 TI - Plasmon enhanced electrocatalytic oxidation of ethanol and organic contaminants on gold/copper iodide composites under visible light irradiation. AB - In this paper, plasmonic photoelectroncatalyst of gold/copper iodide (Au/CuI) was synthesized and fully characterized. Compared to traditional electrocatalytic procedure under dark condition, the photoelectrocatalytic (PEC) activities of Au/CuI towards ethanol oxidation and organic pollutant degradation were distinctly enhanced under visible light irradiation. The advantages of the PEC process were investigated by photocurrent responses, linear sweep voltammetry, chronoamperometric and chronopotentiometry curves, and electrochemical impedance spectroscopy spectra. Finally, the mechanism of plasmon enhanced PEC performance in ethanol oxidation and organic contaminant degradation under visible light irradiation was proposed. The current studies open a new possibility in the application of ethanol oxidation and organic contaminant degradation by using plasmonic photoelectrocatalysts under visible light irradiation. PMID- 28992449 TI - Advances in the use of biologics and other novel drugs for managing inflammatory bowel disease. AB - For the ultimate aim of preventing intestinal disability in inflammatory bowel disease (IBD), the treatment goal has moved from symptom control towards inflammation control (i.e., 'deep remission'). Furthermore, the concept of 'treat to-target' has been adopted to assist in treatment escalation and better control. Although deep remission is possible with current biologics, there are still unmet needs in IBD management. Biosimilars of several biologics will be an increasingly common option in the near future. In this review, we review the current status of novel drugs for IBD, focusing on recent phase 2 and 3 randomized controlled trials, and address the issues of biosimilars. Recent studies of the 'treat-to target' strategy and therapeutic drug monitoring are summarized. PMID- 28992450 TI - Multilevel analysis of the role of human factors in regional disparities in crash outcomes. AB - A growing body of research has examined the disparities in road traffic safety among population groups and geographic regions. These studies reveal disparities in crash outcomes between people and regions with different socioeconomic characteristics. A critical aspect of the road traffic crash epidemic that has received limited attention is the influence of local characteristics on human elements that increase the risk of getting into a crash. This paper applies multilevel logistic regression modeling techniques to investigate the influence of driver residential factors on driver behaviors in an attempt to explain the area-based differences in the severity of road crashes across the State of Alabama. Specifically, the paper reports the effects of characteristics attributable to drivers and the geographic regions they reside on the likelihood of a crash resulting in serious injuries. Model estimation revealed that driver residence (postal code or region) accounted for about 7.3% of the variability in the probability of a driver getting into a serious injury crash, regardless of driver characteristics. The results also reveal disparities in serious injury crash rate as well as significant proportions of serious injury crashes involving no seatbelt usage, driving under influence (DUI), unemployed drivers, young drivers, distracted driving, and African American drivers among some regions. The average credit scores, average commute times, and populations of driver postal codes are shown to be significant predictors for risk of severe injury crashes. This approach to traffic crash analysis presented can serve as the foundation for evidence-based policies and also guide the implementation of targeted countermeasures. PMID- 28992451 TI - Driver compliance to take-over requests with different auditory outputs in conditional automation. AB - Conditionally automated driving (CAD) systems are expected to improve traffic safety. Whenever the CAD system exceeds its limit of operation, designers of the system need to ensure a safe and timely enough transition from automated to manual mode. An existing visual Human-Machine Interface (HMI) was supplemented by different auditory outputs. The present work compares the effects of different auditory outputs in form of (1) a generic warning tone and (2) additional semantic speech output on driver behavior for the announcement of an upcoming take-over request (TOR). We expect the information carried by means of speech output to lead to faster reactions and better subjective evaluations by the drivers compared to generic auditory output. To test this assumption, N=17 drivers completed two simulator drives, once with a generic warning tone ('Generic') and once with additional speech output ('Speech+generic'), while they were working on a non-driving related task (NDRT; i.e., reading a magazine). Each drive incorporated one transition from automated to manual mode when yellow secondary lanes emerged. Different reaction time measures, relevant for the take over process, were assessed. Furthermore, drivers evaluated the complete HMI regarding usefulness, ease of use and perceived visual workload just after experiencing the take-over. They gave comparative ratings on usability and acceptance at the end of the experiment. Results revealed that reaction times, reflecting information processing time (i.e., hands on the steering wheel, termination of NDRT), were shorter for 'Speech+generic' compared to 'Generic' while reaction time, reflecting allocation of attention (i.e., first glance ahead), did not show this difference. Subjective ratings were in favor of the system with additional speech output. PMID- 28992452 TI - Safety analysis of the new synchronized and milwaukee B interchanges in comparison to existing designs. AB - Interchanges have high crash rates and large impacts on traffic operations. The main objective of this research is to analyze the safety performance of two new interchanges, the synchronized interchange and the Milwaukee B interchange. The primary method of study was microscopic simulation modeling using the Surrogate Safety Assessment Model (SSAM) program to estimate the quantity and type of conflicting interactions in each interchange. A comprehensive series of simulation scenarios were considered to include different conditions of traffic volumes, traffic turning ratios, traffic distribution, and heavy vehicles percentages. Afterward, outcomes were analyzed with two-way Analyses of Variance (ANOVAs) to compare the mean values of conflicts. Based on the results, the diverging diamond interchange (DDI) and Milwaukee B were the safest designs regarding observed conflicting interactions in the simulation models; however, the DDI did not seem as reliable from the viewpoint of wrong way movements. The new synchronized interchange, the parclo B, and the Milwaukee A (an existing interchange in Milwaukee, WI) showed the same rate of conflicts. The synchronized interchange may be advantageous because it was estimated to reduce the severity of crashes due to fewer crossing conflicts, a lower speed of conflicts, and a higher time to collision. The conventional diamond was the most dangerous design based on our measures. The DDI and the synchronized interchange look like plausible substitutes for reconstructing an unsafe diamond interchange due to the similarities in their required space. PMID- 28992453 TI - FIFS: A data mining method for informative marker selection in high dimensional population genomic data. AB - BACKGROUND AND OBJECTIVE: Single Nucleotide Polymorphism (SNPs) are, nowadays, becoming the marker of choice for biological analyses involving a wide range of applications with great medical, biological, economic and environmental interest. Classification tasks i.e. the assignment of individuals to groups of origin based on their (multi-locus) genotypes, are performed in many fields such as forensic investigations, discrimination between wild and/or farmed populations and others. Tauhese tasks, should be performed with a small number of loci, for computational as well as biological reasons. Thus, feature selection should precede classification tasks, especially for Single Nucleotide Polymorphism (SNP) datasets, where the number of features can amount to hundreds of thousands or millions. METHODS: In this paper, we present a novel data mining approach, called FIFS - Frequent Item Feature Selection, based on the use of frequent items for selection of the most informative markers from population genomic data. It is a modular method, consisting of two main components. The first one identifies the most frequent and unique genotypes for each sampled population. The second one selects the most appropriate among them, in order to create the informative SNP subsets to be returned. RESULTS: The proposed method (FIFS) was tested on a real dataset, which comprised of a comprehensive coverage of pig breed types present in Britain. This dataset consisted of 446 individuals divided in 14 sub populations, genotyped at 59,436 SNPs. Our method outperforms the state-of-the art and baseline methods in every case. More specifically, our method surpassed the assignment accuracy threshold of 95% needing only half the number of SNPs selected by other methods (FIFS: 28 SNPs, Delta: 70 SNPs Pairwise FST: 70 SNPs, In: 100 SNPs.) CONCLUSION: Our approach successfully deals with the problem of informative marker selection in high dimensional genomic datasets. It offers better results compared to existing approaches and can aid biologists in selecting the most informative markers with maximum discrimination power for optimization of cost-effective panels with applications related to e.g. species identification, wildlife management, and forensics. PMID- 28992454 TI - Tracking the leaving group in the remote activation of O-2-[(propan-2 yl)sulfinyl]benzyl (OPSB) glycoside. AB - In our recently developed interrupted Pummerer reaction mediated glycosylation with O-2-[(propan-2-yl)sulfinyl]benzyl (OPSB) glycosides as glycosyl donors, the anomeric leaving group was recovered as a benzyl alcohol which didn't affect the glycosylation efficiency. To investigate the mechanism of the occurrence of this alcohol, an 18O isotopic labeling reaction was carried out to track the leaving group. It was found that the benzyl alcohol was generated during the aqueous work up process from an inactive cyclic oxo-sulfonium ion intermediate. It was also proved that H2O prefer to attack the sulfur atom position during the hydrolysis of the intermediate. PMID- 28992455 TI - 1H NMR studies of molecular interaction of D-glucosamine and N-acetyl-D glucosamine with capsaicin in aqueous and non-aqueous media. AB - Complex formation of D-glucosamine (Gl) and N-acetyl-D-glucosamine (AGl) with capsaicin (Cp) were studied by 1H NMR titrations in H2O-d2 and DMSO-d6; capsaicin is the major bioactive component of chili peppers. Every titration curve has been interpreted by formulating a suitable model for the reaction equilibrium, to elucidate intermolecular interactions. In DMSO, glucosamine cations associate with each other to yield linear aggregates, and undergo pseudo-1:1-complexation with capsaicin, the formation constant being ca. 30 M-1. N-Acetylglucosamine, without self-association, forms a 2:1-complex AGl2Cp with the stability of ca. 70 M-2. These complexations are achieved by intermolecular hydrogen bonds. In D2O, glucosamine undergoes reversible protonation equilibrium between Gl0 and GlH+ with the logarithmic protonation constants log KD = 8.63 for alpha-glucosamine and 8.20 for beta-isomer. Both anomeric isomers of deprotonated glucosamine form Gl0Cp-type complexes of capsaicin, in a competitive manner, with a formation constant of 1040 M-1 for the alpha-glucosamine complex and 830 M-1 for the beta complex; the anomeric carbons result in the difference in thermodynamic stability. The reactant molecules are closed up by the solvent-exclusion effect and/or the van der Waals interaction; the resulting pair is stabilized by intermolecular hydrogen bonding within a local water-free space between the component molecules. By contrast, neither protonated glucosamine (GlH+) nor N acetylglucosamine yields a capsaicin complex with the definite stoichiometry. The monosaccharides recognize capsaicin under only a controlled condition; the same phenomena are predicted for biological systems and nanocarriers based on polysaccharides such as chitosan. PMID- 28992456 TI - Prediction of new chromene-based inhibitors of tubulin using structure-based virtual screening and molecular dynamics simulation methods. AB - Multidrug resistance (MDR) is one of the serious problems in cancer research that causes failure in chemotherapy. Chromene-based compounds have been proven to be the novel anti-MDR agents for inhibiting proliferation of tumor cells through tubulin polymerization inhibition of by binding at the colchicine binding site. In this study, we screened a chromene-based database of small molecules using physicochemical, ADMET properties and molecular docking to identify potential hit compounds. In order to validate our hit compounds, molecular dynamics simulations and related analysis were carried out and the results suggest that our hit compounds (PubChem CIDs: 16814409, 17594471, 57367244 and 69899719) can prove to be potential inhibitors of tubulin. The in silico results show that the present hits, like colchicine, effectively suppressed the dynamic instability of microtubules and induced microtubule-depolymerization and cell cycle arrest. PMID- 28992457 TI - A parameter for the assessment of the segmentation of TEM tomography reconstructed volumes based on mutual information. AB - A method is proposed and verified for selecting the optimum segmentation of a TEM reconstruction among the results of several segmentation algorithms. The selection criterion is the accuracy of the segmentation. To do this selection, a parameter for the comparison of the accuracies of the different segmentations has been defined. It consists of the mutual information value between the acquired TEM images of the sample and the Radon projections of the segmented volumes. In this work, it has been proved that this new mutual information parameter and the Jaccard coefficient between the segmented volume and the ideal one are correlated. In addition, the results of the new parameter are compared to the results obtained from another validated method to select the optimum segmentation. PMID- 28992458 TI - Quantitative analysis of actin filament assembly in yeast and plant by live cell fluorescence microscopy. AB - Eukaryotic cells depend on a dynamic actin cytoskeleton to regulate many conserved intracellular events such as endocytosis, morphogenesis, polarized cell growth, and cytokinesis (Engqvist-Goldstein and Drubin, 2003; Salbreux et al., 2012; Pruyne et al., 2004; Pollard, 2010). These activities depend on a precise and well-organized spatiotemporal actin assembly that involves many conserved processes found in eukaryotic cells ranging from a unicellular organism, such as yeast, to multicellular organisms, such as plants and human. In particular, both budding yeast Saccharomyces cerevisiae and plant Arabidopsis thaliana have been proven to be the powerful and great model organisms to study the molecular mechanisms of the polymerization of the actin cytoskeleton and the actin-driven processes in walled-cells. Here we describe the methods in imaging and image processing to analyze dynamic actin filament assembly in budding yeast and Arabidopsis using a wide-field fluorescent microscope. PMID- 28992459 TI - Smart operation of nitritation/denitritation virtually abolishes nitrous oxide emission during treatment of co-digested pig slurry centrate. AB - The implementation of nitritation/denitritation (Nit/DNit) as alternative to nitrification/denitrification (N/DN) is driven by operational cost savings, e.g. 1.0-1.8 EUR/ton slurry treated. However, as for any biological nitrogen removal process, Nit/DNit can emit the potent greenhouse gas nitrous oxide (N2O). Challenges remain in understanding formation mechanisms and in mitigating the emissions, particularly at a low ratio of organic carbon consumption to nitrogen removal (CODrem/Nrem). In this study, the centrate (centrifuge supernatant) from anaerobic co-digestion of pig slurry was treated in a sequencing batch reactor. The process removed approximately 100% of ammonium a satisfactory nitrogen loading rate (0.4 g N/L/d), with minimum nitrite and nitrate in the effluent. Substantial N2O emission (around 17% of the ammonium nitrogen loading) was observed at the baseline operational condition (dissolved oxygen, DO, levels averaged at 0.85 mg O2/L; CODrem/Nrem of 2.8) with ~68% of the total emission contributed by nitritation. Emissions increased with higher nitrite accumulation and lower organic carbon to nitrogen ratio. Yet, higher DO levels (~2.2 mg O2/L) lowered the aerobic N2O emission and weakened the dependency on nitrite concentration, suggesting a shift in N2O production pathway. The most effective N2O mitigation strategy combined intermittent patterns of aeration, anoxic feeding and anoxic carbon dosage, decreasing emission by over 99% (down to ~0.12% of the ammonium nitrogen loading). Without anaerobic digestion, mitigated Nit/DNit decreases the operational carbon footprint with about 80% compared to N/DN. With anaerobic digestion included, about 4 times more carbon is sequestered. In conclusion, the low CODrem/Nrem feature of Nit/DNit no longer offsets its environmental sustainability provided the process is smartly operated. PMID- 28992460 TI - Lipid chain saturation and the cholesterol in the phospholipid membrane affect the spectroscopic properties of lipophilic dye nile red. AB - We have studied the effect of composition and the phase state of phospholipid membranes on the emission spectrum, anisotropy and lifetime of a lipophilic fluorescence probe nile red. Fluorescence spectrum of nile red in membranes containing cholesterol has also been investigated in order to get insights into the influence of cholesterol on the phospholipid membranes. Maximum emission wavelength (lambdaem) of nile red in the fluid phase of saturated and unsaturated phospholipids was found to differ by ~10nm. The lambdaem was also found to be independent of chain length and charge of the membrane. However, the lambdaem is strongly dependent on the temperature in the gel phase. The lambdaem and rotational diffusion rate decrease, whereas the anisotropy and lifetime increase markedly with increasing cholesterol concentration for saturated phosoholipids, such as, dimyristoyl phosphatidylcholine (DMPC) in the liquid ordered phase. However, these spectroscopic properties do not alter significantly in case of unsaturated phospholipids, such as, dioleoyl phosphatidylcholine (DOPC) in liquid disordered phase. Interestingly, red edge excitation shift (REES) in the presence of lipid-cholesterol membranes is the direct consequences of change in rotational diffusion due to motional restriction of lipids in the presence of cholesterol. This study provides correlations between the membrane compositions and fluorescence spectral features which can be utilized in a wide range of biophysical fields as well the cell biology. PMID- 28992461 TI - Highly sensitive "turn-on" fluorescent chemical sensor for trace analysis of Cr3+ using electro-synthesized poly(N-(9-fluorenylmethoxycarbonyl)-l-histidine). AB - Trivalent chromium (Cr3+) can cause severely environment pollution, declining quality of edible agro-products in plants and animals, and human diseases. Poly(N (9-fluorenylmethoxycarbonyl)-l-histidine) (PFLH) synthesized by the direct electro-polymerization of its corresponding commercially available monomer in both boron trifluoride diethyl etherate and dichloromethane mixed system. The "turn-on" type fluorescent sensor based on PFLH displayed high sensitivity and selectivity for Cr3+ detecting. The structure of PFLH was rationally proved by 1H NMR spectra, FT-IR spectra, quantum chemical calculations, and its optical properties were characterized. The electro-synthesized PFLH exhibited a "turn-on" fluorescent response towards Cr3+, which was employed as a sensing platform for the "turn-on" fluorescent analysis of Cr3+ in a wide linear range from 5.1nM to 25MUM with a low limit of detection as low as 1.7nM. The possible mechanism of fluorescent "turn-on" sensor based on PFLH for Cr3+ was proposed. The sensor displayed high sensitivity, good selectivity, satisfactory practicability, suggesting that PFLH has potential fluorescent application for "turn-on" sensing Cr3+ in agricultural environments and edible agro-products of plants and animals. PMID- 28992462 TI - A non-destructive spectroscopic study of the decoration of archaeological pottery: from matt-painted bichrome ceramic sherds (southern Italy, VIII-VII B.C.) to an intact Etruscan cinerary urn. AB - A study is presented based on the use of entirely non-destructive spectroscopic techniques to analyze the chemical composition of the painted surface layer of archaeological pottery. This study aims to define both the raw materials and the working technology of ancient potters. Energy-dispersive X-ray analysis, micro Raman spectroscopy, visible and near infrared (NIR) diffuse reflection spectroscopy and external reflection Fourier-transform infrared (FTIR) spectroscopy were applied to matt-painted bichrome pottery sherds (VIII-VII century B.C.) from the site of Incoronata near Metaponto in southern Italy. Two different raw materials, ochre and iron-rich clay, were recognized for the red decoration, while the dark areas resulted to have been obtained by the so-called manganese black technique. In any case, it was demonstrated that the decoration was applied before firing, in spite of its sometimes grainy aspect that could suggest a post-firing application. For the samples with a more sophisticated decorative pattern a red/black/white polychromy was recognized, as the lighter areas correspond to an "intentional white" obtained by the firing of a calcium rich clay. Reflection spectroscopy in the visible-NIR and mid-IR as well as micro Raman spectroscopy were then employed to characterize the decoration of an intact ceramic urn from the Etruscan town of Chiusi, evidencing a post-firing painting based on the use of red ochre, carbon black and lime, possibly imitating the "fresco" technique used in wall paintings. PMID- 28992463 TI - Use of zero order diffraction of a grating monochromator towards convenient and sensitive detection of fluorescent analytes in multi fluorophoric systems. AB - White light excitation fluorescence (WLEF) is known to possess analytical advantage in terms of enhanced sensitivity and facile capture of the entire fluorescence spectral signature of multi component fluorescence systems. Using the zero order diffraction of the grating monochromator on the excitation side of a commercial spectrofluorimeter, it has been shown that WLEF spectral measurements can be conveniently carried out. Taking analyte multi-fluorophoric systems like (i) drugs and vitamins spiked in urine sample, (ii) adulteration of extra virgin olive oil with olive pomace oil and (iii) mixture of fabric dyes, it was observed that there is a significant enhancement of measurement sensitivity. The total fluorescence spectral response could be conveniently analysed using PLS2 regression. This work brings out the ease of the use of a conventional fluorimeter for WLEF measurements. PMID- 28992465 TI - A novel frameshift mutation in the fibrinogen gammaC terminal region, FGG c.1169_1170 del AT, leading to hypofibrinogenemia. PMID- 28992464 TI - Pathogenesis of infections in HIV-infected individuals: insights from primary immunodeficiencies. AB - Following infection with almost any given microorganism other than an emerging pathogen, only a minority of individuals develop life-threatening clinical disease, implying that these individuals have some form of immunodeficiency. A growing number of inherited and acquired immunodeficiencies have been deciphered over the last 50 years. HIV infection is probably the best-known acquired immunodeficiency. It emerged about 40 years ago and precipitates various severe infections, the occurrence of which is associated with a fall in circulating CD4+ T cells. However, despite the strength of this correlation, infection rates differ between patients with similar levels and durations of CD4+ T lymphopenia in the presence or absence of antiretroviral treatment. Moreover, a few infections seem to be less dependent on total CD4+ T-cell levels. The fine detail of the mechanisms underlying these infections is unknown. We discuss here how studies of the human genetics and immunology of some of these infections in patients with primary immunodeficiencies (PIDs) have provided unique insights into their molecular and cellular basis. Defects of specific CD4+ Th-cell subsets account for some of these infections, as best exemplified by Th1* for mycobacteriosis and Th17 for candidiasis. PIDs are individually rare, but collectively much more common than initially thought, with new disorders being discovered at an ever-increasing pace and a global prevalence worldwide approaching that of HIV infection. Studies of known and new PIDs should make it possible to dissect the pathogenesis of most human infections at an unprecedented level of molecular and cellular precision. The predictive, preventive, and therapeutic implications of studies of immunity to infection in PIDs may extend to HIV-infected patients and patients with infectious diseases in other settings. PMID- 28992466 TI - Increased risk of heart failure and atrial fibrillation in heterozygous familial hypercholesterolemia. AB - BACKGROUND AND AIMS: Heart failure (HF) and atrial fibrillation/flutter (AF) are important causes of morbidity and mortality. Subjects with familial hypercholesterolemia (FH) carry a high risk of coronary artery disease (CAD) but it is not known if the risk of HF and AF is increased in FH. The present study investigated the incidence of hospitalization for HF and AF in a genetically verified FH cohort, age 25 years and older, compared to the general population. METHODS: Incidence rates of hospitalization for HF and AF were estimated from national registry data. Standardized incidence ratios (SIRs) were calculated. RESULTS: 4273 genotyped FH patients (51.7% women) with a total observation period of 18,300 patient years were studied. Overall, the expected number of FH patients with HF was 27.7 and the observed number of cases was 54 (SIR (95% CI) 2.0 (1.5 2.6)). The highest excess risk was observed in the age group 25-49 years, where SIRs were 3.8 (1.2-11.8) and 4.2 (2.0-8.8) in women and men, respectively. The total expected number of FH patients with AF was 39.4 while the observed number of cases was 77 (SIR 2.0 (1.6-2.4)). Among FH patients with an incident event of HF, nearly 90% had a previous diagnosis of CAD, and nearly 40% had suffered from a myocardial infarction. CONCLUSIONS: We demonstrate a doubling of the risk of hospitalization for HF or AF in patients with FH. This is could have an important prognostic impact for patients and economic impact for the society. PMID- 28992468 TI - Dronedarone exerts anticoagulant and antiplatelet effects independently of its antiarrhythmic actions. AB - BACKGROUND AND AIMS: Dronedarone reduced the rate of stroke and transient ischemic attack in patients with paroxysmal atrial fibrillation (AF) in the ATHENA trial. This cannot be explained by its antiarrhythmic effect alone and may involve alternative mechanisms. This study aimed to investigate any direct effect of dronedarone on blood thrombogenicity, independent of its antiarrhythmic effects. METHODS: Blood samples from patients with cardiovascular disease (n = 30) taking no anticoagulant or antiplatelet medication except aspirin were incubated with dronedarone's active metabolite (SR35021A) at 66 ng/ml (am-L) and 119 ng/ml (am-H), i.e., minimum and maximum mean Cmax reported after repeated 400 mg BID dosing. A third aliquot of blood was incubated with vehicle (Control). Antithrombotic effects of dronedarone were assessed using Coagulation Time (CT), Clot Formation Rate (CFR) and Maximum Clot Firmness (MCF) in ThromboElastoMetry and whole blood platelet aggregation in response to ADP, collagen and TRAP. RESULTS: Compared to Control, mean CT was prolonged by am-L and am-H (164 +/- 25 s vs. 180 +/- 22 and 182 +/- 32 s, respectively, p<0.01 for both). Small but statistically significant reductions were observed in CFR (am-L and am-H) and MCF (am-H). Platelet aggregation induced by ADP and TRAP was also reduced (p<0.05 for both) by am-H. CONCLUSIONS: Dronedarone exerts direct anticoagulant and antiplatelet effects on human blood in vitro that are independent of its antiarrhythmic actions. This suggests the reductions in ischemic events reported with dronedarone may not be due to amelioration of AF itself. Additional clinical studies are required to further improve understanding of the mechanisms involved. PMID- 28992467 TI - Effect of statin on arginine metabolites in treated HIV-infection. AB - BACKGROUND AND AIMS: Asymmetric dimethylarginine (ADMA) is an inhibitor of nitric oxide and an independent risk factor for cardiovascular disease. We examined the effect of statin on ADMA in HIV + patients on stable ART, and whether such an effect contributes to the favorable changes on carotid intima media thickness. METHODS: This is a secondary analysis of SATURN-HIV, in which HIV + adults on stable ART with HIV-1 RNA< 1000 copies/mL and LDL-cholesterol <130 mg/dL were randomized to 10 mg daily rosuvastatin or placebo. Arginine metabolites, ADMA, and markers of inflammation were assessed at baseline and 48 weeks. Carotid intima media thickness (c-IMT) was measured at baseline, 48 and 96 weeks. Spearman correlations, and linear mixed-effect models were used to study relationships among variables. RESULTS: Overall, 79% were male, 68% African Americans, with a median age of 46 years. In the statin arm, no change in ADMA levels was observed at 48 weeks (0.70%), whereas a trend towards an increase in ADMA levels (23.78%) was observed in the placebo group (p = 0.06). Elevated baseline ADMA (highest tertile) was associated with a 0.04 mm increase in c-IMT (p = 0.03) after adjusting for statin and study duration. No interaction was seen between baseline ADMA and statin randomization on change in c-IMT (p = 0.21). CONCLUSIONS: In HIV + subjects on ART, rosuvastatin suppressed the increase over time in ADMA levels. Elevated baseline levels of ADMA were associated with increases in c-IMT, regardless of statin assignment. The favorable effect of rosuvastatin on c-IMT appears to be independent of the arginine pathway. PMID- 28992469 TI - Consumption of fish and vascular risk factors: A systematic review and meta analysis of intervention studies. AB - BACKGROUND AND AIMS: Epidemiological evidence of the beneficial health effects of fish consumption is strong, but the evidence from intervention trials is less documented. Our aim was to evaluate the state of the evidence on the potential effects of fish consumption on vascular risk factors arising from intervention trials. METHODS: A systematic literature search was undertaken in OVID MEDLINE, Scopus, and EMBASE, which were searched from inception to June 2017. A meta analysis of intervention trials was performed to estimate the effect of fish consumption on vascular risk factors in adults (age >18 years). Primary outcomes included lipid biomarkers such as triglycerides, total cholesterol, HDL cholesterol and LDL cholesterol, and also novel biomarkers of vascular risk. Secondary outcomes were related to feasibility and acceptability aspects of these interventions. Random-effects models were used to determine the pooled effect sizes. RESULTS: 14 trials, including a total of 1378 individuals, fulfilled the inclusion criteria for this study. Consuming oily fish was associated with significant reductions in plasma triglycerides (-0.11 mmol/L; 95% CI -0.18 to 0.04; p = 0.002). While a significant increase in HDL-cholesterol was observed (0.06 mmol/L, 95% CI 0.02 to -0.11; p = 0.008). No significant effect could be observed on other vascular risk factors. CONCLUSIONS: This study showed that there is evidence indicating that consuming oily fish led to significant improvements in two important biomarkers of cardiovascular risk, such as triglycerides and HDL levels. These results strongly support the important role for oily fish as part of a healthy diet. PMID- 28992470 TI - The potential effects of efavirenz on Oreochromis mossambicus after acute exposure. AB - Antiretroviral drugs (ARVs) are hazardous therapeutic pharmaceuticals present in South African surface water. Efavirenz is an ARV commonly used in human immunodeficiency virus (HIV) treatment in South Africa. Although little is known about the toxic effects of efavirenz on fish health, threats of toxicity to the aquatic environment have been reported. Oreochromis mossambicus were exposed under controlled conditions to environmentally-relevant efavirenz concentrations (10.3ng/l) as measured in rivers that flow into the Nandoni Dam in the Vhembe District, South Africa. Acute (96h) exposures were conducted using efavirenz concentrations of 10.3ng/l and 20.6ng/l. The overall health of exposed fish was determined using a histology-based fish health assessment index. Necropsies and haematology were conducted and somatic indices calculated after which the liver, kidney, heart, gills and gonads were microscopically quantitatively assessed. Results indicated that fish exposed to 20.6ng/l efavirenz had significantly (p<0.02) higher liver indices than the control fish, indicating increased liver damage including steatosis and frank necrosis. Fish exposed to 20.6ng/l efavirenz presented with significantly (p<0.02) higher total fish indices, representative of declined overall health compared to control fish. It was concluded that the exposure of O. mossambicus to efavirenz resulted in liver damage and overall decline in fish health. These novel findings may indicate a health risk for O. mossambicus and other biota exposed to efavirenz in aquatic ecosystems. Thus, ARV's in water sources of South Africa pose a definite threat to wildlife and ultimately human health. PMID- 28992471 TI - Parkia speciosa empty pod prevents hypertension and cardiac damage in rats given N(G)-nitro-l-arginine methyl ester. AB - Parkia speciosa Hassk is a plant found abundantly in Southeast Asia region. Its seeds with or without pods and roots have been used in traditional medicine in this region to treat hypertension. Therefore, we aimed to investigate the potential effect of the plant empty pod extract on hypertension development and changes in heart induced by N(G)-nitro-l-arginine methyl ester (l-NAME) administration in rats. Twenty-four male Sprague Dawley rats were divided into four groups. Groups 1 to 3 were given l-NAME (25mg/kg, intraperitoneally) for 8 weeks. Groups 2 and 3 were also given Parkia speciosa empty pods methanolic extract (800mg/kg, orally) and nicardipine (3mg/kg, orally), concurrently with l NAME. The last group served as the control. l-NAME reduced plasma nitric oxide level and therefore, increased systolic blood pressure, angiotensin-converting enzyme and NADPH oxidase activities as well as lipid peroxidation in the heart. Parkia speciosa extract and nicardipine treatments had significantly prevented the elevations of blood pressure, angiotensin-converting enzyme, NADPH oxidase activities and lipid peroxidation in the heart induced by the l-NAME. Parkia speciosa extract but not nicardipine prevented the reduction in plasma nitric oxide level caused by l-NAME. In conclusion, Parkia speciosa empty pods methanolic extract has a potential to prevent the development of hypertension possibly by preventing the loss of plasma nitric oxide, as well as has cardioprotective effects by reducing angiotensin-converting enzyme activity and oxidative stress in the heart in rats administered l-NAME. PMID- 28992472 TI - LncRNA ZEB2-AS1 promotes bladder cancer cell proliferation and inhibits apoptosis by regulating miR-27b. AB - BACKGROUND: The aim of this study was to explore the role of lncRNA zinc finger E box binding homeobox 2 antisense RNA 1 (ZEB2-AS1), as a new tumor-associated lncRNA, in bladder cancer (BC) pathogenesis. METHODS: BC tissues and tumor adjacent normal bladder tissues were collected for detection of the expression profile of ZEB2-AS1 and miR-27b in BC. The endogenous expression of ZEB2-AS1 and miR-27b was modulated by the recombinant expression vector in vitro. The interaction between ZEB2-AS1 and miR-27b was identified by luciferase report gene assays and RNA immunoprecipitation (RIP) assays. The proliferation and apoptosis of BC cells was determined using CCK-8 assays and flow cytometric analysis. RESULTS: The expression of ZEB2-AS1 was significantly increased in both BC tissues and BC cells (J82, 5637, T24); while miR-27b was down-regulated in BC tissues. More importantly, ZEB2-AS1 was significantly negative correlated with miR-27b expression in BC tissues (R2=0.1688, P<0.05). ZEB2-AS1 silencing inhibited BC cell proliferation and promoted apoptosis. Further studies confirmed that miR-27b was negatively regulated by ZEB2-AS1 in BC cells 5637 and T24, and the effects of ZEB2-AS1 on BC cells was mediated by miR-27b. CONCLUSION: Our data provided strong evidence that ZEB2-AS1 promoted tumorigenesis and development of BC through down-regulating tumor-suppressive miR-27b. PMID- 28992473 TI - Chronic toxicity in Ceriodaphnia dubia induced by graphene oxide. AB - The unique physico-chemical properties of nanomaterials have allowed their application in different areas including electronics, energy storage, nanomedicine, environmental remediation and biotechnology. Graphene and its derivatives, in particular, have been commercially available, with prediction for increasing their production in the next years, in a way that their release into aquatic environments is very likely to occur, and the impacts of such situation on organisms are still not completely understood. In this context, we evaluated graphene oxide (GO) effects on the freshwater cladoceran Ceriodaphnia dubia through acute and chronic toxicity, feeding rates, and reactive oxygen species (ROS) generation. The mean effective concentration (EC50) estimated during acute exposure was 1.25 mg L-1 of GO. The chronic exposure resulted in significant decrease in the number of neonates. The feeding rates were also decreased by GO exposure. Sub-lethal concentrations of GO caused an increase in ROS generation in the organisms. Our results indicated that GO cause acute and chronic effects to C. dubia. In the presence of GO there was a shift in the available energy for self-maintenance rather than feeding or reproduction activities. This study provides useful information on GO concentrations that might impair the aquatic biota, and supports regulatory efforts concerning the environmental safety of this product. PMID- 28992474 TI - UV-driven hydroxyl radical oxidation of tris(2-chloroethyl) phosphate: Intermediate products and residual toxicity. AB - Organophosphorus esters (OPEs) are emerging contaminants widely applied as annexing agents in a variety of industrial products, and they are robust against conventional wastewater treatments. Ultraviolet-driven (UV) radical-based advanced oxidation processes have a potential to become cost-effective treatment technologies for the removal of OPEs in water matrix, but residual and newly generated toxicities of degradation products are a concern. This study is a comprehensive attempt to evaluate UV/H2O2 for the degradation of a water dissolved OPE, tris(2-chloroethyl) phosphate (TCEP). In ultrapure water, a pseudo first order reaction was observed, and the degradation rate constant reached 0.155 min-1 for 3.5 MUM TCEP using 7.0 mW cm-2 UV irradiation with 44.0 MUM H2O2. Hydroxyl radicals were involved in the oxidative degradation of TCEP, as demonstrated by the quenching of the degradation reaction in the presences of tertiary butanol or ethanol. High resolution mass spectroscopy data showed a partial transformation of TCEP to a series of hydroxylated and dechlorinated products e.g., C4H9Cl2O4P, C6H13Cl2O5P and C2H6ClO4P. Based on proteomics data at molecular and metabolic network levels, the toxicity of TCEP products was reduced obviously as the reaction proceeded, which was confirmed by the up-regulated tricarboxylic acid cycle, fatty acid metabolism and amino acid metabolism in Escherichia coli cells exposed to degradation products mixture. In conclusion, incomplete hydroxylation and dechlorination of TCEP likewise are effective for its detoxification, indicating that UV/H2O2 can be a promising treatment method for OPEs removal. PMID- 28992475 TI - Nickel phytoextraction through bacterial inoculation in Raphanus sativus. AB - A pot experiment was conducted to evaluate the potential of two plant growth promoting rhizobacteria (PGPR) viz. Bacillus sp. CIK-516 and Stenotrophomonas sp. CIK-517Y for improving the growth and Ni uptake of radish (Raphanus sativus) in the presence of four different levels of Ni contamination (0, 50, 100, 150 mg Ni kg-1 soil). Plant growth, dry biomass, chlorophyll and nitrogen contents were significantly reduced by the exogenous application of Ni, however, bacterial inoculation diluted the negative impacts of Ni stress on radish by improving these parameters. PGPR strain CIK-516 increased root length (9-27%), shoot length (8-27%), root dry biomass (2-32%), shoot dry biomass (9-51%), root girth (6-48%), total chlorophyll (4-38%) and shoot nitrogen contents (11-15%) in Ni contaminated and non-contaminated soils. Positive regulation of chlorophyll and nitrogen contents by the inoculated plants shows plant tolerance mechanism of Ni stress. Bacterial strain (CIK-516) exhibited indole acetic acid and 1-amino-cyclopropane 1-carboxylate deaminase potentials which would have helped radish plant to stabilize in Ni contaminated soil and thereby increased Ni uptake (24-257 in shoot and 58-609 in root mg kg-1 dry biomass) and facilitated accumulation in radish (bioaccumulation factor = 0.6-1.7) depending upon soil Ni contamination. Based on the findings of this study, it might be suggested that inoculation with bacterial strain CIK-516 could be an efficient tool for enhanced Ni phytoextraction in radish. PMID- 28992476 TI - Pharmacokinetics and effects of tetrabromobisphenol a (TBBPA) to early life stages of zebrafish (Danio rerio). AB - In silico and in vivo approaches were combined in an aggregate exposure pathway (AEP) to assess accumulation and effects of waterborne exposures of early life stages of zebrafish (Danio rerio) to tetrabromobisphenol A (TBBPA). Three metabolites, two of which were isomers, were detected in fish. Two additional metabolites were detected in the exposure solution. Based on kinetics modeling, proportions of TBBPA that were bioaccumulated and metabolized were 19.33% and 8.88%, respectively. Effects of TBBPA and its metabolites were predicted by use of in silico, surflex-Dock simulations that they were capable of interacting with ThRalpha and activating associated signaling pathways. TBBPA had a greater toxic contribution than its metabolites did when we evaluated the toxicity of these substances based on the toxicity unit method. The half of the internal lethal dose (ILD50) was 18.33 MUg TBBPA/g at 74 hpf. This finding was further confirmed by changes in expressions of ThRalpha and other NRs as well as associated genes in their signal pathways. Specifically, exposure to 1.6 * 102, 3.3 * 102 or 6.5 * 102 MUg TBBPA/L significantly down-regulated expression of ThRalpha and associated genes, ncor, c1d, ncoa2, ncoa3, and ncoa4, in the AR pathway and of er2a and er2b genes in the ER pathway. PMID- 28992477 TI - Cell cycle regulation and apoptosis mediated by p53 in response to hypoxia in hepatopancreas of the white shrimp Litopenaeus vannamei. AB - Although hypoxic aquatic environments cause negative effects on shrimp, these animals can withstand somewhat hypoxia, but the cellular mechanisms underlying this capacity are still poorly understood. In humans, mild hypoxia causes the induction of many proteins to allow cell survival. In contrast, apoptosis is induced during severe hypoxia leading to cell death. p53 is a key transcription factor that determines cells fate towards cell cycle arrest or induction of apoptosis in humans. The aim of this work was to study the role of p53 in cell cycle regulation and apoptosis in response to hypoxia in hepatopancreas of the white shrimp Litopenaeus vannamei. p53 was silenced by RNAi and afterwards the shrimp were exposed to hypoxia. Cdk-2 was used as indicator of cell cycle progression while caspase-3 expression and caspase activity were analyzed as indicators of apoptosis. p53 levels in hepatopancreas were significantly higher at 48 h after hypoxic treatment. Increased expression levels of Cdk-2 were found in p53-silenced shrimp after 24 and 48 h in the normoxic treatments as well as 48 h after hypoxia, indicating a possible role of p53 in cell cycle regulation. In response to hypoxia, unsilenced shrimp showed an increase in caspase-3 expression levels, however an increase was also observed in caspase activity at 24 h of normoxic conditions in p53-silenced shrimps. Taken together these results indicate the involvement of p53 in regulation of cell cycle and apoptosis in the white shrimp in response to hypoxia. PMID- 28992478 TI - Mechanisms of biochar assisted immobilization of Pb2+ by bioapatite in aqueous solution. AB - Bioapatite (BAp) is regarded as an effective material to immobilize lead (Pb2+) via the formation of stable pyromorphite. However, when applied in contaminated soil, due to its low surface area and low adsorption capacity, BAp might not sufficiently contact and react with Pb2+. Biochar, a carbon storage material, typically has high surface area and high adsorption capacity. This study investigated the feasibility of using biochar as a reaction platform to enhance BAp immobilization of Pb2+. An alkaline biochar produced from wheat straw pellets (WSP) and a slightly acidic biochar produced from hardwood (SB) were selected. The results of aqueous adsorption showed the combination of biochar (WSP or SB) and BAp effectively removed Pb2+ from the aqueous solution containing 1000 ppm Pb2+. XRD, ATR-IR, and SEM/EDX results revealed the formation of hydroxypyromorphite on both biochars' surfaces. This study demonstrates that biochars could act as an efficient reaction platform for BAp and Pb2+ in aqueous solution due to their high surface area, porous structure, and high adsorption capacity. Therefore, it is mechanistically feasible to apply biochar to enhance BAp immobilization of Pb2+ in contaminated soil. PMID- 28992479 TI - Bioaccumulation of UV filters in Mytilus galloprovincialis mussel. AB - In this study the bioaccumulation kinetics of organic UV filters, such as 4-MBC, BP-3, BP-4, OC and OD-PABA in wild Mytilus galloprovincialis mussels was investigated. The uptake and accumulation of waterborne 4-MBC, BP-4 and OC was very rapid, and after only 24 h of exposure to 1 MUg L-1, the tissular concentrations were 418, 263 and 327 MUg kg-1d.w., respectively. The kinetics of bioaccumulation of BP-4 and OC significantly fitted to an asymptotic model with BCF values of 905 L kg-1 and 2210 L kg-1, respectively. Measured bioaccumulation of the hydrophilic chemical BP-4 was much higher than predicted by Kow-based bioconcentration models, which would lead to a marked underestimation of actual risk. On the other hand, the patterns of uptake found for BP-3 and OD-PABA suggest biotransformation ability of mussels for these two chemicals. PMID- 28992480 TI - Zearalenone (ZEA)-induced intestinal inflammation is mediated by the NLRP3 inflammasome. AB - To ascertain whether zearalenone (ZEA) could induce intestinal inflammation and investigate its possible mechanism, we investigated inflammatory cytokine release and the activation of the NLRP3 inflammasome after ZEA treatment both in vitro or in vivo. First, intestinal porcine enterocyte cell line (IPEC-J2) cells and mouse peritoneal macrophages were treated with ZEA to detect NLRP3 inflammasome activation, and the role of reactive oxygen species (ROS) in ZEA-induced inflammation was investigated. Then, Balb/c mice were fed a gavage of ZEA, and the disease activity indices (DAIs) and histological analysis were used to assess intestinal inflammation. Our study showed that the mRNA expression of NLRP3 inflammasome, pro-interleukin-1beta (pro-IL-1beta), and pro-interleukin-18 (pro IL-18) was up-regulated 0.5- to 1-fold and that the release of IL-1beta and IL-18 increased from 48 pg mL-1 to 55 pg mL-1 and 110 pg mL-1 to 145 pg mL-1, respectively. However, ROS inhibitor N-acetyl-l-cysteine (NAC) reduced IL-1beta and IL-18 release to 45 pg mL-1 and 108 pg mL-1. Moreover, the same phenomenon was observed in intestinal tissues of ZEA-treated mice. In addition, clinical parameters of treated mice showed stools became loose and contained mucous. In addition, the presence of gross blood stool was found in the last 2 d. Histological analysis showed obvious inflammatory cell infiltration and tissue damage in the colon. These findings uncovered a possible mechanism of intestinal mucosal innate immunity in response to mycotoxin ZEA that ZEA could activate the ROS-mediated NLRP3 inflammasome and, in turn, contribute to the caspase-1 dependent activation of the inflammatory cytokines IL-1beta and IL-18. PMID- 28992481 TI - Evaluation of the sorption mechanism of ionic liquids onto multi-walled carbon nanotubes. AB - The knowledge of the sorption mechanism of different chemicals onto third generation carbon sorbents such as carbon nanotubes (CNTs) is needed in order to project systems for the effective removal of pollutants from the environment. This paper reports evaluation of the sorption mechanism of selected ionic liquids (ILs), being considered as potential pollutant in environment, onto various CNTs. CNTs characterized by the smallest diameter and the biggest surface area showed the highest sorption capacity to isolate ILs from an aqueous solution. CNTs with a bigger diameter, a functionalized surface and particularly a helical shape showed a lower sorption capacity. The sorption mechanism has been defined as complex, including van der Waals, pi-pi and electrostatic interactions with dominating pi-pi interactions. Due to the relatively high sorption coefficient (355.98 +/- 20.69-6397.10 +/- 355.42 L kg-1 depending on the IL) the study showed that multi-walled carbon nanotubes can potentially be used to effectively isolate ILs from an aqueous solution. Moreover, proved in this study, the fast sorption kinetic, and uncomplicated regeneration process, leading to an even higher sorption capacity, means that CNTs are promising material which could find potential applications in the treatment of water contaminated by ILs. PMID- 28992482 TI - Bisphenol A in artificial soil: Effects on growth, reproduction and immunity in earthworms. AB - The application of biosolids in agricultural fields is increasing annually. They contain not only nutrients but also xenobiotics, such as Bisphenol A (BPA). These compounds are not regulated in the use of biosolids in agriculture, which highlights the need to assess their effects on soil life, of which earthworms are most abundant of the animal representatives. In this study the effect of BPA on life-history parameters, such as mortality, growth and reproduction, and on immunity, is evaluated for Dendrobaena veneta and Eisenia fetida. Sublethal concentrations were evaluated by a modified OECD artificial soil test. Decline in growth with increasing concentration of BPA was detected during the first two weeks and the opposite effect for the next two, although these differences were only significant at the highest concentration. Reproduction traits were only significantly different for E. fetida, for which the number of juveniles decreased at higher concentrations, thus showing different sensitivity in both species. By using a contact test, the potentially harmful effect of direct contact with BPA was shown to be much higher than in soil (resembling natural) conditions. Finally, results indicate that BPA may not affect the immune system of these animals, at least in terms of coelomocyte viability. PMID- 28992483 TI - Impacts of inorganic anions and natural organic matter on thermally activated persulfate oxidation of BTEX in water. AB - The present study investigated the impacts of water matrix constituents (CO32-, HCO3-, Cl-, Br-, PO43-, HPO42-, H2PO4-, NO3-, SO42- and natural organic matters (NOM) on the oxidation of a mixture of benzene, toluene, ethylbenzene, and xylenes (BTEX) by thermally activated persulfate (PS). In the absence of matrix constituents, the BTEX oxidation rates decreased in the following order: xylenes > toluene ~ ethylbenzene > benzene. HCO3-/CO32- and NOM inhibited the BTEX oxidation and the inhibiting effects became more pronounced as the HCO3-/CO32 /NOM concentration increased. SO42-, NO3-, PO43- and H2PO4- did not affect the BTEX oxidation while HPO42- slightly inhibited the reaction. The impacts of Cl- and Br- were complex. Cl- inhibited the benzene oxidation while 100 mM and 500 mM of Cl- promoted the oxidation of m-xylene and p-xylene. Br- completely suppressed the benzene oxidation while 500 mM of Br- strongly promoted the oxidation of xylenes. Detailed explanations on the influence of each matrix constituent were discussed. In addition, various halogenated degradation byproducts were detected in the treatments containing Cl- and Br-. Overall, this study indicates that some matrix constituents such as NOM, HCO3-, CO32-, H2PO4-, Cl- and Br- may reduce the BTEX removal efficiency of sulfate radical-based advanced oxidation process (SR AOP) and the presence of Cl- and Br- may even lead to the formation of toxic halogenated byproducts. PMID- 28992484 TI - Emerging contaminants in Indian environmental matrices - A review. AB - The emergence of issues related to environment from ECs is a topic under serious discussions worldwide in recent years. Indian scenario is not an exception as it is tremendously growing in its rate of production and consumption of compounds belongs to ECs categories. However, a comprehensive documentation on the occurrence of ECs and consequent ARGs as well as their toxic effects on vertebrates on Indian context is still lacking. In the present study, an extensive literature survey was carried out to get an idea on the geographical distribution of ECs in various environmental matrices (water, air, soil, sediment and sludge) and biological samples by dividing the entire subcontinent into six zones based on climatic, geographical and cultural features. A comprehensive assessment of the toxicological effects of ECs and the consequent antibiotic resistant genes has been included. It is found that studies on the screening of ECs are scarce and concentrated in certain geological locations. A total of 166 individual compounds belonging to 36 categories have been reported so far. Pharmaceuticals and drugs occupy the major share in these compounds followed by PFASs, EDCs, PCPs, ASWs and flame retardants. This review throws light on the alarming situation in India where the highest ever reported values of concentrations of some of these compounds are from India. This necessitates a national level monitoring system for ECs in order to assess the magnitude of environmental risks posed by these compounds. PMID- 28992485 TI - Reaction kinetics and mechanisms of organosilicon fungicide flusilazole with sulfate and hydroxyl radicals. AB - Flusilazole is an organosilane fungicide used for treatments in agriculture and horticulture for control of diseases. The reaction kinetics and mechanism of flusilazole with sulfate and hydroxyl radicals were studied. The rate constant of the radicals with the fungicide were determined by laser flash photolysis of peroxodisulfate and hydrogen peroxide. The results were 2.0 * 109 s-1M-1 for the reaction of the fungicide with HO and 4.6 * 108 s-1 M-1 for the same reaction with SO4- radicals. The absorption spectra of organic intermediates detected by laser flash photolysis of S2O82- with flusilazole, were identified as alpha aminoalkyl and siloxyl radicals and agree very well with those estimated employing the time-dependent density functional theory with explicit account for bulk solvent effects. In the continuous photolysis experiments, performed by photo-Fenton reaction of the fungicide, the main degradation products were: (bis(4-fluorophenyl)-hydroxy-methylsilane) and the non-toxic silicic acid, diethyl bis(trimethylsilyl) ester, in ten and twenty minutes of reaction, respectively. PMID- 28992486 TI - Emotion differentiation predicts likelihood of initial lapse following substance use treatment. AB - BACKGROUND: An estimated 40% to 70% of individuals treated for a substance use disorder relapse within one year following treatment (Walitzer and Dearing, 2006). Relapse is often driven by the need to cope with intense negative affect (Koob, 2013). Emotion differentiation, defined as the ability to distinguish among various emotion states, has been linked to better behavioral control in the face of negative affect (Kashdan et al., 2015). The aim of the current study was to determine if higher levels of emotion differentiation are associated with the risk of experiencing an initial lapse following entry into residential substance use treatment. METHODS: A total of 213 substance users (69.5% male, 94.4% African American, M age=43.01+/-11.35years) entering residential treatment were assessed on study variables at pre- and post-treatment, and at 1-, 3-, 6- and 12-month post-treatment. Emotion differentiation was calculated using ratings on five negative affect items derived from the Positive and Negative Affect Schedule (PANAS; Watson et al., 1988) at five assessment points. RESULTS: A Cox proportional-hazards regression model adjusting for age and negative affect intensity demonstrates that for every unit increase in emotion differentiation, there is a 27% reduction in the likelihood of initial lapse on any given day (OR=0.73; 95% CIs [0.56, 0.95]). CONCLUSIONS: The ability to differentiate among negative emotion states protects against initial lapse following treatment. PMID- 28992487 TI - AgNPs-decorated 3D printed PEEK implant for infection control and bone repair. AB - Polyetheretherketone (PEEK) is an ideal substitute material for bone tissue engineering, which can avoid the stress shielding phenomenon due to its similar mechanical properties to natural human bone. Complex bone defect and postoperative infection are still two enormous challenges in orthopedic clinics. It's well-known that additive manufacturing possesses the merits of high precision and rapid prototyping, thus it easily meets the needs of mold processing. In the present study, we developed a novel Ag-decorated 3D printed PEEK via catecholamine chemistry. SEM image showed that silver nanoparticles (AgNPs) were evenly anchored on the surface. The following antibacterial tests, including bacterial inhibition ring, bacterial dynamics curves and antibiofilm test, indicated that the Ag-decorated 3D PEEK scaffolds displayed significant antibacterial effect towards Gram-negative and Gram-positive bacteria. Then MG-63 cells were seeded on samples for cell proliferation and ALP activity tests. The results demonstrated the scaffold modified with AgNPs could support cell proliferation, and enhanced higher alkaline phosphatase activity compared with pure PEEK scaffold. Expectedly, this dual functional 3D material holds great potential application in clinical bone tissue repair. PMID- 28992488 TI - Hydroxyapatite functionalization to trigger adsorption and release of risedronate. AB - Bisphosphonates are widely employed drugs for the treatment of pathologies characterized by excessive bone resorption, and display a great affinity for apatitic supports. In this work we investigate how hydroxyapatite functionalization can influence the processes of adsorption and release of a bisphosphonate, namely risedronate. To this aim, pure hydroxyapatite (HA), hydroxyapatite with a partial substitution of Zn to Ca (ZnHA) and poly ethylenimine-functionalized hydroxyapatite (HAPEI) were submitted to interaction with risedronate solution. The results indicate that the mechanisms of adsorption and release are greatly influenced by the type of the apatitic support. All the apatitic supports display Langmuir isotherms for risedronate adsorption. However in the case of HAPEI the plateau is not reached even at high equilibrium concentrations in solution. The data suggest that risedronate adsorption on HAPEI mineral-organic support occurs not only through chemisorption on apatitic phase, as on HA and ZnHA, but also through physisorption involved by PEI coating, which modulates also bisphosphonate release. These properties of tailor-made hydroxyapatite supports could be exploited to develop delivery systems for antiresorptive agents directly on osteoporotic sites. PMID- 28992489 TI - Methotrexate induces high level of apoptosis in canine lymphoma/leukemia cell lines. AB - INTRODUCTION: Methotrexate is an antimetabolite used in the treatment of cancer and non-malignant diseases including rheumatoid arthritis, psoriasis and graft vs. host disease. Combination therapy with methotrexate was successful in the treatment of canine lymphoma, mammary tumor and invasive urinary bladder cancer. Lymphoma, the most common hematopoietic cancer in dogs, and leukemia are sensitive to chemotherapy, which is why methotrexate may be an important treatment option for these diseases. Although methotrexate is already used in veterinary oncology its effects on canine cancer cells has not been tested. The aim of the study was to evaluate for the first time methotrexate concentration dependent cytotoxicity and its capability of inducing apoptosis in selected canine lymphoma/leukemia cell lines: CLBL-1, GL-1 and CL-1 as a first step before the in vitro development of new therapeutic options with the use of methotrexate. RESULTS: Methotrexate exhibited concentration-dependent inhibitory effect on proliferation of all the examined cell lines with different degree of apoptosis induction. The most methotrexate sensitive cells belonged to CL-1 cell line derived from T cell neoplasia and previously characterized by high resistance to the majority of anticancer drugs used in the therapy of lymphoma/leukemia in dogs. Canine lymphoma and leukemia cell lines are sensitive to methotrexate, and this drug may be useful in effective treatment of canine neoplasms and especially of T-type leukemia/lymphoma. PMID- 28992490 TI - Does the presence of caffeine in the marine environment represent an environmental risk? A regional and global study. AB - Caffeine is an emerging contaminant considered to be an indicator of human contamination that has been widely detected in various aquatic systems, especially in continental waters. Nevertheless, the extent of its possible environmental impact is yet to be determined. This study determined the presence of caffeine, and evaluated the environmental hazard posed by this substance, in the "Rias Gallegas", a series of costal inlets in north-west Spain which are of great ecological value and in which fishing and bivalve farming, are a significant source of income. Caffeine was found to be present at concentrations higher than the limit of quantification (LOQ=3.07ngL-1) in 15 of the 23 samples analysed, with the highest seawater concentration being 857ngL-1 (the highest measured in seawater in Spain). Six out of 22 seawater samples resulted in a hazard quotient (HQ) from chronic exposure higher than 1 with the highest being 17.14, indicating a high probability of adverse effects in the aquatic environment. Environmental Exposure Distributions (EEDs) generated from a literature review of caffeine levels reported previously in four out of the five continents, showed that 28% of all seawater samples, and 69% of all estuary water samples where caffeine has ever been measured resulted in HQ>1 for chronic exposure. Further studies into the potential adverse effects that may arise from exposure to caffeine in aquatic systems are still required. Indeed, the need to gain a more in-depth understanding of the long-term ecotoxicological effects of caffeine is essential to ensure the quality of our health and environment. PMID- 28992491 TI - Photolysis of clethodim herbicide and a formulation in aquatic environments: Fate and ecotoxicity assessment of photoproducts by QSAR models. AB - The photochemical fate of the herbicide clethodim in natural waters was investigated under simulated and natural sunlight radiation. This herbicide exhibited a rapid degradation rate in simulated aquatic environment with half lives ranged from 27.9min to 4.6h. The commercial formulation of clethodim showed a faster degradation with half-lives from 19.3min to 1.4h. It has also been demonstrated that the photolytic behavior of clethodim was affected by the water composition and the radiation intensity. Nine major photoproducts were identified and their distribution was dependent on the experimental conditions. Photodegraded solutions of clethodim were shown to be more toxic to the bacteria Vibrio fischeri than the herbicide itself, reaching the maximum toxicity when the herbicide is completely degraded. QSAR analysis of the fate, ecotoxicological and physicochemical endpoints of the degradation products provided positive alerts for several identified by-products. Environmental fate and transport estimates showed that all photoproducts, unlike the active substance, are potential leachers. Moreover, predicted vapor pressures suggested that dermal contact and ingestion are the most probable exposure routes for workers and general population to both clethodim and its photoproducts. These results highlight the importance of the degradation products in attaining a complete knowledge of the fate and behavior of an herbicide in the environment. To our knowledge, this is the first study to report a detailed QSAR study on clethodim photoproducts under environmental conditions. These results provide a very valuable information that will guide further experimental studies leading to a better pesticide risk assessment. PMID- 28992492 TI - Tracing platinum accumulation kinetics in oyster Crassostrea gigas, a sentinel species in coastal marine environments. AB - Platinum Group Elements (PGEs) are extremely scarce in the Earth's Crust and of strong interest for high-end technologies due to their specific properties. They belong to the Technology Critical Elements (TCEs) for which use is forecast to increase, implying growing emissions into the environment in the following years. In particular, with the intensive use of platinum (Pt) in car catalytic converters, the anthropogenic geochemical cycle of this element has surpassed the natural cycle. Yet, environmental Pt levels are still in the sub picomolar range, making its analytical detection a challenge. Few studies cover the behavior of Pt in marine waters in terms of speciation, reactivity and possible transfer to the biota. In this study, oysters (Crassostrea gigas) from an unpolluted estuary were exposed to the stable isotope 194Pt in seawater at a range of concentrations during 35days. Seawater was renewed daily and spiked to three nominal Pt concentrations (50, 100, and 10,000ng.L-1) for two replicate series. In addition, control conditions were monitored. Five oysters from each tank were dissected after 3, 7, 14, 21, 28, 35days of Pt exposure, and analyzed by ICP-MS. Accuracy of this analytical method applied to biological matrix was checked by an inter method comparison with a voltammetrical technique. A concentration-dependent accumulation of Pt in oysters increasing with exposure time occurred. After 28days, oyster Pt accumulation from low and intermediate exposure conditions reached a plateau. This was not the case of the highest exposure condition for which oyster tissues showed increasing concentrations until the last day of the experiment. A linear correlation exists between seawater concentrations and Pt content in oysters for low and intermediate exposure concentrations i.e. closer to environmental concentrations. By showing high Pt accumulation potential, oysters may serve as sentinels, ensuring biomonitoring of Pt concentrations in marine coastal waters. PMID- 28992493 TI - Long-term impact of wildfire on soils exposed to different fire severities. A case study in Cadiretes Massif (NE Iberian Peninsula). AB - Wildfires affect ecosystems depending on the fire regime. Long-term studies are needed to understand the ecological role played by fire, especially as regards its impact on soils. The aim of this study is to monitor the long-term effects (18years) of a wildfire on soil properties in two areas affected by low and high fire severity regimes. The properties studied were total nitrogen (TN), total carbon (TC), C/N ratio, soil organic matter (SOM) and extractable calcium (Ca), magnesium (Mg), sodium (Na) and potassium (K). The study was carried out in three phases: short- (immediately after the wildfire), medium- (seven years after the wildfire) and long-term (18years after the wildfire). The results showed that in both fire regimes TN decreased with time, TC and SOM were significantly lower in the burned plots than they were in the control in the medium- and long-terms. C/N ratio was significantly lower at short-term in low wildfire severity area. Extractable Ca and Mg were significantly higher in control plot than in the burned plots in the medium-term. In the long-term, extractable Ca and Mg were significantly lower in the area exposed to a high severity burning. No differences were identified in the case of extractable Na between plots on any of the sampling dates, while extractable K was significantly higher in the plot exposed to low wildfire than it was in the control. Some restoration measures may be required after the wildfire, especially in areas affected by high severity burning, to avoid the long-term impacts on the essential soil nutrients of TC, SOM, extractable Ca and Mg. This long-term nutrient depletion is attributable to vegetation removal, erosion, leaching and post-fire vegetation consumption. Soils clearly need more time to recover from wildfire disturbance, especially in areas affected by high severity fire regimes. PMID- 28992494 TI - Rural settlements transition (RST) in a suburban area of metropolis: Internal structure perspectives. AB - Rural settlements transition (RST) is one of the most significant indices for understanding the phenomena of rural reconstruction and urban-rural transformation in China. However, a systematic overview of RST is missing, and there is a lack of evidence regarding its characteristics from the internal structure perspectives. In this paper, we systematically explore the RST regarding spatio-temporal change characteristics of internal structure, patterns and impacts on rural environment and development by using practical survey internal land-use data from 2005 to 2015. The results show that the temporal change characteristics of the internal structure of rural settlements demonstrate a tendency for housing land to decrease and other land-use types to increase. The spatial change characteristics reveal that the structure inclines to more complexity and diversity from an exurban area to an urban-rural fringe area. Based on this finding, we identify that rapid development of rural industrialization, more agglomerate and effective industrial land-use, and improved public infrastructure construction are the general RST patterns. Spatially, there exists a physical decay pattern in the exurban area, thereby resulting in the hollowing-out of rural industries and of the population. In addition, the extensive and disorderly pattern in the suburban area causes low efficiency output and serious environmental pollution. The RST pattern in the urban hinterland promoted the "men-environment" compatible development. The study concludes that regional differentiation in patterns and impacts are significant in the process of RST. Future adaptive strategies for rural settlements adjustment should be conducted according to regional characteristics, including socio-economic status, physical geography condition and economic location to improve the rural environmental sustainability. PMID- 28992496 TI - Micro-Raman and SEM-EDS analyses to evaluate the nature of salt clusters present in secondary marine aerosol. AB - Marine aerosol is a complex inorganic and organic chemistry system which contains several salts, mainly forming different type of salt clusters. Different meteorological parameters have a key role in the formation of these aggregates. The relative humidity (%RH), temperature, CO, SO2 and NOx levels and even the O3 levels can promote different chemical reactions giving rise to salt clusters with different morphology and sizes. Sulfates, nitrates and chlorides and even mixed chlorosulfates or nitrosulfates are the final compounds which can be found in environments with a direct influence of marine aerosol. In order to collect and analyze these types of compounds, the use of adequate samplers is crucial. In this work, salt clusters were collected thanks to the use of a self-made passive sampler (SMPS) installed in a 20th century historic building (Punta Begona Galleries, Getxo, Basque Country, Spain) which is surrounded by a beach and a sportive port. These salt clusters were finally analyzed directly by micro-Raman spectroscopy and Scanning Electron microscopy coupled to Energy Dispersive X-ray spectrometry (SEM-EDS). PMID- 28992495 TI - Application of enzyme-hydrolyzed cassava dregs as a carbon source in aquaculture. AB - As a kind of tropical agricultural solid waste, cassava dregs had become a thorny nonpoint source pollution problem. This study investigated the feasibility of applying cassava dregs as a substitute for sucrose in biofloc technology (BFT) systems. Three types of biofloc systems (using three different carbon sources sucrose (BFT1), cassava dregs (BFT2) and enzyme-hydrolyzed cassava dregs (BFT3) respectively), and the control were constructed in this experiment in 200L tanks with a C/N ratio of 20/1. The comparison of the water quality indicators (The total ammonia nitrogen (TAN), nitrite (NO2--N), nitrate (NO3--N), chemical oxygen demand (COD)), biofloc for the above four groups was performed, and the results indicated that BFT3 showed greater potential to the formation of biofloc, which was beneficial for the water quality control. So the shrimp survival rate was the highest and the feed conversion rate was the lowest in BFT3. Besides, the high throughput sequencing results showed that the relative abundance of heterotrophic bacteria in the top 30 dominant microbial communities in BFT3 was higher than those in BFT1 and BFT2 by 20.70% and 1.19%, respectively, which could decrease TAN to improve the water quality. Overall, the results had proved that the cassava dregs of enzymes hydrolysis could be used as an ideal and cheap carbon source in BFT. PMID- 28992497 TI - Rice straw-based biochar beads for the removal of radioactive strontium from aqueous solution. AB - Biochars from agricultural residues have recently attracted significant attention as adsorbents for purifying contaminated water and wastewater. In this study, the removal of strontium from aqueous solutions was investigated using rice straw based biochar (RSBC) beads in both batch and continuous fixed-bed column systems. The RSBC beads had negatively charged surfaces and exhibited a large surface area (71.53m2/g) with high micro-porosity. The synthesized beads showed a maximum adsorption capacity of 175.95mg/g at an initial strontium concentration of 10g/L at 35 degrees C and pH7. Furthermore, they showed a good selectivity toward strontium ions in the presence of competing ions such as Al3+, Mg2+, and K+. The effects of different operating conditions like flow rate and initial strontium concentration were investigated in the fixed-bed column reactor. The Thomas, Adams-Bohart, and Yoon-Nelson models were applied to the experimental data to predict the breakthrough curves using non-linear regression. Both the Thomas and the Yoon-Nelson models were appropriate for describing entire breakthrough curves under different operating conditions. Overall, RSBC beads demonstrate great potential as efficient adsorbents for the treatment of wastewater polluted with strontium in a continuous operation mode. PMID- 28992498 TI - Assessing bioavailability of complex chemical mixtures in contaminated soils: Progress made and research needs. AB - Understanding the distribution, behaviour and interactions of complex chemical mixtures is key for providing the evidence necessary to make informed decisions and implement robust remediation strategies. Much of the current risk assessment frameworks applied to manage land contamination are based on total contaminant concentrations and the exposure assessments embedded within them do not explicitly address the partitioning and bioavailability of chemical mixtures. These oversights may contribute to an overestimation of both the eco toxicological effects of the fractions and the mobility of contaminants. In turn, this may limit the efficacy of risk frameworks to inform targeted and proportionate remediation strategies. In this review we analyse the science surrounding bioavailability, its regulatory inclusion and the challenges of incorporating bioavailability in decision making process. While a number of physical and chemical techniques have proven to be valuable tools for estimating bioavailability of organic and inorganic contaminants in soils, doubts have been cast on its implementation into risk management soil frameworks mainly due to a general disagreement on the interchangeable use of bioavailability and bioaccessibility, and the associated methods which are still not standardised. This review focuses on the role of biotic and abiotic factors affecting bioavailability along with soil physicochemical properties and contaminant composition. We also included advantages and disadvantages of different extraction techniques and their implications for bioavailability quantitative estimation. In order to move forward the integration of bioavailability into site specific risk assessments we should (1) account for soil and contaminant physicochemical characteristics and their effect on bioavailability; (2) evaluate receptor's potential exposure and uptake based on mild-extraction; (3) adopt a combined approach where chemical-techniques are used along with biological methods; (4) consider a simplified and cost-effective methodology to apply at regulatory and industry setting; (5) use single-contaminant exposure assessments to inform and predict complex chemical mixture behaviour and bioavailability. PMID- 28992499 TI - Contributions of dioxins and furans to the urban sediment signature: The role of atmospheric particles. AB - Polychlorinated dibenzo-p-dioxins (PCDD) and polychlorinated dibenzo-p-furans (PCDF) are widely distributed in the environment. The diverse production processes that form these compounds lead to a range of chemical signatures although weathering may cause changes to these signature over time and with increasing distance from their origin. Chemical signatures in sediments based on 17 PCDD/Fs were developed in Concepcion, a Chilean city in the middle of a complex hydrological system which contains several small urban freshwater bodies and the River Bio-Bio. The region has numerous industrial and domestic activities that may contribute PCDD/Fs to the environment. Sediments from urban lakes had higher concentrations of dioxins and furans (mean=941ng.kg-1) than either a remote lake (335ng.kg-1) located 32km from the city or marine samples (mean=124ng.kg-1). Up to 85% of the compounds present in all sediment samples could be explained by the chemical signature associated with airborne particulates leaving only 15-30% of the chemical signature potentially arising from other sources. The remote lake had higher proportions of the less chlorinated compounds compared to the urban samples. PMID- 28992500 TI - Plastic bag and facial cleanser derived microplastic do not affect feeding behaviour and energy reserves of terrestrial isopods. AB - Current data regarding the effects of microplastic (MP) on terrestrial organisms are very scarce. Isopods play an important role in plant litter decomposition processes and are commonly used test species in terrestrial ecotoxicity studies. Their altered feeding behaviour and energy reserves are established biomarkers of adverse effects upon stressor exposure. For this study we assessed the effects of MP derived from plastic bag film (mean size 183+/-93MUm) and particles from a facial cleanser (mean size 137+/-51MUm) on the terrestrial isopod, Porcellio scaber. Isopods were exposed to MP via feeding on food pellets (4mgg-1 dry weight; 0.4% w w-1) for 14days under laboratory conditions. A control group was exposed to food pellets with no MP added. In line with previously suggested modes of MP action on animal ingestion, we assessed the food ingestion rate, defecation rate, food assimilation rate and efficiency, body mass change, mortality and energy reserves (proteins, carbohydrates, and triglycerides) in the digestive glands (hepatopancreas) of individual isopods. Contrary to our expectations, no effects on either end-point were observed under the given exposure conditions. Further work should be carried out to investigate the potential longer-term effects of such exposure. We conclude that 14days exposure to plastic bag and facial cleanser MP is not severely hazardous to isopods. PMID- 28992501 TI - The new Green Revolution: Sustainable intensification of agriculture by intercropping. AB - Satisfying the nutritional needs of a growing population whilst limiting environmental repercussions will require sustainable intensification of agriculture. We argue that intercropping, which is the simultaneous production of multiple crops on the same area of land, could play an essential role in this intensification. We carried out the first global meta-analysis on the multifaceted benefits of intercropping. The objective of this study was to determine the benefits of intercropping in terms of energetic, economic and land sparing potential through the framework of the stress-gradient hypothesis. We expected more intercropping benefits under stressful abiotic conditions. From 126 studies that were retrieved from the scientific literature, 939 intercropping observations were considered. When compared to the same area of land that was managed in monoculture, intercrops produced 38% more gross energy (mean relative land output of 1.38) and 33% more gross incomes (mean relative land output of 1.33) on average, whilst using 23% less land (mean land equivalent ratio of 1.30). Irrigation and the aridity index in non-irrigated intercrops did not affect land equivalent ratio, thereby indicating that intercropping remains beneficial, both under stressful and non-stressful contexts concerning moisture availability. Fertilisation and intercropping patterns (rows and strips vs. mixed) did not affect land equivalent ratio. Although intercropping offers a great opportunity for intensification of existing agricultural lands, many challenges need to be tackled by experts from multiple disciplines to ensure its feasible implementation. PMID- 28992502 TI - Tomography of anthropogenic nitrate contribution along a mesoscale river. AB - Elevated nitrate concentrations are a thread for water supply and ecological integrity in surface water. Nitrate fluxes obtained by standard monitoring protocols at the catchment outlet strongly integrate spatially and temporally variable processes such as mobilization and turnover. Consequently, inference of dominant nitrate sources is often problematic and challenging in terms of effective river management and prioritization of measures. Here, we combine a spatially highly resolved assessment of nitrate concentration and fluxes along a mesoscale catchment with four years of monitoring data at two representative sites. The catchment is characterized by a strong land use gradient from pristine headwaters to lowland sub-catchments with intense agricultural land use and wastewater sources. We use nitrate concentrations in combination with hydrograph separation and isotopic fingerprinting methods to characterize and quantify nitrate source contribution. The hydrological analysis revealed a clear dominance of base flow during both campaigns. However, the absolute amounts of discharge differed considerably from one another (outlet: 1.42m3s-1 in 2014, 0.43m3s-1 in 2015). Nitrate concentrations are generally low in the pristine headwaters (<3mgL 1) and increase downstream (15 to 16mgL-1) due to the contribution of agricultural and wastewater sources. While the agricultural contribution did not vary in terms of nitrate concentration and isotopic signature between the years, the wastewater contribution strongly increased with decreasing discharge. Wastewater-borne nitrate load in the entire catchment ranged between 19% (2014) and 39% (2015). Long-term monitoring of nitrate concentration and isotopic composition in two sub-catchment exhibits a good agreement with findings from spatially monitoring. In both datasets, isotopic composition indicates that denitrification plays only a minor role. The spatially highly resolved monitoring approach helped to pinpoint hot spots of nitrate inputs into the stream while the long-term information allowed to place results into the context of intra-annual variability. PMID- 28992503 TI - The effect of operational parameters on the biodegradation of bisphenols by Trametes versicolor laccase immobilized on Hippospongia communis spongin scaffolds. AB - Due to the rapid growth in quantities of phenolic compounds in wastewater, the development of efficient and environmentally friendly methods for their removal becomes a necessity. Thus, in a presented work, for the first time, a novel material, Hippospongia communis spongin-based scaffold, was used as a biopolymeric support for the immobilization of laccase from Trametes versicolor. The resulting biocatalytic systems were used for the biodegradation of three bisphenols: bisphenol A (BPA), bisphenol F (BPF) and bioremoval-resistant bisphenol S (BPS). Optimization of the immobilization and biodegradation methodologies was performed to increase bisphenols removal. The effect of temperature, pH and initial pollutant concentration was evaluated. It was shown that under optimal conditions, almost 100% of BPA (pH5, 30 degrees C) and BPF (pH5, 40 degrees C), and over 40% of BPS (pH4, 30 degrees C) was removed from the solution at a concentration of 2mg/mL. Furthermore, the immobilized laccase exhibited good reusability and storage stability, retaining over 80% of its initial activity after 50days of storage. In addition, the main biodegradation products of BPA and BPF were identified. It was shown that mainly dimers and trimers were formed following the oxidation of bisphenols by the immobilized laccase. PMID- 28992504 TI - Benefits of adding forestry clearance residues for the soil and vegetation of a Mediterranean mountain forest. AB - Desertification is occurring throughout the mountainous areas of the Mediterranean. These processes lead to reduced soil fertility, increased soil loss, and reduced vegetation cover and species richness. To prevent further damage, it is recommendable to use low-cost approaches that are compatible with the European Strategy of Circular Economy guidelines. We investigated the systemic benefits from recycling of forest clearance residue by adding it to a dry Mediterranean mountainous area. More specifically, we performed afforestation without addition of residue in two control plots (C plots), and afforestation with addition of 10Mgha-1 of clearance residue from a nearby region dominated by Aleppo pine (Pinus halepensis Mill.) in two other plots (PM plots). We conducted the experiments throughout 30months after the afforestation process. Eighteen months after the intervention, the PM plots had significant increases in the soil organic carbon (SOC), and related increases in ecosystem productivity and stability. More generally, addition of clearance residues improved soil and vegetation recovery, and contributed to more successful afforestation. The improvements may be explained by an increase of infiltration process due to the physical changes in the soil following bio-waste addition. Addition of the forest residues increased the formation of soil macrochannels, and also increased the sink area, thereby improving the hydrodynamics of the ecosystem. Thus, soil loss was reduced by 98.2% in the PM plots relative to the C plots. Our study indicates that application of forest clearance residues to Mediterranean mountainous areas is an effective land management practice that produces very little waste, and it is in accordance with European policy. PMID- 28992505 TI - Sorption of ionic and nonionic organic solutes onto giant Miscanthus-derived biochar from methanol-water mixtures. AB - The sorption of naphthalene (NAP) and 1-naphthoic acid (1-NAPA) onto giant Miscanthus-derived biochar was investigated in methanol volume fractions (fc) of 0-0.6 as a function of ionic composition (5mM CaCl2 and 10mM KCl) and liquid pH (2 and 7). The sorption onto biochar was nonlinear with 0.42<=N<=0.95; thus, a concentration-specific sorption constant (Km) was compared. The Km log linearly decreased with increasing fc, except for 1-NAPA from a CaCl2 mixture at pH7. Isotherm data was fitted with a cosolvency sorption model through which the slope (alphasigma) of the inverse log linear Km-fc plot and empirical constant (alpha) were obtained. NAP sorption was well described by the cosolvency model with the alpha value being 0.41-0.53, indicating a methanol-biochar interaction favoring more sorption than the cosolvency based prediction. In particular, the slope (alphasigma) of 1-NAPA was lower than that of NAP, indicating less reduction of 1 NAPA sorption (i.e., lower alpha value) by methanol. In comparison with other sorbents, the alpha value was approximately intermediate between a humic substance and kaolinite clay. An analysis of FT-IR spectra suggested the transformation of O-containing functional groups by methanol, which will subsequently boost the pi-pi interaction between an organic solute and biochar. Moreover, Ca2+-induced sorption between anionic 1-NAPA and a negatively charged biochar surface was also fortified in the methanol mixture. The results revealed unexplored cosolvent effects on organic solute sorption onto biochar and identified the hydrophobic and hydrophilic sorption moieties of biochar as affected by the cosolvent. PMID- 28992506 TI - Organic speciation of ambient quasi-ultrafine particulate matter (PM0.36) in Augsburg, Germany: Seasonal variability and source apportionment. AB - To investigate the organic composition and their sources of very fine atmospheric particulate matter (PM), size-segregated PM was sampled using rotating drum impactor (RDI) in series with a sequential filter sampler in Augsburg, Germany, from April 2014 to February 2015. Organic speciation analysis and organic carbon/elemental carbon (OC/EC) analysis was performed for the smallest size fraction PM0.36 (PM<360nm). Different OC fractions were determined by thermal optical EC/OC analyzer, and OC2, OC3 and OC4 refer to OC fractions that were derived at 280, 480 and 580 degrees C, respectively. Positive matrix factorization (PMF) analysis was applied for source apportionment study. PMF resolved 5 sources including biogenic dominated secondary organic aerosol (bioSOA), isoprene dominated SOA (isoSOA), traffic, biomass burning (BB) and biomass burning originated SOA (bbSOA). On annual average, PMF results indicate the largest contribution of biogenic originated SOA (bioSOA plus isoSOA) to OC, followed by traffic and then BB related sources (BB plus bbSOA). Traffic was found to be associated with the smallest particles; whereas bioSOA and BB are associated with larger particles. Secondary organic marker compounds from biogenic precursors, OC2, OC3 and bioSOA, isoSOA source factors show summer maximum. Polycyclic aromatic hydrocarbons (PAHs), biomass burning markers, OC4 and BB, bbSOA source factors show winter maximum. Hopanes and the traffic source factor show little seasonal variation. Summer peaks of OC3 and OC2 are well modeled by PMF and are attributed mainly to biogenic SOA. OC4 was generally poorly modeled due to lack of characteristic low volatile markers. Summer maxima of biogenic SOA related compounds and source factors are positively correlated with temperature, global radiation, O3 concentration and mixing layer height (MLH). Winter maxima of BB related compounds and source factors are negatively correlated with temperature and MLH; whereas positively correlated with NO2 level. PMID- 28992507 TI - Antimicrobial edible coatings and films from micro-emulsions and their food applications. AB - This study focused on the use of antimicrobial edible coatings and films from micro-emulsions to reduce populations of foodborne pathogens in foods. Corn-Bio fiber gum (C-BFG) was used as an emulsifier with chitosan. Allyl isothiocyanate (AIT) and lauric arginate ester (LAE) served as antimicrobials. Micro-emulsions were obtained from a solution consisting of 1% chitosan, 0.5% C-BFG, and 1-4% AIT or LAE which was subject to high pressure homogenization (HPH) processing at 138MPa for 3cycles. Coatings and films produced from the micro-emulsions had micro-pores with sizes ranging from 100 to 300nm and micro-channels that hold antimicrobials effectively and facilitate the release of antimicrobials from the center to the surface of the films or coatings, thus enhancing their antimicrobial efficacy. The coatings and films with 1% AIT reduced populations of Listeria innocua by over 5, 2, and 3 log CFU in culture medium (Tryptic soy broth, TSB), ready-to-eat meat, and strawberries, respectively. The coatings and films with 1% LAE reduced populations of Escherichia coli O157:H7 and Salmonella spp. by over 5 and 2 log CFU in TSB and strawberries, respectively. This study provides an innovative approach for the development of effective antimicrobial materials to reduce food borne pathogenic contaminants on ready-to-eat meat, strawberries, or other food. PMID- 28992508 TI - IL-37 and 38 signalling in gestational diabetes. AB - Gestational diabetes mellitus (GDM) is still a clinical challenge around world. Inflammation contributes to the pathogenesis of GDM, the precise underlying mechanism remains to be explored. IL-37 and 38 play important role in autoimmunity, but their role in the development of GDM is unclear. Using histopathology and immunohistochemistry, the thickness of the umbilical artery, the area of capillaries within the placental chorionic villi, and the production of IL-37/38 were determined. Placental mRNA of IL-37/IL-38 from GDM and Non-GMD was measured using qRT-PCR. serum IL-37/IL38 levels were evaluated, using ELISA. IL-37 was reduced 49%, 48% or 57% in chorionic villi of placentas (P<0.05), umbilical artery (P<0.05), or umbilical vein (P<0.05) from GDM women, respectively, compared to that from non-GDM women. In contrast, IL-38 was increased 3.3, 2.6, or 2.6 fold in chorionic villi (P<0.01), umbilical artery (P<0.05), umbilical vein (P<0.05) from GDM women, respectively, compared to that from non-GDM women. IL-37 in GDM placentas or serum was reduced ~52% or 33%, compared to that from Non-GDM subjects, respectively; whereas IL-38 in the GDM placentas or serum was increased by 1.6 fold or 1.3 fold, compare to that from Non-GDM, respectively. Our data suggest that IL-37 protect pregnant women from the development of GDM. IL-38 produced in the chorionic villi and umbilical cords may be a response to local inflammation during the development of GDM. Such a dysregulated micro-environment may contribute to the development of GDM via an immune-mediated mechanism. These data may provide useful information for the intervention for GDM. PMID- 28992510 TI - Three-dimensional piezoelectric fibrous scaffolds selectively promote mesenchymal stem cell differentiation. AB - The discovery of electric fields in biological tissues has led to efforts in developing technologies utilizing electrical stimulation for therapeutic applications. Native tissues, such as cartilage and bone, exhibit piezoelectric behavior, wherein electrical activity can be generated due to mechanical deformation. Yet, the use of piezoelectric materials have largely been unexplored as a potential strategy in tissue engineering, wherein a piezoelectric biomaterial acts as a scaffold to promote cell behavior and the formation of large tissues. Here we show, for the first time, that piezoelectric materials can be fabricated into flexible, three-dimensional fibrous scaffolds and can be used to stimulate human mesenchymal stem cell differentiation and corresponding extracellular matrix/tissue formation in physiological loading conditions. Piezoelectric scaffolds that exhibit low voltage output, or streaming potential, promoted chondrogenic differentiation and piezoelectric scaffolds with a high voltage output promoted osteogenic differentiation. Electromechanical stimulus promoted greater differentiation than mechanical loading alone. Results demonstrate the additive effect of electromechanical stimulus on stem cell differentiation, which is an important design consideration for tissue engineering scaffolds. Piezoelectric, smart materials are attractive as scaffolds for regenerative medicine strategies due to their inherent electrical properties without the need for external power sources for electrical stimulation. PMID- 28992509 TI - Liposomes-coated gold nanocages with antigens and adjuvants targeted delivery to dendritic cells for enhancing antitumor immune response. AB - For nanovaccine-based cancer immunotherapy, dendritic cells (DCs) are one of the most powerful antigen presenting cells (APCs) that initiate and promote the maturation of antigen-specific cytotoxic T lymphocytes (e.g., CD8+ T cells) to induce the local and systemic antitumor immunity and further suppress the tumor metastasis and produce long-term protection against tumor. Thus, the activation and maturation of DCs is the prerequisite for efficient CD8+ T cell-based antitumor immune responses, which is considered as a primary and promising task for nanovaccine engineering. Herein, we introduce a versatile nanovaccine of liposomes-coated gold nanocages (Lipos-AuNCs) modified with DCs specific antibody aCD11c for targeted delivery of adjuvant MPLA and melanoma antigen peptide TRP2 to promote the activation and maturation of DCs, and enhance tumor specific T lymphocytes responses. Moreover, AuNCs accumulation and AuNCs-engulfed DCs migration to regional lymph nodes (RLNs) became real-time visualization through in vivo fluorescence and photoacoustic (PA) imaging to monitor the immunity process. In vivo experimental results demonstrated that the targeted antigen/adjuvants-loaded AuNCs exhibited enhanced antitumor immune response to inhibit tumor growth and metastasis in both B16-F10 prophylactic and lung metastasis models, which may act as a promising nanoplatform for antitumor immunotherapy and in vivo tracking. PMID- 28992512 TI - Predictors of having a first child taken into care at birth: A population-based retrospective cohort study. AB - The objective of this study is to determine which maternal events and diagnoses in the two years before childbirth are associated with higher risk for having a first child taken into care at birth by child protection services. A population based retrospective cohort of women whose first child was born in Manitoba, Canada between 2002 and 2012 and lived in the province at least two years before the birth of their first child (n=53,565) was created using linkable administrative data. A logistic regression model determined the adjusted odds ratios (AOR) of having a child taken into care at birth. Characteristics having the strongest association with a woman's first child being taken into care at birth were mother being in care at the birth of her child (AOR=11.10; 95% CI=8.38 14.71), substance abuse (AOR=8.94; 95% CI=5.08-15.71), schizophrenia (AOR=6.69; 95% CI=3.89-11.52) developmental disability (AOR=6.45; 95% CI=2.69-14.29), and no prenatal care (AOR=5.47; 95% CI=3.56-8.41). Most characteristics of women deemed to be at high risk for having their child taken into care at birth are modifiable or could be mitigated with appropriate services. PMID- 28992511 TI - Plant mitochondrial membranes: adding structure and new functions to respiratory physiology. AB - The membranes of mitochondria are focal points of cellular physiology and respiratory energy transformation. Recent discoveries have started painting a refined picture of plant mitochondrial membranes as platforms in which structure and function have evolved in an interconnected and dynamically regulated manner. Hosting ancillary functions that interact with other mitochondrial properties gives mitochondria the characteristics of multitasking and integrated molecular mega machines. We review recent insights into the makeup and the plasticity of the outer and inner mitochondrial membranes, their intimate relationship with respiratory function and regulation, and their properties in mediating solute transport. Synthesizing recent research advances we hypothesize that plant mitochondrial membranes are a privileged location for incorporation of a wide range of processes, some of which collaborate with respiratory function, including plant immunity, metabolic regulation and signal transduction, to underpin flexibility in the acclimation to changing environments. PMID- 28992513 TI - Evaluation of second step child protection videos: A randomized controlled trial. AB - This randomized controlled trial (RCT) examined the effects of the Second Step Child Protection Unit videos on parents' knowledge, motivation, and self-reported communication with their child about personal safety and childhood sexual abuse prevention. Parents of children between the ages of 3-11 years were randomly assigned to the intervention (watching the Second Step videos) or the control (watching videos on child obesity) groups. They completed measures assessing their knowledge of child sexual abuse (CSA), motivation to discuss CSA, self reported discussions of CSA, child history of victimization, parent exposure to CSA, and comparable measures on topics of health and nutrition at pre-test. Participants viewed the videos one week later and immediately completed post-test 1, and then two months later completed the measures again. Multivariate Analyses of Covariance (MANCOVAs) and serial mediation analyses were conducted with the final sample of 438. The intervention group, compared to the control group, had significant increases in knowledge (specifically, less restrictive stereotype beliefs about CSA) and motivation to talk with their children about CSA both immediately after the intervention and at the two-month follow-up. Although the intervention did not have a direct effect on parent self-reported conversations with their children about CSA, it had a mediated effect. The intervention increased knowledge regarding CSA, which then predicted motivation, which in turn predicted conversations. The most pronounced effect was the intervention's direct effect of increasing motivation immediately after the intervention, which then increased self-reported conversations with children about personal safety and CSA two months later. PMID- 28992514 TI - Profile of and expenditure on morbidity and hospitalizations among elderly Analysis of a nationally representative sample survey in India. AB - INTRODUCTION: Understanding morbidity pattern and associated expenditure is essential for implementation of appropriate healthcare and social security measures for the elderly. This study aims to assess the proportion of ailing persons (PAP) in the last 15days, the utilization of hospitalization services in the last 365days and the expenditure incurred for hospitalizations among the elderly in India. METHODS: This study analysed data from a nationally representative survey by the National Sample Survey Office (NSSO) in 2014-15 on 36,480 rural and 29,452 urban households. Distribution of morbidity and in patient health care utilisation were analysed by subgroups of sex, residence, wealth quintile and type of health care provider. All estimates were weighted to account for the complex sampling design. RESULTS & DISCUSSION: Among 27,245 elderly persons, 30.3% reported having suffered an ailment in the past 15days and 8% reported at least one hospitalisation episode in the last 365days. All quintiles, except the lowest, utilized private sector more than the public sector for hospitalisations. The distribution of PAP (Concentration Index (CI)=+0.11; +0.07,+0.15) and the utilization of hospitalisation services (CI=+0.18; +0.11,+0.25) were found to be significantly pro-rich. The median (IQR) expenditure on hospitalization was INR 7370 (2600, 18,060). The wealthiest quintile spent 3.1 times more than the poorest quintile on hospitalisation. CONCLUSION: Efforts to reduce inequity among elderly persons in health status and healthcare utilization should be integral to any strategy targeting achievement of third sustainable development goal- "ensuring healthy lives and promoting well being for all at all ages". PMID- 28992515 TI - Molecular characterization of diarrheagenic Escherichia coli isolated from vegetables in Argentina. AB - The aim of this study was to investigate the prevalence of diarrheagenic E. coli strains in vegetables from the humid Pampa region, Argentina, and to determine the occurrence of serotypes and virulence genes in the isolates. A total of 373 fresh vegetable samples obtained from 41 different geographical points were examined. E. coli was detected in 38.6% of the samples. Ten isolates could be obtained from 14 samples presumptively positive for diarrheagenic E. coli: 8 were identified as atypical Enteropathogenic E. coli (aEPEC) and 2 as Verocytotoxigenic E. coli (VTEC). Lettuce and beet were the vegetables most frequently contaminated with pathogenic E. coli. The isolates belonged to serotypes O1:H7, O28:H19, O39:H40, O86:H31, O132:H8, O139:H20, O178:H7 and O178:H19, some of which reportedly have caused human illness, and one isolate resulted non typeable. Taking into account the distribution of 16 nle genes, 7 profiles were detected. On the other hand, all tested isolates harbored the gene encoding for the adhesin HcpA. Other adhesion related genes were also identified: ecpA and elfA were detected in 90%, lpfA0113 in 60%, and ehaA in 50% of the isolates meanwhile ihaA was only observed in O178:H19 isolate. This VTEC isolate harbored, also, Cdt-V toxin and megaplasmid encoding genes such as espP, subA and epeA and exhibited a strong cytotoxic effect. These data is the first molecular E. coli report that confirms the presence of E. coli pathotypes circulating among vegetables in Argentina. Genetic characterization showed that in addition to eae or vtx genes, isolates obtained from vegetables harbored genes encoding other toxins, adhesins, and components related to the type III secretion system that could contribute to their virulence. In conclusion, this research shows that vegetables in Argentina may be the source of VTEC and EPEC infections in the community and therefore, they should be considered as vehicles for transmission of these potentially pathogenic bacteria. PMID- 28992516 TI - Production of the Sicilian distillate "Spiritu re fascitrari" from honey by products: An interesting source of yeast diversity. AB - The "Spiritu re fascitrari" (SRF) is a typical Sicilian distillate obtained from the by-products of traditional process of honey production. Although some alcoholic fermentation of honey based products have been described, the present research represents the first investigation on the yeast ecology and the physico chemical characteristics of honey by-products subjected to an alcoholic fermentation followed by distillation. All samples collected during manufacturing process were analysed for the count of total, osmophilic and osmotolerant yeasts. The honeycombs and equipment surfaces showed the presence of yeasts that was 1.7 and 1.1 Log (CFU/mL), respectively. After enrichment, yeast populations increased and a significant increase of yeasts was registered during the alcoholic fermentation (AF), reaching loads higher than 7LogCFU/mL after day 6. A total of 2816 colonies of yeasts were isolated from the count plates and the following species were genetically identified: Lachancea fermentati, Pichia anomala, Pichia kudriavzevii, Saccharomyces cerevisiae, Wickerhamomyces anomalus, Zygosaccharomyces bailii and Zygosaccharomyces rouxii. During the spontaneous AF process, the species S. cerevisiae, Z. bailii and Z. rouxii were mainly isolated and the feed conversion ratio of sugars into ethanol was about 53%; high contents of acetic acid and glycerol were also found. The highest concentrations of volatile organic compounds (VOCs) were registered for esters, alcohols and aldehydes (346.55, 331.041 and 13.65MUg/L, respectively). Many VOCs identified as "specific floral markers" such as nonanal and 1-hexanol, 1-octanal and linalool oxide were found. Although more studies are needed, our results suggested that the S. cerevisiae strains isolated in this study must be evaluated in situ for their potential to act as starters for the continuous production of SRF. This because these strains are expected to drive the fermentation process reducing the risk of off-odour and off-flavour formation. PMID- 28992517 TI - Application of next generation sequencing toward sensitive detection of enteric viruses isolated from celery samples as an example of produce. AB - Next generation sequencing (NGS) holds promise as a single application for both detection and sequence identification of foodborne viruses; however, technical challenges remain due to anticipated low quantities of virus in contaminated food. In this study, with a focus on data analysis using several bioinformatics tools, we applied NGS toward amplification-independent detection and identification of norovirus at low copy (<103 copies) or within multiple strains from produce. Celery samples were inoculated with human norovirus (stool suspension) either as a single norovirus strain, a mixture of strains (GII.4 and GII.6), or a mixture of different species (hepatitis A virus and norovirus). Viral RNA isolation and recovery was confirmed by RT-qPCR, and optimized for library generation and sequencing without amplification using the Illumina MiSeq platform. Extracts containing either a single virus or a two-virus mixture were analyzed using two different analytic approaches to achieve virus detection and identification. First an overall assessment of viral genome coverage for samples varying in copy numbers (1.1*103 to 1.7*107) and genomic content (single or multiple strains in various ratios) was completed by reference-guided mapping. Not unexpectedly, this targeted approach to identification was successful in correctly mapping reads, thus identifying each virus contained in the inoculums even at low copy (estimated at 12 copies). For the second (metagenomic) approach, samples were treated as "unknowns" for data analyses using (i) a sequence-based alignment with a local database, (ii) an "in-house" k-mer tool, (iii) a commercially available metagenomics bioinformatic analysis platform cosmosID, and (iv) an open-source program Kraken. Of the four metagenomics tools applied in this study, only the local database alignment and in-house k-mer tool were successful in detecting norovirus (as well as HAV) at low copy (down to <103 copies) and within a mixture of virus strains or species. The results of this investigation provide support for continued investigation into the development and integration of these analytical tools for identification and detection of foodborne viruses. PMID- 28992518 TI - Comprehensive detection of viruses in pediatric patients with acute liver failure using next-generation sequencing. AB - BACKGROUND: Pediatric acute liver failure (PALF) is a rare and severe syndrome that frequently requires liver transplantation. Viruses are one of the most frequent causes of this disease, however, pathogenic viruses are not determined in many patients. Recently next-generation sequencing (NGS) has been applied to comprehensively detect pathogens of infectious diseases of unknown etiology. OBJECTIVES: To evaluate an NGS-based approach for detecting pathogenic viruses in patients with PALF or acute hepatitis of unknown etiology. STUDY DESIGN: To detect virus-derived DNA and RNA sequences existing in sera/plasma from patients, both DNA and RNA sequencing were performed. First, we validated the ability of NGS to detect viral pathogens in clinical serum/plasma samples, and compared different commercial RNA library preparation methods Then, serum/plasma of fourteen patients with PALF or acute hepatitis of unknown etiology were evaluated using NGS. RESULTS: Among three RNA library preparation methods, Ovation RNA-Seq System V2 had the highest sensitivity to detect RNA viral sequences. Among fourteen patients, sequence reads of torque teno virus, adeno-associated virus, and stealth virus were found in the sera of one patient each, however, the pathophysiological role of these three viruses was not clarified. Significant virus reads were not detected in the remaining 11 patients. CONCLUSIONS: This finding might be due to low virus titer in blood at the time of referral or a non infectious cause might be more frequent. These results suggest an NGS-based approach has potential to detect viral pathogens in clinical samples and would contribute to clarification of the etiology of PALF. PMID- 28992519 TI - Posterior atlantoaxial fusion with a screw-rod system: Allograft versus iliac crest autograft. AB - OBJECTIVE: To compare the effectiveness of allograft and iliac crest autograft in atlantoaxial fusion. PATIENTS AND METHODS: Between January 2012 and December 2012, 41 consecutive patients underwent posterior atlantoaxial fusion with a screw-rod fixation system in our spine center. The choice to use allograft or iliac crest autograft was made by the patient himself or herself after being informed about the advantages and disadvantages of both methods. In the allograft group, we used mixed material of morcellized demineralized freeze-dried bone allograft and local autograft for posterior atlantoaxial fusion. In the autograft group, we used the morcellized iliac crest autograft for fusion. Patients underwent regular follow up including CT scans and dynamic radiographs 6 months postoperatively and every 6 months thereafter until study completion or confirmation of fusion. RESULTS: Twenty-four patients underwent posterior atlantoaxial fusion with allograft, and 17 underwent fusion with autograft. All patients were followed up for at least 24 months. At the final follow-up visit, only two (8.3%) patients in the allograft group had confirmed posterior bony fusion on CT imaging while 15 (88.2%) patients in the autograft group had confirmed posterior bony fusion. None of the 41 patients had movement on the dynamic radiographs. CONCLUSIONS: Allograft is not reliable for posterior atlantoaxial fusion even with the rigid internal fixation of modern constructs. Autograft remains the first choice for atlantoaxial fusion despite the donor-site morbidity. The assessment of fusion based on a lack of movement on dynamic radiographs is not reliable. The confirmation of fusion should be based on the presence of bridging bone on CT imaging. PMID- 28992520 TI - Native and introduced squirrels in Italy host different Cryptosporidium spp. AB - The present study was undertaken to describe Cryptosporidium spp. infection in tree squirrels from 17 locations in Northern Italy. A total of 357 squirrels were examined, including species native to Europe (Sciurus vulgaris; n=123), and species introduced from North America (Sciurus carolinensis; n=162) and Southeast Asia (Callosciurus erythraeus; n=72). Faecal samples of all squirrels were examined for the presence of Cryptosporidium infection by microscopy (flotation method) and PCR/sequence analysis of the Cryptosporidium 18S rRNA, actin, and gp60 genes. Despite the overlapping ranges of native and introduced tree squirrel species in the study area, they host different Cryptosporidium spp. Sciurus vulgaris were exclusively infected with Cryptosporidium ferret genotype (n=13) belonging to three novel gp60 subtypes, VIIIb-VIIId. Sciurus carolinensis hosted C. ubiquitum subtype XIIb (n=2), Cryptosporidium skunk genotype subtype XVIa (n=3), and chipmunk genotype I subtype XIVa (n=1). Cryptosporidium chipmunk genotype I subtype XIVa was also found in two C. erythraeus. Comparing data from this and previous studies, we propose that Cryptosporidium skunk genotype and possibly C. ubiquitum subtype XIIb were introduced to Europe with eastern grey squirrels. Cryptosporidium chipmunk genotype I and ferret genotype were associated with high intensity infections, but there was no association with diarrhoea. PMID- 28992521 TI - Morphology and phylogeny of the testate amoebae Euglypha bryophila Brown, 1911 and Euglypha cristata Leidy, 1874 (Rhizaria, Euglyphida). AB - The genus Euglypha contains the largest number of filose testate amoeba taxa which were mainly described based on the morphological characteristics of shells. Despite the increasing amount of molecular data, the phylogenetic relationships within the genus Euglypha remain unresolved. In this work we provide new data on SSU rRNA gene sequences, light and electron microscopy for the two euglyphid species Euglypha bryophilaBrown, 1911 and Euglypha cristataLeidy, 1874. Both species are characterised by the presence of a turf of spines on the aboral pole of the shells but differ in shell cross sections (elliptical and circular, respectively). A newly revealed feature of E. bryophila is a three-lobed thickening at the anterior margin and an elongated lobe at the posterior margin of apertural plates. The phylogenetic analysis shows that the species group together with the previously sequenced taxa of the genus Euglypha according to the shell cross-section. The subdivision of the genus based on the shell symmetry may reflect evolutionary trends to complication of the shell from radial to biradial symmetry. We also suggest that the shape of the anterior thickening of apertural plates and the lobe at the posterior margin can be used to distinguish Euglypha at the species level. PMID- 28992522 TI - What is the optimum sample size for the study of peatland testate amoeba assemblages? AB - Testate amoebae are widely used in ecological and palaeoecological studies of peatlands, particularly as indicators of surface wetness. To ensure data are robust and comparable it is important to consider methodological factors which may affect results. One significant question which has not been directly addressed in previous studies is how sample size (expressed here as number of Sphagnum stems) affects data quality. In three contrasting locations in a Russian peatland we extracted samples of differing size, analysed testate amoebae and calculated a number of widely-used indices: species richness, Simpson diversity, compositional dissimilarity from the largest sample and transfer function predictions of water table depth. We found that there was a trend for larger samples to contain more species across the range of commonly-used sample sizes in ecological studies. Smaller samples sometimes failed to produce counts of testate amoebae often considered minimally adequate. It seems likely that analyses based on samples of different sizes may not produce consistent data. Decisions about sample size need to reflect trade-offs between logistics, data quality, spatial resolution and the disturbance involved in sample extraction. For most common ecological applications we suggest that samples of more than eight Sphagnum stems are likely to be desirable. PMID- 28992523 TI - Two new species of Ripella (Amoebozoa, Vannellida) and unusual intragenomic variability in the SSU rRNA gene of this genus. AB - Two new species, Ripella decalvata and R. tribonemae (Amoebozoa, Vannellida), are described and the diversity of known strains assigned to the genus analyzed. Ripella spp. are closely similar to each other in the light microscopic characters and sequences of small-subunit (SSU) ribosomal RNA gene, but differences in the cell coat structure and cytochrome oxidase (COI) gene sequences are more prominent. SSU rRNA in R. platypodia CCAP1589/2, R. decalvata and R. tribonemae demonstrates an unusual pattern of intragenomic variation. Sequencing of multiple molecular clones of this gene produced numerous sequence variants in a number of specific sites. These sites were usually terminal parts of several variable helices in all studied strains. Analysis of all known Ripella strains shows that SSU rRNA sites differing between strains of different origin are mainly restricted to these areas of the gene. There are only two sites, which differ between strains, but not within genomes. This intragenomic variability of the SSU rRNA gene, seemingly characteristic of all Ripella spp., was never reported to be so extensive in Amoebozoa. The data obtained show another example of complex organization of rRNA gene cluster in protists and emphasize caution needed when interpreting the metagenomic data based on this marker. PMID- 28992524 TI - Early reduction of serum TARC levels may predict for success of ABVD as frontline treatment in patients with Hodgkin Lymphoma. AB - BACKGROUND: Many efforts have been made to predict prognosis of newly diagnosed Hodgkin Lymphoma (HL) patients. Objective of this study was to investigate the association between early reduction of Thymus and Activation-Regulated Chemokine after the first ABVD cycle (TARC-1) and prognosis of HL patients. METHODS: Serum samples of 116 HL patients were collected at baseline, after every ABVD cycle and during follow-up. The 99th centile of TARC distribution in a group of 156 independent healthy subjects (800pg/ml) was considered as cut-off for discriminating between abnormal and normal TARC values. FINDINGS: 101 patients out of 116 had baseline TARC above 800pg/ml (median value 27515pg/ml (IQR, 11001 68139)) and were the object of this analysis. TARC-1 significantly decreased to a median value of 556pg/ml (IQR, 378-977pg/ml). TARC-1 values below 800pg/ml were associated with success of therapy (p=0.0003) and PET-2 negativity (p=0.001). TARC-1<=800pg/ml identified a population with a significantly higher 5-years PFS in the whole cohort (90.1% vs 55.6%; p<0.0001) and in both subgroups of advanced (p=0.003) and early stage patients (p=0.021). At multivariable analysis, TARC-1 was significant independent predictor of PFS (p=0.0035). INTERPRETATION: Early reduction of TARC serum levels can predict success of treatment, being associated with achievement of interim PET-2 negative and favorable long-term outcome in HL patients receiving ABVD as front-line therapy. PMID- 28992525 TI - Have we pushed the needle for treatment of Type 1 diabetes? AB - Studies with immunologics have shown that the natural history of Type 1 diabetes can be modified. These studies have targeted key mediators of the disease and recent analyses, together with studies in preclinical models have identified mechanisms that may be involved in the clinical effects. Several issues remain including specificity of the interventions, adverse effects of the treatments, and duration of their effects. Future studies are likely to include more specific approaches with agents such as cell therapies with selected immune regulatory subsets, antigen specific therapies, and combinations of agents with complementary mechanisms of activity. PMID- 28992526 TI - Improved efficacy with targeted pharmacogenetic-guided treatment of patients with depression and anxiety: A randomized clinical trial demonstrating clinical utility. AB - The objective of this study was to evaluate the effect of pharmacogenetics-guided treatment on patients diagnosed with depression and/or anxiety, in a diverse set of clinical settings, as compared to the standard of care. The trial design followed a prospective, randomized, subject- and rater-blinded approach enrolling 685 patients from clinical providers specializing in Psychiatry, Internal Medicine, Obstetrics & Gynecology, and Family Medicine. The NeuroIDgenetix(r) test uses a genetic variant panel of ten genes, along with concomitant medications, to make medication management recommendations based on gene-drug and drug-drug interactions for over 40 medications used in the treatment of depression and anxiety. Pharmacogenetic testing was performed at the initial screening visit and baseline patient assessments were determined using the 17 item Hamilton Rating Scale for Depression (HAM-D17) and the Hamilton Rating Scale for Anxiety (HAM-A). Following enrollment and randomization, pharmacogenetic results for subjects assigned to the experimental group were provided to physicians to guide treatment selection, while control subjects were treated according to the usual standard of care. HAM-D17 and HAM-A assessments were collected at 4 weeks, 8 weeks, and 12 weeks after baseline to assess the efficacy of therapeutic selection. In patients diagnosed with depression, response rates (p = 0.001; OR: 4.72 [1.93-11.52]) and remission rates (p = 0.02; OR: 3.54 [1.27 9.88]) were significantly higher in the pharmacogenetics-guided group as compared to the control group at 12 weeks. In addition, patients in the experimental group diagnosed with anxiety showed a meaningful improvement in HAM-A scores at both 8 and 12 weeks (p = 0.02 and 0.02, respectively), along with higher response rates (p = 0.04; OR: 1.76 [1.03-2.99]). From these results, we conclude that pharmacogenetic-guided medication selection significantly improves outcomes of patients diagnosed with depression or anxiety, in a variety of healthcare settings. PMID- 28992527 TI - Sex differences in the mediators of functional disability in Major Depressive Disorder. AB - The aim of this study was to investigate sex differences in discrete domains of psychopathology as mediators of functional disability among individuals with Major Depressive Disorder (MDD). Adults (ages 18-65) with moderate-to-severe MDD (n = 100) and age-, sex-, and education-matched healthy controls (HC; n = 100) participated in a clinical trial validating the THINC-integrated tool, a newly developed cognitive assessment tool for patients with MDD. Variables assessed as possible mediators included depression symptom severity, anxiety symptoms, sleep disturbance, perceived cognitive deficits, and objective cognitive performance. Functional disability was assessed using the total score on the Sheehan Disability Scale. Separate mediation analyses were conducted for men and women. No significant differences were detected between men and women on the assessed domains of psychopathology or functional disability (ps > 0.05). However, the mediation analyses demonstrated different patterns with respect to determinants of functional disability in MDD between men and women. Functional disability was mediated by anxiety (95% CI: -3.17, -0.28) and sleep disturbance (95% CI: -0.69, 0.05) among men and by depressive symptom severity (95% CI: -7.82, -0.32) among women. These preliminary results instantiate the need to dimensionalize psychopathology in MDD. Our results at least in part support the hypothesis that, consistent with the sex differences in the prevalence and illness presentation of MDD, determinants of functional outcomes also differ between men and women, underscoring the need to consider sex differences in order to improve functional outcomes in the treatment of MDD. PMID- 28992529 TI - A comprehensive structural model for the human KCNQ1/KCNE1 ion channel. AB - The voltage-gated KCNQ1/KCNE1 potassium ion channel complex, forms the slow delayed rectifier (IKs) current in the heart, which plays an important role in heart signaling. The importance of KCNQ1/KCNE1 channel's function is further implicated by the linkage between loss-of-function and gain-of-function mutations in KCNQ1 or KCNE1, and long QT syndromes, congenital atrial fibrillation, and short QT syndrome. Also, KCNQ1/KCNE1 channels are an off-target for many non cardiovascular drugs, leading to fatal cardiac irregularities. One solution to address and study the mentioned aspects of KCNQ1/KNCE1 channel would be the structural studies using a validated and accurate model. Along the same line in this study, we have used several top-notch modeling approaches to build a structural model for the open state of KCNQ1 protein, which is both accurate and compatible with available experimental data. Next, we included the KCNE1 protein components using data-driven protein-protein docking simulations, encompassing a 4:2 stoichiometry to complete the picture of the channel complex formed by these two proteins. All the protein systems generated through these processes were refined by long Molecular Dynamics simulations. The refined models were analyzed extensively to infer data about the interaction of KCNQ1 channel with its accessory KCNE1 beta subunits. PMID- 28992528 TI - Adjuvant therapy in renal cell carcinoma. AB - Several drugs have demonstrated clinical activity in metastatic renal cell carcinoma (mRCC). The identification of key metabolic pathways has led to the development of novel targeted therapies which have drastically changed the treatment paradigm of mRCC. Moreover, immune-checkpoint inhibitors have recently shown significant activity in advanced disease. Despite these advancements, the role of adjuvant therapy in localized, non-metastatic RCC remains unclear. The utility of many of these agents in the adjuvant setting is currently being actively explored. In this review, we will summarize the main clinical trials investigating adjuvant therapy in renal cell carcinoma, focusing primarily on immunotherapy and targeted agents. PMID- 28992531 TI - Orbitofrontal structural markers of negative affect in alcohol dependence and their associations with heavy relapse-risk at 6 months post-treatment. AB - BACKGROUND: Alcohol relapse is often occurring to regulate negative affect during withdrawal. On the neurobiological level, alcoholism is associated with gray matter (GM) abnormalities in regions that regulate emotional experience such as the orbitofrontal cortex (OFC). However, no study to our knowledge has investigated the neurobiological unpinning of affect in alcoholism at early withdrawal and the associations of OFC volume with long-term relapse risk. METHODS: One hundred and eighty-two participants were included, 95 recently detoxified alcohol dependent patients (ADP) and 87 healthy controls (HC). We measured affective states using the positive and negative affect schedule (PANAS). We collected T1-weighted brain structural images and performed Voxel based morphometry (VBM). RESULTS: Findings revealed GM volume decrease in alcoholics in the prefrontal cortex (including medial OFC), anterior cingulate gyrus, and insula. GM volume in the medial OFC was positively associated with NA in the ADP group. Cox regression analysis predicted that risk to heavy relapse at 6 months increases with decreased GM volume in the medial OFC. CONCLUSIONS: Negative affect during alcohol withdrawal was positively associated with OFC volume. What is more, increased GM volume in the OFC also moderated risk to heavy relapse at 6 months. Reduced GM in the OFC poses as risk to recovery from alcohol dependence and provides valuable insights into transient negative affect states during withdrawal that can trigger relapse. Implications exist for therapeutic interventions signifying the OFC as a neurobiological marker to relapse and could explain the inability of ADP to regulate internal negative affective states. PMID- 28992530 TI - Effects of different antihypertensive medication groups on cognitive function in older patients: A systematic review. AB - BACKGROUND: Chronic hypertension has been associated with an increased risk of cognitive decline. Although a link between hypertension and cognitive decline has been established, there is less evidence supported by systematic reviews. The main aim was to compare different antihypertensive drug groups in relation to their effect on cognition in older patients without established dementia using a systematic review. METHOD: A systematic search in Medline and Embase through to January 2017 was used to identify randomized controlled clinical trials (RCTs) studying the impact of different antihypertensives on cognition in older patients without dementia. Angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACE-Is), beta-blockers (BBs), diuretics, and calcium channel blockers (CCBs) were included in this review. RESULTS: The systematic search identified 358 studies. The full text of 31 RCTs was reviewed and a total of 15 RCTs were included in the review. Most studies reported an improvement in episodic memory in patients treated with ARBs versus placebo or other types of antihypertensive drugs. No study showed an improvement in cognition in patients who received diuretics, BBs, or CCBs. Heterogeneity was high in most trials (predominantly in the blinding of participants and investigators). CONCLUSION: This review suggests that ARBs can improve cognitive functions in the elderly, especially episodic memory. ACE-Is, diuretics, BBs and CCBs did not seem to improve cognitive function in the elderly but were similarly effective in blood pressure lowering as ARBs. PMID- 28992532 TI - Commentary on "Neuropsychological deficits in adults age 60 and above with attention deficit hyperactivity disorder". PMID- 28992533 TI - Neural correlates of affective and non-affective cognition in obsessive compulsive disorder: A meta-analysis of functional imaging studies. AB - Obsessive compulsive disorder (OCD) is characterized by intrusive thoughts and repetitive ritualistic behaviors and has been associated with diverse functional brain abnormalities. We sought to synthesize current evidence from functional magnetic resonance imaging (fMRI) studies and examine their alignment to pathogenetic models of OCD. Following systematic review, we identified 54 task fMRI studies published in the last decade comparing adults with OCD (n=1186) to healthy adults (n=1159) using tasks of affective and non-affective cognition. We used voxel-based quantitative meta-analytic methods to combine primary data on anatomical coordinates of case-control differences, separately for affective and non-affective tasks. We found that functional abnormalities in OCD cluster within cortico-striatal thalamic circuits. Within these circuits, the abnormalities identified showed significant dependence on the affective or non-affective nature of the tasks employed as circuit probes. In studies using affective tasks, patients overactivated regions involved in salience, arousal and habitual responding (anterior cingulate cortex, insula, caudate head and putamen) and underactivated regions implicated in cognitive and behavioral control (medial prefrontal cortex, posterior caudate). In studies using non-affective cognitive tasks, patients overactivated regions involved in self-referential processing (precuneus, posterior cingulate cortex) and underactivated subcortical regions that support goal-directed cognition and motor control (pallidum, ventral anterior thalamus, posterior caudate). The overall pattern suggests that OCD related brain dysfunction involves increased affective and self-referential processing, enhanced habitual responding and blunted cognitive control. PMID- 28992534 TI - The association between metacognitive abilities and outcome measures among people with schizophrenia: A meta-analysis. AB - BACKGROUND: Deficits in metacognition are one of the major causes of the difficulties experienced by individuals with schizophrenia. Studies have linked these deficits to symptom exacerbation and deterioration in psychosocial functioning. The aim of the present meta-analysis was to examine the extensive existing literature regarding metacognitive deficits among persons with schizophrenia; a further aim was to assess the extent to which metacognitive abilities are linked to outcome measures of symptoms and psychosocial functioning. METHOD: We conducted a systematic literature search of studies examining the relationship between metacognitive abilities and outcome measures among people with schizophrenia. We then analyzed the data using a random-effects meta-analytic model with Cohen's d standardized mean effect size. RESULTS: Heterogeneity analyses (k=32, Cohen's d=-.12, 95% CI.-1.92 to 1.7) produced a significant Q-statistic (Q=456.89) and a high amount of heterogeneity, as indicated by the I2 statistic (93.04%), suggesting that moderator analyses were appropriate. As hypothesized, measure type moderated the metacognitive deficit with homogenous effect for psychosocial functioning measures (Q=9.81, I2=19.47%, d=.94. 95% CI .58 to 1.2) and symptoms (Q=19.87, I2=0%, d=-1.07, 95% CI -1.18 to .75). Further analysis found homogenous effects for MAS-A subscales as well as PANSS factors of symptoms. CONCLUSION: Our meta-analysis results illustrated a significant association between metacognitive deficits and both symptomatic and psychosocial functioning measures. These links suggest that the associations between metacognitive abilities and symptomatic outcomes are different from those between metacognitive abilities and psychosocial functioning measures. Intriguing hypotheses are raised regarding the role that metacognitive abilities play in both symptoms and psychosocial functioning measures of people diagnosed with schizophrenia spectrum disorders. PMID- 28992535 TI - Quality of life in schizophrenia and bipolar disorder: The impact of symptomatic remission and resilience. AB - BACKGROUND: Health-related quality of life (HRQOL) is significantly affected in individuals with schizophrenia or bipolar I disorder (BD-I). The current study investigated whether symptomatic remission and resilience might differently impact HRQOL in these patients. METHODS: Fifty-two patients with schizophrenia and 60 patients suffering from BD-I from outpatient mental health services as well as 77 healthy control subjects from the general community were included into a cross-sectional study. HRQOL and resilience were assessed using the WHOQOL-BREF and the Resilience Scale. In patients, psychopathology was quantified by the Positive and Negative Syndrome Scale or the Montgomery Asberg Depression Rating Scale and the Young Mania Rating Scale, respectively. RESULTS: Notably, both patient groups showed lower HRQOL and resilience compared to control subjects, non-remitted patients indicated lower HRQOL than remitted ones. The effect of remission on HRQOL was significantly larger in patients with BD-I than in those with schizophrenia but did not explain the difference in HRQOL between groups. Resilience predicted HRQOL in all three groups. When accounting for the effect of resilience among remitted patients, only the difference in HRQOL between schizophrenia patients and control subjects was significant. CONCLUSION: These findings demonstrate the impact of symptomatic remission and resilience on HRQOL of both patients suffering from schizophrenia and BD-I and indicate that these factors are especially relevant for HRQOL of patients with BD-I. PMID- 28992536 TI - How many receptor-like kinases are required to operate a pollen tube. AB - Successful fertilization depends on active molecular dialogues that the male gametophyte can establish with the pistil and the female gametophyte. Pollen grains and stigmas must recognize each other; pollen tubes need to identify the pistil tissues they will penetrate, follow positional cues to exit the transmitting tract and finally, locate the ovules. These molecular dialogues directly affect pollen tube growth rate and orientation. Receptor-like kinases (RLKs) are natural candidates for the perception and decoding of extracellular signals and their transduction to downstream cytoplasmic interactors. Here, we update knowledge regarding how RLKs are involved in pollen tube growth, cell wall integrity and guidance. In addition, we use public data to build a pollen tube RLK interactome that might help direct experiments to elucidate the function of pollen RLKs and their associated proteins. PMID- 28992537 TI - What is not, but might be: The disnarrated in parents' stories of their child's cancer treatment. AB - The study of illness narratives is based on the premise that stories are told for a reason and storytellers make narrative decisions on what to include and leave out of a story, the style of narration, the place where the story is told and the audience. Through this narrative work, they situate themselves in particular ways and make sense of the illness and the world around them. In this article, we explore the disnarrated, a style of narration that features events that do not happen, but are nonetheless referred to in the story. The aim of the article is to illustrate the additional layers of meaning that can be uncovered from illness stories when attention is paid to what did not happen, but, yet, is still part of the story. We draw from a qualitative study carried out with 17 parents whose children were diagnosed with cancer and were receiving medical care in Argentina. We carried out narrative interviews with the parents and participant-observation in hospital areas and the hotels where they resided during treatment. The analysis of the interview transcripts was carried out using a holistic understanding of the narratives and focusing on the identification of themes that appeared disnarrated. The fieldnotes from the observations were used to contextualize the narrative analysis. The disnarrated, in its many manifestations, produced a layer of analysis of parents' stories of treatment patterned by parents' desires, hopes and fears. The disnarrated was used by parents to discuss alternative care trajectories and express fears regarding what the future would bring for the child and family. The disnarrated is a useful analytical tool for examining illness stories as it points to storytellers' views of what is acceptable or desirable in their world and their hopes and preferences for alternative realities. PMID- 28992539 TI - Cross-lagged associations between posttraumatic stress symptoms and coping self efficacy in long-term recovery: A four-wave comparative study. AB - RATIONALE: Trauma-related coping self-efficacy (CSE) - in brief, the perceived ability to cope with the aftermath of a traumatic event - has been shown to affect psychological outcomes. A previous study showed that CSE affects subsequent PTSS levels, but not vice versa among a sample exposed 0-6 months ago. OBJECTIVE: In this four-wave follow-up study we examined the cross-lagged relationships between CSE and posttraumatic stress symptoms (PTSS) among those exposed to PTEs (potentially traumatic events) 1-2 years before T1 in order to examine direction of influence. Research questions were: 1) what are the cross lagged associations between CSE and PTSS levels among those exposed to PTE in the relatively long-term (1-2 years ago, called PTE long-term group), and 2) to what extent do these associations differ from the cross lagged associations among those exposed to PTE in the relatively short-term (0-6 months ago)? METHOD: Study samples consist of adult respondents of a representative internet panel who experienced a PTE between 1 and 2 years before T1, and did not experience any new PTE between T1 and T3 (long-term group, N = 438) and those exposed in the six months before T1, and not exposed to any additional PTE (short-term group, N = 400). Levels of CSE and PTSS were measured with 4-month intervals. In addition, prospectively assessed personality traits and peritraumatic distress were entered in the analyses. RESULTS: Structural equation modeling showed that CSE perceptions will continue to influence subsequent PTSS levels in the long-term, just as they did in the short-term. Contrary to the more short-term post-exposure period however, CSE levels do not just influence recovery from PTSS. Over time, degree of PTSS experienced also influences subsequent CSE perceptions. CONCLUSION: Results suggest that while trauma-related CSE perceptions are relatively robust in the short-term recovery period, they can be affected by posttraumatic stress in the long-term. PMID- 28992538 TI - Health lifestyles across the transition to adulthood: Implications for health. AB - Research has long established the importance of individual health behaviors such as cigarette smoking for adult morbidity and mortality. However, we know little about how health behaviors cluster into health lifestyles among adolescents and young adults in the United States, or in turn, how such health lifestyles are associated with young adult health outcomes. This study establishes health lifestyles as distinct group phenomena at three developmental time points in a single cohort: late adolescence (ages 15-17), early adulthood (ages 20-24), and young adulthood (ages 26-31). We then identify the associations between these health lifestyles and young adult health outcomes. We use the National Longitudinal Study of Adolescent to Adult Health (Add Health), a nationally representative sample of U.S. adolescents followed into adulthood, and latent class analysis and regression models. We uncover diverse health lifestyles among adolescents, early adults, and young adults; however, few individuals engaged in a consistently salubrious lifestyle at any developmental stage. People with less healthy lifestyles also tended to exhibit poorer health in young adulthood. Our results showed that young adult health lifestyles were significantly associated with young adult cardiovascular risk. Moreover, health lifestyles in each of the three developmental stages were associated with young adult self-rated health, and accounting for lifestyles in later stages explained some of these associations. Overall, this study suggests a portrait of problematic health lifestyles among a nationally representative cohort of young Americans, with associated patterns of relatively poor physical health among those with poor health lifestyles. PMID- 28992540 TI - Kids in space: Measuring children's residential neighborhoods and other destinations using activity space GPS and wearable camera data. AB - INTRODUCTION: Defining the boundary of children's 'neighborhoods' has important implications for understanding the contextual influences on child health. Additionally, insight into activities that occur outside people's neighborhoods may indicate exposures that place-based studies cannot detect. This study aimed to 1) extend current neighborhood research, using data from wearable cameras and GPS devices that were worn over several days in an urban setting; 2) define the boundary of children's neighborhoods by using leisure time activity space data; and 3) determine the destinations visited by children in their leisure time, outside their neighborhoods. METHOD: One hundred and fourteen children (mean age 12y) from Wellington, New Zealand wore wearable cameras and GPS recorders. Residential Euclidean buffers at incremental distances were paired with GPS data (thereby identifying time spent in different places) to explore alternative definitions of neighborhood boundaries. Children's neighborhood boundary was at 500 m. A newly developed software application was used to identify 'destinations' visited outside the neighborhood by specifying space-time parameters. Image data from wearable cameras were used to determine the type of destination. RESULTS: Children spent over half of their leisure time within 500 m of their homes. Children left their neighborhood predominantly to visit school (for leisure purposes), other residential locations (e.g. to visit friends) and food retail outlets (e.g. convenience stores, fast food outlets). Children spent more time at food retail outlets than at structured sport and in outdoor recreation locations combined. CONCLUSION: Person-centered neighborhood definitions may serve to better represent children's everyday experiences and neighborhood exposures than previous methods based on place-based measures. As schools and other residential locations (friends and family) are important destinations outside the neighborhood, such destinations should be taken into account. The combination of image data and activity space GPS data provides a more robust approach to understanding children's neighborhoods and activity spaces. PMID- 28992541 TI - Pastoral power in HIV prevention: Converging rationalities of care in Christian and medical practices in Papua New Guinea. AB - In his conceptualisation of pastoral power, Michel Foucault argues that modern healthcare practices derive a specific power technique from pastors of the early Christian church. As experts in a position of authority, pastors practise the care of others through implicitly guiding them towards thoughts and actions that effect self-care, and towards a predefined realm of acceptable conduct, thus having a regulatory effect. This qualitative study of healthcare workers from two Christian faith-based organisations in Papua New Guinea examines the pastoral rationalities of HIV prevention practices which draw together globally circulated modern medical knowledge and Christian teachings in sexual morality for implicit social regulation. Community-based HIV awareness education, voluntary counselling and testing services, mobile outreach, and economic empowerment programs are standardised by promoting behavioural choice and individual responsibility for health. Through pastoral rationalities of care, healthcare practices become part of the social production of negative differences, and condemn those who become ill due to perceived immorality. This emphasis assumes that all individuals are equal in their ability to make behavioural choices, and downplays social inequality and structural drivers of HIV risk that are outside individual control. Given healthcare workers' recognition of the structural drivers of HIV, yet the lack of language and practical strategies to address these issues, political commitment is needed to enhance structural competency among HIV prevention programs and healthcare workers. PMID- 28992542 TI - De novo transcriptome sequencing of Camellia sasanqua and the analysis of major candidate genes related to floral traits. AB - Camellia sasanqua is one of the most famous horticultural plants in Camellia (Theaceae) due to its aesthetic appeal as landscape plant. Knowledge regarding the genetic basis of flowering time, floral aroma and color in C. sasanqua is limited, but is essential to breed new varieties with desired floral traits. Here, we described the de novo transcriptome of young leaves, flower buds and flowers of C. sasanqua. A total of 60,127 unigenes were functionally annotated based on the sequence similarity. After analysis, we found that two floral integrator genes, SOC1 and AP1, in flowering time pathway showed evidence of gene family expansion. Compared with 1-deoxy-D-xylulose-5-phosphate pathway, some genes in the mevalonate pathway were most highly expressed, suggesting that this might represent the major pathway for terpenoid biosynthesis related to floral aroma in C. sasanqua. In flavonoid biosynthesis pathway, PAL, CHI, DFR and ANS showing significantly higher expression levels in flowers and flower buds might have important role in regulation of floral color. The top five most transcription factors (TFs) families in C. sasanqua transcriptome were MYB, MIKC, C3H, FAR1 and HD-ZIP, many of which have a direct relationship with floral traits. In addition, we also identified 33,540 simple sequence repeats (SSRs) in the C. sasanqua transcriptome. Collectively, the C. sasanqua transcriptome dataset generated from this study along with the SSR markers provide a new resource for the identification of novel regulatory transcripts and will accelerate the genetic improvement of C. sasanqua breeding programs. PMID- 28992543 TI - Seasonal dynamics of photosynthetic activity in the representive brown macroalgae Sagrassum thunbergii (Sargassaceae Phaeophyta). AB - The present study evaluates the seasonal photosynthetic performances of Sargassum thunbergii via chlorophyll fluorescence technique. During summer and early winter, no significant change was observed in maximum photochemical efficiency (Fv/Fm), and performance index (PIabs). During late winter and early spring, Fv/Fm, and PIabs decreased significantly, implying that S. thunbergii photosystem II (PSII) suffered apparent photoinhibition. Subsequently, PSII gradually recovered during late spring and summer, as evidenced by an increase of both parameters. Throughout the year, the maximum decrease in the slope of MR/MR0 maintained low values indicated that photosystem I (PSI) was incative, the initial rate of P700+ re-reduction maintained low value indicated that cyclic electron transport (CET) were inactive; nevertheless, a seasonal down-regulation of both PSI and CET during late winter and early spring could be detected. The weak performance of PSI and CET can potentially limit the flexibility in response to winter stress and result in a delayed recovery of PSII. In conclusion, the seasonal variability of S. thunbergii photosynthetic activity was characterized by three periods: active state, down-regulation and restoration. The rapid growth during early spring was accompanied by weak photosynthetic performance, indicating that the carbohydrates consumed during this period were derived from previously stored starch. PMID- 28992544 TI - The influence of different light quality and benzene on gene expression and benzene degradation of Chlorophytum comosum. AB - Benzene, a carcinogenic compound, has been reported as a major indoor air pollutant. Chlorophytum comosum (C. comosum) was reported to be the highest efficient benzene removal plant among other screened plants. Our previous studies found that plants under light conditions could remove gaseous benzene higher than under dark conditions. Therefore, C. comosum exposure to airborne benzene was studied under different light quality at the same light intensity. C. comosum could remove 500 ppm gaseous benzene with the highest efficiency of 68.77% under Blue:Red = 1:1 LED treatments and the lowest one appeared 57.41% under white fluorescent treatment within 8 days. After benzene was uptaken by C. comosum, benzene was oxidized to be phenol in the plant cells by cytochrome P450 monooxygenase system. Then, phenol was catalyzed to be catechol that was confirmed by the up-regulation of phenol 2-monooxygenase (PMO) gene expression. After that, catechol was changed to cic, cis-muconic acid. Interestingly, cis,cis muconic acid production was found in the plant tissues higher than phenol and catechol. The result confirmed that NADPH-cytochrome P450 reductase (CPR), cytochrome b5 (cyt b5), phenol 2-monooxygenase (PMO) and cytochrome P450 90B1 (CYP90B1) in plant cells were involved in benzene degradation or detoxification. In addition, phenol, catechol, and cis,cis-muconic acid production were found under the Blue-Red LED light conditions higher than under white fluorescent light conditions due to under LED light conditions gave higher NADPH contents. Hence, C. comosum under the Blue-Red LED light conditions had a high potential to remove benzene in a contaminated site. PMID- 28992545 TI - Downregulation of SIRT2 Inhibits Invasion of Hepatocellular Carcinoma by Inhibiting Energy Metabolism. AB - Hepatocellular carcinoma (HCC) is one of the most common neoplasms, and metastasis is the most important feature for HCC-related deaths. Mounting evidence implies the dynamic regulatory role of SIRT2, a histone deacetylase, in cancer cells. Unfortunately, the role of SIRT2 and the antitumor activity of its inhibition are not known in HCC. The present study aims to evaluate the biological function of SIRT2 in HCC and identify the target of SIRT2 as well as evaluate its therapeutic efficacy. We found that SIRT2 was upregulated in HCC tissues compared to adjacent normal tissues, and this was correlated with reduced patient survival. Although CCK8 and colony-formation assays showed that SIRT2 inhibiton marginally promotes proliferation in HCC cell lines, SIRT2 knockdown decreased the invasion of HCC cells. We demonstrated that downregulation of SIRT2 could inhibit its downstream target phosphoenolpyruvate carboxykinase 1 and glutaminase, which is related to mitochondrial metabolism and the E-Cadherin pathway. These results demonstrate, for the first time that downregulation of SIRT2 decreases migration as well as invasion in human HCC cells, indicating that inhibiting SIRT2 may be an effective therapeutic strategy for treating HCC. PMID- 28992546 TI - Differences in posttraumatic stress characteristics by duration of exposure to trauma. AB - Ongoing exposure of civilian populations to war and terror is associated with adverse responses beyond those specified in DSM-5 for PTSD. Current PTSD assessment practices are not fully sensitive to the complex symptomatic picture observed among individuals exposed to ongoing stress and are therefore limited for use in these situations. The current survey aimed to portray the posttraumatic characteristics most salient to ongoing exposure to political conflict. A questionnaire enquiring about various aspects of the posttraumatic consequences of ongoing exposure to political conflict as compared with those associated with a single exposure to trauma was disseminated to therapists throughout the country. Participants were asked to rank 75 posttraumatic characteristics for their relevance to each trauma type (about the symptom frequency and severity) and item mean scores were compared. The sample consisted of 66 responses valid for analysis. Our findings pinpoint some of the posttraumatic characteristics most salient to ongoing exposure to political conflict and highlight the complexity of the posttraumatic picture observed in these situations. Incorporating these in post trauma assessment tools will allow for the development of standardized, reliable definitions, which in turn will allow for more accurate diagnosis and more effective treatment protocols. PMID- 28992547 TI - Medical students' attitudes to mental illnesses and to psychiatry before and after the psychiatric clerkship: Training in a specialty and a general hospital. AB - Medical students' attitudes to mental illnesses and psychiatry may be reshaped during the psychiatric training, with important implications in their future practice of the profession. Therefore, the present study set out to explore the impact of the psychiatric clerkship in students' attitudes, while taking into consideration the site of their practical training. To this end, a total of 678 final-year medical students were recruited. Students completed a self-reported questionnaire entailing the Attitudes to Psychiatry scale, the Attitudes to Mental Illness scale and the Greek Social Distance scale before and after their placement. Findings indicate that the psychiatric clerkship had a positive effect in reducing stigma towards both psychiatry and mental illnesses, with the effect being more pronounced in the general hospital with respect to the former, while in the specialty hospital was more marked regarding the latter. A further exploration of the determinants of change revealed that the improvement discerned in the general hospital was only among those without professional experience of mental illnesses. Therefore, the psychiatric clerkship may exert a substantial influence on shaping favourable attitudes towards mental illnesses and psychiatry; however, other elements should also be taken into consideration, if the clerkship is to tackle stigma in healthcare. PMID- 28992548 TI - The relative contributions of social cognition and self-reflectiveness to clinical insight in enduring schizophrenia. AB - Poor clinical insight represents a major barrier to recovery in schizophrenia. Research suggests that higher-order social cognitive abilities such as theory of mind (TOM) and metacognition contribute to levels of clinical insight. However, few studies have examined whether social cognitive abilities other than TOM are related to clinical insight. Moreover, to date, no investigation has attempted to determine whether the contribution of metacognitive ability to clinical insight can be differentiated from the contribution of higher-order social cognition, despite their conceptual similarity. Therefore, the purpose of this study was to examine the relative contribution of different social cognitive abilities, as well as metacognition, to clinical insight in a large sample of 139 enduring schizophrenia patients, and controlling for established predictors of clinical insight. Hierarchical regression analyses were used to evaluate the portion of variance explained by 3 social cognitive abilities: emotion recognition, TOM, and affective empathy, and the metacognitive ability of self-reflectiveness. Clinical insight levels were assessed using the Schedule for the Assessment of Insight Expanded version. Results indicated that affective empathy and self reflectiveness are the strongest predictors of clinical insight. These results provide insights on the development of targeted interventions for improving clinical insight in this population. PMID- 28992549 TI - How does maternal oxytocin influence children's mental health problem and maternal mental health problem? AB - This study aims to explore the interrelationship among maternal oxytocin (OT) responsiveness, maternal mental health, maternal parenting behavior, and mental health of children under a free-play interaction. 61 mother-child dyads were recruited for the study. Maternal mental health problem and parenting self efficacy were measured using self-reported questionnaires. The mental health problems of children were also evaluated using a mother-reported questionnaire. Furthermore, salivary OT was collected before and after a standardized 10min free play interaction. Parenting behaviors, including eye gaze and touch, were measured during the free-play interaction. Maternal OT responsiveness was significantly associated with less maternal mental health problem, touch frequency, and mental health problem of children but not with parenting self efficacy. In the multivariate linear regression analysis that considers maternal OT responsiveness and maternal and children's mental health problems, maternal OT responsiveness was not associated with the mental health problems of children. This result suggested that maternal mental health problem played a mediational role between maternal OT responsiveness and the mental health problem of children. Results supported the assertion that maternal OT responsiveness contributed to the increased risk of maternal mental health problems and, subsequently, the risk of mental health problems of their children. PMID- 28992550 TI - Gender differences of suicides in children and adolescents: Analysis of 167 suicides in a Mexican population from 2003 to 2013. AB - Suicide is the second cause of death in youth population. The aim of the present study was to analyze demographic characteristics and suicide methods used, as well as to identify gender differences among Mexican children and adolescents (aged 10-17 years) that committed suicide. Between January 2003 and December 2013, 167 suicides of children and adolescents between 10 and 17 years of age were documented by the Secretary of Health of the state of Tabasco, Mexico. All sociodemographic characteristics were compared according to gender. Our sample included 67.7% males and 32.3% females (male to female 2.1:1). The predominant marital status was single (89.6%) and hanging (93.7%) was the principal method of suicide used. Both female and male adolescents were predominantly students (50%); however, female adolescents were more frequently married (17%) and were housewives (26.4%). Our results identified that hanging is the principal suicide method used by children and adolescents in Mexican population; we also detected main gender differences in terms of poisoning/drug toxicity as the method used, occupation and marital status. These results should be taken into consideration when designing suicide prevention programs due to the differences found by gender. PMID- 28992551 TI - Practical capability: The impact of handgun ownership among suicide attempt survivors. AB - Suicide is a leading cause of death and represents a serious public health concern. However, our ability to predict its occurrence has not improved over the last 50 years and we continue to rely on past suicidal behavior as the most robust predictor of future suicidal behavior. Recent theories have emphasized the role of contextual factors that increase capability to act on suicidal thoughts, including access to and familiarity with lethal means. We sought to examine the impact of handgun ownership, a component of practical capability as defined by the Three-Step Theory, on the relationship between past week suicidal ideation and perceived likelihood of making a future suicide attempt within a community sample of previous suicide attempters. Results indicate that, among suicide attempt survivors who are currently suicidal, handgun ownership increases the likelihood of predicting engagement in future suicidal behavior. As self-reported predictions about suicidal behavior have been found to be uniquely predictive of actual suicidal behavior, handgun ownership may facilitate the transition from ideation to action. The relevance of these findings to means safety strategies is discussed. PMID- 28992552 TI - Comparison of clinician-rated and self-report insight in Korean patients with schizophrenia using VAGUS insight scale. AB - This study was aimed to explore self-report auditory verbal hallucinations to provide unique and valuable information in addition to clinician-rated assessment in patients with schizophrenia. The VAGUS (http://www.vagusonline.com) is a recently developed insight scale that includes both clinician-rated (CR) and self report (SR) versions. Insight measures obtained by the two versions of the VAGUS from the clinicians and the patients, respectively, in forty-one patients diagnosed with schizophrenia by DSM-IV-TR criteria were compared. Correlation coefficients for inter-scale convergence and 3-D biplots for multivariate relationship were derived from the subscales of the VAGUS. For external validation, correlation analyses with abridged version of Scale to Assess Unawareness in Mental Disorder (SUMD-A) and PANSS G12 item were conducted. Total scores of VAGUS-CR and -SR were 5.2 +/- 2.6 and 4.9 +/- 2.2, respectively. There was a strong correlation between them along with moderate pairwise correlations among the subscales. The 3-D biplots demonstrated that most subscales were clustered as a single factor apart from self-report Symptom Attribution separated as an independent factor. The VAGUS-CR, not -SR correlated significantly with the SUMD-A and PANSS G12. The utility of the VAGUS in reaching more overall understanding of the elusive phenomenon of insight in patients with schizophrenia is discussed. PMID- 28992553 TI - Validity of instruments for measuring the satisfaction of a woman and her partner with care received during labour and childbirth: Systematic review. AB - BACKGROUND: patient satisfaction as an indicator of quality of care is becoming more and more important. The use of questionnaires is the most common method to evaluate satisfaction with maternity care. Despite the extensive variety of instruments available for this purpose, they vary widely in terms of their content and quality. OBJECTIVES: to identify, assess and summarize the most recent and robust instruments available to measure woman and partner satisfaction with the overall package of care during the labour and birth of their baby within a hospital setting. DESIGN: systematic review. METHODS: sixteen electronic databases were consulted. The research also included hand searching references of identified articles. Studies were assessed by two independent reviewers. Inclusion criteria were that participants were mothers and their respective partners and that the questionnaire was a multidimensional instrument used for measuring satisfaction with care during the labour and birth of a baby. Furthermore, the psychometric properties related to construction, reliability and validity of the questionnaire had to be reported. FINDINGS: seventeen studies were included. The majority of the questionnaires was developed within Europe and was disparate in terms of sample, items, dimensions and collection time. Most of them were limited to healthy women with low obstetric risk pregnancies. Only one instrument included partners as the subject of study. All questionnaires reported at least one aspect of reliability, content and construct validity. CONCLUSIONS: there are a moderate number of instruments capable of measuring maternal satisfaction with the care received during labour and birth within a hospital setting. Our study provides an overview of the most up-to-date, valid and reliable tools available. Further investigations are needed in order to improve existing instruments by performing additional psychometric tests, considering more specific populations and assessing the satisfaction of the partner and mother jointly. IMPLICATIONS FOR PRACTICE: assessments of satisfaction with care during labour and birth are relevant to healthcare professionals, administrators and policy makers. Therefore, these instruments are able to assist them according to their specific needs. PMID- 28992554 TI - Stress in fathers in the perinatal period: A systematic review. AB - BACKGROUND: despite the evidence that fatherhood has a long-term positive and protective effect on men's health, there is also evidence that fatherhood in the perinatal period can be complex and demanding. Due to the potential increase in stressors in the perinatal period, there is reason to hypothesise that it is a time of increased stress for fathers. However, it is not clear how significant a problem stress is for fathers during this stage of life. This is in part, due to the fact that the available research has not been systematically reviewed. PURPOSE: the purpose of this systematic review was to critically appraise the empirical evidence that examined stress in fathers in the perinatal period. DESIGN: systematic review. METHODS: a systematic review protocol was developed and registered with PROSPERO (Reference number: CRD42016035821). The review was guided by the PRISMA reporting process. Electronic databases Medline, CINAHL, the Cochrane Library, PsycARTICLES, PsycINFO, Psychology and Behavioural Sciences Collections were searched to identify studies that met the inclusion criteria. Studies that researched fathers in the perinatal period were included if stress was the principal focus of the research, if stress was in the title and/or aim of the study or if stress was an outcome or dependent variable. Data were extracted and presented in narrative form including tables and figures. FINDINGS: eighteen studies met the inclusion criteria. The findings indicate that fathers experience stress in the perinatal period, particularly at the time of birth. Stress levels were found to increase from the antenatal period to the time of birth, with a decrease in stress levels from the time of birth to the later postnatal period. There are a number of factors that contribute to stress in fathers in the perinatal period and these included negative feelings about the pregnancy, role restrictions related to becoming a father, fear of childbirth and feelings of incompetence related to infant care. The review found that stress has a negative impact on fathers, with higher stress levels contributing to mental health issues such as anxiety, depression, psychological distress and fatigue. KEY CONCLUSION: during the perinatal period fathers experience stress and face unique stressors that can impact negatively on their health and social relationships. PMID- 28992555 TI - The role of multisensory interplay in enabling temporal expectations. AB - Temporal regularities can guide our attention to focus on a particular moment in time and to be especially vigilant just then. Previous research provided evidence for the influence of temporal expectation on perceptual processing in unisensory auditory, visual, and tactile contexts. However, in real life we are often exposed to a complex and continuous stream of multisensory events. Here we tested - in a series of experiments - whether temporal expectations can enhance perception in multisensory contexts and whether this enhancement differs from enhancements in unisensory contexts. Our discrimination paradigm contained near threshold targets (subject-specific 75% discrimination accuracy) embedded in a sequence of distractors. The likelihood of target occurrence (early or late) was manipulated block-wise. Furthermore, we tested whether spatial and modality specific target uncertainty (i.e. predictable vs. unpredictable target position or modality) would affect temporal expectation (TE) measured with perceptual sensitivity (d') and response times (RT). In all our experiments, hidden temporal regularities improved performance for expected multisensory targets. Moreover, multisensory performance was unaffected by spatial and modality-specific uncertainty, whereas unisensory TE effects on d' but not RT were modulated by spatial and modality-specific uncertainty. Additionally, the size of the temporal expectation effect, i.e. the increase in perceptual sensitivity and decrease of RT, scaled linearly with the likelihood of expected targets. Finally, temporal expectation effects were unaffected by varying target position within the stream. Together, our results strongly suggest that participants quickly adapt to novel temporal contexts, that they benefit from multisensory (relative to unisensory) stimulation and that multisensory benefits are maximal if the stimulus-driven uncertainty is highest. We propose that enhanced informational content (i.e. multisensory stimulation) enables the robust extraction of temporal regularities which in turn boost (uni-)sensory representations. PMID- 28992556 TI - Incidence and risk factors of lymphedema after breast cancer treatment: 10 years of follow-up. AB - PURPOSE: To evaluate the incidence and risk factors of lymphedema 10 years after surgical treatment for breast cancer. METHODS: Prospective observational hospital based cohort of women undergoing axillary lymph node dissection. Lymphedema was assessed by indirect volume, measured by circumference, and diagnosed if there was a difference of 200 mL between the arms or if the patient was treated for it. Independent variables were patient, tumour and treatment characteristics. Descriptive statistics were conducted as survival analysis using the Kaplan-Meier estimate. Cox regression was performed, considering a 95% confidence interval (95%CI). RESULTS: The study evaluated 964 women. The cumulative incidence of lymphedema observed was 13.5% at two years of follow-up, 30.2% at five years and 41.1% at 10 years. Final model showed an increased risk for lymphedema among women that underwent radiotherapy (HR = 2.19; 95%CI 1.63-2.94), were obese (HR = 1.52; 95%CI 1.20-1.92), had seroma formation after surgery (HR = 1.46; 95%CI 1.14 1.87), underwent chemotherapy infusion in the affected limb (HR = 1.45; 95%CI 1.12-1.87) or advanced disease staging (HR = 1.41; 95%CI 1.11-1.80). CONCLUSIONS: Cumulative incidence of lymphedema was 41.1%. Women undergoing axillary radiotherapy, obese, who developed seroma, underwent chemotherapy infusion in the affected limb and with advanced disease had a higher risk of lymphedema. PMID- 28992557 TI - Natural and surfactant modified zeolites: A review of their applications for water remediation with a focus on surfactant desorption and toxicity towards microorganisms. AB - The objective of this review is to highlight the need for further investigation of microbial toxicity caused by desorption of surfactant from Surfactant Modified Zeolite (SMZ). SMZ is a low cost, versatile permeable reactive media which has the potential to treat multiple classes of contaminants. With this combination of characteristics, SMZ has significant potential to enhance water and wastewater treatment processes. Surfactant desorption has been identified as a potential issue for the ongoing usability of SMZ. Few studies have investigated the toxicity of surfactants used in zeolite modification towards microorganisms and fewer have drawn linkages between surfactant desorption and surfactant toxicity. This review provides an overview of natural zeolite chemistry, characteristics and practical applications. The chemistry of commonly used surfactants is outlined, along with the kinetics that drive their adsorption to the zeolite surface. Methodologies to characterise this surfactant loading are also described. Applications of SMZ in water remediation are highlighted, giving focus to applications which deal with biological pollutants and where microorganisms play a role in the remediation process. Studies that have identified surfactant desorption from SMZ are outlined. Finally, the toxicity of a commonly used cationic surfactant towards microorganisms is discussed. This review highlights the potential for surfactant to desorb from the zeolite surface and the need for further research into the toxicity of this desorbed surfactant towards microorganisms, including pathogens and environmental microbes. PMID- 28992558 TI - Practical application of direct electron detectors to EBSD mapping in 2D and 3D. AB - The use of a direct electron detector for the simple acquisition of 2D electron backscatter diffraction (EBSD) maps and 3D EBSD datasets with a static sample geometry has been demonstrated in a focused ion beam scanning electron microscope. The small size and flexible connection of the Medipix direct electron detector enabled the mounting of sample and detector on the same stage at the short working distance required for the FIB. Comparison of 3D EBSD datasets acquired by this means and with conventional phosphor based EBSD detectors requiring sample movement showed that the former method with a static sample gave improved slice registration. However, for this sample detector configuration, significant heating by the detector caused sample drift. This drift and ion beam reheating both necessitated the use of fiducial marks to maintain stability during data acquisition. PMID- 28992559 TI - Charging of carbon thin films in scanning and phase-plate transmission electron microscopy. AB - A systematic study on charging of carbon thin films under intense electron-beam irradiation was performed in a transmission electron microscope to identify the underlying physics for the functionality of hole-free phase plates. Thin amorphous carbon films fabricated by different deposition techniques and single layer graphene were studied. Clean thin films at moderate temperatures show small negative charging while thin films kept at an elevated temperature are stable and not prone to beam-generated charging. The charging is attributed to electron stimulated desorption (ESD) of chemisorbed water molecules from the thin-film surfaces and an accompanying change of work function. The ESD interpretation is supported by experimental results obtained by electron-energy loss spectroscopy, hole-free phase plate imaging, secondary electron detection and x-ray photoelectron spectroscopy as well as simulations of the electrostatic potential distribution. The described ESD-based model explains previous experimental findings and is of general interest to any phase-related technique in a transmission electron microscope. PMID- 28992560 TI - Effectiveness and tolerability of Perampanel in children, adolescents and young adults with refractory epilepsy: A UK national multicentre study. AB - PURPOSE: Perampanel is one of the latest antiepileptic drugs (AEDs) approved for the treatment of focal and generalised epilepsy in individuals with epilepsy aged 12 years and older. There is sparse data on the use of Perampanel in children under 12. We conducted a study amongst paediatric neurologists in the United Kingdom to investigate its effectiveness and tolerability as an adjunctive therapy in children of all ages with refractory epilepsy. METHODS: Data was collected via an online questionnaire sent to paediatric neurologists in the UK. Data gathered, prospective in 62 (64.5%) and retrospective in 34 (35.5%) patients, included changes in seizure frequency from baseline and unwanted effects at 3, 6 and 12 months follow-up. Only patients with a minimum follow-up of six months were included. RESULTS: Ninety six patients (48 females) with refractory epilepsy from 11 of 29 tertiary centres were included. Median [IQR] (range) age was 14 years 11 months [12 years, 16 years 6 months] (11 months-24 years 5 months). Seventy three (76%) had focal epilepsy, sixteen (17%) generalised, and seven (7%) patients both generalised and focal epilepsy. The responder rate, >=50% seizure reduction from baseline, was 19% for all seizure types at both 6 and 12 months, 19% and 24% for focal seizures, and 25% and 7% for generalised seizures at these time points respectively. The retention rate was 42% at 12 months. Treatment was discontinued due to unwanted effects in 29 (36.7%) of the 79 patients with follow-up data available up to 12 months: 30% due to challenging behaviour, 14% dizziness, and 7.6% somnolence. CONCLUSION: Perampanel was fairly effective in a heterogeneous group of 96 children and adolescents with very refractory epilepsy. The rate of adverse events leading to discontinuation was considerable in this group. PMID- 28992561 TI - Bridging the gap between the randomised clinical trial world and the real world by combination of population-based registry and electronic health record data: A case study in haemato-oncology. AB - Randomised clinical trials (RCTs) are considered the basis of evidence-based medicine. It is recognised more and more that application of RCT results in daily practice of clinical decision-making is limited because the RCT world does not correspond with the clinical real world. Recent strategies aiming at substitution of RCT databases by improved population-based registries (PBRs) or by improved electronic health record (EHR) systems to provide significant data for clinical science are discussed. A novel approach exemplified by the HemoBase haemato oncology project is presented. In this approach, a PBR is combined with an advanced EHR, providing high-quality data for observational studies and support of best practice development. This PBR + EHR approach opens a perspective on randomised registry trials. PMID- 28992562 TI - A phase IB dose-escalation study of the safety and pharmacokinetics of pictilisib in combination with either paclitaxel and carboplatin (with or without bevacizumab) or pemetrexed and cisplatin (with or without bevacizumab) in patients with advanced non-small cell lung cancer. AB - AIM: The phosphatidylinositol 3-kinase (PI3K) pathway is a potential therapeutic target in non-small cell lung cancer (NSCLC). This study aimed to evaluate the pan-PI3K inhibitor pictilisib in combination with first-line treatment regimens that were the standard of care at the time of study, in patients with NSCLC. PATIENTS AND METHODS: A 3 + 3 dose-escalation study was performed using a starting daily dose of 60 mg pictilisib on days 1-14 of a 21-day cycle. Depending on bevacizumab eligibility and NSCLC histology, patients also received either paclitaxel + carboplatin or pemetrexed + cisplatin, +/- bevacizumab every 3 weeks. The primary objectives of the study were to assess safety and tolerability and to identify dose-limiting toxicities (DLTs), the maximum tolerated dose (MTD) and a recommended phase II dose (RP2D), for each combination. RESULTS: All 66 treated patients experienced at least one adverse event (AE). Grade >=III AEs, serious AEs and deaths occurred in 57 (86.4%), 56 (84.8%) and 9 (13.6%) patients, respectively. Three patients reported DLTs across the four arms of the study. The MTD was not reached in any arm and the RP2D of pictilisib was determined to be 330 mg (capsules) or 340 mg (tablets) on a '14 days on, 7 days off' schedule. The best confirmed response was partial response in 29 (43.9%) patients and stable disease in 20 (30.9%) patients. CONCLUSION: Combining pictilisib with various standard-of-care first-line treatment regimens is feasible from a safety perspective in patients with NSCLC, and encouraging preliminary anti-tumour activity was observed. PMID- 28992564 TI - Evaluation of synthetic aluminum silicate modified by magnesia for the removal of 137Cs, 60Co and 152+154Eu from low-level radioactive waste. AB - The present study concerns the preparation, characterization and testing of an inorganic ion exchanger Aluminum Silicate Modified Magnesia (ASMM). The ASMM composite was prepared using sol-gel technique and characterized by XRD, XRF, FTIR, TGA, DTA, SEM and surface area analysis. The capability of the prepared composite for the removal of (Cs+, Co2+ and Eu3+) from aqueous solution was evaluated. Sorption studies were carried out taking into account important parameters such as (pH, initial concentration, contact time and temperature). Kinetic and isotherm models were applied to the prepared composite, kinetic data is well fitted with pseudo-second order kinetic model, Dubinin-Radushkevich isotherm model indicates that sorption was controlled by chemisorption process. The removal efficiency found to be 80% for Cs+, 90% for Co2+ and 95% for Eu3+. PMID- 28992565 TI - Modeling and experimental data of zirconium-89 production yield. AB - The radionuclide zirconium-89 can be employed for the positron emission tomography (PET). In this study 89Zr excitation function via 89Y(p,n)89Zr reaction was calculated by the TALYS-1.8 code based on microscopic level density model. The formation of 89Zr was simulated using the Monte Carlo simulation code MCNPX to calculate the integral yield in the 89Y target body for threshold up to 40MeV incident-proton energy. The target thickness was based on calculation of the stopping power using the SRIM-2013 code matched to any incident-proton energy. The production yield of the 89Zr simulated with the Monte Carlo method for the 89Y(p,n)89Zr, 89Y(d,2n)89Zr, natSr(alpha,xn)89Zr and natZr(p,pxn)89Zr reactions and the results were in good agreement with published experimental results for the optimum energy range. An experimental yield of 53.1MB/uA for the 15MeV proton-induced on Y2O3 powder as a disk-target obtained for 1h irradiation at the AMIRS cyclotron. PMID- 28992563 TI - Potential role of polymorphisms in the transporter genes ENT1 and MATE1/OCT2 in predicting TAS-102 efficacy and toxicity in patients with refractory metastatic colorectal cancer. AB - BACKGROUND: Trifluridine (FTD) is an active cytotoxic component of the metastatic colorectal cancer (mCRC) drug TAS-102, and thymidine phosphorylase inhibitor (TPI) inhibits the rapid degradation of FTD. We tested whether single nucleotide polymorphisms (SNPs) in genes involved in FTD metabolism and TPI excretion could predict outcome in patients with mCRC treated with TAS-102. PATIENTS AND METHODS: We investigated three different cohorts: a training cohort (n = 52) and a testing cohort (n = 129) both receiving TAS-102 and a control cohort (n = 52) receiving regorafenib. SNPs of TK1, ENT1, CNT1, MATE1, MATE2 and OCT2 were analysed by polymerase chain reaction-based direct DNA sequencing. RESULTS: In the training cohort, patients with any ENT1 rs760370 G allele had a significantly longer progression-free survival (PFS; 3.5 versus 2.1 months, respectively, hazard ratio [HR] 0.44, P = 0.004) and overall survival (OS; 8.7 versus 5.3 months, respectively, HR 0.27, P = 0.003) than the A/A genotype. These findings were validated in the testing cohort (P = 0.021 and 0.009 for PFS and OS, respectively). In addition, the combination of ENT1 rs760370, MATE1 rs2289669 and OCT2 rs316019 SNPs significantly stratified patients with the risk of PFS and OS in both cohorts (P < 0.001 for PFS and OS in the training cohort; P = 0.053 and 0.025 for PFS and OS, respectively, in the testing cohort). No significant differences were observed in the control group. CONCLUSIONS: The combination of ENT1, MATE1 and OCT2 SNPs may serve as a predictive and prognostic marker in mCRC patients treated with TAS-102. PMID- 28992566 TI - Quantification of xanthine- and uric acid-related compounds in urine using a "dilute-and-shoot" technique coupling ultra-high-performance liquid chromatography and high-resolution Orbitrap mass spectrometry. AB - Quantitative analysis of relevant metabolites in biofluids such as urine is often a tedious procedure, since it usually requires extraction, purification or preconcentration. For instance, in the analysis of methylxanthines in urine, a solid-phase extraction is often required. In the current work, a rapid and highly sensitive "dilute-and-shoot" method combining ultra-high-performance liquid chromatography and high-resolution mass spectrometry (UHPLC/HRMS) was validated for urinary determination of twelve analytes: uric acid, hypoxanthine, xanthine, 1-methyluric acid, 1,3-dimethyluric acid, 1-methylxanthine, 3-methylxanthine, 7 methylxanthine, theophylline, theobromine, paraxanthine and caffeine. These analytes are the major physiological metabolites of caffeine, theobromine or theophylline, or final products of purine catabolism. The separation was carried out on a core-shell Kinetek EVO C18 column coupled to a Q Exactive Orbitrap high resolution mass spectrometer equipped with a heated electrospray ionization (HESI) probe, that operated both in positive and negative ionization modes. The twelve analytes eluted from between 1.5 and 10.5min. The lower limit of quantification (LLOQ) values ranged from 0.25 to 2.5ng/mL, and the calibration curves were linear from the LLOQ to 100ng/mL. The only pretreatment needed was to dilute each urine sample (typically to 1/500) with 0.1% formic acid solution, and then filter the diluted sample before injecting it into the UHPLC system. With this high dilution, there were no significant matrix effects, and the intra- and inter-day precision and accuracy values were acceptable (coefficients of variance and relative errors below 15%, except for the LLOQ, for which they were below 20%). Furthermore, the analysis of spiked urine samples with 25ng/mL of the target analytes showed excellent recoveries and precision levels for the twelve analytes. To our knowledge, there is no other published method that allows for the simultaneous determination of the concentrations of these twelve compounds, nor has a previously reported method been indicated to show such low LLOQ values as we have for the majority of the analytes. We expect our protocol to be useful for nutritional assessments, interventional studies, kidney stone research, and purine metabolism studies. PMID- 28992567 TI - Conditional survival of pediatric, adolescent, and young adult soft tissue sarcoma and bone tumor patients. AB - BACKGROUND: Survival estimates for soft tissue sarcomas (STS) and malignant bone tumors (BT) diagnosed in pediatric, adolescent, and young adult patients are not easily available. We present survival estimates based on a patient having survived a defined period of time (conditional survival). Conditional survival estimates for the short-term were calculated for patients from diagnosis to the first five years after diagnosis and for patients surviving in the long-term (up to 20 years after diagnosis). METHODS: We identified 703 patients who were diagnosed with a STS or BT at age <=25 years from January 1, 1986 to December 31, 2012 at a large pediatric oncology center in Salt Lake City, Utah, United States. We obtained cancer type, age at diagnosis, primary site, and demographic data from medical records, and vital status through the National Death Index. Cancer stage was available for a subset of the cohort through the Utah Cancer Registry. Cox proportional hazards models, adjusted for age and sex, calculated survival estimates for all analyses. RESULTS: Short-term survival improves over time for both sarcomas. Short-term survival for STS from diagnosis (Year 0) did not differ by sex, but short-term survival starting from 1-year post diagnosis was significantly worse for male patients (Survival probability 1-year post-diagnosis [SP1]:77% [95% CI:71-83]) than female patients (SP1:86% [81-92]). Survival for patients who were diagnosed at age <=10 years (Survival probability at diagnosis [SP0]:85% [79-91]) compared to diagnosis at ages 16-25 years (SP0:67% [59-75]) was significantly better at all time-points from diagnosis to 5-years post diagnosis. Survival for axial sites (SP0:69% [63-75]) compared to extremities (SP0:84% [79-90]) was significantly worse from diagnosis to 1-year post diagnosis. Survival for axial BT (SP0: 64% [54-74] was significantly worse than BT in the extremities (SP0:73% [68-79]) from diagnosis to 3-years post diagnosis. Relapsed patients of both sarcoma types had significantly worse short-term survival than non-relapsed patients. Long-term survival for STS in this cohort is 65% at diagnosis, and improves to 86% 5-years post-diagnosis. BT survival improves from 51% at diagnosis to 78% at 5-years post-diagnosis. CONCLUSION: Conditional survival for short- and long-term STS and BT improve as time from diagnosis increases. Short-term survival was significantly affected by patients' sex, age at diagnosis, cancer site, and relapse status. PMID- 28992568 TI - Self-rated health and associated factors in elderly patients with non-Hodgkin lymphoma. AB - BACKGROUND: Self-rated health is a useful indicator for understanding health issues in elderly populations and considered to be a predictor of adverse health outcomes in this group. This study aims to identify factors associated with self rated health in elderly people with non-Hodgkin's lymphoma. METHODS: Cross sectional study performed at a cancer referral hospital in Rio de Janeiro, Brazil, included 162 patients, aged 60 or more years. All patients received a Multidimensional Geriatric Assessment, including seven health dimensions, and socio-demographic, epidemiological and it were collected clinical data. Descriptive analyses were performed and prevalence ratios were calculated to assess associations between self-rated health and the independent variables. Multivariate analysis was performed using Poisson's regression, to a <=0.05 level of statistical significance. RESULTS: The study population mean age was 68.8 (SD=7.1) years; most were women, lived with a partner and had little education. Prevalence of fair/poor self-rated health was 33.6%. Being female, not living with a partner, functional dependence, depressive symptoms and nutritional risk/malnutrion showed associations with fair/poor self-rated health. In the multiple model, dependence in instrumental activities of daily living (PR 2.96; 95%CI 1.66-5.30) and presence of depressive symptoms (PR 1.78; 95%CI 1.15-2.75) remained associated with fair/poor health. CONCLUSION: Variation in perceived health status supports the hypothesis that self-rated health is related to multiple issues, regardless of disease status. The risk profile for poor self rated health identified may be a useful tool in care for older cancer patients, as it points to those at higher risk of adverse health outcomes. PMID- 28992569 TI - 4-Alkyliden-azetidinones modified with plant derived polyphenols: Antibacterial and antioxidant properties. AB - Antimicrobial resistance is one of the major and growing concerns in hospital- and community acquired infections, and new antimicrobial agents are therefore urgently required. It was reported that oxidative stress could contribute to the selection of resistant bacterial strains, since reactive oxygen species (ROS) revealed to be an essential driving force. In the present work 4-alkylidene azetidinones, a new class of antibacterial agents, were functionalized with phytochemical polyphenolic acids such as protocatechuic, piperonyl, caffeic, ferulic, or sinapic acids and investigated as dual target antibacterial antioxidant compounds. The best candidates showed good activities against multidrug resistant clinical isolates of MRSA (MICs 2-8 MUg/mL). Among the new compounds, two revealed the best antioxidant capacity with TEAC-DPPH and TEAC ABTS being significantly more active than Trolox(r). PMID- 28992570 TI - The use of new chemically modified cellulose for heavy metal ion adsorption. AB - We have developed a simple one-step method to synthesize novel supramolecular polysaccharide composite from cellulose (CEL) and dibenzo-18-crown 6 using ceric ammonium nitrate as initiator. The [CEL+DB18C6] composites obtained retain properties of their components, namely superior mechanical strength (from CEL), excellent adsorption capability for heavy metal ions from DB18C6. More importantly, the [CEL+DB18C6] composites exhibit truly supramolecular properties. By itself CEL and DB18C6 can adsorb heavy metals. However, adsorption capability of the composite was substantially and synergistically enhanced by adding DB18C6 to CEL. That is, the removal percentage value for Cd2+, Zn2+, Ni2+, Pb2+ and Cu2+ by [CEL+DB18C6] composites are much higher than removal percentage values of individual CEL and DB18C6 composites. It seems that DB18C6 synergistically interact with CEL to form more stable complexes with heavy metals, and as a consequence, the [CEL+DB18C6] composite can adsorb relatively larger amount heavy metals. The adsorption parameters, such as pH, adsorbent dose, contact time, initial metal ion concentration and temperature were optimized. Desorption studies revealed that the regeneration of modified cellulose saturated with these metallic ions depends on the type and concentration of the regenerating solution (NH4Cl, HNO3, NaCl and CaCl2). PMID- 28992571 TI - Rhamnolipid stabilized nano-chlorapatite: Synthesis and enhancement effect on Pb and Cd-immobilization in polluted sediment. AB - Phosphate (P) compounds are usually used as chemical amendment for in situ remediation of heavy metal polluted sediment. However, the low deliverability, weak utilization and potential risk of eutrophication inhibit the application of most P materials. Therefore, rhamnolipid (Rha), a kind of anionic biosurfactant which has algicidal activity, was employed in this study to synthesize a new kind of nano-chlorapatite (nClAP) for Pb and Cd immobilization. Characterization results showed that the Rha stablized nClAP (Rha-nClAP) was uniformly distributed in suspensions within about 5nm. Experimental data demonstrated that the combination of Rha and nClAP could greatly enhance the Pb- and Cd-immobilization efficiencies, promoting their transformation from labile fractions to stable fractions through precipitation or adsorption processes, especially when the Rha approached to its critical micelle concentration. And Rha-nClAP could also decrease both the TCLP-leachable Pb and Cd with maximum reduction efficiencies of 98.12% and 96.24%, respectively, which also presented concentration dependence of Rha. Changes of available phosphorus implied the dissolution of nClAP during the treatment and the detection of organic matter demonstrated that the microorganisms may involve in the remediation. PMID- 28992572 TI - Ecotoxicity of the insensitive munitions compound 3-nitro-1,2,4-triazol-5-one (NTO) and its reduced metabolite 3-amino-1,2,4-triazol-5-one (ATO). AB - The insensitive munitions compound 3-nitro-1,2,4-triazol-5-one (NTO) was recently approved by the U.S. Army to replace cyclotrimethylene trinitramine (RDX) in conventional explosives. As its use becomes widespread, concern about the potential toxicity of NTO increases. NTO can undergo microbial reduction to 3 amino-1,2,4-triazol-5-one (ATO), which is recalcitrant in waterlogged soils. In this study, the acute toxicity of NTO and ATO towards various organisms, including microorganisms (i.e., methanogenic archaea, aerobic heterotrophs, and Aliivibrio fischeri (Microtox assay)), the microcrustacean Daphnia magna (ATO only), and zebrafish embryos (Danio rerio), was assessed. NTO was notably more inhibitory to methanogens than ATO (IC50=1.2mM,>62.8mM, respectively). NTO and ATO did not cause noteworthy inhibition on aerobic heterotrophs even at the highest concentrations tested (32.0mM). High concentrations of both NTO and ATO were required to inhibit A. fischeri (IC20=19.2, 22.4mM, respectively). D. magna was sensitive to ATO (LC50=0.27mM). Exposure of zebrafish embryos to NTO or ATO (750MUM) did not cause lethal or developmental effects (22 endpoints tested). However, both compounds led to swimming behavior abnormalities at low concentrations (7.5MUM). The results indicate that the reductive biotransformation of NTO could enhance or lower its toxicity according to the target organism. PMID- 28992573 TI - Rethinking indicators of problematic cannabis use in the era of medical cannabis legalization. AB - INTRODUCTION: Recent rapid changes in medical cannabis policies and increases in medical use of cannabis have raised new research questions related to potential effects of medical cannabis legalization on cannabis use problems. In order to investigate such effects there is a need for screening tools that are sensitive to the fact that people may be using for medical and/or recreational purposes. This article critically assesses whether screening tools designed to measure cannabis use problems in recreational users are meaningful as measures of problems resulting from medical use. RESULTS AND CONCLUSIONS: It is possible that existing cannabis problem screening tools are not equally valid across medical and recreational users, since individual screening items have different implications for recreational and medical users. For instance, items that measure use that deviates from common patterns of recreational use (use before midday and use alone) reflect normative assumptions that non-problematic recreational use will occur in contexts of parties or social gatherings. However, use before midday and alone are how people typically take medication for chronic medical health problems. There is thus a need to develop and validate criteria for problematic use in medical cannabis patients. PMID- 28992574 TI - Emerging role for the medial prefrontal cortex in alcohol-seeking behaviors. AB - The medial prefrontal cortex (mPFC) plays an important role in high-order executive processes and sends highly organized projections to sub-cortical regions controlling mood, motivation and impulsivity. Recent preclinical and clinical studies have demonstrated alcohol-induced effects on the activity and composition of the PFC which are implicated in associative learning processes and may disrupt executive control over impulsivity, leading to an inability to self limit alcohol intake. Animal studies have begun to dissect the role of the mPFC circuitry in alcohol-seeking behavior and withdrawal, and have identified a key role for projections to sub-cortical sites including the extended amygdala and the nucleus accumbens (NAc). Importantly, these studies have highlighted that alcohol can have contrasting effects on the mPFC compared to other addictive substances and also produce differential effects on the structure and activity of the mPFC following short-term versus long-term consumption. Because of these differences, how the mPFC influences the initial aspects of alcohol-seeking behavior and how we can better understand the long-term effects of alcohol use on the activity and connectivity of the mPFC need to be considered. Given the lack of preclinical data from long-term drinking models, an increased focus should be directed towards identifying how long-term alcohol use changes the mPFC, in order to provide new insights into the mechanisms underlying the transition to dependence. PMID- 28992575 TI - Organizational downsizing and alcohol use: A national study of U.S. workers during the Great Recession. AB - Organizational downsizing, which represents the reduction of an organization's workforce, results in a stressful work environment for those who survive the downsizing. However, we know little about the association between surviving an organizational downsizing and employee alcohol use. This study explored the association between exposure to organizational downsizing and four dimensions of alcohol use during the Great Recession. Also explored were the moderating influences of length of recession exposure, state drinking culture, gender, age, education, family income, and financial demands. Data for this study came from a national telephone survey of U.S. workers that was conducted from December 2008 to April 2011 (N=2296). The results revealed that exposure to organizational downsizing was positively associated with usual frequency of drinking, number of drinks consumed per usual drinking occasion, and both the frequency of binge drinking and drinking to intoxication. Length of exposure to the recession moderated the association between organizational downsizing exposure and usual number of drinks consumed. The conditional effects revealed that this association became stronger as length of exposure to the recession increased. Furthermore, age moderated the associations between organizational downsizing exposure and the usual number of drinks consumed and the frequency of binge drinking and intoxication. The conditional effects revealed that these associations were positive and significant among young survivors (ages 40 or younger), but were nonsignificant among middle-aged survivors (over 40years of age). State drinking culture, gender, education, family income, and financial demands did not moderate the associations between organizational downsizing exposure and alcohol use. PMID- 28992576 TI - When the party continues: Impulsivity and the effect of employment on young adults' post-college alcohol use. AB - BACKGROUND: The transition from college to work is both an exciting and potentially high risk time for young adults. As students transition from academic settings to full-time employment, they must navigate new social demands, work demands, and adjust their drinking behaviors accordingly. Research has shown that there are both protective factors and risk factors associated with starting a new job when it comes to alcohol use, and individual differences can moderate these factors. METHOD: 1361 students were recruited from 4 geographically diverse universities and followed 1month pre- and 1month post-graduation. Drinking frequency, quantity, consequences, and impulsivity were assessed. RESULTS: Full time employment was related to increased drinking quantity but not related to changes in other drinking outcomes. However, impulsivity moderated the relationship between employment and drinking. For those reporting higher levels of impulsivity at baseline, full-time employment was associated with an increase in drinking variables (quantity and frequency), whereas drinking was unaffected by full-time employment status among those reporting lower levels of impulsivity. Implications for future research are discussed. PMID- 28992577 TI - Smoking and drinking behaviors of military spouses: Findings from the Millennium Cohort Family Study. AB - INTRODUCTION: The associations between stressful military experiences and tobacco use and alcohol misuse among Service members are well documented. However, little is known about whether stressful military experiences are associated with tobacco use and alcohol misuse among military spouses. METHODS: Using 9872 Service member spouse dyads enrolled in the Millennium Cohort Family Study, we employed logistic regression to estimate the odds of self-reported cigarette smoking, risky drinking, and problem drinking among spouses by Service member deployment status, communication regarding deployment, and stress associated with military-related experiences, while adjusting for demographic, mental health, military experiences, and Service member military characteristics. RESULTS: Current cigarette smoking, risky drinking, and problem drinking were reported by 17.2%, 36.3%, and 7.3% of military spouses, respectively. Current deployment was not found to be associated with spousal smoking or drinking behaviors. Communication about deployment experiences with spouses was associated with lower odds of smoking, but not with risky or problem drinking. Spouses bothered by communicated deployment experiences and those who reported feeling very stressed by a combat related deployment or duty assignment had consistently higher odds of both risky and problem drinking. CONCLUSIONS: Our findings suggest that contextual characteristics about the deployment experience, as well as the perceived stress of those experiences, may be more impactful than the simple fact of Service member deployment itself. These results suggest that considering the impact of deployment experiences on military spouses reveals important dimensions of military community adaptation and risk. PMID- 28992578 TI - Testing weight motives and guilt/shame as mediators of the relationship between alcohol use and physical activity. AB - OBJECTIVES: Test whether weight motives and guilt/shame mediate the positive relationship between physical activity and alcohol use among college-attending young adults. DESIGN: A longitudinal design was employed. METHOD: Young adults who were attending college (N=371) completed two self-administered questionnaires separated by approximately one month. Heavy episodic drinking was assessed at Time 1. Vigorous physical activity, moderate physical activity, weight motives, and guilt/shame were assessed at Time 2. RESULTS: Results are consistent with weight motives as a mediator of the positive relationship between heavy episodic drinking and vigorous physical activity. Results were inconsistent with guilt/shame as a mediator of this relationship. There was no statistically significant relationship between heavy episodic drinking and moderate physical activity. CONCLUSIONS: Heavy episodic drinking was related to vigorous but not to moderate physical activity in the subsequent 30-days. Furthermore, the results are consistent with weight motives as a mediator of the relationship between alcohol use and vigorous physical activity. PMID- 28992579 TI - E-cigarette use among treatment-seeking smokers: Moderation of abstinence by use frequency. AB - INTRODUCTION: Emerging literature suggests that frequency of use of electronic cigarettes (e-cigarettes) may be an important moderating variable in the relationship between e-cigarette use and smoking cessation. However, few studies have focused specifically on treatment-seekers, a group that may differ in important ways from smokers in the general population. This study looks at the relationship between e-cigarette use frequency and abstinence among a sample of treatment-seeking tobacco users. METHODS: Seven-month follow-up survey data from N=2760 treatment-seeking tobacco users who utilized statewide tobacco quitlines in three states were used to assess the relationship between 30-day point prevalence abstinence and e-cigarette use frequency at follow-up. E-cigarette use was examined in two ways. First, we looked at any use in the past 30days versus no use. Additionally, past 30-day e-cigarette use frequency was categorized into four groups: 0days, 1-5days - infrequent, 6-29days - intermediate, 30days - daily. Logistic regression models were constructed predicting 30-day point prevalence tobacco abstinence. RESULTS: Both infrequent (AOR=0.35; CI=0.20-0.59) and intermediate (AOR=0.50; CI=0.32-0.80) past 30-day e-cigarette use were associated with lower rates of tobacco abstinence versus no past 30-day use. However, daily e-cigarette users (AOR=1.16; CI=0.71-1.70) had similar 30-day abstinence when compared to non-users. CONCLUSIONS: Results from this study of treatment-seekers support findings from studies of general population tobacco users that suggest frequency of e-cigarette use is an important moderating variable in the relationship between e-cigarette use and tobacco cessation. Future studies should employ more refined measures of e-cigarette use. PMID- 28992580 TI - Efficacy and outcomes of a mobile app targeting alcohol use in young people. AB - Mobile apps provide a highly accessible way of reducing alcohol use in young people. This paper determines the 1-month efficacy and 2, 3 and 6month outcomes of the Ray's Night Out app, which aims to increase alcohol knowledge and reduce alcohol use in young people. User-experience design and agile development processes, informed by the Information-Motivation-Behavioral skills model and evidence-based motivational interviewing treatment approaches guided app development. A randomized controlled trial comparing immediate versus 1-month delayed access to the app was conducted in 197 young people (16 to 25years) who drank alcohol in the previous month. Participants were assessed at baseline, 1, 2, 3 and 6months. Alcohol knowledge, alcohol use and related harms and the severity of problematic drinking were assessed. App quality was evaluated after 1 month of app use. Participants in the immediate access group achieved a significantly greater increase in alcohol knowledge than the delayed access group at 1-month, but no differences in alcohol use or related problems were found. Both groups achieved significant reductions in the typical number of drinks on a drinking occasion over time. A reduction in maximum drinks consumed was also found at 1month. These reductions were most likely to occur in males and problem drinkers. Reductions in alcohol-related harm were also found. The app received a high mean quality (M=3.82/5, SD=0.51). The Ray app provides a youth-friendly and easily-accessible way of increasing young people's alcohol knowledge but further testing is required to determine its impact on alcohol use and related problems. PMID- 28992582 TI - Fat or fiction? Effects of body size, eating pathology, and sex upon the body schema of an undergraduate population. AB - Although there is a growing consensus that women with anorexia nervosa have a distorted body schema, the origins of this disturbance remain uncertain. The present investigation examined the effects of body size, eating pathology, and sex upon the body schema of an at-risk, undergraduate population. In Study 1, 98 participants mentally simulated their passage through apertures. When aperture width was manipulated, narrow and broad women over- and under-estimated their spatial requirements for passage, respectively. This relationship was exacerbated by dietary restraint. When aperture height was manipulated, short and tall men over- and under-estimated their spatial requirements for passage, respectively. Study 2 (N=32) replicated the association between women's veridical and internally-represented widths, although no significant effects of eating pathology were observed. Our findings suggest that body schema enlargement is not necessarily pathological, and may be driven by normal perceptual biases and internalised sociocultural body ideals. PMID- 28992581 TI - Simultaneous alcohol & tobacco use expectancies in young adult co-users. PMID- 28992583 TI - Autonomic dysfunction of gastric motility in major depression. AB - BACKGROUND: Patients suffering from major depressive disorder (MDD) often complain about somatic symptoms. Cardiac complaints have been examined predominantly. However, gastrointestinal complaints are also reported frequently and are associated with worse outcomes. The research concerning changes in gastric motility of these patients is rather sparse. The aim of our study was to determine dysfunction of gastric motility and gastrointestinal symptoms in MDD. The duration and severity of MDD were examined regarding its influence over gastric emptying. METHODS: Gastric emptying was determined by a 13C-acetate breath test in patients with MDD (n = 29) and healthy control subjects (n = 51). Prior to this, depressive illness was operationalized using external and self assessment scales (HAMD-21, MADRS, BDI, CGI). Whether the severity or duration of MDD influenced the gastric emptying parameters was examined using Spearman's correlation. In addition, autonomic complaints were recorded by means of an ANS score. Each ANS score item was determined using a Mann-Whitney U or Kruskal Wallis test concerning the gastric emptying parameters. RESULTS: There was a significant difference in the parameters of the maximum gastric emptying rate (Tmax) and gastric half emptying time T1/2b between patients with MDD and healthy control subjects (Tmax 66.21min vs 53.35min, p < 0.006, T1/2b 207.59min vs 133.27min, p < 0.005). There was a significant negative correlation between Tmax and the severity of MDD determined with the depression rating scales BDI (Spearman's rank - 0.521, p = 0.013) and HAMD-21 (r - 0.384, p = 0.048). No correlation was found between the duration of MDD and the maximum gastric emptying rate (r - 0.125, p = 0.519) and gastric half emptying time (r - 0.62, p = 0.749). CONCLUSION: Gastrointestinal motility is significantly impaired in patients with MDD compared to healthy control subjects. Autonomic complaints were indicated frequently in MDD patients. The duration of MDD had no influence over the time of gastric emptying. There was a significant negative correlation between the severity of MDD and Tmax, indicating that the Tmax was reached earlier with the progression of MDD. The slowing of gastric motility in MDD patients is likely a result of a dysfunction of the autonomic nervous system. PMID- 28992585 TI - Video game play and anxiety during late adolescence: The moderating effects of gender and social context. AB - BACKGROUND: Few studies have examined factors that moderate the relationship between playing video games and adolescent psychological adjustment. Therefore, the primary goal of this study was to examine the relationship between playing video games and anxiety symptomatology in a sample of 441 11th and 12th grade students, while considering both gender and the social context (whether they played alone or with others). METHODS: Participants (66% non-Hispanic White) were administered a survey (including measures of technology use and anxiety symptomatology) in school at baseline and one year later. RESULTS: Both gender and the social context moderated the relationship between playing video games and anxiety symptomatology. Boys who played video games the most had the lowest levels of anxiety, whereas girls who played video games the most had the highest levels of anxiety. This relationship was exacerbated in the context of playing with others. LIMITATIONS: Although the study has a number of strengths including the longitudinal design and the diverse sample, the study relied on self-report data. In addition, the sample was limited to adolescents residing in the Mid Atlantic United States. Therefore, caution should be taken in regard to generalizing the results. CONCLUSIONS: Findings from this study underscore the need to consider both gender and the social context when examining the relationship between playing video games and adolescent psychological adjustment. PMID- 28992584 TI - OGT-related mitochondrial motility is associated with sex differences and exercise effects in depression induced by prenatal exposure to glucocorticoids. AB - BACKGROUND: Prenatal exposure to glucocorticoids (GCs) has been found to trigger abnormal behaviors and deleterious neurological effects on offspring both in animals and in humans. The sex differences in depression have been replicated in numerous studies across cultures, persisting throughout the reproductive years. As an X-linked gene in rodents and in humans, O-GlcNAc transferase (OGT) may provide a novel perspective for the sex differences in depression. METHODS: In the last third of pregnancy (gestational day 14-21), rats were subcutaneously administered either 0.13mg/kg dexamethasone-21-phosphate disodium salt (0.1mg/kg DEX) or vehicle (0.9% saline) once a day for 7 days. Adolescent (4 weeks) offspring were then trained in a swimming program or not. RESULTS: Here we found that adult offspring rats exposed to DEX prenatally exhibited sex-specific depression-like behaviors, males being more vulnerable than females. Swimming exercise ameliorated the above-mentioned depressive syndromes, which may be a compensatory effect for male disadvantage suffering from prenatal stress. Furthermore, the effects of prenatal DEX exposure and swimming exercise on depression were associated with OGT-related mitochondrial motility, including PINK1/Parkin pathway and AKT/GSK3beta pathway. LIMITATIONS: Representative kymographs of mitochondrial motility were not detected and no causal effects were obtained by OGT gene overexpression or gene knockout in this study. CONCLUSIONS: Our results provide a new perspective for better understanding sex differences and exercise effects in depression and may offer new mechanism-based therapeutic targets for depression. PMID- 28992586 TI - Self-compassion is more effective than acceptance and reappraisal in decreasing depressed mood in currently and formerly depressed individuals. AB - BACKGROUND: Self-compassion has recently been discussed as an effective affect regulation strategy for reducing negative affective states. The primary aim of the current study was to compare the efficacy of self-compassion to the more established strategies of acceptance and reappraisal. METHODS: For this purpose, we induced depressed mood in formerly, currently and never depressed individuals (n=30 each) at four different time-points. Participants were instructed to regulate their emotions after each mood induction by either waiting, employing self-compassion, accepting their emotions or reappraising the situation. Level of depressed mood was assessed before and after each mood induction and regulation phase. RESULTS: Across groups, decreases in depressed mood were greater in the self-compassion compared to the waiting and acceptance conditions. In recovered and never depressed participants, self-compassion was also more effective than reappraisal. LIMITATIONS: Our results rely solely on self-report data. CONCLUSIONS: Our finding that self-compassion is superior to acceptance and equally or more effective than reappraisal encourages future research on how self compassion interventions can be used to enhance the efficacy and stability of current depression treatments. PMID- 28992587 TI - Aberrant resting-state cerebellar blood flow in major depression. AB - BACKGROUND: Abnormal cortical cerebral blood flow and gray matter volume have been frequently reported in patients with major depressive disorder (MDD). In contrast, although the role of the cerebellum in MDD pathophysiology has attracted considerable interest more recently, studies investigating both functional and structural aspects of cerebellar integrity are scarce. METHODS: In this study, we used structural and functional magnetic resonance imaging (MRI) to investigate cerebellar volume and regional cerebellar blood flow (rCBF) at rest in clinically acute MDD patients (n = 22) and healthy controls (n = 18). We acquired high-resolution structural images at 3 T together with perfusion images obtained with continuous arterial spin labeling. Cerebellar structure and function were investigated using cerebellum-optimized analysis techniques. RESULTS: Markedly increased rCBF was found in bilateral cerebellar areas VIIa and VIIIb (p < 0.05 family-wise-error [FWE] corrected). Significant differences in cerebellar volume between patients and controls were not found (p < 0.05, FWE corrected). Left cerebellar area VIIa perfusion was significantly associated with depressive symptoms, as measured by the Hamilton Depression Rating Scale. LIMITATIONS: Potential limitations of this study include the modest sample size, the cross-sectional design, the lack of task-related imaging and the heterogeneity of drug treatment. CONCLUSIONS: The data suggest contributions of "affective" cerebellar regions to MDD pathophysiology and symptom expression. While cerebellar perfusion at rest is compromised in MDD, cerebellar volume seems to be less affected. PMID- 28992588 TI - Comments on "Predictive factors for the outcome of high flow nasal cannula therapy in a pediatric intensive care unit: Is the SpO2/FiO2 ratio useful?" PMID- 28992589 TI - Epigallocatechin-3-gallate promotes healthy lifespan through mitohormesis during early-to-mid adulthood in Caenorhabditis elegans. AB - The green tea polyphenol epigallocatechin-3-gallate (EGCG) is widely consumed as a dietary supplement. Its potential properties include slowing aging and extending lifespan, although how exactly this is achieved remains unclear. Here, we report that EGCG promoted healthy lifespan in Caenorhabditis elegans when administered throughout or only at early-to-mid adulthood. Specifically, EGCG extended lifespan in an inverted U-shaped dose-response manner. The life extending mechanism was stimulated by EGCG-induced production of reactive oxygen species (ROS). Additionally, EGCG triggered mitochondrial biogenesis to restore mitochondrial function. The EGCG-induced increase in lifespan depends on known energy sensors such as AMPK/AAK-2, as well as SIRT1/SIR-2.1 and FOXO/DAF-16. Interestingly, aging decreased the response to EGCG and progressively neutralized its beneficial effects on longevity. Collectively, our findings link EGCG to the process of mitohormesis and suggest an inducible, AMPK/SIRT1/FOXO-dependent redox signaling module that could be invoked in different contexts to extend healthy lifespan. Its effectiveness is higher in younger adults and declines with age. PMID- 28992590 TI - La3+/La(OH)3 loaded magnetic cationic hydrogel composites for phosphate removal: Effect of lanthanum species and mechanistic study. AB - In this study, La3+(ion)/La(OH)3-W/La(OH)3-EW-loaded magnetic cationic hydrogel (MCH) composites were fabricated in situ and characterized to investigate the effects of lanthanum species on phosphate adsorption. The corresponding maximum P adsorption capacities of MCH-loaded La3+(ion) (MCH-La3+(ion)), La(OH)3-W (MCH La(OH)3-W), and La(OH)3-EW (MCH-La(OH)3-EW) were 70.5 +/- 2.67, 69.2 +/- 3.5, and 90.2 +/- 2.9 mg P/g, respectively. Furthermore, for MCH-La(OH)3-EW, the P adsorption capacity was maintained relatively stable and high at pH 4.5-11 because of the ligand exchange, electrostatic interactions, and Lewis acid-base interactions. The enhanced adsorption of P was achieved over a wide pH range, as well as in the presence of competing anions (including Cl-, NO3-, SO42-, HCO3- and SiO44-). Moreover, the exhausted MCH-La(OH)3-EW could be easily regenerated by a NaOH-NaCl desorption agent with above 72% adsorption capacity remained during five recycles. The column adsorption capacity of MCH-La(OH)3-EW reached ~3500 bed volumes (BV) (~67.7 mg P/g) as the concentration of P decreased from 5 mg/L to 0.1 mg/L. The ATR-IR, Raman, and XPS deconvolution results revealed that both MCH and lanthanum compounds, including La3+(ion), La(OH)3-W and La(OH)3-EW, contributed to the phosphate adsorption because of the electrostatic interactions between -N+(CH3)3 and phosphate, as well as the formation of LaPO4.xH2O. PMID- 28992591 TI - Nutrient loading impacts on culturable E. coli and other heterotrophic bacteria fate in simulated stream mesocosms. AB - Understanding fecal indicator bacteria persistence in aquatic environments is important when making management decisions to improve instream water quality. Routinely, bacteria fate and transport models that rely on published kinetic decay constants are used to inform such decision making but may not adequately represent instream conditions. The objective of this work was to evaluate bacterial responses to applied nutrient amendments and provide additional information regarding bacterial response to applied changes that can be incorporated into future modeling efforts. Re-created stream mesocosms were established in laboratory-based, repurposed algae raceways filled with water and sediment from a small, 3rd order Southeast Texas stream. Mesocosm treatments consisted of low (10x) or high (50x) nutrient doses above ambient water concentrations operated at low (0.032 m/s) or high (0.141 m/s) flow rates. Escherichia coli and heterotrophic bacterial concentrations were quantified in water and sediment over 22 days. No significant differences in kinetic constants were observed among E. coli in water or sediment, and only E. coli in sediment showed any growth response. Heterotrophic plate counts revealed a pronounced growth response in water and sediment within 24 h of nutrient addition but did not differ significantly from control mesocosms. Significant kinetic constant differences between E. coli and heterotrophic bacteria in water were identified (p < 0.01) but did not differ significantly in sediment (p > 0.48). Results indicate that nutrient addition does affect microbial numbers instream, but competition from heterotrophic bacteria may prevent an E. coli growth response. PMID- 28992592 TI - Inactivation of microbiota from urban wastewater by single and sequential electrocoagulation and electro-Fenton treatments. AB - This work aims at comparing the ability of two kinds of electrochemical technologies, namely electrocoagulation (EC) and electro-Fenton (EF), to disinfect primary and secondary effluents from municipal wastewater treatment plants. Heterotrophic bacteria, Escherichia coli, enterococci, Clostridium perfringens spores, somatic coliphages and eukaryotes (amoebae, flagellates, ciliates and metazoa) were tested as indicator microorganisms. EC with an Fe/Fe cell at 200 A m-2 and natural pH allowed >5 log unit removal of E. coli and final concentration below 1 bacteria mL-1 of coliphages and eukaryotes from both effluents in ca. 60 min, whereas heterotrophic bacteria, enterococci and spores were more resistant. A larger removal was obtained for the primary effluent, probably because the flocs remove higher amount of total organic carbon (TOC), entrapping more easily the microbiota. EF with a boron-doped diamond (BDD) anode and an air-diffusion cathode that produces H2O2 on site was first performed at pH 3.0, with large or even total inactivation of microorganisms within 30 min. A more effective microorganism removal was attained as compared to EC thanks to *OH formed from Fenton's reaction. A quicker disinfection was observed for the secondary effluent owing to its lower TOC content, allowing the attack of greater quantities of electrogenerated oxidants on microorganisms. Wastewater disinfection by EF was also feasible at natural pH (~7), showing similar abatement of active microorganisms as a result of the synergistic action of generated oxidants like active chlorine and coagulation with iron hydroxides. A sequential EC/EF treatment (30 min each) was more effective for a combined decontamination and disinfection of urban wastewater. PMID- 28992593 TI - Small, mobile, persistent: Trifluoroacetate in the water cycle - Overlooked sources, pathways, and consequences for drinking water supply. AB - Elevated concentrations of trifluoroacetate (TFA) of more than 100 MUg/L in a major German river led to the occurrence of more than 20 MUg/L TFA in bank filtration based tap waters. Several spatially resolved monitoring programs were conducted and discharges from an industrial company were identified as the point source of TFA contamination. Treatment options for TFA removal were investigated at full-scale waterworks and in laboratory batch tests. Commonly applied techniques like ozonation or granulated activated carbon filtration are inappropriate for TFA removal, whereas TFA was partly removed by ion exchange and completely retained by reverse osmosis. Further investigations identified wastewater treatment plants (WWTPs) as additional TFA dischargers into the aquatic environment. TFA was neither removed by biological wastewater treatment, nor by a retention soil filter used for the treatment of combined sewer overflows. WWTP influents can even bear a TFA formation potential, when appropriate CF3-containing precursors are present. Biological degradation and ozonation batch experiments with chemicals of different classes (flurtamone, fluopyram, tembotrione, flufenacet, fluoxetine, sitagliptine and 4:2 fluorotelomer sulfonate) proved that there are yet overlooked sources and pathways of TFA, which need to be addressed in the future. PMID- 28992594 TI - Electrochemistry and electron paramagnetic resonance spectroscopy of cytochrome c and its heme-disrupted analogs. AB - Cytochrome c (cyt c) is one of the most studied conjugated proteins due to its electron-transfer properties and ability to regulate the processes involved in homeostasis or apoptosis. Here we report an electrochemical strategy for investigating the electroactivity of cyt c and its analogs with a disrupted heme moiety, i.e. apocytochrome c (acyt c) and porphyrin cytochrome c (pcyt c). The electrochemical data are supplemented with low-temperature and spin-probe electron paramagnetic resonance (EPR) spectroscopy. The main contribution of this report is a complex evaluation of cyt c reduction and oxidation at the level of surface-localized amino acid residues and the heme moiety in a single electrochemical scan. The electrochemical pattern of cyt c is substantially different to both analogs acyt c and pcyt c, which could be applicable in further studies on the redox properties and structural stability of cytochromes and other hemeproteins. PMID- 28992595 TI - Electrical current generation in microbial electrolysis cells by hyperthermophilic archaea Ferroglobus placidus and Geoglobus ahangari. AB - Few microorganisms have been examined for current generation under thermophilic (40-65 degrees C) or hyperthermophilic temperatures (>=80 degrees C) in microbial electrochemical systems. Two iron-reducing archaea from the family Archaeoglobaceae, Ferroglobus placidus and Geoglobus ahangari, showed electro active behavior leading to current generation at hyperthermophilic temperatures in single-chamber microbial electrolysis cells (MECs). A current density (j) of 0.68+/-0.11A/m2 was attained in F. placidus MECs at 85 degrees C, and 0.57+/ 0.10A/m2 in G. ahangari MECs at 80 degrees C, with an applied voltage of 0.7V. Cyclic voltammetry (CV) showed that both strains produced a sigmoidal catalytic wave, with a mid-point potential of -0.39V (vs. Ag/AgCl) for F. placidus and 0.37V for G. ahangari. The comparison of CVs using spent medium and turnover CVs, coupled with the detection of peaks at the same potentials in both turnover and non-turnover conditions, suggested that mediators were not used for electron transfer and that both archaea produced current through direct contact with the electrode. These two archaeal species, and other hyperthermophilic exoelectrogens, have the potential to broaden the applications of microbial electrochemical technologies for producing biofuels and other bioelectrochemical products under extreme environmental conditions. PMID- 28992596 TI - Deciphering the electric code of Geobacter sulfurreducens in cocultures with Pseudomonas aeruginosa via SWATH-MS proteomics. AB - Interspecies electron transfer (IET) occurs in many microbial communities, enabling extracellular electron exchange for syntrophic utilization of mixed resources. Various mechanisms of IET have been characterized including direct IET (DIET) and hydrogen IET (HIT) but their evolution throughout syntrophic adaptation has not been investigated through an omics approach. A syntrophic coculture of Geobacter sulfurreducens and Pseudomonas aeruginosa was established and evolved in restricted medium. The medium required cooperative metabolism due to preferential utilization of formate and fumarate by P. aeruginosa and G. sulfurreducens respectively. Pure cultures did not yield significant growth while substantial growth was observed in cocultures. The syntrophy was not reliant on phenazine, since Deltaphz mutant strain cocultures grew, however appeared to rely on cytochromes as evidenced from the stunted growth G. sulfurreducens DeltaomcZ and DeltaomcS mutant cocultures. SWATH (sequential window acquisition of all theoretical spectra) MS (mass spectrometry) proteomic analysis of initial cocultures revealed upregulation in DIET-associated cytochromes, whereas adapted cocultures revealed upregulation in HybA, a G. sulfurreducens uptake hydrogenase critical to HIT. This suggests DIET plays a critical role in the establishment of syntrophy between G. sulfurreducens and P. aeruginosa but is later consolidated with HIT as the cocultures adapt. This is the first instance to show a temporal distribution of DIET and HIT within the same coculture. PMID- 28992597 TI - Phytoplankton growth and PSII efficiency sensitivity to a glyphosate-based herbicide (Factor 540(r)). AB - The use of glyphosate-based herbicides in agriculture has increased steadily since the mid 90's and there is now evidence of glyphosate leaching and contamination of aquatic ecosystems. The aim of this study was to evaluate the effects of a glyphosate-based herbicide (Factor 540(r)) on growth and photosynthetic capacity of algae and cyanobacteria. Six algal and three cyanobacterial species/strains, of three different taxonomic groups, were exposed to five glyphosate concentrations (10, 50, 100, 500 and 1000MUgl-1) during 48h. All species have significant growth inhibition at concentrations varying between 50 and 500MUgl-1. The photosynthetic response, after glyphosate exposure, varied among species, but a general pattern has emerged. There was an increase in the amount of photons absorbed (ABS/RC), in dissipated (DIO/RC) and trapped (TRO/RC) energy in the photosystem II reaction centers, along with a decreased of the maximum photosystem II quantum yield (FV/FM) and electron transport per reaction center (ETO/RC). The EC50 and LOEC values for growth and photosynthesis were calculated and established that growth was the most affected parameter by glyphosate-based herbicide, while parameter TRO/RC was the least affected. All species showed reduced growth at glyphosate concentrations lower than the Canadian standard for the protection of aquatic life, set at 800MUgl-1 or the American aquatic life benchmark for acute toxicity in non vascular plants of 12 100MUgl-1 questioning the validity of these thresholds in assessing the risks related to the presence of glyphosate and glyphosate-based herbicides in aquatic systems. PMID- 28992598 TI - Global transcriptomic analysis of zebrafish in response to embryonic exposure to three antidepressants, amitriptyline, fluoxetine and mianserin. AB - Antidepressants are among the most commonly detected pharmaceuticals in aqueous systems, and, as emerging organic pollutants, may exert negative effects on non target aquatic organisms. Previously, it has been revealed that antidepressant exposure significantly inhibits the growth and development of fish during their early developmental stages. Thus, in the present study, we aimed to identify and compare the underlying mechanisms of action of different antidepressants at the transcriptional level using zebrafish (Danio rerio) embryos. Through high throughput RNA sequencing (RNA-Seq) data analysis, 32, 34, and 130 differentially expressed genes (DEGs) were obtained from zebrafish larvae after 120h of embryonic exposure to sublethal concentrations of amitriptyline, fluoxetine, and mianserin, respectively. The expression profiles of the identified DEGs showed similar trends in response to the three antidepressant treatments, suggesting consistent toxic effects of low concentrations of these three drugs on the regulation of gene expression in fish. Several metabolic and signaling pathways, including glycolysis/gluconeogenesis and the insulin pathway, were affected in the exposed fish larvae. The expression profiles of selected DEGs were then verified by the qRT-PCR method, which indicated significant positive correlations with the RNA-Seq results. Next, we determined the concentration-dependent expression patterns of 6 selected DEGs in fish larvae exposed to three antidepressants at a series of environmentally relevant concentrations. The results revealed a significant concentration-dependent reduction in the levels of dual-specificity phosphatase 5 (dusp5) mRNA, as well as a non-concentration dependent gene expression inhibition of prostaglandin D2 synthase b (ptgdsb); the circadian rhythm-related genes, i.e. those encoding nuclear receptor subfamily 1, group D, member 1 (nr1d1) and period 2 (per2); and genes encoding early growth response factors (egr1 and egr4), in the antidepressant-treated fish larvae. In summary, to our knowledge, our findings demonstrate, for the first time, that the three different categories of antidepressants have common effects on the gene expression involved in multiple biological processes and signaling pathways during the early development of fish and thus provide information for characterizing the adverse outcome pathways and on the ecological risk assessment of these pharmaceutical pollutants in the aquatic environment. PMID- 28992599 TI - The effect of restorative materials on cytokines in gingival crevicular fluid. AB - OBJECTIVE: Composition of the restorative materials may cause inflammatory responses by monocyte activation and changes in the levels of cytokine released from different cells. Interleukin-6 (IL-6), interleukin-8 (IL-8) and Tumor necrosis factor alpha (TNF-alpha) are important cytokine for evaluating of the inflammatory process. The aim of this study was to evaluate the different restorative materials used in class V cavities effect on gingival crevicular fluid inflammatory cytokine levels. DESIGN: 60 individuals having Class V carious cavities participated in the study. Cavities were restored with FiltekZ250, DyractXP, Fuji IX, Cavex avalloy restorative materials. Changes in clinical and biochemical parameters were evaluated before restorations, seven and 21days after restorations. Contralateral tooth intact enamel surface was determined as control side. Periotron8000 device was used for detection of GCF volume. Cytokine level of GCF was evaluated by Human ELISA kits. Data were analyzed using Mann-Whitney U test and Wilcoxon signed ranks test. The correlations between clinical parameters and biochemical parameters were examined by Spearman's rank correlation analysis. RESULTS: After restorative treatments PI and GI scores were decreased compared with baseline evaluations. There was a significant difference in GCF levels between experimental and control sites in all groups. GCF IL-6 levels in all groups except Filtek Z250, GCF IL-8 levels in all groups except Fuji IX, GCF TNF alpha level in only Fuji IX showed significant differences between experimental and control sites. CONCLUSIONS: The obtained data supported that all of the tested materials caused changes in GCF cytokine levels. PMID- 28992600 TI - Association of tongue brushing with the number of fungiform taste buds and taste perception: A preliminary study using confocal laser scanning microscopy in combination with a filter-paper disc method. AB - OBJECTIVE: The aim of this study was to investigate the association of tongue brushing with the number of fungiform taste buds and taste perception using a confocal laser scanning microscopy in combination with a filter-paper disc method (FPDM). METHODS: Twenty-four subjects with or without a habit of tongue brushing (11 males and 13 females, 20-46 years old) participated in this study. Nine of the 24 subjects had no habit of tongue brushing (Group 1, n=9). Fifteen subjects had a habit of tongue brushing, and the brushing regions of the tongue were as follows: central region (Group 2, n=7), or entire region (Group 3, n=8) of the tongue dorsum. Using confocal laser scanning microscopy, the average number of taste buds per fungiform papilla (FP) was counted. Taste perception was evaluated using an FPDM. These observations were performed in the midlateral region of the tongue since the distribution of fungiform papillae is large in the midlateral region compared to that in the central region. RESULTS: The subjects in Group 3 showed a significantly decreased number of fungiform taste buds compared to Group 1 and Group 2. Group 3 also showed significantly higher FPDM scores than the other two groups. CONCLUSIONS: Excessive tongue brushing of the entire tongue dorsum, including the midlateral region, may have an association with the decreased number of FP and taste buds and decreased taste sensation. To avoid these conditions, instituting proper tongue brushing methods, such as limiting it to the central region of the tongue and using a light touch, is suggested and is important for the subjects who are eager to participate in tongue brushing. PMID- 28992601 TI - Tooth damage in captive orcas (Orcinus orca). AB - OBJECTIVES: Tooth damage as a result of oral stereotypies is evident in captive orca, yet little research on the topic exists. This study examines the associations between dental pathology, sex, facility, duration of captivity and other factors in captive orca. DESIGN: We evaluated mandibular and maxillary teeth from dental images of 29 captive orca owned by a US-based theme park. Each tooth was scored for coronal wear, wear at or below gum line and bore holes. Fractured and missing teeth were also noted. Summary statistics described the distribution and severity of pathologies; inferential statistics examined how pathologies differed between sexes, between wild-captured and captive-born orcas and between captive orca at four facilities. We also evaluated how dental pathology and duration of captivity were related. RESULTS: Approximately 24% of whales exhibited "major" to "extreme" mandibular coronal tooth wear, with coronal wear and wear at or below gum line highly correlated. More than 60% of mandibular teeth 2 and 3 exhibited fractures. Bore holes were observed primarily among anterior mandibular teeth, with more than 61% of teeth 2 and 3 bearing evidence of having been drilled. Four of five orca with the highest age-adjusted tooth pathology indices were captive-born. CONCLUSIONS: Various dental pathologies were observed across all whales, with pathologies beginning at a young age. Oral stereotypies exhibited by captive orca contributed to the observed dental damage. By making dental and health records of captive whales publicly available, the theme park industry is uniquely positioned to provide further insight into dental pathology and resultant health consequences in captive orca. PMID- 28992602 TI - The viscoelastic response of electrospun poly(vinyl alcohol) mats. AB - Native biological tissues are viscoelastic materials that undergo time-dependent loading in vivo. It is therefore crucial to ensure that biomedical materials have a suitable viscoelastic response for a given application. In this study, the viscoelastic properties of electrospun poly(vinyl alcohol) are investigated using tensile load relaxation testing. A five-parameter generalised Maxwell constitutive model is found to characterise the experimental response. The effect of polymer concentration and electrospinning voltage on model parameters is investigated in detail. The stiffness coefficients for the relaxation process appear to be dependent on the electrospinning conditions used whereas the time constants remain relatively unchanged. It is also observed that the stiffness parameters are linearly correlated with the equilibrium modulus, indicating that a single underlying material property dictates the relaxation moduli. Lastly, it is found that the viscoelastic model parameters are not predicted by the fibre diameter. These results provide an important understanding in designing electrospun mats with desired time-dependent properties. PMID- 28992603 TI - Sex steroid hormones and sex hormone binding globulin levels, CYP17 MSP AI ( 34T:C) and CYP19 codon 39 (Trp:Arg) variants in children with developmental stuttering. AB - Developmental stuttering is known to be a sexually dimorphic and male-biased speech motor control disorder. In the present case-control study, we investigated the relationship between developmental stuttering and steroid hormones. Serum levels of testosterone, dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), oestradiol, progesterone, cortisol, and sex hormone binding globulin (SHBG), as well as the 2nd/4th digit ratio (2D:4D), an indicator of prenatal testosterone level, were compared between children who stutter (CWS) and children who do not stutter (CWNS). Moreover, two SNPs (CYP17 -34 T:C (MSP AI) and CYP19 T:C (Trp:Arg)) of cytochrome P450, which is involved in steroid metabolism pathways, were analysed between the groups. Our results showed significantly higher levels of testosterone, DHT, and oestradiol in CWS in comparison with CWNS. The severity of stuttering was positively correlated with the serum levels of testosterone, DHEA, and cortisol, whereas no association was seen between the stuttering and digit ratio, progesterone, or SHBG. The CYP17CC genotype was significantly associated with the disorder. PMID- 28992604 TI - Photodynamic effects on Fonsecaea monophora conidia and RAW264.7 in vitro. AB - Chromoblastomycosis (CBM), one of the neglected tropical diseases, is hard to cure and easy to be recurrent. Many studies suggest that macrophage is involved in the pathogenesis of chromoblastomycosis and the fungicidal effect of 5 Aminolaevulinic Acid-Based Photodynamic Therapy (ALA-PDT) against F. monophora (one of the main causative agent of chromoblastomycosis) has shown great promise. However, the fungicidal ability of ALA-PDT to F. monophora is still controversial and the molecular mechanism and immune mechanism of ALA-PDT against F. monophora remains poorly documented. In the present work, ALA (5-Aminolaevulinic Acid) was employed as photosensitizer and a LED device was served as light source to investigate photodynamic effect on F. monophora conidia under different ALA-PDT conditions in a direct way. RAW264.7 was stimulated by conidia treated with ALA PDT to study the photodynamic effect on F. monophora conidia in an indirect way. It was observed that ALA-PDT can inactivate F. monophora conidia directly in a concentration-dependent and dose-dependent manner. RAW264.7 was activated indirectly by photodynamically treated conidia. ALA-PDT can enhance the fungicidal ability of RAW264.7 and protect it from Infection-induced apoptosis in an indirect way. ROS generated by photodynamic treated conidia is associated with mitochondrial-related apoptosis in RAW264.7.The results of this investigation demonstrated that ALA-PDT inactivate F. monophora through two way: directly killing F. monophora conidia through ROS-dependent Oxidative damage; activating RAW264.7 in an indirect way. PMID- 28992605 TI - Prospective, multicenter, randomized clinical study to evaluate the clinical efficacy and tolerability of long term mixed ultraviolet and visible light phototherapy in eosinophil nasal polyps. PMID- 28992606 TI - Apoptotic mechanism behind the testicular atrophy in photorefractory and scotosensitive quail: Involvement of GnIH induced p-53 dependent Bax-Caspase-3 mediated pathway. AB - In most of the avian species, daylength or photoperiod is the main environmental factor regulating reproduction. During their annual gonadal cycle, birds once sensitive to short or long day effect develop refractoriness to the same daylength and gonad develop or regress accordingly. The present study investigated the effects of photoperiodic alterations on apoptosis mediated testicular responses of photosensitive/photorefractory and scotosensitive/scotorefractory quail, Coturnix coturnix japonica. Testicular apoptosis in the quail of different photoperiodic conditions was assessed by monitoring the alterations in the local testicular expression of GnRH-I, GnIH, pro-apoptotic proteins (p53 and Bax), inactive caspase (pro-Caspase-3), executioner active-Caspase-3 and inactive/uncleaved PARP-1 (DNA repair enzyme) and TUNEL analysis. Alterations in these parameters indicate that testicular quiescence/regression in scotosensitive and photorefractory quail is mediated by apoptosis of testicular cells and hence apoptosis appears to be the key mechanism of testicular regression in Japanese quail. Present findings demonstrated the underlying molecular mechanism of how avian testes respond differentially to same photoperiodic conditions and exhibit scoto-/photo-sensitivity and refractoriness. It is concluded that photoperiod induced testicular stimulation in photosensitive/scotorefractory quail may be due to apoptotic inhibition and testicular regression in scotosensitive/photorefractory quail is guided by apoptosis, an effect invariably regulated by local action of GnRH and GnIH. PMID- 28992607 TI - Effect of UV radiation and its implications on carotenoid pathway in Bixa orellana L. AB - The current study was undertaken to analyse the effect of short-term UV-B and UV C radiations in provoking carotenoid biosynthesis in Bixa orellana. Seeds of B. orellana were germinated and exposed to the short term UV pre-treatment under controlled environmental condition for 5days. The UV treated young seedlings response in pigment contents; antioxidant enzyme activity and mRNA gene expression level were analysed. The pigment content such as chlorophyll was increased in both UV-B and UV-C treated seedlings, but the total carotenoid level was decreased when compared to the control seedlings this can be attributed to the plant adaptability to survive in a stressed condition. The beta-carotene level was increased in UV-B, and UV-C treated young seedlings. No significant changes have occurred in the secondary pigment such as bixin and ABA. The activity of the antioxidant enzymes such as catalase, peroxidase, and superoxide dismutase was significantly increased in UV-B treated seedlings when compared to the UV-C treated seedlings and control. The mRNA expression of the genes involved in bixin biosynthesis pathways such as DXS, PSY, PDS, LCY-beta, LCY-epsilon, CMT, LCD, ADH and CCD genes showed different expression pattern in UV-B and UV-C treated young seedlings. Further we analysed the gene co-expression network to identify the genes which are mainly involved in carotenoid/bixin biosynthesis pathway. Form our findings the CCD, LCY, PDS, ZDS and PSY showed a close interaction. The result of our study shows that the short term UV-B and UV-C radiations induce pigment content, antioxidant enzyme activity and different gene expression pattern allowing the plant to survive in the oxidative stress condition. PMID- 28992608 TI - Where are we with transformational therapies for patients with cystic fibrosis? AB - The disease cystic fibrosis (CF) is caused by a disturbance in the synthesis or function of the CFTR anion channel. Several types of small molecules geared to overcome the underlying defect in specific patient groups are in the clinical pipeline. Two drugs have obtained regulatory approval. The potentiator ivacaftor brings major clinical benefit in patients with CFTR protein expression at the cell membrane; the combination ivacaftor plus corrector lumacaftor brings a modest benefit for patients homozygous for the most common mutation F508del. The busy drug pipeline puts pressure on the finite CF patient population. Improving CFTR function in patients has at times yielded unexpected findings. The initial success with ivacaftor has set high expectations, has pushed drug prices sky high and has resulted in inequity in drug access. PMID- 28992609 TI - Type D personality in patients with upper extremity musculoskeletal illness: Internal consistency, structural validity and relationship to pain interference. AB - OBJECTIVE: Type D personality - the joint tendency toward negative affectivity (NA) and social inhibition (SI) - is associated with greater symptom perception and negative health outcomes among various patient populations. We investigated Type D personality among patients with upper extremity musculoskeletal illness. METHOD: In cross-sectional design, we estimated the prevalence of Type D personality in this population and explored the associations of two different Type D conceptualizations (i.e., categorical and dimensional as the NA*SI interaction) and the individual NA and SI traits with pain interference as well as structural-internal validity of DS14. RESULTS: The categorical Type D personality and greater NA and SI were associated with pain interference above and beyond descriptive variables, but the interaction term between NA and SI was not. NA explained a larger proportion of the variance in pain interference than SI. DS14 showed a two-factor structure and high internal consistency in this sample. CONCLUSIONS: The categorical Type D allows for identifying individuals who struggle with recovery from musculoskeletal injury. Although the dimensional conceptualization didn't prove to be associated with pain interference, NA and SI appear to have individual effects on pain interference, with most variance being accounted for by NA. Implications for clinical care are discussed. PMID- 28992610 TI - A fully automated microfluidic-based electrochemical sensor for real-time bacteria detection. AB - A fully automated microfluidic-based electrochemical biosensor was designed and manufactured for pathogen detection. The quantification of Escherichia coli was investigated with standard and nanomaterial amplified immunoassays in the concentration ranges of 0.99 * 1043.98 * 109 cfu mL-1 and 103.97 * 107 cfu mL-1 which resulted in detection limits of 1.99 * 104 cfu mL-1 and 50 cfu mL-1, respectively. The developed methodology was then applied for E. coli quantification in water samples using nanomaterial modified assay. Same detection limit for E. coli was achieved for real sample analysis with a little decrease on the sensor signal. Cross-reactivity studies were conducted by testing Shigella, Salmonella spp., Salmonella typhimurium and Staphylococcus aureus on E. coli specific antibody surface that confirmed the high specificity of the developed immunoassays. The sensor surface could be regenerated multiple times which significantly reduces the cost of the system. Our custom-designed biosensor is capable of detecting bacteria with high sensitivity and specificity, and can serve as a promising tool for pathogen detection. PMID- 28992612 TI - Type of iconicity influences children's comprehension of gesture. AB - Children produce iconic gestures conveying action information earlier than the ones conveying attribute information (Ozcaliskan, Gentner, & Goldin-Meadow, 2014). In this study, we ask whether children's comprehension of iconic gestures follows a similar pattern, also with earlier comprehension of iconic gestures conveying action. Children, ages 2-4years, were presented with 12 minimally informative speech+iconic gesture combinations, conveying either an action (e.g., open palm flapping as if bird flying) or an attribute (e.g., fingers spread as if bird's wings) associated with a referent. They were asked to choose the correct match for each gesture in a forced-choice task. Our results showed that children could identify the referent of an iconic gesture conveying characteristic action earlier (age 2) than the referent of an iconic gesture conveying characteristic attribute (age 3). Overall, our study identifies ages 2-3 as important in the development of comprehension of iconic co-speech gestures, and indicates that the comprehension of iconic gestures with action meanings is easier than, and may even precede, the comprehension of iconic gestures with attribute meanings. PMID- 28992611 TI - Co-viewing supports toddlers' word learning from contingent and noncontingent video. AB - Social cues are one way young children determine that a situation is pedagogical in nature-containing information to be learned and generalized. However, some social cues (e.g., contingent gaze and responsiveness) are missing from prerecorded video, a potential reason why toddlers' language learning from video can be inefficient compared with their learning directly from a person. This study explored two methods for supporting children's word learning from video by adding social-communicative cues. A sample of 88 30-month-olds began their participation with a video training phase. In one manipulation, an on-screen actress responded contingently to children through a live video feed (similar to Skype or FaceTime "video chat") or appeared in a prerecorded demonstration. In the other manipulation, parents either modeled responsiveness to the actress's on screen bids for participation or sat out of their children's view. Children then viewed a labeling demonstration on video, and their knowledge of the label was tested with three-dimensional objects. Results indicated that both on-screen contingency and parent modeling increased children's engagement with the actress during training. However, only parent modeling increased children's subsequent word learning, perhaps by revealing the symbolic (representational) intentions underlying this video. This study highlights the importance of adult co-viewing in helping toddlers to interpret communicative cues from video. PMID- 28992613 TI - Is the reliability of 3D kinematics of young obese participants dependent on the hip joint center localization method used? AB - The aim of this study was to investigate if the test-retest reliability for three dimensional (3D) gait kinematics in a young obese population is affected by using either a predictive (Davis) or a functional (SCoRE) hip joint center (HJC) localization approach. A secondary goal was to analyze how consistent both methods perform in estimating the HJC position. A convenience sample of ten participants, two females and eight males with an age-based body mass index (BMI) above the 97th percentile (mean+/-SD: 34.2+/-3.9kg/m2) was recruited. Participants underwent two 3D gait analysis sessions separated by a minimum of one day and a maximum of seven days. The standard error of measurement (SEM) and the root mean square error (RMSE) of key kinematic parameters along with the root mean square deviation (RMSD) of the entire waveforms were used to analyze the test-retest reliability. To get an estimate of the consistency of both HJC localization methods, the HJC positions determined by both methods were compared to each other. SEM, RMSE, and RMSD results indicate that the HJC position estimations between both methods are not different and demonstrate moderate to good reliability to estimate joint kinematics. With respect to the localization of the HJC, notable inconsistencies ranging from 0 to 5.4cm were observed. In conclusion, both approaches appear equally reliable. However, the inconsistent HJC estimation points out, that accuracy seems to be a big issue in these methods. Future research should attend to this matter. PMID- 28992614 TI - Serum and Glucocorticoid Inducible Kinase 1-Sensitive Survival, Proliferation and Migration of Rhabdomyosarcoma Cells. AB - BACKGROUND/AIMS: Rhabdomyosarcoma, the most common pediatric soft tissue sarcoma, may show an intrinsic refractoriness to standard chemotherapy in advanced tumor stages, which is associated with poor prognosis. Cellular mechanisms conferring tumor cell survival and therapy resistance in many tumor types include the serum & glucocorticoid inducible kinase (SGK) 1 pathway, a kinase expressed ubiquitously with particularly strong expression in skeletal muscle and some tumor types. The present study explored whether SGK1 is expressed in rhabdomyosarcoma and, if so, whether this kinase impacts on tumor cell survival, proliferation and migration. Multiple in vitro techniques were used to study the role of SGK1 in rhabdomyosarcoma. METHODS: The Gene Chip(r) Human Genome U133 Plus 2.0 Array were employed to examine SGK1 transcriptional activity in healthy muscle and rhabdomyosarcoma tissue. SGK1 transcript levels were quantified in rhabdomyosarcoma cell lines RD (embryonal subtype) and RH30 (alveolar subtype) by RT-PCR, cell viability was measured using MTT assays. Clonal cell growth was assessed via colony forming assays and migration experiments were performed in a transwell system. RESULTS: SGK1 is expressed in embryonal and alveolar rhabdomyosarcoma tissue samples and in RD and RH30 rhabdomyosarcoma cell lines. Administration of EMD638683 - an inhibitor specific for SGK1 - decreased viability of RD and RH30 cells, enhanced the effects of the cytotoxic drug doxorubicin leading to reduced migration and decreased cell proliferation. CONCLUSIONS: SGK1 is expressed in rhabdomyosarcoma cells where it contributes to survival, therapy resistance, cell proliferation and migration. Thus, SGK1 inhibitors may be considered a therapeutic option for the treatment of therapy resistant rhabdomyosarcoma. PMID- 28992615 TI - Contributions and Future Directions for Structural Biology in the Study of Allergens. AB - Allergy is defined as an inappropriate immune response to something normally considered harmless. The symptomatic immune response is driven by IgE antibodies directed against allergens. The study of allergens has contributed significantly to our understanding of allergic disease in 3 main areas. First, identifying allergens as the cause of symptoms and developing allergen standards has led to many advances in exposure assessment and patient diagnostics. Second, a biochemical understanding of allergens has suggested a number of hypotheses related to the mechanisms of allergic sensitization. And finally, studies of allergen-antibody interactions have contributed to understanding the cross reactivity of allergens, mapping patient epitopes, and the development of hypoallergens. In this review, a few select cases are highlighted where structural biology, in particular, has contributed significantly to allergen research and provided new avenues for investigation. PMID- 28992616 TI - NS1 of H7N9 Influenza A Virus Induces NO-Mediated Cellular Senescence in Neuro2a Cells. AB - BACKGROUND/AIMS: The novel avian H7N9 influenza A virus has been detected in brain tissues and associated with central nervous system (CNS) symptoms in infected human and mice. Roles of its virulence factor, NS1 protein in influenza virus infected neuron has yet to be explored. METHODS: Nitric oxide (NO) release and inducible nitric oxide synthase (iNOS) expression in H7N9/NS1-expressed Neuro2a cells were detected by Griess test and western blotting. Cell proliferation rate of H7N9/NS1-expressing cells was recorded by Cell Counting Kit 8. Effects of H7N9/NS1 on cellular senescence were investigated by senescence associated beta-galactosidase (SA-beta-gal) staining, immunofluorescent staining of phosphorylated heterochromatin protein 1gamma (pHP1gamma) and qPCR analysis of IL-6 and IL-8. RESULTS: H7N9/NS1 in Neuro2a cells and primary cultured mouse cortical neurons increased the expression of iNOS and boosted NO release. Neuro2a cells constitutively expressing NS1 displayed a reduced proliferative ability, enhanced SA-beta-gal staining, increased level of IL-6 and IL-8 and a typical punctuate structure of pHP1gamma in nuclei. In addition, p38 MAPK was elevated in NS1-expressing Neuro2a cells. Reduced iNOS expression and subdued cellular senescence effect was found in p38 MAPK inhibitor-treated NS1-expressing Neuro2a cells. CONCLUSION: Our results suggest that H7N9/NS1 protein increases the iNOS expression and NO release in Neuro2a cells, which can induce cell growth arrest and cellular senescence. PMID- 28992617 TI - Iodine Promotes Tumorigenesis of Thyroid Cancer by Suppressing Mir-422a and Up Regulating MAPK1. AB - BACKGROUND/AIMS: Iodine may trigger tumorigenesis and development of thyroid carcinoma, but the mechanisms involved remained elusive. MicroRNA (MiRNAs) are known to be involved in each stage of cancer development; however, the role of miRNAs in iodine-induced tumorigenesis of thyroid carcinoma remained unknown. In this study, we aimed at investigating miRNA related signaling pathway in thyroid cancer cells. METHODS: Levels of miRNAs and mRNAs were determined using RT-qPCR and proteins were quantified by western blotting. Cell migration and proliferation were checked using Transwell assay and CCK8 assay respectively. Tumor xenografts in nude mice were established by subcutaneous injection of cancer cells. RESULTS: Mitogen activated protein kinase 1 (MAPK1) was significantly up-regulated, while miR-422a was down-regulated in thyroid cancer cells cultured with high iodine; miR-422a directly bound to the 3'UTR of MAPK1 mRNA. Moreover, miR-422a negatively regulated MAPK1 expression, and down regulated miR-422a promoted proliferation and migration of TPC-1 cells. In vivo studies also confirmed that iodine promoted tumor growth by suppressing miR-422a and up-regulating MAPK1. CONCLUSIONS: Our study illustrates a new pathway comprising iodine, miRNA and MAPK1, and defines a novel mechanism in thyroid cancer. PMID- 28992618 TI - Pregnancy Outcome among Women with Beta-Thalassemia Major in North Sardinia. PMID- 28992619 TI - Endoplasmic Reticulum Stress Induces HRD1 to Protect Alveolar Type II Epithelial Cells from Apoptosis Induced by Cigarette Smoke Extract. AB - BACKGROUND/AIMS: Cigarette smoking is a major risk factor of chronic obstructive pulmonary disease. This study aimed to examine the effects of cigarette smoke extract (CSE) on alveolar type II epithelial cells (AECII) and investigate the underlying mechanism. METHODS: Primary AECII were isolated from rat lung tissues and exposed to CSE. Apoptosis was detected by flow cytometry. Protein expression was detected by Western blot analysis. RESULTS: Primary rat AECII maintained morphological and physiological characteristic after 3 passages. CSE increased the expression of ER specific pro-apoptosis factors CHOP and caspase 12, and the phosphorylation of JNK in AECII. CSE activated ER stress signaling and increased the phosphorylation of PERK, eIF2alpha and IRE1. Furthermore, CSE induced the expression of Hrd1, a key factor of ER-associated degradation, in AECII. Knockdown of Hrd1 led to more than 2 fold increase of apoptosis, while overexpression of Hrd1 attenuated CSE induced apoptosis of AECII. CONCLUSIONS: Our results suggest that ER stress induces HRD1 to protect alveolar type II epithelial cells from apoptosis induced by CSE. PMID- 28992620 TI - Potential Ameliorative Effects of Qing Ye Dan Against Cadmium Induced Prostatic Deficits via Regulating Nrf-2/HO-1 and TGF-beta1/Smad Pathways. AB - BACKGROUND/AIMS: Cadmium (Cd) is an environmental pollutant with reproductive toxicity. Swertia mileensis is used in Chinese medicine for the treatment of prostatic deficits and named as Qing Ye Dan (QYD). This study was undertaken to investigate the potential protective effects of QYD against Cd-induced prostatic deficits. METHOD: Rat model of prostatic deficits was induced by 0.2 mg/kg/d CdCl2 subcutaneous injection for 15 days. The prostatic oxidative stress was evaluated by detecting the levels of malondialdehyde, nitric oxide, reduced/ oxidized glutathione, total sulfhydryl groups and enzymatic antioxidant status. The prostatic inflammation was estimated by testing the levels of pro inflammatory cytokines. The levels of epithelial-mesenchymal transition (EMT) markers E-cadherin, fibronectin, vimentin and alpha-smooth muscle actin were measured by qPCR analysis. Additionally, the prostatic expressions of transforming growth factor-beta1 (TGF-beta1), type I TGF-beta receptor (TGF betaRI), Smad2, phosphorylation-Smad2 (p-Smad2), Smad3, p-Smad3, Smad7, nuclear related factor-2 (Nrf-2), heme oxygenase-1 (HO-1), B-cell CLL/lymphoma (Bcl)-2 and Bcl-2-associated X protein (Bax) were measured by western blot assay. RESULTS: It was found that QYD ameliorated the Cd-induced prostatic oxidative stress and inflammation, attenuated prostatic EMT, inhibited the TGF-beta1/Smad pathway, increased Bcl-2/Bax ratio and enhanced the activity of Nrf-2/HO-1 pathway. CONCLUSION: These results showed that QYD could ameliorate Cd-induced prostatic deficits via modulating Nrf-2/HO-1 and TGF-beta1/Smad pathways. PMID- 28992621 TI - Protective Effects of Microrna-22 Against Endothelial Cell Injury by Targeting NLRP3 Through Suppression of the Inflammasome Signaling Pathway in a Rat Model of Coronary Heart Disease. AB - BACKGROUND/AIMS: This study aimed to identify the role of microRNA-22 (miR-22) in endothelial cell (EC) injury in coronary heart disease (CHD) by targeting NLRP3 through the inflammasome signaling pathway. METHODS: A total of 24 healthy male Sprague-Dawley (SD) rats were divided into normal and atherosclerosis groups. The atherosclerosis rats were assigned into blank, negative control (NC), miR-22 mimic, miR-22 inhibitor and miR-22 inhibitor + siNLRP3 groups. A luciferase reporter gene assay was used to detect the relationship between miR-22 and NLRP3. MiR-22 expression as well as NLRP3 and caspase-1 mRNA and protein expression were measured using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. The activity and apoptosis of coronary arterial endothelial cells (CAECs) were determined by MTT and Hoechst 33258. CAEC lumen formation was detected by a lumen formation assay. An enzyme-linked immunosorbent assay (ELISA) was used to detect IL-1beta, IL-6, IL-10 and IL-18 levels. RESULTS: The results indicated that the atherosclerosis group significantly decreased miR-22 expression but increased NLRP3 and caspase-1 mRNA and protein expression. The cell survival rate was significantly increased in the miR-22 mimic group and significantly reduced in the miR-22 inhibitor group. The miR-22 mimic group displayed a lower apoptosis rate and more cells with obvious lumen walls and numerous tubular structures, while cells in the miR-22 inhibitor group were unable to form lumen walls and had a scattered distribution compared to the blank group. The ELISA showed that IL-1beta, IL-6 and IL-18 levels were markedly decreased, while IL-10 was clearly increased in the miR-22 mimic group. In contrast, in the miR-22 inhibitor group, IL-1beta, IL-6 and IL-18 levels were significantly increased, and IL-10 levels were decreased. CONCLUSION: Our findings indicated that miR-22 could lower the levels of pro-inflammatory cytokines by inhibiting the NLRP3 inflammasome pathway, which suppresses CAEC apoptosis and protects CAECs in rats with CHD. PMID- 28992622 TI - A Subjective Rating Scale for Initial Assessment of Sudden Unilateral Sensorineural Hearing Loss. AB - OBJECTIVE: To examine the value of a subjective numerical rating scale (NRS) in the initial evaluation of patients suspected of suffering from unilateral sudden sensorineural hearing loss (SSNHL) until a formal audiogram is available. STUDY DESIGN: Prospective noncontrolled clinical study. METHODS: Thirty-one consecutive patients referred to the emergency department due to suspected unilateral SSNHL and with no other aural pathology by history or physical examination were enrolled. Patients were asked to characterize the severity of their hearing loss using an NRS of 1 (normal hearing) to 6 (complete deafness). SSNHL was defined as an SNHL of at least 30 dB over 3 consecutive frequencies that occurred in 3 days or less. A formal audiogram was obtained subsequently as soon as available. RESULTS: Twenty-four patients were treated with steroids and met the audiometric criteria of SSNHL. All scored their NRS as 3 or more. None of the 7 patients whose NRS grades were <=2.5 met the criteria for SSNHL. Two patients were treated with steroids although their hearing did not meet the audiometric criteria for SSNHL as the hearing loss was limited to 2 consecutive frequencies. The NRS score for both was <3. CONCLUSION: In addition to the patient's history and physical examination, a NRS can be a useful tool in the preliminary assessment of patients suspected of having SSNHL until audiometry becomes available. In the scale of 1 6, an NRS score of 3 or more reliably predicts the need to treat the patient with steroids according to the accepted criteria. PMID- 28992623 TI - Salvianolic Acid B Ameliorates Cognitive Deficits Through IGF-1/Akt Pathway in Rats with Vascular Dementia. AB - : BackgroundAims: Salvianolic acid B (SalB) is a natural polyphenolic compound enriched in Salvia miltiorrhiza Bunge. Our study was designed to explore the role of Sal B on cognitive impairment in vascular dementia (VD) model rats, as well as its possible molecular mechanisms. METHODS: Rats were randomly divided into four groups (n = 15 for each group): Control group, Sal B group (normal Sprague Dawley rats treated with Sal B), VD group and VD + Sal B group. The VD group rats were established by permanent bilateral common carotid artery occlusion (BCCAO). Animals in the Control and Sal B group received the same operation without bilateral common carotid arteries occlusion. The animals in Sal B group and VD + Sal B group received Sal B (20 mg/kg) orally once a day for consecutive 6 weeks. We investigated the effects of SalB on BCCAO-induced cognitive deficits rats models via the Morris water maze experiment. To explore the mechanisms of Sal B on cognitive function, we detected the expression of IGF-1, Akt and p-Akt, and the rate of cell apoptosis in CA1 region. RESULTS: Our results observed that hippocampal IGF-1 was decreased in VD model rats, while SalB reversed the alteration of IGF-1 levels. The expression of hippocampal Akt showed no significant difference between control and VD group, however, p-Akt level was significantly decreased in VD group. After 6 weeks of SalB treatment, p-Akt level was significantly increased. A large number of apoptotic neurons were found in VD model rats, while SalB prevented apoptosis of hippocampal neurons in CA1 region in VD model rats. CONCLUSION: SalB significantly ameliorated cognitive deficits in BCCAO-induced VD model rats. The potential mechanism underlying the protective effects may be mediated through IGF-1/Akt pathway. PMID- 28992624 TI - How to Train to Discharge a Dermatology Outpatient: A Review. AB - BACKGROUND/AIMS: The decision to discharge is a critical and common outpatient consultation event. However, little guidance exists over how discharge decision making can be taught. We aimed to provide educational recommendations concerning outpatient discharge decision-making. METHODS: Recommendations were drawn from prior interviews with 40 consultant dermatologists and 56 dermatology outpatients, and from the "traffic light" design discharge information checklist, developed using the Delphi technique. RESULTS: The key strategies to follow to appropriately manage the outpatient discharge process are: to warn patients in advance, to understand patients' agendas, to allow extra time for the discharge process, to prepare patients to self-manage, to provide a "safety net" and provide the GP with a clear management plan. Aspects to be considered include patient mobility, presence of carer, type of employment, diagnostic certainty, and use of the checklist or guidelines. Key training aspects include teaching structured thought processes when discharging, discharging according to context, developing communication and negotiation skills, avoiding decision biases and encouraging good interprofessional collaboration. Training should include the consideration of the possibility of discharge at each consultation. Novel training strategies have been developed on how to appropriately manage the outpatient discharge process, including involving and informing patients. These strategies focus on safe decision-making, being patient-centred and organizing an efficient health care service framework. CONCLUSION: Structured outpatient discharge training for dermatologists is now possible, based on information from detailed doctor- and patient-based qualitative studies. PMID- 28992625 TI - B Chromosome Variants of the Grasshopper Xyleus discoideus angulatus Are Potentially Derived from Pericentromeric DNA. AB - B chromosomes, extra elements present in the karyotypes of some eukaryote species, have been described in the grasshopper Xyleus discoideus angulatus. Although some studies have proposed an autosomal origin of the B chromosome in X. d. angulatus, little is known about its repetitive DNA composition and evolutionary dynamics. The aim of the present work was to shed light on the B chromosome evolution in X. d. angulatus by cytogenetic analysis of 27 populations from Pernambuco and Ceara states (Brazil). The frequency of B chromosomes in the different populations was determined, and chromosome measurements and fluorescence in situ hybridization (FISH) with C0t-DNA and telomeric and B chromosome sequences were performed in cells from B-carrying individuals. The results revealed variations in B chromosome prevalence among the populations and showed that some B chromosomes were smaller in certain populations. FISH produced similar patterns for the C0t-DNA probe in all hybridized individuals, whereas telomeric and B chromosome probes, obtained by microdissection, exhibited variations in their distribution. These results indicate the presence of 3 morphotypes of B chromosomes in X. d. angulatus, with variation in repetitive DNA composition during their evolution. In this species, B chromosomes have an intraspecific origin and probably arose from the pericentromeric region of A chromosomes. PMID- 28992626 TI - Multiple Sclerosis and Clinical Gait Analysis before and after Fampridine: A Systematic Review. AB - BACKGROUND: Gait impairment is one of the most disabling symptoms in people with multiple sclerosis (PwMS). Fampridine, has demonstrated a positive effect on gait speed in PwMS after 14 days of treatment but the long-term effects have not yet been demonstrated. This study reviews the long-term effects of fampridine on gait in PwMS. SUMMARY: This systematic review was conducted according to the PRISMA statement. Studies were considered long term if treatment exceeded 28 days. From the 498 studies identified, 18 (2,200 patients) fulfilled all eligibility criteria. Only 3 studies followed-up patients for >1 year and one of these showed a non-significant improvement in the gait speed. Key Messages: Fampridine seems to be beneficial at improving gait speed in PwMS in the long term. Further long term studies are needed on related gait and functional parameters. PMID- 28992627 TI - H3 Relaxin Protects Against Myocardial Injury in Experimental Diabetic Cardiomyopathy by Inhibiting Myocardial Apoptosis, Fibrosis and Inflammation. AB - BACKGROUND/AIMS: Apoptosis, fibrosis and NLRP3 inflammasome activation are involved in the development of diabetic cardiomyopathy (DCM). Human recombinant relaxin-3 (H3 relaxin) is a novel bioactive peptide that inhibits cardiac injury; however, whether H3 relaxin prevents cardiac injury in rats with DCM and the underlying mechanisms are unknown. METHODS: To investigate the effect of H3 relaxin on DCM, we performed a study using H3 relaxin treatment in male Sprague Dawley (SD) rats with streptozotocin (STZ)-induced diabetes (DM). We measured apoptosis, fibrosis and NLRP3 inflammasome markers in the rat hearts four and eight weeks after the rats were injected with STZ (65 mg/kg) by western blot analysis. Subsequently, 2 or 6 weeks after the STZ treatment, the rats were treated with H3 relaxin [2 ug/kg/d (A group) or 0.2 ug/kg/d (B group)] for 2 weeks. Cardiac function was evaluated by echocardiography to determine the extent of myocardial injury in the DM rats. The protein levels of apoptosis, fibrosis and NLRP3 inflammasome markers were used to assess myocardial injury. In addition, we determined the plasma levels of IL-1beta and IL-18 using a Milliplex MAP Rat Cytokine/Chemokine Magnetic Bead Panel kit. RESULTS: The protein expression of cleaved caspase-8, caspase-9 and caspase-3 as well as fibrosis markers increased at 4 and 8 weeks in the STZ-induced diabetic hearts compared with the levels in the control group. Furthermore, the NLRP3 inflammasome was substantially activated in STZ-induced diabetic hearts, leading to increased IL 1beta and IL-18 levels. Compared with the DM group, the A group exhibited substantially better cardiac function. The protein levels of apoptosis markers were attenuated by H3 relaxin, indicating that H3 relaxin inhibited myocardial apoptosis in the hearts of diabetic rats. The protein expression of fibrosis markers was inhibited by H3 relaxin. Additionally, the protein expression and activation of the NLRP3 inflammasome were also effectively attenuated by H3 relaxin. CONCLUSIONS: This study is the first to demonstrate that H3 relaxin plays an anti-apoptotic, anti-fibrotic and anti-inflammatory role in DCM. PMID- 28992628 TI - Ultrastructural, Confocal and Viscoelastic Characteristics of Whole Blood and Plasma After Exposure to Cadmium and Chromium Alone and in Combination: An Ex Vivo Study. AB - BACKGROUND/AIMS: Heavy metal pollution is increasing in the environment, contaminating water, food and air supplies. This can be linked to many anthropogenic activities. Heavy metals are absorbed through the skin, inhalation and/or orally. Irrespective of the manner of heavy metal entry in the body, the blood circulatory system is potentially the first to be affected following exposure and adverse effects on blood coagulation can lead to associated thrombotic disease. Although the plasma levels and the effects of cadmium (Cd) and chromium (Cr) on erythrocytes and lymphocytes have been described, the environmental exposure to heavy metals are not limited to a single metal and often involves metal mixtures, with each metal having different rates of absorption, different cellular, tissue, and organ targets. Therefore the aim of this study is to investigate the effects of the heavy metals Cd and Cr alone and whether Cr synergistically increases the effect of Cd on physiological important processes such as blood coagulation. METHODS: Human blood was exposed to the heavy metals ex vivo, and thereafter morphological analysis was performed with scanning electron- and confocal laser scanning microscopy (CLSM) in conjunction with thromboelastography(r). RESULTS: The erythrocytes, platelets and fibrin networks presented with ultrastructural changes, including varied erythrocytes morphologies, activated platelets and significantly thicker fibrin fibres in the metal-exposed groups. CLSM analysis revealed the presence of phosphatidylserine on the outer surface of the membranes of the spherocytic erythrocytes exposed to Cd and Cr alone and in combination. The viscoelastic analysis revealed only a trend that indicates that clots that will form after heavy metal exposure, will likely be fragile and unstable especially for Cd and Cr in combination. CONCLUSION: This study identified the blood as an important target system of Cd and Cr toxicity. PMID- 28992631 TI - Methodological Quality Assessment of Meta-Analyses of Hyperthyroidism Treatment. AB - Hyperthyroidism is a common condition that is associated with increased morbidity and mortality. A number of meta-analyses (MAs) have assessed the therapeutic measures for hyperthyroidism, including antithyroid drugs, surgery, and radioiodine, however, the methodological quality has not been evaluated. This study evaluated the methodological quality and summarized the evidence obtained from MAs of hyperthyroidism treatments for radioiodine, antithyroid drugs, and surgery. We searched the PubMed, EMBASE, Cochrane Library, Web of Science, and Chinese Biomedical Literature Database databases. Two investigators independently assessed the meta-analyses titles and abstracts for inclusion. Methodological quality was assessed using the validated AMSTAR (Assessing the Methodological Quality of Systematic Reviews) tool. A total of 26 MAs fulfilled the inclusion criteria. Based on the AMSTAR scores, the average methodological quality was 8.31, with large variability ranging from 4 to 11. The methodological quality of English meta-analyses was better than that of Chinese meta-analyses. Cochrane reviews had better methodological quality than non-Cochrane reviews due to better study selection and data extraction, the inclusion of unpublished studies, and better reporting of study characteristics. The authors did not report conflicts of interest in 53.8% meta-analyses, and 19.2% did not report the harmful effects of treatment. Publication bias was not assessed in 38.5% of meta-analyses, and 19.2% did not report the follow-up time. Large-scale assessment of methodological quality of meta-analyses of hyperthyroidism treatment highlighted methodological strengths and weaknesses. Consideration of scientific quality when formulating conclusions should be made explicit. Future meta-analyses should improve on reporting conflict of interest. PMID- 28992629 TI - alpha-Lipoic Acid Promotes Neurological Recovery After Ischemic Stroke by Activating the Nrf2/HO-1 Pathway to Attenuate Oxidative Damage. AB - BACKGROUND/AIMS: Alpha-lipoic acid (alpha-LA) has been demonstrated to be protective against cerebral ischemia injury. Herein, we investigate the neuroprotective effect and underlying mechanisms of alpha-LA. METHODS: In vivo study, alpha-LA was administered intravenously upon reperfusion of transient middle cerebral artery occlusion. Garcia score was used to evaluate neurologic recovery. Infarct volume was examined by TTC staining, and oxidative damage was evaluated by ELISA assay. In an in vitro study, neurons were pretreated with alpha-LA at different doses and then subjected to OGD. Lentiviral vectors were applied to knockdown nuclear factor-erythroid 2-related factor-2 (Nrf2) or heme oxygenase-1 (HO-1). Cell viability was measured using CCK8. Protein expression was evaluated using western blot, and immunofluorescence staining was assessed. RESULTS: alpha-LA significantly reduced the infarct volume, brain edema, and oxidative damage and promoted neurologic recovery in rats. Pretreatment of alpha LA caused an obvious increase in cell viability and a decrease in intracellular reactive oxygen species. Western blot analyses and immunofluorescence staining demonstrated a distinct increase in Nrf2 and HO-1 protein expression. Conversely, knockdown of Nrf2 or HO-1 resulted in the down-regulation of HO-1 protein and inhibited the neuroprotective effect of alpha-LA. CONCLUSION: alpha-LA treatment is neuroprotective and promotes functional recovery after ischemic stroke by attenuating oxidative damage, which is partially mediated by the Nrf2/HO-1 pathway. PMID- 28992630 TI - Ion sieving in graphene oxide membranes via cationic control of interlayer spacing. AB - Graphene oxide membranes-partially oxidized, stacked sheets of graphene-can provide ultrathin, high-flux and energy-efficient membranes for precise ionic and molecular sieving in aqueous solution. These materials have shown potential in a variety of applications, including water desalination and purification, gas and ion separation, biosensors, proton conductors, lithium-based batteries and super capacitors. Unlike the pores of carbon nanotube membranes, which have fixed sizes, the pores of graphene oxide membranes-that is, the interlayer spacing between graphene oxide sheets (a sheet is a single flake inside the membrane)-are of variable size. Furthermore, it is difficult to reduce the interlayer spacing sufficiently to exclude small ions and to maintain this spacing against the tendency of graphene oxide membranes to swell when immersed in aqueous solution. These challenges hinder the potential ion filtration applications of graphene oxide membranes. Here we demonstrate cationic control of the interlayer spacing of graphene oxide membranes with angstrom precision using K+, Na+, Ca2+, Li+ or Mg2+ ions. Moreover, membrane spacings controlled by one type of cation can efficiently and selectively exclude other cations that have larger hydrated volumes. First-principles calculations and ultraviolet absorption spectroscopy reveal that the location of the most stable cation adsorption is where oxide groups and aromatic rings coexist. Previous density functional theory computations show that other cations (Fe2+, Co2+, Cu2+, Cd2+, Cr2+ and Pb2+) should have a much stronger cation-pi interaction with the graphene sheet than Na+ has, suggesting that other ions could be used to produce a wider range of interlayer spacings. PMID- 28992632 TI - The Effects of Selenium Supplementation on Glucose Metabolism and Lipid Profiles Among Patients with Metabolic Diseases: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. AB - This systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to summarize the effect of selenium administration on glucose metabolism and lipid profiles among patients with diseases related to metabolic syndrome (MetS). We searched the following databases up to May 2017: MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials. The relevant data were extracted and assessed for quality of the studies according to the Cochrane risk of bias tool. Data were pooled using the inverse variance method and expressed as standardized mean difference (MDs) with 95% confidence intervals (95% CI). Five studies were included in the meta-analyses. The results showed that selenium supplementation significantly reduced insulin levels (SMD 0.42; 95% CI, -0.83 to -0.01) and increased quantitative insulin sensitivity check index (QUICKI) (SMD 0.83; 95% CI, 0.58 to 1.09). Selenium supplementation had no beneficial effects on other glucose homeostasis parameters, such as fasting plasma glucose (FPG) (SMD -0.29; 95% CI, -0.73 to 0.15), homeostasis model assessment of insulin resistance (HOMA-IR) (SMD -0.80; 95% CI, -1.58 to 0.03), and lipid profiles, such as triglycerides (SMD -0.42; 95% CI, -0.83 to 0.01), VLDL- (SMD -0.42; 95% CI, -0.83 to -0.01), total- (SMD -0.42; 95% CI, 0.83 to -0.01), LDL- (SMD 0.02; 95% CI, -0.20 to 0.24), and HDL-cholesterol (SMD 0.16; 95% CI, -0.06 to -0.38). Overall, this meta-analysis showed that selenium administration may lead to an improvement in insulin and QUICKI, but did not affect FPG, HOMA-IR, and lipid profiles. PMID- 28992633 TI - Endoscopic mucosa-submucosal clip closure method. PMID- 28992634 TI - Deep endoscopic submucosal dissection of a refractory tracheoesophageal fistula using clip-and-line traction: a successful closure. PMID- 28992635 TI - Anchoring the snare tip using a small incision in the submucosa facilitates en bloc endoscopic mucosal resection for sporadic duodenal adenomas. PMID- 28992636 TI - Endoscopic removal of a proximally migrated biliary stent using a novel gooseneck snare: the "EndoCowboy". PMID- 28992637 TI - Endoscopic ultrasound-guided gallbladder drainage to facilitate biliary rendezvous for the management of cholangitis due to choledocholithiasis. PMID- 28992638 TI - Percutaneous cecostomy with fully covered self-expandable metal stent for initial management of severe malignant colon obstruction. PMID- 28992639 TI - Open peroral endoscopic myotomy for achalasia with sigmoid-shaped esophagus. PMID- 28992640 TI - Electronic hydraulic lithotripsy by antegrade digital cholangioscopy through endoscopic ultrasound-guided hepaticojejunostomy. PMID- 28992641 TI - Circumferential rectal laterally spreading tumor resected by endoscopic submucosal dissection in a Western center. PMID- 28992642 TI - Endoscopic drainage of an infected post-surgical abdominal fluid collection using a lumen-apposing metal stent. PMID- 28992643 TI - [Treatment of ureteropelvic junction obstruction in adult age]. AB - Ureteropelvic stenosis, also known as ureteropelvic junction obstruction, is an obstruction in the region of the pyeloureteral junction resulting in a urinary discharge disorder of the renal pelvis, which requires treatment.Since the first description of pyeloplasty by Trendelenburg in 1886 and the successful establishment of open pyeloplasty by Anderson and Hynes in 1949, the treatment strategies for ureteropelvic junction obstruction have developed considerably, especially in the last two decades. Although open pyeloplasty is still considered to be the gold standard, this concept is supplemented by modern minimally invasive techniques today. These include laparoscopic pyeloplasty, laparoscopic single-site pyeloplasty, robot-assisted pyeloplasty, robot-assisted single-site pyeloplasty, and endopyelotomy. This article provides an overview of the different treatment strategies for ureteropelvic junction obstruction as well as the complication management of pyeloplasty in adult age. PMID- 28992644 TI - Neurovisual Assessment in Children with Ataxia Telangiectasia. AB - AIM: Visual impairment is present in almost all patients with ataxia telangiectasia (AT) and, due to their early onset, constitute an important disabling aspect of the syndrome: the quality of vision is limited by dyspraxia and oculomotor abnormal movements. The purpose of this observational study was to describe visual disorders, notably oculomotor impairment, in a sample of children with AT. METHODS: Fifteen AT patients (mean age 12 years and 4 months) underwent a neurovisual evaluation, particularly focused on oculomotor functions (fixation, smooth pursuit, saccades, and abnormal ocular movements). We compared the visual profile obtained with that described using the International Cooperative Ataxia Rating Scale (ICARS) subscale of oculomotor dysfunction. RESULTS: Refractive errors were seen in eight patients and strabismus in three. Major oculomotor findings were fixation abnormalities (6/15), saccadic impairment (15/15), and abnormal smooth pursuit (14/15). Abnormal ocular movements were seen in 13/15 (saccadic intrusion in 8 and nystagmus in 5). Using ICARS scale, 13/15 children presented gaze-evoked nystagmus, 4/15 a clearly saccadic pursuit, and 11/15 dysmetria of saccades. DISCUSSION: We propose a clinical neurovisual evaluation, which could be integrated with ICARS scores in the study of oculomotor involvement in AT pediatric patients. We strongly recommend the empowerment of visual functions to slow down progressive global disability of these patients. PMID- 28992645 TI - Effects of Tirofiban on Random Skin Flap Survival in Rats. AB - BACKGROUND: Tirofiban is a glycoprotein IIb/IIIa receptor antagonist that is widely used clinically. In the present study, we investigated whether tirofiban promotes flap survival in rat random skin flap model. METHODS: "McFarlane flaps" models were developed in 60 male rats. The rats were divided into a tirofiban treated group (n = 30) and a saline-treated group (n = 30). The flap surviving rate was calculated 7 days after surgery. Tissue samples were collected and subjected to histopathological evaluation. Lead oxide-gelatin angiography and immunohistochemical staining analysis were taken to evaluate angiogenesis. Analysis of oxidative stress was performed by measuring the activity of superoxide dismutase (SOD) and malondialdehyde (MDA). RESULTS: Compared with controls, the tirofiban-treated groups exhibited significantly larger mean areas of flap survival, significantly increased SOD activity, and vascular endothelial growth factor (VEGF) expression, and significantly reduced MDA level. Hematoxylin and eosin staining revealed that naringin promoted angiogenesis and inhibited inflammation. CONCLUSION: These findings demonstrate that tirofiban increases flap survival of random skin flaps in rats. PMID- 28992646 TI - First Experiences with Incisional Negative Pressure Wound Therapy in a High-Risk Poststernotomy Patient Population treated with Pectoralis Major Muscle Flap for Deep Sternal Wound Infection. AB - BACKGROUND: Radical debridement and wound closure with vascularized flaps has become a standard procedure in the treatment of deep sternal wound infections. Negative pressure incision management systems have been proven to diminish wound infections after sternotomy. In this study, the utility of Prevena Incision Management System (KCI Licensing Inc.) was evaluated in obese patients who received unilateral pectoralis major flap for the treatment of deep sternal wound infections. METHODS: The outcome and wound-related complication rates of 19 obese patients (mean body mass index, 33.7) treated for deep sternal wound infection with pectoralis major muscle flap in combination with Prevena between 2011 and 2016 were compared with 28 obese patients treated with conventional wound dressing only between 2000 and 2010. RESULTS: In patients additionally treated with Prevena, significantly fewer surgical revisions due to wound-related complications were necessary as compared with patients who received conventional wound dressing (5.3 vs. 32.1%, p = 0.034). A significantly shorter ICU length of stay (median 0 vs. 3.5 days, p < 0.001) and a trend toward shorter length of hospitalization (median 14 vs. 19.5 days after pectoralis major flap) could be observed. CONCLUSION: The application of Prevena significantly reduced revision surgery rates in obese patients treated with unilateral pectoralis major flap for deep sternal wound infections. PMID- 28992647 TI - Surgical Duration Impacts Venous Thromboembolism Risk in Microsurgical Breast Reconstruction. AB - BACKGROUND: Increased surgical duration can impact patient outcomes and operative efficiency metrics. In particular, there are studies suggesting that increased surgical duration can increase the risk of venous thromboembolism (VTE). One of the longer duration plastic surgery procedures commonly performed is microsurgical breast reconstruction. With the widening indications for multiple and "stacked" free flaps to reconstruct breasts, we endeavored to assess (1) the relationship between duration of microsurgical breast reconstruction and VTE; and (2) determine if a threshold operative time exists that connotes VTE higher risk. METHODS: Patients from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) between 2005 and 2014 who underwent microsurgical breast reconstruction were identified by Current Procedural Terminology code. Three models of multivariate logistic regression were used to characterize the adjusted risk for VTE by operative duration, bilaterality, the length of stay, and patient demographics. RESULTS: A total of 4,782 patients who underwent microsurgical breast reconstruction were identified. Overall VTE incidence was 1.13%. The mean operative duration was 8:31 hours:minutes (standard deviation: 2:59). Operative duration was statistically associated with VTE in continuous, quintile, and dichotomized risk models. Beyond an operative duration of 11 hours, adjusted VTE risk increases fourfold corresponding to a number needed to harm of 45.8. CONCLUSIONS: Increasing surgical duration heightens the risk of VTE in microsurgical breast reconstruction. Increasing body mass index and age enhances this VTE risk. Moreover, limiting surgical duration to 11 hours or less can decrease VTE risk by fourfold vis-a-vis baseline. LEVEL OF EVIDENCE: Risk, II. PMID- 28992648 TI - Application of Indocyanine Green in Flap Surgery: A Systematic Review. AB - BACKGROUND: The vascularization of the distal portions of transferred tissue represents the most critical factor in the success of reconstructive surgery. In recent years, indocyanine green (ICG) fluorescence imaging techniques have been applied during surgery to evaluate flap perfusion. However, this investigation has found that there is little consensus regarding the standard dose of ICG as well as the pre-operative requirements of ICG allergy testing. The aim of this study is to summarize the applications of ICG to tissue transfers and safe dosing practices and to provide insight to the possible adverse effects of ICG on flap surgery with the goal of helping clinicians apply ICG safely and efficiently to tissue transfer procedures. METHODS: A literature search was performed using, Wiley InterScience, and Springer with the key words, 'Flap,' 'indocyanine green,' 'surgery,' and related mesh words for all publications between 2005 and 2015. Title and abstract screening was performed using predefined in- and exclusion criteria. RESULTS: Seventy-three articles were included. These were classified as "application of ICG in flap surgery" and "the security of applying ICG in flap surgery". CONCLUSIONS: ICG fluorescence imaging preoperatively facilitates the detection of perforators in tissue flaps with thickness <20 mm, aids in the evaluation of flap microcirculation and perfusion, and allows surgeons to select dominant cutaneous nerves while evaluating the quality of vascular anastomoses and locating thromboses. The literature also concluded that potential allergic reactions to ICG should be taken into consideration. PMID- 28992649 TI - Stent Thrombosis. AB - The most dreaded complication with percutaneous coronary intervention with stents, either bare-metal or drug-eluting stents is stent thrombosis (ST) and it has a significant detrimental effect on the outcome for the patient. The initial attempts at intervention with bare-metal stents had much higher rates of ST compared with what is currently prevailing in the modern interventional world. Significant changes with respect to the stent technology, pharmacology, and most importantly our understanding of this phenomenon have decreased the risk of ST. There are many factors that can be performed to minimize the risk of ST and this review will describe the incidence, pathophysiology, and contributing risk factors to ST. PMID- 28992650 TI - Platelet CLEC-2: Roles Beyond Hemostasis. AB - C-type lectin-like receptor 2 (CLEC-2) has been identified on the surface of platelets as a receptor for a platelet activating snake venom, rhodocytin/aggretin. CLEC-2 belongs to a C-type lectin superfamily and binds to a sialoglycoprotein, podoplanin, in vivo. Platelets play a crucial role in hemostasis and thrombosis, but recent studies have uncovered multiple roles of platelets beyond hemostasis in physiology and pathology. The interaction between platelet CLEC-2 and podoplanin is the key to several roles of platelets beyond hemostasis. The spatial and temporal expression patterns of podoplanin regulate vascular/lymphatic development, maintenance of vascular integrity, tissue regeneration, and some pathological processes including tumor metastasis and thromboinflammation. CLEC-2 facilitates blood/lymphatic vessel separation during embryonic development by binding to podoplanin on lymphatic endothelial cells. The leakage of platelets from hyperpermeable vessels for maintaining vascular integrity during inflammation depends on CLEC-2. During wound healing, the expression of podoplanin in keratinocytes is upregulated, which helps in the process. Podoplanin is expressed on the surface of tumor cells and facilitates hematogenous metastasis by inducing platelet aggregation through CLEC-2. During thrombotic processes, such as development of deep vein thrombosis, podoplanin is upregulated on unknown cells in the vessel wall in the area of inflammation, facilitates thrombus formation, and promotes further inflammation by binding to CLEC-2. In this article, the roles of platelets beyond hemostasis are comprehensively reviewed. PMID- 28992651 TI - Localization of Exogenous Mesenchymal Stem Cells in a Pig Model of Lung Transplantation. AB - BACKGROUND: Mesenchymal stem cells (MSCs) have a great potential for the treatment of acute lung injury. This study provides a detailed immunohistochemical and stereological analysis of the localization and distribution of exogenous MSC in a pig model of lung transplantation after intravascular or endobronchial application. METHODS: MSC derived from human bone marrow were labeled by DiI and administered intravascularly or endobronchially to the lungs of donor pigs after a period of 3 hours warm and 3 hours cold ischemia. The left lung was transplanted to a recipient pig and reperfused for 4 hours before fixation. The right donor lung was fixed for microscopic analysis directly after the ischemia time. RESULTS: After both administration routes, a similar number of exogenous MSC was found in the lungs. Within each animal, the heterogeneity of MSC distribution was high both with respect to left and right lung as well as to the different lobes of each lung. After endobronchial application, MSC were found in alveolar and bronchial/bronchiolar lumen, whereas after intravascular administration, they were mainly observed in blood vessels. CONCLUSION: Although the administration of exogenous MSC is possible by endobronchial or intravascular application, it yields a heterogeneous distribution in the lungs which may warrant strategies to improve a more homogeneous distribution. PMID- 28992653 TI - Surgical Outcome of Colon Interposition in Esophageal Cancer Surgery: Analysis of Risk Factors for Conduit-Related Morbidity. AB - BACKGROUND: We aimed to assess the feasibility, surgical outcomes, and conduit related complications of colon interposition in patients with esophageal cancer. METHODS: Patients with esophageal cancer who underwent colon interposition for esophageal reconstruction between June 2000 and June 2013 were retrospectively reviewed. RESULTS: A total of 67 consecutive patients (mean age, 62.2 +/- 7.9 years) were enrolled. During this time period, 944 patients underwent esophageal reconstruction using gastric conduit. Twelve patients (17.9%) also received neoadjuvant chemoradiotherapy (nCRT). The median follow-up duration was 44 months (range, 1-168 months); median survival duration was 63 months (range, 1-168 months); and 3- and 5-year overall survival rates were 61.6 and 49.4%, respectively. A total of 43 patients (64.2%) experienced at least 1 postoperative morbidity. According to the Clavien-Dindo grading system, 36 patients (54%) experienced postoperative morbidity of higher than Grade III. Pulmonary complications were most commonly observed complications among the patients (18 patients, 26.9%). Anastomosis site leakage developed in 11 patients (16.4%), and 3 of these patients (6.0%) eventually experienced graft failure. On multivariate analysis, nCRT was determined as a significant risk factor for conduit-related complications (leakage, graft failure, fistula, and stricture). CONCLUSION: Colon interposition is associated with relatively high complication rates, whereas nCRT is associated with conduit morbidity. PMID- 28992652 TI - Chemoradiation Therapy Followed by Surgery in the Treatment of Locoregionally Advanced Non-Small Cell Lung Cancer. AB - BACKGROUND: The aim of this study was to explore the feasibility of surgery after two induction cycles of cisplatin-docetaxel followed by concomitant 40 Gy chemoradiation in the treatment of initially unresectable stage III non-small cell lung cancer (NSCLC; TAXCIS protocol), and to evaluate overall survival (OS) and recurrence-free survival (RFS) and recurrence risk factors over a larger cohort of patients with a subgroup analysis of patients treated by pneumonectomy. METHODS: Between 2004 and 2014, a total of 37 patients were treated. Only patients responding to induction treatment were included. RESULTS: We operated on 32 stage IIIA and 5 stage IIIB patients. We performed 12 pneumonectomies, 1 bilobectomy, and 23 lobectomies. Status ypT0N0 was obtained for 35% of the patients. Surgery was considered R0 in 86% of the cases. Postoperative morbidity was 21.6% with a mortality of 10.8% (25% after pneumonectomy). OS was 50% at 5 years. The median RFS was 50 months. RFS was 47% at 5 years. Local or locoregional recurrence was diagnosed in 10.8% of the patients, and distant metastasis in 35.1%. Recurrence risk factors were pneumonectomy (p = 0.001) and a histologically incomplete response (p = 0.04). CONCLUSION: The TAXCIS protocol followed by surgery is feasible for initially unresectable NSCLC stage IIIA and B patients. Benefit was noted in responding lesions with better OS and PFS, except after pneumonectomy. PMID- 28992655 TI - ? PMID- 28992654 TI - Long-Term Survival after Salvage Surgery for Local Failure after Definitive Chemoradiation Therapy for Locally Advanced Non-small Cell Lung Cancer. AB - BACKGROUND: The incidence of local failure and residual tumor after definitive chemoradiation therapy (dCRT) for locally advanced non-small-cell lung cancer remains high, irrespective of applied radiation dose (>59 Gy). So-called salvage surgery has been suggested as a feasible treatment option after failure of definitive chemoradiation for locally advanced non-small cell lung cancer (NSCLC). Experience with salvage lung surgery (SLS) is limited, and long-term survival is rarely reported. Patient selection criteria for surgical lung salvage are not defined. The aim of this study was to assess postoperative survival and perioperative morbidity/mortality to identify prognostic factors and to define patient selection criteria. PATIENTS AND METHODS: Records of 13 consecutive patients with locally advanced NSCLC, who underwent SLS at a single institution between March 2011 and November 2016, were reviewed. Descriptive statistics were applied for patient characteristics and surgical and oncological outcome. Survival rates were calculated using the Kaplan-Meier method and were compared with the long-rank test. RESULTS: All patients initially received curative-intent definitive chemoradiation with median radiation doses of 66 Gy (range 59.4-72) and concurrent platinum-based chemotherapy. Clinical tumor stage before definitive chemoradiation was IIIA in 9, IIIB in 3, IV in 1 patients. Median interval between definitive chemoradiation and salvage surgery was 6.7 months. Perioperative morbidity and 30-days-mortality was 38% and 7.7%, respectively. The median postoperative survival and estimated 5-year survival rate were 29.7 months and 46%, respectively. CONCLUSION: SLS in patients with locally advanced non small cell lung surgery following dCRT is feasible, prolongs long-term survival and allows local tumor control. Selection criteria remain undefined and patients should be considered surgical candidates during multidisciplinary team conference. PMID- 28992656 TI - [SOP - Standarized procedures in diagnostics and therapies of periocular basal cell carcinoma]. AB - The basal cell carcinoma (BCC) is the malignant eye tumor with the highest incidence. The aim of this article is to present a systematic and standardized approach to diagnose, treat and care periocular basal cell carcinoma. Interpretation of clinical signs, diagnostic tools to identify periocular BCC and interpretation lead to the appropriate choice of therapy. Surgical removal with a histological R0 resection is an important component of therapy options in this disease and includes the microsurgical excision into healthy tissue and the subsequent covering of the defect. Alternative treatment options are targeted therapies with hedgehog inhibitors and beam radiation in excessive basal cell carcinoma. Also, aftercare of patients with basal cell carcinoma follows the treatment. A special focus of this article is the treatment of locally extensive and metastasized BCC and the national S2 guidelines of this tumor. PMID- 28992657 TI - [Competing Validity of Developmental Diagnostic in School Entry Examination: Results of a Census in an Upper Bavarian District]. AB - AIM OF THE STUDY: Evaluation of the concurrent validity of a modified Bavarian model (BM) compared to the social-paediatric screening of developmental status for school entry (SOPESS) as a reference tool. METHODS: A total of 407 preschoolers to be enrolled for the school year 2015 in an Upper Bavarian District were examined by BM and SOPESS. As a measure of the concurrent validity, the Kappa by Cohen (K) was used. RESULTS: The agreement of both instruments was moderate and was less pronounced for single dimensions than globally. The agreement in the dimensions of "prepositions" vs. "grammatism" (K=0.46) was highest and for the dimensions "numbers and quantities" vs. "calculus" (K=0.05). Stratification by age, gender, nationality and mode of the study programs had no significant influence on the strength of the effects. CONCLUSION: The moderate agreement between the 2 instruments raises the question of the validity of BM used so far in school enrollment examinations. PMID- 28992658 TI - [The Ploner Model for the School Entry Screening is a Role Model for the Future]. AB - BACKGROUND: The Ploner Model is a stepwise-selective model, similar to the one practised in all of Bavaria since 2008. It was already developed in 2002/2003 for the school entry screening and has been in use since then. Such models are intermittently criticized since not each child is seen by a doctor. METHODS: The procedure and data of the Ploner Model are analyzed and put into a wider context within Germany and beyond. The current programs in place are therefore categorized into 3 groups and compared with regard to public heath ethics criteria. The primary endpoint is the need for special schooling or assistance. RESULTS: From 2003 to 2016, 1475-1045 children per year before school entry were checked by the pediatric health team of the county health department consisting of 2.1 full time equivalents of medical assistants and 1.5 fulltime equivalent pediatricians having other routine duties. Applying a stepwise-selective model, for children with special needs, 45-60 min instead of the usual 15 min per child were available. The roster consisting of a questionnaire for parents with a comment section for the daycare staff, a health and developmental check by the medical assistants and a detailed catalogue of inclusion criteria allowed to only examine 28-41% of the cohort by a pediatrician. The percentage of children needing further special care was within the mean of the entire cohort of the federal state of Schleswig-Holstein. CONCLUSION: A stepwise-selective procedure is warranted for the sake of efficiency and public health ethics. The required certainty (true positive and true negative) is guaranteed by the Ploner Model. Any program, either to examine all children by a doctor or moving parts of the school entry screening into the fourth year of life, require a continued critical evaluation and professional guidance. PMID- 28992659 TI - Monte Carlo Method Based QSAR Studies of Mer Kinase Inhibitors in Compliance with OECD Principles. AB - Monte Carlo method based QSAR studies for inhibitors of Mer kinase, a potential novel target for cancer treatment, has been carried out using balance of correlation technique. The data was divided into three random and dissimilar splits and hybrid optimal descriptors derived from SMILES and hydrogen filled graphs based notations were used for construction of QSAR models. The generated models have good fitting ability, robustness, generalizability and internal predictive ability. The external predictive ability has been tested using multiple criteria and described models exhibited good performance in all of these tests. The values of R2, Q2, R2test, Q2test, R2m and ?R2m for the best model are 0.9502, 0.9388, 0.9469, 0.9083, 0.7534 and 0.0894 respectively. Also, the structural characteristics responsible for enhancement and reduction of activity have been extracted. Further, the agreement with the OECD rules for QSAR model has been discussed. PMID- 28992660 TI - Alpha mangostin Inhibits Hepatic Stellate Cells Activation Through TGF-beta/Smad and Akt Signaling Pathways: An in vitro Study in LX2. AB - BACKGROUND: Alpha mangostin has been reported to have activity for the treatment of liver fibrosis in the rats. However, the mechanisms of action are poorly understood. This study was aimed to investigate the effect of alpha mangostin on hepatic stellate cells (HSC) activation and proliferation through TGF-beta/Smad and Akt signaling pathways. METHODS: Immortalized HSC, LX2 cells, were incubated with TGF-beta with or without alpha mangostin (5 or 10 MUM). Sorafenib 10 uM was used as positive control. LX2 viability was counted using trypan blue exclusion method. The effect of alpha mangostin on TGF-beta concentrations, and the expressions of proliferation and fibrogenic markers were evaluated. RESULTS: Alpha mangostin treatment resulted in a reduced proliferation of HSC, decreased Ki-67 and p-Akt expressions. These findings were followed with decreased concentrations of TGF-beta in the medium of cells treated with alpha mangostin, decreased expressions of COL1A1, TIMP1, PAI1, alpha-SMA, and p-Smad3 as fibrogenic markers. These effects were shown to be dose-dependent. CONCLUSIONS: Alpha mangostin inhibits hepatic stellate cells proliferation and activation through TGF-beta/Smad and Akt signaling pathways in dose dependent manner. PMID- 28992661 TI - The Anti-Inflammatory Potential of Mimosa caesalpiniifolia Following Experimental Colitis: Role of COX-2 and TNF-Alpha Expression. AB - The aim of this study was to evaluate the preventive and/or protective action of Mimosa caesalpiniifolia (M. caesalpiniifolia) following experimental colitis in rats. The rats were randomized into ten groups (n=10 per group), as follows: G1 - Sham group:; G2 - TNBS group; G3, G4 -colitis and treated with hydroalcoholic extract of M. caesalpiniifolia 250 mg/kg/day after and before/after inducing colitis, respectively; G5, G6 - colitis and treated with hydroalcoholic extract of M. caesalpiniifolia at 125 mg/kg/day after and before/after inducing colitis respectively; G7,G8 - colitis and treated with ethylacetate fraction of M. caesalpiniifolia at 50 mg/kg/day after and before/after inducing colitis, respectively; G9,G10 - colitis and treated with ethylacetate fraction of M. caesalpiniifolia at 50 mg/kg/day after and before/after inducing colitis, respectively. Rats treated with hydroalcoholic extract of M. caesalpiniifolia for both doses showed lower tissue damage in the distal colon. Ethylacetate fraction was effective at the highest dose only when administrated after inducing colitis. A downregulation of COX-2 was detected to rats suffering colitis and treated with M. caesalpiniifolia at high dose. On the other hand, TNF-alpha immunoexpression decreased in groups treated with M. caesalpiniifolia at low dose after inducing colitis. In summary, our results suggest that M. caesalpiniifolia attenuated the lesions of the colon, reduced inflammation, and modulates the expression of COX-2 and TNF-alpha during chronic colitis induced by TNBS when using for therapeutic purposes on a dose-dependent manner. PMID- 28992662 TI - Sample preparation method for the combined extraction of ethyl glucuronide and drugs of abuse in hair. AB - Often in hair analysis, a small hair sample is available while the analysis of a multitude of structurally diverse substances with different concentration ranges is demanded. The analysis of the different substances often requires different sample preparation methods, increasing the amount of required hair sample. When segmental hair analysis is necessary, the amount of hair sample needed is further increased. Therefore, the required sample amount for a full analysis can quickly exceed what is available. To combat this problem, a method for the combined hair sample preparation using a single extraction procedure for analysis of ethyl glucuronide with liquid chromatography-multistage fragmentation mass spectrometry/multiple reaction monitoring (LC-MS3 /MRM) and common drugs of abuse with LC-MRM was developed. The combined sample preparation is achieved by separating ethyl glucuronide from the drugs of abuse into separate extracts by fractionation in the solid-phase extraction step during sample clean-up. A full validation for all substances for the parameters selectivity, linearity, limit of detection, limit of quantification, accuracy, precision, matrix effects, and recovery was successfully completed. The following drugs of abuse were included in the method: Amphetamine; methamphetamine; 3,4-methylenedioxy-N methylamphetamine (MDMA); 3,4-methylenedioxyamphetamine (MDA); 3,4-methylenedioxy N-ethylamphetamine (MDE); morphine; 6-monoacetylmorphine; codeine; acetylcodeine; cocaine; benzoylecgonine; norcocaine; cocaethylene; methadone; 2-ethylidene-1,5 dimethyl-3,3-diphenylpyrrolidine (EDDP) and methylphenidate. In conclusion, as only 1 sample preparation is needed with 1 aliquot of hair, the presented sample preparation allows an optimal analysis of both ethyl glucuronide and of the drugs of abuse, even when the sample amount is a limiting factor. PMID- 28992663 TI - Metabolic analysis of the antidepressive effects of Yangxinshi Tablet in a vascular depression model in mice. AB - In recent years, vascular depression has become the focus of international attention. Yangxinshi Tablet (YXST) is usually used in cthe linic for the treatment of arrhythmia and heart failure, but we found that it also has antidepressive effects. The objective of the study was to identify biomarkers related to vascular depression in hippocampus and explore the antidepressive effects of YXST on the mouse model. Untargeted metabolomics based on UHPLC-Q TOF/MS was applied to identify significantly differential biomarkers between the model group and control group. Unsupervised principal component analysis (PCA) was used to scan the tendency of groups and partial least squares-discriminant analysis (PLS-DA) to distinguish between the vascular depressive mice and the sham. PCA stores showed clear differences in metabolism between the vascular depressive mice and sham groups. The PLS-DA model exhibited 38 metabolites as the biomarkers to distinguish the vascular depressive mice and the sham. Further, YXST significantly regulated 22 metabolites to normal levels. The results suggested that YXST has a comprehensive antidepressive effect on vascular depression via regulation of multiple metabolic pathways including amino acid, the tricarboxylic acid cycle and phosphoglyceride metabolisms. These findings provide insight into the pathophysiological mechanism underlying vascular depression and the mechanism of YXST. PMID- 28992664 TI - [Clinical Study on the Efficacy and Continuous Docetaxel Based Chemotherapy Treatment for Castration-Resistant Prostate Cancer]. AB - We report a retrospective study on the efficacy, adverse events and the factors for continuous docetaxel (DOC) therapy for patients with castration-resistant prostate cancer (CRPC). Between April 2007 and April 2015, 37 CRPC patients were treated with DOC therapy at Kanazawa Medical University Hospital. DOC was administered every 3 weeks at 70 mg/m2. Prostatic specific antigen (PSA) level, adverse events, cycles of DOC therapy, survival time and clinical passage were examined. Fifteen patients showed a decrease in PSA level of 50% or more, 9 patients showed less than 50% decrease in PSA level and 13 patients showed no decrease in PSA level. Adverse effect of grade 3 consisted of neutropenia in 29.7% and leukocytopenia in 10.8%. The median number of treatment cycles was 11.7 courses. The patients were divided into two groups ; the first group comprised of 26 patients who received short-term DOC therapy (<=10 cycles) and the second group comprised of 11 patients who received long-term DOC therapy (>=11 cycles). The 1-year survival rate was 59 and 100% for the short-term and long-term groups, respectively. Long-term treatment was related to pretreatment PSA nadir, time to progression of CRPC and serum lactate dehydrogenase level. PMID- 28992665 TI - [Clinical Study of Bladder Tamponade at Takeda Hospital]. AB - This retrospective study examined bladder tamponade in 58 patients (male, n=36 ; female, n=22 ; average age, 78.5 years old) at Takeda Hospital between 2006 and 2016. Twenty-four of the patients were prescribed anticoagulants, and 18 had an indwelling urethral catheter. The underlying diseases comprised of cystitis (male, n=7; female, n=19), iatrogenic lower urinary tract injury (male, n=13), bladder neoplasms (male, n=6 ; female, n=1), prostatic hemorrhage (male, n=7), renal cell carcinoma (male, n=1 ; female, n=1), and bladder stone (male, n=2 ; female, n=1). The ratios of cystitis and iatrogenic injury were significantly higher in females and males, respectively (p<0.0001). Elderly women in particular might be more in need of care due to a tendency towards bladder tamponade. Continuous bladder irrigation and transurethral coagulation were required more frequently for males than females. Radiation cystitis was not the cause of bladder tamponade in any of our patients, indicating that the incidence of bladder tamponade due to radiation cystitis has sharply decreased in Japan over the past 10 years. PMID- 28992666 TI - [An Increase in Cases of Bladder Tamponade Due to Cystitis Among Elderly Women and Clinical Background Factors]. AB - Bladder tamponade is thought to be caused mainly by bladder cancer or radiation cystitis. However, in women, it may often be caused by cystitis in clinical settings. This has not been noted in previous reports of bladder tamponade in Japan. Thus, we retrospectively analyzed the clinical features of 83 male and 41 female patients with bladder tamponade. Seventy-four patients were treated at Nishi-Kobe Medical Center between April 2005 and March 2015, and 50 were treated at Shizuoka City Shizuoka Hospital between November 2008 and March 2015. The patients'median age was 80 years. The cause of bladder tamponade was urological malignancies in 33 of the 83 male patients (40%), benign prostatic hyperplasia in 20 of the 83 male patients (24%), and cystitis in 33 of the 41 female patients (80%). Compared with the men, the women with bladder tamponade were significantly older and the proportion of patients with cerebrovascular disease, diabetes, and dementia was higher. In addition, more women were nursing home residents, with a higher rate of voiding with diapers and antithrombotic use than men. Causative strains of cystitis were diverse, and some were antibiotic resistant. Most of the cases of bladder tamponade in the women occurred in the elderly and were caused by cystitis. In an aging society, increases in the incidences of chronic, complicated cystitis due to impaired independent micturition, dysuria, and systemic diseases such as diabetes, and increased use of antithrombotic drugs may contribute to bladder tamponade in women. PMID- 28992667 TI - [A Case Report of Splenic Metastasis of Renal Cell Carcinoma]. AB - A 64-year-old female patient underwent radical left nephrectomy in 2005 after being diagnosed with renal cell carcinoma. The pathological diagnosis was pT2b pN0 M0 clear cell carcinoma. Three years postoperatively, metastatic recurrence in the para-aortic lymph node was noted, and the patient underwent retroperitoneal lymph node dissection in 2008. The pathological diagnosis was renal cell carcinoma (a combination of clear cell carcinoma and type 2 papillary cell carcinoma). Five years later, she exhibited splenic metastasis on computed tomography, but no other distant metastases were observed. She underwent splenectomy in 2013, and the pathological diagnosis was splenic metastasis of renal cell carcinoma (type 2 papillary cell carcinoma). Three months after the splenectomy, she developed multiple bone metastases but refused to undergo treatment with molecularly targeted drugs ; hence, she was transferred to palliative care services. Fourteen months after the splenectomy, she died of cancer. Most metastatic splenic tumors occur as part of multiple organ metastases in the terminal stage of renal cell carcinoma. If splenic metastasis of renal cell carcinoma is observed, further imaging studies should be performed, and splenectomy should only be considered if a definitive diagnosis of sporadic splenic metastasis is made. PMID- 28992668 TI - [Spontaneous Remission of Everolimus-Induced Interstitial Lung Disease in Metastatic Renal Cell Carcinoma : An Autopsy Case Report]. AB - Interstitial lung disease (ILD) is a common side effect of the mechanistic target of rapamycin inhibitor everolimus. Most cases of everolimus-induced ILD are mild and reversible. As per guidelines, even if Common Terminology Criteria for Adverse Events grade 1 or 2 everolimus-induced ILD occurs, either continuation of everolimus without dose reduction or readministration at a low dose is possible. However, the pathophysiology of everolimus-induced ILD is unknown. We present a case of everolimus-induced ILD with spontaneous remission during treatment in a patient with metastatic renal cell carcinoma. At autopsy, there was no evidence of remodeling or chronic inflammation in the lungs. Cryptogenic interstitual pneumonia and broncholitis obliterans with organizing pneumonia can be suspected as a pattern of mild everolimus-induced ILD. This case report provides evidence that everolimus-induced ILD is reversible fromthe pathological perspective. PMID- 28992669 TI - [A Case of Secondary Extramammary Paget's Disease Aroundthe Cutaneous Stoma after Radical Cystectomy]. AB - We present a case of secondary extramammary Paget's disease around the cutaneous ureterostomy stoma after radical cystectomy. An 85-year-old man with bacillus calmette-guerin refractory high-grade urothelial carcinoma underwent radical cystectomy and cutaneous ureterostomy construction. After right ureter cancer diagnosis, he underwent right nephroureterectomy 3 years after the cystectomy. He developed refractory dermatitis around the cutaneous stoma 1 year after the nephroureterectomy. Skin biopsy revealed secondary extramammary Paget's disease, cured by skin excision around the cutaneous stoma and skin grafting. Multiple urothelial carcinoma metastases were detected 6 months later ; he died of urothelial cancer 1 month later. PMID- 28992670 TI - [Segmental Testicular Infarction in a Patient with Epididymitis]. AB - Testicular nodules are occasionally palpable in patients with acute epididymitis. In these patients, we need to rule out testicular tumors. Advancement in imaging technology such as doppler ultrasound or magnetic resonance imaging (MRI) has enabled us to distinguish segmental testicular infarction from testicular tumor and refrain from orchiectomy. However, careful diagnosis is necessary and we should not hesitate to perform orchiectomy in case testicular tumor is not ruled out. Since segmental testicular infarction in the presence of epididymitis may occur, we should consider the disease in a case of hard testis in the presence of epididymitis. Herein we report a rare case of segmental testicular infarction after epididymitis, in which testicular tumor was difficult to rule out. PMID- 28992671 TI - Can Acute Stress Cause Esophageal Hypersensitivity in Healthy Individuals? PMID- 28992672 TI - The Clinical Implications of Overlap Between Constipation and Common Functional Gastrointestinal Disorders. PMID- 28992673 TI - Reflux Hypersensitivity: A New Functional Esophageal Disorder. AB - Reflux hypersensitivity, recently introduced by Rome IV as a new functional esophageal disorder, is currently considered as the presence of typical heartburn symptoms in patients with normal upper endoscopy and esophageal biopsies, normal esophageal pH test and with evidence of a close correlation between patients' heartburn and reflux events. Reflux hypersensitivity is very common and together with functional heartburn accounts for more than 90% of the heartburn patients who failed treatment with proton pump inhibitor twice daily. In addition, reflux hypersensitivity affects primarily young to middle aged women, commonly overlaps with another functional gastrointestinal disorders, and is often associated with some type of psychological comorbidity. Diagnosis is made by using endoscopy with esophageal biopsies, pH-impedance, and high-resolution esophageal manometry. Reflux hypersensitivity is primarily treated with esophageal neuromodulators, such as tricyclic anti-depressants and selective serotonin reuptake inhibitors among others. Surgical anti-reflux management may also play an important role in the treatment of reflux hypersensitivity. PMID- 28992674 TI - Is Helicobacter pylori Associated Functional Dyspepsia Correlated With Dysbiosis? AB - Background/Aims: To assess the long-term effect of Helicobacter pylori eradication on symptomatic improvement according to the type of antibiotic and the duration of treatment in H. pylori-associated functional dyspepsia. Methods: We searched Pubmed, Embase, CINAHL, and the Cochrane library databases for randomized controlled trials written in English and undertaken up to August 2016 that met our eligibility criteria. The search methodology used combinations of the following keywords: Helicobacter pylori OR H. pylori OR HP; dyspepsia OR functional dyspepsia OR non-ulcer dyspepsia; eradication OR cure OR treatment. The study outcome was the summary odds ratio (OR) for symptomatic improvement in H. pylori-associated functional dyspepsia with successful eradication therapy. Subgroup analyses were performed based on the type of antibiotic, and the duration of treatment, whether or not patients had symptoms of irritable bowel syndrome, and on race. Results: Sixteen randomized controlled trials met the inclusion criteria. The summary OR for symptomatic improvement in patients in our eradication group was 1.33 (95% confidence interval [CI], 1.16-1.54; P < 0.01). In a subgroup analysis on type of antibiotic, symptomatic improvement with metronidazole-containing regimen (OR, 1.87; 95% CI, 1.26-2.77) was better than treatment with clarithromycin (OR, 1.29; 95% CI, 1.11-1.50). H. pylori eradication therapy given for 10-14 days was the more effective for symptom improvement than 7-day therapy. When the studies excluding irritable bowel syndrome cases were analyzed, there were no therapeutic effects of H. pylori eradication on symptomatic improvement. Conclusions: In the clinical setting, the most effective H. pylori eradication regimen for functional dyspepsia to provide relief of symptoms is a metronidazole-based treatment regimen for at least 10 days. The explanation for this is that H. pylori-associated functional dyspepsia could be associated with dysbiosis. PMID- 28992675 TI - Relationship Between Salivary Pepsin Concentration and Esophageal Mucosal Integrity in Patients With Gastroesophageal Reflux Disease. AB - Background/Aims: Increased salivary pepsin could indicate an increase in gastro esophageal reflux, however, previous studies failed to demonstrate a correlation between salivary pepsin concentrations and 24-hour esophageal acid exposure. This study aims to detect the salivary pepsin and to evaluate the relationship between salivary pepsin concentrations and intercellular spaces (IS) in different gastroesophageal reflux disease phenotypes in patients. Methods: A total of 45 patients and 11 healthy volunteers were included in this study. All subjects underwent upper gastrointestinal endoscopy, 24-hour ambulatory multichannel impedance-pH (MII-pH) monitoring, and salivary sampling at 3-time points during the 24-hour MII-pH monitoring. IS were measured by transmission electron microscopy, and salivary pepsin concentrations were determined by enzyme-linked immunosorbent assay. Results: The IS measurements were greater in the esophagitis (EE), non-erosive reflux disease (NERD), and hypersensitive esophagus (HO) groups than in the functional heartburn (FH) and healthy volunteer groups, and significant differences were indicated. Patients with NERD and HO had higher average pepsin concentrations compared with FH patients. A weak correlation was determined between IS and salivary pepsin among patients with NERD (r = 0.669, P = 0.035). Conclusions: We confirmed the presence of a higher level of salivary pepsin in patients with NERD than in patients with FH. Salivary pepsin concentrations correlated with severity of mucosal integrity impairment in the NERD group. We suggest that in patients with NERD, low levels of salivary pepsin can help identify patients with FH, in addition the higher the pepsin concentration, the more likely the severity of dilated IS. PMID- 28992676 TI - Intravenous Corticotropin-releasing Hormone Administration Increases Esophageal Electrical Sensitivity in Healthy Individuals. AB - Background/Aims: When a person is experiencing stress, corticotropin-releasing hormone (CRH) can modulate gut physiologies, such as visceral sensation or gastrointestinal motility, and its intravenous administration mimics stress induced physiological changes. However, the influence of CRH on the esophagus is yet unknown. Accordingly, we investigated whether intravenous CRH administration increases esophageal sensitivity to electrical stimulation in healthy Japanese subjects. Methods: Twenty healthy subjects were recruited. We quantified the initial perception threshold (IPT) every 15 minutes after CRH injection. Venous blood was collected with a cannula, and both plasma adrenocorticotropic hormone (ACTH) and cortisol were measured at pre-stimulation, 0, 30, 60, 90, and 120 minutes. The results from each time point were compared against a baseline IPT obtained before electrical stimulation was initiated. Results: When compared to the baseline IPT value (16.9 +/- 4.5), CRH significantly decreased electrical threshold of the esophagus at 30, 45, 60, 75 minutes (14.1 +/- 4.2, 13.1 +/- 5.0, 12.1 +/- 5.7, 14.0 +/- 5.8 minutes, P < 0.01, respectively) after CRH injection, suggesting that CRH increased esophageal sensitivity to the electrical stimulus. CRH also significantly increased plasma ACTH levels at 30 minutes (50.3 +/- 17.7, P < 0.01), and cortisol levels at 30 minutes (22.0 +/- 6.7 minutes, P < 0.01) and 60 minutes (20.3 +/- 6.7 minutes, P < 0.01) after CRH injection, when compared to the pre-stimulation ACTH and cortisol values. Conclusion: Intravenous CRH administration increased esophageal electrical sensitivity in normal subjects, emphasizing the important role of stress in esophageal sensitivity. PMID- 28992677 TI - Nationwide Multicenter Study for Overlaps of Common Functional Gastrointestinal Disorders in Korean Patients With Constipation. AB - Background/Aims: In spite of increased concerns about the overlaps among the various functional gastrointestinal disorders (FGIDs), studies for the overlap between constipation and other common FGIDs are rare. Therefore, we investigated the patterns of overlaps between constipation and other common FGIDs. Methods: This study was designed as a prospective nationwide multi-center questionnaire study using Rome III questionnaires for functional dyspepsia (FD), irritable bowel syndrome (IBS), and functional constipation (FC), as well as various questionnaires about patients' information, degree of symptoms, and quality of life. For the evaluation of gastroesophageal reflux disease (GERD), GERD-Q was used. Results: From 19 centers, 759 patients with constipation were enrolled. The proportions of FC and IBS subtypes of constipation (IBS-C) were 59.4% and 40.6%, respectively. Among them, 492 (64.8%) showed no overlap. One hundred and thirty six patients (17.9%) presented overlapping GERD, and 80 patients (10.5%) presented overlapping FD. Fifty one (6.7%) of patients were overlapped by both GERD and FD. Coincidental herniated nucleus pulposus (HNP) (P = 0.026) or pulmonary diseases (P = 0.034), reduced fiber intake (P = 0.013), and laxative use (P < 0.001) independently affected the rate of overlaps. These overlapping conditions negatively affected the constipation-associated quality of life, general quality of life, and degree of constipation. Conclusions: The overlap of GERD or FD was common in patients with constipation. Coincidental HNP or pulmonary diseases, reduced fiber intake, and laxatives use were found to be independent associated factors for overlapping common FGIDs in Korean patients with constipation. PMID- 28992678 TI - Alterations of Food-specific Serum IgG4 Titers to Common Food Antigens in Patients With Irritable Bowel Syndrome. AB - Background/Aims: The role of dietary factors in the pathogenesis of irritable bowel syndrome (IBS) is still unclear. The aim of this study was to compare IgG4 levels to common food antigens between patients with IBS and healthy controls. Methods: Thirty-two patients diagnosed as IBS according to the Rome III criteria (12 diarrhea subgroup; 20 non-diarrhea subgroup) and 32 sex and age-matched healthy controls participated in the study. Serum IgG4 titers to 90 common foods were measured in each subject. The number of subjects with positivity defined as the cut-off value >= 0.7 U/mL was compared. Results: Patients with IBS had significantly higher IgG4 titers to wheat, leek and taro compared to those of controls. Serum IgG4 titers to ginger, cocoa, walnut, white radish, onion, and lettuce in IBS patients tended to be higher than controls. IgG4 titers to wheat, gluten and gliadin in the diarrhea subgroup, and lettuce, leek and taro in the non-diarrhea subgroup tended to be higher compared with controls. The number of subjects with positivity to apple, orange, lettuce, and leek was significantly higher in IBS patients than controls. The number of subjects with positivity to apple, orange, gluten, and gliadin in the diarrhea subgroup, and egg white, pineapple, soybean, lettuce, and leek in the non-diarrhea subgroup was significantly higher compared with controls. Conclusions: Serum IgG4 antibody levels to some common foods are abnormally elevated in IBS patients. The type of foods with abnormally elevated serum IgG4 titers in the diarrhea subgroup may be different from that in the non-diarrhea subgroup. PMID- 28992679 TI - A Rare Cause of Acute Colonic Pseudo-obstruction: Ogilvie's Syndrome Caused by Herpes Zoster. PMID- 28992680 TI - Application of computer-aided diagnosis in breast ultrasound interpretation: improvements in diagnostic performance according to reader experience. AB - PURPOSE: The purpose of this study was to evaluate the usefulness of applying computer-aided diagnosis (CAD) to breast ultrasound (US), depending on the operator's experience with breast imaging. METHODS: Between October 2015 and January 2016, two experienced readers obtained and analyzed the grayscale US images of 200 cases according to the Breast Imaging Reporting and Data System (BI RADS) lexicon and categories. They additionally applied CAD (S-Detect) to analyze the lesions and made a diagnostic decision subjectively, based on grayscale US with CAD. For the same cases, two inexperienced readers analyzed the grayscale US images using the BI-RADS lexicon and categories, added CAD, and came to a subjective diagnostic conclusion. We then compared the diagnostic performance depending on the operator's experience with breast imaging. RESULTS: The sensitivity values for the experienced readers, inexperienced readers, and CAD (for experienced and inexperienced readers) were 91.7%, 75%, 75%, and 66.7%, respectively. The specificity values for the experienced readers, inexperienced readers, and CAD (for experienced and inexperienced readers) were 76.6%, 71.8%, 78.2%, and 76.1%, respectively. When diagnoses were made subjectively in combination with CAD, the specificity significantly improved (76.6% to 80.3%) without a change in the sensitivity (91.7%) in the experienced readers. After subjective combination with CAD, the sensitivity and specificity improved in the inexperienced readers (75% to 83.3% and 71.8% to 77.1%). In addition, the area under the curve improved for both the experienced and inexperienced readers (0.84 to 0.86 and 0.73 to 0.8) after the addition of CAD. CONCLUSION: CAD is more useful for less experienced readers. Combining CAD with breast US led to improved specificity for both experienced and inexperienced readers. PMID- 28992681 TI - Ofatumumab Monoclonal Antibody Affinity Maturation Through in silico Modeling AB - Background: Ofatumumab, an anti-CD20 mAb, was approved in 2009 for the treatment of chronic lymphocytic leukemia. This mAb acts through immune-mediated mechanisms, in particular complement-dependent cytotoxicity and antibody dependent cellular cytotoxicity by natural killer cells as well as antibody dependent phagocytosis by macrophages. Apoptosis induction is another mechanism of this antibody. Computational docking is the method of predicting the conformation of an antibody-antigen from its separated elements. Validation of the designed antibodies is carried out by docking tools. Increased affinity enhances the biological action of the antibody, which in turn improves the therapeutic effects. Furthermore, the increased antibody affinity can reduce the therapeutic dose of the antibody, resulting in lower toxicity and handling cost. Methods: Considering the importance of this issue, using in silico analysis such as docking and molecular dynamics, we aimed to find the important amino acids of the Ofatumumab antibody and then replaced these amino acids with others to improve antibody-binding affinity. Finally, we examined the binding affinity of antibody variants to antigen. Results: Our findings showed that variant 3 mutations have improved the characteristics of antibody binding compared to normal Ofatumumab antibodies. Conclusion: In the present study, the designed anti CD20 antibodies showed to have potential for improved affinity compared to commercial Ofatumumab. PMID- 28992683 TI - Synchronous metastasis from double primary cancers in a single left supraclavicular lymph node. PMID- 28992682 TI - Nanocurcumin-Mediated Down-Regulation of Telomerase Via Stimulating TGFbeta1 Signaling Pathway in Hepatocellular Carcinoma Cells AB - Background: Curcumin, extracted from turmeric, represents enormous potential to serve as an anticancer agent. Telomerase is viewed as a prominent molecular target of curcumin, and Transforming growth factor-beta1 (TGFbeta1) has proven to be a major inhibitory signaling pathway for telomerase activity. In the current study, we aimed to explore suppressive effects of nanocurcumin on telomerase expression through TGFbeta1 pathway in a hepatocellular carcinoma cell line (Huh7). Methods: MTT assay was used to determine the effect of nonocurcumin on viability of Huh7 cells. RT-PCR was used to analyze the gene expression patterns. Results: MTT assay revealed that nanocurcumin acts in a dose- and time-dependent manner to diminish the cell viability. RT-PCR analysis indicated that nanocurcumin results in augmentation of TGFbeta1 72 hours post treatment and leads to the reduction of telomerase expression 48 and 72 hours post exposure. Also, up-regulation of Smad3 and E2F1 and down-regulation of Smad7 confirmed the effect of nanocurcumin on intermediate components of TGFbeta1 pathway. Furthermore, transfection of the proximal promoter of telomerase triggered a significant reduction in luciferase activity. Conclusion: The data from the present study lead us to develop a deeper understanding of the mechanisms underlying nanocurcumin-mediated regulation of telomerase expression, thereby presenting a new perspective to the landscape of using nanocurcumin as a cancer oriented therapeutic agent. PMID- 28992684 TI - Paricalcitol attenuates indoxyl sulfate-induced apoptosis through the inhibition of MAPK, Akt, and NF-kB activation in HK-2 cells. AB - Background/Aims: Indoxyl sulfate (IS) is a uremic toxin and an important causative factor in the progression of chronic kidney disease. Recently, paricalcitol (19-nor-1,25-dihydroxyvitamin D2) was shown to exhibit protective effects in kidney injury. Here, we investigated the effects of paricalcitol treatment on IS-induced renal tubular injury. Methods: The fluorescent dye 2',7' dichlorofluorescein diacetate was used to measure intracellular reactive oxygen species (ROS) following IS administration in human renal proximal tubular epithelial (HK-2) cells. The effects of IS on cell viability were determined using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays and levels of apoptosis-related proteins (Bcl-2-associated protein X [Bax] and B cell lymphoma 2 [Bcl-2]), nuclear factor-kappaB (NF- kappaB) p65, and phosphorylation of mitogen-activated protein kinase (MAPK) and protein kinase B (Akt) were determined by semiquantitative immunoblotting. The promoter activity of NF-kappaB was measured by luciferase assays and apoptosis was determined by f low cytometry of cells stained with f luorescein isothiocyanate-conjugated Annexin V protein. Results: IS treatment increased ROS production, decreased cell viability and induced apoptosis in HK-2 cells. IS treatment increased the expression of apoptosis-related protein Bax, decreased Bcl-2 expression, and activated phosphorylation of MAPK, NF-kappaB p65, and Akt. In contrast, paricalcitol treatment decreased Bax expression, increased Bcl-2 expression, and inhibited phosphorylation of MAPK, NF-kappaB p65, and Akt in HK-2 cells. NF kappaB promoter activity was increased following IS, administration and was counteracted by pretreatment with paricalcitol. Additionally, flow cytometry analysis revealed that IS-induced apoptosis was attenuated by paricalcitol treatment, which resulted in decreased numbers of fluorescein isothiocyanate conjugated Annexin V positive cells. Conclusions: Treatment with paricalcitol inhibited IS-induced apoptosis by regulating MAPK, NF-kappaB, and Akt signaling pathway in HK-2 cells. PMID- 28992685 TI - Is There a Change in Patient Preference for a Female Colonoscopist during the Last Decade in Korea? AB - BACKGROUND/AIMS: Patients may feel embarrassed during colonoscopy. Our study aimed to assess changes in patient preference, over the past decade, for the sex of their colonoscopist. METHODS: Prospective studies were performed at a single health center from July to September 2008, and from July to September 2016. Subjects included colonoscopy patients (2008: 354, 2016: 304) who were asked to complete a questionnaire before colonoscopy. RESULTS: In 2016, 69 patients (24.9%) expressed a sex preference, compared with 46 patients (14.6%) in 2008. By 2016, female patient preference for a female colonoscopist had significantly increased to 95% (odds ratio [OR], 2.678; 95% confidence interval [CI], 1.418- 5.057; P=0.002). In multivariate analysis, patient sex (OR, 4.404; P=0.000), patient age (OR, 0.977; 95% CI, 0.961-0.992; P=0.004), and year of procedure (OR, 1.674; 95% CI, 1.028-2.752) were statistically significant factors in sex preference. Between 2008 and 2016, female patients preferred a female colonoscopist because of embarrassment. Male patients also preferred a male colonoscopist, and the primary reason shifted from expertise to patient embarrassment (2008: 29%, 2016: 63%). CONCLUSIONS: Patients have an increased gender preference for the colonoscopist because of embarrassment. Taking this into account can increase patient satisfaction during colonoscopy. PMID- 28992687 TI - Through-Space Activation Can Override Substituent Effects in Electrophilic Aromatic Substitution. AB - Electrophilic aromatic substitution (EAS) represents one of the most important classes of reactions in all of chemistry. One of the "iron laws" of EAS is that an electron-rich aromatic ring will react more rapidly than an electron-poor ring with suitable electrophiles. In this report, we present unique examples of electron-deficient arenes instead undergoing preferential substitution in intramolecular competition with more electron-rich rings. These results were made possible by exploiting the heretofore unknown propensity of a hydrogen-bonding OH arene interaction to switch to the alternative HO-arene interaction in order to provide activation. In an extreme case, this through-space HO-arene activation is demonstrated to overcome the deactivating effect of a trifluoromethyl substituent, making an otherwise highly electron-deficient ring the site of exclusive reactivity in competition experiments. Additionally, the HO-arene activation promotes tetrabromination of an increasingly more electron-deficient arene before the unactivated "control" ring undergoes monobromination. It is our hope that these results will shed light on biological interactions as well as provide new strategies for the electrophilic substitution of aromatic rings. PMID- 28992686 TI - General, Auxiliary-Enabled Photoinduced Pd-Catalyzed Remote Desaturation of Aliphatic Alcohols. AB - A general, efficient, and site-selective visible light-induced Pd-catalyzed remote desaturation of aliphatic alcohols into valuable allylic, homoallylic, and bis-homoallylic alcohols has been developed. This transformation operates via a hybrid Pd-radical mechanism, which synergistically combines the favorable features of radical approaches, such as a facile remote C-H HAT step, with that of transition-metal-catalyzed chemistry (selective beta-hydrogen elimination step). This allows achieving superior degrees of regioselectivity and yields in the desaturation of alcohols compared to those obtained by the state-of-the-art desaturation methods. The HAT at unactivated C(sp3)-H sites is enabled by the easily installable/removable Si-auxiliaries. Formation of the key hybrid alkyl Pd radical intermediates is efficiently induced by visible light from alkyl iodides and Pd(0) complexes. Notably, this method requires no exogenous photosensitizers or external oxidants. PMID- 28992688 TI - Differential-Concentration Scanning Ion Conductance Microscopy. AB - Scanning ion conductance microscopy (SICM) is a nanopipette-based scanning probe microscopy technique that utilizes the ionic current flowing between an electrode inserted inside a nanopipette probe containing electrolyte solution and a second electrode placed in a bulk electrolyte bath, to provide information on a substrate of interest. For most applications to date, the composition and concentration of the electrolyte inside and outside the nanopipette is identical, but it is shown herein that it can be very beneficial to lift this restriction. In particular, an ionic concentration gradient at the end of the nanopipette, generates an ionic current with a greatly reduced electric field strength, with particular benefits for live cell imaging. This differential concentration mode of SICM (DeltaC-SICM) also enhances surface charge measurements and provides a new way to carry out reaction mapping measurements at surfaces using the tip for simultaneous delivery and sensing of the reaction rate. Comprehensive finite element method (FEM) modeling has been undertaken to enhance understanding of SICM as an electrochemical cell and to enable the interpretation and optimization of experiments. It is shown that electroosmotic flow (EOF) has much more influence on the nanopipette response in the DeltaC-SICM configuration compared to standard SICM modes. The general model presented advances previous treatments, and it provides a framework for quantitative SICM studies. PMID- 28992689 TI - Combining Explicit Quantum Solvent with a Polarizable Continuum Model. AB - A promising approach for accurately modeling both short-range and long-range solvation effects is to combine explicit quantum mechanical (QM) solvent with a classical polarizable continuum model (PCM), but the best PCM for these combined QM/classical calculations is relatively unexplored. We find that the choice of the solvation cavity is very important for obtaining physically correct results since unphysical double counting of solvation effects from both the QM solvent and the classical dielectric can occur with a poor choice of cavity. We investigate the dependence of electronic excitation energies on the definition of the PCM cavity and the self-consistent reaction field method, comparing results to large-scale explicit QM solvent calculations. For excitation energies, we identify the difference between the ground and excited state dipole moments as the key property determining the sensitivity to the PCM cavity. Using a linear response PCM approach combined with QM solvent, we show that excitation energies are best modeled by a solvent excluded surface or a scaled van der Waals surface. For the aqueous solutes studied here, we find that a scaled van der Waals surface defined by universal force field radii scaled by a factor of 1.5 gives reasonable excitation energies. When using an external iteration state-specific PCM approach, however, the excitation energies are most accurate with a larger PCM cavity, such as a solvent accessible surface. PMID- 28992690 TI - Atmospheric Chemistry of E- and Z-CF3CH?CHF (HFO-1234ze): OH Reaction Kinetics as a Function of Temperature and UV and IR Absorption Cross Sections. AB - We report here the rate coefficients for the OH reactions (kOH) with E-CF3CH?CHF and Z-CF3CH?CHF, potential substitutes of HFC-134a, as a function of temperature (263-358 K) and pressure (45-300 Torr) by pulsed laser photolysis coupled to laser-induced fluorescence techniques. For the E-isomer, the existing discrepancy among previous results on the T dependence of kOH needs to be elucidated. For the Z-isomer, this work constitutes the first absolute determination of kOH. No pressure dependence of kOH was observed, while kOH exhibits a non-Arrhenius behavior: kOH(E) = [Formula: see text] and kOH(Z) = [Formula: see text] cm3 molecule-1 s-1, where uncertainties are 2sigma. UV absorption cross sections, sigmalambda, are reported for the first time. From sigmalambda and considering a photolysis quantum yield of 1, an upper limit for the photolysis rate coefficients and lifetimes due to this process in the troposphere are estimated: 3 * 10-8 s-1 and >1 year for the E-isomer and 2 * 10-7 s-1 and >2 months for Z CF3CH?CHF, respectively. Under these conditions, the overall estimated tropospheric lifetimes are 15 days (for the E-isomer) and 8 days (for the Z isomer), the major degradation pathway being the OH reaction, with a contribution of the photolytic pathway of less than 3% (for E) and 13% (for Z). IR absorption cross sections were determined both experimentally (500-4000 cm-1) and theoretically (0-2000 cm-1). From the theoretical IR measurements, it is concluded that the contribution of the 0-500 cm-1 region to the total integrated cross sections is appreciable for the E-isomer (9%) but almost negligible for the Z-isomer (0.5%). Nevertheless, the impact on their radiative efficiency and global warming potential is negligible. PMID- 28992691 TI - A Ratiometric Fluorescent Probe for Monitoring Leucine Aminopeptidase in Living Cells and Zebrafish Model. AB - Leucine aminopeptidase (LAP) is an important cancer-related biomarker, which shows significant overexpression in malignant tumor cells like liver cancer. Developing an effective method to monitor LAP in tumor cells holds great potential for cancer diagnosis, treatment, and management. In this work, we report a novel BODIPY-based fluorescent probe (BODIPY-C-Leu) capable of monitoring LAP in vitro and in vivo in both ratiometric and turn-on model. BODIPY C-Leu contains an asymmetrical BODIPY dye for fluorescent signaling and a dipeptide (Cys-Leu) as the triggered moiety. Activation occurs by cleavage of the amide bond in dipeptides and subsequently an intramolecular S -> N conversion to convert sulfur-substituted BODIPY to amino-substituted BODIPY, resulting in a dramatic fluorescence variation to realize the detection of LAP. Furthermore, we have successfully employed BODIPY-C-Leu to monitor LAP activity in different cancer cells, indicating that HeLa cells have a higher level of LAP activity than A549 cells. Importantly, we demonstrated the capability of the probe for real time monitoring the drug-induced LAP level changes in zebrafish. PMID- 28992692 TI - Rare Hybrid Dimers with Anti-Acetylcholinesterase Activities from a Safflower (Carthamus tinctorius L.) Seed Oil Cake. AB - Safflower (Carthamus tinctorius) is commercially cultivated for vegetable oil extracted from the seeds. However, during the production process of seed oil, a large amount of the oil cake is thrown away or fermented as fertilizer to improve the homing rate of pigeons. Therefore, to solve the ecological problem and develop its new function, we investigated the chemical constituents of a safflower seed oil cake, and six new hybrid dimers, (+/-)-carthatins A-F (1-6, respectively), with a phenylpropanoid and a feruloylserotonin fused via a dihydrofuran ring, together with four known compounds, including sinapyl alcohol (7), coniferyl alcohol (8), serotobenine (9), and feruloylserotonin (10), were isolated. The extensive nuclear magnetic resonance spectra, combined with electronic circular dichroism analysis and chiral high-performance liquid chromatography, allowed the complete structural assignments of (+/-)-carthatins A F. Moreover, we evaluated their anti-acetylcholinesterase activities. Racemic carthatins A and B (1 and 2, respectively) showed anti-acetylcholinesterase effects with IC50 values of 17.96 and 66.83 MUM, respectively. To some extent, our findings provide a new scaffold of acetylcholinesterase inhibitors, which could be beneficial for developing therapeutic molecules for the treatment of Alzheimer's disease and supporting folk application of a safflower seed oil cake. PMID- 28992693 TI - Pinpoint Diagnostic Kit for Heat Stroke by Monitoring Lysosomal pH. AB - Heat stroke is one of the most serious causes of mortality. To prevent the situation, it is fundamental to research the mechanism of heat cytotoxicity. The preliminary results revealed that heat stroke and the change of lysosome acidity had some certain correlation. To further clarify their relationship, herein, we report a highly selective and sensitive fluorescence probe (NT1) for turn-on sensing of the pH value. NT2 was synthesized as control compound. Compared to NT2, NT1 showed accurate lysosome target ability. In addition, the suitable pKa value (5.67) allows NT1 to response to the changes of lysosomal pH values. Most importantly, NT1 could be used to study the correlation between the change of lysosomal pH and heat stroke. It was shown that the lysosomal pH value increasing with temperature during heat stroke. Thus, NT1 was an excellent candidate for research of the complex biological mechanism of heat stroke. PMID- 28992694 TI - SURPASS Low-Resolution Coarse-Grained Protein Modeling. AB - Coarse-grained modeling of biomolecules has a very important role in molecular biology. In this work we present a novel SURPASS (Single United Residue per Pre Averaged Secondary Structure fragment) model of proteins that can be an interesting alternative for existing coarse-grained models. The design of the model is unique and strongly supported by the statistical analysis of structural regularities characteristic for protein systems. Coarse-graining of protein chain structures assumes a single center of interactions per residue and accounts for preaveraged effects of four adjacent residue fragments. Knowledge-based statistical potentials encode complex interaction patterns of these fragments. Using the Replica Exchange Monte Carlo sampling scheme and a generic version of the SURPASS force field we performed test simulations of a representative set of single-domain globular proteins. The method samples a significant part of conformational space and reproduces protein structures, including native-like, with surprisingly good accuracy. Future extension of the SURPASS model on large biomacromolecular systems is briefly discussed. PMID- 28992695 TI - Formation, Aggregation, and Deposition Dynamics of NOM-Iron Colloids at Anoxic Oxic Interfaces. AB - The important role of natural organic matter (NOM)-Fe colloids in influencing contaminant transport, and this role can be influenced by the formation, aggregation, and particle deposition dynamics of NOM-Fe colloids. In this work, NOM-Fe colloids at different C/Fe ratios were prepared by mixing different concentrations of humic acid (HA) with 10 mg/L Fe(II) under anoxic conditions. The colloids were characterized by an array of techniques and their aggregation and deposition behaviors were examined under both anoxic and oxic conditions. The colloids are composed of HA-Fe(II) at anoxic conditions, while they are made up of HA-Fe(III) at oxic conditions until the C/Fe molar ratio exceeds 1.6. For C/Fe molar ratios above 1.6, the aggregation and deposition kinetics of HA-Fe(II) colloids under anoxic conditions are slower than those of HA-Fe(III) colloids under oxic conditions. Further, the aggregation of HA-Fe colloids under both anoxic and oxic conditions decreases with increasing C/Fe molar ratio from 1.6 to 23.3. This study highlights the importance of the redox transformation of Fe(II) to Fe(III) and the C/Fe ratio for the formation and stability of NOM-Fe colloids that occur in subsurface environments with anoxic-oxic interfaces. PMID- 28992697 TI - An Accurate Model for the Ion Current-Distance Behavior in Scanning Ion Conductance Microscopy Allows for Calibration of Pipet Tip Geometry and Tip Sample Distance. AB - The scanning ion conductance microscope (SICM) is an emerging tool for noncontact topography imaging and multiphysical investigation of soft samples in aqueous environments such as living cells. Despite the increasing popularity of SICM, several aspects of the imaging process are still unknown; for example, there is still no accurate description of the behavior of the ion current for a varying tip-sample distance. To predict this ion current-distance behavior, we provide a new numerical model based on finite element modeling. The model allows, for the first time, accurately determining the tip-sample distance during an SICM experiment. Furthermore, we present a nondestructive method for calibrating the pipet tip geometry by fitting the numerical model to the experimental ion current distance data and verify this method using pipets with opening radii between 30 and 300 nm. PMID- 28992696 TI - Hybrid All-Atom/Coarse-Grained Simulations of Proteins by Direct Coupling of CHARMM and PRIMO Force Fields. AB - Hybrid all-atom/coarse-grained (AA/CG) simulations of proteins offer a computationally efficient compromise where atomistic details are only applied to biologically relevant regions while benefiting from the speedup of treating the remaining parts of a given system at the CG level. The recently developed CG model, PRIMO, allows a direct coupling with an atomistic force field with no additional modifications or coupling terms and the ability to carry out dynamic simulations without any restraints on secondary or tertiary structures. A hybrid AA/CG scheme based on combining all-atom CHARMM and coarse-grained PRIMO representations was validated via molecular dynamics and replica exchange simulations of soluble and membrane proteins. The AA/CG scheme was also tested in the calculation of the free energy profile for the transition from the closed to the open state of adenylate kinase via umbrella sampling molecular dynamics method. The overall finding is that the AA/CG scheme generates dynamics and energetics that are qualitatively and quantitatively comparable to AA simulations while offering the computational advantages of coarse-graining. This model opens the door to challenging applications where high accuracy is required only in parts of large biomolecular complexes. PMID- 28992698 TI - Monitoring of Heparin Activity in Live Rats Using Metal-Organic Framework Nanosheets as Peroxidase Mimics. AB - Metal-organic framework (MOF) nanosheets are a class of two-dimensional (2D) porous and crystalline materials that hold promise for catalysis and biodetection. Although 2D MOF nanosheets have been utilized for in vitro assays, ways of engineering them into diagnostic tools for live animals are much less explored. In this work, a series of MOF nanosheets are successfully engineered into a highly sensitive and selective diagnostic platform for in vivo monitoring of heparin (Hep) activity. The iron-porphyrin derivative is selected as a ligand to synthesize a series of archetypical MOF nanosheets with intrinsic heme-like catalytic sites, mimicking peroxidase. Hep-specific AG73 peptides as recognition motifs are physically adsorbed onto MOF nanosheets, blocking active sites from nonspecific substrate-catalyst interaction. Because of the highly specific interaction between Hep and AG73, the activity of AG73-MOF nanosheets is restored upon the binding of Hep, but not Hep analogues and other endogenous biomolecules. Furthermore, by taking advantages of biocompatibility and diagnostic property enabled by AG73-MOF nanosheets, the elimination process of Hep in live rats is quantitatively monitored by coupling with microdialysis technology. This work expands the biomedical applications of 2D MOF nanomaterials and provides access to a promising in vivo diagnostic platform. PMID- 28992699 TI - Determination of Benzyl-hexadecyldimethylammonium 1,4-Bis(2 ethylhexyl)sulfosuccinate Vesicle Permeability by Using Square Wave Voltammetry and an Enzymatic Reaction. AB - This report describes the studies performed to determine the permeability coefficient value (P) of 1-naphthyl phosphate (1-NP) through the benzyl hexadecyldimethylammonium 1,4-bis(2-ethylhexyl)sulfosuccinate (AOT-BHD) vesicle bilayer. 1-NP was added in the external phase and must cross the bilayer of the vesicle to react with the encapsulated enzyme (alkaline phosphatase) to yield 1 naphtholate (NPh-), the product of the enzymatic hydrolysis. This product is electrochemically detected, at basic pH value, by a square wave voltammetry technique, which can be a good alternative over the spectroscopic one, to measure the vesicle solutions because scattering (due to its turbidity) does not make any influence in the electrochemical signal. The experimental data allow us to propose a mathematical model, and a value of P = (1.00 +/- 0.15) * 10-9 cm s-1 was obtained. Also, a value of P = (2.0 +/- 0.5) * 10-9 cm s-1 was found by using an independent technique, ultraviolet-visible spectroscopy, for comparison. It is evident that the P values obtained from both the techniques are comparable (within the experimental error of both techniques) under the same experimental conditions. This study constitutes the first report of the 1-NP permeability determination in this new vesicle. We want to highlight the importance of the introduction of a new method and the electrochemical response of the product generated through an enzymatic reaction that occurs in the inner aqueous phase of the vesicle, where the enzyme is placed. PMID- 28992700 TI - Flexibility vs Preorganization: Direct Comparison of Binding Kinetics for a Disordered Peptide and Its Exact Preorganized Analogues. AB - Many intrinsically disordered proteins, which are prevalent in nature, fold only upon binding their structured partner proteins. Such proteins have been hypothesized to have a kinetic advantage over their folded, preorganized analogues in binding their partner proteins. Here we determined the effects of ligand preorganization on the kon for a biomedically important system: an intrinsically disordered p53 peptide ligand and the MDM2 protein receptor. Based on direct simulations of binding pathways, computed kon values for fully disordered and preorganized p53 peptide analogues were within error of each other, indicating little if any kinetic advantage to being disordered or preorganized for binding the MDM2 protein. We also examined the effects of increasing the concentration of MDM2 on the extent to which its mechanism of binding to the p53 peptide is induced fit vs conformational selection. Results predict that the mechanism is solely induced fit if the unfolded state of the peptide is more stable than its folded state; otherwise, the mechanism shifts from being dominated by conformational selection at low MDM2 concentration to induced fit at high MDM2 concentration. Taken together, our results are relevant to any protein binding process that involves a disordered peptide of a similar length that forms a single alpha-helix upon binding a partner protein. Such disorder-to-helix transitions are common among protein interactions of disordered proteins and are therefore of fundamental biological interest. PMID- 28992701 TI - Exclusive Ni-N4 Sites Realize Near-Unity CO Selectivity for Electrochemical CO2 Reduction. AB - Electrochemical reduction of carbon dioxide (CO2) to value-added carbon products is a promising approach to reduce CO2 levels and mitigate the energy crisis. However, poor product selectivity is still a major obstacle to the development of CO2 reduction. Here we demonstrate exclusive Ni-N4 sites through a topo-chemical transformation strategy, bringing unprecedentedly high activity and selectivity for CO2 reduction. Topo-chemical transformation by carbon layer coating successfully ensures preservation of the Ni-N4 structure to a maximum extent and avoids the agglomeration of Ni atoms to particles, providing abundant active sites for the catalytic reaction. The Ni-N4 structure exhibits excellent activity for electrochemical reduction of CO2 with particularly high selectivity, achieving high faradaic efficiency over 90% for CO in the potential range from 0.5 to -0.9 V and gives a maximum faradaic efficiency of 99% at -0.81 V with a current density of 28.6 mA cm-2. We anticipate exclusive catalytic sites will shed new light on the design of high-efficiency electrocatalysts for CO2 reduction. PMID- 28992702 TI - Open Boundary Simulations of Proteins and Their Hydration Shells by Hamiltonian Adaptive Resolution Scheme. AB - The recently proposed Hamiltonian adaptive resolution scheme (H-AdResS) allows the performance of molecular simulations in an open boundary framework. It allows changing, on the fly, the resolution of specific subsets of molecules (usually the solvent), which are free to diffuse between the atomistic region and the coarse-grained reservoir. So far, the method has been successfully applied to pure liquids. Coupling the H-AdResS methodology to hybrid models of proteins, such as the molecular mechanics/coarse-grained (MM/CG) scheme, is a promising approach for rigorous calculations of ligand binding free energies in low resolution protein models. Toward this goal, here we apply for the first time H AdResS to two atomistic proteins in dual-resolution solvent, proving its ability to reproduce structural and dynamic properties of both the proteins and the solvent, as obtained from atomistic simulations. PMID- 28992703 TI - Influence of Frozen Residues on the Exploration of the PES of Enzyme Reaction Mechanisms. AB - In this work, we studied one of the very widely used approximations in the prediction of an enzyme reaction mechanism with computational methods, that is, fixing residues outside a given radius surrounding the active site. This avoids the unfolding of truncated models during MD calculations, avoids the expansion of the active site in cluster model calculations (albeit here only specific atoms are frozen), and prevents drifting between local minima when adiabatic mapping with large QM/MM models is used. To test this, we have used the first step of the reaction catalyzed by HIV-1 protease, as the detrimental effects of this approximation are expected to be large here. We calculated the PES with shells of frozen residues of different radii. Models with free regions under a 6.00 A radius showed signs of being overconstrained. The QM/MM energy barrier for the remaining models was only slightly sensitive to this approximation (average of 0.8 kcal.mol-1, maximum of 1.6 kcal.mol-1). The influence over the energy of reaction was almost negligible. This widely used approximation seems safe and robust. The resulting error is on average below 1.6 kcal.mol-1, which is small when compared with others deriving from, for example, the choice of the density functional or semiempirical MO/SCC-DFTB method, the basis set used, or even the lack of sampling or incomplete sampling. PMID- 28992704 TI - Mutants of the Flavoprotein iLOV as Prospective Red-Shifted Fluorescent Markers. AB - We report on novel variants of the flavin-based fluorescent protein iLOV with absorption and emission optical bands shifted to the longer wavelengths relative to their precursor. First attempts (J. Phys. Chem. B 2015, 119, 5176; 2016, 120, 3344) to improve spectral properties of iLOV, a fluorescent marker in living cells, showed that single point mutation Q489K could lead to a promising variant, but its realization was not successful due to unfavorable conformation of the flexible lysine side chain pointing away from the chromophore. The results of molecular simulations presented in this work evidence that location of the charged lysine residue near the chromophore isoalloxazine ring can be fixed by introducing additional mutations in iLOV. Several suggested protein variants are characterized by using classical and QM/MM molecular dynamics simulations followed by optimization of structures in the ground and excited states. Transition energies between the S0 and S1 states are computed by using the advanced quantum chemical methods TD-DFT, SOS-CIS(D), and XMCQDPT2. According to our simulations, the chromophore-containing pockets for the red-shifted iLOV variants containing lysine either at position 392 (V392K/F410V/A426S) or at position 489 (Q489K/L470T) should be stable and exhibit absorption and emission bands red-shifted by 40-50 nm relative to iLOV. PMID- 28992705 TI - Importance of Scaffold Flexibility/Rigidity in the Design and Directed Evolution of Artificial Metallo-beta-lactamases. AB - We describe the design and evolution of catalytic hydrolase activity on a supramolecular protein scaffold, Zn4:C96RIDC14, which was constructed from cytochrome cb562 building blocks via a metal-templating strategy. Previously, we reported that Zn4:C96RIDC14 could be tailored with tripodal (His/His/Glu), unsaturated Zn coordination motifs in its interfaces to generate a variant termed Zn8:A104AB34, which in turn displayed catalytic activity for the hydrolysis of activated esters and beta-lactam antibiotics. Zn8:A104AB34 was subsequently subjected to directed evolution via an in vivo selection strategy, leading to a variant Zn8:A104/G57AB34 which displayed enzyme-like Michaelis-Menten behavior for ampicillin hydrolysis. A criterion for the evolutionary utility or designability of a new protein structure is its ability to accommodate different active sites. With this in mind, we examined whether Zn4:C96RIDC14 could be tailored with alternative Zn coordination sites that could similarly display evolvable catalytic activities. We report here a detailed structural and functional characterization of new variant Zn8:AB54, which houses similar, unsaturated Zn coordination sites to those in Zn8:A104/G57AB34, but in completely different microenvironments. Zn8:AB54 displays Michaelis-Menten behavior for ampicillin hydrolysis without any optimization. Yet, the subsequent directed evolution of Zn8:AB54 revealed limited catalytic improvement, which we ascribed to the local protein rigidity surrounding the Zn centers and the lack of evolvable loop structures nearby. The relaxation of local rigidity via the elimination of adjacent disulfide linkages led to a considerable structural transformation with a concomitant improvement in beta-lactamase activity. Our findings reaffirm previous observations that the delicate balance between protein flexibility and stability is crucial for enzyme design and evolution. PMID- 28992706 TI - Binding Free Energies of Host-Guest Systems by Nonequilibrium Alchemical Simulations with Constrained Dynamics: Theoretical Framework. AB - The fast-switching decoupling method is a powerful nonequilibrium technique to compute absolute binding free energies of ligand-receptor complexes (Sandberg et al., J. Chem. Theory Comput. 2014, 11, 423-435). Inspired by the theory of noncovalent binding association of Gilson and co-workers (Biophys. J. 1997, 72, 1047-1069), we develop two approaches, termed binded-domain and single-point alchemical-path schemes (BiD-AP and SiP-AP), based on the possibility of performing alchemical trajectories during which the ligand is constrained to fixed positions relative to the receptor. The BiD-AP scheme exploits a recent generalization of nonequilibrium work theorems to estimate the free energy difference between the coupled and uncoupled states of the ligand-receptor complex. With respect to the fast-switching decoupling method without constraints, BiD-AP prevents the ligand from leaving the binding site, but still requires an estimate of the positional binding-site volume, which may not be a simple task. On the other side, the SiP-AP scheme allows avoidance of the calculation of the binding-site volume by introducing an additional equilibrium simulation of ligand and receptor in the bound state. In the companion article (DOI: 10.1021/acs.jctc.7b00595), we show that the extra computational effort required by SiP-AP leads to a significant improvement of accuracy in the free energy estimates. PMID- 28992707 TI - [Overgrowth in children and in adults: novel clinical view, novel genes, novel phenotypes]. AB - Novel genetic findings allow to more reliably elucidate the aetiology and pathogenesis of overgrowth syndromes in children and in adults. The relatively prevalent overgrowth syndromes in foetuses and neonates include Beckwith Wiedemann (BWS) and Sotos syndromes; in addition, several rare conditions may occur e.g. Simpson-Golabi-Behmel and Weaver syndromes. These syndromes are not connected with overproduction of growth hormone. Their carriers are at risk of hypoglycaemia (in BWS), of congenital malformations and of childhood tumours. Targeted oncologic screening may improve the outcomes. Despite rapid growth even postnatally, the final height is mostly normal. In childhood and adolescence, the increased growth velocity results from hormonal overproduction - of precocious production of sexual hormones, hyperthyroidism, or of growth hormone overproduction due to pituitary adenoma that may lead to gigantism or acrogigantism and may be familiar (familiar isolated pituitary adenoma; FIPA). In 15-25 % of affected families, FIPA is caused by autosomal dominantly inherited mutations of AIP gene encoding a tumour suppressor protein named AIP (aryl hydrocarbon receptor-interacting protein). X-linked acrogigantism (X-LAG) is due to GPR101 gene mutations or microduplications of Xq26 chromosomal region. GPR101 encodes G-protein coupled receptor with unknown ligand. X-LAG is associated with recurrent and highly-penetrant pituitary macroadenomas. Mutations of additional at least 10 genes may lead to pituitary tumour with growth hormone overproduction. Gigantism in adults results from untreated or insufficiently treated pituitary adenoma in childhood. Some of the well-known current or past giants were found to carry pathogenic genetic variants of GPR101 or AIP. PMID- 28992708 TI - [Management of patients with thyroid nodules: American Thyroid Association guidelines in the setting of Czech Republic]. AB - Thyroid nodules are common finding. Most of them are of benign origin without thyroid dysfunction. Diagnosis is based on evaluation of thyroid function by assessment of serum thyroid stimulating hormone, and ultrasound for the purpose to identify the nodules which should be referred to fine needle aspiration biopsy (FNAB). The nodule size, ultrasound pattern and clinical risk factors should be considered before the FNAB is performed. The FNAB results should be categorized based on the risk of malignancy to improving a standardization of the patients management and minimizing number of false negative and false positive FNAB results. The most appropriate categorizing system seems to be Bethesda classification, although it is not completely optimal mainly because of controversial Bethesda III category. PMID- 28992709 TI - [Adrenal insufficiency]. AB - Adrenal insufficiency (AI) is an endocrine disorder characterized by a decrease in cortisol secretion in adrenal cortex. AI even if properly diagnosed and treated is connected with a significant increase in morbidity and mortality and a decrease in quality of life. This review article summarizes basics of clinical presentation, diagnosis, differential diagnostic and treatment necessary for physicians of nearly all specialties and for improvement of the prognosis of patient suffering from AI. PMID- 28992710 TI - [Male hypogonadism and its treatment]. AB - Male hypogonadism can be of various etiology and that reflects its clinical manifestation, diagnostics and treatment. Male hypogonadism leads not only to decreased fertility, but influences the cardiovascular system, mood changes, bone fragility, lipids and other metabolic functions. Diagnosis of hypogonadism can be cumbersome, as well as the choice of optimal hormonal supplementation. The aim of this article is to summarize the basics from symptoms, diagnosis and treatment of male hypogonadism. PMID- 28992711 TI - [Treatment of pituitary adenomas]. AB - Pituitary adenomas are the most common tumours of the sellar region. A combination of neurosurgery, radiation and pharmacological approaches are applied for the treatment of pituitary adenomas. In certain cases, patient observation is another option. Neurosurgery is the first-choice treatment for acromegaly, Cushing's disease and TSH secreting adenomas. Leksell gamma knife irradiation is used in the treatment of tumour residues. Until the effect of the irradiation is evident, pharmacological treatment must be administered. Large and/or growing non functioning pituitary adenomas are operated. Irradiation is possible if there is sufficient distance between the margin of the adenoma and the optic pathway. The primary therapy for prolactinomas is pharmacological treatment with dopamine agonists. Multidisciplinary collaboration among endocrinologists, neurosurgeons and radiosurgeons is necessary in the treatment of pituitary adenomas. PMID- 28992712 TI - [Biologic aspects of ADHD and conduct disorders in childhood and adolescence, selected preventive aspects]. AB - Next to environmental factors and problems with interpersonal interaction in family represent developmental findings the basic of understanding these disorders (ADHD, conduct disorders, obsessive-compulsive disorders, tic disorders etc.). Knowledges of neurodevelopment disorders represent new possibilities of prevention and treatment. PMID- 28992714 TI - A review of the availability and cost effectiveness of chronic obstructive pulmonary disease (COPD) management interventions in rural Australia and New Zealand. AB - INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a chronic, progressive disease, which consumes a significant proportion of the Australian and New Zealand healthcare budget. Studies have shown that people living with COPD outside of urban areas have higher rates of hospitalisations. Two international reviews have demonstrated reduced hospital admissions and length of stay in people with COPD who participate in an integrated disease management program. However, most studies included in these reviews are in urban settings. The purpose of this review is to explore the type and cost-effectiveness of COPD management interventions located in rural or remote settings of Australia and New Zealand in order to inform planning and ongoing service development in the authors' local health district. METHOD: Six databases and Google scholar were searched to find literature relating to the availability and cost-effectiveness of non-pharmaceutical interventions for the management of COPD in rural and remote areas of Australia and New Zealand. RESULTS: Two studies were found that met the inclusion criteria. Both studies had small sample sizes, were single intervention studies and showed a positive influence on variables such as number of hospital admissions and length of stay at 12 months post-intervention. However, because of the limited number of studies and the lack of homogeneity of interventions, no conclusions regarding availability and cost-effectiveness of COPD interventions in rural and remote areas of Australia and New Zealand could be drawn. CONCLUSIONS: Limited literature exists to inform planning and development of services for people with COPD living in rural and remote areas of Australia and New Zealand. Approximately 50% of pulmonary rehabilitation programs are situated in rural and remote locations in Australia and New Zealand. Outcomes from existing programs need to be reported in a consistent and coordinated manner to allow evaluation of health resource utilisation. PMID- 28992713 TI - Household resources as determinants of child mortality in Ghana. AB - INTRODUCTION: Although the association between child mortality and socioeconomic status is well established, the role of household assets as predictors of child mortality, over and above other measures of socioeconomic status, is not well studied in developing nations. This study investigated the contribution of several household resources to child mortality, beyond the influence of maternal education as a measure of socioeconomic status. METHODS: This secondary analysis used data from the 2007 Ghana Maternal Health Survey to explore the relationship of child mortality to household resources. The analysis of 7183 parous women aged 15-45 years examined household resources for their association with maternal reports of any child's death for children aged less than 5 years using a survey weighted logistic regression model while controlling for sociodemographic and health covariates. RESULTS: The overall household resources index was significantly associated with the death of one or more child in the entire sample (adjusted odd ratios (OR)=0.95; 95% confidence interval (CI): 0.92, 0.98]. In stratified analysis, this finding held for women living in rural but not in urban areas. Having a refrigerator at the time of interview was associated with lower odds of reporting child mortality (OR=0.63; 95%CI: 0.48, 0.83). Having a kerosene lantern (OR=1.40; 95%CI: 1.06, 1.85) or flush toilet (OR=1.84; 95%CI: 1.23, 2.75) was associated with higher odds of reporting child mortality. Adjusted regression models showed only possession of a refrigerator retained significance. CONCLUSIONS: Possession of a refrigerator may play a role in child mortality. This finding may reflect unmeasured socioeconomic status or the importance of access to refrigeration in preventing diarrheal disease or other proximal causes of child mortality in sub-Saharan Africa. PMID- 28992715 TI - "My Future is Now": A Qualitative Study of Persons Living With Advanced Cancer. AB - OBJECTIVES: Advance care planning (ACP) enables individuals to deliberate about future preferences for care based upon their values and beliefs about what is important in life. For many patients with advanced cancer, however, these critical conversations do not occur. A growing body of literature has examined the end-of-life wishes of seriously ill patients. Few studies have explored what is important to persons as they live with advanced cancer. The aim of the current study was to address this gap and to understand how clinicians can support patients' efforts to live in the present and plan for the future. METHODS: Transcriptions of interviews conducted with 36 patients diagnosed with advanced cancer were analyzed using immersion-crystallization, a qualitative research technique. RESULTS: Four overarching themes were identified: (I) living in the face of death, (II) who I am, (III) my experience of cancer, and (IV) impact of my illness on others. Twelve subthemes are also reported. SIGNIFICANCE OF RESULTS: These findings have significant implications for clinicians as they partner with patients to plan for the future. Our data suggest that clinicians consider the following 4 prompts: (1) "What is important to you now, knowing that you will die sooner than you want or expected?" (2) "Tell me about yourself." (3) "Tell me in your own words about your experience with cancer care and treatment." (4) "What impact has your illness had on others?" In honoring patients' lived experiences, we may establish the mutual understanding necessary to providing high-quality care that supports patients' priorities for life. PMID- 28992716 TI - The short-term effect of smoking on fetal ECG. AB - BACKGROUND: The number of women who smoke during pregnancy is significant even today. The harmful effects of smoking during pregnancy are well known but there are no data on the effects of smoking on fetal electrocardiography (ECG). The lack of data is in connection with the difficulties of recording fetal ECG through the maternal abdomen. METHOD: Third trimester pregnant women who were not able to give up the harmful passion of smoking despite repeated attempts of persuasion were recruited in the study on voluntary basis. The fetal ECG was recorded non-invasively through the maternal abdomen before, during and after smoking, then the data were processed offline. The electrophysiological measurements were performed by a self developed ECG device, which allowed the examination of the morphological differences in "true-to-form" fetal ECG in addition to studying the variability of fetal heart rate. The study involved nine pregnant women. The observed changes are presented through case studies of those pregnant women who showed the most significant anomalies. RESULTS: Compared with the resting state fetal heart rate was increased during smoking. The short-term variability of fetal heart rate was narrowed, while the mother's heart rate did not change significantly - which was an indication of direct fetal stress. No explicit ischemic signs were detected in fetal ECG during smoking, however, in the increasing period of the fetal heart rate, the T wave morphology changed slightly, then it returned to normal. CONCLUSIONS: Demonstrable by the electrophysiological methods, smoking has a direct effect on fetal cardiac function. The fetal heart rate variability shows a pattern during smoking which is a typical sign of stress conditions among adults. The results may have educational consequences as well. Understanding those, hopefully will help pregnant women give up this harmful addiction. PMID- 28992717 TI - Accuracy of transcutaneous bilirubinometry in the preterm infants: a comprehensive meta-analysis. AB - BACKGROUND: Transcutaneous bilirubin (TcB) measurement is widely used in term babies. But its effectiveness till debated in preterm infants. So, our objective was to pool data to see the accuracy of transcutaneous bilirubinometry in preterm infants. METHOD: MEDLINE, Embase, Cochrane Library database were searched from 2000 to July 2017. The included studies had compared TcB with total serum bilirubin (TSB) in preterm infants before phototherapy and data were presented as correlation coefficients. Data were extracted by two reviewers and checked for accuracy by the third reviewer. The risk bias assessments were done by an assessment quality assessment of diagnostic accuracy studies tool. Pooled correlation coefficient assed after Fisher's z transformation and then converted to r. RESULTS: We included 28 studies; all those studies reported results as correlation coefficients. In combination of both sternal and forehead site measurement, our pooled estimates of r = 0.82 (95% CI: 0.78-0.85) in random effect and r = 0.803 (95% CI: 0.78-0.81) in fixed effect model. For separate sites of measurement of TcB pooled r for forehead and sternum were comparable, r = 0.82 (95% CI: 0.78-0.85), and pooled correlation coefficient for the two devices JM103 and Bilicheck the estimated pooled r were also comparable (Pooled r = 0.83). CONCLUSION: Our study found that TcB measurement is well related with TSB values and can represent a reliable method for evaluating preterm infants with possible hyperbilirubinemia. Our findings support the use of investigated devices at both forehead and sternum sites in preterm infants. PMID- 28992718 TI - Advanced maternal age and risk of non-chromosomal anomalies: data from a tertiary referral hospital in Turkey. AB - PURPOSE: The purpose of this study is to determine if there is a relationship between non-chromosomal fetal anomalies of various organ systems and advanced maternal age. MATERIALS AND METHOD: This study was conducted in 387 women aged 20 53 years who underwent fetal karyotype testing due to positive prenatal test results or advanced maternal age at the Kanuni Sultan Suleyman Training and Research Hospital between September 2011 and March 2015. Fetuses with chromosomal anomalies were excluded from the study. The relationship between non-chromosomal anomalies and maternal age of women aged <35 or >=35 years was studied. RESULTS: More than 80% (81.7%) of non-chromosomal anomalies were detected in patients aged <35 years, and 18.3% were found in those >=35 years. There were no statistically significant differences found between the incidence of non-chromosomal anomalies in women aged over 35 years and those under 35 years. When congenital major anomalies were evaluated with respect to various organ systems, the risk of musculo-skeletal system anomalies decreased with advancing maternal age. However, there was no statistically significant difference between the <35 and >=35-year age groups in the incidence of central nervous system, craniofacial, cardiac, gastrointestinal system, urogenital, respiratory, and limb anomalies. CONCLUSION: The incidence of non-chromosomal anomalies does not increase in fetuses of pregnant women aged over 35 years, in contrast to chromosomal anomalies. PMID- 28992719 TI - Incidence of congenital diaphragmatic hernia in Olmsted County, Minnesota: a population-based study. AB - OBJECTIVE: The rate of congenital diaphragmatic hernia (CDH) varies, but most reports estimate the incidence to be less than three per 10,000 births. Our objective was to document the incidence of CDH in a geographically well-defined population using available resources for highly accurate incident case ascertainment. METHODS: We ascertained CDH cases in Olmsted County, Minnesota, United States of America, from 1981 through 2014 using resources of the Rochester Epidemiology Project. Overall and sex-specific incidence rates were calculated, and hospital survival was assessed. RESULTS: A total of 26 incident CDH cases were identified; the overall incidence of 3.6 (95% CI, 2.2-5.0) per 10,000 did not differ significantly over the 34-year study period (p = .28). The estimated incidence was 4.3 (95% CI, 2.2-6.5) for male infants and 2.9 (95% CI, 1.1-4.6) for female infants. The percentage of cases diagnosed prenatally was 33% from 1981 through 2000 and 50% from 2001 through 2014. The rate of survival to discharge in the two periods was 50% and 88%. CONCLUSION: The incidence of CDH in Olmsted County exceeds the majority of published rates, which most likely can be attributed to our comprehensive case ascertainment. PMID- 28992720 TI - Accuracy and Time Delay of Glucose Measurements of Continuous Glucose Monitoring and Bedside Artificial Pancreas During Hyperglycemic and Euglycemic Hyperinsulinemic Glucose Clamp Study. AB - BACKGROUND: Glucose values of continuous glucose monitoring (CGM) have time delays compared with plasma glucose (PG) values. The artificial pancreas (STG-55, Nikkiso, Japan) (AP), which measures venous blood glucose directly, also has a time delay because of the long tubing lines from sampling vessel to the glucose sensor. We investigate accuracy and time delay of CGM and AP in comparison with PG values during 2-step glucose clamp study. METHODS: Seven patients with type 2 diabetes and 2 healthy volunteers were included in this study. CGM (Enlite sensor, Medtronic, Northridge, CA, USA) was attached on the day before the experiment. Hyperglycemic (200 mg/dL) clamp was performed for 90 minutes, followed by euglycemic (100 mg/dL) hyperinsulinemic (100 MUU/mL) clamp for 90-120 minutes using AP. CGM sensor glucose was calibrated just before and after the clamp study. AP and CGM values were compared with PG values. RESULTS: AP values were significantly lower than PG values at 5, 30 minute during hyperglycemic clamp. In comparison, CGM value at 0 minute was significantly higher, and its following values were almost significantly lower than PG values. The time delay of AP and CGM values to reach maximum glucose levels were 5.0 +/- 22.3 (NS) and 28.6 +/- 32.5 ( P < .05) min, respectively. Mean absolute rate difference of CGM was significantly higher than AP (24.0 +/- 7.6 vs 15.3 +/- 4.6, P < .05) during glucose rising period (0-45 min); however, there were no significant differences during other periods. CONCLUSIONS: Both CGM and AP failed to follow plasma glucose values during nonphysiologically rapid glucose rising, but indicated accurate values during physiological glucose change. PMID- 28992721 TI - Correlation of Hallux Rigidus Grade With Motion, VAS Pain, Intraoperative Cartilage Loss, and Treatment Success for First MTP Joint Arthrodesis and Synthetic Cartilage Implant. AB - BACKGROUND: Grading systems are used to assess severity of any condition and as an aid in guiding treatment. This study examined the relationship of baseline motion, pain, and observed intraoperative cartilage loss with hallux rigidus grade. METHODS: A prospective, randomized study examining outcomes of arthrodesis compared to synthetic cartilage implant was performed. Patients underwent preoperative clinical examination, radiographic assessment, hallux rigidus grade assignment, and intraoperative assessment of cartilage loss. Visual analog scale (VAS) score for pain was obtained preoperatively and at 24 months. Correlation was made between active peak dorsiflexion, VAS pain, cartilage loss, and hallux rigidus grade. Fisher's exact test was used to assess grade impact on clinical success ( P < .05). RESULTS: In 202 patients, 59 (29%), 110 (55%), and 33 (16%) were classified as Coughlin grades 2, 3, and 4, respectively. There was no correlation between grade and active peak dorsiflexion (-0.069, P = .327) or VAS pain (-0.078, P = .271). Rank correlations between grade and cartilage loss were significant, but correlations were small. When stratified by grade, composite success rates between the 2 treatments were nearly identical. CONCLUSIONS: Irrespective of the grade, positive outcomes were demonstrated for both fusion and synthetic cartilage implant. Clinical symptoms and signs should be used to guide treatment, rather than a grade consisting of radiographic, symptoms, and range of motion factors. LEVEL OF EVIDENCE: Level II, randomized clinical trial. PMID- 28992722 TI - The treatment of pseudoaneurysms with flow diverters after malignant otitis externa. AB - Background We report a case of bilateral malignant otitis externa complicated with bilateral petrous internal carotid artery pseudoaneurysms and their successful treatment with a flow diverter. Case report A 68-year-old woman with serious complications of type II diabetes mellitus had malignant otitis externa on the right side. She was treated with combined antibiotic therapy and underwent mastoidectomy for mastoiditis. She presented at our hospital with acute hemorrhage from the right external auditory canal. The emergency computed tomography (CT) angiography revealed a multiobulated pseudoaneurysm at the petrous segment of the right internal carotid artery. The pseudoaneurysm was treated with a 5 * 40-mm Surpass flow diverter. Three months later, she developed a malignant external otitis on the left side. As the infection progressed, a left sided mastoiditis, a brain abscess, and a pseudoaneurysm at the petrous segment of the left internal carotid artery developed. The pseudoaneurysm caused bleeding from the left ear, and was treated with a 5 * 50-mm Surpass flow diverter. No recurrent bleeding was observed. Four months later, a follow-up angiography showed complete occlusion of the pseudoaneurysm on the left side, but a residual aneurysm could be detected on the right side. One year after the first intervention, the follow-up CT and magnetic resonance angiography revealed the complete occlusion of the aneurysms bilaterally. Conclusion The use of a flow diverter appears to be an efficient and safe method to occlude carotid pseudoaneurysms even in an inflammatory milieu. PMID- 28992723 TI - Severe cerebellar hemorrhage following transverse sinus stenting for idiopathic intracranial hypertension. AB - We report a severe adverse event occurring in the course of a cohort study (ISRCTN13784335) aimed at measuring the efficacy and safety of venous stenting in the treatment of patients with medically refractory idiopathic intracranial hypertension (IIH). The patient was a 41-year-old woman who was not overweight, who presented with severe headache, grade 1 bilateral papilledema and transient tinnitus, refractory to medical treatment. Right transverse sinus stenting was successfully performed. Following surgery, the patient's state of consciousness decreased acutely with rapid and progressive loss of brainstem reflex. CT scan revealed acute cerebellar and intraventricular hemorrhage with obstructive hydrocephalus. Angioscan revealed normal venous sinus patency and cerebral MRI showed acute mesencephalic ischemia. Mechanical impairment of cerebellar venous drainage by the stent or venous perforation with the large guidewire used in this technique are two logical ways to explain the cerebellar hemorrhage seen in our patient. The risk of such a complication could probably be reduced using alternative tools and technique. However, given the low level of evidence around the safety of transverse sinus stenting in IIH, its formal assessment in clinical trials is required. PMID- 28992724 TI - Educational inequality in cardiovascular diseases: a sibling approach. AB - AIMS: Educational inequality in diseases in the circulatory system (here termed cardiovascular disease) is well documented but may be confounded by early life factors. The aim of this observational study was to examine whether the associations between education and all cardiovascular diseases, ischaemic heart disease and stroke, respectively, were explained by family factors shared by siblings. METHODS: The study population included all individuals born in Denmark between 1950 and 1979 who had at least one full sibling born in the same period. Using Cox regression, data were analysed in conventional cohort and within sibship analyses in which the association was examined within siblings discordant on education. Assuming that attenuation of associations in the within-sibship as compared with the cohort analyses would indicate confounding from factors shared within families. RESULTS: A lower educational status was associated with a higher risk of cardiovascular disease, ischaemic heart disease and stroke. All associations attenuated in the within-sibship analyses, in particular in the analyses on ischaemic heart disease before age 45 years. For instance, in the cohort analyses, the hazard rate of ischaemic heart disease among women less than 45 years who had a primary school education was 94% (hazard ratio 1.94 (1.78 2.12) higher than among those with a vocational education, while it attenuated to 51% (hazard ratio 1.51 (1.34-1.71)) in the within-sibship analysis. CONCLUSIONS: Confounding from factors shared by siblings explained the associations between education and the cardiovascular disease outcomes but to varying degrees. This should be taken into account when planning interventions aimed at reducing educational inequalities in the development of cardiovascular disease, ischaemic heart disease and stroke. PMID- 28992725 TI - Correction to: Olubajo F et al., Cranial subarachnoid and subdural haemorrhage caused by spinal melanoma metastasis. PMID- 28992726 TI - Middle Ear Histopathology Following Magnetic Delivery to the Cochlea of Prednisolone-loaded Iron Oxide Nanoparticles in Rats. AB - Delivery of therapy to the cochlea is a challenge and limits the efficacy of therapies meant to treat hearing loss, reverse tinnitus, and protect hearing from chemotherapy regimens. Magnetic injection is a technique that uses magnetic fields to inject nanoparticles from the middle ear into the cochlea, where they can then elute therapy to treat hearing disorders. To evaluate the safety of this treatment in the middle ear, 30 rats were subdivided into 6 groups and treated by single or multiple intratympanic injections of saline, prednisolone, nanoparticles, or nanoparticles loaded with prednisolone. A specially designed magnet array was used to magnetically inject the particles from the middle ear to the cochlea. Treatment began at study day 0, and animals were euthanized on study day 2, 30, or 90. Temporal bones were collected and prepared for histopathological examination. Intratympanic administration of magnetic nanoparticles and/or prednisolone resulted in minimal to mild inflammatory changes in all treated groups. The incidence and severity of the inflammatory changes observed appeared slightly increased in animals administered nanoparticles, with or without prednisolone, when compared to animals administered prednisolone alone. At study day 90, there was partial reversibility of the findings noted at study day 2 and 30. Repeat administration did not appear to cause greater inflammatory changes. PMID- 28992727 TI - Neuroendoscopic and histopathological correlation in 13 cases of cystic fluid filled brain tumours. AB - Neuroendoscopical images of fluid-filled cavity walls within encephalic tumours in thirteen adult patients were correlated with histopathology results of samples harvested during surgery. Extensive vascular proliferation, with mesh-like formations in a 3D pattern, as well as onionskin appearance, were observed in malignant tumours, as opposed to normal or slightly increased vascular pattern, observed in benign neoplasms. Medical facilities lacking sufficient technical resources where limited pathologist experience is expected, and can be associated with intraoperative histological misdiagnosis. Detailed high quality endoscopical observations of tumour cavity walls may be helpful to differentiate between benign and malignant lesions, and therefore, immediate surgical decisions can be made. PMID- 28992728 TI - Use of ex utero intrapartum treatment procedure in fetal neck and high airway anomalies - report of four clinical cases. AB - PURPOSE: To present antenatal management and use of ex utero intrapartum treatment (EXIT) in different fetal neck and high airway anomalies. MATERIAL AND METHODS: We have presented four different cases of fetal neck or airway pathology which were indications for EXIT, at our department. RESULTS: In three cases of fetal neck tumors, the primary precise antenatal diagnoses of tumors were confirmed after birth. The airways of all three fetuses were properly secured during EXIT by laryngologist. All these newborns survived. In the fourth case, a primary, antenatal diagnosis of congenital high airway obstruction syndrome due to severe trachea obstruction was not confirmed after birth. Finally, due to complete trachea dysgenesis, neither tracheoscopy nor tracheostomy was done during EXIT and the baby died. CONCLUSION: Despite a failure of intrapartum treatment in the fourth case, we strongly recommend this procedure for deliveries of fetuses with a suspicion of airway obstruction. PMID- 28992729 TI - Vessel wall MRI revealing inflammation on brain aneurysm associated to chronic mucocutaneous candidiasis. AB - Some authors have reported the association between CMC and brain aneurysms. In this paper it is reported a fusiform brain aneurysm associated to CMC and the vessel wall MRI findings. PMID- 28992736 TI - Reversal of Warfarin-Associated Life-Threatening Bleed With an Attenuated Dose of 4-Factor Prothrombin Complex Concentrate. PMID- 28992735 TI - I'm still standing: A longitudinal study on the effect of a default nudge. AB - OBJECTIVE: This study assessed the effect of a default nudge to reduce sedentary behaviour at work over time. DESIGN AND MAIN OUTCOME MEASURES: A field study was conducted at a governmental organisation. In the present study, the default setting of sit-stand desks (SSDs) was changed from sitting to standing height during a two-week intervention. Stand-up working rates were calculated based on observations that were done prior to, during, two weeks after and two months after the intervention. Additionally, a pre-measure survey (n = 606) and post measure survey (n = 354) were completed. Intention and social norms concerning stand-up working were compared for the 183 employees who completed both pre- and post-assessments (45.4% female, Mage = 44.21). RESULTS: Stand-up working rates raised from 1.82% in the baseline to 13.13% during the intervention. After the nudge was removed the percentage was 10.01% after two weeks and 7.78% after two months. A multilevel analysis indicated a significant increase in both intention and social norms after the nudge intervention. CONCLUSIONS: This study shows that a default nudge can increase stand-up working rates in offices with SSDs at least until two months after the nudge intervention. PMID- 28992737 TI - Asenapine, iloperidone and lurasidone exposures in young children reported to U.S. poison centers. AB - CONTEXT: Asenapine, iloperidone and lurasidone are relatively new atypical antipsychotics. There is limited information on toxicity on pediatric exposures to these drugs. The objective of this study was to compare toxicity associated with asenapine, iloperidone and lurasidone exposures in young children. METHODS: A retrospective study of U.S. National Poison Data System from 2010 to 2015 of single substance exposures to asenapine, iloperidone or lurasidone in children <6 years of age that were followed to known outcome was performed. RESULTS: There were 95 asenapine, 64 iloperidone and 124 lurasidone cases that met inclusion criteria. Reason was exploratory for 96% of cases. Drowsiness/lethargy occurred most frequently with iloperidone (45%) and least often with lurasidone (8%). Two iloperidone cases had respiratory depression. For asenapine, iloperidone and lurasidone, respectively, management sites were on-site non-health care facility (non-HCF) (32%, 16%, 26%), treated/discharged from emergency department (ED) (46%, 47%, 63%), admitted to noncritical care (9%, 14%, 10%) and admitted to critical care (10%, 22%, 2%). Clinical effect duration was 8 h or less for the majority of non-HCF cases (80%) and for children treated/discharged from the ED (72%). For asenapine, iloperidone and lurasidone, coded outcomes were no effect (50%, 41%, 81%), minor effect (43%, 39%, 17%), moderate (6%, 19%, 2%) and major (0, 2%, 0). DISCUSSION AND CONCLUSIONS: These findings suggest that in children under 6 years of age, lurasidone exposures were least serious and iloperidone exposures were most serious based on clinical effects, management sites and coded outcomes. Observation of symptomatic children in the ED for 8 h should be sufficient to make triage decisions based on persistence or resolution of clinical effects. PMID- 28992738 TI - Preliminary Validation of the HS-QoL: A Quality-of-Life Measure for Hidradenitis Suppurativa. AB - BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with adverse physical and psychosocial impacts. The development of an HS quality of-life measure, HS-QoL, has been recently described. OBJECTIVE: This study was designed to validate the HS-QoL. METHOD: Fifty-five patients with HS from 4 dermatology clinics completed the 30-minute online survey. Item reduction, reliability (internal consistency), and correlation analysis (to assess convergent validity) were conducted. RESULTS: The HS-QoL was reduced from 53 items to 44 items, resulting in a 7-subscale questionnaire. All subscales demonstrated excellent internal consistency, except for the support subscale, which had adequate internal consistency. All 7 HS-QoL subscales were related to other measures of QoL, life satisfaction, and mental health, which demonstrates convergent validity. CONCLUSION: The 44-item HS-QoL demonstrated strong preliminary evidence of reliability (internal consistency) and convergent validity. PMID- 28992739 TI - Pharmacogenetic and pharmacogenomic considerations of asthma treatment. AB - INTRODUCTION: Pharmacogenetic and pharmacogenomic approaches are already utilized in some areas, such as oncology and cardiovascular disease, for selecting appropriate patients and/or establishing treatment and dosing guidelines. This is not true in asthma although many patients have different responses to drug treatment due to genetic factors. Areas covered: Several genetic factors that affect the pharmacotherapeutic responses to asthma medications, such as beta2-AR agonists, corticosteroids, and leukotriene modifiers and could contribute to significant between-person variability in response are described. Expert opinion: An expanding number of genetic loci have been associated with therapeutic responses to asthma drugs but the individual effect of one single-nucleotide polymorphism is partial. In fact, epigenetic changes can modify genetic effects in time-, environment-, and tissue-specific manners, genes interact together in networks, and nongenetic components such as environmental exposures, gender, nutrients, and lifestyle can significantly interact with genetics to determine the response to therapy. Therefore, well-designed randomized controlled trials or observational studies are now mandatory to define if response to asthma medications in individual patients can be improved by using pharmacogenetic predictors of treatment response. Meanwhile, routine implementation of pharmacogenetics and pharmacogenomics into clinical practice remains a futuristic, far-off challenge for many clinical practices. PMID- 28992740 TI - Apoplexy of a collision tumour composed of subependymoma and cavernous-like malformation in the lateral ventricle: a case report. AB - Subependymomas are rare benign tumours arising from subependymal glial precursors that usually remain asymptomatic or may present due to obstruction of cerebrospinal fluid pathways. We describe the first report of intraventricular haemorrhage from subependymoma and cavernous-like malformation collision tumour in a 74-year-old male presented with an impaired level of consciousness. PMID- 28992741 TI - Neuropsychology and emotion processing in violent individuals with antisocial personality disorder or schizophrenia: The same or different? A systematic review and meta-analysis. AB - OBJECTIVES: To assess whether there are shared or divergent (a) cognitive and (b) emotion processing characteristics among violent individuals with antisocial personality disorder and/or schizophrenia, diagnoses which are commonly encountered at the interface of mental disorder and violence. Cognition and emotion processing are incorporated into models of violence, and thus an understanding of these characteristics within and between disorder groups may help inform future models and therapeutic targets. METHODS: Relevant databases (OVID, Embase, PsycINFO) were searched to identify suitable literature. Meta analyses comparing cognitive function in violent schizophrenia and antisocial personality disorder to healthy controls were conducted. Neuropsychological studies not comparing these groups to healthy controls, and emotion processing studies, were evaluated qualitatively. RESULTS: Meta-analyses indicated lower IQ, memory and executive function in both violent schizophrenia and antisocial personality disorder groups compared to healthy controls. The degree of deficit was consistently larger in violent schizophrenia. Both antisocial personality disorder and violent schizophrenia groups had difficulties in aspects of facial affect recognition, although theory of mind results were less conclusive. Psychopathic traits related positively to experiential emotion deficits across the two disorders. Very few studies explored comorbid violent schizophrenia and antisocial personality disorder despite this being common in clinical practice. CONCLUSION: There are qualitatively similar, but quantitatively different, neuropsychological and emotion processing deficits in violent individuals with schizophrenia and antisocial personality disorder which could be developed into transdiagnostic treatment targets for violent behaviour. Future research should aim to characterise specific subgroups of violent offenders, including those with comorbid diagnoses. PMID- 28992742 TI - The Effect of Peroneal Muscle Strength on Functional Outcomes After the Modified Brostrom Procedure for Chronic Ankle Instability. AB - BACKGROUND: Although the peroneal muscles are known to be the major dynamic lateral stabilizers of the ankle, little information is available regarding the change in muscle strength and relation with the outcomes after lateral ligament repair surgery. The purpose of this study was to identify the effects of peroneal strength on the validated functional outcome measures after the modified Brostrom procedure (MBP) for chronic ankle instability. METHODS: Forty-one patients (41 ankles) who underwent MBP using suture anchors were eligible and followed up to 2 years postoperatively. Functional evaluation consisted of the Foot and Ankle Outcome Score (FAOS), and Foot and Ankle Ability Measure (FAAM). The changes of peroneal strength were evaluated using an isokinetic dynamometer. Differences in the functional outcomes between the 3 groups divided according to the recovery rate of peroneal strength were analyzed. RESULTS: Peak torque and total work for eversion in 60 degrees/s angular velocity significantly improved from a mean 8.1 and 5.2 Nm preoperatively to 11.4 and 6.9 Nm at postoperative 2 years, respectively ( P < .001, P = .038). The deficit ratio of peak torque for eversion significantly improved from a mean 38.6% to 17.4%, and a significant side-to-side difference was found ( P = .011). There were no significant differences in FAOS, FAAM, and measurements of stress radiograph between the 3 groups. CONCLUSIONS: Although restoration of peroneal strength postoperatively was about 82.6% of the unaffected ankle, patient-reported function in daily and sport activities were satisfactorily improved. Postoperative isokinetic strength of the peroneals demonstrated no statistically significant effects on the functional outcomes after MBP. LEVEL OF EVIDENCE: Level III, prospective comparative case series. PMID- 28992743 TI - The knowledge and beliefs regarding practical aspects of cochlear implants: A study of otorhinolaryngologists in a secondary setting in a multi-country study. AB - OBJECTIVE: The main goal of this study was to determine the knowledge and beliefs of otorhinolaryngologists in a secondary setting in selected economically advanced European countries concerning severe hearing loss, hearing aids, and cochlear implants (CIs). Secondary goals of the study looked into the information sources of the otorhinolaryngologists and into key topics of importance for these professionals. In Europe, many adults, who could benefit from a CI, do not have one despite their availability via national health care systems. This lack of coverage might be due, in part, to the knowledge and beliefs of otorhinolaryngologists. METHODS: Otorhinolaryngologists in a secondary setting in Germany, England, France, Austria, and Sweden were emailed a custom-made questionnaire on their knowledge and beliefs regarding hearing loss and its treatments. Results were presented in relative frequencies (%) according to each nation. RESULTS: Two-hundred and forty otorhinolaryngologists responded (50 from each nation except Sweden). Each nation regarded rehabilitation and hearing preservation as particularly important in CIs. National and international conferences and conversations with colleagues were much more popular methods of keeping abreast of medical issues than other information sources such as online media or company information. CONCLUSION: The otorhinolaryngologists of the surveyed nations share many common beliefs about hearing loss, hearing aids, and CIs, although some national variation in opinion is present. The otorhinolaryngologists of each nation are knowledgeable, but could still benefit from an increased knowledge and awareness of hearing loss treatment modalities. PMID- 28992744 TI - Physician communication via Internet-enabled technology: A systematic review. AB - The use of Internet-enabled technology (information and communication technology such as smartphone applications) may enrich information exchange among providers and, consequently, improve health care delivery. The purpose of this systematic review was to gain a greater understanding of the role that Internet-enabled technology plays in enhancing communication among physicians. Studies were identified through a search in three electronic platforms: the Association for Computing Machinery Digital Library, ProQuest, and Web of Science. The search identified 5140 articles; of these, 21 met all inclusion criteria. In general, physicians were satisfied with Internet-enabled technology, but consensus was lacking regarding whether Internet-enabled technology improved efficiency or made a difference to clinical decision-making. Internet-enabled technology can play an important role in enhancing communication among physicians, but the extent of that benefit is influenced by (1) the impact of Internet-enabled technology on existing work practices, (2) the availability of adequate resources, and (3) the nature of institutional elements, such as privacy legislation. PMID- 28992745 TI - Are consistent juror decisions related to fast and frugal decision making? Investigating the relationship between juror consistency, decision speed and cue utilisation. AB - The aim of this study was to establish whether more consistent/accurate juror decision making is related to faster decision-making processes which use fewer cues - that is, fast and frugal heuristic processes. A correlational design was implemented with the co-variables: consistency of verdict decisions (participant decisions compared to the actual court verdicts), decision speed, and cue utilisation (the number of cues used to make a final verdict decision). Sixty participants read information about six murder trials which were based on real cases and whose outcome verdicts were deemed to be correct by the Scottish legal institution. Three of the cases had been handed down 'not guilty' verdicts, and three had been handed down 'guilty' verdicts. Participants read opening statements and were then presented with a block of prosecution evidence, followed by a block of defence evidence. They were then asked to make a final verdict. All three co-variables were significantly related. Cue utilisation and speed were positively correlated, as would be expected. Consistency was negatively and significantly related to both speed and cue utilisation. Partial correlations highlighted that cue utilisation was the only variable to have a significant relationship with consistency, and that the relationship between speed and consistency was a by-product of how frugal the juror was. Findings support the concept of frugal decisional processes being optimal within a juror context. The more frugal a decision is, the more likely jurors are to be to be accurate/consistent. PMID- 28992746 TI - Changes in sleep habits between 1985 and 2013 among children and adolescents in Sweden. AB - AIMS: The aim was to investigate changes in child and adolescent sleep habits in Sweden over time. This had not been done previously. METHODS: Cross-sectional questionnaire data over three decades of investigations of the Health Behaviours of School Children study (1985/1986, 2005/2006 and 2013/2014) were used. The sample included 18,682 children and adolescents, aged 11, 13 and 15. Empirically based age-specific sleep duration recommendations were used to operationalise sleep duration. RESULTS: The results showed that, over time, fewer go to bed early and more go to bed late. Regarding sleep duration, there have been decreases in the proportion of children and adolescents that sleep as much as is recommended for their age. Sleep onset difficulties have increased for all ages and increase the odds of sleeping less than recommended as well as having late bedtimes. Boys were more likely than girls to have later bedtimes and to sleep less than recommended. A vocational educational track, not planning to study further or being unsure of which track to choose increased the odds for 15 year olds to have late bedtimes and to sleep less than recommended compared with a college preparatory track. CONCLUSIONS: The results indicate that over time, fewer children and adolescents attain sufficient sleep duration. This may have implications for study results, mental health and cognitive abilities. PMID- 28992747 TI - Predictors and Moderators of Quality of Life Among College Students With ADHD. AB - OBJECTIVE: The current study examines (a) whether ADHD among college students is associated with differences in perceptions of quality of life (QoL); (b) the moderating roles of comorbidity, drug use, psychopharmacological treatment, and psychosocial treatment; and (c) the total impact of these variables on QoL. METHOD: Participants were college students with and without ADHD ( N = 372) in a longitudinal study. RESULTS: College students with ADHD were more likely to assert negative global QoL evaluations relative to non-ADHD peers. The relationship between ADHD and QoL was not altered as a function of medication treatment, comorbid psychopathology, psychosocial treatment, or drug use. CONCLUSION: College students with ADHD behave similarly to other adults with ADHD in that they make lower subjective global evaluations of their QoL relative to their non-ADHD agemates. Other factors associated with ADHD and QoL do not appear to moderate this relationship. PMID- 28992749 TI - A review of privacy and usability issues in mobile health systems: Role of external factors. AB - The increased penetration of mobile devices has created opportunities in the health sector and led to emerging of mobile health systems. As much as the mobile health systems have registered tremendous progress, they have been faced with privacy and usability issues. Due to the sensitivity of health information, there is an ethical need to equip mobile health systems with adequate privacy measures. However, these systems should also be useable by the intended users. Even though many researchers are working on solutions, the issues still persist. External factors such as cultural differences have also contributed to the issues, yet they have been under researched. In this article, we conduct a systematic literature review of 22 articles, categorize and present privacy and usability issues and possible solutions. We then discuss the relevance and implications of external factors to the findings on privacy and usability. We end with recommendations to address these external factors. PMID- 28992748 TI - Composition of the Stroma in the Human Endometrium and Endometriosis. AB - To analyze whether the endometrial and endometriotic microenvironment is involved in the pathogenesis of endometriosis, we characterized the stromal composition. We used CD90 for fibroblasts, alpha-smooth muscle actin for myofibroblasts as well as CD10 and CD140b for mesenchymal stromal cells. Quantification of eutopic endometrial stroma of cases without endometriosis showed a high percentage of stromal cells positive for CD140b (80.7%) and CD10 (67.4%), a moderate number of CD90-positive cells (57.9%), and very few alpha-smooth muscle actin-positive cells (8.5%). These values are highly similar to cases with endometriosis showing only minor changes: CD140b (76.7%), CD10 (63%), CD90 (53.9%), and alpha-smooth muscle actin (6.9%). There are no significant differences in the composition of CD140b- and CD10-positive stromal cells between the eutopic endometrial stroma and the 3 different endometriotic entities (ovarian, peritoneal, and deep infiltrating endometriosis), except for a significant difference between CD10 positive stromal cells in peritoneal lesions compared to ovarian lesions. However, the percentage of CD90-positive stromal cells was reduced in the 3 different endometriotic entities compared to the endometrium, especially significant in the ovarian lesions. In contrast, the percentage of alpha-smooth muscle actin-positive cells in the ovary was moderately increased. Taken together, the marker signature of eutopic endometrial and endometriotic stromal cells resembles mostly mesenchymal stromal cells. Our results show clearly that the proportion of the different stromal cell types in the endometrium with or without endometriosis does not differ significantly, thus suggesting that the stromal eutopic endometrial microenvironment does not contribute to the pathogenesis of endometriosis. PMID- 28992750 TI - Acute Hypotension After MitraClip Implantation due to Acute Left Ventricular Failure. AB - The MitraClip is a percutaneously implanted device approved for the treatment of symptomatic organic mitral regurgitation in poor surgical candidates. Despite its proven efficacy and safety for mitral regurgitation treatment, the MitraClip may unmask the true afterload of the left ventricle by removing the low-pressure left atrial system and may cause acute left ventricular systolic failure (afterload mismatch). Rapid diagnosis and treatment of afterload mismatch is crucial to ensure optimal patient outcomes. The authors present a case of acute hemodynamic deterioration after MitraClip implantation in a patient with chronic severe left ventricular systolic dysfunction. Transesophageal echocardiography was pivotal for the rapid recognition of acute left ventricular failure and aided in the intraoperative decision-making process and therapy. PMID- 28992751 TI - The care needs of postpartum women taking their first time of doing the month: a qualitative study. AB - BACKGROUND: In contemporary Taiwan, after giving birth, many women undertake a traditional postpartum practice called 'doing the month', which occurs in the medical context of postpartum nursing centres instead of at home. Thus, healthcare workers must identify and address the care needs of new mothers in this setting to improve the care of new mothers and their baby and family. AIM: To explore new mothers' care needs from their own perspectives during the period of doing the month. METHODS: A qualitative study was performed. Eligible participants recruited through purposive sampling were interviewed comprehensively. RESULTS: Twenty-seven primiparous women participated (mean age: 32 years; mean marriage length: 3.4 years). Four themes were identified: the need to increase energy to gain more yang force, the need to internalise mothering, the need to be supported by the family and friends, and the need to be understood. CONCLUSIONS: For effective care, sufficient support and guidance must be provided to first-time mothers and their families, especially when mother-baby rooming-in is the standard of care. PMID- 28992752 TI - Comorbid Internalizing and Externalizing Disorders Predict Lability of Negative Emotions Among Children With ADHD. AB - OBJECTIVE: A subset of children with ADHD experience more frequent, sudden, and intense shifts toward negative emotions. The current study utilized ecological momentary assessment (EMA) to provide a valid assessment of the impact of comorbid internalizing and externalizing disorders on negative emotional lability (EL) among children with ADHD. METHOD: Parents of 58, 8- to 12-year-old children with ADHD were administered a diagnostic interview to assess for ADHD and for the presence of comorbid disorders. Parents completed EMA-based ratings of their child's negative emotions three times daily for a total of 28 days. RESULTS: Children with a comorbid internalizing disorder or children with comorbid oppositional defiant disorder (ODD) experienced significantly greater EMA-derived negative EL than children without comorbid disorders over time. Children with multiple comorbidities experienced greater EL than children with single comorbidities. CONCLUSION: Overall, this study suggested that both comorbid ODD and comorbid internalizing disorders contribute to negative EL among children with ADHD. PMID- 28992753 TI - Pelvic vein embolisation of gonadal and internal iliac veins can be performed safely and with good technical results in an ambulatory vein clinic, under local anaesthetic alone - Results from two years' experience. AB - Objectives Pelvic vein embolisation is increasing in venous practice for the treatment of conditions associated with pelvic venous reflux. In July 2014, we introduced a local anaesthetic "walk-in walk-out" pelvic vein embolisation service situated in a vein clinic, remote from a hospital. Methods Prospective audit of all patients undergoing pelvic vein embolisation for pelvic venous reflux. All patients had serum urea and electrolytes tested before procedure. Embolisation coils used were interlock embolisation coils (Boston Scientific, USA) as they can be repositioned after deployment and before release. We noted (1) complications during or post-procedure (2) successful abolition of pelvic venous reflux on transvaginal duplex scanning (3) number of veins (territories) treated and number of coils used. Results In 24 months, 121 patients underwent pelvic vein embolisation. Three males were excluded as transvaginal duplex scanning was impossible and six females excluded due to lack of complete data. None of these nine had any complications. Of 112 females analysed, mean age 45 years (24-71), 104 were for leg varices, 48 vulval varices and 20 for pelvic congestion syndrome (some had more than one indication). There were no deaths or serious complications to 30 days. Two procedures were abandoned, one completed subsequently and one was technically successful on review. One more had transient bradycardia and one had a coil removed by snare during the procedure. The mean number of venous territories treated was 2.9 and a mean of 3.3 coils was used per territory. Conclusion Pelvic vein embolisation under local anaesthetic is safe and technically effective in a remote out-patient facility outside of a hospital. PMID- 28992754 TI - Suicidal Ideation and Related Factors Among Korean High School Students: A Focus on Cyber Addiction and School Bullying. AB - The purpose of the study was to explore the association among suicidal ideation, cyber addiction, and school bullying of Korean high school students. This descriptive cross-sectional study included 416 students. The data were collected using structured questionnaires on suicidal ideation, Internet and smartphone addiction, experiences of school bullying, impulsiveness, and depression. Students who were bullied (odds ratio [ OR] = 3.0, 95% CI [1.1, 8.4]) and more depressed ( OR = 10.8, 95% CI [2.4, 48.2]) were more likely to have higher scores for suicidal ideation; however, when a lower stringency was used, female gender ( OR = 2.3, 95% CI [1.3, 4.0]) and addiction to smartphones ( OR = 2.4, 95% CI [1.1, 5.4]) were also statistically significant contributors to the presence of suicidal ideation. Students with suicidal ideation that is higher than average, but lower than the classical thresholds for risk group designation, should also be carefully assessed for early detection and intervention. Cyber addiction may be a particularly significant contributor to suicidal ideation, in addition to bullying and depressive mood, among Korean adolescents. PMID- 28992756 TI - The Paradox of Safety in Medication Management. AB - The reduction of medication errors is largely dependent upon the structure of the medication management system and the role of the pharmacist in the acute care setting. The significance of this claim became evident in an ethnographic study of nurses' work in which data were generated from extensive observations, formal interviews, and document reviews. Each step of medication management-from ordering to administering-was microanalyzed, and spaces and places for error emerged. Results revealed medication errors defined by proximity to the patient. Pharmacists became a surprising "stop-gap" between the physicians and patients in the recognition and interception of medication errors occurring far removed from the bedside and did not formally support the reporting of these errors. Understanding the complexity of this process and the roles of involved personnel reminds us that there is presently no fool-proof plan for the reduction of medication errors and implies a culture of safety remains elusive. PMID- 28992755 TI - Drug-Mediated Shortening of Action Potentials in LQTS2 Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes. AB - Cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSCs) are now a well-established modality for modeling genetic disorders of the heart. This is especially so for long QT syndrome (LQTS), which is caused by perturbation of ion channel function, and can lead to fainting, malignant arrhythmias and sudden cardiac death. LQTS2 is caused by mutations in KCNH2, a gene whose protein product contributes to IKr (also known as HERG), which is the predominant repolarizing potassium current in CMs. beta-blockers are the mainstay treatment for patients with LQTS, functioning by reducing heart rate and arrhythmogenesis. However, they are not effective in around a quarter of LQTS2 patients, in part, because they do not correct the defining feature of the condition, which is excessively prolonged QT interval. Since new therapeutics are needed, in this report, we biopsied skin fibroblasts from a patient who was both genetically and clinically diagnosed with LQTS2. By producing LQTS-hiPSC-CMs, we assessed the impact of different drugs on action potential duration (APD), which is used as an in vitro surrogate for QT interval. Not surprisingly, the patient's own beta-blocker medication, propranolol, had a marginal effect on APD in the LQTS-hiPSC-CMs. However, APD could be significantly reduced by up to 19% with compounds that enhanced the IKr current by direct channel binding or by indirect mediation through the PPARdelta/protein 14-3-3 epsilon/HERG pathway. Drug-induced enhancement of an alternative potassium current, IKATP, also reduced APD by up to 21%. This study demonstrates the utility of LQTS-hiPSC-CMs in evaluating whether drugs can shorten APD and, importantly, shows that PPARdelta agonists may form a new class of therapeutics for this condition. PMID- 28992757 TI - Newborn cystic fibrosis screening in southeastern Mexico: Birth prevalence and novel CFTR gene variants. AB - OBJECTIVE: To use the results of the first five years of a cystic fibrosis newborn screening program to estimate the cystic fibrosis birth prevalence and spectrum of cystic fibrosis transmembrane conductance regulator ( CFTR) gene variants in Yucatan, Mexico. METHODS: Screening was performed from 2010 to 2015, using two-tier immunoreactive trypsinogen testing, followed by a sweat test. When sweat test values were >30 mmol/L, the CFTR gene was analyzed. RESULTS: Of 96,071 newborns screened, a second sample was requested in 119 cases. A sweat test was performed in 30 newborns, and 9 possible cases were detected (seven confirmed cystic fibrosis and two inconclusive). The most frequently detected CFTR pathogenic variant (5/14 cystic fibrosis alleles, 35.7%) was p.(Phe508del); novel p.(Ala559Pro) and p.(Thr1299Hisfs*29) pathogenic variants were found. CONCLUSIONS: Cystic fibrosis birth prevalence in southeastern Mexico is 1:13,724 newborns. Immunoreactive trypsinogen blood concentration is influenced by gestational age and by the time of sampling. The spectrum of CFTR gene variants in Yucatan is heterogeneous. PMID- 28992758 TI - Aldosterone breakthrough does not alter central hemodynamics. AB - INTRODUCTION: Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are widely used in congestive heart failure and chronic kidney disease, but up to 40% of patients will experience aldosterone breakthrough, with aldosterone levels rising above pre-treatment levels after 6-12 months of renin angiotensin-aldosterone system blockade. Aldosterone breakthrough has been associated with worsening congestive heart failure and chronic kidney disease, yet the pathophysiology remains unclear. Breakthrough has not been associated with elevated peripheral blood pressure, but no studies have assessed its effect on central blood pressure. METHODS: Nineteen subjects with well-controlled peripheral blood pressure on stable doses of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker had aldosterone levels checked and central blood pressure parameters measured using the SphygmoCor system. The central blood pressure parameters of subjects with or without breakthrough, defined as serum aldosterone >15 ng/dl, were compared. RESULTS: Of the 19 subjects, six had breakthrough with a mean aldosterone level of 33.8 ng/dl, and 13 were without breakthrough with a mean level of 7.1 ng/dl. There was no significant difference between the two groups in any central blood pressure parameter. CONCLUSIONS: We found no correlation between aldosterone breakthrough and central blood pressure. The clinical impact of aldosterone breakthrough likely depends on its non genomic, pro-fibrotic, pro-inflammatory effects rather than its regulation of extracellular volume. PMID- 28992759 TI - A Qualitative Evaluation of an Online Expert-Facilitated Course on Tobacco Dependence Treatment. AB - Qualitative evaluations of courses prove difficult due to low response rates. Online courses may permit the analysis of qualitative feedback provided by health care providers (HCPs) during and after the course is completed. This study describes the use of qualitative methods for an online continuing medical education (CME) course through the analysis of HCP feedback for the purpose of quality improvement. We used formative and summative feedback from HCPs about their self-reported experiences of completing an online expert-facilitated course on tobacco dependence treatment (the Training Enhancement in Applied Cessation Counselling and Health [TEACH] Project). Phenomenological, inductive, and deductive approaches were applied to develop themes. QSR NVivo 11 was used to analyze the themes derived from free-text comments and responses to open-ended questions. A total of 277 out of 287 participants (96.5%) completed the course evaluations and provided 690 comments focused on how to improve the program. Five themes emerged from the formative evaluations: overall quality, content, delivery method, support, and time. The majority of comments (22.6%) in the formative evaluation expressed satisfaction with overall course quality. Suggestions for improvement were mostly for course content and delivery method (20.4% and 17.8%, respectively). Five themes emerged from the summative evaluation: feedback related to learning objectives, interprofessional collaboration, future topics of relevance, overall modifications, and overall satisfaction. Comments on course content, website function, timing, and support were the identified areas for improvement. This study provides a model to evaluate the effectiveness of online educational interventions. Significantly, this constructive approach to evaluation allows CME providers to take rapid corrective action. PMID- 28992760 TI - 'Cochlear view' plain radiograph: A simple reliable positioning method. AB - INTRODUCTION: The plain 'cochlear view' radiograph for checking cochlear implant electrode coiling and depth of insertion is strongly influenced by positioning. The best accuracy and inter-observer agreement are achieved with the X-ray beam passing through the axis of the modiolus, which is perpendicular to the plane of the basal turn of the cochlea. The basal turn of the cochlea generally is 45 from the head's sagittal plane. OBJECTIVE: To describe a simple reliable technique of patient positioning to maximize the accuracy of postoperative radiographs in the evaluation of cochlear electrode insertion. METHODS: This is a description of patient positioning and radiographic technique for intra-operatively checking the position of the electrode array of a cochlear implant. For the surgery, the patient's head is rolled 60 degrees to the side, and the head stabilized in/on a Mayfield horseshoe headrest. For the X-ray, the operating table is rolled 15 degrees toward the operated ear. The central X-ray beam from the C-arm is directed from near the floor toward the ceiling, aiming for a mark 2 cm anterior to the external auditory meatus. DISCUSSION: Several plain radiograph views have been described to assess cochlear implant electrode array coiling in the cochlea and the depth of insertion of the electrodes. Images away from the 'cochlear view' not only are difficult to interpret but also falsely suggest malposition of the electrode array. The 'cochlear view' radiograph most accurately assessed the depth of insertion. CONCLUSION: This technique of getting the 'cochlear view' is simple and reliable. PMID- 28992761 TI - KRAS mutation testing in borderline ovarian tumors and low-grade ovarian carcinomas with a rapid, fully integrated molecular diagnostic system. AB - Epithelial ovarian neoplasms are a heterogeneous group of tumors, including various malignancies with distinct clinicopathologic and molecular features. Mutations in BRAF and KRAS genes are the most frequent genetic aberrations found in low-grade serous ovarian carcinomas and serous and mucinous borderline tumors. Implementation of targeted therapeutic strategies requires access to highly specific and highly sensitive diagnostic tests for rapid determination of mutation status. One candidate for such test is fully integrated, real-time polymerase chain reaction-based IdyllaTM system for quick and simple detection of KRAS mutations in formaldehyde fixed-paraffin embedded tumor samples. The primary aim of this study was to verify whether fully integrated real-time polymerase chain reaction-based Idylla system may be useful in determination of KRAS mutation status in patients with borderline ovarian tumors and low-grade ovarian carcinomas. The study included tissue specimens from 37 patients with histopathologically verified ovarian masses, operated on at the Department of Obstetrics and Gynecology, Nicolaus Copernicus University Collegium Medicum in Bydgoszcz (Poland) between January 2009 and June 2012. Based on histopathological examination of surgical specimens, 30 lesions were classified as low-grade ovarian carcinomas and 7 as borderline ovarian tumors. Seven patients examined with Idylla KRAS Mutation Test tested positive for KRAS mutation. No statistically significant association was found between the incidence of KRAS mutations and histopathological type of ovarian tumors. Mean survival of the study subjects was 48.51 months (range 3-60 months). Presence of KRAS mutation did not exert a significant effect on the duration of survival in our series. Our findings suggest that Idylla KRAS Mutation Test may be a useful tool for rapid detection of KRAS mutations in ovarian tumor tissue. PMID- 28992762 TI - Mutations in TET2 and DNMT3A genes are associated with changes in global and gene specific methylation in acute myeloid leukemia. AB - Acute myeloid leukemia is characterized by its high biological and clinical heterogeneity, which represents an important barrier for a precise disease classification and accurate therapy. While epigenetic aberrations play a pivotal role in acute myeloid leukemia pathophysiology, molecular signatures such as change in the DNA methylation patterns and genetic mutations in enzymes needed to the methylation process can also be helpful for classifying acute myeloid leukemia. Our study aims to unveil the relevance of DNMT3A and TET2 genes in global and specific methylation patterns in acute myeloid leukemia. Peripheral blood samples from 110 untreated patients with acute myeloid leukemia and 15 healthy control individuals were collected. Global 5-methylcytosine and 5 hydroxymethylcytosine in genomic DNA from peripheral blood leukocytes were measured by using the MethylFlashTM Quantification kits. DNMT3A and TET2 expression levels were evaluated by real-time quantitative polymerase chain reaction. The R882A hotspot of DNMT3A and exons 6-10 of TET2 were amplified by polymerase chain reaction and sequenced using the Sanger method. Methylation patterns of 16 gene promoters were evaluated by pyrosequencing after treating DNA with sodium bisulfite, and their transcriptional products were measured by real time quantitative polymerase chain reaction.Here, we demonstrate altered levels of 5-methylcytosine and 5-hydroxymethylcytosine and highly variable transcript levels of DNMT3A and TET2 in peripheral blood leukocytes from acute myeloid leukemia patients. We found a mutation prevalence of 2.7% for DNMT3A and 11.8% for TET2 in the Mexican population with this disease. The average overall survival of acute myeloid leukemia patients with DNMT3A mutations was only 4 months. In addition, we showed that mutations in DNMT3A and TET2 may cause irregular DNA methylation patterns and transcriptional expression levels in 16 genes known to be involved in acute myeloid leukemia pathogenesis. Our findings suggest that alterations in DNMT3A and TET2 may be associated with acute myeloid leukemia prognosis. Furthermore, alterations in these enzymes affect normal methylation patterns in acute myeloid leukemia- specific genes, which in turn, may influence patient survival. PMID- 28992763 TI - Hyperosmolar Potassium (K+) Treatment Suppresses Osteoarthritic Chondrocyte Catabolic and Inflammatory Protein Production in a 3-Dimensional In Vitro Model. AB - Objective The main goal of this study was to provide a proof-of-concept demonstrating that hyperosmolar K+ solutions can limit production of catabolic and inflammatory mediators in human osteoarthritic chondrocytes (OACs). Methods A 3-dimensional in vitro model with poly(ethylene glycol) diacrylate (PEGDA) hydrogels was used. Catabolic and pro-inflammatory protein production from encapsulated OACs was assessed following culture for 1 or 7 days in the presence or absence of 80 mM K+ gluconate, 80 mM sodium (Na+) gluconate, or 160 mM sucrose, each added to culture media (final osmolarity ~490 mOsm). Results Relative to untreated controls, OACs treated with hyperosmolar (80 mM Na+ gluconate or 160 mM sucrose) solutions produced lower levels of catabolic and inflammatory mediators in a marker- and time-dependent manner (i.e., MMP-9 after 1 day; MCP-1 after 7 days ( P <= 0.015)). In contrast, OAC treatment with 80 mM K+ gluconate reduced catabolic and inflammatory mediators to a greater extent (both the number of markers and degree of suppression) relative to untreated, Na+ gluconate, or sucrose controls (i.e., MMP-3, -9, -13, TIMP-1, MCP-1, and IL-8 after 1 day; MMP-1, -3, -9, -13, TIMP-1, MCP-1, and IL-8 after 7 days ( P <= 0.029). Conclusions Hyperosmolar K+ solutions are capable of attenuating protein production of catabolic and inflammatory OA markers, providing the proof-of concept needed for further development of a K+-based intra-articular injection for OA treatment. Moreover, K+ performed significantly better than Na+- or sucrose-based solutions, supporting the application of K+ toward improving irrigation solutions for joint surgery. PMID- 28992765 TI - Phenotyping of CYP 4501A2 Activity by Total Overnight Salivary Caffeine Assessment (TOSCA) in Patients on Warfarin Treatment: A Cross-Sectional Study. AB - Warfarin is an oral anticoagulant, commonly used for primary and secondary prevention of venous and arterial thromboembolic events. The drug is characterized by narrow therapeutic index, widespread individual variability in clinical response, and high rates of adverse events, particularly bleeding complications. For these reasons, a close monitoring of the dosage, using the frequent assessment of coagulation status by means of International Normalized Ratio value, is mandatory. Warfarin is metabolized by hepatic cytochrome P-450. High CYP 450 activity may lead to low drug concentration and requires high warfarin doses to reach efficacy; conversely, low CYP 450 activity is responsible for high drug concentration and needs for low doses to avoid potential toxicity risks. The major isoforms of CYP involved in the metabolism of warfarin sodium are CYP1A2 (for the R-warfarin) and CYP2C9 (for the S-warfarin). The probes for testing CYP1A2 are phenacetin and caffeine while for CYP2C9 tolbutamide. Although S-warfarin has major activity, it was decided to exclude its phenotyping for ethical issues, being mandatory to use a drug (tolbutamide). Instead, it was chosen to test the 1A2 isoform, as the activity of the latter isoform could be investigated by using caffeine contained in the caffeinated beverages. Specifically, a single-point concentration of salivary caffeine (total overnight salivary caffeine assessment [TOSCA]) after an overnight period of the caffeinated beverages abstinence was utilized. In the present study, 75 nonsmoker patients regularly receiving warfarin sodium were enrolled. The results have showed a significant association of the warfarin dose with TOSCA values (coefficient = -0.15, standard error = 0.04, 95% confidence interval = -0.24 to 0.06, t = -3.23, P = .002). In conclusion, the phenotyping of CYP1A2 by TOSCA could be useful, if further proven, to help manage patients on warfarin in order to lessen severe adverse events. PMID- 28992764 TI - Use of Guidelines for Reducing Stroke Risk in Patients With Nonvalvular Atrial Fibrillation: A Review From a Latin American Perspective. AB - Atrial fibrillation (AF) is a prominent risk factor for stroke and a leading cause of death and disability throughout Latin America. Contemporary evidence based guidelines for the management of AF and stroke incorporate the use of practical and relatively simple scoring methods to estimate both stroke and bleeding risk, in order to assist in matching patients with appropriate interventions. This review examines consistencies and differences among guidelines for reducing stroke risk in patients with AF, assessing the role of user-friendly scoring methods to determine appropriate patients for anticoagulation and other treatment options. Current options include warfarin and direct oral anticoagulants such as dabigatran, rivaroxaban, apixaban, and edoxaban. These agents have been found to be superior or noninferior to standard vitamin K antagonist anticoagulation in large randomized trials. Potential benefits of these agents mainly include lower ischemic stroke rates, reduced intracranial bleeding, no need for regular monitoring, and fewer drug-drug and drug-food interactions. Expert opinions regarding clinical situations for which data are presently lacking, such as emergency bleeding and stroke in anticoagulated patients, are also provided. Enhanced attention and adherence to evidence-based guidelines are essential components for a strategy to reduce stroke morbidity and mortality across Latin America. PMID- 28992766 TI - Health-Related Quality of Life and Association With Arthropathy in Greek Patients with Hemophilia. AB - Health-related quality of life (HRQoL) is increasingly implicated in contemporary hemophilia management. This study focuses on the assessment of HRQoL in Greek patients with hemophilia and the comparison with normative data from the general population, as well as on the extent arthropathy may affect the patients' HRQoL. One hundred and nine adult patients completed the Greek social functioning (SF 36) and Haem-A-QoL questionnaires. Arthropathy was assessed by both the World Federation of Hemophilia clinical score and Pettersson radiological score. The most impaired domains of Haem-A-QoL were sports/leisure (SL) and physical health (PH; mean scores 61.2 and 42.2, respectively). The patients experienced statistically significant lower mean scores in all SF-36 domains than the normative sample, especially in role physical (RPH), bodily pain (BP), and general health (GH) subscales. Among Haem-A-QoL subscales, SL and PH were found strongly associated with severity of arthropathy using both orthopedic scores ( P < .001), and maintained the statistical significance after adjustment for age ( P < .05). A poor orthopedic status was also negatively associated with certain SF 36 subscales. However, none of these correlations remained after adjustment with age. Compared to normative data from Greece, patients with hemophilia showed deterioration in all HRQoL subscales, with a more pronounced effect in RPH, BP, and GH subscales. Health-related quality of life was strongly influenced by arthropathy, mainly in the physical aspects of HRQoL. The use of the disease specific Haem-A-QoL tool can capture additional associations between HRQoL and hemophilic arthropathy. PMID- 28992767 TI - Sensitivity of expressive linguistic domains to surgery age and audibility of speech in preschoolers with cochlear implants. AB - OBJECTIVES: To determine whether relative delays among domains exist in the conversational use of vocabulary, syntax, and morphology by children with cochlear implants (CIs) and whether these were differentially affected by age of implantation (AOI) and the audibility of speech. METHODS: Participants in this short-term longitudinal study were 126 children with AOI of 6-38 months and a matched group of 30 children without hearing loss. Language samples of the same children at ages 3.5 and 4.5 were analyzed for the breadth of vocabulary and bound morphemes used, and sentence length. RESULTS: At both test ages, expressive language domains were delayed equally. Higher performance across domains was independently associated with younger AOI and better pre-implant-aided thresholds. No domain was affected differently by very early implantation, but bound morpheme breadth was associated with better CI-aided thresholds. Between 63 and 78% of children with AOI of 6-11 months scored close to hearing age-mates by 4.5, a level achieved by fewer than 25% of those with AOI of 19-24 months or later ages. DISCUSSION: Previous studies indicated greater language delays in the areas of morphology and syntax than those of vocabulary, with the earliest ages of implantation conferring the greatest benefit to those domains. The current design addressed inconsistency across studies in modes of communication used, presence/absence of other disabilities, and differences in language domains chosen as outcome measures. CONCLUSIONS: Linguistic domains benefitted equally from early implantation, regardless of the duration of auditory stimulation. Better pre-CI-aided hearing often compensated for later AOI. Bound morpheme use was greater with better CI-aided thresholds. PMID- 28992768 TI - Peripheral Artery Disease: What You Need to Know. AB - Synopsis Claudication from peripheral artery disease (PAD) may mimic or coexist with musculoskeletal conditions and represents an important diagnostic consideration in patients over 50 years of age. Physical therapists are optimally positioned to recognize this condition by incorporating a vascular history and physical examination in appropriately selected patients. Recognition of PAD is important both from the standpoint of addressing the ischemic risk to the limb and because PAD is associated with high cerebrovascular and cardiovascular risk. Therefore, multidisciplinary management of patients with PAD is essential. Extensive evidence supports treatment of PAD-related claudication with supervised exercise, and physical therapists are well positioned to play an important role in this treatment. J Orthop Sports Phys Ther 2017;47(12):957-964. Epub 9 Oct 2017. doi:10.2519/jospt.2017.7442. PMID- 28992769 TI - Knee Extensor Rate of Torque Development Before and After Arthroscopic Partial Meniscectomy, With Analysis of Neuromuscular Mechanisms. AB - Study Design Descriptive, prospective single-cohort longitudinal study. Background Though rapid torque development is essential in activities of daily living and sports, it hasn't been specifically tested by most physical therapists or incorporated into rehabilitation programs until late in the treatment process. Little evidence is available on quadriceps torque development capacity before and after arthroscopic knee surgery. Objectives To study knee extensor rate of torque development, contributing mechanisms, and associations with strength and patient reported outcomes before and during the first 6 weeks after arthroscopic partial meniscectomy. Methods Twenty subjects (mean +/- SD age, 42.3 +/- 13.7 years; body mass index, 26.6 +/- 3.1 kg/m2) were tested before surgery, and at 2 and 5 weeks after surgery. Quadriceps muscle volume, strength, activation, rate of torque development, and patient-reported outcomes were evaluated across the study period. Results Significant side-to-side differences in quadriceps strength and voluntary rate of torque development were observed at each time point (P<.05). Changes in muscle activity were associated with changes in rapid torque development capacity. Side-to-side rate of torque development deficits after surgery were associated with lower patient-reported outcomes scores. Conclusion Diminished rapid torque development capacity is common in arthroscopic meniscal debridement patients. This reduced capacity is associated with an inability to quickly recruit and drive the quadriceps muscles (neural mechanisms) and not muscle atrophy or other peripheral factors tested. Patient-reported outcomes are associated with quadriceps rate of torque development, but not strength or muscle size. Rapid torque development warrants greater attention in rehabilitation. J Orthop Sports Phys Ther 2017;47(12):945-956. Epub 9 Oct 2017. doi:10.2519/jospt.2017.7310. PMID- 28992770 TI - Influence of Demographics and Utilization of Physical Therapy Interventions on Clinical Outcomes and Revision Rates Following Anterior Cruciate Ligament Reconstruction. AB - Study Design Retrospective cohort from the Intermountain Healthcare system, January 2007 to December 2014. Background Recent evolutions in health care delivery are putting physical therapists in the forefront to be more responsible for providing high-quality rehabilitation care in a more cost-effective manner. Studies investigating the association between physical therapy visit utilization and outcomes in vulnerable patient populations following anterior cruciate ligament (ACL) reconstruction may provide useful insights. Objectives To examine the relationship between patient age, sex, physical therapy visit utilization, and physical therapy intervention charges with revision rates and patient reported outcomes in individuals following primary ACL reconstruction. Methods A sample of 660 patients who had an ACL reconstruction was identified through an electronic medical record database. Age and physical therapy visit utilization were categorized to examine effects between groups (20 years of age or younger, 21 to 34 years of age, 35 years of age or older; fewer than 9 visits, 9 to 14 visits, 15 or more visits). Multilevel mixed-effects linear models were conducted to compare differences between revision rates and patient-reported outcomes during the episode of care. Receiver operating characteristic curve analyses were also used to determine visit-number and charge-per-visit cut points to discriminate patients who achieved at least a minimal clinically important difference on the patient-reported outcomes. Results Of 660 patients, 22 (3.3%) had revision surgery. Compared with patients 20 years and younger, the incidence rate ratio of ACL reconstruction revision was lower in patients who were 35 years and older (85%) and 21 to 34 years (59%). Of 470 patients who attended physical therapy for longer than 3 months, change in Knee Outcome Survey activities of daily living subscale score was significantly lower among patients 20 years of age and younger and in the lowest visit category. Conclusion Achievement of favorable outcomes following ACL reconstruction may require categorization of patients beyond surgical diagnosis alone. Younger patients (aged 20 years or less) attending fewer physical therapy visits (fewer than 9) were more likely to have ACL revision surgery and had inferior patient-reported outcomes compared to older patients and those with higher physical therapy visit utilization. The study design of a retrospective cohort limits the ability to identify causal relationships. Additionally, this study was conducted in only 1 geographic region within a single health care delivery system, which may limit the generalizability of the results. Level of Evidence Prognosis, level 2c. J Orthop Sports Phys Ther 2017;47(11):834-844. Epub 9 Oct 2017. doi:10.2519/jospt.2017.7048. PMID- 28992771 TI - Reliability and Validity of the Hip Stability Isometric Test (HipSIT): A New Method to Assess Hip Posterolateral Muscle Strength. AB - Study Design Cross-sectional study. Background The Hip Stability Isometric Test (HipSIT) evaluates the strength of the hip posterolateral stabilizers in a position that favors greater activation of the gluteus maximus and gluteus medius and lower activation of the tensor fascia lata. Objectives To check the validity and reliability of the HipSIT and to evaluate the HipSIT in women with patellofemoral pain (PFP). Methods The HipSIT was evaluated with a handheld dynamometer. During testing, the participants were sidelying, with their legs positioned at 45 degrees of hip flexion and 90 degrees of knee flexion. Participants were instructed to raise the knee of the upper leg while keeping the upper and lower heels in contact. To establish reliability and validity, 49 women were tested with the HipSIT by 2 different evaluators on day 1, and then again 7 days later. The strength of the hip extensors, abductors, and external rotators was also evaluated. Twenty women with unilateral PFP were also evaluated. Results The HipSIT has excellent intrarater and interrater reliability. The standard error of measurement was 0.01 kgf/kg, and the minimal detectable change was 0.036 kgf/kg. The HipSIT showed good validity in isolated hip abduction, external rotation, and extension (P<.01). Women with PFP showed a 10% deficit in the HipSIT results for the symptomatic limb (P = .01). Conclusion The HipSIT showed excellent interrater and intrarater reliability, moderate to good validity in women, and was able to identify strength deficits in women with PFP. J Orthop Sports Phys Ther 2017;47(12):906-913. Epub 9 Oct 2017. doi:10.2519/jospt.2017.7274. PMID- 28992773 TI - Clinical Decision Making in the Management of Patients With Cervicogenic Dizziness: A Case Series. AB - Study Design Case series. Background Although growing recognition of cervicogenic dizziness (CGD) is emerging, there is still no gold standard for the diagnosis of CGD. The purpose of this case series is to describe the clinical decision making utilized in the management of 7 patients presenting with CGD. Case Description Patients presenting with neck pain and accompanying subjective symptoms, including dizziness, unsteadiness, light-headedness, and visual disturbance, were selected. Clinical evidence of a temporal relationship between neck pain and dizziness, with or without sensorimotor disturbances, was assessed. Clinical decision making followed a 4-step process, informed by the current available best evidence. Outcome measures included the numeric rating scale for dizziness and neck pain, the Dizziness Handicap Inventory, Patient-Specific Functional Scale, and global rating of change. Outcomes Seven patients (mean age, 57 years; range, 31-86 years; 7 female) completed physical therapy management at an average of 13 sessions (range, 8-30 sessions) over a mean of 7 weeks. Clinically meaningful improvements were observed in the numeric rating scale for dizziness (mean difference, 5.7; 95% confidence interval [CI]: 4.0, 7.5), neck pain (mean difference, 5.4; 95% CI: 3.8, 7.1), and the Dizziness Handicap Inventory (mean difference, 32.6; 95% CI: 12.9, 52.2) at discontinuation. Patients also demonstrated overall satisfaction via the Patient-Specific Functional Scale (mean difference, 9) and global rating of change (mean, +6). Discussion This case series describes the physical therapist decision making, management, and outcomes in patients with CGD. Further investigation is warranted to develop a valid clinical decision-making guideline to inform management of patients with CGD. Level of Evidence Diagnosis, therapy, level 4. J Orthop Sports Phys Ther 2017;47(11):874-884. Epub 9 Oct 2017. doi:10.2519/jospt.2017.7425. PMID- 28992772 TI - Hip Abductor Muscle Volume and Strength Differences Between Women With Chronic Hip Joint Pain and Asymptomatic Controls. AB - Study Design Secondary analysis, cross-sectional study. Background Chronic hip joint pain (CHJP) can lead to limitations in activity participation, but the musculoskeletal factors associated with the condition are relatively unknown. Understanding the factors associated with CHJP may help develop rehabilitation strategies to improve quality of life of individuals with long-term hip pain. Objectives To compare measures of hip abductor muscle volume and hip abductor muscle strength between women with CHJP and asymptomatic controls. Methods Thirty women, 15 with CHJP and 15 matched asymptomatic controls (age range, 18-40 years), participated in this study. Magnetic resonance imaging was used to determine the volume of the primary hip abductor muscles, consisting of the gluteus medius, gluteus minimus, a small portion of the gluteus maximus, and the tensor fascia latae, within a defined region of interest. Break tests were performed using a handheld dynamometer to assess hip abductor strength. During the strength test, the participant was positioned in sidelying with the involved hip in 15 degrees of abduction. Independent-samples t tests were used to compare muscle volume and strength values between those with CHJP and asymptomatic controls. Results Compared to asymptomatic controls, women with CHJP demonstrated significantly increased gluteal muscle volume (228 +/- 40 cm3 versus 199 +/- 29 cm3, P = .032), but decreased hip abductor strength (74.6 +/- 16.8 Nm versus 93.6 +/- 20.2 Nm, P = .009). There were no significant differences in tensor fascia lata muscle volume between the 2 groups (P = .640). Conclusion Women with CHJP appear to have larger gluteal muscle volume, but decreased hip abductor strength, compared to asymptomatic controls. J Orthop Sports Phys Ther 2017;47(12):923-930. Epub 9 Oct 2017. doi:10.2519/jospt.2017.7380. PMID- 28992774 TI - Treatment of a burn animal model with functionalized tridimensional electrospun biomaterials. AB - Laminin-functionalized poly-d,l-lactic acid scaffolds were produced. Following this, mesenchymal stem cells and keratinocytes were seeded on biomaterials for the in vivo experiments, where the biomaterials with or without cells were implanted. The analysis is comprised of the visual aspect and mean size of the lesion plus the histology and gene expression. The results showed that the cells occupied all the structure of the scaffolds in all the groups. After nine days of in vivo experiments, the defect size did not show statistical difference among the groups, although the groups with the poly-d,l-lactic acid/Lam biomaterial had the lowest lesion size and presented the best visual aspect of the wound. Gene expression analysis showed considerable increase of tumor growth factor beta 1 expression, increased vascular endothelial growth factor and balance of the BAX/Bcl-2 ratio when compared to the lesion group. Histological analysis showed well-formed tissue in the groups where the biomaterials and biomaterials plus cells were used. In some animals, in which biomaterials and cells were used, the epidermis was formed throughout the length of the wound. In conclusion, these biomaterials were found to be capable of providing support for the growth of cells and stimulated the healing of the skin, which was improved by the use of cells. PMID- 28992775 TI - Evaluation of N-phosphonium chitosan as a novel vaccine carrier for intramuscular immunization. AB - Chitosan, as a potential vaccine delivery material, has obtained much attention for immunization prevention and therapy. However, its poor water solubility brings inconvenience for the practical applications. To address this issue, researchers have carried out many chemical modifications to prepare water-soluble chitosan derivatives for vaccine delivery. In this work, we prepared a chitosan derivative N-phosphonium chitosan with excellent water solubility and explored its potential as an intramuscular vaccine delivery system by using ovalbumin as a model antigen. Different vaccine formulations were intramuscularly injected into test mice. Through an immunohistochemistry assay, N-phosphonium chitosan-based antigen formulation could promote antigen arrival from injection site to the secondary lymph organ spleen. Further immunization results showed that 1 mg/ml N phosphonium chitosan-based vaccine formulation could contribute to significantly higher level of antigen-specific immune responses, including higher antigen specific IgG antibody titer, splenocyte proliferation, and cytokines secretion (interferon-gamma, interleukin-10, and interleukin-4) by the splenocytes of the immunized mice. From the results, the water-soluble chitosan derivative N phosphonium chitosan could be developed as a potential antigen carrier for immunization prevention and therapy. PMID- 28992776 TI - RANZCP Congress 2017 - 'An invaluable experience' says PIF scholarship recipient, Sumana Thomson. PMID- 28992778 TI - Talking with Dr Warren Kealy-Bateman. PMID- 28992780 TI - Obituary: Professor Basil James. PMID- 28992781 TI - From the President. PMID- 28992782 TI - Upcoming RANZCP conferences. PMID- 28992783 TI - Getting 'back on the wagon' following clozapine-induced septuple whammy. PMID- 28992784 TI - An interview with Frances Dark on peer workers in the mental health setting. PMID- 28992786 TI - Migration and risk of psychosis in Australia. PMID- 28992788 TI - Pharmacological considerations related to smoke-free inpatient environments. PMID- 28992790 TI - Human exposure to polyhexamethylene guanidine phosphate from humidifiers in residential settings: Cause of serious lung disease. AB - Exposure to the humidifier disinfectant, polyhexamethylene guanidine phosphate (PHMG), in mists generated from ultrasonic humidifiers was studied in a simulation chamber and apartment rooms. PHMG is suspected as a causative agent of lung disease in Korea residences. In the simulation-chamber study, the amount of disinfectant discharged from three different ultrasonic humidifiers was measured. Mists generated at 1, 2, and 4 times the recommended amount of disinfectant were sampled with an impinger, and the effect of relative humidity (RH) on airborne disinfectant concentration was studied by changing RH from 60%-70% to 90%-100%. In addition, particle size distribution (PSD) in mists was measured by scanning mobility particle sizer (SMPS), aerodynamic particle sizer (APS), and Mastersizer. In the apartment study, mists generated from ultrasonic humidifiers were sampled for 6 h in small and large rooms during fall ( n = 10) and winter ( n = 15). In the simulation study, the humidifiers discharged 205 +/- 24.6 ml/h of mist at maximum capacity. Concentrations of airborne disinfectant increased with increasing concentration of disinfectant. RH affected airborne disinfectant concentration in the chamber, with increasing concentration with increasing RH. Below RH 70%, no airborne PHMG was detected. PHMG-containing mists generated from ultrasonic humidifier showed various sizes ranging from 149-157 nm to 690-740 nm to larger than 5.4 um by SMPS, APS, and Mastersizer, respectively. Surface area mean diameter measured by Mastersizer ranged from 5.39 um to 5.72 um. In the apartment study conducted during the fall, the geometric mean (GM) and geometric standard deviation (GSD) and arithmetic mean (AM) and standard deviation (SD) of airborne PHMG concentration were 3.22 + 5.13 ug/m3 and 8.26 +/- 12.18 ug/m3, respectively. In the winter, GM + GSD and AM +/- SD of airborne PHMG concentration were 0.21 + 2.11 ug/m3 and 0.35 +/- 0.62 ug/m3, respectively. RH and temperature in the apartment rooms for fall and winter were 22.5 +/- 1.7 degrees C, 74.5 +/- 15.6% and 22.0 +/- 2 degrees C, 51.1 +/- 12.9%, respectively. Different RHs in the fall and winter resulted in very different airborne concentrations of disinfectant in the apartment rooms. Exposure levels and PSD of mists generated from ultrasonic humidifiers in apartments are not sufficient to conclude that PHMG causes lung disease in Korean residences. PMID- 28992791 TI - Bisphenol A and di(2-ethylhexyl) phthalate exert divergent effects on apoptosis and the Wnt/beta-catenin pathway in zebrafish embryos: A possible mechanism of endocrine disrupting chemical action. AB - Polyethylene terephthalate (PET) and polycarbonate (PC) are the most commonly used plastics in water bottles. Di(2-ethylhexyl) phthalate (DEHP) is used as a plasticizer in PET plastics, and bisphenol A (BPA) is used to produce PC. Both DEHP and BPA are known for their potential endocrine disrupting effects. The Wnt/beta-catenin signaling pathway has important roles in cell proliferation, cell specification and cell fate determination during embryonic development. Recent reports suggest a link between the Wnt/beta-catenin signaling pathway and apoptosis. The aim of this study was to investigate the relation between Wnt/beta catenin signaling and apoptosis in the case of BPA and DEHP exposure in zebrafish embryos. Accordingly, in vivo cell death was assessed using acridine orange staining, and reverse transcription polymerase chain reaction was used to determine the expressions of wnt3a, gsk3beta and ccnd1. Proliferative cell nuclear antigen, beta-catenin and Wnt3a expressions were determined immunohistochemically. Vitellogenin levels were determined using Enzyme Linked ImmunoSorbent Assay (ELISA). Increased vitellogenin levels, apoptosis, and wnt3a and gsk3beta expressions were observed in BPA-exposed zebrafish embryos. Increased apoptosis in the BPA-exposed embryos may be due to the pro-apoptotic changes induced by Wnt3a, whereas DEHP might be suggested to have a minor effect as Wnt3a expression; vitellogenin levels and apoptosis did not increase significantly following exposure to DEHP. PMID- 28992792 TI - Evaluation of gamma radiation-induced DNA damage in Aedes aegypti using the comet assay. AB - The study was undertaken to evaluate gamma radiation-induced DNA damage in Aedes aegypti. The comet assay was employed to demonstrate the extent of DNA damage produced in adult male A. aegypti exposed to seven different doses of gamma radiation, ranging from 1 Gy to 50 Gy. DNA damage was measured as the percentage of comet tail DNA. A significant linear increase in DNA damage was observed in all samples; the extent of damage being proportional to the dose of gamma radiation the organism received, except in those treated with 1 Gy. The highest amount of DNA damage was noticed at 1 h postirradiation, which decreased gradually with time, that is, at 3, 6 and 12 h postirradiation. This may indicate repair of the damaged DNA and/or loss of heavily damaged cells as the postirradiation time increased. The comet assay serves as a sensitive and rapid technique to detect gamma radiation-induced DNA damage in A. aegypti. This could be used as a potential biomarker for environmental risk assessment. PMID- 28992794 TI - Medication adherence across the lifespan: Theory, methods, interventions and six grand challenges. PMID- 28992793 TI - The Short-Chain Fatty Acid Propionate Inhibits Adipogenic Differentiation of Human Chorion-Derived Mesenchymal Stem Cells Through the Free Fatty Acid Receptor 2. AB - Free fatty acid receptor 2 (FFAR2, also known as GPR43) is a G-protein-coupled receptor activated by short-chain fatty acids that are produced by gut microbiota through fermentation of nondigestible carbohydrates. FFAR2 functions as a metabolic sensor and is expressed in metabolically active tissues, such as adipose tissue. Earlier studies proved the connection between FFAR2 and adipocyte differentiation in mice. The aim of this study was to investigate the implication of FFAR2 receptor in adipogenesis in human chorion-derived mesenchymal stem cells (cMSCs). The short-chain fatty acid, propionate, and phenylacetamide a selective FFAR2 agonist resulted in a marked suppression of lipid droplet accumulation during the adipogenic differentiation of cMSCs. Western blot studies revealed that FFAR2 was detectable at any time point of the differentiation period. The direct involvement of FFAR2 in the differentiation into adipocytes was proven by the downregulation of its gene expression in cMSCs by lentiviral messenger RNA (mRNA) silencing transduction particles. Our results showed that a significant suppression in lipid accumulation upon FFAR2 agonist treatments was elicited by FFAR2-silencing. Based on these results we suggest that propionate inhibits the formation of adipocytes from MSCs and acts on adipogenesis predominantly via FFAR2. PMID- 28992795 TI - Role of disease and demographic factors as determinants of return migration: A nationwide register-based cohort study. AB - AIMS: A number of aspects of the health status of migrants who return to their country of origin have been explored in the literature; however, a more general description of the incidence of disease and demographic characteristics is lacking. The aim of this research was to contribute such a description. METHODS: A nationwide cohort study was conducted of 114,331 migrants who obtained residence in Denmark between 1 January 1993 and 31 December 2010. Demographic characteristics and ten disease groups were included as explanatory variables and hazards ratios for the association between return migration and disease incidence, as well as demographic characteristics, were estimated using Cox regressions. RESULTS: The tendency to return-migrate when ill was not the same among younger and elderly migrants; migrants <55 years of age had a significantly smaller propensity to return-migrate if they had suffered from a disease during the 18 years of follow-up compared with those who had not had a disease, whereas migrants >=55 years of age were more prone to return if ill. The likelihood of returning decreased with increasing comorbidity in both age groups. Among those who were <55 years of age, the tendency to return increased with age at obtainment of residence; among those who were >=55 years, more men than women return-migrated. CONCLUSIONS: In Denmark, younger migrants are less inclined to return-migrate if they are ill compared with healthy migrants, whereas elderly migrants are more inclined to return if ill. The returnees also differ demographically from non-returnees in various ways. PMID- 28992796 TI - Subcortical gray matter atrophy is associated with cognitive deficit in multiple sclerosis but not in systemic lupus erythematosus patients. AB - Cognitive impairment is a significant clinical problem both in multiple sclerosis (MS) and systemic lupus erythematosus (SLE) patients. In MS cognitive dysfunction has been associated with brain atrophy and total demyelinating lesion volume. In SLE cognitive impairment is much less understood, and its link to structural brain damage remains to be established. The aim of this study was to identify the relationship between subcortical gray matter volume and cognitive impairment in MS and SLE. We recruited 37 MS and 38 SLE patients matched by age, disease duration and educational level. Patients underwent magnetic resonance imaging (MRI) and a battery of psychometric tests. Severity of cognitive impairment was similar in both cohorts despite larger white matter lesion load in MS patients. Psychometric scores were associated with global and subcortical gray matter atrophy measures and lesion load in MS, but not in SLE. In SLE, the lack of a relationship between cognitive impairment and structural damage, defined either as atrophy or white matter lesions, indicates a different causal mechanism of cognitive deficit. PMID- 28992797 TI - Hydroxychloroquine desensitization, an effective method to overcome hypersensitivity-a multicenter experience. AB - Hydroxychloroquine (HCQ) is widely used to treat autoimmune/rheumatic diseases such as systemic lupus erythematosus (SLE). The immune modulation effects of HCQ have been highlighted as beneficial for maintaining remission of SLE as well as ameliorating skin, joint and other manifestations. Moreover, HCQ exposure for prolonged periods as well as during pregnancy is considered safe, therefore it is recommended for the vast majority of SLE patients. Although HCQ therapy requires follow-up by a specialist, its most common side effects are mild gastrointestinal disturbances, sensitivity to light and skin rashes. Of these side effects, hypersensitivity skin reactions have been suggested to play a role in reduced compliance to HCQ therapy. In the current study we present a two-stage HCQ desensitization protocol that was successfully implemented among 12 out of 13 patients. We exhibit that prolonged HCQ oral desensitization is an effective method for overcoming mild to moderate late hypersensitivity reactions and thoroughly address possible mechanisms of action. PMID- 28992798 TI - TLR9 (rs187084) polymorphism is neither under selection pressure and nor predisposed to systemic lupus erythematosus. PMID- 28992799 TI - Significant symptomatic improvement of subacute cutaneous lupus after testosterone therapy in a female-to-male transgender subject. PMID- 28992801 TI - Time trend and risk factors of avascular bone necrosis in patients with systemic lupus erythematosus: methodological issues. PMID- 28992800 TI - Antimalarial-induced cardiomyopathy: a systematic review of the literature. AB - Background Antimalarials (AMs) are widely used in the treatment of connective tissue diseases. Their main side effect is retinal damage, while heart disease has been described in isolated cases. The aim of this study is to systematically review the existing literature on AM-induced cardiomyopathy (AMIC). Methods The PubMed database was searched for heart biopsy-confirmed AMIC cases. Information on demographics, clinical presentation, concomitant AM-related toxicity, cardiological investigations, treatment and outcome were collected. Descriptive statistics were used. Results Forty-seven cases (42 females) were identified with a mean age at diagnosis 56.4 +/- 12.6 and mean AM treatment duration 12.7 +/- 8.2 years. Systemic lupus erythematosus ( n = 19) and rheumatoid arthritis ( n = 18) were the most common primary diseases. Clinical presentation was that of congestive heart failure in 77%, while eight patients presented with syncope (17%). Complete atrioventricular block was reported in 17 patients; 24 received a permanent pacemaker (51%). Impaired systolic function was detected in 52.8%, bi ventricular hypertrophy in 51.4% and restrictive filling pattern of the left ventricle in 18 patients. Cardiac magnetic resonance showed late gadolinium enhancement in seven cases, with a non-vascular pattern in the interventricular septum. Cardiomyocyte vacuolation was reported in all cases; intravacuolar lamellar and curvilinear bodies were observed in 46 (98%) and 42 (89.4%) respectively. Mortality rate was 45% (18/40). Conclusion AMIC is a rare, probably under-recognized, complication of prolonged AM treatment. It presents as a hypertrophic, restrictive cardiomyopathy with or without conduction abnormalities. Early recognition and drug withdrawal are critical with a survival rate of almost 55%. PMID- 28992802 TI - Preputial diverticulum dilation in a Goettingen minipig. AB - Preputial dilation is an infrequently reported condition in pigs. The pathophysiology and etiology is unclear. Causes for diverticulum dilation are proposed to be chronic preputial diverticulitis with subsequent fibrosis of the preputial cavity, phimosis of the preputial orifice or the preputial diverticulum, but the large majority of cases are reportedly idiopathic in nature. Surgical interventions include ablative procedures, but many cases are not treated because of an assumed lack of clinical relevance in pigs not used for breeding. We report a case of progressive preputial dilation that recurred after surgical intervention. Histopathological examination revealed no primary inflammatory condition, contrary to literature suggesting a role for inflammatory mediators in pathogenesis. Phimosis of the preputial orifice was noted post mortem and might be a contributing factor. These findings partially contradict the current assumptions in regards to pathophysiology and treatment choices in the literature and warrant further investigation into alternative therapeutic interventions for this condition. PMID- 28992803 TI - Collagen sponge functionalized with chimeric anti-BMP-2 monoclonal antibody mediates repair of nonunion tibia defects in a nonhuman primate model: An exploratory study. AB - Recombinant human bone morphogenetic protein (BMP)-2 is an FDA-approved therapy for nonunion tibia fracture, though it has a number of biological and practical disadvantages. Our research group has developed a novel tissue engineering strategy termed antibody-mediated osseous regeneration. This entails application of anti-BMP-2 monoclonal antibodies (mAbs) to capture endogenous BMP's to mediate in vivo bone formation. This has been documented in a number of animal models. The present exploratory study sought to investigate the application of antibody mediated osseous regeneration for repair of nonunion tibia defect in a nonhuman primate model. A 20 mm segmental osteotomy was performed in tibia of 6 Macaca fascicularis and was implanted with absorbable collagen sponge that was functionalized with chimeric anti-BMP-2 or isotype matched control mAb. Cone beam computed tomography (CBCT), histologic and histomorphometric analyses were performed 12 weeks post-operatively. CBCT analyzed by quantitative 3D volumetric analysis revealed that sites implanted with absorbable collagen sponge functionalized with anti-BMP-2 mAb demonstrated numerically higher mineralized tissue (408 +/- 127 mm3) compared with sites implanted with isotype matched control mAb (214 +/- 81 mm3), though the difference was not statistically significant ( p = 0.09). Histologic and histomorphometric analysis showed de novo bone formation with greater ( p < 0.01) percentage of bone volume in sites implanted with anti-BMP-2 (41.3 +/- 4.4%), compared with isotype matched control mAb (14.6 +/- 5.6%). Results from the present exploratory study provide evidence for the potential of anti-BMP-2 mAb to mediate repair of a large segmental tibia defects in a nonhuman primate model. Therapeutic antibodies have generally been shown to have great safety and efficacy profile, though their application in tissue engineering has been limited in the past. Following further investigation, anti-BMP-2 mAbs immobilized on appropriate scaffold may have application in repair of large skeletal defects without the need for exogenous growth factors. PMID- 28992804 TI - Surface modification of model hydrogel contact lenses with hyaluronic acid via thiol-ene "click" chemistry for enhancing surface characteristics. AB - Discontinuation of contact lens wear as a result of ocular dryness and discomfort is extremely common; as many as 26% of contact lens wearers discontinue use within the first year. While patients are generally satisfied with conventional hydrogel lenses, improving on-eye comfort continues to remain a goal. Surface modification with a biomimetic, ocular friendly hydrophilic layer of a wetting agent is hypothesized to improve the interfacial interactions of the contact lens with the ocular surface. In this work, the synthesis and characterization of poly(2-hydroxyethyl methacrylate) surfaces grafted with a hydrophilic layer of hyaluronic acid are described. The immobilization reaction involved the covalent attachment of thiolated hyaluronic acid (20 kDa) on acrylated poly(2-hydroxyethyl methacrylate) via nucleophile-initiated Michael addition thiol-ene "click" chemistry. The surface chemistry of the modified surfaces was analyzed by Fourier transform infrared spectroscopy-attenuated total reflectance and X-ray photoelectron spectroscopy. The appearance of N (1s) and S (2p) peaks on the low resolution X-ray photoelectron spectroscopy spectra confirmed successful immobilization of hyaluronic acid. Grafting hyaluronic acid to the poly(2 hydroxyethyl methacrylate) surfaces decreased the contact angle, the dehydration rate, and the amount of nonspecific sorption of lysozyme and albumin in comparison to pristine hydrogel materials, suggesting the development of more wettable surfaces with improved water-retentive and antifouling properties, while maintaining optical transparency (>92%). In vitro testing also showed excellent viability of human corneal epithelial cells with the hyaluronic acid-grafted poly(2-hydroxyethyl methacrylate) surfaces. Hence, surface modification with hyaluronic acid via thiol-ene "click" chemistry could be useful in improving contact lens surface properties, potentially alleviating symptoms of contact lens related dryness and discomfort during wear. PMID- 28992805 TI - The effects of liquid crystal-based composite substrates on cell functional responses of human umbilical cord-derived mesenchymal stem cells by mechano regulatory process. AB - Physical properties of extracellular matrix, including elasticity and microstructure, have been considered as important factors inducing stem cell differentiation. This study developed a novel type of liquid crystal-based matrix by combining the elastic property of polyurethane with viscoelastic liquid crystal to generate a soft elastic response resembling physical microenvironment of stem cell niche, and explored the mechano-driving cell behaviors. Addition of varying liquid crystal concentration (10 wt%, 30 wt% and 50 wt%) had great effects on surface morphology and elastic modulus of liquid crystal/ polyurethane composite substrates. Changes in microstructure and elastic modulus of the substrates could cause intense cell responses that influenced cell properties, including proliferation, adhesion, and osteogenic differentiation. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) cultured on both liquid crystal-10/polyurethane and liquid crystal-30/polyurethane substrates exhibited higher viability, more actin filament, and larger spreading area while liquid crystal-50/polyurethane substrates seemed not to favor cell attachment and spreading. Alkaline phosphatase activity and calcium deposition were significantly improved with hUC-MSCs on both liquid crystal-10/ polyurethane and liquid crystal-30/ polyurethane substrates, and the maximal alkaline phosphatase activity was observed in liquid crystal-10/ polyurethane while the lowest in liquid crystal-50/ polyurethane. Osteopontin was upregulated to a high level in both liquid crystal-10/ polyurethane and liquid crystal-30/ polyurethane groups after 14 days culturing; the maximal expression of osteocalcin and related transcription factor 2 were found in liquid crystal-10/ polyurethane group on day 21. Our findings revealed that hUC-MSCs could intensely sense the bioactive patterns and soft-matter feature of liquid crystal domains and subsequently modulated cell behaviors, which may prove useful in the development of new class of biomaterials for applications in tissue engineering and regenerative medicine. PMID- 28992806 TI - In vitro and in vivo evaluation of the duck's feet collagen sponge for hemostatic applications. AB - Recently different hemostatic agents have been developed, but most of them are ineffective in severe bleeding and expensive or cause safety concerns. In this study, we fabricated duck's feet collagen-based porous sponges and investigated its use as a hemostatic agent. We determined the sponge's physical and biological characteristics and compared with Avitene via scanning electron microscope analysis, water-uptake abilities and porosity test, and cytotoxicity assay. The duck's feet collagen/silk sponge showed a larger interconnected porous structure compared to others sponges. The duck's feet collagen/silk sponge also exhibited significantly higher porosity than Avitene. Hemostatic properties of the sponges were evaluated by whole blood clotting and rat femoral artery hemorrhage experiment. The addition of silk to duck's feet collagen showed better blood clotting ability than Avitene in vitro. However, rat femoral artery hemorrhage test showed a similar hemostatic property between the duck's feet collagen-based sponges and Avitene. We suggest that duck's feet collagen-based sponge can be effectively used for hemostatic applications. PMID- 28992807 TI - Associations between vitamin D, adiposity, and respiratory symptoms in chronic spinal cord injury. AB - Context/Objective Persons with chronic spinal cord injury (SCI) have an increased risk of respiratory-related morbidity and mortality and chronic respiratory symptoms are clinical markers of future respiratory disease. Therefore, we sought to assess potentially modifiable factors associated with respiratory symptoms, with a focus on circulating vitamin D and measures of body fat. Design Cross sectional study. Setting Veterans Affairs Medical Center. Participants Three hundred forty-three participants (282 men and 61 women) with chronic SCI participating in an epidemiologic study to assess factors influencing respiratory health recruited from VA Boston and the community. Methods Participants provided a blood sample, completed a respiratory health questionnaire, and underwent dual x-ray absorptiometry (DXA) to assess % body fat. Logistic regression was used to assess cross-sectional associations between respiratory symptoms and plasma vitamin D and measures of body fat with adjustment for a number of potential confounders. Outcome Measures Chronic cough, chronic phlegm, any wheeze, persistent wheeze. Results After adjustment for a number of confounders (including smoking), participants with greater %-android, gynoid, trunk, or total body fat had increased odds ratios for any wheeze and suggestive associations with persistent wheeze, but not with chronic cough or phlegm. Vitamin D levels were not associated with any of the respiratory symptoms. Conclusion Increased body fat, but not vitamin D, was associated with wheeze in chronic SCI independent of a number of covariates. PMID- 28992808 TI - Editorial:Role of Proteins and Peptides in the Virulence and Pathogenesis of Human and Plant Pathogens - PART I. PMID- 28992809 TI - Editorial:Nutrition Transition in Developing Countries: Focus on South Asia. PMID- 28992810 TI - Identifying research priorities for public health research to address health inequalities: use of Delphi-like survey methods. AB - BACKGROUND: In the funding of health research and public health research it is vital that research questions posed are important and that funded research meets a research need or a gap in evidence. Many methods are used in the identification of research priorities, however, these can be resource intensive, costly and logistically challenging. Identifying such research priorities can be particularly challenging for complex public health problems as there is a need to consult a number of experts across disciplines and with a range of expertise. This study investigated the use of Delphi-like survey methods in identifying important research priorities relating to health inequalities and framing tractable research questions for topic areas identified. METHODS: The study was conducted in two phases, both using Delphi-like survey methods. Firstly, public health professionals with an interest in health inequalities were asked to identify research priorities. Secondly academic researchers were asked to frame tractable research questions relating to the priorities identified. These research priorities identified using Delphi-like survey methods were subsequently compared to those identified using different methods. RESULTS: A total of 52 public health professionals and 21 academics across the United Kingdom agreed to take part. The response rates were high, from public health professionals across three survey rounds (69%, 50% and 40%) and from academics across one round (52%), indicating that participants were receptive to the method and motivated to respond. The themes identified as encompassing the most important research priorities were mental health, healthy environment and health behaviours. Within these themes, the topic areas that emerged most strongly included community interventions for prevention of mental health problems and the food and alcohol environment. Some responses received from academic researchers were (as requested) in the form of tractable research questions, whereas others contributed further potential topic areas instead. CONCLUSIONS: Delphi-like survey methods are practical and productive as a means of obtaining opinions from a wide number of relevant experts identifying potential priority topic areas for research; however, this method is less appropriate for framing tractable research questions. PMID- 28992811 TI - Cholera outbreak caused by drinking lake water contaminated with human faeces in Kaiso Village, Hoima District, Western Uganda, October 2015. AB - BACKGROUND: On 12 October 2015, a cholera outbreak involving 65 cases and two deaths was reported in a fishing village in Hoima District, Western Uganda. Despite initial response by the local health department, the outbreak persisted. We conducted an investigation to identify the source and mode of transmission, and recommend evidence-led interventions to control and prevent cholera outbreaks in this area. METHODS: We defined a suspected case as the onset of acute watery diarrhoea from 1 October to 2 November 2015 in a resident of Kaiso Village. A confirmed case was a suspected case who had Vibrio cholerae isolated from stool. We found cases by record review and active community case finding. We performed descriptive epidemiologic analysis for hypothesis generation. In an unmatched case-control study, we compared exposure histories of 61 cases and 126 controls randomly selected among asymptomatic village residents. We also conducted an environmental assessment and obtained meteorological data from a weather station. RESULTS: We identified 122 suspected cases, of which six were culture-confirmed, 47 were confirmed positive with a rapid diagnostic test and two died. The two deceased cases had onset of the disease on 2 October and 10 October, respectively. Heavy rainfall occurred on 7-11 October; a point-source outbreak occurred on 12-15 October, followed by continuous community transmission for two weeks. Village residents usually collected drinking water from three lakeshore points - A, B and C: 9.8% (6/61) of case-persons and 31% (39/126) of control persons were found to usually use point A, 21% (13/61) of case-persons and 37% (46/126) of control-persons were found to usually use point B (OR = 1.8, 95% CI: 0.64-5.3), and 69% (42/61) of case-persons and 33% (41/126) of control-persons were found to usually use point C (OR = 6.7; 95% CI: 2.5-17) for water collection. All case-persons (61/61) and 93% (117/126) of control-persons reportedly never treated/boiled drinking water (OR = infinity, 95% CI Fisher: 1.0 - infinity). The village's piped water system had been vandalised and open defecation was common due to a lack of latrines. The lake water was found to be contiminated due to a gully channel that washed the faeces into the lake at point C. CONCLUSIONS: This outbreak was likely caused by drinking lake water contaminated by faeces from a gully channel. We recommend treatment of drinking water, fixing the vandalised piped-water system and constructing latrines. PMID- 28992812 TI - The Team to Address Bariatric Care in Canadian Children (Team ABC3): Team Grant Research Proposal. AB - BACKGROUND: Severe obesity (SO) in Canadian children remains poorly understood. However, based on international data, the prevalence of SO appears to be increasing and is associated with a number of psychosocial, bio-mechanical, and cardiometabolic health risks. The purpose of our national Team to Address Bariatric Care in Canadian Children (Team ABC3) is to develop and lead a series of inter-related studies to enhance the understanding and management of SO in Canadian children and adolescents (0-18 years). METHODS/DESIGN: From 2015 to 2019, Team ABC3 will conduct a series of projects at the regional, provincial, and national levels using multiple methods and study designs to respond to key knowledge gaps by (i) generating evidence on the prevalence of SO and its impact on health services utilization in children using existing Canadian data sources from primary care settings, (ii) exploring contemporary definitions of SO that link with health outcomes, (iii) comparing and contrasting health risks across the continuum of SO, (iv) understanding potential barriers to and facilitators of treatment success in children with SO, and (v) examining innovative lifestyle and behavioral interventions designed to successfully manage SO in children and their families. Furthermore, to examine the impact of innovative interventions on the management SO, we will (vi) evaluate whether adding a health coach, who provides support via text, email, and/or phone, improves children's ability to adhere to a web-based weight management program and (vii) test the feasibility and impact of a community-based weight management program for pre-school children with SO and their parents that combines group-based parenting sessions with in-home visits. DISCUSSION: Our research aligns with national priorities in obesity research, brings together leading scientists, clinicians, and stakeholders from across Canada, and will inform health services delivery throughout the country to provide the best care possible for children with SO and their families. PMID- 28992813 TI - Erratum to: costs of major intracranial, gastrointestinal and other bleeding events in patients with atrial fibrillation - a nationwide cohort study. PMID- 28992814 TI - Field efficacy and safety of fluralaner solution for administration in drinking water for the treatment of poultry red mite (Dermanyssus gallinae) infestations in commercial flocks in Europe. AB - BACKGROUND: Welfare concerns, production losses caused by Dermanyssus gallinae, the poultry red mite (PRM), and widespread mite resistance to environmentally applied acaricides continue to drive an urgent need for new and effective control measures. Fluralaner is a novel systemic acaricide developed to address that need. A series of field studies was initiated to investigate the safety and efficacy of a fluralaner solution (10 mg/ml) administered in drinking water at a dose rate of 0.5 mg/kg on two occasions with a 7-day interval, for treatment of natural PRM infestations in chickens. METHODS: Blinded, negative-controlled studies were completed in Europe across eight layer, two breeder, and two replacement chicken farms. At each farm, two similar flocks were housed in similar PRM-infested units (either rooms within a building, or separate buildings) varying from 550 to 100,000 birds per unit. One unit at each farm was allocated to fluralaner treatment, administered in drinking water on Days 0 and 7. One unit remained untreated. Mite traps were placed throughout each unit on Days -1, 0 or 1, 3, 6, 9, and 13 or 14, then at weekly or two-weekly intervals, retrieved after 24 h and processed for mite counts. Efficacy at each farm was assessed by mean PRM count reductions from traps in treated units compared with those from control units. Production parameters and safety were also monitored. RESULTS: Efficacy was 95.3 to 99.8% on Day 3 and 97.8 to 100% on Day 9, thereafter remaining above 90% for 56 to 238 days after treatment initiation. Post-treatment improvement in egg-laying rate was greater by 0.9 to 12.6% in the treated group at 9 of the 10 layer or breeder farms. There were no treatment related adverse events. CONCLUSION: Fluralaner administered at 0.5 mg/kg via drinking water twice, 7 days apart, was well tolerated and highly efficacious against the PRM in naturally infested chickens representing a range of production types and management systems. The results indicate that this novel treatment has potential to be the cornerstone of an integrated approach to reducing or eliminating the welfare and productivity costs of this increasingly threatening pest. PMID- 28992815 TI - Correction to: Expression of factors involved in apoptosis and cell survival is correlated with enzymes synthesizing lysophosphatidic acid and its receptors in granulosa cells originating from different types of bovine ovarian follicles. PMID- 28992816 TI - A Theoretical Model of the Wnt Signaling Pathway in the Epithelial Mesenchymal Transition. AB - BACKGROUND: Following the formation of a primary carcinoma, neoplastic cells metastasize by undergoing the epithelial mesenchymal transition (EMT), which is triggered by cues from inflammatory and stromal cells in the microenvironment. EMT allows epithelial cells to lose their highly adhesive nature and instead adopt the spindle-like appearance, as well as the invasive and migratory behavior, of mesenchymal cells. We hypothesize that a bistable switch between the epithelial and mesenchymal phenotypes governs EMT, allowing the cell to maintain its mesenchymal phenotype even after it leaves the primary tumor microenvironment and EMT-inducing extracellular signal. RESULTS: This work presents a simple mathematical model of EMT, specifically the roles played by four key proteins in the Wnt signaling pathway: Dishevelled (Dvl), E-cadherin, beta-catenin, and Slug. The model predicts that following activation of the Wnt pathway, an epithelial cell in the primary carcinoma must attain a threshold level of membrane-bound Dvl to convert to the mesenchymal-like phenotype and maintain that phenotype once it has migrated away from the primary tumor. Furthermore, sensitivity analysis of the model suggests that in both the epithelial and the mesenchymal states, the steady state behavior of E-cadherin and the transcription factor Slug are sensitive to changes in the degradation rate of Slug, while E-cadherin is also sensitive to the IC50 (half-maximal) concentration of Slug necessary to inhibit E cadherin production. The steady state behavior of Slug exhibits sensitivity to changes in the rate at which it is induced by beta-catenin upon activation of the Wnt pathway. In the presence of sufficient amount of Wnt ligand, E-cadherin levels are sensitive to the ratio of the rate of Slug activation via beta-catenin to the IC50 concentration of Slug necessary to inhibit E-cadherin production. CONCLUSIONS: The sensitivity of E-cadherin to the degradation rate of Slug, as well as the IC50 concentration of Slug necessary to inhibit E-cadherin production, shows how the adhesive nature of the cell depends on finely-tuned regulation of Slug. By highlighting the role of beta-catenin in the activation of EMT and the relationship between E-cadherin and Slug, this model identifies critical parameters of therapeutic concern, such as the threshold level of Dvl necessary to inactivate the GSK-3beta complex mediating beta-catenin degradation, the rate at which beta-catenin translocates to the nucleus, and the IC50 concentration of Slug needed to inhibit E-cadherin production. PMID- 28992819 TI - TB-PCR and drug resistance pattern in BALF in smear-negative active pulmonary TB. AB - SETTING: A tertiary referral hospital in Bangkok, Thailand. OBJECTIVES: To evaluate the efficacy of a bronchoalveolar lavage fluid (BALF) tuberculosis (TB) polymerase chain reaction (PCR) assay for the diagnosis of sputum smear-negative pulmonary TB (PTB) and the usefulness of a drug-resistant (DR) TB-PCR assay compared with standard drug susceptibility testing (DST). DESIGN: BALF samples from 918 patients with acid-fast bacilli (AFB) negative sputum smears who underwent bronchoscopy for diagnostic evaluations of pulmonary diseases were prospectively determined for specific genetic elements of TB using the AnyplexTM MTB/NTM Real-Time Detection kit. Positive TB-PCR samples were subsequently evaluated for DR-TB using the Anyplex II MTB/MDR Detection kit. RESULTS: A total of 224 patients were finally diagnosed with PTB. The sensitivity, specificity, positive predictive value and negative predictive value of the TB-PCR assay were respectively 38.8%, 100%, 100%, and 83.5%. The TB-PCR assay was more sensitive than culture (30.4%) and smear (6.7%). Of the 68 TB-positive culture samples, three cases with either isoniazid (INH) or rifampicin (RMP) resistance were detected by DST. The Anyplex II MTB/MDR assay provided similar results. CONCLUSIONS: The BALF TB-PCR assay is a useful tool in the diagnosis of sputum smear-negative PTB. It can also provide INH and RMP susceptibility patterns similar to those of standard DST. PMID- 28992818 TI - A Model on the Contribution of School Assets to the Achievement of Adolescents' Well-Being and Academic Performance. AB - The aim of this study was to examine a model on the contribution of school assets on the development of adolescent's well-being and school success. The sample comprised 1944 adolescents (893 girls and 1051 boys) aged between 12 and 17 years (M = 14.4; SD = 1.13), from secondary schools in Western Andalusia, which completed some self-report questionnaires. The results of structural equation modeling showed the goodness of fit of the initial theoretical model. This model confirmed the importance of school connectedness as a key factor in the relationships between other school assets (social climate; clarity of the rules and values, and positive opportunities and empowerment) and commitment to learning, academic performance and life satisfaction. However, the re specification of the initial model considered two complementary paths with theoretical sense: first, a direct influence between clarity of the rules and values and commitment to learning, and second, between academic performance and life satisfaction. This model obtained better goodness of fit indices than the first one: chi2 = 16.32; gl = 8; p = .038; chi2/gl = 2.04; SRMR = .018; RSMEA = .023 (95% C.I. = .005; 040); NNFI = .98; CFI = .99. From our study, the need to invest in initiatives focused on the promotion of adolescents' links with their school emerges as a key goal to contribute towards, at the same time, both a good academic performance and a better life satisfaction. PMID- 28992820 TI - Lauren DePaul: Providing Remote Health Care. PMID- 28992821 TI - 2017 American Society of Consultant Pharmacists Annual Meeting & Exhibition Abstracts of Posters. PMID- 28992822 TI - Therapy Update for Insomnia in the Elderly. AB - OBJECTIVE: To offer an update on insomnia in older adults and treatment options. DATA SOURCES: A search of PubMed using the terms "insomnia" and "older adults" was performed. Current guidelines, review articles, and drug database and manufacturer package inserts were utilized to provide relevant information. STUDY SELECTION: All English-language articles from 2012 to February 2017 and their bibliographies were reviewed for relevance. Current guidelines from the American College of Physicians, the American Academy of Sleep Medicine, and the American Geriatrics Society's Beers criteria were reviewed. DATA SYNTHESIS: Insomnia is a frequent complaint in the elderly. Treatment guidelines for this specific population are lacking. Anticholinergics, doxepin > 6 mg, benzodiazepines (BZDs), and non BZD receptor agonists (BzDRAs) are potentially inappropriate drugs for older adults. For adults with chronic insomnia, sleep hygiene practices and cognitive behavioral therapy should be considered as the initial treatments. If drug therapy is required or desired, the guidelines recommend short-term uses of BZDs (triazolam or temazepam), BzDRAs, low-dose doxepin (<= 6 mg), ramelteon, or suvorexant. Risks and benefits of pharmacotherapy should be discussed with patients and caregivers prior to treatment initiation. Frequent and regular monitoring for adverse events is warranted to prevent detrimental outcomes. CONCLUSION: Nonpharmacologic interventions are the first-line therapy for adults with chronic insomnia. Short-term drug therapy may be considered as an alternative or add-on treatment. Hypnotic use is associated with harm and requires close monitoring, especially in older adults. PMID- 28992817 TI - Clinical recommendations for cardiovascular magnetic resonance mapping of T1, T2, T2* and extracellular volume: A consensus statement by the Society for Cardiovascular Magnetic Resonance (SCMR) endorsed by the European Association for Cardiovascular Imaging (EACVI). AB - Parametric mapping techniques provide a non-invasive tool for quantifying tissue alterations in myocardial disease in those eligible for cardiovascular magnetic resonance (CMR). Parametric mapping with CMR now permits the routine spatial visualization and quantification of changes in myocardial composition based on changes in T1, T2, and T2*(star) relaxation times and extracellular volume (ECV). These changes include specific disease pathways related to mainly intracellular disturbances of the cardiomyocyte (e.g., iron overload, or glycosphingolipid accumulation in Anderson-Fabry disease); extracellular disturbances in the myocardial interstitium (e.g., myocardial fibrosis or cardiac amyloidosis from accumulation of collagen or amyloid proteins, respectively); or both (myocardial edema with increased intracellular and/or extracellular water). Parametric mapping promises improvements in patient care through advances in quantitative diagnostics, inter- and intra-patient comparability, and relatedly improvements in treatment. There is a multitude of technical approaches and potential applications. This document provides a summary of the existing evidence for the clinical value of parametric mapping in the heart as of mid 2017, and gives recommendations for practical use in different clinical scenarios for scientists, clinicians, and CMR manufacturers. PMID- 28992823 TI - Impact of Music Therapy on Dementia Behaviors: A Literature Review. AB - Worldwide, dementia is the most important contributor to disability in elderly patients. Treating patients with dementia can be challenging for clinicians because of the numerous behavioral and psychological symptoms of dementia (BPSD). The Dementia Action Alliance and American Geriatrics Society Beers criteria promote nonpharmacological and behavioral treatments as first-line therapy to manage BPSD to avoid adverse events associated with antipsychotic medications. Some of the nonpharmacologic therapies proposed for BPSD include: music therapy (MT), light therapy, acupressure, aromatherapy, massage, and animal-assisted therapy. However, several are supported with only limited literature findings. Among these, MT has the most substantial data. MT has demonstrated benefit throughout mild-severe stages of dementia. The extended impact is attributed to associated brain pathology. MT's mode of delivery is essential to the evidencebased use of music interventions and delivery methods. The literature citations show that adequately trained individuals should ideally conduct several forms of MT to obtain optimal benefit. There are several studies investigating the impact of the various forms of MT on alleviating BPSD. Among the numerous reviewed studies, six trials and three meta-analyses were included in this article. While the literature conflicts, MT is noninvasive, poses little to no risk to patients, requires minimal training, and offers large potential for implementation in the patient-care setting. In addition, MT can have an important role in fostering student pharmacist development, because an emphasis on the aging demographic is becoming increasingly important. PMID- 28992824 TI - A Nationwide Study of Pharmacists' Perception of the Impact of Medicare Part D on the Pharmacist-Patient Relationship. AB - BACKGROUND: Medicare Part D was implemented in 2006, introducing change to the community pharmacy marketplace, with profound disruption to independent pharmacy operations across the United States. AIMS: To understand pharmacist perceptions about Part D and their perceived obligation to address Part D issues on behalf of their beneficiaries. METHODS: A nationwide, cross-sectional survey of pharmacists was conducted between April and July 2013. The 43-item online survey collected information about demographics, implications of Part D on community pharmacy and patients, and beliefs about ideal pharmacy practice. RESULTS: Pharmacists reported more responsibility to address prior authorization issues (55.3% strongly agree or agree) than dispensing preferred medications (43.5%) or addressing patient copayment issues (38.1%). Predictors of the perceived responsibility to assist patients varied and included practice site, pharmacist age, pharmacy prescription volume, and pharmacy financial performance. DISCUSSION: Financial concerns continue to be the most significant issue following Part D implementation. The degree to which pharmacists feel responsible for addressing patient Part D concerns is variable and dependent on a variety of factors. Pharmacists who felt a personal responsibility to address patient copayment issues reported a better pharmacy financial performance, a larger increase in prescription volume, and a better pharmacist-patient relationship since Part D implementation. CONCLUSION: Nationwide, Part D financial concerns remain significant. Pharmacists can assist patients with managing cost issues, which can help alleviate pharmacy financial concerns. Many pharmacists practicing at independent locations do not feel responsible for addressing patient cost concerns, which may inadvertently impart a negative financial effect upon their pharmacy. PMID- 28992825 TI - Pharmacist Role in Transitions of Care. PMID- 28992827 TI - Improving Sleep Quality Assessment Using Wearable Sensors by Including Information From Postural/Sleep Position Changes and Body Acceleration: A Comparison of Chest-Worn Sensors, Wrist Actigraphy, and Polysomnography. AB - STUDY OBJECTIVES: To improve sleep quality assessment using a single chest-worn sensor by extracting body acceleration and sleep position changes. METHODS: Sleep patterns of 21 participants (50.8 +/- 12.8 years, 47.8% female) with self reported sleep problems were simultaneously recorded using a chest sensor (Chest), an Actiwatch (Wrist), and polysomnography (PSG) during overnight sleep laboratory assessment. An algorithm for Chest was developed to detect sleep/wake epochs based on body acceleration and sleep position/postural changes data, which were then used to estimate sleep parameters of interest. Comparisons between Chest and Wrist with respect to PSG were performed. Identification of sleep/wake epochs was assessed by estimating sensitivity, specificity, and accuracy. Agreement between sensor-derived sleep parameters and PSG was assessed using correlation coefficients and Bland-Altman analysis. RESULTS: Chest identified sleep/wake epochs with an accuracy of on average 6% higher than Wrist (85.8% versus 79.8%). Similar trends were observed for sensitivity/specificity values. Correlation between Wrist and PSG was poor for most of the sleep parameters of interest (r = 0.0-0.3); however, Chest and PSG correlation showed moderate to strong agreement (r = 0.4-0.8) with relatively low bias and high precision bias (precision): 9.2 (13.2) minutes for sleep onset latency; 17.3(34.8) minutes for total sleep time; 7.5 (29.8) minutes for wake after sleep onset; and 2.0 (7.3)% for sleep efficacy. CONCLUSIONS: Combination of sleep postural/position changes and body acceleration improved detection of sleep/wake epochs compared to wrist acceleration alone. The chest sensors also improved estimation of sleep parameters of interest with stronger agreement with PSG. Our findings may expand the application of wearable sensors to clinically assess sleep outside of a sleep laboratory. PMID- 28992828 TI - Differences in Sleep Patterns and Problems by Race in a Clinical Sample of Black and White Preschoolers. AB - STUDY OBJECTIVES: Community-based research indicates that Black preschoolers tend to have more bedtime difficulties and are at higher risk for obstructive sleep apnea (OSA) compared to White preschoolers. This study examined differences in sleep patterns and problems by race among a clinical sample of Black and White preschoolers at an outpatient sleep clinic. METHODS: Data were collected from electronic medical records for 125 children ages 2-5 years (mean = 3.37 years, 64.0% White, 36.0% Black; 59.2% male) presenting at a pediatric sleep clinic in an academic medical center. Neighborhood income data were based on ZIP codes entered into the United States Census Bureau's American Fact Finder. RESULTS: Black patients (51.1%) were significantly more likely than White patients (20.0%) to bed-share with a caregiver (chi2 = 12.99, P <= .001). There were no other significant differences in presenting sleep patterns (bed/wake times, sleep onset latency, naps, night awakenings, or sleep opportunity). Logistic regressions showed that White patients were more likely to present with difficulty falling/staying asleep and receive an insomnia diagnosis, and Black patients were more likely to present with OSA-related concerns and receive a diagnosis of suspected OSA, even when controlling for relevant sociodemographic covariates. CONCLUSIONS: In contrast to community-based research, Black and White children showed similar sleep patterns. However, there were differences by race in referral questions and diagnoses. Findings suggest the need to consider caregiver perceptions and other sociocultural factors that may contribute to differential rates of presentation for sleep services, as well as potential health disparities in this regard. PMID- 28992829 TI - Night-to-Night Sleep Variability in Older Adults With Chronic Insomnia: Mediators and Moderators in a Randomized Controlled Trial of Brief Behavioral Therapy (BBT I). AB - STUDY OBJECTIVES: Sleep variability is a clinically significant variable in understanding and treating insomnia in older adults. The current study examined changes in sleep variability in the course of brief behavioral therapy for insomnia (BBT-I) in older adults who had chronic insomnia. Additionally, the current study examined the mediating mechanisms underlying reductions of sleep variability and the moderating effects of baseline sleep variability on treatment responsiveness. METHODS: Sixty-two elderly participants were randomly assigned to either BBT-I or self-monitoring and attention control (SMAC). Sleep was assessed by sleep diaries and actigraphy from baseline to posttreatment and at 3-month follow-up. Mixed models were used to examine changes in sleep variability (within person standard deviations of weekly sleep parameters) and the hypothesized mediation and moderation effects. RESULTS: Variabilities in sleep diary-assessed sleep onset latency (SOL) and actigraphy-assessed total sleep time (TST) significantly decreased in BBT-I compared to SMAC (Pseudo R2 = .12, .27; P = .018, .008). These effects were mediated by reductions in bedtime and wake time variability and time in bed. Significant time * group * baseline sleep variability interactions on sleep outcomes indicated that participants who had higher baseline sleep variability were more responsive to BBT-I; their actigraphy assessed TST, SOL, and sleep efficiency improved to a greater degree (Pseudo R2 = .15 to .66; P < .001 to .044). CONCLUSIONS: BBT-I is effective in reducing sleep variability in older adults who have chronic insomnia. Increased consistency in bedtime and wake time and decreased time in bed mediate reductions of sleep variability. Baseline sleep variability may serve as a marker of high treatment responsiveness to BBT-I. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT02967185. PMID- 28992830 TI - Perfectionism and Polysomnography-Determined Markers of Poor Sleep. AB - STUDY OBJECTIVES: Perfectionism has been suggested to represent a predisposing factor for poor sleep. However, previous studies have relied on self-reported measures. The association between perfectionism and poor sleep measured by polysomnography (PSG) warrants further investigation. METHODS: The current retrospective exploratory study used the Frost Multidimensional Perfectionism Scale and PSG in an unselected sample of 334 consecutive sleep laboratory patients (140 males, 194 females, 44.6 +/- 15.9 years). Data were analyzed using linear regression analyses. RESULTS: High levels of perfectionism were associated with PSG-determined markers of poor sleep in the first sleep laboratory night. The total Frost Multidimensional Perfectionism Scale score was significantly associated with the number of nocturnal awakenings in the first sleep laboratory night. The subscales "concern over mistakes" and "personal standards" of perfectionism were significantly associated with markers of poor sleep. In contrast, there were only a few associations between perfectionism and PSG variables of the second sleep laboratory night. CONCLUSIONS: This pattern of results suggests that high levels of perfectionism may predispose individuals to sleep disturbances in the context of acute stressors. Thus, the influence of perfectionism on poor sleep should be further investigated to improve treatment. PMID- 28992831 TI - Rate My Sleep: Examining the Information, Function, and Basis in Empirical Evidence Within Sleep Applications for Mobile Devices. AB - STUDY OBJECTIVES: Sleep applications (apps) have proliferated in online spaces, but few studies have examined the validity of the information contained within the apps. This study aimed to examine the information and functions found within sleep apps, determine if the information is based on empirical evidence, and whether or not user ratings were affected by these factors. METHODS: Sleep apps found in the Google Play store (n = 76) were coded using content analysis to examine the types of information, functions, and evidence base of each app. RESULTS: Only 32.9% of sleep apps contained empirical evidence supporting their claims, 15.8% contained clinical input, and 13.2% contained links to sleep literature. Apps also contained information on how sleep is affected by alcohol or drugs (23.7%), food (13.2%), daily activities (13.2), and stress (13.2%). A mean difference in average user rating was found between apps that contained at least one source of information compared those that did not. App user ratings were not associated with an app having multiple functions, or from an app drawing on multiple sources of evidence (except for sleep literature only). Last, there was a higher average user rating among apps that contained a sleep tip function. CONCLUSIONS: Sleep apps are increasingly popular, demonstrated by the large number of downloads in the Google Play store. Users favored apps that contained sleep tips; however, these tips and other information in the apps were generally not based on empirical evidence. Future research in the area of sleep apps should consider constructing sleep apps derived from empirical evidence and examining their effectiveness. PMID- 28992832 TI - Impact of Sleep-Disordered Breathing Treatment on Quality of Life Measures in a Large Clinic-Based Cohort. AB - STUDY OBJECTIVES: This study aims to report the effect of positive airway pressure (PAP) therapy on quality of life (QoL) measures in the clinical sleep disordered breathing (SDB) population. METHODS: We examined general QoL measures assessed by European Quality of Life-5D (EQ-5D) and sleep-specific QoL by examining Functional Outcomes of Sleep Questionnaire (FOSQ) scores before and after PAP therapy retrospectively in a clinical SDB population using paired and two-sample t tests. Age and socioeconomic status (SES) effect modification on pre PAP QoL measures were investigated utilizing the interaction terms. RESULTS: A total of 2,027 patients with SDB initiated PAP therapy between January 1, 2010 and December 31, 2014. The mean age of the cohort was 56.2 years (standard deviation = 13.2), with 45.8% female and 76.9% Caucasians. EQ-5D change after exclusion of those with normal QoL was 0.042 (0.152) in all patients, 0.051 (0.150) in patients who were PAP adherent by self-report, and 0.050 (0.132) in patients who were objectively PAP adherent (n = 704 of 1,011 with available objective adherence data, 69.6%). Change in FOSQ after excluding those with normal FOSQ was 1.9 (2.9) in all patients, 2.2 (2.9) in patients who were PAP adherent by self-report, and 2.3 (2.9) in patients who were objectively PAP adherent. Those with (1) worse QoL at baseline and younger age and (2) worse QoL at baseline and residing in lower SES strata had worse outcomes after PAP therapy (P < .05). CONCLUSIONS: We found consistent improvement in global and sleep specific QoL measures after PAP therapy, hence providing evidence of PAP benefit in the clinical population and rationale for targeted efforts to optimize QoL in younger and lower SES subgroups. PMID- 28992833 TI - Non-24-Hour Sleep-Wake Rhythm Disorder and Melatonin Secretion Impairment in a Patient With Pineal Cyst. AB - ABSTRACT: We report the case of a 14-year-old girl with a wide non-compressive pineal cyst, associated with the inability to control her sleep-wake schedule. Actigraphic monitoring showed a 24-hour free-running disorder (tau 26.96 hours). A 24-hour serum melatonin curve assay, with concomitant video-polysomnographic and body-core temperature monitoring, was performed. Melatonin curve showed a blunted nocturnal peak, lower total quantity of melatonin, and prolonged melatonin secretion in the morning, with normal temperature profile and sleep parameters. Treatment with melatonin up to 14 mg at bedtime was initiated with complete realignment of the sleep-wake rhythm (tau 23.93 hours). The role of the pineal cyst in the aforementioned alteration of melatonin secretion and free running disorder remains controversial, but our case supports the utility of monitoring sleep/wake, temperature, and melatonin rhythms in the diagnostic work up of pineal cysts associated with free-running disorder. PMID- 28992835 TI - A Patient With Rapidly Progressing Early-Onset Dementia and Insomnia. PMID- 28992834 TI - Prevalence of Cardiac Arrhythmias in Asian Patients With Obstructive Sleep Apnea: A Singapore Sleep Center Experience. AB - STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is associated with increased cardiovascular morbidity and mortality. Cardiac arrhythmias are common in patients with OSA. However, the prevalence and significance of cardiac arrhythmias in Asian patients with OSA are not well studied. The aim of this study is to determine the prevalence of cardiac arrhythmias in patients with OSA in Singapore and to evaluate possible factors that may predispose patients with OSA to arrhythmias. METHODS: A retrospective study of 2,019 patients was carried out from January 2011 to December 2012 at a sleep center in a tertiary medical center. Of the population, 1,457 patients were found to have OSA and 144 patients were found to have cardiac arrhythmias. Data collected included patient demographics, comorbidities, and polysomnogram parameters. RESULTS: The prevalence of cardiac arrhythmias in our OSA population is 8.0%, compared to that of primary snorers at 4.8% (P = .015). The univariate analysis revealed that older age, higher body mass index, comorbidities, and severity of OSA, including apnea-hypopnea index (AHI), lowest oxygen saturation (LSAT) and hypoxic time were correlated with a higher prevalence of cardiac arrhythmias (P < .05). However, the multivariate analysis showed that only age and body mass index were significantly correlated with arrhythmias. AHI, LSAT, and hypoxic time were no longer statistically significant. CONCLUSIONS: Our study demonstrated that cardiac arrhythmias are common in patients with OSA in Singapore. It also suggests that given the different demographics of our population, ethnicity may play a significant role in the development of cardiovascular disease among patients with OSA. COMMENTARY: A commentary on this article appears in this issue on page 1229. PMID- 28992837 TI - Infants Sleep for Brain. PMID- 28992836 TI - Carbamazepine Improves Apneic Episodes in Congenital Central Hypoventilation Syndrome (CCHS) With a Novel PHOX2B Exon 1 Missense Mutation. AB - ABSTRACT: Pathogenic variants in Paired-Like Homeobox 2B (PHOX2B) gene cause congenital central hypoventilation syndrome (CCHS), a rare disorder of the nervous system characterized by absent or reduced ventilatory response to hypoxia and hypercapnia. The focus of management in CCHS is optimizing ventilation. Thus far, no medication has proved effective in improving ventilation. Most CCHS cases are caused by polyalanine repeat expansion mutations. Non-polyalanine repeat expansion mutations are the cause in 8% of cases and result in a more severe clinical presentation. PHOX2B has 3 exons. Exon 3 of PHOX2B is the most common location for CCHS-causing mutations. Thus far, only 9 CCHS-causing mutations have been reported in exon 1, 8 of which were nonsense mutations. We report a child with CCHS who was found to have a novel heterozygous missense variant in exon 1; c.95A > T. Improvement in his apneic episodes was observed following treatment with carbamazepine. PMID- 28992838 TI - [Sparse knowledge about patient-reported outcomes after major emergency abdominal surgery]. AB - Little is known about patient-reported outcomes after major emergency abdominal surgery. Studies on patients undergoing major elective abdominal surgery and patients in the intensive care unit report significant challenges with chronic pain, functional impairment, quality of life, depression and post-traumatic stress disorder (PTSD). Approximately one out of three patients experience chronic pain and functional impairment after major emergency abdominal surgery. The magnitude of depression and PTSD after major emergency abdominal surgery have not been studied before. PMID- 28992839 TI - [Symptomatic zinc deficiency in a breast-fed infant]. AB - Nutrition containing zinc is of special practical importance in infants and children. Perinatal zinc deficiency manifestations include erosive dermatitis, alopecia, diarrhoea, central nervous system dysfunction and immune system deficiency. We present a case story of an ex-preterm, exclusively breast-fed infant who presented with irritability, clinical signs of infection, an atypical rash and signs of oral candidiasis. Blood tests showed low plasma levels of zinc and subsequent analysis showed reduced zinc levels in the breast milk. PMID- 28992840 TI - [Compression is important in erysipelas treatment]. AB - Erysipelas is a common skin infection involving the lymphatic vessels, which induces an oedema. This has a tendency of persisting after infection is treated. The lymphatic system plays an important role in the immune system, and the impaired lymph drainage leads to a state of local immune deficiency. This is essential to the pathogenesis of recurrent erysipelas, as each episode of erysipelas further damages the lymphatic system and increases the risk of a new infection. This vicious circle makes it important to treat both erysipelas and oedema appropriately to reduce recurrence and morbidity. PMID- 28992841 TI - [Umbilical endometriosis and tumours in umbilicus]. AB - Umbilical endometriosis is rare, representing only 0.5-1% of all cases of extragenital endometriosis. In infertile women, endometriosis may be as prevalent as 50%. Numerous differential diagnoses are present, hence the clinical diagnosis of umbilical tumours is intricate. In a 33-year-old woman, an umbilical tumour presented 12 months prior to referral. On referral, no cyclic bleeding was noticed, although intermittent bleeding and soreness of the element were present. Dysmenorrhoea, dyspareunia, intermittent pelvic pain, and three years of infertility were noted. A biopsy showed endometriosis. PMID- 28992842 TI - [Overtreatment and undertreatment of depression]. AB - The aim of this study was to examine what we know about the general practitioners' ability to diagnose and treat depression. Some studies suggest that clinicians might have considerable difficulty identifying depressions correctly, but that diagnostics become more accurate with increased severity of the disease. Several studies suggest that patients diagnosed with depression are undertreated, and some studies suggest that patients might receive antidepressants, even though they do not fulfil the International Classification of Diseases 10 criterion for depression. PMID- 28992843 TI - [Extracorporeal shock wave therapy in chronic Achilles tendinopathy]. AB - Extracorporeal shock wave therapy (ESWT) has shown promising results in treating epicondylitis lateralis humeri and fasciitis plantaris. This study investigates whether the evidence supports ESWT as part of the conservative treatment regime of chronic Achilles tendinopathy. The differences in diagnosing chronic Achilles tendinopathy, the use of different ESWT-machines and the difference in the evaluating methods for pain make it difficult to compare the studies. There is, however, a clear tendency toward ESWT having a positive treatment effect on chronic Achilles tendinopathy at both the insertion and the mid-portion. PMID- 28992844 TI - [Immunotherapy is cancer treatment with a novel side-effect profile]. AB - Within the last few years we have treated still more types of cancer with immune checkpoint inhibitors - anti-cytotoxic T-lymphocyte-associated-4 antibodies and anti-program-med cell death 1/anti-programmed cell death ligand 1 antibodies. A unique set of side effects called immune related adverse events irAEs may occur during treatment. Although severe irAEs remain rare they can become life threatening. Early detection of irAEs and initiation of relevant treatment are therefore crucial to reduce the risk of long-term seque-lae. We provide a detailed overview of irAEs and recommendations for treatment according to established guidelines. PMID- 28992845 TI - [Correct diagnostic of traumatic renal trauma is important for the treatment]. AB - Renal trauma is injury to the kidney because of either blunt or penetrating trauma. The condition must be diagnosed quickly and correctly in order to preserve kidney function. This article describes classification, diagnostics, treatment and follow-up. It is important to do a CT-urography to classify the injury properly. The majority of the patients with renal injury can be managed conservatively. Surgical exploration is primarily for the control of haemorrhage. Complications may require additional imaging or inter-ventions. Follow-up is focused on renal function and blood pressure. PMID- 28992846 TI - [Idiopathic oedema may cause many different clinical visits]. AB - Two patients with idiopathic oedema are presented describing their chronic tendency to accumulate fluid in the body and associated clinical features. One patient also tended to develop spontaneous purpura, which has been described in this condition. The other patient had an Odyssey in the healthcare system, before a final diagnosis of idiopathic oedema was reached and explained her different symptoms. Non-pharmacological interventions and various diuretics worked insufficiently, while ephedrine had an excellent efficacy in the second patient. PMID- 28992847 TI - [Rhabdomyolysis after isotretinoin treatment in a 17-year-old male]. AB - Rhabdomyolysis is a rare, but known complication to treat-ment with systemic isotretinoin in patients with acne and can lead to severe kidney damage. In our case report a 17-year-old male, exercising moderately, developed rhab-domyolysis without kidney injury after two-month treatment with isotretinoin 20 mg daily. He complained of some muscle pain and was treated according to guidelines for rhabdomyolysis with no sequelae. Frequent monitoring of muscle complaints and control of serum creatine kinase in patients with affected liver and kidney function is essential. PMID- 28992848 TI - The first report of human primary thoracic spine mast cell sarcoma: a case report. AB - In this report, we present a 53-year-old woman with primary mast cell sarcoma of the thoracic spine vertebrae. Mast cell sarcoma is an aggressive and rare cancer. To date, no cases of primary mast cell sarcoma have been reported in the spinal vertebrae. The patient initially presented with a 1-month history of pelvic and abdominal pain. Inconclusive gynecological evaluation resulted in a CT of the abdomen and pelvis, demonstrating a destructive lesion centered at the 11th thoracic vertebral body. The patient underwent a two-stage spine operation for T11 corpectomy and T7-L3 posterior spinal fusion. Histopathological, immunohistochemical, and flow cytometry studies of the resection specimens showed the tumor to be mostly composed of CD117-positive and mast cell tryptase-positive cells with features consistent with mast cell sarcoma. This is the first reported case of primary vertebral mast cell sarcoma, which may mimic other destructive lesions of the spine including osteomyelitis, vertebral tuberculosis, or plasmacytoma.?. PMID- 28992849 TI - Severe myoglobinuric acute kidney injury in a kidney recipient: rapid recovery after hemodialysis with the super high-flux membrane Theralite(r)?. AB - Myoglobinuric acute kidney injury (AKI) is a severe condition requiring early therapeutic strategies. Early recognition and treatment are crucial to reduce morbidity and mortality rate. Here, we report a kidney recipient with severe rhabdomyolysis and AKI secondary to parvovirus B19 infection. Initiation of hemodialysis with the super high-flux filter Theralite(r) (Gambro, cut off 45 kDa, 2.1 m2) resulted in the clearance of myoglobin from 61 to 71% after 3 hours. Elimination rates of IL-6 and beta2-microglobulin were ~ 30 - 64% and 55 - 71% after 3 hours, respectively. Renal graft function rapidly recovered. The place of this effective but expensive procedure still needs to be defined and validated in high-risk patients.?. PMID- 28992850 TI - Association of single-nucleotide polymorphism in the FKBP5 gene with response to steroids in pediatric patients with primary nephrotic syndrome?. AB - AIM: This study aimed to assess the association of single-nucleotide polymorphism (SNP) of FKBP5 with response to steroids in children with primary nephrotic syndrome (NS). MATERIALS AND METHODS: A total of 66 primary NS patients (cases) and 68 healthy individuals (controls) were enrolled in this study. The FKBP5 polymorphism rs4713916 (T/C) was analyzed by polymerase chain reaction (PCR) and sequencing after amplification of regions that potentially contain the SNP. The frequency of the FKBP5 (rs4713916) SNP as well as its relationship with response to steroids was investigated. RESULTS: The frequencies of the "TT" genotype starkly differed between the cases and controls (p = 0.024). The TT genotype showed overtly different frequency in the steroid-dependent NS group compared with controls (p = 0.041). CONCLUSION: The current data indicate that assessment of FKBP5 mutations could provide a basis for the identification of primary NS patients more likely to be efficiently treated with steroids.?. PMID- 28992852 TI - Beta-tricalcium phosphate and bone surgery: Editorial. PMID- 28992851 TI - Initiation of peritoneal dialysis in the first weeks after catheter insertion: A comparison of a neutral-pH, low-GDP PD fluid and a conventional PD fluid?. AB - BACKGROUND: Chronic exposure to peritoneal dialysis (PD) fluid is associated with development of functional and structural alterations of the peritoneal membrane. The exact time point at which these changes actually occur is not known. Whether changes to the peritoneum occur immediately after installation of PD fluids and whether there is a difference between neutral-pH, low glucose degradation product (low-GDP) PD fluids and conventional PD fluids is not known either. MATERIALS AND METHODS: We performed an observational study. Markers related to inflammation, fibrosis, mesothelial activation, and cytokines/growth factors were measured in effluents immediately after PD-catheter insertion and during the first days and weeks of PD treatment in patients using either dianeal(r) or physioneal(r). RESULTS: Peritoneal response was observed instantly upon insertion of the PD catheter and instillation of PD fluids and persisted during daily PD therapy. Particularly during the first contacts of the peritoneum with PD fluids, high levels of cytokines and biomarkers were observed. In general, CA125 is slightly higher with dianeal. There is no difference between the fluids in hyaluronic acid (HA), IL-6, IL-8, MCP-1, VEGF, and TGFbeta-1 levels. CONCLUSION: Implantation of the Tenckhoff catheter and installation of PD fluids induce inflammation, which in the first days resembles an acute inflammatory response. More continuous infusion of PD fluids further enhances peritoneal inflammation. The use of the bicarbonate/lactate-buffered, neutral-pH, low-GDP PD fluid physioneal exerts lower CA125 levels, lower D/P4 creatinine, but similar inflammatory response compared to conventional dianeal PD fluids in this early stage of PD therapy.?. PMID- 28992853 TI - Care Coordination and Transitions of Care. AB - Care coordination and effective transitions of care are essential for high quality care in cancer survivors. Aspects of care that require coordination include cancer surveillance, managing the effects of cancer and its treatment, and preventive care, including screening for new cancers, with the clinician responsible for each aspect of care clearly defined. There are many barriers to transitioning and coordinating care across cancer specialists and primary care physicians; possible solutions include survivorship care plans and certain care models. Improving these areas, along with survivorship care training and education, may lead to more effective care coordination and transitions in the future. PMID- 28992855 TI - Survivorship Issues in Adolescent and Young Adult Oncology. AB - Adolescent and young adult (AYA) individuals with a history of cancer make up a fraction of the total number of cancer survivors in the United States, but they represent a population with needs distinct from either the childhood or the older adult cancer populations. Fertility concerns, psychosocial factors, and health care access are just a few of the distinguishing characteristics. Caring for AYA cancer survivors presents unique opportunities for primary care providers to collaborate with oncology colleagues to minimize the long-term cancer burden. PMID- 28992854 TI - Long-Term and Latent Side Effects of Specific Cancer Types. AB - Although many cancer survivors diagnosed with early-stage disease will outlive their cancer, they may continue to experience long-term and/or latent side effects due to cancer treatment. Many of these side effects are common and contribute to worse quality of life, morbidity, and mortality for cancer survivors. This article summarizes the treatment side effects for several of the most prevalent cancers in the United States. PMID- 28992856 TI - Cancer-Related Fatigue in Cancer Survivorship. AB - Cancer-related fatigue (CRF) significantly interferes with usual functioning because of the distressing sense of physical, emotional, and cognitive exhaustion. Assessment of CRF is important and should be performed during the initial cancer diagnosis, throughout cancer treatment, and after treatment using a fatigue scoring scale (mild-severe). The general approach to CRF management applies to cancer survivors at all fatigue levels and includes education, counseling, and other strategies. Nonpharmacologic interventions include psychosocial interventions, exercise, yoga, physically based therapy, dietary management, and sleep therapy. Pharmacologic interventions include psychostimulants. Antidepressants may also benefit when CRF is accompanied by depression. PMID- 28992858 TI - Cognitive Changes Related to Cancer Therapy. AB - A growing population of cancer survivors is at risk for acute and long-term consequences resulting from cancer and its treatment. Cancer-related cognitive impairment (CRCI) typically manifests as modest deficits in attention, processing speed, executive functioning, and memory, which may persist for decades after treatment. Although some risk factors for CRCI are largely immutable (eg, genetics and demographic factors), there are many other contributors to CRCI that when appropriately addressed can result in improved cognitive functioning and quality of life. Neuropsychological assessment can help identify patient cognitive strengths and weaknesses, target psychological and behavioral contributors to CRCI, and guide treatment interventions. PMID- 28992859 TI - Hormonal Changes and Sexual Dysfunction. AB - Sexual dysfunction is a common concern for many patients with cancer after treatment. Hormonal changes as a result of cancer-directed therapy can affect both male and female sexual health. This has the potential to significantly impact patients' quality of life, but is underreported and undertreated in the oncology setting. This review discusses commonly reported sexual issues and the role that hormonal changes play in this dysfunction. Although medical and psychosocial intervention strategies exist, there is a clear need for further research to formally develop programming that can assist people whose sexual health has been impacted by cancer treatment. PMID- 28992857 TI - Anxiety and Depression in Cancer Survivors. AB - Most cancer survivors adjust well to life after cancer but some experience persisting negative mood, such as cancer-related fears, posttraumatic stress, anxiety, or depression. Mood fluctuations may not reach criteria for a clinical diagnosis but subclinical symptoms can interfere with quality of life. Women, adolescents, and young adults are particularly at risk for mood disturbances. Behavioral interventions, such as cognitive behavioral therapy and pharmacologic treatments, can effectively treat these distressing emotions. Much of the research on managing emotional needs after cancer has been completed with breast cancer survivors and more work is needed with diverse groups of survivors. PMID- 28992860 TI - Diet, Physical Activity, and Body Weight in Cancer Survivorship. AB - Diet, physical activity, and body weight have been shown to play an important role in cancer survivorship. The impact of each of these lifestyle factors differs slightly among cancer types, and adherence to recommended diet and physical activity guidelines has been associated with positive outcomes, including decrease in the risk of cancer recurrence and improvement of quality of life. Although there are compelling data that appropriate diet, physical activity, and body weight have beneficial effects in cancer survivorship, additional trials are needed to understand the relationship. PMID- 28992861 TI - Screening for Recurrence and Secondary Cancers. AB - The population of adult cancer survivors is increasing over time and they are at risk of developing recurrent and secondary cancers, even years after completion of treatment. Post-treatment care of survivors is increasingly the responsibility of primary care providers. Surveillance for recurrence and screening for secondary malignancies related to treatment depend largely on the primary malignancy, treatment regimen, and presence of a hereditary cancer syndrome, such as a BRCA mutation. This article presents surveillance strategies for the most common malignancies. PMID- 28992863 TI - A Lifelong Battle. PMID- 28992862 TI - Palliative Care for Cancer Survivors. AB - The palliative care approach for survivors begins with comprehensive assessment of communication and advance care planning needs and the physical, psychological and psychiatric, social, spiritual and religious, and cultural domains. Communication and decision-making about difficult issues should include responding to emotions, planning for future communication needs, and considering reasons for miscommunication. Key palliative approaches to symptom management include addressing physical and psychosocial concerns, and using nonpharmacologic approaches first or together with medications. Physicians should address advance care planning in older cancer survivors and those at significant risk of recurrence and mortality, ideally through ongoing conversations in a longitudinal care relationship. PMID- 28992864 TI - The Many Facets of Cancer Survivorship. PMID- 28992865 TI - My Approach to evaluating chest pain in the patient with no obstructive coronary artery disease. PMID- 28992866 TI - MY APPROACH to the patient with an infected implantable cardioverter defibrillator (ICD). PMID- 28992867 TI - Early Exclusion of Major Adverse Cardiac Events in Emergency Department Chest Pain Patients: A Prospective Observational Study. AB - BACKGROUND: The current evaluation of patients with chest pain presenting to an emergency department (ED) with suspected acute coronary syndrome (ACS) is a lengthy process involving serial measurements of troponin. OBJECTIVE: We aimed to validate the diagnostic accuracy of a Thrombolysis in Myocardial Infarction (TIMI) score with single high-sensitive cardiac troponin T (hs-cTnT) for early rule out of 30-day major adverse cardiac events (MACE), and to compare the TIMI score with combinations of heart-type fatty acid binding protein (H-FABP) and a modified HEART (history, electrocardiogram, age, risk factors, troponin) score. METHODS: We recruited 602 consecutive adult patients with chest pain and suspected ACS in the ED. Each patient had TIMI and HEART scores, and a point-of care H-FABP test. RESULTS: MACE occurred in 42 (7.0%) patients within 30 days. A low risk for 30-day MACE was identified by a modified TIMI score of 0 in 65 (11%) patients, and by a HEART score <= 2 in 96 (16%) patients. No MACE occurred in these groups, giving both scores a sensitivity of 100% (95% confidence interval [CI] 91.6-100%), and specificity of 11.6% (95% CI 9.2-14.5%) and 17.1% (95% CI 14.2-20.5%), respectively. Use of combined TIMI and HEART scores improved the specificity further to 22.0% (95% CI 18.7-25.6%) without lowering sensitivity. Early H-FABP measurement > 7 MUg/L had a sensitivity of 41.5% (95% CI 27.8-56.6%) and a specificity of 91.1% (95% CI 88.4-93.2%) for predicting 30-day MACE. CONCLUSIONS: A modified TIMI score of 0 or a HEART score of <= 2, incorporating a single hs-cTnT level, will identify patients with low risk of 30-day MACE for early discharge within 2 h of ED arrival. PMID- 28992868 TI - Definitive Diagnosis of Children Presenting to A Pediatric Emergency Department With Fever and Extremity Pain. AB - BACKGROUND: Children who present to the emergency department (ED) with complaint of fever and new-onset joint or extremity pain can be a diagnostic dilemma for many emergency and consulting physicians. OBJECTIVES: The purpose of our study was to identify the etiologies of pediatric fever and extremity pain presenting to a tertiary care pediatric ED and to define factors that were associated with advanced imaging, admission, and surgical intervention. METHODS: The electronic medical records of children presenting to our institution's pediatric ED with fever and extremity pain were retrospectively reviewed. Data collected included demographic characteristics, laboratory studies, diagnostic imaging, need for admission, and surgical procedures. RESULTS: The initial ED diagnosis was consistent with the definitive diagnosis 42% of the time. Children with the inability to bear weight on the affected limb were more likely to have a bacterial infection, such as osteomyelitis, septic arthritis, or intramuscular abscess (p = 0.016). An erythrocyte sedimentation rate >36 mm/hour and C-reactive protein levels >60 mg/L were found in children with osteomyelitis or septic arthritis (p = 0.043 and <0.001, respectively). Magnetic resonance imaging was ordered in 63% of children with multiple visits compared to 34% of children with a single visit (p = 0.05). CONCLUSIONS: In addition to a thorough history and physical examination, a complete set of laboratory studies and diagnostic imaging is necessary to reach an accurate diagnosis. The inability to bear weight, elevated C-reactive protein levels, and an elevated erythrocyte sedimentation rate are associated with bacterial infection. Magnetic resonance imaging is a useful imaging modality in determining an accurate diagnosis. PMID- 28992869 TI - Valproic Acid Overdose Review of a Case With Electrocardiographic Changes. AB - BACKGROUND: Valproic acid (VPA) is increasingly used to treat a variety of medical disorders, such as seizures, psychiatric disorders, and headaches. Therefore, accidental and intentional ingestions with valproic acid are increasing. OBJECTIVES: A case is presented in an adolescent with ischemic electrocardiographic changes after an acute overdose with VPA. DISCUSSION: Major features of a valproic acid overdose include respiratory depression, progressive coma, hepatotoxicity, thrombocytopenia, and hemodynamic instability. Electrocardiographic abnormalities usually consist of tachycardia and nonspecific changes. Supportive care is indicated in most overdoses and involves the monitoring and correction of electrolyte abnormalities, coagulopathies, and acid base imbalances. Treatment may include activated charcoal, naloxone, l-carnitine, and extracorporeal detoxification. CONCLUSIONS: Valproic acid overdose is a relatively rare and electrocardiographic changes usually consist of tachycardia and nonspecific changes, but ischemic changes may occur and usually transient and require only recognition. PMID- 28992870 TI - Evaluating Clinical Effectiveness and Pharmacokinetic Profile of Atomized Intranasal Midazolam in Children Undergoing Laceration Repair. AB - BACKGROUND: Atomized intranasal midazolam is a common adjunct in pediatrics for procedural anxiolysis. There are no previous studies of validated anxiety scores with pharmacokinetic data to support optimal procedure timing. OBJECTIVES: We describe the clinical and pharmacokinetic profile of atomized intranasal midazolam in children presenting for laceration repair. METHODS: Children 11 months to 7 years of age and weighing <26 kg received 0.4 mg/kg of atomized intranasal midazolam for simple laceration repair. Blood samples were obtained at 3 time points in each patient, and the data were fit with a 1-compartment model. Patient anxiety was rated with the Observational Scale of Behavioral Distress. Secondary outcomes included use of adjunctive medications, successful completion of procedure, and adverse events. RESULTS: Sixty-two subjects were enrolled, with a mean age of 3.3 years. The median time to peak midazolam concentration was 10.1 min (interquartile range 9.7-10.8 min), and the median time to the procedure was 26 min (interquartile range 21-34 min). There was a trend in higher Observational Scale of Behavioral Distress scores during the procedure. We observed a total of 2 adverse events, 1 episode of vomiting (1.6%) and 1 paradoxical reaction (1.6%). Procedural completion was successful in 97% of patients. CONCLUSIONS: Atomized intranasal midazolam is a safe and effective anxiolytic to facilitate laceration repair. The plasma concentration was >90% of the maximum from 5 to 17 min, suggesting this as an ideal procedural timeframe after intranasal midazolam administration. PMID- 28992871 TI - Emergency Decompression of Orbital Emphysema with Elevated Intraorbital Pressure. AB - BACKGROUND: A case of orbital emphysema associated with elevated intraorbital pressure, presenting as a complication of a paranasal sinus "blow-out" fracture after trauma to the orbit and globe is presented. CASE REPORT: A 45-year-old man developed left globe rupture with orbital emphysema after blunt trauma. A large air pocket in the superior orbit with medial wall fracture and globe tenting was identified on noncontrast computed tomography. Direct needle drainage was performed using a 23-gauge needle attached to a saline-filled syringe with the plunger removed. Rapid release of air bubbles with prompt alleviation of pressure symptoms was observed. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Early diagnosis and management of orbital emphysema can salvage useful function of the globe. The knowledge of this clinical entity and its management can prevent delay and unnecessary referral. PMID- 28992872 TI - Eczema Herpeticum. PMID- 28992873 TI - The Rapid Disaster Evaluation System (RaDES): A Plan to Improve Global Disaster Response by Privatizing the Assessment Component. AB - BACKGROUND: Emergency medicine personnel frequently respond to major disasters. They expect to have an effective and efficient management system to elegantly allocate available resources. Despite claims to the contrary, experience demonstrates this rarely occurs. OBJECTIVES: This article describes privatizing disaster assessment using a single-purposed, accountable, and well-trained organization. The goal is to achieve elegant disaster assessment, rather than repeatedly exhorting existing groups to do it. DISCUSSION: The Rapid Disaster Evaluation System (RaDES) would quickly and efficiently assess a postdisaster population's needs. It would use an accountable nongovernmental agency's teams with maximal training, mobility, and flexibility. Designed to augment the Inter Agency Standing Committee's 2015 Emergency Response Preparedness Plan, RaDES would provide the initial information needed to avoid haphazard and overlapping disaster responses. Rapidly deployed teams would gather information from multiple sources and continually communicate those findings to their base, which would then disseminate them to disaster coordinators in a concise, coherent, and transparent way. CONCLUSIONS: The RaDES concept represents an elegant, minimally bureaucratic, and effective rapid response to major disasters. However, its implementation faces logistical, funding, and political obstacles. Developing and maintaining RaDES would require significant funding and political commitment to coordinate the numerous agencies that claim to be performing the same tasks. Although simulations can demonstrate efficacy and deficiencies, only field tests will demonstrate RaDES' power to improve interagency coordination and decrease the cost of major disaster response. At the least, the RaDES concept should serve as a model for discussing how to practicably improve our current chaotic disaster responses. PMID- 28992874 TI - Poisoning after Ingestion of Spartium junceum Seeds: Dose-Dependent Effects in Three Boys. AB - BACKGROUND: Spanish broom (Spartium junceum L.) is an ornamental, medicinal, and potentially poisonous plant. CASE REPORT: Three children, aged 5-6 years, were accidentally poisoned from ingesting a variable number of seeds of Spanish broom. This plant contains several quinolizidine alkaloids as cytisine, which act as an agonist of nicotinic acetylcholine receptors. The potential danger varies, depending on the dose. After having ingested one to two seeds, one of the boys was asymptomatic. A second boy ingested four to five seeds and presented some digestive problems with favorable clinical evolution. A third boy ingested seven to eight seeds, and presented with digestive and neurologic symptoms, as well as minor metabolic acidosis. In this case there was vomiting with remains of the seeds. He responded well to a gastric lavage and activated charcoal. He was discharged 24 h post ingestion. The intake within one to eight seeds was accompanied by moderate symptoms, with good response to treatment. Children poisoned by plants with nicotine-like symptomatology usually fully recover, but some fatal cases have been reported. Prevention is always a key aspect to consider so as to reduce the risk of poisoning. There is a lack of legislative measures, based on lists provided by experts, to regulate real or potentially poisonous plants in children's areas. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case serves as an example of accidental plant poisoning. For emergency physicians, it is usually complicated to identify the specific plant involved, so initial treatment often starts with basic measures (airway, breathing, and circulation). PMID- 28992875 TI - The Sound of Free Air. PMID- 28992876 TI - Sparks of the CRISPR explosion: Applications in medicine and agriculture. PMID- 28992877 TI - Perioperative fluid management in major hepatic resection: an integrative review. AB - BACKGROUND: Fluid intervention and vasoactive pharmacological support during hepatic resection depend on the preference of the attending clinician, institutional resources, and practice culture. Evidence-based recommendations to guide perioperative fluid management are currently limited. Therefore, we provide a contemporary clinical integrative overview of the fundamental principles underpinning fluid intervention and hemodynamic optimization for adult patients undergoing major hepatic resection. DATA SOURCES: A literature review was performed of MEDLINE, EMBASE and the Cochrane Central Registry of Controlled Trials using the terms "surgery", "anesthesia", "starch", "hydroxyethyl starch derivatives", "albumin", "gelatin", "liver resection", "hepatic resection", "fluids", "fluid therapy", "crystalloid", "colloid", "saline", "plasma-Lyte", "plasmalyte", "hartmann's", "acetate", and "lactate". Search results for MEDLINE and EMBASE were additionally limited to studies on human populations that included adult age groups and publications in English. RESULTS: A total of 113 articles were included after appropriate inclusion criteria screening. Perioperative fluid management as it relates to various anesthetic and surgical techniques is discussed. CONCLUSIONS: Clinicians should have a fundamental understanding of the surgical phases of the resection, hemodynamic goals, and anesthesia challenges in attempts to individualize therapy to the patient's underlying pathophysiological condition. Therefore, an ideal approach for perioperative fluid therapy is always individualized. Planning and designing large-scale clinical trials are imperative to define the optimal type and amount of fluid for patients undergoing major hepatic resection. Further clinical trials evaluating different intraoperative goal-directed strategies are also eagerly awaited. PMID- 28992878 TI - Peginterferon alfa-2a for the treatment of chronic hepatitis C in the era of direct-acting antivirals. AB - BACKGROUND: The availability of novel direct-acting antivirals (DAAs) represents a new era of curative hepatitis C virus (HCV) treatment, with over 95% of patients infected with HCV genotype 1 achieving sustained virological response (SVR). Nevertheless, the majority of patients globally are unable to access these treatments because of cost and infrastructure constraints and, thus, remain untreated and uncured. DATA SOURCE: Relevant articles of peginterferon (PegIFN) based treatments in HCV and sofosbuvir-based treatments, simeprevir, daclatasvir/asunaprevir, ritonavir-boosted paritaprevir/ombitasvir/dasabuvir, and grazoprevir/elbasvir, were searched in PubMed database, including general population and special population. RESULTS: PegIFN in combination with ribavirin remains an important and relevant option for some patients, achieving SVR rates of up to 79% in genotype 1 and 89% in genotype 2 or 3 infections, which increases for patients with favorable IL28B genotypes. Triple therapy of DAA plus PegIFN/ribavirin is effective in treating difficult-to-cure patients infected with HCV genotype 3 or with resistance-associated variants. Owing to its long history in HCV management, the efficacy, tolerability and long-term outcomes associated with PegIFN alfa-2a are well established and have been validated in large-scale studies and in clinical practice for many populations. Furthermore, emerging data show that IFN-induced SVR is associated with lower incidences of hepatocellular carcinoma compared with DAAs. On the contrary, novel DAAs have yet to be studied in special populations, and long-term outcomes, particularly tumor development and recurrence in patients with cirrhosis and/or hepatocellular carcinoma, and reactivation of HBV in dually infected patients, are still unclear. CONCLUSION: In this interferon-free era, PegIFN-based regimens remain a safe and effective option for selected HCV patients. PMID- 28992879 TI - Surgical resection versus liver transplantation for hepatocellular carcinoma within the Hangzhou criteria: a preoperative nomogram-guided treatment strategy. AB - BACKGROUND: With the expansion of surgical criteria, the comparative efficacy between surgical resection (SR) and liver transplantation (LT) for hepatocellular carcinoma is inconclusive. This study aimed to develop a prognostic nomogram for predicting recurrence-free survival of hepatocellular carcinoma patients after resection and explored the possibility of using nomogram as treatment algorithm reference. METHODS: From 2003 to 2012, 310 hepatocellular carcinoma patients within Hangzhou criteria undergoing resection or liver transplantation were included. Total tumor volume, albumin level, HBV DNA copies and portal hypertension were included for constructing the nomogram. The resection patients were stratified into low- and high-risk groups by the median nomogram score of 116. Independent risk factors were identified and a visually orientated nomogram was constructed using a Cox proportional hazards model to predict the recurrence risk for SR patients. RESULTS: The low-risk SR group had better outcomes compared with the high-risk SR group (3-year recurrence-free survival rate, 71.1% vs 35.9%; 3-year overall survival rate, 89.8% vs 78.9%, both P<0.001). The high-risk SR group was associated with a worse recurrence-free survival rate but similar overall survival rate compared with the transplantation group (3-year recurrence free survival rate, 35.9% vs 74.1%, P<0.001; 3-year overall survival rate, 78.9% vs 79.6%, P>0.05). CONCLUSIONS: This nomogram offers individualized recurrence risk evaluation for hepatocellular carcinoma patients within Hangzhou criteria receiving resection. Transplantation should be considered the first-line treatment for high-risk patients. PMID- 28992880 TI - Delayed introduction of immunosuppressive regimens in critically ill patients after liver transplantation. AB - BACKGROUND: The manipulation of immunosuppression therapy remains challenging in patients who develop infectious diseases or multiple organ dysfunction after liver transplantation. We evaluated the outcomes of delayed introduction of immunosuppression in the patients after liver transplantation under immune monitoring with ImmuKnow assay. METHODS: From March 2009 to February 2014, 225 consecutive liver recipients in our institute were included. The delayed administration of immunosuppressive regimens was attempted in 11 liver recipients with multiple severe comorbidities. RESULTS: The median duration of non immunosuppression was 12 days (range 5-58). Due to the infectious complications, the serial ImmuKnow assay showed a significantly low ATP level of 64+/-35 ng/mL in the early period after transplantation. With the development of comorbidities, the ImmuKnow value significantly increased. However, the acute allograft rejection developed when a continuous distinct elevation of both ATP and glutamyltranspeptidase levels was detected. The average ATP level measured just before the development of acute rejection was 271+/-115 ng/mL. CONCLUSIONS: The delayed introduction of immunosuppressive regimens is safe and effective in management of critically ill patients after liver transplantation. The serial ImmuKnow assay could provide a reliable depiction of the dynamics of functional immunity throughout the clinical course of a given patient. PMID- 28992881 TI - Cost-effectiveness analysis of transcatheter arterial chemoembolization with or without sorafenib for the treatment of unresectable hepatocellular carcinoma. AB - BACKGROUND: Transcatheter arterial chemoembolization (TACE) and TACE in combination with sorafenib (TACE-sorafenib) have shown a significant survival benefit for the treatment of unresectable hepatocellular carcinoma (HCC). Adopting either as a first-line therapy carries major cost and resource implications. The objective of this study was to estimate the relative cost effectiveness of TACE against TACE-sorafenib for unresectable HCC using a decision analytic model. METHODS: A Markov cohort model was developed to compare TACE and TACE-sorafenib. Transition probabilities and utilities were obtained from systematic literature reviews, and costs were obtained from West China Hospital, Sichuan University, China. Survival benefits were reported in quality adjusted life-years (QALYs). The incremental cost-effectiveness ratio (ICER) was calculated. Sensitive analysis was performed by varying potentially modifiable parameters of the model. RESULTS: The base-case analysis showed that TACE cost $26 951 and yielded survival of 0.71 QALYs, and TACE-sorafenib cost $44 542 and yielded survival of 1.02 QALYs in the entire treatment. The ICER of TACE sorafenib versus TACE was $56 745 per QALY gained, which was above threshold for cost-effectiveness in China. Sensitivity analysis revealed that the major driver of ICER was the cost post TACE-sorafenib therapy with stable state. CONCLUSION: TACE is a more cost-effective strategy than TACE-sorafenib for the treatment of unresectable HCC. PMID- 28992882 TI - Bone metastases from hepatocellular carcinoma: clinical features and prognostic factors. AB - BACKGROUND: Bone metastases (BMs) from hepatocellular carcinoma (HCC) is an increasingly common disease in Asia. We assessed the clinical features, prognostic factors, and differences in outcomes related to BMs among patients with different treatments for HCC. METHODS: Forty-three consecutive patients who were diagnosed with BMs from HCC between January 2010 and December 2014 were retrospectively enrolled. The clinical features were identified, the impacts of prognostic factors on survival were statistically analyzed, and clinical data were compared. RESULTS: The median patient age was 54 years; 38 patients were male and 5 female. The most common site for BMs was the trunk (69.3%). BMs with extension to the soft tissue were found in 14 patients (32.5%). Most (90.7%) of the lesions were mixed osteolytic and osteoblastic, and most (69.8%) patients presented with multiple BMs. The median survival after BMs diagnosis was 11 months. In multivariate analyses, survival after BM diagnosis was correlated with Karnofsky performance status (P=0.008) and the Child-Pugh classification (P<0.001); BM-free survival was correlated with progression beyond the University of California San Francisco criteria (P<0.001) and treatment of primary tumors (P<0.001). BMs with extension to soft tissue were less common in liver transplantation patients. During metastasis, the control of intrahepatic tumors was improved in liver transplantation and hepatectomy patients, compared to conservatively treated patients. CONCLUSIONS: The independent prognostic factors of survival after diagnosis of BMs were the Karnofsky performance status and Child-Pugh classification. HCC patients developed BMs may also benefit from liver transplantation or hepatectomy. PMID- 28992883 TI - Comparative study of the effects of terlipressin versus splenectomy on liver regeneration after partial hepatectomy in rats. AB - BACKGROUND: Post-hepatectomy liver failure as a result of insufficient liver remnant is a feared complication in liver surgery. Efforts have been made to find new strategies to support liver regeneration. The aim of this study was to investigate the effects of terlipressin versus splenectomy on postoperative liver function and liver regeneration in rats undergoing 70% partial hepatectomy. METHODS: Seventy-two male Wistar rats were randomly assigned into three groups (n=24 in each group): 70% partial hepatectomy as control (PHC), 70% partial hepatectomy with splenectomy (PHS) or 70% partial hepatectomy with a micropump for terlipressin administration (PHT). Eight rats in each group were sacrificed on postoperative day (POD) 1, 3 and 7. To assess liver regeneration, immunohistochemical analysis of liver tissue using bromodeoxyuridine (BrdU) and Ki-67 labeling was performed. Portal venous pressure, serum concentrations of creatinine, urea, albumin, bilirubin and prothrombin time as well as liver-, body weight and their ratio were determined on POD 1, 3 and 7. RESULTS: The liver-, body-weight and their ratio were not statistically different among the groups. On POD 1, 3 and 7 portal venous pressure in the intervention groups (PHT: 8.13+/ 1.55, 10.38+/-1.30, 6.25+/-0.89 cmH2O and PHS: 7.50+/-0.93, 8.88+/-2.42, 5.75+/ 1.04 cmH2O) was lower compared to the control group (PHC: 8.63+/-2.06, 10.50+/ 2.45, 6.50+/-2.67 cmH2O). Hepatocyte proliferation in the intervention groups was delayed, especially after splenectomy on POD 1 (BrdU: PHS vs PHC, 20.85%+/-13.05% vs 28.11%+/-10.10%; Ki-67, 20.14%+/-14.10% vs 23.96%+/-11.69%). However, none of the differences were statistically significant. CONCLUSIONS: Neither the administration of terlipressin nor splenectomy improved liver regeneration after 70% partial hepatectomy in rats. Further studies assessing the regulation of portal venous pressure as well as extended hepatectomy animal models and liver function tests will help to further investigate mechanisms of liver regeneration. PMID- 28992885 TI - Helicobacter pylori and 17beta-estradiol induce human intrahepatic biliary epithelial cell abnormal proliferation and oxidative DNA damage. AB - BACKGROUND: Biliary cancers are more common in females, and previous studies have suggested that Helicobacter pylori (H. pylori) exists in the biliary system. However, the effects of H. pylori infection and estrogen on the biological behaviors of human biliary epithelium mucosa remain unknown. The present study aimed to clarify their effects on the proliferation, apoptosis, migration and oxidative DNA damage of a human intrahepatic biliary epithelial cell (HIBEC) line in vitro. METHODS: HIBECs were co-cultured with 17beta-estradiol (at 10-9 mol/L, 10-7 mol/L, and 10-5 mol/L) and H. pylori (at MOI=0.5:1, 1:1, and 2:1) and continuously passaged until the 15th generation (approximately 45 days). Then, the following assays were performed. HIBEC proliferation was measured using the CCK-8 assay, plate clone-formation assay and by determining Ki-67 expression with immunocytochemistry; cell apoptosis and migration were investigated using Annexin V/PI and transwell assays, respectively; and reactive oxygen species (ROS) and 8 hydroxy-2'-deoxyguanosine (8-OHdG) production were detected by flow cytometry and immunofluorescence staining combined with confocal laser scanning microscopy, respectively. The results were the basis for evaluating the level of oxidative stress and the related DNA damage in HIBECs. RESULTS: HIBECs maintained a normal morphology and vitality when treated with 17beta-estradiol (at 10-9 mol/L) and H. pylori (at MOI=0.5:1 and 1:1). 17beta-estradiol at 10-7 mol/L and 10-5 mol/L and H. pylori at MOI=2:1, by contrast, caused cell death. Compared with controls, HIBECs treated with 17beta-estradiol (10-9 mol/L) and H. pylori (MOI=1:1) had a higher up-regulation of proliferation, Ki-67 expression, clone formation, migration activity and the expression of ROS and 8-OHdG and exhibited a down regulation of apoptosis. The above effects were further increased when 17beta estradiol and H. pylori were combined (P<0.05). CONCLUSIONS: H. pylori and 17beta estradiol, separately or in combination, promoted cell proliferation and suppressed apoptosis of HIBECs in vitro. The above phenomena might be related to oxidative stress and its subsequent DNA damage with H. pylori and 17beta estradiol. PMID- 28992884 TI - Prospective comparison of prophylactic antibiotic use between intravenous moxifloxacin and ceftriaxone for high-risk patients with post-ERCP cholangitis. AB - BACKGROUND: The use of prophylactic antibiotics before endoscopic retrograde cholangiopancreatography (ERCP) is recommended by all major international gastroenterological societies, especially in the presence of an obstructed biliary system. This study compared the occurrence rate of post-procedural complications, including cholangitis and septicemia, between prophylactic intravenous moxifloxacin and ceftriaxone in patients with bile duct obstruction scheduled for therapeutic ERCP. METHODS: From November 2013 to July 2015, 86 consecutive patients with biliary obstruction with one or more factors predicting benefits of antibiotic prophylaxis prior to ERCP were included in the current randomized open-label non-inferiority trial (ClinicalTrial.gov identifier NCT02098486). Intravenous moxifloxacin (400 mg/day) or ceftriaxone (2 g/day) were given 90 minutes before ERCP, and were administered for more than 3 days if the patient developed symptoms and signs of cholangitis or septicemia. Recalcitrant cholangitis was defined as persistence of cholangitis for more than 5 days after ERCP or recurrence of cholangitis within 30 days after ERCP. RESULTS: Recalcitrant cholangitis occurred in 1 (2.3%) and 2 (4.8%) patients receiving intravenous moxifloxacin and ceftriaxone group, respectively (P=0.612). Septicemia was noted in 1 (2.3%) and 1 (2.4%) patient in intravenous moxifloxacin and ceftriaxone group, respectively (P=1.0). The mean hospital stay was also not significantly different between the moxifloxacin and ceftriaxone groups (8.8+/ 7.2 vs 9.1+/-9.4 days, P=0.867). Antibiotic resistance of the isolated pathogens by in vitro activity assay was noted in 1 (2.3%) and 2 (4.8%) patients in the moxifloxacin and ceftriaxone group, respectively (P=0.612). CONCLUSION: Intravenous moxifloxacin is not inferior to intravenous ceftriaxone for the prophylactic treatment of post-ERCP cholangitis and cholangitis-associated morbidity. PMID- 28992886 TI - Tailored pancreatic reconstruction after pancreaticoduodenectomy: a single-center experience of 892 cases. AB - BACKGROUND: Pancreatic reconstruction following pancreaticoduodenectomy (PD) is still debatable even for pancreatic surgeons. Ideally, pancreatic reconstruction after PD should reduce the risk of postoperative pancreatic fistula (POPF) and its severity if developed with preservation of both exocrine and endocrine pancreatic functions. It must be tailored to control the morbidity linked to the type of reconstruction. This study was to show the best type of pancreatic reconstruction according to the characters of pancreatic stump. METHODS: We studied all patients who underwent PD in our center from January 1993 to December 2015. Patients were categorized into three groups depending on the presence of risk factors of postoperative complications: low-risk group (absent risk factor), moderate-risk group (presence of one risk factor) and high-risk group (presence of two or more risk factors). RESULTS: A total of 892 patients underwent PD for resection of periampullary tumor. BMI >25 kg/m2, cirrhotic liver, soft pancreas, pancreatic duct diameter <3 mm, and pancreatic duct location from posterior edge <3 mm are risk variables for development of postoperative complications. POPF developed in 128 (14.3%) patients. Delayed gastric emptying occurred in 164 (18.4%) patients, biliary leakage developed in 65 (7.3%) and pancreatitis presented in 20 (2.2%). POPF in low-, moderate- and high-risk groups were 26 (8.3%), 65 (15.7%) and 37 (22.7%) patients, respectively. Postoperative morbidity and mortality were significantly lower with pancreaticogastrostomy (PG) in high risk group, while pancreaticojejunostomy (PJ) decreases incidence of postoperative steatorrhea in all groups. CONCLUSIONS: Selection of proper pancreatic reconstruction according to the risk factors of patients may reduce POPF and postoperative complications and mortality. PG is superior to PJ as regards short-term outcomes in high-risk group but PJ provides better pancreatic function in all groups and therefore, PJ is superior in low- and moderate-risk groups. PMID- 28992887 TI - Risk factors and managements of hemorrhage associated with pancreatic fistula after pancreaticoduodenectomy. AB - BACKGROUND: Post-pancreaticoduodenectomy pancreatic fistula associated hemorrhage (PPFH) is one of the leading lethal complications. Our study was to analyze the risk factors and managements of hemorrhage associated with pancreatic fistula after pancreaticoduodenectomy, and to evaluate treatment options. METHOD: We analyzed 445 patients who underwent pancreaticoduodenectomy or pylorus-preserving pancreaticoduodenectomy and evaluated the relevance between clinical data and PPFH. RESULTS: The incidence of postoperative pancreatic fistula (POPF) was 27.42% (122/445), and the incidence of PPFH was 4.49% (20/445). Among the 20 patients with PPFH, 7 died and 13 were cured. Interventional angiographic therapy was performed for 10 patients and 5 were successfully treated. Relaparotomy was performed for 5 patients and 2 were successfully cured. Univariate logistic regression analysis indicated that several risk factors were related to PPFH: the nature of tumor (carcinoid/low-grade or high-grade malignancy), preoperative day 1 serum prealbumin, preoperative day 1 total bilirubin (TBIL), operative time, blood loss in the operation, operative method (vascular resection and revascularization), postoperative day 3 TBIL, biliary fistula, and the grade of POPF. The multivariate stepwise logistic regression analysis demonstrated that the nature of tumor and the grade of POPF were independently risk factors of PPFH. Receiver operating characteristic curve indicated that preoperative day 1 serum prealbumin level <173 mg/L and postoperative day 3 TBIL level >=168 umol/L were the risk factors of PPFH. CONCLUSIONS: The risk of PPFH was found to be increased with high potential malignancy and high grade of POPF. Angiography embolization is one of the major and effective therapies for PPFH. Extraluminal intraluminal PPFH is more serious and needs more aggressive treatments. PMID- 28992888 TI - The "Colonial Wig" pancreaticojejunostomy: zero leaks with a novel technique for reconstruction after pancreaticoduodenectomy. AB - BACKGROUND: Postoperative pancreatic fistula (POPF) remains common and morbid after pancreaticoduodenectomy (PD). A major advance in the study of POPF is the fistula risk score (FRS). METHODS: We analyzed 48 consecutive patients undergoing PD. The "Colonial Wig" pancreaticojejunostomy (CWPJ) technique was used in the last 22 PDs, we compared 22 CWPJ to 26 conventional PDs. RESULTS: Postoperative morbidity was 49% (27% Clavien grade >2). The median length of hospital stay was 11 days. In the first 26 PDs, the PJ was performed according to standard techniques and the clinically relevant POPF (CR-POPF) rate was 15%, similar to the FRS-predicted rate (14%). In the next 22 PJs, the CWPJ was employed. Although the FRS-predicted rates were similar in these two groups (14% vs 13%), the CR POPF rate in the CWPJ group was 0 (P=0.052). CONCLUSION: Early experience with the CWPJ is encouraging, and this anastomosis may be a safe and effective way to lower POPF rates. PMID- 28992889 TI - Polymorphic multiple hepatocellular adenoma including a non-steatotic HNF1alpha inactivated variant. PMID- 28992890 TI - Gastrointestinal tract post-transplant lymphoproliferative disorder after liver transplantation. PMID- 28992891 TI - Patterns of medical utilization before the first hospitalization for women with anorexia nervosa in Taiwan. AB - OBJECTIVE: The aim of this paper was to analyze medical utilization patterns of female patients with anorexia nervosa before their first inpatient care visit for anorexia nervosa using the National Health Insurance Research Database (NHIRD) of Taiwan. METHOD: We selected female anorexia nervosa patients (n=239) and control participants hospitalized for peptic ulcers (n=478) or appendectomy (n=478) who were matched by age and incident year from two subsets of the NHIRD. The number of visits, specialists, diagnosis distribution, and selected procedures used in ambulatory services during the 2-year period before the index admission were identified and compared. Healthcare service expenditures were also analyzed. RESULTS: Compared to the control groups, the female anorexia nervosa patients used more outpatient services (anorexia nervosa, 58.6+/-45.0 visits; peptic ulcers, 45.3+/-37.3 visits; appendectomy, 32.5+/-26.0 visits), mainly due to psychiatric visits. Anorexia nervosa patients were more likely to have received a diagnosis of digestive, endocrine/metabolic, and mental disorders than patients in the control groups. Although nearly equal percentages of patients in the three groups had obtained a diagnosis of a digestive disease, anorexia nervosa patients received digestive disease diagnoses with greater frequency. CONCLUSIONS: We posit that the various physical symptoms of anorexia nervosa patients and physicians' low level of suspicion of anorexia nervosa led to delayed diagnoses and greater medical utilization than that of the controls groups. Education to raise awareness of anorexia nervosa and other eating disorders among physicians is warranted. PMID- 28992892 TI - Obstetric risk factors for depression during the postpartum period in South Korea: a nationwide study. AB - OBJECTIVE: Postpartum depression is related to many adverse effects in both mothers and their children; therefore, proper screening and early interventions are needed. This study aims to identify the risk factors of postpartum depression. Our primary focus is on obstetric risk factors. METHODS: This study is a cross-sectional study which we extracted the data of women who gave birth between January 1st, 2010 and December 31st, 2012 from the Health Insurance Review and Assessment service (HIRA) database. We analyzed the data using multivariable logistic regression models. RESULTS: A total of 17,483 (1.4%) women suffered from depression during the postpartum period. Younger (<20years) and advanced maternal age (>=35years), primiparity, previous depression, peripartum hysterectomy, uterine artery embolization, preterm delivery, placental abruption, cesarean delivery, induced labor, and preeclampsia were found to increase the likelihood of having depression after delivery. CONCLUSIONS: Our findings suggest that there are several risk factors that lead women to postpartum depression. Therefore, early detection and well-management of the symptoms and risk factors for postpartum depression along with social support can help both physical and psychological conditions of women after childbirth. PMID- 28992893 TI - Translation and validation of the Dutch version of the Fear of Cancer Recurrence Inventory (FCRI-NL). AB - OBJECTIVE: The study objectives are to translate the FCRI in Dutch, and to explore the factor structure and the psychometric qualities of the Dutch translation of the Fear of Cancer Recurrence Inventory (FCRI-NL). METHOD: The original French-Canadian FCRI had been forward-backward translated into English by the developers, and this method was also used to translate the English version of the FCRI into Dutch. Patients were recruited via patient organizations between July 2011 and October 2013. To replicate the original 7-factor structure of the FCRI, confirmatory factor analysis (CFA) was performed. To examine the psychometric qualities, reliability (Cronbach's alpha), test-retest reliability (intra-class correlations; ICC), and convergent and divergent validity (Spearman's correlations) were calculated. RESULTS: From 290 cancer patients, 255 (88%) were eligible for analysis (aged 51.0+/-9.8years, 88.6% women). CFA showed a reasonable yet suboptimal fit of the hypothesized model to the data. The FCRI NL has good reliability (Cronbach's alpha=0.93 for the total scale and alpha=0.75 0.92 for the subscales) and test-retest reliability (ICC=0.84 for the total scale and ICC=0.56-0.87 for the subscales). Convergent (r=0.53-0.66 for the FCRI-NL and r=0.48-0.57 for the FCRI-SF-NL) and divergent (r=-0.20--0.07 for the FCRI-NL and r=-0.28--0.17 for the FCRI-SF-NL) validity was demonstrated. CONCLUSION: The FCRI NL seems to have sufficient psychometric properties. However, the FCRI-NL total score should be interpreted with caution. The Severity subscale (FCRI-SF-NL) may be a valuable screening tool for fear of cancer recurrence severity in clinical care. PMID- 28992894 TI - Chronic prostatitis and comorbid non-urological overlapping pain conditions: A co twin control study. AB - OBJECTIVES: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is characterized by pain and voiding symptoms in the absence of an obvious infection or other cause. CP/CPPS frequently occurs with non-urological chronic overlapping pain conditions (COPCs) of unknown etiology. We conducted a co-twin control study in men discordant for chronic prostatitis (CP), an overarching diagnosis of which approximately 90% is CP/CPPS. The primary aim was to investigate the contribution of familial factors, including shared genetic and common environmental factors, to the comorbidity of CP and COPCs. METHODS: Data from 6824 male twins in the Vietnam Era Twin Registry were examined to evaluate the association between self reported lifetime physician diagnosis of CP with COPCs including fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, temporomandibular disorder, tension headaches, and migraine headaches. Random effects logistic regression models were used and within-pair analyses evaluated confounding effects of familial factors on the associations. RESULTS: There were significant associations between CP and all 6 examined COPCs. After adjusting for shared familial influences in within twin pair analyses, the associations for all COPCs diminished but remained significant. Familial confounding was strongest for the association of CP with fibromyalgia and temporomandibular disorder and smallest for irritable bowel syndrome. CONCLUSIONS: CP and COPCs are highly comorbid. These associations can be partially explained by familial factors. The mechanisms underlying these relationships are likely diverse and multifactorial. Future longitudinal research can help to further elucidate specific genetic and environmental mechanisms and determine potentially causal relationships between CP and its comorbidities. PMID- 28992895 TI - Body-scaled action in obesity during locomotion: Insights on the nature and extent of body representation disturbances. AB - OBJECTIVE: Conscious perception of our own body, also known as body image, can influence body-scaled actions. Certain conditions such as obesity are frequently accompanied by a negative body image, leaving open the question if body-scaled actions are distorted in these individuals. METHODS: To shed light on this issue, we asked individuals affected by obesity to process dimensions of their own body in a real action: they walked in a straight-ahead direction, while avoiding collision with obstacles represented by door-like openings that varied in width. RESULTS: Participants affected by obesity showed a body rotation behavior similar to that of the healthy weighted, but differences emerged in parameters such as step length and velocity. CONCLUSION: When participants with obesity walk through door-like openings, their body parts rotation is scaled according to their physical body dimensions; however, they might try to minimize risk of collision. Our study is in line with the hypothesis that unconscious body-scaled actions are related to emotional, cognitive and perceptual components of a negative body image. PMID- 28992896 TI - Psychological stress as a measure for treatment response prediction in idiopathic sudden hearing loss. AB - OBJECTIVE: Early prediction of therapeutic outcomes could reduce exposure to ineffective treatments and optimize clinical outcomes. However, none of the known otologic predictors is amenable to therapeutic intervention for idiopathic sudden sensorineural hearing loss (ISSNHL). The aims of this study were to investigate psychological stress as a potential predictor to discriminate outcomes in ISSNHL. METHODS: Various psychological measures were conducted including structured interview assessment tools in patients with recently diagnosed ISSNHL before initiating treatment. Using logistic regression analysis, we identified the predictors of treatment response and estimated the probability of treatment response in 50 ISSNHL patients who participated in a clinical trial. RESULTS: Treatment non-responders were significantly differentiated from responders by various psychological problems. The depression subscore of Modified form of Stress Response Inventory (SRI-MF) (p=0.007) and duration of hearing loss (p=0.045) significantly predicted treatment response after controlling other clinical correlates. The same predictors were identified from different treatment response measured using Siegel's criteria. The most discriminative measure for treatment response was SRI-MF depression score with an overall classification accuracy of 73%. CONCLUSIONS: We found depressive stress response to be the strong predictor of treatment response in patients with ISSNHL. Our results highlight the potential use of the psychiatric approach as a tool for enhancing therapeutic outcomes. Future stress intervention studies with larger number of ISSNHL patients are needed. PMID- 28992897 TI - Inflammatory Bowel Disease and Eating Disorders: A systematized review of comorbidity. AB - OBJECTIVE: Research has shown that there is an association between Inflammatory Bowel Disease, anxiety and mood disorders, however little is known about their association with Eating Disorders. In this paper we will present a case of a young female with a comorbid diagnosis of Inflammatory Bowel Disease and Eating Disorder, and then discuss the results from a systematic review of the literature, describing published cases of patients with the same condition. METHODS: A systematized review of the literature was conducted according to MOOSE guidelines. A computerized literature search of MEDLINE, PsycINFO and EMBASE, and a manual search through reference lists of selected original articles were performed to identify all published case-reports, case series and studies of Inflammatory Bowel Disease and Eating Disorders. RESULTS: Fourteen articles were included, encompassing 219 cases, including ours. The vast majority were females ranging from 10 to 44years old. Anorexia Nervosa (n=156) and Crohn's Disease (n=129) was the most frequent combination (n=90) reported in the literature. These cases present a poor prognosis because of corticoid refusal, medication abandon and/or deliberate exacerbation of IBD symptoms, in the context of trying to lose weight. CONCLUSION: Recent evidence suggests there is a possible association between Inflammatory Bowel Disease and Eating Disorders, although the mechanisms involved in its ethiopathogenesis are still unknown. To be aware of this association is important because a delayed diagnosis of this comorbidity may lead to worse prognosis. Further research and a multidisciplinary approach could facilitate earlier diagnosis and provide therapeutic interventions. PMID- 28992898 TI - The trait and occasion components of fatigue and their association with sickness absence. AB - OBJECTIVE: Fatigue is an important health outcome in public and occupational health care. To correctly understand and treat high levels of (prolonged) fatigue it is important to disentangle the state of fatigue into a time-varying (occasion) and -invarying (trait) component. Not only for understanding of the construct itself over time but also for its relation with (health) outcomes such as sickness absence. METHODS: Longitudinal data (n=2316) from the Maastricht Cohort Study (MCS) study was used, which assessed fatigue across 4-month intervals using the Checklist Individual Strength (CIS). RESULTS: It was found that the occasion component explains 27.60% (95%-CI [25.80%; 29.40%]) of the variance of fatigue and the trait component 71.00% (95%-CI [69.00%; 72.90%]). The trait component was, furthermore, found to be a significant predictor of sickness absence. CONCLUSION: Fatigue has a considerable time-invariant component. As this component is also related with other adverse health outcomes, preventive measures and interventions should take the difference between the occasion and trait component of fatigue into account. PMID- 28992899 TI - Tailored online cognitive behavioural therapy with or without therapist support calls to target psychological distress in adults receiving haemodialysis: A feasibility randomised controlled trial. AB - BACKGROUND: Psychological distress is prevalent in haemodialysis (HD) patients yet access to psychotherapy remains limited. This study assessed the feasibility and acceptability of online cognitive-behavioural therapy (CBT) tailored for HD patients, with or without therapist support, for managing psychological distress. METHODS: This feasibility randomised controlled trial recruited patients from a UK HD centre. Following psychological distress screens, patients with mild moderate psychological distress (Patient Health Questionnaire PHQ-9; score: 5-19 and/or Generalised Anxiety Disorder; GAD-7 score: 5-14) who met remaining inclusion criteria were approached for consent. Consenters were individually randomised (1:1) to online-CBT or online-CBT plus three therapist support calls. Outcomes included recruitment, retention, and adherence rates. Exploratory change analyses were performed for: psychological distress, quality of life (QoL), illness perceptions, and costs. The statistician was blinded to allocation. RESULTS: 182 (44%) out of 410 patients approached completed psychological distress screens. 26% found screening unacceptable; a further 30% found it unfeasible. Psychological distress was detected in 101 (55%) patients, 60 of these met remaining inclusion criteria. The primary reason for ineligibility was poor computer literacy (N=17, 53%). Twenty-five patients were randomised to the supported (N=18) or unsupported arm (N=7); 92% were retained at follow-up. No differences in psychological distress or cost-effectiveness were observed. No trial adverse events occurred. CONCLUSION: Online CBT appears feasible but only for computer literate patients who identify with the label psychological distress. A definitive trial using the current methods for psychological distress screening and online care delivery is unfeasible. ClinicalTrials.gov Identifier: NCT02352870. PMID- 28992900 TI - Cultural differences in symptom representation for depression and somatization measured by the PHQ between Vietnamese and German psychiatric outpatients. AB - OBJECTIVE: Despite an extensive body of research on somatic symptom presentation among people of East- and Southeast-Asian descent, results are still inconclusive. Examining and comparing symptom presentation in clinically and ethnically well-characterized populations may constitute a step towards understanding symptom presentation between patients with a different cultural background. This study aims to compare Vietnamese and German patients regarding cultural dynamics of symptom presentation upon first admission to a psychiatric outpatient service. METHODS: 110 Vietnamese and 109 German patients seeking psychiatric treatment at two outpatient clinics completed the Patient Health Questionnaire (PHQ). The somatic symptom subscale (PHQ-15), the depression subscale (PHQ-9) and PHQ-subscales examining anxiety and psychosocial stress levels were analyzed and compared for both groups using multivariate analysis of covariance. Regression analysis was utilized to examine the influences of sociodemographic and migration specific factors. RESULTS: Vietnamese and German patients showed comparable Cronbach's alpha for all subscales. Vietnamese patients endorsed significantly higher levels of somatic symptoms overall and on certain items (as pain-related items, dizziness, and fainting spells) despite similar levels of depression severity in comparison with German patients. Vietnamese patients with poor German language skills showed a significantly higher focus on somatic symptoms. CONCLUSION: Raising awareness for cultural dynamics of symptom presentation in patients with depression is indispensable. Cross-cultural symptom assessment using the PHQ seems feasible and expands our understanding of depressive and psychosomatic symptoms when assessed by clinicians. PMID- 28992902 TI - Lynn Margulis and the origin of the eukaryotes. PMID- 28992901 TI - Prenatal stress perception and coping strategies: Insights from a longitudinal prospective pregnancy cohort. AB - OBJECTIVE: Prenatal distress has been linked to pregnancy complications and poor offspring's health, despite the fact that longitudinal assessments of various stress dimensions are still lacking. Hence, we aimed to assess perceived stress over the course of pregnancy. Moreover, we examined whether social support and coping styles are linked to prenatal stress trajectories. METHODS: Data from 543 women participating in the PRINCE (Prenatal Identification of Children Health) study, a prospective population-based cohort study, was used for the present analyses. Once per trimester the women completed questionnaires regarding different psychometric measures, including the Perceived Stress Scale (PSS). Linear mixed regression models were used to examine perceived stress development longitudinally and to relate social support and coping styles to stress trajectories during pregnancy. RESULTS: A significant decrease of perceived stress was observed over the course of pregnancy. Stratifying the study sample according to parity, women delivering their first child had continuously lower perceived stress scores compared to women having already one or more children, and a significant decrease during pregnancy was exclusively observed in primiparous women. Both, positive coping strategies and higher perceived and received social support were independently associated with lower perceived stress, while evasive coping strategies were associated with higher levels of perceived stress. CONCLUSION: Our study reveals stress perception trajectories during pregnancies in primi- and multiparous women. Our findings underscore the need for intervention strategies aiming to improve social support and positive coping strategies especially in multiparous women in order to reduce the risks for adverse pregnancy outcomes. PMID- 28992903 TI - Use of Purina Pro Plan Veterinary Diet UR Urinary St/Ox to Dissolve Struvite Cystoliths. AB - The objective of this study was to determine the efficacy of feeding the commercially available diet, Purina Pro Plan Veterinary Diets UR Urinary St/Ox, for the dissolution of struvite cystoliths in cats with naturally occurring disease. Twelve cats with clinical signs of lower urinary tract disease and cystoliths confirmed via radiographs were enrolled. The cats were fed the study diet ad libitum and assessed by abdominal radiographs weekly. Cats with cystoliths that resolved based on radiographs and confirmatory ultrasound examination were considered diet successes. Cats with no change in cystolith size after 2-6 weeks underwent cystotomy for stone removal, aerobic culture and antimicrobial susceptibility testing, and analysis. All cats accepted the study diet, and weight loss was not noted over the course of the study. Total cystolith dissolution was achieved by week 2 for 5 cats, which were presumed to have struvite cystoliths. All other cats underwent cystotomy for stone removal after radiographic evidence of cystoliths were still present at 2 weeks (1 cat with severe signs), 4 weeks (5 cats), or 6 weeks (1 cat). The cystoliths that were surgically removed were calcium oxalate (5 cats) and mixed (2 cats) and would not be expected to dissolve with this diet. Follow-up radiographs from 6 cats fed the diet long term (3 presumed struvite and 3 with other cystoliths removed surgically) were collected from 1 to 6 months after beginning the study and showed no evidence of cystolith recurrence. While larger case numbers are needed, these results suggest that feeding Purina Pro Plan Veterinary Diets UR Urinary St/Ox can successfully dissolve cystoliths that are likely struvite and may lessen the risk of recurrence of struvite and calcium oxalate cystoliths. PMID- 28992904 TI - Submucosal Collagen Injection for Management of Urinary Incontinence Following Urethral Stent Placement. AB - An 8-year-old, entire, male British Bulldog was referred for a week-long history of severe stranguria and dysuria. A prostatic wash was diagnostic of prostatic carcinoma. A transluminal urethral stent was placed in the proximal urethra, which resulted in resolution of the urinary obstruction, however, the dog developed severe urinary incontinence after the procedure. Cystoscopically-guided submucosal collagen injections were performed immediately proximal to the os penis. The dog's incontinence resolved with a single collagen injection for the 10-month follow-up period. PMID- 28992905 TI - Perioperative Occlusion of a Subcutaneous Ureteral Bypass Secondary to a Severe Pyonephrosis in a Birman Cat. AB - A subcutaneous ureteral bypass (SUB) was placed in a 10-year-old Birman cat for management of unilateral ureterolithiasis. Perioperative occlusion of the nephrostomy tube of the SUB device happened secondary to a severe pyonephrosis. Flushing of the system throught the subcutaneous shunting port was made with saline solution after clamping the urinary bladder catheter. Repetitive flushing of the device was performed daily for 3 days to be sure of the remanent patency of the catheter. Repetitive flushing of the SUB device is a successful renal sparing treatment for pyonephrosis in a cat and may be considered as an effective treatment option for this condition. PMID- 28992906 TI - Renal Amyloidosis Associated With Kartagener Syndrome in a Dog. AB - A 4-year-old cocker spaniel, male, of 12kg body weight was presented because of the onset of polyuria or polydipsia. From the first months of its life, the dog had exhibited constant serous to mucopurulent nasal discharge, productive cough, sneezing, reverse sneezing, otitis, and recurrent episodes of fever. The respiratory signs had been treated several times with antibiotics, without ever achieving a complete resolution. Clinical examination revealed normal rectal temperature (38.3 degrees C), increased respiratory rate (40breaths/min), a copious mucous nasal discharge and right deviation of the heart apex beat (ictus cordis). Increased respiratory sounds with moist rales and crackles were found on chest auscultation. An increase in serum creatinine, urea and phosphorus, hypoalbuminemia and proteinuria were found. Lateral and ventrodorsal radiographs of the thorax and of the abdomen showed the transposition of the heart, with the cardiac apex pointing toward the right (dextrocardia), bronchointerstitial lung pattern, areas of consolidation, lesions consistent with bronchiectasis caves and a mirror-image of abdominal organs, confirming the diagnosis of complete situs inversus (CSI). Respiratory signs, combined with CSI, suggested the diagnosis of Kartagener syndrome (KS). Abdominal ultrasound showed an increase in the echogenicity of the renal parenchyma, a loss of definition of the corticomedullary line, slight bilateral pyelectasis, and decreased cortical perfusion. The dog died 2 months later because of a further worsening of the clinical condition. Necroscopy demonstrated the existence of CSI, rhinosinusitis, bronchitis, and bronchiectasis, so confirming the diagnosis of KS, and renal amyloidosis. This is the first case reported in veterinary medicine of the presence of renal amyloidosis together with KS in a dog. PMID- 28992907 TI - Scaling Relationships Among Heart Rate, Electrocardiography Parameters, and Body Weight. AB - Although heart rate (HR) is one of the most important clinical parameters determined via physical examinations, little information is available on the normal HR in dogs, which may be related to the high variability of body weight (BW) in this species. HR is determined by the discharge rate of the sinus node, which is dependent on the autonomic nervous system and the release of catecholamines. The allometric relationship between BW and HR in different species has been described as inversely proportional; however, this relationship has been refuted. Certain authors have reported that the relationship between HR and BW in dogs is based on temperament as well as sympathetic autonomic stimulation of the sinus node in small breeds compared with large breeds. The aim of this study was to analyze the effects of weight, sex, age and temperament on the HR, heart rate variability and serum catecholamine (epinephrine and norepinephrine) levels in dogs. We evaluated 48 adult dogs of both sexes and various breeds and ages and divided the dogs into 5 BW groups: <5kg (n = 8), 5 10kg (n = 10), 10-25kg (n = 10), 25-45kg (n = 10), and >45kg (n = 10). The measured parameters were HR, breath rate (BR) and body temperature. We also performed an ambulatory electrocardiogram and electrocardiography (ECG) test for 24 hours (Holter monitor) and determined the serum levels of the catecholamines epinephrine and norepinephrine. We observed correlations between HR and sex; differences among the weight groups with respect to ECG variables and epinephrine levels; and differences among the temperament categories for certain clinical parameters, such as HR and BR. Age affected the R wave amplitude, and an allometric relationship was not observed between HR and BW in the dogs. Our results indicated that weight was associated with variations in the ECG variables; age and sex were associated with variations in HR; and temperament had a significant influence on the HR and BR of the dogs. PMID- 28992908 TI - Evaluation of Pericardial Effusion in Dogs and Successful Treatment Using a Hemodialysis Fistula Needle: A Retrospective Study. AB - The aim of this retrospective study was to assess epidemiology and echocardiographic findings of pericardial effusion in canine patients and to determine the clinical usefulness and safety of a new pericardiocentesis technique, using a "fistula needle" for hemodialysis. A database of 5304 dogs of different breeds, age, gender, type, and severity of the cardiac disease, referred for a specialist cardiology and echocardiographic examination from 2009 2016, was reviewed. All the dogs were subjected to echocardiography; when possible and required, an echo-guided pericardiocentesis was performed by mean of a 17G "fistula needle" commonly used for hemodialysis. Complete echocardiography was repeated at the end of each pericardiocentesis. Pericardial effusion was identified by echocardiography in 91 dogs (1.71%), 20 were female (21.98%) and 71 were male (78.02%). PE caused cardiac tamponade in 38/91 cases (41.76%). A clear evidence of a neoplasm was found in 33 cases (36.26%). In 32 cases (35.16%) severe degenerative mitral and tricuspid valve disease was detected as the cause of the pericardial effusion. Echo-guided pericardiocentesis was performed in 28 cases (30.77%) with cardiac tamponade. No adverse effects were found in any of the patients during the 48 hours of follow up after pericardiocentesis. This study showed the high incidence of pericardial effusion due to severe bilateral degenerative valve disease in adult to elderly dogs of different breeds. Moreover, the use of a "fistula needle" for pericardiocentesis in dogs showed no adverse effects. PMID- 28992909 TI - Aberrant Left Subclavian Artery in a Beagle Puppy With a Persistent Right Aortic Arch. Use of Cone Beam Computed Tomography to Diagnose a Vascular Ring Anomaly. AB - A 7-week-old, 1.045kg female beagle dog was referred to investigate a supposed vascular ring anomaly. Cone beam computed tomography with contrast enhanced arterial phase accomplished by a rapid manual intravenous injection of iodinated agent during the scanning process revealed a persistent right aortic arch and an aberrant left subclavian artery that compressed dorsally the esophagus in the cranial mediastinum. Third left intercostal thoracotomy was performed to transect the left subclavian artery. This is the first description of a vascular ring anomaly that was diagnosed with a cone beam computed tomography in veterinary medicine. PMID- 28992910 TI - Extreme Tetralogy of Fallot With Polycythemia in a Ferret (Mustela putorius furo). AB - A 5-month-old, intact male ferret (Mustela putorius furo) was presented with apathy, tachypnea and exercise intolerance. On initial physical examination, tachypnea and cyanosis were the two primary clinical signs detected. The complete blood count also revealed a severe polycythemia, with lymphopenia, neutrophilia and eosinophilia. Further diagnostic imaging tests were performed. The thoracic radiographs revealed cardiomegaly and a diffuse alveolar pulmonary pattern. Consequently, an echocardiography was performed and showed an interventricular septal defect, pulmonic artery occlusion, overriding of the aorta and right ventricle hypertrophy. All abnormalities were compatible with a tetralogy of Fallot (TOF). As a treatment plan, a phlebotomy was performed and the ferret was posteriorly maintained with oxygen and fluid therapy. The following day, the hematocrit decreased 11% and the respiratory distress improved. Four days later, the ferret got clinically worse and was euthanized. A necropsy was performed and confirmed the presence of an extreme TOF with a diffused interstitial pneumonia secondary to Pneumocystis carinii. To the author's knowledge, this is the first report of an extreme tetralogy of Fallot with polycythemia in a ferret. PMID- 28992911 TI - Whole-Body Vibration Exercise on Hematology and Serum Biochemistry in Healthy Dogs. AB - The present study aimed to evaluate the influence of whole-body vibration (WBV) exercise on hematology and serum biochemistry in healthy dogs. Ten intact beagle dogs, 3 females, and 7 males, with a mean age of 3 years, and mean body mass of 14.3kg, body condition score between 4.0/9 and 4.5/9 were evaluated. The WBV sessions were done with the dog standing up on all 4 feet on a vibrating platform. Daily session of 30Hz for 5 minutes, followed by 50Hz for 5 minutes and finishing with 30Hz for 5 minutes was accomplished for 5 days. The velocity and amplitude of the vibrating platform were 12-40m/s2 and 1.7-2.5mm, respectively. Blood samples were collected, before and immediately after the WBV platform exercise session, and 1 and 6 hours after the end of each session for 5 days. In addition, blood samples were collected 24 hours and 48 hours after the last WBV platform exercise session. Complete blood count and serum biochemistry (alanine aminotransferase, aspartate aminotransferase, creatine kinase, blood urea nitrogen, creatinine, and serum total protein) were the data analyzed. The erythrocytes, hemoglobin, and packet cell volume values decreased, whereas the leukocytes, neutrophils, and eosinophils values increased after WBV platform exercise sessions; however, all values were within the reference range. Other hematological and serum biochemical parameters did not show important variations. In conclusion, the WBV exercise sessions attended for 5 consecutive days did not adversely affect the hematology and serum biochemistry of adult healthy dogs. PMID- 28992912 TI - Voluntary monitoring systems for pig health and welfare in the UK: Comparative analysis of prevalence and temporal patterns of selected non-respiratory post mortem conditions. AB - Collection of abattoir data related to public health is common worldwide. Standardised on-going programmes that collect information from abattoirs that inform producers about the presence and frequency of disease that are important to them rather than public health hazards are less common. The three voluntary pig health schemes, implemented in the United Kingdom, are integrated systems which capture information on different macroscopic disease conditions detected in slaughtered pigs. Many of these conditions have been associated with a reduction in performance traits and consequent increases in production costs. The schemes are the Wholesome Pigs Scotland in Scotland, the British Pig Health Scheme in England and Wales and the Pig Regen Ltd. health and welfare checks in Northern Ireland. In this study, four post mortem conditions (pericarditis, milk spots, papular dermatitis and tail damage) were surveyed and analysed over a ten and half year period, with the aim to compare the prevalence, monthly variations, and yearly trends between schemes. Liver milk spot was the most frequently recorded condition while tail damage was the least frequently observed condition. The prevalence of papular dermatitis was relatively low compared to liver milk spot and pericarditis in the three schemes. A general decreasing trend was observed for milk spots and papular dermatitis for all three schemes. The prevalence of pericarditis increased in Northern Ireland and England and Wales; while Scotland in recent years showed a decreasing trend. An increasing trend of tail damage was depicted in Scotland and Northern Ireland until 2013/2014 followed by a decline in recent years compared to that of England and Wales with a decreasing trend over the full study period. Monthly effects were more evident for milk spots and papular dermatitis. Similarity of the modus operandi of the schemes made the comparison of temporal variations and patterns in gross pathology between countries possible over time, especially between countries with similar pig production profile. This study of temporal patterns enables early detection of prevalence increases and alerts industry and researchers to investigate the reasons behind such changes. These schemes are, therefore, valuable assets for endemic disease surveillance, early warning for emerging disease and also for monitoring of welfare outcomes. PMID- 28992913 TI - Reliability of techniques used in the diagnosis of canine visceral leishmaniasis by the national control program in Brazil: A survey in an area of recent transmission. AB - One of the key components of the Brazilian Program for the Control of Visceral Leishmaniasis (PCLV) is the euthanasia of Leishmania-infected canine reservoirs, the detection of which depends on a screening procedure involving a Dual Path Platform(r) (DPP) immunoassay and a confirmatory enzyme-linked immunosorbent assay (ELISA). The aims of the present study were to evaluate the reliability of these techniques in a region of recent transmission of canine VL, to follow up the seroconversion 3-4 months after the initial diagnosis of DPP reactive but ELISA indeterminate or non-reactive dogs, and to identify the species of Leishmania in circulation in the area. Each animal was submitted to DPP under field conditions, performed by municipal health workers using peripheral blood (DPP-field), to DPP under laboratory conditions using serum (DPP-lab) and to ELISA using serum. The agreements between the tests were determined using McNemar's chi2 test, Cohen's kappa coefficient (k) at the 95% confidence interval and prevalence-adjusted bias-adjusted kappa (PABAK). Of the 1130 dogs examined, 74.2% were non-reactive in all three tests applied. Based on the PCLV positive infection criterion, seroprevalence was 8.9% (101/1130) with 83.2% (84/101) of infected animals showing reactivity in all three tests while 7.8% (8/101) were reactive in DPP-field and ELISA and 8.9% (9/101) in DPP-lab and ELISA. The proportions of disagreements were substantial in all comparisons. Inter-rater reliability between DPP-field and ELISA (k=0.55; PABAK=0.78) and DPP-lab and ELISA (k=0.59; PABAK=0.81) were considered moderate, while that between DPP-field and DPP-lab (k=0.61; PABAK=0.79) was classified as marginally good. The proportion of seroconversions in DPP reactive animals that were initially ELISA indeterminate was significantly higher than in those that were DPP reactive but initially ELISA non-reactive. Restriction fragment length polymorphism analysis revealed the presence of Leishmania infantum, the etiologic agent of VL, in bone marrow samples from VL-infected animals. Our data showed that the techniques and protocols currently employed in the PCLV screening approach are not entirely reliable. Further consideration should be given to monitoring dogs with undetermined results in ELISA and a better training should be provided for health workers responsible for performing DPP tests applied under field conditions. PMID- 28992914 TI - A quantitative risk-analysis for introduction of Bovine Viral Diarrhoea Virus in the Netherlands through cattle imports. AB - Many countries have implemented control programmes aiming to eradicate Bovine Viral Diarrhoea Virus (BVDV). After obtaining the free status, a risk of re introduction of the virus through import may remain. Therefore the risk of introduction of BVDV through cattle imports in the Netherlands was quantified and the effectiveness of subsequent intervention measures was assessed. Data, literature and expert opinion were used to estimate values for input parameters to feed a stochastic simulation model. The probability that BVDV was imported was differentiated into persistently infected (PI) cattle, trojan cows that transmitted the virus vertically resulting in a PI foetus (TR) and transient infected cattle (TI). The import risk was stratified to beef, dairy, small scale, suckler, trade, veal and young stock herds. The intervention scenarios that were evaluated consisted of virus testing, a combination of virus testing and antibody testing in pregnant cows, abolishment of imports from high risk countries (i.e. countries with a BVDV prevalence >15%) and a combination of import restrictions and testing prior to import. Each year, 334 (5th and 95th percentile: 65-902) Dutch cattle herds were estimated to be infected with BVDV through import. Veal herds account for most infections associated with import (87%), whereas in the other herd types, only 9 beef, 6 dairy, 2 small scale, 16 suckler, 10 trade and 2 young stock herds are infected through imports per year. Import of PI cattle is the most important risk for introduction in veal herds, while import of TR cows is the main source of BVDV introduction in dairy, small scale and suckler herds. With the intervention scenarios, the number of BVDV infected herds in the Netherlands could be reduced to 81 and 58 herds per year when respectively virus testing or a combination of virus and antibody testing was applied or to 108 herds when import from high risk countries was abolished. With the scenario in which both import from high risk countries was abolished combined with virus and antibody testing, the number of BVDV infected herds could be reduced to 17 herds per year. The risk assessment showed that BVDV is regularly imported in the Netherlands. The import risk can effectively be reduced by implementing diagnostic testing prior to import and only import cattle with a favourable result, eventually combined with certain trade restrictions. PMID- 28992915 TI - A cross-sectional study for predicting tail biting risk in pig farms using classification and regression tree analysis. AB - Tail biting in pigs has been an identified behavioural, welfare and economic problem for decades, and requires appropriate but sometimes difficult on-farm interventions. The aim of the paper is to introduce the Classification and Regression Tree (CRT) methodologies to develop a tool for prevention of acute tail biting lesions in pigs on-farm. A sample of 60 commercial farms rearing heavy pigs were involved; an on-farm visit and an interview with the farmer collected data on general management, herd health, disease prevention, climate control, feeding and production traits. Results suggest a value for the CRT analysis in managing the risk factors behind tail biting on a farm-specific level, showing 86.7% sensitivity for the Classification Tree and a correlation of 0.7 between observed and predicted prevalence of tail biting obtained with the Regression Tree. CRT analysis showed five main variables (stocking density, ammonia levels, number of pigs per stockman, type of floor and timeliness in feed supply) as critical predictors of acute tail biting lesions, which demonstrate different importance in different farms subgroups. The model might have reliable and practical applications for the support and implementation of tail biting prevention interventions, especially in case of subgroups of pigs with higher risk, helping farmers and veterinarians to assess the risk in their own farm and to manage their predisposing variables in order to reduce acute tail biting lesions. PMID- 28992916 TI - Association of clinical signs after acute Schmallenberg virus infection with milk production and fertility in Swiss dairy cows. AB - Since its first occurrence in August 2011 in Germany and the Netherlands, the Schmallenberg virus (SBV) spread rapidly across Europe, where it caused production losses and abortions in ruminants as well as congenital malformations in the offspring of affected animals. Several studies have investigated the impact of SBV on fertility and production parameters in dairy cows at herd level. However, the impact of clinical disease at the animal level remained undetermined. This study aimed at estimating the impact of clinical disease during and after an infection with SBV on production and fertility parameters in individual Swiss dairy cows. Sixty-seven case and twenty-four control herds were selected according to whether cows had been showing clinical signs indicative of SBV during the epidemic from July to December 2012 in Switzerland. Of these 91 farms, production and fertility data from 388 cows with clinical signs from case herds were collected over a time period of four years, and compared to data from 932 cows without clinical signs originating from case or control herds. Milk yield, somatic cell count, number of inseminations and non-return at day 56 were analysed by means of hierarchical multivariable regression analysis. A significant drop in milk yield was observed in all groups during the SBV epidemic compared to the time before the infection, which amounted to 1.9kg per test day for clinical animals, 1.1kg for non-clinical animals from case herds and 0.6kg for non-clinical animals from control herds. A prolonged effect on milk yield was observed in clinical cows for about one year, suggesting that animals with clinical disease might not return to their previous milk production level in the current lactation after an acute infection with SBV. Clinical animals showed a significantly higher somatic cell count during the epidemic compared to the time before the infection. The number of inseminations per cow and production cycle was higher for clinical animals during the epidemic compared to the time periods before and after, but not significantly higher than for non-clinical animals from case and control herds. No difference regarding non-return at day 56 was found. Although the overall impact of the SBV epidemic in Switzerland was limited, the consequences could be substantial in farms with a high prevalence of clinical disease. PMID- 28992917 TI - The use of large databases to inform the development of an intestinal scoring system for the poultry industry. AB - There is increasing interest among the poultry industry to develop a comprehensive index that can be used to evaluate overall intestinal health and impact on production performance. The Intestinal Integrity (I2) index is a quantitative measurement tool used to assess the intestinal health of flocks that use the Health Tracking System (HTSi), a global surveillance system developed by Elanco Animal Health that captures flock-level information on health and performance. To generate an I2 index score for a flock, the presence of 23 intestinal health conditions is assessed and recorded, then entered into a mathematical equation. The objective of this study was to use data from the HTSi dataset to investigate the association between health conditions contained within the I2 index and five performance outcomes: average daily gain (ADG), mortality during the first week, feed conversion ratio (FCR), European Production Efficiency Factor (EPEF), and percent livability. At the time of analysis, the HTSi dataset contained information from the years 2006-2015 on 921,646 individual bird necropsy records from over 153,576 flocks at 1,570 broiler production flows across 53 countries. Flock-level production data used for this study were available for a subset of this population, 33,212 total flocks representing 6 US and 4 UK production flows. A separate multivariable linear or logistic regression model, with farm as a random effect, was built for each of the five outcomes mentioned above. All models controlled for clustering of flocks within production flows. Significant associations were found between key performance indicators and ten intestinal conditions (gross E. acervulina, gross E. maxima, microscopic E. maxima, gizzard erosions, roundworms, excessive intestinal fluid, thin intestines, excessive intestinal mucus, feed passage, and necrotic enteritis) and two management parameters (production flow and down time). Results from this study demonstrate that large databases, such as the HTSi database, can be used to inform and evaluate changes that can optimize intestinal health, and hence welfare, productivity, and sustainability of the poultry industry. In addition, large databases can be used for monitoring and benchmarking intestinal health of poultry and informing the development of innovative indices such as the I2 index for scoring intestinal health and providing routine data for its calculation. PMID- 28992918 TI - Assessing the impact of different persuasive messages on the intentions and behaviour of cat owners: A randomised control trial. AB - Owners of free-ranging domestic cats (Felis catus) are under increasing pressure to keep their pet contained within their house or yard, in an effort to reduce adverse impacts on cat welfare, ecosystem biodiversity and neighbourhoods. We conducted a randomised online experiment to assess the effectiveness of two persuasive messages to encourage cat owners to contain their pets. A total of 512 Australian cat owners, who currently do not contain their cats, were randomly assigned to view one of three short video messages: one framed to highlight the negative impact of cats' on wildlife and biodiversity ('wildlife protection' frame), one framed to highlight the health and safety benefits of keeping cats contained ('cat benefit' frame), and a control message focused on general information about cats ('neutral' frame). We assessed the impact of these video messages on two post-treatment outcome variables: (1) the intention of owners to contain their cat; and (2) the adoption of containment practices, based on a 4 week follow-up survey. Mediation analysis revealed both the 'wildlife protection' and 'cat benefit' messages increased owners' motivation to contain their cat and their beliefs that they could effectively contain their cat to achieve the desired outcomes (response efficacy). In turn, higher levels of motivation and response efficacy predicted increased cat containment intentions and increased adoption of cat containment. In addition, the response efficacy effects of the 'cat benefit' message were strengthened by the cat owner's bond to their pet, suggesting audience segmentation may improve the effectiveness of interventions. Implications for future intervention development are discussed. PMID- 28992919 TI - Genotypic and epidemiologic characterization of extended-spectrum cephalosporin resistant Salmonella enterica from US beef feedlots. AB - In the US, nontyphoidal Salmonellae are a common foodborne zoonotic pathogen causing gastroenteritis. Invasive Salmonella infections caused by extended spectrum cephalosporin resistant (ESCR) phenotypes are more likely to result in treatment failure and adverse health outcomes, especially in severe pediatric Salmonella infections where the extended-spectrum beta-lactams are the therapy of choice. To examine the genetic and epidemiologic characteristics of ESCR Salmonellae which may enter the food chain, we characterized 44 ceftiofur resistant Salmonella isolates from the National Animal Health Monitoring System (NAHMS) 2011 beef cattle feedlot health and management study. As part of the NAHMS Feedlot 2011 study, 5050 individual fecal samples from 68 large (1000+ head capacity) feedlots were cultured for Salmonella spp. The resulting 460 positive samples yielded 571 Salmonella isolates with 44 (8%) expressing an AmpC beta lactamase phenotype. These phenotypic blaCMY-2Salmonella isolates represented 8 serotypes, most commonly S. Newport (n=14, 32%), S. Typhimurium (n=13, 30%), and S. Reading (n=5, 11%), followed by S. Dublin, S. Infantis, S. Montevideo, S. Rough O:i;v:1;7, and S. Uganda. Carriage of the blaCMY-2 gene was confirmed for all isolates expressing an AmpC beta-lactamase phenotype by PCR. Additionally, all 44 isolates were shown to carry the blaCMY-2 gene on a large IncA/C plasmid, a gene/plasmid combination which has been previously reported in multiple species. Other plasmids, including IncN, FIC, and FIIA, were also detected in some isolates. Cattle fed chlortetracycline were less likely to be positive for a blaCMY-2Salmonella isolate in their enteric flora compared to those not receiving chlortetracycline during the feeding period. Carriage of blaCMY-2 was more prevalent in Salmonella isolates originating from lighter weight cattle, cattle fed tylosin and dairy breeds. Our characterization of the NAHMS Feedlot 2011 study Salmonella isolates with ESCR phenotype shows that while other cephalosporin resistance mechanisms have been reported in US cattle, specific serotypes harboring blaCMY-2 on IncA/C plasmids may be the dominant resistance genotype. PMID- 28992920 TI - Animal tuberculosis maintenance at low abundance of suitable wildlife reservoir hosts: A case study in northern Spain. AB - Animal tuberculosis (TB), which is caused by infection with members of the Mycobacterium tuberculosis complex (MTC), is a typical multi-host infection that flourishes at the livestock-wildlife interface. TB epidemiology is well characterized in the Mediterranean woodland habitats and Atlantic regions of southwestern Europe. However, much less is known about huge regions that do not form part of the two abovementioned settings, which have a low abundance of wild reservoirs. We hypothesized that MTC would be maintained in multi- rather than single-host communities in which wildlife would make a relatively low contribution to the maintenance of TB. Between 2011 and 2015, 7729 Eurasian wild boar (Sus scrofa) and 1729 wild ruminants were sampled for culture during hunting events on unfenced sites. In addition, 1058 wild ungulates were sampled on 23 fenced hunting estates. Infection prevalence data were modeled along with official data on cattle and goat TB, on livestock distribution and management, and on wild boar abundance. The mean individual MTC infection prevalence was 4.28% in wild boar, while the cattle skin test reactor percent was 0.17%. The prevalence of MTC infection in wild ungulates (mostly wild boar) from the fenced hunting estates was 11.6%. Modeling revealed that the main driver of TB in cattle was their management (beef; communal pastures). However, wild boar abundance, the prevalence of MTC infection in wild boar and the presence of fenced hunting estates also contributed to explaining cattle TB. The model used for goat TB identified communal pastures as a risk factor. The model for the prevalence of MTC infection in wild boar included wild boar abundance and communal pastures. We conclude that the MTC maintenance host community is most likely of a multi-host nature. While cattle and communal pastures pose the main risk regarding TB, it is also necessary to consider increasing wild boar densities and specific risks owing to fenced wildlife. We infer several management implications regarding wildlife management, the wildlife sampling strategy and laboratory testing, the peculiarities of fenced hunting estates, and the wildlife-livestock interface. PMID- 28992921 TI - Seroprevalence of brucellosis in cattle and selected wildlife species at selected livestock/wildlife interface areas of the Gonarezhou National Park, Zimbabwe. AB - A study was conducted to investigate seroprevalence and risk factors for Brucella species infection in cattle and some wildlife species in communities living at the periphery of the Great Limpopo Transfrontier Conservation Area in south eastern Zimbabwe. Three study sites were selected based on the type of livestock wildlife interface: porous livestock-wildlife interface (unrestricted); non porous livestock-wildlife interface (restricted by fencing); and livestock wildlife non-interface (totally absent or control). Sera were collected from cattle aged>=2years representing both female and intact male animals. Sera were also collected from selected wild ungulates from Mabalauta (porous interface) and Chipinda (non-interface) areas of the Gonarezhou National Park. Samples were screened for Brucellaantibodies using the Rose Bengal plate test and confirmed by the complement fixation test. Data were analysed by descriptive statistics and multivariate logistic regression modelling. In cattle, brucellosis seroprevalence from all areas was 16.7% (169/1011; 95% CI: 14.5-19.2%). The porous interface recorded a significantly (p=0.03) higher seroprevalence (19.5%; 95% CI: 16.1 23.4%) compared to the non-interface area (13.0%; 95% CI: 9.2-19.9%).The odds of Brucellaseropositivity increased progressively with parity of animals and were also three times higher (OR=3.0, 2.01, 5 and 10%) were located in the same direction as lower enrichment use ratio, liquid feed, trough feeding, floor feeding, restricted feed and in&outdoor pens. Results suggested that higher prevalences were not specifically connected to a particular system, but that all welfare outcomes were connected to several inappropriate features in the environment. This study highlights individual risk factors which can be considered to improve animal welfare, but also indicates the need to consider the environment as a whole because of potential factor combinations and confounds. Understanding of these requires a large scale database, which can be drawn from assessments carried out as part of farm assurance and support evidence based advice and future formulation of standards for good practice. PMID- 28992927 TI - First study on domestic dog ecology, demographic structure and dynamics in Bamako, Mali. AB - BACKGROUND: For the planning of an effective dog mass vaccination campaign against rabies in Africa, it is crucial to know more about the dog population. In this paper we describe for the first time the dog ecology, demographic structure and population dynamics of a domestic dog population in Bamako, Mali. In 2010 and 2011, we visited 2956 randomly selected compounds. Questionnaire data was collected on the compound and household level and on each dog individually. Dog owning households were followed every six months during one (dog-owning households identified in 2011) or two years (dog-owning households identified in 2010) for the successive collection of dog demography data. RESULTS: We recorded 379 dogs in 279 compounds. The dog human ratio was estimated at 1:121, and the extrapolation of the domestic dog population in Bamako results in an estimate of 14 906 dogs (95% CI 13 041-17 037). The female male ratio was 1:2.8. A high proportion of young dogs was found as a result of a high turnover rate in the population. Mortality within the first year of life was high, and dogs had a life expectancy at birth of 2.5 years. Using a Leslie matrix, we estimated the annual dog population growth to be 20%. Christians were more likely to be dog owners than Muslims. Another factor favouring dog ownership was belonging to the ethnic group of Bobo or Malinke. Dogs were mainly used as watchdogs and fed with household leftovers and garbage. They were most often obtained and given away without remuneration. CONCLUSIONS: This work contributes vital information towards planning effective and sustainable dog rabies control programmes for the district of Bamako. Due to the high turnover rate, we recommend repeated mass vaccination campaigns of at least 70% of the owned dogs at yearly intervals. In addition, dog-owners need to be educated on good dog management. PMID- 28992928 TI - Domestic dog roaming patterns in remote northern Australian indigenous communities and implications for disease modelling. AB - Although Australia is canine rabies free, the Northern Peninsula Area (NPA), Queensland and other northern Australian communities are at risk of an incursion due to proximity to rabies infected islands of Indonesia and existing disease spread pathways. Northern Australia also has large populations of free-roaming domestic dogs, presenting a risk of rabies establishment and maintenance should an incursion occur. Agent-based rabies spread models are being used to predict potential outbreak size and identify effective control strategies to aid incursion preparedness. A key component of these models is knowledge of dog roaming patterns to inform contact rates. However, a comprehensive understanding of how dogs utilise their environment and the heterogeneity of their movements to estimate contact rates is lacking. Using a novel simulation approach - and GPS data collected from 21 free-roaming domestic dogs in the NPA in 2014 and 2016 - we characterised the roaming patterns within this dog population. Multiple subsets from each individual dog's GPS dataset were selected representing different monitoring durations and a utilisation distribution (UD) and derived core (50%) and extended (95%) home ranges (HR) were estimated for each duration. Three roaming patterns were identified, based on changes in mean HR over increased monitoring durations, supported by assessment of maps of daily UDs of each dog. Stay-at-home dogs consolidated their HR around their owner's residence, resulting in a decrease in mean HR (both core and extended) as monitoring duration increased (median peak core and extended HR 0.336 and 3.696ha, respectively). Roamer dogs consolidated their core HR but their extended HR increased with longer monitoring durations, suggesting that their roaming patterns based on place of residence were more variable (median peak core and extended HR 0.391 and 6.049ha, respectively). Explorer dogs demonstrated large variability in their roaming patterns, with both core and extended HR increasing as monitoring duration increased (median peak core and extended HR 0.650 and 9.520ha, respectively). These findings are likely driven by multiple factors that have not been further investigated within this study. Different roaming patterns suggest heterogeneous contact rates between dogs in this population. These findings will be incorporated into disease-spread modelling to more realistically represent roaming patterns and improve model predictions. PMID- 28992929 TI - Antibiotic use by farmers to control mastitis as influenced by health advice and dairy farming systems. AB - Mastitis is a bacterial disease common in dairy farms. Although knowledge about mastitis and its optimal technical management and treatment is now available, some dairy farmers still use antibiotics in inappropriate ways. Antibiotic use by farmers can be influenced by personal restraints and motivations, but it can be assumed that external drivers are also influential. The main purpose of this article is thus to analyse the choices of antibiotic and alternative medicine use for mastitis treatment and investigate the possible influence of two unexplored external drivers in dairy farms: (i) the health advice offered to farmers by farm advisors and veterinarians, (ii) the dairy farming system, as defined by combining the market valuation chosen for the milk, the level of intensification, and the perceived pressure related to investments. Research was based on 51 individual semi-structured interviews with farmers and their corresponding veterinarians and farm advisors. Based on verbatim, the use of antibiotics and alternative medicine by farmers for mastitis treatment, the vet-farmers interactions, and the dairy farming systems are described. The advisory relationships between farmers and farm advisors and between farmers and veterinarians influenced the implementation of selective dry cow therapy, but had very little effect on the use of alternative medicines by farmers, who were more willing to experiment alternative medicines than their advisors. The dairy farming system had very little influence on antibiotic use: some misuse of antibiotics was found whatever the farming system. Systematic dry cow therapy was also a widespread habit in all dairy farming systems except organic. The use of alternative medicine was common in all farming systems. PMID- 28992930 TI - Risk for zoonotic Salmonella transmission from pet reptiles: A survey on knowledge, attitudes and practices of reptile-owners related to reptile husbandry. AB - Reptiles are becoming increasingly popular as pets. Those animals are reservoirs of a wide variety of Salmonella serotypes, that may be transmitted to warm blooded animals, including humans. Accordingly, good hygiene practices related to husbandry are important for prevention of Reptile-associated salmonellosis (RAS). A cross-sectional study was conducted among reptile owners, by administration of a detailed questionnaire. In addition, the cloacal swabs of the sampled reptiles were screened for Salmonella spp. and the husbandry management practices were evaluated in order to assess any possible link between the presence of Salmonella spp. and the hygiene practices. The response rate to the questionnaire was 66.6% (100 out of 150 contacted owners). In 26 out of 100 families, members at risk of RAS (children and elderly) were present. One hundred animals were screened for the presence of Salmonella spp. The prevalence of Salmonella spp. carriers was 57% (Confidence interval 47-66%). Co-habitation of the animals with other reptiles in the same terrarium was associated with a 2-fold increase in the risk of infection by Salmonella spp.(Odds ratio=2.3, CI 1.2;13, p=0.02). Animals handled by owners that did not report washing their hands after the cleaning procedures or the handling were exposed to a 3-fold increase in the risk of infection (OR=3.1, CI 1.1;16, p=0.019). When drinking water was not replaced regularly, the animals were 7 times more exposed to infection (OR=6.8, CI 1.8;25, p=0.005). When the diet was constituted by rodents, 27 out of 48 reptiles (56.3%) were fed with live animals. In the present survey the typical reptile owner was a person, aware of ethological aspects of reptile husbandry but ignorant of some ethical recommendations and poorly informed about the health risks for himself and for the other family members. Prevention of RAS must rely mainly on information and education, with the veterinarian health bodies primarily involved in this difficult task. PMID- 28992931 TI - Livestock mortality and offtake in sheep and goat flocks of livestock owners making use of services offered by paravets in West Afghanistan. AB - In the present study, we quantified the effect of livestock services provided through paravets (intermediate-level training in veterinary medicine) on mortality and offtake of small ruminants in Western Afghanistan for the years 2010, 2011 and 2013. We compared mortality in adult and in young stock, and offtake of young stock of 120 livestock owners that made use of the paravet services (Users) with 120 livestock owners who did not make use of these services (Non-users). Security issues in the districts under study influenced the choice of villages. Within villages, livestock owners were purposively selected based on their known use of the services, including the provision of biologicals such as anthelmintics and vaccines. In addition, we subdivided both categories into 'partial' and 'full' based on the intensity of use of biologicals. Paravets were not only trained on preventive and curative veterinary medicine, they were also trained in extension and trained on adhering to a cold-chain and applying quality biologicals. For Non-users there was the possibility to buy biologicals through a local market or bazaar. In Afghanistan, local markets have an extensive supply of vaccines, anthelmintics, and medicines from a variety of sources, often not handled appropriately and therefore of varying quality. The results indicated that livestock owners making partial or full use of the paravet services had statistically significant better animal health and production results. The mortalities in adult stock, expressed as Incidence Rate Ratios (IRRs), for the partial-Users and full-Users categories were estimated to be respectively 0.80 and 0.73 times the mortality observed in the partial Non-users', the reference category. A similar result was observed for young stock mortality with estimated IRRs of 0.81 and 0.77 for partial and full-Users category respectively. The offtake for partial- and full-Users category livestock owners were 1.24 and 1.21 times higher compared with the reference category. In conclusion, we demonstrated significant improvement of health and production parameters in small ruminants' flocks of owners making use of the services of the DCA-trained paravets, emphasizing the importance of this sustainable and effective system of private veterinary service delivery in Afghanistan. PMID- 28992932 TI - A financial cost-benefit analysis of eradicating virulent footrot. AB - In 2008, virulent footrot was detected in sheep in south-west Norway. Footrot is caused by Dichelobacter nodosus, and the outbreak was linked to live sheep imported from Denmark in 2005. A large-scale program for eradicating the disease was implemented as a joint industry and governmental driven eradication project in the years 2008-2014, and continued with surveillance and control measures by the Norwegian Food Safety Authority from 2015. The cost of the eradication program including surveillance and control measures until 2032 was assumed to reach approximately ?10.8 million (NOK 90 million). A financial cost-benefit analysis, comparing costs in the eradication program with costs in two simulated scenarios, was carried out. In the scenarios, designated ModerateSpread (baseline) and SlowSpread, it was assumed that the sheep farmers would undertake some voluntary measures on their own that would slow the spread of the disease. The program obtained a positive NPV after approximately 12 years. In a stochastic analysis, the probabilities of a positive NPV were estimated to 1.000 and to 0.648 after 15 years and to 0.378 and 0.016 after ten years, for the ModerateSpread and SlowSpread scenarios respectively. A rapid start-up of the program soon after the detection of the disease was considered crucial for the economic success as the disease would have become more widespread and probably raised the costs considerably at a later start-up. PMID- 28992933 TI - Early life indicators predict mortality, illness, reduced welfare and carcass characteristics in finisher pigs. AB - The objective of this study was to investigate associations between early life indicators, lactation management factors and subsequent mortality, health, welfare and carcass traits of offspring. A total of 1016 pigs from a batch born during one week were used. During lactation, number of liveborn piglets, stillborn and mummies, sow parity, number of times cross-fostered, weaning age, birth and weaning body weight (BW) were collected. Mortality was recorded throughout the offspring production cycle. Prior to slaughter, pigs were scored for lameness (1=non-lame to 3=severely lame). At slaughter, tail lesions were scored (0=no lesion to 4=severe lesion) and cold carcass weight (CCW), lean meat%, presence of pericarditis and heart condemnations were recorded. Additionally, lungs were scored for pleurisy (0=no lesions to 4=severely extended lesions) and enzootic pneumonia (EP) like lesions. There was an increased risk of lameness prior to slaughter for pigs born to first parity sows (P<0.05) compared with pigs born to older sows. Sow parity was a source of variation for cold carcass weight (P<0.05) and lean meat% (P<0.05). Pigs born in litters with more liveborn pigs were at greater risk of death and to be lame prior to slaughter (P<0.05). Pigs that were cross-fostered once were 11.69 times, and those that were cross-fostered >=2 times were 7.28, times more likely to die compared with pigs that were not cross-fostered (P<0.05). Further, pigs that were cross fostered once were at greater risk of pericarditis and heart condemnations compared with pigs that were not cross-fostered (P<0.05). Pigs with a birth BW of <0.95kg were at higher mortality risk throughout the production cycle. There was an increased risk of lameness, pleurisy, pericarditis and heart condemnations (P<0.05) for pigs with lower weaning weights. Additionally, heavier pigs at weaning also had higher carcass weights (P<0.05). There was an increased risk of lameness for pigs weaned at a younger age (P<0.05). Males were 2.27 times less likely to receive a score of zero for tail biting compared with female pigs. Results from this study highlight the complex relationship between management, performance and disease in pigs. They confirm that special attention should be given to lighter weight pigs and pigs born to first parity sows and that cross fostering should be minimised. PMID- 28992934 TI - Subtrochanteric fractures: Issues and challenges. PMID- 28992935 TI - Initial Experience in the Treatment of "Borderline Resectable" Pancreatic Adenocarcinoma. AB - INTRODUCTION: A borderline resectable group (APBR) has recently been defined in adenocarcinoma of the pancreas. The objective of the study is to evaluate the results in the surgical treatment after neoadjuvancy of the APBR. METHOD: Between 2010 and 2014, we included patients with APBR in a neoadjuvant and surgery protocol, staged by multidetector computed tomography (MDCT). Treatment with chemotherapy was based on gemcitabine and oxaliplatin. Subsequently, MDCT was performed to rule out progression, and 5-FU infusion and concomitant radiotherapy were given. MDCT and resection were performed in absence of progression. A descriptive statistical study was performed, dividing the series into: surgery group (GR group) and progression group (PROG group). RESULTS: We indicated neoadjuvant treatment to 22 patients, 11 of them were operated, 9 pancreatoduodenectomies, and 2 distal pancreatectomies. Of the 11 patients, 7 required some type of vascular resection; 5 venous resections, one arterial and one both. No postoperative mortality was recorded, 7 (63%) had any complications, and 4 were reoperated. The median postoperative stay was 17 (7-75) days. The pathological study showed complete response (ypT0) in 27%, and free microscopic margins (R0) in 63%. At study clossure, all patients had died, with a median actuarial survival of 13 months (9,6-16,3). The median actuarial survival of the GR group was higher than the PROG group (25 vs. 9 months; p < 0.0001). CONCLUSION: The neoadjuvant treatment of APBR allows us to select a group of patients in whom resection achieves a longer survival to the group in which progression is observed. Post-adjuvant pancreatic resection requires vascular resection in most cases. PMID- 28992936 TI - [Short-term exercise-based cardiac rehabilitation induced changes in cardiorespiratory, mechanical and neuromuscular responses to progressive exercise testing]. AB - : Previous studies showed that changes in peak of oxygen uptake value (VO2peak) with training were poorly related to changes in Maximal Tolerated Power output (MTP) among patients with cardiovascular disease. This result could be due to a difference between cardiopulmonary adaptation to training and the skeletal muscle conditioning. OBJECTIVE: The aim of the study was to compare the responses to exercise training of electromyographic activities of vastus lateralis (rms-EMG) and respiratory parameters. METHODS: Nine cardiac patients (64.0+/-3.1y, 172.9+/ 4.8cm, 83.4+/-16.3kg, BMI: 27.8+/-4.5) performed an incremental cycling exercise test to determine MTP, VO2peak and peak values of heart rate, before and after an aerobic training. Ventilatory thresholds were respectively determined as the breakpoint in the curve of carbon dioxide output against oxygen uptake plot (VT1) and the point at which the ratio of minute ventilation to carbon dioxide output starts to increase (VT2). EMGth1 and EMGth2 were defined as the first and the second breakpoints in the rms-EMG - power output relationship. RESULTS: Short term exercise training (23.7+/-8.8 days) induced a significant increase in VO2peak (P=0.004), MTP (P=0.015), VT1 (P=0.001) and VT2 (P=0.001). Changes in VO2peak only attained the survival criteria (3.5+/-2.9mLmin-1kg-1). No significant differences (P>0.05) existed between mean power values of VT1 and EMGth1 (60.5+/-4.1 vs. 59.2+/-9.6% of MTP, respectively), or between VT2 and EMGth2 (78.3+/-5.7 vs. 80.2+/-5.2% of MTP). After training, EMGth1 occurred significantly before VT1 (60.5+/-6.2 vs. 64.8+/-4.8% of MTP, P=0.049). CONCLUSION: This might be taken into account for prescribing exercise rehabilitation according initial clinical limitations of patients. PMID- 28992938 TI - Bilateral carpal tunnel syndrome - A review. AB - Carpal tunnel syndrome (CTS) is the most common upper extremity compressive neuropathy, with a prevalence of 3%-5% in the general population, and 6% in the group of females over the age of 40. It occurs about five times more common in females, with 2 peaks observed, in the 6th and 8th decades of life. Bilateral manifestation is more common than unilateral (60%), but significantly more often begins or is more strongly expressed in the dominant hand. Possible anatomical abnormalities underlying the development of CTS account for about 5% of cases. More and more scientific data confirm the significant role of central nervous system processes (including central sensitization) in the development of carpal tunnel syndrome, and changes in central nervous system body somatotopic representation, resulting from prolonged median nerve pathology, are described in consistence with the brain plasticity concept. This central involvement of bilateral CTS may explain that a proportion of patients following surgery for one hand experience improvement also in the non-operated hand. PMID- 28992937 TI - Substrate Specificity of the Kinase P-TEFb towards the RNA Polymerase II C Terminal Domain. AB - The positive transcription elongation factor b (P-TEFb) promotes transcription elongation through phosphorylation of the RNA polymerase II C-terminal domain. This process is not well understood, partly due to difficulties in determining the specificity of P-TEFb toward the various heptad repeat motifs within the C terminal domain. A simple assay using mass spectrometry was developed to identify the substrate specificity of the Drosophila melanogaster P-TEFb (DmP-TEFb) in vitro. This assay demonstrated that DmP-TEFb preferentially phosphorylates Ser5 and, surprisingly, that pre-phosphorylation or conserved amino acid variation at the 7-position in the heptad can alter DmP-TEFb specificity, leading to the creation of distinct double-phosphorylation marks. PMID- 28992940 TI - Clinical and scientific debates on atherosclerosis: The truth lies somewhere in the middle. PMID- 28992941 TI - Corrigendum to "Chemical, biological, and DNA markers for tracing slaughterhouse effluent" [Environ. Res. 156 (2017) 534-541]. PMID- 28992939 TI - Kidney function, bone-mineral metabolism markers, and future risk of peripheral artery disease. AB - BACKGROUND AND AIMS: Reduced kidney function is a risk factor for lower-extremity peripheral artery disease (PAD). However, the associations of novel filtration markers with PAD are yet to be quantified. Moreover, little is known on whether bone-mineral metabolism (BMM) markers are related to incident PAD beyond kidney function. METHODS: Using data from 12,472 participants at baseline (1990-1992) of the Atherosclerosis Risk in Communities (ARIC) study, we comprehensively quantified the associations of kidney related markers with incident PAD (defined as hospitalizations with diagnosis of lower-extremity atherosclerosis, revascularization, or amputation). Kidney related markers of interest included estimated glomerular filtration rate (eGFR) (based on creatinine, cystatin C, and both), cystatin C, beta-2 microglobulin (B2M), and BMM markers (serum fibroblast growth factor 23, parathyroid hormone, calcium, and phosphorus). RESULTS: During a median follow-up of 21 years, 471 participants developed incident PAD. Low eGFR was significantly associated with future PAD risk, with slightly stronger relationship when cystatin C was used (adjusted hazard ratio [HR] 6.3-8.3 for eGFR <30 and 2.4-3.5 for eGFR 30-59 vs. eGFR >=90 mL/min/1.73 m2). Among all filtration markers, B2M had the strongest association with incident PAD (HR for top vs. bottom quartile 2.60 [95% CI: 1.91-3.54] for B2M vs. 1.20 [0.91-1.58] for creatinine-based eGFR). Among BMM markers, only phosphorus remained significant for PAD risk beyond potential confounders, including kidney function (HR 1.47 [1.11-1.94] in top quartile). CONCLUSIONS: Kidney dysfunction was independently associated with future PAD risk, particularly when assessed with cystatin C and B2M. Among the BMM markers tested, phosphorus was most robustly associated with incident PAD beyond kidney function. Our results suggest the potential usefulness of novel filtration markers for PAD risk assessment and the possible role of phosphorus in the pathophysiology of PAD. PMID- 28992942 TI - Erratum to "A watershed model of individual differences in fluid intelligence" [Neuropsychologia 91 (2016) 186-198]. PMID- 28992943 TI - Perturbed cooperative-state feedback strategy for model predictive networked control of interconnected systems. AB - A perturbed cooperative-state feedback (PSF) strategy is presented for the control of interconnected systems in this paper. The subsystems of an interconnected system can exchange data via the communication network that has multiple connection topologies. The PSF strategy can resolve both issues, the sensor data losses and the communication network breaks, thanks to the two components of the control including a cooperative-state feedback and a perturbation variable, e.g., ui=Kijxj+wi. The PSF is implemented in a decentralized model predictive control scheme with a stability constraint and a non-monotonic storage function (DeltaV(x(k))>=0), derived from the dissipative systems theory. Numerical simulation for the automatic generation control problem in power systems is studied to illustrate the effectiveness of the presented PSF strategy. PMID- 28992944 TI - Response by Sarfo and Ovbiagele to letter regarding "potential role of tele rehabilitation to address barriers to implementation of physical therapy among West African stroke survivors: A cross-sectional survey". PMID- 28992945 TI - Pathogenicity of the LHON variant m.3472T>C is uncertain. PMID- 28992946 TI - Author reply: "MtDNA m.3472T>C could be classified as a primary mutation of Leber's hereditary optic neuropathy". PMID- 28992947 TI - Optimizing oil spill cleanup efforts: A tactical approach and evaluation framework. AB - Although anthropogenic oil spills vary in size, duration and severity, their broad impacts on complex social, economic and ecological systems can be significant. Questions pertaining to the operational challenges associated with the tactical allocation of human resources, cleanup equipment and supplies to areas impacted by a large spill are particularly salient when developing mitigation strategies for extreme oiling events. The purpose of this paper is to illustrate the application of advanced oil spill modeling techniques in combination with a developed mathematical model to spatially optimize the allocation of response crews and equipment for cleaning up an offshore oil spill. The results suggest that the detailed simulations and optimization model are a good first step in allowing both communities and emergency responders to proactively plan for extreme oiling events and develop response strategies that minimize the impacts of spills. PMID- 28992949 TI - SH3 dependent cell death signaling of the avian chB6 alloantigen. AB - In chickens, B cells develop in the bursa of Fabricius, a unique organ for B cell development. Most B cells will die within the bursa, mirroring cell losses seen in mammalian bone marrow as central tolerance is enforced at the transition to mature cells. B cell responses are shaped by a complex interplay of signals. Signals in addition to BCR that impact central tolerance have recently been described. We have been interested in chB6, a novel alloantigen on B cells in the chicken. chB6 is found in close proximity to the BCR and can trigger apoptosis after cross-linking by antibody. chB6 has two Ig domains, placing it within the CD2/SLAM family of molecules, but its cytoplasmic domain is unique. We have used a site-specific mutagenesis approach to show that an SH3 binding site in chB6 is required for the induction of apoptosis, suggesting parallels to CD2 signaling. PMID- 28992950 TI - Future Horizons in Allergy. AB - There are several advances in diagnosis and management for the otolaryngologist treating allergy. These include new technologies and the refinement of current techniques, and reflect overall trends in health care toward personalized medicine. Local immunoglobulin, urinary leukotriene E4, lipidomics, microRNA within extracellular vesicles, and optical rhinometry all offer to improve the diagnostic accuracy of allergy and related nonallergic conditions. New delivery systems for intranasal steroids and antihistamines, recombinant allergens, advances in allergen immunotherapy delivery, and biologics will improve current management options. These developments will aid the otolaryngologist in diagnosing and treating allergy and related diseases. PMID- 28992951 TI - The Role of Allergy in Otologic Disease. AB - Allergy is commonly associated with conditions such as rhinitis, sinusitis, and asthma, but the relationship between allergy and otologic diseases is less clear. This article examines the evidence for a relationship between allergic disease and several common otologic conditions, including otitis media with effusion, eosinophilic otitis media, and Meniere's disease. PMID- 28992952 TI - Ruminants (Giraffidae and Bovidae) from Kanapoi. AB - We update here our recent revision of the Kanapoi ruminants and describe recently collected material. We now regard the occurrence of reduncins as doubtful, we revise the identification of a large raphicerin as being more probably Gazella, and we add Gazella cf. janenschi and the Cephalophini to the faunal list. New material of Tragelaphus kyaloi suggests that this species held its head unlike other tragelaphins, and was not an exclusive dedicated browser, but Kanapoi pre dates the Pliocene change of Sivatherium, Aepyceros, Alcelaphini, and even Tragelaphini toward more grazing diets. Kanapoi shares several ruminant taxa with sites in Ethiopia and Tanzania, attesting to latitudinal exchanges. PMID- 28992948 TI - The potential of real-time fMRI neurofeedback for stroke rehabilitation: A systematic review. AB - Real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback aids the modulation of neural functions by training self-regulation of brain activity through operant conditioning. This technique has been applied to treat several neurodevelopmental and neuropsychiatric disorders, but its effectiveness for stroke rehabilitation has not been examined yet. Here, we systematically review the effectiveness of rt-fMRI neurofeedback training in modulating motor and cognitive processes that are often impaired after stroke. Based on predefined search criteria, we selected and examined 33 rt-fMRI neurofeedback studies, including 651 healthy individuals and 15 stroke patients in total. The results of our systematic review suggest that rt-fMRI neurofeedback training can lead to a learned modulation of brain signals, with associated changes at both the neural and the behavioural level. However, more research is needed to establish how its use can be optimized in the context of stroke rehabilitation. PMID- 28992953 TI - [Anterior uveitis as the presenting sign of chronic lymphocytic leukemia]. PMID- 28992954 TI - [Eyelid hematomas secondary to acute promyelocytic leukemia]. PMID- 28992955 TI - [Hyperviscosity syndrome in Waldenstrom's macroglobulinemia]. PMID- 28992956 TI - Is manual ultrasonographic measurement of carotid intima-media thickness a reproducible cardiovascular biomarker? AB - To establish the ability of a potential biomarker to discriminate between diseased and healthy subjects, it is essential to know the intrinsic variability of the methods used to measure the biomarker. This aspect is especially important in the ultrasonographic measurement of carotid intima-media thickness, where submillimetric variations due largely to the unrecognized lack of precision in the ultrasonographic technique can have a significant clinical impact on the classification of cardiovascular risk. This article aims to present the evidence about the reproducibility of carotid intima-media thickness measured by ultrasonography to discuss whether the variability inherent in the technique can influence the potential of this parameter as a biomarker. PMID- 28992957 TI - Clozapine-Associated Aspiration Pneumonia: Case Series and Review of the Literature. PMID- 28992958 TI - Positive childhood experiences predict less psychopathology and stress in pregnant women with childhood adversity: A pilot study of the benevolent childhood experiences (BCEs) scale. AB - This pilot study examined the psychometric properties of the Benevolent Childhood Experiences (BCEs) scale, a new instrument designed to assess positive early life experiences in adults with histories of childhood maltreatment and other adversities. A counterpart to the Adverse Childhood Experiences (ACEs) questionnaire, the BCEs was developed to be multiculturally-sensitive and applicable regardless of socioeconomic position, urban-rural background, or immigration status. Higher levels of BCEs were hypothesized to predict lower levels of psychopathology and stress beyond the effects of ACES in a sample of ethnically diverse, low-income pregnant women. BCEs were also expected to show adequate internal validity across racial/ethnic groups and test-retest stability from the prenatal to the postnatal period. Participants were 101 pregnant women (M=29.10years, SD=6.56, range=18-44; 37% Latina, 22% African-American, 20% White, 21% biracial/multiracial/other; 37% foreign-born, 26% Spanish-speaking) who completed the BCEs and ACEs scales; assessments of prenatal depression and post traumatic stress disorder (PTSD) symptoms, perceived stress, and exposure to stressful life events (SLEs) during pregnancy; and demographic information. Higher levels of BCEs predicted less PTSD symptoms and SLEs, above and beyond ACEs. The BCEs showed excellent test-retest reliability, and mean levels were comparable across racial/ethnic and Spanish-English groups of women. Person oriented analyses also showed that higher levels of BCEs offset the effects of ACEs on prenatal stress and psychopathology. The BCEs scale indexes promising promotive factors associated with lower trauma-related symptomatology and stress exposure during pregnancy and illuminates how favorable childhood experiences may counteract long-term effects of childhood adversity. PMID- 28992959 TI - A national survey of characteristics of child advocacy centers in the United States: Do the flagship models match those in broader practice? AB - Child Advocacy Centers (CAC) emphasize developing effective cross-agency collaborations between workers involved in serious abuse investigations to foster improvements in agency outcomes, and to minimize distress, confusion and uncertainty for children and families. This study examined the characteristics of CACs, whether models in practice match the predominant model presented in the research literature. Directors of CACs in the United States that were members of the National Children's Alliance (NCA) mailing list (n=361) completed an online survey in 2016. While some core characteristics were ubiquitous across CACs, the data suggests that different types of CACs exist defined by characteristics that are not prescribed under NCA principles, but which are arguably relevant to the quality of the response. From the results of a cluster analysis, the researchers propose a typology of CACs that reflects the development and integration of centers: (a) core CAC services (i.e. interviewing & cross-agency case review); (b) an aggregator of external services, and (c) a more centralized full-service CAC. Further research is needed to understand how these variations may impact practice and outcomes; this is particularly important considering many CACs do not match the full-service models most commonly examined in the research literature, which limits the degree to which these findings apply to CACs generally. This article proposes further research framed by the need to better understand how different parts of the response impact on outcomes for children and families affected by abuse. PMID- 28992960 TI - Tp-e interval and Tp-e/QT ratio in patients with celiac disease. AB - OBJECTIVES: Celiac disease is a chronic immune-mediated disease of the small intestine. It has been known that dilated cardiomyopathy and ischemic coronary artery disease have become more frequent in patients with celiac disease. The aim of the study was to assess Tp-e interval and Tp-e/QT ratio in patients with celiac disease. MATERIAL AND METHODS: This study was conducted at a single center in collaboration with gastroenterology and cardiology clinics. Between January 2014 and June 2015, a total of 76 consecutive patients were enrolled (38 patients with celiac disease and 38 control subjects). Tp-e interval, Tp-e/QT and Tp-e/QTc ratio were measured from the 12-lead electrocardiogram. RESULTS: Tp-e interval (64.2+/-11.0 vs. 44.5+/-6.0; p<0.001), Tp-e/QT ratio (0.18+/-0.02 vs. 0.13+/ 0.02; p<0.001) and Tp-e/QTc ratio (0.16+/-0.02 vs. 0.11+/-0.01; p<0.001) were significantly higher in patients with celiac disease than control subjects. There was a significant positive correlation between Tp-e/QTc ratio and disease duration in patients with celiac disease (r=0.480, p=0.003) and also there was a significant positive correlation between Tp-e/QTc ratio and erythrocyte sedimentation rate (r=0.434, p<0.001). CONCLUSIONS: Our study showed that Tp-e interval, Tp-e/QT and Tp-e/QTc ratios were increased in patients with celiac disease. Whether these changes increase the risk of ventricular arrhythmia deserve further studies. PMID- 28992961 TI - The effectiveness of fish feeding behaviour in mirroring trawling-induced patterns. AB - The ability to observe and predict trawling-induced patterns at spatial and temporal scales that are relevant to inform realistic management strategies is a challenge which scientists have consistently faced in recent decades. Here, we use fish feeding behaviour, a biological trait easily impaired by trawling disturbance, to depict alterations in fish condition (i.e. individual fitness) and feeding opportunities. The benthivorous fish Mullus barbatus barbatus was selected as a model species. The observed trends of responses to trawling in prey species confirmed the effectiveness of a non-trawled zone in sustaining higher levels of diet diversity (e.g. quantity and quality of ingested prey) and fish condition values (e.g. morphometric and physiological Condition Index). Changes observed in fish prey selection confirmed the role of trawling disturbance in modifying the local soft bottoms community, producing alterations of prey availability that trigger shifts in fish diet. Trawling-induced feeding patterns, mirrored through stomach contents, can positively or negatively affect fish condition, the main driver of population dynamics in maintaining carrying capacity levels. Due to the widespread socio-economic value of the red mullet fishery, and the current exploitation status, evidence gathered by the proposed bottom-up trait based approach might inform future trawling adaptation strategies, and tailor spatial conservation measures supporting an Ecosystem Based Fisheries Management. PMID- 28992962 TI - The long- and short-term variability of breathing induced tumor motion in lung and liver over the course of a radiotherapy treatment. AB - PURPOSE: To evaluate the short and long-term variability of breathing induced tumor motion. MATERIALS AND METHODS: 3D tumor motion of 19 lung and 18 liver lesions captured over the course of an SBRT treatment were evaluated and compared to the motion on 4D-CT. An implanted fiducial could be used for unambiguous motion information. Fast orthogonal fluoroscopy (FF) sequences, included in the treatment workflow, were used to evaluate motion during treatment. Several motion parameters were compared between different FF sequences from the same fraction to evaluate the intrafraction variability. To assess interfraction variability, amplitude and hysteresis were compared between fractions and with the 3D tumor motion registered by 4D-CT. Population based margins, necessary on top of the ITV to capture all motion variability, were calculated based on the motion captured during treatment. RESULTS: Baseline drift in the cranio-caudal (CC) or anterior poster (AP) direction is significant (ie. >5 mm) for a large group of patients, in contrary to intrafraction amplitude and hysteresis variability. However, a correlation between intrafraction amplitude variability and mean motion amplitude was found (Pearson's correlation coefficient, r = 0.72, p < 10-4). Interfraction variability in amplitude is significant for 46% of all lesions. As such, 4D-CT accurately captures the motion during treatment for some fractions but not for all. Accounting for motion variability during treatment increases the PTV margins in all directions, most significantly in CC from 5 mm to 13.7 mm for lung and 8.0 mm for liver. CONCLUSION: Both short-term and day-to-day tumor motion variability can be significant, especially for lesions moving with amplitudes above 7 mm. Abandoning passive motion management strategies in favor of more active ones is advised. PMID- 28992963 TI - Transapical transcatheter aortic valve replacement with a novel transcatheter aortic valve replacement system in high-risk patients with severe aortic valve diseases. AB - OBJECTIVES: The clinical experience of a novel transapical transcatheter aortic valve replacement system, the J-Valve (JC Medical Inc, Burlingame, Calif), in high-risk patients with severe aortic valve diseases is limited. METHODS: A total of 107 high-risk patients (mean age, 74.4 +/- 5.2 years) underwent transcatheter aortic valve replacement with the J-Valve from March 2014 to July 2015, which included 63 patients with aortic stenoses and 44 patients with aortic regurgitation. Echocardiography and contrast-enhanced computed tomography were used to evaluate patients' baseline characteristics and their follow-up conditions. RESULTS: The J-Valve was successfully implanted in 102 patients (95.3%). Five patients (4.7%) underwent conversion to open surgery. The overall mortality was 4.7% (n = 5) at both 30 days and 6 months, whereas subgroup mortality was 6.3% (n = 4) in the aortic stenosis group and 2.3% (n = 1) in the aortic regurgitation group. Permanent pacemakers were implanted in 5 patients (4.7%). In the aortic stenosis group, paravalvular regurgitation was observed as none or trace in 54.2% of patients (n = 32), mild in 42.4% of patients (n = 25), and moderate in 3.4% of patients (n = 2) postprocedure. The mean aortic gradient decreased from 56.7 +/- 15.2 mm Hg to 14.4 +/- 7.8 mm Hg (P < .01). The peak aortic valve velocity declined from 4.76 +/- 0.6 m/s to 2.45 +/- 0.57 m/s (P < .01). In the patients with aortic regurgitation, paravalvular regurgitation was none or trace in 74.4% (n = 32), mild in 23.3% (n = 10), and 2.3% (n = 1) after the procedure. Mean aortic gradient was 7.1 +/- 2.9 mm Hg. CONCLUSIONS: Transcatheter aortic valve replacement by the J-Valve is an adequate clinical option to treat high-risk patients with severe aortic stenosis or aortic regurgitation. PMID- 28992964 TI - When in doubt, look to see what works in nature. PMID- 28992965 TI - Can we live without P values? The answer. PMID- 28992966 TI - To bleed or not to bleed? That is the question. PMID- 28992967 TI - Aortopexy for left pulmonary vein obstruction. PMID- 28992968 TI - Functional survival: Alive and better. PMID- 28992969 TI - Serial images demonstrating progression of type A intramural hematoma to type B aortic dissection. PMID- 28992970 TI - Can robot-assisted mitral repairs be super good? PMID- 28992971 TI - Diabetes mellitus adversely affects mortality and recurrence after valve surgery for infective endocarditis. AB - BACKGROUND: Although diabetes mellitus (DM) increases the incidence of infective endocarditis (IE), little is known about the outcome of valve surgery for active IE in patients with DM. We evaluated the clinical outcomes of valve surgery for IE in patients with DM. METHODS: Between 2009 and 2016, 470 patients underwent valve surgery for definitive left-sided active IE at 12 affiliated hospitals. We compared the preoperative variables and clinical outcomes between patients without (n = 374) and with DM (n = 96). RESULTS: Staphylococcus and chronic hemodialysis were more prevalent in patients with DM, and these patients had greater preoperative inflammation levels and worse renal function than patients without DM. In-hospital mortality was 8% in patients without DM and 13% in patients with DM (P = .187). The overall survival rate at 1 and 5 years was 87% and 81% in patients without DM and 72% and 59% in patients with DM (P < .001). The incidence of infection-related death was greater in patients with DM than in patients without DM (P < .001; hazard ratio 3.74 [1.78-7.71]). Freedom from the recurrence of endocarditis at 1 and 5 years postoperatively was 98% and 95% in patients without DM, and 89% and 78% in patients with DM (P < .001), respectively. The Cox hazard analysis revealed that the presence of DM was the only independent risk for recurrence (hazard ratio 3.74 [1.45-9.54], P = .007). CONCLUSIONS: The short- and mid-term outcome after valve surgery for active IE in patients with DM is worse because of the greater prevalence of infection-related death and IE recurrence. PMID- 28992972 TI - Atrioventricular valve regurgitation in patients undergoing total cavopulmonary connection: Impact of valve morphology and underlying mechanisms on survival and reintervention. AB - OBJECTIVE: The study objective was to determine the mechanisms of atrioventricular valve regurgitation in single-ventricle physiology and their influence on outcomes after total cavopulmonary connection. METHODS: Among 460 patients who underwent a total cavopulmonary connection, 101 (22%) had atrioventricular valve surgery before or coincident with total cavopulmonary connection. RESULTS: Atrioventricular valve morphology showed 2 separated in 33 patients, mitral in 11 patients, tricuspid in 41 patients, and common in 16 patients. Patients with a tricuspid and a common atrioventricular valve underwent atrioventricular valve surgery frequently, 27% and 36%, respectively. Atrioventricular valve regurgitation was due to 1 or more of the following mechanisms: dysplastic leaflet (62), prolapse (53), annular dilation (27), cleft (22), and chordal anomaly (14). Structural anomalies were observed in 89 patients (88%). The procedure was atrioventricular valve repair in 81 patients, atrioventricular valve closure in 16 patients, and atrioventricular valve replacement in 4 patients. Among 81 patients who underwent initial repair, repeat repair was required in 20 patients, atrioventricular valve replacement was required in 7 patients, and atrioventricular valve closure was required in 3 patients. Among patients undergoing atrioventricular valve surgery, overall survival after total cavopulmonary connection (88% vs 95% at 15 years, P = .01), freedom from atrioventricular valve reoperation after total cavopulmonary connection (75% vs 99% at 15 years, P < .01), and grade of atrioventricular valve regurgitation at a median follow-up of 6.6 years (P < .01) were worse than in those who did not require atrioventricular valve surgery. CONCLUSIONS: Atrioventricular valve regurgitation in univentricular heart is more frequently associated with a tricuspid or a common atrioventricular valve, and structural anomalies are the primary cause. Significant atrioventricular valve regurgitation requiring surgery influences survival after total cavopulmonary connection, especially when atrioventricular valve replacement was needed. Surgical management based on mechanisms of regurgitation is mandatory. PMID- 28992973 TI - Rivaroxaban ameliorates disease course in an animal model of multiple sclerosis. AB - Recent studies have implicated an important role for coagulation factors in neuroinflammatory disorders like multiple sclerosis (MS). Here, we investigate the role of factor X (FX) in neuroinflammation by using rivaroxaban the selective inhibitor of activated FX (FXa) in experimental autoimmune encephalomyelitis (EAE, an animal model of MS). Rivaroxaban-treated rats were less susceptible to EAE compared to the untreated control group. This finding was accompanied by reduced T-cell infiltration and microglia activation. Our study identifies FX as a possible target in neuroinflammatory diseases. As FXa inhibitors are approved for other disorders, FXa blockade could serve as a fast available medication. PMID- 28992974 TI - Diazepam treatment reduces inflammatory cells and mediators in the central nervous system of rats with experimental autoimmune encephalomyelitis. AB - Benzodiazepines are psychoactive drugs and some of them also affect immune cells. We here characterized the inflammatory and infiltrating immune cells in the central nervous system (CNS) during the acute phase of experimental autoimmune encephalomyelitis (EAE) in animals treated with Diazepam. Also, we evaluated the expression of Translocator Protein (18kDa) (TSPO), which is a biomarker of neuroinflammatory diseases. The results indicate that Diazepam exerts protective effects on EAE development, decreasing the incidence of the disease and reducing the number of inflammatory cells in CNS, with a concomitant decrease of TSPO levels in brain tissue and CNS inflammatory CD11b+ cells. PMID- 28992976 TI - A Mixed Methods Evaluation of the Feasibility and Acceptability of an Adapted Cardiac Rehabilitation Program for Home Care Patients. AB - Home care clinicians have an opportunity to improve care for post-hospitalization patients with cardiovascular disease. This mixed methods study examined the feasibility and acceptability of an adapted cardiac rehabilitation (CR) program for the home care setting. Surveys measuring patient self-care and knowledge were administered to patients (n = 46) at baseline and at 30-day follow-up. Semi structured interviews were conducted with patients (n = 28) and home care clinicians (n = 11) at completion of the program. All survey indicators demonstrated a trend towards improvement, with a statistically significant increase in the self-care management subscale (p = 0.002). Qualitative analyses identified three patient themes (self-awareness, nutrition, motivation) and three clinician themes (systematic approach, motivation, patient selection process). Incorporating CR into the home care setting proved to be a feasible and acceptable approach to increasing access to CR services among elderly patients. PMID- 28992977 TI - Special Issue on Social Determinants of Health. PMID- 28992975 TI - A prospective, placebo controlled study on the humoral immune response to and safety of tetanus revaccination in myasthenia gravis. AB - OBJECTIVE: To investigate the humoral immune response to and safety of a tetanus revaccination in patients with myasthenia gravis or Lambert-Eaton myasthenic syndrome. METHODS: A tetanus revaccination was administered to 66 patients. Before and 4weeks after revaccination a blood sample and clinical outcome scores were obtained. Anti-tetanus IgG total, IgG1 and IgG4 titres were measured with an ELISA and disease-specific antibody titres (AChR, MuSK or VGCC) with a radio immunoprecipitation assay. A historic healthy control group was used for comparing tetanus antibody titres with that of our patients. A placebo (saline) vaccination group was used to investigate the variability of clinical outcome scores with a 4weeks interval. RESULTS: In 60 of 65 patients, a significant increase of the anti-tetanus antibody response was measured. Thymectomy did not have an impact on this responsiveness. Patients with immunosuppressive medication had a significantly lower pre and post titre compared to healthy controls, but their response was still significant. The titres of disease-specific antibodies were unchanged 4weeks after revaccination. The clinical outcome scores showed no exacerbation of symptoms of the disease. CONCLUSION: A tetanus revaccination in patients with myasthenia gravis or Lambert-Eaton myasthenic syndrome is safe and induces a significant immune response, irrespectively of their immunosuppressive medication. We observed neither immunological nor clinical relevant exacerbations associated with the tetanus revaccination. CLINICAL TRIAL REGISTRY: The tetanus trial is listed on clinicaltrialsregister.eu under 2014-004344-35. The placebo AChR MG group was part of another clinical trial, investigating influenza vaccination in myasthenic patients. This trial is listed on clinicaltrialsregister.eu under 2016-003138-26. PMID- 28992978 TI - Quantification of Prostate-Specific Antigen determination in usual clinical practice. PMID- 28992979 TI - Hypoparathyroidism and disorder of sex development: A rare association. PMID- 28992980 TI - Adherence to recommendations of the Therapeutic Positioning Report about treatment with oral anticoagulants in elderly patients with atrial fibrillation. The ESPARTA study. AB - BACKGROUND AND OBJECTIVE: To evaluate the adherence to the recommendations in clinical practice performed by the Therapeutic Positioning Report (TPR) of the Spanish Agency of Medicines and Sanitary Products about the treatment with oral anticoagulants in patients aged>=75 years old with nonvalvular atrial fibrillation (NVAF) treated in Internal Medicine departments in Spain. PATIENTS AND METHODS: Observational, cross-sectional and multicenter study in which 837 patients aged>=75 years old with NVAF, with stable treatment with oral anticoagulants at least 3 months before inclusion, and that had started treatment with oral anticoagulants before the inclusion period were included. RESULTS: Mean age was 83.0+/-5.0 years old, mean CHADS2 score 3.2+/-1.2, mean CHA2DS2-VASc score 5.0+/-1.4, and mean HAS-BLED score 2.1+/-0.9. A percentage of 70.8 of patients were treated with vitamin K antagonists (VKA) and the rest of patients with direct oral anticoagulants (DOACs). A percentage of 65.6 of patients treated with VKA did not follow the recommendations made by the TPR compared with 43.0% of patients treated with DOACs (P<.0001). In the case of VKA, the main reason for being considered as not appropriate according to the TPR was having poor control of anticoagulation and not switching to DOACs, whereas in the case of DOACs, it was not receiving the adequate dose according to the TPR. CONCLUSIONS: In a high proportion of anticoagulated elderly patients with NVAF in Spain, the recommendations performed by the TPR are not followed, particularly with VKA, since patients are not switched to DOACs despite time in therapeutic range. PMID- 28992981 TI - Extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae from urinary tract infections: Evolution of antimicrobial resistance and treatment options. AB - BACKGROUND AND OBJECTIVES: A study of the susceptibility to antimicrobials of the extended spectrum beta-lactamase phenotypes (ESBL) in Escherichia coli and Klebsiella spp. was performed to discover the evolution of this type of resistance from urinary tract infections. MATERIAL AND METHOD: A retrospective study was carried out between 2012 and 2016. Susceptibility to ciprofloxacin, tobramycin, cefoxitin, fosfomycin, nitrofurantoin, co-trimoxazole, and carbapenems was analyzed using MicroScan(r) system. RESULTS: A total of 95,399 samples were processed and 9,772 E. coli, 1,784 Klebsiella pneumoniae and 248 Klebsiella oxytoca were isolated. ESBL strains were more frequent in women, although they decreased during 2015 and 2016 (65.7-67.2%). The prevalence of K. pneumoniae ESBL increased annually (28.1% in 2016). The average prevalence of E. coli ESBL was 10.5% with few oscillations. Higher resistance occurred to ciprofloxacin and cotrimoxazole, 89.5 and 94.7% in 2015, respectively, and there was lesser resistance to imipenem. Fosfomycin and nitrofurantoin were very active on E. coli ESBL. CONCLUSIONS: ESBL producing E. coli and K. pneumoniae were prevalent, especially the latter, with a significant resistance to ciprofloxacin and cotrimoxazole. Susceptibility to imipenem was high. PMID- 28992982 TI - Associated factors with depressive symptoms in patients with Parkinson's disease. PMID- 28992983 TI - Primary hyperparathyroidism. AB - Primary hyperparathyroidism (PHPT) is a common endocrinological process, characterized by chronic elevation of serum concentrations of calcium and parathyroid hormone (PTH). Many years ago, the most frequent forms of clinical presentation were symptomatic renal or skeletal disease with moderate or severe hypercalcemia; however, currently, most patients have few symptoms and mild hypercalcemia. A new form of presentation called normocalcemic PHPT has also been described but clinical consequences are not well established. The biochemical profile of PHPT is characterized by hypercalcemia and high or inappropriately normal PTH concentrations. Parathyroidectomy is the only definitive cure. Medical treatment with the calcimimetic cinacalcet has been shown to normalize calcemia in a high percentage of cases. PMID- 28992984 TI - Avoidable hospitalizations due to adverse drug reactions in an acute geriatric unit. Analysis of 3,292 patients. AB - OBJECTIVE: To determine prevalence of admissions due to an adverse drug reaction (ADR) and determine whether or not admission was avoidable, and what drugs and risk factors were implicated. DESIGN: Cross-sectional observational study. STUDY SAMPLE: All patients hospitalized in an acute geriatric unit during the period January 2001 to December 2010 were studied. MEASUREMENT: To determine whether admissions were due toADR, we used the World Health Organization-Uppsala Monitoring Centre criteria and the Naranjo scale. Beers criteria were used to detect potentially inappropriate medication. RESULTS: A total of 3,292 patients (mean age 84.7 years, 60.1% women) were studied. Of these, 197 (6%) were admissions for ADR and nearly three quarters (76.4%, 152 cases) were considered avoidable admissions. The 5 most frequent drugs associated with admissions for ADR were digoxin, nonsteroidal anti-inflammatory drugs, benzodiazepines, diuretics and antibiotics. Independent risk factors for admissions for ADR were being female (OR 1.84; 95% CI 1.30-2.61), inappropriate medication according to Beers criteria (OR 4.20; 95% CI 2.90-6.03), polypharmacy (>5 drugs) (OR 1.50; 95% CI 1.04-2.13), glomerular filtration rate<30mL/min (OR 3; 95% CI 2.12-4.23) and sedative use (OR 1.40; 95% CI 1-1.91). CONCLUSION: ADR were responsible for 6% of admissions to an acute geriatric unit, and over 75% of these admissions were considered avoidable. Associated risk factors were being female, inappropriate medication, polypharmacy, renal insufficiency and sedative use. PMID- 28992985 TI - APOA1 and APOB polymorphisms and apolipoprotein concentrations as biomarkers of risk in acute coronary syndrome: Relationship with lipid-lowering therapy effectiveness. AB - BACKGROUND AND OBJECTIVE: Lipid metabolism alterations contribute to acute coronary syndrome (ACS). rs670, rs5070 and rs693 polymorphisms have shown to modify the risk of cardiovascular disease. Apolipoprotein A-I (ApoA-I) plays a major role in reverse cholesterol transport; apolipoprotein B (ApoB) contributes to accumulation of cholesterol in the plaque. The aim of this study was to investigate the association of rs670 and rs5070 polymorphisms of APOA1 and rs693 polymorphism of APOB with ACS and circulating levels of its proteins and find if ApoB/ApoA-I could be implemented as an independent parameter of risk for cardiovascular disease and as a biomarker of lipid-lowering therapy effectiveness in Mexican population. METHODS: Three hundred patients with ACS and 300 control subjects (CS) were included. RESULTS: Neither genotype nor allele frequencies of rs670, rs5070 and rs693 polymorphisms showed statistical differences between groups. Serum levels of ApoA-I (195 vs. 161.4mg/dL; P<.001) and ApoB (167 vs. 136.9mg/dL; P<.001) were significantly higher in CS compared with ACS; however, there was no genetic association. Unstable angina patients showed the highest ApoA-I levels (males: 176.3mg/dL; females: 209.1mg/dL). CONCLUSION: The rs670, rs5070 and rs693 polymorphisms are not genetic susceptibility factors for ACS in Mexican population and had no effect on their apolipoprotein concentrations. In our population, ApoA-I, ApoB and HDL-C could be better biomarkers of cardiovascular risk and could indicate if statins doses reduce atherogenic particles properly. PMID- 28992986 TI - Pros and cons of vaccination against serogroup B meningococcal disease. AB - A vaccine has recently been approved in the EU against meningococcal serogroup B, the main cause of meningococcal disease. There is a fierce debate about the decision regarding a universal vaccination in infants older than 2 months, as recommended by the majority of scientific societies. In western Europe the only country to have included the universal vaccination is the United Kingdom, with a lower incidence of the disease than Ireland. Other countries have also adopted it, such as the Czech Republic, Cuba and certain regions of Italy. Numerous cost effectiveness studies have been published regarding the vaccination with different assumptions, which have supported the decision not to implant the universal vaccination because it exceeds the will to pay for a health benefit. We discuss the pros and cons of the universal vaccination against meningococcal B, recommended by the Sociedad Espanola de Pediatria (Spanish Society of Paediatrics), which as yet has not been implemented. PMID- 28992988 TI - Study of the influence of surfactants on the activity coefficients and mass transfer coefficients of methanol in aqueous mixtures by reversed-flow gas chromatography. AB - This work focuses on the influences of surfactants on the activity coefficients, gamma, of methanol in binary mixtures with water, as well as on the mass transfer coefficients, kc, for the evaporation of methanol, which is a ubiquitous component in the troposphere, from mixtures of methanol with water at various surfactant's and methanol's concentrations. The technique used is the Reversed Flow Gas Chromatography (R.F.G.C.), a version of Inverse Gas Chromatography, which allows determining both parameters by performing only one experiment for the kc parameter and two experiments for the gamma parameter. The kc and gamma values decrease in the presence of the three surfactants used (CTAB, SDS, TRITON X-100) at all methanol's and surfactant's concentrations. The decrease in the methanol's molar fraction, at constant number of surfactant films leads to a decrease in the kc and gamma values, while the decrease in the surfactant's concentration, at constant methanol's molar fraction leads to an increase in both the kc and gamma parameters. Mass transfer coefficients for the evaporation of methanol at the surfactant films, are also calculated which are approximately between 4 and 5 orders of magnitude larger than the corresponding mass transfer coefficients at the liquid films. Finally, thicknesses of the boundary layer of methanol in the mixtures of methanol with water were determined. The quantities found are compared with those given in the literature or calculated theoretically using various empirical equations. The precision of the R.F.G.C. method for measuring gamma and kc parameters is approximately high (94.3-98.0%), showing that R.F.G.C. can be used with success not only for the thermodynamic study of solutions, but also for the interphase transport. PMID- 28992987 TI - The resting perfusion pattern associates with functional decline in type 2 diabetes. AB - We investigated the relationships between cerebral blood flow (CBF), cognitive, and mobility decline in type 2 diabetes mellitus (T2DM) over a 2-year period. Seventy-three participants (41 T2DM and 32 controls) were evaluated using volumetric CBF with arterial spin labeling perfusion magnetic resonance imaging at baseline and at the 2-year follow-up. Regions with significant CBF differences between T2DM participants and controls at baseline were detected using voxel-wise analysis. Correlation analysis was performed to investigate the association between regional CBF and cognitive or mobility performance over the 2-year span. Compared to controls, participants with T2DM had decreased CBF in the resting state default mode, visual, and cerebellum networks. Greater decrease in longitudinal CBF values at these regions over a 2-year span was associated with worse gait, memory and executive functions, and higher baseline insulin resistance and worse baseline cognitive performance. In T2DM, impairment of resting regional perfusion is closely related to worse cognitive and mobility performance. Insulin resistance may further contribute to regional perfusion deficit in T2DM. PMID- 28992989 TI - Fully compatible and ultra-sensitive micellar electrokinetic chromatography tandem mass spectrometry using sheathless porous-tip interfacing. AB - The on-line coupling of micellar electrokinetic chromatography and mass spectrometry (MEKC-MS) is often hampered by incompatibility problems leading to reduced separation performance and unfavorable limits of detection (LODs). Here we propose a new selective and highly sensitive MEKC-MS/MS method employing a sheathless porous-tip interface in combination with a micellar phase comprised of semi-volatile surfactant molecules. Carbamate pesticides (CRBs) were selected as representative model compounds being neutral toxic pollutants potentially present at trace levels in environmental water samples. A background electrolyte of 75mM perfluorooctanoic acid adjusted to pH 9.0 with ammonium hydroxide allowed efficient separation of 15 CRBs and appeared fully compatible with electrospray ionization (ESI)-MS. Interfacing parameters, such as the distance between the capillary tip and mass-spectrometer inlet, ESI voltage, and dry gas temperature and flow were optimized in order to attain good spray stability and high analyte signal-to-noise ratios. For CRBs the LODs ranged from 0.2 to 3.9ngL-1 (13nL injected, i.e., 2% of capillary volume), representing an improvement for certain CRBs of more than 300-fold when compared with conventional sheath-liquid interfacing. Good linearity (R2>0.99) and satisfactory reproducibility were obtained for all CRBs with interday RSD values for peak area and migration time of 4.0-11.3% and below 1.5%, respectively. Analysis of spiked mineral water showed that the new MEKC-MS/MS method allows selective and quantitative determination of CRB concentrations below the maximum residue limit of 100ngL-1 without the need for sample preconcentration. PMID- 28992990 TI - One-step targeted accumulation and detection of camptothecin analogues from fruits of Camptotheca acuminata Decne using bilayer solid-phase extraction coupled with ultra-high-performance liquid chromatography-tandem mass spectrometry. AB - Camptothecins, a kind of monoterpene-quinoline alkaloids from Camptotheca acuminata Decne, have long attracted much attention worldwide as an anti-cancer drug. However, there is still a lack of effective methods for the accumulation and discovery of camptothecin analogues from botanic resources for camptothecin based drug research. This work develops a one-step method for the targeted accumulation, quick detection, and identification of camptothecin analogues from C. acuminata fruit using bilayer solid-phase extraction coupled with ultra-high performance liquid chromatography-tandem mass spectrometry (bilayer-SPE-UHPLC-Q TOF-MS/MS). The bilayer-SPE cartridge, with polyamide (PA) as the upper layer and octadecyl silane (ODS) as the lower layer, was designed for the removal of flavonoid and ellagic acid impurities and the enrichment of camptothecins for further MS analysis. Subsequently, the mass spectrometry fragmentations, especially multistage retro-Diels-Alder cleavage, were summarized based on the MS/MS data of 10 reference camptothecins. The UHPLC-Q-TOF-MS/MS conditions were optimized, and the MS/MS data of the potential camptothecin analogues in the bilayer-SPE enriched fractions were analyzed. A total of 30 camptothecin analogues, including 15 new compounds, were identified from the fruit according the fragmentation pathways of the reference standards. The proposed structure of peak 20 was confirmed using its NMR data through rapid enrichment and purification. Overall, the bilayer-SPE enrichment and reliable mass spectrometry fragmentation in our work could provide an effective and simple method for the exploration of the biosynthesis pathway and metabolomics of camptothecin analogues. PMID- 28992991 TI - Comprehensive two-dimensional gas chromatography for biogas and biomethane analysis. AB - The gas industry is going to be revolutionized by being able to generate bioenergy from biomass. The production of biomethane - a green substitute of natural gas - is growing in Europe and the United-States of America. Biomethane can be injected into the gas grid or used as fuel for vehicles after compression. Due to various biomass inputs (e.g. agricultural wastes, sludges from sewage treatment plants, etc.), production processes (e.g. anaerobic digestion, municipal solid waste (MSW) landfills), seasonal effects and purification processes (e.g. gas scrubbers, pressure swing adsorption, membranes for biogas upgrading), the composition and quality of biogas and biomethane produced is difficult to assess. All previous publications dealing with biogas analysis reported that hundreds of chemicals from ten chemical families do exist in trace amounts in biogas. However, to the best of our knowledge, no study reported a detailed analysis or the implementation of comprehensive two-dimensional gas chromatography (GC*GC) for biogas matrices. This is the reason why the benefit of implementing two-dimensional gas chromatography for the characterization of biogas and biomethane samples was evaluated. In a first step, a standard mixture of 89 compounds belonging to 10 chemical families, representative of those likely to be found, was used to optimize the analytical method. A set consisting of a non-polar and a polar columns, respectively in the first and the second dimension, was used with a modulation period of six seconds. Applied to ten samples of raw biogas, treated biogas and biomethane collected on 4 industrial sites (two MSW landfills, one anaerobic digester on a wastewater treatment plant and one agricultural biogas plant), this analytical method provided a "fingerprint" of the gases composition at the molecular level in all biogas and biomethane samples. Estimated limits of detection (far below the MUgNm-3) coupled with the resolution of GC*GC allowed the comparison of the real samples considered. This first implementation of GC*GC for the analysis of biogas and biomethane demonstrated unambiguously that it is a promising tool to provide a "fingerprint" of samples, and to monitor trace compounds by families. PMID- 28992992 TI - Corrigendum to "Bone Morphogenetic Protein (BMP) signaling in animal reproductive system development and function" [Dev. Biol. 427(2) (2017) 258-269]. PMID- 28992993 TI - Risk prediction model for in-hospital mortality in women with ST-elevation myocardial infarction: A machine learning approach. AB - BACKGROUND: Studies had shown that mortality due to ST-elevation myocardial infarction (STEMI) is higher in women compared with men. The purpose of this study is to develop and validate prediction models for all-cause in-hospital mortality in women admitted with STEMI using logistic regression and random forest, and to compare the performance and validity of the different models. METHODS: Data from the National Inpatient Sample (NIS) data years 2011-2013 were used to identify women admitted with STEMI. The main outcome was all-cause in hospital mortality. Patients were divided into development and validation cohorts, and trained models were internally validated using 20% of the 2012 data, and externally validated using 2011 and 2013 NIS data. RESULTS: Three main models were developed and compared; multivariate logistic regression, full and reduced random forest models. In the multivariate logistic regression, 11 variables were included in the final model based on backward elimination. The full random forest model contained 32 variables, and the reduced model contained 17 variables selected based on individual variable importance. In the internal validation cohort, the C-index was 0.84, 0.81, and 0.80 for the multivariate logistic regression, full, and reduced random forest models, respectively. The models showed good stability in the external validation cohorts with a C-index for the logistic regression, full, and reduced random forest models of 0.84, 0.85, and 0.81 for year 2011, and 0.82, 0.81, and 0.81 for year 2013, respectively. CONCLUSIONS: Random forest was comparable to logistic regression in predicting in hospital mortality in women with STEMI, and can be a useful and accurate tool in clinical practice. PMID- 28992994 TI - Erratum to "Ethnic density, immigrant enclaves, and Latino health risks: A propensity score matching approach" [Soc. Sci. Med. 189 (2017) 44e52]. PMID- 28992995 TI - Transfer of radionuclides to plants of natural ecosystems at the Semipalatinsk Test Site. AB - A systematic study devoted to 137Cs, 90Sr, 241Am, 239+240Pu radionuclides in vegetation cover from several spots of the Semipalatinsk test site (STS) is summarised in this paper, highlighting the main findings obtained. The analysed spots are characterized by various types of radioactive contamination. Transfer factors (Tf) required for the quantitative description of the radionuclides transition from the soil to aboveground plant parts were determined, being found that, on average, the minimum Tf for all the radionuclides concerned were determined on the "Experimental Field" ground, followed by the determined ones in the "plumes" of radioactive fallout and in the conditionally "background" territories analysed. The highest transfer factors were characteristic of zones of radioactive streamflows and places of warfare radioactive agent (WRA) tests. On the other hand, ordering the radionuclide transferring factors in descending order, the following sequence was obtained: 90Sr Tf > Cs Tf > 239+240Pu Tf > 241Am Tf, with the 90Sr Tf, on the average, exceeding the 137Cs Tf by 8 times and exceeding the 239+240Pu Tf by up 16 times. 239+240Pu Tf values were up to 3 times higher than the 241Am Tf. The exception to the indicated radionuclide Tf descending order corresponded to places of WRA tests where Tf of radionuclides of interest by plants follows the sequence 90Sr > 239+240Pu > 137Cs. PMID- 28992996 TI - Attention profiles in childhood absence epilepsy compared with attention deficit/hyperactivity disorder. AB - OBJECTIVE: This study aimed to compare the attention profiles of subjects with childhood absence epilepsy (CAE) to those of children with attention deficit/hyperactivity disorder (ADHD) and controls. METHOD: We retrospectively reviewed the medical records of 20 children (age 7.2 +/- 1.6 years, 5 boys) in whom CAE was diagnosed at the Department of Pediatric Neurology of Asan Medical Center, Seoul, Korea. ADHD and control subjects were selected from children who visited the Department of Pediatric Psychiatry and were confirmed as having or not having ADHD based on Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and the Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime version (K-SADS-PL). The 20 children with CAE, 20 with ADHD and 20 controls completed the Advanced Test of Attention (ATA), which is a computerized continuous performance task. RESULTS: The CAE subjects without ADHD showed increased Omission errors (p=.013) on the visual ATA and Response time (p=0.044) on the auditory ATA than the controls, although these differences did not remain significant after multiple comparison correction. The CAE subjects without ADHD had significantly decreased Response time variability on the visual ATA than the ADHD group (p<0.001). The CAE subjects with comorbid ADHD showed increased Commission errors (p=0.020) and Response time variability (p=0.016) on the visual ATA and increased Commission errors (p=0.022) on the auditory ATA than the CAE subjects without ADHD, although statistical significance disappeared after multiple comparison adjustments. CONCLUSION: These findings suggest that selective attention is impaired in children with CAE and comorbid ADHD contributes to further impairment of sustained attention and response inhibition. PMID- 28992997 TI - Association of Tibial Plateau Fracture Morphology With Ligament Disruption in the Context of Multiligament Knee Injury. AB - BACKGROUND: We identified common morphologies of tibial plateau fractures that arise with multiligament knee injuries (MLKIs), and investigated the relationship of the fracture with ligament tears. We also evaluated the correlation of 3 tibial plateau fracture classification systems (Schatzker, AO, and Duparc). METHODS: Over a 2-year period, a single orthopaedic surgeon at our institution managed 90 MLKIs. Images of those knees with a tibial plateau fracture were retrospectively reviewed and classified per Schatzker, AO, and Duparc systems. Correlation among the 3 systems was evaluated using Spearman nonparametric correlation coefficient. Associations between fracture grading system and ligament tears were estimated using logistic regression. Associations between ligament tears and tibial plateau fracture location (medial vs lateral) were estimated using exact logistic regression. RESULTS: A total of 19 of 90 knees suffered tibial plateau fractures. There was reasonable correlation among the 3 tibial plateau classification systems. Increasing grade under the Schatzker system showed statistically significant associations with medial collateral ligament (MCL) (P = 0.056) and posterolateral corner (PLC) (P = 0.035) tears. Increasing grade under the Duparc system showed statistically significant associations with MCL (P = 0.032) and PLC (P = 0.058) tears. PLC tears had a statistically significant association with medial plateau fractures (P = 0.003); odds ratio of 121.1 (95% CI: 2.2-infinity). MCL tears had a statistically significant association with lateral plateau fractures (P = 0.004); odds ratio of 18.4 (95% CI: 2.1-infinity). Although not statistically significant, 8 out of 9 knees with a lateral plateau fracture demonstrated tear of the anterior cruciate ligament (ACL). CONCLUSIONS: As the grade of designation increases within the Schatzker and Duparc tibial plateau fracture classifications, as does the likelihood of MCL and PLC tear. The majority of tibial plateau fractures that occur in the context of MLKI are either isolated to the medial or lateral tibial plateau. Medial tibial plateau fractures are associated with PLC tears. Lateral tibial plateau fractures are associated with MCL tears, and although not statistically significant in our small sample size, 8 out of 9 knees also demonstrated a tear of the ACL. PMID- 28992998 TI - Predictive value of depression and anxiety for long-term mortality: differences in outcome between acute coronary syndrome and stable angina pectoris. AB - BACKGROUND: Since the early 2000s the treatment of choice for an acute myocardial infarction has moved from thrombolytic therapy to primary PCI (pPCI). As a result, the majority of patients undergoing PCI shifted from stable angina pectoris (SA) to acute coronary syndrome (ACS). Additionally the previously observed association between depression and anxiety and long-term outcome in patients who underwent a PCI may have been changed. The main objective of this study was to investigate the predictive value of depression and anxiety for 10 year mortality, in a cohort with post-PCI patients treated for SA versus patients treated for ACS. METHODS: This prospective single center cohort consists of a consecutive series of patients (n=528) treated with PCI. At 1month post-PCI, patients completed the Dutch version of the Hospital Anxiety and Depression Scale (HADS). RESULTS: After adjustment for baseline characteristics depression was associated with higher 10-year mortality post-PCI (HR 1.58 95% Confidence Interval [95% CI] 1.04-2.40). In the ACS population no association between depression and 10-year mortality was found (HR 1.05 95% CI 0.62-1.79), in contrast to the SA population (HR 1.97 95% CI 1.09-3.57). After additional adjustment for anxiety, depression was no longer associated with higher mortality. CONCLUSIONS: Anxiety at baseline was associated with an increased 10 year mortality rate after PCI. Depression was also associated with higher 10-year mortality, however the association disappeared after additional adjustment for anxiety. This finding was more pronounced in patients presenting with SA as compared to those presenting with ACS, which might be a result of the increasing number of ACS patients treated with pPCI. PMID- 28992999 TI - Provisional versus elective two-stent strategy for unprotected true left main bifurcation lesions: Insights from a FAILS-2 sub-study. AB - BACKGROUND: This study sought to investigate the optimal percutaneous coronary intervention (PCI) strategy for true unprotected left main coronary artery (ULMCA) bifurcations. METHODS: The FAILS-2 was a retrospective multi-center study including patients with ULMCA disease treated with second-generation drug-eluting stents. Of these, we compared clinical outcomes of a provisional strategy (PS; n=216) versus an elective two-stent strategy (E2S; n=161) for true ULMCA bifurcations. The primary endpoint was the incidence of major adverse cardiac events (MACEs) at 3-years. We further performed propensity-score adjustment for clinical outcomes. RESULTS: There were no significant differences between the groups in terms of patient and lesion characteristics. 9.7% of patients in the PS group crossed over to a provisional two-stent strategy. MACEs were not significantly different between groups (MACE at 3-year; PS 28.1% vs. E2S 28.9%, adjusted p=0.99). The rates of target lesion revascularization (TLR) on the circumflex artery (LCX) were numerically high in the E2S group (LCX-TLR at 3 years; PS 11.8% vs. E2S 16.6%, adjusted p=0.51). CONCLUSIONS: E2S was associated with a comparable MACE rate to PS for true ULMCA bifurcations. The rates of LCX TLR tended to be higher in the E2S group although there was no statistical significance. CONDENSED ABSTRACT: This study sought to compare the clinical outcomes of a provisional strategy (PS) with an elective two-stent strategy (E2S) for the treatment of true unprotected left main coronary artery bifurcations. 377 Patients (PS 216 vs. E2S 161 patients) were evaluated, and 9.7% in the PS group crossed over to a two-stent strategy. E2S was associated with a similar major adverse cardiac event rate at 3-years when compared to the PS strategy (PS 28.1% vs. E2S 28.9%, p=0.99). However, the left circumflex artery TLR rate at 3-year tended to be higher in the E2S group (PS 11.8% vs. E2S 16.6%, p=0.51). PMID- 28993000 TI - Incidence and impact of renal dysfunction on clinical outcomes after transcatheter aortic valve implantation. AB - BACKGROUND: The impact of baseline renal dysfunction on early and late clinical outcomes after transcatheter aortic valve implantation (TAVI) remains to be defined. METHODS: 927 patients included in the prospective Bern TAVI registry were classified on the basis of the baseline estimated glomerular filtration rate (eGFR), as having none or mild (eGFR >=60mL/min/1.73m2, n=284, 30.6%), moderate (eGFR between 30 and 59mL/min/1.73m2, n=535, 57.7%) and severe (eGFR <30mL/min/1.73m2, n=108, 11.7%) renal dysfunction. RESULTS: A graded relationship between stages of renal dysfunction and increasing risk profile was observed with higher STS score and lower left ventricular ejection fraction among patients with eGFR<30 (p<0.001 across groups). In patients with none or mild, moderate, and severe renal dysfunction the rate of all-cause mortality was 1.8%, 5.2% and 8.3% at 30-day and 11.0%, 15.0% and 19.5% at 1-year, respectively. After adjusting for relevant confounders, severe renal dysfunction was associated with an increased risk of cardiovascular death (adjusted Hazard Ratio, HRadj, 3.90, 95% Confidence Interval, CI 1.15-13.2) and stage 3 acute kidney injury (HRadj 5.15, 95% CI 1.72 15.5) at 30-day follow-up, however no significant association was found for clinical outcomes at 1-year follow-up. Moreover, moderate and severe renal dysfunction were found to be associated with bleeding at 1-year follow-up (HRadj, 1.36, 95% CI 1.04-1.78 and HRadj 1.49, 95% CI 1.00-2.21, respectively). CONCLUSIONS: Pre-procedural renal dysfunction differentially affects early clinical outcomes, although the magnitude of this association is diluted over time by the overriding effect of underlying risk and comorbidities. PMID- 28993001 TI - Absence of adventitial vasa vasorum formation at the coronary segment with myocardial bridge - An optical coherence tomography study. AB - BACKGROUND: Myocardial bridge (MB) is a myocardial bundle through which coronary segment tunnels and could compress coronary arteries causing myocardial ischemia. However, the characteristic structural findings of MB remain to be fully elucidated. Recently, we demonstrated that optical coherence tomography (OCT) enables us to visualize adventitial vasa vasorum (VV) formation in humans. In this study, we examined adventitial VV formation at the coronary segment with MB in humans using OCT. METHODS: We examined 15 consecutive patients with suspected angina pectoris and MB in the left anterior descending (LAD) coronary arteries but no angiographic coronary stenosis. MB was detected on coronary angiography as a segment with milking effect. We performed intracoronary OCT imaging along the entire LAD. Morphometric analysis was performed at MB and proximal/distal segments at every 1mm. RESULTS: OCT examination showed the absence of adventitial VV formation at MB in the LAD, while VV was clearly noted at both the proximal and distal reference segments. Adventitial VV area was significantly less at MB compared with the proximal or distal references. CONCLUSIONS: These results with OCT imaging indicate that coronary segments with MB lack adventitial VV formation in humans, suggesting that MB could influence morphological and functional changes of the coronary artery. PMID- 28993002 TI - Recovery patterns over 4 years after distal radius fracture: Descriptive changes in fracture-specific pain/disability, fall risk factors, bone mineral density, and general health status. AB - STUDY DESIGN: Descriptive/Longitudinal cohort. INTRODUCTION: Distal radius fracture (DRF) is a common fall related fragility fracture that is known to be an early and independent predictor of secondary osteoporotic (OP) fractures. Changes in falls risk status, bone status and general health has not been evaluated prospectively in a population that has sustained a DRF. PURPOSE OF THE STUDY: The purpose of our study was to describe the status of fracture-specific pain/disability, fall risk factors such as physical activity (PA) and fear of falling (FOF), bone mineral density (BMD) and general health status (HS) in people with a DRF and how these variables change over four years with respect to sex, age, incidence of secondary falls and secondary OP fractures. METHODS: Patients (n = 94) self-reported their fracture-specific pain and disability (Patient-Rated Wrist Evaluation), PA (Rapid Assessment of Physical Activity), FOF (Modified Fall Efficacy Scale), HS (12-item Short Form Health Survey) and completed dual-energy X-ray absorptiometry scan based BMD assessment (lumbar spine and total hip) at baseline (1-2 weeks post-fracture), six months and four years after DRF. Descriptive statistics and general linear models were used to describe changes in recovery patterns over four years. RESULTS: There was significant (p<0.001) improvement in fracture-specific pain/disability (60 points), FOF (1 point) and physical HS (11 points) between baseline and 4 year follow-up. There were no significant changes in PA and BMD. When stratified with respect to age, sex, presence of subsequent falls and OP fractures, there were no significant differences in fracture-specific pain/disability, PA, FOF, and BMD at baseline, six months or four years after DRF. The physical HS was significantly (p<0.05) less/poorer among those with secondary falls (lower by 2-6 points) and fractures (lower by 5-6 points) compared to those without. Similarly, mental HS was significantly (p<0.05) poorer among people with secondary falls (lower by 2-6 points) and in 50-64 year age group (lower by 3-5 points) than those without secondary falls and in 65-80 year age group, respectively. CONCLUSION: Post DRF, the majority of the improvement in fracture-specific pain/disability, FOF and HS was completed at six months and very small changes were observed between the six month and four year follow-up. LEVEL OF EVIDENCE: NA. PMID- 28993003 TI - The fasting serum triglyceride levels of elderly population with different progression stages of diabetes mellitus in China. AB - AIMS: This cross-sectional study aimed to investigate triglyceride level among Chinese elderly population with different diabetic progressions and related factors of triglyceride. METHODS: Study participants (>=65years) were recruited from a nationwide cross-sectional surveillance and were divided into four subgroups according to diabetic progression. Their information was obtained via questionnaire and physical examination. Their lipids in fasting serum samples were analyzed. RESULTS: The serum triglyceride levels (mmol/L, mean+/-SD) were 1.3+/-0.8 (subgroup of no prediabetes and no DM), 1.5+/-1.0 (subgroup of prediabetes), 1.6+/-1.1 (subgroup of newly diagnosed DM) and 1.7+/-1.1 (subgroup of previously diagnosed DM), respectively. Only one female participant had a higher triglyceride than upper limit for prevention of acute pancreatitis (11.0mmol/L). However, 23.1% of participants and 34.8% of DM participants had higher triglyceride than upper limit for prevention of cardiovascular diseases (1.7mmol/L). Triglyceride level was positively correlated with diabetic progression (rs=0.17, p<0.01). Age, gender, waist-to-height ratio (rather than BMI), systolic pressure, serum total cholesterol and HDL-C levels were statistically correlated with triglyceride level for total participants (R2=0.39, p<0.01). CONCLUSIONS: Aggravation of serum triglyceride level was related to diabetic progression in Chinese elderly population. Triglyceride control was unsatisfactory in Chinese elderly population, especially in elderly population with DM. PMID- 28993004 TI - Cerebral amyloid angiopathy-related cognitive impairment: The search for a specific neuropsychological pattern. AB - Cerebral amyloid angiopathy is diagnosed in stroke units after lobar intracerebral hemorrhage. CAA can also be diagnosed in memory clinics when patients are referred for cognitive impairment assessment, and may be a reason for admission to emergency or neurology departments because of rapidly progressive cognitive or neurological decline, or a transient focal neurological episode. CAA may even be observed in older community-dwelling individuals. Neuropsychological impairment in CAA has been described over the past 20 years. The symptoms most commonly reported are perceptual speed, episodic memory, semantic memory, attention and executive function, and global cognitive impairments. Psychiatric symptoms, such as personality changes, behavioral disturbances and depression, have been more recently described. CAA is also a risk factor for the development of dementia, and its relationship with Alzheimer's disease has been demonstrated in post-mortem studies. Yet, despite the increase in literature on CAA-related cognitive and psychiatric symptoms, the specific characteristics of symptoms in CAA are difficult to assess because of the substantial prevalence of comorbidities such as small vessel disease due to high blood pressure, Lewy body disease and, of course, AD, all of which act as important confounding factors. Also, within the entity of CAA itself, the additive and perhaps synergistic effects of each lesion on cognition remain to be assessed. In the present paper, the focus is on the latest evidence of neuropsychological impairment observed in CAA patients, and the emergence of a possible specific neuropsychological profile due to CAA is also discussed. PMID- 28993005 TI - Adalimumab for nail psoriasis: Efficacy and safety from the first 26 weeks of a phase 3, randomized, placebo-controlled trial. AB - BACKGROUND: Previous clinical trials have not evaluated improvement in nail psoriasis as a primary end point. OBJECTIVE: This phase 3 trial evaluated the safety and efficacy of adalimumab in patients with moderate-to-severe fingernail psoriasis and moderate-to-severe plaque psoriasis. METHODS: Patients were randomized 1:1 to 40 mg adalimumab every other week or placebo. The primary efficacy end point was at least 75% improvement in total-fingernail modified Nail Psoriasis Severity Index (NAPSI75) response rate at week 26. Ranked secondary end point scores evaluated at week 26 were total-fingernail NAPSI and modified NAPSI, nail pain, Nail Psoriasis Physical Functioning Severity, Brigham Scalp Nail Inverse Palmo-Plantar Psoriasis Index, and Physician's Global Assessment (fingernail psoriasis). RESULTS: Of the 217 randomized patients (108 received placebo and 109 received adalimumab), 188 (86.6%) completed 26 weeks of treatment (period A) or escaped early to the open-label period. The study met the primary end point (response rate of 3.4% with placebo vs 46.6% with adalimumab [P < .001]) and all ranked secondary end points. The serious adverse event rates (placebo vs adalimumab) in period A were 4.6% versus 7.3%; the serious infections rates were 1.9% versus 3.7%. LIMITATIONS: Patients with less than 5% BSA involvement were not eligible for enrollment. CONCLUSIONS: After 26 weeks of adalimumab treatment, significant improvements were seen in the primary and all ranked secondary end points and in signs and symptoms of moderate-to-severe nail psoriasis versus with placebo and no new safety risks were identified. PMID- 28993006 TI - Promoting sunscreen use and sun-protective practices in NCAA athletes: Impact of SUNSPORT educational intervention for student-athletes, athletic trainers, and coaches. AB - BACKGROUND: Student-athletes (SAs) have an increased skin cancer risk on account of significant ultraviolet exposure; however, their sun-protective practices are suboptimal. A novel program, Stanford University Network for Sun Protection, Outreach, Research, and Teamwork (SUNSPORT), was designed to target SAs, coaches, and athletic trainers (ATs). OBJECTIVE: To measure the impact of educational intervention on sun protection beliefs and practices of SAs. METHODS: A survey of sun protection beliefs and practices was administered to National Collegiate Athletic Association athletes before and after intervention. SUNSPORT dermatologists educated SAs, coaches, and ATs regarding skin cancer risk and prevention methods. The main outcome was frequency of sunscreen use by SAs before versus after intervention. RESULTS: A total of 846 National Collegiate Athletic Association athletes were surveyed between September 23, 2012, and September 20, 2015. After intervention, significant increases were observed in sunscreen use 4 or more days per week by SAs (from 26% to 39% [P = .02]), SAs spoken to by their coach about sun safety (from 26% to 57% [P = .0001]), and SA recognition of higher skin cancer risk (from 54% to 67% [P = .04]). LIMITATIONS: Intervention in only 1 West Coast university and no paired data. CONCLUSIONS: Following the SUNSPORT intervention, SAs were significantly more likely to use sunscreen, especially if encouraged by their coach. This study emphasizes that education directed to SAs, ATs, and coaches can improve sun-protective practices in SAs. PMID- 28993007 TI - Poor early response to methotrexate portends inadequate long-term outcomes in patients with moderate-to-severe psoriasis: Evidence from 2 phase 3 clinical trials. AB - BACKGROUND: Most methotrexate-treated psoriasis patients do not achieve a long term PASI75 (75% reduction from baseline Psoriasis Area and Severity Index score) response. Indications of nonresponse can be apparent after only 4 weeks of treatment. OBJECTIVE: To develop a prediction rule to identify patients unlikely to respond adequately to methotrexate. METHODS: Patient-level data from CHAMPION (NCT00235820, N = 110) was used to construct a prediction model for week 16 PASI75 by using patient baseline characteristics and week 4 PASI25. A prediction rule was determined on the basis of the sensitivity and specificity and validated in terms of week 16 PASI75 response in an independent validation sample from trial M10-255 (NCT00679731, N = 163). RESULTS: PASI25 achievement at week 4 (odds ratio = 8.917) was highly predictive of response with methotrexate at week 16. Patients with a predicted response probability <30% were recommended to discontinue methotrexate. The rates of week 16 PASI75 response were 65.8% and 21.1% (P < .001) for patients recommended to continue and discontinue methotrexate, respectively. LIMITATIONS: The CHAMPION trial excluded patients previously treated with biologics, and the M10-255 trial had no restrictions. CONCLUSION: A prediction rule was developed and validated to identify patients unlikely to respond adequately to methotrexate. The rule indicates that 4 weeks of methotrexate might be sufficient to predict long-term response with limited safety risk. PMID- 28993008 TI - PIWI family emerging as a decisive factor of cell fate: An overview. AB - PIWI proteins and piRNAs primarily functions as a safeguard of germline cells by activating epigenetic regulations, silencing transposons and maintaining chromatin structure. Increasing evidences reveal that PIWI proteins and piRNAs have broader functions in many vital biological processes including cell proliferation, differentiation and survival. They have been recognized as a crucial factor in the cellular events due their role in controlling mRNA expression, turnover and translation. PIWIs, with or without its partner non coding RNA (piRNA), govern the expression and activity of many transcription factors and signaling molecules by mastering their expression and/or post translational modifications by directly interacting with them. In this review, we focus on the functional role of PIWI family of proteins and piRNA in physiological and pathological conditions. We compile the current knowledge about the impact of alterations of PIWI and/or piRNA on expression and activities of signaling mediators and transcriptional networks associated with cell differentiation, proliferation and survival. PMID- 28993009 TI - Fenugreek galactomannan and citrus pectin improve several parameters associated with glucose metabolism and modulate gut microbiota in mice. AB - OBJECTIVE: Galactomannans derived from fenugreek confer known health benefits; however, there is little information regarding health benefits of citrus pectin (CP) and its association with gut microbiome metabolites. The aim of this study was to examine links between galactomannan and CP consumption, microbiota development, and glucose metabolism. DESIGN: Male C57 BL/6 J mice ages 7 to 8 wk were fed ad libitum with a normal diet or one supplemented with 15% of either galactomannan or CP. At 3 wk, an oral glucose tolerance test was performed. Animals were sacrificed at 4 wk and relevant organs were harvested. RESULTS: Fiber enrichment led to reductions in weight gain, fasting glucose levels, and total serum cholesterol (P < 0.05). Compared with mice fed the normal diet, microbiota populations were altered in both fiber groups and were found to be richer in Bacteroidetes rather than Firmicutes (P < 0.05). The modification was significantly greater in galactomannan-fed than in CP-fed mice (P < 0.0001). Also, enhanced levels of the short-chain fatty acid (SCFA) propionate were found in the cecal contents of CP-fed animals (P < 0.05). Protein expression levels of monocarboxylate transporter 1, which may promote transport of SCFA, were measured in the large intestines after fiber consumption. Enhanced adenosine monophosphate activated protein kinase (AMPK) activation was observed in livers of galactomannan-fed mice (P < 0.05). CONCLUSION: Consumption of diets containing soluble fibers, as used in this study, resulted in gut microbiota comprising a healthier flora, and led to positive effects on weight, glycemic control, and liver beta oxidation via AMPK. PMID- 28993010 TI - Early and Late Retinal Pigment Epithelium Tears after Anti-Vascular Endothelial Growth Factor Therapy for Neovascular Age-Related Macular Degeneration. AB - PURPOSE: To investigate when retinal pigment epithelium (RPE) tears occur and their associated treatment patterns and long-term visual outcomes in patients with neovascular age-related macular degeneration (nAMD) during anti-vascular endothelial growth factor (VEGF) treatment. DESIGN: Case-control analysis from a prospectively designed observational database. PARTICIPANTS: Treatment-naive eyes enrolled in the Fight Retina Blindness! observational study that commenced anti VEGF treatment for nAMD between January 2006 and January 2017 were identified. Cases were defined as eyes in which an RPE tear developed during treatment. Three control eyes per case were matched for age, baseline visual acuity (VA), lesion size, treatment duration before tearing, and duration of follow-up. METHODS: Cases were classified as having early or late tears using a segmented regression model. Baseline characteristics were compared between the 2 groups. Comparisons of VA and injections received between tear eyes and control eyes were performed at baseline, before and immediately after the tear, and then 12 and 24 months later. Visual acuity also was compared among different visits within each group. MAIN OUTCOME MEASURES: Visual acuity, time to tear, and injections received. RESULTS: Fifty-five cases and 165 matched control eyes were included. The segmented regression estimated a breakpoint for the time to tear at 182 days. We therefore defined eyes as having early tears if they tore before the breakpoint (38/55 eyes [69%]), and as late tears if they tore afterward (17/55 eyes [31%]). Baseline VA was significantly lower in early compared with late tears (53.6 vs. 63.4 letters; P = 0.009). Visual acuity had improved in early tears before the tear (+5.6 letters from baseline; P = 0.01), decreased immediately after the tear (-8.3 letters; P = 0.002), then recovered with no difference compared with control eyes 12 and 24 months later (P > 0.05 for both). Late tear eyes had significantly lower VA than control eyes before tearing (55.5 vs. 66.9 letters; P < 0.001). Visual acuity did not decrease significantly after the tear, but continued to decline compared with control eyes at all end points. Both early and late tear eyes received more injections than control eyes after tearing. CONCLUSIONS: Retinal pigment epithelium tears act differently depending on when they occur. Long-term visual outcomes in eyes affected by RPE tearing may be related more to the patient's response to therapy than to the tear itself. PMID- 28993011 TI - Risk Factors for Developing Choroidal Neovascular Membrane and Visual Loss in Punctate Inner Choroidopathy. AB - PURPOSE: To examine a large cohort of subjects with punctate inner choroidopathy (PIC) looking at risk factors for development of choroidal neovascular membrane (CNVM) and visual loss. DESIGN: Retrospective case series. PARTICIPANTS: A total of 203 participants (318 eyes) with PIC seen at Moorfields Eye Hospital between 1996 and 2016. METHODS: Information was gathered from the clinical notes of all subjects identified with PIC. MAIN OUTCOME MEASURES: Development of CNVM, moderate visual loss (MVL) (<=20/50), and severe visual loss (SVL) (<=20/200). RESULTS: Participants were predominantly young (median age at presentation, 32.9 years; interquartile range [IQR], 26.1-42.2), myopic (91.5%), female (87.2%), and white (75.9%). Disease was bilateral at presentation in 115 participants (56.7%), and CNVM was present at presentation in 152 eyes (47.8%). Median follow-up was 8.4 years. New CNVM occurred in 58 eyes (33.5% of affected eyes and 4.3% of initially unaffected eyes). An increased risk of developing CNVM was associated with the presence of a CNVM in the fellow eye (P < 0.0005; hazard ratio [HR], 2.73), and previous oral corticosteroid treatment was associated with halving of the risk of developing CNVM (P = 0.035; HR, 0.45). No difference was observed in visual outcome with oral corticosteroids, but subjects treated with anti-VEGF had better visual outcomes (12-month median visual acuity, logarithm of the minimum angle of resolution [logMAR] 0.00 with anti-VEGF and 0.20 without; P = 0.018). Median best-corrected visual acuity (BCVA) was 20/30 at presentation (IQR, 0.00 0.50) and remained at 20/30 throughout all follow-up periods. Moderate visual loss occurred in 40 eyes (12.6%), with an incidence of 0.01 per eye-year, and SVL occurred in 49 eyes (15.4%), with an incidence of 0.01 per eye-year. Female participants were half as likely as male participants to develop MVL (P = 0.030; HR, 0.448), and participants with CNVM had a higher risk of MVL (P = 0.003; HR, 21.074). CONCLUSIONS: Visual loss is common in subjects with PIC, predominantly secondary to late development of CNVM. Treatment with oral corticosteroids may help to reduce the risk of CNVM development, and anti-VEGF therapy for CNVM was associated with better clinical outcomes. PMID- 28993012 TI - Can Microalgae Remove Pharmaceutical Contaminants from Water? AB - The increase in worldwide water contamination with numerous pharmaceutical contaminants (PCs) has become an emerging environmental concern due to their considerable ecotoxicities and associated health issues. Microalgae-mediated bioremediation of PCs has recently gained scientific attention, as microalgal bioremediation is a solar-power driven, ecologically comprehensive, and sustainable reclamation strategy. In this review, we comprehensively describe the current research on the possible roles and applications of microalgae for removing PCs from aqueous media. We summarize several novel approaches including constructing microbial consortia, acclimation, and cometabolism for enhanced removal of PCs by microalgae, which would improve practical feasibility of these technologies. Some novel concepts for degrading PCs using integrated processes and genetic modifications to realize algal-based bioremediation technologies are also recommended. PMID- 28993013 TI - Right cerebral hemisphere specialization for quiet and perturbed body balance control: Evidence from unilateral stroke. AB - Our aim in this investigation was to assess the relative importance of each cerebral hemisphere in quiet and perturbed balance, based on uni-hemispheric lesions by stroke. We tested the hypothesis of right cerebral hemisphere specialization for balance control. Groups of damage either to the right (RHD, n=9) or the left (LHD, n=7) cerebral hemisphere were compared across tasks requiring quiet balance or body balance recovery following a mechanical perturbation, comparing them to age-matched nondisabled individuals (controls, n=24). They were evaluated in conditions of full and occluded vision. In Experiment 1, the groups were compared in the task of quiet standing on (A) rigid and (B) malleable surfaces, having as outcome measures center of pressure (CoP) amplitude and velocity sway. In Experiment 2, we evaluated the recovery of body balance following a perturbation inducing forward body oscillation, having as outcome measures CoP displacement, peak hip and ankle rotations and muscular activation of both legs. Results from Experiment 1 showed higher values of CoP sway velocity for RHD in comparison to LHD and controls in the anteroposterior (rigid surface) and mediolateral (malleable surface) directions, while LHD had lower balance stability than the controls only in the mediolateral direction when supported on the rigid surface. In Experiment 2 results showed that RHD led to increased values in comparison to LHD and controls for anteroposterior CoP displacement and velocity, time to CoP direction reversion, hip rotation, and magnitude of muscular activation in the paretic leg, while LHD was found to differ in comparison to controls in magnitude of muscular activation of the paretic leg and amplitude of mediolateral sway only. These results suggest that damage to the right as compared to the left cerebral hemisphere by stroke leads to poorer postural responses both in quiet and perturbed balance. That effect was not altered by manipulation of sensory information. Our findings suggest that the right cerebral hemisphere plays a more prominent role in efferent processes responsible for balance control. PMID- 28993015 TI - [An unusual presentation of mantle cell lymphoma]. PMID- 28993014 TI - (R)-alpha-Lipoyl-Gly-l-Pro-l-Glu dimethyl ester as dual acting agent for the treatment of Alzheimer's disease. AB - In this study, effects of LA-GPE (R-alpha-Lipoyl-Gly-l-Pro-l-Glu dimethyl ester) and GPE (Gly-L-Pro-L-Glu) on the cytotoxic action of Abeta1-42 were tested with differentiated human neuroblastoma SH-SY5Y cells as cellular Alzheimer model via measurements of mitochondrial viability (MTT assay) and lactate dehydrogenase release (LDH assay). Effects of LA-GPE and GPE on acetylcholinesterase (AChE) activity, total antioxidant capacity (TAC) and total oxidative status (TOS) levels, and neural cell apoptosis and necrosis were also determined. In addition, biological safety of these novel formulations was evaluated in human blood cells using different cytotoxicity and genotoxicity assays. Our results indicated that both compounds could block Abeta1-42 induced cell death. LA-GPE reduced Abeta induced AChE activity and oxidative stress, suggesting it as a multifunctional compound potentially valuable for the treatment of Alzheimer's disease (AD). PMID- 28993016 TI - [Cosmetics and topical medications in acne: Where is the boundary?] AB - Acne is a chronic disease that may cause sequels such as atrophic or hypertrophic scars or post-inflammatory hyperpigmentation. Topical and systemic medications with proven pharmacologic activity and which have received marketing authorization are the key actors in the treatment of acne. However, these topical or systemic treatments frequently cause adverse effects related to impairment of the skin barrier, and cosmetics must therefore be used in combination to help protect the skin barrier. Nowadays, new cosmetic products containing active ingredients tested in vitro or in a small number of subjects have changed the world of cosmetics. In being described as "dermo-cosmetic" and in integrating active ingredients in their formulations, these cosmetics are now being presented as being specifically adapted for a given disease, and no longer limited to skin care and hygiene but suitable as an adjunctive or even an alternative to current medications. The aim of this article is to provide a better understanding of the respective roles of medications and cosmetics in the management of acne. PMID- 28993017 TI - Environmental non-governmental organizations and urban environmental governance: Evidence from China. AB - Environmental non-governmental organizations (ENGOs) play an increasingly important role in the process of urban environmental governance, especially in some developing countries such as China. However, existing studies pay little attention to such an issue in China. In this paper, we consider 113 cities in China from the pollution information transparency index (PITI) list released by ENGOs as the treatment group and some other cities as the control group, and use the difference-in-differences (DID) model and propensity score matching DID (PSM DID) model to explore the role of ENGOs in China's urban environmental governance. The results show that ENGOs play a significantly positive and robust role in China's urban environmental governance. Furthermore, using regression analysis for eastern, central, and western China, we find that the influence of ENGOs exists in eastern and central China rather than in western China. In addition, the results of the Placebo test indicate that the effect of ENGOs shows an upward trend since 2008. We suggest that ENGOs' role should be strengthened in China, and governments at various levels should take into account environmental information released by ENGOs and consider appropriate measures to improve local environment quality using the obtained information. PMID- 28993018 TI - Functional correlates of the position of the axis of rotation of the mandible during chewing in non-human primates. AB - The location of the axis of rotation (AoR) of the mandible was quantified using the helical axis (HA) in eight individuals from three species of non-human primates: Papio anubis, Cebus apella, and Macaca mulatta. These data were used to test three hypotheses regarding the functional significance of anteroposterior condylar translation - an AoR located inferior to the temporomandibular joint (TMJ) - during chewing: minimizing impingement of the gonial region on cervical soft tissue structures during jaw opening; avoiding stretching of the inferior alveolar neurovascular bundle (IANB); and increasing jaw-elevator muscle torques. The results reveal that the HA is located near the occlusal plane in Papio and Cebus, but closer to the condyle in Macaca; is located anteroinferior to the TMJ during both opening and closing in Papio, as well as during opening in Macaca and Cebus; and varies in its location during closing in Macaca and Cebus. The impingement hypothesis is not supported by interspecific variation in HA location: species with larger gonial angles like Cebus do not have more inferiorly located HAs than species with more obtuse mandibular angles like Papio. However, intraspecific variation provides some support for the impingement hypothesis. The HA seldom passes near or through the lingula, falsifying the hypothesis that its location is determined by the sphenomandibular ligament, and the magnitudes of strain associated with a HA at the TMJ would not be large enough to cause problematic stretching of the IANB. HA location does affect muscle moment arms about the TMJ, with implications for the torque generation capability of the jaw-elevator muscles. In Cebus, a HA farther away from the TMJ is associated with larger jaw-elevator muscle moment arms about the joint than if it were at the TMJ. The effects of HA location on muscle strain and muscle moment arms are largest at large gapes and smallest at low gapes, suggesting that if HA location is of functional significance for primate feeding system performance, it is more likely to be in relation to large gape feeding behaviors than chewing. Its presence in humans is most parsimoniously interpreted as a primitive retention from non-human primate ancestors and explanations for the presence of anteroposterior condylar translation in humans need not invoke either the uniqueness of human speech or upright posture. PMID- 28993020 TI - Corrigendum to "Crystal structure of human transglutaminase 2 in complex with adenosine triphosphate" [Int. J. Biol. Macromol. 47 (2010) 190-195]. PMID- 28993019 TI - A modified formula for dose calculations of stereotactic ablative body radiotherapy for non-small cell lung cancer. AB - To provide a modified formula consistent with the Monte Carlo (MC) algorithm for dose calculations during stereotactic ablative body radiotherapy for non-small cell lung cancer. Seventy CyberKnife treatment plans were calculated and analyzed by MC and ray-tracing (RT) algorithms, separately. Parameters of treatment plans were compared, and those associated with differences of dose distributions were analyzed to establish a modified formula. Gross tumor volume and tumor tracking volume (TTV) were defined as the evident disease on the sequences of the window width and level of the lung and the mediastinum. Additionally, the formula was validated by another 20 plans. The prescription dose of the 90 patients was 60 Gy/5f. The RT algorithm overestimated the planning target volume (PTV) D95 by an average of 8.59 Gy and the gross tumor volume D99 by an average of 5.84 Gy. The homogeneity index of PTV was underestimated by 0.11 on average, whereas the conformity index and new conformity index was underestimated by 0.05. The RT algorithm overestimated the dose distribution to the spinal cord by 2.23 Gy, the esophagus by 1.96 Gy, the trachea by 1.89 Gy, the left-sided bronchus by 1.77 Gy, the right-sided bronchus by 1.64 Gy, and the heart by 2.16 Gy. The average whole lung dose volumes of lung tissues and dose volumes of V5 were overestimated by 2.69 Gy and 7.52%, respectively. A power function distribution (R2 = 0.8626) was confirmed between PTV D95 and TTV volumes. PTV D95 calculated by the MC algorithm could be computed easily with TTV and PTV D95 calculated by the RT algorithm based on the formula. The modified equation was more consistent with MC algorithm than with other formula, which could be a reference to those not accessible to the MC algorithm. PMID- 28993021 TI - Regulation of zebrafish (Danio rerio) locomotor behavior and circadian rhythm network by environmental steroid hormones. AB - Environmental exposure of fish to steroid hormones through wastewater and agricultural runoff may pose a health risk. Thus far, ecotoxicological studies have largely been focused on the disruption of the sex hormone system, but additional effects have been poorly investigated. Here we report on the effects of a series of different natural and synthetic steroid hormones on the locomotor behavior and the transcriptional levels of core clock genes in zebrafish eleuthero-embryos (Danio rerio). Of the 20 steroids analyzed, progestins and corticosteroids, including progesterone and cortisol, significantly decreased the locomotor activities of eleuthero-embryos at concentrations as low as 16 ng/L, while estrogens such as 17beta-estradiol led to an increase. Consistently, progestins and corticosteroids displayed similar transcriptional effects on core clock genes, which were remarkably different from those of estrogens. Of these genes, per1a and nr1d2a displayed the most pronounced alterations. They were induced upon exposure to various progestins and corticosteroids and could be recovered using the progesterone receptor/glucocorticoid receptor antagonist mifepristone; this, however, was not the case for estrogens and the estrogen receptor antagonist 4-hydroxy-tamoxifen. Our results suggest that steroid hormones can modulate the circadian molecular network in zebrafish and provide novel insights into their mode of actions and potential environmental risks. PMID- 28993022 TI - Atmospheric nitrogen deposition in the Yangtze River basin: Spatial pattern and source attribution. AB - The Yangtze River basin is one of the world's hotspots for nitrogen (N) deposition and likely plays an important role in China's riverine N output. Here we constructed a basin-scale total dissolved inorganic N (DIN) deposition (bulk plus dry) pattern based on published data at 100 observational sites between 2000 and 2014, and assessed the relative contributions of different reactive N (Nr) emission sectors to total DIN deposition using the GEOS-Chem model. Our results show a significant spatial variation in total DIN deposition across the Yangtze River basin (33.2 kg N ha-1 yr-1 on average), with the highest fluxes occurring mainly in the central basin (e.g., Sichuan, Hubei and Hunan provinces, and Chongqing municipality). This indicates that controlling N deposition should build on mitigation strategies according to local conditions, namely, implementation of stricter control of Nr emissions in N deposition hotspots but moderate control in the areas with low N deposition levels. Total DIN deposition in approximately 82% of the basin area exceeded the critical load of N deposition for semi-natural ecosystems along the basin. On the basin scale, the dominant source of DIN deposition is fertilizer use (40%) relative to livestock (11%), industry (13%), power plant (9%), transportation (9%), and others (18%, which is the sum of contributions from human waste, residential activities, soil, lighting and biomass burning), suggesting that reducing NH3 emissions from improper fertilizer (including chemical and organic fertilizer) application should be a priority in curbing N deposition. This, together with distinct spatial variations in emission sector contributions to total DIN deposition also suggest that, in addition to fertilizer, major emission sectors in different regions of the basin should be considered when developing synergistic control measures. PMID- 28993023 TI - Spatial distribution and exposure risks of ambient chlorinated polycyclic aromatic hydrocarbons in Tokyo Bay area and network approach to source impacts. AB - Chlorinated polycyclic aromatic hydrocarbons (ClPAHs) receive increasing attention as hazardous pollutants in terms of the high environmental persistence and toxicities. Ambient concentrations of 24 ClPAHs and 24 PAHs were investigated at 14 sites in the Tokyo Bay area of Japan. Twelve of 18 ClPAH species were detected in air samples, in spite of small sampling volumes. Mean concentrations of total PAHs in gas and particle phases were 5400 and 1400 pg/m3, and mean concentrations of total ClPAHs in gas and particle phases were 40 and 14 pg/m3, respectively. The spatial distributions of both total ClPAH and PAH concentrations indicated heavy pollution at sites in industrial activity areas. Principal component analysis suggested that the dominant sources of gaseous and particulate ClPAHs differed substantially from each other. In particular, gaseous ClPAHs could be produced by specific sources different from those of particulate ClPAHs. However, the dominant sources of particulate ClPAHs could be the same as those of particulate PAHs, including industrial activities such as steel and gas production plants and natural gas-fired power plants. The influences of spatial relationships among sampling sites were represented using a network analysis. The constructed network showed that ambient ClPAHs and PAHs were dominated by local rather than regional pollution, because there were weaker relationships among nearby sites. Finally, exposure risks for ClPAHs were dominated by 7 chlorobenz[a]anthracene, followed by 9-chlorophenanthrene and 6 chlorobenzo[a]pyrene, and total risk was ~1/200 that of PAHs. PMID- 28993024 TI - Exposure to cocaine and its main metabolites altered the protein profile of zebrafish embryos. AB - Illicit drugs have been identified as emerging aquatic pollutants because of their widespread presence in freshwaters and potential toxicity towards aquatic organisms. Among illicit drug residues, cocaine (COC) and its main metabolites, namely benzoylecgonine (BE) and ecgonine methyl ester (EME), are commonly detected in freshwaters worldwide at concentration that can induce diverse adverse effects to non-target organisms. However, the information of toxicity and mechanisms of action (MoA) of these drugs, mainly of COC metabolites, to aquatic species is still fragmentary and inadequate. Thus, this study was aimed at investigating the toxicity of two concentrations (0.3 and 1.0 MUg/L) of COC, BE and EME similar to those found in aquatic ecosystems on zebrafish (Danio rerio) embryos at 96 h post fertilization through a functional proteomics approach. Exposure to COC and both its metabolites significantly altered the protein profile of zebrafish embryos, modulating the expression of diverse proteins belonging to different functional classes, including cytoskeleton, eye constituents, lipid transport, lipid and energy metabolism, and stress response. Expression of vitellogenins and crystallins was modulated by COC and both its main metabolites, while only BE and EME altered proteins related to lipid and energy metabolism, as well as to oxidative stress response. Our data confirmed the potential toxicity of low concentrations of COC, BE and EME, and helped to shed light on their MoA on an aquatic vertebrate during early developmental period. PMID- 28993025 TI - Distribution and predictors of urinary polycyclic aromatic hydrocarbon metabolites in two pregnancy cohort studies. AB - Pregnant women and their fetuses represent susceptible populations to environmental contaminants. Exposure to polycyclic aromatic hydrocarbons (PAHs) among pregnant women may contribute to adverse birth outcomes such as preterm birth. Multiple previous studies have assessed airborne sources of PAHs among pregnant women but few have measured urinary PAH metabolites which can capture total exposure through multiple routes. The aim of this study was to bridge this knowledge gap by assessing longitudinal urinary PAH metabolite concentrations over two time points in pregnancy cohorts in Boston (N = 200) and Puerto Rico (N = 50) to better understand exposure distributions throughout pregnancy and how they relate to demographic factors. Urine samples were analyzed for 1-NAP, 2-NAP, 2-FLU, 1-PHE, 2,3-PHE, 4-PHE, 9-PHE, and 1-PYR. Concentrations of 2-NAP, 1-PYR, and 4-PHE were higher in Puerto Rico, while all other metabolites were present in higher concentrations in Boston. In Puerto Rico, intraclass correlation coefficients (ICC) were weak to moderate, ranging from 0.06 to 0.42. PAH metabolite concentrations were significantly higher among younger, heavier (except 1-NAP and 9-PHE), and less educated individuals in Boston only. Consistent significant associations between PAH concentrations and measured covariates were not found in Puerto Rico. Our results suggest that potentially important differences in PAH exposure exist between these two populations. Additionally, our results indicate that multiple urinary measurements are required to accurately assess PAH exposure throughout pregnancy. PMID- 28993026 TI - Effects of physical characteristics of carbon black on metabolic regulation in mice. AB - Potential adverse effects of human exposure to carbon black (CB) have been reported, but limited knowledge regarding CB-regulated metabolism is currently available. To evaluate how physical parameters of CB influence metabolism, we investigated CB and diesel exhaust particles (DEPs) and attempted to relate various physical parameters, including the hydrodynamic diameter, zeta potential, and particle number concentrations, to lung energy metabolism in female BALB/c mice. A body weight increase was arrested by 3 months of exposure to CB of smaller-size fractions, which was negatively correlated with pyruvate in plasma. There were no significant differences in cytotoxic lactate dehydrogenase (LDH) or total protein in bronchoalveolar lavage fluid (BALF) after 3 months of CB exposure. However, we observed alterations in acetyl CoA and the NADP/NADPH ratio in lung tissues with CB exposure. Additionally, the NADP/NADPH ratio was associated with the zeta potential of CB. Mild peribronchiovascular and interstitial inflammation and multinucleated giant cells (macrophages) with a transparent and rhomboid appearance and containing foreign bodies were observed in lung sections. We suggest that physical characteristics of CB, such as the zeta potential, may disrupt metabolism after pulmonary exposure. These results, therefore, provide the first evidence of a link between pulmonary exposure to CB and metabolism. PMID- 28993027 TI - Methylmercury photodemethylation is inhibited in lakes with high dissolved organic matter. AB - Photodemethylation can be one of the primary processes for loss of neurotoxic methylmercury (MeHg) in freshwater lakes. Few studies have quantified seasonal variations in photodemethylation rate constants as a function of dissolved organic matter (DOM). We conducted 1-week irradiation experiments in two seasons to test for spatial and temporal differences in photodemethylation potential in temperate lake waters. Six study lakes in Kejimkujik National Park, Nova Scotia were sampled in summer and fall to include a range of naturally occurring DOM concentrations (4.4-13.4 and 3.9-16.4 mg C L-1, respectively). A negative linear relationship (R2 = 0.76, p = 0.01) was found between DOM concentration and photodemethylation rate constant across seasons, indicating that DOM is a strong predictor of MeHg photodemethylation independent of seasonal effects. The two highest carbon lakes (BDW and PEB) had significantly higher energy-normalized photodemethylation rate constants in summer compared to fall corresponding with lower DOM concentrations in summer relative to fall. Additionally, there were negative linear relationships between MeHg photodemethylation and DOM photomineralization (R2s = 0.58-0.72) and DOM photobleaching (R2s = 0.83-0.90). This key finding suggests that competition for photons within DOM structures may reduce the potential for MeHg photodemethylation in high carbon waters and that this relationship persists across seasons. PMID- 28993028 TI - The case for DNA methylation based molecular profiling to improve diagnostic accuracy for central nervous system embryonal tumors (not otherwise specified) in adults. AB - Central nervous system primitive neuro-ectodermal tumors (CNS-PNETs), have recently been re-classified in the most recent 2016 WHO Classification into a standby catch all category, "CNS Embryonal Tumor, not otherwise specified" (CNS embryonal tumor, NOS) based on epigenetic, biologic and histopathologic criteria. CNS embryonal tumors (NOS) are a rare, histologically and molecularly heterogeneous group of tumors that predominantly affect children, and occasionally adults. Diagnosis of this entity continues to be challenging and the ramifications of misdiagnosis of this aggressive class of brain tumors are significant. We report the case of a 45-year-old woman who was diagnosed with a central nervous system embryonal tumor (NOS) based on immunohistochemical analysis of the patient's tumor at diagnosis. However, later genome-wide methylation profiling of the diagnostic tumor undertaken to guide treatment, revealed characteristics most consistent with IDH-mutant astrocytoma. DNA sequencing and immunohistochemistry confirmed the presence of IDH1 and ATRX mutations resulting in a revised diagnosis of high-grade small cell astrocytoma, and the implementation of a less aggressive treatment regime tailored more appropriately to the patient's tumor type. This case highlights the inadequacy of histology alone for the diagnosis of brain tumours and the utility of methylation profiling and integrated genomic analysis for the diagnostic verification of adults with suspected CNS embryonal tumor (NOS), and is consistent with the increasing realization in the field that a combined diagnostic approach based on clinical, histopathological and molecular data is required to more accurately distinguish brain tumor subtypes and inform more effective therapy. PMID- 28993029 TI - Water depollution using metal-organic frameworks-catalyzed advanced oxidation processes: A review. AB - This paper presents a review on the environmental applications of metal-organic frameworks (MOFs), which are inorganic-organic hybrid highly porous crystalline materials, prepared from metal ion/clusters and multidentate organic ligands. The emphases are made on the enhancement of the performance of advanced oxidation processes (AOPs) (photocatalysis, Fenton reaction methods, and sulfate radical (SO4-)-mediated oxidations) using MOFs materials. MOFs act as adsorption and light absorbers, leading to superior performance of photocatalytic processes. More recent examples of photocatalytic degradation of dyes are presented. Additionally, it is commonly shown that Fe-based MOFs exhibited excellent catalytic performance on the Fenton-based and SO4*--mediated oxidations of organic pollutants (e.g., dyes, phenol and pharmaceuticals). The significantly enhanced generation of reactive species such as OH and/or SO4- by both homogeneous and heterogeneous catalysis was proposed as the possible mechanism for water depollution. Based on the existing literature, the challenge and future perspectives in MOF-based AOPs are addressed. PMID- 28993030 TI - A Maternal Functional Module in the Mammalian Oocyte-To-Embryo Transition. AB - Prior to zygotic genome activation, early mammalian development relies on maternal-effect genes to orchestrate the oocyte-to-embryo transition. Recently, a subcortical maternal complex (SCMC) was identified to be essential for mouse preimplantation development. The SCMC integrates multiple proteins encoded by maternal-effect genes and appears to be functionally conserved across mammalian species. In addition, mutations in human SCMC genes are associated with certain human reproductive disorders. Here, we highlight recent advances in the biology of the SCMC and propose that this complex may be a representative example of maternal functional modules in mammalian oocyte-to-embryo transition. These findings may provide further insights into the molecular regulation of mammalian early embryogenesis, with possible implications for human early embryonic development and reproduction medicine. PMID- 28993031 TI - Targeting ATP-Citrate Lyase in Hyperlipidemia and Metabolic Disorders. AB - Chronic overnutrition and a sedentary lifestyle promote imbalances in metabolism, often manifesting as risk factors for life-threating diseases such as atherosclerotic cardiovascular disease (ASCVD) and nonalcoholic fatty liver disease (NAFLD). Nucleocytosolic acetyl-coenzyme A (CoA) has emerged as a central signaling node used to coordinate metabolic adaptations in response to a changing nutritional status. ATP-citrate lyase (ACL) is the enzyme primarily responsible for the production of extramitochondrial acetyl-CoA and is thus strategically positioned at the intersection of nutrient catabolism and lipid biosynthesis. Here, we discuss recent findings from preclinical studies, as well as Mendelian and clinical randomized trials, demonstrating the importance of ACL activity in metabolism, and supporting its inhibition as a potential therapeutic approach to treating ASCVD, NAFLD, and other metabolic disorders. PMID- 28993032 TI - [Hydropneumothorax revealing Mycobacterium intracellulare pleural infection]. PMID- 28993033 TI - CA 19-9 to peritoneal carcinomatosis index (PCI) ratio is prognostic in patients with epithelial appendiceal mucinous neoplasms and peritoneal dissemination undergoing cytoreduction surgery and intraperitoneal chemotherapy: A retrospective cohort study. AB - BACKGROUND: Serum tumour levels have been shown to be prognostic in patients with epithelial appendiceal mucinous neoplasms with peritoneal dissemination (pseudomyxoma peritonei (PMP)). A singular index which incorporates both tumour activity (as depicted by serum tumour marker levels) and tumour volume (as depicted by peritoneal carcinomatosis index (PCI)), may give a more precise surrogate of tumour biological behaviour. The prognostic implication of this index has not yet been reported. METHODS: A retrospective cohort study of all patients with PMP managed from 1996 to 2016 with cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) was performed by analysing the survival effect of the ratio of preoperative serum CEA, CA19.9 and CA125 to PCI. RESULTS: Three hundred and eighty-six patients were included. In patients with low-grade PMP, elevated CA19-9/PCI ratio resulted in poorer median overall survival times (104 months vs NR, 95%CI 83 - NR, log-rank p < 0.001) and was an independent predictor of reduced overall survival on multivariable analysis (adjusted HR 5.60, 95%CI 1.60-19.68, p = 0.007). In patients with high-grade PMP, no statistically significant difference in survival was recognised. CONCLUSION: CA19-9/PCI ratio is an independent prognostic factor for overall survival in patients with low grade PMP undergoing CRS and IPC. By accounting for both tumour activity and tumour volume simultaneously, this novel index behaves as a surrogate of tumour biology and provides a useful adjunct for decisions regarding treatment allocation in this patient group. PMID- 28993034 TI - [Massive left atrial calcification]. PMID- 28993035 TI - Outcomes of hybrid procedure for type B aortic dissection with an aberrant right subclavian artery. AB - OBJECTIVE: To report our single-center experience of the hybrid procedure for type B aortic dissection (TBAD) with an aberrant right subclavian artery (ARSA) and the early to midterm outcomes in these patients. METHODS: From December 2011 to February 2016, 16 patients (12 males; median age, 51 years; range, 40-66 years) underwent thoracic endovascular aortic repair and extraanatomic bypass hybrid procedure for TBAD with an ARSA in our center. Demographics, coexisting medical conditions, imaging features, operation details, and follow-up outcomes of these patients were collected retrospectively and analyzed. RESULTS: Duration from onset to hybrid procedure ranged from 5 to 57 days, with a median duration of 17 days. The median duration of stay in the intensive care unit and duration of in-hospital stay was 126 hours (range, 14-450 hours) and 21 days (range, 11-31 days), respectively. The overall technique success rate was 100%. No perioperative death, major stroke, or spinal cord ischemia was registered. Immediate type Ia endoleak was detected in three patients (18.8%) and immediate type II endoleak was detected in one patient (6.3%). One access-related complication occurred, which was a femoral artery pseudoaneurysm requiring compression bandage. Brachial plexus injury was observed in two patients (12.5%) with weakness of the upper extremity. The median follow-up was 33 months (range, 11-59 months). During follow-up, a retrograde type A aortic dissection was found in one patient (6.3%) 3 months after procedure. The occlusion of left common carotid artery to left subclavian artery bypasses were confirmed by computed tomography angiography in two patients (12.5%). They were left untreated for no symptoms. Reintervention was required in one patient (6.3%) for persistent type II endoleak by using Amplatzer plugs to seal the origin of the ARSA 20 months after the operation. There was no recorded death or stroke during the study period. CONCLUSIONS: Our limited experience demonstrates that a hybrid procedure is a viable and relatively safe treatment strategy for patients with TBAD and an ARSA. A larger series of cases with a longer follow-up is needed to substantiate these results. PMID- 28993036 TI - The Association of Emergency Department Treatments for Hyperglycemia with Glucose Reduction and Emergency Department Length of Stay. AB - BACKGROUND: Hyperglycemia is frequently encountered in the emergency department (ED), and insulin and intravenous fluid are commonly administered to reduce glucose prior to discharge. OBJECTIVES: We sought to determine the magnitude of the association between glucose-lowering therapies and 1) actual glucose reduction and 2) ED length of stay (LOS). METHODS: We performed a retrospective chart review study of patients with any glucose level >= 400 mg/dL who were discharged from the ED between January 2010 and December 2011. Generalized estimating equation models were created for the ED outcomes of glucose reduction and ED LOS with primary predictors of insulin and intravenous fluids administered. RESULTS: The cohort consisted of 422 patients with 566 encounters. Median arrival and discharge glucose were 473 mg/dL and 326 mg/dL, respectively, with median glucose reduction of 144 mg/dL. Median length of stay was 253 min. After adjustment, 10 units of subcutaneous insulin and 1 liter of intravenous fluid were associated with 33 mg/dL and 27 mg/dL glucose reduction, respectively. Every liter of intravenous fluid administered was associated with a 45-min increase in ED LOS; insulin administration was not associated with ED LOS. CONCLUSION: In patients with type 2 diabetes who present with moderate to severe hyperglycemia, both insulin and intravenous fluids are associated with a modest glucose reduction. Intravenous fluids were associated with a significant increase in ED LOS, but insulin was not. These results should be considered when determining whether to administer therapies that reduce glucose in the ED. PMID- 28993037 TI - Reversible Stress Cardiomyopathy Secondary to Aneurysmal Subarachnoid Hemorrhage: A Case Report. AB - BACKGROUND: Acute cerebral incidents have been correlated with cardiac manifestations. Specifically, subarachnoid hemorrhage has been correlated with a syndrome described as neurogenic stress cardiomyopathy and mimics acute coronary syndrome. CASE REPORT: A 55-year-old woman presented at the Emergency Department of our hospital complaining of vomiting and headache of sudden onset. Computed tomography angiography revealed a ruptured aneurysm at the tip of the basilar artery and the patient underwent a successful complete embolism of the sac of the aneurysm. During hospitalization, the patient developed electrocardiographic alterations and elevation of cardiac biomarkers, and echocardiography showed an impairment of left ventricular systolic function. The patient was diagnosed with neurogenic stress cardiomyopathy and she was treated conservatively. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Clinicians should be aware of neurogenic stress cardiomyopathy because early diagnosis and treatment are the cornerstones for achieving a better outcome. PMID- 28993039 TI - Aortic Intramural Hematoma, Stanford Type A. PMID- 28993038 TI - Capnography in the Emergency Department: A Review of Uses, Waveforms, and Limitations. AB - BACKGROUND: Capnography has many uses in the emergency department (ED) and critical care setting, most commonly cardiac arrest and procedural sedation. OBJECTIVE OF THE REVIEW: This review evaluates several indications concerning capnography beyond cardiac arrest and procedural sedation in the ED, as well as limitations and specific waveforms. DISCUSSION: Capnography includes the noninvasive measurement of CO2, providing information on ventilation, perfusion, and metabolism in intubated and spontaneously breathing patients. Since the 1990s, capnography has been utilized extensively for cardiac arrest and procedural sedation. Qualitative capnography includes a colorimetric device, changing color on the amount of CO2 present. Quantitative capnography provides a numeric value (end-tidal CO2), and capnography most commonly includes a waveform as a function of time. Conditions in which capnography is informative include cardiac arrest, procedural sedation, mechanically ventilated patients, and patients with metabolic acidemia. Patients with seizure, trauma, and respiratory conditions, such as pulmonary embolism and obstructive airway disease, can benefit from capnography, but further study is needed. Limitations include use of capnography in conditions with mixed pathophysiology, patients with low tidal volumes, and equipment malfunction. Capnography should be used in conjunction with clinical assessment. CONCLUSIONS: Capnography demonstrates benefit in cardiac arrest, procedural sedation, mechanically ventilated patients, and patients with metabolic acidemia. Further study is required in patients with seizure, trauma, and respiratory conditions. It should only be used in conjunction with other patient factors and clinical assessment. PMID- 28993040 TI - Severe Pulmonary Cement Embolism. PMID- 28993041 TI - Diarrhoea during checkpoint blockade, not always colitis. PMID- 28993043 TI - Corrigendum to "Lack of glutathione peroxidase-1 facilitates a pro-inflammatory and activated vascular endothelium" [Vasc. Pharmacol. 79 (2016) 32-42]. PMID- 28993042 TI - Effect of sacroiliac manipulation on postural sway in quiet standing: a randomized controlled trial. AB - BACKGROUND: Sacroiliac joint manipulation can alter joint and muscle control mechanisms through local and remote effects. Postural balance is controlled by supraspinal (rambling) and spinal-peripheral (trembling) mechanisms. A manipulation may interfere with postural control in quiet standing. OBJECTIVES: To evaluate the immediate effects of sacroiliac joint manipulation on postural control in patients with (1) sacroiliac dysfunction and (2) to determine whether rambling and trembling are affected by sacroiliac joint manipulation. METHODS: 32 patients aged between 20 and 50 years old were selected by convenience after confirmation of sacroiliac joint dysfunction by clinical examination. These patients were randomly allocated either to manipulation or sham manipulation group. Displacement, velocity and frequency of the center of pressure, rambling and trembling in the anterior-posterior and medial-lateral directions were our primary outcomes and analyzed immediately before and after the intervention in quiet standing. The physical therapists who performed the physical, biomechanical and statistical examinations, were all blinded to the patients' grouping. RESULTS: No differences were found between the two groups but trembling velocity (0.14 and -0.11 for intervention and sham group, respectively) and frequency (0.17 and 0.11 for intervention and sham group respectively) increased after intervention in the treatment group in the anterior-posterior direction. CONCLUSION: Generally, sacroiliac joint manipulation had no superiority than sham treatment regarding postural control as measured by rambling-trembling analysis of center of pressure. Manipulation may increase muscle activation in the treatment group due to increased trembling parameters. Trial number: IRCT2014072715932N8 - http://www.irct.ir/searchresult.php?keyword=%D8%B3%D9%88%DB%8C%D9%87&id=15932&fie d=&number=8&prt=13&total=10&m=1. PMID- 28993044 TI - Risk factors for early readmission after total pancreatectomy and islet auto transplantation. AB - BACKGROUND: Little published data exist examining causes of hospital readmission following total pancreatectomy with islet autotransplantation (TPIAT). METHODS: A retrospective analysis was performed of a prospectively collected institutional TPIAT database. Primary outcome was unplanned readmission to the hospital within 30 days from discharge. Reasons and risk factors for readmission as well as islet function were evaluated and compared by univariate and multivariate analysis. RESULTS: 83 patients underwent TPIAT from 2006 to 2014. 21 patients (25.3%) were readmitted within 30 days. Gastrointestinal problems (52.4%) and surgical site infection (42.8%) were the most common reasons for readmission. Initial LOS and reoperation were risk factors for early readmission. Patients with delayed gastric emptying (DGE) were three times more likely to get readmitted. In multivariate analysis, patients undergoing pylorus preservation surgery were nine times more likely to be readmitted than the antrectomy group. CONCLUSION: Early readmission after TPIAT is common (one in four patients), underscoring the complexity of this procedure. Early readmission is not detrimental to islet graft function. Patients undergoing pylorus preservation are more likely to get readmitted, perhaps due to increased incidence of delayed gastric emptying. Decision for antrectomy vs. pylorus preservation needs to be individualized. PMID- 28993045 TI - [The pharmaceutical industry and specialised medical training: Residents' perceptions in Madrid, Spain]. AB - OBJECTIVE: To assess the frequency of exposure and attitudes to the pharmaceutical industry (PI) of residents in the Region of Madrid (RM), Spain, and to analyse the association with specialty, professional environment and training. METHODS: Cross-sectional electronic survey in May and June 2015 of all medical residents in RM. We collected sociodemographic variables and those of interaction with the PI in four blocks: frequency of interactions, attitudes and perceptions, environment and regulatory framework, and skills; with the first two blocks we created a Synthetic PI Interaction Index (SPIII). Bivariate and multivariate analysis of logistic regression. RESULTS: 350 resident's responses (28% family and community medicine [FCM], 57% hospital, 15% others). Ninety-eight percent reported interacting with the PI. Twenty percent believed their prescribing was influenced by the PI and 48% believed it was influenced by other doctors. Sixty-five precent considered more training necessary. Ninety-six percent had received no information from their college of physicians, 80% did not know the regulations in their medical society and 50% were unaware of those of their institution. Hospital specialty residents showed more likelihood of SPIII >= percentile 75 than those of FCM (odds ratio [OR]: 3.96; 95% confidence interval [95%CI]: 1.88-8.35). Training in informal settings was associated with SPIII <= percentile 25 (OR: 2.83; 95%CI: 1.32-6.07). CONCLUSIONS: The medical residents in RM had a high level of interaction with the PI and believed its influence low. Hospital specialty residents showed more interaction with the PI. Regulations were not well known by residents and they consideredmore training necessary. PMID- 28993046 TI - The experience of intensive care nurses caring for patients with delirium: A phenomenological study. AB - OBJECTIVES: The purpose of this research was to seek to understand the lived experience of intensive care nurses caring for patients with delirium. The objectives of this inquiry were: 1) To examine intensive care nurses' experiences of caring for adult patients with delirium; 2) To identify factors that facilitate or hinder intensive care nurses caring for these patients. RESEARCH METHODOLOGY: This study utilised an interpretive phenomenological approach as described by van Manen. SETTING: Individual conversational interviews were conducted with eight intensive care nurses working in a tertiary level, university-affiliated hospital in Canada. FINDINGS: The essence of the experience of nurses caring for patients with delirium in intensive care was revealed to be finding a way to help them come through it. Six main themes emerged: It's Exhausting; Making a Picture of the Patient's Mental Status; Keeping Patients Safe: It's aReally Big Job; Everyone Is Unique; Riding It Out With Families and Taking Every Experience With You. CONCLUSION: The findings contribute to an understanding of how intensive care nurses help patients and their families through this complex and distressing experience. PMID- 28993047 TI - The Minimally Invasive Approach to Left Ventricular Assist Device Implantation: Is Smaller Better? PMID- 28993049 TI - Prestroke Mobility and Dementia as Predictors of Stroke Outcomes in Patients Over 65 Years of Age: A Cohort Study From The Swedish Dementia and Stroke Registries. AB - OBJECTIVES: To explore the association between prestroke mobility dependency and dementia on functioning and mortality outcomes after stroke in patients>65 years of age. DESIGN: Longitudinal cohort study based on SveDem, the Swedish Dementia Registry and Riksstroke, the Swedish Stroke Registry. PARTICIPANTS: A total of 1689 patients with dementia >65 years of age registered in SveDem and suffering a first stroke between 2007 and 2014 were matched with 7973 controls without dementia with stroke. MEASUREMENTS: Odds ratios (ORs) and 95% confidence intervals (CIs) for intrahospital mortality, and functioning and mortality outcomes at 3 months were calculated. Functioning included level of residential assistance (living at home without help, at home with help, or nursing home) and mobility dependency (independent, needing help to move outdoors, or needing help indoors and outdoors). RESULTS: Prestroke dependency in activities of daily living and mobility were worse in patients with dementia than controls without dementia. In unadjusted analyses, patients with dementia were more often discharged to nursing homes (51% vs 20%; P < .001). Mortality at 3 months was higher in patients with dementia (31% vs 23% P < .001) and fewer were living at home without help (21% vs 55%; P < .001). In adjusted analyses, prestroke dementia was associated with higher risk of 3-month mortality (OR 1.34; 95% CI 1.18-1.52), requiring a higher level of residential assistance (OR 4.07; 3.49 .75) and suffering from more dependency in relation to mobility (OR 2.57; 2.20 3.02). Patients with dementia who were independent for mobility prestroke were more likely to be discharged to a nursing home compared with patients without dementia with the same prestroke mobility (37% vs 16%; P < .001), but there were no differences in discharge to geriatric rehabilitation (19% for both; P = .976). Patients, who moved independently before stroke, were more often discharged home (60% vs 28%) and had lower mortality. In adjusted analyses, prestroke mobility limitations were associated with higher odds for poorer mobility, needing more residential assistance, and death. CONCLUSIONS: Patients with mobility impairments and/or dementia present a high burden of disability after a stroke. There is a need for research on stroke interventions among these populations. PMID- 28993048 TI - Total Physical Activity, Exercise Intensity, and Walking Speed as Predictors of All-Cause and Cause-Specific Mortality Over 7 Years in Older Men: The Concord Health and Aging in Men Project. AB - OBJECTIVE: The study aimed to examine the contemporaneous temporal association between changes in total physical activity, sports intensity, muscle strengthening exercise, and walking speed as predictors of all-cause, cardiovascular, cancer and other cause-specific mortality in older men. DESIGN, SETTING, PARTICIPANTS, MEASUREMENTS: Community-dwelling men aged 70 years and older from Concord Health and Aging in Men Project were assessed at baseline (2005-2007, n = 1705), 2 years (n = 1367), and 5 years follow-up (n = 958). At all time points, Physical Activity Scale for the Elderly questionnaire, walking speed over a 6-m walk, and potential confounders were assessed. Mortality was ascertained through the state death registry with a median follow-up of 7 years. RESULTS: As the Physical Activity Scale for the Elderly score increased by 1 standard deviation over the follow-up period, the relative risk (RR) for mortality was 0.78 [95% confidence interval (CI) 0.69-0.88] for all-cause, 0.66 (95% CI 0.55-0.79) for cardiovascular and 0.75 (95% CI 0.61-0.94) for other cause specific mortality, but no association was observed in cancer mortality. The RR for undertaking strenuous sports during follow-up was 0.44 (95% CI 0.26-0.72) for all-cause mortality and 0.31 (95% CI 0.13-0.70) for cancer mortality when compared with no sports participation. Increases in walking speed per standard deviation over time were also associated with a decrease in all-cause mortality (RR 0.69, 95% CI 0.61-0.78), with similar associations for cardiovascular (RR 0.60, 95% CI 0.48-0.74), but not cancer mortality. CONCLUSIONS: Older men who engage in strenuous sports and those who increase their walking speed over time may have lower risk of all-cause and some cause-specific mortality. PMID- 28993050 TI - Sulfonamido-derivatives of unsubstituted carbazoles as BACE1 inhibitors. AB - A novel series of variously substituted N-[3-(9H-carbazol-9-yl)-2-hydroxypropyl] arylsulfonamides has been synthesized and assayed for beta-Secretase (BACE1) inhibitory activity. BACE1 is a widely recognized drug target for the prevention and treatment of Alzheimer's Disease (AD). The introduction of benzyl substituents on the nitrogen atom of the arylsulfonamide moiety has so far led to the best results, with three derivatives showing IC50 values ranging from 1.6 to 1.9 MUM. Therefore, a significant improvement over the previously reported series of N-carboxamides (displaying IC50's >= 2.5 MUM) has been achieved, thus suggesting an active role of the sulfonamido-portion in the inhibition process. Preliminary molecular modeling studies have been carried out to rationalize the observed structure-activity relationships. PMID- 28993051 TI - Isolating automatic photism generation from strategic photism use in grapheme colour synaesthesia. AB - Grapheme-colour synaesthesia is a phenomenon in which ordinary black numbers and letters (graphemes) trigger the experience of highly specific colours (photisms). The Synaesthetic Stroop task has been used to demonstrate that graphemes trigger photisms automatically. In the standard Stroop task, congruent trial probability (CTP) has been manipulated to isolate effects of automaticity from higher-order strategic effects, with larger Stroop effects at high CTP attributed to participants strategically attending to the stimulus word to facilitate responding, and smaller Stroop effects at low CTP reflecting automatic word processing. Here we apply this logic for the first time to the Synaesthetic Stroop task. At high CTP we showed larger Stroop effects due to synaesthetes using their synaesthetic colours strategically. At low CTP Stroop effects were reduced but were still significant. We directly isolate automatic processing of graphemes from strategic effects and conclusively show that, in synaesthesia, viewing black graphemes automatically triggers colour experiences. PMID- 28993052 TI - Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO 4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. AB - BACKGROUND: Patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, two or more previous regimens of chemotherapy have a poor prognosis, and current guidelines do not recommend any specific treatments for these patients. We assessed the efficacy and safety of nivolumab, a fully human IgG4 monoclonal antibody inhibitor of programmed death-1 (PD-1), in patients with advanced gastric or gastro-oesophageal junction cancer who had been previously been treated with two or more chemotherapy regimens. METHODS: In this randomised, double-blind, placebo-controlled, phase 3 trial done at 49 clinical sites in Japan, South Korea, and Taiwan, eligible patients (aged >=20 years with unresectable advanced or recurrent gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, standard therapy [including two or more previous chemotherapy regimens], with an Eastern Cooperative Oncology Group [ECOG] performance status of 0-1, and naive to anti-PD-1 therapy or other therapeutic antibodies and pharmacotherapies for the regulation of T cells) were recruited. Patients were randomly assigned (2:1) using an interactive web response system to receive 3 mg/kg nivolumab or placebo intravenously every 2 weeks, stratified by country, ECOG performance status, and number of organs with metastases. Study treatment was continued until progressive disease per investigator assessment or onset of toxicities requiring permanent discontinuation. Patients and investigators were masked to group assignment. The primary endpoint was overall survival in the intention-to-treat population. Safety was analysed in all patients who received at least one dose of study treatment. This study is ongoing but not recruiting new patients, and is registered with ClinicalTrials.gov, number NCT02267343. FINDINGS: Between Nov 4, 2014, and Feb 26, 2016, we randomly assigned 493 patients to receive nivolumab (n=330) or placebo (n=163). At the data cutoff (Aug 13, 2016), median follow-up in surviving patients was 8.87 months (IQR 6.57-12.37) in the nivolumab group and 8.59 months (5.65-11.37) in the placebo group. Median overall survival was 5.26 months (95% CI 4.60-6.37) in the nivolumab group and 4.14 months (3.42-4.86) in the placebo group (hazard ratio 0.63, 95% CI 0.51-0.78; p<0.0001). 12-month overall survival rates were 26.2% (95% CI 20.7-32.0) with nivolumab and 10.9% (6.2-17.0) with placebo. Grade 3 or 4 treatment-related adverse events occurred in 34 (10%) of 330 patients who received nivolumab and seven (4%) of 161 patients who received placebo; treatment related adverse events led to death in five (2%) of 330 patients in the nivolumab group and two (1%) of 161 patients in the placebo group. No new safety signals were observed. INTERPRETATION: In this phase 3 study, the survival benefits indicate that nivolumab might be a new treatment option for heavily pretreated patients with advanced gastric or gastro-oesophageal junction cancer. Ongoing trials that include non-Asian patients are investigating nivolumab for advanced gastric or gastro-oesophageal junction cancer in various settings and earlier treatment lines. FUNDING: Ono Pharmaceutical and Bristol-Myers Squibb. PMID- 28993053 TI - Checkpoint inhibition: an ATTRACTION in advanced gastric cancer? PMID- 28993054 TI - Near-infrared spectroscopy (NIRS) for a real time monitoring of the biogas process. AB - In this research project Near-infrared spectroscopy (NIRS) was applied to monitor the content of specific process parameters in anaerobic digestion. A laboratory scaled biogas digester was constantly fed every four hours with maize- and grass silage to keep a base load with an organic loading rate (OLR) of 2.5 kg oDM/m3 * d. Daily impact loads with shredded wheat up to an OLR of 8 kg oDM/m3 * d were added in order to generate peaks at the parameters tested. The developed calibration models are capable to show changes in process parameters like volatile fatty acids (VFA), propionic acid, total inorganic carbon (TIC) and the ratio of the volatile fatty acids to the carbonate buffer (VFA/TIC). Based on the calibration of the models for VFA and TIC, the values could be predicted with an R2 of 0.94 and 0.97, respectively. Moreover, the residual prediction deviations were 4.0 and 6.0 for VFA and TIC, respectively. PMID- 28993055 TI - Lignocellulosic biorefinery as a model for sustainable development of biofuels and value added products. AB - A constant shift of society's dependence from petroleum-based energy resources towards renewable biomass-based has been the key to tackle the greenhouse gas emissions. Effective use of biomass feedstock, particularly lignocellulosic, has gained worldwide attention lately. Lignocellulosic biomass as a potent bioresource, however, cannot be a sustainable alternative if the production cost is too high and/ or the availability is limited. Recycling the lignocellulosic biomass from various sources into value added products such as bio-oil, biochar or other biobased chemicals in a bio-refinery model is a sensible idea. Combination of integrated conversion techniques along with process integration is suggested as a sustainable approach. Introducing 'series concept' accompanying intermittent dark/photo fermentation with co-cultivation of microalgae is conceptualised. While the cost of downstream processing for a single type of feedstock would be high, combining different feedstocks and integrating them in a bio-refinery model would lessen the production cost and reduce CO2 emission. PMID- 28993056 TI - Role of 18F-PET/CT in Predicting Prognosis of Patients With Breast Cancer After Neoadjuvant Chemotherapy. AB - BACKGROUND: Breast cancer can be assessed preoperatively and postoperatively using 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). We prospectively analyzed the maximum baseline standardized uptake value (SUVmax) derived from FDG PET/CT to predict the outcomes after neoadjuvant chemotherapy (NAC) for breast cancer. PATIENTS AND METHODS: We assessed 130 consecutive female patients with primary breast cancer (mean age, 53.9 years) using PET/CT before and after NAC. The SUVmax before (pre-SUVmax) and after (post-SUVmax) NAC and the SUVmax reduction rates (DeltaSUVmax) after NAC with sequential anthracyclines and a taxane were assessed to predict the pathologic complete response (pCR) and prognosis. RESULTS: Of the 130 patients, 30 (23.1%) achieved a pCR. The pCR rate of the patients with human epidermal growth factor receptor 2-positive (HER2+) and triple-negative (TN) breast cancer was 52.8% and 40.0%, respectively. In contrast, only 1.4% of those with estrogen receptor-positive and HER2- cancer achieved a pCR. The post-SUVmax correlated closely with the pCR (area under the curve, 0.700) but not with the pre-SUVmax and DeltaSUVmax (area under the curve, 0.414 and 0.589, respectively) in patients with HER2+ and TN breast cancer. The post-SUVmax was associated with the pCR (P = .019), and multivariate analysis selected post-SUVmax as a significant prognostic factor (P = .014). The post-SUVmax correlated significantly with recurrence-free survival and recurrence (P = .026, log-rank test). CONCLUSION: The SUVmax determined after NAC using FDG PET/CT can predict for the pCR and the prognosis of patients with operable HER2+ and TN breast cancer. In the future, additional chemotherapy will be applied according to the post-SUVmax after standard NAC to achieve a pCR or omit surgery. PMID- 28993057 TI - Solitary pancreatic lesion as the initial metastasis from osteosarcoma: Report of a rare case. PMID- 28993058 TI - Pathological heterogeneity in sporadic synchronous renal tumors: Is the histological concordance predictable? AB - OBJECTIVE: To evaluate the pathological concordance rate of multiple synchronous renal masses (MSRM) presumed to be sporadic and to analyze predictive factors of concordance. MATERIAL AND METHODS: We identified from our institutional database patients with sporadic MSRM treated at our center between January 2000 and December 2015. All tumors were reviewed by a dedicated uropathologist. Pathological concordance rate was analyzed regarding clinical characteristics and preoperative imaging. RESULTS: We included 112 patients: 50 had unilateral synchronous renal masses and 62 bilateral synchronous renal masses. A total of 291 tumors were analyzed, with an average of 2.6 tumors per patient. Overall, the malignant concordance rate was 91.6%, the pathological concordance rate was 67.3% and the grade concordance rate was 62.5%. In univariate analysis, predictive factors of histological concordance were bilateral synchronous renal masses (odds ratio [OR] = 3.39; 95% CI: 1.06-10.8; P = 0.04), age<60 years (OR = 3.04; 95% CI: 1.2-7.7; P = 0.02) and >=3 lesions (OR = 2.41; 95% CI: 1.03-5.68; P = 0.04). In multivariate analysis, age<60 remained significantly associated with histological concordance (OR = 3.84; 95% CI: 1.24-11.9; P = 0.02). CONCLUSIONS: The histological concordance rate of MSRM is low. Age at diagnosis <60 years, bilateral lesions and >=3 tumors are predictive factors of histological concordance, but the pathological diagnosis remains difficult to predict. This heterogeneity is important to take into account, particularly when choosing the treatment upon the renal biopsy results from a single lesion. PMID- 28993059 TI - Perioperative blood transfusion adversely affects prognosis after nephrectomy for renal cell carcinoma. AB - BACKGROUND: It has been previously suggested that perioperative blood transfusion (PBT) may induce adverse oncological outcomes following cancer surgery. The aim of the current study is to evaluate the effect of PBT on the prognosis of patients who underwent nephrectomy due to renal cell carcinoma (RCC). METHODS: Study included 1,159 patients who underwent radical nephrectomy or partial nephrectomy (PN) between the years 1987 and 2013. Univariate and multivariate models were used to evaluate the association of PBT with cancer-specific survival (CSS), disease-free survival, and overall survival (OS). RESULTS: Of 1,159 patients undergoing nephrectomy, 198 patients (17.1%) received a PBT. The median follow-up was 63.2 months. Risk factors for PBT included: lower preoperative hemoglobin (P<0.01), size of the renal mass (P<0.05), open surgical approach (P<0.01), and capsular invasion. Receipt of a PBT was associated with significantly adverse disease-free survival (hazard ratio [HR] = 2.1, P = 0.02), metastatic progression (HR = 2.4, P= 0.007), CSS (HR = 2.5, P = 0.02), and OS (HR = 2.2, P = 0.001). In the current study, 582 patients underwent PN; of these, 87 (14.9%) required PBT. The association of PBT with outcome remained significant in this subgroup after controlling for patient and tumor-related variables with respect to metastatic progression (HR = 5.9, P = 0.006), CSS (HR = 5.8, P = 0.007) and OS (HR = 2.1, P = 0.05). CONCLUSION: PBT is associated with reduced recurrence-free survival, CSS, and OS in patients undergoing nephrectomy for RCC. Worse oncological outcomes are also found in a separate analysis for patients undergoing PN. PMID- 28993060 TI - Routine bladder cancer treatment dictates divergence from trial-derived regimens: Results of treatment at 44 radiotherapy centers. AB - PURPOSE: To assess characteristics and outcome of patients treated with radiotherapy for muscle-invasive bladder cancer at 44 community-based radiotherapy centers and compare these to those on clinical trials. MATERIALS AND METHODS: We reviewed 155 patients who had been treated from 2010 to 2014. Overall survival and progression-free survival were estimated using the Kaplan-Meier method. Results were compared to a pooled analysis of 6 Radiation Therapy Oncology Group (RTOG) protocols. RESULTS: What stood out was that our patients' characteristics were significantly inferior than those on RTOG studies: lower rate of complete transurethral resection of bladder tumor: 36.8% vs. 70% (P<0.0001), higher median age: 79 years vs. 66 (P<0.0001), more medically inoperable: (51.0%) vs. 0% in RTOG (P<0.001), and 46.9% had refused surgery. Fewer patients underwent concurrent chemotherapy: 56.1% vs. 100% (P<0.0001). It was also striking that at median follow-up 12.6 months (range: 3.1-49.2), the 36 month overall survival was 51.3% for those who refused surgery vs. 24.5% for medically inoperable (P = 0.009); 58.1% with complete transurethral resection of bladder tumor vs. 29.8% if incomplete (P = 0.07); 54.3% with chemoradiotherapy (CRT) vs. 17.2% without (P = 0.03); 66.3% for those who refused surgery and had CRT vs. 38.9% for medically inoperable who had CRT (P = 0.04). CONCLUSIONS: The cohort at community-based centers was older, more medically inoperable, and less likely to receive CRT than clinical trial patients. This suggests that we may not be able to apply trial-derived regimens for many patients in this setting. There is a pressing need to find treatment options for such patients, especially given the aging population. Survival of medically operable CRT patients was comparable to results of RTOG protocols notwithstanding this study's smaller sample size, retrospective nature and suboptimal documentation of patient characteristics. PMID- 28993062 TI - Chronic spontaneous urticaria and the extrinsic coagulation system. AB - Chronic spontaneous urticaria (CSU) is a common skin disorder characterized by daily or almost daily recurring skin edema and flare with itch. Recently, the activation of the blood coagulation cascade has been suggested to be involved in CSU, but the trigger of the coagulation cascade remains unclear. In this article, we review recent understanding of the relationship between the pathogenesis of CSU and extrinsic coagulation reactions. In CSU, vascular endothelial cells and eosinophils may play a role as TF-expressing cells for activating the extrinsic coagulation pathway. Moreover, the expression of TF on endothelial cells is synergistically enhanced by the activation of Toll-like receptors and histamine H1 receptors. The activated coagulation factors may induce plasma extravasation followed by degranulation of skin mast cells and edema formation recognized as wheal in CSU. Molecules involved in this cascade could be a target for new and more effective treatments of urticaria. PMID- 28993063 TI - Comparison of sporadic cases of Salmonella Typhimurium with other Salmonella serotypes in Castellon (Spain): case-case study. AB - INTRODUCTION: Salmonella infections (SI) are common in Spain. The aim of this study was to appraise risk factors and the clinical characteristics of sporadic Salmonella Typhimurium infections compared with other sporadic salmonella serotype infections (OSI). METHODS: From September 2014 to August 2015, a case case study was carried out by the Epidemiology Division of the Public Health Centre of Castellon. Case 1 consisted of patients with sporadic S. Typhimurium infections, while case 2 comprised OSI patients, assessed according to the stool cultures analyzed by the Microbiology Laboratories of Hospital General de Castellon and Hospital de La Plana in Vila-real. Patients from detected outbreaks were not included. The salmonella serotype was identified by the National Centre of Microbiology (Madrid). RESULTS: The total number of SI patients reported was 327, 242 of whom were studied (74.0%). 148 patients had sporadic S. Typhimurium infection and 64 had OSI, with median ages of 4 and 8.5 years, respectively. Sporadic S. Typhimurium infection patients presented more blood in feces and diarrhea episodes. Consumption of pork meat (OR=2.22; 95% CI 1.12-4.43), cold pork meats (OR=2.49; 95% CI 1.32-4.68) and playing in the dirt (OR=3.02; 95% CI 1.55-5.88), were associated with sporadic S. Typhimurium infection. In the 0-4 year-old group, the associated factors were consumption of cold pork meats, omelets and female gender. In the 5-year-old and over group, only playing in soil was associated with sporadic S. Typhimurium infection. CONCLUSIONS: The consumption of pork and omelets, as well as playing in the dirt, were the main factors associated with infection. Children were most affected by sporadic S. Typhimurium infection. PMID- 28993064 TI - Antimicrobial susceptibility of microorganisms that cause urinary tract infections in pediatric patients. AB - INTRODUCTION: Cumulative susceptibility reports are a valuable tool for the empirical treatment of urinary tract infections, especially in the current context of increasing resistance rates. Our objective was to analyze the antimicrobial susceptibility of bacterial isolates in urine cultures of pediatric patients during a five-year period. METHODS: Retrospective study of urine cultures from 2011 to 2015. Identification and antimicrobial susceptibility tests were performed using the Vitek-2 system (BioMerieux(r)) and categorized according to EUCAST criteria. Antimicrobial susceptibility data were analyzed by gender and age groups (neonates, 1 month to 5 years, 5-15 years) before being compared with data obtained from patients over the age of 15 years. RESULTS: During the study period, 17164 urine cultures were processed from 7924 patients under 16 years of age. Antimicrobial susceptibility rates in these patients were: ampicillin 36.3%, amoxicillin/clavulanic acid 75.3%, cefuroxime 83.2%, co-trimoxazole 68.9%, ciprofloxacin 85.3%, fosfomycin 85.5%, nitrofurantoin 84.4% and 3rd generation cephalosporins 89-91%. Aminoglycosides (>92%) and carbapenems (95%) maintained the highest susceptibility rates. The prevalence of ESBL-producing isolates was significantly lower in children under the age of 16 years (1.5% vs. 4.1%). In patients under the age of 16 years, Escherichia coli isolates in girls were significantly more sensitive (p<0.0001) to ampicillin (41% vs. 30%) and amoxicillin/clavulanic acid (82% vs. 72%) than in boys. CONCLUSIONS: The compilation of cumulative susceptibility reports disaggregated by age or gender reveals significant differences. In our setting, cefuroxime may be considered the first-line empirical treatment in pediatric patients. PMID- 28993061 TI - Risk comparison for prenatal use of analgesics and selected birth defects, National Birth Defects Prevention Study 1997-2011. AB - PURPOSE: To compare the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and/or opioids to the use of acetaminophen without NSAIDs or opioids with respect to associations with birth defects. METHODS: We used data from the National Birth Defects Prevention Study (1997-2011). Exposure was self-reported maternal analgesic use from the month before through the third month of pregnancy (periconceptional). Adjusted odds ratios (aORs) were calculated to examine associations with 16 birth defects. RESULTS: Compared to acetaminophen, mothers reporting NSAIDs were significantly more likely to have offspring with gastroschisis, hypospadias, cleft palate, cleft lip with cleft palate, cleft lip without cleft palate, anencephaly, spina bifida, hypoplastic left heart syndrome, pulmonary valve stenosis, and tetralogy of Fallot (aOR range, 1.2-1.6). Opioids were associated with tetralogy of Fallot, perimembranous ventricular septal defect, and ventricular septal defect with atrial septal defect (aOR range, 1.8 2.3), whereas use of both opioids and NSAIDs was associated with gastroschisis, cleft palate, spina bifida, hypoplastic left heart syndrome, and pulmonary valve stenosis (aOR range, 2.0-2.9). CONCLUSIONS: Compared to periconceptional use of acetaminophen, selected birth defects occurred more frequently among infants of women using NSAIDs and/or opioids. However, we could not definitely determine whether these risks relate to the drugs or to indications for treatment. PMID- 28993065 TI - Percutaneous bone biopsy is different to per-wound bone biopsy. Comments on "Diabetic foot osteomyelitis: Is conservative treatment possible?". PMID- 28993066 TI - Clinical and microbiological profile of infectious keratitis in an area of Madrid, Spain. AB - INTRODUCTION: To study antibiotic susceptibility in bacterial keratitis (BK), its profile over 10 years and its influence on ophthalmological practice. METHODS: Retrospective review of BK with positive corneal scraping over a 10-year period. Risk factors for keratitis, visual acuity (VA), empirical topical treatment, corneal infection characteristics and outcomes were analyzed for BK due to Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Pseudomonas aeruginosa and Propionibacterium acnes. RESULTS: 389 positive corneal scrapings were collected. All Gram-positive bacteria were susceptible to vancomycin. P. aeruginosa demonstrated >90% sensitivity to the most-commonly-used topical antibiotics. Susceptibility to methicillin was 90.2% for S. aureus and 66.3% for S. epidermidis. The results of 215 patients were available. 1.9% required enucleation and 2.8% required surgical treatments. Final VA improved after treatment in keratitis due to S. aureus (p=0.026) and S. epidermidis (p=0.005). There was a correlation between S. aureus resistance to methicillin (p=0.002) and levofloxacin (p=0.043) and enucleation (20% and 10%, respectively) compared with a 0% rate of enucleation in S. aureus-susceptible keratitis. CONCLUSIONS: BK due to S. pneumoniae is very aggressive irrespective of antibiotic sensitivity. S. aureus was frequently isolated in patients with systemic diseases. It causes severe keratitis and remains moderately resistant to methicillin and levofloxacin. For this reason, keeping vancomycin in empirical regimens is believed to be necessary. PMID- 28993067 TI - The use of co-trimoxazole in catheter lock therapy. A report on a difficult case. PMID- 28993068 TI - Indicator condition based HIV testing: Missed opportunities for earlier diagnosis in men who have sex with men. AB - INTRODUCTION: Contact with the healthcare system by a sample of seropositive men who have sex with men (MSM) prior to their HIV diagnosis are analysed, and missed opportunities (MO) for an earlier HIV diagnosis are identified. METHODOLOGY: Between 2012-2013, an online survey was conducted among HIV-positive MSM, mainly recruited from gay websites. Those who were diagnosed with HIV between 2010-2013 were analysed. MO were defined as episodes prior to the HIV diagnosis in which the healthcare system was contacted due to an indicator condition of HIV infection and the test was not suggested. The proportion of missed opportunities were compared according to the type of indicator condition, the department consulted and the healthcare professional's knowledge that the patient was MSM. RESULTS: Overall, 639 participants (66% of 966) reported 1,145 episodes with some indicator condition, the majority of these being identified in primary care (n=527; 46%). The highest percentage of MOs is also observed in primary care (63%). Although the indicator condition with the highest number of MOs was STIs (n=124), the highest percentage of MOs was observed in consultations due to diarrhoea with no known cause (69.8%). The percentage of MOs when the doctor knew that the patient was MSM was 40 vs. 70% when the doctor did not know. CONCLUSION: The majority of HIV-positive MSM analysed in this study went to healthcare services for HIV-infection indicator conditions prior to their HIV diagnosis. Primary care was the most-frequently-visited department and is also where the most opportunities were missed to perform an HIV test, even when it was known that the patient was a MSM. PMID- 28993069 TI - Discrimination of subjective responses between contact lenses with a novel questionnaire. AB - PURPOSE: To describe a ranked symptoms scale (RSS) discriminating subjective responses in contact lens (CL) wear in various situations. METHOD: Forty experienced clinical trial participants were interviewed for their perceptions of ocular comfort scales, resulting in a numerical RSS. For further evaluation, 20 CL wearers enrolled into a prospective, randomised, crossover trial. Two silicone hydrogel CLs and a lens care solution (LCS) [Combinations A & B] were selected based on prior performance identifying best/worst combinations for end-of-day comfort. The RSS and a numerical rating scale (NRS) were administered at two time points (insertion/removal) on alternating days for 6 days. RESULTS: Both NRS and RSS showed acceptable internal consistency for comfort, vision and handling (Cronbach alpha=0.71 for both scales) and similar repeatability for comfort and handling (coefficients-of-repeatability within 0.1 and 0.2 units, respectively, for each scale). The NRS and RSS discriminated differences between combinations for comfort (p<=0.031) and vision (p<=0.026) at both time-points. Additionally, the RSS showed lens/edge awareness influenced discomfort the most, ranking higher at insertion (p=0.038) and higher for Combination-B at both time-points (p<=0.002). Symptoms of dryness and tired eyes increased for both combinations at removal (p<0.02). The RSS also showed haziness and blurred distance vision influenced vision dissatisfaction with Combination-B at lens removal (p<=0.038) while eye strain/headache increased for both combinations by time of removal (p<=0.013). CONCLUSIONS: The RSS is able to discriminate subjective responses between combinations and time-of-day. The RSS's ability to rank symptoms may be a useful tool in understanding perceptions of discomfort or dissatisfaction with CL wear. PMID- 28993070 TI - The effect of soft contact lens thickness in visual function after intracorneal ring segments surgery. AB - OBJECTIVE: To study the influence of soft contact lens (SCL) central thickness and material in keratoconus on visual function after intracorneal ring segment (ICRS) surgery. METHODS: A pilot, experimental, prospective, cross-sectional and double-blind study was performed. Fourteen keratoconus patients with age range of 34.75+/-9.22years (7 males and 7 females) with ICRS implanted were involved in the study. Two different SCL materials [Hioxifilcon A (G-5X/p-GMA/HEMA) and Lucifilcon A (silicone-hydrogel)] with four different central thicknesses (0.1, 0.2, 0.3 and 0.4mm) were fitted in one eye per patient, selected randomly. High and low corrected distance visual acuity (CDVA) and contrast sensitivity (CS), corneal topography and corneal and total aberrometry were measured. RESULTS: Corneal spherical like, coma like and root mean square (RMS) decreased significantly for 0.3 and 0.4mm in both SCL materials (p<0.05). Total RMS decreased significantly for 0.4mm with both SCL materials (p<0.05). High and low CDVA improved for 0.4mm of thickness for both materials (p<0.05). Statistically increasing were found in all thicknesses studied for CS in both materials (p<0.05). CONCLUSION: A central thickness of the SCL equal or superior to 0.4mm seems to decrease the ocular high order aberration (HOA) and to improve the visual function in keratoconus patients implanted with ICRS. However, the modulus of rigidity of the SCL would not influence the HOA correction. PMID- 28993071 TI - RE: Park YM. Park YK. Lee JE & Lee JS. Effect of orthokeratology in patients with myopic regression after refractive surgery. CLAE (2016; 39(2):167-71). PMID- 28993072 TI - A rare cause of recurrent intestinal obstruction. PMID- 28993073 TI - The use of cannabis in response to the opioid crisis: A review of the literature. AB - BACKGROUND: A staggering number of Americans are dying from overdoses attributed to prescription opioid medications (POMs). In response, states are creating policies related to POM harm reduction strategies, overdose prevention, and alternative therapies for pain management, such as cannabis (medical marijuana). However, little is known about how the use of cannabis for pain management may be associated with POM use. PURPOSE: The purpose of this article is to examine state medical cannabis (MC) use laws and policies and their potential association with POM use and related harms. METHODS: A systematic literature review was conducted to explore United States policies related to MC use and the association with POM use and related harms. Medline, PubMed, CINAHL, and Cochrane databases were searched to identify peer-reviewed articles published between 2010 and 2017. Using the search criteria, 11,513 records were identified, with 789 abstracts reviewed, and then 134 full-text articles screened for eligibility. FINDINGS: Of 134 articles, 10 articles met inclusion criteria. Four articles were cross sectional online survey studies of MC substitution for POM, six were secondary data analyses exploring state-level POM overdose fatalities, hospitalizations related to MC or POM harms, opioid use disorder admissions, motor vehicle fatalities, and Medicare and Medicaid prescription cost analyses. The literature suggests MC laws could be associated with decreased POM use, fewer POM-related hospitalizations, lower rates of opioid overdose, and reduced national health care expenditures related to POM overdose and misuse. However, available literature on the topic is sparse and has notable limitations. CONCLUSIONS: Review of the current literature suggests states that implement MC policies could reduce POM-associated mortality, improve pain management, and significantly reduce health care costs. However, MC research is constrained by federal policy restrictions, and more research related to MC as a potential alternative to POM for pain management, MC harms, and its impact on POM-related harms and health care costs should be a priority of public health, medical, and nursing research. PMID- 28993075 TI - Call to action: APRNs in U.S. nursing homes to improve care and reduce costs. AB - BACKGROUND: Centers for Medicare and Medicaid Innovation Center sponsored the initiative to reduce avoidable hospitalizations among nursing facility residents. PURPOSE: Missouri Quality Initiative (MOQI) designed inter-professional model in nursing homes with advanced practice registered nurses (APRNs). METHOD: MOQI APRN model was implemented for 4 years in 16 nursing homes in a metro area of the Midwest. Hospitalizations were reduced (40% all-cause, 58% potentially avoidable), emergency room visits (54% all-cause, 65% potentially avoidable), Medicare expenditures for hospitalizations (34% all-cause, 45% potentially avoidable), and Medicare expenditures for emergency room visits (50% all-cause, 60% potentially avoidable) for long-stay nursing home residents. DISCUSSION: Success of the MOQI model reinforces decades of research demonstrating that care provided by APRNs is cost-effective, safe, and associated with positive health outcomes and patient satisfaction. CONCLUSION: Nursing homes can implement and benefit by hiring APRNs. However, changes in the Code of Federal Regulation (CFR 483.40) are necessary to improve patient access to care and encourage hiring APRNs in US nursing homes. PMID- 28993076 TI - Unicompartmental Knee Arthroplasty Achieves Greater Flexion With No Difference in Functional Outcome, Quality of Life, and Satisfaction vs Total Knee Arthroplasty in Patients Younger Than 55 Years. A Propensity Score-Matched Cohort Analysis. AB - BACKGROUND: Improvements in surgical techniques, implant design, and adherence to indications have resulted in favorable outcomes after unicompartmental knee arthroplasty (UKA), particularly in an older population. However, no studies have compared the performance of contemporary UKA and total knee arthroplasty (TKA) in a young population. METHODS: Prospectively collected registry data of 160 UKAs performed in 160 patients younger than 55 years were reviewed. Propensity scores generated using logistic regression were used to adjust for confounding variables of age, gender, body mass index, preoperative range of motion, Knee Society Score, Oxford Knee Score, and Short-Form 36, allowing matching of the TKA cohort to the UKA cohort in a 1:1 ratio using the nearest-neighbor method. RESULTS: The UKA group had significantly greater flexion at 6 months and 2 years (P < .001). There was no significant difference in Knee Society Score, Oxford Knee Score, and Short-Form 36. At 2 years, 89.4% and 88.8% of the TKA and UKA groups were satisfied (P = 1.00) while 86.9% and 86.3% had their expectations fulfilled (P = 1.00). At a mean follow-up of 7 years, there were 2 revisions in each group (2.2%). CONCLUSION: Although native knee biomechanics are preserved, younger patients do not seem to perceive this oft-cited benefit of UKA, as this did not translate into greater health-related quality of life or patient satisfaction compared to TKA. The theoretical advantages of UKA were not borne out by our findings, other than greater flexion up to 2 years postoperatively. PMID- 28993074 TI - Obtaining waivers of parental consent: A strategy endorsed by gay, bisexual, and queer adolescent males for health prevention research. AB - BACKGROUND: Requiring parental consent in studies with sexual minority youth (SMY) can sometimes be problematic as participants may have yet to disclose their sexual orientation, may not feel comfortable asking parents' permission, and may promote a self-selection bias. PURPOSE: We discuss rationale for waiving parental consent, strategies to secure waivers from review boards, and present participants' feedback on research without parents' permission. METHODS: We share our institutional review board proposal in which we made a case that excluding SMY from research violates ethical research principles, does not recognize their autonomy, and limits collection of sexuality data. DISCUSSION: Standard consent policies may inadvertently exclude youth who are at high risk for negative health outcomes or may potentially put them at risk because of forced disclosure of sexual orientation. Securing a waiver addresses these concerns and allows for rich data, which is critical for providers to have a deeper understanding of their unique sexual health needs. CONCLUSION: To properly safeguard and encourage research informed by SMY, parental consent waivers may be necessary. PMID- 28993077 TI - Are We Appropriately Compensated by Relative Value Units for Primary vs Revision Total Hip Arthroplasty? AB - BACKGROUND: Relative value units (RVUs) are used to evaluate the effort required for providing a service to patients in order to determine compensation. Thus, more complicated cases, like revision arthroplasty cases, should yield a greater compensation. However, there are limited data comparing RVUs to the time required to complete the service. Therefore, the purpose of this study is to compare the (1) mean RVUs, (2) mean operative times, and (3) mean RVU/minute between primary and revision total hip arthroplasty (THA) and (4) perform an individualized idealized surgeon annual cost difference analysis. METHODS: A total of 103,702 patients who underwent primary (current procedural terminology code 27130) and 7273 patients who underwent revision THA (current procedural terminology code 27134) were identified using the National Surgical Quality Improvement Program database. Mean RVUs, operative times (minutes), and RVU/minute were calculated and compared using Student t-test. Dollar amount per minute, per case, per day, and year was calculated to find an individualized idealized surgeon annual cost difference. RESULTS: The mean RVU was 21.24 +/- 0.53 (range, 20.72-21.79) for primary and 30.27 +/- 0.03 (range, 30.13-30.28) for revision THA (P < .001). The mean operative time for primary THA was 94 +/- 38 minutes (range, 30-480 minutes) and 152 +/- 75 minutes (range, 30-475 minutes) for revision THA (P < .001). The mean RVU/minute was 0.260 +/- 0.10 (range, 0.04-0.73) for primary and 0.249 +/- 0.12 (range, 0.06-1.0) for revision cases (P < .001). The dollar amounts calculated for primary vs revision THA were as follows: per minute ($9.33 vs $8.93), per case ($877.12 vs $1358.32), per day ($6139.84 vs $5433.26), and a projected $113,052.28 annual cost difference for an individual surgeon. CONCLUSION: Maximizing the RVU/minute provides the greatest "hourly rate." The RVU/minute for primary (0.260) being significantly greater than revision THA (0.249) and an annualized $113,052.28 cost difference reveal that although revision THAs are more complex cases requiring longer operative time, greater technical skill, and aftercare, compensation per time is not greater. PMID- 28993078 TI - Response to Letter to the Editor on "Effectiveness of Bupivacaine Liposome Injectable Suspension for Postoperative Pain Control in Total Knee Arthroplasty: A Prospective, Randomized, Double Blind, Controlled Study". PMID- 28993079 TI - Lateral Femoral Epicondylar Osteotomy for Correction of Fixed Valgus Deformity in Total Knee Arthroplasty: A Technical Note. AB - BACKGROUND: Multiple surgical techniques exist to restore limb alignment and to balance soft tissues in valgus knees during total knee arthroplasty (TKA). One technique is to perform a lateral femoral epicondylar osteotomy. METHODS: A retrospective analysis was performed on all patients with a fixed valgus deformity that was corrected with a lateral femoral epicondylar osteotomy during TKA. Preoperative and postoperative Knee Society Knee Scores, knee stability, range of motion, and radiographic alignment were recorded. RESULTS: Ten patients (3 male and 7 female) underwent 12 TKAs by a single surgeon using a lateral femoral epicondylar osteotomy to correct a fixed valgus deformity. Implants used included 7 posterior stabilized, 3 constrained posterior stabilized, and 2 constrained condylar knees. Average age was 68 years (range 48-89) and average follow-up was 34.7 months (4-109). Average postoperative range of motion was 125 degrees of flexion (range 95 degrees -145 degrees ). The mean radiographic preoperative and postoperative anatomic tibiofemoral angles were 16.4 degrees of valgus (range 12 degrees -26 degrees ) and 5.5 degrees of valgus (range 4 degrees -7 degrees ), respectively. The mean preoperative knee society objective, satisfaction, expectation, and functional activity scores were 71, 20, 11, and 30, respectively. The mean postoperative knee society objective, satisfaction, expectation, and functional activity scores were 88, 34, 13, and 64, respectively. There was 1 postoperative deep vein thrombosis and 1 temporary peroneal nerve palsy. CONCLUSION: Lateral femoral epicondylar osteotomy is a useful technique to restore mechanical alignment in fixed valgus deformities in TKA. PMID- 28993080 TI - The Effect of Previous Coronary Artery Revascularization on the Adverse Cardiac Events Ninety days After Total Joint Arthroplasty. AB - BACKGROUND: Although coronary artery revascularization therapies are effective for treating coronary artery disease (CAD), these patients may be more susceptible to adverse cardiac events during later non-cardiac surgeries. The purpose of this study is to evaluate post-operative 90-day complications of total joint arthroplasty (TJA) in CAD patients with a history of CAD and to study the risk factors for cardiac complications. METHODS: We performed a retrospective analysis of TJA patients between 2005 and 2015 at our institute by summarizing the history of CAD, cardiac revascularization, and cardiac complications within 90 days after the operation. Multivariate logistic regression was performed to identify the factors that predicted cardiac complications within 90 days after the operation. RESULTS: A total of 4414 patients were included; of these, 64 underwent cardiac revascularization and 201 CAD patients underwent medical therapy other than revascularization. All the revascularization had history of myocardial infarction (MI). The rate of cardiac complications within 90 days for the CAD with revascularization was 18.7%, 18.4% for the CAD without revascularization, and 2.0% for the non-CAD group. A history of CAD and revascularization, bilateral TJA, general anesthesia, body mass index >=30 kg/m2, and history of MI were associated with a higher risk of cardiac complications. Patients who underwent TJA within 2 years after cardiac revascularization had a significantly higher cardiac complication rate, and the risk decreased with time. CONCLUSION: There is an increased risk of cardiac complications within 90 days after the operation among TJA patients with a history of CAD. Revascularization cannot significantly reduce the risk of cardiac complications after TJA for CAD patients. However, the risk decreased as the interval between revascularization and TJA increased. PMID- 28993081 TI - Letter to the Editor on "Effectiveness of Bupivacaine Liposome Injectable Suspension for Postoperative Pain Control in Total Knee Arthroplasty: A Prospective, Randomized, Double Blind, Controlled Study". PMID- 28993082 TI - Noncemented Total Hip Arthroplasty in Sickle-Cell Disease: Long-Term Results. AB - BACKGROUND: Avascular necrosis of the femoral head is a well-known sequela of sickle-cell disease (SCD) requiring a surgical intervention that comes with technical challenges. METHODS: Uncemented hip arthroplasty for avascular necrosis of the femoral head due to SCD was carried out for 101 patients (133 hips) between 2000 and 2012. The duration of follow-up ranged from 5 to 17 years (mean, 14.59 years). All patients received a noncemented femoral stem and a noncemented acetabular shell. RESULTS: After surgery, all patients showed improvement in their hip scores for pain, range of motion, and function. The 10-year survivorship was 98%. There were 6 intraoperative fractures of the proximal femur (4.5%), 4 superficial and 5 deep infections (6.77%), 1 aseptic shell failure (0.75%), and 1 aseptic femoral stem failure (0.75%). Brooker grade IV heterotopic ossification developed in 5 hips (3.76%). CONCLUSION: Hip arthroplasty in SCD is now a safe and effective procedure when the high rate of complications associated with this disease is given full consideration. With careful preoperative and postoperative planning, a highly successful outcome can be achieved. Noncemented shells and noncemented stems have shown durable long-term results. PMID- 28993083 TI - Acetabular Revision Arthroplasty Using an Uncemented Deep Profile Jumbo Component: A Ten to Sixteen Year Follow-Up Study. AB - BACKGROUND: The purpose of this study is to evaluate the outcome of revision total hip arthroplasty using an uncemented deep profile jumbo acetabular component in patients who had been followed for a minimum of 10 years postoperatively. METHODS: Between 1997 and 2001, 61 revision total hip arthroplasties were performed in 58 patients, with use of the +5 Deep Profile acetabular shell. The outcome with regard to retention vs re-revision of the acetabular component was determined for every hip. At a mean of 13 years (range 10-16) postoperatively, 30 patients (32 hips) were living. The Harris hip score, radiographic results, complications, and Kaplan-Meier survivorship were evaluated. RESULTS: In the entire cohort of 61 hips, 4 acetabular components have been re-revised. Two shells were re-revised for sepsis: 1 shell was re-revised for aseptic loosening and 1 for recurrent dislocation. In the 32 hips followed for a minimum of 10 years postoperatively, 2 cups have been re-revised: 1 for aseptic loosening and 1 for recurrent dislocation. One additional shell was loose by radiographic criteria. With failure defined as re-revision for any reason, implant survival (95% confidence interval) was 92.6% (81.0-97.2) at 16 years. With failure defined as re-revision for aseptic loosening, implant survival was 97.4% (82.8-99.6) at 16 years. CONCLUSION: Revision total hip arthroplasty with the +5 Deep Profile acetabular component was associated with a good rate of survival at 16 years. PMID- 28993084 TI - Perioperative Fractures in Cementless Total Hip Arthroplasty Using the Direct Anterior Minimally Invasive Approach: Reduced Risk With Short Stems. AB - BACKGROUND: The direct minimally invasive anterior approach (DMIAA) and the use of uncemented stems demonstrated an increase in intraoperative fractures in recent literature. Whether the different design of the stems additionally influences the incidence of perioperative local complications, was the goal of this study. METHODS: From January 2008 until June 2010, all patients undergoing primary cementless total hip arthroplasty, using a DMIAA, were consecutively included. The choice of the implant was defined by the day of operation. Age, gender, body mass index, type of prosthesis, and the practical experience of the performing surgeon were retrospectively analyzed. Of main interest were intraoperative fractures, postoperative hematoma, and wound healing. RESULTS: Six hundred forty consecutive patients (64 years [18-94], 339 female, 53%, body mass index 26) have been included. A Quadra-H stem (Medacta) was used in 457 patients (71%). In 183 (29%) patients, a short stem designed for the DMIAA (130 Fitmore, Zimmer and 53 AMIStem, Medacta) was used. We counted 34 (5.3%) intraoperative fractures (16 at the greater trochanter, 18 proximal shaft fractures), 20 (4%) hematomas, and 8 (2%) wound healing problems. The standard length stem showed more local complications (11.8% vs 4.4%) (P = .014, odds ratio 1.63, confidence interval 1.1-2.4) and significantly more (6.8% vs 1.6%) intraoperative fractures (P = .027, odds ratio 1.98, confidence interval 1.1-3.6). CONCLUSION: The standard length stem showed more perioperative complications, especially periprosthetic fractures. It seems that these implants not only put more stress to proximal osseous structures, but there might also be more traction and irritation to the soft tissue while preparing, resulting in more hematomas and wound healing problems. PMID- 28993085 TI - Can Anatomic Measurements of Stem Anteversion Angle Be Considered as the Functional Anteversion Angle? AB - BACKGROUND: Stem anteversion angle is important in the combined anteversion theory to avoid implant impingement after total hip arthroplasty (THA). However, anatomic measurements of stem anteversion angle may not represent functional anteversion of the femur if the femur undergoes axial rotation. Herein, the femoral rotational angle (FRA) was measured in supine and standing positions before and after THA to evaluate the difference between anatomic and functional measurements. METHODS: A total of 191 hips (174 patients) treated with THA for osteoarthritis were analyzed in this retrospective, case-controlled study. The FRA was measured as the angle between the posterior condylar line and the line through the bilateral anterior superior iliac spines (positive for external rotation) and was measured preoperatively and postoperatively in supine and standing positions with computed tomography segmentation and landmark localization of the pelvis and the femur followed by intensity-based 2D-3D registration. The number of cases in which the absolute FRA remained <15 degrees in both positions was also calculated. RESULTS: The average +/- standard deviation preoperative FRA was 0.3 degrees +/- 8.3 degrees in the supine position and -4.5 degrees +/- 8.8 degrees during standing; the postoperative FRA was -3.8 degrees +/- 9.0 degrees in supine and -14.3 degrees +/- 8.3 degrees during standing. There were 134 cases (70%) in which the preoperative absolute FRA remained <15 degrees in both positions while only 85 hips (45%) remained <15 degrees , postoperatively. CONCLUSION: Substantial variability was seen in the FRA, especially during the postoperative period. These results suggest that the anatomic stem anteversion angle may not represent the functional anteversion of the femur. PMID- 28993086 TI - Chronological Changes in Axial Alignment of the Ipsilateral Hip and Knee After Total Hip Arthroplasty. AB - BACKGROUND: Internal rotation of the hip and lateral patellar tilt increases after total hip arthroplasty (THA). However, it remains unknown whether these parameters change with time after the index THA. METHODS: A total of 91 patients undergoing 2-stage bilateral primary THAs between January 2008 and May 2014 were included to assess the association of chronological changes in internal rotation of the hip or lateral patellar tilt with anthropometric and perioperative parameter and changes in alignment after the index THA. Chronological changes were assessed as changes between postoperative computed tomography on the index surgery and the preoperative computed tomography on the contralateral THA. Internal rotation of the hip was defined as the angle between the posterior intercondylar line and a line passing through the posterior inferior iliac spines. Lateral patellar tilt was defined as the angle between the posterior intercondylar line and a line joining the medial and lateral edges of the patella. RESULTS: Internal rotation of the hip and lateral patellar tilt changed until 2 years after the index surgery by a mean of -2 degrees (range -17.3 degrees to 17.7 degrees ) and -2 degrees (range -18.2 degrees to 5.3 degrees ), respectively. Adductor tenotomy was associated with increasing internal rotation of the hip with time (adjusted R2 0.076); leg lengthening and larger preoperative femorotibial angle were associated with decreasing lateral patellar tilt with time (adjusted R2 0.159). CONCLUSION: Both internal rotation of the hip at rest and lateral patellar tilt decreased by approximately 2 degrees until 2 years after surgery and there was a large variation in chronological change. PMID- 28993087 TI - The Influence of Patient Gender on Morbidity Following Total Hip or Total Knee Arthroplasty. AB - BACKGROUND: Little research has focused on the influence of gender on postoperative morbidity following total hip arthroplasty (THA) and total knee arthroplasty (TKA). This study aimed to compare operative time, length of stay, 30-day complications, and readmissions based on patient gender. METHODS: The prospectively collected National Surgical Quality Improvement Program registry from 2005 to 2014 was queried to identify primary elective THA and TKA patients. Multivariate regression was used to compare the rates of 30-day adverse events, rates of readmission, operative time, and postoperative length of stay between men and women. Multivariate analyses were controlled for baseline patient characteristics and procedure type. RESULTS: A total of 173,777 patients were included (63.5% TKA and 36.5% THA). Male gender increased the risk of multiple adverse events, including death (relative risk [RR] 1.1, P < .001), surgical site infection (RR 1.2, P < .001), sepsis (RR 1.4, P < .001), cardiac arrest (RR 1.8, P < .001), and return to the operating room (RR 1.3, P < .001). Men had decreased overall adverse events (RR 0.8, P < .001) secondary to a lower risk of urinary tract infection (RR 0.5, P < .001) and blood transfusion (RR 0.7, P < .001), which were prevalent adverse events. Men had an increased risk of 30-day readmission (RR 1.2, P < .001), slightly increased operative time (+6 minutes, P < .001), and slightly decreased length of stay (-0.2 days, P < .001). CONCLUSION: Men had increased risk of multiple individual adverse events including death, surgical site infection, cardiac arrest, return to the operating room, and readmission. Conversely, women had increased risk of urinary tract infection and blood transfusion. PMID- 28993088 TI - Hip and Knee Arthroplasty Orthopedic Literature in Medical Journals-Is It Negatively Biased? AB - BACKGROUND: Healthcare policy is often determined by well-designed studies most often published in high-impact medical journals. However, concern about the presence of publication bias against lower-extremity arthroplasty-related studies has called into question some of the validity of certain reports. There are only a few studies investigating the presence of the bias in high-impact medical journals against lower-extremity arthroplasty intervention, particularly in the Journal of American Medical Association (JAMA), New England Journal of Medicine (NEJM), and the Lancet. Thus, the purpose of this study was to assess (1) the distribution of positive, neutral, and negative results; (2) the number of reports focused on lower-extremity arthroplasty complications among these 3 journals; and (3) difference in bias between 2 time periods (1975 to 1990 and 2000 to 2016). METHODS: A review of the literature from 3 major medical journals (NEJM, Lancet, and JAMA) was performed using PubMed electronic databases, which retrieved articles between January 1976 and December 2016. Studies were categorized as being positive, neutral, and negatively biased by 2 reviewers. Studies were categorized as reporting on lower-extremity arthroplasty-related complications if they were based on complications including deep vein thrombosis, infection, metal-related complication, fat embolism, readmission, or mortality. In addition, we have compared the journal bias between 2 different time points (1975 to 1990 and 2000 to 2016). Descriptive analyses were performed to assess frequencies. Chi-squared analysis was conducted for categorical variables, whereas a z-test was performed for dichotomous data. RESULTS: When assessing all 3 journals, there were 46 positive (30.3%), 46 negative (30.3%), and 60 neutral reports (39.5%). There was no statistically significant difference in classification proportions between the 3 groups (P = .905). There was a higher percentage of medical literature reporting on the complications of arthroplasty (55.9%); however, this was not statistically significant (z-score = 1.38; 95% confidence interval, 0.48-0.64; P = .17). There was no difference in overall journal reporting between 1975 to 1990 and 2000 to 2016 (P = .548). CONCLUSION: There was no evidence of publication bias of lower-extremity arthroplasty reports in the major medical journals (JAMA, NEJM, and Lancet). However, there were more published studies reporting on complications of lower-extremity arthroplasty. This may be due to systematic bias among journal editors in these journals, or due to low journal submission reporting noncomplications after arthroplasty intervention. We did not find the time period to be a factor in bias reporting of orthopedic literature in major medical journals. More work is needed to verify the results of this study. PMID- 28993089 TI - A two-cohort feasibility study on polyglycolic acid yarn implantation for abolition of saphenous vein reflux. AB - OBJECTIVE: The objective of this study was to evaluate the feasibility and safety of a polyglycolic acid (PGA) yarn implant for nonthermal ablation of saphenous vein reflux. METHODS: In two consecutive cohort studies (TAHOE I and TAHOE II), the feasibility of abolition of great saphenous vein (GSV) reflux by implantation of a PGA yarn was tested under ultrasound guidance in 51 and 30 patients, respectively. The use of tumescent local anesthesia was not required. Graduated compression stockings and thrombosis prophylaxis with low-molecular-weight heparin were used for 2 weeks after intervention in the first study only. RESULTS: Of 81 enrolled patients, 77 (95%) were available at 6-month follow-up. Complete occlusion of the treated GSV was confirmed by duplex ultrasound in all patients except one patient at day 1. In TAHOE II, closure was preserved in a higher percentage of patients at 6 weeks, with 96.4% vs 82.0% in TAHOE I. The 6 month Kaplan-Meier estimated occlusion rates for TAHOE I and TAHOE II were 68% (95% confidence interval [CI], 54%-79%) and 69% (95% CI, 49%-82%), respectively, with an estimated combined occlusion rate of 69% (95% CI, 57%-76%). Kaplan-Meier analysis yielded a combined reflux-free rate of 85% (95% CI, 75%-91%) at 3 months of follow-up and a rate of 81% (95% CI, 71%-88%) at 6 months of follow-up. Venous Clinical Severity Score (VCSS) improved from a combined mean of 4.6 +/- 3.1 at baseline to 2.1 +/- 2.2 and 1.6 +/- 1.9 at 3 and 6 months, respectively (P < .0001 for 3- and 6-month results). In TAHOE II, four patients with venous ulcers healed at an average of 1.3 months after treatment. CONCLUSIONS: First-in-human use of an endovenous PGA yarn implant for occlusion of refluxing GSVs proved to be feasible, with no serious adverse events. However, recanalization was observed during a period of 6 months in 31% of patients. PMID- 28993090 TI - Possible role of rivaroxaban in attenuating pressure-overload-induced atrial fibrosis and fibrillation. AB - BACKGROUND: Coagulation factor Xa (FXa) promotes thrombus formation and exacerbates inflammation via activation of protease-activated receptor (PAR)-2. We tested the hypothesis of whether administration of direct oral anticoagulant, rivaroxaban, would attenuate transverse aortic constriction (TAC)-induced atrial inflammatory fibrosis and vulnerability to atrial fibrillation (AF) in mice. METHODS: Ten-week-old male CL57/B6 mice were divided into a sham-operation (CNT) group and TAC-surgery group. These two groups were then subdivided into vehicle (VEH) and rivaroxaban (RVX) treatment (30MUg/g/day) groups. We assessed PAR-2 expression in response to TAC-related stimulation using rat cultured cells. RESULTS: TAC-induced left atrial thrombus formation was not observed in the TAC RVX group. Cardiac PAR-2 upregulation was observed in both TAC groups. In the quantitative analysis of mRNA levels, cardiac PAR-2 upregulation was attenuated in the TAC-RVX group compared to TAC-VEH group. In histological evaluation, the TAC-VEH group showed cardiac inhomogeneous interstitial fibrosis and abundant infiltration of macrophages, which were attenuated by RVX administration. Electrophysiological examination revealed that AF duration in the TAC group was shortened by RVX administration. TAC-induced protein overexpression of monocyte chemoattractant protein-1, and mRNA overexpression of tumor necrosis factor alpha, interleukin (IL)-1beta and IL-6 in the left atrium was suppressed by RVX treatment. In cardiac fibroblasts, persistent intermittent stretch upregulated PAR-2, which was suppressed by RVX pre-incubation. CONCLUSIONS: These observations demonstrate that coagulation FXa inhibitor probably has a cardioprotective effect against pressure-overload-induced atrial remodeling. PMID- 28993091 TI - Socio-economics perspectives of healthcare in sleep apnea. PMID- 28993092 TI - Raman spectroscopy reveals the lipid phase transition in preimplantation mouse embryos during freezing. AB - Although lipid phase transition is believed to be among the major damaging factors in oocytes and preimplantation embryos cryopreservation, lack of the appropriate experimental methods limits investigation of this phenomenon. Herein, we demonstrate the capabilities of Raman spectroscopy to detect the lipid phase transition within the freezing preimplantation mouse embryos. We exploit the sensibility of antisymmetric CH2 Raman peak to the phase state of lipids. It is shown that during the freezing of the mouse embryos the lipid phase transition occurs at the temperatures between -7 and 0 degrees C. Similar temperature dependences of CH2 mode intensities are found for lipids in the preimplantation embryos and a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, implying the similarity in the occupation rules of conformational states. Raman spectroscopy is considered as a method of choice to study the lipid phase transition during preimplantation mammalian embryos freezing and cryopreservation. PMID- 28993093 TI - Hypersexual Disorder According to the Hypersexual Disorder Screening Inventory in Help-Seeking Swedish Men and Women With Self-Identified Hypersexual Behavior. AB - INTRODUCTION: The Hypersexual Disorder Screening Inventory (HDSI) was developed by the American Psychiatric Association for clinical screening of hypersexual disorder (HD). AIMS: To examine the distribution of the proposed diagnostic entity HD according to the HDSI in a sample of men and women seeking help for problematic hypersexuality and evaluate some psychometric properties. METHODS: Data on sociodemographics, the HDSI, the Sexual Compulsivity Scale (SCS), and the Cognitive and Behavioral Outcomes of Sexual Behavior were collected online from 16 women and 64 men who self-identified as hypersexual. Respondents were recruited by advertisements offering psychological treatment for hypersexual behavior. MAIN OUTCOME MEASURES: The HDSI, covering the proposed criteria for HD. RESULTS: Of the entire sample, 50% fulfilled the criteria for HD. Compared with men, women scored higher on the HDSI, engaged more often in risky sexual behavior, and worried more about physical injuries and pain. Men primarily used pornography, whereas women had sexual encounters. The HD group reported a larger number of sexual specifiers, higher scores on the SCS, more negative effects of sexual behavior, and more concerns about consequences compared with the non-HD group. Sociodemographics had no influence on HD. The HDSI's core diagnostic criteria showed high internal reliability for men (alpha = 0.80) and women (alpha = 0.81). A moderate correlation between the HDSI and the SCS was found (0.51). The vast majority of the entire sample (76 of 80, 95%) fulfilled the criteria for sexual compulsivity according to the SCS. CONCLUSION: The HDSI could be used as a screening tool for HD, although further explorations of the empirical implications regarding criteria are needed, as are refinements of cutoff scores and specific sexual behaviors. Hypersexual problematic behavior causes distress and impairment and, although not included in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, HD should be endorsed as a diagnosis to develop evidence-based treatment and future studies on its etiology. Oberg KG, Hallberg J, Kaldo V, et al. Hypersexual Disorder According to the Hypersexual Disorder Screening Inventory in Help-Seeking Swedish Men and Women With Self Identified Hypersexual Behavior. Sex Med 2017;5:e229-e236. PMID- 28993094 TI - Characterization of diplopia in non-demented patients with Parkinson's disease. AB - INTRODUCTION: Although diplopia is considered a frequent symptom of Parkinson's disease (PD), little is known about its clinical manifestation, associated mechanisms and treatment. Here we characterized binocular diplopia in non demented PD patients in an interdisciplinary setting. METHODS: PD patients were prospectively screened for diplopia, visual hallucinations, problems with spatial perception, contrast sensitivity, presence of blurred vision, and history of ophthalmological comorbidities via interview. Two groups of PD patients, one with and one without diplopia, underwent clinical and ophthalmological assessment to characterize diplopia in these patients. Clinical features were investigated using the Unified Parkinson's Disease Rating Scale and the Non-Motor Symptoms Scale. RESULTS: The frequency of binocular diplopia was 29.6% (n = 37) in our cohort of 125 Parkinson's disease patients. Related mechanisms were heterogeneous including convergence insufficiency, strabismus, and motor fluctuations, as well as symptoms related to visual hallucinations. Diplopia was associated with other visual disturbances like visual hallucinations, blurred vision and problems with spatial perception. Beyond that, diplopia was found to be a predictive factor (3.2, odds ratio) for the occurrence of visual hallucinations in PD. CONCLUSION: Binocular diplopia represents a frequent and relevant symptom in PD patients. Different subtypes should be considered due to different associated mechanisms including ophthalmic pathology and motor fluctuation, as well as intermediate to higher level visual processes. Diplopia seems to be part of a continuous spectrum of positive visual symptoms in Parkinson's disease. PMID- 28993095 TI - Comparison of the brainstem auditory evoked responses during sevoflurane or alfaxalone anaesthesia in adult cats. AB - OBJECTIVE: To compare the effects of general anaesthesia using sevoflurane or alfaxalone on the brainstem auditory evoked response (BAER) test in adult healthy cats. STUDY DESIGN: Prospective, clinical, 'blinded', crossover study. ANIMALS: Ten feral adult healthy cats. METHODS: Premedication consisted of dexmedetomidine (0.01 mg kg-1) intramuscularly (IM). The first general anaesthesia was induced and maintained with sevoflurane (treatment S) for physical examination, BAER test, complete blood tests, thoracic radiographs and abdominal ultrasound. The second general anaesthesia was induced with alfaxalone (treatment A) IM (2 mg kg 1) and maintained with alfaxalone (10 mg kg-1 hour-1) for the BAER test, followed by neutering surgery. The BAER recordings were compared for differences in latencies, amplitudes and waveform morphology. Data were analysed using Student's t test and Wilcoxon rank test for paired samples for parametric and non parametric data, respectively. Statistical significance was set at p < 0.05. RESULTS: General anaesthesia was uneventful; normal BAER comprising five peaks could be identified in both treatments. Mean +/- SD latencies were 1.05 +/- 0.09, 1.83 +/- 0.11, 2.52 +/- 0.19, 3.43 +/- 0.17 and 4.39 +/- 0.15 ms and 1.03 +/- 0.04, 1.81 +/- 0.73, 2.53 +/- 0.15, 3.37 +/- 0.13 and 4.33 +/- 0.13 ms in treatments S and A, respectively. Median (interquartile range) amplitudes were 2.83 (0.67), 1.27 (0.41), 0.30 (0.40), 1.05 (0.82), 0.61 (0.38) microvolts and 2.84 (1.21), 1.49 (1.18), 0.26 (0.32), 0.91 (0.50) and 0.92 (0.64) microvolts in treatments S and A, respectively. There were no statistically significant differences in mean latencies or median amplitudes between both the anaesthetics. CONCLUSIONS AND CLINICAL RELEVANCE: This study demonstrates that there were no statistically significant differences between both the anaesthetics on the BAER test in adult healthy cats. Moreover, two possible anaesthetic protocols are described for cats undergoing this electrodiagnostic test. PMID- 28993097 TI - Prognostic value of early warning scores in the emergency department (ED) and acute medical unit (AMU): A narrative review. AB - BACKGROUND: A wide array of early warning scores (EWS) have been developed and are used in different settings to detect which patients are at risk of deterioration. The aim of this review is to provide an overview of studies conducted on the value of EWS on predicting intensive care (ICU) admission and mortality in the emergency department (ED) and acute medical unit (AMU). METHODS: A literature search was conducted in the bibliographic databases PubMed and EMBASE, from inception to April 2017. Two reviewers independently screened all potentially relevant titles and abstracts for eligibility. RESULTS: 42 studies were included. 36 studies reported on mortality as an endpoint, 13 reported ICU admission and 9 reported the composite outcome of mortality and ICU admission. For mortality prediction National Early Warning Score (NEWS) was the most accurate score in the general ED population and in those with respiratory distress, Mortality in Emergency Department Sepsis score (MEDS) had the best accuracy in patients with an infection or sepsis. ICU admission was best predicted with NEWS, however in patients with an infection or sepsis Modified Early Warning Score (MEWS) yielded better results for this outcome. CONCLUSION: MEWS and NEWS generally had favourable results in the ED and AMU for all endpoints. Many studies have been performed on ED and AMU populations using heterogeneous prognostic scores. However, future studies should concentrate on a simple and easy to use prognostic score such as NEWS with the aim of introducing this throughout the (pre-hospital and hospital) acute care chain. PMID- 28993096 TI - Altered expression of MALAT1 lncRNA in nonalcoholic steatohepatitis fibrosis regulates CXCL5 in hepatic stellate cells. AB - In the present study, we sought to identify long noncoding RNA (lncRNA) expression profiles in nonalcoholic steatohepatitis (NASH) patients with histologic evidence of lobular inflammation and advanced fibrosis. We profiled lncRNA expression using RNA-sequencing of wedge liver biopsies from 24 nonalcoholic fatty liver disease (NAFLD) patients with normal liver histology, 53 NAFLD patients with lobular inflammation, and 65 NAFLD patients with advanced fibrosis. Transcript profiling identified 4432 and 4057 differentially expressed lncRNAs in comparisons of normal tissue with lobular inflammation and fibrosis samples, respectively. Functional enrichment analysis revealed lncRNA participation in transforming growth factor beta 1 and tumor necrosis factor signaling, insulin resistance, and extracellular matrix maintenance. Several lncRNAs were highly expressed in fibrosis relative to normal tissue, including nuclear paraspeckle assembly transcript 1, hepatocellular carcinoma upregulated lncRNA, and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1). Two potential target mRNAs, syndecan 4 (SDC4), and C-X-C motif chemokine ligand 5 (CXCL5) were identified for hepatocellular carcinoma upregulated lncRNA and MALAT1, respectively, but only CXCL5 showed differential expression among the different histologic classes. Knockdown of MALAT1 expression reduced CXCL5 transcript and protein levels by 50% and 30%, respectively, in HepG2 cells. The expression of MALAT1 and CXCL5 was upregulated in activated hepatic stellate (LX 2) cells compared to cells in the quiescent state, and MALAT1 expression was regulated by hyperglycemia and insulin in HepG2 cells, but only by insulin in LX 2 cells. Dysregulated lncRNA expression is associated with inflammation and fibrosis in NASH. Functionally relevant differences in MALAT1 expression may contribute to the development of fibrosis in NASH through mechanisms involving inflammatory chemokines. PMID- 28993098 TI - Acute Oncology Care: A narrative review of the acute management of neutropenic sepsis and immune-related toxicities of checkpoint inhibitors. AB - Cancer care has become increasingly specialized and advances in therapy have resulted in a larger number of patients receiving care. There has been a significant increase in the number of patients presenting with cancer related emergencies including treatment toxicities and those directly related to the malignancy. Suspected neutropenic sepsis is an acute medical emergency and empirical antibiotic therapy should be administered immediately. The goal of empirical therapy is to cover the most likely pathogens that will cause life threatening infections in neutropenic patients. Patients with febrile neutropenia are a heterogeneous group with only a minority of treated patients developing significant medical complications. Outpatient management of low risk febrile neutropenia patients identified by the MASCC score is a safe and effective strategy. Immunotherapy with "checkpoint inhibitors" has significantly improved outcomes for patients with metastatic melanoma and evidence of benefit in a wide range of malignancies is developing. Despite these clinical benefits a number of immune related adverse events have been recognised which can affect virtually all organ systems and are potentially fatal. The timing of the onset of the adverse events is dependent on the organ system affected and unlike anti-neoplastic therapy can be delayed significantly after initiation or completion of therapy. The field of Acute Oncology is changing rapidly. Alongside, the traditional challenge of neutropenic sepsis there are many emerging toxicities. Further research into the optimal management, strategies and pathways of acutely unwell patients with cancer is required. PMID- 28993099 TI - Recognising older frail patients near the end of life: What next? AB - Frailty is a state of vulnerability resulting from cumulative decline in many physiological systems during a lifetime. It is progressive and considered largely irreversible, but its progression may be controlled and can be slowed down and its precursor -pre-frailty- can be treated with multidisciplinary intervention. The aim of this narrative review is to provide an overview of the different ways of measuring frailty in community settings, hospital, emergency, general practice and residential aged care; suggest occupational groups who can assess frailty in various services; discuss the feasibility of comprehensive geriatric assessments; and summarise current evidence of its management guidelines. We also suggest practical recommendations to recognise frail patients near the end of life, so discussions on goals of care, advance care directives, and shared decision-making including early referrals to palliative and supportive care can take place before an emergency arises. We acknowledge the barriers to systematically assess frailty and the absence of consensus on best instruments for different settings. Nevertheless, given its potential consequences including prolonged suffering, disability and death, we recommend identification of frailty levels should be universally attempted in older people at any health service, to facilitate care coordination, and honest discussions on preferences for advance care with patients and their caregivers. PMID- 28993100 TI - Introduction: Towards a global history of paleontology: The paleontological reception of Darwin's thought. PMID- 28993101 TI - Representations and motivations of blood donation in adolescence through a mixed method approach. AB - BACKGROUND: Scientific literature on blood donation is prevalently concentrated on adults, leaving out adolescents almost completely. While the latter represents "ideal" candidates, they constitute, however, the segment of the population least present among blood donors. OBJECTIVES: The present work, composed of two studies, proposes looking into the representations that the adolescents have of blood donation and give voice to the motivations that could persuade them to becoming donors once they reach the legal age for donation. Study I aims to investigate adolescents' representations about the world of blood donation. Study II aims to investigate a) the underlying motivations for blood donations and b) the relationship between motivations and propensity to donate. MATERIALS/METHODS: This paper is based on a mixed methods research design. In Study I, five focus groups were conducted comprising a total of 25 adolescents; for Study II, a self report questionnaire was administered to 285 adolescents. RESULTS: Study I reveals a lack of information for everything regarding donation, something that produces fear, false beliefs, and an idealized image of the donor. Study II shows that for males, social motivations are fundamental while ego-protective motivations are deterrents, and that females are most impacted by understanding. CONCLUSION: The study shows how the adolescent population cannot be recruited in the same way as adults, and presents valuable points for those who finalize advertising campaigns for donor recruitment recruitment. PMID- 28993102 TI - Examining the role of sex in self-injurious thoughts and behaviors. AB - Self-injurious thoughts and behaviors (SITBs), including nonsuicidal self-injury, suicidal thoughts, suicide attempts, and suicide death exhibit substantial sex differences. Across most countries, men die by suicide more frequently than women; yet, women think about and attempt suicide more frequently than men. Research on sex differences in nonsuicidal self-injury is less developed; however, nonsuicidal self-injury is historically understood as a primarily female phenomenon. This review describes current research on sex differences across SITBs with a focus on factors that moderate these effects, such as age, race, geographic region, and time. Additionally, this review describes factors that may help to explain why sex differences across SITBs exist, including differences in culture, access to lethal suicide methods, rates of mental illness, and utilization of health care. The role of gender, and particularly non-binary gender, is also discussed. Current understanding of these sex differences is described with an eye toward future research on this topic. PMID- 28993103 TI - The long-term effects of bibliotherapy in depression treatment: Systematic review of randomized clinical trials. AB - OBJECTIVE: Literature shows bibliotherapy can be helpful for moderate depression treatment. The aim of this systematic review is to verify the long-term effects of bibliotherapy. METHODS: After bibliographic research, we included RCTs articles about bibliotherapy programme treatment of depression published in English language between 1990 and July 2017. All RCTs were assessed with Cochrane's Risk of Bias tool. RESULTS: Ten articles (reporting 8 studies involving 1347 subjects) out of 306 retrieved results were included. All studies analyze the effects of bibliotherapy after follow-up periods ranging from 3months to 3years and show quiet good quality in methods and analyses. The treatment was compared to standard treatments or no intervention in all studies. After long term period follow-ups, six studies, including adults, reported a decrease of depressive symptoms, while four studies including young people did not show significant results. CONCLUSION: Bibliotherapy appears to be effective in the reduction of adults depressive symptoms in the long-term period, providing an affordable prompt treatment that could reduce further medications. The results of the present review suggest that bibliotherapy could play an important role in the treatment of a serious mental health issue. Further studies should be conducted to strengthen the evidence of bibliotherapy's efficacy. PMID- 28993104 TI - Understanding patient adherence to inhaled medication: The social representations of COPD. PMID- 28993105 TI - Dual trigger of final oocyte maturation in poor ovarian responders undergoing IVF/ICSI cycles. AB - Previous studies show that a dual trigger ovulation regimen significantly improves number and maturity of retrieved oocytes for normal ovarian responders or patients with history of low oocyte yield. The current retrospective cohort study investigated whether dual trigger of final oocyte maturation may benefit IVF outcomes for poor ovarian responders fulfilling the Bologna criteria. Undertaken between May 2014 and August 2016, the study involved 1350 patients undergoing 1389 IVF/intracytoplasmic sperm injection treatment cycles. Patients triggered with 5000 IU human chorionic gonadotrophin (HCG) alone (328 cycles) were compared with those undergoing dual triggering with 5000 IU HCG plus 0.1 mg gonadotrophin-releasing hormone agonist (GnRHa) (386 cycles) and patients triggered with 10,000 IU HCG (363 cycles) were compared with those undergoing dual triggering with 10,000 IU HCG plus 0.1 mg GnRHa (312 cycles). The dual trigger groups showed significantly higher number of oocytes collected and number of mature oocytes compared with their respective HCG trigger group (P < 0.001). Oocyte retrieval rate and percentage of mature oocytes retrieved were also both significantly higher in the dual trigger groups (P < 0.001). Fertilization rate, number of viable embryos, implantation rate, clinical pregnancy rate and miscarriage rate were not significantly different between groups. PMID- 28993107 TI - Diagnostic flaws in oral lichen planus and related lesions. PMID- 28993106 TI - The antitubercular activity of various nitro(triazole/imidazole)-based compounds. AB - Twenty three 3-nitrotriazole- and five nitroimidazole-based compounds, mostly amides, were screened for antitubercular activity against Mycobacterium tuberculosis H37Rv (Mtb H37Rv) under aerobic or low oxygen conditions, intracellular activity in murine J774 macrophages or THP-1 cells, activity against resistant Mtb strains as well as cytotoxicity in normal cells. Compounds with a Minimum Inhibitory Concentration (MIC) less than 10MUM and 10-50MUM were characterized as active and moderately active, respectively, whereas compounds with a MIC >50MUM were characterized inactive. Fifteen 3-nitrotriazole-based compounds were active or moderately active against aerobic Mtb and thirteen of them were bactericidal, however, only four 3-nitrotriazoles were moderately active against anaerobic Mtb. All examined 2-nitroimidazole-based compounds were inactive against aerobic Mtb, and from the ones examined against anaerobic Mtb, only one was found moderately active. All examined compounds demonstrated intracellular activity and lack of cross-resistance. The five active 3 nitrotriazoles demonstrated good selectivity for Mtb. In conclusion, these classes of 3-nitrotriazole-based compounds merit further investigation as potential antitubercular agents. PMID- 28993109 TI - Utilization of Computer-Aided Detection for Digital Screening Mammography in the United States, 2008 to 2016. AB - PURPOSE: Computer-aided detection (CAD) for screening mammography is a software technology designed to improve radiologists' reading performance. Since 2007, multiple Breast Cancer Surveillance Consortium research papers have shown that CAD decreases performance by increasing recalls and decreasing the detection of invasive cancer while increasing the detection of ductal carcinoma in situ. The aim of this study was to test the hypothesis that CAD use by digital mammography facilities would decrease over time. METHODS: In August 2007, August 2011, and March 2016, the FDA database of certified mammography facilities was accessed, and a random sample of 400 of approximately 8,500 total facilities was generated. In 2008 and 2011, a telephone survey was conducted of the facilities regarding digital mammography and CAD use. In 2016, facility websites were reviewed before calling the facilities. Bonferroni-corrected P values were used to assess statistical differences in the proportion of CAD at digital facilities for the three surveys. RESULTS: The mean proportion of digital facilities using CAD was 91.4%, including 91.4% (128 of 140) in 2008, 90.2% (238 of 264) in 2011, and 92.3% (358 of 388) in 2016. The difference for 2008 versus 2011 was 1.3% (95% confidence interval [CI], -0.5% to 7.7%), for 2011 versus 2016 was -2.1% (95% CI, -6.9% to 2.7%), and for 2008 versus 2016 was -0.8% (95% CI, -6.7% to 5.0%). CONCLUSIONS: In three national surveys, it was found that CAD use at US digital screening mammography facilities was stable from 2008 to 2016. This persistent utilization is relevant to the debate on the value of targeting ductal carcinoma in situ in screening. PMID- 28993108 TI - Evaluation of interfractional variation of organs and displacement of catheters during high-dose-rate interstitial brachytherapy for gynecologic malignancies. AB - PURPOSE: To investigate the dosimetric effects due to interfractional changes in catheter position and variation in patient's anatomy during the course of interstitial high-dose-rate (HDR) brachytherapy. METHODS AND MATERIALS: A total of 15 patients with either cervical or vaginal cancer underwent interstitial HDR brachytherapy. Interstitial catheters and fiducials were placed under fluoroscopy and intraoperative 3T MRI to confirm the desired catheter placement for adequate target volume coverage. Single plan was generated from first-fraction CT fused with the MRI and used for all fractions of treatment. CT image was acquired before each treatment and registered to the first-fraction CT. Displacement of fiducials and catheters was calculated for each fraction and its effects on dosimetric parameters such as dose covering 90% for high-risk clinical target volume and intermediate-risk clinical target volume and dose to the 2 cm3 of the volume for bladder, rectum, sigmoid, and bowel were studied. RESULTS: Average movements of fiducials and catheters were 1.6 mm (range: 0.1-7.1 mm) and 1.7 mm (range: 0.1-4.5 mm), respectively. Overall, deviation of the delivered dose to the target in each fraction was insignificant for all patients (p-value: 0.66 for high-risk clinical target volume and 0.87 for intermediate-risk clinical target volume). The mean dose to organs at risk showed maximum difference up to 0.9, 2.7, 1.6, and 2.1 Gy for bladder, rectum, sigmoid, and bowel, respectively (p value: 0.88, 0.34, 0.68, and 0.85 for bladder, rectum, sigmoid, and bowel, respectively). CONCLUSIONS: The interfractional dosimetric variation for both target and organs at risk was within clinically acceptable limit throughout the entire course of interstitial HDR-Syed brachytherapy. Only 6% of cases performed replanning, which could be readily identified using CT imaging. PMID- 28993110 TI - Chlorhexidine gluconate bathing practices and skin concentrations in intensive care unit patients. AB - In this 2-phase real-world evaluation of chlorhexidine gluconate (CHG) skin concentrations in intensive care unit patients, we found lower skin CHG concentrations when rinsing with water after CHG solution bath (compared with no rinse), but no significant difference in concentrations between the use of CHG solution without rinse and preimpregnated CHG wipes. CHG concentration audits could be useful in assessing the quality of bathing practice, and CHG solution without rinsing may be an alternative to preimpregnated CHG wipes. PMID- 28993111 TI - The annular ligament-revisited. AB - BACKGROUND: Studies investigating the annular ligament have presented confusing information about its anatomy and nomenclature. Cadaver elbow dissections were used to clarify the anatomy and terminology of the annular ligament. METHODS: Nineteen elbows were dissected (7 fresh frozen and 12 embalmed). Target structures were identified, photographed, and measured by independent observers. RESULTS: There are 3 layers to the lateral elbow ligaments: the superficial lateral ulnar collateral and radial collateral ligament; a deeper layer of the superior oblique band (SOB) and inferior oblique band (IOB) of the annular ligament; and the deepest capsular layer. The annular ligament measured 9.5 +/- 1.4 mm anteriorly. The SOB (15/19) was 3.9 +/- 1.0 mm wide by 10.5 +/- 3.8 mm long. The IOB (13/19) was 3.6 +/- 1.1 mm wide by 11.4 +/- 4.2 mm long. The IOB inserts onto the anterior proximal ulna rather than the supinator crest. The anterior oblique band (8/19) was 3.8 +/- 1.7 mm wide. CONCLUSION: The SOB and IOB were present in the majority of specimens. The previously described accessory lateral collateral ligament is a localized thickening on the lateral ligament complex arising from the supinator insertion independent of the IOB that attaches to the annular ligament inferiorly and distally and attaches onto the proximal anterior ulna at the bicipital fossa floor, medial to the supinator crest. PMID- 28993112 TI - Hospitalization due to acute exacerbation of chronic pain: An intervention study in a university hospital. AB - BACKGROUND AND AIMS: Hospitalization as a result of acute exacerbation of complex chronic pain is a largely hidden problem, as patients are often admitted to hospital under a variety of specialities, and there is frequently no overarching inpatient chronic pain service dedicated to their management. Our institution had established an inpatient acute pain service overseen by pain physicians and staffed by specialist nurses that was intended to focus on the management of perioperative pain. We soon observed an increasing number of nurse-to-nurse referrals of non-surgical inpatients admitted with chronic pain. Some of these patients had seemingly intractable and highly complex pain problems, and consequently we initiated twice-weekly attending physician-led inpatient pain rounds to coordinate their management. From these referrals, we identified a cohort of 20 patients who were frequently hospitalized for long periods with exacerbations of chronic pain. We sought to establish whether the introduction of the physician-led inpatient pain ward round reduced the number and duration of hospitalizations, and costs of treatment. METHODS: We undertook a retrospective, observational, intervention cohort study. We recorded acute Emergency Department (ED) attendances, hospital admissions, and duration and costs of hospitalization of the cohort of 20 patients in the year before and year after introduction of the inpatient pain service. RESULTS: The patients' mean age was 38.2 years (+/ standard deviation 13.8 years, range 18-68 years); 13 were women (65.0%). The mode number of ED attendances was 4 (range 2-15) pre-intervention, and 3 (range 0 9) afterwards (p=0.116). The mode bed occupancy was 32 days (range 9-170 days) pre-intervention and 19 days (range 0-115 days) afterwards (p=0.215). The total cost of treating the cohort over the 2-year study period was L733,010 (US$1.12m), comprising L429,479 (US$656,291) of bed costs and L303,531 (US$463,828) of investigation costs. The intervention did not achieve significant improvements in the total costs, bed costs or investigation costs. CONCLUSIONS: Despite our attending physician-led intervention, the frequency, duration and very substantial costs of hospitalization of the cohort were not significantly reduced, suggesting that other strategies need to be identified to help these complex and vulnerable patients. IMPLICATIONS: Frequent hospitalization with acute exacerbation of chronic pain is a largely hidden problem that has very substantial implications for patients, their carers and healthcare providers. Chronic pain services tend to focus on outpatient management. Breaking the cycle of frequent and recurrent hospitalization using multidisciplinary chronic pain management techniques has the potential to improve patients' quality of life and reduce hospital costs. Nonetheless, the complexity of these patients' chronic pain problems should not be underestimated and in some cases are very challenging to treat. PMID- 28993114 TI - Reflections on research competence in Family and Community Nursing. PMID- 28993113 TI - The cognitive impact of chronic low back pain: Positive effect of multidisciplinary pain therapy. AB - OBJECTIVES: Little is known about the affected cognitive problems in chronic low back pain patients. For this patient cohort research mostly focused on memory of pain, rather than cognitive difficulties related to pain. Chronic pain may be associated with specific (yet undefined) cognitive deficits that affect everyday behaviour. We set out to compare the cognitive function of patients with chronic low back pain (cLBP) in the course of multidisciplinary pain treatments before and after therapy. METHODS: Thirty-three patients with cLBP and 25 healthy controls between 20 and 70 years were recruited into the study. The inclusion criteria for patients were: (1) a history of at least 12 weeks of chronic myofascial low back pain without radicular pain sensation before enrolment; (2) grade II and higher chronicity according to von Korff; (3) no opioid medication. The patients recruited had a mean pain duration of 7.13+/-7.16 years and reported a mean pain intensity of 6.62+/-2.04 (visual analogue score, VAS). Their mean back function according to the Funktionsfragebogen Hannover (FFbH, a questionnaire comparable with the Health Assessment Questionnaire) was 52.39+/ 20.23%. At three time points (before therapy, 3 weeks and 6 months after therapy) the study subjects were assessed prospectively with a battery of visual memory tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB). These included choice reaction time (CRT), pattern recognition memory (PRM) and spatial span (SSP). In parallel, the Trail-Making Test (TMT-A, TMT-B) and the Wechsler Adult Intelligence Scale (WAIS-III) were used to evaluate intelligence and cognitive flexibility. RESULTS: At the beginning of MDPT (T1), it took patients with cLBP significantly longer than HC to complete TMT-A (38.29+/-19.99s vs 30.25+/-14.19s, p=0.047) and TMT-B (72.10+/-26.98s vs 55.99+/-22.14s, p=0.034). There were no significant differences between patients and HC in CRT, PRM and SSP. Three weeks (T2) and 6 months (T3) after MDPT, TMT-A reaction time of patients significantly improved by 6.5s and 8.1ms (38.3 +/-19.9s vs 31.8+/ 12.3s, p=0.02 and 31.8+/-12.3s vs 30.2+/-8.9s, p=0.021, respectively). The patients' working memory was also better 6 months after MDPT (48.8+/-11.1% at T1, 51.2+/-11.9% at T2, 57.1+/-10.9% at T3, p=0.008). Significant correlations among pain, depression/anxiety, medication and neuropsychological tests were found. CONCLUSIONS: These findings show that patients with cLBP have slowed speeds of information processing and working memory, but no alteration in attention and recognition memory. There are clearly interactions of cognitive function with pain, depression, anxiety, and medication. MDPT may improve the impaired cognitive function of patients with cLBP. IMPLICATION: Health professionals should contemplate the results from this study when planning therapy strategies especially when prescribing pain medications such opioids to patients with chronic low back pain. PMID- 28993115 TI - Recurrent exposure to ferric oxide nanoparticles alters myocardial oxidative stress, apoptosis and necrotic markers in male mice. AB - The cardiotoxicity of iron oxide nanoparticles (Fe2O3-NPs) in mice was investigated. The mice were intraperitoneally administered with Fe2O3-NPs at the dose of 25 and 50 mg/kg bw for 30 days at seven days interval. In vivo MRI analysis reveals the Fe2O3-NPs accumulation in the cardiac system. Also, serum iron estimation and Prussian blue staining confirms the iron deposition in circulatory system. Cardiac dysfunction was assessed by ECG analysis and further validated by evaluating the functional markers such as cardiac Troponin-1 (cTnI) expression, AChE activity and levels of LDH and CK-MB in cardiac tissue. Fe2O3 NPs exposure disturbs the balance between the oxidants and antioxidants resulting in oxidative myocardial damages. In consequence, damaged mitochondria, diminished ATP level and NOX4 over expression were observed in the intoxicated groups indicating the role of Fe2O3-NPs in oxidative stress. A dose dependant increase in oxidative stress mediates apoptosis through upregulation of Bax, cytochrome c and cleaved caspase 3 in the 25 mg/kg treated group. Sustained oxidative stress suggest the occurrence of necrosis in addition to apoptosis in 50 mg/kg treated group evidenced by altered expression pattern of cleaved PARP, cytochrome c, Bax and cleaved caspase 3. In addition, triphenyl tetrazolium chloride (TTC) staining confirms cardiac necrosis in 50 mg/kg Fe2O3-NPs treated group. PMID- 28993116 TI - Right Ventricular Epicardial Vascularisation in Patients With Pulmonary Arterial Hypertension. AB - BACKGROUND: Pulmonary arterial hypertension (PAH) leads to a haemodynamic overload and ischaemia of the right ventricle (RV), which are important triggers of an arterial growth. Thus, we aimed to assess whether patients with PAH have altered epicardial vasculature of the RV, and how it corresponds to RV haemodynamic stress. METHODS: We enrolled consecutive patients with PAH diagnosed in a single pulmonary hypertension centre, who underwent coronary angiography. The control group consisted of patients with normal coronary arteries. Artery branches from segments I-III of the right coronary artery (RCAB) and branches of the left coronary artery (LCAB) were assessed. The sum of the diameters of RCABs (RCAB_sum) was used as a marker of RV epicardial vascularisation. Linear regression models were used to investigate associations between the RCAB_sum and markers of RV dysfunction. RESULTS: We recruited 37 PAH patients (idiopathic, n=25; associated with connective tissue disease, n=12) and 37 control subjects of similar age (56+/-18 vs. 56+/-13 years, p=0.99) and sex (73% vs. 73% of women, p=0.99). Pulmonary arterial hypertension patients as compared with control subjects had more RCABs (7 [6-8] vs. 6 [5-7], p<0.001) and increased RCAB_sum (9.4 [8.2-10.5] vs. 7.3 [6.6-7.40] mm; p<0.001) although comparable LCAB count (4 [4-5] vs. 4 [4-5]; p=0.50). In a stepwise multivariable linear regression model, RA area (beta=0.152 [0.062-0.242]; p=0.002) and diastolic wall stress (beta=0.025 [0.005-0.045]; p=0.02) were significant predictors of RCAB_sum (model R2=0.65; p<0.0001). CONCLUSIONS: Right ventricular epicardial vasculature is more extensive in PAH patients as compared with control subjects, and it is in linear relation to potential markers of RV diastolic dysfunction. PMID- 28993117 TI - Getting to the Heart of the Matter: What is the Landscape of Exercise Rehabilitation for People With Heart Failure in Australia? AB - BACKGROUND: The benefits of exercise rehabilitation for people with heart failure (HF) are well established. In Australia, little is known about how the guidelines around exercise rehabilitation for people with HF are being implemented in clinical practice. Furthermore, it is unknown what organisational barriers are faced in providing exercise rehabilitation programs for this population. The aim of this study is to provide an updated review of exercise rehabilitation services for people with HF in Australia and to identify perceived organisational barriers to providing these services. METHODS: A cross-sectional survey of cardiac rehabilitation centres in Australia, investigating the number and characteristics of services providing exercise rehabilitation for people with HF. RESULTS: A total of 334 of 457 identified services responded to the survey. Of these, 251 reported providing a supervised group-based exercise rehabilitation program for people with HF. These services were mapped, showing their distribution across Australia. Services which were unable to provide group-based exercise training for HF patients reported organisational barriers including insufficient funding (60%), staffing (56%) and clinical resources (53%). Of the 78 services that reported patients in their local area were unable to access appropriate exercise guidance, 81% were located in regional or remote areas. We found that reported exercise practices align with current best-practice guidelines with 99% of group based exercise programs reportedly including endurance training and 89% including resistance training. CONCLUSIONS: In Australia, exercise practices for people with HF align with current best-practice guidelines for this condition. Limited resources, funding and geographic isolation are reported as the major organisational barriers to providing these programs. Future endeavours should include the development of alternative and flexible delivery models such as telerehabilitation and other home-based therapies to improve access for these individuals to such services. PMID- 28993118 TI - Th17/Treg Ratio in Serum Predicts Onset of Postoperative Atrial Fibrillation After Off-Pump Coronary Artery Bypass Graft Surgery. AB - BACKGROUND: The aim of this study is to identify whether the balance between T helper 17 (Th17) cells and CD4+CD25+Foxp3+ regulatory T (Treg) cells could predict the postoperative atrial fibrillation (POAF) after coronary artery bypass graft surgery (CABG). METHODS: We enrolled 88 patients from Xinhua Hospital who received off-pump CABG (OPCABG) surgery. The baseline characteristics of patients were recorded. The preoperative variables C-reactive protein (CRP) level, left atrial (LA) volume, EuroSCORE I score, CHADS2 score, and CHA2DS2-VASc score were calculated at enrolment. Circulating Th17 and Treg cell frequencies were determined by flow cytometry, and expressions of Th17- and Treg-related cytokines were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared to patients without POAF, the CRP level and peripheral circulating Th17 cell were significantly increased in POAF patients. Th17/Treg ratio was positively correlated with CRP level, LA volume, CHADS2 score, and CHA2DS2-VASc score. The areas under the receiver-operating characteristic (AUC) curves of Th17/Treg ratio for predicting POAF occurrence was higher than that of CRP level, LA volume, CHADS2 score and CHA2DS2-VASc score. Th17/Treg ratio combined with CRP level has the highest AUC and a greater balance between sensitivity and specificity for predicting POAF. CONCLUSIONS: Our data suggest that a Th17/Treg imbalance due to a Th17 shift, representing a pro-inflammatory tendency, participates in the development of POAF. Combining the Th17/Treg ratio with CRP level may provide a more accurate, sensitive, and specific indicator for prediction of POAF. PMID- 28993119 TI - Plant Phospholipid Diversity: Emerging Functions in Metabolism and Protein-Lipid Interactions. AB - Phospholipids are essential components of biological membranes and signal transduction cascades in plants. In recent years, plant phospholipid research was greatly advanced by the characterization of numerous mutants affected in phospholipid biosynthesis and the discovery of a number of functionally important phospholipid-binding proteins. It is now accepted that most phospholipids to some extent have regulatory functions, including those that serve as constituents of biological membranes. Phospholipids are more than an inert end product of lipid biosynthesis. This review article summarizes recent advances on phospholipid biosynthesis with a particular focus on polar head group synthesis, followed by a short overview on protein-phospholipid interactions as an emerging regulatory mechanism of phospholipid function in arabidopsis (Arabidopsis thaliana). PMID- 28993120 TI - Coronary lumen volume to myocardial mass ratio in primary microvascular angina. AB - BACKGROUND: Microvascular angina (MVA) is an incompletely understood clinical entity. Computational analysis of coronary Computed Tomography Angiography (CTA) has shown an association between low coronary lumen volume to myocardial mass (V/M) ratio and lower Fractional Flow Reserve values, independent of plaque measures. We hypothesized that low V/M ratio may be present in patients with MVA. METHODS: A retrospective case-control analysis was performed using patients fulfilling guideline criteria for MVA with controls matched for age, gender, coronary risk factors and atherosclerotic plaque burden. V/M was extracted off site (Heartflow Inc; Redwood City, CA) employing allometric scaling laws that allow the definition of the coronary circulation beyond the epicardium. FFRCT values were calculated in the major epicardial coronary arteries for each group. RESULTS: A total of 30 patients with MVA and 32 matched controls were included in the study. Mean total coronary lumen volume (2302 mm3 +/- 109 vs 2978 mm3 +/- 134, p < 0.001) and mean myocardial mass (90.4 g +/- 13.7 vs 100.4 g +/- 20.1, p = 0.029) were lower in MVA patients compared to controls. Mean V/M ratio was significantly lower in MVA compared to controls (25.6 mm3/g +/- 5.9 vs 30.0 mm3/g +/- 6.5, p = 0.007; c-statistic 0.69). V/M ratio did not differ significantly between subclasses of angina severity (p = 0.747). No difference in mean nadir FFRCT values was found between MVA and control groups in the LAD (0.86 +/- 0.07 vs 0.83 +/- 0.07, p = 0.154), LCX (0.90 +/- 0.05 vs 0.90 +/- 0.06, p = 0.240) and RCA (0.90 +/- 0.04 vs 0.90 +/- 0.03, p = 0.773) vessels. CONCLUSION: Patients with microvascular angina demonstrate a significantly lower coronary CTA-derived coronary volume/myocardial mass ratio than asymptomatic controls. PMID- 28993121 TI - Evaluating Surgical Residents' Patient-Centered Communication Skills: Practical Alternatives to the "Apprenticeship Model". AB - OBJECTIVES: The Accreditation Council for Graduate Medical Education (ACGME) requires residency programs to assess communication skills and provide feedback to residents. We aimed to develop a feasible data collection process that generates objective clinical performance information to guide training activities, inform ACGME milestone evaluations, and validate assessment instruments. DESIGN: Residents care for patients in the surgical clinic and in the hospital, and participate in a communication curriculum providing practice with standardized patients (SPs). We measured perception of resident communication using the 14-item Communication Assessment Tool (CAT), collecting data from patients at the surgery clinic and surgical wards in the hospital, and from SP encounters during simulated training scenarios. We developed a handout of CAT example behaviors to guide patients completing the communication assessment. SETTING: Independent academic medical center. PARTICIPANTS: General surgery residents. RESULTS: The primary outcome is the percentage of total items patients rated "excellent;" we collected data on 24 of 25 residents. Outpatient evaluations resulted in significantly higher scores (mean 84.5% vs. 68.6%, p < 0.001), and female patients provided nearly statistically significantly higher ratings (mean 85.2% vs. 76.7%, p = 0.084). In multivariate analysis, after controlling for patient gender, visit reason, and race, (1) residents' CAT scores from SPs in simulation were independently associated with communication assessments in their concurrent patient population (p = 0.017), and (2) receiving CAT example instructions was associated with a lower percentage of excellent ratings by 9.3% (p = 0.047). CONCLUSIONS: Our data collection process provides a model for obtaining meaningful information about resident communication proficiency. CAT evaluations of surgical residents by the inpatient population had not previously been described in the literature; our results provide important insight into relationships between the evaluations provided by inpatients, clinic patients, and SPs in simulation. Our example behaviors guide shows promise for addressing a common concern, minimizing ceiling effects when measuring physician-patient communication. PMID- 28993122 TI - Characterization of novel monoclonal antibodies against the MERS-coronavirus spike protein and their application in species-independent antibody detection by competitive ELISA. AB - Since discovering the Middle East respiratory syndrome coronavirus (MERS-CoV) as a causative agent of severe respiratory illness in the Middle East in 2012, serological testing has been conducted to assess antibody responses in patients and to investigate the zoonotic reservoir of the virus. Although the virus neutralization test is the gold standard assay for MERS diagnosis and for investigating the zoonotic reservoir, it uses live virus and so must be performed in high containment laboratories. Competitive ELISA (cELISA), in which a labeled monoclonal antibody (MAb) competes with test serum antibodies for target epitopes, may be a suitable alternative because it detects antibodies in a species-independent manner. In this study, novel MAbs against the spike protein of MERS-CoV were produced and characterized. One of these MAbs was used to develop a cELISA. The cELISA detected MERS-CoV-specific antibodies in sera from MERS-CoV-infected rats and rabbits immunized with the spike protein of MERS-CoV. The MAb-based cELISA was validated using sera from Ethiopian dromedary camels. Relative to the neutralization test, the cELISA detected MERS-CoV-specific antibodies in 66 Ethiopian dromedary camels with a sensitivity and specificity of 98% and 100%, respectively. The cELISA and neutralization test results correlated well (Pearson's correlation coefficients=0.71-0.76, depending on the cELISA serum dilution). This cELISA may be useful for MERS epidemiological investigations on MERS-CoV infection. PMID- 28993123 TI - Single mutation in the matrix gene of seasonal influenza A viruses critically affects the performance of diagnostic molecular assay. AB - Reduced intensity of the fluorescence signal in the amplification curve was observed when using a WHO recommended real time RT-PCR for influenza virus detection. A single mutation, G189T, in the conserved region of influenza virus matrix gene was detected by Sanger sequencing. The mutation is located in the probe binding region, hence we speculated it could be the reason for the atypical shape of amplification curve. The mutation was first noted in Slovenia in 2011 and 2013 for seasonal influenza A virus types A(H1N1)pdm09 and A(H3N2), respectively. In the following years, 2014 and 2015, the majority of influenza A(H3N2) viruses alone carried the mutation. The amplification of matrix gene for these influenza A(H3N2) viruses continuously resulted in the atypically shaped amplification curves. The performance of the particular assay was critically affected; therefore, the assay was no longer usable as diagnostic tool for influenza virus detection. Mutations in the conserved region of influenza virus genome are more common than expected and this would need to be considered when targeting matrix gene. PMID- 28993124 TI - Learning ensemble classifiers for diabetic retinopathy assessment. AB - Diabetic retinopathy is one of the most common comorbidities of diabetes. Unfortunately, the recommended annual screening of the eye fundus of diabetic patients is too resource-consuming. Therefore, it is necessary to develop tools that may help doctors to determine the risk of each patient to attain this condition, so that patients with a low risk may be screened less frequently and the use of resources can be improved. This paper explores the use of two kinds of ensemble classifiers learned from data: fuzzy random forest and dominance-based rough set balanced rule ensemble. These classifiers use a small set of attributes which represent main risk factors to determine whether a patient is in risk of developing diabetic retinopathy. The levels of specificity and sensitivity obtained in the presented study are over 80%. This study is thus a first successful step towards the construction of a personalized decision support system that could help physicians in daily clinical practice. PMID- 28993125 TI - Psychoneuroimmunology of mental disorders. AB - The immune system is a key element in the organism's defence system and participates in the maintenance of homeostasis. There is growing interest in the aetiopathogenic and prognostic implications of the immune system in mental disorders, as previous studies suggest the existence of a dysregulation of the immune response and a pro-inflammatory state in patients with mental disorders, as well as an increased prevalence of neuropsychiatric symptoms in patients suffering from autoimmune diseases or receiving immune treatments. This study aims to conduct a narrative review of the scientific literature on the role of Psychoneuroimmunology in mental disorders, with special focus on diagnostic, prognostic and therapeutic issues. The development of this body of knowledge may bring in the future important advances in the vulnerability, aetiopathogenic mechanisms, diagnosis and treatment of some mental disorders. PMID- 28993127 TI - Retrospective cohort study of combined approach for trunk reconstruction using arteriovenous loops and free flaps. AB - Defect reconstruction of the trunk can be performed using microsurgical free flap transplantation. In cases of missing or inappropriate recipient vessels, microsurgical defect reconstruction of the trunk can be achieved by combining free flaps with arteriovenous loops. Here we present our 5-year experience of trunk reconstruction using AV loops and free flaps in a retrospective evaluation. We analyzed 32 cases of trunk reconstruction using a combined approach of free flap transplantation and arteriovenous loops between 2011 and 2016 regarding postoperative complications and perioperative course. Twenty-one patients suffered from sternal defects, 4 from presacral defects, 3 patients presented with lateral chest wall defects, 2 patients suffered from lumbosacral defects, 1 patient had a gluteal defect and 1 patient a defect at the clavicle. In all cases, free flap transplantation and arteriovenous loop creation were performed in a two-stage procedure. There were 8 thromboses of the arteriovenous loops with 4 flap failures. Only 1 flap loss was located in the sternal region, whereas one presacral flap and both lumbosacral flaps were lost. Reconstruction of large soft tissue defects of the trunk by a combined approach with an arteriovenous loop creation and consecutive free flap transplantation represents a reliable procedure in ventral and posterior cranial localization, whereas in the caudal posterior region, AV loop thrombosis can occur. Therefore, to minimize flap loss, a two-stage procedure should be performed. PMID- 28993126 TI - Per- and polyfluoroalkyl substances in sera from children 3 to 11 years of age participating in the National Health and Nutrition Examination Survey 2013-2014. AB - Several per- and polyfluoroalkyl substances (PFAS) have been measured in U.S. National Health and Nutrition Examination Survey (NHANES) participants 12 years of age and older since 1999-2000, but PFAS data using NHANES individual samples among children younger than 12 years do not exist. To obtain the first nationally representative PFAS exposure data in U.S. children, we quantified serum concentrations of 14 PFAS including perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA), in a nationally representative subsample of 639 3 11year old participants in NHANES 2013-2014. We used on-line solid-phase extraction coupled to isotope dilution-high performance liquid chromatography tandem mass spectrometry; limits of detection were 0.1ng/mL for all analytes. We calculated geometric mean concentrations, determined weighted Pearson correlations, and used linear regression to evaluate associations of sex, age (3 5 vs 6-11 years), race/ethnicity (Hispanic vs non-Hispanic), household income, and body mass index with concentrations of PFAS detected in more than 60% of participants. We detected PFOS, PFOA, PFHxS, and PFNA in all children at concentrations similar to those of NHANES 2013-2014 adolescents and adults, suggesting prevalent exposure to these PFAS or their precursors among U.S. 3 11year old children, most of whom were born after the phase out of PFOS in the United States in 2002. PFAS concentration differences by sex, race/ethnicity, and age suggest lifestyle differences that may impact exposure, and highlight the importance of identifying exposure sources and of studying the environmental fate and transport of PFAS. PMID- 28993130 TI - Gait retraining versus foot orthoses for patellofemoral pain: a pilot randomised clinical trial. AB - OBJECTIVES: To determine the feasibility of a clinical trial that compares a 6 week, physiotherapist-guided gait retraining program with a foot orthoses intervention in runners with patellofemoral pain. DESIGN: Pilot randomised controlled trial. METHODS: Runners aged 18-40 years with clinically diagnosed patellofemoral pain were randomly allocated to either a 6-week gait retraining intervention of increasing cadence and use of a minimalist shoe or prefabricated foot orthoses. Outcomes at baseline and 12-weeks included recruitment, retention, adherence, adverse events, global improvement, anterior knee pain scale, worst and average pain on a 100mm visual analogue scale. RESULTS: Of the 16 randomised participants, two withdrew prior to commencing treatment due to non-trial related matters (n=1 from each group) and 14 completed the pilot trial. Minor calf muscle soreness was reported by 3 participants in the gait retraining group while no adverse events were reported in the foot orthoses group. There were no deviations from the treatment protocols. There was a large between-group difference favouring gait retraining at 12-weeks in the anterior knee pain scale and the worst pain in the past week, which was reflected in the number needed-to-treat of 2. CONCLUSIONS: This study supports the feasibility of a trial comparing gait retraining with foot orthoses and provides point estimates of effect that informs the design and planning of a larger clinical trial. It appears that a 6-week gait retraining program has a clinically meaningful effect on runners with patellofemoral pain when compared to an evidence-based treatment of foot orthoses. PMID- 28993129 TI - Separating the agony from ecstasy: R(-)-3,4-methylenedioxymethamphetamine has prosocial and therapeutic-like effects without signs of neurotoxicity in mice. AB - S,R(+/-)-3,4-methylenedioxymethamphetamine (SR-MDMA) is an amphetamine derivative with prosocial and putative therapeutic effects. Ongoing clinical trials are investigating it as a treatment for post-traumatic stress disorder (PTSD) and other conditions. However, its potential for adverse effects such as hyperthermia and neurotoxicity may limit its clinical viability. We investigated the hypothesis that one of the two enantiomers of SR-MDMA, R-MDMA, would retain the prosocial and therapeutic effects but with fewer adverse effects. Using male Swiss Webster and C57BL/6 mice, the prosocial effects of R-MDMA were measured using a social interaction test, and the therapeutic-like effects were assessed using a Pavlovian fear conditioning and extinction paradigm relevant to PTSD. Locomotor activity and body temperature were tracked after administration, and neurotoxicity was evaluated post-mortem. R-MDMA significantly increased murine social interaction and facilitated extinction of conditioned freezing. Yet, unlike racemic MDMA, it did not increase locomotor activity, produce signs of neurotoxicity, or increase body temperature. A key pharmacological difference between R-MDMA and racemic MDMA is that R-MDMA has much lower potency as a dopamine releaser. Pretreatment with a selective dopamine D1 receptor antagonist prevented SR-MDMA-induced hyperthermia, suggesting that differential dopamine signaling may explain some of the observed differences between the treatments. Together, these results indicate that the prosocial and therapeutic effects of SR MDMA may be separable from the stimulant, thermogenic, and potential neurotoxic effects. To what extent these findings translate to humans will require further investigation, but these data suggest that R-MDMA could be a more viable therapeutic option for the treatment of PTSD and other disorders for which SR MDMA is currently being investigated. PMID- 28993131 TI - Impact of physical fitness and body composition on injury risk among active young adults: A study of Army trainees. AB - OBJECTIVES: To determine the combined effects of physical fitness and body composition on risk of training-related musculoskeletal injuries among Army trainees. DESIGN: Retrospective cohort study. METHODS: Rosters of soldiers entering Army basic combat training (BCT) from 2010 to 2012 were linked with data from multiple sources for age, sex, physical fitness (heights, weights (mass), body mass index (BMI), 2 mile run times, push-ups), and medical injury diagnoses. Analyses included descriptive means and standard deviations, comparative t-tests, risks of injury, and relative risks (RR) and 95% confidence intervals (CI). Fitness and BMI were divided into quintiles (groups of 20%) and stratified for chi-square (chi2) comparisons and to determine trends. RESULTS: Data were obtained for 143,398 men and 41,727 women. As run times became slower, injury risks increased steadily (men=9.8-24.3%, women=26.5-56.0%; chi2 trends (p<0.00001)). For both genders, the relationship of BMI to injury risk was bimodal, with the lowest risk in the average BMI group (middle quintile). Injury risks were highest in the slowest groups with lowest BMIs (male trainees=26.5%; female trainees=63.1%). Compared to lowest risk group (average BMI with fastest run-times), RRs were significant (male trainees=8.5%; RR 3.1, CI: 2.8-3.4; female trainees=24.6%; RR 2.6, CI: 2.3-2.8). Trainees with the lowest BMIs exhibited highest injury risks for both genders and across all fitness levels. CONCLUSIONS: While the most aerobically fit Army trainees experience lower risk of training related injury, at any given aerobic fitness level those with the lowest BMIs are at highest risk. This has implications for recruitment and retention fitness standards. PMID- 28993132 TI - Screen Failure Rates in Contemporary Randomized Clinical Phase II/III Therapeutic Trials in Genitourinary Malignancies. AB - BACKGROUND: Screen failures, defined as individuals who undergo screening but are not enrolled in a clinical trial, incur significant costs without contributing valuable data to the study. Despite these costs, there are few published data about the rate or reasons for screen failures in advanced genitourinary cancer clinical trials. MATERIALS AND METHODS: We reviewed 50 phase II and III trials in advanced genitourinary cancers conducted between 1999 and 2016. RESULTS: Of the 50 trials, only 48% (24 of 50) published screen failure rates: 68% (13 of 19) of those in prostate cancer, 33% (6 of 18) in kidney cancer, and 58% (5 of 13) in bladder cancer. Among the phase III trials in prostate cancer, the mean screen failure rate was 26% (range, 12%-45%). The main reason for screen failure was reported as ineligibility. Among the phase III trials in kidney cancer, the mean screen failure rate was 25% (range, 21%-29%), with the most frequent reasons being ineligibility and patient refusal. Among the phase II/III trials in bladder cancer, the mean screen failure rate was 19% (range, 4%-28%), with the main reasons being ineligibility and patient refusal. CONCLUSION: Contemporary trials in genitourinary cancer reported screen failure rates of approximately 20% to 30%. Many trials did not report on the numbers of, and reasons for, screen failures. Greater standardization of definitions, methods, and reporting are needed to better understand and decrease screen failure rates in genitourinary cancer clinical trials. PMID- 28993133 TI - Physics responsible for heating efficiency and self-controlled temperature rise of magnetic nanoparticles in magnetic hyperthermia therapy. AB - Magnetic nanoparticles as heat-generating nanosources in hyperthermia treatment are still faced with many drawbacks for achieving sufficient clinical potential. In this context, increase in heating ability of magnetic nanoparticles in a biologically safe alternating magnetic field and also approach to a precise control on temperature rise are two challenging subjects so that a significant part of researchers' efforts has been devoted to them. Since a deep understanding of Physics concepts of heat generation by magnetic nanoparticles is essential to develop hyperthermia as a cancer treatment with non-adverse side effects, this review focuses on different mechanisms responsible for heat dissipation in a radio frequency magnetic field. Moreover, particular attention is given to ferrite-based nanoparticles because of their suitability in radio frequency magnetic fields. Also, the key role of Curie temperature in suppressing undesired temperature rise is highlighted. PMID- 28993134 TI - Sepsis caused by bloodstream infection in patients in the intensive care unit: the impact of inactive empiric antimicrobial therapy on outcome. AB - BACKGROUND: Sepsis is one of the leading causes of death in the UK. AIMS: To identify the rate of inactive antimicrobial therapy (AMT) in the intensive care unit (ICU) and whether inactive AMT has an effect on in-hospital mortality, ICU mortality, 90-day mortality and length of hospital stay. A further aim was to identify risk factors for receiving inactive AMT. METHODS: This was a retrospective observational study conducted at Glasgow Royal Infirmary ICU between January 2010 and December 2013. In total, 12,000 blood cultures were taken over this time period, of which 127 were deemed clinically significant. Multi-variate logistic regression was used to identify risk factors independently associated with mortality. Univariate analysis followed by multi-variate analysis was performed to identify risk factors for receiving inactive AMT. RESULTS: The rate of inactive AMT was 47% (N = 60). Multi-variate analysis showed that receiving antibiotics within the first 24h of ICU admission led to reduced mortality [relative risk 1.70, 95% confidence interval (CI) 1.19-2.44]. Furthermore, it showed that severity of illness (as defined by SIRS criteria sepsis vs septic shock) increased mortality [odds ratio (OR) 9.87, 95% CI 1.73 55.5]. However, inactive AMT did not increase mortality (OR 1.07, 95% CI 0.47 2.41) or length of hospital stay (53.2 vs 69.1 days, P = 0.348). Fungal bloodstream infection was found to be a risk factor for receiving inactive AMT (OR 5.10, 95% CI 1.29-20.14). CONCLUSION: Mortality from sepsis is influenced by multiple factors. This study was unable to demonstrate that inactive AMT had an effect on mortality in sepsis. PMID- 28993135 TI - Laparoscopic cholecystectomy versus transvaginal natural orifice transluminal endoscopic surgery cholecystectomy: results of a prospective comparative single center study. AB - BACKGROUND AND AIMS: Laparoscopic cholecystectomy (LC) in female individuals has been challenged recently by transvaginal natural orifice transluminal endoscopic surgery cholecystectomy (TVC). TVC has not been widely accepted as a standard procedure, even though it is reported to be a safe and painless alternative to LC. This prospective comparative study aims to not only prove equality of TVC and LC but to underline the advantages of TVC over LC with regard to postoperative pain. METHODS: This study presents an analysis of a single-center and single surgeon study with 226 unselected consecutive cholecystectomies performed as either TVC or LC. RESULTS: A total of 226 female patients underwent surgery with either LC (136 cases) or TVC (90 cases). There were no postoperative adverse events. Twenty-two patients (24.2%) in the TVC group indicated 0 (no pain) on a visual analog scale postoperatively, whereas only 5 patients (3.7%) did so in the LC group (P = < .0001). Overall consumption of non-steroidal anti-inflammatory drugs was significantly less (P < .0001; t test) in the TVC group (mean, 1.2 +/- 0.11 g) compared with the LC group (mean, 2.1 +/- 0.1 g). Twenty-three patients (25.5%) in the TVC group needed no postoperative analgesics at all. CONCLUSIONS: TVC is a safe and painless procedure for patients with symptomatic cholelithiasis who are from various ethnic and cultural origins. This benefit, along with an equal safety profile compared with LC, should pave the way for wider application of TVC in women. PMID- 28993136 TI - Rebamipide solution: a novel submucosal injection material to promote healing speed and healing quality of ulcers induced by endoscopic submucosal dissection. AB - BACKGROUND AND AIMS: Rebamipide is administered perorally to protect the gastric mucosa. We assessed the efficacy and safety of a novel rebamipide solution as a submucosal injection material for endoscopic submucosal dissection (ESD) using an in vivo porcine model. METHODS: An endoscopist blinded to the test agents performed ESDs of hypothetical 30 mm lesions using a 2% rebamipide solution at 2 sites (rebamipide group) and a saline solution at 2 other sites (control group) in the stomachs of 8 pigs. The technical outcomes were compared between the 2 groups. The gastric ulcer stages were evaluated by endoscopy once weekly for 4 weeks after the ESD to determine the healing score (1-6). The pigs were killed at 1 week (n = 2), 2 weeks (n = 2), and 4 weeks (n = 4) after the ESD for pathologic evaluation of ESD-induced ulcers and scarring. RESULTS: There were no significant differences in any of the technical outcomes between the 2 groups, and no adverse events related to the ESD in any of the animals. The healing score was significantly higher in the rebamipide group than in the control group at 2 weeks (P = .027), 3 weeks (P = .034), and 4 weeks (P = .012). In the histopathologic assessment, fibrosis was significantly less extensive in the rebamipide group than in the control group at 2 weeks (P = .02) and 4 weeks (P = .04). CONCLUSIONS: The rebamipide solution appeared to promote both the speed and quality of healing of ESD-induced ulcers by suppressing fibrosis. PMID- 28993137 TI - Endoscopic submucosal dissection for early Barrett's neoplasia: a meta-analysis. AB - BACKGROUND AND AIMS: The role of endoscopic submucosal dissection (ESD) in Barrett's esophagus (BE) is not well established. This meta-analysis aimed to evaluate the safety and efficacy of ESD for the management of early BE neoplasia. METHODS: Three online databases were searched. The Cochran Q test and I2 were used to test for heterogeneity. Pooling was conducted using either fixed- or random-effects models depending on heterogeneity across studies. For the main outcomes, potential sources of heterogeneity were evaluated via linear regression analysis. RESULTS: Eleven studies (501 patients, 524 lesions) were included. Mean lesion size was 27 mm (95% confidence interval [CI], 20.9-33.1). Pooled estimate for en bloc resection was 92.9% (95% CI, 90.3%-95.2%). The pooled R0 (complete) and curative resection rates were 74.5% (95% CI, 66.3%-81.9%) and 64.9% (95% CI, 55.7%-73.6%), respectively. There was no association between R0 or curative resection rates and study setting (Asia vs West), length of BE, lesion characteristics, procedural time, or length of follow-up. The pooled estimates for perforation and bleeding were 1.5% (95% CI, .4%-3.0%) and 1.7% (95% CI, .6% 3.4%), respectively. Esophageal stricture rate was 11.6% (95% CI, .9%-29.6%). Incidence of recurrence after curative resection was .17% (95% CI, 0%-.3%) at a mean follow-up 22.9 months (95% CI, 17.5-28.3). CONCLUSIONS: ESD for early BE neoplasia is associated with a high en bloc resection rate, acceptable safety profile, and low recurrence after curative resection. ESD should be considered as part of the armamentarium for the management of BE neoplasia. PMID- 28993139 TI - Rapid quantification of glutaminase 2 (GLS2)-related metabolites by HILIC-MS/MS. AB - Glutamine, glutamate and glutathione are key modulators of excessive oxidative stress in tumor cells. In this study, we developed a rapid and accurate HILIC MS/MS method to simultaneously determine concentrations of cellular glutamine, glutamate and glutathione. A bared silica HILIC column was employed to analyze these polar metabolites. The LC-MS parameters were optimized to achieve high sensitivity and selectivity. The analysis can be completed within 4 min under optimal conditions. The method was validated in terms of accuracy, precision, and linearity. Intra-day (n = 9) precision was within 2.68-6.24% among QCs. Inter-day precision (n = 3) was below 12.4%. The method accuracy was evaluated by the recovery test, and the accuracy for three analytes were between 91.6 and 110%. The developed method was applied to study antioxidant function of GLS2 in non small cell lung cancer cells. Changes in concentrations of glutamine, glutamate and glutathione revealed that the overexpression of GLS2 could effectively decrease oxidative stress. In summary, this study developed a rapid HILIC-MS/MS method for quantification of GLS2-related metabolites that could facilitate elucidation of the role of GLS2 in tumor development. PMID- 28993138 TI - The impact of imaging modality (CT vs MRI) and patient position (supine vs prone) on tangential whole breast radiation therapy planning. AB - PURPOSE: The purpose of this study was to evaluate the impact of magnetic resonance imaging (MRI) versus computed tomography (CT)-derived planning target volumes (PTVs), in both supine and prone positions, for whole breast (WB) radiation therapy. METHODS AND MATERIALS: Four WB radiation therapy plans were generated for 28 patients in which PTVs were generated based on CT or MRI data alone in both supine and prone positions. A 6-MV tangential intensity modulated radiation therapy technique was used, with plans designated as ideal, acceptable, or noncompliant. Dose metrics for PTVs and organs at risk were compared to analyze any differences based on imaging modality (CT vs MRI) or patient position (supine vs prone). RESULTS: With respect to imaging modality 2/11 whole breast planning target volume (WB_PTV) dose metrics (percentage of PTV receiving 90% and 110% of prescribed dose) displayed statistically significant differences; however, these differences did not alter the average plan compliance rank. With respect to patient positioning, the odds of having an ideal plan versus a noncompliant plan were higher for the supine position compared with the prone position (P = .026). The minimum distance between the seroma cavity planning target volume (SC_PTV) and the chest wall was increased with prone positioning (P < .001, supine and prone values 1.1 mm and 8.7 mm, respectively). Heart volume was greater in the supine position (P = .005). Heart doses were lower in the supine position than prone (P < .01, mean doses 3.4 +/- 1.55 Gy vs 4.4 +/- 1.13 Gy for supine vs prone, respectively). Mean lung doses met ideal dose constraints in both positions, but were best spared in the prone position. The contralateral breast maximum dose to 1cc (D1cc) showed significantly lower doses in the supine position (P < .001, 4.64 Gy vs 9.51 Gy). CONCLUSIONS: Planning with PTVs generated from MRI data showed no clinically significant differences from planning with PTVs generated from CT with respect to PTV and doses to organs at risk. Prone positioning within this study reduced mean lung dose and whole heart volumes but increased mean heart and contralateral breast doses compared with supine. PMID- 28993140 TI - Application of RT-PCR and MALDI-TOF MS for the detection of RNA luteovirus. AB - There is a need for rapid and less expensive methods to identify RNA viruses, including luteoviruses, for practical use in agriculture and quarantine. The mass spectrometric cleaved amplified polymorphic sequence (MS-CAPS) method, which detects enzymatically cleaved amplicons by matrix-assisted laser desorption/ionization mass spectrometry, was herein used together with a short RT PCR to detect luteovirus in only 90 min. In addition, the matrixes 2',4',6' trihydroxyacetophene and 3-hydroxypicolinic acid were compared for their effectiveness in the analysis of short single-stranded biotinylated DNA obtained by a MS-CAPS reaction. PMID- 28993141 TI - Therapeutic inertia amongst general practitioners with interest in diabetes. AB - INTRODUCTION: As the therapeutic options in the management of type 2 diabetes increase, there is an increase confusion among health care professionals, thus leading to the phenomenon of therapeutic inertia. This is the failure to escalate or de-escalate treatment when the clinical need for this is required. It has been studied extensively in various settings, however, it has never been reported in any studies focusing solely on primary care physicians with an interest in diabetes. This group is increasingly becoming the focus of managing complex diabetes care in the community, albeit with the support from specialists. METHODS: In this retrospective audit, we assessed the prevalence of the phenomenon of therapeutic inertia amongst primary care physicians with an interest in diabetes in UK. We also assessed the predictive abilities of various patient level characteristics on therapeutic inertia amongst this group of clinicians. RESULTS: Out of the 240 patients reported on, therapeutic inertia was judged to have occurred in 53 (22.1%) of patients. The full model containing all the selected variables was not statistically significant, p=0.59. So the model was not able to distinguish between situations in which therapeutic inertia occurred and when it did not occur. None of the patient level characteristics on its own was predictive of therapeutic inertia. CONCLUSION: Therapeutic inertia was present only in about a fifth of patient patients with diabetes being managed by primary care physicians with an interest in diabetes. PMID- 28993142 TI - Ghrelin upregulates the phosphorylation of the GluN2B subunit of the NMDA receptor by activating GHSR1a and Fyn in the rat hippocampus. AB - Ghrelin and its receptor GHSR1a have been shown to exert numerous physiological functions in the brain, in addition to the well-established orexigenic role in the hypothalamus. Earlier work indicated that ghrelin stimulated the phosphorylation of the GluN1 subunit of the NMDA receptor (NMDAR) and enhanced synaptic transmission in the hippocampus. In the present study, we report that the exogenous application of ghrelin increased GluN2B phosphorylation. This increase was independent of GluN2B subunit activity or NMDAR channel activity. However, it depended on the activation of GHSR1a and Fyn as it was blocked by D Lys3-GHRP-6 and PP2, respectively. Inhibitors for G-protein-regulated second messengers, such as Rp-cAMP, H89, TBB, ryanodine, and thapsigargin, unexpectedly enhanced GluN2B phosphorylation, suggesting that cAMP, PKA, casein kinase II, and cytosolic calcium signaling may oppose to the effect of ghrelin on the phosphorylation of GluN2B. Our findings suggest that 1) GluN2B is likely a molecular target of ghrelin and GHSR1a-driven signaling cascades, and 2) the ghrelin-mediated phosphorylation of GluN2B depends on Fyn activation under complex negative regulation by other second messengers. PMID- 28993143 TI - Ceftolozane/tazobactam activity against drug-resistant Enterobacteriaceae and Pseudomonas aeruginosa causing healthcare-associated infections in the Asia Pacific region (minus China, Australia and New Zealand): report from an Antimicrobial Surveillance Programme (2013-2015). AB - The aim of this study was to evaluate the in vitro activity of ceftolozane/tazobactam and comparator agents tested against Enterobacteriaceae and Pseudomonas aeruginosa isolates from patients in the Asia-Pacific (APAC) region with healthcare-associated infections. Ceftolozane/tazobactam is an antipseudomonal cephalosporin combined with a well-established beta-lactamase inhibitor. A total of 1963 Gram-negative organisms (489 P. aeruginosa and 1474 Enterobacteriaceae) were consecutively collected using a prevalence-based approach from 14 medical centres in the APAC region. Antimicrobial susceptibility testing was performed by broth microdilution method as described by the CLSI and the results were interpreted according to EUCAST and CLSI breakpoint criteria. Ceftolozane/tazobactam [MIC50/90, 0.25/4 ug/mL; 89.2/85.8% susceptible (CLSI/EUCAST)] and meropenem [MIC50/90, <=0.06/<=0.06 ug/mL; 96.3/96.5% susceptible (CLSI/EUCAST)] were the most active compounds tested against Enterobacteriaceae. Isolates displayed susceptibility rates to other beta-lactam agents ranging from 85.8/81.0% for piperacillin/tazobactam to 74.4/72.7% for cefepime and 72.8/68.1% for ceftazidime using CLSI/EUCAST breakpoints. Among the Enterobacteriaceae isolates, 3.6% were carbapenem-resistant Enterobacteriaceae (CRE) and 25.6% exhibited an extended-spectrum beta-lactamase (ESBL) non-CRE phenotype. Ceftolozane/tazobactam showed good activity against ESBL non-CRE phenotype strains of Enterobacteriaceae (MIC50/90, 0.5/16 ug/mL), but not against isolates with a CRE phenotype (MIC50/90, >32/>32 ug/mL). Ceftolozane/tazobactam was the most potent (MIC50/90, 0.5/4 ug/mL) beta-lactam agent tested against P. aeruginosa isolates, inhibiting 90.8% at an MIC of <=4 ug/mL. Pseudomonas aeruginosa exhibited high rates of susceptibility to amikacin [91.2/89.4% (CLSI/EUCAST)] and colistin [98.4/100.0% (CLSI/EUCAST)]. Ceftolozane/tazobactam was the most active beta-lactam agent tested against P. aeruginosa and demonstrated higher in vitro activity than available cephalosporins when tested against Enterobacteriaceae. PMID- 28993144 TI - MicroRNA-139 inhibits the proliferation and migration of osteosarcoma cells via targeting forkhead-box P2. AB - AIMS: Osteosarcoma (OS) is the most common primary bone malignancy that affects adolescents. Although great attention has been paid to the diagnosis of and therapy for OS, the 5-year survival rate of patients with this disease remains poor. MicroRNAs are small non-coding RNAs involved in pathogenesis and progression of human malignancies. MiR-139 has been implicated in several human cancers. However, the role played by miR-139 in pathogenesis of human OS has remained largely unknown. MAIN METHODS: Realtime PCR was used to detect the expression of miR-139. CCK-8, BrdU-ELISA and ApoTox-GloTM Triplex assay was employed to detect the proliferation and apoptosis of osteosarcoma cells. Realtime PCR, Western Blotting and luciferase report assays were conducted for the target genes analysis. KEY FINDINGS: The expression of miR-139 was reduced while the expression of forkhead-box P2 (FOXP2) was induced in both OS tissue and cell lines. The reduced level of miR-139 was correlated with tumor size, clinical stage and distant metastasis. Overexpression of miR-139 inhibited the expression of FOXP2, which suppressed cell growth, but induced apoptosis. Further, we confirmed that FOXP2 was a direct target of miR-139 by luciferase reporter assay. Knockdown of FOXP2 resulted in reduced levels of cell proliferation, but increased levels of apoptosis in vitro. SIGNIFICANCE: These findings suggest that miR-139 plays a suppressive role in the regulation of OS cell proliferation and migration via directly targeting FOXP2, which might be a potential clinical diagnostic or predictive biomarker for human OS. PMID- 28993145 TI - An inhibitory mechanism of action of a novel syringic-acid derivative on alpha melanocyte-stimulating hormone (alpha-MSH)-induced melanogenesis. AB - AIMS: To report the effects of a novel syringic-acid derivative, (R)-ethyl-2 acetamido-3-(4-hydroxy-3,5-dimethoxybenzoylthio)propanoate (EABTO), on melanin synthesis and to identify its mechanism of action in B16F1 melanoma cells. METHODS: The effects of EABTO on melanin synthesis in B16F1 cells and human epidermal melanocytes and the influence on cell-free tyrosinase activity were evaluated. EABTO-induced cellular signaling cascades were studied by western blotting. KEY FINDINGS: EABTO effectively decreased melanin synthesis in a dose dependent manner but had no effect on cell-free tyrosinase activity. EABTO significantly decreased the expression of melanogenic enzymes such as tyrosinase, tyrosinase-related protein 1 (TRP-1), and TRP-2. EABTO decreased the amounts of phosphorylated cAMP response element-binding protein (CREB) and cyclic adenosine monophosphate (cAMP), thereby inhibiting expression of microphthalmia-associated transcription factor (MITF). Moreover, EABTO upregulated phosphorylated ERK. A specific ERK pathway inhibitor, PD98059, reduced EABTO-induced ERK phosphorylation and restored the expression of MITF and melanin content. SIGNIFICANCE: EABTO inhibits melanogenesis in B16F1 melanoma cells via suppression of the cAMP-CREB pathway and activation of ERK, thus decreasing expression of MITF and of melanogenic enzymes. PMID- 28993146 TI - Exercise training reverses the negative effects of chronic L-arginine supplementation on insulin sensitivity. AB - L-Arginine has emerged as an important supplement for athletes and non-athletes in order to improve performance. Arginine has been extensively used as substrate for nitric oxide synthesis, leading to increased vasodilatation and hormonal secretion. However, the chronic consumption of arginine has been shown to impair insulin sensitivity. In the present study, we aimed to evaluate whether chronic arginine supplementation associated with exercise training would have a beneficial impact on insulin sensitivity. We, therefore, treated Wistar rats for 4weeks with arginine, associated or not with exercise training (treadmill). We assessed the somatotropic activation, by evaluating growth hormone (GH) gene expression and protein content in the pituitary, as well is GH concentration in the serum. Additionally, we evaluate whole-body insulin sensitivity, by performing an insulin tolerance test. Skeletal muscle morpho-physiological parameters were also assessed. Insulin sensitivity was impaired in the arginine treated rats. However, exercise training reversed the negative effects of arginine. Arginine and exercise training increased somatotropic axis function, muscle mass and body weight gain. The combination arginine and exercise training further decreased total fat mass. Our results confirm that chronic arginine supplementation leads to insulin resistance, which can be reversed in the association with exercise training. We provide further evidence that exercise training is an important tool to improve whole-body metabolism. PMID- 28993147 TI - Techniques of Ectopic Reservoir Placement and Their Pitfalls. AB - BACKGROUND: Ectopic placement of penile prosthesis reservoirs has become more common in patients whose space of Retzius has been compromised. AIM: To describe techniques and instruments used to place penile prosthesis reservoirs ectopically. METHODS: We present our method of placing ectopic reservoirs and review the literature for other techniques. We also catalog the instruments used for this purpose. OUTCOMES: Similar to traditional reservoir placement, successful ectopic reservoir implantation requires good cosmetic and functional success and low complication rates. RESULTS: Ectopic reservoir placement has been shown to be effective, to safely avoid bowel, bladder, and vascular injury, and to maintain excellent function and cosmesis. Multiple tools for ectopic placement have been described, but no data exist comparing their effectiveness and complications. Examples include dissection of the space anterior to the transversalis muscle using the surgeon's finger, a pediatric Yankauer suction tip, or a Foerster lung clamp. Instruments described to grasp and advance the reservoir include a sponge stick, a Foerster lung clamp, and the ectopic reservoir insertion tool (Sontec, Centennial, CO, USA). The effect of different instruments on the integrity of reservoir has not been extensively studied. CLINICAL IMPLICATIONS: Attention to technique and the instruments used to dissect the ectopic space and grasp the reservoir are crucial to successful ectopic reservoir placement. STRENGTHS AND LIMITATIONS: Reports of vascular, bowel, or bladder injuries during ectopic placement are exceedingly rare, as are reports of injury to reservoirs caused by traumatic grasping. However, no methods or tools have been compared in head-to-head trials. CONCLUSION: Ectopic placement is safe and effective, but differences between methods and instruments have not been delineated. Thirumavalavan N, Gross MS, Munarriz R. Techniques of Ectopic Reservoir Placement and Their Pitfalls. J Sex Med 2017;14:1451-1454. PMID- 28993148 TI - The Sexual Event Diary (SED): Development and Validation of a Standardized Questionnaire for Assessing Female Sexual Functioning During Discrete Sexual Events. AB - BACKGROUND: The efficacy of on-demand drugs for hypoactive sexual desire disorder (HSDD) or female sexual interest/arousal disorder (FSIAD) should be assessed using a validated instrument that assesses the discrete sexual events during which the on-demand drug is taken. AIM: To develop and validate an event log for measuring sexual satisfaction and sexual functioning of discrete sexual events. METHODS: Psychometric assessment was carried out on data of 10,959 Sexual Event Diaries (SEDs) collected during three clinical trials in a total of 421 women with HSDD. Cognitive debriefing interviews were held with 16 women with HSDD. OUTCOMES: Item scores of the SED at the event level and at the subject level, summarized item scores of women during the baseline establishment and active treatment periods, and score changes in women from baseline establishment to active treatment. RESULTS: Several items of the initial 16-item SED items showed weak validity. The 16-item SED was refined to the 11-item SED. The reliability, content, and convergent validity of the 11-item SED were confirmed. For most 11 item SED item scores, the ability to discriminate between known groups was confirmed. Larger mean score changes from the baseline establishment period were found in those with than in those without known benefit from the medication, and Guyatt effect sizes ranged from 0.73 to 1.58, thereby demonstrating the ability to detect change. CLINICAL TRANSLATION: The SED is a good tool for assessing sexual function during a discrete sexual event and for assessing the sexual function of women over longer periods. STRENGTHS AND LIMITATIONS: The validation of the SED was performed on data from nearly 11,000 sexual events, gathered as part of a drug development program for HSDD and FSIAD. This amount of data provides very robust results when related to drug use for HSDD and FSIAD, but caution is advised when generalizing the validity of the SED directly to other areas of research (eg, recreational drug use and sexual risky behaviors), because such data were not used in this validation. CONCLUSIONS: The 11-item SED is a reliable, valid, and responsive instrument and suitable for use in evaluating the effects of on-demand drugs in women with HSDD or FSIAD. van Nes Y, Bloemers J, van der Heijden PGM, et al. The Sexual Event Diary (SED): Development and Validation of a Standardized Questionnaire for Assessing Female Sexual Functioning During Discrete Sexual Events. J Sex Med 2017;14:1438-1450. PMID- 28993149 TI - Relationship of Blood Pressure and Erectile Dysfunction in Men Without Previously Diagnosed Hypertension. AB - BACKGROUND: Erectile dysfunction (ED) is the most common male sexual disorder that affects all age groups and has a close association with essential hypertension. AIM: To characterize the relation of blood pressure and ED in detail. METHODS: A cross-sectional population-based study of 45- to 70-year-old men without previously diagnosed hypertension, cardiovascular diseases, renal disease, or diabetes was conducted from 2005 to 2007 in southwestern Finland. A total of 665 men with at least one cardiovascular risk factor were studied. ED was defined by the five-item International Index of Erectile Function. OUTCOMES: We found a U-shaped association between diastolic blood pressure (DBP) and prevalence of ED. RESULTS: The average age of the study subjects was 56 +/- 6 years and 52% had ED. After adjustment for age, cohabitation status, education, fasting plasma glucose level, waist circumference, and prevalence of depressive symptoms, the curve relating DBP to the prevalence of ED was U-shaped with a nadir of DBP 90 mm Hg. CLINICAL IMPLICATIONS: Our findings emphasize the importance of blood pressure measurement in the physical examination of men with ED. STRENGTHS AND LIMITATIONS: This was a cross-sectional study, which prevents the evaluation of causality between ED and hypertension. However, this community based study population is well defined and the anthropologic measurements were made by trained medical staff. CONCLUSION: We found a U-shaped correlation between ED and DBP, which confirms the link between ED and hypertension. Heikkila A, Kaipia A, Venermo M, et al. Relationship of Blood Pressure and Erectile Dysfunction in Men Without Previously Diagnosed Hypertension. J Sex Med 2017;14:1336-1341. PMID- 28993152 TI - Phenytoin repositioned in wound healing: clinical experience spanning 60 years. AB - Drug repositioning is hot, and much development time and money can be spared if one selects an old drug and explores the efficacy and safety in a new indication. Phenytoin is studied and repositioned in many disorders after the initial indication epilepsy (from 1937). Its repositioning in depression was put in the spotlight by the Wall Street icon Jack Dreyfus, already in the 1970s. Innovations in the field of phenytoin still appear to be possible for a number of indications such as wound healing, bipolar disorder and aggression, and via a topical formulation for neuropathic pain. We will discuss wound healing and identified a number of critical issues related to its repositioning in this indication. PMID- 28993151 TI - Using a SMALP platform to determine a sub-nm single particle cryo-EM membrane protein structure. AB - The field of membrane protein structural biology has been revolutionized over the last few years with a number of high profile structures being solved using cryo EM including Piezo, Ryanodine receptor, TRPV1 and the Glutamate receptor. Further developments in the EM field hold the promise of even greater progress in terms of greater resolution, which for membrane proteins is still typically within the 4-7A range. One advantage of a cryo-EM approach is the ability to study membrane proteins in more "native" like environments for example proteoliposomes, amphipols and nanodiscs. Recently, styrene maleic acid co-polymers (SMA) have been used to extract membrane proteins surrounded by native lipids (SMALPs) maintaining a more natural environment. We report here the structure of the Escherichia coli multidrug efflux transporter AcrB in a SMALP scaffold to sub-nm resolution, with the resulting map being consistent with high resolution crystal structures and other EM derived maps. However, both the C-terminal helix (TM12) and TM7 are poorly defined in the map. These helices are at the exterior of the helical bundle and form the greater interaction with the native lipids and SMA polymer and may represent a more dynamic region of the protein. This work shows the promise of using an SMA approach for single particle cryo-EM studies to provide sub-nm structures. PMID- 28993150 TI - Applications of sequence coevolution in membrane protein biochemistry. AB - Recently, protein sequence coevolution analysis has matured into a predictive powerhouse for protein structure and function. Direct methods, which use global statistical models of sequence coevolution, have enabled the prediction of membrane and disordered protein structures, protein complex architectures, and the functional effects of mutations in proteins. The field of membrane protein biochemistry and structural biology has embraced these computational techniques, which provide functional and structural information in an otherwise experimentally-challenging field. Here we review recent applications of protein sequence coevolution analysis to membrane protein structure and function and highlight the promising directions and future obstacles in these fields. We provide insights and guidelines for membrane protein biochemists who wish to apply sequence coevolution analysis to a given experimental system. PMID- 28993153 TI - TFEB activation protects against cardiac proteotoxicity via increasing autophagic flux. AB - Insufficient lysosomal removal of autophagic cargoes in cardiomyocytes has been suggested as a main cause for the impairment of the autophagic-lysosomal pathway (ALP) in many forms of heart disease including cardiac proteinopathy and may play an important pathogenic role; however, the molecular basis and the correcting strategy for the cardiac ALP insufficiency require further investigation. The present study was sought to determine whether myocardial expression and activity of TFEB, the recently identified ALP master regulator, are impaired in a cardiac proteinopathy mouse model and to determine the effect of genetic manipulation of TFEB expression on autophagy and proteotoxicity in a cardiomyocyte model of proteinopathy. We found that increased myocardial TFEB mRNA levels and a TFEB protein isoform switch were associated with marked decreases in the mRNA levels of representative TFEB target genes and increased mTORC1 activation, in mice with cardiac transgenic expression of a missense (R120G) mutant alphaB-crystallin (CryABR120G), a well-established model of cardiac proteinopathy. Using neonatal rat ventricular cardiomyocyte cultures, we demonstrated that downregulation of TFEB decreased autophagic flux in cardiomyocytes both at baseline and during CryABR120G overexpression and increased CryABR120G protein aggregates. Conversely, forced TFEB overexpression increased autophagic flux and remarkably attenuated the CryABR120G overexpression-induced accumulation of ubiquitinated proteins, caspase 3 cleavage, LDH leakage, and decreases in cell viability. Moreover, these protective effects of TFEB were dramatically diminished by inhibiting autophagy. We conclude that myocardial TFEB signaling is impaired in cardiac proteinopathy and forced TFEB overexpression protects against proteotoxicity in cardiomyocytes through improving ALP activity. PMID- 28993154 TI - Uric acid and diabetes risk among Chinese women with a history of gestational diabetes mellitus. AB - AIMS: To assess the association of uric acid (UA) with the risks of postpartum type 2 diabetes and prediabetes among women with prior gestational diabetes mellitus (GDM). METHODS: We performed a cross-sectional study of 1262 GDM women at 1-5 years after delivery using the baseline data from the Tianjin Gestational Diabetes Mellitus Prevention Program. Logistic regression models were used to estimate the association of different levels of serum UA with the risks of type 2 diabetes and prediabetes. RESULTS: The multivariable-adjusted odds ratios (ORs) across quartiles of serum UA were 1.00, 1.23 (95% confidence interval [CI] 0.55 2.78), 2.05 (95% CI 0.96-4.39), and 3.17 (95% CI 1.54-6.55) (Ptrend < 0.001) for type 2 diabetes, and 1.00, 1.50 (95% CI 1.03-2.19), 2.28 (95% CI 1.58-3.30), and 2.88 (95% CI 1.99-4.17) (Ptrend < 0.001) for prediabetes, respectively. Restricted cubic splines models showed positive linear associations of serum UA as a continuous variable with the risks of type 2 diabetes and prediabetes. This positive association was significant when stratified by healthy weight and overweight participants. CONCLUSIONS: Serum UA levels have a graded positive association with the risks of type 2 diabetes and prediabetes among Chinese with a history of GDM. PMID- 28993155 TI - Cardiac autonomic neuropathy may play a role in pathogenesis of atherosclerosis in type 1 diabetes mellitus. AB - AIMS: Cardiac autonomic neuropathy (CAN) is a frequent and severe complication of type 1 diabetes mellitus (T1DM). CAN diagnosis is associated with increased cardiovascular morbidity and mortality, often due to progressive atherosclerosis. Carotid intima media thickness (CIMT) is a surrogate marker of the atherosclerosis. The aim of our study was to evaluate the relationship between CIMT and CAN in T1DM patients. METHODS: Total of 49 T1DM patients and 45 healthy controls were examined for CAN presence and CIMT. CAN was diagnosed based on the results of Ewing test battery and spectral analysis of heart rate variability. CIMT was measured by two-dimensional ultrasound. Biochemical, anthropometric and anamnestic risk markers of atherosclerosis were evaluated. We used logistic types of generalized additive models (GAM) for statistical analysis. RESULTS: CAN was detected in 22 out of 49 T1DM patients (45%). All 45 healthy controls had normal cardiovascular autonomic tests results. CIMT was significantly positively associated with T1DM diagnosis (p=0.0251), CAN diagnosis (p=0.007), age (p<0.0001), BMI (p=0.0435) and systolic blood pressure (p=0.0098). CAN effect on CIMT interacted with the effect of T1DM. The combination of both factors significantly increased CIMT more than the sum of the individual T1DM and CAN status. CONCLUSIONS: CAN is significantly associated with higher CIMT in T1DM patients. CAN may play a role in pathogenesis of atherosclerosis in type 1 diabetes mellitus. PMID- 28993156 TI - Association between hemoglobin glycation index and hepatic steatosis in non diabetic individuals. AB - AIMS: Hemoglobin glycation index (HGI), which is the difference between the observed value of HbA1 and the predicted HbA1c based on plasma glucose levels, represents a measure of the degree of non-enzymatic glycation of hemoglobin and it has been found to be positively associated with diabetic complications. Herein we investigated whether HGI is associated with hepatic steatosis and related biomarkers in subjects without diabetes. METHODS: 1120 White individuals without diabetes were stratified in quartiles according to HGI levels. Hepatic steatosis was diagnosed by ultrasonography. RESULTS: As compared with subjects in the lowest quartile of HGI those in the intermediate and high HGI groups displayed an unfavorable cardio-metabolic risk profile having significantly higher values of body mass index (BMI), waist circumference, % fat mass, total cholesterol, triglycerides, inflammatory markers such as high sensitivity C reactive protein, erythrocytes sedimentation rate, complement C3, platelets and white blood cell count, hepatic insulin resistance assessed by the liver IR index and lower concentrations of high-density lipoprotein. HGI was positively associated with the biomarker of liver damage alanine aminotransferase, and fatty liver index, an indicator of hepatic steatosis. In a logistic regression analysis adjusted for age, gender and BMI individuals in the highest quartile of HGI exhibited a 1.6 fold increased odd of having hepatic steatosis (95% CI: 1.03-2.41; p=0.03) as compared with subjects in the lowest quartile of HGI. CONCLUSIONS: Higher levels of HGI may identify subjects without diabetes at increased risk of having hepatic steatosis. PMID- 28993157 TI - Cardiorespiratory fitness, fatness and incident diabetes. AB - AIMS: Increases in prevalence have led to a diabetes pandemic. Obesity and low cardiorespiratory fitness (CRF) are considered to be central mechanisms. We investigated if the effect of CRF on diabetes risk was equivalent across levels of fatness among healthy men. METHODS: In total 4988 middle-aged Caucasian employed men free of cardiovascular disease, diabetes and cancer were included from the Copenhagen Male Study starting in 1970-71. CRF was assessed using a sub maximal bicycle ergometer test and body mass index (BMI) was measured by height and weight. Their interaction and stratified associations with diabetes incidence were estimated in multivariable Cox-models including conventional risk factors and social class. Diabetes incidence was assessed through a national register. RESULTS: During 44 years of follow-up, 518 (10.4%) incident cases of diabetes occurred. In the multi-adjusted model, the obese had a significantly higher risk of diabetes compared to normal weight men (Hazard Ratio (HR):4.89; 95% CI: 3.62 6.61) and CRF was significantly inversely associated with diabetes (HR:0.86; 95% CI: 0.75-0.98 per 10-unit increase in ml/kg/min1 CRF). A significant multi adjusted interaction between CRF, BMI and diabetes was found (p=0.009). The stratified multi-adjusted analyses on BMI showed a significantly stronger reduced risk of diabetes per 10-unit increase in ml/kg/min1 of CRF among the obese (HR:0.58; CI: 0.38-0.89), but a weaker association among overweight (HR:0.86; CI: 0.71-1.03) and normal weight (HR:0.97; CI: 0.76-1.23). CONCLUSION: High CRF has a stronger protective effect on diabetes among obese than among normal weight men, supporting the recommendation of fitness-enhancing physical activity for preventing diabetes among the obese. PMID- 28993158 TI - High-potency block of Kir4.1 channels by pentamidine: Molecular basis. AB - Inward rectifier potassium (Kir) channels are expressed in almost all mammalian tissues and contribute to a wide range of physiological processes. Kir4.1 channel expression is found in the brain, inner ear, eye, and kidney. Loss-of-function mutations in the pore-forming Kir4.1 subunit cause an autosomal recessive disorder characterized by epilepsy, ataxia, sensorineural deafness and tubulopathy (SeSAME/EST syndrome). Despite its importance in physiological and pathological conditions, pharmacological research of Kir4.1 is limited. Here, we characterized the effect of pentamidine on Kir4.1 channels using electrophysiology, mutagenesis and computational methods. Pentamidine potently inhibited Kir4.1 channels when applied to the cytoplasmic side under inside-out patch clamp configuration (IC50 = 97nM). The block was voltage dependent. Molecular modeling predicted the binding of pentamidine to the transmembrane pore region of Kir4.1 at aminoacids T127, T128 and E158. Mutation of each of these residues reduced the potency of pentamidine to block Kir4.1 channels. A pentamidine analog (PA-6) inhibited Kir4.1 with similar potency (IC50 = 132nM). Overall, this study shows that pentamidine blocks Kir4.1 channels interacting with threonine and glutamate residues in the transmembrane pore region. These results can be useful to design novel compounds with major potency and specificity over Kir4.1 channels. PMID- 28993159 TI - Prevention of cholesterol gallstone disease by schaftoside in lithogenic diet induced C57BL/6 mouse model. AB - Schaftoside (SS) is a bioactive compound present in the Herba Desmodii Styracifolii (DS), a herb that has been used to treat cholelithiasis and urolithiasis in Chinese medicine. Whether SS inhibits cholesterol (Ch) gallstone formation has not been investigated. This study examined the effects of oral intake of SS on Ch gallstone formation in C57BL/6 mice fed a lithogenic diet. The rate of gallstone formation was recorded. Levels of Ch, triglycerides (TG) and bile salts (BS) were measured in the bile and serum. Liver histopathology was examined microscopically, and mRNA expression levels of key genes involved in cholesterol and bile metabolism were determined by qPCR. Mice fed SS were protected against gallstone formation, had increased biliary levels of BS, and reduced biliary Ch levels, resulting in a lower Ch saturation index (CSI). In addition, mice fed SS had lower serum TG and Ch levels, increased mRNA expression of liver X receptor alpha, ATP binding cassette transporter 5/8 (ABCG5/8), and ileal bile acid binding protein (IBABP) in the ileum, and of farnesoid X receptor and bile salt export protein (BSEP) in the liver and ileum. SS also protected against histologically determined liver damage. Overall, these data indicate that SS protects against Ch gallstone formation in mice, and that the effect is mediated by activation of ileal liver X receptor alpha and hepatic farnesoid X receptor. PMID- 28993160 TI - Inhibition of morphine tolerance by MrgC receptor via modulation of interleukin 1beta and matrix metalloproteinase 9 in dorsal root ganglia in rats. AB - Opiate tolerance is a critical issue in pain management. Previous studies show that activation of Mas-related gene (Mrg) C receptor can modulate the development of morphine tolerance. This study was designed to investigate the underlying mechanism(s). Intrathecal (i.t.) administration of morphine (20ug) increased the expression of interleukin-1beta (IL-1beta) and matrix metalloproteinase-9 (MMP-9) in small- and medium-sized neurons in dorsal root ganglia (DRG). Co administration of bovine adrenal medulla 8-22 (BAM8-22), a selective MrgC receptor agonist, via i.t. route inhibited the increase of IL-1beta and MMP-9 in the DRG. Exposure of DRG cultures to morphine (3.3MUM) for 3 or 5 days, but not for 1 day, induced an increase in MMP-9 mRNA expression. The treatment with BAM8 22 (10nM) for 20, 40 or 60min abolished chronic (5 days) morphine-induced increase of MMP-9 mRNA in the cultured DRG. The treatment with BAM8-22 for 1h inhibited chronic morphine-induced increase of MMP-9 and IL-1beta mRNA in DRG but these effects were abolished by MrgC receptor antibody. The treatment with BAM8 22 for 24 and 72h respectively inhibited and enhanced morphine-induced expression of MMP-9 and IL-1beta mRNA in the cultured DRG. The BAM8-22-induced inhibition and enhancement were abolished by MrgC receptor antibody. The results suggest that the inhibition of IL-1beta and MMP-9 expressions in DRG underlain the modulation of morphine tolerance by the acute activation of MrgC receptors. The chronic activation of MrgC receptors can facilitate morphine-induced increase of MMP-9 and IL-1beta expressions in DRG. PMID- 28993161 TI - New class of early-stage enterovirus inhibitors with a novel mechanism of action. AB - 4-dimethylamino benzoic acid (compound 12, synonym: 4EDMAB) was identified as an in vitro inhibitor of Coxsackie virus B3 (CVB3) replication in CPE-based assays (EC50 of 9.1 +/- 1.5 MUM). Next, the activity of twenty-three analogues was assessed, their structure-activity relationship was deduced and a more potent analogue was identified (EC50 of 2.6 +/- 0.5 MUM). The antiviral activity of 4EDMAB was further confirmed by quantifying viral RNA yield. Time-of-drug addition assay revealed that 4EDMAB exerts its antiviral activity at the early stages of virus replication. Six compound-resistant viruses were selected and genotyped and all the mutations appeared to be in the capsid protein VP1. Reverse engineering showed that single mutants Y75C, A88V, A98V, D133N and R219K were respectively 15-, 2-, 4-, 17- and 76-fold resistant to 4EDMAB. The compound protected both wild type (WT) CVB3 and the five resistant mutants from heat inactivation. The plaque size produced by the A88V, D133N and R219K mutants was smaller than that of WT and these mutants were also more heat-sensitive than WT in the absence of the compound. These findings suggest that these three mutations increase virion capsid flexibility and compensate for the stabilizing effects of 4EDMAB. Molecular modelling suggests that the compound binds to a small cavity in VP1, which is different from the hydrophobic pocket in the canyon where typical capsid binders (such as pleconaril) bind. Modelling studies also suggest a direct ionic interaction between the negatively charged carboxylic group of 4EDMAB and the positively charged guanidino group of arginine 219. Moreover, the in vitro combination of 4EDMAB and pleconaril resulted in synergistic antiviral effect. In conclusion, 4EDMAB is a novel early-stage inhibitor, which targets VP1 with a mechanism that is different from that of known capsid binders. PMID- 28993162 TI - Stability of Spinal Bone Lesions in Patients With Multiple Myeloma After Radiotherapy-A Retrospective Analysis of 130 Cases. AB - BACKGROUND: The objective of the present retrospective analysis was the response evaluation regarding bone density and stability of patients with osteolytic spinal bone lesions due to multiple myeloma after palliative radiotherapy (RT). PATIENTS AND METHODS: Patients with multiple myeloma who had undergone spinal RT from March 2003 to May 2016 were analyzed before and 3 and 6 months after RT. Assessment of spinal stability and bone density was performed using the internationally recognized Taneichi scoring system and measurement of bone density using computed tomography imaging-based Hounsfield units. For statistical analysis, we used the Bowker test, McNemar test, and kappa statistics to detect possible asymmetries in the distribution of the Taneichi score over time. We used the Student t test for comparison of the density values (Hounsfield units) before and after treatment. Toxicity was evaluated using the Common Terminology Criteria for Adverse Events, version 4.0. Additionally, overall survival was calculated using the Kaplan-Meier method. RESULTS: We evaluated 130 patients (69% male; 31% female) with multiple myeloma and a median age of 58 years. The median follow-up period was 41 months. Before treatment, 51% of the lesions were classified as unstable. At 3 and 6 months after RT, this rate had decreased to 41% (P = .0047) and 24% (P = .2393), respectively. The computed tomography measurements showed a significant increase in bone density at 3 and 6 months after RT. Acute RT-related grade 1 and 2 complications were detected in 34% of patients. Late side effects (grade 1-2) were detected in 23% of the patients. No severe grade 3 or 4 acute or late toxicities were identified. The median overall survival was 19.7 months for all patients and 6.6 months for patients with a Karnofsky performance score of <= 70%. CONCLUSION: To the best of our knowledge, ours is the first report to analyze the bone density and stability in patients with multiple myeloma after RT using a validated scoring system and computed tomography imaging. Palliative RT is an effective method resulting in a significant increase in bone density for local response and stability without severe RT-related toxicity. Furthermore, recalcification could already be detected at 3 months after treatment. PMID- 28993163 TI - TLL1 rs17047200 Increases the Risk of Fibrosis Progression in Caucasian Patients With Chronic Hepatitis C. PMID- 28993164 TI - Pre-emptive ketorolac for prevention of intraoperative shoulder pain in patients undergoing cesarean section: A double blind randomized clinical trial. AB - BACKGROUND: Shoulder pain is a commonly observed but mostly neglected consequence of cesarean section and little is known as well as explored about intraoperative shoulder pain. We conducted this randomized prospective double-blinded study to evaluate the efficacy of ketorolac in reducing the incidence and severity of intraoperative shoulder pain in patients undergoing cesarean section. METHODS: Two hundred ASA I and II patients scheduled to undergo elective cesarean section under spinal anesthesia were randomized to receive either intravenous ketorolac 30 mg (ketorolac group) or normal saline (control group). The primary outcome was the incidence of intraoperative shoulder pain. Secondary outcomes were severity of intraoperative shoulder pain, amount of intraoperative blood loss, incidence of hypotension, bradycardia and request for intraoperative rescue analgesia. RESULTS: The incidence of intraoperative shoulder pain in the control group was significantly higher than the ketorolac group (P = 0.003). Severity of shoulder pain and requests for intraoperative analgesia was significantly higher in the control group (P = 0.012, P = 0.006 respectively). Patients in the Ketorolac group experienced significantly higher incidences of bradycardia (P = 0.037). CONCLUSION: 30 mg ketorolac administered intravenously just before the operation could decrease incidence and severity of intraoperative shoulder pain in patients undergoing cesarean section. CLINICAL TRIAL REGISTRATION: ClinicalTrial.gov (Registration number: NCT02380898, first registered in 01/03/2015). PMID- 28993165 TI - Motor-sparing continuous median nerve block for hand surgery: A pediatric case. AB - Here is described a successful perioperative pain control with continuous median nerve block after flexor tendon repair surgery on 2nd finger of a child. A 9-year old patient was admitted for reconstruction surgery. The combination of median nerve block and lateral/medial antecubital cutaneous nerve blocks were performed before the surgery to cover all the surgical incision including the 2nd finger, palm, the graft site proximal to the wrist, and Kleinert traction at the nail bed. At the end of the surgery, the infusion catheter was inserted at the distal one-third to spare the muscle strength of flexor digitorum muscles. Continuous bupivacaine infusion provided complete analgesia until the postoperative day 4 without interfering the postoperative physiotherapy. The continuous median nerve block at the distal one-third of the forearm spared finger flexion, and supported effective postoperative early mobilization after zone 2 flexor tendon repair surgery. PMID- 28993166 TI - Heating treatments affect the thermal behaviour of doxorubicin loaded in PEGylated liposomes. AB - Doxil(r) is a stealth marketed PEGylated liposomal formulation, containing the anticancer drug doxorubicin. After loading via a pH gradient, fibrillar supramolecular structures of doxorubicin sulfate originates inside the core of the liposomes. Recently, the crystallinity of doxorubicin sulfate has been confirmed by high-resolution calorimetry. However, no detailed information are available on the nature of doxorubicin sulfate nanocrystals and on the effect of different thermal treatments. Thus, the aim of this work was to characterize the thermal behaviour of Doxil(r) in comparison to the unloaded liposomes using microcalorimetry, dynamic light scattering and high-resolution ultrasound spectroscopy (HR-US). Different thermal programmes were applied with the aim to highlight the effect of the treatments on the formulation. The used techniques confirmed the ordered state of doxorubicin nanocrystals inside PEGylated liposomes. Particularly, microcalorimetry and HR-US highlighted the changes in the thermal behaviour of the drug under different heating programmes. Doxorubicin nanocrystals were found to be stable after heating up to 80 degrees C, but an irreversible thermal behaviour was observed after a prolonged heating at elevated temperature (2h at 80 degrees C). The non-reversibility could be related to the formation of a different ordered structure and enhanced by the slight leakage of the drug occurring after a prolonged heating. PMID- 28993167 TI - Enhanced solubility and bioavailability of simvastatin by mechanochemically obtained complexes. AB - In the present work, complexes of simvastatin (SIM) with polysaccharide arabinogalactan (AG) or disodium salt of glycyrrhizin acid (Na2GA) have been prepared using mechanochemical technique to improve the solubility of SIM and enhance its oral bioavailability. The interactions of SIM with AG or Na2GA were investigated by FTIR, DSC, XRD and SEM. Self-association of SIM in various solvents was investigated by UV/Vis and NMR techniques. The molecular masses of supramolecular systems-inclusion complexes and micelles, which are the "hosts" for SIM molecules were measured. The parallel artificial membrane permeability assay (PAMPA) revealed a strong increasing of SIM permeability in the presence of Na2GA in comparison with pure SIM used as a control. On the other hand, the rapid storage assay (+40 degrees C for 3 months) showed that the chemical stability of SIM/AG complexes was similar to pure SIM, but SIM/Na2GA complexes had an enhanced stability. Pharmacokinetic tests in vivo on laboratory animals showed a significant increase in SIM's bioavailability after its introduction as a complex with Na2GA or AG. Moreover, SIM/AG inclusion complex performed better than SIM in reducing total cholesterol level. Therefore, the mechanochemically synthesized complexes of SIM with AG or Na2GA might have a promising future as novel formulations for hyper-cholesterolemia treatment. PMID- 28993168 TI - Selective digestive and oropharyngeal decontamination in medical and surgical ICU patients: authors' reply. PMID- 28993169 TI - Anti-tuberculosis drug combination for controlled oral delivery using 3D printed compartmental dosage forms: From drug product design to in vivo testing. AB - The design and production of an oral dual-compartmental dosage unit (dcDU) was examined in vitro and in vivo with the purpose of physically isolating and modulating the release profile of an anti-tuberculosis drug combination. Rifampicin (RIF) and isoniazid (ISO) are first line combination drugs for treatment of tuberculosis (TB) that negatively interact with each other upon simultaneous release in acidic environment. The dcDUs were designed in silico by computer aided design (CAD) and fabricated in two steps; first three-dimensional (3D) printing of the outer structure, followed by hot-melt extrusion (HME) of the drug-containing filaments. The structure of the fabricated dcDUs was visualized by scanning electron microscopy (SEM). The 3D printed compartmentalized shells were loaded with filaments containing active pharmaceutical ingredient (API) and selectively sealed to modulate drug dissolution. The drug release profile of the dcDUs was characterized by pH-transfer dissolution in vitro and pharmacokinetics studies in rats, and resulted in modified release of the APIs from the dcDUs as compared to the free filaments. Furthermore, the selective physical sealing of the compartments resulted in an effective retardation of the in vitro API release. The findings of this study support the development of controllable-by design dcDU systems for combination therapies to enable efficient therapeutic translation of oral dosage forms. PMID- 28993170 TI - College women, HPV genotyping and sexual behavior before HPV vaccination: Results from samples stored for a long time. AB - HPV is the sexually transmitted agent most common among young people, like college students. The aim of study was to associate sexual behavior characteristics of women with HPV, detected in genital samples taken before the introduction of the HPV vaccine. Female students during 2001-2005 donated genital samples and the samples were re-analyzed in 2013 for HPV genotyping by RT-PCR. The frozen storage of the students' genital samples allowed the detection of HPV DNA and its genotyping after years of sample collection. HPV prevalence was 22%, HPV16 3.9%, and HPV18 1.1%. Age, multiple sexual partners and the partner's age at first sexual intercourse were significantly associated to HPV. Students with >= 3 sexual partners and who did not use condom had 12.8 higher odds of being HPV positive. These results made possible the analysis of HPV prevalence changes, before HPV vaccine introduction. PMID- 28993171 TI - Cross-sectional study of MERS-CoV-specific RNA and antibodies in animals that have had contact with MERS patients in Saudi Arabia. AB - BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) is a newly emerged coronavirus that is associated with a severe respiratory disease in humans in the Middle East. The epidemiological profiles of the MERS-CoV infections suggest zoonotic transmission from an animal reservoir to humans. METHODS: This study was designed to investigate animal herds associated with Middle East respiratory syndrome (MERS)-infected patients in Saudi Arabia, during the last three years (2014-2016). Nasal swabs and serum samples from 584 dromedary camels, 39 sheep, 51 goats, and 2 cattle were collected. Nasal samples from camels, sheep, goats, and cattle were examined by real-time reverse transcription PCR (RT-PCR) to detect MERS-CoV RNA, and the Anti-MERS ELISA assay was performed to detect camel humeral immune response (IgG) to MERS-CoV S1 antigen infection. The complete genome sequencing of ten MERS-CoV camel isolates and phylogenetic analysis was performed. RESULTS: The data indicated that seventy five dromedary camels were positive for MERS-CoV RNA; the virus was not detected in sheep, goats, and cattle. MERS-CoV RNA from infected camels was not detected beyond 2 weeks after the first positive result was detected in nasal swabs obtained from infected camels. Anti-MERS ELISA assays showed that 70.9% of camels related to human cases had antibodies to MERS-CoV. The full genome sequences of the ten MERS-CoV camel isolates were identical to their corresponding patients and were grouped together within the larger MERS-CoV sequences cluster for human and camel isolates reported form the Arabian Peninsula. CONCLUSIONS: These findings indicate that camels are a significant reservoir for the maintenance of MERS-CoVs, and they are an important source of human infection with MERS. PMID- 28993172 TI - Hidden burden of chikungunya in North India; A prospective study in a tertiary care centre. AB - BACKGROUND: Arboviral diseases, such as chikungunya, dengue and now zika represent a public health problem, especially in tropical countries. Epidemiology of chikungunya and dengue is well known, including its social and climatic factors associated, but only few data and reports of chikungunya are available from North India. The clinical differentiation of chikungunya from dengue is no doubt challenging since both diseases can share clinical signs and symptoms leading to potential misdiagnosis of chikungunya in areas where dengue is endemic. The aim of this study was to know the seroprevalence, seasonal trends, clinical presentations of chikungunya and its co-infection with dengue virus. METHODS: This was a prospective study conducted in Varanasi, from January to December 2016. All serum samples were tested for both chikungunya and dengue IgM antibodies by MAC ELISA test. RESULTS: Total of 186 samples, out of which 108 (58%) samples were total seropositive, 23 (12.37%) samples positive for chikungunya IgM antibodies, 57 (30.65%) samples positive for dengue and 28 (15.05%) samples positive for both chikungunya and dengue. The most affected age group was 20-30 years and males were more affected than females. A seasonal peak for chikungunya and its co-infection with dengue were seen in November. CONCLUSION: In India, the seroprevalence of chikungunya is increasing. India is a rapidly developing country where adequate sanitation is required. More aggressive intervention and vigilance by health authorities is needed to decrease vector born diseases. PMID- 28993173 TI - Role of MexAB-OprM and MexXY-OprM efflux pumps and class 1 integrons in resistance to antibiotics in burn and Intensive Care Unit isolates of Pseudomonas aeruginosa. AB - BACKGROUND: The overexpression of efflux pumps and existence of class 1 integrons are the most important mechanisms that contribute to antimicrobial resistance in Pseudomonas aeruginosa especially in burn and Intensive Care Units (ICUs). The present study evaluated the role of MexAB-OprM and MexXY-OprM efflux pumps and class 1 integrons in resistance to antibiotics in burn and ICU isolates of P. aeruginosa. METHODS: Fifteen burn and forty-two ICU isolates were obtained from four hospitals in Northwest Iran. The isolates were identified and evaluated by the disk diffusion and agar dilution methods for determining antibiotic resistances. The presence of class 1 integrons and associated resistance gene cassettes were detected by PCR and sequencing of the products. The expression levels of efflux pumps were evaluated by phenotypic and genotypic (Quantitative Real-time PCR) methods. The isolates were genotyped by Random Amplified Polymorphic DNA Typing (RAPD-PCR). RESULTS: All burn isolates were integron positive and Multi-drug resistant (MDR), while 78.5% and 69% of ICU isolates were found as MDR and integron positive, respectively. The aadB gene was the most prevalent gene cassette (63.6%) followed by aacA4 (47.7%). Thirty-nine (68.4%) and 43 (75.4%) isolates exhibited an overexpression of MexAB-OprM and MexXY-OprM. Among burn isolates, 80% and 86.6% of them were mexB and mexY overexpressed, while 64.2% and 71.4% of ICU isolates exhibited mexB and mexY overexpression, correspondingly. The isolates were genotyped as 24 different RAPD profiles and were grouped into 15 clusters. CONCLUSIONS: The data suggested that class 1 integron had a more significant role than efflux pumps in resistance to beta lactams and aminoglycosides in burn and ICUs except for gentamicin in burn isolates. Based on our data, it is possible that efflux pumps were not the main cause of high-level resistance to antibiotics. PMID- 28993174 TI - Meningovascular neurosyphilis with basilar artery thrombosis in HIV patient. AB - Currently, neurosyphilis is an uncommon disease and may occur at any stage of syphilis. Co-infection of syphilis with HIV can affect the clinical course. We report a case of meningovascular neurosyphilis in a patient with HIV in whom basilar artery thrombosis and reactive VDRL in CSF were detected. Treatment with penicillin was instituted with adequate response showing clinical improvement. Neurosyphilis is a differential diagnosis in young patients with cerebral infarction, especially in HIV patients. PMID- 28993175 TI - Research to knowledge: promoting the training of physician-scientists in the biology of pregnancy. AB - Common disorders of pregnancy, such as preeclampsia, preterm birth, and fetal growth abnormalities, continue to challenge perinatal biologists seeking insights into disease pathogenesis that will result in better diagnosis, therapy, and disease prevention. These challenges have recently been intensified with discoveries that associate gestational diseases with long-term maternal and neonatal outcomes. Whereas modern high-throughput investigative tools enable scientists and clinicians to noninvasively probe the maternal-fetal genome, epigenome, and other analytes, their implications for clinical medicine remain uncertain. Bridging these knowledge gaps depends on strengthening the existing pool of scientists with expertise in basic, translational, and clinical tools to address pertinent questions in the biology of pregnancy. Although PhD researchers are critical in this quest, physician-scientists would facilitate the inquiry by bringing together clinical challenges and investigative tools, promoting a culture of intellectual curiosity among clinical providers, and helping transform discoveries into relevant knowledge and clinical solutions. Uncertainties related to future administration of health care, federal support for research, attrition of physician-scientists, and an inadequate supply of new scholars may jeopardize our ability to address these challenges. New initiatives are necessary to attract current scholars and future generations of researchers seeking expertise in the scientific method and to support them, through mentorship and guidance, in pursuing a career that combines scientific investigation with clinical medicine. These efforts will promote breadth and depth of inquiry into the biology of pregnancy and enhance the pace of translation of scientific discoveries into better medicine and disease prevention. PMID- 28993176 TI - Comparing parents' and overweight adolescents' reports on parent mealtime actions. AB - This study aimed to compare answers given by parents and their adolescent children to the Portuguese version of the Parent Mealtime Action Scale (PMAS) and to assess associations among the reported behaviors. To compare these answers, a cross-sectional study was conducted in a sample of 72 patients of the Obesity Clinic of the Division of Nutrology of the Pediatrics Department at the Federal University of Sao Paulo (Unifesp), Brazil. These patients were aged from 10 years to 19 years and 11 months, and their parents or legal guardians also participated. First, parents were interviewed and instructed to answer how often they perform each behavior measured by the PMAS (never, sometimes or always). Next, the same questions were answered by the adolescents. The general linear model (GLM) showed the effects of the interviewees and of the interaction between interviewees and sex. We also observed a triple interaction effect (sex x interviewees x categorized age). The internal reliability of the PMAS was higher for parental answers than for those given by the children. This finding is probably observed because the scale has been developed and validated to evaluate the pattern of parental responses concerning their eating practices during their children's meals. In addition, although parents believe they are engaging in certain behaviors, the effectiveness of these strategies may not be recognized by their children. Very low intraclass correlation coefficients were observed between parents' and children's answers to the original domains of the PMAS (ICC: 0.130-0.578), suggesting that the factorial structure of the PMAS may only be used to assess parental behavior, as it is not sufficiently accurate to assess the children's understanding of parent mealtime actions. PMID- 28993177 TI - DKK1 and sclerostin are early markers of relapse in multiple myeloma. AB - Recent studies have shown that Dickkopf-related protein (DKK1) and sclerostin decrease when a complete response (CR) is obtained after chemotherapy in myeloma multiple (MM). To study variations in DKK1, sclerostin and P1NP in patients treated for MM, between complete response (CR) and relapse, we carried out a prospective study ancillary to the IFM 2009 protocol (IFM). The aim of IFM was to compare progression-free survival between patients treated with chemotherapy with or without transplantation. We selected 69 patients who reached CR and relapsed. We assayed by ELISA: DKK1, sclerostin and P1NP at 3 end points T1: CR, T2: 4 months before relapse and T3: relapse. There was a significant increase in DKK1 and sclerostin between T1, T2 and T3. (DKK1 medians (IQR): T1 = 30 pmol/l (20.4 41.1), T2 = 37.4 pmol/l (29.8-49.4), p < 0.0001, T3 = 42 pmol/l (33.8-55.5), p < 0.0001 sclerostin medians (IQR): T1 = 0.57 (0.47-0.69), T2 = 0.62 ng/ml (0.53 0.79), p < 0.0001, T3 = n0.64 ng/ml (0.56-0.79), p = 0.005). No significant variation was detected in the levels of P1NP. No association was observed between the characteristics of the MM, or the treatment received and the variation between T1-T3 for DKK1, sclerostin or P1NP. A significant increase in DKK1 and sclerostin was observed four months before relapse. PMID- 28993178 TI - A user-friendly risk-score for predicting in-hospital cardiac arrest among patients admitted with suspected non ST-elevation acute coronary syndrome - The SAFER-score. AB - AIM: To develop a simple risk-score model for predicting in-hospital cardiac arrest (CA) among patients hospitalized with suspected non-ST elevation acute coronary syndrome (NSTE-ACS). METHODS: Using the Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART), we identified patients (n=242 303) admitted with suspected NSTE-ACS between 2008 and 2014. Logistic regression was used to assess the association between 26 candidate variables and in-hospital CA. A risk-score model was developed and validated using a temporal cohort (n=126 073) comprising patients from SWEDEHEART between 2005 and 2007 and an external cohort (n=276 109) comprising patients from the Myocardial Ischaemia National Audit Project (MINAP) between 2008 and 2013. RESULTS: The incidence of in hospital CA for NSTE-ACS and non-ACS was lower in the SWEDEHEART-derivation cohort than in MINAP (1.3% and 0.5% vs. 2.3% and 2.3%). A seven point, five variable risk score (age >=60 years (1 point), ST-T abnormalities (2 points), Killip Class >1 (1 point), heart rate <50 or >=100bpm (1 point), and systolic blood pressure <100mmHg (2 points) was developed. Model discrimination was good in the derivation cohort (c-statistic 0.72) and temporal validation cohort (c statistic 0.74), and calibration was reasonable with a tendency towards overestimation of risk with a higher sum of score points. External validation showed moderate discrimination (c-statistic 0.65) and calibration showed a general underestimation of predicted risk. CONCLUSIONS: A simple points score containing five variables readily available on admission predicts in-hospital CA for patients with suspected NSTE-ACS. PMID- 28993179 TI - The International Liaison Committee on Resuscitation-Review of the last 25 years and vision for the future. AB - 2017 marks the 25th anniversary of the International Liaison Committee on Resuscitation (ILCOR). ILCOR was formed in 1992 to create a forum for collaboration among principal resuscitation councils worldwide. Since then, ILCOR has established and distinguished itself for its pioneering vision and leadership in resuscitation science. By systematically assessing the evidence for resuscitation standards and guidelines and by identifying national and regional differences, ILCOR reached consensus on international resuscitation guidelines in 2000, and on international science and treatment recommendations in 2005, 2010 and 2015. However, local variation and contextualization of guidelines are evident by subtle differences in regional and national resuscitation guidelines. ILCOR's efforts to date have enhanced international cooperation, and progressively more transparent and systematic collection and analysis of pertinent scientific evidence. Going forward, this sets the stage for ILCOR to pursue its vision to save more lives globally through resuscitation. PMID- 28993181 TI - Towards a universal second-line fixed-dose combination ART. PMID- 28993182 TI - Spatial and temporal distribution of Pfmsp1 and Pfmsp2 alleles and genetic profile change of Plasmodium falciparum populations in Gabon. AB - Plasmodium population dynamics analysis may help to assess the impact of malaria control strategies deployment. In Gabon, new strategies have been introduced, but malaria is still a public health problem marked by a rebound of the prevalence in 2011. The aim of the study was to investigate the spatial and temporal distribution of P. falciparum strains in different areas in Gabon during a period of malaria transmission transition, between 2008 and 2011. A total of 109P. falciparum isolates were genotyped using nested-PCR of Pfmsp1 and Pfmsp2 genes. 3D7, FC27 and K1 allele frequencies were comparable between sites (p=0.9); those of Ro33 (93.6%; 44/47) and Mad20 (60%; 12/20) were significantly higher in isolates from Oyem (p<0.01) and Port-Gentil (p=0.02), respectively. The frequency of multiples infections (77%) and the complexity of infection (2.66+/-1.44) were the highest at Oyem. Pfmsp1 gene analysis highlighted a trend of a decreasing frequency of K1 family, in Libreville and Oyem between 2008 and 2011; while that of Ro33 (p<0.01) and Mad20 (p<0.01) increased. The prevalence of multiple infections was comparable between both periods in each site: 42.2% vs 47.6% (p=0.6) in Libreville and 57.7% vs 61.7% in Oyem (p=0.8). In contrast, in 2011, the COI tends to be higher in Libreville and did not vary in Oyem. These data confirm an extended genetic diversity of P. falciparum isolates over time and according to geographic location in Gabon. Nevertheless, the impact of the deployment of malaria control strategies on the parasites genetic profile is not clearly established here. PMID- 28993183 TI - Nucleos(t)ide analogue interruption: Alternative approach to intrahepatic set point for spontaneous control of HBV replication? PMID- 28993180 TI - Efficacy and safety of switching from boosted protease inhibitors plus emtricitabine and tenofovir disoproxil fumarate regimens to single-tablet darunavir, cobicistat, emtricitabine, and tenofovir alafenamide at 48 weeks in adults with virologically suppressed HIV-1 (EMERALD): a phase 3, randomised, non inferiority trial. AB - BACKGROUND: Simplified regimens with reduced pill burden and fewer side-effects are desirable for people living with HIV. We investigated the efficacy and safety of switching to a single-tablet regimen of darunavir, cobicistat, emtricitabine, and tenofovir alafenamide versus continuing a regimen of boosted protease inhibitor, emtricitabine, and tenofovir disoproxil fumarate. METHODS: EMERALD was a phase-3, randomised, active-controlled, open-label, international, multicentre trial, done at 106 sites across nine countries in North America and Europe. HIV-1 infected adults were eligible to participate if they were treatment-experienced and virologically suppressed (viral load <50 copies per mL for >=2 months; one viral load of 50-200 copies per mL was allowed within 12 months before screening), and patients with a history of virological failure on non-darunavir regimens were allowed. Randomisation was by computer-generated interactive web response system and stratified by boosted protease inhibitor use at baseline. Patients were randomly assigned (2:1) to switch to the open-label study regimen or continue the control regimen. The study regimen consisted of a fixed-dose tablet containing darunavir 800 mg, cobicistat 150 mg, emtricitabine 200 mg, and tenofovir alafenamide 10 mg, which was taken once per day for 48 weeks. The primary outcome was the proportion of participants with virological rebound (confirmed viral load >=50 copies per mL or premature discontinuations, with last viral load >=50 copies per mL) cumulative through week 48; we tested non inferiority (4% margin) of the study regimen versus the control regimen in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT02269917. FINDINGS: The study began on April 1, 2015, and the cutoff date for the week 48 primary analysis was Feb 24, 2017. Of 1141 patients (763 in the study group and 378 in the control group), 664 (58%) had previously received five or more antiretrovirals, including screening antiretrovirals, and 169 (15%) had previous virological failure on a non-darunavir regimen. The study regimen was non-inferior to the control for virological rebound cumulative through week 48 (19 [2.5%] of 763 patients in the study group vs eight (2.1%) of 378 patients in the control group; difference 0.4%, 95% CI -1.5 to 2.2; p<0.0001). No resistance to any study drug was observed. Numbers of discontinuations related to adverse events (11 [1%] of 763 patients in the study group vs four [1%] of 378 patients in the control group) and grade 3-4 adverse events (52 [7%] patients vs 31 [8%] patients) were similar between the two groups. There was a small non clinically relevant but statistically significant (0.2 [SD 1.1] vs 0.1 [1.1], p=0.010) difference between the two groups in change from baseline in total cholesterol to HDL-cholesterol ratio. Only one serious adverse event (pancreatitis in the study group) was deemed as possibly related to the study regimen. INTERPRETATION: Our findings show the safety and efficacy of single tablet darunavir, cobicistat, emtricitabine, and tenofovir alafenamide as a potential switch option for the treatment of HIV-1 infection in adults with viral suppression. FUNDING: Janssen. PMID- 28993184 TI - Pitfalls in the non-invasive assessment of liver fibrosis with eLIFT-FMVCTE algorithm. PMID- 28993185 TI - Reply to: "Nucleos(t)ide analogue interruption: Alternative approach to intrahepatic set point for spontaneous control of HBV replication?" PMID- 28993186 TI - Experimental oral iron administration: Histological investigations and expressions of iron handling proteins in rat retina with aging. AB - Iron is implicated in age-related macular degeneration (AMD). The aim of this study was to see if long-term, experimental iron administration with aging modifies retinal and choroidal structures and expressions of iron handling proteins, to understand some aspects of iron homeostasis. Male Wistar rats were fed with ferrous sulphate heptahydrate (500mg/kg body weight/week, oral; elemental iron availability: 20%) from 2 months of age onward until they were 19.5 month-old. At 8, 14 and 20 months of age, they were sacrificed and serum and retinal iron levels were detected by HPLC. Oxidative stress was analyzed by TBARS method. The retinas were examined for cell death (TUNEL), histology (electron microscopy) and the expressions of transferrin, transferrin receptor-1 [TFR-1], H and L-ferritin. In control animals, at any age, there was no difference in the serum and retinal iron levels, but the latter increased significantly in 14- and 20 month-old iron-fed rats, indicating that retinal iron accumulation proceeds with progression of aging (>14 months). The serum and retinal TBARS levels increased significantly with progression of aging in experimental but not in control rats. There was significant damage to choriocapillaris, accumulation of phagosomes in retinal pigment epithelium and increased incidence of TUNEL+ cells in outer nuclear layer and vacuolation in inner nuclear layer (INL) of 20 month aged experimental rats, compared to those in age-matched controls. Vacuolations in INL could indicate a long-term effect of iron accumulation in the inner retina. These events paralleled the increased expression of ferritins and transferrin and a decrease in the expression of TFR-1 in iron-fed rats with aging, thereby maintaining iron homeostasis in the retina. As some of these changes mimic with those happening in eyes with AMD, this model can be utilized to understand iron-induced pathophysiological changes in AMD. PMID- 28993187 TI - Inpatient Glucose Values: Determining the Nondiabetic Range and Use in Identifying Patients at High Risk for Diabetes. AB - BACKGROUND: Many individuals with diabetes remain undiagnosed, leading to delays in treatment and higher risk for subsequent diabetes complications. Despite recommendations for diabetes screening in high-risk groups, the optimal approach is not known. We evaluated the utility of inpatient glucose levels as an opportunistic screening tool for identifying patients at high risk for diabetes. METHODS: We retrospectively examined 462,421 patients in the US Department of Veterans Affairs healthcare system, hospitalized on medical/surgical services in 2000-2010, for >=3 days, with >=2 inpatient random plasma glucose (RPG) measurements. All had continuity of care: >=1 primary care visit and >=1 glucose measurement within 2 years before hospitalization and yearly for >=3 years after discharge. Glucose levels during hospitalization and incidence of diabetes within 3 years after discharge in patients without diabetes were evaluated. RESULTS: Patients had a mean age of 65.0 years, body mass index of 29.9 kg/m2, and were 96% male, 71% white, and 18% black. Pre-existing diabetes was present in 39.4%, 1.3% were diagnosed during hospitalization, 8.1% were diagnosed 5 years after discharge, and 51.3% were never diagnosed (NonDM). The NonDM group had the lowest mean hospital RPG value (112 mg/dL [6.2 mmol/L]). Having at least 2 RPG values >140 mg/dL (>7.8 mmol/L), the 95th percentile of NonDM hospital glucose, provided 81% specificity for identifying incident diabetes within 3 years after discharge. CONCLUSIONS: Screening for diabetes could be considered in patients with at least 2 hospital glucose values at/above the 95th percentile of the nondiabetic range (141 mg/dL [7.8 mmol/L]). PMID- 28993188 TI - The effect of killer cell immunoglobulin-like receptor genotype on outcome of hematopoietic stem cell transplantation from matched sibling. AB - The alloreactivity of natural killer (NK) cell after allogeneic hematopoietic stem cell transplantation (AHSCT) is regulated by the interaction between donor killer immunoglobulin-like receptors (KIRs) and recipient human leukocyte antigen (HLA)-class I molecules. The aim was to identify KIR genes, haplotypes and their HLA-class I ligands and to investigate their association with transplantation outcome. The study included 65 patient/donor pairs who received AHSCT from HLA matched identical siblings. KIR genotyping was done for donors using reverse sequence specific oligonucleotide probes (rSSO) coupled with luminex technology, while HLA-C genotyping was performed in patients using rSSO strip assay. In multivariate analysis, KIR2DS4 was associated with significant reduced incidence of relapse (p = .002). A trend towards reduced incidence of relapse was also observed with more than two KIR B motifs (p = .09), whereas a significant increased relapse was associated with homozygous HLA-C2 ligand compared to combined C1/C2 and C1/C1 (p = .04). Activating KIR2DS3 was associated with rapid leukocyte engraftment (p = .02). While, KIR 2DL5 was associated with decreased CMV infection (p = .03) and better platelets engraftment (p = .05). KIR genes, haplotypes and HLA-C alleles have an impact on HSCT outcome. Better selection of donors with favorable KIR genotype can improve HLA-matched sibling HSCT outcome especially for AML patients. PMID- 28993189 TI - Effect of genetic variants of OPTN in the pathophysiology of Paget's disease of bone. AB - Paget's disease of bone (PDB) is the second most frequent metabolic bone disease after osteoporosis. Genetic factors play an important role in PDB, but to date PDB causing mutations were identified only in the Sequestosome 1 gene at the PDB3 locus. OPTN has been recently associated with PDB, however little is known about the effect of genetic variants in this gene in PDB pathophysiology. By sequencing OPTN in SQSTM1 non-carriers PDB patients we found 16 SNPs in regulatory, coding and non-coding regions. One of those was found to be associated with PDB in our cohort - rs2234968. Our results show that rs2238968 effect may be explained by a change in OPTN splicing that give rise to a predicted truncated protein. We also performed functional studies on the variants located in OPTN promoter - rs3829923 and the rare variant -9906 - to investigate putative regulators of OPTN. Our results show that OPTN expression seems to be regulated by SP1, RXR, E47, and the E2F family. In conclusion, our work suggests a potential pathophysiological role of SNPs in OPTN, giving a new perspective about the regulatory mechanisms of this gene. Ultimately we discovered a new variant associated with PDB in OPTN, reinforcing the relevance of this gene for the development of this bone disease. PMID- 28993190 TI - Secretome from hypoxia-conditioned adipose-derived mesenchymal stem cells promotes the healing of gastric mucosal injury in a rodent model. AB - Studies have indicated that the definitive engraftment and transdifferentiation potential of stem cells do not seem crucial for its property of tissue repair. Our previous study showed that transplantation of adipose-derived mesenchymal stem cells (ADMSCs) enhanced the healing of sutured gastric perforation. This study aimed to investigate the paracrine role of ADMSCs in the experimental gastric mucosal injury. Normoxia-conditioned medium (Nor CM) and hypoxia (HPO) CM were obtained after culturing ADMSCs in 20% O2 and 5% O2 for 48h. Cell migration, proliferation, viability, and angiogenesis in vitro were significantly enhanced upon incubation with CM, especially the HPO CM. Experiments in vivo using a rodent model of gastric ulcer demonstrated that HPO CM treatment significantly accelerated wound healing by suppressing inflammation and promoting neovascularization and re-epithelization. Meanwhile, the infusion of HPO CM activated the COX2-PGE2 axis both in vitro and in vivo. And the upregulation of COX2 was further dependent on the activation of ErK1/2-MAPK pathway. In addition, vascular endothelial growth factor, tissue inhibitors of metalloproteinases-1, and chemokine (C-C motif) ligand 20 (CCL-20) were analyzed as being highly abundant factors secreted by ADMSCs under hypoxic condition. Notably, the blockade of CCL-20 abrogated the HPO CM-induced COX2 signaling in the primary gastric mucosal epithelial cells, while incubation with recombinant CCL-20 increased the expression of COX2. In conclusion, the secretome from hypoxia conditioned ADMSCs facilitates the repair of gastric mucosal injury through the enhancement of angiogenesis and re-epithelization, as well as the activation of COX2-PGE2 axis with a paracrine activity involving CCL-20 factor. PMID- 28993191 TI - The anti-aging protein Klotho is induced by GABA therapy and exerts protective and stimulatory effects on pancreatic beta cells. AB - Systemic gamma-aminobutyric acid (GABA) therapy prevents or ameliorates type 1 diabetes (T1D), by suppressing autoimmune responses and stimulating pancreatic beta cells. In beta cells, it increases insulin secretion, prevents apoptosis, and induces regeneration. It is unclear how GABA mediates these effects. We hypothesized that Klotho is involved. It is a multi-functional protein expressed in the kidneys, brain, pancreatic beta cells, other tissues, and is cell-bound or soluble. Klotho knockout mice display accelerated aging, and in humans Klotho circulating levels decline with age, renal disease and diabetes. Here, we report that GABA markedly increased circulating levels of Klotho in streptozotocin (STZ) induced diabetes. GABA also increased Klotho in the islet of Langerhans of normal mice, as well as the islets and kidneys of STZ-treated mice. In vitro, GABA stimulated production and secretion of Klotho by human islet cells. Knockdown (KD) of Klotho with siRNA in INS-1E insulinoma cells abrogated the protective effects of GABA against STZ toxicity. Following KD, soluble Klotho reversed the effects of Klotho deficiency. In human islet cells soluble Klotho protected against cell death, and stimulated proliferation and insulin secretion. NF-kappaB activation triggers beta-cell apoptosis, and both GABA and Klotho suppress this pathway. We found Klotho KD augmented NF-kappaB p65 expression, and abrogated the ability of GABA to block NF-kappaB activation. This is the first report that GABAergic stimulation increases Klotho expression. Klotho protected and stimulated beta cells and lack of Klotho (KD) was reversed by soluble Klotho. These findings have important implications for the treatment of T1D. PMID- 28993192 TI - WITHDRAWN: Up-regulation of RIP3 alleviates cervical cancer progression through inducing necroptosis. AB - This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our business/policies/article-withdrawal. PMID- 28993193 TI - alpha-Lipoic acid inhibits human lung cancer cell proliferation through Grb2 mediated EGFR downregulation. AB - BACKGROUND: Alpha lipoic acid (alpha -LA) is a naturally occurring antioxidant and metabolic enzyme co-factor. Recently, alpha -LA has been reported to inhibit the growth of various cancer cells, but the precise signaling pathways that mediate the effects of alpha -LA on non-small cell lung cancer (NSCLC) development remain unclear. METHODS: The CCK-8 assay was used to assess cell proliferation in NSCLC cell lines after alpha -LA treatment. The expression of growth factor receptor-bound protein 2 (Grb2), cyclin-dependent kinase (CDK)-2, CDK4, CDK6, Cyclin D3, Cyclin E1, Ras, c-Raf, epidermal growth factor receptor (EGFR), ERK1/2 and activated EGFR and ERK1/2 was evaluated by western blotting. Grb2 levels were restored in alpha-LA-treated cells by transfection of a plasmid carrying Grb2 and were reduced in NSCLC cells via specific siRNA-mediated knockdown. RESULTS: alpha -LA dramatically decreased NSCLC cell proliferation by downregulating Grb2; in contrast, Grb2 overexpression significantly prevented alpha-LA-induced decrease in cell growth in vitro. Western blot analysis indicated that alpha-LA decreased the levels of phospho-EGFR, CDK2/4/6, Cyclins D3 and E1, which are associated with the inhibition of G1/S-phase transition. Additional experiments indicated that Grb2 inhibition partially abolished EGF induced phospho-EGFR and phospho-ERK1/2 activity. In addition, alpha-LA exerted greater inhibitory effects than gefitinib on NSCLC cells by preventing EGF induced EGFR activation. CONCLUSION: For the first time, these findings provide the first evidence that alpha-LA inhibits cell proliferation through Grb2 by suppressing EGFR phosphorylation and that MAPK/ERK is involved in this pathway. PMID- 28993194 TI - Identification of a selective inhibitor of human monocarboxylate transporter 4. AB - The human monocarboxylate transporters (hMCTs/SLC16As) mediate the uptake of various monocarboxylates. Several isoforms of hMCTs are expressed in cancerous tissue as well as in normal tissue. In cancerous tissue, hypoxia induces the expression of hMCT4, which transports the energetic metabolite l-lactate across the plasma membrane. Since hMCT4 is involved in pH regulation and the transport of l-lactate in cancer cells, an hMCT4 inhibitor could function as an anticancer agent. Although several non specific hMCT inhibitors have been developed, a selective hMCT4 inhibitor has not yet been identified. The aim of this study was therefore to identify a selective hMCT4 inhibitor for use as a pharmacological tool for studying hMCT4. The heterologous expression system of the Xenopus oocyte was used to assess the effects of test compounds on hMCT4, whereupon isobutyrate derivatives, fibrates, and bindarit (2-[(1-benzyl-1H-indazol-3-yl)methoxy]-2 methylpropanoic acid) were demonstrated to exhibit selective inhibitory effects against this transporter. It is suggested that the structure formed from the joining of an isobutyrate moiety and two aromatic rings by appropriate linkers is important for acquiring the selective hMCT4-inhibiting activity. These findings provide novel insights into the ligand recognition of hMCT4, and contribute to the development of novel anticancer agents. PMID- 28993195 TI - Effect of Trichostatin A on radiation induced epithelial-mesenchymal transition in A549 cells. AB - Radiotherapy is used to treat tumors of different origins and nature, but often lead to development of radioresistance and metastasis of cells. Interestingly, radiation induces epithelial-mesenchymal transition (EMT), a process by which epithelial cells undergo mesenchymal phenotype and stimulates tumor progression capability. Our study investigated the effect of Trichostatin A (TSA), a natural derivate isolated from Streptomyces, upon radiation-induced lung EMT and we tried to understand the role of signaling molecules in irradiated lung cancer cells (A549). The cells were categorized into four groups: untreated control, radiation alone (R; 8Gy, X-ray), radiation combined with TSA (R + T) and TSA (100nM). Radiation-induced lung EMT were evidenced by decreased expression of epithelial marker like E-cadherin, Zona occluden1 (ZO-1) and increased expression of N cadherin and Vimentin. The Snail protein, a master regulator of EMT, was observed to be elevated after radiation treatment. In addition, TGF-beta1 signaling (smad2, 3, and 4) proteins were activated upon irradiation. Western blot data were supported by the altered m-RNA expression of E-cadherin, TGF-beta and Snail genes and this effect were reversed by TSA treatment. In addition to this, as supportive evidence, we performed docking studies between snail protein and TSA using Auto docking software and results suggested that less binding energy was needed for the putative binding of TSA on C-terminal domain of Snail protein. Based on our report, we suggest that TSA can effectively inhibit radiation induced EMT (i) by altering epithelial and mesenchymal markers (ii) by modulating signaling molecules of TGFbeta1 pathway (iii) by inhibiting cancer cell migratory potential in A549 cells (iv)by effectively binding to Snail which is an enhancer of EMT. PMID- 28993196 TI - Long non-coding RNA expression profiles in different severity EV71-infected hand foot and mouth disease patients. AB - Enterovirus 71 (EV71) is associated with the severe hand foot and mouth disease (HFMD) outcomes, however the host-virus interaction mechanism and the pathogenesis remain poorly understood. Long non-coding RNAs (lncRNAs) are involved in variety physiological and pathological processes, but the functions of lncRNAs in EV71 infection remain elusive. Here we profiled the expression of lncRNAs in peripheral blood mononuclear cells (PBMCs) from EV71-infected mild patients, severe patients as well as the healthy controls, and identified 8541 lncRNAs were differentially expressed. Focused on the dynamic changed lncRNAs, we performed systematic bioinformatics analysis with Series Test of Cluster (STC) algorithm, Gene Ontology (GO) analysis, pathway analysis and lncRNA-mRNA co expression network analysis, and revealed the potential functions and related pathways of these lncRNAs were associated with immunity and inflammation during the clinical process of EV71-infected HFMD. Among the significant dynamic changed lncRNAs, ten lncRNAs were screened whose expression were further validated in EV71-infected mild patients, severe patients and healthy control. These results shed light on the potential roles of lncRNAs in EV71-infected HFMD, especially in distinguishing the mild and severe cases for early diagnose and treatment, moreover, provide deeper insight into the mechanism of EV71-induced immune and inflammatory responses, as well as the pathogenesis of the imbalanced inflammation in severe EV71 infection. PMID- 28993197 TI - Increased cellular uptake of peptide-modified PEGylated gold nanoparticles. AB - Gold nanoparticles are promising drug delivery vehicles for nucleic acids, small molecules, and proteins, allowing various modifications on the particle surface. However, the instability and low bioavailability of gold nanoparticles compromise their clinical application. Here, we functionalized gold nanoparticles with CPP fragments (CALNNPFVYLI, CALRRRRRRRR) through sulfhydryl PEG to increase their stability and bioavailability. The resulting gold nanoparticles were characterized with transmission electron microscopy (TEM), dynamic light scattering (DLS), UV-visible spectrometry and X-ray photoelectron spectroscopy (XPS), and the stability in biological solutions was evaluated. Comparing to PEGylated gold nanoparticles, CPP (CALNNPFVYLI, CALRRRRRRRR)-modified gold nanoparticles showed 46 folds increase in cellular uptake in A549 and B16 cell lines, as evidenced by the inductively coupled plasma atomic emission spectroscopy (ICP-AES). The interactions between gold nanoparticles and liposomes indicated CPP-modified gold nanoparticles bind to cell membrane more effectively than PEGylated gold nanoparticles. Surface plasmon resonance (SPR) was used to measure interactions between nanoparticles and the membrane. TEM and uptake inhibitor experiments indicated that the cellular entry of gold nanoparticles was mediated by clathrin and macropinocytosis. Other energy independent endocytosis pathways were also identified. Our work revealed a new strategy to modify gold nanoparticles with CPP and illustrated the cellular uptake pathway of CPP modified gold nanoparticles. PMID- 28993198 TI - Wright-Fisher diffusion bridges. AB - The trajectory of the frequency of an allele which begins at x at time 0 and is known to have frequency z at time T can be modelled by the bridge process of the Wright-Fisher diffusion. Bridges when x=z=0 are particularly interesting because they model the trajectory of the frequency of an allele which appears at a time, then is lost by random drift or mutation after a time T. The coalescent genealogy back in time of a population in a neutral Wright-Fisher diffusion process is well understood. In this paper we obtain a new interpretation of the coalescent genealogy of the population in a bridge from a time t?(0,T). In a bridge with allele frequencies of 0 at times 0 and T the coalescence structure is that the population coalesces in two directions from t to 0 and t to T such that there is just one lineage of the allele under consideration at times 0 and T. The genealogy in Wright-Fisher diffusion bridges with selection is more complex than in the neutral model, but still with the property of the population branching and coalescing in two directions from time t?(0,T). The density of the frequency of an allele at time t is expressed in a way that shows coalescence in the two directions. A new algorithm for exact simulation of a neutral Wright-Fisher bridge is derived. This follows from knowing the density of the frequency in a bridge and exact simulation from the Wright-Fisher diffusion. The genealogy of the neutral Wright-Fisher bridge is also modelled by branching Polya urns, extending a representation in a Wright-Fisher diffusion. This is a new very interesting representation that relates Wright-Fisher bridges to classical urn models in a Bayesian setting. PMID- 28993199 TI - Unraveling the role of hypoxia-inducible factor (HIF)-1alpha and HIF-2alpha in the adaption process of human microvascular endothelial cells (HMEC-1) to hypoxia: Redundant HIF-dependent regulation of macrophage migration inhibitory factor. AB - Hypoxia driven angiogenesis is a prominent feature of tissue regeneration, inflammation and tumor growth and is regulated by hypoxia-inducible factor (HIF) 1 and -2. The distinct functions of HIFs in the hypoxia-induced angiogenesis and metabolic switch of endothelial cells are still unknown and therefore aim of this study. We investigated the role of HIF-1 and -2 in the adaptation of immortalized human microvascular endothelial cells (HMEC-1) to hypoxic conditions (1% O2) in terms of angiogenesis, cytokine secretion, gene expression and ATP/ADP-ratio using shRNA-mediated reduction of the oxygen sensitive alpha-subunits of either HIF-1 or HIF-2 or the combination of both. Reduction of HIF-1alpha diminished cellular energy, hypoxia-induced glycolytic gene expression, and angiogenesis not altering pro-angiogenic factors. Reduction of HIF-2alpha diminished hypoxia induced pro-angiogenic factors, enhanced anti-angiogenic factors and attenuated angiogenesis not altering glycolytic gene expression. Reduction of both HIFs reduced cell survival, gene expression of glycolytic enzymes and pro-angiogenic factors as compared to the corresponding control. Finally, we identified the macrophage migration inhibitory factor (MIF) to be redundantly regulated by HIF-1 and HIF-2 and to be essential in the process of hypoxia-driven angiogenesis. Our results demonstrate a major impact of HIF-1 and HIF-2 on hypoxia-induced angiogenesis indicating distinct but also overlapping functions of HIF-1 and HIF 2. These findings open new possibilities for therapeutic approaches by specifically targeting the HIF-1 and HIF-2 or their target MIF. PMID- 28993200 TI - Pax6 is essential for the generation of late-born retinal neurons and for inhibition of photoreceptor-fate during late stages of retinogenesis. AB - In the developing retina, as in other regions of the CNS, neural progenitors give rise to individual cell types during discrete temporal windows. Pax6 is expressed in retinal progenitor cells (RPCs) throughout the course of retinogenesis, and has been shown to be required during early retinogenesis for generation of most early-born cell types. In this study, we examined the function of Pax6 in postnatal mouse retinal development. We found that Pax6 is essential for the generation of late-born interneurons, while inhibiting photoreceptor differentiation. Generation of bipolar interneurons requires Pax6 expression in RPCs, while Pax6 is required for the generation of glycinergic, but not for GABAergic or non-GABAergic-non-glycinergic (nGnG) amacrine cell subtypes. In contrast, overexpression of either full-length Pax6 or its 5a isoform in RPCs induces formation of cells with nGnG amacrine features, and suppresses generation of other inner retinal cell types. Moreover, overexpression of both Pax6 variants prevents photoreceptor differentiation, most likely by inhibiting Crx expression. Taken together, these data show that Pax6 acts in RPCs to control differentiation of multiple late-born neuronal cell types. PMID- 28993201 TI - Ancient genetic redundancy of eyeless and twin of eyeless in the arthropod ocular segment. AB - Pax6 transcription factors are essential upstream regulators in the developing anterior brain and peripheral visual system of most bilaterian animals. While a single homolog is in charge of these functions in vertebrates, two Pax6 genes are in Drosophila: eyeless (ey) and twin of eyeless (toy). At first glance, their co existence seems sufficiently explained by their differential involvement in the specification of two types of insect visual organs: the lateral compound eyes (ey) and the dorsal ocelli (toy). Less straightforward to understand, however, is their genetic redundancy in promoting defined early and late growth phases of the precursor tissue to these organs: the eye-antennal imaginal disc. Drawing on comparative sequence, expression, and gene function evidence, I here conclude that this gene regulatory network module dates back to the dawn of arthropod evolution, securing the embryonic development of the ocular head segment. Thus, ey and toy constitute a paradigm to explore the organization and functional significance of longterm conserved genetic redundancy of duplicated genes. Indeed, as first steps in this direction, recent studies uncovered the shared use of binding sites in shared enhancers of target genes that are under redundant (string) and, strikingly, even subfunctionalized control by ey and toy (atonal). Equally significant, the evolutionarily recent and paralog-specific function of ey to repress the transcription of the antenna fate regulator Distal-less offers a functionally and phylogenetically well-defined opportunity to study the reconciliation of shared, partitioned, and newly acquired functions in a duplicated developmental gene pair. PMID- 28993202 TI - Temporal expression profiling of plasma proteins reveals oxidative stress in early stages of Type 1 Diabetes progression. AB - : Blood markers other than islet autoantibodies are greatly needed to indicate the pancreatic beta cell destruction process as early as possible, and more accurately reflect the progression of Type 1 Diabetes Mellitus (T1D). To this end, a longitudinal proteomic profiling of human plasma using TMT-10plex-based LC MS/MS analysis was performed to track temporal proteomic changes of T1D patients (n=11) across 9 serial time points, spanning the period of T1D natural progression, in comparison with those of the matching healthy controls (n=10). To our knowledge, the current study represents the largest (>2000 proteins measured) longitudinal expression profiles of human plasma proteome in T1D research. By applying statistical trend analysis on the temporal expression patterns between T1D and controls, and Benjamini-Hochberg procedure for multiple-testing correction, 13 protein groups were regarded as having statistically significant differences during the entire follow-up period. Moreover, 16 protein groups, which play pivotal roles in response to oxidative stress, have consistently abnormal expression trend before seroconversion to islet autoimmunity. Importantly, the expression trends of two key reactive oxygen species-decomposing enzymes, Catalase and Superoxide dismutase were verified independently by ELISA. BIOLOGICAL SIGNIFICANCE: The temporal changes of >2000 plasma proteins (at least quantified in two subjects), spanning the entire period of T1D natural progression were provided to the research community. Oxidative stress related proteins have consistently different dysregulated patterns in T1D group than in age-sex matched healthy controls, even prior to appearance of islet autoantibodies - the earliest sign of islet autoimmunity and pancreatic beta cell stress. PMID- 28993203 TI - Preparation of polysomal fractions from mouse brain synaptoneurosomes and analysis of polysomal-bound mRNAs. AB - BACKGROUND: Here we describe a detailed, reliable protocol for isolation of polysomal fractions from mouse brain synaptoneurosomes. This method is an important tool to study local protein synthesis in neurons. NEW METHOD: We combined rapid preparation of synaptoneurosomes by filtration with polysome profiling. We provide a detailed protocol highlighting difficulties and critical steps of: i) preparation of synaptoneurosomes; ii) polyribosome fractionation from synaptoneurosomes; iii) extraction of proteins and RNA from sucrose gradient fractions. RESULTS: and Comparison with Existing Methods We fractionated polyribosomes from synaptoneurosomes and detected the association of Mmp9, Camk2a and Stx1B mRNA with polysomes in the unstimulated conditions. Synaptic stimulation led to increased levels of Mmp9 and Camk2a mRNA in the heavy polysomal fractions. We compared our protocol with existing methods CONCLUSIONS: We have developed a reliable, effective method to prepare polyribosomal fractions from synaptoneurosomes to study polyribosomal binding of mRNAs as an aspect of synaptic translation in vitro. PMID- 28993205 TI - A novel technology to model pressure-induced cellular injuries in the brain. AB - BACKGROUND: Elevated intracranial pressure (ICP) accompanying a number of neurological emergencies is poorly understood, and lacks a model to determine cellular pathophysiology. This limits our ability to identify cellular and molecular biomarkers associated with the pathological progression from physiologic to pathologic ICP. NEW METHOD: We developed an ex vivo model of pressure-induced brain injury, which combines 3D neural cell cultures and a newly developed Pressure Controlled Cell Culture Incubator (PC3I). Human astrocytes and neurons maintained in 3D peptide-conjugated alginate hydrogels were subjected to pressures that mimic both physiologic and pathologic levels of ICP for up to 48h to evaluate the earliest impacts of isolated pressure on cellular viability and quantify early indicators of pressure-induced cellular injury. RESULTS: Compared to control cell cultures grown under physiologic pressure, sustained pathologic pressure exposure increased the release of intracellular ATP in a cell-specific manner. Eighteen hours of sustained pressure resulted in increased ATP release from neurons but not astrocytes. COMPARISON WITH EXISTING METHODS: Cell culture incubators maintain cultures at normal atmospheric pressure. Based on multiple literature searches, we are not aware of any other cell culture incubator systems that modify the pressure at which primary CNS cells are maintained. CONCLUSION: This model simulates the clinical features of elevated ICP encountered in patients with hydrocephalus, and provides a first estimate of the pathological signaling encountered during the earliest perid of progression in neonatal hydrocephalus. This model should provide a means to better understand the pathological biomarkers associated with the earliest stages of elevated ICP. PMID- 28993206 TI - Targeting receptor tyrosine kinase EphB4 in cancer therapy. AB - Eph receptors and their Eph receptor-interacting (ephrin) ligands together form an important cell communication system with diverse roles. Experimental evidence demonstrated Eph receptor bidirectional signaling with both tumor-suppressing and tumor-promoting activities in cancer cells. The tyrosine kinase EphB4, a member of the Eph receptor family, has been associated with tumor angiogenesis, growth and metastasis, thus making it a valuable and attractive target for drug design for therapeutic applications. In the past decade, many studies have focused on elucidating the structure and function of EphB4 in complex with its ligand ephrinB2 for their role in carcinogenesis. Meanwhile, an array of compounds targeting EphB4 have been studied and several selective inhibitors have been tested in clinical studies. This review discusses the structure and function of the EphB4 receptor, analyzes its potential as a target for anticancer therapy, and summarizes the information about inhibitors of EphB4 kinase activity. Conclusively, EphB4 is a challenging but promising therapeutic target in cancer. PMID- 28993204 TI - A stepwise neuron model fitting procedure designed for recordings with high spatial resolution: Application to layer 5 pyramidal cells. AB - BACKGROUND: Recent progress in electrophysiological and optical methods for neuronal recordings provides vast amounts of high-resolution data. In parallel, the development of computer technology has allowed simulation of ever-larger neuronal circuits. A challenge in taking advantage of these developments is the construction of single-cell and network models in a way that faithfully reproduces neuronal biophysics with subcellular level of details while keeping the simulation costs at an acceptable level. NEW METHOD: In this work, we develop and apply an automated, stepwise method for fitting a neuron model to data with fine spatial resolution, such as that achievable with voltage sensitive dyes (VSDs) and Ca2+ imaging. RESULT: We apply our method to simulated data from layer 5 pyramidal cells (L5PCs) and construct a model with reduced neuronal morphology. We connect the reduced-morphology neurons into a network and validate against simulated data from a high-resolution L5PC network model. COMPARISON WITH EXISTING METHODS: Our approach combines features from several previously applied model-fitting strategies. The reduced-morphology neuron model obtained using our approach reliably reproduces the membrane-potential dynamics across the dendrites as predicted by the full-morphology model. CONCLUSIONS: The network models produced using our method are cost-efficient and predict that interconnected L5PCs are able to amplify delta-range oscillatory inputs across a large range of network sizes and topologies, largely due to the medium after hyperpolarization mediated by the Ca2+-activated SK current. PMID- 28993207 TI - Effects of transcranial direct current stimulation on time limit and ratings of perceived exertion in physically active women. AB - The limiting factors of maximum performance in humans have been extensively investigated. The aim of this study was to verify the acute effects of transcranial direct current stimulation on time limit (i.e., the time by which an individual is able to sustain a certain intensity of effort) at 100% of peak power (tlim@100%PP) and ratings of perceived exertion (RPE). Eleven moderately active women underwent an anthropometric evaluation and a maximal incremental test in the cycle ergometer, in order to obtain peak power (PP). At the two subsequent visits, which were separated by 48-72h, participants were randomly assigned to two experimental conditions: anodal stimulation (a-tDCS) and sham. In the a-tDCS condition, the stimulus was applied in the left dorsolateral prefrontal cortex (DLPFC), with intensity of 2mA for 20min. In the sham condition, the equipment was switched off after 30s of stimulation. Immediately after the conditions, participants performed the tlim@100%PP. Immediately after the tlim@100%PP test, the RPE scale was applied. The results demonstrated that the tlim@100%PP was higher in a-tDCS condition compared to sham condition (p=0.005). No difference was found between the conditions (a-tDCS vs sham) for the RPE (p=0.52). The anodal stimulus increased the tolerance to the exercise performed in the cycloergometer with maximum load, having some ergogenic effect in exercises of cyclic characteristics. PMID- 28993208 TI - Intestinal microbiota impact sepsis associated encephalopathy via the vagus nerve. AB - OBJECTIVE: The pathogenesis of sepsis associated encephalopathy (SAE) remains poorly understood. Vagus nerve plays an important role in gut-microbiota-brain axis. This study aimed to investigate whether vague nerve is a key mediator of the impact of intestinal microbiota on SAE. METHODS: Male rats were randomly divided into four groups (n=20): SHAM (SH) group, lipopolysaccharide (LPS) group, fecal microbiota transplantation (FMT) +LPS group, and vagotomy (VGX)+LPS+FMT group. The left cervical vagotomy was performed 30min before LPS administration in LPS+FMT+VGX group. LPS+ FMT and LPS+FMT+VGX groups received nasogastric infusion of feces from healthy donor three times a day. Fecal samples were collected every two days to monitor changes in microbiota composition by 16S rDNA analysis. Brain function was evaluated by behavioral tests and EEG. The levels of tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, IL-10 in brain cortex were detected by ELISA. The expression of Iba-1 in brain cortex was assessed by immunohistochemistry and Western blot analysis. RESULTS: Significant modification of microbiota composition, characterized by a profound increase of commensals in the Firmicutes phylum and depletion of opportunistic organisms in the Proteobacteria phylum, was observed in FMT groups compared to LPS group. Furthermore, we identified a reconstituted bacterial community enriched in Firmicutes and depleted of Proteobacteria. In both FMT groups the diversity of the fecal microbiota and the microbiota composition were similar to SH group. LPS mice treated with FMT demonstrated a better spatial memory and less EEG abnormalities, significantly attenuated levels of IL-1beta, IL-6, TNF-alpha, and decreased number of Iba-1 positive microglia in the cortex, but these beneficial effects of FMT were reversed by VGX. CONCLUSIONS: FMT can change intestinal microbiota in sepsis patients, and vagus nerve is a key mediator between intestinal microbiota and SAE. These findings suggest that FMT and vagus nerve are potential therapy targets for treating SAE. PMID- 28993209 TI - Rotigotine, a dopamine receptor agonist, increased BDNF protein levels in the rat cortex and hippocampus. AB - Brain-derived neurotrophic factor (BDNF) critically controls the fate and function of the neuronal network and has received much attention as a target of many brain diseases. Dopaminergic system dysfunction has also been implicated in a variety of neuropsychiatric diseases. Rotigotine, a non-ergot dopamine receptor agonist, is used in the treatment of Parkinson's disease and restless legs syndrome. To investigate the effects of rotigotine on neuronal functions both in vivo and in vitro, rats and primary cortical neurons were administered rotigotine, and the mRNA and protein expression levels of BDNF, its receptor TrkB and downstream signaling molecules, and synaptic proteins were determined. We found that BDNF protein was increased in the cortex and hippocampus of rats after 7days of rotigotine treatment. In contrast, BDNF mRNAs were reduced 6h after rotigotine treatment in cultured neurons presumably through the transient suppression of neuronal activity. We identified differential expression of D1, D2, and D3 receptors in the rat brain and cultured neurons. The observed increase in the expression of BDNF protein in the cortex and hippocampus after subchronic administration of rotigotine suggests that it may exert its medical effect in part through improving BDNF function in the brain. In addition, our results highlight the complex relationships between rotigotine and BDNF expression, which depend on the brain region, time course, and dose of the drug. PMID- 28993210 TI - Telomere length, sibling competition and development of antioxidant defense in wild house mice. AB - Antioxidants and telomere length are potential biomarkers for individuals' exposure and ability to cope with environmental stressors. However, intraspecific variations in antioxidant alterations due to natural, life cycle related stress, have been rarely estimated. We investigated those changes in wild-derived house mice in a longitudinal study with natural sibling competition as a stressor. Blood was used for telomere length measurements at 8-weeks age and for several selected antioxidants at 8-weeks and 6-months age. Our results show that most of the antioxidants increase during that time, indicating that antioxidant-system continues to develop after early development and sexual maturation. In addition females had higher antioxidant-levels than males. Mice with longer telomeres had also higher superoxide dismutase-activity and more glutathione than mice with shorter telomeres, meaning that long telomeres are associated with better antioxidant defense at maturation and during later life. Sibling competition at early age affected superoxide dismutase-levels at 6-months, but only in females. Females, which were lighter than the average of the litter had low superoxide dismutase -activity in later adulthood, indicating delayed negative effect of sibling competition on antioxidant defense. Our results highlight that sex and developmental stage are crucial in intraspecific comparisons of the antioxidant status and its alterations. PMID- 28993211 TI - Global cognitive profile and different components of reaction times in obstructive sleep apnea syndrome: Effects of continuous positive airway pressure over time. AB - Obstructive sleep apnea syndrome (OSAS) has been recurrently associated with cognitive and psychomotor impairments. However, the occurrence and possible reversibility of these deficits are still extremely controversial, also as a result of different methodologies adopted used by scholars. The aim of the present study was to compare over time the global cognitive profile of patients with OSAS undergoing the continuous positive airway pressure treatment (CPAP; N=23) with that of patients with OSAS who were not (N=10). A group of healthy participants (N=30) was also included. This study adopted a specific methodological approach allowing the researchers to distinguish between the cognitive and the motor component of reaction times (RTs). After baseline assessment, the same tests were administered after three and six months. No significant differences emerged between groups at each time point. On the other hand, the analysis of cognitive score trajectory over time revealed differences between groups. While healthy controls and OSAS patients undergoing CPAP showed increased MoCA test scores after three months, patients not undergoing CPAP improved their scores only after six months. In addition, patients treated with CPAP also showed significantly faster psychomotor response in motor RTs over time. Results seem to conceivably support a global cognitive vulnerability of non treated OSAS patients. Conversely, the RT response of treated patients can be increased over time by CPAP, at least in the motor component of RTs. Therefore, our study suggests that CPAP may play an important role by slowing down the negative effects of OSAS, and by fostering sufficient cognitive functioning and adequate psychomotor speed. PMID- 28993212 TI - Biocatalytic, one-pot diterminal oxidation and esterification of n-alkanes for production of alpha,omega-diol and alpha,omega-dicarboxylic acid esters. AB - Direct and selective terminal oxidation of medium-chain n-alkanes is a major challenge in chemistry. Efforts to achieve this have so far resulted in low specificity and overoxidized products. Biocatalytic oxidation of medium-chain n alkanes - with for example the alkane monooxygenase AlkB from P. putida GPo1- on the other hand is highly selective. However, it also results in overoxidation. Moreover, diterminal oxidation of medium-chain n-alkanes is inefficient. Hence, alpha,omega-bifunctional monomers are mostly produced from olefins using energy intensive, multi-step processes. By combining biocatalytic oxidation with esterification we drastically increased diterminal oxidation upto 92mol% and reduced overoxidation to 3% for n-hexane. This methodology allowed us to convert medium-chain n-alkanes into alpha,omega-diacetoxyalkanes and esterified alpha,omega-dicarboxylic acids. We achieved this in a one-pot reaction with resting-cell suspensions of genetically engineered Escherichia coli. The combination of terminal oxidation and esterification constitutes a versatile toolbox to produce alpha,omega-bifunctional monomers from n-alkanes. PMID- 28993213 TI - Consumer purchase behaviour of foods with added phytosterols in six European countries: Data from a post-launch monitoring survey. AB - A variety of foods with added phytosterols (plant sterols and stanols, PS) known to lower elevated blood cholesterol is available on the European market. This paper reports findings from a 2015 post-launch monitoring survey on consumer purchase behaviour of foods with added PS in UK, Germany, France, Netherlands, Belgium and Greece. Data from 80,825 households were included. Households were divided into categories depending on number of purchases, household size, age of primary shopper and presence of children <5 years. Penetration rates of households purchasing foods with added PS ranged between 3 and 34%. Of households purchasing PS, 34-61% purchased infrequently (<=2 times/year), 29-36% occasionally (=35 years and <=1% by households with children <5 years. Median PS intakes ranged from 0.11 to 0.30 g/d for all purchasers, from 0.26 to 0.37 g/d for occasional purchasers and from 0.91 to 1.44 g/d for regular purchasers and are hence well below recommended intakes. Intakes exceeding 3 g/d only occurred in 2.5% of purchasing households in UK and Belgium. PMID- 28993214 TI - A comprehensive review on biological properties of citrinin. AB - Citrinin (CIT) is a mycotoxin which causes contamination in the food and is associated with different toxic effects. A web search on CIT has been conducted covering the timespan since 1946. The accumulated data indicate that CIT is produced by several fungal strains belonging to Penicillium, Aspergillus and Monascus genera, and is usually found together with another nephrotoxic mycotoxin, ochratoxin A. Although, it is evident that CIT exposure can exert toxic effects on the heart, liver, kidney, as well as reproductive system, the mechanism of CIT-induced toxicity remains largely elusive. It is still controversial what are the genotoxic and mutagenic effects of CIT. Until now, its toxic effect has been linked to the CIT-mediated oxidative stress and mitochondrial dysfunction in biological systems. However, the toxicity strongly depends on its concentration, route, frequency and time of exposure, as well as from the used test systems. Besides the toxic effects, CIT is also reported to possess a broad spectrum of bioactivities, including antibacterial, antifungal, and potential anticancer and neuro-protective effects in vitro. This systematic review presents the current state of CIT research with emphasis on its bioactivity profile. PMID- 28993216 TI - Atypical Epithelioid Angiomyolipoma: A Rare Variant With Malignant Potential. PMID- 28993215 TI - Surveying selected European feed and livestock production chains for features enabling the case-specific post-market monitoring of livestock for intake and potential health impacts of animal feeds derived from genetically modified crops. AB - This review, which has been prepared within the frame of the European Union (EU) funded project MARLON, surveys the organisation and characteristics of specific livestock and feed production chains (conventional, organic, GM-free) within the EU, with an emphasis on controls, regulations, traceability, and common production practices. Furthermore, an overview of the origin of animal feed used in the EU as well as an examination of the use of genetically modified organisms (GMOs) in feed is provided. From the data, it shows that livestock is traceable at the herd or individual level, depending on the species. Husbandry practices can vary widely according to geography and animal species, whilst controls and checks are in place for notifiable diseases and general health symptoms (such as mortality, disease, productive performance). For feeds, it would be possible only to make coarse estimates, at best, for the amount of GM feed ingredients that an animal is exposed to. Labeling requirements are apparently correctly followed. Provided that confounding factors are taken into account, practices such as organic agriculture that explicitly involve the use of non-GM feeds could be used for comparison to those involving the use of GM feed. PMID- 28993218 TI - Novel therapeutic targets in diabetic macular edema: Beyond VEGF. AB - The leading cause of major vision loss in diabetic persons is diabetic macular edema (DME). The hallmark feature of diabetic retinopathy is the alteration of the blood-retinal barrier (BRB). Inflammation plays a crucial role in DME with involvement of several chemokines and cytokines including vascular endothelial growth factor (VEGF). VEGF is a potent cytokine and vaso-permeability factor that has been targeted in multiple, large clinical trials. Multiple anti-VEGF drugs are widely used in the treatment of diabetic macular edema (DME) as the first line of treatment, and have been shown to be effective in vision improvement and prevention of vision loss. However, many DME patients do not show complete response to anti-VEGF drugs despite multiple intravitreal injections with these drugs. Also, the effect seems to be transient in those responders, and many patients do not show complete resolution of fluid. This article summarizes the mechanisms other than VEGF, and how these novel factors can be targeted as promising therapies of DME. PMID- 28993217 TI - Mechanistic Physiologically Based Pharmacokinetic Modeling of the Dissolution and Food Effect of a Biopharmaceutics Classification System IV Compound-The Venetoclax Story. AB - Venetoclax, a selective B-cell lymphoma-2 inhibitor, is a biopharmaceutics classification system class IV compound. The aim of this study was to develop a physiologically based pharmacokinetic (PBPK) model to mechanistically describe absorption and disposition of an amorphous solid dispersion formulation of venetoclax in humans. A mechanistic PBPK model was developed incorporating measured amorphous solubility, dissolution, metabolism, and plasma protein binding. A middle-out approach was used to define permeability. Model predictions of oral venetoclax pharmacokinetics were verified against clinical studies of fed and fasted healthy volunteers, and clinical drug interaction studies with strong CYP3A inhibitor (ketoconazole) and inducer (rifampicin). Model verification demonstrated accurate prediction of the observed food effect following a low-fat diet. Ratios of predicted versus observed Cmax and area under the curve of venetoclax were within 0.8- to 1.25-fold of observed ratios for strong CYP3A inhibitor and inducer interactions, indicating that the venetoclax elimination pathway was correctly specified. The verified venetoclax PBPK model is one of the first examples mechanistically capturing absorption, food effect, and exposure of an amorphous solid dispersion formulated compound. This model allows evaluation of untested drug-drug interactions, especially those primarily occurring in the intestine, and paves the way for future modeling of biopharmaceutics classification system IV compounds. PMID- 28993219 TI - Involvement of posterior cingulate cortex in ketamine-induced psychosis relevant behaviors in rats. AB - The involvement of posterior cingulate cortex (PCC) on ketamine-induced psychosis relevant behaviors was investigated in rats. Bilateral infusion of muscimol, a GABAA receptor agonist, into the PCC significantly antagonized ketamine-induced deficit in prepulse inhibition of a startle reflex (PPI), deficit in gating of hippocampal auditory evoked potentials, and behavioral hyperlocomotion in a dose dependent manner. Local infusion of ketamine directly into the PCC also induced a PPI deficit. Systemic injection of ketamine (3mg/kg,s.c.) induced an increase in power of electrographic activity in the gamma band (30-100Hz) in both the PCC and the hippocampus; peak theta (4-10Hz) power was not significantly altered, but peak theta frequency was increased by ketamine. In order to exclude volume conduction from the hippocampus to PCC, inactivation of the hippocampus was made by local infusion of muscimol into the hippocampus prior to ketamine administration. Muscimol in the hippocampus effectively blocked ketamine-induced increase of gamma power in the hippocampus but not in the PCC, suggesting independent generation of gamma waves in PCC and hippocampus. It is suggested that the PCC is part of the brain network mediating ketamine-induced psychosis related behaviors. PMID- 28993220 TI - Silk fibroin/hydroxyapatite composites for bone tissue engineering. AB - Silk fibroin (SF) is a natural fibrous polymer with strong potential for many biomedical applications. SF has attracted interest in the field of bone tissue engineering due to its extraordinary characteristics in terms of elasticity, flexibility, biocompatibility and biodegradability. However, low osteogenic capacity has limited applications for SF in the orthopedic arena unless suitably functionalized. Hydroxyapatite (HAp) is a well-established bioceramic with biocompatibility and appropriate for constructing orthopedic and dental substitutes. However, HAp ceramics tend to be brittle which can restrict applications in the repair of load-bearing tissues such as bones. Therefore, blending SF and HAp combines the useful properties of both materials as bone constructs for tissue engineering, the subject of this review. PMID- 28993221 TI - Recent advances in polysaccharide bio-based flocculants. AB - Natural polysaccharides, derived from biomass feedstocks, marine resources, and microorganisms, have been attracting considerable attention as benign and environmentally friendly substitutes for synthetic polymeric products. Besides many other applications, these biopolymers are rapidly emerging as viable alternatives to harmful synthetic flocculating agents for the removal of contaminants from water and wastewater. In recent years, a great deal of effort has been devoted to improve the production and performance of polysaccharide bio based flocculants. In this review, current trends in preparation and chemical modification of polysaccharide bio-based flocculants and their flocculation performance are discussed. Aspects including mechanisms of flocculation, biosynthesis, classification, purification and characterization, chemical modification, the effect of physicochemical factors on flocculating activity, and recent applications of polysaccharide bio-based flocculants are summarized and presented. PMID- 28993222 TI - The Chikungunya epidemic in the Caribbean did not impact tourism. PMID- 28993223 TI - International travelers with infectious diseases determined by pathology results, Centers for Disease Control and Prevention - United States, 1995-2015. AB - BACKGROUND: The failure to consider travel-related diagnoses, the lack of diagnostic capacity for specialized laboratory testing, and the declining number of autopsies may affect the diagnosis and management of travel-related infections. Pre- and post-mortem pathology can help determine causes of illness and death in international travelers. METHODS: We conducted a retrospective review of biopsy and autopsy specimens sent to the Infectious Diseases Pathology Branch laboratory (IDPBL) at the Centers for Disease Control and Prevention (CDC) for diagnostic testing from 1995 through 2015. Cases were included if the specimen submitted for diagnosis was from a traveler with prior international travel during the disease incubation period and the cause of illness or death was unknown at the time of specimen submission. RESULTS: Twenty-one travelers, six (29%) with biopsy specimens and 15 (71%) with autopsy specimens, met the inclusion criteria. Among the 15 travelers who underwent autopsies, the most common diagnoses were protozoal infections (7 travelers; 47%), including five malaria cases, followed by viral infections (6 travelers; 40%). CONCLUSIONS: Biopsy or autopsy specimens can assist in diagnosing infectious diseases in travelers, especially from pathogens not endemic in the U.S. CDC's IDPBL provides a useful resource for clinicians considering infectious diseases in returned travelers. PMID- 28993224 TI - Differences between observed and estimated by hematocrit hemoglobin and its implications in the diagnosis of anemia: Analysis of data derived from the PERU MIGRANT study (PEru's rural to urban MIGRANTs study). PMID- 28993225 TI - Treatment Approach and Prognosis of Pediatric and Adolescent Nonepithelial Malignant Ovarian Tumors: A Retrospective Prognosis Analysis. AB - STUDY OBJECTIVE: Nonepithelial malignant ovarian tumors are rare in the pediatric and adolescent population. The aim of this study was to observe the spectrum of pathology, presentation, outcome, and risk factors for survival of pediatric nonepithelial malignant ovarian tumors in a Chinese pediatric population. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: This was a retrospective study of 171 girls (median age at presentation of 14 years) diagnosed with primary malignant ovarian tumors between 1990 and 2014 at the Yat Sen Memorial Hospital and Cancer Center of Sun Yat-sen University. Symptoms, pathological data, treatments, and outcomes were obtained retrospectively from the medical records. RESULTS: Most (85.96%, 147/171) tumors occurred in patients aged 10-18 years and most cases were International Federation of Gynecology and Obstetrics stage I (68.42%, 117/171). The predominant pathological type was germ cell tumors (87.13%, 149/171). All patients underwent surgery, and 87 (50.88%, 87/171) underwent conservative incomplete staging surgery (unilateral salpingo oophorectomy or tumor excision). The 5-year progression-free survival (PFS) was 59.2%. The 5-year overall survival (OS) was 88.7%. Surgical hospital (hazard ratio, 0.388; 95% confidence interval, 0.213-0.706; P = .002) was independently associated with PFS. Recurrence state (hazard ratio, 163.26; 95% confidence interval, 1.321-20,181.875; P = .038) was independently associated with OS. CONCLUSION: Ovarian cancers in children and adolescents have features of good prognosis. Girls who received their first surgery in a tertiary hospital had better PFS. Patients who did not suffer recurrence had better OS. PMID- 28993226 TI - Vulvar Lesions in an 8-Year-Old Girl: Cutaneous Manifestations of Multisystem Langerhans Cell Histiocytosis. AB - BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare localized or systemic disease characterized by proliferation of myeloid-derived dendritic cells. Vulvar lesions might be the herald symptom of LCH and might mimic other cutaneous lesions. Prognosis varies widely on the basis of the extent and spread of disease. CASE: An 8-year-old girl with a 4-month history of vulvar lesions resistant to topical steroids was referred by her pediatrician. Vulvar biopsy was diagnostic for LCH. Imaging studies revealed a left hip lesion consistent with LCH. The patient was subsequently treated for multisystem LCH with vinblastine and prednisone. SUMMARY AND CONCLUSION: Although rare, LCH might be diagnosed by gynecologic providers and should be included in the differential diagnosis of genital lesions. We recommend having a low threshold for performing biopsy of vulvar lesions. PMID- 28993227 TI - Adverse glycaemic effects of cancer therapy: indications for a rational approach to cancer patients with diabetes. AB - Diabetes and cancer are common, chronic, and potentially fatal diseases that frequently co-exist. Observational studies have reported an increased risk of cancer in patients with diabetes. Furthermore, many patients with cancer already have diabetes, or develop hyperglycaemia as a consequence of the tumor or of cancer therapies, and coexisting diabetes confers a greater risk of mortality for many malignancies. Managing oncologic patients with diabetes is often complicated, since the co-existence of diabetes and cancer poses several complex clinical questions: what level of glycaemic control to achieve, which therapy to use, how to deal with glucocorticoid therapies and artificial nutrition, how diabetes complications can affect cancer management, which drug-drug interactions should be taken into account, or even how to manage diabetes at the end of life. In the clinical setting, both at hospital and at home, there are little agreed, evidence-based guidelines on the best management and criteria upon which clinical decisions should be based. A practical solution lies in the implementation of care networks based on communication and ongoing collaboration between Oncologists, Endocrinologists, and the nursing staff, with the patient at the centre of the care process. This manuscript aims to review the current evidence on the effect of cancer therapies on glucose metabolism and to address some of the more common challenges of diabetes treatment in patients with cancer. PMID- 28993229 TI - Combating flu in China. AB - China is a major source of avian influenza viruses (AIVs) with bird-to-human transmissibility. Thus, understanding these viruses and treating infections at their source should decrease spread of AIVs to other countries in the world. This special issue focuses on the molecular epidemiology and pathogenesis of influenza viruses, and provides results on current efforts to develop vaccines against AIVs. PMID- 28993230 TI - The importance of blood platelet lipid signaling in thrombosis and in sepsis. AB - Blood platelets are the first line of defense against hemorrhages and are also strongly involved in the processes of arterial thrombosis, a leading cause of death worldwide. Besides their well-established roles in hemostasis, vascular wall repair and thrombosis, platelets are now recognized as important players in other processes such as inflammation, healing, lymphangiogenesis, neoangiogenesis or cancer. Evidence is accumulating they are key effector cells in immune and inflammatory responses to host infection. To perform their different functions platelets express a wide variety of membrane receptors triggering specific intracellular signaling pathways and largely use lipid signaling systems. Lipid metabolism is highly active in stimulated platelets including the phosphoinositide metabolism with the phospholipase C (PLC) and the phosphoinositide 3-kinase (PI3K) pathways but also other enzymatic systems producing phosphatidic acid, lysophosphatidic acid, platelet activating factor, sphingosine 1-phosphate and a number of eicosanoids. While several of these bioactive lipids regulate intracellular platelet signaling mechanisms others are released by activated platelets acting as autocrine and/or paracrine factors modulating neighboring cells such as endothelial and immune cells. These bioactive lipids have been shown to play important roles in hemostasis and thrombosis but also in vessel integrity and dynamics, inflammation, tissue remodeling and wound healing. In this review, we will discuss some important aspects of platelet lipid signaling in thrombosis and during sepsis that is an important cause of death in intensive care unit. We will particularly focus on the implication of the different isoforms of PI3Ks and on the generation of eicosanoids released by activated platelets. PMID- 28993228 TI - Kinase-independent role of nuclear RIPK1 in regulating parthanatos through physical interaction with PARP1 upon oxidative stress. AB - Regulated necrosis occurs in various pathophysiological conditions under oxidative stress. Here, we report that receptor-interacting protein kinase 1 (RIPK1), a key player in one type of regulated necrosis (necroptosis), also participates in another type of poly (ADP-ribose) polymerase 1 (PARP1)-dependent regulated necrosis (parthanatos). Various biological signatures of parthanatos were significantly attenuated in Ripk1-/- mouse embryonic fibroblasts, including PARylation, nuclear translocation of apoptosis-inducing factor, and PARP1 dependent cell death under H2O2 exposure. Hence, we investigated whether RIPK1 regulates the activity of PARP1. RIPK1 activated PARP1 via an interaction with the catalytic domain of PARP1 in the nucleus. Of note, both wild type and kinase dead mutant RIPK1 induced PARP1 activation and led to PARP1-mediated cell death upon H2O2 insult, demonstrating the kinase-independent regulation of RIPK1 in PARP1 activation. Collectively, our results demonstrate the existence of a kinase independent role of nuclear RIPK1 in the regulation of PARP1. PMID- 28993231 TI - Decoding spoken phonemes from sensorimotor cortex with high-density ECoG grids. AB - For people who cannot communicate due to severe paralysis or involuntary movements, technology that decodes intended speech from the brain may offer an alternative means of communication. If decoding proves to be feasible, intracranial Brain-Computer Interface systems can be developed which are designed to translate decoded speech into computer generated speech or to instructions for controlling assistive devices. Recent advances suggest that such decoding may be feasible from sensorimotor cortex, but it is not clear how this challenge can be approached best. One approach is to identify and discriminate elements of spoken language, such as phonemes. We investigated feasibility of decoding four spoken phonemes from the sensorimotor face area, using electrocorticographic signals obtained with high-density electrode grids. Several decoding algorithms including spatiotemporal matched filters, spatial matched filters and support vector machines were compared. Phonemes could be classified correctly at a level of over 75% with spatiotemporal matched filters. Support Vector machine analysis reached a similar level, but spatial matched filters yielded significantly lower scores. The most informative electrodes were clustered along the central sulcus. Highest scores were achieved from time windows centered around voice onset time, but a 500 ms window before onset time could also be classified significantly. The results suggest that phoneme production involves a sequence of robust and reproducible activity patterns on the cortical surface. Importantly, decoding requires inclusion of temporal information to capture the rapid shifts of robust patterns associated with articulator muscle group contraction during production of a phoneme. The high classification scores are likely to be enabled by the use of high density grids, and by the use of discrete phonemes. Implications for use in Brain-Computer Interfaces are discussed. PMID- 28993232 TI - MR elastography of the brain and its application in neurological diseases. AB - Magnetic resonance elastography (MRE) is an imaging technique for noninvasively and quantitatively assessing tissue stiffness, akin to palpation. MRE is further able assess the mechanical properties of tissues that cannot be reached by hand including the brain. The technique is a three-step process beginning with the introduction of shear waves into the tissue of interest by applying an external vibration. Next, the resulting motion is imaged using a phase-contrast MR pulse sequence with motion encoding gradients that are synchronized to the vibration. Finally, the measured displacement images are mathematically inverted to compute a map of the estimated stiffness. In the brain, the technique has demonstrated strong test-retest repeatability with typical errors of 1% for measuring global stiffness, 2% for measuring stiffness in the lobes of the brain, and 3-7% for measuring stiffness in subcortical gray matter. In healthy volunteers, multiple studies have confirmed that stiffness decreases with age, while more recent studies have demonstrated a strong relationship between viscoelasticity and behavioral performance. Furthermore, several studies have demonstrated the sensitivity of brain stiffness to neurodegeneration, as stiffness has been shown to decrease in multiple sclerosis and in several forms of dementia. Moreover, the spatial pattern of stiffness changes varies among these different classes of dementia. Finally, MRE is a promising tool for the preoperative assessment of intracranial tumors, as it can measure both tumor consistency and adherence to surrounding tissues. These factors are important predictors of surgical difficulty. In brief, MRE demonstrates potential value in a number of neurological diseases. However, significant opportunity remains to further refine the technique and better understand the underlying physiology. PMID- 28993234 TI - Epidemiology of hyperhidrosis in 2 population-based health care databases. AB - BACKGROUND: Population-based and clinical case reports of hyperhidrosis (HH) provide prevalence estimates that vary widely across reported studies because of differences in case ascertainment. OBJECTIVE: In this study, we specify diagnostic, symptom, and prescription codes for HH to estimate incidence and prevalence for the United Kingdom and the United States. METHODS: Data from UK and US health care databases were analyzed to ascertain HH cases and estimate incidence and prevalence from health care records during calendar years 2011 through 2013. RESULTS: On the basis of 2013 data for the United States and United Kingdom, between 1.0% and 1.6% of these populations have health care records indicating diagnosis or treatment of HH. Women accounted for approximately 60% of incident and prevalent cases in both databases. LIMITATIONS: Because the case ascertainment methods rely on available data for those seeking health care, we may have underestimated the number of HH cases in both countries. CONCLUSIONS: The findings represent a plausible estimate for incidence and prevalence of HH among persons seeking medical care for excessive sweating. Improved practices for identifying HH in clinical settings may increase the sensitivity and specificity of future studies and improve characterization and quantification of the population burden of this significant disease. PMID- 28993233 TI - The distribution of the alpha7 nicotinic acetylcholine receptor in healthy aging: An in vivo positron emission tomography study with [18F]ASEM. AB - : Altered function of the alpha7 nicotinic acetylcholine receptor (alpha7-nAChR) is implicated in several neuropsychiatric diseases. Nevertheless, studies of the human cerebral alpha7-nAChR even in healthy aging are limited in number and to postmortem tissue. METHODS: The distribution of the cerebral alpha7-nAChR was estimated in nine brain regions in 25 healthy volunteers (ages 21-86 years; median 57 years, interquartile range 52 years) using [18F]ASEM with positron emission tomography (PET) imaging. Regional total distribution volume (VT) measurements were calculated using the Logan method from each subject's 90 min dynamic PET data and their metabolite-corrected plasma input function. Spearman's rank or Pearson's correlation analysis was used depending on the normality of the data. Correlation between age and regional 1) volume relative to intracranial volume (volume ratio) and 2) [18F]ASEM VT was tested. Correlation between regional volume ratio and [18F]ASEM VT was also evaluated. Finally, the relationship between [18F]ASEM VT and neuropsychological measures was investigated in a subpopulation of 15 elderly healthy participants (those 50 years of age and older). Bonferroni correction for multiple comparisons was applied to statistical analyses. RESULTS: A negative correlation between tissue volume ratio and age was observed in six of the nine brain regions including striatum and five cortical (temporal, occipital, cingulate, frontal, or parietal) regions. A positive correlation between [18F]ASEM VT and age was observed in all nine brain regions of interest (ROIs). There was no correlation between [18F]ASEM VT and volume ratio in any ROI after controlling for age. Regional [18F]ASEM VT and neuropsychological performance on each of eight representative subtests were not correlated among the well-performing subpopulation of elderly healthy participants. CONCLUSIONS: Our results suggest an increase in cerebral alpha7 nAChR distribution over the course of healthy aging that should be tested in future longitudinal studies. The preservation of the alpha7-nAChR in the aging human brain supports the development of therapeutic agents that target this receptor for use in the elderly. Further study of the relationship between alpha7 nAChR availability and cognitive impairment over aging is needed. PMID- 28993235 TI - Wood's lamp as a tool in the evaluation of morphea. PMID- 28993236 TI - Affective blindsight relies on low spatial frequencies. AB - The human brain can process facial expressions of emotions rapidly and without awareness. Several studies in patients with damage to their primary visual cortices have shown that they may be able to guess the emotional expression on a face despite their cortical blindness. This non-conscious processing, called affective blindsight, may arise through an intact subcortical visual route that leads from the superior colliculus to the pulvinar, and thence to the amygdala. This pathway is thought to process the crude visual information conveyed by the low spatial frequencies of the stimuli. In order to investigate whether this is the case, we studied a patient (TN) with bilateral cortical blindness and affective blindsight. An fMRI paradigm was performed in which fearful and neutral expressions were presented using faces that were either unfiltered, or filtered to remove high or low spatial frequencies. Unfiltered fearful faces produced right amygdala activation although the patient was unaware of the presence of the stimuli. More importantly, the low spatial frequency components of fearful faces continued to produce right amygdala activity while the high spatial frequency components did not. Our findings thus confirm that the visual information present in the low spatial frequencies is sufficient to produce affective blindsight, further suggesting that its existence could rely on the subcortical colliculo pulvino-amygdalar pathway. PMID- 28993237 TI - Sonic hedgehog induces GLT-1 degradation via PKC delta to suppress its transporter activities. AB - GLT-1 is mainly expressed in astrocytes and has a crucial role in glutamate uptake. Sonic hedgehog (SHH) can inhibit glutamate uptake and its pathway is activated in many brain diseases related with glutamate excitotoxicity. However, whether SHH regulates GLT-1 to affect glutamate uptake is not clear. Here, we use pharmacological and genetic methods to show that SHH induces GLT-1 degradation in astrocytes in a manner that is dependent on PKC delta (PKCdelta) to regulate GLT 1 activities. GLT-1 protein levels are reduced as early as 2 hs in astrocytes after incubation with SHH, whereas its mRNA levels are not changed. This reduction is recapitulated when astrocytes are transfected with SmoA1, a constitutively active form of Smoothened (Smo), the mediator of SHH pathway. The reduction of GLT-1 and inhibition of aspartate current are not observed when staurosporine (STP) and BisindolylmaleimideII (BisII), agents known as PKC inhibitors, are present. Further, when PKCdelta is knocked down in astrocytes, SHH cannot reduce GLT-1 protein levels. Therefore, SHH induces degradation of GLT 1 through PKCdelta to regulate its activities. PMID- 28993238 TI - Thalamo-insular pathway conveying orofacial muscle proprioception in the rat. AB - Little is known about how proprioceptive signals arising from muscles reach to higher brain regions such as the cerebral cortex. We have recently shown that a particular thalamic region, the caudo-ventromedial edge (VPMcvm) of ventral posteromedial thalamic nucleus (VPM), receives the proprioceptive signals from jaw-closing muscle spindles (JCMSs) in rats. In this study, we further addressed how the orofacial thalamic inputs from the JCMSs were transmitted from the thalamus (VPMcvm) to the cerebral cortex in rats. Injections of a retrograde and anterograde neuronal tracer, wheat-germ agglutinin-conjugated horseradish peroxidase (WGA-HRP), into the VPMcvm demonstrated that the thalamic pathway terminated mainly in a rostrocaudally narrow area in the dorsal part of granular insular cortex rostroventrally adjacent to the rostralmost part of the secondary somatosensory cortex (dGIrvs2). We also electrophysiologically confirmed that the dGIrvs2 received the proprioceptive inputs from JCMSs. To support the anatomical evidence of the VPMcvm-dGIrvs2 pathway, injections of a retrograde neuronal tracer Fluorogold into the dGIrvs2 demonstrated that the thalamic neurons projecting to the dGIrvs2 were confined in the VPMcvm and the parvicellular part of ventral posterior nucleus. In contrast, WGA-HRP injections into the lingual nerve area of core VPM demonstrated that axon terminals were mainly labeled in the core regions of the primary and secondary somatosensory cortices, which were far from the dGIrvs2. These results suggest that the dGIrvs2 is a specialized cortical region receiving the orofacial proprioceptive inputs. Functional contribution of the revealed JCMSs-VPMcvm-dGIrvs2 pathway to Tourette syndrome is also discussed. PMID- 28993239 TI - Regulation of NADPH oxidase NOX4 by delta iodolactone (IL-delta) in thyroid cancer cells. AB - INTRODUCTION: Iodine is not used only by the thyroid to synthesize thyroid hormones but also directly influences a number of thyroid parameters such as thyroid proliferation and function. Several iodinated lipids, biosynthesized by the thyroid, were postulated as intermediaries in the action of iodide. Among these, iodolactone (IL-delta) and 2-iodohexadecanal (2-IHDA) have shown to inhibit several thyroid parameters. The antiproliferative effect of IL-delta is not restricted to the thyroid gland. IL-delta exhibits anti-tumor properties in breast cancer, neuroblastoma, glioblastoma, melanoma and lung carcinoma cells suggesting that IL-delta could be used as a chemotherapeutic agent. Moreover in a colon cancer cell line (HT-29), IL-delta induced cell death, and this effect was mediated by reactive oxygen species (ROS) generation. The aim of the present study was to analyze the sources of reactive oxygen species induced by IL-delta and to explore the contribution of ROS induced by IL-delta on cell proliferation and apoptosis. METHODOLOGY AND RESULTS: Cancer thyroid follicular (WRO) and papilar (TPC-1) cells lines were treated with IL-delta. Proliferation and apoptosis was analyzed. IL-delta caused a significant loss of cell viability on WRO and TPC-1 cells in a concentration dependent manner and induced apoptosis after 3 h of treatment. Furthermore, IL-delta (10 MUM) increased ROS production (39% WRO and 20% TPC-1). The concomitant treatment of WRO and TPC-1 cells with Trolox or NAC plus IL-delta abrogated the augment of ROS induced by IL-delta exposure. Additionally Trolox and NAC reversed the effect of IL-delta on cell proliferation and apoptosis. Only in WRO cells IL-delta upregulates NADPH oxidase NOX4 expression, and siRNA targeted knock-down of NOX4 attenuates ROS production, apoptosis (p < 0.05) and the inhibitory effect of IL-delta on cell proliferation and PCNA expression (p < 0.05). CONCLUSIONS: The antiproliferative and pro apoptotic effect of IL-delta is mediated by different mechanisms and pathway involving different sources of ROS generation depending on the cellular context. PMID- 28993240 TI - The oximes HI-6 and MMB-4 fail to reactivate soman-inhibited human and guinea pig AChE: A kinetic in vitro study. AB - Acetylcholinesterase (AChE) inhibited by the organophosphorus nerve (OP) agent soman underlies a spontaneous and extremely rapid dealkylation ("aging") reaction which prevents reactivation by oximes. However, in vivo studies in various, soman poisoned animal species showed a therapeutic effect of oximes, with the exact mechanism of this effect remaining still unclear. In order to get more insight and a basis for the extrapolation of animal data to humans, we applied a dynamic in vitro model with continuous online determination of AChE activity. This model allows to simulate the in vivo toxico- and pharmacokinetics between human and guinea pig AChE with soman and the oximes HI-6 and MMB-4 in order to unravel the species dependent kinetic interactions. It turned out that only HI-6 was able to slow down the ongoing inhibition of human AChE by soman without preventing final complete inhibition of the enzyme. Continuous perfusion of AChE with soman and simultaneous or delayed (8, 15 or 40min) oxime perfusion did not result in a relevant reactivation of AChE (less than 2%). In conclusion, the results of the present study indicate a negligible reactivation of soman-inhibited AChE by oximes at conditions simulating the in vivo poisoning by soman. The observed therapeutic effect of oximes in soman poisoned animals in vivo must be attributed to alternative mechanisms which may not be relevant in humans. PMID- 28993241 TI - Discoid Resection of Rectosigmoid Endometriotic Nodules. AB - STUDY OBJECTIVE: To show various techniques to perform laparoscopic anterior discoid resection of rectosigmoid endometriotic nodules. DESIGN: A step-by-step explanation of the techniques using video with narration (educational video). SETTING: Segmental bowel resection and reanastomosis are treatment options for larger rectosigmoid endometriotic nodules. However, laparoscopic anterior discoid resection of rectosigmoid endometriotic nodules is feasible and potentially less morbid in the appropriate candidate. Detailed knowledge of the avascular planes of the pelvis, particularly the pararectal and rectovaginal spaces, is crucial when approaching these nodules, which may initially present within an obliterated posterior cul-de-sac. Resection begins with determination of the nodule size followed by enucleation of the nodule itself. A 2-layer closure with barbed suture is then performed using a rectal probe as a template. Our institution previously demonstrated that barbed suture is safe to use in bowel repair and did not result in major complications [1]. An air leak test assesses the integrity of the repair and may be completed with air insufflation or with a methylene blue or povidone-iodine enema. With larger nodules, a V-shaped closure may be necessary. The patients provided consent to use images and videos of the procedure. Institutional review board approval was not required for this procedure. INTERVENTIONS: Laparoscopic anterior discoid resection of a rectosigmoid endometriotic nodule. CONCLUSION: Laparoscopic anterior discoid resection avoids the need for segmental bowel resection and reanastomosis. Barbed suture is a safe option for 2-layer bowel closure [1]. PMID- 28993242 TI - A distinct microRNA expression profile is associated with alpha[11C]-methyl-L tryptophan (AMT) PET uptake in epileptogenic cortical tubers resected from patients with tuberous sclerosis complex. AB - Tuberous sclerosis complex (TSC) is characterized by hamartomatous lesions in various organs and arises due to mutations in the TSC1 or TSC2 genes. TSC mutations lead to a range of neurological manifestations including epilepsy, cognitive impairment, autism spectrum disorders (ASD), and brain lesions that include cortical tubers. There is evidence that seizures arise at or near cortical tubers, but it is unknown why some tubers are epileptogenic while others are not. We have previously reported increased tryptophan metabolism measured with alpha[11C]-methyl-l-tryptophan (AMT) positron emission tomography (PET) in epileptogenic tubers in approximately two-thirds of patients with tuberous sclerosis and intractable epilepsy. However, the underlying mechanisms leading to seizure onset in TSC remain poorly characterized. MicroRNAs are enriched in the brain and play important roles in neurodevelopment and brain function. Recent reports have shown aberrant microRNA expression in epilepsy and TSC. In this study, we performed microRNA expression profiling in brain specimens obtained from TSC patients undergoing epilepsy surgery for intractable epilepsy. Typically, in these resections several non-seizure onset tubers are resected together with the seizure-onset tubers because of their proximity. We directly compared seizure onset tubers, with and without increased tryptophan metabolism measured with PET, and non-onset tubers to assess the role of microRNAs in epileptogenesis associated with these lesions. Whether a particular tuber was epileptogenic or non-epileptogenic was determined with intracranial electrocorticography, and tryptophan metabolism was measured with AMT PET. We identified a set of five microRNAs (miR-142-3p, 142-5p, 223-3p, 200b-3p and 32 5p) that collectively distinguish among the three primary groups of tubers: non onset/AMT-cold (NC), onset/AMT-cold (OC), and onset/AMT-hot (OH). These microRNAs were significantly upregulated in OH tubers compared to the other two groups, and microRNA expression was most significantly associated with AMT-PET uptake. The microRNAs target a group of genes enriched for synaptic signaling and epilepsy risk, including SLC12A5, SYT1, GRIN2A, GRIN2B, KCNB1, SCN2A, TSC1, and MEF2C. We confirmed the interaction between miR-32-5p and SLC12A5 using a luciferase reporter assay. Our findings provide a new avenue for subsequent mechanistic studies of tuber epileptogenesis in TSC. PMID- 28993245 TI - Testing a cue outside the training context increases attention to the contexts and impairs performance in human predictive learning. AB - One experiment in human predictive learning explored the impact of a context change on attention to contexts and predictive ratings controlled by the cue. In Context A: cue X was paired with an outcome four times, while cue Y was presented without an outcome four times in Context B:. In both contexts filler cues were presented without the outcome. During the test, target cues X and Y were presented either in the context where they were trained, or in the alternative context. With the context change expectation of the outcome X, expressed as predictive ratings, decreased in the presence of X and increased in the presence of Y. Looking at the contexts, expressed as a percentage of the overall gaze dwell time on a trial, was high across the four training trials, and increased with the context change. Results suggest that the presentation of unexpected information leads to increases in attention to contextual cues. Implications for contextual control of behavior are discussed. PMID- 28993244 TI - Effects of reinforcement value on instruction following under schedules of negative reinforcement. AB - The effects of reinforcement value and social control on instruction following under a negative-reinforcement (escape) schedule were studied. Initially, responding produced timeouts from pressing a force cell under a low and a high force requirement on a fixed-ratio 1 schedule of reinforcement. Next, participants were reexposed to the low and high force requirements, but were instructed that the experimenter expected them to decrease the number of timeouts relative to the previous exposures to the procedure. Even though following the instruction led to a decrease in number of timeouts and to an increase in effort (i.e., was non-efficient), instruction following occurred consistently for each participant and was modulated by reinforcement value. That is, the decrease in the number of timeouts (i.e., instruction following) was lower under the high force requirement than under the low force requirement. These results replicate and extend previous findings that instructions interact with social and nonsocial contingencies in controlling human behavior. PMID- 28993243 TI - Diagnosis and staging of caries using spectral factors derived from the blue laser-induced autofluorescence spectrum. AB - OBJECTIVE: The aim of this study was to identify the factors derived from the 405nm laser-induced autofluorescence (AF) spectra that could be used to diagnose and stage caries. MATERIALS AND METHODS: Teeth (20 teeth per stage) were classified as sound, stage II, III, and IV based on a visual and tactile inspection. The specimens were re-examined and reclassified based on micro-CT analysis. From the teeth, the AF was obtained using a 405nm laser. Three spectral factors (spectral slope at 550-600nm, area under the curve at 500-590nm, and two peak ratio between 625 and 667nm) were derived from the AF spectra. Using these factors, the diagnosis and staging of caries were tested, and the results were compared with those of DIAGNOdent. RESULTS: After micro-CT analysis, only 13, 11, and 13 teeth were reclassified as stages II, III, and IV, respectively. The reclassified groups showed less data overlap between the stages, and the spectral slope was 40.1-74.6, 27.5-39.6, 11.1-27.4, and 1.0-9.7 for sound, stage II, III, and IV, respectively. The differentiation of stages III and IV using DIAGNOdent appeared to be difficult due to the considerable data overlap. CONCLUSION: Among the factors tested, the spectral slope at 550-600nm showed the best match with the caries specimens, in which their stage had been identified precisely. CLINICAL SIGNIFICANCE: The 405nm laser-induced AF spectra can be applied to the diagnosis and staging of caries alone or in conjunction with conventional methods, such as visual, tactile, and X-ray inspection. PMID- 28993246 TI - Vitamin D and the paraventricular nucleus: Relevance for type 2 diabetes. AB - Vitamin D deficiency is linked to type 2 diabetes and we recently showed this may be through action of vitamin D in the paraventricular nuclei (PVN) in the hypothalamus of the brain. This review focuses on the known roles of the PVN in glucose control and how previously discovered actions of vitamin D in other tissues may translate to action in the PVN. Specifically, we focus on the role of insulin and inflammation in the hypothalamus and how these may be modified through vitamin D action. PMID- 28993247 TI - The evolution of the Glycomic Codes of extracellular matrices. AB - The extracellular matrices (ECMs) of living organisms are compartments responsible for maintenance of cell shape, cell adhesion, and cell communication. They are also involved in cell signaling and defense against the attack of pathogens. The plant cell walls have been recently defined as encoded structures that combine polysaccharides with other encoded structures (proteins and phenolic compounds). The term Glycomic Code has been used to define the set of mechanisms that generate cell wall architecture (the combination of polymers of different types) and biological function. Here, the composition of the extracellular matrices of archaea, bacteria, animals, fungi, algae, and plants was compared to understand how the Glycomic Code of these different organisms operate to produce polysaccharides and therefore how the Glycomic Code may have evolved in nature. It was found that the heterotrophs display EMC polysaccharides containing aminosugars (nitrogen-based polysaccharides) whereas the photosynthetic organisms have cellulose-based walls, with polymers that hardly present aminosugars in its composition. Another subgroup is of the organisms containing EMCs with sulfated polysaccharides (animals and red algae). The main hemicellulose found in plants (xyloglucan) is used as a case study along with other seed cell wall storage polysaccharides of plants to exemplify the evolution of the Glycomic Code in plants. Overall, the trends observed in this work shows for the first time how the Glycomic Code in ECMs of living organisms may have evolved and diversified in nature. PMID- 28993248 TI - What is code biology? AB - Various independent discoveries have shown that many organic codes exist in living systems, and this implies that they came into being during the history of life and contributed to that history. The genetic code appeared in a population of primitive systems that has been referred to as the common ancestor, and it has been proposed that three distinct signal processing codes gave origin to the three primary kingdoms of Archaea, Bacteria and Eukarya. After the genetic code and the signal processing codes, on the other hand, only the ancestors of the eukaryotes continued to explore the coding space and gave origin to splicing codes, histone code, tubulin code, compartment codes and many others. A first theoretical consequence of this historical fact is the idea that the Eukarya became increasingly more complex because they maintained the potential to bring new organic codes into existence. A second theoretical consequence comes from the fact that the evolution of the individual rules of a code can take an extremely long time, but the origin of a new organic code corresponds to the appearance of a complete set of rules and from a geological point of view this amounts to a sudden event. The great discontinuities of the history of life, in other words, can be explained as the result of the appearance of new codes. A third theoretical consequence comes from the fact that the organic codes have been highly conserved in evolution, which shows that they are the great invariants of life, the sole entities that have gone intact through billions of years while everything else has changed. This tells us that the organic codes are fundamental components of life and their study - the new research field of Code Biology - is destined to become an increasingly relevant part of the life sciences. PMID- 28993249 TI - Spider acetylcholine binding proteins: An alternative model to study the interaction between insect nAChRs and neonicotinoids. AB - Acetylcholine binding proteins (AChBPs) are homologs of extracellular domains of nicotinic acetylcholine receptors (nAChRs) and serve as models for studies on nAChRs. Particularly, studies on invertebrate nAChRs that are limited due to difficulties in their heterologous expression have benefitted from the discovery of AChBPs. Thus far, AChBPs have been characterized only in aquatic mollusks, which have shown low sensitivity to neonicotinoids, the insecticides targeting insect nAChRs. However, AChBPs were also found in spiders based on the sequence and tissue expression analysis. Here, we report five AChBP subunits in Pardosa pseudoannulata, a predator enemy against rice insect pests. Spider AChBP subunits shared higher sequence similarities with nAChR subunits of both insects and mammals compared with mollusk AChBP subunits. The AChBP1 subunit of P. pseudoannulata (Pp-AChBP) was then expressed in Sf9 cells. The Ls-AChBP from Lymnaea stagnalis was also expressed for comparison. In both AChBPs, one ligand site per subunit was present at each interface between two adjacent subunits. Neonicotinoids had higher affinities (7.9-18.4 times based on Kd or Ki values) for Pp-AChBP than for Ls-AChBP, although epibatidine and alpha-bungarotoxin showed higher affinities for Ls-AChBP. These results indicate that spider AChBP could be used as an alternative model to study the interaction between insect nAChRs and neonicotinoids. PMID- 28993250 TI - Monoaminergic descending pathways contribute to modulation of neuropathic pain by increasing-intensity treadmill exercise after peripheral nerve injury. AB - This study characterizes the impact of increasing-intensity treadmill exercise (iTR) on noradrenergic (NE) and serotonergic (5HT) modulation of neuropathic pain. Following sciatic nerve transection and repair (SNTR) rats developed significant mechanical and thermal hyperalgesia that was partially prevented by iTR performed during the first 2weeks after injury. Marked decrease in the expression of 5HT2A and alpha1A and beta-, but not alpha2A adrenergic receptors in the spinal cord dorsal horn was associated to SNTR and recovered by iTR, particularly in lamina II. iTR significantly increased 5HT2A in periaqueductal grey (PAG), raphe magnus (RM) and dorsal raphe nucleus (DRN), with a pattern suggesting reorganization of serotonergic excitatory interconnections between PAG and DRN. iTR also increased the expression of alpha1A in locus coeruleus (LC) and DRN, and beta2 in LC, indicating that exercise enhanced activity of NE neurons, likely by activating autologous projections from DRN and PAG. iTR hypoalgesia was antagonized by blockade of beta2 and 5HT2A receptors with administration of butoxamine and ketanserin. The neurotoxin DSP4 was injected to induce depletion of NE projections from LC before starting iTR. DSP4 treatment worsened mechanical hyperalgesia, but iTR hypoalgesia was similarly produced. Moreover, 5HT2A expression in LC further increased after DSP4 injection, all these results suggesting an intrinsic regulation of 5HT and NE activity between PAG, DRN and LC neurons activated by iTR. Finally, iTR significantly reduced microglial reactivity in LC and increased non-microglial BDNF expression, an effect that was reverted by butoxamine, implicating BDNF regulation in central 5HT/NE actions on neuropathic pain. PMID- 28993253 TI - Regulation and functional diversification of root hairs. AB - Root hairs result from the polar outgrowth of root epidermis cells in vascular plants. Root hair development processes are regulated by intrinsic genetic programs, which are flexibly modulated by environmental conditions, such as nutrient availability. Basic programs for root hair development were present in early land plants. Subsequently, some plants developed the ability to utilize root hairs for specific functions, in particular, for interactions with other organisms, such as legume-rhizobia and host plants-parasites interactions. In this review, we summarize the molecular regulation of root hair development and the modulation of root hairs under limited nutrient supply and during interactions with other organisms. PMID- 28993252 TI - H/D exchange mass spectrometry and statistical coupling analysis reveal a role for allostery in a ferredoxin-dependent bifurcating transhydrogenase catalytic cycle. AB - Recent investigations into ferredoxin-dependent transhydrogenases, a class of enzymes responsible for electron transport, have highlighted the biological importance of flavin-based electron bifurcation (FBEB). FBEB generates biomolecules with very low reduction potential by coupling the oxidation of an electron donor with intermediate potential to the reduction of high and low potential molecules. Bifurcating systems can generate biomolecules with very low reduction potentials, such as reduced ferredoxin (Fd), from species such as NADPH. Metabolic systems that use bifurcation are more efficient and confer a competitive advantage for the organisms that harbor them. Structural models are now available for two NADH-dependent ferredoxin-NADP+ oxidoreductase (Nfn) complexes. These models, together with spectroscopic studies, have provided considerable insight into the catalytic process of FBEB. However, much about the mechanism and regulation of these multi-subunit proteins remains unclear. Using hydrogen/deuterium exchange mass spectrometry (HDX-MS) and statistical coupling analysis (SCA), we identified specific pathways of communication within the model FBEB system, Nfn from Pyrococus furiosus, under conditions at each step of the catalytic cycle. HDX-MS revealed evidence for allosteric coupling across protein subunits upon nucleotide and ferredoxin binding. SCA uncovered a network of co evolving residues that can provide connectivity across the complex. Together, the HDX-MS and SCA data show that protein allostery occurs across the ensemble of iron-sulfur cofactors and ligand binding sites using specific pathways that connect domains allowing them to function as dynamically coordinated units. PMID- 28993254 TI - Editorial Comment. PMID- 28993251 TI - Hypoxia-ischemia modifies postsynaptic GluN2B-containing NMDA receptor complexes in the neonatal mouse brain. AB - The N-methyl-d-aspartate-type glutamate receptor (NMDAR)-associated multiprotein complexes are indispensable for synaptic plasticity and cognitive functions. While purification and proteomic analyses of these signaling complexes have been performed in adult rodent and human brain, much less is known about the protein composition of NMDAR complexes in the developing brain and their modifications by neonatal hypoxic-ischemic (HI) brain injury. In this study, the postsynaptic density proteins were prepared from postnatal day 9 naive, sham-operated and HI injured mouse cortex. The GluN2B-containing NMDAR complexes were purified by immunoprecipitation with a mouse GluN2B antibody and subjected to mass spectrometry analysis for determination of the GluN2B binding partners. A total of 71 proteins of different functional categories were identified from the naive animals as native GluN2B-interacting partners in the developing mouse brain. Neonatal HI reshaped the postsynaptic GluN2B interactome by recruiting new proteins, including multiple kinases, into the complexes; and modifying the existing associations within 1h of reperfusion. The early responses of postsynaptic NMDAR complexes and their related signaling networks may contribute to molecular processes leading to cell survival or death, brain damage and/or neurological disorders in term infants with neonatal encephalopathy. PMID- 28993255 TI - Relations of mitochondrial genetic variants to measures of vascular function. AB - Mitochondrial genetic variation with resultant alterations in oxidative phosphorylation may influence vascular function and contribute to cardiovascular disease susceptibility. We assessed relations of peptide-encoding variants in the mitochondrial genome with measures of vascular function in Framingham Heart Study participants. Of 258 variants assessed, 40 were predicted to have functional consequences by bioinformatics programs. A maternal pattern of heritability was estimated to contribute to the variability of aortic stiffness. A putative association with a microvascular function measure was identified that requires replication. The methods we have developed can be applied to assess the relations of mitochondrial genetic variation to other phenotypes. PMID- 28993256 TI - Biochemical characterization and low-resolution SAXS structure of an exo polygalacturonase from Bacillus licheniformis. AB - Among the structural polymers present in the plant cell wall, pectin is the main component of the middle lamella. This heterogeneous polysaccharide has an alpha 1,4 galacturonic acid backbone, which can be broken by the enzymatic action of pectinases, such as exo-polygalacturonases, that sequentially cleave pectin from the non-reducing ends, releasing mono or di-galacturonic acid residues. Constant demand for pectinases that better suit industrial requirements has motivated identification and characterization of novel enzymes from diverse sources. Bacillus licheniformis has been used as an important source for bioprospection of several industrial biomolecules, such as surfactants and enzymes, including pectate lyases. Here we cloned, expressed, purified, and biochemically and structurally characterized an exo-polygalacturonase from B. licheniformis (BlExoPG). Its low-resolution molecular envelope was derived from experimental small-angle scattering data (SAXS). Our experimental data revealed that BlExoPG is a monomeric enzyme with optimum pH at 6.5 and optimal temperature of approximately 60 degrees C, at which it has considerable stability over the broad pH range from 5 to 10. After incubation of the enzyme for 30min at pH ranging from 5 to 10, no significant loss of the original enzyme activity was observed. Furthermore, the enzyme maintained residual activity of greater than 80% at 50 degrees C after 15h of incubation. BlExoPG is more active against polygalacturonic acid as compared to methylated pectin, liberating mono galacturonic acid as a unique product. Its enzymatic parameters are Vmax=4.18MUM.s-1,Km=3.25mgmL-1 and kcat=2.58s-1. PMID- 28993257 TI - Fecobionics: Integrating Anorectal Function Measurements. PMID- 28993258 TI - Twenty-Year Comparative Analysis of Patients With Autoimmune Liver Diseases on Transplant Waitlists. AB - BACKGROUND & AIMS: The rarity of autoimmune liver disease poses challenges to epidemiology studies. However, waitlists for liver transplantation can be used to study patients with end-stage liver diseases. We used these waitlists to assess trends in numbers and demographics of patients awaiting liver transplant for primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), or autoimmune hepatitis (AIH). METHODS: We collected data from UK and US national registries for all adults on liver transplant waitlists, from January 1, 1995, through December 31, 2014. We analyzed data from patients with PBC (n = 1434 in the United Kingdom and n = 5598 in the United States), PSC (n = 1093 in the United Kingdom and n = 6820 in the United States), and AIH (n = 538 in the United Kingdom and n = 4949 in the United States). Numbers of listings per year were adjusted to the estimated populations during each year. Regression analyses were used to examine trends and comparative statistics were used to evaluate differences in individual characteristics among groups. RESULTS: Over the total study period, listings for PBC were 1.2 and 1.0 per million population per year in the United Kingdom and United States, respectively; for PSC, 0.9 and 1.2 per million population per year; and for AIH, 0.5 and 0.8 per million population per year. Over the period studied, numbers of listings for PBC decreased by 50% in both countries; changes in numbers of listings for PSC and AIH were smaller and not consistent between countries. By 2014, PSC had become the leading indication for liver transplantation among patients with autoimmune liver diseases in both countries. Median patient ages at time of listing were lower than those reported as median age of diagnosis for AIH and PBC. The ratio of women:men with PBC decreased by almost 50% from 1995 through 2014. Men with PSC were placed on the waitlist with higher disease severity scores than women in both countries. Among patients with PBC, those of black race were under-represented on waitlists from both countries. Among patients with PSC, Hispanics were under-represented on waitlists in the United States. Patients of non-white races were placed on waitlists at younger ages for all diseases; age differences in waitlist placement varied by up to 10 years, depending on race, among patients with PBC. CONCLUSIONS: In an analysis of data collected from UK and US national liver transplant registries over 20 years, we found that PSC has become the leading indication for liver transplantation among patients with autoimmune liver diseases. Numbers of patients with PBC placed on waitlists, and the ratio of women:men with PBC, each decreased by almost 50%, possibly due to increased treatment with ursodeoxycholic acid. Within groups of patients on the transplant waitlist for PBC, PSC, or AIH, we found differences in age, sex, disease severity scores, and ethnicity between diseases and countries that require further study. PMID- 28993259 TI - Regional Patterns of Olmesartan Prescription and the Prevalence of Duodenal Villous Atrophy Throughout the United States. PMID- 28993260 TI - Improved Bone Microarchitecture in Patients With Celiac Disease After 3 Years on a Gluten-Free Diet. PMID- 28993261 TI - Volatile Organic Compounds in Feces Associate With Response to Dietary Intervention in Patients With Irritable Bowel Syndrome. AB - BACKGROUND & AIMS: Dietary interventions are effective in management of patients with irritable bowel syndrome (IBS), although responses vary. We investigated whether fecal levels of volatile organic compounds (VOCs) associate with response to dietary interventions in patients with IBS. METHODS: Adults who fulfilled the Rome III criteria for IBS were recruited to a 2x2 factorial randomized controlled trial. Patients were randomly assigned to a group counselled to follow a diet low in fructans, galacto-oligosaccharides, lactose, fructose, and polyols (low-FODMAP diet, n = 46) or a group that received placebo dietary advice (sham diet, n = 47) for 4 weeks. Patients from each group were also given either a multi-strain probiotic or placebo supplement. Response was defined as a reduction of 50 points or more on the validated IBS symptom scoring system. Fecal samples were collected from participants at baseline and end of the 4-week study period; VOCs were analyzed by a gas-chromatography sensor device. VOC profiles were determined using a pipeline involving wavelet transformation followed by feature selection based on random forest. A partial least squares classifier was constructed to classify VOC profiles by response and accuracies were determined using 10-fold cross-validation. RESULTS: Data from 93 patients who completed the study (63 female) were used in the final analysis. More patients responded to the low FODMAP diet (37/46, 80%) than the sham diet (21/47, 45%) (P < .001), but there was no difference in response between patients given the probiotic (31/49, 63%) vs the placebo (27/44, 61%) (P = .850), with no interaction between the diet and supplement interventions. At baseline, VOC profiles contained 15 features that classified response to the low-FODMAP diet with a mean accuracy of 97% (95% CI, 96%-99%) and 10 features that classified response to probiotic with a mean accuracy of 89% (95% CI, 86%-92%). End of treatment models achieved similar predictive powers and accuracies. CONCLUSION: Fecal VOC profiling is a low cost, non-invasive tool that might be used to predict responses of patients with IBS to low-FODMAP diet and probiotics and identify their mechanisms of action. ISRCTN registry no: 02275221. PMID- 28993262 TI - Outcomes 7 Years After Infliximab Withdrawal for Patients With Crohn's Disease in Sustained Remission. AB - BACKGROUND & AIMS: Little is known about long-term outcomes of patients with Crohn's disease (CD) after infliximab withdrawal. We aimed to describe the long term outcomes of patients with CD in clinical remission after infliximab treatment was withdrawn. METHODS: We performed a retrospective analysis of data from the 115 patients included in the infliximab discontinuation in patients with CD in stable remission on combined therapy with antimetabolites (STORI) study, performed at 20 centers in France and Belgium from March 2006 through December 2009. The STORI cohort was a prospective analysis of risk and factors associated with relapse following withdrawal of maintenance therapy with infliximab, maintained on antimetabolites, while in clinical remission. We collected data from the end of the study until the last available follow-up examination on patient surgeries, new complex perianal lesions (indicating major complications), and need for and outcomes of restarting therapy with infliximab or another biologic agent. The de-escalation strategy was considered to have failed when a major complication or infliximab restart failure occurred. RESULTS: Of the 115 patients initially included, data from 102 patients (from 19 of the 20 study centers) were included in the final analysis. The median follow-up time was 7 years. Twenty-one percent of the patients did not restart treatment with infliximab or another biologic agent and did not have a major complication 7 years after infliximab withdrawal (95% CI, 13.1-30.3). Among patients who restarted infliximab, treatment failed for 30.1% 6 years after restarting (95% CI, 18.5-42.5). Overall, at 7 years after stopping infliximab therapy, major complications occurred in 18.5% of patients (95% CI, 10.2-26.8) whereas 70.2% of patients had no failure of the de-escalation strategy (95% CI, 60.2-80.1). Factors independently associated with major complications were upper gastrointestinal location of disease, white blood cell count >= 5.0 * 109/L, and hemoglobin level <=12.5 g/dL at the time of infliximab withdrawal. Patients with at least 2 of these factors had a more than 40% risk of major complication in the 7 years following infliximab withdrawal. CONCLUSIONS: In a long-term follow-up of the STORI cohort (7 years) one fifth of the patients did not restart infliximab or another biologic agent and did not develop major complications. Seventy percent of patients had no failure of the de-escalation strategy (no major complication and no failure of infliximab restart). PMID- 28993263 TI - Angiotensin 1-7 in the rostro-ventrolateral medulla increases blood pressure and splanchnic sympathetic nerve activity in anesthetized rats. AB - Angiotensin 1-7 (ANG-(1-7)), a derivative of angiotensin I or II, is involved in the propagation of sympathetic output to the heart and vasculature, and the receptor for ANG-(1-7), the Mas receptor, is expressed on astrocytes in the rostral ventrolateral medulla (RVLM). We recorded blood pressure (BP) and splanchnic sympathetic nerve activity (SSNA) before and after focal injection of ANG-(1-7) into the RVLM of rats. Unilateral injection of ANG-(1-7) into the RVLM, acting through the Mas receptor, increased SSNA and BP, and glutamate receptor antagonists, CNQX and D-AP5, partially reduced the ANG-(1-7) effect. ATP is often co-released with glutamate, and blocking ATP with PPADS also reduced the pressor response to microinjection of ANG-(1-7) within the RVLM. The effects of ANG-(1-7) were blocked by the MAS receptor antagonist, A-779 (which had no consistent effect on blood pressure or sympathetic nerve activity when injected on its own). We conclude that astrocytes in the RVLM participate in central, angiotensin dependent regulation of blood pressure and sympathetic nerve activity, and the Mas receptor, when activated by ANG-(1-7), elicits the release of the gliotransmitters, glutamate and ATP. These gliotransmitters then cause an increase in sympathetic nerve activity and blood pressure by interacting with AMPA/kainate and P2X receptors in the RVLM. PMID- 28993264 TI - Sensory-mechanical effects of a dual bronchodilator and its anticholinergic component in COPD. AB - This randomized, double-blind, crossover study examined the physiological rationale for using a dual long-acting bronchodilator (umeclidinium/vilanterol (UME/VIL)) versus its muscarinic-antagonist component (UME) as treatment for dyspnea and exercise intolerance in moderate COPD. After each 4-week treatment period, subjects performed pulmonary function and symptom-limited constant-work rate cycling tests with diaphragm electromyogram (EMGdi), esophageal (Pes), gastric (Pga) and transdiaphragmatic (Pdi) pressure measurements. Fourteen subjects completed the study. Both treatments improved spirometry and airway resistance. UME/VIL had larger increases in FEV1 (+0.14+/-0.23L, p<0.05) but no added reduction in lung hyperinflation compared with UME. Isotime during exercise after UME/VIL versus UME (p<0.05): "unpleasantness of breathing" fell 0.8+/-1.3 Borg units; mean expiratory flow and ventilation increased; Pdi and Pga decreased. There were no treatment differences in endurance time, breathing pattern, operating lung volumes, inspiratory neural drive (EMGdi) or respiratory muscle effort (Pes swings) during exercise. UME/VIL compared with UME was associated with reduced breathing unpleasantness reflecting improved airway and respiratory muscle function during exercise. PMID- 28993265 TI - The Concept of Contexts in Pain: Generalization of Contextual Pain-Related Fear Within a de Novo Category of Unique Contexts. AB - : The experience of unpredictable pain fluctuations can trigger anticipatory pain related fear. When discrete predictors for pain are lacking, fear typically accrues to the broader environmental context: a phenomenon referred to as contextual pain-related fear. We examined whether conceptual similarity between discrete contexts facilitates pain-related fear generalization; this mechanism is known as category-level fear generalization. Using a voluntary joystick movement paradigm, pain-free participants performed movements in 2 contexts (within subjects design); context was manipulated by varying background color screens. In the predictable context, one movement predicted pain and another did not. In the unpredictable context, 2 other movements never predicted pain but pain was unpredictably delivered during the context. Participants subsequently learned to categorize novel background colors (ie, generalization contexts) as being similar to either the unpredictable or predictable pain context. Then we tested fear generalization to these novel contexts. We measured self-reported pain-related fear, expectancy, and eyeblink startle. Results indicated higher pain-related fear reports, but no elevated startle responses, for generalization contexts that were trained to be similar to the original unpredictable context rather than the predictable pain context. This highlights a potential pathway through which neutral contexts can elicit pain-related fear and motivate avoidance behavior associated with chronic pain disability. PERSPECTIVE: Self-reported pain-related fear and expectancy of painful outcome in response to a context associated with unpredictable pain generalizes to perceptually distinct contexts that are trained to be conceptually similar to the unpredictable pain context. Category-level generalization may be a pathway contributing to spreading of fear and avoidance in chronic pain. PMID- 28993266 TI - A "protective umbrella" nanoplatform for loading ICG and multi-modal imaging guided phototherapy. AB - In order to prevent the aggregation of ICG and enhance its stability, a novel nanoplatform (TiO2:Yb,Ho,F-beta-CD@ICG/HA) was designed for NIR-induced phototherapy along with multi-mode imaging(UCL/MRI/Flu). In this nanosysytem: TiO2:Yb,Ho,F was used as upconversion materials and applied in vivo for the first time; beta-CD acted as a "protective umbrella" to load separated ICG and avoid the low phototherapy efficiency because of its aggregation; HA was the capping agent of beta-CD to prevent ICG unexpected leaking and a target to recognize CD44 receptor. The nanosystem exhibited excellent size (~200 nm) and photo- and thermal-stability, preferable reactive oxygen yield and temperature response (50.4 degrees C) under 808 nm laser. It could efficiently target and suppress tumor growth. The imaging ability (UCL/MRI) of TiO2:Yb,Ho,F could facilitate diagnosis of the tumor, especially for deep tissues. Altogether, our work successfully improved the phototherapy efficacy through incorporating the ICG into the cavity of beta-CD and applied TiO2:Yb,Ho,F for upconversion imaging in vivo. PMID- 28993267 TI - On selecting a minimal set of in vitro assays to reliably determine estrogen agonist activity. AB - The US EPA is charged with screening chemicals for their ability to be endocrine disruptors through interaction with the estrogen, androgen and thyroid axes. The agency is exploring the use of high-throughput in vitro assays to use in the Endocrine Disruptor Screening Program (EDSP), potentially as replacements for lower-throughput in vitro and in vivo tests. The first replacement is an integrated computational and experimental model for estrogen receptor (ER) activity, to be used as an alternative to the EDSP Tier 1 in vitro ER binding and transactivation assays and the in vivo uterotrophic bioassay. The ER agonist model uses a set of 16 in vitro assays that incorporate multiple technologies and cell lines and probe multiple points in the ER pathway. Here, we demonstrate that subsets of assays with as few as 4 assays can predict the activity of all 1811 chemicals tested with accuracy equivalent to that of the full 16-assay model. The prediction accuracy against reference chemicals is higher than that of the full chemical set, partly because the larger set contains many chemicals that can cause a variety of types of assay interference There are multiple accurate assay subsets, allowing flexibility in the construction of a multiplexed assay battery. We also discuss the issue of challenging chemicals, i.e. those that can give false positive results in certain assays, and could hence be more problematic when only a few assays are used. PMID- 28993268 TI - Nanotoxicological and teratogenic effects: A linkage between dendrimer surface charge and zebrafish developmental stages. AB - This article reports novel results about nanotoxicological and teratogenic effects of the PAMAM dendrimers DG4 and DG4.5 in zebrafish (Danio rerio). Zebrafish embryos and larvae were used as a rapid, high-throughput, cost effective whole-animal model. The objective was to provide a more comprehensive and predictive developmental toxicity screening of DG4 and DG4.5 and test the influence of their surface charge. Nanotoxicological and teratogenic effects were assessed at developmental, morphological, cardiac, neurological and hepatic level. The effect of surface charge was determined in both larvae and embryos. DG4 with positive surface charge was more toxic than DG4.5 with negative surface charge. DG4 and DG4.5 induced teratogenic effects in larvae, whereas DG4 also induced lethal effects in both zebrafish embryos and larvae. However, larvae were less sensitive than embryos to the lethal effects of DG4. The platform of assays proposed and data obtained may contribute to the characterization of hazards and differential effects of these nanoparticles. PMID- 28993269 TI - Hydrogen peroxide resistance in Strigomonas culicis: Effects on mitochondrial functionality and Aedes aegypti interaction. AB - Reactive oxygen species (ROS) are toxic molecules involved in several biological processes such as cellular signaling, proliferation, differentiation and cell death. Adaptations to oxidative environments are crucial for the success of the colonization of insects by protozoa. Strigomonas culicis is a monoxenic trypanosomatid found in the midgut of mosquitoes and presenting a life cycle restricted to the epimastigote form. Among S. culicis peculiarities, there is an endosymbiotic bacterium in the cytoplasm, which completes essential biosynthetic routes of the host cell and may represent an intermediary evolutive step in organelle origin, thus constituting an interesting model for evolutive researches. In this work, we induced ROS resistance in wild type S. culicis epimastigotes by the incubation with increasing concentrations of hydrogen peroxide (H2O2), and compared the oxidative and energetic metabolisms among wild type, wild type-H2O2 resistant and aposymbiotic strains. Resistant protozoa were less sensitive to the oxidative challenge and more dependent on oxidative phosphorylation, which was demonstrated by higher oxygen consumption and mitochondrial membrane potential, increased activity of complexes II-III and IV, increased complex II gene expression and higher ATP production. Furthermore, the wild type-H2O2 resistant strain produced reduced ROS levels and showed lower lipid peroxidation, as well as an increase in gene expression of antioxidant enzymes and thiol-dependent peroxidase activity. On the other hand, the aposymbiotic strain showed impaired mitochondrial function, higher H2O2 production and deficient antioxidant response. The induction of H2O2 resistance also led to a remarkable increase in Aedes aegypti midgut binding in vitro and colonization in vivo, indicating that both the pro-oxidant environment in the mosquito gut and the oxidative stress susceptibility regulate S. culicis population in invertebrates. PMID- 28993270 TI - Reduced silent information regulator 1 signaling exacerbates sepsis-induced myocardial injury and mitigates the protective effect of a liver X receptor agonist. AB - Myocardial injury and dysfunction are critical manifestations of sepsis. Previous studies have reported that liver X receptor (LXR) activation is protective during sepsis. However, whether LXR activation protects against septic heart injury and its underlying mechanisms remain elusive. This study was designed to determine the role of LXR activation in the septic heart with a focus on SIRT1 (silent information regulator 1) signaling. Male cardiac-specific SIRT1 knockout mice (SIRT1-/-) and their wild-type littermates were subjected to sepsis by cecal ligation and puncture (CLP) in the presence or absence of LXR agonist T0901317. The survival rate of mice was recorded during the 7-day period post CLP. Our results demonstrated that SIRT1-/- mice suffered from exacerbated mortality and myocardial injury in comparison with their wild-type littermates. Meanwhile, T0901317 treatment improved mice survival, accompanied by significant ameliorations of myocardial injury and dysfunction in wild-type mice but not in SIRT1-/- mice. Furthermore, the levels of myocardial inflammatory cytokines (TNF alpha, IL-6, IL-1beta, MCP-1, MPO and HMGB1), oxidative stress (ROS generation, MDA), endoplasmic-reticulum (ER) stress (protein levels of CHOP, GRP78, GRP94, IRE1alpha, and ATF6), and cardiac apoptosis following CLP were inhibited by T0901317 treatment in wild-type mice but not in SIRT1-/- mice. Mechanistically, T0901317 enhanced SIRT1 signaling and the subsequent deacetylation and activation of antioxidative FoxO1 and anti-ER stress HSF1, as well as the deacetylation and inhibition of pro-inflammatory NF-KappaB and pro-apoptotic P53, thereby alleviating sepsis-induced myocardial injury and dysfunction. Our data support the promise of LXR activation as an effective strategy for relieving heart septic injury. PMID- 28993272 TI - GABAergic over-inhibition, a promising hypothesis for cognitive deficits in Down syndrome. AB - Down syndrome (DS), also known as trisomy 21, is the most common genetic cause of intellectual disability. It is also a model human disease for exploring consequences of gene dosage imbalance on complex phenotypes. Learning and memory impairments linked to intellectual disabilities in DS could result from synaptic plasticity deficits and excitatory-inhibitory alterations leading to changes in neuronal circuitry in the brain of affected individuals. Increasing number of studies in mouse and cellular models converge towards the assumption that excitatory-inhibitory imbalance occurs in DS, likely early during development. Thus increased inhibition appears to be a common trend that could explain synaptic and circuit disorganization. Interestingly using several potent pharmacological tools, preclinical studies strongly demonstrated that cognitive deficits could be restored in mouse models of DS. Clinical trials have not yet provided robust data for therapeutic application and additional studies are needed. Here we review the literature and our own published work emphasizing the over-inhibition hypothesis in DS and their links with gene dosage imbalance paving the way for future basic and clinical research. PMID- 28993271 TI - Temporal changes in glutathione biosynthesis during the lipopolysaccharide induced inflammatory response of THP-1 macrophages. AB - How macrophages maintain redox homeostasis in the inflammatory process, in which a large amount of oxidants are produced, remains elusive. In this study, we investigated the temporal changes in the intracellular glutathione (GSH), the master antioxidant, and the expression of glutamate cysteine ligase (GCL), the rate-limiting enzyme for GSH biosynthesis, in the inflammatory response of human macrophages (THP1 cells) to lipopolysaccharide. Intracellular GSH concentration was decreased significantly in the early phase (~6h) of LPS exposure, and then gradually went back to the basal level in the late phase (9-24h). The expression level of the catalytic subunit of GCL (GCLC) followed a similar pattern of change as GSH: its mRNA and protein levels were reduced in the early phase and then back to basal level in the late phase. In contrast, the expression of the modifier subunit of GCL (GCLM) was significantly increased in the phase of LPS exposure. Activation Nrf2, the transcription factor involved in the induction of both GCLC and GCLM, occurred at as early as 3h after LPS exposure; whereas the activation of NF-kappaB occurred at as early as 30min. Inhibition of NF-kappaB signaling with SN50 prevented the decrease of GCLC and inhibited Nrf2 activation in response to LPS. These data demonstrate time-dependent changes in the expression of GCL and Nrf2 signaling during the inflammatory response, and that the regulation of GCLC and GCLM might be through different pathways in this process. PMID- 28993274 TI - In situ hybridization detection methods for HPV16 E6/E7 mRNA in identifying transcriptionally active HPV infection of oropharyngeal carcinoma: an updating. AB - The aim of this study is to compare 2 in situ hybridization (ISH) detection methods for human papilloma virus (HPV) 16 E6/E7 mRNA, that is, the RNAscope 2.0 High Definition (HD) and the upgraded RNAscope 2.5 HD version. The RNAscope 2.5 HD has recently replaced the RNAscope 2.0 HD detection kit. Therefore, this investigation starts from the need to analytically validate the new mRNA ISH assay and, possibly, to refine the current algorithm for HPV detection in oropharyngeal squamous cell carcinoma with the final goal of applying it to daily laboratory practice. The study was based on HPV status and on generated data, interpreted by a scoring algorithm. The results highlighted that the compared RNAscope HPV tests had a good level of interchangeability and enabled to identify oropharyngeal squamous cell carcinoma that are truly driven by high-risk HPV infection. This was also supported by the comparison of the RNAscope HPV test with HPV E6/E7 mRNA real-time reverse-transcription polymerase chain reaction in a fraction of cases where material for HPV E6/E7 mRNA real-time reverse transcription polymerase chain reaction was available. Furthermore, the algorithm that associates p16 immunohistochemistry with the identification of HPV mRNA by RNAscope was more effective than the one that associated p16 immunohistochemistry with the identification of HPV DNA by ISH. PMID- 28993273 TI - Acute mental stress induces mitochondrial bioenergetic crisis and hyper-fission along with aberrant mitophagy in the gut mucosa in rodent model of stress-related mucosal disease. AB - Psychological stress, depression and anxiety lead to multiple organ dysfunctions wherein stress-related mucosal disease (SRMD) is common to people experiencing stress and also occur as a side effect in patients admitted to intensive care units; however the underlying molecular aetiology is still obscure. We report that in rat-SRMD model, cold restraint-stress severely damaged gut mitochondrial functions to generate superoxide anion (O2*-), depleted ATP and shifted mitochondrial fission-fusion dynamics towards enhanced fission to induce mucosal injury. Activation of mitophagy to clear damaged and fragmented mitochondria was evident from mitochondrial translocation of Parkin and PINK1 along with enhanced mitochondrial proteome ubiquitination, depletion of mitochondrial DNA copy number and TOM 20. However, excess and sustained accumulation of O2*--generating defective mitochondria overpowered the mitophagic machinery, ultimately triggering Bax-dependent apoptosis and NF-kappaB-intervened pro-inflammatory mucosal injury. We further observed that stress-induced enhanced serum corticosterone stimulated mitochondrial recruitment of glucocorticoid receptor (GR), which contributed to gut mitochondrial dysfunctions as documented from reduced ETC complex 1 activity, mitochondrial O2*- accumulation, depolarization and hyper-fission. GR-antagonism by RU486 or specific scavenging of mitochondrial O2*- by a mitochondrially targeted antioxidant mitoTEMPO ameliorated stress induced mucosal damage. Gut mitopathology and mucosal injury were also averted when the perception of mental stress was blocked by pre-treatment with a sedative or antipsychotic. Altogether, we suggest the role of mitochondrial GR-O2*- fission cohort in brain-mitochondria cross-talk during acute mental stress and advocate the utilization of this pathway as a potential target to prevent mitochondrial unrest and gastropathy bypassing central nervous system. PMID- 28993275 TI - The CD4/CD8 ratio of tumor-infiltrating lymphocytes at the tumor-host interface has prognostic value in triple-negative breast cancer. AB - Compelling evidence has demonstrated the prognostic value of tumor-infiltrating lymphocytes (TILs), especially in triple-negative breast cancer (TNBC). However, only a limited number of studies to investigate the importance of the subsets of T cells in TILs have been carried out, less so the significance of the location of these TILs. In this study, we explored in a cohort of 42 consecutive TNBC cases the prognostic significance of TIL subsets at the tumor-host interface (within 1 high-power field [0.5 mm] of the invasive front) and compared them with TILs within the intratumoral stroma. Given the reported importance of TILs in HER2-overexpressing breast cancer, a subset of such tumors was also included for comparison. The range was wide in both locations; nevertheless, the mean CD4+ and CD8+ T cell count was significantly higher at the tumor-host interface than that found within the intratumoral stroma (both P<.0001). The number of CD4+ or CD8+ T cells at either location was not significantly associated with distant relapse free or overall survival. However, the CD4/CD8 ratio at the tumor-host interface was significantly associated with both relapse-free survival (hazard ratio 0.2, P=.002) and overall survival (hazard ratio 0.13, P=.002), whereas this association was not seen for the CD4/CD8 ratio within the intratumoral stroma. As expected, both tumor size and nodal status were significantly associated with survival outcomes. The findings further support the contention that TILs, as markers of regional immune escape, are of prognostic importance in TNBC progression and that the CD4/CD8 ratio of TILs at the tumor-host interface plays a distinctive role, thus appearing to be of clinical relevance. PMID- 28993276 TI - A distinctive subgroup of oral EBV+ B-cell neoplasm with polymorphous features is potentially identical to EBV+ mucocutaneous ulcer. AB - Epstein-Barr virus-positive mucocutaneous ulcer (EBVMCU) is a newly recognized provisional entity included in mature B-cell neoplasm in the latest 2016 World Health Organization Classification. It has a self-limited growth potential with a high predilection for oral cavities and occurs in age-related or iatrogenic immunodeficiency with indolent clinical courses. However, it shares histological features with EBV-positive diffuse large B-cell lymphoma (DLBCL), and this often leads to diagnostic challenges and controversies in patients with an oral EBV positive B-cell neoplasm. The aim of this study was to better characterize and comprehend the pathophysiology of DLBCL and EBVMCU in the oral cavity. We conducted clinicopathologic and recurrent gene mutation analysis of 49 cases (14 EBV positive, 35 EBV negative), including cases diagnosed as DLBCL or B-cell lymphoproliferative disorders with high-grade morphology in the oral cavity. All EBV-positive cases matched the criteria of EBVMCU, with significantly earlier clinical stages than the EBV-negative group (P=.0006). Besides, histological analysis showed that all EBV-positive cases presented polymorphous features, whereas 91.4% (32/35) of the EBV-negative cases showed diffuse and monotonous proliferation (P<.0001). Furthermore, EBV-positive cases presented favorable clinical outcomes without disease-related death or recurrence. Gene mutation analysis (MYD88, CD79A, CD79B, CARD11, and EZH2) revealed that 33.3% (9/27) of EBV-negative cases harbored at least 1 gene mutation, whereas no gene mutation was observed in the EBV-positive group (0/11). These results suggest that oral EBV-positive B-cell lymphoid proliferation with polymorphous features often fulfill the criteria for EBVMCU, with clinicopathologically and genetically distinctive properties. PMID- 28993278 TI - Glutathione salts of O,O-diorganyl dithiophosphoric acids: Synthesis and study as redox modulating and antiproliferative compounds. AB - Reactions of glutathione (GSH) with O,O-diorganyl dithiophosphoric acids (DTPA) were studied to develop bioactive derivatives of GSH. Effective coupling reaction of GSH with DTPA was proposed to produce the ammonium dithiophosphates (GSH-DTPA) between the NH2 group in gamma-glutamyl residue of GSH and the SH group in DTPA. A series of the GSH-DTPA salts based on O-alkyl or O-monoterpenyl substituted DTPA were synthesized. Enhanced radical scavenging activity of the GSH-DTPA over GSH was established with the use of DPPH assay and improved fluorescent assay which utilizes Co/H2O2 Fenton-like reaction. Similarly to GSH, the dithiophosphates induced both pro- and antioxidant effects in vitro attributed to different cellular availability of the compounds. Whereas extracellularly applied GSH greatly stimulated proliferation of cancer cells (PC-3, vinblastine-resistant MCF-7 cells), the GSH-DTPA exhibited antiproliferative activity, which was pronounced for the O-menthyl and O-isopinocampheolyl substituted compounds 3d and 3e (IC50>=1MUM). Our results show that the GSH-DTPA are promising redox modulating and antiproliferative compounds. The approach proposed can be extended to modification and improvement of bioactivity of various natural and synthetic peptides. PMID- 28993277 TI - Structure, folding and stability of a minimal homologue from Anemonia sulcata of the sea anemone potassium channel blocker ShK. AB - Peptide toxins elaborated by sea anemones target various ion-channel sub-types. Recent transcriptomic studies of sea anemones have identified several novel candidate peptides, some of which have cysteine frameworks identical to those of previously reported sequences. One such peptide is AsK132958, which was identified in a transcriptomic study of Anemonia sulcata and has a cysteine framework similar to that of ShK from Stichodactyla helianthus, but is six amino acid residues shorter. We have determined the solution structure of this novel peptide using NMR spectroscopy. The disulfide connectivities and structural scaffold of AsK132958 are very similar to those of ShK but the structure is more constrained. Toxicity assays were performed using grass shrimp (Palaemonetes sp) and Artemia nauplii, and patch-clamp electrophysiology assays were performed to assess the activity of AsK132958 against a range of voltage-gated potassium (KV) channels. AsK132958 showed no activity against grass shrimp, Artemia nauplii, or any of the KV channels tested, owing partly to the absence of a functional Lys Tyr dyad. Three AsK132958 analogues, each containing a Tyr in the vicinity of Lys19, were therefore generated in an effort to restore binding, but none showed activity against any of KV channels tested. However, AsK132958 and its analogues are less susceptible to proteolysis than that of ShK. Our structure suggests that Lys19, which might be expected to occupy the pore of the channel, is not sufficiently accessible for binding, and therefore that AsK132958 must have a distinct functional role that does not involve KV channels. PMID- 28993279 TI - Anti-scorpion venom activity of Thapsia garganica methanolic extract: Histopathological and biochemical evidences. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Thapsia garganica, is a herbal medicine traditionally used as diuretic, emetic and purgative. It is also used as anti scorpion venom in Morocco; however, its protective effects against scorpion venom remain elusive. AIM OF THE STUDY: The present study was undertaken to evaluate anti-venom activity of T. garganica in vivo through histological and biochemical studies. MATERIALS AND METHODS: Methanolic leaves extract of T. garganica was evaluated for anti-venom activity against buthus. occitanus under in vivo conditions. Histopathological and biochemical changes in envenomed and treated mice were also examined. Phytochemical screening was conducted to estimate the major constituents whereas DPPH, beta -Carotene-linoleic acid and reducing power assays were performed to evaluate the anti-oxidant activity of T. garganica extract. RESULTS: Methanolic leaves extract of T. garganica (2g/kg) increased the survival time (> 18h) of mice injected with lethal doses of B. occitanus venom, with remarkable recovery of histology damage. Furthermore T. garganica induced a significant decreased of biochemical markers of kidney, liver and heart function. Phytochemistry screening revealed the presence of phenolic compounds, flavonoids, tannins and steroids/terpenoids, which might explain the bioactivity of the extract. It was also shown that the extract has an exceptionally high antioxidant activity compared to well-known antioxidants used as standards. CONCLUSION: The present study provides strong evidence that support the use of T. garganica as anti-scorpion venom in traditional medicine in Morocco. However, additional studies are required to isolate and identify the metabolites responsible for the activity. PMID- 28993280 TI - Antidiabetic activities of entagenic acid in type 2 diabetic db/db mice and L6 myotubes via AMPK/GLUT4 pathway. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Entada phaseoloides (L.) Merr., a traditional Chinese folk medicine, has been used in treating diabetes and other inflammatory disorders. Our previous study revealed that the triterpene saponins in E.Phaseoloides possessed an antidiabetic effect in type 2 diabetic rats by activating AMP-activated protein kinase (AMPK). Entagenic acid, the principal aglycon, isolated from the seed kernels of E. phaseoloides, has been proposed to possess a significant role in the antidiabetic effect, however, its actual effect and pertinent mechanisms are still unknown. AIM OF THE STUDY: The aim of the present study was to investigate the antidiabetic effect of entagenic acid in a type 2 diabetic animal model (C57BIKsj db/db mice) and its role in the regulation of glucose uptake in L6 myotubes, and to explore the possible molecular mechanisms. MATERIALS AND METHODS: In vivo, average weekly body weight, daily water, food intake and postprandial blood glucose levels, the intraperitoneal insulin tolerance test, glucose tolerance test, serum lipid profiles and pancreatic histopathological changes in db/db mice treated with entagenic acid orally at different doses (5, 10 and 20mg/kg) were assessed and compared with wild-type littermates or vehicle- and metformin-treated db/db mice. In vitro, effects of entagenic acid on the glucose consumption and the phosphorylation of protein kinase B (AKT) and AMPK in L6 myotubes were evaluated. RESULTS: In vivo, entagenic acid significantly lowered postprandial blood glucose levels but not the body weight, normalized the serum lipid imbalance, improved the impaired glucose tolerance, insulin resistance, as well as the pathological changes in pancreatic islets. In vitro, entagenic acid dose-dependently promoted glucose utilization and enhanced the translocation and expression of glucose transporter 4 (GLUT4), and phosphorylation of AMPK but not AKT. CONCLUSIONS: The present study demonstrated that entagenic acid can markedly maintain the glucose homeostasis, improve insulin resistance and ameliorate dyslipidemia. Its antihyperglycemic effect could be caused by promoting AMPK mediated cellular signaling and GLUT4 translocation in muscles. PMID- 28993281 TI - Two miscarriages, consecutive or non-consecutive, does it change something? AB - OBJECTIVES: To assess the rate of anomalies in the etiological evaluation of patients presenting recurrent early miscarriages (RM) according to miscarriage chronology (number of miscarriages, history of live birth and succession of RM). METHODS: Retrospective single centre study including RM, defined as at least 2 miscarriages at less than 14 weeks of gestation (WG) between the 1st January 2012 and the 31st December 2015. Clinical data and etiological evaluation include blood glucose levels, screening for antiphospholipid syndrome (APS), endocrine assessment, vitamin levels, pelvic imaging, karyotyping of both partners, chronic endometritis and thrombophilia screening. RESULTS: Two hundred and eighty-eight patients were included over this period, 118 (41%) patients had no history of live birth. Two hundred and twenty-three (77%) patients had consecutive RM and 65 (22%) patients had non-consecutive RM. For consecutive RM, 62,8% had thrombophilic disorders versus 69,8% for non-consecutive RM (P>0,05); 44,7% had endocrine disorders or vitamin deficiencies versus 39,7%; 34,6% of patients with consecutive RM had uterine anomalies versus 45,5% respectively. No difference was found depending on the recurrence of RM or the history of live birth (P>0.05) apart from the age of the patient. Fifty-nine (17.4%) patients had uterine anomalies. There are 24 chronic endometritis on 31 biospsies performed. Seventy eight (27%) patients were offered treatment. Ninety-four (90%) patients showed good therapy compliance. Eighty-one (78%) patients became pregnant. CONCLUSION: An etiological evaluation provides, for over half of the cases, an etiology or the identification of risk factors responsible for RM, as well as in some cases offering an adapted, efficient, therapeutic approach. This evaluation should be offered regardless of the obstetric history of the patient. PMID- 28993282 TI - Surgical management for lumbar disc herniation in pregnancy. AB - Lumbar disc herniation is a common surgical spine pathology that may be presented during pregnancy. The state of pregnancy complicates the diagnosis and therapeutical management of this entity. Specific considerations rule the decision for surgical intervention, the optimal timing of it and the type of selected procedure in a pregnant patient, due to the potential risks for the fetus. In the last 30 years, evolution in the field of spine surgery has provided options other than open standard discectomy. The well-established concept of "minimal intervention" has led to the development of microdiscectomy and other innovative, full-endoscopic techniques for lumbar discectomy. The aim of the present study is to review the surgical management of lumbar disc herniation in pregnancy and investigate the potential role of minimally invasive spine surgery in this specific population. PMID- 28993283 TI - Identification of berberrubine metabolites in rats by using ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. AB - Berberrubine, an isoquinoline alkaloid isolated from many medicinal plants, possesses diverse pharmacological activities, including glucose-lowering, lipid lowering, anti-inflammatory, and anti-tumor effects. This study aimed to investigate the metabolic profile of berberrubine in vivo. Therefore, a rapid and reliable method using the ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and metabolynxTM software with mass defect filter (MDF) technique was developed. Plasma, bile, urine and feces samples were collected from rats after oral administration of berberrubine with a dose of 30.0mg/kg and analyzed to characterize the metabolites of berberrubine in vivo for the first time. A total of 57 metabolites were identified, including 54 metabolites in urine, 39 metabolites in plasma, 28 metabolites in bile and 18 metabolites in feces. The results indicated that demethylenation, reduction, hydroxylation, demethylation, glucuronidation, and sulfation were the major metabolic pathways of berberrubine in vivo. PMID- 28993284 TI - Babesia microti infection and hemophagocytic lymphohistiocytosis in an immunocompetent patient. AB - Babesiosis is a rare and potentially severe tick-borne illness endemic to the Northeastern and upper Midwestern regions of the USA. Hemophagocytic lymphohistiocytosis is an uncommon condition resulting from over-activation of the immune system. The first known case of babesiosis and hemophagocytic lymphohistiocytosis in an immunocompetent patient is reported here. PMID- 28993285 TI - Insulin-like peptides and DNA/tRNA methyltransferases are involved in the nutritional regulation of female reproduction in Nilaparvata lugens (Stal). AB - Insulin-like peptides (ILPs) sense and transduce nutritional information and are linked to female reproduction in many insect species. Our previous studies have shown that "Target of rapamycin" (TOR) pathway functions through juvenile hormone (JH) to regulate amino acids-mediated vitellogenesis in the brown planthopper, Nilaparvata lugens, one of the most destructive rice pests in Asia. Recent reports have demonstrated that DNA methyltransferases (Dnmts) are also involved in female reproduction of N. lugens. However, the roles of ILPs and Dnmts in the nutritional regulation of female reproduction have not been fully elucidated. ILPs and Dnmts are highly expressed in the adult females after a supplement of amino acids, indicating nutrition-stimulated expression patterns of these genes. RNA interference-mediated depletion of NlILP2 or NlILP4 dramatically decreased the expression levels of NlDnmt1 and NlDnmt2 (tRNA methyltransferase), and resulted in severely impaired ovary growth as well as the substantial reduction of fecundity. Notably, NlILP2 or NlILP4 knockdown led to reduced mRNA accumulation of S6 kinase (S6K), a downstream target of the nutritional TOR pathway, and decreased vitellogenin content in the fat body. Silencing NlDnmt1 or NlDnmt2 effectively suppressed ovary development and decreased female fecundity. However, NlDnmt1 or NlDnmt2 knockdown did not influence the expression of NlILP2 and NlILP4. We infer that amino acids act on ILPs and Dnmts to regulate vitellogenesis and oocyte maturation in N. lugens. PMID- 28993286 TI - SPIRIT trial: A phase III pragmatic trial of an advance care planning intervention in ESRD. AB - : Advance care planning (ACP) is a central tenet of dialysis care, but the vast majority of dialysis patients report never engaging in ACP discussions with their care providers. Over the last decade, we have developed and iteratively tested SPIRIT (Sharing Patient's Illness Representation to Increase Trust), a theory based, patient- and family-centered advance care planning intervention. SPIRIT is a six-step, two-session, face-to-face intervention to promote cognitive and emotional preparation for end-of-life decision making for patients with ESRD and their surrogates. In these explanatory trials, SPIRIT was delivered by trained research nurses. Findings consistently revealed that patients and surrogates in SPIRIT showed significant improvement in preparedness for end-of-life decision making, and surrogates in SPIRIT reported significantly improved post-bereavement psychological outcomes after the patient's death compared to a no treatment comparison condition. As a critical next step, we are conducting an effectiveness implementation study. This study is a multicenter, clinic-level cluster randomized pragmatic trial to evaluate the effectiveness of SPIRIT delivered by dialysis care providers as part of routine care in free-standing outpatient dialysis clinics, compared to usual care plus delayed SPIRIT implementation. Simultaneously, we will evaluate the implementation of SPIRIT, including sustainability. We will recruit 400 dyads of patients at high risk of death in the next year and their surrogates from 30 dialysis clinics in four states. This trial of SPIRIT will generate novel, meaningful insights about improving ACP in dialysis care. TRIAL REGISTRATION: ClinicalTrials.govNCT03138564, registered 05/01/2017. PMID- 28993287 TI - Effectiveness of certified diabetes educators following pre-approved protocols to redesign diabetes care delivery in primary care: Results of the REMEDIES 4D trial. AB - OBJECTIVE: To evaluate changes in HbA1c, blood pressure, and LDLc levels in participants from practices where certified diabetes educators (CDEs) implemented standardized protocols to intensify treatment compared with those receiving usual care. RESEARCH DESIGN AND METHODS: This clustered, randomized, clinical trial was implemented in community-based primary care practices. Fifteen primary care practices and 240 patients with type 2 diabetes were randomized to the intervention (n=175) or usual care (n=65). Participants had uncontrolled HbA1c, blood pressure, or LDLc. The one-year intervention included CDEs implementing pre approved protocols to intensify treatment. Diabetes self-management education was also provided in both study groups. RESULTS: The population was 50.8% male with a mean age of 61years. The HbA1c in the intervention group decreased from 8.8% to 7.8%, (p=0.001) while the HbA1c in the usual care group increased slightly from 8.2% to 8.3%. There was also a significant difference in HbA1c between the two groups (p=0.004). There was not a significant difference between groups for systolic blood pressure (SBP) or LDLc at the end of the intervention. Those in the intervention group were more likely to have glucose-lowering medications intensified and were more likely to have their HbA1c (35% vs 15%), SBP (80% vs 77%) and HbA1c, SBP, and LDLc at goal (11% vs 1.5%) compared with the usual care group. There was no significant difference in intensification of blood pressure or cholesterol medication. CONCLUSIONS: Findings suggest that CDEs following standardized protocols in primary care is feasible and can effectively intensify treatment and improve glycemic control. PMID- 28993288 TI - The Relationship Between Sacral Slope and Symptomatic Isthmic Spondylolysis in a Cohort of High School Athletes: A Retrospective Analysis. AB - BACKGROUND: Spondylolysis with and without anterolisthesis is the most common cause of structural back pain in children and adolescents, but few predictive factors have been confirmed. An association between abnormal sacropelvic orientation and both spondylolysis and spondylolisthesis has been supported in the literature. Sacral slope and other sacropelvic measurements are easily accessible variables that could aid clinicians in assessing active adolescents with low back pain, particularly when the diagnosis of spondylolysis is suspected. OBJECTIVE: To examine the relationship between sacral slope and symptomatic spondylolysis in a cohort of active adolescents. DESIGN: Case-control retrospective study. SETTING: Academic outpatient physiatry practice. PATIENTS: Seventy-four patients of primarily adolescent age (between 12 and 22 years old) with a chief complaint of low back pain and presence of lateral radiographs of the lumbar spine were enrolled. Cases (n = 37) were defined as subjects with evidence of spondylolysis on both radiograph and magnetic resonance imaging of the lumbar spine. Controls (n = 37) were defined as subjects without spondylolysis. METHODS: Using a single sagittal radiograph, taken with the patient standing, a fellowship-trained interventional spine physiatrist measured the sacral slope of each subject (angle between the superior plate of S1 and a horizontal reference on sagittal imaging of the lumbosacral spine). Ages and genders were collected from medical records. MAIN OUTCOME MEASUREMENTS: The primary outcome was mean sacral slope. Mean sacral slope of cases was compared with mean sacral slope of controls with the Student t-test. RESULTS: Ages ranged from 12 to 22 for both groups, with no significant differences in age between the groups (cases: 16.8 +/- 2.3 years; controls: 17.7 +/- 2.7 years). The patients with spondylolysis (cases) consisted of 29 male and 8 female patients, whereas those without spondylolysis (controls) consisted of 15 male and 21 female patients (gender details for 1 patient were not available). The mean sacral slope among cases was 42.4 degrees , whereas the mean sacral slope among controls was 37.4 degrees . The difference achieved significance (P = .014). CONCLUSIONS: The interdependence of positional parameters, such as sacral slope, with anatomic parameters, such as pelvic incidence, can affect lumbar lordosis and therefore upright positioning and loading of the spine. Sacral slope may be an important variable for clinicians to consider when caring for young athletes with low back pain, particularly when the index of suspicion for spondylolysis is high. LEVEL OF EVIDENCE: IV. PMID- 28993289 TI - Sirt1 and Parp1 as epigenome safeguards and microRNAs as SASP-associated signals, in cellular senescence and aging. AB - Cellular senescence (CS) is underlying mechanism of organism aging and is closely interconnected with age-related diseases (ARDs). Thus, any attempt that influences CS, may be undertaken to reverse or inhibit senescence, whereby could prolong healthy life span. Until now, two main proposes are epigenetic and genetic modifications of cell fate. The first one concerns rejuvenation through effective reprogramming in cells undergoing senescence, or derived from very old or progeroid patients, by which is effective in vitro in induced pluripotent stem cells (iPSCs). The second approach concerns modification of senescence signaling pathways like as IGF-induced agents. However, senescence research has experienced an unprecedented advance over recent years, particularly with the discovery that the rate of senescence is controlled, at least to some extent, by epigenetic pathways and biochemical processes conserved in evolution. In this review we try to concentrate on very specific pathways (DNA damage response, DDR, and epigenetic modifiers) and very specific determinants (senescence-associated secretory phenotype, SASP-miRNAs) of human premature aging. A major challenge is to dissect the interconnectedness between the candidate elements and their relative contributions to aging, with the final goal of identifying new opportunities for design of novel anti-aging treatments or avoidance of age associated manifestations. While knowing that aging is unavoidable and we cannot expect its elimination, but prolonging healthy life span is a goal worth serious consideration. PMID- 28993290 TI - Spinal cord injury associated with cervical spinal canal stenosis: Outcomes and prognostic factors. AB - OBJECTIVES: To specify outcomes and identify prognostic factors of neurologic and functional recovery in patients with an acute traumatic spinal cord injury (SCI) associated with cervical spinal canal stenosis (SCS), without spinal instability. METHODS: A retrospective study was conducted using data from a Regional Department for SCI rehabilitation in France. A description of the population characteristics, clinical data and neurological and functional outcomes of all patients treated for acute SCI due to cervical trauma associated with SCS was performed. A statistical analysis provided insights into the prognostic factors associated with the outcomes. RESULTS: Sixty-three patients (mean age 60.1 years) were hospitalized for traumatic SCI with SCS and without instability between January 2000 and December 2012. Falls were the most frequent cause of trauma (77.8%). At admission, most patients had an American Spinal Injury Association Impairment Scale (AIS) grade of C (43.3%) or D (41.7%) and the most frequent neurological levels of injury were C4 (35.7%) and C5 (28.6%). Clinical syndromes were frequently identified (78.6%), with the most frequent being the Brown Sequard plus syndrome (BSPS) (30.9%), followed by central cord syndrome (CCS, 23.8%). Almost 80% of survivors returned to the community, 60% were able to walk and 75% recovered complete voluntary control of bladder function. Identified prognostic factors of favourable functional outcomes were higher AIS at admission, age under 60 years and presence of BSPS or CCS. CONCLUSION: Traumatic SCI, associated with SCS results mostly in incomplete injuries, can cause various syndromes and is associated with favourable functional outcomes. PMID- 28993292 TI - Inter-individual and intragenomic variations in the ITS region of Clonorchis sinensis (Trematoda: Opisthorchiidae) from Russia and Vietnam. AB - Here we examined the intraspecific genetic variability of Clonorchis sinensis from Russia and Vietnam using nuclear DNA sequences (the 5.8S gene and two internal transcribed spacers of the ribosomal cluster). Despite the low level of variability in the ITS1 region, this marker has revealed some features of C. sinensis across multiple geographic regions. The genetic diversity levels for the Russian and Vietnamese populations were similar (0.1 and 0.09%, respectively) but were significantly lower than the C. sinensis from China (0.31%). About half of the sequences of the Chinese (53%) and Korean (47%) populations and about a tenth of the Vietnamese (12%) and Russian (8%) sequences included a 5bp insertion. No sequences with nucleotide substitutions both upstream and downstream of the 5bp insertion were found within the whole data set. The population of northern China had both sequence variants (with substitutions either upstream or downstream of the insertion), while only one of these variants was presented at the other localities. The Vietnamese population had a higher frequency of intragenomic polymorphism than the Russian population (69% vs. 46% and 23% vs. 3% at the 114bp and 339bp positions, respectively). These data are discussed in connection with parasite origin and adaptation, and also its invasive capacity and drug resistance. PMID- 28993291 TI - PAK4 crystal structures suggest unusual kinase conformational movements. AB - : In order for protein kinases to exchange nucleotide they must open and close their catalytic cleft. These motions are associated with rotations of the N-lobe, predominantly around the 'hinge region'. We conducted an analysis of 28 crystal structures of the serine-threonine kinase, p21-activated kinase 4 (PAK4), including three newly determined structures in complex with staurosporine, FRAX486, and fasudil (HA-1077). We find an unusual motion between the N-lobe and C-lobe of PAK4 that manifests as a partial unwinding of helix alphaC. Principal component analysis of the crystal structures rationalizes these movements into three major states, and analysis of the kinase hydrophobic spines indicates concerted movements that create an accessible back pocket cavity. The conformational changes that we observe for PAK4 differ from previous descriptions of kinase motions, and although we observe these differences in crystal structures there is the possibility that the movements observed may suggest a diversity of kinase conformational changes associated with regulation. AUTHOR SUMMARY: Protein kinases are key signaling proteins, and are important drug targets, therefore understanding their regulation is important for both basic research and clinical points of view. In this study, we observe unusual conformational 'hinging' for protein kinases. Hinging, the opening and closing of the kinase sub-domains to allow nucleotide binding and release, is critical for proper kinase regulation and for targeted drug discovery. We determine new crystal structures of PAK4, an important Rho-effector kinase, and conduct analyses of these and previously determined structures. We find that PAK4 crystal structures can be classified into specific conformational groups, and that these groups are associated with previously unobserved hinging motions and an unusual conformation for the kinase hydrophobic core. Our findings therefore indicate that there may be a diversity of kinase hinging motions, and that these may indicate different mechanisms of regulation. PMID- 28993293 TI - Association between Mycobacterium tuberculosis lineage and site of disease in Florida, 2009-2015. AB - BACKGROUND: Mycobacterium tuberculosis is characterized into four global lineages with strong geographical restriction. To date one study in the United States has investigated M. tuberculosis lineage association with tuberculosis (TB) disease presentation (extra-pulmonary versus pulmonary). We update this analysis using recent (2009-2015) data from the State of Florida to measure lineage association with pulmonary TB, the infectious form of the disease. METHODS: M. tuberculosis lineage was assigned based on the spacer oligonucleotide typing (spoligotyping) patterns. TB disease site was defined as exclusively pulmonary or extra pulmonary. We used ORs to measure the association between M. tuberculosis lineages and pulmonary compared to extra-pulmonary TB. The final multivariable model was adjusted for patient socio-demographics, HIV and diabetes status. RESULTS: We analyzed 3061 cases, 83.4% were infected with a Euro-American lineage, 8.4% Indo-Oceanic and 8.2% East-Asian lineage. The majority of the cases (86.0%) were exclusively pulmonary. Compared to the Indo-Oceanic lineage, infection with a Euro-American (AOR=1.87, 95% CI: 1.21, 2.91) or an East-Asian (AOR=2.11, 95% CI: 1.27, 3.50) lineage favored pulmonary disease compared to extra-pulmonary. In a sub-analysis among pulmonary cases, strain lineage was not associated with sputum smear positive status, indicating that the observed association with pulmonary disease is independent of host contagiousness. CONCLUSION: As an obligate pathogen, M. tuberculosis' fitness is directly correlated to its transmission potential. In this analysis, we show that M. tuberculosis lineage is associated with pulmonary disease presentation. This association may explain the predominance in a region of certain lineages compared to others. PMID- 28993294 TI - Structural elucidation and antiaging activity of polysaccharide from Paris polyphylla leaves. AB - To optimize the use of Paris polyphylla resources, a homogenous polysaccharide (PPLP) was obtained from P. polyphylla leaves. Its average molecule weight was 2.95*104Da, and the analysis of monosaccharide composition shown that PPLP consisted of l-arabinose and d-galactose with a molar ratio of 4.2:5.8. Methylation and nuclear magnetic resonance (NMR) spectroscopy data revealed that the backbone of PPLP was comprised of (1->6)-beta-d-galactan, and the branched chains mainly consisted of arabinosyl residues which was linked to backbone via (1->3)-linkages. In addition, the antiaging effect of PPLP was investigated in a d-galactose induced mouse aging model. Compared with model group, the formations of malondialdehyde (MDA) were significantly prevented, and the levels of antioxidant enzymes and total antioxidant capacity (TAOC) were significantly improved in serum and liver in PPLP dose groups. These results demonstrated that PPLP possessed potent antiaging capacity. PMID- 28993295 TI - Design, synthesis and collagenase inhibitory activity of some novel phenylglycine derivatives as metalloproteinase inhibitors. AB - Metalloproteases are a class of proteases having metal ion(s) at their catalytic sites. Bacterial collagenases are involved in human gas gangrene, periodontal diseases, food etc. The Clostridium collagenase occurs in two isoforms COL_G and Col_H. The present work is based on the protein structure-based approach for the development of collagenase inhibitors. The sequence analysis and structural alignment of both isoforms showed significant similarity in active site except aspartate switch present in Col_H. The homology model was developed and validated for Col_H peptidase domain with open aspartate switch followed by the docking of designed ligands. Compound 8b showed better interaction due to the presence of the nitro group. The N-benzyl-arylsulfonyl-phenylglycine derivatives were synthesized and characterized by FT-IR, 1H NMR, 13C NMR and mass spectral analysis. The compounds were evaluated for C. histolyticum collagenase inhibitory activity using gelatin-ninhydrin based assay. Compounds 5b, 3b, 11b, 6b and 8b with IC50 of 24.34MUM, 29.61MUM, 28.39MUM, 31.4 and 32.11MUM respectively were found to be more active. Further, The Ki of most active compound 5b was found to be 22.02MUM showing the competitive mode of inhibition of the enzyme. The activity of the derivatives showed correlation with the docking results. PMID- 28993296 TI - Poly(N,N-dimethylamino)ethyl methacrylate/sodium alginate multilayers and their interaction with proteins/enzymes. AB - The aim of the present work is to construct and investigate the properties of novel polyelectrolyte multilayers consisting of poly(N,N-dimethylamino)ethyl methacrylate (PDMAEMA) and sodium alginate (SA). The influence of PDMAEMA's pH dependent ionization degree on the charge balance, thickness and roughness of the multilayer films was assessed by potentiometric titrations, dye sorption and atomic force microscopy. Moreover, the cross-linking of PDMAEMA/SA films with a dihalogenated aromatic derivative with high reactivity (alpha,alpha'-dichloro-p xylene) by means of Menshutkin reaction and the stability of the multilayer architecture to repeated treatments with NaOH are demonstrated. Also, the interaction of the obtained films with various proteins/enzymes (pepsin, bovine serum albumin, haemoglobin and lysozyme) is investigated. It was found that biomolecules with the isoelectric point in the acidic region of pH were adsorbed in a higher amount than the biomolecules with the isoelectric point in the basic region of pH. PMID- 28993297 TI - Facile synthesis of high performance porous magnetic chitosan - polyethylenimine polymer composite for Congo red removal. AB - A new porous magnetic chitosan-polyethylenimine (Fe3O4/CS-PEI) polymer composite was synthesized by crosslinking chitosan (CS) with polyethylenimine (PEI) in the present of FeCl3.6H2O and FeCl2.4H2O in alkaline condition and applied to remove congo red (CoR) from aqueous solutions. The Fe3O4/CS-PEI composite was characterized by SEM, XRD, TGA and FT-IR analysis. The polymer composite owned high positive charge, large surface area, multi-level pore distribution and magnetic responsiveness. The porous magnetic Fe3O4/CS-PEI composite showed ultrahigh capacity (1876mg/g) for CoR removal. It removed over 99.3% of CoR (100mg/L) when the dosage was over 1.4g/L. A higher temperature was benefit to CoR removal. The Fe3O4/CS-PEI composite was effective for CoR removal in a wide pH range (3-13). Kinetics studies suggested that the adsorption mechanism of CoR followed the pseudo-second model and it was also affected by the boundary layer diffusion. The adsorption process followed the Redlich-Peterson isotherm equation. Thermodynamic studies also demonstrated that this adsorption process was spontaneous, favorable and endothermic. The activation energy (Ea) of the adsorption process was 34.08kJ/mol, indicating that chemisorption existed in the process. The results demonstrated that the porous magnetic Fe3O4/CS-PEI polymer composite is a promising adsorbent for the efficient removal of dye pollutants from aqueous solution. PMID- 28993298 TI - Microstructure and physical properties of nano-biocomposite films based on cassava starch and laponite. AB - The aim of this research was to study the effects of laponite concentrations on some properties of nano-biocomposite films based on cassava starch, focusing mainly the relation between the properties of the surface microstructure and roughness, water contact angle and gloss. Nano-biocomposite films were produced by casting. We analyzed gloss, color, opacity, water contact angle, crystallinity by X-ray diffraction, and microstructure by scanning electron microscopy and atomic force microscopy. Texture parameters (energy, entropy and fractal dimension) were extracted from micrographs. We observed a great impact of laponite in the morphology of nano-biocomposite films. Texture parameters correlated with surface heterogeneity and roughness. Finally, surface roughness affected the surface hydrophilicity of nano-biocomposite films. Laponite platelets were exfoliated and/or intercalated with amylose and amylopectin chains. This research reports new information on the effects of laponite concentrations on the morphological, optical and wetting properties of nano biocomposite films aiming future industrial applications. PMID- 28993300 TI - Analysis of isoniazid and rifampicin resistance in Mycobacterium tuberculosis isolates in Morocco using GenoType(r) MTBDRplus assay. AB - OBJECTIVES: The number of multidrug-resistant tuberculosis (MDR-TB) cases is rising worldwide. The present investigation aimed to evaluate, using the GenoType(r) MTBDRplus assay, the most common mutations associated with rifampicin (RIF) and isoniazid (INH) resistance among resistant strains in Morocco. METHODS: A total of 319 Mycobacterium tuberculosis isolates sent to the National Tuberculosis Reference Laboratory between 2013 and 2015 were subjected to GenoType(r) MTBDRplus for detecting M. tuberculosis and determination of drug susceptibility. Correlation of the minimum inhibitory concentrations (MICs) of INH with genotypic assay results was carried out for 97 MDR-TB strains. Various concentrations of INH were tested. RESULTS: The most frequent mutations observed were rpoBS531L (67.2%) and katGS315T1/2 (66.5%). Isolates with inhA gene mutation, katG gene mutation, and dual mutations in katG and inhA had MICs ranging from 0.5-1MUg/mL, 2-10MUg/mL and >=12MUg/mL, respectively. CONCLUSION: In Morocco, 66.5% and 76.7% of M. tuberculosis strains carried mutations causing high-level resistance to INH and RIF, respectively. PMID- 28993299 TI - Circulating microRNAs as a biomarker to predict therapy efficacy in hepatitis C patients with different genotypes. AB - BACKGROUND: Hepatitis C virus (HCV) genotype exerts a major influence on therapeutic response; however, the underlying mechanisms remain unclear. The aim of the study is to investigate the circulating microRNAs as the biomarkers to predict the response to therapy in chronic hepatitisC patients (HepC) with different genotypes. METHODS: HepC patients were separated into 4 groups by genotype, healthy individuals were enrolled as the control. microRNA-122 (miR 122), microRNA-155 (miR-155) and HCV RNA in serum and exosome were measured, associations between microRNAs, viral load and other conventional biomarkers were analyzed. RESULTS: Serum and exosomal HCV RNA in genotype 6a group was highest, followed by genotype 3a/2a, and in genotype 1b were the lowest. The significant correlations existed between exosomal HCV RNA and serum HCVRNA. MiR-122, both in serum (miR-122ser) and in exosome (miR-122exo), was higher in normal control than in HCV group. Specifically, miR-122exo were significantly higher in genotype 1b than other genotype groups (p < 0.05). On the contrary, miR-155exowas significantly lower in genotype 1b than in other groups (p < 0.05 for both). A strongly positive association was found between miR-122/155 and HCV viral load in patients with various genotypes. Higher miR-122ser at the start of therapy predicts a better outcome. CONCLUSIONS: Expression of miR-122/155 differ in each genotypes, miR-122ser could be independent factor affecting the therapy efficacy, which had higher diagnostic value in predicting HCV outcome. PMID- 28993301 TI - Using a UK Virtual Supermarket to Examine Purchasing Behavior Across Different Income Groups in the United Kingdom: Development and Feasibility Study. AB - BACKGROUND: The majority of food in the United Kingdom is purchased in supermarkets, and therefore, supermarket interventions provide an opportunity to improve diets. Randomized controlled trials are costly, time-consuming, and difficult to conduct in real stores. Alternative approaches of assessing the impact of supermarket interventions on food purchases are needed, especially with respect to assessing differential impacts on population subgroups. OBJECTIVE: The aim of this study was to assess the feasibility of using the United Kingdom Virtual Supermarket (UKVS), a three-dimensional (3D) computer simulation of a supermarket, to measure food purchasing behavior across income groups. METHODS: Participants (primary household shoppers in the United Kingdom with computer access) were asked to conduct two shopping tasks using the UKVS and complete questionnaires on demographics, food purchasing habits, and feedback on the UKVS software. Data on recruitment method and rate, completion of study procedure, purchases, and feedback on usability were collected to inform future trial protocols. RESULTS: A total of 98 participants were recruited, and 46 (47%) fully completed the study procedure. Low-income participants were less likely to complete the study (P=.02). Most participants found the UKVS easy to use (38/46, 83%) and reported that UKVS purchases resembled their usual purchases (41/46, 89%). CONCLUSIONS: The UKVS is likely to be a useful tool to examine the effects of nutrition interventions using randomized controlled designs. Feedback was positive from participants who completed the study and did not differ by income group. However, retention was low and needs to be addressed in future studies. This study provides purchasing data to establish sample size requirements for full trials using the UKVS. PMID- 28993302 TI - User Participation and Engagement With the See Me Smoke-Free mHealth App: Prospective Feasibility Trial. AB - BACKGROUND: The See Me Smoke-Free (SMSF) mobile health (mHealth) app was developed to help women quit smoking by targeting concerns about body weight, body image, and self-efficacy through cognitive behavioral techniques and guided imagery audio files addressing smoking, diet, and physical activity. A feasibility trial found associations between SMSF usage and positive treatment outcomes. This paper reports a detailed exploration of program use among eligible individuals consenting to study participation and completing the baseline survey (participants) and ineligible or nonconsenting app installers (nonparticipants), as well as the relationship between program use and treatment outcomes. OBJECTIVE: The aim of this study was to determine whether (1) participants were more likely to set quit dates, be current smokers, and report higher levels of smoking at baseline than nonparticipants; (2) participants opened the app and listened to audio files more frequently than nonparticipants; and (3) participants with more app usage had a higher likelihood of self-reported smoking abstinence at follow up. METHODS: The SMSF feasibility trial was a single arm, within-subjects, prospective cohort study with assessments at baseline and 30 and 90 days post enrollment. The SMSF app was deployed on the Google Play Store for download, and basic profile characteristics were obtained for all app installers. Additional variables were assessed for study participants. Participants were prompted to use the app daily during study participation. Crude differences in baseline characteristics between trial participants and nonparticipants were evaluated using t tests (continuous variables) and Fisher exact tests (categorical variables). Exact Poisson tests were used to assess group-level differences in mean usage rates over the full study period using aggregate Google Analytics data on participation and usage. Negative binomial regression models were used to estimate associations of app usage with participant baseline characteristics after adjustment for putative confounders. Associations between app usage and self-reported smoking abstinence were assessed using separate logistic regression models for each outcome measure. RESULTS: Participants (n=151) were more likely than nonparticipants (n=96) to report female gender (P<.02) and smoking in the 30 days before enrollment (P<.001). Participants and nonparticipants opened the app and updated quit dates at the same average rate (rate ratio [RR] 0.98; 95% CI 0.92-1.04; P=.43), but participants started audio files (RR 1.07; 95% CI 1.00-1.13; P<.04) and completed audio files (RR 1.11; 95% CI 1.03-1.18; P<.003) at significantly higher rates than nonparticipants. Higher app usage among participants was positively associated with some smoking cessation outcomes. CONCLUSIONS: This study suggests potential efficacy of the SMSF app, as increased usage was generally associated with higher self-reported smoking abstinence. A planned randomized controlled trial will assess the SMSF app's efficacy as an intervention tool to help women quit smoking. PMID- 28993303 TI - The Lived Experience of "Being Evaluated" for Organ Donation: Focus Groups with Living Kidney Donors. AB - BACKGROUND AND OBJECTIVES: Comprehensive evaluations are required to safeguard voluntarism and minimize harm to living kidney donors. This process is lengthy, invasive, and emotionally challenging, with up to one fifth of potential donors opting out. We aimed to describe donors' experiences of the evaluation process. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted 14 focus groups involving 123 kidney donors who completed donation from three transplant centers (Australia and Canada). Transcripts were analyzed thematically. RESULTS: We identified six themes reflecting donors' experiences of evaluation. The themes that related to perseverance included emotional investment (prioritizing the recipient's health, desperation for a normal life, protecting eligibility, shame of disappointing others, and overcoming opposition), undeterred by low risks (medical confidence and protection, worthwhile gamble, inherent invincibility, and normalizing risks), and mental preparation (avoiding regret, resolving decisional ambivalence, and managing expectations of recovery). The challenges included underlying fears for health (processing alarming information, unsettling uncertainty, and preoperative panic), system shortfalls (self-advocacy in driving the process, stressful urgency, inconsistent framing of safety, unnerving bodily scrutiny, questioning risk information, and draining finances); and lifestyle interference (living in limbo, onerous lifestyle disruption, and valuing flexibility). CONCLUSIONS: Previous donors described an emotional investment in donating and determination to protect their eligibility, despite having concerns for their health, financial and lifestyle disruption, and opposition from their family or community. Our findings suggest the need to prepare donors for surgery and recovery, minimize anxiety and lifestyle burdens, ensure that donors feel comfortable expressing their fears and concerns, reduce unnecessary delays, and make explicit the responsibilities of donors in their assessment process. PMID- 28993304 TI - Barriers and facilitators to integration of physician associates into the general practice workforce: a grounded theory approach. AB - BACKGROUND: Physician associates (PAs) are described as one solution to workforce capacity in primary care in the UK. Despite new investment in the role, how effective this will be in addressing unmet primary care needs is unclear. AIM: To investigate the barriers and facilitators to the integration of PAs into the general practice workforce. DESIGN AND SETTING: A modified grounded theory study in a region unfamiliar with the PA role. METHOD: No a priori themes were assumed. Themes generated from stakeholder interviews informed a literature review and theoretical framework, and were then tested in focus groups with GPs, advanced nurse practitioners (ANPs), and patients. Recorded data were transcribed verbatim, and organised using NVivo version 10.2.2, with iterative analysis of emergent themes. A reflexive diary and independent verification of coding and analysis were included. RESULTS: There were 51 participants (30 GPs, 11 ANPs, and 10 patients) in eight focus groups. GPs, ANPs, and patients recognised that support for general practice was needed to improve access. GPs expressed concerns regarding PAs around managing medical complexity and supervision burden, non prescriber status, and medicolegal implications in routine practice. Patients were less concerned about specific competencies as long as there was effective supervision, and were accepting of a PA role. ANPs highlighted their own negative experiences entering advanced clinical practice, and the need for support to counteract stereotypical and prejudicial attitudes CONCLUSION: This study highlights the complex factors that may impede the introduction of PAs into UK primary care. A conceptual model is proposed to help regulators and educationalists support this integration, which has relevance to other proposed new roles in primary care. PMID- 28993305 TI - Effectiveness of UK provider financial incentives on quality of care: a systematic review. AB - BACKGROUND: Provider financial incentives are being increasingly adopted to help improve standards of care while promoting efficiency. AIM: To review the UK evidence on whether provider financial incentives are an effective way of improving the quality of health care. DESIGN AND SETTING: Systematic review of UK evidence, undertaken in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. METHOD: MEDLINE and Embase databases were searched in August 2016. Original articles that assessed the relationship between UK provider financial incentives and a quantitative measure of quality of health care were included. Studies showing improvement for all measures of quality of care were defined as 'positive', those that were 'intermediate' showed improvement in some measures, and those classified as 'negative' showed a worsening of measures. Studies showing no effect were documented as such. Quality was assessed using the Downs and Black quality checklist. RESULTS: Of the 232 published articles identified by the systematic search, 28 were included. Of these, nine reported positive effects of incentives on quality of care, 16 reported intermediate effects, two reported no effect, and one reported a negative effect. Quality assessment scores for included articles ranged from 15 to 19, out of a maximum of 22 points. CONCLUSION: The effects of UK provider financial incentives on healthcare quality are unclear. Owing to this uncertainty and their significant costs, use of them may be counterproductive to their goal of improving healthcare quality and efficiency. UK policymakers should be cautious when implementing these incentives - if used, they should be subject to careful long-term monitoring and evaluation. Further research is needed to assess whether provider financial incentives represent a cost-effective intervention to improve the quality of care delivered in the UK. PMID- 28993306 TI - Experiences with online consultation systems in primary care: case study of one early adopter site. AB - BACKGROUND: There is a strong policy drive towards implementing alternatives to face-to-face consultations in general practice to improve access, efficiency, and cost-effectiveness. These alternatives embrace novel technologies that are assumed to offer potential to improve care. AIM: To explore the introduction of one online consultation system (Tele-Doc) and how it shapes working practices. DESIGN AND SETTING: Mixed methods case study in an inner-city general practice. METHOD: The study was conducted through interviews with IT developers, clinicians, and administrative staff, and scrutiny of documents, websites, and demonstrator versions of Tele-Doc, followed by thematic analysis and discourse analysis. RESULTS: Three interrelated themes were identified: online consultation systems as innovation, managing the 'messiness' of general practice consultations, and redistribution of the work of general practice. These themes raise timely questions about what it means to consult in contemporary general practice. Uptake of Tele-Doc by patients was low. Much of the work of the consultation was redistributed to patients and administrators, sometimes causing misunderstandings. The 'messiness' of consultations was hard to eliminate. In house training focused on the technical application rather than associated transformations to practice work that were not anticipated. GPs welcomed varied modes of consulting, but the aspiration of improved efficiency was not realised in practice. CONCLUSION: Tele-Doc offers a new kind of consultation that is still being worked out in practice. It may offer convenience for patients with discrete, single problems, and a welcome variation to GPs' workload. Tele-Doc's potential for addressing more complex problems and achieving efficiency is less clear, and its adoption may involve unforeseeable consequences. PMID- 28993307 TI - Improving access to allied health professionals through the Champlain BASETM eConsult service: a cross-sectional study in Canada. AB - BACKGROUND: Allied health services are an important part of providing effective team-based care. The Champlain BASETM (Building Access to Specialists through eConsultation) eConsult service facilitates quick and secure communication between primary care providers (PCPs) and allied health professionals (AHPs). AIM: To assess the eConsult service's ability to improve access to advice from AHPs. DESIGN AND SETTING: A cross-sectional study was carried out on all cases submitted to AHPs through the eConsult service between April 2011 and May 2016. The service covers Ottawa, Canada, and its surrounding rural communities. METHOD: A descriptive overview of all cases submitted to allied health services was conducted. Utilisation and survey metrics for AHP eConsults were compared with those sent to medical specialties, in order to understand the potential differences and generalisability of eConsult access beyond the traditional medical specialty referral. RESULTS: PCPs submitted 127 cases to nine allied health specialties during the study period. The most popular specialty was clinical pharmacist, which received an average of 1.5 cases per month. The median specialist response time was 2.1 days (interquartile range [IQR] 0.7-5.3 days, range 0.01-14.2 days) versus 0.9 days (IQR 0.2-3.4 days, range 0-49.5 days) for medical specialties. PCPs received advice for a new or additional course of action in 70% (versus 58% for medical specialties) of cases. They rated the service as being of high or very high value for their patients in 88% of cases (versus 93% for medical specialties), and for themselves in 89% (94% for medical specialties) of cases. CONCLUSION: The eConsult service has demonstrated the ability to support prompt communication between PCPs and AHPs, improving patients' access to AHP care. Given the importance of AHPs in providing primary care, allied health services should be offered in the menu of specialties available through electronic consultation services. PMID- 28993308 TI - Safe handover. PMID- 28993309 TI - Clinical peer review of GP referrals might be construed as peer pressure. PMID- 28993313 TI - Checkpoint Inhibitors Spur Changes in Trial Design. AB - Given the success of checkpoint inhibitors and the desire to test them in combination with other immunotherapies and targeted therapies, hundreds of clinical trials have been launched. To most efficiently study these agents, researchers and the FDA are exploring the use of novel endpoints, the use of new preclinical models, and adaptive trial designs. However, the cost and demands associated with the conduct of increasingly sophisticated early-phase clinical trials are putting smaller companies and some academic medical centers at a disadvantage. PMID- 28993312 TI - MMP-14 overexpression correlates with the neurodegenerative process in familial amyloidotic polyneuropathy. AB - Levels of matrix metalloproteases (MMPs) can be differentially regulated in response to injury or neurological diseases. For instance, it is known that selective and short-term inhibition of MMP-14, a membrane-type 1 MMP, accelerates axon regeneration. Because axon growth and regeneration is impaired in familial amyloidotic polyneuropathy (FAP), a neurodegenerative disorder characterized by misfolding and deposition of mutant transthyretin (TTR) in the peripheral nervous system (PNS), we presently investigated the expression levels and the potential role for MMP-14 in this condition. By using cell culture studies, a mouse model of disease and human clinical samples, we observed that MMP-14: (i) is overexpressed in FAP nerves, correlating with TTR deposition; (ii) is upregulated in sciatic nerves from a preclinical transgenic mouse model, increasing with TTR deposition; (iii) levels in the PNS and plasma are rescued upon treatment of mice with anakinra or TTR siRNA, drugs acting over the IL-1 signaling pathway or TTR liver synthesis, respectively; (iv) increases in Schwann cells upon incubation with amyloid-like aggregates; and, finally, (v) is increased in plasma of FAP patients, correlating with disease progression. These results highlight the relevance of MMP-14 in the pathophysiology of FAP, suggesting not only a potential role for this molecule as a novel biomarker for therapy follow up, but also as a new potential therapeutic target. PMID- 28993315 TI - Fear of missing out on conferences. PMID- 28993316 TI - Father loses appeal for L1m damages against IVF clinic to raise daughter. PMID- 28993314 TI - Mecp2 regulates tnfa during zebrafish embryonic development and acute inflammation. AB - Mutations in MECP2 cause Rett syndrome, a severe neurological disorder with autism-like features. Duplication of MECP2 also causes severe neuropathology. Both diseases display immunological abnormalities that suggest a role for MECP2 in controlling immune and inflammatory responses. Here, we used mecp2-null zebrafish to study the potential function of Mecp2 as an immunological regulator. Mecp2 deficiency resulted in an increase in neutrophil infiltration and upregulated expression of the pro- and anti-inflammatory cytokines Il1b and Il10 as a secondary response to disturbances in tissue homeostasis. By contrast, expression of the proinflammatory cytokine tumor necrosis factor alpha (Tnfa) was consistently downregulated in mecp2-null animals during development, representing the earliest developmental phenotype described for MECP2 deficiency to date. Expression of tnfa was unresponsive to inflammatory stimulation, and was partially restored by re-expression of functional mecp2 Thus, Mecp2 is required for tnfa expression during zebrafish development and inflammation. Finally, RNA sequencing of mecp2-null embryos revealed dysregulated processes predictive for Rett syndrome phenotypes. PMID- 28993318 TI - Junior doctor is struck off after trying to arrange sex with minor. PMID- 28993317 TI - Proportionate methods for evaluating a simple digital mental health tool. AB - BACKGROUND: Traditional evaluation methods are not keeping pace with rapid developments in mobile health. More flexible methodologies are needed to evaluate mHealth technologies, particularly simple, self-help tools. One approach is to combine a variety of methods and data to build a comprehensive picture of how a technology is used and its impact on users. OBJECTIVE: This paper aims to demonstrate how analytical data and user feedback can be triangulated to provide a proportionate and practical approach to the evaluation of a mental well-being smartphone app (In Hand). METHODS: A three-part process was used to collect data: (1) app analytics; (2) an online user survey and (3) interviews with users. FINDINGS: Analytics showed that >50% of user sessions counted as 'meaningful engagement'. User survey findings (n=108) revealed that In Hand was perceived to be helpful on several dimensions of mental well-being. Interviews (n=8) provided insight into how these self-reported positive effects were understood by users. CONCLUSIONS: This evaluation demonstrates how different methods can be combined to complete a real world, naturalistic evaluation of a self-help digital tool and provide insights into how and why an app is used and its impact on users' well being. CLINICAL IMPLICATIONS: This triangulation approach to evaluation provides insight into how well-being apps are used and their perceived impact on users' mental well-being. This approach is useful for mental healthcare professionals and commissioners who wish to recommend simple digital tools to their patients and evaluate their uptake, use and benefits. PMID- 28993319 TI - Sixty seconds on . . . NHS Property Services. PMID- 28993320 TI - Retraction. PMID- 28993311 TI - Central and peripheral circadian clocks and their role in Alzheimer's disease. AB - Molecular and cellular oscillations constitute an internal clock that tracks the time of day and permits organisms to optimize their behaviour and metabolism to suit the daily demands they face. The workings of this internal clock become impaired with age. In this review, we discuss whether such age-related impairments in the circadian clock interact with age-related neurodegenerative disorders, such as Alzheimer's disease. Findings from mouse and fly models of Alzheimer's disease have accelerated our understanding of the interaction between neurodegeneration and circadian biology. These models show that neurodegeneration likely impairs circadian rhythms either by damaging the central clock or by blocking its communication with other brain areas and with peripheral tissues. The consequent sleep and metabolic deficits could enhance the susceptibility of the brain to further degenerative processes. Thus, circadian dysfunction might be both a cause and an effect of neurodegeneration. We also discuss the primary role of light in the entrainment of the central clock and describe important, alternative time signals, such as food, that play a role in entraining central and peripheral circadian clocks. Finally, we propose how these recent insights could inform efforts to develop novel therapeutic approaches to re-entrain arrhythmic individuals with neurodegenerative disease. PMID- 28993321 TI - Figures show big increase in outstanding general practice premises fees. PMID- 28993310 TI - Rodent models in Down syndrome research: impact and future opportunities. AB - Down syndrome is caused by trisomy of chromosome 21. To date, a multiplicity of mouse models with Down-syndrome-related features has been developed to understand this complex human chromosomal disorder. These mouse models have been important for determining genotype-phenotype relationships and identification of dosage sensitive genes involved in the pathophysiology of the condition, and in exploring the impact of the additional chromosome on the whole genome. Mouse models of Down syndrome have also been used to test therapeutic strategies. Here, we provide an overview of research in the last 15 years dedicated to the development and application of rodent models for Down syndrome. We also speculate on possible and probable future directions of research in this fast-moving field. As our understanding of the syndrome improves and genome engineering technologies evolve, it is necessary to coordinate efforts to make all Down syndrome models available to the community, to test therapeutics in models that replicate the whole trisomy and design new animal models to promote further discovery of potential therapeutic targets. PMID- 28993323 TI - Letter to the editor: Comments on Wette et al. (2017): "Characterization of muscle ankyrin repeat proteins in human skeletal muscle". PMID- 28993324 TI - Reply to "Letter to the editor: Comments on Wette et al. (2017): 'Characterization of muscle ankyrin repeat proteins in human skeletal muscle'". PMID- 28993325 TI - CORRIGENDUM. PMID- 28993322 TI - Comparative study of expression and activity of glucose transporters between stem cell-derived brain microvascular endothelial cells and hCMEC/D3 cells. AB - Glucose constitutes a major source of energy of mammalian brains. Glucose uptake at the blood-brain barrier (BBB) occurs through a facilitated glucose transport, through glucose transporter 1 (GLUT1), although other isoforms have been described at the BBB. Mutations in GLUT1 are associated with the GLUT1 deficiency syndrome, yet none of the current in vitro models of the human BBB maybe suited for modeling such a disorder. In this study, we investigated the expression of glucose transporters and glucose diffusion across brain microvascular endothelial cells (BMECs) derived from healthy patient-derived induced pluripotent stem cells (iPSCs). We investigated the expression of different glucose transporters at the BBB using immunocytochemistry and flow cytometry and measured glucose uptake and diffusion across BMEC monolayers obtained from two iPSC lines and from hCMEC/D3 cells. BMEC monolayers showed expression of several glucose transporters, in particular GLUT1, GLUT3, and GLUT4. Diffusion of glucose across the monolayers was mediated via a saturable transcellular mechanism and partially inhibited by pharmacological inhibitors. Taken together, our study suggests the presence of several glucose transporters isoforms at the human BBB and demonstrates the feasibility of modeling glucose across the BBB using patient-derived stem cells. PMID- 28993326 TI - A Dynamic Stress Model Explains the Delayed Drug Effect in Artemisinin Treatment of Plasmodium falciparum. AB - Artemisinin resistance constitutes a major threat to the continued success of control programs for malaria, particularly in light of developing resistance to partner drugs. Improving our understanding of how artemisinin-based drugs act and how resistance manifests is essential for the optimization of dosing regimens and the development of strategies to prolong the life span of current first-line treatment options. Recent short-drug-pulse in vitro experiments have shown that the parasite killing rate depends not only on drug concentration but also the exposure time, challenging the standard pharmacokinetic-pharmacodynamic (PK-PD) paradigm in which the killing rate depends only on drug concentration. Here, we introduce a dynamic stress model of parasite killing and show through application to 3D7 laboratory strain viability data that the inclusion of a time-dependent parasite stress response dramatically improves the model's explanatory power compared to that of a traditional PK-PD model. Our model demonstrates that the previously reported hypersensitivity of early-ring-stage parasites of the 3D7 strain to dihydroartemisinin compared to other parasite stages is due primarily to a faster development of stress rather than a higher maximum achievable killing rate. We also perform in vivo simulations using the dynamic stress model and demonstrate that the complex temporal features of artemisinin action observed in vitro have a significant impact on predictions for in vivo parasite clearance. Given the important role that PK-PD models play in the design of clinical trials for the evaluation of alternative drug dosing regimens, our novel model will contribute to the further development and improvement of antimalarial therapies. PMID- 28993327 TI - In Vitro Activities of Pexiganan and 10 Comparator Antimicrobials against 502 Anaerobic Isolates Recovered from Skin and Skin Structure Infections. AB - Pexiganan, a cationic peptide, exhibited a broad range of anti-anaerobic antimicrobial activity. The MIC90s of studied isolates were as follows: Bacteroides fragilis, 16 MUg/ml; other B. fragilis group spp., 4 MUg/ml; Prevotella and Fusobacterium spp., 32 MUg/ml; Porphyromonas spp., 64 MUg/ml; Propionibacterium acnes, 4 MUg/ml; Eggerthella lenta and Peptostreptococcus anaerobius, 32 MUg/ml; other Gram-positive rods and cocci, 4 MUg/ml; Clostridium perfringens, 128 MUg/ml; and other clostridia, 256 MUg/ml. Pexiganan cream shows potential as adjunctive therapy for skin and skin structure infections (SSSIs) involving anaerobes. PMID- 28993329 TI - Inhibition of Fosfomycin Resistance Protein FosA by Phosphonoformate (Foscarnet) in Multidrug-Resistant Gram-Negative Pathogens. AB - FosA proteins confer fosfomycin resistance to Gram-negative pathogens via glutathione-mediated modification of the antibiotic. In this study, we assessed whether inhibition of FosA by sodium phosphonoformate (PPF) (foscarnet), a clinically approved antiviral agent, would reverse fosfomycin resistance in representative Gram-negative pathogens. The inhibitory activity of PPF against purified recombinant FosA from Escherichia coli (FosA3), Klebsiella pneumoniae (FosAKP), Enterobacter cloacae (FosAEC), and Pseudomonas aeruginosa (FosAPA) was determined by steady-state kinetic measurements. The antibacterial activity of PPF against FosA in clinical strains of these species was evaluated by susceptibility testing and time-kill assays. PPF increased the Michaelis constant (Km ) for fosfomycin in a dose-dependent manner, without affecting the maximum rate (Vmax) of the reaction, for all four FosA enzymes tested, indicating a competitive mechanism of inhibition. Inhibitory constant (Ki ) values were 22.6, 35.8, 24.4, and 56.3 MUM for FosAKP, FosAEC, FosAPA, and FosA3, respectively. Addition of clinically achievable concentrations of PPF (~667 MUM) reduced the fosfomycin MICs by >=4-fold among 52% of the K. pneumoniae, E. cloacae, and P. aeruginosa clinical strains tested and led to a bacteriostatic or bactericidal effect in time-kill assays among representative strains. PPF inhibits FosA activity across Gram-negative species and can potentiate fosfomycin activity against the majority of strains with chromosomally encoded fosA These data suggest that PPF may be repurposed as an adjuvant for fosfomycin to treat infections caused by some FosA-producing, multidrug-resistant, Gram-negative pathogens. PMID- 28993328 TI - Molecular Characterization of Carbapenemase-Producing Pseudomonas aeruginosa of Czech Origin and Evidence for Clonal Spread of Extensively Resistant Sequence Type 357 Expressing IMP-7 Metallo-beta-Lactamase. AB - The objective of this study was to perform molecular surveillance for assessing the spread of carbapenemase-producing Pseudomonas aeruginosa in Czech hospitals. One hundred thirty-six carbapenemase-producing isolates were recovered from 22 hospitals located throughout the country. Sequence type 357 (ST357) dominated (n = 120) among carbapenemase producers. One hundred seventeen isolates produced IMP type (IMP-7 [n = 116] and IMP-1 [n = 1]) metallo-beta-lactamases (MbetaLs), 15 produced the VIM-2 MbetaL, and the remaining isolates expressed the GES-5 enzyme. The blaIMP-like genes were located in three main integron types, with In-p110 like being the most prevalent (n = 115). The two other IMP-encoding integrons (In1392 and In1393) have not been described previously. blaVIM-2-carrying integrons included In59-like, In56, and a novel element (In1391). blaGES-5 was carried by In717. Sequencing data showed that In-p110-like was associated with a Tn4380-like transposon inserted in genomic island LESGI-3 in the P. aeruginosa chromosome. The other integrons were also integrated into the P. aeruginosa chromosome. These findings indicated the clonal spread of ST357 P. aeruginosa, carrying the IMP-7-encoding integron In-p110, in Czech hospitals. Additionally, the sporadic emergence of P. aeruginosa producing different carbapenemase types, associated with divergent or novel integrons, punctuated the ongoing evolution of these bacteria. PMID- 28993330 TI - Impact of Morphological Sectors on Antifungal Susceptibility Testing and Virulence Studies. AB - Morphological heterogeneity of Aspergillus terreus cultures was observed during continued cultivation of amphotericin B (AMB)-resistant isolates on drug-free medium. Outgrowth leads to the emergence of multiple sectors that might result from increased growth rates at drug-free conditions. We evaluated the differences in AMB susceptibility and virulence between sector subcultures (ATSec), AMB resistant (ATR) strains, and AMB-susceptible (ATS) strains. By comparing A. terreus AMB-resistant (ATR) strains and A. terreus sector (ATSec) cultures we observed a highly significant reduction of AMB MICs in ATSec (ATR MIC, 2 to 32 MUg/ml; ATSec MIC, 0.12 to 5 MUg/ml). Furthermore, Galleria mellonella survival studies revealed an enhanced virulence of ATSec, which was comparable with that of AMB-sensitive Aspergillus terreus strains (median survival rates for ATS isolates, 72 h; for ATSec isolate ATSecG1, 84 h; for ATR isolates, 144 h). Our findings clearly demonstrate that spontaneous culture degeneration occurs in A. terreus and, most importantly, crucially impacts drug efficacy and virulence. PMID- 28993331 TI - Evaluation of Pharmacokinetic/Pharmacodynamic Model-Based Optimized Combination Regimens against Multidrug-Resistant Pseudomonas aeruginosa in a Murine Thigh Infection Model by Using Humanized Dosing Schemes. AB - We previously optimized imipenem and tobramycin combination regimens against a double-resistant clinical Pseudomonas aeruginosa isolate by using in vitro infection models, mechanism-based pharmacokinetic/pharmacodynamic modeling (MBM), and Monte Carlo simulations. The current study aimed to evaluate these regimens in a neutropenic murine thigh infection model and to characterize the time course of bacterial killing and regrowth via MBM. We studied monotherapies and combinations of imipenem with tobramycin in vivo against the double-resistant clinical P. aeruginosa isolate by using humanized dosing schemes. Viable count profiles of total and resistant populations were quantified over 24 h. Tobramycin monotherapy (7 mg/kg every 24 h [q24h] as a 0.5-h infusion) was ineffective. Imipenem monotherapies (continuous infusion of 4 or 5 g/day with a 1-g loading dose) yielded 2.47 or 2.57 log10 CFU/thigh killing at 6 h. At 24 h, imipenem at 4 g/day led to regrowth up to the initial inoculum (4.79 +/- 0.26 log10 CFU/thigh), whereas imipenem at 5 g/day displayed 1.75 log10 killing versus the initial inoculum. The combinations (i.e., imipenem at 4 or 5 g/day plus tobramycin) provided a clear benefit, with bacterial killing of >=2.51 or >=1.50 log10 CFU/thigh compared to the respective most active monotherapy at 24 h. No colonies were detected on 3*MIC agar plates for combinations, whereas increased resistance (at 3*MIC) emerged for monotherapies (except imipenem at 5 g/day). MBM suggested that tobramycin considerably enhanced the imipenem target site concentration up to 2.6-fold. The combination regimens, rationally optimized via a translational modeling approach, demonstrated substantially enhanced bacterial killing and suppression of regrowth in vivo against a double-resistant isolate and are therefore promising for future clinical evaluation. PMID- 28993332 TI - Amikacin Pharmacokinetics To Optimize Dosing in Neonates with Perinatal Asphyxia Treated with Hypothermia. AB - Aminoglycoside pharmacokinetics (PK) is expected to change in neonates with perinatal asphyxia treated with therapeutic hypothermia (PATH). Several amikacin dosing guidelines have been proposed for treating neonates with (suspected) septicemia; however, none provide adjustments for cases of PATH. Therefore, we aimed to quantify the differences in amikacin PK between neonates with and without PATH to propose suitable dosing recommendations. Based on amikacin therapeutic drug monitoring data collected retrospectively from neonates with PATH, combined with a published data set, we assessed the impact of PATH on amikacin PK by using population modeling. Monte Carlo and stochastic simulations were performed to establish amikacin exposures in neonates with PATH after dosing according to the current guidelines and according to proposed model-derived dosing guidelines. Amikacin clearance was decreased 40.6% in neonates with PATH, with no changes in volume of distribution. Simulations showed that increasing the dosing interval by 12 h results in a decrease in the percentage of neonates reaching toxic trough levels (>5 mg/liter), from 40 to 76% to 14 to 25%, while still reaching efficacy targets compared to the results of current dosing regimens. Based on this study, a 12-h increase in the amikacin dosing interval in neonates with PATH is proposed to correct for the reduced clearance, yielding safe and effective exposures. As amikacin is renally excreted, further studies into other renally excreted drugs may be required, as their clearance may also be impaired. PMID- 28993334 TI - Choosing Optimal Antifungal Agents To Prevent Fungal Infections in Nonneutropenic Critically Ill Patients: Trial Sequential Analysis, Network Meta-analysis, and Pharmacoeconomic Analysis. AB - The use of antifungal interventions in critically ill patients prior to invasive fungal infection (IFI) being microbiologically confirmed and the preferred drug are still controversial. A systematic literature search was performed to identify randomized controlled trials (RCTs) that compared untargeted antifungal treatments applied to nonneutropenic critically ill patients. The primary outcomes were all-cause mortality and proven IFI rates. A random-effects model was used with trial sequential analyses (TSA), a network meta-analysis (NMA) was conducted to obtain indirect evidence, and a cost-effectiveness analysis using a decision-analytic model was completed from the patient perspective over a lifetime horizon. In total, 19 RCTs involving 2,556 patients (7 interventions) were included. Untargeted antifungal treatment did not significantly decrease the incidence of all-cause mortality (odds ratio [OR] = 0.89, 95% confidence interval [95%CI] = 0.70 to 1.14), but it did reduce the incidence of proven IFI (OR = 0.45, 95%CI = 0.29 to 0.71) relative to placebo/no intervention. The TSA showed that there was sufficient evidence supporting these findings. In the NMA, the only significant difference found for both primary outcomes was between fluconazole and placebo/no intervention in preventing proven IFI (OR = 0.35, 95%CI = 0.19 to 0.65). Based on drug and hospital costs in China, the incremental cost-effectiveness ratios per life-year saved for fluconazole, caspofungin, and micafungin relative to placebo/no intervention corresponded to US$889, US$9,994, and US$10,351, respectively. Untargeted antifungal treatment significantly reduced proven IFI rates in nonneutropenic critically ill patients but with no mortality benefits relative to placebo/no intervention. Among the well-tolerated antifungals, fluconazole remains the only one that is effective for IFI prevention and significantly cheaper than echinocandins. PMID- 28993333 TI - Antibiotics Promote Escherichia coli-Pseudomonas aeruginosa Conjugation through Inhibiting Quorum Sensing. AB - The effect of antibiotics on horizontal gene transfer (HGT) is controversial, and the underlying mechanism remains poorly understood. Here, using Escherichia coli SM10lambdapi as the donor strain, which carries a chromosomally integrated RP4 plasmid, we investigated the effect of antibiotics on conjugational transfer of a mobilizable gentamicin (Gm) resistance plasmid. The results showed that an exposure to gentamicin that restricted the survival of recipient cells significantly enhanced SM10lambdapi-Pseudomonas aeruginosa PAO1 conjugation, which was attenuated by a deficiency of lasI-rhlI, genes associated with the generation of the quorum sensing signals N-acyl homoserine lactones (AHLs) in PAO1, or the deletion of the AHL receptor SdiA in SM10lambdapi. Subsequent mechanistic investigations revealed that a treatment with Gm repressed the mRNA expression of lasI and rhlI in PAO1 and upregulated traI expression in SM10lambdapi. Moreover, PAO1 treated with other quorum sensing (QS)-inhibiting antibiotics such as azithromycin or chloramphenicol also showed a conjugation promoting ability. On the other hand, when using non-AHL-producing E. coli strain EC600 as the recipient cells, the promoting effect of Gm on conjugation could not be observed. These data suggest that AHL-SdiA contributes to the effectiveness of antibiotics on plasmid conjugation. Collectively, our findings highlight the HGT promoting effect of antibiotics and suggest quorum sensing as a promising target for controlling antibiotic resistance dissemination. These findings have implications for assessing the risks of antibiotic use and developing advisable antibiotic treatment protocols. PMID- 28993335 TI - Effects of Maraviroc versus Efavirenz in Combination with Zidovudine-Lamivudine on the CD4/CD8 Ratio in Treatment-Naive HIV-Infected Individuals. AB - A low CD4/CD8 ratio during treated HIV infection reflects heightened immune activation and predicts death. The effects of different antiretroviral therapy regimens on CD4/CD8 ratio recovery remains unclear. We performed a post hoc analysis of the MERIT study, a randomized, double-blind trial of maraviroc versus efavirenz in combination with zidovudine-lamivudine in treatment-naive HIV infected individuals. We found higher rates of CD4/CD8 ratio normalization with efavirenz, which was driven by a greater CD8+ T-cell decline. PMID- 28993336 TI - Emergence of Various NDM-Type-Metallo-beta-Lactamase-Producing Escherichia coli Clinical Isolates in Nepal. AB - Of 250 clinical isolates of Escherichia coli obtained in Nepal, 38 were carbapenem resistant, with MICs of imipenem or meropenem of >=4 MUg/ml. All 38 isolates harbored the following blaNDMs: blaNDM-1, blaNDM-3, blaNDM-4, blaNDM-5, blaNDM-7, blaNDM-12, and blaNDM-13 Most of these isolates also harbored the 16S rRNA methylase gene(s) armA, rmtB, and/or rmtC. PMID- 28993338 TI - Activity of Ceftolozane-Tazobactam and Ceftazidime-Avibactam against Beta-Lactam Resistant Pseudomonas aeruginosa Isolates. AB - Ceftolozane-tazobactam (C/T) and ceftazidime-avibactam (CZA) MICs were evaluated for a collection of 309 beta-lactam-resistant isolates of Pseudomonas aeruginosa recovered from three institutions in the area of Los Angeles, CA. Overall, 12.0% of isolates were susceptible to imipenem, 15.9% were susceptible to meropenem, 20.7% were susceptible to piperacillin-tazobactam, 24.6% were susceptible to ceftazidime, 25.9% were susceptible to cefepime, 72.5% were susceptible to C/T, and 61.8% were susceptible to CZA. Among C/T-resistant isolates, 9.1% were CZA susceptible, whereas 36.4% of CZA-resistant isolates were susceptible to C/T. PMID- 28993340 TI - Erratum. DDB1-Mediated CRY1 Degradation Promotes FOXO1-Driven Gluconeogenesis in Liver. Diabetes 2017;66:2571-2582. PMID- 28993337 TI - Whole-Transcriptome and -Genome Analysis of Extensively Drug-Resistant Mycobacterium tuberculosis Clinical Isolates Identifies Downregulation of ethA as a Mechanism of Ethionamide Resistance. AB - Genetics-based drug susceptibility testing has improved the diagnosis of drug resistant tuberculosis but is limited by our lack of knowledge of all resistance mechanisms. Next-generation sequencing has assisted in identifying the principal genetic mechanisms of resistance for many drugs, but a significant proportion of phenotypic drug resistance is unexplained genetically. Few studies have formally compared the transcriptomes of susceptible and resistant Mycobacterium tuberculosis strains. We carried out comparative whole-genome transcriptomics of extensively drug-resistant (XDR) clinical isolates using RNA sequencing (RNA-seq) to find novel transcription-mediated mechanisms of resistance. We identified a promoter mutation (t to c) at position -11 (t-11c) relative to the start codon of ethA that reduces the expression of a monooxygenase (EthA) that activates ethionamide. (In this article, nucleotide changes are lowercase and amino acid substitutions are uppercase.) Using a flow cytometry-based reporter assay, we show that the reduced transcription of ethA is not due to transcriptional repression by ethR Clinical strains harboring this mutation were resistant to ethionamide. Other ethA promoter mutations were identified in a global genomic survey of resistant M. tuberculosis strains. These results demonstrate a new mechanism of ethionamide resistance that can cause high-level resistance when it is combined with other ethionamide resistance-conferring mutations. Our study revealed many other genes which were highly up- or downregulated in XDR strains, including a toxin-antitoxin module (mazF5 mazE5) and tRNAs (leuX and thrU). This suggests that global transcriptional modifications could contribute to resistance or the maintenance of bacterial fitness have also occurred in XDR strains. PMID- 28993339 TI - The Alternative Sigma Factors SigE and SigB Are Involved in Tolerance and Persistence to Antitubercular Drugs. AB - The emergence and spread of drug-resistant Mycobacterium tuberculosis strains possibly threaten our ability to treat this disease in the future. Even though two new antitubercular drugs have recently been introduced, there is still the need to design new molecules whose mechanisms of action could reduce the length of treatment. We show that two alternative sigma factors of M. tuberculosis (SigE and SigB) have a major role in determining the level of basal resistance to several drugs and the amount of persisters surviving long-duration drug treatment. We also demonstrate that ethambutol, a bacteriostatic drug, is highly bactericidal for M. tuberculosis mutants missing either SigE or SigB. We suggest that molecules able to interfere with the activity of SigE or SigB not only could reduce M. tuberculosis virulence in vivo but also could boost the effect of other drugs by increasing the sensitivity of the organism and reducing the number of persisters able to escape killing. PMID- 28993341 TI - Insights From Molecular Characterization of Adult Patients of Families With Multigenerational Diabetes. AB - Multigenerational diabetes of adulthood is a mostly overlooked entity, simplistically lumped into the large pool of type 2 diabetes. The general aim of our research in the past few years is to unravel the genetic causes of this form of diabetes. Identifying among families with multigenerational diabetes those who carry mutations in known monogenic diabetes genes is the first step to then allow us to concentrate on remaining pedigrees in which to unravel new diabetes genes. Targeted next-generation sequencing of 27 monogenic diabetes genes was carried out in 55 family probands and identified mutations verified among their relatives by Sanger sequencing. Nine variants (in eight probands) survived our filtering/prioritization strategy. After likelihood of causality assessment by established guidelines, six variants were classified as "pathogenetic/likely pathogenetic" and two as "of uncertain significance." Combining present results with our previous data on the six genes causing the most common forms of maturity onset diabetes of the young allows us to infer that 23.6% of families with multigenerational diabetes of adulthood carry mutations in known monogenic diabetes genes. Our findings indicate that the genetic background of hyperglycemia is unrecognized in the vast majority of families with multigenerational diabetes of adulthood. These families now become the object of further research aimed at unraveling new diabetes genes. PMID- 28993343 TI - Statins in systemic lupus erythematosus. PMID- 28993342 TI - In Vivo Detection of HSP90 Identifies Breast Cancers with Aggressive Behavior. AB - Purpose: Hsp90, a chaperone to numerous molecular pathways in malignant cells, is elevated in aggressive breast cancers. We hypothesized that identifying breast cells with elevated Hsp90 activity in situ could result in early detection of aggressive breast cancers.Experimental Design: We exploited the uptake of an Hsp90 inhibitor by malignant cells to create an imaging probe (HS131) of Hsp90 activity by linking it to a near-infrared (nIR) dye. HS131 uptake into cells correlated with cell membrane expression of Hsp90 and was used to image molecular subtypes of murine and human breast cancers in vitro and in murine models.Results: HS131 imaging was both sensitive and specific in detecting the murine 4T1 breast cancer cell line, as well as subclones with differing metastatic potential. Highly metastatic subclones (4T07) had high HS131 uptake, but subclones with lower metastatic potential (67NR, 168FARN) had low HS131 uptake. We generated isogenic cell lines to demonstrate that overexpression of a variety of specific oncogenes resulted in high HS131 uptake and retention. Finally, we demonstrated that HS131 could be used to detect spontaneous tumors in MMTV-neu mice, as well as primary and metastatic human breast cancer xenografts. HS131 could image invasive lobular breast cancer, a histologic subtype of breast cancer which is often undetectable by mammography.Conclusions: An HSP90-targeting nIR probe is sensitive and specific in imaging all molecular subtypes of murine and human breast cancer, with higher uptake in aggressive and highly metastatic clones. Clinical studies with Hsp90-targeting nIR probes will be initiated shortly. Clin Cancer Res; 23(24); 7531-42. (c)2017 AACR. PMID- 28993344 TI - Chondroitin sulfate is superior to placebo in symptomatic knee osteoarthritis. PMID- 28993345 TI - Response to eLetter: 'Discussion of methotrexate dosage' by Maguire et al. PMID- 28993347 TI - Interrupted aortic arch complicated with takotsubo cardiomyopathy mimicking aortic dissection. AB - A 50-year-old man presented to the emergency department with interscapular pain, diaphoresis and restlessness. Initial examination raised the possibility of aortic dissection; however, the CT scan did not concur with the diagnosis. An ECG showed ST segment elevation in leads V1-V6 and echocardiography showed severe left ventricular systolic dysfunction. Coronary angiography through the right femoral artery was attempted but the diagnostic catheter could not be advanced to the ascending aorta. Radiocontrast injection showed complete obstruction of the descending aorta. Coronary angiography through right radial approach showed mild left anterior descending disease. The aortogram showed complete interruption of the ascending aorta with extensive collateral network. Left ventricle gram was consistent with stress-induced cardiomyopathy. We noticed intermittent confusion and agitation. MRI of the brain showed areas of deep white matter ischaemia as well as microhaemorrhages, suggesting posterior reversible leucoencephalopathy syndrome. He unfortunately went into cardiac arrest and could not be revived. PMID- 28993346 TI - Abatacept in the treatment of adult dermatomyositis and polymyositis: a randomised, phase IIb treatment delayed-start trial. AB - OBJECTIVES: To study the effects of abatacept on disease activity and on muscle biopsy features of adult patients with dermatomyositis (DM) or polymyositis (PM). METHODS: Twenty patients with DM (n=9) or PM (n=11) with refractory disease were enrolled in a randomised treatment delayed-start trial to receive either immediate active treatment with intravenous abatacept or a 3 month delayed-start. The primary endpoint was number of responders, defined by the International Myositis Assessment and Clinical Studies Group definition of improvement (DOI), after 6 months of treatment. Secondary endpoints included number of responders in the early treatment arm compared with the delayed treatment arm at 3 months. Repeated muscle biopsies were investigated for cellular markers and cytokines. RESULTS: 8/19 patients included in the analyses achieved the DOI at 6 months. At 3 months of study, five (50%) patients were responders after active treatment but only one (11%) patient in the delayed treatment arm. Eight adverse events (AEs) were regarded as related to the drug, four mild and four moderate, and three serious AEs, none related to the drug. There was a significant increase in regulatory T cells (Tregs), whereas other markers were unchanged in repeated muscle biopsies. CONCLUSIONS: In this pilot study, treatment of patients with DM and PM with abatacept resulted in lower disease activity in nearly half of the patients. In patients with repeat muscle biopsies, an increased frequency of Foxp3+ Tregs suggests a positive effect of treatment in muscle tissue. PMID- 28993348 TI - Delayed spinal cord infarction following anterior cervical surgical decompression. AB - Anterior cervical discectomy and fusion (ACDF) for cord compression is a safe and effective procedure with good outcomes. However, worsening of myelopathy is the most feared adverse event of the surgery. We report the case of a 36-year-old male patient who presented with an acute non-traumatic C5-6 cervical disc herniation causing incomplete quadriparesis. He underwent an uncomplicated ACDF at C5-6, and after an initial period of improvement, he developed a delayed onset of an anterior cord syndrome on day 3, without any discerning cause. We have reviewed similar cases reported in the literature and believe that our patient's postsurgical course is consistent with a delayed ischaemic/reperfusion injury to the cord following surgical decompression and restoration of blood flow through the anterior spinal artery and we make suggestions for management of such clinical events. PMID- 28993349 TI - Aspirin safety in glucose-6-phosphate dehydrogenase deficiency patients with acute coronary syndrome undergoing percutaneous coronary intervention. AB - The use of aspirin, as part of a dual antiplatelet therapy regimen, is an established standard following coronary stenting in patients suffering from acute coronary syndrome (ACS). However, in glucose-6-phosphate dehydrogenase (G6PD) deficient patients, precaution is always taken with aspirin use, due to the risk of haemolysis. We reviewed all previous cases of G6PD deficient patients with ACS, in addition to a review of the available literature, to better understand the safety of aspirin use in this population. To date, there are no reported cases of haemolysis following aspirin use in this patient group and no guideline is established to date. PMID- 28993350 TI - Nodular fasciitis of soft tissue over the mandible. AB - Nodular fasciitis (NF) is an unusual, benign condition which can mimic more sinister, sarcomatous lesions both clinically and histologically. This case report presents a 35-year-old male, with a rapidly growing mass on the border of his left mandible, referred to a specialist head and neck unit. The initial presentation, radiology and cytology were initially inconclusive and the possibility of a malignant process was considered. Final histology was that of NF, the treatment of which is complete surgical excision. Therefore, NF is an important differential to consider when assessing similar clinical presentations, as highlighted in this case report. PMID- 28993351 TI - Haematuria in ADPKD: not always benign. Be aware! AB - Haematuria in patients with autosomal dominant polycystic kidney disease (ADPKD) is a very common manifestation. The cause of haematuria is often benign with the most common cause being haemorrhage within the renal cyst. But haematuria may also be caused by a coincident malignancy, the diagnosis of which may be missed if not investigated thoroughly. Herein, we present a case of ADPKD who presented to us with haematuria and was later found to have bladder cancer. PMID- 28993352 TI - Delays in diagnosis and treatment of extrapulmonary tuberculosis in Guatemala. AB - A 23-year-old indigenous Guatemalan man presented in 2016 to our clinic in Solola, Guatemala, with 10 months of recurrent neck swelling, fevers, night sweats and weight loss. Previously, he had sought care in three different medical settings, including a private physician-run clinic, a tertiary private cancer treatment centre and, finally, a rural government health post. With assistance from our institution's accompaniment staff, the patient was admitted to a public tertiary care hospital for work-up. Rifampin-susceptible tuberculosis was diagnosed, and appropriate treatment was begun. The case illustrates how low tuberculosis recognition among community health workers and health system segmentation creates obstacles to appropriate care, especially for patients with limited means. As a result, significant diagnostic and treatment delays can occur, increasing the public health burden of tuberculosis. PMID- 28993353 TI - Lipoedematous scalp: is there an association with fatty infiltration of the parotid? AB - Lipoedematous scalp (LS) is an extremely rare condition characterised by a soft and boggy consistency in the scalp due to an increased layer of subcutaneous tissue.In this report, we present a case of LS in a 64-year-old Indian woman. Clinical examination revealed only vague boggy lumpiness involving the whole of occipital scalp extending to parietal scalp. MRI scalp showed diffuse fatty infiltration of the scalp, particularly at the posterior parietal and occipital convexity extending to both lateral aspects of the cranium, with homogeneous signal in keeping with fat. Incidentally MRI also found diffuse fatty infiltration of the parotids.The aethiopathogenesis of LS is still unknown, however it is believed that the hormone leptin could be the key hormone in the dysregulation of fat deposition and distribution. This case report highlights the subtle features with which these cases can present and explores the literature on reported cases of LS. PMID- 28993354 TI - Endoscopic shaving of hair in a gastric bypass patient with a large bezoar. AB - Trichotillomania can be associated with the formation of trichobezoars (hair ball) usually located in the stomach. Trichobezoars may lead to complications including bowel obstruction, and perforation. Patients with a history of diabetes, certain psychiatric disorders, prior gastric surgery and poor mastication ability are at an increased risk of developing bezoars. We are presenting a case of patient who suffered from a large, recurrent trichobezoar, who had a history of gastric bypass surgery as well as trichotillophagia. The endoscopic method used to remove the large bezoar will also be discussed. We have reviewed the cases published, in which patients developed bezoars after undergoing gastric bypass surgery. The purpose of this study is to raise awareness among clinicians that patients with certain psychiatric issues who had prior gastric surgeries, are at eminent risk of bezoar formation. A multidisciplinary approach including cognitive behavioural therapy, dietary education and pharmacotherapy should be taken to prevent complications. PMID- 28993356 TI - Life-threatening parapharyngeal and retropharyngeal abscess in an infant. AB - Severe extensive deep neck abscess in an infant is uncommon. We share the case of a previously well 4-month old infant who was referred for a 4-day history of fever, lethargy and left lateral neck swelling. Contrast-enhanced CT scan revealed a large 5.3*8 cm collection involving the left parapharyngeal and retropharyngeal space, causing significant airway narrowing. 40 mL of frank pus was drained via intraoral incision and drainage with the aid of endoscope, and undesirable complications from an external approach were averted. The infant was extubated 48 hours postsurgery and was discharged home well after completion of 1 week of intravenous antibiotics. The child was discharged well from our follow-up at 1 month review. We discuss the pathophysiology of deep neck space abscesses, its incidence in the paediatric population and the various management options. PMID- 28993355 TI - Bilateral fungal keratitis with ring infiltrates: a rare scenario. AB - A 12-year-old boy presented to the emergency department with chief complaints of pain, redness, discharge and diminution of vision in both eyes over the previous 20 days. There was no history of preceding trauma, contact lens use, any eye drop usage or ocular surgery. Systemic history was not significant. Presenting uncorrected visual acuity in his right eye was counting fingers at 1 m and 20/200 in the left eye, with accurate projection of rays in both eyes. Slit lamp biomicroscopy showed the presence of bilateral diffuse conjunctival congestion, corneal ring infiltrates and epithelial defect with corneal oedema. Potassium hydroxide wet mount showed the presence of septate fungal hyphae. The patient was treated with topical 5% natamycin and 1% voriconazole over a period of 6 weeks. Best-corrected visual acuity was 20/600 in the right eye and 20/20 in the left eye at 6-month follow-up. PMID- 28993357 TI - RUNX1-RUNX1T1-positive acute myeloid leukaemia presenting as bilateral proptosis and multiple cranial nerve palsy. AB - We describe a unique presentation of acute myeloid leukaemia (AML) with myeloid sarcoma (MS), manifested as proptosis with multiple cranial nerve palsies in a 9 year-old boy. MRI of the brain revealed multiple enhancing lesions and bilateral mastoiditis, in addition to sagittal sinus thrombosis. Peripheral blood smear demonstrated blasts showing Auer rods. Bone marrow examination confirmed the diagnosis of AML. PCR was positive for RUNX1-RUNX1T1. Neurological deficits improved with induction chemotherapy for AML. Extramedullary MS can present simultaneously with or antedate AML. Common genetic aberrations include t(8;21) and inv(16). Therapy is akin to AML. An effect of MS on survival outcomes is variable. PMID- 28993358 TI - Novel management of a giant cervical myoma in a premenopausal patient. AB - Cervical myomas are rare and account for <1% of uterine leiomyomas. Clinical complications include bulk-related symptoms of pelvic pain, abnormal bleeding and infertility. While hysterectomies may be readily performed for postmenopausal women; the management of women with cervical myomas of childbearing age remains a challenge.Traditionally described fertility-preserving procedures such as myomectomy, endometrial ablation or myolysis may only be applied to leiomyomas within the uterine corpus. Little is known about the surgical management of its cervical counterpart.Radical abdominal trachelectomy has been described as a potential fertility-preserving procedure in the management of women with early cervical cancer. As such, we present a case of a giant cervical myoma that was treated with an abdominal trachelectomy in an attempt to preserve fertility. PMID- 28993359 TI - Hoarseness as a presentation of mycosis fungoides infiltrating the larynx. AB - Laryngeal involvement is a rare manifestation of mycosis fungoides (MF), with only nine reported cases of cutaneous T cell lymphoma with laryngeal or vocal cord involvement. Herein, we report the case of a patient with a 7-year history of MF who presented to the emergency department with hoarseness, throat tightness and cough, as well as erythroderma and skin tumours. Laryngoscopy and CT imaging were concerning for lymphomatous involvement of the left false vocal cord. A biopsy was taken of the false vocal cord lesion, which revealed an aberrant immunophenotype consistent with MF. The patient was started on doxorubicin with initial rapid improvement in symptoms. Within 2 months, her respiratory status and skin involvement worsened. Subsequent studies showed bone marrow involvement. The patient expired 4 months after original presentation. This report describes the patient's presentation and clinical course, and reviews the literature on vocal cord and laryngeal involvement of MF. PMID- 28993360 TI - Pertussis manifesting as recurrent cough and wheezing in an incompletely vaccinated 8-month-old infant. AB - Pertussis is an acute respiratory illness caused by Bordetella pertussis, showing a re-emergence in developed countries. However, it is probably under-recognised and, as a consequence, its burden is underestimated. Here, we report the clinical case of an infant diagnosed with pertussis, despite a regular schedule of vaccination, thanks to a careful clinical evaluation, including personal and family history. In addition to pointing the attention on a precocious diagnosis of atypical cases of pertussis, this case report further raised the issue of modifying and/or implementing the immunisation strategy, considering the ongoing changes of social (eg, immigration) and sanitary (eg, vaccine coverage) background in Italy and all over the Europe. PMID- 28993361 TI - A rare case of extra-adrenal bilateral perirenal and periureteric myelolipoma. AB - A 30-year-old immunocompetent female presented with right flank pain since 3 years. MRI revealed a large well-defined T1 and T2 hypointense mildly enhancing lesion in the right anterior pararenal space displacing the right kidney and encasing the right ureter with T2 hyperintense wall thickening of the left renal pelvis and ureter. A provisional diagnosis of solitary fibrous tumour was kept. Bilateral double J stenting was done for hydronephrosis. Surgical debulking of the lesion was done with biopsy from the left periureteral wall thickening and was found to be myelolipoma on histopathological examination. This case is a novel variety of myelolipoma which is lipid poor, extra-adrenal and in bilateral perirenal and periureteric location. PMID- 28993362 TI - Unusual case of urethral steinstrasse following laser cystolitholapaxy. AB - Urethral steinstrasse is a rare finding. This case describes a 35-year-old man presenting with urethral steinstrasse 4 weeks following laser cystolitholapaxy of a large bladder stone. PMID- 28993363 TI - Rare postoperative complication: Clostridium perfringens septic shock following elective abdominal surgery. AB - Postoperative infections are one of the most common complications in general surgery, and while rates have reduced with the routine administration of perioperative antibiotics, around 5% of patients undergoing a surgical procedure will develop an infective complication.1 The Gram-positive, obligate anaerobe, Clostridium perfringens, is a well-known pathogen that forms part of both the environmental and gastrointestinal flora.2 While more commonly associated with food poisoning, anaerobic cellulitis and traumatic gas gangrene, rare cases of spontaneous non-traumatic gas gangrene of abdominal viscera have also been recorded.3 Although potentially treatable with appropriate antibiotic cover, cases of C. perfringens can rapidly progress into fulminant and fatal sepsis.4 Moreover, the timing of symptom onset postoperatively can vary significantly, reports ranging from hours to days.5 6 We report a case of C. perfringens-induced septic shock following elective bowel resection. PMID- 28993364 TI - Durable complete remission with combination chemotherapy and bortezomib in HIV associated plasmablastic lymphoma. AB - Plasmablastic lymphoma (PBL) is an aggressive form of non-Hodgkin's lymphoma (NHL) classically seen in patients infected with the human immunodeficiency virus, but can also be seen in other immunocompromised states such as transplant recipients, autoimmune diseases and the elderly. PBL is generally associated with a poor prognosis despite chemotherapy. There is evidence supporting the use of bortezomib in combination with standard chemotherapy to achieve durable responses in patients with PBL. We describe a patient with acquired immunodeficiency syndrome who presented with rectal pain and bright red blood per rectum. He was diagnosed with stage IVA PBL with anorectal, nodal, calvarial and hepatic involvement. Along with highly active antiretroviral therapy, he was treated with six cycles of dose adjusted etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (DA-EPOCH) plus bortezomib resulting in durable complete remission 30 months after diagnosis. PMID- 28993365 TI - Videoscopic-assisted removal of a left ventricular mass in an octogenarian. PMID- 28993366 TI - Mitral valve prosthesis implanted in the atrial position in a patient with extensive calcification extending from epicardium to mitral annulus. PMID- 28993367 TI - Isolated adductor myocysticercosis in a 6-year-old girl. PMID- 28993368 TI - Complete Kawasaki disease (KD) with peculiar skin manifestations. PMID- 28993370 TI - Who Would Be Branded With Failure? PMID- 28993369 TI - Spontaneous bilateral carpopedal spasm in a bulimic patient. PMID- 28993371 TI - "Pumping Iron" to Improve Exercise Performance in Heart Failure: New Data and New Guidelines. PMID- 28993372 TI - Spatial Gene Profiling in the Ischemic Heart: Fibroblasts Put on Their SOX. PMID- 28993373 TI - Wine and Cardiovascular Health: A Comprehensive Review. AB - Alcoholic beverages have been consumed for thousands of years, attracting great human interest for social, personal, and religious occasions. In addition, they have long been debated to confer cardioprotective benefits. The French Paradox is an observation of a low prevalence of ischemic heart disease, with high intakes of saturated fat, a phenomenon accredited to the consumption of red wine. Although many epidemiological investigations have supported this view, others have attributed it to beer or spirits, with many suggesting that the drink type is not important. Although excessive consumption of alcoholic beverages is commonly regarded to be detrimental to cardiovascular health, there is a debate as to whether light-to-moderate intake is cardioprotective. Although there is extensive epidemiological support for this drinking pattern, a consensus has not been reached. On the basis of published work, we describe the composition of wine and the effects of constituent polyphenols on chronic cardiovascular diseases. PMID- 28993374 TI - Scientists Correct a Pathogenic Gene Mutation in Human Embryos. PMID- 28993375 TI - Sedentary Behavior and Subclinical Cardiac Injury: Results From the Dallas Heart Study. PMID- 28993376 TI - Letter by Vos et al Regarding Article, "Primary Prevention With Statin Therapy in the Elderly: New Meta-Analyses From the Contemporary JUPITER and HOPE-3 Randomized Trials". PMID- 28993377 TI - Letter by Kleipool et al Regarding Article, "Primary Prevention With Statin Therapy in the Elderly: New Meta-Analyses From the Contemporary JUPITER and HOPE 3 Randomized Trials". PMID- 28993378 TI - Characterisation of the rural indigent population in Burkina Faso: a screening tool for setting priority healthcare services in sub-Saharan Africa. AB - BACKGROUND: In Africa, health research on indigent people has focused on how to target them for services, but little research has been conducted to identify the social groups that compose indigence. Our aim was to identify what makes someone indigent beyond being recognised by the community as needing a card for free healthcare. METHODS: We used data from a survey conducted to evaluate a state-led intervention for performance-based financing of health services in two districts of Burkina Faso. In 2015, we analysed data of 1783 non-indigents and 829 people defined as indigents by their community in 21 villages following community-based targeting processes. Using a classification tree, we built a model to select socioeconomic and health characteristics that were likely to distinguish between non-indigents and indigents. We described the screening performance of the tree using data from specific nodes. RESULTS: Widow(er)s under 45 years of age, unmarried people aged 45 years and over, and married women aged 60 years and over were more likely to be identified as indigents by their community. Simple rules based on age, marital status and gender detected indigents with sensitivity of 75.6% and specificity of 55% among those 45 years and over; among those under 45, sensitivity was 85.5% and specificity 92.2%. For both tests combined, sensitivity was 78% and specificity 81%. CONCLUSION: In moving towards universal health coverage, Burkina Faso should extend free access to priority healthcare services to widow(er)s under 45, unmarried people aged 45 years and over, and married women aged 60 years and over, and services should be adapted to their health needs. ETHICS CONSIDERATIONS: The collection, storage and release of data for research purposes were authorised by a government ethics committee in Burkina Faso (Decision No. 2013-7-066). Respondent consent was obtained verbally. PMID- 28993379 TI - Knowledge, attitudes, perceptions and habits towards antibiotics dispensed without medical prescription: a qualitative study of Spanish pharmacists. AB - OBJECTIVE: To investigate community pharmacists' knowledge, attitudes, perceptions and habits with regard to antibiotic dispensing without medical prescription in Spain. METHODS: A qualitative research using focus group method (FG) in Galicia (north-west Spain). FG sessions were conducted in the presence of a moderator. A topic script was developed to lead the discussions, which were audiorecorded to facilitate data interpretation and transcription. Proceedings were transcribed by an independent researcher and interpreted by two researchers working independently. We used the Grounded Theory approach. SETTING: Community pharmacies in Galicia, region Norwest of Spain. PARTICIPANTS: Thirty pharmacists agreed to participate in the study, and a total of five FG sessions were conducted with 2-11 pharmacists. We sought to ensure a high degree of heterogeneity in the composition of the groups to improve our study's external validity. Pharmacists' participation had no gender or age restrictions, and an effort was made to form FGs with pharmacists who were both owners and non-owners, provided in all cases that they were Official Colleges of Pharmacists-registered community pharmacists. For the purpose of conducting FG discussions, the basic methodological principle of allowing groups to attain their 'own structural identity' was applied. MAIN OUTCOME MEASUREMENTS: Community pharmacists' habits and knowledge with regard to antibiotics and identification of the attitudes and/or factors that influence antibiotic dispensing without medical prescription. RESULTS: Pharmacists attributed the problem of antibiotics dispensed without medical prescription and its relationship to antibiotic resistance to the following attitudes: external responsibility (doctors, dentists and the National Health Service (NHS)); acquiescence; indifference and lack of continuing education. CONCLUSIONS: Despite being a problem, antibiotic dispensing without a medical prescription is still a common practice in community pharmacies in Galicia, Spain. This practice is attributed to acquiescence, indifference and lack of continuing education. The problem of resistance was ascribed to external responsibility, including that of patients, physicians, dentists and the NHS. PMID- 28993380 TI - Factors related to the development of health-promoting community activities in Spanish primary healthcare: two case-control studies. AB - OBJECTIVE: Spanish primary healthcare teams have the responsibility of performing health-promoting community activities (CAs), although such activities are not widespread. Our aim was to identify the factors related to participation in those activities. DESIGN: Two case-control studies. SETTING: Performed in primary care of five Spanish regions. SUBJECTS: In the first study, cases were teams that performed health-promoting CAs and controls were those that did not. In the second study (on case teams from the first study), cases were professionals who developed these activities and controls were those who did not. MAIN OUTCOME MEASURES: Team, professional and community characteristics collected through questionnaires (team managers/professionals) and from secondary sources. RESULTS: The first study examined 203 teams (103 cases, 100 controls). Adjusted factors associated with performing CAs were percentage of nurses (OR 1.07, 95% CI 1.01 to 1.14), community socioeconomic status (higher vs lower OR 2.16, 95% CI 1.18 to 3.95) and performing undergraduate training (OR 0.44, 95% CI 0.21 to 0.93). In the second study, 597 professionals responded (254 cases, 343 controls). Adjusted factors were professional classification (physicians do fewer activities than nurses and social workers do more), training in CAs (OR 1.9, 95% CI 1.2 to 3.1), team support (OR 2.9, 95% CI 1.5 to 5.7), seniority (OR 1.06, 95% CI 1.03 to 1.09), nursing tutor (OR 2.0, 95% CI 1.1 to 3.5), motivation (OR 3.7, 95% CI 1.8 to 7.5), collaboration with non-governmental organisations (OR 1.9, 95% CI 1.2 to 3.1) and participation in neighbourhood activities (OR 3.1, 95% CI 1.9 to 5.1). CONCLUSIONS: Professional personal characteristics, such as social sensitivity, profession, to feel team support or motivation, have influence in performing health-promoting CAs. In contrast to the opinion expressed by many professionals, workload is not related to performance of health-promoting CAs. PMID- 28993381 TI - Prevalence of and factors associated with fewer than 20 remaining teeth in Taiwanese adults with disabilities: a community-based cross-sectional study. AB - OBJECTIVES: To examine the prevalence of and the factors associated with a number of remaining teeth (NRT) <20 among adults with disabilities. DESIGN: A community based, cross-sectional descriptive study. SETTING: This study was part of a health promotion programme designed for community-dwelling adults with disabilities. PARTICIPANTS: A total of 549 adults with disabilities, aged 20-80 years, living in the community in Chiayi County in Taiwan. OUTCOME MEASURES: Various parameters, including NRT, oral health behaviours (ie, oral hygiene, dietary habits and substance use), comorbidities, disability classification and capability for performing activities of daily living, were measured. Data were statistically analysed using descriptive statistics and multivariate logistic regression analysis. RESULTS: The mean NRT was 18.1 (SD=10.9); 44.8% of participants had NRT <20 (including 13.7% edentulous participants). Most participants had poor oral hygiene: 83.4% reported seldom using dental floss, 78% did not undergo regular 6-monthly dental check-ups and 77.4% seldom brushed their teeth after meal. After adjusting for potentially confounding variables, the intellectual disability group had a significantly higher risk of an NRT <20 than the physical disability group (OR 2.30, 95% CI 1.30 to 4.08). Additionally, the rare use of dental floss and hypertension significantly increased the possibility of an NRT <20 (OR 1.73-2.12, 95% CI 1.15 to 3.71). CONCLUSIONS: An NRT <20 and edentulism were highly prevalent among adults with disabilities, who displayed poor oral hygiene behaviours. Adults with intellectual disabilities had a greater likelihood of having an NRT <20 than did those with physical disability. In addition to unmodifiable factors, the poor use of dental floss was significantly associated with an NRT <20. PMID- 28993382 TI - Comparison of two methods to estimate adverse events in the IBEAS Study (Ibero American study of adverse events): cross-sectional versus retrospective cohort design. AB - BACKGROUND: Adverse events (AEs) epidemiology is the first step to improve practice in the healthcare system. Usually, the preferred method used to estimate the magnitude of the problem is the retrospective cohort study design, with retrospective reviews of the medical records. However this data collection involves a sophisticated sampling plan, and a process of intensive review of sometimes very heavy and complex medical records. Cross-sectional survey is also a valid and feasible methodology to study AEs. OBJECTIVES: The aim of this study is to compare AEs detection using two different methodologies: cross-sectional versus retrospective cohort design. SETTING: Secondary and tertiary hospitals in five countries: Argentina, Colombia, Costa Rica, Mexico and Peru. PARTICIPANTS: The IBEAS Study is a cross-sectional survey with a sample size of 11 379 patients. The retrospective cohort study was obtained from a 10% random sample proportional to hospital size from the entire IBEAS Study population. METHODS: This study compares the 1-day prevalence of the AEs obtained in the IBEAS Study with the incidence obtained through the retrospective cohort study. RESULTS: The prevalence of patients with AEs was 10.47% (95% CI 9.90 to 11.03) (1191/11 379), while the cumulative incidence of the retrospective cohort study was 19.76% (95% CI 17.35% to 22.17%) (215/1088). In both studies the highest risk of suffering AEs was seen in Intensive Care Unit (ICU) patients. Comorbid patients and patients with medical devices showed higher risk. CONCLUSION: The retrospective cohort design, although requires more resources, allows to detect more AEs than the cross-sectional design. PMID- 28993383 TI - Impacts of undetected and inadequately treated hypertension on incident stroke in China. AB - OBJECTIVES: China carries the greatest burden of stroke given its largest volume of people with hypertension. This study assessed the impacts of suboptimal controls of hypertension on incident stroke and projected the number of patients with stroke saved after the control of blood pressure improved in population. SETTING: Anhui, China. PARTICIPANTS: We examined data from the Anhui cohort of 2001-2011, consisting of 3336 participants aged >=60 years who were randomly recruited from the urban and rural Anhui. 2852 participants (89.2%) had hypertensive status measured and no stroke at baseline, and were followed up until 2011 in three surveys using a standard method of interview. RESULTS: At baseline, 1646 participants (57.7%) were identified to have hypertension, among whom 912 (55.4%) were previously undetected, 115 (7.0%) detected but not treated, 452 (27.5%) treated but not controlled and only 127 (7.7%) controlled. During the 10-year follow-up, 211 incident stroke cases (12.8/1000 person-years) occurred. Compared with normotensive individuals at baseline, multivariate adjusted HR for having stroke increased in those with undetected hypertension by 1.63 (95%CI 1.15 to 2.32), untreated by 2.21 (1.26-3.85) and uncontrolled hypertension by 3.34 (2.28-4.88), but did not differ from those with controlled hypertension (1.34; 0.60-2.99). Based on a two-fold increase in the detection and management of current levels of hypertension and algorithms on the current situation in China, approximately 250 000 incident stroke cases could be prevented annually. CONCLUSIONS: In China, hypertension is frequently undetected or inadequately treated. With appropriate management of hypertension, a substantial number of people could be saved form stroke. PMID- 28993384 TI - Can coenzyme Q10 supplementation effectively reduce human tumour necrosis factor alpha and interleukin-6 levels in chronic diseases? Protocol for a systematic review and meta-analysis of randomised controlled trials. AB - INTRODUCTION: Inflammation, as a critical factor, can cause numerous chronic diseases by creating various proinflammatory cytokines. Coenzyme Q10 (CoQ10) can potentially exert an anti-inflammatory agent; in turn, this agent can reduce the systemic inflammatory response. The aims of this study are to conduct a comprehensive systematic review and a meta-analysis for the determination of the CoQ10 efficacy on the changes in serum interleukin-6 (IL-6) and the tumour necrosis factor-alpha (TNF-alpha) levels in unhealthy subjects. METHOD AND ANALYSIS: We will conduct an electronic search for articles published between January 1990 and January 2017 using a prespecified search strategy in MEDLINE, SCOPUS, EMBASE, CENTRAL and Web of Science.Our search will focus only on randomised controlled clinical trials in unhealthy subjects that employ either a parallel or a crossover design; this search will involve concurrent control groups. The primary outcomes of the literature are to determine the CoQ10 efficacy on the changes in the serum IL-6 and the TNF-alpha levels in unhealthy subjects. Secondary outcomes such as body mass index, serum adiponectin and high sensitivity C-reactive protein levels, lipid profile and the heterogeneity assessment of the primary studies will be evaluated. The stages of screen articles, the extracts of relevant data and the assessment of study quality using the Cochrane risk of bias tool will be conducted independently by the two reviewers. Any disagreement will be resolved by discussion with a third person. If the number of eligible studies is sufficient, we will carry out a meta analysis according to both outcomes. ETHICS AND DISSEMINATION: This study is the protocol for a systematic review and no ethics approval is needed. The findings from the full systematic review will be published in a peer-reviewed journal, and they will also be exhibited at national/international academic and clinical conferences. TRIAL REGISTRATION NUMBER: CRD42016052200. PMID- 28993385 TI - Prevalence of Trichomonas vaginalis infection and protozoan load in South African women: a cross-sectional study. AB - OBJECTIVES: Trichomonas vaginalis is thought to be the most common non-viral sexually transmitted infection worldwide. We investigated the prevalence, risk factors and protozoan load of T. vaginalis infection in South African women. METHODS: A cross-sectional study of 604 women was conducted at 25 primary healthcare facilities in rural South Africa (Mopani district). T. vaginalis DNA was detected in vaginal and rectal swabs. In univariate and multivariate analyses, the T. vaginalis infection was investigated in relation to demographic characteristics, medical history and behavioural factors. The T. vaginalis load was determined as the logarithm of DNA copies per microlitre sample solution. RESULTS: Collected vaginal and rectal swabs were tested for T. vaginalis DNA. Prevalence of vaginal T. vaginalis was 20% (95% CI 17.0% to 23.4%) and rectal 1.2% (95% CI 0.6% to 2.4%). Most women (66%) with a vaginal infection were asymptomatic. Factors associated with T. vaginalis infection were a relationship status of single (OR 2.4; 95% CI 1.5 to 4.0; p<0.001) and HIV positive infection (OR 1.6; 95% CI 1.0 to 2.6; p=0.041). Women with vaginal T. vaginalis infection were more likely to have concurrent Chlamydia trachomatis rectal infection than those without vaginal infection (12%vs3%; p<0.001; OR 4.1). A higher median T. vaginalis load was observed among women with observed vaginal discharge compared with those without vaginal discharge (p=0.025). CONCLUSIONS: Vaginal trichomoniasis is highly prevalent in rural South Africa, especially among single women and those with HIV infection, and often presents without symptoms. PMID- 28993386 TI - Patterns and correlates of active commuting in adults with type 2 diabetes: cross sectional evidence from UK Biobank. AB - OBJECTIVES: To describe the active commuting (AC) patterns of adults with type 2 diabetes and how these relate to physical activity and sedentary behaviour in UK Biobank. Social and environmental correlates of AC will also be explored. DESIGN: Cross-sectional analysis of a cohort study. SETTINGS: This is a population cohort of over 500 000 people recruited from 22 centres across the UK. Participants aged between 37 and 73 years were recruited between 2006 and 2010. PARTICIPANTS: 6896 participants with a self-reported type 2 diabetes diagnosis who reported commuting to work and had complete covariate data were included in the analysis. EXPOSURE MEASURES: Exposure measures were AC to work, measured as usual mode of transport. OUTCOME MEASURES: Outcome measures were weekly minutes of moderate to vigorous physical activity (MVPA), hours/day of sedentary time and participation in active travel. RESULTS: AC (reporting walking or cycling to work only) was reported by 5.5% of participants, with the great majority using the car to commute (80%). AC was associated with an additional 73 (95% CI 10.8 to 134.9) and 105 (95% CI 41.7 to 167.2) weekly minutes of MVPA for men and women, respectively. AC was associated with reduced sedentary time (beta -1.1, 95% CI 1.6 to -0.7 hours/day for men; and beta -0.8, 95% CI -1.2 to -0.3 hours/day for women). Deprivation and distance from home to work were identified as correlates of AC behaviour. CONCLUSIONS: Rates of AC are very low in adults with type 2 diabetes. However, AC offers a potentially sustainable solution to increasing physical activity and reducing sedentary behaviour. Therefore, strategies to improve the environment and encourage AC may help to increase population levels of physical activity and reduce the disease burden associated with type 2 diabetes. PMID- 28993387 TI - Risk and adverse outcomes of fractures in patients with liver cirrhosis: two nationwide retrospective cohort studies. AB - OBJECTIVE: The aim of this study is to evaluate fracture risk and post-fracture outcomes in patients with and without liver cirrhosis (LC). DESIGN: Retrospective cohort study and nested fracture cohort study. SETTING: This study was based on Taiwan's National Health Insurance Research Database that included information on: (1) 3941 patients aged 20 years and older newly diagnosed with LC between 2000 and 2003; (2) 688290 hospitalised fracture patients aged 20 years and older between 2006 and 2013. PRIMARY AND SECONDARY OUTCOME MEASURES: Followed-up events of fracture from 2000 to 2008 were noted from medical claims to evaluate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of fracture associated with LC. Adjusted odds ratios (ORs) and 95% CIs of adverse events after fracture were compared among patients with and without LC RESULTS: The incidences of fracture for people with and without LC were 29.1 and 17.2 per 1000 person-years, respectively. Compared with controls, the adjusted HR of fracture was 1.83 (95% CI 1.67 to 2.01) for patients with LC. Previous LC was associated with risks of septicaemia (OR 1.77, 95% CI 1.60 to 1.96), acute renal failure (OR 1.63, 95% CI 1.33 to 1.99), and 30-day in-hospital mortality (OR 1.61, 95 %CI 1.37 to 1.89) after fracture. CONCLUSION: LC was associated with higher risk of fracture; patients with LC in particular had more complications and 30-day in-hospital mortality after fracture. Fracture prevention and attention to post-fracture adverse events are needed for these susceptible populations. PMID- 28993388 TI - MEDication reminder APPs to improve medication adherence in Coronary Heart Disease (MedApp-CHD) Study: a randomised controlled trial protocol. AB - INTRODUCTION: The growing number of smartphone health applications available in the app stores makes these apps a promising tool to help reduce the global problem of non-adherence to long-term medications. However, to date, there is limited evidence that available medication reminder apps are effective. This study aims to determine the impact of medication reminder apps on adherence to cardiovascular medication when compared with usual care for people with coronary heart disease (CHD) and to determine whether an advanced app compared with a basic app is associated with higher adherence. METHODS AND ANALYSIS: Randomised controlled trial with follow-up at 3 months to evaluate the feasibility and effectiveness of medication reminder apps on medication adherence compared with usual care. An estimated sample size of 156 patients with CHD will be randomised to one of three groups (usual care group, basic medication reminder app group and advanced medication reminder app group). The usual care group will receive standard care for CHD with no access to a medication reminder app. The basic medication reminder app group will have access to a medication reminder app with a basic feature of providing simple daily reminders with no interactivity. The advanced medication reminder app group will have access to a medication reminder app with additional interactive and customisable features. The primary outcome is medication adherence measured by the eight-item Morisky Medication Adherence Scale at 3 months. Secondary outcomes include clinical measurements of blood pressure and cholesterol levels, and medication knowledge. A process evaluation will also be performed to assess the feasibility of the intervention by evaluating the acceptability, utility and engagement with the apps. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Western Sydney Local Health Network Human Research Ethics Committee (AU/RED/HREC/1/WMEAD/3). Study findings will be disseminated via usual scientific forums. TRIAL REGISTRATION NUMBER: ACTRN12616000661471; Pre-results. PMID- 28993390 TI - Thermal clothing to reduce heart failure morbidity during winter: a randomised controlled trial. AB - OBJECTIVE: To examine whether providing thermal clothing improved the health of patients with heart failure during winter. DESIGN: Parallel group randomised controlled trial. SETTING: Large public hospital in Brisbane during winter 2016. PARTICIPANTS: 91 patients with systolic or diastolic heart failure who were over 50 years old. INTERVENTION: 47 patients were randomised to receive thermal clothes (socks, top and hat) and 44 received usual care. Patients could not be blinded to their randomised group. All patients' data were available for the primary outcome which was collected blind to randomised group. MAIN OUTCOME MEASURES: The primary outcome was the mean number of days in hospital during winter. Secondary outcomes included quality of life and sleep, and blood tests were collected for cardiovascular risk factors. Participants completed clothing diaries in midwinter which were used to estimate their overall clothing insulation using the 'clo'. Monitors inside the participants' homes recorded indoor temperatures throughout winter. RESULTS: The mean number of days in hospital during winter was 4.2 in the usual care group and 3.0 in the thermal clothing group (mean difference -1.2 days, 95% CI -4.8 to 2.5 days). Most participants (85%) in the thermal clothing group reported using the thermals. There was an increase in overall clothing insulation at night in the thermal clothing group (mean difference 0.13 clo, 95% CI 0.03 to 0.23). Most participants in both groups did not wear sufficient clothing (defined as a clo below 1) and regularly experienced indoor temperatures below 18 degrees C during midwinter. CONCLUSIONS: There was no clear statistical improvement in health in the thermal clothing group. Efforts to improve health during winter may need to focus on passive interventions such as home insulation rather than interventions that target behaviour change. TRIAL REGISTRATION NUMBER: ACTRN12615001023549; Results. PMID- 28993389 TI - Innovative Telemonitoring Enhanced Care Programme for Chronic Heart Failure (ITEC CHF) to improve guideline compliance and collaborative care: protocol of a multicentre randomised controlled trial. AB - INTRODUCTION: Chronic heart failure (CHF) is a life-threatening chronic disease characterised by periodic exacerbations and recurrent hospitalisations. In the management of CHF, patient compliance with evidence-based clinical guidelines is essential, but remains difficult practically. The objective of this study is to examine whether an Innovative Telemonitoring Enhanced Care Programme for CHF (ITEC-CHF) improves patients' compliance, and associated health and economic outcomes. METHODS AND ANALYSIS: An open multicentre randomised controlled trial has been designed. Patients will be recruited and randomised to receive either ITEC-CHF (n=150) or usual care CHF (n=150) for at least 6 months. ITEC-CHF combines usual care and an additional telemonitoring service including remote weight monitoring, structured telephone support and nurse-led collaborative care. The primary outcomes are the compliance rates with the best-practice guidelines for daily weight monitoring. The secondary outcomes include the compliance with other guideline recommendations (health maintenance, medication, diet and exercise), health (health-related quality of life, risk factors, functional capacity and psychological states) and economic outcomes related to the use of healthcare resources such as hospital readmissions and general practitioner/emergency department visits. ETHICS AND DISSEMINATION: The clinical trial has been approved by Peninsula Health Human Research Ethics Committee (HREC Reference: HREC/14/PH/27), Royal Perth Hospital Human Research Ethics Committee (Reference: 15-081) and the Curtin University Human Research Ethics Committee (Reference: HR 181/2014). We will disseminate the final results to the public via conferences and journal publications. A final study report will also be provided to the ethics committees. TRIAL REGISTRATION NUMBER: Registered with Australian New Zealand Clinical Trial Registry (ACTRN12614000916640). PMID- 28993391 TI - Evaluating a novel Integrated Community of Care (ICoC) for patients from an urbanised low-income community in Singapore using the participatory action research (PAR) methodology: a study protocol. AB - INTRODUCTION: Poorer health outcomes and disproportionate healthcare use in socioeconomically disadvantaged patients is well established. However, there is sparse literature on effective integrated care interventions that specifically target these high-risk individuals. The Integrated Community of Care (ICoC) is a novel care model that integrates hospital-based transitional care with health and social care in the community for high-risk individuals living in socially deprived communities. This study aims to evaluate the effectiveness of the ICoC in reducing acute hospital use and investigate the implementation process and its effects on clinical outcomes using a mixed-methods participatory action research (PAR) approach. METHODS AND ANALYSIS: This is a single-centre prospective, controlled, observational study performed in the SingHealth Regional Health System. A total of 250 eligible patients from an urbanised low-income community in Singapore will be enrolled during their index hospitalisation. Our PAR model combines two research components: quantitative and qualitative, at different phases of the intervention. Outcomes of acute hospital use and health-related quality of life are compared with controls, at 30 days and 1 year. The qualitative study aims at developing a more context-specific social ecological model of health behaviour. This model will identify how influences within one's social environment: individual, interpersonal, organisational, community and policy factors affect people's experiences and behaviours during care transitions from hospital to home. Knowledge on the operational aspects of ICoC will enrich our evidence-based strategies to understand the impact of the ICoC. The blending of qualitative and quantitative mixed methods recognises the dynamic implementation processes as well as the complex and evolving needs of community stakeholders in shaping outcomes. ETHICS AND DISSEMINATION: Ethics approval was granted by the SingHealth Centralised Institutional Review Board (CIRB 2015/2277). The findings from this study will be disseminated by publications in peer-reviewed journals, scientific meetings and presentations to government policy-makers. TRIAL REGISTRATION NUMBER: NCT02678273. PMID- 28993392 TI - Implementation outcome assessment instruments used in physical healthcare settings and their measurement properties: a systematic review protocol. AB - INTRODUCTION: Over the past 10 years, research into methods that promote the uptake, implementation and sustainability of evidence-based interventions has gathered pace. However, implementation outcomes are defined in different ways and assessed by different measures; the extent to which these measures are valid and reliable is unknown. The aim of this systematic review is to identify and appraise studies that assess the measurement properties of quantitative implementation outcome instruments used in physical healthcare settings, to advance the use of precise and accurate measures. METHODS AND ANALYSIS: The following databases will be searched from inception to March 2017: MEDLINE, EMBASE, PsycINFO, CINAHL and the Cochrane Library. Grey literature will be sought via HMIC, OpenGrey, ProQuest for theses and Web of Science Conference Proceedings Citation Index-Science. Reference lists of included studies and relevant reviews will be hand searched. Three search strings will be combined to identify eligible studies: (1) implementation literature, (2) implementation outcomes and (3) measurement properties. Screening of titles, abstracts and full papers will be assessed for eligibility by two reviewers independently and any discrepancies resolved via consensus with the wider team. The methodological quality of the studies will be assessed using the COnsensus-based Standards for the selection of health Measurement INstruments checklist. A set of bespoke criteria to determine the quality of the instruments will be used, and the relationship between instrument usability and quality will be explored. ETHICS AND DISSEMINATION: Ethical approval is not necessary for systematic review protocols. Researchers and healthcare professionals can use the findings of this systematic review to guide the selection of implementation outcomes instruments, based on their psychometric quality, to assess the impact of their implementation efforts. The findings will also provide a useful guide for reviewers of papers and grants to determine the psychometric quality of the measures used in implementation research. TRIAL REGISTRATION NUMBER: International Prospective Register of Systematic Reviews (PROSPERO): CRD42017065348. PMID- 28993393 TI - Recurrent wheeze and its relationship with lung function and airway inflammation in preschool children: a cross-sectional study in South Korea. AB - BACKGROUND: Relationship between recurrent wheeze and airway function and inflammation in preschool children is not fully known. OBJECTIVE: To investigate the relationship between recurrent wheeze and airway inflammation, lung function, airway hyper-reactivity (AHR) and atopy in preschool children. DESIGN: Observational study, comparing forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and mid-forced expiratory flow (FEF25%-75%), dose-response slope (DRS), exhaled nitric oxide (eNO) and atopic sensitisation between children with recurrent wheeze and those without. SETTING: Population-based, cross sectional study in Seoul and the Gyeonggi province of Korea conducted as a government-funded programme to perform standardised measurement of the prevalence of allergic diseases, and related factors, in preschool children. PARTICIPANTS: 900 children aged 4-6 years. PRIMARY AND SECONDARY OUTCOME MEASURES: eNO, FEV1/FVC, FEF25%-75%, DRS, atopic sensitisation and allergic diseases. METHODS: Children completed the modified International Study of Asthma and Allergies in Childhood questionnaire and underwent eNO assessments, spirometry, methacholine bronchial provocation tests and skin prick tests. Recurrent wheeze was defined as having a lifetime wheeze of more than three episodes, based on the questionnaire. The frequency of hospitalisation and emergency room visits was also obtained by means of the questionnaire. 'Current' wheeze was defined as having symptoms or treatments within the past 12 months. RESULTS: The prevalence of recurrent wheeze was 13.4%. Children with recurrent wheeze showed a higher prevalence of lifetime or current allergic rhinitis (p=0.01 and p=0.002, respectively) and lifetime atopic dermatitis (p=0.007). Children with recurrent wheeze showed lower FEV1/FVC (p=0.033) and FEF25%-75% (p=0.004), and higher eNO levels (p=0.013) than those without recurrent wheeze. However, the DRS, prevalence of atopic sensitisation and serum IgE levels were not significantly different between the two groups. CONCLUSIONS: Recurrent wheeze in preschool children may be associated with airway inflammation and diminished airway function, but not with AHR or atopy. PMID- 28993394 TI - Recruitment, adherence, and retention of endometrial cancer survivors in a behavioural lifestyle programme: the Diet and Exercise in Uterine Cancer Survivors (DEUS) parallel randomised pilot trial. AB - OBJECTIVE: Healthy eating and physical activity may help endometrial cancer survivors (ECS) improve their quality of life. However, most ECS do not meet the relevant guidelines. This pilot trial aimed to test the study feasibility procedures for a definitive trial of a behavioural lifestyle programme. DESIGN AND SETTING: This 24-week parallel two-arm randomised pilot trial took place in two hospitals in London, UK (April 2015-June 2016). PARTICIPANTS: Sixty disease free ECS within 3 years of diagnosis. INTERVENTIONS: Participants were randomised using minimisation to receive the intervention or care as usual. The 'Shape-Up following cancer treatment' programme used self-monitoring, goal-setting, self incentives, problem-solving and group social support for 12 hours over 8 weeks to help survivors improve their eating and physical activity. OUTCOME MEASURES: The main outcome measures were recruitment, adherence, and retention rates. Further outcomes included barriers to participation and feedback on programme satisfaction. RESULTS: Of the 296 potentially eligible ECS, 20% (n=60) were randomly allocated to the active intervention (n=29) or control group (n=31). Three participants in each arm were deemed ineligible after randomisation and excluded from analysis. Twenty participants (77%; 95% CI 61% to 93%) adhered to the intervention and provided generally favourable feedback. At 24 weeks, 25/26 (96%; 95% CI 89% to 100%) intervention and 24/28 (86%; 95% CI 73% to 99%) control participants completed their assessment. No intervention-related adverse events were reported. Among eligible survivors who declined study participation (n=83), inconvenience (78%; 95% CI 69% to 87%) was the most common barrier. CONCLUSIONS: The trial was feasible to deliver based on the a priori feasibility criteria. Enhancing recruitment and adherence in a definitive trial will require designs that promote convenience and consider ECS-reported barriers. TRIAL REGISTRATION NUMBER: NCT02433080; Pre-results. TRIAL FUNDING: University College London, St. Bartholomew's Hospital Nurses League, and NIHR University College London Hospitals Biomedical Research Centre. PMID- 28993395 TI - Single-centre retrospective analysis of growth hormone supplementation in IVF patients classified as poor-prognosis. AB - BACKGROUND: Patients undergoing in vitro fertilisation (IVF) receive various adjuvant therapies in order to enhance success rates, but the true benefit is actively debated. Growth hormone (GH) supplementation was assessed in poor prognosis women undergoing fresh IVF transfer cycles. METHODS: Data were retrospectively analysed from 400 IVF cycles, where 161 women received GH and 239 did not. RESULTS: Clinical pregnancy, live birth rates and corresponding ORs and CIs were significantly greater with GH, despite patients being significantly older with lower ovarian reserve. Patient's age, quality of transferred embryo and GH were the only significant independent predictors of clinical pregnancy (OR: 0.90, 5.00 and 2.49, p<0.002, respectively) and live birth chance (OR: 0.91, 3.90 and 4.75, p<0.014, respectively). GH increased clinical pregnancy chance by 3.42-fold (95% CI 1.82 to 6.44, p<0.0005) and live birth chance by 6.16-fold (95% CI 2.83 to 13.39, p<0.0005) after adjustment for maternal age, antral follicle count and transferred embryo quality. CONCLUSION: These data provided further evidence to indicate that GH may support more live births, particularly in younger women. It also appears that embryos generated under GH have a better implantation potential, but whether the biological mechanism is embryo-mediated or endometrium-mediated is unclear. PMID- 28993396 TI - Sensing interstitial glucose to nudge active lifestyles (SIGNAL): feasibility of combining novel self-monitoring technologies for persuasive behaviour change. AB - INTRODUCTION: Increasing physical activity (PA) reduces the risk of developing diabetes, highlighting the role of preventive medicine approaches. Changing lifestyle behaviours is difficult and is often predicated on the assumption that individuals are willing to change their lifestyles today to reduce the risk of developing disease years or even decades later. The self-monitoring technologies tested in this study will present PA feedback in real time, parallel with acute physiological data. Presenting the immediate health benefits of being more physically active may help enact change by observing the immediate consequences of that behaviour. The present study aims to assess user engagement with the self monitoring technologies in individuals at moderate-to-high risk of developing type 2 diabetes. METHODS AND ANALYSIS: 45 individuals with a moderate-to-high risk, aged >=40 years old and using a compatible smartphone, will be invited to take part in a 7-week protocol. Following 1 week of baseline measurements, participants will be randomised into one of three groups: group 1- glucose feedback followed by biobehavioural feedback (glucose plus PA); group 2-PA feedback followed by biobehavioural feedback; group 3-biobehavioural feedback. A PA monitor and a flash glucose monitor will be deployed during the intervention. Participants will wear both devices throughout the intervention but blinded to feedback depending on group allocation. The primary outcome is the level of participant engagement and will be assessed by device use and smartphone usage. Feasibility will be assessed by the practicality of the technology and screening for diabetes risk. Semistructured interviews will be conducted to explore participant experiences using the technologies. TRIAL REGISTRATION NUMBER: ISRCTN17545949. Registered on 15/05/2017. PMID- 28993397 TI - Graf regulates hematopoiesis through GEEC endocytosis of EGFR. AB - GTPase regulator associated with focal adhesion kinase 1 (GRAF1) is an essential component of the GPI-enriched endocytic compartment (GEEC) endocytosis pathway. Mutations in the human GRAF1 gene are associated with acute myeloid leukemia, but its normal role in myeloid cell development remains unclear. We show that Graf, the Drosophila ortholog of GRAF1, is expressed and specifically localizes to GEEC endocytic membranes in macrophage-like plasmatocytes. We also find that loss of Graf impairs GEEC endocytosis, enhances EGFR signaling and induces a plasmatocyte overproliferation phenotype that requires the EGFR signaling cascade. Mechanistically, Graf-dependent GEEC endocytosis serves as a major route for EGFR internalization at high, but not low, doses of the predominant Drosophila EGFR ligand Spitz (Spi), and is indispensable for efficient EGFR degradation and signal attenuation. Finally, Graf interacts directly with EGFR in a receptor ubiquitylation-dependent manner, suggesting a mechanism by which Graf promotes GEEC endocytosis of EGFR at high Spi. Based on our findings, we propose a model in which Graf functions to downregulate EGFR signaling by facilitating Spi induced receptor internalization through GEEC endocytosis, thereby restraining plasmatocyte proliferation. PMID- 28993398 TI - The African Zika virus MR-766 is more virulent and causes more severe brain damage than current Asian lineage and dengue virus. AB - The Zika virus (ZIKV) has two lineages, Asian and African, and their impact on developing brains has not been compared. Dengue virus (DENV) is a close family member of ZIKV and co-circulates with ZIKV. Here, we performed intracerebral inoculation of embryonic mouse brains with dengue virus 2 (DENV2), and found that DENV2 is sufficient to cause smaller brain size due to increased cell death in neural progenitor cells (NPCs) and neurons. Compared with the currently circulating Asian lineage of ZIKV (MEX1-44), DENV2 grows slower, causes less neuronal death and fails to cause postnatal animal death. Surprisingly, our side by-side comparison uncovered that the African ZIKV isolate (MR-766) is more potent at causing brain damage and postnatal lethality than MEX1-44. In comparison with MEX1-44, MR-766 grows faster in NPCs and in the developing brain, and causes more pronounced cell death in NPCs and neurons, resulting in more severe neuronal loss. Together, these results reveal that DENV2 is sufficient to cause smaller brain sizes, and suggest that the ZIKV African lineage is more toxic and causes more potent brain damage than the Asian lineage. PMID- 28993401 TI - Diagnosis and Management of Noncardiac Complications in Adults With Congenital Heart Disease: A Scientific Statement From the American Heart Association. AB - Life expectancy and quality of life for those born with congenital heart disease (CHD) have greatly improved over the past 3 decades. While representing a great advance for these patients, who have been able to move from childhood to successful adult lives in increasing numbers, this development has resulted in an epidemiological shift and a generation of patients who are at risk of developing chronic multisystem disease in adulthood. Noncardiac complications significantly contribute to the morbidity and mortality of adults with CHD. Reduced survival has been documented in patients with CHD with renal dysfunction, restrictive lung disease, anemia, and cirrhosis. Furthermore, as this population ages, atherosclerotic cardiovascular disease and its risk factors are becoming increasingly prevalent. Disorders of psychosocial and cognitive development are key factors affecting the quality of life of these individuals. It is incumbent on physicians who care for patients with CHD to be mindful of the effects that disease of organs other than the heart may have on the well-being of adults with CHD. Further research is needed to understand how these noncardiac complications may affect the long-term outcome in these patients and what modifiable factors can be targeted for preventive intervention. PMID- 28993399 TI - Myc cooperates with beta-catenin to drive gene expression in nephron progenitor cells. AB - For organs to achieve their proper size, the processes of stem cell renewal and differentiation must be tightly regulated. We previously showed that in the developing kidney, Wnt9b regulates distinct beta-catenin-dependent transcriptional programs in the renewing and differentiating populations of the nephron progenitor cells. How beta-catenin stimulated these two distinct programs was unclear. Here, we show that beta-catenin cooperates with the transcription factor Myc to activate the progenitor renewal program. Although in multiple contexts Myc is a target of beta-catenin, our characterization of a cell type specific enhancer for the Wnt9b/beta-catenin target gene Fam19a5 shows that Myc and beta-catenin cooperate to activate gene expression controlled by this element. This appears to be a more general phenomenon as we find that Myc is required for the expression of every Wnt9b/beta-catenin progenitor renewal target assessed as well as for proper nephron endowment in vivo This study suggests that, within the developing kidney, tissue-specific beta-catenin activity is regulated by cooperation with cell type-specific transcription factors. This finding not only provides insight into the regulation of beta-catenin target genes in the developing kidney, but will also advance our understanding of progenitor cell renewal in other cell types/organ systems in which Myc and beta catenin are co-expressed. PMID- 28993400 TI - Talin regulates integrin beta1-dependent and -independent cell functions in ureteric bud development. AB - Kidney collecting system development requires integrin-dependent cell extracellular matrix interactions. Integrins are heterodimeric transmembrane receptors consisting of alpha and beta subunits; crucial integrins in the kidney collecting system express the beta1 subunit. The beta1 cytoplasmic tail has two NPxY motifs that mediate functions by binding to cytoplasmic signaling and scaffolding molecules. Talins, scaffolding proteins that bind to the membrane proximal NPxY motif, are proposed to activate integrins and to link them to the actin cytoskeleton. We have defined the role of talin binding to the beta1 proximal NPxY motif in the developing kidney collecting system in mice that selectively express a Y-to-A mutation in this motif. The mice developed a hypoplastic dysplastic collecting system. Collecting duct cells expressing this mutation had moderate abnormalities in cell adhesion, migration, proliferation and growth factor-dependent signaling. In contrast, mice lacking talins in the developing ureteric bud developed kidney agenesis and collecting duct cells had severe cytoskeletal, adhesion and polarity defects. Thus, talins are essential for kidney collecting duct development through mechanisms that extend beyond those requiring binding to the beta1 integrin subunit NPxY motif. PMID- 28993403 TI - Cognitive and contextual factors to optimise clinical outcomes in tendinopathy. PMID- 28993402 TI - Exercise Intolerance in Heart Failure With Preserved Ejection Fraction: Diagnosing and Ranking Its Causes Using Personalized O2 Pathway Analysis. AB - BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a common syndrome with a pressing shortage of therapies. Exercise intolerance is a cardinal symptom of HFpEF, yet its pathophysiology remains uncertain. METHODS: We investigated the mechanism of exercise intolerance in 134 patients referred for cardiopulmonary exercise testing: 79 with HFpEF and 55 controls. We performed cardiopulmonary exercise testing with invasive monitoring to measure hemodynamics, blood gases, and gas exchange during exercise. We used these measurements to quantify 6 steps of oxygen transport and utilization (the O2 pathway) in each patient with HFpEF, identifying the defective steps that impair each one's exercise capacity (peak Vo2). We then quantified the functional significance of each O2 pathway defect by calculating the improvement in exercise capacity a patient could expect from correcting the defect. RESULTS: Peak Vo2 was reduced by 34+/-2% (mean+/-SEM, P<0.001) in HFpEF compared with controls of similar age, sex, and body mass index. The vast majority (97%) of patients with HFpEF harbored defects at multiple steps of the O2 pathway, the identity and magnitude of which varied widely. Two of these steps, cardiac output and skeletal muscle O2 diffusion, were impaired relative to controls by an average of 27+/-3% and 36+/-2%, respectively (P<0.001 for both). Due to interactions between a given patient's defects, the predicted benefit of correcting any single one was often minor; on average, correcting a patient's cardiac output led to a 7+/-0.5% predicted improvement in exercise intolerance, whereas correcting a patient's muscle diffusion capacity led to a 27+/-1% improvement. At the individual level, the impact of any given O2 pathway defect on a patient's exercise capacity was strongly influenced by comorbid defects. CONCLUSIONS: Systematic analysis of the O2 pathway in HFpEF showed that exercise capacity was undermined by multiple defects, including reductions in cardiac output and skeletal muscle diffusion capacity. An important source of disease heterogeneity stemmed from variation in each patient's personal profile of defects. Personalized O2 pathway analysis could identify patients most likely to benefit from treating a specific defect; however, the system properties of O2 transport favor treating multiple defects at once, as with exercise training. PMID- 28993404 TI - An internet-supported school physical activity intervention in low socioeconomic status communities: results from the Activity and Motivation in Physical Education (AMPED) cluster randomised controlled trial. AB - OBJECTIVE: Quality physical education (PE) is the cornerstone of comprehensive school physical activity (PA) promotion programmes. We tested the efficacy of a teacher professional learning intervention, delivered partially via the internet, designed to maximise opportunities for students to be active during PE lessons and enhance adolescents' motivation towards PE and PA. METHODS: A two-arm cluster randomised controlled trial with teachers and Grade 8 students from secondary schools in low socioeconomic areas of Western Sydney, Australia. The Activity and Motivation in Physical Education (AMPED) intervention for secondary school PE teachers included workshops, online learning, implementation tasks and mentoring sessions. The primary outcome was the proportion of PE lesson time that students spent in moderate-to-vigorous physical activity (MVPA), measured by accelerometers at baseline, postintervention (7-8 months after baseline) and maintenance (14-15 months). Secondary outcomes included observed PE teachers' behaviour during lessons, students' leisure-time PA and students' motivation. RESULTS: Students (n=1421) from 14 schools completed baseline assessments and were included in linear mixed model analyses. The intervention had positive effects on students' MVPA during lessons. At postintervention, the adjusted mean difference in the proportion of lesson time spent in MVPA was 5.58% (p<0.001, approximately 4 min/lesson). During the maintenance phase, this effect was 2.64% (p<0.001, approximately 2 min/lesson). The intervention had positive effects on teachers' behaviour, but did not impact students' motivation. CONCLUSIONS: AMPED produced modest improvements in MVPA and compares favourably with previous interventions delivered exclusively face-to-face. Online teacher training could help facilitate widespread dissemination of professional learning interventions. TRIAL REGISTRATION NUMBER: ACTRN12614000184673. PMID- 28993405 TI - Do physical conditioning programmes reduce work absenteeism related to back pain? (PEDro synthesis). PMID- 28993407 TI - Heterozygous Null LDLR Mutation in a Familial Hypercholesterolemia Patient With an Atypical Presentation Because of Alcohol Abuse. PMID- 28993406 TI - Heritability of Mitral Regurgitation: Observations From the Framingham Heart Study and Swedish Population. AB - BACKGROUND: Familial aggregation has been described for primary mitral regurgitation (MR) caused by mitral valve prolapse. We hypothesized that heritability of MR exists across different MR subtypes including nonprimary MR. METHODS AND RESULTS: Study participants were FHS (Framingham Heart Study) Generation 3 (Gen 3) and Gen 2 cohort participants and all adult Swedish siblings born after 1932 identified in 1997 and followed through 2010. MR was defined as >= mild regurgitation on color Doppler in FHS and from International Classification of Diseases codes in Sweden. We estimated the association of sibling MR with MR in Gen 2/Gen 3/Swedish siblings. We also estimated heritability of MR in 539 FHS pedigrees (7580 individuals). Among 5132 FHS Gen 2/Gen 3 participants with sibling information, 1062 had MR. Of siblings with sibling MR, 28% (500/1797) had MR compared with 17% (562/3335) without sibling MR (multivariable-adjusted odds ratio, 1.20; 95% confidence interval [CI], 1.01 1.43; P=0.04). When we combined parental and sibling data in FHS pedigrees, heritability of MR was estimated at 0.15 (95% CI, 0.07-0.23), 0.12 (95% CI, 0.04 0.20) excluding mitral valve prolapse, and 0.44 (95% CI, 0.15-0.73) for >= moderate MR only (all P<0.05). In Sweden, sibling MR was associated with a hazard ratio of 3.57 (95% CI, 2.21-5.76; P<0.001) for development of MR. CONCLUSIONS: Familial clustering of MR exists in the community, supporting a genetic susceptibility common to primary and nonprimary MR. Further studies are needed to elucidate the common regulatory pathways that may lead to MR irrespective of its cause. PMID- 28993408 TI - Inheritance Impacts Mitral Valve Insufficiency. PMID- 28993409 TI - MALT1 Inhibition Is Efficacious in Both Naive and Ibrutinib-Resistant Chronic Lymphocytic Leukemia. AB - The clinical efficacy displayed by ibrutinib in chronic lymphocytic leukemia (CLL) has been challenged by the frequent emergence of resistant clones. The ibrutinib target, Bruton's tyrosine kinase (BTK), is essential for B-cell receptor signaling, and most resistant cases carry mutations in BTK or PLCG2, a downstream effector target of BTK. Recent findings show that MI-2, a small molecule inhibitor of the para-caspase MALT1, is effective in preclinical models of another type of BCR pathway-dependent lymphoma. We therefore studied the activity of MI-2 against CLL and ibrutinib-resistant CLL. Treatment of CLL cells in vitro with MI-2 inhibited MALT1 proteolytic activity reduced BCR and NF-kappaB signaling, inhibited nuclear translocation of RelB and p50, and decreased Bcl-xL levels. MI-2 selectively induced dose and time-dependent apoptosis in CLL cells, sparing normal B lymphocytes. Furthermore, MI-2 abrogated survival signals provided by stromal cells and BCR cross-linking and was effective against CLL cells harboring features associated with poor outcomes, including 17p deletion and unmutated IGHV Notably, MI-2 was effective against CLL cells collected from patients harboring mutations conferring resistance to ibrutinib. Overall, our findings provide a preclinical rationale for the clinical development of MALT1 inhibitors in CLL, in particular for ibrutinib-resistant forms of this disease. Cancer Res; 77(24); 7038-48. (c)2017 AACR. PMID- 28993410 TI - PACE4 Undergoes an Oncogenic Alternative Splicing Switch in Cancer. AB - Inhibition of PACE4, a proprotein convertase that is overexpressed in prostate cancer, has been shown to block cancer progression in an androgen-independent manner. However, the basis for its overexpression and its growth-inhibitory effects are mitigated and uncertain. Here, we report that PACE4 pre-mRNA undergoes DNA methylation-sensitive alternative splicing of its terminal exon 3' untranslated region, generating an oncogenic, C-terminally modified isoform (PACE4-altCT). We found this isoform to be strongly expressed in prostate cancer cells, where it displayed an enhanced autoactivating process and a distinct intracellular routing that prevented its extracellular secretion. Together, these events led to a dramatic increase in processing of the progrowth differentiation factor pro-GDF15 as the first PACE4 substrate to be identified in prostate cancer. We detected robust expression of PACE4-altCT in other cancer types, suggesting that an oncogenic switch for this proenzyme may offer a therapeutic target not only in advanced prostate cancer but perhaps also more broadly in human cancer. Cancer Res; 77(24); 6863-79. (c)2017 AACR. PMID- 28993413 TI - Moonshot Acceleration Factor: Medical Imaging. AB - Medical imaging is essential to screening, early diagnosis, and monitoring responses to cancer treatments and, when used with other diagnostics, provides guidance for clinicians in choosing the most effective patient management plan that maximizes survivorship and quality of life. At a gathering of agency officials, patient advocacy organizations, industry/professional stakeholder groups, and clinical/basic science academicians, recommendations were made on why and how one should build a "cancer knowledge network" that includes imaging. Steps to accelerate the translation and clinical adoption of cancer discoveries to meet the goals of the Cancer Moonshot include harnessing computational power and architectures, developing data sharing policies, and standardizing medical imaging and in vitro diagnostics. Cancer Res; 77(21); 5717-20. (c)2017 AACR. PMID- 28993411 TI - Sleeping Beauty Insertional Mutagenesis in Mice Identifies Drivers of Steatosis Associated Hepatic Tumors. AB - Hepatic steatosis is a strong risk factor for the development of hepatocellular carcinoma (HCC), yet little is known about the molecular pathology associated with this factor. In this study, we performed a forward genetic screen using Sleeping Beauty (SB) transposon insertional mutagenesis in mice treated to induce hepatic steatosis and compared the results to human HCC data. In humans, we determined that steatosis increased the proportion of female HCC patients, a pattern also reflected in mice. Our genetic screen identified 203 candidate steatosis-associated HCC genes, many of which are altered in human HCC and are members of established HCC-driving signaling pathways. The protein kinase A/cyclic AMP signaling pathway was altered frequently in mouse and human steatosis-associated HCC. We found that activated PKA expression drove steatosis specific liver tumorigenesis in a mouse model. Another candidate HCC driver, the N-acetyltransferase NAT10, which we found to be overexpressed in human steatosis associated HCC and associated with decreased survival in human HCC, also drove liver tumorigenesis in a steatotic mouse model. This study identifies genes and pathways promoting HCC that may represent novel targets for prevention and treatment in the context of hepatic steatosis, an area of rapidly growing clinical significance. Cancer Res; 77(23); 6576-88. (c)2017 AACR. PMID- 28993412 TI - IL10 Release upon PD-1 Blockade Sustains Immunosuppression in Ovarian Cancer. AB - Ligation of programmed cell death-1 (PD-1) in the tumor microenvironment is known to inhibit effective adaptive antitumor immunity. Blockade of PD-1 in humans has resulted in impressive, durable regression responses in select tumor types. However, durable responses have been elusive in ovarian cancer patients. PD-1 was recently shown to be expressed on and thereby impair the functions of tumor infiltrating murine and human myeloid dendritic cells (TIDC) in ovarian cancer. In the present work, we characterize the regulation of PD-1 expression and the effects of PD-1 blockade on TIDC. Treatment of TIDC and bone marrow-derived dendritic cells (DC) with IL10 led to increased PD-1 expression. Both groups of DCs also responded to PD-1 blockade by increasing production of IL10. Similarly, treatment of ovarian tumor-bearing mice with PD-1 blocking antibody resulted in an increase in IL10 levels in both serum and ascites. While PD-1 blockade or IL10 neutralization as monotherapies were inefficient, combination of these two led to improved survival and delayed tumor growth; this was accompanied by augmented antitumor T- and B-cell responses and decreased infiltration of immunosuppressive MDSC. Taken together, our findings implicate compensatory release of IL10 as one of the adaptive resistance mechanisms that undermine the efficacy of anti-PD-1 (or anti-PD-L1) monotherapies and prompt further studies aimed at identifying such resistance mechanisms. Cancer Res; 77(23); 6667-78. (c)2017 AACR. PMID- 28993414 TI - A Collaborative Model for Accelerating the Discovery and Translation of Cancer Therapies. AB - Preclinical studies using genetically engineered mouse models (GEMM) have the potential to expedite the development of effective new therapies; however, they are not routinely integrated into drug development pipelines. GEMMs may be particularly valuable for investigating treatments for less common cancers, which frequently lack alternative faithful models. Here, we describe a multicenter cooperative group that has successfully leveraged the expertise and resources from philanthropic foundations, academia, and industry to advance therapeutic discovery and translation using GEMMs as a preclinical platform. This effort, known as the Neurofibromatosis Preclinical Consortium (NFPC), was established to accelerate new treatments for tumors associated with neurofibromatosis type 1 (NF1). At its inception, there were no effective treatments for NF1 and few promising approaches on the horizon. Since 2008, participating laboratories have conducted 95 preclinical trials of 38 drugs or combinations through collaborations with 18 pharmaceutical companies. Importantly, these studies have identified 13 therapeutic targets, which have inspired 16 clinical trials. This review outlines the opportunities and challenges of building this type of consortium and highlights how it can accelerate clinical translation. We believe that this strategy of foundation-academic-industry partnering is generally applicable to many diseases and has the potential to markedly improve the success of therapeutic development. Cancer Res; 77(21); 5706-11. (c)2017 AACR. PMID- 28993415 TI - Targeting either GH or IGF-I during somatostatin analogue treatment in patients with acromegaly: a randomized multicentre study. AB - CONTEXT: Discordant GH and IGF-I values are frequent in acromegaly. The clinical significance and its dependence on treatment modality and of glucose-suppressed GH (GHnadir) measurements remain uncertain. OBJECTIVE: To evaluate the effects of targeting either IGF-I or GH during somatostatin analogue (SA) treatment. PATIENTS AND METHODS: 84 patients with controlled acromegaly after surgery (n = 23) or SA (n = 61) underwent a GH profile including an OGTT, at baseline and after 12 months. SA patients were randomized to monitoring according to either IGF-I (n = 33) or GHnadir (n = 28). SA dose escalation was allowed at baseline and 6 months. MAIN OUTCOME MEASURES: GHnadir and IGF-I at baseline and 12 months, and disease-specific Quality of Life (QoL). RESULTS: IGF-I and fasting GH levels were comparable between the surgery and the SA group, whereas GHnadir (ug/L) was lower in the surgery group (GHnadir 0.7 +/- 0.1 vs 0.3 +/- 0.1, P < 0.01). SA dose increase was performed in 20 patients in the GH group and in 8 patients in the IGF-I group (P = 0.02), which increased the number of concordantly controlled patients (P = 0.01). QoL was only mildly affected at baseline in all groups and did not changed consistently during the study. CONCLUSION: (1) Discordant values in terms of high GH levels are prevalent in SA patients and more so if applying glucose-suppressed GHnadir; (2) targeting discordant levels of either GH or IGF-I translates into SA dose increase and improved biochemical control; (3) even though QoL was not improved in this study, we suggest biochemical assessment of disease activity to include glucose-suppressed GHnadir also in SA patients. PMID- 28993417 TI - Proton pump inhibitor use associated with changes in gut microbiota composition. PMID- 28993416 TI - Regulation of Axon Guidance by the Wnt Receptor Ror/CAM-1 in the PVT Guidepost Cell in Caenorhabditis elegans. AB - The Caenorhabditis elegans ventral nerve cord (VNC) consists of two asymmetric bundles of neurons and axons that are separated by the midline. How the axons are guided to stay on the correct sides of the midline remains poorly understood. Here we provide evidence that the conserved Wnt signaling pathway along with the Netrin and Robo pathways constitute a combinatorial code for midline guidance of PVP and PVQ axons that extend into the VNC. Combined loss of the Wnts CWN-1, CWN 2, and EGL-20 or loss of the Wnt receptor CAM-1 caused >70% of PVP and PVQ axons to inappropriately cross over from the left side to the right side. Loss of the Frizzled receptor LIN-17 or the planar cell polarity (PCP) protein VANG-1 also caused cross over defects that did not enhance those in the cam-1 mutant, indicating that the proteins function together in midline guidance. Strong cam-1 expression can be detected in the PVQs and the guidepost cell PVT that is located on the midline. However, only when cam-1 is expressed in PVT are the crossover defects of PVP and PVQ rescued, showing that CAM-1 functions nonautonomously in PVT to prevent axons from crossing the midline. PMID- 28993418 TI - A genetic roadmap of pancreatic cancer: still evolving. AB - A diagnosis of pancreatic ductal adenocarcinoma (PDA) is often fatal. PDA is widely recognised as one of the 'incurable cancers' because therapies against this tumour type are generally ineffective. The fatal nature of this tumour is due to its aggressive clinical course. Pancreatic cancer commonly presents at the metastatic stage; even in cases where tumours are localised to the pancreas at diagnosis, metastatic seeds have often been invariably been spawned off, frustrating surgical attempts to cure the cancer. The key principles of pancreatic cancer mutational development were outlined nearly two decades ago using the genetics of precursor lesions to position the various stages of tumour progression. Since then, there has been a cavalcade of new data. How these recent studies impact the classical perceptions of pancreatic cancer development is a work in progress. Given that significant improvements in patient outcomes are not in sight for this disease, it is likely that broadening the current perspectives and acquiring deeper biological insights into the morphogenetic route of tumour development will be needed to foster new strategies for more effective cancer control. PMID- 28993419 TI - Quantitative Profiling of N-linked Glycosylation Machinery in Yeast Saccharomyces cerevisiae. AB - Asparagine-linked glycosylation is a common posttranslational protein modification regulating the structure, stability and function of many proteins. The N-linked glycosylation machinery involves enzymes responsible for the assembly of the lipid-linked oligosaccharide (LLO), which is then transferred to the asparagine residues on the polypeptides by the enzyme oligosaccharyltransferase (OST). A major goal in the study of protein glycosylation is to establish quantitative methods for the analysis of site specific extent of glycosylation. We developed a sensitive approach to examine glycosylation site occupancy in Saccharomyces cerevisiae by coupling stable isotope labeling (SILAC) approach to parallel reaction monitoring (PRM) mass spectrometry (MS). We combined the method with genetic tools and validated the approach with the identification of novel glycosylation sites dependent on the Ost3p and Ost6p regulatory subunits of OST. Based on the observations that alternations in LLO substrate structure and OST subunits activity differentially alter the systemic output of OST, we conclude that sequon recognition is a direct property of the catalytic subunit Stt3p, auxiliary subunits such as Ost3p and Ost6p extend the OST substrate range by modulating interfering pathways such as protein folding. In addition, our proteomics approach revealed a novel regulatory network that connects isoprenoid lipid biosynthesis and LLO substrate assembly. PMID- 28993420 TI - Two-Step Sequential Approach for Concomitant Skin and Soft Tissue Infection and Osteomyelitis Complicating the Diabetic Foot. PMID- 28993422 TI - Comments on Durante's account of multiculturalism. PMID- 28993421 TI - Burden of Mortality Attributable to Diagnosed Diabetes: A Nationwide Analysis Based on Claims Data From 65 Million People in Germany. AB - OBJECTIVE: In Germany, as in many other countries, nationwide data on mortality attributable to diagnosed diabetes are not available. This study estimated the absolute number of excess deaths associated with diabetes (all types) and type 2 diabetes in Germany. RESEARCH DESIGN AND METHODS: A prevalence approach that included nationwide routine data from 64.9 million people insured in the German statutory health insurance system in 2010 was used for the calculation. Because nationwide data on diabetes mortality are lacking in Germany, the mortality rate ratio from the Danish National Diabetes Register was used. The absolute number of excess deaths associated with diabetes was calculated as the number of deaths due to diabetes minus the number of deaths due to diabetes with a mortality that was as high as in the population without diabetes. Furthermore, the mortality population-attributable fraction was calculated. RESULTS: A total of 174,627 excess deaths were due to diabetes in 2010, including 137,950 due to type 2 diabetes. Overall, 21% of all deaths in Germany were attributable to diabetes and 16% were attributable to type 2 diabetes. Most of the excess deaths (34% each) occurred in the 70- to 89-year-old age-group. CONCLUSIONS: In this first nationwide calculation of excess deaths related to diabetes in Germany, the results suggest that the official German estimates that rely on information from death certificates are grossly underestimated. Countries without national cohorts or diabetes registries could easily use this method to estimate the number of excess deaths due to diabetes. PMID- 28993423 TI - Against lifetime QALY prioritarianism. AB - Lifetime quality-adjusted life-year (QALY) prioritarianism has recently been defended as a reasonable specification of the prioritarian view that benefits to the worse off should be given priority in health-related priority setting. This paper argues against this view with reference to how it relies on implausible assumptions. By referring to lifetime QALY as the basis for judgments about who is worse off lifetime QALY prioritarianism relies on assumptions of strict additivity, atomism and intertemporal separability of sublifetime attributes. These assumptions entail that a health state at some period in time contributes with the same amount to how well off someone is regardless of intrapersonal and interpersonal distributions of health states. The paper argues that this is implausible and that prioritarians should take both intrapersonal and interpersonal distributions of goods into account when they establish who is worse off. They should therefore not accept that lifetime QALY is a reasonable ground for ascribing priority and reject lifetime QALY prioritarianism. PMID- 28993424 TI - Competition, cooperation and human flourishing: commentary on Koch. PMID- 28993425 TI - Wrist mass in a 93-year-old woman. AB - CLINICAL INTRODUCTION: A 93-year-old woman presented electively for transaortic valve implantation (TAVI), for severe aortic stenosis. She had a history of hypertension and hypothyroidism, and she was taking clopidogrel, antihypertensives and levothyroxine. In preparation for her TAVI procedure she underwent coronary angiography 4 months previously. Her coronary angiogram revealed severe three vessel disease, however, the consensus from the multidisciplinary team meeting, at that time, was to manage the coronary disease medically. Physical examination revealed a large, non-tender swelling on the volar aspect of her wrist (figure 1). The swelling had progressively enlarged in size over the preceding 4 months. Duplex ultrasonography was performed, but was technically difficult. Turbulent bidirectional flow was seen within the wrist swelling, however the connecting tract from which the flow originated was not adequately visualised. The greyscale ultrasound is shown (figure 1).heartjnl;104/5/437/F1F1F1Figure 1The panel on the left shows the swelling on the volar aspect of the wrist. The panel on the right shows the grey scale ultrasound image of the swelling at the wrist. QUESTION : What is the next most appropriate management step?Antibiotics and drainageUrgent ultrasound guided thrombin injectionNon-emergent vascular surgeryConservative management, with observation and follow-upUltrasound guided compression. PMID- 28993426 TI - Effect of diabetes status and hyperglycemia on global DNA methylation and hydroxymethylation. AB - Type 2 diabetes mellitus (T2DM) is characterized by oxidative stress that could lead to chronic micro- and macrovascular complications. We hypothesized that some of the target organ damage is mediated by oxidative alterations in epigenetic mechanisms involving DNA methylation (5mC) and DNA hydroxymethylation (5hmC). We analyzed global DNA methylation and hydroxymethylation in peripheral blood cells in well-controlled and poorly controlled patients with T2DM and compared them with healthy controls. We also analyzed microarrays of DNA methylation and gene expression of other important tissues in the context of diabetes from the GEO database repository and then compared these results with our experimental gene expression data. DNA methylation and, more importantly, DNA hydroxymethylation levels were increased in poorly controlled patients compared to well-controlled and healthy individuals. Both 5mC and 5hmC measurements were correlated with the percentage of glycated hemoglobin, indicating a direct impact of hyperglycemia on changes over the epigenome. The analysis of methylation microarrays was concordant, and 5mC levels were increased in the peripheral blood of T2DM patients. However, the DNA methylation levels were the opposite of those in other tissues, such as the pancreas, adipose tissue and skeletal muscle. We hypothesize that a process of DNA oxidation associated with hyperglycemia may explain the DNA demethylation in which the activity of ten-eleven translocation (TET) proteins is not sufficient to complete the process. High levels of glucose lead to cellular oxidation, which triggers the process of DNA demethylation aided by TET enzymes, resulting in epigenetic dysregulation of the damaged tissues. PMID- 28993427 TI - Fate and the clinic: a multidisciplinary consideration of fatalism in health behaviour. AB - The role of fatalism in health behaviour has stirred significant controversy in literature across several disciplines. Some researchers have demonstrated a negative correlation between fatalistic beliefs and healthy behaviours such as cancer screening, arguing that fatalism is a barrier to health-seeking behaviours. Other studies have painted a more complicated picture of fatalistic beliefs and health behaviours that ultimately questions fatalism's causality as a distinct factor. Unpacking this debate raises thought-provoking questions about how epistemological and methodological frameworks present particular pictures about the connections between belief, race, class and behaviour. The discussion surrounding fatalism illuminates larger tensions between structural and cultural determinants of health behaviour. This article argues for a more rigorous delineation of culture and structure and suggests that future theory-informed and ethnographic research may more precisely parse the role of fatalism in health attitudes, beliefs and behaviours. PMID- 28993430 TI - Baby-led weaning did not significantly impact body mass index when compared with traditional spoon-feeding. PMID- 28993431 TI - Quick-Wee is an effective technique for urine collection in infants. PMID- 28993429 TI - TGF-beta1 secreted by Tregs in lymph nodes promotes breast cancer malignancy via up-regulation of IL-17RB. AB - Lymph node (LN) metastasis is commonly associated with systemic distant organ metastasis in human breast cancer and is an important prognostic predictor for survival of breast cancer patients. However, whether tumor-draining LNs (TDLNs) play a significant role in modulating the malignancy of cancer cells for distant metastasis remains controversial. Using a syngeneic mouse mammary tumor model, we found that breast tumor cells derived from TDLN have higher malignancy and removal of TDLNs significantly reduced distant metastasis. Up-regulation of oncogenic Il-17rb in cancer cells derived from TDLNs contributes to their malignancy. TGF-beta1 secreted from regulatory T cells (Tregs) in the TDLNs mediated the up-regulation of Il-17rb through downstream Smad2/3/4 signaling. These phenotypes can be abolished by TGF-beta1 neutralization or depletion of Tregs. Consistently, clinical data showed that the up-regulation of IL-17RB in cancer cells from LN metastases correlated with the increased prevalence of Tregs as well as the aggressive growth of tumors in mouse xenograft assay. Together, these results indicate that Tregs in TDLNs play an important role in modulating the malignancy of breast cancer cells for distant metastasis. Blocking IL-17RB expression could therefore be a potential approach to curb the process. PMID- 28993432 TI - Embedding electronic growth charts into clinical practice at a children's hospital. AB - Embedding electronic growth charts (EGCs) into clinical practice in a children's hospital. We employed initial implementation in the outpatient setting and subsequently extended this across inpatients with the growth chart following the child's records through both settings and significantly increasing growth data documentation. PMID- 28993428 TI - Disease-modifying effects of ganglioside GM1 in Huntington's disease models. AB - Huntington's disease (HD) is a progressive neurodegenerative disorder characterized by motor, cognitive and psychiatric problems. Previous studies indicated that levels of brain gangliosides are lower than normal in HD models and that administration of exogenous ganglioside GM1 corrects motor dysfunction in the YAC128 mouse model of HD In this study, we provide evidence that intraventricular administration of GM1 has profound disease-modifying effects across HD mouse models with different genetic background. GM1 administration results in decreased levels of mutant huntingtin, the protein that causes HD, and in a wide array of beneficial effects that include changes in levels of DARPP32, ferritin, Iba1 and GFAP, modulation of dopamine and serotonin metabolism, and restoration of normal levels of glutamate, GABA, L-Ser and D-Ser. Treatment with GM1 slows down neurodegeneration, white matter atrophy and body weight loss in R6/2 mice. Motor functions are significantly improved in R6/2 mice and restored to normal in Q140 mice, including gait abnormalities that are often resistant to treatments. Psychiatric-like and cognitive dysfunctions are also ameliorated by GM1 administration in Q140 and YAC128 mice. The widespread benefits of GM1 administration, at molecular, cellular and behavioural levels, indicate that this ganglioside has strong therapeutic and disease-modifying potential in HD. PMID- 28993433 TI - Management of thromboembolism-in-transit with pulmonary embolism. AB - : We present a rare complication of deep venous thrombosis with pulmonary embolism that threatened the patient with systemic embolization. A 36-year-old female was referred to the hospital after five days of progressive shortness of breath and chest pain. Preceding onset of symptoms, she had undergone surgery leading to reduced physical activity and had just returned from vacation by a long flight. Investigations with transthoracic and transesophageal echocardiography revealed a thromboembolism-in-transit across a patent foramen ovale. Thoracic CT showed submassive bilateral pulmonary embolism. Hemodynamic parameters were stable. The patient was treated surgically with extraction of the thrombus, closure of the foramen ovale and removal of the bilateral pulmonary emboli. She was discharged after an uneventful hospital stay. LEARNING POINTS: Thromboembolism-in-transit across a patent foramen ovale usually occurs in the presence of deep venous thrombosis with pulmonary embolism. The abrupt rise in pulmonary arterial pressure may contribute to the migration of the thrombus across the atrial septum to the systemic circulation.If any abnormal structures are seen in the left atrium by TTE in a patient with pulmonary embolism, a TEE should be performed to rule out an embolus entrapped in a patent foramen ovale.When acute pulmonary hypertension cannot be assessed by conventional methods, additional parameters such as shortened right ventricular outflow tract acceleration time and a mid-systolic notching of the pulse wave Doppler profile in the right ventricular outflow tract may be useful.Mortality is highest during the initial 24 h after onset of chest symptoms; thus, optimal treatment must commence urgently.The choice of treatment in each individual patient must be made after a thorough discussion in a multidisciplinary heart team. PMID- 28993434 TI - Inherited mutations in BRCA1 and BRCA2 in an unselected multiethnic cohort of Asian patients with breast cancer and healthy controls from Malaysia. AB - BACKGROUND: Genetic testing for BRCA1 and BRCA2 is offered typically to selected women based on age of onset and family history of cancer. However, current internationally accepted genetic testing referral guidelines are built mostly on data from cancer genetics clinics in women of European descent. To evaluate the appropriateness of such guidelines in Asians, we have determined the prevalence of germ line variants in an unselected cohort of Asian patients with breast cancer and healthy controls. METHODS: Germ line DNA from a hospital-based study of 2575 unselected patients with breast cancer and 2809 healthy controls were subjected to amplicon-based targeted sequencing of exonic and proximal splice site junction regions of BRCA1 and BRCA2 using the Fluidigm Access Array system, with sequencing conducted on a Illumina HiSeq2500 platform. Variant calling was performed with GATK UnifiedGenotyper and were validated by Sanger sequencing. RESULTS: Fifty-five (2.1%) BRCA1 and 66 (2.6%) BRCA2 deleterious mutations were identified among patients with breast cancer and five (0.18%) BRCA1 and six (0.21%) BRCA2 mutations among controls. One thousand one hundred and eighty-six (46%) patients and 97 (80%) carriers fulfilled the National Comprehensive Cancer Network guidelines for genetic testing. CONCLUSION: Five per cent of unselected Asian patients with breast cancer carry deleterious variants in BRCA1 or BRCA2. While current referral guidelines identified the majority of carriers, one in two patients would be referred for genetic services. Given that such services are largely unavailable in majority of low-resource settings in Asia, our study highlights the need for more efficient guidelines to identify at-risk individuals in Asia. PMID- 28993435 TI - Impact of intercurrent illness on calcium homeostasis in children with hypoparathyroidism: a case series. AB - BACKGROUND: Hypoparathyroidism is characterised by hypocalcaemia, and standard management is with an active vitamin D analogue and adequate oral calcium intake (dietary and/or supplements). Little is described in the literature about the impact of intercurrent illnesses on calcium homeostasis in children with hypoparathyroidism. METHODS: We describe three children with hypoparathyroidism in whom intercurrent illnesses led to hypocalcaemia and escalation of treatment with alfacalcidol (1-hydroxycholecalciferol) and calcium supplements. RESULTS: Three infants managed with standard treatment for hypoparathyroidism (two with homozygous mutations in GCMB2 gene and one with Sanjad-Sakati syndrome) developed symptomatic hypocalcaemia (two infants developed seizures) following respiratory or gastrointestinal illnesses. Substantial increases in alfacalcidol doses (up to three times their pre-illness doses) and calcium supplementation were required to achieve acceptable serum calcium concentrations. However, following resolution of illness, these children developed an increase in serum calcium and hypercalciuria, necessitating rapid reduction to pre-illness dosages of alfacalcidol and oral calcium supplementation. CONCLUSION: Intercurrent illness may precipitate symptomatic hypocalcaemia in children with hypoparathyroidism, necessitating increase in dosages of alfacalcidol and calcium supplements. Close monitoring is required on resolution of the intercurrent illness, with timely reduction of dosages of active analogues of vitamin D and calcium supplements to prevent hypercalcaemia, hypercalciuria and nephrocalcinosis. PMID- 28993436 TI - Efficacy of resveratrol to supplement oral nifedipine treatment in pregnancy induced preeclampsia. AB - OBJECTIVE: Preeclampsia (PE) is a complication affecting pregnant women worldwide, which usually manifests as severe maternal hypertension. Resveratrol (RESV), a naturally existing polyphenol, is known to exhibit beneficial effects in cardiovascular disease including hypertension. We evaluated the outcome of treatment combining oral nifedipine (NIFE) and RESV against PE. DESIGN AND METHODS: Using a randomized group assignment, 400 PE patients were enrolled and received oral treatments of either NIFE + RESV or NIFE + placebo. Primary endpoints were defined as time to control blood pressure and time before a new hypertensive crisis. Secondary endpoints were defined as the number of doses needed to control blood pressure, maternal and neonatal adverse effects. RESULTS: Compared with the NIFE + placebo group, the time needed to control blood pressure was significantly reduced in NIFE + RESV group, while time before a new hypertensive crisis was greatly delayed in NIFE + RESV group. The number of treatment doses needed to control blood pressure was also categorically lower in NIFE + RESV group. No differences in maternal or neonatal adverse effects were observed between the two treatment groups. CONCLUSION: Our data support the potential of RESV as a safe and effective adjuvant of oral NIFE to attenuate hypertensive symptoms among PE patients. PMID- 28993437 TI - Thyroid hormone regulates protease expression and activation of Notch signaling in implantation and embryo development. AB - A clinical association between thyroid dysfunction and pregnancy complications has been extensively reported; however, the molecular mechanisms through which TH might regulate key events of pregnancy have not been elucidated yet. In this respect, we performed in vivo studies in MMI-induced hypothyroid pregnant mice, evaluating the effect of hypothyroidism on the number of implantation sites, developing embryos/resorptions and pups per litter, at 4.5, 10.5, 18.5 days post coitum (dpc) and at birth. We also studied the expression of major molecules involved in implantation and placentation, such as the proteases ISPs, MMPs, TIMPs and Notch pathway-related genes. Our results demonstrate that hypothyroidism may have a dual effect on pregnancy, by initially influencing implantation and by regulating placental development at later stages of gestation. To further elucidate the role of TH in implantation, we performed in vitro studies by culturing 3.5 dpc blastocysts in the presence of TH, with or without endometrial cells used as the feeder layer, and studied their ability to undergo hatching and outgrowth. We observed that, in the presence of endometrial feeder cells, TH is able to anticipate blastocyst hatching by upregulating the expression of blastocyst-produced ISPs, and to enhance blastocyst outgrowth by upregulating endometrial ISPs and MMPs. These results clearly indicate that TH is involved in the bidirectional crosstalk between the competent blastocyst and the receptive endometrium at the time of implantation. PMID- 28993439 TI - Intraoperative non-technical skills: a critical target for improving surgical outcomes. PMID- 28993440 TI - Postmarket medical device safety: moving beyond voluntary reporting. PMID- 28993438 TI - Architecture and Distribution of Introns in Core Genes of Four Fusarium Species. AB - Removal of introns from transcribed RNA represents a crucial step during the production of mRNA in eukaryotes. Available whole-genome sequences and expressed sequence tags (ESTs) have increased our knowledge of this process and revealed various commonalities among eukaryotes. However, certain aspects of intron structure and diversity are taxon-specific, which can complicate the accuracy of in silico gene prediction methods. Using core genes, we evaluated the distribution and architecture of Fusarium circinatum spliceosomal introns, and linked these characteristics to the accuracy of the predicted gene models of the genome of this fungus. We also evaluated intron distribution and architecture in F. verticillioides, F. oxysporum, and F. graminearum, and made comparisons with F. circinatum Results indicated that F. circinatum and the three other Fusarium species have canonical 5' and 3' splice sites, but with subtle differences that are apparently not shared with those of other fungal genera. The polypyrimidine tract of Fusarium introns was also found to be highly divergent among species and genes. Furthermore, the conserved adenosine nucleoside required during the first step of splicing is contained within unique branch site motifs in certain Fusarium introns. Data generated here show that introns of F. circinatum, as well as F. verticillioides, F. oxysporum, and F. graminearum, are characterized by a number of unique features such as the CTHAH and ACCAT motifs of the branch site. Incorporation of such information into genome annotation software will undoubtedly improve the accuracy of gene prediction methods used for Fusarium species and related fungi. PMID- 28993441 TI - Providing feedback following Leadership WalkRounds is associated with better patient safety culture, higher employee engagement and lower burnout. AB - BACKGROUND: There is a poorly understood relationship between Leadership WalkRounds (WR) and domains such as safety culture, employee engagement, burnout and work-life balance. METHODS: This cross-sectional survey study evaluated associations between receiving feedback about actions taken as a result of WR and healthcare worker assessments of patient safety culture, employee engagement, burnout and work-life balance, across 829 work settings. RESULTS: 16 797 of 23 853 administered surveys were returned (70.4%). 5497 (32.7% of total) reported that they had participated in WR, and 4074 (24.3%) reported that they participated in WR with feedback. Work settings reporting more WR with feedback had substantially higher safety culture domain scores (first vs fourth quartile Cohen's d range: 0.34-0.84; % increase range: 15-27) and significantly higher engagement scores for four of its six domains (first vs fourth quartile Cohen's d range: 0.02-0.76; % increase range: 0.48-0.70). CONCLUSION: This WR study of patient safety and organisational outcomes tested relationships with a comprehensive set of safety culture and engagement metrics in the largest sample of hospitals and respondents to date. Beyond measuring simply whether WRs occur, we examine WR with feedback, as WR being done well. We suggest that when WRs are conducted, acted on, and the results are fed back to those involved, the work setting is a better place to deliver and receive care as assessed across a broad range of metrics, including teamwork, safety, leadership, growth opportunities, participation in decision-making and the emotional exhaustion component of burnout. Whether WR with feedback is a manifestation of better norms, or a cause of these norms, is unknown, but the link is demonstrably potent. PMID- 28993442 TI - In-room assessment of intravascular velocity from time-resolved rotational angiography in patients with arteriovenous malformation: a pilot study. AB - BACKGROUND: Time-resolved rotational angiography (t-RA) enables interventionists to better comprehend complex arteriovenous malformations (AVMs), thereby facilitating endovascular treatment. However, its use in evaluating hemodynamic changes has rarely been explored. OBJECTIVE: This study uses t-RA to estimate intravascular flow in patients with AVM to compare this with flow in the normal population. METHODS: Patients with available t-RA scans were prospectively categorized into one of three groups: hemorrhagic AVM, non-hemorrhagic AVM and control. Pulsatile time-density curves (TDCs) for C1, C6 and VOIMCA were used for amplitude and velocity estimation. C1 was at the cervical internal carotid artery (ICA), 2-3 cm below the carotid canal, C6 was at the paraclinoid segment of the ICA, and VOIMCA was at the junction of the first and second segment of the middle cerebral artery (MCA). A waveform amplitude ratio was defined as (peak - trough)/trough contrast intensity. VICA was defined as the distance between C6 and C1 divided by the time required for the wave to pass, and correspondingly, the average velocity of MCA (VMCA) was defined as the distance between C6 and VOIMCA divided by the duration for the same peak to travel from C6 and VOIMCA, AVM volume was estimated by MR angiography. RESULTS: Amplitude ratios AC1 and AC6, and average flow velocities VICA and VMCA were significantly larger in the non-hemorrhagic group than in the control group, while the hemorrhagic AVM group was not significantly different from the controls. VICA and VMCA showed moderate to good correlations with AVM volume (r=0.51 and 0.73, respectively). VMCA (33.0+/-9.1) was significantly lower than VICA (41.3+/-13.2) in the control group, but not in the two AVM groups. CONCLUSION: TDC waveform propagation derived from t-RA can quantify hemodynamic differences between AVM and the control group. t-RA provides both real-time anatomic and hemodynamic evaluation, and can thus potentially improve the interventional workflow. PMID- 28993444 TI - Immigrant Latino Children and the Limits of Questionnaires in Capturing Adverse Childhood Events. PMID- 28993443 TI - CRISPR/Cas9 screening using unique molecular identifiers. AB - Loss-of-function screening by CRISPR/Cas9 gene knockout with pooled, lentiviral guide libraries is a widely applicable method for systematic identification of genes contributing to diverse cellular phenotypes. Here, Random Sequence Labels (RSLs) are incorporated into the guide library, which act as unique molecular identifiers (UMIs) to allow massively parallel lineage tracing and lineage dropout screening. RSLs greatly improve the reproducibility of results by increasing both the precision and the accuracy of screens. They reduce the number of cells needed to reach a set statistical power, or allow a more robust screen using the same number of cells. PMID- 28993445 TI - Adverse Childhood Experiences Among Hispanic Children in Immigrant Families Versus US-Native Families. AB - OBJECTIVES: To examine the prevalence of child and family characteristics associated with adverse childhood experiences (ACEs) in Hispanic children in immigrant families compared with Hispanic children in US-native families. METHODS: Data were from the nationally representative 2011-2012 National Survey of Children's Health. Parent-reported child ACE exposure was classified as no ACEs (0), low ACEs (1), or high ACEs (>=2). By using multinomial logistic regression, we evaluated the odds of low or high ACE exposure versus no ACE exposure by immigrant family status and child and family characteristics (eg, insurance status, child health status, or household-to-income ratio). RESULTS: The study sample included 12 162 Hispanic children. More children in immigrant families lived <=200% of the federal poverty level compared with children in US native families (80% vs 47%, respectively; P < .001). Thirty percent of children in US-native families reported high ACEs compared with only 16% of children in immigrant families (P < .001). The odds of high ACE exposure versus no ACE exposure for children in immigrant families compared with US-native children was 0.46 (95% confidence interval: 0.34-0.61). Child and family characteristics did not explain the difference in odds of ACE exposure by immigrant family status. CONCLUSIONS: Children in immigrant families had significantly lower odds of ACE exposure despite higher prevalence of poverty. This may not reflect a true health advantage in this population. There may be unmeasured factors that buffer children in immigrant families from ACE exposure, or ACE questions may not capture the adverse experiences specific to immigrant families. PMID- 28993446 TI - A Dream Deferred: Ending DACA Threatens Children, Families, and Communities. PMID- 28993447 TI - Background Dietary Patterns and the Time Course of the Blood Pressure Response to Low Sodium Intake. PMID- 28993448 TI - Aberrant Splicing Induced by Dysregulated Rbfox2 Produces Enhanced Function of CaV1.2 Calcium Channel and Vascular Myogenic Tone in Hypertension. AB - Calcium influx from activated voltage-gated calcium channel CaV1.2 in vascular smooth muscle cells is indispensable for maintaining myogenic tone and blood pressure. The function of CaV1.2 channel can be optimized by alternative splicing, one of post-transcriptional modification mechanisms. The splicing factor Rbfox2 is known to regulate the CaV1.2 pre-mRNA alternative splicing events during neuronal development. However, Rbfox2's roles in modulating the key function of vascular CaV1.2 channel and in the pathogenesis of hypertension remain elusive. Here, we report that the proportion of CaV1.2 channels with alternative exon 9* is increased by 10.3%, whereas that with alternative exon 33 is decreased by 10.5% in hypertensive arteries. Surprisingly, the expression level of Rbfox2 is increased ~3-folds, presumably because of the upregulation of a dominant-negative isoform of Rbfox2. In vascular smooth muscle cells, we find that knockdown of Rbfox2 dynamically increases alternative exon 9*, whereas decreases exon 33 inclusion of CaV1.2 channels. By patch-clamp studies, we show that diminished Rbfox2-induced alternative splicing shifts the steady-state activation and inactivation curves of vascular CaV1.2 calcium channel to hyperpolarization, which makes the window current potential to more negative. Moreover, siRNA-mediated knockdown of Rbfox2 increases the pressure-induced vascular myogenic tone of rat mesenteric artery. Taken together, our data indicate that Rbfox2 modulates the functions of vascular CaV1.2 calcium channel by dynamically regulating the expressions of alternative exons 9* and 33, which in turn affects the vascular myogenic tone. Therefore, our work suggests a key role for Rbfox2 in hypertension, which provides a rational basis for designing antihypertensive therapies. PMID- 28993449 TI - Visit-to-Visit Blood Pressure Variability in Young Adulthood and Hippocampal Volume and Integrity at Middle Age: The CARDIA Study (Coronary Artery Risk Development in Young Adults). AB - The aims of this study are to assess the relationships of visit-to-visit blood pressure (BP) variability in young adulthood to hippocampal volume and integrity at middle age. We used data over 8 examinations spanning 25 years collected in the CARDIA study (Coronary Artery Risk Development in Young Adults) of black and white adults (age, 18-30 years) started in 1985 to 1986. Visit-to-visit BP variability was defined as by SDBP and average real variability (ARVBP, defined as the absolute differences of BP between successive BP measurements). Hippocampal tissue volume standardized by intracranial volume (%) and integrity assessed by fractional anisotropy were measured by 3-Tesla magnetic resonance imaging at the year-25 examination (n=545; mean age, 51 years; 54% women and 34% African Americans). Mean systolic BP (SBP)/diastolic BP levels were 110/69 mm Hg at year 0 (baseline), 117/73 mm Hg at year 25, and ARVSBP and SDSBP were 7.7 and 7.9 mm Hg, respectively. In multivariable-adjusted linear models, higher ARVSBP was associated with lower hippocampal volume (unstandardized regression coefficient [standard error] with 1-SD higher ARVSBP: -0.006 [0.003]), and higher SDSBP with lower hippocampal fractional anisotropy (-0.02 [0.01]; all P<0.05), independent of cumulative exposure to SBP during follow-up. Conversely, cumulative exposure to SBP and diastolic BP was not associated with hippocampal volume. There was no interaction by sex or race between ARVSBP or SDSBP with hippocampal volume or integrity. In conclusion, visit-to-visit BP variability during young adulthood may be useful in assessing the potential risk for reductions in hippocampal volume and integrity in midlife. PMID- 28993450 TI - Blood Pressure Genetic Risk Score Predicts Blood Pressure Responses to Dietary Sodium and Potassium: The GenSalt Study (Genetic Epidemiology Network of Salt Sensitivity). AB - We examined the association between genetic risk score (GRS) for blood pressure (BP), based on single nucleotide polymorphisms identified in previous BP genome wide association study meta-analyses, and salt and potassium sensitivity of BP among participants of the GenSalt study (Genetic Epidemiology Network of Salt Sensitivity). The GenSalt study was conducted among 1906 participants who underwent a 7-day low-sodium (51.3 mmol sodium/d), 7-day high-sodium (307.8 mmol sodium/d), and 7-day high-sodium plus potassium (60 mmol potassium/d) intervention. BP was measured 9* at baseline and at the end of each intervention period using a random zero sphygmomanometer. Associations between systolic BP (SBP), diastolic BP, and mean arterial pressure GRS and respective SBP, diastolic BP, and mean arterial pressure responses to the dietary interventions were assessed using mixed linear regression models that accounted for familial dependencies and adjusted for age, sex, field center, body mass index, and baseline BP. As expected, baseline SBP, diastolic BP, and mean arterial pressure significantly increased per quartile increase in GRS (P=2.7*10-8, 9.8*10-8, and 6.4*10-6, respectively). In contrast, increasing GRS quartile conferred smaller SBP, diastolic BP, and mean arterial pressure responses to the low-sodium intervention (P=1.4*10-3, 0.02, and 0.06, respectively) and smaller SBP responses to the high-sodium and potassium interventions (P=0.10 and 0.05). In addition, overall findings were similar when examining GRS as a continuous measure. Contrary to our initial hypothesis, we identified an inverse relationship between BP GRS and salt and potassium sensitivity of BP. These data may provide novel implications on the relationship between BP responses to dietary sodium and potassium and hypertension. PMID- 28993452 TI - Macrolides Blunt Aldosterone Biosynthesis: A Proof-of-Concept Study in KCNJ5 Mutated Adenoma Cells Ex Vivo. AB - Aldosterone-producing adenoma (APA), a major subtype of primary hyperaldosteronism, the main curable cause of human endocrine hypertension, involves somatic mutations in the potassium channel Kir3.4 (KCNJ5) in 30% to 70% of cases, typically the more florid phenotypes. Because KCNJ5 mutated channels were reported to be specifically sensitive to inhibition by macrolide antibiotics, which concentration dependently blunts aldosterone production in HAC15 transfected with the G151R and L168R mutated channel, we herein tested the effect of clarithromycin on aldosterone synthesis and secretion in a pure population of aldosterone-secreting cells obtained by immunoseparation (CD56+ cells) from APA tissues with/without the 2 most common KCNJ5 mutations. From a large cohort of patients with an unambiguous APA diagnosis, we recruited those who were wild type (n=3) or had G151R (n=2) and L168R (n=2) mutations. We found that clarithromycin concentration dependently lowered CYP11B2 gene expression (by 60%) and aldosterone secretion (by 70%; P<0.001 for both) in CD56+ cells isolated ex vivo from KCNJ5 mutated APAs, although it was ineffective in CD56+ cells from wild-type APAs. By proving the principle that the oversecretion of aldosterone can be specifically blunted in APA cells ex vivo with G151R and L168R mutations, these results provide compelling evidence of the possibility of specifically correcting aldosterone excess in patients with APA carrying the 2 most common KCNJ5 somatic mutations. PMID- 28993453 TI - Antidiabetic therapies and male reproductive function: where do we stand? AB - Diabetes mellitus has been increasing at alarming rates in recent years, thus jeopardizing human health worldwide. Several antidiabetic drugs have been introduced in the market to manage glycemic levels, and proven effective in avoiding, minimizing or preventing the appearance or development of diabetes mellitus-related complications. However, and despite the established association between such pathology and male reproductive dysfunction, the influence of these therapeutic interventions on such topics have been scarcely explored. Importantly, this pathology may contribute toward the global decline in male fertility, giving the increasing preponderance of diabetes mellitus in young men at their reproductive age. Therefore, it is mandatory that the reproductive health of diabetic individuals is maintained during the antidiabetic treatment. With this in mind, we have gathered the available information and made a critical analysis regarding the effects of several antidiabetic drugs on male reproductive function. Unlike insulin, which has a clear and fundamental role on male reproductive function, the other antidiabetic therapies' effects at this level seem incoherent. In fact, studies are highly controversial possibly due to the different experimental study approaches, which, in our opinion, suggests caution when it comes to prescribing such drugs to young diabetic patients. Overall, much is still to be determined and further studies are needed to clarify the safety of these antidiabetic strategies on male reproductive system. Aspects such as the effects of insulin levels variations, consequent of insulin therapy, as well as what will be the impact of the side effect hypoglycemia, common to several therapeutic strategies discussed, on the male reproductive system are still to be addressed. PMID- 28993451 TI - Time Course of Change in Blood Pressure From Sodium Reduction and the DASH Diet. AB - : Both sodium reduction and the Dietary Approaches to Stop Hypertension (DASH) diet lower blood pressure (BP); however, the patterns of their effects on BP over time are unknown. In the DASH-Sodium trial, adults with pre-/stage 1 hypertension, not using antihypertensive medications, were randomly assigned to either a typical American diet (control) or DASH. Within their assigned diet, participants randomly ate each of 3 sodium levels (50, 100, and 150 mmol/d, at 2100 kcal) over 4-week periods. BP was measured weekly for 12 weeks; 412 participants enrolled (57% women; 57% black; mean age, 48 years; mean systolic BP [SBP]/diastolic BP [DBP], 135/86 mm Hg). For those assigned control, there was no change in SBP/DBP between weeks 1 and 4 on the high-sodium diet (weekly change, 0.04/0.06 mm Hg/week) versus a progressive decline in BP on the low-sodium diet ( 0.94/-0.70 mm Hg/week; P interactions between time and sodium <0.001 for SBP and DBP). For those assigned DASH, SBP/DBP changed -0.60/-0.16 mm Hg/week on the high versus -0.42/-0.54 mm Hg/week on the low-sodium diet (P interactions between time and sodium=0.56 for SBP and 0.10 for DBP). When comparing DASH to control, DASH changed SBP/DBP by -4.36/-1.07 mm Hg after 1 week, which accounted for most of the effect observed, with no significant difference in weekly rates of change for either SBP (P interaction=0.97) or DBP (P interaction=0.70). In the context of a typical American diet, a low-sodium diet reduced BP without plateau, suggesting that the full effects of sodium reduction are not completely achieved by 4 weeks. In contrast, compared with control, DASH lowers BP within a week without further effect thereafter. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000608. PMID- 28993454 TI - Dynamics of cytoplasm and cleavage divisions correlates with preimplantation embryo development. AB - In vitro fertilization has become increasingly popular as an infertility treatment. In order to improve efficiency of this procedure, there is a strong need for a refinement of existing embryo assessment methods and development of novel, robust and non-invasive selection protocols. Studies conducted on animal models can be extremely helpful here, as they allow for more extensive research on the potential biomarkers of embryo quality. In the present paper, we subjected mouse embryos to non-invasive time-lapse imaging and combined the Particle Image Velocimetry analysis of cytoplasmic dynamics in freshly fertilized oocytes with the morphokinetic analysis of recordings covering 5 days of preimplantation development. Our results indicate that parameters describing cytoplasmic dynamics and cleavage divisions independently correspond to mouse embryo's capacity to form a high-quality blastocyst. We also showed for the first time that these parameters are associated with the percentage of abnormal embryonic cells with fragmented nuclei and with embryo's ability to form primitive endoderm, one of the cell lineages differentiated during preimplantation development. Finally, we present a model that links selected cytoplasmic and morphokinetic parameters reflecting frequency of fertilization-induced Ca2+-oscillations and timing of 4 cell stage and compaction with viability of the embryo assessed as the total number of cells at the end of its preimplantation development. Our results indicate that a combined analysis of cytoplasmic dynamics and morphokinetics may facilitate the assessment of embryo's ability to form high-quality blastocysts. PMID- 28993455 TI - Ehrlichia Activation of Wnt-PI3K-mTOR Signaling Inhibits Autolysosome Generation and Autophagic Destruction by the Mononuclear Phagocyte. AB - In multicellular organisms, autophagy is induced as an innate defense mechanism. Notably, the obligate intracellular bacterium Ehrlichia chaffeensis resides in early endosome-like vacuoles and circumvents lysosomal fusion through an unknown mechanism, thereby avoiding destruction in the autophagolysosome. In this report, we reveal that Wnt signaling plays a crucial role in inhibition of lysosomal fusion and autolysosomal destruction of ehrlichiae. During early infection, autophagosomes fuse with ehrlichial vacuoles to form an amphisome indicated by the presence of autophagy markers such as LC3 (microtubule-associated protein 1 light chain 3), Beclin-1, and p62. LC3 colocalized with ehrlichial morulae on days 1, 2, and 3 postinfection, and increased LC3II levels were detected during infection, reaching a maximal level on day 3. Ehrlichial vacuoles did not colocalize with the lysosomal marker LAMP2, and lysosomes were redistributed and dramatically reduced in level in the infected cells. An inhibitor specific for the Wnt receptor signaling component Dishevelled induced lysosomal fusion with ehrlichial inclusions corresponding to p62 degradation and promoted transcription factor EB (TFEB) nuclear localization. E. chaffeensis infection activated the phosphatidylinositol 3-kinase (PI3K)-Akt-mTOR (mechanistic target of rapamycin) pathway, and activation was induced by three ehrlichial tandem repeat protein (TRP) effectors, with TRP120 inducing the strongest activation. Moreover, induction of glycogen synthase kinase-3 (GSK3) performed using a Wnt inhibitor and small interfering RNA (siRNA) knockdown of critical components of PI3K-GSK3 mTOR signaling decreased ehrlichial survival. This report reveals Ehrlichia exploitation of the evolutionarily conserved Wnt pathway to inhibit autolysosome generation, thereby leading to evasion of this important innate immune defense mechanism. PMID- 28993456 TI - Phosphatidylinositol 4,5-Bisphosphate-Dependent Oligomerization of the Pseudomonas aeruginosa Cytotoxin ExoU. AB - The Pseudomonas aeruginosa type III secretion system delivers effector proteins directly into target cells, allowing the bacterium to modulate host cell functions. ExoU is the most cytotoxic of the known effector proteins and has been associated with more severe infections in humans. ExoU is a patatin-like A2 phospholipase requiring the cellular host factors phosphatidylinositol 4,5 bisphosphate [PI(4,5)P2] and ubiquitin for its activation in vitro We demonstrated that PI(4,5)P2 also induces the oligomerization of ExoU and that this PI(4,5)P2-mediated oligomerization does not require ubiquitin. Single amino acid substitutions in the C-terminal membrane localization domain of ExoU reduced both its activity and its ability to form higher-order complexes in transfected cells and in vitro Combining inactive truncated ExoU proteins partially restored phospholipase activity and cytotoxicity, indicating that ExoU oligomerization may have functional significance. Our results indicate that PI(4,5)P2 induces the oligomerization of ExoU, which may be a mechanism by which this coactivator enhances the phospholipase activity of ExoU. PMID- 28993457 TI - The Electron Transport Chain Sensitizes Staphylococcus aureus and Enterococcus faecalis to the Oxidative Burst. AB - Small-colony variants (SCVs) of Staphylococcus aureus typically lack a functional electron transport chain and cannot produce virulence factors such as leukocidins, hemolysins, or the antioxidant staphyloxanthin. Despite this, SCVs are associated with persistent infections of the bloodstream, bones, and prosthetic devices. The survival of SCVs in the host has been ascribed to intracellular residency, biofilm formation, and resistance to antibiotics. However, the ability of SCVs to resist host defenses is largely uncharacterized. To address this, we measured the survival of wild-type and SCV S. aureus in whole human blood, which contains high numbers of neutrophils, the key defense against staphylococcal infection. Despite the loss of leukocidin production and staphyloxanthin biosynthesis, SCVs defective for heme or menaquinone biosynthesis were significantly more resistant to the oxidative burst than wild-type bacteria in human blood or the presence of purified neutrophils. Supplementation of the culture medium of the heme-auxotrophic SCV with heme, but not iron, restored growth, hemolysin and staphyloxanthin production, and sensitivity to the oxidative burst. Since Enterococcus faecalis is a natural heme auxotroph and cause of bloodstream infection, we explored whether restoration of the electron transport chain in this organism also affected survival in blood. Incubation of E. faecalis with heme increased growth and restored catalase activity but resulted in decreased survival in human blood via increased sensitivity to the oxidative burst. Therefore, the lack of functional electron transport chains in SCV S. aureus and wild-type E. faecalis results in reduced growth rate but provides resistance to a key immune defense mechanism. PMID- 28993458 TI - Dairy Heifers Naturally Exposed to Fasciola hepatica Develop a Type 2 Immune Response and Concomitant Suppression of Leukocyte Proliferation. AB - Fasciola hepatica is a parasitic trematode of global importance in livestock. Control strategies reliant on anthelmintics are unsustainable due to the emergence of drug resistance. Vaccines are under development, but efficacies are variable. Evidence from experimental infection suggests that vaccine efficacy may be affected by parasite-induced immunomodulation. Little is known about the immune response to F. hepatica following natural exposure. Hence, we analyzed the immune responses over time in calves naturally exposed to F. hepatica infection. Cohorts of replacement dairy heifer calves (n = 42) with no prior exposure to F. hepatica, on three commercial dairy farms, were sampled over the course of a grazing season. Exposure was determined through an F. hepatica-specific serum antibody enzyme-linked immunosorbent assay (ELISA) and fluke egg counts. Concurrent changes in peripheral blood leukocyte subpopulations, lymphocyte proliferation, and cytokine responses were measured. Relationships between fluke infection and immune responses were analyzed by using multivariable linear mixed effect models. All calves from one farm showed evidence of exposure, while cohorts from the remaining two farms remained negative over the grazing season. A type 2 immune response was associated with exposure, with increased interleukin-4 (IL-4) production, IL-5 transcription, and eosinophilia. Suppression of parasite specific peripheral blood mononuclear cell (PBMC) proliferation was evident, while decreased mitogen-stimulated gamma interferon (IFN-gamma) production suggested immunomodulation, which was not restricted to parasite-specific responses. Our findings show that the global immune response is modulated toward a nonproliferative type 2 state following natural challenge with F. hepatica This has implications in terms of the timing of the administration of vaccination programs and for host susceptibility to coinfecting pathogens. PMID- 28993459 TI - Acquired Protective Immunity in Atlantic Salmon Salmo salar against the Myxozoan Kudoa thyrsites Involves Induction of MHIIbeta+ CD83+ Antigen-Presenting Cells. AB - The histozoic myxozoan parasite Kudoa thyrsites causes postmortem myoliquefaction and is responsible for economic losses to salmon aquaculture in the Pacific Northwest. Despite its importance, little is known about the host-parasite relationship, including the host response to infection. The present work sought to characterize the immune response in Atlantic salmon during infection, recovery, and reexposure to K. thyrsites After exposure to infective seawater, infected and uninfected smolts were sampled three times over 4,275 degree-days. Histological analysis revealed infection severity decreased over time in exposed fish, while in controls there was no evidence of infection. Following a secondary exposure of all fish, severity of infection in the controls was similar to that measured in exposed fish at the first sampling time but was significantly reduced in reexposed fish, suggesting the acquisition of protective immunity. Using immunohistochemistry, we detected a population of MHIIbeta+ cells in infected muscle that followed a pattern of abundance concordant with parasite prevalence. Infiltration of these cells into infected myocytes preceded destruction of the plasmodium and dissemination of myxospores. Dual labeling indicated a majority of these cells were CD83+/MHIIbeta+ Using reverse transcription-quantitative PCR, we detected significant induction of cellular effectors, including macrophage/dendritic cells (mhii/cd83/mcsf), B cells (igm/igt), and cytotoxic T cells (cd8/nkl), in the musculature of infected fish. These data support a role for cellular effectors such as antigen-presenting cells (monocyte/macrophage and dendritic cells) along with B and T cells in the acquired protective immune response of Atlantic salmon against K. thyrsites. PMID- 28993460 TI - Evaluation of a Plasmodium-Specific Carrier Protein To Enhance Production of Recombinant Pfs25, a Leading Transmission-Blocking Vaccine Candidate. AB - Challenges with the production and suboptimal immunogenicity of malaria vaccine candidates have slowed the development of a Plasmodium falciparum multiantigen vaccine. Attempting to resolve these issues, we focused on the use of highly immunogenic merozoite surface protein 8 (MSP8) as a vaccine carrier protein. Previously, we showed that a genetic fusion of the C-terminal 19-kDa fragment of merozoite surface protein 1 (MSP119) to P. falciparum MSP8 (PfMSP8) facilitated antigen production and folding and the induction of neutralizing antibodies to conformational B cell epitopes of MSP119 Here, using the PfMSP1/8 construct, we further optimized the recombinant PfMSP8 (rPfMSP8) carrier by the introduction of two cysteine-to-serine substitutions (CDeltaS) to improve the yield of the monomeric product. We then sought to test the broad applicability of this approach using the transmission-blocking vaccine candidate Pfs25. The production of rPfs25-based vaccines has presented challenges. Antibodies directed against the four highly constrained epidermal growth factor (EGF)-like domains of Pfs25 block sexual-stage development in mosquitoes. The sequence encoding mature Pfs25 was codon harmonized for expression in Escherichia coli We produced a rPfs25 PfMSP8 fusion protein [rPfs25/8(CDeltaS)] as well as unfused, mature rPfs25. rPfs25 was purified with a modest yield but required the incorporation of refolding protocols to obtain a proper conformation. In comparison, chimeric rPfs25/8(CDeltaS) was expressed and easily purified, with the Pfs25 domain bearing the proper conformation without renaturation. Both antigens were immunogenic in rabbits, inducing IgG that bound native Pfs25 and exhibited potent transmission-reducing activity. These data further demonstrate the utility of PfMSP8 as a parasite-specific carrier protein to enhance the production of complex malaria vaccine targets. PMID- 28993461 TI - Brucella abortus Promotes a Fibrotic Phenotype in Hepatic Stellate Cells, with Concomitant Activation of the Autophagy Pathway. AB - The liver is frequently affected in patients with active brucellosis. The present study demonstrates that Brucella abortus infection induces the activation of the autophagic pathway in hepatic stellate cells to create a microenvironment that promotes a profibrogenic phenotype through the induction of transforming growth factor-beta1 (TGF-beta1), collagen deposition, and inhibition of matrix metalloproteinase-9 (MMP-9) secretion. Autophagy was revealed by upregulation of the LC3II/LC3I ratio and Beclin-1 expression as well as inhibition of p62 expression in infected cells. The above-described findings were dependent on the type IV secretion system (VirB) and the secreted BPE005 protein, which were partially corroborated using the pharmacological inhibitors wortmannin, a phosphatidyl inositol 3-kinase inhibitor, and leupeptin plus E64 (inhibitors of lysosomal proteases). Activation of the autophagic pathway in hepatic stellate cells during Brucella infection could have an important contribution to attenuating inflammatory hepatic injury by inducing fibrosis. However, with time, B. abortus infection induced Beclin-1 cleavage with concomitant cleavage of caspase-3, indicating the onset of apoptosis of LX-2 cells, as was confirmed by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay and Hoechst staining. These results demonstrate that the cross talk of LX-2 cells and B. abortus induces autophagy and fibrosis with concomitant apoptosis of LX-2 cells, which may explain some potential mechanisms of liver damage observed in human brucellosis. PMID- 28993462 TI - A functional analysis of TOEFAZ1 uncovers protein domains essential for cytokinesis in Trypanosoma brucei. AB - The parasite Trypanosoma brucei is highly polarized, including a flagellum that is attached along the cell surface by the flagellum attachment zone (FAZ). During cell division, the new FAZ positions the cleavage furrow, which ingresses from the anterior tip of the cell towards the posterior. We recently identified TOEFAZ1 (for 'Tip of the Extending FAZ protein 1') as an essential protein in trypanosome cytokinesis. Here, we analyzed the localization and function of TOEFAZ1 domains by performing overexpression and RNAi complementation experiments. TOEFAZ1 comprises three domains with separable functions: an N terminal alpha-helical domain that may be involved in FAZ recruitment, a central intrinsically disordered domain that keeps the morphogenic kinase TbPLK at the new FAZ tip, and a C-terminal zinc finger domain necessary for TOEFAZ1 oligomerization. Both the N-terminal and C-terminal domains are essential for TOEFAZ1 function, but TbPLK retention at the FAZ is not necessary for cytokinesis. The feasibility of alternative cytokinetic pathways that do not employ TOEFAZ1 are also assessed. Our results show that TOEFAZ1 is a multimeric scaffold for recruiting proteins that control the timing and location of cleavage furrow ingression. PMID- 28993463 TI - Pib2 and the EGO complex are both required for activation of TORC1. AB - The TORC1 complex is a key regulator of cell growth and metabolism in Saccharomyces cerevisiae The vacuole-associated EGO complex couples activation of TORC1 to the availability of amino acids, specifically glutamine and leucine. The EGO complex is also essential for reactivation of TORC1 following rapamycin induced growth arrest and for its distribution on the vacuolar membrane. Pib2, a FYVE-containing phosphatidylinositol 3-phosphate (PI3P)-binding protein, is a newly discovered and poorly characterized activator of TORC1. Here, we show that Pib2 is required for reactivation of TORC1 following rapamycin-induced growth arrest. Pib2 is required for EGO complex-mediated activation of TORC1 by glutamine and leucine as well as for redistribution of Tor1 on the vacuolar membrane. Therefore, Pib2 and the EGO complex cooperate to activate TORC1 and connect phosphoinositide 3-kinase (PI3K) signaling and TORC1 activity. PMID- 28993464 TI - Lipid-dependent regulation of exocytosis in S. cerevisiae by OSBP homolog (Osh) 4. AB - Polarized exocytosis is an essential process in many organisms and cell types for correct cell division or functional specialization. Previous studies established that homologs of the oxysterol-binding protein (OSBP) in S. cerevisiae, which comprise the Osh protein family, are necessary for efficient polarized exocytosis by supporting a late post-Golgi step. We define this step as the docking of a specific sub-population of exocytic vesicles with the plasma membrane. In the absence of other Osh proteins, yeast Osh4p can support this process in a manner dependent upon two lipid ligands, PI4P and sterol. Osh6p, which binds PI4P and phosphatidylserine, is also sufficient to support polarized exocytosis, again in a lipid-dependent manner. These data suggest that Osh-mediated exocytosis depends upon lipid binding and exchange without a strict requirement for sterol. We propose a two-step mechanism for Osh protein-mediated regulation of polarized exocytosis by using Osh4p as a model. We describe a specific in vivo role for lipid binding by an OSBP-related protein (ORP) in the process of polarized exocytosis, guiding our understanding of where and how OSBP and ORPs may function in more complex organisms. PMID- 28993465 TI - cAMP signaling mediates behavioral flexibility and consolidation of social status in Drosophila aggression. AB - Social rituals, such as male-male aggression in Drosophila, are often stereotyped and the component behavioral patterns modular. The likelihood of transition from one behavioral pattern to another is malleable by experience and confers flexibility to the behavioral repertoire. Experience-dependent modification of innate aggressive behavior in flies alters fighting strategies during fights and establishes dominant-subordinate relationships. Dominance hierarchies resulting from agonistic encounters are consolidated to longer-lasting, social-status dependent behavioral modifications, resulting in a robust loser effect. We showed that cAMP dynamics regulated by the calcium-calmodulin-dependent adenylyl cyclase, Rut, and the cAMP phosphodiesterase, Dnc, but not the Amn gene product, in specific neuronal groups of the mushroom body and central complex, mediate behavioral plasticity necessary to establish dominant-subordinate relationships. rut and dnc mutant flies were unable to alter fighting strategies and establish dominance relationships during agonistic interactions. This real-time flexibility during a fight was independent of changes in aggression levels. Longer-term consolidation of social status in the form of a loser effect, however, required additional Amn-dependent inputs to cAMP signaling and involved a circuit-level association between the alpha/beta and gamma neurons of the mushroom body. Our findings implicate cAMP signaling in mediating the plasticity of behavioral patterns in aggressive behavior and in the generation of a temporally stable memory trace that manifests as a loser effect. PMID- 28993466 TI - Erratum: Deletion of Men1 and somatostatin induces hypergastrinemia and gastric carcinoids. PMID- 28993468 TI - A Ragulator-BORC interaction controls lysosome positioning in response to amino acid availability. AB - Lysosomes play key roles in the cellular response to amino acid availability. Depletion of amino acids from the medium turns off a signaling pathway involving the Ragulator complex and the Rag guanosine triphosphatases (GTPases), causing release of the inactive mammalian target of rapamycin complex 1 (mTORC1) serine/threonine kinase from the lysosomal membrane. Decreased phosphorylation of mTORC1 substrates inhibits protein synthesis while activating autophagy. Amino acid depletion also causes clustering of lysosomes in the juxtanuclear area of the cell, but the mechanisms responsible for this phenomenon are poorly understood. Herein we show that Ragulator directly interacts with BLOC-1-related complex (BORC), a multi-subunit complex previously found to promote lysosome dispersal through coupling to the small GTPase Arl8 and the kinesins KIF1B and KIF5B. Interaction with Ragulator exerts a negative regulatory effect on BORC that is independent of mTORC1 activity. Amino acid depletion strengthens this interaction, explaining the redistribution of lysosomes to the juxtanuclear area. These findings thus demonstrate that amino acid availability controls lysosome positioning through Ragulator-dependent, but mTORC1-independent, modulation of BORC. PMID- 28993470 TI - Fluoride exposure and indicators of thyroid functioning: study design and data analysis considerations. PMID- 28993467 TI - LAMTOR/Ragulator is a negative regulator of Arl8b- and BORC-dependent late endosomal positioning. AB - Signaling from lysosomes controls cellular clearance and energy metabolism. Lysosomal malfunction has been implicated in several pathologies, including neurodegeneration, cancer, infection, immunodeficiency, and obesity. Interestingly, many functions are dependent on the organelle position. Lysosomal motility requires the integration of extracellular and intracellular signals that converge on a competition between motor proteins that ultimately control lysosomal movement on microtubules. Here, we identify a novel upstream control mechanism of Arl8b-dependent lysosomal movement toward the periphery of the cell. We show that the C-terminal domain of lyspersin, a subunit of BLOC-1-related complex (BORC), is essential and sufficient for BORC-dependent recruitment of Arl8b to lysosomes. In addition, we establish lyspersin as the linker between BORC and late endosomal/lysosomal adaptor and mitogen activated protein kinase and mechanistic target of rapamycin activator (LAMTOR) complexes and show that epidermal growth factor stimulation decreases LAMTOR/BORC association, thereby promoting BORC- and Arl8b-dependent lysosomal centrifugal transport. PMID- 28993471 TI - Early life socioeconomic determinants of dietary score and pattern trajectories across six waves of the Longitudinal Study of Australian Children. AB - BACKGROUND: Social patterning of dietary-related diseases may partly be explained by population disparities in children's diets. This study aimed to determine which early life socioeconomic factors best predict dietary trajectories across childhood. METHODS: For waves 2-6 of the Baby (B) Cohort (ages 2-3 to 10-11 years) and waves 1-6 of the Kindergarten (K) Cohort (ages 4-5 to 14-15 years) of the Longitudinal Study of Australian Children, we constructed trajectories of dietary scores and of empirically derived dietary patterns. Dietary scores, based on the Australian Dietary Guidelines, summed children's consumption frequencies of seven groups of foods or drinks over the last 24 hours. Dietary patterns at each wave were derived using factor analyses of 12-16 food or drink items. Using multinomial logistic regression analyses, we examined associations of baseline single (parental education, remoteness area, parental employment, income, food security and home ownership) and composite (socioeconomic position and neighbourhood disadvantage) factors with adherence to dietary trajectories. RESULTS: All dietary trajectory outcomes across both cohorts showed profound gradients by composite socioeconomic position but not by neighbourhood disadvantage. For example, odds for children in the lowest relative to highest socioeconomic position quintile being in the 'never healthy' relative to the 'always healthy' score trajectory were OR=16.40, 95% CI 9.40 to 28.61 (B Cohort). Among the single variables, only parental education consistently predicted dietary trajectories. CONCLUSION: Child dietary trajectories vary profoundly by family socioeconomic position. If causal, reducing dietary inequities may require researching underlying pathways, tackling socioeconomic inequities and targeting health promoting interventions to less educated families. PMID- 28993469 TI - Microtubule stabilization drives 3D centrosome migration to initiate primary ciliogenesis. AB - Primary cilia are sensory organelles located at the cell surface. Their assembly is primed by centrosome migration to the apical surface, yet surprisingly little is known about this initiating step. To gain insight into the mechanisms driving centrosome migration, we exploited the reproducibility of cell architecture on adhesive micropatterns to investigate the cytoskeletal remodeling supporting it. Microtubule network densification and bundling, with the transient formation of an array of cold-stable microtubules, and actin cytoskeleton asymmetrical contraction participate in concert to drive apical centrosome migration. The distal appendage protein Cep164 appears to be a key actor involved in the cytoskeleton remodeling and centrosome migration, whereas intraflagellar transport 88's role seems to be restricted to axoneme elongation. Together, our data elucidate the hitherto unexplored mechanism of centrosome migration and show that it is driven by the increase and clustering of mechanical forces to push the centrosome toward the cell apical pole. PMID- 28993472 TI - Explaining time changes in oral health-related quality of life in England: a decomposition analysis. AB - BACKGROUND: Oral diseases are highly prevalent and impact on oral health-related quality of life (OHRQoL). However, time changes in OHRQoL have been scarcely investigated in the current context of general improvement in clinical oral health. This study aims to examine changes in OHRQoL between 1998 and 2009 among adults in England, and to analyse the contribution of demographics, socioeconomic characteristics and clinical oral health measures. METHODS: Using data from two nationally representative surveys in England, we assessed changes in the Oral Health Impact Profile-14 (OHIP-14), in both the sample overall (n=12 027) and by quasi-cohorts. We calculated the prevalence and extent of oral impacts and summary OHIP-14 scores. An Oaxaca-Blinder type decomposition analysis was used to assess the contribution of demographics (age, gender, marital status), socioeconomic position (education, occupation) and clinical measures (presence of decay, number of missing teeth, having advanced periodontitis). RESULTS: There were significant improvements in OHRQoL, predominantly among those that experienced oral impacts occasionally, but no difference in the proportion with frequent oral impacts. The decomposition model showed that 43% (-4.07/-9.47) of the decrease in prevalence of oral impacts reported occasionally or more often was accounted by the model explanatory variables. Improvements in clinical oral health and the effect of ageing itself accounted for most of the explained change in OHRQoL, but the effect of these factors varied substantially across the lifecourse and quasi-cohorts. CONCLUSIONS: These decomposition findings indicate that broader determinants could be primarily targeted to influence OHRQoL in different age groups or across different adult cohorts. PMID- 28993474 TI - Relapse of neuromyelitis optica associated with oral progestin. PMID- 28993473 TI - Changes in marital quality over 6 years and its association with cardiovascular disease risk factors in men: findings from the ALSPAC prospective cohort study. AB - BACKGROUND: Marital relationship quality has been suggested to have independent effects on cardiovascular health outcomes. This study investigates the association between changes in marital relationship quality and cardiovascular disease (CVD) risk factors in men. METHODS: We used data from The Avon Longitudinal Study of Parents and Children, a prospective birth cohort study (Bristol, UK). Our baseline sample was restricted to married study fathers with baseline relationship and covariate data (n=2496). We restricted final analysis (n=620) to those with complete outcome, exposure and covariate data, who were married and confirmed the study child's father at 6.4 years and 18.8 years after baseline. Relationship quality was measured at baseline and 6.4 years and operationalised as consistently good, improving, deteriorating or consistently poor relationship. We measured CVD risk factors of blood pressure, resting heart rate, body mass index, lipid profile and fasting glucose at 18.8 years after baseline. RESULTS: Improving relationships were associated with lower levels of low-density lipoprotein (-0.25 mmol/L, 95% CI -0.46 to -0.03) and relative reduction of body mass index (-1.07 kg/m2, 95% CI -1.73 to -0.42) compared with consistently good relationships, adjusting for confounders. Weaker associations were found between improving relationships and total cholesterol (-0.24 mmol/L, 95% CI -0.48 to 0.00) and diastolic blood pressure (-2.24 mm Hg, 95% CI -4.59 to +0.11). Deteriorating relationships were associated with worsening diastolic blood pressure (+2.74 mm Hg, 95% CI 0.50 to 4.98). CONCLUSIONS: Improvement and deterioration of longitudinal relationship quality appears associated with respectively positive and negative associations with a range of CVD risk factors. PMID- 28993475 TI - Diet and disease modification in multiple sclerosis: a nutritional epidemiology perspective. PMID- 28993476 TI - Contribution of dietary intake to relapse rate in early paediatric multiple sclerosis. AB - OBJECTIVE: The role of diet in multiple sclerosis (MS) course remains largely unknown. Children with MS have a higher relapse rate compared with MS in adults. Thus, studying the effect of diet on relapse rate in this age group is likely to provide more robust answers. METHODS: This is a multicentre study done at 11 paediatric MS centres in the USA. Patients with relapsing-remitting MS (RRMS) or clinically isolated syndrome (CIS) with disease onset before 18 years of age and duration of less than 4 years were included in this study. Dietary intake during the week before enrolment was assessed with the validated Block Kids Food Screener. The outcome of the study was time from enrolment to the next relapse. 219 patients with paediatric RRMS or CIS were enrolled. Each 10% increase in energy intake from fat increased the hazard of relapse by 56% (adjusted HR 1.56, 95% CI 1.05 to 2.31, p=0.027), and in particular each 10% increase in saturated fat tripled this hazard (adjusted HR: 3.37, 95% CI 1.34 to 8.43, p=0.009). In contrast, each additional one cup equivalent of vegetable decreased the hazard of relapse by 50% (adjusted HR: 0.50, 95% CI 0.27 to 0.91, p=0.024). These associations remained with mutual adjustment and persisted when adjusting for baseline 25(OH) vitamin D serum level. Other studied nutrients were not associated with relapse. CONCLUSIONS: This study suggests that in children with MS, high energy intake from fat, especially saturated fat, may increase the hazard to relapse, while vegetable intake may be independently protective. PMID- 28993477 TI - Development of rapid immunochromatographic strip test for the detection of porcine epidemic diarrhoea virus. AB - Porcine epidemic diarrhoea virus (PEDV) causes acute and severe watery diarrhoea and dehydration, as well as 50-100 per cent mortality in piglets. For the PEDV diagnosis, a rapid test kit that is specific and sensitive to PEDV is critical to monitor this disease at pig farms. The present study aimed to develop an immunochromatographic assay (ICA) strip test for detecting PEDV in faecal swabs. The newly developed diagnostic test showed a detection limit of 104.0 TCID50/ml of PEDV. Using faecal swab samples, the relative sensitivity and specificity of the ICA kit were 95.0 per cent and 98.6 per cent, respectively, compared with those of real-time RT-PCR. In samples from piglets experimentally infected with PEDV, the results showed 100 per cent agreement with those found by real-time RT PCR. Our developed test strip will be useful for rapid diagnosis and can be used for epidemiological surveillance of PEDV infection. PMID- 28993478 TI - Effect of Mutant p53 Proteins on Glycolysis and Mitochondrial Metabolism. AB - TP53 is one of the most commonly mutated genes in human cancers. Unlike other tumor suppressors that are frequently deleted or acquire loss-of-function mutations, the majority of TP53 mutations in tumors are missense substitutions, which lead to the expression of full-length mutant proteins that accumulate in cancer cells and may confer unique gain-of-function (GOF) activities to promote tumorigenic events. Recently, mutant p53 proteins have been shown to mediate metabolic changes as a novel GOF to promote tumor development. There is a strong rationale that the GOF activities, including alterations in cellular metabolism, might vary between the different p53 mutants. Accordingly, the effect of different mutant p53 proteins on cancer cell metabolism is largely unknown. In this study, we have metabolically profiled several individual frequently occurring p53 mutants in cancers, focusing on glycolytic and mitochondrial oxidative phosphorylation pathways. Our investigation highlights the diversity of different p53 mutants in terms of their effect on metabolism, which might provide a foundation for the development of more effective targeted pharmacological approaches toward variants of mutant p53. PMID- 28993479 TI - Lamin B2 Modulates Nucleolar Morphology, Dynamics, and Function. AB - The nucleolus is required for ribosome biogenesis. Human cells have 2 or 3 nucleoli associated with nucleolar organizer region (NOR)-bearing chromosomes. An increase in number and altered nucleolar morphology define cancer cells. However, the mechanisms that modulate nucleolar morphology and function are unclear. Here we show that in addition to localizing at the nuclear envelope, lamin B2 localizes proximal to nucleolin at the granular component (GC) of the nucleolus and associates with the nucleolar proteins nucleolin and nucleophosmin. Lamin B2 knockdown severely disrupted the nucleolar morphology, which was rescued to intact and discrete nucleoli upon lamin B2 overexpression. Furthermore, two mutually exclusive lamin B2 deletion mutants, DeltaHead and DeltaSLS, rescued nuclear and nucleolar morphology defects, respectively, induced upon lamin B2 depletion, suggesting independent roles for lamin B2 at the nucleolus and nuclear envelope. Lamin B2 depletion increased nucleolin aggregation in the nucleoplasm, implicating lamin B2 in stabilizing nucleolin within the nucleolus. Lamin B2 knockdown upregulated nucleolus-specific 45S rRNA and upstream intergenic sequence (IGS) transcripts. The IGS transcripts colocalized with aggregates of nucleolin speckles, which were sustained in the nucleoplasm upon lamin B2 depletion. Taken together, these studies uncover a novel role for lamin B2 in modulating the morphology, dynamics, and function of the nucleolus. PMID- 28993480 TI - Mitochondrial Abnormality Facilitates Cyst Formation in Autosomal Dominant Polycystic Kidney Disease. AB - Autosomal dominant polycystic kidney disease (ADPKD) constitutes the most common inherited kidney disease. Mutations in the PKD1 and PKD2 genes, encoding respective polycystin-1 and polycystin-2 Ca2+ ion channels, results in tubular epithelial cell-derived renal cysts. Recent clinical studies demonstrate oxidative stress as present early in ADPKD. Mitochondria comprise the primary reactive oxygen species source and also their main effector target; however, the pathophysiological role of mitochondria in ADPKD remains uncharacterized. To clarify this function, we examined the mitochondria of cyst-lining cells in ADPKD model mice (Ksp-Cre PKD1flox/flox ) and rats (Han:SPRD Cy/+), demonstrating obvious tubular cell morphological abnormalities. Notably, mitochondrial DNA copy number and peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) expression were decreased in ADPKD model animal kidneys, with PGC 1alpha expression inversely correlated with oxidative stress levels. Consistent with these findings, human ADPKD cyst-derived cells with heterozygous and homozygous PKD1 mutation exhibited morphological and functional abnormalities including increased mitochondrial superoxide. Furthermore, PGC-1alpha expression was suppressed by decreased intracellular Ca2+ levels via calcineurin, p38 mitogen-activated protein kinase (MAPK), and nitric oxide synthase deactivation. Moreover, the mitochondria-specific antioxidant MitoQ reduced intracellular superoxide and inhibited cyst epithelial-cell proliferation through extracellular signal-related kinase/MAPK inactivation. Collectively, these results indicated mitochondrial abnormalities facilitate cyst formation in ADPKD. PMID- 28993482 TI - The Prediction of Impact of a Looming Stimulus onto the Body Is Subserved by Multisensory Integration Mechanisms. AB - In the jungle, survival is highly correlated with the ability to detect and distinguish between an approaching predator and a putative prey. From an ecological perspective, a predator rapidly approaching its prey is a stronger cue for flight than a slowly moving predator. In the present study, we use functional magnetic resonance imaging in the nonhuman primate, to investigate the neural bases of the prediction of an impact to the body by a looming stimulus, i.e., the neural bases of the interaction between a dynamic visual stimulus approaching the body and its expected consequences onto an independent sensory modality, namely, touch. We identify a core cortical network of occipital, parietal, premotor, and prefrontal areas maximally activated by tactile stimulations presented at the predicted time and location of impact of the looming stimulus on the faces compared with the activations observed for spatially or temporally incongruent tactile and dynamic visual cues. These activations reflect both an active integration of visual and tactile information and of spatial and temporal prediction information. The identified cortical network coincides with a well described multisensory visuotactile convergence and integration network suggested to play a key role in the definition of peripersonal space. These observations are discussed in the context of multisensory integration and spatial, temporal prediction and Bayesian causal inference.SIGNIFICANCE STATEMENT Looming stimuli have a particular ecological relevance as they are expected to come into contact with the body, evoking touch or pain sensations and possibly triggering an approach or escape behavior depending on their identity. Here, we identify the nonhuman primate functional network that is maximally activated by tactile stimulations presented at the predicted time and location of impact of the looming stimulus. Our findings suggest that the integration of spatial and temporal predictive cues possibly rely on the same neural mechanisms that are involved in multisensory integration. PMID- 28993481 TI - The mTOR-Bach2 Cascade Controls Cell Cycle and Class Switch Recombination during B Cell Differentiation. AB - The transcription factor Bach2 regulates both acquired and innate immunity at multiple steps, including antibody class switching and regulatory T cell development in activated B and T cells, respectively. However, little is known about the molecular mechanisms of Bach2 regulation in response to signaling of cytokines and antigen. We show here that mammalian target of rapamycin (mTOR) controls Bach2 along B cell differentiation with two distinct mechanisms in pre-B cells. First, mTOR complex 1 (mTORC1) inhibited accumulation of Bach2 protein in nuclei and reduced its stability. Second, mTOR complex 2 (mTORC2) inhibited FoxO1 to reduce Bach2 mRNA expression. Using expression profiling and chromatin immunoprecipitation assay, the Ccnd3 gene, encoding cyclin D3, was identified as a new direct target of Bach2. A proper cell cycle was lost at pre-B and mature B cell stages in Bach2-deficient mice. Furthermore, AZD8055, an mTOR inhibitor, increased class switch recombination in wild-type mature B cells but not in Bach2 deficient cells. These results suggest that the mTOR-Bach2 cascade regulates proper cell cycle arrest in B cells as well as immunoglobulin gene rearrangement. PMID- 28993484 TI - Interneurons in the Honeybee Primary Auditory Center Responding to Waggle Dance Like Vibration Pulses. AB - Female honeybees use the "waggle dance" to communicate the location of nectar sources to their hive mates. Distance information is encoded in the duration of the waggle phase (von Frisch, 1967). During the waggle phase, the dancer produces trains of vibration pulses, which are detected by the follower bees via Johnston's organ located on the antennae. To uncover the neural mechanisms underlying the encoding of distance information in the waggle dance follower, we investigated morphology, physiology, and immunohistochemistry of interneurons arborizing in the primary auditory center of the honeybee (Apis mellifera). We identified major interneuron types, named DL-Int-1, DL-Int-2, and bilateral DL dSEG-LP, that responded with different spiking patterns to vibration pulses applied to the antennae. Experimental and computational analyses suggest that inhibitory connection plays a role in encoding and processing the duration of vibration pulse trains in the primary auditory center of the honeybee.SIGNIFICANCE STATEMENT The waggle dance represents a form of symbolic communication used by honeybees to convey the location of food sources via species-specific sound. The brain mechanisms used to decipher this symbolic information are unknown. We examined interneurons in the honeybee primary auditory center and identified different neuron types with specific properties. The results of our computational analyses suggest that inhibitory connection plays a role in encoding waggle dance signals. Our results are critical for understanding how the honeybee deciphers information from the sound produced by the waggle dance and provide new insights regarding how common neural mechanisms are used by different species to achieve communication. PMID- 28993483 TI - The Ste20 Family Kinases MAP4K4, MINK1, and TNIK Converge to Regulate Stress Induced JNK Signaling in Neurons. AB - The c-Jun-N-terminal kinase (JNK) signaling pathway regulates nervous system development, axon regeneration, and neuronal degeneration after acute injury or in chronic neurodegenerative disease. Dual leucine zipper kinase (DLK) is required for stress-induced JNK signaling in neurons, yet the factors that initiate DLK/JNK pathway activity remain poorly defined. In the present study, we identify the Ste20 kinases MAP4K4, misshapen-like kinase 1 (MINK1 or MAP4K6) and TNIK Traf2- and Nck-interacting kinase (TNIK or MAP4K7), as upstream regulators of DLK/JNK signaling in neurons. Using a trophic factor withdrawal-based model of neurodegeneration in both male and female embryonic mouse dorsal root ganglion neurons, we show that MAP4K4, MINK1, and TNIK act redundantly to regulate DLK activation and downstream JNK-dependent phosphorylation of c-Jun in response to stress. Targeting MAP4K4, MINK1, and TNIK, but not any of these kinases individually, is sufficient to protect neurons potently from degeneration. Pharmacological inhibition of MAP4Ks blocks stabilization and phosphorylation of DLK within axons and subsequent retrograde translocation of the JNK signaling complex to the nucleus. These results position MAP4Ks as important regulators of the DLK/JNK signaling pathway.SIGNIFICANCE STATEMENT Neuronal degeneration occurs in disparate circumstances: during development to refine neuronal connections, after injury to clear damaged neurons, or pathologically during disease. The dual leucine zipper kinase (DLK)/c-Jun-N-terminal kinase (JNK) pathway represents a conserved regulator of neuronal injury signaling that drives both neurodegeneration and axon regeneration, yet little is known about the factors that initiate DLK activity. Here, we uncover a novel role for a subfamily of MAP4 kinases consisting of MAP4K4, Traf2- and Nck-interacting kinase (TNIK or MAP4K7), and misshapen-like kinase 1 (MINK1 or MAP4K6) in regulating DLK/JNK signaling in neurons. Inhibition of these MAP4Ks blocks stress-induced retrograde JNK signaling and protects from neurodegeneration, suggesting that these kinases may represent attractive therapeutic targets. PMID- 28993485 TI - Focusing on the mental health of treatment-seeking veterans. PMID- 28993486 TI - Defence policy and doctrine on captured persons (CPers): further guidance. PMID- 28993487 TI - Managing post laparotomy pain in a contingency setting: the utility of rectus sheath catheters. PMID- 28993488 TI - Support needs and experiences of family members of wounded, injured or sick UK service personnel. AB - INTRODUCTION: When a service person has been wounded, injured or sick (WIS), family members may provide care during their recovery in an unpaid capacity. This may occur in diverse environments including hospitals, inpatient rehabilitation centres, in the community and at home. METHOD: Thirty-seven family members of WIS personnel were interviewed regarding their support needs, family relationships and use of UK support services. Semistructured, in-depth telephone interviews were used, with data analysis undertaken using a thematic approach. RESULTS: 'Family member involvement' was the main theme under which four subthemes were situated: 'continuity of support', 'proactive signposting and initiating contact', 'psychoeducation and counselling' and 'higher risk groups'. Family members felt they might benefit from direct, consistent and continuous care regardless of the WIS person's injury or engagement type, and whether the WIS person was being treated in a hospital, rehabilitative centre or at home. CONCLUSION: The findings of this study suggest that family members of WIS personnel value proactive, direct and sustained communication from support service providers. We suggest that families of UK service personnel may benefit from family care coordinators, who could provide continuous and consistent care to family members of WIS personnel. PMID- 28993489 TI - Civilian and military doctors' knowledge of tranexamic acid (TXA) use in major trauma: a comparison study. AB - INTRODUCTION: Tranexamic acid (TXA) administration within the recommended time of 3 hours has been demonstrated to improve outcomes following trauma. The aim of this study was to identify potential knowledge gaps in the administration of TXA in order to target further educational training in those doctors responsible for the management of acute trauma. METHODS: 104 military and 852 civilian doctors were invited to complete a four-item web-based questionnaire pertaining to the indications, dose, side effects and evidence base for TXA administration in trauma. Doctors of all grades and surgical specialties including emergency trainees and anaesthetics were surveyed. RESULTS: 65 military and 460 civilian doctors responded with a response rate of 62% and 54%, respectively. Responses were required for every question to allow progression and submission. 93% of military doctors knew the initial dose of TXA compared with 34% of civilian doctors. The Clinical randomisation of an Antifibrinolytic in Significant Haemorrhage (CRASH) 2 trial was known to 91% of military doctors compared with 24% of civilian doctors. The optimal time for delivery of TXA in under 3 hours was correctly identified by 91% of military doctors compared with 10% by civilian doctors. DISCUSSION: Military doctors are more familiar with TXA and its side effect profile. Given the potential impact of TXA on patient outcome and the findings of this study, further education of all doctors is recommended including dose, timing and potential side effects. PMID- 28993490 TI - Two sides of a coin: ecological and chronobiological perspectives of timing in the wild. AB - Most processes within organisms, and most interactions between organisms and their environment, have distinct time profiles. The temporal coordination of such processes is crucial across levels of biological organization, but disciplines differ widely in their approaches to study timing. Such differences are accentuated between ecologists, who are centrally concerned with a holistic view of an organism in relation to its external environment, and chronobiologists, who emphasize internal timekeeping within an organism and the mechanisms of its adjustment to the environment. We argue that ecological and chronobiological perspectives are complementary, and that studies at the intersection will enable both fields to jointly overcome obstacles that currently hinder progress. However, to achieve this integration, we first have to cross some conceptual barriers, clarifying prohibitively inaccessible terminologies. We critically assess main assumptions and concepts in either field, as well as their common interests. Both approaches intersect in their need to understand the extent and regulation of temporal plasticity, and in the concept of 'chronotype', i.e. the characteristic temporal properties of individuals which are the targets of natural and sexual selection. We then highlight promising developments, point out open questions, acknowledge difficulties and propose directions for further integration of ecological and chronobiological perspectives through Wild Clock research.This article is part of the themed issue 'Wild Clocks: integrating chronobiology and ecology to understand timekeeping in free-living animals'. PMID- 28993491 TI - Methods in field chronobiology. AB - Chronobiological research has seen a continuous development of novel approaches and techniques to measure rhythmicity at different levels of biological organization from locomotor activity (e.g. migratory restlessness) to physiology (e.g. temperature and hormone rhythms, and relatively recently also in genes, proteins and metabolites). However, the methodological advancements in this field have been mostly and sometimes exclusively used only in indoor laboratory settings. In parallel, there has been an unprecedented and rapid improvement in our ability to track animals and their behaviour in the wild. However, while the spatial analysis of tracking data is widespread, its temporal aspect is largely unexplored. Here, we review the tools that are available or have potential to record rhythms in the wild animals with emphasis on currently overlooked approaches and monitoring systems. We then demonstrate, in three question-driven case studies, how the integration of traditional and newer approaches can help answer novel chronobiological questions in free-living animals. Finally, we highlight unresolved issues in field chronobiology that may benefit from technological development in the future. As most of the studies in the field are descriptive, the future challenge lies in applying the diverse technologies to experimental set-ups in the wild.This article is part of the themed issue 'Wild clocks: integrating chronobiology and ecology to understand timekeeping in free living animals'. PMID- 28993492 TI - Chronobiology of interspecific interactions in a changing world. AB - Animals should time activities, such as foraging, migration and reproduction, as well as seasonal physiological adaptation, in a way that maximizes fitness. The fitness outcome of such activities depends largely on their interspecific interactions; the temporal overlap with other species determines when they should be active in order to maximize their encounters with food and to minimize their encounters with predators, competitors and parasites. To cope with the constantly changing, but predictable structure of the environment, organisms have evolved internal biological clocks, which are synchronized mainly by light, the most predictable and reliable environmental cue (but which can be masked by other variables), which enable them to anticipate and prepare for predicted changes in the timing of the species they interact with, on top of responding to them directly. Here, we review examples where the internal timing system is used to predict interspecific interactions, and how these interactions affect the internal timing system and activity patterns. We then ask how plastic these mechanisms are, how this plasticity differs between and within species and how this variability in plasticity affects interspecific interactions in a changing world, in which light, the major synchronizer of the biological clock, is no longer a reliable cue owing to the rapidly changing climate, the use of artificial light and urbanization.This article is part of the themed issue 'Wild clocks: integrating chronobiology and ecology to understand timekeeping in free living animals'. PMID- 28993493 TI - Timing as a sexually selected trait: the right mate at the right moment. AB - Sexual selection favours the expression of traits in one sex that attract members of the opposite sex for mating. The nature of sexually selected traits such as vocalization, colour and ornamentation, their fitness benefits as well as their costs have received ample attention in field and laboratory studies. However, sexually selected traits may not always be expressed: coloration and ornaments often follow a seasonal pattern and behaviours may be displayed only at specific times of the day. Despite the widely recognized differences in the daily and seasonal timing of traits and their consequences for reproductive success, the actions of sexual selection on the temporal organization of traits has received only scant attention. Drawing on selected examples from bird and mammal studies, here we summarize the current evidence for the daily and seasonal timing of traits. We highlight that molecular advances in chronobiology have opened exciting new opportunities for identifying the genetic targets that sexual selection may act on to shape the timing of trait expression. Furthermore, known genetic links between daily and seasonal timing mechanisms lead to the hypothesis that selection on one timescale may simultaneously also affect the other. We emphasize that studies on the timing of sexual displays of both males and females from wild populations will be invaluable for understanding the nature of sexual selection and its potential to act on differences within and between the sexes in timing. Molecular approaches will be important for pinpointing genetic components of biological rhythms that are targeted by sexual selection, and to clarify whether these represent core or peripheral components of endogenous clocks. Finally, we call for a renewed integration of the fields of evolution, behavioural ecology and chronobiology to tackle the exciting question of how sexual selection contributes to the evolution of biological clocks.This article is part of the themed issue 'Wild clocks: integrating chronobiology and ecology to understand timekeeping in free-living animals'. PMID- 28993494 TI - Seasonal reproductive tactics: annual timing and the capital-to-income breeder continuum. AB - Tactics of resource use for reproduction are an important feature of life-history strategies. A distinction is made between 'capital' breeders, which finance reproduction using stored energy, and 'income' breeders, which pay for reproduction using concurrent energy intake. In reality, vertebrates use a continuum of capital-to-income tactics, and, for many species, the allocation of capital towards reproduction is a plastic trait. Here, we review how trophic interactions and the timing of life-history events are influenced by tactics of resource use in birds and mammals. We first examine how plasticity in the allocation of capital towards reproduction is linked to phenological flexibility via interactions between endocrine/neuroendocrine control systems and the sensory circuits that detect changes in endogenous state, and environmental cues. We then describe the ecological drivers of reproductive timing in species that vary in the degree to which they finance reproduction using capital. Capital can be used either as a mechanism to facilitate temporal synchrony between energy supply and demand or as a means of lessening the need for synchrony. Within many species, an individual's ability to cope with environmental change may be more tightly linked to plasticity in resource allocation than to absolute position on the capital-to income breeder continuum.This article is part of the themed issue 'Wild clocks: integrating chronobiology and ecology to understand timekeeping in free-living animals'. PMID- 28993495 TI - Sleep research goes wild: new methods and approaches to investigate the ecology, evolution and functions of sleep. AB - Despite being a prominent aspect of animal life, sleep and its functions remain poorly understood. As with any biological process, the functions of sleep can only be fully understood when examined in the ecological context in which they evolved. Owing to technological constraints, until recently, sleep has primarily been examined in the artificial laboratory environment. However, new tools are enabling researchers to study sleep behaviour and neurophysiology in the wild. Here, we summarize the various methods that have enabled sleep researchers to go wild, their strengths and weaknesses, and the discoveries resulting from these first steps outside the laboratory. The initial studies to 'go wild' have revealed a wealth of interindividual variation in sleep, and shown that sleep duration is not even fixed within an individual, but instead varies in response to an assortment of ecological demands. Determining the costs and benefits of this inter- and intraindividual variation in sleep may reveal clues to the functions of sleep. Perhaps the greatest surprise from these initial studies is that the reduction in neurobehavioural performance resulting from sleep loss demonstrated in the laboratory is not an obligatory outcome of reduced sleep in the wild.This article is part of the themed issue 'Wild clocks: integrating chronobiology and ecology to understand timekeeping in free-living animals'. PMID- 28993497 TI - Marine biorhythms: bridging chronobiology and ecology. AB - Marine organisms adapt to complex temporal environments that include daily, tidal, semi-lunar, lunar and seasonal cycles. However, our understanding of marine biological rhythms and their underlying molecular basis is mainly confined to a few model organisms in rather simplistic laboratory settings. Here, we use new empirical data and recent examples of marine biorhythms to highlight how field ecologists and laboratory chronobiologists can complement each other's efforts. First, with continuous tracking of intertidal shorebirds in the field, we reveal individual differences in tidal and circadian foraging rhythms. Second, we demonstrate that shorebird species that spend 8-10 months in tidal environments rarely maintain such tidal or circadian rhythms during breeding, likely because of other, more pertinent, temporally structured, local ecological pressures such as predation or social environment. Finally, we use examples of initial findings from invertebrates (arthropods and polychaete worms) that are being developed as model species to study the molecular bases of lunar-related rhythms. These examples indicate that canonical circadian clock genes (i.e. the homologous clock genes identified in many higher organisms) may not be involved in lunar/tidal phenotypes. Together, our results and the examples we describe emphasize that linking field and laboratory studies is likely to generate a better ecological appreciation of lunar-related rhythms in the wild.This article is part of the themed issue 'Wild clocks: integrating chronobiology and ecology to understand timekeeping in free-living animals'. PMID- 28993496 TI - Timing avian long-distance migration: from internal clock mechanisms to global flights. AB - Migratory birds regularly perform impressive long-distance flights, which are timed relative to the anticipated environmental resources at destination areas that can be several thousand kilometres away. Timely migration requires diverse strategies and adaptations that involve an intricate interplay between internal clock mechanisms and environmental conditions across the annual cycle. Here we review what challenges birds face during long migrations to keep track of time as they exploit geographically distant resources that may vary in availability and predictability, and summarize the clock mechanisms that enable them to succeed. We examine the following challenges: departing in time for spring and autumn migration, in anticipation of future environmental conditions; using clocks on the move, for example for orientation, navigation and stopover; strategies of adhering to, or adjusting, the time programme while fitting their activities into an annual cycle; and keeping pace with a world of rapidly changing environments. We then elaborate these themes by case studies representing long-distance migrating birds with different annual movement patterns and associated adaptations of their circannual programmes. We discuss the current knowledge on how endogenous migration programmes interact with external information across the annual cycle, how components of annual cycle programmes encode topography and range expansions, and how fitness may be affected when mismatches between timing and environmental conditions occur. Lastly, we outline open questions and propose future research directions.This article is part of the themed issue 'Wild clocks: integrating chronobiology and ecology to understand timekeeping in free-living animals'. PMID- 28993499 TI - Time is honey: circadian clocks of bees and flowers and how their interactions may influence ecological communities. AB - The interactions between flowering plants and insect pollinators shape ecological communities and provide one of the best examples of coevolution. Although these interactions have received much attention in both ecology and evolution, their temporal aspects are little explored. Here we review studies on the circadian organization of pollination-related traits in bees and flowers. Research, mostly with the honeybee, Apis mellifera, has implicated the circadian clock in key aspects of their foraging for flower rewards. These include anticipation, timing of visits to flowers at specified locations and time-compensated sun-compass orientation. Floral rhythms in traits such as petal opening, scent release and reward availability also show robust daily rhythms. However, in only few studies was it possible to adequately determine whether these oscillations are driven by external time givers such as light and temperature cycles, or endogenous circadian clocks. The interplay between the timing of flower and pollinator rhythms may be ecologically significant. Circadian regulation of pollination related traits in only few species may influence the entire pollination network and thus affect community structure and local biodiversity. We speculate that these intricate chronobiological interactions may be vulnerable to anthropogenic effects such as the introduction of alien invasive species, pesticides or environmental pollutants.This article is part of the themed issue 'Wild clocks: integrating chronobiology and ecology to understand timekeeping in free-living animals'. PMID- 28993500 TI - Keeping time without a spine: what can the insect clock teach us about seasonal adaptation? AB - Seasonal change in daylength (photoperiod) is widely used by insects to regulate temporal patterns of development and behaviour, including the timing of diapause (dormancy) and migration. Flexibility of the photoperiodic response is critical for rapid shifts to new hosts, survival in the face of global climate change and to reproductive isolation. At the same time, the daily circadian clock is also essential for development, diapause and multiple behaviours, including correct flight orientation during long-distance migration. Although studied for decades, how these two critical biological timing mechanisms are integrated is poorly understood, in part because the core circadian clock genes are all transcription factors or regulators that are able to exert multiple effects throughout the genome. In this chapter, we discuss clocks in the wild from the perspective of diverse insect groups across eco-geographic contexts from the Antarctic to the tropical regions of Earth. Application of the expanding tool box of molecular techniques will lead us to distinguish universal from unique mechanisms underlying the evolution of circadian and photoperiodic timing, and their interaction across taxonomic and ecological contexts represented by insects.This article is part of the themed issue 'Wild clocks: integrating chronobiology and ecology to understand timekeeping in free-living animals'. PMID- 28993498 TI - Flexible clock systems: adjusting the temporal programme. AB - Under natural conditions, many aspects of the abiotic and biotic environment vary with time of day, season or even era, while these conditions are typically kept constant in laboratory settings. The timing information contained within the environment serves as critical timing cues for the internal biological timing system, but how this system drives daily rhythms in behaviour and physiology may also depend on the internal state of the animal. The disparity between timing of these cues in natural and laboratory conditions can result in substantial differences in the scheduling of behaviour and physiology under these conditions. In nature, temporal coordination of biological processes is critical to maximize fitness because they optimize the balance between reproduction, foraging and predation risk. Here we focus on the role of peripheral circadian clocks, and the rhythms that they drive, in enabling adaptive phenotypes. We discuss how reproduction, endocrine activity and metabolism interact with peripheral clocks, and outline the complex phenotypes arising from changes in this system. We conclude that peripheral timing is critical to adaptive plasticity of circadian organization in the field, and that we must abandon standard laboratory conditions to understand the mechanisms that underlie this plasticity which maximizes fitness under natural conditions.This article is part of the themed issue 'Wild clocks: integrating chronobiology and ecology to understand timekeeping in free-living animals'. PMID- 28993501 TI - Wild clocks: preface and glossary. PMID- 28993502 TI - Cardiovascular Effects of Renal Distal Tubule Deletion of the FGF Receptor 1 Gene. AB - The bone-derived hormone fibroblast growth factor-23 (FGF-23) activates complexes composed of FGF receptors (FGFRs), including FGFR1, and alpha-Klotho in the kidney distal tubule (DT), leading to increased sodium retention and hypertension. However, the role of FGFR1 in regulating renal processes linked to hypertension is unclear. Here, we investigated the effects of selective FGFR1 loss in the DT. Conditional knockout (cKO) of FGFR1 in the DT (FGFR1DT-cKO mice) resulted in left ventricular hypertrophy (LVH) and decreased kidney expression of alpha-Klotho in association with enhanced BP, decreased expression of angiotensin converting enzyme 2, and increased expression of the Na+-K+-2Cl- cotransporter. Notably, recombinant FGF-23 administration similarly decreased the kidney expression of alpha-Klotho and induced LVH in mice. Pharmacologic activation of FGFR1 with a monoclonal anti-FGFR1 antibody (R1MAb1) normalized BP and significantly attenuated LVH in the Hyp mouse model of excess FGF-23, but did not induce a response in FGFR1DT-cKO mice. The hearts of FGFR1DT-cKO mice showed increased expression of the transient receptor potential cation channel, subfamily C, member 6 (TRPC6), consistent with cardiac effects of soluble Klotho deficiency. Moreover, administration of recombinant soluble Klotho lowered BP in the Hyp mice. Thus, FGFR1 in the DT regulates systemic hemodynamic responses opposite to those predicted by the actions of FGF-23. These cardiovascular effects appear to be mediated by paracrine FGF control of kidney FGFR1 and subsequent regulation of soluble Klotho and TRPC6. FGFR1 in the kidney may provide a new molecular target for treating hypertension. PMID- 28993503 TI - MYH9 E1841K Mutation Augments Proteinuria and Podocyte Injury and Migration. AB - Intronic variants of the MYH9 gene that encodes the nonmuscle myosin heavy chain IIA are associated with diabetic nephropathy in European Americans and with sickle cell disease-associated nephropathy. However, the causal functional variants of MYH9 have remained elusive. Rare missense mutations in MYH9 cause macrothrombocytopenia and are occasionally associated with development of nephropathy. The E1841K mutation is among the common MYH9 missense mutations and has been associated with nephropathy in some carriers. To determine the contribution of the E1841K mutation in kidney disease, we studied the effects of the E1841K mutation in mice subjected to high salt or angiotensin II (Ang II) as models of hypertension and in mice subjected to renal mass reduction as a model of CKD. Despite similar levels of BP among wild-type (MYH9+/+ ) mice and mice heterozygous (MYH9+/E1841K ) and homozygous (MYH9E1841K/E1841K ) for the mutation in each model, MYH9E1841K/E1841K mice exhibited mildly increased albuminuria in response to high salt; severe albuminuria, nephrinuria, FSGS, and podocyte foot effacement in Ang II-induced hypertension; and early mortality in the renal mass reduction model. Treatment with candesartan during Ang II-induced hypertension attenuated kidney disease development in MYH9E1841K/E1841K mice. In vitro, isolated primary podocytes from MYH9E1841K/E1841K mice exhibited increased lamellipodia formation and reorganization of F-actin stress fibers. Wound healing assays revealed that MYH9+/+ podocytes had the lowest migration rate, followed by MYH9+/E1841K then MYH9E1841K/E1841K podocytes. In conclusion, the MYH9 E1841K variant alters podocyte cytoskeletal structure and renders podocytes more susceptible to injury after a damaging stimulus. PMID- 28993504 TI - Precision Transplant Medicine: Biomarkers to the Rescue. AB - The concept that individuals with the same disease and a similar clinical presentation may have very different outcomes and need very different therapies is not novel. With the development of many innovative tools derived from the omics technologies, transplant medicine is slowly entering the era of precision medicine. Biomarkers are the cornerstone of precision medicine, which aims to integrate biomarkers with traditional clinical information and tailor medical care to achieve the best outcome for an individual patient. Here, we discuss the basic concepts of precision medicine and biomarkers, with a specific focus on progress in renal transplantation. We delineate the different types of biomarkers and provide a general assessment of the current applications and shortcomings of previously proposed biomarkers. We also outline the potential of precision medicine in transplantation. Moving toward precision medicine in the field of transplantation will require transplant physicians to embrace the increased complexity and expanded decision algorithms and therapeutic options that are associated with improved disease nosology. PMID- 28993505 TI - Factor H Competitor Generated by Gene Conversion Events Associates with Atypical Hemolytic Uremic Syndrome. AB - Atypical hemolytic uremic syndrome (aHUS), a rare form of thrombotic microangiopathy caused by complement pathogenic variants, mainly affects the kidney microvasculature. A retrospective genetic analysis in our aHUS cohort (n=513) using multiple ligation probe amplification uncovered nine unrelated patients carrying a genetic abnormality in the complement factor H related 1 gene (CFHR1) that originates by recurrent gene conversion events between the CFH and CFHR1 genes. The novel CFHR1 mutants encode an FHR-1 protein with two amino acid substitutions, L290S and A296V, converting the FHR-1 C terminus into that of factor H (FH). Next-generation massive-parallel DNA sequencing (NGS) analysis did not detect these genetic abnormalities. In addition to the CFHR1 mutant, six patients carried the previously uncharacterized CFH-411T variant. In functional analyses, the mutant FHR-1 protein strongly competed the binding of FH to cell surfaces, impairing complement regulation, whereas the CFH-411T polymorphism lacked functional consequences. Carriers of the CFHR1 mutation presented with severe aHUS during adulthood; 57% of affected women in this cohort presented during the postpartum period. Analyses in patients and unaffected carriers showed that FH plasma levels determined by the nonmutated chromosome modulate disease penetrance. Crucially, in the activated endothelial (HMEC-1) cell assay, reduced FH plasma levels produced by the nonmutated chromosome correlated inversely with impairment of complement regulation, measured as C5b-9 deposition. Our data advance understanding of the genetic complexities underlying aHUS, illustrate the importance of performing functional analysis, and support the use of complementary assays to disclose genetic abnormalities not revealed by current NGS analysis. PMID- 28993506 TI - Kidney Proximal Tubule Lipoapoptosis Is Regulated by Fatty Acid Transporter-2 (FATP2). AB - Albuminuria and tubular atrophy are among the highest risks for CKD progression to ESRD. A parsimonious mechanism involves leakage of albumin-bound nonesterified fatty acids (NEFAs) across the damaged glomerular filtration barrier and subsequent reabsorption by the downstream proximal tubule, causing lipoapoptosis. We sought to identify the apical proximal tubule transporter that mediates NEFA uptake and cytotoxicity. We observed transporter-mediated uptake of fluorescently labeled NEFA in cultured proximal tubule cells and microperfused rat proximal tubules, with greater uptake from the apical surface than from the basolateral surface. Protein and mRNA expression analyses revealed that kidney proximal tubules express transmembrane fatty acid transporter-2 (FATP2), encoded by Slc27a2, but not the other candidate transporters CD36 and free fatty acid receptor 1. Kidney FATP2 localized exclusively to proximal tubule epithelial cells along the apical but not the basolateral membrane. Treatment of mice with lipidated albumin to induce proteinuria caused a decrease in the proportion of tubular epithelial cells and an increase in the proportion of interstitial space in kidneys from wild-type but not Slc27a2-/- mice. Ex vivo microperfusion and in vitro experiments with NEFA-bound albumin at concentrations that mimic apical proximal tubule exposure during glomerular injury revealed significantly reduced NEFA uptake and palmitate-induced apoptosis in microperfused Slc27a2-/- proximal tubules and Slc27a2-/- or FATP2 shRNA-treated proximal tubule cell lines compared with wild-type or scrambled oligonucleotide-treated cells, respectively. We conclude that FATP2 is a major apical proximal tubule NEFA transporter that regulates lipoapoptosis and may be an amenable target for the prevention of CKD progression. PMID- 28993508 TI - Personalized siRNA-Nanoparticle Systemic Therapy using Metastatic Lymph Node Specimens Obtained with EBUS-TBNA in Lung Cancer. AB - Inhibiting specific gene expression with siRNA provides a new therapeutic strategy to tackle many diseases at the molecular level. Recent strategies called high-density lipoprotein (HDL)-mimicking peptide-phospholipid nanoscaffold (HPPS) nanoparticles have been used to induce siRNAs-targeted delivery to scavenger receptor class B type I receptor (SCARB1)-expressing cancer cells with high efficiency. Here, eight ideal therapeutic target genes were identified for advanced lung cancer throughout the screenings using endobronchial ultrasonography-guided transbronchial needle aspiration (EBUS-TBNA) and the establishment of a personalized siRNA-nanoparticle therapy. The relevance of these genes was evaluated by means of siRNA experiments in cancer cell growth. To establish a therapeutic model, kinesin family member-11 (KIF11) was selected as a target gene. A total of 356 lung cancers were analyzed immunohistochemically for its clinicopathologic significance. The antitumor effect of HPPS-conjugated siRNA was evaluated in vivo using xenograft tumor models. Inhibition of gene expression for these targets effectively suppressed lung cancer cell growth. SCARB1 was highly expressed in a subset of tumors from the lung large-cell carcinoma (LCC) and small-cell lung cancer (SCLC) patients. High-level KIF11 expression was identified as an independent prognostic factor in LCC and squamous cell carcinoma (SqCC) patients. Finally, a conjugate of siRNA against KIF11 and HPPS nanoparticles induced downregulation of KIF11 expression and mediated dramatic inhibition of tumor growth in vivoImplications: This approach showed delivering personalized cancer-specific siRNAs via the appropriate nanocarrier may be a novel therapeutic option for patients with advanced lung cancer. Mol Cancer Res; 16(1); 47-57. (c)2017 AACR. PMID- 28993507 TI - Dialysate Potassium, Dialysate Magnesium, and Hemodialysis Risk. AB - One of the fundamental goals of the hemodialysis prescription is to maintain serum potassium levels within a narrow normal range during both the intradialytic and interdialytic intervals. Considering the extraordinarily high rate of cardiovascular mortality in the hemodialysis population, clinicians are obligated to explore whether factors related to dialytic potassium removal can be modified to improve clinical outcomes. Observational studies and circumstantial evidence suggest that extreme concentrations of serum and dialysate potassium can trigger cardiac arrest. In this review, we provide an overview of factors affecting overall potassium balance and factors modulating potassium dialysate fluxes in dialysis, and we review data linking serum and dialysate potassium concentrations with arrhythmias, cardiovascular events, and mortality. We explore potential interactions between serum and dialysate magnesium levels and risks associated with dialysate potassium levels. Finally, we conclude with proposed dialytic and novel nondialytic approaches to optimize outcomes related to potassium homeostasis in patients on hemodialysis. Dialysis clinicians need to consider changes in the overall clinical scenario when choosing dialysate potassium concentrations, and an effective change in practice will require more frequent serum potassium monitoring and responsive dialysis care teams. PMID- 28993509 TI - A Large-Scale RNAi Screen Identifies SGK1 as a Key Survival Kinase for GBM Stem Cells. AB - Glioblastoma multiforme (GBM) is the most common type of primary malignant brain cancer and has a very poor prognosis. A subpopulation of cells known as GBM stem like cells (GBM-SC) have the capacity to initiate and sustain tumor growth and possess molecular characteristics similar to the parental tumor. GBM-SCs are known to be enriched in hypoxic niches and may contribute to therapeutic resistance. Therefore, to identify genetic determinants important for the proliferation and survival of GBM stem cells, an unbiased pooled shRNA screen of 10,000 genes was conducted under normoxic as well as hypoxic conditions. A number of essential genes were identified that are required for GBM-SC growth, under either or both oxygen conditions, in two different GBM-SC lines. Interestingly, only about a third of the essential genes were common to both cell lines. The oxygen environment significantly impacts the cellular genetic dependencies as 30% of the genes required under hypoxia were not required under normoxic conditions. In addition to identifying essential genes already implicated in GBM such as CDK4, KIF11, and RAN, the screen also identified new genes that have not been previously implicated in GBM stem cell biology. The importance of the serum and glucocorticoid-regulated kinase 1 (SGK1) for cellular survival was validated in multiple patient-derived GBM stem cell lines using shRNA, CRISPR, and pharmacologic inhibitors. However, SGK1 depletion and inhibition has little effect on traditional serum grown glioma lines and on differentiated GBM-SCs indicating its specific importance in GBM stem cell survival.Implications: This study identifies genes required for the growth and survival of GBM stem cells under both normoxic and hypoxic conditions and finds SGK1 as a novel potential drug target for GBM. Mol Cancer Res; 16(1); 103-14. (c)2017 AACR. PMID- 28993510 TI - Genomic Gain of 16p13.3 in Prostate Cancer Predicts Poor Clinical Outcome after Surgical Intervention. AB - Identifying tumors with high metastatic potential is key to improving the clinical management of prostate cancer. Recently, we characterized a chromosome 16p13.3 gain frequently observed in prostate cancer metastases and now demonstrate the prognostic value of this genomic alteration in surgically treated prostate cancer. Dual-color FISH was used to detect 16p13.3 gain on a human tissue microarray representing 304 primary radical prostatectomy (RP) cases with clinical follow-up data. The results were validated in an external dataset. The 16p13.3 gain was detected in 42% (113/267) of the specimens scorable by FISH and was significantly associated with clinicopathologic features of aggressive prostate cancer, including high preoperative PSA (P = 0.03) levels, high Gleason score (GS, P < 0.0001), advanced pathologic tumor stage (P < 0.0001), and positive surgical margins (P = 0.009). The 16p13.3 gain predicted biochemical recurrence (BCR) in the overall cohort (log-rank P = 0.0005), and in subsets of patients with PSA <=10 or GS <=7 (log-rank P = 0.02 and P = 0.006, respectively). Moreover, combining the 16p13.3 gain status with standard prognostic markers improved BCR risk stratification and identified a subgroup of patients with high probability of recurrence. The 16p13.3 gain status was also associated with an increased risk of developing distant metastases (log-rank P = 0.03) further substantiating its role in prostate cancer progression.Implications: This study demonstrates the prognostic significance of the 16p13.3 genomic gain in primary prostate tumors, suggesting potential utility in the clinical management of the disease by identifying patients at high risk of recurrence who may benefit from adjuvant therapies. Mol Cancer Res; 16(1); 115-23. (c)2017 AACR. PMID- 28993511 TI - Cell Cycle-Dependent Tumor Engraftment and Migration Are Enabled by Aurora-A. AB - Cell-cycle progression and the acquisition of a migratory phenotype are hallmarks of human carcinoma cells that are perceived as independent processes but may be interconnected by molecular pathways that control microtubule nucleation at centrosomes. Here, cell-cycle progression dramatically impacts the engraftment kinetics of 4T1-luciferase2 breast cancer cells in immunocompetent BALB/c or immunocompromised NOD-SCID gamma (NSG) mice. Multiparameter imaging of wound closure assays was used to track cell-cycle progression, cell migration, and associated phenotypes in epithelial cells or carcinoma cells expressing a fluorescence ubiquitin cell-cycle indicator. Cell migration occurred with an elevated velocity and directionality during the S-G2-phase of the cell cycle, and cells in this phase possess front-polarized centrosomes with augmented microtubule nucleation capacity. Inhibition of Aurora kinase-A (AURKA/Aurora-A) dampens these phenotypes without altering cell-cycle progression. During G2 phase, the level of phosphorylated Aurora-A at centrosomes is reduced in hyaluronan-mediated motility receptor (HMMR)-silenced cells as is the nuclear transport of TPX2, an Aurora-A-activating protein. TPX2 nuclear transport depends upon HMMR-T703, which releases TPX2 from a complex with importin-alpha (KPNA2) at the nuclear envelope. Finally, the abundance of phosphorylated HMMR-T703, a substrate for Aurora-A, predicts breast cancer-specific survival and relapse-free survival in patients with estrogen receptor (ER)-negative (n = 941), triple negative (TNBC) phenotype (n = 538), or basal-like subtype (n = 293) breast cancers, but not in those patients with ER-positive breast cancer (n = 2,218). Together, these data demonstrate an Aurora-A/TPX2/HMMR molecular axis that intersects cell-cycle progression and cell migration.Implications: Tumor cell engraftment, migration, and cell-cycle progression share common regulation of the microtubule cytoskeleton through the Aurora-A/TPX2/HMMR axis, which has the potential to influence the survival of patients with ER-negative breast tumors. Mol Cancer Res; 16(1); 16-31. (c)2017 AACR. PMID- 28993512 TI - Loss of NLRX1 Exacerbates Neural Tissue Damage and NF-kappaB Signaling following Brain Injury. AB - Traumatic and nontraumatic brain injury results from severe disruptions in the cellular microenvironment leading to massive loss of neuronal populations and increased neuroinflammation. The progressive cascade of secondary events, including ischemia, inflammation, excitotoxicity, and free-radical release, contribute to neural tissue damage. NLRX1 is a member of the NLR family of pattern recognition receptors and is a potent negative regulator of several pathways that significantly modulate many of these events. Thus, we hypothesized that NLRX1 limits immune system signaling in the brain following trauma. To evaluate this hypothesis, we used Nlrx1-/- mice in a controlled cortical impact (CCI) injury murine model of traumatic brain injury (TBI). In this article, we show that Nlrx1-/- mice exhibited significantly larger brain lesions and increased motor deficits following CCI injury. Mechanistically, our data indicate that the NF-kappaB signaling cascade is significantly upregulated in Nlrx1-/- animals. This upregulation is associated with increased microglia and macrophage populations in the cortical lesion. Using a mouse neuroblastoma cell line (N2A), we also found that NLRX1 significantly reduced apoptosis under hypoxic conditions. In human patients, we identify 15 NLRs that are significantly dysregulated, including significant downregulation of NLRX1 in brain injury following aneurysm. We further demonstrate a concurrent increase in NF-kappaB signaling that is correlated with aneurysm severity in these human subjects. Together, our data extend the function of NLRX1 beyond its currently characterized role in host-pathogen defense and identify this highly novel NLR as a significant modulator of brain injury progression. PMID- 28993513 TI - DNA Vaccination by Electroporation Amplifies Broadly Cross-Restricted Public TCR Clonotypes Shared with HIV Controllers. AB - Rare patients who spontaneously control HIV replication provide a useful model to inform HIV vaccine development. HIV controllers develop particularly efficient antiviral CD4+ T cell responses mediated by shared high-affinity TCRs. To determine whether the candidate DNA vaccine ADVAX could induce similar responses, we analyzed Gag-specific primary CD4+ T cells from healthy volunteers who received ADVAX DNA by electroporation. Vaccinated volunteers had an immunodominant response to the Gag293 epitope with a functional avidity intermediate between that of controllers and treated patients. The TCR repertoire of Gag293-specific CD4+ T cells proved highly biased, with a predominant usage of the TCRbeta variable gene 2 (TRBV2) in vaccinees as well as controllers. TCRalpha variable gene (TRAV) gene usage was more diverse, with the dominance of TRAV29 over TRAV24 genes in vaccinees, whereas TRAV24 predominated in controllers. Sequence analysis revealed an unexpected degree of overlap between the specific repertoires of vaccinees and controllers, with the sharing of TRAV24 and TRBV2 public motifs (>30%) and of public clonotypes characteristic of high-affinity TCRs. MHC class II tetramer binding revealed a broad HLA-DR cross-restriction, explaining how Gag293-specific public clonotypes could be selected in individuals with diverse genetic backgrounds. TRAV29 clonotypes also proved cross-restricted, but conferred responses of lower functional avidity upon TCR transfer. In conclusion, DNA vaccination by electroporation primed for TCR clonotypes that were associated with HIV control, highlighting the potential of this vaccine delivery method. To our knowledge, this study provides the first proof-of-concept that clonotypic analysis may be used as a tool to monitor the quality of vaccine induced responses and modulate these toward "controller-like" responses. PMID- 28993516 TI - Mechanisms of the Innate Defense Regulator Peptide-1002 Anti-Inflammatory Activity in a Sterile Inflammation Mouse Model. AB - Innate defense regulator (IDR) peptide-1002 is a synthetic host defense peptide derivative with strong anti-inflammatory properties. Extending previous data, IDR 1002 suppressed in vitro inflammatory responses in RAW 264.7 murine monocyte/macrophage cells challenged with the TLR4 agonist LPS and TLR2 agonists lipoteichoic acid and zymosan. To investigate the anti-inflammatory mechanisms of IDR-1002 in vivo, the PMA-induced mouse ear inflammation model was used. Topical IDR-1002 treatment successfully dampened PMA-induced ear edema, proinflammatory cytokine production, reactive oxygen and nitrogen species release, and neutrophil recruitment in the ears of CD1 mice. Advanced RNA transcriptomic analysis on the mouse ear transcriptome revealed that IDR-1002 reduced sterile inflammation by suppressing the expression of transmembrane G protein-coupled receptors (class A/1 rhodopsin-like), including receptors for chemokines, PGs, histamine, platelet activating factor, and anaphylatoxin. IDR-1002 also dampened the IFN-gamma response and repressed the IFN regulatory factor 8-regulated network that controls central inflammatory pathways. This study demonstrates that IDR-1002 exhibits strong in vitro and in vivo anti-inflammatory activities, informs the underlying anti-inflammatory mechanisms, and reveals its potential as a novel therapeutic for inflammatory diseases. PMID- 28993514 TI - The NF-kappaB-Responsive Long Noncoding RNA FIRRE Regulates Posttranscriptional Regulation of Inflammatory Gene Expression through Interacting with hnRNPU. AB - Long noncoding RNAs, a newly identified class of noncoding RNAs, are important regulators of gene expression in innate immunity. We report in this study that the transcription of FIRRE, a conserved long noncoding RNA between humans and mice, is controlled by NF-kappaB signaling in macrophages and intestinal epithelial cells. Functionally, FIRRE appears to positively regulate the expression of several inflammatory genes in macrophages or intestinal epithelial cells in response to LPS stimulation via posttranscriptional mechanisms. Specifically, FIRRE physically interacts with heterogeneous nuclear ribonucleoproteins U, regulating the stability of mRNAs of selected inflammatory genes through targeting the AU-rich elements of their mRNAs in cells following LPS stimulation. Therefore, our data indicate a new regulatory role for NF-kappaB responsive FIRRE in the posttranscriptional regulation of inflammatory genes in the innate immune system. PMID- 28993515 TI - Nonclassical Monocytes Mediate Secondary Injury, Neurocognitive Outcome, and Neutrophil Infiltration after Traumatic Brain Injury. AB - Traumatic brain injury (TBI) results in rapid recruitment of leukocytes into the injured brain. Monocytes constitute a significant proportion of the initial infiltrate and have the potential to propagate secondary brain injury or generate an environment of repair and regeneration. Monocytes are a diverse population of cells (classical, intermediate, and nonclassical) with distinct functions, however, the recruitment order of these subpopulations to the injured brain largely remains unknown. Thus, we examined which monocyte subpopulations are required for the generation of early inflammatory infiltrate within the injured brain, and whether their depletion attenuates secondary injury or neurocognitive outcome. Global monocyte depletion correlated with significant improvements in brain edema, motor coordination, and working memory, and abrogated neutrophil infiltration into the injured brain. However, targeted depletion of classical monocytes alone had no effect on neutrophil recruitment to the site of injury, implicating the nonclassical monocyte in this process. In contrast, mice that have markedly reduced numbers of nonclassical monocytes (CX3CR1-/-) exhibited a significant reduction in neutrophil infiltration into the brain after TBI as compared with control mice. Our data suggest a critical role for nonclassical monocytes in the pathology of TBI in mice, including important clinical outcomes associated with mortality in this injury process. PMID- 28993518 TI - Naringenin Ameliorates Acute Inflammation by Regulating Intracellular Cytokine Degradation. AB - Ungoverned activation of innate and adaptive immunity results in acute inflammatory disease, such as bacteria-induced endotoxemia and fulminant hepatitis by virus infection. Thus, therapeutic control of inflammation is crucial for clinical management of many human diseases. In murine models of LPS- and Con A-induced liver injury, we found that naringenin, a natural predominant flavanone, is capable of protecting against lethality induced by LPS and preventing inflammation-induced organ injury. The protective effect of naringenin is mediated by reducing the levels of several inflammatory cytokines. Unexpectedly, naringenin inhibits TNF-alpha and IL-6 secretion in macrophages and T cells without interfering with the TLR signaling cascade, cytokine mRNA stability, or protein translation. These results indicate the existence of a posttranslational control mechanism. Further studies show that naringenin enhances intracellular cytokine degradation through lysosome- and TFEB-dependent mechanisms. This study provides evidence that naringenin has the capacity to dampen cytokine production by regulating lysosome function. Thus, naringenin may represent a potential therapeutic agent for controlling inflammation-related diseases. PMID- 28993517 TI - Revisiting the Road Map of Medullary Thymic Epithelial Cell Differentiation. AB - The basic two-step terminal differentiation model of the medullary thymic epithelial cell (mTEC) lineage from immature MHC class II (MHCII)lo to mature MHCIIhi mTECs has recently been extended to include a third stage, namely the post-Aire MHCIIlo subset as identified by lineage-tracing models. However, a suitable surface marker distinguishing the phenotypically overlapping pre- from the post-Aire MHCIIlo stage has been lacking. In this study, we introduce the lectin Tetragonolobus purpureas agglutinin (TPA) as a novel cell surface marker that allows for such delineation. Based on our data, we derived the following sequence of mTEC differentiation: TPAloMHCIIlo -> TPAloMHCIIhi -> TPAhiMHCIIhi -> TPAhiMHCIIlo Surprisingly, in the steady-state postnatal thymus TPAloMHCIIlo pre Aire rather than terminally differentiated post-Aire TPAhiMHCIIlo mTECs were marked for apoptosis at an exceptionally high rate of ~70%. Hence, only the minor cycling fraction of the MHCIIlo subset (<20%) potentially qualified as mTEC precursors. FoxN1 expression inversely correlated with the fraction of slow cycling and apoptotic cells within the four TPA subsets. TPA also further subdivided human mTECs, although with different subset distribution. Our revised road map emphazises close parallels of terminal mTEC development with that of skin, undergoing an alternative route of cell death, namely cornification rather than apoptosis. The high rate of apoptosis in pre-Aire MHCIIlo mTECs points to a "quality control" step during early mTEC differentiation. PMID- 28993520 TI - Tobacco product developments in the Australian market in the 4 years following plain packaging. AB - This paper aimed to identify continued and emerging trends in the Australian tobacco market following plain packaging implementation, over a period of substantial increases in tobacco taxes. Since 2012, our surveillance activities (including review of trade product and price lists, ingredient reports submitted by tobacco companies to government and monitoring of the retail environment) found several trends in the factory-made cigarette market. These include the continued release of extra-long and slim cigarettes and packs with bonus cigarettes, particularly in the mainstream and premium market segments; new menthol capsule products; other novel flavourings in cigarettes; filter innovations including recessed and firm filters; continued use of evocative and descriptive product names; the proliferation of the new super-value market segment; and umbrella branding, where new products are introduced within established brand families. Several similar trends were also observed within the smoking tobacco market. While not all of these trends were new to the Australian market at the time of plain packaging implementation, their continued and increased use is notable. Plain packaging legislation could be strengthened to standardise cigarette and pack size, restrict brand and variant names, and ban features such as menthol capsules and filters innovations that provide novelty value or that may provide false reassurance to smokers. PMID- 28993519 TI - Tobacco industry strategies undermine government tax policy: evidence from commercial data. AB - OBJECTIVE: Taxation equitably reduces smoking, the leading cause of health inequalities. The tobacco industry (TI) can, however, undermine the public health gains realised from tobacco taxation through its pricing strategies. This study aims to examine contemporary TI pricing strategies in the UK and implications for tobacco tax policy. DESIGN: Review of commercial literature and longitudinal analysis of tobacco sales and price data. SETTING: A high-income country with comprehensive tobacco control policies and high tobacco taxes (UK). PARTICIPANTS: 2009 to 2015 Nielsen Scantrak electronic point of sale systems data. MAIN OUTCOME MEASURES: Tobacco segmentation; monthly prices, sales volumes of and net revenue from roll-your-own (RYO) and factory-made (FM) cigarettes by segment; use of price-marking and pack sizes. RESULTS: The literature review and sales data concurred that both RYO and FM cigarettes were segmented by price. Despite regular tax increases, average real prices for the cheapest FM and RYO segments remained steady from 2013 while volumes grew. Low prices were maintained through reductions in the size of packs and price-marking. Each year, at the point the budget is implemented, the TI drops its revenue by up to 18 pence per pack, absorbing the tax increases (undershifting). Undershifting is most marked for the cheapest segments. CONCLUSIONS: The TI currently uses a variety of strategies to keep tobacco cheap. The implementation of standardised packaging will prevent small pack sizes and price-marking but further changes in tax policy are needed to minimise the TI's attempts to prevent sudden price increases. PMID- 28993521 TI - Securing a cardiology speciality training programme in the UK: how did other people do it? AB - BACKGROUND: Application to cardiology specialty training is competitive with uncertainty among candidates as to what the secret recipe for a successful appointment is. We aimed to investigate objective variables, which were demonstrated by successful appointees to cardiology training schemes in the UK. METHODS: Data from successful cardiology applicants for the years 2014 to 2016 were obtained from the Joint Royal Colleges of Physicians Training Board under the Freedom of Information Act. These data included basic demographics as well as objective scores awarded for selection categories such as qualifications, academic, teaching and other achievements. RESULTS: There were a total of 976 applicants during the study period, of whom 423 were successfully appointed, generating a competition ratio of 2.3 applicants for each position. There was an increasing proportion of successful female applicants (22% in 2014, 28% in 2015 and 32% in 2016). Median scores for postgraduate exams (14/14), presentations (6/6) and quality improvement (10/10) scores corresponded to maximum possible scores, whereas median scores for additional undergraduate and postgraduate degrees were 0. Median scores for prizes, publications and teaching experience were 6/10, 4/8 and 9/10, respectively. CONCLUSION: The secret to a successful cardiology training appointment is associated with completion of all postgraduate clinical exams, completion and presentation of quality improvement projects, national presentations and substantial teaching achievements. At least half of the successful candidates had no additional undergraduate or postgraduate degrees but had evidence of some prizes and publications. The ratio of successful female candidates is rising, but remains less than males in cardiology training. PMID- 28993522 TI - Cardiopulmonary resuscitation on television: are we miseducating the public? AB - BACKGROUND: Out-of-hospital cardiac arrest survival rates in the UK are poor, and non-medically trained individuals have been identified to perform substandard cardiopulmonary resuscitation (CPR). Millions watch televised medical dramas and, for many, these comprise their only education on CPR. This study aims to investigate the quality of CPR portrayed on these programmes and whether this has an effect on public knowledge. METHODS: Prospective observational study of 30 consecutive episodes of three popular medical dramas. Public knowledge of CPR and viewing habits were assessed with a survey of non-medically trained personnel. RESULTS: 90 episodes were reviewed with 39 resuscitation attempts shown. Chest compression rates varied from 60 to 204 compressions per minute with a median of 122 (95% CI 113 to 132). Depth varied from 1.5 to 7.5 cm with a median of 3 (3.15 4.31). Rate and depth were significantly different from the UK Resuscitation Council Guidelines (2010) (p<0.05, t-test). Survey participants (n=160, 80% response rate) documented what they thought was the correct rate and depth of chest compressions and were scored accordingly. Those who documented watching medical dramas regularly scored significantly worse than those who watched occasionally (p<0.05, Mann-Whitney test). CONCLUSION: Televised medical dramas depict CPR inaccurately and laypersons may be less well informed about the correct technique the more they tune into these programmes. While there may be other confounding variables, given the popularity of television medical dramas, the poor depiction may be significantly contributing to poor public CPR knowledge and represent a potential new avenue of public education. PMID- 28993523 TI - Giuliano Vanghetti and the innovation of "cineplastic operations". AB - OBJECTIVE: Developing functional artificial limbs for amputees has been a centuries-old challenge in medicine. We review the mechanical and neurologic principles of "cineplastic operations" and "plastic motors" used to restore movements in prostheses, with special attention to the work of Giuliano Vanghetti. METHODS: We evaluated original publications describing cineplastic operations, biographic information, writings, drawings, and unpublished letters from the Vanghetti library, preserved in Empoli, Italy, and performed a bibliographic search and comparison for similar procedures in the literature. RESULTS: Vanghetti's method for cineplastic operations differs from similar previous methods, being the first aimed at exploiting natural movements of the remnant muscles to activate the mechanical prosthesis, and the first to do so by directly connecting the prosthesis to the residual muscles and tendons. This represented a frame-changing innovation for that time and paved the way for current neuroprosthetic approaches. The first description of the method was published in 1898 and human studies started in 1900. The results of these studies were presented in 1905 and published in 1906 in Plastic and Kinematic Prosthesis. A German surgeon, Ferdinand Sauerbruch, often acknowledged as the inventor of the method, published his first results in 1915. CONCLUSIONS: Vanghetti was the first to accurately perform and describe cineplastic operations for patients following an upper arm amputation. He considered the neurologic implications of the problem and, perhaps in an effort to provide more appropriate proprioceptive feedback, he intuitively applied the prostheses so that they were functionally activated by the muscles of the proximal stump. PMID- 28993524 TI - TIPIC syndrome. PMID- 28993525 TI - Editors' Note. PMID- 28993526 TI - Letter re: Burnout, career satisfaction, and well-being among US neurologists in 2016. PMID- 28993527 TI - Letter re: Burnout, career satisfaction, and well-being among US neurologists in 2016. PMID- 28993528 TI - Letter re: Burnout, career satisfaction, and well-being among US neurologists in 2016. PMID- 28993529 TI - Letter re: Burnout, career satisfaction, and well-being among US neurologists in 2016. PMID- 28993530 TI - Letter re: Burnout, career satisfaction, and well-being among US neurologists in 2016. PMID- 28993531 TI - Author response: Burnout, career satisfaction, and well-being among US neurologists in 2016. PMID- 28993532 TI - Increased brain-predicted aging in treated HIV disease. PMID- 28993533 TI - Clinical Reasoning: A 55-year-old man with rapidly progressive dementia and parkinsonism. PMID- 28993534 TI - Teaching NeuroImages: Interferon-induced psoriasis flare in a multiple sclerosis case remits with dimethyl fumarate. PMID- 28993535 TI - Teaching NeuroImages: Giant cell arteritis presenting with acute ischemic strokes due to diffuse intracranial stenoses. PMID- 28993536 TI - Teaching NeuroImages: Spinocerebellar ataxia type 3 presenting with a cock-walk gait phenotype. PMID- 28993537 TI - Long-term treatment of patients with idiopathic pulmonary fibrosis with nintedanib: results from the TOMORROW trial and its open-label extension. AB - The TOMORROW trial of nintedanib comprised a randomised, placebo-controlled, 52 week period followed by a further blinded treatment period and an open-label extension. We assessed outcomes across these periods in patients randomised to nintedanib 150 mg twice daily or placebo at the start of TOMORROW. The annual rate of decline in FVC was -125.4 mL/year (95% CI -168.1 to -82.7) in the nintedanib group and -189.7 mL/year (95% CI -229.8 to -149.6) in the comparator group. The adverse event profile of nintedanib remained consistent throughout the studies. These results support a benefit of nintedanib on slowing progression of idiopathic pulmonary fibrosis beyond 52 weeks. PMID- 28993538 TI - Subpleural cystic change in a patient with multiple rib exostoses. PMID- 28993539 TI - Lung function response and side effects to rapamycin for lymphangioleiomyomatosis: a prospective national cohort study. AB - RATIONALE: Mechanistic target of rapamycin inhibitors reduce loss of lung function in lymphangioleiomyomatosis (LAM), although their benefit varies between individuals. We examined lung function response and side effects to rapamycin in a national cohort. METHODS: Subjects were receiving rapamycin for progressive lung disease. Clinical evaluation, detailed phenotyping, serial lung function, rapamycin and safety monitoring were performed according to a clinical protocol. Lung function change, measured as FEV1 slope (DeltaFEV1), was reported for those treated for 1 year or longer. RESULTS: Rapamycin was associated with improved DeltaFEV1 in 21 individuals where pretreatment data were available (p<0.0001). In 47 treated for a mean duration of 35.8 months, mean DeltaFEV1 was +11 (SD 75) mL/year, although it varied from +254 to -148 mL/year. The quartile with the highest positive DeltaFEV1 had greater pretreatment FEV1 (p=0.02) and shorter disease durations (p=0.02) than the lowest quartile. Serum rapamycin level was positively associated with side effects (p=0.02) but not DeltaFEV1 over 1 year. Within the first month of therapy, apthous ulcers, nausea and diarrhoea were associated with higher rapamycin levels. Acne, oedema and menstrual irregularities tended to increase over the first year of therapy. At the end of observation, the prevalence of side effects was 5% or less. CONCLUSIONS: Rapamycin reduces lung function loss in LAM, although in some, DeltaFEV1 continues to fall at an accelerated rate. Poor response to rapamycin was associated with lower pretreatment lung function and longer disease duration but not serum level. Early intervention with low-dose rapamycin may preserve lung function and reduce side effects. PMID- 28993540 TI - Quantification of CT bronchiectasis and its relationship to ventilation in cystic fibrosis. PMID- 28993541 TI - Psychiatrists' Attitude and Use of Second-generation Antipsychotics for the Treatment of Schizophrenia in Taiwan. AB - OBJECTIVES: This survey aimed to understand the attitude of psychiatrists and their use of commonly prescribed second-generation antipsychotics (SGAs) for the treatment of schizophrenia in Taiwan. It also attempted to identify the factors that might influence their preference for selecting SGAs. METHODS: Psychiatrists were interviewed face-to-face using a structured questionnaire. The questionnaire addressed various issues involved in the treatment of patients with schizophrenia, including the reasons for selecting SGAs, psychiatrists' level of satisfaction with commonly prescribed SGAs, and their current use of SGAs in clinical practice. RESULTS: Gender and age of the psychiatrists, and practice setting were not related to SGA selection. The selection of a SGA might be influenced by characteristics of the psychiatrist, properties of the drugs, and the healthcare insurance system. Most psychiatrists agreed that the performance of brand-name drugs was superior to that of generic drugs. Better symptom control, improvement in cognition, and higher tolerability were among the major factors considered by psychiatrists in Taiwan when prescribing antipsychotics. CONCLUSION: Selection of a SGA in Taiwan is potentially influenced by the characteristics of the psychiatrist, properties of the drug, and the healthcare insurance system. Efficacy and tolerability were among the major determining factors when prescribing antipsychotics for the treatment of patients with schizophrenia. PMID- 28993542 TI - Community Perceptions of Mental Illness in Jharkhand, India. AB - INTRODUCTION: Understanding and perceptions about mental illness vary among individuals based on their experience with the illness or their contact with the people affected by it. These may be further influenced by the individuals' sociocultural background. This study aimed to understand the differences in the beliefs about, understanding of, and explanations for mental illness between different population groups of Jharkhand, India. METHODS: During July 2014 to February 2016, we recruited the following 3 groups of individuals aged between 18 and 60 years: individuals with mental illness (group 1, n = 240), relatives of individuals with mental illness (group 2, n = 240), and the general public (group 3, n = 240). Qualitative and quantitative findings were combined in this study, and participants were asked about their beliefs about, understanding of, and explanations about mental illness. RESULTS: Individuals with mental illness and their relatives shared similar beliefs whereas the general public held a different opinion in various domains. There were significant differences among all groups in their understanding of various aspects of mental illnesses including the definition, causes, signs and symptoms, treatment, and outcomes. CONCLUSION: Individuals' perception towards different aspects of mental illness varies, despite they are sharing the same sociocultural milieu. Differences in beliefs, understanding, and explanations may lead to conflicts in treatment goals and expectations, and hamper the intervention strategies that promote mental health and patient care. Focused strategies to develop uniformity in beliefs and explanations about various aspects of mental illness may help to develop collaboration with different community groups that may in turn help in developing effective interventions and treatment. PMID- 28993543 TI - Psychiatric and Behavioural Problems in Children and Adolescents with Epilepsy. AB - OBJECTIVE: To investigate the psychiatric and behavioural symptoms in children and adolescents with epilepsy. METHODS: Patients with epilepsy and aged 4 to 16 years were recruited from a medical centre in Azerbaijan during January 2012 to December 2013. A community sample was drawn from 3 schools as the comparison group. The Strengths and Difficulties Questionnaire (SDQ) was administered to parents of both patients with epilepsy and children in the comparison group. The total difficulties score and the scores for each subscale were compared between the 2 groups. Additionally, scores between different groups of epileptic patients were compared. RESULTS: A total of 409 patients with epilepsy and 515 children in the comparison group were recruited. Those with epilepsy had a significantly higher mean total difficulties score and mean difficulties subscale scores (p < 0.001). In epileptic children with severe mental or physical disabilities, prosocial behaviour scores were significantly lower than those in the comparison group. The proportion of children with a total difficulties score in the abnormal range was higher in the epilepsy group than in the comparison group (53.1% vs. 15.7%; p < 0.001). Children with symptomatic epilepsy showed a higher total difficulties score than those with idiopathic epilepsy (p < 0.05). CONCLUSION: Children with epilepsy have a higher rate of psychiatric and behavioural symptoms. These rates are even higher in children with symptomatic epilepsy. PMID- 28993544 TI - Distress Related to Individual Depressive Symptoms: A Cross-sectional Study in Thai Patients with Major Depression. AB - OBJECTIVE: To examine the distress related to individual depressive symptoms, the correlation between symptom distress and disability, and the gender difference in distress levels in patients with major depressive disorder. METHODS: This was a cross-sectional, observational study carried out at a university hospital providing tertiary care in northern Thailand. Participants were patients with major depressive disorder aged between 18 and 65 years. Depression severity was self-rated using the 9-item Patient Health Questionnaire (PHQ-9). We expanded the 9 symptom items of the PHQ-9 into 13 individual symptoms. The participants rated their distress for each symptom on a scale of 0 to 4, from 0 indicating 'not at all' to 4 indicating 'extremely'. RESULTS: A total of 130 (92 female and 38 male) patients with major depressive disorder participated in this study. Of the 13 symptoms, the distress level of overeating was lowest. Compared with overeating, the distress levels of feeling depressed / hopeless, feeling guilty, poor concentration, anhedonia, initial insomnia, middle / terminal insomnia, and fatigue were significantly higher and had a large effect size of differences (p < 0.001, Cohen's dz >= 0.8). The distress levels related to feeling depressed / hopeless, feeling guilty, poor concentration, anhedonia, fatigue, suicidal ideation, and moving / speaking slowly were moderately and significantly correlated with overall functional impairment (Pearson's r = 0.31-0.48, p < 0.001). Analysis of covariance, adjusted by the PHQ-9 total score, indicated no significant difference between men and women on any symptom. CONCLUSIONS: Depressive symptoms related to high distress levels and moderately correlated with functional impairment were feeling depressed / hopeless, feeling guilty, poor concentration, and anhedonia. PMID- 28993545 TI - Folie a deux by Proxy in a Father, after Physical Abuse by a Mentally Ill Daughter. AB - This is the first case report in a country predominated by Chinese that describes the physical abuse of a recipient by the inducer in shared delusional disorder. The report describes a 42-year-old patient who physically abused her father until he submitted to her delusions. Subsequently and for years, both sustained persecutory delusions against their neighbours. While the patient was undergoing treatment, the father continued reinforcing her delusions. There is a need to explore the possibility of any forms of abuse of the recipient by the inducer in shared psychotic disorder. This report discusses the development of such delusions in a specific case and makes recommendations for the management of similar cases. PMID- 28993546 TI - Differentiation of Seromucinous Borderline Tumor from Serous Borderline Tumor on MR Imaging. AB - PURPOSE: Seromucinous borderline tumor (SMBT) is a newly categorized ovarian tumor in the 2014 revised World Health Organization (WHO) classification. SMBT is similar to serous borderline tumor (SBT) on MRI reflecting their pathological findings. This study was conducted to demonstrate the usefulness of MRI findings and quantitative values for differentiating SMBT from SBT. METHODS: This retrospective study examined 23 lesions (20 patients) from SMBT and 26 lesions (22 patients) from SBT. The following quantitative values were evaluated using receiver-operating characteristics analysis: overall and solid portion sizes, intracystic fluid signal intensity (SI) ratio compared with skeletal muscle on T1weighted image (T1WI) and T2weighted image (T2WI), contrast enhancement (CE) ratio, and mean and minimum apparent diffusion coefficient values of the solid portion. Two radiologists evaluated the prevalence of MRI finding characteristics of SMBT and SBT. The SI of the intracystic fluid on T1WI and T2WI and the association with endometriosis were evaluated visually. RESULTS: The CE ratio was significantly higher in SBT (P = 0.007). It achieved the highest area under the curve (AUC) (0.739). The fluid SI ratio on T1WI was higher in SMBT (P = 0.036, AUC = 0.676). Exophytic growth of the solid portion was observed only in SBT (P = 0.011). Intracystic fluid SI of SMBT was higher on T1WI and lower on T2WI in visual evaluation (P = 0.008 and 0.007, respectively). Findings suggesting endometriosis were observed more frequently in SMBT patients (P = 0.019). CONCLUSION: Higher CE ratio of the solid portion and exophytic growth were findings suggesting SBT. Higher intracystic fluid SI on T1WI and lower SI on T2WI suggested SMBT. MRI findings suggesting endometriosis favored the diagnosis of SMBT. PMID- 28993547 TI - Development of Novel Therapies for Cardiovascular Diseases by Clinical Application of Basic Research. AB - Cyclophilin A (CyPA) is secreted from vascular smooth muscle cells, inflammatory cells, activated platelets, and cardiac fibroblasts in response to oxidative stress. Excessive and continuous activation of the RhoA/Rho-kinase system promotes the secretion of CyPA, resulting in the development of multiple cardiovascular diseases. Basigin (Bsg), a transmembrane glycoprotein that activates matrix metalloproteinases, is an extracellular receptor for CyPA that promotes cell proliferation and inflammation. Thus, the CyPA/Bsg system is potentially a novel therapeutic target for cardiovascular diseases. Importantly, plasma CyPA levels are increased in patients with coronary artery disease, abdominal aortic aneurysms, pulmonary hypertension, and heart failure. Moreover, plasma CyPA levels can predict all-cause death in patients with coronary artery disease and pulmonary hypertension. Additionally, plasma soluble Bsg levels are increased and predict all-cause death in patients with heart failure, suggesting that CyPA and Bsg are novel biomarkers for cardiovascular diseases. To discover further novel molecules targeting the CyPA/Bsg system, high-throughput screening of compounds found molecules that ameliorate the development of cardiovascular diseases. In addition to CyPA and Bsg, novel therapeutic targets and their inhibitors for patients with pulmonary arterial hypertension have been recently screened and identified. Ultimately, the final goal is to develop novel biomarkers and medications that will be useful for improving the prognosis and quality of life in patients with cardiovascular diseases. PMID- 28993548 TI - Immunoglobulin G4-Related Cardiovascular Diseases. PMID- 28993549 TI - Isolation of equine papillomavirus type 1 from racing horse in Japan. AB - Although many studies have been conducted worldwide for Equus caballus papillomavirus (EcPV), limited information is available on the virus in Japan. We recently collected one classical viral papillomatosis sample (E150904) from a racing horse in Japan. Papillomavirus infection was confirmed by histopathology, immunohistochemistry and PCR assays, and the sample was diagnosed as epithelial papilloma. Full-length genome of the virus was cloned and sequenced. It was 7,613 bp in length and had the same genome organization with reported EcPV-1. Moreover, phylogenetic analysis based on L1 gene revealed that the infection was caused by a variant of EcPV-1. This is the first report of EcPV infection in Japan, and would further contribute to the molecular epidemiological and pathological studies for EcPV. PMID- 28993551 TI - Usefulness of Two-Compartment Model-Assisted and Static Overall Inhibitory Activity Method for Prediction of Drug-Drug Interaction. AB - Our study of drug-drug interaction (DDI) started with the clarification of unusually large DDI observed between ramelteon (RAM) and fluvoxamine (FLV). The main cause of this DDI was shown to be the extremely small hepatic availability of RAM (vFh). Traditional DDI prediction assuming the well-stirred hepatic extraction kinetic ignores the relative increase of vFh by DDI, while we could solve this problem by use of the tube model. Ultimately, we completed a simple and useful method for prediction of DDI. Currently, DDI prediction becomes more complex and difficult when examining issues such as dynamic changes in perpetrator level, inhibitory metabolites, etc. The regulatory agents recommend DDI prediction by use of some sophisticated methods. However, they seem problematic in requiring plural in vitro data that reduce the flexibility and accuracy of the simulation. In contrast, our method is based on the static and two-compartment models. The two-compartment model has advantages in that it uses common pharmacokinetics (PK) parameters determined from the actual clinical data, guaranteeing the simulation of the reference standard in DDI. Our studies confirmed that dynamic changes in perpetrator level do not make a difference between static and dynamic methods. DDIs perpetrated by FLV and itraconazole were successfully predicted by use of the present method where two DDI predictors [perpetrator-specific inhibitory activities toward CYP isoforms (pAi, CYPs) and victim-specific fractional CYP-isoform contributions to the clearance (vfm, CYPs)] are determined successively as shown in the graphical abstract. Accordingly, this approach will accelerate DDI prediction over the traditional methods. PMID- 28993552 TI - The effects of changes in the meal providing system on emergency shelter menus following the Great East Japan Earthquake. AB - Objectives To assess the improvement of the menus by the meal providing system in emergency shelters, we reanalyzed the data obtained from the dietary survey at emergency shelters in the Miyagi Prefecture one month after the Great East Japan Earthquake in 2011.Methods We performed secondary use of the dietary survey conducted by the Miyagi prefectural government. In total, 386 emergency shelters participated in the dietary survey of one day in April 2011. We examined the meal providing system (the frequency of meals per day, the frequency of mass feeding for evacuees per day, and menu creators) and the menus at each emergency shelter (260). We classified menus into the following five groups: staple foods, main dishes, side dishes, dairy products, and fruits, and calculated the frequency of provision per day.Results There was no emergency shelter that provided zero or one meal per day. Compared with the emergency shelters that provided two meals per day, shelters that provided three had a significantly higher provision frequency of staple foods. However, there were no significant differences in the provision frequencies of the other four food groups between the shelters with two or three meals per day. In emergency shelters with a higher frequency of mass feeding for evacuees, the provision frequency of four food groups (staple foods, main dishes, side dishes, and fruits) was significantly higher compared to shelter with a lower frequency of mass feeding for evacuees. Furthermore, in the emergency shelters where dietitians created menus, the provision frequency for two food groups (dairy products and fruits) was significantly higher compared to shelters without dietitians.Conclusion A high frequency of mass feeding for evacuees resulted in a high provision frequency of main dishes, side dishes, and fruits, which can be limited in supply after a disaster. Also, in the emergency shelters where dietitians created menus, the provision frequency of dairy products and fruits was higher than in those without dietitians. These results suggested that diets in the emergency shelters may be improved by mass feeding and the involvement of dietitians. PMID- 28993550 TI - Mechanism of M-cell differentiation accelerated by proliferation of indigenous bacteria in rat Peyer's patches. AB - The mechanism by which indigenous bacteria on the follicle-associated epithelium (FAE) of lymphatic follicles (LFs) accelerate the differentiation of microvillous columnar epithelial cells (MV) into M-cells was immunohistochemically investigated in rat Peyer's patches. The results showed that the number of Toll like receptor (TLR) -4+ M-cells was greater in the FAE with expansion of bacterial colonies (LFs with bacterial colonies on the FAE: b-LF) than the FAE without expansion of bacterial colonies (nb-LF). TLR-4 was also expressed in the striated borders of MV upstream next to M-cells in the FAE of the b-LF. TLR-4+ vesicles were frequently detected in the cytoplasms of MV with TLR-4+ striated borders upstream next to TLR-4+ M-cells in the FAE of b-LF. These findings suggest that TLR-4+ MV take up TLR-4 ligands and differentiate into M-cells in the b-LF. Neither the distribution of RANK nor that of RANKL was coincident with that of M-cells in the b-LF. Moreover, RANK, but not RANKL, was expressed in intestinal villi, whereas cleaved caspase-3 was immunonegative in the MV and M cells of the FAE, unlike in villous epithelial cells. Therefore, RANK/RANKL signaling in the LF might contribute to the down-regulation of epithelial apoptosis to facilitate the differentiation of MV into M-cells in rat Peyer's patches. PMID- 28993553 TI - Utilization effect of floor plan sketches in hypothetical cases assuming a community care meeting. AB - Objective Floor plan sketches (FPSs) are schematic representations of floors in a home. FPSs display information gathered from observations and interviews on people's way of dwelling. To elucidate the effects of utilizing FPSs in case reviews assuming a community care meeting attended by multidisciplinary professionals, we conducted reviews of hypothetical cases created for experimental purposes.Methods Two hypothetical cases (Cases 1 and 2) were developed, and each case was reviewed with and without FPSs. Two groups (Groups A and B) were created, each consisting of five health care and welfare professionals involved in actual case reviews. Group A reviewed Case 1 without FPSs followed by Case 2 with FPSs, while Group B reviewed Case 2 without FPSs followed by Case 1 with FPSs. Case conferences and group interviews conducted after the completion of these reviews. Based on the verbatim transcripts of the reviews and interviews, we investigated differences between case reviews with and without FPSs with regard to the time required for the review and the number and contents of participants' comments.Results Review content could largely be divided into two categories: (1) the living conditions and support for the case subjects and their families, and (2) their homes and their way of dwelling at home. These categories were common to case reviews both with and without FPSs. In discussions about the homes and ways of dwelling, however, confirmation of the locations of rooms consumed a large amount of time in case reviews without FPSs. In case reviews with FPSs, discussions were more specific and included details such as room usage and paths by which residents move. The mean time required for a review was 41 minutes per case (range: 36 to 44 minutes), which did not greatly differ based on whether or not FPSs were used. Participants made more comments and seemed to interact more actively with each other when they had the FPSs than when they did not. The impressions of participants were that FPSs allowed the visualization of the case subjects and their families in their homes and fostered a greater feeling of familiarity with the case.Conclusion The use of FPSs in case reviews reduces the time spent on information sharing and allows more detailed review contents. Furthermore, FPSs enhance the ability to imagine the daily lives of case subjects and their families, thereby potentially broadening assessments in case reviews. PMID- 28993554 TI - The concept of food risk, knowledge, awareness, and behavior of preschool children's mothers. PMID- 28993555 TI - Complete chloroplast genome and 45S nrDNA sequences of the medicinal plant species Glycyrrhiza glabra and Glycyrrhiza uralensis. AB - Glycyrrhiza uralensis and G. glabra, members of the Fabaceae, are medicinally important species that are native to Asia and Europe. Extracts from these plants are widely used as natural sweeteners because of their much greater sweetness than sucrose. In this study, the three complete chloroplast genomes and five 45S nuclear ribosomal (nr)DNA sequences of these two licorice species and an interspecific hybrid are presented. The chloroplast genomes of G. glabra, G. uralensis and G. glabra * G. uralensis were 127,895 bp, 127,716 bp and 127,939 bp, respectively. The three chloroplast genomes harbored 110 annotated genes, including 76 protein-coding genes, 30 tRNA genes and 4 rRNA genes. The 45S nrDNA sequences were either 5,947 or 5,948 bp in length. Glycyrrhiza glabra and G. glabra * G. uralensis showed two types of nrDNA, while G. uralensis contained a single type. The complete 45S nrDNA sequence unit contains 18S rRNA, ITS1, 5.8S rRNA, ITS2 and 26S rRNA. We identified simple sequence repeat and tandem repeat sequences. We also developed four reliable markers for analysis of Glycyrrhiza diversity authentication. PMID- 28993556 TI - Telomere biology in aging and cancer: early history and perspectives. AB - The ends of eukaryotic linear chromosomes are protected from undesired enzymatic activities by a nucleoprotein complex called the telomere. Expanding evidence indicates that telomeres have central functions in human aging and tumorigenesis. While it is undoubtedly important to follow current advances in telomere biology, it is also fruitful to be well informed in seminal historical studies for a comprehensive understanding of telomere biology, and for the anticipation of future directions. With this in mind, I here summarize the early history of telomere biology and current advances in the field, mostly focusing on mammalian studies relevant to aging and cancer. PMID- 28993557 TI - Biological functions of glucolipids in Bacillus subtilis. AB - Glyceroglycolipids are very important in Gram-positive bacteria and cyanobacteria. In Bacillus subtilis, a model organism for the Gram-positive bacteria, the ugtP mutant, which lacks glyceroglucolipids, shows abnormal morphology. Lack of glucolipids has many consequences: abnormal localization of the cytoskeletal protein MreB and activation of some extracytoplasmic function (ECF) sigma factors (sigmaM, sigmaV and sigmaX) in the log phase are two examples. Conversely, the expression of monoglucosyldiacylglycerol (MGlcDG) by 1,2-diacylglycerol 3-glucosyltransferase from Acholeplasma laidlawii (alMGS) almost completely suppresses the ugtP disruptant phenotype. Activation of ECF sigmas in the ugtP mutant is decreased by alMGS expression, and is suppressed to low levels by MgSO4 addition. When alMGS and alDGS (A. laidlawii 1,2 diacylglycerol-3-glucose (1-2)-glucosyltransferase producing diglucosyldiacylglycerol (DGlcDG)) are simultaneously expressed, sigmaX activation is repressed to wild type level. These observations suggest that MGlcDG molecules are required for maintenance of B. subtilis cell shape and regulation of ECF sigmas, and that DGlcDG regulates sigmaX activity. The activation of ECF sigmas is not accompanied by proteolysis of anti-sigma. Thus, glyceroglucolipids may have the specific role of helping membrane proteins function by acting in the manner of chaperones. PMID- 28993560 TI - Clinical Applicability and Psychometric Properties of Manual Function Test for Patients with Stroke. AB - The Manual Function Test (MFT) is a tool to assess upper extremity motor impairment associated with stroke. This study investigated psychometric properties of the Korean version of the MFT and to establish normative data. Eighty-one patients were enrolled to evaluate MFT, Fugl-Meyer Assessment (FMA) and manual muscle test (MMT). MFT was completed by eight raters on two occasions separated by 6 weeks. Absolute and relative reliability and validity were examined. Additionally, MFT was assessed on 75 healthy controls of different ages. Intraclass correlation coefficient (ICC) (2,1) values for total and each dimension of Korean MFT ranged from 0.984 to 0.998 in the affected side of hemiplegic patients, indicating inter-rater reliability. Percentage values of standard error of measurement (SEM) and smallest real difference (SRD) ranged 3.10-10.57% and 8.58-29.29% respectively. Test-retest reliability ICCs for all raters were above 0.98. Effect size (ES) and standardized response mean (SRM) were larger in the acute-subacute group (onset to initial evaluation <= 4 months) (ES = 0.12; SRM = 0.41) than those in the chronic group (onset to evaluation > 4 months) (ES = 0.01; SRM = 0.11). MFT score was significantly correlated with FMA score (p < 0.001) and MMT score (p < 0.001). In healthy controls, regression analysis indicated that age significantly predicts manual function scores on both dominant and non-dominant. The Korean MFT showed good reliability and validity. Modest responsiveness was observed in patients evaluated early after stroke onset. The Korean MFT is useful in evaluating upper extremity motor deficits for clinical and research purposes. PMID- 28993561 TI - A Missense Variant rs4645843 in TNF-alpha Gene Is a Risk Factor of Polycystic Ovary Syndrome in the Uygur Population. AB - Polycystic ovary syndrome (PCOS) is a complex endocrine syndrome, resulting from the interaction of gene variants and environmental factors. PCOS is viewed as a proinflammatory state and is characterized by hyperandrogenism, hyperinsulinemia, and over-weight. In China, the incidence of PCOS is higher in the Uygur population than that in the Chinese Han population. The association of the tumor necrosis factor alpha (TNF-alpha) gene with PCOS remains to be clarified. Here, we investigated the association of TNF-alpha polymorphisms with PCOS in the Uygur population (393 patients with PCOS and 381 healthy subjects). Two single nucleotide polymorphisms in TNF-alpha were analyzed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method: rs1800629 (-308G/A polymorphism), a commonly tested variant and rs4645843 (6213C/T polymorphism) that causes a Pro-to-Leu substitution at position 84, the most damaging variant of TNF-alpha based on in silico analysis. We thus found that both the genotypic and allelic distributions of rs4645843 were significantly different between PCOS and control groups (p = 0.03 and 0.024, respectively), whereas those of rs1800629 were similar between the groups. Furthermore, rs4645843 was significantly associated with serum testosterone levels and the score of Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), but no such association was found with rs1800629. Importantly, both rs4645843 and rs1800629 were significantly associated with higher body mass index (p < 0.05). This is the first study that shows the association of TNF-alpha gene with PCOS in the Uygur population. The TNF-alpha gene may influence the pathogenesis of PCOS through regulating testosterone level, obesity and HOMA-IR. PMID- 28993559 TI - Carboxyethylgermanium sesquioxide (Ge-132) treatment during in vitro culture protects fertilized porcine embryos against oxidative stress induced apoptosis. AB - Compared with the in vivo environment, porcine in vitro embryo-culture systems are suboptimal, as they induce oxidative stress via the accumulation of reactive oxygen species (ROS). High ROS levels during early embryonic development cause negative effects, such as apoptosis. In this study, we examined the effects of the antioxidant carboxyethylgermanium sesquioxide (Ge-132) during in vitro culture (IVC) on embryonic development in porcine in vitro fertilization (IVF) embryos. Zygotes were treated with different concentrations of Ge-132 (0, 100, 200 and 400 MUg/ml). All of the Ge-132 treatment groups displayed greater total cell numbers after IVC (98.1, 98.5 and 103.4, respectively) compared with the control group (73.9). The 200 MUg/ml Ge-132 treatment group exhibited significantly increased intracellular GSH levels compared with the control group, whereas the ROS generation levels decreased in Ge-132 dose-dependent manner (P < 0.05). The mRNA expression levels of the KEAP1 gene and proapoptotic genes BAX and CASPASE3 were lower in the Ge-132 treated blastocysts compared with the control group (P < 0.05). The percentages of apoptotic and necrotic cells in the Ge-132 treated embryos on day 2 (48 h) were significantly lower than the untreated embryos (9.1 vs. 17.1% and 0 vs. 2.7%, respectively). In the day 7 blastocysts, the percentages of apoptotic cells in 200 ug/ml Ge-132 treated group were lower compared to controls (1.6 vs. 2.5%). More KEAP1 protein was found to be localized in cytoplasm of the 200 MUg/ml Ge-132 treated blastocysts, whereas KEAP1 protein was predominantly nuclei in the control blastocysts. These results indicate that the developmental competence of embryos cultured under Ge-132 treatment may be associated with KEAP1 signaling cascades involved in oxidative stress and apoptosis during porcine preimplantation embryo development. PMID- 28993562 TI - Ultrastructural features of canine neuroaxonal dystrophy in a Papillon dog. AB - Neuroaxonal dystrophy (NAD) is a neurodegenerative disease characterized by severe axonal swelling (spheroids) throughout the nervous system. In dogs, NAD has been reported in several breeds and a missense mutation in PLA2G6 gene has recently been identified in the Papillon dog NAD. Here we performed ultrastructural analysis to clarify the detailed ultrastructural features of the Papillon dog NAD. Dystrophic axons consisted of accumulation of filamentous materials, tubulovesicular structures, and swollen edematous mitochondria with degenerated inner membranes were often observed in the central nervous system. At axonal terminals, degeneration of presynaptic membrane was also detected. As reported in Pla2g6 knockout mice, mitochondrial and presynaptic degeneration may be related with the pathogenesis of NAD in Papillon dogs. PMID- 28993563 TI - MRI Findings Consistent with Peripatellar Fat Pad Impingement: How Much Related to Patellofemoral Maltracking? AB - Peripatellar fat pads are intracapsular extrasynovial adipose cushions that accommodate the changing shape and volume of articular spaces during movement. Variations in bone geometry, passive and active stabilization mechanisms and/or functional demands may lead to peripatellar fat pad abnormalities. While peripatellar fat pads may be affected a variety of conditions such as synovial inflammation, tumor and fibrosis, a mechanical origin should also be considered. Commonly, the clinical term "impingement" is used synonymously in the radiological literature to refer to three distinct entities of structural peripatellar fat pad abnormalities: superolateral the infrapatellar fat pad (Hoffa fat pad) edema, suprapatellar fat pad edema, and prepatellar fat pad edema, implying a mechanical origin of these conditions. The aim of this pictorial review is to describe the normal anatomy of the extensor mechanism of the knee, and discuss the relation of patellofemoral maltracking to the above mentioned peripatellar fat pad conditions based on current evidence. PMID- 28993564 TI - Swine used in the medical university: overview of 20 years of experience. AB - Center for Development of Advanced Medical Technology (CDAMTec) in Jichi Medical University was established in 2009. It is the first educational research facility specialized for medical research and training using swine in Japan. Preclinical studies on large animals are essential prior to clinical trials to develop regenerative medical products and medical equipment. We have continued comprehensively considering using miniature swine for experiments to develop advanced medical technologies and train physicians with advanced clinical abilities, while paying attention to animal welfare. The center plays a pioneering role in this field by accumulating know-how such as (1) Construction and effective utilization of research facilities, (2) Procurement of quality animal resources, (3) Education and training of technical staff, (4) Establishment of support system for physicians and researchers. We now open up widely these expertise and foundation for medical research and training not only within our university but also outside the university, so as to move faster to practical use of advanced medical technology and contribute to human health and welfare. PMID- 28993565 TI - A retrospective study of radiographic abnormalities in the repositories for Thoroughbreds at yearling sales in Japan. AB - This study aimed to evaluate whether radiographic abnormalities at yearling sales were associated with the failure to start racing at 2-3 years of age. Radiographic abnormalities in the carpal (n=852), tarsal (n=976), metacarpophalangeal (n=1,055), and metatarsophalangeal joints (n=1,031) from 1,082 horses, recorded at yearling sale, were reviewed. Eighty-two horses (7.6%) failed to start racing. Radiographic abnormalities such as wedged or collapsed tarsal bones, irregular lucency of a sagittal ridge at the distal aspect of the distal third metatarsal bone, and proximal dorsal fragmentation of the first phalanx in metatarsophalangeal joints were associated with failure to start racing in these horses. In the follow-up survey of 12 horses with one or more these radiographic abnormalities, the horses failed to start racing due to reasons unrelated to these radiographic abnormalities such as pelvic fractures (2 horses), fracture of a distal phalanx (1 horse), cervical stenotic myelopathy and proximal sesamoid fracture (1 horse), superficial digital flexor tendonitis (2 horses), laryngeal hemiplegia (1 horse), economic problems (2 horses) and unknown causes (3 horses). Although radiographic abnormalities at yearling sales can be associated with failure to start racing at 2-3 years of age, these radiographically detected abnormalities might not necessarily cause that failure. PMID- 28993566 TI - Fecal microbiome in dogs with inflammatory bowel disease and intestinal lymphoma. AB - Although alteration of commensal microbiota is associated with chronic gastrointestinal (GI) diseases such as inflammatory bowel disease (IBD) in dogs, the microbiota composition in intestinal lymphoma, an important differential diagnosis of canine IBD, has not been investigated. The objective of this study was to compare the fecal microbiota in dogs with IBD, dogs with intestinal lymphoma, and healthy dogs. Eight dogs with IBD, eight dogs with intestinal lymphoma, and fifteen healthy dogs were included in the study. Fecal samples were analyzed by 16S rRNA gene next-generation sequencing. Rarefaction analysis failed to reveal any difference in bacterial diversity among healthy dogs and diseased dogs. Based on PCoA plots of unweighted UniFrac distances, the bacterial composition in dogs with intestinal lymphoma was different from those observed in dogs with IBD and healthy dogs. When compared with healthy dogs, intestinal lymphoma subjects showed significant increases in organisms belonging to the Eubacteriaceae family. The proportion of the family Paraprevotellaceae and the genus Porphyromonas was significantly higher in dogs with IBD compared to healthy dogs. These observations suggest that dysbiosis is associated with intestinal lymphoma as well as IBD in dogs. PMID- 28993567 TI - Reference intervals and allometric scaling of two-dimensional echocardiographic measurements in 150 healthy cats. AB - The objective of the study was to evaluate the effects of body weight (BW), breed, and sex on two-dimensional (2D) echocardiographic measures, reference ranges, and prediction intervals using allometrically-scaled data of left atrial (LA) and left ventricular (LV) size and LV wall thickness in healthy cats. Study type was retrospective, observational, and clinical cohort. 150 healthy cats were enrolled and 2D echocardiograms analyzed. LA diameter, LV wall thickness, and LV dimension were quantified using three different imaging views. The effect of BW, breed, sex, age, and interaction (BW*sex) on echocardiographic variables was assessed using univariate and multivariate regression and linear mixed model analysis. Standard (using raw data) and allometrically scaled (Y=a * Mb) reference intervals and prediction intervals were determined. BW had a significant (P<0.05) independent effect on 2D variables whereas breed, sex, and age did not. There were clinically relevant differences between reference intervals using mean +/- 2SD of raw data and mean and 95% prediction interval of allometrically-scaled variables, most prominent in larger (>6 kg) and smaller (<3 kg) cats. A clinically relevant difference between thickness of the interventricular septum (IVS) and dimension of the LV posterior wall (LVPW) was identified. In conclusion, allometric scaling and BW-based 95% prediction intervals should be preferred over conventional 2D echocardiographic reference intervals in cats, in particular in small and large cats. These results are particularly relevant to screening examinations for feline hypertrophic cardiomyopathy. PMID- 28993568 TI - Antibody response to equine coronavirus in horses inoculated with a bovine coronavirus vaccine. AB - A vaccine for equine coronavirus (ECoV) is so far unavailable. Bovine coronavirus (BCoV) is antigenically related to ECoV; it is therefore possible that BCoV vaccine will induce antibodies against ECoV in horses. This study investigated antibody response to ECoV in horses inoculated with BCoV vaccine. Virus neutralization tests showed that antibody titers against ECoV increased in all six horses tested at 14 days post inoculation, although the antibody titers were lower against ECoV than against BCoV. This study showed that BCoV vaccine provides horses with antibodies against ECoV to some extent. It is unclear whether antibodies provided by BCoV vaccine are effective against ECoV, and therefore ECoV challenge studies are needed to evaluate efficacy of the vaccine in the future. PMID- 28993569 TI - Immunolocalization of beta-catenin, E-cadherin and N-cadherin in neonate and adult rat kidney. AB - beta-catenin, E-cadherin and N-cadherin are adhesion molecules that play important roles in organogenesis, tissue homeostasis, renal epithelial integrity and polarity. The present study demonstrated their immunolocalization in adult and neonate rat kidney. Membranous or cytoplasmic expression of beta-catenin, E cadherin and N-cadherin were seen in adult and developing renal tubular epithelial cells. Particularly, in adult kidney, E-cadherin and beta-catenin were intensively expressed in distal renal tubules, whereas N-cadherin was expressed in proximal renal tubules. In neonate rat kidney on 1 and 4 days old, developing renal tubular epithelial cells were mainly reacted with E-cadherin and very weakly expressed N-cadherin; beta-catenin was expressed in developing renal tubules and mesenchymal blastemal cells. Interestingly, beta-catenin-positive renal tubular epithelial cells simultaneously expressed E-cadherin in the kidney of adult and developing rats. Collectively, the adhesion molecules were differentially distributed in the renal tubules of adult rats and beta-catenin and E-cadherin are predominant adhesion molecules in developing kidney. The present findings would provide the basic information of evaluating renal tubular toxicity using rats, in addition to renal genesis, in terms of adhesion molecules. PMID- 28993570 TI - Competencies required for occupational health nurses. AB - OBJECTIVES: For occupational health (OH) nurses to perform activities effectively, not only skills and knowledge but also competencies proposed by Dr. McClelland are indispensable. This study aimed to identify competencies required for OH nurses and to show their structure diagram. METHODS: Qualitative descriptive research was conducted from October 2010 to August 2011. Eight high performing OH nurses participated, and data were collected from semi-structured interviews held for each nurse. Data were qualitatively and inductively analyzed using the KJ method. RESULTS: Seven competencies were identified: "self-growth competency," "OH nursing essence perpetuation competency," "strategic planning and duty fulfillment competency," "coordination competency," "client growth support competency," "team empowerment competency," and "creative competency." A structure diagram of the seven competencies was clarified. As the definitions of the competencies were different, the findings of competencies for OH nursing in the United States of America (USA) could not simply be compared with the findings of our study; however, all seven competencies were compatible with those in AAOHN model 1 and AAOHN model 2 in the USA. CONCLUSION: Our seven competencies are essential for OH nurses to perform activities that meet the expectations of employees and the employer. PMID- 28993571 TI - Job safety analysis and hazard identification for work accident prevention in para rubber wood sawmills in southern Thailand. AB - OBJECTIVE: We utilized job safety analysis (JSA) and hazard identification for work accident prevention in Para rubber wood sawmills, which aimed to investigate occupational health risk exposures and assess the health hazards at sawmills in the Trang Province, located in southern Thailand. METHODS: We conducted a cross sectional study which included a walk-through survey, JSA, occupational risk assessment, and environmental samplings from March through September 2015 at four Para rubber wood sawmills. RESULTS: We identified potential occupational safety and health hazards associated with six main processes, including: 1) logging and cutting, 2) sawing the lumber into sheets, 3) planing and re-arranging, 4) vacuuming and wood preservation, 5) drying and planks re-arranging, and 6) grading, packing, and storing. Working in sawmills was associated with high risk of wood dust and noise exposure, occupational accidents injuring hands and feet, chemicals and fungicide exposure, and injury due to poor ergonomics or repetitive work. DISCUSSION: Several high-risk areas were identified from JSA and hazard identification of the working processes, especially high wood dust and noise exposure when sawing lumber into sheets and risk of occupational accidents of the hands and feet when struck by lumber. All workers were strongly recommended to use personal protective equipment in any working processes. Exposures should be controlled using local ventilation systems and reducing noise transmission. We recommend that the results from the risk assessment performed in this study be used to create an action plan for reducing occupational health hazards in Para rubber sawmills. PMID- 28993572 TI - Exposure assessment of carbon nanotubes at pilot factory focusing on quantitative determination of catalytic metals. AB - OBJECTIVES: The application of multiwall carbon nanotubes (MWCNTs) currently extends to various fields. However, it has been reported that exposure to CNT causes hazardous effects on animals and cells. The purpose of this study was to quantify the exposure to MWCNT in MWCNT/polymer composites for exposure assessment. We focused on catalytic metals included in the MWCNT and the diameter of dust released during the working processes. Although the Co in MWCNTs is not a common catalyst, it was used as a tracer in this study. METHODS: A field survey was conducted in a MWCNT/polymer composite pilot factory. Airborne MWCNTs were monitored using black carbon monitors (BCMs) and optical particle sizers (OPSs) and collected on a filter. The MWCNT powder, all polymer resins used during the working processes, and the filter were analyzed in our lab using inductively coupled plasma mass spectrometry (ICP-MS) and electron microscopic observation. RESULTS: The mean concentration of airborne MWCNT contained in the collected dust was 0.92 MUg/m3 a few meters away from the extruder during the working processes (using elemental analysis). The maximum concentration measured using BCMs was shown to be seven times higher than the base concentration during the pelletizing process of polycarbonate (PC) and MWCNT composites. However, free, isolated, and unbound agglomerated MWCNTs were not detected using scanning electron microscopic (SEM) observation. CONCLUSIONS: The result obtained by elemental analysis indicated it was possible to quantify MWCNT in composites. The mean concentration at this factory was lower than the recommended exposure limit. However, additional studies during the pelletizing process are required in the future. PMID- 28993573 TI - Measurement of nanoparticle exposure in crematoriums and estimation of respiratory deposition of the nanoparticles by number and size distribution. AB - OBJECTIVES: Nanoparticles (NPs), including hazardous substances, are generated in crematoriums due to the high temperatures during the combustion process. NPs are reported to greatly impact animals' health by reaching the alveoli and being carried to the entire body through the blood stream. However, studies in crematoriums have yet to assess workers' exposure to the generated NPs. The purpose of this study is to assess workers' exposure to NPs released in crematoriums. METHODS: Field surveys were conducted in three crematoriums with an emphasis on cremation, bone rearrangement and cleaning processes. The NP concentrations and size distributions were analyzed. The deposition of NPs in each respiratory region during each working process was calculated based on the measured data using the Human Respiratory Tract Model. RESULTS: The mean particle number concentration was maximized momentarily during the bone rearrangement process. The concentration at the time a crematory's door was opened was 500,000 particle/cm3. NPs aggregated to micro-sized particles within a few minutes, dust generated by the bone rearrangement, or both. As a result of model calculation, the mean ratios (alveolar per the other regions by a crematory) were approximately 3.0 (bronchus and bronchioles regions: except for the first survey in crematorium A which had the obstruction of measurement) and 4.3 (extrathoracic airways). The ratios were similar for all crematoriums. CONCLUSIONS: These results can be used for health risk assessments in crematoriums. In addition, these results should be applicable to estimate the inhalation unit risk of each respiratory organ such as lungs and nose. PMID- 28993574 TI - Systematic review of the association between physical activity and burnout. AB - OBJECTIVE: Burnout constitutes a health risk, and interventions are needed to reduce it. The aim of this study was to synthesize evidence regarding the relationship between physical activity and burnout by conducting a systematic review of longitudinal and intervention studies. METHODS: A literature search resulted in the identification of a final set of ten studies: four longitudinal and six intervention studies. In separate analyses for each category, evidence was synthesized by extracting the study characteristics and assessing the methodological quality of each study. The strength of evidence was calculated with the standardized index of convergence (SIC). RESULTS: In longitudinal studies, we found moderately strong evidence (SIC (4) = -1) for a negative relationship between physical activity and the key component of burnout, i.e., exhaustion. We found strong evidence (SIC (6) = -0.86) for the effect of physical activity on reducing exhaustion in intervention studies. As only one study could be classified as a high quality study, these results of previous studies need to be interpreted with some caution. CONCLUSIONS: This systematic review suggests that physical activity constitutes an effective medium for the reduction of burnout. Although consistent evidence was found, there is a lack of high quality longitudinal and intervention studies considering the influence of physical activity on burnout. Therefore, future research should be conducted with the aim to produce high quality studies, to develop a full picture of physical activity as a strategy to reduce burnout. PMID- 28993576 TI - Prevention of alcohol-related health harm in the workplace. PMID- 28993575 TI - The reciprocal relationship between sickness presenteeism and psychological distress in response to job stressors: evidence from a three-wave cohort study. AB - OBJECTIVES: Sickness presenteeism (SP) is postulated as workers' response to their general state of health; hence, SP is expected to affect workers' future health. In the present study, we examined the reciprocal relationship between SP and health in response to job stressors, with specific reference to psychological distress (PD) as workers' state of health. METHODS: We conducted mediation analysis, using data from a three-wave cohort occupational survey conducted at 1 year intervals in Japan; it involved 1,853 employees (1,661 men and 192 women) of a manufacturing firm. We measured SP and PD, using the World Health Organization Health and Work Performance Questionnaire and Kessler 6 score, respectively. For job stressors, we considered job demands and control, effort and reward, and procedural and interactional justice. RESULTS: PD mediated 11.5%-36.2% of the impact of job control, reward, and procedural and interactional justice on SP, whereas SP mediated their impact on PD, albeit to a much lesser extent in the range of 3.4%-11.3%. Unlike in the cases of these job stressors related to job resources, neither SP nor PD mediated the impact of job demands or effort. CONCLUSIONS: Our results confirmed the reciprocal relationship between SP and PD in response to selected types of job stressors, emphasizing the need for more in depth analysis of the dynamics of these associations. PMID- 28993577 TI - Effect of Biochanin A versus 17beta estradiol in rat submandibular salivary gland. AB - The epigenetic nature of development mandates the observation of the effect of any exogenous substance, especially those with estrogenic activities, during critical phases of development. The submandibular gland (SMG) presents as a great model due to extensive postnatal development, and is known to be regulated and affected by hormones as well as growth factors. Herein, we observed postnatal development following low doses of Biochanin A (BCA) and 17beta estradiol (E2) in rats. The pups were randomly divided into four groups: control, BCA, E2, and dimethyl sulfoxide (DMSO), and euthanized at the 6th, 15th, 30th, and 60th postnatal days (PND). SMG morphogenesis was assessed. The nuclear expression of estrogen receptor beta (ERbeta) was evaluated immunohistochemically; ERbeta expression was up-regulated by BCA and down-regulated by E2. Similarly, caspase three gene expression, assessed by real time polymerase chain reaction was increased in the BCA group but decreased in the E2 group. A significant decrease in epidermal growth factor gene expression was noted at PND 30. The results presented by this study provide evidence that the effect of a postnatal exposure of the SMG to Biochanin A during development could be linked to sex hormone dependent disorders. PMID- 28993578 TI - Characterizations of oral microbiota in elderly nursing home residents with diabetes. AB - Over 700 bacterial species have been detected in the oral cavity. Several studies have suggested that periodontitis is associated with systemic disorders such as diabetes mellitus, indicating a key role for oral microbiota in human health. However, the relationship between oral microbiota and diabetes has not been well clarified. Therefore, we conducted microbiome analysis of saliva samples obtained from 15 elderly residents (3 with type 2 diabetes mellitus [DM] and 12 without diabetes [non-DM]) at three different nursing homes, as well as 9 young healthy controls (HC). Genomic DNA was extracted from each sample, and then the V4 region of the 16S rRNA gene was amplified and sequenced. Alpha diversity, in terms of operational taxonomic unit richness, was significantly higher in samples from the non-DM group than in those from the HC group. Weighted UniFrac distance analysis showed that salivary microbial communities in the DM group were separately clustered. Furthermore, in the DM group, Actinomyces and Selenomonas showed significantly higher abundance, whereas Alloprevotella showed significantly lower abundance, relative to the non-DM group. Although our findings were limited by the small sample size, oral bacterial diversity in the DM group was clearly different from that in the non-DM group. PMID- 28993579 TI - Role of orexin receptor subtypes in the inhibitory effects of orexin-A on potassium chloride-induced increases in intracellular calcium ion levels in neurons derived from dorsal root ganglion of carrageenan-treated rats. AB - We analysed the roles of orexin receptors in the effects of orexin-A on KCl induced increases in intracellular calcium ion levels ([Ca2+]i) in C-fiber-like small neurons of rats with inflammation induced by intraplantar injection of carrageenan into the hind paw. Controls were treated with saline. Paw withdrawal and threshold forces in response to tactile stimuli were determined using von Frey filaments. [Ca2+]i in C-fiber-like neurons derived from dorsal root ganglia was visualised using a calcium fluorescence probe. Changes in neuronal [Ca2+]i were assessed as relative fluorescence intensity (F/F0). One day after carrageenan injection, the paw withdrawal response to tactile stimuli and the paw withdrawal threshold were increased and reduced, respectively. KCl loading of neurons from either carrageenan-treated or control rats increased F/F0 to about 2.0. KCl-induced increases in F/F0 of carrageenan-treated, but not control, rats were inhibited by orexin-A. The OX1 and OX2 receptor antagonist MK-4305, but not the OX1 receptor antagonist SB334867, counteracted the effects of orexin-A on the KCl-induced increase in F/F0. These results suggest that OX2, but not OX1 receptors mediate the inhibitory effect of orexin-A on KCl-induced increases in [Ca2+]i in C-fiber-like neurons of rats with inflammation. PMID- 28993580 TI - Inductively Coupled Plasma-Mass Spectrometry. PMID- 28993581 TI - Quantitative Detection of Ambroxol in Human Plasma Using HPLC-APCI-MS/MS: Application to a Pharmacokinetic Study. AB - In this study, a rapid and reliable high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for the determination of ambroxol in human plasma was developed and validated using palmatine as an internal standard (IS). Ambroxol and IS were extracted from 200 MUL of human plasma via a simple protein precipitation preparation. Chromatographic separation was achieved on a Platisil C18 column (150 * 4.6 mm, 5 MUm) using methanol-0.01% formic acid (70:30, v/v) as the mobile phase at a flow rate of 0.6 mL/min under an isocratic condition. The MS acquisition m/z 379 -> 264 for ambroxol and 352 -> 336 for IS was performed by atmospheric-pressure chemical ionization (APCI) mass spectrometry in selected reaction monitoring mode. The calibration curve for ambroxol was linear over the concentration range of 2.500 - 180.0 ng/mL. The matrix effects of ambroxol ranged from 104.6 to 112.7%. This fully validated method was successfully applied to a pharmacokinetic study of ambroxol in humans after oral administration of ambroxol at a single dose of 75 mg. PMID- 28993582 TI - A Study of Electrochemical Sensor Based on BHb-imprinted Magnetic Nanoparticles. AB - A study of an electrochemical sensor based on bovine hemoglobin (BHb) imprinted magnetic nanoparticles (MIPs) was investigated. First, BHb MIPs were successfully synthesized with magnetic Fe3O4@Au nanoparticles as carrier by surface modification of mercapto propionic acid for introducing carboxyl groups, combined with dopamine as the functional monomer and BHb as the template protein. Then, the MIPs were modified to the surface of a glassy carbon electrode (GCE) for electrochemical analysis by using cyclic voltammetry in the potassium ferricyanide solution. Results show that there was a good dynamic response between electrochemical signals and the adsorption amount of protein in the range of 0.05 to 0.5 mg mL-1. Results show that the sensor exhibits a significant specific recognition toward the template protein via selective test and can be used for analysis of serum samples. The synthesized MIPs are suitable for the removal and enrichment of template protein in proteomics. At the same time, the proposed electrochemical sensor can be used for recognition of BHb. PMID- 28993583 TI - Immunoassay for Human IgG Using Antibody-functionalized Silver Nanoparticles. AB - A simple colorimetric immunoassay for quantification of human immunoglobulin G (hIgG) is herein described. The assay is based on the aggregation inhibition of silver nanoparticles (AgNP) functionalized with hIgG antibody (anti-hIgG) on the surface. The aggregation is measured in terms of attenuance values ratio at 400 and 530 nm (A400/A530). A linear response between A400/A530 and hIgG concentration is observed in the range 25 - 200 ng mL-1, and the detection limit is estimated as 11 ng mL-1 hIgG. PMID- 28993584 TI - Simultaneous Production and Surface Functionalization of Silver Nanoparticles for Label-free Colorimetric Detection of Copper Ion. AB - In this work, a simple method was developed to simultaneously fabricate silver nanoparticles (AgNPs) and modify their surfaces with recognition functional groups for colorimetric detection of Cu2+ ions. To prepare the AgNPs with proper functional group on their surface for detection of Cu2+ ions, photochemical reaction was employed and a photoactive species of tyrosine (Tyr) was used to trigger the photoreduction of AgNPs, while the oxidized Tyr (TyrOx) was used to functionalize the AgNPs surface at the same time. To understand the behaviors, the prepared color AgNPs colloidal solution was characterized by UV-visible spectrometer, FT-IR spectrometer, dynamic light scattering (DLS), X-ray photoelectron spectrometer (XPS) and density functional theory (DFT). Based on DFT calculation results, TyrOx was adsorbed on the surface of AgNPs by the quinone ring and its functional group of amino acid was freely exposed to the aqueous media for rapid interaction of Cu2+ ions. Based on detection of different metal ions, TyrOx@AgNPs were selective to interact with Cu2+ ions through formation of highly stable Cu2+-TyrOx@AgNPs complexes. The evidence in formation of Cu2+-TyrOx@AgNPs complex could be obtained through the red shift of the surface plasmonic resonance (SPR) band of TyrOx@AgNPs located at 557 nm, which gives a color change from light yellow to brown color allowing visual identification of Cu2+ ions for rapid screening purposes. For quantitative analysis, a band intensity ratio of A557/(A404-A557) was constructed to correlate with the concentration of Cu2+ ions. A linear range up to 10 MUM with a detection limit close to 150 nM was found. PMID- 28993586 TI - Synthesis of Carbon Dots Originated from Hydroxypropylmethyl Cellulose for Sensing Ciprofloxacin. AB - Hereby, one kind of facile carbon dots (CDs) from hydroxypropylmethyl cellulose (HPMC) has been successfully provided, which obviously emitted blue fluorescence. With the related characterizations in detail, the CDs prepared here mainly consisted of C and O, owing to the functional groups of -OH and C=O on their surfaces. Likewise, the CDs also showed multiple advantages, including excellent photostability, superior dispersity and desirable stability. Moreover, the CDs were applied for sensing ciprofloxacin due to forming complexes with ciprofloxacin, thus leading to the fluorescence quenching of CDs. This proposed method was permitted to sense ciprofloxacin in a linear range of 10 nM L-1 - 90 MUM L-1, suggesting that it may broaden the sensing ways for assaying ciprofloxacin. PMID- 28993585 TI - Determination of Brilliant Blue FCF by a Novel Solid-state ECL Quenching Sensor of Ru(bpy)32+-poly(sulfosalicylic acid)/GCE. AB - A novel solid-state electrochemiluminescence (ECL) quenching sensor was constructed for determination of brilliant blue FCF (BB FCF). Under a simple electropolymerization step, poly(sulfosalicylic acid) (PSSA) film attached luminophore Ru(bpy)32+ was successfully formed on the surface of a glass carbon electrode [Ru(bpy)32+-PSSA/GCE], which exhibited excellent ECL behavior. A high quenching effect on the ECL signal of the Ru(bpy)32+-PSSA/GCE was obtained with the presence of low concentration of BB FCF. Moreover, the quenched ECL intensity showed a linear relation within the BB FCF concentration range of 0.5 - 7 and 7 - 10 MUmol/L, with a detection limit of 57 nmol/L (S/N = 3). Besides, Ru(bpy)32+ PSSA/GCE exhibited good reproducibility and was successfully applied in the practical detection of BB FCF in peppermint candy samples. PMID- 28993587 TI - Determination of Three Organochlorine Pesticides in Aqueous Samples by Solid Phase Extraction Based on Natural Nano Diatomite in Packed Syringe Coupled to Gas Chromatography-Mass Spectrometry. AB - A rapid, simple, and sensitive technique is proposed based on a miniaturized solid-phase extraction method named mictroextraction in a packed syringe coupled with gas chromatography-mass spectrometry for the preconcentration and determination of three organochlorine pesticides. These include hexachlorobenzene, heptachlor and aldrine in aqueous samples. For the first time, the natural nano diatomite is used a sorbent. Based on this technique, 6.0 mg of the nano sorbent is inserted in a syringe between two polypropylene frits. The analytes would be adsorbed on the solid phase, and would subsequently be eluted using organic solvents. The influence of some important parameters, such as the solution pH, type and volume of the organic desorption solvent, and amount of sorbent on the extraction efficiency of the selected pesticides, is investigated. The proposed method shows good linearity in the range of 0.1 - 40.0 MUg L-1, and at low limits of detection in the range of 0.02 - 0.13 MUg L-1 using the selected ion-monitoring mode. The reproducibility of this method was found to be in the range of 3.5 - 11.1% for the understudied pesticides. In order to evaluate the matrix effect, the developed method is also applied to the preconcentration and determination of the selected pesticides in different water samples. PMID- 28993588 TI - Multi-coloration of Calixarene-coated Silver Nanoparticles for the Visual Discrimination of Metal Elements. AB - Upon mixing with metal ions such as CdII, TbIII, CuII, NiII, PbII, ZnII, and CoII at pH 10.0, solutions of silver nanoparticles (AgNPs) coated with calix[4]arene-p tetrasulfonate (CAS-AgNP) exhibited multi-coloration from yellow to orange, violet, and green, depending on the metal elements present, which allowed for visual discrimination of the ions. This is contrary to the AgNP sensors exhibiting a uniform color change from yellow to red upon binding of a receptor molecules at the surface of AgNPs to an analyte. The TEM images of the samples obtained from the resultant solution showed two regions. First, a region where CAS-AgNPs assembled on the surface of the metal hydroxides. The size of the hydroxide crystals varied from 50 to 200 nm with the type of metal element present, and roughly correlated with the extinction band of the aggregated AgNPs. Second, the amorphous region in which CAS-AgNPs dispersed randomly. The difference in the amount of the crystal region and the area seemed to lead to the multi-coloration. PMID- 28993589 TI - Moment Analysis Theory for Size Exclusion Capillary Electrochromatography with Chemical Reaction of Intermolecular Interaction. AB - New moment equations were developed for size exclusion capillary electrochromatography (SECEC), in which intermolecular chemical reactions simultaneously took place. They explain how the first absolute and second central moments of elution peaks are correlated with some fundamental equilibrium and kinetic parameters of mass transfer and chemical reaction in SECEC column. In order to demonstrate the effectiveness of the moment equations, they were used to predict chromatographic behavior under hypothetical SECEC conditions. It was quantitatively studied how the association and dissociation rate constants of intermolecular interaction affected the position and spreading of elution peaks. It was indicated that both the intermolecular reaction kinetics and axial dispersion of solute molecules in a capillary column had a predominant contribution to the band broadening. PMID- 28993590 TI - An Electrochemical DNA Biosensor Based on Au-reduced Graphene Oxide Nanocomposite for Transgenic Event Bt63 Detection. AB - A simple and reliable electrochemical biosensor based on an in situ synthetic Au reduced graphene oxide (Au-RGO) nanocomposite was constructed in this work, which is considered to be a potential sensing platform for sensitive and selective Bt63 rice detection. UV-vis spectroscopy, transmission electron microscopy (TEM), and cyclic voltammograms of the surface characterization indicated that RGO was prepared successfully and Au nanoparticles were well dispersed on its surface with an average size of 20 nm. The square-wave voltammetry (SWV) response of the electrochemical marker methylene blue (MB) was chosen to monitor the probe immobilization and target hybridization event. Under the optimum conditions, the peak values of MB were linear with the logarithm of the target DNA concentrations being from 1.0 * 10-9 to 1.0 * 10-14 M; the detection limit was 3.36 * 10-15 M. Studies also demonstrated that the DNA biosensor had high reproducibility and stability. At last, we used this biosensor to detect several rice samples; it showed good sensitivity and selectivity. Thus the applicability of the method as an effective tool for genetically modified organism (GMO) quantification was confirmed by its accurate and sensitive results in Bt63 rice screening. PMID- 28993591 TI - Cool Mist Scavenging of Gas-Phase Molecules. AB - The purpose of analytical extractions is to simplify sample matrix without losing analyte molecules. Here we present a technique of extracting volatile compounds by scavenging gas-phase molecules with tiny liquid droplets (<10 MUm). A cool mist of the extracting solvent is generated by an ultrasonic transducer, transferred to the headspace of the sample chamber under atmospheric conditions, and pushed by a small pressure difference toward a condenser. By slowly passing over the sample, the microdroplets extract volatile species present in the sample headspace, and they coalesce in a cooled zone. The condensed liquid is collected for analysis by direct infusion mass spectrometry or chromatography coupled with mass spectrometry. Due to the high surface-to-volume ratio of the microdroplets, the mist depletes a great share of the volatile organics present in the headspace. Other advantages of cool mist scavenging include: selective extraction of gas-phase molecules, the extracting solvent can be miscible with the sample solvent, simplicity, high speed, and no requirement for heating that could potentially decompose the sample. In this study, cool mist scavenging was first tested on artificial samples containing esters. The relationship between the sample concentration and the extract concentration was verified theoretically and experimentally. Some of the possible confounding effects were tested and discussed. The technique was subsequently applied to qualitative analysis of selected complex samples in liquid and solid phase as well as an esterification reaction. PMID- 28993592 TI - Rhodol-derived Colorimetric and Fluorescent Probe with the Receptor of Carbonothioate for the Specific Detection of Mercury Ions. AB - Developing some methods that can simply and effectively detect mercury ions (Hg2+) in the environment and biological systems are very important due to the problems of high toxicity and biological accumulation. Herein, we report a simple rhodol-derived colorimetric and fluorescent probe rhodol-Hg with a recognition receptor of carbonothioate for the specific determination of Hg2+. The color of probe rhodol-Hg solution changed remarkably from colorless to pink in the presence of Hg2+, thus rhodol-Hg could act as a "naked-eye" probe for Hg2+. Additionally, this probe exhibited high selectivity and ultrasensitivity in aqueous solution with the limit of detection (LOD) of 1.4 nM toward Hg2+, and the linear range was 0 - 0.8 MUM determined by turn-on fluorescence spectrometry. Importantly, this probe has been successfully used for the detection of Hg2+ in environmental waters and living cells. PMID- 28993593 TI - A Newly Designed Solid-Phase Extraction-type Collection Device for Precise Determination of Polycyclic Aromatic Hydrocarbons in Air. AB - A newly designed styrene-divinylbenzene copolymer adsorbent packed solid-phase extraction (SPE)-type collection device for the quantitative determination of airborne polycyclic aromatic hydrocarbons (PAHs) containing two to five rings is reported in this manuscript. This SPE-type collection device offers rapid, easy and quantitative elution of the analytes and easier reuse. A small collection device was initially developed for investigating the basic collection and elution performances of the adsorbent with respect to PAHs. The analytes were quantitatively collected on the adsorbent up to 3 m3 of air sampling at a sampling temperature of 35 degrees C. The collected analytes were then completely eluted from the adsorbent by passing 3 mL of dichloromethane without carry-over of the analyte. During air collection, because no moisture was trapped on the adsorbent, the subsequent gas chromatography-mass spectrometric analysis was not influenced by moisture. Based on these successful performances, a wide-bore collection device was introduced for collecting larger air samples. After a quantitative investigation of the collection and elution performances of the wide bore collection device, it device was successfully applied for precise determinations of PAHs in atmospheric air. Further application and employment of the device for the precise determination of semi-volatile organic compounds in environmental air samples is expected due to these excellent results. PMID- 28993594 TI - Study on the Interaction between Rhodamine Dyes and Allura Red Based on Fluorescence Spectra and Its Analytical Application in Soft Drinks. AB - Allura red (AR) is a common food additive. It is of significance to detect AR sensitively and selectively in soft drinks. In this report, fluorescence spectra of allura red-rhodamine dyes systems were studied. In a pH 6.0 Britton-Robinson buffer medium, the fluorescence of rhodamine dyes, such as rhodamine B (RB), butylrhodamine B (BRB) and rhodamine 6G (R6G), can be quenched by AR. Impressively, the emission spectrums of the RB and BRB change slightly upon the addition of AR, but it was clear that the emission of R6G decreased dramatically in the presence of AR. Thus, we have succeeded in planning an improved method for specifically detecting AR on the basis of hydrophobic forces and the electrostatic attraction between R6G and AR. The results show that AR could combine with R6G to form an ion-association complex, which causes quenching of the emission intensity of R6G and changes of the UV-visible spectra. In this system, 0.097 - 6.0 MUmol L-1 AR could be simply detected owing to the decreased fluorescence of R6G in soft drinks, with a detection limit of 0.029 MUmol L-1. In addition, we also optimized the reaction conditions and evaluated the effects of some coexisting substances. According to the fluorescence decay time, the UV visible absorption spectra and the Stern-Volmer plots, the fluorescence quenching of R6G by AR is a static quenching process. PMID- 28993595 TI - Optimization of Analytical Conditions for a Rapid Determination of Aniline in Environmental Water by Liquid Chromatography/Tandem Mass Spectrometry. AB - A rapid determination of aniline in environmental water was examined based on liquid chromatography/tandem mass spectrometry (LC/MS/MS). Environmental water samples were diluted 20-fold with Mill-Q water and measured by LC/MS/MS after adding a surrogate substance (aniline-d5). In the results of the present study, the calibration curve of aniline showed good linearity in the range of 0.05 - 2.0 MUg/L. Since the RSD (repeatability) by measuring repeatedly an aniline standard solution (0.05 MUg/L, n = 7) was 3.2%, the repeatability of this work was very excellent. In addition, the recovery rate of aniline in environmental water was in the range of 99.0 - 102% with RSD 3.4 - 7.7%, and very good recovery test results were obtained. From these results, this analytical method was confirmed to be effective for aniline measurements of environmental water samples. Also, it is possible to conduct rapid analyses of aniline in environmental water without any solid-phase extraction process, compared to the solid-phase extraction-GC/MS method. PMID- 28993596 TI - Polycrystalline Boron-doped Diamond Electrolyte-solution-gate Field-effect Transistor Applied to the Measurement of Water Percentage in Ethanol. AB - A polycrystalline diamond electrolyte-solution-gate field-effect transistor (BDD SGFET) was successfully applied to the analysis of water content in ethanol. Due to the use of a no-gate-insulator FET, the developed sensor showed a four-times faster response than the conventional Si-FET, and a ten-times-faster response than a glass electrode. The output voltage showed good linearity with respect to the water content. This result is of practical importance because the traditional water content measurement methods are impractical due to their slow response. PMID- 28993597 TI - Using Laser Interference Lithography in the Fabrication of a Simplified Micro- and Nanofluidic Device for Label-free Detection. AB - Recently, we developed a label-free detection method based on optical diffraction, and implemented it in on our fabricated micro- and nanofluidic device. This detection method is simple and useful for detecting biomolecules, but the device fabrication consists of complicated processes. In this paper, we propose a simple method for fabricating the micro- and nanofluidic device; the fabrication combines laser interference lithography with conventional photolithography. The performance of a device fabricated by the proposed method is comparable to the performance of the device in our previous study. PMID- 28993599 TI - Circulating gonadotropins and testicular hormones during sexual maturation and annual changes in male bottlenose dolphins (Tursiops truncatus). AB - To reveal the reproductive biology in male bottlenose dolphins (Tursiops truncatus), circulating gonadotropins (follicle stimulating hormone [FSH] and luteinizing hormone [LH]) and testicular hormones (testosterone and inhibin) were monitored for 8-12 years in 2 captive bottlenose dolphins (Mars and Regulus). During the study period, Mars was undergoing sexual maturation, whereas Regulus was already mature at the beginning of the study. Assuming that Mars had reached sexual maturity when the significant increase in circulating testosterone levels was observed, serum concentration of inhibin was higher in the sexually immature stage than in the mature stage, whereas the serum concentration of FSH was higher in the sexually mature stage than in the immature stage. No difference was observed in the LH levels between pre- and post-sexual maturation. There was a significant increase in serum concentration of testosterone during spring in both animals. These results suggest that the mechanism responsible for regulating FSH secretion by inhibin functions during the sexually immature stage in this species. PMID- 28993600 TI - Triple-phase helical computed tomography in dogs with solid splenic masses. AB - We investigated the utility of triple-phase helical computed tomography (CT) in differentiating between benign and malignant splenic masses in dogs. Forty-two dogs with primary splenic masses underwent triple-phase helical CT scanning (before administration of contrast, and in the arterial phase, portal venous phase, and delayed phase) prior to splenectomy. Tissue specimens were sent for pathological diagnosis; these included hematomas (n=14), nodular hyperplasias (n=12), hemangiosarcomas (n=11), and undifferentiated sarcomas (n=5). The CT findings were compared with the histological findings. Nodular hyperplasia significantly displayed a homogeneous normal enhancement pattern in all phases. Hemangiosarcoma displayed 2 significant contrast-enhancement patterns, including a homogeneous pattern of poor enhancement in all phases, and a heterogeneous remarkable enhancement pattern in the arterial and portal venous phases. Hematoma and undifferentiated sarcoma displayed a heterogeneous normal enhancement pattern in all phases. The contrast-enhanced volumetric ratios of hematoma tended to be greater than those of undifferentiated sarcoma. Our study demonstrated that the characteristic findings on triple-phase helical CT could be useful for the preoperative differentiation of hematoma, nodular hyperplasia, hemangiosarcoma, and undifferentiated sarcoma in dogs. Triple-phase helical CT may be a useful diagnostic tool in dogs with splenic masses. PMID- 28993601 TI - Potency of an inactivated influenza vaccine prepared from A/duck/Hokkaido/162/2013 (H2N1) against a challenge with A/swine/Missouri/2124514/2006 (H2N3) in mice. AB - H2N2 influenza virus caused a pandemic starting in 1957 but has not been detected in humans since 1968. Thus, most people are immunologically naive to viruses of the H2 subtype. In contrast, H2 influenza viruses are continually isolated from wild birds, and H2N3 viruses were isolated from pigs in 2006. H2 influenza viruses could cause a pandemic if re-introduced into humans. In the present study, a vaccine against H2 influenza was prepared as an effective control measure against a future human pandemic. A/duck/Hokkaido/162/2013 (H2N1), which showed broad antigenic cross-reactivity, was selected from the candidate H2 influenza viruses recently isolated from wild birds in Asian countries. Sufficient neutralizing antibodies against homologous and heterologous viruses were induced in mice after two subcutaneous injections of the inactivated whole virus particle vaccine. The inactivated vaccine induced protective immunity sufficient to reduce the impact of challenges with A/swine/Missouri/2124514/2006 (H2N3). This study demonstrates that the inactivated whole virus particle vaccine prepared from an influenza virus library would be useful against a future H2 influenza pandemic. PMID- 28993602 TI - Triple-phase helical computed tomography of an arterio-hepatic venous shunt in a hepatic tumor in a dog. AB - A 10-year-old French bulldog presented with an abdominal tumor. Triple-phase helical computed tomography was performed, revealing a hepatic tumor, an enlarged hepatic lymph node, and no masses in other organs. The hepatic tumor demonstrated marked enhancement, similar to that of the aorta in the arterial phase. The tumor had rich vascularization and a hepatic arterio-venous shunt formed between the hepatic artery and middle hepatic vein. The hepatic tumor was surgically removed and histological diagnosis revealed a hepatic carcinoid tumor. During surgery, rapid massive arterial hemorrhage occurred from the site of the incision. The animal died without improvement post-surgery. In the case of an arterio-venous shunt in a hepatic tumor, it is important to be careful to avoid perioperative bleeding. PMID- 28993604 TI - Corrections. PMID- 28993603 TI - Comparison of Characteristics According to Reflux Type in Patients With Laryngopharyngeal Reflux. AB - OBJECTIVES: To analyze laryngopharyngeal reflux (LPR) as an acidic, nonacidic, or mixed type according to 24-hour multi-channel intraluminal impedance (MII) pH monitoring and the clinical characteristics of each type. METHODS: Ninety patients were prospectively enrolled in this study. All patients underwent 24 hour MII pH monitoring as a diagnostic tool. Eighty-three patients were diagnosed with LPR. The patients were classified into three groups according to the pH of the hypopharyngeal probe: the acid reflux group, nonacid reflux group, and mixed reflux group. Subjective symptoms and objective findings were evaluated based on patients' responses to the Short Form 12 Survey (SF-12), LPR health-related quality of life (LPR-HRQOL), reflux symptom index, and reflux finding score. RESULTS: The results of each group were compared. As a result, 34 patients were classified into the nonacid reflux group and 49 into the mixed reflux group. There were no patients classified as having acid reflux alone. There was no significant difference between the two groups when comparing the reflux symptom index, reflux finding score, LPR-HRQOL, or the mental component score of the SF 12. However, the physical component score of the SF-12 was higher in the nonacid reflux group (P=0.018). The DeMeester composite score (P=0.015) and total number of LPR events (P=0.001) were lower in the nonacid reflux group than in the mixed reflux group. CONCLUSION: In conclusion, no LPR patient had only acid reflux. The nonacid reflux LPR patients showed similar clinical characteristics and findings compared to the mixed reflux group, but exhibited significantly fewer LPR episodes. PMID- 28993605 TI - A Case of Diffuse Alveolar Hemorrhage as a Possible Complication of Bivalirudin Therapy. AB - BACKGROUND Diffuse alveolar hemorrhage (DAH) is a rare but potentially fatal complication of anticoagulant or antiplatelet therapy. Bivalirudin is a specific and reversible direct thrombin inhibitor (DTI). CASE REPORT We report a case of severe DAH, possibly related to bivalirudin use, in a 61-year-old patient undergoing coronary intervention. The patient had presented with an out-of hospital cardiac arrest due to acute ST elevation myocardial infarction (STEMI). During the coronary intervention, shortly after receiving bivalirudin, the patient started having frank bleeding from the endotracheal tube and developed hemodynamic compromise. Despite aggressive intervention and intensive care, the patient died. CONCLUSIONS At this time, to our knowledge, there have been no reports of DAH associated with the use of bivalirudin. PMID- 28993606 TI - External Validation of Survival-Predicting Models for Acute Myocardial Infarction with Extracorporeal Cardiopulmonary Resuscitation in a Chinese Single-Center Cohort. AB - BACKGROUND This study was designed as an external evaluation of potentially relevant models for acute myocardial infarction (AMI) with extracorporeal cardiopulmonary resuscitation (E-CPR). MATERIAL AND METHODS Twenty AMI adults that met criteria were retrospectively analyzed from January 2009 to January 2015. Six possible models - ENCOURAGE, SAVE, ECPR, GRACE, SHOCK, and a simplified risk chart - were identified by literature review and model scores calculated based on original data. Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment, commonly used in intensive care units, served as controls. A receiver operating characteristic curve was used to compare the models' discriminative power for predicting survival to discharge. RESULTS The ECPR model showed the best discriminative performance, with an area under the curve (AUC) of 0.893 (95% confidence interval [CI], 0.733-1.530, p=0.006); the cutoff was 12.5 points, with 66.7% sensitivity and 100% specificity. The "clinical" SHOCK model (including infarct site) showed weaker but still good discriminative power, with an AUC of 0.804 (95% CI, 0.580-1.027, p=0.035); the cutoff was 45.5 points, with 83.3% sensitivity and 71.4% specificity. The remaining models did not show significant discriminative power for predicting survival to discharge. Risk stratifications indicated that a statistically significant difference was observed in the distribution of patients into the ECPR group with different prognoses when stratified by its cutoff (p=0.003), while a trend of significant difference was shown when applied to the SHOCK model (p=0.05). CONCLUSIONS The ECPR and SHOCK models possess important abilities to predict intrahospital outcomes of AMI patients treated with E-CPR. PMID- 28993607 TI - Liver Transplantation for High Risk Hepatocellular Carcinoma After Liver Resection: A Sequential or Salvage Approach? AB - BACKGROUND Liver transplantation (LT) is the best radical treatment of hepatocellular carcinoma (HCC). Salvage liver transplantation (SalvLT) provides good outcomes for recurrent HCC cases after initial curative liver resection (LR). However, the salvage strategy is not feasible in all situations due to aggressive recurrences. Recently, sequential liver transplantation (SeqLT) was proposed for cases that show adverse pathological features after LR, thus LT is performed pre-emptively before recurrence. In this report, we compared the outcomes of SalvLT and SeqLT for surgical treatment of HCC. MATERIAL AND METHODS One hundred and ten cases underwent LR for HCC, then were subjected to either SalvLT (n=91) or SeqLT (n=19), from January 2001 to December 2015. For cases that underwent several LR before LT, we collected the data of the last LR before transplantation. A comparison was made according to pre- and post-transplant clinical and pathological variables. Survival analysis and comparison between both pathways are provided. RESULTS The median interval (months) between LR and LT for the SeqLT group and the SalvLT group were 9.6 and 22.2, respectively. (p=0.01). The LR histopathological features were similar in both groups. In the SalvLT group, the histopathological comparison between the criteria of last LR and the criteria of liver explants revealed that 14 cases advanced from stage I to stage II, one cases from stage I to stage IIIa, one case from stage I to stage IIIb, one case from stage I to stage IIIc, three cases from stage II to stage IIIb and one case from stage II to stage IIIc. The overall rate of pathological upstaging in the SalvLT group was 27%. The incidence of post-transplant HCC recurrence was 5% (1/19) and 11% (10/91) for the SeqLT and SalvLT groups, respectively (p=0.4). The incidence of post-LT in-hospital mortality was 0% among the SeqLT group and 2% (2/91) among the SalvLT group. The estimated rates of five year overall survival and cancer specific survival for the SeqLT group versus the SalvLT group were (92.3% versus 87.6%; p=0.4) and (92.3% versus 91.9%; p=0.7), respectively. CONCLUSIONS The SeqLT approach might be associated with low incidence of cancer recurrence, better overall survival, and less operative mortality. Another possible benefit is the avoidance of aggressive non transplantable HCC recurrences. More studies and/or randomization are required for highre evidence conclusions. PMID- 28993608 TI - Cascading effects of thermally-induced anemone bleaching on associated anemonefish hormonal stress response and reproduction. AB - Organisms can behaviorally, physiologically, and morphologically adjust to environmental variation via integrative hormonal mechanisms, ultimately allowing animals to cope with environmental change. The stress response to environmental and social changes commonly promotes survival at the expense of reproduction. However, despite climate change impacts on population declines and diversity loss, few studies have attributed hormonal stress responses, or their regulatory effects, to climate change in the wild. Here, we report hormonal and fitness responses of individual wild fish to a recent large-scale sea warming event that caused widespread bleaching on coral reefs. This 14-month monitoring study shows a strong correlation between anemone bleaching (zooxanthellae loss), anemonefish stress response, and reproductive hormones that decreased fecundity by 73%. These findings suggest that hormone stress responses play a crucial role in changes to population demography following climate change and plasticity in hormonal responsiveness may be a key mechanism enabling individual acclimation to climate change.Elevated temperatures can cause anemones to bleach, with unknown effects on their associated symbiotic fish. Here, Beldade and colleagues show that climate-induced bleaching alters anemonefish hormonal stress response, resulting in decreased reproductive hormones and severely impacted reproduction. PMID- 28993609 TI - Transcription factor Foxo1 is essential for IL-9 induction in T helper cells. AB - Interleukin 9 (IL-9)-producing helper T (Th9) cells have a crucial function in allergic inflammation, autoimmunity, immunity to extracellular pathogens and anti tumor immune responses. In addition to Th9, Th2, Th17 and Foxp3+ regulatory T (Treg) cells produce IL-9. A transcription factor that is critical for IL-9 induction in Th2, Th9 and Th17 cells has not been identified. Here we show that the forkhead family transcription factor Foxo1 is required for IL-9 induction in Th9 and Th17 cells. We further show that inhibition of AKT enhances IL-9 induction in Th9 cells while it reciprocally regulates IL-9 and IL-17 in Th17 cells via Foxo1. Mechanistically, Foxo1 binds and transactivates IL-9 and IRF4 promoters in Th9, Th17 and iTreg cells. Furthermore, loss of Foxo1 attenuates IL 9 in mouse and human Th9 and Th17 cells, and ameliorates allergic inflammation in asthma. Our findings thus identify that Foxo1 is essential for IL-9 induction in Th9 and Th17 cells.The transcription factor Foxo1 can control regulatory T cell and Th1 function. Here the authors show that Foxo1 is also critical for IL-9 production by Th9 cells and other IL-9-producing cells. PMID- 28993610 TI - Evolution of host adaptation in the Salmonella typhoid toxin. AB - The evolution of virulence traits is central for the emergence or re-emergence of microbial pathogens and for their adaptation to a specific host 1-5 . Typhoid toxin is an essential virulence factor of the human-adapted bacterial pathogen Salmonella Typhi 6,7 , the cause of typhoid fever in humans 8-12 . Typhoid toxin has a unique A2B5 architecture with two covalently linked enzymatic 'A' subunits, PltA and CdtB, associated with a homopentameric 'B' subunit made up of PltB, which has binding specificity for the N-acetylneuraminic acid (Neu5Ac) sialoglycans 6,13 prominently present in humans 14 . Here, we examine the functional and structural relationship between typhoid toxin and ArtAB, an evolutionarily related AB5 toxin encoded by the broad-host Salmonella Typhimurium 15 . We find that ArtA and ArtB, homologues of PltA and PltB, can form a functional complex with the typhoid toxin CdtB subunit after substitution of a single amino acid in ArtA, while ArtB can form a functional complex with wild type PltA and CdtB. We also found that, after addition of a single-terminal Cys residue, a CdtB homologue from cytolethal distending toxin can form a functional complex with ArtA and ArtB. In line with the broad host specificity of S. Typhimurium, we found that ArtB binds human glycans, terminated in N acetylneuraminic acid, as well as glycans terminated in N-glycolylneuraminic acid (Neu5Gc), which are expressed in most other mammals 14 . The atomic structure of ArtB bound to its receptor shows the presence of an additional glycan-binding site, which broadens its binding specificity. Despite equivalent toxicity in vitro, we found that the ArtB/PltA/CdtB chimaeric toxin exhibits reduced lethality in an animal model, indicating that the host specialization of typhoid toxin has optimized its targeting mechanisms to the human host. This is a remarkable example of a toxin evolving to broaden its enzymatic activities and adapt to a specific host. PMID- 28993611 TI - Natural product diversity associated with the nematode symbionts Photorhabdus and Xenorhabdus. AB - Xenorhabdus and Photorhabdus species dedicate a large amount of resources to the production of specialized metabolites derived from non-ribosomal peptide synthetase (NRPS) or polyketide synthase (PKS). Both bacteria undergo symbiosis with nematodes, which is followed by an insect pathogenic phase. So far, the molecular basis of this tripartite relationship and the exact roles that individual metabolites and metabolic pathways play have not been well understood. To close this gap, we have significantly expanded the database for comparative genomics studies in these bacteria. Clustering the genes encoded in the individual genomes into hierarchical orthologous groups reveals a high-resolution picture of functional evolution in this clade. It identifies groups of genes-many of which are involved in secondary metabolite production-that may account for the niche specificity of these bacteria. Photorhabdus and Xenorhabdus appear very similar at the DNA sequence level, which indicates their close evolutionary relationship. Yet, high-resolution mass spectrometry analyses reveal a huge chemical diversity in the two taxa. Molecular network reconstruction identified a large number of previously unidentified metabolite classes, including the xefoampeptides and tilivalline. Here, we apply genomic and metabolomic methods in a complementary manner to identify and elucidate additional classes of natural products. We also highlight the ability to rapidly and simultaneously identify potentially interesting bioactive products from NRPSs and PKSs, thereby augmenting the contribution of molecular biology techniques to the acceleration of natural product discovery. PMID- 28993613 TI - Consumers control carbon. PMID- 28993612 TI - An even pattern of xylan substitution is critical for interaction with cellulose in plant cell walls. AB - Xylan and cellulose are abundant polysaccharides in vascular plants and essential for secondary cell wall strength. Acetate or glucuronic acid decorations are exclusively found on even-numbered residues in most of the glucuronoxylan polymer. It has been proposed that this even-specific positioning of the decorations might permit docking of xylan onto the hydrophilic face of a cellulose microfibril 1-3 . Consequently, xylan adopts a flattened ribbon-like twofold screw conformation when bound to cellulose in the cell wall 4 . Here we show that ESKIMO1/XOAT1/TBL29, a xylan-specific O-acetyltransferase, is necessary for generation of the even pattern of acetyl esters on xylan in Arabidopsis. The reduced acetylation in the esk1 mutant deregulates the position-specific activity of the xylan glucuronosyltransferase GUX1, and so the even pattern of glucuronic acid on the xylan is lost. Solid-state NMR of intact cell walls shows that, without the even-patterned xylan decorations, xylan does not interact normally with cellulose fibrils. We conclude that the even pattern of xylan substitutions seen across vascular plants enables the interaction of xylan with hydrophilic faces of cellulose fibrils, and is essential for development of normal plant secondary cell walls. PMID- 28993614 TI - Mammal diversity influences the carbon cycle through trophic interactions in the Amazon. AB - Biodiversity affects many ecosystem functions and services, including carbon cycling and retention. While it is known that the efficiency of carbon capture and biomass production by ecological communities increases with species diversity, the role of vertebrate animals in the carbon cycle remains undocumented. Here, we use an extensive dataset collected in a high-diversity Amazonian system to parse out the relationship between animal and plant species richness, feeding interactions, tree biomass and carbon concentrations in soil. Mammal and tree species richness is positively related to tree biomass and carbon concentration in soil-and the relationship is mediated by organic remains produced by vertebrate feeding events. Our research advances knowledge of the links between biodiversity and carbon cycling and storage, supporting the view that whole community complexity-including vertebrate richness and trophic interactions-drives ecosystem function in tropical systems. Securing animal and plant diversity while protecting landscape integrity will contribute to soil nutrient content and carbon retention in the biosphere. PMID- 28993615 TI - Logic Synthesis of Recombinase-Based Genetic Circuits. AB - A synthetic approach to biology is a promising technique for various applications. Recent advancements have demonstrated the feasibility of constructing synthetic two-input logic gates in Escherichia coli cells with long term memory based on DNA inversion induced by recombinases. Moreover, recent evidences indicate that DNA inversion mediated by genome editing tools is possible. Powerful genome editing technologies, such as CRISPR-Cas9 systems, have great potential to be exploited to implement large-scale recombinase-based circuits. What remains unclear is how to construct arbitrary Boolean functions based on these emerging technologies. In this paper, we lay the theoretical foundation formalizing the connection between recombinase-based genetic circuits and Boolean functions. It enables systematic construction of any given Boolean function using recombinase-based logic gates. We further develop a methodology leveraging existing electronic design automation (EDA) tools to automate the synthesis of complex recombinase-based genetic circuits with respect to area and delay optimization. In silico experimental results demonstrate the applicability of our proposed methods as a useful tool for recombinase-based genetic circuit synthesis and optimization. PMID- 28993617 TI - A Bivariate Hypothesis Testing Approach for Mapping the Trait-Influential Gene. AB - The linkage disequilibrium (LD) based quantitative trait loci (QTL) model involves two indispensable hypothesis tests: the test of whether or not a QTL exists, and the test of the LD strength between the QTaL and the observed marker. The advantage of this two-test framework is to test whether there is an influential QTL around the observed marker instead of just having a QTL by random chance. There exist unsolved, open statistical questions about the inaccurate asymptotic distributions of the test statistics. We propose a bivariate null kernel (BNK) hypothesis testing method, which characterizes the joint distribution of the two test statistics in two-dimensional space. The power of this BNK approach is verified by three different simulation designs and one whole genome dataset. It solves a few challenging open statistical questions, closely separates the confounding between 'linkage' and 'QTL effect', makes a fine genome division, provides a comprehensive understanding of the entire genome, overcomes limitations of traditional QTL approaches, and connects traditional QTL mapping with the newest genotyping technologies. The proposed approach contributes to both the genetics literature and the statistics literature, and has a potential to be extended to broader fields where a bivariate test is needed. PMID- 28993616 TI - Bone corticalization requires local SOCS3 activity and is promoted by androgen action via interleukin-6. AB - Long bone strength is determined by its outer shell (cortical bone), which forms by coalescence of thin trabeculae at the metaphysis (corticalization), but the factors that control this process are unknown. Here we show that SOCS3-dependent cytokine expression regulates bone corticalization. Young male and female Dmp1Cre.Socs3 f/f mice, in which SOCS3 has been ablated in osteocytes, have high trabecular bone volume and poorly defined metaphyseal cortices. After puberty, male mice recover, but female corticalization is still impaired, leading to a lasting defect in bone strength. The phenotype depends on sex-steroid hormones: dihydrotestosterone treatment of gonadectomized female Dmp1Cre.Socs3 f/f mice restores normal cortical morphology, whereas in males, estradiol treatment, or IL 6 deletion, recapitulates the female phenotype. This suggests that androgen action promotes metaphyseal corticalization, at least in part, via IL-6 signaling.The strength of long bones is determined by coalescence of trabeculae during corticalization. Here the authors show that this process is regulated by SOCS3 via a mechanism dependent on IL-6 and expression of sex hormones. PMID- 28993618 TI - Mid-infrared dispersive wave generation in gas-filled photonic crystal fibre by transient ionization-driven changes in dispersion. AB - Gas-filled hollow-core photonic crystal fibre is being used to generate ever wider supercontinuum spectra, in particular via dispersive wave emission in the deep and vacuum ultraviolet, with a multitude of applications. Dispersive waves are the result of nonlinear transfer of energy from a self-compressed soliton, a process that relies crucially on phase-matching. It was recently predicted that, in the strong-field regime, the additional transient anomalous dispersion introduced by gas ionization would allow phase-matched dispersive wave generation in the mid-infrared-something that is forbidden in the absence of free electrons. Here we report the experimental observation of such mid-infrared dispersive waves, embedded in a 4.7-octave-wide supercontinuum that uniquely reaches simultaneously to the vacuum ultraviolet, with up to 1.7 W of total average power.Dispersive wave emission in gas-filled hollow-core photonic crystal fibres has been possible in the visible and ultraviolet via the optical Kerr effect. Here, Kottig et al. demonstrate dispersive waves generated by an additional transient anomalous dispersion from gas ionization in the mid-infrared. PMID- 28993619 TI - Enhanced nanochannel translocation and localization of genomic DNA molecules using three-dimensional nanofunnels. AB - The ability to precisely control the transport of single DNA molecules through a nanoscale channel is critical to DNA sequencing and mapping technologies that are currently under development. Here we show how the electrokinetically driven introduction of DNA molecules into a nanochannel is facilitated by incorporating a three-dimensional nanofunnel at the nanochannel entrance. Individual DNA molecules are imaged as they attempt to overcome the entropic barrier to nanochannel entry through nanofunnels with various shapes. Theoretical modeling of this behavior reveals the pushing and pulling forces that result in up to a 30 fold reduction in the threshold electric field needed to initiate nanochannel entry. In some cases, DNA molecules are stably trapped and axially positioned within a nanofunnel at sub-threshold electric field strengths, suggesting the utility of nanofunnels as force spectroscopy tools. These applications illustrate the benefit of finely tuning nanoscale conduit geometries, which can be designed using the theoretical model developed here.Forcing a DNA molecule into a nanoscale channel requires overcoming the free energy barrier associated with confinement. Here, the authors show that DNA injected through a funnel-shaped entrance more efficiently enters the nanochannel, thanks to facilitating forces generated by the nanofunnel geometry. PMID- 28993620 TI - D-Alanylation of teichoic acids contributes to Lactobacillus plantarum-mediated Drosophila growth during chronic undernutrition. AB - The microbial environment influences animal physiology. However, the underlying molecular mechanisms of such functional interactions are largely undefined. Previously, we showed that during chronic undernutrition, strains of Lactobacillus plantarum, a major commensal partner of Drosophila, promote host juvenile growth and maturation partly through enhanced expression of intestinal peptidases. By screening a transposon insertion library of Lactobacillus plantarum in gnotobiotic Drosophila larvae, we identify a bacterial cell-wall modifying machinery encoded by the pbpX2-dlt operon that is critical to enhance host digestive capabilities and promote animal growth and maturation. Deletion of this operon leads to bacterial cell wall alteration with a complete loss of D alanylation of teichoic acids. We show that L. plantarum cell walls bearing D alanylated teichoic acids are directly sensed by Drosophila enterocytes to ensure optimal intestinal peptidase expression and activity, juvenile growth and maturation during chronic undernutrition. We thus conclude that besides peptidoglycan, teichoic acid modifications participate in the host-commensal bacteria molecular dialogue occurring in the intestine. PMID- 28993622 TI - Evidence for mid-Holocene rice domestication in the Americas. AB - The development of agriculture is one of humankind's most pivotal achievements. Questions about plant domestication and the origins of agriculture have engaged scholars for well over a century, with implications for understanding its legacy on global subsistence strategies, plant distribution, population health and the global methane budget. Rice is one of the most important crops to be domesticated globally, with both Asia (Oryza sativa L.) and Africa (Oryza glaberrima Steud.) discussed as primary centres of domestication. However, until now the pre Columbian domestication of rice in the Americas has not been documented. Here we document the domestication of Oryza sp. wild rice by the mid-Holocene residents of the Monte Castelo shell mound starting at approximately 4,000 cal. yr BP, evidenced by increasingly larger rice husk phytoliths. Our data provide evidence for the domestication of wild rice in a region of the Amazon that was also probably the cradle of domestication of other major crops such as cassava (Manihot esculenta), peanut (Arachis hypogaea) and chilli pepper (Capsicum sp.). These results underline the role of wetlands as prime habitats for plant domestication worldwide. PMID- 28993621 TI - Structural basis for IL-1alpha recognition by a modified DNA aptamer that specifically inhibits IL-1alpha signaling. AB - IL-1alpha is an essential cytokine that contributes to inflammatory responses and is implicated in various forms of pathogenesis and cancer. Here we report a naphthyl modified DNA aptamer that specifically binds IL-1alpha and inhibits its signaling pathway. By solving the crystal structure of the IL-1alpha/aptamer, we provide a high-resolution structure of this critical cytokine and we reveal its functional interaction interface with high-affinity ligands. The non-helical aptamer, which represents a highly compact nucleic acid structure, contains a wealth of new conformational features, including an unknown form of G-quadruplex. The IL-1alpha/aptamer interface is composed of unusual polar and hydrophobic elements, along with an elaborate hydrogen bonding network that is mediated by sodium ion. IL-1alpha uses the same interface to interact with both the aptamer and its cognate receptor IL-1RI, thereby suggesting a novel route to immunomodulatory therapeutics.The cytokine interleukin 1alpha (IL-1alpha) plays an important role in inflammatory processes. Here the authors use SELEX to generate a modified DNA aptamer which specifically binds IL-1alpha, present the structure of the IL-1alpha/aptamer complex and show that this aptamer inhibits the IL-1alpha signaling pathway. PMID- 28993623 TI - Barriers and facilitators of effective self-management in asthma: systematic review and thematic synthesis of patient and healthcare professional views. AB - Self-management is an established, effective approach to controlling asthma, recommended in guidelines. However, promotion, uptake and use among patients and health-care professionals remain low. Many barriers and facilitators to effective self-management have been reported, and views and beliefs of patients and health care professionals have been explored in qualitative studies. We conducted a systematic review and thematic synthesis of qualitative research into self management in patients, carers and health care professionals regarding self management of asthma, to identify perceived barriers and facilitators associated with reduced effectiveness of asthma self-management interventions. Electronic databases and guidelines were searched systematically for qualitative literature that explored factors relevant to facilitators and barriers to uptake, adherence, or outcomes of self-management in patients with asthma. Thematic synthesis of the 56 included studies identified 11 themes: (1) partnership between patient and health care professional; (2) issues around medication; (3) education about asthma and its management; (4) health beliefs; (5) self-management interventions; (6) co-morbidities (7) mood disorders and anxiety; (8) social support; (9) non pharmacological methods; (10) access to healthcare; (11) professional factors. From this, perceived barriers and facilitators were identified at the level of individuals with asthma (and carers), and health-care professionals. Future work addressing the concerns and beliefs of adults, adolescents and children (and carers) with asthma, effective communication and partnership, tailored support and education (including for ethnic minorities and at risk groups), and telehealthcare may improve how self-management is recommended by professionals and used by patients. Ultimately, this may achieve better outcomes for people with asthma. PMID- 28993625 TI - The mystery of life beyond menopause. PMID- 28993624 TI - Structure of the calcium-dependent type 2 secretion pseudopilus. AB - Many Gram-negative bacteria use type 2 secretion systems (T2SSs) to secrete proteins involved in virulence and adaptation. Transport of folded proteins via T2SS nanomachines requires the assembly of inner membrane-anchored fibres called pseudopili. Although efficient pseudopilus assembly is essential for protein secretion, structure-based functional analyses are required to unravel the mechanistic link between these processes. Here, we report an atomic model for a T2SS pseudopilus from Klebsiella oxytoca, obtained by fitting the NMR structure of its calcium-bound subunit PulG into the ~5-A-resolution cryo-electron microscopy reconstruction of assembled fibres. This structure reveals the comprehensive network of inter-subunit contacts and unexpected features, including a disordered central region of the PulG helical stem, and highly flexible C-terminal residues on the fibre surface. NMR, mutagenesis and functional analyses highlight the key role of calcium in PulG folding and stability. Fibre disassembly in the absence of calcium provides a basis for pseudopilus length control, essential for protein secretion, and supports the Archimedes screw model for the type 2 secretion mechanism. PMID- 28993626 TI - The application of thermophilic DNA primase TtDnaG2 to DNA amplification. AB - For DNA replication in vivo, DNA primase uses a complementary single-stranded DNA template to synthesize RNA primers ranging from 4 to 20 nucleotides in length, which are then elongated by DNA polymerase. Here, we report that, in the presence of double-stranded DNA, the thermophilic DNA primase TtDnaG2 synthesizes RNA primers of around 100 nucleotides with low initiation specificity at 70 degrees C. Analysing the structure of TtDnaG2, we identified that it adopts a compact conformation. The conserved sites in its zinc binding domain are sequestered away from its RNA polymerase domain, which might give rise to the low initiation specificity and synthesis of long RNA segments by TtDnaG2. Based on these unique features of TtDnaG2, a DNA amplification method has been developed. We utilized TtDnaG2 to synthesize RNA primers at 70 degrees C after 95 degrees C denaturation, followed by isothermal amplification with the DNA polymerase Bst3.0 or phi29. Using this method, we successfully amplified genomic DNA of a virus with 100% coverage and low copy number variation. Our data also demonstrate that this method can efficiently amplify circular DNA from a mixture of circular DNA and linear DNA, thus providing a tool to amplify low-copy-number circular DNA such as plasmids. PMID- 28993627 TI - High-performance MnO2-deposited graphene/activated carbon film electrodes for flexible solid-state supercapacitor. AB - High theoretical capacitance of MnO2 nanoparticles were successfully electrodeposited on the conductive graphene/activated carbon (GN/AC) composite film, and the urchin type MnO2 microspheres were controlled by adjusting the electro-deposition reaction times. The GN/AC/MnO2-1200s composite electrodes exhibited a maximum specific capacitance of 1231 mF/cm2 (MnO2 loading mass of 7.65 mg/cm2 and the mass specific capacitance of 123 F/g) at a current density of 0.5 mA/cm2. The assembled flexible solid-state symmetric supercapacitor had a good mechanical flexibility (about 88.6% of its original capacitance after 500 bending times) and prominent cycling stability (about 82.8% retention in capacitance over 10000 cycles). More importantly, the device could possess a maximum energy density of 0.27 mW h/cm3 and a maximum power density of 0.02 W/cm3. These results well demonstrate a great potential for applications of GN/AC/MnO2 composite electrodes in flexible energy storage devices. PMID- 28993628 TI - Oxidized g-C3N4/polyaniline nanofiber composite for the selective removal of hexavalent chromium. AB - Nanomaterials with selective adsorption properties are in demand for environmental applications. Herein, acid etching and oxidative decomposition of melon units of graphitic carbon nitride (g-C3N4) was performed to obtain the oxidized graphitic carbon nitride (Ox-g-C3N4) nanosheets. Ox- g-C3N4 nanosheets were further decorated on the polyaniline nanofiber (Ox-g-C3N4/Pani-NF). Ox-g C3N4/Pani-NF was well characterized and further applied for a selective removal of hexavalent chromium (Cr(VI)) form aqueous solution. The zeta potential analysis indicate that the surface of Ox-g-C3N4/Pani-NF was positively charged which could be beneficial to bind anionic Cr(VI) ions electrostatically. In addition, nitrogen and oxygen containing functional groups exist on the Ox-g C3N4/Pani-NF were mainly responsible for adsorption of Cr(VI) ions from aqueous solution. Moreover, the adsorption of Cr(VI) ions was also dependent on solution pH, reaction temperature and initial concentration of Cr(VI) ions. The maximum monolayer adsorption capacity of Ox-g-C3N4/Pani-NF for Cr(VI), calculated from Langmuir isotherm was 178.57 mg/g at pH = 2 and 30 degrees C. The activation energy (Ea = -20.66 kJ/mol) and the enthalpy change (DeltaH degrees = -22.055 kJ/mol) validate the role of physical forces in adsorption of Cr(VI). These results demonstrate that Ox-g-C3N4/Pani-NF can be used as a potential adsorbent for environmental remediation applications. PMID- 28993629 TI - Global trade statistics lack granularity to inform traceability and management of diverse and high-value fishes. AB - Illegal, unreported and unregulated (IUU) fishing and seafood supply chain fraud are multifaceted problems that demand multifaceted solutions. Here, we investigate the extent to which global fisheries trade data analyses can support effective seafood traceability and promote sustainable seafood markets using one of the world's most highly prized, yet misunderstood, groups of fishes as a model: the snappers, family Lutjanidae. By collating and comparing production, import and export data from international and national statistical collections for the period 2006-2013, we show that official trade data severely lack the level of detail required to track snapper trade flows, uncover potential IUU activities and/or inform exploitation management of snappers and related species. Moreover, we contend that the lack of taxonomic granularity and use of vague generic names in trade records represent one of the most insidious impediments to seafood traceability, and suggest that widely used harmonised commodity classification systems should evolve to address these gaps. PMID- 28993630 TI - alpha-Synuclein impairs ferritinophagy in the retinal pigment epithelium: Implications for retinal iron dyshomeostasis in Parkinson's disease. AB - Retinal degeneration is prominent in Parkinson's disease (PD), a neuromotor disorder associated with aggregation of alpha-synuclein (alpha-syn) in the substantia-nigra (SN). Although alpha-syn is expressed in the neuroretina, absence of prominent aggregates suggests altered function as the likely cause of retinal pathology. We demonstrate that alpha-syn impairs ferritinophagy, resulting in the accumulation of iron-rich ferritin in the outer retina in-vivo and retinal-pigment-epithelial (RPE) cells in-vitro. Over-expression of Rab1a restores ferritinophagy, suggesting that alpha-syn impairs lysosomal function by disrupting the trafficking of lysosomal hydrolases. Surprisingly, upregulation of ferritin in RPE cells by exogenous iron in-vitro stimulated the release of ferritin and alpha-syn in exosomes, suggesting that iron overload due to impaired ferritinophagy or other cause(s) is likely to initiate prion-like spread of alpha syn and ferritin, creating retinal iron dyshomeostasis and associated cytotoxicity. Since over-expression of alpha-syn is a known cause of PD, these results explain the likely cause of PD-associated retinal degeneration. PMID- 28993632 TI - Erratum: Laparoscopic versus opengastric surgery for the treatment of pathological T1N0M0 gastric cancer in elderly patients: a matched study. AB - A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper. PMID- 28993633 TI - Rabies virus modifies host behaviour through a snake-toxin like region of its glycoprotein that inhibits neurotransmitter receptors in the CNS. AB - Rabies virus induces drastic behaviour modifications in infected hosts. The mechanisms used to achieve these changes in the host are not known. The main finding of this study is that a region in the rabies virus glycoprotein, with homologies to snake toxins, has the ability to alter behaviour in animals through inhibition of nicotinic acetylcholine receptors present in the central nervous system. This finding provides a novel aspect to virus receptor interaction and host manipulation by pathogens in general. The neurotoxin-like region of the rabies virus glycoprotein inhibited acetylcholine responses of alpha4beta2 nicotinic receptors in vitro, as did full length ectodomain of the rabies virus glycoprotein. The same peptides significantly altered a nicotinic receptor induced behaviour in C. elegans and increased locomotor activity levels when injected into the central nervous system of mice. These results provide a mechanistic explanation for the behavioural changes in hosts infected by rabies virus. PMID- 28993631 TI - Establishment of a repeated social defeat stress model in female mice. AB - Numerous studies have employed repeated social defeat stress (RSDS) to study the neurobiological mechanisms of depression in rodents. An important limitation of RSDS studies to date is that they have been conducted exclusively in male mice due to the difficulty of initiating attack behavior directed toward female mice. Here, we establish a female mouse model of RSDS by inducing male aggression toward females through chemogenetic activation of the ventrolateral subdivision of the ventromedial hypothalamus (VMHvl). We demonstrate that females susceptible to RSDS display social avoidance, anxiety-like behavior, reduction of body weight, and elevated levels of circulating interleukin 6. In contrast, a subset of mice we term resilient only display anxiety-like behaviors after RSDS. This model allows for investigation of sex differences in the neurobiological mechanisms of defeat-induced depression-like behaviors. A robust female social defeat model is a critical first step in the identification and development of novel therapeutic compounds to treat depression and anxiety disorders in women. PMID- 28993634 TI - Changes in soil properties, X-ray-mineral diffractions and infrared-functional groups in bulk soil and fractions following afforestation of farmland, Northeast China. AB - Analysis of soil properties, the compositional traits in bulk soil and different fractions and their responses to afforestation practices may possibly facilitate clarification of the mechanisms underlying soil changes. Soil properties, the compositional functional groups and minerals were determined in the bulk soil and fractions from forests and adjacent farmlands. The afforestation of farmland could induce accumulation of soil organic carbon [SOC] (+18%) and nitrogen [N] (+4%) with pH increase (+4%), and declines in electric conductivity (-15%) and bulk density (-3%). Sand and aggregates [SA] and easily oxidized fraction [EO] mainly contributed to the SOC and N accumulation. Moreover, afforestation-induced changes were observed in O-H & N-H stretching (-26%), feldspar (+52%) and huntite crystallinity (-40%). The changes of soil properties were strongly associated with the changes in functional groups, followed by minerals. Of them, asymmetric COO- & C = O stretching & O-H bending, symmetric COO- stretching, huntite and smectite-vermiculite crystallinity were the key factors responsible for the changes of soil properties. Our findings highlight that degraded farmland afforestation could strongly affect soil properties in the bulk soil, and the changes in fractions (mainly SA and EO) as well as their changes in the compositional traits strongly supported these bulk soil changes. PMID- 28993635 TI - Response of human periodontal ligament stem cells to IFN-gamma and TLR-agonists. AB - Periodontal ligament stem cells similarly to the mesenchymal stem cells of other tissues possess immunomodulatory properties, which are regulated by different cytokines, particularly by interferon-gamma (IFN-gamma). In contrast, less information is provided about the effect of toll-like receptors ligand on immunomodulatory properties of these cells. In the present study we investigated the response of human periodontal ligament stem cells (hPDLSCs) in response to simultaneous stimulation with IFN-gamma and toll-like receptor (TLR) agonists. The resulting expression of indoleamine-2,3-dioxygenase-1 (IDO-1), interleukin (IL)-6, IL-8 and monocyte chemotactic protein 1 (MCP-1) was investigated. The expression of IDO-1 was upregulated by IFN-gamma in both gene and protein levels. TLR2 agonists Pam3CSK4 induced gene expression of IDO-1, but had no effect on protein expression. IFN-gamma induced IDO-1 protein expression was further enhanced by Pam3CSK4. TLR-4 agonist E. coli LPS has no significant effect on neither basal nor IFN-gamma induced IDO-1 protein expression. The production of IL-6, IL-8, and MCP-1 was induced by TLR agonists. Neither basal nor TLR agonists induced production of these proteins was affected by IFN-gamma. Our data shows potential interaction between IFN-gamma and TLR2 responses in hPDLSCs, which might be involved in regulation of immune response in inflammatory diseases, and particularly periodontitis. PMID- 28993636 TI - Involvement of PUF60 in Transcriptional and Post-transcriptional Regulation of Hepatitis B Virus Pregenomic RNA Expression. AB - Here we identified PUF60, a splicing factor and a U2 small nuclear ribonucleoprotein auxiliary factor, as a versatile regulator of transcriptional and post-transcriptional steps in expression of hepatitis B virus (HBV) 3.5 kb, precore plus pregenomic RNA. We demonstrate that PUF60 is involved in: 1) up regulation of core promoter activity through its interaction with transcription factor TCF7L2, 2) promotion of 3.5 kb RNA degradation and 3) suppression of 3.5 kb RNA splicing. When the 1.24-fold HBV genome was introduced into cells with the PUF60-expression plasmid, the 3.5 kb RNA level was higher at days 1-2 post transfection but declined thereafter in PUF60-expressing cells compared to viral replication control cells. Deletion analyses showed that the second and first RNA recognition motifs (RRMs) within PUF60 are responsible for core promoter activation and RNA degradation, respectively. Expression of PUF60 mutant deleting the first RRM led to higher HBV production. To our knowledge, this is the first to identify a host factor involved in not only positively regulating viral gene expression but also negative regulation of the same viral life cycle. Functional linkage between transcriptional and post-transcriptional controls during viral replication might be involved in mechanisms for intracellular antiviral defense and viral persistence. PMID- 28993638 TI - Pulsed sputtering epitaxial growth of m-plane InGaN lattice-matched to ZnO. AB - m-Plane GaN and InGaN films were grown on m-plane ZnO substrates at ~350 degrees C by pulsed sputtering deposition. It was found that the critical thickness of the m-plane GaN films grown on ZnO lies between 25 and 62 nm, whereas 180-nm thick m-plane In0.12Ga0.88N can be coherently grown on ZnO substrates, which is explained well by theoretical calculations based on an energy-balance model. The coherently grown m-plane InGaN on ZnO exhibited narrow X-ray rocking curves compared with the m-plane GaN grown on ZnO. These results demonstrate the benefit of lattice-matched ZnO substrates for epitaxy of high-quality nonpolar InGaN films. PMID- 28993637 TI - HTLV-1 bZIP factor suppresses TDP1 expression through inhibition of NRF-1 in adult T-cell leukemia. AB - Adult T-cell leukemia (ATL) is an aggressive T-cell malignancy caused by human T cell leukemia virus type 1 (HTLV-1). We recently reported that abacavir, an anti HIV-1 drug, potently and selectively kills ATL cells. This effect was attributed to the reduced expression of tyrosyl-DNA-phosphodiesterase 1 (TDP1), a DNA repair enzyme, in ATL cells. However, the molecular mechanism underlying the downregulation of TDP1 in ATL cells remains elusive. Here we identified the core promoter of the TDP1 gene, which contains a conserved nuclear respiratory factor 1 (NRF-1) binding site. Overexpression of NRF-1 increased TDP1-promoter activity, whereas the introduction of dominant-negative NRF-1 repressed such activity. Overexpression of NRF-1 also upregulated endogenous TDP-1 expression, while introduction of shNRF-1 suppressed TDP1 in Jurkat T cells, making them susceptible to abacavir. These results indicate that NRF-1 is a positive transcriptional regulator of TDP1-gene expression. Importantly, we revealed that HTLV-1 bZIP factor (HBZ) protein which is expressed in all ATL cases physically interacts with NRF-1 and inhibits the DNA-binding ability of NRF-1. Taken together, HBZ suppresses TDP1 expression by inhibiting NRF-1 function in ATL cells. The HBZ/NRF-1/TDP1 axis provides new therapeutic targets against ATL and might explain genomic instability leading to the pathogenesis of ATL. PMID- 28993639 TI - Evaluation of water quality based on a machine learning algorithm and water quality index for the Ebinur Lake Watershed, China. AB - The water quality index (WQI) has been used to identify threats to water quality and to support better water resource management. This study combines a machine learning algorithm, WQI, and remote sensing spectral indices (difference index, DI; ratio index, RI; and normalized difference index, NDI) through fractional derivatives methods and in turn establishes a model for estimating and assessing the WQI. The results show that the calculated WQI values range between 56.61 and 2,886.51. We also explore the relationship between reflectance data and the WQI. The number of bands with correlation coefficients passing a significance test at 0.01 first increases and then decreases with a peak appearing after 1.6 orders. WQI and DI as well as RI and NDI correlation coefficients between optimal band combinations of the peak also appear after 1.6 orders with R2 values of 0.92, 0.58 and 0.92. Finally, 22 WQI estimation models were established by POS-SVR to compare the predictive effects of these models. The models based on a spectral index of 1.6 were found to perform much better than the others, with an R2 of 0.92, an RMSE of 58.4, and an RPD of 2.81 and a slope of curve fitting of 0.97. PMID- 28993640 TI - Reconstruction of non-error magnetic hologram data by magnetic assist recording. AB - Hologram memory is expected to be the next-generation of optical data storage technology. Bismuth-substituted yttrium iron garnet is typically used for rewritable magnetic hologram media. The diffraction efficiency of magnetic holography depends on the Faraday rotation angle, but the experimental diffraction efficiency is not as high as that expected from calculations. This difference could be caused by incomplete magnetization reversal at the recorded region. In this study, we investigated the effects of magnetic assist (MA) recording through numerical simulation and experiment to improve the diffraction efficiency and the resulting reconstructed images. The improvement of diffraction efficiency was more effective in garnet films thinner than the width of a fringe, and a suitable value of the assist magnetic field was identified for the improvement. In addition, MA recording improved the intensity of reconstructed images and broadened the non-error recording conditions to the low energy region. This technique shows promise in improving the reconstructed quality of magnetic hologram data. PMID- 28993641 TI - Revealing hidden complexities of genomic rearrangements generated with Cas9. AB - Modelling human diseases caused by large genomic rearrangements has become more accessible since the utilization of CRISPR/Cas9 in mammalian systems. In a previous study, we showed that genomic rearrangements of up to one million base pairs can be generated by direct injection of CRISPR/Cas9 reagents into mouse zygotes. Although these rearrangements are ascertained by junction PCR, we describe here a variety of anticipated structural changes often involving reintegration of the region demarcated by the gRNAs in the vicinity of the edited locus. We illustrate here some of this diversity detected by high-resolution fibre-FISH and conclude that extensive molecular analysis is required to fully understand the structure of engineered chromosomes generated by Cas9. PMID- 28993642 TI - Evidence for in-gap surface states on the single phase SmB6(001) surface. AB - Structural and electronic properties of the SmB6(001) single-crystal surface prepared by Ar+ ion sputtering and controlled annealing are investigated by scanning tunneling microscopy. In contrast to the cases of cleaved surfaces, we observe a single phase surface with a non-reconstructed p(1 * 1) lattice on the entire surface at an optimized annealing temperature. The surface is identified as Sm-terminated on the basis of spectroscopic measurements. On a structurally uniform surface, the emergence of the in-gap state, a robust surface state against structural variation, is further confirmed inside a Kondo hybridization gap at 4.4 K by temperature and atomically-resolved spatial dependences of the differential conductance spectrum near the Fermi energy. PMID- 28993643 TI - A sexually dimorphic pre-stressed translational signature in CA3 pyramidal neurons of BDNF Val66Met mice. AB - Males and females use distinct brain circuits to cope with similar challenges. Using RNA sequencing of ribosome-bound mRNA from hippocampal CA3 neurons, we found remarkable sex differences and discovered that female mice displayed greater gene expression activation after acute stress than males. Stress sensitive BDNF Val66Met mice of both sexes show a pre-stressed translational phenotype in which the same genes that are activated without applied stress are also induced in wild-type mice by an acute stressor. Behaviourally, only heterozygous BDNF Val66Met females exhibit spatial memory impairment, regardless of acute stress. Interestingly, this effect is not observed in ovariectomized heterozygous BDNF Val66Met females, suggesting that circulating ovarian hormones induce cognitive impairment in Met carriers. Cognitive deficits are not observed in males of either genotype. Thus, in a brain region not normally associated with sex differences, this work sheds light on ways that genes, environment and sex interact to affect the transcriptome's response to a stressor.Animals' response to acute stress is known to be influenced by sex and genetics. Here the authors performed RNA-seq on actively translated mRNAs in hippocampal CA3 neurons in mice, and document the effects of sex and genotype (i.e., BDNF Val66Met) on acute stress-induced gene expression. PMID- 28993645 TI - The Impact of parasitic loss on solar cells with plasmonic nano-textured rear reflectors. AB - Significant photocurrent enhancement has been demonstrated using plasmonic light trapping structures comprising nanostructured metallic features at the rear of the cell. These structures have conversely been identified as suffering heightened parasitic absorption into the metal at certain resonant wavelengths severely mitigating benefits of light trapping. In this study, we undertook simulations exploring the relationship between enhanced absorption into the solar cell, and parasitic losses in the metal. These simulations reveal that resonant wavelengths associated with high parasitic losses in the metal could also be associated with high absorption enhancement in the solar cell. We identify mechanisms linking these parasitic losses and absorption enhancements, but found that by ensuring correct design, the light trapping structures will have a positive impact on the overall solar cell performance. Our results clearly show that the large angle scattering provided by the plasmonic nanostructures is the reason for the enhanced absorption observed in the solar cells. PMID- 28993644 TI - Membrane Trafficking Modulation during Entamoeba Encystation. AB - Entamoeba histolytica is an intestinal parasite that infects 50-100 million people and causes up to 55,000 deaths annually. The transmissive form of E. histolytica is the cyst, with a single infected individual passing up to 45 million cysts per day, making cyst production an attractive target for infection control. Lectins and chitin are secreted to form the cyst wall, although little is known about the underlying membrane trafficking processes supporting encystation. As E. histolytica does not readily form cysts in vitro, we assessed membrane trafficking gene expression during encystation in the closely related model Entamoeba invadens. Genes involved in secretion are up-regulated during cyst formation, as are some trans-Golgi network-to-endosome trafficking genes. Furthermore, endocytic and general trafficking genes are up-regulated in the mature cyst, potentially preserved as mRNA in preparation for excystation. Two divergent dynamin-related proteins found in Entamoeba are predominantly expressed during cyst formation. Phylogenetic analyses indicate that they are paralogous to, but quite distinct from, classical dynamins found in human, suggesting that they may be potential drug targets to block encystation. The membrane-trafficking machinery is clearly regulated during encystation, providing an additional facet to understanding this crucial parasitic process. PMID- 28993646 TI - LSD1 protects against hippocampal and cortical neurodegeneration. AB - To investigate the mechanisms that maintain differentiated cells, here we inducibly delete the histone demethylase LSD1/KDM1A in adult mice. Loss of LSD1 leads to paralysis, along with widespread hippocampus and cortex neurodegeneration, and learning and memory defects. We focus on the hippocampus neuronal cell death, as well as the potential link between LSD1 and human neurodegenerative disease and find that loss of LSD1 induces transcription changes in common neurodegeneration pathways, along with the re-activation of stem cell genes, in the degenerating hippocampus. These data implicate LSD1 in the prevention of neurodegeneration via the inhibition of inappropriate transcription. Surprisingly, we also find that transcriptional changes in the hippocampus are similar to Alzheimer's disease (AD) and frontotemporal dementia (FTD) cases, and LSD1 is specifically mislocalized to pathological protein aggregates in these cases. These data raise the possibility that pathological aggregation could compromise the function of LSD1 in AD and FTD."LSD1 is a histone demethylase that plays many roles during development. Here, the authors provide evidence that loss of LSD1 in adult mice leads to paralysis and neurodegeneration in the hippocampus and cortex and suggest a potential link between LSD1 and human neurodegenerative disease. PMID- 28993647 TI - Usefulness of kidney slices for functional analysis of apical reabsorptive transporters. AB - Kidney plays a key role in the elimination and reabsorption of drugs and nutrients, however in vitro methods to evaluate renal disposition are limited. In the present study, we investigated usefulness of isolated kidney slice, which had been used for transport only at basolateral membrane of tubular epithelial cells, for evaluation of apical membrane transporters. As transporters that are easy to discriminate between apical and basolateral transports, apical membrane specific and sodium-dependent transporters (SGLTs and OCTNs) and pH-dependent transporters (PEPTs) are selected. Uptake of ergothioneine, carnitine and methyl-alpha-D glucopyranoside, which are substrates of apical Octn1, Octn2, and Sglt1/2, respectively, by mice kidney slices showed clear Na+ dependence and reduction by selective inhibitors. In addition, sodium dependence of ergothioneine uptake was negligible in the kidney slice from Octn1-gene deficient mice. Moreover, uptake of PepT1/2 substrate glycyl-sarcosine, was higher than that in the presence of glycyl-leucine, a non-specific Pept inhibitor. The K m and IC 50 values for substrates and inhibitors of each transporter were mostly comparable to those obtained in transporter-transfected cells. In conclusion, it was demonstrated that kidney slices are promising tool to study transporters expressed at the apical membranes as well as basolateral membranes of kidney tubular epithelial cells. PMID- 28993648 TI - Upstream watershed condition predicts rural children's health across 35 developing countries. AB - Diarrheal disease (DD) due to contaminated water is a major cause of child mortality globally. Forests and wetlands can provide ecosystem services that help maintain water quality. To understand the connections between land cover and childhood DD, we compiled a database of 293,362 children in 35 countries with information on health, socioeconomic factors, climate, and watershed condition. Using hierarchical models, here we find that higher upstream tree cover is associated with lower probability of DD downstream. This effect is significant for rural households but not for urban households, suggesting differing dependence on watershed conditions. In rural areas, the effect of a 30% increase in upstream tree cover is similar to the effect of improved sanitation, but smaller than the effect of improved water source, wealth or education. We conclude that maintaining natural capital within watersheds can be an important public health investment, especially for populations with low levels of built capital.Globally diarrheal disease through contaminated water sources is a major cause of child mortality. Here, the authors compile a database of 293,362 children in 35 countries and find that upstream tree cover is linked to a lower probability of diarrheal disease and that increasing tree cover may lower mortality. PMID- 28993649 TI - A three-dimensional view of structural changes caused by deactivation of fluid catalytic cracking catalysts. AB - Since its commercial introduction three-quarters of a century ago, fluid catalytic cracking has been one of the most important conversion processes in the petroleum industry. In this process, porous composites composed of zeolite and clay crack the heavy fractions in crude oil into transportation fuel and petrochemical feedstocks. Yet, over time the catalytic activity of these composite particles decreases. Here, we report on ptychographic tomography, diffraction, and fluorescence tomography, as well as electron microscopy measurements, which elucidate the structural changes that lead to catalyst deactivation. In combination, these measurements reveal zeolite amorphization and distinct structural changes on the particle exterior as the driving forces behind catalyst deactivation. Amorphization of zeolites, in particular, close to the particle exterior, results in a reduction of catalytic capacity. A concretion of the outermost particle layer into a dense amorphous silica-alumina shell further reduces the mass transport to the active sites within the composite.Catalyst deactivation in fluid catalytic cracking processes is unavoidably associated with structural changes. Here, the authors visualize the deactivation of zeolite catalysts by ptychography and other imaging techniques, showing pronounced amorphization of the outer layer of the catalyst particles. PMID- 28993650 TI - Development of A Machine Learning Algorithm to Classify Drugs Of Unknown Fetal Effect. AB - Many drugs commonly prescribed during pregnancy lack a fetal safety recommendation - called FDA 'category C' drugs. This study aims to classify these drugs into harmful and safe categories using knowledge gained from chemoinformatics (i.e., pharmacological similarity with drugs of known fetal effect) and empirical data (i.e., derived from Electronic Health Records). Our fetal loss cohort contains 14,922 affected and 33,043 unaffected pregnancies and our congenital anomalies cohort contains 5,658 affected and 31,240 unaffected infants. We trained a random forest to classify drugs of unknown pregnancy class into harmful or safe categories, focusing on two distinct outcomes: fetal loss and congenital anomalies. Our models achieved an out-of-bag accuracy of 91% for fetal loss and 87% for congenital anomalies outperforming null models. Fifty seven 'category C' medications were classified as harmful for fetal loss and eleven for congenital anomalies. This includes medications with documented harmful effects, including naproxen, ibuprofen and rubella live vaccine. We also identified several novel drugs, e.g., haloperidol, that increased the risk of fetal loss. Our approach provides important information on the harmfulness of 'category C' drugs. This is needed, as no FDA recommendation exists for these drugs' fetal safety. PMID- 28993651 TI - Escape and surveillance asymmetries in locusts exposed to a Guinea fowl-mimicking robot predator. AB - Escape and surveillance responses to predators are lateralized in several vertebrate species. However, little is known on the laterality of escapes and predator surveillance in arthropods. In this study, we investigated the lateralization of escape and surveillance responses in young instars and adults of Locusta migratoria during biomimetic interactions with a robot-predator inspired to the Guinea fowl, Numida meleagris. Results showed individual-level lateralization in the jumping escape of locusts exposed to the robot-predator attack. The laterality of this response was higher in L. migratoria adults over young instars. Furthermore, population-level lateralization of predator surveillance was found testing both L. migratoria adults and young instars; locusts used the right compound eye to oversee the robot-predator. Right-biased individuals were more stationary over left-biased ones during surveillance of the robot-predator. Individual-level lateralization could avoid predictability during the jumping escape. Population-level lateralization may improve coordination in the swarm during specific group tasks such as predator surveillance. To the best of our knowledge, this is the first report of lateralized predator-prey interactions in insects. Our findings outline the possibility of using biomimetic robots to study predator-prey interaction, avoiding the use of real predators, thus achieving standardized experimental conditions to investigate complex and flexible behaviours. PMID- 28993652 TI - Oxygen vacancy clusters essential for the catalytic activity of CeO2 nanocubes for o-xylene oxidation. AB - Catalytic oxidation of o-xylene was investigated on CeO2 nanocubes calcined at 350, 450, 550, and 650 degrees C, among which the samples calcined at 550 degrees C exhibited the highest activity and long durability. Positron annihilation spectroscopy measurements revealed that the size and distribution of oxygen vacancies for CeO2 nanocubes could be tuned by carefully controlling the calcination temperature. An excellent linear correlation between a factor related to size and density of oxygen vacancy clusters and reaction rate of o-xylene oxidation was revealed on ceria nanocubes. This means that oxygen vacancy clusters with suitable size and distribution are responsible for catalytic reaction via simultaneous adsorption and activation of oxygen and o-xylene. Electron spin resonance spectra revealed that over the CeO2 cubes, water vapor significantly promoted the formation of ?OH radicals with a sharp decrease in the signals relating to oxygen vacancies, accelerating the transformation of o-xylene to the intermediate benzoate species, resulting in an enhancement of catalytic activity. Water thus serves as a "smart" molecule; its introduction into the feed mixture further confirmed the key role of oxygen vacancies in the catalytic performance of CeO2 nanocubes. A possible mechanism of oxygen vacancy formation during the calcination process was also proposed. PMID- 28993653 TI - Ctenophore trees. PMID- 28993654 TI - Ctenophore relationships and their placement as the sister group to all other animals. AB - Ctenophora, comprising approximately 200 described species, is an important lineage for understanding metazoan evolution and is of great ecological and economic importance. Ctenophore diversity includes species with unique colloblasts used for prey capture, smooth and striated muscles, benthic and pelagic lifestyles, and locomotion with ciliated paddles or muscular propulsion. However, the ancestral states of traits are debated and relationships among many lineages are unresolved. Here, using 27 newly sequenced ctenophore transcriptomes, publicly available data and methods to control systematic error, we establish the placement of Ctenophora as the sister group to all other animals and refine the phylogenetic relationships within ctenophores. Molecular clock analyses suggest modern ctenophore diversity originated approximately 350 million years ago +/- 88 million years, conflicting with previous hypotheses, which suggest it originated approximately 65 million years ago. We recover Euplokamis dunlapae-a species with striated muscles-as the sister lineage to other sampled ctenophores. Ancestral state reconstruction shows that the most recent common ancestor of extant ctenophores was pelagic, possessed tentacles, was bioluminescent and did not have separate sexes. Our results imply at least two transitions from a pelagic to benthic lifestyle within Ctenophora, suggesting that such transitions were more common in animal diversification than previously thought. PMID- 28993656 TI - Multiple similarly effective solutions exist for biomedical feature selection and classification problems. AB - Binary classification is a widely employed problem to facilitate the decisions on various biomedical big data questions, such as clinical drug trials between treated participants and controls, and genome-wide association studies (GWASs) between participants with or without a phenotype. A machine learning model is trained for this purpose by optimizing the power of discriminating samples from two groups. However, most of the classification algorithms tend to generate one locally optimal solution according to the input dataset and the mathematical presumptions of the dataset. Here we demonstrated from the aspects of both disease classification and feature selection that multiple different solutions may have similar classification performances. So the existing machine learning algorithms may have ignored a horde of fishes by catching only a good one. Since most of the existing machine learning algorithms generate a solution by optimizing a mathematical goal, it may be essential for understanding the biological mechanisms for the investigated classification question, by considering both the generated solution and the ignored ones. PMID- 28993657 TI - Measuring selection for genes that promote long life in a historical human population. AB - The unusually long lifespans of humans and the persistence of post-reproductive lifespans in women represent evolutionary puzzles because natural selection cannot directly favour continued living in post-menopausal women or elderly men. Suggested sources of indirect selection require genetic correlations between fitness and survival or reproduction at younger ages, reproduction in the opposite sex, or late-life contributions to offspring or grandoffspring fitness. Here we apply quantitative genetic analyses to data from a historical human population to explicitly test these evolutionary genetic hypotheses. Total genetic selection increased the male post-50 lifespans by 0.138 years per generation; 94% of this arose from indirect selection acting to favour early-life fitness in both sexes. These results argue strongly against life-history models of ageing that depend on trade-offs between reproduction and late-life survival. No source of indirect selection for female post-50 lifespan was detected, deepening the mystery of why female post-reproductive survival persists. This result is probably due to recent changes in the genetic architecture of female lifespan, and it highlights the need for similar quantitative genetic analyses of human populations at other points along demographic transitions. PMID- 28993655 TI - Climates on incidence of childhood type 1 diabetes mellitus in 72 countries. AB - We are aimed to systematically assess the worldwide trend in incidence of childhood type 1 diabetes mellitus (CT1DM) from 1965 to 2012 and to discuss whether climate affect incidence of CT1DM. We searched the relevant literatures in detail to judge the effect of different climates on incidence of CT1DM. The climates included Mediterranean, monsoon, oceanic, continental, savanna, and rainforest. According to different climates, we further researched relevant factor such as sunshine durations and latitudes. The overall incidence of CT1DM in 72 countries was 11.43 (95% CI 10.31-12.55) per 100,000 children/yr. The incidence of CT1DM in Oceanic climate [10.56 (8.69-12.42)] is highest compared with other climates; the incidence in 40 degrees -66 degrees 34'N/S [14.71 (12.30 17.29)] is higher than other latitude groups; the incidence in sunshine durations with 3-4 hours per day [15.17 (11.14-19.20)] is highest compared with other two groups; the incidence of CT1DM from 2000 to 2012 [19.58 (14.55-24.60)] is higher than other periods; all p < 0.01. Incidence of CT1DM was increasing from 1965 to 2012, but incidence in Oceanic climate is higher than other climates. Furthermore, it is higher in centers with higher latitude and lower sunshine durations. The climates might play a key role in inducing CT1DM. PMID- 28993658 TI - Fast-charging high-energy lithium-ion batteries via implantation of amorphous silicon nanolayer in edge-plane activated graphite anodes. AB - As fast-charging lithium-ion batteries turn into increasingly important components in forthcoming applications, various strategies have been devoted to the development of high-rate anodes. However, despite vigorous efforts, the low initial Coulombic efficiency and poor volumetric energy density with insufficient electrode conditions remain critical challenges that have to be addressed. Herein, we demonstrate a hybrid anode via incorporation of a uniformly implanted amorphous silicon nanolayer and edge-site-activated graphite. This architecture succeeds in improving lithium ion transport and minimizing initial capacity losses even with increase in energy density. As a result, the hybrid anode exhibits an exceptional initial Coulombic efficiency (93.8%) and predominant fast charging behavior with industrial electrode conditions. As a result, a full-cell demonstrates a higher energy density (>=1060 Wh l-1) without any trace of lithium plating at a harsh charging current density (10.2 mA cm-2) and 1.5 times faster charging than that of conventional graphite.It is desirable to develop fast charging batteries retaining high energy density. Here, the authors report a hybrid anode via incorporation of an implanted amorphous silicon nanolayer and edge-plane-activated graphite, which meets both criteria. PMID- 28993659 TI - Comparative genomics of Lactobacillus kefiranofaciens ZW3 and related members of Lactobacillus. spp reveal adaptations to dairy and gut environments. AB - It is important for probiotics that are currently utilized in the dairy industry to have clear genetic backgrounds. In this study, the genetic characteristics of Lactobacillus kefiranofaciens ZW3 were studied by undertaking a comparative genomics study, and key genes for adaptation to different environments were investigated and validated in vitro. Evidence for horizontal gene transfer resulting in strong self-defense mechanisms was detected in the ZW3 genome. We identified a series of genes relevant for dairy environments and the intestinal tract, particularly for extracellular polysaccharide (EPS) production. Reverse transcription-qPCR (RT-qPCR) revealed significant increases in the relative expression of pgm, ugp, and uge during the mid-logarithmic phase, whereas the expression of pgi was higher at the beginning of the stationary phase. The enzymes encoded by these four genes concertedly regulated carbon flux, which in turn modulated the production of EPS precursors. Moreover, ZW3 tolerated pH 3.5 and 3% bile salt and retained cell surface hydrophobicity and auto-aggregation. In conclusion, we explored the potential of ZW3 for utilization in both the dairy industry and in probiotic applications. Additionally, we elucidated the regulation of the relevant genes involved in EPS production. PMID- 28993660 TI - Molecular evidence of Chlamydia pecorum and arthropod-associated Chlamydiae in an expanded range of marsupials. AB - The order Chlamydiales are biphasic intracellular bacterial pathogens infecting humans and domesticated animals. Wildlife infections have also been reported, with the most studied example being Chlamydia pecorum infections in the koala, an iconic Australian marsupial. In koalas, molecular evidence suggests that spill over from C. pecorum infected livestock imported into Australia may have had a historical or contemporary role. Despite preliminary evidence that other native Australian marsupials also carry C. pecorum, their potential as reservoirs of this pathogen and other Chlamydia-related bacteria (CRBs) has been understudied. Mucosal epithelial samples collected from over 200 native Australian marsupials of different species and geographic regions across Australia were PCR screened for Chlamydiales. Previously described and genetically distinct C. pecorum genotypes and a range of 16S rRNA genotypes sharing similarity to different CRBs in the broader Chlamydiales order were present. One 16S rRNA Chlamydiales genotype recently described in Australian ticks that parasitise native Australian marsupials was also identified. This study provides further evidence that chlamydial infections are widespread in native fauna and that detailed investigations are required to understand the influence these infections have on host species conservation, but also whether infection spill-over plays a role in their epidemiology. PMID- 28993661 TI - Metabolic Signatures in Response to Abscisic Acid (ABA) Treatment in Brassica napus Guard Cells Revealed by Metabolomics. AB - Drought can severely damage crops, resulting in major yield losses. During drought, vascular land plants conserve water via stomatal closure. Each stomate is bordered by a pair of guard cells that shrink in response to drought and the associated hormone abscisic acid (ABA). The activation of complex intracellular signaling networks underlies these responses. Therefore, analysis of guard cell metabolites is fundamental for elucidation of guard cell signaling pathways. Brassica napus is an important oilseed crop for human consumption and biodiesel production. Here, non-targeted metabolomics utilizing gas chromatography mass spectrometry (GC-MS/MS) and liquid chromatography mass spectrometry (LC-MS/MS) were employed for the first time to identify metabolic signatures in response to ABA in B. napus guard cell protoplasts. Metabolome profiling identified 390 distinct metabolites in B. napus guard cells, falling into diverse classes. Of these, 77 metabolites, comprising both primary and secondary metabolites were found to be significantly ABA responsive, including carbohydrates, fatty acids, glucosinolates, and flavonoids. Selected secondary metabolites, sinigrin, quercetin, campesterol, and sitosterol, were confirmed to regulate stomatal closure in Arabidopsis thaliana, B. napus or both species. Information derived from metabolite datasets can provide a blueprint for improvement of water use efficiency and drought tolerance in crops. PMID- 28993662 TI - Stochastic resonance improves vision in the severely impaired. AB - We verified whether a stochastic resonance paradigm (SR), with random interference ("noise") added in optimal amounts, improves the detection of sub threshold visual information by subjects with retinal disorder and impaired vision as it does in the normally sighted. Six levels of dynamic, zero-mean Gaussian noise were added to each pixel of images (13 contrast levels) in which alphabet characters were displayed against a uniform gray background. Images were presented with contrast below the subjective threshold to 14 visually impaired subjects (age: 22-53 yrs.). The fraction of recognized letters varied between 0 and 0.3 at baseline and increased in all subjects when noise was added in optimal amounts; peak recognition ranged between 0.2 and 0.8 at noise sigmas between 6 and 30 grey scale values (GSV) and decreased in all subjects at noise levels with sigma above 30 GSV. The results replicate in the visually impaired the facilitation of visual information processing with images presented in SR paradigms that has been documented in sighted subjects. The effect was obtained with low-level image manipulation and application appears readily possible: it would enhance the efficiency of today vision-improving aids and help in the development of the visual prostheses hopefully available in the future. PMID- 28993663 TI - Renal iron accumulation occurs in lupus nephritis and iron chelation delays the onset of albuminuria. AB - Proteins involved in iron homeostasis have been identified as biomarkers for lupus nephritis, a serious complication of systemic lupus erythematosus (SLE). We tested the hypothesis that renal iron accumulation occurs and contributes to renal injury in SLE. Renal non-heme iron levels were increased in the (New Zealand Black x New Zealand White) F1 (NZB/W) mouse model of lupus nephritis compared with healthy New Zealand White (NZW) mice in an age- and strain dependent manner. Biodistribution studies revealed increased transferrin-bound iron accumulation in the kidneys of albuminuric NZB/W mice, but no difference in the accumulation of non-transferrin bound iron or ferritin. Transferrin excretion was significantly increased in albuminuric NZB/W mice, indicating enhanced tubular exposure and potential for enhanced tubular uptake following filtration. Expression of transferrin receptor and 24p3R were reduced in tubules from NZB/W compared to NZW mice, while ferroportin expression was unchanged and ferritin expression increased, consistent with increased iron accumulation and compensatory downregulation of uptake pathways. Treatment of NZB/W mice with the iron chelator deferiprone significantly delayed the onset of albuminuria and reduced blood urea nitrogen concentrations. Together, these findings suggest that pathological changes in renal iron homeostasis occurs in lupus nephritis, contributing to the development of kidney injury. PMID- 28993664 TI - Fragmentation transitions in a coevolving nonlinear voter model. AB - We study a coevolving nonlinear voter model describing the coupled evolution of the states of the nodes and the network topology. Nonlinearity of the interaction is measured by a parameter q. The network topology changes by rewiring links at a rate p. By analytical and numerical analysis we obtain a phase diagram in p,q parameter space with three different phases: Dynamically active coexistence phase in a single component network, absorbing consensus phase in a single component network, and absorbing phase in a fragmented network. For finite systems the active phase has a lifetime that grows exponentially with system size, at variance with the similar phase for the linear voter model that has a lifetime proportional to system size. We find three transition lines that meet at the point of the fragmentation transition of the linear voter model. A first transition line corresponds to a continuous absorbing transition between the active and fragmented phases. The other two transition lines are discontinuous transitions fundamentally different from the transition of the linear voter model. One is a fragmentation transition between the consensus and fragmented phases, and the other is an absorbing transition in a single component network between the active and consensus phases. PMID- 28993665 TI - Variabilities in retinal function and structure in a canine model of cone-rod dystrophy associated with RPGRIP1 support multigenic etiology. AB - Defects in the cilia gene RPGRIP1 cause Leber congenital amaurosis and cone-rod dystrophy in humans. A form of canine cone-rod dystrophy (cord1) was originally associated with a homozygous insertion in RPGRIP1 (RPGRIP1 ins/ins) as the primary disease locus while a homozygous deletion in MAP9 (MAP9 del/del) was later identified as a modifier associated with the early onset form. However, we find further variability in cone electroretinograms (ERGs) ranging from normal to absent in an extended RPGRIP1 ins/ins canine colony, irrespective of the MAP9 genotype. Ophthalmoscopically, cone ERGabsent RPGRIP1 ins/ins eyes show discolouration of the tapetal fundus with varying onset and disease progression, while sd-OCT reveals atrophic changes. Despite marked changes in cone ERG and retinal morphology, photopic vision-guided behaviour is comparable between normal and cone ERGabsent RPGRIP1 ins/ins littermates. Cone morphology of the dogs lacking cone ERG are truncated with shortened outer and inner segments. Immunohistochemically, cone ERGabsent RPGRIP1 ins/ins retinas have extensive L/M opsin mislocalization, lack CNGB3 labelling in the L/M-cones, and lack GC1 in all cones. Our results indicate that cord1 is a multigenic disease in which mutations in neither RPGRIP1 nor MAP9 alone lead to visual deficits, and additional gene(s) contribute to cone-specific functional and morphologic defects. PMID- 28993666 TI - HIV-infected macrophages and microglia that survive acute infection become viral reservoirs by a mechanism involving Bim. AB - While HIV kills most of the cells it infects, a small number of infected cells survive and become latent viral reservoirs, posing a significant barrier to HIV eradication. However, the mechanism by which immune cells resist HIV-induced apoptosis is still incompletely understood. Here, we demonstrate that while acute HIV infection of human microglia/macrophages results in massive apoptosis, a small population of HIV-infected cells survive infection, silence viral replication, and can reactivate viral production upon specific treatments. We also found that HIV fusion inhibitors intended for use as antiretroviral therapies extended the survival of HIV-infected macrophages. Analysis of the pro- and anti-apoptotic pathways indicated no significant changes in Bcl-2, Mcl-1, Bak, Bax or caspase activation, suggesting that HIV blocks a very early step of apoptosis. Interestingly, Bim, a highly pro-apoptotic negative regulator of Bcl 2, was upregulated and recruited into the mitochondria in latently HIV-infected macrophages both in vitro and in vivo. Together, these results demonstrate that macrophages/microglia act as HIV reservoirs and utilize a novel mechanism to prevent HIV-induced apoptosis. Furthermore, they also suggest that Bim recruitment to mitochondria could be used as a biomarker of viral reservoirs in vivo. PMID- 28993668 TI - Non-Mendelian assortment of homologous autosomes of different sizes in males is the ancestral state in the Caenorhabditis lineage. AB - Organismal genome sizes vary by six orders of magnitude and appear positively correlated with organismal size and complexity. Neutral models have been proposed to explain the broad patterns of genome size variation based on organism population sizes. In the Caenorhabditis genus, hermaphrodite genomes are smaller than those of gonochoristic species. One possible driving force for this genome size difference could be non-random chromosome segregation. In Caenorhabditis elegans, chromosome assortment is non-independent and violates Mendel's second law. In males, the shorter homologue of a heterozygous autosome pair preferentially co-segregates with the X chromosome while the longer one preferentially co-segregates with the nullo-X (O) chromosome in a process we call "skew". Since hermaphrodites preferentially receive the shorter chromosomes and can start populations independently, their genome size would be predicted to decrease over evolutionary time. If skew is an important driver for genome size reduction in hermaphroditic Caenorhabditis species, then it should be present in all congeneric species. In this study, we tested this hypothesis and found that skew is present in all eight examined species. Our results suggest that skew is likely the ancestral state in this genus. More speculatively, skew may drive genome size patterns in hermaphroditic species in other nematodes. PMID- 28993669 TI - Cell-cell communication enhances bacterial chemotaxis toward external attractants. AB - Bacteria are able to coordinate their movement, growth and biochemical activities through cell-cell communication. While the biophysical mechanism of bacterial chemotaxis has been well understood in individual cells, the role of communication in the chemotaxis of bacterial populations is not clear. Here we report experimental evidence for cell-cell communication that significantly enhances the chemotactic migration of bacterial populations, a finding that we further substantiate using numerical simulations. Using a microfluidic approach, we find that E. coli cells respond to the gradient of chemoattractant not only by biasing their own random-walk swimming pattern through the well-understood intracellular chemotaxis signaling, but also by actively secreting a chemical signal into the extracellular medium, possibly through a hitherto unknown communication signal transduction pathway. This extracellular signaling molecule is a strong chemoattractant that attracts distant cells to the food source. The observed behavior may represent a common evolved solution to accelerate the function of biochemical networks of interacting cells. PMID- 28993667 TI - The global distribution of tetrapods reveals a need for targeted reptile conservation. AB - The distributions of amphibians, birds and mammals have underpinned global and local conservation priorities, and have been fundamental to our understanding of the determinants of global biodiversity. In contrast, the global distributions of reptiles, representing a third of terrestrial vertebrate diversity, have been unavailable. This prevented the incorporation of reptiles into conservation planning and biased our understanding of the underlying processes governing global vertebrate biodiversity. Here, we present and analyse the global distribution of 10,064 reptile species (99% of extant terrestrial species). We show that richness patterns of the other three tetrapod classes are good spatial surrogates for species richness of all reptiles combined and of snakes, but characterize diversity patterns of lizards and turtles poorly. Hotspots of total and endemic lizard richness overlap very little with those of other taxa. Moreover, existing protected areas, sites of biodiversity significance and global conservation schemes represent birds and mammals better than reptiles. We show that additional conservation actions are needed to effectively protect reptiles, particularly lizards and turtles. Adding reptile knowledge to a global complementarity conservation priority scheme identifies many locations that consequently become important. Notably, investing resources in some of the world's arid, grassland and savannah habitats might be necessary to represent all terrestrial vertebrates efficiently. PMID- 28993670 TI - Contralateral cortico-ponto-cerebellar pathways reconstruction in humans in vivo: implications for reciprocal cerebro-cerebellar structural connectivity in motor and non-motor areas. AB - Cerebellar involvement in cognition, as well as in sensorimotor control, is increasingly recognized and is thought to depend on connections with the cerebral cortex. Anatomical investigations in animals and post-mortem humans have established that cerebro-cerebellar connections are contralateral to each other and include the cerebello-thalamo-cortical (CTC) and cortico-ponto-cerebellar (CPC) pathways. CTC and CPC characterization in humans in vivo is still challenging. Here advanced tractography was combined with quantitative indices to compare CPC to CTC pathways in healthy subjects. Differently to previous studies, our findings reveal that cerebellar cognitive areas are reached by the largest proportion of the reconstructed CPC, supporting the hypothesis that a CTC-CPC loop provides a substrate for cerebro-cerebellar communication during cognitive processing. Amongst the cerebral areas identified using in vivo tractography, in addition to the cerebral motor cortex, major portions of CPC streamlines leave the prefrontal and temporal cortices. These findings are useful since provide MRI based indications of possible subtending connectivity and, if confirmed, they are going to be a milestone for instructing computational models of brain function. These results, together with further multi-modal investigations, are warranted to provide important cues on how the cerebro-cerebellar loops operate and on how pathologies involving cerebro-cerebellar connectivity are generated. PMID- 28993671 TI - MDSCs are induced after experimental blunt chest trauma and subsequently alter antigen-specific T cell responses. AB - Severe blunt chest trauma (TxT) induces a strong inflammatory response with posttraumatic immune suppression pointing to an impaired adaptive immune response. Since CD11b+Gr-1+-expressing myeloid-derived suppressor cells (MDSCs) are induced after inflammation and suppress T cell responses, MDSC induction and their impact on T cell functions was analysed in an experimental TxT model. MDSCs were induced preferentially in the lung until 24 hours after TxT. Although MDSC numbers were only faintly increased in the spleen, splenic MDSCs isolated after TxT strongly inhibited alloantigen-induced T cell proliferation in vitro. Suppressive activity correlated with increased expression of arginase-1 and iNOS. MDSCs also prevented antigen-induced T cell expansion in vivo, since staphylococcus enterotoxin B (SEB)-induced proliferation of vbeta8+ T cells was impaired in TxT mice in the presence of CD11b+Gr-1+ cells. Surprisingly, MDSCs were not involved in shifting T cells into Th2 cells, characterized by the secretion of cytokines impairing cell-mediated immunity and promoting immunosuppression. Instead, the presence of CD11b+Gr-1+ cells was required for efficient IL-2, IFN-gamma and TNFalpha production after antigenic stimulation, indicating, that elevation of MDSCs early after traumatic injuries might contribute to restrict the initial inflammatory response by alleviating T cell expansion, however, without impeding Th1 functions. PMID- 28993673 TI - Deep-level defects in n-type GaAsBi alloys grown by molecular beam epitaxy at low temperature and their influence on optical properties. AB - Deep-level defects in n-type GaAs1-x Bi x having 0 <= x <= 0.023 grown on GaAs by molecular beam epitaxy at substrate temperature of 378 degrees C have been injvestigated by deep level transient spectroscopy. The optical properties of the layers have been studied by contactless electroreflectance and photoluminescence. We find that incorporating Bi suppresses the formation of GaAs-like electron traps, thus reducing the total trap concentration in dilute GaAsBi layers by over two orders of magnitude compared to GaAs grown under the same conditions. In order to distinguish between Bi- and host-related traps and to identify their possible origin, we used the GaAsBi band gap diagram to correlate their activation energies in samples with different Bi contents. This approach was recently successfully applied for the identification of electron traps in n-type GaAs1-x N x and assumes that the activation energy of electron traps decreases with the Bi (or N)-related downward shift of the conduction band. On the basis of this diagram and under the support of recent theoretical calculations, at least two Bi-related traps were revealed and associated with Bi pair defects, i.e. (VGa+BiGa)-/2- and (AsGa+BiGa)0/1-. In the present work it is shown that these defects also influence the photoluminescence properties of GaAsBi alloys. PMID- 28993672 TI - Oligomerization-primed coiled-coil domain interaction with Ubc13 confers processivity to TRAF6 ubiquitin ligase activity. AB - Ubiquitin ligase TRAF6, together with ubiquitin-conjugating enzyme Ubc13/Uev1, catalyzes processive assembly of unanchored K63-linked polyubiquitin chains for TAK1 activation in the IL-1R/TLR pathways. However, what domain and how it functions to enable TRAF6's processivity are largely uncharacterized. Here, we find TRAF6 coiled-coil (CC) domain is crucial to enable its processivity. The CC domain mediates TRAF6 oligomerization to ensure efficient long polyubiquitin chain assembly. Mutating or deleting the CC domain impairs TRAF6 oligomerization and processive polyubiquitin chain assembly. Fusion of the CC domain to the E3 ubiquitin ligase CHIP/STUB1 renders the latter capable of NF-kappaB activation. Moreover, the CC domain, after oligomerization, interacts with Ubc13/Ub~Ubc13, which further contributes to TRAF6 processivity. Point mutations within the CC domain that weaken TRAF6 interaction with Ubc13/Ub~Ubc13 diminish TRAF6 processivity. Our results reveal that the CC oligomerization primes its interaction with Ubc13/Ub~Ubc13 to confer processivity to TRAF6 ubiquitin ligase activity.Ubiquitin ligase TRAF6 catalyzes assembly of free polyubiquitin chains for TAK1 activation in the IL-1R/TLR pathways, but the mechanism underlying its processivity is unclear. Here, the authors show that TRAF6 coiled-coil oligomerization domain primes its interaction with Ubc13/Ub~Ubc13 to confer processivity. PMID- 28993674 TI - Geometry Optimization with Machine Trained Topological Atoms. AB - The geometry optimization of a water molecule with a novel type of energy function called FFLUX is presented, which bypasses the traditional bonded potentials. Instead, topologically-partitioned atomic energies are trained by the machine learning method kriging to predict their IQA atomic energies for a previously unseen molecular geometry. Proof-of-concept that FFLUX's architecture is suitable for geometry optimization is rigorously demonstrated. It is found that accurate kriging models can optimize 2000 distorted geometries to within 0.28 kJ mol-1 of the corresponding ab initio energy, and 50% of those to within 0.05 kJ mol-1. Kriging models are robust enough to optimize the molecular geometry to sub-noise accuracy, when two thirds of the geometric inputs are outside the training range of that model. Finally, the individual components of the potential energy are analyzed, and chemical intuition is reflected in the independent behavior of the three energy terms [Formula: see text](intra-atomic), [Formula: see text] (electrostatic) and [Formula: see text] (exchange), in contrast to standard force fields. PMID- 28993675 TI - Optical Manipulation of nanoparticles by simultaneous electric and magnetic field enhancement within diabolo nanoantenna. AB - In this paper, we propose and numerically simulate a novel optical trapping process based on the enhancement and the confinement of both magnetic and electric near-fields by using gold Diabolo Antenna (DA). The later was recently proposed to generate huge magnetic near-field when illuminated by linearly polarized wave along its axis. Numerical 3D - FDTD simulation results demonstrate the high confinement of the electromagnetic field in the vicinity of the DA. This enhancement is then exploited for the trapping of nano-particles (NP) as small as 30 nm radius. Results show that the trapping process greatly depends on the particle dimensions and that three different regimes of, trapping at contact, trapping without contact, or pushing can be achieved within the same DA. This doubly resonant structure opens the way to the design of a novel generation of efficient optical nano-tweezers that allow manipulation of nano-particles by simply changing the operation wavelength. PMID- 28993676 TI - Properties analysis of transcription factor gene TasMYB36 from Trichoderma asperellum CBS433.97 and its heterogeneous transfomation to improve antifungal ability of Populus. AB - The transcription of TasMYB36 in the biocontrol species T. asperellum was upregulated in four different pathogenic fermentation broths, suggesting that TasMYB36 plays an important role in the response to biotic stresses. Seventy-nine MYB transcription factors that were homologous to TasMYB36 from six sequenced Trichoderma genomes were analyzed. They were distributed in fourteen clades in the phylogenetic tree. The 79 MYBs contained 113 DNA binding domains, and their amino acid sequences were conserved and were different to those in plants. The promoters of 79 MYBs contained 1374 cis-regulators related to the stress response, such as GCR1 (17.5%) and GCN4 (15.5%). Subsequently, TasMYB36 was integrated into the genome of Populus davidiana * P. alba var. pyramidalis (PdPap poplar), and after co-culture of the transformants (PdPap-TasMYB36s) with Alternaria alternate, the transcription of genes in the jasmonic acid (JA) and salicylic acid (SA) hormone signaling pathways were upregulated; the POD, SOD and CAT activities were enhanced; and the reactive oxygen content was reduced in PdPap-TasMYB36s. The disease spots area on PdPap-TasMYB36s leaves infected by A. alternate were average 0.63% (PdPap-Con: 24.7%). In summary, TasMYB36 of T. asperellum CBS433.97 is an important defense response gene that upregulates other stress response genes and could improve resistance to biotic stresses. PMID- 28993677 TI - Squeezing giant spin states via geometric phase control in cavity-assisted Raman transitions. AB - Squeezing ensemble of spins provides a way to surpass the standard quantum limit in quantum metrology and test the fundamental physics as well, and therefore attracts broad interest. Here we propose an experimentally accessible protocol to squeeze a giant ensemble of spins via the geometric phase control (GPC). Using the cavity-assisted Raman transition (CART) in a double Lambda-type system, we realize an effective Dicke model. Under the condition of vanishing effective spin transition frequency, we find a particular evolution time where the cavity decouples from the spins and the spin ensemble is squeezed considerably. Our scheme combines the CART and the GPC, and has the potential to improve the sensitivity in quantum metrology with spins by about two orders. PMID- 28993678 TI - Erratum: Characterization of Mechanically Matched Hydrogel Coatings to Improve the Biocompatibility of Neural Implants. AB - A correction to this article has been published and is linked from the HTML version of this paper. The error has not been fixed in the paper. PMID- 28993679 TI - Erratum: Sample-based approach can outperform the classical dynamical analysis - experimental confirmation of the basin stability method. AB - A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper. PMID- 28993680 TI - Rheumatoid arthritis and risk for Alzheimer's disease: a systematic review and meta-analysis and a Mendelian Randomization study. AB - Rheumatoid arthritis (RA) patients have been observed to be at a lower risk of developing Alzheimer's Disease (AD). Clinical trials have showed no relationship between nonsteroidal anti-inflammatory drug (NSAID) use and AD. The aim of this study was to establish if there is a causal link between RA and AD. A systematic literature review on RA incidence and its link to AD was carried out according to the PRISMA guidelines. Eight case-control and two population-based studies were included in a random effects meta-analysis. The causal relationship between RA and AD was assessed using Mendelian Randomization (MR), using summary data from the largest RA and AD Genome Wide Association (GWA) and meta-analysis studies to date using a score of 62 RA risk SNPs (p < 5 * 10-8) as instrumental variable (IV). Meta-analysis of the literature showed that RA was associated with lower AD incidence (OR = 0.600, 95% CI 0.46-0.77, p = 1.03 * 10-4). On the contrary, MR analysis did not show any evidence of a causal association between RA and AD (OR = 1.012, 95% CI 0.98-1.04). Although there is epidemiological evidence for an association of RA with lower AD incidence, this association does not appear to be causal. Possible explanations for this discrepancy could include influence from confounding factors such as use of RA medication, selection bias and differential RA diagnosis. PMID- 28993681 TI - Equiaxial Strain Modulates Adipose-derived Stem Cell Differentiation within 3D Biphasic Scaffolds towards Annulus Fibrosus. AB - Recurrence of intervertebral disc (IVD) herniation is the most important factor leading to chronic low back pain and subsequent disability after discectomy. Efficacious annulus fibrosus (AF) repair strategy that delivers cells and biologics to IVD injury site is needed to limit the progression of disc degeneration and promote disc self-regeneration capacities after discectomy procedures. In this study, a biphasic mechanically-conditioned scaffold encapsulated with human adipose-derived stem cells (ASCs) is studied as a potential treatment strategy for AF defects. Equiaxial strains and frequencies were applied to ASCs-encapsulated scaffolds to identify the optimal loading modality to induce AF differentiation. Equiaxial loading resulted in 2-4 folds increase in secretion of extracellular matrix proteins and the reorganization of the matrix fibers and elongations of the cells along the load direction. Further, the equiaxial load induced region-specific differentiation of ASCs within the inner and outer regions of the biphasic scaffolds. Gene expression of AF markers was upregulated with 5-30 folds within the equiaxially loaded biphasic scaffolds compared to unstrained samples. The results suggest that there is a specific value of equiaxial strain favorable to differentiate ASCs towards AF lineage and that ASCs-embedded biphasic scaffold can potentially be utilized to repair the AF defects. PMID- 28993682 TI - Olaparib modulates DNA repair efficiency, sensitizes cervical cancer cells to cisplatin and exhibits anti-metastatic property. AB - PARP1 trapping at DNA lesion by pharmacological inhibitors has been exploited in several cancers exhibiting defects in DNA repair mechanisms. PARP1 hyperactivation is involved in therapeutic resistance in multiple cancers. The role of PARP1 in cervical cancer (CC) resistance and implication of PARP inhibitor is yet to be elucidated. Our data demonstrates significantly higher expression of PARP1 in primary cervical tumors and CC cell lines SiHa and ME180. Upon cisplatin treatment CC cells display significant overexpression of PARP1 and its hyperactivation. PARP inhibitor olaparib shows significant anti-proliferative effect on CC cells and drive loss of clonogenic survival and enhanced cell death in combination with cisplatin. PARP inhibited cells show delay in resolution of gammaH2A.X foci and prolonged late S and G2-M phase arrest resulting in apoptosis. Further, PARP inhibition disrupts the localization of base excision repair (BER) effector XRCC1 and non-homologous end joining (NHEJ) proteins Ku80 and XRCC4. Due to disrupted relocation of repair factors, cisplatin induced stalled replication forks collapse and convert into double strand breaks (DSBs). Interestingly, PARP inhibition also shows anti-migratory and anti-invasive properties in CC cells, increases anchorage independent cell death and induces anoikis. Collectively, our data demonstrates therapeutic potential of PARP inhibitor in cervical cancer. PMID- 28993684 TI - The prognostic correlation of AFP level at diagnosis with pathological grade, progression, and survival of patients with hepatocellular carcinoma. AB - The purpose of this study was to conduct a comprehensive study of the clinical correlation between the alpha-fetoprotein (AFP) level at diagnosis and pathological grades, progression, and survival of patients with hepatocellular carcinoma (HCC). A total of 78,743 patients in Surveillance, Epidemiology, and End Results Program (SEER)-registered HCC was analyzed. The AFP test results for patients with HCC were mainly recorded as AFP-negative and AFP-positive. Logistic regression analysis revealed that the AFP level at diagnosis was an independent risk factor of pathological grade (odds ratio [OR], 2.559; 95% confidence interval [CI], 2.075-3.157; P < 0.001), TNM-7 stage (OR, 2.794; CI, 2.407-3.242; P < 0.001), and tumor size (OR, 1.748; 95% CI, 1.574-1.941; P < 0.001). Multivariable Cox regression analyses identified AFP level as an independent predictor of survival risk of patients with HCC who did not undergo surgery (hazard ratio [HR], 1.660; 95% CI, 1.534-1.797; P < 0.001), and those who underwent surgery (HR, 1.534; 95% CI, 1.348-1.745; P < 0.001). The AFP level at diagnosis was an independent risk predictor associated with pathological grade, progression, and survival. Further, surgery may not significantly reverse the adverse effects of AFP-positive compared with AFP-negative. PMID- 28993683 TI - Short term changes in the proteome of human cerebral organoids induced by 5-MeO DMT. AB - Dimethyltryptamines are entheogenic serotonin-like molecules present in traditional Amerindian medicine recently associated with cognitive gains, antidepressant effects, and changes in brain areas related to attention. Legal restrictions and the lack of adequate experimental models have limited the understanding of how such substances impact human brain metabolism. Here we used shotgun mass spectrometry to explore proteomic differences induced by 5-methoxy N,N-dimethyltryptamine (5-MeO-DMT) on human cerebral organoids. Out of the 6,728 identified proteins, 934 were found differentially expressed in 5-MeO-DMT-treated cerebral organoids. In silico analysis reinforced previously reported anti inflammatory actions of 5-MeO-DMT and revealed modulatory effects on proteins associated with long-term potentiation, the formation of dendritic spines, including those involved in cellular protrusion formation, microtubule dynamics, and cytoskeletal reorganization. Our data offer the first insight about molecular alterations caused by 5-MeO-DMT in human cerebral organoids. PMID- 28993685 TI - microRNA profiling in lung tissue and bronchoalveolar lavage of cigarette smoke exposed mice and in COPD patients: a translational approach. AB - Chronic obstructive pulmonary disease (COPD) is characterized by a progressive airflow limitation and is associated with a chronic inflammatory response in both airways and lungs. microRNAs (miRNAs) are often highly conserved between species and have an intricate role within homeostatic conditions and immune responses. Also, miRNAs are dysregulated in smoking-associated diseases. We investigated the miRNA profile of 523 miRNAs by stem-loop RT-qPCR in lung tissue and cell-free bronchoalveolar lavage (BAL) supernatant of mice exposed to air or cigarette smoke (CS) for 4 or 24 weeks. After 24 weeks of CS exposure, 31 miRNAs were differentially expressed in lung tissue and 78 in BAL supernatant. Next, we correlated the miRNA profiling data to inflammation in BAL and lung, obtained by flow cytometry or ELISA. In addition, we surveyed for overlap with newly assessed miRNA profiles in bronchial biopsies and with previously assessed miRNA profiles in lung tissue and induced sputum supernatant of smokers with COPD. Several miRNAs showed concordant differential expression between both species including miR-31*, miR-155, miR-218 and let-7c. Thus, investigating miRNA profiling data in different compartments and both species provided accumulating insights in miRNAs that may be relevant in CS-induced inflammation and the pathogenesis of COPD. PMID- 28993686 TI - Multiobjective differential evolution-based multifactor dimensionality reduction for detecting gene-gene interactions. AB - Epistasis within disease-related genes (gene-gene interactions) was determined through contingency table measures based on multifactor dimensionality reduction (MDR) using single-nucleotide polymorphisms (SNPs). Most MDR-based methods use the single contingency table measure to detect gene-gene interactions; however, some gene-gene interactions may require identification through multiple contingency table measures. In this study, a multiobjective differential evolution method (called MODEMDR) was proposed to merge the various contingency table measures based on MDR to detect significant gene-gene interactions. Two contingency table measures, namely the correct classification rate and normalized mutual information, were selected to design the fitness functions in MODEMDR. The characteristics of multiobjective optimization enable MODEMDR to use multiple measures to efficiently and synchronously detect significant gene-gene interactions within a reasonable time frame. Epistatic models with and without marginal effects under various parameter settings (heritability and minor allele frequencies) were used to assess existing methods by comparing the detection success rates of gene-gene interactions. The results of the simulation datasets show that MODEMDR is superior to existing methods. Moreover, a large dataset obtained from the Wellcome Trust Case Control Consortium was used to assess MODEMDR. MODEMDR exhibited efficiency in identifying significant gene-gene interactions in genome-wide association studies. PMID- 28993688 TI - Modulation of electronic transport properties in armchair phosphorene nanoribbons by doping and edge passivation. AB - The electronic structures and transport properties of group IV atoms (C, Si, Ge) doped armchair phosphorene nanoribbons (APNRs) are investigated using first principles calculations, considering different edge passivation. The results show that the C, Si, Ge dopants can induce the transition occur from semiconductor to metal in the APNRs. The negative differential resistance (NDR) behavior in the doped APNR system is robust with respect to the doping concentration and edge passivation type. However, their current peak positions and peak-to-valley ratio (PVR) values are correlated with doping concentration and edge passivation type. In particular, for the C, Si-doped APNRs, the low bias NDR behavior with the PVR (105-108) can be observed when doping concentration is low in the APNRs with the F and H edge passivation. These results may play an important role for the fabrication of future low power consumption nano-electronic devices. PMID- 28993687 TI - Dynamic mRNA and miRNA expression analysis in response to hypoxia and reoxygenation in the blunt snout bream (Megalobrama amblycephala). AB - Adaptation to hypoxia is a complex process involving various pathways and regulation mechanisms. A better understanding of the genetic influence on these mechanisms could permit selection for hypoxia-sensitive fish. To aid this understanding, an integrated analysis of miRNA and mRNA expression was performed in Megalobrama amblycephala under four acute hypoxia and reoxygenation stages. A number of significantly differentially-expressed miRNAs and genes associated with oxidative stress were identified, and their functional characteristics were revealed by GO function and KEGG pathway analysis. They were found to be involved in HIF-1 pathways known to affect energy metabolism and apoptosis. MiRNA-mRNA interaction pairs were detected from comparison of expression between the four different stages. The function annotation results also showed that many miRNA mRNA interaction pairs were likely to be involved in regulating hypoxia stress. As a unique resource for gene expression and regulation during hypoxia and reoxygenation, this study could provide a starting point for further studies to better understand the genetic background of hypoxia stress. PMID- 28993689 TI - Orbital Angular Momentum (OAM) Antennas via Mode Combining and Canceling in Near field. AB - Orbital angular momentum (OAM) mode combining and canceling in the near-field was investigated using a Cassegrain dual-reflectarray antenna composed of multiple microstrip patches on the main and sub-reflectarrays. Microstrip patches on dielectric substrates were designed to radiate the particular OAM modes for arithmetic mode combining, where two OAM wave-generating reflectarrays are very closely placed in the near-field. We conducted near-field antenna measurements at 18 [GHz] by manually replacing the sub-reflectarray substrates with different OAM mode numbers of 0, +/-1, when the OAM mode number of the main reflectarray was fixed to +1. We subsequently checked the azimuthal phase distributions of the reflected total electromagnetic waves in the near-field, and verified that the OAM waves mutually reflected from the main and sub-reflectarrays are added or subtracted to each other according to their OAM mode numbers. Based on our proposal, an OAM mode-canceling reflectarray antenna was designed, and the following measurements indicate that the antenna has a better reflection bandwidth and antenna gain than a conventional reflectarray antenna. The concept of OAM mode canceling in the near-field can contribute widely to a new type of low-profile, broad-reflection bandwidth, and high-gain antenna. PMID- 28993690 TI - Spred2-deficiecy Protects Mice from Polymicrobial Septic Peritonitis by Enhancing Inflammation and Bacterial Clearance. AB - Sepsis is an infection-induced systemic inflammatory syndrome and a major cause of death for critically ill patients. Here, we examined whether the absence of Sprouty-related EVH1-domain-containing protein 2 (Spred2), a negative regulator of the Ras/Raf/ERK/MAPK pathway, influences host defense against polymicrobial sepsis (PMS) induced by cecal ligation and puncture (CLP). Compared to wild-type mice, Spred2-/- mice exhibited higher survival rates with increased level of leukocyte infiltration and local chemokine production and reduced plasma and peritoneal bacterial loads after CLP. The MEK inhibitor U0126 significantly reduced LPS-induced chemokine production by Spred2-/- resident macrophages in vitro, and decreased CLP-induced leukocyte infiltration in vivo. Spred2-/- resident macrophages, but not neutrophils or elicited macrophages, exhibited increased phagocytic activity. Interestingly, surface expression of complement receptor 1/2 (CR1/2) was increased in Spred2-/- resident macrophages in response to lipopolysaccharide in a manner dependent on the ERK/MAPK pathway, and blocking CR1/2 in vivo resulted in reduced leukocyte infiltration and increased bacterial loads after CLP. Taken together, our results indicate that Spred2-deficiency protects mice from PMS via increased activation of the ERK/MAPK pathway and subsequent increase in innate immune responses. Thus, inhibiting Spred2 may present a novel means to prevent the development of PMS. PMID- 28993691 TI - Fermi surface topology and magnetotransport in semimetallic LuSb. AB - Several rare-earth monopnictides were shown to exhibit extreme magnetoresistance and field-induced low-temperature plateau of electrical resistivity. These features are also hallmarks of topological semimetals, thus the family is intensively explored with respect to magneto-transport properties and possible hosting Dirac fermion states. We report a comprehensive investigation of Fermi surface and electrical transport properties of LuSb, another representative of this family. At low temperatures, the magnetoresistance of LuSb was found to exceed 3000% without saturation in fields up to 9 T. Analysis of the Hall effect and the Shubnikov-de Haas oscillations revealed that the Fermi surface of this compound consists of several pockets originating from fairly compensated multi band electronic structure, in full accordance with our first-principles calculations. Observed magnetotransport properties of LuSb can be attributed to the topology of three-dimensional Fermi surface and a compensation of electron and hole contributions. PMID- 28993692 TI - Dissecting the mycobacterial cell envelope and defining the composition of the native mycomembrane. AB - The mycobacterial envelope is unique, containing the so-called mycomembrane (MM) composed of very-long chain fatty acids, mycolic acids (MA). Presently, the molecular composition of the MM remains unproven, due to the diversity of methods used for determining its composition. The plasma membranes (PM) and the native MM containing cell walls (MMCW) of two rapid-growing mycobacterial species, Mycobacterium aurum and M. smegmatis, were isolated from their cell lysates by differential ultracentrifugation. Transmission electron microscopy and biochemical analyses demonstrated that the two membranes were virtually pure. Bottom-up quantitative proteomics study indicated a different distribution of more than 2,100 proteins between the PM and MMCW. Among these, the mannosyltransferase PimB, galactofuranosyltransferase GlfT2, Cytochrome p450 and ABC transporter YjfF, were most abundant in the PM, which also contain lipoglycans, phospholipids, including phosphatidylinositol mannosides, and only a tiny amount of other glycolipids. Antigen85 complex proteins, porins and the putative transporters MCE protein family were mostly found in MMCW fraction that contains MA esterifying arabinogalactan, constituting the inner leaflet of MM. Glycolipids, phospholipids and lipoglycans, together with proteins, presumably composed the outer leaflet of the MM, a lipid composition that differs from that deduced from the widely used extraction method of mycobacterial cells with dioctylsulfosuccinate sodium. PMID- 28993693 TI - Uroplakin traffic through the Golgi apparatus induces its fragmentation: new insights from novel in vitro models. AB - Uroplakins (UPs) play an essential role in maintaining an effective urothelial permeability barrier at the level of superficial urothelial cell (UC) layer. Although the organization of UPs in the apical plasma membrane (PM) of UCs is well known, their transport in UCs is only partially understood. Here, we dissected trafficking of UPs and its differentiation-dependent impact on Golgi apparatus (GA) architecture. We demonstrated that individual subunits UPIb and UPIIIa are capable of trafficking from the endoplasmic reticulum to the GA in UCs. Moreover, UPIb, UPIIIa or UPIb/UPIIIa expressing UCs revealed fragmentation and peripheral redistribution of Golgi-units. Notably, expression of UPIb or UPIb/UPIIIa triggered similar GA fragmentation in MDCK and HeLa cells that do not express UPs endogenously. The colocalization analysis of UPIb/UPIIIa-EGFP and COPI, COPII or clathrin suggested that UPs follow constitutively the post-Golgi route to the apical PM. Depolymerisation of microtubules leads to complete blockade of the UPIb/UPIIIa-EGFP post-Golgi transport, while disassembly of actin filaments shows significantly reduced delivery of UPIb/UPIIIa-EGFP to the PM. Our findings show the significant effect of the UPs expression on the GA fragmentation, which enables secretory Golgi-outpost to be distributed as close as possible to the sites of cargo delivery at the PM. PMID- 28993694 TI - Quantifying the relative immune cell activation from whole tissue/organ-derived differentially expressed gene data. AB - Evaluation of immune responses in individual immune cell types is important for the development of new medicines. Here, we propose a computational method designated ICEPOP (Immune CEll POPulation) to estimate individual immune cell type responses from bulk tissue and organ samples. The relative gene responses are scored for each cell type by using the data from differentially expressed genes derived from control- vs drug-treated sample pairs, and the data from public databases including ImmGen and IRIS, which contain gene expression profiles of a variety of immune cells. By ICEPOP, we analysed cell responses induced by vaccine-adjuvants in the mouse spleen, and extended the analyses to human peripheral blood mononuclear cells and gut biopsy samples focusing on human papilloma virus vaccination and inflammatory bowel disease treatment with Infliximab. In both mouse and human datasets, our method reliably quantified the responding immune cell types and provided insightful information, demonstrating that our method is useful to evaluate immune responses from bulk sample-derived gene expression data. ICEPOP is available as an interactive web site ( https://vdynamics.shinyapps.io/icepop/ ) and Python package ( https://github.com/ewijaya/icepop ). PMID- 28993695 TI - Measurement of linear response functions in Nuclear Magnetic Resonance. AB - We measure multi-time correlation functions of a set of Pauli operators on a two level system, which can be used to retrieve its associated linear response functions. The two-level system is an effective spin constructed from the nuclear spins of 1H atoms in a solution of 13C-labeled chloroform. Response functions characterize the linear response of the system to a family of perturbations, allowing us to compute physical quantities such as the magnetic susceptibility of the effective spin. We use techniques exported from quantum information to measure time correlations on the two-level system. This approach requires the use of an ancillary qubit encoded in the nuclear spins of the 13C atoms and a sequence of controlled operations. Moreover, we demonstrate the ability of such a quantum platform to compute time-correlation functions of arbitrary order, which relate to higher-order corrections of perturbative methods. Particularly, we show three-time correlation functions for arbitrary times, and we also measure time correlation functions at fixed times up to tenth order. PMID- 28993696 TI - An eQTL variant of ZXDC is associated with IFN-gamma production following Mycobacterium tuberculosis antigen-specific stimulation. AB - There is a large inter-individual variability in the response to Mycobacterium tuberculosis infection. In previous linkage analyses, we identified a major locus on chromosome region 8q controlling IFN-gamma production after stimulation with live BCG (Bacillus Calmette-Guerin), and a second locus on chromosome region 3q affecting IFN-gamma production triggered by the 6-kDa early secretory antigen target (ESAT-6), taking into account the IFN-gamma production induced by BCG (IFNgamma-ESAT6BCG). High-density genotyping and imputation identified ~100,000 variants within each linkage region, which we tested for association with the corresponding IFN-gamma phenotype in families from a tuberculosis household contact study in France. Significant associations were replicated in a South African familial sample. The most convincing association observed was that between the IFNgamma-ESAT6BCG phenotype and rs9828868 on chromosome 3q (p = 9.8 * 10-6 in the French sample). This variant made a significant contribution to the linkage signal (p < 0.001), and a trend towards the same association was observed in the South African sample. This variant was reported to be an eQTL of the ZXDC gene, biologically linked to monocyte IL-12 production through CCL2/MCP1. The identification of rs9828868 as a genetic driver of IFNgamma production in response to mycobacterial antigens provides new insights into human anti tuberculosis immunity. PMID- 28993697 TI - N-terminal gelsolin fragment potentiates TRAIL mediated death in resistant hepatoma cells. AB - TNF-alpha related apoptosis-inducing ligand (TRAIL) selectively kills tumor cells, without damaging normal cells. TRAIL receptors facilitate induction of apoptosis for selective elimination of malignant cells. However, some cancer cells have developed resistances to TRAIL which limits anticancer potential. Gelsolin, a multifunctional actin-binding protein, mediates cell death involving the TRAIL receptors in the hepatic stellate cell line, LX2. Here, we have shown that conditioned medium (CM) containing gelsolin fragments or an N-terminal gelsolin fragment (amino acid residues 1-70) in the presence of TRAIL impairs cell viability of TRAIL resistant transformed human hepatocytes (HepG2). Cell growth regulation by CM and TRAIL was associated with the modulation of p53/Mdm2, Erk and Akt phosphorylation status. The use of N-terminal gelsolin peptide1-70 alone or in combination with TRAIL, induced inhibition of Akt phosphorylation and key survival factors, Mdm2 and Survivin. Treatment of cells with an Akt activator SC79 or p53 siRNA reduced the effects of the N-terminal gelsolin fragment and TRAIL. Together, our study suggests that the N-terminal gelsolin fragment enhances TRAIL-induced loss of cell viability by inhibiting phosphorylation of Akt and promoting p53 function, effecting cell survival. PMID- 28993698 TI - Structural decomposition of decadal climate prediction errors: A Bayesian approach. AB - Decadal climate predictions use initialized coupled model simulations that are typically affected by a drift toward a biased climatology determined by systematic model errors. Model drifts thus reflect a fundamental source of uncertainty in decadal climate predictions. However, their analysis has so far relied on ad-hoc assessments of empirical and subjective character. Here, we define the climate model drift as a dynamical process rather than a descriptive diagnostic. A unified statistical Bayesian framework is proposed where a state space model is used to decompose systematic decadal climate prediction errors into an initial drift, seasonally varying climatological biases and additional effects of co-varying climate processes. An application to tropical and south Atlantic sea-surface temperatures illustrates how the method allows to evaluate and elucidate dynamic interdependencies between drift, biases, hindcast residuals and background climate. Our approach thus offers a methodology for objective, quantitative and explanatory error estimation in climate predictions. PMID- 28993699 TI - Effect of a positive Sea Surface Temperature anomaly on a Mediterranean tornadic supercell. AB - Extreme events represent a topic of paramount importance and a challenge for modelling investigations. Due to the need of high-resolution models, the study of severe localized convective phenomena is even more critical, especially in relation to changes in forcing factors, such as sea surface temperatures (SSTs), in future climate scenarios. Here, we analyze the effect of changes in SSTs on the intensity of a tornadic supercell in the Mediterranean through modelling investigations. We show dramatic (nonlinear) changes for updraft helicity and vertical velocity, which measure the intensity of the supercell, even for variations of SST only of + /-1 K. PMID- 28993700 TI - Vegetation morphologic and aerodynamic characteristics reduce aeolian erosion. AB - ABSRACT: Vegetation cover is crucial to controlling aeolian erosion but highly efficient vegetation is critical. How this efficiency is influenced by vegetation response to airflow is not clear. Here we evaluate the responses of Cosmos bipinnatus and Ligustrum lucidum Ait to a range of wind speeds in a wind tunnel. For both species, we calculate shelter effect and sand flux. We show that plant effectiveness in reducing wind speed and sediment transport is linked to their aerodynamic response to airflow which results from their morphology. We demonstrate that in low-density cover the flow-response and resistance of individuals is most critical in the optimal effectiveness of a canopy. Our wind tunnel experiment suggests that vegetation morphology and structure must be priority parameters in facilitating aeolian erosion control. PMID- 28993701 TI - Parkinson's disease-related DJ-1 functions in thiol quality control against aldehyde attack in vitro. AB - DJ-1 (also known as PARK7) has been identified as a causal gene for hereditary recessive Parkinson's disease (PD). Consequently, the full elucidation of DJ-1 function will help decipher the molecular mechanisms underlying PD pathogenesis. However, because various, and sometimes inconsistent, roles for DJ-1 have been reported, the molecular function of DJ-1 remains controversial. Recently, a number of papers have suggested that DJ-1 family proteins are involved in aldehyde detoxification. We found that DJ-1 indeed converts methylglyoxal (pyruvaldehyde)-adducted glutathione (GSH) to intact GSH and lactate. Based on evidence that DJ-1 functions in mitochondrial homeostasis, we focused on the possibility that DJ-1 protects co-enzyme A (CoA) and its precursor in the CoA synthetic pathway from aldehyde attack. Here, we show that intact CoA and beta alanine, an intermediate in CoA synthesis, are recovered from methylglyoxal adducts by recombinant DJ-1 purified from E. coli. In this process, methylglyoxal is converted to L-lactate rather than the D-lactate produced by a conventional glyoxalase. PD-related pathogenic mutations of DJ-1 (L10P, M26I, A104T, D149A, and L166P) impair or abolish detoxification activity, suggesting a pathological significance. We infer that a key to understanding the biological function of DJ 1 resides in its methylglyoxal-adduct hydrolase activity, which protects low molecular thiols, including CoA, from aldehydes. PMID- 28993703 TI - Zebra Finch chicks recognise parental scent, and retain chemosensory knowledge of their genetic mother, even after egg cross-fostering. AB - Mechanisms underlying parent-offspring recognition in birds have fascinated researchers for centuries. Yet, the possibility that chicks recognise parental odour at hatching has been completely overlooked, despite the fact that olfaction is one of the first sensory modalities to develop, and social chemosignals occur in avian taxa. Here we show that Zebra Finch chicks (Taeniopygia guttata) are capable of identifying parental odours at hatching. In our first experiment, chicks begged significantly longer in response to the odour of their genetic mother or father compared to the odour of a non-relative of the same sex and reproductive status. In a second experiment, we cross-fostered eggs and tested the response of hatchlings to the scent of genetic vs. foster parents. Chicks from cross-fostered eggs responded significantly more to the odour of their genetic mother than their foster mother, but exhibited no difference in response to genetic vs. foster fathers. This is the first evidence that embryonic altricial birds are capable of acquiring chemosensory knowledge of their parents during early development, and retain chemical familiarity with their genetic mother despite egg cross-fostering. Furthermore our data reveals that kin recognition in birds can develop without any association with a genetic parent at hatching. PMID- 28993702 TI - ERV1 Overexpression in Myeloid Cells Protects against High Fat Diet Induced Obesity and Glucose Intolerance. AB - Non-resolving inflammation is a central pathologic component of obesity, insulin resistance, type 2 diabetes and associated morbidities. The resultant hyperglycemia is deleterious to the normal function of many organs and its control significantly improves survival and quality of life for patients with diabetes. Macrophages play critical roles in both onset and progression of obesity-associated insulin resistance. Here we show that systemic activation of inflammation resolution prevents from morbid obesity and hyperglycemia under dietary overload conditions. In gain-of-function studies using mice overexpressing the human resolvin E1 receptor (ERV1) in myeloid cells, monocyte phenotypic shifts to increased patrolling-to-inflammatory ratio controlled inflammation, reduced body weight gain and protected from hyperglycemia on high fat diet. Administration of a natural ERV1 agonist, resolvin E1, recapitulated the pro-resolving actions gained by ERV1 overexpression. This protective metabolic impact is in part explained by systemic activation of resolution programs leading to increased synthesis of specialized pro-resolving mediators. PMID- 28993704 TI - Interfacial contact stiffness of fractal rough surfaces. AB - In this work we describe a theoretical model that predicts the interfacial contact stiffness of fractal rough surfaces by considering the effects of elastic and plastic deformations of the fractal asperities. We also develop an original test rig that simulates dovetail joints for turbo machinery blades, which can fine tune the normal contact load existing between the contacting surfaces of the blade root. The interfacial contact stiffness is obtained through an inverse identification method in which finite element simulations are fitted to the experimental results. Excellent agreement is observed between the contact stiffness predicted by the theoretical model and by the analogous experimental results. We demonstrate that the contact stiffness is a power law function of the normal contact load with an exponent alpha within the whole range of fractal dimension D(1 < D < 2). We also show that for 1 < D < 1.5 the Pohrt-Popov behavior (alpha = 1/(3 - D)) is valid, however for 1.5 < D < 2, the exponent alpha is different and equal to 2(D - 1)/D. The diversity between the model developed in the work and the Pohrt-Popov one is explained in detail. PMID- 28993705 TI - A vicious loop of fatty acid-binding protein 4 and DNA methyltransferase 1 promotes acute myeloid leukemia and acts as a therapeutic target. AB - Aberrant DNA methylation mediated by deregulation of DNA methyltransferases (DNMT) is a key hallmark of acute myeloid leukemia (AML), yet efforts to target DNMT deregulation for drug development have lagged. We previously demonstrated that upregulation of fatty acid-binding protein 4 (FABP4) promotes AML aggressiveness through enhanced DNMT1-dependent DNA methylation. Here, we demonstrate that FABP4 upregulation in AML cells occurs through vascular endothelial growth factor (VEGF) signaling, thus elucidating a crucial FABP4 DNMT1 regulatory feedback loop in AML biology. We show that FABP4 dysfunction by its selective inhibitor BMS309403 leads to downregulation of DNMT1, decrease of global DNA methylation and re-expression of p15INK4B tumor suppressor gene by promoter DNA hypomethylation in vitro, ex vivo and in vivo. Functionally, BMS309403 suppresses cell colony formation, induces cell differentiation, and, importantly, impairs leukemic disease progression in mouse models of leukemia. Our findings highlight AML-promoting properties of the FABP4-DNMT1 vicious loop, and identify an attractive class of therapeutic agents with a high potential for clinical use in AML patients. The results will also assist in establishing the FABP4-DNMT1 loop as a target for therapeutic discovery to enhance the index of current epigenetic therapies. PMID- 28993706 TI - Rare-Earth Free Self-Activated Graphene Quantum Dots and Copper-Cysteamine Phosphors for Enhanced White Light-Emitting-Diodes under Single Excitation. AB - Rare-earth (RE) based phosphors are attractive due to their potential applications. However, owing to the resource issue, these kinds of phosphors are expensive and costly. On the contrary, as for phosphor-convert white light emitting-diodes (pc-WLEDs), a solution-processed tunable warm white emission LED composite is fabricated in this study under single excitation, with both RE free phosphors graphene quantum dots (GQDs) and Copper-Cysteamine (Cu-Cy). By using microwave-assisted wet-chemical method and with graphite as raw material, cold white fluorescence of the GQDs is obtained. Cu-Cy which shows intense photoluminescence in the red region has the structure where both the thio and amine groups connected with copper and forming cysteamine. Warm white light is achieved by mixing the two self-activated RE free phosphors at the weight ratio of 1: 1.7 under the excitation at 365 nm. The designed optimal LED device has the properties of CIE (x, y) = (0.341, 0.327), T = 4436 K, R = 87.9 EQE = 0.31%. The experimental results demonstrate that RE free phosphor(s) excited under a single chip can open up a new avenue to develop much lower device for warm WLEDs. PMID- 28993707 TI - Effects of active commuting and leisure-time exercise on fat loss in women and men with overweight and obesity: a randomized controlled trial. AB - BACKGROUND: Aerobic exercise is recommended for weight management but energy balance is often less negative than predicted from exercise energy expenditure (ExEE). OBJECTIVE: To examine effects of active commuting and leisure-time exercise on fat loss in women and men with overweight and obesity. METHODS: We randomized 130 younger, physically inactive women and men with overweight and obesity (body mass index: 25-35 kg m-2) to 6 months of habitual lifestyle (control; CON, n=18), active commuting (BIKE, n=35) or leisure-time exercise of moderate (MOD, 50% VO2peak reserve, n=39) or vigorous intensity (VIG, 70% VO2peak reserve, n=38). The primary outcome was change in fat mass measured by dual energy X-ray absorptiometry, which was analyzed intention-to-treat. Accumulated energy balance was calculated based on changes in body composition, and ExEE was calculated based on heart rate monitoring during exercise. RESULTS: Testing at 3 and 6 months was completed by 95 and 90 participants, respectively. Fat mass was reduced after 3 and 6 months in BIKE (3 months: -3.6 (-5.5; -1.7) kg (mean (95% CI)); 6 months: -4.2 (-6.6; -1.9) kg; both: P<0.001), MOD (3 months: -2.2 (-3.9; 0.4) kg; 6 months: -2.6 (-4.8; -0.5) kg, both: P<0.02) and VIG (3 months: -3.4 ( 5.2; -1.7) kg; 6 months: -4.5 (-6.6; -2.3) kg; both: P<0.001) compared with CON. Furthermore, fat loss was greater in VIG compared with MOD (6 months: -1.8 (-3.6; -0.1) kg, P=0.043). Based on the ExEE and the accumulated energy balance MOD compensated for the ExEE (77 (48; 106) %) but not BIKE (38 (-18; 95) %) and VIG (21 (-14; 55) %). CONCLUSIONS: A meaningful fat loss was obtained by 6 months of active commuting and leisure-time exercise, but fat loss was greater with vigorous compared with moderate intensity exercise. Active commuting is an alternative to leisure-time exercise in the management of overweight and obesity. The trial was registered at clinicaltrials.gov as NCT01962259 (main trial) and NCT01973686 (energy metabolism sub-study). PMID- 28993708 TI - Body mass index is associated with cortical thinning with different patterns in mid- and late-life. AB - OBJECTIVE: High BMI at midlife is associated with increased risk of dementia as well as faster decline in cognitive function. In late-life, however, high BMI has been found to be associated with both increased and decreased dementia risk. The objective of this study was to investigate the neural substrates of this age related change in body mass index (BMI) risk. METHODS: We measured longitudinal cortical thinning over the whole brain, based on magnetic resonance imaging scans for 910 individuals aged 44-66 years at baseline. Subjects were sampled from a large population study (PATH, Personality and Total Health through Life). After attrition and exclusions, the final analysis was based on 792 individuals, including 387 individuals aged 60-66 years and 405 individuals aged 44-49 years. A mixed-effects model was used to test the association between cortical thinning and baseline BMI, as well as percentage change in BMI. RESULTS: Increasing BMI was associated with increased cortical thinning in posterior cingulate at midlife (0.014 mm kg-1 m-2, confidence interval; CI=0.005, 0.023, P<0.05 false discovery rate (FDR) corrected). In late-life, increasing BMI was associated with reduced cortical thickness, most prominently in the right supramarginal cortex (0.010 mm kg-1 m-2, CI=0.005-0.016, P<0.05 FDR corrected), as well as frontal regions. In late-life, decreasing BMI was also associated with increased cortical thinning, including right caudal middle frontal cortex (0.014 mm kg-1 m-2 (CI=0.006-0.023, P<0.05 FDR corrected). CONCLUSIONS: The pattern of cortical thinning-in association with increasing BMI at both midlife and late-life-is consistent with known obesity-related dementia risk. Increased cortical thinning in association with decreasing BMI at late-life may help explain the 'obesity paradox', where high BMI in midlife appears to be a risk factor for dementia, but high BMI in late-life appears, at times, to be protective. PMID- 28993709 TI - The association between BMI and health-related quality of life in the US population: sex, age and ethnicity matters. AB - BACKGROUND: Obesity is a major public health problem. Detailed knowledge about the relationship between body mass index (BMI) and health-related quality of life (HRQL) is important for deriving effective and cost-effective prevention and weight management strategies. This study aims to describe the sex-, age- and ethnicity-specific association between BMI and HRQL in the US adult population. METHODS: Analyses are based on pooled cross-sectional data from 41 459 participants of the Medical Expenditure Panel Survey (MEPS) Household Component (HC) for the years 2000-2003. BMI was calculated using self-reported height and weight, and HRQL was assessed with the EuroQol five-dimensional questionnaire. Generalized additive models were fitted with a smooth function for BMI and a smooth-factor interaction for BMI with sex adjusted for age, ethnicity, poverty, smoking and physical activity. Models were further stratified by age and ethnicity. RESULTS: The association between BMI and HRQL is inverse U-shaped with a HRQL high point at a BMI of 22 kg m-2 in women and a HRQL high plateau at BMI values of 22-30 kg m-2 in men. Men aged 50 years and older with a BMI of 29 kg m 2 reported on average five-point higher visual analog scale (VAS) scores than peers with a BMI of 20 kg m-2. The inverse U-shaped association is more pronounced in older people, and the BMI-HRQL relationship differs between ethnicities. In Hispanics, the BMI associated with the highest HRQL is higher than in white people and, in black women, the BMI-HRQL association has an almost linear negative slope. CONCLUSIONS: The results show that a more differentiated use of BMI cutoffs in scientific discussions and daily practice is indicated. The findings should be considered in the design of future weight loss and weight management programs. PMID- 28993710 TI - Dose-dependent expression of claudin-5 is a modifying factor in schizophrenia. AB - Schizophrenia is a neurodevelopmental disorder that affects up to 1% of the general population. Various genes show associations with schizophrenia and a very weak nominal association with the tight junction protein, claudin-5, has previously been identified. Claudin-5 is expressed in endothelial cells forming part of the blood-brain barrier (BBB). Furthermore, schizophrenia occurs in 30% of individuals with 22q11 deletion syndrome (22q11DS), a population who are haploinsufficient for the claudin-5 gene. Here, we show that a variant in the claudin-5 gene is weakly associated with schizophrenia in 22q11DS, leading to 75% less claudin-5 being expressed in endothelial cells. We also show that targeted adeno-associated virus-mediated suppression of claudin-5 in the mouse brain results in localized BBB disruption and behavioural changes. Using an inducible 'knockdown' mouse model, we further link claudin-5 suppression with psychosis through a distinct behavioural phenotype showing impairments in learning and memory, anxiety-like behaviour and sensorimotor gating. In addition, these animals develop seizures and die after 3-4 weeks of claudin-5 suppression, reinforcing the crucial role of claudin-5 in normal neurological function. Finally, we show that anti-psychotic medications dose-dependently increase claudin-5 expression in vitro and in vivo while aberrant, discontinuous expression of claudin-5 in the brains of schizophrenic patients post mortem was observed compared to age-matched controls. Together, these data suggest that BBB disruption may be a modifying factor in the development of schizophrenia and that drugs directly targeting the BBB may offer new therapeutic opportunities for treating this disorder.Molecular Psychiatry advance online publication, 10 October 2017; doi:10.1038/mp.2017.156. PMID- 28993711 TI - Social impairments in autism spectrum disorder are related to maternal immune history profile. AB - Maternal immune activation has been highlighted as a factor that might increase the risk and severity of autism spectrum disorder (ASD) in children. Preclinical animal evidence shows that immune activation in mothers during pregnancy causes ASD-like behavioural traits in offspring. To this point, there has been no investigation of whether immune system activation in human mothers during pregnancy is associated with more severe symptoms in children with ASD. In this study, data from an existing ASD cohort (N=220) were analysed to investigate whether immune conditions in the mother were associated with greater severity of autism-related symptoms. Results showed that children whose mothers reported a history of immune activation (allergies and asthma) had significantly higher scores on the Social Responsiveness Scale (SRS; P=0.016), suggesting more severe social impairment symptoms in these children. This increasing severity of social impairment symptoms was further shown on the SRS cognition (P=0.007) and mannerisms (P=0.002) subscales. While immune history was associated with an increase in the severity of social impairment symptoms, history of autoimmune conditions in the mother did not have any effect in this cohort. To the best of our knowledge, this study is the first to show an association between immune activation history in the mother and increased ASD symptom severity in children with ASD. These findings support the idea of an immune system-mediated subtype in ASD, where the immune history of the mother may be an important factor. PMID- 28993712 TI - Reversing the amyloid trend: Mechanism of fibril assembly and dissolution of the repeat domain from a human functional amyloid. AB - Amyloids are traditionally observed in the context of disease. However, there is growing momentum that these structures can serve a beneficial role where the amyloid carries out a specific function. These so called 'functional amyloids' have all the structural hallmarks of disease-associated amyloids, raising the question as to what differentiates a well-behaved benign amyloid from a lethally destructive one. Here, we review our work on the repeat domain (RPT) from Pmel17, an important functional amyloid involved in melanin biosynthesis. Particularly, we focused our attention on the unique reversible aggregation-disaggregation process of RPT that is controlled strictly by solution pH. This pH dependence of RPT amyloid formation functions as a switch to control fibril assembly and maintains the benign nature that is associated with functional amyloids. PMID- 28993713 TI - Synthesis of pH indicators for Cerenkov imaging by electrophilic substitution of bromine by fluorine in an aromatic system. AB - Direct electrophilic fluorination using molecular fluorine gas is used in organic synthesis to create novel fluorine-containing compounds with potential beneficial activity that could not be obtained by nucleophilic substitution. In this paper, we report a novel electrophilic substitution of bromine by fluorine in an aromatic system. The mechanism of this type of fluorination was explored using the reaction between bromothymolsulfonphthalein (Bromothymol Blue) and dilute fluorine gas under acidic conditions. Substitution occurs in the bromine atoms located in the ortho-position relative to the hydroxyl group. A similar electrophilic fluorination of thymolsulfonphthalein (Thymol Blue) leads to a substitution of hydrogen atoms in the same position (ortho to hydroxyl). NMR spectroscopy was used to confirm the fluorination sites. NMR spectra of thymolsulfonphthalein and its derivatives under basic conditions can be explained by considering the absence of resonance between the two phenolic rings. Both dibromothymol blue and fluorobromothymol blue revealed intermolecular attenuate Cerenkov radiation selectively near their maximum absorbance in a pH dependent manner. PMID- 28993714 TI - Consequences of Partner Incarceration for Women's Employment. AB - Research has documented the limited opportunities men have to earn income while in prison and the barriers to securing employment and decent wages upon release. However, little research has considered the relationship between men's incarceration and the employment of the women in their lives. Economic theory suggests that family members of incarcerated individuals may attempt to smooth income fluctuation resulting from incarceration by increasing their labor supply. This study used data from the Fragile Families and Child Wellbeing Study (N = 3,780) to investigate how men's incarceration is associated with the number of hours their female partners work as well as variation in this association. Results showed that, on average, women's hours of work were not significantly impacted by the incarceration of their partners. However, there was a positive relationship between partner incarceration and employment among more advantaged groups of women (e.g., married women, white women). PMID- 28993715 TI - Online Social Support for Young People: Does It Recapitulate In-person Social Support; Can It Help? AB - As social media websites have grown in popularity, public concern about online victimization has grown as well; however, much less attention has focused on the possible beneficial effects of online social networks. If theory and research about in-person social networks pertain, then online social relationships may represent an important modern source of or vehicle for support. In a study of 231 undergraduates, three major findings emerged: (1) for people with weaker in person social support, social media sites provide a source of social support that is less redundant of the social support they receive in person; (2) in ways that were not redundant of each other, both online and in-person social support were associated with lower levels of depression-related thoughts and feelings, and (3) the beneficial effects of online social support (like in-person social support) offset some of the adverse effects of peer victimization. The study suggests that augmenting social relations via strategic use of social media can enhance young people's social support systems in beneficial ways. PMID- 28993716 TI - Latent-level relations between DSM-5 PTSD symptom clusters and problematic smartphone use. AB - Common mental health consequences following the experience of potentially traumatic events include Posttraumatic Stress Disorder (PTSD) and addictive behaviors. Problematic smartphone use is a newer manifestation of addictive behaviors. People with anxiety severity (such as PTSD) may be at risk for problematic smartphone use as a means of coping with their symptoms. Unique to our knowledge, we assessed relations between PTSD symptom clusters and problematic smartphone use. Participants (N = 347), recruited through Amazon's Mechanical Turk (MTurk), completed measures of PTSD and smartphone addiction. Results of the Wald tests of parameter constraints indicated that problematic smartphone use was more related to PTSD's negative alterations in cognitions and mood (NACM) than to PTSD's avoidance factor, Wald chi2(1, N = 347) = 12.51, p = 0.0004; and more to PTSD's arousal compared to PTSD's avoidance factor, Wald chi2(1, N = 347) = 14.89, p = 0.0001. Results indicate that problematic smartphone use is most associated with negative affect and arousal among trauma exposed individuals. Implications include the need to clinically assess problematic smartphone use among trauma-exposed individuals presenting with higher NACM and arousal severity; and targeting NACM and arousal symptoms to mitigate the effects of problematic smartphone use. PMID- 28993717 TI - Plasticity may change inputs as well as processes, structures, and responses. AB - Significant work has documented neuroplasticity in development, demonstrating that developmental pathways are shaped by experience. Plasticity is often discussed in terms of the results of differences in input; differences in brain structures, processes, or responses reflect differences in experience. In this paper, I discuss how developmental plasticity also effectively changes input into the system. That is, structures and processes change in response to input, and those changed structures and processes influence future inputs. For example, plasticity may change the pattern of eye movements to a stimulus, thereby changing which part of the scene becomes the input. Thus, plasticity is not only seen in the structures and processes that result from differences in experience, but also is seen in the changes in the input as those structures and processes adapt. The systematic study of the nature of experience, and how differences in experience shape learning, can contribute to our understanding of neuroplasticity in general. PMID- 28993719 TI - The prevalence and marketing of electronic cigarettes in proximity to at-risk youths: An investigation of point-of-sale practices near alternative high schools. AB - This study examines the point-of-sale marketing practices used to promote electronic cigarettes at stores near schools that serve at-risk youth. One hundred stores selling tobacco products within a half mile of alternative high schools in Southern California were assessed for this study. Seventy percent of stores in the sample sold electronic cigarettes. Convenience stores heavily frequented by youth had the highest number of interior ads for e-cigarettes and were the most likely to employ in-store product placement strategies. Increased exposure to the promotion of these products at the point-of-sale poses a challenge for anti-smoking efforts directed toward vulnerable populations. PMID- 28993718 TI - Substituent Effects on Carbon Acidity in Aqueous Solution and at Enzyme Active Sites. AB - Methods are described for the determination of pKas for weak carbon acids in water. The application of these methods to the determination of the pKas for a variety of carbon acids including nitriles, imidazolium cations, amino acids, peptides and their derivatives and, alpha-iminium cations is presented. The substituent effects on the acidity of these different classes of carbon acids are discussed; and, the relevance of these results to catalysis of the deprotonation of amino acids by enzymes and by pyridoxal 5'-phosphate is reviewed. The procedure for estimating the pKa of uridine 5'-phosphate for C-6 deprotonation at the active site of orotidine 5'-phosphate decarboxylase is described, and the effect of a 5-F substituent on carbon acidity of the enzyme-bound substrate is discussed. PMID- 28993720 TI - Visions of the Life Course: Risks, Resources, and Vulnerability. AB - Life course studies have ushered in unprecedented scientific interest not only in specific periods of human lives but also in the long-term processes associated with growing older. Studies that link periods of the life course have identified important sources of continuity and discontinuity and highlighted the antecedents of misfortune. Theories and conceptual frameworks have emerged to help scholars splice pieces of the life course together, but the need for conceptual clarity remains. Concepts such as vulnerability and disadvantage are important but used in many different ways by researchers. We pose questions to enhance clarity of these and related terms and call for greater attention to temporal referents in studying the life course. The attention to chronological time-manifest in the identification of age, period, and cohort-is excellent but greater attention to perceptions of time also is needed to better integrate human agency and historical context in studies of life course processes. PMID- 28993721 TI - Team Clinic: An Innovative Group Care Model for Youth with Type 1 Diabetes Engaging Patients and Meeting Educational Needs. AB - The purpose of this pilot was to implement an innovative group care model, "Team Clinic", for adolescents with type 1 diabetes and assess patient and provider perspectives. Ninety-one intervention patients and 87 controls were enrolled. Ninety-six percent of intervention adolescents endorsed increased support and perceived connecting with peers as important. The medical providers and staff also provided positive feedback stating Team Clinic allowed more creativity in education and higher quality of care. Team Clinic may be a promising model to engage adolescents and incorporate education and support into clinic visits in a format valued by patients and providers. PMID- 28993722 TI - Type 1 Diabetes and Impaired Awareness of Hypoglycemia Are Associated with Reduced Brain Gray Matter Volumes. AB - In this study, we retrospectively analyzed the anatomical MRI data acquired from 52 subjects with type 1 diabetes (26M/26F, 36 +/- 11 years old, A1C = 7.2 +/- 0.9%) and 50 age, sex and BMI frequency-matched non-diabetic controls (25M/25F, 36 +/- 14 years old). The T1D group was further sub-divided based on whether subjects had normal, impaired, or indeterminate awareness of hypoglycemia (n = 31, 20, and 1, respectively). Our goals were to test whether the gray matter (GM) volumes of selected brain regions were associated with diabetes status as well as with the status of hypoglycemia awareness. T1D subjects were found to have slightly smaller volume of the whole cortex as compared to controls (-2.7%, p = 0.016), with the most affected brain region being the frontal lobe (-3.6%, p = 0.024). Similar differences of even larger magnitude were observed among the T1D subjects based on their hypoglycemia awareness status. Indeed, compared to the patients with normal awareness of hypoglycemia, patients with impaired awareness had smaller volume of the whole cortex (-7.9%, p = 0.0009), and in particular of the frontal lobe (-9.1%, p = 0.006), parietal lobe (-8.0%, p = 0.015) and temporal lobe (-8.2%, p = 0.009). Such differences were very similar to those observed between patients with impaired awareness and controls (-7.6%, p = 0.0002 in whole cortex, -9.1%, p = 0.0003 in frontal lobe, -7.8%, p = 0.002 in parietal lobe, and -6.4%, p = 0.019 in temporal lobe). On the other hand, patients with normal awareness did not present significant volume differences compared to controls. No group-differences were observed in the occipital lobe or in the anterior cingulate, posterior cingulate, hippocampus, and thalamus. We conclude that diabetes status is associated with a small but statistically significant reduction of the whole cortex volume, mainly in the frontal lobe. The most prominent structural effects occurred in patients with impaired awareness of hypoglycemia (IAH) as compared to those with normal awareness, perhaps due to the long-term exposure to recurrent episodes of hypoglycemia. Future studies aimed at quantifying relationships of structural outcomes with functional outcomes, with cognitive performance, as well as with parameters describing glucose variability and severity of hypoglycemia episodes, will be necessary to further understand the impact of T1D on the brain. PMID- 28993724 TI - PLPP/CIN Regulates Seizure Activity by the Differential Modulation of Calsenilin Binding to GluN1 and Kv4.2 in Mice. AB - Calsenilin (CSEN) binds to Kv4.2 (an A-type K+ channel) as well as N-methyl-D aspartate receptor (NMDAR), and modulates their activities. However, the regulatory mechanisms for CSEN-binding to Kv4.2 or NMDAR remain elusive. Here, we demonstrate the novel role of pyridoxal-5'-phosphate phosphatase/chronophin (PLPP/CIN), one of the cofilin-mediated F-actin regulators, in the CSEN binding to Kv4.2 or GluN1 (an NMDAR subunit). PLPP/CIN dephosphorylated CSEN in competition with casein kinase 1, independent of cofilin dephosphorylation. As compared to wild-type mice, PLPP/CIN transgenic (PLPP/CINTg) mice showed the enhancement of Kv4.2-CSEN binding, but the reduction in CSEN-GluN1 binding. In addition, PLPP/CINTg mice exhibited the higher intensity (severity), duration and progression of seizures, but the longer latency of seizure on-set in response to kainic acid. PLPP/CIN knockout mice reversed these phenomena. Therefore, we suggest that PLPP/CIN-mediated CSEN dephosphorylation may play an important role in the functional coupling of NMDAR and Kv4.2, which regulates the neuronal excitability. PMID- 28993723 TI - BACE1-Dependent Neuregulin-1 Signaling: An Implication for Schizophrenia. AB - Schizophrenia is a chronic psychiatric disorder with a lifetime prevalence of about 1% in the general population. Recent studies have shown that Neuregulin-1 (Nrg1) is a candidate gene for schizophrenia. At least 15 alternative splicing of NRG1 isoforms all contain an extracellular epidermal growth factor (EGF)-like domain, which is sufficient for Nrg1 biological activity including the formation of myelin sheaths and the regulation of synaptic plasticity. It is known that Nrg1 can be cleaved by beta-secretase (BACE1) and the resulting N-terminal fragment (Nrg1-ntf) binds to receptor tyrosine kinase ErbB4, which activates Nrg1/ErbB4 signaling. While changes in Nrg1 expression levels in schizophrenia still remain controversial, understanding the BACE1-cleaved Nrg1-ntf and Nrg1/ErbB4 signaling in schizophrenia neuropathogenesis is essential and important. In this review paper, we included three major parts: (1) Nrg1 structure and cleavage pattern by BACE1; (2) BACE1-dependent Nrg1 cleavage associated with schizophrenia in human studies; and (3) Animal studies of Nrg1 and BACE1 mutations with behavioral observations. Our review will provide a better understanding of Nrg1 in schizophrenia and a potential strategy for using BACE1 cleavage of Nrg1 as a unique biomarker for diagnosis, as well as a new therapeutic target, of schizophrenia. PMID- 28993725 TI - Laser Speckle Imaging of Rat Pial Microvasculature during Hypoperfusion Reperfusion Damage. AB - The present study was aimed to in vivo assess the blood flow oscillatory patterns in rat pial microvessels during 30 min bilateral common carotid artery occlusion (BCCAO) and 60 min reperfusion by laser speckle imaging (LSI). Pial microcirculation was visualized by fluorescence microscopy. The blood flow oscillations of single microvessels were recorded by LSI; spectral analysis was performed by Wavelet transform. Under baseline conditions, arterioles and venules were characterized by blood flow oscillations in the frequency ranges 0.005 0.0095 Hz, 0.0095-0.021 Hz, 0.021-0.052 Hz, 0.052-0.150 Hz and 0.150-0.500 Hz. Arterioles showed oscillations with the highest spectral density when compared with venules. Moreover, the frequency components in the ranges 0.052-0.150 Hz and 0.150-0.500 were predominant in the arteriolar total power spectrum; while, the frequency component in the range 0.150-0.500 Hz showed the highest spectral density in venules. After 30 min BCCAO, the arteriolar spectral density decreased compared to baseline; moreover, the arteriolar frequency component in the range 0.052-0.150 Hz significantly decreased in percent spectral density, while the frequency component in the range 0.150-0.500 Hz significantly increased in percent spectral density. However, an increase in arteriolar spectral density was detected at 60 min reperfusion compared to BCCAO values; consequently, an increase in percent spectral density of the frequency component in the range 0.052-0.150 Hz was observed, while the percent spectral density of the frequency component in the range 0.150-0.500 Hz significantly decreased. The remaining frequency components did not significantly change during hypoperfusion and reperfusion. The changes in blood flow during hypoperfusion/reperfusion caused tissue damage in the cortex and striatum of all animals. In conclusion, our data demonstrate that the frequency component in the range 0.052-0.150 Hz, related to myogenic activity, was significantly impaired by hypoperfusion and reperfusion, affecting cerebral blood flow distribution and causing tissue damage. PMID- 28993726 TI - Pavlovian Extinction and Recovery Effects in Aversive Pavlovian to Instrumental Transfer. AB - Three studies explored the sensitivity of aversive Pavlovian to instrumental transfer (PIT) to Pavlovian extinction in rodents. Rats underwent Pavlovian conditioning prior to avoidance training. The PIT test then involved assessment of the effects of the Pavlovian conditioned stimulus (CS) on the performance of the avoidance response (AR). Conducting extinction prior to avoidance training and transfer testing, allowed spontaneous recovery and shock reinstatement of extinguished motivation, whereas conducting extinction following avoidance training and just prior to PIT testing successfully reduced transfer effects. This was also the case in a design that compared responding to an extinguished CS against a non-extinguished CS rather than comparing extinguished and non extinguished groups to one another. While extinction treatments in many appetitive PIT studies do not successfully reduce transfer, and can sometimes enhance the effect, the current findings show that an extinction treatment temporally close to transfer testing can reduce the motivational impact of the aversive Pavlovian CS on instrumental avoidance responding. PMID- 28993727 TI - Pain Processing in a Social Context and the Link with Psychopathic Personality Traits-An Event-Related Potential Study. AB - Empathy describes the ability to understand another person's feelings. Psychopathy is a disorder that is characterized by a lack of empathy. Therefore, empathy and psychopathy are interesting traits to investigate with respect to experiencing and observing pain. The present study aimed to investigate pain empathy and pain sensitivity by measuring event-related potentials (ERPs) extracted from the ongoing EEG in an interactive setup. Each participant fulfilled subsequently the role of "villain" and "victim". In addition, mode of control was modulated resulting in four different conditions; passive villain, active villain, active victim and passive victim. Response-, visual- and pain ERPs were compared between the four conditions. Furthermore, the role of psychopathic traits in these outcomes was investigated. Our findings suggested that people experience more conflict when hurting someone else than hurting themselves. Furthermore, our results indicated that self-controlled pain was experienced as more painful than uncontrolled pain. People that scored high on psychopathic traits seemed to process and experience pain differently. According to the results of the current study, social context, attention and personality traits seem to modulate pain processing and the empathic response to pain in self and others. The within-subject experimental design described here provides an excellent approach to further unravel the influence of social context and personality traits on social cognition. PMID- 28993728 TI - Age Drives Distortion of Brain Metabolic, Vascular and Cognitive Functions, and the Gut Microbiome. AB - Advancing age is the top risk factor for the development of neurodegenerative disorders, including Alzheimer's disease (AD). However, the contribution of aging processes to AD etiology remains unclear. Emerging evidence shows that reduced brain metabolic and vascular functions occur decades before the onset of cognitive impairments, and these reductions are highly associated with low-grade, chronic inflammation developed in the brain over time. Interestingly, recent findings suggest that the gut microbiota may also play a critical role in modulating immune responses in the brain via the brain-gut axis. In this study, our goal was to identify associations between deleterious changes in brain metabolism, cerebral blood flow (CBF), gut microbiome and cognition in aging, and potential implications for AD development. We conducted our study with a group of young mice (5-6 months of age) and compared those to old mice (18-20 months of age) by utilizing metabolic profiling, neuroimaging, gut microbiome analysis, behavioral assessments and biochemical assays. We found that compared to young mice, old mice had significantly increased levels of numerous amino acids and fatty acids that are highly associated with inflammation and AD biomarkers. In the gut microbiome analyses, we found that old mice had increased Firmicutes/Bacteroidetes ratio and alpha diversity. We also found impaired blood brain barrier (BBB) function and reduced CBF as well as compromised learning and memory and increased anxiety, clinical symptoms often seen in AD patients, in old mice. Our study suggests that the aging process involves deleterious changes in brain metabolic, vascular and cognitive functions, and gut microbiome structure and diversity, all which may lead to inflammation and thus increase the risk for AD. Future studies conducting comprehensive and integrative characterization of brain aging, including crosstalk with peripheral systems and factors, will be necessary to define the mechanisms underlying the shift from normal aging to pathological processes in the etiology of AD. PMID- 28993730 TI - Molecular Guided Therapy Provides Sustained Clinical Response in Refractory Choroid Plexus Carcinoma. AB - Choroid plexus carcinomas (CPCs) are rare, aggressive pediatric brain tumors with no established curative therapy for relapsed disease, and poor survival rates. TP53 Mutation or dysfunction correlates with poor or no survival outcome in CPCs. Here, we report the case of a 4 month-old female who presented with disseminated CPC. After initial response to tumor resection and adjuvant-chemotherapy, the tumor recurred and metastasized with no response to aggressive relapse therapy suggesting genetic predisposition. This patient was then enrolled to a Molecular Guided Therapy Clinical Trial. Genomic profiling of patient tumor and normal sample identified a TP53 germline mutation with loss of heterozygosity, somatic mutations including IDH2, and aberrant activation of biological pathways. The mutations were not targetable for therapy. However, targeting the altered biological pathways (mTOR, PDGFRB, FGF2, HDAC) guided identification of possibly beneficial treatment with a combination of sirolimus, thalidomide, sunitinib, and vorinostat. This therapy led to 92% reduction in tumor size with no serious adverse events, excellent quality of life and long term survival. PMID- 28993729 TI - Differential Impact of Single-Dose Fe Ion and X-Ray Irradiation on Endothelial Cell Transcriptomic and Proteomic Responses. AB - Background and Purpose: Radiotherapy is an essential tool for cancer treatment. In order to spare normal tissues and to reduce the risk of normal tissue complications, particle therapy is a method of choice. Although a large part of healthy tissues can be spared due to improved depth dose characteristics, little is known about the biological and molecular mechanisms altered after particle irradiation in healthy tissues. Elucidation of these effects is also required in the context of long term space flights, as particle radiation is the main contributor to the radiation effects observed in space. Endothelial cells (EC), forming the inner layer of all vascular structures, are especially sensitive to irradiation and, if damaged, contribute to radiation-induced cardiovascular disease. Materials and Methods: Transcriptomics, proteomics and cytokine analyses were used to compare the response of ECs irradiated or not with a single 2 Gy dose of X-rays or Fe ions measured one and 7 days post-irradiation. To support the observed inflammatory effects, monocyte adhesion on ECs was also assessed. Results: Experimental data indicate time- and radiation quality-dependent changes of the EC response to irradiation. The irradiation impact was more pronounced and longer lasting for Fe ions than for X-rays. Both radiation qualities decreased the expression of genes involved in cell-cell adhesion and enhanced the expression of proteins involved in caveolar mediated endocytosis signaling. Endothelial inflammation and adhesiveness were increased with X-rays, but decreased after Fe ion exposure. Conclusions: Fe ions induce pro-atherosclerotic processes in ECs that are different in nature and kinetics than those induced by X-rays, highlighting radiation quality-dependent differences which can be linked to the induction and progression of cardiovascular diseases (CVD). Our findings give a better understanding of the underlying processes triggered by particle irradiation in ECs, a crucial aspect for the development of protective measures for cancer patients undergoing particle therapy and for astronauts in space. PMID- 28993731 TI - Small and Intermediate Calcium-Activated Potassium Channel Openers Improve Rat Endothelial and Erectile Function. AB - Modulation of endothelial calcium-activated potassium (KCa) channels has been proposed as an approach to restore endothelial function. The present study investigated whether novel openers of KCa channels with small (KCa2.x) and intermediate (KCa3.1) conductance, NS309 and NS4591, improve endothelium dependent relaxation and erectile function. Rat corpus cavernosum (CC) strips were mounted for isometric tension recording and processed for immunoblotting. Mean arterial pressure (MAP), intracavernosal pressure (ICP), and electrocardiographic (ECG) measurements were conducted in anesthetized rats. Immunoblotting revealed the presence of KCa2.3 and large KCa conductance (KCa1.1) channels in the corpus cavernosum. NS309 and NS4591 increased current in CC endothelial cells in whole cell patch clamp experiments. Relaxation induced by NS309 (<1 MUM) was inhibited by endothelial cell removal and high extracellular potassium. An inhibitor of nitric oxide (NO) synthase, and blockers of KCa2.x and KCa1.1 channels, apamin and iberiotoxin also inhibited NS309 relaxation. Incubation with NS309 (0.5 MUM) markedly enhanced acetylcholine relaxation. Basal erectile function (ICP/MAP) increased during administration of NS309. Increases in ICP/MAP after cavernous nerve stimulation with NS309 were unchanged, whereas NS4591 significantly improved erectile function. Administration of NS309 and NS4591 caused small changes in the electrocardiogram, but neither arrhythmic events nor prolongation of the QTc interval were observed. The present study suggests that openers of KCa2.x and KCa3.1 channels improve endothelial and erectile function. The effects of NS309 and NS4591 on heart rate and ECG are small, but will require additional safety studies before evaluating whether activation of KCa2.3 channels has a potential for treatment of erectile dysfunction. PMID- 28993733 TI - LncRNA-uc002mbe.2 Interacting with hnRNPA2B1 Mediates AKT Deactivation and p21 Up Regulation Induced by Trichostatin in Liver Cancer Cells. AB - Long non-coding RNAs (lncRNAs) have been implicated in liver carcinogenesis. We previously showed that the induction of lncRNA-uc002mbe.2 is positively associated with the apoptotic effect of trichostatin A (TSA) in hepatocellular carcinoma (HCC) cells. The current study further analyzed the role of uc002mbe.2 in TSA-induced liver cancer cell death. The level of uc002mbe.2 was markedly increased by TSA in the cytoplasm of HCC cells. Knockdown of uc002mbe.2 prohibited TSA-induced G2/M cell cycle arrest, p21 induction, and apoptosis of Huh7 cells and reversed the TSA-mediated decrease in p-AKT. RNA pull-down and RNA binding protein immunoprecipitation (RIP) assays revealed that TSA induced an interaction between uc002mbe.2 and heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) in Huh7 cells. This interaction mediated AKT deactivation and p21 induction in liver cancer cells. In an athymic xenograft mouse model, knockdown of uc002mbe.2 significantly prohibited the TSA-mediated reduction in tumor size and weight. In addition, the ability of TSA to reduce hnRNPA2B1 and p-AKT levels and induce p21 in the xenograft tumors was prevented by uc002mbe.2 knockdown. Therefore, the interaction of uc002mbe.2 and hnRNPA2B1 in mediating AKT deactivation and p21 induction is involved in the cytostatic effect of trichostatin in liver cancer cells. PMID- 28993734 TI - Osmotin Protects H9c2 Cells from Simulated Ischemia-Reperfusion Injury through AdipoR1/PI3K/AKT Signaling Pathway. AB - Objective: This study aimed to investigate the effect of osmotin on myocardial ischemia/reperfusion (I/R), as well as the underlying mechanisms. Methods:In vitro I/R injury model was established on rat cardiac myoblast H9c2 cells by oxygen and glucose deprivation followed by reperfusion (OGD/R). Cells were administrated with osmotin, and transfected with small interfering RNAs (siRNAs) which specifically target adiponectin receptor 1 or 2 (AdipoR1/2). Besides, the cells were incubated with or without LY294002 as inhibitor of phosphatidylinositol 3-kinase (PI3K) under OGD/R condition. Cell viability, apoptosis, expressions of apoptosis-related proteins and inflammatory factors were analyzed. Results: The results showed that osmotin significantly increased H9c2 cells viability compared with the cells treated with vehicle (P < 0.05), and decreased H9c2 cells apoptosis by regulating expressions of apoptosis-related proteins. Moreover, we observed that osmotin statistically reduced the release of proinflammatory factors and increased the release of anti-inflammatory factors in H9c2 cells (P < 0.05). However, these effects were markedly reversed by AdipoR1 silence but not AdipoR2. Furthermore, osmotin dramatically upregulated the phosphorylation levels of PI3K, AKT, ERK, and downregulated the phosphorylation level of NF-kappaB (P < 0.05). While administration of LY294002 reduced cell viability, increased cell apoptosis, and aggravated inflammatory response (P < 0.05). Conclusion: Our results suggested that the protective effect of osmotin on the simulated OGD/R injured H9c2 cells might be associated with AdipoR1/PI3K/AKT signaling pathway. PMID- 28993735 TI - Comparative Physiological, Biochemical, and Genetic Responses to Prolonged Waterlogging Stress in Okra and Maize Given Exogenous Ethylene Priming. AB - Waterlogging is an environmental challenge affecting crops worldwide. Ethylene induces the expression of genes linked to important agronomic traits under waterlogged conditions. The ability of okra (Abelmoschus esculentus L. Moench.) and maize (Zea mays L.) given exogenous ethylene priming to tolerate prolonged waterlogged conditions was investigated in this study. The investigation was carried out as field experiments using 3 week-old plants grouped into four treatments; control, waterlogged plants, ethylene priming of plants before waterlogging, and ethylene priming of plants after waterlogging. Different growth parameters were recorded. Soil chemical and bacterial analyses were performed. The activity and gene expression of antioxidant enzymes were studied. The ethylene biosynthetic genes expression analysis and root anatomy of surviving okra plants were also carried out. Results revealed that okra and maize plants showed increase in their height under waterlogged conditions. Ethylene priming and waterlogged conditions induced early production of adventitious roots in okra and maize. Maize survival lasted between 5 and 9 weeks under waterlogging without reaching the flowering stage. However, okra survived up to 15 weeks under waterlogging producing flower buds and fruits in all treatments. Variable changes were also recorded for total soluble phenolics of soil. Cross sections of waterlogged okra roots showed the formation of a dark peripheral layer and numerous large aerenchyma cells which may have assisted in trapping oxygen required for survival. The activity and gene expression levels of antioxidant enzymes were studied and showed higher increases in the root and leaf tissues of okra and maize subjected to both waterlogging and ethylene priming, as compared to control or waterlogged condition. Quantitative RT-PCR analysis also showed that the ethylene biosynthetic gene expression levels in all okra and maize tissues were up-regulated and showed much higher levels under ethylene-treated waterlogged conditions than those expressed under control or waterlogged conditions at all time points. These results indicate that okra and maize tissues respond to the conditions of waterlogging and exogenous ethylene priming by inducing their ethylene biosynthetic genes expression in order to enhance ethylene production and tolerate the prolonged waterlogging stress. In conclusion, this study revealed that exogenously generated ethylene gas as a priming treatment before or after waterlogging could enhance waterlogging tolerance in maize and okra crops. PMID- 28993737 TI - Current Trends and Research Challenges Regarding "Preparation for Oxidative Stress". AB - Survival under stress, such as exposure to hypoxia, anoxia, freezing, dehydration, air exposure of water breathing organisms, and estivation, is commonly associated to enhanced endogenous antioxidants, a phenomenon coined "preparation for oxidative stress" (POS). The regulation of free radical metabolism seems to be crucial under these selective pressures, since this response is widespread among animals. A hypothesis of how POS works at the molecular level was recently proposed and relies on two main processes: increased reactive species production under hypoxia, and activation of redox-sensitive transcription factors and signaling pathways, increasing the expression of antioxidants. The present paper brings together the current knowledge on POS and considers its future directions. Data indicate the presence of POS in 83 animal species (71.6% among investigated species), distributed in eight animal phyla. Three main research challenges on POS are presented: (i) to identify the molecular mechanism(s) that mediate/induce POS, (ii) to identify the evolutionary origins of POS in animals, and (iii) to determine the presence of POS in natural environments. We firstly discuss the need of evidence for increased RS production in hypoxic conditions that underlie the POS response. Secondly, we discuss the phylogenetic origins of POS back 700 million years, by identifying POS-positive responses in cnidarians. Finally, we present the first reports of the POS adaptation strategy in the wild. The investigation of these research trends and challenges may prove useful to understand the evolution of animal redox adaptations and how they adapt to increasing stressful environments on Earth. PMID- 28993736 TI - Pathogenic Mechanisms of Bicuspid Aortic Valve Aortopathy. AB - Bicuspid aortic valve (BAV) is the most common congenital valvular defect and is associated with ascending aortic dilation (AAD) in a quarter of patients. AAD has been ascribed both to the hemodynamic consequences of normally functioning and abnormal BAV morphology, and to the effect of rare and common genetic variation upon function of the ascending aortic media. AAD manifests in two overall and sometimes overlapping phenotypes: that of aortic root aneurysm, similar to the AAD of Marfan syndrome; and that of tubular AAD, similar to the AAD seen with tricuspid aortic valves (TAVs). These aortic phenotypes appear to be independent of BAV phenotype, have different embryologic origins and have unique etiologic factors, notably, regarding the role of hemodynamic changes inherent to the BAV phenotype. Further, in contrast to Marfan syndrome, the AAD seen with BAV is infrequently present as a strongly inherited syndromic phenotype; rather, it appears to be a less-penetrant, milder phenotype. Both reduced levels of normally functioning transcriptional proteins and structurally abnormal proteins have been observed in aneurysmal aortic media. We provide evidence that aortic root AAD has a stronger genetic etiology, sometimes related to identified common non-coding fibrillin-1 (FBN1) variants and other aortic wall protein variants in patients with BAV. In patients with BAV having tubular AAD, we propose a stronger hemodynamic influence, but with pathology still based on a functional deficit of the aortic media, of genetic or epigenetic etiology. Although it is an attractive hypothesis to ascribe common mechanisms to BAV and AAD, thus far the genetic etiologies of AAD have not been associated to the genetic etiologies of BAV, notably, not including BAV variants in NOTCH1 and GATA4. PMID- 28993738 TI - Continuous Release of Tumor-Derived Factors Improves the Modeling of Cachexia in Muscle Cell Culture. AB - Cachexia is strongly associated with a poor prognosis in cancer patients but the biological trigger is unknown and therefore no therapeutics exist. The loss of skeletal muscle is the most deleterious aspect of cachexia and it appears to depend on secretions from tumor cells. Models for studying wasting in cell culture consist of experiments where skeletal muscle cells are incubated with medium conditioned by tumor cells. This has led to candidates for cachectic factors but some of the features of cachexia in vivo are not yet well-modeled in cell culture experiments. Mouse myotube atrophy measured by myotube diameter in response to medium conditioned by mouse colon carcinoma cells (C26) is consistently less than what is seen in muscles of mice bearing C26 tumors with moderate to severe cachexia. One possible reason for this discrepancy is that in vivo the C26 tumor and skeletal muscle share a circulatory system exposing the muscle to tumor factors in a constant and increasing way. We have applied Transwell(r)-adapted cell culture conditions to more closely simulate conditions found in vivo where muscle is exposed to the ongoing kinetics of constant tumor secretion of active factors. C26 cells were incubated on a microporous membrane (a Transwell(r) insert) that constitutes the upper compartment of wells containing plated myotubes. In this model, myotubes are exposed to a constant supply of cancer cell secretions in the medium but without direct contact with the cancer cells, analogous to a shared circulation of muscle and cancer cells in tumor-bearing animals. The results for myotube diameter support the idea that the use of Transwell(r) inserts serves as a more physiological model of the muscle wasting associated with cancer cachexia than the bolus addition of cancer cell conditioned medium. The Transwell(r) model supports the notion that the dose and kinetics of cachectic factor delivery to muscle play a significant role in the extent of pathology. PMID- 28993739 TI - Increased Subjective Distaste and Altered Insula Activity to Umami Tastant in Patients with Bulimia Nervosa. AB - The aim of this study was to examine differences in brain neural activation in response to monosodium glutamate (MSG), the representative component of umami, between patients with bulimia nervosa (BN) and healthy women (HW) controls. We analyzed brain activity after ingestion of an MSG solution using functional magnetic resonance imaging (fMRI) in a group of women with BN (n = 18) and a group of HW participants (n = 18). Both groups also provided a subjective assessment of the MSG solution via a numerical rating scale. The BN group subjectively rated the MSG solution lower in pleasantness and liking than the control group, although no difference in subjective intensity was noted. The fMRI results demonstrated greater activation of the right insula in the BN group versus the control group. Compared with the HW controls, the BN patients demonstrated both altered taste perception-related brain activity and more negative hedonic scores in response to MSG stimuli. Different hedonic evaluation, expressed as the relative low pleasing taste of umami tastant and associated with altered insula function, may explain disturbed eating behaviors, including the imbalance in food choices, in BN patients. PMID- 28993740 TI - Pharmacological Augmentation of Psychosocial and Remediation Training Efforts in Schizophrenia. AB - Pharmacological approaches to cognitive enhancement have received considerable attention but have not had considerable success in improving their cognitive and functional targets. Other intervention strategies, such as cognitive remediation therapy (CRT), have been shown to enhance cognitive performance but have not been found to improve functional outcomes without additional psychosocial interventions. Recently, several studies have attempted to enhance the effects of CRT by adding pharmacological interventions to the CRT treatments. In addition, as CRT has been shown to synergistically improve the effects of psychosocial interventions, the combination of pharmacological therapies aimed at cognition and psychosocial interventions may itself provide a promising strategy for improving functional outcomes. This review and commentary examines the current state of interventions combining CRT and psychosocial treatments with pharmacological augmentation. Our focus is on the specific level of effect of the pharmacological intervention, which could be enhancing motivation, training efficiency, or the consolidation of therapeutic gains. Different pharmacological strategies (e.g., stimulants, plasticity-inducing agents, or attentional or alertness enhancers) may have the potential to lead to different types of gains when combined with CRT or psychosocial interventions. The relative potential of these different mechanisms for immediate and durable effects is considered. PMID- 28993741 TI - Executive Control and Striatal Resting-State Network Interact with Risk Factors to Influence Treatment Outcomes in Alcohol-Use Disorder. AB - Alterations within mesocorticolimbic terminal regions commonly occur with alcohol use disorder (AUD). As pathological drug-seeking behavior may arise as a consequence of alcohol-induced neuroadaptations, it is critical to understand how such changes increase the likelihood of relapse. This report examined resting state functional connectivity (RSFC) using both a seed-based and model-free approach in individuals in treatment for AUD and how dysregulation of network connectivity contributes to treatment outcomes. In order to provide a mechanism by which neural networks promote relapse, interactive effects of mesocorticolimbic connectivity and AUD risk factors in treatment completers and non-completers were examined. AUD group showed stronger RSFC between striatum, insula, and anterior cingulate cortex than controls. Within the AUD group, non completers compared to completers showed enhanced RSFC between (1) striatum insula, (2) executive control network (ECN)-amygdala, and (3) basal ganglia/salience network and striatum, precuneus, and insula. Completers showed enhanced RSFC between striatum-right dorsolateral prefrontal cortex. Furthermore, completers and non-completers differed in relationships between RSFC and relapse risk factors, where non-completers exhibited positive associations between craving intensity and RSFC of striatum-insula and ECN-amygdala. These findings provide evidence for interactions between corticolimbic connectivity in AUD and craving and establish an important link between network connectivity and dynamic risk factors that contribute to relapse. Results demonstrate that relapse vulnerability is attributed to craving dysregulation manifested by enhanced connectivity in striato-limbic regions and diminished corticostriatal connectivity. PMID- 28993742 TI - Development and Validation of the Amphetamine-Type Stimulants Motive Questionnaire in a Clinical Population. AB - Approximately 35.7 million people world-wide use amphetamine-type stimulants (ATS) leading to a high demand for effective treatment. Understanding the motives behind ATS use is a necessary basis for preventive and therapeutic treatment. The objective of this study is to develop the Amphetamine-Type stimulants Motive Questionnaire (AMQ) and to confirm its construct and concurrent validity in respect to the first and the latest month of ATS use based on answers of 233 patients with ATS disorders (74.2% male; mean age: 31.1 years). Confirmatory factor analyses were employed to test for the construct validity of the AMQ. Nested models of confirmatory factor analyses with increasing constraints for gender and age were estimated to test the equivalence of the factor structure in different subgroups. Independent sample t-tests were conducted to test for mean differences in the motive dimensions. A structural equation model was estimated to confirm the concurrent validity using the latent four motive factors (i.e., enhancement, coping, social, and conformity motives) as independent variables and frequency of ATS use in the first and the latest month of use as a dependent variable. The results confirmed the AMQ's four-dimensional factor structure in general, and across gender and age groups for both periods of time. Men (first month: M = 4.21, SD = 0.75; latest month: M = 3.86, SD = 0.93) use ATS more frequently due to enhancement motives than women (first month: M = 3.85, SD = 1.12; latest month: M = 3.46, SD = 1.29) at both periods of time [first month: t(77) = -2.33, p = 0.022; latest month: t(80) = -2.19, p = 0.031]. Structural equation modeling confirmed an association between coping motives and use frequency, for both periods of time (first and latest month: beta = 0.32, p < 0.001), as well as between social motives and frequency of use for the latest month of use (beta = 0.30, p < 0.01). To conclude, the AMQ is a valid and reliable instrument for assessing motives of ATS use in a clinical population. It can provide important insights into the motivational structure of the first and latest months of ATS use which are useful for preventive and therapeutic treatments as well as the development of abstinence skills. PMID- 28993743 TI - The Joint Contribution of Activation and Inhibition in Moderating Carryover Effects of Anger on Social Judgment. AB - Carryover effects of emotions that lead to biases in social judgments are commonly observed. We suggest that such effects may be influenced by the ability to engage or disengage attention from emotional stimuli. We assessed the ability to activate and inhibit attention to anger stimuli, experimentally induced anger in a demanding task, and measured social judgment toward an ambiguous target. Results show that higher activation and higher inhibition of anger-related information predicted more biased evaluations of the ambiguous target when individuals were experiencing anger, but not in an emotionally neutral condition. Interestingly, the effect of activation and inhibition in the anger condition emerged only when such variables were entered simultaneously in the regression model, indicating that they had an additive effect in predicting carryover effects of anger on social judgement. Results are consistent with a cooperative suppression effect (Conger, 1974) of activation and inhibition and may be explained by either an increased accessibility of anger-related cues leading to more biased social judgments, or by an instance in which being good at engaging in and disengaging attention from emotional cues might have depleted participants' resources making carryover effects of anger more likely to occur. Ultimately, the finding highlight that individual differences in attentional processes are important moderators for carryover effects of emotions. PMID- 28993744 TI - More Stable Ties or Better Structure? An Examination of the Impact of Co-author Network on Team Knowledge Creation. AB - This study aims to explore the influence of co-author network on team knowledge creation. Integrating the two traditional perspectives of network relationship and network structure, we examine the direct and interactive effects of tie stability and structural holes on team knowledge creation. Tracking scientific articles published by 111 scholars in the research field of human resource management from the top 8 American universities, we analyze scholars' scientific co-author networks. The result indicates that tie stability changes the teams' information processing modes and, when graphed, results in an inverted U-shape relationship between tie stability and team knowledge creation. Moreover, structural holes in co-author network are proved to be harmful to team knowledge sharing and diffusion, thereby impeding team knowledge creation. Also, tie stability and structural hole interactively influence team knowledge creation. When the number of structural hole is low in the co-author network, the graphical representation of the relationship between tie stability and team knowledge creation tends to be a more distinct U-shape. PMID- 28993745 TI - When the Sound Becomes the Goal. 4E Cognition and Teleomusicality in Early Infancy. AB - In this paper we explore early musical behaviors through the lenses of the recently emerged "4E" approach to mind, which sees cognitive processes as Embodied, Embedded, Enacted, and Extended. In doing so, we draw from a range of interdisciplinary research, engaging in critical and constructive discussions with both new findings and existing positions. In particular, we refer to observational research by French pedagogue and psychologist Francois Delalande, who examined infants' first "sound discoveries" and individuated three different musical "conducts" inspired by the "phases of the game" originally postulated by Piaget. Elaborating on such ideas we introduce the notion of "teleomusicality," which describes the goal-directed behaviors infants adopt to explore and play with sounds. This is distinguished from the developmentally earlier "protomusicality," which is based on music-like utterances, movements, and emotionally relevant interactions (e.g., with primary caregivers) that do not entail a primary focus on sound itself. The development from protomusicality to teleomusicality is discussed in terms of an "attentive shift" that occurs between 6 and 10 months of age. This forms the basis of a conceptual framework for early musical development that emphasizes the emergence of exploratory, goal-directed (i.e., sound-oriented), and self-organized musical actions in infancy. In line with this, we provide a preliminary taxonomy of teleomusical processes discussing "Original Teleomusical Acts" (OTAs) and "Constituted Teleomusical Acts" (CTAs). We argue that while OTAs can be easily witnessed in infants' exploratory behaviors, CTAs involve the mastery of more specific and complex goal-directed chains of actions central to musical activity. PMID- 28993746 TI - Rumination as a Mediator between Childhood Trauma and Adulthood Depression/Anxiety in Non-clinical Participants. AB - Objective: Although there is strong evidence that childhood trauma is associated with the development of depression and anxiety, relatively few studies have explored potential mediating factors for this relationship. The present study aimed to evaluate the mediating role of rumination in the link between childhood trauma and mood status such as depression, anxiety and affective lability. Materials and Methods: Two hundred and seven non-clinical participants completed the Childhood Trauma Questionnaire, the Ruminative Response Scale, the Beck Depression Inventory, the State Anxiety Inventory, and the Affective Lability Scale. Structural equation modeling was used to evaluate the results. Results: Our results supported that rumination is a meaningful mediator between childhood trauma and depression/anxiety in non-clinical participants. The mediation model indicated that childhood trauma and its subtypes are linked to depression and anxiety through three subtypes of rumination, thereby supporting a significant indirect relationship (Standardized coefficient [SC] = 0.56, p < 0.001 for the path from trauma to rumination; SC = 0.67, p < 0.001, from rumination to mood). The direct relationship between childhood trauma and mood symptoms was also significant in a model including rumination (SC = 0.68, p < 0.001). The mediation effect of rumination in the relationship between childhood trauma and mood was more predominant in female participants. Conclusions: The present study found that rumination mediates the influence of childhood trauma on the development of mood symptoms in non-clinical participants. Childhood trauma appears to be a critical determinant for developing symptoms of depression and anxiety. PMID- 28993747 TI - The Use of Virtual Reality Facilitates Dialectical Behavior Therapy(r) "Observing Sounds and Visuals" Mindfulness Skills Training Exercises for a Latino Patient with Severe Burns: A Case Study. AB - Sustaining a burn injury increases an individual's risk of developing psychological problems such as generalized anxiety, negative emotions, depression, acute stress disorder, or post-traumatic stress disorder. Despite the growing use of Dialectical Behavioral Therapy(r) (DBT(r)) by clinical psychologists, to date, there are no published studies using standard DBT(r) or DBT(r) skills learning for severe burn patients. The current study explored the feasibility and clinical potential of using Immersive Virtual Reality (VR) enhanced DBT(r) mindfulness skills training to reduce negative emotions and increase positive emotions of a patient with severe burn injuries. The participant was a hospitalized (in house) 21-year-old Spanish speaking Latino male patient being treated for a large (>35% TBSA) severe flame burn injury. Methods: The patient looked into a pair of Oculus Rift DK2 virtual reality goggles to perceive the computer-generated virtual reality illusion of floating down a river, with rocks, boulders, trees, mountains, and clouds, while listening to DBT(r) mindfulness training audios during 4 VR sessions over a 1 month period. Study measures were administered before and after each VR session. Results: As predicted, the patient reported increased positive emotions and decreased negative emotions. The patient also accepted the VR mindfulness treatment technique. He reported the sessions helped him become more comfortable with his emotions and he wanted to keep using mindfulness after returning home. Conclusions: Dialectical Behavioral Therapy is an empirically validated treatment approach that has proved effective with non-burn patient populations for treating many of the psychological problems experienced by severe burn patients. The current case study explored for the first time, the use of immersive virtual reality enhanced DBT(r) mindfulness skills training with a burn patient. The patient reported reductions in negative emotions and increases in positive emotions, after VR DBT(r) mindfulness skills training. Immersive Virtual Reality is becoming widely available to mainstream consumers, and thus has the potential to make this treatment available to a much wider number of patient populations, including severe burn patients. Additional development, and controlled studies are needed. PMID- 28993748 TI - White Matter Correlates of Musical Anhedonia: Implications for Evolution of Music. AB - Recent theoretical advances in the evolution of music posit that affective communication is an evolutionary function of music through which the mind and brain are transformed. A rigorous test of this view should entail examining the neuroanatomical mechanisms for affective communication of music, specifically by comparing individual differences in the general population with a special population who lacks specific affective responses to music. Here we compare white matter connectivity in BW, a case with severe musical anhedonia, with a large sample of control subjects who exhibit normal variability in reward sensitivity to music. We show for the first time that structural connectivity within the reward system can predict individual differences in musical reward in a large population, but specific patterns in connectivity between auditory and reward systems are special in an extreme case of specific musical anhedonia. Results support and extend the Mixed Origins of Music theory by identifying multiple neural pathways through which music might operate as an affective signaling system. PMID- 28993749 TI - When One Shape Does Not Fit All: A Commentary Essay on the Use of Graphs in Psychological Research. PMID- 28993750 TI - The Role of Second-Person Information in the Development of Social Understanding. AB - We consider the second-person or interactive approach to social understanding, conceived as an understanding of intentional relations. We identify five forms of second-person information - self-directedness, contingency, reciprocity, affective engagement, and shared intentions - that occur only in interactions. We assess the extent to which these forms of information are available to observers of interactions as well as to the participants of an interaction and conclude that whereas observers may gain some second-person information, interactive participants have a privileged position. We also ask whether these forms of second-person information can deliver social understanding in terms of the understanding of intentional relations that are descriptive of persons. We argue that whereas none of these forms alone is sufficient for understanding intentional relations, they all play an important role in the developmental processes that enable the construction of social understanding. Therefore, the second-person approach, understood as theorizing how second-person information available in interactions is used in the development of social understanding, is a critically important approach to a full theory of social understanding. PMID- 28993752 TI - Histological Characteristics of Intracranial Atherosclerosis in a Chinese Population: A Postmortem Study. AB - BACKGROUND: Anterior and posterior circulation atherosclerosis differ in vascular risk factors and stroke mechanisms. However, few studies have compared the pathological features between these lesions. Using a series of intracranial artery specimens, we characterized the intracranial atherosclerotic lesions and compared pathological features among different arteries of the intracranial vasculature. METHODS: Intracranial large arteries of 32 consecutively recruited autopsy cases of Chinese adults aged 45 years or older were examined pathologically using routine histology and immunostaining, to characterize the pathological features of the atherosclerotic lesions. We analyzed middle cerebral arteries (MCAs) (both left and right), vertebral arteries (VAs) (side more affected), and basilar arteries (BAs). RESULTS: Progressive atherosclerotic lesions were present in 91(71%) of the 128 arteries examined. Features of complicated plaques were infrequently detected: plaque hemorrhage was encountered in 12%, neovasculature in 12%, lumen thrombi in 13%, macrophage infiltration in 20%, and calcification in 25% of arteries. Luminal narrowing of MCA was the most severe, followed by VA; the BA least stenotic (37 +/- 25 vs. 30 +/- 24 vs. 20 +/- 20%, all p < 0.05). MCA had more eccentric (vs. concentric) plaques than VA (69 vs. 25%, p = 0.003) and BA (69 vs. 38%; p = 0.03). Lumen thrombi were more frequent in BA, and calcification most commonly occurred in VA atherosclerotic lesions. CONCLUSION: Intracranial atherosclerotic plaques were commonly present in this sample, but the lesions generally lacked features of complicated plaques. MCA lesions had demonstrable differences compared with VA and BA lesions. Further studies are needed to determine whether these characteristics indicate a distinctive atherosclerotic phenotype for the intracranial vasculature. PMID- 28993751 TI - Immune Modulation in the Treatment of Amyotrophic Lateral Sclerosis: A Review of Clinical Trials. AB - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the degeneration of motor neurons. Though many molecular and genetic causes are thought to serve as predisposing or disease propagating factors, the underlying pathogenesis of the disease is not known. Recent discoveries have demonstrated the presence of inflammation propagating substrates in the central nervous system of patients afflicted with ALS. Over the past decade, this hypothesis has incited an effort to better understand the role of the immune system in ALS and has led to the trial of several potential immune modulating therapies. Here, we briefly review advances in the role of such therapies. The clinical trials discussed here are currently ongoing or have been concluded at the time of writing. PMID- 28993732 TI - Purinergic Signalling: Therapeutic Developments. AB - Purinergic signalling, i.e., the role of nucleotides as extracellular signalling molecules, was proposed in 1972. However, this concept was not well accepted until the early 1990's when receptor subtypes for purines and pyrimidines were cloned and characterised, which includes four subtypes of the P1 (adenosine) receptor, seven subtypes of P2X ion channel receptors and 8 subtypes of the P2Y G protein-coupled receptor. Early studies were largely concerned with the physiology, pharmacology and biochemistry of purinergic signalling. More recently, the focus has been on the pathophysiology and therapeutic potential. There was early recognition of the use of P1 receptor agonists for the treatment of supraventricular tachycardia and A2A receptor antagonists are promising for the treatment of Parkinson's disease. Clopidogrel, a P2Y12 antagonist, is widely used for the treatment of thrombosis and stroke, blocking P2Y12 receptor-mediated platelet aggregation. Diquafosol, a long acting P2Y2 receptor agonist, is being used for the treatment of dry eye. P2X3 receptor antagonists have been developed that are orally bioavailable and stable in vivo and are currently in clinical trials for the treatment of chronic cough, bladder incontinence, visceral pain and hypertension. Antagonists to P2X7 receptors are being investigated for the treatment of inflammatory disorders, including neurodegenerative diseases. Other investigations are in progress for the use of purinergic agents for the treatment of osteoporosis, myocardial infarction, irritable bowel syndrome, epilepsy, atherosclerosis, depression, autism, diabetes, and cancer. PMID- 28993754 TI - Commentary: The Case for Abandoning Therapeutic Chelation of Copper Ions in Alzheimer's Disease. PMID- 28993753 TI - Electroencephalography in the Diagnosis of Genetic Generalized Epilepsy Syndromes. AB - Genetic generalized epilepsy (GGE) consists of several syndromes diagnosed and classified on the basis of clinical features and electroencephalographic (EEG) abnormalities. The main EEG feature of GGE is bilateral, synchronous, symmetric, and generalized spike-wave complex. Other classic EEG abnormalities are polyspikes, epileptiform K-complexes and sleep spindles, polyspike-wave discharges, occipital intermittent rhythmic delta activity, eye-closure sensitivity, fixation-off sensitivity, and photoparoxysmal response. However, admixed with typical changes, atypical epileptiform discharges are also commonly seen in GGE. There are circadian variations of generalized epileptiform discharges. Sleep, sleep deprivation, hyperventilation, intermittent photic stimulation, eye closure, and fixation-off are often used as activation techniques to increase the diagnostic yield of EEG recordings. Reflex seizure related EEG abnormalities can be elicited by the use of triggers such as cognitive tasks and pattern stimulation during the EEG recording in selected patients. Distinct electrographic abnormalities to help classification can be identified among different electroclinical syndromes. PMID- 28993755 TI - Extracranial Internal Carotid Artery Tortuosity and Body Mass Index. AB - BACKGROUND: Extracranial internal carotid artery (eICA) tortuosity may trigger cerebral ischemia, and body mass index (BMI) is a measure of body mass based on height and weight. The main purpose of this study is to determine the influence of BMI on the tortuosity of eICA. METHODS: A total of 926 carotid artery angiograms were performed in 513 patients, of which 116 cases and matched controls were selected. Arterial tortuosity was defined as simple tortuosity, kinking, or coiling. The severity of tortuosity was measured by tortuosity index, formula: [(actual length/straight-line length - 1) * 100]. RESULTS: BMIs were different between the two groups [tortuosity: 27.06 kg/m2 (SD 2.81 kg/m2) versus none: 23.3 kg/m2 (SD 2.78 kg/m2); p < 0.001]. BMI was independently and significantly associated with eICA tortuosity (odds ratio 1.59; 95% confidence interval, 1.35-1.86; p < 0.001). eICA tortuosity index is linearly associated with BMI (exponential coefficient beta = 1.067, p < 0.001). The optimal predictive threshold of BMI for eICA tortuosity was 25.04 kg/m2. The physiological mechanism underlying the reasons why higher BMI has negative influence on extracranial carotid artery tortuosity may be an intra-abdominal hypertension caused by a much higher amount of body fat stored in visceral adipose tissue. CONCLUSION: Our result reveals a novel role for greater BMI on the presence of eICA tortuosity. For each increase in BMI of 1 kg/m2, there is a corresponding 1.59-fold increase in the risk of developing eICA tortuosity. The severity of eICA tortuosity increases linearly with increased BMI. PMID- 28993756 TI - Trench Foot or Non-Freezing Cold Injury As a Painful Vaso-Neuropathy: Clinical and Skin Biopsy Assessments. AB - BACKGROUND: Trench foot, or non-freezing cold injury (NFCI), results from cold exposure of sufficient severity and duration above freezing point, with consequent sensory and vascular abnormalities which may persist for years. Based on observations of Trench foot in World War II, the condition was described as a vaso-neuropathy. While some reports have documented nerve damage after extreme cold exposure, sensory nerve fibres and vasculature have not been assessed with recent techniques in NFCI. OBJECTIVE: To assess patients with chronic sensory symptoms following cold exposure, in order to diagnose any underlying small fibre neuropathy, and provide insight into mechanisms of the persistent pain and cold hypersensitivity. METHODS: Thirty soldiers with cold exposure and persistent sensory symptoms (>4 months) were assessed with quantitative sensory testing, nerve conduction studies, and skin biopsies. Immunohistochemistry was used to assess intraepidermal (IENF) and subepidermal (SENF) nerve fibres with a range of markers, including the pan-neuronal marker protein gene product 9.5 (PGP 9.5), regenerating fibres with growth-associated protein 43 (GAP43), and nociceptor fibres with transient receptor potential cation channel subfamily V member 1 (TRPV1), sensory neuron-specific receptor (SNSR), and calcitonin gene-related peptide (CGRP). von Willebrand factor (vWF), endothelial nitric oxide synthase (eNOS), and vascular endothelial growth factor (VEGF) were used for assessing blood vessels, and transient receptor potential cation channel, subfamily A member 1 (TRPA1) and P2X purinoceptor 7 (P2X7) for keratinocytes, which regulate nociceptors via release of nerve growth factor. RESULTS: Clinical examination showed pinprick sensation was abnormal in the feet of 20 patients (67%), and between 67 and 83% had abnormalities of thermal thresholds to the different modalities. 7 patients (23%) showed reduced sensory action potential amplitude of plantar nerves. 27 patients (90%) had decreased calf skin PGP 9.5 IENF (p < 0.0001), the remaining 3 patients had decreased nerve markers in subepidermis or foot skin. There were marked increases of all vascular markers (for vWF in calf skin, p < 0.0001), and increased sensory or regenerating SENF (for calf skin, GAP43, p = 0.002). TRPA1 (p = 0.0012) and P2X7 (p < 0.0001) were increased in basal keratinocytes. CONCLUSION: A range of skin biopsy markers and plantar nerve conduction studies are useful objective assessments for the diagnosis of peripheral neuropathy in NFCI. Our results suggest that an increase in blood vessels following tissue ischaemia/hypoxia could be associated with disproportionate and abnormal nerve fibres (irritable nociceptors), and may lead to NFCI as a "painful vaso-neuropathy." PMID- 28993757 TI - Painful and Prolonged Muscle Cramps following Insulin Injections in a Patient with Type 2 Diabetes Mellitus: Revisiting the 1992 Duke Case. AB - A 56-year-old middle-eastern male with a long-standing history of poorly controlled type 2 diabetes mellitus presented to us complaining of severely painful bilateral upper and lower extremity cramps occurring shortly after his rapid-acting insulin analog injection(s). The cramps had started 6 months ago and have been occurring intermittently in non-predictable episodes since then. He had otherwise never experienced any insulin-related adverse reaction(s) before. His cramps are very painful and debilitating, interfering with his daily activities and placing him in a state of constant fear/anxiety of re-experiencing them. This caused him to become non-adherent with his prescribed treatment and poorly compliant with his follow-up regimens. Thorough examination showed a diffuse loss of sensation over the lower limbs. This was subsequently confirmed with a combined electromyography-nerve conduction study which indicated extensive diabetic axonal polyneuropathy. By contrast, lower extremity segmental arterial pressures were negative for peripheral vasculo-occlusive disease, ruling out vascular insufficiency as a possible etiology of the cramps. We then measured the levels of serum electrolytes right-before and 30 min right-after injecting the patient with his insulin. Potassium dropped by about 16% from its initial level, compared to a drop of only around 4% for calcium and none (0%) for magnesium. Thus, we speculated this insulin-induced sharp drop in serum potassium levels as potentiating the patient's already existing advanced diabetic neuropathy, thereby leading to muscle cramping. However, attempting potassium supplementation for a brief period of time led to a rapid resolution of cramps when they occurred and an overall reduction in their frequency of recurrence. This tilted our diagnosis toward the insulin-induced acute drop in serum potassium levels as the most likely etiology underlying the patient's cramps. Such an observation has been made only once previously within the literature, back in 1992, at the Duke University Medical Center. PMID- 28993758 TI - Experimental Models of Maternal Obesity and Neuroendocrine Programming of Metabolic Disorders in Offspring. AB - Evidence from epidemiological, clinical, and experimental studies have clearly shown that disease risk in later life is increased following a poor early life environment, a process preferentially termed developmental programming. In particular, this work clearly highlights the importance of the nutritional environment during early development with alterations in maternal nutrition, including both under- and overnutrition, increasing the risk for a range of cardiometabolic and neurobehavioral disorders in adult offspring characterized by both adipokine resistance and obesity. Although the mechanistic basis for such developmental programming is not yet fully defined, a common feature derived from experimental animal models is that of alterations in the wiring of the neuroendocrine pathways that control energy balance and appetite regulation during early stages of developmental plasticity. The adipokine leptin has also received significant attention with clear experimental evidence that normal regulation of leptin levels during the early life period is critical for the normal development of tissues and related signaling pathways that are involved in metabolic and cardiovascular homeostasis. There is also increasing evidence that alterations in the epigenome and other underlying mechanisms including an altered gut-brain axis may contribute to lasting cardiometabolic dysfunction in offspring. Ongoing studies that further define the mechanisms between these associations will allow for identification of early risk markers and implementation of strategies around interventions that will have obvious beneficial implications in breaking a programmed transgenerational cycle of metabolic disorders. PMID- 28993760 TI - Monitoring the Secretory Behavior of the Rat Adrenal Medulla by High-Performance Liquid Chromatography-Based Catecholamine Assay from Slice Supernatants. AB - Catecholamine (CA) secretion from the adrenal medullary tissue is a key step of the adaptive response triggered by an organism to cope with stress. Whereas molecular and cellular secretory processes have been extensively studied at the single chromaffin cell level, data available for the whole gland level are much scarcer. We tackled this issue in rat by developing an easy to implement experimental strategy combining the adrenal acute slice supernatant collection with a high-performance liquid chromatography-based epinephrine and norepinephrine (NE) assay. This technique affords a convenient method for measuring basal and stimulated CA release from single acute slices, allowing thus to individually address the secretory function of the left and right glands. Our data point that the two glands are equally competent to secrete epinephrine and NE, exhibiting an equivalent epinephrine:NE ratio, both at rest and in response to a cholinergic stimulation. Nicotine is, however, more efficient than acetylcholine to evoke NE release. A pharmacological challenge with hexamethonium, an alpha3-containing nicotinic acetylcholine receptor antagonist, disclosed that epinephrine- and NE-secreting chromaffin cells distinctly expressed alpha3 nicotinic receptors, with a dominant contribution in NE cells. As such, beyond the novelty of CA assays from acute slice supernatants, our study contributes at refining the secretory behavior of the rat adrenal medullary tissue, and opens new perspectives for monitoring the release of other hormones and transmitters, especially those involved in the stress response. PMID- 28993759 TI - The Four-Way Stop Sign: Viruses, 12-Lipoxygenase, Islets, and Natural Killer Cells in Type 1 Diabetes Progression. AB - Natural killer (NK) cells represent an important effector arm against viral infection, and mounting evidence suggests that viral infection plays a role in the development of type 1 diabetes (T1D) in at least a portion of patients. NK cells recognize their target cells through a delicate balance of inhibitory and stimulatory receptors on their surface. If unbalanced, NK cells have great potential to wreak havoc in the pancreas due to the beta cell expression of the as-yet-defined NKp46 ligand through interactions with the activating NKp46 receptor found on the surface of most NK cells. Blocking interactions between NKp46 and its ligand protects mice from STZ-induced diabetes, but differential expression non-diabetic and diabetic donor samples have not been tested. Additional studies have shown that peripheral blood NK cells from human T1D patients have altered phenotypes that reduce the lytic and functional ability of the NK cells. Investigations of humanT1D pancreas tissues have indicated that the presence of NK cells may be beneficial despite their infrequent detection. In non obese diabetic (NOD) mice, we have noted that NK cells express high levels of the proinflammatory mediator 12/15-lipoxygenase (12/15-LO), and decreased levels of stimulatory receptors. Conversely, NK cells of 12/15-LO deficient NOD mice, which are protected from diabetes development, express significantly higher levels of stimulatory receptors. Furthermore, the human NK92 cell line expresses the ALOX12 protein [human 12-lipoxygenase (12-LO), related to mouse 12/15-LO] via Western blotting. Human 12-LO is upregulated in the pancreas of both T1D and T2D human donors with insulin-containing islets, showing a link between 12-LO expression and diabetes progression. Therefore, our hypothesis is that NK cells in those susceptible to developing T1D are unable to function properly during viral infections of pancreatic beta cells due to increased 12-LO expression and activation, which contributes to increased interferon-gamma production and an imbalance in activating and inhibitory NK cell receptors, and may contribute to downstream autoimmune T cell responses. The work presented here outlines evidence from our lab, as well as published literature, supporting our hypothesis, including novel data. PMID- 28993762 TI - Commentary: Lactobacilli Dominance and Vaginal pH: Why Is the Human Vaginal Microbiome Unique? PMID- 28993761 TI - PCR and Omics Based Techniques to Study the Diversity, Ecology and Biology of Anaerobic Fungi: Insights, Challenges and Opportunities. AB - Anaerobic fungi (phylum Neocallimastigomycota) are common inhabitants of the digestive tract of mammalian herbivores, and in the rumen, can account for up to 20% of the microbial biomass. Anaerobic fungi play a primary role in the degradation of lignocellulosic plant material. They also have a syntrophic interaction with methanogenic archaea, which increases their fiber degradation activity. To date, nine anaerobic fungal genera have been described, with further novel taxonomic groupings known to exist based on culture-independent molecular surveys. However, the true extent of their diversity may be even more extensively underestimated as anaerobic fungi continue being discovered in yet unexplored gut and non-gut environments. Additionally many studies are now known to have used primers that provide incomplete coverage of the Neocallimastigomycota. For ecological studies the internal transcribed spacer 1 region (ITS1) has been the taxonomic marker of choice, but due to various limitations the large subunit rRNA (LSU) is now being increasingly used. How the continued expansion of our knowledge regarding anaerobic fungal diversity will impact on our understanding of their biology and ecological role remains unclear; particularly as it is becoming apparent that anaerobic fungi display niche differentiation. As a consequence, there is a need to move beyond the broad generalization of anaerobic fungi as fiber-degraders, and explore the fundamental differences that underpin their ability to exist in distinct ecological niches. Application of genomics, transcriptomics, proteomics and metabolomics to their study in pure/mixed cultures and environmental samples will be invaluable in this process. To date the genomes and transcriptomes of several characterized anaerobic fungal isolates have been successfully generated. In contrast, the application of proteomics and metabolomics to anaerobic fungal analysis is still in its infancy. A central problem for all analyses, however, is the limited functional annotation of anaerobic fungal sequence data. There is therefore an urgent need to expand information held within publicly available reference databases. Once this challenge is overcome, along with improved sample collection and extraction, the application of these techniques will be key in furthering our understanding of the ecological role and impact of anaerobic fungi in the wide range of environments they inhabit. PMID- 28993764 TI - Legacy Effects on the Recovery of Soil Bacterial Communities from Extreme Temperature Perturbation. AB - The type and frequency of disturbances experienced by soil microbiomes is expected to increase given predicted global climate change scenarios and intensified anthropogenic pressures on ecosystems. While the direct effect of multiple disturbances to soil microbes has been explored in terms of function, their effect on the recovery of microbial community composition remains unclear. Here, we used soil microcosm experiments and multiple model disturbances to explore their short-term effect on the recovery of soil microbiota after identical or novel stresses. Soil microcosms were exposed to a heat shock to create an initial effect. Upon initial community recovery (25 days after stress), they were subjected to a second stress, either a heat or a cold shock, and they were monitored for additional 25 days. To carefully verify the bacterial response to the disturbances, we monitored changes in community composition throughout the experiment using 16S rRNA gene transcript amplicon sequencing. The application of a heat shock to soils with or without the initial heat shock resulted in similar successional dynamics, but these dynamics were faster in soils with a prior heat shock. The application of a cold shock had negligible effects on previously undisturbed soils but, in combination with an initial heat shock, caused the largest shift in the community composition. Our findings show that compounded perturbation affects bacterial community recovery by altering community structure and thus, the community's response during succession. By altering dominance patterns, disturbance legacy affects the microbiome's ability to recover from further perturbation within the 25 days studied. Our results highlight the need to consider the soil's disturbance history in the development of soil management practices in order to maintain the system's resilience. PMID- 28993763 TI - Sixty Years (1957-2017) of Research on Toxoplasmosis in China-An Overview. AB - Toxoplasma gondii is a ubiquitous zoonotic pathogen belonging to apicomplexan parasites. Infection in humans and animals may cause abortion and other severe symptoms under certain circumstances, leading to great economical losses and public health problems. T. gondii was first discovered in China in 1955 and the corresponding work was published in 1957. Since then, a lot of work has been done on this parasite and the diseases it causes. This review summarizes the major progress made by Chinese scientists over the last 60 years, and gives our perspectives on what should be done in the near future. A wide variety of diagnostic approaches were designed, including the ones to detect T. gondii specific antibodies in host sera, and T. gondii specific antigens or DNA in tissue and environmental samples. Further work will be needed to translate some of the laboratory assays into reliable products for clinic uses. Epidemiological studies were extensively done in China and the sero-prevalence in humans increased over the years, but is still below the world average, likely due to the unique eating and cooking habits. Infection rates were shown to be fairly high in meat producing animals such as, pigs, sheep, and chickens, as well as in the definitive host cats. Numerous subunit vaccines in the form of recombinant proteins or DNA vaccines were developed, but none of them is satisfactory in the current form. Live attenuated parasites using genetically modified strains may be a better option for vaccine design. The strains isolated from China are dominated by the ToxoDB #9 genotype, but it likely contains multiple subtypes since different ToxoDB #9 strains exhibited phenotypic differences. Further studies are needed to understand the general biology, as well as the unique features of strains prevalent in China. PMID- 28993765 TI - Prolonged Excretion of Poliovirus among Individuals with Primary Immunodeficiency Disorder: An Analysis of the World Health Organization Registry. AB - Individuals with primary immunodeficiency disorder may excrete poliovirus for extended periods and will constitute the only remaining reservoir of virus after eradication and withdrawal of oral poliovirus vaccine. Here, we analyzed the epidemiology of prolonged and chronic immunodeficiency-related vaccine-derived poliovirus cases in a registry maintained by the World Health Organization, to identify risk factors and determine the length of excretion. Between 1962 and 2016, there were 101 cases, with 94/101 (93%) prolonged excretors and 7/101 (7%) chronic excretors. We documented an increase in incidence in recent decades, with a shift toward middle-income countries, and a predominance of poliovirus type 2 in 73/101 (72%) cases. The median length of excretion was 1.3 years (95% confidence interval: 1.0, 1.4) and 90% of individuals stopped excreting after 3.7 years. Common variable immunodeficiency syndrome and residence in high-income countries were risk factors for long-term excretion. The changing epidemiology of cases, manifested by the greater incidence in recent decades and a shift to from high- to middle-income countries, highlights the expanding risk of poliovirus transmission after oral poliovirus vaccine cessation. To better quantify and reduce this risk, more sensitive surveillance and effective antiviral therapies are needed. PMID- 28993766 TI - Therapeutic Potential of Shark Anti-ICOSL VNAR Domains is Exemplified in a Murine Model of Autoimmune Non-Infectious Uveitis. AB - Induced costimulatory ligand (ICOSL) plays an important role in the activation of T cells through its interaction with the inducible costimulator, ICOS. Suppression of full T cell activation can be achieved by blocking this interaction and has been shown to be an effective means of ameliorating disease in models of autoimmunity and inflammation. In this study, we demonstrated the ability of a novel class of anti-ICOSL antigen-binding single domains derived from sharks (VNARs) to effectively reduce inflammation in a murine model of non infectious uveitis. In initial selections, specific VNARs that recognized human ICOSL were isolated from an immunized nurse shark phage display library and lead domains were identified following their performance in a series of antigen selectivity and in vitro bioassay screens. High potency in cell-based blocking assays suggested their potential as novel binders suitable for further therapeutic development. To test this hypothesis, surrogate anti-mouse ICOSL VNAR domains were isolated from the same phage display library and the lead VNAR clone selected via screening in binding and ICOS/ICOSL blocking experiments. The VNAR domain with the highest potency in cell-based blocking of ICOS/ICOSL interaction was fused to the Fc portion of human IgG1 and was tested in vivo in a mouse model of interphotoreceptor retinoid-binding protein-induced uveitis. The anti-mICOSL VNAR Fc, injected systemically, resulted in a marked reduction of inflammation in treated mice when compared with untreated control animals. This approach inhibited disease progression to an equivalent extent to that seen for the positive corticosteroid control, cyclosporin A, reducing both clinical and histopathological scores. These results represent the first demonstration of efficacy of a VNAR binding domain in a relevant clinical model of disease and highlight the potential of VNARs for the treatment of auto-inflammatory conditions. PMID- 28993768 TI - CD30 Is Dispensable for T-Cell Responses to Influenza Virus and Lymphocytic Choriomeningitis Virus Clone 13 but Contributes to Age-Associated T-Cell Expansion in Mice. AB - CD30 is a tumor necrosis factor receptor (TNFR) family member whose expression is associated with Hodgkin's disease, anaplastic large cell lymphomas, and other T and B lymphoproliferative disorders in humans. A limited number of studies have assessed the physiological role of CD30/CD30 ligand interactions in control of infection in mice. Here, we assess the role of CD30 in T-cell immunity to acute influenza and chronic lymphocytic choriomeningitis virus (LCMV) clone 13 infection, two viral infections in which other members of the TNFR superfamily are important for T-cell responses. We show that CD30 is expressed on activated but not resting CD4 and CD8 T cells in vitro, as well as on regulatory T cells and marginally on T helper 1 cells in vivo during influenza infection. Despite this, CD4 and CD8 T-cell expansion in response to influenza virus was comparable in CD30+/+ and CD30-/- littermates, with no discernable role for the pathway in the outcome of influenza infection. Similarly, during persistent infection with LCMV clone 13, CD30 plays no obvious role in CD4 or CD8 T-cell responses, the level of T-cell exhaustion or viral control. In contrast, in the steady state, we observed increased numbers of total CD4 and CD8 T cells as well as increased numbers of regulatory T cells in unimmunized older (~8 months) CD30+/+ but not in CD30-/- age-matched littermates. Naive T-cell numbers were unchanged in the aged CD30+/+ mice compared to their CD30-/- littermate controls, rather the T-cell expansions were explained by an increase in CD4+ and CD8+ CD44mid-hiCD62L- effector memory cells, with a similar trend in the central memory T-cell compartment. In contrast, CD30 did not impact the numbers of T cells in young mice. These data suggest a role for CD30 in the homeostatic regulation of T cells during aging, contributing to memory T-cell expansions, which may have relevance for CD30 expression in human T-cell lymphoproliferative diseases. PMID- 28993767 TI - Genomic Programming of Human Neonatal Dendritic Cells in Congenital Systemic and In Vitro Cytomegalovirus Infection Reveal Plastic and Robust Immune Pathway Biology Responses. AB - Neonates and especially premature infants are highly susceptible to infection but still can have a remarkable resilience that is poorly understood. The view that neonates have an incomplete or deficient immune system is changing. Human neonatal studies are challenging, and elucidating host protective responses and underlying cognate pathway biology, in the context of viral infection in early life, remains to be fully explored. In both resource rich and poor settings, human cytomegalovirus (HCMV) is the most common cause of congenital infection. By using unbiased systems analyses of transcriptomic resources for HCMV neonatal infection, we find the systemic response of a preterm congenital HCMV infection, involves a focused IFN regulatory response associated with dendritic cells. Further analysis of transcriptional-programming of neonatal dendritic cells in response to HCMV infection in culture revealed an early dominant IFN-chemokine regulatory subnetworks, and at later times the plasticity of pathways implicated in cell-cycle control and lipid metabolism. Further, we identify previously unknown suppressed networks associated with infection, including a select group of GPCRs. Functional siRNA viral growth screen targeting 516-GPCRs and subsequent validation identified novel GPCR-dependent antiviral (ADORA1) and proviral (GPR146, RGS16, PTAFR, SCTR, GPR84, GPR85, NMUR2, FZ10, RDS, CCL17, and SORT1) roles. By contrast a gene family cluster of protocadherins is significantly differentially induced in neonatal cells, suggestive of possible immunomodulatory roles. Unexpectedly, programming responses of adult and neonatal dendritic cells, upon HCMV infection, demonstrated comparable quantitative and qualitative responses showing that functionally, neonatal dendritic cell are not overly compromised. However, a delay in responses of neonatal cells for IFN subnetworks in comparison with adult-derived cells are notable, suggestive of subtle plasticity differences. These findings support a set-point control mechanism rather than immaturity for explaining not only neonatal susceptibility but also resilience to infection. In summary, our findings show that neonatal HCMV infection leads to a highly plastic and functional robust programming of dendritic cells in vivo and in vitro. In comparison with adults, a minimal number of subtle quantitative and temporal differences may contribute to variability in host susceptibility and resilience, in a context dependent manner. PMID- 28993769 TI - Phosphoproteomics Reveals Regulatory T Cell-Mediated DEF6 Dephosphorylation That Affects Cytokine Expression in Human Conventional T Cells. AB - Regulatory T cells (Tregs) control key events of immune tolerance, primarily by suppression of effector T cells. We previously revealed that Tregs rapidly suppress T cell receptor (TCR)-induced calcium store depletion in conventional CD4+CD25- T cells (Tcons) independently of IP3 levels, consequently inhibiting NFAT signaling and effector cytokine expression. Here, we study Treg suppression mechanisms through unbiased phosphoproteomics of primary human Tcons upon TCR stimulation and Treg-mediated suppression, respectively. Tregs induced a state of overall decreased phosphorylation as opposed to TCR stimulation. We discovered novel phosphosites (T595_S597) in the DEF6 (SLAT) protein that were phosphorylated upon TCR stimulation and conversely dephosphorylated upon coculture with Tregs. Mutation of these DEF6 phosphosites abrogated interaction of DEF6 with the IP3 receptor and affected NFAT activation and cytokine transcription in primary Tcons. This novel mechanism and phosphoproteomics data resource may aid in modifying sensitivity of Tcons to Treg-mediated suppression in autoimmune disease or cancer. PMID- 28993770 TI - Adjuvant-Mediated Epitope Specificity and Enhanced Neutralizing Activity of Antibodies Targeting Dengue Virus Envelope Protein. AB - The heat-labile toxins (LT) produced by enterotoxigenic Escherichia coli display adjuvant effects to coadministered antigens, leading to enhanced production of serum antibodies. Despite extensive knowledge of the adjuvant properties of LT derivatives, including in vitro-generated non-toxic mutant forms, little is known about the capacity of these adjuvants to modulate the epitope specificity of antibodies directed against antigens. This study characterizes the role of LT and its non-toxic B subunit (LTB) in the modulation of antibody responses to a coadministered antigen, the dengue virus (DENV) envelope glycoprotein domain III (EDIII), which binds to surface receptors and mediates virus entry into host cells. In contrast to non-adjuvanted or alum-adjuvanted formulations, antibodies induced in mice immunized with LT or LTB showed enhanced virus-neutralization effects that were not ascribed to a subclass shift or antigen affinity. Nonetheless, immunosignature analyses revealed that purified LT-adjuvanted EDIII specific antibodies display distinct epitope-binding patterns with regard to antibodies raised in mice immunized with EDIII or the alum-adjuvanted vaccine. Notably, the analyses led to the identification of a specific EDIII epitope located in the EF to FG loop, which is involved in the entry of DENV into eukaryotic cells. The present results demonstrate that LT and LTB modulate the epitope specificity of antibodies generated after immunization with coadministered antigens that, in the case of EDIII, was associated with the induction of neutralizing antibody responses. These results open perspectives for the more rational development of vaccines with enhanced protective effects against DENV infections. PMID- 28993771 TI - Tumor-Derived Microvesicles Modulate Antigen Cross-Processing via Reactive Oxygen Species-Mediated Alkalinization of Phagosomal Compartment in Dendritic Cells. AB - Dendritic cells (DCs) are the only antigen-presenting cells able to prime naive T cells and cross-prime antigen-specific CD8+ T cells. Their functionality is a requirement for the induction and maintenance of long-lasting cancer immunity. Albeit intensively investigated, the in vivo mechanisms underlying efficient antigen cross-processing and presentation are not fully understood. Several pieces of evidence indicate that antigen transfer to DCs mediated by microvesicles (MVs) enhances antigen immunogenicity. This mechanism is also relevant for cross-presentation of those tumor-associated glycoproteins such as MUC1 that are blocked in HLA class II compartment when internalized by DCs as soluble molecules. Here, we present pieces of evidence that the internalization of tumor-derived MVs modulates antigen-processing machinery of DCs. Employing MVs derived from ovarian cancer ascites fluid and established tumor cell lines, we show that MV uptake modifies DC phagosomal microenvironment, triggering reactive oxygen species (ROS) accumulation and early alkalinization. Indeed, tumor MVs carry radical species and the MV uptake by DCs counteracts the chemically mediated acidification of the phagosomal compartment. Further pieces of evidence suggest that efficacious antigen cross-priming of the MUC1 antigen carried by the tumor MVs results from the early signaling induced by MV internalization and the function of the antigen-processing machinery of DCs. These results strongly support the hypothesis that tumor-derived MVs impact antigen immunogenicity by tuning the antigen-processing machinery of DCs, besides being carrier of tumor antigens. Furthermore, these findings have important implications for the exploitation of MVs as antigenic cell-free immunogen for DC-based therapeutic strategies. PMID- 28993772 TI - Rescuing Self: Transient Isolation and Autologous Transplantation of Bone Marrow Mitigates Radiation-Induced Hematopoietic Syndrome and Mortality in Mice. AB - The inflamed bone marrow niche shortly after total body irradiation (TBI) is known to contribute to loss of hematopoietic stem cells in terms of their number and function. In this study, autologous bone marrow transfer (AL-BMT) was evaluated as a strategy for mitigating hematopoietic form of the acute radiation syndrome by timing the collection phase (2 h after irradiation) and reinfusion (24 h after irradiation) using mice as a model system. Collection of bone marrow (BM) cells (0.5 * 106 total marrow cells) 2 h after lethal TBI rescued different subclasses of hematopoietic stem and progenitor cells (HSPCs) from the detrimental inflammatory and damaging milieu in vivo. Cryopreservation of collected graft and its reinfusion 24 h after TBI significantly rescued mice from lethal effects of irradiation (65% survival against 0% in TBI group on day 30th) and hematopoietic depression. Transient hypometabolic state (HMS) induced 2 h after TBI effectively preserved the functional status of HSPCs and improved hematopoietic recovery even when BM was collected 8 h after TBI. Homing studies suggested that AL-BMT yielded similar percentages for different subsets of HSPCs when compared to syngeneic bone marrow transfer. The results suggest that the timing of collection, and reinfusion of graft is crucial for the success of AL BMT. PMID- 28993773 TI - Targeting Malignant Brain Tumors with Antibodies. AB - Antibodies have been shown to be a potent therapeutic tool. However, their use for targeting brain diseases, including neurodegenerative diseases and brain cancers, has been limited, particularly because the blood-brain barrier (BBB) makes brain tissue hard to access by conventional antibody-targeting strategies. In this review, we summarize new antibody therapeutic approaches to target brain tumors, especially malignant gliomas, as well as their potential drawbacks. Many different brain delivery platforms for antibodies have been studied such as liposomes, nanoparticle-based systems, cell-penetrating peptides (CPPs), and cell based approaches. We have already shown the successful delivery of single-chain fragment variable (scFv) with CPP as a linker between two variable domains in the brain. Antibodies normally face poor penetration through the BBB, with some variants sufficiently passing the barrier on their own. A "Trojan horse" method allows passage of biomolecules, such as antibodies, through the BBB by receptor mediated transcytosis (RMT). Such examples of therapeutic antibodies are the bispecific antibodies where one binding specificity recognizes and binds a BBB receptor, enabling RMT and where a second binding specificity recognizes an antigen as a therapeutic target. On the other hand, cell-based systems such as stem cells (SCs) are a promising delivery system because of their tumor tropism and ability to cross the BBB. Genetically engineered SCs can be used in gene therapy, where they express anti-tumor drugs, including antibodies. Different types and sources of SCs have been studied for the delivery of therapeutics to the brain; both mesenchymal stem cells (MSCs) and neural stem cells (NSCs) show great potential. Following the success in treatment of leukemias and lymphomas, the adoptive T-cell therapies, especially the chimeric antigen receptor-T cells (CAR-Ts), are making their way into glioma treatment as another type of cell based therapy using the antibody to bind to the specific target(s). Finally, the current clinical trials are reviewed, showing the most recent progress of attractive approaches to deliver therapeutic antibodies across the BBB aiming at the specific antigen. PMID- 28993775 TI - IL-27-Induced Type 1 Regulatory T-Cells Produce Oxysterols that Constrain IL-10 Production. AB - The behaviors of lymphocytes, including CD4+ T helper cells, are controlled on many levels by internal metabolic properties. Lipid metabolites have recently been ascribed a novel function as immune response modulators and perturbation of steroids pathways modulates inflammation and potentially promotes a variety of diseases. However, the impact of lipid metabolism on autoimmune disease development and lymphocyte biology is still largely unraveled. In this line, oxysterols, oxidized forms of cholesterol, have pleiotropic roles on the immune response aside from their involvements in lipid metabolism. The oxysterols 25 hydroxycholesterol (25-OHC) and 7alpha,25-dihydroxycholesterol (7alpha,25-OHC) regulate antiviral immunity and immune cell chemotaxis. However, their physiological effects on adaptive immune response in particular on various subset CD4+ T lymphocytes are largely unknown. Here, we assessed oxysterol levels in subset of CD4+ T cells and demonstrated that 25-OHC and transcript levels of its synthesizing enzyme, cholesterol 25-hydroxylase, were specifically increased in IL-27-induced type 1 regulatory T (TR1) cells. We further showed that 25-OHC acts as a negative regulator of TR1 cells in particular of IL-10 secretion via liver X receptor signaling. Not only do these findings unravel molecular mechanisms accounting for IL-27 signaling but also they highlight oxysterols as pro inflammatory mediators that dampens regulatory T cell responses and thus unleash a pro-inflammatory response. PMID- 28993776 TI - Human Cytomegalovirus Delays Neutrophil Apoptosis and Stimulates the Release of a Prosurvival Secretome. AB - Human cytomegalovirus (HCMV) is a major cause of viral disease in the young and the immune-suppressed. At sites of infection, HCMV recruits the neutrophil, a cell with a key role in orchestrating the initial immune response. Herein, we report a profound survival response in human neutrophils exposed to the clinical HCMV isolate Merlin, but not evident with the attenuated strain AD169, through suppression of apoptosis. The initial survival event, which is independent of viral gene expression and involves activation of the ERK/MAPK and NF-kappaB pathways, is augmented by HCMV-stimulated release of a secretory cytokine profile that further prolongs neutrophil lifespan. As aberrant neutrophil survival contributes to tissue damage, we predict that this may be relevant to the immune pathology of HCMV, and the presence of this effect in clinical HCMV strains and its absence in attenuated strains implies a beneficial effect to the virus in pathogenesis and/or dissemination. In addition, we show that HCMV-exposed neutrophils release factors that enhance monocyte recruitment and drive monocyte differentiation to a HCMV-permissive phenotype in an IL-6-dependent manner, thus providing an ideal vehicle for viral dissemination. This study increases understanding of HCMV-neutrophil interactions, highlighting the potential role of neutrophil recruitment as a virulence mechanism to promote HCMV pathology in the host and influence the dissemination of HCMV infection. Targeting these mechanisms may lead to new antiviral strategies aimed at limiting host damage and inhibiting viral spread. PMID- 28993777 TI - The Procoagulant Activity of Apoptotic Cells Is Mediated by Interaction with Factor XII. AB - Apoptotic cells, by externalizing phosphatidylserine (PS) as a hallmark feature, are procoagulant. However, the mechanism by which apoptotic cells activate coagulation system remains unknown. Intrinsic coagulation pathway is initiated by coagulation factor XII (FXII) of contact activation system. The purpose of this study was to determine whether FXII is involved in procoagulant activity of apoptotic cells. Using western blotting and chromogenic substrate assay, we found that incubation with apoptotic cells, but not with viable cells, resulted in rapid cleavage and activation of FXII in the presence of prekallikrein and high molecular weight kininogen (HK), other two components of contact activation system. As detected by flow cytometry, FXII bound to apoptotic cells in a concentration-dependent manner, which was inhibited by annexin V and PS liposome. Direct association of FXII with PS was confirmed in a surface plasmon resonance assay. Clotting time of FXII-deficient plasma induced by apoptotic cells was significantly prolonged, which was fully reversed by replenishment with FXII. Corn trypsin inhibitor, a FXII inhibitor, completely prevented apoptotic cells induced intrinsic tenase complex formation. Consistently, apoptotic cells significantly increased thrombin production in normal plasma, which was not affected by an inhibitory anti-tissue factor antibody. However, blocking of PS by annexin V, inhibition of FXII, or the deficiency of FXII suppressed apoptotic cells-induced thrombin generation. Addition of purified FXII to FXII-deficient plasma recovered thrombin generation to the normal plasma level. In conclusion, FXII binds to apoptotic cells via PS and becomes activated, thereby constituting a novel mechanism mediating the procoagulant activity of apoptotic cells. PMID- 28993774 TI - The Clinical Application of MicroRNAs in Infectious Disease. AB - MicroRNAs (miRNAs) are short single-stranded non-coding RNA sequences that posttranscriptionally regulate up to 60% of protein encoding genes. Evidence is emerging that miRNAs are key mediators of the host response to infection, predominantly by regulating proteins involved in innate and adaptive immune pathways. miRNAs can govern the cellular tropism of some viruses, are implicated in the resistance of some individuals to infections like HIV, and are associated with impaired vaccine response in older people. Not surprisingly, pathogens have evolved ways to undermine the effects of miRNAs on immunity. Recognition of this has led to new experimental treatments, RG-101 and Miravirsen-hepatitis C treatments which target host miRNA. miRNAs are being investigated as novel infection biomarkers, and they are being used to design attenuated vaccines, e.g., against Dengue virus. This comprehensive review synthesizes current knowledge of miRNA in host response to infection with emphasis on potential clinical applications, along with an evaluation of the challenges still to be overcome. PMID- 28993778 TI - Potential Role of Vdelta2+ gammadelta T Cells in Regulation of Immune Activation in Primary HIV Infection. AB - Although conventional regulatory T cells (Tregs) are sufficient in controlling low residual T-cell activation in ART-treated patients, they are not efficient in controlling exaggerated immune activation associated with high levels of HIV replication in primary HIV infection (PHI). Our previous data suggested that double negative (DN) T cells including mainly gammadelta DN T cells play a role in the control of immune activation in PHI. Since gammadelta T cells are capable of exerting regulatory functions, we investigated their implication as Tregs in PHI as well as chronic HIV infection (CHI). In a cross-sectional study of 58 HIV infected patients, in the primary and the chronic phase either ART-treated or untreated (UT), we analyzed phenotype and cytokine production of gammadelta T cells using flow cytometry. Cytokine production was assessed following in vitro stimulation with isopentenyl pyrophosphate or plate-bound anti-CD3/anti-CD28 monoclonal antibodies. We found that the proportion of gammadelta T cells negatively correlated with CD8 T-cell activation in PHI patients. Furthermore, we found that in these patients, the Vdelta2 receptor bearing (Vdelta2+) gammadelta T cells were strongly activated, exhibited low terminal differentiation, and produced the anti-inflammatory cytokine, TGF-beta. In contrast, in UT-CHI, we observed a remarkable expansion of gammadelta T cells, where the Vdelta2+ gammadelta T cells comprised of an elevated proportion of terminally differentiated cells producing high levels of IFN-gamma but very low levels of TGF-beta. We also found that this loss of regulatory feature of gammadelta T cells in CHI was a lasting impairment as we did not find recovery of TGF-beta production even in ART-CHI patients successfully treated for more than 5 years. Our data therefore suggest that during the primary HIV infection, Vdelta2+ gammadelta T cells may act as Tregs controlling immune activation through production of TGF-beta. However, in CHI, gammadelta T cells transform from an anti-inflammatory into pro-inflammatory cytokine profile and participate in sustenance of immune activation. PMID- 28993782 TI - Root Traits, Nodulation and Root Distribution in Soil for Five Wild Lentil Species and Lens culinaris (Medik.) Grown under Well-Watered Conditions. AB - The efficient use of resources such as water and nutrients by plants is increasingly important as the world population food demand continues to grow. With the increased production of lentil in the temperate zones of North America, improvement in yield needs to be maintained. The use of wild lentil genotypes as sources of genetic diversity for introgression into cultivated lentil is an important breeding strategy, but little is known about their root systems. We evaluated the root systems of five wild lentil species and Lens culinaris under fully watered conditions. Plants were grown in 60 cm tubes containing equal volumes of soil collected from the reconstructed A, B, and C horizons. Significant differences were observed for root traits and fine root distribution between and within species and the proportion of root biomass partitioned into each soil layer was unique for each genotype. We also observed variability in nodule number and nodule shape within and between genotypes. Some genotypes more efficiently used water for either biomass or seed production. The allocation of resources to seed production also varied between genotypes. These observations could have impact on the design of future lentil breeding in the context of strategies for managing changes in rainfall amount and distribution for lentil production ecosystems. PMID- 28993779 TI - Natural Killer Cell Response to Chemotherapy-Stressed Cancer Cells: Role in Tumor Immunosurveillance. AB - Natural killer (NK) cells are innate cytotoxic lymphoid cells that actively prevent neoplastic development, growth, and metastatic dissemination in a process called cancer immunosurveillance. An equilibrium between immune control and tumor growth is maintained as long as cancer cells evade immunosurveillance. Therapies designed to kill cancer cells and to simultaneously sustain host antitumor immunity are an appealing strategy to control tumor growth. Several chemotherapeutic agents, depending on which drugs and doses are used, give rise to DNA damage and cancer cell death by means of apoptosis, immunogenic cell death, or other forms of non-apoptotic death (i.e., mitotic catastrophe, senescence, and autophagy). However, it is becoming increasingly clear that they can trigger additional stress responses. Indeed, relevant immunostimulating effects of different therapeutic programs include also the activation of pathways able to promote their recognition by immune effector cells. Among stress inducible immunostimulating proteins, changes in the expression levels of NK cell activating and inhibitory ligands, as well as of death receptors on tumor cells, play a critical role in their detection and elimination by innate immune effectors, including NK cells. Here, we will review recent advances in chemotherapy-mediated cellular stress pathways able to stimulate NK cell effector functions. In particular, we will address how these cytotoxic lymphocytes sense and respond to different types of drug-induced stresses contributing to anticancer activity. PMID- 28993781 TI - Natural Killer T Cell-Targeted Immunotherapy Mediating Long-term Memory Responses and Strong Antitumor Activity. AB - Current tumor therapies, including immunotherapies, focus on passive eradication or at least reduction of the tumor mass. However, cancer patients quite often suffer from tumor relapse or metastasis after such treatments. To overcome these problems, we have developed a natural killer T (NKT) cell-targeted immunotherapy focusing on active engagement of the patient's immune system, but not directly targeting the tumor cells themselves. NKT cells express an invariant antigen receptor alpha chain encoded by Trav11 (Valpha14)-Traj18 (Jalpha18) gene segments in mice and TRAV10 (Valpha24)-TRAJ18 (Jalpha18) in humans and recognize glycolipid ligand in conjunction with a monomorphic CD1d molecule. The NKT cells play a pivotal role in the orchestration of antitumor immune responses by mediating adjuvant effects that activate various antitumor effector cells of both innate and adaptive immune systems and also aid in establishing a long-term memory response. Here, we established NKT cell-targeted therapy using a newly discovered NKT cell glycolipid ligand, RK, which has a stronger capacity to stimulate both human and mouse NKT cells compared to previous NKT cell ligand. Moreover, RK mediates strong adjuvant effects in activating various effector cell types and establishes long-term memory responses, resulting in the continuous attack on the tumor that confers long-lasting and potent antitumor effects. Since the NKT cell ligand presented by the monomorphic CD1d can be used for all humans irrespective of HLA types, and also because NKT cell-targeted therapy does not directly target tumor cells, this therapy can potentially be applied to all cancer patients and any tumor types. PMID- 28993783 TI - Genetic Variability of 27 Traits in a Core Collection of Flax (Linum usitatissimum L.). AB - Assessment of genetic variability of plant core germplasm is needed for efficient germplasm utilization in breeding improvement. A total of 391 accessions of a flax core collection, which preserves the variation present in the world collection of 3,378 accessions maintained by Plant Gene Resources of Canada (PGRC) and represents a broad range of geographical origins, different improvement statuses and two morphotypes, was evaluated in field trials in up to 8 year-location environments for 10 agronomic, eight seed quality, six fiber and three disease resistance traits. The large phenotypic variation in this subset was explained by morphotypes (22%), geographical origins (11%), and other variance components (67%). Both divergence and similarity between two basic morphotypes, namely oil or linseed and fiber types, were observed, whereby linseed accessions had greater thousand seed weight, seeds m-2, oil content, branching capability and resistance to powdery mildew while fiber accessions had greater straw weight, plant height, protein content and resistance to pasmo and fusarium wilt diseases, but they had similar performance in many traits and some of them shared common characteristics of fiber and linseed types. Weak geographical patterns within either fiber or linseed accessions were confirmed, but specific trait performance was identified in East Asia for fiber type, and South Asia and North America for linseed type. Relatively high broad-sense heritability was obtained for seed quality traits, followed by agronomic traits and resistance to powdery mildew and fusarium wilt. Diverse phenotypic and genetic variability in the flax core collection constitutes a useful resource for breeding. PMID- 28993780 TI - Spontaneous Secretion of the Citrullination Enzyme PAD2 and Cell Surface Exposure of PAD4 by Neutrophils. AB - Autoantibodies directed against citrullinated epitopes of proteins are highly diagnostic of rheumatoid arthritis (RA), and elevated levels of protein citrullination can be found in the joints of patients with RA. Calcium-dependent peptidyl-arginine deiminases (PAD) are the enzymes responsible for citrullination. PAD2 and PAD4 are enriched in neutrophils and likely drive citrullination under inflammatory conditions. PADs may be released during NETosis or cell death, but the mechanisms responsible for PAD activity under physiological conditions have not been fully elucidated. To understand how PADs citrullinate extracellular proteins, we investigated the cellular localization and activity of PAD2 and PAD4, and we report that viable neutrophils from healthy donors have active PAD4 exposed on their surface and spontaneously secrete PAD2. Neutrophil activation by some stimulatory agents increased the levels of immunoreactive PAD4 on the cell surface, and some stimuli reduced PAD2 secretion. Our data indicate that live neutrophils have the inherent capacity to express active extracellular PADs. These novel pathways are distinguished from intracellular PAD activation during NETosis and calcium influx-mediated hypercitrullination. Our study implies that extracellular PADs may have a physiological role under non-pathogenic conditions as well as a pathological role in RA. PMID- 28993785 TI - Vector Transmission Alone Fails to Explain the Potato Yellow Vein Virus Epidemic among Potato Crops in Colombia. AB - The potato yellow vein disease, caused by the potato yellow vein virus (PYVV), is a limiting potato disease in northern South America. The virus can be transmitted either by the greenhouse whitefly (GWF), Trialeurodes vaporariorum (Westwood) (Hemiptera: Aleyrodidae), or through vegetative propagules, such as infected tubers. Recently, GWF populations have been spotlighted as one of the main drivers of PYVV re-emergence, and consequently, PYVV management has been predominantly directed toward vector control, which is heavily based on insecticide use. However, the drivers of the PYVV outbreaks as well as the contribution of GWF populations on the spread of PYVV among potato crops are still not completely understood. This study aims to assess the role of the GWF as a driver of the PYVV epidemic in the potato-producing areas in Colombia, one of the countries more severely affected by the PYVV epidemic, and whose geography allows the study of the spatial association between the vector and the disease epidemic across a wide altitude range. The geographical clusters where the PYVV epidemic is concentrated, as well as those of farms affected by the GWF were identified using a novel spatial epidemiology approach. The influence of altitude range on the association between PYVV and T. vaporarioum was also assessed. We found a relatively poor spatial association between PYVV epidemic and the presence of the GWF, especially at altitudes above 3,000 m above mean sea level. Furthermore, GWF populations could only explain a small fraction of the extent of the PYVV epidemic in Colombia. Movement of infected seed tubers might be the main mechanism of dispersion, and could be a key driver for the PYVV infection among potato crops. Agricultural policies focused on improving quality of seed tubers and their appropriate distribution could be the most efficient control intervention against PYVV dispersion. PMID- 28993784 TI - The Intergenic Interplay between Aldose 1-Epimerase-Like Protein and Pectin Methylesterase in Abiotic and Biotic Stress Control. AB - The mechanical damage that often precedes the penetration of a leaf by a pathogen promotes the activation of pectin methylesterase (PME); the activation of PME leads to the emission of methanol, resulting in a "priming" effect on intact leaves, which is accompanied by an increased sensitivity to Tobacco mosaic virus (TMV) and resistance to bacteria. In this study, we revealed that mRNA levels of the methanol-inducible gene encoding Nicotiana benthamiana aldose 1-epimerase like protein (NbAELP) in the leaves of intact plants are very low compared with roots. However, stress and pathogen attack increased the accumulation of the NbAELP mRNA in the leaves. Using transiently transformed plants, we obtained data to support the mechanism underlying AELP/PME-related negative feedback The insertion of the NbAELP promoter sequence (proNbAELP) into the N. benthamiana genome resulted in the co-suppression of the natural NbAELP gene expression, accompanied by a reduction in the NbAELP mRNA content and increased PME synthesis. Knockdown of NbAELP resulted in high activity of PME in the cell wall and a decrease in the leaf glucose level, creating unfavorable conditions for Agrobacterium tumefaciens reproduction in injected leaves. Our results showed that NbAELP is capable of binding the TMV movement protein (MPTMV) in vitro and is likely to affect the cellular nucleocytoplasmic transport, which may explain the sensitivity of NbAELP knockdown plants to TMV. Although NbAELP was primarily detected in the cell wall, the influence of this protein on cellular PME mRNA levels might be associated with reduced transcriptional activity of the PME gene in the nucleus. To confirm this hypothesis, we isolated the N. tabacum PME gene promoter (proNtPME) and showed the inhibition of proNtPME-directed GFP and GUS expression in leaves when co-agroinjected with the NbAELP-encoding plasmid. We hypothesized that plant wounding and/or pathogen attack lead to PME activation and increased methanol emission, followed by increased NbAELP expression, which results in reversion of PME mRNA level and methanol emission to levels found in the intact plant. PMID- 28993786 TI - An NAM Domain Gene, GhNAC79, Improves Resistance to Drought Stress in Upland Cotton. AB - Plant-specific NAC proteins comprise one of the largest transcription factor families in plants and play important roles in plant development and the stress response. Gossypium hirsutum L. is a major source of fiber, but its growth and productivity are limited by many biotic and abiotic stresses. In this study, the NAC domain gene GhNAC79 was functionally characterized in detail, and according to information about the cotton genome sequences, it was located on scaffold42.1, containing three exons and two introns. Promoter analysis indicated that the GhNAC79 promoter contained both basic and stress-related elements, and it was especially expressed in the cotyledon of Arabidopsis. A transactivation assay in yeast demonstrated that GhNAC79 was a transcription activator, and its activation domain was located at its C-terminus. The results of qRT-PCR proved that GhNAC79 was preferentially expressed at later stages of cotyledon and fiber development, and it showed high sensitivity to ethylene and meJA treatments. Overexpression of GhNAC79 resulted in an early flowering phenotype in Arabidopsis, and it also improved drought tolerance in both Arabidopsis and cotton. Furthermore, VIGS induced silencing of GhNAC79 in cotton led to a drought-sensitive phenotype. In summary, GhNAC79 positively regulates drought stress, and it also responds to ethylene and meJA treatments, making it a candidate gene for stress studies in cotton. PMID- 28993787 TI - Fitness of ALS-Inhibitors Herbicide Resistant Population of Loose Silky Bentgrass (Apera spica-venti). AB - Herbicide resistance is an example of plant evolution caused by an increased reliance on herbicides with few sites of action to manage weed populations. This micro-evolutionary process depends on fitness, therefore the assessment of fitness differences between susceptible and resistant populations are pivotal to establish management strategies. Loose silky bentgrass (Apera spica-venti) is a serious weed in Eastern, Northern, and Central Europe with an increasing number of herbicide resistant populations. This study examined the fitness and growth characteristics of an ALS resistant biotype. Fitness and growth characteristics were estimated by comparing seed germination, biomass, seed yield and time to key growth stages at four crop densities of winter wheat (0, 48, 96, and 192 plants m 2) in a target-neighborhood design. The resistant population germinated 9-20 growing degree days (GDD) earlier than the susceptible population at 10, 16, and 22 degrees C. No differences were observed between resistant and susceptible populations in tiller number, biomass, time to stem elongation, time to first visible inflorescence and seed production. The resistant population reached the inflorescence emergence and flowering stages in less time by 383 and 196 GDD, respectively, at a crop density of 96 winter wheat plants m-2 with no differences registered at other densities. This study did not observe a fitness cost to herbicide resistance, as often hypothesized. Inversely, a correlation between non target site resistance (NTSR), earlier germination and earlier flowering time which could be interpreted as fitness benefits as these plant characteristics could be exploited by modifying the timing and site of action of herbicide application to better control ALS NTSR populations of A. spica-venti. PMID- 28993788 TI - Lanthanum Inhibits Primary Root Growth by Repressing Auxin Carrier Abundances in Arabidopsis. AB - Lanthanum (La) is one of rare earth elements that was used as a crop growth stimulants; however, high concentration of La markedly inhibited plant growth. Our previous study indicated that, although La induced the expression of auxin biosynthesis-related genes, it markedly repressed primary root (PR) elongation by reducing auxin accumulation in PR tips. In this study, we exhibited that La reduces the abundances of auxin carriers. Treatment with La markedly inhibited the auxins IAA-, 2,4-D-, and NAA-induced elevation of DR5:GUS activity in the roots, suggesting that La inhibited auxin transport through both the influx and efflux transporters. Supplementation with auxin transport inhibitor naphthylphthalamic acid in La-treated seedlings did not further reduce PR growth compared with that of the La treatment alone, further confirmed that auxin transport is involved in La-induced inhibition of PR growth. Analysis of the protein abundances using the transgenic AUX1-YFP and PIN1/2/4/7-GFP marker lines indicated that La treatment reduced the abundances of all these auxin carriers in the PR tips. La also increased the stabilization of Aux/IAA protein AXR3. Taken together, these results indicated that La treatment inhibits PIN-mediated auxin transport and subsequently impairs auxin distribution and PR growth via reducing auxin carrier abundances. PMID- 28993789 TI - Editorial: Melatonin in Plants. PMID- 28993790 TI - Network Diffusion-Based Prioritization of Autism Risk Genes Identifies Significantly Connected Gene Modules. AB - Autism spectrum disorder (ASD) is marked by a strong genetic heterogeneity, which is underlined by the low overlap between ASD risk gene lists proposed in different studies. In this context, molecular networks can be used to analyze the results of several genome-wide studies in order to underline those network regions harboring genetic variations associated with ASD, the so-called "disease modules." In this work, we used a recent network diffusion-based approach to jointly analyze multiple ASD risk gene lists. We defined genome-scale prioritizations of human genes in relation to ASD genes from multiple studies, found significantly connected gene modules associated with ASD and predicted genes functionally related to ASD risk genes. Most of them play a role in synapsis and neuronal development and function; many are related to syndromes that can be in comorbidity with ASD and the remaining are involved in epigenetics, cell cycle, cell adhesion and cancer. PMID- 28993791 TI - A Flow Cytometry Protocol to Estimate DNA Content in the Yellowtail Tetra Astyanax altiparanae. AB - The production of triploid yellowtail tetra Astyanax altiparanae is a key factor to obtain permanently sterile individuals by chromosome set manipulation. Flow cytometric analysis is the main tool for confirmation of the resultant triploids individuals, but very few protocols are specific for A. altiparanae species. The current study has developed a protocol to estimate DNA content in this species. Furthermore, a protocol for long-term storage of dorsal fins used for flow cytometry analysis was established. The combination of five solutions with three detergents (Nonidet P-40 Substitute, Tween 20, and Triton X-100) at 0.1, 0.2, and 0.4% concentration was evaluated. Using the best solution from this first experiment, the addition of trypsin (0.125, 0.25, and 0.5%) and sucrose (74 mM) and the effects of increased concentrations of the detergents at 0.6 and 1.2% concentration were also evaluated. After adjustment of the protocol for flow cytometry, preservation of somatic tissue or isolated nuclei was also evaluated by freezing (at -20 degrees C) and fixation in saturated NaCl solution, acetic methanol (1:3), ethanol, and formalin at 10% for 30 or 60 days of storage at 25 degrees C. Flow cytometry analysis in yellowtail tetra species was optimized using the following conditions: lysis solution: 9.53 mM MgCl2.7H20; 47.67 mM KCl; 15 mM Tris; 74 mM sucrose, 0.6% Triton X-100, pH 8.0; staining solution: Dulbecco's PBS with DAPI 1 MUg mL-1; preservation procedure: somatic cells (dorsal fin samples) frozen at -20 degrees C. Using this protocol, samples may be stored up to 60 days with good accuracy for flow cytometry analysis. PMID- 28993792 TI - The price of whole-genome sequencing may be decreasing, but who will be sequenced? AB - AIM: Since whole-genome sequencing (WGS) information can have positive and negative personal utility for individuals, we examined predictors of willingness to pay (WTP) for WGS. PATIENTS & METHODS: We surveyed two independent populations: adult patients (n = 203) and college seniors (n = 980). Ordinal logistic regression models were used to characterize the relationship between predictors and WTP. RESULTS: Sex, age, education, income, genomic knowledge and knowing someone who had genetic testing or having had genetic testing done personally were associated with significantly higher WTP for WGS. After controlling for income and education, males were willing to pay more for WGS than females. CONCLUSION: Differences in WTP may impact equity, coverage, affordability and access, and should be anticipated by public dialog about related health policy. PMID- 28993793 TI - Chiral Organic Dyes Endowed with Circularly Polarized Laser Emission. AB - The direct generation of efficient, tunable, and switchable circularly polarized laser emission (CPLE) would have far-reaching implications in photonics and material sciences. In this paper, we describe the first chiral simple organic molecules (SOMs) capable of simultaneously sustaining significant chemical robustness, high fluorescence quantum yields, and circularly polarized luminescence (CPL) ellipticity levels (|glum|) comparable to those of similar CPL SOMs. All these parameters altogether enable efficient laser emission and CPLE with ellipticity levels 2 orders of magnitude stronger than the intrinsic CPL ones. PMID- 28993794 TI - Antitrypanosomal and antileishmanial activity of prenyl-1,2,3-triazoles. AB - A series of prenyl 1,2,3-triazoles were prepared from isoprenyl azides and different alkynes. The dipolar cycloaddition reaction provided exclusively primary azide products as regioisomeric mixtures that were separated by column chromatography and fully characterized. Most of the compounds displayed antiparasitic activity against Trypanosoma cruzi and Leishmania donovani. The most active compounds were assayed as potential TcCYP51 inhibitors. PMID- 28993796 TI - Supporting Evidence-Based National Cancer Control Planning: The Asia-Pacific Phase II Leadership Forum. PMID- 28993795 TI - Reactive Carbonyl Species Scavengers-Novel Therapeutic Approaches for Chronic Diseases. AB - PURPOSE OF THE REVIEW: To summarize recent evidence supporting the use of reactive carbonyl species scavengers in the prevention and treatment of disease. RECENT FINDINGS: The newly developed 2-aminomethylphenol class of scavengers shows great promise in preclinical trials for a number of diverse conditions including neurodegenerative diseases and cardiovascular disease. In addition, new studies with the thiol-based and imidazole-based scavengers have found new applications outside of adjunctive therapy for chemotherapeutics. SUMMARY: Reactive oxygen species (ROS) generated by cells and tissues act as signaling molecules and as cytotoxic agents to defend against pathogens, but ROS also cause collateral damage to vital cellular components. The polyunsaturated fatty acyl chains of phospholipids in the cell membranes are particularly vulnerable to damaging peroxidation by ROS. Evidence suggests that the breakdown of these peroxidized lipids to reactive carbonyls species plays a critical role in many chronic diseases. Antioxidants that abrogate ROS-induced formation of reactive carbonyl species also abrogate normal ROS signaling and thus exert both beneficial and adverse functional effects. The use of scavengers of reactive dicarbonyl species represent an alternative therapeutic strategy to potentially mitigate the adverse effects of ROS without abrogating normal signaling by ROS. In this review, we focus on three classes of reactive carbonyl species scavengers: thiol-based scavengers (2-mercaptoethanesulfonate and amifostine), imidazole-based scavengers (carnosine and its analogs), and 2-aminomethylphenols based scavengers (pyridoxamine, 2-hydroxybenzylamine, and 5'-O-pentyl pyridoxamine) that are either undergoing pre-clinical studies, advancing to clinical trials, or are already in clinical use. PMID- 28993797 TI - The Linkage between Breast Cancer, Hypoxia, and Adipose Tissue. AB - OBJECTIVE: The development of breast cancer cells is linked to hypoxia. The hypoxia-induced factor HIF-1alpha influences metastasis through neovascularization. Hypoxia seems to decrease the responsiveness to hormonal treatment due to loss of estrogen receptors (ERs). Obesity is discussed to increase hypoxia in adipocytes, which promotes a favorable environment for tumor cells in mammary fat tissue, whereas, tumor cells profit from good oxygen supply and are influenced by its deprivation as target regions within tumors show. This review gives an overview of the current state on research of hypoxia and breast cancer in human adipose tissue. METHODS: A systematic literature search was conducted on PubMed (2000-2016) by applying hypoxia and/or adipocytes and breast cancer as keywords. Review articles were excluded as well as languages other than English or German. There was no restriction regarding the study design or type of breast cancer. A total of 35 papers were found. Eight studies were excluded due to missing at least two of the three keywords. One paper was removed due to Russian language, and one was dismissed due to lack of adherence. Seven papers were identified as reviews. After applying exclusion criteria, 18 articles were eligible for inclusion. RESULTS: Two articles describe the impairment of mammary epithelial cell polarization through hypoxic preconditioning. A high amount of adipocytes enhances cancer progression due to the increased expression of HIF 1alpha which causes the loss of ER alpha protein as stated in four articles. Four articles analyzed that increased activation of HIF's induces a series of transcriptions resulting in tumor angiogenesis. HIF inhibition, especially when combined with cytotoxic chemotherapy, holds strong potential for tumor suppression as stated in further four articles. In two articles there is evidence of a strong connection between hypoxia, oxidative stress and a poor prognosis for breast cancer via HIF regulated pathways. Acute hypoxia seems to normalize the microenvironment in breast cancer tissue and has proven to affect tumor growth positively as covered in two articles. CONCLUSION: This review indicates that the development of breast cancer is influenced by hypoxia. A high amount of adipocytes enhances cancer progression due to the increased expression of HIF 1alpha. PMID- 28993798 TI - Challenges for Quality Assurance of Target Volume Delineation in Clinical Trials. AB - In recent years, new radiotherapy techniques have emerged that aim to improve treatment outcome and reduce toxicity. The standard method of evaluating such techniques is to conduct large scale multicenter clinical trials, often across continents. A major challenge for such trials is quality assurance to ensure consistency of treatment across all participating centers. Analyses from previous studies have shown that poor compliance and protocol violation have a significant adverse effect on treatment outcomes. The results of the clinical trials may, therefore, be confounded by poor quality radiotherapy. Target volume delineation (TVD) is one of the most critical steps in the radiotherapy process. Many studies have shown large inter-observer variations in contouring, both within and outside of clinical trials. High precision techniques, such as intensity-modulated radiotherapy, image-guided brachytherapy, and stereotactic radiotherapy have steep dose gradients, and errors in contouring may lead to inadequate dose to the tumor and consequently, reduce the chance of cure. Similarly, variation in organ at risk delineation will make it difficult to evaluate dose response for toxicity. This article reviews the literature on TVD variability and its impact on dosimetry and clinical outcomes. The implications for quality assurance in clinical trials are discussed. PMID- 28993799 TI - Genetic Characterization of Brain Metastases in the Era of Targeted Therapy. AB - In the current era of molecularly targeted therapies and precision medicine, choice of cancer treatment has been increasingly tailored according to the molecular or genomic characterization of the cancer the individual has. Previously, the clinical observation of inadequate control of brain metastases was widely attributed to a lack of central nervous system (CNS) penetration of the anticancer drugs. However, more recent data have suggested that there are genetic explanations for such observations. Genomic analyses of brain metastases and matching primary tumor and other extracranial metastases have revealed that brain metastases can harbor potentially actionable driver mutations that are unique to them. Identification of genomic alterations specific to brain metastases and targeted therapies against these mutations represent an important research area to potentially improve survival outcomes for patients who develop brain metastases. Novel approaches in genomic testing such as that using cell free circulating tumor DNA (ctDNA) in the cerebrospinal fluid (CSF) facilitate advancing our understanding of the genomics of brain metastases, which is critical for precision medicine. CSF-derived ctDNA sequencing may be particularly useful in patients who are unfit for surgical resection or have multiple brain metastases, which can harbor mutations that are distinct from their primary tumors. Compared to the traditional chemotherapeutics, novel targeted agents appear to be more effective in controlling the CNS disease with better safety profiles. Several brain metastases-dedicated trials of various targeted therapies are currently underway to address the role of these agents in the treatment of CNS disease. This review focuses on recent advances in genomic profiling of brain metastases and current knowledge of targeted therapies in the management of brain metastases from cancers of the breast, lung, colorectum, kidneys, and ovaries as well as melanoma. PMID- 28993801 TI - Obesity-Related Hypertension in Children. AB - Obesity and hypertension have both been on the rise in children. Each is associated with increased cardiovascular disease risk and both track into adulthood, increasing the prevalence of heart disease and related morbidity and mortality. All children should be screened for hypertension, but children with comorbid obesity may not only particularly benefit from the screening but may also prove the most challenging to screen. Increased arm circumference and conical arm shape are particularly problematic when attempting to obtain an accurate blood pressure (BP) measurement. This review focuses on the unique aspects of hypertension evaluation and management in the child with comorbid obesity. Specific traditional and non-traditional risk factors that may contribute to elevated BP in children with obesity are highlighted. Current proposed pathophysiologic mechanisms by which obesity may contribute to elevated BP and hypertension is reviewed, with focus on the role of the sympathetic nervous system and the renin-angiotensin-aldosterone system. This review also presents a targeted treatment approach to children with obesity-related hypertension, providing evidence for the recommended therapeutic lifestyle change that should form the basis of any antihypertensive treatment plan in this population of at-risk children. Advantages of specific pharmacologic agents in the treatment of obesity-related hypertension are also reviewed. PMID- 28993800 TI - Gene Duplication and Protein Evolution in Tick-Host Interactions. AB - Ticks modulate their hosts' defense responses by secreting a biopharmacopiea of hundreds to thousands of proteins and bioactive chemicals into the feeding site (tick-host interface). These molecules and their functions evolved over millions of years as ticks adapted to blood-feeding, tick lineages diverged, and host shifts occurred. The evolution of new proteins with new functions is mainly dependent on gene duplication events. Central questions around this are the rates of gene duplication, when they occurred and how new functions evolve after gene duplication. The current review investigates these questions in the light of tick biology and considers the possibilities of ancient genome duplication, lineage specific expansion events, and the role that positive selection played in the evolution of tick protein function. It contrasts current views in tick biology regarding adaptive evolution with the more general view that neutral evolution may account for the majority of biological innovations observed in ticks. PMID- 28993802 TI - Glycemia Is Related to Impaired Cerebrovascular Autoregulation after Severe Pediatric Traumatic Brain Injury: A Retrospective Observational Study. AB - INTRODUCTION: A strong association exists between hyperglycemia and outcome in pediatric traumatic brain injury (TBI). Herein, we describe observations of serum markers of glucose metabolism in a cohort of pediatric TBI patients and how these variables are related to parameters of intracranial pathophysiology. METHODS: A retrospective analysis was performed on pediatric severe TBI patients admitted to Addenbrookes Hospital Paediatric Intensive Care Unit (PICU) between January 2001 and December 2013. Demographic, outcome, systemic physiological, and cerebral autoregulatory data were extracted for patients who had received continuous invasive monitoring (ICM+, Cambridge Enterprise, Cambridge, UK). Data were analyzed using a mixed linear model. RESULTS: Forty-four patients with an average age of 12.2 years were admitted to the PICU with a TBI requiring invasive neurosurgical monitoring. Thirty-two patients (73%) survived, with favorable outcomes in 62%. The mean (SD) intracranial pressure (ICP) was 17.6 + 9.0 mmHg, MAP was 89.7 + 9.0 mmHg, and pressure-reactivity index (PRx) was -0.01 + 0.23 a.u. The mean (SD) serum lactate was 2.2 (3.3) mmol/L. and the mean (SD) serum glucose was 6.1 (1.6) mmol/L. Early hyperglycemia was strongly associated with both PRx (Pearson correlation 0.351, p < 0.001) and ICP (Pearson correlation 0.240, p = 0.002) death (p = 0.021) and impaired cerebral autoregulation (p = 0.02). There was a strong association between ICP and serum lactate (p = 0.001). CONCLUSION: Increases in systemic glucose are associated with impaired cerebrovasular autoregulation after severe pediatric TBI. Moreover, deranged blood glucose is a marker of poor prognosis. Further studies are required to delineate putative mechanisms of hyperglycemia induced cerebral harm. PMID- 28993803 TI - Opinion: "Heart Rate Variability, Health and Well-Being: A Systems Perspective" Research Topic. PMID- 28993804 TI - Familial Hypercholesterolemia: A Systematic Review of Guidelines on Genetic Testing and Patient Management. AB - BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal-dominant hereditary disorder of lipid metabolism that causes lifelong exposure to increased LDL levels resulting in premature coronary heart disease and, if untreated, death. Recent studies have shown its prevalence to be higher than previously considered, which has important implications for the mortality and morbidity of associated cardiovascular disease (CVD). Several clinical tools are used worldwide to help physicians diagnose FH, but nevertheless most patients remain undetected. This systematic review of guidelines aims to assess the role of genetic testing in the screening, diagnosis, and management of patients affected by heterozygous or homozygous FH and to identify related health-care pathways. METHODS: We performed a systematic review of the literature; inclusion criteria were English or Italian guidelines focusing on genetic testing. The guidelines were included and evaluated for their content and development process using the Appraisal of Guidelines for Research and Evaluation II instrument. RESULTS: Ten guidelines were considered eligible, and all were judged to be of good quality, with slight differences among them. The most common indications for performing genetic tests were high levels of cholesterol, or physical findings consistent with lipid disorder, in the subject or in the family history. Subsequent screening of family members was indicated when a mutation had been identified in the index patient. Regarding patient management, the various guidelines agreed that intensive treatment with lipid-lowering medications should begin as quickly as possible and that lifestyle modifications should be an integral part of the therapy. CONCLUSION: Since the early detection of affected patients is beneficial for effective prevention of CVD, genetic testing is particularly useful for identifying family members via cascade screening and for distinguishing between heterozygous and homozygous individuals, the latter of which require more extreme therapeutic intervention. PMID- 28993805 TI - Addressing Pressing Needs in the Development of Advanced Therapies. AB - The commercial development of advanced therapy medicinal products (ATMPs) represents great opportunity for therapeutic innovation but is beset by many challenges for its developers. Although the ATMP field continues to progress at a rapid pace, evidenced by the increasing number of clinical trials conducted over the past few years, several factors continue to complicate the introduction of ATMPs as a curative treatment for multiple disease types, by blocking their translational pathway from research to the patient. While several recent publications (Trounson and McDonald, 2015; Abou-El-Enein et al., 2016a,b) as well as an Innovative Medicines Initiative consultation (IMI, 2016) this year have highlighted the major gaps in ATMP development, with manufacturing, regulatory, and reimbursement issues at the forefront, there remains to be formulated a coherent strategy to address these by bringing the relevant stakeholders to a single forum, whose task it would be to design and execute a delta plan to alleviate the most pressing bottlenecks. This article focuses on two of the most urgent areas in need of attention in ATMP development, namely manufacturing and reimbursement, and promotes the concept of innovation-dedicated research infrastructures to support a multi-sector approach for ensuring the successful development, entry, and ensuing survival of ATMPs in the healthcare market. PMID- 28993807 TI - Examining Plausibility of Self-Reported Energy Intake Data: Considerations for Method Selection. AB - Self-reported dietary intake data contain valuable information and have long been used in the development of nutrition programs and policy. Some degree of measurement error is always present in such data. Biological plausibility, assessed by determining whether self-reported energy intake (rEI) reflects physiological status and physical activity level, must be examined and accounted for before drawing conclusions about intake. Methods that may be used to account for plausibility of rEI include crude methods such as excluding participants reporting EIs at the extremes of a range of intake and individualized methods such as statistical adjustment and applying cutoffs that account for the errors associated with within-participant variation in EI and total energy expenditure (TEE). These approaches allow researchers to determine how accounting for under- and overreporting affects study results and to appropriately address misreporting in drawing conclusions with data collected and in interpreting reported research. In selecting a procedure to assess and account for plausibility of intake, there are a number of key considerations, such as resources available, the dietary report instrument, as well as the advantages and disadvantages of each method. While additional studies are warranted to recommend one procedure as superior to another, researchers should apply one of the available methods to address the issue of implausible rEI. If no method is applied, then at minimum, mean TEE or rEI/TEE should be reported to allow readers to ascertain the degree of misreporting at a gross level and better interpret the data and results provided. PMID- 28993806 TI - Genetics in Idiopathic Pulmonary Fibrosis Pathogenesis, Prognosis, and Treatment. AB - Idiopathic pulmonary fibrosis (IPF), the most common form of idiopathic interstitial pneumonia (IIP), is characterized by irreversible scarring of the lung parenchyma and progressive decline in lung function leading to eventual respiratory failure. The prognosis of IPF is poor with a median survival of 3-5 years after diagnosis and no curative medical therapies. Although the pathogenesis of IPF is not well understood, there is a growing body of evidence that genetic factors contribute to disease risk. Recent studies have identified common and rare genetic variants associated with both sporadic and familial forms of pulmonary fibrosis, with at least one-third of the risk for developing fibrotic IIP explained by common genetic variants. The IPF-associated genetic loci discovered to date are implicated in diverse biological processes, including alveolar stability, host defense, cell-cell barrier function, and cell senescence. In addition, some common variants have also been associated with distinct clinical phenotypes. Better understanding of how genetic variation plays a role in disease risk and phenotype could identify potential therapeutic targets and inform clinical decision-making. In addition, clinical studies should be designed controlling for the genetic backgrounds of subjects, since clinical outcomes and therapeutic responses may differ by genotype. Further understanding of these differences will allow the development of personalized approaches to the IPF management. PMID- 28993808 TI - MicroRNAs: New Players in the Pathobiology of Preeclampsia. AB - Our understanding of how microRNAs (miRNAs) regulate gene networks and affect different molecular pathways leading to various human pathologies has significantly improved over the years. In contrary, the role of miRNAs in pregnancy-related hypertensive disorders such as preeclampsia (PE) is only beginning to emerge. Recent papers highlight that adverse pregnancy outcomes are associated with aberrant expression of several miRNAs. Presently, efforts are underway to determine the biologic function of these placental miRNAs which can shed light on their contribution to these pregnancy-related disease conditions. The discovery that miRNAs are stable in circulation coupled with the fact that the placenta is capable of releasing them to the circulation in exosomes generates a lot of enthusiasm to use them as biomarkers. In this review, we will summarize the recent findings of our understanding of miRNA regulation in relation to PE, a hypertensive disorder of pregnancy. Particular emphasis will be given to the role of key miRNA molecules such as miR-210 and miR-155 that are known to be consistently dysregulated in women with PE. PMID- 28993809 TI - Characterization of a Multidrug-Resistant Salmonella enterica Serovar Heidelberg Outbreak Strain in Commercial Turkeys: Colonization, Transmission, and Host Transcriptional Response. AB - : In recent years, multidrug-resistant (MDR) Salmonella enterica serovar Heidelberg (S. Heidelberg) has been associated with numerous human foodborne illness outbreaks due to consumption of poultry. For example, in 2011, an MDR S. Heidelberg outbreak associated with ground turkey sickened 136 individuals and resulted in 1 death. In response to this outbreak, 36 million pounds of ground turkey were recalled, one of the largest meat recalls in U.S. HISTORY: To investigate colonization of turkeys with an MDR S. Heidelberg strain isolated from the ground turkey outbreak, two turkey trials were performed. In experiment 1, 3-week-old turkeys were inoculated with 108 or 1010 CFU of the MDR S. Heidelberg isolate, and fecal shedding and tissue colonization were detected following colonization for up to 14 days. Turkey gene expression in response to S. Heidelberg exposure revealed 18 genes that were differentially expressed at 2 days following inoculation compared to pre-inoculation. In a second trial, 1-day old poults were inoculated with 104 CFU of MDR S. Heidelberg to monitor transmission of Salmonella from inoculated poults (index group) to naive penmates (sentinel group). The transmission of MDR S. Heidelberg from index to sentinel poults was efficient with cecum colonization increasing 2 Log10 CFU above the inoculum dose at 9 days post-inoculation. This differed from the 3-week-old poults inoculated with 1010 CFU of MDR S. Heidelberg in experiment 1 as Salmonella fecal shedding and tissue colonization decreased over the 14-day period compared to the inoculum dose. These data suggest that young poults are susceptible to colonization by MDR S. Heidelberg, and interventions must target turkeys when they are most vulnerable to prevent Salmonella colonization and transmission in the flock. Together, the data support the growing body of literature indicating that Salmonella establishes a commensal-like condition in livestock and poultry, contributing to the asymptomatic carrier status of the human foodborne pathogen in our animal food supply. PMID- 28993810 TI - Computed Tomography and Magnetic Resonance Imaging Are Equivalent in Mensuration and Similarly Inaccurate in Grade and Type Predictability of Canine Intracranial Gliomas. AB - While magnetic resonance imaging (MRI) is the gold-standard imaging modality for diagnosis of intracranial neoplasia, computed tomography (CT) remains commonly used for diagnosis and therapeutic planning in veterinary medicine. Despite the routine use of both imaging modalities, comparison of CT and MRI has not been described in the canine patient. A retrospective study was performed to evaluate CT and MRI studies of 15 dogs with histologically confirmed glioma. Multiple lesion measurements were obtained, including two-dimensional and volumetric dimensions in pre-contrast and post-contrast images. Similar measurement techniques were compared between CT and MRI. The glioma type (astrocytoma or oligodendroglioma) and grade (high or low) were predicted on CT and MRI independently. With the exception of the comparison between CT pre-contrast volume to T2-weighted MRI volume, no other statistical differences between CT and MRI measurements were identified. Overall accuracy for tumor grade (high or low) was 46.7 and 53.3% for CT and MRI, respectively. For predicted tumor type, accuracy of CT was 53.3% and MRI and MRI 60%. Based on the results of this study, both CT and MRI contrast measurement techniques are considered equivalent options for lesion mensuration. Given the low-to-moderate predictability of CT and MRI in glioma diagnosis, histopathology remains necessary for accurate diagnosis of canine brain tumors. PMID- 28993811 TI - A New Mining Method to Detect Real Time Substance Use Events from Wearable Biosensor Data Stream. AB - Detecting real time substance use is a critical step for optimizing behavioral interventions to prevent drug abuse. Traditional methods based on self-reporting or urine screening are inefficient or intrusive for drug use detection, and inappropriate for timely interventions. For example, self-report suffers from distortion or recall bias; while urine screening often detects drug use that occurred only within the previous 72 hours. Methods for real-time substance use detection are severely underdeveloped, partly due to the novelty of wearable biosensor technique and the lack of substantive clinical data for evaluation. We propose a new real-time drug use event detection method using data obtained from wearable biosensors. Specifically, this method is built upon the slide window technique to process the data stream, and a distance-based outlier detection method to identify substance use events. This novel method is designed to examine how to detect and set up the thresholds of parameters in real-time drug use event detection for wearable biosensor data streams. Our numerical analyses empirically identified the thresholds of parameters used to detect the cocaine use and showed that this proposed method could be adapted to detect other substance use events. PMID- 28993812 TI - Dynamic Alterations in DNA Methylation Precede Tris(1,3-dichloro-2 propyl)phosphate-Induced Delays in Zebrafish Epiboly. AB - Tris(1,3-dichloro-2-propyl)phosphate (TDCIPP) is an organophosphate flame retardant that impacts zebrafish epiboly - an effect that may be associated with genome-wide hypomethylation. Using zebrafish as a model, the objectives of this study were to (1) quantify concentration-dependent impacts of TDCIPP on epiboly; (2) determine whether co-exposure with folic acid (FA) - a methyl donor - mitigates TDCIPP-induced impacts; and (3) using ten previously identified TDCIPP susceptible loci, rely on bisulfite amplicon sequencing (BSAS) to monitor CpG methylation dynamics across multiple TDCIPP concentrations in the presence or absence of FA. Embryos were exposed to TDCIPP from 0.75 h post-fertilization (hpf) to 2, 4, 6, or 24 hpf in the presence or absence of 1 mM FA. Although TDCIPP delayed epiboly up to 3 h by 6 hpf and induced malformations by 24 hpf, FA was unable to mitigate TDCIPP-induced effects at all stages evaluated. Moreover, while no differences in global methylation were detected using a 5-methylcytosine (5-mC) DNA ELISA, BSAS revealed that TDCIPP-induced effects on CpG methylation were dependent on concentration and developmental stage, and that early effects on methylation do not persist despite continuous exposure. Our findings demonstrate that TDCIPP delays zebrafish epiboly, a phenotype that is preceded by complex, dynamic alterations in DNA methylation. PMID- 28993813 TI - MIFuzzy Clustering for Incomplete Longitudinal Data in Smart Health. AB - Missing data are common in longitudinal observational and randomized controlled trials in smart health studies. Multiple-imputation based fuzzy clustering is an emerging non-parametric soft computing method, used for either semi-supervised or unsupervised learning. Multiple imputation (MI) has been widely-used in missing data analyses, but has not yet been scrutinized for unsupervised learning methods, although they are important for explaining the heterogeneity of treatment effects. Built upon our previous work on MIfuzzy clustering, this paper introduces the MIFuzzy concepts and performance, theoretically, empirically and numerically demonstrate how MI-based approach can reduce the uncertainty of clustering accuracy in comparison to non- and single-imputation based clustering approach. This paper advances our understanding of the utility and strength of MIFuzzy clustering approach to processing incomplete longitudinal behavioral intervention data. PMID- 28993814 TI - A Dopamine Receptor genetic variant enhances perceptual speed in cognitive healthy subjects. AB - Cognition is under strong genetic control, yet the specific genes are unknown. To investigate genetic influences on specific cognitive domains, 153 cognitive healthy subjects of European ancestry from the Reference Abilities Study (RANN) were genotyped for 1,160 variants within 446 neuropsychiatric genes. Adjusted linear regression models evaluated the association between the genetic variants and four reference abilities, which capture variance in age-related cognitive function (Vocabulary, Episodic Memory, Perceptual Speed, and Reasoning). 159 variants nominally significant in the RANN cohort were then re-evaluated in an independent cohort of 868 cognitive healthy subjects from the Religious Orders Study and Rush Memory Aging Project. Meta-analysis yielded a Bonferroni adjusted statistically significant association between perceptual speed and a variant located in the promoter of the dopamine receptor D4 gene, rs3756450 (beta=0.23, SE=0.05, P meta =2.3 * 10-5). Our data suggest that genetic variation in a dopamine pathway gene influences perceptual speed performance in cognitively healthy individuals. PMID- 28993816 TI - Psychological and psychobiological responses to immediate early intervention in the emergency department: Case report of one-session exposure therapy for the prevention of PTSD. AB - Research suggests that exposure therapy provided in the hours immediately following trauma exposure may prevent PTSD development. This case report presents data on an at-risk for PTSD participant involved in a motor-vehicle crash that caused her severe distress. She received one session of exposure therapy in the emergency department (ED) as part of an ongoing randomized controlled study examining the optimal dose of exposure therapy in the immediate aftermath of trauma. PTSD and depression measures were collected at pre-treatment assessment and one- and three-month follow-up. Potential PTSD biomarkers were also examined. Psychophysiological reactions were measured using skin conductance data measured on an iPad during the exposure therapy session and the follow-up assessments. A fear-potentiated startle paradigm and an functional magnetic resonance imaging (fMRI) behavioral inhibition task were used at follow-up. The participant demonstrated subjective and psychophysiological extinction from pre- to post imaginal exposure. At follow-up, she did not meet DSM-IV criteria for PTSD or demonstrate hyperarousal to trauma reminders and showed robust fear extinction and the ability to inhibit responses in an fMRI behavioral inhibition task. In line with previous early intervention for the prevention of PTSD studies, this case report supports the need for ongoing empirical research investigating the possibility that one session of exposure therapy in the ED may attenuate risk for PTSD. Furthermore, the current findings demonstrate psychophysiological extinction serving as a prognostic indicator of treatment response for PTSD early intervention to be an exciting avenue to explore in future systematic research. PMID- 28993815 TI - Membrane Pore Spacing Can Modulate Endothelial Cell-Substrate and Cell-Cell Interactions. AB - Mechanical cues and substrate interaction affect the manner in which cells adhere, spread, migrate and form tissues. With increased interest in tissue-on-a chip and co-culture systems utilizing porous membranes, it is important to understand the role of disrupted surfaces on cellular behavior. Using a transparent glass membrane with defined pore geometries, we investigated endothelial fibronectin fibrillogenesis and formation of focal adhesions as well as development of intercellular junctions. Cells formed fewer focal adhesions and had shorter fibronectin fibrils on porous membranes compared to non-porous controls, which was similar to cell behavior on continuous soft substrates with Young's moduli seven orders of magnitude lower than glass. Additionally, porous membranes promoted enhanced cell-cell interactions as evidenced by earlier formation of tight junctions. These findings suggest that porous membranes with discontinuous surfaces promote reduced cell-matrix interactions similarly to soft substrates and may enhance tissue and barrier formation. PMID- 28993817 TI - Nonworksite Interventions to Reduce Sedentary Behavior among Adults: A Systematic Review. AB - PURPOSE: Sedentary behavior has been identified as a major health risk. While interventions to reduce time spent sedentary have become increasingly prevalent, the vast majority of this work in adults has been focused on workplace sedentary behavior, and often pairs sedentary reduction interventions with increasing physical activity. As research designed to specifically decrease sedentary time that is not limited to the workplace becomes available, identifying strategies and approaches, along with feasibility and efficacy of these interventions, is warranted. METHODS: Electronic databases were searched for sedentary interventions with eligibility criteria including: (a) interventions designed to explicitly reduce sedentary behavior that were not limited to the workplace, (b) outcomes specific to sedentary behavior, (c) adults aged at least 18 years, and (d) written in English. RESULTS: A total of 767 full-text manuscripts were identified, with thirteen studies meeting all eligibility criteria. While intervention characteristics and methodological quality varied greatly among studies, ten of the thirteen studies observed a significant reduction in objectively measured sitting time post-intervention. In those studies that collected participant feasibility/acceptability data, all reported that the intervention was viewed as "favorable to very favorable," would use again, and that participant burden was quite low, suggesting that these interventions were feasible. CONCLUSION: Sedentary behavior interventions not limited to the workplace appear to be largely efficacious. While results varied with respect to the magnitude of the decrease in time spent sedentary, they are encouraging. However, due to the small body of evidence and the variability of study designs, our ability to make overarching statements regarding "best practices" at this time is limited. Well-controlled trials of longer duration with larger samples, using theoretically-based interventions with consistent prescriptions for limiting sedentary time are needed. PMID- 28993818 TI - Metabotropic Glutamate Receptor 5 and Glutamate Involvement in Major Depressive Disorder: A Multimodal Imaging Study. AB - BACKGROUND: Preclinical and postmortem studies have implicated the metabotropic glutamate receptor 5 (mGluR5) in the pathophysiology of major depressive disorder (MDD). The goal of the present study was to determine the role of mGluR5 in a large group of individuals with MDD compared to healthy controls (HC) in vivo with [18F]FPEB and positron emission tomography (PET). Furthermore, we sought to determine the role glutamate plays on mGluR5 availability in MDD. METHODS: Sixty five participants (30 MDD and 35 HC) completed [18F]FPEB PET to estimate the primary outcome measure - mGluR5 volume of distribution (VT), and the secondary outcome measure - mGluR5 distribution volume ratio (DVR). A subgroup of 39 participants (16 MDD and 23 HC) completed proton magnetic resonance spectroscopy (1H MRS) to estimate anterior cingulate (ACC) glutamate, glutamine, and Glx (glutamate + glutamine) levels relative to creatine (Cr). RESULTS: No significant between-group differences were observed in mGluR5 VT or DVR. Compared to HC, individuals with MDD had higher ACC glutamate, glutamine, and Glx levels. Importantly, the ACC mGluR5 DVR negatively correlated with glutamate/Cr and Glx/Cr levels. CONCLUSIONS: In this novel in vivo examination, we show an inverse relationship between mGluR5 availability and glutamate levels. These data highlight the need to further investigate the role of glutamatergic system in depression. PMID- 28993820 TI - Editorial: Is the Current Periodontitis Classification Supported by Pathophysiological Evidence? PMID- 28993819 TI - Vigilance, the Amygdala, and Anxiety in Youths with a History of Institutional Care. AB - BACKGROUND: Early adversity is commonly associated with alterations of amygdala circuitry and increased anxiety. While many theoretical and clinical accounts of early adversity suggest that it increases vigilance to threatening stimuli, the present study tested whether heightened anxiety and amygdala reactivity associated with early adversity enhanced goal-directed attention for threatening stimuli. Showing this association would provide support that these adversity induced alterations are developmental adaptations of the individual. METHODS: 34 children and adolescents who experienced early adversity in the form of previous institutionalization (PI) (26 female, mean age=13.49 years) and a comparison group of 33 children and adolescents who were reared by their biological parents since birth (16 female, mean age=13.40 years) underwent fMRI scanning while completing a visual search task that involved quickly locating a negative (fearful face) or positive target (happy face) in an array of neutral distractor stimuli (neutral faces). RESULTS: Across both groups, individual differences in vigilant behavior were positively associated with amygdala responses for negative versus positive stimuli. However, a moderation analysis revealed that the degree to which amygdala responses were greater for negative versus positive stimuli was associated with greater anxiety symptomology for PI youth, but not comparison youth. CONCLUSIONS: Together, these findings suggest that institutional care strengthens linkages between amygdala reactivity and anxiety, perhaps serving to enhance goal-directed attention. The findings are discussed as both adaptations as well as risk to the individual. PMID- 28993821 TI - Control of Plaque and Gingivitis by an Herbal Toothpaste - A Randomised Controlled Study. AB - PURPOSE: To compare the efficacy of an herbal toothpaste with two other chemically active toothpastes regarding plaque and gingivitis control. MATERIALS AND METHODS: Seventy-six (27 females and 49 males, mean age 47.8 years, range 40 58 years) of 84 initial participants with slight and moderate chronic periodontitis used standardised manual toothbrushes and their usual technique for daily manual mechanical plaque control for 24 weeks of supportive periodontal therapy. The volunteers were randomly assigned to one of 3 groups: group 1 used the herbal toothpaste, group 2 a triclosan/copolymer toothpaste, and group 3 an amine/stannous fluoride toothpaste. OHI, API, SBI, BOP, PD and AL were recorded at baseline and after 6, 12 and 24 weeks (PD and AL only at baseline). The Kruskal-Wallis, Mann-Whitney U-, Friedman, and Wilcoxon tests were used for statistical analysis. RESULTS: Moderate changes occurred in API and OHI in all groups. The herbal toothpaste resulted in significantly lower API and OHI in comparison to the fluoride toothpaste during the study period (p = 0.001 and 0.049, minimum and maximum of cases, respectively). SBI was significantly improved in all groups starting after 12 weeks (p = 0.001 and 0.033). BOP remained largely unchanged in all groups and was always significant lower in the herbal toothpaste group (p = 0.001 and 0.036). CONCLUSION: During the study period of 24 weeks, the herbal toothpaste was as good as the control toothpastes. No side effects were seen. In terms of improving periodontal conditions, the tested herbal toothpaste could be a suitable alternative to conventional toothpastes with artificial chemical ingredients. PMID- 28993822 TI - Survey of Caries Experience in 3- to 5-year-old Children in Northeast Italy in 2011 and Its Trend 1984-2011. AB - PURPOSE: To describe dental caries experience by age and gender among preschool children in a health district in northeast Italy and to plot a trend of primary dentition dental caries prevalence and severity over a 27-year time span (1984 2011). MATERIALS AND METHODS: In a cross-sectional survey, 27 out of 88 kindergartens were randomly selected with a sample of 2603 preschoolers drawn from a population of 8328 3-, 4- and 5-year-old children. Dental caries (d3 t) experience according to the criteria of the British Association for the Study of Community Dentistry was evaluated by two calibrated examiners at schools in 1960 (75.3%) 3- to 5-year-old children from October 2010 to May 2011. Three previous surveys performed in the same area, applying the criteria of the World Health Organization, were used to plot a trend over a 27-year period. Comparisons between groups were made using Pearson's chi-squared test, and caries occurrence was established by logistic regression analysis to assess the influence of sex and age (independent variables) on caries experience (dependent variable). RESULTS: Prevalence (%) and severity (mean dmft +/- SD) increased with age (17% and 0.5 +/- 1.7 at age 3; 24% and 0.8 +/- 2.2 at age 4; 35% and 1.3 +/- 2.6 at age 5). The level of untreated caries was 85.8%. No statistically significant difference was found for gender. From 1984 to 2004, the prevalence and severity of caries declined at all examined ages, but were unchanged from 2004 to 2011. CONCLUSION: The current caries scores in preschoolers are low and similar to those reported in other western European countries. Nevertheless, as very early childhood is a key opportunity to intervene, an effort must be made to provide clear oral health guidance and increase the cooperation among all health professionals. PMID- 28993823 TI - Comment on "Glycine-functionalized copper(ii) hydroxide nanoparticles with high intrinsic superoxide dismutase activity" by K. Korschelt, R. Ragg, C. S. Metzger, M. Kluenker, M. Oster, B. Barton, M. Panthofer, D. Strand, U. Kolb, M. Mondeshki, S. Strand, J. Brieger, M. N. Tahir and W. Tremel, Nanoscale, 2017, 9, 3952. AB - Detoxification of cigarette smoke employing copper compounds has a potential for the formation of polychlorinated dibenzo-p-dioxins and dibenzofurans and should not be practiced before the degree of formation has been shown to be harmless. PMID- 28993824 TI - The ideal porous structure of EDLC carbon electrodes with extremely high capacitance. AB - We propose an ideal porous structure of carbon electrodes for electric double layer capacitors (EDLCs). The porous carbon successfully improved the gravimetric capacitance above ~200 F g-1 even in an organic electrolyte by utilizing the carbon nanopore surface more effectively. High-resolution transmission electron microscopy images and X-ray diffraction patterns classified 15 different porous carbon electrodes into slit-shape and worm-like-shape, and the pore size distributions of the carbons were carefully determined applying the grand canonical Monte Carlo method to N2 adsorption isotherms at 77 K. The ratio of pores where solvated ions and/or desolvated ions can penetrate also has a significant effect on the EDL capacitance as well as the pore shape. The detailed study on the effect of porous morphologies on the EDLC performance indicates that a hierarchical porous structure with a worm-like shaped surface and a pore size ranging from a solvated ion to a solvent molecule is an ideal electrode structure. PMID- 28993825 TI - A transparent CdS@TiO2 nanotextile photoanode with boosted photoelectrocatalytic efficiency and stability. AB - In the present work, we report the exploration of a transparent CdS@TiO2 nanotextile photoanode with boosted photoelectrocatalytic (PEC) efficiency and stability, by the controllable coating of an amorphous TiO2 ultrathin layer via the atomic layer deposition (ALD) technique. The optimal CdS@TiO2 nanotextile photoanode with a 3.5 nm TiO2 ultrathin layer exhibits a photocurrent density of 1.8 mA cm-2 at 0 V vs. RHE, which is 11 times higher than that of the pristine CdS counterpart. The photocatalytic H2 evolution rate of CdS@TiO2 ranges up to 47.5 mmol g-1 h-1, which is superior to those reported for one-dimensional CdS based counterparts. Moreover, the photocurrent of CdS@TiO2 nanotextile photoanodes shows only 9% decay after 9 h, suggesting its profoundly enhanced PEC stability, in comparison with that of pristine CdS photoanodes (almost down to zero after 3 hours). It is verified that the introduced TiO2 nanoshells could limit the charge recombination, facilitate the charge separation, reduce the charge transfer resistance, and enhance the wettability of the electrodes, resulting in their significantly enhanced PEC performance. PMID- 28993826 TI - Effect of size and curvature on the enzyme activity of bionanoconjugates. AB - Biotic-abiotic hybrids comprised of globular proteins and functional nanostructures with complementary and synergistic properties are central to a number of bionanotechnological applications. A comprehensive understanding of the effect of physicochemical properties of abiotic nanostructures on the biological activity of the bionanoconjugates is critical in the design of these bio-nano hybrids. In this study, using size and curvature-controlled gold nanoparticles as a model abiotic system, we investigated the effect of hydrodynamic diameter and surface curvature on the activity of a model enzyme, horseradish peroxidase (HRP), adsorbed on the surface of the nanostructures. In contrast with the previous studies, we have employed a novel class of gold superstructures (gold nanoparticles on spheres) to deconvolute the effects of size and curvature on the catalytic activity of the bionanoconjugates. This study improves our understanding of the bio/nano interface and the design of bioinorganic hybrids with potential applications in biomimetic and bioenabled sensors, energy harvesting, optoelectronic components and devices, responsive and autonomous materials. PMID- 28993827 TI - Synthesis and biological evaluation of novel teixobactin analogues. AB - The cyclic depsipeptide, teixobactin, possesses promising activity against a range of antimicrobial-resistant (AMR) pathogenic bacteria, including Staphylococcus aureus and Mycobacterium tuberculosis. Teixobactin contains a number of non-canonical residues, including the synthetically challenging amino acid, l-allo-enduracididine, complicating clinical application of this peptide. Herein, we report the synthesis of six analogues of teixobactin, in which the non canonical l-allo-enduracididine amino acid is replaced by isosteric, commercially available Fmoc-amino acid building blocks. Biological evaluation of the analogues has revealed promising activity, particularly for guanidine isosteres, against AMR strains of S. aureus and Enterococcus faecalis, highlighting the potential for this class of cyclic depsipeptides in the treatment of Gram-positive infections. PMID- 28993828 TI - Deep convolutional neural networks for Raman spectrum recognition: a unified solution. AB - Machine learning methods have found many applications in Raman spectroscopy, especially for the identification of chemical species. However, almost all of these methods require non-trivial preprocessing such as baseline correction and/or PCA as an essential step. Here we describe our unified solution for the identification of chemical species in which a convolutional neural network is trained to automatically identify substances according to their Raman spectrum without the need for preprocessing. We evaluated our approach using the RRUFF spectral database, comprising mineral sample data. Superior classification performance is demonstrated compared with other frequently used machine learning algorithms including the popular support vector machine method. PMID- 28993829 TI - Structural stability and uniformity of magnetic Pt13 nanoparticles in NaY zeolite. AB - Based on first-principles calculations, the structural stability and magnetic variety of Pt13 nanoparticles encapsulated in a NaY zeolite are investigated. Among 50 stable isomers in the gas phase, due to geometrical constraints, only about 1/3 of those clusters can be inserted in the zeolite pores. Severe structural rearrangements occur depending on whether the solid angle at the Pt vertex bound to the super-cage is larger than 2 sr (i.e., icosahedron). The most relevant example is the structural instability of the icosahedron and, when including van der Waals dispersion forces the opening of the gas phase global minimum moves towards a new L-shaped cubic wire, otherwise unstable. The total magnetisation of the encapsulated Pt13 decreases due to the stabilisation of less coordinated isomers, with the majority of clusters characterised by a total magnetisation of 2MUB, while the majority of free clusters exhibit a threefold value. This analysis allows the understanding of the magnetic behaviour observed in recent experiments through the variety of the isomers which can be accommodated in the zeolite pore. PMID- 28993830 TI - [Tumors of the sensory organs]. PMID- 28993832 TI - [Diagnostics and treatment of primary hyperparathyroidism]. AB - Primary hyperparathyroidism is a disease that occurs more frequently than generally thought and is often overlooked. Classical symptoms are bone pain and osteoporosis, renal calculi and peptic ulcers. Many patients are asymptomatic or have unspecific complaints. It is easy to establish the biochemical diagnosis based on calcium and parathormone (PTH) levels and 24-h urine calcium excretion. The most sensitive localization procedures for parathyroid adenomas are sonography and Tc-99m-MIBI scintigraphy. The indication for surgery is undisputed in symptomatic patients; however, there is controversy concerning patients without classical symptoms. Operative therapy is highly successful. Focused operative procedures are currently available besides the traditional 4-gland exploration. When focused techniques are used, the operative success should be confirmed by intraoperative determination of the parathormone level. PMID- 28993831 TI - Association of SNPs/haplotypes in promoter of TNF A and IL-10 gene together with life style factors in prostate cancer progression in Indian population. AB - OBJECTIVE: Levels of proinflammatory (TNF A) and anti-inflammatory (IL-10) cytokines play a key role in the progression of inflammation as well as cancer disease. We were investigating the potential association of single-nucleotide polymorphisms (SNPs)/haplotypes in proinflammatory (TNF A) and anti-inflammatory (IL-10) cytokines locus with the development of PCa in Indian population. MATERIALS AND METHODS: We had genotyped 235 BPH/PCa samples (130 BPH and 105 cancer) along with 115 control samples for proinflammatory (TNF A -238G/A and 308G/A) and anti-inflammatory (IL-10 -1082A/G, -819C/T and -592C/A) cytokines SNPs in the gene promoter region using ARMS-PCR method. RESULTS: Allelic frequencies of TNF A and IL-10 SNPs were found to be significantly associated with the risk of prostate cancer and BPH when compared to controls (p = 0.05). Further haplotypic analysis showed that two haplotypes of TNF A (AG and AA) and IL-10 gene (CCG and CTG) were serving as risk haplotypes for prostate cancer development. IL-10 risk haplotypes were found to be positively associated with aggressiveness of prostate cancer. We also noticed successively increasing percentage of TNF A and IL-10 risk haplotypes with life style habits like smoking (10 and 26%) and alcohol consuming (9 and 27%). CONCLUSIONS: According to our data, TNF A -238G>A and IL-10 -1082A>G, -819C>T and -592C>A may be associated with the development of prostate cancer and BPH. We could also notice higher frequency of TNF A and IL-10 risk haplotypes in smoker and alcohol user. Interestingly, IL-10 risk haplotype was positively associated with aggressiveness of tumor. This information can be used for the early diagnosis of disease and to improve tissue-specific treatment's efficacy which will be moving ultimately towards the discovery of personalized therapy. PMID- 28993835 TI - Delta Opioid Receptors and Modulation of Mood and Emotion. AB - Depression is a pervasive and debilitating mental disorder that is inadequately treated by current pharmacotherapies in a majority of patients. Although opioids have long been known to regulate mood states, the use of opioids to treat depression is rarely discussed. This chapter explores the preclinical and clinical evidence supporting the antidepressant-like effects of opioid ligands, and in particular, delta opioid receptor (DOR) agonists. DOR agonists have been shown to produce antidepressant-like effects in a number of animal models. Some DOR agonists also produce convulsions which has limited their clinical utility. However, DOR agonists that generate antidepressant-like effects without convulsions have recently been developed and these drugs are beginning to be evaluated in humans. Work investigating potential mechanisms of action for the antidepressant-like effects of DOR agonists is also explored. Understanding mechanisms that give rise to DOR-mediated behaviors is critical for the development of DOR drugs with improved safety and clinical utility, and future work should be devoted to elucidating these pathways. PMID- 28993833 TI - Do anti-stroma therapies improve extrinsic resistance to increase the efficacy of gemcitabine in pancreatic cancer? AB - Pancreatic ductal adenocarcinoma (PDAC) is among the most devastating human malignancies, with approximately 20-30% of PDAC patients receiving the surgical resection with curative intent. Although many studies have focused on finding ideal "drug chaperones" that facilitate and/or potentiate the effects of gemcitabine (GEM) in pancreatic cancer, a significant benefit in overall survival could not be demonstrated for any of these combination therapies in PDAC. Given that pancreatic cancer is characterized by desmoplasia and the dual biological roles of stroma in pancreatic cancer, we reassess the importance of stroma in GEM based therapeutic approaches in light of current findings. This review is focused on understanding the role of stromal components in the extrinsic resistance to GEM and whether anti-stroma therapies have a positive effect on the GEM delivery. This work contributes to the development of novel and promising combination GEM based regimens that have achieved significant survival benefits for the patients with pancreatic cancer. PMID- 28993834 TI - iPSC-derived neural precursor cells: potential for cell transplantation therapy in spinal cord injury. AB - A number of studies have demonstrated that transplantation of neural precursor cells (NPCs) promotes functional recovery after spinal cord injury (SCI). However, the NPCs had been mostly harvested from embryonic stem cells or fetal tissue, raising the ethical concern. Yamanaka and his colleagues established induced pluripotent stem cells (iPSCs) which could be generated from somatic cells, and this innovative development has made rapid progression in the field of SCI regeneration. We and other groups succeeded in producing NPCs from iPSCs, and demonstrated beneficial effects after transplantation for animal models of SCI. In particular, efficacy of human iPSC-NPCs in non-human primate SCI models fostered momentum of clinical application for SCI patients. At the same time, however, artificial induction methods in iPSC technology created alternative issues including genetic and epigenetic abnormalities, and tumorigenicity after transplantation. To overcome these problems, it is critically important to select origins of somatic cells, use integration-free system during transfection of reprogramming factors, and thoroughly investigate the characteristics of iPSC NPCs with respect to quality management. Moreover, since most of the previous studies have focused on subacute phase of SCI, establishment of effective NPC transplantation should be evaluated for chronic phase hereafter. Our group is currently preparing clinical-grade human iPSC-NPCs, and will move forward toward clinical study for subacute SCI patients soon in the near future. PMID- 28993836 TI - Natural (and Unnatural) Small Molecules as Pharmacological Chaperones and Inhibitors in Cancer. AB - Mutations causing single amino acid exchanges can dramatically affect protein stability and function, leading to disease. In this chapter, we will focus on several representative cases in which such mutations affect protein stability and function leading to cancer. Mutations in BRAF and p53 have been extensively characterized as paradigms of loss-of-function/gain-of-function mechanisms found in a remarkably large fraction of tumours. Loss of RB1 is strongly associated with cancer progression, although the molecular mechanisms by which missense mutations affect protein function and stability are not well known. Polymorphisms in NQO1 represent a remarkable example of the relationships between intracellular destabilization and inactivation due to dynamic alterations in protein ensembles leading to loss of function. We will review the function of these proteins and their dysfunction in cancer and then describe in some detail the effects of the most relevant cancer-associated single amino exchanges using a translational perspective, from the viewpoints of molecular genetics and pathology, protein biochemistry and biophysics, structural, and cell biology. This will allow us to introduce several representative examples of natural and synthetic small molecules applied and developed to overcome functional, stability, and regulatory alterations due to cancer-associated amino acid exchanges, which hold the promise for using them as potential pharmacological cancer therapies. PMID- 28993837 TI - GABA Receptors and the Pharmacology of Sleep. AB - Current GABAergic sleep-promoting medications were developed pragmatically, without making use of the immense diversity of GABAA receptors. Pharmacogenetic experiments are leading to an understanding of the circuit mechanisms in the hypothalamus by which zolpidem and similar compounds induce sleep at alpha2betagamma2-type GABAA receptors. Drugs acting at more selective receptor types, for example, at receptors containing the alpha2 and/or alpha3 subunits expressed in hypothalamic and brain stem areas, could in principle be useful as hypnotics/anxiolytics. A highly promising sleep-promoting drug, gaboxadol, which activates alphabetadelta-type receptors failed in clinical trials. Thus, for the time being, drugs such as zolpidem, which work as positive allosteric modulators at GABAA receptors, continue to be some of the most effective compounds to treat primary insomnia. PMID- 28993838 TI - Delta Opioid Receptor Expression and Function in Primary Afferent Somatosensory Neurons. AB - The functional diversity of primary afferent neurons of the dorsal root ganglia (DRG) generates a variety of qualitatively and quantitatively distinct somatosensory experiences, from shooting pain to pleasant touch. In recent years, the identification of dozens of genetic markers specifically expressed by subpopulations of DRG neurons has dramatically improved our understanding of this diversity and provided the tools to manipulate their activity and uncover their molecular identity and function. Opioid receptors have long been known to be expressed by discrete populations of DRG neurons, in which they regulate cell excitability and neurotransmitter release. We review recent insights into the identity of the DRG neurons that express the delta opioid receptor (DOR) and the ion channel mechanisms that DOR engages in these cells to regulate sensory input. We highlight recent findings derived from DORGFP reporter mice and from in situ hybridization and RNA sequencing studies in wild-type mice that revealed DOR presence in cutaneous mechanosensory afferents eliciting touch and implicated in tactile allodynia. Mechanistically, we describe how DOR modulates opening of voltage-gated calcium channels (VGCCs) to control glutamatergic neurotransmission between somatosensory neurons and postsynaptic neurons in the spinal cord dorsal horn. We additionally discuss other potential signaling mechanisms, including those involving potassium channels, which DOR may engage to fine tune somatosensation. We conclude by discussing how this knowledge may explain the analgesic properties of DOR agonists against mechanical pain and uncovers an unanticipated specialized function for DOR in cutaneous mechanosensation. PMID- 28993839 TI - Predicting suitability of intramedullary fixation for displaced midshaft clavicle fractures. AB - PURPOSE: Implant-related irritation is a technique-specific complication seen in a substantial number of patients treated with intramedullary nailing for clavicle fractures. The purpose of this study was to identify predictors for developing implant-related irritation in patients with displaced midshaft clavicle fractures treated with elastic stable intramedullary nailing. METHODS: A retrospective analysis of the surgical database in two level 2 trauma centers was performed. Patients who underwent intramedullary nailing for displaced midshaft clavicle fractures between 2005 and 2012 in the first hospital were included. Age, gender, fracture comminution and fracture location were assessed as possible predictors for developing irritation using multivariate logistic regression analysis. These predictors were externally validated using data of patients treated in another hospital. RESULTS: Eighty-one patients were included in initial analysis. In the multivariate analysis, comminuted fractures in comparison to non-comminuted fractures (72 vs. 38%, p = 0.027) and fracture location (p < 0.001) were significantly associated with the development of implant-related irritation. In particular, lateral diaphyseal fractures caused irritation compared to fractures on the medial side of the cut-off point (88 vs. 26%). External validation of these predictors in 48 additional patients treated in another hospital showed a similar predictive value of the model and a good fit. CONCLUSION: Comminuted and lateral diaphyseal fractures were found to be statistically significant and independent predictors for developing implant-related irritation. We, therefore, believe that intramedullary nailing might not be suitable for these types of fractures. Future studies are needed to determine whether alternative surgical techniques or implants would be more suitable for these specific types of fractures. PMID- 28993840 TI - Impact of right ventricular diastolic dysfunction on clinical outcomes in inferior STEMI. AB - BACKGROUND: The aim of this study was to investigate the prognostic value of restrictive right ventricular filling pattern (RRVFP) in patients with the first acute inferior wall myocardial infarction (IWMI) complicated by right ventricular myocardial infarction (RVMI) undergoing primary percutaneous coronary intervention (p-PCI). METHOD: A total of 152 patients with acute IWMI complicated by RVMI undergoing p-PCI were divided into two groups according to the presence of RRVFP. RRVFP was defined as tricuspid diastolic early/late flow velocities (Et/At) > 2 and Et deceleration time (DT) < 120 ms. RESULTS: There were 23 patients with RRVFP in the study cohort. At, DTt, isovolumetric relaxation time (IVRT), and tissue Doppler tricuspid annular late velocity (A't) were reduced significantly in patients with RRVFP than in those without RRVFP (At 19.6 +/- 2.7 vs. 39.1 +/- 7.4 cm/s, p < 0.001; DTt 106 +/- 13 vs.156 +/- 21 ms, p = 0.001; IVRT 59 +/- 6.7 vs. 62 +/- 7.4 ms, p = 0.01; A't 4.6 +/- 1.1 vs. 8.6 +/- 1.05, p = 0.001). Et/At ratios were higher in patients with RRVFP than in those without RRVFP (Et/At 2.20 +/- 0.2 vs. 1.15 +/- 0.37, p < 0.001). Et, tissue Doppler tricuspid annular early velocity (E't), E't/A't ratio, and Et/E't ratio were not significantly different between groups (Et 43.3 +/- 5.4 vs. 40.7 +/- 9.2 cm/s p = 0.18; E't 8.8 +/- 1.4 vs. 9.5 +/- 2.3, p = 0.15; E't/A't 1.08 +/- 0.24 vs. 1.13 +/- 0.30, p = 0.52; Et/E't ratio 5.0 +/- 1.1 vs. 4.5 +/- 1.5 p = 0.09). Presence of E't/A't > 2, short DTt, RRVFP, unsuccessful p-PCI, and cardiogenic shock on admission were independent predictors of in-hospital mortality (p < 0.05) in multivariable logistic regression analysis. CONCLUSION: Presence of RRVFP is associated with in-hospital mortality in patients presenting with their first IWMI complicated by RVMI. PMID- 28993841 TI - Extent of jugular venous distension and lower extremity edema are the best tools from history and physical examination to identify heart failure exacerbation. AB - INTRODUCTION: We aimed to identify the best tools from history and physical examination that predict severity of heart failure (HF) exacerbation among patients with an ejection fraction (EF) <= 30%. METHODS: Patients enrolled in the ESCAPE trial were divided into tertiles according to the combined value of pulmonary capillary wedge pressure (PCWP) and right atrial pressure (RAP) which we used as a marker of volume loading of both pulmonary and systemic compartments. Variables of congestion from history and physical examination were examined across tertiles. RESULTS: There were significant differences across tertiles (tertile 1: PCWP + RAP < 31 mm Hg, tertile 2: PCWP + RAP 31-42 mm Hg and tertile 3: PCWP + RAP > 42 mm Hg) with respect to baseline B-type natriuretic peptide (P = 0.016), blood urea nitrogen (P = 0.022), sodium (P = 0.015), left ventricular ejection fraction (P = 0.005), and inferior vena cava diameter during inspiration (P < 0.001) and expiration (P < 0.001). With respect to variables of congestion from history and physical examination, we found significant differences across tertiles predominantly in signs of right sided failure, specifically, the frequency of jugular venous distension (JVD, P < 0.001) and JVD > 12 cmH2O (p < 0.001), lower extremity edema (P = 0.001) and lower extremity edema of at least grade 2 + (P = 0.029), and positive hepatojugular reflux (HJR, P = 0.022) but no differences in patients' symptoms such as degree of dyspnea, orthopnea or fatigue. With regards to post-discharge outcomes, there was a significant difference across tertiles in all-cause mortality (P = 0.029) and rehospitalization for HF (P = 0.031) at 6 months following randomization. Receiver operator characteristic curves showed that admission PCWP + RAP had an area under the curve of 0.623 (P = 0.0075) and 0.617 (P = 0.0048), respectively, in predicting 6-month all-cause mortality and rehospitalization for HF. CONCLUSION: The presence and extent of JVD and lower extremity edema, and a positive HJR are better than other signs and symptoms in identifying severity of HF exacerbation among patients with EF <= 30%. PMID- 28993842 TI - [The right opioid for my patient]. PMID- 28993843 TI - In-hospital mortality after acute STEMI in patients undergoing primary PCI. AB - BACKGROUND: Acute myocardial infarction (AMI) is the main cause of global and in hospital mortality in patients with cardiovascular diseases. We aimed to examine the association between the coronary artery involved and the in-hospital mortality in patients who underwent primary percutaneous coronary intervention (pPCI) after ST segment elevation myocardial infarction (STEMI). METHODS: The in hospital mortality of STEMI patients who underwent pPCI was assessed at the Department of Cardiology, Harzklinik Goslar, Germany, which has no access to immediate mechanical circulatory support (MCS), between 2013 and 2017. RESULTS: We enrolled 312 STEMI patients, with a mean age of 67.1 +/- 13.4 years, of whom 211 (68%) were male. In-hospital mortality was documented in 31 patients (10%). In-hospital mortality was associated with pre-hospital cardiopulmonary resuscitation (CPR; n = 39/12.5%), older age, lower systolic blood pressure, Killip class > 1, triple-vessel disease (each p < 0.0001), female gender (p = 0.0158), and with the localization of the treated culprit lesion in the left main coronary artery (LMCA; p = 0.0083) and in the ramus circumflexus (RCX; p = 0.0141). CONCLUSION: In this monocentric cohort, all-cause in-hospital mortality of STEMI patients after pPCI was significantly higher in those patients with culprit lesions in the LMCA and in the RCX, which may prove to be a substantial novel risk factor for STEMI-related mortality. Increasing age and female gender may be interdependent risk factors for mortality in this patient population. Furthermore, our data highlight the importance of the availability of MCS options in pPCI centers for patients after CPR. PMID- 28993844 TI - Lost and found: the science lost in World War II. PMID- 28993845 TI - [New experimental strategies in cartilage surgery]. AB - BACKGROUND: Cell and growth factor based strategies bear great potential to support the healing processes in cartilage repair and the therapy of osteoarthritic joints. OBJECTIVES: The following review provides an overview of novel experimental strategies for the therapy of focal cartilage defects and osteoarthritis, with emphasis on cell and growth factor based approaches. MATERIALS AND METHODS: The authors summarize their own data regarding the intraarticular injection of stem cells to treat osteoarthritis of the knee and provide a synopsis of the available literature discussing the most significant publications. RESULTS: The development of novel strategies for the treatment of focal and arthrotic cartilage lesions focuses on the application of growth factors, platelet rich plasma (PRP), bone marrow (BMSAC) or adipose derived (stromal vascular fraction - SVF) cell concentrates, and ex vivo expanded mesenchymal stem cells (MSC). First clinical data on the use of expanded MSCs show the potential of this innovative therapeutic strategy. These approaches, however, are governed by EU law and often require approval by regulatory bodies. CONCLUSION: Currently, only a limited number of published, randomized, controlled trials available. Therefore, it is not possible to finally assess the efficacy of these strategies at this point in time. PMID- 28993846 TI - [Hyaluronan as a key for accelerated wound healing in human 3D full thickness skin models]. AB - BACKGROUND: Wound healing can be divided into three phases: (1) exsudation phase, (2) granulation phase, (3) regeneration phase. In particular, the epithelization phase is of great importance in order to quickly reconstitute the natural skin barrier. The aim of the present study was to determine the reepithelization kinetics of untreated and 0.5% sodium hyaluronate (NHA) treated human 3D full thickness skin models. MATERIALS AND METHODS: The test protocol consisted of topically applying 10 ul of the test substance 0.5% NHA twice a day. Evaluation of reepithelialization kinetics was carried out from days 2-6. Determination of the influence on immune response was performed based on quantification of IL 1alpha and IL-10. RESULTS: Application of 0.5% NHA twice a day enhanced the reepithelialization speed at all time points (p < 0.001). This observation is accompanied by a reduced expression of IL-10 paralleled by an elevated expression of IL-1alpha on days 2-4 (p < 0.001). DISCUSSION: The treatment of human skin models with NHA resulted in a significantly increased reepithelization velocity of wounded tissue and consequently promoted faster wound closure, compared to untreated controls. It can be assumed that the downregulation of IL-10 caused the IL1-alpha mediated increased immune response which finally leads to accelerated wound healing. Follow-up studies will reveal if the faster wound healing and the modulation of the immune response through the application of NHA is valid in vivo. PMID- 28993847 TI - Vitamin D deficiency and functional response to CRT in heart failure patients. AB - BACKGROUND: Vitamin D deficiency has been associated with a poor outcome in patients with heart failure (HF). We examined the role of vitamin D in the response of HF patients to cardiac resynchronization therapy (CRT). METHODS: The study comprised 50 patients (30 men and 20 women) with HF undergoing CRT implantation who were prospectively enrolled. Response to CRT was defined as a combination of >=15% reduction in left ventricular end-systolic volume (LVESV) and >=10% improvement in the 6-Minute Walk Test within 6 months. Patients were grouped based on their levels of vitamin D prior to CRT implantation. Clinical and echocardiographic examinations were performed prior to and 6 months after the procedure. RESULTS: Of the patients, 11 (22%) failed to respond to CRT; two patients died within 6 months and an additional nine patients showed no improvement in the 6-Minute Walk Test and no reduction in their baseline LVESV. A comparison was made between 25 patients with sufficient levels of vitamin D and 25 patients with insufficient levels. Nine patients (36%) in the "insufficient" group and two patients (8%) in the "sufficient" group failed to respond to CRT implantation (p = 0.037). CONCLUSION: Adequate serum concentrations of vitamin D play a significant role in improving the functional status of patients with systolic HF following CRT implantation. PMID- 28993848 TI - Altered long-term health-related quality of life in patients following patella fractures: a long-term follow-up study of 49 patients. AB - INTRODUCTION: The primary aim was to investigate the health-related quality of life (HRQOL) in patients treated for a patella fracture. The explorative aim was to report the associations between HRQOL, knee osteoarthritis, muscle strength and gait function. METHODS: The study design was a cohort study. Patients who were treated for patella fractures at Aalborg University Hospital, Denmark between January 2006 and December 2009 were identified. Patients between the age of 18 and 80 were included. The main outcome was assessed by the EQ5D-5L questionnaire. Classifications by Sperner and Kellgren/Lawrence were applied to evaluate osteoarthritis. Moreover, functional outcomes were evaluated by: KOOS, muscle strength and gait analysis. RESULTS: Forty-nine patients were included with a mean follow-up time of 8.5 years. The mean age was 53.9 years. The mean EQ5D-5L index value was 0.741, and was significantly worse compared to a reference population. X-rays taken at the time of diagnosis and the time of follow-up showed progression towards a higher degree of osteoarthritis in the injured knee for both the patellofemoral and tibiofemoral joints. Patients demonstrated significantly lower knee extension strength in the injured leg compared to the non-injured leg (P = 0.011). No significant difference in gait speed and cadence were observed compared to the reference population. Knee osteoarthritis, muscle strength and gait patterns were not associated with HRQOL (R < 0.35). CONCLUSION: At 8.5 years following a patella fracture, HRQOL was significantly worse compared to an age-matched reference population. PMID- 28993849 TI - Identification of Novel Congenital Heart Disease Candidate Genes Using Chromosome Microarray. AB - While the majority of patients have isolated heart disease, congenital heart disease (CHD) may be associated with other congenital anomalies or syndromes. Our institution utilizes chromosomal microarray (CMA) to identify chromosomal abnormalities, specifically copy number variations (CNVs). While CNVs have been associated with CHD, their direct impact on cardiac development remains unclear. This study sought to identify potential novel CHD candidate genes by comparing CNVs present in our institution's CHD population with those already recognized in the literature. A list of candidate genes was compiled from recent medical literature that utilized CMA. Records from neonatal cases at our institution over 10 years were reviewed. Genes identified from CMAs were compared with those reported in the literature and cross-referenced with the Online Mendelian Inheritance in Man catalog. We identified 375 CNVs reported in patients with CHD. At our institution between 2005 and 2015, 307 neonates with CHD had CMA. Of these, 77 patients (25%) had CNVs containing 832 unique candidate genes. 49 patients (16%) had isolated CHD with 353 candidate genes expressed within the CNVs, many of which were previously reported. However, there were 16 unique candidate genes identified that have been expressed with heart structure of the mouse knock-out models. Our findings demonstrate a high incidence of abnormal genes identified by CMA in CHD patients, including many CNVs of "unknown clinical significance". We conclude that a portion of these CNVs (including 16 genes expressed in the heart of the mouse knock-out models) could be candidate genes involved in CHD pathogenesis. PMID- 28993850 TI - Expression of Collagenase is Regulated by the VarS/VarA Two-Component Regulatory System in Vibrio alginolyticus. AB - Vibrio alginolyticus is an opportunistic pathogen in both humans and marine animals. Collagenase encoded by colA is considered to be one of the virulence factors. Expression of colA is regulated by multiple environmental factors, e.g., temperature, growth phase, and substrate. To elucidate the mechanism of regulation of colA expression, transposon mutagenesis was performed. VarS, a sensor histidine kinase of the two-component regulatory system, was demonstrated to regulate the expression of colA. VarA, a cognate response regulator of VarS, was also identified and shown to be involved in the regulation of colA expression. In vitro phosphorylation assays showed that phosphorylated VarS acted as a phosphoryl group donor to VarA. A site-directed mutagenesis study showed that the His300, Asp718 and His874 residues in VarS were essential for the phosphorylation of VarS, and the Asp54 residue in VarA was likely to receive the phosphoryl group from VarS. The results demonstrate that the VarS/VarA two component regulatory system regulates the expression of collagenase in V. alginolyticus. PMID- 28993851 TI - Usefulness of the WCD in patients with suspected tachymyopathy. AB - AIMS: The wearable cardioverter defibrillator (WCD) is used for temporary protection of patients deemed to be at high risk for sudden death. There is limited experience regarding the clinical development of patients with tachymyopathy. We aimed to evaluate the clinical development of tachymyopathy patients protected with a WCD in a single-center non-randomized patient cohort. METHODS AND RESULTS: We fitted 130 consecutive patients deemed to be at high risk for ventricular tachyarrhythmias with the WCD. Of these, 20 patients (15%) presenting with newly diagnosed heart failure in the setting of rapidly conducted atrial fibrillation/flutter were suspected to suffer from tachymyopathy. The control group consisted of the remaining 110 patients with other indications for WCD therapy. LVEF increased by more than 10% in 13/20 (65%) tachymyopathy patients compared to 40/110 (36%) patients in the control population (p = 0.01). Similarly, BNP levels decreased in 15/20 (75%) tachymyopathy patients compared to 41/110 (37%) in the control group (p = 0.05). ICD implantation rates were lower in the tachymyopathy group (3/20) compared to the control population (40/110; p = 0.04). On further follow-up (mean 12 +/- 8 months), patients with suspected tachymyopathy had no sustained ventricular arrhythmias. Compared to 5/110 patients in the control group, no tachymyopathy patient died. CONCLUSION: Most of the patients with suspected tachymyopathy have a favorable clinical outcome. The WCD is useful for temporary protection while LV function recovers. PMID- 28993852 TI - The effects of the obesogen tributyltin on the metabolism of Sertoli cells cultured ex vivo. AB - Human exposure to environmental contaminants is widespread. Some of these contaminants have the ability to interfere with adipogenesis, being thus considered as obesogens. Recently, obesogens have been singled out as a cause of male infertility. Sertoli cells (SCs) are essential for male fertility and their metabolic performance, especially glucose metabolism, is under a tight endocrine control, being essential for the success of spermatogenesis. Herein, we studied the impact of the model obesogen tributyltin in the metabolic profile of SCs. For that, ex vivo-cultured rat SCs were exposed to increasing doses of tributyltin. SCs proliferation was evaluated by the sulforhodamine B assay and the maturation state of the cells was assessed by the expression of specific markers (inhibin B and the androgen receptor) by quantitative polymerase chain reaction. The metabolic profile of SCs was established by studying metabolites consumption/production by nuclear magnetic resonance spectroscopy and by analyzing the expression of key transporters and enzymes involved in glycolysis by Western blot. The proliferation of SCs was only affected in the cells exposed to the highest dose (1000 nM) of tributyltin. Notably, SCs exposed to 10 nM tributyltin decreased the consumption of glucose and pyruvate, as well as the production of lactate. The decreased lactate production hampers the development of germ cells. Intriguingly, the lowest levels of tributyltin were more prone to modulate the expression of key players of the glycolytic pathway. This is the first study showing that tributyltin reprograms glucose metabolism of SCs under ex vivo conditions, suggesting new targets and mechanisms through which obesogens modulate the metabolism of SCs and thus male (in)fertility. PMID- 28993853 TI - Analysis of Medium-Chain-Length Polyhydroxyalkanoate-Producing Bacteria in Activated Sludge Samples Enriched by Aerobic Periodic Feeding. AB - Analysis of mixed microbial populations responsible for the production of medium chain-length polyhydroxyalkanoates (MCL-PHAs) under periodic substrate feeding in a sequencing batch reactor (SBR) was conducted. Regardless of activated sludge samples and the different MCL alkanoic acids used as the sole external carbon substrate, denaturing gradient gel electrophoresis analysis indicated that Pseudomonas aeruginosa was the dominant bacterium enriched during the SBR process. Several P. aeruginosa strains were isolated from the enriched activated sludge samples. The isolates were subdivided into two groups, one that produced only MCL-PHAs and another that produced both MCL- and short-chain-length PHAs. The SBR periodic feeding experiments with five representative MCL-PHA-producing Pseudomonas species revealed that P. aeruginosa has an advantage over other species that enables it to become dominant in the bacterial community. PMID- 28993854 TI - [Autophagy in the genesis of pancreatic ductal adenocarcinoma]. PMID- 28993855 TI - Postoperative fixed flexion deformity greater than 10 degrees lead to poorer functional outcome 10 years after unicompartmental knee arthroplasty. AB - PURPOSE: The primary aim of this study was to evaluate the influence of postoperative fixed flexion deformity (FFD) on the clinical outcomes 10 years after unicompartmental knee arthroplasty (UKA). The secondary aim was to identify predictors for the occurrence of postoperative FFD. METHODS: Patients who underwent UKA between 2003 and 2007 were prospectively followed up for 10 years. A total of 172 patients were categorized into 3 groups based on the amount of postoperative FFD: (1) 0 degrees or less (Min-FFD), (2) 1 degrees -9 degrees (Mid-FFD), and (3) 10 degrees or more (Max-FFD). Functional outcome was quantified using Knee Society Function Score (KSFS), Knee Society Knee Score (KSKS) and Oxford Knee Score (OKS). RESULTS: At 10 years after UKA, the mean KSKS and OKS were 6 +/- 5 (95% CI 6-18, p = 0.050) and 5 +/- 2 (95% CI 0-9, p = 0.041) points lower in patients with Max-FFD than those with Min-FFD. Other clinical outcomes were not different between groups. Patients with a higher preoperative body mass index (OR 1.122 per unit increase, 95% CI 1.006-1.253, p = 0.040) or worse preoperative FFD (OR 1.108 per unit increase, 95% CI 1.022-1.201, p = 0.013) were at increased risk of having postoperative FFD of 10 degrees or more at 10 years after UKA. CONCLUSIONS: The clinical relevance of this study was to demonstrate the long-term negative correlation between severe postoperative FFD and functional outcome and, therefore, the importance of achieving good knee alignment after UKA. The authors recommend that FFD should be fully corrected intra-operatively if possible while preserving knee balance and stable dynamic function through full range of motion. LEVEL OF EVIDENCE: Prognostic level II. PMID- 28993856 TI - [Malignant lymphomas of the eye]. AB - The eye and the ocular adnexae are rare sites for malignant non-Hodgkin lymphoma (NHL). Based on their anatomical location, intraocular lymphomas must be discerned from NHL of adnexal structures including conjunctiva, lacrimal gland, and orbit. Whereas the latter group mostly consists of indolent extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) type or secondary manifestations of systemic NHL, most primary intraocular lymphomas are classified as diffuse large B-cell lymphomas (DLBCL) and are considered a variant of primary DLBCL of the central nervous system. The most common form is primary vitreoretinal lymphoma (PVRL), which presents with nonspecific symptoms and is difficult to discern from uveitis. Diagnosis of PVRL is usually made by cytological, immunocytochemical, and molecular analysis of vitreous aspirates. Degenerative changes, limited material, and the occurrence of pseudoclonality in the molecular analysis of B-cell clonality can hamper diagnostic assessment. Novel techniques such as detection of MYD88 mutations common in PVRL can increase diagnostic sensitivity. Close cooperation with clinical colleagues and rapid specimen processing are fundamental for successful diagnosis. PMID- 28993857 TI - SMABcare study: subcutaneous monoclonal antibody in cancer care: cost-consequence analysis of subcutaneous rituximab in patients with follicular lymphoma. AB - Rituximab is used as a standard of care for follicular lymphoma and is usually administered intravenously. A novel subcutaneous formulation recently showed non inferior efficacy with similar pharmacokinetic and safety profiles compared to intravenous rituximab in patients with follicular lymphoma. This new approach is promising in terms of comfort for patients and time-saving for hospital staff. To evaluate the real-life economic impact of subcutaneous rituximab as maintenance therapy in patients with follicular lymphoma in real life, we conducted a cost consequence analysis from the hospital's point of view in three French teaching hospitals. Health-related quality of life (EQ-5D-3L) was investigated as well as patients' and nurses' perception. Compared to intravenous rituximab, subcutaneous administration showed an estimated cost-saving of ?109.20 per patient per cycle (p < 0.001), 78.6% of which could be attributed to the rituximab cost. Health related quality of life showed no significant difference between the two groups despite tendencies for greater pain in the subcutaneous group and greater anxiety in the intravenous group. Thus, subcutaneous rituximab had a favorable pharmacoeconomic profile, with clinical efficacy similar to that of intravenous rituximab. The subcutaneous form was preferred by almost all patients, but further consideration should be given to improve the patients' experience: a dedicated day unit with trained medical, nursing, and pharmaceutical staff could be helpful. PMID- 28993858 TI - Treatment of abdominal pseudocysts and associated ventricuoperitoneal shunt failure. AB - PURPOSE: The purpose of this study was to determine whether drainage and revision are an effective treatment for abdominal pseudocyst associated ventriculoperitoneal (VP) shunt failure by estimating the total rate of secondary shunt failure. METHODS: We performed a retrospective review of children with hydrocephalus diagnosed with and treated for an abdominal pseudocyst at the Children's Hospital, London Health Sciences Centre (LHSC) between January 1, 2000 and May 31, 2016 (ethics approval # 108136). Patients with a VP shunt were included if (i) the development of an abdominal pseudocyst at age 2 to 18 years was identified, (ii) treatment of the pseudocyst by either interventional radiology (IR) or surgical drainage, and (iii) revision of the VP shunt. Demographic data and details of pseudocyst formation/ treatment as well as subsequent failures were identified. RESULTS: Twelve patients who had a VP shunt developed abdominal pseudocyst and met inclusion criteria. A 91% shunt failure rate after drainage and shunt revision was identified. Three patients had the pseudocyst drained in interventional radiology and then externalized due to shunt infection. Nine patients were treated by surgical revision. Ten patients experienced recurrent shunt failure following initial drainage of the pseudocyst: pseudocyst reoccurrence (n = 3), distal obstruction from adhesions (n = 1), and uncleared infection (n = 6). CONCLUSION: The results suggest that pseudocyst drainage and shunt revision is ineffective in providing long-term resolution of shunt problems. PMID- 28993859 TI - [Diabetes mellitus]. PMID- 28993861 TI - [Intraocular metastases]. AB - Metastatic cancer represents the most common form of intraocular malignancy. Due to its abundant vascular supply the choroid is the most common ocular site for intraocular metastatic disease (approximately 90%). Less than 10% of intraocular metastases are located in the iris and/or ciliary body, whereas the retina and vitreous are rarely affected. Most intraocular metastases are carcinomas; the majority of metastases originate from breast cancer in females and lung cancer in males. However, virtually every primary malignancy has been described to metastasize to intraocular structures. In this review we address the pathology and clinical features of intraocular metastases, noninvasive and invasive diagnostic procedures, as well as the pathological work-up of cytological and histological specimens obtained either by fine needle aspiration biopsy or special biopsy forceps. PMID- 28993860 TI - Lanthanum damages learning and memory and suppresses astrocyte-neuron lactate shuttle in rat hippocampus. AB - Rare-earth elements (REEs) are applied in various fields by virtue of their superior physical and chemical properties. Surveys have reported that REEs can impair learning and memory in children and induce neurobehavioral abnormalities in animals. However, the mechanism underlying this neurotoxicity is still unclear. Lanthanum (La) is often chosen to study the effects of REEs. Here, we investigated the role of astrocyte-neuron lactate shuttle (ANLS) in spatial learning and memory impairment induced by LaCl3 in hippocampus, an important spatial memory-related brain region. Pregnant Wistar rats were exposed to 0, 0.125, 0.25, 0.5, or 1% LaCl3 in drinking water during pregnancy and lactation. After weaning, young rats continued to receive 0, 0.125, 0.25, 0.5, and 1% LaCl3 in the drinking water for 1 month. The results showed that LaCl3 exposure impaired the spatial learning and memory of rats in Morris water maze test, significantly reduced the mRNA and protein levels of glycogen synthetase, glycogen phosphorylase, lactate dehydrogenase A, monocarboxylate transporter 4, MCT-1, and MCT-2, and decreased total LDH activity and lactate contents in rat hippocampus. These results indicate that LaCl3 impairs spatial learning and memory in rats probably by suppressing ANLS in rat hippocampus. The study provides a novel clue of energy supply for neurons to clarify the neurotoxicity of REEs. PMID- 28993863 TI - Long-term Water Table Monitoring of Rio Grande Riparian Ecosystems for Restoration Potential Amid Hydroclimatic Challenges. AB - Hydrological processes drive the ecological functioning and sustainability of cottonwood-dominated riparian ecosystems in the arid southwestern USA. Snowmelt runoff elevates groundwater levels and inundates floodplains, which promotes cottonwood germination. Once established, these phreatophytes rely on accessible water tables (WTs). In New Mexico's Middle Rio Grande corridor diminished flooding and deepening WTs threaten native riparian communities. We monitored surface flows and riparian WTs for up to 14 years, which revealed that WTs and surface flows, including peak snowmelt discharge, respond to basin climate conditions and resource management. WT hydrographs influence the composition of riparian communities and can be used to assess if potential restoration sites meet native vegetation tolerances for WT depths, rates of recession, and variability throughout their life stages. WTs were highly variable in some sites, which can preclude native vegetation less adapted to deep drawdowns during extended droughts. Rates of WT recession varied between sites and should be assessed in regard to recruitment potential. Locations with relatively shallow WTs and limited variability are likely to be more viable for successful restoration. Suitable sites have diminished greatly as the once meandering Rio Grande has been constrained and depleted. Increasing demands on water and the presence of invasive vegetation better adapted to the altered hydrologic regime further impact native riparian communities. Long-term monitoring over a range of sites and hydroclimatic extremes reveals attributes that can be evaluated for restoration potential. PMID- 28993864 TI - Frequency sensitivity in Northern saw-whet owls (Aegolius acadicus). AB - Northern saw-whet owls (Aegolius acadicus) are known for their unique asymmetrical ear structure and ability to localize prey acoustically, yet few attempts have been made to explore the auditory capabilities of this species. In this study, we evoked auditory brainstem responses (ABRs) with tonebursts to assess three main hypotheses regarding the evolution of auditory sensitivity: sender-receiver matching, ecological constraints, and phylogenetic/morphological constraints. We found that ABR amplitude increased with increasing stimulus level, which is consistent with results in other avian species. ABR amplitudes, latencies, and thresholds indicate that the hearing range of Northern saw-whet owls extends from 0.7 to 8.6 kHz, with an extended frequency range of best sensitivity between 1.6 and 7.1 kHz. Sensitivity fell off rapidly above and below these frequencies. The average audiogram was structurally similar to those found in other species of owls, suggesting that phylogeny or morphology may be constraining the frequency range of auditory sensitivity. However, ABR thresholds were 10-25 dB lower than those of Eastern screech-owls (Megascops asio), with thresholds below 0 dB SPL in some individuals. The lowest thresholds were at frequencies not found in the vocalizations of Northern saw-whet owls, suggesting ecological constraints rather than conspecific vocalizations are driving absolute sensitivity. PMID- 28993862 TI - Utilization of bone mineral density testing among breast cancer survivors in British Columbia, Canada. AB - : Breast cancer survivors are at high osteoporosis risk. Bone mineral density testing plays a key role in osteoporosis management. We analyzed a historical utilization of bone mineral density testing in breast cancer survivors. The utilization remained low in the 1995-2008 period. Lower socio-economic status and rural residency were associated with lower utilization. INTRODUCTION: To evaluate the utilization of bone mineral density (BMD) testing for female breast cancer survivors aged 65+ surviving >= 3 years in British Columbia, Canada. METHODS: A retrospecitve population-based data linkage study. Trends in proportion of survivors with >= 1 BMD test for each calendar year from 1995 to 2008 were evaluated with a serial cross-sectional analysis. Associations between factors (socio-demographic and clinical) and BMD testing rates over the period 2006-2008 for 7625 survivors were evaluated with a cross-sectional analysis and estimated as adjusted prevalence ratios (PRadj) using log-binomial models. RESULTS: Proportions of survivors with >= 1 BMD test increased from 1.0% in 1995 to 10.1% in 2008. The BMD testing rate in 2006-2008 was 26.5%. Socio-economic status (SES) and urban/rural residence were associated with BMD testing rates in a dose dependent relationship (p for trend< 0.01). Survivors with lower SES (PRadj = 0.66-0.78) or rural residence (PRadj = 0.70) were 20-30% less likely to have BMD tests, compared with survivors with the highest SES or urban residence. BMD testing rates were also negatively associated with older age (75+) (PRadj = 0.47; 95% CI = 0.42, 0.52), nursing home residency (0.05; 0.01, 0.39), recent osteoporotic fractures (0.21; 0.14, 0.32), and no previous BMD tests (0.26; 0.23, 0.29). CONCLUSION: Utilization of BMD testing was low for breast cancer survivors in BC, Canada. Lower SES and rural residence were associated with lower BMD testing rates. IMPLICATION FOR CANCER SURVIVORS: Female breast cancer survivors, especially those with lower SES or rural residence, should be encouraged to receive BMD tests as recommended by Canadian guidelines. PMID- 28993866 TI - CDH1 mutation screen in a BRCA1/2-negative familial breast-/ovarian cancer cohort. AB - PURPOSE: Mutations in the CDH1 gene are linked both to diffuse gastric cancer and invasive lobular carcinoma (ILC). A high mutation rate is found in families fulfilling the diagnostic criteria for hereditary diffuse gastric cancer. Aim of this study was to clarify whether or not there is a significant contribution of CDH1 mutations in hereditary breast-/ovarian cancer (HBOC). METHODS: Ninety-seven unrelated probands fulfilling the diagnostic criteria for HBOC (96 affected, 1 unaffected) but tested negative for pathogenic BRCA1/2 mutations were screened for CDH1 mutations by denaturing high performance liquid chromatography (DHPLC) and subsequent Sanger sequencing of suspicious and positive DHPLC results. RESULTS: In total, we found two potentially pathogenic CDH1 alterations, c.1774G > A, pAla592Thr, and c.2512 A > G, p.Ser838Gly, classified as variants of unknown significance according to ClinVar. In addition, we detected a high number of known CDH1 polymorphisms (n = 62), some of them more frequent in patients with lobular (55%) than in those with invasive ductal carcinoma (27%). CONCLUSION: Although none of the probands studied carried a clearly pathogenic CDH1 mutation, CDH1 could be considered a potential breast cancer gene, esp. for ILC worth including it in the NGS (next generation sequencing) HBOC panel. PMID- 28993865 TI - Two-year cortical and trabecular bone loss in CKD-5D: biochemical and clinical predictors. AB - : This prospective two-year study of patients on chronic dialysis measured changes in bone mineral density (BMD). Patients with higher baseline BMD and shorter dialysis vintage lost more bone. Treatment with anti-hypertensives acting on the central nervous system was protective against bone loss. Baseline serum levels of sclerostin and bone-specific alkaline phosphatase predicted bone loss. INTRODUCTION: This prospective 2-year study of chronic kidney disease on dialysis (CKD-5D) patients assessed trabecular and cortical bone loss at the hip and spine and examined potential demographic, clinical, and serum biochemical predictors of bone loss. METHODS: Eighty-nine CKD-5D patients had baseline, year 1, and year 2 bone mineral density (BMD) measurements using dual X-ray absorptiometry (DXA) and quantitative computed tomography (QCT); concurrent blood samples were drawn and clinical variables recorded. No study treatments occurred. RESULTS: The 2-year total hip BMD change was - 5.9% by QCT and - 3.1% by DXA (p < 0.001). Spinal BMD was unchanged. QCT total hip cortical mass and volume decreased (- 7.3 and - 10.0%); trabecular volume increased by 5.9% (ps < 0.001). BMD changes did not vary with age, BMI, race, diabetes, smoking, or exercise. Patients with higher baseline BMD and shorter dialysis vintage lost more bone (p < 0.05). Vitamin D analogs and phosphate binders were not protective against bone loss; cinacalcet was protective by univariate but not by multivariable analysis. CNS-affecting antihypertensives were protective against loss of BMD, cortical mass, cortical volume (ps < 0.05) and trabecular mass (p = 0.007). These effects remained after adjustment. BSAP correlated with changes in BMD, cortical mass, and volume (p < 0.01) as did sclerostin (inversely). CONCLUSIONS: There was severe cortical bone loss at the hip best recognized by QCT. Patients with shorter dialysis vintage and less pre-existing bone loss lost more bone, while treatment with CNS-acting antihypertensives was protective. BSAP and sclerostin were useful markers of bone loss. PMID- 28993867 TI - Efficacy of pelvic artery embolisation for severe postpartum hemorrhage. AB - PURPOSE: The purpose of our study was to evaluate the outcome of selective pelvic arterial embolisation (PAE) in women with severe postpartum hemorrhage (PPH). METHODS: We performed a retrospective, controlled, single-center cohort study. A total of 16 consecutive women with PPH who underwent therapeutic PAE were included. As historical control group, we included 22 women with similar severity of PPH who were managed without PAE. Outcome measures included necessity of surgical interventions such as postpartum hysterectomy and laparotomy after vaginal delivery, the amount of red blood cell transfusions, and hematologic findings after the procedure. RESULTS: PAE was successful in stopping PPH and preserving the uterus in all 16 women in the study group. No woman in the PAE group required a postpartum hysterectomy, whereas postpartum hysterectomy was unavoidable in two women in the control group. Laparotomy after vaginal delivery was necessary in two women of the group without embolisation. Hematologic parameters after the treatment were better in the PAE group than in the control group, although these differences were only in part statistically significant. There were no unwarranted effects of PAE identifiable in the study group. CONCLUSION: This is the first controlled study assessing the efficacy of PAE for the treatment of PPH. Our data suggest that PAE is effective for the treatment of severe PPH. In view of the lack of complications and unwarranted effects, clinical use of PAE in severe PPH seems justified, particularly in view of the life-threatening condition and the potential to preserve fertility in affected patients. Further evidence from well-designed prospective randomized-controlled trials would be nevertheless desirable in the future. PMID- 28993868 TI - [Dementia - View of sufferers and their relatives]. AB - Dementia is the leading cause of cognitive and functional impairment in old age; however, within the scientific community this complex disease is predominantly viewed from a narrow neurobiological and medical perspective, whereas the subjective aspects of dementia, particularly the psychological and social consequences, albeit severe are more or less neglected. In this article the subjective side of experiences of persons with dementia and their relatives are discussed and special aspects of their specific problems and needs during the course of the illness are described. The progress made in supporting persons with dementia and their carers during the last decades is considered and areas where further progress is necessary are delineated. PMID- 28993869 TI - Lack of silent cerebral ischemic events: a case series of patients after left atrial appendage closure. PMID- 28993870 TI - Serum serotonin levels and bone in rheumatoid arthritis patients. AB - In rheumatoid arthritis (RA), a disease characterized by bone loss, increased levels of serotonin have been reported. Recent studies have demonstrated a role for circulating serotonin as a regulator of osteoblastogenesis, inhibiting bone formation. Thus, we measured serum serotonin levels (SSL) in a Portuguese sample of 205 RA patients and related these to anthropometric variables, disease parameters, serum bone biomarkers, and bone mineral density (BMD) assessed by dual-energy X-ray absorptiometry at several sites (total proximal femur, lumbar spine, left hand, and left second proximal phalange). SSL were inversely associated with body mass index (BMI) in RA women (r = - 0.218; p = 0.005), independent of exposure to biologics and/or bisphosphonates. Among biologic naives, there was an inverse association between SSL and osteoprotegerin in RA women (r = - 0.260; p = 0.022). Serum beta-CTX and dickkopf-1 were strongly associated with SSL in RA men not treated with bisphosphonates (r = 0.590; p < 0.001/r = 0.387; p = 0.031, respectively). There was also an inverse association between SSL and sclerostin in RA men (r = - 0.374; p < 0.05), stronger among biologic naive or bisphosphonates-unexposed RA men. In crude models, SSL presented as a significant negative predictor of total proximal femur BMD in RA women as well as in postmenopausal RA women. After adjustment for BMI, disease duration, and years of menopause, SSL remained a significant negative predictor of total proximal femur BMD only in postmenopausal RA women. Our data reinforce a role, despite weak, for circulating serotonin in regulating bone mass in RA patients, with some differences in terms of gender and anatomical sites. PMID- 28993871 TI - Dual Bronchodilation with Indacaterol Maleate/Glycopyrronium Bromide Compared with Umeclidinium Bromide/Vilanterol in Patients with Moderate-to-Severe COPD: Results from Two Randomized, Controlled, Cross-over Studies. AB - PURPOSE: To compare the efficacy and safety of two long-acting dual bronchodilator combinations: indacaterol/glycopyrrolate (IND/GLY) versus umeclidinium/vilanterol (UMEC/VI). METHODS: Studies A2349 and A2350 were replicate, randomized, double-blind, double-dummy, active-controlled, cross-over studies in patients with moderate-to-severe COPD. Patients were randomized to sequential 12-week treatments of twice-daily IND/GLY 27.5/15.6 MUg and once-daily UMEC/VI 62.5/25 MUg, each separated by a 3-week washout. The primary objective was to demonstrate non-inferiority of IND/GLY compared with UMEC/VI in terms of the 24-h forced expiratory volume in 1 s profile at week 12 (FEV1 AUC0-24). Rescue medication use, symptom control, and safety were assessed throughout. RESULTS: Both treatments delivered substantial bronchodilation over 12 weeks, with improvements in FEV1 AUC0-24h at week 12 of 232 and 185 mL for IND/GLY, and 244 and 203 mL with UMEC/VI in Studies A2349 and A2350, respectively. The primary efficacy objective of non-inferiority of IND/GLY relative to UMEC/VI was not met as the lower bound of the confidence interval for the LS treatment comparison was below the pre-specified non-inferiority margin of -20 mL in both studies: -26.9 and -34.2 mL, respectively (LS mean between-treatment differences: -11.5 and 18.2 mL). Both drugs were well tolerated, with AE profiles consistent with their respective prescribing information. CONCLUSIONS: IND/GLY and UMEC/VI provided clinically meaningful and comparable bronchodilation. Non-inferiority of IND/GLY to UMEC/VI could not be declared although between-treatment differences were not clinically relevant. The data support the use of IND/GLY as an efficacious and well tolerated treatment option in patients with COPD. (ClinicalTrials.gov NCT02487446 and NCT02487498). PMID- 28993872 TI - A novel mutation of VAPB in one Chinese familial amyotrophic lateral sclerosis pedigree and its clinical characteristics. AB - The mutation of vesicle-associated membrane protein-associated protein B (VAPB) was proved to cause family amyotrophic lateral sclerosis (FALS). Only two mutations of VAPB associated with ALS have been reported (p.Pro56Ser and p.Thr46Ile). Here we reported a Chinese Han FALS family caused by a novel VAPB point mutation. The clinical materials of one Chinese Han FALS family were collected. The genetic analysis was carried out by target sequencing and further verified by Sanger sequencing. One novel mutation of c.167C>A (p.Pro56His) on VAPB was found in the proband. The age at onset of the proband was 48 with the onset symptoms of weakness in the right arm, followed by progressive limb and trunk weakness with decreased deep-tendon reflexes, muscular cramps and fasciculation. But the disease duration was more than 15 years. He was under the tracheotomy for 1 year at last visit. Electromyography showed widespread acute and chronic neurogenic damages. His mother presented weakness in her limbs in 50 s and died 15 years later. One of his younger sisters diagnosed as ALS for 6 years also carried the same mutation. She presented the similar symptoms on 41. No dominant upper motor neuron sign was showed. The clinical features were similar to the patients carrying the known mutation of p.Pro56Ser. A novel mutation of VAPB was found in one Chinese Han FALS pedigree. The affected patients presented a much slower progression and the lesions were limited in lower motor neurons. PMID- 28993873 TI - Heart rate variability decreases after 3 months of sustained treatment with fingolimod. AB - The objective is to prospectively investigate short- and mid-term changes of heart rate variability (HRV) in patients with relapsing-remitting multiple sclerosis (RRMS), being started on fingolimod. In this prospective clinical trial, patient (n = 33) with RRMS starting treatment with fingolimod underwent a time-domain-based analysis of HRV (breathing at rest, deep breath, and in response to the Valsalva maneuver) shortly before, 4.5 h and 3 months after first intake. Blood pressure changes after the Valsalva maneuver were used as a marker of the sympathetic noradrenergic system. We used a non-invasive continuous beat to-beat heart rate and blood pressure monitoring. In addition, the Fatigue Severity Scale and the refined and abbreviated Composite Autonomic Symptom Score were applied. Significant changes in HRV in RRMS patients, following treatment with fingolimod, were detected. After an initial increase in HRV, measured 4.5 h after the first intake of fingolimod, a substantial decrease in HRV occurred within 3 months on continuous treatment. There is a growing body of evidence for short-term cardiovascular side effects in continuous treatment with fingolimod, driven by the ANS. The mechanisms and the clinical relevance of the observed changes in HRV need further evaluation, especially in longer and larger prospective studies. PMID- 28993874 TI - Prognosis of patients with primary malignant brain tumors admitted to the intensive care unit: a two-decade experience. AB - The purpose of this study is to describe the reasons for ICU admission and to evaluate the outcome and prognostic factors of patients with primary malignant brain tumors (PMBT) admitted to the intensive care unit (ICU). This is a retrospective observational cohort study of 196 PMBT patients admitted to two ICUs over a 19-year period. Acute respiratory failure was the main reason for ICU admission (45%) followed by seizures (25%) and non-epileptic coma (14%). Seizures were more common in patients with glial lesions (84 vs. 67%), whereas patients with primary brain lymphoma were more frequently admitted for shock (42 vs. 18%). Overall ICU and 90-day mortality rates were 23 and 50%, respectively. Admission for seizures was independently associated with lower ICU mortality [odds ratio (OR) 0.06], whereas the need for mechanical ventilation (OR 6.85), cancer progression (OR 7.84), respiratory rate (OR 1.11) and Glasgow coma scale (OR 0.85) were associated with higher ICU mortality. Among the 95 patients who received invasive mechanical ventilation, ICU mortality was 37% (n = 35). For these patients, admission for seizures was associated with lower ICU mortality (OR 0.050) whereas cancer progression (OR 7.49) and respiratory rate (OR 1.08) were associated with higher ICU mortality. The prognosis of PMBT patients admitted to the ICU appears relatively favorable compared to that of hematologic malignancies or solid tumors, especially when the patient is admitted for seizures. The presence of a PMBT, therefore, does not appear to be sufficient for refusal of ICU admission. Predictive factors of mortality may help clinicians make optimal triage decisions. PMID- 28993875 TI - Suicidality is a common and serious feature of anti-N-methyl-D-aspartate receptor encephalitis. AB - We aimed to assess suicidality risk amongst people who had had anti-N-methyl-D aspartate receptor (NMDAR) encephalitis. All people with a definitive diagnosis of anti-NMDAR encephalitis in West China Hospital between June 2012 and February 2017 were identified and their notes were retrospectively reviewed. Demographic and clinical characteristics and risk predictors for suicidality were summarized; those with suicidality were compared to those without. 17 of 133 people (13%) presented with suicidality symptoms: 7 (5%) with suicidal ideation; 8 (6%) who attempted suicide; and 2 (1.5%) who completed suicide. Median age was 27 (16-78) years, most were female [13 (76%)]. Compared with those with no suicidality, psychiatric symptoms as the initial symptoms were more frequent in those who reported suicidality (p = 0.039); insomnia, aggression, mania, depression and delusion were also more common (p < 0.05). The use of antidepressants (p < 0.001) and recurrence of encephalitis (p = 0.020) were higher in people with suicidality than in those without. Other characteristics were not significantly different in those who had suicidality and those who did not. Suicidality is a common and potentially lethal risk for people with anti-NMDAR encephalitis. Those presenting with psychiatric symptoms as the initial symptom and with insomnia, aggression, mania, depression and delusion should be carefully screened for suicidality. Closely monitoring people who have been treated with antidepressants is necessary. PMID- 28993876 TI - IL-8 Gene Variants and Expression in Childhood Asthma. AB - PURPOSE: To examine the IL-8 expression levels and association of genetic variants with the risk of childhood persistent asthma prognosis. METHODS: Overall, 170 asthmatic children and 170 healthy controls were included in this case-control study. The human IL-8 serum levels were measured using ELISA. The IL 8 mRNA expression levels were assessed by a real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. RESULTS: The IL-8 expression at both protein and mRNA levels was found to be significantly elevated in asthmatic children compared to healthy subjects (P < 0.0001, P = 0.004; respectively). Higher levels of IL-8 mRNA are detected in subjects with moderate to severe asthma. The presence of IL8-251 A/T (rs4073) and + 781C/T (rs2227306) polymorphisms was significantly associated with an increased risk of asthma (P = 0.002, P = 0.036, respectively). In addition, we noted a significant association between these polymorphisms and an elevated risk of atopic asthma (P < 0.05). For rs2227306 SNP, the highest median level of IgE was detected for the presence of TT genotype (865 +/- 99.74 IU/mL). Although, the rs4073 polymorphism conferred a higher risk to develop asthma at an advanced stage of severity (P = 0.008). The rs4073 T and rs2227306 C alleles are considered as risk factors for asthma development. The rs4073 T allele is represented also as a risk factor for asthma severity in Tunisian children. CONCLUSIONS: Both IL-8 gene and protein expression may play a key role in asthma pathogenesis. PMID- 28993877 TI - Anxiety, Depression, and Health-Related QOL in Patients Diagnosed with PAH or CTEPH. AB - BACKGROUND: Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are life-threatening diseases with a high burden of symptoms. Although depression, anxiety, and reduced health related quality of life (HRQOL) have also been reported, a comparative analysis which explores these traits and their underlying factors was lacking. METHODS: A retrospective analysis of depression, anxiety, and health related QOL was conducted using a Hospital anxiety and depression scale (HADS) as well as the SF-36 HRQOL questionnaire. Results from these tools were compared with haemodynamic and functional parameters in 70 PAH and 23 CTEPH outpatients from a German tertiary care center specializing in pulmonary hypertension. RESULTS: Although HRQOL was reduced in both cohorts of patients, individuals diagnosed with CTEPH scored lower in nearly all SF-36 parameters. Significance was noted in both "mental health" (p = 0.01) and "mental component summary score" (MCS) (p = 0.02). Depression was also more frequent in patients with CTEPH (56%) than in patients with PAH (30%), (p = 0.03). Overall, depression and anxiety correlated with most SF-36 scales in both PAH and CTEPH. In CTEPH, depression also correlated with the Borg Dyspnea Scale (r = 0.44, p = 0.01). These patients also had significantly lower pCO2 levels than the PAH cohort reflecting more severe ventilation/perfusion mismatch. All other haemodynamic and functional parameters did not differ across the groups. CONCLUSION: While both cohorts of patients suffer from a reduced HRQOL as well as depression and anxiety, decreases in mental health parameters are more pronounced in the CTEPH cohort. This suggests a strong effort to improve early detection, especially in dyspneic patients with classical risk factors for CTEPH and PAH and argues for mental illness interventions alongside routine clinical care provided to patients diagnosed with PAH or CTEPH. PMID- 28993878 TI - Fuzzy neuronal model of motor control inspired by cerebellar pathways to online and gradually learn inverse biomechanical functions in the presence of delay. AB - Contrary to forward biomechanical functions, which are deterministic, inverse biomechanical functions are generally not. Calculating an inverse biomechanical function is an ill-posed problem, which has no unique solution for a manipulator with several degrees of freedom. Studies of the command and control of biological movements suggest that the cerebellum takes part in the computation of approximate inverse functions, and this ability can control fast movements by predicting the consequence of current motor command. Limb movements toward a goal are defined as fast if they last less than the total duration of the processing and transmission delays in the motor and sensory pathways. Because of these delays, fast movements cannot be continuously controlled in a closed loop by use of sensory signals. Thus, fast movements must be controlled by some open loop controller, of which cerebellar pathways constitute an important part. This article presents a system-level fuzzy neuronal motor control circuit, inspired by the cerebellar pathways. The cerebellar cortex (CC) is assumed to embed internal models of the biomechanical functions of the limb segments. Such neural models are able to predict the consequences of motor commands and issue predictive signals encoding movement variables, which are sent to the controller via internal feedback loops. Differences between desired and expected values of variables of movements are calculated in the deep cerebellar nuclei (DCN). After motor learning, the whole circuit can approximate the inverse function of the biomechanical function of a limb and acts as a controller. In this research, internal models of direct biomechanical functions are learned and embedded in the connectivity of the cerebellar pathways. Two fuzzy neural networks represent the two parts of the cerebellum, and an online gradual learning drives the acquisition of the internal models in CC and the controlling rules in DCN. As during real learning, exercise and repetition increase skill and speed. The learning procedure is started by a simple and slow movement, controlled in the presence of delays by a simple closed loop controller comparable to the spinal reflexes. The speed of the movements is then increased gradually, and output error signals are used to compute teaching signals and drive learning. Repetition of movements at each speed level allows to properly set the two neural networks, and progressively learn the movement. Finally, conditions of stability of the proposed model as an inverter are identified. Next, the control of a single segment arm, moved by two muscles, is simulated. After proper setting by motor learning, the circuit is able to reject perturbations. PMID- 28993879 TI - Accuracy of Diagnostic Coding for Sarcoidosis in Electronic Databases: A Population-Based Study. AB - PURPOSE: Epidemiologic study of sarcoidosis utilizing electronic databases has been increasingly popular. However, the accuracy of diagnostic codes for sarcoidosis is unknown. METHODS: The medical record-linkage system of the Rochester Epidemiology Project was searched to identify all potential adult cases of sarcoidosis between January 1, 1995 and December 31, 2013 in Olmsted County, Minnesota, using the International Classification of Diseases, Ninth Revision (ICD-9) code 135 (sarcoidosis). Complete medical records of those potential cases were individually reviewed. The diagnosis of sarcoidosis was confirmed by the presence of non-caseating granuloma on histopathology, radiographic findings of intrathoracic sarcoidosis, and compatible clinical presentations. Positive predictive value (PPV) was estimated as the number of patients verified to have sarcoidosis divided by the number of patients with a diagnostic code for sarcoidosis. RESULTS: The study cohort included 366 patients with at least one code for sarcoidosis. Of these, 224 cases of confirmed sarcoidosis were identified, resulting in PPV of 61.2% (95% CI 56.0-66.2%). A total of 268 patients in the database had a code for sarcoidosis on least two occasions separated by at least 30 days. Of these, there were 205 cases of confirmed sarcoidosis. The PPV for having the code at least twice was 76.5% (95% CI 71.0 81.4%). CONCLUSIONS: The PPV of ICD-9 code for sarcoidosis is relatively low and, thus, further verification is required for studies using electronic databases. PMID- 28993882 TI - Commuter exposure to fine and ultrafine particulate matter in Vienna. AB - Mass concentrations PM10, PM2.5, PM1, particle number concentrations of ultrafine particles and lung deposited surface area were measured during commutes with a subway, tram, bus, car and bicycle in Vienna for the first time. Obtained data were examined for significant differences in personal exposure when using various transport modalities along similar routes. Mean PM2.5 and PM1 mass concentrations were significantly higher in the subway when compared to buses. Mean PM10, PM2.5 and PM1 mass concentrations were significantly higher in the subway when compared to cars using low ventilation settings. Particle number concentrations of ultrafine particles were significantly higher in trams when compared to the subway and lung deposited surface area was significantly greater on bicycles when compared to the subway. After adjusting for different vehicle speeds, exposure to PM10, PM2.5 and PM1 along the same route length was significantly higher in the subway when compared to cars while exposure to ultrafine particles and partly also lung deposited surface area was significantly higher in bus, tram and on bicycle when compared to the subway. Car and bus passengers could be better isolated from ambient fine particulate matter than passengers in the subway, where a lot of ventilation occurs through open windows and larger doors. Tram passengers and cyclists might be exposed to increased amounts of ultrafine particles and larger lung deposited surface area due to a closer proximity to road traffic. Comparing cumulative exposure along the same route length leads to different results and favors faster traffic modes, such as the subway. PMID- 28993881 TI - Maximal rate of heart rate increase correlates with fatigue/recovery status in female cyclists. AB - PURPOSE: Being able to identify how an athlete is responding to training would be useful to optimise adaptation and performance. The maximal rate of heart rate increase (rHRI), a marker of heart rate acceleration has been shown to correlate with performance changes in response to changes in training load in male athletes; however, it has not been established if it also correlates with performance changes in female athletes. METHODS: rHRI and cycling performance were assessed in six female cyclists following 7 days of light training (LT), 14 days of heavy training (HT) and a 10 day taper period. rHRI was the first derivative maximum of a sigmoidal curve fit to R-R data recorded during 5 min of cycling at 100 W. Cycling performance was assessed as work done (kJ) during time trials of 5 (5TT) and 60 (60TT) min duration. RESULTS: 5TT was possibly decreased at HT (ES +/- 90% confidence interval = - 0.16 +/- 0.25; p = 0.60), while, 5TT and 60TT very likely to almost certainly increased from HT to taper (ES = 0.71 +/ 0.24; p = 0.007 and ES = 0.42 +/- 0.19; p = 0.02, respectively). Large within subject correlations were found between rHRI, and 5TT (r = 0.65 +/- 0.37; p = 0.02) and 60TT (r = 0.70 +/- 0.31; p = 0.008). CONCLUSIONS: rHRI during the transition from rest to light exercise correlates with training induced-changes in exercise performance in females, suggesting that rHRI may be a useful monitoring tool for female athletes. PMID- 28993880 TI - Effects of prenatal caffeine exposure on glucose homeostasis of adult offspring rats. AB - Epidemiological evidences show that prenatal caffeine exposure (PCE) could induce intrauterine growth retardation (IUGR). The IUGR offspring also present glucose intolerance and type 2 diabetes mellitus after maturity. We have previously demonstrated that PCE induced IUGR and increased susceptibility to adult metabolic syndrome in rats. This study aimed to further investigate the effects of PCE on glucose homeostasis in adult offspring rats. Pregnant rats were administered caffeine (120 mg/kg/day, intragastrically) from gestational days 11 to 20. PCE offspring presented partial catch-up growth pattern after birth, characterizing by the increased body weight gain rates. Meanwhile, PCE had no significant influences on the basal blood glucose and insulin phenotypes of adult offspring but increased the glucose tolerance, glucose-stimulated insulin section and beta cell sensitivity to glucose in female progeny. The insulin sensitivity of both male and female PCE offspring were enhanced accompanied with reduced beta cell fraction and mass. Western blotting results revealed that significant augmentation in protein expression of hepatic insulin signaling elements of PCE females, including insulin receptor (INSR), insulin receptor substrate 1 (IRS-1) and the phosphorylation of serine-threonine protein kinase (Akt), was also potentiated. In conclusion, we demonstrated that PCE reduced the pancreatic beta mass but increased the glucose tolerance in adult offspring rats, especially for females. The adaptive compensatory enhancement of beta cell responsiveness to glucose and elevated insulin sensitivity mainly mediated by upregulated hepatic insulin signaling might coordinately contribute to the increased glucose tolerance. PMID- 28993883 TI - Shaping somatosensory responses in awake rats: cortical modulation of thalamic neurons. AB - Massive corticothalamic afferents originating from layer 6a of primary sensory cortical areas modulate sensory responsiveness of thalamocortical neurons and are pivotal for shifting neuronal firing between burst and tonic modes. The influence of the corticothalamic pathways on the firing mode and sensory gain of thalamic neurons has only been extensively examined in anesthetized animals, but has yet to be established in the awake state. We made lesions of the rat barrel cortex and on the following day recorded responses of single thalamocortical and thalamic reticular neurons to a single vibrissal deflection in the somatosensory system during wakefulness. Our results showed that the cortical lesions shifted the response of thalamic neurons towards bursting, elevated the response probability and the gain of thalamocortical neurons, predominantly of recurring responses. In addition, after the lesions, the spontaneous activities of the vibrissa-responsive thalamic neurons, but not those of vibrissa-unresponsive cells, were typified by waxing-and-waning spindle-like rhythmic spiking with frequent bursting. In awake rats with intact cortex, identified layer 6a corticothalamic neurons responded to a single vibrissal deflection with short latencies that matched those of layer 4 neurons, strongly suggesting the existence of an immediate corticothalamic feedback. The present results show the importance of corticothalamic neurons in shaping thalamic activities during wakefulness. PMID- 28993884 TI - Responsiveness of the EuroQoL 5-dimension (EQ-5D) in adolescent idiopathic scoliosis. AB - PURPOSE: To test the responsiveness of the EuroQoL 5-dimension (EQ-5D) utility scores for adolescent idiopathic scoliosis (AIS). METHODS: A baseline sample of 227 AIS patients was recruited between August and October 2015, and was surveyed prospectively to 9-12 months follow-up. EQ-5D-5L utility scores were derived using a two-step approach: (1) cross-walking from five-level responses to three level responses and (2) applying the EQ-5D-3L Chinese population value set. An anchor approach was adopted to assess the responsiveness of EQ-5D. Effect size statistics (standardized effect size and standardized response mean) and independent t test were used to assess the responsiveness, as well as to analyze the ability of measures to detect score changes with global health condition changes or discriminate between the worsened and unchanged/improved groups. RESULTS: Approximately two-thirds of follow-up patients (64.2%) reported no change in global health condition based on the self-reported health anchor, whilst 4.6 and 31.3% of patients rated worse and better in current health condition compared to baseline, respectively. In the subgroup where health worsened, EQ-5D utility scores were responsive to detect negative changes. EQ-5D utility scores had slight improvement in the group where health improved, despite a high mean score of 0.92 at baseline. Neither statistical significance nor moderate-large effect size was observed in mean changes among unchanged group. Responsiveness property of the EQ-5D utility score was generally satisfactory with respect to each health condition group. CONCLUSIONS: EQ-5D is found to be able to capture positive changes, and responsive in detecting important clinical changes in the improved group of this AIS population. PMID- 28993885 TI - Gait variability predicts a subset of falls in cerebellar gait disorders. PMID- 28993886 TI - Thrombotic microangiopathy following haematopoietic stem cell transplant. AB - Thrombotic microangiopathy is a potentially lethal complication of haematopoietic stem cell (bone marrow) transplantation. The pathophysiology is incompletely understood, although endothelial damage appears to be central. Platelet activation, neutrophil extracellular traps and complement activation appear to play key roles. Diagnosis may be difficult and universally accepted diagnostic criteria are not available. Treatment remains controversial. In some cases, withdrawal of calcineurin inhibitors is adequate. Rituximab and defibrotide also appear to have been used successfully. In severe cases, complement inhibitors such as eculizumab may play a valuable role. Further research is required to define the pathophysiology and determine both robust diagnostic criteria and the optimal treatment. PMID- 28993887 TI - The effect of everolimus on renal angiomyolipoma in pediatric patients with tuberous sclerosis being treated for subependymal giant cell astrocytoma. AB - BACKGROUND: Patients with tuberous sclerosis complex (TSC) often have multiple TSC-associated hamartomas, particularly in the brain and kidney. METHODS: This was a post hoc analysis of pediatric patients being treated for subependymal giant cell astrocytomas (SEGAs) during the phase 3, randomized, double-blind, placebo-controlled EXIST-1 trial. Patients were initially randomly assigned to receive everolimus 4.5 mg/m2/day (target blood trough 5-15 mg/dl) or placebo and could continue in an open-label extension phase. Angiomyolipoma response rates were analyzed in patients aged <18 years with >=1 target angiomyolipoma lesion at baseline. Response was defined as the proportion of patients with a >=50% reduction in the sum volume of target renal angiomyolipomata from baseline, in the absence of new target angiomyolipomata, a >20% increase in kidney volume from nadir, and angiomyolipoma-related bleeding >= grade 2. Tolerability was also assessed. RESULTS: Overall, this analysis included 33 patients. Renal angiomyolipoma response was achieved by 75.8% of patients (95% confidence interval, 57.7-88.9%), with sustained mean reductions in renal angiomyolipoma volume over nearly 4 years of treatment. In addition, most (>=80%) achieved clinically relevant reductions in angiomyolipoma volume (>=50%), beginning at week 24 and continuing for the remainder of the study. Everolimus was generally well tolerated in this subgroup, with most adverse events being grade 1 or 2 in severity. CONCLUSIONS: Although everolimus is currently not indicated for this use, this analysis from EXIST-1 demonstrates its long-term efficacy and safety for the treatment of renal angiomyolipoma in pediatric patients undergoing treatment for TSC-associated SEGA. PMID- 28993888 TI - Oncologists' responses to patient and caregiver negative emotions and patient perception of quality of communication: results from a multi-ethnic Asian setting. AB - PURPOSE: Patients with advanced cancer and their caregivers experience many negative emotions. Empathic responses from oncologists can help alleviate their distress. We aimed to assess expressions of negative emotions among patients with advanced cancer and their caregivers and oncologists' empathic responses during consultations in an Asian setting. We also assessed the association between oncologists' expression of empathy and patients' and caregivers' perception of communication quality. METHODS: We surveyed 100 patients with advanced cancer and their caregivers and audio recorded consultations with their oncologists. We coded expressions of negative emotions by patients and caregivers and oncologists' empathic responses. We also surveyed participating oncologists (n = 30) about their confidence in expressing empathy and perceived communication behavior outcomes. RESULTS: About 52% of patients and 49% of caregivers expressed at least one negative emotion during the consultation, though 59% of patients and 48% of caregivers reported not wanting to discuss negative emotions. Oncologists responded empathically to 12% of patients' negative emotions and 9% of caregivers' negative emotions, despite 92% of them reporting confidence in expressing empathy. Oncologists' expression of empathy did not vary significantly by patient, caregiver, or their own demographic characteristics. It also did not differ based on their confidence in expressing empathy and positive outcome expectations. When oncologists responded empathically just one time, patients perceived communication more favorably. CONCLUSIONS: In this Asian setting, patients and caregivers commonly expressed negative emotions. Oncologists' expressed empathy infrequently, although when they were empathic, it was related to improved patient perception of communication quality. PMID- 28993889 TI - Recurrent primary osseous hemangiopericytoma in the thoracic spine: a case report and literature review. AB - PURPOSE: Primary osseous hemangiopericytoma (HPC) of the spine is exceedingly rare. HPC has malignant potential and has the capacity for metastasis and local recurrence. We herein present the first case of recurrent primary osseous HPC in the thoracic spine that was successfully treated by total spondylectomy at three vertebral levels and spinal reconstruction. METHODS: We performed a two-stage operation for recurrent HPC using anterior and posterior approaches at the T5-T7 vertebrae. The preoperative embolization of the tumor was performed to prevent massive intraoperative bleeding. Then, total spondylectomy was performed (T5-T7) to resect the tumor. Anterior spinal reconstruction and posterior instrumentation were performed, with abundant bone autograft and allograft used to achieve sufficient boney fusion following the removal of the tumor. RESULTS: At 2 years after surgery, the patient had made a sufficient recovery from his symptoms. The bone union was complete without tumor recurrence or implant failure. CONCLUSIONS: Total spondylectomy and spinal reconstruction with instrumentation might be useful for performing the safe and adequate excision of recurrent HPC of the spine. However, patients should be closely monitored to detect local recurrence and the malignant degeneration of the tumor after surgery. PMID- 28993890 TI - Resting GABA concentration predicts inhibitory control during an auditory Go-Nogo task. AB - Inhibitory control plays an important role in goal-directed behavior. Although substantial inter-individual variability exists in the behavioral performance of response inhibition, the corresponding modulating neurochemical and neurophysiological mechanisms remain unclear. Thus, the present study aimed to explore the relationship between behavioral response inhibition, GABA+ concentrations and automatic sensory gating (SG) in the auditory cortices. We recruited 19 healthy adults to undergo magnetoencephalography, magnetic resonance spectroscopy (MRS), and behavioral experiments. A paired-stimulus paradigm was used to study SG of the auditory cortices, and an auditory-driven Go-Nogo task was used to evaluate the behavioral response inhibition. Resting GABA+ concentrations were measured in the bilateral superior temporal gyri by means of MRS. Neither GABA+ concentrations nor auditory SG showed significant hemispheric asymmetry. However, an enhanced SG (lower ratio) was found to correlate with improved behavioral inhibition. Moreover, a higher GABA+ concentration was strongly related to improved inhibitory control. These findings highlight the important role of automatic neurophysiological processes and inhibitory neurotransmitters in the prediction of the behavioral performance of inhibitory control. PMID- 28993891 TI - Value of antibiotic prophylaxis in routine knee arthroscopy : A retrospective study. AB - OBJECTIVE: Prophylactic antibiotic use prior to routine knee arthroscopy remains controversial. It is important to know whether antibiotics help decrease the surgical site infection (SSI) rate. Our aims were to assess the efficacy of antibiotic prophylaxis in preventing SSI and to identify risk factors for SSI following routine knee arthroscopy without an implant. METHODS: A retrospective study was conducted using the electronic medical records at the authors' hospital to identify patients that underwent routine knee arthroscopy without an implant between October 2010 and October 2016. Data on demographics, clinical characteristics and antibiotic administration were extracted. Arthroscopic diagnosis, debridement, partial or complete meniscectomy, arthroscopic shaving and microfracture, removal of loose bodies, synovectomy and lateral retinacular release were included. Complex knee arthroscopy with an implant was excluded. Patients were divided into evaluation (with prophylactic antibiotics) and control (no antibiotic treatment) groups. Continuous variables between groups were compared using the Student's t-test. Data were analyzed using the Chi-squared test for percentages between groups. Multivariate logistic regression was used to identify independent risk factors of SSI. RESULTS: Of 1326 patients, 614 (46.3%) received prophylactic antibiotics, while 712 (53.7%) did not. There were seven (0.53%) SSIs. The SSI rate did not differ significantly between patients receiving antibiotics (0.49%, three) and those not (0.56%, four). Five patients (0.37%) had superficial infections, two (0.33%) were in the prophylactic antibiotic group and three (0.42%) were in the other group. Deep infections occurred in two patients (0.15%), one (0.16%) in the prophylactic antibiotic group and one (0.14%) in the other group. The difference between the two groups was not statistically significant (P = 1.0). Age over 50 years was associated with an increased risk of SSI (relative ratio [RR] = 1.469, 95% confidence interval [CI] 1.09-2.13, P = 0.009). CONCLUSIONS: Prophylactic antibiotic use in routine knee arthroscopy without an implant may not be necessary. Age over 50 years was associated with an increased risk of SSI. PMID- 28993892 TI - Screening investigations in small-for-gestational-age near-term and term infants. AB - : The aims of this study are to examine how frequently near-term and term small for-gestational-age (SGA) infants were investigated in our clinical practice, whether being born less than the third centile for weight increased the yield of positive investigations, and whether there were additional characteristics in infants with positive investigations. This retrospective cohort study was compiled using a database of a large maternity network, using the search near term and term gestational age (greater than or equal to 35 weeks) over a span of 4 years. SGA babies were further filtered into less than the tenth centile and third centile. Out of a population of 30,461 infants in the study period, 3437 (11.3%) SGA infants were identified. Four hundred fifteen SGA infants (12.1%) underwent screening investigations, of which 49 infants (11.8%) yielded a positive investigation. 27.2% of karyotypes, 12.8% of cranial ultrasounds and 0.4% of urine CMV tests showed positive results in < 10th centile group. Being born less than the third centile for weight did not increase the yield of positive investigations. Most infants with positive investigations had an additional maternal or neonatal characteristic or risk factor present. CONCLUSION: SGA babies without additional maternal or neonatal characteristics have a poor yield on neonatal screening investigations. Additional characteristics may be considered while deciding whether a SGA infant needs screening investigation. What is Known: * Small-for-gestational-age (SGA) infants have an increased risk of short- and long-term complications. * Whilst the causes for SGA are multifactorial, there has been a tendency to undertake screening investigations like Toxoplasma, Others, Rubella, Cytomegalovirus, Herpes group of viruses (TORCH) screening and cranial ultrasounds in the neonatal period. What is New: * Comprehensive study investigating the rates of screening in near-term and term SGA population. * The yield of screening tests for near-term and term SGA infants without additional antenatal and postnatal characteristics is low. PMID- 28993893 TI - Identification of arbuscular mycorrhiza-inducible Nitrate Transporter 1/Peptide Transporter Family (NPF) genes in rice. AB - Arbuscular mycorrhizal fungi (AMF) colonize up to 90% of all land plants and facilitate the acquisition of mineral nutrients by their hosts. Inorganic orthophosphate (Pi) and nitrogen (N) are the major nutrients transferred from the fungi to plants. While plant Pi transporters involved in nutrient transfer at the plant-fungal interface have been well studied, the plant N transporters participating in this process are largely unknown except for some ammonium transporters (AMT) specifically assigned to arbuscule-colonized cortical cells. In plants, many nitrate transporter 1/peptide transporter family (NPF) members are involved in the translocation of nitrogenous compounds including nitrate, amino acids, peptides and plant hormones. Whether NPF members respond to AMF colonization, however, is not yet known. Here, we investigated the transcriptional regulation of 82 rice (Oryza sativa) NPF genes in response to colonization by the AMF Rhizophagus irregularis in roots of plants grown under five different nutrition regimes. Expression of the four OsNPF genes NPF2.2/PTR2, NPF1.3, NPF6.4 and NPF4.12 was strongly induced in mycorrhizal roots and depended on the composition of the fertilizer solution, nominating them as interesting candidates for nutrient signaling and exchange processes at the plant-fungal interface. PMID- 28993894 TI - The association of lumbar intervertebral disc calcification on plain radiographs with the UTE Disc Sign on MRI. AB - PURPOSE: The pathogenesis and the clinical impact of disc calcification are not well known. Utilizing ultra-short time-to-echo (UTE) magnetic resonance imaging, the UTE Disc Sign (UDS) (i.e., hypo/hyper-intense disc band) was developed and found to be more significantly related to pain and disability than the conventional T2-weighted (T2W) MRI. It has been hypothesized that the UDS may represent mineralized deposits in the disc. The following study addressed the relationship between disc calcification on plain radiographs to that of the UDS on MRI. METHODS: A cross-sectional study was performed on 106 Southern Chinese subjects (50% male; mean age 52.3 years). Standing lateral plain radiographs as well as T2W and UTE MRI of L1-S1 (n = 530 discs) were performed of all subjects. Lateral radiographs were used to localize disc calcification of the lumbar spine, T2W MRI was utilized to assess disc degeneration based on a defined grading scheme, and the UTE MRI was implemented to detect the UDS (hyper- or hypo-intense band across a disc). Disc degeneration and UDS scores were summed to represent cumulative scores. Subject demographics and disability profiles (Oswestry Disability Index: ODI) were obtained. RESULTS: Disc calcification on plain radiographs was observed in 33.9% of subjects (55.5% males; mean age 54.3 years), whereas UDS was noted in 40.5% of subjects (51.1% males; mean age 55.0 years). Of these subjects, 66.6% calcification and 74.4% UDS occurred at the three lowest lumbar levels, while multilevel calcification and UDS involved 19.4 and 39.5%, respectively. 72.2% of subjects with plain radiographic disc calcification had corresponding UDS on UTE MRI (p < 0.001). Multilevel disc calcification on plain radiographs was associated with multilevel UDS (71.4%, p < 0.001). Both the number of calcified disc levels on plain radiographs and the number of UDS levels were also significantly and positively correlated with each other (r = 0.58, p < 0.001). Subjects with disc calcification and positive UDS as well as individuals with increased disc degeneration scores on T2 W MRI were significantly older (p < 0.05). The cumulative UDS score on UTE MRI significantly correlated with worse ODI scores (r = 0.31; p = 0.001), whereas cumulative disc calcification scores on plain radiographs did not (r = 0.15; p = 0.19). CONCLUSIONS: This is the first study to compare the UDS on UTE MRI with disc calcification on plain radiographs. Disc calcification was correlated with the UDS on UTE, suggesting that the UDS may represent disc calcification. However, UTE MRI appears to be a more sensitive imaging modality in identifying subtle and unique disc changes that may not be revealed on plain radiographs or conventional MRI. This disconnect may rationalize the significant correlation of UTE with disability in comparison with the conventional imaging, further stressing its potential clinical importance. PMID- 28993895 TI - Subcellular localization and function of 2LIM proteins in plants and humans. PMID- 28993896 TI - RCAN1 Mutation and Functional Characterization in Children with Sporadic Congenital Heart Disease. AB - Congenital heart disease (CHD) is the most frequent birth defect. RCAN1 (regulator of calcineurin 1) contributes to CHD in Down syndrome. However, whether RCAN1 is also associated with nonsyndromic CHD remains unclear. This study sequenced the exons and flanking region of RCAN1 in 128 sporadic CHD patients and 150 normal controls. We identified six novel heterozygous mutations in CHD patients. Functional assay showed that the g.482G>T could obviously raise the promoter activity of RCAN1.4 in vitro; However, we failed to detect the expression of RCAN1 in the right auricle, which made it confused to evaluate the pathogenicity of this mutation. In addition, we demonstrated that c.290T>C and g.1056+58C>A had no effect on the alternative splicing of RCAN1. The *196C>T, *790G>A, and *1278C>G did not influence the translation of RCAN1 post transcription. In conclusion, a novel mutation of g.482G>T in RCAN1 may be related to CHD by causing overexpression of RCAN1.4. PMID- 28993897 TI - Quantitative Image Feature Engine (QIFE): an Open-Source, Modular Engine for 3D Quantitative Feature Extraction from Volumetric Medical Images. AB - The aim of this study was to develop an open-source, modular, locally run or server-based system for 3D radiomics feature computation that can be used on any computer system and included in existing workflows for understanding associations and building predictive models between image features and clinical data, such as survival. The QIFE exploits various levels of parallelization for use on multiprocessor systems. It consists of a managing framework and four stages: input, pre-processing, feature computation, and output. Each stage contains one or more swappable components, allowing run-time customization. We benchmarked the engine using various levels of parallelization on a cohort of CT scans presenting 108 lung tumors. Two versions of the QIFE have been released: (1) the open-source MATLAB code posted to Github, (2) a compiled version loaded in a Docker container, posted to DockerHub, which can be easily deployed on any computer. The QIFE processed 108 objects (tumors) in 2:12 (h/mm) using 1 core, and 1:04 (h/mm) hours using four cores with object-level parallelization. We developed the Quantitative Image Feature Engine (QIFE), an open-source feature-extraction framework that focuses on modularity, standards, parallelism, provenance, and integration. Researchers can easily integrate it with their existing segmentation and imaging workflows by creating input and output components that implement their existing interfaces. Computational efficiency can be improved by parallelizing execution at the cost of memory usage. Different parallelization levels provide different trade-offs, and the optimal setting will depend on the size and composition of the dataset to be processed. PMID- 28993898 TI - Dynamic transcriptomic analysis in hircine longissimus dorsi muscle from fetal to neonatal development stages. AB - Muscle growth and development from fetal to neonatal stages consist of a series of delicately regulated and orchestrated changes in expression of genes. In this study, we performed whole transcriptome profiling based on RNA-Seq of caprine longissimus dorsi muscle tissue obtained from prenatal stages (days 45, 60, and 105 of gestation) and neonatal stage (the 3-day-old newborn) to identify genes that are differentially expressed and investigate their temporal expression profiles. A total of 3276 differentially expressed genes (DEGs) were identified (Q value < 0.01). Time-series expression profile clustering analysis indicated that DEGs were significantly clustered into eight clusters which can be divided into two classes (Q value < 0.05), class I profiles with downregulated patterns and class II profiles with upregulated patterns. Based on cluster analysis, GO enrichment analysis found that 75, 25, and 8 terms to be significantly enriched in biological process (BP), cellular component (CC), and molecular function (MF) categories in class I profiles, while 35, 21, and 8 terms to be significantly enriched in BP, CC, and MF in class II profiles. KEGG pathway analysis revealed that DEGs from class I profiles were significantly enriched in 22 pathways and the most enriched pathway was Rap1 signaling pathway. DEGs from class II profiles were significantly enriched in 17 pathways and the mainly enriched pathway was AMPK signaling pathway. Finally, six selected DEGs from our sequencing results were confirmed by qPCR. Our study provides a comprehensive understanding of the molecular mechanisms during goat skeletal muscle development from fetal to neonatal stages and valuable information for future studies of muscle development in goats. PMID- 28993899 TI - Industrial antifoam agents impair ethanol fermentation and induce stress responses in yeast cells. AB - The Brazilian sugarcane industry constitutes one of the biggest and most efficient ethanol production processes in the world. Brazilian ethanol production utilizes a unique process, which includes cell recycling, acid wash, and non aseptic conditions. Process characteristics, such as extensive CO2 generation, poor quality of raw materials, and frequent contaminations, all lead to excessive foam formation during fermentations, which is treated with antifoam agents (AFA). In this study, we have investigated the impact of industrial AFA treatments on the physiology and transcriptome of the industrial ethanol strain Saccharomyces cerevisiae CAT-1. The investigated AFA included industrially used AFA acquired from Brazilian ethanol plants and commercially available AFA commonly used in the fermentation literature. In batch fermentations, it was shown that industrial AFA compromised growth rates and glucose uptake rates, while commercial AFA had no effect in concentrations relevant for defoaming purposes. Industrial AFA were further tested in laboratory scale simulations of the Brazilian ethanol production process and proved to decrease cell viability compared to the control, and the effects were intensified with increasing AFA concentrations and exposure time. Transcriptome analysis showed that AFA treatments induced additional stress responses in yeast cells compared to the control, shown by an up-regulation of stress-specific genes and a down-regulation of lipid biosynthesis, especially ergosterol. By documenting the detrimental effects associated with chemical AFA, we highlight the importance of developing innocuous systems for foam control in industrial fermentation processes. PMID- 28993900 TI - Outcome of secondary root canal treatment filled with Thermafil: a 5-year follow up of retrospective cohort study. AB - OBJECTIVES: The aim of the present retrospective cohort study was to assess the 5 year outcome and survival of secondary root canal treatments (2 degrees RCT), exploring the influence of pre-, intra-, and post-operative variables. MATERIALS AND METHODS: One hundred thirty-two endodontically retreated teeth were radiographically and clinically re-examined after 5 years. 2 degrees RCT had been performed during a Masters program following standardized protocols and filled with AH Plus/Thermafil (TF). Pre-, intra-, and post-operative data were collected. The 5-year outcome was blindly evaluated and categorized as healed/diseased on the basis of the periapical index. Bivariate analysis and chi square test evaluated the association between outcome and 31 demographic/clinical parameters. Multilevel analysis was performed at both patient and tooth level. Statistical significance was calculated at 5% level. RESULTS: At 5-year evaluation, survival rate was 80% with 7.5% lost for endodontic reasons. Eighty three percent of the teeth were classified as healed. Multilevel analysis identified significant predictors of increased survival: female gender (p = 0.012), absence of a pre-operative metal post (p = 0.017), conservative apical preparation (diameter size < #35) (p = 0.039), teeth restored with a crown (p = 0.009), and final PAI (after 5 years) <= 2 (p = 0.001). Multilevel analysis identified as predictor healing: not being a smoker (p = 0.048) and conservative apical preparation < size #35 (p = 0.037). CONCLUSIONS: Outcome of 2 degrees RCT filled with Thermafil was successful at 5 years, showing a high rate of survived and healed teeth comparable to that reported previously for other obturation techniques. CLINICAL RELEVANCE: Present findings confirm 2 degrees RCT as a valid therapeutic option to retain natural teeth. PMID- 28993901 TI - Collagen gel droplet-embedded culture drug sensitivity test for adjuvant chemotherapy after complete resection of non-small-cell lung cancer. AB - PURPOSE: We conducted a prospective clinical study to individualize adjuvant chemotherapy after complete resection of non-small-cell lung cancer (NSCLC), based on the drug sensitivity test. METHODS: Patients with resectable c-stage IB IIIA NSCLC were registered between 2005 and 2010. We performed the collagen gel droplet-embedded culture drug sensitivity test (CD-DST) on a fresh surgical specimen to assess in vitro chemosensitivity and evaluated the prognostic outcome after adjuvant chemotherapy with carboplatin/paclitaxel based on the CD-DST. RESULTS: Among 92 registered patients, 87 were eligible for inclusion in the analysis. The success rate of CD-DST was 86% and chemosensitivity to carboplatin and/or paclitaxel was evident in 57 (76%) of the 75 patients. Adjuvant chemotherapy was completed in 22 (73%) of 30 patients. The 5-year overall survival rates were 71, 73, and 75% for all, CD-DST success, and chemosensitive patients, respectively. The 5-year disease-free survival and overall survival rates of the chemosensitive patients who completed adjuvant chemotherapy using carboplatin/paclitaxel were 68 and 82%, respectively. The 5-year disease-free survival and overall survival rates of the patients with stage II-IIIA chemosensitive NSCLC were 58 and 75%, respectively. Comparative analyses of the chemosensitive and non-chemosensitive/CD-DST failure groups showed no significant survival difference. CONCLUSIONS: CD-DST can be used to evaluate chemosensitivity after lung cancer surgery; however, its clinical efficacy for assessing individualized treatment remains uncertain. PMID- 28993903 TI - 2017 Awards in the Journal of Plant Research. PMID- 28993902 TI - Cardiac involvement in undifferentiated connective tissue disease at risk for systemic sclerosis (otherwise referred to as very early-early systemic sclerosis): a TDI study. AB - Undifferentiated connective tissue disease at risk for systemic sclerosis (UCTD risk-SSc), otherwise referred to as very early-early SSc, is a condition characterized by Raynaud's phenomenon with serum SSc marker autoantibodies and/or typical capillaroscopic findings and unsatisfying classification criteria for the disease. The aim of the present study was to assess the prevalence of right (RV) or left ventricular (LV) systolic and/or diastolic dysfunction by standard echocardiography and tissue Doppler imaging (TDI). Thirty patients with UCTD-risk SSc (28 female, mean age 47 +/- 13 years, range 21-70) and 30 age- and sex matched controls underwent cardiac assessment by standard echocardiography and TDI. UCTD-risk-SSc patients and controls did not show any difference at standard echocardiography. Despite results falling within the respective normal ranges, TDI pointed out a mild impairment of LV and RV diastolic (E m 15 +/- 4 vs. 19 +/- 5, p = 0.0004; E/E m 6.1 +/- 1.7 vs. 4.8 +/- 1.2, p = 0.001; E t 14 +/- 3 vs. 16 +/- 2, p = 0.02; E t/A t 0.9 +/- 0.4 vs. 1.3 +/- 0.3, p = 0.002; E/E t 3.5 +/- 1.2 vs. 4.2 +/- 0.9, p = 0.02) and systolic function (S m 13 +/- 3 vs. 15 +/- 2 cm/s, p < 0.0003; S t 14 +/- 2 vs. 16 +/- 3 cm/s, p < 0.0001) and increased estimated pulmonary artery wedge pressure (9 +/- 2 vs. 8 +/- 1, p = 0.001) in UCTD-risk-SSc patients as compared to controls. Notably, a statistically significant difference also emerged in the prevalence of TDI detected E'/A't, (71% of UCTD-risk-SSc patients vs. 19% of controls; p < 0.0001). Our study shows that UCTD-risk-SSc patients show a previously unrecognized, mild biventricular systolic and diastolic dysfunction as compared to controls. The pathophysiologic meaning as well the predictive value of developing overt SSc await to be elucidated. PMID- 28993904 TI - Management of radiation-induced mucosal necrosis with photobiomodulation therapy. PMID- 28993905 TI - Large semicircular inverted internal limiting membrane flap in the treatment of macular hole in high myopia. AB - PURPOSE: To describe the technique and surgical outcomes of a modified large semicircular inverted internal limiting membrane (ILM) flap in the management of macular holes (MHs) in patients with high myopia. METHODS: We performed this retrospective study on consecutive patients with MH and high myopia (axial length >= 28 mm),who received vitrectomy, a large semicircular ILM flap 4 discs in diameter to cover the MH, incomplete air-fluid exchange, and SF6 gas tamponade. All of the patients maintained an upright position for 2 h postoperatively, followed by either a face-down or upright position for 1 week. Post-operative visual acuity was measured, and MH status was assessed using spectral-domain optical coherence tomography. RESULTS: Seventeen highly myopic eyes in 16 patients with a mean axial length of 30.49 +/- 0.98 mm and mean age of 62.25 +/- 9.40 years were included in this study, including five eyes with foveoschisis and four eyes with chronic MH, two with myopic choroidal neovascularization, and four with MH-associated retinal detachment. The MHs of all patients were successfully closed after a single operation. All of the patients were followed for at least 6 months. The average visual acuity in logarithm of minimal angle of resolution improved from 1.26 +/- 0.52 preoperatively to 0.69 +/- 0.45 6 months postoperatively (p = 0.01, paired t-test). CONCLUSION: A large semicircular inverted ILM flap can close a myopic MH efficiently without the need for a long term face-down position. PMID- 28993906 TI - Antiangiogenesis and medical therapy failure in intracranial atherosclerosis. AB - Intracranial atherosclerotic disease (ICAD) is one of the most common causes of stroke worldwide and the one with the worst prognosis. In this study, we assessed the hypothesis that the balance of circulating pro- and antiangiogenic factors plays a role in the evolution of the disease and can be used as a potential marker for the disease course and a target for treatment. Seventy-four patients with severe ICAD were enrolled in this prospective observational study, medically optimized, and followed for 6 months. Thirteen pro- and eight antiangiogenic factors were measured in the participants' serum using a sandwich multiplex ELISA. Angiogenic profiles were calculated using principal component analysis. We tested the association between angiogenic profiles and recurring cerebrovascular events despite intensive medical therapy, disability at 6 months after enrollment, and angiographic neovascularization in patients who failed medical treatment and underwent indirect revascularization surgery. There is a strong association between a functionally antiangiogenic profile and recurrent stroke or TIA in patients with ICAD (OR = 7.2, CI 2.4-34.4). Multivariable regression analysis showed that this antiangiogenic profile was also associated with poor functional status after 6 months (p = 0.002), independent from other clinical features such as history of previous stroke, diabetes, and age. In patients who failed medical management and underwent indirect revascularization surgery, high endostatin and angiostatin levels were also associated with low angiographic neovascularization (p = 0.02). The results of this study point to the striking importance of antiangiogenesis as a determinant of ICAD patient prognosis and suggest a possible new target for therapy. PMID- 28993907 TI - [Munich Nomenclature III: classification according to risk : Follow-up for conspicuous squamous findings]. AB - AIM: The present study evaluates the risk of progression of cytologic diagnoses which do not require immediate therapy but do need follow-up. The presented data can contribute to risk-adapted management strategies, according to Munich Nomenclature III. METHODS: Between January 2014 and March 2016, 3396 women were diagnosed as group II-p, IIID1, III-p, IIID2, IVa-p, IVb-p, and V-p and represent the study population. Follow-up information on all subsequent cytologic and histologic findings were collected up to July 2017. For the initial cytologic diagnosis, the cumulative risk of CIN2+ or CIN3+ and the risk for persistent pathologic findings was calculated. RESULTS: The cumulative risk of CIN2+ for initial findings II-p, IIID1, III-p, and IIID2 is calculated as 7.3, 17.1, 46.3, and 62.4%, respectively, after a mean observation period of 24.4, 21.1, 15.6, and 14.3 months. The cumulative risk of CIN3+ (%) is determined as 5.0, 9.3, 37.6, and 45.8. For persistent cytologic diagnoses II-p, IIID1, III-p, and IIID2, the risk of CIN2+ increases significantly after the second result (0 to 3.6, 0.21 to 3.6, 7.2 to 58.3, and 8.1 to 64.7%). Risk of CIN2+ and CIN3+ for group III-p is significantly higher for women <35 years and <30 years compared with women of higher age. There are no significant age-dependent differences for findings II-p, IIID1, and IIID2. CONCLUSIONS: The Munich Nomenclature III classifies cytologic findings according to risk. The diagnostic groups of the Munich Nomenclature III provide a solid basis for a risk-adapted clinical management, if the cytologic history of the individual patient is taken into account. PMID- 28993908 TI - ROS generation and JNK activation contribute to 4-methoxy-TEMPO-induced cytotoxicity, autophagy, and DNA damage in HepG2 cells. AB - 4-Methoxy-TEMPO, a derivative of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), is a stable nitroxide radical and is generally used in organic and pharmaceutical syntheses for the oxidation of alcohols. Previously, we reported the involvement of reactive oxygen species (ROS) and c-Jun N-terminal kinases (JNK) in TEMPO induced apoptosis in mouse L5178Y cells. In this study, we investigated 4-methoxy TEMPO induced toxicity in human HepG2 hepatoma cells and its underlying mechanisms. Treatments with 4-methoxy-TEMPO (0.5-5 mM for 2-6 h) caused oxidative stress as demonstrated by increased intensity of the ROS indicator H2DCF-DA, decreased levels of glutathione. 4-Methoxy-TEMPO treatment also induced DNA damage as characterized by increased levels of DNA tail intensity in the Comet assay, increased phosphorylation of related proteins including gamma-H2A.X, p Chk1, and p-Chk2, and activation of MAPK signaling pathways. In addition, 4 methoxy-TEMPO also induced autophagy as demonstrated by the conversion of LC3B-I to II, decreased level of p62, and the appearance of GFP-LC3B punctae. To investigate the crosstalk between different signaling pathways, pretreatment of HepG2 with N-acetylcysteine, an ROS scavenger, attenuated 4-methoxy-TEMPO-induced DNA damage, suppressed JNK activation, and diminished autophagy induction. Furthermore, inhibiting JNK activation by a JNK-specific inhibitor, SP600125, decreased DNA damage levels induced by 4-methoxy-TEMPO. These results suggest that multiple mechanisms including ROS generation, DNA damage, and MAPK activation contribute to 4-methoxy-TEMPO-induced toxicity. PMID- 28993909 TI - Coexistence of CLCN1 and SCN4A mutations in one family suffering from myotonia. AB - Non-dystrophic myotonias are characterized by clinical overlap making it challenging to establish genotype-phenotype correlations. We report clinical and electrophysiological findings in a girl and her father concomitantly harbouring single heterozygous mutations in SCN4A and CLCN1 genes. Functional characterization of N1297S hNav1.4 mutant was performed by patch clamp. The patients displayed a mild phenotype, mostly resembling a sodium channel myotonia. The CLCN1 c.501C>G (p.F167L) mutation has been already described in recessive pedigrees, whereas the SCN4A c.3890A>G (p.N1297S) variation is novel. Patch clamp experiments showed impairment of fast and slow inactivation of the mutated Nav1.4 sodium channel. The present findings suggest that analysis of both SCN4A and CLCN1 genes should be considered in myotonic patients with atypical clinical and neurophysiological features. PMID- 28993910 TI - Improved process conditions for increasing expression of MHC class II protein from a stable Drosophila S2 cell line. AB - OBJECTIVES: To investigate the effects of operational process conditions on expression of MHC class II protein from a stable Drosophila S2 cell line. RESULTS: When the Drosophila S2 cells were grown in vented orbitally shaken TubeSpin bioreactor 600 containers, cell growth was improved three-fold and the yield of recombinant major histocompatibility (MHC) class II protein (HLA DR12xHis) increased four-fold over the levels observed for the same cells cultivated in roller bottles (RB) without vented caps. Culturing in RB with vented caps while increasing the rotation speed from 6 rpm to 18 rpm also improved cell growth five-fold and protein productivity three-fold which is comparable to the levels observed in the orbitally shaken containers. Protein activity was found to be almost identical between the two vessel systems tested. CONCLUSIONS: Optimized cell culture conditions and a more efficient vessel type can enhance gas transfer and mixing and lead to substantial improvement of recombinant product yields from S2 cells. PMID- 28993911 TI - Identifying the Intersection of Alcohol, Adherence and Sex in HIV Positive Men on ART Treatment in India Using an Adapted Timeline Followback Procedure. AB - People living with HIV (PLHIV) on anti-retroviral treatment (ART) who drink are less adherent and more likely to engage in unprotected sex but the connections among these events are correlational. Using an adapted Timeline Follow-Back (A TLFB) procedure, this paper examines the day by day interface of alcohol, medication adherence and sex to provide a fine grained understanding of how multiple behavioral risks coincide in time and space, explores concordance/discordance of measures with survey data and identifies potential recall bias. Data are drawn from a survey of behavior, knowledge and attitudes, and a 30 day TLFB assessment of multiple risk behaviors adapted for the Indian PLHIV context, administered to 940 alcohol-consuming, HIV positive men on ART at the baseline evaluation stage of a multilevel, multi-centric intervention study. On days participants drank they were significantly more likely to be medication non-adherent and to have unprotected sex. In the first day after their alcohol consuming day, the pattern of nonadherence persisted. Binge and regular drinking days were associated with nonadherence but only binge drinking co-occurred with unprotected sex. Asking about specific "drinking days" improved recall for drinking days and number of drinks consumed. Recall declined for both drinking days and nonadherence from the first week to subsequent weeks but varied randomly for sex risk. There was high concordance and low discordance between A-TLFB drinking and nonadherence but these results were reversed for unprotected sex. Moving beyond simple drinking-adherence correlational analysis, the A-TLFB offers improved recall probes and provides researchers and interventionists with the opportunity to identify types of risky days and tailor behavioral modification to reduce alcohol consumption, nonadherence and risky sex on those days. PMID- 28993912 TI - The utility of magnetic resonance imaging in addition to computed tomography scans in the evaluation of cervical spine injuries: a study of obtunded blunt trauma patients. AB - PURPOSE: Evidence guiding the use of CT and MRI scans in blunt trauma patients who are obtunded remains controversial. This study aims to determine and predict if computed tomography (CT) scans alone can be performed without risking oversight of substantial injuries found on follow-up magnetic resonance imaging (MRI). METHODS: This is a retrospective cohort study of 63 blunt trauma patients with a Glasgow Coma Scale of < 8. Data were collated from electronic medical records and included patient demographics, premorbid mobility, mechanism of injury, suspected level of injury and neurological examination findings. Patients were urgently evaluated using CT scans, followed by non-contrast MRI scans within 48 h of admission. The accuracy of CT scan was evaluated using MRI as a reference. Adjusted multivariable analysis was also performed to identify predictors for findings detected on MRI but not on CT. RESULTS: The mean age of patients was 42.3 years and 90.5% were males. CT scans had a high specificity of 100% and sensitivity of 87.2%. Predictors of MRI abnormalities include females, patients with relatively milder mechanisms of injury, patients with suspected thoracic spine injury, and CT scan findings of facet dislocation and intracranial haemorrhage. There was no predictor for spinal cord oedema. CONCLUSIONS: MRI should be performed in the presence of the aforementioned predictive factors and in the presence of neurological deficits. Otherwise, patients can be treated medically without the fear of missing a substantial cervical injury. PMID- 28993913 TI - Pelvic fractures in the Netherlands: epidemiology, characteristics and risk factors for in-hospital mortality in the older and younger population. AB - PURPOSE: To examine nationwide epidemiology of pelvic fractures in the Netherlands and to compare characteristics and outcome of older versus younger patients as well as predictors for in-hospital mortality. METHODS: Retrospective review of pelvic fracture patients admitted to all Dutch hospitals (2008-2012) utilizing National Trauma Registry. Average annual incidence of (minor and major) pelvic fractures was calculated for the population. Older (>= 65 years) and younger (< 65 years) patients were compared. Multivariate regression analysis was performed to identify independent predictors for in-hospital mortality. RESULTS: Of 11,879 pelvic fracture patients (61.8%, >= 65 years), annual incidence of pelvic fractures in older versus younger population was 57.9 versus 6.4 per 100,000 persons. Older patients had lower ISS (7.1 (SD 6.9) vs 15.4 (SD 13.4)) and less frequently had severe associated injuries (15.6 vs 43.5%), an admission systolic blood pressure (SBP) <= 90 mmHg (1.6 vs 4.1%) or Glasgow Coma Score (GCS) <= 12 (2.0 vs 13.3%) (all, p < 0.01). In-hospital mortality was equal in older and younger patients (5.3 vs 4.8%: p = 0.28). In both subgroups, greatest independent predictors for in-hospital mortality were GCS <= 12, ISS >= 16, and SBP <= 90 mmHg and in all patients age >= 65 (OR 6.59 (5.12-8.48): p < 0.01). CONCLUSION: The annual incidence of (both minor and major) pelvic fractures in the older population was substantially higher than in the younger population. Elderly patients had a disproportionately high in-hospital mortality rate considering they were less severely injured. Among other factors, age was the greatest independent predictor for in-hospital mortality in all pelvic fracture patients. PMID- 28993915 TI - Impact of the New Mental Health Services on Rates of Suicide and Hospitalisations by Attempted Suicide, Psychiatric Problems, and Alcohol Problems in Brazil. AB - A sizeable proportion of all suicides have mental health issues in the background. The association between access to mental health care in the community and decreased suicide rates is inconsistent in the literature. Brazil undertook a major psychiatric reform strengthening psychiatric community-based care. To evaluate the impact of the new Brazilian community mental health care units (CAPS Psychosocial-Community-Centres) on municipal rates of suicide, and hospitalisations by attempted suicide, psychiatric and alcohol problems. We performed robust multivariable negative binomial regression models with fixed effect for panel data from all 5507 Brazilian municipalities. Suicide and hospitalization rates were calculated by sex and standardised by age for each municipality and year from 2008 to 2012. The main variable of interest was municipal CAPS coverage. CAPS municipal coverage was associated with lower suicide rates but this was not statistically significant (RR: 0.981; 95% CI 0.952 1.011). However, increased CAPS coverage was associated with lower hospitalizations for attempted suicide (RR: 0.887; 95% CI 0.841-0.935), psychiatric (RR: 0.841; 95% CI 0.821-0.862), and alcohol problems (RR: 0.882; 95% CI 0.860-0.904). Our results suggest that access to community mental health services seems to reduce hospitalisations due to attempted suicide, psychiatric and alcohol problems but not suicidal rates. Therefore, increased investments in community mental health services in low-middle-income countries might decrease costs associated with potentially avoidable hospitalizations. PMID- 28993914 TI - Operative vectors, anatomic distortion, fluid dynamics and the inherent effects of pneumatic insufflation encountered during transanal total mesorectal excision. AB - BACKGROUND: Transanal total mesorectal excision (taTME) is an altogether different approach to rectal cancer surgery, and the effects of carbon dioxide (CO2) on this dissection remain poorly described. METHODS: This article critically examines the effect of carbon dioxide insufflation and the workspace it creates during the process of taTME. The unique aspects of insulation with this approach are governed by the laws of physics, especially the principles of fluid dynamics, an area that remains poorly described for laparoscopy and not at all described for taTME. RESULTS: A summary of established factors which affect the operative field of the taTME surgeon is delineated and further explored. In addition, new concepts regarding gas delivery, such as insufflation vectors, anatomic distortion, hyper-dissection, and workspace volume rate of change as a function of taTME dissection time, are addressed. Collectively, these factors pose important challenges which increase case complexity and are thus essential for taTME trainers and trainees alike to understand. CONCLUSIONS: Although an invisible gas, CO2 insufflation with taTME produces markedly visible effects which are imposed upon the operative field. This can result in anatomic distortion and misperception of operative planes. Thus, practicing taTME surgeons should be cognizant of these effects. PMID- 28993916 TI - Antimicrobial metabolites from Saraca asoca impairs the membrane transport system and quorum-sensing system in Pseudomonas aeruginosa. AB - This study was conducted to explore the antimicrobial mechanism of metabolites from Saraca asoca (SA1) using differential proteomics and metabolic profile of Pseudomonas aeruginosa after treatment with effective sub-MIC dose of 312 ug/mL. SA1 fraction was found to contain antibacterial metabolites catechol, protocatechuic acid, and epigallocatechin gallate. Proteome analysis revealed 33 differentially expressed proteins after SA1 treatment. Protein network analysis showed that SA1 treatment upregulated the DNA topological and metabolic processes. Furthermore, it revealed that T2SS, cellular component biogenesis, and response to chemical stimuli were inhibited by SA1 treatment, supported by down regulated Na+/H+ antiporter, SdeX, ompK, and trbD proteins. Statistical analysis of mass data revealed the altered level of 20 metabolites includes HSLs, PQS, rhamnolipid, and pyocyanin. Proteome and metabolome results showed that treatment impaired cell membrane functions and quorum-sensing system. It was further confirmed by increased MDA (3.95 fold), and rhamnolipids (4.3 fold) production and, therefore, oxidative stress (36.9%) after SA1 treatment. PMID- 28993917 TI - Cognitive test batteries in animal cognition research: evaluating the past, present and future of comparative psychometrics. AB - For the past two decades, behavioural ecologists have documented consistent individual differences in behavioural traits within species and found evidence for animal "personality". It is only relatively recently, however, that increasing numbers of researchers have begun to investigate individual differences in cognitive ability within species. It has been suggested that cognitive test batteries may provide an ideal tool for this growing research endeavour. In fact, cognitive test batteries have now been used to examine the causes, consequences and underlying structure of cognitive performance within and between many species. In this review, we document the existing attempts to develop cognitive test batteries for non-human animals and review the claims that these studies have made in terms of the structure and evolution of cognition. We argue that our current test battery methods could be improved on multiple fronts, from the design of tasks, to the domains targeted and the species tested. Refining and optimising test battery design will provide many benefits. In future, we envisage that well-designed cognitive test batteries may provide answers to a range of exciting questions, including giving us greater insight into the evolution and structure of cognition. PMID- 28993918 TI - A new albumin-depletion strategy improves proteomic research of gingival crevicular fluid from periodontitis patients. AB - OBJECTIVES: Gingival crevicular fluid (GCF), the inflammatory infiltrate within the crevicular sulcus, is of great importance for diverse processes in the oral cavity and has a high impact in oral sciences. It is assumed to serve as a source of biomarkers for systemic or periodontal diseases and mediators of orthodontic tooth movement. In order to characterize the protein content of the GCF in an unbiased and complete approach, we employed mass spectrometry (MS), which allows not only the identification, but also the quantification of these proteins. In samples obtained from patients suffering from periodontitis, this method is often limited due to the presence of highly abundant serum albumin deriving from serum. The aim of this investigation was to employ a protein precipitation procedure for the efficient depletion of serum albumin from GCF samples. MATERIALS AND METHODS: GFC samples collected from five adult periodontitis patients were fractionated by trichloroacetic acid/acetone precipitation and the resulting soluble and pelleted fractions were analyzed by SDS-PAGE and high-resolution mass spectrometry. RESULTS: Trichloroacetic acid/acetone precipitation was successfully employed as a protein precipitation procedure for the efficient depletion of serum albumin from GCF samples. Careful analysis revealed that the precipitation step reduced the serum albumin content efficiently, and increased subsequent protein identifications by 32%. Three hundred seventeen proteins could only be identified with this new approach. CONCLUSION: The increased coverage of the GCF proteome will help improve our understanding of molecular mechanisms in the periodontium during pathogenesis of periodontitis. CLINICAL RELEVANCE: Our new albumin depletion strategy combined with high-resolution mass spectrometry can be used to effectively monitor the molecular signals of the periodontium. PMID- 28993919 TI - Deinococcus petrolearius sp. nov. isolated from crude oil recovery water in China. AB - A Gram-stain positive, non-motile, spherical, red-pigmented and facultatively anaerobic bacterium, designated strain 6.1T, was isolated from a crude oil recovery water sample from the Huabei oil field in China. The novel strain exhibited tolerance of UV irradiation (> 1000 J m-2). Based on 16S rRNA gene sequence comparisons, strain 6.1T shows high similarity to Deinococcus citri DSM 24791T (98.1%) and Deinococcus gobiensis I-0T (97.8%), with less than 93.5% similarity to other closely related taxa. The major cellular fatty acids were identified as summed feature 3 (C16:1 omega7c and/or iso-C15:0 2-OH), followed by iso-C17:1 omega9c and C16:0. The polar lipid profile was found to contain phospholipids, glycolipids, phosphoglycolipids and aminophospholipids. The predominant respiratory quinone was identified as MK-8. The DNA G + C content was determined to be 68.3 mol %. DNA-DNA hybridization between strain 6.1T and D. citri DSM 24791T was 45.6 +/- 7.1% and with D. gobiensis I-OT was 36.6 +/- 4.7%. On the basis of phylogenetic, chemotaxonomic and phenotypic data, we conclude strain 6.1T represents a novel species of the genus Deinococcus, for which we propose the name Deinococcus petrolearius sp. nov. The type strain is 6.1T (= CGMCC 1.15053T = KCTC 33744T). PMID- 28993920 TI - Laparoscopic lymph node dissection around the inferior mesenteric artery for left sided colon and rectal cancer. AB - Lymph node dissection is a critical part of surgery for colorectal cancer. Japanese D3 and complete mesocolic excision are two unique principles for lymph node dissection in colorectal cancer. Laparoscopic surgery magnifies the targets and provides insight about the micro-anatomy through high-quality, high definition imaging, which benefits the surgeon. Although laparoscopic colorectal resection is feasible, there is no universal procedure. We describe in detail the anatomy viewed during lymph node dissection around the inferior mesenteric artery. Visual recognition of two folds on both sides of Landzert's fossa is the critical first step, as recognizing these structures allows laparoscopic procedures to be performed safely. Our findings suggest that this procedure is feasible and effective for the surgical treatment of patients with left-sided colon or rectal cancer. PMID- 28993921 TI - [Nanna Svartz (1890-1986) : The first female professor of medicine in Sweden]. AB - Nanna Svartz was a charismatic character who played a significant role in Swedish medicine in the mid-twentieth century. As one of five brothers and sisters, she escaped an early death from tuberculosis. She reached 96 years of age. Her diligence and sense of duty were legendary, along with her ambition to fully prove herself as "the first female professor". She inherited a certain insecurity from her father that led to her difficulty in taking criticism. Despite extensive academic obligations, she worked as a treating doctor for 55 years and always took her time with her patients, especially if they held important public positions. Nanna was honoured several times in her lifetime. Among others, she was a member of the Leopoldina, the National Academy of Germany, and received many honorary doctorates, for example, from Rockefeller College (USA) and the Abo University (Turku, Finland). She was an honorary member of over 40 scientific societies. Underneath the new auditorium in the Karolinska Institute, a restaurant and a street in her home town of Vasteras bear her name. An annual international Nanna Svartz Lecture is held by the Swedish Society for Rheumatology, and a Nanna Svartz Prize is awarded annually to a deserving young Swedish rheumatologist. PMID- 28993922 TI - 100 kGy gamma-affected microbial communities within the ancient Arctic permafrost under simulated Martian conditions. AB - This research aimed to investigate the viability and biodiversity of microbial communities within ancient Arctic permafrost after exposure to a gamma-radiation dose of 100 kGy at low temperature (- 50 degrees C), low pressure (1 Torr) and dehydration conditions. The main objective was to assess the possibility for long term survival of Earth-bound microorganisms in the subsurface of Martian regolith or inside small space bodies at constant absorption and accumulation of the gamma radiation dose. Investigated microbial communities had shown high resistance to a simulated Martian environment. After irradiation the total count of prokaryotic cells and number of metabolically active bacterial cells remained at the control level, while the number of bacterial CFUs decreased by 2 orders of magnitude, and the number of metabolically active cells of archaea decreased threefold. Besides, the abundance of culturable bacteria after irradiation was kept at a high level: not less than 3.7 * 105 cells/g. Potential metabolic activity of irradiated microbial communities in general were higher than in the control sample. A fairly high biodiversity of bacteria was detected in the exposed sample of permafrost, although the microbial community structure underwent significant changes after irradiation. In particular, actinobacteria populations of the genus Arthrobacter, which was not revealed in the control samples, became predominant in bacterial communities following the exposure. The results of the study testify that long term preservation of microbial life inside Martian permafrost is possible. The data obtained can also be evaluated from the perspective of the potential for discovering viable Earth-bound microorganisms on other objects in the Solar system and inside of small bodies in outer space. PMID- 28993923 TI - An optimal design for the study of palliative sedation-making somewhat better pictures. PMID- 28993924 TI - Effects of Acetylcholine on beta-Amyloid-Induced cPLA2 Activation in the TB Neuroectodermal Cell Line: Implications for the Pathogenesis of Alzheimer's Disease. AB - The role of beta-amyloid (Abeta) in the pathogenesis of Alzheimer's disease (AD) is still considered crucial. The state of Abeta aggregation is critical in promoting neuronal loss and neuronal function impairment. Recently, we demonstrated that Acetylcholine (ACh) is neuroprotective against the toxic effects of Abeta in the cholinergic LAN-2 cells. In biophysical experiments, ACh promotes the soluble Abeta peptide conformation rather than the aggregation-prone beta-sheet conformation. In order to better understand the biological role of ACh in AD, we studied the effect of Abeta on the phosphorylation of the cytosolic phospholipase A2 (cPLA2) in the TB neuroectodermal cell line, which differentiates toward a neuronal phenotype when cultured in the presence of retinoic acid (RA). We chose the phosphorylated form of cPLA2 (Ser505, Phospho cPLA2) as a biomarker to test the influence of ACh on the effects of Abeta in both undifferentiated and RA-differentiated TB cells. Our results show that TB cells are responsive to Abeta. Moreover, in undifferentiated cells 1 h treatment with Abeta induces a 2.5-fold increase of the Phospho-cPLA2 level compared to the control after 24 h in vitro, while no significant difference is observed between Abeta-treated and non-treated cells after 4 and 7 days in vitro. The RA differentiated cells are not sensitive to Abeta. In TB cell line ACh is able to blunt the effects of Abeta. The ability of ACh to protect non-cholinergic cells against Abeta reinforces the hypothesis that, in addition to its role in cholinergic transmission, ACh could also act as a neuroprotective agent. PMID- 28993925 TI - Microhabitat use of the western black-crested gibbon inhabiting an isolated forest fragment in southern Yunnan, China: implications for conservation of an endangered species. AB - Due to the synergistic effects of hunting and habitat loss, populations of the western black-crested gibbon are currently restricted to isolated forest fragments. The home range use of this species in fragmented forests is presumptively related to spatial, food and vegetation attributes, as in other primates. We examined the distributions of different food resources, the structure of the vegetation (tree density, DBH, and height), and the microhabitat use of one gibbon group in an isolated and disturbed forest at Bajiaohe in southern Yunnan, China. The results indicated that the gibbons used the edge habitat frequently, which was subject to more anthropogenic disturbance than the interior forest, and they appeared to adapt to discontinuous canopy cover by using bamboo and tsaoko plants for travel. The group also modified its diet in response to fluctuations in food availability and the local flora. However, the gibbons intensively used areas with high tree fruit availability across the two study periods. It is suggested that the microhabitat use by the group was mostly affected by the distribution of particular food resources and canopy gaps caused by selective logging. Protecting the current distribution area and planting native important food species to boost habitat quality and connectivity should be considered as part of conservation plans of the western black crested gibbon living in limited areas. PMID- 28993926 TI - Effects of dust on forest tree health in Zagros oak forests. AB - Dust is one of the most devastating factors for the environment threatening all animal and plant species. In many regions, the ecological and economic impact of microdust on scarce species is critical. In the western region of Iran, the Zagros forests have been exposed to dust storms for many years. In this study, the effect of dust on oak trees, the most important trees of Zagros forests, is investigated. For this purpose, 3-year-old seedlings of three species of oak trees under natural conditions were exposed to dust during spring and summer months. Seedlings were divided into two groups; one group was assigned as dust treatment and the other as control that the control group washed regularly to remove dust. Anatomical characteristics of leaves and dust deposits on leaves during the study period were examined by scanning electron microscope (SEM). The rate of photosynthesis and gas exchange in control and treated plants was examined by IRGA, LCI. SEM images showed that stomata structure, trichome density, and epicuticular waxes of leaves are different in all three species. This difference in micromorphology of species influences the effects of dust deposited on the leaves. A comparison of leaf species images in control and dust treatment showed that in dust treatment the percentage of stomata blocked by dust in three species (per unit area) of Quercus infectoria, Q. libni, and Q. brantii were 61/6, 48/4, and 38/1%, respectively. The results of leaf gas exchange investigation indicated that stomatal occlusion by dust had a negative impact on the examined parameters of three oak species (P <= 0.01). Thus, gas exchange and photosynthetic rates of the treated species were significantly reduced. The results of both parts of the study showed the vulnerability of the three species to dust as Q. infectoria > Q. libni > Q. brantii. Therefore, based on these findings, dust can disrupt the physiological activities of the studied species and the continuation of the exposure to dust will accelerate the process of destruction of these forests. PMID- 28993927 TI - Rhodium (II) complex with 2-benzoylpyridine, a novel potential chemotherapeutic drug, induces cell cycle arrest and apoptosis in HepG2 cells. AB - Rhodium (II) complex with 2-benzoylpyridine (Rh(L)2Cl2) is a new, synthetic, active metal-complex, which is produced by the reaction of 2-benzoylpyridine (L) with rhodium chloride hydrate (RhCl3.nH2O). The crystal structure was determined by X-ray diffraction which is mono-nuclear. In order to explore the biological properties of the novel complex, a series of studies were performed. The results showed that Rh(L)2Cl2 had the anti-tumor activity in HepG2 and other cell lines and has been shown to induce G1 cell cycle arrest and apoptosis in HepG2 cells. The anti-cancer effect of Rh(L)2Cl2 is regulated by increased expression of caspase-3 and PARP via the mitochondrial and the death receptor pathways. Bcl-2 family proteins might play an important role in the Rh(L)2Cl2-induced changes in these two pathways. Further studies indicated that Rh(L)2Cl2 increased the level of reactive oxygen species (ROS), but that Rh(L)2Cl2-induced apoptosis was ROS independent. In conclusion, Rh(L)2Cl2 is a potential new anti-tumor drug, which induces HepG2 cell death via the mitochondrial and death receptor pathways and has no obvious toxicity to normal liver cell. PMID- 28993928 TI - TvZNF1 is a C2H2 zinc finger protein of Trichomonas vaginalis. AB - The zinc fingers proteins (ZNF) are the largest family of DNA binding proteins and can act as transcriptional factors in eukaryotes. ZNF are implicated in activation in response to environmental stimulus by biometals such as Zn2+. Many of these proteins have the classical C2H2 zinc finger motifs (C2H2-ZNFm) of approximately 30 amino acids, where a Zn2+ ion is coordinated by two cysteine and two histidine residues. Trichomonas vaginalis is a protozoan parasite than responds to environmental changes including Zn2+. Until now has not been described any ZNF that could be involved in the regulation of genic expression of T. vaginalis. Here, we characterized in silico and experimentally an annoted ZNF (TvZNF1) from T. vaginalis and isolated the gene, tvznf1 encoding it. TvZNF1 have eight C2H2-ZNFm with residues that maybe involved in the structural stability of DNA binding motifs. In this work we confirmed the Zn2+ upregulation expression of tvznf1 gene. Recombinant TvZNF1 was able to bind to specific DNA sequences according to EMSA assay. Additionally, we demonstrated that recombinant TvZNF1 bind to MRE signature in vitro, which strongly suggests its role in transcriptional regulation, similar to the one observed for mammalian MTF-1. This result suggested a conserved mechanism of genic regulation mediated by ZNFs in T. vaginalis. PMID- 28993929 TI - Exploring Provider Use of a Digital Implementation Support System for School Mental Health: A Pilot Study. AB - This pilot study explored provider use of an online system, Centervention, to support the delivery of empirically supported school-based mental health interventions (ESIs); and associations between components of this system [resources, training, technical assistance (TA), feedback loops], implementation indicators, and student outcomes. Multilevel modeling data were collected from 39 providers implementing ESIs with 758 students. Training, TA, and progress monitoring predicted ESI adherence, and perceived value of resources and TA influenced student responsiveness. Greater adherence was predictive of better socio-emotional outcomes. Interviews with 15 providers illuminated how they used these four Centervention support strategies. Implications for digital implementation support research are discussed. PMID- 28993931 TI - Irreversible electroporation in the eradication of rabbit VX2 cervical tumors. AB - The aim of this study was to evaluate the effects of irreversible electroporation (IRE) on the eradication of rabbit VX2 cervical tumors. A VX2 cervical cancer model was first made in 20 New Zealand rabbits. IRE ablation was performed for the cervical cancers of 15 rabbits when the diameter of the tumor was about 1.0 1.5 cm. The control group (n = 5) did not receive IRE ablation. The gross pathology, ultrasound, computed tomography, hematoxylin and eosin, terminal deoxynucleotidyl transferase dUTP nick end labeling assay, and proliferating cell nuclear antigen immunohistochemical staining were performed to evaluate the efficacy of IRE on cervical cancer. All the rabbits tolerated the IRE ablation without serious complications. The tumors treated by IRE slightly increased in size during the first two days, but decreased gradually. IRE caused tumor cell death efficiently, mainly through cell apoptosis; however, it did not induce complete tumor ablation in our study. The results suggested that IRE could eradicate rabbit VX2 cervical tumors efficiently. However, the optimal IRE parameters remain to be determined. PMID- 28993930 TI - In search of a standard when analyzing medication adherence in patients with heart failure using claims data: a systematic review. AB - To determine and address medication non-adherence is important and may improve patient outcomes. Our aim was to perform a systematic review on the operationalization of adherence measures in patients with heart failure using claims data. We searched the MEDLINE, EMBASE, and Cochrane databases. A quality check of the full-text articles was performed using the Quality in Prognosis Studies tool. We included 28 studies. Eleven studies used the medication possession ratio, 15 the proportion of days covered, and six studies used own methods to calculate medication adherence. Almost all studies used an observation period of 1 year. Twenty-one studies considered angiotensin converting enzyme inhibitors or angiotensin receptor antagonists, 17 beta-blockers, 11 diuretics, eight mineralocorticoid receptor antagonists, six digitalis-glycosides, and six statins. Eight studies looked at single substance classes; 18 studies analyzed more than one drug class. Different assumptions for the dosage were used. In seven studies, switching within therapeutic classes was allowed. Three studies allowed stockpiling, nine studies censored hospital stays, and four studies censored death. Seventeen studies dichotomized the results, applying the cutoff >= 0.8 to define a patient as adherent. Eight studies analyzed adherence as a continuous value. The reporting quality of the methodology applied varied widely between studies. A gold standard is currently not available for the quantification of medication adherence in patients with chronic heart failure via claims data. To assess the methodology, the following parameters should be described: method of measurements, observation period, substances, dosing, switches, stockpiling, truncations, statistical analysis, and cutoff for adherence. PMID- 28993932 TI - Genome-wide identification of Cd-responsive NRAMP transporter genes and analyzing expression of NRAMP 1 mediated by miR167 in Brassica napus. AB - In plants, metal transporters are responsible for metal uptake, translocation and homeostasis. These metals include essential nutrients such as zinc (Zn) and manganese (Mn) or non-essential metals like cadmium (Cd) and lead (Pb). Although a few metal transporters have been well characterized in model plants, little is known about their functionality in rapeseed (Brassica napus). In the study, 22 NRAMP transporter genes from B. napus genome were identified and annotated using bioinformatics and high-throughput RNA-sequencing (RNA-seq). Based on the sequence identity, these NRAMP transporters can be classified into 6 subfamilies. RNA-seq analysis revealed that 19 NRAMP transporters were detected and some of the genes were well confirmed by qRT-PCR. Ten NRAMP transporters (45.5%, 10/22) were found to be differentially expressed (> 2 fold change, p < 0.05) under Cd exposure. As an example, we specified expression of BnNRAMP1b under Cd exposure. BnNRAMP1b is a constitutive gene expressing throughout all development stages including seedlings, vegetative tissue, flowers and siliques. Expression of BnNRAMP1b can be strongly induced in seedlings exposed to 80, 160 and 240 MUM Cd. To define whether BnNRAMP1b was specific for Cd transport, a yeast (wild-type, BY4741) system with its mutants (ycf1, zrc1, and smf1) defective in transport activity of Cd, Zn and Mn, respectively were tested. Compared to empty vectors (pYES2), cells carrying BnNRAMP1b can rescue the transport functions. As a consequence, excess Cd, Zn and Mn were taken in the cells, which led to metal toxicity, suggesting that BnNRAMP1b is responsible for transport of these metals in B. napus. Using our previously created degradome datasets, we found that BnNRAMP1b could be cleaved by miR167, suggesting that BnNRAMP1b is a target of miR167 in B. napus. The contrasting expression pattern of BnNRAMP1b and miR167 under Cd stress supported the post-transcriptional regulation of BnNRAMP1b by miR167. PMID- 28993933 TI - Gamma-Glutamyltransferase and Future Risk of Pneumonia: A Long-Term Prospective Cohort Study. AB - Serum gamma-glutamyltransferase (GGT) has been linked with the risk of adverse health outcomes. We aimed to assess the prospective association of GGT activity with pneumonia risk. Serum GGT was measured at baseline in 2400 middle-aged men. Within-person variability in GGT values was corrected for using data from repeat measurements. During a median follow-up of 25.3 years, 409 pneumonia cases were recorded. The age-adjusted regression dilution ratio of GGT was 0.68 (95% CI 0.63 0.73). Gamma-glutamyltransferase was approximately log-linearly associated with pneumonia risk. In analysis adjusted for several major pneumonia risk factors, the hazard ratio (95% CI) for pneumonia per 1 standard deviation increase in GGT was 1.14 (1.02-1.28). The association was however attenuated on additional adjustment for high-sensitivity C-reactive protein (hsCRP) 1.08 (0.96-1.22). There is an approximately log-linear positive association between GGT activity and future risk of pneumonia in a middle-aged male population, which is partly dependent on hsCRP. PMID- 28993934 TI - Successful nuclear DNA profiling of rootless hair shafts: a novel approach. AB - Historically, rootless hair shaft samples submitted to a forensic laboratory for DNA analysis are reserved for mitochondrial DNA (mtDNA) analysis due to the presence of highly degraded as well as insufficient amounts of nuclear DNA. Although mtDNA has been very successful in obtaining results from rootless hair, this system has its limitations, namely, it is a lineage marker that cannot differentiate between maternally related genotypes. Given the high incidence of hairs as forensic evidence, there is a need for the use of a nuclear DNA test system capable of producing reliable results for hair shaft forensic evidence. This study reports the utilization of an enhanced DNA extraction methodology for hairs, in combination with a recently developed novel, nuclear DNA typing assay, InnoTyper(r) 21, to improve the success rate for obtaining informative results from highly compromised, degraded, and trace forensic samples such as rootless hair shafts. The InnoTyper 21 kit is a small amplicon retrotransposon marker typing system compatible with currently used capillary electrophoresis platforms. This system contains 20 Alu element markers, ranging in size from 60 to 125 bp, making the assay highly sensitive for extremely degraded forensic samples and thus enabling recovery of nuclear DNA profiles from samples that would otherwise require mtDNA sequencing. A subset of samples was also tested with the GlobalFiler kit with less success due to the larger amplicon sizes in comparison with InnoTyper 21. Results were variable but very promising, with approximately 40% of the total number of hairs tested producing interpretable nuclear DNA profiles with InnoTyper 21. These results demonstrate the ability of the utilized methodologies to produce nuclear DNA results with high statistical power from rootless hair shafts. PMID- 28993935 TI - Treatment outcome in patients with clinically defined carpal tunnel syndrome but normal electrodiagnostic test results: a randomized controlled trial. AB - Little is known about treatment effect of carpal tunnel release in patients with clinically defined carpal tunnel syndrome (CTS), but normal electrodiagnostic test results (EDX). The aim of this study was to determine whether this category of patients will benefit from surgical treatment. 57 patients with clinically defined CTS and normal EDX were randomized for surgical treatment (n = 39) or non surgical treatment (n = 18). A six-point scale for perceived improvement as well as the Boston Carpal Tunnel Questionnaire was completed at baseline and at follow up after 6 months. A significant improvement of complaints was reported by 70.0% of the surgically treated patients and 39.4% reported full recovery 6 months after surgery. Furthermore, both Functional Status Score and Symptom Severity Score improved significantly more in the surgically treated group (p = 0.036 and p < 0.001, respectively). This study demonstrates that most patients with clinically defined CTS and normal EDX results will benefit from carpal tunnel release. Therefore, this group of CTS patients must not a priori be refrained from surgery. PMID- 28993936 TI - The Influence of Body Composition on Pulmonary Rehabilitation Outcomes in Chronic Obstructive Pulmonary Disease Patients. AB - INTRODUCTION: Alterations in body composition are commonly present in chronic obstructive pulmonary disease (COPD). The hypothesis of this study is that COPD patients would achieve clinical benefits after pulmonary rehabilitation (PR) independent of muscle mass depletion or body weight. METHODS: We conducted a retrospective cohort study using single-frequency bioelectrical impedance analysis (BIA) for assessment of fat-free mass (FFM) depletion (muscle depletion). Patients were stratified into three categories based on (1) obesity BMI >= 30 kg/m2, (2) non-obesity BMI < 30 kg/m2, and (3) combined cachexia (BMI < 21 kg/m2 and FFM index < 16 kg/m2) and muscle atrophy (BMI >= 21 kg/m2 and FFMI < 16 kg/m2). PR outcomes were defined as the improvement in exercise capacity (maximal exercise capacity, 6-min walk, constant workload cycle exercise duration) and quality of life determined by Chronic Respiratory Questionnaire after PR. RESULTS: We studied 72 patients with available FFM measured by BIA. Patients were predominantly elderly man (N = 71; 98%), with a mean age of 72 years with COPD GOLD stage I-IV. The groups were balanced in terms of age, comorbidities, baseline FEV1, exercise capacity, and quality of life. The absolute changes in patients with muscle depletion or obesity compared to those without muscle depletion or obesity were not statistically different as was the percentage of patients reaching the minimal clinically important difference (MCID) after PR. CONCLUSION: A comprehensive PR program in COPD patients improved exercise tolerance and quality of life independent of muscle mass depletion or obesity. Similarly, muscle depletion or obesity had no effect on the percentage of patients achieving the MCID for measures of quality of life and exercise tolerance after PR. PMID- 28993938 TI - I Think We're Alone Now: Solitary Social Behaviors in Adolescents with Autism Spectrum Disorder. AB - Research into emotional responsiveness in Autism Spectrum Disorder (ASD) has yielded mixed findings. Some studies report uniform, flat and emotionless expressions in ASD; others describe highly variable expressions that are as or even more intense than those of typically developing (TD) individuals. Variability in findings is likely due to differences in study design: some studies have examined posed (i.e., not spontaneous expressions) and others have examined spontaneous expressions in social contexts, during which individuals with ASD-by nature of the disorder-are likely to behave differently than their TD peers. To determine whether (and how) spontaneous facial expressions and other emotional responses are different from TD individuals, we video-recorded the spontaneous responses of children and adolescents with and without ASD (between the ages of 10 and 17 years) as they watched emotionally evocative videos in a non-social context. Researchers coded facial expressions for intensity, and noted the presence of laughter and other responsive vocalizations. Adolescents with ASD displayed more intense, frequent and varied spontaneous facial expressions than their TD peers. They also produced significantly more emotional vocalizations, including laughter. Individuals with ASD may display their emotions more frequently and more intensely than TD individuals when they are unencumbered by social pressure. Differences in the interpretation of the social setting and/or understanding of emotional display rules may also contribute to differences in emotional behaviors between groups. PMID- 28993937 TI - Cytogenetic abnormalities of the descendants of permanent residents of heavily contaminated East Kazakhstan. AB - More than 400 nuclear explosion tests were conducted at the Semipalatinsk Nuclear Test Site (SNTS) and significant radioactive substances were released. The long term consequences of the activities at the SNTS and the appearance of any hereditary effects remain insufficiently studied about 25 years after the test site was closed. The population living in villages near the SNTS are considered to have been heavily exposed to external and internal radiation. This study aims to perform an assessment and comprehensive cytogenetic analysis of the inhabitants living near the SNTS, and their first-(F1) and second-(F2) generation children. Residents of the East Kazakhstan region living in the area covered by the former SNTS were included in the study. To evaluate the hereditary effects of nuclear testing, comprehensive chromosome analyses were performed in lymphocytes using conventional Giemsa and fluorescent in situ hybridization methods in 115 F1 and F2 descendants in the villages of Dolon and Sarzhal, which were heavily contaminated. The parents of the subjects had permanently lived in the villages. A higher number of stable-type chromosome aberrations such as translocations was found in these residents than in 80 residents of the control area, Kokpecty, which indicates the possibility that radiation had biological effects on the exposed subjects. PMID- 28993939 TI - Treatment of sphenopalatine artery bleeding. PMID- 28993940 TI - A Randomized Crossover Study Evaluating the Use and Acceptability of the SILCS Diaphragm Compared to Vaginal Applicators for Vaginal Gel Delivery. AB - INTRODUCTION: This study aimed to assess acceptability and preferences for the SILCS diaphragm for vaginal gel delivery compared to a prefilled applicator. METHODS: A randomized crossover study among 115 women in South Africa, using both methods during five sex acts. RESULTS: We found no significant differences in acceptability between the two products. Experience of gel leakage after sex was greater when inserted via applicator. More women were interested in SILCS/gel for multipurpose protection (68%) than in either SILCS alone (17%) or microbicide gel alone (14%). CONCLUSIONS: A SILCS gel delivery system for multipurpose prevention seems feasible and acceptable. PMID- 28993941 TI - IL-8 Is Involved in Estrogen-Related Receptor alpha-Regulated Proliferation and Migration of Colorectal Cancer Cells. AB - BACKGROUND AND AIMS: Studies revealed that estrogenic signals were involved in the development of colorectal cancer (CRC), while the roles of estrogen related receptor (ERR) on the progression of CRC have not been well illustrated. Its roles on the development of CRC were investigated. METHODS: The expression of ERRalpha/beta/gamma in CRC cells were measured. The effects of ERRalpha on cell proliferation, migration and expression of cytokines were investigated accordingly. RESULTS: Our data revealed that the expression of ERRalpha, while not ERRbeta or ERRgamma, was significantly increased in CRC cells and clinical CRC tissues. Both the inverse agonist of ERRalpha (XCT-790) and si-ERRalpha can inhibit the proliferation of CRC cells. XCT-790 treatment can also suppress the wound healing and in vitro migration of CRC cells. Cytokine assays showed that XCT-790 can significantly decrease the expression of interleukin-8 (IL-8), while not IL-4, IL-6, IL-8, IL-9, IL-10, IL-18, IFN-gamma, or TGF-beta, in CRC cells. Over expression of ERRalpha increased the expression of IL-8. Luciferase assay showed XCT-790 decreased the promoter activity of IL-8. XCT-790 can increase the decay of IL-8 mRNA in SW480 cells. The recombinant IL-8 (rIL-8) can rescue XCT 790 induced suppression of proliferation and migration of CRC cells. XCT-790 can decrease the phosphorylation of ERK1/2 and STAT3, two downstream signal molecules of IL-8, in CRC cells. While rIL-8 can markedly attenuate XCT-790 induced dephosphorylation of ERK1/2 and STAT3. CONCLUSION: Our data showed that ERRalpha can trigger the proliferation and migration of CRC cells via up regulation of IL 8. Therefor targeted inhibition of ERRalpha/IL-8 might be a potential approach for CRC treatment and drug development. PMID- 28993942 TI - Cannabinoid receptor 2 as a novel target for promotion of renal cell carcinoma prognosis and progression. AB - PURPOSE: Renal cell carcinoma (RCC) is the most common malignancy of urogenital system, and patients with RCC may face a poor prognosis. However, limited curable therapeutic options are currently available. The aim of this study is to investigate the role of Cannabinoid receptor 2 (CB2) in RCC progression. METHODS: Immunohistochemistry was to investigate the expression pattern of CB2 in 418 RCC tissues and explore its prognostic function in RCC patients. Furthermore, the role of used CB2 si-RNA knockdown and inhibited by AM630, a CB2 inverse agonist, on cell proliferation, migration, and cell cycle of RCC cell lines in vitro was also investigated. RESULTS: We observed that CB2 was up-regulated in RCC tissues, and presented as an independent prognostic factor for overall survival of RCC patients and higher CB2 expression tends to have poor clinical outcomes in survival analyses. Moreover, we also observed that CB2, incorporated with pN stage, pathological grade, and recurrence or distant metastasis after surgery, could obviously enhance their prognostic accuracy in a predictive nomogram analysis. In addition, knockdown or inhibition by AM630 for the expression of CB2 in vitro could significantly decreased cell proliferation and migration, and obviously induced cell cycle arrest in G2/M of RCC cells. CONCLUSIONS: CB2 expression is functionally related to cellular proliferation, migration, and cell cycle of RCC cells. Our data suggest that CB2 might be a potential therapeutic target for RCC. PMID- 28993943 TI - The female advantage in natural populations of gynodioecious Plantago coronopus: seed quantity vs. offspring quality. AB - In gynodioecious plant species, females can only persist when they have a reproductive advantage in comparison with hermaphrodites. However, several studies have shown that females do not necessarily produce more seeds than hermaphrodites, since seed production can be affected by population characteristics, such as female frequency or population size. The aim of this study was to quantify the female advantage across a large number of natural populations, examine its relationship with population sex ratio and size, and to assess the role of competition on the magnitude of the female advantage. We sampled 27 populations of Plantago coronopus (nuclear-cytoplasmic gynodioecy) along the Belgian and Dutch coast. In each population, we estimated population sex ratio and size, and assessed seed production per flower and seed production per plant. Subsequently, germination, growth, and competition experiments were performed in the greenhouse to determine the female advantage regarding offspring quality. Females produced fewer seeds per plant than hermaphrodites (FA = 0.90), and seed production was negatively related to female frequency. Since both sex morphs were equally affected by pollen availability, the female advantage was not related to population sex ratio. On the other hand, offspring of females showed higher germination and growth rates, resulting in higher competitive abilities when seeds of a female and a hermaphrodite were grown together. Overall, these results indicate that differences in competitive abilities between the offspring of females and hermaphrodites may have contributed to the maintenance of females in relatively high frequencies in populations of this short-lived gynodioecious plant species. PMID- 28993944 TI - Palliative care content on cancer center websites. AB - PURPOSE: Professional guidelines recommend that palliative care begin early in advanced cancer management, yet integration of palliative and cancer care remains suboptimal. Cancer centers may miss opportunities to provide palliative care information online. In this study, we described the palliative care content on cancer center websites. METHODS: We conducted a systematic content analysis of 62 National Cancer Institute- (NCI) designated cancer center websites. We assessed the content of center homepages and analyzed search results using the terms palliative care, supportive care, and hospice. For palliative and supportive care webpages, we assessed services offered and language used to describe care. Two researchers analyzed all websites using a standardized coding manual. Kappa values ranged from 0.78 to 1. RESULTS: NCI-designated cancer center homepages presented information about cancer-directed therapy (61%) more frequently than palliative care (5%). Ten percent of cancer centers had no webpage with palliative care information for patients. Among centers with information for patients, the majority (96%) defined palliative or supportive care, but 30% did not discuss delivery of palliative care alongside curative treatment, and 14% did not mention provision of care early in the disease process. CONCLUSIONS: Cancer center homepages rarely mention palliative care services. While the majority of centers have webpages with palliative care content, they sometimes omit information about early use of care. Improving accessibility of palliative care information and increasing emphasis on early provision of services may improve integration of palliative and cancer care. PMID- 28993945 TI - Drug-eluting bead transarterial chemoembolization in the treatment for unresectable soft tissue sarcoma refractory to systemic chemotherapy: a preliminary evaluation of efficacy and safety. AB - PURPOSE: To preliminarily evaluate the clinical efficacy and safety of drug eluting bead transarterial chemoembolization (DEB-TACE) for unresectable soft tissue sarcoma refractory to systemic chemotherapy. METHODS: Ten patients with refractory sarcoma who underwent DEB-TACE therapy between January 2015 and January 2017 were identified. Clinical information and radiological data were retrospectively collected to analyze tumor response, overall survival (OS), progression-free survival and adverse events (AEs). Tumor response to DEB-TACE was assessed with modified Response Evaluation Criteria in Solid Tumors (mRECIST) guidelines applied to computed tomography or magnetic resonance imaging. RESULTS: All DEB-TACE procedures were successfully performed for ten patients with 15 tumor lesions. The median follow-up duration was 19 months and the median survival time was 21 months (range 11-30 months). The 1- and 2-year OS rate was 90 and 30%, respectively. According to the guidance of mRECIST, complete response, partial response, stable disease and progressive disease were noted in zero (0%), three (30%), four (40%) and three (30%) patients, respectively. The disease control rate and objective response rate was 70 and 30%, respectively. There were no serious AEs in patients after DEB-TACE. CONCLUSIONS: Our data showed that DEB-TACE was effective and safe for patients with soft tissue sarcoma. Therefore, DEB-TACE can be considered as an alternative treatment option for unresectable soft tissue sarcoma refractory to conventionally systemic chemotherapy. PMID- 28993946 TI - Tobacco alpha-expansin EXPA4 plays a role in Nicotiana benthamiana defence against Tobacco mosaic virus. AB - MAIN CONCLUSION: Tobacco EXPA4 plays a role in Nicotiana benthamiana defence against virus attack and affects antioxidative metabolism and phytohormone mediated immunity responses in tobacco. Expansins are cell wall-loosening proteins known for their endogenous functions in cell wall extensibility during plant growth. The effects of expansins on plant growth, developmental processes and environment stress responses have been well studied. However, the exploration of expansins in plant virus resistance is rarely reported. In the present study, virus-induced gene silencing (VIGS) and Agrobacterium-mediated transient overexpression were conducted to investigate the role of Nicotiana tabacum alpha expansin 4 (EXPA4) in modulating Tobacco mosaic virus (TMV-GFP) resistance in Nicotiana benthamiana. The results indicated that silencing of EXPA4 reduced the sensitivity of N. benthamiana to TMV-GFP, and EXPA4 overexpression accelerated virus reproduction on tobacco. In addition, our data suggested that the changes of virus accumulation in response to EXPA4 expression levels could further affect the antioxidative metabolism and phytohormone-related pathways in tobacco induced by virus inoculation. EXPA4-silenced plants with TMV-GFP have enhanced antioxidant enzymes activities, which were down-regulated in virus-inoculated 35S:EXPA4 plants. Salicylic acid accumulation and SA-mediated defence genes induced by TMV-GFP were up-regulated in EXPA4-silenced plants, but depressed in 35S:EXPA4 plants. Furthermore, a VIGS approach was used in combination with exogenous phytohormone treatments, suggesting that EXPA4 has different responses to different phytohormones. Taken together, these results suggested that EXPA4 plays a role in tobacco defence against viral pathogens. PMID- 28993947 TI - Laparoscopic left ureteral substitution using the cecal appendix after en-bloc rectosigmoidectomy: a case report and video demonstration. PMID- 28993948 TI - A model for cell migration in non-isotropic fibrin networks with an application to pancreatic tumor islets. AB - Cell migration, known as an orchestrated movement of cells, is crucially important for wound healing, tumor growth, immune response as well as other biomedical processes. This paper presents a cell-based model to describe cell migration in non-isotropic fibrin networks around pancreatic tumor islets. This migration is determined by the mechanical strain energy density as well as cytokines-driven chemotaxis. Cell displacement is modeled by solving a large system of ordinary stochastic differential equations where the stochastic parts result from random walk. The stochastic differential equations are solved by the use of the classical Euler-Maruyama method. In this paper, the influence of anisotropic stromal extracellular matrix in pancreatic tumor islets on T lymphocytes migration in different immune systems is investigated. As a result, tumor peripheral stromal extracellular matrix impedes the immune response of T lymphocytes through changing direction of their migration. PMID- 28993949 TI - Poly-N-methylated Abeta-Peptide C-Terminal fragments (MEPTIDES) reverse the deleterious effects of amyloid-beta in rats. AB - Alzheimer's disease (AD) is characterized by extracellular deposition of amyloid beta (Abeta) plaques. These protein deposits impair synaptic plasticity thereby producing a progressive decline in cognitive function. Current therapies are merely palliative and only slow cognitive decline. Poly-N-methylated Abeta Peptide C-Terminal Fragments (MEPTIDES) were recently shown to reduce Abeta toxicity in vitro and in Drosophila melanogaster, however whether these novel compounds are effective in inhibiting Abeta-induced toxicity in the mammalian brain remains unclear. We therefore investigated whether MEPTIDES have the ability to reduce the neurotoxic effects of Abeta in male Sprague-Dawley (SD) rats. Abeta42 (100 MUg, 2 mM) or vehicle (0.15 M Tris buffer) was stereotaxically injected bilaterally into the dorsal hippocampus at a rate of 1 MUl/min for 10 min. The effects on hippocampal-mediated learning were subsequently assessed using the Morris water maze (MWM). The presence of apoptotic activity was also assessed by determining the expression levels of active caspase-3 using real-time polymerase chain reaction and Western Blot techniques. In addition, half of the animals (n = 20) received an intraperitoneal (i.p.) injection of MEPTIDES (2 mg/kg) 48 h after intrahippocampal injection of Abeta42. Matrix-assisted laser desorption/ionization-time-of-flight (MALDI -TOF) mass spectrometry (MS) showed that MEPTIDES crossed the blood brain barrier (BBB) and revealed their distribution in the rat brain. Rats treated with Abeta42 displayed spatial learning deficits and increased hippocampal caspase-3 gene (CASP-3) expression which was reversed by subsequent injection of MEPTIDES. The present results show that MEPTIDES have the potential to reverse the toxic effects of Abeta42 in vivo. PMID- 28993950 TI - Competition in pharmaceuticals: more product- than price-oriented? PMID- 28993951 TI - Dinuclear adducts of di-o-iminoquinone ligands with CoII diketonates: computational insights into two-step valence tautomeric rearrangements. AB - Density functional theory (DFT) computational modeling [B3LYP*/6-311++G(d,p)] of a series of potentially valence tautomeric (VT) dinuclear 2:1 adducts of CoII bis acetylacetonate, bis-trifluoroacetylacetonate and bis-hexafluoroacetylacetonate with redox-active tetradentate di-o-iminoquinone ligands has been performed. The significant energy preference of the low-spin electromeric forms of the complexes on the basis of CoII bis-acetylacetonate points to a low probability of VT in these compounds. Electron-withdrawing CF3-groups in the diketonate moiety of the mixed-ligand complexes promote narrowing of the energy gaps between the electronic states, which allows one-step VT rearrangements to be expected in the adducts of CoII bis-trifluoromethylacetylacetonate. The most suitable energy parameters for the occurrence of two-step VT conversion (stability of the adduct with respect to dissociation into the components, small relative energies of electromeric forms and thermally achievable energy barriers to intramolecular electron transfers estimated as minimum energy crossing points) are found for the adduct of di-o-iminoquinone with CoII bis-trifluoroacetylacetonates comprising a diphenylene linker. PMID- 28993952 TI - Discordance of the Framingham cardiovascular risk score and the 2013 American College of Cardiology/American Heart Association risk score in systemic lupus erythematosus and rheumatoid arthritis. AB - Despite the increasing use of the 2013 American College of Cardiology/American Heart Association (ACC/AHA) cardiovascular (CV) risk score in clinical practice, few studies have compared this score to the Framingham risk score among rheumatologic patients. We calculated Framingham and 2013 ACC/AHA risk scores in subjects with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and assessed demographic, CV, and rheumatologic characteristics associated with discordant scores (high-risk ACC/AHA scores but low-risk Framingham scores). SLE and RA subjects drawn from two population-based cohort studies were assessed during in-person study visits. We used chi-squared tests and t tests to examine the association of discordant CV risk scores with baseline characteristics. Eleven (7.0%) of 157 SLE subjects and 11 (11.5%) of 96 RA subjects had discordant CV risk scores with high ACC/AHA scores and low Framingham scores. These findings did not significantly change when a 1.5 multiplier was applied to the Framingham score. Rheumatologic disease duration, high-sensitivity CRP levels, African American race, diabetes, current use of anti-hypertensive medication, higher age, and higher systolic blood pressure were each significantly associated with discordant risk scores. Approximately 10% of SLE and RA subjects had discordant 10-year CV risk scores. Our findings suggest that the use of the 2013 ACC/AHA risk score could result in changes to lipid-lowering therapy recommendations in a significant number of rheumatologic patients. Prospective studies are needed to compare which score better predicts CV events in rheumatologic patients, especially those with risk factors associated with discordant risk scores. PMID- 28993953 TI - Intestinal toxicity of deoxynivalenol is limited by Lactobacillus rhamnosus RC007 in pig jejunum explants. AB - Probiotics have been explored to stimulate gut health in weaned pigs, when they started to consume solid diet where mycotoxins could be present. The aim of this study was to evaluate the effect of Lactobacillus rhamnosus RC007 on the intestinal toxicity of deoxynivalenol (DON) in an ex vivo model. Jejunal explants, obtained from 5-week-old crossbred castrated male piglets, were kept as control, exposed for 3 h to 10 MUM DON, incubated for 4 h with 109 CFU/mL L. rhamnosus, or pre-incubated 1 h with 109 L. rhamnosus and exposed to DON. Histological lesions were observed, para- and transcellular intestinal permeability was measured in Ussing chambers. The expression levels of mRNA encoding six inflammatory cytokines (CCL20, IL-10, IL-1beta, TNFalpha, IL-8 and IL-22) were determined by RT-PCR. The expressions of the phosphorylated MAP kinases p42/p44 and p38 were assessed by immunoblotting. Exposure to DON induced histological changes, significantly increased the expression of CCL20, IL-1beta, TNFalpha, IL-8, IL-22 and IL-10, increased the intestinal paracellular permeability and activated MAP kinases. Incubation with L. rhamnosus alone did not have any significant effect. By contrast, the pre-incubation with L. rhamnosus reduced all the effects of DON: the histological alterations, the pro inflammatory response, the paracellular permeability and the phosphorylation of MAP kinases. Of note, L. rhamnosus did not adsorb DON and only slightly degrade the toxin. In conclusion, L. rhamnosus RC007 is a promising probiotic which, included as feed additive, can decrease the intestinal toxicity of DON. PMID- 28993954 TI - Obesity-alleviating potential of asiatic acid and its effects on ACC1, UCP2, and CPT1 mRNA expression in high fat diet-induced obese Sprague-Dawley rats. AB - The present study evaluated the effects of asiatic acid (AA), a pentacyclic triterpenoid from Centella asiatica on lipid metabolism parameters in a rat model of obesity induced using a high fat diet (HFD) for 42 days. AA (20 mg/kg body weight [BW]) was administered orally once daily for 42 days, and an orlistat treated group of rats (10 mg/kg BW) was included for comparison. Changes in BW, blood glucose levels, insulin resistance and leptin, adiponectin, amylase, and lipase levels in the blood; lipid profiles of plasma; liver antioxidants levels; and acetyl CoA carboxylase(ACC), uncoupling protein-2 (UCP2), and carnitine palmitoyltransferase-1 (CPT1) mRNA expression were observed in the experimental rats. Our results revealed that AA (20 mg/kg BW), similar to orlistat, reduced the increase in BW; increased bone mineral contents and bone mineral densities; reduced blood glucose levels, insulin resistance, leptin, plasma lipid levels; increased adiponectin, amylase, lipase levels in the blood; showed antioxidant activity; and altered mRNA expression of lipid metabolism-related genes, including ACC, UCP 2, and CPT 1, in the HFD-fed rats. From these results, we concluded that AA possesses significant anti-obesity potential through the suppression of BW gain, lipid lowering action, development of insulin and leptin sensitivity, antioxidant activity, and increased mRNA expression of lipid metabolism-related genes. PMID- 28993956 TI - Notch signaling controls sprouting angiogenesis of endometriotic lesions. AB - Angiogenesis is essential for the engraftment and growth of endometriotic lesions. In this study, we analyzed whether this process is regulated by Notch signaling. Endometriotic lesions were induced by endometrial tissue transplantation into dorsal skinfold chambers of C57BL/6 mice, which were treated with the gamma-secretase inhibitor DAPT or vehicle. Vascularization, morphology, and proliferation of the newly developing lesions were analyzed using intravital fluorescence microscopy, histology, and immunohistochemistry over 14 days. Inhibition of Notch signaling by DAPT significantly increased the number of angiogenic sprouts within the endometrial grafts during the first days after transplantation when compared to vehicle-treated controls. This was associated with an accelerated vascularization, as indicated by a higher functional microvessel density of DAPT-treated lesions on day 6. However, inhibition of Notch signaling did not affect the morphology and proliferating activity of the lesions, as previously described for tumors. Both DAPT- and vehicle-treated lesions finally consisted of cyst-like dilated glands, which were surrounded by a well-vascularized stroma and contained comparable numbers of proliferating cell nuclear antigen-positive cells. These findings demonstrate that sprouting angiogenesis in endometriotic lesions is controlled by Notch signaling. However, inhibition of Notch signaling does not have beneficial therapeutic effects on lesion development. PMID- 28993955 TI - The c.29T>C polymorphism of the transforming growth factor beta-1 (TGFB1) gene, bone mineral density and the occurrence of low-energy fractures in patients with inflammatory bowel disease. AB - Gastrointestinal tract conditions are frequently associated with low bone mineral density and increased risk of fractures due to osteoporosis, the latter concerning particularly inflammatory bowel disease (IBD) patients. One of the candidate genes involved in osteoporosis is the transforming growth factor beta-1 (TGFB1) whose polymorphisms may be responsible for the development of this disease. The aim of this study was to analyse the frequency of TGFB1 polymorphic variants and determine the association between the c.29T>C TGFB1 polymorphism, and bone mineral density and fractures in IBD patients. The study subjects included 198 IBD patients [100 suffering from Crohn's disease (CD) and 98 from ulcerative colitis (UC)] and 41 healthy volunteers as a control group. Densitometric bone measurements were obtained using dual energy X-ray absorptiometry. The TGFB1 genotyping was conducted using restriction fragments length polymorphism. We conducted an analysis of genotype distribution's concordance with Hardy-Weinberg equilibrium. We found statistically significant differences in lumbar spine (L2-L4) and femoral neck BMD and T-scores between CD, UC and control subgroups. The distribution of TGFB1 polymorphic variants among CD and UC patients was concordant with Hardy-Weinberg equilibrium. There were no statistically significant differences in densitometric parameters (lumbar spine and femoral neck BMD, T-score, and Z-score) between carriers of different TGFB1 polymorphisms among IBD (CD and UC) patients nor among controls. We have found no statistically significant differences in the prevalence of low-energy fractures between groups of different TGFB1 polymorphic variant carriers. The allele dose effect, recessive effect and dominant effect analysis did not show an association between low-energy fractures and the TGFB1 polymorphisms among CD and UC patients. We have not observed an association between the c.29T>C TGFB1 polymorphic variant and the bone mineral density within the cancellous and cortical bones (L2-L4 and femoral neck, respectively), or the occurrence of fractures among the IBD patients and their family members. PMID- 28993957 TI - Hematopoietic Stem Cell Transplantation in ADA2 Deficiency: Early Restoration of ADA2 Enzyme Activity and Disease Relapse upon Drop of Donor Chimerism. PMID- 28993958 TI - Functional Evaluation of an IKBKG Variant Suspected to Cause Immunodeficiency Without Ectodermal Dysplasia. AB - Hypomorphic IKBKG mutations in males are typically associated with anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID). Some mutations cause immunodeficiency without EDA (NEMO-ID). The immunological profile associated with these NEMO-ID variants is not fully documented. We present a 2-year-old patient with suspected immunodeficiency in which a hemizygous p.Glu57Lys IKBKG variant was identified. At the age of 1 year, he had an episode of otitis media that evolved into a bilateral mastoiditis (Pseudomonas spp). Hypogammaglobulinemia, specific (polysaccharide) antibody deficiency, and low switched memory B cell subsets were noticed. The mother was heterozygous for the variant but had no signs of incontinentia pigmenti. Patient peripheral blood mononuclear cells produced low amounts of IL-6 after stimulation with IL-1beta, Pam3CSK4, and FSL 1. In patient fibroblasts, IkappaB-alpha was degraded normally upon stimulation with IL-1beta or TNF-alpha. Transduction of wild-type and variant NEMO in NEMO-/- deficient SV40 fibroblasts revealed a slight but significant reduction of IL-6 production upon stimulation with IL-1beta and TNF-alpha. In conclusion, we demonstrated that p.Glu57Lys leads to specific immunological defects in vitro. No other pathogenic PID variants were identified through whole exome sequencing. As rare polymorphisms have been described in IKBKG and polygenic inheritance remains an option in the presented case, this study emphasizes the need for thorough functional and genetic evaluation when encountering and interpreting suspected disease-causing NEMO-ID variants. PMID- 28993959 TI - Comprehensive analysis of phospholipids in the brain, heart, kidney, and liver: brain phospholipids are least enriched with polyunsaturated fatty acids. AB - It is commonly accepted that brain phospholipids are highly enriched with long chain polyunsaturated fatty acids (PUFAs). However, the evidence for this remains unclear. We used HPLC-MS to analyze the content and composition of phospholipids in rat brain and compared it to the heart, kidney, and liver. Phospholipids typically contain one PUFA, such as 18:2, 20:4, or 22:6, and one saturated fatty acid, such as 16:0 or 18:0. However, we found that brain phospholipids containing monounsaturated fatty acids in the place of PUFAs are highly elevated compared to phospholipids in the heart, kidney, and liver. The relative content of phospholipid containing PUFAs is ~ 60% in the brain, whereas it is over 90% in other tissues. The most abundant species of phosphatidylcholine (PC) is PC(16:0/18:1) in the brain, whereas PC(18:0/20:4) and PC(16:0/20:4) are predominated in other tissues. Moreover, several major species of plasmanyl and plasmenyl phosphatidylethanolamine are found to contain monounsaturated fatty acid in the brain only. Overall, our data clearly show that brain phospholipids are the least enriched with PUFAs of the four major organs, challenging the common belief that the brain is highly enriched with PUFAs. PMID- 28993961 TI - Predictive factors for live birth after in vitro maturation of oocytes in women with polycystic ovary syndrome. AB - OBJECTIVE: In vitro maturation (IVM) of human oocytes can be an alternative treatment option to conventional in vitro fertilization. Women with polycystic ovary syndrome (PCOS) are considered the classical candidates for IVM because of the associated ovarian morphology and because IVM diminishes the risk of developing ovarian hyperstimulation syndrome. The objective of this study was to identify predictive factors for live birth in a cohort of women with PCOS who underwent IVM. METHODS: This retrospective study included 159 patients with PCOS who had IVM cycles in which single or double embryo transfer was performed. The IVM protocol included three days of gonadotropin ovarian stimulation and hCG priming when the leading follicle size was 10-12 mm. Collected cumulus-oocyte complexes were cultured for 24 h for maturation. Intracytoplasmic sperm injection (ICSI) was used for fertilization. Embryo transfer was performed two days after fertilization. Demographic and clinical parameters were analyzed with logistic regression to identify predictors for live birth. RESULTS: The women's mean age was 27.4 years, the mean number of retrieved oocytes was 14, and the live birth rate was 34.6%. The logistic regression revealed the following significant factors for live birth: infertility duration (OR 0.9; 95% CI, 0.82-0.98), number of collected oocytes (OR 1.56; 95% CI, 1.01-3.2), embryo cell number (OR 2.1; 95% CI, 1.4-3.5), and embryo grade (OR 1.84; 95% CI, 1.13-4.2). CONCLUSION: Infertility duration, oocyte number, embryo cell number, and embryo grade were the most significant predictors for live birth after IVM in PCOS patients. These prognostic factors can be used when planning treatment or counselling patients. PMID- 28993960 TI - Effect of environmental parameters on biodiversity of the fungal component in lithic Antarctic communities. AB - A wide sampling of rocks, colonized by microbial epi-endolithic communities, was performed along an altitudinal gradient from sea level to 3600 m asl and sea distance from the coast to 100 km inland along the Victoria Land Coast, Antarctica. Seventy-two rock samples of different typology, representative of the entire survey, were selected and studied using denaturing gradient gel electrophoresis to compare variation in fungal diversity according to environmental conditions along this altitudinal and sea distance transect. Lichenized fungi were largely predominant in all the samples studied and the biodiversity was heavily influenced even by minimal local variations. The n-MDS analysis showed that altitude and sea distance affect fungal biodiversity, while sandstone allows the communities to maintain high biodiversity indices. The Pareto-Lorenz curves indicate that all the communities analyzed are highly adapted to extreme conditions but scarcely resilient, so any external perturbation may have irreversible effects on these fragile ecosystems. PMID- 28993962 TI - Deep Sequencing Reveals the Significant Involvement of cAMP-Related Signaling Pathways Following Sciatic Nerve Crush. AB - Peripheral nerve injury and regeneration is a complex biological process jointly mediated by numerous factors. Cyclic adenosine monophosphate (cAMP) modifies the cellular behaviors of neurons and Schwann cells, and thus may contribute to peripheral nerve regeneration. Despite the importance of cAMP, the temporal and spatial expressions of genes involved in cAMP-related signaling pathways during peripheral nerve regeneration remain unclear. In the current study, by using rat sciatic nerve crush model, we analyzed previously obtained RNA deep sequencing data, explored the significance of cAMP-mediated signaling pathway and protein kinase A (PKA) signaling pathway after peripheral nerve injury, and examined the expression patterns of genes involved in these cAMP-related signaling pathways. Our results, from the genetic aspect, emphasized the critical involvement of cAMP related signaling pathways, identified the dynamic changes of some key signaling cascades, and may help the discovery of potential therapeutic targets for peripheral nerve repair and regeneration. PMID- 28993963 TI - A double-blind placebo-controlled randomised trial of omega-3 supplementation in children with moderate ADHD symptoms. AB - OBJECTIVE: Clinical trials and inconclusive meta-analyses have investigated the effects of omega-3 supplements in children with Attention-Deficit Hyperactivity Disorder (ADHD). We performed a randomised placebo-controlled trial to evaluate the efficacy of omega-3 fatty acids. METHODS: Children aged 6-15 years with established diagnosis of ADHD were randomised 1:1 to receive either supplements containing docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) or a placebo for 3 months. Psychotropic or omega-3-containing treatments were not authorised during the study. The primary outcome was the change in the Attention Deficit Hyperactivity Disorder Rating Scale version 4 (ADHD-RS-IV). Other outcomes included safety, lexical level (Alouette test), attention (Test of Attentional Performance for Children-KiTAP), anxiety (48-item Conners Parent Rating Scale-Revised-CPRS-R), and depression (Children's Depression Inventory CDI). RESULTS: Between 2009 and 2011, 162 children were included in five French child psychiatry centres. The mean age was 9.90 (SD 2.62) years and 78.4% were boys. The inclusion ADHD-RS-IV at was 37.31 (SD 8.40). The total ADHD-RS-IV score reduction was greater in the placebo group than in the DHA-EPA group: -19 (-26, 12) % and -9.7 (-16.6, -2.9) %, respectively, p = 0.039. The other components of the Conners score had a similar variation but the differences between groups were not significant. Two patients in the DHA-EPA group and none in the placebo group experienced a severe adverse event (hospitalisation for worsening ADHD symptoms). CONCLUSION: This study did not show any beneficial effect of omega-3 supplement in children with mild ADHD symptoms. PMID- 28993964 TI - Estimating cadmium concentration in the edible part of Capsicum annuum using hyperspectral models. AB - Hyperspectral remote sensing can be applied to the rapid and nondestructive monitoring of heavy-metal pollution in crops. To realize the rapid and real-time detection of cadmium in the edible part (fruit) of Capsicum annuum, the leaf spectral reflectance of plants exposed to different levels of cadmium stress was measured using hyperspectral remote sensing during four growth stages. The spectral indices or bands sensitive to cadmium stress were determined by correlation analysis, and hyperspectral estimation models for predicting the cadmium content in the fruit of C. annuum during the mature growth stage were established. The models were cross validated by taking the sensitive spectral indices in the bud stage and the sensitive spectral bands in the flowering stage as the input variables. The results indicated that cadmium accumulated in the leaves and fruit of C. annuum and leaf cadmium content in the three early growth stages were correlated with the cadmium content of the pepper in the mature stage. Leaf spectral reflectance was sensitive to cadmium stress, and the first derivative of the original spectral reflectance was strongly correlated with leaf cadmium content during all growth stages. Among the established models, the multiple regression model based on the sensitive spectral bands in the flowering stage was optimal for predicting fruit cadmium content of the pepper. This model provides a promising method to ensure food safety during the early growth stage of the plant. PMID- 28993965 TI - An optimization model to determine appointment scheduling window for an outpatient clinic with patient no-shows. AB - This paper investigates appointment scheduling for an outpatient department in West China Hospital (WCH), one of the largest single point of access hospitals in the world. Our pilot data analysis shows that the appointment system at WCH can be improved through leveraging the scheduling window (i.e., the number of days in advance a patient makes an appointment for future services). To gain full insight into this strategy, our study considers two cases, based on if patients are willing to wait for scheduled appointments or not. We developed a stylized single server queueing model to find optimal scheduling windows. Results show that, when patients are less sensitive to time delay (i.e., patients will wait for scheduled services), levering scheduling windows is not effective to minimize the total cost per day of the appointment system. In contrast, when patients are sensitive to time delay (i.e., patients may find services elsewhere), then our model considers the potential cost of physician idle time. The modeling results indicate that the total cost per day is relatively sensitive to the magnitude of scheduling window. Thus, adopting a proper scheduling window is very important. In addition, our study proves that the cost functions of both cases are quasi concave, which are also validated by actual data drawn from the Healthcare Information System at WCH. A comparison of numerical results between two cases is made to draw further managerial insights into scheduling policies for WCH. Discussion of our findings and research limitations are also provided. PMID- 28993966 TI - Neuroscience in Nigeria: the past, the present and the future. AB - The science of the brain and nervous system cuts across almost all aspects of human life and is one of the fastest growing scientific fields worldwide. This necessitates the demand for pragmatic investment by all nations to ensure improved education and quality of research in Neurosciences. Although obvious efforts are being made in advancing the field in developed societies, there is limited data addressing the state of neuroscience in sub-Saharan Africa. Here, we review the state of neuroscience development in Nigeria, Africa's most populous country and its largest economy, critically evaluating the history, the current situation and future projections. This review specifically addresses trends in clinical and basic neuroscience research and education. We conclude by highlighting potentially helpful strategies that will catalyse development in neuroscience education and research in Nigeria, among which are an increase in research funding, provision of tools and equipment for training and research, and upgrading of the infrastructure at hand. PMID- 28993967 TI - Outcomes after inferior vena cava filter placement in cancer patients diagnosed with pulmonary embolism: risk for recurrent venous thromboembolism. AB - Venous thromboembolism (VTE) is a common complication in cancer patients and anticoagulation (AC) remains the standard of care for treatment. Inferior vena cava (IVC) filters may also used to reduce the risk of pulmonary embolism, either alone or in addition to AC. Although widely used, data are limited on the safety and efficacy of IVC filters in cancer patients. We performed a retrospective review of outcomes after IVC filter insertion in a database of 1270 consecutive patients with cancer-associated pulmonary embolism (PE) at our institution between 2008 and 2009. Outcomes measured included rate of all recurrent VTE, recurrent PE, and overall survival within 12 months. 317 (25%) of the 1270 patients with PE had IVC filters placed within 30 days of the index PE event or prior to the index PE in the setting of prior DVT. Patients with IVC filters had markedly lower overall survival (7.3 months) than the non-IVC filter patients (13.2 months). Filter patients also had a lower rate of AC use at time of initial PE. There was a trend towards higher recurrent VTE in patients with IVC filters (11.9%) compared to non-filter patients (7.7%), but this was not significant (p = 0.086). The risk of recurrent PE was similar between the IVC filter cohort (3.5%) and non-filter group (3.5%, p = 0.99). Cancer patients receiving IVC filters had a similar risk of recurrent PE, but a trend towards more overall recurrent VTE. The filter patients had poorer overall survival, which may reflect a poorer cancer prognosis, and had greater contraindication to AC; therefore these patients likely had a higher inherent risk for recurrent VTE. A prospective study would be helpful for further clarification on the partial reduction in the recurrent PE risk by IVC filter placement in cancer patients. PMID- 28993968 TI - Enteral Autonomy with Teduglutide Treatment of Intestinal Failure/Short Bowel Syndrome with Depleted Central Venous Access. PMID- 28993969 TI - Grape Seed Proanthocyanidin and Swimming Exercise Protects Against Cognitive Decline: A Study on M1 Acetylcholine Receptors in Aging Male Rat Brain. AB - Decline in cognition is one of the earliest signs of normal brain aging. Several dietary and non-pharmacological approaches have been tested to slow down this process. The aim of the present study was to assess the influence of grape seed proanthocyanidin extract (GSPE) either individually or in combination with swimming training on acetylcholine esterase activity (AChE) and m1 acetylcholine receptor (m1AChR) on the extent of cognitive decline with aging. The experimental protocol included the oral administration of GSPE (400 mg/kg body weight) for 14 weeks to 4 (adult) and 18-month-old (middle-aged) male Wistar rats along with swimming training. They were subjected to behavioral testing followed by biochemical and immunohistochemical analysis. The results demonstrated that GSPE supplementation and swimming training either individually or in combination had an improvement on acquisition and working memory with reduced AChE activity in the medial prefrontal cortex (mPFC) and hippocampus (HC). Immunohistochemical and qRT-PCR evaluation showed an increase in m1AChR protein and mRNA in the CA1 region of HC and also mPFC upon swimming training with GSPE treatment. These beneficial and synergistic effects of GSPE and swimming training are suggestive as interventions in modulating the cognitive function, with GSPE alone being more suitable for middle-aged individuals. PMID- 28993971 TI - Ancestral Sequence Reconstruction with Maximum Parsimony. AB - One of the main aims in phylogenetics is the estimation of ancestral sequences based on present-day data like, for instance, DNA alignments. One way to estimate the data of the last common ancestor of a given set of species is to first reconstruct a phylogenetic tree with some tree inference method and then to use some method of ancestral state inference based on that tree. One of the best known methods both for tree inference and for ancestral sequence inference is Maximum Parsimony (MP). In this manuscript, we focus on this method and on ancestral state inference for fully bifurcating trees. In particular, we investigate a conjecture published by Charleston and Steel in 1995 concerning the number of species which need to have a particular state, say a, at a particular site in order for MP to unambiguously return a as an estimate for the state of the last common ancestor. We prove the conjecture for all even numbers of character states, which is the most relevant case in biology. We also show that the conjecture does not hold in general for odd numbers of character states, but also present some positive results for this case. PMID- 28993970 TI - Factors affecting palatability of four submerged macrophytes for grass carp Ctenopharyngodon idella. AB - Grass carp can weaken the growth and reproductive capacity of submerged macrophytes by consuming valuable tissues, but factors affecting palatability of submerged macrophytes for grass carp rarely are considered. In this study, relative consumption rate of grass carp with regard to submerged macrophytes was in the following order: Hydrilla verticillata > Vallisneria natans > Ceratophyllum demersum > Myriophyllum spicatum. Firmness of macrophytes was in the following order: M. spicatum > C. demersum > H. verticillata = V. natans, whereas shear force was M. spicatum > C. demersum > H. verticillata > V. natans. After crude extracts of M. spicatum were combined with H. verticillata, grass carp fed on fewer macrophyte pellets that contained more plant secondary metabolites (PSMs). This indicated that structure and PSMs affected palatability of macrophytes.PSMs do not contribute to reduction in palatability through inhibition of intestinal proteinases activity, but they can cause a decrease in the abundance of Exiguobacterium, Acinetobacter-yielding proteases, lipases, and cellulose activity, which in turn can weaken the metabolic capacity of grass carp and adversely affect their growth. Thus, the disadvantages to the growth and development of grass carp caused by PSMs may drive grass carp to feed on palatable submerged macrophytes with lower PSMs. PMID- 28993972 TI - The Effect of Acute and Repeated Stress on CRH-R1 and CRH-R2 mRNA Expression in Pituitaries of Wild Type and CRH Knock-Out Mice. AB - The activation of the HPA axis is the endocrine measure of stress responsiveness that is initiated by corticotropin-releasing hormone (CRH). CRH exerts its effects via CRHR1 and CRH-R2 receptors coupled to the cAMP signaling system and this process involves transcription factor cAMP-responsive element-binding protein (CREB).This study investigated the role of CRH and the possible involvement of CREB in gene regulation of CRH receptor, under basal conditions and after stress application in the pituitary. We used wild type (wt +/+) controls and CRH knock-out (CRH-KO -/-) male mice. Using CRH-deficient mice, we were able to investigate the consequences of the lack of the CRH on the expression of CRH receptors and transcriptional regulation mediated by CREB. We estimated the effect of acute (IMO 1*) and repeated (IMO 7*) restraint stressors lasting 30 and 120 min on the expression of mRNA CREB, CRH-R1, and CRH-R2 by qPCR. We found very significant difference in the expression of these peptides under the effect of single and repeated stress in control and CRH-KO mice. Our results indicate that both CRH receptors and CREB might be involved in the regulation of stress response in the pituitary of mice. We propose that regulation of the stress response may be better understood if more were known about the mechanisms of CRH receptor signal transduction and involvement of CREB system. PMID- 28993973 TI - CRISPR/Cas9-mediated knockout of myostatin in Chinese indigenous Erhualian pigs. AB - CRISPR/Cas9 has emerged as one of the most popular genome editing tools due to its simple design and high efficiency in multiple species. Myostatin (MSTN) negatively regulates skeletal muscle growth and mutations in myostatin cause double-muscled phenotype in various animals. Here, we generated myostatin mutation in Erhualian pigs using a combination of CRISPR/Cas9 and somatic cell nuclear transfer. The protein level of myostatin precursor decreased dramatically in mutant cloned piglets. Unlike myostatin knockout Landrace, which often encountered health issues and died shortly after birth, Erhualian pigs harboring homozygous mutations were viable. Moreover, myostatin knockout Erhualian pigs exhibited partial double-muscled phenotype such as prominent muscular protrusion, wider back and hip compared with wild-type piglets. Genome editing in Chinese indigenous pig breeds thus holds great promise not only for improving growth performance, but also for protecting endangered genetic resources. PMID- 28993974 TI - Unique variations and characteristics of iridocorneal endothelial syndrome in China: a case series of 58 patients. AB - PURPOSE: Iridocorneal endothelial (ICE) syndrome is a rare condition, and unique characteristics in Chinese patients can make diagnosis difficult. Our purpose was to describe the clinical characteristics and variations of ICE syndrome in 58 consecutive Chinese patients. METHODS: The clinical data of consecutive patients with ICE syndrome who were seen between 2008 and 2011 at the glaucoma clinic of our ophthalmology department were retrospectively reviewed. The diagnostic criteria for ICE syndrome were a "hammered-silver" appearance of the corneal endothelium and specular microscopy showing ICE cells characterized by the absence of a hexagonal appearance, dark areas within the cells, and a light-dark reversal pattern. The general characteristics of the cornea, iris, pupil, and anterior chamber angles were compiled and examined. RESULTS: Fifty-eight patients with ICE syndrome were identified: 26 had Chandler's syndrome (CS), 23 Cogan Reese syndrome, and nine progressive iris atrophy (PIA). The incidence of glaucoma was 98%. Twenty-three (39.7%) patients had atypical ICE syndrome. Intraocular pressure was relatively high in 13 patients with slightly damaged irises, while the corneal endothelium remained relatively intact. Slit lamp examination showed an intact iris in ten patients (17.2%), with massive deposition of black pigment in the anterior chamber angle. In the 25 patients in whom the anterior chamber angle was only partially closed, 80% of the anterior chamber angles were hyperpigmented. CONCLUSIONS: CS is the most common variation of ICE syndrome in Chinese patients, and PIA is the least common. A slight change or an intact iris under slit lamp examination is a characteristic of ICE syndrome. PMID- 28993975 TI - Mood disorders are highly prevalent in patients investigated with a multiple sleep latency test. AB - PURPOSE: Excessive daytime sleepiness (EDS) is a debilitating symptom which occurs commonly in both primary sleep and mood disorders. The prevalence of mood disorders in patients with EDS, evaluated objectively with a mean sleep latency test (MSLT), has not been reported. We hypothesize that mood disorders are highly prevalent in patients being investigated for EDS. This study aims to report the prevalence of mood disorder in the MSLT population and investigate the association between mood disorder and objective and subjective scores of sleepiness. METHODS: A retrospective multicenter study of adults with a MSLT and Hospital Anxiety and Depression Score (HADS) identified over a 3-year period. The HADS is a validated questionnaire in detecting depression (HADS-D >= 8) and anxiety (HADS-A >= 11) in the sleep clinic population. Data collected included demographics, medical, and sleep study information. Mood disorder prevalence was compared to the general sleep clinic population. Correlation between measures of sleepiness and mood was performed. RESULTS: Two hundred twenty patients were included with mean age 41.1 +/- 15.7 years, mean body mass index 28.6 kg/m2 of whom 30% had anxiety (HADS-A > 11) and 43% depression (HADS-D > 8). Mean results for the cohort are ESS 13.7, mean sleep latency 11.5 min, HADS-A 8.2, and HADS-D 7. There was no significant correlation between objective sleepiness, as measured by the mean sleep latency, and either HADS-A (-0.006, p = 0.93) or HADS-D score (0.002, p = 0.98). There was, however, a weak correlation between subjective sleepiness, as measured by the ESS, and the mean sleep latency (-0.25, p < 0.01), HADS-A (0.15, p = 0.03), and HADS-D (0.2, p = 0.004). There was no significant association between diagnosis of hypersomnia disorders and presence of anxiety (p = 0.71) or depression (p = 0.83). CONCLUSIONS: Mood disorders are highly prevalent in the MSLT population. There was a weak correlation found between subjective measures of sleepiness and mood disorders, but not between objective measures of sleepiness and mood disorders. Routine screening for mood disorders in patients with hypersomnolence should be considered. PMID- 28993977 TI - Questions about horse spleen ferritin crossing the blood brain barrier via mouse transferrin receptor 1. PMID- 28993976 TI - Boric Acid and Commercial Organoboron Products as Inhibitors of Drug-Resistant Candida albicans. AB - Clinical use of boric acid as a topical antifungal in women who have failed standard antifungal therapy with azole drugs has been used sporadically for decades. Our previous in vitro work showing inhibition of Candida albicans growth was conducted on clinical isolates without antifungal drug susceptibility profiling. Here, we report that boric acid restricts growth of drug-resistant Candida albicans and inhibits hyphal growth and diminishes cell volume. The availability of over-the-counter organoboron compounds intended for use as oral nutritional supplements led us to determine if these also were inhibitory toward resistant Candida and show here that they also possess antifungal activity. Candida glabrata was also found to be inhibited by boric acid and organoboron compounds. Further development of organoboron compounds as topical therapeutics is of potential value. PMID- 28993978 TI - Anemia in patients with ulcerative colitis in remission: A study from western India. AB - BACKGROUND: Anemia is common in patients with active ulcerative colitis. We aimed to study the anemia profile in patients with ulcerative colitis in clinical remission. METHODS: Sixty-four patients with ulcerative colitis and with a clinical Mayo score less than 3 for at least 3 months were evaluated for anemia. Initial screening was done by hemogram and only patients with anemia were evaluated further for the cause of anemia. We also screened a control population for anemia. Patients with mild anemia were given oral iron, moderate anemia were given intravenous iron and severe anemia were given blood transfusion. RESULTS: The mean hemoglobin in ulcerative colitis patients was 11.75 g/dL and in controls was 13.1 g/dL (p=0.011). The prevalence of anemia was 53.1% in the ulcerative colitis patients and 13.3% in the controls (p=<0.001). 58.8% had mild anemia, 29.4% had moderate anemia and 8.8% had severe anemia. Iron deficiency was the most common cause of anemia (70.5%) followed by anemia of chronic disease combined with iron deficiency in 23.5%. Ferritin levels did not correlate with hemoglobin levels. Oral iron increased the hemoglobin by 1.4 g/dL and intravenous iron by 2.2 g/dL at 1 month. CONCLUSION: Anemia was seen in more than half of patients with ulcerative colitis in clinical remission, iron deficiency being the most common cause. PMID- 28993980 TI - Characterization, Cytotoxicity, and Genotoxicity of TiO2 and Folate-Coupled Chitosan Nanoparticles Loading Polyprenol-Based Nanoemulsion. AB - The structure and bioactivity of Ginkgo biloba leaves polyprenol (GBP) are similar to that of dolichol which widely exists in human and mammalian organs. GBP possesses potential pharmacological activities against cancer. This study involved oil-in-water type nanoemulsion (NE) loading GBP was prepared by dissolving polyprenol in nanoemulsion of sodium tripolyphosphate (TPP)/TiO2 solution, Triton X-100, and 1-octanol by inversed-phase emulsification (EIP) and ultrasonic emulsification (UE) method. Folic acid (FA)-coupled chitosan (CS) nanoparticles (NPs), GBP-FA-CS-NPs and GBP-TiO2-FA-CS-NPs, were fabricated by ionic cross-linking of positively charged FA-CS conjugates and negatively charged nanoemulsion with TPP/TiO2. And characterizations of them were investigated by TEM, SEM, FTIR, particle size, and zeta potential. The cytotoxic and genotoxic effects of GBP-TiO2-FA-CS-NP treatment were higher than GBP-NE, GBP-FA-CS-NPs, TiO2-NE, GBP-TiO2-NE, TiO2-FA-CS-NPs, and GBP-TiO2-FA-CS-NP treatment at the same tested concentrations in HepG2 cells. GBP-TiO2-FA-CS-NPs at low TiO2 concentration (from 1 to 2.5 MUg/ml) showed good inhibition capacity on HepG2 cells and low cytotoxic and genotoxic effects on HL-7702 cells. The possible mechanism of cytotoxicity on GBP-TiO2-FA-CS-NPs against HepG2 cells is by preventing excessive intracellular Ca2+ into extracellular spaces via inhibiting Ca2+-ATPase and Ca2+/Mg2+-ATPase. PMID- 28993979 TI - Methamphetamine Augments Concurrent Astrocyte Mitochondrial Stress, Oxidative Burden, and Antioxidant Capacity: Tipping the Balance in HIV-Associated Neurodegeneration. AB - Methamphetamine (METH) use, with and without human immunodeficiency virus (HIV)-1 comorbidity, exacerbates neurocognitive decline. Oxidative stress is a probable neurotoxic mechanism during HIV-1 central nervous system infection and METH abuse, as viral proteins, antiretroviral therapy and METH have each been shown to induce mitochondrial dysfunction. However, the mechanisms regulating mitochondrial homeostasis and overall oxidative burden in astrocytes are not well understood in the context of HIV-1 infection and METH abuse. Here, we report METH mediated dysregulation of astrocyte mitochondrial morphology and function during prolonged exposure to low levels of METH. Mitochondria became larger and more rod shaped with METH when assessed by machine learning, segmentation analyses. These changes may be mediated by elevated mitofusin expression coupled with inhibitory phosphorylation of dynamin-related protein-1, which regulate mitochondrial fusion and fission, respectively. While METH decreased oxygen consumption and ATP levels during acute exposure, chronic treatment of 1 to 2 weeks significantly enhanced both when tested in the absence of METH. Together, these changes significantly increased not only expression of antioxidant proteins, augmenting the astrocyte's oxidative capacity, but also oxidative damage. We propose that targeting astrocytes to reduce their overall oxidative burden and expand their antioxidant capacity could ultimately tip the balance from neurotoxicity towards neuroprotection. PMID- 28993981 TI - Surgical treatment of marginal osteochondral impaction in acetabular fractures. AB - PURPOSE: Clinical and radiological evaluation of the results of the technique of elevation and grafting of osteochondral marginal impaction fragment of posterior wall acetabular fractures. METHODS: Twenty patients available for this study had fracture acetabulum with marginal impaction fragment. Elevation, reduction and bone graft impaction of the defect were the technique in all cases. Follow-up was at least for 1 year. Evaluation of patient was done clinically by modified Merle d'Aubigne and Postel score and radiologically by Matta's criteria of reduction quality and that of radiological hip evaluation. Ficat criteria for avascular necrosis and Brocker criteria were used for evaluation of heterotopic ossification. RESULTS: Radiologically, according to the Matta's criteria of reduction quality there were anatomic reduction in 16 patients (80%) and satisfactory reduction in 4 patients (20%). Clinical assessments based on modified Merle d'Aubigne and Postel score include 4 (20%) excellent scores, 12 (80%) good scores, 3 (15%) fair results and poor in one patient who had revision by total hip replacement. CONCLUSION: Diagnose of marginal impaction fragment preoperatively makes operative technique by elevation, reduction, bone graft packing and fixation mandatory to obtain anatomic reduction and favorable outcome. This technique should be completed before final fixation of the main fracture acetabulum. PMID- 28993982 TI - Comparative Assessment on the Expression Level of Recombinant Human Follicle Stimulating Hormone (FSH) in Serum-Containing Versus Protein-Free Culture Media. AB - Production of recombinant pharmaceutical proteins has made a great contribution to modern biotechnology. At present, quick advances in protein expression lead to the enhancement of product quantity and quality as well as reduction in timescale processing. In the current study, we assessed the expression level of recombinant human follicle-stimulating hormone (rhFSH) in adherent and suspension Chinese hamster ovary (CHO) cell lines by cultivation in serum-containing and chemically defined, protein-free media. The expression cassette entailing FSH subunits was transfected to CHO/dhfr- and CHO DG44 cell lines, and gene amplification was achieved using dihydrofolate reductase (DHFR)/methotrexate (MTX) system. Afterward, the expression level of rhFSH was studied using real-time PCR, Western blotting and ELISA. Our achievements revealed that stepwise increase in MTX [up to 2000 nano-molar (nM)] leads to boost the expression level of rhFSH mRNA in both cell lines, although DG44 have better results, as mRNA expression level reached 124.8- and 168.3-fold in alpha and beta subunits, respectively. DG44 cells have also the best protein production in 2000 nM MTX, which reached 1.7 fold in comparison with that of the mock group. According to the above results and many advantages of protein-free media, DG44 is preferable cell line for future steps. PMID- 28993984 TI - Facial soft tissue volume decreases during metreleptin treatment in patients with partial and generalized lipodystrophy. AB - PURPOSE: Lipodystrophy (LD) patients suffer from loss or maldistribution of subcutaneous adipose tissue accompanied by dysregulation of several adipocyte secreted factors, e.g., leptin. The effect of recombinant leptin (metreleptin) therapy on facial soft tissue volume in patients with non-human immunodeficiency virus LD has not been quantified to date. METHODS: Eight LD patients (six female, two male; six familial partial LD [FPLD], two generalized LD) were treated with metreleptin over 1 year. Anthropometric parameters and 3D stereophotogrammetric imaging of the patients' faces were assessed at baseline and after 1 year of metreleptin treatment. RESULTS: Median fat mass was significantly reduced during metreleptin treatment from 22.3 kg at baseline to 20.0 kg at 1 year (p = 0.031); however, body weight, body mass index, and waist-to-hip ratio were not significantly affected. Five of the six patients with FPLD lost between 4 and 114 cm3 of facial soft tissue volume in the pre-auricular, buccal, and submandibular area during metreleptin treatment whereas a slight volume gain was seen in one FPLD patient. The two patients with generalized LD developed a volume loss of 20 and 8 cm3 in the buccal region between baseline and 1 year of metreleptin therapy, respectively. CONCLUSIONS: Metreleptin replacement leads to loss of facial soft tissue volume in FPLD and generalized LD. However, volume changes in most patients are not visible by the naked eye. PMID- 28993986 TI - ESMRMB 2017, 34th Annual Scientific Meeting, Barcelona, ES, October 19-October 21: Electronic Posters / Paper Posters / Clinical Review Posters / Software Exhibits. PMID- 28993987 TI - ESMRMB 2017, 34th Annual Scientific Meeting, Barcelona, ES, October 19-October 21: Abstracts, Thursday. PMID- 28993985 TI - Gastroesophageal Reflux After Sleeve Gastrectomy: a Prospective Mechanistic Study. AB - BACKGROUND: Evolution of gastroesophageal reflux disease (GERD) after sleeve gastrectomy (SG) is controversial. Some authors report worsening or improvement of preoperative GERD, others the occurrence of de novo GERD between 5 and 69%. AIMS: The aims of this study are to evaluate the evolution of GERD after SG by ambulatory 24-h pH monitoring (APM) and to determine pre- and postoperative clinical and manometric factors associated with its evolution. METHODS: Between 2013 and 2015, 47 patients operated in our center performed APM before and 1 year (14.8 +/- 4.9 months) after SG. GERD was defined as a percentage of time with esophageal pH < 4 (TpH < 4) > 4.2. Among them, 30 had pre- and postoperative high resolution esophageal manometry (HRM). RESULTS: Thirty-one patients (66%) had no preoperative GERD (group 1), and 16 had preoperative GERD (group 2). One year after SG, mean TpH < 4 increased significantly in group 1 (5.8 +/- 4.6 vs. 1.8 +/ 1.1%, p < 0.01) whereas it was not modified in group 2 (7.4 +/- 6.6 vs. 6.6 +/- 2.6%). In group 1, 16 patients (52%) had de novo GERD whereas in group 2, 7 had no more GERD, 3 improved, and 6 worsened. Maximal intragastric pressure after swallows increased significantly at postoperative HRM only in patients with de novo GERD (49.2 +/- 22.0 vs. 25.4 +/- 9.4 mmHg, p = 0.03). No preoperative clinical or manometric parameters were predictive of postoperative GERD. CONCLUSIONS: One year after SG, esophageal acid exposure globally worsened, mostly because of de novo GERD, whereas 63% patients with preoperative GERD improved, without preoperative predictive clinical or manometric factor. PMID- 28993988 TI - ESMRMB 2017, 34th Annual Scientific Meeting, Barcelona, ES, October 19-October 21: Abstracts, Saturday. PMID- 28993983 TI - Skin Manifestations Associated with Autoimmune Liver Diseases: a Systematic Review. AB - Autoimmune liver diseases, which include mainly autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis, and the variant syndromes, are often associated with extrahepatic autoimmune diseases. However, the association with cutaneous diseases is less well described. In the present article, we provide a systematic literature review on skin manifestations linked to each of these four autoimmune liver diseases, excluding skin manifestations of systemic diseases. The association of autoimmune hepatitis with vitiligo is well known, with a particular striking association with type 2 autoimmune hepatitis, a condition occurring almost entirely in children and adolescents, much rarer and more aggressive than type 1 autoimmune hepatitis; probable associations are also identified with alopecia areata, psoriasis, and pyoderma gangrenosum. Primary biliary cholangitis is not linked to lichen planus as previously assumed, but to vitiligo, psoriasis and the very rare amicrobial pustulosis of the folds. The proposed diagnostic criteria for this latter condition include the presence of anti-mitochondrial autoantibodies, the serological hallmark of primary biliary cholangitis. The very strong association of primary sclerosing cholangitis with inflammatory bowel diseases hampers the search for an association with skin diseases, since inflammatory bowel diseases have a strong association with various dermatological condition, including neutrophilic dermatoses and erythema nodosum. Nevertheless, a probable association of primary sclerosing cholangitis with psoriasis is identified in this review. Variant syndromes, also called overlap syndromes, are likely associated with vitiligo as well, which is not surprising, since autoimmune hepatitis is a feature of these conditions and they may share regions of the MHC. PMID- 28993989 TI - ESMRMB 2017, 34th Annual Scientific Meeting, Barcelona, ES, October 19-October 21: Abstracts, Friday. PMID- 28993991 TI - POCUS in perioperative medicine: a North American perspective. AB - Ultrasound (US) performed at the point of care has found fertile ground in perioperative medicine. In the hands of anesthesiologists, transesophageal echocardiography (TEE) has become established as a powerful diagnostic and monitoring tool in the perioperative care of cardiac and non-cardiac patients. A number of point-of-care US (POCUS) applications are relevant to perioperative care, including airway, cardiac, lung and gastric US. Although guidelines exist to define the scope of practice for basic and advanced TEE, there remains a lack of such guidelines for perioperative point-of-care ultrasound (POCUS), despite a number of recent calls for action in the academic anesthesia community. POCUS training has been integrated into anesthesia residency curricula in Canada and the United States of America (USA). However, a nation-wide curriculum is still lacking. Many limitations to the development of perioperative POCUS curricula exist, including the need to define the scope of practice and design integrated longitudinal learning approaches. The main anesthesiologist societies in both the USA and Canada are promoting the development of guidelines and have introduced POCUS courses into their national conferences. Although bedside US imaging has been integrated into the curricula of many medical schools in North America, the need for specific national guidelines for the training and practice of POCUS in the perioperative setting by anesthesiologists is crucial to the further development of POCUS in perioperative medicine. PMID- 28993992 TI - Sulfur-Containing Agrochemicals. AB - Modern agricultural chemistry has to support farmers by providing innovative agrochemicals. In this context, the introduction of sulfur atoms into an active ingredient is still an important tool in modulating the properties of new crop protection compounds. More than 30% of today's agrochemicals contain at least one sulfur atom, mainly in fungicides, herbicides and insecticides. A number of recently developed sulfur-containing agrochemical candidates represent a novel class of chemical compounds with new modes of action, so we intend to highlight the emerging interest in commercially active sulfur-containing compounds. This chapter gives a comprehensive overview of selected leading sulfur-containing pesticidal chemical families namely: sulfonylureas, sulfonamides, sulfur containing heterocyclics, thioureas, sulfides, sulfones, sulfoxides and sulfoximines. Also, the most suitable large-scale synthetic methods of the recently launched or provisionally approved sulfur-containing agrochemicals from respective chemical families have been highlighted. PMID- 28993993 TI - A Practical Guide About Tattooing in Patients with Chronic Skin Disorders and Other Medical Conditions. AB - With tattoos becoming increasingly mainstream, dermatologists are more and more often consulted by patients who are considering getting an ornamental, cosmetic, or even a medical tattoo, and who subsequently ask for advice. This includes not only patients with chronic skin diseases such as psoriasis or atopic dermatitis but also patients with other medical conditions. This review first explores the reasons why patients may want to get a tattoo and aims to offer some key information to dermatologists on what they should know about tattooing and the main risks associated with this procedure. Second, the risks and recommendations of tattooing in patients with specific skin diseases are described more in detail, and the relative and strict contraindications discussed, including the necessity to discontinue certain treatments that could influence the outcome of the procedure and the final result. Our aim was to provide dermatologists with the current knowledge they need to help their patients make adequate and informed choices on skin art, focusing specifically on considerations in patients with chronic skin conditions. Finally, other aspects regarding some general systemic conditions and concomitant diseases that the patient could present are also addressed. In particular, the risks of tattooing in patients with diabetes, coagulation disorders, heart conditions, immunosuppressive treatments, and pregnancy are discussed. PMID- 28993994 TI - Efficacy and factors determining the outcome of dorsal root entry zone lesioning procedure (DREZotomy) in the treatment of intractable pain syndrome. AB - BACKGROUND: Chronic pain is a disabling condition that adversely affects patient quality of life. The dorsal root entry zone lesioning procedure (DREZotomy) is a modality used to treat intractable pain caused by insults to neural structures. This study aimed to investigate the efficacy of and the factors that determine the outcome of microsurgical DREZotomy (MDT). METHOD: All consecutive patients who underwent MDT for treatment of intractable pain during September 2008 to December 2016 were enrolled. Demographic data, clinical characteristics, intraoperative findings, and postoperative outcomes were analyzed. RESULTS: The 40 included patients underwent MDT for relief of intractable pain caused by 27 brachial plexus injuries (BPIs), 6 spinal cord injuries, 3 neoplasms, and 4 other causes. A significant reduction in pain was observed post-MDT for both average (p < 0.001) and maximal pain (p < 0.001). Favorable outcome (>=50% pain reduction) was observed in 67.5% of patients, with the best outcome in BPI-related pain. In multivariate analysis, injury of the spinal nerve root (root avulsion or injury) was significantly associated with good average pain relief (OR, 5.8; 95% CI, 1.2 27.5; p = 0.026) and pain freedom (OR, 5.0; 95% CI, 1.12-22.30; p = 0.035). Electrical pain (OR, 6.49; 95% CI, 1.20-35.19; p = 0.030) and lower number of painful dermatomes (OR, 1.30; 95% CI, 1.01-1.67; p = 0.039) were significantly associated with good maximal pain relief. CONCLUSIONS: MDT is an effective procedure for treatment of intractable pain in well-selected patients, particularly in cases with brachial plexus avulsion pain. Injury of the spinal nerve root (brachial plexus avulsion and cauda equina injury) was associated with good average pain relief and pain freedom, and electrical pain and lower number of painful dermatomes were associated with good maximal pain relief. The results are useful in the selection of candidates for DREZotomy and prediction of surgical outcome. PMID- 28993995 TI - PI3K/Akt and ERK/MAPK Signaling Promote Different Aspects of Neuron Survival and Axonal Regrowth Following Rat Facial Nerve Axotomy. AB - The ERK/MAPK and PI3K/Akt signaling pathways play important role in neuronal survival and axonal regeneration after peripheral nerve injury. However, the relative importance and degree of functional overlap of the two pathways are still debated due to lack of in-vivo data. We used rats which underwent a facial nerve axotomy, and examined subsequent ERK/MAPK and PI3K/Akt signaling activity by quantifying phosphorylation of ERK and Akt. We also assessed the survival rate of facial neurons, number of regenerated axons, and the length of axonal regrowth in axotomized animals treated with an inhibitor of ERK/MAPK (U0126) or PI3K/Akt (LY294002) phosphorylation, or with vehicle. Axotomy increased phosphorylation of ERK and Akt in the facial nucleus 7 days after injury. The inhibition of ERK phosphorylation significantly reduced the length of regenerated axons, but not the other parameters. Inhibition of Akt phosphorylation significantly reduced the survival rate of facial neurons and the number of new axons, as well as the length of regenerated axons. The results indicate that facial nerve injury activates the ERK/MAPK and PI3K/Akt signaling pathways in the facial nerve nucleus and its axons. However, the pathways promoted aspects of regeneration with only slight overlap: PI3K/Akt signaling improved the survival of neurons, as well as axonal growth and branching, whereas ERK/MAPK signaling promoted only axonal extension. PMID- 28993996 TI - Toward multi-day-ahead forecasting of suspended sediment concentration using ensemble models. AB - This study explores two ideas to made an improvement on the artificial neural network (ANN)-based models for suspended sediment forecasting in several time steps ahead. In this regard, both observed and forecasted time series are incorporated as input variables of the models when applied for more than one lead time. Secondly, least-square ensemble models employing multiple wavelet-ANN models are developed to increase the performance of the single model. For this purpose, different wavelet families are linked with the ANN model and performance of each model is evaluated using error measures. The Skagit River near Mount Vernon in Washington county is selected as the case study. The daily flow discharge and suspended sediment concentration (SSC) in the current day are considered as input variables to predict suspended sediment concentration in the next day. For more lead times, the input structure is updated by adding the forecast of SSC in the previous time step. Results of this study demonstrate that incorporating both observed and predicted variables in the input structure improves performance of conventional models in which those only employ observed time series as input variables. Moreover, ensemble model developed for each lead time outperforms the best single wavelet-ANN model which indicates superiority of the ensemble model over the other one. Findings of this study reveal that acceptable forecasts of daily suspended sediment concentration up to 3 days in advance can be achieved using the proposed methodology. PMID- 28993997 TI - Evaluation of the prognostic factors in patients with pT3N0 or pT1N2-3 gastric cancer: a single institutional retrospective cohort study. AB - PURPOSE: The impact of adjuvant chemotherapy on the survival of patients with the pT3N0/pT1N2-3 subset of Stage II gastric cancer is unclear. The aim of this study was to evaluate the survival rate of pT3N0/pT1N2-3 patients who were treated by surgery alone and to identify a high-risk group within this cohort. METHODS: A total of 258 patients with pT3N0/pT1N2-3 gastric cancer who underwent gastrectomy alone in our hospital between January 1992 and December 2012 were enrolled in the present study. Their medical records were retrospectively reviewed to evaluate the survival rates and investigate prognostic factors. RESULTS: The 3- and 5-year recurrence-free survival rates of this cohort were 84 and 80%, respectively. The 3- and 5-year overall survival rates were 89 and 83%, respectively. A multivariate analysis revealed that pathological venous infiltration was an independent prognostic factor. The survival of patients with pathological venous infiltration was significantly worse than that of those without (5-year recurrence-free survival, 75 vs. 90%, p = 0.0005; 5-year overall survival, 78 vs. 91%, p = 0.0062). CONCLUSIONS: The prognosis of pT3N0/pT1N2-3 gastric cancer patients treated by surgery alone was relatively good; however, patients with pathological vessel infiltration may be at high risk of recurrence and could be candidates for adjuvant chemotherapy. PMID- 28993998 TI - Lithocholic bile acid inhibits lipogenesis and induces apoptosis in breast cancer cells. AB - BACKGROUND: It has amply been documented that mammary tumor cells may exhibit an increased lipogenesis. Biliary acids are currently recognized as signaling molecules in the intestine, in addition to their classical roles in the digestion and absorption of lipids. The aim of our study was to evaluate the impact of lithocholic acid (LCA) on the lipogenesis of breast cancer cells. The putative cytotoxic effects of LCA on these cells were also examined. METHODS: The effects of LCA on breast cancer-derived MCF-7 and MDA-MB-231 cells were studied using MTT viability assays, Annexin-FITC and Akt phosphorylation assays to evaluate anti proliferative and pro-apoptotic properties, qRT-PCR and Western blotting assays to assess the expression of the bile acid receptor TGR5 and the estrogen receptor ERalpha, and genes and proteins involved in apoptosis (Bax, Bcl-2, p53) and lipogenesis (SREBP-1c, FASN, ACACA). Intracellular lipid droplets were visualized using Oil Red O staining. RESULTS: We found that LCA induces TGR5 expression and exhibits anti-proliferative and pro-apoptotic effects in MCF-7 and MDA-MB-231 cells. Also, an increase in pro-apoptotic p53 protein expression and a decrease in anti-apoptotic Bcl-2 protein expression were observed after LCA treatment of MCF-7 cells. In addition, we found that LCA reduced Akt phosphorylation in MCF-7 cells, but not in MDA-MB-231 cells. We also noted that LCA reduced the expression of SREBP-1c, FASN and ACACA in both breast cancer-derived cell lines and that cells treated with LCA contained low numbers of lipid droplets compared to untreated control cells. Finally, a decrease in ERalpha expression was observed in MCF-7 cells treated with LCA. CONCLUSIONS: Our data suggest a potential therapeutic role of lithocholic acid in breast cancer cells through a reversion of lipid metabolism deregulation. PMID- 28993999 TI - Polybrominated diphenyl ethers (PBDEs) in background air around the Aegean: implications for phase partitioning and size distribution. AB - The occurrence and atmospheric behavior of tri- to deca-polybrominated diphenyl ethers (PBDEs) were investigated during a 2-week campaign concurrently conducted in July 2012 at four background sites around the Aegean Sea. The study focused on the gas/particle (G/P) partitioning at three sites (Ag. Paraskevi/central Greece/suburban, Finokalia/southern Greece/remote coastal, and Urla/Turkey/rural coastal) and on the size distribution at two sites (Neochorouda/northern Greece/rural inland and Finokalia/southern Greece/remote coastal). The lowest mean total (G + P) concentrations of ?7PBDE (BDE-28, BDE-47, BDE-66, BDE-99, BDE 100, BDE-153, BDE-154) and BDE-209 (0.81 and 0.95 pg m-3, respectively) were found at the remote site Finokalia. Partitioning coefficients, K P, were calculated, and their linear relationships with ambient temperature and the physicochemical properties of the analyzed PBDE congeners, i.e., the subcooled liquid pressure (P L degrees ) and the octanol-air partition coefficient (K OA), were investigated. The equilibrium adsorption (P L degrees -based) and absorption (K OA-based) models, as well as a steady-state absorption model including an equilibrium and a non-equilibrium term, both being functions of log K OA, were used to predict the fraction Phi of PBDEs associated with the particle phase. The steady-state model proved to be superior to predict G/P partitioning of BDE-209. The distribution of particle-bound PBDEs across size fractions < 0.95, 0.95-1.5, 1.5-3.0, 3.0-7.2, and > 7.2 MUm indicated a positive correlation between the mass median aerodynamic diameter and log P L degrees for the less brominated congeners, whereas a negative correlation was observed for the high brominated congeners. The potential source regions of PBDEs were acknowledged as a combination of long-range transport with short-distance sources. PMID- 28994000 TI - Fungal Olecranon Bursitis in an Immunocompetent Patient by Knoxdaviesia dimorphospora sp. nov.: Case Report and Review. AB - Bursitis is a common medical condition that can occur either with or without infection. We present a case of fungal olecranon bursitis in an immunocompetent individual caused by the new species Knoxdaviesia dimorphospora. It is a dematiaceous filamentous fungus characterized by the production of two different conidia: hyaline and cylindrical, which rise up from phialidic conidiogenous cells located in the upper part of differentiated and unbranched conidiophores, and pale brown and ellipsoidal conidia produced by phialidic conidiogenous cells which are born directly on hyphae. In addition to its morphological peculiarities, the novelty of the fungus was confirmed by sequence analysis of the internal transcribed spacer (ITS) regions and D1/D2 domains of the 28S of the nuclear rRNA gene. The fungal infection was confirmed by cytological examination and repeated cultures. The infection was resolved by surgical debridement and drainage, and the patient presented a complete functional recovery 3 months later. The in vitro antifungal susceptibility to this new human opportunist is provided, terbinafine being the drug with the most potent activity. PMID- 28994001 TI - Comparison Between Etest and Broth Microdilution Methods for Testing Itraconazole Resistant Aspergillus fumigatus Susceptibility to Antifungal Combinations. AB - The checkerboard broth microdilution assay (BMD) is the most frequently used method for the in vitro evaluation of drug combinations. However, its use to evaluate the effect of antifungal drugs on filamentous fungi is sometimes associated with endpoint-reading difficulties, and different degrees of interaction are assigned to the same drug combination. We evaluated combinations of the azoles, itraconazole, posaconazole, and voriconazole, with the echinocandins, anidulafungin, caspofungin, and micafungin, against 15 itraconazole-resistant Aspergillus fumigatus clinical strains via the checkerboard BMD and Etest assay. Readings after 24 and 48 h, considering the two reading endpoints, the minimum inhibitory concentration (MIC) and minimum effective concentration (MEC), were performed for both methods. Our results showed that the correlation coefficients between the BMD and Etest methods were quite diverse to the drug combinations tested. The highest correlation coefficients of the Etest with the BMD assays (MEC and MIC reading) were the Etest-MIC reading at 24 h and the Etest-MEC reading at 48 h. Improvements in experimental conditions may increase the correlation between the two methods and ensure that Etest assay can be safely used in the evaluation of antifungal combinations against Aspergillus species. PMID- 28994002 TI - Medical Pluralism in the Use of Sobadores among Mexican Immigrants to North Carolina. AB - Mexican immigrants have a rich history of traditional healers. This analysis describes the conditions for which Mexican immigrants seek treatment from sobadores, and delineates factors that influence seeking treatment from a sobador or a biomedical doctor. This systematic qualitative analysis uses interview data collected with 24 adult Mexican immigrants to North Carolina who had been treated by a sobador in the previous 2 years. Immigrants are engaged in medical pluralism, seeking care from sobadores and biomedical doctors based on the complaint and patient's age. Using a hierarchy of resort, adults seek treatment from sobadores for musculoskeletal pain not involving a fracture. Doctors are first consulted when treating children; sobadores are consulted if doctors do not provide culturally appropriate treatment. Mexican immigrants seek care that addresses their culturally determined health concerns. The need to improve access to culturally competent biomedical health care for vulnerable immigrant populations continues. PMID- 28994003 TI - Muscarinic Acetylcholine Receptors Potentiate 5'-Adenosine Monophosphate Activated Protein Kinase Stimulation and Glucose Uptake Triggered by Thapsigargin Induced Store-Operated Ca2+ Entry in Human Neuroblastoma Cells. AB - The 5'-adenosine monophosphate-activated protein kinase (AMPK) is a key regulator of the cellular energy metabolism and may induce either cell survival or death. We previously reported that in SH-SY5Y human neuroblastoma cells stimulation of muscarinic acetylcholine receptors (mAChRs) activate AMPK by triggering store operated Ca2+ entry (SOCE). However, whether mAChRs may control AMPK activity by regulating additional mechanisms beyond SOCE remains to be investigated. In the present study we examined the effects of mAChRs on AMPK when SOCE was induced by the sarco-endoplasmic reticulum Ca2+-ATPase inhibitor thapsigargin. We found that in SH-SY5Y cells depleted of Ca2+ by thapsigargin, the re-addition Ca2+ to the medium stimulated AMPK phosphorylation at Thr172, which is required for full kinase activity. This response occurred through SOCE, as it was blocked by either the SOCE modulator 2-aminoethoxydiphephenyl borate, knockdown of the SOCE molecular component STIM1, or inhibition of Ca2+/calmodulin (CaM)-dependent protein kinase kinase beta (CaMKKbeta). In thapsigargin-pretreated cells, stimulation of pharmacologically defined M3 mAChRs potentiated SOCE-induced AMPK activation. This potentiation did not involve an increased Ca2+ influx, but was associated with CaM mobilization from membrane to cytosol, increased CaM/CaMKKbeta interaction, and enhanced CaMKK stimulation by thapsigargin-induced SOCE. In thapsigargin-pretreated cells Ca2+ re-addition stimulated glucose uptake and increased the membrane expression of the glucose transporter GLUT1. Both responses were significantly potentiated by mAChRs. These data indicate that in human neuroblastoma cells mAChRs up-regulate AMPK and the downstream glucose uptake by triggering not only SOCE but also CaM translocation and enhanced formation of active CaM/CaMKKbeta complexes. PMID- 28994004 TI - Advantages of 18F FDG-PET/CT over Conventional Staging for Sarcoma Patients. AB - The effective management of patients with sarcomas requires accurate diagnosis and staging. Imaging, such as ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI) are the most freqently used methods for the detection of the lesion location, size, morphology and structural changes to adjacent tissues; however, these modalities provide little information about tumour biology. MRI is a robust and useful modality in tumour staging of sarcomas, however metabolic-fluorodeoxyglucose positron emission tomography/ computer tomography (18F-FDG PET/CT) provides greater accuracy to overall staging in combination with MRI [1]. The advantages of 18F-FDG PET/CT method compared with CT and MRI is that it provides a whole body imaging, maps the viability of the tumour or the metabolic activity of the tissue. Additionally, PET detects the most agressive part of the tumour, demonstrates the biological behaviour of the tumour and therefore has a predictive value. Little data ara available on the role of 18F-FDG PET/CT in the management of sarcomas. The present manuscript aims to provide a review of the major indications of 18F-FDG PET/CT for diagnosis, staging, restaging and monitoring response to therapy and to compare its usefulness with the conventional imaging modalities in the management of patients with sarcomas. PMID- 28994005 TI - Characterisation of human induced pluripotent stem cell-derived endothelial cells under shear stress using an easy-to-use microfluidic cell culture system. AB - Induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) can contribute to elucidating the pathogenesis of heart and vascular diseases and developing their treatments. Their precise characteristics in fluid flow however remain unclear. Therefore, the aim of the present study is to characterise these features. We cultured three types of ECs in a microfluidic culture system: commercially available human iPS-ECs, human umbilical vein endothelial cells (HUVECs) and human umbilical artery endothelial cells (HUAECs). We then examined the mRNA expression levels of endothelial marker gene cluster of differentiation 31 (CD31), fit-related receptor tyrosine kinase (Flk-1), and the smooth muscle marker gene smooth muscle alpha-actin, and investigated changes in plasminogen activator inhibitor-1 (PAI-1) secretion and intracellular F-actin arrangement following heat stress. We also compared expressions of the arterial and venous marker genes ephrinB2 and EphB4, and the endothelial gap junction genes connexin (Cx) 37, 40, and 43 under fluidic shear stress to determine their arterial or venous characteristics. We found that iPS-ECs had similar endothelial marker gene expressions and exhibited similar increases in PAI-1 secretion under heat stress as HUVECs and HUAECs. In addition, F-actin arrangement in iPSC-ECs also responded to heat stress, as previously reported. However, they had different expression patterns of arterial and venous marker genes and Cx genes under different fluidic shear stress levels, showing that iPSC-ECs exhibit different characteristics from arterial and venous ECs. This microfluidic culture system equipped with variable shear stress control will provide an easy-to-use assay tool to examine characteristics of iPS-ECs generated by different protocols in various laboratories and contribute to basic and applied biomedical researches on iPS ECs. PMID- 28994006 TI - Isolation and complete genome sequence of Halorientalis hydrocarbonoclasticus sp. nov., a hydrocarbon-degrading haloarchaeon. AB - Bioremediation in hypersaline environments is particularly challenging since the microbes that tolerate such harsh environments and degrade pollutants are quite scarce. Haloarchaea, however, due to their inherent ability to grow at high salt concentrations, hold great promise for remediating the contaminated hypersaline sites. This study aimed to isolate and characterize novel haloarchaeal strains with potentials in hydrocarbon degradation. A haloarchaeal strain IM1011 was isolated from Changlu Tanggu saltern near Da Gang Oilfield in Tianjin (China) by enrichment culture in hypersaline medium containing hexadecane. It could degrade 57 +/- 5.2% hexadecane (5 g/L) in the presence of 3.6 M NaCl at 37 degrees C within 24 days. To get further insights into the mechanisms of petroleum hydrocarbon degradation in haloarchaea, complete genome (3,778,989 bp) of IM1011 was sequenced. Phylogenetic analysis of 16S rRNA gene, RNA polymerase beta subunit (rpoB') gene and of the complete genome suggested IM1011 to be a new species in Halorientalis genus, and the name Halorientalis hydrocarbonoclasticus sp. nov., is proposed. Notably, with insights from the IM1011 genome sequence, the involvement of diverse alkane hydroxylase enzymes and an intact beta oxidation pathway in hexadecane biodegradation was predicted. This is the first hexadecane-degrading strain from Halorientalis genus, of which the genome sequence information would be helpful for further dissecting the hydrocarbon degradation by haloarchaea and for their application in bioremediation of oil polluted hypersaline environments. PMID- 28994007 TI - Impact of Moringa oleifera seed aqueous extract on some biological, biochemical, and histological aspects of Biomphalaria alexandrina snails. AB - Schistosomiasis is one of the neglected tropical diseases. It is a snail-borne trematode infection, and Biomphalaria alexandrina snails are the intermediate host of Schistosoma mansoni in Egypt. The objective of this study is to evaluate the molluscicidal activity of the aqueous seed extract of Moringa oleifera against B. alexandrina snails. The results showed that this aqueous extract was lethal for B. alexandrina snails (LC50 0.27 g/l; LC90 0.41 g/l). Exposure of snails to the sublethal concentrations of this aqueous extract caused a considerable reduction in survival rates and hatchability rates of eggs of these snails. Moreover, it negatively affected some biochemical aspects, where it increased the levels of transaminases (ALT and AST), while it decreased the concentrations of total protein, albumin, and globulin concentration. Histological examinations of the digestive gland of snails exposed to the sublethal concentrations of aqueous seed extract of M. oleifera revealed severe damage in the digestive cells, where they lost their tips and some were degenerated, while the secretory cells increased in number. Regarding the hermaphrodite gland, there were losses of connective tissues and irregular sperms, and the eggs were degenerated. These findings prove the potent activity of aqueous seed extract of M. oleifera against the intermediate hosts of Schistosoma mansoni and provide a considerable scope in exploiting local indigenous resources for snails' molluscicidal agents. PMID- 28994008 TI - How Do Hunter-Gatherer Children Learn Subsistence Skills? : A Meta-Ethnographic Review. AB - Hunting and gathering is, evolutionarily, the defining subsistence strategy of our species. Studying how children learn foraging skills can, therefore, provide us with key data to test theories about the evolution of human life history, cognition, and social behavior. Modern foragers, with their vast cultural and environmental diversity, have mostly been studied individually. However, cross cultural studies allow us to extrapolate forager-wide trends in how, when, and from whom hunter-gatherer children learn their subsistence skills. We perform a meta-ethnography, which allows us to systematically extract, summarize, and compare both quantitative and qualitative literature. We found 58 publications focusing on learning subsistence skills. Learning begins early in infancy, when parents take children on foraging expeditions and give them toy versions of tools. In early and middle childhood, children transition into the multi-age playgroup, where they learn skills through play, observation, and participation. By the end of middle childhood, most children are proficient food collectors. However, it is not until adolescence that adults (not necessarily parents) begin directly teaching children complex skills such as hunting and complex tool manufacture. Adolescents seek to learn innovations from adults, but they themselves do not innovate. These findings support predictive models that find social learning should occur before individual learning. Furthermore, these results show that teaching does indeed exist in hunter-gatherer societies. And, finally, though children are competent foragers by late childhood, learning to extract more complex resources, such as hunting large game, takes a lifetime. PMID- 28994009 TI - Blood cadmium levels associated with short distant metastasis-free survival time in invasive breast cancer. AB - Distant metastasis is strongly associated with poor prognosis of breast cancer. Cadmium (Cd) exposure was previously found associated with breast cancer incidence. We explored the associations of blood cadmium levels (BCLs) and clinicopathologic characteristics with invasive breast cancer distant metastasis. Blood samples were collected and analyzed for BCLs by graphite-furnace atomic absorption spectrometry. Clinicopathologic characteristics, including basic clinical information and tumor characteristics, were obtained from medical records. Breast cancer distant metastasis-free survival (DMFS) time was calculated at follow-up. The associations of BCLs and clinicopathologic characteristics with DMFS time were examined by Kaplan-Meier method and Cox regression analysis, and associations between BCLs and tumor characteristics were also explored. Blood Cd level was positively associated with distant metastasis, clinical stage, BMI, and age. On univariate analysis, older age at diagnosis, family history of breast cancer, high N classification and clinical stage, positivity for human epidermal growth factor receptor 2, and high BCLs were associated with short DMFS time. On multivariate analysis model, older age at diagnosis, family history of breast cancer, high N classification, and BCLs were predictors for breast cancer distant metastasis. BCLs were a risk factor for short DMFS time of invasive breast cancer. BCLs and some clinicopathologic factors affect breast cancer distant metastasis, which needs further epidemiological and experimental studies to confirm. PMID- 28994010 TI - Parsing the neural correlates of anxious apprehension and anxious arousal in the grey-matter of healthy youth. AB - Neuroscientific and psychological research posits that there are two transdiagnostic facets of anxiety: anxious arousal and anxious apprehension. Though these two facets of anxiety are distinct, they are often subsumed into one domain (e.g., trait anxiety). The primary goal of the current study was to delineate the relationship between anxious arousal and cortical thickness versus the relationship between anxious apprehension and cortical thickness in a sample of typically functioning youth. The secondary aim was to determine where in the brain cortical thickness significantly correlated with both components of anxiety. Results indicated that the right anterior insula has a stronger relationship to anxious arousal, whereas the dorsolateral prefrontal cortex and left anterior insula were found to correlate with both anxious arousal and apprehension. We also observed volumetric differences in the amygdala and hippocampus between anxious arousal and anxious apprehension. Whereas anxious arousal, but not apprehension, predicted left amygdala volume, anxious apprehension, but not arousal, predicted right hippocampal volume. These findings demonstrated that there are both differences and similarities in the neural regions that contribute to independent facets of anxiety. Results are discussed in terms of previous findings from the affective and developmental cognitive neurosciences. PMID- 28994011 TI - Vanadium(V) complexes with hydrazides and their spectroscopic and biological properties. AB - The present study explores the synthesis and inhibitory potential of vanadium(V) complexes of hydrazides (1c-12c) against oxidative enzymes including xanthine oxidase and lipoxygenase (LOX). In addition, non-enzymatic radical scavenging activities of these complexes were also determined. On the basis of spectral, elemental and physical data, synthesized vanadium(V) complexes are tentatively assigned to have an octahedral geometry with two hydrazide ligands and two oxo groups forming a negatively charged sphere complex with ammonium as counter ion. This is further verified by the conductivity studies of the complexes. Results show that hydrazide ligands (1-12) and their respective vanadium(V) complexes (1c 12c) posses scavenging and inhibition potential against DPPH and LOX, respectively. However, contrary to that uncoordinated ligands showed no activity against nitric oxide, superoxide and xanthine oxidase whereas their complexes showed varying degree of activity. These studies indicate that geometry of complex, nature and position of substituent groups play a vital role in scavenging and inhibition potential of these compounds. PMID- 28994012 TI - Comparative In Vitro Toxicity Evaluation of Heavy Metals (Lead, Cadmium, Arsenic, and Methylmercury) on HT-22 Hippocampal Cell Line. AB - Heavy metals are considered some of the most toxic environmental pollutants. Exposure to heavy metals including lead (Pb), cadmium (Cd), arsenic (As), and methyl mercury (MeHg) has long been known to cause damage to human health. Many recent studies have supported the hippocampus as the major target for these four metals for inflicting cognitive dysfunction. In the present study, we proposed hippocampal relevant in vitro toxicity of Pb, Cd, As, and MeHg in HT-22 cell line. This study reports, initially, cytotoxic effects in acute, subchronic, chronic exposures. We further investigated the mechanistic potency of DNA damage and apoptosis damage with the observed cytotoxicity. The genotoxicity and apoptosis were measured by using the comet assay, annexin-V FTIC / propidium iodide (PI) assay, respectively. The results of cytotoxicity assay clearly demonstrated significant concentration and time-dependent effects on HT-22 cell line. The genotoxic and apoptosis effects also concentration-dependent fashion with respect to their potency in the range of IC10-IC30, maximal level of damage observed in MeHg. In conclusion, the obtained result suggests concentration and potency-dependent response; the maximal level of toxicity was observed in MeHg. These novel findings support that Pb, Cd, As, and MeHg induce cytotoxic, genotoxic, and apoptotic effects on HT-22 cells in potency-dependent manner; MeHg> As> Cd> Pb. Therefore, the toxicity of Pb, Cd, As, and MeHg could be useful for knowing the common underlying molecular mechanism, and also for estimating the mixture impacts on HT-22 cell line. PMID- 28994013 TI - Outcomes, safety, and feasibility of video-assisted thoracic surgery in lung cancer patients on hemodialysis: a case series. AB - OBJECTIVE: The rate of surgical resection of lung cancer in patients on hemodialysis is expected to increase due to the development of hemodialysis, improved diagnosis of lung cancer, and increases in the number and age of patients. However, studies assessing outcomes of lung resection in these patients are limited. In this retrospective case series, we investigated the safety and efficacy of video-assisted thoracic surgery (VATS) for lobectomy or segmentectomy for lung cancer in patients on hemodialysis. METHODS: Between January 2010 and January 2017, lobectomy or segmentectomy using VATS was performed for seven lung cancer cases in six patients receiving hemodialysis at our institution. There were two female and five male patients, with a median age of 61 years (range 53 76 years). Six patients underwent lobectomy, and segmentectomy and wedge resection were performed in each one case, respectively; systematic mediastinal lymph node dissection (ND2a-2) was performed in six patients. RESULTS: There were no perioperative deaths in this case series. Median recurrence-free and overall survival rates were 20 months (range 3-82 months) and 31 months (range 3-82 months), respectively. CONCLUSIONS: Video-assisted thoracic surgery (VATS) is a safe and effective procedure for resection of lung cancer in hemodialysis patients and should be considered after accurate determination of surgical indications and careful perioperative management. PMID- 28994014 TI - Intra- and inter-specific variations in chitin in lichens along a N-deposition gradient. AB - The mechanisms of nitrogen (N) tolerance in lichens are not yet fully understood. Here, we investigated how the increase of chitin content is related with N excess at inter- and intra-specific levels, by using species with differing ecological N tolerances (the tolerant Xanthoria parietina and Parmotrema hypoleucinum and the sensitive Evernia prunastri and Usnea sp.) and thalli of X. parietina and P. hypoleucinum from sites with different availabilities of N of agricultural origin (livestock), as confirmed by lichen N content and delta15N. Nitrogen, chitin (N containing compound), and ergosterol contents were measured in lichen thalli. Nitrogen and chitin contents were higher in tolerant species than those in sensitive ones (inter-specific level) and in thalli collected from the N-polluted site than in thalli from the clean site (intra-specific level). We suggest that chitin contributes to N stress tolerance in lichens, and that excess N can be partially stored as chitin (non-toxic form) in the cell walls of tolerant species. PMID- 28994015 TI - Exploring standardized precipitation evapotranspiration index for drought assessment in Bangladesh. AB - Drought is a critical issue, and it has a pressing, negative impact on agriculture, ecosystems, livelihoods, food security, and sustainability. The problem has been studied globally, but its regional or even local dimension is sometimes overlooked. Local-level drought assessment is necessary for developing adaptation and mitigation strategies for that particular region. Keeping this in understanding, an attempt was made to create a detailed assessment of drought characteristics at the local scale in Bangladesh. Standardized precipitation evapotranspiration (SPEI) is a new drought index that mainly considers the rainfall and evapotranspiration data set. Globally, SPEI has become a useful drought index, but its local scale application is not common. SPEIbase (0.5 degrees grid data) for 110 years (1901-2011) was utilized to overcome the lack of long-term climate data in Bangladesh. Available weather data (1955-2011) from Bangladesh Meteorology Department (BMD) were analyzed to calculate SPEIweather station using the SPEI calculator. The drivers for climate change-induced droughts were characterized by residual temperature and residual rainfall data from different BMD stations. Grid data (SPEIbase) of 26 stations of BMD were used for drought mapping. The findings revealed that the frequency and intensity of drought are higher in the northwestern part of the country which makes it vulnerable to both extreme and severe droughts. Based on the results, the SPEI based drought intensity and frequency analyses were carried out, emphasizing Rangpur (northwest region) as a hot spot, to get an insight of drought assessment in Bangladesh. The findings of this study revealed that SPEI could be a valuable tool to understand the evolution and evaluation of the drought induced by climate change in the country. The study also justified the immediate need for drought risk reduction strategies that should lead to relevant policy formulations and agricultural innovations for developing drought adaptation, mitigation, and resilience mechanisms in Bangladesh. PMID- 28994016 TI - Cardiopulmonary Manifestations of Collagen Vascular Diseases. AB - PURPOSE OF REVIEW: The study aimed to illustrate the cardiopulmonary findings of the following collagen vascular diseases on cross-sectional imaging: rheumatoid arthritis, scleroderma (progressive systemic sclerosis), systemic lupus erythematosus, the inflammatory myopathies (polymyositis/dermatomyositis), and Sjogren's syndrome. RECENT FINDINGS: Although collagen vascular diseases can affect any part of the body, interstitial lung disease and pulmonary hypertension are the two most important cardiopulmonary complications and are responsible for the majority of morbidity and mortality in this patient population. Interstitial pneumonia with autoimmune features (IPAF) is a newly described entity that encompasses interstitial lung disease in patients with clinical, serologic, or morphologic features suggestive of but not diagnostic of collagen vascular disease; these patients are thought to have better outcomes than idiopathic interstitial pneumonias. Interstitial lung disease and pulmonary hypertension determine the prognosis in collagen vascular disease patients. IPAF is a new term to label patients with possible collagen vascular disease-related interstitial lung disease. Collagen vascular disease patients are at increased risk for various malignancies. PMID- 28994017 TI - Comparison of fluorine-18 fluorodeoxyglucose positron emission tomography with gallium-67 scintigraphy in the initial clinical staging of diffuse large B-cell lymphoma. AB - Fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) has been recommended as a complementary tool for the staging of various malignancies, including malignant lymphoma. PET findings often shift patients to higher stages and may affect treatment outcomes. In this study, we retrospectively compared staging and treatment outcomes of newly diagnosed diffuse large B-cell lymphoma (DLBCL) assessed by PET (n = 153) or gallium-67 scintigraphy (Ga) (n = 95). In total, Ga upstaged two (2.1%) of 95 patients, whereas PET upstaged 13 (8.5%) of 153 patients. Bone/bone marrow (15 vs. 4%, P = 0.01) and muscle lesion (5 vs. 0%, P = 0.03) were identified more frequently in the PET group than in the Ga group. The estimated 3-year overall and progression-free survival rates did not differ significantly in the two groups at any stage. However, patients with stage III disease tended to have better progression-free survival in the PET group than in the Ga group [92.3 (95% CI 56.6-98.9%) vs. 58.3% (95% CI 27.0-80.1%), P = 0.086]. These results suggest that PET has a greater potential in detecting musculoskeletal lesions of DLBCL as extranodal lesions than Ga, and may contribute to the optimal staging. PMID- 28994018 TI - Memory CD4+ T cell subsets in tumor draining lymph nodes of breast cancer patients: A focus on T stem cell memory cells. AB - BACKGROUND: The compartments of memory T cells play a fundamental role in the immune system by substantiating specific and acquired immunity. A new subset of memory cells, T stem cell memory (TSCM) cells, with stem cell-like properties, a high capacity to proliferate, a long survival, and an ability to differentiate into all effector and memory cells has recently been introduced. In the present study, we aimed to determine the frequency of CD4+ TSCM and other T memory cell subsets in tumor draining lymph nodes of breast cancer patients. MATERIALS AND METHODS: Mononuclear cells were obtained from axillary lymph nodes of 52 untreated patients with breast cancer (BC) and stained with fluorochrome conjugated anti-CD4, -CCR7, -CD45RO and -CD95 antibodies to detect different subtypes of memory cells in CD4+ lymphocyte populations. Data were acquired using a four-color FACSCalibur flow cytometer and analyzed using CellQuest Pro software. RESULTS: We found that >70% of CD4+ lymphocytes in draining lymph nodes of BC patients exhibited a memory phenotype of which 7.04 +/- 1.04% had a TSCM phenotype (CD4+CCR7+CD45RO-CD95+). The frequency of TSCM cells was significantly higher in tumor positive lymph nodes compared to tumor negative lymph nodes (p = 0.026) as well as among those patients who had at least one affected lymph node (p = 0.012). Moreover, we found that the total frequency of central memory T cells (TCM) with a low expression of CD45RO was significantly higher among these patients. The percentage of CD45ROLow TCM cells was also found to increase with tumor progression from stage I to stage III (p = 0.020). On the other hand, we found that the percentage of CD95Hi effector memory T cells (TEM) was significantly decreased in involved lymph nodes (p = 0.009). CONCLUSION: Our data suggest that following long-term exposure to putative tumor antigens, TSCM cells proliferate to generate a pool of committed memory and effector T cells. As the tumor progresses, the immunosuppressive milieu induced by tumor cells may slow down the differentiation of CD45ROLow TCM cells to more functional sub populations. PMID- 28994019 TI - Tempo-spatial dynamics of water quality and its response to river flow in estuary of Taihu Lake based on GOCI imagery. AB - Knowledge of tempo-spatial dynamics of water quality and its response to river flow is important for the management of lake water quality because river discharge associated with rainstorms can be an important source of pollutants to the estuary. Total phosphorus (TP), chlorophyll a (Chl-a), and total suspended matter (TSM) are important indexes of water quality and important factors influencing eutrophication and algal blooms. In this study, remote sensing was used to monitor these indexes to investigate the effects of river discharge on the estuary of Taihu Lake by the largest inflow river which is Chendong River using a total of 136 Geostationary Ocean Color Images (GOCI). In situ datasets collected during the four cruise experiments on Taihu Lake between 2011 and 2015 were used to develop the TP, Chl-a, and TSM inversion models based on simple empirical algorithms: 154 points for TP (mg/L), 114 for Chl-a (MUg/L), and 181 for TSM (mg/L). The spatial and temporal changes of the concentration of the three parameters in the Chendong River estuary were analyzed by combining the GOCI data, the flow of the Chendong River, and meteorological data throughout the year in 2014. The several key findings are as follows: (1) In summer and autumn, TP, Chl-a, and TSM contents were significantly higher than in winter and spring. TP and Chl-a have a few similar distribution characteristics. And organic suspended matter in summer was the main reason for the increase of the TSM concentration. (2) The severe surface erosion in the rivers cannot be ignored; the high erodibility is an important factor in the increase of TP and TSM concentrations in the estuary. The concentration of the water quality parameter showed exponential decay with distance from the shore. The concentration decreased slowly after 12 km and then remained essentially constant. (3) TP content in the Chendong River estuary decreased under steady flow inputs and dramatically increased when the flow became large. The increase in Chl-a content was linked to higher levels of TP and good weather conditions after the rain event. Higher flow rates mainly play a dilution role for the Chl-a concentration. Erosion of the surface soil via rainfall is a major source of TSM to the estuary. This paper firstly analyzes tempo-spatial dynamics of water quality and its response to river flow in estuary of Taihu Lake, helps to further understand the impact of river input on lake water quality, and is important for lake eutrophication. PMID- 28994020 TI - Vitamin D and the Skin: An Update for Dermatologists. AB - Vitamin D plays a key role in skeletal and cardiovascular disorders, cancers, central nervous system diseases, reproductive diseases, infections, and autoimmune and dermatological disorders. The two main sources of vitamin D are sun exposure and oral intake, including vitamin D supplementation and dietary intake. Multiple factors are linked to vitamin D status, such as Fitzpatrick skin type, sex, body mass index, physical activity, alcohol intake, and vitamin D receptor polymorphisms. Patients with photosensitive disorders tend to avoid sun exposure, and this practice, along with photoprotection, can put this category of patients at risk for vitamin D deficiency. Maintaining a vitamin D serum concentration within normal levels is warranted in atopic dermatitis, psoriasis, vitiligo, polymorphous light eruption, mycosis fungoides, alopecia areata, systemic lupus erythematosus, and melanoma patients. The potential determinants of vitamin D status, as well as the benefits and risks of vitamin D (with a special focus on the skin), will be discussed in this article. PMID- 28994021 TI - Radial head prosthesis: surgical tips and tricks. AB - Radial head prostheses (RHP) have been developed to decrease the complications rate following a radial head resection surgery. The aim of the RHP is to replicate the physiological radiocapitellar tracking, reproducing the mechanical function of the native radial head: to stabilize the elbow and to shear the forces passing through the elbow along with the other stabilizers. The currently used RHP models try to achieve this target with three different prosthesis' strategies: (a) loose fit stem, (b) bipolar radial head or (c) anatomical radial head. Even if the radial head fixation is the preferred technique in every possible case and the resection can be still considered a possible option, in the last years there has been a growing worldwide consensus in using the radial head replacement in patients with unfixable radial head fractures, especially if associated with complex elbow instability. However, complications after a RHP are not uncommon, and their rate is raising as long as the implants number are increasing. The main difficulties are due to the implantation technique that needs to be performed with the same attention and precision used for the replacement of all the other joints, and to the concurrent treatment of the associated lesions. A personalized postoperative rehabilitation program is essential for obtaining good results and decreasing the complications rate. Concern exists for the young age of the patients that often require a RHP: personal experience and literature analysis suggest that if the clinical and radiographic results are positive after a 6-12-month follow-up, good outcomes can be also expected at a medium- or long-term follow-up. PMID- 28994024 TI - Association of Vitamin B12, Lactate Dehydrogenase, and Regulation of NF-kappaB in the Mitigation of Sodium Arsenite-Induced ROS Generation in Uterine Tissue by Commercially Available Probiotics. AB - Managing arsenic intoxication with conventional metal chelators is a global challenge. The present study demonstrated the therapeutic role of probiotics against arsenic-induced oxidative stress and female reproductive dysfunction. Sodium arsenite-treated (1.0 mg/100 g body weight) Wistar female rats were followed up by a post-treatment of commercially available probiotic mixture in powder form (0.25 mg/100 g body weight) orally. Rats that experienced arsenic ingestion showed a significant lessening in the activities of uterine superoxide dismutase (SOD), catalase activities, and the level of non-protein soluble thiol (NPSH) with a concomitant increase in malondialdehyde (MDA) and conjugated dienes (CD). Exposure to arsenic significantly lowered the levels of vitamin B12 and estradiol. Exposure to arsenic highly expressed the inflammatory marker and transcription factor NF-kappaB. Arsenic-mediated instability of these above parameters was controlled by the probiotics with a rebuilding of better function of anti-oxidant components. Besides its function in regulating endogenous anti oxidant system, probiotics were able to augment the protection against mutagenic uterine DNA-breakage, necrosis, and ovarian-uterine tissue damages in arsenicated rats. PMID- 28994022 TI - Evaluation of epigenetic alterations (mir-126 and mir-155 expression levels) in Mexican children exposed to inorganic arsenic via drinking water. AB - Recently, a great number of epidemiological studies have shown evidence that exposure to inorganic arsenic could have harmful effects on the cardiovascular system of humans. However, the underlying mechanisms through which arsenic induces cardiovascular toxic effects remain unclear. In this regard, epigenetic mechanisms have emerged as a probable connection between environment and disease phenotypes, including cardiovascular diseases. Therefore, this study aimed to evaluate epigenetic changes related to cardiotoxicity (miR-126 and miR-155 expression levels) in children from San Luis Potosi, Mexico exposed to inorganic arsenic. From 2014 to 2015, in a cross-sectional study, children (aged 6-12 years; n = 73) attending public schools at the studied sites were enrolled to take part in this study. Urinary arsenic was used as an exposure biomarker and analyzed by an atomic absorption spectrophotometry technique. On the other hand, miR-126 and miR-155 expression levels were evaluated by qRT-PCR. A mean urinary arsenic level of 30.5 +/- 25.5 MUg/g of creatinine was found. Moreover, the data showed a significant negative association (p < 0.05) between urinary arsenic concentrations and plasma miR-126 levels. However, an association between urinary arsenic concentrations and plasma miR-155 levels was not found (p > 0.05). In this regard, some investigations have shown an association between diminished plasma miR-126 levels and cardiovascular illnesses. The results found in this study are of concern. However, more similar studies including a larger sample size are necessary in order to clarify the real significance of the data. PMID- 28994023 TI - Treatment with pentylenetetrazole (PTZ) and 4-aminopyridine (4-AP) differently affects survival, locomotor activity, and biochemical markers in Drosophila melanogaster. AB - PTZ is a convulsive agent that acts via selective blockage of GABAA receptor channels, whereas 4-AP leads to a convulsive episode via blockage of K+ channels. However, the mechanism(s) by which pentylenetetrazole (PTZ) and 4-aminopyridine (4-AP) cause toxicity to Drosophila melanogaster needs to be properly explored, once it will help in establishing an alternative model for development of proper therapeutic strategies and also to counteract the changes associated with exposure to both epileptic drugs. For the purpose, we investigated the effects of exposure (48 h) to PTZ (60 mM) and/or 4-AP (20 mM) on survival, locomotor performance, and biochemical markers in the body and/or head of flies. 4-AP-fed flies presented a higher incidence of mortality and a worse performance in the open field test as compared to non-treated flies. 4-AP also caused a significant increase in the reactive species (RS) and protein carbonyl (PC) content in the body and head. Also a significant increase in catalase and acetylcholinesterase (AChE) activities was observed in the body. In the same vein, PTZ exposure resulted in a significant increase in RS, thiobarbituric acid reactive substances (TBARS), PC content, and catalase activity in the body. PTZ exposure also caused a significant increase in AChE activity both in body and head. It is important to note that PTZ-treated flies also down-regulated the NRF2 expression. Moreover, both 4AP- and PTZ-fed flies presented a significant decrease in MTT reduction, down-regulation, and inhibition of SOD in body. However, SOD was significantly more active in the head of both 4-AP and PTZ-treated flies. Our findings provide evidence regarding the toxicological potential of both PTZ and/or 4-AP to flies. This model will help in decoding the underlying toxicological mechanisms of the stated drugs. It will also help to properly investigate the therapeutic strategies and to counteract the drastic changes associated with both epileptogenic drugs. PMID- 28994025 TI - Applying the Glenoid Track Concept in the Management of Patients with Anterior Shoulder Instability. AB - PURPOSE OF REVIEW: The purpose of this paper is to evaluate the recent evolution in the treatment of anterior shoulder instability and the dynamic interaction between the glenoid and Hill-Sachs lesion. RECENT FINDINGS: Through the glenoid track concept, glenoid- and humeral-sided bone loss are evolving away from being approached as separate entities. Recent cadaveric studies have validated the glenoid track concept. Moreover, a recent clinical study has demonstrated a much higher rate of failure after arthroscopic Bankart repair for shoulders that were off track. The glenoid track concept is a useful tool in evaluating patients with anterior shoulder instability. Shoulders that are off track may require more than a simple arthroscopic Bankart, and the addition of a remplissage or bony transfer may be considered. PMID- 28994026 TI - Eight Years at the Helm. PMID- 28994027 TI - Management of Glenoid Bone Loss with Anterior Shoulder Instability: Indications and Outcomes. AB - PURPOSE OF REVIEW: Glenoid Bone Loss is a commonly encountered problem in anterior shoulder instability. In this article, we review current techniques for diagnosis, indications and management of glenoid bone loss. RECENT FINDINGS: Multiple bone grafting techniques are available depending on the glenoid defect size including the coracoid, distal clavicle, iliac crest, and allograft distal tibia. Advancement in imaging methods allows for more accurate quantification of bone loss. Indications and techniques are continuing to evolve, and emerging evidence suggests that smaller degrees of bone loss "subcritical" may be best treated with bone grafting. Future directions for innovation and investigation include improved arthroscopic techniques and a refinement of indications for the type of bone grafts and when to indicate a patient of arthroscopic repair versus glenoid bone grafting for smaller degrees of bone loss to ensure successful outcome. PMID- 28994028 TI - Treatment for Degenerative Lumbar Spondylolisthesis: Current Concepts and New Evidence. AB - PURPOSE OF REVIEW: Current guidelines for the optimal treatment degenerative spondylolisthesis are weak and based on limited high-quality evidence. RECENT FINDINGS: There is some moderate evidence that decompression alone may be a feasible treatment with lower surgical morbidity and similar outcomes to fusion when performed in a select population with a low-grade slip. Similarly, addition of interbody fusion may be best suited to a subset of patients with high-grade degenerative spondylolisthesis, although this remains controversial. Minimally invasive techniques are increasingly being utilized for both decompression and fusion surgeries with more and more studies showing similar outcomes and lower postoperative morbidity for patients. This will likely be an area of continued intense research. Finally, the role of spondylolisthesis reduction will likely be determined as further investigation into optimal sagittal balance and spinopelvic parameters is conducted. Future identification of ideal thresholds for sagittal vertical axis and slip angle that will prevent progression and reoperation will play an important role in surgical treatment planning. Current evidence supports surgical treatment of degenerative spondylolisthesis. While posterolateral spinal fusion remains the treatment of choice, the use of interbodies and decompressions without fusion may be efficacious in certain populations. However, additional high-quality evidence is needed, especially in newer areas of practice such as minimally invasive techniques and sagittal balance correction. PMID- 28994030 TI - GeLC-MS: A Sample Preparation Method for Proteomics Analysis of Minimal Amount of Tissue. AB - Application of various proteomics methodologies have been implemented for the global and targeted proteome analysis of many different types of biological samples such as tissue, urine, plasma, serum, blood, and cell lines. Among the aforementioned biological samples, tissue has an exceptional role into clinical research and practice. Disease initiation and progression is usually located at the tissue level of different organs, making the analysis of this material very important for the understanding of the disease pathophysiology. Despite the significant advances in the mass spectrometry instrumentation, tissue proteomics still faces several challenges mainly due to increased sample complexity and heterogeneity. However, the most prominent challenge is attributed to the invasive procedure of tissue sampling which restricts the availability of fresh frozen tissue to minimal amounts and limited number of samples. Application of GeLC-MS sample preparation protocol for tissue proteomics analysis can greatly facilitate making up for these difficulties. In this chapter, a step by step guide for the proteomics analysis of minute amounts of tissue samples using the GeLC-MS sample preparation protocol, as applied by our group in the analysis of multiple different types of tissues (vessels, kidney, bladder, prostate, heart) is provided. PMID- 28994029 TI - Identification of the quinolinedione inhibitor binding site in Cdc25 phosphatase B through docking and molecular dynamics simulations. AB - Cdc25 phosphatase B, a potential target for cancer therapy, is inhibited by a series of quinones. The binding site and mode of quinone inhibitors to Cdc25B remains unclear, whereas this information is important for structure-based drug design. We investigated the potential binding site of NSC663284 [DA3003-1 or 6 chloro-7-(2-morpholin-4-yl-ethylamino)-quinoline-5, 8-dione] through docking and molecular dynamics simulations. Of the two main binding sites suggested by docking, the molecular dynamics simulations only support one site for stable binding of the inhibitor. Binding sites in and near the Cdc25B catalytic site that have been suggested previously do not lead to stable binding in 50 ns molecular dynamics (MD) simulations. In contrast, a shallow pocket between the C terminal helix and the catalytic site provides a favourable binding site that shows high stability. Two similar binding modes featuring protein-inhibitor interactions involving Tyr428, Arg482, Thr547 and Ser549 are identified by clustering analysis of all stable MD trajectories. The relatively flexible C terminal region of Cdc25B contributes to inhibitor binding. The binding mode of NSC663284, identified through MD simulation, likely prevents the binding of protein substrates to Cdc25B. The present results provide useful information for the design of quinone inhibitors and their mechanism of inhibition. PMID- 28994031 TI - Differential Adipose Tissue Proteomics. AB - Differential proteomic analysis (comparative quantitative proteomics) is a robust quantitative technique used to detect and identify the proteome of selected tissues. The expression levels (upregulated vs. downregulated) of proteins in tissue samples that differ by experimental design or anatomic location are determined by a series of assays including (1) 2D difference gel electrophoresis (2D-DiGE), (2) protein spot picking based on a priori thresholds, (3) Mass Spectrometry, and (4) follow-up Western Blot for antibody validation (Chen et al., Mol Cell Proteomics 14:2466-2478, 2015). Differential proteomic analysis is a perfect method for analyzing a heterogeneous tissue such as adipose tissue with a composition spectrum consisting of white to brown adipocytes along with a stromal vascular fraction dependent on anatomical location and inflammation. The adipose tissue proteomic protocol outlined here was successful in identifying differentially expressed proteins both significantly upregulated and downregulated between the experimental and control groups (Shields et al., Pulm Circ 6:586-596, 2016). PMID- 28994032 TI - HLA Class I and Class II-Induced Intracellular Signaling and Molecular Associations in Primary Human Endothelial Cells. AB - The signaling capacity of HLA molecules in vascular cells has been well established. Intracellular signaling and association with the coreceptor integrin beta4 has been well-studied for HLA class I. However, little is known regarding HLA class II intracellular signaling in human endothelial cells. Investigation of HLA class II has been challenging due to the loss of HLA class II expression in cultured primary cells. Herein, we describe methods for inducing expression of endogenous alleles and loci of HLA class II molecules, as well as for studying intracellular signaling. This includes siRNA knockdown of proteins and coimmunoprecipitation of putative coreceptors for HLA in primary human aortic endothelial cells. PMID- 28994033 TI - The effect of simulator fidelity on acquiring non-technical skills: a randomized non-inferiority trial. AB - INTRODUCTION: As simulator fidelity (i.e., realism) increases from low to high, the simulator more closely resembles the real environment, but it also becomes more expensive. It is generally assumed that the use of high-fidelity simulators results in better learning; however, the effect of fidelity on learning non technical skills (NTS) is unknown. This was a non-inferiority trial comparing the efficacy of high- vs low-fidelity simulators on learning NTS. METHODS: Thirty-six postgraduate medical trainees were recruited for the trial. During the pre-test phase, the trainees were randomly assigned to manage a scenario using either a high-fidelity simulator (HFS) or a low-fidelity simulator (LFS), followed by expert debriefing. All trainees then underwent a video recorded post-test scenario on a HFS, and the NTS were assessed between the two groups. The primary outcome was the overall post-test Ottawa Global Rating Scale (OGRS), while controlling for overall pre-test OGRS scores. Non-inferiority between the LFS and HFS was based on a non-inferiority margin of greater than 1. RESULTS: For our primary outcome, the mean (SD) post-test overall OGRS score was not significantly different between the HFS and LFS groups after controlling for pre-test overall OGRS scores [3.8 (0.9) vs 4.0 (0.9), respectively; mean difference, 0.2; 95% confidence interval, -0.4 to 0.8; P = 0.48]. For our secondary outcomes, the post test total OGRS score was not significantly different between the HFS and LFS groups after controlling for pre-test total OGRS scores (P = 0.33). There were significant improvements in mean overall (P = 0.01) and total (P = 0.003) OGRS scores from pre-test to post-test. There were no significant associations between postgraduate year (P = 0.82) and specialty (P = 0.67) on overall OGRS performance. CONCLUSION: This study suggests that low-fidelity simulators are non inferior to the more costly high-fidelity simulators for teaching NTS to postgraduate medical trainees. PMID- 28994034 TI - On the interactions among zinc availability and responses to ozone stress in durum wheat seedlings. AB - Seedlings of durum wheat [Triticum turgidum subsp. durum (Desf.) Husn] were exposed to zinc nutrition and to ozone (O3) in a factorial combination: adequate (+Zn treatment) or no Zn (-Zn) in the nutrient solution, followed by exposure to either ozone-free air (filtered air, FA) or to 150 nL L-1 ozone (O3) for 4 h. Although omitting Zn from the nutrient solution failed to impose a genuine Zn deficiency, -Zn*FA durum wheat seedlings showed a typical deficiency behaviour, i.e. Zn mobilisation from root to shoot. Such inter-organ Zn redistribution, however, did not occur in -Zn*O3 plants. Exposure to each stress singly decreased the activity and the protein amount of foliar plasma membrane H+-ATPase, but not stress combination, which even increased the H+-ATPase expression with respect to control. In the -Zn*O3 plants, moreover, the foliar activities of the plasma membrane-bound NAD(P)H-dependent superoxide synthase and of Cu,Zn-superoxide dismutase, and the transcripts abundance of the luminal binding protein and of the protein disulphide isomerase, were also stimulated. It is proposed that, even in the absence of actual Zn starvation, the perception of deficiency conditions could trigger changes in redox homoeostasis at the plasma membrane level, helpful in compensating an O3-dependent oxidative damage. PMID- 28994035 TI - SurvivorCHESS to increase physical activity in colon cancer survivors: can we get them moving? AB - PURPOSE: This randomized controlled trial evaluated the impact of SurvivorCHESS, an eHealth intervention, on physical activity in colon cancer survivors and to explore the impact of SurvivorCHESS on quality of life and distress. METHODS: This was a two-arm single-blinded multi-site randomized controlled trial comparing a control group to an intervention group receiving a smartphone with the SurvivorCHESS program. RESULTS: Participants using SurvivorCHESS (n = 144) increased their moderate to vigorous physical activities from 19.4 min at baseline to 50 min compared to the control group (n = 140) increasing from 15.5 to 40.3 min at 6 months (p = .083) but was not sustained 3 months after the study ended. No significant differences were found between groups over time for quality of life or distress items. Reports of physical symptoms were greater than other categories for distress items. Patients who had a higher body mass index and number of comorbid conditions were less likely to increase their physical activity. Self-determination theory including autonomous motivation and relatedness was not associated with the outcomes. CONCLUSIONS: Physical activity did increase over time in both groups and was not significantly different with the use of the eHealth intervention, SurvivorCHESS, compared to the control group. The amount of SurvivorCHESS use was not associated with physical activity. IMPLICATIONS FOR CANCER SURVIVORS: Increasing physical activity in colon cancer survivors has the potential to improve quality of life and reduce recurrences. Using smartphone-tracking devices may be useful in helping to change this health behavior. PMID- 28994036 TI - Comparison of 4 different strategies of DAPT after PCI in ACS real world population from a Northern Italy registry. AB - Aim of the study was to compare four different strategies of dual antiplatelet therapy (DAPT) in patients with acute coronary syndromes (ACS) treated with PCI. DAPT with Clopidogrel, Ticagrelor and Prasugrel has proved to be effective in patients with ACS treated with percutaneous coronary intervention (PCI) by reducing major adverse cardiovascular outcomes (MACE). However, the effect of the different strategies in a real-world population deserves further verification. A retrospective analysis of 2404 discharged ACS patients treated with PCI was performed, with a median follow-up of 1 year. The study population was stratified in four drug treatment cohorts: ASA + Clopidogrel (A-C), ASA + Plavix (A-PLx), ASA + Ticagrelor (A-T), ASA + Prasugrel (A-P). We assessed the incidence of net adverse cardiovascular events (NACE): all-cause death, myocardial infarction (MI), target vessel revascularization (TVR), stroke and bleeding during follow up. At 1-year, the use of A-C and A-PLx was associated with the highest cumulative incidence of NACE in comparison with A-T and A-P therapies (respectively 14.8 and 29.6% vs. 9.2 and 6%). This difference was mainly driven by the mortality and TVR outcomes. Considering selection bias and differences in the patients baseline characteristics, the association of A-T and A-P seems to be superior in comparison with a DAPT strategy of A-C and A-PLx in low risk ACS-PCI patients from real world. In our Region the prescription is consistent with guidelines recommendations and Clopidogrel and Plavix are still predominantly used in older patients with more comorbidities, and this could partially explain the inferiority of this association. PMID- 28994039 TI - Utility of Pit-1 Immunostaining in Distinguishing Pituitary Adenomas of Primitive Differentiation from Null Cell Adenomas. AB - Pit-1 immunostaining is not routinely used in the characterization of pituitary adenomas, and its utility in distinguishing adenomas dedicated towards the lactotroph, somatotroph, and thyrotroph lineage from null cell adenomas warrants further evaluation. Pituitary adenomas that were negative for expression of a basic panel of hormonal markers (ACTH, prolactin, and growth hormone) were further evaluated for TSH, SF-1, and Pit-1 expression using a tissue microarray. Among the 147 identified pituitary adenomas that were negative for ACTH, prolactin, growth hormone, and TSH, expression of SF-1 was present in 68 cases (46%). Of the remaining 72 cases with sufficient tissue for further analysis, four were Pit-1 positive (6% of the adenomas negative for ACTH, prolactin, growth hormone, TSH, and SF-1); the remaining 68 were potentially null cell adenomas. Two of the Pit-1-positive adenomas displayed a paranuclear CAM 5.2 staining pattern suggestive of a sparsely granulated somatotroph adenoma; however, only one case contained fibrous bodies within a majority of the adenoma cells. Our data suggests that Pit-1 can be utilized as a second tier immunostain in cases of clinically non-functioning adenomas that are immunonegative for ACTH, prolactin, growth hormone, TSH, and SF-1 in order to further segregate rare cases of Pit-1 positive adenomas from null cell adenomas. Pit-1 immunostaining can recognize rare cases of sparsely granulated somatotroph adenomas that appear immunonegative for growth hormone, as well as rare cases of other Pit-1-positive adenomas that are negative for Pit-1 lineage hormones. Overall, pituitary adenomas of the Pit-1 lineage that do not produce prolactin, growth hormone, or TSH are rare, with only four cases identified in the current study. PMID- 28994037 TI - Pathophysiology, diagnosis and treatment of inherited distal renal tubular acidosis. AB - Distal renal tubular acidosis (dRTA) is a tubular disorder with a primary defect of urinary acidification and acid excretion in the collecting duct system. Consequently, patients develop hyperchloremic metabolic acidosis with an inappropriately alkaline urine. Inherited forms of dRTA are due to mutations in at least three distinct genes: SLC4A1, ATP6V1B1, ATP6V0A4. Mutations in SLC4A1 (AE1) are inherited either in an autosomal dominant manner or in a recessive one. ATP6V1B and ATP6V0A4 mutations affect two different subunits of the vacuolar H+ ATPase proton-pump, the B1 and a4 subunits, and are inherited in an autosomal recessive manner. Clinical manifestations of inherited forms of dRTA usually occur during infancy or childhood. However, heterozygous carriers of ATP6V1B1 and ATP6V0A4 mutations may have a higher risk of developing nephrolithiasis and nephrocalcinosis in adulthood, respectively. In full forms of dRTA, patients may present with mild clinical symptoms, such as mild metabolic acidosis and incidental detection of kidney stones, as well as with more severe manifestations such as failure to thrive, severe metabolic acidosis, and nephrocalcinosis. Progressive sensorineural hearing loss develops in the majority of patients with recessive dRTA (ATP6V1B1 and ATP6V0A4 mutations). Some patients with recessive dRTA may also develop abnormal widening of the vestibular aqueduct. This review will discuss our current understanding of the pathophysiology of inherited forms of dRTA, diagnosis and prognosis of patients, and therapy. PMID- 28994040 TI - The Protective Effect of Selenium on the Chicken Pancreas against Cadmium Toxicity via Alleviating Oxidative Stress and Autophagy. AB - Cadmium (Cd) is a highly toxic heavy metal that can affect human and animal health. Selenium (Se) is an essential microelement that can protect various organs against toxic heavy metals. Although many studies have investigated the adverse effect of Cd in rats and several other animals, little is known regarding the mechanisms of Cd-induced autophagy in the chicken pancreas and the antagonistic effect of Se on Cd. In the current study, we fed chickens Se, Cd, or Se and Cd supplements to establish the Se and Cd interaction model and to measure the concentrations of Se and Cd in the chicken pancreas. The ultrastructure changes of the chicken pancreas were also observed, and we detected oxidative stress indexes in each group. The expression levels of autophagy-related genes were also examined. We found that Cd exposure could increase the concentration of Cd, the activities of total superoxide dismutase (T-SOD), catalase (CAT), and glutathione peroxidase (GSH-Px); and the total antioxidant capacity (T-AOC) content in the chicken pancreas. The protein expression levels of dynein, Beclin1, LC3-1, LC3-2, and Atg5 were increased and that of TOR was decreased under Cd exposure conditions. However, the changes induced by Cd were significantly alleviated by Se. This study suggested that Cd could accumulate in the chicken pancreas and lead to oxidative stress and autophagy. Se was shown to antagonize Cd toxicity though reducing Cd accumulation, alleviating oxidative stress, and inhibiting autophagy. This study revealed a concrete mechanism for the Se antagonism of Cd and might provide a new clue for the detoxification of Cd poisoning. PMID- 28994038 TI - Clusia hilariana and Eugenia uniflora as bioindicators of atmospheric pollutants emitted by an iron pelletizing factory in Brazil. AB - The objectives of this work were to evaluate if the pollution emitted by the pelletizing factory causes visual symptoms and/or anatomical changes in exposed Eugenia uniflora and Clusia hilariana, in active biomonitoring, at different distances from a pelletizing factory. We characterize the symptomatology, anatomical, and histochemistry alterations induced in the two species. There was no difference in the symptomatology in relation to the different distances of the emitting source. The foliar symptoms found in C. hilariana were chlorosis, necrosis, and foliar abscission and, in E. uniflora, were observed necrosis punctuais, purple spots in the leaves, and increase in the emission of new leaves completely purplish. The two species presented formation of a cicatrization tissue. E. uniflora presented reduction in the thickness of leaf. In C. hilariana, it was visualized hyperplasia of the cells and the adaxial epidermis did not appear collapsed due to thick cuticle and cuticular flanges. Leaves of C. hilariana showed positive staining for iron, protein, starch, and phenolic compounds. E. uniflora showed positive staining for total phenolic compounds and starch. Micromorphologically, there was accumulation of particulate matter on the leaf surface, obstruction of the stomata, and scaling of the epicuticular wax in both species. It was concluded that the visual and anatomical symptoms were efficient in the diagnosis of the stress factor. C. hilariana and E. uniflora showed to be good bioindicators of the atmospheric pollutants emitted by the pelletizing factory. PMID- 28994042 TI - ? PMID- 28994043 TI - ? PMID- 28994041 TI - Quantification of Wilms' tumor 1 mRNA by digital polymerase chain reaction. AB - Wilms' tumor 1 (WT1) is overexpressed in various hematopoietic tumors and widely used as a marker of minimal residual disease. WT1 mRNA has been analyzed using quantitative real-time polymerase chain reaction (real-time PCR). In the present study, we analyzed 40 peripheral blood and bone marrow samples obtained from cases of acute myeloid leukemia, acute lymphoblastic leukemia, and myelodysplastic syndrome at Sapporo Medical University Hospital from April 2012 to January 2015. We performed quantification of WT1 was performed using QuantStudio 3D Digital PCR System (Thermo Fisher Scientific) and compared the results between digital PCR and real-time PCR technology. The correlation between digital PCR and real-time PCR was very strong (R = 0.99), and the detection limits of the two methods were equivalent. Digital PCR was able to accurately detect lower WT levels compared with real-time PCR. Digital PCR technology can thus be utilized to predict WT1/ABL1 expression level accurately and should thus be useful for diagnosis or the evaluation of drug efficiency in patients with leukemia. PMID- 28994044 TI - ? PMID- 28994045 TI - ? PMID- 28994046 TI - ? PMID- 28994047 TI - ? PMID- 28994048 TI - ? PMID- 28994050 TI - ? PMID- 28994049 TI - ? PMID- 28994051 TI - ? PMID- 28994052 TI - ? PMID- 28994054 TI - ? PMID- 28994055 TI - ? PMID- 28994057 TI - ? PMID- 28994056 TI - ? PMID- 28994058 TI - ? PMID- 28994060 TI - ? PMID- 28994059 TI - ? PMID- 28994061 TI - ? PMID- 28994062 TI - ? PMID- 28994063 TI - ? PMID- 28994064 TI - ? PMID- 28994066 TI - ? PMID- 28994065 TI - [How can prevention be made successful?] PMID- 28994067 TI - ? PMID- 28994068 TI - [Flu vaccination - Protect also pregnant women and your team!] PMID- 28994069 TI - ? PMID- 28994070 TI - ? PMID- 28994071 TI - ? PMID- 28994072 TI - ? PMID- 28994074 TI - ? PMID- 28994073 TI - ? PMID- 28994075 TI - ? PMID- 28994077 TI - ? PMID- 28994076 TI - ? PMID- 28994079 TI - ? PMID- 28994078 TI - ? PMID- 28994081 TI - ? PMID- 28994080 TI - ? PMID- 28994082 TI - ? PMID- 28994083 TI - ? PMID- 28994084 TI - ? PMID- 28994085 TI - ? PMID- 28994086 TI - ? PMID- 28994088 TI - ? PMID- 28994087 TI - ? PMID- 28994089 TI - ? PMID- 28994090 TI - ? PMID- 28994091 TI - ? PMID- 28994092 TI - ? PMID- 28994093 TI - Circulating tumor cells in urological cancers. AB - Circulating tumor cells (CTC) represent a very small subpopulation of the cancer cells found in the bloodstream of patients in the metastatic phase of neoplastic disease. Due to the timeline of the disease, they are regarded as a negative prognostic marker. This study focused on determining CTC percentages; these values vary be-tween different types of cancer. In addition to their diagnostic use, CTCs may also be used to treat the disease. Calculating CTC population size and analyzing their biology in patients in advanced stages of cancer may prove valuable in creating a molecular profile for the disease. This would strongly encourage diagnostics and enable personalized treatment. We here present an analysis of recent data on CTCs in urological cancers and their potential uses. PMID- 28994094 TI - Novel prognostic molecular factors: a quantum leap in the field of chronic lymphocytic leukemia. AB - Cytogenetic lesions do not completely explain clinical heterogeneity of chronic lymphocytic leukemia (CLL). The 2016 revision of the World Health Organization classification 2008 indicated that molecular lesions of TP53, NOTCH1, SF3B1 and BIRC3 have potential clinical relevance and could be integrated into an updated risk profile. The negative clinical implications of TP53 disruptions are well constituted and patients with these mutations should be considered for novel, small molecule signal transduction inhibitors therapies. Mutations of NOTCH1, SF3B1 and BIRC3 are associated with poor prognosis. Patients with mutated SF3B1 or NOTCH1 genes present shorter time to first treatment compared to unmutated group. NOTCH1 mutations are related to a high risk of Richter's syndrome transformation, especially in case of TP53 disruptions' coexistence. Large studies on MYD88 mutations in CLL have not explained clearly their clinical importance.The aim of this paper is to provide a comprehensive review on novel molecular aberrations identified in CLL. PMID- 28994095 TI - Repression of the Notch pathway prevents liver damage in streptozotocin-induced diabetic mice. AB - INTRODUCTION: Sunitinib is an oral inhibitor of vascular endothelial growth factor that is used to treat a variety of cancer. There are limited data regarding the effect of sunitinib on diabetes. In the liver, Notch signaling plays an important role in liver tissue development and homeostasis and its dysfunction is associated with liver pathol-ogies. The aim of the present study is to investigate the effects of sunitinib on streptozotocin (STZ)-induced diabetic liver in mice models. MATERIAL AND METHODS: An experimental diabetes mellitus (DM) model was created in 28 male CD-1 mice. Twenty-eight male CD-1 mice divided in four groups (n = 7 each) were used; control mice (C), control mice treated with sunitinib (C + S), diabetic mice (DM), and diabetic mice treated with sunitinib (DM + S) for four weeks. The histopathological changes in the liver were examined by histochemistry and immunohistochemistry. Immunoreactivity of Notch1, Jagged1, DLL-1 and VEGF were evaluated in control and diabetic mice after sunitinib treatment. RESULTS: The significant morphological changes in the liver were mostly seen in hepatocytes that were hyper-trophied in the DM mice, with an increased amount of eosinophilic granules; moreover, some hepatocytes contained empty vacuole-like structures. The livers of the DM mice revealed increased deposition of collagen fibers. After sunitinib treatment the hepatocytes and hepatic lobules had almost similar morphology to control mice. The immunoreactivities of Notch1, Jagged1, DLL-1 and VEGF in hepatocytes were significantly lower in the DM group when compared with the C, DM + S and C + S group treated with sunitinib. CONCLUSIONS: These results suggest that sunitinib effectively protects the liver from diabetes-induced damage through the inhibition of the Notch pathway. PMID- 28994096 TI - Impaired expression of testicular androgen receptor and collagen fibers in the testis of diabetic rats under HAART: the role of Hypoxis hemerocallidea. AB - INTRODUCTION: Wide spectrum of alterations associated with highly active antiretroviral therapy (HAART) has been reported. The current study aimed at evaluating the role of Hypoxis hemerocallidea (HH) aqueous extract on the testosterone levels, expression of androgen receptors and collagen fibers in the testes of streptozoto-cin-nicotinamide-induced diabetic rats under HAART regimen. MATERIAL AND METHODS: Sixty two adult male Sprague-Dawley rats (189.0 +/- 4.5 g) were divided into eight groups (8 animals in each treatment groups and 6 rats in the control group). Diabetes was induced by a single intraperi-toneal injection of nicotinamide (110 mg/kg bw) followed by streptozotocin (45 mg/kg bw) and the animals were then subjected to various treatments with HAART, HH extract or melatonin. At the end of the experiment, blood samples were collected to measure serum testosterone levels. Testes were fixed in buffered formaldehyde and paraffin processed. The expression of androgen receptor (AR) was assessed by immunohistochemistry and collagen fibers were visualized by Masson trichrome staining. RESULTS: Serum testosterone level was drastically (p < 0.0001) reduced in all rats with induced diabetes. In the testis of diabetic rats increased collagen fibers deposition with varying derangements in germinal epithelium of spermatogenic layers were observed. Intertubular hemorrhages and absence of spermatozoa were also noted in the testes of diabetic rats subjected to HAART. Reduced immunoexpression of ARs was found in the nuclei of Sertoli cells and the cytoplasm of spermatogonia and spermatocytes in III-IV stages of the seminiferous epithelium cycle of diabetic animals treated with different dosages of HH alone and those treated with HAART concomitantly with melatonin and HH. The expression of ARs was almost negative in the testes of rats treated with HAART alone. CONCLUSIONS: Concomitant treatment of rats with aqueous HH extract during the HAART did not change se-rum testosterone level nor mitigate the altered expression of collagen fibers and androgen receptor resulting from STZ nicotinamide-induced diabetes. Therefore, anti-diabetic properties of Hypoxis extract require further investigation. PMID- 28994097 TI - Reliability of histopathological examination and immunohistochemistry of a single biopsy for evaluation of endometrial health in Icelandic mares. AB - INTRODUCTION: Endometritis and endometrosis have been and still are the major reasons for infertility in mares. The diagnosis of endometritis can be based on cytology and microbiology, but endometrial biopsy is still the only way to diagnose endometrosis in the mare. Our study attempted to determine if a single biopsy using his-topathology and immunohistochemistry is sufficient to ascertain reasons for infertility in Icelandic mares. The objectives of this study were to examine the relationship between deviations in endometrial biopsies in terms of prostaglandin-endoperoxide synthase-2 (PTGS-2) and fibronectin expression and polymorphonuclear cells (PMNs) infiltration, as well as scoring degeneration in two endometrial biopsies. MATERIAL AND METHODS: Materials were collected from 53 Icelandic breed mares, from whom two endometrial biopsies were collected and they were used for histopathology and for immunohistochemistry for PTGS-2 and fibronectin. RESULTS: In our study, twenty-six of 53 mares (49%) showed differences in the biopsy score between the left and the right uterine horns (p = 0.002). There were statistically significant differences in fibronectin expression (p = 0.001), as well as in PTGS-2 expression in the superficial epithelium (p = 0.017). CONCLUSIONS: Significant differences in the biopsy score, and fibronectin and PTGS-2 expression, between two endometrial biopsies obtained from individual mares demonstrated that a single biopsy could be insufficient for diagnosing uterine health status in Icelandic mares. PMID- 28994098 TI - The impact of antiandrogen flutamide on the hypoxia inducible factor 1a and vascular endothelial growth factor A gene and protein expression in the pig placenta during late pregnancy. AB - INTRODUCTION: In contrast to estradiol action, little is known about androgen signaling in placental development. The purpose of this study was to evaluate the impact of diminished androgen action on hypoxia inducible factor 1a (HIF-1a) and vascular endothelial growth factor A (VEGFA) protein expression as well as their mRNAs in the structures of fetal and maternal parts of porcine placenta during late pregnancy. MATERIAL AND METHODS: Pregnant pigs were injected daily with antiandrogen flutamide, at a dose of 50 mg/kg body weight at different stages of pregnancy: between gestational days 83-89 (90 dpc) and 101-107 (108 dpc). Control groups (90 dpc or 108 dpc) were treated with vehicle (corn oil). One day after the last injection animals were sacrificed and tissues were collected. Tissue samples were frozen for mRNA isolation or fixed for immu-nohistochemistry (IHC). The expression of HIF-1a and VEGFA were investigated by real-time PCR and IHC. RESULTS: Flutamide treatment caused changes in both HIF-1a and VEGFA mRNA levels only in the placentas of the 90 dpc group. Relative optical density analysis showed decreased HIF-1a and increased VEGFA protein expression in the placentas obtained from flutamide-treated 108 dpc group while no differences were observed in the 90 dpc group. CONCLUSIONS: Experimentally induced androgen deficiency in pigs deregulates the expression of some genes important for placental blood circulation. We suggest that androgens are involved in the control of expression of HIF-1a and VEGFA in porcine placenta during late pregnancy. PMID- 28994099 TI - Sociodemographic factors modulate the spatial response of brown bears to vacancies created by hunting. AB - There is a growing recognition of the importance of indirect effects from hunting on wildlife populations, e.g. social and behavioural changes due to harvest, which occur after the initial offtake. Nonetheless, little is known about how the removal of members of a population influences the spatial configuration of the survivors. We studied how surviving brown bears (Ursus arctos) used former home ranges that had belonged to casualties of the annual bear hunting season in southcentral Sweden (2007-2015). We used resource selection functions to explore the effects of the casualty's and survivor's sex, age and their pairwise genetic relatedness, population density and hunting intensity on survivors' spatial responses to vacated home ranges. We tested the competitive release hypothesis, whereby survivors that increase their use of a killed bear's home range are presumed to have been released from intraspecific competition. We found strong support for this hypothesis, as survivors of the same sex as the casualty consistently increased their use of its vacant home range. Patterns were less pronounced or absent when the survivor and casualty were of opposite sex. Genetic relatedness between the survivor and the casualty emerged as the most important factor explaining increased use of vacated male home ranges by males, with a stronger response from survivors of lower relatedness. Relatedness was also important for females, but it did not influence use following removal; female survivors used home ranges of higher related female casualties more, both before and after death. Spatial responses by survivors were further influenced by bear age, population density and hunting intensity. We have shown that survivors exhibit a spatial response to vacated home ranges caused by hunting casualties, even in nonterritorial species such as the brown bear. This spatial reorganization can have unintended consequences for population dynamics and interfere with management goals. Altogether, our results underscore the need to better understand the short- and long-term indirect effects of hunting on animal social structure and their resulting distribution in space. PMID- 28994100 TI - Temporal changes in hamlet communities (Hypoplectrus spp., Serranidae) over 17 years. AB - Transect surveys of hamlet communities (Hypoplectrus spp., Serranidae) covering 14 000 m2 across 16 reefs off La Parguera, Puerto Rico, are presented and compared with a previous survey conducted in the year 2000. The hamlet community has noticeably changed over 17 years, with a > 30% increase in relative abundance of the yellowtail hamlet Hypoplectrus chlorurus on the inner reefs at the expense of the other hamlet species. The data also suggest that the density of H. chlorurus has declined and that its distribution has shifted towards shallower depths. Considering that H. chlorurus has been previously identified as one of the few fish showing a positive association with seawater turbidity on the inner reefs of La Parguera and that sedimentation of terrestrial origin has increased over recent decades on these reefs, it is proposed that turbidity may constitute an important but so far overlooked ecological driver of hamlet communities. PMID- 28994101 TI - When to choose dynamic vs. static social network analysis. AB - There is increasing interest in using dynamic social networks in the study of animal sociality and its consequences. However, there is a general lack of guidance on the when and how such an approach will be valuable. The aim of this paper is to provide a guide on when to choose dynamic vs. static social network analysis, and how to choose the appropriate temporal scale for the dynamic network. I first discuss the motivations for using dynamic animal social networks. I then provide guidance on how to choose between dynamic networks and the "standard" approach of using static networks. I discuss this in the context of the temporal scale of changes observed, of their predictability and of the data availability. Dynamic networks are important in a number of scenarios. First, if the network data are being compared to independent processes, such as the spread of information or disease or environmental changes, then dynamic networks will provide more accurate estimates of spreading rates. Second, if the network has predictable patterns of change, for example diel cycles or seasonal changes, then dynamic networks should be used to capture the impact of these changes. Third, dynamic networks are important for studies of spread through networks when the relationship between edge weight and transmission probability is nonlinear. Finally, dynamic social networks are also useful in situations where interactions among individuals are dense, such as in studies of captive groups. The use of static vs. dynamic network requires careful consideration, both from a research question perspective and from a data perspective, and this paper provides a guide on how to evaluate the relative importance of these. PMID- 28994102 TI - Site affinity of whitespotted eagle rays Aetobatus narinari assessed using photographic identification. AB - Photographic identification was used to track the movements of the whitespotted eagle ray Aetobatus narinari around South Caicos, Turks and Caicos Islands. A total of 165 individuals were identified, aided by the computer program I3 S Spot. The sex ratio across all study sites in 2015 was not significantly different from 1:1 (chi2 = 2.8, P > 0.05). 33.9% of all individual rays were resighted at least once and the maximum number of days between the first and last sighting was 1640 (median 165, interquartile range, IQR = 698). Sightings of individuals occurred at locations differing from the original sighting location 24.6% of the time (0.7-20 km away). The entire population around South Caicos has yet to be sampled and these rays exhibited site affinity during the study period; they are either resident to South Caicos or are using the area for parts of the year before making movements elsewhere and then returning. Given these results, A. narinari is suited to local-scale management and conservation efforts. PMID- 28994103 TI - Migratory animals feel the cost of getting sick: A meta-analysis across species. AB - Migratory animals are widely assumed to play an important role in the long distance dispersal of parasites, and are frequently implicated in the global spread of zoonotic pathogens such as avian influenzas in birds and Ebola viruses in bats. However, infection imposes physiological and behavioural constraints on hosts that may act to curtail parasite dispersal via changes to migratory timing ("migratory separation") and survival ("migratory culling"). There remains little consensus regarding the frequency and extent to which migratory separation and migratory culling may operate, despite a growing recognition of the importance of these mechanisms in regulating transmission dynamics in migratory animals. We quantitatively reviewed 85 observations extracted from 41 studies to examine how both infection status and infection intensity are related to changes in body stores, refuelling rates, movement capacity, phenology and survival in migratory hosts across taxa. Overall, host infection status was weakly associated with reduced body stores, delayed migration and lower survival, and more strongly associated with reduced movement. Infection intensity was not associated with changes to host body stores, but was associated with moderate negative effects on movement, phenology and survival. In conclusion, we found evidence for negative effects of infection on host phenology and survival, but the effects were relatively small. This may have implications for the extent to which migratory separation and migratory culling act to limit parasite dispersal in migratory systems. We propose a number of recommendations for future research that will further advance our understanding of how migratory separation and migratory culling may shape host-parasite dynamics along migratory routes globally. PMID- 28994104 TI - Epidemiology of keratinocyte carcinomas after organ transplantation. AB - Keratinocyte carcinoma (KC) is the most common type of cancer among white populations, but it is even more common among solid organ transplant recipients (OTRs). The most frequent histological type of KC among OTRs is cutaneous squamous cell carcinoma (cSCC), followed by basal cell carcinoma, although the reverse is seen in the general population. Metastatic cSCCs are more frequent, and mortality is increased compared with immunocompetent populations. There is strong evidence that the risk of KC among OTRs rises with increasing time after transplantation and older age at transplantation, and that KC is enhanced in those with sun-damaged skin. This evidence suggests that accelerated accumulation of genetic damage from several sources leads to excess KC in OTRs. We describe international variation in KC and focus on trends in immunosuppressive regimens, the role of ultraviolet susceptibility and exposure, and the contribution of genetics to tumour development. Further epidemiological studies are needed to address gaps in our understanding of the mediation of excess KC by immunosuppressive drugs, viral infection, genetic susceptibility, timing of relevant ultraviolet exposure or some combination of these factors. PMID- 28994105 TI - Surgical management of apocrine hidrocystoma on the penile shaft. PMID- 28994106 TI - Safety Culture and Mortality after Acute Myocardial Infarction: A Study of Medicare Beneficiaries at 171 Hospitals. AB - OBJECTIVES: To investigate the association between hospital safety culture and 30 day risk-adjusted mortality for Medicare patients with acute myocardial infarction (AMI) in a large, diverse hospital cohort. SUBJECTS: The final analytic cohort consisted of 19,357 Medicare AMI discharges (MedPAR data) linked to 257 AHRQ Hospital Survey on Patient Safety Culture surveys from 171 hospitals between 2008 and 2013. STUDY DESIGN: Observational, cross-sectional study using hierarchical logistic models to estimate the association between hospital safety scores and 30-day risk-adjusted patient mortality. Odds ratios of 30-day, all cause mortality, adjusting for patient covariates, hospital characteristics (size and teaching status), and several different types of safety culture scores (composite, average, and overall) were determined. PRINCIPAL FINDINGS: No significant association was found between any measure of hospital safety culture and adjusted AMI mortality. CONCLUSIONS: In a large cross-sectional study from a diverse hospital cohort, AHRQ safety culture scores were not associated with AMI mortality. Our study adds to a growing body of investigations that have failed to conclusively demonstrate a safety culture-outcome association in health care, at least with widely used national survey instruments. PMID- 28994107 TI - FAT1 modulates EMT and stemness genes expression in hypoxic glioblastoma. AB - Glioblastoma (GBM) is characterized by the presence of hypoxia, stemness and local invasiveness. We have earlier demonstrated that FAT1 promotes invasiveness, inflammation and upregulates HIF-1alpha expression and its signaling in hypoxic GBM. Here, we have identified the role of FAT1 in regulating EMT (epithelial mesenchymal transition) and stemness characteristics in GBM. The expression of FAT1, EMT (Snail/LOX/Vimentin/N-cad), stemness (SOX2/OCT4/Nestin/REST) and hypoxia markers (HIF-1alpha/VEGF/PGK1/CA9) was upregulated in >=39% of GBM tumors (n = 31) with significant positive correlation (p <= 0.05) of the expression of FAT1 with LOX/Vimentin/SOX2/HIF-1alpha/PGK1/VEGF/CA9. Furthermore, positive correlation (p <= 0.01) of FAT1 with Vimentin/N-cad/SOX2/REST/HIF-1alpha has been observed in TCGA GBM-dataset (n = 430). Analysis of cells (U87MG/A172) exposed to severe hypoxia (0.2%O2 ) revealed elevated mRNA expression of FAT1, EMT (Snail/LOX/Vimentin/N-cad), stemness (SOX2/OCT4/Nestin/REST) and hypoxia markers (HIF-1alpha/PGK1/VEGF/CA9) as compared to their normoxic (20%O2 ) counterparts. FAT1 knockdown in U87MG/A172 maintained in severe hypoxia and in normoxic primary glioma cultures led to significant reduction of EMT/stemness markers as compared to controls. HIF-1alpha knockdown in U87MG cells markedly reduced the expression of all the EMT/stemness markers studied except for Nestin and SOX2 which were more under the influence of FAT1. This indicates FAT1 has a novel regulatory effect on EMT/stemness markers both via or independent of HIF-1alpha. The functional relevance of our study was corroborated by significant reduction in the number of soft-agar colonies formed in hypoxic-siFAT1 treated U87MG cells. Hence, our study for the first time reveals FAT1 as a novel regulator of EMT/stemness in hypoxic GBM and suggests FAT1 as a potential therapeutic candidate. PMID- 28994108 TI - Value of a molecular screening program to support clinical trial enrollment in Asian cancer patients: The Integrated Molecular Analysis of Cancer (IMAC) Study. AB - The value of precision oncology initiatives in Asian contexts remains unresolved. Here, we review the institutional implementation of prospective molecular screening to facilitate accrual of patients into biomarker-driven clinical trials, and to explore the mutational landscape of advanced tumors occurring in a prospective cohort of Asian patients (n = 396) with diverse cancer types. Next generation sequencing (NGS) and routine clinicopathological assays, such as immunohistochemistry, copy number analysis and in situ hybridization tests, were performed on tumor samples. Actionable biomarker results were used to identify eligibility for early-phase, biomarker-driven clinical trials. Overall, NGS was successful in 365 of 396 patients (92%), achieving a mean depth of 1,943* and coverage uniformity of 96%. The median turnaround time from sample receipt to return of genomic results was 26.0 days (IQR, 19.0-39.0 days). Reportable mutations were found in 300 of 365 patients (82%). Ninety-one percent of patients at study enrollment indicated consent to receive incidental findings and willingness to undergo genetic counseling if required. The most commonly mutated oncogenes included KRAS (19%), PIK3CA (16%), EGFR (5%), BRAF (3%) and KIT (3%); while the most frequently mutated tumor suppressor genes included TP53 (40%), SMARCB1 (12%), APC (8%), PTEN (6%) and SMAD4 (5%). Among 23 patients enrolled in genotype-matched trials, median progression-free survival was 2.9 months (IQR, 1.5-4.0 months). Nine of 20 evaluable patients (45%; 95% CI, 23.1-68.5%) derived clinical benefit, including 3 partial responses and 6 with stable disease lasting >= 8 weeks. PMID- 28994109 TI - The Hospital: Still the Doctors' Workplace(s)-A Cautionary Note for Approaches to Safety and Value Improvement. PMID- 28994110 TI - Relapsing polychondritis, an underestimated dermatological urgency: case report and literature review. AB - BACKGROUND: Relapsing polychondritis is an autoimmune multisystemic disease with primary chondral involvement. Its high mortality and morbidity make it a real clinical challenge. CASE DESCRIPTION: A 32-year-old woman with a history of relapsing polychondritis, refractory to multiple treatments, with multisystem compromise, imminent risk of death due to severe tracheobronchial damage and difficult ventilatory support, and successful treatment with infliximab. DISCUSSION AND EVALUATION: Several treatments have been described in the literature, such as nonsteroidal anti-inflammatory drugs, corticosteroids, dapsone, azathioprine, cyclosporine, cyclophosphamide, and methotrexate. However, the cases refractory to conventional therapy may lead to chronicity, irreversibility, and death. As a result, a third-line therapy could improve the prognosis of these patients. CONCLUSIONS: Biological therapy is a good option for disease control and quality of life improvement. In addition, the physician should consider these treatments to avoid the chronicity and risk of death of these patients. PMID- 28994111 TI - Retrospective study of the effect of remifentanil use during labor on fetal heart rate patterns. AB - OBJECTIVE: To investigate possible associations between remifentanil and the appearance of sinusoidal heart rate patterns in fetuses, and neonatal outcomes. METHODS: The present retrospective cohort study included data from patients at over 37 weeks of singleton or multiple pregnancies attending Zuyderland Medical Center, Sittard, the Netherlands, in labor between June 1, and August 31, 2015. Patient data were stratified by whether remifentanil was administered during delivery (remifentanil group) or not (control group), and fetal heart rate tracings were reviewed to identify sinusoidal heart rate patterns. The neonatal outcomes compared were 5-minute Apgar scores and umbilical artery pH. RESULTS: There were 119 patients included in the study; 60 in the remifentanil group and 59 in the control group. Tracings from 20 (33%) patients in the remifentanil group exhibited a sinusoidal heart rate pattern after remifentanil administration, compared with 5 (8%) patients in the control group (P=0.001). The median time before the onset of sinusoidal patterns after remifentanil administration was 12 minutes. No adverse neonatal outcomes were recorded in either group. CONCLUSION: Remifentanil use during labor was associated with the occurrence of sinusoidal heart rate patterns in the fetus; this was not associated with adverse neonatal outcomes. PMID- 28994112 TI - Celastrol attenuates pain and cartilage damage via SDF-1/CXCR4 signalling pathway in osteoarthritis rats. AB - OBJECTIVES: Celastrol has attracted wide interests for its anticancer and anti inflammation properties, and studies have demonstrated that celastrol negatively modulates the stromal cell-derived factor-1 (SDF-1) and receptor C-X-C chemokine receptor type 4 (CXCR4) signalling. We aim in this study to investigate the effects of celastrol in osteoarthritis (OA) in vivo and explored the underlying molecular mechanisms. METHODS: We established a monoiodoacetate (MIA)-induced rat OA model and evaluated the joint pain and cartilage damage with or without celastrol treatments. We further assessed the alterations of the SDF-1/CXCR4 pathway and cartilage-specific genes, at both mRNA and protein levels. KEY FINDINGS: Celastrol significantly attenuated the joint pain and cartilage damage induced by MIA in OA rats and suppressed the upregulation of SDF-1/CXCR4 and associated genes caused by MIA injections. Furthermore, MIA induced a decrease in cartilage-specific genes which was also prevented by celastrol treatments. CONCLUSIONS: Celastrol ameliorate OA in vivo as evidenced by the attenuated joint pain and less cartilage damage in OA rats given celastrol treatments, an effect mediated via suppression of the SDF-1/CXCR4 pathway. PMID- 28994114 TI - Macrophage subtypes in recurrent nodular basal cell carcinoma after Mohs micrographic surgery. AB - BACKGROUND: The macrophages associated with solid tumors are related to the progression or regression of tumors, depending on the differentiation in M1 or M2. M2 subtype promotes angiogenesis, remodeling, and tissue repair (tumor proliferation). In contrast, M1 produces toxic mediators and presents antigens, destroying microorganisms and tumor cells. The microenvironment of most aggressive forms of basal cell carcinoma (BCC) shows an increase in macrophages due to M2 phenotype compared to noninvasive forms. The treatment of nodular BCC by Mohs micrographic surgery (MMS) provides high cure rates, but relapses can occur. AIMS: To compare the total population of macrophages and their subpopulations M1 and M2 in cases of recurrent and nonrecurrent nodular BCC after excision by MMS. MATERIALS & METHODS: Histological sections obtained from paraffin blocks of nine cases of recurrent nodular BCC after MMS and 18 cases of nonrecurrent nodular BCC operated by MMS were immunostained for iNOS, CD204, CD163, and CD68. The expression of these markers was analyzed by image analysis. RESULTS: No significant differences were found between the groups in relation to the average percentage of M1 cells, M2 cells, and total cells. DISCUSSION AND CONCLUSION: A relationship was not seen between tumor-associated macrophages (TAM) and tumor recurrence. PMID- 28994115 TI - The effect of fertility treatment on adverse perinatal outcomes in women aged at least 40 years. AB - OBJECTIVE: To compare perinatal outcomes between spontaneous conception and assisted reproductive technologies (ART) among patients of advanced maternal age. METHODS: The present retrospective study included data from singleton pregnancies of women aged at least 40 years who delivered between January 1, 1991, and December 31, 2013, at Soroka University Medical Center, Beer Sheva, Israel. Demographic, obstetric, and perinatal data were compared between pregnancies conceived with ART (in vitro fertilization [IVF] or ovulation induction) and those conceived spontaneously. Multiple regression models were used to define independent predictors of adverse outcomes. RESULTS: A total of 8244 singleton pregnancies were included; 229 (2.8%) following IVF, 86 (1.0%) following ovulation induction, and 7929 (96.2%) were spontaneous. Preterm delivery (P<0.001), fetal growth restriction (FGR) (P<0.001), and cesarean delivery (P<0.001) demonstrated linear associations with the conception mode; the highest rates for each were observed for IVF, with decreased rates for ovulation induction and spontaneous conception. The incidence of gestational diabetes and hypertensive disorders were highest among pregnancies following ART. No association was observed between conception mode and perinatal mortality. Multivariate logistic regression demonstrated that IVF was independently associated with increased odds of preterm delivery (P<0.001) and FGR (P=0.027) compared with spontaneous conception. CONCLUSIONS: Among patients of advanced maternal age, ART were independently associated with increased FGR and preterm delivery rates compared with spontaneous pregnancies; perinatal mortality was comparable. PMID- 28994113 TI - Rates and predictors of success and failure in repeat epilepsy surgery: A meta analysis and systematic review. AB - OBJECTIVE: Medically refractory epilepsy is a debilitating disorder that is particularly challenging to treat in patients who have already failed a surgical resection. Evidence regarding outcomes of further epilepsy surgery is limited to small case series and reviews. Therefore, our group performed the first quantitative meta-analysis of the literature from the past 30 years to assess for rates and predictors of successful reoperations. METHODS: A PubMed search was conducted for studies reporting outcomes of repeat epilepsy surgery. Studies were excluded if they reported fewer than five eligible patients or had average follow ups < 1 year, and patients were excluded from analysis if they received a nonresective intervention. Outcomes were stratified by each variable of interest, and quantitative meta-analysis was performed to generate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Seven hundred eighty-two patients who received repeat resective epilepsy surgery from 36 studies were included. Engel I outcome was observed in 47% (n = 369) of patients. Significant predictors of seizure freedom included congruent over noncongruent electrophysiology data (OR = 3.6, 95% CI = 1.6-8.2), lesional over nonlesional epilepsy (OR = 3.2, 95% CI = 1.9-5.3), and surgical limitations over disease-related factors associated with failure of the first surgery (OR = 2.6, 95% CI = 1.3-5.3). Among patients with at least one of these predictors, seizure freedom was achieved in 58%. Conversely, the use of invasive monitoring was associated with worse outcome (OR = 0.4, 95% CI = 0.2-0.9). Temporal lobe over extratemporal/multilobe resection (OR = 1.5, 95% CI = 0.8-3.0) and abnormal over normal preoperative magnetic resonance imaging (OR = 1.9, 95% CI = 0.6-5.4) showed nonsignificant trends toward seizure freedom. SIGNIFICANCE: This analysis supports considering further resection in patients with intractable epilepsy who continue to have debilitating seizures after an initial surgery, especially in the context of factors predictive of a favorable outcome. PMID- 28994116 TI - Response to 'Effects of diesel exhaust particles on coagulation'. PMID- 28994117 TI - Melatonin ameliorates Abeta1-42 -induced Alzheimer's cognitive deficits in mouse model. AB - OBJECTIVES: The objective of this study was to evaluate whether melatonin could ameliorate cognitive function in Abeta1-42 -induced mouse model and its underlying mechanisms. METHODS: Series behaviour tests were performed to demonstrate the amelioration of cognitive function of the Alzheimer's disease (AD) mice induced by Abeta1-42 . Additionally, enzyme-linked immunosorbent assay was applied to detect the expression of Abeta1-42 , BACE1 and p-tau protein in the brain of the AD mice. JC-1 was performed to investigate the role in alleviating mitochondrial damage by melatonin in vitro. Western blot was used to detect the expression of melatonin on apoptosis-related factors caspase-3 and Bcl 2, as well as the expressions of GSK-3beta and PP2A to further determine the mechanisms of melatonin on the expression of p-tau protein. KEY FINDINGS: Melatonin significantly ameliorated the cognitive function and mitochondrial damage in AD mice, reduced the expression levels of GSK-3beta, caspase-3, Abeta1 42 , BACE1, p-tau protein and increased the expressions of PP2A and Bcl-2. CONCLUSION: From the overall results, we concluded that melatonin alleviated the mitochondrial damage effectively and decreased the expressions of the p-tau and some key proteins of apoptosis, leading to the improvement of cognitive function of the mice induced by Abeta1-42 . PMID- 28994119 TI - Naturally occurring omega-Hydroxyacids. AB - omega-Hydroxyacids are fatty acids bearing a hydroxyl group on the terminal carbon. They are found in mammals and higher plants and are often involved in providing a permeability barrier, the primary purpose of which is to reduce water loss. Some omega-hydroxyacid derivatives may be involved in waterproofing and signalling. The purpose of this review was to survey the known natural sources of omega-hydroxyacids. omega-Hydroxyacids are produced by two different P450 dependent mechanisms. The longer (30-34 carbons) omega-hydroxyacids are produced by chain extension from palmitic acid until the chain extends across the membrane in which the extension is taking place, and then the terminal carbon is hydroxylated. Shorter fatty acids can be hydroxylated directly to produce C16 and C18 omega-hydroxyacids found in plants and 20-eicosatetraenoic acid (20-HETE) by a different P450. The C16 and C18 omega-hydroxyacids are components of polymers in plants. The long-chain omega-hydroxyacids are found in epidermal sphingolipids, in giant-ring lactones from the sebum of members of the equidae, as a component of meibum and in carnauba wax and wool wax. PMID- 28994118 TI - Baccharis dracunculifolia DC (Asteraceae) selectively modulates the effector functions of human neutrophils. AB - OBJECTIVES: To examine whether the hydroalcoholic extract from Baccharis dracunculifolia leaves (BdE) modulates the human neutrophil oxidative metabolism, degranulation, phagocytosis and microbial killing capacity. METHODS: In-vitro assays based on chemiluminescence, spectrophotometry, flow cytometry and polarimetry were used, as well as docking calculations. KEY FINDINGS: At concentrations that effectively suppressed the neutrophil oxidative metabolism elicited by soluble and particulate stimuli (<10 MUg/ml), without clear signs of cytotoxicity, BdE (1) inhibited NADPH oxidase and myeloperoxidase activity; (2) scavenged H2 O2 and HOCl; (3) weakly inhibited phagocytosis; and (4) did not affect neutrophil degranulation and microbial killing capacity, the expression levels of TLR2, TLR4, FcgammaRIIa, FcgammaRIIIb and CR3 and the activity of elastase and lysozyme. Caffeic acid, one of the major B. dracunculifolia secondary metabolites, did not inhibit phagocytosis but interfered in the myeloperoxidase-H2 O2 -HOCl system by scavenging H2 O2 and HOCl, and interacting with the catalytic residues His-95, Arg-239 and Gln-91. CONCLUSIONS: BdE selectively modulates the effector functions of human neutrophils, inhibits the activity of key enzymes and scavenges physiological oxidant species. Caffeic acid contributes to lower the levels of oxidant species. Our findings help to unravel the mechanisms by which these natural products exert immunomodulatory action towards neutrophils. PMID- 28994121 TI - Navigating the new, transplanted self: how recipients manage the cognitive risks of organ transplantation. AB - The physiological risks of organ transplantation are well documented, but more poorly understood are the sociological ways in which organ recipients redefine themselves in reaction to physiological risks and social changes accompanying transplantation. This article analyses transplantation as a procedure that is not only physiologically risky but also poses risk to the social identity of the recipient, and explores how transplant recipients cognitively navigate transplantation surgery from waiting for to recovering after a transplant. It builds on previous sociological exploration of risk as a socially constructed process mediating experiences of health and illness with a focused contribution on explaining how individuals navigate risks posed to their social identities by major biophysical transformations. This article pointedly analyses narratives of fourteen organ recipients and the four dominant phases of identity management that emerged to create what we have coined as the new 'transplanted self', indicating the varied ways the individual social self emerges in response to the social risks of transplantation. We conclude that a better understanding of the recipient experience will contribute to improved care in the transplantation field. PMID- 28994120 TI - Complications After Endoscopic Laryngopharyngeal Surgery. AB - OBJECTIVES/HYPOTHESIS: Endoscopic laryngopharyngeal surgery (ELPS), a hybrid of head and neck surgery and gastrointestinal endoscopic treatment, has been attracting attention as a new therapeutic modality for superficial laryngopharyngeal cancers. Although this technique is less invasive than traditional open procedures, some complications including postoperative bleeding, subcutaneous emphysema, or aspiration pneumonia can occur after treatment. The purpose of this study was to investigate the complications associated with ELPS to better understand the indications for this procedure. STUDY DESIGN: Retrospective medical chart review. METHODS: One hundred five patients with 159 laryngeal or pharyngeal lesions were treated with ELPS between August 2009 and September 2015 at Kyoto University Hospital. In total, 147 resections were performed, and complications after the resections were reviewed. RESULTS: Of the 147 resections, postoperative bleeding, subcutaneous emphysema, and aspiration pneumonia were observed in 10, 17, and 10 cases, respectively. All cases with postoperative bleeding and aspiration pneumonia occurred in patients over 65 years of age. A history of taking anticoagulation/platelet medications, and macroscopic 0-IIa lesions were shown to correlate with postoperative bleeding after ELPS. Resection of lesions in the pyriform sinus was found to be associated with subcutaneous emphysema. CONCLUSIONS: All complications after ELPS were safely managed. A history of taking anticoagulation/platelet medications and macroscopic 0-IIa lesions were identified as risk factors for postoperative bleeding, whereas resection of pyriform sinus lesions was found to be a risk factor for subcutaneous emphysema. These risk factors should be carefully considered when treating pharyngeal and laryngeal lesions by ELPS. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:1546-1550, 2018. PMID- 28994124 TI - Disclosing hidden information in the electroencephalogram using advanced signal analytical techniques. PMID- 28994123 TI - Systematic review with meta-analysis: rifaximin for the prophylaxis of spontaneous bacterial peritonitis. AB - BACKGROUND: The primary and secondary prevention of spontaneous bacterial peritonitis (SBP) is recommended in high-risk patients with cirrhosis. Several studies evaluating the efficacy of rifaximin for SBP prophylaxis have yielded conflicting results. Rifaximin has the potential advantage of preventing bacterial overgrowth and translocation without the systemic side effects of broad spectrum antibiotics. AIM: To evaluate the efficacy of rifaximin in the primary and secondary prevention of SBP. METHODS: A literature search using five databases was performed to identify studies on the association between rifaximin and SBP. We performed two meta-analyses: (1) rifaximin compared to systemic antibiotics and (2) rifaximin compared to no antibiotics. Random-effect modelling was conducted to determine overall pooled estimates and 95% confidence intervals (CIs). RESULTS: Five studies with 555 patients (295 rifaximin, 260 systemic antibiotics) compared rifaximin with systemic antibiotics. The pooled odds ratio (OR) for SBP was 0.45 (95% CI 0.16-1.27; P = .13) in patients receiving rifaximin and strengthened on sensitivity analysis (OR 0.38, 95% CI 0.19-0.76, P = .01). In the analysis comparing rifaximin with no antibiotics, there were five studies with 784 patients (186 rifaximin, 598 no antibiotics). The OR for SBP was 0.34 (95% CI 0.11-0.99; P < .05) in patients receiving rifaximin. In subgroup analysis, rifaximin reduced the risk of SBP by 47% compared to no antibiotics for primary prophylaxis and by 74% compared to systemic antibiotics for secondary prophylaxis. CONCLUSION: Rifaximin may be effective in preventing SBP in patients with cirrhosis and ascites compared to systemically absorbed antibiotics and compared to placebo. PMID- 28994122 TI - Beta-blockers in hospitalised patients with cirrhosis and ascites: mortality and factors determining discontinuation and reinitiation. AB - BACKGROUND: It has been suggested that beta-blockers may increase mortality in patients with cirrhosis and refractory ascites but the effect of beta-blockers discontinuation or reinitiation has not been examined. AIMS: To compare, in hospitalised patients with cirrhosis and ascites, the effect of BB on survival and to examine the effect/predictors of beta-blockers discontinuation and reinitiation. METHODS: Sub-analysis of NACSELD (North American consortium for the study of end-stage liver disease, database containing prospective data on hospitalised patients with cirrhosis) data from 7 centres enrolling >100 patients with ascites. Data on BB discontinuation and reinitiation were collected by chart review. RESULTS: Seven hundred and sixteen patients, 307 (43%) on beta-blockers at admission and 366 (51%) with refractory ascites, were followed to death or hospital discharge. Beta-blocker use was associated with a lower white blood cell count at admission. Beta-blocker use in hospitalised patients with ascites was not associated with a higher mortality, even in those with refractory ascites. No significant changes in mean arterial pressure (MAP) were observed between groups. Discontinuation of beta-blockers (49%) was driven by low MAP, infection and acute kidney injury at time of discontinuation but was not associated with a higher mortality. Beta-blocker reinitiation occurred in 40% prior to discharge and was mainly driven by an increase in MAP. CONCLUSIONS: Beta-blocker use is safe in patients with cirrhosis and ascites (including those with refractory ascites) provided beta-blockers are discontinued in the presence of a low MAP and reinitiated once MAP reincreases. A potentially beneficial anti-inflammatory effect of beta-blockers is suggested. PMID- 28994125 TI - Propionibacterium acnes as an emerging pathogen in skull base osteomyelitis: A case series. AB - Skull base osteomyelitis (SBO) is recognized as a potentially life-threatening infection that has been classically attributed to Pseudomonas aeruginosa. However, growing data shows that the bacteriology of SBO is changing. Traditionally thought of as commensal bacterium, P. acnes has been implicated as a serious pathogen in other specialties. Building on a previous case report from our institution, we have identified three patients with SBO who are culture positive for Propionibacterium acnes as a single isolate. Herein, we describe the clinical history of the three patients, along with treatment, present outcome, and review of the literature. Laryngoscope, 128:332-335, 2018. PMID- 28994126 TI - Staphylococcus Aureus V8 protease disrupts the integrity of the airway epithelial barrier and impairs IL-6 production in vitro. AB - OBJECTIVE: Staphylococcus aureus (S. aureus) infection is known to contribute to the severity and recalcitrance of chronic rhinosinusitis (CRS), and its secreted products have been shown to alter the airway barrier. Extracellular proteases secreted by S. aureus are thought to be important in epithelial infection and immune evasion; however, their effect on airway mucosal barrier function is not known. METHODS: To investigate the impact of extracellular proteases on airway epithelial integrity, the purified S. aureus proteases V8 protease, Staphopain A, Staphopain B, Exfoliative toxin A, and serine protease-like A-F were applied to human nasal epithelial cell air-liquid interface (HNEC-ALI) cultures. Transepithelial electrical resistance (TEER), permeability (Papp) measurements, and immuno-localization of the tight junction proteins claudin-1 and ZO-1 were used to assess barrier integrity. Effects of the proteases on inflammation and cell viability were measured using interleukin-6 (IL-6) ELISA and a lactate dehydrogenase assay. RESULTS: Application of V8 protease to HNEC-ALI cultures caused a significant concentration and time-dependent decrease in TEER (22.67%, P < 0.0001), a reciprocal Papp increase (20.14-fold, P < 0.05), and a discontinuous ZO-1 immuno-localization compared to control. IL-6 production was significantly reduced in V8 protease-treated cells (153.5 pg/mL, P = 0.0069) compared to control (548.3 pg/mL), whereas no difference in cell viability was observed. CONCLUSION: S. aureus V8 protease causes dysfunction of mucosal barrier structure and function indicative of a leaky barrier. A reduction in IL-6 levels suggests that the mucosal immunity is impaired by this protease and thus has the potential to contribute to CRS recalcitrance. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:E8 E15, 2018. PMID- 28994127 TI - The negative impact of HBV/HCV coinfection on cirrhosis and its consequences. AB - BACKGROUND: Hepatitis B virus (HBV)/hepatitis C virus (HCV) confection has been rarely studied in nonasian series. AIM: To compare the characteristics of HBV/HCV coinfected patients to those of HBV- or HCV-monoinfected patients in the ANRS CO22 HEPATHER cohort study. PATIENTS AND METHODS: Of the 20 936 included patients, 95 had HBV/HCV coinfection (hepatitis B surface antigen, anti-HCV antibody and HCV RNA positive) and were matched with 375 HBV- and 380 HCV monoinfected patients on age, gender and time since HBV or HCV diagnosis. RESULTS: F3-F4 fibrosis was more frequent in coinfected patients (58%) than in HBV- (32%, P < .0001), but similar in HCV-monoinfected patients (52%, P = .3142). Decompensated cirrhosis was more frequent in coinfected patients (11%) than in HBV- (2%, P = .0002) or HCV- (4%, P = .0275) monoinfected patients. Past excessive alcohol use was more frequent in coinfected patients (26%) than in HBV (12%, P = .0011), but similar in HCV monoinfected patients (32%, P = .2868). Coinfected patients had a higher proportion with arterial hypertension (42%) than HBV- (26%) or HCV-monoinfected patients (25%) (P < .003). Multivariable analysis confirmed the association between F3-F4 fibrosis and HCV infection in HBV infected patients (OR = 3.84, 95% CI 1.99-7.43) and the association between decompensated cirrhosis and coinfection in HBV infected (OR = 5.58, 95% CI 1.42 22.0) or HCV infected patients (OR = 3.02, 95% CI 1.22-7.44). CONCLUSIONS: HCV coinfection harmfully affects liver fibrosis in HBV patients, while decompensated cirrhosis is increased in coinfected patients compared with HBV- or HCV monoinfected patients. HCV treatment is as safe and effective in coinfected as monoinfected patients and should be considered following the same rules as HCV monoinfected patients. PMID- 28994128 TI - Validity of automated measurement of left ventricular ejection fraction and volume using the Philips EPIQ system. AB - PURPOSE: To assess the efficiency and reproducibility of automated measurements of left ventricular (LV) volumes and LV ejection fraction (LVEF) in comparison to manually traced biplane Simpson's method. METHOD: This is a single-center prospective study. Apical four- and two-chamber views were acquired in patients in sinus rhythm. Two operators independently measured LV volumes and LVEF using biplane Simpson's method. In addition, the image analysis software a2DQ on the Philips EPIQ system was applied to automatically assess the LV volumes and LVEF. Time spent on each analysis, using both methods, was documented. Concordance of echocardiographic measures was evaluated using intraclass correlation (ICC) and Bland-Altman analysis. RESULTS: Manual tracing and automated measurement of LV volumes and LVEF were performed in 184 patients with a mean age of 67.3 +/- 17.3 years and BMI 28.0 +/- 6.8 kg/m2 . ICC and Bland-Altman analysis showed good agreements between manual and automated methods measuring LVEF, end-systolic, and end-diastolic volumes. The average analysis time was significantly less using the automated method than manual tracing (116 vs 217 seconds/patient, P < .0001). CONCLUSION: Automated measurement using the novel image analysis software a2DQ on the Philips EPIQ system produced accurate, efficient, and reproducible assessment of LV volumes and LVEF compared with manual measurement. PMID- 28994129 TI - Self-reported minor infections in patients with hidradenitis suppurativa and healthy controls. AB - BACKGROUND: Patients with hidradenitis suppurativa (HS) often report opportunistic infections such as herpes and urinary tract infections. AIM: To compare opportunistic infections in patients with HS against a group of healthy controls (HCs). METHODS: In total, 99 patients with HS and 109 HCs were recruited at random to this retrospective case-control study. We devised a questionnaire to explore the frequency of minor infections, general practitioner (GP) visits and sick days experienced during the past 6 months. Additionally, participants were asked if they felt unwell more often compared with their peers. RESULTS: Patients with HS felt unwell more often than did HCs (26.3% vs. 7.3%, P < 0.001). Although there was no difference between the groups in five of the seven diseases studied, patients with HS had a higher frequency of the common cold (P < 0.01) and genital herpes (P < 0.01). Number of pack-years of smoking did not affect risk of infections (Pearson correlation, P = 0.51). Subgroup analysis of nonsmokers found the same differences in frequency of minor infections, common cold and genital herpes between patients with HS and controls. CONCLUSIONS: Patients with HS appear to experience more frequently symptoms compatible with minor infections in general, and the common cold and genital herpes specifically. This results in more GP visits and more sick days. Further research is needed to determine if this is caused by an immunological hyper-reactive state in these patients or a reduced threshold for minor infections. PMID- 28994130 TI - Eruptive melanocytic naevi secondary to azathioprine: case report and review of the literature. PMID- 28994131 TI - Systematic review and meta-analysis: assessment of factors affecting disability in inflammatory bowel disease and the reliability of the inflammatory bowel disease disability index. AB - BACKGROUND: The Inflammatory Bowel Disease Disability Index (IBD-DI) has recently been developed for patients with Crohn's disease (CD) and ulcerative colitis (UC). AIM: To assess the severity of disability and associated factors using the IBD-DI, and review the validity of the IBD-DI as a tool. METHOD: Systematic review of cross-sectional studies. Patients included had UC or CD and were classified as active, in remission, or needing surgery, biological and/or steroid treatment. We included studies assessing disability using the IBD-DI and that were captured by electronic and manual searches (January 2017). The possibility of bias was evaluated with the Newcastle-Ottawa Scale. RESULTS: Nine studies were included with 3167 patients. Comparatively, patients with active disease had higher disability rates than those in remission (SMD [CI95] = 1.49[1.11, 1.88], I2 = 94%, P<.01), while patients on biological treatment had lower disability rates than those receiving corticosteroid treatment (SMD [CI95] = -0.22[-0.36, 0.08], I2 = 0%, P<.01). Disease activity and unemployment were found to be associated factors. The IBD-DI scored "good" for internal consistency, "fair" to "excellent" for intra-rater reliability and "excellent" for inter-rater reliability. Construct validity was "moderately strong" to "very strong" and structural validity was found to be mainly unidimensional. The IBD-DI had excellent responsiveness, while its interpretability was only useful on a group level. CONCLUSIONS: This systematic review and meta-analysis found a significant association between disease activity, treatment received and disability; although significant heterogeneity was found. The IBD-DI is reliable and valid, but further studies are needed to measure its interpretability. PMID- 28994132 TI - Fast and accurate multi-channel B1+ mapping based on the TIAMO technique for 7T UHF body MRI. AB - PURPOSE: Current methods for mitigation of transmit field B1+ inhomogeneities at ultrahigh field (UHF) MRI by multi-channel radiofrequency (RF) shimming rely on accurate B1+ mapping. This can be time consuming when many RF channels have to be mapped for in vivo body MRI, where the B1 maps should ideally be acquired within a single breath-hold. Therefore, a new B1+ mapping technique (B1TIAMO) is proposed. METHODS: The performance of this technique is validated against an established method (DREAM) in phantom measurements for a cylindrical head phantom with an 8-channel transmit/receive (Tx/Rx) array. Furthermore, measurements for a 32-channel Tx/Rx remote array are conducted in a large body phantom and the |B1+| map reliability is validated against simulations of the transmit RF field distribution. Finally, in vivo results of this new mapping technique for human abdomen are presented. RESULTS: For the head phantom (8-channel Tx/Rx coil), the single |B1+| comparison between B1 TIAMO, the direct DREAM measurements, and simulation data showed good agreement with 10-19% difference. For the large body phantom (32-channel Tx/Rx coil), B1TIAMO matched the RF field simulations well. CONCLUSION: The results demonstrate the potential to acquire 32 accurate single channel B1+ maps for large field-of-view body imaging within only a single breath hold of 16 s at 7T UHF MRI. Magn Reson Med 79:2652-2664, 2018. (c) 2017 International Society for Magnetic Resonance in Medicine. PMID- 28994133 TI - Efficacy of perilesional and intralesional triamcinolone acetonide injections in pemphigus vulgaris lesions of the scalp: an effective therapeutic option. AB - The scalp is a common location for pemphigus vulgaris (PV), and scalp lesions may be resistant to standard treatment. Perilesional/intralesional triamcinolone acetonide (TA) injections have been used successfully to treat oropharyngeal and ocular involvement in PV. Data on the efficacy of perilesional and intralesional triamcinolone acetonide injections in scalp lesions in PV are lacking. We report two patients with immunopathologically and histopathologically confirmed PV and residual scalp lesions resistant to standard treatment, who were treated with perilesional and intralesional injections of TA 10 mg/mL. Clearance of scalp lesions was achieved after one after, respectively, one and two perilesional and intralesional injections. Perilesional and intralesional TA injections may serve as an effective and safe treatment for recalcitrant scalp lesions in pemphigus. PMID- 28994135 TI - Delusional infestation caused by pramipexole. PMID- 28994134 TI - First-line treatment in lymphomatoid papulosis: a retrospective multicentre study. AB - BACKGROUND: Data regarding response to treatment in lymphomatoid papulosis (LyP) are scarce. AIM: To assess the daily clinical practice approach to LyP and the response to first-line treatments. METHODS: This was a retrospective study enrolling 252 patients with LyP. RESULTS: Topical steroids, methotrexate and phototherapy were the most common first-line treatments, prescribed for 35%, 20% and 14% of the patients, respectively. Complete response (CR) was achieved in 48% of treated patients. Eczematous lesions significantly increased relative risk (RR) of not achieving CR (RR = 1.76; 95% CI 1.16-2.11). Overall median time to CR was 10 months (95% CI 6-13 months), and 78% of complete responders showed cutaneous relapse; both results were similar for all treatment groups (P > 0.05). Overall estimated median disease-free survival (DFS) was 11 months (95% CI 9-13 months) but DFS for patients treated with phototherapy was 23 months (95% CI 10 36 months; P < 0.03). Having the Type A LyP variant (RR = 2.04; 95% CI 0.96-4.30) and receiving a first-line treatment other than phototherapy (RR = 5.33; 95% CI 0.84-33.89) were significantly associated with cutaneous early relapse. Of the 252 patients, 31 (13%) had associated mycosis fungoides unrelated to therapeutic approach, type of LyP or T-cell receptor clonality. CONCLUSIONS: Current epidemiological, clinical and pathological data support previous results. Topical steroids, phototherapy and methotrexate are the most frequently prescribed first line treatments. Although CR and cutaneous relapse rates do not differ between them, phototherapy achieves a longer DFS. Presence of Type A LyP and use of topical steroid or methotrexate were associated with an increased risk of early relapse. PMID- 28994136 TI - The ineluctable constraints of thermodynamics in the aetiology of obesity. AB - We exploit the detail-independence feature of thermodynamics to examine issues related to the development of obesity. We adopt a 'global' approach consistent with focus on the first law of thermodynamics - namely that the metabolic energy provided by dietary foodstuffs has only three possible fates: the performance of work (be it microscopic or macroscopic), the generation of heat, or storage - primarily in the form of adipose tissue. Quantification of the energy expended, in the form of fat metabolised, during selected endurance events, reveals the inherent limitation of over-reliance on exercise as a primary agent of weight loss. This result prompts examination of various (non-exercise based) possibilities of increasing the rate of heat loss. Since these, too, give little cause for optimism, we are obliged to conclude that obesity can be prevented, or weight loss achieved, only if exercise is supplemented by reduction of food intake. PMID- 28994137 TI - Peristomal psoriasis: an intriguing new subset of psoriasis. PMID- 28994138 TI - Optic disc pit maculopathy. PMID- 28994140 TI - Fetal lung volume and pulmonary artery changes in congenital heart disease with decreased pulmonary blood flow: Quantitative ultrasound analysis. AB - BACKGROUND: It has been reported that congenital heart disease with decreased pulmonary blood flow (CHD-DPBF) may affect postnatal lung morphogenesis and function. However, there has been a lack of information regarding the impact of CHD-DPBF on prenatal fetal lung development. METHODS: Fifty-four fetuses with CHD DPBF were compared with 110 controls. Fetal lung volume (FLV) was estimated using three-dimensional ultrasonography (3D-US). Estimated fetal weight (EFW) and McGoon index (MGI) were estimated using two-dimensional ultrasonography (2D-US). RESULTS: FLV/EFW and MGI values measured using sonography for the CHD-DPBF group were significantly reduced compared to those of the control group (P < .05). Pearson correlation analysis indicated that the summed diameter of the right pulmonary artery and left pulmonary artery (RPA + LPA) measured by 2D-US correlated well with FLV measured by 3D-US. CONCLUSIONS: In our study, FLV/EFW and MGI values for fetuses with CHD-DPBF tended to be decreased and FLV was associated with RPA + LPA. We concluded that CHD-DPBF might delay fetal lung development. The summed diameter of the RPA + LPA measurement could be used as an alternative to FLV for assessing fetal lung development. PMID- 28994139 TI - Advanced imaging for the diagnosis of age-related macular degeneration: a case vignettes study. AB - BACKGROUND: The aim of this study is to evaluate the diagnosis, staging, imaging and management preferences, and the effect of advanced imaging among practising optometrists in age-related macular degeneration (AMD). METHODS: Up to 20 case vignettes (computer-based case simulations) were completed online in a computer laboratory in random order by 81 practising optometrists of Australia. Each case presented findings from a randomly selected patient seen previously at the Centre for Eye Health for a macular assessment in the following order: case history, preliminary tests and colour fundus photography. Participants were prompted to provide their diagnosis, management and imaging preference. One additional imaging result (either modified fundus photographs and infrared images, fundus autofluorescence, or optical coherence tomography [OCT]) was then provided and the questions repeated. Finally, all imaging results were provided and the questions repeated a third time. RESULTS: A total of 1,436 responses were analysed. The presence of macular pathology in AMD was accurately detected in 94 per cent of instances. The overall diagnostic accuracy of AMD was 61 per cent using colour fundus photography. This improved by one per cent using one additional imaging modality and a further four per cent using all imaging. Across all responses, a greater improvement in the diagnostic accuracy of AMD occurred following the presentation of OCT findings (versus other modalities). OCT was the most preferred imaging modality for AMD, while multimodal imaging was of greatest benefit in cases more often misdiagnosed using colour fundus photography alone. Overall, the cohort also displayed a tendency to underestimate disease severity. CONCLUSION: Despite reports that imaging technologies improve the stratification of AMD, our findings suggest that this effect may be small when applied among practising optometrists without additional or specific training. PMID- 28994142 TI - Appropriate use of echocardiography and relation to clinical decision making in both inpatients and outpatients in a developing country. AB - BACKGROUND: Use of echocardiography (echo) has exponentially increased in recent decades. Concerned about this scientific society developed appropriate use criteria (AUC). Clinical management still suffers geographical variations, and no objective data are available about echo AUC in developing countries. We aimed to evaluate (1) the appropriateness of referrals and (2) their relation to changes in clinical decision management. METHODS: Prospective analysis of referrals from January to December 2014. Appropriateness and endpoints analyzed in different time points from medical archives. ENDPOINTS: (1) change in the diagnosis, (2) indication for another method to complete the diagnosis, (3) change in clinical treatment, (4) indication for a treatment intervention, or (5) no change in management. Descriptive statistical analysis, Fisher's or chi-square tests, and Cox regression used as appropriate (significance if P < .05). RESULTS: One thousand one hundred referrals were analyzed (55.5 +/- 16.1 years, 44.6% male). 80.5% of referrals were appropriate (A), 11.2% "Rarely Appropriate" (RA), and 8.3% "May Be Appropriate" (MBA). Proportion of (A) did not differ between modalities (TTE-80.5% vs TEE-87.7% vs STR-81.2%, P = .67). (A) referrals were more related to clinical decision than (RA)+(MBA) (38.9% [A] vs 15% [RA]+[MBA], P < .001). The most frequent clinical indications of (RA) and (MBA) TTE were reevaluation of ventricular function without clinical change (AUC 10 and 11) and search of infectious endocarditis when low clinical probability (53). CONCLUSIONS: In a developing country, appropriateness of echo was similar to the United States and Europe. However, a significant proportion of referrals were still (RA) or (MBA), with no effect in clinical management. Controlling referrals 10, 11, and 53 can optimize echo use in developing countries. PMID- 28994141 TI - Potential drug-drug interactions of OMBITASVIR, PARITAPREVIR/ritonavir +/- DASABUVIR +/- ribavirin in clinical practice. AB - BACKGROUND & AIMS: Drug-drug interactions (DDIs) with ombitasvir/paritaprevir/ritonavir with or without dasabuvir and with or without ribavirin (OBV/PTV/r +/- DSV +/- RBV) are common in clinical trials. Our aim was to analyze the prevalence and management of potential DDIs and adverse events (AEs) related to DDIs in patients with chronic hepatitis C (CHC) receiving OBV/PTV/r +/- DSV +/- RBV in clinical practice. METHODS: 177 CHC patients started OBV/PTV/r +/- DSV +/- RBV in 4 Spanish hospitals and were screened for potential DDIs using the University of Liverpool database. Patients were classified according to the most serious potential DDIs at baseline and AEs during therapy. RESULTS: At least one potential DDI was found in 110 (62.1%) patients: 100 (56.5%) had at least one manageable potential DDI and 10 (5.6%) at least one contraindicated. Patients with potential DDIs were receiving a higher number of concomitant drugs (4 vs. 2, P < 0.001). Routine medication was modified at baseline due to potential DDIs in 49 (27.7%) patients. During antiviral treatment, 67 (37.9%) patients presented at least one AE. In 9 (4.5%) patients, a DDI was suspected between OBV/PTV/r +/- DSV +/- RBV and the concomitant drug, requiring antiviral discontinuation in 4 patients. CONCLUSIONS: Potential DDIs are frequent with OBV/PTV/r +/- DSV +/- RBV, although a change in baseline medication is made in only one-quarter of patients. More than half of potential DDIs were only followed, and only 5% of patients developed AEs in which the implication of DDIs could not be excluded. PMID- 28994143 TI - Correlates of physical activity among depressed older people in six low-income and middle-income countries: A community-based cross-sectional study. AB - OBJECTIVE: Despite the benefits of physical activity (PA) in older people with depression, many do not comply with the International PA guidelines. Thus, we investigated what factors influence PA participation among 915 community-dwelling older adults (aged >=65 years) with depression in 6 low-income and middle-income countries (LMICs). METHODS: Cross-sectional data were analyzed from the World Health Organization's Study on Global Ageing and Adult Health. The sample was restricted to those with DSM-IV depression or receiving depression treatment in the last 12 months. PA was assessed by the Global Physical Activity Questionnaire. Participants were dichotomized into low (ie, not meeting 150 minutes of moderate PA per week) and moderate-to-high physically active groups. Associations between PA and a range of correlates were examined using multivariable logistic regressions. RESULTS: The prevalence of low PA was 40.4% (95%CI = 34.8%-46.1%). After adjusting for age, sex, and country, larger household size and unemployment were significant sociodemographic correlates of low PA. Former smoking (vs never), anxiety, mild cognitive impairment (MCI), lower body mass index, bodily pain, asthma, chronic back pain, chronic obstructive pulmonary disease, hearing problems, stroke, slow gait, poor self rated health, higher levels of disability, and lower levels of social cohesion were identified as significant negative correlates of PA. CONCLUSIONS: The current data provide guidance for future interventions across LMICs to assist older people with depression engage in regular PA. The promotion of social cohesion may increase the efficacy of future public health initiatives, while from a clinical perspective, somatic co-morbidities, MCI, pain, and slow gait need to be considered. PMID- 28994144 TI - Stereoacuity measurement using a phoropter combined with two 4K smartphones. AB - PURPOSE: To evaluate stereoacuity using a combination of a phoropter and two 4K smartphones. METHODS: A stereopsis measurement system was established using a phoropter (Topcon VT-10) and two Sony 4K smartphones (Sony Xperia Z5 Premium Dual E6883). A total of 154 subjects (69 children and 85 adults) were enrolled for evaluation using this system and subsequent comparison with the Fly Stereo Acuity test. RESULTS: There was a high level of agreement between the two methods using Bland-Altman statistical analysis (children group, 95 per cent limits of agreement +/-0.14 log arcseconds [arcsec]; adult group, 95 per cent limits of agreement +/-0.13 log arcsec). CONCLUSION: The closely spaced pixels of a 4K smartphone display enable measurement of stereoacuity at a relatively short distance. The flexibility and versatility of the mobile test system are likely to be useful in clinical practice. PMID- 28994145 TI - Adherence to Barcelona Clinic Liver Cancer guidelines in field practice: Results of Progetto Epatocarcinoma Campania. AB - BACKGROUND AND AIM: The Barcelona Clinic Liver Cancer (BCLC) algorithm is the standard system for clinical management of hepatocellular carcinoma (HCC). Data on adherence to this therapeutic paradigm are scarce. This field practice study aimed to provide a description of HCC cirrhotic patients in Southern Italy, to evaluate the adherence to BCLC guidelines and its impact on patients' survival. METHODS: We analyzed the region-wide Italian database of Progetto Epatocarcinoma Campania, which includes data of HCC cirrhotic patients, prospectively collected from January 2013 to December 2015 in 16 regional centers. RESULTS: Overall, 1008 HCC patients were enrolled: 70.6% patients received therapies recommended by BCLC algorithm, while 29.4% underwent different treatments. Among patients who were treated in adherence to guidelines, a higher rate of diagnosis on surveillance programs, better liver function, lower rate of alpha-fetoprotein > 200 ng/mL, more early-stage and monofocal HCC, lower frequency of nodules > 5 cm, portal vein thrombosis and metastases were observed. The overall survival was evaluated according to HCC stage and no differences between groups and patients managed differently were found. The multivariate analysis showed that non-adherence to treatment guidelines was independently associated to the BCLC stage B, Child-Pugh classes B and C, and the presence of neoplastic thrombosis and metastases. CONCLUSION: Adherence to BCLC algorithm in field practice was high in early and end-stage HCC patients, but it was poor in intermediate and advanced patients. PMID- 28994146 TI - Congenital unruptured aneurysm of sinus of Valsalva, quadricuspid aortic valve, and ascending aortic aneurysm associated with genetic leukoencephalopathy in an infant: A new syndrome? AB - We report a 15-month-old female with unruptured noncoronary sinus of Valsalva anreurysm (SOVA) associated with quadricuspid aortic valve, ascending aortic aneurysm (AAA), moderate aortic insufficiency, mild mitral insufficiency, genetic leukoencepaholpathy, developmental delay and mild mixed aminoaciduria. She was referred for evaluation of a cardiac murmur. Initial echocardiographic examination showed the aneurysm as a round cyst in the right atrium which changed in size during systole and diastole. As to the best of our knowledge, this is the first report of association of SOVA, quadricuspid aortic valve, AAA and genetic leukoencephalopathy in an infant. These associations may suggest a new syndrome. We describe the echocardiographic and computed tomographic angiography findings. We also review 641 cases in the literature and the current six classification systems for SOVA. PMID- 28994147 TI - Reduction effect of the quantity of radiation exposure and contrast media by image support system in transarterial chemoembolization for the treatment of hepatocellular carcinoma. AB - BACKGROUND AND AIM: We confirmed the clinical utility of a three-dimensional navigation system during transarterial chemoembolization. METHODS: We evaluated 128 tumors in 91 patients enrolled between May 2015 and August 2016. We evaluated the accuracy of the three-dimensional navigation imaging system for all tumors. We compared the patients who were able to undergo route detection using three dimensional navigation with previously treated patients who underwent transarterial chemoembolization without using three-dimensional navigation (n = 21). For 38 patients who underwent super-selective microcatheter insertion after a feeding artery was identified by three-dimensional navigation, we confirmed the relationship between the tumors and contrasted liver parenchyma and divided the computed tomography hepatic arteriography findings into four grades. Grade 1: an overlap of > 5 mm, grade 2: an overlap between 0 and 5 mm, grade 3: the borders of the tumor within the liver parenchyma but in contact with the edges, and grade 4: a tumor outside the borders of the liver parenchyma. RESULTS: Using the three dimensional navigation system, we identified a tumor-feeding artery in 125/128 tumors (97.6%). Furthermore, this system allowed us to significantly reduce the volume of contrast media and the radiation exposure dose in patients undergoing an evaluation. We identified 15 grade 1 tumors (39.5%), 3 grade 2 tumors (7.9%), 11 grade 3 tumors (28.9%), and 9 grade 4 tumors (23.7%) according to our definitions. CONCLUSION: The three-dimensional navigation is useful not only for patients but also for surgeons who have relatively little experience. PMID- 28994148 TI - LincRNA-p21 suppresses development of human prostate cancer through inhibition of PKM2. AB - OBJECTIVES: Previously, we found that long intergenic non-coding RNA-p21 (lincRNA p21) inhibited the development of human prostate cancer. However, the underlying molecular mechanisms are poorly understood. Here, we attempted to investigate the downstream targets of lincRNA-p21 in prostate cancer. MATERIALS AND METHODS: Expression of lincRNA-p21 and PKM2 was determined by qRT-PCR and Western blot. Lentivirus expressing shPKM2 or shCtrl was used to explore the role of PKM2 on the enhanced cell proliferation and glycolysis of lincRNA-p21-silenced prostate cancer cells. A xenograft mouse model was performed to investigate the effect of PKM2 suppression, glycolytic or mammalian target of rapamycin (mTOR) inhibitor on the tumorigenic capacity of lincRNA-p21-silenced prostate cancer cells. RESULTS: We revealed that lincRNA-p21 silencing in DU145 and LNCaP cells induced up regulation of PKM2 and activation of glycolysis, which could be reversed by PKM2 knockdown or rapamycin treatment. We also found that the proliferation and tumorigenesis of lincRNA-p21-silenced prostate cancer cells were significantly inhibited after knocking down PKM2. 3-bromopyruvate (3-Brpa) or rapamycin treatment largely decreased the tumour burden. Importantly, PKM2 expression was inversely correlated with the lincRNA-p21 level and the survival of prostate cancer patients. CONCLUSIONS: We demonstrated that lincRNA-p21 blunted the prostate cancer cell proliferation and tumorigenic capacity through down regulation of PKM2. Therefore, targeting PKM2 or glycolysis might be a therapeutic strategy in prostate cancer patients with lowly expressed lincRNA p21. PMID- 28994150 TI - Unraveling the Mystery of the Blue Fog: Structure, Properties, and Applications of Amorphous Blue Phase III. AB - The amorphous blue phase III of cholesteric liquid crystals, also known as the "blue fog," are among the rising stars in materials science that can potentially be used to develop next-generation displays with the ability to compete toe-to toe with disruptive technologies like organic light-emitting diodes. The structure and properties of the practically unobservable blue phase III have eluded scientists for more than a century since it was discovered. This progress report reviews the developments in this field from both fundamental and applied research perspectives. The first part of this progress report gives an overview of the 130-years-long scientific tour-de-force that very recently resulted in the revelation of the mysterious structure of blue phase III. The second part reviews progress made in the past decade in developing electrooptical, optical, and photonic devices based on blue phase III. The strong and weak aspects of the development of these devices are underlined and criticized, respectively. The third- and-final part proposes ideas for further improvement in blue phase III technology to make it feasible for commercialization and widespread use. PMID- 28994149 TI - Enzyme-Free Colorimetric Detection of Cu2+ by Utilizing Target-Triggered DNAzymes and Toehold-Mediated DNA Strand Displacement Events. AB - A new enzyme-free system for colorimetric Cu2+ detection, which relies on target triggered DNAzymes and toehold-mediated DNA strand-displacement circuits, is described. The system employs a DNAzyme designed to undergo self-cleavage in the presence of Cu2+ and release a catalyst strand that triggers a sequential toehold mediated strand displacement reaction. This event leads to the release of a split G-quadruplex DNAzyme strand that is initially caged and inactivated by a blocker strand. A fuel strand is further incorporated for the recycling of the catalyst strand to promote another toehold-mediated strand displacement event, which consequently produces a large number of active split G-quadruplex DNAzymes. By employing this design principle, target Cu2+ was very successfully identified with a detection limit of 1.31 nm based on the distinct colorimetric signal developed by the oxidation of 2,2'-azino-bis(3-ethylbenzothiazoline)-6-sulfonic acid promoted by the peroxidase mimicking activity of the released G-quadruplex DNAzymes. Finally, the practical capability of this sensing system was very successfully demonstrated by its use to reliably determine Cu2+ in tap water. PMID- 28994151 TI - Negative hepatic computed tomographic attenuation pattern in a dog with vacuolar hepatopathy and hepatic fat accumulation secondary to cushing's syndrome. AB - This report describes an unusual computed tomographic (CT) hepatic pattern, characterized by negative attenuation values (from -19.59 to -28.85 Hounsfield Units, HU) in a canine patient with severe Cushing's syndrome. Attenuation values of the splenic parenchyma (63.26 HU) and abdominal fat (-118.34 HU) were within normal limits. The negative hepatic attenuation values allowed a CT diagnosis of severe hepatic fatty infiltration that was subsequently confirmed by tissue-core biopsy and histopathological examination. PMID- 28994152 TI - Genomics of adaptive divergence with chromosome-scale heterogeneity in crossover rate. AB - Genetic differentiation between divergent populations is often greater in chromosome centres than peripheries. Commonly overlooked, this broadscale differentiation pattern is sometimes ascribed to heterogeneity in crossover rate and hence linked selection within chromosomes, but the underlying mechanisms remain incompletely understood. A literature survey across 46 organisms reveals that most eukaryotes indeed exhibit a reduced crossover rate in chromosome centres relative to the peripheries. Using simulations of populations diverging into ecologically different habitats through sorting of standing genetic variation, we demonstrate that such chromosome-scale heterogeneity in crossover rate, combined with polygenic divergent selection, causes stronger hitchhiking and especially barriers to gene flow across chromosome centres. Without requiring selection on new mutations, this rapidly leads to elevated population differentiation in the low-crossover centres relative to the high-crossover peripheries of chromosomes ("Chromosome Centre-Biased Differentiation", CCBD). Using simulated and empirical data, we then show that strong CCBD between populations can provide evidence of polygenic adaptive divergence with a phase of gene flow. We further demonstrate that chromosome-scale heterogeneity in crossover rate impacts analyses beyond that of population differentiation, including the inference of phylogenies and parallel adaptive evolution among populations, the detection of genetic loci under selection, and the interpretation of the strength of selection on genomic regions. Overall, our results call for a greater appreciation of chromosome-scale heterogeneity in crossover rate in evolutionary genomics. PMID- 28994153 TI - X-ray elemental mapping techniques for elucidating the ecophysiology of hyperaccumulator plants. AB - Contents Summary 432 I. Introduction 433 II. Preparation of plant samples for X ray micro-analysis 433 III. X-ray elemental mapping techniques 438 IV. X-ray data analysis 442 V. Case studies 443 VI. Conclusions 446 Acknowledgements 449 Author contributions 449 References 449 SUMMARY: Hyperaccumulators are attractive models for studying metal(loid) homeostasis, and probing the spatial distribution and coordination chemistry of metal(loid)s in their tissues is important for advancing our understanding of their ecophysiology. X-ray elemental mapping techniques are unique in providing in situ information, and with appropriate sample preparation offer results true to biological conditions of the living plant. The common platform of these techniques is a reliance on characteristic X rays of elements present in a sample, excited either by electrons (scanning/transmission electron microscopy), protons (proton-induced X-ray emission) or X-rays (X-ray fluorescence microscopy). Elucidating the cellular and tissue-level distribution of metal(loid)s is inherently challenging and accurate X-ray analysis places strict demands on sample collection, preparation and analytical conditions, to avoid elemental redistribution, chemical modification or ultrastructural alterations. We compare the merits and limitations of the individual techniques, and focus on the optimal field of applications for inferring ecophysiological processes in hyperaccumulator plants. X-ray elemental mapping techniques can play a key role in answering questions at every level of metal(loid) homeostasis in plants, from the rhizosphere interface, to uptake pathways in the roots and shoots. Further improvements in technological capabilities offer exciting perspectives for the study of hyperaccumulator plants into the future. PMID- 28994154 TI - Concealing a shiny facial skin appearance by an Aerogel-based formula. In vitro and in vivo studies. AB - OBJECTIVE: To explore, in vitro and in vivo, the potential interest of an Aerogel based formula, in concealing a naturally shiny facial skin. METHODS: In vitro, various formulae and ingredients were applied as a thin film onto contrast plates and studied through measuring the shine induced following pump spraying of a mixture of oleic acid and mineral water as a sebum/sweat mix model. In such a test, an Aerogel ingredient led to very positive results. In vivo, two different formulae with various concentrations of Aerogel were randomly tested on half side of the face vs. bare side of Chinese women, under some provocative environmental conditions, known to enhance facial shine. These conditions comprised a normal activity under a hot and highly humid summer time followed - or not - by a hamam session. Both studies included comparative evaluations using a half-face procedure (treated/untreated or vehicle). In the first case, evaluations were quantitatively carried out, whereas the second one was based on a quantitative self-evaluations from standardized full-face photographs RESULTS: In vitro, the tested Aerogel, incorporated at 1% or 2% concentration in a common O/W cosmetic emulsion, shows an immediate light scattering effect, thereby masking shine. Such effect appears of much higher amplitude than that of two other tested particulate ingredients (Talc and Perlite). A noticeable remanence of anti-shine effect was confirmed in vivo in extreme conditions. The latter was self-perceived by all participants in the second study. This result is likely related to the super hydrophobic behaviour of the Aerogel. CONCLUSION: As cosmetic ingredient, this new Aerogel appears as a highly promising ingredient for concealing the facial skin shine, a source of complaint from many consumers living in hot and humid regions. PMID- 28994156 TI - Synthesis of nano-sized hydrogen phosphate-imprinted polymer in acetonitrile/water mixture and its use as a recognition element of hydrogen phosphate selective all-solid state potentiometric electrode. AB - Herein, a new recipe is introduced for the preparation of hydrogen phosphate ion imprinted polymer nanoparticles (nano-IIP) in acetonitrile/water (63.5:36.5) using phosphoric acid as the template. The nano-IIP obtained was used as the recognition element of a carbon paste potentiometric sensor. The IIP electrode showed a Nernstian response to hydrogen phosphate anion; whereas, the non imprinted polymer (NIP)-based electrode had no considerable sensitivity to the anion. The presence of both methacrylic acid and vinyl pyridine in the IIP structure, as well as optimization of the functional monomers-template proportion, was found to be important to observe the sensing capability of the IIP electrode. The nano-IIP electrode showed a dynamic linear range of 1 * 10-5 1 * 10-1 mol L-1, Nernstian slope of 30.6 +/- (0.5) mV decade -1 , response time of 25 seconds, and detection limit of 4.0 * 10-6 mol L-1 . The utility of the electrodes was checked by potentiometric titration of hydrogen phosphate with La3+ solution. PMID- 28994155 TI - Regenerable-Catalyst-Aided, Opened to Air and Sunlight-Driven "CuAAC&ATRP" Concurrent Reaction for Sequence-Controlled Copolymer. AB - An ideal stimuli-responsive controlled/living radical polymerization should have the ability to manipulate the reaction through spatiotemporal "on/off" controls, achieving the polymerization under fully open conditions and allowing for precise control over macromolecular architecture with defined molecular weights and monomer sequence. In this contribution, the photo (sunlight)-induced electron transfer atom transfer radical-polymerization (PET-ATRP) can be realized to be reversibly activated and deactivated under fully open conditions utilizing one component copper(II) thioxanthone carboxylate as multifunctional photocatalyst and oxygen scavenger. The polymerization behaviors are investigated, presenting controlled features with first-order kinetics and linear relationships between molecular weights and monomer conversions. More importantly, "CuAAC&ATRP" concurrent reaction combining PET-ATRP, photodriven deoxygenation, and photoactivated CuAAC click reaction is successfully employed to synthesize the sequence-defined multiblock functional copolymers, in which the iterative monomer additions can be easily manipulated under fully open conditions. PMID- 28994157 TI - Genome-wide association study and annotating candidate gene networks affecting age at first calving in Nellore cattle. AB - We performed a genome-wide mapping for the age at first calving (AFC) with the goal of annotating candidate genes that regulate fertility in Nellore cattle. Phenotypic data from 762 cows and 777k SNP genotypes from 2,992 bulls and cows were used. Single nucleotide polymorphism (SNP) effects based on the single-step GBLUP methodology were blocked into adjacent windows of 1 Megabase (Mb) to explain the genetic variance. SNP windows explaining more than 0.40% of the AFC genetic variance were identified on chromosomes 2, 8, 9, 14, 16 and 17. From these windows, we identified 123 coding protein genes that were used to build gene networks. From the association study and derived gene networks, putative candidate genes (e.g., PAPPA, PREP, FER1L6, TPR, NMNAT1, ACAD10, PCMTD1, CRH, OPKR1, NPBWR1 and NCOA2) and transcription factors (TF) (STAT1, STAT3, RELA, E2F1 and EGR1) were strongly associated with female fertility (e.g., negative regulation of luteinizing hormone secretion, folliculogenesis and establishment of uterine receptivity). Evidence suggests that AFC inheritance is complex and controlled by multiple loci across the genome. As several windows explaining higher proportion of the genetic variance were identified on chromosome 14, further studies investigating the interaction across haplotypes to better understand the molecular architecture behind AFC in Nellore cattle should be undertaken. PMID- 28994158 TI - The myths of medication adherence. PMID- 28994160 TI - The use of accelerometer to measure sleeping posture of beef cows. AB - Sleep is one of the essential behaviors for mammals. The aims of this study were to validate the use of accelerometer for measuring sleeping posture of cattle. Duration of sleeping posture of seven Japanese Black cows from 19.00 to 07.00 hours was measured by both accelerometer and video, and a total of 67 accelerometer and video measurement sets were collected. We calculated Cohen's kappa coefficient between accelerometer and video measurements and 91.5% of the kappa-values were >0.80. Intra- and inter-observer coefficient of variance showed that specific acceleration waveform patterns of sleeping posture could be easily and accurately detected by independent observers. There were no significant differences in the frequency of sleeping posture occurrences between accelerometer and video measurements. We compared averaged sleeping posture bout, and the total sleeping posture time between accelerometer and video measurements using regression. In each trait, the slope was close to 1 and the intercept was not different from 0, which showed a strong agreement between accelerometer and video measurements. This shows that an accelerometer could accurately detect sleeping postures of cattle. We conclude that adequate measurements of sleeping postures can be made using an accelerometer. PMID- 28994161 TI - Vitrification of bovine matured oocytes and blastocysts in a paper container. AB - In the present study, we aimed to determine the applicability of a paper container for the vitrification of in vitro matured (IVM) bovine oocytes. In experiment 1, IVM oocytes were exposed to vitrification solution (20% dimethylsulfoxide (DMSO), 20% ethylene glycol (EG), and 5 mol/L sucrose), using a two-step method, for 30 s; loaded onto either a paper container or Cryotop; and stored in liquid nitrogen. No significant difference (P < 0.05) in the survival and blastocyst formation rates after in vitro vitrification was observed between the paper container and Cryotop. In experiment 2, IVM oocytes were exposed to either a two- or three-step vitrification solution. The three-step vitrification solution was not significantly different from the two-step solution in terms of oocyte survival, cleavage and blastocyst rates. In experiment 3, in vitro produced blastocysts were graded according to the manual of the International Embryo Transfer Society (grades 1 and 2) and vitrified using the two- and three step methods. For grade 2 blastocysts, the three-step method showed significantly higher (P < 0.05) survival and hatched blastocyst rates than the two-step method, whereas for grade 1 blastocysts, no significant difference was observed. In conclusion, the paper device and three-step technique are suitable for oocytes and embryo vitrification. PMID- 28994159 TI - Calcium and electrical dynamics in lymphatic endothelium. AB - KEY POINTS: Endothelial cell function in resistance arteries integrates Ca2+ signalling with hyperpolarization to promote relaxation of smooth muscle cells and increase tissue blood flow. Whether complementary signalling occurs in lymphatic endothelium is unknown. Intracellular calcium and membrane potential were evaluated in endothelial cell tubes freshly isolated from mouse collecting lymphatic vessels of the popliteal fossa. Resting membrane potential measured using intracellular microelectrodes averaged ~-70 mV. Stimulation of lymphatic endothelium by acetylcholine or a TRPV4 channel agonist increased intracellular Ca2+ with robust depolarization. Findings from Trpv4-/- mice and with computational modelling suggest that the initial mobilization of intracellular Ca2+ leads to influx of Ca2+ and Na+ through TRPV4 channels to evoke depolarization. Lymphatic endothelial cells lack the Ca2+ -activated K+ channels present in arterial endothelium to generate endothelium-derived hyperpolarization. Absence of this signalling pathway with effective depolarization may promote rapid conduction of contraction along lymphatic muscle during lymph propulsion. ABSTRACT: Subsequent to a rise in intracellular Ca2+ ([Ca2+ ]i ), hyperpolarization of the endothelium coordinates vascular smooth muscle relaxation along resistance arteries during blood flow control. In the lymphatic vasculature, collecting vessels generate rapid contractions coordinated along lymphangions to propel lymph, but the underlying signalling pathways are unknown. We tested the hypothesis that lymphatic endothelial cells (LECs) exhibit Ca2+ and electrical signalling properties that facilitate lymph propulsion. To study electrical and intracellular Ca2+ signalling dynamics in lymphatic endothelium, we excised collecting lymphatic vessels from the popliteal fossa of mice and removed their muscle cells to isolate intact LEC tubes (LECTs). Intracellular recording revealed a resting membrane potential of ~-70 mV. Acetylcholine (ACh) increased [Ca2+ ]i with a time course similar to that observed in endothelium of resistance arteries (i.e. rapid initial peak with a sustained 'plateau'). In striking contrast to the endothelium-derived hyperpolarization (EDH) characteristic of arteries, LECs depolarized (>15 mV) to either ACh or TRPV4 channel activation. This depolarization was facilitated by the absence of Ca2+ -activated K+ (KCa ) channels as confirmed with PCR, persisted in the absence of extracellular Ca2+ , was abolished by LaCl3 and was attenuated ~70% in LECTs from Trpv4-/- mice. Computational modelling of ion fluxes in LECs indicated that omitting K+ channels supports our experimental results. These findings reveal novel signalling events in LECs, which are devoid of the KCa activity abundant in arterial endothelium. Absence of EDH with effective depolarization of LECs may promote the rapid conduction of contraction waves along lymphatic muscle during lymph propulsion. PMID- 28994162 TI - Effect of probiotics on perinatal outcome in patients at high risk of preterm birth. AB - AIM: Recent reports have shown lower levels of Clostridium and higher levels of Lactobacillales in the intestinal microbiota in preterm birth patients compared to term birth patients. However, the influence of probiotics on perinatal status has not been elucidated. The aim of our study was to evaluate the effects of probiotics on perinatal outcomes. METHODS: We retrospectively evaluated the effects of oral probiotics on perinatal outcome in patients at high risk of preterm birth. Probiotics containing Streptococcus faecalis, Clostridium butyricum and Bacillus mesentericus were administered for prophylaxis of bacterial vaginosis or treatment of constipation starting at 12.5 +/- 4.1 weeks until delivery. Patients not administered probiotics were defined as the non probiotics group. Between these two groups, perinatal outcomes including gestational age at birth, birth weight, chorioamnionitis or funisitis and preterm birth before 32 weeks were compared. In addition, multivariate regression analyses were performed to evaluate factors influencing preterm birth before 32 weeks, chorioamnionitis/funisitis and normal vaginal flora. RESULTS: The probiotics group showed longer gestation, higher birth weight, lower rates of chorioamnionitis and higher rates of normal vaginal flora compared to the non probiotics group. Multivariate regression analysis showed that probiotics significantly suppressed preterm birth before 32 weeks and tended to suppress chorioamnionitis/funisitis. The adjusted odds ratios (95% confidence interval) for preterm birth before 32 weeks and chorioamnionitis/funisitis were 0.05 (0.01 0.71) and 0.07 (0.01-1.03), respectively. CONCLUSIONS: Oral probiotics containing Clostridium had a significant effect on the prevention of preterm birth before 32 weeks of gestation. PMID- 28994163 TI - Responses of phenology and biomass production of boreal fens to climate warming under different water-table level regimes. AB - Climate change affects peatlands directly through increased air temperatures and indirectly through changes in water-table level (WL). The interactions of these two still remain poorly known. We determined experimentally the separate and interactive effects of temperature and WL regime on factors of relevance for the inputs to the carbon cycle: plant community composition, phenology, biomass production, and shoot:root allocation in two wet boreal sedge-dominated fens, "southern" at 62 degrees N and "northern" at 68 degrees Nu. Warming (1.5 degrees C higher average daily air temperature) was induced with open-top chambers and WL drawdown (WLD; 3-7 cm on average) by shallow ditches. Total biomass production varied from 250 to 520 g/m2 , with belowground production comprising 25%-63%. Warming was associated with minor effects on phenology and negligible effects on community composition, biomass production, and allocation. WLD clearly affected the contribution of different plant functional types (PFTs) in the community and the biomass they produced: shrubs benefited while forbs and mosses suffered. These responses did not depend on the warming treatment. Following WLD, aboveground biomass production decreased mainly due to reduced growth of mosses in the southern fen. Aboveground vascular plant biomass production remained unchanged but the contribution of different PFTs changed. The observed changes were also reflected in plant phenology, with different PFTs showing different responses. Belowground production increased following WLD in the northern fen only, but an increase in the contributions of shrubs and forbs was observed in both sites, while sedge contribution decreased. Moderate warming alone seems not able to drive significant changes in plant productivity or community composition in these wet ecosystems. However, if warming is accompanied by even modest WL drawdown, changes should be expected in the relative contribution of PFTs, which could lead to profound changes in the function of fens. Consequently, hydrological scenarios are of utmost importance when estimating their future function. PMID- 28994165 TI - A Demonstrative Tactile Method to Guide Mandibular Movements. AB - Dental practitioners often require patients to perform specific mandibular movements (protrusive, retrusive, and lateral) in order to make centric relation and eccentric records. Occasionally, patients are unable to comprehend and perform the desired movements, even after repeated instructions. This article describes a quick, simple, and easy-to-follow technique to help guide patients with their mandibular movements. PMID- 28994164 TI - Utilization of increased risk for transmission of infectious disease donor organs in solid organ transplantation: Retrospective analysis of disease transmission and safety. AB - The inadequate supply of transplantable organs necessitates new approaches to organ availability. Serologies and nucleic acid testing (NAT) for hepatitis C virus (HCV), hepatitis B virus (HBV), and human immunodeficiency virus (HIV) are used in microbiologic screening of potential organ donors. Organs from donors considered at "high risk" (Centers for Disease Control and Prevention, CDC 1994) or "increased risk" (U.S. Public Health Service, PHS 2013) for transmission of viral infection to recipients may provide an expanded source of organs for transplantation. We review a single-center experience with 257 adult organ recipients of organs from donors meeting either CDC 1994 or PHS 2013 risk criteria between 2011 and 2016. Tracking these transplants required modification of the Transplant Center electronic database to identify all recipients of increased-risk donor (IRD) organs, documentation of informed consent, and microbiologic testing data. No transmissions of HIV, HBV, or HCV were identified by NAT or clinically. Nine patients developed positive serologic assays for one of the tested viruses; all recipients were retested and remain negative by NAT. Notably, post-transplant HBV core serologies reverted to negative on re-testing; these positive serologies are likely false positives caused by receipt of blood products. Use of IRD organs can be performed safely with appropriate informed consent and rigorous pre- and post-transplant microbiological testing. PMID- 28994166 TI - Newer treatments of psoriasis regarding IL-23 inhibitors, phosphodiesterase 4 inhibitors, and Janus kinase inhibitors. AB - The rapid progress of genetic engineering furthermore opens up new prospects in the therapy of this difficult-to-treat disease. IL-23 inhibitors, phosphodiesterase 4 (PDE4) inhibitors, and Janus kinase (JAK) inhibitors are currently encouraging further research. Two drugs which are IL-23 inhibitors are now in phase III of clinical trials. The aim of the action of both drugs is selective IL-23 inhibition by targeting the p19 subunit. Guselkumab is a fully human monoclonal antibody. Tildrakizumab is a humanized monoclonal antibody, which also belongs to IgG class and is targeted to subunit p19 of interleukin 23 (IL-23). Phosphodiesterase inhibitors exert an anti-inflammatory action and their most common group is the PDE4 family. PDE4 inhibits cAMP, which reduces the inflammatory response of the pathway of Th helper lymphocytes, Th17, and type 1 interferon which modulates the production of anti-inflammatory cytokines such as IL-10 interleukins. The Janus kinase (JAK) signaling pathway plays an important role in the immunopathogenesis of psoriasis. Tofacitinib suppresses the expression of IL-23, IL-17A, IL-17F, and IL-22 receptors during the stimulation of lymphocytes. Ruxolitinib is a selective inhibitor of JAK1 and JAK2 kinases and the JAK-STAT signaling pathway. This article is a review of the aforementioned drugs as described in the latest available literature. PMID- 28994167 TI - Optimization and physicochemical properties of nutritional protein isolate from pork liver with ultrasound-assisted alkaline extraction. AB - The aim of this study was to investigate the optimal conditions of ultrasound assisted alkaline extraction (UAAE) on pork liver protein isolate (UPLPI) and its physico-chemical properties. Response surface methodology was used to determine the optimal conditions for UAAE, which were at ultrasonic power 265 W, ultrasonic time 42 min, NaOH concentration 0.80%, temperature 50 degrees C, and solvent/raw material ratio 70. The extraction yield and efficiency of UPLPI were significantly improved over the conventional alkaline extraction (PLPI). The results of amino acid composition showed that UAAE could increase serine (36.5 g/kg), arginine (38.1 g/kg), alanine (37.5 g/kg), proline (48.7 g/kg), phenylalanine (55.6 g/kg) and lysine (47.2 g/kg) elution amount. The changes in fourier transform infrared spectra indicated unfolding and destruction of the protein structure in UPLPI. The differential scanning calorimetry analysis presented UPLPI with a slightly lower onset and peak denaturation temperature over PLPI. Surface hydrophobicity increased and the microstructures presented larger and more pores of UPLPI, therefore, it had better in vitro digestibility than PLPI. Therefore, UPLPI might have a potential application prospect in the food field due to its changes on molecular structure as well as on the microstructure of protein by UAAE. PMID- 28994168 TI - Hair cortisol levels of lactating dairy cows in cold- and warm-temperate regions in Japan. AB - We compared the hair cortisol levels of lactating dairy cows in a cold- and a warm-temperate region out of four climatic zones in Japan. We simultaneously investigated the effects of calving number, lactation period and month of hair sampling. Hair of nine Holstein lactating cows chosen from each region (i.e. 18 cows per sampling) was sampled in March, June, September and December. Number of calvings (1, 2, >=3) and lactation duration (early: <100, middle: 101-200, and late: >201 days) were balanced between regions. Cortisol was extracted from hair by methanol, and its level was determined with a cortisol immunoassay kit. A multi-way analysis of variance revealed that the effects of month of hair sampling (P < 0.001) and its combination with region (P < 0.05) were significant. In a multiple comparison test, significant differences (P < 0.01) in hair cortisol level (pg/mg of hair) were found between June (13.0 +/- 1.0) and the other 3 months, and between September (1.6 +/- 0.2) and December (4.5 +/- 0.3). The rise in cortisol level from March to June was more intense in the cold temperate region. These results demonstrate the necessity of considering seasonal variations in each climatic region when we use hair cortisol level as an indicator of stress. PMID- 28994169 TI - Methotrexate-induced pneumonia: A dermatologist wake up call. PMID- 28994170 TI - Why decadal to century timescale palaeoclimate data are needed to explain present day patterns of biological diversity and change. AB - The current distribution of species, environmental conditions and their interactions represent only one snapshot of a planet that is continuously changing, in part due to human influences. To distinguish human impacts from natural factors, the magnitude and pace of climate shifts, since the Last Glacial Maximum, are often used to determine whether patterns of diversity today are artefacts of past climate change. In the absence of high-temporal resolution palaeoclimate reconstructions, this is generally done by assuming that past climate change occurred at a linear pace between widely spaced (usually, >=1,000 years) climate snapshots. We show here that this is a flawed assumption because regional climates have changed significantly across decades and centuries during glacial-interglacial cycles, likely causing rapid regional replacement of biota. We demonstrate how recent atmosphere-ocean general circulation model (AOGCM) simulations of the climate of the past 21,000 years can provide credible estimates of the details of climate change on decadal to centennial timescales, showing that these details differ radically from what might be inferred from longer timescale information. High-temporal resolution information can provide more meaningful estimates of the magnitude and pace of climate shifts, the location and timing of drivers of physiological stress, and the extent of novel climates. They also produce new opportunities to directly investigate whether short-term climate variability is more important in shaping biodiversity patterns rather than gradual changes in long-term climatic means. Together, these more accurate measures of past climate instability are likely to bring about a better understanding of the role of palaeoclimatic change and variability in shaping current macroecological patterns in many regions of the world. PMID- 28994171 TI - Brain abscesses caused by Cladophialophora bantiana in a lung transplant patient: A case report and review of the literature. AB - Cladophialophora bantiana brain abscesses are rare, but are frequently and quickly lethal in transplanted patients. We report the case of a 63-year-old man who had undergone lung transplantation for chronic obstructive pulmonary disease and presented with headaches and a neurological deficit. Magnetic resonance imaging revealed multiple brain abscesses. C. bantiana was identified by DNA sequencing performed directly on cerebral tissue obtained by surgical biopsy. After 6 months of antifungal treatment, the brain abscesses were replaced by ischemic sequelae. The patient died suddenly 2 months later from a pulmonary bacterial infection. This is the second reported case of C. bantiana brain abscesses in a lung transplant recipient, to our knowledge, who experienced a long survival period with medical antifungal treatment alone. We review the literature and discuss our treatment. PMID- 28994172 TI - Ultraviolet filters in hair-care products: a possible link with frontal fibrosing alopecia and lichen planopilaris. PMID- 28994173 TI - Looking for Japan's missing third baby boom. AB - AIM: High-income countries are now experiencing a decline in fertility. After experiencing baby booms in 1947-1949 and 1971-1974, Japan's population has been decreasing since 2015. In an attempt to predict the next baby boom, we searched for any upward demographic trends occurring after 1974. METHODS: We analyzed time trends of the numbers and rates of live births, stillbirths and induced abortions using Japanese government data from 1975 to 2014. We then selected two birth cohorts: the first baby boomers who were 0-4 years old in 1950, and the second baby boomers who were 0-4 years old in 1975, and analyzed their rates of live births, stillbirths, and abortions by five-year age groups. RESULTS: There was no upswing in the numbers of births, stillbirths, or induced abortions; however, the abortion rate increased during 1996-2002. Compared with the first baby boomer cohort, the second baby boomer cohort had half the peak live birth rate for the same age group (25-29 years old), and half the peak rate of abortions, with a shift toward a younger age group (20-24). CONCLUSIONS: This analysis of Japanese fertility trends derived from all pregnancy outcomes showed no upward trend in fertility in Japan since 1974. PMID- 28994175 TI - Mild Reduction of Phosphine Oxides with Phosphites To Access Phosphines. AB - A new method for the iodine-catalyzed reduction of phosphine oxides with phosphites at room temperature is reported. The mild reaction conditions, scalability, and simple purification requirements render it a method of choice for the large-scale production and facile regeneration of a variety of phosphines. Mechanistic studies, supported by DFT calculations of the oxygen transfer between the starting phosphine oxide and the phosphite reagent, are also presented. Such transmutations of phosphorus species were previously unknown. PMID- 28994174 TI - Subcutaneous phaeohyphomycosis in kidney transplant recipients: A series of seven cases. AB - BACKGROUND: Superficial and deep fungal infections are more frequent in transplant recipients primarily because of the failure of cell-mediated immunity and lesser amount of antigen-presenting Langerhans cells in their epidermis. Here, we report seven cases of post-renal transplant subcutaneous phaeohyphomycosis, all of which manifested within 1 year after transplantation and were unresponsive to prolonged courses of itraconazole. This is the first case series, to our knowledge, of phaeohyphomycosis in transplant recipients in India. METHOD: We performed a retrospective review of cases of phaeohyphomycosis among kidney transplant recipients for type of transplant, immunosuppression, histopathology, and treatment, with prospective follow-up of healed lesion. RESULTS: An overall incidence of 8.3% was noted, with a median duration of approximately 6 months post transplant to the onset of skin lesion. None of the lesions responded to itraconazole alone and 6/7 lesions were surgically excised. Histopathology showed various lesions and culture could isolate Neocytalidium and Exophiala jeanselmi in two cases. CONCLUSION: Dematiaceous fungi are increasingly implicated in cutaneous lesions in transplant recipients. Histopathology and surgical excision are the appropriate tools for diagnosis and treatment, respectively. PMID- 28994176 TI - Dimethylamine as a Substrate in Hydroaminoalkylation Reactions. AB - Transition-metal-catalyzed hydroaminoalkylations of alkenes have made great progress over the last decade and are heading to become a viable alternative to the industrial synthesis of amines through hydroformylation of alkenes and subsequent reductive amination. In the past, one major obstacle of this progress has been an inability to apply these reactions to the most important amines, methylamine and dimethylamine. Herein, we report the first successful use of dimethylamine in catalytic hydroaminoalkylations of alkenes with good yields. We also report applicability for a variety of alkenes to show the tolerance of the reaction towards different functional groups. Additionally, we present a catalytic dihydroaminoalkylation reaction using dimethylamine, which has never been reported before. PMID- 28994178 TI - Review of appendicectomies over a decade in a tertiary hospital in New Zealand. AB - BACKGROUND: Acute appendicectomy is the most common emergency operation for patients with abdominal pain. In the last decade, computed tomography (CT) scans have increasingly been used to aid in the diagnosis in order to reduce the negative appendicectomy rate. The aim of this study was to evaluate our institution's negative appendicectomy rate and the use of pre-operative imaging. METHODS: A retrospective review was undertaken for all adult patients (>16 years), who underwent an appendicectomy on emergency basis in the years 2004, 2009 and 2014. Cases were identified from the hospital electronic theatre record system. Data were also obtained from the patients records and laboratory reports. RESULTS: A total of 874 patients were included, 227 in 2004, 308 in 2009 and 339 in 2014. The negative appendicectomy rate was 29.1% in 2004, 20.1% in 2009 and 19.5% in 2014 (P = 0.014). Negative appendicectomies were more common in women (P = <0.001), patients between the ages of 16-30 years (P = <0.001) and were associated with low inflammatory markers (median white cell count of 10.2, C reactive protein of 8, P = <0.001). The use of CT scan prior to operation increased between 2009 and 2014 (34 (11.0%) versus 64 (18.9%), P = <0.001). CONCLUSION: Though the number of appendicectomies being performed in our institution has increased over the last decade, the negative appendicectomy rate remains fairly static and the increased use of CT scans did not further decrease the proportion of negative appendicectomies between 2009 and 2014. PMID- 28994177 TI - Sirtuins at the crossroads of stemness, aging, and cancer. AB - Sirtuins are stress-responsive proteins that direct various post-translational modifications (PTMs) and as a result, are considered to be master regulators of several cellular processes. They are known to both extend lifespan and regulate spontaneous tumor development. As both aging and cancer are associated with altered stem cell function, the possibility that the involvement of sirtuins in these events is mediated by their roles in stem cells is worthy of investigation. Research to date suggests that the individual sirtuin family members can differentially regulate embryonic, hematopoietic as well as other adult stem cells in a tissue- and cell type-specific context. Sirtuin-driven regulation of both cell differentiation and signaling pathways previously involved in stem cell maintenance has been described where downstream effectors involved determine the biological outcome. Similarly, diverse roles have been reported in cancer stem cells (CSCs), depending on the tissue of origin. This review highlights the current knowledge which places sirtuins at the intersection of stem cells, aging, and cancer. By outlining the plethora of stem cell-related roles for individual sirtuins in various contexts, our purpose was to provide an indication of their significance in relation to cancer and aging, as well as to generate a clearer picture of their therapeutic potential. Finally, we propose future directions which will contribute to the better understanding of sirtuins, thereby further unraveling the full repertoire of sirtuin functions in both normal stem cells and CSCs. PMID- 28994179 TI - Lysosome-Targeting Amplifiers of Reactive Oxygen Species as Anticancer Prodrugs. AB - Cancer cells produce elevated levels of reactive oxygen species, which has been used to design cancer specific prodrugs. Their activation relies on at least a bimolecular process, in which a prodrug reacts with ROS. However, at low micromolar concentrations of the prodrugs and ROS, the activation is usually inefficient. Herein, we propose and validate a potentially general approach for solving this intrinsic problem of ROS-dependent prodrugs. In particular, known prodrug 4-(N-ferrocenyl-N-benzylaminocarbonyloxymethyl)phenylboronic acid pinacol ester was converted into its lysosome-specific analogue. Since lysosomes contain a higher concentration of active ROS than the cytoplasm, activation of the prodrug was facilitated with respect to the parent compound. Moreover, it was found to exhibit high anticancer activity in a variety of cancer cell lines (IC50 =3.5-7.2 MUm) and in vivo (40 mg kg-1 , NK/Ly murine model) but remained weakly toxic towards non-malignant cells (IC50 =15-30 MUm). PMID- 28994180 TI - A Conjugate of an Anti-Epidermal Growth Factor Receptor (EGFR) VHH and a Cell Penetrating Peptide Drives Receptor Internalization and Blocks EGFR Activation. AB - Overexpression of (mutated) receptor tyrosine kinases is a characteristic of many aggressive tumors, and induction of receptor uptake has long been recognized as a therapeutic modality. A conjugate of a synthetically produced cell-penetrating peptide (CPP), corresponding to amino acids 38-59 of human lactoferrin, and the recombinant llama single-domain antibody (VHH) 7D12, which binds the human epidermal growth factor receptor (EGFR), was generated by sortase A mediated transpeptidation. The conjugate blocks EGF-mediated EGFR activation with higher efficacy than that of both modalities alone; a phenomenon that is caused by both effective receptor blockade and internalization. Thus, the VHH-CPP conjugate shows a combination of activities that implement a highly powerful new design principle to block receptor activation by its clearance from the cell surface. PMID- 28994181 TI - Age-associated dysregulation of protein metabolism in the mammalian oocyte. AB - Reproductive aging is characterized by a marked decline in oocyte quality that contributes to infertility, miscarriages, and birth defects. This decline is multifactorial, and the underlying mechanisms are under active investigation. Here, we performed RNA-Seq on individual growing follicles from reproductively young and old mice to identify age-dependent functions in oocytes. This unbiased approach revealed genes involved in cellular processes known to change with age, including mitochondrial function and meiotic chromosome segregation, but also uncovered previously unappreciated categories of genes related to proteostasis and organelles required for protein metabolism. We further validated our RNA-Seq data by comparing nucleolar structure and function in oocytes from reproductively young and old mice, as this organelle is central for protein production. We examined key nucleolar markers, including upstream binding transcription factor (UBTF), an RNA polymerase I cofactor, and fibrillarin, an rRNA methyltransferase. In oocytes from mice of advanced reproductive age, UBTF was primarily expressed in giant fibrillar centers (GFCs), structures associated with high levels of rDNA transcription, and fibrillarin expression was increased ~2-fold. At the ultrastructural level, oocyte nucleoli from reproductively old mice had correspondingly more prominent fibrillar centers and dense fibrillar centers relative to young controls and more ribosomes were found in the cytoplasm. Taken together, our findings are significant because the growing oocyte is one of the most translationally active cells in the body and must accumulate high-quality maternally derived proteins to support subsequent embryo development. Thus, perturbations in protein metabolism are likely to have a profound impact on gamete health. PMID- 28994182 TI - Traffic congestion and blood pressure elevation: A comparative cross-sectional study in Lebanon. AB - This comparative cross-sectional study examines the association between traffic congestion and elevation of systolic and/or diastolic blood pressure levels among a convenience sample of 310 drivers. Data collection took place during a gas station pause at a fixed time of day. Higher average systolic (142 vs 123 mm Hg) and diastolic (87 vs 78 mm Hg) blood pressures were detected among drivers exposed to traffic congestion compared with those who were not exposed (P<.001), while controlling for body mass index, age, sex, pack-year smoking, driving hours per week, and occupational driving. Moreover, among persons exposed to traffic congestion, longer exposure time was associated with higher systolic and diastolic blood pressures. Further studies are needed to better understand the mechanisms of the significant association between elevated blood pressure and traffic congestion. PMID- 28994183 TI - Angiotensin-converting enzyme inhibitor-induced angioedema: A review of the literature. AB - According to the National Health and Nutrition Examination Survey 2012, one third of antihypertensive prescriptions in the United States in the past decade were for angiotensin-converting enzyme inhibitors (ACEIs). An important and serious side effect of ACEIs is angioedema caused by a reduction in bradykinin degradation. In a national medical chart abstraction study conducted at the US Veterans Affairs Health Care System in 2008, 0.20% of ACEI initiators developed angioedema while on the medication. The angiotensin-converting enzyme is a part of the renin-angiotensin system that converts angiotensin I to angiotensin II. It is additionally responsible for the degradation of bradykinin, which is generated from high molecular weight kininogen by kallikrein. Via bradykinin 2 receptors, bradykinin affects vascular permeability and stimulates the release of substance P, which is a peptide that causes vasodilation and fluid extravasation into tissues. Inhibition of the angiotensin-converting enzyme and subsequent blockade of bradykinin degradation is thought to be a likely explanation for ACEI-induced angioedema. Studies have shown that blacks, women, and smokers are at an increased risk for ACEI-induced angioedema. A 2005 study identified black race, history of drug rash, age older than 65 years, and seasonal allergies as independent risk factors for angioedema related to enalapril. Angioedema may occur at any time during treatment with ACEIs and may continue after the medication is discontinued. The degree of ACEI-angiotensin receptor blocker angioedema cross-reactivity is difficult to determine from the literature. However, multiple studies have reported relatively low rates of native angioedema with angiotensin receptor blockers (approximately half that of ACEIs, or 0.1%) and a low incidence of cross-reactivity (<10%). Common treatments for angioedema, such as antihistamines and glucocorticoids, have not been shown to be effective in ACEI-induced angioedema. However, medications that have been used for acute treatment of hereditary angioedema and target the factors that cause ACEI mediated angioedema are being explored. PMID- 28994184 TI - Racemization at the Asp 58 residue in alphaA-crystallin from the lens of high myopic cataract patients. AB - Post-translational modifications in lens proteins are key causal factors in cataract. As the most abundant post-translational modification in the lens, racemization may be closely related to the pathogenesis of cataract. Racemization of alphaA-crystallin, a crucial structural and heat shock protein in the human lens, could significantly influence its structure and function. In previous studies, elevated racemization from l-Asp 58 to d-isoAsp58 in alphaA-crystallin has been found in age-related cataract (ARC) lenses compared to normal aged human lenses. However, the role of racemization in high myopic cataract (HMC), which is characterized by an early onset of nuclear cataract, remains unknown. In the current study, apparently different from ARC, significantly increased racemization from l-Asp 58 to d-Asp 58 in alphaA-crystallin was identified in HMC lenses. The average racemization rates for each Asp isoform were calculated in ARC and HMC group. In ARC patients, the conversion of l-Asp 58 to d-isoAsp 58, up to 31.89%, accounted for the main proportion in racemization, which was in accordance with the previous studies. However, in HMC lenses, the conversion of l Asp 58 to d-Asp 58, as high as 35.44%, accounted for the largest proportion of racemization in alphaA-crystallin. The different trend in the conversion of alphaA-crystallin by racemization, especially the elevated level of d-Asp 58 in HMC lenses, might prompt early cataractogenesis and a possible explanation of distinct phenotypes of cataract in HMC. PMID- 28994185 TI - Electrostatic-Assisted Liquefaction of Porous Carbons. AB - Porous liquids are a newly developed porous material that combine unique fluidity with permanent porosity, which exhibit promising functionalities for a variety of applications. However, the apparent incompatibility between fluidity and permanent porosity makes the stabilization of porous nanoparticle with still empty pores in the dense liquid phase a significant challenging. Herein, by exploiting the electrostatic interaction between carbon networks and polymerized ionic liquids, we demonstrate that carbon-based porous nanoarchitectures can be well stabilized in liquids to afford permanent porosity, and thus opens up a new approach to prepare porous carbon liquids. Furthermore, we hope this facile synthesis strategy can be widely applicated to fabricate other types of porous liquids, such as those (e.g., carbon nitride, boron nitride, metal-organic frameworks, covalent organic frameworks etc.) also having the electrostatic interaction with polymerized ionic liquids, evidently advancing the development and understanding of porous liquids. PMID- 28994186 TI - Chronic kidney disease with comorbid cardiac dysfunction exacerbates cardiac and renal damage. AB - To address the pathophysiological mechanisms underlying chronic kidney disease with comorbid cardiac dysfunction, we investigated renal and cardiac, functional and structural damage when myocardial infarction (MI) was applied in the setting of kidney injury (induced by 5/6 nephrectomy-STNx). STNx or Sham surgery was induced in male Sprague-Dawley rats with MI or Sham surgery performed 4 weeks later. Rats were maintained for a further 8 weeks. Rats (n = 36) were randomized into four groups: Sham+Sham, Sham+MI, STNx+Sham and STNx+MI. Increased renal tubulointerstitial fibrosis (P < 0.01) and kidney injury molecule-1 expression (P < 0.01) was observed in STNx+MI compared to STNx+Sham animals, while there were no further reductions in renal function. Heart weight was increased in STNx+MI compared to STNx+Sham or Sham+MI animals (P < 0.05), despite no difference in blood pressure. STNx+MI rats demonstrated greater cardiomyocyte cross-sectional area and increased cardiac interstitial fibrosis compared to either STNx+Sham (P < 0.01) or Sham+MI (P < 0.01) animals which was accompanied by an increase in diastolic dysfunction. These changes were associated with increases in ANP, cTGF and collagen I gene expression and phospho-p38 MAPK and phospho-p44/42 MAPK protein expression in the left ventricle. Addition of MI accelerated STNx-induced structural damage but failed to significantly exacerbate renal dysfunction. These findings highlight the bidirectional response in this model known to occur in cardiorenal syndrome (CRS) and provide a useful model for examining potential therapies for CRS. PMID- 28994187 TI - Performance of F-18 FDG PET/CT for predicting malignant potential of gastrointestinal stromal tumors: A systematic review and meta-analysis. AB - BACKGROUND AND AIM: We aimed to explore the role of the diagnostic accuracy of F 18 fluorodeoxyglucose positron emission tomography (F-18 FDG PET) or positron emission tomography/computed tomography (PET/CT) for prediction of malignant potential of gastrointestinal stromal tumor (GIST) through a systematic review and meta-analysis. METHODS: The MEDLINE, Embase, and Cochrane Library database, from the earliest available date of indexing through May 31, 2017, were searched for studies evaluating the diagnostic performance of F-18 FDG PET or PET/CT for prediction of malignant potential of GIST. We determined the sensitivities and specificities across studies, calculated positive and negative likelihood ratios (LR+ and LR-), and constructed summary receiver operating characteristic curves. RESULTS: Across seven studies (188 patients), the pooled sensitivity for F-18 FDG PET or PET/CT was 0.88 (95% confidence interval [CI]: 0.80-0.94) without heterogeneity (chi2 = 6.15, P = 0.72) and a pooled specificity of 0.88 (95% CI: 0.75-0.94) with heterogeneity (chi2 = 23.2, P = 0.01). LR syntheses gave an overall LR+ of 7.2 (95% CI: 3.3-15.3) and LR- of 0.13 (95% CI: 0.07-0.24). The pooled diagnostic odds ratio was 54 (95% CI: 16-181). CONCLUSION: F-18 FDG PET or PET/CT demonstrated good sensitivity and specificity for the prediction of malignant potential of GIST. At present, the literature regarding the use of F-18 FDG PET or PET/CT for the prediction of malignant potential of GIST remains still limited; thus, further large multicenter studies would be necessary to substantiate the diagnostic accuracy of F-18 FDG PET or PET/CT prediction of malignant potential of GIST. PMID- 28994188 TI - Natural history of endoscopically detected hiatus herniae at late follow-up. AB - BACKGROUND: Hiatus herniae are commonly seen at endoscopy. Many patients with a large hiatus hernia are endoscoped for symptoms associated with the hernia and many of these will progress to surgical treatment. However, little is known about the natural history of small to medium size hiatus herniae, and their risk of progressing to a larger hernia requiring surgery. This study aims to determine the need for subsequent surgery in these patients. METHODS: A retrospective audit of the endoscopy database at Flinders Medical Centre and the Repatriation General Hospital in Adelaide, South Australia for the 2-year period 2002-2003 was performed to identify all patients with a hiatus hernia. Patients under the age of 65 and with a sliding hiatus hernia <5 cm in length were selected for this study, and sent a questionnaire which determines the long-term (>10 years) outcome of these herniae. RESULTS: Small- to medium-sized hiatus herniae (<5 cm length) were found at 10% of endoscopies performed. In this group, 38% had reflux as the indication for endoscopy. 1.5% subsequently progressed to anti-reflux surgery or hiatus hernia repair. Thirty-nine percent reported being on proton pump inhibitors for symptom control. No patients required emergency surgical repair of their hiatus hernia. CONCLUSION: While patients with small- to medium sized sliding hiatus hernia commonly have symptomatic reflux, an acute problem requiring emergency surgery is unlikely over long-term follow-up. PMID- 28994189 TI - Assembly, Thermodynamics, and Structure of a Two-Wheeled Composite of a Dumbbell Shaped Molecule and Cylindrical Molecules with Different Edges. AB - A carbonaceous dumbbell was able to spontaneously glue two tubular receptors to form a unique two-wheeled composite through van der Waals interactions, thus forcing the wheel components into contact with each other at the edges. In the present study, two tubular receptors with enantiomeric carbon networks were assembled on the dumbbell joint, and the handedness of the receptors was discriminated, thus leading to the self-sorting of homomeric receptors from a mixture of enantiomeric tubes. The crystal structures of the composites revealed the structural origins of the molecular recognition driven by van der Waals forces as well as the presence of a columnar array of C120 molecules in a 1:1 composite. PMID- 28994190 TI - Analysis of Molecular Orientation in Organic Semiconducting Thin Films Using Static Dynamic Nuclear Polarization Enhanced Solid-State NMR Spectroscopy. AB - Molecular orientation in amorphous organic semiconducting thin-film devices is an important issue affecting device performance. However, to date it has not been possible to analyze the "distribution" of the orientations. Although solid-state NMR (ssNMR) spectroscopy can provide information on the "distribution" of molecular orientations, the technique is limited because of the small amount of sample in the device and the low sensitivity of ssNMR. Here, we report the first application of dynamic nuclear polarization enhanced ssNMR (DNP-ssNMR) spectroscopy for the orientational analysis of amorphous phenyldi(pyren-1 yl)phosphine oxide (POPy2 ). The 31 P DNP-ssNMR spectra exhibited a sufficient signal-to-noise ratio to quantify the distribution of molecular orientations in amorphous films: the P=O axis of the vacuum-deposited and drop-cast POPy2 shows anisotropic and isotropic distribution, respectively. The different molecular orientations reflect the molecular origin of the different charge transport behaviors. PMID- 28994191 TI - Transient Behavior of the Metal Interface in Lithium Metal-Garnet Batteries. AB - The interface between solid electrolytes and Li metal is a primary issue for solid-state batteries. Introducing a metal interlayer to conformally coat solid electrolytes can improve the interface wettability of Li metal and reduce the interfacial resistance, but the mechanism of the metal interlayer is unknown. In this work, we used magnesium (Mg) as a model to investigate the effect of a metal coating on the interfacial resistance of a solid electrolyte and Li metal anode. The Li-Mg alloy has low overpotential, leading to a lower interfacial resistance. Our motivation is to understand how the metal interlayer behaves at the interface to promote increased Li-metal wettability of the solid electrolyte surface and reduce interfacial resistance. Surprisingly, we found that the metal coating dissolved in the molten piece of Li and diffused into the bulk Li metal, leading to a small and stable interfacial resistance between the garnet solid electrolyte and the Li metal. We also found that the interfacial resistance did not change with increase in the thickness of the metal coating (5, 10, and 100 nm), due to the transient behavior of the metal interface layer. PMID- 28994192 TI - Narrow- and regular-diameter implants in the posterior region of the jaws to support single crowns: A 3-year split-mouth randomized clinical trial. AB - OBJECTIVES: The objective of this 3-year split-mouth randomized controlled clinical study was to compare narrow-diameter implants (NDIs) to regular-diameter implants (RDIs) in the posterior region of the jaws (premolars and molars) in regards to (i) the marginal bone level (MBL) and (ii) implant and prosthesis survival and success rates. MATERIAL AND METHODS: A total of 22 patients were included in the study. Each patient received at least one implant of each diameter (O3.3 and O4.1 mm), placed either in the maxilla or mandible to support single crowns. A total 44 implants (22 NDIs and 22 RDIs) were placed and included in the study. Twenty-one implants were placed in the premolar, whereas 23 were placed in molar areas. Radiographic evaluations to access the MBL were performed immediately after implant placement, 1 and 3 years after implant loading. Peri implant clinical variables including probing pocket depth (PPD) and bleeding on probing (BoP) were obtained after crown delivery, 1 and 3 years after loading. Furthermore, the survival and success rates of the implants and prosthesis were also evaluated. RESULTS: Twenty patients were able to complete the study. There was no statistically significant difference regarding MBL between groups at implant placement (p = .084), 1-year (p = .794) and 3-year (p = .598) time intervals. The mean peri-implant bone loss at 3-year follow-up was -0.58 +/- 0.39 mm (95% CI: -0.751 to -0.409) and -0.53 +/- 0.46 mm (95% CI: -0.731 to -0.329) for NDIs and RDIs, respectively. BoP was present at 15% and 10% of NDIs and RDIs, respectively, at 3-year follow-up. PPD >5 mm was observed in 5% and 0% of the implants of NDIs and RDIs, respectively, at 3-year follow-up. At the 3-year examination, the implant success rates were in the NDIs and RDIs sites, respectively, 95% and 100%. The corresponding values for prosthesis success rates were 90% for NDIs and 95% for RDIs. CONCLUSION: The present study demonstrated that NDIs placed to support single crowns in the posterior region did not differ to RDIs in regards to MBL, implant survival, and success rates. PMID- 28994193 TI - Interplay between FGFR2b-induced autophagy and phagocytosis: role of PLCgamma mediated signalling. AB - Signalling of the epithelial splicing variant of the fibroblast growth factor receptor 2 (FGFR2b) induces both autophagy and phagocytosis in human keratinocytes. Here, we investigated, in the cell model of HaCaT keratinocytes, whether the two processes might be related and the possible involvement of PLCgamma signalling. Using fluorescence and electron microscopy, we demonstrated that the FGFR2b-induced phagocytosis and autophagy involve converging autophagosomal and phagosomal compartments. Moreover, the forced expression of FGFR2b signalling mutants and the use of specific inhibitors of FGFR2b substrates showed that the receptor-triggered autophagy requires PLCgamma signalling, which in turn activates JNK1 via PKCdelta. Finally, we found that in primary human keratinocytes derived from light or dark pigmented skin and expressing different levels of FGFR2b, the rate of phagocytosis and autophagy and the convergence of the two intracellular pathways are dependent on the level of receptor expression, suggesting that FGFR2b signalling would control in vivo the number of melanosomes in keratinocytes, determining skin pigmentation. PMID- 28994194 TI - Positive experiences related to living with tinnitus: A cross-sectional survey. AB - OBJECTIVE: The aim of this study was to gain insights related to positive experiences reported by adults with tinnitus living in the United Kingdom. DESIGN: A cross-sectional survey design was used in a sample of adults with tinnitus who were interested in undertaking an Internet-based intervention for tinnitus. SETTING: The study was UK wide and data collection was online. PARTICIPANTS: Participants consisted of 240 adults (137 males, 103 females), with an average age of 48.16 years and average tinnitus duration of 11.52 years (SD: 11.88). MAIN OUTCOME MEASURES: Tinnitus severity was measured by means of the Tinnitus Functional Index. To evaluate the secondary effects of tinnitus, the Insomnia Severity Index, the Hearing Handicap Inventory for Adults-Screening Version and the Cognitive Failures Questionnaires were administered. Positive experiences related to tinnitus were explored using an open-ended question format. RESULTS: Around a third of participants (32.5%) reported positive experiences associated with tinnitus. The number of positive responses ranged from one to eight responses per participant, although there were fewer participants with more than one positive response. The predominant themes concerned for (i) coping; (ii) personal development; (iii) support, and to a lesser extent (iv) outlook. Younger participants, those with a lower hearing disability and those with fewer cognitive failures were more likely to report positive experiences associated with having tinnitus. CONCLUSIONS: This study has identified that personal development and a positive outlook are possible despite experiencing tinnitus. Ways to facilitate positive experiences related to tinnitus should be promoted, as these may reduce the negative consequences associated with tinnitus. The most prevalent positive theme was the ability to cope with tinnitus. Positive experiences were also drawn from having clinical and other support networks. This highlights the importance of providing tinnitus interventions that can assist people in coping with tinnitus, particularly to those less likely to relate tinnitus to any positive experiences. Those most likely to be helped include those who are older with greater cognitive difficulties and a greater hearing disability. PMID- 28994195 TI - Appropriateness, diagnostic value, and outcomes of repeat testing following index echocardiography. AB - AIMS: Emergency admission to hospital is associated with an economic burden and mortality. Echocardiography is often the first-line cardiovascular imaging investigation. Repeat testing is common; however, there are sparse data on the prevalence, appropriateness, or outcome of repeat testing. METHODS: We performed an electronic database search for patients with emergency admissions to our institution in February 2015. An electronic patient record review of inpatient echocardiograms was undertaken. Indications for echocardiography were classified as appropriate, may be appropriate, or rarely appropriate. One-year follow-up for repeat testing and mortality was investigated. RESULTS: A total of 409 of 2306 (17.7%) unplanned/emergency admissions underwent inpatient echocardiography. Abnormalities were identified in 165/409 (40.3%) of these patients; 154 of 409 (37.7%) had a repeat echocardiogram within the next year. Rarely appropriate indications for echocardiography occurred in 51 (33%) of repeat vs 53 (16%) of index echocardiograms, P < .0001. Repeat testing was associated with a change in findings in 17/154 (11%) patients overall. All of whom had an abnormal index echocardiogram and had an appropriate indication. There was no difference in mean survival time between patients who underwent repeat and those who only underwent a single index echocardiogram (310 days vs 327 days), P = .34. CONCLUSION: Inpatient echocardiography in emergency hospital admissions identifies clinically important pathology. Repeated testing is common within 1 year of hospital admission. New diagnostic findings occurred in 11% of patients and only in patients with appropriate studies and an abnormal index echocardiogram. Identification of methods to reduce repeat testing and implement appropriateness criteria is warranted. PMID- 28994196 TI - Demographics, management and treatment outcomes of benign and malignant retroperitoneal tumors in Japan. AB - OBJECTIVES: To show the demographics, type of treatment and clinical outcomes of patients with retroperitoneal tumors in Japan. METHODS: We carried out a retrospective analysis of patients with retroperitoneal tumors treated between 2000 and 2012 at 12 university hospitals in Japan. Histology was re-evaluated using the 2013 World Health Organization classification. RESULTS: A total of 167 patients were included in the analysis. The number of diagnosed patients increased over the 12-year study period. Liposarcoma and schwannoma were the most common histological types among intermediate/malignant and benign tumors, respectively. The intermediate/malignant tumors were larger and were more frequently found in older people. Surgical resection was the primary treatment for 151 patients. The median survival duration for patients with malignant tumors was 91 months, and was significantly shorter than that for patients with benign and intermediate tumors (P < 0.01). R2 resection was associated with significantly shorter survival than R0/R1 resection for malignant tumors (P < 0.01), but not for intermediate. Grossly complete resection of the recurrent tumors improved survival. CONCLUSION: The number of patients diagnosed with retroperitoneal tumors increased over time. R2 resection of primary tumors was found to be associated with poor prognosis in malignant tumors, but not in intermediate tumors. Complete surgical resection of recurrent tumors was associated with a better oncological outcome. PMID- 28994197 TI - In Vino Veritas: An Invitation for Ambitious, Collaborative Proteogenomics Campaigns on Plant and Animal Models. AB - Vitis vinifera has been an emblematic plant for humans since the Neolithic period. Human civilization has been shaped by its domestication as both its medicinal and nutritional values were exploited. It is now cultivated on all habitable continents, and more than 5000 varieties have been developed. A global passion for the art of wine fuels innovation and a profound desire for knowledge on this plant. The genome sequence of a homozygotic cultivar and several RNA-seq datasets on other varieties have been released paving the way to gaining further insight into its biology and tailoring improvements to varieties. However, its genome annotation remains unpolished. In this issue of Proteomics, Chapman and Bellgard (Proteomics 2017, 17, 1700197) discuss how proteogenomics can help improve genome annotation. By mining shotgun proteomics data, they defined new protein-coding genes, refined gene structures, and corrected numerous mRNA splicing events. This stimulating study shows how large international consortia could work together to improve plant and animal genome annotation on a large scale. To achieve this aim, time should be invested to generate comprehensive, high-quality experimental datasets for a wide range of well-defined lineages and exploit them with pipelines capable of handling giant datasets. PMID- 28994198 TI - The incidence of thyroid cartilage invasion in early-stage laryngeal carcinoma: Our experience on sixty-two patients. PMID- 28994200 TI - A nonpharmacological approach to improve sleep quality in older adults. AB - OBJECTIVES: Poor sleep quality is highly prevalent among older adults and is associated with poor quality of life, cognitive and physical decline, depression, and increased mortality. Medication options commonly used are not ideal, and alternative treatment strategies are needed. We evaluate a community-based psychosocial intervention program and its effect on sleep quality in older adults. METHOD: Elderly participants aged 60 and above were included. Those with Geriatric Depression Scale and Geriatric Anxiety Inventory scores above 5 and 10, respectively, were excluded. The community program included tai chi exercise, art therapy, mindfulness awareness practice, and music reminiscence therapy. Pittsburgh Sleep Quality Index, Geriatric Depression Scale, and Geriatric Anxiety Inventory were administered at baseline and at 1 year. RESULTS: A hundred and eighty-nine subjects (44 men, 145 women; mean age = 69 years, SD = 5.7, range = 60-89) participated. The proportion of participants with good sleep quality had increased from 58.2% to 64.6%. Sleep disturbance was significantly reduced (baseline, 1.04; postintervention, 0.76; mean difference 0.28; P < .01); men experienced greater improvement (P < .001). Improvements were independent of changes in depressive and anxiety symptoms. CONCLUSION: Participation in this community program led to positive effects on sleep disturbances after a year. Psychosocial interventions have potential as a nondrug intervention approach for sleep problems, and further research is needed to understand its mediating mechanisms. PMID- 28994199 TI - Inhibition of MEK/ERK signalling pathway promotes erythroid differentiation and reduces HSCs engraftment in ex vivo expanded haematopoietic stem cells. AB - The MEK/ERK pathway is found to be important in regulating different biological processes such as proliferation, differentiation and survival in a wide variety of cells. However, its role in self-renewal of haematopoietic stem cells is controversial and remains to be clarified. The aim of this study was to understand the role of MEK/ERK pathway in ex vivo expansion of mononuclear cells (MNCs) and purified CD34+ cells, both derived from human umbilical cord blood (hUCB). Based on our results, culturing the cells in the presence of an inhibitor of MEK/ERK pathway-PD0325901 (PD)-significantly reduces the expansion of CD34+ and CD34+ CD38- cells, while there is no change in the expression of stemness related genes (HOXB4, BMI1). Moreover, in vivo analysis demonstrates that PD reduces engraftment capacity of ex vivo expanded CD34+ cells. Notably, when ERK pathway is blocked in UCB-MNCs, spontaneous erythroid differentiation is promoted, found in concomitant with increasing number of burst-forming unit erythroid colony (BFU-E) as well as enhancement of erythroid glycophorin-A marker. These results are in total conformity with up-regulation of some erythroid enhancer genes (TAL1, GATA2, LMO2) and down-regulation of some erythroid repressor genes (JUN, PU1) as well. Taken together, our results support the idea that MEK/ERK pathway has a critical role in achieving the correct balance between self-renewal and differentiation of UCB cells. Also, we suggest that inhibition of ERK signalling could likely be a new key for erythroid induction of UCB-haematopoietic progenitor cells. PMID- 28994201 TI - Polyhedral-Like NiMn-Layered Double Hydroxide/Porous Carbon as Electrode for Enhanced Electrochemical Performance Supercapacitors. AB - Polyhedral-like NiMn-layered double hydroxide/porous carbon (NiMn-LDH/PC-x) composites are successfully synthesized by hydrothermal method (x = 1, 2 means different mass percent of porous carbon (PC) in composites). The NiMn-LDH/PC-1 composites possess specific capacitance 1634 F g-1 at a current density of 1 A g 1 , and it is much better than that of pure LDH (1095 F g-1 at 1 A g-1 ). Besides, the sample can retain 84.58% of original capacitance after 3000 cycles at 15 A g-1 . An asymmetric supercapacitor with NiMn-LDH/PC-1 as anode and activated carbon as cathode is fabricated, and the supercapacitor can achieve an energy density of 18.60 Wh kg-1 at a power density of 225.03 W kg-1 . The enhanced electrochemical performance attributes to the high faradaic pseudocapacitance of NiMn-LDH, the introduction of PC, and the 3D porous structure of LDH/PC-1 composites. The introduction of PC hinders serious agglomeration of LDH and further accelerates ions transport. The encouraging results indicate that these materials are one of the most potential candidates for energy storage devices. PMID- 28994202 TI - 'Beak Technique' for emergency dilation of tracheostomy stenosis- a technical note. PMID- 28994203 TI - Highly Spin-Frustrated Magnetism in the Topochemically Prepared Triangular Lattice Cluster Magnets Na3 A2 (MoO4 )2 Mo3 O8 (A=In, Sc). AB - The physical properties of novel cluster-based triangular lattice antiferromagnets Na3 A2 (MoO4 )2 Mo3 O8 (A=In, Sc), synthesized through a topochemical Na-intercalation to nonmagnetic Na2 A2 (MoO4 )2 Mo3 O8 , are reported. The S=1/2 [Mo3 ]11+ clusters form a regular triangular lattice, which gives the magnetic system a strong geometrical spin frustration effect. Despite the strong antiferromagnetic couplings among [Mo3 ]11+ clusters, they show no long-range magnetic orderings down to 0.5 K with the finite residual magnetic entropy. The ground states of Na3 A2 (MoO4 )2 Mo3 O8 have been characterized as a quantum spin liquid, owing to the strong spin frustration of cluster spins on the triangular lattice. PMID- 28994204 TI - Directed evolution of DGAT1 to increase triacylglycerol content. PMID- 28994205 TI - Proteomics and Network Analyses Reveal Inhibition of Akt-mTOR Signaling in CD4+ T Cells by Mycobacterium tuberculosis Mannose-Capped Lipoarabinomannan. AB - Mycobacterium tuberculosis (Mtb) cell wall glycolipid mannose-capped lipoarabinomannan (ManLAM) inhibits CD4+ T-cell activation by inhibiting proximal T-cell receptor (TCR) signaling when activated by anti-CD3. To understand the impact of ManLAM on CD4+ T-cell function when both the TCR-CD3 complex and major costimulator CD28 are engaged, we performed label-free quantitative MS and network analysis. Mixed-effect model analysis of peptide intensity identified 149 unique peptides representing 131 proteins that were differentially regulated by ManLAM in anti-CD3- and anti-CD28-activated CD4+ T cells. Crosstalker, a novel network analysis tool identified dysregulated translation, TCA cycle, and RNA metabolism network modules. PCNA, Akt, mTOR, and UBC were found to be bridge node proteins connecting these modules of dysregulated proteins. Altered PCNA expression and cell cycle analysis showed arrest at the G2M phase. Western blot confirmed that ManLAM inhibited Akt and mTOR phosphorylation, and decreased expression of deubiquitinating enzymes Usp9x and Otub1. Decreased NF-kappaB phosphorylation suggested interference with CD28 signaling through inhibition of the Usp9x-Akt-mTOR pathway. Thus, ManLAM induced global changes in the CD4+ T cell proteome by affecting Akt-mTOR signaling, resulting in broad functional impairment of CD4+ T-cell activation beyond inhibition of proximal TCR-CD3 signaling. PMID- 28994206 TI - The computed tomographic "tree-in-bud" pattern: Characterization and comparison with radiographic and clinical findings in 36 cats. AB - In humans, a CT "tree-in-bud" pattern has been described as a characteristic of centrilobular bronchiolar dilation, with bronchiolar plugging by mucus, pus, or fluid. Aims of this retrospective, descriptive, multi-center study were to characterize the CT appearance of a "tree-in-bud" pattern in a group of cats, and compare this pattern with radiographic and clinical findings. Databases from four hospitals were searched during the period of January 2012 to September 2015 and cats with thoracic radiographs, thoracic CT scans and CT reports describing findings consistent with a "tree-in-bud" pattern were included. Images were reviewed by two veterinary radiologists and characteristics were recorded based on consensus. Clinical findings were recorded by one observer from each center. Thirty-six cats met inclusion criteria. Six cats were asymptomatic, 12 were diagnosed with bronchial disease and 23 were suspected to have bronchial disease. Right cranial and right caudal lung lobes were most commonly affected on both imaging modalities. Localization of the "tree-in-bud" pattern was most often peripheral. On radiographs, the CT "tree-in-bud" pattern often appeared as soft tissue opacity nodules; their number and affected pulmonary segments were often underestimated compared with CT. In conclusion, the "tree-in-bud" pattern should be considered as a differential diagnosis for radiographic soft tissue opaque nodules in feline lungs. Based on lesion localization and presence or suspicion of a concomitant bronchial disease for cats in this sample, authors propose that the CT "tree-in-bud" pattern described in humans is also a characteristic of bronchial or bronchiolar plugging and bronchial disease in cats. PMID- 28994208 TI - The fine print behind the big picture. PMID- 28994207 TI - Identification of peptide-binding sites within BSA using rapid, laser-induced covalent cross-linking combined with high-performance mass spectrometry. AB - We are developing a rapid, time-resolved method using laser-activated cross linking to capture protein-peptide interactions as a means to interrogate the interaction of serum proteins as delivery systems for peptides and other molecules. A model system was established to investigate the interactions between bovine serum albumin (BSA) and 2 peptides, the tridecapeptide budding-yeast mating pheromone (alpha-factor) and the decapeptide human gonadotropin-releasing hormone (GnRH). Cross-linking of alpha-factor, using a biotinylated, photoactivatable p-benzoyl-L-phenylalanine (Bpa)-modified analog, was energy dependent and achieved within seconds of laser irradiation. Protein blotting with an avidin probe was used to detect biotinylated species in the BSA-peptide complex. The cross-linked complex was trypsinized and then interrogated with nano LC-MS/MS to identify the peptide cross-links. Cross-linking was greatly facilitated by Bpa in the peptide, but some cross-linking occurred at higher laser powers and high concentrations of a non-Bpa-modified alpha-factor. This was supported by experiments using GnRH, a peptide with sequence homology to alpha factor, which was likewise found to be cross-linked to BSA by laser irradiation. Analysis of peptides in the mass spectra showed that the binding site for both alpha-factor and GnRH was in the BSA pocket defined previously as the site for fatty acid binding. This model system validates the use of laser-activation to facilitate cross-linking of Bpa-containing molecules to proteins. The rapid cross linking procedure and high performance of MS/MS to identify cross-links provides a method to interrogate protein-peptide interactions in a living cell in a time resolved manner. PMID- 28994209 TI - Identifying patterns of adaptation in breast cancer patients with cancer-related fatigue using response shift analyses at subgroup level. AB - Fatigue is the most prevalent symptom in breast cancer. It might be perceived differently among patients over time as a consequence of the differing patients' adaptation and psychological adjustment to their cancer experience which can be related to response shift (RS). RS analyses can provide important insights on patients' adaptation to cancer but it is usually assumed that RS occurs in the same way in all individuals which is unrealistic. This study aimed to identify patients' subgroups in which different RS effects on self-reported fatigue could occur over time using a combination of methods for manifest and latent variables. The FATSEIN study comprised 466 breast cancer patients followed over a 2-year period. Fatigue was measured with the Multidimensional Fatigue Inventory questionnaire (MFI-20) during 10 visits. A novel combination of Mixed Models, Growth Mixture Modeling, and Structural Equation Modeling was used to assess the occurrence of RS in fatigue changes to identify subgroups displaying different RS patterns over time. An increase in fatigue was evidenced over the 8-month follow up, followed by a decrease between the 8- and 24-month. Four latent classes of patients were identified. Different RS patterns were detected in all latent classes between the inclusion and 8 months (last cycle of chemotherapy). No RS was evidenced between 8- and 24-month. Several RS effects were evidenced in different groups of patients. Women seemed to adapt differently to their treatment and breast cancer experience possibly indicating differing needs for medical/psychological support. PMID- 28994210 TI - Immunomagnetic beads-based isolation of erythropoietins from urine and blood for sports anti-doping control. AB - According to the World Anti-Doping Agency (WADA) technical document for erythropoiesis stimulating agents (ESA) analysis (TD2014EPO), double-blotting of serum/plasma samples is mandatory for all analysis by isoelectric focusing (IEF) and for the confirmation procedures (CP) performed by SDS-PAGE or SAR-PAGE. The goal is to prevent potential cross-reactions of the secondary antibody with remaining proteins in the purified samples. To this end, we have developed an immunopurification method of ESA in serum/plasma samples using a combination of streptavidin-coated immunomagnetic beads and biotinylated anti-EPO polyclonal antibodies. Here we report that this immunomagnetic bead-based purification allows the analysis of serum/plasma samples by single-blotting. Serum and plasma samples, either intact or spiked with different ESAs, were immunopurified and analyzed by single-blotting, after SAR-PAGE or IEF using a cross-reaction minimized secondary antibody coupled to HRP. The results show that when samples are immunopurified according to this strategy, there is no non-specific binding when single-blotting is performed after SAR-PAGE. With IEF, we observe a faint smearing, however, in the pH gradient outside the ESA detection region. These interferences did not alter ESA profiles of spiked urinary samples or of samples received for routine testing. This approach was compared to the MAIIA monoliths purification or to the isolation of ESAs with other combinations of immunomagnetic reagents (ie, anti-Mouse IgG-coated magnetic beads and anti-EPO mAb). The recovery of ESAs was shown to be significant for serum/plasma samples. Our results suggest that single-blotting could be performed on serum/plasma samples without non-specific interferences. Copyright (c) 2017 John Wiley & Sons, Ltd. PMID- 28994211 TI - Sleep duration is associated with sperm chromatin integrity among young men in Chongqing, China. AB - This study explores whether sleep duration is associated with sperm chromatin integrity. To do so, we conducted a three-phase panel study of 796 male volunteers from colleges in Chongqing (China) from 2013 to 2015. Sleep duration was measured using a modified Munich Chronotype Questionnaire. Sperm DNA integrity was examined via Sperm Chromatin Structure Assay and Comet assay. Setting 7-7.5 h day-1 of sleep duration as a reference, either longer or shorter sleep duration was associated negatively with high DNA stainability (HDS) (P = 0.009), which reflected the immaturity of sperm chromatin. The volunteers with > 9.0 h day-1 sleep and those with <= 6.5 h day-1 sleep had 40.7 and 30.3% lower HDS than did volunteers with 7-7.5 h day-1 sleep. No association was found between sleep duration and DNA fragmentation index or Comet assay parameters. This study suggests that sleep duration is associated with sperm chromatin integrity. Further studies are required to validate these findings and investigate the mechanism underlying this association. PMID- 28994213 TI - A novel and innovative hair test to determine glucocorticoid levels in racing camels for use in assessment of doping, health, and disease. AB - The aim of this project was to develop and validate a new test for the analysis of glucocorticoids in camel hair and to use the new test to analyse hair samples from a variety of camel breeds in sports and racing applications. These findings could be of importance when evaluating racing camels for suspected doping offenses or for injury and disease control. Camel hair samples were collected from 30 non-racing dromedary camels along with 3 racing camels in Al Ain, UAE and were decontaminated, pulverised, sonicated, and extracted prior to analysis. A liquid chromatographic-mass spectrometric method was employed to determine the levels of glucocorticoids in the hair samples. The 4 drugs of interest, namely hydrocortisone, dexamethasone, flumethasone and methylprednisolone, and an internal standard were quantified in camel hair samples. All 4 of the glucocorticoids were detected in camel hair samples with concentrations ranging between 31 and 935 pg/mg for hydrocortisone, 8-59 pg/mg for dexamethasone, 0.7 1034 pg/mg for flumethasone and 5-66 pg/mg for methylprednisolone in non-racing camels. One of the racing camels displayed high concentrations of hydrocortisone (1130 pg/mg), flumethasone (2576 pg/mg), methylprednisone (1156 pg/mg) and dexamethasone (29 pg/mg). The authors believe this is the first report of a test for corticosteroids in camel hair. The new test has been validated according to Food and Drug Administration (FDA) guidelines. This new hair test could be useful for further studies in doping control, toxicological studies, pharmacological studies and other clinical applications in camel health, injury, and disease. PMID- 28994214 TI - Effect of replacing alfalfa hay with a mixture of cassava foliage silage and sweet potato vine silage on ruminal and intestinal digestion in sheep. AB - This study aimed to investigate the effects of replacing alfalfa hay (AH) with a mixture of cassava foliage silage and sweet potato vine silage (CSP) (1:1 on a dry matter (DM) basis) on ruminal and intestinal nutrient digestion in sheep. Four wethers were fed a control diet containing 35% of AH and two treatment diets containing 15% and 30% of the CSP as substitute for AH at 1.5 times the metabolizable energy required for maintenance. Replacing AH with the CSP silage did not affect DM intake, whereas it linearly increased (P < 0.05) the intake of ether extract and acid detergent insoluble nitrogen (ADIN). Increasing the CSP substitution linearly decreased (P < 0.05) ruminal DM and neutral detergent fiber (aNDFom) digestibility; however, it did not affect total tract aNDFom digestibility. The CSP substitution did not affect nitrogen (N) intake and duodenal total N flow, whereas it linearly increased duodenal ADIN flow (P < 0.01) and decreased ruminal ammonia-N concentration (P < 0.01), and intestinal (P = 0.08) and total N digestibility (P < 0.01). These results indicate that replacing AH with the CSP reduced the ruminal N degradation as well as the digestion of ruminal aNDFom and intestinal N. PMID- 28994212 TI - High frequency of brain metastases after adjuvant therapy for high-risk melanoma. AB - The incidence of CNS progression in patients with high-risk regional melanoma (stages IIIAN2a-IIIC) is not well characterized. Data from the S0008 trial provided an opportunity to examine the role of CNS progression in treatment failure and survival. All patients were surgically staged. Following wide excision and full regional lymphadenectomy, patients were randomized to receive adjuvant biochemotherapy (BCT) or high-dose interferon alfa-2B (HDI). CNS progression was retrospectively identified from data forms. Survival was measured from date of CNS progression. A total of 402 eligible patients were included in the analysis (BCT: 199, HDI: 203). Median follow-up (if alive) was over 7 years (range: 1 month to 11 years). The site of initial progression was identifiable in 80% of relapsing patients. CNS progression was a component of systemic melanoma relapse in 59/402 patients (15% overall). In 34/402 patients (9%) CNS progression represented the initial site of treatment failure. CNS progression was a component of initial progression in 27% of all patients whose melanoma relapsed (59/221). The risk of CNS progression was highest within 3 years of randomization. The difference in CNS progression rates between treatment arms was not significant (BCT = 25, HDI = 34, P = 0.24). Lymph node macrometastases strongly associated with CNS progression (P = 0.001), while ulceration and head and neck primaries were not significant predictors. This retrospective analysis of the S0008 trial identified a high brain metastasis rate (15%) in regionally advanced melanoma patients. Further studies are needed to establish whether screening plus earlier treatment would improve survival following CNS progression. PMID- 28994215 TI - Psychometric Properties of the Chinese Version of the Eating Attitudes Test in Young Female Patients with Eating Disorders in Mainland China. AB - The study aimed to investigate the reliability and validity of the Chinese version of the eating attitudes test (EAT-26) among female adolescents and young adults in Mainland China. This scale was administered to 396 female eating disorder patients and 406 noneating disorder healthy controls, in addition 35 healthy controls completed a retest after a 4-week intervals. Tests for reliability, convergent validity and receiver operating characteristic analysis were performed to detect the psychometric properties. The EAT-26 demonstrated good internal consistency (Cronbach's alpha = 0.822-0.922), test-retest reliability (interclass correlation coefficient = 0.817) and convergent validity(r = 0.450-0.750). The receiver operating characteristic analysis showed that the cut-off 14 for anorexia nervosa and 15 for bulimia nervosa represented good compromises with approximate sensitivity (0.66-0.68) and specificity (0.85 0.86). Our findings provided evidence that the Chinese version of the EAT-26 was a psychometrically reliable and valid self-rating instrument for identifying people suffering from an eating disorder in Mainland China. A clinical cut-off range between 14 and 15 could be used, but caution should be exercised because of the low sensitivity of the tool. Copyright (c) 2017 John Wiley & Sons, Ltd and Eating Disorders Association. PMID- 28994218 TI - Author Responsibilities. PMID- 28994217 TI - Individually Prefabricated Prosthesis for Maxilla Reconstruction. AB - The reconstruction of maxillofacial bone defects by the intraoperative modeling of implants may reduce the predictability of the esthetic result, leading to more invasive surgery and increased surgical time. To improve the maxillofacial surgery outcome, modern manufacturing methods such as rapid prototyping (RP) technology and methods based on reverse engineering (RE) and medical imaging data are applicable to the manufacture of custom-made maxillary prostheses. After acquisition of data, an individual computer-based 3D model of the bony defect is generated. These data are transferred into RE software to create the prosthesis using a computer-aided design (CAD) model, which is directed into the RP machine for the production of the physical model. The precise fit of the prosthesis is evaluated using the prosthesis and skull models. The prosthesis is then directly used in investment casting such as "Quick Cast" pattern to produce the titanium model. In the clinical reports presented here, reconstructions of two patients with large maxillary bone defects were performed using this new method. The custom prostheses perfectly fit the defects during the operations, and surgery time was reduced. These cases show that the prefabrication of a prosthesis using modern manufacturing technology is an effective method for maxillofacial defect reconstruction. PMID- 28994219 TI - Recognizing Our Reviewers. PMID- 28994220 TI - Bacteremia after supragingival scaling and dental extraction: Culture and molecular analyses. AB - OBJECTIVE: To study the incidence and magnitude of bacteremia after dental extraction and supragingival scaling. SUBJECTS AND METHODS: Blood samples were taken before and 5 and 30 min after dental extraction and supragingival scaling from individuals at high (n = 44) or negligible risk (n = 51) for infective endocarditis. The former received prophylactic antibiotic therapy. Samples were subjected to aerobic and anaerobic culture and quantitative real-time polymerase chain reaction to determine the incidence of bacteremia and total bacterial levels. RESULTS: Patients who did not receive prophylactic antibiotic therapy had a higher incidence of positive blood cultures (30% 5 min after extraction) than patients who received prophylactic antibiotic therapy (0% 5 min after extraction; p < .01). Molecular analysis did not reveal significant differences in the incidence or magnitude of bacteremia between the two patient groups either 5 or 30 min after each of the procedures evaluated. Extraction was associated with higher incidence of bacteremia than supragingival scaling by blood culture (p = .03) and molecular analysis (p = .05). CONCLUSIONS: Molecular methods revealed that dental extraction and supragingival scaling were associated with similar incidence of bacteremia in groups receiving or not prophylactic antibiotic therapy. However, blood culture revealed that antibiotic therapy reduced viable cultivable bacteria in the bloodstream in the extraction group. PMID- 28994221 TI - Direct Production of (R)-3-Hydroxybutyric Acid of High Optical Purity by Halomonas sp. OITC1261 Under Aerobic conditions. AB - The chiral compound (R)-3-hydroxybutyric acid (R-3HB) has some important physiological functions in the human body and can also be applied as a functional material for industrial products. A novel Halomonas sp. OITC1261 isolated from a coastal sediment is selected for efficient production of R-3HB. This strain secreted R-3HB of high optical purity into the extracellular medium while maintaining poly(3-hydroxybutyric acid) (PHB) inside the microbial cell under aerobic conditions. There is a possibility that R-3HB is generated independently of PHB. Under aerobic cultivation, 58 g L-1 (0.65 g L-1 h-1 ) of R-3HB was produced simultaneously with 27 g L-1 (0.30 g L-1 h-1 ) of PHB. This direct production method of R-3HB contributes to the improvement of mass production technology. PMID- 28994222 TI - Guianolactones A and B, Two Rearranged Pentacyclic Limonoids from the Seeds of Carapa guianensis. AB - Two novel rearranged limonoids, guianolactones A (1) and B (2), were isolated from Carapa guianensis Aubl. (Meliaceae) seeds. The structures of 1 and 2 with their absolute configurations were elucidated in detailed examinations using single-crystal X-ray diffraction analyses and 2D NMR spectra. Guianolactone A (1) has a novel 5/6/6/6/6 pentacyclic core including two delta-lactone and a tetrahydropyran ring, while guianolactone B (2) is a novel limonoid with a 6/6/5/6/6 pentacyclic core featuring a delta-lactone and a tetrahydrofuran ring. PMID- 28994223 TI - Multiple Taf subunits of TFIID interact with Ino2 activation domains and contribute to expression of genes required for yeast phospholipid biosynthesis. AB - Expression of phospholipid biosynthetic genes in yeast requires activator protein Ino2 which can bind to the UAS element inositol/choline-responsive element (ICRE) and trigger activation of target genes, using two separate transcriptional activation domains, TAD1 and TAD2. However, it is still unknown which cofactors mediate activation by TADs of Ino2. Here, we show that multiple subunits of basal transcription factor TFIID (TBP-associated factors Taf1, Taf4, Taf6, Taf10 and Taf12) are able to interact in vitro with activation domains of Ino2. Interaction was no longer observed with activation-defective variants of TAD1. We were able to identify two nonoverlapping regions in the N-terminus of Taf1 (aa 1-100 and aa 182-250) each of which could interact with TAD1 of Ino2 as well as with TAD4 of activator Adr1. Specific missense mutations within Taf1 domain aa 182-250 affecting basic and hydrophobic residues prevented interaction with wild-type TAD1 and caused reduced expression of INO1. Using chromatin immunoprecipitation we demonstrated Ino2-dependent recruitment of Taf1 and Taf6 to ICRE-containing promoters INO1 and CHO2. Transcriptional derepression of INO1 was no longer possible with temperature-sensitive taf1 and taf6 mutants cultivated under nonpermissive conditions. This result supports the hypothesis of Taf-dependent expression of structural genes activated by Ino2. PMID- 28994224 TI - Rare and unusual presentation of Cladophialophora infection in a pulmonary transplant cystic fibrosis patient. AB - A 35-year-old woman with severe cystic fibrosis was admitted for sudden loss of strength in both legs, revealing a myelitis. The medullary lesion biopsy revealed phaeohyphomycosis caused by Cladophialophora species. Myelitis caused by Cladophialophora bantiana is a rare disease associated with high mortality. PMID- 28994225 TI - Scaffold Composition Determines the Angiogenic Outcome of Cell-Based Vascular Endothelial Growth Factor Expression by Modulating Its Microenvironmental Distribution. AB - Delivery of genetically modified cells overexpressing Vascular Endothelial Growth Factor (VEGF) is a promising approach to induce therapeutic angiogenesis in ischemic tissues. The effect of the protein is strictly modulated by its interaction with the components of the extracellular matrix. Its therapeutic potential depends on a sustained but controlled release at the microenvironmental level in order to avoid the formation of abnormal blood vessels. In this study, it is hypothesized that the composition of the scaffold plays a key role in modulating the binding, hence the therapeutic effect, of the VEGF released by 3D cell constructs. It is found that collagen sponges, which poorly bind VEGF, prevent the formation of localized hot spots of excessive concentration, therefore, precluding the development of aberrant angiogenesis despite uncontrolled expression by a genetically engineered population of adipose tissue derived stromal cells. On the contrary, after seeding on VEGF-binding egg-white scaffolds, the same cell population caused aberrantly enlarged vascular structures after 14 d. Collagen-based engineered tissues also induced a safe and efficient angiogenesis in both the patch itself and the underlying myocardium in rat models. These findings open new perspectives on the control and the delivery of proangiogenic stimuli, and are fundamental for the vascularization of engineered tissues/organs. PMID- 28994226 TI - Proteinuria in pediatric renal transplant recipients. AB - Proteinuria has been shown to be an important and potentially treatable risk factor for graft loss. The aim of this study was to evaluate prevalence, etiology, and outcome of proteinuria during the follow-up of children with renal transplantation. We retrospectively reviewed the files of renal transplanted children between 2006 and 2016 in our center. All patients were interpreted with respect to the demographic data and clinical and laboratory features including information about proteinuria. Chi-square test and Mann-Whitney U test were used for analysis. Fifty-two children were eligible for the study. Proteinuria was observed in 34 (65%) and nephrotic range proteinuria was detected in 5 (9.6%) patients. Etiology of proteinuria could be identified in 21 patients. Acute rejection and uncontrolled hypertension were the most frequent causes of proteinuria. Proteinuria had resolved during the follow-up in 59% of the patients. We found that children with and without proteinuria had similar glomerular filtration rate at the end of 50 months of follow-up period. Proteinuria seems to be a common complication in renal transplant recipients. Graft functions can be preserved by immediate evaluation of increasing proteinuria, and by fixing treatable causes rapidly and efficiently during the follow-up in majority of the patients. PMID- 28994228 TI - Lithium Azide as an Electrolyte Additive for All-Solid-State Lithium-Sulfur Batteries. AB - Of the various beyond-lithium-ion battery technologies, lithium-sulfur (Li-S) batteries have an appealing theoretical energy density and are being intensely investigated as next-generation rechargeable lithium-metal batteries. However, the stability of the lithium-metal (Li degrees ) anode is among the most urgent challenges that need to be addressed to ensure the long-term stability of Li-S batteries. Herein, we report lithium azide (LiN3 ) as a novel electrolyte additive for all-solid-state Li-S batteries (ASSLSBs). It results in the formation of a thin, compact and highly conductive passivation layer on the Li degrees anode, thereby avoiding dendrite formation, and polysulfide shuttling. It greatly enhances the cycling performance, Coulombic and energy efficiencies of ASSLSBs, outperforming the state-of-the-art additive lithium nitrate (LiNO3 ). PMID- 28994227 TI - Disentangling the mechanisms behind winter snow impact on vegetation activity in northern ecosystems. AB - Although seasonal snow is recognized as an important component in the global climate system, the ability of snow to affect plant production remains an important unknown for assessing climate change impacts on vegetation dynamics at high-latitude ecosystems. Here, we compile data on satellite observation of vegetation greenness and spring onset date, satellite-based soil moisture, passive microwave snow water equivalent (SWE) and climate data to show that winter SWE can significantly influence vegetation greenness during the early growing season (the period between spring onset date and peak photosynthesis timing) over nearly one-fifth of the land surface in the region north of 30 degrees, but the magnitude and sign of correlation exhibits large spatial heterogeneity. We then apply an assembled path model to disentangle the two main processes (via changing early growing-season soil moisture, and via changing the growth period) in controlling the impact of winter SWE on vegetation greenness, and suggest that the "moisture" and "growth period" effect, to a larger extent, result in positive and negative snow-productivity associations, respectively. The magnitude and sign of snow-productivity association is then dependent upon the relative dominance of these two processes, with the "moisture" effect and positive association predominating in Central, western North America and Greater Himalaya, and the "growth period" effect and negative association in Central Europe. We also indicate that current state-of-the-art models in general reproduce satellite-based snow-productivity relationship in the region north of 30 degrees, and do a relatively better job of capturing the "moisture" effect than the "growth period" effect. Our results therefore work towards an improved understanding of winter snow impact on vegetation greenness in northern ecosystems, and provide a mechanistic basis for more realistic terrestrial carbon cycle models that consider the impacts of winter snow processes. PMID- 28994229 TI - General and Efficient Intermolecular [2+2] Photodimerization of Chalcones and Cinnamic Acid Derivatives in Solution through Visible-Light Catalysis. AB - [2+2] Photocycloaddition, for example, the dimerization of chalcones and cinnamic acid derivatives, is a unique strategy to construct cyclobutanes, which are building blocks for a variety of biologically active molecules and natural products. However, most attempts at the above [2+2] addition have focused on solid-state, molten-state, or host-guest systems under ultraviolet-light irradiation in order to overcome the competition of facile geometric isomerization of nonrigid olefins. We report a general and simple method to realize the intermolecular [2+2] dimerization reaction of these acyclic olefins to construct cyclobutanes in a highly regio- and diastereoselective manner in solution under visible light, which provides an efficient solution to a long standing problem. PMID- 28994230 TI - Land use of drained peatlands: Greenhouse gas fluxes, plant production, and economics. AB - Drained peatlands are hotspots for greenhouse gas (GHG) emissions, which could be mitigated by rewetting and land use change. We performed an ecological/economic analysis of rewetting drained fertile peatlands in a hemiboreal climate using different land use strategies over 80 years. Vegetation, soil processes, and total GHG emissions were modeled using the CoupModel for four scenarios: (1) business as usual-Norway spruce with average soil water table of -40 cm; (2) willow with groundwater at -20 cm; (3) reed canary grass with groundwater at -10 cm; and (4) a fully rewetted peatland. The predictions were based on previous model calibrations with several high-resolution datasets consisting of water, heat, carbon, and nitrogen cycling. Spruce growth was calibrated by tree-ring data that extended the time period covered. The GHG balance of four scenarios, including vegetation and soil, were 4.7, 7.1, 9.1, and 6.2 Mg CO2 eq ha-1 year-1 , respectively. The total soil emissions (including litter and peat respiration CO2 + N2 O + CH4 ) were 33.1, 19.3, 15.3, and 11.0 Mg CO2 eq ha-1 year-1 , respectively, of which the peat loss contributed 35%, 24%, and 7% of the soil emissions for the three drained scenarios, respectively. No peat was lost for the wet peatland. It was also found that draining increases vegetation growth, but not as drastically as peat respiration does. The cost-benefit analysis (CBA) is sensitive to time frame, discount rate, and carbon price. Our results indicate that the net benefit was greater with a somewhat higher soil water table and when the peatland was vegetated with willow and reed canary grass (Scenarios 2 and 3). We conclude that saving peat and avoiding methane release using fairly wet conditions can significantly reduce GHG emissions, and that this strategy should be considered for land use planning and policy-making. PMID- 28994232 TI - It is time to restore Rules for Authorship of scientific publications. PMID- 28994231 TI - TIPE1 suppresses invasion and migration through down-regulating Wnt/beta-catenin pathway in gastric cancer. AB - Epithelial-mesenchymal transition (EMT) plays an important role in the invasiveness and metastasis of gastric cancer. Therefore, identifying key molecules involved in EMT will provide new therapeutic strategy for treating patients with gastric cancer. TIPE1 is a newly identified member of the TIPE (TNFAIP8) family, and its contributions to progression and metastasis have not been evaluated. In this study, we found that the levels of TIPE1 were significantly reduced and inversely correlated with differentiation status and distant metastasis in primary gastric cancer tissues. We further observed overexpression of TIPE1 in aggressive gastric cancer cell lines decreased their metastatic properties both in vitro and in vivo as demonstrated by markedly inhibiting EMT and metastasis of gastric cancer cells in nude mice. Consistently, gene silencing of TIPE1 in well-differentiated gastric cancer cell line (AGS) inhibited these processes. Mechanistically, we found that TIPE1-medicated Wnt/beta-catenin signalling was one of the critical signal transduction pathways that link TIPE1 to EMT inhibition. Importantly, TIPE1 dramatically restrained the expression and activities of MMP2 and MMP9 which are demonstrated to promote tumour progression and are implicated in EMT. Collectively, these findings provide new evidence for a better understanding of the biological activities of TIPE1 in progression and metastasis of gastric cancer and suggest that TIPE1 may be an innovative diagnostic and therapeutic target of gastric cancer. PMID- 28994233 TI - Large Continuous Mechanical Gradient Formation via Metal-Ligand Interactions. AB - Mechanical gradients are often employed in nature to prevent biological materials from damage by creating a smooth transition from strong to weak that dissipates large forces. Synthetic mimics of these natural structures are highly desired to improve distribution of stresses at interfaces and reduce contact deformation in manmade materials. Current synthetic gradient materials commonly suffer from non continuous transitions, relatively small gradients in mechanical properties, and difficult syntheses. Inspired by the polychaete worm jaw, we report a novel approach to generate stiffness gradients in polymeric materials via incorporation of dynamic monodentate metal-ligand crosslinks. Through spatial control of metal ion content, we created a continuous mechanical gradient that spans over a 200 fold difference in stiffness, approaching the mechanical contrast observed in biological gradient materials. PMID- 28994234 TI - Outcomes of a co-facilitation skills training programme for mental health service users, family members, and clinicians: the EOLAS project. AB - Health policy is increasingly advocating for involvement of service users and family members in service development. In the present study, we evaluated the impact of a 4-day education programme in co-facilitation skills on clinician and peer (service users and family members) knowledge, confidence, and subsequent experience as co-facilitators. The programme was designed to train peers and clinicians as co-facilitators on a clinician and peer-led information programme for people experiencing mental health problems. The study employed a mixed methods design involving a pre-post survey with 128 participants, and follow-up qualitative interviews with a sample of 17 participants. To examine changes in levels of knowledge and confidence in facilitating from time 1 (T1) to time 2 (T2), paired sample t-tests were conducted, and thematic analysis was conducted on the interviews. The programme had a statistically-significant positive impact on participants' knowledge, confidence, and skills, with no significant difference between the facilitator groups (i.e. service user, family member, and clinician) in terms of their improvement at the end of the training, indicating that all groups benefited equally from the training. A majority of participants reported a high level of preparedness as co-facilitators and an open and respectful approach towards each other's expertise, and many continued to gain skills and develop their confidence as they co-facilitated the 8-week EOLAS programme ('eolas' is the Irish word for knowledge). The findings also provide evidence of the acceptability and feasibility of the programme, and appears to be the first detailed study reported on a programme of this nature. PMID- 28994235 TI - Lipo-Protein Emulsion Structure in the Diet Affects Protein Digestion Kinetics, Intestinal Mucosa Parameters and Microbiota Composition. AB - SCOPE: Food structure is a key factor controlling digestion and nutrient absorption. We test the hypothesis that protein emulsion structure in the diet may affect digestive and absorptive processes. METHODS & RESULTS: Rats (n = 40) are fed for 3 weeks with two diets chemically identical but based on lipid protein liquid-fine (LFE) or gelled-coarse (GCE) emulsions that differ at the macro- and microstructure levels. After an overnight fasting, they ingest a 15 N labeled LFE or GCE test meal and are euthanized 0, 15 min, 1 h, and 5 h later. 15 N enrichment in intestinal contents and blood are measured. Gastric emptying, protein digestion kinetics, 15 N absorption, and incorporation in blood protein and urea are faster with LFE than GCE. At 15 min time point, LFE group shows higher increase in GIP portal levels than GCE. Three weeks of dietary adaptation leads to higher expression of cationic amino acid transporters in ileum of LFE compared to GCE. LFE diet raises cecal butyrate and isovalerate proportion relative to GCE, suggesting increased protein fermentation. LFE diet increases fecal Parabacteroides relative abundance but decreases Bifidobacterium, Sutterella, Parasutterella genera, and Clostridium cluster XIV abundance. CONCLUSION: Protein emulsion structure regulates digestion kinetics and gastrointestinal physiology, and could be targeted to improve food health value. PMID- 28994236 TI - mRNA transport in fungal top models. AB - Eukaryotic cells rely on the precise determination of when and where proteins are synthesized. Spatiotemporal expression is supported by localization of mRNAs to specific subcellular sites and their subsequent local translation. This holds true for somatic cells as well as for oocytes and embryos. Most commonly, mRNA localization is achieved by active transport of the molecules along the actin or microtubule cytoskeleton. Key factors are molecular motors, adaptors, and RNA binding proteins that recognize defined sequences or structures in cargo mRNAs. A deep understanding of this process has been gained from research on fungal model systems such as Saccharomyces cerevisiae and Ustilago maydis. Recent highlights of these studies are the following: (1) synergistic binding of two RNA-binding proteins is needed for high affinity recognition; (2) RNA sequences undergo profound structural rearrangements upon recognition; (3) mRNA transport is tightly linked to membrane trafficking; (4) mRNAs and ribosomes are transported on the cytoplasmic surface of endosomes; and (5) heteromeric protein complexes are, most likely, assembled co-translationally during endosomal transport. Thus, the study of simple fungal model organisms provides valuable insights into fundamental mechanisms of mRNA transport boosting the understanding of similar events in higher eukaryotes. WIREs RNA 2018, 9:e1453. doi: 10.1002/wrna.1453 This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein-RNA Recognition RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes RNA Export and Localization > RNA Localization. PMID- 28994237 TI - CO2 Reduction on the Pre-reduced Mixed Ionic-Electronic Conducting Perovskites La0.6 Sr-0.4 FeO3-delta and SrTi0.7 Fe0.3 O3-delta. AB - The activity of the pre-reduced perovskites La0.6 Sr0.4 FeO3-delta (LSF64) and SrTi0.7 Fe0.3 O3-delta (STF73) for the CO2 reduction to CO was investigated with special focus on the reactivity of oxide-dissolved hydrogen. This is of particular interest in hydrogen solid-oxide electrolysis cell (H-SOEC) technology, where proton-conducting ceramics are used and the reaction 2e- +2H+ +CO2 ->CO+H2 O is of central importance. To clarify if hydrogen dissolved in LSF64 and STF73 partakes in the CO2 reduction, temperature-programmed reduction (TPR) in H2 , followed by temperature-programmed reoxidation (TPO) in CO2 and, moreover, temperature-programmed desorption (TPD) of ad- and absorbed species were utilized. The experiments reveal that 50 mol % of the CO2 is converted by hydrogen dissolved in STF73 and reacts quantitatively. On the other hand, LSF64 converts less than 20 mol % of CO2 via dissolved hydrogen and a residual of bulk OH is still detectable after CO2 -TPO. PMID- 28994239 TI - Erratum. PMID- 28994238 TI - Specificity of presenilin-1- and presenilin-2-dependent gamma-secretases towards substrate processing. AB - The two presenilin-1 (PS1) and presenilin-2 (PS2) homologs are the catalytic core of the gamma-secretase complex, which has a major role in cell fate decision and Alzheimer's disease (AD) progression. Understanding the precise contribution of PS1- and PS2-dependent gamma-secretases to the production of beta-amyloid peptide (Abeta) from amyloid precursor protein (APP) remains an important challenge to design molecules efficiently modulating Abeta release without affecting the processing of other gamma-secretase substrates. To that end, we studied PS1- and PS2-dependent substrate processing in murine cells lacking presenilins (PSs) (PS1KO, PS2KO or PS1-PS2 double-KO noted PSdKO) or stably re-expressing human PS1 or PS2 in an endogenous PS-null (PSdKO) background. We characterized the processing of APP and Notch on both endogenous and exogenous substrates, and we investigated the effect of pharmacological inhibitors targeting the PSs activity (DAPT and L-685,458). We found that murine PS1 gamma-secretase plays a predominant role in APP and Notch processing when compared to murine PS2 gamma secretase. The inhibitors blocked more efficiently murine PS2- than murine PS1 dependent processing. Human PSs, especially human PS1, expression in a PS-null background efficiently restored APP and Notch processing. Strikingly, and contrary to the results obtained on murine PSs, pharmacological inhibitors appear to preferentially target human PS1- than human PS2-dependent gamma-secretase activity. PMID- 28994240 TI - Benchmarking Water Oxidation Catalysts Based on Iridium Complexes: Clues and Doubts on the Nature of Active Species. AB - Water oxidation (WO) is a central reaction in the photo- and electro-synthesis of fuels. Iridium complexes have been successfully exploited as water oxidation catalysts (WOCs) with remarkable performances. Herein, we report a systematic study aimed at benchmarking well-known Ir WOCs, when NaIO4 is used to drive the reaction. In particular, the following complexes were studied: cis-[Ir(ppy)2 (H2 O)2 ]OTf (ppy=2-phenylpyridine) (1), [Cp*Ir(H2 O)3 ]NO3 (Cp*=1,2,3,4,5 pentamethyl-cyclopentadienyl anion) (2), [Cp*Ir(bzpy)Cl] (bzpy=2-benzoylpyridine) (3), [Cp*IrCl2 (Me2 -NHC)] (NHC=N-heterocyclic carbene) (4), [Cp*Ir(pyalk)Cl] (pyalk=2-pyridine-isopropanoate) (5), [Cp*Ir(pic)NO3 ] (pic=2-pyridine carboxylate) (6), [Cp*Ir{(P(O)(OH)2 }3 ]Na (7), and mer-[IrCl3 (pic)(HOMe)]K (8). Their reactivity was compared with that of IrCl3 ?n H2 O (9) and [Ir(OH)6 ]2- (10). Most measurements were performed in phosphate buffer (0.2 m), in which 2, 4, 5, 6, 7, and 10 showed very high activity (yield close to 100 %, turnover frequency up to 554 min-1 with 10, the highest ever observed for a WO-driven by NaIO4 ). The found order of activity is: 10>2~4>6>5>7>1>9>3>8. Clues concerning the molecular nature of the active species were obtained, whereas its exact nature remains doubtfully. PMID- 28994241 TI - Legumain correlates with neuroblastoma differentiation and can be used in prodrug design. AB - Neuroblastoma (NB) is a highly malignant solid tumor in children. The cysteine endopeptidase legumain is expressed in adult solid tumors, but its expression in NB has not been examined. In this study, we assayed legumain expression in two NB cell lines and in microarrays of tumor tissues collected from 46 children with undifferentiated NB, differentiated NB, and ganglioneuroblastoma. Correlation analyses showed that legumain was expressed in all NB cell lines tested and that expression correlated with the degree of tumor differentiation. The efficacy, specificity, and toxicity of EMC-AANL-DOX, a novel doxorubicin-based legumain activated prodrug, were then evaluated in mouse model of NB. Compared with DOX, EMC-AANL-DOX showed greater inhibition of tumor growth and a lower toxicity at high doses. Neither leukocyte or platelet counts nor renal function or cardiac anatomy differed significantly between the EMC-AANL-DOX and control groups (p > .05), suggesting that the prodrug caused minimal bone marrow depression and did not induce renal or cardiac damage. The good specificity and efficacy of EMC-AANL DOX and low toxicity recommend its use in the treatment of NB. Correlation analyses of NB differentiation and legumain expression may reveal a novel anti tumor-related functions of the drug and a new strategy for the treatment of pediatric solid tumors. PMID- 28994242 TI - Spring fasting behavior in a marine apex predator provides an index of ecosystem productivity. AB - The effects of declining Arctic sea ice on local ecosystem productivity are not well understood but have been shown to vary inter-specifically, spatially, and temporally. Because marine mammals occupy upper trophic levels in Arctic food webs, they may be useful indicators for understanding variation in ecosystem productivity. Polar bears (Ursus maritimus) are apex predators that primarily consume benthic and pelagic-feeding ice-associated seals. As such, their productivity integrates sea ice conditions and the ecosystem supporting them. Declining sea ice availability has been linked to negative population effects for polar bears but does not fully explain observed population changes. We examined relationships between spring foraging success of polar bears and sea ice conditions, prey productivity, and general patterns of ecosystem productivity in the Beaufort and Chukchi Seas (CSs). Fasting status (>=7 days) was estimated using serum urea and creatinine levels of 1,448 samples collected from 1,177 adult and subadult bears across three subpopulations. Fasting increased in the Beaufort Sea between 1983-1999 and 2000-2016 and was related to an index of ringed seal body condition. This change was concurrent with declines in body condition of polar bears and observed changes in the diet, condition and/or reproduction of four other vertebrate consumers within the food chain. In contrast, fasting declined in CS polar bears between periods and was less common than in the two Beaufort Sea subpopulations consistent with studies demonstrating higher primary productivity and maintenance or improved body condition in polar bears, ringed seals, and bearded seals despite recent sea ice loss in this region. Consistency between regional and temporal variation in spring polar bear fasting and food web productivity suggests that polar bears may be a useful indicator species. Furthermore, our results suggest that spatial and temporal ecological variation is important in affecting upper trophic-level productivity in these marine ecosystems. PMID- 28994243 TI - Addressing weight bias and discrimination: moving beyond raising awareness to creating change. AB - Weight discrimination is the unjust treatment of individuals because of their weight. There have been very few interventions to address weight discrimination, due in part to the lack of consensus on key messages and strategies. The objective of the third Canadian Weight Bias Summit was to review current evidence and move towards consensus on key weight bias and obesity discrimination reduction messages and strategies. Using a modified brokered dialogue approach, participants, including researchers, health professionals, policy makers and people living with obesity, reviewed the evidence and moved towards consensus on key messages and strategies for future interventions. Participants agreed to these key messages: (1) Weight bias and obesity discrimination should not be tolerated in education, health care and public policy sectors; (2) obesity should be recognized and treated as a chronic disease in health care and policy sectors; and (3) in the education sector, weight and health need to be decoupled. Consensus on future strategies included (1) creating resources to support policy makers, (2) using personal narratives from people living with obesity to engage audiences and communicate anti-discrimination messages and (3) developing a better clinical definition for obesity. Messages and strategies should be implemented and evaluated using consistent theoretical frameworks and methodologies. PMID- 28994244 TI - Nitrogen-Doped Carbon Nanotubes Derived from Metal-Organic Frameworks for Potassium-Ion Battery Anodes. AB - To tackle the issue of the poor rate capability of graphite anodes for potassium ion batteries (KIBs), nitrogen-doped carbon nanotubes (NCNTs) with an edge-open layer-alignment structure were synthesized using a simple and scalable approach of pyrolyzing cobalt-containing metal-organic frameworks. The unique structure enables a facile and fast intercalation of K ions. As anodes of KIBs, the NCNTs demonstrated an improved rate capability by a high capacity retention of 102 mA h g-1 at a high current density of 2000 mA g-1 and a good stability without evident capacity loss over 500 cycles at 2000 mA g-1 . Our findings can help to develop highperformance anode materials for potassium-ion batteries as large-scale and low-cost energy-storage systems. PMID- 28994245 TI - Chemoinformatics in France. PMID- 28994246 TI - Time to learn: How chronotype impacts education. AB - A growing body of literature has linked chronotype and sleep to school performance. Chronotype is under the control of the circadian clock and refers to sleep timing and diurnal preferences. Chronotype changes with age and is latest during adolescence, giving rise to a mismatch between the (late) circadian clock and the (early) school clock. In general, evening (late) chronotypes obtain lower grades. School performance is influenced by many other factors, such as motivation, intelligence, and conscientiousness. Some of these factors also relate to chronotype. The present paper reviews the literature on the relationship between chronotype and school performance, with the aim of suggesting hypotheses about the mechanisms behind this complex phenomenon and exploring solutions for an optimized school system. Based on the literature reviewed, we hypothesize that chronotype has both a direct and an indirect effect on school performance. The indirect effect is mediated by factors such as conscientiousness, learning/achieving motivation, mood, and alertness. In addition, time of day of testing plays an important role since the chronotype effect on grades is strongest in the morning and disappears in the afternoon. Strategies to decrease the mismatch between the adolescent circadian clock and the school clock could involve light interventions to advance the students' sleep timing, delays in school starting times, and rearrangements of test schedules (tests later in the day). PMID- 28994247 TI - Transcatheter embolization of a large mediastinal bronchial artery aneurysm with short neck. PMID- 28994248 TI - MALDI Mass Spectrometry Imaging: A Novel Tool for the Identification and Classification of Amyloidosis. AB - Amyloidosis is a group of diseases caused by extracellular accumulation of fibrillar polypeptide aggregates. So far, diagnosis is performed by Congo red staining of tissue sections in combination with polarization microscopy. Subsequent identification of the causative protein by immunohistochemistry harbors some difficulties regarding sensitivity and specificity. Mass spectrometry based approaches have been demonstrated to constitute a reliable method to supplement typing of amyloidosis, but still depend on Congo red staining. In the present study, we used matrix-assisted laser desorption/ionization mass spectrometry imaging coupled with ion mobility separation (MALDI-IMS MSI) to investigate amyloid deposits in formalin-fixed and paraffin-embedded tissue samples. Utilizing a novel peptide filter method, we found a universal peptide signature for amyloidoses. Furthermore, differences in the peptide composition of ALlambda and ATTR amyloid were revealed and used to build a reliable classification model. Integrating the peptide filter in MALDI IMS MSI analysis, we developed a bioinformatics workflow facilitating the identification and classification of amyloidosis in a less time and sample consuming experimental setup. Our findings demonstrate also the feasibility to investigate the amyloid's protein composition, thus paving the way to establish classification models for the diverse types of amyloidoses and to shed further light on the complex process of amyloidogenesis. PMID- 28994250 TI - Synthesis and evaluation of a novel 99m Tc nitrido radiopharmaceutical with alendronate dithiocarbamate as a potential bone-imaging agent. AB - Currently, a popular strategy for designing novel radioprobes as bone-imaging agents is based on the concept of bifunctional radiopharmaceuticals. Considering the dithiocarbamate ligand can act as a suitable bifunctional linking agent to attach technetium-99m (99m Tc) to corresponding target molecules, in this study, alendronate dithiocarbamate (ALNDTC) was synthesized and radiolabeled with [99m Tc=N]2+ core by ligand exchange reaction to produce 99m TcN-ALNDTC complex, for the potential use as a novel probe for bone imaging. The radiochemical purity of the complex was over 90%. The complex was stable in vitro and could bind to hydroxyapatite. The partition coefficient result indicated it was hydrophilic, and an evaluation of biodistribution in mice indicated that the complex exhibited a higher bone uptake than did 99m Tc-labeled methylenediphosphonate (99m Tc-MDP). Further, single photon emission computed tomography imaging study indicated clear accumulation in bone, suggesting that 99m TcN-ALNDTC would be a promising candidate for bone imaging. PMID- 28994251 TI - Painful loss of vision after an episode of herpes simplex encephalitis. PMID- 28994252 TI - Hypokalaemic metabolic alkalosis resembing Gitelman syndrome with focal segmental glomerulosclerosis. PMID- 28994253 TI - Addiction medicine ethics: relapse, no lapse and the struggle to treat addicts like everyone else. AB - Two case studies are presented as a focus for discussion of ethics in addiction medicine. The first is that of the alcohol-dependent patient who receives a liver transplant. The second is that of a heroin-dependent patient who continues to inject himself while in a general medical ward. I make some comments about the obligations of doctors to treat those who cause harm to themselves as they would treat those who are 'not responsible'. PMID- 28994249 TI - Molecular pathways of oestrogen receptors and beta-adrenergic receptors in cardiac cells: Recognition of their similarities, interactions and therapeutic value. AB - Oestrogen receptors (ERs) and beta-adrenergic receptors (betaARs) play important roles in the cardiovascular system. Moreover, these receptors are expressed in cardiac myocytes and vascular tissues. Numerous experimental observations support the hypothesis that similarities and interactions exist between the signalling pathways of ERs (ERalpha, ERbeta and GPR30) and betaARs (beta1 AR, beta2 AR and beta3 AR). The recently discovered oestrogen receptor GPR30 shares structural features with the betaARs, and this forms the basis for the interactions and functional overlap. GPR30 possesses protein kinase A (PKA) phosphorylation sites and PDZ binding motifs and interacts with A-kinase anchoring protein 5 (AKAP5), all of which enable its interaction with the betaAR pathways. The interactions between ERs and betaARs occur downstream of the G-protein-coupled receptor, through the Galphas and Galphai proteins. This review presents an up-to-date description of ERs and betaARs and demonstrates functional synergism and interactions among these receptors in cardiac cells. We explore their signalling cascades and the mechanisms that orchestrate their interactions and propose new perspectives on the signalling patterns for the GPR30 based on its structural resemblance to the betaARs. In addition, we explore the relevance of these interactions to cell physiology, drugs (especially beta-blockers and calcium channel blockers) and cardioprotection. Furthermore, a receptor-independent mechanism for oestrogen and its influence on the expression of betaARs and calcium-handling proteins are discussed. Finally, we highlight promising therapeutic avenues that can be derived from the shared pathways, especially the phosphatidylinositol-3-OH kinase (PI3K/Akt) pathway. PMID- 28994254 TI - HMG CoA reductase inhibitor associated myositis and autoimmune hepatitis. PMID- 28994255 TI - Do all services provided as part of a clinical trial require research ethics and governance review? AB - Appropriate ethical oversight underpins the conduct of all clinical trials in Australia. In addition, clinical trials require a suitable approach to research governance in order to ensure that research is appropriately governed. However, such governance processes are often onerous and time-consuming and are not required when trial practices are more appropriately understood as standard of care clinical services. PMID- 28994256 TI - Pneumococcal vaccination and incident hospitalisation for pneumonia in type 2 diabetes: the Fremantle Diabetes Study Phase II. AB - Pneumococcal polysaccharide vaccine should be given to patients with diabetes at diagnosis with up to two further 5-yearly doses. In 1465 representative community based Fremantle Diabetes Study Phase II participants with type 2 diabetes (mean age 66 years, 52% males), 624 (42.6%) self-reported pneumococcal vaccination in the previous 5 years. Vaccination was significantly associated with insulin treatment and cardiovascular pharmacotherapy, suggesting that medical reviews provide the opportunity to address sub-optimal coverage. PMID- 28994257 TI - 'A most malignant malady': a rare case of laryngeal tuberculosis in epidermal growth factor receptor mutant lung adenocarcinoma. PMID- 28994258 TI - USA withdrawal from Paris climate agreement: requiring unity among physicians worldwide more than ever before? PMID- 28994259 TI - Long distance heart transplantation: a tale of two cities. AB - In this 'paired' case report, we describe two heart transplants performed 3 days apart at our centre. Both cases involved very prolonged transportation time of the donor heart. In one case, the donor heart was transported in an ice chest, while in the other case the organ was transported using a normothermic ex vivo perfusion (NEVP) system. The additional retrieval costs incurred by the use NEVP were more than offset by the reduction in subsequent inpatient costs. PMID- 28994260 TI - Author reply. PMID- 28994261 TI - The purpose of the College. PMID- 28994262 TI - Association between altered QT interval in sepsis and mortality: a possible effect of antimicrobial therapy? PMID- 28994263 TI - Patient safety and the Triple Aim. PMID- 28994264 TI - Recent advances in malignant melanoma. AB - In Australia, there is a high incidence of melanoma, and until recently, the treatment and median overall survival for advanced metastatic melanoma had not changed in decades. The recognition of BRAF as an important tumour oncogene in melanoma has led to the development of targeted therapies, and in the last few years, we have seen the impact of these therapies, with significant improvement in response rate, duration of disease control and overall survival for patients with BRAF mutation-positive metastatic melanoma. Concurrently, the science of immunotherapy has evolved beyond the knowledge of the importance of the immune system in cancer, leading to the development of checkpoint inhibitors. The development of checkpoint inhibitors as a tolerable and effective therapy for metastatic melanoma, which has demonstrated improved response rates, duration of control and overall survival for patients, has implications beyond the care of patients with metastatic melanoma as these therapies are being trialled in other malignancies. This article will review the current standard of care and available therapies for metastatic malignant melanoma. PMID- 28994265 TI - Recognition of giant cell arteritis in patients with polymyalgia rheumatica who have a stroke: a cautionary tale. AB - An 82-year-old woman with polymyalgia rheumatica (PMR) on prednisone 7 mg daily was admitted to an acute stroke unit with a right homonymous hemianopia, a left posterior cerebral artery occlusion and occipital lobe infarct. She had raised inflammatory markers, did not have a temporal artery biopsy, and was discharged on the same dose of prednisone. After 21 months, off prednisone, her ophthalmologist, concerned about giant cell arteritis (GCA), restarted prednisone 40 mg daily, with rapid, profound visual improvement. After 3 days her general practitioner, noting normal baseline inflammatory markers, stopped treatment-with rapid visual reversion. It is critical to recognise GCA in patients with PMR admitted to a stroke unit and not to withdraw prematurely corticosteroids once commenced. PMID- 28994266 TI - Core-shell microspheres with porous nanostructured shells for liquid chromatography. AB - The development of new stationary phases has been the key aspect for fast and efficient high-performance liquid chromatography separation with relatively low backpressure. Core-shell particles, with a solid core and porous shell, have been extensively investigated and commercially manufactured in the last decade. The excellent performance of core-shell particles columns has been recorded for a wide range of analytes, covering small and large molecules, neutral and ionic (acidic and basic), biomolecules and metabolites. In this review, we first introduce the advance and advantages of core-shell particles (or more widely known as superficially porous particles) against non-porous particles and fully porous particles. This is followed by the detailed description of various methods used to fabricate core-shell particles. We then discuss the applications of common silica core-shell particles (mostly commercially manufactured), spheres-on sphere particles and core-shell particles with a non-silica shell. This review concludes with a summary and perspective on the development of stationary phase materials for high-performance liquid chromatography applications. PMID- 28994267 TI - Pupillary light reflex and circadian synchronization in the elderly. AB - Most elderly lack a synchronized circadian rhythm and often cannot benefit from light therapy. Non-visual effects of light are mediated through intrinsic photosensitive retinal ganglion cells (ipRGCs). With chromatic pupillometry, the functionality of ipRGCs and their functional circuit in the brain can be tested. PMID- 28994268 TI - Classification of Lacrimal Punctal Stenosis and Its Related Histopathological Feature in Patients with Epiphora. AB - PURPOSE: To evaluate the classification of punctal stenosis based on the shape of the external punctum, clinical characteristics and histopathologic features. METHODS: Patients who experienced tearing and were diagnosed with punctal stenosis were evaluated in this study. Punctal stenosis was classified according to the shape of the lower external punctum, which included membranous type, slit type, horseshoe type, and pinpoint type. Tear meniscus height, 2% fluorescein dye disappearance test and lacrimal pathway irrigation were measured or performed. For treatment, a punctal snip operation and silicone tube placement were performed, and the peripunctal histopathological findings were evaluated. RESULTS: Punctal stenosis was classified into four types: membranous type (17 eyes, 21.5%), slit type (11 eyes, 13.9%), horseshoe type (25 eyes, 31.6%), and pinpoint type (26 eyes, 32.9%). The tear meniscus was significantly higher, and the 2% fluorescein dye disappeared significantly more slowly in the punctal stenosis group. However, correlation of the tear meniscus height and 2% fluorescein dye disappearance test with the punctum shape was not statistically significant. A history of previous chemotherapy was significantly associated with the occurrence of punctal stenosis, especially the membranous type (p < 0.05). Histopathologic evaluation of the punctum showed differences between the punctum types. Pinpoint puncta exhibited a high density of muscle fibers, while they were faintly visible in the membranous type. CONCLUSIONS: Acquired punctal stenosis has various shapes, and the major types of stenotic puncta exhibited unique histopathologic features. Punctal stenosis and its pathophysiology may be related to multiple factors, such as age and systemic 5-fluorouracil chemotherapy history. PMID- 28994269 TI - Peripapillary Choroidal Thickness Change of Polypoidal Choroidal Vasculopathy after Anti-vascular Endothelial Growth Factor. AB - PURPOSE: To investigate the peripapillary choroidal thickness (PCT) of polypoidal choroidal vasculopathy (PCV) and exudative age-related macular degeneration (AMD) and to evaluate their responses to anti-vascular endothelial growth factor (VEGF). METHODS: Thirty eyes with PCV and 25 eyes with exudative AMD who were treatment naive were included in this study. PCT and subfoveal choroidal thickness were evaluated both before and after intravitreal anti-VEGF. RESULTS: The initial mean PCT of PCV (153.78 +/- 56.23 MUm) was thicker than that of exudative AMD (88.77 +/- 23.11 MUm, p < 0.001). Temporal, superior, nasal, and inferior PCTs of PCV were all thicker than those observedin exudative AMD (all p < 0.05). After anti-VEGF, the mean PCT of PCV was significantly reduced (134.17 +/- 41.66 MUm, p < 0.001), but the same was not true not in exudative AMD (86.87 +/- 22.54 MUm, p = 0.392). PCTshowed a similar tendency in all quadrants. CONCLUSIONS: PCV exhibits a thick choroid in the peripapillary region. PCT decreases after anti-VEGF in PCV but not in exudative AMD. In exudative AMD, subfoveal choroidal thickness decreased, but that in the peripapillary region did not. PMID- 28994270 TI - Bilateral Arteritic Anterior Ischemic Optic Neuropathy Associated with Giant Cell Arteritis in Korea. PMID- 28994271 TI - Imaging evaluation of non-alcoholic fatty liver disease: focused on quantification. AB - Non-alcoholic fatty liver disease (NAFLD) has been an emerging major health problem, and the most common cause of chronic liver disease in Western countries. Traditionally, liver biopsy has been gold standard method for quantification of hepatic steatosis. However, its invasive nature with potential complication as well as measurement variability are major problem. Thus, various imaging studies have been used for evaluation of hepatic steatosis. Ultrasonography provides fairly good accuracy to detect moderate-to-severe degree hepatic steatosis, but limited accuracy for mild steatosis. Operator-dependency and subjective/qualitative nature of examination are another major drawbacks of ultrasonography. Computed tomography can be considered as an unsuitable imaging modality for evaluation of NAFLD due to potential risk of radiation exposure and limited accuracy in detecting mild steatosis. Both magnetic resonance spectroscopy and magnetic resonance imaging using chemical shift technique provide highly accurate and reproducible diagnostic performance for evaluating NAFLD, and therefore, have been used in many clinical trials as a non-invasive reference of standard method. PMID- 28994273 TI - Secretory Carcinoma Arising in a Fibroadenoma: A Brief Case Report. PMID- 28994272 TI - Programmed Death-Ligand 1 Expression and Its Correlation with Lymph Node Metastasis in Papillary Thyroid Carcinoma. AB - BACKGROUND: The immunotherapeutic role of programmed death-ligand 1 (PD-L1) in life expectancy in many cancers has been highlighted. However, data regarding PD L1 expression in papillary thyroid carcinoma (PTC) are limited. In this study, we describe the PD-L1 and programmed cell death protein 1 (PD-1) expressions in PTC and analyze their correlation with lymph node (LN) metastasis. METHODS: Clinicopathological data were obtained from 116 patients with PTC who were treated in Gyeongsang National University Hospital, Jinju, Korea in 2009. Tissue microarray blocks were made using representative paraffin blocks of classical PTCs excluding follicular variants. Two pathologists graded the proportion and intensity of PD-L1 and PD-1 expression in both tumor and inflammatory cells. According to their proportions, positive PTC cells were scored as negative (0%), grade 1 (1%-50%), and grade 2 (51%-100%). Similarly, positive inflammatory cells were graded as negative (0%), grade 1 (1%-10%), and grade 2 (11%-20%). The intensity of each protein expression was simplified as positive or negative. RESULTS: A statistically significant correlation exists between the proportions of PD-1 and PD-L1 expression both in papillary carcinoma (p=.001) and peritumoral lymphoid cells in the thyroid (p<.001). In addition, the proportion of PD-L1 expression in PTC cells was closely related to metastatic LNs (p=.036). CONCLUSIONS: PD-L1 is a valuable predictive marker for LN metastasis in PTC. Immunomodulating therapies that inhibit PD-L1 might be an option for patients with LN metastasis. PMID- 28994274 TI - Thyroid Cytology in India: Contemporary Review and Meta-analysis. AB - Fine-needle aspiration cytology (FNAC) is a screening test for triaging thyroid nodules, aiding in subsequent clinical management. However, the advantages have been overshadowed by the multiplicity of reporting systems and a wide range of nomenclature used. The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) was formulated in 2007, to give the world a uniform thyroid cytology reporting system, facilitating easy interpretation by the clinicians. Here, we review the status of thyroid FNAC in India in terms of various reporting systems used including a meta-analysis of the previously published data. An extensive literature search was performed using internet search engines. The reports with detailed classification system used in thyroid cytology were included. The meta analysis of published data was compared with the implied risk of malignancy by TBSRTC. More than 50 studies were retrieved and evaluated. TBSRTC is currently the most widely used reporting system with different studies showing good efficacy and interobserver concordance. Ancillary techniques have, as of now, limited applicability and acceptability in thyroid cytology in India. Twenty eight published articles met the criteria for inclusion in the meta-analysis. When compared with TBSRTC recommendations, the meta-analysis showed a higher risk of malignancy for categories I and III. Thyroid FNAC is practiced all over India. TBSRTC has found widespread acceptance, with most institutions using this system for routine thyroid cytology reporting. However, reasons for a high malignancy risk for categories I and III need to be looked into. Various possible contributing factors are discussed in the review. PMID- 28994275 TI - Combined Adenosquamous and Large Cell Neuroendocrine Carcinoma of the Gallbladder. AB - Large cell neuroendocrine carcinoma (LCNEC) of the gallbladder is extremely rare and usually combined with other type of malignancy, mostly adenocarcinoma. We report an unusual case of combined adenosquamous carcinoma and LCNEC of the gallbladder in a 54-year-old woman. A radical cholecystectomy specimen revealed a 4.3*4.0 cm polypoid mass in the fundus with infiltration of adjacent liver parenchyma. Microscopically, the tumor consisted of two distinct components. Adenosquamous carcinoma was predominant and abrupt transition from adenocarcinoma to squamous cell carcinoma was observed. LCNEC showed round cells with large, vesicular nuclei, abundant mitotic figures, and occasional pseudorosette formation. The patient received adjuvant chemotherapy. However, multiple liver metastases were identified at 3-month follow-up. Metastatic nodules were composed of LCNEC and squamous cell carcinoma components. Detecting LCNEC component is important in gallbladder cancer, because the tumor may require a different chemotherapy regimen and show early metastasis and poor prognosis. PMID- 28994276 TI - Thyroid Fine-Needle Aspiration Practice in the Philippines. AB - Fine-needle aspiration (FNA) is a well accepted initial approach in the management of thyroid lesions. It has come a long way since its introduction for nearly a century ago. In the Philippines, FNA of the thyroid was first introduced 30 years ago and has been utilized until now as a mainstay in the diagnosis of thyroid malignancy. The procedure is performed by pathologists, endocrinologists, surgeons, and radiologists. Most pathologists report the cytodiagnosis using a combination of the aspiration biopsy cytology method that closely resembles the histopathologic diagnosis of thyroid disorders and the six-tier nomenclature of The Bethesda System for Reporting Thyroid Cytopathology. Local endocrinologists and surgeons follow the guidelines of the 2015 American Thyroid Association in the management of thyroid disorders. There is still a paucity of local research studies but available data deal with cytohistologic correlations, sensitivity, specificity, and accuracy rates as well as usefulness of ultrasound-guided FNA. Cytohistologic correlations have a wide range of sensitivity from 30.7% to 73% and specificity from 83% to 100%. The low sensitivity can be attributed to poor tissue sampling since a majority of the thyroid FNA is done by palpation only. The reliability can be improved if FNA is guided by ultrasound as attested in both international and local studies. Overall, FNA of the thyroid has enabled the diagnosis of thyroid disorders with an accuracy of 72.8% to 87.2% and it correlates well with histopathology. PMID- 28994277 TI - Enhanced Thermoelectric Properties of Ag-Modified Bi0.5Sb1.5Te3 Composites by a Facile Electroless Plating Method. AB - A large-scale and facile electroless plating Ag method has been developed to fabricate high-performing Ag/Bi0.5Sb1.5Te3 (Ag/BST) composites. Ag can be doped into BST and also forms Ag2Te secondary phase in BST, leading to a low lattice thermal conductivity of 0.34 Wm-1K-1. Consequently, a peak zT of 1.07 and average zT of 1.02 are achieved in 0.03wt% Ag/BST. The average zT value is enhanced by 100% in the temperature interval from 300 to 500 K compared with that of Ag-free BST. This work provides a facile and large-scale method to fabricate the high performance Bi2Te3-based alloy for applying in the low-temperature power generation. PMID- 28994278 TI - Electro-Grafted Electrode with Graphene-Oxide-Like DNA Affinity for Ratiometric Homogeneous Electrochemical Biosensing of MicroRNA. AB - This work demonstrated for the first time a simple and rapid approach to endow the electrode with the excellent discrimination ability over single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) through the robust electrochemical grafting of in situ generated 1-naphthalenesulfonate (NS-) diazonium salt onto the surface of indium tin oxide (ITO) electrode. On the basis of understanding the influence of sequence and length on the binding affinity of ssDNA and dsDNA toward NS- grafted ITO (NS--ITO) electrode, these interesting findings were successfully employed to rationally develop a ratiometric homogeneous electrochemical biosensing platform for microRNA based on the affinity-mediated signal transduction. The achievement of ultrasensitive detection of microRNA lies in a compatibly designed T7 exonuclease-assisted isothermal amplification strategy, in which the presence of target microRNA initiated the continual and opposite affinity inversion of two rationally engineered electrochemical signal reporters, methylene blue (MB) labeled hairpin reporter and ferrocene (Fc) labeled dsDNA reporter, toward NS--ITO electrode, thereby providing the ratiometric transduction and amplification of the homogeneous electrochemical output signal. By measuring the distinct variation in the peak current intensity ratios of Fc and MB tags, this ratiometric homogeneous electrochemical microRNA biosensing platform showed a detection limit of 25 aM, which is much lower than that of the reported homogeneous electrochemical biosensors. Therefore, we envision that the proposed approach will find useful applications in disease molecular diagnoses and biomedicine. PMID- 28994279 TI - Pyridine-Based Electron-Transport Materials with High Solubility, Excellent Film Forming Ability, and Wettability for Inkjet-Printed OLEDs. AB - Film morphology has predominant influence on the performance of multilayered organic light-emitting diodes (OLEDs), whereas there is little reported literature from the angle of the molecular level to investigate the impact on film-forming ability and device performance. In this work, four isomeric cross linkable electron-transport materials constructed with pyridine, 1,2,4-triazole, and vinylbenzyl ether groups were developed for inkjet-printed OLEDs. Their lowest unoccupied molecular orbital (~3.20 eV) and highest occupied molecular orbital (~6.50 eV) levels are similar, which are mainly determined by the 1,2,4 triazole groups. The triplet energies of these compounds can be tuned from 2.51 to 2.82 eV by different coupling modes with the core of pyridine, where the 2,6 pyridine-based compound has the highest value of 2.82 eV. Film formation and solubility of the compounds were investigated. It was found that the 2,6-pyridine based compound outperformed the 2,4-pyridine, 2,5-pyridine, and 3,5-pyridine based compounds. The spin-coated blue OLEDs based on the four compounds have achieved over 14.0% external quantum efficiencies (EQEs) at the luminance of 100 cd m-2, and a maximum EQE of 12.1% was obtained for the inkjet-printed device with 2,6-pyridine-based compound. PMID- 28994280 TI - Stable and Biocompatible Mushroom beta-Glucan Modified Gold Nanorods for Cancer Photothermal Therapy. AB - Naturally occurring beta-glucans have been widely regarded as a natural source for functional foods and pharmaceuticals due to their immunomodulatory property and antitumor activity. However, physicochemically stable and biocompatible beta glucans are rarely explored as a carrier for nanomaterials to overcome the problems of aggregation and nanotoxicity. Here, we developed highly stable and biocompatible mushroom beta-glucan coated gold nanorods (AuNR-Glu) for cancer photothermal therapy by integrating Pleurotus tuber-regium sclerotial beta-glucan (Glu) and plasmonic gold nanorods (AuNRs) possessing photothermal property in the second near-infrared (NIR-II) window. AuNR-Glu showed high colloidal stability in various biological media, even in simulated gastric fluid. Moreover, AuNR-Glu had low cytotoxicity and high photothermal stability, which are excellent characteristics for photothermal agents for cancer therapy. In vitro experiments showed that AuNR-Glu nanohybrid was effective against MCF-7 (only 4.5 +/- 0.9% viability) at a low dose of 20 MUg/mL under NIR-II at a safe laser power density (0.75 W/cm2). Natural mushroom beta-glucans are potential functional polymers that can be used to fabricate nanohybrids for biomedical applications. PMID- 28994281 TI - pH and Glucose Dual-Responsive Injectable Hydrogels with Insulin and Fibroblasts as Bioactive Dressings for Diabetic Wound Healing. AB - pH and glucose dual-responsive injectable hydrogels were prepared through the cross-linking of Schiff's base and phenylboronate ester using phenylboronic modified chitosan, poly(vinyl alcohol) and benzaldehyde-capped poly(ethylene glycol). Protein drugs and live cells could be incorporated into the hydrogels during the in situ cross-linking, displaying sustained and pH/glucose-triggered drug release from the hydrogels and cell viability and proliferation in the three dimensional hydrogel matrix as well. Hence, the hydrogels with insulin and fibroblasts were considered as bioactive dressings for diabetic wound healing. A streptozotocin-induced diabetic rat model was used to evaluate the efficacy of hydrogel dressings in wound repair. The results revealed that the incorporation of insulin and L929 in the hydrogels could promote neovascularization and collagen deposition and enhance the wound-healing process of diabetic wounds. Thus, the drug- and cell-loaded hydrogels have promising potential in wound healing as a medicated system for various therapeutic proteins and live cells. PMID- 28994282 TI - Role of Shellfish Aquaculture in the Reduction of Eutrophication in an Urban Estuary. AB - Land-based management has reduced nutrient discharges; however, many coastal waterbodies remain impaired. Oyster "bioextraction" of nutrients and how oyster aquaculture might complement existing management measures in urban estuaries was examined in Long Island Sound, Connecticut. Eutrophication status, nutrient removal, and ecosystem service values were estimated using eutrophication, circulation, local- and ecosystem-scale models, and an avoided-costs valuation. System-scale modeling estimated that 1.31% and 2.68% of incoming nutrients could be removed by current and expanded production, respectively. Up-scaled local scale results were similar to system-scale results, suggesting that this up scaling method could be useful in bodies of water without circulation models. The value of removed nitrogen was estimated using alternative management costs (e.g., wastewater treatment) as representative, showing ecosystem service values of $8.5 and $470 million per year for current and maximum expanded production, respectively. These estimates are conservative; removal by clams in Connecticut, oysters and clams in New York, and denitrification are not included. Optimistically, the calculation of oyster-associated removal from all leases in both states (5% of bottom area) plus denitrification losses showed increases to 10%-30% of annual inputs, which would be higher if clams were included. Results are specific to Long Island Sound, but the approach is transferable to other urban estuaries. PMID- 28994283 TI - Carbon Nanotubes versus Graphene as Flexible Transparent Electrodes in Inverted Perovskite Solar Cells. AB - Transparent carbon electrodes, carbon nanotubes, and graphene were used as the bottom electrode in flexible inverted perovskite solar cells. Their photovoltaic performance and mechanical resilience were compared and analyzed using various techniques. Whereas a conventional inverted perovskite solar cells using indium tin oxide showed a power conversion efficiency of 17.8%, the carbon nanotube- and graphene-based cells showed efficiencies of 12.8% and 14.2%, respectively. An established MoO3 doping was used for carbon electrode-based devices. The difference in the photovoltaic performance between the carbon nanotube- and graphene-based cells was due to the difference in morphology and transmittance. Raman spectroscopy, and cyclic flexural testing revealed that the graphene-based cells were more susceptible to strain than the carbon nanotube-based cells, though the difference was marginal. Overall, despite higher performance, the transfer step for graphene has lower reproducibility. Thus, the development of better graphene transfer methods would help maximize the current capacity of graphene-based cells. PMID- 28994284 TI - Gastro-Resistant Insulin Receptor-Binding Peptide from Momordica charantia Improved the Glucose Tolerance in Streptozotocin-Induced Diabetic Mice via Insulin Receptor Signaling Pathway. AB - Momordica charantia is a commonly used food and has been used for the management of diabetes. Our previous study has identified an insulin receptor (IR)-binding protein (mcIRBP) from Momordica charantia. Here we identified the gastro resistant hypoglycemic bioactive peptides from protease-digested mcIRBP. By in vitro digestion and IR kinase activity assay, we found that a 9-amino-acid residue peptide, mcIRBP-9, was a gastro-resistant peptide that enhanced IR kinase activities. mcIRBP-9 activated IR signaling transduction pathway, which resulted in the phosphorylation of IR, the translocation of glucose transporter 4, and the uptake of glucose in cells. Intraperitoneal and oral administration of mcIRBP-9 stimulated the glucose clearance by 30.91 +/- 0.39% and 32.09 +/- 0.38%, respectively, in streptozotocin-induced diabetic mice. Moreover, a pilot study showed that daily ingestion of mcIRBP-9 for 30 days decreased the fasting blood glucose levels and glycated hemoglobin (HbA1c) levels by 23.62 +/- 6.14% and 24.06 +/- 1.53%, respectively. In conclusion, mcIRBP-9 is a unique gastro resistant bioactive peptide generated after the digestion of mcIRBP. Furthermore, oral administration of mcIRBP-9 improves both the glucose tolerance and the HbA1c levels in diabetic mice via targeting IR signaling transduction pathway. PMID- 28994285 TI - Biologically Inspired Design of Nanoparticle Artificial Antigen-Presenting Cells for Immunomodulation. AB - Particles engineered to engage and interact with cell surface ligands and to modulate cells can be harnessed to explore basic biological questions as well as to devise cellular therapies. Biology has inspired the design of these particles, such as artificial antigen-presenting cells (aAPCs) for use in immunotherapy. While much has been learned about mimicking antigen presenting cell biology, as we decrease the size of aAPCs to the nanometer scale, we need to extend biomimetic design to include considerations of T cell biology-including T-cell receptor (TCR) organization. Here we describe the first quantitative analysis of particle size effect on aAPCs with both Signals 1 and 2 based on T cell biology. We show that aAPCs, larger than 300 nm, activate T cells more efficiently than smaller aAPCs, 50 nm. The 50 nm aAPCs require saturating doses or require artificial magnetic clustering to activate T cells. Increasing ligand density alone on the 50 nm aAPCs did not increase their ability to stimulate CD8+ T cells, confirming the size-dependent phenomenon. These data support the need for multireceptor ligation and activation of T-cell receptor (TCR) nanoclusters of similar sizes to 300 nm aAPCs. Quantitative analysis and modeling of a nanoparticle system provides insight into engineering constraints of aAPCs for T cell immunotherapy applications and offers a case study for other cell-modulating particles. PMID- 28994286 TI - Novel Derivative of Bardoxolone Methyl Improves Safety for the Treatment of Diabetic Nephropathy. AB - Currently, no effective and safe medicines are available to treat diabetic nephropathy (DN). Bardoxolone methyl (CDDO-Me) has displayed promising anti-DN activity as well as serious side effects in clinical trials, probably because the highly reactive alpha-cyano-alpha,beta-unsaturated ketone (CUK) in ring A of CDDO Me can covalently bind to thiol functionalities in many biomacromolecules. In this study, we designed and synthesized a gamma-glutamyl transpeptidase (GGT) based and CUK-modified derivative of CDDO-Me (2) to address this issue. 2 can be specifically cleaved by GGT, which is highly expressed in the kidney, to liberate CDDO-Me in situ. It should be noted that 2 exhibited anti-DN efficacy comparable to that of CDDO-Me with much less toxicity in cells and db/db mice, suggesting that its safety is better than CDDO-Me. Our findings not only reveal the therapeutic potential of 2 but also provide a strategy to optimize other synthetic molecules or natural products bearing a pharmacophore like CUK to achieve safer pharmaceutical drugs. PMID- 28994288 TI - Interfacial Effects in Solid-Liquid Electrolytes for Improved Stability and Performance of Dye-Sensitized Solar Cells. AB - With the purpose of achieving stable dye-sensitized solar cells (DSSCs) with high efficiency, a new type of soft matter electrolyte is tested in which specific amounts of nanosized silica particles are finely dispersed in short-chained polyethylene glycol dimethylether encompassing an iodide/triiodide redox mediator. This results in a solid-liquid composite having synergistic electrical and favorable mechanical properties. The combination of interfacial effects and particle network formation promotes enhanced ion transport, which directly impacts the short-circuit photocurrent density. Thorough analysis reveals that this newly elaborated class of electrolytes is able to improve, at the same time, the thermal and long-term stability of DSSCs, as well as power conversion efficiency under standard and lower irradiation intensities. Lab-scale devices with champion efficiency exceeding 11% under attenuated sunlight (20 mW cm-2, with a compact TiO2 blocking layer) are obtained, along with impressively stable performance under both thermal stress and light soaking in an indoor environment (>96% performance retention after 2500 h of accelerated aging under full sun alternated with thermal ramps), matching the durability criteria applied to silicon solar cells for outdoor applications. The new findings might foster widespread practical application of DSSCs. PMID- 28994287 TI - Independent Generation and Reactivity of Thymidine Radical Cations. AB - Thymidine radical cation (1) is produced by ionizing radiation and has been invoked as an intermediate in electron transfer in DNA. Previous studies on its structure and reactivity have utilized thymidine as a precursor, which limits quantitative product analysis because thymidine is readily reformed from 1. In this investigation, radical cation 1 is independently generated via beta heterolysis of a pyrimidine radical generated photochemically from an aryl sulfide. Thymidine is the major product (33%) from 1 at pH 7.2. Diastereomeric mixtures of thymidine glycol and the corresponding 5-hydroxperoxides resulting from water trapping of 1 are formed. Significantly lower yields of products such as 5-formyl-2'-deoxyuridine that are ascribable to deprotonation from the C5 methyl group of 1 are observed. Independent generation of the N3-methyl analogue of 1 (NMe-1) produces considerably higher yields of products derived from water trapping, and these products are formed in much higher yields than those attributable to the C5-methyl group deprotonation in NMe-1. N3-Methyl-thymidine is, however, the major product and is produced in as high as 70% yield when the radical cation is produced in the presence of excess thiol. The effects of exogenous reagents on product distributions are consistent with the formation of diffusively free radical cations (1, NMe-1). This method should be compatible with producing radical cations at defined positions within DNA. PMID- 28994289 TI - Structural Characterization and Immunostimulatory Activity of Polysaccharides from Brassica rapa L. . AB - Two neutral polysaccharides (BRNP-1, 6.9 kDa; BRNP-2, 4.8 kDa) were purified from the common edible plant Brassica rapa L. via the combined techniques of ion exchange chromatography and high-performance gel permeation chromatography. Monosaccharide composition analysis showed that BRNP-1 and BRNP-2 were composed of glucosyl residues. Methylation and 1D- and 2D-NMR analyses revealed that both BRNP-1 and BRNP-2 contained a backbone chain that was composed of alpha-D-(1 -> 4)-linked Glcp residues and side chains that were composed of terminally linked Glcp residues attached at the O-6 position of backbone-glycosyl residues. BRNP-1 and BRNP-2, however, differed in branch degree and molecular weight. Bioassay results showed that treatment with the higher dosage (400 MUg/mL) of BRNP-1 and BRNP-2 stimulated the proliferation, NO release, and cytokine secretion (IL-6 and TNF-alpha) of RAW264.7 macrophages. These results suggested that BRNP-1 and BRNP 2 may enhance macrophage-mediated immune responses. PMID- 28994290 TI - Coupling Real-Time Time-Dependent Density Functional Theory with Polarizable Force Field. AB - Real-time time-dependent density functional theory (RT-TDDFT) is a powerful tool for obtaining spectroscopic observables and understanding complex, time-dependent properties. Currently, performing RT-TDDFT calculations on large, fully quantum mechanical systems is not computationally feasible. Previously, polarizable mixed quantum mechanical and molecular mechanical (QM/MMPol) models have been successful in providing accurate, yet efficient, approximations to a fully quantum mechanical system. Here we develop a coupling scheme between induced dipole based QM/MMPol and RT-TDDFT. Our approach is validated by comparing calculated spectra with both real-time and linear-response TDDFT calculations. The model developed within provides an accurate method for performing RT-TDDFT calculations on extended systems while accounting for mutual polarization between the quantum mechanical and molecular mechanical regions. PMID- 28994291 TI - Potential Energy Curves, Transition Dipole Moments, and Franck-Condon Factors of the 12 Low-Lying States of BrO- Anion. AB - This work investigates the spectroscopic parameters, vibrational levels, and transition probabilities of 12 low-lying states, which are generated from the first dissociation limit, Br(2Pu) + O-(2Pu), of the BrO- anion. The 12 states are X1Sigma+, 21Sigma+, 11Sigma-, 11Pi, 21Pi, 11Delta, a3Pi, 13Sigma+, 23Sigma+, 13Sigma-, 23Pi, and 13Delta. The potential energy curves are calculated with the complete active-space self-consistent field method, which is followed by the internally contracted multireference configuration interaction approach with Davidson modification. The dissociation energy D0 of X1Sigma+ state is determined to be approximately 26876.44 cm-1, which agrees well with the experimental one of 26494.50 cm-1. Of these 12 states, the 21Sigma+, 11Sigma-, 21Pi, 11Delta, 13Sigma+, 23Sigma+, 23Pi, and 13Delta states are very weakly bound states, whose well depths are only several-hundred cm-1. The a3Pi, 23Pi, and 13Delta states are inverted and account for the spin-orbit coupling effect. No states are repulsive regardless of whether the spin-orbit coupling effect is included. The spectroscopic parameters and vibrational levels are determined. The transition dipole moments of 12-pair electronic states are calculated. Franck-Condon factors of a number of transitions of more than 20-pair electronic states are evaluated. The electronic transitions are discussed. The spin-orbit coupling effect on the spectroscopic parameters and vibrational properties is profound for all the states except for X1Sigma+, a3Pi, and 11Pi. The spectroscopic parameters and transition probabilities obtained in this paper can provide some powerful guidelines for observing these states in a proper spectroscopy experiment, in particular the states that have very shallow potential wells. PMID- 28994292 TI - Modulation of the Photophysical, Photochemical, and Electrochemical Properties of Re(I) Diimine Complexes by Interligand Interactions. AB - The photophysical and photochemical properties of transition metal complexes have attracted considerable attention because of their recent applications as photocatalysts in artificial photosynthesis and organic synthesis, as light emitters in electroluminescent (EL) devices, and as dyes in solar cells. The general control methods cannot be always used to obtain transition metal complexes with photochemical properties that are suitable for the above-mentioned applications. In the fields of solar energy conversion, strong metal-to-ligand charge-transfer (MLCT) absorption of redox photosensitizers and/or photocatalysts in the visible region with long wavelength is essential. However, the usual methods, i.e., introduction of electron-withdrawing groups into the electron accepting ligand and/or weak-field ligands into the central metal, have several drawbacks, including shorter excited-state lifetime, lower emission efficiency, and lower oxidation and reduction power. Herein we describe a new method to control the photophysical, photochemical, and electrochemical properties of Re(I) diimine carbonyl complexes that have been widely used in various fields such as photocatalysts for CO2 reduction and emitters in EL devices and sensors. This method involves the introduction of interligand interactions (pi-pi and CH-pi interactions) into the Re(I) complexes; the aromatic diimine ligand coordinating to the Re center approaches the aryl groups on the phosphine ligand or ligands at the cis position, which "compulsorily" induces a weak interaction between these aromatic groups. As a result of this interligand interaction, the Re complexes with the aromatic diimine ligand and the arylphosphine ligand(s) exhibit red shifted 1MLCT absorption but afford blue-shifted emission from the triplet metal to-ligand charge-transfer (3MLCT) excited state. This increases the oxidation power and lifetime of the 3MLCT excited state. These unique property changes are favorable, particularly for redox photosensitizers. The interligand interaction is strongly expressed by the ring-shaped multinuclear Re(I) complexes (Re-rings). In the case of Re-rings with high steric hindrance due to a small inner cavity, the lifetime of the 3MLCT excited state is up to 8 MUs and the emission quantum yield is up to 70%. These properties cannot be obtained by the corresponding mononuclear Re(I) complexes, which generally exhibit shorter lifetimes (<1 MUs) and lower emission quantum yields (<10%). Some of the Re-rings could be successfully applied as efficient photosensitizers in photocatalytic systems for CO2 reduction; the highest quantum yields for CO2 reduction were achieved by using photocatalytic systems composed of Re-rings as the photosensitizers and Re(I) (82%), Ru(II) (58%), and Mn(I) (48%) complexes as catalysts. This interligand interaction potentially provides unique and useful methods for controlling the photophysical, photochemical, and electrochemical functions of various metal complexes, paving the way to create new functions for metal complexes. PMID- 28994293 TI - Investigation of the Best Approach for Assessing Human Exposure to Poly- and Perfluoroalkyl Substances through Indoor Air. AB - Per- and polyfluoroalkyl substances (PFASs), including fluorotelomer alcohols (FTOHs), perfluoroalkyl sulfonamidoethanols (FOSEs), and perfluoroalkyl sulfonamides (FOSAs), were assessed in 61 residential indoor air and 15 personal air samples collected in Oslo area, Norway. FTOHs were detected in all samples, and the median concentrations in residential indoor air were 2970, 10400, and 3120 pg m-3 for 6:2, 8:2, and 10:2 FTOH, respectively. This is similar to or higher than previously reported in studies from the same geographical area and worldwide. FOSEs and FOSAs were detected in 49-70% and 7-13% of the residential indoor air samples, respectively. The median FTOH concentrations observed in personal air were 1970, 7170, and 1590 pg m-3 for 6:2, 8:2, and 10:2 FTOH, respectively, which is 30 to 50% lower than the median concentrations in residential indoor air. No FOSEs or FOSAs were detected above the method detection limit (MDL) in the personal air samples. Intakes of perfluorohexanoate (PFHxA), perfluoroheptanoate (PFHpA), perfluorooctanoate (PFOA), perfluorononanoate (PFNA), perfluorodecanoate (PFDA), perfluoroundecanoate (PFUnDA), and perfluorooctyl sulfonate (PFOS) through inhalation and biotransformation of PFAS precursors in air were estimated. Median intakes of 1.7, 0.17, 5.7, 0.57, 1.8, 0.18, and 2.3 pg kg bw-1 day-1 were obtained in residential indoor air, while 1.0, 0.10, 3.3, 0.33, 0.88, and 0.09 pg kg bw-1 day 1 were found in personal air for PFHxA, PFHpA, PFOA, PFNA, PFDA, PFUnDA, and PFOS, respectively. The median PFOA intakes from residential indoor air (5.7 pg kg bw-1 day-1) and personal air (3.3 pg kg bw-1 day-1) were both around 5 orders of magnitude lower than the tolerable daily intake (TDI) reported by the European Food Safety Authority (EFSA). PMID- 28994294 TI - Growth Mechanism and Surface State of CuInS2 Nanocrystals Synthesized with Dodecanethiol. AB - Ternary metal chalcogenide nanocrystals (NCs) offer exciting opportunities as novel materials to be explored on the nanoscale showing optoelectronic properties tunable with size and composition. CuInS2 (CIS) NCs are the most widely studied representatives of this family as they can be easily prepared with good size control and in high yield by reacting the metal precursors (copper iodide and indium acetate) in dodecanethiol (DDT). Despite the widespread use of this synthesis method, both the reaction mechanism and the surface state of the obtained NCs remain elusive. Here, we perform in situ X-ray diffraction using synchrotron radiation to monitor the pre- and postnucleation stages of the formation of CIS NCs. SAXS measurements show that the reaction intermediate formed at 100 degrees C presents a periodic lamellar structure with a characteristic spacing of 34.9 A. WAXS measurements performed after nucleation of the CIS NCs at 230 degrees C demonstrate that their growth kinetics depend on the degree of precursor conversion achieved in the initial stage at 100 degrees C. NC formation requires the cleavage of S-C bonds. We reveal by means of combined 1D and 2D proton and carbon NMR analyses that the generated dodecyl radicals lead to the formation of a new thioether species R-S-R. The latter is part of a ligand double layer, which consists of dynamically bound dodecanethiolate ligands as well as of head-to-tail bound R-S-R molecules. This ligand double layer and a high ligand density (3.6 DDT molecules per nm2) are at the origin of the apparent difficulty to functionalize the surface of CIS NCs obtained with the DDT method. PMID- 28994295 TI - Thermodynamics of Polypeptide Supramolecular Assembly in the Short-Chain Limit. AB - The self-assembly of peptides into ordered supramolecular structures, such as fibrils and crystals, is of relevance in such diverse areas as molecular medicine and materials science. However, little information is available about the fundamental thermodynamic driving forces of these types of self-assembly processes. Here, we investigate in detail the thermodynamics of assembly of diphenylalanine (FF). This dipeptide forms the central motif of the Abeta peptides, which are associated with Alzheimer's disease through their presence in amyloid plaques in the nervous systems of affected individuals. We identify the molecular origins of the self-assembly of FF in aqueous solution, and we evaluate these findings in the context of the aggregation free energies of longer peptides that are able to form amyloid fibrils. We find that the thermodynamics of FF assembly displays the typical characteristics of hydrophobic desolvation processes, and detailed analysis of the temperature dependence of the kinetics of assembly within the framework of crystallization theories reveals that the transition state from solution to crystalline aggregates is enthalpically unfavorable and entropically favorable, qualitatively similar to what has been found for longer sequences. This quantitative comparison of aggregating peptides of very different lengths is the basis of an in-depth understanding of the relationship between sequence and assembly behavior. PMID- 28994296 TI - Nonmonotonic Dependence of Auger Recombination Rate on Shell Thickness for CdSe/CdS Core/Shell Nanoplatelets. AB - Nonradiative Auger recombination limits the efficiency with which colloidal semiconductor nanocrystals can emit light when they are subjected to strong excitation, with important implications for the application of the nanocrystals in light-emitting diodes and lasers. This has motivated attempts to engineer the structure of the nanocrystals to minimize Auger rates. Here, we study Auger recombination rates in CdSe/CdS core/shell nanoplatelets, or colloidal quantum wells. Using time-resolved photoluminescence measurements, we show that the rate of biexcitonic Auger recombination has a nonmonotonic dependence on the shell thickness, initially decreasing, reaching a minimum for shells with thickness of 2-4 monolayers, and then increasing with further increases in the shell thickness. This nonmonotonic behavior has not been observed previously for biexcitonic recombination in quantum dots, most likely due to inhomogeneous broadening that is not present for the nanoplatelets. PMID- 28994297 TI - Some personal reminiscences of the long road to acceptance of the Three Rs. PMID- 28994298 TI - Human aortic endothelial cells respond to shear flow in well-plate microfluidic devices. AB - Although chronic progressive cardiovascular diseases such as atherosclerosis are often challenging to fully model in vitro, it has been shown that certain in vitro methods can effectively evaluate some aspects of disease progression. This has been demonstrated in in vitro and in vivo studies of endothelial cells that have illustrated the effects of nitric oxide (NO) production, filamentous actin (F-actin) formation, and cell and actin angle alignment on vascular function and homeostasis. Systems utilising shear flow have been established, in order to create a physiologically relevant environment for cells that require shear flow for homeostasis. Here, we investigated the use of a well-plate microfluidic system and associated devices (0-20dyn/cm2) to demonstrate applied shear effects on primary Human Aortic Endothelial Cells (HAECs). Changes in cell and actin alignment in the direction of flow, real-time production of NO and gross cell membrane shape changes in response to physiological shear flow were observed. These commercial systems have a range of potential applications, including within the consumer and pharmaceutical industries, thereby reducing the dependency on animal testing for regulatory safety assessments. PMID- 28994299 TI - Use of the Bovine Udder Skin model to evaluate the tolerability of Mesem cosmetic cream. AB - Observational studies of Mesem cream (based on Mesembryanthemum crystallinum L. plant extract) found that it had positive effects on skin hydration and smoothing of the skin. However, some patients reported skin irritation effects. The current study evaluated the skin tolerability of Mesem cream, as compared to the carrier cream (without the active ingredient), by using the isolated perfused bovine udder skin model. The primary outcomes investigated were cytotoxicity (i.e. cell viability), assessed with the MTT assay, and irritancy and inflammation, assessed by measuring PGE2 tissue levels. A total reaction score was calculated by combining the results for each parameter. In the case of a single topical application, significant differences were found between the carrier cream and the Mesem cream. While the application of carrier cream resulted in low cytotoxicity (-8.4% change in viability, as compared to the untreated control), the Mesem cream was more cytotoxic (-18.7% change). In addition, one hour after application, PGE2 levels were higher in Mesem cream-treated skin, as compared to carrier cream-treated skin (16.6% versus 11.3%). Further experiments (tape stripped skin and repeated application) also found significant differences between the two creams in the results obtained. Evaluation of the effectiveness, safety and tolerability of phyto-cosmetic products is important. Our results confirmed the findings of two previous human observational studies (the human patch test and open application study). Future experiments to understand the underlying principles of its effectiveness, safety and tolerability should include extracts of M. crystallinum L. juice, as well as the Mesem cream itself. PMID- 28994300 TI - In vitro models as a platform to investigate traumatic brain injury. AB - Traumatic Brain Injury (TBI) remains a significant cause of mortality and morbidity, affecting individuals of all age groups. Much remains to be learned about its complex pathophysiology, with a view to designing effective neuroprotective strategies to protect sublethally injured brain tissue that would otherwise die in secondary injury processes. Experimental in vivo models offer the potential to study TBI in the laboratory, however, treatments that were neuroprotective in animals have, thus far, largely failed to translate in human clinical studies. In vitro models of neurotrauma can be used to study specific pathophysiological cascades - individually and without confounding factors - and to test potential neuroprotective strategies. These in vitro models include transection, compression, barotrauma, acceleration, hydrodynamic, chemical injury and cell-stretch methodologies. Various cell culture systems can also be utilised, including brain-on-a-chip, immortalised cell lines, primary cultures, acute preparations and organotypic cultures. Potential positive outcomes of the increased use of in vitro platforms to study TBI would be the refinement of in vivo experiments, as well as enhanced translation of the results into clinically meaningful neuroprotective strategies for the future. In addition, the replacement of in vivo experiments by suitable in vitro studies would lead to a welcome reduction in the numbers of animal procedures in this ethically challenging field. PMID- 28994301 TI - Medact/IPPNW Health Through Peace York University conference statement: an introduction. PMID- 28994302 TI - Observing eye movements and the influence of cognition during a symbol search task: a comparison across three age groups. AB - This study examined eye movements during a visual search task as well as cognitive abilities within three age groups. The aim was to explore scanning patterns across symbol grids and to better understand the impact of symbol location in AAC displays on speed and accuracy of symbol selection. For the study, 60 students were asked to locate a series of symbols on 16 cell grids. The EyeLink 1000 was used to measure eye movements, accuracy, and response time. Accuracy was high across all cells. Participants had faster response times, longer fixations, and more frequent fixations on symbols located in the middle of the grid. Group comparisons revealed significant differences for accuracy and reaction times. The Leiter-R was used to evaluate cognitive abilities. Sustained attention and cognitive flexibility scores predicted the participants' reaction time and accuracy in symbol selection. Findings suggest that symbol location within AAC devices and individuals' cognitive abilities influence the speed and accuracy of retrieving symbols. PMID- 28994304 TI - An exploration of the experience of using calendar reminders for people with dementia and family carers. AB - People with dementia and family carers often use calendars to support time orientation to maintain routine. However, little is known about the use of calendars as a compensatory strategy. This study examines the experience and practicalities of using calendar reminders from the perspective of people with dementia and family carers. Six dyads were recruited and interviewed at home. Interpretative Phenomenological Analysis was used to develop a narrative interpreted from an occupational therapy perspective. The themes were reflected on during two subsequent focus groups. Findings suggested that calendars are used either intensively as external memory records or more casually and randomly for reassurance. The familiarity and location of the calendar and its utility to the person with dementia and carer, all contribute to its efficacy. For carers the experience of supporting calendar reminders encompasses practical, cognitive and emotional effort. There was little awareness amongst participants of electronic assistive technology. PMID- 28994303 TI - The lines are open: An artist's experience of working with dementia research. AB - This paper offers a first-hand account from a visual artist working with people living with a rare dementia. It explores the processes and motivations involved in situating an individual artistic practice in the field of dementia research. The paper discusses the potential role of creative art-making for neuropsychological testing and some of the complexities of interpretation that this involves. This account also highlights the ways in which working with people with dementia can be personally and artistically transformative. PMID- 28994306 TI - Pharmacological treatments and infectious diseases in pediatric inflammatory bowel disease. AB - INTRODUCTION: The incidence of pediatric inflammatory bowel disease (IBD) is rising, as is the employment of immunosuppressive and biological drugs. Most patients with IBD receive immunosuppressive therapies during the course of the disease. These molecules are a double-edged sword; while they can help control disease activity, they also increase the risk of infections. Therefore, it is important that pediatricians involved in primary care, pediatric gastroenterologists, and infectious disease physicians have a thorough knowledge of the infections that can affect patients with IBD. Areas covered: A broad review of the major infectious diseases that have been reported in children and adolescents with IBD was performed, and information regarding surveillance, diagnosis and management were updated. The possible correlations with IBD pharmacological tools are discussed. Expert commentary: Opportunistic infections are possible in pediatric IBD, and immunosuppressive and immunomodulator therapy seems to play a causative role. Heightened awareness and vigilant surveillance leading to prompt diagnosis and treatment are important for optimal management. PMID- 28994305 TI - Plant homeodomain finger protein 2 as a novel IKAROS target in acute lymphoblastic leukemia. AB - AIM: Clinical significance of plant homeodomain finger 2 (PHF2) expressions is explored in acute lymphoblastic leukemia (ALL) patients. METHODS: mRNA level was examined by qPCR. The retroviral gene expression, shRNA knockdown and chromatin immunoprecipitation are used to observe IKAROS regulation on PHF2 transcription. RESULTS: PHF2 expression is significantly reduced in subsets of ALL patients, and PHF2 low expression correlates with leukemia cell proliferation and an elevation of several poor prognostic markers in B-cell ALL. IKAROS directly promotes PHF2 expression and patients with IKAROS deletion have significantly lower PHF2 expression. Casein kinase II (CK2) inhibitor significantly promotes PHF2 expression in an IKAROS-dependent manner, and casein kinase II inhibitor treatment also results in an increase of PHF2 expression and enrichment of IKAROS and H3K4me3 at PHF2 promoter in primary cells. CONCLUSION: Our results demonstrate that the IKAROS promotes PHF2 expression, and suggest that PHF2 low expression works with the IKAROS gene deletion to drive oncogenesis of ALL. PMID- 28994307 TI - Alert Workplace From Healthcare Workers' Perspective: Behavioral and Environmental Strategies to Improve Vigilance and Alertness in Healthcare Settings. AB - OBJECTIVE: This study aims to identify the behavioral and environmental strategies that healthcare workers view as helpful for managing sleepiness, improving alertness, and therefore optimizing workplace safety. BACKGROUND: Reduced alertness is a common issue in healthcare work environments and is associated with impaired cognitive performance and decision-making ability as well as increased errors and injuries. METHOD: We surveyed 136 healthcare professionals at a primary care clinic, an acute care hospital, and a mental health clinic. Nonstructured, semistructured, and structured questionnaires were used to elicit relevant information which was analyzed using qualitative content analysis and logistic regression models, respectively. RESULTS: In order by frequency of endorsement: dietary intervention; physical mobility; cognitive, sensory, or social stimulation; personal lifestyle strategies; and rest/nap opportunities were reported as behavioral strategies used to address workplace alertness. Compared to other environmental features, daylight and thermal comfort were perceived to be more important to addressing workplace alertness ( p < .05). CONCLUSIONS: By optimizing the physical environment and organizational policies and providing education programs, we have an opportunity to support healthcare professionals in managing sleepiness and maintaining alertness at work. In addition, such system level interventions may reduce unhealthy choices such as frequent caffeine intake to keep alert. The development of multidisciplinary evidence-based guidelines is needed to address sleepiness and alertness to improve workplace safety in healthcare facilities. PMID- 28994308 TI - Critical health psychology in New Zealand: Developments, directions and reflections. AB - We examine how critical health psychology developed in New Zealand, taking an historical perspective to document important influences. We discuss how academic appointments created a confluence of critical researchers at Massey University, how interest in health psychology arose and expanded, how the critical turn eventuated and how connections, both local and international, were important in building and sustaining these developments. We discuss the evolution of teaching a critical health psychology training programme, describe the research agendas and professional activities of academic staff involved and how this sustains the critical agenda. We close with some reflections on progress and attainment. PMID- 28994309 TI - Overview of small bowel angioectasias: clinical presentation and treatment options. AB - INTRODUCTION: Elderly patients with multiple co-morbidities are at an increased risk of developing small bowel angioectasias. Treating these lesions can be both challenging and costly with patients requiring extensive investigations and recurrent admissions for iron infusions and blood transfusions as well as invasive procedures. This review presents treatment options and describes in detail drugs that should be considered whilst taking into account their effectiveness and their safety profile. Areas covered: A PubMed search was carried out using the following keywords: small bowel angiodysplasias, small bowel angioectasias, small bowel bleeding and obscure gastrointestinal bleeding to assess existing evidence. The pathophysiology and risk factors are covered in this review together with appropriate methods of investigation and management. Treatment options discussed are endoscopic measures, surgical options and pharmacotherapy. The role of serum biomarkers is also discussed. Expert commentary: Future work should be directed at alternative drugs with a good safety profile that target biomarkers. Novel pharmacotherapy directed at biomarkers could potentially provide a non-invasive treatment option for angioectasias particularly in the elderly where management can be challenging. PMID- 28994311 TI - Death associated with intravenous turmeric (Curcumin) preparation. PMID- 28994310 TI - Pharmacogenetic considerations for HIV treatment in different ethnicities: an update. AB - INTRODUCTION: Variations in the human genome sequence sometimes play an important role in pharmacokinetics and/or pharmacodynamics. Previous studies have demonstrated a high degree of variation both between and within different ethnic populations. Areas covered: This review sought to summarize key SNPs in CYP2B6, CYP3A enzymes, CYP2C enzymes, UGT2 enzymes, ABCB1, ABCC2, SLCO1B1, NR1I2, and NR1I3 that have previously been associated with variability in antiretroviral pharmacokinetics. Additionally, the impact of ethnicity in these pharmacogenetics studies is discussed, and variation in findings between different ethnic groups is reviewed. A literature search of relevant published work was conducted between April 2017 and September 2017 utilizing the following databases: PubMed, Google Scholar, Web of Science, and Ensembl. Keywords used included drug name, rs (SNP identifier) number, and known effect (if applicable). This report highlights the variation observed between different ethnic populations and subsequently the importance of stratification within pharmacogenetic studies. Expert opinion: Utilization of these findings in future pharmacogenetics studies would aid in the understanding of the extent and impact of genetic variants in different populations and the consequences this has for achieving sustained virological response to antiretroviral therapy. PMID- 28994312 TI - Association between re-admission rate and hospital characteristics for ischemic heart disease. AB - OBJECTIVE: Hospital re-admission is considered an important marker of patient health outcomes and healthcare system performance. Korea introduced the Korean Diagnosis Procedure Combination (KDPC) for all regional public hospitals in July 2012. This study examined re-admission rates within 30 days to assess whether the hospital payment system is associated with the re-admission rate, focusing on ischemic heart disease. METHODS: A cross-sectional study was conducted using national claims data for 2013. We analyzed data of patients with a major diagnosis of ischemic heart disease who were admitted to general hospitals with more than 500 beds in Korea. Of the eight general hospitals, two that have been operating under the new Korean payment system were public hospitals using the KDPC, and the remaining six were private general hospitals with fee for service (FFS) systems. Multiple logistic regression analysis was used to identify associations between re-admission rate and hospital characteristics. RESULTS: The study analyzed 4,290 cases (889 cases in KDPC and 3,401 cases in FFS). The 30-day unplanned re-admission rate was higher in KDPC than in FFS (7.9% vs 5.6%, respectively). The unplanned re-admission odds ratios of KDPC was 1.74. CONCLUSIONS: KDPC had higher 30-day unplanned re-admissions rates than did FFS. PMID- 28994313 TI - TRAIL and curcumin codelivery nanoparticles enhance TRAIL-induced apoptosis through upregulation of death receptors. AB - Active targeting nanoparticles were developed to simultaneously codeliver tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and Curcumin (Cur). In the nanoparticles (TRAIL-Cur-NPs), TRAIL was used as both active targeting ligand and therapeutic agent, and Cur could upregulate death receptors (DR4 and DR5) to increase the apoptosis-inducing effects of TRAIL. Compared with corresponding free drugs, TRAIL-Cur-NPs group showed enhanced cellular uptake, cytotoxicity and apoptosis induction effect on HCT116 colon cancer cells. In addition, in vivo anticancer studies suggested that TRAIL-Cur-NPs had superior therapeutic effect on tumors without obvious toxicity, which was mainly due to the high tumor targeting and synergistic effect of TRAIL and Cur. The synergistic mechanism of improved antitumor efficacy was proved to be upregulation of DR4 and DR5 in tumor cells induced by Cur. Thus, the prepared codelivery nanoparticles may have potential applications in colorectal cancer therapy. PMID- 28994314 TI - Preventing liver fibrosis in patients with NAFLD and the road ahead. PMID- 28994315 TI - First-line treatment disruption among post-menopausal women with HR+/HER2- metastatic breast cancer: a retrospective US claims study. AB - OBJECTIVE: This study assessed disruption of first-line treatments initiated after the approval of the first CDK 4/6 inhibitor, palbociclib, among post menopausal women with HR+/HER2- metastatic breast cancer (mBC) in the US. METHODS: Post-menopausal women with HR+/HER2- mBC who initiated first-line endocrine therapy or chemotherapy (index therapy) between February 3, 2015 (palbociclib approval date) and February 29, 2016 (end of data) were identified from the Symphony Source Lx database. Patients were required to have continuous quarterly activity (defined as >=1 pharmacy or medical claim) for 12 months prior to and 1 month after the initiation of the index therapy (index date). Treatment disruption was defined as a treatment gap of >=60 days or adding an agent after the original therapy. Kaplan-Meier analyses were conducted to estimate treatment disruption rates during the 6 months following the index date. Patients without treatment disruption were censored at the end of continuous quarterly activity or end of data. RESULTS: A total of 8,160 and 2,153 eligible patients initiated endocrine therapy or chemotherapy as their first-line mBC treatment, with a median follow-up of 6.7 and 7.6 months, respectively. The three most prevalent metastatic sites were bone (28.1-42.2%), liver (8.8-17.3%), and lung (8.6-9.5%). Overall, 37.7% (n = 3,074) of patients receiving endocrine therapy and 86.1% (n = 1,852) of patients receiving chemotherapy encountered treatment disruption at 6 months (log-rank test p < .05). CONCLUSIONS: Treatment disruption rates of first line therapies were sub-optimal among post-menopausal women with HR+/HER2- mBC, primarily driven by chemotherapy users. New therapies or interventions are needed to reduce treatment disruption in this patient population. PMID- 28994316 TI - Life on the ground floor: letters from the edge of emergency medicine. PMID- 28994317 TI - Isolated cervical anterior spinal artery aneurysm: case report. AB - Isolated cervical anterior spinal artery (CASA) aneurysms are extremely rare with most of them mostly associated with arteriovenous malformation. The underlying pathology is not known but some factors leading to the aneurysm are inflammatory, infection and connective tissue disorders. Trauma with formation of pseudoaneurysm has also been reported. We report a case which presented with fourth ventricle bleed and was managed successfully with conservative treatment. PMID- 28994318 TI - Tungsten (W) bioavailability in paddy rice soils and its accumulation in rice (Oryza sativa). AB - The aim of this study was to investigate the accumulation characteristics of tungsten (W) by different indica rice cultivars from the soil and to assess the potential risks to human health via dietary intake of W in rice consumption. A total of 153 rice (ear) samples of 15 cultivars and the corresponding surface soil samples were collected from 7 cities in Fujian Province of southeastern China. The available soil W were extracted using H2C2O4.2H2O-(NH4)2C2O4.H2O at pH 3.3). Results showed that the total soil W ranged from 2.03 mg kg-1 to 15.34 mg kg-1 and available soil W ranged from 0.03 mg kg-1 to 1.61 mg kg-1. The W concentration in brown rice varied from 7 MUg kg-1 to 283 MUg kg-1 and was significantly correlated with the available soil W. The highest mean TFavail (transfer factor based on available soil W) was 0.91 for Te-you 627 (hybrid, indica rice), whereas the lowest was 0.08 for Yi-you 673 (hybrid, indica rice). The TFavail decreased with the increase in available soil W, clay content, and cation exchange capacity. The consumption of the brown rice produced from the investigated areas in some cultivars by the present study may cause risks to human health. PMID- 28994319 TI - A review of clinical safety data for sumatriptan nasal powder administered by a breath powered exhalation delivery system in the acute treatment of migraine. AB - INTRODUCTION: AVP-825 (sumatriptan nasal powder) is an FDA-approved intranasal medication delivery system containing low-dose sumatriptan powder for acute treatment of migraine with or without aura in adults. AVP-825 utilizes unique nasal anatomy features to avoid limitations of other intranasal delivery methods. Areas covered: Literature search terms: 'AVP-825', 'sumatriptan nasal powder', 'intranasal sumatriptan', 'sumatriptan safety', 'sumatriptan acute migraine'. Pharmacokinetic, Phase 2/3 studies, reviews (AVP-825) and metanalyses/reviews (sumatriptan) were evaluated. Expert opinion: AVP-825 provides a more efficient sumatriptan delivery method versus other formulations. Pharmacokinetics showed that a single dose of AVP-825 (22 mg) delivers 15-16 mg sumatriptan and produces significantly lower exposure than oral or injectable formulations, which may translate into a better safety/tolerability profile. AVP-825 was well tolerated in controlled trials, with the most common adverse events localized at the administration-site (abnormal taste, nasal discomfort); these were mostly mild, leading to only one discontinuation. Compared to 100 mg oral sumatriptan, AVP-825 had a significantly lower rate of atypical sensations across multiple attacks. AVP-825 has the advantage of early efficacy onset associated with faster absorption at a lower delivered dose than liquid nasal spray or oral formulations. AVP-825 provided earlier efficacy (within 30 min) vs. 100 mg oral sumatriptan and similar sustained efficacy. AVP-825 offers the benefits of a non oral, low-dose, tolerable acute migraine medication. PMID- 28994320 TI - Unravelling the core microbiome of biofilms in cooling tower systems. AB - In this study, next generation sequencing and catalyzed reporter deposition fluorescence in situ hybridization, combined with confocal microscopy, were used to provide insights into the biodiversity and structure of biofilms collected from four full-scale European cooling systems. Water samples were also analyzed to evaluate the impact of suspended microbes on biofilm formation. A common core microbiome, containing members of the families Sphingomonadaceae, Comamonadaceae and Hyphomicrobiaceae, was found in all four biofilms, despite the water of each coming from different sources (river and groundwater). This suggests that selection of the pioneer community was influenced by abiotic factors (temperature, pH) and tolerances to biocides. Members of the Sphingomonadaceae were assumed to play a key role in initial biofilm formation. Subsequent biofilm development was driven primarily by light availability, since biofilms were dominated by phototrophs in the two studied 'open' systems. Their interactions with other microbial populations then shaped the structure of the mature biofilm communities analyzed. PMID- 28994321 TI - Heatable carbon nanotube composite membranes for sustainable recovery from biofouling. AB - Membrane filtration is one of the most reliable methods for water treatment. However, wider application is limited due to biofouling caused by accumulation of microorganisms on the membrane surface. This report details a heatable carbon nanotube composite membrane with self-cleaning properties for sustainable recovery from biofouling. Microfiltration polycarbonate/carbon-nanotubes hybrid membranes were fabricated using drawable nanotubes that maintained the porosity and provided electrical conductivity to the membrane. Less than 25 V potential and 2-3 W power increase membrane temperature to 100 degrees C in ~10 s. This temperature is above what most microbial life, bacteria and viruses can handle. When this membrane was employed, filtered Escherichia coli collected on its surface were successfully annihilated within 1 min. Ohmic heating of this membrane could be an effective solution to combat biofouling and complications associated with membrane-based filtration. This is a novel and highly desirable approach to combat biofouling, due to its simplicity and economic advantage. PMID- 28994322 TI - Viewpoints of Parents and Nurses on How to Design Products to Enhance Parent Infant Bonding at Neonatal Intensive Care Units: A Qualitative Study Based on Existing Designs. AB - AIM: To investigate how product design can be used to improve parent-infant bonding in a neonatal intensive care unit. BACKGROUND: Impaired parent-infant bonding is an inevitable consequence of premature birth, which negatively influences development. Products, systems, or services that support the bonding process might counter these negative influences. METHOD: The first step was to trace existing products by performing a literature search in PubMed, the university library, and Google. The identified existing designs were then used in semistructured interviews with nurses and parents to get insights into their desires and recommendations for product design to enhance bonding. Interviews contained open questions and a multiple-choice questionnaire based on the literature search. RESULTS: In total, 17 existing design types were used in interviews with 11 parents and 23 nurses. All nurses explicitly stated that practicality was the first criterion designs aimed at enhancing bonding definitely had to meet. All parents indicated that they would like to use a design to enhance bonding if that would contribute to their child's health and development. For both parents and nurses, the most valuable way to enhance bonding seemed to be products to improve Kangaroo care; however, their specific desires varied substantially. Therefore, seven recurring themes were defined, resulting in nine general recommendations and six opportunities intended to enhance parent-infant bonding. CONCLUSION: This study provides design recommendations and opportunities based on parents' and nurses' expert opinions. Designing to enhance bonding is considered valuable; however, designs should match the stakeholders' desires and conditions. PMID- 28994323 TI - Atezolizumab in invasive and metastatic urothelial carcinoma. AB - INTRODUCTION: Until recently, there has been little advancement in the management of invasive and metastatic urothelial cancer in over 30 years, and outcomes with cisplatin-based chemotherapy remain unchanged. Inhibitors targeting PD-1 signaling on cytotoxic T-cells have revolutionized bladder cancer therapy leading to durable responses. Atezolizumab is an engineered humanized anti-PD-L1 monoclonal antibody that inhibits PD-L1 binding to PD-1 and B7.1, enhancing immune-mediated tumor killing and is currently approved as second-line treatment after failure of platinum-based chemotherapy as well as first-line in cisplatin ineligible patients. Areas covered: This article summarizes all reported phase I, II and III clinical trials that assessed the safety and efficacy of atezolizumab in the treatment of locally advanced and metastatic urothelial carcinoma. Expert commentary: Treatment with atezolizumab showed durable response and a toxicity profile that appears favorable to cytotoxic chemotherapy historically in the treatment of metastatic urothelial cancer among individuals who had progressed after prior platinum-based therapy and among those ineligible for treatment with first-line cisplatin. PD-L1 expression and tumor mutation load associate with response, however further research is needed to identify additional markers to improve prediction of response to atezolizumab. PMID- 28994324 TI - Self-assembling HA/PEI/dsRNA-p21 ternary complexes for CD44 mediated small active RNA delivery to colorectal cancer. AB - Our previous work proved that sequence specific double strand RNA (dsRNA-p21) effectively activated p21 gene expression of colorectal cancer (CRC) cells and consequently suppressed CRC growth. However, efficient delivery system is a significant challenge to achieve sufficient therapy. In this study, a self assembled HA/PEI/dsRNA-p21 ternary complex (TC-dsRNA-p21) was developed for the tumor-target delivery of dsRNA-p21 into CRC cells. Hyaluronic acid (HA) was introduced to shield the PEI/dsRNA-p21 binary complexes (BC-dsRNA-p21) for reducing the cytotoxicity of PEI and for increasing the tumor-targeted intracellular uptake by cancer cells through HA-CD44 mediated endocytosis. Comparing to the BC-dsRNA-p21, the TC-dsRNA-p21 showed increase in size, decrease in zeta potential, low cytotoxicity as well as high stability in physiological conditions due to the anionic shielding. Confocal microscopy analysis and flow cytometry confirmed that TC-dsRNA-p21 had high transfection efficiency in the CD44-abundant Lovo cells, as compared with binary complex. In vitro physiological experiment showed that, comparing to the control group, the TC-dsRNA-p21 effectively activated the expression of p21 mRNA and P21 protein, causing blockage of cell cycle at G0/G1 phase and suppression of cancer cell proliferation as well as colony formation. Furthermore, in vivo distribution experiment demonstrated that the TC-dsRNA-p21 could effectively accumulate at rectal wall for up to 10 h, following in situ application. These findings indicated that TC-dsRNA-p21 might hold great potential for delivering dsRNA-p21 to treat CRC. PMID- 28994325 TI - Folic acid conjugated PEG coated gold-iron oxide core-shell nanocomplex as a potential agent for targeted photothermal therapy of cancer. AB - This study reports the synthesis and characterization of poly(ethylene glycol) coated gold@iron oxide core-shell nanoparticles conjugated with folic acid (FA PEG-Au@IONP). Also, targeted therapeutic properties of such a nanocomplex were studied on human nasopharyngeal carcinoma cell line KB and human breast adenocarcinoma cell line MCF-7 in vitro. The synthesized nanocomplex was characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), UV-Vis spectroscopy, vibrating sample magnetometry (VSM), and Fourier transform infrared (FTIR) spectroscopy. The photothermal effects of nanocomplex on both KB and MCF-7 cell lines were studied. Cell death and apoptosis were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry using an annexin V-fluorescein isothiocyanate/propidiumiodide apoptosis detection kit. It was found that nanocomplex is spherical in shape and its size is approximately 60 nm. UV-vis spectrum showed that nanocomplex has appropriate absorption near infrared region. FTIR spectra obtained from nanocomplex before and after conjugation with FA confirmed the formation of folate conjugated nanocomplex. Significant cell lethality was observed for KB (~62%) and MCF-7 (~33%) cells following photothermal therapy. Also, it was found that majority of the cell deaths were related to apoptosis process. It can be concluded that, the synthesized nanocomplex is an effective and promising multifunctional nanoplatform for targeted photothermal therapy of cancer. PMID- 28994326 TI - When things get complicated: At-risk attachment in children and adolescents with chronic pain. AB - Pain is a signal of danger, and danger activates the attachment system. When a parent responds to a child's pain with appropriate protection and comfort, more often than not, the pain resolves. But what happens in families when a child's pain becomes chronic and continues to signal a danger that has long passed? This study explored patterns of attachment in 48 children and adolescents with chronic functional pain and 48 healthy controls using structured attachment interviews. Patterns of attachment were identified using the Dynamic Maturational Model of Attachment. Compared to controls, children and adolescents with chronic functional pain were classified into at-risk patterns of attachment (chi2 = 76.4, df = 2, p < .001) and had higher rates of unresolved loss and trauma (chi2 = 10.8, df = 1, p = .001), suggesting a long-standing history of relational stress and the disruption of nurturing relationships. The findings suggest that the quality of attachment relationships contribute to the development and maintenance of chronic functional pain. Ongoing anxiety within the attachment relationship, combined with unresolved loss and trauma, may function much like catastrophising, contributing to chronic functional pain by activating the body's arousal systems. The assessment process for chronic functional pain should include a family assessment to identify ruptures in attachment relationships, as well as unresolved loss and trauma events that need to be addressed through family interventions or individual therapy. PMID- 28994327 TI - Mental health services for our most vulnerable children. PMID- 28994328 TI - Th17/Treg immunoregulation and implications in treatment of sulfur mustard gas induced lung diseases. AB - INTRODUCTION: Sulfur mustard (SM) is an extremely toxic gas used in chemical warfare to cause massive lung injury and death. Victims exposed to SM gas acutely present with inhalational lung injury, but among those who survive, some develop obstructive airway diseases referred to as SM-lung syndrome. Pathophysiologically, SM-lung shares many characteristics with smoking-induced chronic obstructive pulmonary disease (COPD), including airway remodeling, goblet cell metaplasia, and obstructive ventilation defect. Some of the hallmarks of COPD pathogenesis, which include dysregulated lung inflammation, neutrophilia, recruitment of interleukin 17A (IL -17A) expressing CD4+T cells (Th17), and the paucity of lung regulatory T cells (Tregs), have also been described in SM-lung. Areas covered: A literature search was performed using the MEDLINE, EMBASE, and Web of Science databases inclusive of all literature prior to and including May 2017. Expert commentary: Here we review some of the recent findings that suggest a role for Th17 cell-mediated inflammatory changes associated with pulmonary complications in SM-lung and suggest new therapeutic approaches that could potentially alter disease progression with immune modulating biologics that can restore the lung Th17/Treg balance. PMID- 28994329 TI - The value of self-medication: summary of existing evidence. AB - AIM: The aim of this review was to identify the international evidence that is currently available on the economic value of self-care through responsible self medication, in terms of the measures related to access to treatment, time, and productivity. METHODS: A targeted literature search was conducted for 1990-2016, including data gathered from members of the World Self-Medication Industry and searches on PubMed, EBSCOHost, and Google Scholar. Specific searches of individual drug classes known to be switched to non-prescription status in this period were also conducted. RESULTS: A total of 71 articles were identified, of which 17 (11 modeling studies, six retrospective analyses) were included in the review. Evidence from modeling studies and retrospective analyses of grouped data across a range of common conditions for which non-prescription medications are available in different countries/regions showed that the use of non-prescription products for the treatment of common conditions or for symptom management (e.g. allergies, chronic pain, migraine, vaginitis, gastrointestinal symptoms, or common cold symptoms) had considerable value to patients, payers, and employers alike in terms of cost savings and improved productivity. Potential benefits of self-medication were also identified in preventative healthcare strategies, such as those for cardiovascular health and osteoporosis. LIMITATIONS: This review was limited by a targeted, but non-systematic approach to literature retrieval, as well as the inclusion of unpublished reports/white papers and patient self reported data. CONCLUSIONS: The evidence identified in this literature review shows that responsible, appropriate self-medication with non-prescription products can provide significant economic benefits for patients, employers, and healthcare systems worldwide. PMID- 28994330 TI - Molecular mechanisms and theranostic potential of miRNAs in drug resistance of gastric cancer. AB - INTRODUCTION: Systemic chemotherapy is a curative approach to inhibit gastric cancer cells proliferation. Despite the great progress in anti-cancer treatment achieved during the last decades, drug resistance and treatment refractoriness still extensively persists. Recently, accumulating studies have highlighted the role of miRNAs in drug resistance of gastric cancers by modulating some drug resistance-related proteins and genes expression. Pre-clinical reports indicate that miRNAs might serve as ideal biomarkers and potential targets, thus holding great promise for developing targeted therapy and personalized treatment for the patients with gastric cancer. Areas covered: This review provide a comprehensive overview of the current advances of miRNAs and molecular mechanisms underlying miRNA-mediated drug resistance in gastric cancer. We particularly focus on the potential values of drug resistance-related miRNAs as biomarkers and novel targets in gastric cancer therapy and envisage the future research developments of these miRNAs and challenges in translating the new findings into clinical applications. Expert opinion: Although the concrete mechanisms of miRNAs in drug resistance of gastric cancer have not been fully clarified, miRNA may be a promising theranostic approach. Further studies are still needed to facilitate the clinical applications of miRNAs in drug resistant gastric cancer. PMID- 28994331 TI - Evaluating the involvement of cerebral microvascular endothelial Na+/K+-ATPase and Na+-K+-2Cl- co-transporter in electrolyte fluxes in an in vitro blood-brain barrier model of dehydration. AB - The blood-brain barrier (BBB) is involved in brain water and salt homeostasis. Blood osmolarity increases during dehydration and water is osmotically extracted from the brain. The loss of water is less than expected from pure osmotic forces, due to brain electrolyte accumulation. Although the underlying molecular mechanisms are unresolved, the current model suggests the luminally expressed Na+ K+-2Cl- co-transporter 1 (NKCC1) as a key component, while the role of the Na+/K+ ATPase remains uninvestigated. To test the involvement of these proteins in brain electrolyte flux under mimicked dehydration, we employed a tight in vitro co culture BBB model with primary cultures of brain endothelial cells and astrocytes. The Na+/K+-ATPase and the NKCC1 were both functionally dominant in the abluminal membrane. Exposure of the in vitro BBB model to conditions mimicking systemic dehydration, i.e. hyperosmotic conditions, vasopressin, or increased [K+]o illustrated that NKCC1 activity was unaffected by exposure to vasopressin and to hyperosmotic conditions. Hyperosmotic conditions and increased K+ concentrations enhanced the Na+/K+-ATPase activity, here determined to consist of the alpha1 beta1 and alpha1 beta3 isozymes. Abluminally expressed endothelial Na+/K+-ATPase, and not NKCC1, may therefore counteract osmotic brain water loss during systemic dehydration by promoting brain Na+ accumulation. PMID- 28994332 TI - Ultrasonography findings and physical examination outcomes in dancers with and without patellofemoral pain. AB - OBJECTIVES: To identify whether a physical examination for patello-femoral pain (PFP) is related to ultrasonography findings at the knee, and to identify possible factors related to PFP in young dancers. METHODS: Sixty-seven young female dancers (7th grade, aged 12.8 +/- 0.5) from three schools with identical special dance programs were included in the study. All the dancers were interviewed for demographic details, dance background, and training intensity; were evaluated for anthropometric measurements; underwent physical examination of both knees for PFP and for knee range of motion (ROM); and, had ultrasonography assessment for pathologies and of anatomical parts of their knees. RESULTS: PFP was found in 54.5% of the 134 knees physically examined. In ultrasonography assessment, infra-articular effusion was found in 46.2% of the knees examined. H/week of dance practice was significantly higher among dancers with PFP (in both knees) compared with dancers with no PFP (p < .05). Knees with PFP had a significantly higher prevalence of intra articular effusion (p = .018) and higher prevalence of genu-recurvatum (p = .042). Knees with PFP had significantly greater growth plate width-anterior tibial tuberosity (p = .022) and a greater bony trochlear groove angle (p = .048). CONCLUSION: This study describes the relationship between physical examination for PFP and the sonographic findings, and the factors related to knee injuries. The results showed a high prevalence of PFP and intra articular knee effusion among young dancers at the age of 12-13 years; and, that the number of hours of practice and anatomical structure are related to PFP. Our results should alert physicians, physiotherapists, athletic trainers and dance teachers to the need for devising modifications of training and injury prevention strategies from a young age (<12 years old). PMID- 28994333 TI - Pyruvate kinase activators as a therapy target: a patent review 2011-2017. AB - INTRODUCTION: It is well known that cancer cells have an altered metabolism both to meet the energy needs and to provide initial molecules for the synthesis of macromolecules. To cope with the new metabolic state, different forms of certain enzymes are expressed in extreme amounts. These enzymes are seen as very attractive targets to deal with cancer. Pyruvate kinases isoenzyme M2 (PKM2) is a key enzyme that determines whether glucose is used for energy or synthesis of biosynthetic molecules. The dimeric form of PKM2 main form in several cancer cells serves the formation of synthetic precursors required for the cell growth and proliferation from glycolytic intermediates. Areas covered: This article reviews appropriate publications on PKM2 activators from the points of view of synthesis and biological activities between 2011-2017. Herein, based on the chemical structure, PKM2 activators are classified into sulfonamide, phenolic, carboxamide and pyridopyrimidinone derivatives. Expert opinion: PKM2 activation inhibits cell growth and proliferation by decreasing a number of biomolecules required for cell building. Therefore; PKM2 activators are considered as an ideal drug for or the treatment of many cancer pathogens. It is necessary to discover new, more active and selective compounds for PKM2 activation. PMID- 28994334 TI - Clinical and economic benefits of professional CGM among people with type 2 diabetes in the United States: analysis of claims and lab data. AB - BACKGROUND: It is estimated that one in 10 people in the US have a diagnosis of diabetes. Type 2 diabetes accounts for 95% of all cases in the US, with annual costs estimated to be $246 billion per year. This study investigated the impact of a glucose-measuring intervention to the burden of type 2 diabetes. OBJECTIVE: This analysis seeks to understand how professional continuous glucose monitoring (professional CGM) impacts clinical and economic outcomes when compared to patients who are not prescribed professional CGM. METHODS: This study utilized a large healthcare claims and lab dataset from the US, and identified a cohort of patients who were prescribed professional CGM as identified by CPT codes 95250 and 95251. It calculated economic and clinical outcomes 1 year before and 1 year after the use of professional CGM, using a generalized linear model. RESULTS: Patients who utilized professional CGM saw an improvement in hemoglobin A1C. The "difference-in-difference" calculation for A1C was shown to be -0.44%. There was no statistically significant difference in growth of total annual costs for people who used professional CGM compared to those who did not ($1,270, p = .08). Patients using professional CGM more than once per year had a -$3,376 difference in the growth of total costs (p = .05). Patients who used professional CGM while changing their diabetes treatment regimen also had a difference of -$3,327 in growth of total costs (p = .0023). CONCLUSION: Significant clinical benefits were observed for patients who used professional CGM. Economic benefits were observed for patients who utilized professional CGM more than once within a 1-year period or who used it during a change of diabetes therapy. This suggests that professional CGM may help decrease rising trends in healthcare costs for people with type 2 diabetes, while also improving clinical outcomes. PMID- 28994335 TI - Erratum. PMID- 28994336 TI - Chronic hypertension: effect of blood pressure control on pregnancy outcome. AB - OBJECTIVE: To examine whether in patients with CH and mild to moderate hypertension the level of control of blood pressure during pregnancy has a beneficial or adverse effect on the risk of PE or SGA. METHODS: We performed a systematic review and meta-analysis of randomized controlled trials of patients with mild to moderate CH in pregnancy that reported the impact of different levels of control of blood pressure on the risk of PE or SGA. We completed a literature search through PubMed, Embase, Cinahl, Web of science, Cochrane CENTRAL Library Relative risks with random effect were calculated with their 95% confidence intervals (95%CI). RESULTS: Six trials including 495 participants provided data on blood pressure (BP) after entry to the study. Four studies compared antihypertensive agents to no treatment and two studies compared antihypertensive agents to placebo. All trials were conducted between 1976 and 1990 and were considered to be at high risk of bias. There was high heterogeneity between studies for mean arterial pressure (MAP) after randomization (I2 = 87%) and SGA (I2 = 60%), but not for PE (I2 = 0%). There were large differences between studies in the inclusion criteria, antihypertensive regimens, targets of therapy, and gestational age range at entry to the trials. In women receiving antihypertensive therapy, compared to those receiving placebo or no treatment, the MAP after entry to the trial was significantly lower (mean difference -4.2 mmHg, 95%CI -6.6 to -1.8; p = .006). However, there was no significant reduction in the risk of PE (relative risks (RR) 1.03, 95%CI 0.63-1.68; p = .90) or SGA (RR 1.01, 95%CI 0.35-2.93; p = .99). CONCLUSIONS: The findings of the meta-analysis suggest that lowering the blood pressure by antihypertensive medication in women with mild to moderate hypertension in the context of CH has no significant effect on the risk of SGA or PE. PMID- 28994337 TI - Aerosol therapy through high flow nasal cannula in pediatric patients. AB - INTRODUCTION: High flow nasal cannula (HFNC) is increasingly used in pediatric patients suffering from respiratory failure. In some disease processes, patients may also benefit from aerosol therapy. Therefore, the use of HFNC to deliver aerosolized medications is a convenient and attractive option. Areas covered: This review aims to appraise available evidence concerning the efficiency of aerosol nebulized therapy delivery using HFNC in pediatric patients. Expert commentary: Delivery of aerosol particles is a very complex process and depends on the use of oxygen vs. heliox, nebulizer type and position within the HFNC circuit, patient's breathing effort and pattern, and more importantly cannula size and flow rates. Current in vitro evidence suggests the amount of aerosol delivery is likely to be very low at high flows. Clinical studies are limited in pediatric patients and given the limited clinical data, it is not possible to make recommendations for or against aerosol delivery through HFNC for pediatric patients. PMID- 28994338 TI - A targeted graphene nanoplatform carrying histamine dihydrochloride for effective inhibition of leukemia-induced immunosuppression. AB - Despite the introduction of many efficient post-consolidation therapies for complete relapse in leukemia patients, many patients suffer from relapse. Reactive oxygen species (ROS) are considered an important parameter in the immunosuppression of acute myeloid leukemia, where they suppress the cytotoxic action of immune cells such as NK cells and T cells. This study demonstrates a way to achieve effective inhibition of immunosuppression by loading the drug histamine dihydrochloride (HDC) onto graphene quantum dots (GQDs) using hyaluronic acid as a targeting moiety for K-562 cells. The prepared GQD-based nanoplatform was stable and achieved high drug loading on the surface, which resulted in a sustained drug release profile over a period of time. Additionally, the drug-loaded graphene nanoplatform proved to be non-toxic at higher concentrations to K-562 cells and could be effectively taken up into cells due to the targeting moiety. In vitro ROS detection assays proved that the HDC loaded graphene nanoplatform could effectively inhibit ROS and thus prevent the immunosuppression caused by leukemic cells. PMID- 28994339 TI - Intranasal drug delivery devices and interventions associated with post-operative endoscopic sinus surgery. AB - This review article highlights the importance and advantages of the drug delivery systems applied via the nasal route after endoscopic sinus surgery (ESS) for patients suffering from chronic rhinosinusitis (CRS). After ESS, patients often require ongoing topical and systemic medication. To reduce the incidence of immediate and delayed post-surgical complications, a variety of temporary post operative nasal interventions are currently used. However, newly developed intranasal drug delivery devices can enhance tissue recovery after ESS by releasing therapeutic drugs locally, while providing structural support to reduce tissue adhesion and scaring. Intranasal drug delivery devices are promising next generation post-surgery devices, offering advantages for enhancing tissue recovery through release of loaded therapeutic drugs locally in a controlled manner over the required time-frame during post-operative healing. The mechanisms and effectiveness of these drug delivery systems initiate a new era in providing topical controlled drug delivery to the sinus tissue and can be a guide for the future development of specific effective therapies of preparations with other drugs that otherwise should be administered parenterally. Hence, further research is required to validate their efficacy. PMID- 28994340 TI - 3D plasmonic nanoarchitecture as an emerging biosensing platform. PMID- 28994341 TI - "A sweet smile": the modulatory role of emotion in how extrinsic factors influence taste evaluation. AB - It has recently been demonstrated that the reported tastes/flavours of food/beverages can be modulated by means of external visual and auditory stimuli such as typeface, shapes, and music. The present study was designed to assess the role of the emotional valence of the product-extrinsic stimuli in such crossmodal modulations of taste. Participants evaluated samples of mixed fruit juice whilst simultaneously being presented with auditory or visual stimuli having either positive or negative valence. The soundtracks had either been harmonised with consonant (positive valence) or dissonant (negative valence) musical intervals. The visual stimuli consisted of images of emotional faces from the International Affective Picture System (IAPS) with valence ratings matched to the soundtracks. Each juice sample was rated on two computer-based scales: One anchored with the words sour and sweet, while the other scale required hedonic ratings. Those participants who tasted the juice sample while presented with the positively valenced stimuli rated the juice as tasting sweeter compared to negatively valenced stimuli, regardless of whether the stimuli were visual or auditory. These results suggest that the emotional valence of food-extrinsic stimuli can play a role in shaping food flavour evaluation and liking. PMID- 28994342 TI - Malignant Ectomesenchymoma: Series Analysis of a Histologically and Genetically Heterogeneous Tumor. AB - AIMS: Malignant ectomesenchymoma is a rare pediatric neoplasm with dual mesenchymal and neuroectodermal elements. Mesenchymal component is usually rhabdomyosarcoma, particularly embryonal subtype, whereas neuroectodermal derivatives are frequently a neuroblastic tumor. Ectomesenchymoma manifests in various sites given the wide migration of neural crest cells during development, though the pelvis/perineum is most often involved. Moreover, no unique unifying molecular abnormality has been determined. METHODS: We conducted a retrospective study to analyze the spectrum of ectomesenchymal tumors encountered in our pediatric population. Six patients were identified and data pertaining to patients' demographic, tumor size and site, histologic components with immunophenotypic profile, molecular alterations, treatment, and outcome were collected. RESULTS: Mesenchymal elements, represented by rhabdomyosarcoma in all instances, were the dominant component in the majority of cases (5/6). Embryonal and alveolar morphology had similar distribution (3/6) and all patients with alveolar subtype harbored the characteristic translocations of this entity. The neuroectodermal component was most often a neuroblastic-like neoplasm (4/6); however, 2/6 cases demonstrated primitive neuroectodermal tumor-like morphology. No unifying alterations were found on molecular studies. CONCLUSIONS: Our analysis extends the histologic and molecular spectrum of these tumors and highlights their heterogeneity. The percentage of cases with alveolar rhabdomyosarcoma or primitive neuroectodermal-like tumor components suggests that these types of elements might be underreported. This study is also the first to demonstrate FOXO1 gene rearrangements in malignant ectomesenchymoma with alveolar rhabdomyosarcoma subtype. PMID- 28994343 TI - Radiotherapy plus rituximab as first-line regimen for localized follicular lymphoma. AB - Early-stage follicular lymphoma (FL) can be cured with involved-field radiotherapy (IF-RT); however, many patients relapse in non-irradiated areas. A combined association with chemotherapy could increase treatment efficacy, but toxic effects could be unacceptable. In vitro synergistic effect between rituximab (R) and RT has been observed, but clinical data are limited. We retrospectively analyzed 41 early-stage FL patients receiving R and IF-RT as first-line treatment. We administered R 375mg/m2 weekly for four courses, before or after IF-RT (median dose 24 Gy). Primary outcome was PFS, secondary endpoints were CR rate, OS and safety. All patients achieved CR, after a median follow-up of 46 months only three patients relapsed after 18, 26 and 42 months; estimated 5 year PFS was 90%. We suggest R in association with IF-RT could represent a feasible first-line treatment option for early-stage FL and could increase efficacy without additional toxicity compared to available data about RT alone. PMID- 28994344 TI - Phase-I randomized trial of doxorubicin hydrochloride liposome injection versus Caelyx(r) in multiple myeloma. PMID- 28994345 TI - Modelling period fertility: Schooling and intervals following a birth in Eastern Africa. AB - We describe a regression-based approach to the modelling of age-, order-, and duration-specific period fertility, using retrospective survey data. The approach produces results that are free of selection biases and can be used to study differential fertility. It is applied to Demographic and Health Survey data for Ethiopia, Kenya, Tanzania, and Zimbabwe to investigate differential trends in fertility by education. Parity progression fell and the intervals following each birth lengthened between the 1970s and 2000s in all four countries. Fertility fell most among women with secondary education. In contrast to other world regions, postponement of successive births for extended periods accounted for much of the initial drop in fertility in these African countries. However, family size limitation by women with secondary education in Ethiopia and Kenya and longer birth spacing in Zimbabwe also played significant roles. Thus, birth control is being adopted in Eastern Africa in response to diverse changes in fertility preferences. PMID- 28994346 TI - The factor structure of the Dispositional Hope Scale in hemiplegic stroke patients. AB - BACKGROUND: Hope is an important coping strategy and psychological resource for patients with a chronic illness. Stroke patients are exposed to stressful situations such as limited daily life activities, cognitive impairments and financial burdens. AIM: This study investigated the factor structure of the Dispositional Hope Scale (DHS) and verified its validity when examining stroke patients. METHODS: This methodological study used secondary, cross-sectional data analysis to investigate the factors related to participation restriction in chronic stroke patients. The DHS's reliability was assessed by calculating the internal consistency of Cronbach's alpha. The structure of the DHS was analyzed by confirmatory factor analysis. The one-factor model (Korean version), two factor model (original version) and bifactor models were compared. RESULTS: The fit indices provided evidence for the two-factor DHS model among hemiplegic stroke patients. Although the two-factor model was identified as superior by the Akaike information criterion value, both models had strong goodness-of-fit indices. The DHS had an adequate level of internal consistency in measuring hope in stroke patients. CONCLUSIONS: The DHS is a valid, reliable and useful tool for examining hemiplegic stroke patients. Identifying the psychometric properties of the DHS can help health professionals implement program development for stroke patients. PMID- 28994347 TI - Children's educational attainment, occupation, and income and their parents' mortality. AB - Using data from Finland, this paper contributes to a small but growing body of research regarding adult children's education, occupation, and income and their parents' mortality at ages 50+ in 1970-2007. Higher levels of children's education are associated with 30-36 per cent lower parental mortality at ages 50 75, controlling for parents' education, occupation, and income. This association is fully mediated by children's occupation and income, except for cancer mortality. Having at least one child educated in healthcare is associated with 11 16 per cent lower all-cause mortality at ages 50-75, an association that is largely driven by mortality from cardiovascular diseases. Children's higher white collar occupation and higher income is associated with 39-46 per cent lower mortality in the fully adjusted models. At ages 75+, these associations are much smaller overall and children's schooling remains more strongly associated with mortality than children's occupation or income. PMID- 28994349 TI - The therapeutic potential of a calorie-restricted ketogenic diet for the management of Leber hereditary optic neuropathy. AB - Leber hereditary optic neuropathy (LHON) is a maternally inherited, bilateral, sequential optic neuropathy that usually affects young males. LHON arises from a defect in complex I of the oxidative phosphorylation chain that generates increased reactive oxygen species and causes a decline in cellular ATP production. There exists no cure at present for LHON. Asymptomatic LHON mutation carriers show signs of increased mitochondrial biogenesis that may compensate for the compromise in complex I activity. Partial recovery in LHON is associated with a wider optic disc diameter and a younger age at disease onset, which may allow for greater mitochondrial bioenergetic capacity. Rescuing a mitochondrial bioenergetic deficit soon after disease onset may improve the chances of recovery and reduce visual loss in the second eye. We here propose that a calorie restricted ketogenic diet has the potential to enhance mitochondrial bioenergetic capacity and should be explored as a potential therapeutic option for treating LHON. PMID- 28994348 TI - From pathogenesis to novel therapies in the treatment of primary biliary cholangitis. AB - INTRODUCTION: Primary biliary cholangitis (PBC) is an immune-mediated liver disease characterized by chronic inflammation of the intrahepatic bile ducts, causing progressive ductopenia, cholestasis and fibrosis, and leading to liver failure. Ursodeoxycholic acid (UDCA) is the first-line therapy for the treatment of PBC patients. This is effective in majority of patients; however, up to 20 percent of patients have an incomplete response to UDCA therapy and have a reduced prognosis as compared to healthy individuals. Obeticholic acid (OCA) has been recently registered as second-line therapy for patients with incomplete response to UDCA, with plans to demonstrate the long-term clinical efficacy. Areas covered: Recent evolution in our understanding of disease mechanisms is leading to the advent of new and re-purposed therapeutic agents targeting key processes in the etiopathogenesis. Several therapeutic targets have been proposed which can be categorized into three compartments: immune, biliary and fibrosis. In this review we describe the main biological mechanisms underpinning disease development and progression in PBC and the new targeted therapies on the horizon. Expert commentary: Testing new drugs towards hard clinical endpoints is challenging in PBC due to its low prevalence and the slow progression of the disease. Novel promising biomarkers are under study and should be evaluated as surrogate endpoints in clinical trials. PMID- 28994350 TI - The validity of the MMPI-2/MMPI-2-RF Symptom Validity Scale (FBS/FBS-r) is established: reply to Nichols (2017). AB - We reply to Nichols' (2017) critique of our commentary on the MMPI-2/MMPI-2-RF Symptom Validity Scale (FBS/FBS-r) as a measure of symptom exaggeration versus a measure of litigation response syndrome (LRS). Nichols claims that we misrepresented the thrust of the original paper he co-authored with Gass; namely, that they did not represent that the FBS/FBS-r were measures of LRS but rather, intended to convey that the FBS/RBS-r were indeterminate as to whether the scales measured LRS or measured symptom exaggeration. Our original commentary offered statistical support from published literature that (1) FBS/FBS-r were associated with performance validity test (PVT) failure, establishing the scales as measures of symptom exaggeration, and (2) persons in litigation who passed PVTs did not produce clinically significant elevations on the scales, contradicting that FBS/FBS-r were measures of LRS. In the present commentary, we draw a distinction between the psychometric data we present supporting the validity of FBS/FBS-r, and the conceptual, non-statistical arguments presented by Nichols, who does not refute our original empirically based conclusions. PMID- 28994352 TI - The impact of a multi-level maternal health programme on facility delivery and capacity for emergency obstetric care in Zambia. AB - In 2012, Saving Mothers, Giving Life (SMGL), a multi-level health systems initiative, launched in Kalomo District, Zambia, to address persistent challenges in reducing maternal mortality. We assessed the impact of the programme from 2012 to 2013 using a quasi-experimental study with both household- and health facility level data collected before and after implementation in both intervention and comparison areas. A total of 21,680 women and 75 non-hospital health centres were included in the study. Using the difference-in-differences method, multivariate logistic regression, and run charts, rates of facility-based birth (FBB) and delivery with a skilled birth provider were compared between intervention and comparison sites. Facility capacity to provide emergency obstetric and newborn care was also assessed before and during implementation in both study areas. There was a 45% increase in the odds of FBB after the programme was implemented in Kalomo relative to comparison districts, but there was a limited measurable change in supply-side indicators of intrapartum maternity care. Most facility level changes related to an increase in capacity for newborn care. As SMGL and similar programmes are scaled-up and replicated, our results underscore the need to ensure that the health services supply is in balance with improved demand to achieve maximal reductions in maternal mortality. PMID- 28994354 TI - Monitoring and assessment of ingestive chewing sounds for prediction of herbage intake rate in grazing cattle. AB - Accurate measurement of herbage intake rate is critical to advance knowledge of the ecology of grazing ruminants. This experiment tested the integration of behavioral and acoustic measurements of chewing and biting to estimate herbage dry matter intake (DMI) in dairy cows offered micro-swards of contrasting plant structure. Micro-swards constructed with plastic pots were offered to three lactating Holstein cows (608+/-24.9 kg of BW) in individual grazing sessions (n=48). Treatments were a factorial combination of two forage species (alfalfa and fescue) and two plant heights (tall=25+/-3.8 cm and short=12+/-1.9 cm) and were offered on a gradient of increasing herbage mass (10 to 30 pots) and number of bites (~10 to 40 bites). During each grazing session, sounds of biting and chewing were recorded with a wireless microphone placed on the cows' foreheads and a digital video camera to allow synchronized audio and video recordings. Dry matter intake rate was higher in tall alfalfa than in the other three treatments (32+/-1.6 v. 19+/-1.2 g/min). A high proportion of jaw movements in every grazing session (23 to 36%) were compound jaw movements (chew-bites) that appeared to be a key component of chewing and biting efficiency and of the ability of cows to regulate intake rate. Dry matter intake was accurately predicted based on easily observable behavioral and acoustic variables. Chewing sound energy measured as energy flux density (EFD) was linearly related to DMI, with 74% of EFD variation explained by DMI. Total chewing EFD, number of chew-bites and plant height (tall v. short) were the most important predictors of DMI. The best model explained 91% of the variation in DMI with a coefficient of variation of 17%. Ingestive sounds integrate valuable information to remotely monitor feeding behavior and predict DMI in grazing cows. PMID- 28994355 TI - Treating depression with physical activity in adolescents and young adults: a systematic review and meta-analysis of randomised controlled trials. AB - We aimed to establish the treatment effect of physical activity for depression in young people through meta-analysis. Four databases were searched to September 2016 for randomised controlled trials of physical activity interventions for adolescents and young adults, 12-25 years, experiencing a diagnosis or threshold symptoms of depression. Random-effects meta-analysis was used to estimate the standardised mean difference (SMD) between physical activity and control conditions. Subgroup analysis and meta-regression investigated potential treatment effect modifiers. Acceptability was estimated using dropout. Trials were assessed against risk of bias domains and overall quality of evidence was assessed using GRADE criteria. Seventeen trials were eligible and 16 provided data from 771 participants showing a large effect of physical activity on depression symptoms compared to controls (SMD = -0.82, 95% CI = -1.02 to -0.61, p < 0.05, I2 = 38%). The effect remained robust in trials with clinical samples (k = 5, SMD = -0.72, 95% CI = -1.15 to -0.30), and in trials using attention/activity placebo controls (k = 7, SMD = -0.82, 95% CI = -1.05 to 0.59). Dropout was 11% across physical activity arms and equivalent in controls (k = 12, RD = -0.01, 95% CI = -0.04 to 0.03, p = 0.70). However, the quality of RCT-level evidence contributing to the primary analysis was downgraded two levels to LOW (trial-level risk of bias, suspected publication bias), suggesting uncertainty in the size of effect and caution in its interpretation. While physical activity appears to be a promising and acceptable intervention for adolescents and young adults experiencing depression, robust clinical effectiveness trials that minimise risk of bias are required to increase confidence in the current finding. The specific intervention characteristics required to improve depression remain unclear, however best candidates given current evidence may include, but are not limited to, supervised, aerobic-based activity of moderate-to-vigorous intensity, engaged in multiple times per week over eight or more weeks. Further research is needed. (Registration: PROSPERO-CRD 42015024388). PMID- 28994356 TI - Age modification of the relationship between C-reactive protein and fatigue: findings from Understanding Society (UKHLS). AB - BACKGROUND: Systemic inflammation may play a role in the development of idiopathic fatigue, that is, fatigue not explained by infections or diagnosed chronic illness, but this relationship has never been investigated in community studies including the entire adult age span. We examine the association of the inflammatory marker C-reactive protein (CRP) and fatigue assessed annually in a 3 year outcome period for UK adults aged 16-98. METHODS: Multilevel models were used to track fatigue 7, 19, and 31 months after CRP measurement, in 10 606 UK individuals. Models accounted for baseline fatigue, demographics, health conditions diagnosed at baseline and during follow-up, adiposity, and psychological distress. Sensitivity analyses considered factors including smoking, sub-clinical disease (blood pressure, anaemia, glycated haemoglobin), medications, ethnicity, and alcohol consumption. RESULTS: Fatigue and CRP increased with age, and women had higher values than men. CRP was associated with future self-reported fatigue, but only for the oldest participants. Thus, in those aged 61-98 years, high CRP (>3 mg/L) independently predicted greater fatigue 7, 19, and 31 months after CRP measurement [odds ratio for new-onset fatigue after 7 months: 1.88, 95% confidence interval (CI) 1.21-2.92; 19 months: 2.25, CI 1.46-3.49; 31 months: 1.65, CI 1.07-2.54]. No significant longitudinal associations were seen for younger participants. CONCLUSIONS: Our findings support previously described CRP-fatigue associations in older individuals. However, there are clear age modifications in these associations, which may reflect a contribution of unmeasured sub-clinical disease of limited relevance to younger individuals. Further work is necessary to clarify intervening processes linking CRP and fatigue in older individuals. PMID- 28994357 TI - The cross-national epidemiology of specific phobia in the World Mental Health Surveys - CORRIGENDUM. PMID- 28994358 TI - A qualitative study conducted in the USA exploring Latino fathers' beliefs, attitudes and practices related to their young children's eating, physical activity and sedentary behaviours. AB - OBJECTIVE: Increasing evidence documents fathers' influential role in their children's eating, physical activity (PA) and sedentary behaviours (SB). We aimed to expand limited existing research examining fathers' influence in these areas by exploring Latino fathers' beliefs, attitudes and practices related to eating, PA and SB of their young children. DESIGN: Seven focus group discussions were conducted in Spanish with Latino fathers (n 28) of children aged 2-8 years. Audio recordings were transcribed and translated verbatim without identifiers. Data were analysed using thematic analysis to identify key concepts and themes using NVivo 11 software. RESULTS: Fathers expressed positive beliefs and attitudes about the importance of healthy eating for their young children, themselves and their families. Nevertheless, the majority reported familial practices including eating out, getting take-out, etc. that have been linked to increased obesity risk among Latino children. Fathers were more involved and engaged in children's PA than eating and feeding. However, several fathers reported engaging predominantly in sedentary activities with their children, appeared permissive of children's sedentary habits and struggled to set limits on children's screen time. CONCLUSIONS: We provide new information on Latino fathers' beliefs and child feeding and PA practices that may provide important targets for interventions aimed at promoting healthful eating and PA behaviours of Latino children. Future research should further quantify the influence of Latino fathers' parenting styles and practices on development of children's eating, PA and SB. This information is needed to identify risk factors amenable to interventions and to design culturally appropriate parenting and family-based interventions targeting Latino children's home environment and designed to meet this ethnic group's specific needs. PMID- 28994359 TI - Weight resilience and fruit and vegetable intake among African-American women in an obesogenic environment. AB - OBJECTIVE: To investigate relationships between weight resilience (maintaining a normal weight in a food desert environment) and fruit and vegetable (F&V) intake, attitudes and barriers. DESIGN: Cross-sectional, in-person surveys collected May December 2011, including self-reported data on F&V-related psychosocial factors, attitudes and barriers. Two 24 h dietary recalls were completed; weight and height were measured. Multivariable regression models estimated prevalence ratios (95 % CI). SETTING: Two low-income, predominantly African-American food deserts in Pittsburgh, Pennsylvania, USA. SUBJECTS: Women aged 18-49 years (n 279) who were the primary food shopper in a household randomly selected for a parent study. RESULTS: Fifteen per cent were weight resilient, 30 % were overweight and 55 % were obese. Overall, 25 % reported eating >=5 F&V servings/d. After adjustment for age, education, parity, employment, living alone, physical activity, per capita income and mean daily energy intake, women eating >=5 F&V servings/d were 94 % more likely to be weight resilient compared with those eating <5 servings/d (1.94; 1.10, 3.43). Across BMI groups, self-efficacy regarding F&V consumption was high and few F&V barriers were reported. The most frequently reported barrier was concern about the cost of F&V (36 %). Of the attitudinal F&V-related factors, only concern about wasting food when serving F&V was associated with weight resilience in adjusted models (0.29; 0.09, 0.94). In a model predicting consuming >=5 F&V servings/d, driving one's own car to the store was the only attitudinal F&V-related factor associated with consumption (1.50; 1.00, 2.24). CONCLUSIONS: In this population, weight resilience may be encouraged by improving access to affordable and convenient F&V options and providing education on ways to make them palatable to the entire household, rather than by shifting women's F&V perceptions, which are already positive. PMID- 28994360 TI - Effects of childhood trauma on left inferior frontal gyrus function during response inhibition across psychotic disorders. AB - BACKGROUND: Childhood trauma is a risk factor for psychosis. Deficits in response inhibition are common to psychosis and trauma-exposed populations, and associated brain functions may be affected by trauma exposure in psychotic disorders. We aimed to identify the influence of trauma-exposure on brain activation and functional connectivity during a response inhibition task. METHODS: We used functional magnetic resonance imaging to examine brain function within regions-of interest [left and right inferior frontal gyrus (IFG), right dorsolateral prefrontal cortex, right supplementary motor area, right inferior parietal lobule and dorsal anterior cingulate cortex], during the performance of a Go/No-Go Flanker task, in 112 clinical cases with psychotic disorders and 53 healthy controls (HCs). Among the participants, 71 clinical cases and 21 HCs reported significant levels of childhood trauma exposure, while 41 clinical cases and 32 HCs did not. RESULTS: In the absence of effects on response inhibition performance, childhood trauma exposure was associated with increased activation in the left IFG, and increased connectivity between the left IFG seed region and the cerebellum and calcarine sulcus, in both cases and healthy individuals. There was no main effect of psychosis, and no trauma-by-psychosis interaction for any other region-of-interest. Within the clinical sample, the effects of trauma exposure on the left IFG activation were mediated by symptom severity. CONCLUSIONS: Trauma-related increases in activation of the left IFG were not associated with performance differences, or dependent on clinical diagnostic status; increased IFG functionality may represent a compensatory (overactivation) mechanism required to exert adequate inhibitory control of the motor response. PMID- 28994361 TI - Prediction of drug abuse recurrence: a Swedish National Study. AB - BACKGROUND: Relapse from drug abuse (DA) is common, but has rarely been studied in general population samples using a wide range of objective predictors. METHOD: Using nationwide registries, we ascertained 44 523 subjects first registered for DA between the ages of 15 and 40 in 1998 to 2004 and followed for 8 years. We predicted relapse in subjects defined as a second DA registration. We also predicted DA relapse in relative pairs concordant for DA but discordant for relapse. RESULTS: In multivariate regression analyses, the strongest predictors for relapse were prior criminal behavior, male sex, being on social welfare, low school achievement, prior alcoholism, and a high-risk father. A risk index trained from these analyses on random split-halves demonstrated a risk ratio of 1.11 [95% confidence intervals (CIs) 1.10-1.11] per decile and an ROC value of 0.70 (0.69-0.71). Co-relative analyses indicated that a modest proportion of this association was causal, with the remainder arising from familial confounders. A developmental structural equation model revealed a complex interviewing of risk pathways to DA with three key mediational hubs: low educational attainment, early age at first registration, and being on social welfare. CONCLUSIONS: In a general population sample, using objective registry information, DA relapse is substantially predictable. However, the identified risk factors may not be valid targets for interventions because many index familial risk and may not impact causally on probability of relapse. Risk for DA relapse may reflect an inter weaving, over developmental time, of genetic-temperamental vulnerability, indices of externalizing behaviors and social factors reflecting deprivation. PMID- 28994362 TI - Perceived Workplace Interpersonal Support Among Workers of the Fukushima Daiichi Nuclear Power Plants Following the 2011 Accident: The Fukushima Nuclear Energy Workers' Support (NEWS) Project Study. AB - OBJECTIVE: The 2011 Fukushima Daiichi nuclear accident was the worst nuclear disaster since Chernobyl. The Daiichi workers faced multiple stressors (workplace trauma, victim experiences, and public criticism deriving from their company's post-disaster management). Literatures suggest the importance of workplace interpersonal support (WIS) in enhancing psychological health among disaster workers. We sought to elucidate the role of their demographics, disaster-related experiences, and post-traumatic stress symptoms on perceived WIS. METHODS: We analyzed self-report questionnaires of 885 workers 2-3 months post-disaster. We used sociodemographic and disaster exposure-related variables and post-traumatic stress symptoms (measured by the Impact of Event Scale-Revised) as independent variables. We asked whether WIS from colleagues, supervisors, or subordinates was perceived as helpful, and used yes or no responses as a dependent variable. Logistic regression analyses were performed to assess correlates of WIS. RESULTS: Of the participants, one-third (34.7%) reported WIS. WIS was associated with younger age (20-28 years [vs 49-], adjusted odds ratio [aOR]: 3.25, 95% CI: 1.99 5.32), supervisory work status (aOR: 2.30, 95% CI: 1.35-3.92), and discrimination or slur experience (aOR: 1.65, 95% CI: 1.08-2.53). CONCLUSIONS: Educational programs focusing on WIS might be beneficial to promote psychological well-being among nuclear disaster workers, especially younger workers, supervisors, and workers with discrimination experiences. (Disaster Med Public Health Preparedness. 2018;12:460-463). PMID- 28994363 TI - Mass Casualty Triage in the Case of Carbon Monoxide Poisoning: Lessons Learned. AB - ABSTRACTCarbon monoxide (CO) can cause mass intoxication, but no standard triage algorithm specifically addresses CO poisoning. The roles of some recent diagnostic tools in triage as well as treatment with hyperbaric oxygen are controversial. We describe a mass casualty case of CO poisoning involving 77 patients, with a focus on the triage and treatment options decided on-site. The reasons for choosing these options are reviewed, and the pitfalls that occurred and the lessons learned from this major incident are described. We discuss the potential to improve the management of such an event and strategies to accomplish this, including simplifying triage and administering oxygen to all exposed persons for 6 h. (Disaster Med Public Health Preparedness. 2018; 12: 373-378). PMID- 28994364 TI - Comparison of the therapeutic effects and side effects of tadalafil and sildenafil after surgery in young infants with pulmonary arterial hypertension due to systemic-to-pulmonary shunts. AB - Young children with CHD and large systemic-to-pulmonary shunts eventually develop pulmonary hypertension. At present, phosphodiesterase type-5 inhibitors such as sildenafil have been used to control pulmonary pressure before and after cardiac surgery. Recently, tadalafil has been utilised in older children with similar efficacy, but it has been used to a lesser extent in young infants. From April, 2015 to June, 2016, 42 patients aged 3-24 months with a large septal defect and pulmonary arterial hypertension were randomly divided into two equal groups: one group received oral sildenafil (1-3 mg/kg/day every 8 hours), whereas the other group received oral tadalafil (1 mg/kg once a day) from 7-10 days before surgery to 3-4 weeks after surgery. During the first 48 hours after surgery, pulmonary artery-to-aortic pressure ratio and recorded systolic pulmonary artery pressures were not significantly different between the two groups (p>0.05); moreover, there were no differences in paediatric ICU length of stay, mechanical ventilation time, clinical findings of low cardiac output state, and echocardiographic data between the two groups (p>0.05). Most of the patients had no side effects, and only five patients had a minor with no significant difference in both groups (p=0.371). Tadalafil can be considered as an effective oral therapy for preoperative and postoperative pulmonary hypertension in young infants. It can be administered at a once-daily dose with an appropriate efficacy and safety profile as sildenafil, and therefore it can be considered as an alternative to sildenafil in young children. PMID- 28994365 TI - Cardiovascular pre-participation screening in young athletes: Recommendations of the Association of European Paediatric Cardiology - CORRIGENDUM. PMID- 28994366 TI - [Child abuse and neglect in France. Finally recognize its individual and societal impact]. PMID- 28994367 TI - [Tau and cognitive disorders: a role for T lymphocytes]. PMID- 28994368 TI - [Origin of human dendritic cell diversity]. PMID- 28994370 TI - [Clostridium difficile: the beauty and the beast]. PMID- 28994369 TI - [Motivation and apathy in Parkinson's disease: implication of dopaminergic D3 receptors]. PMID- 28994371 TI - [The neuronal keepers of our dreams identified: are they a target of Parkinson disease?] PMID- 28994372 TI - [Clarifying the role of RIPK3 and necroptosis in non-alcoholic steatohepatitis]. PMID- 28994373 TI - [Neurotrophic factors for motor neurons: an a la carte menu]. PMID- 28994374 TI - [The actin cytoskeleton goes retroviral]. PMID- 28994375 TI - [How is transcription reinitiation governed in measles virus?] PMID- 28994376 TI - [Spironolactone: a sleeping pill for HIV in T lymphocytes]. PMID- 28994377 TI - [The loss of SCRIB ignites the macrophages]. PMID- 28994378 TI - [Cancer immunotherapy via systemic RNA delivery to dendritic cells]. PMID- 28994379 TI - [Fibromodulin, an oxidative stress-sensitive proteoglycan, regulates the fibrogenic response to liver injury in mice]. PMID- 28994380 TI - [Infiltrated B cells promote pancreatic ductal adenocarcinoma]. PMID- 28994381 TI - [Microbiome-derived butyrate alleviates intestinal graft versus host reaction]. PMID- 28994382 TI - ? PMID- 28994383 TI - [The complement system: a double edge sword in tumor progression]. AB - The complement system is a key component of the innate immunity, playing a role in pathogen elimination and in host homeostasis. The complement system has been considered for long time as an anti-tumoral element. However, recent studies showed a pro-tumoral effect of complement and particularly of the anaphylatoxines C3a and C5a in a large variety of tumor types. Complement proteins act on different levels of tumor progression, affecting the tumor cells, the angiogenesis and the immune microenvironment. The impact of the complement system on tumor progression seems to be cancer type-dependent and this has to be taken into account in the establishment of potential biomarkers and development of therapeutic strategies. PMID- 28994384 TI - [Follicular helper T cells and HIV - United for better and worse]. AB - Follicular helper T cells (Tfh) have been discovered in lymph nodes and, since then, are the focus of very intensive research to understand their origin, differentiation and functions. Tfh interact with B cells in the secondary lymphoid organs leading to B cell differentiation and maturation. Tfh are particularly studied in pathological contexts such as autoimmune diseases and infection by the human immunodeficiency virus (HIV). In the context of HIV infection, broadly neutralizing antibodies have been identified in a few patients. The generation of these broadly neutralizing antibodies requires a long and complex maturation of B cells in the secondary lymphoid organs. Characterizing Tfh functions and the relation with the quality of antibodies in HIV infection might help in designing novel immunotherapies and vaccination strategies to induce broadly neutralizing antibodies. PMID- 28994385 TI - [Physical rehabilitation, train the brain!] AB - Since centuries, scientists, clinicians and philosophers have been debating about the interactions between the body and the mind. Researches and advances in neurophysiology over the last decades have challenged many principles and theories, mainly based on empirical observations, generally well accepted in clinical practice. These new findings, achieved through functional "magnetic resonance imaging", awake brain surgery and allow new techniques and opportunities in physical rehabilitation. More than ever the body and the brain must be considered and treated as a functional entity, the distinction between body and soul developed by Platon should no longer be applied. The development of new technologies, in particular the virtual reality, lends itself perfectly to this global approach. The aim of this article is to present how a purely cognitive training can have beneficial effects on the body and the motor performances in clinics. PMID- 28994386 TI - [Integrating clinical research into epidemic response: the field perspective in the Ebola experience]. AB - During the 2013-2016 west African Ebola outbreak that affected West Africa, accelerated clinical trials, testing unproven but promising and potentially lifesaving experimental interventions emerged as a key component of the global outbreak. In 2017, no Ebola medical countermeasures had proven antiviral efficacy in patients. However, in September 2014, the World Health Organization inventoried a list of potential drug candidates developed or repurposed with demonstrated antiviral efficacy in vitro or in animal models. Numerous therapeutics were considered or explored during the outbreak, including nucleoside and nucleotide analogues, nucleic acid-based drugs and immunotherapeutics. Drugs in clinical trials were tested within the framework of optimized supportive care with fluids and electrolytes and management of severe compromise of multiple organs resulting from viral cytopathology and immune mediated cell damage. Assessment of those therapeutics with encouraging preliminary efficacy or safety profile, like the repurposed direct antiviral agent favipiravir or the combination of antibodies ZMapp requires further investigation to confirm their efficacy in humans, propose appropriate doses and evaluate the possibility of treatment combinations. During the lull before the next epidemic, major challenges for managing future Ebola epidemics include scientific, clinical and public health preparedness with establishment of innovative patient care and clinical research support in remote poor areas where Ebola and other deadly infectious diseases typically reemerge. PMID- 28994387 TI - [The identity of normal and cancer stem cells]. AB - What is a stem cell? Is stemness an intrinsic or extrinsic property? What role does the microenvironment play in the stemness identity? We distinguish four identities for normal and cancerous stem cells and explore their consequences for therapeutic strategy choice in the oncology setting. Acquisition of genetic and epigenetic alterations during cell transformation and disease progression questions the stability of the stemness property's identity in cancers. PMID- 28994388 TI - [Cancer: three eras of personalized medicine]. AB - Since the completion of the first human DNA sequence, genomic approaches have penetrated into cancer research and therapy: first through expression profiling for diagnostic, prognostic and predictive purposes, then by sequencing of tumour DNA in order to define and apply targeted therapies. These overlapping changes occurred quite rapidly and are now overshadowed by immuno-oncology approaches that show much promise. There is however still much left to understand to make this more widely applicable, and the extreme cost of these therapies is a serious concern. PMID- 28994389 TI - Molecular architecture underlying fluid absorption by the developing inner ear. AB - Mutations of SLC26A4 are a common cause of hearing loss associated with enlargement of the endolymphatic sac (EES). Slc26a4 expression in the developing mouse endolymphatic sac is required for acquisition of normal inner ear structure and function. Here, we show that the mouse endolymphatic sac absorbs fluid in an SLC26A4-dependent fashion. Fluid absorption was sensitive to ouabain and gadolinium but insensitive to benzamil, bafilomycin and S3226. Single-cell RNA seq analysis of pre- and postnatal endolymphatic sacs demonstrates two types of differentiated cells. Early ribosome-rich cells (RRCs) have a transcriptomic signature suggesting expression and secretion of extracellular proteins, while mature RRCs express genes implicated in innate immunity. The transcriptomic signature of mitochondria-rich cells (MRCs) indicates that they mediate vectorial ion transport. We propose a molecular mechanism for resorption of NaCl by MRCs during development, and conclude that disruption of this mechanism is the root cause of hearing loss associated with EES. PMID- 28994390 TI - Clearance of beta-amyloid is facilitated by apolipoprotein E and circulating high density lipoproteins in bioengineered human vessels. AB - Amyloid plaques, consisting of deposited beta-amyloid (Abeta), are a neuropathological hallmark of Alzheimer's Disease (AD). Cerebral vessels play a major role in AD, as Abeta is cleared from the brain by pathways involving the cerebrovasculature, most AD patients have cerebrovascular amyloid (cerebral amyloid angiopathy (CAA), and cardiovascular risk factors increase dementia risk. Here we present a notable advance in vascular tissue engineering by generating the first functional 3-dimensioinal model of CAA in bioengineered human vessels. We show that lipoproteins including brain (apoE) and circulating (high-density lipoprotein, HDL) synergize to facilitate Abeta transport across bioengineered human cerebral vessels. These lipoproteins facilitate Abeta42 transport more efficiently than Abeta40, consistent with Abeta40 being the primary species that accumulates in CAA. Moreover, apoE4 is less effective than apoE2 in promoting Abeta transport, also consistent with the well-established role of apoE4 in Abeta deposition in AD. PMID- 28994392 TI - Building a better blood-brain barrier. AB - A new three-dimensional model of the blood-brain barrier can be used to study processes that are involved in neurodegenerative diseases. PMID- 28994393 TI - Quantitative measurement of HCV core antigen for management of interferon-free therapy in HCV-infected patients. AB - BACKGROUND: According to current recommendations diagnosis and management of HCV infection need detection and quantification of nucleic acids. In the era of direct-acting antivirals (DAA) it is essential to develop an inexpensive and simple method replacing polymerase chain reaction. Since there is no available data on HCV core antigen (HCVcAg) versus HCV RNA kinetics in the early phase of treatment with DAA, we carried out this study to evaluate the possible application of HCVcAg quantitative measurement for management of HCV infection. METHODS: 33 patients with HCV infection were enrolled and treated with either ombitasvir/paritaprevir/ritonavir +/- dasabuvir +/- ribavirin (OBV/PRV/r+/-DSV+/ RBV) or ledipasvir/sofosbuvir (LDV/SOF). Samples for quantitative HCV RNA and HCVcAg measurement were collected at the baseline, after 1, 7, 28 days and at the end of treatment, and then after 12 and 24 weeks of post-treatment follow-up. RESULTS: There was positive correlation between HCVcAg and HCV RNA levels at the baseline and after 1 day of treatment. Mean HCVcAg concentration declined faster than HCV RNA levels during the treatment phase. At week 4 HCV RNA was undetectable in 24, whereas HCVcAg in 28 patients. At the end of treatment and after 12 weeks of follow-up all patients were undetectable for both HCV RNA and HCVcAg. CONCLUSIONS: HCVcAg concentration and its early on-treatment testing can predict virological response. Simple testing procedures and significantly lower cost compared to HCV RNA testing support possible replacement of the viral load measurement in management of the majority of HCV-infected patients. PMID- 28994391 TI - A viral protein promotes host SAMS1 activity and ethylene production for the benefit of virus infection. AB - Ethylene plays critical roles in plant development and biotic stress response, but the mechanism of ethylene in host antiviral response remains unclear. Here, we report that Rice dwarf virus (RDV) triggers ethylene production by stimulating the activity of S-adenosyl-L-methionine synthetase (SAMS), a key component of the ethylene synthesis pathway, resulting in elevated susceptibility to RDV. RDV encoded Pns11 protein specifically interacted with OsSAMS1 to enhance its enzymatic activity, leading to higher ethylene levels in both RDV-infected and Pns11-overexpressing rice. Consistent with a counter-defense role for ethylene, Pns11-overexpressing rice, as well as those overexpressing OsSAMS1, were substantially more susceptible to RDV infection, and a similar effect was observed in rice plants treated with an ethylene precursor. Conversely, OsSAMS1 knockout mutants, as well as an osein2 mutant defective in ethylene signaling, resisted RDV infection more robustly. Our findings uncover a novel mechanism which RDV manipulates ethylene biosynthesis in the host plants to achieve efficient infection. PMID- 28994394 TI - Controlling the crack formation in inkjet-printed silver nanoparticle thin-films for high resolution patterning using intense pulsed light treatment. AB - During the last years, intense pulsed light (IPL) processing has been employed and studied intensively for the drying and sintering of metal nanoparticle layers deposited by means of printing methods on flexible polymer substrates. IPL was found to be a very fast and substrate-gentle approach qualified for the field of flexible and large-area printed electronics, i.e. manufactured via roll-to-roll processing. In this contribution, IPL is used for the fine-patterning of printed silver nanoparticle layers. The patterning is obtained by induced and controlled crack formation in the thin silver layer due to the intense exposure of IPL. The crack formation is controlled by selection of the substrate material, the fine tuning of the morphology of the silver layer and an application of a dielectric layer on top of the silver layer that acts as a stress concentrator. Careful optimization of the IPL parameters allowed to adjust the lateral width of the crack. This novel approach turned out to be a fast and reproducible high resolution patterning process for multiple applications, e.g. to pattern the source-drain electrodes for all-inkjet-printed thin-film transistors. PMID- 28994395 TI - In situ biasing and off-axis electron holography of a ZnO nanowire. AB - Quantitative characterization of electrically active dopants and surface charges in nano-objects is challenging, since most characterization techniques using electrons [1-3], ions [4] or field ionization effects [5-7] study the chemical presence of dopants, which are not necessarily electrically active. We perform cathodoluminescence and voltage contrast experiments on a contacted and biased ZnO nanowire with a Schottky contact and measure the depletion length as a function of reverse bias. We compare these results with state-of-the-art off-axis electron holography in combination with electrical in situ biasing on the same nanowire. The extension of the depletion length under bias observed in scanning electron microscopy based techniques is unusual as it follows a linear rather than square root dependence, and is therefore difficult to model by bulk equations or finite element simulations. In contrast, the analysis of the axial depletion length observed by holography may be compared with three-dimensional simulations, which allows estimating an n-doping level of 1 * 1018 cm-3 and negative sidewall surface charge of 2.5 * 1012 cm-2 of the nanowire, resulting in a radial surface depletion to a depth of 36 nm. We found excellent agreement between the simulated diameter of the undepleted core and the active thickness observed in the experimental data. By combining TEM holography experiments and finite element simulation of the NW electrostatics, the bulk-like character of the nanowire core is revealed. PMID- 28994396 TI - Analysis of noise generation and electric conduction at grain boundaries in CVD grown MoS2 field effect transistors. AB - Grain boundaries in a chemical vapour deposition (CVD)-grown monolayer of MoS2 induce significant effects on the electrical and low frequency noise characteristics of the MoS2. Here, we investigated the electrical properties and noise characteristics of MoS2 field effect transistors (FETs) made with CVD-grown monolayer MoS2. The electrical and noise characteristics of MoS2 FETs were analysed and compared for the MoS2 channel layers with and without grain boundaries. The grain boundary in the CVD-grown MoS2 FETs can be the dominant noise source, and dependence of the extracted Hooge parameters on the gate voltage indicated the domination of the correlated number-mobility fluctuation at the grain boundaries. The percolative noise characteristics of the single grain regions of MoS2 were concealed by the noise generated at the grain boundary. This study can enhance understanding of the electrical transport hindrance and significant noise generation by trapped charges at grain boundaries of the CVD grown MoS2 devices. PMID- 28994397 TI - Light scattering and random lasing in aqueous suspensions of hexagonal boron nitride nanoflakes. AB - Liquid phase exfoliation allows large scale production of 2D materials in solution. The particles are highly anisotropic and strongly scatter light. While spherical particles can be accurately and precisely described by a single parameter-the radius, 2D nanoflakes, however, cannot be so easily described. We investigate light scattering in aqueous solutions of 2D hexagonal boron nitride nanoflakes in the single and multiple scattering regimes. In the single scattering regime, the anisotropic 2D materials show a much stronger depolarization of light when compared to spherical particles of similar size. In the multiple scattering regime, the scattering as a function of optical path for hexagonal boron nitride nanoflakes of a given lateral length was found to be qualitatively equivalent to scattering from spheres with the same diameter. We also report the presence of random lasing in high concentration suspensions of aqueous h-BN mixed with Rhodamine B dye. The h-BN works as a scattering agent and Rhodamine B as a gain medium for the process. We observed random lasing at 587 nm with a threshold energy of 0.8 mJ. PMID- 28994398 TI - Highly sensitive and flexible strain sensors based on patterned ITO nanoparticle channels. AB - We demonstrate a highly sensitive and flexible bending strain sensor using tin doped indium oxide (ITO) nanoparticles (NPs) assembled in line patterns on flexible substrates. By utilizing transparent ITO NPs without any surface modifications, we could produce strain sensors with adjustable gauge factors and optical transparency. We were able to control the dimensional and electrical properties of the sensors, such as channel height and resistance, by controlling the NP assembly speed. Furthermore, we were able to generate controlled gauge factor with values ranging from 18 to 157, which are higher than previous cases using metallic Cr NPs and Au NPs. The alignment of the ITO NPs in parallel lines resulted in low crosstalk between the transverse and longitudinal bending directions. Finally, our sensor showed high optical transmittance, up to ~93% at 500 nm wavelength, which is desirable for flexible electronic applications. PMID- 28994399 TI - Contaminant deposition building shielding factors for US residential structures. AB - This paper presents validated building shielding factors designed for contemporary US housing-stock under an idealized, yet realistic, exposure scenario from contaminant deposition on the roof and surrounding surfaces. The building shielding factors are intended for use in emergency planning and level three probabilistic risk assessments for a variety of postulated radiological events in which a realistic assessment is necessary to better understand the potential risks for accident mitigation and emergency response planning. Factors are calculated from detailed computational housing-units models using the general purpose Monte Carlo N-Particle computational code, MCNP5, and are benchmarked from a series of narrow- and broad-beam measurements analyzing the shielding effectiveness of ten common general-purpose construction materials and ten shielding models representing the primary weather barriers (walls and roofs) of likely US housing-stock. Each model was designed to scale based on common residential construction practices and include, to the extent practical, all structurally significant components important for shielding against ionizing radiation. Calculations were performed for floor-specific locations from contaminant deposition on the roof and surrounding ground as well as for computing a weighted-average representative building shielding factor for single- and multi-story detached homes, both with and without basement as well for single wide manufactured housing-unit. PMID- 28994400 TI - Quasielastic and low-energy inelastic neutron scattering study of HoCrO3 by high resolution time-of-flight neutron spectroscopy. AB - n order to understand the origin of the huge quasielastic magnetic scattering observed previously with a back-scattering neutron spectrometer we have re-investigated the low energy excitations in HoCrO$_3$ by inelastic neutron scattering in a much wider energy range with time-of flight neutron spectrometers. The inelastic signals are due to the excitations between the ground state doublet of the Ho ion. The quasielastic signal is due to the fluctuation of the disordered Ho moments. At low temperature the intensity of quasielastic scattering is small. It starts increasing as the temperature increases above 30 K. At the same temperature the elastic intensity due to Ho moment ordering decreases in a similar way. This observation strengthens the hypothesis that the quasielastic scattering is due the fluctuations of the disordered Ho moments. The time scale of fluctuations has been determine from the quasielastic scattering and was found to vary from about 22 ps at T = 70 K to about 2.5 ps at T = 160 K. The stretched exponential line shape indicates a distribution of decay rates at low temperatures. PMID- 28994401 TI - Crystal structure of type II NADH:quinone oxidoreductase from Caldalkalibacillus thermarum with an improved resolution of 2.15 A. AB - Type II NADH:quinone oxidoreductase (NDH-2) is a respiratory enzyme found in the electron-transport chain of many species, with the exception of mammals. It is a 40-70 kDa single-subunit monotopic membrane protein that catalyses the oxidation of NADH and the reduction of quinone molecules via the cofactor FAD. NDH-2 is a promising new target for drug development given its essential role in many bacterial species and intracellular parasites. Only two bacterial NDH-2 structures have been reported and these structures are at moderate resolution (2.3-2.5 A). In this communication, a new crystallization platform is reported that produced high-quality NDH-2 crystals that diffracted to high resolution (2.15 A). The high-resolution NDH-2 structure was used for in silico quinone substrate-docking studies to investigate the binding poses of menadione and ubiquinone molecules. These studies revealed that a very limited number of molecular interactions occur at the quinone-binding site of NDH-2. Given that the conformation of the active site is well defined, this high-resolution structure is potentially suitable for in silico inhibitor-compound screening and ligand docking applications. PMID- 28994402 TI - Crystal structure of the starch-binding domain of glucoamylase from Aspergillus niger. AB - Glucoamylases are widely used commercially to produce glucose syrup from starch. The starch-binding domain (SBD) of glucoamylase from Aspergillus niger is a small globular protein containing a disulfide bond. The structure of A. niger SBD has been determined by NMR, but the conformation surrounding the disulfide bond was unclear. Therefore, X-ray crystal structural analysis was used to attempt to clarify the conformation of this region. The SBD was purified from an Escherichia coli-based expression system and crystallized at 293 K. The initial phase was determined by the molecular-replacement method, and the asymmetric unit of the crystal contained four protomers, two of which were related by a noncrystallographic twofold axis. Finally, the structure was solved at 2.0 A resolution. The SBD consisted of seven beta-strands and eight loops, and the conformation surrounding the disulfide bond was determined from a clear electron density map. Comparison of X-ray- and NMR-determined structures of the free SBD showed no significant difference in the conformation of each beta-strand, but the conformations of the loops containing the disulfide bond and the L5 loop were different. In particular, the difference in the position of the Calpha atom of Cys509 between the X-ray- and NMR-determined structures was 13.3 A. In addition, the B factors of the amino-acid residues surrounding the disulfide bond are higher than those of other residues. Therefore, the conformation surrounding the disulfide bond is suggested to be highly flexible. PMID- 28994403 TI - Large-scale crystallization and neutron crystallographic analysis of HSP70 in complex with ADP. AB - HSP70 belongs to the heat-shock protein family and binds to unfolded proteins, driven by ATP hydrolysis, in order to prevent aggregation. Previous X-ray crystallographic analyses of HSP70 have shown that HSP70 binds to ADP with internal water molecules. In order to elucidate the role of the water molecules, including their H/D atoms, a neutron diffraction study of the human HSP70 ATPase domain was initiated. Deuterated large crystals of the HSP-ADP complex (1.2-1.8 mm3) were successfully grown by large-scale crystallization, and a neutron diffraction experiment at BIODIFF resulted in diffraction to a maximum resolution of 2.2 A. After data reduction, the overall completeness, Rmeas and average I/sigma(I) were 90.4%, 11.7% and 8.1, respectively, indicating that the data set was sufficient to visualize H and D atoms. PMID- 28994404 TI - Identification, biochemical characterization and crystallization of the central region of human ATG16L1. AB - ATG16L1 plays a major role in autophagy. It acts as a molecular scaffold which mediates protein-protein interactions essential for autophagosome formation. The ATG12~ATG5-ATG16L1 complex is one of the key complexes involved in autophagosome formation. Human ATG16L1 comprises 607 amino acids with three functional domains named ATG5BD, CCD and WD40, where the C-terminal WD40 domain represents approximately 50% of the full-length protein. Previously, structures of the C terminal WD40 domain of human ATG16L1 as well as of human ATG12~ATG5 in complex with the ATG5BD of ATG16L1 have been reported. However, apart from the ATG5BD, no structural information for the N-terminal half, including the CCD, of human ATG16L1 is available. In this study, the authors aimed to structurally characterize the N-terminal half of ATG16L1. ATG16L111-307 in complex with ATG5 has been purified and crystallized in two crystal forms. However, both crystal structures revealed degradation of ATG16L1, resulting in crystals comprising only full-length ATG5 and the ATG5BD of ATG16L1. The structures of ATG5-ATG5BD in two novel crystal forms are presented, further supporting the previously observed dimerization of ATG5-ATG16L1. The reported degradation points towards a high instability at the linker region between the ATG5BD and the CCD in ATG16L1. Based on this observation and further biochemical analysis of ATG16L1, a stable 236 amino-acid subfragment comprising residues 72-307 of the N-terminal half of ATG16L1, covering the residual, so far structurally uncharacterized region of human ATG16L1, was identified. Here, the identification, purification, biochemical characterization and crystallization of the proteolytically stable ATG16L172-307 subfragment are reported. PMID- 28994405 TI - Crystallization and X-ray analysis of 23 nm virus-like particles from Norovirus Chiba strain. AB - Norovirus is a major causative pathogen of nonbacterial acute gastroenteritis. Despite the sequence similarity among various strains, noroviruses of different genotypes show different antigenicities and different binding profiles to histo blood group antigens (HBGAs). To reveal the relationships between the structure of the capsid and the diversity in antigenicity and the HBGA-binding profile, virus-like particles (VLPs) of the Chiba strain that belongs to genogroup I, genotype 4 were crystallized for X-ray structural analysis. Diffraction data were collected and processed at 3.2 A resolution. The crystal belonged to space group I222, with unit-cell parameters a = 290.0, b = 310.4 c = 350.4 A. The possible packing model indicated that the diameter of the particle was 280 A, which was much smaller than the 38 nm VLPs of Norovirus Norwalk strain (NV) with T = 3 icosahedral symmetry and composed of 180 VP1 proteins. The structure was solved by molecular replacement using the structure of the VP1 pentamer of NV 38 nm VLPs as a search model, revealing that the VLPs were smaller particles: 23 nm VLPs with T = 1 icosahedral symmetry, the structure of which has not yet been analyzed at high resolution. The structure of 23 nm VLPs will enable the two different VLPs of Norovirus to be compared, which will provide important information for understanding the structural basis of capsid formation. PMID- 28994406 TI - Crystallization via tubing microfluidics permits both in situ and ex situ X-ray diffraction. AB - A microfluidic platform was used to address the problems of obtaining diffraction quality crystals and crystal handling during transfer to the X-ray diffractometer. Crystallization conditions of a protein of pharmaceutical interest were optimized and X-ray data were collected both in situ and ex situ. PMID- 28994407 TI - Structure, activity and thermostability investigations of OXA-163, OXA-181 and OXA-245 using biochemical analysis, crystal structures and differential scanning calorimetry analysis. AB - The first crystal structures of the class D beta-lactamases OXA-181 and OXA-245 were determined to 2.05 and 2.20 A resolution, respectively; in addition, the structure of a new crystal form of OXA-163 was resolved to 2.07 A resolution. All of these enzymes are OXA-48-like and have been isolated from different clinical Klebsiella pneumoniae strains and also from other human pathogens such as Pseudomonas aeruginosa and Escherichia coli. Here, enzyme kinetics and thermostability studies are presented, and the new crystal structures are used to explain the observed variations. OXA-245 had the highest melting point (Tm = 55.8 degrees C), as determined by differential scanning calorimetry, compared with OXA 163 (Tm = 49.4 degrees C) and OXA-181 (Tm = 52.6 degrees C). The differences could be explained by the loss of two salt bridges in OXA-163, and an overall decrease in the polarity of the surface of OXA-181 compared with OXA-245. PMID- 28994408 TI - Conformational dynamics of the essential sensor histidine kinase WalK. AB - Two-component systems (TCSs) are key elements in bacterial signal transduction in response to environmental stresses. TCSs generally consist of sensor histidine kinases (SKs) and their cognate response regulators (RRs). Many SKs exhibit autokinase, phosphoryltransferase and phosphatase activities, which regulate RR activity through a phosphorylation and dephosphorylation cycle. However, how SKs perform different enzymatic activities is poorly understood. Here, several crystal structures of the minimal catalytic region of WalK, an essential SK from Lactobacillus plantarum that shares 60% sequence identity with its homologue VicK from Streptococcus mutans, are presented. WalK adopts an asymmetrical closed structure in the presence of ATP or ADP, in which one of the CA domains is positioned close to the DHp domain, thus leading both the beta- and gamma phosphates of ATP/ADP to form hydrogen bonds to the E- but not the delta-nitrogen of the phosphorylatable histidine in the DHp domain. In addition, the DHp domain in the ATP/ADP-bound state has a 25.7 degrees asymmetrical helical bending coordinated with the repositioning of the CA domain; these processes are mutually exclusive and alternate in response to helicity changes that are possibly regulated by upstream signals. In the absence of ATP or ADP, however, WalK adopts a completely symmetric open structure with its DHp domain centred between two outward-reaching CA domains. In summary, these structures of WalK reveal the intrinsic dynamic properties of an SK structure as a molecular basis for multifunctionality. PMID- 28994409 TI - Introducing site-specific cysteines into nanobodies for mercury labelling allows de novo phasing of their crystal structures. AB - The generation of high-quality protein crystals and the loss of phase information during an X-ray crystallography diffraction experiment represent the major bottlenecks in the determination of novel protein structures. A generic method for introducing Hg atoms into any crystal independent of the presence of free cysteines in the target protein could considerably facilitate the process of obtaining unbiased experimental phases. Nanobodies (single-domain antibodies) have recently been shown to promote the crystallization and structure determination of flexible proteins and complexes. To extend the usability of nanobodies for crystallographic work, variants of the Nb36 nanobody with a single free cysteine at one of four framework-residue positions were developed. These cysteines could be labelled with fluorophores or Hg. For one cysteine variant (Nb36-C85) two nanobody structures were experimentally phased using single wavelength anomalous dispersion (SAD) and single isomorphous replacement with anomalous signal (SIRAS), taking advantage of radiation-induced changes in Cys-Hg bonding. Importantly, Hg labelling influenced neither the interaction of Nb36 with its antigen complement C5 nor its structure. The results suggest that Cys-Hg labelled nanobodies may become efficient tools for obtaining de novo phase information during the structure determination of nanobody-protein complexes. PMID- 28994410 TI - Structure of the conserved Francisella virulence protein FvfA. AB - Francisella tularensis is a potent human pathogen that invades and survives in macrophage and epithelial cells. Two identical proteins, FTT_0924 from F. tularensis subsp. tularensis and FTL_1286 from F. tularensis subsp. holarctica LVS, have previously been identified as playing a role in protection of the bacteria from osmotic shock and its survival in macrophages. FTT_0924 has been shown to localize to the inner membrane, with its C-terminus exposed to the periplasm. Here, crystal structures of the F. novicida homologue FTN_0802, which we call FvfA, in two crystal forms are reported at 1.8 A resolution. FvfA differs from FTT_0924 and FTL_1286 by a single amino acid. FvfA has a DUF1471 fold that closely resembles the Escherichia coli outer membrane lipoprotein RscF, a component of a phosphorelay pathway involved in protecting bacteria from outer membrane perturbation. The structural and functional similarities and differences between these proteins and their implications for F. tularensis pathogenesis are discussed. PMID- 28994411 TI - X-ray and EM structures of a natively glycosylated HIV-1 envelope trimer. AB - The structural and biochemical characterization of broadly neutralizing anti-HIV 1 antibodies (bNAbs) has been essential in guiding the design of potential vaccines to prevent infection by HIV-1. While these studies have revealed critical mechanisms by which bNAbs recognize and/or accommodate N-glycans on the trimeric envelope glycoprotein (Env), they have been limited to the visualization of high-mannose glycan forms only, since heterogeneity introduced from the presence of complex glycans makes it difficult to obtain high-resolution structures. 3.5 and 3.9 A resolution crystal structures of the HIV-1 Env trimer with fully processed and native glycosylation were solved, revealing a glycan shield of high-mannose and complex-type N-glycans that were used to define the complete epitopes of two bNAbs. Here, the refinement of the N-glycans in the crystal structures is discussed and comparisons are made with glycan densities in glycosylated Env structures derived by single-particle cryo-electron microscopy. PMID- 28994412 TI - Towards a compact and precise sample holder for macromolecular crystallography. AB - Most of the sample holders currently used in macromolecular crystallography offer limited storage density and poor initial crystal-positioning precision upon mounting on a goniometer. This has now become a limiting factor at high throughput beamlines, where data collection can be performed in a matter of seconds. Furthermore, this lack of precision limits the potential benefits emerging from automated harvesting systems that could provide crystal-position information which would further enhance alignment at beamlines. This situation provided the motivation for the development of a compact and precise sample holder with corresponding pucks, handling tools and robotic transfer protocols. The development process included four main phases: design, prototype manufacture, testing with a robotic sample changer and validation under real conditions on a beamline. Two sample-holder designs are proposed: NewPin and miniSPINE. They share the same robot gripper and allow the storage of 36 sample holders in uni puck footprint-style pucks, which represents 252 samples in a dry-shipping dewar commonly used in the field. The pucks are identified with human- and machine readable codes, as well as with radio-frequency identification (RFID) tags. NewPin offers a crystal-repositioning precision of up to 10 um but requires a specific goniometer socket. The storage density could reach 64 samples using a special puck designed for fully robotic handling. miniSPINE is less precise but uses a goniometer mount compatible with the current SPINE standard. miniSPINE is proposed for the first implementation of the new standard, since it is easier to integrate at beamlines. An upgraded version of the SPINE sample holder with a corresponding puck named SPINEplus is also proposed in order to offer a homogenous and interoperable system. The project involved several European synchrotrons and industrial companies in the fields of consumables and sample changer robotics. Manual handling of miniSPINE was tested at different institutes using evaluation kits, and pilot beamlines are being equipped with compatible robotics for large-scale evaluation. A companion paper describes a new sample changer FlexED8 (Papp et al., 2017, Acta Cryst., D73, 841-851). PMID- 28994413 TI - FlexED8: the first member of a fast and flexible sample-changer family for macromolecular crystallography. AB - Automated sample changers are now standard equipment for modern macromolecular crystallography synchrotron beamlines. Nevertheless, most are only compatible with a single type of sample holder and puck. Recent work aimed at reducing sample-handling efforts and crystal-alignment times at beamlines has resulted in a new generation of compact and precise sample holders for cryocrystallography: miniSPINE and NewPin [see the companion paper by Papp et al. (2017, Acta Cryst., D73, 829-840)]. With full data collection now possible within seconds at most advanced beamlines, and future fourth-generation synchrotron sources promising to extract data in a few tens of milliseconds, the time taken to mount and centre a sample is rate-limiting. In this context, a versatile and fast sample changer, FlexED8, has been developed that is compatible with the highly successful SPINE sample holder and with the miniSPINE and NewPin sample holders. Based on a six axis industrial robot, FlexED8 is equipped with a tool changer and includes a novel open sample-storage dewar with a built-in ice-filtering system. With seven versatile puck slots, it can hold up to 112 SPINE sample holders in uni-pucks, or 252 miniSPINE or NewPin sample holders, with 36 samples per puck. Additionally, a double gripper, compatible with the SPINE sample holders and uni-pucks, allows a reduction in the sample-exchange time from 40 s, the typical time with a standard single gripper, to less than 5 s. Computer vision-based sample-transfer monitoring, sophisticated error handling and automatic error-recovery procedures ensure high reliability. The FlexED8 sample changer has been successfully tested under real conditions on a beamline. PMID- 28994414 TI - Mismodeled purines: implicit alternates and hidden Hoogsteens. AB - Hoogsteen base pairs are seen in DNA crystal structures, but only rarely. This study tests whether Hoogsteens or other syn purines are either under-modeled or over-modeled, which are known problems for rare conformations. Candidate purines needing a syn/anti 180 degrees flip were identified by diagnostic patterns of difference electron-density peaks. Manual inspection narrowed 105 flip candidates to 20 convincing cases, all at <=2.7 A resolution. Rebuilding and refinement confirmed that 14 of these were authentic purine flips. Seven examples are modeled as Watson-Crick base pairs but should be Hoogsteens (commonest at duplex termini), and three had the opposite issue. Syn/anti flips were also needed for some single-stranded purines. Five of the 20 convincing cases arose from an unmodeled alternate duplex running in the opposite direction. These are in semi palindromic DNA sequences bound by a homodimeric protein and show flipped-purine like difference peaks at residues where the palindrome is imperfect. This study documents types of incorrect modeling which are worth avoiding. However, the primary conclusions are that such mistakes are infrequent, the bias towards fitting anti purines is very slight, and the occurrence rate of Hoogsteen base pairs in DNA crystal structures remains unchanged from earlier estimates at ~0.3%. PMID- 28994415 TI - SCI peer health coach influence on self-management with peers: a qualitative analysis. AB - STUDY DESIGN: A process evaluation of a clinical trial. OBJECTIVES: To describe the roles fulfilled by peer health coaches (PHCs) with spinal cord injury (SCI) during a randomized controlled trial research study called 'My Care My Call', a novel telephone-based, peer-led self-management intervention for adults with chronic SCI 1+ years after injury. SETTING: Connecticut and Greater Boston Area, MA, USA. METHODS: Directed content analysis was used to qualitatively examine information from 504 tele-coaching calls, conducted with 42 participants with SCI, by two trained SCI PHCs. Self-management was the focus of each 6-month PHC peer relationship. PHCs documented how and when they used the communication tools (CTs) and information delivery strategies (IDSs) they developed for the intervention. Interaction data were coded and analyzed to determine PHC roles in relation to CT and IDS utilization and application. RESULTS: PHCs performed three principal roles: Role Model, Supporter, and Advisor. Role Model interactions included CTs and IDSs that allowed PHCs to share personal experiences of managing and living with an SCI, including sharing their opinions and advice when appropriate. As Supporters, PHCs used CTs and IDSs to build credible relationships based on dependability and reassuring encouragement. PHCs fulfilled the unique role of Advisor using CTs and IDSs to teach and strategize with peers about SCI self-management. CONCLUSION: The SCI PHC performs a powerful, flexible role in promoting SCI self-management among peers. Analysis of PHC roles can inform the design of peer-led interventions and highlights the importance for the provision of peer mentor training. PMID- 28994416 TI - A high-quality genome assembly of quinoa provides insights into the molecular basis of salt bladder-based salinity tolerance and the exceptional nutritional value. AB - Chenopodium quinoa is a halophytic pseudocereal crop that is being cultivated in an ever-growing number of countries. Because quinoa is highly resistant to multiple abiotic stresses and its seed has a better nutritional value than any other major cereals, it is regarded as a future crop to ensure global food security. We generated a high-quality genome draft using an inbred line of the quinoa cultivar Real. The quinoa genome experienced one recent genome duplication about 4.3 million years ago, likely reflecting the genome fusion of two Chenopodium parents, in addition to the gamma paleohexaploidization reported for most eudicots. The genome is highly repetitive (64.5% repeat content) and contains 54 438 protein-coding genes and 192 microRNA genes, with more than 99.3% having orthologous genes from glycophylic species. Stress tolerance in quinoa is associated with the expansion of genes involved in ion and nutrient transport, ABA homeostasis and signaling, and enhanced basal-level ABA responses. Epidermal salt bladder cells exhibit similar characteristics as trichomes, with a significantly higher expression of genes related to energy import and ABA biosynthesis compared with the leaf lamina. The quinoa genome sequence provides insights into its exceptional nutritional value and the evolution of halophytes, enabling the identification of genes involved in salinity tolerance, and providing the basis for molecular breeding in quinoa. PMID- 28994417 TI - An essential role for PNLDC1 in piRNA 3' end trimming and male fertility in mice. PMID- 28994419 TI - Targeted therapy: ARIEL3 - broad benefit of PARP inhibitors in ovarian cancer. PMID- 28994420 TI - Lung Cancer: Dacomitinib delays disease progression. PMID- 28994418 TI - PTPN2: a tumor suppressor you want deleted? PMID- 28994421 TI - Breast cancer: LAG3 expression indicates favourable outcomes. PMID- 28994422 TI - Lung Cancer: SABR effective against oligometastatic disease. PMID- 28994424 TI - Thyroid cancer: Cabozantinib effective in selected patients. PMID- 28994425 TI - Targeting ligand-functionalized photothermal scaffolds for cancer cell capture and in situ ablation. AB - Scaffolds have been explored as a useful carrier to deliver efficient photothermal conversion agents for localized photothermal therapy applications because they can confine the agents in designated regions. However, cell capture by porous structures cannot discriminate between cancer cells and normal cells. In this study, folic acid (FA) as a typical targeting ligand for cancer cells was introduced into the porous photothermal scaffolds. Poly-l-lysine was mixed with gelatin to increase the amino side groups for FA incorporation. By changing the poly-l-lysine amount, the number of free amino groups in the scaffolds could be controlled. After the reaction with activated FA, composite scaffolds incorporated with different amounts of FA were prepared. Cell culture results showed that the FA-functionalized photothermal scaffolds could efficiently capture folate-positive cervical cancer cells compared with gelatin scaffolds. The capture efficiency increased with the increase in the amount of FA in the scaffolds. Furthermore, cancer cells in the FA-functionalized photothermal scaffolds can be efficiently killed during near-infrared laser irradiation. The results indicated that the FA-functionalized photothermal scaffolds had good cancer cell capture ability and excellent cancer cell ablation efficacy, which may provide useful information for the design of multifunctional scaffolds with cancer cell capture capacity and photothermal ablation ability. PMID- 28994430 TI - RGD-QD-MoS2 nanosheets for targeted fluorescent imaging and photothermal therapy of cancer. AB - The fast-developing field of nanotechnology provides unprecedented opportunities for the increasing demands of biomedicine, especially for cancer diagnostics and treatment. Here, novel multifunctional zero-dimensional-two-dimensional (0D-2D) RGD-QD-MoS2 nanosheets (NSs) with excellent fluorescence, photothermal conversion, and cancer-targeting properties were successfully prepared by functionalizing single-layer MoS2 NSs with fluorescent quantum dots (QDs) and arginine-glycine-aspartic (RGD) containing peptides. By using RGD-QD-MoS2 NSs as a multifunctional theranostic agent, targeted fluorescent imaging and photothermal therapy (PTT) of human cervical carcinoma (HeLa) cells were achieved. Moreover, HeLa tumors in mouse models can be fluorescently imaged and completely eradicated by photothermal irradiation using a low power NIR laser, due to the effective accumulation of RGD-QD-MoS2 NSs at the tumor sites through the RGD-integrin targeting and the enhanced penetration and retention (EPR) effect. Without exhibiting any appreciable toxicity to treated cells or animals, RGD-QD-MoS2 NSs have been demonstrated as promising multifunctional theranostic agents for cancer imaging and therapy. PMID- 28994431 TI - Nanodiamonds as pH-switchable oxidation and reduction catalysts with enzyme-like activities for immunoassay and antioxidant applications. AB - Nanodiamonds (NDs) have recently become a focus of interest from the viewpoints of both science and technology. Their intriguing properties make them suitable as biologically active substrates, in biosensor applications as well as diagnostic and therapeutic biomedical imaging probes. Here, we demonstrate that NDs, as oxidation and reduction catalysts, possess intrinsic enzyme mimetic properties of oxidase, peroxidase and catalase, and these behaviors can be switched by modulating the pH value. NDs not only catalyze the reduction of oxygen (O2) and hydrogen peroxide (H2O2) at acidic pH, but also catalyze the dismutation decomposition of H2O2 to produce O2 at alkaline pH. It was proposed that the molecular mechanism of their peroxidase-like activity is electron-transfer acceleration, the source of which is likely derived from oxygen containing functional groups on their surface. Based on the color reaction, a nanodiamond based enzyme linked immunosorbent assay (ELISA) was established for the detection of immunoglobulin G (IgG). Surprisingly, NDs display an excellent antioxidant activity due to the protective effect against H2O2-induced cellular oxidative damage. These findings make NDs a promising enzyme mimetic candidate and expand their applications in biocatalysis, bioassays and nano-biomedicine. PMID- 28994423 TI - Cholangiocarcinoma - evolving concepts and therapeutic strategies. AB - Cholangiocarcinoma is a disease entity comprising diverse epithelial tumours with features of cholangiocyte differentiation: cholangiocarcinomas are categorized according to anatomical location as intrahepatic (iCCA), perihilar (pCCA), or distal (dCCA). Each subtype has a distinct epidemiology, biology, prognosis, and strategy for clinical management. The incidence of cholangiocarcinoma, particularly iCCA, has increased globally over the past few decades. Surgical resection remains the mainstay of potentially curative treatment for all three disease subtypes, whereas liver transplantation after neoadjuvant chemoradiation is restricted to a subset of patients with early stage pCCA. For patients with advanced-stage or unresectable disease, locoregional and systemic chemotherapeutics are the primary treatment options. Improvements in external beam radiation therapy have facilitated the treatment of cholangiocarcinoma. Moreover, advances in comprehensive whole-exome and transcriptome sequencing have defined the genetic landscape of each cholangiocarcinoma subtype. Accordingly, promising molecular targets for precision medicine have been identified, and are being evaluated in clinical trials, including those exploring immunotherapy. Biomarker-driven trials, in which patients are stratified according to anatomical cholangiocarcinoma subtype and genetic aberrations, will be essential in the development of targeted therapies. Targeting the rich tumour stroma of cholangiocarcinoma in conjunction with targeted therapies might also be useful. Herein, we review the evolving developments in the epidemiology, pathogenesis, and management of cholangiocarcinoma. PMID- 28994432 TI - An intelligent NIR-responsive chelate copper-based anticancer nanoplatform for synergistic tumor targeted chemo-phototherapy. AB - The chelate copper-based anticancer drug bleomycin (BLM) is usually believed to bind metal ions especially Cu(ii) to generate the "activated BLM" for DNA cleavage. Herein, BLM and L-menthol (LM) co-loaded hollow mesoporous Cu2-xS nanoparticles (HMCu2-xS NPs) with surface folic acid (FA) modification were formulated to construct an intelligent NIR-responsive nanoplatform for synergistic tumor targeted chemo-phototherapy. With the tumor targeting ability of the folate receptor (FR)-positive, FA-HMCu2-xS/BLM/LM could pinpoint tumor cells efficiently. Under NIR irradiation, the versatile HMCu2-xS would be bound to exploit the merits of phototherapy (including PTT and PDT-like effects) for cancer treatment. Meanwhile, benefiting from the controllable "solid-liquid" (S L) phase transition feature of LM as a gatekeeper, FA-HMCu2-xS/BLM/LM offered a platform for simultaneous NIR-mediated temperature-responsive BLM and copper ion release, which further initiated the generation of the "activated BLM". As a matter of course, the remarkable synergistic combination of Cu-dependent chemo phototherapy in vitro and in vivo by such a smart all-in-one drug delivery nanoplatform developed here provided information for advancing nanotherapy in biomedical fields. PMID- 28994433 TI - Wafer-scale reliable switching memory based on 2-dimensional layered organic inorganic halide perovskite. AB - Recently, organic-inorganic halide perovskite (OHP) has been suggested as an alternative to oxides or chalcogenides in resistive switching memory devices due to low operating voltage, high ON/OFF ratio, and flexibility. The most studied OHP is 3-dimensional (3D) MAPbI3. However, MAPbI3 often exhibits less reliable switching behavior probably due to the uncontrollable random formation of conducting filaments. Here, we report the resistive switching property of 2 dimensional (2D) OHP and compare switching characteristics depending on structural dimensionality. The dimensionality is controlled by changing the composition of BA2MAn-1PbnI3n+1 (BA = butylammonium, MA = methylammonium), where 2D is formed from n = 1, and 3D is formed from n = infinity. Quasi 2D compositions with n = 2 and 3 are also compared. Transition from a high resistance state (HRS) to a low resistance state (LRS) occurs at 0.25 * 106 V m-1 for 2D BA2PbI4 film, which is lower than those for quasi 2D and 3D. Upon reducing the dimensionality from 3D to 2D, the ON/OFF ratio significantly increases from 102 to 107, which is mainly due to the decreased HRS current. A higher Schottky barrier and thermal activation energy are responsible for the low HRS current. We demonstrate for the first time reliable resistive switching from 4 inch wafer scale BA2PbI4 thin film working at both room temperature and a high temperature of 87 degrees C, which strongly suggests that 2D OHP is a promising candidate for resistive switching memory. PMID- 28994434 TI - Addressing carrier extraction from optically-optimized nanopillar arrays for thin film photovoltaics. AB - Decorating the top surface of silicon solar cells with nanopillar arrays of subwavelength periodicity is a promising path toward low-cost thin-film photovoltaics with enhanced solar radiation absorption due to the inherent light trapping capabilities of nanopillar arrays. Common practice and knowledge for the efficient carrier extraction from the excited nanopillars is the formation of ultra-shallow radial p-n junctions that provide both short carrier collection lengths, and also ensure that the volume of the photo inactive emitter is as small as possible. In the current manuscript, both finite-difference time-domain simulations and three-dimensional device simulations are used to examine carrier extraction from nanopillar arrays that are geometrically optimized in terms of array periodicity and nanopillar diameter to provide maximum absorption of the solar spectrum. The discussion is limited to nanopillars with heights of 2 MUm in line with what is currently available with leading top-down fabrication technologies for the formation of nanopillars with smooth sidewalls and radial uniformity. The examination considers both radial and axial homojunctions for various junction depths. It is shown that, contrary to common practice and knowledge, the ultra-shallow junctions are detrimental to the photovoltaic performance of such systems while the radial configuration with a junction depth of ~50 nm is the most efficient. Furthermore, the open circuit voltage is highest for axial junctions with a junction depth of 100 nm. Also, it is shown that the axial junction is preferable in the low dopant concentration regime and that overall, the axial junction is less sensitive to variations in junction depth. PMID- 28994435 TI - Hierarchical cobalt-nitride and -oxide co-doped porous carbon nanostructures for highly efficient and durable bifunctional oxygen reaction electrocatalysts. AB - Here we report the preparation of hollow microspheres with a thin shell composed of mixed cobalt nitride (Co-N) and cobalt oxide (Co-O) nanofragments encapsulated in thin layers of nitrogen-doped carbon (N-C) nanostructure (Co-N/Co-O@N-C) arrays with enhanced bifunctional oxygen electrochemical performance. The hybrid structures are synthesized via heat treatment of N-doped hollow carbon microspheres with cobalt nitrate, and both the specific ratio of these precursors and the selected annealing temperature are found to be the key factors for the formation of the unique hybrid structure. The as-obtained product (Co-N/Co-O@N-C) presents a large specific surface area (493 m2 g-1), high-level heteroatom doping (Co-N, Co-O, and N-C), and hierarchical porous nanoarchitecture containing macroporous frameworks and mesoporous walls. Electronic interaction between the thin N-C layers and the encapsulated Co-N and Co-O nanofragments efficiently optimizes oxygen adsorption properties on the Co-N/Co-O@N-C and thereby triggers bifunctional oxygen electrochemical activity at the surface. The Co-N/Co-O@N-C nanohybrid exhibited a high onset potential of 0.93 V, and a limiting current density of 5.6 mA cm-2 indicating 4-electron oxygen reduction reaction (ORR), afforded high catalytic activity for the oxygen evolution reaction (OER) and even exceeded the catalytic stability of the commercial precious electrocatalysts; furthermore, when integrated into the oxygen electrode of a regenerative fuel cell device, it exhibited high-performance oxygen electrodes for both the ORR and the OER. PMID- 28994436 TI - Engineering a periplasmic binding protein for amino acid sensors with improved binding properties. AB - Periplasmic binding proteins (PBPs) are members of a widely distributed protein superfamily found in bacteria and archaea, and are involved in the cellular uptake of solutes. In this report, a leucine-binding PBP was engineered to detect l-Leu based on a fluorescence resonance energy transfer (FRET) change upon ligand binding. A fluorescent unnatural amino acid, l-(7-hydroxycoumarin-4 yl)ethylglycine (CouA), was genetically incorporated into the protein as a FRET donor, and a yellow fluorescent protein (YFP) was fused with its N-terminus as a FRET acceptor. When CouA was incorporated into position 178, the sensor protein showed a 2.5-fold increase in the FRET ratio. Protein engineering significantly improved its substrate specificity, showing minimal changes in the FRET ratio with the other 19 natural amino acids and d-Leu. Further modification increased the sensitivity of the sensor protein (14-fold) towards l-Leu, and it recognized l-Met as well with moderate binding affinity. Selected mutant sensors were used to measure concentrations of l-Leu in a biological sample (fetal bovine serum) and to determine the optical purity of Leu and Met. This FRET-based sensor design strategy allowed us to easily manipulate the natural receptor to improve its binding affinity and specificity and to recognize other natural molecules, which are not recognized by the wild-type receptor. The design strategy can be applied to other natural receptors, enabling engineering receptors that sense biochemically interesting molecules. PMID- 28994437 TI - [(ZnSb6)2]4-: a new structure type for coupled norbornadiene-like subunits. AB - The norbornadiene-like bimetallic dimer [(ZnSb6)2]4- anion (1) was prepared by direct extraction from a ternary alloy with nominal composition "K6ZnSb5" in ethylenediamine/toluene/2,2,2-crypt solutions. The structure represents a new type for coupled norbornadiene subunits, however, distortions around the Zn2+ ions degrade the overall symmetry. The Zn2+ ions achieve a 16e- configuration and reside in near perfect ZnSb3 triangular coordination environments. DFT calculations reveal a 2.35 eV HOMO-LUMO gap and suggest covalent bonding between the Zn and Sb atoms. PMID- 28994438 TI - Biobased, self-healable, high strength rubber with tunicate cellulose nanocrystals. AB - Cellulose nanocrystals represent a promising and environmentally friendly reinforcing nanofiller for polymers, especially for rubbers and elastomers. Here, a simple approach via latex mixing is used to fabricate biobased, healable rubber with high strength based on epoxidized natural rubber (ENR). Tunicate cellulose nanocrystals (t-CNs) isolated from marine biomass with a high aspect ratio are used to improve both mechanical properties and self-healing behavior of the material. By introducing dynamic hydrogen bond supramolecular networks between oxygenous groups of ENR and hydroxyl groups on the t-CN surface, together with chain interdiffusion in permanently but slightly cross-linked rubber, self healing and mechanical properties are facilitated significantly in the resulting materials. Macroscopic tensile healing behavior and microscopic morphology analyses are carried out to evaluate the performance of the materials. Both t-CN content and healing time have significant influence on healing behavior. The results indicate that a synergistic effect between molecular interdiffusion and dynamic hydrogen bond supramolecular networks leads to the improved self-healing behavior. PMID- 28994439 TI - Enhanced surface acoustic wave cell sorting by 3D microfluidic-chip design. AB - We demonstrate an acoustic wave driven microfluidic cell sorter that combines advantages of multilayer device fabrication with planar surface acoustic wave excitation. We harness the strong vertical component of the refracted acoustic wave to enhance cell actuation by using an asymmetric flow field to increase cell deflection. Precise control of the 3-dimensional flow is realized by topographical structures implemented on the top of the microchannel. We experimentally quantify the effect of the structure dimensions and acoustic parameter. The design attains cell sorting rates and purities approaching those of state of the art fluorescence-activated cell sorters with all the advantages of microfluidic cell sorting. PMID- 28994440 TI - Influence of a pH-sensitive polymer on the structure of monoolein cubosomes. AB - Cubosomes consist in submicron size particles of lipid bicontinuous cubic phases stabilized by surfactant polymers. They provide an appealing road towards the practical use of lipid cubic phases for pharmaceutical and cosmetic applications, and efforts are currently being made to control the encapsulation and release properties of these colloidal objects. We overcome in this work the lack of sensitivity of monoolein cubosomes to pH conditions by using a pH sensitive polymer designed to strongly interact with the lipid structure at low pH. Our cryo-transmission electron microscope (cryo-TEM) and small-angle X-ray scattering (SAXS) results show that in the presence of the polymer the cubic phase structure is preserved at neutral pH, albeit with a larger cell size. At pH 5.5, in the presence of the polymer, the nanostructure of the cubosome particles is significantly altered, providing a pathway to design pH-responsive cubosomes for applications in drug delivery. PMID- 28994441 TI - A novel explanation for the enhanced colloidal stability of silver nanoparticles in the presence of an oppositely charged surfactant. AB - The structural behavior in aqueous mixtures of negatively charged silver nanoparticles (Ag NPs) together with the cationic surfactants cetyltrimethylammonium bromide (CTAB) and dodecyltrimethylammonium chloride (DTAC), respectively, has been investigated using SANS and SAXS. From our SANS data analysis we are able to conclude that the surfactants self-assemble into micellar clusters surrounding the Ag NPs. We are able to quantify our results by means of fitting experimental SANS data with a model based on cluster formation of micelles with very good agreement. Based on our experimental results, we propose a novel mechanism for the stabilization of negatively charged Ag NPs in a solution of positively charged surfactants in which cluster formation of micelles in the vicinity of the particles prevents the particles from aggregating. Complementary SAXS and DLS measurements further support this novel way of explaining stabilization of small hydrophilic nanoparticles in surfactant containing solutions. PMID- 28994442 TI - Dinuclear nitrido-bridged ruthenium complexes bearing diimine ligands. AB - Reactions of K3[Ru2NCl8(H2O)2] with 2,2'-bipyridine (bpy), 4,4'-dimethyl-2,2' bipyridine (dmbpy), and 4,4'-dimethoxy-2,2'-bipyridine (dmobpy) yielded the nitrido-bridged dinuclear complexes [Ru2N(L)2Cl5(DMF)] where L = bpy (1), dmbpy (2), and dmobpy (3). The crystal structures of these complexes reveal a linear Ru N-Ru moiety with each ruthenium center bearing a bidentate diimine ligand. The complexes were further characterized by NMR, IR, and UV-vis spectroscopic methods and cyclic voltammetry. Because the compounds bear some structural similarities with the mitochondrial calcium uptake inhibitor Ru360, the ability of these complexes to act in this capacity was evaluated. The results demonstrate that 1-3 all fail to block mitochondrial calcium uptake, revealing new facets of the structure-activity relationships for ruthenium-based mitochondrial calcium uptake inhibitors. PMID- 28994443 TI - Role of Raltegravir in patients co-infected with HIV and HCV in the era of direct antiviral agents. AB - Integrase strand transfer inhibitors (INSTIs) are the preferred third agent in first-line antiretroviral therapies. Raltegravir (RAL) was the first INSTI to be approved and used in naive and experienced patients. Due to its good tolerability and low side effects, RAL has been largely used also in hepatitis coinfected patients. Many years of experience in RAL use now allow literature evidence to be gathered on its safety in HIV/HCV-co-infected patients pre, during and post direct acting agents (DAA) treatment, at all possible stages. In both clinical trials and published case series, RAL has been well tolerated in patients harboring HCV co-infection and also in cirrhotic patients with mild hepatic impairment. Literature data show no major interactions or the need for dose adjustments with any of the DAA currently in use for HCV treatment, or with ribavirine. Hence, RAL can be safely administered during HCV treatment with DAA and may be used as a "temporary" regimen in patients who do not present major integrase-inhibitor mutations. Moreover, its characteristics are also favorable in case of orthotropic liver transplantation, both for the evidence of hepatic safety and for possible co-administration with immunosuppressant agents. PMID- 28994444 TI - Biomarkers of monitoring and functional reserve of physiological systems over time in HIV: expert opinions for effective secondary prevention. AB - HIV-positive individuals are more vulnerable to poor health than HIV-negative individuals. This vulnerability is characterized by a higher risk of several common, age-related health problems, even after adjustment for established risk factors. This expert opinion report aims at identifying the optimal biomarkers for monitoring the structural integrity and function of physiological systems at risk across aging in HIV-seropositive subjects. These biomarkers, readily available locally and relatively cost-effective for clinicians in primary and secondary care, should allow early detection of the first preclinical structural and functional changes in renal, brain, cardiovascular, and skeleton systems or apparatus in HIV subjects across aging. A particular interest of this report is the definition of the concept of biomarker of the "organ functional reserve". This definition emphasizes the fact that some biomarkers for monitoring the molecular, structural and functional integrity of a given organ reflect a level of impairment that is basically irremediable despite effective pharmacological or nonpharmacological intervention. PMID- 28994445 TI - Diagnostic performance of hepatitis E virus antigen assay in hepatitis E virus acute infection. AB - The aim of this study was to analyze the sensitivity of hepatitis E virus antigen (HEV-Ag) to determine acute E hepatitis. Ninety-four serum samples resulting anti HEV IgM by DIA.PRO assay were analyzed with Wantai assay to check for HEV-Ag. Thirty samples were anti-HEV IgM positive and HEV-RNA positive, 19 samples harbored genotype 3, whereas 11 samples were genotype 1. Overall, 16% of anti-HEV IgM samples resulted HEV-Ag positive and 33.3% of HEV-RNA positive were also HEV Ag positive. Among 64 HEV-RNA negative samples, 5 (7.8%) were HEV-Ag positive. The concordance of HEV-RNA and HEV-Ag was low (Cohen's Kappa=0.36). The Bland Altman plot revealed a low agreement between HEV-RNA viral load and HEV-Ag, confirmed by a not significant Spearman's correlation coefficient (rho=0.137, p>0.05). Moreover, the HEV-Ag showed 100% specificity. In genotype 3f samples with a viral load >800 cp/ml HEV-Ag was positive in 80% of samples, whereas all patients harboring genotype 3e were HEV-Ag-negative irrespective of HEV-RNA viral load. Among genotype 1, HEV-Ag positivity was observed only in 27.7% patients and in all samples the viremia was >2000 cp/ml. These data suggest that anti-HEV IgM positivity represents the main biological marker of hepatitis E acute infection in clinical real life settings in developed countries. PMID- 28994447 TI - Prevalence of Clostridium difficile and ribotype 027 infection in patients with nosocomial diarrhoea in Southern Italy. AB - Clostridium difficile is an emerging cause of healthcare-associated infections. The increasing frequency and severity is attributed to highly virulent ribotypes such as 027. The aim of this study was to retrospectively analyze the prevalence of CDI and ribotype 027 in 481 clinical samples collected from hospitalized patients and sent to the laboratory of molecular biology, UOC Microbiology and Virology, Azienda Ospedaliera-Universitaria, Policlinico of Bari, Italy. Toxins A+B and DNA C. difficile detections were performed using immunochromatographic test and a multiplex real-time PCR assay, respectively. Overall, 37/366 (10.11%) patients were positive at the immunochromatographic assay. This result was confirmed in 31 (8.47%) samples from 31 different patients by molecular assay. Logist regression confirmed age >50 years (adjusted odds ratio [aOR]: 4.29, 95%CI:1.44-18.50) and hospitalization in the Infectious Diseases (aOR: 3.77, 95%CI: 1.34-9.85) ward were risk factors for CDI. The associated 027 ribotype deletion D117tcd was detected in seven (22.58%) of 31 positive patients. Exploratory analysis of monthly prevalence of 027 ribotype suggested a slight increase after August 2015. Our results show that a monitoring program is needed to either better assess the diffusion of CDI and ribotype 027 or also to establish the risk factors associated with the transmission in our healthcare facilities. PMID- 28994446 TI - Colonization of residents and staff of an Italian long-term care facility and an adjacent acute care hospital geriatric unit by multidrug-resistant bacteria. AB - In 2016, we undertook a point prevalence screening study for Enterobacteriaceae with extended-spectrum beta-lactamases (ESBLs), high-level AmpC cephalosporinases and carbapenemases, and also methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin resistant enterococci (VRE) in a long-term care facility (LTCF) and the associated acute care hospital geriatric unit in Bolzano, Northern Italy. Urine samples and rectal, inguinal, oropharyngeal and nasal swabs were plated on selective agars. Demographic data were collected. ESBL and carbapenemase genes were sought by PCR. We found the following colonization percentages with multidrug-resistant (MDR) bacteria in 2016 in LTCF residents: all MDR organisms, 66.1%; ESBL producers, 53.0%; carbapenemase-producers, 1.7%; MRSA, 14.8%; VRE, 0.8%. Colonization by all MDR bacteria was 19.4% for LTCF staff and 26.0% for geriatric unit patients. PCR showed that 80.3% of Escherichia coli isolates from LTCF residents, all E. coli isolates from LTCF staff, 62.5% and 100% of Klebsiella pneumoniae from LTCF residents and geriatric unit patients, respectively, had a blaCTX-M-type gene. All carbapenemase-producing Enterobacteriaceae harboured a blaVIM-type gene. To conclude, the ongoing widespread diffusion of MDR bacteria in the LTCF suggests that efforts should be strengthened on MDR screening, implementation of infection control strategies and antibiotic stewardship programs targeting the unique aspects of LTCFs. PMID- 28994448 TI - Characterization of an IncL/M plasmid carrying blaOXA-48 in a Klebsiella pneumoniae strain from Italy. AB - Here we report the complete nucleotide sequence of a 49.257-bp IncL/M conjugative plasmid (pRAY) carrying the blaOXA-48 gene collected from a Klebsiella pneumoniae clinical strain isolated in Italy. The genetic environment of pRAY plasmid revealed that the blaOXA-48 gene was located within a Tn1999.2 transposon. The pRAY plasmid differed from blaOXA-48-harboring IncL/M plasmids by genetic context and size. Comparative analysis demonstrated that pRAY plasmid lacked a region of ~15 kb carrying genes encoding proteins involved in pilus assembly and plasmid conjugative apparatus. PMID- 28994449 TI - Postantifungal effect of micafungin against Candida albicans, Candida dubliniensis and Candida africana in the presence and absence of serum. AB - We compared the micafungin killing rate and postantifungal effect (PAFE) at 4, 16 and 32 mg/L in RPMI- 1640 and in 50% serum against the C. albicans complex. In RPMI-1640 PAFEs were 1.5 - >19.4, 9.7 - >20.1 and 15.9 - >18.5 hours for C. albicans, C. africana and C. dubliniensis, respectively. In 50% serum PAFEs decreased sharply to 0-1.7 hours for all three species; killing rates were always negative. Short growth inhibition without killing in 50% serum suggests that micafungin PAFE has a limited role in the eradication of the C. albicans complex from the bloodstream. PMID- 28994450 TI - The role of transient receptor potential channels in joint diseases. AB - Transient receptor potential channels (TRP channels) are cation selective transmembrane receptors with diverse structures, activation mechanisms and physiological functions. TRP channels act as cellular sensors for a plethora of stimuli, including temperature, membrane voltage, oxidative stress, mechanical stimuli, pH and endogenous, as well as, exogenous ligands, thereby illustrating their versatility. As such, TRP channels regulate various functions in both excitable and non-excitable cells, mainly by mediating Ca2+ homeostasis. Dysregulation of TRP channels is implicated in many pathologies, including cardiovascular diseases, muscular dystrophies and hyperalgesia. However, the importance of TRP channel expression, physiological function and regulation in chondrocytes and intervertebral disc (IVD) cells is largely unexplored. Osteoarthritis (OA) and degenerative disc disease (DDD) are chronic age-related disorders that significantly affect the quality of life by causing pain, activity limitation and disability. Furthermore, currently available therapies cannot effectively slow-down or stop progression of these diseases. Both OA and DDD are characterised by reduced tissue cellularity, enhanced inflammatory responses and molecular, structural and mechanical alterations of the extracellular matrix, hence affecting load distribution and reducing joint flexibility. However, knowledge on how chondrocytes and IVD cells sense their microenvironment and respond to its changes is still limited. In this review, we introduced six families of mammalian TRP channels, their mechanisms of activation, as well as, activation-driven cellular consequences. We summarised the current knowledge on TRP channel expression and activity in chondrocytes and IVD cells, as well as, the significance of TRP channels as therapeutic targets for the treatment of OA and DDD. PMID- 28994451 TI - Efficacy of the Danish epilepsy surgery programme. AB - OBJECTIVE: Despite optimal medical treatment, approximately one-third of patients with epilepsy continue to have seizures. Epilepsy surgery is widely accepted as a therapeutic option in the selected subset of patients with drug-resistant focal epilepsy. Here, we report the results of the Danish epilepsy surgery programme from 2009 to 2014. MATERIAL AND METHODS: A total of 169 consecutive patients, operated at Rigshospitalet, were included. Information was gathered from digital patient records. Before 1-year follow-up, two patients were lost to follow-up and three were referred to new surgery. RESULTS: The median years of drug resistance before operation were 11 years. At 1-year follow-up (n = 164), seizure outcomes were as follows: 65% Engel I (free from disabling seizures), 51% Engel IA (completely seizure free) and 9% Engel IV (no worthwhile improvement), and for patients operated in the medial temporal lobe (n = 114): 70% Engel I, 56% Engel IA, 5% Engel IV. The outcomes of the 53 patients needing intracranial EEG recording (ICR) were not significantly different from the patients only evaluated with surface EEG. None of the eight MRI-negative patients operated outside the medial temporal lobe after ICR were free of disabling seizures. 12% of MTLE patients developed de novo depression after epilepsy surgery despite good surgical outcome. Three patients required rehabilitation due to post-operative hemiplegia. CONCLUSION: The outcomes of the Danish epilepsy surgery programme align with international results found in recent meta-analyses. Serious complications to epilepsy surgery are seldom. In accordance with international recommendations, Danish drug-resistant patients should be referred to epilepsy surgery evaluation at an earlier stage of the disease. PMID- 28994453 TI - Effects of two different domestic boiling practices on the allergenicity of cow's milk proteins. AB - BACKGROUND: The sale of raw drinking milk through automatic dispensers is permitted in some EU member states, but consumers are usually advised to boil the milk before consumption. The present study has been conducted to evaluate the effects of two common domestic boiling techniques on the proteins of raw milk and, in particular, on their potential allergenicity. RESULTS: Native one dimensional electrophoresis, N-terminal amino acid sequencing and immunoblotting have been used to characterize the protein pattern and to evaluate the possible changes in the allergenic properties of the processed milk. The main result of this investigation is that heating induces the aggregation of beta-lactoglobulin in higher-molecular-weight products, while caseins seem to be more resistant to the treatments. beta-Lactoglobulin aggregates have been found to be non immunoreactive with the sera of subjects suffering from cow's milk protein allergy. CONCLUSION: Domestic boiling modifies the milk protein profile, causing a minor reduction in milk allergenicity. (c) 2017 Society of Chemical Industry. PMID- 28994452 TI - Comparison of the Guidelines of the Clinical Pharmacogenetics Implementation Consortium and the Dutch Pharmacogenetics Working Group. AB - Both the Clinical Pharmacogenetics Implementation Consortium (CPIC) and Dutch Pharmacogenetics Working Group provide therapeutic recommendations for well-known gene-drug pairs. Published recommendations show a high rate of concordance. However, as a result of different guideline development methods used by these two consortia, differences between the published guidelines exist. The aim of this paper is to compare both initiatives and explore these differences, with the objective to achieve harmonization. PMID- 28994454 TI - Healthcare professionals' work engagement in Finnish university hospitals. AB - BACKGROUND: Concerns about the sufficiency and dedication of the healthcare workforce have arisen as the baby boomer generation is retiring and the generation Y might have different working environment demands. AIMS AND OBJECTIVE: To describe the association between work engagement of healthcare professionals' and its background factors at five Finnish university hospitals. METHODS: Survey data were collected from nurses, physicians and administrative staff (n = 561) at all five university hospitals in Finland. Data were collected using an electronic questionnaire that comprised the Utrecht Work Engagement Scale (9 items) and 13 questions regarding the respondents' backgrounds. Descriptive and correlational analyses were used to examine the data. RESULTS: Most respondents were female (85%) and nursing staff (72%). Baby boomers (49%) were the largest generational cohort. The work engagement composite mean for the total sample was 5.0, indicating high work engagement. Significant differences in work engagement existed only among sex and age groups. The highest work engagement scores were among administrative staff. CONCLUSIONS: Work engagement among healthcare professionals in Finnish university hospitals is high. High work engagement might be explained by suitable job resources and challenges, as well as opportunities provided by a frontline care environment. Attention should especially be paid to meeting the needs of young people entering the workforce to strengthen their dedication and absorption. PMID- 28994455 TI - Fluoridation cessation: More science from Alberta. PMID- 28994456 TI - 'The other right': control strategies and the role of language use in laparoscopic training. AB - CONTEXT: Laparoscopic techniques present a particular challenge to the academic surgeon in maintaining control and patient safety. The authors explored the use of verbal and physical control strategies including deixis, language used to locate subject in spatio-temporal, social and discoursal contexts, in this setting. METHODS: Forty cases of laparoscopic cholecystectomy at an academic centre were video and audio-recorded. Surgeon and trainee discourses and physical gestures during the crucial anatomical steps of the operation were qualitatively analysed using a hybrid inductive and deductive technique with explicit attention to the use of deixis. RESULTS: Laparoscopic surgeon educators use verbal and physical strategies and engage in bidirectional communication to maintain indirect control of an operation where direct control is not possible. Among verbal strategies, deictic language predominates. DISCUSSION: As in open surgery, laparoscopic surgical educators attempt to exert control over surgical procedures when the instruments are in the hands of a trainee. One dominant strategy is the use of deictic language, which may be ambiguous. In addition to the physical manoeuvres and bidirectional communication used to disambiguate, instructors must attend to potential uncertainties and explicitly clarify frames of reference in order to enhance educational experiences and maximise patient safety. PMID- 28994457 TI - Back from basics: integration of science and practice in medical education. AB - CONTEXT: In 1988, the Edinburgh Declaration challenged medical teachers, curriculum designers and leaders to make an organised effort to change medical education for the better. Among a series of recommendations was a call to integrate training in science and clinical practice across a breadth of clinical contexts. The aim was to create physicians who could serve the needs of all people and provide care in a multitude of contexts. In the years since, in the numerous efforts towards integration, new models of curricula have been proposed and implemented with varying levels of success. SCOPE OF REVIEW: In this paper, we examine the evolution of curricular integration since the Edinburgh Declaration, and discuss theoretical advances and practical solutions. In doing so, we draw on recent consensus reports on the state of medical education, emblematic initiatives reported in the literature, and developments in education theory pertinent to the role of integrated curricula. CONCLUSIONS: Interest in integration persists despite 30 years of efforts to respond to the Edinburgh Declaration. We argue, however, that a critical shift has taken place with respect to the conception of integration, whereby empirical models support a view of integration as pertaining to both cognitive activity and curricular structure. In addition, we describe a broader definition of 'basic science' relevant to clinical practice that encompasses social and behavioural sciences, as well as knowledge derived from biomedical science. PMID- 28994458 TI - A blind deconvolution method incorporated with anatomical-based filtering for partial volume correction: Validations with 123 I-mIBG cardiac SPECT/CT. AB - PURPOSE: Segmentation of contrast-enhanced CT and measurement of SPECT point spread function (PSF) are usually required for conventional partial volume correction (PVC). This study was to develop a segmentation-free method with blind deconvolution (BD) and anatomical-based filtering for SPECT PVC. METHODS: The proposed method was implemented using an iterative BD algorithm to estimate the restored image and the PSF simultaneously. An anatomical-based filtering was implemented at each iteration to reduce Gibbs artifact and suppress noise amplification in the deconvolution process. The proposed method was validated with 123 I-metaiodobenzylguanidine (123 I-mIBG) SPECT/CT imaging of NCAT phantoms with and without myocardial perfusion defect and a physical cardiac phantom. Fifteen heart-to-mediastinum ratios (HMRs) were configured in the NCAT and physical phantoms. Correlations between SPECT-quantified and true HMRs were calculated from images without PVC as well as from BD restored images. The proposed method was also performed on a human 123 I-mIBG study. RESULTS: Relative bias and standard deviation images of NCAT phantoms showed that the proposed method reduced both bias and noise. Mean relative bias in the simulated normal myocardium was markedly improved (-16.8% +/- 0.4% versus -0.8% +/- 0.6% for low noise level; -16.7% +/- 0.7% versus -2.3% +/- 0.9% for high noise level). Mean relative bias in the simulated myocardial defect was also noticeably improved ( 12.7% +/- 1.2% versus 1.2% +/- 1.6% for low noise level; -13.5% +/- 2.4% versus 0.9% +/- 2.8% for high noise level). The signal to noise ratio (SNR) of the defect was improved from 2.95 +/- 0.09 to 4.07 +/- 0.16 for low noise level (38% increase of mean), and from 2.56 +/- 0.15 to 3.62 +/- 0.22 for high noise level (41% increase of mean). For both NCAT and physical phantoms, HMRs calculated from images without PVC were underestimated (correlations between SPECT-quantified and true HMRs: y = 0.81x + 0.1 for NCAT phantom; y = 0.82x + 0.14 for physical phantom). HMRs from BD restored images were markedly improved (correlations between SPECT-quantified and true HMRs: y = x + 0.05 for NCAT phantom; y = 0.97x 0.12 for physical phantom). After applying the proposed PVC method, the estimation error between the SPECT-quantified and true HMRs was significantly reduced from -0.75 +/- 0.57 to 0.04 +/- 0.17 for NCAT phantom (P = 8e-05), and from -0.68 +/- 0.67 to -0.26 +/- 0.42 for physical phantom (P = 0.005). The human study demonstrated that the HMR increased by 8% with PVC. CONCLUSIONS: The proposed segmentation-free PVC method has the potential of improving SPECT quantification accuracy and reducing noise without the need for premeasuring the image PSF. PMID- 28994460 TI - Ethical considerations when conducting joint interviews with close relatives or family: an integrative review. AB - BACKGROUND: Researchers are obligated to do no harm to participants of research. Conflicts in relationships can cause negative well-being; therefore, insight is needed into the particular ethical considerations that arise when conducting joint interviews with close relatives or family members simultaneously in the healthcare setting. AIM: To collect and share knowledge related to ethical considerations conducting joint interviews. DESIGN AND METHODS: A literature review inspired by the integrative review method was performed. Data were retrieved through a structured search in PubMed, CINAHL and the Philosopher's Index and Academic Search Premier for articles published in English from 1980 to 2016 and included 18 articles, of a possible 2153. Article content was assessed line-by-line, and ethical considerations were extracted and organized in three subgroups regarding: Planning joint interviews; Conduction joint interviews and Reporting on joint interviews Findings: Participants should be offered the best terms for a constructive, on-going relationship after the joint interview has ended. This obligates the researcher to ensure a safe environment during the joint interview and create a delicate balance between the needs of the participants, using nonconfrontational techniques that foster equal and neutral but dedicated attention to all parties, before, during and after the joint interviews. CONCLUSION: Specific ethical considerations should be taken into account before, during and after joint interviewing. Further research is needed before a final conclusion can be drawn. PMID- 28994459 TI - Neural network dose models for knowledge-based planning in pancreatic SBRT. AB - PURPOSE: Stereotactic body radiation therapy (SBRT) for pancreatic cancer requires a skillful approach to deliver ablative doses to the tumor while limiting dose to the highly sensitive duodenum, stomach, and small bowel. Here, we develop knowledge-based artificial neural network dose models (ANN-DMs) to predict dose distributions that would be approved by experienced physicians. METHODS: Arc-based SBRT treatment plans for 43 pancreatic cancer patients were planned, delivering 30-33 Gy in five fractions. Treatments were overseen by one of two physicians with individual treatment approaches, with variations in prescribed dose, target volume delineation, and primary organs at risk. Using dose distributions calculated by a commercial treatment planning system (TPS), physician-approved treatment plans were used to train ANN-DMs that could predict physician-approved dose distributions based on a set of geometric parameters (vary from voxel to voxel) and plan parameters (constant across all voxels for a given patient). Patient datasets were randomly allocated, with two-thirds used for training, and one-third used for validation. Differences between TPS and ANN DM dose distributions were used to evaluate model performance. ANN-DM design, including neural network structure and parameter choices, was evaluated to optimize dose model performance. RESULTS: Remarkable improvements in ANN-DM accuracy (i.e., from > 30% to < 5% mean absolute dose error, relative to the prescribed dose) were achieved by training separate dose models for the treatment style of each physician. Increased neural network complexity (i.e., more layers, more neurons per layer) did not improve dose model accuracy. Mean dose errors were less than 5% at all distances from the PTV, and mean absolute dose errors were on the order of 5%, but no more than 10%. Dose-volume histogram errors (in cm3 ) demonstrated good model performance above 25 Gy, but much larger errors were seen at lower doses. CONCLUSIONS: ANN-DM dose distributions showed excellent overall agreement with TPS dose distributions, and accuracy was substantially improved when each physician's treatment approach was taken into account by training their own dedicated models. In this manner, one could feasibly train ANN DMs that could predict the dose distribution desired by a given physician for a given treatment site. PMID- 28994461 TI - Implantable cardioverter-defibrillator in the elderly: Predictors of appropriate interventions and mortality at 12-month follow-up. AB - BACKGROUND: The effectiveness of implantable cardioverter-defibrillator (ICD) in the elderly is uncertain, given their competing risk of nonarrhythmic death. Guidelines state that an ICD should be implanted if the expectation of survival is at least 1 year. However, survival is not easy to predict in elderly patients with severe cardiac disease. AIM: To assess 12-month survival after ICD implantation in patients aged >=75 years, to identify predictors of 12-month mortality, and to evaluate the incidence of ICD therapy during follow-up. METHODS: We retrospectively analyzed all clinical, instrumental, and survival data of patients >=75 years old who received an ICD in our center from 2000 to 2013. RESULTS: We included 127 patients (mean age 78 years). ICD was implanted for primary prevention in 61%. The 12-month survival rate was 87.4%. At both univariate and multivariate analyses, left ventricular ejection fraction (EF) <= 25%, and moderate to severe impaired renal function (IRF) independently predicted 12-month mortality that was as high as 45.5% in patients with both risk factors. During a median follow-up of 38 months, 30 patients (23.6%) received >=1 appropriate ICD interventions, but only 3.1% of shocks occurred during the first year, and none in the subgroup of patients with EF <= 25% and IRF. CONCLUSION: Twelve-month survival in elderly patients after ICD implantation is good and the indication for ICD should not be based on age alone. However, the subgroup with EF <= 25% and IRF showed a high 12-month nonarrhythmic mortality and did not benefit from ICD implantation. PMID- 28994462 TI - Limitations of fluoridation effectiveness studies: Lessons from Alberta, Canada. AB - A paper published in this journal, "Measuring the short-term impact of fluoridation cessation on dental caries in Grade 2 children using tooth surface indices," by McLaren et al had shortcomings in study design and interpretation of results, and did not include important pertinent data. Its pre-post cross sectional design relied on comparison of decay rates in two cities: Calgary, which ceased fluoridation, and Edmonton, which maintained fluoridation. Dental health surveys conducted in both cities about 6.5 years prior to fluoridation cessation in Calgary provided the baseline. They were compared to decay rates determined about 2.5 years after cessation in a second set of surveys in both cities. A key shortcoming was the failure to use data from a Calgary dental health survey conducted about 1.5 years prior to cessation. When this third data set is considered, the rate of increase of decay in Calgary is found to be the same before and after cessation of fluoridation, thus contradicting the main conclusion of the paper that cessation was associated with an adverse effect on oral health. Furthermore, the study design is vulnerable to confounding by caries risk factors other than fluoridation: The two cities differed substantially in baseline decay rates, other health indicators, and demographic characteristics associated with caries risk, and these risk factors were not shown to shift in parallel in Edmonton and Calgary through time. An additional weakness was low participation rates in the dental surveys and lack of analysis to check whether this may have resulted in selection biases. Owing to these weaknesses, the study has limited ability to assess whether fluoridation cessation caused an increase in decay. The study's findings, when considered with the additional information from the third Calgary survey, more strongly support the conclusion that cessation of fluoridation had no effect on decay rate. Consideration of the limitations of this study can stimulate improvement in the quality of future fluoridation effectiveness studies. PMID- 28994463 TI - Prognosis, risk stratification, and management of asymptomatic individuals with Brugada syndrome: A systematic review. AB - Brugada syndrome (BrS) is a primary electrical disease associated with increased risk of sudden cardiac death due to polymorphic ventricular arrhythmias. The prognosis, risk stratification, and management of asymptomatic individuals remain the most controversial issues in BrS. Furthermore, the decision to manage asymptomatic patients with an implantable cardioverter-defibrillator should be made after weighing the potential individual risk of future arrhythmic events against the risk of complications associated with the implant and follow-up of patients living with such devices, and the accompanying impairment of the quality of life. Several clinical, electrocardiographic, and electrophysiological markers have been proposed for risk stratification of subjects with BrS phenotype, but the majority have not yet been tested in a prospective manner in asymptomatic individuals. Recent data suggest that current risk factors are insufficient and cannot accurately predict sudden cardiac death events in this setting. This systematic review aims to discuss contemporary data regarding prognosis, risk stratification, and management of asymptomatic individuals with diagnosis of Brugada electrocardiogram pattern and to delineate the therapeutic approach in such cases. PMID- 28994464 TI - Dosimetric consequences of gold nanoparticle clustering during photon irradiation. AB - PURPOSE: The radiation dose enhancement caused by introducing gold nanoparticles (GNP) into cells can increase the dose locally absorbed. A disconnect between experimentally determined survival and dose enhancements predicted by Monte Carlo simulations on macroscopic scales, suggests small-scale energy deposition patterns play an important role in GNP dose enhancement. Clustering of the GNPs could potentially alter small-scale energy deposition patterns. Here we use Monte Carlo simulations to quantify energy deposition patterns in the presence of clustered GNPs and address the question of whether clustering of the nanoparticles affects the energy deposition patterns and ultimately cellular response. METHODS: Using the PENELOPE Monte Carlo code, we examine the absorption of energy in the environment of a single irradiated GNP following its interaction with a set of primary monoenergetic photon beams. We introduce successive GNPs to form a cluster about the particle in which the primary photon interactions occur and report on the energy deposited locally (within a 500 nm radius) and nonlocally (beyond 500 nm) in the surrounding water-equivalent medium as a function of the number of additional GNPs and the packing geometry they assume. RESULTS: When additional GNPs cluster in tightly packed formations about a GNP in which an incident photon interacts, both the energy deposited locally and released nonlocally are reduced relative to the case where other GNPs are not present. The degree of the reduction depends on incident photon energy, the number of GNPs added to the cluster, and the packing geometry. With 90 additional GNPs in a hexagonal close packing (HCP) cluster about a directly irradiated test particle, the local energy deposition was reduced to 29% (of the value in the absence of neighbors) in the most extreme monoenergetic case. Energy released into the nonlocal volume was most affected by the cluster for low-incident photon energies (< 40 keV), where reductions to 26% of the value in the absence of a cluster were shown. The packing geometry mitigated these results. When the irradiated GNP was on the periphery of the HCP cluster, or when the cluster was confined to a plane, the observed effects were weaker and when an equal number of GNPs were uniformly distributed in the local volume, the changes were trivial (less than 2%). CONCLUSIONS: The findings provide grounds for reconciling the observations of cell survival with Monte Carlo predictions of GNP dose enhancement. This work is significant because it demonstrates that GNP clustering needs to be understood and accounted to optimize local dose enhancement. PMID- 28994465 TI - Impact of PET/CT system, reconstruction protocol, data analysis method, and repositioning on PET/CT precision: An experimental evaluation using an oncology and brain phantom. AB - PURPOSE: In longitudinal oncological and brain PET/CT studies, it is important to understand the repeatability of quantitative PET metrics in order to assess change in tracer uptake. The present studies were performed in order to assess precision as function of PET/CT system, reconstruction protocol, analysis method, scan duration (or image noise), and repositioning in the field of view. METHODS: Multiple (repeated) scans have been performed using a NEMA image quality (IQ) phantom and a 3D Hoffman brain phantom filled with 18 F solutions on two systems. Studies were performed with and without randomly (< 2 cm) repositioning the phantom and all scans (12 replicates for IQ phantom and 10 replicates for Hoffman brain phantom) were performed at equal count statistics. For the NEMA IQ phantom, we studied the recovery coefficients (RC) of the maximum (SUVmax ), peak (SUVpeak ), and mean (SUVmean ) uptake in each sphere as a function of experimental conditions (noise level, reconstruction settings, and phantom repositioning). For the 3D Hoffman phantom, the mean activity concentration was determined within several volumes of interest and activity recovery and its precision was studied as function of experimental conditions. RESULTS: The impact of phantom repositioning on RC precision was mainly seen on the Philips Ingenuity PET/CT, especially in the case of smaller spheres (< 17 mm diameter, P < 0.05). This effect was much smaller for the Siemens Biograph system. When exploring SUVmax , SUVpeak , or SUVmean of the spheres in the NEMA IQ phantom, it was observed that precision depended on phantom repositioning, reconstruction algorithm, and scan duration, with SUVmax being most and SUVpeak least sensitive to phantom repositioning. For the brain phantom, regional averaged SUVs were only minimally affected by phantom repositioning (< 2 cm). CONCLUSION: The precision of quantitative PET metrics depends on the combination of reconstruction protocol, data analysis methods and scan duration (scan statistics). Moreover, precision was also affected by phantom repositioning but its impact depended on the data analysis method in combination with the reconstructed voxel size (tissue fraction effect). This study suggests that for oncological PET studies the use of SUVpeak may be preferred over SUVmax because SUVpeak is less sensitive to patient repositioning/tumor sampling. PMID- 28994466 TI - Chilled to the bone: embodied countertransference and unspoken traumatic memories. AB - Starting from a deeply challenging experience of early embodied countertransference in a first encounter with a new patient, the author explores the issues it raised. Such moments highlight projective identification as well as what Stone (2006) has described as 'embodied resonance in the countertransference'. In these powerful experiences linear time and subject boundaries are altered, and this leads to central questions about analytic work. As well as discussing the uncanny experience at the very beginning of an analytic encounter and its challenges for the analytic field, the author considers 'the time horizon of analytic process' (Hogenson ), the relationship between 'moments of complexity and analytic boundaries' (Cambray ) and the role of mirror neurons in intersubjective experience. PMID- 28994468 TI - The historicity and potential of Jungian analysis: another view of 'SWOT'. PMID- 28994469 TI - Transgenderism and transformation: an attempt at a Jungian understanding. AB - While transgenderism as a cultural phenomenon seems to be based on a collective taste for the sensational, its emergence represents a collective shift towards a new or more differentiated way of experiencing and expressing sex and gender, a movement of world soul. This paper attempts to explore that emergence from a Jungian perspective. The paper utilizes clinical examples which illustrate how dissociated aspects of the personality are seeking assimilation and expression in order to move the personality towards greater wholeness. In that sense, it attempts to understand the teleology of transgenderism on an individual and collective level. The paper is intended as a starting-off point for discussion and explores gender as fantasy, anima/animus dynamics, the psyche/soma relationship, the role of hormones/biochemistry in our experience of ourselves and what transgender people carry and suffer for our culture. PMID- 28994471 TI - God of the hinge: treating LGBTQIA patients. AB - This paper looks at systems of gender within the context of analysis. It explores the unique challenges of individuation faced by transsexual, transgender, gender queer, gender non-conforming, cross-dressing and intersex patients. To receive patients generously we need to learn how a binary culture produces profound and chronic trauma. These patients wrestle with being who they are whilst simultaneously receiving negative projections and feeling invisible. While often presenting with the struggles of gender conforming individuals, understanding the specifically gendered aspect of their identity is imperative. An analyst's unconscious bias may lead to iatrogenic shaming. The author argues that rigorous, humble inquiry into the analyst's transphobia can be transformative for patient, analyst, and the work itself. Analysis may, then, provide gender-variant patients with their first remembered and numinous experience of authentic connection to self. Conjuring the image of a hinge, securely placed in the neutral region of a third space, creates a transpositive analytic temenos. Invoking the spirit of the Trickster in the construction of this matrix supports the full inclusion of gender-variant patients. Nuanced attunement scaffolds mirroring and the possibility of play. Being mindful that gender is sturdy and delicate as well as mercurial and defined enriches the analyst's listening. PMID- 28994472 TI - The future of Jungian analysis: strengths, weaknesses, opportunities, threats ('SWOT'). AB - Using a methodology derived from management and organizational studies, the author reviews the future of Jungian analysis. The methodology is termed SWOT - strengths, weaknesses, opportunities, threats. A selected list in each of these categories is presented. The author is transparent in allowing for the fact that the paper not only derives from a public lecture on the topic, but also retains the immediacy and the contrarian and opinionated style of such a lecture. PMID- 28994473 TI - Preliminary thoughts on the neurobiology of innate unconscious structures and the psychodynamics of language acquisition. AB - This paper builds upon Britton's recent writing on 'models in the mind', in which he gives an account of preverbal metaphoric structures based on object relations (Britton 2015). These correspond with Jung's theory of innate unconscious structures. These innate models are considered alongside current linguistic theory following Chomsky and post-Chomskyan views about language acquisition. Neuroscience evidence linking language and abstract thinking with structures involved in tool use are presented. The implications of these findings, and our understanding of the relational context within which language, metaphor and abstract thought are acquired, will be discussed along with the failures of symbolization and verbal communication common amongst those with severe narcissistic disorders. PMID- 28994474 TI - The wrong side of history. AB - Psychoanalysis (including analytical psychology), once a pioneering and forward looking movement of the early 20th century has now become a conservative backward looking 'tradition'. After considering some of the internal problems associated with this historical change such as idealization and tribalism, some ways forward are suggested - a focus on clinical excellence as practical craft, openness to the unknown and engagement with others beyond the confines of private practice. PMID- 28994477 TI - Editorial. PMID- 28994476 TI - The words we work with that work on us: clinical paradigm and cumulative relational trauma. AB - This paper addresses a gap between analytic clinical theory and practice which emerges when examining the words we work with via textual and narrative research of case histories. Both subject matter and methodology fit with the remit of conceptual research in psychoanalysis, currently ranging from inductive to nomothetical approaches. Research of clinical language reveals an implicit account of human nature and the world which undergirds clinical practice. Based in the critical philosophy of the previous century, this is termed clinical paradigm. Such implicit views are induced rather than explicitly taught during analytic training, and need to be spelled out in order to become available to discourse and difference of opinion. Textual research shows these implicit pre clinical attitudes to be inherently pessimistic and thus too similar to the views of self and others found in cumulative relational trauma. Moreover, clinical accounts tend to normalize subtly antagonistic forms of relating, recently recognised as micro-trauma. Importantly, this contravenes the agapic orientation of our theories and ethics. Paradigmatic reflection as a form of professional individuation addresses this gap. This includes a more optimistic outlook which can be traced through the philosophical implications of quantum theory. PMID- 28994478 TI - Treatment of developmental stress disorder: mind, body and brain - analysis and pharmacology coupled. AB - The schism between psychiatry, psychology and analysis, while long present, has widened even more in the past half-century with the advances in psychopharmacology. With the advances in electronic brain imaging, particularly in developmental and post-traumatic stress disorders, there has emerged both an understanding of brain changes resulting from severe, chronic stress and an ability to target brain chemistry in ways that can relieve clinical symptomatology. The use of alpha-1 adrenergic brain receptor antagonists decreases many of the manifestations of PTSD. Additionally, this paper discusses the ways in which dreaming, thinking and the analytic process are facilitated with this concomitant treatment and hypervigilence and hyper-arousal states are signficiantly decreased. PMID- 28994479 TI - Bureaucracy and creativity: do they make companionable bedfellows? AB - This essay will look at the benefits and weaknesses of the increasingly bureaucratic nature of training structures and processes in the training of Jungian psychotherapists and analysts. The author will draw on her experiences during two different periods of time as Director of Training at the Society of Analytical Psychology in London with observations on and discussion about some of the changes that have evolved. By way of contrast, she will offer some comparisons with developments in the training of Jungian analysts in countries with little or no legacy of an analytic culture. Here, there is a need to professionalize training in Jungian analysis but the attendant growth of bureaucracy can easily come to echo the politics of non-democratic regimes. PMID- 28994480 TI - Andrei Tarkovsky: stalker of the unconscious. PMID- 28994481 TI - Unconscious choice: the dissociation of creative animus among writers and psychotherapists. AB - The paper argues that writers and psychotherapists are drawn to their work through the desire to remedy an unconscious sense of lack brought about by early relational trauma. Often, because of its origins in psychic pain, the connection between these individuals' beginnings and their profession remains largely dissociated. The theme is developed with reference to the idea of the wounded healer taken up by Jung. It is proposed that the original wound is also the crack that lets the light in: a dissociated tough spirit that can be channelled into discriminating countertransference and strong writing. This paper is implicitly arguing against an objective or neutral analytic stance, and for the therapeutic and creative value of acquaintance with negative affect. PMID- 28994483 TI - 'Clemency on the way to the gallows': death, dreams and dissociation. AB - The survivor of a decade of childhood sexual trauma and violence, perpetrated by a monstrous father, produced a series of dreams in the final year of a ten-year analysis. They illuminated the 'death drive' beneath a lifelong preoccupation with dying and fantasies of submission to death, perpetuated by the promise of hoped-for freedom from pain and release from a life of suffering. The initial dream involved the collapse of a team of white horses drawing him in a pillory cart to his own hanging for a crime he did not commit. It signified the collapse of a fragile psychological system based on his role as the 'sacrificial lamb,' protecting a (not so) innocent mother. The raw truth was now unconcealed: primal, violent, and terrifying dreams and affects emerged where he was now the murderous aggressor. His dreams would become primary agents for an instinctive, life-giving authenticity to emerge, offering him clemency from the shattering repetitions of persecution and dissociation. PMID- 28994484 TI - Brief remarks on Toshio Kawai's response to my SAP lecture. PMID- 28994486 TI - Mitigation of near-band balanced steady-state free precession through-plane flow artifacts using partial dephasing. AB - PURPOSE: To mitigate artifacts from through-plane flow at the locations of steady state stopbands in balanced steady-state free precession (SSFP) using partial dephasing. METHODS: A 60 degrees range in the phase accrual during a TR was created over the voxel by slightly unbalancing the slice-select dephaser. The spectral profiles of SSFP with partial dephasing for various constant flow rates and during pulsatile flow were simulated to determine if partial dephasing decreases through-plane flow artifacts originating near SSFP dark bands while maintaining on-resonant signal. Simulations were then validated in a flow phantom. Lastly, phase-cycled SSFP cardiac cine images were acquired with and without partial dephasing in six subjects. RESULTS: Partial dephasing decreased the strength and non-linearity of the dependence of the signal at the stopbands on the through-plane flow rate. It thus mitigated hyper-enhancement from out-of slice signal contributions and transient-related artifacts caused by variable flow both in the phantom and in vivo. In six volunteers, partial dephasing noticeably decreased artifacts in all of the phase-cycled cardiac cine datasets. CONCLUSION: Partial dephasing can mitigate the flow artifacts seen at the stopbands in balanced SSFP while maintaining the sequence's desired signal. By mitigating hyper-enhancement and transient-related artifacts originating from the stopbands, partial dephasing facilitates robust multiple-acquisition phase-cycled SSFP in the heart. Magn Reson Med 79:2944-2953, 2018. (c) 2017 International Society for Magnetic Resonance in Medicine. PMID- 28994485 TI - Modified risk stratification grouping using standard clinical and biopsy information for patients undergoing radical prostatectomy: Results from SEARCH. AB - INTRODUCTION: Prostate cancer is a heterogeneous disease, and risk stratification systems have been proposed to guide treatment decisions. However, significant heterogeneity remains for those with unfavorable-risk disease. METHODS: This study included 3335 patients undergoing radical prostatectomy without adjuvant radiotherapy in the SEARCH database. High-risk patients were dichotomized into standard and very high-risk (VHR) groups based on primary Gleason pattern, percentage of positive biopsy cores (PPBC), number of NCCN high-risk factors, and stage T3b-T4 disease. Similarly, intermediate-risk prostate cancer was separated into favorable and unfavorable groups based on primary Gleason pattern, PPBC, and number of NCCN intermediate-risk factors. RESULTS: Median follow-up was 78 months. Patients with VHR prostate cancer had significantly worse PSA relapse free survival (PSA-RFS, P < 0.001), distant metastasis (DM, P = 0.004), and prostate cancer-specific mortality (PCSM, P = 0.015) in comparison to standard high-risk (SHR) patients in multivariable analyses. By contrast, there was no significant difference in PSA-RFS, DM, or PCSM between SHR and unfavorable intermediate-risk (UIR) patients. Therefore, we propose a novel risk stratification system: Group 1 (low-risk), Group 2 (favorable intermediate-risk), Group 3 (UIR and SHR), and Group 4 (VHR). The c-index of this new grouping was 0.683 for PSA-RFS and 0.800 for metastases, compared to NCCN-risk groups which yield 0.666 for PSA-RFS and 0.764 for metastases. CONCLUSIONS: Patients classified as VHR have markedly increased rates of PSA relapse, DM, and PCSM in comparison to SHR patients, whereas UIR and SHR patients have similar prognosis. Novel therapeutic strategies are needed for patients with VHR, likely involving multimodality therapy. PMID- 28994487 TI - Scan-rescan of axcaliber, macromolecular tissue volume, and g-ratio in the spinal cord. AB - PURPOSE: Recent MRI techniques have been introduced that can extract microstructural information in the white matter, such as the density or macromolecular content. Translating quantitative MRI to the clinic raises many challenges in terms of acquisition strategy, modeling of the MRI signal, artifact corrections, and metric extraction (template registration and partial volume effects). In this work, we investigated the scan-rescan repeatability of several quantitative MRI techniques in the human spinal cord. METHODS: AxCaliber metrics, macromolecular tissue volume, and the fiber g-ratio were estimated in the spinal cord of eight healthy subjects, scanned and rescanned the same day in two different sessions. RESULTS: Scan-rescan repeatability deviation was 3% for all metrics, in average in the white matter of all subjects. Intraclass correlation coefficient was up to 0.9. A three-way analysis of variance showed significant effects of white matter pathway, laterality, and subject. CONCLUSION: The present study suggests that quantitative MRI gives stable measurements of white matter microstructure in the spinal cord of healthy subjects. Our findings remain to be evaluated in diseased populations. Magn Reson Med 79:2759-2765, 2018. (c) 2017 International Society for Magnetic Resonance in Medicine. PMID- 28994488 TI - Families' experiences of raising concerns in health care services: An interpretative phenomenological analysis. AB - BACKGROUND: This exploratory study aimed to increase understanding of the experiences of families of people with intellectual disabilities when noticing and raising concerns in services. A qualitative design was employed. METHODS: Seven participants (all female) were recruited through local and national voluntary agencies; five were mothers of people with intellectual disabilities, one was the aunt and one the sister. Participants took part in semi-structured interviews centred on their experiences of noticing and raising concerns, these were recorded and transcribed. The data were analyzed using interpretative phenomenological analysis (IPA; Smith, 1996). RESULTS: The data were grouped into three superordinate themes: the nature and importance of concerns, relationships between familes and staff and the process of raising concerns. A key and surprising finding was the importance of "the little things." CONCLUSIONS: This research highlights important implications for services such as the need to simplify the process of raising concerns, attend to the relationship with families and ensure advocacy services are identified for those without family. PMID- 28994489 TI - Short-term resource allocation during extensive athletic competition. AB - OBJECTIVES: Following predictions from life history theory, we sought to identify acute trade-offs between reproductive effort (as measured by psychological arousal) and somatic maintenance (via functional measures of innate immunity) during conditions of severe energetic imbalance. METHODS: Sixty-six male ultramarathon runners (ages 20 to 37 years) were sampled before and after a lengthy race. Saliva and sera were collected for testosterone and immunological analyses (hemolytic complement activity and bacterial killing ability). Lean body mass was assessed by bioelectrical impedance, and libido was measured using a slideshow of arousing and neutral images. RESULTS: Following predictions, there was a significant decrease in salivary testosterone levels (109.59 pg/mL versus 97.61 pg/mL, P < .001) and arousal scores in response to provocative images (5.40 versus 4.89, P = .001) between prerace and postrace time points. Additionally, participant bacterial killing ability (P = .035) and hemolytic complement activity (P = .021) increased between prerace and postrace. CONCLUSIONS: Decreased libido and testosterone with concomitant heightened innate immune responses suggest a shift in energetic priorities away from reproduction and toward maintenance/defense during a period of energetic stress. PMID- 28994490 TI - Computed tomographic findings in 205 dogs with clinical signs compatible with middle ear disease: a retrospective study. AB - BACKGROUND: Computed tomography (CT) is considered to be the reference method to evaluate middle ear structures. OBJECTIVES: To evaluate the presence and severity of CT changes in the middle ear and establish if any specific clinical presentations are associated with otitis media. ANIMALS: Medical records of animals referred for CT with history and clinical signs consistent with middle ear disease. METHODS: Retrospective evaluation of CT examinations of tympanic bullae performed over a six year period. Medical records were reviewed for signalment, clinical signs and cytological evaluation of the external ear canal. Dogs were divided into three clinical groups: chronic otitis externa (Group 1), peripheral vestibular disorder (Group 2) and other clinical presentations (Group 3). RESULTS: Group 1 - Of 214 ears, 87 (40.7%) had CT abnormalities: 38 of 87 (17.7%) had material-filled bullae, 42 of 87 (19.6%) had thickened bullae walls and seven of 87 (3.2%) had lysis of the bulla. Abnormalities were significantly more frequent in dogs with suppurative otitis than in erythemato-ceruminous otitis (57% and 23%, respectively; P = 0.003). Proliferative otitis, particularly in French bulldogs, was associated with severe otitis media. Group 2 - Of the 106 ears, 91 (85.8%) had normal tympanic bullae. Group 3 - Of the 26 ears from deaf dogs, 17 had filled bullae; all nine affected dogs were Cavalier King Charles spaniels. All dogs with Claude Bernard Horner syndrome or head tilt had normal tympanic bullae. CLINICAL SIGNIFICANCE: CT is useful for canine chronic otitis externa, particularly in suppurative or proliferative otitis, even in the absence of associated neurological signs. PMID- 28994491 TI - Slow-Photon-Effect-Induced Photoelectrical-Conversion Efficiency Enhancement for Carbon-Quantum-Dot-Sensitized Inorganic CsPbBr3 Inverse Opal Perovskite Solar Cells. AB - All-inorganic cesium lead halide perovskite is suggested as a promising candidate for perovskite solar cells due to its prominent thermal stability and comparable light absorption ability. Designing textured perovskite films rather than using planar-architectural perovskites can indeed optimize the optical and photoelectrical conversion performance of perovskite photovoltaics. Herein, for the first time, this study demonstrates a rational strategy for fabricating carbon quantum dot (CQD-) sensitized all-inorganic CsPbBr3 perovskite inverse opal (IO) films via a template-assisted, spin-coating method. CsPbBr3 IO introduces slow-photon effect from tunable photonic band gaps, displaying novel optical response property visible to naked eyes, while CQD inlaid among the IO frameworks not only broadens the light absorption range but also improves the charge transfer process. Applied in the perovskite solar cells, compared with planar CsPbBr3 , slow-photon effect of CsPbBr3 IO greatly enhances the light utilization, while CQD effectively facilitates the electron-hole extraction and injection process, prolongs the carrier lifetime, jointly contributing to a double-boosted power conversion efficiency (PCE) of 8.29% and an increased incident photon-to-electron conversion efficiency of up to 76.9%. The present strategy on CsPbBr3 IO to enhance perovskite PCE can be extended to rationally design other novel optoelectronic devices. PMID- 28994492 TI - Quality of clinical brain tumor MR spectra judged by humans and machine learning tools. AB - PURPOSE: To investigate and compare human judgment and machine learning tools for quality assessment of clinical MR spectra of brain tumors. METHODS: A very large set of 2574 single voxel spectra with short and long echo time from the eTUMOUR and INTERPRET databases were used for this analysis. Original human quality ratings from these studies as well as new human guidelines were used to train different machine learning algorithms for automatic quality control (AQC) based on various feature extraction methods and classification tools. The performance was compared with variance in human judgment. RESULTS: AQC built using the RUSBoost classifier that combats imbalanced training data performed best. When furnished with a large range of spectral and derived features where the most crucial ones had been selected by the TreeBagger algorithm it showed better specificity (98%) in judging spectra from an independent test-set than previously published methods. Optimal performance was reached with a virtual three-class ranking system. CONCLUSION: Our results suggest that feature space should be relatively large for the case of MR tumor spectra and that three-class labels may be beneficial for AQC. The best AQC algorithm showed a performance in rejecting spectra that was comparable to that of a panel of human expert spectroscopists. Magn Reson Med 79:2500-2510, 2018. (c) 2017 International Society for Magnetic Resonance in Medicine. PMID- 28994493 TI - Biofilm removal potential of neutral electrolysed water on pathogen and spoilage bacteria in dairy model systems. AB - AIMS: This study aimed to investigate the efficacy of neutral electrolysed water (NEW) on biofilm and planktonic forms of Listeria monocytogenes, Escherichia coli and Pseudomonas aeruginosa in Luria-Bertani (LB) broth, 0.5 and 3% w/w fat pasteurized and ultra high temperature (UHT) milk. METHODS AND RESULTS: Biofilm was established on stainless steels in a simulated industrial model biofilm reactor. NEW had a bactericidal effect on planktonic forms of all bacteria at 25 MUg ml-1 concentration. Biofilm production index (BPI) was affected by the type of media and micro-organisms and incubation temperatures. In general, biofilms were more intense at 22 degrees C in milk containing 3% fat than 0.5% fat and LB. The highest BPI (1.12) was reported for the biofilm of E. coli at 22 degrees C in 3% fat pasteurized milk. No significant change in biofilm formation for any bacteria at UHT and pasteurized milk was obtained. NEW at 75 MUg ml-1 concentration had more significant biofilm removal activity on all the tested bacteria. The biofilm removal property of NEW in high-fat milk was lower than that in low-fat milk and LB broth. CONCLUSIONS: NEW can be used at 75 MUg ml-1 concentration as a sanitizing and biofilm removal compound in dairy plant facilities. SIGNIFICANCE AND IMPACT OF THE STUDY: This study highlighted the effect of different growth media, including culture media and different types of milk, and the biofilm removal activity of NEW on foodborne pathogens and spoilage bacteria which could be considered in plant sanitation schedule. PMID- 28994494 TI - Development of a Thai version of the paediatric bleeding assessment tool (Thai paediatric-BAT) suitable for use in children with inherited mucocutaneous bleeding disorders. PMID- 28994495 TI - Ankyloglossia as a risk factor for maxillary hypoplasia and soft palate elongation: A functional - morphological study. AB - OBJECTIVES: To characterize associations between restricted tongue mobility and maxillofacial development. SETTING AND SAMPLE POPULATION: Cross-sectional cohort study of 302 consecutive subjects from an orthodontic practice. MATERIAL AND METHODS: Tongue mobility (measured with tongue range of motion ratio [TRMR] and Kotlow free tongue measurement) was correlated with measurements of the maxillofacial skeleton obtained from dental casts and cephalometric radiographs. RESULTS: Tongue range of motion ratio and Kotlow measures of restricted tongue mobility were associated with (i) ratio of maxillary intercanine width to canine arch length, (ii) ratio of maxillary intermolar width to canine arch length and (iii) soft palate length. Restricted tongue mobility was not associated with hyoid bone position or Angle's skeletal classification. CONCLUSIONS: Restricted tongue mobility was associated with narrowing of the maxillary arch and elongation of the soft palate in this study. These findings suggest that variations in tongue mobility may affect maxillofacial development. PMID- 28994496 TI - Effects of Bithiophene Imide Fusion on the Device Performance of Organic Thin Film Transistors and All-Polymer Solar Cells. AB - Two new bithiophene imide (BTI)-based n-type polymers were synthesized. f-BTI2-FT based on a fused BTI dimer showed a smaller band gap, a lower LUMO, and higher crystallinity than s-BTI2-FT containing a BTI dimer connected through a single bond. s-BTI2-FT exhibited a remarkable electron mobility of 0.82 cm2 V-1 s-1 , and f-BTI2-FT showed a further improved mobility of 1.13 cm2 V-1 s-1 in transistors. When blended with the polymer donor PTB7-Th, f-BTI2-FT-based all polymer solar cells (all-PSCs) attained a PCE of 6.85 %, the highest value for an all-PSC not based on naphthalene (or perylene) diimide polymer acceptors. However, s-BTI2-FT all-PSCs showed nearly no photovoltaic effect. The results demonstrate that f-BTI2-FT is one of most promising n-type polymers and that ring fusion offers an effective approach for designing polymers with improved electrical properties. PMID- 28994499 TI - Re: Moderately elevated blood pressure during pregnancy and odds of hypertension later in life: The POUCHmoms longitudinal study Potential mechanism for pregnant and nonpregnant hypertension: Authors' reply. PMID- 28994498 TI - A Three-Dimensionally pi-Conjugated Diradical Molecular Cage. AB - pi-Conjugated molecular cages are very challenging targets in structural organic chemistry, supramolecular chemistry, and materials science. The synthesis and physical characterizations are reported of the first three-dimensionally pi conjugated diradical molecular cage PTM-C, in which two polychlorotriphenylmethyl (PTM) radicals are linked by three bis(3,6-carbazolyl) bridges. This cage compound was synthesized mainly by intermolecular Yamamoto coupling followed by deprotonation and oxidation. It is stable and its structure was confirmed by X ray crystallographic analysis. The two carbon-centered PTM radicals are weakly coupled through electronic interactions with the carbazole spacers, as revealed by optical, electronic, and magnetic measurements as well as theoretical calculations. PMID- 28994497 TI - Effects of Vernonia cinerea Compounds on Drug-metabolizing Cytochrome P450s in Human Liver Microsomes. AB - Vernonia cinerea has been widely used in traditional medicines for various diseases and shown to aid in smoking abstinence and has anticancer properties. V. cinerea bioactive compounds, including flavonoids and hirsutinolide-type sesquiterpene lactones, have shown an inhibition effect on the nicotine metabolizing cytochrome P450 2A6 (CYP2A6) enzyme and hirsutinolides reported suppressing cancer growth. In this study, V. cinerea ethanol extract and its bioactive compounds, including four flavonoids and four hirsutinolides, were investigated for an inhibitory effect on human liver microsomal CYPs 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4 using cocktail inhibition assays combined with LC-MS/MS analysis. Among tested flavonoids, chrysoeriol was more potent in inhibition on CYP2A6 and CYP1A2 than other liver CYPs, with better binding efficiency toward CYP2A6 than CYP1A2 (Ki values in competitive mode of 1.93 +/- 0.05 versus 3.39 +/- 0.21 MUM, respectively). Hirsutinolides were prominent inhibitors of CYP2A6 and CYP2D6, with IC50 values of 12-23 and 15-41 MUM, respectively. These hirsutinolides demonstrated time-dependent inhibition, an indication of mechanism-based inactivation, toward CYP2A6. Quantitative prediction of microsomal metabolism of these flavonoids and hirsutinolides, including half-lives and hepatic clearance rate, was examined. These findings may have implications for further in vivo studies of V. cinerea. Copyright (c) 2017 John Wiley & Sons, Ltd. PMID- 28994500 TI - The Cysteinome of Protein Kinases as a Target in Drug Development. AB - Drugs that function through covalent bond formation represent a considerable fraction of our repository of effective medicines but safety concerns and the complexity of developing covalent inhibitors has rendered covalent targeting a less attractive strategy for rational drug design. The recent approval of four covalent kinase inhibitors and the development of highly potent covalent kinase probes with exceptional selectivity has raised significant interest in industry and academic research and validated the concept of covalent kinase targeting for clinical applications. The abundance of cysteines at diverse positions in and around the kinase active site suggests that a large fraction of kinases can be targeted by covalent inhibitors. Herein, we review recent developments of this rapidly growing area in kinase drug development and highlight the unique opportunities and challenges of this strategy. PMID- 28994501 TI - Decoupled Thermo- and pH-Responsive Hydrogel Microspheres Cross-Linked by Rotaxane Networks. AB - Rotaxane cross-linked (RC) microgels that exhibit a decoupled thermo- and pH responsive volume transition were developed. The pH-induced changes of the aggregation/disaggregation states of cyclodextrin in the RC networks were used to control the swelling capacity of the entire microgels. Different from conventional thermo- and pH-responsive microgels, which are usually obtained from copolymerizations involving charged monomers, the RC microgels respond to temperature as intended, even in the presence of charged functional molecules such as dyes in the microgel dispersion. The results of this study should lead to new applications, including drug delivery systems that require a retention of their smart functions even in environments that may contain foreign ions, for example, in in vivo experiments. PMID- 28994503 TI - Authors' reply re: Trends in operative vaginal delivery, 2005-2013: a population based study. PMID- 28994502 TI - Pro-protein subtilisin kexin-9 (PCSK9) inhibition in practice: lipid clinic experience in 2 contrasting UK centres. AB - BACKGROUND: Prescribing criteria have been suggested for proprotein convertase subtilisin kexin-9 (PCSK-9) inhibitors but few studies exist of their real-world effectiveness. METHODS: This study audited PCSK-9 inhibitor therapy in 105 consecutive patients from two hospital centres-a university hospital (UH; n = 70) and a district general hospital (DGH; n = 35). Baseline characteristics including cardiovascular disease risk factors, NICE qualification criteria, efficacy and side effects were assessed. RESULTS: Baseline LDL-C levels were similar in both centres. NICE criteria were met for 2.05 items in the whole study (UH patients 1.7 and DGH patients 2.7). District general hospital patients were more likely to have familial hypercholesterolaemia (89 vs 69%; P = .02); intolerance to statins (94 vs 52%; P < .001) and polyvascular disease (42% vs 17%; P = .005). Prescriptions (evolocumab 73%; alirocumab 23%) were collected by 76% of patients (UH 64% vs DGH 100%). Therapy was discontinued by time of review in 15% of patients (UH 7% vs DGH 25%; P = .02). In adherent patients PCSK-9 inhibitor treatment reduced TC by 28% (2.24 +/- 2.39 mmol/L; P < .001) and LDL-C by 49% (2.10 +/- 1.33 mmol/L; P < .001). A LDL-C < 2.5 mmol/L was achieved in 30% of patients and <2.0 mmol/L in 20%. PCSK-9 therapy was effective and safe in patients with increased lipoprotein (a), diagnosed muscle diseases (including myopathies and muscular dystrophy) or poststatin rhabdomyolysis, nephrotic syndrome or HIV disease. Mixed results were obtained in patients with significant mixed hyperlipidaemia. CONCLUSIONS: This study suggests that PCSK-9 inhibitors are effective but that prescriptions should not be changed to long-term delivery until patients have been reviewed and shown to be adherent. PMID- 28994504 TI - Selective Activation of C-H Bonds in a Cascade Process Combining Photochemistry and Biocatalysis. AB - Selective oxyfunctionalizations of inert C-H bonds can be achieved under mild conditions by using peroxygenases. This approach, however, suffers from the poor robustness of these enzymes in the presence of hydrogen peroxide as the stoichiometric oxidant. Herein, we demonstrate that inorganic photocatalysts such as gold-titanium dioxide efficiently provide H2 O2 through the methanol-driven reductive activation of ambient oxygen in amounts that ensure that the enzyme remains highly active and stable. Using this approach, the stereoselective hydroxylation of ethylbenzene to (R)-1-phenylethanol was achieved with high enantioselectivity (>98 % ee) and excellent turnover numbers for the biocatalyst (>71 000). PMID- 28994505 TI - Lithiation Behavior of Silicon Nanowire Anodes for Lithium-Ion Batteries: Impact of Functionalization and Porosity. AB - Metal-assisted chemical etching (MACE) provides a versatile way to synthesize silicon nanowires (SiNW) of different morphologies. MACE was used to synthesize oxide-free porous and nonporous SiNW for use as anodes for lithium-ion batteries. To improve their processing behavior, the SiNW were functionalized using acrylic acid. Differential capacity plots were used as a way to identify the degradation processes during cycling through tracking the formation of Li15 Si4 and changes in polarization. The cycling performance between porous and nonporous SiNW differed regarding Coulombic efficiency and cycling stability. The differences were attributed to the porous hull and its ability to reduce the volume expansion, although not through its porous nature but the reduced uptake of Li ions. PMID- 28994506 TI - Inflammatory cells in liquid-based cytology smears classified as bacterial vaginosis. AB - BACKGROUND: Bacterial vaginosis (BV) remains an enigmatic question. The term "osis" instead of "itis" is used because commonly, there are no inflammatory process associated with BV. However, leukocytes are often observed in it. METHODS: In a transversal study, we evaluated 1178 cases with diagnosis of BV by liquid-based cytology (more than 20% of clue cells), attended in general gynecologic private clinic. Depending of the presence of more than five leukocytes on average per field in immersion objective (1000*), the cases were divided in two groups: few or no leukocytes (< 5 leukocytes per field) (BV) and with leukocytes (>= 5 leukocytes per field) (BV-L). The Fisher exact and Student t tests was applied to a confidence interval of 95%. The project was approved by the Ethic Committee of Federal University of Ceara, Brazil. RESULTS: The age between the groups was the only different socio-demographic variable. The assessment of vaginal discharge aspect had no characteristic aspect. Colposcopy findings suggesting colpitis and ectopy were more frequent in the group of BV-L, 7.1% and 6.9%, respectively. The study of the microbiology demonstrated in the BV L group, more frequently co-occurrence of Candida sp (15.1%) than in BV group (1.5%) (P < .0001). The cellular atypia was present more frequently in the BV-L (9.6%) than in BV (5.7%) (P = .0116). CONCLUSION: The presence of leukocytes in BV (or BV-L) may suggest a mixed infection, ectopy influencing the vaginal milieu and even epithelial atypia. PMID- 28994507 TI - Re: Trends in operative vaginal delivery, 2005-2013: a population-based study. PMID- 28994508 TI - Loss of BRCA1-associated protein 1 (BAP1) expression is useful in diagnostic cytopathology of malignant mesothelioma in effusions. AB - BACKGROUND: The important diagnostic challenge facing the cytopathologist is whether a mesothelial proliferation on effusions represents a malignant mesothelioma (MM) or a benign mesothelial hyperplasia (MH). Here, we evaluated the diagnostic utility of BAP1 immunohistochemistry (IHC) in distinguishing between reactive and neoplastic mesothelial cells. METHODS: In pleural and peritoneal effusions from 147 patients with diagnosed MM or with a differential diagnosis of MM and MH, the expression of BAP1 was examined by IHC on paraffin embedded cell blocks (n = 121) and biopsies (n = 44). Included were also synchronous and methacronous cytology/biopsy pair samples. BAP1 IHC was evaluated for nuclear staining as positive or negative on target mesothelial cells, with appropriate internal control. RESULTS: In MM cases, loss of BAP1 nuclear staining was observed in 76.5% of the cell blocks and 47.5% of the biopsies. All BAP1 negative cases with a differential diagnosis of benign and malignant mesothelial proliferations were MM at follow-up. All MH cases, the 29% of epithelial MM and the 90% of nonepithelial MM, retained BAP1 expression. Synchronous and methacronous biopsy/cytology pairs showed matching BAP1 results. CONCLUSION: In effusions with mesotheliomatous cells or atypical mesothelial cells of uncertain significance, negative BAP1 IHC strongly supports a diagnosis of MM. With prudence in interpreting immunostaining, BAP1 may be included in IHC panels for MM cytodiagnosis, given its high specificity and sensitivity. PMID- 28994509 TI - Cytology of breast pleomorphic adenoma associated with extensive apocrine metaplasia. PMID- 28994510 TI - Isolated lingual cysticercosis: A rare case diagnosed on cytology. AB - Cysticercosis is caused by larval stage of Taenia solium called cysticercus cellulosae. Cysticercosis most commonly infects skeletal muscles, subcutaneous tissues, brain and ocular tissue. On extensive search of literature, only around 64 cases of lingual cysticercosis have been reported till date. We report a case of cysticercosis of tongue in a 35-year-old male who presented with a painless, slowly growing swelling over the lateral border of tongue. Fine needle aspiration cytology revealed wavy integument of cysticercus cellulosae alongwith inflammatory cells. The findings were confirmed on histopathology. No other cystic swelling was encountered in the body on retrospective examination and investigations. This case is being presented on account of its rarity as well as the utility of FNAC as a primary diagnostic technique in evaluation of parasitic lesions. PMID- 28994511 TI - Relationships of family conflict, cohesion, and chaos in the home environment on maternal and child food-related behaviours. AB - This study examined how food-related behaviours differed in mothers and their preschool children by levels of family functioning (cohesion and conflict) and household disorganization (chaos). A nationally representative sample of mothers of preschoolers completed an online survey assessing food-related behaviours of themselves and their children. Maternal and child diet, eating behaviours, and health status; household availability of fruits/vegetables, salty/fatty snacks, and sugar-sweetened beverages; family mealtime atmosphere; and family conflict, cohesion, and household chaos were assessed with valid, reliable scales. Cluster analyses assigned families into low, middle, and high conflict, cohesion, and chaos groups. Participants (n = 550) were 72% White, and 82% had some post secondary education. Regression analysis examining the association of cluster grouping levels on diet-related behaviour measures revealed that positive home environments (i.e., low family conflict, high family cohesion, and low household chaos) were associated with healthier food-related behaviours (e.g., increased fruits/vegetables intake), whereas negative home environments (i.e., high family conflict, low family cohesion, and high household chaos) were associated with unhealthy food-related behaviours (e.g., greater % total calories from fat) even after controlling for sociodemographic and related behavioural factors. Findings suggest family functioning and household chaos are associated with food-related behaviours. This frequently overlooked component of family interaction may affect intervention outcomes and objectives of educational and interventional initiatives. PMID- 28994512 TI - Creating effective and engaging presentations. PMID- 28994513 TI - Authors reply re: Clinical follow up of women after hypertensive disease in pregnancy. PMID- 28994514 TI - Six domains to develop critical medical humanities. PMID- 28994515 TI - Role of pelvic ultrasound simulation. AB - BACKGROUND: Pelvic ultrasound is a critical diagnostic imaging tool in obstetrics and gynaecology. Training opportunities in transvaginal ultrasound have not kept pace with the demand among learners because of the increased complexity of modern ultrasound technology and duty-hour restrictions. Ultrasound simulation training has the potential to overcome this gap. Training opportunities in transvaginal ultrasound have not kept pace with the demand OBJECTIVE: Our study aimed to determine the usefulness, applicability and attitudes toward pelvic ultrasound simulation training among residents, sonographers and practising doctors. METHODS: Pelvic ultrasound simulation activity using high-fidelity virtual reality ultrasound simulators lasted 4 hours and consisted of three modules: abnormal uterine bleeding, adnexal masses and bleeding in pregnancy. All learners completed a pre- and post-encounter quiz, and an anonymous post-simulation survey on the relevance of ultrasound simulation to clinical learning, and its usefulness to improve scanning performance and interpretation skills. RESULTS: Thirty-one participants attended the workshop, and 28 (90.3%) of them responded to the survey. Five respondents agreed and 23 strongly agreed that pelvic ultrasound simulation applies to their clinical ultrasound practice, and seven of them agreed and 21 strongly agreed that their performance of ultrasound and interpretation skills will be improved following their simulation training. The average post-activity knowledge score for all three topics significantly increased (paired Student's t-test, p < 0.0001). CONCLUSIONS: All 28 respondents believe that ultrasound simulation is a useful complement to learning with real patients, with the potential to improve their pelvic ultrasound performance, interpretation skills and clinical reasoning. PMID- 28994516 TI - The Implication of Combat Stress and PTSD Trajectories in Metabolic Syndrome and Elevated C-Reactive Protein Levels: A Longitudinal Study. AB - OBJECTIVE: This study sheds light on the importance of long-term follow-up of trauma survivors, posttraumatic stress disorder (PTSD) trajectories, and early detection of health risk factors in trauma survivors. The present study prospectively assessed the following over 23 years: (1) the association of psychological and physiologic stress during captivity with elevated C-reactive protein (CRP) levels and metabolic syndrome (MetS), which includes hypertension; elevated levels of insulin, triglycerides, and fasting glucose; decreased levels of high-density lipoprotein cholesterol; and obesity and (2) the implication of PTSD trajectories in elevated CRP levels and MetS. METHODS: Measurements were taken in 1991, 2003, 2008, and 2015. Participants were 116 Israeli combat veterans of the 1973 Yom Kippur War (of these, 101 were former prisoners of war [ex-POWs] and 15 were comparable controls). The medical assessments relevant for this study were body mass index, fasting blood glucose levels, and diabetes, blood pressure or a diagnosis of hypertension, high-density lipoprotein cholesterol and triglyceride levels, and medication intake. In addition, the PTSD Inventory was used to assess PTSD symptoms and trajectories over time according to DSM-IV-TR PTSD criteria. RESULTS: Captivity-in particular, the captivity stressors of weight loss, physical suffering, psychological suffering, and humiliation-was implicated in both elevated CRP levels and MetS, significantly so with elevated CRP levels (P = .01, R2 = 0.33). Captivity-induced PTSD, in particular chronic and delayed PTSD trajectories, was associated with elevated CRP levels and MetS, significantly so for MetS (P = .05). CONCLUSIONS: Monitoring inflammation using markers like CRP level in trauma survivors can be beneficial, particularly if PTSD is chronic or delayed. Clinicians treating trauma survivors should raise awareness of the importance of such measures in light of long-term health vulnerabilities. PMID- 28994517 TI - The Impact of Obesity on Cognitive Functioning in Euthymic Bipolar Patients: A Cross-Sectional and Longitudinal Study. AB - OBJECTIVE: To determine the influence of body mass index (BMI) on cognition in euthymic bipolar patients and healthy matched controls in a post hoc study of 2 cross-sectional and longitudinal exploratory studies. METHOD: A total sample of 121 individuals was examined, which included 52 euthymic bipolar disorder I or II patients (DSM-IV-TR criteria) and 69 healthy controls matched by age and gender, categorized in 2 subgroups in terms of body mass index (BMI-factor): normal weight (BMI: 18.5-24.9 kg/m2) versus overweight-obesity (overweight, BMI: 25.0 29.9 kg/m2; and obese, BMI >= 30 kg/m2). Demographic, clinical, cognitive, and psychosocial functioning data were collected from 2003 until 2011. Cognitive domains studied were executive function, attention, processing speed, verbal memory, and visual memory. Fifty-four subjects (28 bipolar and 26 healthy controls) were reevaluated after 6 years of follow-up. RESULTS: Obesity and bipolar disorder showed a significant effect on cognition in cross-sectional and long-term MANOVA analyses (F7,111 = 2.54, P = .018 and F19,23 = 2.25, P = .033, respectively). In the cross-sectional linear regression model, global cognitive functioning was predicted by the interaction of BMI-factor by group (beta = 0.44, SE = 0.14, P = .002), current age (beta = -0.44, P < .0001), and premorbid IQ (beta = 0.28, P = .0002), which explained 56% of variance (F5,115 = 29.6, P < .0001). Change in cognitive functioning over time was predicted by the interaction of BMI-factor by group (beta = -0.8, SE = 0.33, P = .022) and cognition at baseline (beta = -0.46, SE = 0.15, P = .004), which explained 27.65% of variance (F6,40 = 2.548, P = .0349). Generalized estimating equations analysis showed that interaction of group by BMI (Wald chi21 = 5.37, P = .02), age (Wald chi21 = 22.08, P < .0001), and premorbid IQ (Wald chi21 = 25.65, P < .0001) were the significant predictors. CONCLUSIONS: Obesity was significantly associated with cognitive impairment in euthymic bipolar patients, and it also appeared to affect cognition in the long term. PMID- 28994518 TI - [Quality evaluation of decoction of single medicinal herb--a case of Lonicerae Japinicae Flos]. AB - Decoction of single medicinal herb is a reference for the standardization of different dosage form of Chinese medicine and it provides a new direction for solving the problems existing in the quality of Chinese medicinal granules such no uniform dosage forms and no clear quality standard. There are few reports on the idea, method and preparation of single herb standard decoction. Our country is in urgent need of that information in order to improve the consistency and stability of traditional Chinese medicine products. Here, Lonicerae Japinicae Flos was selected as an example to elucidate the preparation and quality evaluation of Chinese single herbal medicine decoction. Twelve batches of representative Lonicerae Japinicae Flos were collected, UPLC fingerprints were established, and the chemical structures of main peaks were identified with UPLC QTOF-MS and standard compounds. The main components in the decoction are organic acids and iridoids. The extract rate of the standard decoction was (34.2+/-2.9)% and the transfer rate is (78.6+/-8.4)% in the form of chlorogenic acid, within the range of 75%-125% of mean. This paper established a method for the quality evaluation of standard decoction of Lonicerae Japinicae Flos and provided reference for the quality control method of terminal products from decoction of Lonicerae Japinicae Flos. PMID- 28994519 TI - [Establish quality evaluation method based on standard decoction of Danshen extract]. AB - The quality of Danshen extract granules on market is largely different from each other mainly due to the heterogeneous quality of raw materials of Salvia miltiorrhiza, various producing procedures and lack of good quality evaluation method. Formula granule and "standard decoction" have the same quality. In this paper, a systematic evaluation method for the quality of Danshen decoction was established from the perspective of "standard decoction", in order to explore the main factors affecting the quality uniformity of Danshen extract granules. Danshen standard decoction was prepared; then the fingerprint method was developed to determine the content of salvianolic acid B; and the main peaks in the fingerprint were identified with UPLC-QTOF/MS to clarify the chemical compositions of Danshen decoction. Three indexes were calculated to evaluate the stability of whole process, including the extraction ratio; transfer rate of index components and pH value. The results showed that the main components of Danshen decoction were phenolic acids, while the extraction rate, the transfer rate of salvianolic acid B and pH value were in a relatively stable level, and the similarity in the fingerprint of standard decoction was high, indicating that the preparation procedure was stable. The level of salvianolic acid B in the standard decoction was in a large range, which was mainly due to the difference in the quality of Salviae Miltiorrhizae Radix et Rhizoma. PMID- 28994520 TI - [Establish quality evaluation system for standard Ephedrae Herba decoction]. AB - To establish the quality control methods for the standard decoction of Ephedrae Herba, and provide the reference for quality evaluation method of all Chinese herbal medicine decoction.Standard decoction of Ephedrae Herba was prepared, and UPLC-UV fingerprint was established to determine the total contents of ephedrine and pseudoephedrine. Then UPLC-QTOF/MS was used to confirm the major common peaks in the fingerprint to clarify the main chemical constituents in the decoction. In addition, the stability of the process was evaluated by calculating the parameters such as the extraction ratio, transfer rate of the index components and the pH values.In the decoction of Ephedrae Herba, the total average concentration of ephedrine and pseudoephedrine was (2.11+/-0.70) g*L-1; the similarities of all the fingerprints were more than 0.85; there were 10 major common peaks in the fingerprint, including alkaloids, flavonoids and organic acids; the extraction ratio was (17+/-3.2)%, and the overall transfer rate of ephedrine and pseudoephedrine was (32.4+/-8.1)%.The method for evaluating the quality of standard decoction of Ephedrae Herba was established in this article, providing reference for the quality control of products which were stemmed from the water extract of Ephedrae Herba. PMID- 28994521 TI - [Research on Glycyrrhizeae Radix standard decoction]. AB - Fifteen batches of Glycyrrhizeae Radix standard decoction were prepared for determination of the content of the glycyrrhizic acid and liquiritin, then the transfer rate and the extract rate were calculated and a method was established to analyze the fingerprint by HPLC. According to the measurement of 15 batches of samples,the transfer rate of the glycyrrhizic acid and liquiritin were 59.4% 87.4% and 49.8%-78.9% with extract rate of 29.9%-38.9%. Moreover,10 common chromatographic peaks were determined based on their fingerprint by using similarity evaluation system for chromatographic fingerprint of traditional Chinese medicine (TCM)(2012A) .The similarity results of 15 batches of samples were analyzed and compared,and the results showed that the similarity was all higher than 0.9. Fifteen batches of samples,prepared by a standard method,have stable quality and the high similarity.The method displayed good precision,stability and repeatability in fingerprint analysis. Therefore,this study can provide a reference for the quality control of Glycyrrhizae Radix dispensing granules. PMID- 28994522 TI - [Moderation-integrated-balance presupposition of Chinese medicine compound and pharmacological problems in traditional Chinese drug research]. AB - The moderation-integrated-balance presupposition (MIBP) of Chinese medicine compound was first proposed in this paper based on the review of function characteristics and action principles of Chinese medicine compound. Furthermore, the pharmacological problems of traditional Chinese drug research were discussed in details. The results were of important value in accelerating the transformation of traditional Chinese medicine compound, and constructing the new drug innovation and review system for traditional Chinese medicine. PMID- 28994523 TI - [Discussion on clinical problems about bases of new drug of traditional Chinese medicine development]. AB - In view of the industry lacking of sufficient analyses on the bases of project establishment about the new drugs of traditional Chinese medicine(TCM) during their applying for the clinical research, from the perspective of clinical evaluation, this paper reviewed and analyzed the present situation and development paths of new drugs of TCM in recent years. Through the analyses of the rationality of formulations, human use experiences and clinical studies, the paper puts forward the countermeasures to solve these difficulties during the technical evaluation of new drugs of TCM in order to improve the new drugs' clinical research. PMID- 28994524 TI - [Clinical value evaluation of Chinese herbal formula in context of multi-omics network]. AB - Clinical value evaluation is the key issue to solve the problems such as high repetition rate, fuzzy clinical positioning, broad indications and unclear clinical values in Chinese herbal formula(Chinese patent medicine). By analyzing the challenges and opportunities of Chinese herbal formula in clinical value evaluation, this paper introduced a strategy of multi-omic network analysis. Through comparative analysis of three stroke treatment formulas, we suggested their different characteristic advantages for variant symptoms or phenotypes of stroke, which may provide reference for rational clinical choice. Such multi-omic network analysis strategy may open a unique angle of view for clinical evaluation and comparison of Chinese herbal formula. PMID- 28994525 TI - [Discussion on efficacy evaluation thought and method for innovation medicine of Chinese herbal compound formula based on clinical application characteristics]. AB - The Chinese herbal compound formula preparation was made based on theory of Chinese medicine, which was confirmed by long period clinical application, and with multi-compound and multi-target characteristics. During the exploitation process of innovation medicine of Chinese herbal compound formula, selecting and speeding up the research development of drugs with clinical value shall be paid more attention, and as request of rules involved in new drug research and development, the whole process management should be carried out, including project evaluation, manufacturing process determination, establishment of quality control standards, evaluation for pharmacological and toxic effect, as well as new drug application process. This reviews was aimed to give some proposals for pharmacodynamics research methods involved in exploration of Chinese herbal compound formula preparation, including: 1the endpoint criteria should meet the clinical attribution of new drugs; 2the pre-clinical pharmacodynamics evaluation should be carried on appropriate animal models according to the characteristics of diagnosis and therapy of Chinese medicine and observation indexes; 3during the innovation of drug for infants and children, information on drug action conforming to physiological characteristics of infants and children should be supplied, and the pharmacodynamics and toxicology research shall be conducted in immature rats according to the body weight of children. In a summary, the clinical application characteristics are the important criteria for evaluation of pharmacological effect of innovation medicine of Chinese herbal compound formula. PMID- 28994526 TI - [Research progress of Baizhu Shaoyao powder in treating ulcerative colitis]. AB - Ulcerative colitis is a chronic, nonspecific and complex intestinal disease. The current clinical treatment guideline of this disease recommends a variety of options with oral western medicines, such as aminosalicylic acids, glucocorticosteroids, and immunosuppressors. However, due to their unstable therapeutic effects, high toxicities, and strong drug dependence, they are not suitable for long-term administration. Baizhu Shaoyao powder, a traditional Chinese medicinal prescription, is clinically and commonly used for tonifying spleen and softening liver as well as eliminating dampness and relieving diarrhea. Recent researches suggest that Baizhu Shaoyao powder has significant effect in the treatment of ulcerative colitis. This article reviewed the research progress on the curative effect and action mechanism of Baizhu Shaoyao powder in treating ulcerative colitis, and provided the ideas and directions for its further research in future. PMID- 28994527 TI - [Advance on quality control of toad venom and its key influence factors]. AB - Toad venom (Chansu) is prepared from the dried secretion of Bufo bufo gargarizans or B. melanostictus. It is not only one of the famous and expensive traditional Chinese medicines(TCMs) from animal origin, but also one of 28 kinds of toxic TCMs to be required for special management issued by the State Council of the People's Republic of China. Chansu contains the rich bufadienolides and indole alkaloids, and displays various bioactivity including cardiotonic, anti-tumor, analgesia, and local anesthesia. Based on the published references in the recent years, the advance on the identification of adulterants and quality evaluation as well as the influence factors on the quality of toad venom was summarized to improve the quality standards and promote the level of quality control of toad venom and its preparations. PMID- 28994528 TI - [Research progress on regulation effect of Panax notoginseng saponins on mitochondria]. AB - Mitochondria is the key energy source of cells and plays an important role in energy synthesis and release, and maintenance of cellular functions. As the most important active ingredients in Chinese medicine pseudo-ginseng, Panax notoginseng saponins(PNS) have pharmacological effects on protecting against thrombosis, dilating blood vessels, lowering the blood pressure, anti inflammation, and antioxidant, etc. Domestic and foreign studies have shown that PNS participates in regulating mitochondrial energy metabolism, oxidative stress, biosynthesis, apoptosis, mitophagy and the status of membrane channels. Therefore, the mitochondria is one of the important targets of PNS. In this paper, the regulation effects of P. notoginseng saponins on mitochondria were reviewed. PMID- 28994529 TI - [Soil improvement promoted micro-ecology of farmlands for ginseng cultivation]. AB - This study has revealed the change of the soil micro-ecology of farmlands, which used for ginseng cultivation, brought by comprehensive soil improvement. The process of soil improvement was described as follows: soil was sterilized using trichloronitromethane, and then perilla seeds were planted. After growing up, the perillas were turned over into the field and fermented, then organic fertilizer was added. Rotary tillages were carried out during the intervals. Physical and chemical properties of treated soil were measured, as well as microbial diversity, which was illustrated using 16s high through-put sequencing. The survival rate and growth data of ginseng seedlings were recorded. The analysis showed that after improvement, the soil organic matter content was increased and soil bulk density was decreased, compare to the controls, and the fertility in 0 20 cm of soil layer was increased in the treatment. Additionally, the soil microbial diversity was changed greatly. In detail, alpha diversity of the soil decreased after soil improvement while the beta diversity increased. In order to verify the achievement of soil improvement, ginseng seedlings were planted. Compared to the untreated land blocks, the survival rate of ginseng on improved blocks was increased up to 21.4%, and the ginseng physiological index were all better than the controls. Results showed that comprehensive soil improvements including soil sterilization, green manure planting and organic fertilization application effectively improved the soil micro-ecology in farmlands. This study will pave the way for the future standardization of ginseng cultivation on farmlands. PMID- 28994530 TI - [Regional stability analysis of Pseudostellariae Radix new variety "Shitai No.1"]. AB - To provide guidance for certification, popularization and application of Pseudostellariae Radix new variety, the regional adaptation and stabilities of "Shitai No.1" were evaluated. The "Qian taizishen No.1" and "SB-C" varieties (strains) were used as the control varieties. The agronomic, medicinal material traits and medicine quality were used as evaluation index to compare the phenotypic difference of the three varieties (strains) in four planting areas. Compared to the control varieties, 10 agronomic traits of "Shitai No.1" had the smallest coefficient of variation among the 18 agronomic traits, and other 8 agronomic traits placed the middle level. Among 8 medicinal material traits and medicine quality indicators, the coefficient of variation of different regions of the extract content, pseudostellarin B content, the number of 50 g root tuber, the plant medicinal materials weight and weight of single root of "Shitai No.1" were the smallest compare to other varieties (strains). It could be divided into three groups based on the phenotypic difference of the three varieties (strains) in four planting areas. The "Shitai No.1" was classified as one group, while the "Qian taizishen No.1" and "SB-C" had cross clustering. The regional stability of several index about agronomic traits, medicinal material traits and medicine quality of "Shitai No.1" were better than that of the control varieties (strains). "Shitai No.1" was suitable for planting, popularization and application in the appropriate ecological areas of Guizhou province. PMID- 28994531 TI - [Cloning, subcellular localization, and heterologous expression of ApNAC1 gene from Andrographis paniculata]. AB - Andrographis paniculata is widely used as medicinal herb in China for a long time and andrographolide is its main medicinal constituent. To investigate the underlying andrographolide biosynthesis mechanisms, RNA-seq for A. paniculata leaves with MeJA treatment was performed. In A. paniculata transcriptomic data, the expression pattern of one member of NAC transcription factor family (ApNAC1) matched with andrographolide accumulation. The coding sequence of ApNAC1 was cloned by RT-PCR, and GenBank accession number was KY196416. The analysis of bioinformatics showed that the gene encodes a peptide of 323 amino acids, with a predicted relative molecular weight of 35.9 kDa and isoelectric point of 6.14. To confirm the subcellular localization, ApNAC1-GFP was transiently expressed in A. paniculata protoplast. The results indicated that ApNAC1 is a nucleus-localized protein. The analysis of real-time quantitative PCR revealed that ApNAC1 gene predominantly expresses in leaves. Compared with control sample, its expression abundance sharply increased with methyl jasmonate treatment. Based on its expression pattern, ApNAC1 gene might involve in andrographolide biosynthesis. ApNAC1 was heterologously expressed in Escherichia coli and recombinant protein was purified by Ni-NTA agarose. Further study will help us to understand the function of ApNAC1 in andrographolide biosynthesis. PMID- 28994532 TI - [Study on identification of Dendrobium officinale and related species by bidirectional PCR amplification of mismatched and specific alleles]. AB - Based on rDNA ITS sequences of Dendrobium officinale and the other 69 species of Dendrobium, a pair of dismatched allele-specific diagnostic primers, TPSH-AS1F and TPSH-AS1R were designed to authenticate D. officinale from the other species. Thebidirectional PCR amplification were performed using the diagnostic primers with the total DNAs of the original plants or processing products as a template. When the annealing temperature was raised to 60 C, only the template DNA of D. officinale could be amplified whereas the diagnostic PCRs of the other Dendrobium species were all negative. Compared with the other authentification methods, the bidirectional PCR amplifications is not only simpler and time-saving but practical and effective. PMID- 28994533 TI - [Identification and phylogenetic analysis of endophytic fungi isolated from Scrophularia ningpoensis]. AB - The endophytic fungi from root, main stem, branch and leaf of Scrophularia ningpoensis were isolated and identified from Wulong and Chongqing, and the population diversity analysis and phylogenetic analysis were followed. The result indicated that, as to population diversity index, S. ningpoensis from Wulong: leaf>main stem=branch>root, branch from Chongqing>branch from Wulong. Fifty-eight endophytic fungi were obtained, most of which were the pathogens of the plant. Colletotrichum was the prevailing genus, of which C. gloeosporioides and C. boninense were the prevailing strains. Leaf and seedlings might be the main path of infection. Endophytic fungi and pathogen might convert to each other, influenced by such factors as environment, genotype et al. PMID- 28994534 TI - [A new styrene dimer derivative from Litsea greenmaniana]. AB - A new styrene dimer derivative has been isolated from the branch of Litsea greenmaniana by column chromatography over silica gel and Sephadex LH-20, as well as semi-preparative HPLC. Its structure was identified by spectroscopic data analysis (MS, UV, IR, 1D and 2D NMR) as (E)-2,4-bis(p-hydroxyphenyl)-2-butenol, named as listeanol. At a concentration of 1*10-5 mol*L-1, compound 1 was inactive in the assays, including cytotoxicity against human tumor cell lines (HCT-8, Bel 7402, BGC-823, A549 and A2780), antioxidant activity in Fe2+-cystine-induced rat liver microsomal lipid peroxidation, neuroprotective activity against serum deprivation or glutamate induced neurotoxicity in cultures of PC12 cells, and the inhibitory activity against protein tyrosine phosphatase 1B (PTP1B). PMID- 28994535 TI - [Antitumor activity and structure-activity relationship of seven lanostane-type triterpenes from Fomitopsis pinicola and F. officinalis]. AB - Seven lanostane-type triterpenes including fomitopsin C(1),3-keto dehydrosulfurenic acid(2),dehydroeburiconic acid(3),3-acetyloxylanosta-8, 24-dien 21-oic acid(4),pinicolic acid A(5),trametenolic acid B(6),and eburicoic acid(7),were isolated from the fruitbodies of Fomitopsis pinicola and F. officinalis. In vitro assay, all compounds were evaluated against MCF-7, HeLa, HepG2 and A549 cells lines using the MTT assay and the structure-activity relationship of antitumor activity was discussed. The results showed that the seven compounds were more sensitive to MCF-7 cells.The IC50 value for MCF-7 was 2<5<4<1<3<6<7. H22 tumor mouse model was used to assay compounds 2, 3, 4 and 5 in vivo. Compounds 2 and 4 had obvious effect and the necrosis area and measurement were positively correlated. The results showed that compounds 2, 4 and 5 had significant antitumor activities at a dose of 20 mg*L-1 with 65.31%, 56.71%, 58.72% suppression, respectively, approaching to CTX group with 69.19% suppression in subcutaneous H22-implanted mice.The results showed that these compounds had significant against the expression of VEGF, cytokines IL-4 and IFN gamma tumor, additionally, the structure-activity relationship of lanostane-type triterpenes indicated that the acetoxyl or carbonyl at C-3 and hydroxy at C-15 can enhance the antitumor activity. PMID- 28994536 TI - [Changes of chemical constituents in Rubiae Radix et Rhizoma before and after carbonized by UPLC-Q-TOF-MS method]. AB - In order to explore the effect on chemical constituents after carbonized, the changes of chemical constituents in raw and carbonized Rubiae Radix et Rhizoma were analyzed by UPLC-Q-TOF-MS. The research also used principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA) for data statistics to find out the main differences on components before and after carbonized. The accurate m/z values of Q-TOF-MS and Q-TOF-MS-MS fragments were applied to identify the structures. The results showed that 6 more discrepant constituents were existed between raw and carbonized Rubiae Radix et Rhizoma. Three constituents were selected as the main discrepant components according to the peak area (276 nm) and identified, as lucidin, xanthopurpurin and 1,3,6-trihydroxy-2-methylanthraquinone. After carbonized, contents of xanthopurpurin and 1,3,6-trihydroxy-2-methylanthraquinone were observably increasing, while lucidin was obviously decreasing. They could be used as the chemical markers for the differentiation between raw and carbonized Rubiae Radix et Rhizoma. The results of this experiment played an important role in the study of processing principle of carbonized Rubiae Radix et Rhizoma. It also provided important evidences for the interpretation of effective material based on carbonized Rubiae Radix et Rhizoma. PMID- 28994537 TI - [Simultaneous determination of eleven components in Ginkgo biloba leaves by high performance liquid chromatography method]. AB - To study Ginkgo biloba leaves in different producing area, we establish an HPLC method for the simultaneously determination of seven flavonoids glycosides and four biflavonoids in G. biloba leaves. The analysis was performed on an Agilent ZORBAX SB-C18 column(4.6 mm*250 mm, 5 MUm) wich acetonitrile, and 0.4% phosphoric acid as mobile phase at flow rate of 1 mL*min-1 in a gradient edution, and the detection was carried out at 254 nm.The calibration curves of the seven flavonoids glycosides and four biflavonoids had a good linearitiy with good recoveries. The established HPLC method is simple, rapid, accurate, reliable, and sensitive, and can be applied to the identification and quality control of G. biloba leaves. PMID- 28994538 TI - [Effects of pure total flavonoids from Citrus changshan-huyou on blood lipid metabolism in hyperlipidemic rats]. AB - To observe and investigate the effects and mechanisms of the pure total flavonoids from Citrus changshan-huyou(PTFC) on blood lipid metabolism in hyperlipidemic rats. SD rats were fed with high fat diet for 4 weeks to induce hyperlipidemic rats model, meanwhile three dosages (50, 100, 200 mg*kg -1*d -1) of PTFC were administrated intragastrically for 4 weeks respectively.After 2 weeks of modeling, their tail blood was taken and serum TC, TG, and HDL-C levels were detected by biochemical method and their body weight was measured. After 4 weeks of modeling, their body weight was measured and liver weight was measured, then the levels of TC, TG, HDL-C, LDL-C, ALT, AST, MDA and SOD in serum were detected to calculate lipid comprehensive index(LDL-C/HDL-C and LDL-C/TC ratios) and atherogenic index(AI); in addition, MDA and SOD levels were detected by biochemical method. The hitopathological changes of the liver tissues were observed by HE staining; the protein expression levels of PPAR-alpha, Lpl, and Lipc were detected by ELISA; and the mRNA expression levels of PPAR-alpha in the liver tissue were detected by Real-time PCR. The results showed that gavage administration of the PTFC significantly decreased the body weight, liver weight, liver index, serum ALT and AST activities, the levels of serum TC, TG, LDL-C, LDL C/HDL-C, AI and increased serum HDL and LDL/TC level. Moreover, the PTFC significantly enhanced SOD activity and decreased the concentration of MDA in serum and liver tissue. Further mechanism investigation indicated that PTFC inhibited serum lipid accumulation by increasing the expressions PPAR-alpha, Lpl, Lipc protein and PPAR-alpha mRNA of the liver tissues. PTFC could actively regulate blood lipid metabolism by ameliorating hepatic function, improving the body's antioxidant capacity, lowering levels of oxidative stress, as well as positively regulating the expression levels of PPAR-alpha, Lpl, Lipc protein and PPAR-alpha mRNA of the liver tissues in rats. PMID- 28994539 TI - [Siwu decoction improves iron deficiency anemia in infant rats and regulates iron metabolism]. AB - To investigate the effect of Siwu decoction on improving iron deficiency anemia in infant rats and observe its regulatory effects on iron metabolism. SD rats were fed with low iron fodder for 2 weeks, and then the rats with hemoglobin level less than 75 g*L -1 were screened out and randomly divided into model group, Ferrous succinate 50 mg*kg -1 group, Siwu decoction 4 g*kg -1, 8 g*kg -1 and 16 g*kg -1 groups. After 4 weeks' gavage administration, Wright-Giemsa's staining of blood smear and HE staining of the livers were conducted, and all rats were tested for blood routine, serum iron, total iron binding capacity, serum ferritin, serum hepcidin and liver hepcidin. The expression levels of liver ferritin, transferrin and transferrin receptor 1 were also detected. The results showed that as compared with normal group, the activity level of model group was decreased, and the color and lustre of auricles and toes were pale white; the number of red blood cells was decreased; the volume was smaller, with an increased zone of central pallor; the body weight and blood routine parameters were decreased significantly; the livers were pale red, and the hepatic cords around thecentral veins were unclear and misaligned; the serum iron, serum ferritin, liver iron levels and the expression of liver ferritin were decreased significantly; the total iron binding capacity, serum hepcidin, liver hepcidin, the expression levels of liver transferrin and transferrin receptor 1 were significantly increased, indicating successful establishment of models. As compared with the model group, activity was increased in Siwu decoction group; the color and lustre of auricles and toes were ruddy; the number of red blood cells was increased; the volume was larger, with a decreased zone of central pallor; the body weight and blood routine parameters were increased significantly; the livers were red, hepatic cords around the central veins were clear and aligned;the serum iron, serum ferritin, liver iron levels and the expression of liver ferritin were significantly increased, the total iron binding capacity, serum hepcidin, liver hepcidin, the expression of liver transferrin and transferrin receptor 1 were decreased significantly. The results demonstrated that Siwu decoction had a certain effect on improving iron deficiency anemia in infant rats, and the mechanism may be associated with the regulatory effect of hepcidin iron metabolism. PMID- 28994541 TI - [Effect of Chinese herb chicory extract on expression of renal transporter Glut9 in rats with hyperuricemia]. AB - Sixty SD male rats were randomly divided into normal group, model group, benzbromarone group(20 mg*kg-1*d-1), chicory extract high dose, middle dose and low dose groups (5, 7.5, 10 g*kg-1*d-1). The rats in normal group were given with water, and the rats in other groups were given with 10% fructose solution to establish hyperuricemia models. All the rats were sacrificed on the 42th day. Then their serum uric acid(SUA), serum creatinine(CRE), urea nitrogen(BUN) and urinary uric acid(UUA) levels were detected to calculate the clearance rate of uric acid in kidney(CUA). Meanwhile, the protein and gene expression levels of renal glucose transporter family member 9(Glut9) were detected by immunohistochemical and Real-time quantitative reverse transcription-polymerase chain reaction(RT-qPCR) methods. The effects of Chinese herb chicory extract on expression of renal Glut9 and decreasing uric acid were explored in this study, and the results showed that chicory extract could reduce SUA level in rats with hyperuricemia, increase renal CUA, decrease the protein expression of renal Glut9, inhibit uric acid re-absorption in kidney, and thus promote renal uric acid excretion. PMID- 28994540 TI - [Protective effect of Shuyu Yiban decoction on atherosclerosis in rats induced by chronic unpredictable mild stress]. AB - Shuyu Yiban decoction(SYYB) has significant effect in treating the patients with coronary heart disease combined with chronic psychological stress. In this study, in order to observe the effects of SYYB on early formation of atherosclerosis(As) and inflammation response induced by chronic psychological stress, high-fat diet+intraperitoneal injections of Vitamin D3 were given to establish As early lesion models, and based on these models, chronic unpredictable mild stress(CUMS) was used to observe whether the chronic psychological stress could increase coronary atherosclerotic lesions investigate the intervention effect of SYYB(6.6, 13.2, 26.4 mg*kg-1). The tail suspension test and novelty-feeding test were adopted to detectadrenocortico-tropic hormone(ACTH), cortisol(Cor) andnoradrenaline(NE) in serum and weigh thymus and adrenal gland, in order to assess the effects of SYYB on CUMS model rats. The pathological changes of vascular tissues in aortic arch were observed by using hematoxylin and eosin(HE) staining, and then the levels of triglycerides(TG), total cholesterol(TC) and high density lipoprotein(HDL-C) in serum were determined to assess effects of SYYB on As lesions. The effects of SYYB on the inflammatory response in As rats were assessed by detecting high-sensitivity C-reactive protein(hsCRP), interleukin-1beta(IL-1beta) and interleukin-6(IL-6) in serum. The results showed that as compared with the blank control group, TC and TG levels in As group were increased while HDL-C was markedly decreased; furthermore, the aortic wall was thickened in HE staining. Meanwhile, foam cells were formed, and the behavioral assessment and serum stress hormone test showed that there was a chronic stress response, indicating successful establishment of As+CUMS models in this study. The experiment demonstrated that SYYB could lower the levels of serum TC and TG, reduce foam cells, calcification and inflammatory cells infiltration. Moreover, SYYB could obviously lower levels of ACTH, Cor and NE and the As related inflammatory indicatorhs-CRP, IL-1beta and IL-6 in serum.These results indicated that SYYB had protective effect on chronic psychological stress induced in As rats, and the mechanism was associated with balancing the neuroendocrine-immune network system and regulating inflammation response. PMID- 28994542 TI - [Mechanism of Ezhu-containing serum in inhibiting expression of Shh and Gli1 in hepatic stellate cells]. AB - To explore the mechanism of Ezhu-containing serum in inhibiting the expression of sonic hedgehog(Shh) and glioma-associated oncogene homolog-1(Gli1) in hepatic stellate cells(HSCs) induced by leptin. Twenty sprague-dawley (SD) rats were randomly divided into 2 groups (n=10), and given Ezhu-decoction and physiological saline by gavage for 10 days to prepare drug-containing serums. The HSCs during the exponential growth phase were divided into 7 groups: blank control group, model group, hedgehog pathway inhibitor(cyclopamine) group, Ezhu group, Ezhu and cyclopamine group, hedgehog pathway agonost(pumorphamine) group, Ezhu and purmorphamine group. HSCs were cultured in vitro and induced with 100 MUg*L -1 leptin(except for the blank control group), then treated separately with the corresponding drugs for 24 hours. After the cells were collected, HSCs proliferation was detected using MTT colorimetric assay; the expressions of Shh and Gli1 were determined by PT-PCR, Western blot and immunofluorescence, respectively. The expressions of Shh and Gli1 were significantly increased after the HSCs of rats were induced by leptin (compared with the blank control group, P<0.01). After being interfered with Hh pathway inhibitor (cyclopamine) and Ezhu containing serum, the expressions of Shh and Gli1 were decreased significantly(compared with the model group, P<0.01). After Ezhu-containing serum was used to interfere the Hh pathway inhibitor group, the mRNA and protein expressions of Shh and Gli1 were decreased significantly(compared with the model group, P<0.01). After Ezhu-containing serum was used to interfere the purmorphamine group, the mRNA and protein expressions of Shh and Gli1 decreased significantly(compared with the purmorphamine group, P<0.01). Ezhu-containing serum plays an important role in inhibiting HSCs activation by taking part in hedgehog signaling pathway, so as to regulate the expression of Shh and Gli1 in leptin-induced HSCs and then inhibit liver fibrosis. PMID- 28994543 TI - [Effect of Tongxie Yaofang on endogenous metabolites in serum of IBS model rats]. AB - To evaluate the effect of Tongxie Yaofang on cardiac endogenous metabolism in irritable bowel syndrome(IBS) rats by using metabolomics method, find its potential biomarkers, analyze the metabolic pathways, and explore the pharmacological effects, mechanisms of action and syndrome essence of syndrome model. Forty Wistar rats were used to establish IBS models, and then randomly divided into four groups: model control group and Tongxie Yaofang treatment groups (high, medium, low dose). Another 10 rats were used as normal group. The rats in Tongxie Yaofang-treated(low, medium and high dose) groups were orally administrated with Tongxie Yaofang extracts once a day for 2 weeks, respondingly with the doses of 0.203,0.406,0.812 g*mL-1. The rats in normal group and model control group were given with equal volume of saline once a day for 2 weeks. On the 0 and 15th days, serum was collected and each sample extract was analyzed by UPLC-Q-TOF-MS. Eight potential biomarkers were identified and 8 major metabolic pathways were found to be related with IBS diseases neurotransmitter metabolism, inflammatory immunity, brain function and energy metabolism, etc. Tongxie Yaofang had certain pharmacological effects on IBS, and its mechanism may be related to serotonergic synapse, tryptophan metabolism, cysteine and methionine metabolism, glycerophospholipid metabolism, nicotinate and nicotinamide metabolism and so on, which might be the biological basis of IBS liver-spleen deficiency syndrome. PMID- 28994544 TI - [Effect of Shuxuetong injection on anticoagulant effect of warfarin in rats]. AB - To explore the effect of Shuxuetong injection on the pharmacodynamics and pharmacokinetics of warfarin in rats, and to provide reference for rational drug use. In studies on the single dose of warfarin, Wistar rats were randomly divided into four groups: blank control group(group A), Shuxuetong injection group(group B), warfarin control group(group C), and warfarin+Shuxuetong injection group(group D). In studies on the steady state of warfarin, Wistar rats were randomly divided into warfarin control group(group E) and warfarin+Shuxuetong injection group(group F). To investigate the pharmacodynamic effect of Shuxuetong injection on warfarin, prothrombin time(PT) and activated partial thromboplastin time(APTT) were measured by coagulation analyzer, and international normalized ratio(INR) was calculated. To investigate the pharmacokinetic effect of Shuxuetong injection on warfarin, the blood concentrations of S-warfarin and R warfarin were determined by UPLC-MS/MS combined with technology of chiral chromatographic column, and the related pharmacokinetic parameters were calculated accordingly. The results on the single dose of warfarin showed that Shuxuetong injection markedly increased PT, INR(P<0.01), and APTT(P<0.05). Meanwhile, when Shuxuetong injection was co-administrated with warfarin, it significantly increased PT, INR(P<0.01), and APTT(P<0.05) as compared with warfarin control group. In addition, increased pharmacokinetic parameters including Cmax, AUC0-t and AUC0-infinity, prolonged t1/2, and decreased CL/F were observed for S-warfarin and R-warfarin. The results of the steady state of warfarin suggested that Shuxuetong injection significantly increased PT and INR of warfarin(P<0.01), and elevated the plasma concentrations of S-warfarin and R warfarin when co-administrated with warfarin. These findings indicated that Shuxuetong injection had anticoagulant effect, and would produce pharmacodynamics synergistic action when it was co-administrated with warfarin. Shuxuetong injection also decelerated the metabolism of warfarin, and resulted in pharmacokinetics interaction. Therefore, Shuxuetong injection could significantly increase anticoagulant effect of warfarin, indicating that the combination use of these two drugs should be refrained in order to avoid the risk of bleeding in clinical application. If they need to be used in combination, special attention should be paid to ensure the safety of patients. PMID- 28994545 TI - [Analysis of varieties and standards of Composite medicinal plants used in Dai medicine]. AB - The study aims to analyze the varieties and standards of compositae medicinal plants used in Dai medicine. The results showed that there were 78 species (including varieties) compositae plants recorded in literatures, which belongs to 63 medicinal materials varieties. And 47 original plants (60.25%) were recorded in Chinese medicinal material standards. In those standards and literatures of Dai medicine, there are great differences in translated Chinese names, original plants, medicinal parts, and efficacy of medicinal plants. Therefore, the variety systematization and the quality standards of Dai medicine should be strengthened. PMID- 28994546 TI - [Variety systematization and research progress of Mongolian medicine "Bashaga"]. AB - Mongolian medicine is the traditional drug with the theory of Mongolian medicine and pharmacy as a guide, which made a great contribution to the survival and development of the Mongolian people. Mongolian medicine "Bashaga" faced the situations of origin is unclear, and clinical therapy is confused and so on. This paper summarizes the original plants and studies the species textual research and ethnopharmacology of Mongolian medicine "Bashaga". This paper intends to ensure authentic plant and provide comprehensive insight into the chemical constituents, pharmacology and application status of Mongolian medicine "Bashaga" to discuss the rationality of the confirmation in "Bashaga" authentic plant. PMID- 28994547 TI - [Explore molecular mechanism of Chinese herbs with promoting blood circulation and resolving phlegm effects on myocardial ischemia reperfusion injury based on correlation between microRNA and mtDNA]. AB - A large number of basic and clinical studies have shown that the Chinese herbs with promoting blood circulation and resolving phlegm effects could prevent and treat myocardial ischemia-reperfusion injury(MIRI) by regulating lipid metabolism. But its mechanism is not yet clear. The studies show that mitochondrial DNA (mtDNA), microRNAs and lipid metabolism participate in the whole process of MIRI and affect the prognosis. mtDNA mutation is the primary factor to cause myocardial ischemia and reperfusion myocardial cell damage. microRNAs aggravate or reduce MIRI injury by down-regulating or up-regulating related genes expression, while miR-33, as a key regulator of cholesterol transport, regulates lipid metabolism through CROT, PGC-1alpha, AMPK and other genes located in the mitochondria. There are less studies on correlation between miR-33 and mtDNA, microRNAs. Therefore, further studies on the correlation between miR-33 and mtDNA, microRNAs, as well as the discussions on whether the traditional Chinese medicine (TCM) with promoting blood circulation and resolving phlegm effects could target miR-33 to regulate lipid metabolism and inducemt DNA mutations or deletions, would have important significance for the prevention and treatment of MIRI. PMID- 28994548 TI - Chlamydia infection raises long-term risk of reproductive complications. PMID- 28994554 TI - Diagnosis and treatment of inflammatory bowel disease. AB - Patients with inflammatory bowel disease (IBD) may previously have received a diagnosis of irritable bowel syndrome and there may be a delay in making the correct diagnosis. This is particularly the case in patients with ileal Crohn's disease and those under 40. Diagnosis of IBD involves endoscopy and biopsy. Histology may not be available - for example in small bowel Crohn's disease - and in this situation, typical radiological appearances help make the diagnosis. Crohn's disease can affect any part of the gastrointestinal tract - most commonly the terminal ileum or colon. Perianal involvement is also common. Intestinal inflammation in Crohn's disease can extend transmurally. Ulcerative colitis almost always affects the rectum with a variable proximal extent and continuous distribution. Inflammation affects the mucosa only. Approximately 25% of people with IBD will have extra-intestinal manifestations of the disease, involving skin, eyes, joints or the liver. There is an increased risk of colorectal cancer in patients with ulcerative colitis estimated at 2% at 10 years, 8% at 20 years and 18% at 30 years. It is important to be aware of infection risk in IBD both due to the disease itself and the impact of treatment. Flu vaccination should be offered to patients with IBD. PMID- 28994553 TI - Improving the detection of coeliac disease. AB - The common presentation of coeliac disease has shifted from the historically classical symptoms of malabsorption in childhood to non-classical symptoms in adulthood such as irritable bowel syndrome-type symptoms, anaemia, chronic fatigue, change in bowel habit, abdominal pain and osteoporosis. A combination of coeliac serology and duodenal biopsy is required to diagnose coeliac disease in adults. Testing for IgA-tissue transglutaminase antibodies should be carried out as a first-line screening test. Advise patients to eat a gluten-containing diet for six weeks before their investigations to ensure the serological and histological results are not affected. A confirmatory duodenal biopsy is mandatory to ensure that patients are correctly diagnosed with coeliac disease. A lifelong strict gluten-free diet is the only effective treatment currently available. All patients should be referred to a specialist dietitian for guidance and support. Annual follow-up can begin when the disease is stable and patients are managing well on their diet. PMID- 28994555 TI - Have a high index of suspicion for meningitis in adults. AB - Bacterial meningitis and meningococcal sepsis are rare in adults. Any diagnostic delays with subsequent delay to treatment can have disastrous consequences. The decline in bacterial meningitis over the past few decades has not been accompanied by a reduction in case fatality rate which can be as high as 20% for all causes of bacterial meningitis and 30% in pneumococcal meningitis. The classic triad of neck stiffness, fever and altered consciousness is present in < 50% of cases of bacterial meningitis. Patients with viral meningitis also present with signs of meningism (headache, neck stiffness and photophobia) possibly with additional non-specific symptoms such as diarrhoea or sore throat. Suspected cases of meningitis or meningococcal sepsis must be referred for further assessment and consideration of a lumbar puncture. Most patients will fully recover. However, the sequelae of bacterial meningitis and meningococcal disease can be disabling. Many patients feel well at discharge and do not realise that they may not be able to return to all their normal duties and activities straightaway. Fatigue, headaches, sleep disorders and emotional problems are often reported in the weeks and months after discharge. PMID- 28994556 TI - Identifying patients with complex PTSD. AB - While the common perception of post-traumatic stress disorder (PTSD) is of an individual suffering from a single traumatic event, clinicians need to be aware of those people who have been exposed to multiple potentially traumatic events. Type 2 or complex trauma results from multiple or repeated traumatic events occurring over extended periods. Complex trauma is often associated with other adversity and stressors such as neglect, loss or deprivation. For many individuals these traumas occur at a developmentally vulnerable time with the perpetrator often in a caregiving role; thus the trauma incorporates a betrayal of trust. Disclosure can be a problem particularly with complex trauma such as sexual abuse or domestic violence, and is often incremental as trust with the clinician is formed. Patients who have experienced complex trauma should be assessed for the core symptoms of PTSD. In addition, patients should be assessed for disturbances in the three domains of emotional dysregulation, negative self concept and interpersonal disturbances. PMID- 28994557 TI - Increasing survival of metastatic breast cancer through locoregional surgery. AB - BACKGROUND: Surgery for the primary tumor in metastatic breast cancer is usually not recommended, assuming that local therapy provides no advantage. Recent reports suggest a survival improvement after locoregional treatment, but this is still controversial. We aimed to evaluate the effectiveness of locoregional treatment in primary metastatic breast cancer and to determine associated factors. METHODS: A retrospective analysis of 39 women with de-novo metastatic breast cancer at La Paz University Hospital, from January 2012 to June 2016, grouped by locoregional treatment (n=23) or not (n=16). Multivariate assessment of prognostic factors was performed using Cox regression analysis. RESULTS: Mean tumor size was 6 cm. Eighteen patients (46.2%) had multifocal tumors, 29 (74.4%) multicentric and 10 (25.7%) bilateral breast cancer. Eighteen patients (46.2%) had an oligometastatic disease and 21 (53.8%) multiorgan metastatic disease. The average time from diagnosis to surgery was 7.7 months, without delay in the start of systemic treatment compared to the no-surgery group. The main surgical procedure was mastectomy in 18 (78.3%) patients. Half of the patients survived 48 months (95% CI: 39-57). In the multivariate analysis, we have not detailed differences in survival by age, chemotherapy, neoadjuvancy, number of systemic treatment lines, radiotherapy, and tumor histology or grade. However, surgery (HR=0.2; 95% CI: 0.07-0.57) and high tumor burden (HR=2.96, 95% CI: 1.23-7.13) have acted as a protective and a risk factor respectively. CONCLUSIONS: Our cohort supports that locoregional treatment in selected patients with de-novo MBC significantly improved survival, so it might be considered in combination with systemic therapy. PMID- 28994558 TI - Flexible CO2 laser fiber: first look at the learning curve required in gynecological laparoscopy training. AB - BACKGROUND: The advent of flexible CO2 laser fiber to gynecology arena might represent a turning point in the use of laser energy on a large-scale basis in gynecological surgery. However, there might be some concerns regarding the degree of surgical skills required to use the flexible system. The purpose of our study is to evaluate whether flexible CO2 laser fiber is technically accessible. METHODS: Fourteen residents in Obstetrics and Gynecology without surgical experience attending laparoscopic box training with both flexible CO2 laser fiber and traditional line-of-sight CO2 laser using Lumenis AcuPulse Duo CO2 laser (Lumenis, Yokne'am Illit, Israel) were prospectively enrolled. Participants were tested at sequential time points on specific surgical tasks and results obtained with the flexible CO2 laser fiber and the traditional line-of-sight CO2 laser were compared. Results were compared by means of paired t-test and a two-tailed P value <0.05 was considered significant. RESULTS: Mean grading at the beginning of training were similar between flexible fiber and line-of-sight CO2 laser. At the end of training, significant improvement in surgical skills was obtained for both techniques, with a statistically significant higher grading for flexible fiber CO2 laser compared to line-of-sight CO2 laser. CONCLUSIONS: Our study found that residents without surgical experience show better skills with the flexible CO2 laser fiber delivery system compared to the standard line-of-sight CO2 laser system after a two-month training period with gynecological laparoscopic box. According to our results, flexible CO2 laser fiber delivery system is technically accessible and holds a potential in gynecological surgery. PMID- 28994559 TI - Spontaneous rupture of bilateral pelvic vessels following vacuum-assisted vaginal delivery. PMID- 28994560 TI - Epidemiology and pathogenesis of fulminant viral hepatitis in pregnant women. AB - INTRODUCTION: The pregnancy-associated immunological and hormonal changes may alter the immune response to infectious agents, including hepatitis viruses. Therefore, this phenomenon may affect the clinical course and the outcome of acute viral hepatitis in pregnant women. EVIDENCE ACQUISITION: For this reason, we have focused on epidemiological and pathogenetic aspects of the fulminant liver failure caused by acute viral hepatitis reviewing PubMED in April of 2017. EVIDENCE SYNTHESIS: Although all the viruses might cause a fulminant acute viral hepatitis in a pregnant woman, the large majority of fulminant failure reported in the literature had been related to hepatits E virus (HEV) mainly and had been concentrated in Indian subcontinent and some African areas, whereas the problem seems to be very low or absent in the remaining geographical areas. However, the rate of maternal mortality due to fulminant E hepatitis may vary inside the endemic areas of India and Africa, likely due to the circulation of HEV genotypes with different degree of virulence. The other hepatitis viruses have not been reported to cause a greater risk for fulminant hepatitis in pregnant women respect to non-pregnant ones, except Herpes simplex virus, that has been associated to some cases of fatal hepatitis in absence of a prompt antiviral therapy. CONCLUSIONS: AVH should be considered when the pregnant woman develop fever, abdominal pain, malaise, nausea and anicteric hepatic dysfunction. PMID- 28994561 TI - Urine protein-to-creatinine ratio: a point of care for the diagnosis of preeclampsia. AB - BACKGROUND: The aim of this study was to determine the correlation between the urine protein-creatinine ratio (UPCR) and the 24-hour urine protein excretion test (UPET), and to identify the optimal threshold values of UPCR for the diagnosis of preeclampsia and its severe form. METHODS: This prospective cohort study included 81 hypertensive pregnant patients who had a 24-h UPET and a UPCR tests. Two groups were created using a UPCR cut-off of 23.2 mg/mmol (40 negative UPCR, 41 positive UPCR). RESULTS: Forty-nine patients of were diagnosed with preeclampsia, and 23 of them had a severe disease. There was a significant correlation between UPCR and 24-h UPET. A cut-off UPCR value of 23.2 mg/mmol had an area under the curve (AUC) of 0.27, sensitivity of 89%, specificity 88%, positive predictive value 90%, a positive likelihood ratio (+LR) of 7.41 and a negative likelihood ratio (-LR) of 0.13 for the diagnosis of preeclampsia. UPCR value of 325 mg/mmol had an AUC of 0.841, and a sensitivity of 83%, specificity 81%, positive predictive value 81%, +LR of 4.4 and -LR of 0.2 for the diagnosis of severe preeclampsia. CONCLUSIONS: The UPCR test is highly correlated with the 24-h UPET. We propose a novel and sensitive cut-off for the diagnosis of preeclampsia by UPCR test. The UPCR test can be used for the identification of hypertensive patients with preeclampsia and severe disease. PMID- 28994562 TI - Can unexplained infertility be evaluated by a new immunological four-biomarkers panel? A pilot study. AB - BACKGROUND: Inflammation and oxidative stress are known to be triggering factors for a decrease of the pregnancy rate like maternal immunosuppression. Under these circumstances our study was performed to verify four immunological biomarkers (IMMUNOX Panel) in terms of incidence in a sine-causa infertile population and the overall pregnancy rate when the Panel was showing some non-physiologic values. METHODS: Sera of 86 women affected by unexplained infertility were screened for the IMMUNOX panel of biomarkers composed by: tumor necrosis factor alpha (TNF-alpha,) glycodelin (GLY), total oxidative status (TOS), and complement activity toxic factor (CATF). When at least one of the biomarkers tested was showing values outside the physiologic range, the woman was considered IMMUNOX Positive. RESULTS: The first data was indented to verify the incidence of the women with an IMMUNOX-positive panel. Results show that 19.8%, 18.6%, 25.6%, and 47.7% were IMMUNOX-positive for GLY, TNF-alpha, TOS and CATF respectively. The overall incidence of IMMUNOX-positive patients, with at least one biomarker positive was 70,9%. Subsequently we have analysed the correlation between IMMUNOX Panel positivity and the pregnancy rate. The pregnancy rate in a subgroup (N.=55) of the entire population tested (N.=86) was 2.9% and 36.6% for the IMMUNOX positive and IMMUNOX-negative patients respectively. CONCLUSIONS: Further validation studies are needed to prove that there is a correlation between unexplained infertility and immunological disorders screened by the IMMUNOX Panel, nevertheless our data shows that this diagnostic approach may be helpful to predict and to identify women at higher risk of IVF cycles failure. PMID- 28994563 TI - An update on the genetics of pre-eclampsia. AB - Pre-eclampsia is a progressive multisystem disorder that is exclusive to human pregnancy and defined as new hypertension presenting after 20 weeks with significant proteinuria. It is a multifactorial condition with a strong genetic component and several genes have been linked with this disorder. The main players implicated in the pathogenesis of pre-eclampsia include immune maladaptation, hemodynamics, endothelial function, thrombophilic disorders, oxidative stress and lipid metabolism. All of these mechanisms encompass genetic factors that might be responsible for the pathogenic changes taking place. Pre-eclampsia has been referred to as a primipaternity disease. A number of studies examined the contribution of paternal genes in pre-eclampsia. Although there is evidence that paternal genes significantly increase the risk of pre-eclampsia, there is still inconclusive evidence whether having the same partner is a protective factor. Gene expression, through imprinting and epistasis, also play an important role in the pathogenesis of this disorder. Pre-eclampsia remains a disease of theories. Despite the growing body of research exploring this complex disorder, the etiology of pre-eclampsia remains elusive and the struggle is still ongoing to find an effective predictive test that can detect this disorder at an early stage where intervention can prevent the progression of the disorder. Research is still ongoing. Prevention and early detection of pre-eclampsia remain the ultimate goal. PMID- 28994564 TI - Targeted therapy for ovarian cancer: the rapidly evolving landscape of PARP inhibitor use. AB - INTRODUCTION: Poly(ADP-ribose) polymerase (PARP) inhibitors are a targeted therapy option for ovarian cancer. The goal of this review was to organize and summarize the clinical trials evaluating PARP inhibitor therapy in ovarian cancer as monotherapy, maintenance therapy after partial or complete remission to therapy or as a part of a combination regimen. EVIDENCE ACQUISITION: PubMed, ClinicalTrials.gov, data from the United States Food and Drug Administration (US FDA) and proceedings from scientific conferences were searched for published and unpublished data pertaining to clinical trials and approvals of PARP inhibitor use in ovarian cancer. EVIDENCE SYNTHESIS: There have been 36 published phase 1, 2 and 3 studies evaluating the use of olaparib, niraparib, veliparib and rucaparib in ovarian cancer. Olaparib and rucaparib have been approved by the US FDA as monotherapy for advanced recurrent ovarian cancer. Niraparib and olaparib have been approved by the US FDA for maintenance therapy after partial or complete remission in recurrent ovarian cancer. There are currently ten phase 3 trials evaluating PARP inhibitors at various timepoints in ovarian cancer therapy including at the time of primary adjuvant therapy, as maintenance therapy after primary chemotherapy, as monotherapy for recurrent cancer and as maintenance therapy after chemotherapy for recurrence. CONCLUSIONS: The landscape of PARP inhibitor use for ovarian cancer is rapidly evolving and PARP inhibitors have become more available as a targeted therapy option for ovarian cancer treatment. PMID- 28994565 TI - Research on the correlation between MMP gene polymorphism and susceptibility to cervical cancer in Chinese women. PMID- 28994566 TI - Sorbitol malabsorption in patients with abdominal discomfort. AB - BACKGROUND: The role of sorbitol malabsorption in patients with functional abdominal discomfort has not been finally clarified yet. Therefore, aim of this study was to evaluate the clinical significance of sorbitol malabsorption, diagnosed by sorbitol hydrogen breath testing in these patients. METHODS: Data of all patients referred to our hospital for hydrogen breath testing between May 1st, 2013 and December 31st, 2014 were retrospectively collected and analyzed. Patients with confirmed sorbitol malabsorption completed a symptom-based questionnaire before and after nutritional counseling. RESULTS: Five hundred and ten patients with functional abdominal discomfort (65.5% female, 34.5% male; mean age 45+/-16.4 years) were referred to our hospital for hydrogen breath testing. H2-sorbitol breath tests were performed in 252 of these patients. In 122 of them (48%), sorbitol-malabsorption was diagnosed. In 66 of these patients (54%), the results of the symptom-based questionnaire showed a significant improvement of the frequency of abdominal discomfort (P<0.001) and of the influence of these symptoms on daily life (P<0.001) after sorbitol testing/nutritional counseling. CONCLUSIONS: Sorbitol malabsorption is a common finding in patients with functional abdominal discomfort. Dietary intervention positively affects abdominal symptoms in these patients. PMID- 28994567 TI - Underwater endoscopic mucosal resection: an alternative treatment for large colorectal polyp removal. AB - BACKGROUND: Large sessile/flat colonic polyps are traditionally removed by lift polypectomy. Underwater endoscopic mucosal resection (UEMR) is a novel technique where air is suctioned out and replaced by water to decompress the colon so that the flat lesions assumes a more polypoid shape facilitating its removal with the standard snare resection. We report the feasibility and safety in our series of patients utilizing this technique. METHODS: A retrospective, observational study of all patients who underwent removal of large colonic polyps (>10 mm) over a period of 3 years (January 2012 to January 2015) at a tertiary care center by UEMR were included in the study. RESULTS: A total of 102 polyps were removed in 93 adult patients using UEMR. The mean age of patients was 64.7+/-9.7 years. The average number of polyps per patient was 1.84+/-1.3 with a range of 1-7. The range of the polyp size was 10 to 60 mm. The mean size of the polyp was 20.4+/ 9.4 mm, median size 26.9+/-9.4 mm. Ninety-two (90.2%) were removed in piecemeal fashion and ten (9.8%) were removed en bloc. Delayed bleeding occurred in seven (9.7%) patients. CONCLUSIONS: In this largest series on UEMR, we report the feasibility and safety of this procedure. Future randomized trials comparing this technique versus standard lift polypectomy technique will further elucidate the benefit of one over other. PMID- 28994568 TI - Management of H1N1 influenza infection in asthmatic patients. PMID- 28994569 TI - Carbon-coated self-expandable stents in patients with atherosclerotic iliac artery disease. AB - BACKGROUND: The aim of this study was to evaluate the safety and effectiveness of carbon-coated self-expandable stents in the revascularization of atherosclerotic iliac artery lesions. METHODS: Between January 2012 and June 2016 54 carbon coated self-expandable stents (Easy HiFlype and Easy Flype; manufactured by CID S.p.A., a member of Alvimedica Group, Istanbul, Turkey) in 40 patients were implanted in our Center. Early and 2-year outcomes have been evaluated in terms of major morbidity, mortality, primary patency, primary assisted patency, secondary patency, absence of target lesion restenosis (TLR), healing of the lesions/relief of symptoms, and limb salvage. RESULTS: The patients were predominantly males (32/40, 80%) with a mean age of 71 years (range 46-94). One patient (2.5%) had a documented nickel allergy. Mean duration of follow-up was 13.9 months (range 1-48). At 30 days no patient died and 1 patient underwent surgical revision of percutaneous femoral access. The estimated 2-year primary patency, primary assisted patency, secondary patency, absence of TLR, and limb salvage were 92.8%, 93.1%, 95.7%, 79.5%, and 100%, respectively. At univariate analysis none of the pre- or intra-operative factors significantly affected the primary and primary assisted patency rates. Secondary patency was significantly affected by absence of post-stent balloon dilatation (P=0.003). Absence of TLR was significantly affected by age more than 80 years (P=0.01) and common iliac artery lesions (P=0.02). These significances were confirmed at Cox regression analysis. CONCLUSIONS: Use of carbon-coated self-expandable stents in atherosclerotic iliac lesions was safe and effective. At 2 years, the patency rates and the absence of TLR were encouraging. Post-stent balloon dilatation should be recommended in all cases. Older patients and common iliac artery lesions were risk factors for restenosis in the mid-term period. PMID- 28994570 TI - Clustering of Cyclodextrin-Functionalized Microbeads by an Amphiphilic Biopolymer: Real-Time Observation of Structures Resembling Blood Clots. AB - Colloidal particles can be induced to cluster by adding polymers in a process called bridging flocculation. For bridging to occur, the polymer must bind strongly to the surfaces of adjacent particles, such as via electrostatic interactions. Here, we introduce a new system where bridging occurs due to specific interactions between the side chains of an amphiphilic polymer and supramolecules on the particle surface. The polymer is a hydrophobically modified chitosan (hmC) while the particles are uniform polymeric microbeads (~160 MUm in diameter) made by a microfluidic technique and functionalized on their surface by alpha-cyclodextrins (CDs). The CDs have hydrophobic binding pockets that can capture the n-alkyl hydrophobes present along the hmC chains. Clustering of CD coated microbeads in water by hmC is visualized in real time using optical microscopy. Interestingly, the clustering follows two distinct stages: first, the microbeads are bridged into clusters by hmC chains, which occurs by the interaction of individual chains with the CDs on adjacent particles. Thereafter, additional hmC from the solution adsorbs onto the surfaces of the microbeads and an hmC "mesh" grows around the clusters. This growing nanostructured mesh can trap surrounding microsized objects and sequester them within the overall cluster. Such clustering is reminiscent of blood clotting where blood platelets initially cluster at a wound site, whereupon they induce growth of a protein (fibrin) mesh around the clusters, which entraps other passive cells. Clustering does not occur with the native chitosan (lacking hydrophobes) or with the bare particles (lacking CDs); these results confirm that the clustering is indeed due to hydrophobic interactions between the hmC and the CDs. Microbead clustering via amphiphilic biopolymers could be applicable in embolization, which is a surgical technique used to block blood flow to a particular area of the body, or in agglutination assays. PMID- 28994571 TI - Facile Coordination-Precipitation Route to Insoluble Metal Roussin's Black Salts for NIR-Responsive Release of NO for Anti-Metastasis. AB - A facile and general coordination-precipitation method is developed to synthesize insoluble metal Roussin's black salts (Me-RBSs) as a new type of NIR-responsive NORMs. The weak-field ligand coordination of metal+-RBS- brings a NIR absorption effect of Me-RBSs, and further gives rise to the NIR adsorption-dependent NIR responsive NO release profile. Intratumoral NIR-responsive release of NO effectively inhibits the growth and metastasis of the metastatic breast cancer. Aqueous insolubility of Me-RBSs ensures lower cytotoxicity and higher thermostability compared with traditional soluble RBSs. This work establishes a new class of NIR-sensitive NO donors, and may spark new inspiration for designing intelligent gas-releasing molecules. PMID- 28994572 TI - Water and Solute Transport Governed by Tunable Pore Size Distributions in Nanoporous Graphene Membranes. AB - Nanoporous graphene has the potential to advance membrane separations by offering high selectivity with minimal resistance to flow, but how mass transport depends on the structure of pores in this atomically thin membrane is poorly understood. Here, we investigate the relationship between tunable pore creation using ion bombardment and oxygen plasma etching, the resulting pore size distributions, and the consequent water and solute transport. Through tuning of the pore creation process, we demonstrate nanofiltration membranes that reject small molecules but offer high permeance to water or monovalent ions. Theoretical multiscale modeling of transport across the membranes reveals a disproportionate contribution of large pores to osmotic water flux and diffusive solute transport and captures the observed trends in transport measurements except for the smallest pores. This work provides insights into the effects of graphene pore size distribution and support layer on transport and presents a framework for designing atomically thin membranes. PMID- 28994573 TI - Preparation of a Sulfur-Functionalized Microporous Polymer Sponge and In Situ Growth of Silver Nanoparticles: A Compressible Monolithic Catalyst. AB - We report a compressible monolithic catalyst based on a microporous organic polymer (MOP) sponge. The monolithic MOP sponge was synthesized via Sonogashira Hagihara coupling reaction between 1,4-diiodotetrafluorobenzene and 1,3,5 triethynylbenzene in a cosolvent of toluene and TEA (2:1, v/v) without stirring. The MOP sponge had an intriguing microstructure, where tubular polymer fibers having a diameter of hundreds of nanometers were entangled. It showed hierarchical porosity with a Brunauer-Emmett-Teller (BET) surface area of 512 m2 g-1. The MOP sponge was functionalized with sulfur groups by the thiol-yne reaction. The functionalized MOP sponge exhibited a higher BET surface area than the MOP sponge by 13% due to the increase in the total pore and micropore volumes. A MOP sponge-Ag heterogeneous catalyst (S-MOPS-Ag) was prepared by in situ growth of silver nanoparticles inside the sulfur-functionalized MOP sponge by the reduction of Ag+ ions. The catalytic activity of S-MOPS-Ag was investigated for the reduction reaction of 4-nitrophenol in an aqueous condition. When S-MOPS-Ag was compressed and released during the reaction, the rate of the reaction was considerably increased. S-MOPS-Ag was easily removed from the reaction mixture owing to its monolithic character and was reused after washing and drying. PMID- 28994574 TI - Ultralow Friction Self-Lubricating Nanocomposites with Mesoporous Metal-Organic Frameworks as Smart Nanocontainers for Lubricants. AB - Smart nanocontainers with stimuli-responsive property can be used to fabricate a new kind of self-lubricating nanocomposite, while the practical potential of the metal-organic frameworks (MOFs) as nanocontainers for lubricants has not been realized. In this work, mesoporous Cu-BTC MOFs storing oleylamine nanocomposites were explored from synthesis and microstructure to self-lubricating characterization. The stress stimuli-responsiveness behavior of the Cu-BTC storing oleylamine (Cu-BTCO) for lubrication has been investigated by subjecting it to macroscopic ball-on-disc friction tests. The steady-state coefficients of friction (COFs) of the Cu-BTC nanocomposites without lubricants were ca. 0.5. In contrast, after oleylamine as the lubricant was incorporated into the Cu-BTC container in the nanocomposite, ultralow friction (COF, ca. 0.03) was achieved. It has been demonstrated that the improved lubricating performance was associated with the lubricating film which was in situ produced by the chemical reaction between the oleylamine released from the nanocontainer and the friction pairs. Therefore, the nanocomposite with smart Cu-BTC container holds the promise of realizing extraordinary self-lubricating properties under stress stimuli. PMID- 28994576 TI - Combined Computed Nanotomography and Nanoscopic X-ray Fluorescence Imaging of Cobalt Nanoparticles in Caenorhabditis elegans. AB - Synchrotron radiation phase-contrast computed nanotomography (nano-CT) and two- and three-dimensional (2D and 3D) nanoscopic X-ray fluorescence (nano-XRF) were used to investigate the internal distribution of engineered cobalt nanoparticles (Co NPs) in exposed individuals of the nematode Caenorhabditis elegans. Whole nematodes and selected tissues and organs were 3D-rendered: anatomical 3D renderings with 50 nm voxel size enabled the visualization of spherical nanoparticle aggregates with size up to 200 nm within intact C. elegans. A 20 * 37 nm2 high-brilliance beam was employed to obtain XRF elemental distribution maps of entire nematodes or anatomical details such as embryos, which could be compared with the CT data. These maps showed Co NPs to be predominantly present within the intestine and the epithelium, and they were not colocalized with Zn granules found in the lysosome-containing vesicles or Fe agglomerates in the intestine. Iterated XRF scanning of a specimen at 0 degrees and 90 degrees angles suggested that NP aggregates were translocated into tissues outside of the intestinal lumen. Virtual slicing by means of 2D XRF tomography, combined with holotomography, indicated presumable presence of individual NP aggregates inside the uterus and within embryos. PMID- 28994575 TI - Thrombin-Activatable Microbubbles as Potential Ultrasound Contrast Agents for the Detection of Acute Thrombosis. AB - Acute deep vein thrombosis (DVT) is the formation of a blood clot in the deep veins of the body that can lead to fatal pulmonary embolism. Acute DVT is difficult to distinguish from chronic DVT by ultrasound (US), the imaging modality of choice, and is therefore treated aggressively with anticoagulants, which can lead to internal bleeding. Here we demonstrate that conjugating perfluorobutane-filled (PFB-filled) microbubbles (MBs) with thrombin-sensitive activatable cell-penetrating peptides (ACPPs) could lead to the development of contrast agents that detect acute thrombosis with US imaging. Successful conjugation of ACPP to PFB-filled MBs was confirmed by fluorescence microscopy and flow cytometry. Fluorescein-labeled ACPP was used to evaluate the efficiency of thrombin-triggered cleavage by measuring the mean fluorescence intensity of ACPP-labeled MBs (ACPP-MBs) before and after incubation at 37 degrees C with thrombin. Lastly, control MBs and ACPP-MBs were infused through a tube containing a clot, and US contrast enhancement was measured with or without the presence of a thrombin inhibitor after washing the clot with saline. With thrombin activity, 91.7 +/- 14.2% of the signal was retained after ACPP-MB infusion and washing, whereas only 16.7 +/- 4% of the signal was retained when infusing ACPP-MBs in the presence of hirudin, a potent thrombin inhibitor. PMID- 28994577 TI - Improving Water-Treatment Performance of Zirconium Metal-Organic Framework Membranes by Postsynthetic Defect Healing. AB - Microporous metal-organic frameworks (MOFs) as building materials for molecular sieving membranes offer unique opportunities to tuning the pore size and chemical property. The recently reported polycrystalline Zr-MOF membranes have greatly expanded their applications from gas separation to water treatment. However, Zr MOFs are notoriously known for their intrinsic defects caused by ligand/cluster missing, which may greatly affect the molecular sieving property of Zr-MOF membranes. Herein, we present the mitigation of ligand-missing defects in polycrystalline UiO-66(Zr)-(OH)2 membranes by postsynthetic defect healing (PSDH), which can help in increasing the membranes' Na+ rejection rate by 74.9%. Intriguingly, the membranes also exhibit excellent hydrothermal stability in aqueous solutions (>600 h). Our study proves the feasibility of PSDH in improving the performance of polycrystalline Zr-MOF membranes for water-treatment applications. PMID- 28994578 TI - Tuning the Gold Nanoparticle Colorimetric Assay by Nanoparticle Size, Concentration, and Size Combinations for Oligonucleotide Detection. AB - Gold nanoparticle (GNP)-based aggregation assay is simple, fast, and employs a colorimetric detection method. Although previous studies have reported using GNP based colorimetric assay to detect biological and chemical targets, a mechanistic and quantitative understanding of the assay and effects of GNP parameters on the assay performance is lacking. In this work, we investigated this important aspect of the GNP aggregation assay including effects of GNP concentration and size on the assay performance to detect malarial DNA. Our findings lead us to propose three major competing factors that determine the final assay performance including the nanoparticle aggregation rate, plasmonic coupling strength, and background signal. First, increasing nanoparticle size reduces the Brownian motion and thus aggregation rate, but significantly increases plasmonic coupling strength. We found that larger GNP leads to stronger signal and improved limit of detection (LOD), suggesting a dominating effect of plasmonic coupling strength. Second, higher nanoparticle concentration increases the probability of nanoparticle interactions and thus aggregation rate, but also increases the background extinction signal. We observed that higher GNP concentration leads to stronger signal at high target concentrations due to higher aggregation rate. However, the fact the optimal LOD was found at intermediate GNP concentrations suggests a balance of two competing mechanisms between aggregation rate and signal/background ratio. In summary, our work provides new guidelines to design GNP aggregation-based POC devices to meet the signal and sensitivity needs for infectious disease diagnosis and other applications. PMID- 28994579 TI - Dual Amplification Fluorescence Assay for Alpha Fetal Protein Utilizing Immunohybridization Chain Reaction and Metal-Enhanced Fluorescence of Carbon Nanodots. AB - As an emerging fascinating fluorescent nanomaterial, carbon nanodots (CDs) have attracted much attention owing of their unique properties such as small size, antiphotobleaching, and biocompatibility. However, its use in biomedical analysis is limited because of its low quantum yield. Herein, we constructed a dual amplification fluorescence sensor by incorporating immunohybridization chain reaction (immuno-HCR) and metal-enhanced fluorescence (MEF) of CDs for the detection of alpha fetal protein (AFP). The immunoplasmonic slide and detection antibodies-conjugated oligonucleotide initiator are served to capture and probe AFP molecules, respectively. Then, CD-tagged hairpin nucleic acids were introduced to trigger the HCR, in which the hairpin nucleic acid and oligonucleotide initiator are complementary. The interaction between CDs and the gold nanoisland film greatly improves the radiative decay rate, increases the quantum yield, and enhances the fluorescence emission of the CDs. Furthermore, the HCR provides secondary amplification of fluorescence intensity. Therefore, the MEF-capable immunohybridization reactions provide obvious advantages and result in exceptional sensitivity. In addition, the sandwich immunoassay method offers high specificity. The results show a wide linearity between the fluorescence intensity and AFP concentration over 5 orders of magnitude (0.0005-5 ng/mL), and the detection limit reaches as low as 94.3 fg/mL. This method offers advantages of high sensitivity and reliability, wide detection range, and versatile plasmonic chips, thus presenting an alternative for the technologies in biomedical analysis and clinical applications. PMID- 28994580 TI - Surface Hydrogenation of Boron-Doped Diamond Electrodes by Cathodic Reduction. AB - Boron-doped diamond (BDD) has attracted much attention as a promising electrode material especially for electrochemical sensing systems, because it has excellent properties such as a wide potential window and low background current. It is known that the electrochemical properties of BDD electrodes are very sensitive to the surface termination such as to whether it is hydrogen- or oxygen-terminated. Pretreating BDD electrodes by cathodic reduction (CR) to hydrogenate the surface has been widely used to achieve high sensitivity. However, little is known about the effects of the CR treatment conditions on surface hydrogenation. In this Article, we report on a systematic study of CR treatments that can achieve effective surface hydrogenation. As a result, we found that the surface hydrogenation could be improved by applying a more negative potential in a lower pH solution. This is because hydrogen atoms generated from protons in the CR treatment contribute to the surface hydrogenation. After CR treatments, BDD surface could be hydrogenated not completely but sufficiently to achieve high sensitivity for electrochemical sensing. In addition, we confirmed that hydrogenation with high repeatability could be achieved. PMID- 28994581 TI - Sulfur-Doped Graphene-Based Immunological Biosensing Platform for Multianalysis of Cancer Biomarkers. AB - The accurate tumor marker detection at an early stage can prevent people from getting cancer to a great extent. Herein, a novel tri-antibody dual-channel biosensing strategy is applied in multianalysis of carcino-embryonic antigen (CEA) and nuclear matrix protein 22 (NMP22). In this immunosensor fabrication process, graphene oxide/polyaniline nanostructures are used as matrix and mesoporous NKF-5-3 is used as labels. Two kinds of antigens can be obtained from the signals of neutral red and toluidine blue, respectively, which are modified on the labels. In this tri-antibody dual-channel biosensing platform, sulfur doped graphene sheet is synthesized by click chemistry as the framework structure. Majority of the incubations are conducted in individual steps, which ensure the surface incubation more tightly. The detection limit of NMP22 and CEA are 25 and 30 fg/mL, respectively. The low detection limit and excellent stability can ascribe to the tri-antibody dual-channel strategy, which makes the sensor platform from surface to the space. The clinical urine sample analysis achieves a good performance. The urine-based test can avoid the secondary injury on hemophilia or ischemic patients, displaying a potential application in clinical diagnosis. PMID- 28994582 TI - Internal Light Source-Driven Photoelectrochemical 3D-rGO/Cellulose Device Based on Cascade DNA Amplification Strategy Integrating Target Analog Chain and DNA Mimic Enzyme. AB - In this work, a chemiluminescence-driven collapsible greeting card-like photoelectrochemical lab-on-paper device (GPECD) with hollow channel was demonstrated, in which target-triggering cascade DNA amplification strategy was ingeniously introduced. The GPECD had the functions of reagents storage and signal collection, and the change of configuration could control fluidic path, reaction time and alterations in electrical connectivity. In addition, three dimentional reduced graphene oxide affixed Au flower was in situ grown on paper cellulose fiber for achieving excellent conductivity and biocompatibility. The cascade DNA amplification strategy referred to the cyclic formation of target analog chain and its trigger action to hybridization chain reaction (HCR), leading to the formation of numerous hemin/G-quadruplex DNA mimic enzyme with the presence of hemin. Subjected to the catalysis of hemin/G-quadruplex, the strong chemiluminiscence of luminol-H2O2 system was obtained, which then was used as internal light source to excite photoactive materials realizing the simplification of instrument. In this analyzing process, thrombin served as proof of-concept, and the concentration of target was converted into the DNA signal output by the specific recognition of aptamer-protein and target analog chain recycling. The target analog chain was produced in quantity with the presence of target, which further triggered abundant HCR and introduced hemin/G-quadruplex into the system. The photocurrent signal was obtained after the nitrogen-doped carbon dots sensitized ZnO was stimulated by chemiluminescence. The proposed GPECD exhibited excellent specificity and sensitivity toward thrombin with a detection limit of 16.7 fM. This judiciously engineered GPECD paved a luciferous way for detecting other protein with trace amounts in bioanalysis and clinical biomedicine. PMID- 28994583 TI - A Vision for Vaccines: Combating the Opioid Epidemic. PMID- 28994584 TI - Highly Efficient Red and White Organic Light-Emitting Diodes with External Quantum Efficiency beyond 20% by Employing Pyridylimidazole-Based Metallophosphors. AB - Two highly efficient red neutral iridium(III) complexes, Ir1 and Ir2, were rationally designed and synthesized by selecting two pyridylimidazole derivatives as the ancillary ligands. Both Ir1 and Ir2 show nearly the same photoluminescence emission with the maximum peak at 595 nm (shoulder band at about 638 nm) and achieve high solution quantum yields of up to 0.47 for Ir1 and 0.57 for Ir2. Employing Ir1 and Ir2 as emitters, the fabricated red organic light-emitting diodes (OLEDs) show outstanding performance with the maximum external quantum efficiency (EQE), current efficiency (CE), and power efficiency (PE) of 20.98%, 33.04 cd/A, and 33.08 lm/W for the Ir1-based device and 22.15%, 36.89 cd/A, and 35.85 lm/W for the Ir2-based device, respectively. Furthermore, using Ir2 as red emitter, a trichromatic hybrid white OLED, showing good warm white emission with low correlated color temperature of <2200 K under the voltage of 4-6 V, was fabricated successfully. The white device also realizes excellent device efficiencies with the maximum EQE, CE, and PE reaching 22.74%, 44.77 cd/A, and 46.89 lm/W, respectively. Such high electroluminescence performance for red and white OLEDs indicates that Ir1 and Ir2 as efficient red phosphors have great potential for future OLED displays and lightings applications. PMID- 28994585 TI - Amplifying (Im)perfection: The Impact of Crystallinity in Discrete and Disperse Block Co-oligomers. AB - Crystallinity is seldomly utilized as part of the microphase segregation process in ultralow-molecular-weight block copolymers. Here, we show the preparation of two types of discrete, semicrystalline block co-oligomers, comprising an amorphous oligodimethylsiloxane block and a crystalline oligo-l-lactic acid or oligomethylene block. The self-assembly of these discrete materials results in lamellar structures with unforeseen uniformity in the domain spacing. A systematic introduction of dispersity reveals the extreme sensitivity of the microphase segregation process toward chain length dispersity in the crystalline block. PMID- 28994587 TI - Concerted Mechanisms of Excited-State Proton Intramolecular Transfer for Bis-2,4 (2-benzoxazolyl)-hydroquinone and Its Derivatives. AB - The concerted mechanisms of excited state intramolecular proton transfer (ESIPT) of bis-2,4-(2-benzoxazolyl)-hydroquinone (BBHQ') and its derivatives (BBHQ'- and DHBO') have been investigated using the density functional theory (DFT) and the time-dependent density functional theory (TDDFT). The calculated absorption and emission spectra of BBHQ' and its derivatives are in good agreement with the experimental results. The calculated bond lengths, bond angles, and IR vibrational spectra linked with hydrogen bond of molecular BBHQ' in the S0 and S1 states demonstrate that the hydrogen bond is strengthened in the S1 state. Compared to BBHQ', BBHQ'- has a weak change of hydrogen bond between the S1 and S0 states. The calculation results show that there are three stable structures of BBHQ' in the S1 state. We find that the structure corresponding to the 481 nm fluorescence spectrum corresponds to BBHQ'-A rather than BBHQ'--K (Tetrahedron Lett., 2016, 57, 3518). The calculated frontier molecular orbitals (MOs) indicate the nature of the charge distribution and the trend of proton transfer of BBHQ' A. The constructed potential energy surfaces of BBHQ' and DBHO' further elucidate the proposed mechanism that one-proton or two-proton transfer can happen (stepwise or synchronous) in the S1 states. The proposed ESIPT mechanism can provide a good explanation of the phenomenon of fluorescence quenching of BBHQ' and its derivatives. Finally, the weak interaction types are discriminated through the reduced density gradient (RDG) analyses of BBHQ' and BBHQ'-. PMID- 28994586 TI - Colossal Volume Contraction in Strong Polar Perovskites of Pb(Ti,V)O3. AB - The unique physical property of negative thermal expansion (NTE) is not only interesting for scientific research but also important for practical applications. Chemical modification generally tends to weaken NTE. It remains a challenge to obtain enhanced NTE from currently available materials. Herein, we successfully achieve enhanced NTE in Pb(Ti1-xVx)O3 by improving its ferroelectricity. With the chemical substitution of vanadium, lattice tetragonality (c/a) is highly promoted, which is attributed to strong spontaneous polarization, evidenced by the enhanced covalent interaction in the V/Ti-O and Pb O2 bonds from first-principles calculations. As a consequence, Pb(Ti0.9V0.1)O3 exhibits a nonlinear and much stronger NTE over a wide temperature range with a volumetric coefficient of thermal expansion alphaV = -3.76 * 10-5/ degrees C (25 550 degrees C). Interestingly, an intrinsic giant volume contraction (~3.7%) was obtained at the composition of Pb(Ti0.7V0.3)O3 during the ferroelectric-to paraelectric phase transition, which represents the highest value ever reported. Such volume contraction is well correlated to the effect of spontaneous volume ferroelectrostriction. The present study extends the scope of the NTE family and provides an effective approach to explore new materials with large NTE, such as through adjusting the NTE-related ferroelectric property in the family of ferroelectrics. PMID- 28994588 TI - Regulation of the Oligomeric Status of CCR3 with Binding Ligands Revealed by Single-Molecule Fluorescence Imaging. AB - The relationship between the oligomeric status and functions of chemokine receptor CCR3 is still controversial. We use total internal reflection fluorescence microscopy at the single-molecule level to visualize the oligomeric status of CCR3 and its regulation of the membrane of stably transfected T-REx-293 cells. We find that the population of the dimers and oligomers of CCR3 can be modulated by the binding of ligands. Natural agonists can induce an increase in the level of dimers and oligomers at high concentrations, whereas antagonists do not have a significant influence on the oligomeric status. Moreover, monomeric CCR3 exhibits a stronger chemotactic response in the migration assay of stably transfected CCR3 cells. Together, these data support the notion that CCR3 exists as a mixture of monomers and dimers under nearly physiological conditions and the monomeric CCR3 receptor is the minimal functional unit in cellular signaling transduction. To the best of our knowledge, these results constitute the first report of the oligomeric status of CCR3 and its regulation. PMID- 28994589 TI - What on Earth Have We Been Burning? Deciphering Sedimentary Records of Pyrogenic Carbon. AB - Humans have interacted with fire for thousands of years, yet the utilization of fossil fuels marked the beginning of a new era. Ubiquitous in the environment, pyrogenic carbon (PyC) arises from incomplete combustion of biomass and fossil fuels, forming a continuum of condensed aromatic structures. Here, we develop and evaluate 14C records for two complementary PyC molecular markers, benzene polycarboxylic acids (BPCAs) and polycyclic aromatic hydrocarbons (PAHs), preserved in aquatic sediments from a suburban and a remote catchment in the United States (U.S.) from the mid-1700s to 1998. Results show that the majority of PyC stems from local sources and is transferred to aquatic sedimentary archives on subdecadal to millennial time scales. Whereas a small portion stems from near-contemporaneous production and sedimentation, the majority of PyC (~90%) experiences delayed transmission due to "preaging" on millennial time scales in catchment soils prior to its ultimate deposition. BPCAs (soot) and PAHs (precursors of soot) trace fossil fuel-derived PyC. Both markers parallel historical records of the consumption of fossil fuels in the U.S., yet never account for more than 19% total PyC. This study demonstrates that isotopic characterization of multiple tracers is necessary to constrain histories and inventories of PyC and that sequestration of PyC can markedly lag its production. PMID- 28994590 TI - Oxygen-Centered Radicals Formed in the Reaction Mixtures Containing Chloroiron Tetraphenylporphyrin, Iodosylbenzene, and Ethanol. AB - Heme and nonheme high-valent FeIV?O can mediate reactions of olefin epoxidation, alkane hydroxylation, aromatic hydroxylation, S-oxidation, P-oxidation, N dealkylation, alkylaromatic oxidation, and alcohol oxidation. Bromocycloheptane forms as a product in the reaction of high-valent FeIV?O with cycloheptane, suggesting that a cycloheptyl radical reacts with CCl3Br. However, the cycloheptyl radical has not yet been directly detected. To directly detect the radical intermediate in the reaction of the high-valent FeIV?O, we analyzed reaction mixtures containing chloroiron tetraphenylporphyrin, iodosylbenzene, ethanol, and alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (4-POBN) in 1,2 dichloroethane by an electron spin resonance (ESR) spin-trapping method. As a spin-trapping reagent, we used 4-POBN. Prominent ESR signals were observed in the reaction mixtures. To determine the structure of the radical, the reaction was performed using ethanol-1-13C (or ethanol-2-13C) instead of ethanol. ESR spectra with no additional hyperfine splitting were observed, indicating that the radical formed in complete reaction mixtures of the porphyrin pi-cation-radical species (TPP)*+FeIV?O (TPP = 5,10,15,20-tetraphenyl-21H,23H-porphine) with ethanol has an unpaired electron at neither the alpha-carbon nor the beta-carbon. When the reaction mixture containing ethanol-d6 instead of ethanol was analyzed using high performance liquid chromatography-ESR-mass spectrometry, the ions m/z 240 (4 POBN/*OCH2CH3) shifted to m/z 245 (4-POBN/*OCD2CD3). Thus, the radical formed in the complete reaction mixture of (TPP)*+FeIV?O with ethanol has an unpaired electron at the oxygen atom in ethanol. We detected and identified the ethanol derived oxygen-centered radicals in the reaction of (TPP)*+FeIV?O with ethanol for the first time in this study. PMID- 28994591 TI - Geometrical Optimization Approach to Isomerization: Models and Limitations. AB - We study laser-driven isomerization reactions through an excited electronic state using the recently developed Geometrical Optimization procedure. Our goal is to analyze whether an initial wave packet in the ground state, with optimized amplitudes and phases, can be used to enhance the yield of the reaction at faster rates, driven by a single picosecond pulse or a pair of femtosecond pulses resonant with the electronic transition. We show that the symmetry of the system imposes limitations in the optimization procedure, such that the method rediscovers the pump-dump mechanism. PMID- 28994592 TI - Zero-Valent Iron Enhances Biocathodic Carbon Dioxide Reduction to Methane. AB - Methanogenic bioelectrochemical systems (BESs), which convert carbon dioxide (CO2) directly to methane (CH4), promise to be an innovative technology for anaerobic digester biogas upgrading. Zero-valent iron (ZVI), which has previously been used to improve CH4 production in anaerobic digesters, has not been explored in methanogenic biocathodes. Thus, the objective of this study was to assess the effect of biocathode ZVI on BES performance at 1 and 2 g/L initial ZVI concentrations and at various cathode potentials (-0.65 to -0.80 V versus SHE). The total CH4 produced during a 7-day feeding cycle with 1 and 2 g/L initial ZVI was 2.8- and 2.9-fold higher, respectively, than the mean CH4 production in the four prior cycles without ZVI addition. Furthermore, CH4 production by the ZVI amended biocathodes remained elevated throughout three subsequent feeding cycles, despite catholyte replacement and no new ZVI addition. The fourth cycle following a single ZVI addition of 1 g/L and 2 g/L yielded 123% and 231% more total CH4 than in the non-ZVI cycles, respectively. The higher CH4 production could not be fully explained by complete anaerobic oxidation of the ZVI and utilization of produced H2 by hydrogenotrophic methanogens. Microbial community analysis showed that the same phylotype, most closely related to Methanobrevibacter arboriphilus, dominated the archaeal community in the ZVI-free and ZVI-amended biocathodes. However, the bacterial community experienced substantial changes following ZVI exposure, with more Proteobacteria and fewer Bacteroidetes in the ZVI-amended biocathode. Furthermore, it is likely that a redox-active precipitate formed in the ZVI-amended biocathode, which sorbed to the electrode and/or biofilm, acted as a redox mediator, and enhanced electron transfer and CH4 production. Thus, ZVI may be used to increase biocathode CH4 production, assist in the start-up of an electromethanogenic biocathode, and/or maintain microbial activity during voltage interruptions. PMID- 28994593 TI - A One-Step Rapid Assembly of Thin Film Coating Using Green Coordination Complexes for Enhanced Removal of Trace Organic Contaminants by Membranes. AB - We report a fast, simple, and green coating method using the coordination complex of tannic acid (TA) and ferric ion (Fe3+) to enhance the removal of trace organic contaminants (TrOCs) by polyamide membranes. The entire coating process can be completed in less than 2 min; quartz crystal microbalance characterization revealed that a TA-Fe thin film formed in merely 10-20 s. Coating this TA-Fe thin film on a commercial nanofiltration membrane (NF270) reduced its effective pore size from 0.44 to 0.40 nm. The TA-Fe-coated NF270 showed significantly increased rejection of both NaCl and trace organic contaminants. In comparison with the more-time-consuming polydopamine coating (e.g., 0.5 h), the TA-Fe coating presented greater resistance to TrOC permeation (i.e., lower permeability of TrOCs). The advantages of the fast coating process, greatly improved rejection performance, and use of green accessible materials make TA-Fe a highly promising coating material for large-scale applications. PMID- 28994594 TI - Benzoyl Peroxide Detection in Real Samples and Zebrafish Imaging by a Designed Near-Infrared Fluorescent Probe. AB - A novel near-infrared fluorescence off-on probe, (E)-3,3-dimethyl-1-propyl-2-(2 (6-(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyloxy)-2,3-dihydro-1H xanthen-4-yl)vinyl)-3H-indolium (1), is developed and applied to benzoyl peroxide (BPO) detection in real samples and fluorescence imaging in living cells and zebrafish. When arylboronate as the recognition unit is connected to a stable hemicyanine skeleton, the probe is readily prepared, which exhibits superior analytical performance, such as near-infrared fluorescence emission over 700 nm and high sensitivity with a low detection limit of 47 nM. Upon reaction with BPO, phenylboronic acid pinacol ester is oxidized, followed by hydrolysis and 1,4 elimination of o-quinone methide to release fluorophore. In addtion, the probe displays high selectivity toward BPO over other common substances, which makes it of great potential use in quantitative and simple detection of BPO in wheat flour and antimicrobial agent. More importantly, the probe has been successfully demonstrated for monitoring BPO in living HeLa cells and zebrafish. The probe with superior properties could be of great potential use in other biosystems and in vivo studies. PMID- 28994595 TI - Pertechnetate-Induced Addition of Sulfide in Small Olefinic Acids: Formation of [TcO(dimercaptosuccinate)2]5- and [TcO(mercaptosuccinate)2]3- Analogues. AB - Technetium-99 (99Tc) is important to the nuclear fuel cycle as a long-lived radionuclide produced in ~6% fission yield from 235U or 239Pu. In its most common chemical form, namely, pertechnetate (99TcO4-), it is environmentally mobile. In situ hydrogen sulfide reduction of pertechnetate has been proposed as a potential method to immobilize environmental 99TcO4- that has entered the environment. Reactions of 99TcO4- with sulfide in solution result in the precipitation of Tc2S7 except when olefinic acids, specifically fumaric or maleic acid, are present; a water-soluble 99Tc species forms. NMR (1H, 13C, and 2D methods) and X ray absorption spectroscopy [XAS; near-edge (XANES) and extended fine structure (EXAFS)] studies indicate that sulfide adds across the olefinic bond to generate mercaptosuccinic acid (H3MSA) and/or dimercaptosuccinic acid (H4DMSA), which then chelate(s) the 99Tc to form [99TcO(MSA)2]3-, [99TcO(DMSA)2]5-, or potentially [99TcO(MSA)(DMSA)]4-. 2D NMR methods allowed identification of the products by comparison to 99Tc and nonradioactive rhenium standards. The rhenium standards allowed further identification by electrospray ionization mass spectrometry. 99TcO4- is essential to the reaction because no sulfide addition occurs in its absence, as determined by NMR. Computational studies were performed to investigate the structures and stabilities of the potential products. Because olefinic acid is a component of the naturally occurring humic and fulvic acids found in soils and groundwater, the viability of in situ hydrogen sulfide reduction of environmental 99TcO4- as an immobilization method is evaluated. PMID- 28994596 TI - 16S rRNA Gene Amplicon Sequencing Reveals Significant Changes in Microbial Compositions during Cyanobacteria-Laden Drinking Water Sludge Storage. AB - This is the first study to systematically investigate the microbial community structure in cyanobacteria-laden drinking water sludge generated by different types of coagulants (including AlCl3, FeCl3, and polymeric aluminum ferric chloride (PAFC)) using Illumina 16S rRNA gene MiSeq sequencing. Results show that Cyanobacteria, Proteobacteria, Firmicutes, Bacteroidetes, Verrucomicrobia, and Planctomycetes were the most dominant phyla in sludge, and because of the toxicity of high Al and Fe level in AlCl3 and FeCl3 sludges, respectively, the PAFC sludge exhibited greater microbial richness than that in AlCl3 and FeCl3 sludges. Due to lack of light and oxygen in sludge, relative abundance of the dominant genera Microcystis, Rhodobacter, Phenylobacterium, and Hydrogenophaga clearly decreased, especially after 4 days storage, and the amounts of extracellular microcystin and organic matter rose. As a result, the relative abundance of microcystin and organic degradation bacteria increased significantly, including pathogens such as Bacillus cereus, in particular after 4 days storage. Hence, sludge should be disposed of within 4 days to prevent massive growth of pathogens. In addition, because the increase of extracellular microcystins, organic matter, and pathogens in AlCl3 sludge was higher than that in FeCl3 and PAFC sludges, FeCl3 and PAFC may be ideal coagulants in drinking water treatment plants. PMID- 28994597 TI - Methodology for Monobactam Diversification: Syntheses and Studies of 4-Thiomethyl Substituted beta-Lactams with Activity against Gram-Negative Bacteria, Including Carbapenemase Producing Acinetobacter baumannii. AB - Bromine induced lactamization of vinyl acetohydroxamates facilitated syntheses of monocyclic beta-lactams suitable for incorporation of a thiomethyl and extended functionality at the C(4) position. Elaboration of the resulting substituted N hydroxy-2-azetidinones allowed incorporation of functionalized alpha-amino substituents appropriate for enhancement of antibiotic activity. Evaluation of antibacterial activity against a panel of Gram-positive and Gram-negative bacteria revealed structure-activity relationships (SAR) and identification of potent new monobactam antibiotics. The corresponding bis-catechol conjugate, 42, has excellent activity against Gram-negative bacteria including carbapenemase and carbacephalosporinase producing strains of Acinetobacter baumannii, which have been listed by the WHO as being of critical concern worldwide. PMID- 28994598 TI - Hysteresis and Photoinstability Caused by Mobile Ions in Colloidal Quantum Dot Photovoltaics. AB - Organic-inorganic hybrid photovoltaics (PVs) have recently attracted considerable attention as their PV performance has rapidly improved. Abnormal current-voltage (I-V) characteristics or I-V hysteresis, however, were occasionally observed in such systems that hampered the development of the PV technology. Here we study the hysteresis of organic-inorganic hybrid colloidal quantum dot (CQD) PVs by analyzing I-V characteristics upon systematic modulation of organic components of CQDs. We demonstrate that an external bias stress to CQD films transiently prompts redistribution of mobile ions, particularly protons of surface ligands, thus leading to the formation of a transient space-charge region in the CQD films. The variable space-charge region causes I-V hysteresis and photoinstability of CQD PVs, which is closely correlated with the transient behavior of mobile ions. Our findings here could provide significant implications to the understanding of the influence of mobile ions on I-V hysteresis in other organic-inorganic hybrid PVs such as perovskites. PMID- 28994599 TI - Metabolomics and Lipidomics Study of Mouse Models of Type 1 Diabetes Highlights Divergent Metabolism in Purine and Tryptophan Metabolism Prior to Disease Onset. AB - With the increase in incidence of type 1 diabetes (T1DM), there is an urgent need to understand the early molecular and metabolic alterations that accompany the autoimmune disease. This is not least because in murine models early intervention can prevent the development of disease. We have applied a liquid chromatography (LC-) and gas chromatography (GC-) mass spectrometry (MS) metabolomics and lipidomics analysis of blood plasma and pancreas tissue to follow the progression of disease in three models related to autoimmune diabetes: the nonobese diabetic (NOD) mouse, susceptible to the development of autoimmune diabetes, and the NOD-E (transgenic NOD mice that express the I-E heterodimer of the major histocompatibility complex II) and NOD-severe combined immunodeficiency (SCID) mouse strains, two models protected from the development of diabetes. All three analyses highlighted the metabolic differences between the NOD-SCID mouse and the other two strains, regardless of diabetic status indicating that NOD-SCID mice are poor controls for metabolic changes in NOD mice. By comparing NOD and NOD-E mice, we show the development of T1DM in NOD mice is associated with changes in lipid, purine, and tryptophan metabolism, including an increase in kynurenic acid and a decrease in lysophospholipids, metabolites previously associated with inflammation. PMID- 28994600 TI - Cleavable Multifunctional Targeting Mixed Micelles with Sequential pH-Triggered TAT Peptide Activation for Improved Antihepatocellular Carcinoma Efficacy. AB - Although tumor-targeting nanovehicles for hepatocellular carcinoma (HCC) chemotherapy have attracted great research and clinic interest, the poor cancer penetration, inefficient cellular uptake, and slow intracellular drug release greatly compromise their therapeutic outcomes. In this work, a multifunctional mixed micellar system, consisting of glycyrrhetinic acid (GA) for specific liver targeting, trans-activator of transcription (TAT) peptide for potent cell penetration, and pH-sensitive poly(beta-amino ester) polymers for acidic triggered drug release, was developed to provide HCC-targeting delivery and pH triggered release of doxorubicin (DOX). These micelles were hypothesized to efficaciously accumulate in HCC site by the guide of GA ligands, enter into cancer cells facilitated by the activated TAT peptide on the micellar surface, and finally rapidly release DOX in cytoplasm. To demonstrate this design, DOX was initially loaded in micelles modified with both GA and TAT (DOX/GA@TAT-M) with high drug loading efficiency and pH-sensitive drug release profiles. The HCC targeting cellular uptake and synergetic anticancer efficacy were tested, indicating DOX/GA@TAT-M could be specifically and effectively internalized into HCC cells by the effect of GA targeting and TAT penetrating with enhanced cytotoxicity. In addition, the prolonged circulation time and enhanced accumulation in tumor facilitated its potent tumor growth inhibition activity in vivo. These results demonstrated that the cleavable multifunctional mixed micelles with tumor targeting, controlled TAT peptide activation, and sequential pH-sensitive drug release could be an efficient strategy for HCC treatment. PMID- 28994601 TI - Infrared-Enhanced Fluorescence-Gain Spectroscopy: Conformation-Specific Excited State Infrared Spectra of Alkylbenzenes. AB - An ultraviolet-infrared (UV-IR) double-resonance method for recording conformation-specific excited-state infrared spectra is described. The method takes advantage of an increase in fluorescence signal in phenylalkanes produced by infrared excitation of the S1 origin levels of different conformational isomers. The shorter lifetimes of these IR-excited molecules, combined with their red-shifted emission, provides a way to discriminate the fluorescence due to the infrared-excited molecules from the S1 origin fluorescence, resulting in spectra with high signal-to-noise ratios. Spectra for a series of phenylalkanes and a capped phenylalanine derivative (Ac-Phe-NHMe) demonstrate the potential of the method. The excited-state spectrum in the alkyl CH stretch region of ethylbenzene is well-fit by an anharmonic model developed for the ground electronic state, which explicitly takes into account stretch-bend Fermi resonance. PMID- 28994602 TI - Hydroboration Catalyzed by 1,2,4,3-Triazaphospholenes. AB - The synthesis and study of the catalytic activity of 1,2,4,3-triazaphospholenes (TAPs) is reported. TAPs represent a more modular scaffold than previously reported diazaphospholenes. TAP halides were shown to catalyze the 1,2 hydroboration of 19 imines, and three alpha,beta unsaturated aldehydes with pinacolborane, including examples that did not undergo hydroboration by previously reported diazaphospholene systems. DFT calculations support a mechanism where a triazaphospholene cation interacts with the substrate, a mechanism distinct from diazaphospholene catalyzed hydroborations. PMID- 28994603 TI - Suvorexant: scientifically interesting, utility uncertain. AB - OBJECTIVE: Suvorexant, a new hypnotic, is indicated for the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance, and is used long-term. This paper will briefly review suvorexant. RESULTS: Orexin is a hypothalamic peptide which promotes wakefulness. By blocking orexin receptors, suvorexant induces sleep. Peaking 2 h after ingestion, it has a half-life of 12 h and is hepatically metabolized mainly by CYP3A. Kinetics are not affected by age but concentrations are higher in females and obese patients. There may be interactions with benzodiazepines, antidepressants and antipsychotics. Suvorexant is available in 15 mg and 20 mg doses at which benefits are moderate: after three months' treatment users fell asleep 6 min faster and slept 16 min longer than those on placebo. Studies with 40 mg showed greater benefits but more side effects: next day somnolence, fatigue, xerostomia and peripheral oedema. Hallucinations, sleep paralysis and somnambulism occur rarely. Tolerance, withdrawal and rebound do not generally occur at recommended doses. CONCLUSION: Suvorexant has not been trialled against other hypnotics, is expensive and its utility for insomnia in patients with psychiatric disorders is unknown. Currently, use of suvorexant could be considered where more established treatments are inappropriate. PMID- 28994604 TI - National awareness campaign to prevent medication-overuse headache in Denmark. AB - Background Medication-overuse headache is prevalent, but in principle preventable. Objective To describe the Danish national awareness campaign for medication-overuse headache. Methods The Danish Headache Center, the Association of Danish Pharmacies, and headache patient organizations implemented a four-month medication-overuse headache awareness campaign in 2016. Target groups were the general public, general practitioners, and pharmacists. Key messages were: Overuse of pain-medication can worsen headaches; pain-medication should be used rationally; and medication-overuse headache is treatable. A range of communication technologies was used. A survey on the public's awareness of medication-overuse headache was conducted. Results The Danish adult population is 4.2 million. Online videos were viewed 297,000 times in three weeks. All 400 pharmacies received campaign materials. Over 28,000 leaflets were distributed. Two radio interviews were conducted. A television broadcast about headache reached an audience of 520,000. Forty articles were published in print media. Information was accessible at 32 reputable websites and five online news agencies. Three scientific papers were published. Information was available at an annual conference of general practitioners, including a headache lecture. The survey showed an increase in percentage of the public who knew about medication overuse headache (from 31% to 38%). Conclusion A concerted campaign to prevent medication-overuse headache can be implemented through involvement of key stakeholders. PMID- 28994605 TI - Explicit diagnostic criteria for transient ischemic attacks to differentiate it from migraine with aura. AB - Background The diagnosis of transient ischemic attacks is fraught with problems. The inter-observer agreement has repeatedly been shown to be low even in a neurological setting, and the specificity of the diagnosis is modest to low, reflected in a poor separation of transient ischemic attacks and mimics, particularly migraine with aura with its varied symptomatology. In other disease areas, explicit diagnostic criteria have improved sensitivity and specificity of diagnoses. We therefore present novel explicit diagnostic criteria for transient ischemic attacks tested for sensitivity and for specificity against migraine with aura. Methods The proposed criteria were developed using the format of the international headache classification. We drew upon the existing literature about clinical characteristics and diagnosis of migraine with aura and transient ischemic attacks. We tested the criteria for sensitivity in a prospectively collected material of 120 patients with transient ischemic attacks diagnosed before we developed the criteria using extensive semi-structured interview forms in the acute phase after admission. Eligible patients had focal brain or retinal ischemia with resolution of symptoms within 24 hours without presence of new infarction on magnetic resonance imaging with diffusion weighted imaging (n = 112) or computed tomography (n = 8). These criteria were also tested for specificity against a Danish (n = 1390) and a Russian (n = 152) material of patients with migraine with aura diagnosed according to the International Classification of Headache Disorders edition 3 (beta). Results The sensitivity of the proposed criteria was 99% in patients with transient ischemic attacks. The specificity was 95% in the Danish material of patients with migraine with aura and 96% in the Russian material. Conclusions Proposed explicit diagnostic criteria for transient ischemic attacks showed both high specificity and sensitivity. They are likely to improve the emergency room diagnosis of transient ischemic attacks. Further testing in unselected materials referred to transient ischemic attacks clinics was beyond the scope of the present study but is recommended for future study. PMID- 28994611 TI - Modeling the survival of Salmonella Enteritidis and Salmonella Typhimurium during the fermentation of yogurt. AB - The objective of this study was to evaluate the behavior of Salmonella Enteritidis and Salmonella Typhimurium, the two most important serovars of salmonellosis , during the fermentation of yogurt. The microorganisms were enumerated in milk throughout the fermentation process at three initial inoculum levels (3, 5 and 7 log CFU/mL). DMFit software was used in the fitting procedure of the data (IFR, Norwich, UK, Version 3.5). The data provided sigmoidal curves that were successfully displayed with the Baranyi model. The results showed that the initial inoculum level did not affect the growth for both pathogens; thus, the umax values (maximum specific growth rate) did not significantly differ across all the contamination levels, ranging from 0.26 to 0.38 for S. Enteritidis and from 0.50 to 0.56 log CFU/g/h for S. Typhimurium ( P > 0.05). However, the umax values significantly differed between the two serovars ( P < 0.05). The lambda values (lag time) did not have a clear trend in either of the pathogens. The present study showed that Salmonella can survive the fermentation process of milk even at a low contamination level. In addition, the models presented in this study can be used in quantitative risk assessment studies to estimate the threat to consumers. PMID- 28994612 TI - Metal Concentrations in Samples of Frozen Cephalopods (Cuttlefish, Octopus, Squid, and Shortfin Squid): An Evaluation of Dietary Intake. AB - Cephalopods are an important source of nutrients and some of the most widely consumed marine foods. However, because of contamination of the oceans and the bioaccumulative nature of toxic metals, these foods may pose a health risk. For this reason, the concentrations of some trace elements (chromium [Cr], lithium, strontium [Sr], copper [Cu], and nickel) and toxic metals (aluminum [Al], cadmium, and lead) were determined in 65 frozen samples of cuttlefish, octopus, common squid, and shortfin squid by inductively coupled plasma optical emission spectrometry to evaluate dietary intake and toxic risk. Sr was the major trace element (3.03 mg/kg) in cuttlefish; however, Cu (1.57 mg/kg) was found in the highest concentration in common squid. Among the toxic metals, Al had the highest concentration (3.09 mg/kg) in common squid. Al can pose an important health risk to individuals with kidney problems and to children because these groups are most vulnerable to the toxic effects. Significant differences among the four cephalopod types were found in the concentrations of most of the metals examined. Taking into account the average consumption of cephalopods, the contribution of toxic metals does not pose a risk to the health of adults. PMID- 28994613 TI - Gyrase A Mutations in Campylobacter Associated with Decreased Susceptibility to Different Fluoroquinolones. AB - Campylobacter is a leading cause of foodborne diarrheal illness worldwide, and the emergence of antimicrobial-resistant strains is a major global public health concern. The goal of this study was to compare the activity of different fluoroquinolone antibiotics against ciprofloxacin-resistant Campylobacter jejuni and Campylobacter coli. Isolates from retail meats collected between 2002 and 2009 were selected based on their in vitro susceptibility testing results against ciprofloxacin. In total, 289 C. jejuni and 165 C. coli were collected and analyzed. All ciprofloxacin-resistant isolates had a single mutation (Thr86Ile) in their gyrase A (gyrA) gene and exhibited decreased susceptibility to all eight fluoroquinolones tested. Gatifloxacin, enrofloxacin, and levofloxacin showed greater activity than the other fluoroquinolone drugs in both ciprofloxacin sensitive and -resistant strains. PMID- 28994614 TI - Meta-analysis for the efficacy of S-1-based regimens as the first-line treatment in Asian chemotherapy-naive patients with advanced non-small-cell lung cancer. AB - AIM: We performed a meta-analysis to evaluate the efficacy and safety for S-1 based regimens as the first-line treatment in Asian chemotherapy-naive patients with advanced non-small-cell lung cancer. PATIENTS & METHODS: Eligible randomized clinical trials (RCTs) were included, of which data were extracted by inclusion criteria and exclusion one. Odds ratio and hazard ratio (HR) of outcomes including objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and adverse effects (AEs) were explored for the final analysis. RESULTS: Twenty-one RCTs including 3263 patients were fit into the analysis. Pooled HR for PFS was 1.01 (95% CI: 0.92-1.10; p = 0.88), the pooled HR for OS was 0.95 (95% CI: 0.85-1.06; p = 0.33) and the pooled odds ratio for ORR was 0.74 (95% CI: 0.61-0.90; p = 0.003). S-1-based regimens showed milder AEs in high grade nausea/vomit, anorexia, leukopenia, neutropenia and febrile neutropenia (all p < 0.05). CONCLUSION: The present study has revealed that S-1-based regimens are accompanied by the similar efficacy and slighter AEs compared with standard regimens as the first-line treatment in Asian chemotherapy-naive patients with advanced non-small-cell lung cancer. PMID- 28994616 TI - Assessing speech perception in Swedish school-aged children: preliminary data on the Listen-Say test. AB - To meet the need for a linguistic speech perception test in Swedish, the 'Listen Say test' was developed. Minimal word pairs were used as speech material to assess seven phonetic contrasts in two auditory backgrounds. In the present study, children's speech discrimination skills in quiet and in four-talker (4T) speech background were examined. Associations with lexical-access skills and academic achievement were explored. The study included 27 school children 7-9 years of age. Overall, the children discriminated phonetic contrasts well in both conditions (quiet: Mdn 95%; 4T speech; Mdn 91% correct). A significant effect of 4T speech background was evident in three of the contrasts, connected to place of articulation, voicing and syllable complexity. Reaction times for correctly identified target words were significantly longer in the quiet condition, possibly reflecting a need for further balancing of the test order. Overall speech discrimination accuracy was moderately to highly correlated with lexical access ability. Children identified as having high concentration ability by their teacher had the highest speech discrimination scores in both conditions followed by children identified as having high reading ability. The first wave of data collection with the Listen-Say test indicates that the test appears to be sensitive to predicted perceptual difficulties of phonetic contrasts particularly in noise. The clinical benefit of using a procedure where speech discrimination, lexical-access ability and academic achievement are taken into account is discussed as well as issues for further test refinement. PMID- 28994615 TI - MTRR A66G, RFC1 G80A, and MTHFR C677T and A1298C Polymorphisms and Disease Activity in Mexicans with Rheumatoid Arthritis Treated with Methotrexate. AB - AIM: To investigate the relationships of polymorphisms in genes whose protein products are related in the metabolic pathway of folic acid, particularly MTRR A66G, RFC1 G80A, and MTHFR C677T and A1298C, and disease activity in Mexican patients with rheumatoid arthritis (RA) treated with methotrexate (MTX). MATERIALS AND METHODS: Sixty-eight patients with RA were included in the study who were being treated with MTX, either with or without other drugs. In addition to general data, disease activity was measured by the disease activity score 28 (DAS28). Single nucleotide polymorphisms (SNPs) genotyping was performed by allelic discrimination using real-time polymerase chain reaction. RESULTS: Differences in genotype (homozygotic or heterozygotic for each allele), allele distributions, and phenotype were not statistically different between the RA group and control populations. We did not find any association between the studied polymorphisms and disease activity nor with the intragroup variables (e.g., clinical activity, body mass index, and single- or combined-drug treatment) or between genetic markers; we also did not find any association within the RA group or between the RA group and control populations. CONCLUSION: Additional studies of more polymorphisms related to this or other metabolic pathways are required to determine the influence of genetics on disease activity in RA. PMID- 28994617 TI - An Interim Examination of the US Public Health Response to Ebola. AB - From the summer of 2014 to the spring of 2016, the United States was involved in the Ebola response on both the national and international levels. The United States received 2 imported cases from West Africa and had 2 locally hospital acquired cases, which spurred a massive and unprecedented public health response. As the domestic response stabilized and the epidemic in West Africa slowed, the Association of State and Territorial Health Officials (ASTHO) and the National Association of County and City Health Officials (NACCHO), through a cooperative agreement with the Centers for Disease Control and Prevention (CDC), led an in progress review to assess the national public health response to Ebola. The goal was to identify opportunities to improve the Ebola response and best practices to inform future responses. To inform the review, NACCHO and ASTHO relied on feedback collected from several sources, including a stakeholder meeting held in August 2015, a series of key informant interviews, ASTHO's and NACCHO's internal response assessments, and perspectives shared by state and local health department members and workgroups and national partner organizations. ASTHO and NACCHO engaged experts and practitioners in public health, health care, emergency management, laboratory sciences, environmental health, occupational health, homeland security, communications, and public works from US federal, state, and local governments, the nonprofit community, and private industry. This article summarizes feedback and lessons learned as shared by these sources. Additionally, this article presents recommendations for federal, state, local, and nongovernment partners to improve current and future preparedness and response efforts to infectious disease threats. PMID- 28994618 TI - Pilot evaluation of a coping-oriented supportive program for people with spinal cord injury during inpatient rehabilitation. AB - PURPOSE: To report the feasibility and preliminary effects of a psychosocial care program entitled "coping-oriented supportive program" (COSP) for people with spinal cord injury (SCI) during inpatient rehabilitation. METHODS: This was a pilot test of the COSP using a convenience sample of 22 participants with SCI (11 participants per group) with pre- and post-test, comparison group design. The feasibility, acceptability, and preliminary effects of the COSP were examined. RESULTS: Nine patients with SCI in the intervention group and 11 in the comparison group who completed five or more sessions of the intervention were included in the data analysis. The COSP was feasible with high levels of recruitment, retention and protocol adherence. Good acceptability was suggested by the participants' feedback on the intervention program. The intervention group had a statistically significant greater improvement in self-efficacy (z = -1.978, p = 0.048), life enjoyment and satisfaction (z = -2.801, p = 0.005), and satisfaction of social support (z = -2.298, p = 0.022) at post-test, when compared to the comparison group. Whereas, no significant improvement was found for coping. CONCLUSIONS: Our findings support the feasibility and acceptability of the COSP, and suggest that this intervention is a promising psychosocial care program to enhance people's life satisfaction and well-being as well as the satisfaction of social support after SCI. Further testing of this program with a larger-sized and diverse sample of people with SCI is needed. Implications for Rehabilitation The Chinese culturally-sensitive psychosocial care program (coping oriented supportive program) is feasible, and has the potential to enhance people's self-efficacy in coping with spinal cord injury, and improve their psychosocial well-being and life satisfaction. The conventional inpatient spinal cord injury rehabilitation services could be improved by providing this "first line" psychosocial care program in line with the current medical rehabilitation service. PMID- 28994619 TI - Biological evaluation of benzosuberones. AB - INTRODUCTION: Several natural products containing benzosuberone moiety are clinically reported as anti-tumor agents. Furthermore, several synthetic benzosuberones cited in this review exhibited wide range of theraputic activities such as bacteriostatic, anti-inflammatory, antidepressants and anti-tumor activities. Our recent review provides an overview of the different methods to synthesize the benzosuberones and their extensive biological activities. Areas covered: Thirty-two patents among 130 references are cited in this review that covered the recent inhibitory activities of the benzosuberone scaffolds and their broad area of biological applications up to the first quarter of 2017. The areas covered included anti-inflammatory, antimicrobial, antitumor, selective estrogen receptor, anti-obesity, beta-amyloid production, enzymes and HCV inhibitors in addition to anti-Alzheimer and anti-tuberculosis activities as well as several receptors antagonists. Expert opinion: It is important for medical and pharmaceutical researchers to prepare the first intensive review article concerning the highly biologically active benzosuberone derivatives where they are potent anti-inflammatory, immunosuppressive, antitumor activities and inhibitors of several enzymes. They are useful for treating abnormalities such as sleep disorders, eating disorders and reproductive disorders. Some of these compounds have potential as vascular disrupting agents to selectively target microvessels feeding tumors and some were potential leads for the development of promising therapeutic drugs. PMID- 28994620 TI - PTSD symptoms associated with myocardial infarction: practical clinical implications. AB - OBJECTIVES: Several studies have demonstrated a link between post-traumatic stress disorder and myocardial infarction. We aim to determine what phenotypic features or symptom profile associated with cardiovascular disease may help with early detection and intervention. METHODS: This is a cross-sectional study. The study population comprises trauma-exposed Vietnam War veterans. RESULTS: Variables significantly associated with myocardial infarction from the bivariate analysis were avoidance memories, avoidance reminders and sleep disturbance. These variables were put into a logistic regression with known risk factors for myocardial infarction. Only sleep disturbance retained its effect, with a p-value of 0.015. CONCLUSIONS: It is concluded that sleep disturbance may be a modifiable risk factor in the treatment and prevention of myocardial infarction. PMID- 28994622 TI - Characteristics and correlates of coping with multiple sclerosis: a systematic review. AB - PURPOSE: The purpose of this systematic review was to examine coping strategies that people with multiple sclerosis use, and to identify factors that influence their coping pattern. METHOD: This systematic review followed the Joanna Briggs Institute guidelines for synthesizing descriptive quantitative research. The following databases were searched from the inception of databases until December 2016: Ovid (Medline, Embase, CINAHL, and PsycINFO), Science Direct, Web of Science, and Scopus. Manual search was also conducted from the reference lists of retrieved articles. Findings related to the patterns of coping with multiple sclerosis and factors influencing coping with multiple sclerosis were extracted and synthesized. RESULTS: The search of the database yielded 455 articles. After excluding duplicates (n = 341) and studies that did not meet the inclusion criteria (n = 27), 71 studies were included in the full-text review. Following the full-text, a further 21 studies were excluded. Quality appraisal of 50 studies was completed, and 38 studies were included in the review. Synthesis of findings indicated that people with multiple sclerosis use emotional and avoidance coping strategies more than other types of coping, particularly in the early stages of the disease. In comparison to the general population, people with multiple sclerosis were less likely to use active coping strategies and used more avoidance and emotional coping strategies. The pattern of coping with multiple sclerosis was associated with individual, clinical and psychological factors including gender, educational level, clinical course, mood and mental status, attitude, personality traits, and religious beliefs. CONCLUSIONS: The findings of this review suggest that considering individual or disease-related factors could help healthcare professionals in identifying those less likely to adapt to multiple sclerosis. This information could also be used to provide client centered rehabilitation for people living with multiple sclerosis based on their individual responses and perceptions for coping. Implications for rehabilitation Engagement in coping with multiple sclerosis has been associated with individual factors and neuropsychological functions. Considering individual and disease related factors would allow healthcare professionals to provide more tailored interventions to maintain and master coping with multiple sclerosis. People living with multiple sclerosis should be empowered to appraise and manage ability to cope based on the contextual evidence (individual and clinical condition). Rehabilitation services should move beyond physical management incorporating behavioral aspects for better functioning in living with multiple sclerosis. PMID- 28994621 TI - A rare anomalous origin of right vertebral artery with double branch: First case report. AB - Vertebral artery origin anomalies are typically incidental findings during angiography. We present an extremely rare variant in which the right vertebral artery has a double origin from the right subclavian artery and right common carotid artery in association with an aberrant right subclavian artery, which has never been reported before. PMID- 28994623 TI - Exploring functional outcomes and allied health staffing levels in an inpatient paediatric rehabilitation unit. AB - PURPOSE: This study provides data from a paediatric tertiary hospital on the length of stay, functional improvement and allied health workload for children and adolescents on active inpatient rehabilitation programs. METHODS: An audit was conducted of records of patients managed through an inpatient rehabilitation program at a 359 bed tertiary children's hospital in Brisbane, Australia between December 2014 and December 2015. Data relating to diagnosis, length of stay, functional change, occasions of allied health service and hours of patient attributable allied health professional time were collected. RESULTS: Data on 94 children and adolescents with a total of 102 rehabilitation episodes of care were sourced. The greatest average length of stay was for the "Stroke" group. The highest average allied health professional contact hours were for the "Brain Dysfunction - Traumatic" group. The greatest average functional change was observed in the "Brain Dysfunction- Traumatic group." Physiotherapy accounted for the largest proportion of allied health professional service time, with an average of 32% of total time. CONCLUSIONS: This review from a tertiary hospital based inpatient paediatric rehabilitation service provides information regarding the length of stay, functional change and allied health workload for children and adolescents on active inpatient rehabilitation programs. As expected, total and rehabilitation episode length of stay, functional improvement and allied health contact and input varied according to diagnostic groups. This information is likely to be of value to other Paediatric Rehabilitation Medicine inpatient units when developing staffing for services and benchmarking service delivery. Implications for Rehabilitation Paediatric Rehabilitation Medicine supports children and adolescents to achieve the highest level possible of physical, cognitive, psychological and social functioning following accident or injury. There are little data in the literature to inform the optimal allied health staffing levels required for intensive inpatient multidisciplinary for children and adolescents suffering acquired neurological impairments. Data from this tertiary hospital-based paediatric inpatient rehabilitation program provide information on the length of stay, functional improvement and allied health professional contact for patients across broad diagnostic groupings. This information is useful for other paediatric rehabilitation services when planning for allied health staffing in service development. PMID- 28994624 TI - Plasma heparanase is associated with blood glucose levels but not urinary microalbumin excretion in type 2 diabetic nephropathy at the early stage. AB - AIM: To explore the possible correlations between plasma heparanase and albuminuria, glucose and lipid metabolism in the type 2 diabetic nephropathy patients at the early stage. METHODS: One hundred and forty patients with type 2 diabetic nephropathy at early stage were recruited into the study. Plasma heparanase and the characterized advanced glycation end products (AGEs), carboxymethyllysine (CML) were measured by enzyme-linked immunosorbent assay. RESULTS: Plasma heparanase was positively associated with fasting blood glucose (R = 0.24, p = .01) while heparanase was not significantly correlated with the urinary microalbumin to creatinine ratio (urinary mAlb/Cr) (R = 0.05, p = .58) and CML (R = 0.16, p = .26). On stepwise linear regression analysis, fasting blood glucose was the main independent determinants of plasma heparanase concentration. CONCLUSION: Plasma heparanase is not significantly associated with urinary mAlb/Cr while it is correlated positively with blood glucose levels in the early stage of diabetic nephropathy. Plasma heparnase might be regarded as a marker for vascular endothelial cells injury in diabetic patients. PMID- 28994625 TI - The letter knowledge assessment tool. AB - PURPOSE: There is a need to develop letter knowledge assessment tools to characterise the letter knowledge in Portuguese pre-schoolers and to compare it with pre-schoolers from other countries, but there are no tools for this purpose in Portugal. The aim of this paper is to describe the development and validation procedures of the Prova de Avaliacao de Competencias de Pre-Literacia (PACPL), which assesses letter knowledge. METHOD: This study includes data that has been gathered in two phases: pilot and main study. In the pilot study, an expert panel of six speech and language pathologists analysed the instrument. Children (n = 216) aged 5;0-7;11 participated in the main study that reports data related to the psychometric characteristics of the PACPL. Content validity, internal consistency, reliability and contributing factors to performance were examined statistically. RESULTS: A modified Bland-Altman method revealed good agreement amongst evaluators. The main study showed that the PACPL has a very good internal consistency and high inter-rater (96.2% of agreement and a Cohen's k value of 0.92) and intra-rater (95.6% of agreement and a Cohen's k value of 0.91) agreement. Construct validity of the PCAPL was also assured (Cronbach's alpha of 0.982). Significant differences were found between age groups with children increasing their letter knowledge with age. In addition, they were better at identifying than at producing both letter names and letter sounds. CONCLUSIONS: The PACPL is a valid and reliable instrument to assess letter knowledge in Portuguese children. PMID- 28994627 TI - myBrain: a novel EEG embedded system for epilepsy monitoring. AB - The World Health Organisation has pointed that a successful health care delivery, requires effective medical devices as tools for prevention, diagnosis, treatment and rehabilitation. Several studies have concluded that longer monitoring periods and outpatient settings might increase diagnosis accuracy and success rate of treatment selection. The long-term monitoring of epileptic patients through electroencephalography (EEG) has been considered a powerful tool to improve the diagnosis, disease classification, and treatment of patients with such condition. This work presents the development of a wireless and wearable EEG acquisition platform suitable for both long-term and short-term monitoring in inpatient and outpatient settings. The developed platform features 32 passive dry electrodes, analogue-to-digital signal conversion with 24-bit resolution and a variable sampling frequency from 250 Hz to 1000 Hz per channel, embedded in a stand-alone module. A computer-on-module embedded system runs a Linux(r) operating system that rules the interface between two software frameworks, which interact to satisfy the real-time constraints of signal acquisition as well as parallel recording, processing and wireless data transmission. A textile structure was developed to accommodate all components. Platform performance was evaluated in terms of hardware, software and signal quality. The electrodes were characterised through electrochemical impedance spectroscopy and the operating system performance running an epileptic discrimination algorithm was evaluated. Signal quality was thoroughly assessed in two different approaches: playback of EEG reference signals and benchmarking with a clinical-grade EEG system in alpha-wave replacement and steady-state visual evoked potential paradigms. The proposed platform seems to efficiently monitor epileptic patients in both inpatient and outpatient settings and paves the way to new ambulatory clinical regimens as well as non-clinical EEG applications. PMID- 28994626 TI - PRogram In Support of Moms (PRISM): a pilot group randomized controlled trial of two approaches to improving depression among perinatal women. AB - PURPOSE: This pilot study was designed to inform a larger effectiveness trial by: (1) assessing the feasibility of the PRogram In Support of Moms (PRISM) and our study procedures; and, (2) determining the extent to which PRISM as compared to an active comparison group, the Massachusetts Child Access Psychiatry Program (MCPAP) for Moms alone, improves depression among perinatal women. METHODS: Four practices were randomized to either PRISM or MCPAP for Moms alone, a state-wide telephonic perinatal psychiatry program. PRISM includes MCPAP for Moms plus implementation assistance with local champions, training, and implementation of office prompts and procedures to enhance depression screening, assessment and treatment. Patients with Edinburgh Postnatal Depression Scales (EPDS) >= 10 were recruited during pregnancy, and completed the EPDS and a structured interview at baseline and 3-12 weeks' postpartum. RESULTS: Among MCPAP for Moms alone practices, patients' (n = 9) EPDS scores improved from 15.22 to 10.11 (p = 0.010), whereas in PRISM practices patients' (n = 21) EPDS scores improved from 13.57 to 6.19 (p = 0.001); the between groups difference-of-differences was 2.27 (p = 0.341). CONCLUSIONS: PRISM was beneficial for patients, clinicians, and support staff. Both PRISM and MCPAP for Moms alone improve depression symptom severity and the percentage of women with an EPDS >10. The improvement difference between groups was not statistically significant due to limited power associated with small sample size. PMID- 28994629 TI - High-resolution CT evaluation of bronchial lumen to vertebral body, pulmonary artery to vertebral body and bronchial lumen to pulmonary artery ratios in Dirofilaria immitis-infected cats with and without selamectin administration. AB - Objectives The bronchial lumen to pulmonary artery (BA) ratio is utilized to evaluate pulmonary pathology on CT images. The BA ratio may be unreliable when changes are present in bronchial and pulmonary arteries concurrently. Bronchial lumen to vertebral body (BV) and pulmonary artery to vertebral body (AV) ratios have been established in normal cats and may serve as an alternative. This study aimed to evaluate the BV, AV and BA ratios in cats before and after infection with Dirofilaria immitis, with and without selamectin administration, and to characterize the distribution of disease. Methods Archived CT images were reviewed from three groups of cats: D immitis-infected untreated (n = 6); infected pretreated with selamectin (n = 6); and uninfected untreated (n = 5). The BV, AV and BA ratios were calculated for all lung lobes for baseline (D0) and day 240 (D240) postinfection. Ratios and percentage change from baseline were compared between lobes and between groups. Results BV and AV ratios were more consistent in identifying abnormalities when disease was present in bronchial and arteries concurrently than BA ratios. Infected untreated cats had significant changes in both BV and AV ratios and percentage change from baseline. Abnormal BV and AV ratios were noted in the infected selamectin group, although less widely distributed. Conclusions and relevance The BV and AV ratios more accurately identified bronchial and pulmonary artery abnormalities in D immitis-infected cats. Both bronchial and pulmonary artery changes were present in infected cats, decreasing the diagnostic application of the BA ratio. Pulmonary artery changes were more widely distributed than bronchial changes in the lung. Heartworm infected cats receiving selamectin had bronchial and pulmonary artery changes but to a lesser extent than untreated heartworm-infected cats. The CT-derived BV and AV ratios are a useful measure to evaluate lung disease of cats. PMID- 28994628 TI - Effects of total flavonoids of sea buckthorn ( Hippophae rhamnoides L.) on cytotoxicity of NK92-MI cells. AB - Sea buckthorn ( Hippophae rhamnoides L.) has multifarious medicinal properties including immunoregulatory effect. The total flavonoids of Hippophae rhamnoides L. (TFH) are the main active components isolated from berries of sea buckthorn. The aim of this study was to evaluate the effects of TFH on the cytotoxicity of NK92-MI cells and its possible mechanisms. NK92-MI cells were treated with TFH (2.5 or 5.0 mg/L) or phosphate-buffered saline (PBS) for 24 h, the cytotoxicity against K562 was detected by measuring the release of lactate dehydrogenase (LDH), expression levels of NCRs (NKp30, NKp44, NKp46) and NKG2D were detected by flow cytometry, and expression levels of perforin and granzyme B were detected by western blot. Cytokine Antibody Arrays with 80 cytokine proteins were used to profile the effect of TFH on cytokines. Western blot was adopted to detect the effects of TFH on STAT1, STAT4, and STAT5 signal pathway. Compared with the normal control group, TFH could significantly enhance NK92-MI cell cytotoxicity against K562 cells, upregulate expressions of NKp44, NKp46, perforin, and granzyme B. TFH could upregulate expressions of IL-1alpha, IL-2, IL-7, IL-15, CSF 2, CSF-3, MCP-1, MIG, IFN-gamma, TNF-alpha, and TNF-beta and downregulate expressions of IL-16, MIP-1beta, CX3CL-1, and MIF. TFH could increase expressions of phospho-STAT1 and phospho-STAT5. The results suggest that TFH stimulated NK92 MI cells to activate and enhance cytotoxicity of NK92-MI cells. PMID- 28994630 TI - Clinical presentations, treatments and risk factors for mortality in cats with tick paralysis caused by Ixodes holocyclus: 2077 cases (2008-2016). AB - Objectives The objective of this study was to describe seasonality, demographics, presentations, treatments, complications and outcomes for cats with Ixodes holocyclus causing tick paralysis, and to identify risk factors for mortality. Methods This was a retrospective single cohort study with 2077 cases occurring between 2008 and 2016, and presenting to one of four emergency clinics in south eastern Queensland, Australia. Case mortality at 5 days post-presentation could be determined for 1742 cases, and potential risk factors for mortality were assessed using random-effects logistic regression. Results Cases occurred all year round, but there was a marked seasonal pattern with more cases presenting in spring than any other season. Overall, 54/1742 cases (3%) died by 5 days after presentation. Five day mortality incidence for cases that received polyclonal canine tick antitoxin serum (TAS) and recommended treatment was 28/1410 (2%) vs 4/52 (8%) for cases that did not receive TAS ( P <0.001). Mechanical ventilation was recommended for 131/2077 cases (6%). Where mechanical ventilation was recommended but not implemented, mortality incidence was 15/17 (88%), whereas 4/22 cases (18%) that received mechanical ventilation died by day 5. From multivariable analyses, initial gait score (overall P = 0.047) and body temperature on presentation (overall P <0.001) were independently associated with mortality; cases with higher gait scores and those with body temperatures <35 degrees C were at greater risk of death. Cases that had an adverse reaction to TAS were also more likely to die ( P = 0.002). Additional ticks were detected at coat clipping for 80/872 (9%) the cases that were clipped, and coat clipping was associated with a reduced risk of mortality ( P = 0.020). Risk of mortality did not differ significantly by time of year, clinic location, breed, sex, neuter status, age, weight, coat length or number of ticks found. Conclusions and relevance The overall mortality risk for cats treated for tick paralysis caused by I holocyclus is low. Risk factors for mortality include advanced gait and respiratory scores, and hypothermia at presentation. Coat clipping and TAS reduce the risk of mortality, whereas the occurrence of a TAS reaction increases the risk. Mechanical ventilation reduces mortality risk in cats with respiratory failure due to tick paralysis. PMID- 28994631 TI - Health Care Resource Utilization for Outpatient Cardiovascular Disease and Diabetes Care Delivery Among Advanced Practice Providers and Physician Providers in Primary Care. AB - Although effectiveness of diabetes or cardiovascular disease (CVD) care delivery between physicians and advanced practice providers (APPs) has been shown to be comparable, health care resource utilization between these 2 provider types in primary care is unknown. This study compared health care resource utilization between patients with diabetes or CVD receiving care from APPs or physicians. Diabetes (n = 1,022,588) or CVD (n = 1,187,035) patients with a primary care visit between October 2013 and September 2014 in 130 Veterans Affairs facilities were identified. Using hierarchical regression adjusting for covariates including patient illness burden, the authors compared number of primary or specialty care visits and number of lipid panels and hemoglobinA1c (HbA1c) tests among diabetes patients, and number of primary or specialty care visits and number of lipid panels and cardiac stress tests among CVD patients receiving care from physicians and APPs. Physicians had significantly larger patient panels compared with APPs. In adjusted analyses, diabetes patients receiving care from APPs received fewer primary and specialty care visits and a greater number of lipid panels and HbA1c tests compared with patients receiving care from physicians. CVD patients receiving care from APPs received more frequent lipid testing and fewer primary and specialty care visits compared with those receiving care from physicians, with no differences in the number of stress tests. Most of these differences, although statistically significant, were numerically small. Health care resource utilization among diabetes or CVD patients receiving care from APPs or physicians appears comparable, although physicians work with larger patient panels. PMID- 28994632 TI - Firearm Projectile in the Maxillary Tuberosity Located by Adjunctive Examination of Wide-Field Optical Fluorescence. AB - OBJECTIVE: Demonstrate the use of wide-field optical fluorescence as an adjunctive examination in a clinical routine to oral diagnosis. BACKGROUND DATA: Use of wide-field optical fluorescence in the oral cavity has been restricted to topics related to the detection and diagnosis of oral cancer. MATERIALS AND METHODS: In a regular medical appointment, a 58-year-old female patient, without any complaint or oral symptom, underwent the complementary examination by wide field optical fluorescence. A device with high-power light-emitting diode emitting light centered at a wavelength of (400 +/- 10) nm and maximum irradiance of (0.040 +/- 0.008) W/cm2 was used for fluorescence visualization. RESULTS: We report the location of a firearm projectile, intraosseous, in the maxillary tuberosity using wide-field optical fluorescence. CONCLUSIONS: It is evidenced that wide-field optical fluorescence, within a clinical routine, can provide relevant images and data, with an immediate result, without the use of ionizing radiation, enabling an efficient oral diagnosis. PMID- 28994633 TI - Endovascular aneurysm repair in the elderly: First do no harm. AB - Endovascular aneurysm repair (EVAR) has become the intervention of choice for supra-threshold aortic aneurysms due to the lower 30-day mortality of EVAR as compared with open surgery, despite no long-term longevity gains. Trials such as EVAR-1 that established the current status of endovascular aortic intervention often excluded participants over the age of 80, and specific studies of EVAR in the elderly reveal higher mortality than accepted averages. Analyses of the cost effectiveness of EVAR have not demonstrated superiority of endovascular intervention over open repair, in particular when considering complications such as endoleak. Post-intervention surveillance and the frequent need for re intervention following EVAR has a detrimental impact on quality of life. Taking these factors into consideration, combined with an ageing population and the likely increase in octogenarian endovascular intervention, there is a clear clinical need for appropriate risk-stratification of elderly patients with supra threshold aneurysms to determine who will benefit from endovascular repair. PMID- 28994634 TI - The EU project "United4Health": Results and experiences from automatic health status assessment in a Norwegian telemedicine trial system. AB - Introduction Patients with chronic obstructive pulmonary disease require help in daily life situations to increase their individual perception of security, especially under worsened medical conditions. Unnecessary hospital (re )admissions and home visits by doctors or nurses shall be avoided. This study evaluates the results from a two-year telemedicine field trial for automatic health status assessment based on remote monitoring and analysis of a long time series of vital signs data from patients at home over periods of weeks or months. Methods After discharge from hospital treatment for acute exacerbations, 94 patients were recruited for follow-up by the trial system. The system supported daily measurements of pulse and transdermal peripheral capillary oxygen saturation at patients' homes, a symptom-specific questionnaire, and provided nurses trained to use telemedicine ("telenurses") with an automatically generated health status overview of all monitored patients. A colour code (green/yellow/red) indicated whether the patient was stable or had a notable deterioration, while red alerts highlighted those in most urgent need of follow up. The telenurses could manually overwrite the status level based on the patients' conditions observed through video consultation. Results Health status evaluation in 4970 telemonitor datasets were assessed retrospectively. The automatic health status determination (subgroup of 33 patients) showed green status at 46% of the days during a one-month monitoring period, 28% yellow status, and 19% red status (no data reported at 7% of the days). The telenurses manually downrated approximately 10% of the red or yellow alerts. Discussion The evaluation of the defined real-time health status assessment algorithms, which involve static rules with personally adapted elements, shows limitations to adapt long-term home monitoring with adequate interpretation of day-to-day changes in the patient's condition. Thus, due to the given sensitivity and specificity of such algorithms, it seems challenging to avoid false high alerts. PMID- 28994636 TI - Meetings Calendar 2017. PMID- 28994637 TI - Cortical lesions and HLA genotype: Still a grey area? PMID- 28994635 TI - Does Isolation of Enterococcus Affect Outcomes in Intra-Abdominal Infections? AB - BACKGROUND: Enterococci are isolated frequently as pathogens in patients with intra-abdominal infections (IAIs) and may predict poor clinical outcomes. It remains controversial whether enterococci warrant an altered treatment approach with regard to antimicrobial treatment. PATIENTS AND METHODS: The study population was derived from the Study to Optimize Peritoneal Infection Therapy (STOP-IT) trial database. Through post hoc analysis subjects were stratified into two groups based on isolation of Enterococcus. Fifty subjects of the cohort (n = 518) had Enterococcus isolated. Uni-variable and multi-variable analyses were conducted to determine whether isolation of Enterococcus constituted an independent predictor of the pre-defined STOP-IT composite outcome (surgical site infection, recurrent IAI, or death) and the individual components of the composite outcome. RESULTS: From the cohort of 50 subjects, we identified 52 isolates of Enterococcus spp. with a predominance of Enterococcus faecalis (40%) followed by other Enterococcus spp. (37%) and Enterococcus faecium (17%). Baseline demographic characteristics were statistically similar between the two groups. Antibiotic utilization distribution remained balanced between the Enterococcus and no Enterococcus groups with the majority receiving piperacillin tazobactam (62% and 54%, respectively). The groups had comparable infection characteristics including setting of acquisition (>50% community acquired) and origin of infection (predominantly colon or rectum). Individual and composite clinical outcomes were not different statistically between the Enterococcus and no Enterococcus groups: surgical site infection (10% vs. 7.5%; p = 0.53), recurrent IAI (20% vs. 14.1%; p = 0.26), death (2% vs. 1%; p = 0.40), and composite of all three (30% vs. 20.9%; p = 0.14], respectively. Multi-variable analysis revealed that isolation of Enterococcus did not predict independently the incidence of the composite outcome (odds ratio [OR] 1.53 [95% confidence interval {CI} = 0.78-3.01]; p = 0.22; c-statistic = 0.65; goodness of fit, p = 0.71). CONCLUSIONS: Enterococcus was not a more common pathogen in health-care associated IAIs and was not an independent risk factor for the composite outcome. The isolation of Enterococcus from IAIs may not warrant an alternative treatment approach but larger studies are needed to validate these findings. PMID- 28994638 TI - Dendrimers, Carotenoids, and Monoclonal Antibodies. AB - Dendrimers are unimolecular architectural nano- or microparticle entities that can accommodate various nutraceuticals and pharmaceuticals between their branches (dendrons) and provide targeted delivery of biomimetics into different tissues upon addition of functionalized groups to the dendrimer's surface. Covalent binding, hydrogen bonds, and electrostatic interactions between dendrimer composing molecules are known to form and stabilize dendrimer structure. Carotenoids have recently been shown to form dendrimer-like structures and promote targeted delivery of "cargo" molecules into organs characterized by high carotenoid uptake (adrenal glands, prostate, liver, and brain). The use of carotenoid dendrimers, in particular lycosome particles loaded with various xenobiotics (resveratrol, cocoa flavanols, and HMG-CoA reductase inhibitors), reportedly has a beneficial effect in diabetic foot syndrome, prehypertension, and cardiovascular disease. New applications for carotenoid dendrimers may arise from the use of complexes formed by carotenoid dendrimers and monoclonal antibodies (mAbs). The internalization of carotenoid dendrimer-mAb complexes through receptor-mediated mechanisms may prevent interactions of dendrimer incorporated xenobiotics with membrane-associated P-glycoprotein, a major factor of drug resistance in tumor cells. The incorporation of mAb fragments with higher binding capacity to the membrane receptors and higher affinity to the target molecule may further increase the bioavailability of "cargo" molecules transported by the carotenoid dendrimer-mAb complexes and open new doors in nanodelivery technologies. PMID- 28994639 TI - Migraine, menopause and hormone replacement therapy. AB - Perimenopause marks a period of increased migraine prevalence in women and many women also report troublesome vasomotor symptoms. Migraine is affected by fluctuating estrogen levels with evidence to support estrogen 'withdrawal' as a trigger of menstrual attacks of migraine without aura, while high estrogen levels can trigger migraine aura. Maintaining a stable estrogen environment with estrogen replacement can benefit estrogen-withdrawal migraine particularly in women who would also benefit from relief of vasomotor symptoms. In contrast to contraceptive doses of ethinylestradiol, migraine aura does not contraindicate use of physiological doses of natural estrogen. In women with migraine with or without aura, using only the lowest doses of transdermal estrogen necessary to control vasomotor symptoms minimizes the risk of unwanted side effects. Cyclical progestogens can have an adverse effect on migraine so continuous progestogens, as provided by the levonorgestrel intrauterine system or in continuous combined transdermal preparation, are preferred. There are no data on the effect of micronized progesterone on migraine, either cyclical or continuous. Non-hormonal options for both conditions are limited but there is evidence of efficacy for escitalopram and venflaxine. PMID- 28994640 TI - Serum symmetric dimethylarginine and creatinine in Birman cats compared with cats of other breeds. AB - Objectives The aim of this study was to assess whether, in contrast to serum creatinine, which is higher in Birman cats than in other breeds, the serum concentration of symmetric dimethylarginine (SDMA) is comparable in clinically healthy Birmans and in the general feline population. This could allow, in this breed, to better evaluate chronic kidney disease (CKD). Methods Serum creatinine and SDMA were measured in clinically healthy Birmans (n = 50) and in cats of other breeds (n = 46), and the results were statistically compared. A breed specific reference interval (RI) was established for Birmans and compared with the RI for the general feline population (0.0-14.0 ug/dl). Results Creatinine (1.58 +/- 0.36 mg/dl) and SDMA (12.2 +/- 2.8 ug/dl) were higher ( P <0.001) in Birmans than in cats of other breeds (1.19 +/- 0.17 mg/dl; 10.3 +/- 2.5 ug/dl). In 20/50 Birman cats (40.0%) serum creatinine was higher than both the non-breed specific RI of our laboratory and the threshold recommended to classify cats as IRIS stage 2 (1.6 mg/dl). The concentration of SDMA was higher than the pre existing RI in 10/50 Birmans (20.0%) and in four cats of other breeds (8.7%). Among Birmans, the proportion of cats with SDMA >14 ug/dl was lower ( P <0.017) than the proportion of cats with creatinine >1.60 mg/dl. However, the deviation from the upper limit of the RI was lower than the analytical variability of the method in 7/10 Birmans and in 4/4 cats of other breeds. The breed-specific RI (3.5-18.7 ug/dl) overlapped with the pre-existing one. Conclusions and relevance SDMA may be a better marker of CKD in Birman cats than creatinine when non-breed specific RIs are utilised. The coupled analysis of creatinine and SDMA could help prevent errors in diagnosing and staging CKD in Birman cats. PMID- 28994641 TI - HLA genotype and cortical lesions: Response to the letter from Spencer et al. PMID- 28994642 TI - Reasons for Not Treating Women with Postmenopausal Osteoporosis with Prescription Medications: Physicians' and Patients' Perspectives. AB - BACKGROUND: In the United States, between one-third and two thirds of postmenopausal women do not begin treatment with a prescription osteoporosis medication after a diagnosis of osteoporosis. The objective of this study was to understand the reasons for this lack of treatment. MATERIALS AND METHODS: Online physician and patient surveys were administered in 2013. The physician survey included a chart review of untreated postmenopausal women recently diagnosed with osteoporosis and gathered data on physicians' practices regarding the management of osteoporosis in postmenopausal women. The patient survey was given to untreated postmenopausal women with a recent osteoporosis diagnosis. RESULTS: The physician survey was completed by 224 physicians, who also reviewed 811 patient charts. A total of 165 patients completed the patient survey. In the chart review, physicians reported that 19% of the postmenopausal women they diagnosed with osteoporosis were not prescribed an osteoporosis medication. The patient declined a physician's recommendation for pharmacological treatment in 81% and 52% of cases in the physician and patient surveys, respectively. The most frequent reasons for physicians not recommending treatment were: low calcium and/or vitamin D levels, patients potentially at risk of medication side effects, pre-existing gastrointestinal problems, and polypharmacy. The most frequent reasons for patients deciding against treatment were: concerns about side effects, considering nonprescription options and behavioral modifications, and questioning the potential benefit of taking the medication. CONCLUSIONS: Patients decided against pharmacological treatment of newly diagnosed osteoporosis in at least half of the cases of nontreatment. The principal reasons for not being treated with a prescription medication, given by both physicians and patients, were that there were alternatives and concern about the risks of prescription medications. PMID- 28994644 TI - Belgian Society of Cardiology Belgian Heart Rhythm Association (BeHRA). PMID- 28994643 TI - Shorter Treatment Intervals of East Asians with Port-Wine Stain with Pulsed Dye Laser Are Safe and Effective-A Prospective Side-by-Side Comparison. AB - OBJECTIVE: To compare the safety and efficacy of pulsed dye laser (PDL) at different intervals for the treatment of East Asians with Port-Wine Stain (PWS). BACKGROUND: The population of East Asians around the world is about 1.6 billion, and they are considered to have more melanin in their skin compared with Caucasians. Nevertheless, no studies about the optimal treatment intervals for East Asians with PWS have been carried out. METHODS: We prospectively investigated 39 East Asian patients with untreated PWS. Half of the PWS lesion was randomly allocated to be treated at 3 weeks and the other half at 6 weeks. Both halves of the PWS were treated three times in total. The efficacy outcome 2 months post final treatment was evaluated by visual and chromameter evaluation. RESULTS: The average blanching rate was 40.27% and 44.17% for PDL treatments at the 3- and 6-week interval sites, respectively (p > 0.05). No patient developed scarring or permanent pigmentation change. LIMITATIONS: There was no age criteria involved in the enrollment of patients in this study. Additionally, there is no comparison with long-term treatments at different intervals. CONCLUSIONS: PDL treatment at 3-week interval proved to be safe for East Asians with PWS. This can reduce the total duration of the course of treatments and had no increase in side effects compared with the standard interval treatments. PMID- 28994645 TI - Risky Sexual Behavior of Senior Secondary School Students in an Urban Community of Oyo State, South West Nigeria. AB - BACKGROUND: Young people worldwide are now at increased risk of unsafe sexual behavior; it is thus imperative to understand the determinants of such practices among them. STUDY OBJECTIVE: To assess factors associated with Risky Sexual Behavior (RSB) among secondary school students in Nigeria. METHODOLOGY: This cross-sectional study was conducted using multistage sampling technique among 375 secondary school students in Ogbomoso, Nigeria. A pretested questionnaire was used for data collection; chi-square test and binary logistic regression analysis were done. RESULT: Overall, 23.0% of the respondents had at least one RSB; students not in steady relationships were 5 times more likely to have RSB ( OR = 4.50, 95% CI [2.66, 7.71]). Also, respondents who had positive attitude toward RSB had 24% increased odds of RSB practice compared with those with negative attitude ( OR = 23.75, 95%CI [2.48, 22.78]). CONCLUSION: The burden of RSB is high among secondary school students in South West Nigeria. There is urgent need for reprogramming of sex education for the Nigerian secondary school students. PMID- 28994646 TI - Envisioning Eye Care From a Rural Perspective: A Photovoice Project From India. AB - Background To understand barriers and promoters for accessing eye care by rural communities, we used a modified approach to Photovoice, a community-based participatory action research approach Methods Community members took photographs and wrote or spoke stories based upon a series of questions intended to facilitate deeper thinking. Fifteen rural paramedical team members who were affiliated with the rural network of L V Prasad Eye Institute, and 60 people from four villages reported barriers and promoters for eye care access for 20 villages Results Important barriers for accessing eye care included the following: no caretaker at home for grandchildren except for the grandparent(s), alcoholism, uncontrolled blood pressure, inadequate diabetes management, lack of escort for blind people and elders, affordability, and inadequate clinic staffing during summer season when farming villagers were available. Important promoters for seeking eye care included having a neighbor who had a good surgical outcome in one eye which resulted in the ability to resume work. The Photovoice project offered specific suggestions to hospital management for improving eye care access, including providing evening transportation, providing additional surgical staffing during busy summer season, and the creation of tool spectacle repair kits to be kept at the primary vision centers Conclusions This Photovoice project facilitated a deeper understanding of the important barriers and promoters for accessing eye care by villagers, and by the rural eye care team, offering specific suggestions to hospital management for improving eye care access and to communicate without any inhibiting factors like fear of hierarchy within the hospital administration. PMID- 28994647 TI - Factors Influencing the Initiation of Smokeless Tobacco Consumption Among Low Socioeconomic Community in Bangladesh: A Qualitative Investigation. AB - This study explored factors influencing the initiation of smokeless tobacco (SLT) consumption in a low socioeconomic urban community in Bangladesh. The study conducted four focus group discussions among 33 informants involves school teachers, community leaders, women, and betel-nut shops owners. The results were prepared by thematic analysis of the transcripts where informants mean age was 30 ( SD +/- 6.8) years with varying level of education. Tradition of hospitality, curiosity, offer from an elderly person, and avoiding nausea during pregnancy and at time of quitting smoking were key factors for the initiation of SLT consumption. The results also revealed most people were aware about the danger of SLT consumption but, in practice, consumed frequently. The research suggested that doctors might advise people not to use any form of SLT while they seeking health services. Furthermore, community-based awareness program could minimize the wider use of SLT among low-income community in Bangladesh. PMID- 28994648 TI - Smokeless tobacco (snus) use and colorectal cancer incidence and survival: Results from nine pooled cohorts. AB - AIMS: Although smoking is considered to be an established risk factor for colorectal cancer, the current evidence on the association between smokeless tobacco and colorectal cancer is scant and inconclusive. We used pooled individual data from the Swedish Collaboration on Health Effects of Snus Use to assess this association. METHODS: A total of 417,872 male participants from nine cohort studies across Sweden were followed up for incidence of colorectal cancer and death. Outcomes were ascertained through linkage to health registers. We used shared frailty models with random effects at the study level to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During 7,135,504 person years of observation, 4170 men developed colorectal cancer. There was no clear association between snus use and colorectal cancer overall. Exclusive current snus users, however, had an increased risk of rectal cancer (HR 1.40: 95% CI 1.09, 1.79). There were no statistically significant associations between snus use and either all-cause or colorectal cancer-specific mortality after colorectal cancer diagnosis. CONCLUSIONS: Our findings, from a large sample, do not support any strong relationships between snus use and colorectal cancer risk and survival among men. However, the observed increased risk of rectal cancer is noteworthy, and in merit of further attention. PMID- 28994649 TI - Planar cell polarity signaling coordinates oriented cell division and cell rearrangement in clonally expanding growth plate cartilage. AB - Both oriented cell divisions and cell rearrangements are critical for proper embryogenesis and organogenesis. However, little is known about how these two cellular events are integrated. Here we examine the linkage between these processes in chick limb cartilage. By combining retroviral-based multicolor clonal analysis with live imaging, the results show that single chondrocyte precursors can generate both single-column and multi-column clones through oriented division followed by cell rearrangements. Focusing on single column formation, we show that this stereotypical tissue architecture is established by a pivot-like process between sister cells. After mediolateral cell division, N cadherin is enriched in the post-cleavage furrow; then one cell pivots around the other, resulting in stacking into a column. Perturbation analyses demonstrate that planar cell polarity signaling enables cells to pivot in the direction of limb elongation via this N-cadherin-mediated coupling. Our work provides new insights into the mechanisms generating appropriate tissue architecture of limb skeleton. PMID- 28994650 TI - CDK9-dependent RNA polymerase II pausing controls transcription initiation. AB - Gene transcription can be activated by decreasing the duration of RNA polymerase II pausing in the promoter-proximal region, but how this is achieved remains unclear. Here we use a 'multi-omics' approach to demonstrate that the duration of polymerase pausing generally limits the productive frequency of transcription initiation in human cells ('pause-initiation limit'). We further engineer a human cell line to allow for specific and rapid inhibition of the P-TEFb kinase CDK9, which is implicated in polymerase pause release. CDK9 activity decreases the pause duration but also increases the productive initiation frequency. This shows that CDK9 stimulates release of paused polymerase and activates transcription by increasing the number of transcribing polymerases and thus the amount of mRNA synthesized per time. CDK9 activity is also associated with long-range chromatin interactions, suggesting that enhancers can influence the pause-initiation limit to regulate transcription. PMID- 28994653 TI - TAVI risk scoring using established versus new scoring systems: role of the new STS/ACC model. AB - AIMS: The aim of this study was to validate the recently developed STS/ACC TAVR in-hospital mortality risk score for predicting in-hospital mortality after transcatheter aotic valve implantation (TAVI) and to compare its ability to predict 30-day mortality with that of four other established risk models (EuroSCORE I, EuroSCORE II, STS-PROM, and German AV Score). METHODS AND RESULTS: The study cohort included 946 consecutive patients who underwent TAVI between 2013 and 2015. Each of the five scores was fitted as a continuous linear variable into a logistic regression model estimating 30-day mortality. The STS/ACC TAVR score was additionally analysed for in-hospital mortality. C-statistics and likelihood ratio (LR) test p-values were estimated for each model to describe the model fit. The ability of the STS/ACC score to predict in-hospital mortality was similar to the reported STS/ACC TVT registry data (this study's C-statistic 0.65 vs. STS/ACC TVT registry 0.66). The STS-PROM score (C-statistic=0.68; LR p<0.0001) and the new STS/ACC TAVR score (C-statistic=0.68; LR p<0.0001) were superior to the other scores (EuroSCORE I [C-statistic=0.55; LR p=0.02], EuroSCORE II [C-statistic=0.58; LR p=0.02], German AV Score [C-statistic=0.62; LR p<0.01]) for prediction of 30-day mortality. CONCLUSIONS: These data show the superiority of the STS-PROM and STS/ACC TAVR scores compared with other existing risk calculation models in predicting 30-day mortality after TAVI in a German all comers population. The STS/ACC TAVR score, however, is easier to calculate (12 vs. 28 variables), and may thus gain wider acceptance and be accompanied by improved inter-observer reliability. PMID- 28994651 TI - HMMR acts in the PLK1-dependent spindle positioning pathway and supports neural development. AB - Oriented cell division is one mechanism progenitor cells use during development and to maintain tissue homeostasis. Common to most cell types is the asymmetric establishment and regulation of cortical NuMA-dynein complexes that position the mitotic spindle. Here, we discover that HMMR acts at centrosomes in a PLK1 dependent pathway that locates active Ran and modulates the cortical localization of NuMA-dynein complexes to correct mispositioned spindles. This pathway was discovered through the creation and analysis of Hmmr-knockout mice, which suffer neonatal lethality with defective neural development and pleiotropic phenotypes in multiple tissues. HMMR over-expression in immortalized cancer cells induces phenotypes consistent with an increase in active Ran including defects in spindle orientation. These data identify an essential role for HMMR in the PLK1-dependent regulatory pathway that orients progenitor cell division and supports neural development. PMID- 28994654 TI - Impact of concomitant mitral regurgitation on transvalvular gradient and flow in severe aortic stenosis: a systematic ex vivo analysis of a subentity of low-flow low-gradient aortic stenosis. AB - AIMS: Evaluation of aortic stenosis (AS) is based on echocardiographic measurement of mean pressure gradient (MPG), flow velocity (Vmax) and aortic valve area (AVA). The objective of the present study was to analyse the impact of systemic haemodynamic variables and concomitant mitral regurgitation (MR) on aortic MPG, Vmax and AVA in severe AS. METHODS AND RESULTS: A pulsatile circulatory model was designed to study function and interdependence of stenotic aortic (AVA: 1.0 cm2, 0.8 cm2 and 0.6 cm2) and insufficient mitral prosthetic valves (n=8; effective regurgitant orifice area [EROA] <0.2 cm2 vs. >0.4 cm2) using Doppler ultrasound. In the absence of severe MR, a stepwise increase of stroke volume (SV) and a decrease of AVA was associated with a proportional increase of aortic MPG. When MR with EROA <0.2 cm2 vs. >0.4 cm2 was introduced, forward SV decreased significantly (70.9+/-1.1 ml vs. 60.8+/-1.6 ml vs. 47.4+/ 1.1 ml; p=0.02) while MR volume increased proportionally. This was associated with a subsequent reduction of aortic MPG (57.1+/-9.4 mmHg vs. 48.6+/-13.8 mmHg vs. 33.64+/-9.5 mmHg; p=0.035) and Vmax (5.09+/-0.4 m/s vs. 4.91+/-0.73 m/s vs. 3.75+/-0.57 m/s; p=0.007). Calculated AVA remained unchanged (without MR: AVA=0.53+/-0.04 cm2 vs. with MR: AVA=0.52+/-0.05 cm2; p=ns). In the setting of severe AS without MR, changes of vascular resistance (SVR) and compliance (C) did not impact on aortic MPG (low SVR and C: 66+/-13.8 mmHg and 61.1+/-20 mmHg vs. high SVR and C: 60.9+/-9.2 mmHg and 71.5+/-13.5 mmHg; p=ns) In concomitant severe MR, aortic MPG and Vmax were not significantly reduced by increased SVR (36.6+/ 2.2 mmHg vs. 34.9+/-5.6 mmHg, p=0.608; 3.89+/-0.18 m/s vs. 3.96+/-0.28 m/s; p=ns). CONCLUSIONS: Systemic haemodynamic variables and concomitant MR may potentially affect diagnostic accuracy of echocardiographic AS evaluation. As demonstrated in the present study, MPG and Vmax are flow-dependent and significantly reduced by a reduction of forward SV from concomitant severe MR, resulting in another entity of low-flow low-gradient aortic stenosis. In contrast, calculated AVA appears to be a robust parameter of AS evaluation if severe MR is present. Changes of SVR and C did not affect the diagnostic accuracy of AS evaluation. PMID- 28994655 TI - Functional comparison between the BuMA Supreme biodegradable polymer sirolimus eluting stent and a durable polymer zotarolimus-eluting coronary stent using quantitative flow ratio: PIONEER QFR substudy. AB - AIMS: Quantitative flow ratio (QFR) based on three-dimensional quantitative coronary angiography (3D-QCA) is a novel method to assess physiological functionality after treatment with stents. The current study aimed to evaluate the difference in physiological functionality nine months after implantation of a bioresorbable polymer-based sirolimus-eluting stent with an electrografting base layer (BuMA Supreme: B-SES) versus a durable polymer-based zotarolimus-eluting stent (Resolute: R-ZES). METHODS AND RESULTS: The current post hoc analysis was performed in the PIONEER randomised trial (1:1 randomisation to B-SES [83 patients/95 lesions] and R-ZES [87 patients/101 lesions]). QFR was measured in stented vessels in both arms at preprocedural, post-procedural and nine-month angiography without pharmacologically induced hyperaemia (contrast QFR). At nine months, both the values of QFR distal to the stent (B-SES: 0.89+/-0.10 vs. R-ZES: 0.89+/-0.11, p=0.97) and the number of vessels with QFR <=0.8 were not significantly different between the two groups (11.0% vs. 12.8%, p=0.72), while the in-stent binary restenosis rate was also comparable (3.7% vs. 3.5%, p=1.00). QFR gradient across the device (?QFR) at nine months was also similar between the groups (B-SES: 0.03+/-0.04 vs. R-ZES: 0.03+/-0.07, p=0.95). CONCLUSIONS: Quantitative flow assessment nine months after stenting did not differ between B SES and R-ZES, despite a significant difference in in-stent late lumen loss. PMID- 28994656 TI - Videodensitometric quantification of paravalvular regurgitation of a transcatheter aortic valve: in vitro validation. AB - AIMS: Videodensitometric assessment of aortography provides a periprocedural quantitation of prosthetic valve regurgitation (PVR) after transcatheter aortic valve implantation. We sought to compare the videodensitometric parameters of PVR severity to the regurgitation fraction (RF) in a controlled in vitro setting. METHODS AND RESULTS: In a mock circulation system, a transcatheter balloon expandable valve inserted at the aortic valve position was gradually deformed to induce different grades of paravalvular leakage and the RF was measured with a transonic flow probe. Contrast aortography was performed and the following videodensitometric parameters were generated: left ventricle aortic regurgitation (LV-AR), LV outflow tract AR (LVOT-AR), quantitative regurgitation assessment (qRA) index, relative maximum density (relative max), and maximum upslope of the LV time-density curve. The correlation was substantial between videodensitometric parameters (LV-AR, LVOT-AR, qRA index, relative max, and maximum upslope) and RF (r2=0.96, 0.96, 0.93, 0.87, and 0.93; p<0.001 for all). LV-AR (region of interest [ROI]=entire LV) and LVOT-AR (ROI=LVOT) were not different (p=0.51) and were strongly correlated (r2=0.99) with a mean difference of 1.92% (95% limits of agreement: +/-2.83). The correlations of LV-AR and LVOT-AR with RF were stronger when more than one cardiac cycle was included in the analysis (one cycle: r2=0.85 and r2=0.83; four cycles: r2=0.96 and r2=0.96, for LV-AR and LVOT-AR, respectively). Including more cycles beyond four did not improve accuracy. CONCLUSIONS: Quantitative assessment of PVR by videodensitometry of aortograms strongly correlates with the actual RF in a controlled in vitro setting. Accuracy is improved by including more than one cardiac cycle in the analysis. PMID- 28994652 TI - Mechanism of activation at the selectivity filter of the KcsA K+ channel. AB - Potassium channels are opened by ligands and/or membrane potential. In voltage gated K+ channels and the prokaryotic KcsA channel, conduction is believed to result from opening of an intracellular constriction that prevents ion entry into the pore. On the other hand, numerous ligand-gated K+ channels lack such gate, suggesting that they may be activated by a change within the selectivity filter, a narrow region at the extracellular side of the pore. Using molecular dynamics simulations and electrophysiology measurements, we show that ligand-induced conformational changes in the KcsA channel removes steric restraints at the selectivity filter, thus resulting in structural fluctuations, reduced K+ affinity, and increased ion permeation. Such activation of the selectivity filter may be a universal gating mechanism within K+ channels. The occlusion of the pore at the level of the intracellular gate appears to be secondary. PMID- 28994657 TI - Thrombosed mechanical tricuspid valve: emergent valvuloplasty as rescue. PMID- 28994658 TI - Non-invasive treatment planning of tandem coronary artery lesions using an interactive planner for PCI. PMID- 28994659 TI - Our experience training a neurocardiologist: a case for an emerging specialty. PMID- 28994660 TI - Pharmacokinetics of rilpivirine and 24-week outcomes after switching from efavirenz in virologically suppressed HIV-1-infected adolescents. AB - BACKGROUND: Rilpivirine (RPV), a non-nucleoside reverse transcriptase inhibitor drug, could be a favourable drug for maintenance therapy in HIV-infected adolescents because it has few long-term side effects. However, data among adolescents switching from efavirenz (EFV) to RPV are limited. This study investigated the pharmacokinetics (PK), safety and efficacy of RPV in virologically suppressed HIV-1-infected adolescents after switching from EFV. METHODS: Adolescents aged 12-18 years on EFV-based antiretroviral therapy (ART) were switched from EFV to RPV (25 mg, once daily). Intensive 24-h blood samplings at 0 (pre-dose), 1, 2, 4, 5, 6, 9, 12 and 24 h were performed 4 weeks after switching. PK parameters were calculated using a non-compartmental method and compared with published data from the PAINT and pooled ECHO/THRIVE substudies. HIV RNA level was measured at weeks 12 and 24. Biochemical profiles were measured at baseline and week 24. RESULTS: From January to June 2016, 20 adolescents (12 male) were enrolled. Median (IQR) age was 16 (15-17) years and weight was 49 (42 59) kg. Mean (sd) AUC24 h, C24 h and Cmax of RPV were 2,041 (745) ng*h/ml, 69 (29) ng/ml and 143 (65) ng/ml, respectively. Median (IQR) Tmax was 5 (2-9) h. Four adolescents had C24 h <40 ng/ml. All PK parameters were comparable with published data. All adolescents remained virologically suppressed at week 24. Significant decreases in fasting total cholesterol, triglyceride and low-density lipoprotein were observed (P-value <0.05). CONCLUSIONS: Virologically suppressed HIV-infected adolescents had adequate RPV exposure and remained virologically suppressed after switching from EFV. RPV can be used as long-term maintenance ART in HIV-infected adolescents. PMID- 28994662 TI - The dosimetric impact of including the patient table in CT dose estimates. AB - The purpose of this study was to evaluate the dosimetric impact of including the patient table in Monte Carlo CT dose estimates for both spiral scans and scan projection radiographs (SPR). CT scan acquisitions were simulated for a Siemens SOMATOM Force scanner (Siemens Healthineers, Forchheim, Germany) with and without a patient table present. An adult male, an adult female and a pediatric female voxelized phantom were simulated. The simulated scans included tube voltages of 80 and 120 kVp. Spiral scans simulated without a patient table resulted in effective doses that were overestimated by approximately 5% compared to the same simulations performed with the patient table present. Doses in selected individual organs (breast, colon, lung, red bone marrow and stomach) were overestimated by up to 8%. Effective doses from SPR acquired with the x-ray tube stationary at 6 o'clock (posterior-anterior) were overestimated by 14-23% when the patient table was not included, with individual organ dose discrepancies (breast, colon, lung red bone marrow and stomach) all exceeding 13%. The reference entrance skin dose to the back were in this situation overestimated by 6-15%. These results highlight the importance of including the patient table in patient dose estimates for such scan situations. PMID- 28994661 TI - Vitamin D supplementation decreases immune activation and exhaustion in HIV-1 infected youth. AB - BACKGROUND: Heightened immune activation and exhaustion drive HIV disease progression and comorbidities. Vitamin D has pleiotropic immunomodulatory effects, but little is known about the effects of supplementation in HIV. Our study investigates changes in immune activation and exhaustion markers after 12 months of supplementation in virologically suppressed HIV-infected youth with vitamin D insufficiency. METHODS: This is a randomized, active-control, double blind trial investigating with three different vitamin D3 doses (18,000 [standard/active-control dose], 60,000 [moderate dose] and 120,000 IU/month [high dose]) in 8-25-year-old HIV-infected youth on combination antiretroviral therapy with baseline serum 25-hydroxyvitamin D (25(OH)D) concentrations <=30 ng/ml. Only subjects (n=51) who maintained an undetectable HIV-1 RNA over the 12-month study period were included in this analysis. RESULTS: Baseline serum 25(OH)D concentrations and immune activation/exhaustion markers were not different between groups. By 12 months, 25(OH)D increased significantly within each dosing group with the greatest increase and most sustained concentrations >=30 ng/ml in the high-dose group. Overall, all measured markers decreased with CD4 activation (CD4+CD38+HLA-DR+), CD8 activation (CD8+CD38+HLA-DR+), CD4 exhaustion (CD4+CD38+HLA-DR+PD1+) and inflammatory monocytes (CD14+CD16+) reaching statistical significance. When analysed separately, there were no significant decreases in the moderate- or standard-dose groups, but CD4 and CD8 activation and inflammatory monocytes decreased significantly in the high-dose group. CONCLUSIONS: Vitamin D supplementation decreased markers of T-cell activation/exhaustion and monocyte activation in HIV-infected youth, with subjects given the highest dose (120,000 IU/month) showing the greatest decreases. These data suggest that high-dose vitamin D supplementation may attenuate immune activation and exhaustion, and serve as adjuvant therapy to antiretroviral therapy in HIV. ClinicalTrials.gov identifier: NCT01523496. PMID- 28994663 TI - System geometry optimization for molecular breast tomosynthesis with focusing multi-pinhole collimators. AB - Imaging of 99mTc-labelled tracers is gaining popularity for detecting breast tumours. Recently, we proposed a novel design for molecular breast tomosynthesis (MBT) based on two sliding focusing multi-pinhole collimators that scan a modestly compressed breast. Simulation studies indicate that MBT has the potential to improve the tumour-to-background contrast-to-noise ratio significantly over state-of-the-art planar molecular breast imaging. The aim of the present paper is to optimize the collimator-detector geometry of MBT. Using analytical models, we first optimized sensitivity at different fixed system resolutions (ranging from 5 to 12 mm) by tuning the pinhole diameters and the distance between breast and detector for a whole series of automatically generated multi-pinhole designs. We evaluated both MBT with a conventional continuous crystal detector with 3.2 mm intrinsic resolution and with a pixelated detector with 1.6 mm pixels. Subsequently, full system simulations of a breast phantom containing several lesions were performed for the optimized geometry at each system resolution for both types of detector. From these simulations, we found that tumour-to-background contrast-to-noise ratio was highest for systems in the 7 mm-10 mm system resolution range over which it hardly varied. No significant differences between the two detector types were found. PMID- 28994664 TI - Compton camera study for high efficiency SPECT and benchmark with Anger system. AB - Single photon emission computed tomography (SPECT) is at present one of the major techniques for non-invasive diagnostics in nuclear medicine. The clinical routine is mostly based on collimated cameras, originally proposed by Hal Anger. Due to the presence of mechanical collimation, detection efficiency and energy acceptance are limited and fixed by the system's geometrical features. In order to overcome these limitations, the application of Compton cameras for SPECT has been investigated for several years. In this study we compare a commercial SPECT Anger device, the General Electric HealthCare Infinia system with a High Energy General Purpose (HEGP) collimator, and the Compton camera prototype under development by the French collaboration CLaRyS, through Monte Carlo simulations (GATE-GEANT4 Application for Tomographic Emission-version 7.1 and GEANT4 version 9.6, respectively). Given the possible introduction of new radio-emitters at higher energies intrinsically allowed by the Compton camera detection principle, the two detectors are exposed to point-like sources at increasing primary gamma energies, from actual isotopes already suggested for nuclear medicine applications. The Compton camera prototype is first characterized for SPECT application by studying the main parameters affecting its imaging performance: detector energy resolution and random coincidence rate. The two detector performances are then compared in terms of radial event distribution, detection efficiency and final image, obtained by gamma transmission analysis for the Anger system, and with an iterative List Mode-Maximum Likelihood Expectation Maximization (LM-MLEM) algorithm for the Compton reconstruction. The results show for the Compton camera a detection efficiency increased by a factor larger than an order of magnitude with respect to the Anger camera, associated with an enhanced spatial resolution for energies beyond 500 keV. We discuss the advantages of Compton camera application for SPECT if compared to present commercial Anger systems, with particular focus on dose delivered to the patient, examination time, and spatial uncertainties. PMID- 28994666 TI - Primal-dual convex optimization in large deformation diffeomorphic metric mapping: LDDMM meets robust regularizers. AB - This paper proposes a method for primal-dual convex optimization in variational large deformation diffeomorphic metric mapping problems formulated with robust regularizers and robust image similarity metrics. The method is based on Chambolle and Pock primal-dual algorithm for solving general convex optimization problems. Diagonal preconditioning is used to ensure the convergence of the algorithm to the global minimum. We consider three robust regularizers liable to provide acceptable results in diffeomorphic registration: Huber, V-Huber and total generalized variation. The Huber norm is used in the image similarity term. The primal-dual equations are derived for the stationary and the non-stationary parameterizations of diffeomorphisms. The resulting algorithms have been implemented for running in the GPU using Cuda. For the most memory consuming methods, we have developed a multi-GPU implementation. The GPU implementations allowed us to perform an exhaustive evaluation study in NIREP and LPBA40 databases. The experiments showed that, for all the considered regularizers, the proposed method converges to diffeomorphic solutions while better preserving discontinuities at the boundaries of the objects compared to baseline diffeomorphic registration methods. In most cases, the evaluation showed a competitive performance for the robust regularizers, close to the performance of the baseline diffeomorphic registration methods. PMID- 28994665 TI - Combining deep learning with anatomical analysis for segmentation of the portal vein for liver SBRT planning. AB - Automated segmentation of the portal vein (PV) for liver radiotherapy planning is a challenging task due to potentially low vasculature contrast, complex PV anatomy and image artifacts originated from fiducial markers and vasculature stents. In this paper, we propose a novel framework for automated segmentation of the PV from computed tomography (CT) images. We apply convolutional neural networks (CNNs) to learn the consistent appearance patterns of the PV using a training set of CT images with reference annotations and then enhance the PV in previously unseen CT images. Markov random fields (MRFs) were further used to smooth the results of the enhancement of the CNN enhancement and remove isolated mis-segmented regions. Finally, CNN-MRF-based enhancement was augmented with PV centerline detection that relied on PV anatomical properties such as tubularity and branch composition. The framework was validated on a clinical database with 72 CT images of patients scheduled for liver stereotactic body radiation therapy. The obtained accuracy of the segmentation was [Formula: see text] 0.83 and [Formula: see text] 1.08 mm in terms of the median Dice coefficient and mean symmetric surface distance, respectively, when segmentation is encompassed into the PV region of interest. The obtained results indicate that CNNs and anatomical analysis can be used for the accurate segmentation of the PV and potentially integrated into liver radiation therapy planning. PMID- 28994667 TI - Relative contribution of different altered motor unit control to muscle weakness in stroke: a simulation study. AB - OBJECTIVE: Chronic muscle weakness impacts the majority of individuals after a stroke. The origins of this hemiparesis is multifaceted, and an altered spinal control of the motor unit (MU) pool can lead to muscle weakness. However, the relative contribution of different MU recruitment and discharge organization is not well understood. In this study, we sought to examine these different effects by utilizing a MU simulation with variations set to mimic the changes of MU control in stroke. APPROACH: Using a well-established model of the MU pool, this study quantified the changes in force output caused by changes in MU recruitment range and recruitment order, as well as MU firing rate organization at the population level. We additionally expanded the original model to include a fatigue component, which variably decreased the output force with increasing length of contraction. Differences in the force output at both the peak and fatigued time points across different excitation levels were quantified and compared across different sets of MU parameters. MAIN RESULTS: Across the different simulation parameters, we found that the main driving factor of the reduced force output was due to the compressed range of MU recruitment. Recruitment compression caused a decrease in total force across all excitation levels. Additionally, a compression of the range of MU firing rates also demonstrated a decrease in the force output mainly at the higher excitation levels. Lastly, changes to the recruitment order of MUs appeared to minimally impact the force output. SIGNIFICANCE: We found that altered control of MUs alone, as simulated in this study, can lead to a substantial reduction in muscle force generation in stroke survivors. These findings may provide valuable insight for both clinicians and researchers in prescribing and developing different types of therapies for the rehabilitation and restoration of lost strength after stroke. PMID- 28994668 TI - Correction of patient motion in cone-beam CT using 3D-2D registration. AB - Cone-beam CT (CBCT) is increasingly common in guidance of interventional procedures, but can be subject to artifacts arising from patient motion during fairly long (~5-60 s) scan times. We present a fiducial-free method to mitigate motion artifacts using 3D-2D image registration that simultaneously corrects residual errors in the intrinsic and extrinsic parameters of geometric calibration. The 3D-2D registration process registers each projection to a prior 3D image by maximizing gradient orientation using the covariance matrix adaptation-evolution strategy optimizer. The resulting rigid transforms are applied to the system projection matrices, and a 3D image is reconstructed via model-based iterative reconstruction. Phantom experiments were conducted using a Zeego robotic C-arm to image a head phantom undergoing 5-15 cm translations and 5 15 degrees rotations. To further test the algorithm, clinical images were acquired with a CBCT head scanner in which long scan times were susceptible to significant patient motion. CBCT images were reconstructed using a penalized likelihood objective function. For phantom studies the structural similarity (SSIM) between motion-free and motion-corrected images was >0.995, with significant improvement (p < 0.001) compared to the SSIM values of uncorrected images. Additionally, motion-corrected images exhibited a point-spread function with full-width at half maximum comparable to that of the motion-free reference image. Qualitative comparison of the motion-corrupted and motion-corrected clinical images demonstrated a significant improvement in image quality after motion correction. This indicates that the 3D-2D registration method could provide a useful approach to motion artifact correction under assumptions of local rigidity, as in the head, pelvis, and extremities. The method is highly parallelizable, and the automatic correction of residual geometric calibration errors provides added benefit that could be valuable in routine use. PMID- 28994670 TI - Atmospheric pollution in cardiac operating rooms. PMID- 28994671 TI - Congenital syndromes affecting heart and airway alike. PMID- 28994672 TI - Low-dose intravenous ketamine for postcardiac surgery pain: Effect on opioid consumption and the incidence of chronic pain. AB - BACKGROUND: Recent meta-analyses have concluded that low-dose intravenous ketamine infusions (LDKIs) during the postoperative period may help to decrease acute and chronic postoperative pain after major surgery. AIMS: This study aims to evaluate the level of pain at least 3 months after surgery for patients treated with a postoperative LDKI versus patients who were not treated with a postoperative LDKI. METHODS: Administrative and Ethics Board approval were obtained for this study. We performed a retrospective chart review for all patients receiving LDKI, and equal number of age-, sex-, and surgery-matched patients who did not receive LDKI. Low-dose ketamine was prepared using 100 mg of ketamine in 100 ml of normal saline and run between 50 and 200 mcg/kg/h. RESULTS: We reviewed 115 patients with LDKI and 115 without LDKI. The average age was 63.1 years, 73% of the patients were men and sex was evenly distributed between LDKI and non-LDKI. The average duration of the ketamine infusions was 26.8 h with the average dose being 169.9 mg. At an average of 9 months after surgery, 42% of the ketamine group and 38% of the nonketamine group stated that they had had pain on discharge. Of these patients, 30% of the ketamine group and 26% of the nonketamine group still had pain at the time of the phone call. Women in both groups had more acute and chronic pain than men. CONCLUSION: These results show that LDKI does not promote a decrease in long-term postoperative pain. PMID- 28994673 TI - An innovative technique to improve safety of volatile anesthetics suction from the cardiopulmonary bypass circuit. AB - CONTEXT: Myocardial injury during cardiac surgery on cardiopulmonary bypass (CPB) is a major determinant of morbidity and mortality. Preclinical and clinical evidence of dose- and time-related cardioprotective effects of volatile anesthetic drugs exist and their use during the whole surgery duration could improve perioperative cardiac protection. Even if administering volatile agents during CPB are relatively easy, technical problems, such as waste gas scavenging, may prevent safe and manageable administration of halogenated vapors during CPB. AIMS: The aim of this study is to improve the safe administration of volatile anesthesia during CPB. SETTINGS AND DESIGN: Tertiary teaching hospital. SUBJECTS AND METHODS: We describe an original device that collects and disposes of any volatile anesthetic vapors present in the exit stream of the oxygenator, hence preventing its dispersal into the operating theatre environment and adaptively regulates pressure of oxygenator chamber in the CPB circuit. RESULTS: We have so far applied a prototype of this device in more than 1300 adult cardiac surgery patients who received volatile anesthetics during the CPB phase. CONCLUSIONS: Widespread implementation of scavenging system like the one we designed may facilitate the perfusionist and the anesthesiologist in delivering these cardioprotective drugs with beneficial impact on patients' outcome without compromising on safety. PMID- 28994674 TI - Relationship between perioperative left atrial appendage doppler velocity estimates and new-onset atrial fibrillation in patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass. AB - BACKGROUND: Literature search reveals that postoperative atrial fibrillation (POAF) occurs in 15%-40% of coronary artery bypass graft (CABG) patients. Although several risk models exist for predicting the development of POAF, few have studied left atrial appendage (LAA) velocity. We hypothesize that an association between LAA velocity and development of POAF exists. DESIGN AND METHODS: Single institution university hospital prospective observational clinical study performed between May 2016 and November 2016 in 96 adult patients undergoing CABG surgery utilizing cardiopulmonary bypass (CPB). Transesophageal echocardiography was performed perioperatively to measure LAA velocity and left atrial (LA) size after anesthetic induction, post-CPB and during the postoperative period before extubation. Student's t-test was used for inter-group comparisons. Data are expressed as mean +/- (standard deviation). The value of P < 0.05 was considered statistically significant. RESULTS: A total of 95 patients (69 males and 26 females) completed the study and were included in the final analysis. Of these, 21 (22%) (15 males and 5 females) developed POAF. The patient group which developed POAF was compared with the group that did not develop POAF. On comparing mean age of patients in each group (59 years in patients with no POAF and 63.71 years in patients with POAF, P = 0.04). LA volume indexed in POAF group (34.13 ml/m2) compared with that in group with no POAF (34.82 ml/m2) resulted in P = 0.04. Mean LAA velocities (pre-CPB, post-CPB, postoperative Intensive Care Unit) in group with no POAF were 41.06, 56.33, and 60.44 cm/s, respectively, whereas in the other group with POAF the values were 39.68, 55.04, and 58.09 cm/s, respectively. No statistical significance was noted (P > 0.05). Comparison of comorbidities also did not yield any significant results (P > 0.05). CONCLUSIONS: Decreasing LAA velocity does not appear to independently predict the development of POAF in patients undergoing CABG surgery with the use of CPB. There is, however, a positive correlation of POAF with age and LA volume. PMID- 28994676 TI - Does bilevel positive airway pressure improve outcome of acute respiratory failure after open-heart surgery? AB - BACKGROUND: Respiratory failure is of concern in the postoperative period after cardiac surgeries. Invasive ventilation (intermittent positive pressure ventilation [IPPV]) carries the risks and complications of intubation and mechanical ventilation (MV). AIMS: Noninvasive positive pressure ventilation (NIPPV) is an alternative method and as effective as IPPV in treating insufficiency of respiration with less complications and minimal effects on respiratory and hemodynamic parameters next to open-heart surgery. DESIGN: This is a prospective, randomized and controlled study. MATERIALS AND METHODS: Forty four patients scheduled for cardiac surgery were divided into two equal groups: Group I (IPPV) and Group II (NIPPV). Heart rate (HR), mean arterial pressure (MAP), respiratory rate (RR), oxygen saturation (SpO2), arterial blood gas, weaning time, reintubation, tracheotomy rate, MV time, postoperative hospital stay, and ventilator-associated pneumonia during the period of hospital stay were recorded. RESULTS: There was statistically significant difference in HR between groups with higher in Group I at 30 and 60 min and at 12 and 24 h. According to MAP, it started to increase significantly at hypoxemia, 15 min, 30 min, 4 h, 12 h, and at 24 h which was higher in Group I also. RR, PaO2, and PaCO2showed significant higher in Group II at 15, 30, and 60 min and 4 h. According to pH, there was a significant difference between groups at 15, 30, and 60 min and at 4, 12, and 24 h postoperatively. SpO2showed higher significant values in Group I at 15 and 30 min and at 12 h postoperatively. Duration of postoperative supportive ventilation was higher in Group I than that of Group II with statistically significant difference. Complications were statistically insignificant between Group I and Group II. CONCLUSION: Our study showed superiority of invasive over noninvasive mode of ventilator support. However, NIPPV (bilevel positive airway pressure) was proved to be a safe method. PMID- 28994675 TI - Comparison of the renoprotective effect of dexmedetomidine and dopamine in high risk renal patients undergoing cardiac surgery: A double-blind randomized study. AB - OBJECTIVE: The purpose of the current study was to compare the renoprotective effects of continuous infusion of dexmedetomidine and dopamine in high-risk renal patients undergoing cardiac surgery. DESIGN: A double-blind randomized study. SETTING: Cardiac Centers. PATIENTS: One hundred and fifty patients with baseline serum creatinine level >=1.4 mg/dl were scheduled for cardiac surgery with cardiopulmonary bypass. INTERVENTION: The patients were classified into two groups (each = 75): Group Dex - the patients received a continuous infusion of dexmedetomidine 0.4 MUg/kg/h without loading dose during the procedure and the first 24 postoperative hours and Group Dopa - the patients received a continuous infusion of dopamine 3 MUg/kg/min during the procedure and the first 24 postoperative hours. MEASUREMENTS: The monitors included serum creatinine, creatinine clearance, blood urea nitrogen, and urine output. MAIN RESULTS: The creatinine levels and blood urea nitrogen decreased at days 1, 2, 3, 4, and 5 in Dex group and increased in patients of Dopa group (P < 0.05). The creatinine clearance increased at days 1, 2, 3, 4, and 5 in Dex group and decreased in patients of Dopa group (P < 0.05). The amount of urine output was too much higher in the Dex group than the Dopa group (P < 0.05). CONCLUSIONS: The continuous infusion of dexmedetomidine during cardiac surgery has a renoprotective effect and decreased the deterioration in the renal function in high-risk renal patients compared to the continuous infusion of dopamine. PMID- 28994677 TI - Comparison of dexmedetomidine and ketamine versus propofol and ketamine for procedural sedation in children undergoing minor cardiac procedures in cardiac catheterization laboratory. AB - BACKGROUND: The ideal anaesthetic technique for management of paediatric patients scheduled to undergo cardiac catheterisation is still not standardised. AIM: To compare the effects of ketamine-propofol and ketamine-dexmedetomidine combinations on hemodynamic parameters and recovery time in paediatric patients undergoing minor procedures and cardiac catheterisation under sedation for various congenital heart diseases. MATERIAL AND METHODS: 60 children of either sex undergoing cardiac catheterisation were randomly assigned into two groups Dexmedetomidine-ketamine group (DK) and Propofol-ketamine (PK) of 30 patients each. All patients were premedicated with glycopyrrolate and midazolam (0.05mg/kg) intravenously 5-10 min before anaesthetic induction. Group 'DK'received dexmedetomidineiv infusion 1 MUg/kg over 10 min + ketamine1mg/kg bolus, followed by iv infusion of dexmedetomidine 0.5MUg/kg/hr and of ketamine1 mg/kg/hr. Group 'PK' received propofol 1mg/kg and ketamine 1mg/kg/hr for induction followed by iv infusion of propofol 100 MUg/kg/hr and ketamine 1 mg/kg/hr for maintenance. Haemodynamic parameters and recovery time was recorded postoperatively. STATISTICAL ANALYSIS: Independent sample t test was used to compare the statistical significance of continuous variables of both the groups.Chi square test was used for numerical data like gender.Fischer exact test was applied for non parametric data like ketamine consumption. RESULTS: We observed that heart rate in dexmedetomidine (DK) group was significantly lower during the initial 25 mins after induction compared to the propofol (PK) group. Recovery was prolonged in the DK group compared to the PK group (40.88 vs. 22.28 min). Even ketamine boluses consumption was higher in DK group. CONCLUSION: Use of dexmedetomidine-ketamine combination is a safe alternative, without any hemodynamic orrespiratory effects during the cardiac catheterization procedure but with some delayed recovery. PMID- 28994678 TI - Evaluation of the effect of metformin and insulin in hyperglycemia treatment after coronary artery bypass surgery in nondiabetic patients. AB - INTRODUCTION: Insulin therapy is the most commonly used treatment for controlling hyperglycemia after coronary artery bypass surgery in both diabetic and nondiabetic patients. Metformin has been indicated for critically ill patients as an alternate for the treatment of hyperglycemia. This study evaluated the effect of metformin and insulin in hyperglycemia treatment after coronary artery bypass surgery in nondiabetic patients. SETTINGS AND DESIGN: This study was a clinical trial comprising nondiabetic patients who had undergone coronary artery bypass surgery. Patients were randomly divided into the insulin group and the metformin group. METHODS: Patients in the insulin group received continuous infusion of insulin while those in the metformin group received 500 mg metformin tablets twice daily. All the patients were followed up for 3 days after stabilization of blood glucose levels. STATISTICAL ANALYSIS: Data were analyzed using Chi-square test and Mann-Whitney U-test. RESULTS: This study included a total of 56 patients. During the study period, the mean blood glucose levels decreased from 225.24 to 112.36 mg/dl (?112.88 mg/dl) in the insulin group and from 221.80 to 121.92 mg/dl in the metformin group (?99.88 mg/dl). There was no significant difference in the blood glucose levels of the patients between the two groups at any measurement times (P > 0.05). CONCLUSION: Using 500 mg metformin twice daily is similar to using insulin in nondiabetic patients undergoing coronary artery bypass graft. Therefore, the use of metformin can be considered as a treatment strategy for controlling hyperglycemia in this group of patients. PMID- 28994679 TI - Ischemic mitral regurgitation. AB - Ischemic mitral regurgitation (IMR) is a frequent complication of left ventricular (LV) global or regional pathological remodeling due to chronic coronary artery disease. It is not a valve disease but represents the valvular consequences of increased tethering forces and reduced closing forces. IMR is defined as mitral regurgitation caused by chronic changes of LV structure and function due to ischemic heart disease and it worsens the prognosis. In this review, we discuss on etiology, pathophysiology, and mechanisms of IMR, its classification, evaluation, and therapeutic corrective methods of IMR. PMID- 28994680 TI - Rising Central venous pressure: Impending right-sided failure? AB - Central venous pressure generally indicates right sided cardiac filling pressure. Although it is a static hemodynamic parameter, however trend of CVP gives important information regarding the patient's management. Patient with left ventricular assist device is prone to develop right ventricular dysfunction which can easily be suspected by trend of CVP. However rising CVP does not always imply right heart dysfunction. PMID- 28994681 TI - Pulmonary valve reconstruction during conduit revision: Technique and transesophageal echocardiography imaging. AB - Transesophageal echocardiography can be a useful adjunct in assessing the quality of repair in patients undergoing novel methods of reconstruction of the right ventricular outflow. We present one such patient here. PMID- 28994682 TI - Successful surgical osteoplasty of the left main coronary artery with concomitant mitral valve replacement and tricuspid annuloplasty. AB - A 50-year-old woman with rheumatic heart disease, mitral stenosis, and critical isolated left main ostial stenosis was successfully treated by mitral valve replacement, tricuspid annuloplasty, and surgery of left main osteoplasty and is reported for its rarity. Notable clinical findings included an intermittently irregular pulse, blood pressure of 100/70 mmHg, cardiomegaly, a diastolic precordial thrill, a mid-diastolic murmur without presystolic accentuation that was loudest at the mitral area. Chest radiograph revealed cardiomegaly with a cardiothoracic ratio of 0.7 due to enlarged right atrium, right ventricle with a straightened left heart border and evidence of pulmonary hypertension. The investigation shows that surgical reconstruction of the left main coronary artery is safe and effective for the treatment. PMID- 28994683 TI - Sutureless aortic valve implantation in patient with porcelain aorta via unclamped aorta and deep hypothermic circulatory arrest. AB - Severe atherosclerotic calcification of the ascending aorta, the so-called porcelain aorta, precludes cardiac surgeons from placing an aortic cross-clamp and direct aortic cannulation due to the increased risk of systemic embolism and stroke. In the present report, we support the option of sutureless valve implantation in a case of a porcelain ascending aorta, with deep hypothermic circulatory arrest and also without aortic cross-clamp. PMID- 28994684 TI - Atrial myxomas causing severe left and right ventricular dysfunction. AB - Myxomas are the most common cardiac tumors, accounting for about 50% of benign primary cardiac tumors, with the majority located in the left atrium, and 80% of which originate in the interatrial septum. We report two cases with severe cachexia, neurological sequelae, and severe biventricle dysfunction secondary to atrial myxomas with marked early improvement after tumor excision. PMID- 28994685 TI - Rhabdomyolysis and compartment syndrome in a bodybuilder undergoing minimally invasive cardiac surgery. AB - Rhabdomyolysis is the result of skeletal muscle tissue injury and is characterized by elevated creatine kinase levels, muscle pain, and myoglobinuria. It is caused by crush injuries, hyperthermia, drugs, toxins, and abnormal metabolic states. This is often difficult to diagnose perioperatively and can result in renal failure and compartment syndrome if not promptly treated. We report a rare case of inadvertent rhabdomyolysis and compartment syndrome in a bodybuilder undergoing minimally invasive cardiac surgery. The presentation, differential diagnoses, and management are discussed. Hyperkalemia may be the first presenting sign. Early recognition and management are essential to prevent life-threatening complications. PMID- 28994686 TI - Lutembacher syndrome: Dilemma of doing a tricuspid annuloplasty. AB - We discuss the case of a 24-year-old woman with Lutembacher syndrome and severe tricuspid regurgitation (TR) who underwent surgical closure of atrial septal defect and mitral valve replacement without tricuspid annuloplasty despite a severe TR and a large tricuspid annulus on preoperative echo. The pathophysiology of Lutembacher syndrome is discussed below. The utility of perioperative echocardiography in assessing the annular diameter, tenting area and coaptation depth and thus providing insights into the functioning of the tricuspid valve will also be emphasized. PMID- 28994687 TI - Two episodes of cardiac tamponade in the same patient from removing pacing wires and a pericardial drain: A case report. AB - A patient presented for an elective transcatheter aortic valve replacement with temporary transvenous pacing (TVP) wires placement per protocol. On postoperative day 1, the patient remained stable, so the wires were subsequently removed, after which the patient acutely decompensated, with transthoracic echocardiography revealing pericardial effusion. Emergent pericardiocentesis was performed, and a pericardial drain was placed. Three days later, the drain was removed; again, the patient acutely decompensated, requiring another emergent pericardiocentesis. Despite the relatively benign nature of TVP wires and pericardial drains, the possibility of cardiac tamponade should be kept in mind as a potential complication when they are being removed. PMID- 28994688 TI - The use of intravenous hydroxocobalamin as a rescue in methylene blue-resistant vasoplegic syndrome in cardiac surgery. AB - Vasoplegic syndrome is a well-recognized complication during cardiopulmonary bypass (CPB) and is associated with increased morbidity and mortality, especially when refractory to conventional vasoconstrictor therapy. This is the first reported case of vasoplegia on CPB unresponsive to methylene blue whereas responsive to hydroxocobalamin, which indicates that the effect of hydroxocobalamin outside of the nitric oxide system is significant or that the two drugs have a synergistic effect in one or multiple mechanisms. PMID- 28994689 TI - A case report of combined radical pericardiectomy and beating heart coronary artery bypass grafting in a patient with tubercular chronic constrictive pericarditis with coronary artery disease. AB - We here report a successful midterm outcome following combined off-pump radical pericardiectomy and coronary artery bypass surgery (CABG) in a 65-year-old male patient who was suffering from chronic constrictive calcified tubercular pericarditis with coronary artery disease. Simultaneous off-pump CABG and radical pericardiectomy for nonsurgical constrictive pericarditis is reported very rarely in English literature. PMID- 28994690 TI - Perioperative management of a patient with glanzmann's thrombasthenia for mitral valve repair under cardiopulmonary bypass. AB - A 30-year-old male patient presented with Glanzmann's thrombasthenia and mitral valve prolapse. He was in acute decompensated congestive heart failure due to severe mitral and tricuspid regurgitation. After his cardiac failure had been stabilized, the patient was subjected to mitral and tricuspid valve repair. His transfusion requirements were guided by thrombelastography and his bleeding disorder was managed by infusing single donor plasmapheresed platelet transfusions in the perioperative period. The patient underwent surgery uneventfully. PMID- 28994691 TI - Distortion of aortic valve from mechanical traction imposed by the mitral valve prosthesis: The three-dimensional transesophageal echocardiographic perception. AB - Iatrogenic injury to the aortic valve is a rare but frequently reported complication during mitral valve surgeries. Intraoperative 2-dimensional transesophageal echocardiography (2D TEE) has a major impact in diagnosing these injuries, so that timely intervention is possible. However, 2D TEE has lot of limitations during the perioperative period, which can be overcome by the three dimensional echocardiography (3D-TEE). We report a case where 3D TEE has undoubtedly delineated the cause for distortion of aortic sinus after mitral valve replacement and helped in the successful outcome. PMID- 28994692 TI - Think beyond right bundle branch block in atrial septal defect. PMID- 28994693 TI - Accidental placement of central venous catheter into internal mammary vein: A rare catheter malposition. PMID- 28994694 TI - Bifid epiglottis: What perioperative physician should know about it? PMID- 28994695 TI - Inadvertent diversion of inferior vena cava to left atrium after repair of atrial septal defect - Early diagnosis and correction of error: role of intraoperative transesophageal echocardiography. PMID- 28994696 TI - An uncommon intraoperative implantable cardiac device complication and subsequent troubleshooting. PMID- 28994697 TI - Hypertrophic obstructive cardiomyopathy, yamaguchi syndrome and kounis syndrome: Clinical challenges. PMID- 28994698 TI - Priority of a Hesitant Fuzzy Linguistic Preference Relation with a Normal Distribution in Meteorological Disaster Risk Assessment. AB - As meteorological disaster systems are large complex systems, disaster reduction programs must be based on risk analysis. Consequently, judgment by an expert based on his or her experience (also known as qualitative evaluation) is an important link in meteorological disaster risk assessment. In some complex and non-procedural meteorological disaster risk assessments, a hesitant fuzzy linguistic preference relation (HFLPR) is often used to deal with a situation in which experts may be hesitant while providing preference information of a pairwise comparison of alternatives, that is, the degree of preference of one alternative over another. This study explores hesitation from the perspective of statistical distributions, and obtains an optimal ranking of an HFLPR based on chance-restricted programming, which provides a new approach for hesitant fuzzy optimisation of decision-making in meteorological disaster risk assessments. PMID- 28994699 TI - Fisetin Regulates Nrf2 Expression and the Inflammation-Related Signaling Pathway to Prevent UVB-Induced Skin Damage in Hairless Mice. AB - Chronic ultraviolet (UV) exposure may cause skin damage, disrupt skin barrier function, and promote wrinkle formation. UV induces oxidative stress and inflammation, which results in extracellular matrix degradation in the dermis and epidermal hyperplasia. Our previous study demonstrated that fisetin exerts photoprotective activity by inhibiting mitogen-activated protein kinase/activator protein-1/matrix metalloproteinases (MMPs) activation. In this study, fisetin was applied topically to investigate its antiphotodamage effects in hairless mice. The erythema index (a* values) and transepidermal water loss were evaluated to assess skin damage, and immunohistochemical staining was conducted to elucidate the photoprotective mechanism of fisetin. The results revealed that the topical application of fisetin reduced UVB-induced increase in the a* value and wrinkle formation. In addition, fisetin inhibited epidermal hyperplasia and increased the collagen content in the dermis. Fisetin exerted photoprotective activity by inhibiting the expression of MMP-1, MMP-2, and cyclooxygenase-2 and increasing the expression of nuclear factor erythroid 2-related factor. Furthermore, fisetin increased the expression of filaggrin to prevent UVB-induced barrier function disruption. Altogether, the present results provide evidence of the effects and mechanisms of fisetin's antiphotodamage and antiphotoinflammation activities. PMID- 28994700 TI - Social Hazards as Manifested Workplace Discrimination and Health (Vietnamese and Ukrainian Female and Male Migrants in Czechia). AB - Social hazards as one of the dimensions of workplace discrimination are a potential social determinant of health inequalities. The aim of this study was to investigate relations between self-reported health and social hazard characteristics (defined as-discrimination as such, violence or threat of violence, time pressure or work overload and risk of accident) among Vietnamese and Ukrainian migrants (males and females) in Czechia by age, education level and marital status. This study is based on data from a survey of 669 immigrants in Czechia in 2013. Logistic regression analysis indicates that the given independent variables (given social hazards and socio-demographic characteristics), as predictors of a quality of self-reported health are more important for immigrant females than for males, irrespective of citizenship, albeit only for some of them and to differing extents. We found out that being exposed to the selected social hazards in the workplace leads to worsening self rated health, especially for females. On the other hand, there was no statistically significant relationship found between poor self-rated health and discrimination as such. Reality calls for more research and, consequently, better policies and practices in the field of health inequalities. PMID- 28994701 TI - Study of Statin- and Loratadine-Induced Muscle Pain Mechanisms Using Human Skeletal Muscle Cells. AB - Many drugs can cause unexpected muscle disorders, often necessitating the cessation of an effective medication. Inhibition of monocarboxylate transporters (MCTs) may potentially lead to perturbation of l-lactic acid homeostasis and muscular toxicity. Previous studies have shown that statins and loratadine have the potential to inhibit l-lactic acid efflux by MCTs (MCT1 and 4). The main objective of this study was to confirm the inhibitory potentials of atorvastatin, simvastatin (acid and lactone forms), rosuvastatin, and loratadine on l-lactic acid transport using primary human skeletal muscle cells (SkMC). Loratadine (IC50 31 and 15 uM) and atorvastatin (IC50 ~130 and 210 uM) demonstrated the greatest potency for inhibition of l-lactic acid efflux at pH 7.0 and 7.4, respectively (~2.5-fold l-lactic acid intracellular accumulation). Simvastatin acid exhibited weak inhibitory potency on l-lactic acid efflux with an intracellular lactic acid increase of 25-35%. No l-lactic acid efflux inhibition was observed for simvastatin lactone or rosuvastatin. Pretreatment studies showed no change in inhibitory potential and did not affect lactic acid transport for all tested drugs. In conclusion, we have demonstrated that loratadine and atorvastatin can inhibit the efflux transport of l-lactic acid in SkMC. Inhibition of l-lactic acid efflux may cause an accumulation of intracellular l-lactic acid leading to the reported drug-induced myotoxicity. PMID- 28994703 TI - A Straight Skeleton Based Connectivity Restoration Strategy in the Presence of Obstacles for WSNs. AB - Connectivity has significance in both of data collection and aggregation for Wireless Sensor Networks (WSNs). Once the connectivity is lost, relay nodes are deployed to build a Steiner Minimal Tree (SMT) such that the inter-component connection is reestablished. In recent years, there has been a growing interest in connectivity restoration problems. In previous works, the deployment area of a WSN is assumed to be flat without obstacles. However, such an assumption is not realistic. In addition, most of the existing strategies chose the representative of each component, which serves as the starting point of relay node deployment during the connectivity restoration, either in a random way or in the shortest distance based manner. In fact, both ways of representative selection could potentially increase the length of the SMT such that more relay nodes are required. In this paper, a novel connectivity restoration strategy is proposed Obstacle-Avoid connectivity restoration strategy based on Straight Skeletons (OASS), which employs both the polygon based representative selection with the presence of obstacles and the straight skeleton based SMT establishment. The OASS is proved to be a 3- o p t approximation algorithm with the complexity of O ( n log n ) , and the approximation ratio can reduce to 3 3 2 while it satisfies a certain condition. The theoretical analysis and simulations show that the performance of the OASS is better than other strategies in terms of the relay count and the quality of the established topology (i.e., distances between components, delivery latency and balanced traffic load) as well. PMID- 28994702 TI - Transforming Growth Factor-beta Drives the Transendothelial Migration of Hepatocellular Carcinoma Cells. AB - The entry of malignant hepatocytes into blood vessels is a key step in the dissemination and metastasis of hepatocellular carcinoma (HCC). The identification of molecular mechanisms involved in the transmigration of malignant hepatocytes through the endothelial barrier is of high relevance for therapeutic intervention and metastasis prevention. In this study, we employed a model of hepatocellular transmigration that mimics vascular invasion using hepatic sinusoidal endothelial cells and malignant hepatocytes evincing a mesenchymal-like, invasive phenotype by transforming growth factor (TGF)-beta. Labelling of respective cell populations with various stable isotopes and subsequent mass spectrometry analyses allowed the "real-time" detection of molecular changes in both transmigrating hepatocytes and endothelial cells. Interestingly, the proteome profiling revealed 36 and 559 regulated proteins in hepatocytes and endothelial cells, respectively, indicating significant changes during active transmigration that mostly depends on cell-cell interaction rather than on TGF-beta alone. Importantly, matching these in vitro findings with HCC patient data revealed a panel of common molecular alterations including peroxiredoxin-3, epoxide hydrolase, transgelin-2 and collectin 12 that are clinically relevant for the patient's survival. We conclude that hepatocellular plasticity induced by TGF-beta is crucially involved in blood vessel invasion of HCC cells. PMID- 28994704 TI - Characterization of Mucosal Disaccharidases from Human Intestine. AB - In this study, we used a brush border membrane (BBM) preparation from human small intestine to analyze the proportion and the activity of major intestinal disaccharidases, including sucrase-isomaltase (SI), maltase-glucoamylase (MGAM) and lactase-phlorizin hydrolase (LPH). SI, MGAM and LPH respectively constituted 8.2%, 2.7% and 1.4% of total BBM protein. The activity of SI and LPH decreased threefold after purification from the brush border membrane, which highlights the effect of membrane microdomains on the functional capacity of these enzymes. All of the disaccharidases showed optimal activity at pH 6, over 50% residual activity between pH 5 to pH 7, and increasing activity with rising temperatures up to 45 degrees C, along with a stable functional structure. Therefore the enzymes can withstand mild intraluminal pH alterations with adequate function, and are able to increase their activity with elevated core body temperature. Our data provide a functional measure for characterization of intestinal disaccharidases under different physiological and pathological conditions. PMID- 28994706 TI - Analysis of the Impact of Known SPINK1 Missense Variants on Pre-mRNA Splicing and/or mRNA Stability in a Full-Length Gene Assay. AB - It is increasingly appreciated that missense variants may not only alter protein structure and function but may also influence pre-mRNA splicing and/or mRNA stability. Here we explore this issue in the context of currently known SPINK1 missense variants using a full-length gene assay. We demonstrated that 4 (17%) out of 24 variants tested significantly reduced pre-mRNA splicing and/or stability as compared with the wild-type. However, since the strongest effect observed was a 23% reduction from normal, the contribution of SPINK1 missense variants to the clinical phenotype through an impact on mRNA processing alone may be relatively minor compared with their effects in relation to protein structure/function. PMID- 28994705 TI - Role of Purified Anthocyanins in Improving Cardiometabolic Risk Factors in Chinese Men and Women with Prediabetes or Early Untreated Diabetes-A Randomized Controlled Trial. AB - Objective: In vitro and animal studies suggest that purified anthocyanins have favorable effects on metabolic profiles, but clinical trials have reported inconsistent findings. Furthermore, no study has been specifically conducted among individuals with prediabetes. The aim of this study was to investigate whether purified anthocyanins could improve cardiometabolic risk factors in Chinese adults with early untreated hyperglycemia. Research Design and Methods: This was a 12-week randomized, double-blind, placebo-controlled trial. A total of 160 participants aged 40-75 years with prediabetes or early untreated diabetes were randomly allocated to receive either purified anthocyanins (320 mg/day, n = 80) or placebo (n = 80) of identical appearance. A three-hour oral glucose tolerance test (OGTT) was performed, and cardiometabolic biomarkers (glycated hemoglobin A1c (HbA1c), fasting and postprandial glucose, insulin, C-peptide, and lipids) were measured at baseline and at the end of the trial. Results: A total of 138 subjects completed the protocol. Compared with placebo, purified anthocyanins moderately reduced HbA1c (-0.14%, 95% CI: -0.23~-0.04%; p = 0.005), low-density lipoprotein-c (LDL-c) (-0.2 mmol/L, 95% CI: -0.38~-0.01, p = 0.04), apolipoprotein A-1 (apo A1) (0.09 g/L, 95% CI: 0.02~0.17; p = 0.02), and apolipoprotein B (apo B) (-0.07 g/L, 95% CI: -0.13~-0.01; p = 0.01) according to intention-to-treat analysis. Subgroup analyses suggested that purified anthocyanins were more effective at improving glycemic control, insulin sensitivity, and lipids among patients with elevated metabolic markers. Conclusions: The 12-week randomized controlled trials (RCT) in Chinese adults with prediabetes or early untreated diabetes indicated that purified anthocyanins favorably affected glycemic control and lipid profile. Future studies of a longer duration that explore the dose-response relationship among patients with cardiometabolic disorders are needed to confirm our findings. PMID- 28994708 TI - Photocatalytic Performance of a Novel MOF/BiFeO3 Composite. AB - In this study, MOF/BiFeO3 composite (MOF, metal-organic framework) has been synthesized successfully through a one-pot hydrothermal method. The MOF/BiFeO3 composite samples, pure MOF samples and BiFeO3 samples were characterized by X ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), and by UV-vis spectrophotometry. The results and analysis reveal that MOF/BiFeO3 composite has better photocatalytic behavior for methylene blue (MB) compared to pure MOF and pure BiFeO3. The enhancement of photocatalytic performance should be due to the introduction of MOF change the surface morphology of BiFeO3, which will increase the contact area with MB. This composing strategy of MOF/BiFeO3 composite may bring new insight into the designing of highly efficient photocatalysts. PMID- 28994709 TI - Advanced Materials in Polymer Electrolyte Fuel Cells. AB - Polymer electrolyte fuel cells (PEFCs) have attracted much interest due to the need for an efficient, non-polluting power source with high energy density for vehicles in urban environments, as well as portable electronics [...]. PMID- 28994707 TI - Why Human Papillomavirus Acute Infections Matter. AB - Most infections by human papillomaviruses (HPVs) are 'acute', that is non persistent. Yet, for HPVs, as for many other oncoviruses, there is a striking gap between our detailed understanding of chronic infections and our limited data on the early stages of infection. Here we argue that studying HPV acute infections is necessary and timely. Focusing on early interactions will help explain why certain infections are cleared while others become chronic or latent. From a molecular perspective, descriptions of immune effectors and pro-inflammatory pathways during the initial stages of infections have the potential to lead to novel treatments or to improved handling algorithms. From a dynamical perspective, adopting concepts from spatial ecology, such as meta-populations or meta-communities, can help explain why HPV acute infections sometimes last for years. Furthermore, cervical cancer screening and vaccines impose novel iatrogenic pressures on HPVs, implying that anticipating any viral evolutionary response remains essential. Finally, hints at the associations between HPV acute infections and fertility deserve further investigation given their high, worldwide prevalence. Overall, understanding asymptomatic and benign infections may be instrumental in reducing HPV virulence. PMID- 28994710 TI - Large-Scale Oral Treatment Study with the Four Most Promising D3-Derivatives for the Treatment of Alzheimer's Disease. AB - Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is associated with the aggregation of the amyloid beta protein (Abeta). Abeta oligomers are currently thought to be the major neurotoxic agent responsible for disease development and progression. Thus, their elimination is highly desirable for therapy development. Our therapeutic approach aims at specific and direct elimination of toxic Abeta oligomers by stabilizing Abeta monomers in an aggregation-incompetent conformation. We have proven that our lead compound "D3", an all d-enantiomeric-peptide, specifically eliminates Abeta oligomers in vitro. In vivo, D3 enhances cognition and reduces plaque load in several transgenic AD mouse models. Here, we performed a large-scale oral proof of concept efficacy study, in which we directly compared four of the most promising D3-derivatives in transgenic mice expressing human amyloid precursor protein with Swedish and London mutations (APPSL), transgenic mice, to identify the most effective compound. RD2 and D3D3, both derived from D3 by rational design, were discovered to be the most effective derivatives in improving cognition in the Morris water maze. The performance of RD2- and D3D3-treated mice within the Morris water maze was significantly better than placebo-treated mice and, importantly, nearly as good as those of non-transgenic littermates, suggesting a complete reversal of the cognitive deficit of APPSL mice. PMID- 28994711 TI - Production of Fish Protein Hydrolysates from Scyliorhinus canicula Discards with Antihypertensive and Antioxidant Activities by Enzymatic Hydrolysis and Mathematical Optimization Using Response Surface Methodology. AB - Fish discards are of major concern in new EU policies. Alternatives for the management of the new biomass that has to be landed is compulsory. The production of bioactive compounds from fish protein hydrolysates (FPH) has been explored in recent years. However, the viability of Scyliorhinus canicula discards, which might account for up to 90-100% of captures in mixed trawler, gillnet, and longline industrial fisheries, to produce FPH from the muscle with bioactivities has still not been studied in terms of the optimization of the experimental conditions to enhance its production. The effect of pH and temperature on the hydrolysis of the S.canicula muscle was mediated by three commercial proteases using response surface methodology. Temperatures of 64.6 degrees C and 60.8 degrees C and pHs of 9.40 and 8.90 were established as the best hydrolysis conditions for Alcalase and Esperase, respectively. Optimization of the best conditions for the maximization of antihypertensive and antioxidant activities was performed. Higher Angiotensin-converting enzyme (ACE) activity was found with Esperase. The pH optimum and temperature optimum for antioxidants were 55 degrees C/pH8.0 for ABTS/DPPH-Esperase, 63.1 degrees C/pH9.0 for DPPH-Alcalase, and 55 degrees C/pH9.0 for ABTS-Alcalase. No hydrolysis was detected when using Protamex. PMID- 28994712 TI - Improving Influenza Vaccination Rate among Primary Healthcare Workers in Qatar. AB - The purpose of this study was to improve influenza vaccination, and determine factors influencing vaccine declination among health care workers (HCW) in Qatar. We launched an influenza vaccination campaign to vaccinate around 4700 HCW in 22 Primary Health Care Corporation (PHCC) centers in Qatar between 1st and 15th of November, 2015. Our target was to vaccinate 60% of all HCW. Vaccine was offered free of charge at all centers, and information about the campaign and the importance of influenza vaccination was provided to employees through direct communication, emails, and social media networks. Staff were reported as vaccinated or non-vaccinated using a declination form that included their occupation, place of work and reasons for declining the vaccine. Survey responses were summarized as proportional outcomes. We exceeded our goal, and vaccinated 77% of the target population. Only 9% declined to take the vaccine, and the remaining 14% were either on leave or had already been vaccinated. Vaccine uptake was highest among aides (98.1%), followed by technicians (95.2%), and was lowest amongst pharmacists (73.2%), preceded by physicians (84%). Of those that declined the vaccine, 34% provided no reason, 18% declined it due to behavioral issues, and 21% declined it due to medical reasons. Uptake of influenza vaccine significantly increased during the 2015 immunization campaign. This is attributed to good planning, preparation, a high level of communication, and providing awareness and training to HCW with proper supervision and monitoring. PMID- 28994713 TI - The Luteovirus P4 Movement Protein Is a Suppressor of Systemic RNA Silencing. AB - The plant viral family Luteoviridae is divided into three genera: Luteovirus, Polerovirus and Enamovirus. Without assistance from another virus, members of the family are confined to the cells of the host plant's vascular system. The first open reading frame (ORF) of poleroviruses and enamoviruses encodes P0 proteins which act as silencing suppressor proteins (VSRs) against the plant's viral defense-mediating RNA silencing machinery. Luteoviruses, such as barley yellow dwarf virus-PAV (BYDV-PAV), however, have no P0 to carry out the VSR role, so we investigated whether other proteins or RNAs encoded by BYDV-PAV confer protection against the plant's silencing machinery. Deep-sequencing of small RNAs from plants infected with BYDV-PAV revealed that the virus is subjected to RNA silencing in the phloem tissues and there was no evidence of protection afforded by a possible decoy effect of the highly abundant subgenomic RNA3. However, analysis of VSR activity among the BYDV-PAV ORFs revealed systemic silencing suppression by the P4 movement protein, and a similar, but weaker, activity by P6. The closely related BYDV-PAS P4, but not the polerovirus potato leafroll virus P4, also displayed systemic VSR activity. Both luteovirus and the polerovirus P4 proteins also showed transient, weak local silencing suppression. This suggests that systemic silencing suppression is the principal mechanism by which the luteoviruses BYDV-PAV and BYDV-PAS minimize the effects of the plant's anti-viral defense. PMID- 28994714 TI - Inhibition of 5alpha-Reductase, IL-6 Secretion, and Oxidation Process of Equisetum debile Roxb. ex Vaucher Extract as Functional Food and Nutraceuticals Ingredients. AB - This study aims to investigate the biological activities related to hair loss of Equisetum debile extracts, including 5alpha-reductase inhibition, interleukin-6 (IL-6) secretion reduction, and anti-oxidation. E. debile extracts were obtained by maceration in various solvents. Crude extract (CE) was obtained by maceration in 95% ethanol. Chlorophyll-free extract (CF) was the CE which of the chlorophyll has been removed by electrocoagulation. Hexane extract (HE), ethyl acetate extract (EA), and ethanolic extract (ET) were fraction extracts obtained from maceration in hexane, ethyl acetate, and 95% ethanol, respectively. The extracts were investigated for inhibitory activity against 5alpha-reductase and IL-6 secretion. Total phenolic contents (TPC) were investigated and antioxidant activities were determined by means of 2,2'-azino-bis-3-ethylbenzothiazoline-6 sulfonic acid (ABTS), 2,2'-diphenyl-1-picrylhydrazyl (DPPH), and ferric reducing antioxidant power (FRAP) assays. The inhibition of lipid peroxidation was determined by the ferric thiocyanate method. The cytotoxicity of the extracts on dermal papilla cells and irritation test by hen's egg test chorioallantoic membrane assay were also investigated. All extracts could inhibit 5alpha reductase and decrease IL-6 secretion in lipopolysaccharide-stimulated macrophage. The antioxidant activity of E. debile extracts was directly related to their TPC. ET which contained the highest TPC (68.8 +/- 6.7 mg GA/g) showed the highest equivalent concentration (EC1) of 289.1 +/- 26.4 mM FeSO4/g, TEAC of 156.6 +/- 34.6 mM Trolox/g, and 20.0 +/- 6.0% DPPH inhibition. However, EA exhibited the highest inhibition against lipid peroxidation (57.2 +/- 0.4%). In addition, EA showed no cytotoxicity on dermal papilla cell line and no irritation on chorioallantoic membrane of hen's eggs. In conclusion, EA was suggested as the most attractive ingredients for functional food and nutraceuticals because of the high inhibitory activity against 5alpha-reductase, IL-6 secretion, and lipid peroxidation inhibition. PMID- 28994717 TI - Sparse Aperture InISAR Imaging via Sequential Multiple Sparse Bayesian Learning. AB - Interferometric inverse synthetic aperture radar (InISAR) imaging for sparse aperture (SA) data is still a challenge, because the similarity and matched degree between ISAR images from different channels are destroyed by the SA data. To deal with this problem, this paper proposes a novel SA-InISAR imaging method, which jointly reconstructs 2-dimensional (2-D) ISAR images from different channels through multiple response sparse Bayesian learning (M-SBL), a modification of sparse Bayesian learning (SBL), to achieve sparse recovery for multiple measurement vectors (MMV). We note that M-SBL suffers a heavy computational burden because it involves large matrix inversion. A computationally efficient M-SBL is proposed, which, proceeding in a sequential manner to avoid the time-consuming large matrix inversion, is denoted as sequential multiple sparse Bayesian learning (SM-SBL). Thereafter, SM-SBL is introduced to InISAR imaging to simultaneously reconstruct the ISAR images from different channels. Numerous experimental results validate that the proposed SM SBL-based InISAR imaging algorithm performs superiorly against the traditional single-channel sparse-signal recovery (SSR)-based InISAR imaging methods in terms of noise suppression, outlier reduction and 3-dimensional (3-D) geometry estimation. PMID- 28994716 TI - Association of Waist Circumference Gain and Incident Prediabetes Defined by Fasting Glucose: A Seven-Year Longitudinal Study in Beijing, China. AB - The risk of incident prediabetes with gain in waist circumference (WC) has not been addressed among Chinese adults. A total of 7951 participants who underwent health check-ups at the Beijing Physical Examination Center and Beijing Xiaotangshan hospital were recruited in 2009 and followed up in 2016. Participants were classified into four groups according to categories of percent WC gain: <=-2.5%, -2.5-2.5%, 2.5-5%, and >5%. The effect of WC gain on prediabetes was evaluated using modified Poisson regression models. Over seven years of follow-up, we identified 1034 prediabetes cases (413 women). Compared with a WC gain of <=-2.5%, participants with a WC gain of >5% have a higher risk of prediabetes, be they male (non-abdominal obesity at baseline group: RR = 1.57, 95% CI: 1.10-2.24, abdominal obesity at baseline group: RR = 1.66, 95% CI: 1.20 2.30) or female (non-abdominal obesity at baseline group: RR = 1.74, 95% CI: 1.14 2.64, abdominal obesity at baseline group: RR = 2.47, 95% CI: 1.43-4.28). In conclusion, the risk of prediabetes increased significantly with increasing WC for both genders in the Chinese population. Lifestyle interventions aiming at preventing abdominal obesity are urgently needed to reduce the increasing burden of prediabetes, diabetes, and its complications. PMID- 28994718 TI - Efficient Usage of Dense GNSS Networks in Central Europe for the Visualization and Investigation of Ionospheric TEC Variations. AB - The technique of the orthogonal projection of ionosphere electronic content variations for mapping total electron content (TEC) allows us to visualize ionospheric irregularities. For the reconstruction of global ionospheric characteristics, numerous global navigation satellite system (GNSS) receivers located in different regions of the Earth are used as sensors. We used dense GNSS networks in central Europe to detect and investigate a special type of plasma inhomogeneities, called travelling ionospheric disturbances (TID). Such use of GNSS sensors allows us to reconstruct the main TID parameters, such as spatial dimensions, velocities, and directions of their movement. The paper gives examples of the restoration of dynamic characteristics of ionospheric irregularities for quiet and disturbed geophysical conditions. Special attention is paid to the dynamics of ionospheric disturbances stimulated by the magnetic storms of two St. Patrick's Days (17 March 2013 and 2015). Additional opportunities for the remote sensing of the ionosphere with the use of dense regional networks of GNSS receiving sensors have been noted too. PMID- 28994719 TI - An IoT-Based Solution for Monitoring a Fleet of Educational Buildings Focusing on Energy Efficiency. AB - Raising awareness among young people and changing their behaviour and habits concerning energy usage is key to achieving sustained energy saving. Additionally, young people are very sensitive to environmental protection so raising awareness among children is much easier than with any other group of citizens. This work examines ways to create an innovative Information & Communication Technologies (ICT) ecosystem (including web-based, mobile, social and sensing elements) tailored specifically for school environments, taking into account both the users (faculty, staff, students, parents) and school buildings, thus motivating and supporting young citizens' behavioural change to achieve greater energy efficiency. A mixture of open-source IoT hardware and proprietary platforms on the infrastructure level, are currently being utilized for monitoring a fleet of 18 educational buildings across 3 countries, comprising over 700 IoT monitoring points. Hereon presented is the system's high-level architecture, as well as several aspects of its implementation, related to the application domain of educational building monitoring and energy efficiency. The system is developed based on open-source technologies and services in order to make it capable of providing open IT-infrastructure and support from different commercial hardware/sensor vendors as well as open-source solutions. The system presented can be used to develop and offer new app-based solutions that can be used either for educational purposes or for managing the energy efficiency of the building. The system is replicable and adaptable to settings that may be different than the scenarios envisioned here (e.g., targeting different climate zones), different IT infrastructures and can be easily extended to accommodate integration with other systems. The overall performance of the system is evaluated in real-world environment in terms of scalability, responsiveness and simplicity. PMID- 28994715 TI - beta-Amyloid and the Pathomechanisms of Alzheimer's Disease: A Comprehensive View. AB - Protein dyshomeostasis is the common mechanism of neurodegenerative diseases such as Alzheimer's disease (AD). Aging is the key risk factor, as the capacity of the proteostasis network declines during aging. Different cellular stress conditions result in the up-regulation of the neurotrophic, neuroprotective amyloid precursor protein (APP). Enzymatic processing of APP may result in formation of toxic Abeta aggregates (beta-amyloids). Protein folding is the basis of life and death. Intracellular Abeta affects the function of subcellular organelles by disturbing the endoplasmic reticulum-mitochondria cross-talk and causing severe Ca2+-dysregulation and lipid dyshomeostasis. The extensive and complex network of proteostasis declines during aging and is not able to maintain the balance between production and disposal of proteins. The effectivity of cellular pathways that safeguard cells against proteotoxic stress (molecular chaperones, aggresomes, the ubiquitin-proteasome system, autophagy) declines with age. Chronic cerebral hypoperfusion causes dysfunction of the blood-brain barrier (BBB), and thus the Abeta-clearance from brain-to-blood decreases. Microglia mediated clearance of Abeta also declines, Abeta accumulates in the brain and causes neuroinflammation. Recognition of the above mentioned complex pathogenesis pathway resulted in novel drug targets in AD research. PMID- 28994720 TI - Augmented Reality as a Telemedicine Platform for Remote Procedural Training. AB - Traditionally, rural areas in many countries are limited by a lack of access to health care due to the inherent challenges associated with recruitment and retention of healthcare professionals. Telemedicine, which uses communication technology to deliver medical services over distance, is an economical and potentially effective way to address this problem. In this research, we develop a new telepresence application using an Augmented Reality (AR) system. We explore the use of the Microsoft HoloLens to facilitate and enhance remote medical training. Intrinsic advantages of AR systems enable remote learners to perform complex medical procedures such as Point of Care Ultrasound (PoCUS) without visual interference. This research uses the HoloLens to capture the first-person view of a simulated rural emergency room (ER) through mixed reality capture (MRC) and serves as a novel telemedicine platform with remote pointing capabilities. The mentor's hand gestures are captured using a Leap Motion and virtually displayed in the AR space of the HoloLens. To explore the feasibility of the developed platform, twelve novice medical trainees were guided by a mentor through a simulated ultrasound exploration in a trauma scenario, as part of a pilot user study. The study explores the utility of the system from the trainees, mentor, and objective observers' perspectives and compares the findings to that of a more traditional multi-camera telemedicine solution. The results obtained provide valuable insight and guidance for the development of an AR-supported telemedicine platform. PMID- 28994722 TI - Design, Modeling and Synthesis of 1,2,3-Triazole-Linked Nucleoside-Amino Acid Conjugates as Potential Antibacterial Agents. AB - Copper-catalyzed azide-alkyne cycloadditions (CuAAC or click chemistry) are convenient methods to easily couple various pharmacophores or bioactive molecules. A new series of 1,2,3-triazole-linked nucleoside-amino acid conjugates have been designed and synthesized in 57-76% yields using CuAAC. The azido group was introduced on the 5'-position of uridine or the acyclic analogue using the tosyl-azide exchange method and alkylated serine or proparylglycine was the alkyne. Modeling studies of the conjugates in the active site of LpxC indicate they have promise as antibacterial agents. PMID- 28994723 TI - Middle Ear Prosthesis with Bactericidal Efficacy-In Vitro Investigation. AB - Materials used in ossicular replacement prostheses must possess appropriate biological properties, such as biocompatibility, stability, no cytotoxicity. Due to the risk of infection (otitis media and chronic otitis media), it is desirable to use an antibacterial agent for illness prevention during the ossicular reconstruction. The goal of this work was to observe biological properties of a new composite prosthesis made of ABS containing silver nanoparticles (AgNPs 45T). Samples for biological tests and then a prototype of middle ear prosthesis were prepared using injection moulding and extrusion techniques. In vitro experiments were carried out to assess bactericidal efficacy against Staphylococcus aureus and Pseudomona aeruginosa standard strains, cell proliferation, viability and cytotoxicity, using Hs680.Tr. fibroblast cells. Surface parameters of the samples were evaluated, including roughness and wettability. The silver ions were continually released from the polymer in aqueous solution. The silver ions release was measured as increasing with time and concentration of the silver nanoparticles in the polymer matrix. No cytotoxicity effect was observed, while bactericidal efficacy was noticed for silver nanoparticles. The roughness studies showed an increase in roughness for the samples with silver nanoparticles. All polymer and composite materials containing silver nanoparticles showed hydrophilic properties. The composites were found to release silver ions at a concentration level capable of rendering the antimicrobial efficacy even with the lowest concentration of silver nanoparticles in the material. Our results demonstrate that middle ear prosthesis made of polymer and silver nanoparticles may eliminate bacteria during inflammation in the middle ear. PMID- 28994724 TI - Identification of Metabolites of the Cardioprotective Alkaloid Dehydrocorydaline in Rat Plasma and Bile by Liquid Chromatography Coupled with Triple Quadrupole Linear Ion Trap Mass Spectrometry. AB - Dehydrocorydaline (DHC), a quaternary alkaloid from Corydalis yanhusuo, has been demonstrated to be the active constituent in the treatment of coronary heart disease. In this study, a high-performance liquid chromatography-electrospray ionization-triple quadrupole linear ion trap mass spectrometry (HPLC-ESI-QTRAP MS) technique was used to identify DHC metabolites in plasma and bile after oral administration of DHC to rats. A total of 18 metabolites (M1 to M18) were identified and characterized by LC-MS/MS in the positive ion mode. These 18 metabolites were all present in rat bile, while only 9 were detected in plasma. O demethylation, hydroxylation, di-hydroxylation, glucuronidation of O-demethyl DHC, sulfation of O-demethyl DHC and di-hydroxylation of dehydro-DHC were the major metabolic pathways of DHC. This is the first time that these metabolites of DHC have been identified in rat plasma and bile, which provides useful information for further analysis of the biotransformation of DHC and other quaternary protoberberine-type alkaloids. PMID- 28994721 TI - Natriuretic Peptides: The Case of Prostate Cancer. AB - Cardiac natriuretic peptides have long been known to act as main players in the homeostatic control of blood pressure, salt and water balance. However, in the last few decades, new properties have been ascribed to these hormones. A systematic review of English articles using MEDLINE Search terms included prostate cancer, inflammation, cardiac hormones, atrial natriuretic peptide, and brain natriuretic peptide. Most recent publications were selected. Natriuretic peptides are strongly connected to the immune system, whose two branches, innate and adaptive, are finely tuned and organized to kill invaders and repair injured tissues. These peptides control the immune response and act as anti-inflammatory and immune-modulatory agents. In addition, in cancers, natriuretic peptides have anti-proliferative effects by molecular mechanisms based on the inhibition/regulation of several pathways promoting cell proliferation and survival. Nowadays, it is accepted that chronic inflammation is a crucial player in prostate cancer development and progression. In this review, we summarize the current knowledge on the link between prostate cancer and inflammation and the potential use of natriuretic peptides as anti-inflammatory and anticancer agents. PMID- 28994725 TI - "He's the Number One Thing in My World": Application of the PRECEDE-PROCEED Model to Explore Child Car Seat Use in a Regional Community in New South Wales. AB - We explored the factors influencing the use of age-appropriate car seats in a community with a high proportion of Aboriginal families in regional New South Wales. We conducted a survey and three focus groups with parents of children aged 3-5 years enrolled at three early learning centres on the Australian south-east coast. Survey data were triangulated with qualitative data from focus groups and analysed using the PRECEDE-PROCEED conceptual framework. Of the 133 eligible families, 97 (73%) parents completed the survey including 31% of parents who reported their children were Aboriginal. Use of age-appropriate car seats was reported by 80 (83%) of the participants, and awareness of the child car seat legislation was high (91/97, 94%). Children aged 2-3 years were less likely reported to be restrained in an age-appropriate car seat than were older children aged 4-5 years (60% versus 95%: chi2 = 19.14, p < 0.001). Focus group participants highlighted how important their child's safety was to them, spoke of the influence grandparents had on their use of child car seats and voiced mixed views on the value of authorised child car seat fitters. Future programs should include access to affordable car seats and target community members as well as parents with clear, consistent messages highlighting the safety benefits of using age-appropriate car seats. PMID- 28994726 TI - Trap Nesting Wasps and Bees in Agriculture: A Comparison of Sown Wildflower and Fallow Plots in Florida. AB - Wildflower strip plantings in intensive agricultural systems have become a widespread tool for promoting pollination services and biological conservation because of their use by wasps and bees. Many of the trap-nesting wasps are important predators of common crop pests, and cavity-nesting bees that utilize trap-nests are important pollinators for native plants and many crops. The impact of wildflower strips on the nesting frequency of trap-nesting wasps or bees within localized areas has not been thoroughly investigated. Trap-nests made of bamboo reeds (Bambusa sp.) were placed adjacent to eight 0.1 ha wildflower plots and paired fallow areas (control plots) to determine if wildflower strips encourage the nesting of wasps and bees. From August 2014 to November 2015, occupied reeds were gathered and adults were collected as they emerged from the trap-nests. Treatment (wildflower or fallow plots) did not impact the number of occupied reeds or species richness of trap-nesting wasps using the occupied reeds. The wasps Pachodynerus erynnis, Euodynerus megaera, Parancistrocerus pedestris, and Isodontia spp. were the most common trap-nesting species collected. Less than 2% of the occupied reeds contained bees, and all were from the genus Megachile. The nesting wasp and bee species demonstrated preferences for reeds with certain inside diameters (IDs). The narrow range of ID preferences exhibited by each bee/wasp may provide opportunities to take advantage of their natural histories for biological control and/or pollination purposes. PMID- 28994729 TI - Tetraphenylpyrimidine-Based AIEgens: Facile Preparation, Theoretical Investigation and Practical Application. AB - Aggregation-induced emission (AIE) has become a hot research area and tremendous amounts of AIE-active luminogens (AIEgens) have been generated. To further promote the development of AIE, new AIEgens are highly desirable. Herein, new AIEgens based on tetraphenylpyrimidine (TPPM) are rationally designed according to the AIE mechanism of restriction of intramolecular motion, and facilely prepared under mild reaction conditions. The photophysical property of the generated TPPM, TPPM-4M and TPPM-4P are systematically investigated and the results show that they feature the aggregation-enhanced emission (AEE) characteristics. Theoretical study shows the high-frequency bending vibrations in the central pyrimidine ring of TPPM derivatives dominate the nonradiative decay channels. Thanks to the AEE feature, their aggregates can be used to detect explosives with super-amplification quenching effects, and the sensing ability is higher than typical AIE-active tetraphenylethene. It is anticipated that TPPM derivatives could serve as a new type of widely used AIEgen based on their facile preparation and good thermo-, photo- and chemostabilities. PMID- 28994727 TI - Biosensing Using Magnetic Particle Detection Techniques. AB - Magnetic particles are widely used as signal labels in a variety of biological sensing applications, such as molecular detection and related strategies that rely on ligand-receptor binding. In this review, we explore the fundamental concepts involved in designing magnetic particles for biosensing applications and the techniques used to detect them. First, we briefly describe the magnetic properties that are important for bio-sensing applications and highlight the associated key parameters (such as the starting materials, size, functionalization methods, and bio-conjugation strategies). Subsequently, we focus on magnetic sensing applications that utilize several types of magnetic detection techniques: spintronic sensors, nuclear magnetic resonance (NMR) sensors, superconducting quantum interference devices (SQUIDs), sensors based on the atomic magnetometer (AM), and others. From the studies reported, we note that the size of the MPs is one of the most important factors in choosing a sensing technique. PMID- 28994728 TI - Dose- and Ion-Dependent Effects in the Oxidative Stress Response to Space-Like Radiation Exposure in the Skeletal System. AB - Space radiation may pose a risk to skeletal health during subsequent aging. Irradiation acutely stimulates bone remodeling in mice, although the long-term influence of space radiation on bone-forming potential (osteoblastogenesis) and possible adaptive mechanisms are not well understood. We hypothesized that ionizing radiation impairs osteoblastogenesis in an ion-type specific manner, with low doses capable of modulating expression of redox-related genes. 16-weeks old, male, C57BL6/J mice were exposed to low linear-energy-transfer (LET) protons (150 MeV/n) or high-LET 56Fe ions (600 MeV/n) using either low (5 or 10 cGy) or high (50 or 200 cGy) doses at NASA's Space Radiation Lab. Five weeks or one year after irradiation, tissues were harvested and analyzed by microcomputed tomography for cancellous microarchitecture and cortical geometry. Marrow derived, adherent cells were grown under osteoblastogenic culture conditions. Cell lysates were analyzed by RT-PCR during the proliferative or mineralizing phase of growth, and differentiation was analyzed by imaging mineralized nodules. As expected, a high dose (200 cGy), but not lower doses, of either 56Fe or protons caused a loss of cancellous bone volume/total volume. Marrow cells produced mineralized nodules ex vivo regardless of radiation type or dose; 56Fe (200 cGy) inhibited osteoblastogenesis by more than 90% (5 weeks and 1 year post IR). After 5 weeks, irradiation (protons or 56Fe) caused few changes in gene expression levels during osteoblastogenesis, although a high dose 56Fe (200 cGy) increased Catalase and Gadd45. The addition of exogenous superoxide dismutase (SOD) protected marrow-derived osteoprogenitors from the damaging effects of exposure to low-LET (137Cs gamma) when irradiated in vitro, but had limited protective effects on high-LET 56Fe-exposed cells. In sum, either protons or 56Fe at a relatively high dose (200 cGy) caused persistent bone loss, whereas only high-LET 56Fe increased redox-related gene expression, albeit to a limited extent, and inhibited osteoblastogenesis. Doses below 50 cGy did not elicit widespread responses in any parameter measured. We conclude that high-LET irradiation at 200 cGy impaired osteoblastogenesis and regulated steady-state gene expression of select redox-related genes during osteoblastogenesis, which may contribute to persistent bone loss. PMID- 28994730 TI - PrLPAAT4, a Putative Lysophosphatidic Acid Acyltransferase from Paeonia rockii, Plays an Important Role in Seed Fatty Acid Biosynthesis. AB - Lysophosphatidic acid acyltransferases (LPAATs) are essential for the acylation of lysophosphatidic acid (LPA) and the synthesis of phosphatidic acid (PA), a key intermediate in the synthesis of membrane phospholipids and storage lipids. Here, a putative lysophosphatidic acid acyltransferase gene, designated PrLPAAT4, was isolated from seed unsaturated fatty acid (UFA)-rich P. rockii. The complete PrLPAAT4 cDNA contained a 1116-bp open reading frame (ORF), encoding a 42.9 kDa protein with 371 amino acid residues. Bioinformatic analysis indicates that PrLPAAT4 is a plasma membrane protein belonging to acyl-CoA:1-acylglycerol-sn-3 phosphate acyltranferases (AGPAT) family. PrLPAAT4 shared high sequence similarity with its homologs from Citrus clementina, Populus trichocarpa, Manihot esculenta, and Ricinus communis. In Arabidopsis, overexpression of PrLPAAT4 resulted in a significant increase in the content of oleic acid (OA) and total fatty acids (FAs) in seeds. AtDGAT1, AtGPAT9, and AtOleosin, involved in TAG assembly, were upregulated in PrLPAAT4-overexpressing lines. These results indicated that PrLPAAT4 functions may be as a positive regulator in seed FA biosynthesis. PMID- 28994731 TI - Validation of Foot Placement Locations from Ankle Data of a Kinect v2 Sensor. AB - The Kinect v2 sensor may be a cheap and easy to use sensor to quantify gait in clinical settings, especially when applied in set-ups integrating multiple Kinect sensors to increase the measurement volume. Reliable estimates of foot placement locations are required to quantify spatial gait parameters. This study aimed to systematically evaluate the effects of distance from the sensor, side and step length on estimates of foot placement locations based on Kinect's ankle body points. Subjects (n = 12) performed stepping trials at imposed foot placement locations distanced 2 m or 3 m from the Kinect sensor (distance), for left and right foot placement locations (side), and for five imposed step lengths. Body points' time series of the lower extremities were recorded with a Kinect v2 sensor, placed frontoparallelly on the left side, and a gold-standard motion registration system. Foot placement locations, step lengths, and stepping accuracies were compared between systems using repeated-measures ANOVAs, agreement statistics and two one-sided t-tests to test equivalence. For the right side at the 2 m distance from the sensor we found significant between-systems differences in foot placement locations and step lengths, and evidence for nonequivalence. This distance by side effect was likely caused by differences in body orientation relative to the Kinect sensor. It can be reduced by using Kinect's higher-dimensional depth data to estimate foot placement locations directly from the foot's point cloud and/or by using smaller inter-sensor distances in the case of a multi-Kinect v2 set-up to estimate foot placement locations at greater distances from the sensor. PMID- 28994733 TI - New Textile Sensors for In Situ Structural Health Monitoring of Textile Reinforced Thermoplastic Composites Based on the Conductive Poly(3,4 ethylenedioxythiophene)-poly(styrenesulfonate) Polymer Complex. AB - Many metallic structural and non-structural parts used in the transportation industry can be replaced by textile-reinforced composites. Composites made from a polymeric matrix and fibrous reinforcement have been increasingly studied during the last decade. On the other hand, the fast development of smart textile structures seems to be a very promising solution for in situ structural health monitoring of composite parts. In order to optimize composites' quality and their lifetime all the production steps have to be monitored in real time. Textile sensors embedded in the composite reinforcement and having the same mechanical properties as the yarns used to make the reinforcement exhibit actuating and sensing capabilities. This paper presents a new generation of textile fibrous sensors based on the conductive polymer complex poly(3,4-ethylenedioxythiophene) poly(styrenesulfonate) developed by an original roll to roll coating method. Conductive coating for yarn treatment was defined according to the preliminary study of percolation threshold of this polymer complex. The percolation threshold determination was based on conductive dry films' electrical properties analysis, in order to develop highly sensitive sensors. A novel laboratory equipment was designed and produced for yarn coating to ensure effective and equally distributed coating of electroconductive polymer without distortion of textile properties. The electromechanical properties of the textile fibrous sensors confirmed their suitability for in situ structural damages detection of textile reinforced thermoplastic composites in real time. PMID- 28994732 TI - Production of Single-Chain Fv Antibodies Specific for GA-Pyridine, an Advanced Glycation End-Product (AGE), with Reduced Inter-Domain Motion. AB - Due to their lower production cost compared with monoclonal antibodies, single chain variable fragments (scFvs) have potential for use in several applications, such as for diagnosis and treatment of a range of diseases, and as sensor elements. However, the usefulness of scFvs is limited by inhomogeneity through the formation of dimers, trimers, and larger oligomers. The scFv protein is assumed to be in equilibrium between the closed and open states formed by assembly or disassembly of VH and VL domains. Therefore, the production of an scFv with equilibrium biased to the closed state would be critical to overcome the problem in inhomogeneity of scFv for industrial or therapeutic applications. In this study, we obtained scFv clones stable against GA-pyridine, an advanced glycation end-product (AGE), by using a combination of a phage display system and random mutagenesis. Executing the bio-panning at 37 degrees C markedly improved the stability of scFvs. We further evaluated the radius of gyration by small angle X-ray scattering (SAXS), obtained compact clones, and also visualized open. PMID- 28994734 TI - Synthesis of 11C-Labelled Ureas by Palladium(II)-Mediated Oxidative Carbonylation. AB - Positron emission tomography is an imaging technique with applications in clinical settings as well as in basic research for the study of biological processes. A PET tracer, a biologically active molecule where a positron-emitting radioisotope such as carbon-11 has been incorporated, is used for the studies. Development of robust methods for incorporation of the radioisotope is therefore of the utmost importance. The urea functional group is present in many biologically active compounds and is thus an attractive target for incorporation of carbon-11 in the form of [11C]carbon monoxide. Starting with amines and [11C]carbon monoxide, both symmetrical and unsymmetrical 11C-labelled ureas were synthesised via a palladium(II)-mediated oxidative carbonylation and obtained in decay-corrected radiochemical yields up to 65%. The added advantage of using [11C]carbon monoxide was shown by the molar activity obtained for an inhibitor of soluble epoxide hydrolase (247 GBq/MUmol-319 GBq/MUmol). DFT calculations were found to support a reaction mechanism proceeding through an 11C-labelled isocyanate intermediate. PMID- 28994735 TI - Prediction Potential of Serum miR-155 and miR-24 for Relapsing Early Breast Cancer. AB - Oncogenic microRNAs (oncomiRs) accumulate in serum due to their increased stability and thus serve as biomarkers in breast cancer (BC) pathogenesis. Four oncogenic microRNAs (miR-155, miR-19a, miR-181b, and miR-24) and one tumor suppressor microRNA (let-7a) were shown to differentiate between high- and low risk early breast cancer (EBC) and reflect the surgical tumor removal and adjuvant therapy. Here we applied the longitudinal multivariate data analyses to stochastically model the serum levels of each of the oncomiRs using the RT-PCR measurements in the EBC patients (N = 133) that were followed up 4 years after diagnosis. This study identifies that two of the studied oncomiRs, miR-155 and miR-24, are highly predictive of EBC relapse. Furthermore, combining the oncomiR level with Ki-67 expression further specifies the relapse probability. Our data move further the notion that oncomiRs in serum enable not only monitoring of EBC but also are a very useful tool for predicting relapse independently of any other currently analyzed characteristics in EBC patients. Our approach can be translated into medical practice to estimate individual relapse risk of EBC patients. PMID- 28994737 TI - Anti-Inflammatory Pyranochalcone Derivative Attenuates LPS-Induced Acute Kidney Injury via Inhibiting TLR4/NF-kappaB Pathway. AB - Treatment of septic acute kidney injury (AKI) has still been beyond satisfaction, although anti-inflammatory therapy is beneficial for sepsis-induced AKI. Compound 5b was derived from natural pyranochalcones and exhibited potent anti inflammatory activity in adjuvant-induced arthritis. In this study, we aimed to investigate the renoprotective effects and potential mechanism of 5b against lipopolysaccharide (LPS)-induced AKI. C57BL/6 mice and human renal proximal tubule cell line (HK-2 cell) were treated with LPS, respectively. Compound 5b was orally administrated at a dose of 25 mg/kg/day for 5 days before LPS (10 mg/kg) intraperitoneal injection. Cells were pretreated with 25 MUg/mL 5b for 30 min before LPS (1 MUg/mL) treatment. Pretreatment with 5b markedly alleviated tubular injury and renal dysfunction in LPS-induced AKI. The expression of IL-1beta, IL 6, and TNF-alpha both in renal tissue of AKI mice and in the LPS-stimulated HK-2 cell culture medium were reduced by 5b treatment (p < 0.05). The results of immunohistochemistry staining showed that 5b reduced the expression of NF-kappaB p65 in kidneys. Similarly, 5b decreased the LPS-induced levels of NF-kappaB p65 and TLR4 proteins in kidneys and HK-2 cells. These data demonstrated that a potent pyranochalcone derivative, 5b, exhibited renoprotective effect against LPS induced AKI, which was associated with anti-inflammatory activity by inhibiting the TLR4/NF-kappaB pathway. PMID- 28994736 TI - A Review on the Phytochemistry, Pharmacology, Pharmacokinetics and Toxicology of Geniposide, a Natural Product. AB - Iridoid glycosides are natural products occurring widely in many herbal plants. Geniposide (C17H24O10) is a well-known one, present in nearly 40 species belonging to various families, especially the Rubiaceae. Along with this herbal component, dozens of its natural derivatives have also been isolated and characterized by researchers. Furthermore, a large body of pharmacological evidence has proved the various biological activities of geniposide, such as anti inflammatory, anti-oxidative, anti-diabetic, neuroprotective, hepatoprotective, cholagogic effects and so on. However, there have been some research articles on its toxicity in recent years. Therefore, this review paper aims to provide the researchers with a comprehensive profile of geniposide on its phytochemistry, pharmacology, pharmacokinetics and toxicology in order to highlight some present issues and future perspectives as well as to help us develop and utilize this iridoid glycoside more efficiently and safely. PMID- 28994738 TI - Single Silver Nanoparticle Instillation Induced Early and Persisting Moderate Cortical Damage in Rat Kidneys. AB - The potential toxic effects of silver nanoparticles (AgNPs), administered by a single intratracheal instillation (i.t), was assessed in a rat model using commercial physico-chemical characterized nanosilver. Histopathological changes, overall toxic response and oxidative stress (kidney and plasma protein carbonylation), paralleled by ultrastructural observations (TEM), were evaluated to examine renal responses 7 and 28 days after i.t. application of a low AgNP dose (50 ug/rat), compared to an equivalent dose of ionic silver (7 ug AgNO3/rat). The AgNPs caused moderate renal histopathological and ultrastructural alteration, in a region-specific manner, being the cortex the most affected area. Notably, the bulk AgNO3, caused similar adverse effects with a slightly more marked extent, also triggering apoptotic phenomena. Specifically, 7 days after exposure to both AgNPs and AgNO3, dilatation of the intercapillary and peripheral Bowman's space was observed, together with glomerular shrinkage. At day 28, these effects still persisted after both treatments, accompanied by an additional injury involving the vascular component of the mesangium, with interstitial micro hemorrhages. Neither AgNPs nor AgNO3 induced oxidative stress effects in kidneys and plasma, at either time point. The AgNP-induced moderate renal effects indicate that, despite their benefits, novel AgNPs employed in consumer products need exhaustive investigation to ensure public health safety. PMID- 28994740 TI - Antibacterial and Antitubercular Activities of Cinnamylideneacetophenones. AB - Cinnamaldehyde is a natural product with broad spectrum of antibacterial activity. In this work, it was used as a template for design and synthesis of a series of 17 cinnamylideneacetophenones. Phenolic compounds 3 and 4 exhibited MIC (minimum inhibitory concentration) and MBC (minimum bactericidal concentration) values of 77.9 to 312 uM against Staphylococcus aureus, Streptococcus mutans, and Streptococcus sanguinis. Compounds 2, 7, 10, and 18 presented potent effects against Mycobacterium tuberculosis (57.2 uM <= MIC <= 70.9 uM). Hydrophilic effects caused by substituents on ring B increased antibacterial activity against Gram-positive species. Thus, log Po/w were calculated by using high-performance liquid chromatography-photodiode array detection (HPLC-PDA) analyses, and cinnamylideneacetophenones presented values ranging from 2.5 to 4.1. In addition, the effects of 3 and 4 were evaluated on pulmonary cells, indicating their moderate toxicity (46.3 uM <= IC50 <= 96.7 uM) when compared with doxorubicin. Bioactive compounds were subjected to in silico prediction of pharmacokinetic properties, and did not violate Lipinski's and Veber's rules, corroborating their potential bioavailability by an oral route. PMID- 28994739 TI - Managing Early Childhood Caries with Atraumatic Restorative Treatment and Topical Silver and Fluoride Agents. AB - Early childhood caries (ECC) is a significant global health problem affecting millions of preschool children worldwide. In general, preschool children from families with 20% of the lowest family incomes suffered about 80% of the ECC. Most, if not all, surveys indicated that the great majority of ECC was left untreated. Untreated caries progresses into the dental pulp, causing pain and infection. It can spread systemically, affecting a child's growth, development and general health. Fundamental caries management is based on the conventional restorative approach. Because preschool children are too young to cope with lengthy dental treatment, they often receive dental treatment under general anaesthesia from a specialist dentist. However, treatment under general anaesthesia poses a life-threatening risk to young children. Moreover, there are few dentists in rural areas, where ECC is prevalent. Hence, conventional dental care is unaffordable, inaccessible or unavailable in many communities. However, studies showed that the atraumatic restorative treatment had a very good success rate in treating dentine caries in young children. Silver diamine fluoride is considered safe and effective in arresting dentine caries in primary teeth. The aim of this paper is to review and discuss updated evidence of these alternative approaches in order to manage cavitated ECC. PMID- 28994741 TI - Assessment of the Public Health Risks and Impact of a Tornado in Funing, China, 23 June 2016: A Retrospective Analysis. AB - (1) Background: Tornadoes are one of the deadliest disasters but their health impacts in China are poorly investigated. This study aimed to assess the public health risks and impact of an EF-4 tornado outbreak in Funing, China; (2) Methods: A retrospective analysis on the characteristics of tornado-related deaths and injuries was conducted based on the database from the Funing's Center for Disease Control and Prevention (CDC) and Funing People's Hospital. A change point time-series analysis of weekly incidence for the period January 2010 to September 2016 was used to identify sensitive infectious diseases to the tornado; (3) Results: The 75 to 84 years old group was at the highest risk of both death (RR = 82.16; 95% CIs = 19.66, 343.33) and injury (RR = 31.80; 95% CI = 17.26, 58.61), and females were at 53% higher risk of death than males (RR = 1.53; 95% CIs = 1.02, 2.29). Of the 337 injuries, 274 injuries (81%) were minor. Most deaths occurred indoors (87%) and the head (74%) was the most frequent site of trauma during the tornado. Five diseases showed downward change-points; (4) Conclusions: The experience of the Funing tornado underscores the relative danger of being indoors during a tornado and is successful in avoiding epidemics post tornado. Current international safety guidelines need modification when generalized to China. PMID- 28994742 TI - Blood Lead Levels and Learning Disabilities: A Cross-Sectional Study of the 2003 2004 National Health and Nutrition Examination Survey (NHANES). AB - Difficulties in the acquisition and use of listening, speaking, reading, writing, reasoning or mathematical abilities are present among persons diagnosed with learning disabilities (LDs). Previous studies suggest a significant relationship between lead (Pb) exposure and LDs. This study evaluated the potential dose response relationship between blood Pb levels and the risk of LDs. This cross sectional study examined 1411 children (32,788,743 weighted-persons) between 6 and 15 years old from the 2003-2004 National Health and Nutrition Examination Survey (NHANES) by analyzing demographics, health related-questions, and laboratory tests using survey logistic and frequency modeling in SAS. On a ug Pb/dL basis, a significant dose-dependent relationship between increasing blood Pb levels and increasing risk of LDs was observed (odds ratio (OR) = 1.21, 95% confidence interval (CI) = 1.03-1.43). The relationship remained significant when examining covariates such as gender and race (OR = 1.19, 95% CI = 1.00-1.40). By contrast, no dose-dependence was observed between increasing blood Pb levels and the risk of hay fever in the last year (OR = 0.77, 95% CI = 0.56-1.056), a non plausibly biologically related outcome of blood Pb levels. Persons in the 50th 75th (12.80%) and 75th-100th (17.14%) percentiles of blood Pb were significantly more likely to have LDs than persons in the 0-50th percentile of blood Pb (8.78%). An estimated 1 million persons born in the US from 1989 to 1998 developed LDs from elevated blood Pb levels. Overall, this study revealed a significant dose-dependent association between increasing childhood blood Pb levels and the risk of a LD diagnosis, but it was not possible to ascribe a direct cause-effect relationship between blood Pb exposure and LD diagnosis. Childhood Pb exposure should be considered when evaluating children with LDs, and continuing efforts should be made to reduce Pb exposure. PMID- 28994743 TI - An IoT-Based Computational Framework for Healthcare Monitoring in Mobile Environments. AB - The new Internet of Things paradigm allows for small devices with sensing, processing and communication capabilities to be designed, which enable the development of sensors, embedded devices and other 'things' ready to understand the environment. In this paper, a distributed framework based on the internet of things paradigm is proposed for monitoring human biomedical signals in activities involving physical exertion. The main advantages and novelties of the proposed system is the flexibility in computing the health application by using resources from available devices inside the body area network of the user. This proposed framework can be applied to other mobile environments, especially those where intensive data acquisition and high processing needs take place. Finally, we present a case study in order to validate our proposal that consists in monitoring footballers' heart rates during a football match. The real-time data acquired by these devices presents a clear social objective of being able to predict not only situations of sudden death but also possible injuries. PMID- 28994745 TI - Phosphorus-Sulfur Heterocycles Incorporating an O-P(S)-O or O-P(S)-S-S-P(S)-O Scaffold: One-Pot Synthesis and Crystal Structure Study. AB - A new one-pot preparative route was developed to synthesize novel organophosphorus-sulfur heterocycles via the reaction of the four-membered ring thionation reagent [2,4-diferrocenyl-1,3,2,4-diathiadiphosphetane 2,4-disulfide (FcLR, a ferrocene analogue of Lawesson's reagent)] and alkenyl/aryl-diols and I2 (or SOCl2) in the presence of triethylamine. Therefore, a series of five- to ten membered heterocycles bearing an O-P(S)-O or an O-P(S)-S-S-P(S)-O linkage were synthesized. The synthesis features a novel application of the multicomponent reaction, providing an efficient and environmentally benign method for the preparation of the unusual phosphorus-sulfur heterocycles. Seven representative X ray structures confirm the formation of these heterocycles. PMID- 28994744 TI - Multi-Contextual Segregation and Environmental Justice Research: Toward Fine Scale Spatiotemporal Approaches. AB - Many environmental justice studies have sought to examine the effect of residential segregation on unequal exposure to environmental factors among different social groups, but little is known about how segregation in non residential contexts affects such disparity. Based on a review of the relevant literature, this paper discusses the limitations of traditional residence-based approaches in examining the association between socioeconomic or racial/ethnic segregation and unequal environmental exposure in environmental justice research. It emphasizes that future research needs to go beyond residential segregation by considering the full spectrum of segregation experienced by people in various geographic and temporal contexts of everyday life. Along with this comprehensive understanding of segregation, the paper also highlights the importance of assessing environmental exposure at a high spatiotemporal resolution in environmental justice research. The successful integration of a comprehensive concept of segregation, high-resolution data and fine-grained spatiotemporal approaches to assessing segregation and environmental exposure would provide more nuanced and robust findings on the associations between segregation and disparities in environmental exposure and their health impacts. Moreover, it would also contribute to significantly expanding the scope of environmental justice research. PMID- 28994746 TI - Input Forces Estimation for Nonlinear Systems by Applying a Square-Root Cubature Kalman Filter. AB - This work presents a novel inverse algorithm to estimate time-varying input forces in nonlinear beam systems. With the system parameters determined, the input forces can be estimated in real-time from dynamic responses, which can be used for structural health monitoring. In the process of input forces estimation, the Runge-Kutta fourth-order algorithm was employed to discretize the state equations; a square-root cubature Kalman filter (SRCKF) was employed to suppress white noise; the residual innovation sequences, a priori state estimate, gain matrix, and innovation covariance generated by SRCKF were employed to estimate the magnitude and location of input forces by using a nonlinear estimator. The nonlinear estimator was based on the least squares method. Numerical simulations of a large deflection beam and an experiment of a linear beam constrained by a nonlinear spring were employed. The results demonstrated accuracy of the nonlinear algorithm. PMID- 28994748 TI - A Reliable and Real-Time Tracking Method with Color Distribution. AB - Occlusion is a challenging problem in visual tracking. Therefore, in recent years, many trackers have been explored to solve this problem, but most of them cannot track the target in real time because of the heavy computational cost. A spatio-temporal context (STC) tracker was proposed to accelerate the task by calculating context information in the Fourier domain, alleviating the performance in handling occlusion. In this paper, we take advantage of the high efficiency of the STC tracker and employ salient prior model information based on color distribution to improve the robustness. Furthermore, we exploit a scale pyramid for accurate scale estimation. In particular, a new high-confidence update strategy and a re-searching mechanism are used to avoid the model corruption and handle occlusion. Extensive experimental results demonstrate our algorithm outperforms several state-of-the-art algorithms on the OTB2015 dataset. PMID- 28994747 TI - A Perspective on the Experimental Techniques for Studying Lamins. AB - Lamins are type V intermediate filaments that collectively form a meshwork underneath the inner nuclear membrane, called nuclear lamina. Furthermore, they are also present in the nucleoplasm. Lamins are experiencing a growing interest, since a wide range of diseases are induced by mutations in the gene coding for A type lamins, globally known as laminopathies. Moreover, it has been demonstrated that lamins are involved in other pathological conditions, like cancer. The role of lamins has been studied from several perspectives, exploiting different techniques and procedures. This multidisciplinary approach has contributed to resolving the unique features of lamins and has provided a thorough insight in their role in living organisms. Yet, there are still many unanswered questions, which constantly generate research in the field. The present work is aimed to review some interesting experimental techniques performed so far to study lamins. Scientists can take advantage of this collection for their novel investigations, being aware of the already pursued and consolidated methodologies. Hopefully, advances in these research directions will provide insights to achieve better diagnostic procedures and effective therapeutic options. PMID- 28994749 TI - On Efficient Deployment of Wireless Sensors for Coverage and Connectivity in Constrained 3D Space. AB - Sensor networks have been used in a rapidly increasing number of applications in many fields. This work generalizes a sensor deployment problem to place a minimum set of wireless sensors at candidate locations in constrained 3D space to k-cover a given set of target objects. By exhausting the combinations of discreteness/continuousness constraints on either sensor locations or target objects, we formulate four classes of sensor deployment problems in 3D space: deploy sensors at Discrete/Continuous Locations (D/CL) to cover Discrete/Continuous Targets (D/CT). We begin with the design of an approximate algorithm for DLDT and then reduce DLCT, CLDT, and CLCT to DLDT by discretizing continuous sensor locations or target objects into a set of divisions without sacrificing sensing precision. Furthermore, we consider a connected version of each problem where the deployed sensors must form a connected network, and design an approximation algorithm to minimize the number of deployed sensors with connectivity guarantee. For performance comparison, we design and implement an optimal solution and a genetic algorithm (GA)-based approach. Extensive simulation results show that the proposed deployment algorithms consistently outperform the GA-based heuristic and achieve a close-to-optimal performance in small-scale problem instances and a significantly superior overall performance than the theoretical upper bound. PMID- 28994750 TI - Use of Immunolabeling to Analyze Stable, Dynamic, and Nascent Microtubules in the Zebrafish Embryo. AB - Microtubules (MTs) are dynamic and fragile structures that are challenging to image in vivo, particularly in vertebrate embryos. Immunolabeling methods are described here to analyze distinct populations of MTs in the developing neural tube of the zebrafish embryo. While the focus is on neural tissue, this methodology is broadly applicable to other tissues. The procedures are optimized for early to mid-somitogenesis-stage embryos (1 somite to 12 somites), however they can be adapted to a range of other stages with relatively minor adjustments. The first protocol provides a method to assess the spatial distribution of stable and dynamic MTs and perform a quantitative analysis of these populations with image-processing software. This approach complements existing tools to image microtubule dynamics and distribution in real-time, using transgenic lines or transient expression of tagged constructs. Indeed, such tools are very useful, however they do not readily distinguish between dynamic and stable MTs. The ability to image and analyze these distinct microtubule populations has important implications for understanding mechanisms underlying cell polarization and morphogenesis. The second protocol outlines a technique to analyze nascent MTs specifically. This is accomplished by capturing the de novo growth properties of MTs over time, following microtubule depolymerization with the drug nocodazole and a recovery period after drug washout. This technique has not yet been applied to the study of MTs in zebrafish embryos, but is a valuable assay for investigating the in vivo function of proteins implicated in microtubule assembly. PMID- 28994751 TI - Three-dimensional Imaging and Analysis of Mitochondria within Human Intraepidermal Nerve Fibers. AB - The goal of this protocol is to study mitochondria within intraepidermal nerve fibers. Therefore, 3D imaging and analysis techniques were developed to isolate nerve-specific mitochondria and evaluate disease-induced alterations of mitochondria in the distal tip of sensory nerves. The protocol combines fluorescence immunohistochemistry, confocal microscopy and 3D image analysis techniques to visualize and quantify nerve-specific mitochondria. Detailed parameters are defined throughout the procedures in order to provide a concrete example of how to use these techniques to isolate nerve-specific mitochondria. Antibodies were used to label nerve and mitochondrial signals within tissue sections of skin punch biopsies, which was followed by indirect immunofluorescence to visualize nerves and mitochondria with a green and red fluorescent signal respectively. Z-series images were acquired with confocal microscopy and 3D analysis software was used to process and analyze the signals. It is not necessary to follow the exact parameters described within, but it is important to be consistent with the ones chosen throughout the staining, acquisition and analysis steps. The strength of this protocol is that it is applicable to a wide variety of circumstances where one fluorescent signal is used to isolate other signals that would otherwise be impossible to study alone. PMID- 28994752 TI - A Technique for Subcutaneous Abdominal Adipose Tissue Biopsy via a Non-diathermy Method. AB - Adipose tissue biopsies offer tissue samples that, upon analysis, may provide insightful overviews of mechanisms relating to metabolism and disease. To obtain subcutaneous adipose tissue biopsies in the abdominal area, researchers and physicians use either a surgical or a needle-based technique. However, surgical subcutaneous fat biopsies can offer tissue samples that may provide a more comprehensive overview of the complexities of biological indices in white adipose tissue. Usually, a surgical adipose tissue biopsy includes a diathermy treatment for cauterizing blood vessels to prevent excessive bleeding. Nevertheless, side effects, such as flash fires and skin lesions in the tissue, have been reported after diathermy. Therefore, we aimed to standardize a surgical abdominal adipose tissue biopsy performed under local anesthesia using a non-diathermy method. We conducted 115 subcutaneous adipose tissue biopsies in healthy men using a non diathermy abdominal surgical biopsy method. Our results showed three cases of excessive post-operation bleeding out of 115 operations (2.61%).In conclusion, our standardized subcutaneous abdominal adipose tissue surgical biopsy using a non-diathermy method can be safely applied to healthy men at the bedside, with minimal side effects. PMID- 28994753 TI - Genome-wide Analysis of HDAC Inhibitor-mediated Modulation of microRNAs and mRNAs in B Cells Induced to Undergo Class-switch DNA Recombination and Plasma Cell Differentiation. AB - Antibody responses are accomplished through several critical B cell-intrinsic processes, including somatic hypermutation (SHM), class-switch DNA recombination (CSR), and plasma cell differentiation. In recent years, epigenetic modifications or factors, such as histone deacetylation and microRNAs (miRNAs), have been shown to interact with B-cell genetic programs to shape antibody responses, while the dysfunction of epigenetic factors has been found to lead to autoantibody responses. Analyzing genome-wide miRNA and mRNA expression in B cells in response to epigenetic modulators is important for understanding the epigenetic regulation of B-cell function and antibody response. Here, we demonstrate a protocol for inducing B cells to undergo CSR and plasma cell differentiation, treating these B cells with histone deacetylase (HDAC) inhibitors (HDIs), and analyzing mRNA and microRNA expression. In this protocol, we directly analyze complementary DNA (cDNA) sequences using next-generation mRNA sequencing (mRNA-seq) and miRNA-seq technologies, mapping of the sequencing reads to the genome, and quantitative reverse transcription (qRT)-PCR. With these approaches, we have defined that, in B cells induced to undergo CSR and plasma cell differentiation, HDI, an epigenetic regulator, selectively modulates miRNA and mRNA expression and alters CSR and plasma cell differentiation. PMID- 28994754 TI - A Magnetic Resonance Imaging Protocol for Stroke Onset Time Estimation in Permanent Cerebral Ischemia. AB - MRI provides a sensitive and specific imaging tool to detect acute ischemic stroke by means of a reduced diffusion coefficient of brain water. In a rat model of ischemic stroke, differences in quantitative T1 and T2 MRI relaxation times (qT1 and qT2) between the ischemic lesion (delineated by low diffusion) and the contralateral non-ischemic hemisphere increase with time from stroke onset. The time dependency of MRI relaxation time differences is heuristically described by a linear function and thus provides a simple estimate of stroke onset time. Additionally, the volumes of abnormal qT1 and qT2 within the ischemic lesion increase linearly with time providing a complementary method for stroke timing. A (semi)automated computer routine based on the quantified diffusion coefficient is presented to delineate acute ischemic stroke tissue in rat ischemia. This routine also determines hemispheric differences in qT1 and qT2 relaxation times and the location and volume of abnormal qT1 and qT2 voxels within the lesion. Uncertainties associated with onset time estimates of qT1 and qT2 MRI data vary from +/- 25 min to +/- 47 min for the first 5 hours of stroke. The most accurate onset time estimates can be obtained by quantifying the volume of overlapping abnormal qT1 and qT2 lesion volumes, termed 'Voverlap' (+/- 25 min) or by quantifying hemispheric differences in qT2 relaxation times only (+/- 28 min). Overall, qT2 derived parameters outperform those from qT1. The current MRI protocol is tested in the hyperacute phase of a permanent focal ischemia model, which may not be applicable to transient focal brain ischemia. PMID- 28994755 TI - Foodborne Pathogen Screening Using Magneto-fluorescent Nanosensor: Rapid Detection of E. Coli O157:H7. AB - Enterohemorrhagic Escherichia coli O157:H7 has been linked to both waterborne and foodborne illnesses, and remains a threat despite the food- and water-screening methods used currently. While conventional bacterial detection methods, such as polymerase chain reaction (PCR) and enzyme-linked immunosorbent assays (ELISA) can specifically detect pathogenic contaminants, they require extensive sample preparation and lengthy waiting periods. In addition, these practices demand sophisticated laboratory instruments and settings, and must be executed by trained professionals. Herein, a protocol is proposed for a simpler diagnostic technique that features the unique combination of magnetic and fluorescent parameters in a nanoparticle-based platform. The proposed multiparametric magneto fluorescent nanosensors (MFnS) can detect E. coli O157:H7 contamination with as little as 1 colony-forming unit present in solution within less than 1 h. Furthermore, the ability of MFnS to remain highly functional in complex media such as milk and lake water has been verified. Additional specificity assays were also used to demonstrate the ability of MFnS to only detect the specific target bacteria, even in the presence of similar bacterial species. The pairing of magnetic and fluorescent modalities allows for the detection and quantification of pathogen contamination in a wide range of concentrations, exhibiting its high performance in both early- and late-stage contamination detection. The effectiveness, affordability, and portability of the MFnS make them an ideal candidate for point-of-care screening for bacterial contaminants in a wide range of settings, from aquatic reservoirs to commercially packaged foods. PMID- 28994756 TI - Screening Assays to Characterize Novel Endothelial Regulators Involved in the Inflammatory Response. AB - The endothelial layer is essential for maintaining homeostasis in the body by controlling many different functions. Regulation of the inflammatory response by the endothelial layer is crucial to efficiently fight against harmful inputs and aid in the recovery of damaged areas. When the endothelial cells are exposed to an inflammatory environment, such as the outer component of gram-negative bacteria membrane, lipopolysaccharide (LPS), they express soluble pro inflammatory cytokines, such as Ccl5, Cxcl1 and Cxcl10, and trigger the activation of circulating leukocytes. In addition, the expression of adhesion molecules E-selectin, VCAM-1 and ICAM-1 on the endothelial surface enables the interaction and adhesion of the activated leukocytes to the endothelial layer, and eventually the extravasation towards the inflamed tissue. In this scenario, the endothelial function must be tightly regulated because excessive or defective activation in the leukocyte recruitment could lead to inflammatory-related disorders. Since many of these disorders do not have an effective treatment, novel strategies with a focus on the vascular layer must be investigated. We propose comprehensive assays that are useful to the search of novel endothelial regulators that modify leukocyte function. We analyze endothelial activation by using specific expression targets involved in leukocyte recruitment (such as, cytokines, chemokines, and adhesion molecules) with several techniques, including: real-time quantitative polymerase chain reaction (RT-qPCR), western blot, flow cytometry and adhesion assays. These approaches determine endothelial function in the inflammatory context and are very useful to perform screening assays to characterize novel endothelial inflammatory regulators that are potentially valuable for designing new therapeutic strategies. PMID- 28994757 TI - Determination of the Relative Potency of an Anti-TNF Monoclonal Antibody (mAb) by Neutralizing TNF Using an In Vitro Bioanalytical Method. AB - This protocol shows the measurement of the apoptotic activity neutralization of TNFalpha in a mouse fibroblast cell model (WEHI 164) using an anti-TNFalpha mAb. In addition, this protocol can be used to evaluate other anti-TNFalpha molecules, such as fusion proteins. The cellular model employed here is sensitive to TNFalpha-mediated apoptosis when an additional stress factor is induced in cell culture conditions (e.g., serum deprivation). This procedure exemplifies how to execute this analytical assay, highlighting the key operations relating to the sample preparation, cell dilution, apoptosis induction, and spectrophotometric measurements that are critical to ensure successful results. This protocol reveals the best-performance conditions relating to apoptosis induction and efficient signal recording, leading to low uncertainty values. PMID- 28994758 TI - Using Gold-standard Gait Analysis Methods to Assess Experience Effects on Lower limb Mechanics During Moderate High-heeled Jogging and Running. AB - A limited number of studies have explored lower-limb biomechanics during high heeled jogging and running, and most studies have failed to clarify the wearing experience of subjects. This protocol describes the differences in lower-limb kinematics and ground reaction force (GRF) between experienced wearers (EW) and inexperienced wearers (IEW) during moderate high-heeled jogging and running. A three-dimensional (3D) motion analysis system with a configured force platform was used to synchronously capture lower-limb joint movements and GRF. 36 young females volunteered to participate in this study and were asked about high-heeled shoe-wearing experience, including frequency, duration, heel types, and heel heights. Eleven who had the experience of 3 to 6 cm heels for a minimum of three days per week (6 h per day) for at least two years and eleven who wore high heels less than twice per month participated. Subjects performed jogging and running at comfortable low and high speeds, respectively, with the right foot completely stepping onto a force platform when passing by along a 10 m walkway. EW and IEW adopted different biomechanical adaptations while jogging and running. IEW exhibited a generally larger range of joint movement, while EW showed a dramatically larger loading rate of GRF during running. Hence, further studies on the lower-limb biomechanics of high-heeled gait should strictly control the wearing experience of the subjects. PMID- 28994759 TI - A Novel Method: Super-selective Adrenal Venous Sampling. AB - Primary aldosteronism (PA) and subclinical Cushing's syndrome (SCS) are conditions in which the adrenal glands autonomously produce excessive amounts of aldosterone and cortisol, respectively. The conventional adrenal venous sampling (cAVS) method collects blood samples from both adrenal central veins and is useful for identifying the laterality of excess hormone production in a unilateral lesion(s), as documented in PA cases. In cAVS, plasma cortisol concentrations (PCCs) are used to normalize plasma aldosterone concentrations (PACs). A novel "super-selective" adrenal venous sampling (ssAVS) method was developed using a micro-catheter, which collects blood samples from adrenal tributary veins (TVs). PACs in ssAVS samples do not require PCC normalization because samples contain a limited amount of systemic venous blood, if any. The ssAVS method enabled segmental lesion(s) to be detected in both adrenal glands, which may be treated by bilateral adrenalectomy, thereby sparing lesion-free segment(s). Right and left adrenals typically have three TVs each, i.e., the superior, lateral, and inferior TVs in the right adrenal as well as the superior median, superior-lateral, and lateral TVs in the left adrenal. In the ssAVS method, specific parent catheters and a technique to handle them are required, and have been described herein. Furthermore, ssAVS results from three cases of PA are presented: bilateral aldosterone-producing adenoma (APA) (Case #1), left APA and right possible cortisol-producing adenoma causing SCS (Case #2), and idiopathic hyperaldosteronism in which bilateral adrenal segments produced excessive amounts of aldosterone (Case #3). The ssAVS method is not difficult for expert angiographers, and, thus, is recommended worldwide to treat PA cases for which cAVS does not represent a viable surgical treatment option. PMID- 28994760 TI - Assessment of Sarcoplasmic Reticulum Calcium Reserve and Intracellular Diastolic Calcium Removal in Isolated Ventricular Cardiomyocytes. AB - Intracellular calcium recycling plays a critical role in regulation of systolic and diastolic function in cardiomyocytes. Cardiac sarcoplasmic reticulum (SR) serves as a Ca2+ reservoir for contraction, which reuptakes intracellular Ca2+ during relaxation. The SR Ca2+ reserve available for beats is determinate for cardiac contractibility, and the removal of intracellular Ca2+ is critical for cardiac diastolic function. Under some pathophysiological conditions, such as diabetes and heart failure, impaired calcium clearance and SR Ca2+ store in cardiomyocytes may be involved in the progress of cardiac dysfunction. Here, we describe a protocol to evaluate SRCa2+ reserve and diastolic Ca2+ removal. Briefly, a single cardiomyocyte was enzymatically isolated, and the intracellular Ca2+ fluorescence indicated by Fura-2 was recorded by a calcium imaging system. To employ caffeine for inducing total SR Ca2+ release, we preset an automatic perfusion switch program by interlinking the stimulation system and the perfusion system. Then, the mono-exponential curve fitting was used for analyzing decay time constants of calcium transients and caffeine-induced calcium pulses. Accordingly, the contribution of the SR Ca2+-ATPase (SERCA) and Na+-Ca2+ exchanger (NCX) to diastolic calcium removal was evaluated. PMID- 28994761 TI - Optical Coherence Tomography: Imaging Mouse Retinal Ganglion Cells In Vivo. AB - Structural changes in the retina are common manifestations of ophthalmic diseases. Optical coherence tomography (OCT) enables their identification in vivo rapidly, repetitively, and at a high resolution. This protocol describes OCT imaging in the mouse retina as a powerful tool to study optic neuropathies (OPN). The OCT system is an interferometry-based, non-invasive alternative to common post mortem histological assays. It provides a fast and accurate assessment of retinal thickness, allowing the possibility to track changes, such as retinal thinning or thickening. We present the imaging process and analysis with the example of the Opa1delTTAG mouse line. Three types of scans are proposed, with two quantification methods: standard and homemade calipers. The latter is best for use on the peripapillary retina during radial scans; being more precise, is preferable for analyzing thinner structures. All approaches described here are designed for retinal ganglion cells (RGC) but are easily adaptable to other cell populations. In conclusion, OCT is efficient in mouse model phenotyping and has the potential to be used for the reliable evaluation of therapeutic interventions. PMID- 28994762 TI - In Vitro Bioluminescence Assay to Characterize Circadian Rhythm in Mammary Epithelial Cells. AB - The circadian rhythm is a fundamental physiological process present in all organisms that regulates biological processes ranging from gene expression to sleep behavior. In vertebrates, circadian rhythm is controlled by a molecular oscillator that functions in both the suprachiasmatic nucleus (SCN; central pacemaker) and individual cells comprising most peripheral tissues. More importantly, disruption of circadian rhythm by exposure to light-at-night, environmental stressors and/or toxicants is associated with increased risk of chronic diseases and aging. The ability to identify agents that can disrupt central and/or peripheral biological clocks, and agents that can prevent or mitigate the effects of circadian disruption, has significant implications for prevention of chronic diseases. Although rodent models can be used to identify exposures and agents that induce or prevent/mitigate circadian disruption, these experiments require large numbers of animals. In vivo studies also require significant resources and infrastructure, and require researchers to work all night. Thus, there is an urgent need for a cell-type appropriate in vitro system to screen for environmental circadian disruptors and enhancers in cell types from different organs and disease states. We constructed a vector that drives transcription of the destabilized luciferase in eukaryotic cells under the control of the human PERIOD 2 gene promoter. This circadian reporter construct was stably transfected into human mammary epithelial cells, and circadian responsive reporter cells were selected to develop the in vitro bioluminescence assay. Here, we present a detailed protocol to establish and validate the assay. We further provide details for proof of concept experiments demonstrating the ability of our in vitro assay to recapitulate the in vivo effects of various chemicals on the cellular biological clock. The results indicate that the assay can be adapted to a variety of cell types to screen for both environmental disruptors and chemopreventive enhancers of circadian clocks. PMID- 28994763 TI - Effects of Transcranial Alternating Current Stimulation on the Primary Motor Cortex by Online Combined Approach with Transcranial Magnetic Stimulation. AB - Transcranial Alternating Current Stimulation (tACS) is a neuromodulatory technique able to act through sinusoidal electrical waveforms in a specific frequency and in turn modulate ongoing cortical oscillatory activity. This neurotool allows the establishment of a causal link between endogenous oscillatory activity and behavior. Most of the tACS studies have shown online effects of tACS. However, little is known about the underlying action mechanisms of this technique because of the AC-induced artifacts on Electroencephalography (EEG) signals. Here we show a unique approach to investigate online physiological frequency-specific effects of tACS of the primary motor cortex (M1) by using single pulse Transcranial Magnetic Stimulation (TMS) to probe cortical excitability changes. In our setup, the TMS coil is placed over the tACS electrode while Motor Evoked Potentials (MEPs) are collected to test the effects of the ongoing M1-tACS. So far, this approach has mainly been used to study the visual and motor systems. However, the current tACS-TMS setup can pave the way for future investigations of cognitive functions. Therefore, we provide a step-by step manual and video guidelines for the procedure. PMID- 28994764 TI - Patterning Bioactive Proteins or Peptides on Hydrogel Using Photochemistry for Biological Applications. AB - There are many biological stimuli that can influence cell behavior and stem cell differentiation. General cell culture approaches rely on soluble factors within the medium to control cell behavior. However, soluble additions cannot mimic certain signaling motifs, such as matrix-bound growth factors, cell-cell signaling, and spatial biochemical cues, which are common influences on cells. Furthermore, biophysical properties of the matrix, such as substrate stiffness, play important roles in cell fate, which is not easily manipulated using conventional cell culturing practices. In this method, we describe a straightforward protocol to provide patterned bioactive proteins on synthetic polyethylene glycol (PEG) hydrogels using photochemistry. This platform allows for the independent control of substrate stiffness and spatial biochemical cues. These hydrogels can achieve a large range of physiologically relevant stiffness values. Additionally, the surfaces of these hydrogels can be photopatterned with bioactive peptides or proteins via thiol-ene click chemistry reactions. These methods have been optimized to retain protein function after surface immobilization. This is a versatile protocol that can be applied to any protein or peptide of interest to create a variety of patterns. Finally, cells seeded onto the surfaces of these bioactive hydrogels can be monitored over time as they respond to spatially specific signals. PMID- 28994765 TI - Cardiopulmonary Bypass in a Mouse Model: A Novel Approach. AB - As prolonged cardiopulmonary bypass becomes more essential during cardiac interventions, an increasing clinical demand arises for procedure optimization and for minimizing organ damage resulting from prolonged extracorporal circulation. The goal of this paper was to demonstrate a fully functional and clinically relevant model of cardiopulmonary bypass in a mouse. We report on the device design, perfusion circuit optimization, and microsurgical techniques. This model is an acute model, which is not compatible with survival due to the need for multiple blood drawings. Because of the range of tools available for mice (e.g., markers, knockouts, etc.), this model will facilitate investigation into the molecular mechanisms of organ damage and the effect of cardiopulmonary bypass in relation to other comorbidities. PMID- 28994766 TI - Preparation of Liquid Crystal Networks for Macroscopic Oscillatory Motion Induced by Light. AB - A strategy based on doped liquid crystalline networks is described to create mechanical self-sustained oscillations of plastic films under continuous light irradiation. The photo-excitation of dopants that can quickly dissipate light into heat, coupled with anisotropic thermal expansion and self-shadowing of the film, gives rise to the self-sustained deformation. The oscillations observed are influenced by the dimensions and the modulus of the film, and by the directionality and intensity of the light. The system developed offers applications in energy conversion and harvesting for soft-robotics and automated systems. The general method described here consists of creating free-standing liquid crystalline films and characterizing the mechanical and thermal effects observed. The molecular alignment is achieved using alignment layers (rubbed polyimide), commonly used in the display manufacturing industry. To obtain actuators with large deformation, the mesogens are aligned and polymerized in a splay/bend configuration, i.e., with the director of the liquid crystals (LCs) going gradually from planar to homeotropic through the film thickness. Upon irradiation, the mechanical and thermal oscillations obtained are monitored with a high-speed camera. The results are further quantified by image analysis using an image processing program. PMID- 28994767 TI - Effects of Exposure of Formaldehyde to a Rat Model of Atopic Dermatitis Induced by Neonatal Capsaicin Treatment. AB - Atopic dermatitis is chronically relapsing pruritic eczema and prevails around the world especially in developed countries. Complex interactions between genetic and environmental factors are known to play an important role in the pathophysiology of atopic dermatitis. However, we still lack a detailed picture of the pathogenesis of this disease. Thus, it is of importance to develop appropriate animal models for elucidating the progression of atopic dermatitis. Moreover, investigating the effect of environmental factors such as air pollutants on atopic dermatitis expands understanding of the disease. Here, we describe a method for inducing atopic dermatitis in rats with neonatal capsaicin treatment and a protocol for exposure of a constant concentration of formaldehyde to rats to reveal effects on the development of atopic dermatitis in infantile and adolescent periods. These protocols have been successfully applied to several experiments and can be used for other substances. PMID- 28994768 TI - Using Virtual Reality to Transfer Motor Skill Knowledge from One Hand to Another. AB - As far as acquiring motor skills is concerned, training by voluntary physical movement is superior to all other forms of training (e.g. training by observation or passive movement of trainee's hands by a robotic device). This obviously presents a major challenge in the rehabilitation of a paretic limb since voluntary control of physical movement is limited. Here, we describe a novel training scheme we have developed that has the potential to circumvent this major challenge. We exploited the voluntary control of one hand and provided real-time movement-based manipulated sensory feedback as if the other hand is moving. Visual manipulation through virtual reality (VR) was combined with a device that yokes left-hand fingers to passively follow right-hand voluntary finger movements. In healthy subjects, we demonstrate enhanced within-session performance gains of a limb in the absence of voluntary physical training. Results in healthy subjects suggest that training with the unique VR setup might also be beneficial for patients with upper limb hemiparesis by exploiting the voluntary control of their healthy hand to improve rehabilitation of their affected hand. PMID- 28994769 TI - Isolation of Endothelial Progenitor Cells from Human Umbilical Cord Blood. AB - The existence of endothelial progenitor cells (EPCs) in peripheral blood and its involvement in vasculogenesis was first reported by Ashara and colleagues1. Later, others documented the existence of similar types of EPCs originating from bone marrow2,3. More recently, Yoder and Ingram showed that EPCs derived from umbilical cord blood had a higher proliferative potential compared to ones isolated from adult peripheral blood4,5,6. Apart from being involved in postnatal vasculogenesis, EPCs have also shown promise as a cell source for creating tissue engineered vascular and heart valve constructs7,8. Various isolation protocols exist, some of which involve the cell sorting of mononuclear cells (MNCs) derived from the sources mentioned earlier with the help of endothelial and hematopoietic markers, or culturing these MNCs with specialized endothelial growth medium, or a combination of these techniques9. Here, we present a protocol for the isolation and culture of EPCs using specialized endothelial medium supplemented with growth factors, without the use of immunosorting, followed by the characterization of the isolated cells using Western blotting and immunostaining. PMID- 28994770 TI - Intratracheal Inoculation of Fischer 344 Rats with Francisella tularensis. AB - Pulmonary infection with the bacterium Francisella tularensis can lead to the serious and potentially fatal disease, tularemia, in humans. Due to the current lack of an approved tularemia vaccine for humans, research is focused on vaccine development utilizing appropriate animal models. The Fischer 344 rat has emerged as a model that reflects human susceptibility to F. tularensis infection, and thus is an attractive model for tularemia vaccine development. Intratracheal inoculation of the Fischer 344 rat with F. tularensis mimics pulmonary exposure in humans. The successful delivery into the rat trachea is critical for pulmonary delivery. A laryngoscope with illumination is used to properly intubate the tracheae of anesthetized rats; the correct placement within the trachea is determined by a simple device to detect breathing. Following intubation, the F. tularensis culture is delivered in a measured dose via syringe. This technique standardizes pulmonary delivery of F. tularensis within the rat trachea to evaluate vaccine efficacy. PMID- 28994772 TI - In Situ Characterization of Boehmite Particles in Water Using Liquid SEM. AB - In situ imaging and elemental analysis of boehmite (AlOOH) particles in water is realized using the System for Analysis at the Liquid Vacuum Interface (SALVI) and Scanning Electron Microscopy (SEM). This paper describes the method and key steps in integrating the vacuum compatible SAVLI to SEM and obtaining secondary electron (SE) images of particles in liquid in high vacuum. Energy dispersive x ray spectroscopy (EDX) is used to obtain elemental analysis of particles in liquid and control samples including deionized (DI) water only and an empty channel as well. Synthesized boehmite (AlOOH) particles suspended in liquid are used as a model in the liquid SEM illustration. The results demonstrate that the particles can be imaged in the SE mode with good resolution (i.e., 400 nm). The AlOOH EDX spectrum shows significant signal from the aluminum (Al) when compared with the DI water and the empty channel control. In situ liquid SEM is a powerful technique to study particles in liquid with many exciting applications. This procedure aims to provide technical know-how in order to conduct liquid SEM imaging and EDX analysis using SALVI and to reduce potential pitfalls when using this approach. PMID- 28994771 TI - Semiautomated Longitudinal Microcomputed Tomography-based Quantitative Structural Analysis of a Nude Rat Osteoporosis-related Vertebral Fracture Model. AB - Osteoporosis-related vertebral compression fractures (OVCFs) are a common and clinically unmet need with increasing prevalence as the world population ages. Animal OVCF models are essential to the preclinical development of translational tissue engineering strategies. While a number of models currently exist, this protocol describes an optimized method for inducing multiple highly reproducible vertebral defects in a single nude rat. A novel longitudinal semiautomated microcomputed tomography (uCT)-based quantitative structural analysis of the vertebral defects is also detailed. Briefly, rats were imaged at multiple time points post-op. The day 1 scan was reoriented to a standard position, and a standard volume of interest was defined. Subsequent uCT scans of each rat were automatically registered to the day 1 scan so the same volume of interest was then analyzed to assess for new bone formation. This versatile approach can be adapted to a variety of other models where longitudinal imaging-based analysis could benefit from precise 3D semiautomated alignment. Taken together, this protocol describes a readily quantifiable and easily reproducible system for osteoporosis and bone research. The suggested protocol takes 4 months to induce osteoporosis in nude ovariectomized rats and between 2.7 and 4 h to generate, image, and analyze two vertebral defects, depending on tissue size and equipment. PMID- 28994774 TI - Establishment of Larval Zebrafish as an Animal Model to Investigate Trypanosoma cruzi Motility In Vivo. AB - Chagas disease is a parasitic infection caused by Trypanosoma cruzi, whose motility is not only important for localization, but also for cellular binding and invasion. Current animal models for the study of T. cruzi allow limited observation of parasites in vivo, representing a challenge for understanding parasite behavior during the initial stages of infection in humans. This protozoan has a flagellar stage in both vector and mammalian hosts, but there are no studies describing its motility in vivo.The objective of this project was to establish a live vertebrate zebrafish model to evaluate T. cruzi motility in the vascular system. Transparent zebrafish larvae were injected with fluorescently labeled trypomastigotes and observed using light sheet fluorescence microscopy (LSFM), a noninvasive method to visualize live organisms with high optical resolution. The parasites could be visualized for extended periods of time due to this technique's relatively low risk of photodamage compared to confocal or epifluorescence microscopy. T. cruzi parasites were observed traveling in the circulatory system of live zebrafish in different-sized blood vessels and the yolk. They could also be seen attached to the yolk sac wall and to the atrioventricular valve despite the strong forces associated with heart contractions. LSFM of T. cruzi-inoculated zebrafish larvae is a valuable method that can be used to visualize circulating parasites and evaluate their tropism, migration patterns, and motility in the dynamic environment of the cardiovascular system of a live animal. PMID- 28994773 TI - Improved Method for the Establishment of an In Vitro Blood-Brain Barrier Model Based on Porcine Brain Endothelial Cells. AB - The aim of this protocol presents an optimized procedure for the purification and cultivation of pBECs and to establish in vitro blood-brain barrier (BBB) models based on pBECs in mono-culture (MC), MC with astrocyte-conditioned medium (ACM), and non-contact co-culture (NCC) with astrocytes of porcine or rat origin. pBECs were isolated and cultured from fragments of capillaries from the brain cortices of domestic pigs 5-6 months old. These fragments were purified by careful removal of meninges, isolation and homogenization of grey matter, filtration, enzymatic digestion, and centrifugation. To further eliminate contaminating cells, the capillary fragments were cultured with puromycin-containing medium. When 60-95% confluent, pBECs growing from the capillary fragments were passaged to permeable membrane filter inserts and established in the models. To increase barrier tightness and BBB characteristic phenotype of pBECs, the cells were treated with the following differentiation factors: membrane permeant 8-CPT-cAMP (here abbreviated cAMP), hydrocortisone, and a phosphodiesterase inhibitor, RO-20-1724 (RO). The procedure was carried out over a period of 9-11 days, and when establishing the NCC model, the astrocytes were cultured 2-8 weeks in advance. Adherence to the described procedures in the protocol has allowed the establishment of endothelial layers with highly restricted paracellular permeability, with the NCC model showing an average transendothelial electrical resistance (TEER) of 1249 +/- 80 Omega cm2, and paracellular permeability (Papp) for Lucifer Yellow of 0.90 10-6 +/- 0.13 10-6 cm sec-1 (mean +/- SEM, n=55). Further evaluation of this pBEC phenotype showed good expression of the tight junctional proteins claudin 5, ZO-1, occludin and adherens junction protein p120 catenin. The model presented can be used for a range of studies of the BBB in health and disease and, with the highly restrictive paracellular permeability, this model is suitable for studies of transport and intracellular trafficking. PMID- 28994775 TI - Assessment of Human Adipose Tissue Microvascular Function Using Videomicroscopy. AB - While obesity is closely linked to the development of metabolic and cardiovascular disease, little is known about mechanisms that govern these processes. It is hypothesized that pro-atherogenic mediators released from fat tissues particularly in association with central/visceral adiposity may promote pathogenic vascular changes locally and systemically, and the notion that cardiovascular disease may be the consequence of adipose tissue dysfunction continues to evolve. Here, we describe a unique method of videomicroscopy that involves analysis of vasodilator and vasoconstrictor responses of intact small human arterioles removed from the adipose depot of living human subjects. Videomicroscopy is used to examine functional properties of isolated microvessels in response to pharmacological or physiological stimuli using a pressured system that mimics in vivo conditions. The technique is a useful approach to gain understanding of the pathophysiology and molecular mechanisms that contribute to vascular dysfunction locally within the adipose tissue milieu. Moreover, abnormalities in the adipose tissue microvasculature have also been linked with systemic diseases. We applied this technique to examine depot-specific vascular responses in obese subjects. We assessed endothelium-dependent vasodilation to both increased flow and acetylcholine in adipose arterioles (50 - 350 um internal diameter, 2 - 3 mm in length) isolated from two different adipose depots during bariatric surgery from the same individual. We demonstrated that arterioles from visceral fat exhibit impaired endothelium-dependent vasodilation compared to vessels isolated from the subcutaneous depot. The findings suggest that the visceral microenvironment is associated with vascular endothelial dysfunction which may be relevant to clinical observation linking increased visceral adiposity to systemic disease mechanisms. The videomicroscopy technique can be used to examine vascular phenotypes from different fat depots as well as compare findings across individuals with different degrees of obesity and metabolic dysfunction. The method can also be used to examine vascular responses longitudinally in response to clinical interventions. PMID- 28994776 TI - Single-molecule Manipulation of G-quadruplexes by Magnetic Tweezers. AB - Non-canonical nucleic acid secondary structure G-quadruplexes (G4) are involved in diverse cellular processes, such as DNA replication, transcription, RNA processing, and telomere elongation. During these processes, various proteins bind and resolve G4 structures to perform their function. As the function of G4 often depends on the stability of its folded structure, it is important to investigate how G4 binding proteins regulate the stability of G4. This work presents a method to manipulate single G4 molecules using magnetic tweezers, which enables studies of the regulation of G4 binding proteins on a single G4 molecule in real time. In general, this method is suitable for a wide scope of applications in studies for proteins/ligands interactions and regulations on various DNA or RNA secondary structures. PMID- 28994778 TI - Creation of a Dense Transposon Insertion Library Using Bacterial Conjugation in Enterobacterial Strains Such As Escherichia Coli or Shigella flexneri. AB - Transposon mutagenesis is a method that allows gene disruption via the random genomic insertion of a piece of DNA called a transposon. The protocol below outlines a method for high efficiency transfer between bacterial strains of a plasmid harboring a transposon containing a kanamycin resistance marker. The plasmid-borne transposase is encoded by a variant tnp gene that inserts the transposon into the genome of the recipient strain with very low insertional bias. This method thus allows the creation of large mutant libraries in which transposons have been inserted into unique genomic positions in a recipient strain of either Escherichia coli or Shigella flexneri bacteria. By using bacterial conjugation, as opposed to other methods such as electroporation or chemical transformation, large libraries with hundreds of thousands of unique clones can be created. This yields high-density insertion libraries, with insertions occurring as frequently as every 4-6 base pairs in non-essential genes. This method is superior to other methods as it allows for an inexpensive, easy to use, and high efficiency method for the creation of a dense transposon insertion library. The transposon library can be used in downstream applications such as transposon sequencing (Tn-Seq), to infer genetic interaction networks, or more simply, in mutational (forward genetic) screens. PMID- 28994777 TI - A General Method for Detecting Nitrosamide Formation in the In Vitro Metabolism of Nitrosamines by Cytochrome P450s. AB - N-nitrosamines are a well-established group of environmental carcinogens, which require cytochrome P450 oxidation to exhibit activity. The accepted mechanism of metabolic activation involves formation of alpha-hydroxynitrosamines that spontaneously decompose to DNA alkylating agents. Accumulation of DNA damage and the resulting mutations can ultimately lead to cancer. New evidence indicates that alpha-hydroxynitrosamines can be further oxidized to nitrosamides processively by cytochrome P450s. Because nitrosamides are generally more stable than alpha-hydroxynitrosamines and can also alkylate DNA, nitrosamides may play a role in carcinogenesis. In this report, we describe a general protocol for evaluating nitrosamide production from in vitro cytochrome P450-catalyzed metabolism of nitrosamines. This protocol utilizes a general approach to the synthesis of the relevant nitrosamides and an in vitro cytochrome P450 metabolism assay using liquid chromatography-nanospray ionization-high resolution tandem mass spectrometry for detection. This method detected N'-nitrosonorcotinine as a minor metabolite of N'-nitrosonornicotine in the example study. The method has high sensitivity and selectively due to accurate mass detection. Application of this method to a wide variety of nitrosamine-cytochrome P450 systems will help determine the generality of this transformation. Because cytochrome P450s are polymorphic and vary in activity, a better understanding of nitrosamide formation could aid in individual cancer risk assessment. PMID- 28994779 TI - Assessment of Dopaminergic Homeostasis in Mice by Use of High-performance Liquid Chromatography Analysis and Synaptosomal Dopamine Uptake. AB - Dopamine (DA) is a modulatory neurotransmitter controlling motor activity, reward processes and cognitive function. Impairment of dopaminergic (DAergic) neurotransmission is strongly associated with several central nervous system associated diseases such as Parkinson's disease, attention-deficit-hyperactivity disorder and drug addiction1,2,3,4. Delineating disease mechanisms involving DA imbalance is critically dependent on animal models to mimic aspects of the diseases, and thus protocols that assess specific parts of the DA homeostasis are important to provide novel insights and possible therapeutic targets for these diseases. Here, we present two useful experimental protocols that when combined provide a functional read-out of the DAergic system in mice. Biochemical and functional parameters on DA homeostasis are obtained through assessment of DA levels and dopamine transporter (DAT) functionality5. When investigating the DA system, the ability to reliably measure endogenous levels of DA from adult brain is essential. Therefore, we present how to perform high-performance liquid chromatography (HPLC) on brain tissue from mice to determine levels of DA. We perform the experiment on tissue from dorsal striatum (dStr) and nucleus accumbens (NAc), but the method is also suitable for other DA-innervated brain areas. DAT is essential for reuptake of DA into the presynaptic terminal, thereby controlling the temporal and spatial activity of released DA. Knowing the levels and functionality of DAT in the striatum is of major importance when assessing DA homeostasis. Here, we provide a protocol that allows to simultaneously deduce information on surface levels and function using a synaptosomal6 DA uptake assay. Current methods combined with standard immunoblotting protocols provide the researcher with relevant tools to characterize the DAergic system. PMID- 28994780 TI - A Test Bed to Examine Helmet Fit and Retention and Biomechanical Measures of Head and Neck Injury in Simulated Impact. AB - Conventional wisdom and the language in international helmet testing and certification standards suggest that appropriate helmet fit and retention during an impact are important factors in protecting the helmet wearer from impact induced injury. This manuscript aims to investigate impact-induced injury mechanisms in different helmet fit scenarios through analysis of simulated helmeted impacts with an anthropometric test device (ATD), an array of headform acceleration transducers and neck force/moment transducers, a dual high speed camera system, and helmet-fit force sensors developed in our research group based on Bragg gratings in optical fiber. To simulate impacts, an instrumented headform and flexible neck fall along a linear guide rail onto an anvil. The test bed allows simulation of head impact at speeds up to 8.3 m/s, onto impact surfaces that are both flat and angled. The headform is fit with a crash helmet and several fit scenarios can be simulated by making context specific adjustments to the helmet position index and/or helmet size. To quantify helmet retention, the movement of the helmet on the head is quantified using post-hoc image analysis. To quantify head and neck injury potential, biomechanical measures based on headform acceleration and neck force/moment are measured. These biomechanical measures, through comparison with established human tolerance curves, can estimate the risk of severe life threatening and/or mild diffuse brain injury and osteoligamentous neck injury. To our knowledge, the presented test-bed is the first developed specifically to assess biomechanical effects on head and neck injury relative to helmet fit and retention. PMID- 28994781 TI - Methods for Imaging Intracellular pH of the Follicle Stem Cell Lineage in Live Drosophila Ovarian Tissue. AB - Changes in intracellular pH (pHi) play important roles in the regulation of many cellular functions, including metabolism, proliferation, and differentiation. Typically, pHi dynamics are determined in cultured cells, which are amenable to measuring and experimentally manipulating pHi. However, the recent development of new tools and methodologies has made it possible to study pHi dynamics within intact, live tissue. For Drosophila research, one important development was the generation of a transgenic line carrying a pHi biosensor, mCherry::pHluorin. Here, we describe a protocol that we routinely use for imaging live Drosophila ovarioles to measure pHi in the epithelial follicle stem cell (FSC) lineage in mCherry::pHluorin transgenic wild type lines; however, the methods described here can be easily adapted for other tissues, including the wing discs and eye epithelium. We describe techniques for expressing mCherry::pHluorin in the FSC lineage, maintaining ovarian tissue during live imaging, and acquiring and analyzing images to obtain pHi values. PMID- 28994782 TI - Continuous Instream Monitoring of Nutrients and Sediment in Agricultural Watersheds. AB - Pollutant concentrations and loads in watersheds vary considerably with time and space. Accurate and timely information on the magnitude of pollutants in water resources is a prerequisite for understanding the drivers of the pollutant loads and for making informed water resource management decisions. The commonly used "grab sampling" method provides the concentrations of pollutants at the time of sampling (i.e., a snapshot concentration) and may under- or overpredict the pollutant concentrations and loads. Continuous monitoring of nutrients and sediment has recently received more attention due to advances in computing, sensing technology, and storage devices. This protocol demonstrates the use of sensors, sondes, and instrumentation to continuously monitor in situ nitrate, ammonium, turbidity, pH, conductivity, temperature, and dissolved oxygen (DO) and to calculate the loads from two streams (ditches) in two agricultural watersheds. With the proper calibration, maintenance, and operation of sensors and sondes, good water quality data can be obtained by overcoming challenging conditions such as fouling and debris buildup. The method can also be used in watersheds of various sizes and characterized by agricultural, forested, and/or urban land. PMID- 28994783 TI - Atomic Scale Structural Studies of Macromolecular Assemblies by Solid-state Nuclear Magnetic Resonance Spectroscopy. AB - Supramolecular protein assemblies play fundamental roles in biological processes ranging from host-pathogen interaction, viral infection to the propagation of neurodegenerative disorders. Such assemblies consist in multiple protein subunits organized in a non-covalent way to form large macromolecular objects that can execute a variety of cellular functions or cause detrimental consequences. Atomic insights into the assembly mechanisms and the functioning of those macromolecular assemblies remain often scarce since their inherent insolubility and non crystallinity often drastically reduces the quality of the data obtained from most techniques used in structural biology, such as X-ray crystallography and solution Nuclear Magnetic Resonance (NMR). We here present magic-angle spinning solid-state NMR spectroscopy (SSNMR) as a powerful method to investigate structures of macromolecular assemblies at atomic resolution. SSNMR can reveal atomic details on the assembled complex without size and solubility limitations. The protocol presented here describes the essential steps from the production of 13C/15N isotope-labeled macromolecular protein assemblies to the acquisition of standard SSNMR spectra and their analysis and interpretation. As an example, we show the pipeline of a SSNMR structural analysis of a filamentous protein assembly. PMID- 28994784 TI - Technique of Minimally Invasive Transverse Aortic Constriction in Mice for Induction of Left Ventricular Hypertrophy. AB - Transverse aortic constriction (TAC) in mice is one of the most commonly used surgical techniques for experimental investigation of pressure overload-induced left ventricular hypertrophy (LVH) and its progression to heart failure. In the majority of the reported investigations, this procedure is performed with intubation and ventilation of the animal which renders it demanding and time consuming and adds to the surgical burden to the animal. The aim of this protocol is to describe a simplified technique of minimally invasive TAC without intubation and ventilation of mice. Critical steps of the technique are emphasized in order to achieve low mortality and high efficiency in inducing LVH. Male C57BL/6 mice (10-week-old, 25-30 g, n=60) were anesthetized with a single intraperitoneal injection of a mixture of ketamine and xylazine. In a spontaneously breathing animal following a 3-4 mm upper partial sternotomy, a segment of 6/0 silk suture threaded through the eye of a ligation aid was passed under the aortic arch and tied over a blunted 27-gauge needle. Sham-operated animals underwent the same surgical preparation but without aortic constriction. The efficacy of the procedure in inducing LVH is attested by a significant increase in the heart/body weight ratio. This ratio is obtained at days 3, 7, 14 and 28 after surgery (n = 6 - 10 in each group and each time point). Using our technique, LVH is observed in TAC compared to sham animals from day 7 through day 28. Operative and late (over 28 days) mortalities are both very low at 1.7%. In conclusion, our cost-effective technique of minimally invasive TAC in mice carries very low operative and post-operative mortalities and is highly efficient in inducing LVH. It simplifies the operative procedure and reduces the strain put on the animal. It can be easily performed by following the critical steps described in this protocol. PMID- 28994785 TI - Aerosol-assisted Chemical Vapor Deposition of Metal Oxide Structures: Zinc Oxide Rods. AB - Whilst columnar zinc oxide (ZnO) structures in the form of rods or wires have been synthesized previously by different liquid- or vapor-phase routes, their high cost production and/or incompatibility with microfabrication technologies, due to the use of pre-deposited catalyst-seeds and/or high processing temperatures exceeding 900 degrees C, represent a drawback for a widespread use of these methods. Here, however, we report the synthesis of ZnO rods via a non catalyzed vapor-solid mechanism enabled by using an aerosol-assisted chemical vapor deposition (CVD) method at 400 degrees C with zinc chloride (ZnCl2) as the precursor and ethanol as the carrier solvent. This method provides both single step formation of ZnO rods and the possibility of their direct integration with various substrate types, including silicon, silicon-based micromachined platforms, quartz, or high heat resistant polymers. This potentially facilitates the use of this method at a large-scale, due to its compatibility with state-of the-art microfabrication processes for device manufacture. This report also describes the properties of these structures (e.g., morphology, crystalline phase, optical band gap, chemical composition, electrical resistance) and validates its gas sensing functionality towards carbon monoxide. PMID- 28994786 TI - Touchscreen Sustained Attention Task (SAT) for Rats. AB - Sustained attention is the ability to monitor intermittent and unpredictable events over a prolonged period of time. This attentional process subserves other aspects of cognition and is disrupted in certain neurodevelopmental, neuropsychiatric, and neurodegenerative disorders. Thus, it is clinically important to identify mechanisms that impair and improve sustained attention. Such mechanisms are often first discovered using rodent models. Therefore, several behavior procedures for testing aspects of sustained attention have been developed for rodents. One, first described by McGaughy and Sarter (1995), called the sustained attention task (SAT), trains rats to distinguish between signal (i.e., brief light presentation) and non-signal trials. The signals are short and thus require careful attention to be perceived. Attentional demands can be increased further by introducing a distractor (e.g., flashing houselight). We have modified this task for touchscreen operant chambers, which are configured with a touchscreen on one wall that can present stimuli and record responses. Here we detail our protocol for SAT in touchscreen chambers. Additionally, we present standard measures of performance in male and female Sprague-Dawley rats. Comparable performance on this task in both sexes highlights its use for attention studies, especially as more researchers are including female rodents in their experimental design. Moreover, the easy implementation of SAT for the increasingly popular touchscreen chambers increases its utility. PMID- 28994787 TI - In Situ MHC-tetramer Staining and Quantitative Analysis to Determine the Location, Abundance, and Phenotype of Antigen-specific CD8 T Cells in Tissues. AB - T cells are critical to many immunological processes, including detecting and eliminating virus-infected cells, preventing autoimmunity, assisting in B-cell and plasma-cell production of antibodies, and detecting and eliminating cancer cells. The development of MHC-tetramer staining of antigen-specific T cells analyzed by flow cytometry has revolutionized our ability to study and understand the immunobiology of T cells. While extremely useful for determining the quantity and phenotype of antigen-specific T cells, flow cytometry cannot determine the spatial localization of antigen-specific T cells to other cells and structures in tissues, and current disaggregation techniques to extract the T cells needed for flow cytometry have limited effectiveness in non-lymphoid tissues. In situ MHC tetramer staining (IST) is a technique to visualize T cells that are specific for antigens of interest in tissues. In combination with immunohistochemistry (IHC), IST can determine the abundance, location, and phenotype of antigen-specific CD8 and CD4 T cells in tissues. Here, we describe a protocol to stain and enumerate antigen-specific CD8 T cells, with specific phenotypes located within specific tissue compartments. These procedures are the same that we used in our recent publication by Li et al., entitled "Simian Immunodeficiency Virus-Producing Cells in Follicles Are Partially Suppressed by CD8+ Cells In Vivo." The methods described are broadly applicable because they can be used to localize, phenotype, and quantify essentially any antigen-specific CD8 T cell for which MHC tetramers are available, in any tissue. PMID- 28994788 TI - Evaluating Primary Blast Effects In Vitro. AB - Exposure to blast events can cause severe trauma to vital organs such as the lungs, ears, and brain. Understanding the mechanisms behind such blast-induced injuries is of great importance considering the recent trend towards the use of explosives in modern warfare and terrorist-related incidents. To fully understand blast-induced injury, we must first be able to replicate such blast events in a controlled environment using a reproducible method. In this technique using shock tube equipment, shock waves at a range of pressures can be propagated over live cells grown in 2D, and markers of cell viability can be immediately analyzed using a redox indicator assay and the fluorescent imaging of live and dead cells. This method demonstrated that increasing the peak blast overpressure to 127 kPa can stimulate a significant drop in cell viability when compared to untreated controls. Test samples are not limited to adherent cells, but can include cell suspensions, whole-body and tissue samples, through minor modifications to the shock tube setup. Replicating the exact conditions that tissues and cells experience when exposed to a genuine blast event is difficult. Techniques such as the one presented in this article can help to define damage thresholds and identify the transcriptional and epigenetic changes within cells that arise from shock wave exposure. PMID- 28994789 TI - Focal Macropatch Recordings of Synaptic Currents from the Drosophila Larval Neuromuscular Junction. AB - Drosophila neuromuscular junction (NMJ) is an excellent model system to study glutamatergic synaptic transmission. We describe the technique of focal macropatch recordings of synaptic currents from visualized boutons at the Drosophila larval NMJ. This technique requires customized fabrication of recording micropipettes, as well as a compound microscope equipped with a high magnification, long-distance water immersion objective, differential interference contrast (DIC) optics, and a fluorescent attachment. The recording electrode is positioned on the top of a selected synaptic bouton visualized with DIC optics, epi-fluorescence, or both. The advantage of this technique is that it allows monitoring the synaptic activity of a limited number of sites of release. The recording electrode has a diameter of several microns, and the release sites positioned outside of the electrode rim do not significantly affect the recorded currents. The recorded synaptic currents have fast kinetics and can be readily resolved. These advantages are especially important for the studies of mutant fly lines with enhanced spontaneous or asynchronous synaptic activity. PMID- 28994790 TI - Modelling Zika Virus Infection of the Developing Human Brain In Vitro Using Stem Cell Derived Cerebral Organoids. AB - The recent emergence of Zika virus (ZIKV) in susceptible populations has led to an abrupt increase in microcephaly and other neurodevelopmental conditions in newborn infants. While mosquitos are the main route of viral transmission, it has also been shown to spread via sexual contact and vertical mother-to-fetus transmission. In this latter case of transmission, due to the unique viral tropism of ZIKV, the virus is believed to predominantly target the neural progenitor cells (NPCs) of the developing brain. Here a method for modeling ZIKV infection, and the resulting microcephaly, that occur when human cerebral organoids are exposed to live ZIKV is described. The organoids display high levels of virus within their neural progenitor population, and exhibit severe cell death and microcephaly over time. This three-dimensional cerebral organoid model allows researchers to conduct species-matched experiments to observe and potentially intervene with ZIKV infection of the developing human brain. The model provides improved relevance over standard two-dimensional methods, and contains human-specific cellular architecture and protein expression that are not possible in animal models. PMID- 28994791 TI - Subcellular Fractionation for ERK Activation Upon Mitochondrial-derived Peptide Treatment. AB - Mitochondrial-derived peptides (MDPs) are a new class of peptides that are encoded by small open reading frames within other known genes of the mitochondrial genome. MDPs have a wide variety of biological effects such as protecting neurons from apoptosis, improving metabolic markers, and protecting cells from chemotherapy. Humanin was the first MDP to be discovered and is the most studied peptide among the MDP family. The membrane receptors and downstream signaling pathways of humanin have been carefully characterized. Additional MDPs such as MOTS-c and SHLP1-6 have been more recently discovered and the signaling mechanisms have yet to be elucidated. Here we describe a cell culture based method to determine the function of these peptides. In particular, cell fractionation techniques in combination with western blotting allow for the quantitative determination of activation and translocation of important signaling molecule. While there are other methods of cell fractionation, the one described here is an easy and straightforward method. These methods can be used to further elucidate the mechanism of action of these peptides and other therapeutic agents. PMID- 28994792 TI - The Rabbit Model of Accelerated Atherosclerosis: A Methodological Perspective of the Iliac Artery Balloon Injury. AB - Acute coronary syndrome resulting from coronary occlusion following atherosclerotic plaque development and rupture is the leading cause of death in the industrialized world. New Zealand White (NZW) rabbits are widely used as an animal model for the study of atherosclerosis. They develop spontaneous lesions when fed with atherogenic diet; however, this requires long time of 4 - 8 months. To further enhance and accelerate atherogenesis, a combination of atherogenic diet and mechanical endothelial injury is often employed. The presented procedure for inducing atherosclerotic plaques in rabbits uses a balloon catheter to disrupt the endothelium in the left iliac artery of NZW rabbits fed with atherogenic diet. Such mechanical damage caused by the balloon catheter induces a chain of inflammatory reactions initiating neointimal lipid accumulation in a time dependent fashion. Atherosclerotic plaque following balloon injury show neointimal thickening with extensive lipid infiltration, high smooth muscle cell content and presence of macrophage derived foam cells. This technique is simple, reproducible and produces plaque of controlled length within the iliac artery. The whole procedure is completed within 20 - 30 min. The procedure is safe with low mortality and also offers high success in obtaining substantial intimal lesions. The procedure of balloon catheter induced arterial injury results in atherosclerosis within two weeks. This model can be used for investigating the disease pathology, diagnostic imaging and to evaluate new therapeutic strategies. PMID- 28994794 TI - High-speed Continuous-wave Stimulated Brillouin Scattering Spectrometer for Material Analysis. AB - Recent years have witnessed a significant increase in the use of spontaneous Brillouin spectrometers for non-contact analysis of soft matter, such as aqueous solutions and biomaterials, with fast acquisition times. Here, we discuss the assembly and operation of a Brillouin spectrometer that uses stimulated Brillouin scattering (SBS) to measure stimulated Brillouin gain (SBG) spectra of water and lipid emulsion-based tissue-like samples in transmission mode with <10 MHz spectral-resolution and <35 MHz Brillouin-shift measurement precision at <100 ms. The spectrometer consists of two nearly counter-propagating continuous-wave (CW) narrow-linewidth lasers at 780 nm whose frequency detuning is scanned through the material Brillouin shift. By using an ultra-narrowband hot rubidium-85 vapor notch filter and a phase-sensitive detector, the signal-to-noise-ratio of the SBG signal is significantly enhanced compared to that obtained with existing CW-SBS spectrometers. This improvement enables measurement of SBG spectra with up to 100 fold faster acquisition times, thereby facilitating high spectral-resolution and high-precision Brillouin analysis of soft materials at high speed. PMID- 28994793 TI - Biochemical and Structural Characterization of the Carbohydrate Transport Substrate-binding-protein SP0092. AB - Development of new antimicrobials and vaccines for Streptococcus pneumoniae (pneumococcus) are necessary to halt the rapid rise in multiple resistant strains. Carbohydrate substrate binding proteins (SBPs) represent viable targets for the development of protein-based vaccines and new antimicrobials because of their extracellular localization and the centrality of carbohydrate import for pneumococcal metabolism, respectively. Described here is a rationalized integrated protocol to carry out a comprehensive characterization of SP0092, which can be extended to other carbohydrate SBPs from the pneumococcus and other bacteria. This procedure can aid the structure-based design of inhibitors for this class of proteins. Presented in the first part of this manuscript are protocols for biochemical analysis by thermal shift assay, multi angle light scattering (MALS), and size exclusion chromatography (SEC), which optimize the stability and homogeneity of the sample directed to crystallization trials and so enhance the probability of success. The second part of this procedure describes the characterization of the SBP crystals using a tunable wavelength anomalous diffraction synchrotron beamline, and data collection protocols for measuring data that can be used to resolve the crystallized protein structure. PMID- 28994795 TI - A Method to Estimate Cadaveric Femur Cortical Strains During Fracture Testing Using Digital Image Correlation. AB - This protocol describes the method using digital image correlation to estimate cortical strain from high speed video images of the cadaveric femoral surface obtained from mechanical testing. This optical method requires a texture of many contrasting fiduciary marks on a solid white background for accurate tracking of surface deformation as loading is applied to the specimen. Immediately prior to testing, the surface of interest in the camera view is painted with a water-based white primer and allowed to dry for several minutes. Then, a black paint is speckled carefully over the white background with special consideration for the even size and shape of the droplets. Illumination is carefully designed and set such that there is optimal contrast of these marks while minimizing reflections through the use of filters. Images were obtained through high speed video capture at up to 12,000 frames/s. The key images prior to and including the fracture event are extracted and deformations are estimated between successive frames in carefully sized interrogation windows over a specified region of interest. These deformations are then used to compute surface strain temporally during the fracture test. The strain data is very useful for identifying fracture initiation within the femur, and for eventual validation of proximal femur fracture strength models derived from Quantitative Computed Tomography-based Finite Element Analysis (QCT/FEA). PMID- 28994796 TI - The Knob Supination Task: A Semi-automated Method for Assessing Forelimb Function in Rats. AB - Tasks that accurately measure dexterity in animal models are critical to understand hand function. Current rat behavioral tasks that measure dexterity largely use video analysis of reaching or food manipulation. While these tasks are easy to implement and are robust across disease models, they are subjective and laborious for the experimenter. Automating traditional tasks or creating new automated tasks can make the tasks more efficient, objective, and quantitative. Since rats are less dexterous than primates, central nervous system (CNS) injury produces more subtle deficits in dexterity, however, supination is highly affected in rodents and crucial to hand function in primates. Therefore, we designed a semi-automated task that measures forelimb supination in rats. Rats are trained to reach and grasp a knob-shaped manipulandum and turn the manipulandum in supination to receive a reward. Rats can acquire the skill within 20 +/- 5 days. While the early part of training is highly supervised, much of the training is done without direct supervision. The task reliably and reproducibly captures subtle deficits after injury and shows functional recovery that accurately reflects clinical recovery curves. Analysis of data is performed by specialized software through a graphical user interface that is designed to be intuitive. We also give solutions to common problems encountered during training, and show that minor corrections to behavior early in training produce reliable acquisition of supination. Thus, the knob supination task provides efficient and quantitative evaluation of a critical movement for dexterity in rats. PMID- 28994797 TI - Sequential Salt Extractions for the Analysis of Bulk Chromatin Binding Properties of Chromatin Modifying Complexes. AB - Elucidation of the binding properties of chromatin-targeting proteins can be very challenging due to the complex nature of chromatin and the heterogeneous nature of most mammalian chromatin-modifying complexes. In order to overcome these hurdles, we have adapted a sequential salt extraction (SSE) assay for evaluating the relative binding affinities of chromatin-bound complexes. This easy and straightforward assay can be used by non-experts to evaluate the relative difference in binding affinity of two related complexes, the changes in affinity of a complex when a subunit is lost or an individual domain is inactivated, and the change in binding affinity after alterations to the chromatin landscape. By sequentially re-suspending bulk chromatin in increasing amounts of salt, we are able to profile the elution of a particular protein from chromatin. Using these profiles, we are able to determine how alterations in a chromatin-modifying complex or alterations to the chromatin environment affect binding interactions. Coupling SSE with other in vitro and in vivo assays, we can determine the roles of individual domains and proteins on the functionality of a complex in a variety of chromatin environments. PMID- 28994798 TI - Large Volume, Behaviorally-relevant Illumination for Optogenetics in Non-human Primates. AB - This protocol describes a large-volume illuminator, which was developed for optogenetic manipulations in the non-human primate brain. The illuminator is a modified plastic optical fiber with etched tip, such that the light emitting surface area is > 100x that of a conventional fiber. In addition to describing the construction of the large-volume illuminator, this protocol details the quality-control calibration used to ensure even light distribution. Further, this protocol describes techniques for inserting and removing the large volume illuminator. Both superficial and deep structures may be illuminated. This large volume illuminator does not need to be physically coupled to an electrode, and because the illuminator is made of plastic, not glass, it will simply bend in circumstances when traditional optical fibers would shatter. Because this illuminator delivers light over behaviorally-relevant tissue volumes (~ 10 mm3) with no greater penetration damage than a conventional optical fiber, it facilitates behavioral studies using optogenetics in non-human primates. PMID- 28994799 TI - The C. elegans Intestine As a Model for Intercellular Lumen Morphogenesis and In Vivo Polarized Membrane Biogenesis at the Single-cell Level: Labeling by Antibody Staining, RNAi Loss-of-function Analysis and Imaging. AB - Multicellular tubes, fundamental units of all internal organs, are composed of polarized epithelial or endothelial cells, with apical membranes lining the lumen and basolateral membranes contacting each other and/or the extracellular matrix. How this distinctive membrane asymmetry is established and maintained during organ morphogenesis is still an unresolved question of cell biology. This protocol describes the C. elegans intestine as a model for the analysis of polarized membrane biogenesis during tube morphogenesis, with emphasis on apical membrane and lumen biogenesis. The C. elegans twenty-cell single-layered intestinal epithelium is arranged into a simple bilaterally symmetrical tube, permitting analysis on a single-cell level. Membrane polarization occurs concomitantly with polarized cell division and migration during early embryogenesis, but de novo polarized membrane biogenesis continues throughout larval growth, when cells no longer proliferate and move. The latter setting allows one to separate subcellular changes that simultaneously mediate these different polarizing processes, difficult to distinguish in most polarity models. Apical-, basolateral membrane-, junctional-, cytoskeletal- and endomembrane components can be labeled and tracked throughout development by GFP fusion proteins, or assessed by in situ antibody staining. Together with the organism's genetic versatility, the C. elegans intestine thus provides a unique in vivo model for the visual, developmental, and molecular genetic analysis of polarized membrane and tube biogenesis. The specific methods (all standard) described here include how to: label intestinal subcellular components by antibody staining; analyze genes involved in polarized membrane biogenesis by loss-of-function studies adapted to the typically essential tubulogenesis genes; assess polarity defects during different developmental stages; interpret phenotypes by epifluorescence, differential interference contrast (DIC) and confocal microscopy; quantify visual defects. This protocol can be adapted to analyze any of the often highly conserved molecules involved in epithelial polarity, membrane biogenesis, tube and lumen morphogenesis. PMID- 28994800 TI - Fabrication and Validation of an Organ-on-chip System with Integrated Electrodes to Directly Quantify Transendothelial Electrical Resistance. AB - Organs-on-chips, in vitro models involving the culture of (human) tissues inside microfluidic devices, are rapidly emerging and promise to provide useful research tools for studying human health and disease. To characterize the barrier function of cell layers cultured inside organ-on-chip devices, often transendothelial or transepithelial electrical resistance (TEER) is measured. To this end, electrodes are usually integrated into the chip by micromachining methods to provide more stable measurements than is achieved with manual insertion of electrodes into the inlets of the chip. However, these electrodes frequently hamper visual inspection of the studied cell layer or require expensive cleanroom processes for fabrication. To overcome these limitations, the device described here contains four easily integrated electrodes that are placed and fixed outside of the culture area, making visual inspection possible. Using these four electrodes the resistance of six measurement paths can be quantified, from which the TEER can be directly isolated, independent of the resistance of culture medium-filled microchannels. The blood-brain barrier was replicated in this device and its TEER was monitored to show the device applicability. This chip, the integrated electrodes and the TEER determination method are generally applicable in organs on-chips, both to mimic other organs or to be incorporated into existing organ-on chip systems. PMID- 28994802 TI - Use of a Rat Model to Study Ventral Abdominal Hernia Repair. AB - Ventral abdominal hernia is a relatively common clinical condition that sometimes requires herniorraphy (surgical repair). The repair of ventral abdominal hernia typically requires implantation of a material to serve as a mechanical bridge across the defect in the abdominal wall. Biomaterials, such as porcine small intestinal submucosa (SIS), also serve as a lattice for cell growth into the implant and can naturally incorporate into the host tissue. Development of such repair materials benefits from use of animal models in which experimental abdominal wall defects are easily created and are amenable to repair in a reproducible fashion. The method offered here describes surgical creation and repair of ventral abdominal hernia in a rat model. When SIS is used to repair an experimental ventral abdominal hernia in this model, it is rapidly incorporated into host tissue within 28 days of implantation. Histologically, incorporation of their implanted material into host tissue is characterized by a robust fibrovascular response. Future refinements and applications of the rat abdominal hernia model may likely involve diabetic and/or obese animals as a means to more closely mimic common co-morbidities of man. PMID- 28994801 TI - Sequence-specific and Selective Recognition of Double-stranded RNAs over Single stranded RNAs by Chemically Modified Peptide Nucleic Acids. AB - RNAs are emerging as important biomarkers and therapeutic targets. Thus, there is great potential in developing chemical probes and therapeutic ligands for the recognition of RNA sequence and structure. Chemically modified Peptide Nucleic Acid (PNA) oligomers have been recently developed that can recognize RNA duplexes in a sequence-specific manner. PNAs are chemically stable with a neutral peptide like backbone. PNAs can be synthesized relatively easily by the manual Boc chemistry solid-phase peptide synthesis method. PNAs are purified by reverse phase HPLC, followed by molecular weight characterization by matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF). Non-denaturing polyacrylamide gel electrophoresis (PAGE) technique facilitates the imaging of the triplex formation, because carefully designed free RNA duplex constructs and PNA bound triplexes often show different migration rates. Non-denaturing PAGE with ethidium bromide post staining is often an easy and informative technique for characterizing the binding affinities and specificities of PNA oligomers. Typically, multiple RNA hairpins or duplexes with single base pair mutations can be used to characterize PNA binding properties, such as binding affinities and specificities. 2-Aminopurine is an isomer of adenine (6-aminopurine); the 2 aminopurine fluorescence intensity is sensitive to local structural environment changes, and is suitable for the monitoring of triplex formation with the 2 aminopurine residue incorporated near the PNA binding site. 2-Aminopurine fluorescence titration can also be used to confirm the binding selectivity of modified PNAs towards targeted double-stranded RNAs (dsRNAs) over single-stranded RNAs (ssRNAs). UV-absorbance-detected thermal melting experiments allow the measurement of the thermal stability of PNA-RNA duplexes and PNA.RNA2 triplexes. Here, we describe the synthesis and purification of PNA oligomers incorporating modified residues, and describe biochemical and biophysical methods for characterization of the recognition of RNA duplexes by the modified PNAs. PMID- 28994803 TI - An Experimental Protocol for Assessing the Performance of New Ultrasound Probes Based on CMUT Technology in Application to Brain Imaging. AB - The possibility to perform an early and repeatable assessment of imaging performance is fundamental in the design and development process of new ultrasound (US) probes. Particularly, a more realistic analysis with application specific imaging targets can be extremely valuable to assess the expected performance of US probes in their potential clinical field of application. The experimental protocol presented in this work was purposely designed to provide an application-specific assessment procedure for newly-developed US probe prototypes based on Capacitive Micromachined Ultrasonic Transducer (CMUT) technology in relation to brain imaging. The protocol combines the use of a bovine brain fixed in formalin as the imaging target, which ensures both realism and repeatability of the described procedures, and of neuronavigation techniques borrowed from neurosurgery. The US probe is in fact connected to a motion tracking system which acquires position data and enables the superposition of US images to reference Magnetic Resonance (MR) images of the brain. This provides a means for human experts to perform a visual qualitative assessment of the US probe imaging performance and to compare acquisitions made with different probes. Moreover, the protocol relies on the use of a complete and open research and development system for US image acquisition, i.e. the Ultrasound Advanced Open Platform (ULA-OP) scanner. The manuscript describes in detail the instruments and procedures involved in the protocol, in particular for the calibration, image acquisition and registration of US and MR images. The obtained results prove the effectiveness of the overall protocol presented, which is entirely open (within the limits of the instrumentation involved), repeatable, and covers the entire set of acquisition and processing activities for US images. PMID- 28994804 TI - Biodegradable Magnesium Stent Treatment of Saccular Aneurysms in a Rat Model - Introduction of the Surgical Technique. AB - The steady progess in the armamentarium of techniques available for endovascular treatment of intracranial aneurysms requires affordable and reproducable experimental animal models to test novel embolization materials such as stents and flow diverters. The aim of the present project was to design a safe, fast, and standardized surgical technique for stent assisted embolization of saccular aneurysms in a rat animal model. Saccular aneurysms were created from an arterial graft from the descending aorta.The aneurysms were microsurgically transplanted through end-to-side anastomosis to the infrarenal abdominal aorta of a syngenic male Wistar rat weighing >500 g. Following aneurysm anastomosis, aneurysm embolization was performed using balloon expandable magnesium stents (2.5 mm x 6 mm). The stent system was retrograde introduced from the lower abdominal aorta using a modified Seldinger technique. Following a pilot series of 6 animals, a total of 67 rats were operated according to established standard operating procedures. Mean surgery time, mean anastomosis time, and mean suturing time of the artery puncture site were 167 +/- 22 min, 26 +/- 6 min and 11 +/- 5 min, respectively. The mortality rate was 6% (n=4). The morbidity rate was 7.5% (n=5), and in-stent thrombosis was found in 4 cases (n=2 early, n=2 late in stent thrombosis). The results demonstrate the feasibility of standardized stent occlusion of saccular sidewall aneurysms in rats - with low rates of morbidity and mortality. This stent embolization procedure combines the opportunity to study novel concepts of stent or flow diverter based devices as well as the molecular aspects of healing. PMID- 28994805 TI - Bouncing Ball with a Uniformly Varying Velocity in a Metronome Synchronization Task. AB - Sensorimotor synchronization (SMS), a fundamental human ability to coordinate movements with external rhythms, has long been thought to be modality specific. In the canonical metronome synchronization task that requires tapping a finger along with an isochronous sequence, a well-established finding is that synchronization is much more stable to an auditory sequence consisting of auditory tones than to a visual sequence consisting of visual flashes. However, recent studies have shown that periodically moving visual stimuli can substantially improve synchronization compared with visual flashes. In particular, synchronization of a visual bouncing ball that has a uniformly varying velocity was found to be not less stable than synchronization of auditory tones. Here, the current protocol describes the application of the bouncing ball with a uniformly varying velocity in a metronome synchronization task. The usage of the bouncing ball in sequences with different inter-onset intervals (IOI) is included. The representative results illustrate synchronization performance of the bouncing ball, as compared with the performances of auditory tones and visual flashes. Given its comparable synchronization performance to that of auditory tones, the bouncing ball is of particular importance for addressing the current research topic of whether modality-specific mechanisms underlay SMS. PMID- 28994806 TI - Solubility of Hydrophobic Compounds in Aqueous Solution Using Combinations of Self-assembling Peptide and Amino Acid. AB - Self-assembling peptides (SAPs) are promising vehicles for the delivery of hydrophobic therapeutics for clinical applications; their amphipathic properties allow them to dissolve hydrophobic compounds in the aqueous environment of the human body. However, self-assembling peptide solutions have poor blood compatibility (e.g., low osmolarity), hindering their clinical application through intravenous administrations. We have recently developed a generalized platform for hydrophobic drug delivery, which combines SAPs with amino acid solutions (SAP-AA) to enhance drug solubility and increase formulation osmolarity to reach the requirements for clinical uses. This formulation strategy was thoroughly tested in the context of three structurally different hydrophobic compounds - PP2, rottlerin, and curcumin - in order to demonstrate its versatility. Furthermore, we examined effects of changing formulation components by analyzing 6 different SAPs, 20 naturally existing amino acids at low and high concentrations, and two different co-solvents dimethyl sulfoxide (DMSO) and ethanol. Our strategy proved to be effective in optimizing components for a given hydrophobic drug, and therapeutic function of the formulated inhibitor, PP2, was observed both in vitro and in vivo. This manuscript outlines our generalized formulation method using SAP-AA combinations for hydrophobic compounds, and analysis of solubility as a first step towards potential use of these formulations in more functional studies. We include representative solubility results for formulation of the hydrophobic compound, curcumin, and discuss how our methodology serves as a platform for future biological studies and disease models. PMID- 28994807 TI - Dry Film Photoresist-based Electrochemical Microfluidic Biosensor Platform: Device Fabrication, On-chip Assay Preparation, and System Operation. AB - In recent years, biomarker diagnostics became an indispensable tool for the diagnosis of human disease, especially for the point-of-care diagnostics. An easy to-use and low-cost sensor platform is highly desired to measure various types of analytes (e.g., biomarkers, hormones, and drugs) quantitatively and specifically. For this reason, dry film photoresist technology - enabling cheap, facile, and high-throughput fabrication - was used to manufacture the microfluidic biosensor presented here. Depending on the bioassay used afterwards, the versatile platform is capable of detecting various types of biomolecules. For the fabrication of the device, platinum electrodes are structured on a flexible polyimide (PI) foil in the only clean-room process step. The PI foil serves as a substrate for the electrodes, which are insulated with an epoxy-based photoresist. The microfluidic channel is subsequently generated by the development and lamination of dry film photoresist (DFR) foils onto the PI wafer. By using a hydrophobic stopping barrier in the channel, the channel is separated into two specific areas: an immobilization section for the enzyme-linked assay and an electrochemical measurement cell for the amperometric signal readout. The on-chip bioassay immobilization is performed by the adsorption of the biomolecules to the channel surface. The glucose oxidase enzyme is used as a transducer for electrochemical signal generation. In the presence of the substrate, glucose, hydrogen peroxide is produced, which is detected at the platinum working electrode. The stop-flow technique is applied to obtain signal amplification along with rapid detection. Different biomolecules can quantitatively be measured by means of the introduced microfluidic system, giving an indication of different types of diseases, or, in regard to therapeutic drug monitoring, facilitating a personalized therapy. PMID- 28994808 TI - Study of Siphon Breaker Experiment and Simulation for a Research Reactor. AB - Under the design conditions of a research reactor, the siphon phenomenon induced by pipe rupture can cause continuous outward flow of water. To prevent this outflow, a control device is required. A siphon breaker is a type of safety device that can be utilized to control the loss of coolant water effectively. To analyze the characteristics of siphon breaking, a real-scale experiment was conducted. From the results of the experiment, it was found that there are several design factors that affect the siphon breaking phenomenon. Therefore, there is a need to develop a theoretical model capable of predicting and analyzing the siphon breaking phenomenon under various design conditions. Using the experimental data, it was possible to formulate a theoretical model that accurately predicts the progress and the result of the siphon breaking phenomenon. The established theoretical model is based on fluid mechanics and incorporates the Chisholm model to analyze two-phase flow. From Bernoulli's equation, the velocity, quantity, undershooting height, water level, pressure, friction coefficient, and factors related to the two-phase flow could be obtained or calculated. Moreover, to utilize the model established in this study, a siphon breaker analysis and design program was developed. The simulation program operates on the theoretical model basis and returns the result as a graph. The user can confirm the possibility of the siphon breaking by checking the shape of the graph. Furthermore, saving the entire simulation result is possible and it can be used as a resource for analyzing the real siphon breaking system. In conclusion, the user can confirm the status of the siphon breaking and design the siphon breaker system using the program developed in this study. PMID- 28994809 TI - Sample Preparation for Mass Spectrometry-based Identification of RNA-binding Regions. AB - Noncoding RNAs play important roles in several nuclear processes, including regulating gene expression, chromatin structure, and DNA repair. In most cases, the action of noncoding RNAs is mediated by proteins whose functions are in turn regulated by these interactions with noncoding RNAs. Consistent with this, a growing number of proteins involved in nuclear functions have been reported to bind RNA and in a few cases the RNA-binding regions of these proteins have been mapped, often through laborious, candidate-based methods. Here, we report a detailed protocol to perform a high-throughput, proteome-wide unbiased identification of RNA-binding proteins and their RNA-binding regions. The methodology relies on the incorporation of a photoreactive uridine analog in the cellular RNA, followed by UV-mediated protein-RNA crosslinking, and mass spectrometry analyses to reveal RNA-crosslinked peptides within the proteome. Although we describe the procedure for mouse embryonic stem cells, the protocol should be easily adapted to a variety of cultured cells. PMID- 28994810 TI - Preparation of Chitosan-based Injectable Hydrogels and Its Application in 3D Cell Culture. AB - The protocol presents a facile, efficient, and versatile method to prepare chitosan-based hydrogels using dynamic imine chemistry. The hydrogel is prepared by mixing solutions of glycol chitosan with a synthesized benzaldehyde terminated polymer gelator, and hydrogels are efficiently obtained in several minutes at room temperature. By varying ratios between glycol chitosan, polymer gelator, and water contents, versatile hydrogels with different gelation times and stiffness are obtained. When damaged, the hydrogel can recover its appearances and modulus, due to the reversibility of the dynamic imine bonds as crosslinkages. This self healable property enables the hydrogel to be injectable since it can be self healed from squeezed pieces to an integral bulk hydrogel after the injection process. The hydrogel is also multi-responsive to many bio-active stimuli due to different equilibration statuses of the dynamic imine bonds. This hydrogel was confirmed as bio-compatible, and L929 mouse fibroblast cells were embedded following standard procedures and the cell proliferation was easily assessed by a 3D cell cultivation process. The hydrogel can offer an adjustable platform for different research where a physiological mimic of a 3D environment for cells is profited. Along with its multi-responsive, self-healable, and injectable properties, the hydrogels can potentially be applied as multiple carriers for drugs and cells in future bio-medical applications. PMID- 28994811 TI - Precise, High-throughput Analysis of Bacterial Growth. AB - Bacterial growth is a central concept in the development of modern microbial physiology, as well as in the investigation of cellular dynamics at the systems level. Recent studies have reported correlations between bacterial growth and genome-wide events, such as genome reduction and transcriptome reorganization. Correctly analyzing bacterial growth is crucial for understanding the growth dependent coordination of gene functions and cellular components. Accordingly, the precise quantitative evaluation of bacterial growth in a high-throughput manner is required. Emerging technological developments offer new experimental tools that allow updates of the methods used for studying bacterial growth. The protocol introduced here employs a microplate reader with a highly optimized experimental procedure for the reproducible and precise evaluation of bacterial growth. This protocol was used to evaluate the growth of several previously described Escherichia coli strains. The main steps of the protocol are as follows: the preparation of a large number of cell stocks in small vials for repeated tests with reproducible results, the use of 96-well plates for high throughput growth evaluation, and the manual calculation of two major parameters (i.e., maximal growth rate and population density) representing the growth dynamics. In comparison to the traditional colony-forming unit (CFU) assay, which counts the cells that are cultured in glass tubes over time on agar plates, the present method is more efficient and provides more detailed temporal records of growth changes, but has a stricter detection limit at low population densities. In summary, the described method is advantageous for the precise and reproducible high-throughput analysis of bacterial growth, which can be used to draw conceptual conclusions or to make theoretical observations. PMID- 28994812 TI - The C. elegans Excretory Canal as a Model for Intracellular Lumen Morphogenesis and In Vivo Polarized Membrane Biogenesis in a Single Cell: labeling by GFP fusions, RNAi Interaction Screen and Imaging. AB - The four C. elegans excretory canals are narrow tubes extended through the length of the animal from a single cell, with almost equally far extended intracellular endotubes that build and stabilize the lumen with a membrane and submembraneous cytoskeleton of apical character. The excretory cell expands its length approximately 2,000 times to generate these canals, making this model unique for the in vivo assessment of de novo polarized membrane biogenesis, intracellular lumen morphogenesis and unicellular tubulogenesis. The protocol presented here shows how to combine standard labeling, gain- and loss-of-function genetic or RNA interference (RNAi)-, and microscopic approaches to use this model to visually dissect and functionally analyze these processes on a molecular level. As an example of a labeling approach, the protocol outlines the generation of transgenic animals with fluorescent fusion proteins for live analysis of tubulogenesis. As an example of a genetic approach, it highlights key points of a visual RNAi-based interaction screen designed to modify a gain-of-function cystic canal phenotype. The specific methods described are how to: label and visualize the canals by expressing fluorescent proteins; construct a targeted RNAi library and strategize RNAi screening for the molecular analysis of canal morphogenesis; visually assess modifications of canal phenotypes; score them by dissecting fluorescence microscopy; characterize subcellular canal components at higher resolution by confocal microscopy; and quantify visual parameters. The approach is useful for the investigator who is interested in taking advantage of the C. elegans excretory canal for identifying and characterizing genes involved in the phylogenetically conserved processes of intracellular lumen and unicellular tube morphogenesis. PMID- 28994813 TI - A Primary Human Trophoblast Model to Study the Effect of Inflammation Associated with Maternal Obesity on Regulation of Autophagy in the Placenta. AB - Maternal obesity is associated with an increased risk of adverse perinatal outcomes that are likely mediated by compromised placental function that can be attributed to, in part, the dysregulation of autophagy. Aberrant changes in the expression of autophagy regulators in the placentas from obese pregnancies may be regulated by inflammatory processes associated with both obesity and pregnancy. Described here is a protocol for sampling of villous tissue and isolation of villous cytotrophoblasts from the term human placenta for primary cell culture. This is followed by a method for simulating the inflammatory milieu in the obese intrauterine environment by treating primary trophoblasts from lean pregnancies with tumor necrosis factor alpha (TNFalpha), a proinflammatory cytokine that is elevated in obesity and in pregnancy. Through the implementation of the protocol described here, it is found that exposure to exogenous TNFalpha regulates the expression of Rubicon, a negative regulator of autophagy, in trophoblasts from lean pregnancies with female fetuses. While a variety of biological factors in the obese intrauterine environment maintain the potential to modulate critical pathways in trophoblasts, this ex vivo system is especially useful for determining if expression patterns observed in vivo in human placentas with maternal obesity are a direct result of TNFalpha signaling. Ultimately, this approach affords the opportunity to parse out the regulatory and molecular implications of inflammation associated with maternal obesity on autophagy and other critical cellular pathways in trophoblasts that have the potential to impact placental function. PMID- 28994814 TI - Real-time Quaking-induced Conversion Assay for Detection of CWD Prions in Fecal Material. AB - The RT-QuIC technique is a sensitive in vitro cell-free prion amplification assay based mainly on the seeded misfolding and aggregation of recombinant prion protein (PrP) substrate using prion seeds as a template for the conversion. RT QuIC is a novel high-throughput technique which is analogous to real-time polymerase chain reaction (PCR). Detection of amyloid fibril growth is based on the dye Thioflavin T, which fluoresces upon specific interaction with ?-sheet rich proteins. Thus, amyloid formation can be detected in real time. We attempted to develop a reliable non-invasive screening test to detect chronic wasting disease (CWD) prions in fecal extract. Here, we have specifically adapted the RT QuIC technique to reveal PrPSc seeding activity in feces of CWD infected cervids. Initially, the seeding activity of the fecal extracts we prepared was relatively low in RT-QuIC, possibly due to potential assay inhibitors in the fecal material. To improve seeding activity of feces extracts and remove potential assay inhibitors, we homogenized the fecal samples in a buffer containing detergents and protease inhibitors. We also submitted the samples to different methodologies to concentrate PrPSc on the basis of protein precipitation using sodium phosphotungstic acid, and centrifugal force. Finally, the feces extracts were tested by optimized RT-QuIC which included substrate replacement in the protocol to improve the sensitivity of detection. Thus, we established a protocol for sensitive detection of CWD prion seeding activity in feces of pre-clinical and clinical cervids by RT-QuIC, which can be a practical tool for non-invasive CWD diagnosis. PMID- 28994815 TI - In Vitro Characterization of the Electrophysiological Properties of Colonic Afferent Fibers in Rats. AB - Dysfunction of the colonic sensory nerves has been implicated in the pathophysiology of several common conditions, including functional and inflammatory bowel diseases and diabetes. Here, we describe a protocol for the in vitro characterization of the electrophysiological properties of colonic afferents in rats. The colorectum, with the intact pelvic ganglion (PG) attached, is removed from the rat; superfused with carbogenated Krebs solution in the recording chamber; and cannulated at the oral and anal ends to allow for distension. A fine nerve bundle emanating from the PG is identified, and the multiunit afferent nerve activity is recorded using a suction electrode. Distension of the colonic segment elicits gradual increases in multiunit discharge. A principal component analysis is conducted to differentiate the low threshold, the high-threshold, and the wide-dynamic range afferent fibers. Chemical sensitivity of colonic afferents can be studied through the bath or intraluminal administration of test compounds. This protocol can be modified for application to other species, such as mice and guinea pigs, and to study the differences in the electrophysiological properties of thoracolumbar/hypogastric and lumbosacral/pelvic afferents of the descending colon in normal and pathological conditions. PMID- 28994816 TI - The Aortic Ring Co-culture Assay: A Convenient Tool to Assess the Angiogenic Potential of Mesenchymal Stromal Cells In Vitro. AB - Angiogenesis is a complex, highly regulated process responsible for providing and maintaining adequate tissue perfusion. Insufficient vasculature maintenance and pathological malformations can result in severe ischemic diseases, while overly abundant vascular development is associated with cancer and inflammatory disorders. A promising form of pro-angiogenic therapy is the use of angiogenic cell sources, which can provide regulatory factors as well as physical support for newly developing vasculature. Mesenchymal Stromal Cells (MSCs) are extensively investigated candidates for vascular regeneration due to their paracrine effects and their ability to detect and home to ischemic or inflamed tissues. In particular, first trimester human umbilical cord perivascular cells (FTM HUCPVCs) are a highly promising candidate due to their pericyte-like properties, high proliferative and multilineage potential, immune-privileged properties, and robust paracrine profile. To effectively evaluate potentially angiogenic regenerative cells, it is a requisite to test them in reliable and "translatable" pre-clinical assays. The aortic ring assay is an ex vivo angiogenesis model that allows for easy quantification of tubular endothelial structures, provides accessory supportive cells and extracellular matrix (ECM) from the host, excludes inflammatory components, and is fast and inexpensive to set up. This is advantageous when compared to in vivo models (e.g., corneal assay, Matrigel plug assay); the aortic ring assay can track the administered cells and observe intercellular interactions while avoiding xeno-immune rejection. We present a protocol for a novel application of the aortic ring assay, which includes human MSCs in co-cultures with developing rat aortic endothelial networks. This assay allows for the analysis of the MSC contribution to tube formation and development through physical pericyte-like interactions and of their potency for actively migrating to sites of angiogenesis, and for evaluating their ability to perform and mediate ECM processing. This protocol provides further information on changes in MSC phenotype and gene expression following co-culture. PMID- 28994817 TI - A Simple, Robust, and High Throughput Single Molecule Flow Stretching Assay Implementation for Studying Transport of Molecules Along DNA. AB - We describe a simple, robust and high throughput single molecule flow-stretching assay for studying 1D diffusion of molecules along DNA. In this assay, glass coverslips are functionalized in a one-step reaction with silane-PEG-biotin. Flow cells are constructed by sandwiching an adhesive tape with pre-cut channels between a functionalized coverslip and a PDMS slab containing inlet and outlet holes. Multiple channels are integrated into one flow cell and the flow of reagents into each channel can be fully automated, which significantly increases the assay throughput and reduces hands-on time per assay. Inside each channel, biotin-lambda-DNAs are immobilized on the surface and a laminar flow is applied to flow-stretch the DNAs. The DNA molecules are stretched to >80% of their contour length and serve as spatially extended templates for studying the binding and transport activity of fluorescently labeled molecules. The trajectories of single molecules are tracked by time-lapse Total Internal Reflection Fluorescence (TIRF) imaging. Raw images are analyzed using streamlined custom single particle tracking software to automatically identify trajectories of single molecules diffusing along DNA and estimate their 1D diffusion constants. PMID- 28994818 TI - Live-cell Measurement of Odorant Receptor Activation Using a Real-time cAMP Assay. AB - The enormous sizes of the mammalian odorant receptor (OR) families present difficulties to find their cognate ligands among numerous volatile chemicals. To efficiently and accurately deorphanize ORs, we combine the use of a heterologous cell line to express mammalian ORs and a genetically modified biosensor plasmid to measure cAMP production downstream of OR activation in real time. This assay can be used to screen odorants against ORs and vice versa. Positive odorant receptor interactions from the screens can be subsequently confirmed by testing against various odor concentrations, generating concentration-response curves. Here we used this method to perform a high-throughput screening of an odorous compound against a human OR library expressed in Hana3A cells and confirmed that the positively-responding receptor is the cognate receptor for the compound of interest. We found this high-throughput detection method to be efficient and reliable in assessing OR activation and our data provide an example of its potential use in OR functional studies. PMID- 28994819 TI - Building a locally diploid genome and transcriptome of the diatom Fragilariopsis cylindrus. AB - The genome of the cold-adapted diatom Fragilariopsis cylindrus is characterized by highly diverged haplotypes that intersperse its homozygous genome. Here, we describe how a combination of PacBio DNA and Illumina RNA sequencing can be used to resolve this complex genomic landscape locally into the highly diverged haplotypes, and how to map various environmentally controlled transcripts onto individual haplotypes. We assembled PacBio sequence data with the FALCON assembler and created a haplotype resolved annotation of the assembly using annotations of a Sanger sequenced F. cylindrus genome. RNA-seq datasets from six different growth conditions were used to resolve allele-specifc gene expression in F. cylindrus. This approach enables to study differential expression of alleles in a complex genomic landscape and provides a useful tool to study how diverged haplotypes in diploid organisms are used for adaptation and evolution to highly variable environments. PMID- 28994821 TI - Chemical, microbial and antibiotic susceptibility analyses of groundwater after a major flood event in Chennai. AB - During floods, human exposure to pathogens through contaminated water leads to the outbreak of epidemic diseases. This research presents the first extensive assessment of surface and groundwater samples collected immediately after a flood (December 2015) and post-flood (April 2016) from the Adyar River of Chennai, a major city in India, for major ions, trace metals, bacterial population, and pathogens. Severe rains in a short period of time resulted in flooding which inundated the wells, allowing the entry of sewage contaminated river water into the groundwater zone. This has led to bacterial counts and chemical ions exceeding Bureau of Indian Standard's recommended limits in most flood affected areas. Pathogens isolated from the groundwater showed resistance to antibiotics, namely ceftriaxone, doxycycline and nalidixic acid. However, they were sensitive to chloramphenicol, ciprofloxacin, norfloxacin, and tetracycline. Determining the antibiotic susceptibility of pathogens will help in the treatment of humans affected by contaminated water through an appropriate selection of prescribed medication. PMID- 28994823 TI - A multilayer network dataset of interaction and influence spreading in a virtual world. AB - Presented data contains the record of five spreading campaigns that occurred in a virtual world platform. Users distributed avatars between each other during the campaigns. The processes varied in time and range and were either incentivized or not incentivized. Campaign data is accompanied by events. The data can be used to build a multilayer network to place the campaigns in a wider context. To the best of the authors' knowledge, the study is the first publicly available dataset containing a complete real multilayer social network together, along with five complete spreading processes in it. PMID- 28994822 TI - Whole genome DNA methylation sequencing of the chicken retina, cornea and brain. AB - Whole genome bisulfite sequencing (WGBS) analysis of DNA methylation uses massively parallel next generation sequencing technology to characterize global epigenetic patterns and fluctuations throughout a range of tissue samples. Development of the vertebrate retina is thought to involve extensive epigenetic reprogramming during embryogenesis. The chicken embryo (Gallus gallus) is a classic model system for studying developmental biology and retinogenesis, however, there are currently no publicly available data sets describing the developing chicken retinal methylome. Here we used Illumina WGBS analysis to characterize genome-wide patterns of DNA methylation in the developing chicken retina as well as cornea and brain in an effort to further our understanding of retina-specific epigenetic regulation. These data will be valuable to the vision research community for correlating global changes in DNA methylation to differential gene expression between ocular and neural tissues during critical developmental time points of retinogenesis in the chicken retina. PMID- 28994820 TI - Sexual dimorphism of AMBRA1-related autistic features in human and mouse. AB - Ambra1 is linked to autophagy and neurodevelopment. Heterozygous Ambra1 deficiency induces autism-like behavior in a sexually dimorphic manner. Extraordinarily, autistic features are seen in female mice only, combined with stronger Ambra1 protein reduction in brain compared to males. However, significance of AMBRA1 for autistic phenotypes in humans and, apart from behavior, for other autism-typical features, namely early brain enlargement or increased seizure propensity, has remained unexplored. Here we show in two independent human samples that a single normal AMBRA1 genotype, the intronic SNP rs3802890-AA, is associated with autistic features in women, who also display lower AMBRA1 mRNA expression in peripheral blood mononuclear cells relative to female GG carriers. Located within a non-coding RNA, likely relevant for mRNA and protein interaction, rs3802890 (A versus G allele) may affect its stability through modification of folding, as predicted by in silico analysis. Searching for further autism-relevant characteristics in Ambra1+/- mice, we observe reduced interest of female but not male mutants regarding pheromone signals of the respective other gender in the social intellicage set-up. Moreover, altered pentylentetrazol-induced seizure propensity, an in vivo readout of neuronal excitation-inhibition dysbalance, becomes obvious exclusively in female mutants. Magnetic resonance imaging reveals mild prepubertal brain enlargement in both genders, uncoupling enhanced brain dimensions from the primarily female expression of all other autistic phenotypes investigated here. These data support a role of AMBRA1/Ambra1 partial loss-of-function genotypes for female autistic traits. Moreover, they suggest Ambra1 heterozygous mice as a novel multifaceted and construct-valid genetic mouse model for female autism. PMID- 28994826 TI - Kidney cancer: Combination of HDAC inhibitor with IL-2 promising. PMID- 28994824 TI - Single cell genomics of uncultured marine alveolates shows paraphyly of basal dinoflagellates. AB - Marine alveolates (MALVs) are diverse and widespread early-branching dinoflagellates, but most knowledge of the group comes from a few cultured species that are generally not abundant in natural samples, or from diversity analyses of PCR-based environmental SSU rRNA gene sequences. To more broadly examine MALV genomes, we generated single cell genome sequences from seven individually isolated cells. Genes expected of heterotrophic eukaryotes were found, with interesting exceptions like presence of proteorhodopsin and vacuolar H+-pyrophosphatase. Phylogenetic analysis of concatenated SSU and LSU rRNA gene sequences provided strong support for the paraphyly of MALV lineages. Dinoflagellate viral nucleoproteins were found only in MALV groups that branched as sister to dinokaryotes. Our findings indicate that multiple independent origins of several characteristics early in dinoflagellate evolution, such as a parasitic life style, underlie the environmental diversity of MALVs, and suggest they have more varied trophic modes than previously thought. PMID- 28994827 TI - Bladder cancer: Mastering the immune microenvironment. PMID- 28994825 TI - Clustergrammer, a web-based heatmap visualization and analysis tool for high dimensional biological data. AB - Most tools developed to visualize hierarchically clustered heatmaps generate static images. Clustergrammer is a web-based visualization tool with interactive features such as: zooming, panning, filtering, reordering, sharing, performing enrichment analysis, and providing dynamic gene annotations. Clustergrammer can be used to generate shareable interactive visualizations by uploading a data table to a web-site, or by embedding Clustergrammer in Jupyter Notebooks. The Clustergrammer core libraries can also be used as a toolkit by developers to generate visualizations within their own applications. Clustergrammer is demonstrated using gene expression data from the cancer cell line encyclopedia (CCLE), original post-translational modification data collected from lung cancer cells lines by a mass spectrometry approach, and original cytometry by time of flight (CyTOF) single-cell proteomics data from blood. Clustergrammer enables producing interactive web based visualizations for the analysis of diverse biological data. PMID- 28994828 TI - Prostate cancer: Potential biomarkers of aggressive disease. PMID- 28994829 TI - Bladder cancer: Benefit of adjuvant chemotherapy in UTUC unclear. PMID- 28994830 TI - Surgery: Enhanced recovery after cystectomy: cocktails, culture, or consistency? PMID- 28994831 TI - Bladder cancer: Combination therapy effective in advanced disease. PMID- 28994832 TI - Carotid endarterectomy for treatment of carotid in-stent restenosis: long-term follow-up results and surgery experiences from one single centre. AB - OBJECTIVE: Few studies have reported the surgical treatment of carotid in-stent restenosis (ISR), more data and longer follow-up are needed. We describe the surgical treatment of ISR by standard carotid endarterectomy (CEA) with stent removal, including long-term follow-up in 10 patients from our centre. METHODS: Ten patients from our centre who underwent CEA with stent removal for ISR were retrospectively analysed, including nine symptomatic and one asymptomatic ISR of at least 70% with mean age 67.3, the median time between carotid artery stenting and CEA was 17 months (range, 2-54 months). RESULTS: Standard CEA with stent removal was performed in all 10 patients without much technical difficulty (9 male and 1 female, mean age 67.3). Two cases were performed in hybrid operation room. There were a total of three complications that happened in three patients (30%) respectively. An asymptomatic dissecting aneurysm was formed on the petrous internal carotid artery in one patient who was followed up without intervention. In the second case, dissection occurred in the arterial wall distal to the site of the stent after stent removal revealed by intraoperative angiography, and another stent was implanted. The patient sustained temporary hypoglossal nerve dysfunction postoperatively. The third patient suffered cerebral hyperperfusion with complete recovery when discharged. No neurological complications occurred in other seven patients. After follow-up of 25 months (range, 11-54 months), one patient died of rectal cancer without ischaemic attack and restenosis 4 years postoperation; in one patient occurred recurrent symptomatic restenosis (90%) 1 year later; all other patients remained asymptomatic and without recurrent restenosis (>50%) by follow-up carotid ultrasound or CT angiography. CONCLUSION: It seems that CEA with stent removal is a reasonable choice, by experienced hand, for symptomatic ISR with higher but acceptable complications. The indication of stent removal for asymptomatic ISR needs further observation. PMID- 28994834 TI - Insights into the mechanism of ethanol synthesis and ethyl acetate inhibition from acetic acid hydrogenation over Cu2In(100): a DFT study. AB - Developing low-cost and high-efficiency non-noble metal catalysts is beneficial for industrially massive synthesis of ethanol from acetic acid, which can be obtained from renewable biomass. Understanding the detailed mechanism of the reaction from a molecular level provides insights that can be used to tailor catalysts to improve their performance. In this study, alternative mechanisms for ethanol synthesis from acetic acid hydrogenation over Cu2In(100) have been investigated using periodic density functional theory (DFT) calculations. The pathway of CH3COOH -> CH3COO -> CH3CHOO -> CH3CHO -> CH3CH2O -> CH3CH2OH was found to be most favorable. The high activation barriers for CH3COO hydrogenation to CH3CHOO (1.33 eV) and CH3CH2O hydrogenation to CH3CH2OH (1.04 eV) indicate that these two steps are the rate-limiting steps. In addition, the results also show that there are probably two more active intermediate species of CH3CO and CH3CH(OH)O besides CH3COO. Furthermore, the synergy and the role of copper and indium in the Cu-In bimetallic catalyst were discussed. The adsorption strength of copper will be improved by indium. Indium, however, has high chemical inertness in Cu2In. They evenly divided the surface into small reaction areas which could significantly inhibit ethyl acetate formation through the hindrance effect. PMID- 28994833 TI - The efficacy and safety of endovascular recanalization of occluded large cerebral arteries during the subacute phase of cerebral infarction: a case series report. AB - BACKGROUND: Intravenous tissue plasminogen activator with or without mechanical thrombectomy during the acute phase are approved therapies for ischaemic stroke. Due to the short treatment time window (<6 hours) and often treatment failure, these patients would still have an intracranial arterial occlusion (IAO). It is unclear whether these patients can benefit from subsequent interventional recanalizationof their occluded artery in the subacute phase. In this retrospective study, we have examined the efficacy and safety in patients who have received either percutaneous transluminal angioplasty (PTA) or percutaneous transluminal angioplasty and stenting (PTAS) for IAO in the subacute phase of their stroke. METHODS: Patients with subacute symptomatic ischaemic stroke caused by IAO were assessed to identify the responsible artery and low perfusion areas by CT angiography, MR angiography or digital subtraction angiography. In eligible patients, a PTA or PTAS was performed to reopen the occluded artery. Regular antithrombotic therapy, use of statins, control of risk factors and rehabilitation therapy were prescribed after the procedure. All patients had regular follow-up up to 12 months. RESULTS: PTA or PTAS was performed in 16 patients with cerebral infarction caused by IAO in the subacute phase. After the procedure, 12 cases were recanalized, two were partially recanalized and two failed to open. One patient with left C6 segment occlusion of the carotid artery had a central retinal artery embolism after PTAS. The perioperative adverse events were 6.25%. At 3 months, the distribution of modified Rankin scale scores was 0 (seven cases), 1 (three cases), 2 (five cases) and 3 (one case). CONCLUSION: Selective PTA or PTAS could be performed in ischaemic stroke patients with a small infarct size and large area of hypoperfusion from an occluded large cerebral artery after the acute phase. It may improve neurological dysfunction and reduce the incidence of disability. PMID- 28994835 TI - Attractive PHHP interactions revealed by state-of-the-art ab initio calculations. AB - We report in this work a combined structural and state-of-the-art computational study of homopolar P-HH-P intermolecular contacts. Database surveys have shown the abundance of such surprisingly unexplored contacts, which are usually accompanied by other weak interactions in the solid state. By means of a detailed theoretical study utilizing SAPT(DFT), MP2, SCS-MP2, MP2C and CCSD(T) methods and both aug-cc-pVXZ and aug-cc-pCVXZ (X = D, T, Q, 5) basis sets as well as extrapolation to the CBS limit, we have shown that P-HH-P contacts are indeed attractive and considerably strong. SAPT(DFT) calculations have revealed the dispersive nature of the P-HH-P interaction with only minor contribution of the inductive term, whereas the first-order electrostatic term is clearly overbalanced by the first-order exchange energy. In general the computed interaction energies follow the trend: E ~ E < E < E. Our results have also shown that the aug-cc-pVDZ (or aug-cc-pCVDZ) basis set is not yet well balanced and that the second-order dispersion energy term is the slowest converging among all SAPT(DFT) energy components. Compared to aug-cc-pVXZ basis sets, their core correlation counterparts have a modest influence on all supermolecular interaction energies and a negligible influence on both the SAPT(DFT) interaction energy and its components. PMID- 28994836 TI - Confined water dynamics in a hydrated photosynthetic pigment-protein complex. AB - Water is of fundamental importance for life. It plays a critical role in all biological systems. In phycocyanin, a pigment-protein complex, the hydration level influences its absorption spectrum. However, there is currently a gap in the understanding of how protein interfaces affect water's structure and properties. This work presents combined dielectric and calorimetric measurements of hydrated phycocyanin with different levels of hydration in a broad temperature interval. Based on the dielectric and calorimetric tests, it was shown that two types of water exist in the phycocyanin hydration shell. One is confined water localized inside the phycocyanin ring and the second is the water that is embedded in the protein structure and participates in the protein solvation. The water confined in the phycocyanin ring melts at the temperature 195 +/- 3 K and plays a role in the solvation at higher temperatures. Moreover, the dynamics of all types of water was found to be effected by the presence of the ionic buffer. PMID- 28994837 TI - Size-dependent Raman shift of semiconductor nanomaterials determined using bond number and strength. AB - Significant variations in Raman shifts with decreasing material size, D, have been detected in Raman spectroscopy. In this study, we propose a simple and unified model to determine and explain the size-dependent Raman shift, omega(D), of low-dimensional semiconductor nanomaterials. omega(D) was found to be a function of bond number in a system, with an obvious decline in Raman shift observed when size dropped to the nanoscale. This arose from a decrease in coordination number, Z(D), and increase in single bond strength, epsilon(D). The predicted results show good agreement with experimental data for a series of semiconductor nanomaterials, showing that bond number can be used to calculate Raman shifts of nanomaterials. Moreover, this theoretical model was successfully applied to both single crystals and some binary semiconductor nanomaterials. Furthermore, bond number, which is directly related to the nanomaterial shape and size, becomes the only parameter required to determine omega(D) in this model, as both Z(D) and epsilon(D) can be determined from the bond number. This indicates that the established model has the potential to determine Raman shifts of nanomaterials with different shapes and sizes. PMID- 28994838 TI - DFT investigation of the interaction between single-walled carbon nanotubes and fluorene-based conjugated oligomers. AB - pi-Conjugated oligomers with relatively short molecular backbones can be used effectively in dispersion of carbon nanotubes (CNTs). In this paper, we present a systematic study on interactions between diphenylene-fluorene oligomers (DPFs) and single-walled CNTs (SWCNTs) using density functional theory (DFT) calculations. Four DFT methods are used in this work: the long range (LR) corrected CAM-B3LYP, the dispersion (D)-corrected B97D, the LR- and D-corrected wB97XD, and the hybrid B3LYP. The DPFs examined in this study contain different functional groups attached to the pi-conjugated backbone, including two different end groups, carboxaldehyde (ALD) and dithiafulvenyl (DTF), and three different side chains (SCs), C8H17, OC10H21, and SC10H21. The computational results disclose the effects of end groups, SCs, and DFT methods on structures, dipole moments, and energetics of isolated DPFs and DPF/SWCNT combinations. Consistent with our previous study (involving oligo(p-phenylene ethynylene)s (OPEs)) [Aljohani et al., J. Phys. Chem. C, 2017, 121, 4692-4702], our results herein demonstrate that the type of end group plays a key role in determining the strength of interactions between SWNTs and conjugated oligomers. In particular, DTF-endcapped oligomers have a stronger electrostatic interaction with SWCNT than ALD-endcapped oligomers do. As a result, DTF-endcapped conjugated oligomers become more polarized than ALD-endcapped oligomers after complexing with SWCNTs. The magnitude of binding energy, on the other hand, shows dependence on the orientation of the backbone and side chains of these oligomers relative to the SWCNT which in the case of fluorene-based oligomers is not always favourable for optimal binding. This study indicates that fluorene-based oligomers might not be as good dispersants of SWCNTs as OPEs. PMID- 28994839 TI - Feasibility of using microencapsulated phase change materials as filler for improving low temperature performance of rubber sealing materials. AB - The feasibility of a novel composite rubber sealing material to improve sealing under transient cooling (in a so-called blowdown scenario) is investigated here. A composite of hydrogenated nitrile butadiene rubber (HNBR) filled with Micro Encapsulated Phase Change Materials (MEPCM) is described. The fillers contain phase change materials that release heat during the phase transformation from liquid to solid while cooling. This exotherm locally heats the rubber and may improve the function of the seal during a blowdown event. A representative HNBR MEPCM composite was made and the critical thermal and mechanical properties were obtained by simulating the temperature distribution during a blowdown event. Simulations predict that the MEPCM composites can delay the temperature decrease in a region of the seal during the transient blowdown. A sensitivity analysis of material properties is also presented which highlights possible avenues of improvement of the MEPCMs for sealing applications. PMID- 28994840 TI - Silica nanowire assemblies as three-dimensional, optically transparent platforms for constructing highly active SERS substrates. AB - Three-dimensional surface-enhanced Raman scattering (SERS) substrates are prepared via the in situ deposition of silver nanoparticles (AgNPs) on silica nanowire (SiO2 NW) assemblies, either in a free-standing membrane structure or as an optically transparent film supported on Scotch tape. The negatively charged surface of the SiO2 NW favors Ag+ ion enrichment around itself, with the ions forming densely deposited AgNPs on the NW after reducing agents are added to the solution. A SERS substrate with high sensitivity is achieved owing to abundant "hot spots" generated by the inter-AgNP gaps in the 3D geometry of the NW networks. The AgNP-deposited SiO2 NW membrane has a SERS enhancement factor of 2.9 * 108 and a detection limit of 10-9 M towards 4-mercaptopyridine probing and 10-8 M towards dithiocarbamate pesticide (i.e., thiram) probing. Moreover, the AgNP-deposited, Scotch tape-supported SiO2 NW film achieves non-invasive, direct detection of real-world surfaces due to its high sensitivity, high flexibility and optically transparent properties. PMID- 28994841 TI - Phthalocyanine-based coordination polymer nanoparticles for enhanced photodynamic therapy. AB - In the photodynamic therapy (PDT) of cancer, zinc phthalocyanine (ZnPc) as a photosensitizer possesses superior photosensitive properties. However, the therapeutic effect of ZnPc in PDT is limited due to its aggregation, low solubility and poor selectivity. In this study, charge-reversal phthalocyanine based coordination polymer nanoparticles (PCPN) are developed for improving the curative effect of ZnPc. Tetra(4-carboxyphenoxy)-phthalocyaninatozinc(ii) (TPZnPc) is coordinated with the zinc ion to form the core of PCPN, which is coated with a lipid bilayer by self-assembly (PCPNs@Lip). TPZnPc molecules in the core of PCPN are in the monomeric state and can generate cytotoxic singlet oxygen (1O2) efficiently, which solves the solubility and aggregation problems of ZnPc. Meanwhile, 1,2-dicarboxylic-cyclohexane anhydride modified lysyl-cholesterol (DLC) is functionalized on the surface of PCPN (PCPNs@Lip/DLC), endowing PCPN with a charge-reversal ability which could be triggered by a mildly acidic tumor microenvironment. PCPNs@Lip/DLC is proved to enhance tumor cellular uptake and generate more intracellular 1O2 after irradiation. As confirmed by in vitro and in vivo studies, PCPNs@Lip/DLC remarkably increases the PDT effect. All these results demonstrate that PCPNs@Lip/DLC is a promising nanoplatform for the application of ZnPc in effective PDT. PMID- 28994842 TI - Preparation of Bi2S3/carbon quantum dot hybrid materials with enhanced photocatalytic properties under ultraviolet-, visible- and near infrared irradiation. AB - To solve the growing pollution issues, it is a promising alternative to develop efficient sunlight-driven photocatalysts for purifying organic wastewater. Herein, we report a new and efficient full-spectrum-responsive photocatalyst composed of Bi2S3 nanotubes incorporated with carbon quantum dots (C-dots) for rapidly degrading methylene blue (MB) and tetracycline hydrochloride (TC). Compared with naked Bi2S3 nanotubes, the as-prepared Bi2S3/C-dot nanohybrids show a remarkably higher photocatalytic efficiency for degrading MB or TC under ultraviolet (UV-), visible (vis-) and near-infrared (NIR-) light irradiation within 5 minutes. A possible mechanism is proposed for the enhanced photocatalytic activity of the Bi2S3/C-dot nanohybrids. A lower band gap as well as a wider absorbance in the UV-, vis- and NIR-regions can increase the light harvesting ability of the Bi2S3/C-dots. Meanwhile, the existence of C-dots can facilitate the charge separation of the photo-generated electron/hole pairs while electrons transfer from Bi2S3 to C-dots. Besides, an increased surface area of the Bi2S3/C-dot nanohybrids also contributes to the excellent photocatalytic activity. PMID- 28994844 TI - Ru-Catalysed synthesis of fused heterocycle-pyridinones and -pyrones. AB - The synthesis of fused heterocycle-pyridinones has been achieved by oxidative coupling of N-unprotected primary heterocycle-amides with internal alkynes. The reaction, which is catalysed by Ru(ii) and assisted by Cu(ii), takes place through C-H and N-H bond activation of the heterocyclic unit. The scope of the reaction includes a variety of alkynes, electron-rich thiophenes, furans and pyrroles, and even electron-poor pyridines. The reaction is fully regioselective with respect to the position of the C-H bond activation due to the directing effect of the amide group. In the same way, the synthesis of fused heterocycle pyrones (isocoumarins) has been developed by Ru-catalysed oxidative coupling of heterocyclic carboxylic acids and internal alkynes. The reaction involves C-H and O-H bond activation. This reaction also has a broad scope, from electron-rich thiophenes, furans and pyrroles to electron-deficient pyridines and quinolines. PMID- 28994845 TI - Continuous fabrication of a MnS/Co nanofibrous air electrode for wide integration of rechargeable zinc-air batteries. AB - Exploring highly efficient bifunctional electrocatalysts toward the oxygen reduction and evolution reactions is essential for the realization of high performance rechargeable zinc-air batteries. Herein, a novel nanofibrous bifunctional electrocatalyst film, consisting of metallic manganese sulfide and cobalt encapsulated by nitrogen-doped carbon nanofibers (CMS/NCNF), is prepared through a continuous electrospinning method followed by carbonization treatment. The CMS/NCNF bifunctional catalyst shows both comparable ORR and OER performances to those of commercial precious metal-based catalysts. Furthermore, the free standing CMS/NCNF fibrous thin film is directly used as the air electrode in a solid-state zinc-air battery, which exhibits superior flexibility while retaining stable battery performance at different bending angles. This study provides a versatile design route for the rational design of free-standing bifunctional catalysts for direct use as the air electrode in rechargeable zinc-air batteries. PMID- 28994846 TI - 3D self-assembly of ultrafine molybdenum carbide confined in N-doped carbon nanosheets for efficient hydrogen production. AB - Electrochemical water splitting has been intensively pursued as a promising approach to produce clean and sustainable hydrogen fuel. However, the lack of low cost and high-performance electrocatalysts for the hydrogen evolution reaction (HER) hinders the large-scale application. Herein, we have rationally designed and synthesized 3D self-assembly architectures assembled from ultrafine MoC nanoparticles (0D) uniformly embedded within N-doped carbon nanosheets (2D) for the HER via a simple protocol. The well-organized 3D nanostructures are composed of very small MoC nanocrystallites (<2 nm) and free-stretching conductive carbon nanosheets with high specific surface areas and abundant mesopores, which can expose more active sites and facilitate electron/ion transport pathways. Based on the merits of the composition and configuration, the resultant hierarchical 3D self-assembly architectures exhibit remarkable electrocatalytic performance and stability for the HER. PMID- 28994847 TI - One-step synthesis of SnCo nanoconfined in hierarchical carbon nanostructures for lithium ion battery anode. AB - A new strategy for the one-step synthesis of a 0D SnCo nanoparticles-1D carbon nanotubes-3D hollow carbon submicrocube cluster (denoted as SnCo@CNT-3DC) hierarchical nanostructured material was developed via a simple chemical vapor deposition (CVD) process with the assistance of a water-soluble salt (NaCl). The adopted NaCl not only acted as a cubic template for inducing the formation of the 3D hollow carbon submicrocube cluster but also provides a substrate for the SnCo catalysts impregnation and CNT growth, ultimately leading to the successful construction of the unique 0D-1D-3D structured SnCo@CNT-3DC during the CVD of C2H2. When utilized as a lithium-ion battery anode, the SnCo@CNT-3DC composite electrode demonstrated an excellent rate performance and cycling stability for Li ion storage. Specifically, an impressive reversible capacity of 826 mA h g-1 after 100 cycles at 0.1 A g-1 and a high rate capacity of 278 mA h g-1 even after 1000 cycles at 5 A g-1 were achieved. This remarkable electrochemical performance could be ascribed to the unique hierarchical nanostructure of SnCo@CNT-3DC, which guarantees a deep permeation of electrolytes and a shortened lithium salt diffusion pathway in the solid phase as well as numerous hyperchannels for electron transfer. PMID- 28994849 TI - Unexpected formation of gold nanoflowers by a green synthesis method as agents for a safe and effective photothermal therapy. AB - Star fruit (Averrhoa carambola) juice rich in vitamin C and polyphenolic antioxidants was used to synthesize branched gold nanoflowers. These biocompatible and stable gold nanoflowers show strong near-infrared absorption. They are successfully demonstrated to be highly efficient for both in vitro and in vivo photothermal therapy by using an 808 nm laser. PMID- 28994852 TI - ? AB - High dose insulin euglycemia therapy - an important addition to the treatment arsenal in severe toxic myocardial depression Fifty-nine patients who developed hemodynamic symptoms necessitating treatment with vasopressors or inotropes after poisoning with calcium channel blockers (CCB) and beta blockers (BB) between January 2010 and August 2016 were identified by a search of the Poisons Information Centre database. In-hospital circulatory arrest occurred in 16/59 (27 %) and the mortality rate was 7/59 (12 %). Two cases of analytically confirmed combined BB and CCB poisoning were treated with high dose insulin therapy (HIE) and are presented in detail. The outcome in both cases was good. They were the only cases in the study population treated with HIE, although signs of cardiac dysfunction was present in 55/59 (93%) and in all cases of circulatory arrest. Animal studies and international clinical cases indicate that HIE is a safe and effective method to improve cardiac function in CCB and BB poisoning, and its implementation in Sweden may improve the outcome for this at risk population. PMID- 28994853 TI - ? AB - Acute occlusion of the left circumflex coronary artery - in the "blind spot" of the ECG? Acute coronary artery occlusion should be treated with urgent revascularization. ECG is important in the triage of patients with acute coronary syndrome. ST deviation depends on the relation between the location of the transmural ischemia and the positive poles of the 12 ECG leads. In acute occlusion of the left circumflex artery, ST elevation in two contiguous leads is not always present. Instead, isolated ST depression in leads V1-V3 may be present and represents a "STEMI-equivalent" pattern. Detection of acute occlusion of the left circumflex artery may be improved either by including inverted leads or by recording from electrodes on the posterior thorax. PMID- 28994854 TI - ? AB - Alcoholic ketoacidosis - a review A chronic alcoholic with severe metabolic acidosis presents a difficult diagnostic problem in the emergency room. Over and above methanol- and ethylene glycol intoxication, alcoholic ketoacidosis is a common but less recognized etiology. The disorder occurs in alcoholics who have had a recent binge drinking followed by the abrupt cessation of alcohol consumption because of abdominal pain and vomiting, with resulting dehydration, starvation, and then a beta-hydroxybutyrate dominated ketoacidosis. Laboratory results may be misleading as the common urine-ketone tests may be negative or only weakly positive, since they only respond to acetoacetate. The short-term prognosis is good if treatment including replacement of fluid, electrolytes, glucose and thiamine is provided. However, recent studies have indicated that alcoholic ketoacidosis may be a significant cause of mortality in patients with alcohol dependence. PMID- 28994855 TI - ? AB - Melioidosis, an important diagnosis in the severely ill traveler Melioidosis is a common tropical infection in Southeast Asia and is caused by the highly pathogenic soil bacterium Burkholderia pseudomallei. Diagnosis and treatment is often challenging due to variations in clinical presentation, limited antibiotic susceptibility and high risk of recurring infection. In this report, three cases with different clinical presentations are described. PMID- 28994857 TI - ? PMID- 28994856 TI - ? PMID- 28994859 TI - ? PMID- 28994858 TI - ? PMID- 28994860 TI - ? PMID- 28994862 TI - ? PMID- 28994861 TI - ? PMID- 28994863 TI - ? PMID- 28994864 TI - Tunisian adult's Hodgkin lymphoma Study Group. AB - The Tunisian adult's Hodgkin lymphoma (HL) Study Group was created in 1999. It aimed to improve the management of this curable hematologic malignancy by standardizing the diagnosis, assessment of disease, treatment management and therapeutic evaluation in different Tunisian centers (Hematology, oncology and radiotherapy).Since 1998, four versions of the prospective national protocol for treating adult Hodgkin lymphoma have succeeded (MDH99, MDH2002, MDH2008, MDH2015). Each version was based on the results of the previous version and analyzed according to new data from the literature. Due to this national study group, the number of patients lost to follow decreased significantly (30% before the creation of the group and only 3% for patients treated with MDH2008), the complete and uncertain response rates have improved (75% before the creation of the group and 92% in patients treated with MDH2008) with dramatically improved rates of overall survival from 57% to 90%. On the other hand there was an improvement of toxic death rate (13% of toxic deaths in MDH2002 to 4.37% in the MDH2008) with a decrease of the respective rate of primary failure and relapse by 17% and 12.5% in MDH2002 against the 11.4% and 7.8% in the MDH2008. This resulted in an improvement in overall survival (90%) and event-free survival at 5 years (75%). Now with the introduction of positron emission tomography in Tunisia, we hope yet to finalize the assessment of response and thus better adapt the treatment of this disease. Our objective remains the improvement of event-free survival rate to reach 80%. PMID- 28994865 TI - Value of Cine-MRI sequences before and after injection in the diagnosis of acute myocarditis. AB - BACKGROUND: Cardiovascular magnetic resonance (CMR) has become the examination of choice in case of suspicion of acute myocarditis. Late gadolinium enhancement (LGE) imaging is very important to establish this diagnosis. Cine MRI sequences are useful for the study of the myocardial contractility. AIMS: The purpose is to estimate the value of cine MRI sequences before and after injection for the diagnosis of acute myocarditis compared with late gadolinium enhanced sequences. METHODS: We prospectively included 40 patients having a high suspicion of acute myocarditis and examined using a 1.5 Tesla CMR. Cine MRI sequences before and after injection were performed. The protocol also include T2-weighted short- tau-inversion-recovery (STIR T2) fast spin echo MRI and LGE imaging eight minutes after injection with visual adjustment of inversion time. RESULTS: Delayed enhancement was found among 23 patients. Fifteen patients (65 %) presented a spontaneous hyper signal detected visually on Cine MRI sequences before injection and 11 patients (48 %) on STIR T2. The hyper signal on Cine MRI sequences after injection of gadolinium was the same topography that the late raising at 23 patients. In addition, we highlighted a significant difference between this hyper signal before injection and the left ventricle ejection fraction (p=0.022) as well as with the telesystolic volume of the left ventricle (LV) indexed by the body mass (p=0.039). CONCLUSION: Our study suggests that Cine MRI sequences after injection are of equal performance in the diagnosis of acute myocarditis as the LGE sequences and its contibution is important when we want to shorten the examination or when inversion time isn't optimal. PMID- 28994866 TI - Multiple bile duct stones: Comparison of two surgical techniques done at laparotomy. AB - BACKGROUND: Biliary lithiasis is the most common surgical disease in Tunisia. Multiple bile duct stones are one of his most rare complications.It poses real problems with the best therapeutic approach. AIMS: To analyze the results of conventional surgery for multiple bile duct stones by comparing two techniques: The choledochotomy for stoneextraction followed by external biliary drainage and biliary-enteric anastomosis, to identify and to analyze the factors influencing the therapeuticchoice. METHODS: During study period spanning 16 years, 137 choledochotomy were made for multiple bile duct stones. These patients had either acholedochotomy with stone extraction and then drained through a T-tube or a biliary-enteric anastomosis. RESULTS: Preoperative diagnosis of multiple bile duct stones has been made in 32.1 % of patients. Cholangiography was found in all casesmultiple bile duct stones and had demonstrated an association with intrahepatic stones in 18.2 %. External drainage by a Kehr drain wasperformed in 39.4 % and biliary-enteric anastomosis in 60.6 %. Univariate and multivariate analysis had identified three factors significantlyassociated with external drainage: age <= 65 years, bile duct diameter < 15 mm and the existence of a pronounced inflammatory reaction of thecholedochal wall. No factors had influenced the choice between different bilio-enteric anastomosis techniques. These three techniques did notdiffer from the post operative morbidity (p = 0.84) or mortality (p = 58). CONCLUSION: Basing on the analysis of our series and the comparison with other series reported in the literature, we recommend biliary drainagewith a T-tube in young people under 65 years who have a little dilated bile duct, not exceeding 15mm. In patients aged over 65 years or thosewith a CBD dilated more than 15 mm, even with intrahepatic stones, in cases of distal bile duct stricture or periampullary diverticulum, biliaryentericanastomosis seems to be the safest technique. PMID- 28994867 TI - Mid-terme results of cardiac surgery of valve replacement by mechanical prosthesis. About 861 patients. AB - BACKGROUND: Patients with mechanical valvular prostheses are becoming more numerous in our country. Their medical care poses a number of problems in a particular socio-economic context of our geographical regions. AIM: The purpose of this study was to identify the complications of this heart valve replacement surgery by mechanical prostheses and try to compare our results with those of literature. METHODS: From January 1998 to June 2003, 861 patients were operated for acquired valvular heart disease (413 men and 448 women), average age 39+/-11 years. It was 495 mitral valve replacement, 205 aortic valve replacement, 158 mitral-aortic replacement and 3 aorto-mitral-tricuspid replacement. One hundred seventy eight (178) gestures were needed on the tricuspid valve. RESULTS: Hospital mortality was 6.2% CI [5.0 - 8.5]. Remote 9 years mortality was 21 deaths. No structural deterioration prosthesis occurred. Hospital Morbidity was 14 thromboembolism, 52 hemorrhage and 8 mediastinitis. Remote morbidity was 3 strokes, 2 serious gastrointestinal bleeding and two endocarditis. The survival rate at 5 years was 90 % CI [0.88 - 0.91]. CONCLUSION: Heart valve replacement surgery with mechanical prostheses gives satisfactory results in the medium term. PMID- 28994868 TI - Foodborne outbreak simulation to teach field epidemiology: the Moroccan Field Epidemiology Training Program. AB - BACKGROUND: Morocco in 2010 launched a new field epidemiology training program to enhance the skills of health professionals in charge of epidemiological surveillance and to investigate outbreaks; including foodborne diseases that represent a very substantial burden of disease. AIM: To apply an active learning method to teach outbreak investigation within a controled environment for field epidemiology trainees program at the Moroccan National school of public Health. METHODS: A scenario describing digestive symptoms evoking a restaurant-associated foodborne outbreak that would affect the school staff was designed for the residents to investigate, to assess their organizational capacity and application of all stages of epidemiological investigation. RESULTS: Nine Residents applied study design, database management and statistical analysis to investigate the foodborne outbreak, to estimate attack rates, classify cases and controls, to identify the contaminated foods and pathogens and to issue preventive recommendations for the control and the prevention of further transmission. The overall resident's satisfaction of the learning method was 67%. CONCLUSION: A simulation of an outbreak investigation within an academic setting is an active learning method to be used in the curriculum for introducing the residents on field epidemiology program to the principles and practices of outbreak investigation before their implication in a real situation. PMID- 28994869 TI - Acute acoustic trauma: how to manage and how to prevent? AB - INTRODUCTION: The consequence of an exposure to intense sounds can be a temporary or permanent hearing loss and even with a rapid therapeutic management, severe sensorineural sequelae may persist. METHODS: the authors report a retrospective study about 64 patients followed for an acute acoustic trauma during a period of 8 years (2006 to 2013). For all the cases, a clinical examination associated to a pure-tone audiometry was conducted. Hearing levels were measured at the frequencies 500, 1000, 2000 and 3000 Hertz. Auditory evoked potentials were performed in 17 cases. The therapeutic and evolutive data were detailed and discussed. RESULTS: All our patients were male with a mean age of 34 years. The cause of acoustic trauma was a firing of a gun near the ear in 48 cases, an explosion near the ear in 5 cases and a sudden exposure to loud noises near military planes in 11 cases. Clinical complaints were acute hearing loss with tinnitus. Audiometric exams found a sensorineural hearing loss with a hearing level average of 38 decibels (dB) +/- 14 SD. The therapy consisted of systemic cortisteroids associated in all the cases to peripheral vasodilators. It was given intravenously during 10 days and then orally with vasodilators during one to 3 months. Hyperbaric oxygenotherapy have been administrated for 25 patients. The follow-up consisted of questioning about symptoms, clinical examination and pure-tone audiometry. A good evolution was noted in 52 cases (81%) and the mean of hearing level after therapy was: 24 dB +/- 12 dB. Despite a prolonged therapy with vaso-active drugs, tinnitus persisted in 36 cases. CONCLUSION: Controlling noise and its harmful effects through technical devices and safety professionals programs are the best way to reduce the frequency and the sensorineural sequelae due to acute acoustic trauma. PMID- 28994870 TI - Predictive scores of early mortality from variceal gastrointestinal bleeding in cirrhotic patients. AB - INTRODUCTION: The variceal bleeding, main complication of portal hypertension during cirrhosis, is associated with high early mortality riskestimated between 15 and 20%. This highlights the necessity of predictive models that allow identifying high-risk patients raising the issue of amore aggressive therapeutic care. OBJECTIVE: To assess the performance of four scores for the prediction of cirrhotic patients' high early mortality risk due to digestive hemorrhageand to compare them to the Child-Pugh reference score. METHODS: We collected 87 cirrhotic patients admitted to the Gastroenterology Department of Charles Nicolle Hospital for a high digestivehemorrhage by rupture of gastric or esophageal varicose veins. RESULTS: 56 men and 31 women were included in this study. The average value of Rockall, Glasgow Blatchford, MELD and MELD-Na scores,was respectively equal to 6.19, 10.91, and 17.6 and at 20. Early mortality was 30%. The average value of all the scores was significantly higherwith the prematurely deceased patients (p<0.001). The MELD-Na score had higher sensitivity and specificity for the prediction of prematuremortality compared to the other scores but without statistical significantly difference (Area under the ROC curve: MELD Na=0.867, p<0.001;Child-Pugh=0.809, p<0.001; Rockall=0.777, p=0.001; Glasgow Blatchford=0.761, p<0.001; MELD=0.838, p<0.001). The predictive value of thecut off MELD-Na score was equal to 19 with a sensitivity of 70% and a specificity of 82%. CONCLUSION: The studied four scores had a good predictive value of early mortality risk by varicose digestive hemorrhage with cirrhotic patients. PMID- 28994871 TI - Evaluation of anticoagulation therapy in non-valvular atrial Fibrillation in the emergency department. AB - INTRODUCTION: The vitamin K antagonists (VKAs) are currently the most effective therapeutic class for the prevention of cerebrovascular eventsin atrial fibrillation (AF) patients. However, several studies showed an under-prescription of this therapy.The aim of the study was to assess the prescription of VKAs in non-valvular AF (NVAF) patients and factors influencing the non-prescription ofsuch treatment. METHODS: We conducted a prospective, observational study in an emergency department (ED). Patients with high thromboembolic risk NVAFand not receiving VKAs beforehand were included. Calculation of CHA2DS2-VASc and HAS-BLED scores was performed. An analytic study wasconducted in order to identify independent predictors of the under-prescription of VKAs. RESULTS: During study, 176 patients were enrolled, the mean age was 67+/-13 years and 66% were women. The mean CHA2DS2VASc andHASBLED scores were 2.88 +/- 1.55 and 1.52 +/- 1.05, respectively. Among our cohort, VKA was prescribed in 36% of cases. Age >70 years(OR=1.59, 95%CI[1.11-2.21],p<0.001), creatinine level >=110 MUmol/l (OR=2.54,95%CI[1.20-5.37],p=0.01) and aspirin use (OR =1.7,95%CI [1.08 2.67],p=0.02) were independently associated with under-prescription of VKAs. Bedside, the main causes reported by the emergency physicians(EP) were: factors related to patient characteristics (n=38,34%), factors related to emergency physician (n=62,55%), factors related to the patientenvironment (n=20,17%) and factors related to the drug (n=22,23%). CONCLUSIONS: Our results showed that the prescription of VKAs was low in ED. The reasons of VKA under-prescription are linked usually toseveral factors inherent to patient and to the adherence of EP to new recommendations. PMID- 28994872 TI - Primary Ewing's sarcoma of the sphenoid sinus with orbital and intracranial extension: a case report. AB - Ewing's sarcoma is a high-grade neuroectodermal primary bone tumor. This is the second primary bone tumor in children afterosteosarcoma and represents 4 to10% of cases. It can occur in all skeletal bones. However, the location at the facial bones is uncommon (1to2%) and extremely rare at the sphenoid sinus. We report the clinical results of a rare case of Ewing's sarcoma of the sphenoid with intraorbitaland intracranial extension. PMID- 28994873 TI - Anal imperforation in adults: Diagnostic difficulties and therapeutic options. AB - Anorectal malformations are congenital anomalies ranging from simple perineal fistulas to complex malformations. They are usually treated inchildhood, and exceptionally in adult. We herein report the case of a 22 years aged patient and relate the diagnosis difficulties and therapeuticoptions. She consulted for anal imperforation discovered since birth. Initially, His parents refused the surgical management. It was an analimperforation with a vestibular fistula. The patient was operated by a low approach. She had a disconnection of the recto-vestibular fistula,dissection of the anal canal and a perineal posterior transposition. Postoperative course was uneventful. The evaluation of continence usingKelly's score found good Functional result. PMID- 28994874 TI - Central serous chorioretinopathy after nasal corticosteroids in the aviator. PMID- 28994875 TI - Fetal thrombotic vasculopathy: a rare and serious lesion. PMID- 28994876 TI - Primary adenoid cystic carcinoma, a rare bronchial tumor. PMID- 28994877 TI - Xanthogranuloma of the sellar region. PMID- 28994879 TI - Meckel's diverticulum present as pyogenic liver abscess. PMID- 28994878 TI - Toxic hepatitis and hematologic disorder in a work environment: A case report. PMID- 28994881 TI - Povidone Iodine Pleurodesis for Refractory Congenital Chylothorax: A Review of Literature. AB - BACKGROUND: Povidone iodine (PVI) pleurodesis is commonly used in adult. However, this procedure is still nonconsensual in newborns. AIMS: This article aimed to report a new case of refractory congenital chylothorax (CCT) managed with PVI pleurodesis with a review of previousreported cases. METHODS: a systematic review of similar cases published in PubMed. Clinical patterns, therapeutic modalities and outcome variables werereported. RESULT: In a full term neonate presenting refractory CCT, PVI pleurodesis was performed at day 16 of life by one intrapleural instillation of PVI4% with rapid success and no side effects. Renal function and thyroid tests stilled normal before and after instillation. The analysis of 18 casesreported in Medeline and our observation provided the following data: this procedure was successful without side effects in 11/19 cases. Severeside effects were reported in four patients with high risks before procedure. CONCLUSION: PVI pleurodesis seems to be effective and inoffensive in the management of refractory CCT. It may be a good alternative tosurgery. Nevertheless, randomized studies on large neonatal population are required to precise: the risks and benefits of this procedure, thetiming and the modalities of its realization (duration of intervention, dilution and dosage of PVI) according to the patient's field (gestational age,weight and associated morbidity). PMID- 28994882 TI - Cardiovascular risk estimation in non alcoholic fatty liver disease. AB - BACKGROUND: Nonalcoholic fatty liver disease is rising to the growing epidemic of metabolic syndrome. Recent data suggest that this liver disease may represent a real marker of cardiovascular risk. The aim of our study was to calculate cardiovascular risk and to estimate the frequency of subclinical coronary artery disease by conducting an exercise testing. METHODS: This is a prospective study conducted over a period of one year including all patients followed for non alcoholic fatty liver disease. We realized in all patients an exercise testing and we calculated the ACC / AHA score that estimates the risk of developing atherosclerotic cardiovascular disease. This risk is considered very high if the score> 7.5. RESULTS: We included 103 patients. The mean age was 52 years. The sex ratio (M/F) was 0.3. Diabetes, dyslipidemia and hypertension were present respectively in 45.6%, 48.5% and 38.8% of cases. Obesity was noted in 69.9% of our patients. Metabolic syndrome was found in 78.6% of patients. The ACC / AHA average score was 8.03 +/- 9 and a score> 7.5 was noted in 35.9% of cases. The exercise testing was positive in 12 patients (11.65%). Of these, 11 underwent coronary angiography which was normal in 10 cases and showed a coronary artery infiltration without significant stenosis in only one case, and 2 patients underwent coro-scanner which was without significant anomalies. In univariate analysis, the presence of metabolic syndrome (p = 0.05), waist circumference >= 94 cm in men and >= 80 cm in women (p = 0.019), diabetes (p = 0.03) were associated with a high risk of developing cardiovascular events. In multivariate analysis, the only independent variable associated with a positive exercise testing was diabetes (OR 4.5, p = 0.03). CONCLUSION: During non alcoholic fatty liver disease, there is an increased cardiovascular risk. It would be necessary to consider this excess risk in the surveillance of patients followed for non alcoholic liver disease to early detection of any cardiovascular disease. PMID- 28994883 TI - Long-term outcome of intravesical bacillus Calmette-Guerin therapy with maintenance for urinary bladder carcinoma in situ: About 47 cases. AB - INTRODUCTION: Data concerning the efficacy of intravesical Bacillus Calmette Guerin (BCG) on carcinoma in situ (CIS) of the bladder are limited. OBJECTIVES: We analyzed long-term outcomes of instillation therapy with BCG to treat bladder CIS, evaluated its effectiveness and safety and searched for prognostic factors that could predict disease recurrence and progression. METHODS: Between March 1994 and December 2010, 47 patients (male: 40; female: 7) with median age of 59,5 years (range 40-76 years), diagnosed with bladder CIS underwent weekly BCG instillations (75 mg of Pasteur strain) for six weeks followed by 6 monthly instillations. Patients were collected from four different institututions.Proven bladder CIS diagnosis was made through random biopsy (n=19), macroscopic lesion (n=28) and urinary cytology (n=6).Primary, concomitant, and secondary CIS was found in 13 (27,6%), 28 (59,6%) and 6 (12,7%), patients, respectively. RESULTS: The median follow up period was 67.5 months (range 60-116 months).The recurence rates were 15,4%, 35,7% and 50% respectively in group I,II and III at 5 years follow-up. The overall complete response rate was 68%.The five-year progression free survival rate was 87.2%.Several factors, such as age (<60 or >60 years), gender, previous transurethral resection and type of CIS, were examined by multivariate analysis to predict recurrence and progression. None of them was an independent prognostic factor.Bladder irritation symptoms were the main BCG adverse effects. There were no severe adverse effects requiring discontinuation of drug administration.Radical cystectomy was performed in 5 patients. Extravesical involvement was identified in only one patient. During follow-up period, none died of bladder cancer. CONCLUSION: Therapy with BCG is remarkably effective and safe for primary CIS and concomittent CIS, which might be a prognostic factor. We didn't find any significant risk factor. Recurrence and disease progression including extravesical involvement should be carefully monitored over the long-term after BCG therapy. PMID- 28994884 TI - Trauma of the hand from circular saw table: a series of a 130 cases. AB - INTRODUCTION: Trauma of the hand from a circular saw table is a common occurrence in developing countries it tends to occur in young hand working people and it causes a serious lesions. METHODS: It was a retrospective series about a 130 cases of hand trauma from circular saw table. Epidemiological features, treatment, and permanent disabilities left by hand trauma from circular saw table were studied to identify ways to prevent such an accident. RESULTS: The average age was 31.24 years, these patients were exclusively men, 62% were apprentice wood workers, and the left hand was twice more injured than the right hand. Regarding clinical aspects, in 77% of cases, two or more fingers were injured, tip amputations of the left fingers predominated (49%), in 50% of the cases of hand wounds occurred to the dorsum of the hand, and extensor tendon injuries were observed twice more than flexor tendon injuries. Regarding the surgical treatment, performing an amputation stump was the most practiced primary surgery (107 cases i.e. 82% of primary surgeries). Arthrodesis, reconstructive flap surgery, and spongy bone grafts were the most practiced secondary surgeries (79% of secondary surgeries). Joint stiffness was the most observed complication (26%). CONCLUSION: Hand injuries from circular saw table such as those described in this study will continue to challenge the skill of surgeons devoted to the restoration of function and form to the damaged hand. Prevention, of course, should be the goal because of the severe functional and psychological impairment that may result from them. PMID- 28994885 TI - Management of combat-related facial injuries. AB - INTRODUCTION: Combat-related facial injuries involve various lesions of the mouth, the eye sockets and the facial bones. The goal of this study is to precise the particularities of these affections and their therapeutic management. METHODS: A retrospective study was performed about 56 cases of combat-related facial injuries over a period of 5 years (2010 - 2014). RESULTS: Our study included 56 male patients with an average age of 29 years (20-37). The trauma occurred during a real security intervention in all the cases. It was isolated in 18 cases and associated to other lesions in 38 cases. Clinical examination revealed facial edema (57%), facial cuts and lacerations (74%), broken teeth (14%), nasal deformation (26%), skin defect (16%) and periorbital ecchymosis (32%). The diagnosis retained after clinical examination and imaging exams were: fractures of the mandible (34 cases), of the eye sockets (18 cases), of the nasal bones (15 cases), parotid gland injury (5 cases) and facial arterial injuries in (24 cases). The treatment was surgical in all the cases: stabilization of fractured segments (43 cases), suture of facial and vascular lacerations (51 cases), reduction of nasal fractures (15 cases), and reposition of teeth dislocations (35 cases). The evolution was good in 34 cases. The functional sequelae noted were ophthalmic (7 cases), dental abnormal occlusions (11 cases), residual trismus (4 cases) and facial palsy in 2 cases. CONCLUSION: Combat related facial injuries must be diagnosed and treated early to prevent the functional and, sometimes, life-threatening damages dues to those lesions. PMID- 28994886 TI - Is there a real benefit of hyperbaric oxygenotherapy in the treatment of necrotizing otitis externa? AB - INTRODUCTION: Necrotizing otitis externa remains a severe and sometimes life threatening disease in diabetic patient. Many therapeutic approaches have been described but what about the real benefit of hyperbaric oxygenotherapy in the management of this disease? METHODS: The authors reported a retrospective study about 42 patients treated for necrotizing external otitis over a period of 9 years (2006 to 2014). The patients were treated either by only antibiotherapy (23 cases) or with both antibiotherapy and hyperbaric oxygenotherapy (19 cases). The evolution under treatment was appreciated in the two groups through clinical, biological and radiological parameters. RESULTS: The study included 42 diabetic patients with a mean age of 67 years (50 to 84 years). The sex-ratio M/F was 0.82. The diagnosis of necrotizing otitis externa was assessed through clinical and bacteriologic criteria in diabetic patients. A temporal bone CT-scan and a technetium scintigraphy were performed in order to precise the topography of the disease and the level of bone lysis. Antibiotherapy was prescribed intravenously and then orally for a mean period of 8 weeks (5 to 15 weeks). Hyperbaric oxygenotherapy was given for 19 patients (average: 20 sessions). The recovery was affirmed on clinical, biological and radiological features. Otalgia disappeared at the 11th day of treatment without HOT and at the 5th day with HOT. Otorrhea disappeared at the 6th day of treatment by HOT and at the 13th day without HOT. The recovery or the regression of facial palsy occurred in 75% of the cases when HOT was given. The total recovery from the disease was diagnosed in 36 patients (86%). The rate of recovery was 100% in the group treated by HOT and 74% in the group treated by only antibiotics. The recurrence of the disease was noted in 6 patients that haven't benefited from HOT. The end of the oral therapy was guided by the results of the Gallium bone scintigraphy. CONCLUSION: Hyperbaric oxygenotherapy must be associated in the treatment of necrotizing otitis externa. The results of our study suggest a real benefit of this therapy regarding clinical, biological and radiological parameters of this severe affection. PMID- 28994887 TI - Hepatic hydrothorax: About a hospital serie of 63 cases. AB - BACKGROUND: Hepatic hydrothorax is a less common complication of cirrhosis with an estimated prevalence of 10- 15%. In the vast majority of cases, ascites are also present but significant pleural effusion may develop in patients without ascites. Hepatic hydrothorax is associated with cirrhosis whatever its etiology. The prognosis of hepatic hydrothorax remains unclear and is closely related to available therapeutic options. The aim of our study is to determine the prevalence of hydrothorax in cirrhotic patients, detail its clinical and therapeutic characteristics, and study the evolutive profile of cirrhotic patients with hydrothorax by comparing it to those without hydrothorax. We also search predictive factors of development of this complication in cirrhotic patients. METHODS: We conduct a retrospective and case-control study including 63 cirrhotic patients with hepatic hydrothorax hospitalized in gastroenterology department of Charles Nicolle hospital of Tunis, during a period of fiveteen years, from January 2000 to January 2015. RESULTS: The prevalence of hydrothorax was 14.5%. The mean age was 62 +/- 14 years (range, 22- 86 years). The sex ratio H/F was 1.52. Hepatic hydrothorax was symptomatic in 35 patients. It was right sided in 60%, left-sided in 24% and bilateral in 16% of cases. Hydrothorax was on average size abundance in 54% of cases. It was transsudatif in 52.5% of cases. Hepatitis C was the most frequent cause of cirrhosis (54%). Our results show that hepatic hydrothorax was present with important ascites in 35 patients. Hydrothorax was significantly related to Child-Pugh C severity of cirrhosis (p=0.0001). Hydrothorax occurence was significantly associated with a low level of albumin (p=0.001), an important hyponatremia (p=0.001) and a low prothrombin rate (p=0.02). A therapeutic thoracentesis was performed in 57% of cases. Diuretics based on spironolactone and furosemide were indicated in 30 patients. Evolution was favorable in 19 patients. Refractory hepatic hydrothorax was present in 31 patients. Death, in the days which follow the hospitalisation, was in 13 patients. The 5-years survival rate was 60%. The mean survival time of patients with hepatic hydrothorax was 8.41 years against 10.75 years at patients without hepatic hydrothorax. CONCLUSION: Hepatic hydrothorax is a common complication in our study. The improvement of the prognosis of our patients would require a better therapeutic management and especially the possibility of orthotopic liver transplantation which is the optimal therapeutic option for patients with hepatic hydrothorax. PMID- 28994888 TI - Treatment of inguinal hernia by lichtenstein technique: an open prospective study. AB - BACKGROUND: Treatment of inguinal hernia is still a challenge for the surgeon. The multitude of surgical techniques attests of the difficulty of choosing the best procedure. In the surgical B department of the Charles Nicolle Hospital we have chosen the Lichtenstein technique since 2008. The aim of this study was to evaluate the immediate and long-term results of this technique and to identify the predictive factors of recurrence. METHODS: This open prospective study included all patients who underwent an elective inguinal hernia repair in the surgical B department of the Charles Nicolle Hospital between June 1st 2008 and December 31st 2009. These patients were regularly followed for at least three years. Hernia's recurrence was the primary study endpoint. Postoperative pain, wound complications, urinary complications were secondary endpoints. An univariate and multivariate analysis were performed to identify predictive factor of hernia recurrence. RESULTS: 256 men and eight women were involved in this study with a sex ratio to 32. The average age was 54 years, ranging from 18 to 85 years. we identified seven cases of recurrent hernia (2,6%) with a risk of recurrence at five years equal to 4.9%, 95%CI[4,5 - 5,3].Wound complications were present in 90 patients (34%), dominated by serums seen in 12.1% of cases. The scrotal edema was found in 32 patients (12%). Eight patients kept a postoperative pain after three years of follow-up (3%). The presence of coagulation disorders in pre-operative check-up ( OR 32.25, 95% CI [3.33- 333.3], p = 0.003) and the persistence of pain after one year of intervention ( OR 16.12,95% CI [2.68 -100], p = 0.01) were two predictive factors of hernia recurrence. CONCLUSION: The Lichtenstein technique remains the gold standard technique in the treatment of inguinal hernias by open surgery. It is a safe, simple, reproducible procedure with a low recurrence rate. PMID- 28994889 TI - Heart Rate Beat-to-Beat Slope Change during Six-Minute Walk Test: a Useful Clinical Tool for Estimating Fitness level. AB - BACKGROUND: The six-minute walk test (6MWT) is one of the most common exercise tests and is used to estimate the level of physical fitness. This study aimed to evaluate the feasibility of the beat-to-beat heart rate 6MWT slope (6MWTS) and recovery slope for predicting and estimating the level of physical fitness during 6MWT, instead of depending on the distance covered during the test. METHODS: Seventy healthy adult male subjects aged 18 to 27 years were recruited randomly from the general Saudi population in Riyadh. Using a 50-m corridor, 6MWT was performed according to standardised American Thoracic Society guidelines. RESULTS: The mean distance walked in 6 minutes (470.5+/-64.6 m) and beat-to-beat heart rate (HR) were calculated using a HR monitor. In addition, the body mass index, body surface area, Borg Rating of Perceived Exertion, and maximum predicted HR percentage were also calculated. A stepwise regression equation was used to predict the 6MWT distance (6MWTD), 6MWTS, and recovery slope. There was a significant correlation between 6MWTS and the recovery slope (r= -0.575, p<0.001), between 6MWTS and 6MWTD (r= 0.414, p<0.001), and between recovery slope and 6MWTD (r= -0.454, p<0.001). CONCLUSION: Our findings suggest that both 6MWTS and recovery slope can predict 6MWTD. PMID- 28994890 TI - Errors in preparation and administration of parenteral drugs in neonatology: evaluation and corrective actions. AB - BACKGROUND: The medication iatrogenic risk is quite unevaluated in neonatology Objective: Assessment of errors that occurred during the preparation and administration of injectable medicines in a neonatal unit in order to implement corrective actions to reduce the occurrence of these errors. METHODS: A prospective, observational study was performed in a neonatal unit over a period of one month. The practice of preparing and administering injectable medications were identified through a standardized data collection form. These practices were compared with summaries of the characteristics of each product (RCP) and the bibliography. RESULTS: One hundred preparations were observed of 13 different drugs. 85 errors during preparations and administration steps were detected. These errors were divided into preparation errors in 59% of cases such as changing the dilution protocol (32%), the use of bad solvent (11%) and administration errors in 41% of cases as errors timing of administration (18%) or omission of administration (9%). CONCLUSION: This study showed a high rate of errors during stages of preparation and administration of injectable drugs. In order to optimize the care of newborns and reduce the risk of medication errors, corrective actions have been implemented through the establishment of a quality assurance system which consisted of the development of injectable drugs preparation procedures, the introduction of a labeling system and staff training. PMID- 28994891 TI - Uncommon cause of multinodular thoracic tumors. PMID- 28994892 TI - Bilateral macular hemorrhage and retinitis pigmentosa. PMID- 28994893 TI - Calcified amorphous tumor in right atrium presenting with syncope. PMID- 28994894 TI - Central serous chorioretinopathy after nasal corticosteroids in the aviator. PMID- 28994895 TI - Complete Trisomy 9 with unusual phenotypic associations. PMID- 28994896 TI - Adult granulosa cell tumor of the testis: a case report. PMID- 28994897 TI - Trichoblastoma arising in nevus sebaceus. PMID- 28994898 TI - Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) induced by antituberculous treatment. PMID- 28994899 TI - Prophylactic antibiotics for preventing pneumococcal infection in children with sickle cell disease. AB - BACKGROUND: Persons with sickle cell disease (SCD) are particularly susceptible to infection. Infants and very young children are especially vulnerable. The 'Co operative Study of Sickle Cell Disease' observed an incidence rate for pneumococcal septicaemia of 10 per 100 person years in children under the age of three years. Vaccines, including customary pneumococcal vaccines, may be of limited use in this age group. Therefore, prophylactic penicillin regimens may be advisable for this population. This is an update of a Cochrane Review first published in 2002, and previously updated, most recently in 2014. OBJECTIVES: To assess the effects of antibiotic prophylaxis against pneumococcus in children with SCD in relation to:1. incidence of infection;2. mortality;3. drug-related adverse events (as reported in the included studies) to the individual and the community;4. the impact of discontinuing at various ages on incidence of infection and mortality. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which is comprised of references identified from comprehensive electronic database searches and also two clinical trials registries: ClinicalTrials.gov and the WHO International Registry Platform. Additionally, we carried out handsearching of relevant journals and abstract books of conference proceedings.Date of the most recent search: 19 December 2016. SELECTION CRITERIA: All randomised or quasi randomised controlled trials comparing prophylactic antibiotics to prevent pneumococcal infection in children with SCD with placebo, no treatment or a comparator drug. DATA COLLECTION AND ANALYSIS: Both authors independently extracted data and assessed trial quality. The authors used the GRADE criteria to assess the quality of the evidence. MAIN RESULTS: Five trials were identified by the searches, of which three trials (880 children randomised) met the inclusion criteria. All of the included trials showed a reduced incidence of infection in children with SCD (SS or Sbeta0Thal) receiving prophylactic penicillin. In trials which investigated initiation of penicillin on risk of pneumococcal infection, the odds ratio was 0.37 (95% confidence interval 0.16 to 0.86) (two trials, 457 children) (low-quality evidence), while for withdrawal the odds ratio was 0.49 (95% confidence interval 0.09 to 2.71) (one trial, 400 children) (low-quality evidence). Adverse drug effects were rare and minor. Rates of pneumococcal infection were found to be relatively low in children over the age of five.Overall, the quality of the evidence for all outcomes was judged to be low. The results from the risk of bias assessment undertaken identified two domains in which the risk of bias was considered to be high, these were incomplete outcome data (attrition bias) (two trials) and allocation concealment (selection bias) (one trial). Domains considered to have a low risk of bias for all three trials were selective reporting (reporting bias) and blinding (performance and detection bias). AUTHORS' CONCLUSIONS: The evidence examined suggests that prophylactic penicillin significantly reduces risk of pneumococcal infection in children with homozygous SCD, and is associated with minimal adverse reactions. Further research may help to determine the ideal age to safely withdraw penicillin. PMID- 28994900 TI - Diagnosing and Treating Patients With Mixed Features. AB - Many patients with mood disorders do not experience pure episodes of depression or mania. Rather, these individuals experience mixed presentations. In the past, individuals experiencing mixed mood episodes were often misdiagnosed due to overly strict diagnostic criteria, leading to poor outcomes and treatment response. The addition of the mixed features specifier to the DSM-5 holds promise for improving recognition in patients who may be experiencing mixed symptoms. Furthermore, awareness has grown important warning signs that should be considered risk factors for progression to bipolar disorder and should warrant special clinical attention. Finally, guidelines for patients experiencing depression with mixed features have recently become available to help provide evidence-based treatment to this patient population. . PMID- 28994901 TI - Risk of First Onset Stroke in SSRI-Exposed Adult Subjects: Survival Analysis and Examination of Age and Time Effects. AB - OBJECTIVE: Exposure to selective serotonin reuptake inhibitors (SSRIs) has been shown to increase the risk of stroke. In this study, we investigated age and time effects on the risk of first onset stroke in SSRI-exposed (SSRIEXP) adult subjects. METHODS: We analyzed an 8-year cohort from the National Health Insurance Research Database, Taiwan. Patients were defined as SSRIEXP subjects if they received SSRI prescriptions for at least 2 consecutive months during January 1, 2001, to December 31, 2007. Otherwise, they were categorized as SSRI nonexposed (SSRINONE) subjects. Stroke diagnosis was made according to ICD-9 codes 430-432 (hemorrhagic stroke) and 433-437 (ischemic stroke). RESULTS: Kaplan Meier survival analysis showed a greater probability of first onset stroke in SSRIEXP than SSRINONE subjects (P < .001). The higher incidence rates in SSRIEXP subjects persisted to the 3 year time point. Ischemic/hemorrhagic stroke cumulative incidence ratios were also higher during the first 3 years in SSRIEXP subjects. Analysis of adjusted hazard ratios indicated that younger SSRIEXP subjects were more likely to experience stroke, with a slight increase of risk in subjects older than 65 years. Stratified analysis of ischemic stroke and hemorrhagic stroke resulted in a similar hazard ratio trend. CONCLUSIONS: Use of SSRIs independently increases the risk of stroke across age strata. The risk is higher in younger adult subjects, and the stroke is more likely to be ischemic than hemorrhagic. The underlying mechanisms of stroke may be related to cerebral microbleeding or an overcorrection of hemostasis function. PMID- 28994903 TI - Antidepressant Exposure During Pregnancy and Risk of Autism in the Offspring, 1: Meta-Review of Meta-Analyses. AB - There are no randomized controlled trials of antidepressant drugs to treat depression, or to prevent relapse into depression, during pregnancy; therefore, the safety of antidepressant drug exposure during pregnancy is based on evidence from case-control or cohort studies. Many of these observational studies, during the past decade, examined the risk of autism spectrum disorder (ASD) in exposed offspring. Different studies using different methods and examining different periods of antidepressant exposure before and during pregnancy obtained different results. Studies with adverse outcomes were highlighted in the mass media, whereas those with reassuring outcomes were mostly ignored. Meta-analyses were conducted to reconcile the findings of the different studies and determine the magnitude of the effect size. In the last year or so, at least 6 such meta analyses examined the effects of antidepressant exposure during pregnancy on the risk of ASD in the offspring. The meta-analyses set different study selection criteria and employed different methods of analysis to address different objectives. The findings across meta-analyses have been reasonably consistent. Antidepressant exposure during pregnancy is associated with an increased risk of ASD in the offspring. The risk is decreased after adjusting for confounding variables and is mostly no longer statistically significant after adjusting for maternal mental illness. Additionally, antidepressant exposure is associated with an increased risk of ASD in the offspring even when exposure is limited to the preconception period, when the drugs cannot have a physiological effect on the fetus. These findings suggest that maternal mental illness is an important determinant of the risk of ASD associated with antidepressant exposure during pregnancy. PMID- 28994904 TI - The Yarkand Embassy. PMID- 28994902 TI - Corrected QT Interval and Methadone Dose and Concentrations in Pregnant and Postpartum Women. AB - BACKGROUND: Methadone is a standard treatment for opioid dependence in pregnancy; however, its impact on maternal corrected QT interval (QTc) has not been evaluated. We studied the association between methadone dose and enantiomer specific plasma concentrations and QTc among pregnant and postpartum women and newborns. We assessed the relevance of QTc screening guidelines for pregnant women and infants. METHODS: From 2006 to 2008, plasma methadone concentrations were measured during pregnancy, postpartum, and in cord blood in women treated for opioid dependence at a single treatment program. Electrocardiograms (ECGs) were obtained at peak methadone concentrations in mothers and within 48 hours of birth for infants. Pearson correlations were performed at each time point for QTc and R-methadone, S-methadone, and total methadone concentrations and ratio of R methadone/S-methadone concentrations. RESULTS: Mean (SD) daily methadone dose for the 25 women was 94.2 (39.1) mg during pregnancy and 112.5 (46.6) mg postpartum. During the third trimester, higher methadone dose and R-methadone concentration correlated with longer QTc (Pearson r = 0.67, P < .001 and Pearson r = 0.49, P = .02, respectively), while S-methadone concentration, R-methadone/S-methadone concentration ratio, and total methadone concentration did not. Postpartum, QTc did not significantly correlate with dose or enantiomer concentrations. Infant QTc did not correlate with maternal dose at delivery or enantiomer-specific cord methadone concentrations. In pregnant and postpartum women, 13% and 17%, respectively, had QTc >= 450 ms, as did 19% of infants. CONCLUSIONS: QTc correlated with dose and R-methadone concentration during the third trimester. However, longer QTc was common among women during and after pregnancy. Given the relatively high rate of QTc > 450 ms, an ECG before and after methadone initiation is advisable for pregnant and postpartum women. PMID- 28994905 TI - Professor Liebrich's Operation for Cataract. PMID- 28994906 TI - Case of Cirrhosis of the Left Lung. PMID- 28994907 TI - Carbolic Acid as a Febrifuge. PMID- 28994908 TI - Osteo-Cephaloma of the Humerus. PMID- 28994909 TI - The Water-Supply of Indian Hill Stations. PMID- 28994910 TI - Atisine. PMID- 28994911 TI - A Case of Fish in the Throat. PMID- 28994912 TI - On Sound as a Cause of Pathological Conditions. PMID- 28994913 TI - Extracts from a Report on Leprosy and Yaws in the West Indies. PMID- 28994915 TI - Cinchona Cultivation in the North-Western Provinces and Punjab. PMID- 28994914 TI - Maggots in Nose or So-Called Vermes Nasi. PMID- 28994916 TI - The "Umrit Sagur". PMID- 28994917 TI - Food Equivalents. PMID- 28994918 TI - Surgical Cases in the Mayo Hospital, Lahore. PMID- 28994920 TI - Invaliding. PMID- 28994919 TI - The Etiology of Madura-Foot. PMID- 28994922 TI - Death from Scorpion Sting. PMID- 28994921 TI - Benicassa Cerifera, a Specific for Haemoptysis. PMID- 28994923 TI - The Madras Medical College. PMID- 28994925 TI - What Next? PMID- 28994924 TI - Case of Snake-Bite at Deesa. PMID- 28994926 TI - A Case of Strangulated Hernia Successfully Treated by Inversion. PMID- 28994927 TI - Medical News. PMID- 28994928 TI - Observations on the Liability of Natives of India to Enteric Fever, with Notes of Cases Reported from Abbottabad during the Last Two Years. PMID- 28994929 TI - A Case of Aneurism of the Ascending Aorta. PMID- 28994930 TI - Rupture of the Heart from Concussion. PMID- 28994932 TI - Medical Retiring Fund. PMID- 28994931 TI - Darjeeling as a Sanitarium. PMID- 28994933 TI - On Burdwan Fever. PMID- 28994934 TI - The Grant Medical College, Bombay. PMID- 28994935 TI - Death Caused by Thrusting a Bamboo-Stick into the Rectum. PMID- 28994936 TI - The Hooghly Fever. PMID- 28994937 TI - Quixotic Etiology: Dr. Cuningham on Cholera in Northern India, 1872. PMID- 28994938 TI - Gunshot Wound of Heart Not Immediately Fatal. PMID- 28994939 TI - Contribution to Indian Dietetics No. 2. PMID- 28994940 TI - Curative Value of Indian Hill Climates. PMID- 28994941 TI - Medical News. PMID- 28994942 TI - Cholera in Calcutta during the Year 1873. PMID- 28994944 TI - The Mortality of Thigh Amputations in Bengal. PMID- 28994943 TI - Typhus Fever in Dacca. PMID- 28994945 TI - Report on the Recent Epidemic of Fever in the Rawulpindee Jail. PMID- 28994947 TI - Dr. Cuningham at the Epidemiological Society. PMID- 28994946 TI - Report on the Treatment of Leprosy with Gurjon Oil. PMID- 28994948 TI - Dr. Cuningham at the Epidemiological Society. PMID- 28994949 TI - The Investigation of Indian Fevers. PMID- 28994950 TI - Case of Traumatic Tetanus Treated with Chloral Hydrate: Recovery. PMID- 28994951 TI - Does Cholera Attack Horses? PMID- 28994952 TI - Compound Comminuted Fracture of Right Forearm; Gangrene; Amputation; Tetanus; Death. PMID- 28994953 TI - Congestive Stricture of Urethra; Retention of Urine; Puncture of Bladder. PMID- 28994954 TI - Extracts from a Report on Leprosy and Yaws in the West Indies. PMID- 28994955 TI - Erratum. AB - [This corrects the article on p. 8 in vol. 9.]. PMID- 28994956 TI - Case of Hydrophobia. PMID- 28994957 TI - Elephantiasis of Scrotum and Penis-Amputation. PMID- 28994958 TI - Darjeeling as a Sanitarium. PMID- 28994959 TI - Report on the Recent Epidemic of Fever in the Rawalpindee Jail. PMID- 28994960 TI - Case of Erysipelatous Inflammation of the Face, Neck, and Upper Part of the Chest, Produced by Smoke from "Bhelawah" Wood. PMID- 28994962 TI - Case of Salivary Calculus. PMID- 28994961 TI - On Urethral Lithotrity. PMID- 28994963 TI - Extracts from a Diary Kept during a Visit to Burdwan in September 1873. PMID- 28994964 TI - Medical News. PMID- 28994965 TI - On Burdwan Fever. PMID- 28994967 TI - Eucalyptus Globulus. PMID- 28994966 TI - A Case of Snake-Bite Treated by Injection of Liquor Ammoniae into the Veins: Death. PMID- 28994968 TI - Excision of Carpal Portion of Radius; Cartilaginous, or Bony Union; and Recovery with a Strong Limb. PMID- 28994970 TI - Microscopic Examinations of Air. PMID- 28994969 TI - Cases of Elephantiasis Scroti. PMID- 28994971 TI - Enteric Fever. PMID- 28994972 TI - Retrograde Views on Cholera. PMID- 28994973 TI - Lithotomy Lateral; Calculi Removed Twice, but the Third Time No Calculus Was Found. PMID- 28994974 TI - Report on Treatment of Leprosy with Gurjon Oil. PMID- 28994975 TI - Contributions to Indian Dietetics; No. 1. PMID- 28994976 TI - Medical News. PMID- 28994977 TI - Sir George Campbell. PMID- 28994978 TI - Eucalyptus Globulus: Its Use in Therapeutics and Its Value as a Fever-Destroyer. PMID- 28994979 TI - Chloroform v. Tetanus.-Case of Compound Comminuted Fracturs of Leg; Tetanus; Amputation: Death. PMID- 28994980 TI - Observations on Burdwan Fever. PMID- 28994982 TI - Epidemic Goitre. PMID- 28994981 TI - Report on Cholera in the Jehanabad Subdivision of Burdwan. PMID- 28994984 TI - The Value of European Life in India. PMID- 28994983 TI - A Case of Spina Bifida Cured by Aspiration and Injection of Iodine. PMID- 28994986 TI - Notes of Cases of Aneurism. PMID- 28994985 TI - Notes on Medico-Legal Work in the Punjab. PMID- 28994987 TI - The "Umrit Sagur". PMID- 28994989 TI - The Milk Treatment of Diabetes in the Seventeenth Century. PMID- 28994988 TI - The Localization of Disease. PMID- 28994991 TI - Moribund Medication. PMID- 28994990 TI - Cholera among Assam Tea Coolies in River Steamers. PMID- 28994992 TI - Case of Lipoma, Weighing 29lbs-Excision-Successful Result. PMID- 28994993 TI - Clinical Studies. PMID- 28994994 TI - Burdwan Fever. PMID- 28994995 TI - Cases from Practice. PMID- 28994996 TI - Esmarch's "Bloodless Method" Employed for the Excision of a Scrotal Tumour. PMID- 28994997 TI - Post-Mortem Examination of the Bodies of 6 Individuals Who Died from Poisoning by Arsenic. PMID- 28994999 TI - 1873. PMID- 28994998 TI - Extracts from a Diary Kept during a Visit to Burdwan in September 1873. PMID- 28995000 TI - Medical Retiring Fund. PMID- 28995002 TI - Double Spleen and Kidneys. PMID- 28995001 TI - Congenital Malformation. PMID- 28995003 TI - Report on the Recent Epidemic of Fever in the Rawalpindee Jail. PMID- 28995004 TI - A Case of Perfect Recovery from an Abscess of the Liver Opening into the Lungs. PMID- 28995005 TI - Fibrous Tumour of the Neck and Face: Removal. PMID- 28995006 TI - Nineteen Cases of Cholera Treated by the Hypodermic Injection of Hydrate of Chloral. PMID- 28995007 TI - Old Notes on Malarial Fevers and Cognate Ailments. PMID- 28995008 TI - The Umrit Sagur. PMID- 28995009 TI - Vernacular Medical Education. PMID- 28995010 TI - Case of Elephantiasis of Labia. PMID- 28995011 TI - Cases from Practice. PMID- 28995012 TI - Enteric Fever. PMID- 28995013 TI - Cases from Practice. PMID- 28995014 TI - Medical News. PMID- 28995015 TI - Famine and Fever in Rajpootana. PMID- 28995017 TI - Physiological Researches on the Nature of Cholera. PMID- 28995016 TI - Erratum. AB - [This corrects the article on p. 336 in vol. 8.]. PMID- 28995019 TI - Mortality of Lithotomy in the North-Western Provinces. PMID- 28995018 TI - "Ainhum," or Spontaneous Amputation of the Toes. PMID- 28995020 TI - Scorpion Poisoning. PMID- 28995021 TI - What Are the Duties of a Health Officer. PMID- 28995022 TI - Report on Cholera in the Shahabad District. PMID- 28995023 TI - Medical Retiring Fund. PMID- 28995024 TI - Case of Preputial Calculus. PMID- 28995025 TI - Report on Cholera in the Arrah Jail. PMID- 28995027 TI - Physiological Researches into the Digestive and Absorbing Powers of the Large Intestine. PMID- 28995026 TI - Dr. Livingstone. PMID- 28995029 TI - The Reductio ad Absurdam of Sanitation. PMID- 28995028 TI - Pyaemia in the Horse. PMID- 28995030 TI - Dr. Hutchinson's Glossary of Medical and Medico-Legal Terms. PMID- 28995031 TI - Assistant Surgeons. PMID- 28995032 TI - Cases of Septicaemia Consequent on Operations upon the Scrotum. PMID- 28995033 TI - Two Cases of Tumour of the Upper Jaw. PMID- 28995034 TI - Penal Settlement, Port Blair; Hospital, Ross Island. In Medical Charge of Surgeon Major J. Dougall: Selections from Hospital Practice. PMID- 28995035 TI - Remarks on the Electric Cautery with Cases. PMID- 28995037 TI - Famine Eever in India. PMID- 28995036 TI - On Subcutaneous Injection of Chloral in Asthma. PMID- 28995038 TI - Ulwar Sudder Dispensary. PMID- 28995040 TI - Medical News. PMID- 28995039 TI - Eulogium on Louis, Pronounced at the Annual Meeting of the Academy of Medicine, on the 17th March 1874. PMID- 28995041 TI - Treatment of Cancer of the Cervix Uteri by the Galvanic Cautery. PMID- 28995043 TI - Suicide and Lumbrici. PMID- 28995042 TI - Case of Tubercular Spinal Meningitis with Deposit of Tubercle in the Liver and Peritoneum. PMID- 28995044 TI - Observations on Burdwan Fever. PMID- 28995045 TI - Two Cases of Tetanus after Delivery. PMID- 28995046 TI - Enteric Fever. PMID- 28995048 TI - Titles. PMID- 28995047 TI - Dr Dougall's Treatment of Leprosy with Gurjon-Oil. PMID- 28995050 TI - A Congress on Cholera. PMID- 28995049 TI - An Instance of Water Serving as a Vehicle of Cholera Poison. PMID- 28995051 TI - Correspondence. PMID- 28995053 TI - The Bulrampur Medical School. PMID- 28995052 TI - A Case of Meningocele (Congenital) Complicated with Chronic Hydrocephalus. PMID- 28995055 TI - The Hygiene of Malaria. PMID- 28995054 TI - On Burdwan Fever. PMID- 28995056 TI - The "Umrit Sagur". PMID- 28995057 TI - On Compression of the Artery in Amputation at the Shoulder. PMID- 28995058 TI - Charles Dickens' Consultation with Mr. Syme. PMID- 28995059 TI - Meteorology in India. PMID- 28995060 TI - Medical News. PMID- 28995061 TI - Rhinoplastic Operation. PMID- 28995062 TI - Mortality of Lithotomy in the North-Western Provinces. PMID- 28995063 TI - Irritant Causes of Disease-Cholera. PMID- 28995064 TI - The Calcutta Medical College. PMID- 28995065 TI - The "Umrit Sagur" (6th Paper). PMID- 28995066 TI - Civil Surgeons and Their Duties. PMID- 28995067 TI - The Hydro-Therapeutic Treatment of Intermittent Fevers. PMID- 28995068 TI - Medical News. PMID- 28995069 TI - The Logical Non-Contagiousness of Cholera. PMID- 28995070 TI - Case of Penetrating Wound of the Abdomen with Protrusion of Small Intestine, 3 Feet Long, Treated by Ice, Carbolic Oil, and Opium: Recovery without Peritonitis. PMID- 28995071 TI - Report upon the Epidemic Fever of 1873-74 in the Rawalpindi Jail. PMID- 28995072 TI - Cholera in the Central Provinces in the Year 1873. PMID- 28995073 TI - Medical Administration. PMID- 28995074 TI - Calculus in a Female. PMID- 28995076 TI - Sanitation. PMID- 28995075 TI - Laborious Labour from Impaction of the Head: Craniotomy: Recovery. PMID- 28995077 TI - Death from Inhalation of Poisonous Gases Generated in a Grain Pit or Katee; Post Mortem Examination and Remarks. PMID- 28995078 TI - Snake Poisoning. PMID- 28995079 TI - On Herpes. PMID- 28995080 TI - Lectures on the Vasculo-Cardiacs. PMID- 28995081 TI - Observations on Leprosy and on Its Treatment by Means of Vaporized Carbolic Acid in Union with Watery Vapor. PMID- 28995082 TI - Case of Strychnia Poisoning. PMID- 28995083 TI - Cases of Hospital Gangrene. PMID- 28995085 TI - Cholera and Lumbrici. PMID- 28995084 TI - Gangrene of the Right Leg Consequent on Pott's Fracture; Amputation at Lower Third of Thigh; Tetanus: Recovery. PMID- 28995086 TI - A Case of Gun-Shot Wound of the Forearm Involving Fracture of the Radius. PMID- 28995087 TI - Sloughing Ulcer of Leg: Amputation. PMID- 28995088 TI - Indian Fevers. PMID- 28995090 TI - The Election of Tagore Law Professor. PMID- 28995089 TI - The "Umrit Sagur". PMID- 28995091 TI - Bloodless Operations with Illustrative Cases. PMID- 28995093 TI - Dislocation of the Hip-Reduction by Flexion. PMID- 28995092 TI - Calculus Vesicae in the North-Western Provinces. PMID- 28995095 TI - The Aboo Lawrence School. PMID- 28995094 TI - Prolonged Pyrexia in Children Treated by the Cold Bath; a Few General Remarks upon This System. PMID- 28995097 TI - The Vienna Conference on the Communicability of Cholera. PMID- 28995096 TI - Medical Fees. PMID- 28995098 TI - Elephantiasis of the Female Generative Organs. PMID- 28995099 TI - Report upon the Epidemic Fever of 1873-74 in the Rawalpindi Jail. PMID- 28995101 TI - A Case of Traumatic Gangrene, Following Compound Fracture of Both Bones of the Right Leg, Complicated with a Sloughing Wound of the Thigh; Amputation Upper Third of Femur Seven Days after Accident: Recovery. PMID- 28995100 TI - Notes from Post--Mortem Examinations: Comminuted Fracture of the Skull without Any External Marks of Injury. PMID- 28995103 TI - Enteric Fever in Hazareebagh. PMID- 28995102 TI - On Herpes. PMID- 28995104 TI - Female Medical Education in Madras. PMID- 28995105 TI - Milky Juice of Jatropha Curcas a Powerful Haemostatic. PMID- 28995106 TI - Deputy Surgeon-General H. B. Buckle, C.B. PMID- 28995107 TI - DeRenzy versus Cuningham. PMID- 28995108 TI - A Case of Elephantiasis of the Female External Generative Organs; Excision: Recovery. PMID- 28995110 TI - Civil Surgeons and Charitable Dispensaries. PMID- 28995109 TI - Death from Starvation: Post-Mortem Examination. PMID- 28995112 TI - A Widow and Orphan Fund for the Warrant Medical Officers of the Bombay Presidency. PMID- 28995111 TI - The Nagpore Medical School. PMID- 28995113 TI - Medical Missions. PMID- 28995114 TI - Civil Surgeons and Charitable Dispensaries. PMID- 28995116 TI - Report upon the Epidemic Fever of 1873-74 in the Rawalpindi Jail. PMID- 28995115 TI - Case of Calculus in a Female. PMID- 28995117 TI - The Electric Cautery in the Treatment of Cystic Growths of the Neck. PMID- 28995118 TI - Civil Surgeons and Their Duties. PMID- 28995119 TI - Medical News. PMID- 28995121 TI - The Vizianagram Female Dispensary, Benares. PMID- 28995120 TI - A Case of Traumatic Stricture of Urethra Treated by Perineal Section. PMID- 28995122 TI - Case of Madura Foot. PMID- 28995123 TI - Report on Enteric Fever in 1st Battalion, 11th Regiment, at Subathoo, in 1873. PMID- 28995124 TI - Bismuth in Dysentery. PMID- 28995125 TI - Lectures on the Vasculo-Cardiacs. PMID- 28995126 TI - Cholera and Lumbrici. PMID- 28995127 TI - Cholera and Quarantine. PMID- 28995128 TI - On the Nature and Physiological Action of the Poison of Naja Tripudians and Other Indian Venomous Snakes.-Part I. PMID- 28995130 TI - The Lahore Medical School. PMID- 28995129 TI - An Instructive Case of Nervous Exhaustion Similating Intermittent Fever. PMID- 28995132 TI - A Case of Tetanus Probably Due to Thread Worms and Ottorrhoea; Cure. PMID- 28995131 TI - Double Uterus. PMID- 28995133 TI - The Diagnosis of Fevers. PMID- 28995134 TI - A Health Officer for the Port of Calcutta. PMID- 28995135 TI - Report on an Outbreak of Boils and Ulcers in the 36th Regiment Native Infantry. PMID- 28995137 TI - The Etiology of Madura Foot. PMID- 28995136 TI - Four Cases of Aconite Poisoning. PMID- 28995138 TI - Medical News. PMID- 28995139 TI - Lumbrici and Cholera. PMID- 28995140 TI - Shoulder Pads. PMID- 28995141 TI - A Case of Osteoid Cancer of Forearm: Amputation: Death. PMID- 28995142 TI - Uterine Calculus.-Histogical Examination of a Calculus Obtained by Dr. Amussat in 1829, Proving It to Be a Calcified Myoma. PMID- 28995143 TI - Cholera and Lumbrici. PMID- 28995145 TI - A Case of Rupture of the Spleen, Complicated with Fracture of the Left Temporal Bone and Effusion of Blood on the Right Cerebral Hemisphere. PMID- 28995144 TI - Fever in the Godavery District. PMID- 28995146 TI - Irritant Causes of Disease. PMID- 28995148 TI - Dr. Fayrer. PMID- 28995147 TI - A Case of Strangulated Inguinal Hernia. PMID- 28995149 TI - Remarks on Varix Lymphaticus or Naevoid Elephantiasis. PMID- 28995150 TI - Treatment of Leprosy by Gurjon Oil. PMID- 28995151 TI - Mortality of Lithotomy in the North-Western Provinces. PMID- 28995152 TI - The Milk Treatment in India. PMID- 28995153 TI - Opium as a Prophylactic of Malarious Fevers. PMID- 28995155 TI - Monthly Report of the Medical College Surgical Dispensary for June 1874. PMID- 28995154 TI - Dr. Francis' Vade Mecum. PMID- 28995156 TI - Penetrating Wound of the Head, Protrusion and Loss of Cerebral Substance: Recovery. PMID- 28995158 TI - An Awkward Accident. PMID- 28995157 TI - Remarks Concerning the Nepalese, Chiefly with Reference to the Goorkhas and the Military Classes, Being an Appendix to the Annual Sanitary Report of the 2nd Goorkha Regiment for 1873. PMID- 28995159 TI - The Burdwan Fever. PMID- 28995160 TI - Treatment of Snake-Poisoning by Artificial Respiration. PMID- 28995161 TI - Fever in the Sote Valley, Pergunnah Sumbhul, District Moradabad. PMID- 28995162 TI - A Case of Lacerated and Contused Wound of the Scrotum. PMID- 28995163 TI - Case of Foreign Body in the OEsophagus, Causing Death by Perforation of the Aorta. PMID- 28995164 TI - Reorganization of the Indian Medical Service. PMID- 28995165 TI - A Case of Traumatic Aneurism of the Dorsalis Pedis Artery. PMID- 28995166 TI - Medical News. PMID- 28995167 TI - Cholera in the East. PMID- 28995168 TI - Cholera in Hoshangabad, 1872. PMID- 28995169 TI - Sulphate of Quinine in Remittent Fever. PMID- 28995170 TI - Poisoning by Sub-Cutaneous Insertion of Nux Vomica. PMID- 28995172 TI - Case of Large Enchondromatous Tumour of the Testicle; Removal; Recovery. PMID- 28995173 TI - Chloride of Ammonium in the Treatment of Hepatic Disease in India. PMID- 28995171 TI - Mesmerism (?). PMID- 28995174 TI - Post-Mortem Delivery. PMID- 28995175 TI - Case of Poisoning with Tincture of Aconite. PMID- 28995176 TI - Digitalis as a Cardiac Stimulant. PMID- 28995178 TI - The Study of Meteorology in Bengal. PMID- 28995177 TI - Milk and Cholera. PMID- 28995180 TI - Cholera. PMID- 28995179 TI - The Burdwan Fever. PMID- 28995181 TI - The Contagious Diseases' Act (XIV. of 1868) in the Presidency Towns. PMID- 28995182 TI - Locusts. PMID- 28995183 TI - Cases from Practice. PMID- 28995184 TI - On the Etiology and Hygiene of Cholera. PMID- 28995185 TI - Case of Syphilitic Iritis. PMID- 28995186 TI - Treatment of Carbuncle by Nitrate of Silver. PMID- 28995187 TI - Adulterated Sulphate of Quinine. PMID- 28995189 TI - Cholera. PMID- 28995190 TI - Medical News. PMID- 28995188 TI - Vernacular Medical Education. PMID- 28995191 TI - Cases from Practice. PMID- 28995192 TI - Improvement of Water-Supply. PMID- 28995193 TI - Draining Bengal. PMID- 28995194 TI - The Burdwan Fever. PMID- 28995195 TI - Cholera in St. Peter's College, Agra. PMID- 28995196 TI - On the Pathology and Treatment of Heat Apoplexy. PMID- 28995198 TI - The Burdwan Fever Not to Be "Suppressed by Theory." PMID- 28995197 TI - Notes on Post-Mortem Examinations Conducted in the Pooree District. PMID- 28995199 TI - Chloride of Ammonium in the Treatment of Hepatic Disease in India. PMID- 28995200 TI - A Case of Asiatic Cholera, with Remarks. PMID- 28995201 TI - Typhoid Fever in Dacca. PMID- 28995202 TI - The Indian Medical Service. PMID- 28995204 TI - Medical Club. PMID- 28995203 TI - Cases from Practice. PMID- 28995205 TI - Dengue. PMID- 28995206 TI - Notes from Practice. PMID- 28995207 TI - The Study of Meteorology in Bengal. PMID- 28995208 TI - Treatment of Intermittent Fever by the Hypodermic Injection of Quinine. PMID- 28995210 TI - Malaria. PMID- 28995209 TI - Chylous Urine. PMID- 28995211 TI - Pedantic Language. PMID- 28995213 TI - A Case of Asiatic Cholera, with Remarks. PMID- 28995212 TI - Locusts. PMID- 28995214 TI - Reorganization of the Indian Medical Service. PMID- 28995215 TI - Case of Perforation of Small Intestine. PMID- 28995216 TI - Case Illustrating the Skim-Milk Treatment of Diabetes Mellitus. PMID- 28995217 TI - Adulterated Milk. PMID- 28995218 TI - Treatment of Snake-Poisoning by Artificial Respiration. PMID- 28995219 TI - Cholera in St. Peter's College, Agra. PMID- 28995220 TI - Treatment of Leprosy. PMID- 28995222 TI - Case of Enteric Fever, with Unusual Complications. PMID- 28995221 TI - Irritant Causes of Disease. PMID- 28995223 TI - Adulterated Quinine. PMID- 28995225 TI - Cholera. PMID- 28995224 TI - Medical News. PMID- 28995227 TI - Notes on Post-Mortem Examinations Conducted in the Pooree District. PMID- 28995226 TI - Case of Relapsing Fever in Delhi during the Famine of 1860-61. PMID- 28995229 TI - Cases of Ruptured Spleen. PMID- 28995228 TI - Double-Storied Barracks. PMID- 28995230 TI - Honor to Whom Honor Is Due. PMID- 28995231 TI - Six Cases of Cholera by Muriate of Ammonia. PMID- 28995232 TI - Urethro Vesical Calculus. PMID- 28995233 TI - The Indian Medical Service. PMID- 28995234 TI - An Inquiry into the Circumstances Attending an Outbreak of Cholera in H. M.'s 18th Hussars at Secunderabad in the Month of May, 1871. PMID- 28995235 TI - On Tetanus. PMID- 28995236 TI - Religion, Science and Medicine. PMID- 28995237 TI - A Case of Congenital Malformation. PMID- 28995238 TI - Cases of Snake-Bite. PMID- 28995239 TI - Sanitary Defects in the Calcutta Medical College Hospital. PMID- 28995241 TI - Medical News. PMID- 28995240 TI - Case of Tetanus Treated with Hydrate of Chloral. PMID- 28995243 TI - Medical Meteorology. PMID- 28995242 TI - Cases of Strangulated Hernia. PMID- 28995244 TI - Opium. PMID- 28995246 TI - Treatment of Fever. PMID- 28995245 TI - Enteric Fever in Bengal. PMID- 28995247 TI - Irritant Causes of Disease. PMID- 28995248 TI - Case of Ablation of the Nose, and Partial Union after Replacing the Piece. PMID- 28995249 TI - Cholera on the Oating Tea Estate, Assam. PMID- 28995250 TI - Mortuary Registration in the Central Provinces. PMID- 28995252 TI - The Looshai Expedition. PMID- 28995251 TI - Remarks on the Treatment of "Intermittent" and "Remittent" Fevers by the Hypodermic Injection of Quinine. PMID- 28995253 TI - On Tetanus. PMID- 28995254 TI - Portable Diseases. PMID- 28995255 TI - Cases of Abscess of the Liver Which Occurred among the Men of H. M's 58th Regiment during the Years 1869 and 1870, with Special Reference to the Connection of the Disease with Dysentery. PMID- 28995257 TI - The Calcutta Medical College. PMID- 28995256 TI - Typhoid Fever in Fort William. PMID- 28995258 TI - Lord Mark Ker on "Delhi Boils." PMID- 28995259 TI - Cases from Practice. PMID- 28995260 TI - Post-Mortem Delivery. PMID- 28995261 TI - On Epidemic and Endemic Fever in the Saharunpore District. PMID- 28995262 TI - Promotion in the British Medical Service. PMID- 28995263 TI - Medical News. PMID- 28995264 TI - Physical Degeneracy. PMID- 28995266 TI - Four Cases of Penetrating Wound of the Abdomen with Protrusion of Uninjured Intestines and Omentum-One Case Complicated with Emphysema of the Right Side of the Chest from Wounded Unprotruded Intestines. PMID- 28995265 TI - Remarks on Some of the Symptoms of "Dengue." PMID- 28995267 TI - Cholera. PMID- 28995269 TI - Snake Poisoning. PMID- 28995268 TI - On the Treatment of Intermittent Fevers by Small Doses of Ipecacuanha. PMID- 28995270 TI - Clinical Lectures on Dengue, Delivered at the Medical College. PMID- 28995271 TI - Notes of Hospital Practice. PMID- 28995272 TI - Cases Treated in 1871. PMID- 28995273 TI - Cases from Practice. PMID- 28995274 TI - Spurious Generalization. PMID- 28995275 TI - Cholera. PMID- 28995276 TI - Alcoholism. PMID- 28995277 TI - Cases of Abscess of the Liver Which Occurred among the Men of H. M's 58th Regiment, during the Years 1869 and 1870 with Special Reference to the Connection of the Disease with Dysentery. PMID- 28995278 TI - Nature and Cause of the Changes in Color of the Chameleon. PMID- 28995279 TI - Clinical Lectures on Dengue, Delivered at the Medical College. PMID- 28995280 TI - Hypodermic Injection of Quinine. PMID- 28995281 TI - The Lieutenant-Governor's Minute on Jail Buildings in Bengal. PMID- 28995282 TI - Dispensary Midwifery Practice. PMID- 28995283 TI - Case of Locomotor Ataxy. PMID- 28995284 TI - A Case of Tramnatic Tetanus, Successfully Treated by Hydrate of Chloral. PMID- 28995285 TI - Leprosy. PMID- 28995286 TI - On Wounds of the Throat. PMID- 28995287 TI - Remittent Fever. PMID- 28995288 TI - Cardiac Embolism or Thrombosis in Child-Birth. PMID- 28995289 TI - On Epidemic and Endemic Fever in the Saharunpore District. PMID- 28995291 TI - Notes of London Hospital Practice. PMID- 28995290 TI - Fibrous Tumour of Hand. PMID- 28995292 TI - The Elimination Hypothesis. PMID- 28995293 TI - A Case of Gonorrhoea Treated with Carbolic Acid and Oil. PMID- 28995294 TI - Dengue. PMID- 28995295 TI - Scarlatina in India. PMID- 28995296 TI - Cholera in Calcutta. PMID- 28995297 TI - Cholera among Coolies. PMID- 28995298 TI - Tumour Fatty (Lipoma). PMID- 28995299 TI - Medical News. PMID- 28995300 TI - Two Remarkable Cases of Injury of Head. PMID- 28995301 TI - Discussion on Pyaemia. PMID- 28995302 TI - Typhoid Fever in Fort William. PMID- 28995303 TI - Effect of Alcohol. PMID- 28995304 TI - Cases from Practice. PMID- 28995306 TI - Surgical Cases. PMID- 28995305 TI - Report on the Epidemic of Cholera Prevailing in the Pertabgurh District. PMID- 28995308 TI - Dengue. PMID- 28995307 TI - Memorandum of Hospital Practice. PMID- 28995309 TI - Experiments with Carbolic Acid. PMID- 28995310 TI - Honour to Whom Honour Is Due. PMID- 28995311 TI - Cholera in Calcutta. PMID- 28995313 TI - The Burdwan Fever. PMID- 28995312 TI - A Few Remarks on the Causes of "Insolatio or Heat Apoplexy" with the Line of Treatment Indicated. PMID- 28995314 TI - Milk and Cholera. PMID- 28995316 TI - Mr. Netten Rodcliffe on the "Prospects of Cholera". PMID- 28995315 TI - Case of Poisoning by Gloriosa Superba. PMID- 28995318 TI - Cholera among Assam Coolies. PMID- 28995317 TI - Cases from Practice. PMID- 28995319 TI - Olutkombol in Dysmenorrhoea. PMID- 28995320 TI - Medical News. PMID- 28995321 TI - Enormous Pendulous Tumour Occupying the Whole of the Left Side of the Neck and Parotid Space-Weight 3lb 81/2oz.; Removed Successfully. PMID- 28995322 TI - Cholera. PMID- 28995323 TI - Jungle Fever in Calcutta. PMID- 28995324 TI - Cases of Abscess of the Liver Which Occurred among the Men of H. M.'s 58th Regiment during the Years 1869 and 1870, with Special Reference to the Connection of the Disease with Dysentery. PMID- 28995326 TI - Medical Retiring Fund. PMID- 28995325 TI - Malarious Fevers Attended with Indistinctness of Speech, &c. PMID- 28995328 TI - Royal Medical Benevolent Fund Society of Ireland. PMID- 28995327 TI - Cases from Practice. PMID- 28995329 TI - Cholera. PMID- 28995330 TI - Cases from Practice. PMID- 28995331 TI - An Outbreak of Cholera at Dehing Mookh, in Assam. PMID- 28995332 TI - Lord Napier on Jail Sanitation. PMID- 28995333 TI - Congenital Absence of the Left Kidney. PMID- 28995335 TI - Carbolic Acid; Its Use, External and Internal. PMID- 28995334 TI - Description of a New Bullet Forceps. PMID- 28995336 TI - The Contagious Diseases Act (XIV. of 1868) in the Presidency Towns. PMID- 28995337 TI - Pthisis Simulated by Pneumonia of the Upper Lobes; Diagnosis Discussed. PMID- 28995338 TI - Medical Staff Employed in Burdwan. PMID- 28995339 TI - Three Cases of Tiger Wound. PMID- 28995340 TI - Irritant Causes of Disease. PMID- 28995341 TI - The Times on Indian Cholera. PMID- 28995342 TI - Medical News. PMID- 28995343 TI - Cases of Abdominal Wounds. PMID- 28995344 TI - On Rupture of the Perinaeum. PMID- 28995345 TI - Malarial Ataxy. PMID- 28995347 TI - Dr. Fayrer on Venomous Snakes. PMID- 28995346 TI - Case of Exophthalmos. PMID- 28995348 TI - Adulterated Milk. PMID- 28995349 TI - Enteric Fever. PMID- 28995350 TI - Abstract of Cases of Cholera Treated with Chloral Hydrate. PMID- 28995351 TI - Mr. Campbell on the Working of the Jails of Bengal for 1871. PMID- 28995352 TI - Effect of Opium on Snake-Poison. PMID- 28995354 TI - The Earl of Derby on Sanitation. PMID- 28995353 TI - Filaria Dracunculus or Medinensis at Kherwarrah. PMID- 28995355 TI - Notes on Cholera in the Jounpore District. PMID- 28995356 TI - Two Cases of Tumour. PMID- 28995357 TI - Badly United Fracture of Femur; Refracture. PMID- 28995359 TI - Medical News. PMID- 28995358 TI - On Epidemic and Endemic Fever in the Saharunpore District. PMID- 28995360 TI - A Few Practical Remarks on Midwifery as Practised in India. PMID- 28995362 TI - The Looshai Expedition. PMID- 28995361 TI - On a Case of Depressed Fracture of the Skull. PMID- 28995363 TI - Typhoid Fever in Jounpore Jail. PMID- 28995364 TI - Cholera at Chezzetcook, Halifax, U. S., in 1871. PMID- 28995365 TI - Cholera in Chowringhee. PMID- 28995366 TI - Clinical Lectures on Dengue Delivered at the Medical College. PMID- 28995367 TI - Remarks on the Formation and General Economy of the Native Army in India. PMID- 28995368 TI - A Case of Strangulated Hernia. PMID- 28995369 TI - The Burdwan Fever. PMID- 28995370 TI - Leprosy. PMID- 28995371 TI - Prophylaxis in Periodic Fevers. PMID- 28995372 TI - Amputation of Both Arms; Recovery. PMID- 28995374 TI - The Hot Sulphur Springs at Sonah. PMID- 28995373 TI - Amputation of the Leg. PMID- 28995375 TI - Case of Wolf-Bite. PMID- 28995376 TI - Case of Hydrophobia. PMID- 28995377 TI - Case of Leopord-Bite. PMID- 28995379 TI - Dengue. PMID- 28995378 TI - A Cases of Hydrophobia with Endocarditis as a Marked Symptom. PMID- 28995381 TI - Cholera. PMID- 28995380 TI - Cases of Abscess of the Liver Which Occurred among the Men of H. M's 58th Regiment during the Years 1869 and 1870 with Special Reference to the Connection of the Disease with Dysentery. PMID- 28995382 TI - The Lancet Versus Intestinal Lesions in Cholera. PMID- 28995383 TI - Medical News. PMID- 28995385 TI - Goitre. PMID- 28995384 TI - Notes with the Lushai Field Force, Left Column. PMID- 28995387 TI - An Inquiry into the Endemic Skin Diseases of India. PMID- 28995386 TI - Reminiscences of an Attack of Dengue. PMID- 28995388 TI - Syme's Operation at the Ankle Joint for Cartilaginous Tumour of the Left Foot, Involving the Tarsal and Metatarsal Bones; Result, Cure. PMID- 28995390 TI - Cholera in Chowringhee. PMID- 28995389 TI - Short Practical Remarks on the Nature, Diagnosis, Treatment, Prevention of Delhi Ulcers. PMID- 28995391 TI - External Application of Carbolic Acid in Cases of Small-Pox. PMID- 28995392 TI - Deaths from Coal Gas. PMID- 28995393 TI - Cases of "Rotheln" Followed by Renal Dropsy. PMID- 28995394 TI - Clinical Lectures on Dengue Delivered at the Medical College. PMID- 28995395 TI - A Case of Foreign Body in the Cornea; Removal and Rapid Recovery. PMID- 28995396 TI - Water-Supply to European Troops in India. PMID- 28995398 TI - On Epidemic and Endemic Fever in the Saharunpore District. PMID- 28995397 TI - Cases from Practice. PMID- 28995399 TI - Medical Man and Court Honours. PMID- 28995400 TI - Irritant Causes of Disease. PMID- 28995402 TI - Medical Meteorology. PMID- 28995401 TI - Cholera in Calcutta. PMID- 28995403 TI - Simple Auriscope. PMID- 28995405 TI - Royal Medical Fund Society of Ireland. PMID- 28995404 TI - Report on the Outbreak of Cholera at Delhi. PMID- 28995406 TI - The Medical College Hospital. PMID- 28995407 TI - An Indian Asylum. PMID- 28995408 TI - Case of Tumour of the Scalp. PMID- 28995409 TI - Cases of Enteric Fever. PMID- 28995410 TI - Irritant Causes of Disease. PMID- 28995411 TI - Lord Mark Kerr on the Delhi Sore. PMID- 28995412 TI - How Scarlatina Is Imported into India. PMID- 28995414 TI - Purulent Infection. PMID- 28995413 TI - Cholera. PMID- 28995415 TI - Darwinism. PMID- 28995416 TI - A Case of Spontaneous Version Terminated within 13 Hours. PMID- 28995417 TI - Medico-Legal Cases. PMID- 28995418 TI - Notes on the Eruptive Fever Prevailing in and around Calcutta. PMID- 28995419 TI - Dengue. PMID- 28995420 TI - On Malarial Fevers and Sites, Relating Chiefly to Assam. PMID- 28995421 TI - Clinical Lecture on Dengue Delivered at the Medical College. PMID- 28995422 TI - An Explanation by the Editors of the Indian Medical Gazette. PMID- 28995423 TI - Remarks on a Case of "Morbillose Blutdissolution," or the So-Called Morbillous Dissolution of the Blood. PMID- 28995424 TI - Typhoid Fever in Jounpore Jail. PMID- 28995426 TI - Fever in Burdwan. PMID- 28995425 TI - Cases of Traumatic Tetanus (Amputation). PMID- 28995428 TI - Skin Grafting. PMID- 28995427 TI - Notes of Three Typical Cases of the Eruptive Fever Which Has Lately Prevailed in Calcutta. PMID- 28995429 TI - Religion, Science, and Medicine. PMID- 28995431 TI - Medical News. PMID- 28995430 TI - Three Cases of Amputation of the Upper Extremity. PMID- 28995432 TI - Ligature of the Subclavian for Axillary Aneurism. PMID- 28995433 TI - Post-Mortem Delivery. PMID- 28995435 TI - Medical News. PMID- 28995434 TI - Case of Scrotal Fistula Discharging Calculous Matter. PMID- 28995436 TI - Cases of Small-Pox Treated by the External Application of Carbolic Acid. PMID- 28995438 TI - The Aboo Lawrence School. PMID- 28995437 TI - Report on an Outbreak of Cholera in the Rajmehal Jail. PMID- 28995439 TI - Adulterated Sulphate of Quinine. PMID- 28995440 TI - On the Etiology and Hygiene of Cholera. PMID- 28995441 TI - Amputation of Thigh; Recovery. Two Cases of Enteric Fever; Recovery. PMID- 28995442 TI - Irritant Causes of Disease. PMID- 28995443 TI - Experiments with Carbolic Acid. PMID- 28995444 TI - Transported by Order of "Medicine". PMID- 28995445 TI - Prevention Is Better Than Cure. PMID- 28995446 TI - Cases of Lightning Stroke. PMID- 28995447 TI - Cases of Abscess of Liver Which Occurred among the Men of H.M.'s 58th Regiment during the Years 1869 and 1870, with Special Reference to the Connection of the Disease with Dysentery. PMID- 28995448 TI - Notes on Post-Mortem Examinations Conducted in the Pooree District. PMID- 28995450 TI - The Burdwan Fever. PMID- 28995449 TI - East Indian Finance Committee. PMID- 28995451 TI - Dr. Burdon Sanderson on Pyaemia. PMID- 28995452 TI - Correspondence. PMID- 28995453 TI - Case of Calculus Vesicae. PMID- 28995454 TI - Case of Atresia Oris. PMID- 28995455 TI - A Case of Suicidal Poisoning by Arsenic, Illustrative of the Extreme Insolubility of the Poison; Two Lumps of Arsenic, Weighing 105 Grains, Passed per Rectum; Recovery. PMID- 28995456 TI - Professor Pettenkofer on Pilgrims and Puri. PMID- 28995457 TI - Reversion. PMID- 28995459 TI - Poisoning by Chloroform. PMID- 28995458 TI - Chloride of Ammonium in the Treatment of Hepatic Disease in India. PMID- 28995461 TI - Cholera. PMID- 28995460 TI - A Case of Asiatic Cholera, with Remarks. PMID- 28995462 TI - Cases from Practice. PMID- 28995464 TI - Case of Extirpation of Eyeball for Disease Affecting Sympathetically the Sound Eye. PMID- 28995463 TI - Cholera in Calcutta. PMID- 28995465 TI - Case of Snake-Bite Treated by Means of Liquor Ammoniae, Administered Subcutaneously and Internally. PMID- 28995466 TI - Report upon the Epidemic Fever of 1873-74 in the Rawalpindi Jail. PMID- 28995467 TI - Observations on Leprosy and on Its Treatment by Means of Vaporized Carbolic Acid in Union with Watery Vapor. PMID- 28995468 TI - Liquor Lyttae in Scorpion Sting. PMID- 28995469 TI - Cholera in Russia. PMID- 28995470 TI - Correspondence. PMID- 28995472 TI - Case III.-Scrotal Elephantiasis and Haematocele: Tapping: Inflammation and Sloughing of Scrotum: Removal of Elephantoid Mass: Tetanus: Death. Under the Care of Dr. K. McLeod. PMID- 28995471 TI - Witchcraft in Rajpootana. PMID- 28995473 TI - Medical News. PMID- 28995474 TI - Civil Surgeons and Charitable Dispensaries. PMID- 28995475 TI - Lectures on the Vasculo-Cardiacs. PMID- 28995476 TI - On Herpes. PMID- 28995477 TI - Cases of Madura Foot Disease. PMID- 28995478 TI - Case II.-Compound Comminuted Fracture of Leg: Tetanus: Amputation: Death. Under the Care of Dr. K. McLeod. PMID- 28995480 TI - Observations upon Some Severe Injuries of the Skull and Brain. PMID- 28995479 TI - On the Nature and Physiological Action of the Poison of Naja Tripudians and Other Indian Venomous Snakes: Part I. PMID- 28995481 TI - Small-Pox in the Central Provinces in the Year 1873. PMID- 28995482 TI - Case I.-Compound Dislocation of Ankle Joint and Compound Fracture of Tarsus: Excision: Recovery. Under the Care of Dr. K. McLeod. PMID- 28995483 TI - Plaster Bandage in Gunshot Fractures. PMID- 28995485 TI - A Sanitarium for Calcutta. PMID- 28995484 TI - Case of Idiopathic Tetanus Treated by Means of Hydrate of Chloral, Which Apparently Gave Rise to Ecchymosed Patches on the Face and Other Parts of the Body, as Well as Aphthous Inflammation of the Mouth. PMID- 28995486 TI - A Week's Practice in the Saharunpore Dispensary. PMID- 28995488 TI - Subcutaneous Injection of Quinine: From the Annual Report of the Regiment. PMID- 28995487 TI - Notes on the Diffusion of Cholera. PMID- 28995489 TI - Severe Wound of the Head by a Bear. PMID- 28995491 TI - Scarlatina in the Hills (Query, "Rotheln."). PMID- 28995490 TI - The Subcutaneous Injection of Quinine. PMID- 28995493 TI - Our Sub-Assistant Surgeons. PMID- 28995492 TI - Hypodermic Injection of Quinine. PMID- 28995494 TI - Practising and Non-Practising Medical Officers. PMID- 28995495 TI - Abstract by the House Surgeon, of Cases of Strangulated Hernia. PMID- 28995497 TI - Crowners' Quests. PMID- 28995496 TI - Royal Irish Benevolent Fund Society. PMID- 28995498 TI - The Site of Impregnation and Extra Uterine Pregnancy Explained. PMID- 28995499 TI - Case of Rupture of the Spleen. PMID- 28995500 TI - Selections from Ophthalmic Practice in the Cowasjee Jehangheer Hospital, Bombay. PMID- 28995501 TI - Medical News. PMID- 28995502 TI - Correspondence. PMID- 28995503 TI - Sun-Stroke. PMID- 28995504 TI - Indian Cholera. PMID- 28995505 TI - Case of Injury to the Small Intestines, Causing Death. PMID- 28995506 TI - Hydrate of Chloral in Tetanus. PMID- 28995507 TI - Ophthalmic Surgery. PMID- 28995508 TI - The Murree Sanitarium. PMID- 28995509 TI - The Cause of Hill Diarrhoea Exemplified by the Sickness from the Disease in the Dhurmsalla. PMID- 28995510 TI - Puchmurree: Proposed New Station for British Troops. PMID- 28995511 TI - Report on Sanitary Improvements in India. PMID- 28995512 TI - Rain-Fall of Simla for 1870. PMID- 28995513 TI - Medical News. PMID- 28995514 TI - Diseased Meat. PMID- 28995515 TI - Hydatid Cysts (Echinococcus Hominis) and Tropical Abscess. PMID- 28995516 TI - Injection of Serum in Cholera. PMID- 28995517 TI - Report on the Action of Quinodine and Cinchonine, as Regards Their Influence on Malarious Fevers. PMID- 28995518 TI - Hospital 1/5th Fusiliers: Case of Softening of the Brain. PMID- 28995521 TI - New Sanitaria. PMID- 28995522 TI - Vaccination in Bengal. PMID- 28995519 TI - Azimgunge Dispensary. PMID- 28995520 TI - Cinchona Alkaloids. PMID- 28995523 TI - On the Curability of Leprosy. PMID- 28995524 TI - Delhi Boils. PMID- 28995526 TI - Presidency General Hospital: Case of Abscess Treated Antiseptically, with Carbolic Acid. PMID- 28995525 TI - Selections from Ophthalmic Practice in the Cowasjee Jehangheer Hospital, Bombay. PMID- 28995527 TI - Regulation of Lodging-House at Pooree. PMID- 28995528 TI - Fever in the Saharunpore District. PMID- 28995529 TI - Ague and Its Sequelae. PMID- 28995530 TI - Injury to the Cervical Vertebrae. PMID- 28995532 TI - Native Students. PMID- 28995531 TI - List of Cases Treated by the Subcutaneous Injection of Quinine in the Hoshungabad Police Hospital during 1869. PMID- 28995533 TI - On the Curability of Leprosy. PMID- 28995534 TI - Contribution to the Vital Statistics of the Punjab. PMID- 28995535 TI - Calabar Bean in Tetanus. PMID- 28995536 TI - Correspondence. PMID- 28995537 TI - Selections from Ophthalmic Practice in the Cowasjee Jehangheer Ophthalmic Hospital, Bombay. PMID- 28995539 TI - A Case of Protracted Labour, Extending over 102 Hours. PMID- 28995538 TI - Mortuary Registration in India. PMID- 28995540 TI - A Description of "Aboojee Pahar" or Mount Aboo. PMID- 28995541 TI - Fracture of the Base of the Skull; Recovery. PMID- 28995542 TI - Cases Illustrative of Two Common Causes of Death after Amputation. PMID- 28995544 TI - Scarlatina Unknown in India. PMID- 28995543 TI - The Medical and Sanitary Services. PMID- 28995545 TI - Our Netley Men. PMID- 28995546 TI - Quinine in Ague. PMID- 28995547 TI - Medical News. PMID- 28995549 TI - Marriageable Age of Natives. PMID- 28995548 TI - A Case of Strangulated Direct Inguinal Hernia. PMID- 28995550 TI - Vaccination and Syphilis. PMID- 28995551 TI - Caution to Bathers. PMID- 28995552 TI - Hypodermic Injection of Quinine. PMID- 28995553 TI - Ipecacuanha in Dysentery. PMID- 28995554 TI - Case of Penetrating Wound of the Bladder; Recovery. PMID- 28995556 TI - Cholera in the Bengal Presidency during 1871. PMID- 28995555 TI - Field Surgery on the North-West Frontier. PMID- 28995557 TI - Case of Cobra Bite. PMID- 28995559 TI - A Description of "Aboojee Pahar" or Mount Aboo. PMID- 28995558 TI - Ipecacuanha in Dysentery. PMID- 28995560 TI - On the Influence of Liquor Ammoniae Hypodermically Injected. PMID- 28995561 TI - Alcoholism. PMID- 28995562 TI - Wound of Abdomen, with Protrusion of Bowel; Recovery with Artificial Anus. PMID- 28995563 TI - Contribution to the Vital Statistics of the Panjab. PMID- 28995564 TI - Case of Rupture of the Uterus. PMID- 28995565 TI - A Case of Filaria in a Horse's Eye. PMID- 28995566 TI - Case of Penetrating Wound of the Abdomen, with Protrusion of Omentum; Recovery. PMID- 28995568 TI - The Indian Medical Service. PMID- 28995567 TI - List of Cases Treated by the Subcutaneous Injection of Quinine in the Hoshungabad Police Hospital during 1869. PMID- 28995570 TI - Notes from Practice:-Stricture. PMID- 28995569 TI - Cases Treated during the Month of April. PMID- 28995571 TI - Experiments on Snake Poison. PMID- 28995572 TI - The Thanatophidia of India. PMID- 28995573 TI - Spontaneous Combustion. PMID- 28995574 TI - On Fish as Food, or the Reputed Origin of Disease. PMID- 28995575 TI - Case of Aortic Aneurism. PMID- 28995576 TI - Abstract of Eight Cases of Amputation at the Hip-Joint. PMID- 28995577 TI - The Peshawar Fever. PMID- 28995578 TI - Case of Elephantiasis Scroti. PMID- 28995579 TI - Suggestions on the Prevention of Heat Apoplexy among European Troops in India. PMID- 28995580 TI - On the Curability of Leprosy. PMID- 28995581 TI - Traumatic Mydriasis. PMID- 28995582 TI - Extracts. PMID- 28995583 TI - The Drainage and Conservancy of Calcutta. PMID- 28995584 TI - On the Immediate Treatment of Persons Bitten by Venomous Snakes. PMID- 28995585 TI - Report of Ophthalmic Practice in the Cowasjee Jehanghier Hospital, Bombay, during the Month of August 1870. PMID- 28995586 TI - Chandney Hospital, Calcutta. PMID- 28995587 TI - On the Sanitary Services of Armies in War. PMID- 28995588 TI - On Fish as Food, or the Reputed Origin of Disease. PMID- 28995589 TI - Dr. Fayrer's Observations and Experiments on Venomous Snakes. PMID- 28995590 TI - A Mirror of Hospital Practice. PMID- 28995591 TI - The Thanatophidia of India. PMID- 28995592 TI - Moorshedabad City Dispensary. Case of Lithotomy. PMID- 28995593 TI - The Peshawar Fever. PMID- 28995595 TI - Summary of Experiments on the Influence of Snake Poison. PMID- 28995594 TI - The Murree Sanitarium. PMID- 28995597 TI - The Proposed Bill to Facilitate Drainage and Irrigation in Bengal. PMID- 28995596 TI - Bustee Dispensary Cases. PMID- 28995598 TI - Hospital of 1/25th Royal Artillery. A Curious Case. PMID- 28995600 TI - On Malarial Sites and Fevers, Relating Chiefly to Assam. PMID- 28995599 TI - Case of Rupture of the Womb. PMID- 28995601 TI - Scarlatina in India. PMID- 28995602 TI - Case of Poisoning by Dhatoorah. PMID- 28995603 TI - Report on the Kohat Water-Supply. PMID- 28995604 TI - Scarlatina Known in India. PMID- 28995605 TI - Case of Rupture of the Stomach, Produced by Violence, the Body Having Been Hung up after Death to Simulate Suicidal Hanging. PMID- 28995606 TI - A Month's Experience in the Surgical Wards of Hutteesing's Hospital, Ahmedabad. PMID- 28995607 TI - Selections from Ophthalmic Practice in the Cowasjee Jehangheer Ophthalmic Hospital, Bombay. PMID- 28995608 TI - Furlough Rules and Civil Surgeons. PMID- 28995609 TI - Cases of Ague-3 Quotidian, 4 Tertian-Treated by Hypodermic Injection. PMID- 28995610 TI - Dr. Parkes' Croonian Lectures. PMID- 28995611 TI - Treatment of Bubo. PMID- 28995613 TI - Natural Science. PMID- 28995612 TI - Correspondence. PMID- 28995614 TI - Intramural Fibroid Tumour, Probably of 11 Years' Standing; Removal by Laceration and Enucleation; Recovery. PMID- 28995615 TI - Scarlatina in Poona. PMID- 28995616 TI - Field Surgery on the North-West Frontier. PMID- 28995617 TI - Medical News. PMID- 28995619 TI - The Narculdangah Slaughter-House. PMID- 28995618 TI - Case of Sunstroke Treated by Depletion. PMID- 28995620 TI - A Series of Cases of Disease of the Nostrils. PMID- 28995621 TI - Another Antidote for Snake Poison. PMID- 28995622 TI - Case of Strangulated Direct Inguinal Hernia. PMID- 28995623 TI - Treatment of Bubo. PMID- 28995624 TI - Notes on a Case of Leucoderma. PMID- 28995626 TI - The Subordinate Medical Service. PMID- 28995625 TI - The Main Drainage Works of London. PMID- 28995628 TI - The Health of the Children of Our European Soldiers in India. PMID- 28995627 TI - Intussusceptions-Complicated Case. PMID- 28995630 TI - Fatal Case of Snake Bite. PMID- 28995629 TI - Case of Aneurism of the Femoral Artery; Deligation at the Apex of Scarpa's Triangle; Recovery. PMID- 28995631 TI - The Treatment of Snake-Bite. PMID- 28995632 TI - The Results of the Cinchona Commission. PMID- 28995633 TI - Selections from Ophthalmic Practice in the Cowasjee Jehangheer Ophthalmic Hospital, Bombay. PMID- 28995634 TI - Case of Epilepsy Treated by Chloral Hydrate. PMID- 28995635 TI - Case of Abscess of the Liver: Of Hydatid Origin. PMID- 28995636 TI - Medical News. PMID- 28995637 TI - Asiatic Cholera in Russia. PMID- 28995638 TI - Scarlatina at Sealkote. PMID- 28995639 TI - The Treatment of Dysentery. PMID- 28995640 TI - On Malarial Sites and Fevers Relating Chiefly to Assam. PMID- 28995641 TI - Thoughts on the Origin of Disease. PMID- 28995642 TI - Simple Epileptiform Neuralgia (Trousseau). PMID- 28995643 TI - The Superintendence of Jails, Bengal. PMID- 28995644 TI - The Income Tax Minute. PMID- 28995645 TI - The Table of Precedence. PMID- 28995646 TI - A Plan for the Extension of Vaccination. PMID- 28995647 TI - Ipecacuanha in Dysentery. PMID- 28995648 TI - A Case of Monstrosity. PMID- 28995649 TI - Medical News. PMID- 28995650 TI - Cultivation of Ipecacuanha in India. PMID- 28995651 TI - Scarlatina in Calcutta. PMID- 28995652 TI - Enteric Fever in Bengal. PMID- 28995653 TI - Case of Perforation of Stomach from Chronic Ulceration. PMID- 28995654 TI - A Case of Scarlatina Maligna. PMID- 28995655 TI - The Physiological and Therapeutical Effects of Carbolic Acid Administered Internally. PMID- 28995656 TI - Scarlatina in India. PMID- 28995657 TI - The Howrah General Hospital. PMID- 28995658 TI - Hyposulphite of Soda in Ague. PMID- 28995660 TI - Blaney to the Rescue. PMID- 28995659 TI - Cases of Datura Poisoning, with Remarks on the Antidote. PMID- 28995661 TI - Selections from Ophthalmic Practice in the Cowasjee Jehangheer Ophthalmic Hospital, Bombay. PMID- 28995663 TI - Royal Medical Benevolent Fund Society of Ireland. PMID- 28995662 TI - On Malarial Sites and Fevers Relating Chiefly to Assam. PMID- 28995665 TI - Mofussil Dispensary Practice. PMID- 28995664 TI - Case of Rupture of the Urethra; Extravasation of Urine; Extensive Sloughing; Recovery. PMID- 28995667 TI - Cholera Maps. PMID- 28995666 TI - Poisoning by Opium-Death. PMID- 28995668 TI - The Antiseptic Method of Treatment in Surgery. PMID- 28995669 TI - Sanitary Progress. PMID- 28995670 TI - Cases from Practice. PMID- 28995671 TI - Relapsing Fever in Lower Bengal. PMID- 28995672 TI - A Case of Recovery after Swallowing Strong Sulphuric Acid. PMID- 28995673 TI - List of Cases Treated by the Subcutaneous Injection of Quinine in the Hoshungabad Police Hospital during 1869. PMID- 28995674 TI - How Does Ipecacuanha Cure Dysentery? PMID- 28995675 TI - Hill Diarrhoea. PMID- 28995676 TI - Cases from Practice. PMID- 28995678 TI - The Indian Medical and Sanitary Departments. PMID- 28995677 TI - A Case of Self-Strangulation. PMID- 28995679 TI - Medical News. PMID- 28995680 TI - Bustee Dispensary-Cases from Practice. PMID- 28995681 TI - Poisoning by "Kurwa Thumree"-Cucarbita Sagenaria. PMID- 28995683 TI - Epidemic Intermittent Fever in the Mauritius. PMID- 28995682 TI - Ague and Its Sequelae. PMID- 28995684 TI - Reparative Operation for Cicatrix with Skin Grafting. PMID- 28995686 TI - Dr. Royston Piggott's Addition to the Microscope. PMID- 28995685 TI - Selections from Ophthalmic Practice in the Cowasjee Jehangheer Ophthalmic Hospital, Bombay. PMID- 28995687 TI - The Contagious Diseases' Act. PMID- 28995688 TI - Observations on the Power That Round Worms (Nematelmia) Possess to Penetrate the Tissues of the Body. PMID- 28995689 TI - A Few Remarks on Sun-Stroke. PMID- 28995690 TI - A Very Large Ulcer on the Leg; Transplantation of Skin; Rapid Cure. PMID- 28995691 TI - Dr. Bennett and Army Surgeons. PMID- 28995693 TI - Case of Spontaneous Rupture of the Spleen. PMID- 28995692 TI - A Curious Form of Eruptive Fever in Calcutta. PMID- 28995694 TI - On Malarial Sites and Fevers, Relating Chiefly to Assam. PMID- 28995695 TI - Case of Gun-Shot Wound of the Hand. PMID- 28995696 TI - Notes of London Hospital Practice. PMID- 28995698 TI - The Physiological and Therapeutical Effects of Carbolic Acid Administered Internally. PMID- 28995697 TI - A Clinical Lecture on Colles's Fracture. PMID- 28995700 TI - Dengue-Scarlatina Rheumatica. PMID- 28995699 TI - Correspondence. PMID- 28995702 TI - The Secunderabad Cholera of 1871. PMID- 28995701 TI - Report on the Prevailing Diseases in the Madhopore District. PMID- 28995703 TI - Diabetes in India. PMID- 28995705 TI - Rumoured Changes in the Indian Medical Service. PMID- 28995706 TI - Medical News. PMID- 28995704 TI - Two Cases of Snake-Bites. PMID- 28995707 TI - Scarlatina in India. PMID- 28995709 TI - The Subordinate Medical Department. PMID- 28995708 TI - An Inquiry into the Circumstances Attending an Outbreak of Cholera in H. M.'s 18th Hussars at Secunderabad in the Month of May, 1871. PMID- 28995710 TI - Malarious Poisoning; Carbuncular Condition of the Cheek; Death from Pulmonary Embolism. PMID- 28995712 TI - Indian Medical Service. PMID- 28995711 TI - A Case of Malarious (?) Albuminuria Successfully Treated. PMID- 28995713 TI - Impregnation without Rupture of Hymen. PMID- 28995714 TI - Poisonous Effects of Goonj (Seeds of Abrus Pecatorius.). PMID- 28995715 TI - Enteric Fever in Bengal. PMID- 28995716 TI - Penetrating Wound of Abdominal Cavity with Protrusion; Recovery. PMID- 28995717 TI - Mofussil Dispensary Practice. PMID- 28995718 TI - Remarks on the Value of Quinine as a Prophylactic. PMID- 28995719 TI - Gondah Dispensary Cases. PMID- 28995720 TI - How the Bite of Snakes-Supposed to Be Poisonous-May Be Cured. PMID- 28995721 TI - Medico-Legal Notes. PMID- 28995723 TI - Relapsing Fever in Lower Bengal. PMID- 28995722 TI - Case of Gun-Shot Wound. PMID- 28995724 TI - Epithelioma Involving Both the Upper and Lower Lips and the Insides of the Cheeks; Formation of a New Lower, and Re-Modelling of the Upper Lip, &c. PMID- 28995725 TI - The Late Surgeon James Fawcus. PMID- 28995726 TI - Case of Extreme Cardiac Hypertrophy and Dilatation. PMID- 28995727 TI - Rumoured Changes in the Bengal Medical Service. PMID- 28995728 TI - Cholera at Secunderabad. PMID- 28995729 TI - District Sanitation. PMID- 28995730 TI - The Antiseptic Method of Treatment in Surgery. PMID- 28995731 TI - Enteric Fever in Bengal. PMID- 28995732 TI - The Subordinate Medical Department. PMID- 28995733 TI - Lock Hospital Administration in 1870. PMID- 28995735 TI - Scarlet Fever in India. PMID- 28995734 TI - Two Interesting Cases Treated with Hypodermic Injections of Tartar Emetic. PMID- 28995736 TI - Darwinism. PMID- 28995737 TI - East Indian Immigrants in Trinidad. PMID- 28995738 TI - Medical News. PMID- 28995740 TI - The New Merchant Shipping Act. PMID- 28995739 TI - Irritant Causes of Disease. PMID- 28995741 TI - Radical Cure of a Large Ventral Hernia. PMID- 28995742 TI - Remarks on the So-Called Contagious Fever of Our Indian Jails. PMID- 28995743 TI - Meetings of the Bengal Branch of the British Medical Association. PMID- 28995745 TI - Paris Correspondence. PMID- 28995744 TI - Four Cases of Puncture of the Bladder above the Pubis. PMID- 28995747 TI - Supplement to the Indian Medical Gazette. February 1, 1868. PMID- 28995746 TI - Parisnath Sanitarium. PMID- 28995749 TI - The Municipality and the Hospitals. PMID- 28995748 TI - English Correspondence. PMID- 28995750 TI - Outbreak of Epidemic Cholera in the Garrison and District of Kohat, 1867. PMID- 28995751 TI - Summary of Meteorological Observations Taken at the Office of the Civil Assistant Surgeon, Jessore, for the Month of December, 1867. PMID- 28995752 TI - What to Observe on Foreign Service. PMID- 28995753 TI - The Suburban Hospital at Chitpoor. PMID- 28995754 TI - The Progress of the Medical and Collateral Sciences. PMID- 28995756 TI - Extract. PMID- 28995755 TI - Local Correspondence. PMID- 28995758 TI - Extracts. PMID- 28995757 TI - Jeypore. PMID- 28995760 TI - On Insolation. PMID- 28995759 TI - Bengal Medical Retiring Fund. PMID- 28995762 TI - Distribution of Prizes at the Medical College. PMID- 28995761 TI - Aphasia. PMID- 28995763 TI - Case of Chronic Dysentery, with Remarkable Lesion of Mucous Membrane of Stomach. PMID- 28995764 TI - Subordinate Medical Department. PMID- 28995765 TI - Medical Orders. PMID- 28995766 TI - On Cholera. PMID- 28995767 TI - Experiments on the Action of the Cobra Poison. PMID- 28995768 TI - English Correspondence. PMID- 28995769 TI - Notes on Four Cases of Poisoning by Chlorodyne, Treated at the Medical College Hospital, Calcutta, during 1867. PMID- 28995770 TI - Poisoning by Majoon or Majum. PMID- 28995771 TI - List of Medical Officers Who Passed at the Last Competitive Examination for the Three Presidencies in India. PMID- 28995772 TI - On Snake-Poison. PMID- 28995774 TI - Supplement to the Indian Medical Gazette. June 1, 1868. PMID- 28995773 TI - Meetings of the Bengal Branch of the British Medical Association. PMID- 28995775 TI - A Course of Lectures on the Principles and Practice of Medicine, Delivered at the Medical College of Bengal. PMID- 28995776 TI - The Progress of the Medical and Collateral Sciences. PMID- 28995777 TI - Snake-Bite, Cured by Stimulants. PMID- 28995779 TI - The Proposed Medical School at Rangoon. PMID- 28995778 TI - Hemiplegia. PMID- 28995780 TI - English Correspondence. PMID- 28995781 TI - To the Neilgherries and Back. PMID- 28995782 TI - Strychnia. PMID- 28995784 TI - The Eighth Annuity. PMID- 28995783 TI - Mortality Amongst Opium Cultivators. PMID- 28995786 TI - Unlicensed Practitioners. PMID- 28995785 TI - Summary of Fifty Post-Mortem Examinations of Inhabitants of Jessore. PMID- 28995787 TI - Cholera. PMID- 28995788 TI - The Progress of the Medical and Collateral Sciences. PMID- 28995789 TI - Cinchona Cultivation in British Sikkim. PMID- 28995791 TI - Subordinate Medical Department. PMID- 28995790 TI - The Poison of Snakes. PMID- 28995792 TI - Vaccination. PMID- 28995793 TI - Return of Medical Officers Admitted into the Three Presidencies of India, &c. PMID- 28995794 TI - Hermaphroditism. PMID- 28995795 TI - Annual Monthly Rainfall in Berhampore, &c. PMID- 28995796 TI - Weight of the Human Lungs in India. PMID- 28995797 TI - English Correspondence. PMID- 28995798 TI - On Snow-Blindness and Snow-Ophthalmia. PMID- 28995799 TI - Cholera. PMID- 28995800 TI - Ourselves. PMID- 28995801 TI - The Progress of the Medical and Collateral Sciences. PMID- 28995803 TI - To the Neilgherries and Back. PMID- 28995802 TI - Experiments on the Influence of Snake-Poison. PMID- 28995805 TI - Vaccination. PMID- 28995804 TI - Notes on Cinchona Cultivation in British Sikkim (Near Darjeeling). PMID- 28995807 TI - Indigenous Drugs. PMID- 28995806 TI - Cholera. PMID- 28995808 TI - Indian Experience of Lithotrity. PMID- 28995809 TI - Extracts. PMID- 28995810 TI - Poison in Milk. PMID- 28995812 TI - The Medical Charge of Native Regiments. PMID- 28995811 TI - Warrant Medical Officers' Widows' and Orphans' Fund. PMID- 28995814 TI - Insolation. PMID- 28995813 TI - Scurvy in Fort William. PMID- 28995815 TI - Lock Hospitals in Calcutta. PMID- 28995816 TI - Notes on the Malarious Diseases of Pegu. PMID- 28995817 TI - Summary of Fifty Post-Mortem Examinations of Inhabitants of the Jessore District, Performed in the Jail Hospital. PMID- 28995819 TI - Typographical Errors. PMID- 28995818 TI - Cholera. PMID- 28995821 TI - Natural and Physical Science in India. PMID- 28995820 TI - A Port Surgeon for Calcutta. PMID- 28995822 TI - Periodic Hoematuria. PMID- 28995823 TI - Cholera Hospitals. PMID- 28995825 TI - Progress of the Medical and Collateral Sciences. PMID- 28995824 TI - Medico-Legal Notes. PMID- 28995827 TI - English Correspondence. PMID- 28995826 TI - Civil Surgeons in India. PMID- 28995828 TI - Bichloride of Methylene as an Anaesthetic. PMID- 28995829 TI - Application of Ice in the Cure of Sciatica. PMID- 28995830 TI - Experiments on the Influence of Snake-Poison. PMID- 28995831 TI - The Subordinate Medical Department. PMID- 28995832 TI - Primary Amputation of Both Lower Limbs after Railway Injuries. PMID- 28995833 TI - Memorandum of Points to be Studied, Chiefly with the Help of the Microscope, in Postmortem Examinations of Leprosy. PMID- 28995835 TI - Extracts. PMID- 28995834 TI - Cholera. PMID- 28995836 TI - English Correspondence. PMID- 28995837 TI - Snake-Bites.-How to Treat Them. PMID- 28995838 TI - New Furlough Regulations. PMID- 28995839 TI - New Serge Coat for the Artillery. PMID- 28995841 TI - Meetings of the Bengal Branch of the British Medical Association. PMID- 28995840 TI - Antiseptic Dressing. PMID- 28995843 TI - As You Were. PMID- 28995842 TI - Riverside Dispensaries. PMID- 28995845 TI - The Subordinate Medical Department. PMID- 28995844 TI - Experiments on the Influence of Snake-Poison. PMID- 28995846 TI - Progress of the Medical and Collateral Sciences. PMID- 28995847 TI - Case of Abscess in the Brain. PMID- 28995848 TI - An Indian Publishing Medical Society. PMID- 28995849 TI - Bhurtpore Hospital Reports.-No. I. PMID- 28995850 TI - Experiments on the Influence of Snake-Poison. PMID- 28995851 TI - Indian Experiences of Lithotrity.-No. II. PMID- 28995852 TI - Mismanagement. PMID- 28995853 TI - On Cholera.-No. V. PMID- 28995855 TI - English Correspondence. PMID- 28995854 TI - Paucity of Medical Officers. PMID- 28995856 TI - Vernacular Medical Education. PMID- 28995857 TI - Extracts. PMID- 28995858 TI - Difficult Cases in Midwifery, Occurring among Native Women. PMID- 28995860 TI - The Epidemic Cyanosis of Lower Bengal. PMID- 28995859 TI - Insolatio, Considered as a Zymotic Disease. PMID- 28995862 TI - Native Midwifery. PMID- 28995861 TI - Case of Atrophy of the Lungs in a New-Born Infant. PMID- 28995863 TI - Proposed Alterations in the Medical College Hospital. PMID- 28995864 TI - The New Scale of Pay for Uncovenanted Medical Officers in Civil Medical Charge. PMID- 28995865 TI - Statement of Contributions to the Museum of the Medical College, Calcutta, by Medical Officers in the Mofussil, for the Three Months Ending 31st December, 1867. PMID- 28995866 TI - Anaesthetic Leprosy; &c. PMID- 28995867 TI - Official Documents. PMID- 28995868 TI - Meetings of the Bengal Branch of the British Medical Association. PMID- 28995869 TI - Typhoid Fever. PMID- 28995870 TI - Case of Guinea-Worm or Narve, Successfully Treated with Carbolic Acid. PMID- 28995871 TI - English Correspondence. PMID- 28995872 TI - Dislocation Backwards of the Sternal End of the Clavicle. PMID- 28995874 TI - Notes on Ladak in 1867. PMID- 28995873 TI - Supplement to the Indian Medical Gazette. January 1, 1868. PMID- 28995875 TI - The New Sanitary Inspectors-General. PMID- 28995876 TI - The Progress of the Medical and Collateral Sciences. PMID- 28995877 TI - Obstetric Cases. PMID- 28995878 TI - Fibrous Tumour of the Arm, &c. PMID- 28995879 TI - Ourselves. PMID- 28995881 TI - Fracture by Ointment. PMID- 28995880 TI - Stray Notes on Chloroform. PMID- 28995882 TI - Summary of Meteorological Observations Taken at the Office of the Civil Assistant Surgeon, Jessore, for the Month of November, 1867. PMID- 28995884 TI - Paris Correspondence. PMID- 28995883 TI - Practical Remarks on the Treatment of Guinea-Worm. PMID- 28995885 TI - Medical Societies. PMID- 28995886 TI - Four Cases of Chionyphe Carterii (Mucedinous or Fungus Disease of India.). PMID- 28995887 TI - The Treatment of Gonorrhoea by Blistering. PMID- 28995888 TI - Case of Cardiac Embolism. PMID- 28995889 TI - Shealkanta Oil as an External Application for Itch. PMID- 28995890 TI - Ourselves. PMID- 28995891 TI - The Progress of the Medical and Collateral Sciences. PMID- 28995892 TI - Case of Hydrophobia. PMID- 28995893 TI - Syphilization. PMID- 28995894 TI - A Case of Snake-Bite. PMID- 28995896 TI - Good Service Pensions. PMID- 28995895 TI - English Correspondence. PMID- 28995898 TI - Hint from a Hakeem. PMID- 28995897 TI - Amputation of Penis, Etc. PMID- 28995899 TI - Field Surgery with Our Frontier Force. PMID- 28995900 TI - Meeting of the Bengal Branch of the British Medical Association. PMID- 28995901 TI - Supplement to the Indian Medical Gazette. May 1, 1868. PMID- 28995902 TI - The Treatment of Cholera. PMID- 28995903 TI - A Course of Lectures on the Principles and Practice of Medicine, Delivered at the Medical College of Bengal. PMID- 28995904 TI - Extracts. PMID- 28995905 TI - Distribution of Prizes at the Medical College. PMID- 28995906 TI - Extracts. PMID- 28995907 TI - Case of Fatal Melaena. PMID- 28995908 TI - Report of the Outbreak of Cholera at Ajmeer during 1867. PMID- 28995909 TI - A Plea for Hakeems. PMID- 28995910 TI - English Correspondence. PMID- 28995912 TI - "Aide-Memoire," &c., for India. PMID- 28995911 TI - Remarks on the Dry-Earth System of Conservancy. PMID- 28995913 TI - Case of Hepatic Abscess. PMID- 28995914 TI - The Jeypoor Medical School. PMID- 28995915 TI - On the Action of Cobra Poison. PMID- 28995916 TI - State of the Heart in Arsenical Poisoning. PMID- 28995918 TI - Meeting of the Bengal Branch of the British Medical Association. PMID- 28995917 TI - Pathology and Treatment of Coup-De-Soleil or Insolatio. PMID- 28995919 TI - Suburban Hospitals. PMID- 28995920 TI - Amputation of the Penis. PMID- 28995921 TI - Wound of the Spleen. PMID- 28995923 TI - A Burmese Medical Missionary. PMID- 28995922 TI - Cholera in the Bunnoo District in 1867. PMID- 28995924 TI - The Progress of the Medical and Collateral Sciences. PMID- 28995925 TI - On the Action of Cobra Poison. PMID- 28995926 TI - Elephantiasis of Labia Majora and Clitoris Removed and Cured. PMID- 28995927 TI - Supplement to the Indian Medical Gazette. April 1, 1868. PMID- 28995928 TI - Treatment of Dysentery by Native Medicines. PMID- 28995929 TI - Statement of Contributions to the Museum of the Medical College, Calcutta, by Medical Officers in the Mofussil, for the Three Months Ending 31st March, 1868. PMID- 28995930 TI - Rapidly Growing Encephaloid Cancer of the Femur, &c. PMID- 28995931 TI - The Pathology of Hepatic Abscess, Resulting from Dysentery. PMID- 28995932 TI - Horn Growing from the Human Chest. PMID- 28995934 TI - Mr. Fitzgerald's Pamphlet on Cholera. PMID- 28995933 TI - Suspected Criminal Poisoning by Dhatoora. PMID- 28995935 TI - Meetings of the Bengal Branch of the British Medical Association. PMID- 28995936 TI - The Dilution of Vaccine Lymph with Glycerine, &c. PMID- 28995937 TI - Remarks on the So-Called Contagious Fever of Our Indian Jails. PMID- 28995939 TI - Poisoning by Lunar Caustic. PMID- 28995938 TI - Hairy Growth in the Scrotum. PMID- 28995940 TI - Extract. PMID- 28995941 TI - Progress in Jyepore. PMID- 28995943 TI - A Medical Directory for India. PMID- 28995942 TI - The Ooterpara Investigation. PMID- 28995944 TI - Civil Stations in the Central Provinces. PMID- 28995945 TI - English Correspondence. PMID- 28995946 TI - Abscess of the Liver. PMID- 28995947 TI - The Jyepoor Medical School and Maternity Charity. PMID- 28995948 TI - Meteorological Observations. PMID- 28995949 TI - Local Correspondence. PMID- 28995950 TI - Local Correspondence. PMID- 28995951 TI - Supplement to the Indian Medical Gazette. March 2, 1868. PMID- 28995952 TI - The Progress of the Medical and Collateral Sciences. PMID- 28995953 TI - Laceration of the Left Thumb. PMID- 28995955 TI - Vernacular Education in Midwifery. PMID- 28995954 TI - A New Class and Demonstrating Microscope. PMID- 28995956 TI - Local Correspondence. PMID- 28995957 TI - Treatment of Gonorrhoea and Syphilitic Warts. PMID- 28995958 TI - A Suggestion Regarding Post-Partum Haemorrhage. PMID- 28995959 TI - Two Cases of Calculus Vesicae. PMID- 28995960 TI - Experiments on the Action of the Cobra Poison. PMID- 28995961 TI - Improvements in Medical and Surgical Appliances. PMID- 28995962 TI - Subordinate Medical Department. PMID- 28995963 TI - The Progress of the Medical and Collateral Sciences. PMID- 28995964 TI - Introductory Lecture at the Medical College. PMID- 28995965 TI - Abstract of Lithotomy Cases Performed in the Government Charitable Dispensary at Goojerat during the past 27 Months, from 8th December 1865 to 27th March 1868. PMID- 28995966 TI - Supplement to the Indian Medical Gazette. July 1, 1868. PMID- 28995967 TI - New Edition of Dr. Chevers' Medical Jurisprudence for India. PMID- 28995968 TI - Extracts. PMID- 28995969 TI - A Case of Lithotrity. PMID- 28995970 TI - Medical Subordinate Officers' Widows' and Orphans' Fund. PMID- 28995971 TI - English Correspondence. PMID- 28995972 TI - Small-Pox Hospital for Calcutta. PMID- 28995973 TI - Meetings of the Bengal Branch of the British Medical Association. PMID- 28995974 TI - On Cholera. PMID- 28995975 TI - Meteorological Phenomena in India. PMID- 28995976 TI - Compound Comminuted Gun-Shot Fracture of Both Bones of the Forearm. PMID- 28995977 TI - One Year More. PMID- 28995978 TI - On Fatty Degeneration. PMID- 28995980 TI - A Case of Fracture of the Base of Skull by Contrecoup. PMID- 28995979 TI - Case of Haemorrhagic Flux. PMID- 28995981 TI - The Progress of the Medical and Collateral Sciences. PMID- 28995982 TI - Local Correspondence. PMID- 28995983 TI - Summary of Meteorological Observations Taken at the Office of the Civil Assistant Surgeon, Jessore, for the Month of October, 1867. PMID- 28995984 TI - Lectures on Diseases of the Conjunctiva: No. V. PMID- 28995986 TI - Opium-Eating in England. PMID- 28995985 TI - The Lariboisiere and the Medical College Hospitals. PMID- 28995987 TI - Coolie Emigration. PMID- 28995988 TI - Meeting of the Bengal Branch of the British Medical Association. PMID- 28995989 TI - Anaesthetic Leprosy; with Especial Reference to Its Diagnosis and Treatment in the Earlier Stages. PMID- 28995990 TI - Progress of the Medical and Collateral Sciences. PMID- 28995991 TI - A Case of Vicarious Menstruation. PMID- 28995992 TI - Lectures on the Diseases of the Iris. PMID- 28995993 TI - Case of Unusual Susceptibility of the Action of Strychnia. PMID- 28995995 TI - The President of the Asiatic Society. PMID- 28995994 TI - How Service Is Dated. PMID- 28995996 TI - Statement of Contributions to the Museum of the Medical College, Calcutta, by Medical Officers in the Mofussil, for the Three Months Ending 31st March, 1867. PMID- 28995997 TI - Notes on Cases of Functional Paralysis in Children. PMID- 28995998 TI - Correspondence. PMID- 28996000 TI - Extracts. PMID- 28995999 TI - Case of Urethral Calculus. PMID- 28996001 TI - The Training of Medical Missionaries. PMID- 28996002 TI - English Correspondence. PMID- 28996003 TI - Summary of Meteorological Observations Taken at the Office of the Civil Assistant Surgeon, Jessore, for the Month of February, 1867. PMID- 28996004 TI - Notes of a Case of Hooping Cough, with Remarks on Nervous Dyspnoea. PMID- 28996005 TI - Audi Alteram Partem. PMID- 28996006 TI - Contributions to the Cholera Literature. PMID- 28996007 TI - The Health Officer of Calcutta. PMID- 28996008 TI - Chlorodyne in Obstetric Operations. PMID- 28996010 TI - English Correspondence. PMID- 28996009 TI - Destruction of the Eyeball, and an Impetiginous Eruption on the Face Caused by Peripheral Irritation of the Fifth Nerve. PMID- 28996011 TI - Progress of the Medical and Collateral Sciences. PMID- 28996012 TI - Abstract of Lithotomy Cases Performed in the Government Charitable Dispensary, Sealkote, for the Months Commencing from September 1865 to June 1866. PMID- 28996013 TI - Official Documents. PMID- 28996014 TI - Case of Spina Bifida in a Young Man, &c., &c. PMID- 28996015 TI - Summary of Meteorological Observations Taken in the Office of the Civil Assistant Surgeon, Jessore, during the Month of March, 1867. PMID- 28996016 TI - Reports of Meetings of the Bengal Branch of the British Medical Association. PMID- 28996017 TI - Case of Arsenical Poisoning. PMID- 28996018 TI - Poisonous Snakes. PMID- 28996020 TI - The Recent Promotions in the British Medical Service. PMID- 28996019 TI - Case of Ruptured Liver, Spleen, and Kidney, with Fracture of One Arm, &c., &c. PMID- 28996022 TI - The Grievances of Sub-Assistant Surgeons. PMID- 28996021 TI - Notes of a Case of Ovarian Tumour in Which an Exploratory Incision Was Made, &c., &c.; and of a Case in Which Ovariotomy Was Performed with a Successful Result. PMID- 28996023 TI - The Statistical Department. PMID- 28996024 TI - Remarks on the So-Called Contagious Fever of Our Indian Jails. PMID- 28996025 TI - Lectures on Diseases of the Iris-No. II. PMID- 28996026 TI - A Gem of Official Literature. PMID- 28996027 TI - Case of Ascites: With Remarks on Karell's Milk Cure and Thermometrics. PMID- 28996028 TI - Compound Dislocation of Right Femur; Cured. PMID- 28996029 TI - State of the Heart in Arsenical Poisoning. PMID- 28996030 TI - Case of Cholera. PMID- 28996031 TI - Contributions to the Cholera Literature. PMID- 28996033 TI - Progress of the Medical and Collateral Sciences. PMID- 28996032 TI - A Sketch of the Sanitary Arrangements in the Camps Assembled during the Agra Durbar of November 1866. PMID- 28996034 TI - Health in India during 1865. PMID- 28996035 TI - Notes on Some Points Affecting the Diminution in the Rates of Mortality among Europeans in India. PMID- 28996036 TI - Case of Spontaneous Salivation. PMID- 28996037 TI - English Correspondence. PMID- 28996038 TI - Cases from the European General Hospital, Bombay. PMID- 28996040 TI - A New Medical Scheme in the Punjab. PMID- 28996039 TI - On the Endemicity of Cholera in Calcutta. PMID- 28996041 TI - A Case of Intussusception of the Ileum into the Coecum and Ascending Colon; Death; Autopsy. PMID- 28996042 TI - Salus Populi Suprema Lex. PMID- 28996043 TI - Rare Case of "Monster". PMID- 28996044 TI - Ourselves. PMID- 28996045 TI - Extracts. PMID- 28996046 TI - On the Use of Strychnine in the Treatment of Intermittent Fever. PMID- 28996047 TI - Statement of a Case of Chylo-Serous Urine. PMID- 28996048 TI - Midwives' Midwifery. PMID- 28996049 TI - A Case of Idiopathic Tetanus, Successfully Treated with Tincture of Aconite. PMID- 28996050 TI - Summary of Meteorological Observations Taken at the Office of the Civil Assistant Surgeon, Jessore, for the Month of January, 1867. PMID- 28996051 TI - Case of Fibrous Tumour of Upper Jaw; Excision; Recovery. PMID- 28996053 TI - Extract. PMID- 28996052 TI - Local Correspondence. PMID- 28996055 TI - Promotion in the British Medical Service. PMID- 28996054 TI - Lectures on Diseases of the Conjunctiva: No. IV. PMID- 28996056 TI - A Case of Alcoholic Narcotism, with Remarks. PMID- 28996058 TI - Anaesthetic Leprosy; with Especial Reference to Its Diagnosis and Treatment in the Earlier Stages. PMID- 28996057 TI - A Case of Pelvic Cellulitis Causing Retention of Urine. PMID- 28996059 TI - Notes on Ladak in 1867. PMID- 28996061 TI - The Progress of the Medical and Collateral Sciences. PMID- 28996060 TI - Gunshot Wound; Amputation at the Hip-Joint. PMID- 28996062 TI - Paris Correspondence. PMID- 28996063 TI - English Correspondence. PMID- 28996064 TI - Case of Operation for the Restoration of the Nose. PMID- 28996065 TI - Summary of Meteorological Observations Taken at the Office of the Civil Assistant Surgeon, Jessore, for the Month of September, 1867. PMID- 28996066 TI - Abscess of the Liver Successfully Treated by Tapping. PMID- 28996067 TI - The Sanitary Aspect of "Melas." PMID- 28996068 TI - On Ulcus Grave; Morbus Tuberculosis Pedis; Podelkoma; Mycetoma; Madura Foot; or Fungus Foot Disease. PMID- 28996069 TI - Extract. PMID- 28996070 TI - Abstract of Capital and Important Surgical Operations Performed in the Government Charitable Dispensary at Patna, from 1st July 1865 to 30th June 1867. PMID- 28996071 TI - Two Cases of Diabetes. PMID- 28996072 TI - On the Relative Action of the Kidneys in the Cold and Hot Weather of India. PMID- 28996074 TI - Meetings of the Bengal Branch of the British Medical Association. PMID- 28996073 TI - Local Correspondence. PMID- 28996076 TI - English Correspondence. PMID- 28996075 TI - Contributions to the Cholera Literature. PMID- 28996078 TI - Annual Report upon Vaccination at Basein for the Year Ending 31st March, 1867. PMID- 28996077 TI - A Few Notes from Nepaul. PMID- 28996079 TI - Abstract of Lithotomy Operations Performed in the Government Charitable Dispensary at Patna, from 1st July 1865 to 30th June 1867. PMID- 28996080 TI - Sub-Assistant Surgeons in Civil Medical Charge. PMID- 28996081 TI - Results of Endo and Peri-Carditis. PMID- 28996082 TI - Lectures on Diseases of the Conjunctiva: No. I. PMID- 28996083 TI - Dispensary Vaccination. PMID- 28996084 TI - Medico-Legal Notes. PMID- 28996085 TI - Summary of Meteorological Observations Taken at the Office of the Civil Assistant Surgeon, Jessore, for June, 1867. PMID- 28996087 TI - The Progress of the Medical and Collateral Sciences. PMID- 28996086 TI - Local Correspondence. PMID- 28996088 TI - Vernacular Medical Education in Madras. PMID- 28996089 TI - The Appointment of Health Officer in Calcutta. PMID- 28996091 TI - Our Appeal. PMID- 28996090 TI - Cases of Epithelial Cancer of Penis, Treated with Acetic Acid. PMID- 28996093 TI - Dr. Lees' Case of "Spontaneous Evolution." PMID- 28996092 TI - Contributions to the Practice of Midwifery. PMID- 28996094 TI - On the Detection of Dhatoora in Medico-Legal Cases. PMID- 28996095 TI - Progress of the Medical and Collateral Sciences. PMID- 28996096 TI - On Glycerene. PMID- 28996097 TI - An Indian "Medical Agency." PMID- 28996098 TI - Excision of the Os Calcis. PMID- 28996099 TI - Vernacular Medical Education. PMID- 28996100 TI - The Treatment of Hepatic Abscess. PMID- 28996101 TI - Bengal Sanitary Report for 1865. PMID- 28996102 TI - Medical Transport. PMID- 28996103 TI - The Water-Supply of Calcutta. PMID- 28996105 TI - Remarks on Hepatic Abscess. PMID- 28996104 TI - From Landour to the Snowy Range. PMID- 28996106 TI - Notes on Lithotomy. PMID- 28996108 TI - Extracts. PMID- 28996107 TI - Double Rupture of the Heart. PMID- 28996109 TI - Contributions to the Cholera Literature. PMID- 28996110 TI - Regimental Documentary Work. PMID- 28996112 TI - A Peep into Fort William. PMID- 28996111 TI - Animal Radiation: Rough Notes on No. 1 of Dr. Bonavia's "Contributions to the Cholera Literature," in the "Indian Medical Gazette" of Last Month. PMID- 28996113 TI - English Correspondence. PMID- 28996114 TI - Medical Charge of Political Agencies. PMID- 28996115 TI - Case of Complete Absence of Both Rectum and Anus. PMID- 28996116 TI - Paris Correspondence. PMID- 28996117 TI - The Progress of the Medical and Collateral Sciences. PMID- 28996119 TI - Local Correspondence. PMID- 28996118 TI - Case of Sloughing Ulcer Treated by Potassae Chloras. PMID- 28996120 TI - Case of Occlusion of the Vagina. PMID- 28996121 TI - Summary of Meteorological Observations Taken at the Office of the Civil Assistant Surgeon, Jessore, for the Month of July, 1867. PMID- 28996122 TI - Lithotomy; Removal of a Slate Pencil from the Bladder. PMID- 28996123 TI - English Correspondence. PMID- 28996125 TI - Local Correspondence. PMID- 28996124 TI - Local Correspondence. PMID- 28996127 TI - Meetings of the Bengal Branch of the British Medical Association. PMID- 28996126 TI - Lectures on Diseases of the Conjunctiva: No. III. PMID- 28996128 TI - Local Correspondence. PMID- 28996129 TI - Addenda to Remarks on the "Pathology of Hepatic Abscess." PMID- 28996130 TI - Official Documents. PMID- 28996131 TI - Statement of Contributions to the Museum of the Medical College, Calcutta, by Medical Officers in the Mofussil, for the Three Months Ending 30th September, 1867. PMID- 28996132 TI - Two Cases of Fracture of the Skull, Extravasation of Blood, and Laceration of Cerebral Substance, Having Different Symptoms in Each. PMID- 28996133 TI - Mortality among Immigrants to the Tea Districts of Eastern Bengal. PMID- 28996134 TI - Notes on Abyssinia. PMID- 28996135 TI - Bromide of Potassium in Insanity. PMID- 28996136 TI - Paris Correspondence. PMID- 28996137 TI - The New Scale of Pay. PMID- 28996138 TI - Post-Mortem Appearances in a Case of Death by Lightning. PMID- 28996139 TI - Gutta-Percha Tissue. PMID- 28996140 TI - Notes of a Case of Trismus Nascentium. PMID- 28996141 TI - Lectures on Diseases of the Iris.-No. III. PMID- 28996142 TI - English Correspondence. PMID- 28996143 TI - A Move in the Wrong Direction. PMID- 28996144 TI - Abstract of Capital and Important Surgical Operations Performed in the Government Charitable Dispensary at Meerut for 18 Months, from July 1864 to December, 1865. PMID- 28996146 TI - The Goodsir Fellowship. PMID- 28996145 TI - Two Cases of Amputation, Illustrative of the Advantage of Acupressure over Ligature. PMID- 28996148 TI - Lord Napier's Apology. PMID- 28996147 TI - Note on the Action of the Juice of the Leaves and Stalk of Madar (Asclepias Gigantea.). PMID- 28996149 TI - Case of Hepatic Abscess. PMID- 28996151 TI - Extracts. PMID- 28996150 TI - Abstract of Lithotomy Cases Performed in the Government Charitable Dispensary at Meerut, from July 1864 to December 1865. PMID- 28996152 TI - Correspondence. PMID- 28996153 TI - Case of Cystic Disease of Mamma and Ovary; Amputation of the Breast.; Recovery. PMID- 28996154 TI - Correspondence. PMID- 28996155 TI - Secondary Resection of Shoulder-Joint. PMID- 28996156 TI - Contributions to the Cholera Literature. PMID- 28996157 TI - Vaccination in the Punjab. PMID- 28996158 TI - The Progress of the Medical and Collateral Sciences. PMID- 28996159 TI - Case of Cranial Wound, Involving Loss of a Portion of the Occipital Bone; Laceration of Meninges, and Exposure of Brain Substance; Rapid Recovery. PMID- 28996161 TI - Farewell Address to Dr. Francis from the Professors of the Medical College of Bengal. PMID- 28996160 TI - Summary of Meteorological Observations Taken at the Office of the Civil Assistant Surgeon, Jessore, for the Month of April 1867. PMID- 28996162 TI - Vernacular Medical Education. PMID- 28996163 TI - Summary of Meteorological Observations Taken at the Office of the Civil Assistant Surgeon, Jessore, for the Month of July, 1867. PMID- 28996164 TI - Remarks on the Pathology of Hepatic Abscess. PMID- 28996165 TI - English Correspondence. PMID- 28996166 TI - The Goodsir Fellowship. PMID- 28996167 TI - Anaesthetic Leprosy; with Especial Reference to Its Diagnosis and Treatment in the Earlier Stages. PMID- 28996168 TI - Supplement to the Indian Medical Gazette. September 2, 1867. PMID- 28996169 TI - Case of Medullary Tumour of the Arm, &c. PMID- 28996171 TI - Remarks on the Fever Now Prevailing in Mauritius. PMID- 28996170 TI - A Case of Mania Treated Successfully. PMID- 28996172 TI - Paris Correspondence. PMID- 28996173 TI - The Progress of the Medical and Collateral Sciences. PMID- 28996174 TI - Meetings of the Bengal Branch of the British Medical Association. PMID- 28996175 TI - The "Contagious Diseases Act" for India. PMID- 28996176 TI - On the Pathology of Hepatic Abscess as a Result of Dysentery. PMID- 28996178 TI - Official Documents. PMID- 28996177 TI - On the Fungus Foot Disease and Its Treatment. PMID- 28996179 TI - Lectures on Diseases of the Conjunctiva: No. II. PMID- 28996180 TI - Local Correspondence. PMID- 28996181 TI - Medical Titles. PMID- 28996182 TI - The Water Supply of Calcutta. PMID- 28996183 TI - Case of Gonorrhoea, Followed by a Roseolar Eruption, Not Depending on the Use of Copaiba. PMID- 28996184 TI - A Cry for Help. PMID- 28996185 TI - The Minute Anatomy of Muscle, and the Staining Action of Aniline. PMID- 28996186 TI - The Fate of the Salaries Commission Report. PMID- 28996187 TI - Retirement on Reaching a Certain Age. PMID- 28996189 TI - Progress of the Medical and Collateral Sciences. PMID- 28996188 TI - Note on the Treatment of Squamous Diseases of the Skin. PMID- 28996190 TI - Contributions to the Cholera Literature. PMID- 28996191 TI - English Correspondence. PMID- 28996192 TI - Case of Severe Incised Wound; Excision of the Shoulder-Joint; Successful. PMID- 28996193 TI - The Bengal Medical Retiring Fund. PMID- 28996194 TI - A Bad Start. PMID- 28996195 TI - The Work of Deputy Inspectors-General of Hospitals. PMID- 28996196 TI - Linear Extraction. PMID- 28996197 TI - Defamation or No Defamation. PMID- 28996198 TI - Case of Excision of the Os Calcis. PMID- 28996199 TI - Case of Poisoning by Aconite. PMID- 28996201 TI - Extract. PMID- 28996200 TI - A Case of Depressed Fracture of the Skull, in Which a Portion of the Cerebral Substance Escaped; Recovery. PMID- 28996202 TI - A Monster Kidney: Extract from the Half-Yearly Report of the Burrisaul Dispensary Ending 30th June, 1864. PMID- 28996204 TI - The Use of Kousso as an Anthelmintic. PMID- 28996203 TI - 1867. PMID- 28996205 TI - Stray Observations on Stone in the Bladder, and the Taking of It out. PMID- 28996207 TI - The Calcutta Medical College Hospital. PMID- 28996206 TI - Strangulated Hernia Operation, and Subsequent Operation for the Radical Cure. PMID- 28996208 TI - Case of Poisoning by Quinine. PMID- 28996209 TI - Results of Sanitation in India. PMID- 28996210 TI - A Few Notes from Nepaul. PMID- 28996212 TI - How Service Is Dated. PMID- 28996211 TI - A Sketch of the Fevers of Assam. PMID- 28996213 TI - Supplement to the Indian Medical Gazette. July 1, 1867. PMID- 28996214 TI - Case from the European General Hospital, Bombay. PMID- 28996215 TI - English Correspondence. PMID- 28996216 TI - A Case Worthy of Further and More Accurate Investigation. PMID- 28996217 TI - Summary of Meteorological Observations Taken at the Office of the Civil Assistant Surgeon, Jessore, for the Month of May 1867. PMID- 28996218 TI - The Progress of the Medical and Collateral Sciences. PMID- 28996219 TI - Lectures on Diseases of the Iris-No. IV. PMID- 28996220 TI - Local Correspondence. PMID- 28996221 TI - Case of Rabies Canina; Salivation; Recovery. PMID- 28996222 TI - Relapsing Fever in the Shahpore Jail in the Spring of 1867. PMID- 28996224 TI - A Public Medical Library for Calcutta. PMID- 28996223 TI - Female Medical Missions. PMID- 28996225 TI - Abstract of Amputations Performed in the Government Charitable Dispensary at Ajmere, from January 1865 to June 1867; with Remarks. PMID- 28996226 TI - Statement of Contributions to the Museum of the Medical College, Calcutta, by Medical Officers in the Mofussil, for the Three Months Ending 30th June, 1867. PMID- 28996227 TI - The Medical College of Bengal. PMID- 28996228 TI - Case of Worms-Species Unknown-Treated in the City of Nagpoor. PMID- 28996230 TI - Report of Assistant-Surgeons Lewis and D. Cunningham, on Special Duty at the Presidency Connected with the Investigation of Cholera, to the Medical Department, Forwarded to the Government of India in August, 1869. PMID- 28996229 TI - Cases of Poisoned Bites. PMID- 28996231 TI - Medical Administration. PMID- 28996232 TI - On the Relation of Fungi to Disease. PMID- 28996234 TI - Sanitary Reform in Turkey. PMID- 28996233 TI - Remarks on Ozaena. PMID- 28996235 TI - Fatal Case of Idiopathic Tetanus in a European. PMID- 28996237 TI - British Association Committee on the Treatment and Utilisation of Sewage. PMID- 28996236 TI - Traumatic Mydriasis. PMID- 28996239 TI - Transactions of the Medical and Physical Society of Bombay. PMID- 28996238 TI - Dalhousie as a Sanitarium. PMID- 28996241 TI - Extracts. PMID- 28996240 TI - Experiments upon Monkeys with Strychnine. PMID- 28996242 TI - Canals and Sanitation. PMID- 28996243 TI - Mr. Broughton's Researches into the Chemistry of the Cinchonas. PMID- 28996244 TI - The Thanatophidia of India. PMID- 28996246 TI - Calcutta Medical College. PMID- 28996245 TI - Extract from Mr. Broughton's Report to the Madras Government. PMID- 28996247 TI - Epithelioma of the Lower Lip, and Chin, Involving the Lower Jaw on the Left Side of the Symphysis; Removal of the Diseased Parts; Formation of a New Lip and Chin; Asphyxia from the Passage of a Clot into the Larynx with Spasm of the Glottis; Impending Death; Tracheotomy; Recovery. PMID- 28996248 TI - Gangrene of the Integument of the Leg from a Contusion; Fatal Termination Due to Splenic Cachexia and the Formation of Fibrinous Coagula in the Right Side of the Heart. PMID- 28996249 TI - On the Health of Settlers in the Darjeeling Terai. PMID- 28996250 TI - Remarks on Heat Apoplexy. PMID- 28996251 TI - Correspondence. PMID- 28996252 TI - Experiments on Snake Poison. PMID- 28996253 TI - AEther Spary for Internal (Vesical) Haemorrhage. PMID- 28996254 TI - The Thanatophidia of India. PMID- 28996255 TI - Changes in the Service. PMID- 28996256 TI - Nagpore Medical School. PMID- 28996257 TI - Cholera. PMID- 28996259 TI - Extracts. PMID- 28996258 TI - Bite from a Snake Said to Have Been Poisonous; Liquor Ammoniae Treatment; Recovery. PMID- 28996260 TI - The Late Sir James Simpson, Bart. PMID- 28996261 TI - Meteorology of the Punjab for the Years 1867 and 1868. PMID- 28996262 TI - Points of Interest in the Medical History of H. M.'s 58th Regiment during the Last Five Years, with Special Reference to the Advisability of Locating All, or Nearly All, Our European Troops in India on the Mountain Ranges. PMID- 28996264 TI - Correspondence. PMID- 28996263 TI - Correspondence. PMID- 28996265 TI - Case of Smothering. PMID- 28996266 TI - Small-Pox and Vaccination in Bhurtpoor. PMID- 28996267 TI - Native Midwives. PMID- 28996268 TI - Health of the British Troops in the Madras Command, Including British Burmah, for the Year 1868. PMID- 28996269 TI - The Sanitation of the Camp at Calcutta. PMID- 28996270 TI - Progressive Advance in the Health of London. PMID- 28996271 TI - Ventilation in India. PMID- 28996272 TI - Extracts from the Records, Bengal Medical Department. PMID- 28996273 TI - Hyposulphite of Soda in Small-Pox. PMID- 28996274 TI - Extracts. PMID- 28996275 TI - Circular to All Deputy Inspectors-General of Hospitals. PMID- 28996277 TI - Cashmir. PMID- 28996276 TI - Treatment of Intermittent Fever by the Hypodermic Injection of Quinine. PMID- 28996278 TI - The Thanatophidia of India. PMID- 28996279 TI - Dr. Bryden on Cholera. PMID- 28996280 TI - Cinchona and Other Medical Drugs. PMID- 28996282 TI - The Water Supply of Calcutta. PMID- 28996281 TI - Chronic Diarrhoea, &c. PMID- 28996283 TI - Cases of Snake-Bite. PMID- 28996284 TI - Contribution from the Mitford Hospital, Dacca. PMID- 28996285 TI - Excision of the Superior Maxillary Bone. PMID- 28996286 TI - Milk Diet in Disease. PMID- 28996287 TI - Lithotomy. PMID- 28996289 TI - Cinchona Cultivation in Java. PMID- 28996288 TI - Darjeeling. PMID- 28996290 TI - Points of Interest in the Medical History of H. M.'s 58th Regiment during the Last Five Years, with Special Reference to the Advisability of Locating All, or Nearly All, Our European Troops in India on the Mountain Ranges. PMID- 28996291 TI - Extracts. PMID- 28996292 TI - Irish Correspondence. PMID- 28996293 TI - Cod-Liver Cream. PMID- 28996294 TI - A Rare Case. PMID- 28996295 TI - The Bengal Medical Retiring Fund. PMID- 28996296 TI - Experiments on Snake Poison. PMID- 28996297 TI - Modification of Borelli's Operation for Partial Staphyloma of the Cornea. PMID- 28996299 TI - Treatment of Phthisis by Iodide of Potassium. PMID- 28996298 TI - On the Origin of Disease. PMID- 28996300 TI - The Thanatophidia of India. PMID- 28996302 TI - Guinea Worm: Novel Mode of Extraction. PMID- 28996301 TI - A Case of Peenash. PMID- 28996303 TI - The Royal Irish Medical Benevolent Fund Society. PMID- 28996304 TI - Clinical Lecture on Contusion of the Hip. PMID- 28996306 TI - Experiments on Snake Poison. PMID- 28996305 TI - The Value of Quinine. PMID- 28996307 TI - The Morbid Anatomy of Insanity. PMID- 28996309 TI - Vaccination in Scotland. PMID- 28996308 TI - On the Protective Power of Vaccination as Influenced by Change of Climate. PMID- 28996310 TI - Case of Crushed Hand and Fore-Arm; Amputation below the Elbow; Antiseptic Treatment. PMID- 28996311 TI - The Thanatophidia of India. PMID- 28996312 TI - Points of Interest in the Medical History of H. M.'s 58th Regiment during the Last Five Years, with Special Reference to the Advisability of Locating All, or Nearly All, Our European Troops in India on the Mountain Ranges. PMID- 28996313 TI - Microscopic Appearance of the Tumor, &c., Referred to at the Conclusion of Dr. Ewart's Case, Page 131. PMID- 28996314 TI - Case of Erythema Scarlatiniforme. PMID- 28996315 TI - The Medical Charge of the Native Army. PMID- 28996316 TI - Two Cases of Heat Apoplexy. PMID- 28996317 TI - Impetiginous Eruption of the Face Caused by Peripheral Irritation of Branches of the Trigeminal Nerve. PMID- 28996319 TI - Army Medical Service and the Army Estimates. PMID- 28996318 TI - Report on an Outbreak of Cholera on Board the "Edith Moore". PMID- 28996320 TI - The Term "Native Doctor". PMID- 28996321 TI - Contributions from the Mitford Hospital. PMID- 28996322 TI - Extracts from Dr. B. W. Richardson's Lectures on Meteorological Readings in Relation to Surgical Practice. PMID- 28996324 TI - The Madras Monthly Journal of Medical Science. PMID- 28996323 TI - Acute Mania Successfully Treated with Hydrate of Chloral. PMID- 28996326 TI - Scurvy. PMID- 28996325 TI - Vaccination in Ladak in the Years 1868 and 1869. PMID- 28996327 TI - Cholera. PMID- 28996328 TI - Clinical Lecture on Periostitis, &c. PMID- 28996329 TI - Manufacture of the Cinchona Alkaloid in India. PMID- 28996330 TI - Note on Color Blindness. PMID- 28996331 TI - Case of Encephaloid Cancer of the Lungs; Death; Autopsy. PMID- 28996332 TI - Extract from the Report of the Agri-Horticultural Society of the Punjab on Sunflowers. PMID- 28996333 TI - Extracts. PMID- 28996334 TI - Local Correspondence. PMID- 28996335 TI - Remarks on the Temperature, Pulse, and Respirations in Healthy Sepoys. PMID- 28996336 TI - Proceedings of the Bengal Branch of the British Medical Association. PMID- 28996338 TI - Ipecacuanha. PMID- 28996337 TI - Dalhousie as a Sanitarium. PMID- 28996339 TI - Annual Meeting of the Bengal Branch of the British Medical Association. PMID- 28996340 TI - Tempora Mutantur; Nos Non Mutantur in Illis. PMID- 28996341 TI - The Consumption of Horse-Meat in France. PMID- 28996342 TI - Vital Statistics of Melbourne and Suburbs for October 1869. PMID- 28996344 TI - Operative Treatment of Varicose Veins. PMID- 28996343 TI - Vienna Clinique.-The Local Treatment of Croup. PMID- 28996345 TI - The New York School of Medicine. PMID- 28996346 TI - Was It Malarious Fever or Sun-Stroke Cured by Quinine?: Naturam Morborum Remedia Ostendunt. PMID- 28996347 TI - Medullary Cancer of the Lower End of Femur and Head of the Tibia;-Amputation. PMID- 28996348 TI - Protrusion of Lung from a Wound in the Abdomen. PMID- 28996349 TI - The Hyderabad Cholera Statistics. PMID- 28996350 TI - The "Dreadnought," Hospital Ship off Greenwich. PMID- 28996351 TI - Vital Statistics of France. PMID- 28996352 TI - Small-Pox and Vaccination in Bhurtpoor. PMID- 28996354 TI - The Calcutta Tanks. PMID- 28996353 TI - Belladona an Antidote to Opium. PMID- 28996355 TI - Simla as a Sanitarium. PMID- 28996356 TI - The Thanatophidia of India. PMID- 28996357 TI - "Dreadnought," Hospital Ship.-Cases of Scurvy: Reported in the Lancet. PMID- 28996358 TI - Extracts. PMID- 28996359 TI - Irish Correspondence. PMID- 28996360 TI - Notes of a Case of Transposition of the Viscera. PMID- 28996361 TI - St. George's Hospital Medical Cases: Reported in the Lancet. PMID- 28996363 TI - The Origin of Life. PMID- 28996362 TI - The Indications from Tracheotomy in Cases of Laryngitis and Diptheria. PMID- 28996364 TI - Darjeeling. PMID- 28996366 TI - M. Leon Colin on Typhoid Fever. PMID- 28996365 TI - Experiments on Snake Poison. PMID- 28996368 TI - On the Calcutta Drinking Waters the Natural History or Changes in Potable Waters of Tropical Climates, &c. PMID- 28996367 TI - Case of Scarlatina in the Hills. PMID- 28996369 TI - Death from Chloroform. PMID- 28996370 TI - Observations on the Action of Quinine on the Temperature of the Body in Disease. PMID- 28996371 TI - Amputation at the Lower Third of Thigh, by a Long Anterior Flap. PMID- 28996372 TI - Water-Supply at Peshawar. PMID- 28996374 TI - Extracts. PMID- 28996373 TI - A Case without a Name; Diagnosis Required. PMID- 28996375 TI - Death from a Sword Wound. PMID- 28996376 TI - The Thanatophidia of India. PMID- 28996377 TI - Dandies for Field Service. PMID- 28996378 TI - Bright's Disease Treated with Milk. PMID- 28996379 TI - Experiments on the Regeneration of Cartilage. PMID- 28996380 TI - Copaiba in Dropsy. PMID- 28996381 TI - A Case of Peenash. PMID- 28996383 TI - Contributions from the Mitford Hospital. PMID- 28996382 TI - Case of Rupture of the Womb. PMID- 28996384 TI - Deep Sea Explorations. PMID- 28996385 TI - Enlarged Spleen. PMID- 28996386 TI - Lunatics, Idiots, and Cretins in France. PMID- 28996387 TI - The Thanatophidia of India. PMID- 28996388 TI - Saline Treatment of Cholera. PMID- 28996389 TI - Belladonna in Intussusception, and Obstinate Constipation of the Bowels. PMID- 28996390 TI - Extemporaneous Substitute for the Short Forceps in Midwifery. PMID- 28996391 TI - Progress of Cholera. PMID- 28996392 TI - On the Use of Cod Liver Oil in Ulceration of the Cornea, Occurring during Recovery from Severe Cholera, or Low Forms of Disease. PMID- 28996393 TI - Extracts. PMID- 28996394 TI - Ventilation in India. PMID- 28996395 TI - Atelektasis Pulmonium. PMID- 28996396 TI - Dr. C. Macnamara on Cholera. PMID- 28996397 TI - Avoidance of Purgatives, and Employment of Bael Sherbet, When Foreign Bodies, Such as Coins, Buttons, &c., Are Swallowed, Especially by Children. PMID- 28996399 TI - Small-Pox and Vaccination in Holland. PMID- 28996398 TI - Treatment by Pine-Apple Juice and the Salts of Soda and Potash, of a Form of Jaundice of Frequent Occurrence in Bengal. PMID- 28996401 TI - Treatment and Utilisation of Sewage. PMID- 28996400 TI - Ranula: Its Treatment by Iodine. PMID- 28996403 TI - Early Notice of Chloroform. PMID- 28996402 TI - Simla as a Sanitarium. PMID- 28996404 TI - Deputy Inspectors-General of Hospitals. PMID- 28996405 TI - Mode of Dislodging a Calculus Impacted in the Urethra. PMID- 28996406 TI - Sanitary Matters in Holland. PMID- 28996407 TI - Extracts from the Records of the Bengal Medical Department. PMID- 28996408 TI - Case of Bending of the Radius in an Adult. PMID- 28996409 TI - Optic Neuritis-The Result of Malarial Toxaemia. PMID- 28996411 TI - Extracts. PMID- 28996410 TI - Ptyalism as a Symptom of Syphilis. PMID- 28996413 TI - Case of Mussammut Muthree: From the Barielly Female Medical School. PMID- 28996412 TI - Experiments on Snake Poison. PMID- 28996414 TI - Selections from Ophthalmic Surgery. PMID- 28996416 TI - The Most Recent Accounts about Ipecacuanha. PMID- 28996415 TI - A Case of Broken Neck. PMID- 28996417 TI - The Endemic or Epidemic Fever of Lower Bengal. PMID- 28996418 TI - Vital Statistics of the London Police. PMID- 28996420 TI - Darjeeling. PMID- 28996419 TI - A Marine Sanitarium for Calcutta. PMID- 28996421 TI - A Month's Practice in a Small Indian Dispensary. PMID- 28996422 TI - Military Medicine in Prussia. PMID- 28996423 TI - The Thanatophidia of India. PMID- 28996424 TI - Native Midwives. PMID- 28996425 TI - Remarks on Taenia Echinococcus. PMID- 28996427 TI - Military Medicine in France. PMID- 28996426 TI - Reduction of Temperature in Fever. PMID- 28996428 TI - Economics. PMID- 28996429 TI - Points of Interest in the Medical History of H. M.'s 58th Regiment, &c. PMID- 28996430 TI - The Thanatophidia of India. PMID- 28996431 TI - Re-Vaccination. PMID- 28996432 TI - On Recent Improved Methods of Analyses of Potable Waters, and on the Drinking Waters of Calcutta. PMID- 28996433 TI - Extracts. PMID- 28996434 TI - On the Origin of Disease. PMID- 28996435 TI - The New Medical Act. PMID- 28996437 TI - Important Improvement in the Microscope. PMID- 28996436 TI - Case of Malignant Tumour of Right Knee-Joint-Amputation. PMID- 28996438 TI - Lasciate ogni speranza voi che entrate. PMID- 28996439 TI - On the Influence of the Poison of Bungarus Coeruleus or Krait. PMID- 28996441 TI - Anaemia Treated with Milk: Contributed from the Case Book of the General Hospital, Calcutta. PMID- 28996440 TI - Heat Apoplexy Treated with Quinine; Recovery. PMID- 28996442 TI - Paracentesis in Synovitis of the Knee-Joint. PMID- 28996443 TI - On the Influence of Snake-Poison on the Blood. PMID- 28996444 TI - Remarkable Case of Fracture of the Pelvis. PMID- 28996445 TI - On the Use of Dhatura as a Mydriatic. PMID- 28996446 TI - Cysts and Tape-Worms. PMID- 28996447 TI - Persistent Delusions in Small-Pox. PMID- 28996449 TI - The Thanatophidia of India: Deaths by Snake-Bite in the Bengal Presidency during 1869. PMID- 28996448 TI - Incontinence of Urine in Childhood. PMID- 28996450 TI - A Large Hepatic Abscess Tapped and Injected with Carbolic Oil; Convalescence; Sudden Death Four Weeks after the Operation. PMID- 28996451 TI - Supplement to the Indian Medical Gazette, November 1, 1870. PMID- 28996452 TI - Water Supply at Peshawar. PMID- 28996454 TI - Caries of the Tarsal Bones of Left Foot, with Disease of the Joint; Amputation; Successful Result. PMID- 28996453 TI - Fibrous Tumour, of 35 Years' Standing, Occupying the Whole of the Buccal Cavity; Removal; Fatal Result. PMID- 28996456 TI - Extracts. PMID- 28996455 TI - The Medical Administration of the Turkish Army. PMID- 28996457 TI - Cancer of the Pancreas; Simulating Hepatic Abscess; Death; Autopsy. PMID- 28996458 TI - Experiments on Snake Poison. PMID- 28996459 TI - On the Therapeutical Value of Hydrate of Chloral, as a Hypnotic, Anodyne, and Sedative. PMID- 28996460 TI - Two Cases of Vascular Tumor, Treated by Injection with a Saturated Watery Solution of Tannin. PMID- 28996461 TI - Case of Sergeant James Scott, 79th Cameron Highlanders. PMID- 28996462 TI - Observations on the Pathology and Treatment of Cholera. PMID- 28996463 TI - Progress of the Medical Sciences. PMID- 28996464 TI - Great Britain. PMID- 28996465 TI - Some of the Physiological Effects of Quinine. PMID- 28996466 TI - Abscess of Liver Bursting into the Pericardium. PMID- 28996468 TI - Sub-Assistant Surgeons. PMID- 28996467 TI - Clinical Observations on Three Cases of a Form of Hemiplegia: Which Illustrate the Great Importance of Early, Correct Diagnosis; for If Recognized in the Early Stage, It Is Susceptible of Complete Cure; While, If the Diagnosis Is Delayed, or the Proper Treatment Be Not Applied, the Damaged Condition Becomes Permanent, and the Patient Is Doomed to Pass the Remainder of His Life a Cripple. PMID- 28996469 TI - On Science in India. PMID- 28996470 TI - Lecture on Linear Extraction. PMID- 28996471 TI - Our New Sailor's Home. PMID- 28996472 TI - Small-Pox. PMID- 28996473 TI - Practical Observations on European Life in India. PMID- 28996474 TI - Hydrophobia (?). PMID- 28996475 TI - On Linear Extraction. PMID- 28996477 TI - Precis of Medico-Legal Post-Mortem Examinations Made in Dacca during the Year 1865. PMID- 28996476 TI - Extension of Vaccination. PMID- 28996478 TI - Destitution in Calcutta. PMID- 28996479 TI - Ourselves. PMID- 28996480 TI - A Case of Extra-Uterine Gestation. PMID- 28996481 TI - Clinical Observations on a Rare Form of Dysphagia Lately Treated in the General Hospital, Calcutta. PMID- 28996482 TI - Fallen through. PMID- 28996483 TI - Progress of the Medical and Collateral Sciences. PMID- 28996484 TI - Calculus Vesicae in the Female. PMID- 28996485 TI - The Adulterations of Chloroform. PMID- 28996486 TI - Observations on the Pathology and Treatment of Cholera. PMID- 28996487 TI - Notes on Recurrent Mania. PMID- 28996488 TI - Indian Conservancy and Health in Assam. PMID- 28996489 TI - Hydrophobia. PMID- 28996491 TI - Correspondence. PMID- 28996490 TI - Case of Fracture and Displacement Forwards of the Body of 1st Lumbar Vertebra. PMID- 28996492 TI - The Question of Fees. PMID- 28996493 TI - State Sanitation and Municipal Commissions. PMID- 28996494 TI - Remarks on the Treatment of Cholera, with Cases. PMID- 28996495 TI - Cases from Chuckdigee Charitable Dispensary. PMID- 28996496 TI - Vesical Calculus. PMID- 28996497 TI - On the Diarrhoea of Infants. PMID- 28996499 TI - The Chandney Hospital. PMID- 28996498 TI - Horse-Hair Sutures. PMID- 28996501 TI - Our Census and Our Health Statistics. PMID- 28996500 TI - Slow Arsenical Poisoning. PMID- 28996503 TI - The Indian Ethnological Congress. PMID- 28996502 TI - Strictures on Sodomy. PMID- 28996504 TI - Case of Ovarian Dropsy, Treated by Tapping and Injection with Iodine. PMID- 28996505 TI - Good-Service Pensions. PMID- 28996506 TI - Note on Hydrargyrum Cum Creta. PMID- 28996508 TI - A New General Civil Hospital in Calcutta. PMID- 28996507 TI - Abstract of the Half-Yearly Report of the Mitford Hospital at Dacca, for the Half Year Ending June 30th, 1866. PMID- 28996509 TI - The Exalted Star of India. PMID- 28996510 TI - The City of Palaces. PMID- 28996511 TI - The Radical Cure of Hernia by Wood's Method. PMID- 28996512 TI - The Chitpore Hospital. PMID- 28996513 TI - Case of Strangulated, Oblique, Inguinal Hernia; Operation; Recovery. PMID- 28996515 TI - The Mitford Hospital at Dacca. PMID- 28996514 TI - Notes on the Medicinal Properties of the "Thistle-Oil," or Oil Extracted from the Seed of the "Argemone Mexicana". PMID- 28996516 TI - Periodical Orchitis. PMID- 28996517 TI - The Calcutta Nurses' Institution. PMID- 28996519 TI - The Progress of Medical and Collateral Sciences. PMID- 28996518 TI - Extract. PMID- 28996520 TI - On the Action of Ipecacuanha in Dysentery. PMID- 28996521 TI - Case of Penetrating Wound of the Abdomen, with Protrusion of a Portion of the Omentum; Excision and Ligature; Recovery. PMID- 28996522 TI - Cases from the European General Hospital, Bombay. PMID- 28996523 TI - English Correspondence. PMID- 28996524 TI - A Query. PMID- 28996525 TI - A Case of Compound Comminuted Fracture of Both Bones of the Leg, Involving the Ankle-Joint, and Compound Dislocation of the Tarsal Bones of the Foot: Amputation in the Middle of the Limb by the Modified Flap Method Originally Planned and Recommended by Dr. Fayrer, Professor of Surgery, Medical College, Calcutta, in an Article Published in the "Indian Annals of Medical Science". PMID- 28996526 TI - Case of Obstinate Constipation of the Bowels, Treated by Small Doses of Strychnine. PMID- 28996527 TI - Compound Dislocation of the Knee-Joint; Recovery without Amputation. PMID- 28996529 TI - Cholera in the Port. PMID- 28996528 TI - Cases from the Hooghly Emambarah Hospital. PMID- 28996530 TI - The Leisure Hours of a Native Prince. PMID- 28996531 TI - A Case of Albuminuria Cured by Ergot and Iron. PMID- 28996532 TI - Fistula in Perineo, through Which All the Urine Passed, the Urethra Being Impervious an Inch Anterior to It; Operation; Recovery. PMID- 28996534 TI - Professional Etiquette Disregarded in India. PMID- 28996533 TI - Remarks on Malaria and Some of Its Effects. PMID- 28996535 TI - Lecture on Atrophy of the Retina, and Paralysis of the Muscles of the Eyeball, Due to Irritation of the Supra-Orbital Nerve. PMID- 28996536 TI - Indigenous Drugs. PMID- 28996537 TI - Mitford Hospital Reports.-No. I. PMID- 28996538 TI - The Subordinate Medical Department. PMID- 28996539 TI - Softening of Bone; Amputation below the Knee; Recovery. PMID- 28996540 TI - The Cholera Conference. PMID- 28996542 TI - The President of the Sanitary Commission. PMID- 28996541 TI - Case of Stone in the Bladder in a Female Child; High Operation Performed; Recovery. PMID- 28996543 TI - Professor J. Y. Simpson, of Edinburgh. PMID- 28996544 TI - Professional Remuneration. PMID- 28996545 TI - Remarks on Dry Earth Conservancy. PMID- 28996546 TI - Two Cases of Compound Fracture of Both Bones of the Leg, Involving the Ankle Joint; in One Death, and One Recovery. PMID- 28996547 TI - Correspondence. PMID- 28996549 TI - The Calcutta College Hospital. PMID- 28996548 TI - New Medicinal Preparations. PMID- 28996550 TI - Remarks on Rupture of the Rectus Femoris, at Its Connections with the Common Tendon, Complicating Fractures of the Thigh. PMID- 28996551 TI - Correspondence. PMID- 28996552 TI - Correspondence. PMID- 28996553 TI - The Term "Native Doctor." PMID- 28996554 TI - A Case of Melanotic Tumor of Hand, Removed by Amputation at Wrist-Joint. PMID- 28996555 TI - Correspondence. PMID- 28996556 TI - Note on the Use of Bisulphate of Iron and Alumina, and Sulphur, in the Treatment of Dysentery. PMID- 28996557 TI - Simulated Hydrophobia. PMID- 28996558 TI - An Act for the Prevention of Contagious Disease. PMID- 28996559 TI - The Indian Medical Officer. PMID- 28996561 TI - Mitford Hospital, Dacca. PMID- 28996560 TI - Note on the Earthquake Experienced at Patna. PMID- 28996562 TI - Sharks and Bathing Ghats. PMID- 28996563 TI - Aphasia and Death Resulting from Softening in Left Anterior Cerebral Lobe and Cerebellum, Due to Atheromatous Degeneration and Embolism of the Cerebral Arteries. PMID- 28996564 TI - Case of Bronchitis Followed by Symptoms of Phthisis; Recovery. PMID- 28996565 TI - Note on the Action of Ipecacuanha in Dysentery. PMID- 28996566 TI - Case of Horn Growing in the Human Scalp. PMID- 28996567 TI - Rupture of the Duodenum by a Kick; Death. PMID- 28996568 TI - On the Influence of Intestinal Worms in the Causation and Modification of Disease. PMID- 28996570 TI - Analysis of Water in India. PMID- 28996569 TI - A Few Remarks on the Treatment of Delirium Tremens. PMID- 28996572 TI - The New Chitpore Hospital. PMID- 28996571 TI - A Case of Combined Pelvic Haematoma and Pelvic Abscess. PMID- 28996573 TI - Ethnology in India. PMID- 28996574 TI - A Word with Our Friends. PMID- 28996575 TI - Cases of Fracture of Left Humerus, and Dislocation of the Wrist-Joint. PMID- 28996577 TI - The Mitford Hospital, Dacca. PMID- 28996576 TI - Case of Gall Stones Escaping Externally through the Abdominal Parietes. PMID- 28996578 TI - Extracts. PMID- 28996579 TI - Correspondence. PMID- 28996580 TI - Resection of the Knee-Joint. PMID- 28996581 TI - On the Probable Causes of the Sparseness of Population in the Town of Akyab and the Arakan Division Generally. PMID- 28996582 TI - Case of Hydatid Tumour in the Brain. PMID- 28996584 TI - Designation of Army Medical Officers. PMID- 28996583 TI - Poisoning by Chloride of Cadmium; Death. PMID- 28996585 TI - Case of Gunshot Wound. PMID- 28996586 TI - Recto-Vaginal Fistula; Cure. PMID- 28996587 TI - Elephantiasis of Left Leg of Fifteen Years' Duration; Amputation, Only One Vessel Requiring Ligature. PMID- 28996588 TI - Three Cases of Amputation at the Shoulder Joint; Two Recoveries, One Death. PMID- 28996589 TI - A Case of Contraction of the Lower Jaw from Adhesions (Internal) of Twelve Years' Standing. PMID- 28996590 TI - Tumour of the Uterus. PMID- 28996591 TI - Progress of the Medical Sciences. PMID- 28996592 TI - English Correspondence. PMID- 28996593 TI - Case of Popliteal Aneurism, Cured by Combined Pressure and Flexion. PMID- 28996595 TI - The Cholera Congress at Constantinople. PMID- 28996594 TI - Poisoning by Datura (Stramonium)- Recovery. PMID- 28996596 TI - Indian Ethnology. PMID- 28996597 TI - Case of Extraordinary Recovery in a Native. PMID- 28996598 TI - An Hermaphrodite? PMID- 28996600 TI - Extracts from European Journals. PMID- 28996599 TI - Compound Fracture of Left Forearm Successfully Treated by Secondary Amputation at the Shoulder-Joint after Necrosis. PMID- 28996601 TI - The Indian Medical Gazette. PMID- 28996602 TI - A Case of Carious Disease Affecting the Bones of Right Hand-Amputation at the Wrist-Joint.-Recovery. PMID- 28996604 TI - Professional Co-Operation. PMID- 28996603 TI - A Case of Aneurism of the Abdominal Aorta. PMID- 28996605 TI - Abdominal Wounds, with Protusion of the Omentum and Small Intestines.-Recovery. PMID- 28996606 TI - Obscure Cases of Renal Disease. PMID- 28996607 TI - A Case of Carious Disease of Wrist-Joint Treated Successfully by Circular Amputation of the Arm; the Stump Healing by the "First Intention." PMID- 28996608 TI - A Case of Syphilitic Cirrhosis, Considered in Connection with Other Syphilitic Lesions of the Liver. PMID- 28996609 TI - Cases from Practice. PMID- 28996610 TI - Regarding Indian Medical Warrants and Civil Pay. PMID- 28996611 TI - Notes of Cases Treated in the Medical College Hospital. PMID- 28996612 TI - Statement of Fractures Treated in the Calcutta Native Hospital during the Year 1864. PMID- 28996613 TI - Abscess of Spleen.-Recovery. PMID- 28996614 TI - Severe Tiger-Bite.-Recovery. PMID- 28996615 TI - A Case of Atelectasis Pulmonum. PMID- 28996616 TI - Articles. PMID- 28996617 TI - The Actual Cautery in Secondary Haemorrhage. PMID- 28996619 TI - Correspondence. PMID- 28996618 TI - Statistics of Cases of Tetanus Treated in the Medical College Hospital during 1861-62-63 and 64, Showing Its Rates of Mortality and Cure, as Also Its Prevalence, in Different Months and Years. PMID- 28996620 TI - Sub-Assistant Surgeons. PMID- 28996621 TI - Case of Lithotomy. PMID- 28996622 TI - Abstract of Lithotomy Cases Treated in the Calcutta Native Hospital during the Years 1863-64-65. PMID- 28996623 TI - Correspondence. PMID- 28996624 TI - The Medical Retiring Fund. PMID- 28996625 TI - Progress of the Medical and General Sciences. PMID- 28996626 TI - Professional Remuneration, &c., in Madras. PMID- 28996627 TI - On the Gratuitous, Compulsory Attendance of Indian Military Doctors in Ordinary Cases of Midwifery. PMID- 28996628 TI - Two Cases of Fracture. PMID- 28996629 TI - Notes and Queries. PMID- 28996630 TI - Lithotomy. PMID- 28996632 TI - The Medical Act. PMID- 28996631 TI - On Leprosy. PMID- 28996633 TI - The Question of "Physic." PMID- 28996634 TI - Extracts. PMID- 28996635 TI - On Emetina, as a Substitute for Ipecacuanha. PMID- 28996636 TI - Correspondence. PMID- 28996637 TI - Ethnology of the Chuas of Shawdowla Temple, Goojrat, Punjab. PMID- 28996638 TI - Cases of Cholera, Tetanus, and Calculus Vesicae. PMID- 28996640 TI - Cinchona Alkaloids. PMID- 28996639 TI - Case of Jackal-Bite. PMID- 28996641 TI - Mitford Hospital Reports.-No. II. PMID- 28996643 TI - Annual Health Report of Calcutta for 1865. PMID- 28996642 TI - Cases from the City Dispensary at Moorshedabad. PMID- 28996644 TI - Professional Courtesy. PMID- 28996645 TI - A Case of Turning; Recovery. PMID- 28996646 TI - The Microscope. PMID- 28996647 TI - Note on the Use of the Powder of Mudar, as a Perfect Substitute for Ipecacuanha, in the Treatment of Acute Dysentery in Natives. PMID- 28996648 TI - Vesical Calculus. PMID- 28996649 TI - Case of "Spontaneous Evolution." PMID- 28996651 TI - Cases from the European General Hospital, Bombay. PMID- 28996650 TI - Corrigendum. AB - [This corrects the article on p. 301 in vol. 1.]. PMID- 28996652 TI - Glaucoma. PMID- 28996654 TI - Ourselves. PMID- 28996653 TI - Some Further Remarks upon Asthenic Hepatic Abscess, with Case. PMID- 28996656 TI - Extract. PMID- 28996655 TI - Case of Amputation below the Knee; Secondary Haemorrhage; Recovery. PMID- 28996657 TI - Case of Extraordinary Susceptibility of the Action of Strychnia. PMID- 28996658 TI - Correspondence. PMID- 28996659 TI - The Education of Dhyes or Native Midwives. PMID- 28996660 TI - Correspondence. PMID- 28996661 TI - Dispensary Vaccination in the Punjab. PMID- 28996662 TI - Correspondence. PMID- 28996663 TI - Mitford Hospital Reports.-No. V. PMID- 28996664 TI - Congres Medical International De Paris: Statuts Et Programme. PMID- 28996665 TI - The New Administrative Staff. PMID- 28996666 TI - English Correspondence. PMID- 28996667 TI - Case of Ovariotomy. PMID- 28996668 TI - Biliary Coma in the Sixth Month of Pregnancy. PMID- 28996670 TI - Correspondence. PMID- 28996669 TI - International Medical Congress. PMID- 28996672 TI - Tertiary Amputation in a Case of Gunshot Wound of the Forearm; Recovery. PMID- 28996671 TI - Cholera in the Port. PMID- 28996673 TI - Indigenous Drugs. PMID- 28996675 TI - The Bengal Branch of the British Medical Association. PMID- 28996674 TI - Case of Supra-Pubic Lithotomy. PMID- 28996677 TI - Medical Fees in India. PMID- 28996676 TI - Case of Penetrating Wound of the Abdomen with Protrusion of a Large Portion of the Pancreas; Its Removal by Ligature; Recovery. PMID- 28996678 TI - Case of Aphasia. PMID- 28996679 TI - Two Successful Cases of Turning, Occurring within a Fortnight of Each Other. PMID- 28996680 TI - Action of Ipecacuanha in Dysentery. PMID- 28996681 TI - The Progress of Medical and Collateral Sciences. PMID- 28996683 TI - The Howrah General Hospital. PMID- 28996682 TI - Correspondence. PMID- 28996684 TI - Proposed Removal of the Medical College Hospital. PMID- 28996685 TI - Case of Necrosis of the Lower Part and Posterior Half of the Humerus. PMID- 28996686 TI - The Calcutta Medical College. PMID- 28996687 TI - Mitford Hospital Reports.-No. III. PMID- 28996688 TI - The New Calcutta Pauper Hospital. PMID- 28996689 TI - Designation of Army Medical Officers. PMID- 28996690 TI - Success versus Truth. PMID- 28996692 TI - English Correspondence. PMID- 28996691 TI - Case of Chronic Hydrocephalus; Recovery by Tapping. PMID- 28996693 TI - Case of Simple Dislocation of the Astragalus. PMID- 28996694 TI - Cases of Craniotomy and Forceps. PMID- 28996696 TI - The Bengal Medical Retiring Fund. PMID- 28996695 TI - On the Probable Causes of the Sparseness of Population in the Town of Akyab and the Arakan Division Generally. PMID- 28996697 TI - Remarks on Cholera. PMID- 28996699 TI - Correspondence. PMID- 28996698 TI - Practical Observations on the Means of Detecting Dhatoora, When It Has Been Administered to Human Beings with the Intention of Inducing Stupefaction, Intoxication, or Death. PMID- 28996700 TI - Ipecacuanha in Dysentery. PMID- 28996701 TI - The Fyzabad Dispensary. PMID- 28996702 TI - On Some Peculiar Effects Observed from the Use of the Indian Hemp. PMID- 28996703 TI - Observations on a Case of Aphasia, or Loss of Speech, Connected with Disease of the Anterior Lobe of the Right Side of the Brain. PMID- 28996705 TI - Cardiac Embolism. PMID- 28996704 TI - Vital Statistics-Census in India. PMID- 28996706 TI - A Shadow of Good Things to Come. PMID- 28996707 TI - Spectral Analysis. PMID- 28996708 TI - Delhi Sores. PMID- 28996709 TI - Scurvy. PMID- 28996710 TI - On Protrusion of the Pancreas through an Abdominal Wound. PMID- 28996711 TI - Hydrargyrum Cum Creta. PMID- 28996712 TI - Report on Two Outbreaks of Epidemic Cholera in the Balasore Jail in March, April, May, and June, 1866. PMID- 28996713 TI - A Query. PMID- 28996715 TI - Treatment of Fever by Cobwebs. PMID- 28996714 TI - State of the Heart in Arsenical Poisoning. PMID- 28996716 TI - Acetic Acid in Cholera. PMID- 28996717 TI - A Young Assistant-Surgeon's Grievance. PMID- 28996718 TI - Case of Protrusion of the Pancreas. PMID- 28996719 TI - Hydrargyrum Cum Creta. PMID- 28996720 TI - Remarks on Travelling in India, and the Influence It Has on the Health of Young Children. PMID- 28996721 TI - On the Detection of Dhatoora. PMID- 28996722 TI - The Pay of Native Doctors. PMID- 28996723 TI - English Correspondence. PMID- 28996724 TI - The Progress of Medical and Collateral Sciences. PMID- 28996725 TI - Sub-Assistant Surgeons. PMID- 28996726 TI - Extracts. PMID- 28996727 TI - Clerical Surgery in India. PMID- 28996728 TI - Idiosyncrasies. PMID- 28996729 TI - On the Communicability of Cholera. PMID- 28996731 TI - On Dhyes or Native Midwives. PMID- 28996730 TI - Suggestions for the Systematic Study of the History and Relations of Cholera. PMID- 28996733 TI - Our Pauper Hospitals. PMID- 28996732 TI - Importance of Fatty Degeneration of the Liver as a Predisposing Cause of Abscess. PMID- 28996735 TI - Case of Difficult Child Delivery. PMID- 28996734 TI - Cases of Excision of the Lower Jaw. PMID- 28996736 TI - Further Remarks on Penetrating Wound of the Abdomen, with Protrusion of the Pancreas. PMID- 28996738 TI - Progress of the Medical and Allied Sciences. PMID- 28996737 TI - Case of Compound Fracture of Hand; Softening of Bones about Elbow-Joint; Conversion of Muscles around Joint into Adipocere; Amputation of Arm; Recovery. PMID- 28996739 TI - Cases of Lithotomy Performed at the Saharunpore Dispensary during the Half-Year Ending June 30th, 1866. PMID- 28996740 TI - The Medical Retiring Fund. PMID- 28996741 TI - Notes on Some of the Diseases Most Frequently Met with among the Natives of Tirhoot. PMID- 28996742 TI - Case of False Traumatic Aneurism of the Femoral Artery, Complicated with General Anasarca and Subsequent Serious Haemorrhage, Cured by Ligature of the Main Trunk. PMID- 28996743 TI - On Cobweb as a Remedy for Malarious Fevers. PMID- 28996744 TI - Obstetric Cases. PMID- 28996745 TI - The Crystalline Lens. PMID- 28996747 TI - A Case of Traumatic Tetanus, with Anoesthesia of the Trunk and Upper Extremities, Treated Successfully. PMID- 28996746 TI - Remarks on Bindaal, a New Remedy in the Treatment of Spleen Diseases. PMID- 28996748 TI - Strychnine in Fever. PMID- 28996750 TI - A Case of Compound Comminuted Fracture of Right Femur, with Some Laceration of the Soft Parts; Recovery without the Performance of Amputation. PMID- 28996749 TI - Ipecacuanha versus Koorchee in Dysentery. PMID- 28996752 TI - Poisoning and Medical Evidence. PMID- 28996751 TI - Mitford Hospital Reports.-No. IV. PMID- 28996753 TI - Cases from Umritsur Charitable Dispensary. PMID- 28996754 TI - Extract. PMID- 28996755 TI - A Lock Hospital for Calcutta. PMID- 28996757 TI - On the Detection of Dhatoora. PMID- 28996756 TI - Hindustani Examinations: Caution to Junior Assistant-Surgeons. PMID- 28996758 TI - Ulceration of the Larynx in a Case of Leprosy; OEdema Glottidis; Laryngotomy. PMID- 28996759 TI - English Correspondence. PMID- 28996760 TI - Horn Growing from the Human Body. PMID- 28996761 TI - Correspondence. PMID- 28996762 TI - On the Use of Arsenic in Periodic and Skin Diseases. PMID- 28996763 TI - Case of Penetrating Wound of the Chest and Abdomen, with Protrusion Ofo Mentum, Simulating Pancreas. PMID- 28996764 TI - Case of Compound Fracture of the Knee-Joint; Excision; Recovery. PMID- 28996765 TI - Remarks on Hepatic Abscess. PMID- 28996766 TI - On McDougall's Disinfecting Powder. PMID- 28996767 TI - Correspondence. PMID- 28996768 TI - Etiology of Epithelioma among the Kashmiris. PMID- 28996770 TI - The Future of the Bengal Medical Retiring Fund. PMID- 28996769 TI - Strangulated Hernia. PMID- 28996771 TI - Reorganization of the Administrative Staff of the British and Indian Medical Services. PMID- 28996772 TI - Remarks on Hepatic Abscess. PMID- 28996773 TI - On the Minute Anatomy of Muscle. PMID- 28996774 TI - Worm in the Eye:-A Contribution to Equine Surgery. PMID- 28996775 TI - A Case of Poisoning by Sheth Kurrubbee, the White Oleander. PMID- 28996776 TI - Ipecacuanha in Dysentery. PMID- 28996777 TI - The Study of Idiosyncrasies. PMID- 28996779 TI - Treatment of Cholera with Acetic Acid. PMID- 28996778 TI - A Case of Fibro-Cartilaginous Tumour of the Left Upper Jaw-Bone; Excision & Cure. PMID- 28996780 TI - In-Growing of the Toe-Nail. PMID- 28996782 TI - Physiological Idiosyncrasies. PMID- 28996781 TI - Remarks on a Case of Abdominal Wound with Protrusion of the Pancreas. PMID- 28996783 TI - Extracts from the Annual Report on the Working Party of the 79th Cameron Highlanders, during the Hot Season of 1865. PMID- 28996785 TI - Extracts. PMID- 28996786 TI - The Progress of Medical and Collateral Sciences. PMID- 28996784 TI - Dysentery. PMID- 28996787 TI - Penetrating Wound of the Abdomen, with Protrusion of the Tail of the Pancreas. PMID- 28996788 TI - Competition. PMID- 28996789 TI - Bengal Jails and Their Superintendents. PMID- 28996791 TI - Notes on Arsenical Poisoning. PMID- 28996790 TI - A Case of Penetrating Wound of the Abdomen and Thorax. PMID- 28996792 TI - Dangers of Eighth Labours. PMID- 28996793 TI - Our Knowledge of Cholera. PMID- 28996794 TI - Cobwebs in Cases of Intermittent Fever. PMID- 28996795 TI - Famine. PMID- 28996796 TI - The Colour for a Studio. PMID- 28996797 TI - Case of Supra-Public Lithotomy. PMID- 28996798 TI - English Correspondence. PMID- 28996799 TI - Epidemic Small-Pox and Vaccine Protection. PMID- 28996801 TI - How Goes It with British Soldiers at 8,000 Feet above Sea-Level? PMID- 28996800 TI - On the Use of Strychnine in the Treatment of Malarious Fevers. PMID- 28996802 TI - Cases of Atelektasis Pulmonum. PMID- 28996805 TI - Case of Perforating Wound of the Abdomen. PMID- 28996804 TI - Effects of "Cannabis Sativa." PMID- 28996803 TI - Wood's Operation for the Cure of Hernia. PMID- 28996807 TI - The Exalted Star of India. PMID- 28996806 TI - Case of Calculus Vesicae: Lithotomy; Tetanus; Alarming Symptoms of Dyspnoea; Coma and Death. PMID- 28996808 TI - The Pathology and Treatment of Cholera. PMID- 28996809 TI - Case of Intermittent Fever. PMID- 28996810 TI - Ergot of Rye and Indian Hemp in Obstinate Cases of Menorrhagia. PMID- 28996812 TI - On the Diarrhoea of Infants. PMID- 28996811 TI - Medicine for Leprosy. PMID- 28996814 TI - Transliteration versus Translation. PMID- 28996813 TI - An Address Delivered on the Occasion of the Distribution of Prizes at the Medical College, Calcutta, at the Close of Session 1872-73. PMID- 28996815 TI - A Case of Nasal Calculus. PMID- 28996817 TI - Water-Supply of Bombay Towns and Villages. PMID- 28996816 TI - Case of Hydatid Cysts Found in the Brain, &c. PMID- 28996819 TI - The Macnamara Filter. PMID- 28996818 TI - Medical News. PMID- 28996820 TI - Our Relations to Government. PMID- 28996821 TI - Thermic Fever. PMID- 28996822 TI - Further Observations on the Epidemic Fever of Burdwan. PMID- 28996823 TI - Memorandum of the Identification of Blood Stains. PMID- 28996824 TI - Malingering in the Native Army. PMID- 28996825 TI - On the Use of a Reflector in the Treatment of Diseases of the Uterus. PMID- 28996826 TI - Cholera. PMID- 28996827 TI - Lithotomy. PMID- 28996829 TI - The Cause of the Burdwan Fever. PMID- 28996828 TI - Rough Notes on the Common Forms of Skin Disease Met with in Calcutta. PMID- 28996830 TI - The Calcutta Medical College. PMID- 28996831 TI - Report on Cholera in the Sagar Circle of Medical Administration during the Year 1872. PMID- 28996833 TI - A Writer for Civil Surgeons. PMID- 28996832 TI - Fragmentary Remarks on New and Old Medicine. PMID- 28996834 TI - On the Etiology and Hygiene of Cholera. Part II. PMID- 28996836 TI - Cultivation of Ipecacuanha. PMID- 28996835 TI - Urinary Fistula with Loss of Much Adjacent Tissues Laying Bare the Roof of the Parineal Portion of the Urethra; Urethro-Plasty: Cure. PMID- 28996837 TI - Lock-Hospitals in the Madras Presidency. PMID- 28996839 TI - Medical News. PMID- 28996838 TI - On a Cystic Parasite Infesting Sheep. PMID- 28996840 TI - Cases of Small-Pox Treated with Sulphuret of Calcium Solution. PMID- 28996841 TI - Report on Cholera in the Hoshungabad District during 1871-72. PMID- 28996842 TI - Elephantiasis Preputialis. PMID- 28996843 TI - The New Indian Medical Warrant. PMID- 28996845 TI - A Dispensary for Russapugla. PMID- 28996844 TI - On the Treatment of Conical Cervix Uteri. PMID- 28996846 TI - Lithotomy. PMID- 28996847 TI - A Case of Poisoning by Opium; Recovery after the Use of Sulphate of Atropia, as a Subcutaneous Injection. PMID- 28996848 TI - Remarks on Dr. Lyons' "Treatise on Relapsing or Famine Fever." PMID- 28996849 TI - Mortuary Registration in Bengal. PMID- 28996851 TI - Mortality among Tea Coolies. PMID- 28996850 TI - Report on an Outbreak of Fever (Miliaria?) at Seoni. PMID- 28996852 TI - Calcutta "Bustees". PMID- 28996853 TI - Calculous in the Bladder; Abscess of Kidneys; Death. PMID- 28996854 TI - Dr. L. Boehm on Cholera. PMID- 28996855 TI - Haepatic Abscess in Natives. PMID- 28996856 TI - Cholera. PMID- 28996857 TI - Report on the Outbreak of Cholera in the Julpigoree District in 1872-73. PMID- 28996858 TI - Ainhum. PMID- 28996859 TI - On Some Prominent Fallacies in Epidemiology. PMID- 28996860 TI - Cases and Observations. PMID- 28996861 TI - Medical Fees. PMID- 28996862 TI - Cases from Practice. PMID- 28996864 TI - Malarial Fever. PMID- 28996863 TI - Rough Notes on the Common Forms of Skin Disease Met with in Calcutta. PMID- 28996865 TI - List of Vernacular Medical Publications. PMID- 28996866 TI - Remarks on the Vaporization of Carbolic Acid as an Air Purifier and Disinfectant. PMID- 28996867 TI - Cases from Practice. PMID- 28996868 TI - On Some Prominent Fallacies in Epidemiology. PMID- 28996869 TI - Report on the Recent Epidemic of Fever in the Rawulpindee Jail. PMID- 28996870 TI - Cases and Observations. PMID- 28996871 TI - Lithotomy. PMID- 28996872 TI - Post-Mortem Notes of Three Cases of Judicial Hanging. PMID- 28996874 TI - Death-Rate of European Soldiers. PMID- 28996873 TI - Lord Lawrence on the Double Medical Administration. PMID- 28996875 TI - Three Cases of Antiseptic Surgery. PMID- 28996877 TI - Medical News. PMID- 28996876 TI - Remarks on Dr. Lyons' "Treatise on Relapsing or Famine Fever." PMID- 28996879 TI - Cholera Precautions. PMID- 28996878 TI - Dr. L. Boehm on Cholera. PMID- 28996880 TI - Memorial by the Sub-Assistant Surgeons in the N. W. Provinces. PMID- 28996881 TI - Famine and Fever, as Cause and Effect in Rajpootana in 1868 and 1869. PMID- 28996883 TI - Remarks on Dieting Sepoys in Hospital. PMID- 28996882 TI - Case of Death from Division of the Spinal Cord in the Neck. PMID- 28996884 TI - Cholera. PMID- 28996885 TI - Cases from Practice. PMID- 28996886 TI - The Causation of the Burdwan Fever. PMID- 28996887 TI - The Recently-Promoted Surgeons-Major of the British Medical Service. PMID- 28996888 TI - The Burdwan Fever. PMID- 28996890 TI - Notes from Practice. PMID- 28996889 TI - The Abuse of Patronage. PMID- 28996891 TI - Malaria. PMID- 28996892 TI - The Indian Locust. PMID- 28996893 TI - Liebrich's Operation for Cataract. PMID- 28996894 TI - Cholera. PMID- 28996895 TI - Local and General Enquiries. PMID- 28996896 TI - Extracts from a Diary Kept during a Visit to Burdwan in September 1873. PMID- 28996898 TI - Emigration. PMID- 28996897 TI - Typhus Fever in Lower Bengal. PMID- 28996899 TI - The Sealdah Vernacular Medical School. PMID- 28996900 TI - Notes on a Form of Sloughing Phagedoena, Prevalent at Indore and Its Vicinity. PMID- 28996901 TI - A Case of Delirium Tremens Simulating Hydrophobia. PMID- 28996902 TI - Case of Madura Foot-Mycetoma. PMID- 28996903 TI - ? AB - [This corrects the article on p. 302 in vol. 8.]. PMID- 28996904 TI - Medical News. PMID- 28996905 TI - So-Called Typhus Fever in the Rawalpindee Jail. PMID- 28996906 TI - Tetanus Resulting from Retained Placenta until Putrid, in a Young Woman Miscarried in Her Third Month: Recovery. PMID- 28996907 TI - A Case of Enteric Fever. PMID- 28996908 TI - Report on the Recent Epidemic of Fever in the Rawalpindee Jail. PMID- 28996909 TI - Old Notes on Malarial Fevers and Cognate Ailments. PMID- 28996910 TI - Report on the Burdwan Fever for the Year 1872; and the Measures Adopted for the Relief of the Sick. PMID- 28996911 TI - Selections from Cases Treated during 1872. PMID- 28996912 TI - On the Mode of Action of Some of the Essential Oils in the Cure of Gripes. PMID- 28996913 TI - Case of Strangulated Hernia. PMID- 28996914 TI - Cases from Practice. PMID- 28996915 TI - "Primitive Belief" as to Propagation of Cholera. PMID- 28996916 TI - On Some Prominent Fallacies in Epidemiology. PMID- 28996918 TI - Simple Continued Fever. PMID- 28996917 TI - A Case of Carbolic Acid Poisoning. PMID- 28996919 TI - Case of Bite of Cobra: Recovery. PMID- 28996920 TI - Notes on an Outbreak of Remittent Fever in the District of Backergunge. PMID- 28996921 TI - Notes on Some Points Connected with Fungus Foot Disease. PMID- 28996923 TI - Does Cholera Attack Horses? PMID- 28996924 TI - Sedative Treatment of Cholera. PMID- 28996922 TI - On Sick Sepoys. PMID- 28996926 TI - Tea Garden Hospitals. PMID- 28996925 TI - Dr. Parkes on Sanitary Progress. PMID- 28996927 TI - Cases from Practice. PMID- 28996928 TI - Notes of a Case of Cholera Treated by the Hypodermic Injection of Chloral Hydrate. PMID- 28996929 TI - On a Mode of Poisoning by Insertion of the Poison into the Subcutaneous Tissue. PMID- 28996931 TI - The Liability of Young Children to Cholera. PMID- 28996930 TI - Report on the Burdwan Fever for the Year 1872; and the Measures Adopted for the Relief of the Sick. PMID- 28996932 TI - The Burdwan Fever. PMID- 28996933 TI - Cholera. PMID- 28996934 TI - Report on the Recent Epidemic of Fever in the Rawalpindee Jail. PMID- 28996935 TI - Extracts from a Diary Kept during a Visit to Burdwan in September 1873. PMID- 28996936 TI - Four Cases of Elephantiasis in the European, Recurrence of Scrotal Tumour after Operation. PMID- 28996937 TI - Contemporary Medical Superstitions. PMID- 28996939 TI - Typhus Fever in Lower Bengal. PMID- 28996938 TI - A Case of Typhoid Fever. PMID- 28996941 TI - Medical News. PMID- 28996940 TI - Two Cases of Snake-Bite Treated by Injection of Liquor Ammoniae into the Veins, with Remarks on the Action of Snake Poison. PMID- 28996942 TI - Simple Continued Fever. PMID- 28996943 TI - On Some Prominent Fallacies in Epidemiology. PMID- 28996944 TI - A Case of Amputation at the Hip-Joint. PMID- 28996945 TI - A Medical School for Burmah. PMID- 28996946 TI - The Effect of Hard Labor and Strict Discipline on the Mortality of Jails. PMID- 28996947 TI - Reports from Practice. PMID- 28996948 TI - A Case of Snake-Bite; Cure. PMID- 28996949 TI - Medical News. PMID- 28996950 TI - Cholera. PMID- 28996951 TI - Marsh Fever Produced by Obstruction of the Outlets of Sub-Soil Water. PMID- 28996952 TI - Re-Organization of the Indian Medical Department. PMID- 28996953 TI - An Aid to Vaccination. PMID- 28996954 TI - Two Cases of Snake-Bite Treated by Injection of Liquor Ammoniae into the Veins, with Remarks on the Action of Snake Poison. PMID- 28996955 TI - Case of Poisoning by Fungi. PMID- 28996957 TI - Malaria. PMID- 28996956 TI - Report on the Recent Epidemic of Fever in the Rawul Pindee Jail. PMID- 28996958 TI - Case of Arrow Wound. PMID- 28996959 TI - Cases from Practice. PMID- 28996960 TI - Bengal Medical Retiring Fund. PMID- 28996961 TI - A Case of Post-Mortem Delivery. PMID- 28996963 TI - The Value of European Life in India. PMID- 28996962 TI - On the Temperature in Health. PMID- 28996964 TI - On Some Prominent Fallacies in Epidemiology. PMID- 28996965 TI - Vernacular Medical Education in Bengal. PMID- 28996967 TI - Vital Statistics in India. PMID- 28996966 TI - The Ceylon Medical School. PMID- 28996969 TI - Dr. Henderson's "Lahore to Yarkand". PMID- 28996968 TI - Milk and Disease. PMID- 28996970 TI - Case of OEdema of the Glottis. PMID- 28996971 TI - Precaution against the Infection of Cholera. PMID- 28996972 TI - Safe Passage of a "Ghungree" through the Intestines of a Child Aged Four Years. PMID- 28996973 TI - Famine and Fever as Cause and Effect in Rajpootana in 1868 and 1869. PMID- 28996974 TI - Lithotomy. PMID- 28996975 TI - Mortuary Registration in Bengal. PMID- 28996976 TI - Case of Encephaloid Disease of the Inguinal Glands; Simulating Aneurism of the External Iliac Artery. PMID- 28996977 TI - Elephantiasis of the Female External Generative Organs. PMID- 28996978 TI - Effusion into the Pericardium in Strangulation. PMID- 28996979 TI - The Heart, in a Case of Poisoning by Arsenic. PMID- 28996980 TI - Case of Fracture of Both Os Calcis. PMID- 28996982 TI - The Burdwan Fever. PMID- 28996981 TI - Suggestions as to the Cause of Unhealthiness of Lower Bengal and the Recent Outbreak of Epidemic Fever. PMID- 28996984 TI - Sepoys in Hospital. PMID- 28996983 TI - Case of Compound Fracture of Femur. PMID- 28996985 TI - Case of Fracture of the Base of the Skull. PMID- 28996986 TI - Classification of Tumours. PMID- 28996987 TI - Eight Persons Suffocated in a Railway Waggon. PMID- 28996988 TI - Jolly on the Dangers of Chloral Hydrate. PMID- 28996989 TI - Report on Cholera in the Gujranwala District for 1872. PMID- 28996990 TI - Report on the Epidemic of Dengue in the Dacca District during 1872. PMID- 28996991 TI - Medical News. PMID- 28996992 TI - Water-Supply for Nagpore. PMID- 28996993 TI - Action of Mercury on the Liver. PMID- 28996994 TI - Water-Supply of British Troops. PMID- 28996996 TI - Veratrum Viride in Haemorrhage and Aneurism. PMID- 28996995 TI - Fragmentary Remarks on New and Old Medicine. PMID- 28996998 TI - Recent Sanitary Legislation in England. PMID- 28996997 TI - Correspondence. PMID- 28997000 TI - Cholera in Calcutta during the Year 1872. PMID- 28996999 TI - The Propagation of Enteric Fever. PMID- 28997001 TI - The Re-Organization of the Indian Medical Department. PMID- 28997002 TI - Two Rare Cases of Stone. PMID- 28997003 TI - On Compulsory Vaccination. PMID- 28997005 TI - Medical News. PMID- 28997004 TI - Emigration. PMID- 28997006 TI - Abstract of a Lecture on the Therapeutic Uses of Electricity, Delivered at Guy's Hospital. PMID- 28997008 TI - Briquet on the Mode of Action and Administration of the Salts of Quinine. PMID- 28997007 TI - Report on Cholera in the Gujrat District. PMID- 28997009 TI - Dr. Fayrer on Cobra Poison. PMID- 28997011 TI - The Concurrence of Epidemics. PMID- 28997010 TI - Fragmentary Remarks on New and Old Medicine. PMID- 28997013 TI - Case of Multiple Calculus Vesicae. PMID- 28997012 TI - Notes on the Causation of Periodic Fever. PMID- 28997014 TI - Cases of Dysmenorrhoea, Treated with Olutkombol (Abroma Agustum). PMID- 28997015 TI - Sunstroke. PMID- 28997016 TI - Quinine as an Emmenagogue. PMID- 28997017 TI - Report on Preventive Measures Adopted at Dinapore to Mitigate an Epidemic of Cholera. PMID- 28997018 TI - Compound Dislocation of Wrist; Primary Union under Antiseptics; Death by Tetanus on the Tenth Day; Post-Mortem Examination of the Injury. PMID- 28997019 TI - The Education of "Dhais". PMID- 28997020 TI - A Case of Cerebral Rheumatism. PMID- 28997021 TI - A Remarkable Medico-Legal Case. PMID- 28997023 TI - Tetanus and Its Treatment. PMID- 28997022 TI - Olutkombul. PMID- 28997024 TI - The Indian Medical Service. PMID- 28997025 TI - Large Doses of Chloral Hydrate. PMID- 28997027 TI - Sewage Irrigation. PMID- 28997026 TI - Cholera. PMID- 28997028 TI - The Fund for Widows and Orphans of Medical Officers. PMID- 28997030 TI - Case of Infantile Convulsions. PMID- 28997029 TI - Phlebitis Umbilicalis. PMID- 28997031 TI - M. Ricord on the Treatment of Syphilis. PMID- 28997033 TI - Hyperpyrexia Treated by Cold and Quinine. PMID- 28997032 TI - A Rare Case of Nasal Calculus. PMID- 28997034 TI - Quinine as an Emenagogue. PMID- 28997035 TI - On the Fall of Temperature Accompanying Great Wounds by Fire-Arms. PMID- 28997036 TI - Affections of the Eye Following Dengue. PMID- 28997037 TI - Bullet Wound of Right Lung in a Child Three and a Half Years Old. PMID- 28997039 TI - Hypodermic Injection of Ergotin in Inter-Haemorrhages. PMID- 28997038 TI - Medical News. PMID- 28997041 TI - Scarlatina in India. PMID- 28997040 TI - Recent Sanitary Legislation in England. PMID- 28997042 TI - Report on the Epidemic of Dengue in the Dacca District during 1872. PMID- 28997043 TI - Sewage Irrigation. PMID- 28997044 TI - A Case of Cystic Tumour; Operation. PMID- 28997046 TI - Microscopical Researches into the Agents Producing Cholera. PMID- 28997045 TI - Vernacular Medical Education. PMID- 28997047 TI - A Case of Large Fatty Tumour. PMID- 28997048 TI - Cholera in Calcutta during the Year 1872. PMID- 28997049 TI - Haemorrhage from a Ruptured Aneurism of the Femoral Artery at Poupart's Ligament; Ligature of Both the External Iliac and Femoral Arteries by Carbolized Catgut; Recovery. PMID- 28997050 TI - M. Oulmont on Hyoscyamine. PMID- 28997052 TI - Alligator Bite. PMID- 28997051 TI - Native Medical and Surgical Practice in Marwar. PMID- 28997053 TI - Columbidae. PMID- 28997054 TI - A Case of Cholera Treated by Injection of Salines and Transfusion of Blood. PMID- 28997056 TI - The Beauperthuy Treatment of Leprosy. PMID- 28997055 TI - Lithotomy. PMID- 28997057 TI - Translation. PMID- 28997058 TI - Lock Hospital Administration in 1871. PMID- 28997059 TI - The Aboo Lawrence School. PMID- 28997060 TI - Report on Cholera in the Hoshungabad District during 1871-1872. PMID- 28997061 TI - A New Vesical Irrigator. PMID- 28997062 TI - On Some Prominent Fallacies in Epidemiology. PMID- 28997063 TI - Amputation in the Scapulo-Humeral Articulation. PMID- 28997064 TI - A Typical Case of Typhus Fever. PMID- 28997066 TI - Remarks on Dr. Lyons' "Treatise on Relapsing or Famine Fever." PMID- 28997065 TI - Indigenous Drugs. PMID- 28997067 TI - Case of Malformation of the Lower Half of the Body. PMID- 28997068 TI - Malarial Fever. PMID- 28997069 TI - Dr. Mouat on Health Administration in India. PMID- 28997070 TI - Cholera. PMID- 28997071 TI - A Case of Lithotomy with Very Rapid Recovery. PMID- 28997073 TI - The Contagious Diseases' Act in England. PMID- 28997072 TI - Cases and Observations. PMID- 28997074 TI - The New Warrant for the Army (British Medical Department). PMID- 28997075 TI - On Some Affections of the Skin Occurring in Pregnant and Puerperal Women. PMID- 28997076 TI - Rough Notes on the Common Forms of Skin Disease Met with in Calcutta. PMID- 28997078 TI - M. Gilette on Gun-Shot Wounds. PMID- 28997077 TI - Calcutta Milk. PMID- 28997080 TI - Small-Pox. PMID- 28997079 TI - Medical News. PMID- 28997082 TI - Medical Missions in Bengal. PMID- 28997081 TI - Intravenous Injection of Ammonia in Snake-Bite. PMID- 28997083 TI - The Solvent Action of the Papaya Juice on the Nitrogenous Articles of Food. PMID- 28997084 TI - On the Etiology and Hygiene of Cholera. Part II. PMID- 28997085 TI - The Treatment of Inveterate Ague. PMID- 28997086 TI - Amputation at the Shoulder-Joint for Rapidly Spreading Traumatic Gangrene. PMID- 28997087 TI - A Rare Case of Urethral Calculus. PMID- 28997088 TI - The Operation for the Removal of Scrotal Tumours (Elephantiasis Scroti). PMID- 28997090 TI - Filaria Sanguinis Hominis. PMID- 28997089 TI - Microscopical Researches into the Agents Producing Cholera. PMID- 28997091 TI - The Medical Service of the French Army. PMID- 28997092 TI - Cases from Practice. PMID- 28997093 TI - Experiments on Cobra Poison and on a Reputed Antidote. PMID- 28997094 TI - A Medico-Legal Case: Death of a Girl from the Effects of Rupture of the Vagina. PMID- 28997095 TI - Report on the Epidemic of Dengue in the Dacca District during 1872. PMID- 28997097 TI - Rupture of the Bladder. PMID- 28997096 TI - A Complicated Case of Scrotal Hernia. PMID- 28997099 TI - Eighteen Hundred and Seventy-Two. PMID- 28997100 TI - Cholera. PMID- 28997098 TI - Effusion into the Pericardium in Strangulation. PMID- 28997101 TI - On Rupture of the Perinaeum. PMID- 28997102 TI - Case of Elephantiasis of the Prepuce, Weighing 22lbs; Excision; Recovery. PMID- 28997104 TI - Medical News. PMID- 28997103 TI - Columbidae. PMID- 28997105 TI - State Encouragement of Inoculation in Bengal! PMID- 28997106 TI - Typhoid Fever in the Native Army. PMID- 28997107 TI - Chloride of Ammonium in the Treatment of Hepatic Disease in India. PMID- 28997109 TI - Impure Water and Cholera in India. PMID- 28997108 TI - Case of Snake-Bite. PMID- 28997111 TI - Cholera. PMID- 28997110 TI - Notes on Sanitation. PMID- 28997112 TI - Cases from Practice. PMID- 28997113 TI - The Sun's Rays as a Cause of Disease. PMID- 28997115 TI - The Death-Rate among European Troops in India. PMID- 28997114 TI - Cholera at Puri. PMID- 28997116 TI - Rough Notes on the Common Forms of Skin Disease Met with in Calcutta. PMID- 28997118 TI - Cholera among Assam Coolies. PMID- 28997117 TI - Fragmentary Remarks on New and Old Medicine. PMID- 28997119 TI - A Rare Case of Wound of the Abdominal Wall and Colon. PMID- 28997120 TI - Dr. Fayrer's Treatment of Snake-Bite by Artificial Respiration. PMID- 28997121 TI - Sunstroke. PMID- 28997123 TI - Cases of Death by Hanging. PMID- 28997122 TI - Abortion, Iliac Abscess, Death from Cardiac Embolism. PMID- 28997124 TI - A Case of Cholera Treated by Hypodermic Injection of Nitrite of Amyl. PMID- 28997125 TI - Medical News. PMID- 28997126 TI - Report on the Water Supplied from the Calcutta Hydrants during the Year 1872. PMID- 28997127 TI - Goitre and Cretinism in the Bari Dooab, Gurdaspur. PMID- 28997128 TI - Case of Extravasation of Urine Caused by Calculus, Lateral Lithotomy, and Recovery. PMID- 28997129 TI - Observations on the Nature of Cholera Poison. PMID- 28997131 TI - Report on the Causes of Reduced Mortality in the French Army Serving in Algeria. PMID- 28997130 TI - Hydrocele of the Tunica Vaginalis Connected through the Inguinal Canal, with a Large Cyst Situated within the Abdomen; Cured by Repeated Injections of Iodine. PMID- 28997133 TI - The Burdwan Fever. PMID- 28997132 TI - Mortuary Registration in the District of Gurdaspur, Punjab. PMID- 28997135 TI - Extracts from the Records of Bengal Medical Department. PMID- 28997134 TI - Dengue in the Calcutta La Martiniere. PMID- 28997136 TI - Afloat or Ashore. PMID- 28997137 TI - The Annual Meeting of the Bengal Branch of the British Medical Association. PMID- 28997139 TI - Extracts. PMID- 28997138 TI - Clinical Notes of Cases Recently Treated in the General Hospital, Calcutta. PMID- 28997140 TI - Guinea-Worm Treated by the Local Application of Carbolic Acid. PMID- 28997142 TI - Vaccination in the Punjab. PMID- 28997141 TI - Abscess of the Spleen. PMID- 28997143 TI - Notes on the Journey Home. PMID- 28997144 TI - Death Caused by Swallowing Native Tooth-Stick. PMID- 28997145 TI - On Lunar Influence over Malarious Fevers. PMID- 28997146 TI - Report on the Means Adopted to Stamp out Small-Pox at Umballa, 1869. PMID- 28997147 TI - New Work on Anatomy in Oordoo. PMID- 28997149 TI - Remarks on Cyst-Infected Meat at Meean Meer; Its Nature and Prevention. PMID- 28997148 TI - Professor Syme's Recent Illness. PMID- 28997151 TI - Education in Natural and Physical Science. PMID- 28997150 TI - Cystic Tumour of the Left Labium. PMID- 28997152 TI - Selections from Ophthalmic Practice. PMID- 28997154 TI - Passage of a Calculus from the Female Bladder. PMID- 28997153 TI - On Puncture of the Knee-Joint in the Treatment of Synovitis. PMID- 28997155 TI - Remittent and Continued Fevers. PMID- 28997156 TI - The Quid Pro Quo. PMID- 28997157 TI - The Jails and Jail System of India. PMID- 28997158 TI - The Furlough Rules of 1868. PMID- 28997159 TI - The Peking Hospital. PMID- 28997160 TI - The North Suburban Hospital. PMID- 28997161 TI - On the Bite of the Sea-Snake. PMID- 28997162 TI - A Successful Case of Venomous Snake-Bite. PMID- 28997164 TI - Extracts. PMID- 28997163 TI - Arm Presentation. Version Five Hours after Rupture of the Membranes. PMID- 28997166 TI - The Camp at Umballa. PMID- 28997165 TI - Note on Embelia Ribes as a Remedy for Tape-Worm. PMID- 28997167 TI - The East Indian Railway. PMID- 28997168 TI - A Case of Extensive Injuries of the Hands, and a Successful Case of Rhinoplastic Operation. PMID- 28997169 TI - Progress of the Medical and Collateral Sciences. PMID- 28997170 TI - Local Correspondence. PMID- 28997171 TI - Hill Stations in Bengal. PMID- 28997172 TI - Extracts from the Records of the Bengal Medical Department. PMID- 28997173 TI - Selections from Ophthalmic Practice. PMID- 28997174 TI - Heart Disease in India. PMID- 28997175 TI - The Indian Medical Gazette. PMID- 28997176 TI - Delenda Est Carthago? PMID- 28997177 TI - Case of Criminal Abortion, by a Native Medicine. PMID- 28997178 TI - Experiments on the Influence of Snake-Poison. PMID- 28997179 TI - Cholera. PMID- 28997180 TI - The Carbolic Acid Treatment of Wounds. PMID- 28997182 TI - Experiments on the Action of Snake-Poison and Its Antidote: Conducted at the Gwalior Residency. PMID- 28997181 TI - Sub-Assistant Surgeons. PMID- 28997183 TI - Melanopathia. PMID- 28997184 TI - Progress of the Medical and Collateral Sciences. PMID- 28997185 TI - Indigenous Drugs. PMID- 28997186 TI - English Correspondence. PMID- 28997187 TI - Prevailing Diseases in the Angami Naga Hills. PMID- 28997188 TI - Subordinate Medical Education in India. PMID- 28997189 TI - Summary of Fifty Post-Mortem Examinations of Inhabitants of the Jessore District, Performed in the Jail Hospital. PMID- 28997190 TI - Sanitary Commissioners. PMID- 28997191 TI - Joseph Fayrer Decorated. PMID- 28997192 TI - Cholera. PMID- 28997193 TI - English Correspondence. PMID- 28997194 TI - Proceedings of the Bengal Branch of the British Medical Association. PMID- 28997195 TI - Hysteria. PMID- 28997196 TI - Summary of Fifty Post-Mortem Examinations Performed in the Jessore Jail Hospital. PMID- 28997197 TI - Subordinate Medical Education. PMID- 28997198 TI - Dispensaries in H. H. the Nizam's Dominions. PMID- 28997199 TI - Railway Surgeons in India. PMID- 28997200 TI - Sun-Stroke. PMID- 28997201 TI - The Jails and Jail System of India. PMID- 28997202 TI - Rattle His Bones over the Stones. PMID- 28997203 TI - Two Cases of Poisoning by Daturah Stramonium. PMID- 28997204 TI - The New Nomenclature of Diseases. PMID- 28997205 TI - Cholera Enquiry. PMID- 28997206 TI - Progress of the Medical and Collateral Sciences. PMID- 28997207 TI - Cui Bono? PMID- 28997209 TI - Lock Hospitals. PMID- 28997208 TI - Sub-Assistant Surgeons. PMID- 28997210 TI - Subordinate Medical Education in India. PMID- 28997211 TI - Of Snake-Poison and Its Antidotes. PMID- 28997212 TI - The Governor-General's Surgeon. PMID- 28997213 TI - Intestinal Haemorrhage. PMID- 28997215 TI - Circumstances Attending the Death of the Late Mr. R. Thorp, at Sirinagar. PMID- 28997214 TI - The Viceroy's Private Surgeon. PMID- 28997216 TI - Cholera. PMID- 28997217 TI - Progress of the Medical and Collateral Sciences. PMID- 28997218 TI - Experiments on the Influence of Certain Reputed Antidotes for Snake-Poisoning. PMID- 28997219 TI - The Jails and Jail System of India. PMID- 28997220 TI - On Certain Doubtful Points in the Pathology of Cholera. PMID- 28997222 TI - On the Nasal Administration of Sulphate of Quinine. PMID- 28997221 TI - Note on Sulphurous Acid. PMID- 28997223 TI - Septennial Examinations of Sub-Assistant Surgeons. PMID- 28997224 TI - Extracts. PMID- 28997225 TI - Cases of Amputation at the Hip-Joint. PMID- 28997226 TI - On the Removal of Deeply and Firmly Impaired Foreign Bodies. PMID- 28997227 TI - Ventilation in India. PMID- 28997229 TI - Medical Education at Dispensaries. PMID- 28997228 TI - Hepatic Abscess. PMID- 28997230 TI - Experiments on the Action of Snake-Poison When Applied to the Surface of the Conjunctiva, and Also on the Influence of Eau De Luce in the Treatment of Snake Poisoning. PMID- 28997231 TI - The Physiological Action of Quinine. PMID- 28997232 TI - Memorandum on the Effects of Famine in Rajpootana. PMID- 28997233 TI - Contributions from the Mitford Hospital, Dacca. PMID- 28997234 TI - Notes on Fourteen Cases of Cholera Treated by Hypodermic Injection of Strychnine. PMID- 28997235 TI - Experiments on the Influence of Snake-Poison on the Blood of Animals. PMID- 28997236 TI - Note on Cholera. PMID- 28997237 TI - Case of Smothering. PMID- 28997238 TI - Abdominal Aneurism Bursting into the Left Pleural Cavity. PMID- 28997240 TI - The Jail and Jail System of India. PMID- 28997239 TI - Primary Amputation of Thigh; Rapid Recovery under Antiseptic Treatment. PMID- 28997242 TI - French Medical Service. PMID- 28997241 TI - On the Use of Stellar Incisions in Certain Operations Followed by a Circular Cicatrix. PMID- 28997243 TI - Immunity of a Monkey to Strychnine. PMID- 28997244 TI - Small-Pox and Vaccination in Bhurtpoor. PMID- 28997245 TI - Cessation of Small-Pox in Ireland. PMID- 28997246 TI - Case of Suffocation. PMID- 28997247 TI - The East Indian Railway. PMID- 28997249 TI - Regarding Some Ordinary Applications Used in Surgery. PMID- 28997248 TI - Compound Fracture of the Leg; Death from Disturbed Innervation Inducing Jaundice and Ischuria. PMID- 28997250 TI - Education of Native Doctors. PMID- 28997251 TI - Results of Sanitation in India. PMID- 28997252 TI - Extract from an Ispection Report on Hooghly, by Deputy Inspector-General of Hospitals G. Saunders. PMID- 28997254 TI - Experiments on the Influence of Snake-Poison, and the Use of Certain Reputed Antidotes; and the Effects of Excision, &c. PMID- 28997253 TI - Case of Hydrocephaloid Disease. PMID- 28997255 TI - Contagious Diseases' Acts. PMID- 28997257 TI - Extract from a Report on the Sanitary State of the City of Umritsir by Assistant Surgeon A. Taylor, Civil Surgeon. PMID- 28997256 TI - Notes on Three Cases of Cholera Treated by Hypodermic Injection of Liquor Ammoniae. PMID- 28997259 TI - The Sanitary Commission of Bengal. PMID- 28997258 TI - A Case of Worms, Distoma Hepaticum, or Liver Fluke, in the Human Intestines. PMID- 28997260 TI - Cholera. PMID- 28997261 TI - Stricture of the Urethra; Death from Urethral Fever and Uraemia. PMID- 28997263 TI - Extracts. PMID- 28997262 TI - Pulsating Abdominal Tumour. PMID- 28997265 TI - Abscess of Spleen with Empyema. PMID- 28997264 TI - Dr. Cornish on Opium and Ipecacuanha in Dysentery. PMID- 28997266 TI - Strangulated Inguinal Hernia, as It Is Met with among Natives; Its Treatment by Full Doses of Opium. PMID- 28997267 TI - Experiments on the Accumulation of Foul Air in Ill-Ventilated Rooms. PMID- 28997268 TI - On the Relation between the Variolous Disease of Cattle Called "Gootee," and True Vaccinia, with Special Reference to Inoculation and Vaccination. PMID- 28997269 TI - Extracts from the Records of the Bengal Medical Department. PMID- 28997270 TI - Medical Missionaries in India. PMID- 28997271 TI - Feigned Tumor of the Jaw. PMID- 28997272 TI - Paucity of Medical Officers. PMID- 28997273 TI - Cases from Practice. PMID- 28997274 TI - Local Correspondence. PMID- 28997275 TI - The Jails and Jail System of India. PMID- 28997277 TI - Cuilibet in Arte Sua Perito Est Credendum. PMID- 28997276 TI - Native Hospital at Howrah. PMID- 28997278 TI - Subordinate Medical Education. PMID- 28997279 TI - General Paralysis of the Insane. PMID- 28997280 TI - Sanitation (Communicated). PMID- 28997281 TI - Native Medical Progress in India. PMID- 28997283 TI - Native Mortality. PMID- 28997282 TI - A Disputed Case of Obstinate Costiveness. PMID- 28997284 TI - Indian Experiences of Lithotrity. PMID- 28997285 TI - Retention of Urine; Paracentesis Vesicae. PMID- 28997286 TI - Local Correspondence. PMID- 28997287 TI - Native Doctors' English! PMID- 28997288 TI - Cholera. PMID- 28997289 TI - Punctured Wound of the Leg, &c. PMID- 28997291 TI - Summary of Post-Mortem Examinations. PMID- 28997290 TI - Hydatid Disease of the Liver. PMID- 28997292 TI - Native Beneficence. PMID- 28997293 TI - Local Correspondence. PMID- 28997294 TI - Note on Dry Earth Dressing. PMID- 28997296 TI - The Influence of Cold in Preventing the Anoesthetic Effect of Chloroform. PMID- 28997295 TI - Cantharides in Cholera. PMID- 28997298 TI - Extracts from the Records of the Bengal Medical Department. PMID- 28997297 TI - Antiseptic Treatment of Necrosis. PMID- 28997300 TI - A Case of Rupture of the Heart. PMID- 28997299 TI - Temperature of the Body in Health and Disease. PMID- 28997301 TI - Heat Apoplexy. PMID- 28997302 TI - Scientific Information. PMID- 28997303 TI - Experiments on the Influence of Snake Poison, and on the Injection of Liquor Ammoniae into the Venous Circulation as an Antidote. PMID- 28997304 TI - Post Partum Haemorrage; Death from Shock. PMID- 28997305 TI - Note on the Antiseptic Treatment of Wounds. PMID- 28997306 TI - On Lunar Influence over Malarious Fevers. PMID- 28997307 TI - The New Nomenclature of Diseases. PMID- 28997308 TI - Apoplexy. PMID- 28997309 TI - Summary of Fifty Post-Mortem Examinations of Inhabitants of the Jessore District, Performed in the Jail Hospital. PMID- 28997310 TI - Cases from Ophthalmic Practice: Herpes Zoster Frontalis. PMID- 28997311 TI - Cases of Heat Apoplexy. PMID- 28997312 TI - Results of Sanitation in India. PMID- 28997313 TI - On the Influence of Snake-Poison When Applied to Unwounded Surfaces. PMID- 28997314 TI - Retention of Urine; Discharge of Pus with Urine; Rapid Development and Subsidence of an Abdominal Tumour. PMID- 28997315 TI - Experiments on the Influence of Snake-Poison, and on the Effects of Certain Methods of Treatment. PMID- 28997316 TI - On the Relations between the Variolous Disease of Cattle Called "Gootee" and True Vaccinia, with Special Reference to Inoculation and Vaccination. PMID- 28997317 TI - Cholera. PMID- 28997319 TI - Extracts. PMID- 28997318 TI - The Delhi Ulcers. PMID- 28997321 TI - Dr. Cornish on Opium and Ipecacuanha in Dysentery. PMID- 28997320 TI - The Experiments on Snake-Poison. PMID- 28997322 TI - Antagonistic Action of Opium to Belladona. PMID- 28997323 TI - Irish Correspondence. PMID- 28997324 TI - The Want of Surgical Mechanicians in India. PMID- 28997325 TI - The Furlough Rules and the Medical Service. PMID- 28997326 TI - A Case of Aphasia. PMID- 28997327 TI - Abscess in the Cavity of the Tunica Vaginalis, &c. PMID- 28997328 TI - Health of the Central Provinces. PMID- 28997329 TI - Professor Petenkoffer's Theory of Cholera. PMID- 28997330 TI - Case of Sympathetic Orchitis. PMID- 28997331 TI - Dr. John Murray on Cholera. PMID- 28997332 TI - Experiments on the Influence of Snake-Poison and on the Injection of Certain Fluids into the Venous Circulation as Antidotes, and on the Application of the Ligature and Actual Cautery. PMID- 28997333 TI - Case of Dislocation of the Patella, Inwards. PMID- 28997334 TI - Herpes Frontalis. PMID- 28997335 TI - Case of Profuse Hoemorrhage of Which the Cause Was Uncertain. PMID- 28997336 TI - Preventive Sanitation in the Bhawulpore State. PMID- 28997337 TI - Abstract of a Case of Enteric Fever. PMID- 28997338 TI - Professor Syme. PMID- 28997339 TI - Amputation of Leg for Caries; Recovery under the Care of Dr. Baillie. PMID- 28997340 TI - Hypodermic Injection of Liquor Ammoniae in Cholera. PMID- 28997341 TI - Deaths from Snake-Bites: A Trial, Condensed from the Sessions Report. PMID- 28997342 TI - A Case of Shoulder-Presentation; Spontaneous Expulsion. PMID- 28997343 TI - Oxaluria, and a Case of Albuminaria: Extracted from Annual Regimental Report. PMID- 28997345 TI - Extracts. PMID- 28997344 TI - Local Correspondence. PMID- 28997346 TI - The Drainage and Conservancy of Calcutta. PMID- 28997347 TI - Report on the Jails, &c., of Eastern Bengal. PMID- 28997348 TI - Severe Injury to the Wrist-Joints; Recovery. PMID- 28997349 TI - English Training for Native Doctors. PMID- 28997350 TI - Calcutta Native Hospital.-Excision of the Elbow; Recovery under the Care of Dr. Baillie. PMID- 28997351 TI - Captain Jennings' Punkah-Pulling Machine. PMID- 28997352 TI - Report on Typhoid Fever in the 92nd Gordon Highlanders. PMID- 28997353 TI - Carbolic Acid in Small-Pox. PMID- 28997354 TI - The Medical Service and the New Furlough Rules. PMID- 28997355 TI - Irish Correspondence. PMID- 28997356 TI - Lahore Medical School. PMID- 28997357 TI - Ice in Chloroform Accidents. PMID- 28997359 TI - Drinking Water in Bengal. PMID- 28997358 TI - Extracts. PMID- 28997361 TI - Chronic Arsinical Poisoning-Complete Recovery. PMID- 28997360 TI - On the Use of Petroleum or Earth-Oil as an Antiseptic in the Treatment of Surgical Diseases. PMID- 28997362 TI - At What Point Is It Best to Open the Knee-Joint for the Removal of Pus? PMID- 28997363 TI - Experiments on the Influence of Snake-Poison of the Cobra, the Daboia, and the Bungarus, and of Certain Methods of Treatment. PMID- 28997364 TI - What Is Contre-Coup? PMID- 28997366 TI - Subsoil Water. PMID- 28997365 TI - Historical Evidence Regarding the Practice of Using Large Doses of Opium and Ipecacuanha in the Treatment of Acute Tropical Dysentry. PMID- 28997367 TI - Division of Sphincter Ani in Rectal Abscess. PMID- 28997368 TI - Jamaica Medical News. PMID- 28997369 TI - Experiments on the Use of the Ligature and Carbolic Acid in the Treatment of Snake-Bites. PMID- 28997370 TI - Tatties at Night. PMID- 28997371 TI - Case of Insidious Dysentery. PMID- 28997372 TI - Hypodermic Injection of Morphia in the Vomiting of Pregnancy. PMID- 28997374 TI - Correspondence. PMID- 28997373 TI - Case of Slight Injury of the Head Followed by Blood-Poisoning, and Death from Cardiac Apnoea in an English Child Aged 41/2 Years. PMID- 28997376 TI - On Maladies Attributed to Lunar Influence -Rheumatism, Paralysis, Ocular, &c. PMID- 28997375 TI - Extracts from the Records of the Bengal Medical Department. PMID- 28997377 TI - Boils. PMID- 28997379 TI - Correspondence. PMID- 28997378 TI - Belladona an Antidote to Opium. PMID- 28997381 TI - Primary Cancer of the Liver; Secondary Deposit in the Intestines and Pleurae. PMID- 28997380 TI - A Hard Case. PMID- 28997382 TI - Fees for Inquests. PMID- 28997383 TI - The Nagpore Medical School. PMID- 28997384 TI - Three Cases of Typhoid Fever. PMID- 28997385 TI - Extension of Knowledge in Rajpootana. PMID- 28997386 TI - Enucleation of Suppurating or Diseased Glands in the Groin. PMID- 28997388 TI - Native Midwives. PMID- 28997387 TI - Burnt Alum in Fungus Testis. PMID- 28997389 TI - Case of Locomotor Ataxy. PMID- 28997391 TI - Cholera Hospitals. PMID- 28997390 TI - Fibrous Tumour of the Upper Jaw Removal. PMID- 28997392 TI - Three Cases of Ictus Fulmenis Which Occurred during the Late Hazara Campaign. PMID- 28997393 TI - On Sub-Soil Drainage, by Mr. Clark, C.E. PMID- 28997394 TI - Local Correspondence. PMID- 28997395 TI - Case of Lodgment of Foreign Body in the Bladder; Extraction by Perinael Incision Recovery. PMID- 28997396 TI - The Jails and Jail System of India. PMID- 28997397 TI - Aneurism in the Army. PMID- 28997398 TI - The Royal Sanitary Commission. PMID- 28997399 TI - Notes from a Surgeon-Major on Furlough. PMID- 28997400 TI - Medical Missionaries in India. PMID- 28997401 TI - Death from Swallowing a Miswak or Tooth-Stick. PMID- 28997403 TI - Indigenous Food. PMID- 28997402 TI - Case of Cutaneous Anaesthesia. PMID- 28997404 TI - Extracts. PMID- 28997405 TI - Treatment for Heat Apoplexy. PMID- 28997407 TI - Extracts. PMID- 28997406 TI - Case of Chionyphe Carterii. PMID- 28997409 TI - The Future of the Indian Medical Service. PMID- 28997408 TI - A Case of Sudden Death from Rupture of the Spleen. PMID- 28997410 TI - Is Quinine an Abortifacient? PMID- 28997412 TI - Cases Treated by Surgeon-Major F. Odevine, F.R.C.S. (Hydatid Tumour of the Spleen). PMID- 28997411 TI - Dermoid Tumour on Cornea and Sclerotic. PMID- 28997414 TI - 1877. PMID- 28997413 TI - Report on an Outbreak of Cholera in the 8th Regiment, B. N. I., Stationed at Agra. PMID- 28997416 TI - Medical News. PMID- 28997415 TI - Case of Stricture of the OEsophagus. PMID- 28997417 TI - Report on a Case of Death from Severe Internal Injuries in Which a Diseased Spleen Escaped Rupture. PMID- 28997418 TI - After-Results in Lithotomy Cases. PMID- 28997419 TI - Case of Excision of the Elbow-Joint. PMID- 28997420 TI - Malarial Paralysis and Apoplexy. PMID- 28997421 TI - The "Plague" of Kumaun and Garhwal. PMID- 28997422 TI - Notes of a Case of Cataract: Loss of Greater Part of Vitreous Humour during the Operation: Ultimate Satisfactory Results. PMID- 28997423 TI - Case of Strangulated Inguinal Hernia, with Gangrene of the Gut: Recovery, with Artificial Anus. PMID- 28997424 TI - Case of Excision of the Knee-Joint. PMID- 28997425 TI - Medical News. PMID- 28997426 TI - Murder or Suicide. PMID- 28997427 TI - Mosquitoes and Haematozoa. PMID- 28997428 TI - Vital Statistics of the Native Army of Bengal for the Year 1876. PMID- 28997429 TI - Do You Believe in Presentiment. PMID- 28997430 TI - Tension. PMID- 28997431 TI - Aspiration and Aspersion. PMID- 28997432 TI - Medico-Topographical Notes on Subathoo. PMID- 28997433 TI - Lecture on Rickets. PMID- 28997434 TI - Cases from Practice. PMID- 28997435 TI - A Century of Medical Education in the United States. PMID- 28997436 TI - The Interior Economy of Army Hospitals in India. PMID- 28997437 TI - Ten Cases of Synovitis of the Knee-Joint, Treated by Aspiration and Rest. PMID- 28997438 TI - Cinchona Febrifuge. PMID- 28997439 TI - Case of Typhoid Fever in a Hindoo. PMID- 28997440 TI - On the Extraction of the Lens in Its Capsule. PMID- 28997441 TI - Medical News. PMID- 28997443 TI - Suicide in China. PMID- 28997442 TI - The Calcutta Medical College. PMID- 28997444 TI - Operative Surgery in the Azamgarh Sudder Dispensary. PMID- 28997445 TI - Medical Reorganization. PMID- 28997446 TI - Gleanings from a Mofussil Practice. PMID- 28997447 TI - Case of Stone in the Female Bladder. PMID- 28997448 TI - Vital Statistics of the Presidency Jail, Calcutta, during the Years 1871-1876. PMID- 28997449 TI - Compound Fracture of the Cranium, Accompanied by Symptoms of Compression Trephining-Death. PMID- 28997450 TI - A Case of Thrombosis Resulting in Death. PMID- 28997451 TI - Case of Double Hydronephrosis with Pyelitis Calculosus of the Left Kidney. PMID- 28997452 TI - Extraction of a Bullet after Being Thirty-Seven Years in the Leg of a Man. PMID- 28997453 TI - Medical Heroism. PMID- 28997454 TI - Case of Strangulated Inguinal Hernia Successfully Treated by Inversion: Under Care of Mr. J. W. Higginson. PMID- 28997456 TI - Does Imprisonment in India Involve Increased Risk to Life? PMID- 28997455 TI - Cataract. PMID- 28997457 TI - Suicide in India. PMID- 28997459 TI - The Causation of Cataract. PMID- 28997458 TI - Bromide of Potassium in Writer's Palsy. PMID- 28997460 TI - Cartilaginous Degeneration of the Capsule of the Spleen. PMID- 28997461 TI - Case of Acute Rheumatism Rapidly Cured by Salicylic Acid. PMID- 28997462 TI - Suggestions for the Treatment of Cholera. PMID- 28997463 TI - Report on an Outbreak of Stomatitis in the 31st Regiment Native Infantry. PMID- 28997465 TI - Carbolic Acid as an External Application in Small-Pox. PMID- 28997464 TI - Carbolic Acid in Whooping Cough. PMID- 28997466 TI - Salicin, Salicylic Acid and the Salicylates. PMID- 28997467 TI - Cases of Tracheotomy. PMID- 28997468 TI - Nerve Stretching in Anaesthetic Leprosy. PMID- 28997470 TI - Medical News. PMID- 28997469 TI - Dacca Mitford Hospital. PMID- 28997472 TI - Case of Excision of Knee-Joint; Recovery. PMID- 28997473 TI - Sanitation in Bengal. PMID- 28997471 TI - Report of an Outbreak of Cholera in Detachments of the 41st Regiment Native Infantry and 7th Bengal Cavalry, Morar. PMID- 28997474 TI - Case of Disseminated Choroiditis. PMID- 28997476 TI - A Case of Fatal Thermal Fever. PMID- 28997475 TI - Kashmir. PMID- 28997478 TI - Cases Reported by Surgeon R. D. Murray, M.B. B.M.S. PMID- 28997477 TI - A Unique Accident While Swimming. PMID- 28997479 TI - Intestinal Haemorrhage in Cholera. PMID- 28997480 TI - The Interior Economy of Army Hospitals in India. PMID- 28997481 TI - Do You Believe in Presentiment? PMID- 28997482 TI - Presentiment. PMID- 28997483 TI - A Case of Faecal Fistula of 51/2 Years' Standing Cured by Operation and Continued Pressure. PMID- 28997484 TI - Separation of the Fronto-Parietal Suture. PMID- 28997485 TI - Hospitalism and Some of the Methods by Which Septicaemia May Be Prevented. PMID- 28997486 TI - Clinical Observations in Ophthalmic Surgery. Cases of Cataract Previously Operated on by Native Sathiyas. PMID- 28997487 TI - Medical News. PMID- 28997488 TI - Mixed Anaesthesia. PMID- 28997490 TI - Poisoning in Bombay. PMID- 28997489 TI - A Case of Compound Comminuted Fracture of the Left Humerus: Excision: Recovery. PMID- 28997491 TI - The Subordinate Medical Department. PMID- 28997492 TI - Cholera in Relation to Certain Physical Phenomena. PMID- 28997493 TI - Diagnosis of Diseases of the Eye Made Easy. PMID- 28997494 TI - Syphilitic Dactylitis. PMID- 28997496 TI - The Sanitation of Simla. PMID- 28997495 TI - On the Operative Proceedings for Artificial Pupil. PMID- 28997497 TI - Health of Calcutta during the First Quarter of 1878. PMID- 28997498 TI - Lecture on the Detection of Particles of Hepatic Structure in Abscess of the Liver. PMID- 28997499 TI - Remarkable Injury of the Heart. PMID- 28997501 TI - Fever and Drainage. PMID- 28997500 TI - Post-Mortem Reports on Some Cases of Cerebral, Cerebro-Spinal, and Spinal Disease or Injury. PMID- 28997503 TI - The Fevers of British Burma. PMID- 28997502 TI - Penetrating Wound of the Abdomen, with Intestinal Protrusion. PMID- 28997504 TI - Ourselves. PMID- 28997505 TI - Notes on the Interior Economy of Army Hospitals in India. PMID- 28997506 TI - Report on an Outbreak of Cholera in Gorakhpur Jail, 1877. PMID- 28997508 TI - Enteric Fever in Burma. PMID- 28997507 TI - Cases Treated by Assistant-Surgeon Poornoo Chunder Ghose. PMID- 28997509 TI - Clinical Lecture on Sclerosis of Bone. PMID- 28997511 TI - Medical Honors. PMID- 28997510 TI - Case of Popliteal Aneurism Cured by Digital Compression. PMID- 28997512 TI - Is Quinine an Abortifacient? PMID- 28997513 TI - Medical News. PMID- 28997515 TI - The Recent Appointment to the Eye Infirmary. PMID- 28997514 TI - A Novel Method of Restoring Sensibility. PMID- 28997516 TI - Too Many Cooks. PMID- 28997517 TI - Goa Powder as a Remedy in Psoriasis. PMID- 28997518 TI - Quinine as an Abortifacient. PMID- 28997519 TI - Health of Calcutta during the Last Quarter of 1876. PMID- 28997520 TI - Post-Mortem Reports on Some Cases of Cerebral, Cerebro-Spinal, and Spinal Disease or Injury. PMID- 28997521 TI - Cases of Lithotomy. PMID- 28997522 TI - The Function of the Mosquito. PMID- 28997523 TI - Medico-Topographical Notes on Subathoo. PMID- 28997525 TI - Hospitalism and Some of the Methods by Which Septicaemia May Be Prevented. PMID- 28997524 TI - Case of Cancerous Ulceration of the Throat, Simulating Syphilis. PMID- 28997526 TI - Treatment and Statistical Details of the Treatment of 600 Cases of Malarious Fever in the Bhopal Battalion Hospital by Cinchona Febrifuge or Mixed Alkaloids. PMID- 28997527 TI - Statistical Geography. PMID- 28997528 TI - Report of the Sanitary Commissioner with the Government of India for 1876. PMID- 28997529 TI - Cases of Removal of Scrotal Elephantiasis. PMID- 28997530 TI - Treatment of Liver Abscess by Aspiration. PMID- 28997531 TI - Vital Statistics of the European Army in India in 1876. PMID- 28997532 TI - The Use of Bael in Bowel Complaints. PMID- 28997533 TI - Medical News. PMID- 28997534 TI - Medical Administration in Bengal. PMID- 28997535 TI - Purpura Hoemorrhagica; Dry Gangrene of Both Feet in a Child: Death. PMID- 28997537 TI - Lunatic Asylums in Victoria. PMID- 28997536 TI - Case of Atresia of the Hymen,-Haemometra. PMID- 28997538 TI - Medical News. PMID- 28997539 TI - Divination Amongst the Khasias, and the Punishment of Witchcraft. PMID- 28997540 TI - Injury to a Knee Antiseptically Treated. PMID- 28997542 TI - Cases of Fever and Acute OEdema Treated at the Mayo Hospital. PMID- 28997541 TI - Kashmir. PMID- 28997544 TI - Report of the Chemical Examiner, Bengal, for the Year 1877-78. PMID- 28997543 TI - A New Remedy for Dysentery. PMID- 28997545 TI - The Dose of Salicylate of Soda Illustrated by Two Cases. PMID- 28997547 TI - Notes from Hospital Practice. PMID- 28997546 TI - A Death Caused by Mistaking Prostatic Enlargement for Stricture. PMID- 28997548 TI - Another Suggestion for the Treatment of Cholera. PMID- 28997550 TI - Surgeon-General Gordon on Enteric Fever in the European Army of Madras. PMID- 28997549 TI - Remarks on a Case of Amputation of the Penis. PMID- 28997551 TI - Local Therapeutics. PMID- 28997553 TI - Remarks on a Case of Chyluria Treated with Creasote. PMID- 28997552 TI - Nerve-Stretching in Anaesthetic Leprosy. PMID- 28997554 TI - Case of Trephining for Abscess of the Brain. PMID- 28997556 TI - Remarks on Eleven Cases of Lithotomy Performed by the Left Lateral Method. PMID- 28997555 TI - Impetigo Folliculorum. PMID- 28997557 TI - Liver Abscess Treated by Aspiration. PMID- 28997559 TI - The Social Position of the Profession of Medicine. PMID- 28997558 TI - Clinical Notes in Ophthalmic Surgery; 146 Cases of Cataract. PMID- 28997561 TI - Martin Memorial. PMID- 28997560 TI - Gleanings from a Mofussil Practice. PMID- 28997562 TI - Case of Acute Pneumonia: Recovery under Veratrum. PMID- 28997563 TI - The Famine Commission. PMID- 28997564 TI - Radical Cure of a Case of Direct Inguinal Hernia. PMID- 28997565 TI - Case of Intusussception in an Adult: Laparotomy and Enterotomy; Death Seven Hours after Operation. PMID- 28997568 TI - Extract. PMID- 28997567 TI - Famine Statistics. PMID- 28997566 TI - Notes of a Case of Fracture of the Skull. PMID- 28997569 TI - Homoeopathy in the University of Calcutta. PMID- 28997570 TI - Medical News. PMID- 28997571 TI - Vesical Calculus: Lithotomy. PMID- 28997573 TI - Cholera, a Malarious Disease. PMID- 28997572 TI - A Word on the Treatment of Scorpion Sting. PMID- 28997575 TI - Milk Treatment of Chyluria. PMID- 28997574 TI - Vital Statistics of the Presidency Jail, Calcutta, during the Years 1871-1876. PMID- 28997576 TI - Change of Air, with Special Reference to Mooltan. PMID- 28997578 TI - The Abu Lawrence Asylum. PMID- 28997577 TI - The Madras Medical College. PMID- 28997580 TI - Sarcomatous Tumour of Left Upper Jaw: Partial Excision of Bone. PMID- 28997579 TI - The Famine Commission. PMID- 28997581 TI - A Case of Hypertrophy of Both Eyelids; Deficiency of Cranium over Torcular Herophili; Tumours over Both Eyebrows and Right Side of Face and over Trunk and Extremities. PMID- 28997582 TI - Atrophy of the Optic Papillae. PMID- 28997583 TI - The Hot Weather Morning Walk of the European Soldier: Communicated. PMID- 28997584 TI - Is It True? PMID- 28997585 TI - Notes on the Interior Economy of Army Hospitals in India: Chapter III. PMID- 28997587 TI - The Health of Bengal Jails in 1877. PMID- 28997586 TI - Radical Cure of Hernia (Wood's Operation). PMID- 28997588 TI - The Parkes Memorial Fund. PMID- 28997589 TI - Kashmir. PMID- 28997590 TI - Case of Peripheral Paralysis of the Third Nerve. PMID- 28997591 TI - On Syphilitic Contraction of Muscles. PMID- 28997592 TI - Professor Balfour of Edinburgh. PMID- 28997593 TI - Hemp (Ganja) Smoking in Tetanus on a New Principle. PMID- 28997594 TI - Turpentine. PMID- 28997595 TI - A Case of Fatal Thermal Fever(?). PMID- 28997596 TI - Health of the Jails of the N. W. Provinces and Oudh in 1877. PMID- 28997598 TI - Therapeutical Laws. PMID- 28997597 TI - The Health of Calcutta during the 2nd Quarter of 1878. PMID- 28997599 TI - Medical News. PMID- 28997601 TI - Quarantine. PMID- 28997600 TI - Extract. PMID- 28997602 TI - Radical Cure of Hernia (Wood's Operation.). PMID- 28997603 TI - Barhang. PMID- 28997604 TI - Post Mortem Notes on Cases of Enteric Fever Which Occurred during the Late Epidemic at Bareilly. PMID- 28997605 TI - Local Therapeutics. PMID- 28997606 TI - Attendance on Soldiers by Civil Practitioners. PMID- 28997607 TI - Diet in Indian Military Hospitals. PMID- 28997608 TI - Lightning Accident. PMID- 28997610 TI - The Epidemic Phase of Cholera in India. PMID- 28997609 TI - Report of the Mayo Hospital, Lahore, for the Year 1877. PMID- 28997611 TI - A Functional (?) Derangement of the Circulatory System Observed in European Soldiers in the Hot Weather. PMID- 28997612 TI - On the Condition of the Heart in Cholera Collapse. PMID- 28997613 TI - The Fungus Disease of India. PMID- 28997614 TI - Cases Reported by Surgeon-Major F. Odevaine. PMID- 28997615 TI - Notes on Enteric Fever. PMID- 28997616 TI - Manufacture of Morphia at Ghazeepore. PMID- 28997617 TI - Cholera in 1874. PMID- 28997618 TI - A Hospital for the Blind and Incurable. PMID- 28997619 TI - The Army Hospital Corps. PMID- 28997620 TI - The Rational Treatment of Cholera; with Chemical and Pathological Remarks. PMID- 28997621 TI - Cases Treated by Surgeon-Major T. E. B. Brown. PMID- 28997622 TI - On the Phytodermata or Parasitic Diseases of the Skin (Tineae) of Vegetable Origin. PMID- 28997623 TI - Notes of a Case of Elephantiasis Arabum. PMID- 28997624 TI - Case of Sting. PMID- 28997625 TI - The Gurjon Oil Treatment of Leprosy. PMID- 28997626 TI - Report on the Medico-Legal Returns, Received from the Civil Surgeons in the Bengal Presidency during the Years 1870, 1871, and 1872. PMID- 28997627 TI - Medical News. PMID- 28997628 TI - Report on a Case of Cholera in the Bhopal Battalion. PMID- 28997629 TI - Cases. PMID- 28997631 TI - 1875. PMID- 28997630 TI - Medical News. PMID- 28997632 TI - Report on the Medico-Legal Returns, Received from the Civil Surgeons in the Bengal Presidency during the Years 1870, 1871, and 1872. PMID- 28997633 TI - The Burdwan Fever. PMID- 28997634 TI - Life. PMID- 28997635 TI - Simple Oblique Fracture of Left Femur Just above the Condyles, and Subsequent Extensive Suppurative Disorganisation of the Corresponding Knee-Joint: Amputation (Secoodary) of the Thigh at Its Upper Third: Recovery. PMID- 28997636 TI - Acupuncture in Chronic Muscular Rheumatism. PMID- 28997637 TI - On the Phytodermata or Parasitic Diseases of the Skin (Tineae) of Vegetable Origin. PMID- 28997638 TI - On the Practice of Hakims in the North-Western Provinces. PMID- 28997640 TI - A Case of Haemic Murmur of the Heart. PMID- 28997639 TI - Cases Illustrating Different Types or Degrees of Severity of Cholera at Different Periods. PMID- 28997641 TI - Life. PMID- 28997643 TI - Abstract of a Report on the Epidemic of Cholera in the Jail at Laufen on the Salzach. PMID- 28997642 TI - The Soil in Its Relations to Disease. PMID- 28997645 TI - Snake-Poisoning in Australia. PMID- 28997644 TI - Rapid Recovery after Operation for Strangulated Hernia. PMID- 28997646 TI - Report on the Medico-Legal Returns, Received from the Civil Surgeons in the Bengal Presidency during the Years 1870, 1871, and 1872. PMID- 28997647 TI - Medical News. PMID- 28997648 TI - The Plague. PMID- 28997649 TI - A Case of Chylous Urine. PMID- 28997650 TI - Case of Strangulated Umbilical Hernia Reduced by Inversion. PMID- 28997651 TI - The Burdwan Fever. PMID- 28997652 TI - Cases of Anasarca Treated with Skimmed Milk. PMID- 28997653 TI - Lead in Aerated Waters. PMID- 28997655 TI - International Medical Congress, Philadelphia. PMID- 28997654 TI - On the Phytodermata or Parasitic Diseases of the Skin (Tineae) of Vegetable Origin. PMID- 28997656 TI - Report on the Outbreak of Cholera at Nowgong, Bundlecund, in July 1875. PMID- 28997657 TI - Dr. Fayrer. PMID- 28997658 TI - Harvey and Vivisection. PMID- 28997659 TI - The Memorial to the Late Dr. Parkes. PMID- 28997660 TI - Abdominal Abscess; Communication with Gall Bladder, Extraction of Three Biliary Calculi: Recovery. PMID- 28997661 TI - On the Treatment of Malignant Cholera, by Nitrite of Amyl and Hydrate of Chloral. Illustrated by a Case. PMID- 28997662 TI - Clinical Remarks Addressed to the Students Attending the Surgical Dispensary, Medical College Hospital. PMID- 28997663 TI - Appendices to the Report on the Medico-Legal Returns Received from the Civil Surgeons in the Bengal Presidency during the Years 1870, 1871, and 1872. PMID- 28997664 TI - Quarantine at Roorkee in 1872. PMID- 28997665 TI - The Use of Drainage Tubes. PMID- 28997666 TI - Treatment of Scorpion Stings. PMID- 28997668 TI - Hepatic Abscess Which Burst into the Bowels: Death. PMID- 28997667 TI - Cases of Eye Operation. PMID- 28997669 TI - Gurjon-Oil Treatment of Leprosy. Reply to Surgeon G. C. Roy, M.D., F.R.S. PMID- 28997671 TI - Water-Supply to the Shipping. PMID- 28997670 TI - General Martine. PMID- 28997673 TI - Extract. PMID- 28997672 TI - Observations on "Tinning" Cooking Pots in India. PMID- 28997674 TI - Case of Tetanus Treated by Hydrate of Chloral and Quinine: Recovery. PMID- 28997675 TI - Sulphate of Copper Lotion in Prickly Heat. PMID- 28997676 TI - Case from Practice-Calculi Vesicae. PMID- 28997677 TI - Inquiry into the Changes Which Iron Compounds Undergo before Absorption into the Blood. PMID- 28997679 TI - Night Blindness. PMID- 28997678 TI - Case of Enteric Fever. PMID- 28997680 TI - Sanitation in Calcutta. PMID- 28997681 TI - Sanitation in Calcutta. PMID- 28997682 TI - Sulphurous Acid as an Antiseptic in the Treatment of Wounds and Injuries. PMID- 28997683 TI - Congenital Hernia of the Lung. PMID- 28997684 TI - Functional Disorders of the Liver. PMID- 28997685 TI - Case of Synovial Effusions Complicating Hemiplegia. PMID- 28997687 TI - Progress in Therapeutics. PMID- 28997686 TI - Case of Snake-Bite; Treatment by Cold Douche, Forced Exercise, Subcutaneous Injection of Liquor Ammonia, and Galvanism: Recovery. PMID- 28997688 TI - Notes on Infantile Diseases in India. PMID- 28997690 TI - Effects of Alcohol in the Human Economy. PMID- 28997689 TI - Syme's Amputation at the Ankle-Joint. PMID- 28997691 TI - Recent Rulings under the New Army Medical Warrant. PMID- 28997692 TI - Report on the Medico-Legal Returns, Received from the Civil Surgeons in the Bengal Presidency during the Years 1870, 1871, and 1872. PMID- 28997693 TI - Sanitation in Calcutta. PMID- 28997695 TI - Medical News. PMID- 28997694 TI - Lead as an Application to Wounds; Its Antiphlogistic and Antiseptic Properties. PMID- 28997696 TI - Warburg's Tincture. PMID- 28997697 TI - Report on a Case in Which a Foreign Body Was Embedded in the Foot for 13 Months without Exciting Inflammation. PMID- 28997698 TI - Remarks on "Cut Throat," Illustrated by a Case. PMID- 28997699 TI - A Case of Syphiloma of the Heart, Lungs, and Liver. PMID- 28997700 TI - Syphilis; and the Recent Discussion at the Pathological Society of London. PMID- 28997701 TI - Report on the Snake-Bite Cases Which Occurred in Bengal, Behar, Orissa, Assam, Cachar, &c., during the Year 1873-74. PMID- 28997702 TI - Case of Partial Paralysis, Supposed to Have Followed the Injudicious Administration of Arsenic. PMID- 28997703 TI - Hakims Are Not so Ignorant as Doctors Believe Them to Be. PMID- 28997704 TI - A Hill Sanitarium for Burmah. PMID- 28997705 TI - Medical News. PMID- 28997706 TI - Report on the Medico-Legal Returns, Received from the Civil Surgeons in the Bengal Presidency during the Years 1870, 1871, and 1872. PMID- 28997707 TI - A Case of Cataract in a Leper; Extraction of Lens: Recovery in Seven Days. PMID- 28997708 TI - A Case of Leprosy Healed by Gurjon Oil and Afterwards by Oil of Turpentine and Mustard. PMID- 28997709 TI - The Marriage of near Kin. PMID- 28997710 TI - On the Phytodermata or Parasitic Diseases of the Skin (Tineae) of Vegetable Origin. PMID- 28997711 TI - On the Theory and Treatment of the Collapse Stage of Cholera, Ague and Irritant Poisons. PMID- 28997712 TI - The Cholera Outbreak in Goa Bagan. PMID- 28997713 TI - Cases of Strangulated Inguinal Hernia Treated during the Year 1875. PMID- 28997714 TI - Movements of Maxima. PMID- 28997715 TI - Case of Excision of Upper Half of Patella after Transverse Fracture of Long Standing. Under Care of W D. Stewart, Offg. Civil Surgeon. PMID- 28997716 TI - Quarantine at Roorkee in 1872. PMID- 28997717 TI - Extracts. PMID- 28997718 TI - Hypodermic Injection of Hydrate of Chloral in Cases of Malignant Cholera. PMID- 28997719 TI - Turmeric Flower as a Remedy for Gonorrhoea. PMID- 28997720 TI - A Want. PMID- 28997721 TI - Diagnosis Wanted. PMID- 28997722 TI - Hypodermic Injection of Chloral Hydrate in Tetanus. PMID- 28997723 TI - Arterial Haemorrhage. Was It Known to the Ancients? PMID- 28997724 TI - Quinine in Hooping Cough. PMID- 28997725 TI - Notes on Infantile Diseases of India. PMID- 28997726 TI - Case of "Recent" Strangulated Inguinal Hernia; Minor Operation: Recovery, with Some Remarks on Chloroform in India. PMID- 28997727 TI - Quarantine at Roorkee in 1872. PMID- 28997728 TI - Syphilis and the Recent Discussion at the Pathological Society of London. PMID- 28997729 TI - Stricture at External Meatus, with Phimosis, Followed by Abscess and Fistula; Remarks. PMID- 28997730 TI - The Subordinate Medical Department in Army Hospitals. PMID- 28997731 TI - Case of Pneumonia of Right Lung. PMID- 28997732 TI - Poisoning by Tartar Emetic. PMID- 28997734 TI - Medical News. PMID- 28997733 TI - Pseudo-Hypertrophic Paralysis (Duchenne.). PMID- 28997735 TI - The Gurjon Oil Treatment of Leprosy, at Port Blair. PMID- 28997736 TI - Case of Remittent Fever Simulating Enteric Fever. Under the Care of Dr. Lucas. PMID- 28997737 TI - The Competition for the Medical Services. PMID- 28997738 TI - Experiments with Cobra Poison. PMID- 28997739 TI - Cases of Dysentery Simulating Cholera. PMID- 28997740 TI - A Fatal Case of Snake-Bite; Intravenous Injection of Ammonia. Remarks on the Application of the Ligature in Snake-Bite. PMID- 28997741 TI - Case of Coma Followed by a State of Consciousness to within 12 Hours of Death. P. M.-Large Cerebral Abscess Found. PMID- 28997742 TI - Muscat. PMID- 28997743 TI - Extracts. PMID- 28997744 TI - On the Use of the Rectum in Operations for Lithotomy. PMID- 28997746 TI - Medical News. PMID- 28997745 TI - The Bather's Earache. PMID- 28997747 TI - The Snake-Stone. PMID- 28997748 TI - Notes on Infantile Diseases of India. PMID- 28997749 TI - The Non-Emetic Use of Ipecacuanha. PMID- 28997750 TI - The Pathology of Suicide. PMID- 28997751 TI - Ascarides Proving Suddenly Fatal by Perforative Peritonitis. PMID- 28997752 TI - Night Blindness. PMID- 28997753 TI - Salivation from Local Application of the Biniodide of Mercury. PMID- 28997755 TI - Treatment of Scorpion Stings. PMID- 28997754 TI - Hypodermic Injection of Quinine in Fever. PMID- 28997756 TI - Cases Reported by F. Odevaine, Surgeon-Major. PMID- 28997757 TI - Infants' Food. PMID- 28997759 TI - Medical News. PMID- 28997758 TI - A Popular Fallacy, or a Physiological Fact; Which Is It? PMID- 28997760 TI - Conservative Surgery. PMID- 28997762 TI - Malarious Fever in Midnapore in 1874-75. PMID- 28997761 TI - Skin and Other Diseases of Indian and Hot Climates Generally. PMID- 28997764 TI - District Skeleton Maps for Civil Surgeons. PMID- 28997763 TI - Fibrous Tumour between the Epiglottis and Base of the Tongue Removed with the Ecraseur. PMID- 28997765 TI - Report on the Medico-Legal Returns, Received from the Civil Surgeons in the Bengal Presidency during the Years 1870, 1871, and 1872. PMID- 28997766 TI - Sudden Transfers of Army Medical Officers in May. PMID- 28997767 TI - Emphysematous Condition of the Right Auricular Appendix in Cases of Death by Hanging. PMID- 28997768 TI - The Aboo Lawrence School. PMID- 28997769 TI - Malarious Fevers and Rainfall in Rajpootana. PMID- 28997770 TI - Plague Spots in Calcutta. PMID- 28997771 TI - Remarks on Venesection. PMID- 28997772 TI - Chronic Alcoholism. Death by Rupture of the Liver from a Fall. PMID- 28997773 TI - Sudden Death from Latent Aneurism. PMID- 28997774 TI - Medical News. PMID- 28997775 TI - Remarks on a Case of Hepatic Abscess; Evacuation by Dieulafoy's Pneumatic Aspirator. PMID- 28997776 TI - Extracts. PMID- 28997777 TI - Early Dentition. PMID- 28997778 TI - Case of Fnugus Foot. PMID- 28997779 TI - Case of Gangrene of Left-Arm and Fore-Arm, Following Fracture of Humerus and Tight Bandaging. Amputation. Recovery. PMID- 28997780 TI - Notes on Enteric Fever. PMID- 28997781 TI - Erratum: Poisoning by Tartar Emetic. AB - [This corrects the article on p. 272 in vol. 11.]. PMID- 28997782 TI - On the Treatment of Fractures by Position. PMID- 28997783 TI - Are All 'Suicides' Insane? PMID- 28997784 TI - On Hair Grafting. PMID- 28997785 TI - Rupture of the Pericardium. PMID- 28997786 TI - Nitrite of Amyl in Ague, &C. PMID- 28997788 TI - The Ashanti Campaign of 1873. PMID- 28997787 TI - Case of Lithotomy; Removal of Two Calculi Weighing Respectively, 5oz. 4dr. 52gr., and 7dr. 8gr. Total 61/2oz.,-Recovery. PMID- 28997790 TI - Subscribers to the Parkes-Memorial Fund. PMID- 28997789 TI - Calcutta Health Officer's Report for Quarter Ending 30th September, 1876. PMID- 28997791 TI - On the Rational Treatment of Cholera, and Remarks on the Outbreak at Ranchee. PMID- 28997792 TI - Examination for Promotion in the Indian Medical Service. PMID- 28997793 TI - Two Recent Medico-Legal Cases in the Medical College Hospital. PMID- 28997794 TI - Impure Aerated Waters in Calcutta and Bombay. PMID- 28997796 TI - A Case of Posioning by Carbolic Acid. PMID- 28997795 TI - Notes of a Case of Paraplegia, Treated in the Wards of the Second Resident Surgeon, Presidency General Hospital. PMID- 28997797 TI - Medical News. PMID- 28997798 TI - The New Army Medical Warrant. PMID- 28997800 TI - Ourselves, and the Profession in India. PMID- 28997799 TI - A Popular Fallacy; Or, a Physiological Fact: Which Is It? PMID- 28997801 TI - "Intermittent Haemorrhage" from Malarial Influence. PMID- 28997802 TI - On the Phytodermata or Parasitic Diseases of the Skin (Tineae) of Vegetable Origin. PMID- 28997803 TI - Warburg's Tincture. PMID- 28997804 TI - Emphysematous Condition of the Right Auricular Appendix in a Case of Death by Hanging. PMID- 28997805 TI - Remarks on the Gurjun Oil Treatment of Leprosy at Port Blair. PMID- 28997806 TI - Report on the Medico-Legal Returns, Received from the Civil Surgeons in the Bengal Presidency during the Years 1870, 1871, and 1872. PMID- 28997807 TI - Indian Soda-Water and Aerated-Water. PMID- 28997809 TI - Norman Chevers, M. D. PMID- 28997808 TI - Notes of Three Cases of Scarlatina Treated in the Wards of the Second Resident Surgeon, Presidency General Hospital. PMID- 28997810 TI - Injection of Quinine in Gonorrhoea. PMID- 28997811 TI - Injection of Cinchona Infusion in Gonorrhoea. PMID- 28997812 TI - Brow-Ague, or Brow-Ache. Dyspepsia versus Malaria. PMID- 28997813 TI - The Army Medical Warrant. PMID- 28997814 TI - Review of Burdwan Fever. PMID- 28997816 TI - Notes on Infantile Disease in India. PMID- 28997815 TI - Injection of Quinine in Gonorrhoea. PMID- 28997817 TI - Oxyuris Vermicularis, an Unmentioned Cause of Fistula-In-Ano. PMID- 28997818 TI - The Practice of Hakims in the North-Western Provinces. PMID- 28997819 TI - Value of Gukhru in Certain Forms of Seminal Discharges and Incontinance of Urine. PMID- 28997820 TI - Skin and Other Diseases of Indian and Hot Climates Generally. PMID- 28997821 TI - Treatment of Scorpion Sting. PMID- 28997822 TI - Case of Enteric Fever, Showing the Value of Turpentine in the Treatment of This Disease. PMID- 28997823 TI - Two Cases Showing the Peculiar Effects of Chloroform in Different Individuals. PMID- 28997825 TI - Medical News. PMID- 28997824 TI - Report on the Medico-Legal Returns, Received from the Civil Surgeons in the Bengal Presidency during the Years 1870, 1871, and 1872. PMID- 28997826 TI - Dispensaries and Sickness in the Province of Bengal, during 1874. PMID- 28997827 TI - Two Cases of Paralysis on the Side of the Brain Lesion under the Care of Surgeon J. F. P. McConnell, M. B. PMID- 28997828 TI - Sanitary Notes in Poona. PMID- 28997829 TI - Remarks on the Pathology and Treatment of Lichen Tropicus or Prickly Heat. PMID- 28997830 TI - Treatment of "Prolapsed Funis". PMID- 28997831 TI - A Case of Internal Obstruction of the Large Intestine. PMID- 28997833 TI - Calcutta Tanks. PMID- 28997832 TI - Salicin, Salicylic Acid and Its Salts. PMID- 28997834 TI - Report on an Outbreak of Cholera in the Secundra Jail, Agra, during June and July 1878. PMID- 28997835 TI - Goalundo Dispensary.-Compound Fracture of the Cranium, Accompanied by Symptoms of Compression-Trephining-Recovery. PMID- 28997836 TI - Short Sketch of Two Cases of Cholera. PMID- 28997837 TI - Azamgarh Dispensary.-1.-Large Enchondroma of Submaxillary Gland: Removal: Complete Excision of Gland Necessitated; 2.-Large Enchondroma of Parotid Gland: Removal: Excision of Greater Part of Gland. PMID- 28997838 TI - The Same. PMID- 28997839 TI - Case of Nervous Aphonia. PMID- 28997840 TI - Palas Papra. PMID- 28997841 TI - A Case of Compound Comminuted Fracture of the Femur. PMID- 28997842 TI - Cataract. PMID- 28997844 TI - Bengal Lunatic Asylums. PMID- 28997843 TI - A Case of Cholera Treated by Hypodermic Injections of Choloral Hydrate. PMID- 28997845 TI - Medical News. PMID- 28997846 TI - Barhang Query Bartang. PMID- 28997847 TI - Local Therapeutics. PMID- 28997848 TI - Fever and Irrigation. PMID- 28997849 TI - A Case of Croup : Tracheotomy; Death. PMID- 28997850 TI - Brief Report of Some Cases Treated in the Soory Charitable Dispensary. PMID- 28997851 TI - Current Medical Topics. PMID- 28997852 TI - Child-Mortality by Dr. Pfeiffer of Weimar. PMID- 28997853 TI - A Very Remarkable and Extraordinary Condition of the Renal Organs : Single Kidney. PMID- 28997854 TI - The Calcutta Medical Society. PMID- 28997855 TI - Contributions to Forensic Medicine. PMID- 28997856 TI - Cases from the Khundwa Dispensary Case Book. PMID- 28997857 TI - Poisoning by Red Arsenic. PMID- 28997859 TI - Medical News. PMID- 28997858 TI - Notes of Post-Mortem Examination of Two Cases of Judicial Hanging. PMID- 28997860 TI - The Opium Question. PMID- 28997861 TI - Hypodermic Injection of Chloral Hydrate in Cholera. PMID- 28997862 TI - A Case of Enlargement of the Female Breast Treated in the Soory Charitable Dispensary. PMID- 28997863 TI - General Hospital, Madras. Clinical Cases from the Assistant-Physician's Wards. PMID- 28997864 TI - Medical Experiences during the Late Campaigns in Afghanistan. PMID- 28997865 TI - Current Medical Topics. PMID- 28997866 TI - Child-Mortality by Dr. Pfeiffer of Weimar. PMID- 28997867 TI - Cases of Litholapaxy. PMID- 28997868 TI - The Calcutta Medical Society. PMID- 28997869 TI - Remarks on an Anonymous Attack on His Recent Work Which Appeared Lately, in the Form of a Pseudo-Criticism, in the Columns of a Madras Newspaper. PMID- 28997870 TI - A Report on the Treatment of Ten Cases of Enteric Fever-All Ending in Recovery. PMID- 28997871 TI - Cases of Gunshot Wounds Treated in Divisional Field Hospital, Kabul. PMID- 28997872 TI - Cholera and Fever Poisons. PMID- 28997873 TI - Cases from Practice in a Bengal Village. PMID- 28997874 TI - Liebig's Wine of Phosphates. PMID- 28997875 TI - The Calcutta Medical College. PMID- 28997876 TI - Retained Menses from Imperforate Hymen-Free Incision: Recovery. PMID- 28997877 TI - Malarial Cachexy. PMID- 28997878 TI - The Subcutaneous Injection of Quinine. PMID- 28997879 TI - Cases Treated at the Huttesing Hospital, Ahmedabad. PMID- 28997880 TI - Urticaria Following the Administration of Quinine. PMID- 28997881 TI - Amaranthus Spinosa. PMID- 28997882 TI - A Case of Tiger Bite, &c., Treated in the Tavoy Hospital. PMID- 28997883 TI - Current Medical Topics. PMID- 28997884 TI - A Correction. PMID- 28997885 TI - Litholapaxy and Supra-Pubic Lithotomy. PMID- 28997886 TI - Double Quotidian Fever. PMID- 28997887 TI - The Calcutta Medical Society. PMID- 28997888 TI - Hyperpyrexia of Enteric Fever. PMID- 28997889 TI - Hot Weather Expeditions in Afghanistan. PMID- 28997890 TI - Malaria vs. Recognisable Climatic Influences. PMID- 28997891 TI - Case of Aortic Aneurism. PMID- 28997892 TI - The Calcutta Medical Society. PMID- 28997893 TI - Case from Practice in the Hospital of the 38th Regiment Bengal Infantry. PMID- 28997894 TI - Precis of Operations Performed in the Wards of the First Surgeon. Medical College Hospital, during the Year 1880. PMID- 28997895 TI - Epidemic Dropsy in Calcutta. PMID- 28997896 TI - The Mortality of Indian Jails. PMID- 28997898 TI - Current Medical Topics. PMID- 28997897 TI - Notes on Recent Therapeutics. PMID- 28997900 TI - Cases of Injury of the Knee-Joint. PMID- 28997899 TI - On the Poisonous Principle of Gloriosa Superba-Second Notice. PMID- 28997901 TI - Cholera Amongst Emigrants to the Tea Districts. PMID- 28997903 TI - Medical News. PMID- 28997902 TI - Imperforate Hymen with Retention of Menses. PMID- 28997904 TI - A Correction. PMID- 28997905 TI - Enteric and Other Fevers in Afghanistan. PMID- 28997906 TI - The Calcutta Medical Society. PMID- 28997907 TI - A Note on the Incubation Period of Guinea-Worm. PMID- 28997908 TI - Introductory Lecture on Constitutional Conditions of Surgical Importance. Delivered at the Opening of the Session, 1881-82. PMID- 28997909 TI - Reduction of an Irreducible Inguinal Hernia by the Smoking of Indian Hemp. PMID- 28997911 TI - Medical News. PMID- 28997910 TI - Cases of Ignipedites. PMID- 28997912 TI - A Case of Leprosy. PMID- 28997913 TI - The Benzoates in Dysentery. PMID- 28997914 TI - The Grievances of Civil Hospital Assistants. PMID- 28997915 TI - Cleaning Filters. PMID- 28997916 TI - Ignipedites. PMID- 28997917 TI - Special Detailed Report on a Case of Enteric Fever with Remarks on the Influence of Quinine on Temperature. PMID- 28997918 TI - Child-Mortality by Dr. Pfeiffer of Weimar. PMID- 28997919 TI - Gun-Shot Wound of the Right Arm: Amputation: Recovery. PMID- 28997921 TI - Current Medical Topics. PMID- 28997920 TI - Discharge of a Thin Watery Fluid from the Ear and Its Importance. PMID- 28997922 TI - Cinchona Cultivation in Darjeeling. PMID- 28997923 TI - Bengal Charitable Dispensaries. PMID- 28997924 TI - Lectures on Errors of Refraction and Accommodation of the Eye. PMID- 28997925 TI - Cases from Practice at a Bengal Village. PMID- 28997926 TI - The Opium Question. PMID- 28997927 TI - Child-Mortality by Dr. Pfeiffer of Weimar. PMID- 28997928 TI - A Case of Placenta Praevia Treated by Partial Separation of Placenta and Ergot: Recovery. PMID- 28997929 TI - Paralysis the Result of a Slight Fall. PMID- 28997930 TI - A Case of Imperforate Anus with Absence of Rectum. PMID- 28997931 TI - Lectures on Errors of Refraction and Accommodation of the Eye. PMID- 28997932 TI - Madras Medical College.-Valedictory Address Delivered at the Close of Season 1880 81. PMID- 28997933 TI - Suggestions on Chorea and Allied Nervous Disorders. PMID- 28997934 TI - Cases from Practice at a Bengal Village. PMID- 28997936 TI - The Calcutta Medical Society. PMID- 28997935 TI - The Causation of Enteric Fever with Remarks on Its Prevention and Treatment. PMID- 28997937 TI - A Case of Sclerosis of the Cord : Fracture of Thigh : Rapid Union and Subsequent Improvement of Symptoms. PMID- 28997938 TI - Some Cases of Abdominal Tumour. PMID- 28997939 TI - Spirillum Fever. PMID- 28997940 TI - Current Medical Topics. PMID- 28997941 TI - Current Medical Topics. PMID- 28997942 TI - Dietetic Enlargement of the Spleen, Physiological and Pathological. PMID- 28997943 TI - Cold Baths in Enteric Fever. PMID- 28997945 TI - Rotheln. PMID- 28997944 TI - A Note on the Use of Willow Leaves in Intermittent Fevers. PMID- 28997946 TI - The New Exanthem. PMID- 28997947 TI - The Prevention of Cholera. PMID- 28997948 TI - Cholera and Fever Poisons. PMID- 28997949 TI - The Ductless Glands. PMID- 28997951 TI - A Case of Abscess in the Right Anterior Lobe of the Brain with an External Communication by Means of a Sinus. PMID- 28997950 TI - Cholera and Fever Poisons. PMID- 28997953 TI - The Calcutta Medical Society. PMID- 28997952 TI - "Nim" as a Medicinal Agent in Surgery. PMID- 28997954 TI - Remarks on the Circulatien of the Brain. PMID- 28997955 TI - A Case of Irreducible Obstructed Inguinal Hernia; Symptoms of Strangulation One Month After; Operation of Herniotomy; Recovery. PMID- 28997956 TI - Report on Acute Anaemic Dropsy in Mauritius. PMID- 28997958 TI - Child-Mortality by Dr. Pfeiffer of Weimar. PMID- 28997957 TI - Medical News. PMID- 28997959 TI - Cases of Rupture of Spleen. PMID- 28997961 TI - 1880. PMID- 28997960 TI - The Afghanistan Memorial. PMID- 28997963 TI - The Jail Administration Report. PMID- 28997962 TI - A Case of Dysidrosis. PMID- 28997965 TI - Some Notes on the Different Diseases Diagnosed as Fever in the General Hospital at Madras. PMID- 28997964 TI - The Calcutta Medical Society. PMID- 28997966 TI - My Contribution towards a Clinical History of Hepatitis in India-A Personal Sketch. PMID- 28997967 TI - A Medical Sketch of Inland Emigration Operations from 1863-64 to 1879-80. PMID- 28997968 TI - Two Cases of Self-Mutilation. PMID- 28997969 TI - Case of Retained Testis. PMID- 28997971 TI - Supplement to the Indian Medical Gazette, January 1, 1881. PMID- 28997970 TI - Two Cases of Injury by Lighting. PMID- 28997972 TI - Case of Injury Requiring Double Amputation. PMID- 28997973 TI - Notes on Enteric Fever or Abdominal Typhus, with Remarks on Enteric Fever in Afghanistan and on a Case Occurring There. PMID- 28997974 TI - Case of Poisoning by Nerium Odoraum. PMID- 28997976 TI - Alcohol and Spirit Drinking Amongst Soldiers. PMID- 28997975 TI - Current Medical Topics. PMID- 28997977 TI - Extracts. PMID- 28997978 TI - Medical News. PMID- 28997979 TI - Chaulmugra (Gynocardia Odorata) in Leprosy. PMID- 28997980 TI - Sulphurous Acid Treatment of Cholera. PMID- 28997981 TI - Notes on the Interior Economy of Army Hospitals in India. PMID- 28997983 TI - A Case of Paraplegia Following Malarious Fever: Rapid Recovery under the Use of Quinine and Strychnine. PMID- 28997982 TI - Thrombosis of the Cerebellar (?) Arteries. PMID- 28997984 TI - Post-Mortem Examination of a Case of Monstrous Twins. PMID- 28997985 TI - The Cholera Epidemic in the Chittagong Division. PMID- 28997986 TI - On a New Way of Applying Mr. Lister's Method of Treating Wounds. PMID- 28997987 TI - Notes from Home. PMID- 28997988 TI - Cases (Tetanus). PMID- 28997989 TI - Dyed Quinine. PMID- 28997990 TI - Testing Tinned Cooking Pots for Lead. PMID- 28997991 TI - On Army Hospital Corps. PMID- 28997992 TI - Case of United Twins: Three Months' Old. PMID- 28997993 TI - The Insertion of Disease Intelligence in Newspapers. PMID- 28997994 TI - Notes on Pathology. PMID- 28997995 TI - Case of Cholera Treated by Sulphurous Acid: Recovery. PMID- 28997996 TI - Notes on Infantile Diseases of India. PMID- 28997997 TI - To Remove In-Growing Toe Nail. PMID- 28997998 TI - Carnification of the Lung from the Pressure of a Melanotic Cancerous Liver. PMID- 28997999 TI - Clinical Lecture on Three Cases of Rodent Ulcer, Now in the Hospital. PMID- 28998000 TI - Case of "Ainhum." PMID- 28998001 TI - A Fatal Case of Compound Depressed Fracture of the Skull, and Compound Comminuted Fracture of Radius and Ulna. PMID- 28998003 TI - Extracts. PMID- 28998002 TI - Scorpion-Sting: Death in 12 Hours. PMID- 28998004 TI - Medical News. PMID- 28998005 TI - Medico-Topographical Notes on Mean Meer. PMID- 28998006 TI - On Ulcers of the Left Leg Depending on Disease of the Spleen. PMID- 28998007 TI - Tracheotomy in a Case of Laryngitis: Recovery. PMID- 28998008 TI - Notes of Cases of Cholera Treated by Sulphurous Acid. PMID- 28998010 TI - The Aboo Lawrence School. PMID- 28998009 TI - Opium-Eating. PMID- 28998011 TI - Notes on Pathology. PMID- 28998013 TI - Nine Propositions Bearing on the AEtiology and Prophylaxis of Cholera. Deduced from the Official Reports of the Cholera-Epidemic in East India and North America. PMID- 28998012 TI - Case of Scleroderma. PMID- 28998015 TI - Typho-Malarial Fever: Is It a Special Type of Fever? PMID- 28998014 TI - Two Cases of Traumatic Tetanus: Recovery. PMID- 28998016 TI - Cases. PMID- 28998018 TI - A Report on an Outbreak of Cholera in the Old Jail Palamcottah on the 5th, 6th, and 7th of November 1876. PMID- 28998017 TI - A Case of Fracture of Skull and Other Injuries. PMID- 28998019 TI - Post-Mortem Examination in a Case of Rifleshot Injury. PMID- 28998020 TI - Notes on Pathology. PMID- 28998021 TI - Remarks on the Indian Pharmacopoeia. PMID- 28998022 TI - Notes on Infantile Diseases of India. PMID- 28998023 TI - Nerve Stretching. PMID- 28998024 TI - Cases from Practice. PMID- 28998025 TI - Observations on the Action of the Darjeeling Cinchona Febrifuge in Malarious Fevers. PMID- 28998027 TI - Medical News. PMID- 28998026 TI - Treatment of Delirium Tremens by Quinine. PMID- 28998029 TI - The Materia Medica of the Hindus. PMID- 28998028 TI - Dyed Quinine. PMID- 28998031 TI - Extracts. PMID- 28998030 TI - Case of Floating Cartaract: Extraction. PMID- 28998032 TI - Hydrophobia. PMID- 28998033 TI - Suffocation by Fumes of Charcoal. PMID- 28998034 TI - The Sulphurous Acid Treatment of Cholera. PMID- 28998035 TI - Stricture of Urethra with Perinaeal Tumour. PMID- 28998036 TI - Nine Propositions Bearing on the AEtiology and Prophylaxis of Cholera, Deduced from the Official Reports of the Cholera Epidemic in East India and North America. PMID- 28998038 TI - A Case of Traumatic Emphysema. PMID- 28998037 TI - Cases Illustrating the Effects of Fright. PMID- 28998039 TI - Results of the Treatment of Cholera by Sulphurous Acid and the Hyposulphites in the Epidemic of 1875 at Delhi. PMID- 28998040 TI - Uterine Physiology and Pathology and Their Effects on the Nervous System. PMID- 28998041 TI - Cases (Glaucoma). PMID- 28998042 TI - Surgeon-General W. G. Hunter's Report on the So-Called 'Famine Fever' of Bombay. PMID- 28998043 TI - The Treatment of Entropium and Trichiasis. PMID- 28998044 TI - Leprosy in India. PMID- 28998046 TI - Note on Cholera. PMID- 28998045 TI - Cholera Amongst Dhanger Coolies on Board the Assam Steamers. PMID- 28998047 TI - A Case of "Oriental Sore." PMID- 28998049 TI - Dr. Howard's "Direct Method" of Artificial Respiration. PMID- 28998048 TI - A Case of Acute Tonsilitis Accompanied with Suppuration of the Parotid Gland. PMID- 28998051 TI - A Case of Hydrophobia. PMID- 28998050 TI - How Far Can Ulcers of the Left Leg Be Said to Depend on Disease of the Spleen? PMID- 28998052 TI - A Clinical Lecture on Caries and Necrosis, and a New Method of Treating Them. PMID- 28998053 TI - Medical News. PMID- 28998054 TI - A Case of Guinea-Worm. PMID- 28998055 TI - Extracts. PMID- 28998056 TI - Goa Powder as a Remedy in Psoriasis. PMID- 28998057 TI - Case of Lithotomy: Stone of 20-Years' Duration: Death. PMID- 28998059 TI - The Opacitometer. PMID- 28998058 TI - Case of Excision of the Bones of the Foot. PMID- 28998060 TI - Copy of a Report on New Wines under Trial for Issue to European Hospitals in Lieu of Port. PMID- 28998061 TI - Case of Erysipeloid Inflammation of Nose, the Result of Irritation Setup by Maggots in the Posterior Nares. PMID- 28998062 TI - Pyrethrum Radix in Alopecia. PMID- 28998063 TI - Treatment of Acute Orchitis by Puncture. PMID- 28998065 TI - A Difficult Case of Lithotomy. PMID- 28998064 TI - Medical News. PMID- 28998067 TI - Extracts. PMID- 28998066 TI - Cases. PMID- 28998068 TI - Cholera in Rajpootana: With Maps Showing the Prevalence of the Disease. PMID- 28998069 TI - Antiseptic Surgery in Edinburgh. PMID- 28998070 TI - A Reply to an Address of Prof. Max Von Pettenkofer of Munich. PMID- 28998071 TI - Remarks on Enteric Fever in India, with the Details of Two Fatal Cases in Which Diarrhoea Was Absent Throughout. PMID- 28998073 TI - Dr. Marston's Appointment. PMID- 28998072 TI - Notes of Two Surgical Cases. PMID- 28998074 TI - A Novel Method of Restoring Sensibility. PMID- 28998075 TI - The Bengal Fever Commission. PMID- 28998076 TI - A Case of Iliac Abscess Opened below Poupart's Ligament with Successful Result: Death from Congestion of the Lungs. PMID- 28998077 TI - Filaria Sanguinis Hominis-Mature Form. PMID- 28998078 TI - A Case of Fracture of the Thigh, Just below the Trochanter, Treated by Flexion, with Good Results. PMID- 28998079 TI - Notes of a Case of Crocodile Bite with Removal of a Large Portion of Omentum. PMID- 28998080 TI - Short Clinical Notes and Registers of Temperature of Eighteen Doubtful or Anomalous Cases of Fever, with Remarks. PMID- 28998081 TI - A Case of (So-Called) Snake-Bite. PMID- 28998082 TI - Sanitation in Calcutta. PMID- 28998084 TI - Rum or No Rum? PMID- 28998083 TI - Case of Ovariotomy: Successful Result. PMID- 28998085 TI - A Few Practical Remarks on Enteric Fever in India. PMID- 28998087 TI - Cases. PMID- 28998086 TI - A Clinical Note on Croupous Pneumonia and Gangrene of the Lung in India. PMID- 28998088 TI - Non-Appearance of the Testes in the Scrotum in Adult Life. PMID- 28998089 TI - Sulphurous Acid Treatment of Cholera. PMID- 28998090 TI - A Reply to an Address of Prof. Max Von Petenkofer of Munich. PMID- 28998092 TI - Medical News. PMID- 28998091 TI - A Case of Traumatic Gangrene Supervening on Compound Fracture of the Left Forearm: Amputation at the Shoulder Joint: Recovery. PMID- 28998093 TI - Leukaemia and Pseudo-Leukaemia. PMID- 28998095 TI - New Army Medical Warrant. PMID- 28998094 TI - Contribution to the Practice of Midwifery (Puerperal Tetanus). PMID- 28998096 TI - Indian Medical Officers' Pensions. PMID- 28998097 TI - Extracts. PMID- 28998098 TI - Case of Compound Fracture of the Cranium with Impaction of Bone: Successfully Treated. PMID- 28998099 TI - A Case of Death from Lightning. PMID- 28998100 TI - Case of Ruptured Intestines, and Comminuted Fracture of the Second, Third, and Fourth Lumbar Vertibrae. PMID- 28998101 TI - Contribution to the Practice of Midwifery. PMID- 28998102 TI - Self-Mutilation by a Boy. PMID- 28998103 TI - Use of the Rectum in Operations for Lithotomy. PMID- 28998104 TI - To Remove Ingrowing Toe-Nail. PMID- 28998105 TI - Enteric Fever in India. PMID- 28998106 TI - Uterine Physiology and Pathology and Their Effects on the Nervous System. PMID- 28998108 TI - 1876. PMID- 28998107 TI - Cases of Amputation of Thigh, Arm, and Leg in the Mayo Native Hospital during the First Half of 1876. PMID- 28998109 TI - The Medical Consultation in the Bravo Case. PMID- 28998110 TI - On Indian Surgical Instruments; Illustrated. PMID- 28998111 TI - Medical News. PMID- 28998112 TI - Notes on Infantile Diseases of India. PMID- 28998113 TI - Extracts. PMID- 28998114 TI - Posterior Dislocation of the Knee-Joint. Rupture of False Ligaments, Excision of the Joint. PMID- 28998115 TI - Silver-Coated Pills-A Caution. PMID- 28998117 TI - Vaccination under Municipalities in Bengal, and the Revised Rules for Vaccination in the Madras Presidency. PMID- 28998116 TI - Darjeeling, Mixed Cinchona-Alkaloid. PMID- 28998118 TI - Biniodide of Mercury as a Parasiticide. PMID- 28998120 TI - Cholera Statistics. PMID- 28998119 TI - Cases. PMID- 28998121 TI - Extracts. PMID- 28998122 TI - The Cholera Epidemic of 1875. PMID- 28998123 TI - A Case of Hydrophobia. PMID- 28998125 TI - The Champion Rifle Shot of India. PMID- 28998124 TI - Cases from Practice. PMID- 28998126 TI - The Rumoured Reorganization of the Medical Departments. PMID- 28998127 TI - Two Cases of Obstruction of the Bowels and Its Results. PMID- 28998128 TI - The Snake-Stone. PMID- 28998130 TI - Report on an Outbreak of Cholera in the District, City, and Cantonments of Sailkot in August and September 1876. PMID- 28998129 TI - Contusion of the Face, with Fracture of the Nasal Bones: Tetanus: Death. PMID- 28998131 TI - Calcutta Health Officer's Quarterly Report. PMID- 28998132 TI - Hysteric Epilepsy. PMID- 28998133 TI - Medical News. PMID- 28998134 TI - A Case of Death from Lightning. PMID- 28998135 TI - Notes on Infantile Diseases of India. PMID- 28998137 TI - The Army Medical Department. PMID- 28998136 TI - A Sporadic Outbreak of Cholera. PMID- 28998138 TI - Extract. PMID- 28998139 TI - Thermal Phenomena in Injuries of the Nervous System. PMID- 28998140 TI - Medical News. PMID- 28998141 TI - Case of Arsenical Poisoning with Characteristic Appearances in the Alimentary Canal and in the Heart: Chronic Obstruction of Both Fallopian Tubes. PMID- 28998142 TI - The Sulphurous Acid Treatment of Cholera. PMID- 28998143 TI - Notes on Pathology. PMID- 28998145 TI - Nomenclature of Diseases. PMID- 28998144 TI - Acute Peritonitis Due to Contraction of the Ascending Colon: Death. PMID- 28998146 TI - The Parkes' Memorial. PMID- 28998147 TI - Malarial Cachexia in the Garo Hills. PMID- 28998148 TI - A Case of Compound Comminuted Fracture of the Right Leg: Amputation: Recovery. PMID- 28998150 TI - Cases. PMID- 28998149 TI - Nine Propositions Bearing on the AEtiology and Prophylaxis of Cholera, Deduced from the Official Reports of the Cholera Epidemic in East India and North America. PMID- 28998151 TI - Question Put at a Recent Examination of Assistant-Surgeons for Promotion. PMID- 28998153 TI - The Fellowship of the Royal College of Surgeons of England. PMID- 28998152 TI - Fever and Relief Measures in Burdwan in 1875. PMID- 28998154 TI - "Oriental Sore" or Lupus Endemicus. PMID- 28998155 TI - Hiccough of More Than Five Days' Duration, Successfully Treated by Large Doses of Quinine. PMID- 28998156 TI - Medical Registration. PMID- 28998157 TI - Extracts. PMID- 28998158 TI - Cases from Practice. PMID- 28998159 TI - Notes on Pathology. PMID- 28998160 TI - Notes on the Influence of the Seasons on Suicide. PMID- 28998161 TI - Designation of Army Medical Officers. PMID- 28998162 TI - Cases. PMID- 28998163 TI - Medical News. PMID- 28998164 TI - Notes on Infantile Diseases of India. PMID- 28998165 TI - The Competition for the Medical Services. PMID- 28998166 TI - Nine Propositions Bearing on the AEtiology and Prophylaxis of Cholera, Deduced from the Official Reports of the Cholera Epidemic in East India and North America. PMID- 28998167 TI - The Hypodermic Administration of Quinine in Intermittent Fever. PMID- 28998168 TI - Four Cases of Stone: Lithotomy: Recovery. PMID- 28998169 TI - A Case of Puerperal Tetanus Treated with Chloral Hydrate and Bromide of Potassium: Recovery. PMID- 28998170 TI - Report on Five Cases of Cholera Treated in the Medical College Hospital by Sulphur Fumigation. PMID- 28998171 TI - Murderous Assault on an European Medical Officer. PMID- 28998172 TI - Extracts. PMID- 28998173 TI - Cholera Epidemic of 1875: Quarantine and Remedial Measures. PMID- 28998174 TI - Pensions and Deferred Annuities. PMID- 28998175 TI - Fracture with Dislocation of Spine. PMID- 28998177 TI - Poor-Houses or Hospitals? PMID- 28998176 TI - History of the Cholera Outbreak in the Shahpur District in 1876. PMID- 28998178 TI - Notes on Infantile Diseases of India. PMID- 28998180 TI - Medical News. PMID- 28998179 TI - The Confectio Damocratis. PMID- 28998181 TI - Case of Idiopathic Tetanus Treated by Chloral: Recovery. PMID- 28998183 TI - Dengue. PMID- 28998182 TI - Cases. PMID- 28998184 TI - A Note on the Physiology or Mechanism of Micturition. PMID- 28998185 TI - Hypodermic Injection of Chloral Hydrate in the Collapsed Stage of Cholera: Recovery. PMID- 28998186 TI - Notes on a Case of Ring-Worm. PMID- 28998187 TI - Cases of Poisoning by "Corrosive Sublimate:" Recovery. PMID- 28998188 TI - Hydrocele of the Neck. PMID- 28998190 TI - Medical News. PMID- 28998189 TI - On the Physiology of Sugar in Relation to Blood. PMID- 28998191 TI - Case of Acute Mania, Apparently Due to Syphilis: Specific Treatment: Recovery. PMID- 28998192 TI - Therapeutic Notes on the Chloride of Calcium. PMID- 28998193 TI - Case of Poisoning from the Oleander Root (Nerium Odorum). PMID- 28998194 TI - Remarks on the Action of Snake Poison on the Blood. PMID- 28998196 TI - Extracts. PMID- 28998195 TI - Errors of Refraction; Their Diagnosis and Treatment Simply Explained. PMID- 28998198 TI - The Late Poisoning Case at Peshawar. PMID- 28998197 TI - Cases: Traumatic Gangrene of Arm: Amputation: Recovery. PMID- 28998199 TI - A Reply to an Address of Prof. Max Von Pettenkofer of Munich. PMID- 28998201 TI - Cases at Goalundo: A Case of Drowning: Death from Secondary Apnoea. Necrosis of Lower End of Tibia; Sequestrotomy: Recovery. Lacerated Wound of the Foot; Syme's Amputation at Ankle Joint: Death from Tetanus. PMID- 28998200 TI - The Late Surgeon-Major N. B. Baillie's Lithotomy Cases. PMID- 28998202 TI - Case of Emphysema of the Cellular Tissue of the Neck and Thorax in the Course of Double Pneumonia. PMID- 28998203 TI - Shakespeare on Syphilis. PMID- 28998204 TI - Asthma. PMID- 28998205 TI - The Wearing of Uniform. PMID- 28998207 TI - Curious Symptoms Following the Administration of Cinchonine. PMID- 28998206 TI - Cases from Practice: Remarkable Case of Fatty Degeneration Compound Fracture of Forearm, with Comminuted Fracture of Upper-Arm: Amputation. Case of Fracture of Skull-Trephining. PMID- 28998208 TI - The Army Medical Department. PMID- 28998209 TI - Indian Medical Officers' Pensions. PMID- 28998210 TI - Fertility of Lepers. PMID- 28998211 TI - Remarks on the Indian Pharmacopoeia. PMID- 28998212 TI - A Case of Intestinal Obstruction Successfully Treated by Aspiration at the Arrah Dispensary. PMID- 28998213 TI - Etawah Dispensary.-Case of Scalp Wound with Sloughing-The Calvarium Being Laid Perfectly Bare for about a Space of 5 Sq. Inches. PMID- 28998214 TI - Case of Traumatic Tetanus Treated with Conia. Recovery. PMID- 28998216 TI - Calcutta Medical Society. PMID- 28998215 TI - Current Medical Topics. PMID- 28998217 TI - Medical News. PMID- 28998218 TI - The Treatment of Typhoid Fever. PMID- 28998219 TI - Pettenkofer's Last Utterance on Cholera. PMID- 28998221 TI - Selections from the Records of the Indian Medical Departments. PMID- 28998220 TI - A Second Series of Ten Cases of Lithotrity at One Sitting. PMID- 28998223 TI - Epidemic among Fish. PMID- 28998222 TI - Perforation of Stomach. PMID- 28998225 TI - The Grievances of Assistant-Surgeons. PMID- 28998224 TI - Notes on the Analysis of Potable Waters. PMID- 28998227 TI - Calcutta Medical Society. PMID- 28998226 TI - Notes on the Indian Expedition to Egypt. PMID- 28998228 TI - Ophthalmic Cases: Extracts from a Medical Diary. PMID- 28998230 TI - Case of Arm Presentation and Retained Placenta. PMID- 28998229 TI - Dr. W. R. Rice on Typhus in India. PMID- 28998231 TI - On the Physiological and Medicinal Action of Hydrofluoric Acid and the Fluorides. PMID- 28998233 TI - Medical Women for India. PMID- 28998232 TI - On Enteric Fever. PMID- 28998235 TI - Current Medical Topics. PMID- 28998234 TI - Remarks on the Operation for Radical Cure of Hernia. PMID- 28998236 TI - On the Radical Cure of Hernia by Spanton's Method. PMID- 28998237 TI - A Case of Abscess of the Spleen. PMID- 28998238 TI - On Enteric Fever. PMID- 28998239 TI - Cerebral Dyspepsia. PMID- 28998240 TI - Case of Puerperal Fever with Remarks. PMID- 28998241 TI - Litholapaxy. PMID- 28998242 TI - Current Medical Topics. PMID- 28998243 TI - Cases of Penetrating Wounds of the Abdomen Caused by the Horns of Bullocks : Recovery. PMID- 28998245 TI - Notes on the Variations in the Incidence of Cholera on the Population of Towns and Villages. PMID- 28998244 TI - Notes of a Case of Dhatura Poisoning. PMID- 28998246 TI - Calcutta Medical Society. PMID- 28998247 TI - Notes on a Case of Scarlet Fever. PMID- 28998248 TI - Faecal Gas as an Illuminant. PMID- 28998249 TI - The Health of the European Army in India. PMID- 28998250 TI - Notes on Six Cases of Cholera Treated in the Hospital of the Left Wing 33rd Regiment N. I., Alipore. PMID- 28998251 TI - Case of Calculus Vesicae in a Young Girl, Removed by Crushing and Dilatation. PMID- 28998252 TI - Note on the Variations in the Incidence of Cholera on the Population of Towns and Villages. PMID- 28998253 TI - Removal of Right Side of Lower Jaw for Cystic Tumour. PMID- 28998254 TI - On the Use of Jaborandi and Pilocarpine in Fever. PMID- 28998255 TI - A Case of Tetanus : Recovery. PMID- 28998256 TI - Two Cases of Strangulated Hernia with Complications after Operation, and a Case of Wound of AEsophagus. PMID- 28998257 TI - Note on the Examination of Potable Water, with Experiments. PMID- 28998258 TI - On the Physiological and Medicinal Action of Hydrofluoric Acid and the Fluorides. PMID- 28998259 TI - Manson on the Pathology of Elephantiasis. PMID- 28998260 TI - Calcutta Medical Society. PMID- 28998261 TI - Current Medical Topics. PMID- 28998262 TI - The Treatment of Cholera. PMID- 28998263 TI - International Medical Congress. PMID- 28998265 TI - Venereal Disease in the European Army of India. PMID- 28998264 TI - On Enteric Fever. PMID- 28998266 TI - A Case of Urethral Stricture (? Malarial.). PMID- 28998267 TI - On the Treatment of Aneurism by Esmarch's Bandage. PMID- 28998268 TI - Arithmetical Pathology. PMID- 28998269 TI - Can Cholera be Generated De Novo? PMID- 28998270 TI - Cases of Laryngotomy and Tracheotomy. PMID- 28998271 TI - Calcutta Medical Society. PMID- 28998272 TI - On the Physiological and Medicinal Action of Hydrofluoric Acid and the Fluorides. PMID- 28998273 TI - Report on Some Observations in Connection with Pneumonia as Observed on the Punjab Frontier. PMID- 28998274 TI - Gunshot Fracture of Head of Humerus: Excision. PMID- 28998275 TI - On Enteric Fever. PMID- 28998276 TI - Notes of Cases of Gun-Shot Wounds. PMID- 28998277 TI - Tuberculosis. PMID- 28998278 TI - On the Preservation of Bodies for Dissection. PMID- 28998279 TI - Current Medical Topics. PMID- 28998280 TI - On a Modified Method of Using the Aspirator. PMID- 28998282 TI - Purulia Dispensary. PMID- 28998281 TI - Drs. S. Weir Mitchell and Edward T. Reichert on the Poison of Heloderma Suspectum (Cope), the Gila Monster. PMID- 28998283 TI - On Enteric Fever. PMID- 28998284 TI - Precis of Operations Performed in the Wards of the First Surgeon, Medical College Hospital, during the Year 1882. PMID- 28998285 TI - Poisoning by Green Vitriol; Recovery. PMID- 28998286 TI - Current Medical Topics. PMID- 28998288 TI - Case of Fibro-Sarcoma of Thigh. PMID- 28998287 TI - A Case of Holt's Operation for Recurrent Stricture of the Urethra. PMID- 28998289 TI - The Disposal of Sewage: No. 2. PMID- 28998290 TI - Notes on the Indian Expedition to Egypt. PMID- 28998292 TI - 1882. PMID- 28998291 TI - Notes on Indigenous Vegetable Poisons : Seeds of the Abrus Precatorius. PMID- 28998293 TI - Case of Lithotomy. PMID- 28998294 TI - Calcutta Medical Society. PMID- 28998295 TI - The Grievances of Assistant-Surgeons. PMID- 28998297 TI - Phrenology: An Address Delivered on the Occasion of the Seventh Anniversary of the Calcutta Improvement Association. PMID- 28998296 TI - Coto Bark in Dysentery. PMID- 28998298 TI - Two Unnatural Cases of Labour. PMID- 28998300 TI - Current Medical Topics. PMID- 28998299 TI - Case-Taking, with an Example. PMID- 28998301 TI - Indore Charitable Hospital-A Case of Traumatic Emphysema. PMID- 28998302 TI - On Enteric Fever. PMID- 28998304 TI - Retraction of the Flap after Syme's Amputation. PMID- 28998303 TI - Fibrinous Coagula in the Heart. PMID- 28998305 TI - On the Physiological and Medicinal Action of Hydrofluoric Acid and the Fluorides. PMID- 28998307 TI - Calcutta Medical Society. PMID- 28998306 TI - Note on a Case of Occlusion of the Orifice of the Urethra and of the Prepuce with Adhesion. PMID- 28998308 TI - In the Case of the Empress vs. Upendro Kisto Dutt. PMID- 28998309 TI - Malarial Cachexy. PMID- 28998310 TI - Case of Urethral Calculus. PMID- 28998312 TI - Experiences in Egypt. PMID- 28998311 TI - Contributions to the Practice of Midwifery. PMID- 28998313 TI - A Case of Encysted Peritoneal Effusion : Operation: Recovery. PMID- 28998314 TI - The "Black Disease" of the Garo Hills. PMID- 28998316 TI - Radical Cure of Hernia. PMID- 28998315 TI - Ophthalmic Cases. PMID- 28998317 TI - Current Medical Topics. PMID- 28998319 TI - Remarks on Fever in India. PMID- 28998318 TI - Nitrate of Silver Enema in Chronic Dysentery. PMID- 28998320 TI - Clinical Lecture on Haematocele: Delivered at the Medical College Hospital on the 25th September 1883. PMID- 28998322 TI - Radical Cure of Hydrocele by the Application of Iodoform. PMID- 28998321 TI - Correspondence. PMID- 28998323 TI - On the Physiological and Medicinal Action of Hydrofluoric Acid and the Fluorides. PMID- 28998324 TI - Some Further Notes on Colour-Blindness in India. PMID- 28998325 TI - Wound of the External Carotid and Vertebral Arteries: Ligature of the Common Carotid: Death. PMID- 28998326 TI - On the Physiological and Medicinal Action of Hydrofluoric Acid and the Fluorides. PMID- 28998327 TI - On Enteric Fever. PMID- 28998328 TI - Report on Some Observations in Connection with Pneumonia as Observed on the Punjab Frontier. PMID- 28998329 TI - Calcutta Medical Society. PMID- 28998330 TI - Etawah Dispensary. PMID- 28998331 TI - Treatment of Erysipelas with External Application of White Lead Paint. PMID- 28998333 TI - Notes on a Case of Extroversion of the Bladder. PMID- 28998332 TI - A Third Case of Judicial Hanging. PMID- 28998334 TI - A Case of Hepatic Abscess. PMID- 28998335 TI - The Drainage of Bombay. PMID- 28998336 TI - Retention of Menses from Absence of Vagina: Operation: Peritonitis: Death. PMID- 28998338 TI - Great Facts and Little Facts. PMID- 28998337 TI - Report on Surgical Operations Performed in the Mayo Hospital, Lahore, during 1882. PMID- 28998339 TI - Internal Urethrotomy. PMID- 28998341 TI - Current Medical Topics. PMID- 28998340 TI - The Nature of Snake Poisons-Viewed by the Light of the Most Recent Researches. PMID- 28998343 TI - The Same. PMID- 28998342 TI - The Feeding of Cholera Patients. PMID- 28998344 TI - A Brief Account of the Epidemic of Cholera Which Prevailed at the Station of Mettupalaiyam from 11th January 1883 to 18th March 1883. PMID- 28998345 TI - On the Physiological and Medicinal Action of Hydrofluoric Acid and the Fluorides. PMID- 28998346 TI - Chloroform and Cataract Extraction. PMID- 28998348 TI - Current Medical Topics. PMID- 28998347 TI - Precis of Operations Performed in the Wards of the First Surgeon, Medical College Hospital, during the Year 1882. PMID- 28998349 TI - Case of Penetrating Wound of the Abdomen with Laceration and Protrusion of the Spleen, Protrusion of Large Intestine and Portion of Omentum and Fracture of Two Ribs, the 9th and 10th, Terminating in Recovery. PMID- 28998350 TI - A Case of Hepatic Abscess Treated by Dr. G. C. Roy, Recovered after Free Opening and Drainage. PMID- 28998351 TI - Carbolic Acid Poisoning. PMID- 28998352 TI - Case of Obstruction of the Bowels; Recovery. PMID- 28998354 TI - Calcutta Medical Society. PMID- 28998353 TI - Hazy Cover-Glasses. PMID- 28998355 TI - The Contagious Diseases Act. PMID- 28998357 TI - The Sanitary Contrasts of the Crimean War. PMID- 28998356 TI - Two Cases of Carbuncle Treated with Nitric Acid. PMID- 28998359 TI - Mergui Charitable Dispensary. PMID- 28998358 TI - A New Disease in Calcutta (Beriberi?). PMID- 28998360 TI - Lithotomy Statistics. PMID- 28998361 TI - Mergui Charitable Despensary. PMID- 28998362 TI - Lecture on Diseases of the Hip-Joint. PMID- 28998364 TI - The Report of the Sanitary Commissioner with the Government of India for 1878. PMID- 28998363 TI - European General Hospital, Bombay.-Ovariotomy, Recovery without a Bad Symptom. PMID- 28998365 TI - Current Medical Topics. PMID- 28998366 TI - The Liver and Its Urea-Forming Function. PMID- 28998367 TI - The New Disease. PMID- 28998369 TI - Allahabad Dispensary. PMID- 28998368 TI - Clinical Lecture:-Lithotomy and Fracture of the Skull. PMID- 28998370 TI - Calcutta Medical Society. PMID- 28998371 TI - On the Association of Fracture of the Upper Third of the Ulna with Dislocation Forwards of the Head of the Radius. PMID- 28998372 TI - Bengal Notes. PMID- 28998373 TI - Partabgurh Dispensary.-Case of Herniotomy: Recovery. PMID- 28998374 TI - The Dacca Medical Society. PMID- 28998375 TI - A Case of Accidental Suffocation. PMID- 28998376 TI - Artificial Pupil in a Case of Leucoma Complicated with Partial Staphyloma of the Cornea. PMID- 28998377 TI - The Calcutta Medical Society. PMID- 28998379 TI - The Calcutta Medical Society. PMID- 28998378 TI - Srinagar Dispensary, Gurhwal. PMID- 28998381 TI - Antiseptic Surgery. PMID- 28998380 TI - A Synopsis of Recent Views Regarding the Treatment of Enteric Fever. PMID- 28998382 TI - Current Medical Topics. PMID- 28998383 TI - Medical Reorganization. PMID- 28998385 TI - Notes on Enteric Fever, or Abdominal Typhus. PMID- 28998386 TI - Topographical Report on the Town of Mandalay, Upper Burma, and Its Environs. PMID- 28998384 TI - Bengal Notes. PMID- 28998387 TI - Alleged Death from Witchcraft. PMID- 28998388 TI - Case of Hydrophobia. PMID- 28998389 TI - Official Paper. PMID- 28998390 TI - A Case of Wound of Axillary Artery: Ligature of the Vessel above and below the Seat of Injury: Death. PMID- 28998391 TI - Cuttack General Hospital:-Notes of Cases Taken by Assistant-Surgeon Chooney Lal Dass. PMID- 28998392 TI - Nerve-Stretching in Anaesthetic Leprosy. PMID- 28998394 TI - The Defamation Case. PMID- 28998393 TI - Shillong Dispensary.-Case of Ovariotomy. PMID- 28998395 TI - A Medical Sketch of Inland Emigration Operations from 1863-64 to 1879-80. PMID- 28998396 TI - Medical News. PMID- 28998397 TI - Some Observations upon the Urine in Health in India. PMID- 28998399 TI - The Calcutta Medical Society. PMID- 28998398 TI - My Contribution Towards a Clinical History of Hepatitis in India-A Personal Sketch. PMID- 28998401 TI - Current Medical Topics. PMID- 28998400 TI - Enquiry on Colour-Blindness in India. PMID- 28998403 TI - The Sale of Drugs in Calcutta. PMID- 28998402 TI - Snake-Poisoning and Its Treatment. PMID- 28998404 TI - Remarks on the Retinal Spectrum Produced by Sunlight. PMID- 28998406 TI - Current Medical Topics. PMID- 28998405 TI - Ferruginous Compounds in Sewage-Antisepsis. PMID- 28998407 TI - Gonorrhoea as Treated in Vernacular Medical Literature, Especially with Reference to Its Therapeutics. PMID- 28998409 TI - Severe Scalp-Wound: Diffuse Cellular Inflammation: Necrosis of Cranium. PMID- 28998408 TI - Some Gun-Shot Injuries. PMID- 28998410 TI - Medical Advertising. PMID- 28998411 TI - The Opium Question. PMID- 28998412 TI - Cinchona Cultivation and Alkaloid Manufacture. PMID- 28998413 TI - A Case of Ainhum. PMID- 28998414 TI - My Contribution Towards a Clinical History of Hepatitis in India-A Personal Sketch. PMID- 28998415 TI - A Medical Sketch of Inland Emigration Operations from 1863-64 to 1879-80. PMID- 28998416 TI - The Calcutta Medical Society. PMID- 28998417 TI - Medical News. PMID- 28998419 TI - Beri-Beri in Singapore. PMID- 28998420 TI - Medical News. PMID- 28998421 TI - Post-Mortem Appearances in a Case of Rape. PMID- 28998418 TI - The Treatment of Opium-Eaters. PMID- 28998422 TI - Post-Mortems and Law. PMID- 28998423 TI - Beri-Beri. PMID- 28998424 TI - Calcutta Medical Society. PMID- 28998425 TI - Cases of Mycetoma. PMID- 28998426 TI - Report on an Epidemic of Relapsing Fever in the Rupar Jail in the Years 1878-79. PMID- 28998427 TI - Notes of a Case Attacked by an Elephant: Death and Post-Mortem Appearances. PMID- 28998428 TI - Vital Resistance. PMID- 28998429 TI - Contused Wound of the Head: Intrameningeal Suppuration: Trephining: Death. PMID- 28998431 TI - The Ecbolic Action of Quinine. PMID- 28998430 TI - Pelvic Abscesses: Their Surgical Anatomy, Diagnosis and Treatment, with a Statement of Cases. PMID- 28998432 TI - The Effect of Lunar Influence on Disease. PMID- 28998434 TI - Current Medical Topics. PMID- 28998433 TI - Pay Hospitals. PMID- 28998435 TI - Personal Equipment of Medical Officers on Active Service. PMID- 28998436 TI - Abscess of Spleen Extending to and Involving the Liver. PMID- 28998437 TI - Case from Practice in the Hospital of the 38th Bengal Native Infantry. PMID- 28998438 TI - Cases Reported by Koilash Chandra Mukhopadhyay, M.B. PMID- 28998439 TI - Satkhira Charitable Dispensary.-Severe Incised Wounds; Wound of the Lung: Recovery. PMID- 28998440 TI - Charitable Dispensaries in Bengal. PMID- 28998441 TI - Excision of the Upper Jaw for Myeloid Tumour. PMID- 28998442 TI - Two Cases of General Cutaneous Papillomata. PMID- 28998444 TI - The Calcutta Medical Society. PMID- 28998443 TI - Nursing in War. PMID- 28998445 TI - Current Medical Topics. PMID- 28998446 TI - Some Notes on the Different Diseases Diagnosed as Fever in the General Hospital at Madras. PMID- 28998447 TI - A Medical Sketch of Inland Emigration Operations from 1863-64 to 1879-80. PMID- 28998449 TI - Particulars Regarding the Prevalence of Diarrhoea at Simla in 1880. PMID- 28998448 TI - My Contribution Towards a Clinical History of Hepatitis in India- A Personal Sketch. PMID- 28998451 TI - Medical News. PMID- 28998450 TI - Beri-Beri. PMID- 28998452 TI - Cholera Fever. PMID- 28998454 TI - Sulphuric Acid in Cholera. PMID- 28998455 TI - Bengal Notes. PMID- 28998453 TI - Cases Illustrating the Benefit of Belladonna in Opium-Poisoning. PMID- 28998457 TI - Ewart on Typhoid Fever. PMID- 28998456 TI - Unusual Situation of Sebaceous Cysts in the Sole of the Foot. PMID- 28998459 TI - Comparative Faecology. PMID- 28998458 TI - Current Medical Topics. PMID- 28998461 TI - The Calcutta Medical Society. PMID- 28998460 TI - Tayaya. PMID- 28998463 TI - Acute OEdema. PMID- 28998462 TI - A Case of Acute Atrophy of Liver. PMID- 28998464 TI - Medico-Topographical Report on Calcutta. PMID- 28998465 TI - Precis of Operations Performed in the Wards of the Second Surgeon, Medical College Hospital, during the Year 1879. PMID- 28998466 TI - Lecture on Diseases of the Hip-Joint. PMID- 28998467 TI - Notes on Loss of Vitreous after Cataract Extraction. PMID- 28998469 TI - Precis of Operations Performed in the Wards of the Second Surgeon, Medical College Hospital, during the Year 1879. PMID- 28998468 TI - Indian Medical Department. PMID- 28998470 TI - The Calcutta Medical Society. PMID- 28998471 TI - Pulsating Tumour of the Head. PMID- 28998472 TI - Medical Reorganization. PMID- 28998473 TI - Current Medical Topics. PMID- 28998475 TI - Medical News. PMID- 28998474 TI - Beri-Beri. PMID- 28998476 TI - Compound Depressed Fracture of Skull with Aphasia and Paralysis of the Right Upper Limbs: Recovery. PMID- 28998477 TI - Strangulated Hernia: Three Cases Successfully Treated by the Continued Application of Ice. PMID- 28998478 TI - Surgical Cases. PMID- 28998479 TI - Cases from Practice in the Hospital of the 38th Regiment, Bengal Native Infantry, at Barrackpore: Hypertrophy of the Spleen, the Result of Malarial Fever: Death from Asthenia. PMID- 28998480 TI - Cases of Affections of the Genitals in Young Children. PMID- 28998481 TI - Recovery after the Bite of a Cobra. PMID- 28998482 TI - Penetrating Abdominal Wound with Protrusion of Lacerated Intestine: Artificial Anus Temporarily Established: Ultimate Complete Recovery. PMID- 28998484 TI - Case of Elephantiasis of Scrotum. PMID- 28998483 TI - On the Poisonous Principle of Gloriosa Superba: A Chemico-Physiological Research. PMID- 28998486 TI - The Calcutta Medical Society. PMID- 28998485 TI - Case of Injury to the Antrum of Highmore. PMID- 28998487 TI - My Contribution Towards a Clinical History of Hepatitis in India-A Personal Sketch. PMID- 28998489 TI - Supplement to the Indian Medical Gazette, October 1, 1880. PMID- 28998488 TI - The Opium Question. PMID- 28998490 TI - Cobra-Bite: Immediate Treatment: Recovery. PMID- 28998491 TI - Enteric Fever in India. PMID- 28998492 TI - Decalcified Bone Drainage Tubes. PMID- 28998493 TI - Current Medical Topics. PMID- 28998494 TI - Treatment of Opium-Eaters. PMID- 28998495 TI - Case of Unnatural Labour: Both Arms Presenting: Child Extracted Piecemeal. PMID- 28998497 TI - Contribution to the Medical History of Goitre. PMID- 28998496 TI - Contribution to the Practice of Midwifery. PMID- 28998498 TI - Rape of Infant Children. PMID- 28998499 TI - Lunar Influence on Disease. PMID- 28998500 TI - On Rearing Infants. PMID- 28998502 TI - Current Medical Topics. PMID- 28998501 TI - Some Notes on the Treatment of Cholera and the Administration of Cholera Hospitals. PMID- 28998504 TI - Appendix to the Report on the Health of the Troops Forming the Vitakri Field Force. PMID- 28998503 TI - Notes on 133 Cases of Goitre Treated in the Hospital of the 38th Regiment, Bengal Native Infantry at Baxa Duar, Bhutan, from 1873 to 1875. PMID- 28998505 TI - Bengal Notes. PMID- 28998506 TI - The Calcutta Medical Society. PMID- 28998507 TI - Cases of Shark-Bite. PMID- 28998509 TI - The Calcutta Medical College. PMID- 28998508 TI - Dubbing. PMID- 28998510 TI - Memorandum on the Prevention of Sickness among Prisoners in Extra-Mural Gangs. PMID- 28998512 TI - Purulia Dispensary.-A Run of Cancer Cases. PMID- 28998511 TI - Observations on Some Interesting and Peculiar Symptoms of Cholera as Observed in Four Epidemics at Peshawar. PMID- 28998514 TI - Medical News. PMID- 28998513 TI - A Case of Excision of the Knee-Joint: And of Urethrotomy for Impacted Calculus: Recovery. PMID- 28998515 TI - Fees. PMID- 28998516 TI - Tayuya. PMID- 28998517 TI - Case of Obstruction of the Bowel. PMID- 28998518 TI - Sulphuric Acid as a Prophylactic in Cholera Outbreaks. PMID- 28998520 TI - Medical News. PMID- 28998519 TI - Warm Baths Gradually Cooled down in Increased Bodily Temperature. PMID- 28998521 TI - The Same. PMID- 28998522 TI - Cholera in the Royal Artillery in Kandahar. PMID- 28998523 TI - The Dissemination of Cholera by Human Intercourse. PMID- 28998524 TI - Notes on Early Sanitation in India. PMID- 28998525 TI - "Indigenous Drugs": (Salicylic Acid, Salicylates, and Salicin. PMID- 28998527 TI - Sulphurous Acid in Cholera. PMID- 28998526 TI - Is Quinine an Abortifacient? PMID- 28998528 TI - Cases from Practice in the Hospital of the 38th Bengal Native Infantry at Barrackpore. PMID- 28998530 TI - Medical College Hospital-Case of Abscess of the Spleen: Free Drainage: Recovery. PMID- 28998529 TI - Medical College Hospital.-An Enormous Elephantoid Tumour of the Scrotum; Successfully Removed. PMID- 28998531 TI - Insurance Office Fees. PMID- 28998533 TI - Bullet Wound of the Chest. PMID- 28998532 TI - Typhoid and Remittent Fevers. PMID- 28998534 TI - Official Paper. PMID- 28998535 TI - Report on the Health of the Troops Forming the Vitakri Field Force, and upon an Outbreak of Scurvy Amongst Them. PMID- 28998536 TI - Current Medical Topics. PMID- 28998537 TI - Indigenous Drugs. PMID- 28998538 TI - Memorandum on Famine Dietetics. PMID- 28998540 TI - On Sulphurous Acid as a Remedy for Cholera. PMID- 28998539 TI - The Cold Bath, and Affusion in Hyper-Pyrexia: Advantages Experienced in Cases of Remittent Fever. PMID- 28998541 TI - Post-Mortem Appearances after Hanging. PMID- 28998542 TI - Lithotomy Statistics in India. PMID- 28998543 TI - Hydro-Nephrosis. A Short Lecture to the Hospital Assistants of Akola District. PMID- 28998544 TI - 1879. PMID- 28998545 TI - Beri-Beri in the Mauritius. PMID- 28998546 TI - The Treatment of Opium-Eaters. PMID- 28998547 TI - On Large and Repeated Doses of Belladonna in Acute Intestinal Obstruction. PMID- 28998548 TI - My Contribution Towards a Clinical History of Hepatitis in India. A Personal Sketch. PMID- 28998549 TI - Medical News. PMID- 28998550 TI - On Examination for Colour-Blindness. PMID- 28998551 TI - A New Lithotomy Forceps. PMID- 28998553 TI - Dressings. PMID- 28998554 TI - The Calcutta Medical Society. PMID- 28998552 TI - Cases of Cholera Treated by the Hypodermic Injection of a Solution of Chloral Hydrate-(One Grain to Ten Minims of Water.). PMID- 28998556 TI - Current Medical Topics. PMID- 28998555 TI - Remarks on the So-Called Typho-Malarial Fevers and Their Treatment. PMID- 28998558 TI - Boracie Acid in Diphtheria. PMID- 28998557 TI - Remarks on Ignipedites. PMID- 28998559 TI - Penetrating Wound of the Thorax: Immediate Pneumocele: Excision of Portion of Lung: Recovery. PMID- 28998561 TI - The Calcutta Hospitals. PMID- 28998560 TI - Case of Loss of Function of the Chorda Tympani Nerve Resulting from Pressure of a Syphilitic Node in the Petrous Portion of the Temporal Bone: Rapid Cure. PMID- 28998562 TI - Arithmetical Pathology. PMID- 28998564 TI - Washing out the Uterine Cavity. PMID- 28998563 TI - A Case of Traumatic Tetanus; Recovery. PMID- 28998565 TI - The Nuddea Fever. PMID- 28998566 TI - Amputation of the Penis. PMID- 28998567 TI - Clinical Lecture on Haematocele: Delivered at the Medical College Hospital on the 2nd October 1883. PMID- 28998569 TI - Case of Foreign Body in the Nose for Seven Years; Persistent Neuralgia of One Half of the Face, Removal of the Body; Recovery. PMID- 28998568 TI - Case of Occlusion of the Vagina : Operation. PMID- 28998570 TI - Report of the Commission Appointed to Enquire into the Causes of the Epidemic Fever in Nuddea. PMID- 28998571 TI - An Interesting Case of Hydrocele in a European. PMID- 28998572 TI - On the Physiological and Medicinal Action of Hydrofluoric Acid and the Fluorides. PMID- 28998574 TI - The Causation and Treatment of Cholera. PMID- 28998575 TI - Current Medical Topics. PMID- 28998573 TI - Hypodermic Syringe Used for a Trocar and Canula in a Case of Hydrocele. PMID- 28998577 TI - Calcutta Medical Society. PMID- 28998576 TI - Contraction of Leg at a Right-Angle, Due to Abscess of the Thigh. PMID- 28998579 TI - On Malarious Urticaria. PMID- 28998578 TI - Paralysis after Fevers. PMID- 28998581 TI - Murchison Memorial. PMID- 28998580 TI - Sulphurous Acid in Cholera. PMID- 28998582 TI - The New Surgeon-General for Bengal. PMID- 28998583 TI - Two Cases of Abscess of the Liver. Case I.-Old Abscess: Operation: Recovery. Case II.-Old Abscess Masked by Ascites: Rupture: Death. PMID- 28998584 TI - Case of Ovarian Gestation. PMID- 28998585 TI - The Grant College Medical Society, Bombay. PMID- 28998586 TI - Cases Reported by Assistant-Surgeon Devendra Nath Roy. PMID- 28998587 TI - Cases Reported by Assistant-Surgeon Ram Kishen. PMID- 28998588 TI - Notes on Early Sanitation in India. PMID- 28998589 TI - Current Medical Topics. PMID- 28998590 TI - Kite-Flying. PMID- 28998592 TI - Case of Dislocation of Lens. PMID- 28998591 TI - Nature and Art in Disease. PMID- 28998593 TI - Medical News. PMID- 28998595 TI - Mr. Sanders and Lithotomy. PMID- 28998594 TI - Bengal Notes. PMID- 28998596 TI - Hospital Discpline. PMID- 28998597 TI - Sunstroke. PMID- 28998599 TI - Two Cases of Typhoid Fever Occurring among Prisoners in the Rupar Jail. PMID- 28998598 TI - Croup and Diphtheria. PMID- 28998600 TI - On the Use of an Aqueous Solution of Chlorine as a Deodorant. PMID- 28998602 TI - The Calcutta Medical College. PMID- 28998601 TI - Books on Hill Stations. PMID- 28998604 TI - Literature of Hill Stations and Climates. PMID- 28998603 TI - Continued Fever at Aden. PMID- 28998605 TI - Case Illustrating Long-Continued Suppression of Urine in Cholera with Ultimate Recovery. PMID- 28998606 TI - Xanthelasma. PMID- 28998607 TI - The Health of Calcutta in 1878. PMID- 28998609 TI - Medical News. PMID- 28998608 TI - Removal of a Large Fibro-Cystic Tumour from the Neck. PMID- 28998610 TI - Fever in the Punjab. PMID- 28998611 TI - Remarks on an Epidemic of Ague with Jaundice in the 15th Loodianah Sikhs at Kandahar in April 1879. PMID- 28998612 TI - Typhoid and Remittent Fever. PMID- 28998613 TI - Typhoid Fever in Cabul, Its Local Name and Treatment by Local Hakims. PMID- 28998615 TI - Correspondence Relating to the Use of "Cinchona Febrifuge" in the Treatment of Periodic Fevers. PMID- 28998614 TI - Meningitis, Associated with Local Paralysis and Gastric Ulcer. PMID- 28998616 TI - Cinchona Alkaloid. PMID- 28998617 TI - Introductory Lecture on the History of Anatomy in India, Delivered at the Opening of Session 1879-80. PMID- 28998618 TI - Sooree Charitable Dispensary, Compound Dislocation of Left Humerus at the Elbow; Reduction; Arthritis; Excision of Elbow Joint; Recovery. II.-Schirrous Cancer of the Breast and Involvement of an Axillary Gland; Extirpation and Enucleation; Recovery. PMID- 28998619 TI - Notes on Water Analysis; the Supply of Bhagulpore. PMID- 28998621 TI - A Remarkable Case of Sodomy. PMID- 28998620 TI - Report on the Outbreak of Cholera in the Bareilly Lunatic Asylum in April 1878. PMID- 28998623 TI - Fusiform Aneurism of Aorta and the Difficulty in Diagnosing It. PMID- 28998622 TI - Case of Glioma of Eyeball. PMID- 28998624 TI - Cases of Abscess of the Brain. PMID- 28998625 TI - Statement Showing the Results of the Major Surgical Operations Performed in the Dispensaries of the North-Western Provinces and Oudh, for the Year 1877. PMID- 28998626 TI - Chronic Obstruction of the Bowels with Stercoraceous Vomiting. PMID- 28998627 TI - Report on the Epidemic of Dengue of 1872, as It Appeared in Fort William, Calcutta. PMID- 28998628 TI - Fever in the Punjab. PMID- 28998629 TI - Hepatic Abcess, Simulating Ascites, and Complicated with Extensive Peritonitis; Symptoms of Addison's Disease and Tuberculosis. PMID- 28998630 TI - Medical News. PMID- 28998631 TI - Surgery in the North-Western Provinces. PMID- 28998633 TI - The Famine in the North-Western Provinces. PMID- 28998632 TI - Case of Dislocation of the Femur in an Infant. PMID- 28998634 TI - Tapi Muhrika Does Not Correspond with Any One Particular Fever of the Modern Nomenclature. PMID- 28998635 TI - The Plague in Russia. PMID- 28998636 TI - Chronic Starvation. PMID- 28998638 TI - Annual Report of the Agra Lunatic Asylum for 1878. PMID- 28998637 TI - Acute OEdema. PMID- 28998639 TI - The Immunity of Infants from Cholera. PMID- 28998641 TI - The Sanitary Condition of Dinagepore. PMID- 28998640 TI - Report on an Outbreak of Enteric Fever in B. Battery 2nd Brigade R. A. at Deesa, in August and September 1878. PMID- 28998642 TI - Medical News. PMID- 28998643 TI - Health of Calcutta during the 3rd Quarter of 1878. PMID- 28998644 TI - Cinchona Cultivation in Sikkim. PMID- 28998645 TI - Enteric Fever in Civil Practice. PMID- 28998646 TI - Foul Water and Dysentery. PMID- 28998647 TI - Case of Congenital Misplacement of the Intestines. PMID- 28998648 TI - Case of Eversion of Bladder. PMID- 28998649 TI - Sinuous Ulcer of the Knee, Causing Its Contraction; Forcible Extension, Followed by Rupture of the Popliteal Artery; Its Ligature Followed by Gangrene of the Leg; Amputation, and Recovery. PMID- 28998650 TI - Case of Acute Malarious Poisoning. PMID- 28998651 TI - Famine and Fecundity. PMID- 28998652 TI - Cholagogues. PMID- 28998653 TI - Poisoning in the North-Western Provinces, Oudh, and the Central Provinces. PMID- 28998654 TI - Cases of Frost-Bite in the Base Hospital, Quettah. PMID- 28998655 TI - Notes on a Case of Poisoning by Orpiment. PMID- 28998657 TI - The Health of the European Army in India in 1877. PMID- 28998656 TI - Medical News. PMID- 28998658 TI - Symptoms of Atropia Poisoning Following the Hypodermic Administration of the Drug. PMID- 28998660 TI - Report on the Epidemic of Dengue of 1872, as It Appeared in Fort William, Calcutta. PMID- 28998659 TI - Fever in the Punjab. PMID- 28998661 TI - Narrative of the March of the 15th Loodianah Sikhs, from Sailkote to Kandahar. PMID- 28998662 TI - Acute Malarial Poisoning: Death in 24 Hours. PMID- 28998663 TI - Is Acute Dropsy (the New Disease) Contagious? PMID- 28998664 TI - Case of Imperforate Anus, &c. PMID- 28998665 TI - Health Statistics of the Native Army. PMID- 28998666 TI - Case of Asphyxia Caused by Post Pharyngeal Abscess; Resusctation by Evacuation, and Howard's Direct Method of Artificial Respiration. PMID- 28998667 TI - Typhoid and Remittent Fevers. PMID- 28998668 TI - Some Remarks on the Relation of Filaria Sanguinis Hominis to Chyluria and Other Lymphoid Diseases. PMID- 28998669 TI - Casualties in the 4th Punjab Cavalry and 4th Sikh Infantry during the Recent Disturbances in the Dera Ismael Khan District. PMID- 28998670 TI - Case of Draining the Cavity of the Peritoneum. PMID- 28998671 TI - Pneumatic Aspiration; Puncture of Parenchymatous Organs; Direct Depletion. PMID- 28998672 TI - Cholera and Pilgrims. PMID- 28998673 TI - Medical News. PMID- 28998674 TI - Clinical Lecture on Synovitis and Granular Disease of the Synovial Membrane- Pulpy Degeneration; Scrofulous Synovitis. PMID- 28998675 TI - On Iridectomy in Certain Complications of Iritis. PMID- 28998676 TI - The Army Sanitary Commission on Typhoid Fever in India. PMID- 28998677 TI - Current Medical Notes. PMID- 28998678 TI - Continued Fever at Aden. PMID- 28998679 TI - Accident with Tr. Iodi. PMID- 28998680 TI - Medical College Hospital. PMID- 28998681 TI - Medicos Advertizing in Bombay. PMID- 28998683 TI - Chloroform. Part of a Lecture Delivered at the Medical College. PMID- 28998682 TI - Madras Lunatic Asylums. PMID- 28998684 TI - Vegetable Germs and Disease. PMID- 28998685 TI - Cases of Lithotomy. PMID- 28998686 TI - An Attack of Angina Pectoris Brought on by Rice and Milk Diet. PMID- 28998688 TI - Report of the Chemical Analyser, Bombay, for 1877-78. PMID- 28998687 TI - Official Report on an Outbreak of Fever at the Nira Canal Camp. PMID- 28998690 TI - Hedysarum Gangeticum in Dysentery. PMID- 28998689 TI - Famine Pathology. PMID- 28998691 TI - Medical News. PMID- 28998692 TI - Cases of Abscess in the Liver Treated in the Mayo Native Hospital during 1878. PMID- 28998693 TI - The Cause of Cholera. PMID- 28998694 TI - Operation for Entropium and Trichaisis. PMID- 28998695 TI - Caustic Potash in the Treatment of Carbuncle. PMID- 28998696 TI - Case of Fracture of the Skull. PMID- 28998697 TI - A Record of Ophthalmic Practice in Oudh. PMID- 28998698 TI - Case of Multiple Vesical and Urethral Calculi. PMID- 28998699 TI - Bombay Lunatic Asylums. PMID- 28998700 TI - Remarks on the "Case of Fatal Thermal Fever(?) by Surgeon-Major G. C. Gribbon, M. B., A. M. D." PMID- 28998701 TI - Scarlatina in Calcutta. PMID- 28998702 TI - Case of Urethro-Vesical Calculus. PMID- 28998704 TI - Management of Habitual Catarrah. PMID- 28998703 TI - The Calcutta Hospitals. PMID- 28998706 TI - Dharmsala. PMID- 28998705 TI - A Case of Abscess of the Liver Treated by Aspiration. PMID- 28998707 TI - Report on Dengue in Howrah District during 1872. PMID- 28998708 TI - Apoplectic Trance, or Perfect Coma of 18 Days' Duration, Followed by Recovery. PMID- 28998710 TI - The Localization of Cerebral Disease. PMID- 28998709 TI - Health of the Native Army in 1877. PMID- 28998711 TI - Medical Education in Ceylon. PMID- 28998712 TI - Fever in the Punjab. PMID- 28998713 TI - Salicylic Acid in Neuralgia. PMID- 28998714 TI - Wanted-Skulls. PMID- 28998715 TI - Mayo Native Hospital-I.-Aneurism of the Femoral Artery; Ligature of External Iliac: Recovery. II.-A Case of Ovarian Tumour: Ovariotomy: Recovery. PMID- 28998717 TI - Nervous Diffusion. PMID- 28998716 TI - Depressed Comminuted Fracture of the Skull; Trephining; Recovery. PMID- 28998718 TI - An Action for the Recovery of Fees. PMID- 28998719 TI - Literature of Hill Stations and Climates. PMID- 28998720 TI - Amputation of the Penis. PMID- 28998721 TI - Remarks on Imperforate Anus. PMID- 28998722 TI - Fourteen Months' Lithotomy Operations in Rohilkhund. PMID- 28998723 TI - Medical College Hospital-Case of Glandular Sarcoma of the Neck; Removal; Death from Paeymia. PMID- 28998725 TI - Medical News. PMID- 28998724 TI - Narrative of the March of the Right Wing, 15th Loodianah Sikhs, from Sukkur until They Joined the Regimental Head-Quarters at Kandahar. PMID- 28998726 TI - 1878. PMID- 28998727 TI - A Wound of the Scalp, with Traumatic Tetanus. PMID- 28998728 TI - Medical News. PMID- 28998729 TI - A Record of Ophthalmic Practice in Oudh. PMID- 28998730 TI - A Few Observations on Enteric or Typhoid Fever: Apropos of a Report on the Same in Relation to British Troops in the Madras Command. PMID- 28998731 TI - Excision of Lateral Half of Lower Jaw. PMID- 28998732 TI - Three Cases of Goitre. PMID- 28998733 TI - A Case of Primary Adenitis under the Care of Surgeon J. C. Lucas, M. D., F. R. C. S. PMID- 28998734 TI - Acute Dropsy (Beriberi?.). PMID- 28998735 TI - Case of Impassable Stricture of the Urethra with Vesico-Rectal and Perineal Fistula and Stones in the Prostatic Portion of the Urethra: Partial Recovery. PMID- 28998737 TI - On the Detection of Magnesic-Chloride in Portable-Waters. PMID- 28998736 TI - A Case of Typhoid Lesion Confined to the Large Intestine, and Some Remarks on the Causation of the Disease. PMID- 28998739 TI - Inguinal Abscess: Communication with Abdominal Cavity and Peritonitis after Operation: Recovery. PMID- 28998738 TI - Report on Cases of Fever Treated by "Eucalyptus Globulus" in Dehree, from June 17th to October 17th, 1878. PMID- 28998740 TI - Modified Wood's Operation after Reduction of Strangulated Hernia. PMID- 28998741 TI - A Case of Vesical Calculus; Lateral Lithotomy: Recovery. PMID- 28998742 TI - Two Successful Cases of Excision of the Lower Jaw for Myeloid Tumour, with Remarks. PMID- 28998743 TI - "The Functional(?) Derangement of the Circulatory System in European Soldiers in the Hot Weather. PMID- 28998744 TI - Gauhati Dispensary.-Case of Opium Poisoning: Recovery. PMID- 28998745 TI - Observations on the Operation of Lithotomy. PMID- 28998746 TI - Treatment of Opium-Eaters. PMID- 28998748 TI - A Case of Intravenous Injection of Milk. PMID- 28998747 TI - Lectures on Diseases of Joints. PMID- 28998750 TI - Medical News. PMID- 28998749 TI - A Case of Protracted Labor Attended with Convulsions: Delivery by Forceps: Recovery. PMID- 28998751 TI - Case of Obstruction of the Bowels. PMID- 28998753 TI - Notes on Early Sanitation in India. PMID- 28998752 TI - Report on the Use of Apomorphia in Sunstroke. PMID- 28998755 TI - Current Medical Topics. PMID- 28998754 TI - Case of Scirrhus Cancer of Mesentery. PMID- 28998756 TI - Memorandum on Famine Dietetics. PMID- 28998757 TI - Sanitation in Bengal. PMID- 28998758 TI - Case of Cancerous Tumour of Upper Jaw: Removal, and Temporary Recovery. PMID- 28998759 TI - Surgeon-General Gordon's Prize. PMID- 28998760 TI - Report on Scurvy and Chronic Rheumatism (Scorbutus and Myalgia) as It Occurred in the 1st Infantry H. C. at Lingsugoor in 1878. PMID- 28998761 TI - Nurses in Zululand. PMID- 28998762 TI - The Ceylon Medical School. PMID- 28998763 TI - Notes on Early Sanitation in India. PMID- 28998764 TI - Cinchona Febrifuge in Malarious Fevers. PMID- 28998765 TI - Calculus, Vesical, in a Hermaphrodite: Lithotomy: Recovery. PMID- 28998766 TI - Medical News. PMID- 28998767 TI - Current Medical Topics. PMID- 28998768 TI - Compound Fracture of Left Humerus with Compound Dislocation of Left Elbow-Joint: Traumatic Gangrene: Amputation below Shoulder: Recovery. PMID- 28998770 TI - Medical Education. PMID- 28998769 TI - Remarks, and Notes on Tetanus. PMID- 28998772 TI - The Calcutta Medical Society. PMID- 28998771 TI - Memorandum on Famine Dietetics. PMID- 28998773 TI - Notes Sur Le Cholera Du Village DeVadakencoulam En Decembre 1877. PMID- 28998774 TI - The Medical Services and the Affghan War. PMID- 28998775 TI - Notes on Aspirating and Aspirators. PMID- 28998776 TI - Current Medical Topics. PMID- 28998777 TI - Croup and Diphtheria. PMID- 28998778 TI - Medical News. PMID- 28998779 TI - A Case of Morphia Poisoning Successfully Treated with Hypodermic Injection of Sulphate of Atropia. PMID- 28998780 TI - Case of Congenital Hydrocephalus. PMID- 28998781 TI - Indigenous Drugs. PMID- 28998782 TI - Bengal Notes. PMID- 28998784 TI - The Mayo Hospital, Lahore. PMID- 28998783 TI - Enteric Fever among Natives. PMID- 28998785 TI - Hospital of the 10th N. I.-Case of Profuse Sweating of Hands and Feet with Anaesthesia. PMID- 28998786 TI - On the Diagnosis between Enteric or Typhoid Fever and Remittent or Intermittent Fever. PMID- 28998787 TI - Insurance Office Fees. PMID- 28998788 TI - Medical College Hospital-Case of Compound Comminuted Fracture of Thigh, &c.; Amputation; Death in 75 Hours; Dissection of Aseptic Stump and Colles's Fracture of Right Radius. PMID- 28998790 TI - Cancrum Oris in an European Soldier; Enlarged Spleen; Pancreatic Disease Post Mortem Results. PMID- 28998789 TI - Partabgarh Dispensary.-Cases of Intestinal Obstruction. PMID- 28998791 TI - Malposition of Organs in a Human Body. PMID- 28998792 TI - Report on Acute Anaemic Dropsy in Mauritius. PMID- 28998793 TI - A Case of Hepatic Abscess, with Remarks. PMID- 28998795 TI - Current Medical Topics. PMID- 28998794 TI - The Treatment of Snake-Bite. PMID- 28998796 TI - 1881. PMID- 28998797 TI - Two Cases of Hydrorrhoea Gravidorum. PMID- 28998798 TI - The Calcutta Medical Society. PMID- 28998799 TI - The Ductless Glands. PMID- 28998800 TI - Some Surgical Operations and Other Cases. PMID- 28998801 TI - Experiments with Permanganate of Potash in Snake-Poisoning. PMID- 28998802 TI - The Treatment of Leprosy with Gurjun Oil. PMID- 28998803 TI - On Epidemics of Dengue Fever, Their Diffusion and Etiology. PMID- 28998805 TI - Notes on Dr. Wall's Monograph on Cobra and Daboia Poisons. PMID- 28998804 TI - A Vindication. PMID- 28998807 TI - Cholera and Filth. PMID- 28998806 TI - Current Medical Topics. PMID- 28998808 TI - Cases Illustrating the Use of Infrequent Antiseptic Dressing. PMID- 28998809 TI - The Eden Hospital for Women and Children. PMID- 28998810 TI - Clinical Lecture on the Direct Operation for the Cure of Hernia: Delivered on the 15th August 1882 at the Medical College Hospital. PMID- 28998811 TI - The Calcutta Medical Society. PMID- 28998812 TI - Resection of the Long Bones. PMID- 28998813 TI - The Indore Charitable Hospital. PMID- 28998814 TI - Current Medical Topics. PMID- 28998815 TI - Cases from the Purulia Dispensary. PMID- 28998816 TI - Case of Aneurism of Aorta. PMID- 28998818 TI - A Record of Ophthalmic Practice in Gurhwal, N. W. P. PMID- 28998817 TI - Valvular Disease of Heart with Embolism of the Cerebral and Posterior Tibial Arteries. PMID- 28998820 TI - Tetanus in Parturient Women. PMID- 28998819 TI - A Plea for Malaria. PMID- 28998821 TI - Snake-Bite; Recovery. PMID- 28998823 TI - Medical News. PMID- 28998822 TI - Precis of Operations Performed in the Wards of the First Surgeon, Medical College Hospital, during the Year 1881. PMID- 28998825 TI - The Treatment of Acute Rheumatism by the Salicylates. PMID- 28998824 TI - Compound Dislocation of Inferior Angle of Scapula Together with Severe Lacerated Wounds Caused by a Bear; Excision of Inferior Angle of Scapula with Recovery. PMID- 28998826 TI - Pay of the Subordinate Medical Department. PMID- 28998827 TI - The Pay of Junior Medical Officers. PMID- 28998828 TI - A Case of Traumatic Gangrene Following Compound Fracture of the Right Leg. PMID- 28998830 TI - Case of Tumour of the Bladder (in the Male) Successfully Removed through a Perineal Section of the Urethra. PMID- 28998829 TI - Death from Chloroform. PMID- 28998831 TI - The Calcutta Medical Society. PMID- 28998832 TI - The Tubercle Bacillus. PMID- 28998833 TI - Hydrobromic Acid. PMID- 28998834 TI - The Dublin Murder; Medical Evidence at the Inquest. PMID- 28998835 TI - Medical News. PMID- 28998836 TI - Child-Mortality by Dr. Pfeiffer of Weimar. PMID- 28998837 TI - A Case of Snake-Bite: Hypodermic Injection of Permanganate of Potash. PMID- 28998839 TI - Current Medical Topics. PMID- 28998838 TI - Delirium Tremens as a Complication in Acute Diseases. PMID- 28998840 TI - Report on Epidemic Fever in Buxar. PMID- 28998841 TI - Cases of Fever Treated Successfully by Hypodermic Injection of Bromine of Quinine. PMID- 28998842 TI - Fracture and Wound of the Leg Followed by Tetanus. PMID- 28998843 TI - The Calcutta Medical Society. PMID- 28998844 TI - Hydrophobia: Its Pathology and Prevention. PMID- 28998845 TI - The Origin of Enteric Fever. PMID- 28998846 TI - Topographical Report on the Andaman Islands and Port Blair. PMID- 28998847 TI - Case of Dislocation of Hip-Joint; Reduction. PMID- 28998848 TI - Hydrophobia. PMID- 28998849 TI - Report of Surgical Operations Performed at the Mayo Hospital, Lahore, during January, February and March 1882. PMID- 28998850 TI - Case from Hospital Practice. PMID- 28998851 TI - Medical News. PMID- 28998852 TI - The Calcutta Medical Society. PMID- 28998854 TI - The Mortality of Indian Jails. PMID- 28998853 TI - Precis of Operations Performed in the Wards of the First Surgeon, Medical College Hospital, during the Year 1881. PMID- 28998855 TI - Retention of Urine-Extravasation-Operation-Recovery. PMID- 28998856 TI - Current Medical Topics. PMID- 28998857 TI - Notes of Post-Mortem Examination of a Case Which Formed the Subject of Judicial Enquiry. PMID- 28998858 TI - Notes on Dengue Fever. PMID- 28998859 TI - Cholera and Fever Poisons. PMID- 28998860 TI - A Case of Spurious Hermaphroditism. PMID- 28998862 TI - A Case of Cholera. PMID- 28998861 TI - Leiter's Pliable Metal Temperature Regulators. PMID- 28998863 TI - Medical News. PMID- 28998864 TI - Notes of a Case of Aconite Poisoning, Treated at Kasauli. PMID- 28998865 TI - Tripathy Kumpryng Hospital, Gurhwal: Case of Lithotomy. PMID- 28998866 TI - Notes on Indigenous Vegetable Poison Seeds of the Abrus Precatorius. PMID- 28998867 TI - Papaw-Carica Papaya, L.: From New Commercial Plants and Drugs. PMID- 28998868 TI - Ten Cases of Lithotrity at One Sitting. PMID- 28998870 TI - Current Medical Topics. PMID- 28998869 TI - A Case of Intestinal Obstruction. PMID- 28998871 TI - Pilocarpine. PMID- 28998872 TI - A Rhino-Plastic Operation.-Recovery. PMID- 28998873 TI - How Cholera Is Bred and Spread. PMID- 28998874 TI - A Case of Traumatic Tetanus from Practice. PMID- 28998875 TI - Bareilly Dispensary: Two Cases of Severe Injury to the Head. PMID- 28998877 TI - On Scrofula, Tuberculosis, and Phthisis in India. PMID- 28998876 TI - Diagnosis Wanted. PMID- 28998878 TI - Calcutta Medical Society. PMID- 28998879 TI - Treatment of Cholera with Sulphurous Acid. PMID- 28998880 TI - Etawah Sudder Dispensary: Case of Obstruction of the Bowels. PMID- 28998881 TI - Pestilentia-Pali Plague-Mahamurree. PMID- 28998882 TI - On Epidemic Catarrah as It Occurred in the Jhang Jail in May 1881. PMID- 28998883 TI - Remarks on the Subject of Micro-Organisms in Disease: Read before the Gwalior District Medical Society. PMID- 28998884 TI - The Bengal Medical Service in 1782. PMID- 28998885 TI - Uncomfortable Effects of Quinine. PMID- 28998886 TI - The Bacillus Malariae. PMID- 28998887 TI - The Climate of Indian Hill-Sanitaria: Is It Beneficial in Scrofula, Tuberculosis, and Phthisis?(a). PMID- 28998888 TI - On the Prevalence of Enteric Fever among Young Soldiers in India. PMID- 28998891 TI - Statistics of Operations at the Necker Hospital. PMID- 28998889 TI - On Epidemics of Dengue Fever; Their Diffusion and Etiology. PMID- 28998890 TI - Clinical Notes of Two Cases of Injuries to the Head. PMID- 28998893 TI - Current Medical Topics. PMID- 28998892 TI - Experiments with Permanganate of Potash in Snake-Poisoning. PMID- 28998895 TI - Medical News. PMID- 28998894 TI - The Calcutta Medical Society. PMID- 28998896 TI - The Penal Settlement of Port Blair. PMID- 28998897 TI - Case of Fibro-Cellular Tumour. PMID- 28998898 TI - Treatment of Typhoid Fever by Salicylate of Soda. PMID- 28998899 TI - Codeia in Diabetes. PMID- 28998900 TI - Dress of Apothecary Class, S. M. Department. PMID- 28998901 TI - The "Parangi Disease" of Ceylon. PMID- 28998902 TI - Malaria. PMID- 28998904 TI - Reduction of Dislocation by Manipulation. PMID- 28998903 TI - A Very Interesting Case of Hysterical Heptalgia Simulating Suppurative Hepatitis and Terminating in Hystero-Epilepsy: Hysteria in a Male. PMID- 28998905 TI - Proceedings of the Gwalior District Medical Society. PMID- 28998906 TI - Report on the Treatment of Acute Dysentery by Aconite Based on One Hundred and Fifty-One Cases. PMID- 28998907 TI - Experiments with Permanganate of Potash in Snake-Poisoning. PMID- 28998908 TI - Nitrogenous Waste in the Blood and Its Probable Use. PMID- 28998910 TI - A Specific for Eczema. PMID- 28998909 TI - The Health of the European Army of India in 1880. PMID- 28998911 TI - A Nematoid Haematozoon in a Camel. PMID- 28998912 TI - Current Medical Topics. PMID- 28998913 TI - The Delivery of the Placenta. PMID- 28998914 TI - The Calcutta Medical Society. PMID- 28998915 TI - A Case of Chyluria Treated with Benzoic Acid. PMID- 28998916 TI - The Pre-Cancerous Stage of Cancer, and the Importance of Early Operations. PMID- 28998918 TI - Dress of the S. M. D. PMID- 28998917 TI - Micro-Organisms or Granules of Bizzozero in the Blood. PMID- 28998919 TI - On Insolation or Sunstroke. PMID- 28998920 TI - The Hypodermic Injection of Quinine as a Prophylactic against Cholera. PMID- 28998921 TI - Case of Penetrating Wound of the Abdomen. PMID- 28998922 TI - Hydrangea. PMID- 28998923 TI - Penetrating Gunshot Wound of Chest: Recovery. PMID- 28998924 TI - Pyaenia. PMID- 28998925 TI - The A. M. D. PMID- 28998926 TI - Some Remarks on Surgeon M. D. O'Connells Article on "Nitrogenous Waste in the Blood and Its Probable Use." Which Appeared in the "Indian Medical Gazette" for April 1882. PMID- 28998928 TI - Women Doctors for India. PMID- 28998927 TI - "Cholera Fever" in Amritsar. PMID- 28998929 TI - Medical News. PMID- 28998930 TI - Enquiry. PMID- 28998931 TI - The Calcutta Medical College. PMID- 28998932 TI - Lance Wound of Face. PMID- 28998933 TI - On the Treatment of Toothache Arising from Dental Caries, and on a Simple Method of Stopping Teeth. PMID- 28998934 TI - Ovariotomy. PMID- 28998935 TI - Extreme Physiological Action of Sulphate of Quinine. PMID- 28998936 TI - Notes on a Case of Puerperal Fever. PMID- 28998937 TI - Indore Charitable Hospital.-A Case of Sciatica Treated by Nerve Stretching. PMID- 28998938 TI - The Artificial Feeding of Infants. PMID- 28998939 TI - Specificity in Disease. PMID- 28998941 TI - The Calcutta Medical Society. PMID- 28998940 TI - On the Use of Antiseptic Dry and Infrequent Dressings. PMID- 28998943 TI - Current Medical Topics. PMID- 28998942 TI - Current Medical Topics. PMID- 28998944 TI - Amaranthus Spinosa. PMID- 28998945 TI - Notes of a Case of Hydrocele of the Spermatic Cord, Complicated with Symptoms of Strangulated Hernia. PMID- 28998946 TI - Ophthalmic Notes. PMID- 28998947 TI - A Case of Craniotomy. PMID- 28998948 TI - Report of Surgical Operations during the Second Quarter of 1882. PMID- 28998949 TI - Note on Malarial Fever. PMID- 28998951 TI - Notes on Feeding Cholera Patients: Reprinted from the Edinburgh Medical Journal for November 1881. PMID- 28998950 TI - Srinagur Hospital, Gurhwal. PMID- 28998952 TI - Treatment of the Uric Acid Diathesis. PMID- 28998954 TI - Report on an Outbreak of Cholera in the Lahore Central Jail in August 1881. PMID- 28998953 TI - Tapping the Bowel. PMID- 28998956 TI - Medical Practice in Calcutta. PMID- 28998955 TI - Combined Use of Morphia and Chloroform. PMID- 28998957 TI - The Hypodernire Injection of Quinue in Cholera. PMID- 28998958 TI - Medical News. PMID- 28998959 TI - A Case of Traumatic Tetanus and Death, under Dr. Halpin. PMID- 28998961 TI - The Calcutta Medical Society. PMID- 28998960 TI - Further Experiments with Permanganate of Potash, Liq. Potassae, and Iodine in Cobra-Poisoning. PMID- 28998962 TI - A Few Cases from Upper Assam. PMID- 28998964 TI - Current Medical Topics. PMID- 28998963 TI - Peshawar Branch Dispensary: Wound of the Heart. PMID- 28998965 TI - Cases of Hernia Cerebri. PMID- 28998966 TI - Medical News. PMID- 28998967 TI - Case of Snake-Bite: Recovery. PMID- 28998968 TI - Pestilentia-Pali Plague-Muahamrree. PMID- 28998969 TI - A Charge of Manslaughter against a Medical Man. PMID- 28998970 TI - The Calcutta Medical Society. PMID- 28998971 TI - Notes from Memory of a Case of Perforating Ulcer of Duodenum. PMID- 28998972 TI - A Case of Splenic Abscess Treated in the Durbhunga Raj Hospital. PMID- 28998973 TI - Case of Death from Snake-Bite. PMID- 28998974 TI - Partial Resection of the Lungs. PMID- 28998975 TI - A Case of Cobra-Bite, with Remarks. PMID- 28998976 TI - Post-Mortem Examinations. PMID- 28998977 TI - The Amritsar Fever. PMID- 28998978 TI - Clinical Lecture on the Operation for Removal of Scrotal Elephantiasis: Delivered on the 10th October 1882, at the Medical College Hospital. PMID- 28998979 TI - Notes on Indigenous Vegetable Poisons- Seeds of the Abrus Precatorius. PMID- 28998981 TI - The Indore Charitable Hospital. PMID- 28998980 TI - Sind Boil: Suppuration. PMID- 28998982 TI - Bovine Post-Mortem Examinations by Medicai Men. PMID- 28998984 TI - The Disposal of Sewage: No. I. PMID- 28998983 TI - A Case of Right-Sided Hemiplegia with Aphasia: Recovery. PMID- 28998986 TI - Medical News. PMID- 28998985 TI - A Case of Lumbo-Abdominal Neuralgia, Treated with Sulphuric AEther and Belladonna. PMID- 28998987 TI - Measures to Be Adopted against Pollution of the Soil by Cesspools. PMID- 28998988 TI - Nitro-Glycerin in Puerperal Convulsions. PMID- 28998989 TI - Carbolic Acid in Cholera. PMID- 28998990 TI - Current Medical Topics. PMID- 28998991 TI - Clinical Lecture on the Direct Operation for the Cure of Hernia: Delivered on the 22nd August 1882, at the Medical College Hospital. PMID- 28998992 TI - The Treatment of the Uric Acid Diathesis. PMID- 28998994 TI - Miscellaneous Jottings from Daily Practice. PMID- 28998993 TI - Notes on Dr. Wall's Monograph on Cobra and Daboia Poisons. PMID- 28998995 TI - Diagnosis Wanted. PMID- 28998996 TI - Pay of the Subordinate Medical Department. PMID- 28998997 TI - Tincture of Iodine and Burnt Alum in Intermitent Fever. PMID- 28998999 TI - Erratum. AB - [This corrects the article on p. 176 in vol. 17.]. PMID- 28998998 TI - The Calcutta Medical Society. PMID- 28999000 TI - A Case of Acute Mania. PMID- 28999001 TI - Notes on False Point. PMID- 28999002 TI - Women Doctors in Russia. PMID- 28999003 TI - Bovine Post-Mortem Examinations, by Medical Men. PMID- 28999004 TI - Case of Snake-Bite: Treatment with Permanganate of Potash. PMID- 28999005 TI - Report on a Case of Cholera. PMID- 28999006 TI - Case of Compound Depressed Fracture of Skull. PMID- 28999008 TI - Enteric and Other Fevers in Afghanistan. PMID- 28999007 TI - Medical Department-Pensions. PMID- 28999009 TI - Death by Entrance of Air or Gas into the Right Heart. PMID- 28999010 TI - Three Cases of Poisoning by the Fruit of Cheena Kuroopee, Natural Order Apocynaceae-One Proving Fatal. PMID- 28999012 TI - Current Medical Topics. PMID- 28999011 TI - Ruttesing Hospital, Ahmedabad. PMID- 28999013 TI - The Calcutta Medical Society. PMID- 28999014 TI - Iron Biscuits. PMID- 28999015 TI - Medical News. PMID- 28999017 TI - Consumption as a Contagious Disease. PMID- 28999016 TI - Report on Some Case of Scarlet Fever 8th K. R. I. Hussars. PMID- 28999018 TI - A Case of Hypospadias with Great Deficiency of Corpus Spongiosum. PMID- 28999019 TI - Child-Mortality by Dr. Pfeiffer of Weimar. PMID- 28999020 TI - The Treatment of Acute Pneumonia by Large Doses of Belladonna. PMID- 28999021 TI - Precis of Operations Performed in the Wards of the First Surgeon, Medical College Hospital, during the Year 1880. PMID- 28999023 TI - Srinagar Dispensary, Gurhwal.-A Case of Pinash. PMID- 28999022 TI - Traumatic Tetanus. PMID- 28999025 TI - Cholera and Pilgrims. PMID- 28999024 TI - A Case of Fibroid Tumour of the Neck Weighing 51/4 Lbs.: Excision: Recovery. PMID- 28999026 TI - Treatment of Opium-Eaters. PMID- 28999027 TI - Case of Fracture of Skull. PMID- 28999028 TI - Kurchicine in Acute Dysentery. PMID- 28999029 TI - The Hygiene and Etiological Import of Relapse in Enteric Fever: And Dr. Irvine. PMID- 28999030 TI - Report on the Outbreak of Beri-Beri in the Criminal Prison, Singapore. PMID- 28999031 TI - Tapeworm. PMID- 28999032 TI - My Contribution towards a Clinical History of Hepatitis in India-A Personal Sketch. PMID- 28999033 TI - A Case of Fracture of Both Thighs, One Being Comminuted: Recovery without Shortening of Either Leg. PMID- 28999034 TI - Acute Bronchocele. PMID- 28999036 TI - The Calcutta Medical Society. PMID- 28999035 TI - Snake-Poisoning and Its Treatment. PMID- 28999038 TI - Medical News. PMID- 28999037 TI - Abstract of a Clinical Lecture on Amputation, Delivered on the 1st of February 1881. PMID- 28999039 TI - Lithotomy. PMID- 28999041 TI - Current Medical Topics. PMID- 28999040 TI - Hygiene of Indian Prisons. PMID- 28999042 TI - Treatment of Opium-Eaters. PMID- 28999043 TI - A Medical Sketch of Inland Emigration Operations from 1863-64 to 1879-80. PMID- 28999044 TI - Some Notes on the Different Diseases Diagnosed as Fever in the General Hospital at Madras. PMID- 28999045 TI - Civil Hospital Assistants. PMID- 28999046 TI - The Calcutta Medical Society. PMID- 28999047 TI - The Cholera of 1873 in Germany. PMID- 28999049 TI - Medical News. PMID- 28999048 TI - Cholera Amongst Emigrants to the Tea Districts. PMID- 28999051 TI - Bhagulpore Hospital. Case of Traumatic Tetanus after Compound Fracture of Forearm: Hypodermic Injection of Atropiae Sulphas: Recovery. PMID- 28999050 TI - Papaya Juice. PMID- 28999053 TI - Partabgarh Dispensary. Cases Recorded. PMID- 28999052 TI - Current Medical Topics. PMID- 28999054 TI - Analysis of Liebig's Chemical Food, or Wine of Phosphates. PMID- 28999055 TI - A Case of Suppression of Urine in Which Symptoms of Uraemic Poisoning Did Not Develop for 13 Days. PMID- 28999056 TI - My Contribution towards a Clinical History of Hepatitis in India-A Personal Sketch. PMID- 28999057 TI - Note of a Case of Heteradelphic Monstrosity. PMID- 28999059 TI - Report on the Outbreak of Beri-Beri in the Criminal Prison, Singapore. PMID- 28999058 TI - Cholera and Pilgrims. PMID- 28999060 TI - Srinagar Dispensary, Garhwal. A Case of Traumatic Gangrene Supervening on Compound Fracture of the Right Humerus: Amputation at Shoulder Joint: Recovery. PMID- 28999061 TI - Cases Treated by Assistant-Surgeon A. C. Kastagir. PMID- 28999062 TI - On the Hygiene of Indian Prisons. PMID- 28999064 TI - Charitable Dispensaries in the N. W. Provinces and Oudh. PMID- 28999063 TI - Ignipedites. PMID- 28999065 TI - Ligature of the Right Common Carotid Artery for Supposed Aneurism, the Tumour Really Being Pulsating Encephaloid. PMID- 28999066 TI - Fungus Disease-Recurrence after Amputation. PMID- 28999067 TI - Cobra-Bite: Immediate Treatment. PMID- 28999068 TI - Compound Complicated Fracture of Left Humerus at the Elbow-Joint: Primary Amputation: Recovery. PMID- 28999069 TI - Some Remarks on Leprosy. PMID- 28999070 TI - My Contribution towards a Clinical History of Hepatitis in India-A Personal Sketch. PMID- 28999071 TI - Lithotrity with Rapid Evacution of the Debris. PMID- 28999072 TI - Beri-Beri. PMID- 28999073 TI - The Monthly Official Army List. PMID- 28999074 TI - The Treatment of Opium-Eaters. PMID- 28999075 TI - A Medico-Topographical Report of Sambalpur, Central Provinces. PMID- 28999076 TI - A Case of Ventral Hernia. PMID- 28999077 TI - Medical News. PMID- 28999078 TI - Some Notes on the Different Diseases Diagnosed as Fever in the General Hospital at Madras. PMID- 28999079 TI - Current Medical Topics. PMID- 28999080 TI - The Calcutta Medical Society. PMID- 28999082 TI - The Punjab Medical College. PMID- 28999081 TI - Case of Osteo-Sarcoma. PMID- 28999083 TI - The Effects of a Reduced Jail Dietary. PMID- 28999085 TI - A Medical Sketch of Inland Emigration Operations from 1863-64 to 1879-80. PMID- 28999084 TI - Refrigerating Apparatus. PMID- 28999086 TI - Case of Resection of Tibia. PMID- 28999088 TI - The Abortive Treatment of Syphilis. PMID- 28999087 TI - Precis of Operations Performed in the Wards of the First Surgeon. Medical College Hospital, during the Year 1883. PMID- 28999090 TI - Some Notes on the Poison Contained in Choleraic Alvine Discharges. PMID- 28999089 TI - Calcutta Medical Society. PMID- 28999092 TI - Current Medical Topics. PMID- 28999091 TI - How Is Criminal Abortion Brought on in India? PMID- 28999093 TI - How Are Newly-Born Illegitimate Children Killed in India? PMID- 28999095 TI - A Case of Dermatolysis or Pachydermatocele. PMID- 28999094 TI - A Case of Kidney Disease Including Hypertrophy of Heart and Haemorrhage into the Brain. PMID- 28999097 TI - Cholera in Egypt: Reprinted from the "Medical Times and Gazette". PMID- 28999096 TI - Placenta Previa Unavoidable Haemorrhage. PMID- 28999099 TI - Dr. Couvidon's Report to the French Government on the Cholera in Egypt. PMID- 28999098 TI - On the Radical Cure of Hernia. PMID- 28999101 TI - Calcutta Medical Society. PMID- 28999100 TI - Current Medical Topics. PMID- 28999102 TI - Notes on the Surgical Treatment of Liver Abscess in Dispensary Practice-Results of 14 Cases. PMID- 28999103 TI - Notes of a Few Operations Performed at the Delhi Civil Hospital. PMID- 28999104 TI - Antiseptic Dressing. PMID- 28999106 TI - The Census of Bengal. PMID- 28999105 TI - Clinical Lecture on Herniotomy: Delivered at the Medical College Hospital on the 8th of January, 1884. PMID- 28999107 TI - Three Cases of Excision of the Tongue by Scissors. PMID- 28999108 TI - Abstracts and Extracts. PMID- 28999109 TI - Current Medical Topics. PMID- 28999110 TI - Dr. Vincent Richards' Experiments with Cholera Stools. PMID- 28999111 TI - On the Treatment of Small-Pox and Chicken-Pox by the External Application of Calcium Sulphide Lotion. PMID- 28999113 TI - Supplementary Notes on the Specific Poison Contained in Choleraic Alvine Discharges. PMID- 28999112 TI - Removal of Very Large Fatty Tumour. PMID- 28999114 TI - Complete Absence of Rectum. Colotomy. PMID- 28999116 TI - The Treatment of Simple and Sloughing Dysentery by Large Doses of Ipecacuanha. PMID- 28999115 TI - Litholapaxy in Male Children. PMID- 28999117 TI - The Cholera Bacillus. PMID- 28999118 TI - Amputation of Thigh for Scrofulous Disease of Knee Joint. Union by First Intention. PMID- 28999119 TI - Medical Societies. PMID- 28999120 TI - Operative Treatment of Cancer of Penis. PMID- 28999121 TI - Galvanism in Cholera Collapse. PMID- 28999123 TI - Cancerous Tumour of Tongue: Excision. PMID- 28999122 TI - Cases of Ulcer Occurring Amongst the XVth Sikhs at Delhi. PMID- 28999124 TI - The Management of Cases of "Sui" Poi Oning. PMID- 28999125 TI - Gunshot Wound of Lung and of Colon: Recovery. PMID- 28999126 TI - Case of Remittent Fever with Intestinal Ulceration. PMID- 28999128 TI - A Year's Ophthalmic and General Surgery. PMID- 28999127 TI - Small-Pox Treated by Calcium Sulphide Lotion. PMID- 28999130 TI - Current Medical Topics. PMID- 28999129 TI - A Cheerful Practice. PMID- 28999131 TI - An Elephantine Dose. PMID- 28999132 TI - The Cholera Germ. PMID- 28999133 TI - St. John Long's Liniment. PMID- 28999134 TI - Cancer of Breast: Amputation. PMID- 28999136 TI - A Cannibal Snake. PMID- 28999135 TI - The Cold-Water Treatment of Fever. PMID- 28999137 TI - Destruction of Cattle by Tigers. PMID- 28999138 TI - Opium-Smoking. PMID- 28999139 TI - Abstracts and Extracts. PMID- 28999141 TI - Some Experiments with Cholera Dejections on the Lower Animals. PMID- 28999140 TI - The Army Medical School at Netley. PMID- 28999142 TI - Outbreak of Sickness in the Thayetmyo Jail in 1881. PMID- 28999143 TI - Calcutta Medical Society. PMID- 28999144 TI - Report on Two Fatal Cases of Scorpion Sting. PMID- 28999145 TI - A Further Series of 57 Cases of Litholapaxy Performed during the Year 1883. PMID- 28999147 TI - Report of the Sanitary Commissioner with the Government of India, for 1882. PMID- 28999146 TI - Hereditary Syphilis-Gangrene of Hand and Forearm: Recovery. PMID- 28999148 TI - Urticaria. PMID- 28999150 TI - Current Medical Topics. PMID- 28999149 TI - A Case of Suppuration of an Inguinal Gland, Treated by Hypodermic Syringe. PMID- 28999151 TI - Venereal Disease in the European Army. PMID- 28999152 TI - Paralysis after Fever. PMID- 28999154 TI - Etawah Sudder Dispensary: Mal-Presentation of a Dead Foetus : Delivery by Means of Instruments. PMID- 28999153 TI - A Case of Insanity Caused by Round Worms. PMID- 28999155 TI - Acute Goitre; Its AEtiology-30 Cases Treated by the Application of Biniodide of Mercury Ointment. PMID- 28999157 TI - Vital Statistics. PMID- 28999156 TI - Chronic Diarrhoea and Dysentery in Persons Returned from Tropical to Temperate Climates. PMID- 28999159 TI - Examination of Apothecaries for Promotion. PMID- 28999158 TI - Lithotomy by Petersen's Method. PMID- 28999160 TI - Medical Societies. PMID- 28999161 TI - Jail Mortality in Bengal and the North-Western Provinces. PMID- 28999163 TI - Abstracts and Extracts. PMID- 28999164 TI - Surgical Cases: I-Compound Fracture of Leg: Amputation: Tetanus: Recovery. II Compound Fracture of Leg Involving Knee-Joint: Amputation: Re-Amputation: Recovery. PMID- 28999162 TI - The Active Principle of Indian Hemp. PMID- 28999166 TI - Abstracts and Extracts. PMID- 28999165 TI - The Uncertain Composition of Grey-Powder in India. PMID- 28999167 TI - Cholera in Bengal in 1883. PMID- 28999168 TI - A Case of Hepatic Abscess Treated by Incision and Drainage: Quick Recovery. PMID- 28999169 TI - On Sunstroke and Thermic Fever. PMID- 28999171 TI - Destruction of Cattle by Wild Animals. PMID- 28999170 TI - A Case of Phlegmasia Dolens in a Soldier. PMID- 28999172 TI - Eucalyptus Trees and Malaria. PMID- 28999173 TI - Persistence of Floral Forms. PMID- 28999174 TI - Vital Statistics. PMID- 28999175 TI - Current Medical Topics. PMID- 28999176 TI - Case of Castration Said to Be Self-Inflicted. PMID- 28999177 TI - Sarcomatous Tumour of Neck. Operation : Death : Necropsy. Remarks. PMID- 28999178 TI - Pyaemia Following Gonorrhoea : Recovery. PMID- 28999179 TI - Notes on Some Cases of Aneurism. PMID- 28999180 TI - Enteric Fever in India. PMID- 28999181 TI - Census of Indian Physicians and Surgeons. PMID- 28999182 TI - The Poison of Cholera Stools. PMID- 28999183 TI - Keratoscopy. PMID- 28999185 TI - Medical Societies. PMID- 28999184 TI - Comp. Commtd. Fracture of Tibia & Fibula: Amputation. PMID- 28999186 TI - Treatment of Dysentery. PMID- 28999187 TI - Abstracts and Extracts. PMID- 28999188 TI - Poisonous Principle in Indian Liquo-Arice Root. PMID- 28999189 TI - The Sanitation of Calcutta. PMID- 28999190 TI - OEdema Glottidis : Tracheotomy. PMID- 28999191 TI - Abrus or Jequirity Poison. PMID- 28999192 TI - Two Cases of Poisoning by Tartar Emetic. PMID- 28999194 TI - Prophylactic Use of Arsenic in Malaria. PMID- 28999193 TI - Ligature of Ulnar Artery.-Excision of Eye-Ball.-Subcoracoid Dislocation of Humerus. PMID- 28999195 TI - The Health Officership. PMID- 28999197 TI - Current Medical Topics. PMID- 28999196 TI - Radical Cure of Congenital Hydrocele. PMID- 28999198 TI - Precis of Operations Performed in Wards of the First Surgeon, Medical College Hospital, during 1883. PMID- 28999199 TI - Application of the Forceps in Breech Cases. PMID- 28999200 TI - Non-Bacillar Nature of Abrus or Jequirity Poison. PMID- 28999202 TI - Medical Societies. PMID- 28999201 TI - Abstracts and Extracts. PMID- 28999203 TI - Current Medical Topics. PMID- 28999204 TI - Female Medical Scholarships in Bengal. PMID- 28999205 TI - Buboes Treated by Aspiration. PMID- 28999206 TI - Revaccination. PMID- 28999208 TI - Calcutta Medical Society. PMID- 28999207 TI - Amputation of Thigh for Syphilitic Disease in a Patient Far Advanced in Phthisis. PMID- 28999209 TI - An Outbreak of Cholera Amongst Assam Emigrants. PMID- 28999210 TI - Is Quarantine Effective in Cholera? PMID- 28999211 TI - Cancer of the Stomach : Adhesion and Subsequent Softening : Disintegration and Perforation of the Gastric and Abdominal Walls, Allowing Free Escape of Food, &c., through the Opening of the Wound. PMID- 28999212 TI - Ophthalmic Cases: Atrophy of the Optic Nerve Following Severe Pain, of a Neuralgic Nature, in the Brow. PMID- 28999213 TI - Note on Sympathetic Ophthalmitis. PMID- 28999214 TI - A Case of Shoulder Amputation for Spreading Traumatic Gangrene. PMID- 28999215 TI - Cases. PMID- 28999216 TI - On Cholera as a Form of Uraemia. PMID- 28999218 TI - Muriate of Quinine. PMID- 28999217 TI - Current Medical Topics. PMID- 28999219 TI - Notes on Necrosis of the Femur after Gunshot Injury. PMID- 28999221 TI - 1883. PMID- 28999220 TI - Clinical Lecture on Two Cases of Amputation of the Shoulder and Hip for Sarcoma: Delivered at the Medical College Hospital on Tuesday, 11th December, 1883. PMID- 28999223 TI - Soory Charitable Dispensary-A Case of Haematoma or Bloody Cyst in the Left Axillary Region, Treated by Free Incision: Recovery. PMID- 28999222 TI - Incised Wound of the Eye-Ball. PMID- 28999225 TI - Current Medical Topics. PMID- 28999224 TI - Note on Malarial Fever. PMID- 28999226 TI - A Sickness and Life Assurance Association for India. PMID- 28999228 TI - A Case of Hyrophobia: Incubation 23 Months. PMID- 28999227 TI - A Case of Fracture of Patella Treated by Metallic Sutures. PMID- 28999230 TI - Perforating Ulcer of the Duodenum : Death by Haemorrhage: Post-Mortem Appearances. PMID- 28999229 TI - The Acute and Chronic Gastritis of Hot Climates. PMID- 28999231 TI - The Morality of Plants. PMID- 28999232 TI - Lewis on Koch's Cholera Bacillus. PMID- 28999233 TI - Subordinate Charge of Station Hospitals. PMID- 28999234 TI - Medical Societies. PMID- 28999236 TI - Recent Researches into Snake-Poison. PMID- 28999235 TI - A Tailed Child. PMID- 28999237 TI - Removal of a Large Elephantoid Tumour of Scrotum, Complicated with Scrotal Hernia of Right Side. PMID- 28999238 TI - Abstracts and Extracts. PMID- 28999239 TI - Vital Statistics. PMID- 28999240 TI - Tenure of Netley Professorships. PMID- 28999241 TI - Senile Gangrene : Amputation : Recovery. PMID- 28999242 TI - Bullet Wound of Brain : Death during the Sixth Week : Necropsy. PMID- 28999243 TI - Ten Cases of Abdominal Section. PMID- 28999244 TI - A Case of Catheter Fever. PMID- 28999245 TI - Six Months' Surgical Operations. PMID- 28999246 TI - Necrosis of Femur: Operation: Spontaneous Fracture: Amputation: Recovery. PMID- 28999248 TI - Abstracts and Extracts. PMID- 28999247 TI - Abscess of Testis Bursting into Tunica Vaginalis: Remarks. PMID- 28999249 TI - Ulcers of Leg Amongst Sepoys. PMID- 28999250 TI - Stone in the Bladder in Upper Assam. PMID- 28999251 TI - Cerebro-Spinal Disseminated Sclerosis in Soldiers. PMID- 28999253 TI - Pettenkofer on Virchow's Cholera Theories. PMID- 28999252 TI - Cobra Poison,-Its Chemical Nature and Physiological Action. PMID- 28999254 TI - Current Medical Topics. PMID- 28999255 TI - A Monster. PMID- 28999256 TI - The Active Principle of Indian Hemp. PMID- 28999258 TI - The Gynecologist. PMID- 28999257 TI - Excision of Tongue by Scissors by Billroth's Method. PMID- 28999259 TI - A Caution to Vaccinators. PMID- 28999260 TI - Medical News. PMID- 28999261 TI - Indian Medicinal Plants (Part II). PMID- 28999262 TI - Cases Illustrating the Use of the Elastic Ligature. PMID- 28999263 TI - Report on the Medico-Legal Returns Received from the Civil Surgeons in the Bengal Presidency during the Years 1870, 1871, and 1872. PMID- 28999264 TI - A New Disease in Madras. PMID- 28999265 TI - On Disorders of Pigmentation. PMID- 28999266 TI - The Massacre in the Naga Hills. PMID- 28999267 TI - Cases from Practice. PMID- 28999268 TI - Cases Treated in the 2nd Surgeon's Ward, Medical College Hospital. PMID- 28999269 TI - Adulteration of Milk. PMID- 28999271 TI - The Treatment of Cholera. PMID- 28999270 TI - A Case of Death from Fracture of the Skull. PMID- 28999272 TI - Notes on a Trip Home by China and America. PMID- 28999273 TI - On the Nature and Physiological Action of the Poison of Naja Tripudians and Other Indian Venomous Snakes. PMID- 28999274 TI - Periosteal Abscess of Thigh Extending to Knee-Joint: Aspiration: Incision: Recovery. PMID- 28999276 TI - Cholera in 1873. PMID- 28999275 TI - Cholera in Gurgaon. PMID- 28999277 TI - Extension of the University of Edinburgh. PMID- 28999278 TI - The Etiology of Madura Foot. PMID- 28999280 TI - Cholera. PMID- 28999279 TI - Some Notes on Skin Grafting. PMID- 28999281 TI - Lewis on Nematode Haematozoa. PMID- 28999282 TI - Report on the Medico-Legal Returns Received from the Civil Surgeons in the Bengal Presidency during the Years 1870, 1871, and 1872. PMID- 28999283 TI - Medical and Sanitary Report of the Native Army of Bengal for the Year 1873. PMID- 28999284 TI - The Medical Aspect of Short Leave to Europe. PMID- 28999285 TI - Cases from Practice. PMID- 28999286 TI - Indian Medicinal Plants. PMID- 28999288 TI - Typhoid Fever in Meean Meer. PMID- 28999287 TI - A Case of Tetanus Successfully Treated. PMID- 28999290 TI - Medical News. PMID- 28999289 TI - Observations on the Treatment of Ulcers in the Convict Hospital at Haddo, in Medical Charge of Surgeon J. Reid, M. B., 2nd Medical Officer, Port Blair. PMID- 28999291 TI - The Late Deputy Surgeon General H. B. Buckle, C.B. PMID- 28999293 TI - Idiopathic Tetanus Treated with Chloral Hydrate; Recovery. PMID- 28999292 TI - On the Nature and Physiological Action of the Poison of Naja Tripudians and Other Indian Venomous Snakes. PMID- 28999294 TI - Notes with Observations on a Case of Enteric Fever in a Native. PMID- 28999296 TI - Case of Obstruction of the Bowels Treated by Means of Strychnine. PMID- 28999295 TI - A Case of Lithotomy. PMID- 28999297 TI - Medical News. PMID- 28999298 TI - Medical and Sanitary Report of the Native Army of Bengal for the Year 1873. PMID- 28999299 TI - 1874. PMID- 28999301 TI - Report on the Medico-Legal Returns Received from the Civil Surgeons in the Bengal Presidency during the Years 1870, 1871, and 1872. PMID- 28999300 TI - Phimosis and Circumcision. PMID- 28999302 TI - Case of Poisoning by the Mylabris Cichorii (Telini Fly). PMID- 28999303 TI - On the Nature and Physiological Action of the Poison of Naja Tripudians and Other Indian Venomous Snakes. PMID- 28999304 TI - A Case of Death by Maggots. PMID- 28999306 TI - The Late Sir James Ranald Martin, C. B. PMID- 28999305 TI - Observations on Leprosy and on Its Treatment by Means of Vaporized Carbolic Acid in Union with Watery Vapor. PMID- 28999307 TI - The Medical Retiring Fund. PMID- 28999308 TI - Honoris Causa. PMID- 28999309 TI - On the Bloodless Removal of Elephantoid Tumours of the Scrotum. PMID- 28999310 TI - Observations upon Some Severe Injuries of the Skull and Brain. PMID- 28999311 TI - Case of Haematocele of the Spermatic Cord. PMID- 28999312 TI - A Sanitarium for Tonghoo. PMID- 28999313 TI - Case of Empyema. PMID- 28999314 TI - Report on the Medico-Legal Returns Received from the Civil Surgeons in the Bengal Presidency during the Years 1870, 1871, and 1872. PMID- 28999315 TI - Overwork. PMID- 28999316 TI - Notes on Cases of Pneumonia on the N W. Provinces. PMID- 28999317 TI - Treatment of Heat Apoplexy or Sunstroke. PMID- 28999318 TI - The Calcutta Medical College. PMID- 28999319 TI - Reports. PMID- 28999320 TI - Conveyance of Contagion by Flies. PMID- 28999321 TI - Two Cases of Poisoning by Opium Successfully Treated by Subcutaneous Injection of Atropine. PMID- 28999322 TI - Wanted.-A Diagnosis. PMID- 28999324 TI - Abscess of the Liver. PMID- 28999323 TI - On Disorders of Pigmentation. PMID- 28999325 TI - A Successful Case of Lithotomy. PMID- 28999327 TI - Medical News. PMID- 28999326 TI - On the Nature and Physiological Action of the Poison of Naja Tripudians and Other Indian Venomous Snakes. PMID- 28999329 TI - Operation for Fistula in Ano. PMID- 28999328 TI - Exchange into the British Medical Department. PMID- 28999330 TI - Sir John Campbell Brown, K.C.B. PMID- 28999331 TI - A Case of Asphyxia Followed by Tracheotomy. PMID- 28999332 TI - Notes from the United States and Canada. PMID- 28999333 TI - Medical Superstitions in Rajputana. PMID- 28999334 TI - Report on the Medico-Legal Returns Received from the Civil Surgeons in the Bengal Presidency during the Years 1870, 1871, and 1872. PMID- 28999335 TI - Intravenous Injection of Choleraic and Other Organic Fluids. PMID- 28999337 TI - Sulphur Fumigations in Cholera. PMID- 28999336 TI - Cases Treated in the 2nd Surgeon's Wards. PMID- 28999339 TI - Enteric Fever in the 85th Regiment. PMID- 28999338 TI - On the Nature and Physiological Action of the Poison of Naja Tripudians and Other Indian Venomous Snakes. PMID- 28999340 TI - On the Treatment of Cholera by Sub-Cutaneous Injection of Water. PMID- 28999341 TI - On the Treatment of Heat Apoplexy. PMID- 28999342 TI - Assistant Surgeons' Grievances. PMID- 28999343 TI - Experiences of an Assistant Surgeon, Principally Medico-Legal. PMID- 28999345 TI - Cases from Practice. PMID- 28999344 TI - Malformations of the Hands and Feet. PMID- 28999346 TI - Medical News. PMID- 28999347 TI - On Disorders of Pigmentation. PMID- 28999348 TI - An Inquiry into Leprosy. PMID- 28999350 TI - Cardiac Polypus in Connection with Malaria. PMID- 28999349 TI - A Medico-Legal Case. PMID- 28999351 TI - Insane Delusions. PMID- 28999352 TI - Report on the Medico-Legal Returns Received from the Civil Surgeons in the Bengal Presidency during the Years 1870, 1871, and 1872. PMID- 28999353 TI - Case of Scrotal Tumour; Operation; Repeated Secondary Haemorrhage; Diabetes: Recovery. PMID- 28999355 TI - The Punjab Medical Missionary Society. PMID- 28999354 TI - Notes of Surgical Cases at the Kooshteah Dispensary. PMID- 28999357 TI - Departmental Examinations. PMID- 28999356 TI - Medical News. PMID- 28999358 TI - Vaccination in Bengal. PMID- 28999359 TI - Cholera. PMID- 28999360 TI - Report on an Outbreak of Small-Pox in the Darjeeling District. PMID- 28999362 TI - On the Nature and Physiological Action of the Poison of Naja Tripudians and Other Indian Venomous Snakes. PMID- 28999361 TI - Curry-Eaters Beware! PMID- 28999363 TI - Notes of Surgical Cases under Treatment at the Goalundo Dispensary. PMID- 28999365 TI - On Disorders of Pigmentation. PMID- 28999364 TI - The Indian Medical Service and Dr. Fayrer. PMID- 28999367 TI - Notes on Cases of Pneumonia on the N. W. Frontier. PMID- 28999366 TI - Soldiers' Wives and Children. PMID- 28999368 TI - Free Sulphurous Acid as a Prophylactic against Cholera. PMID- 28999370 TI - The Disposal of the Dead. PMID- 28999369 TI - Bengal Lunatic Asylum. PMID- 28999371 TI - Cases from Practice. PMID- 28999372 TI - Report of the Medico-Legal Returns Received from the Civil Surgeons in the Bengal Presidency, during the Years 1870, 1871, and 1872. PMID- 28999373 TI - Medical News. PMID- 28999374 TI - Aphasia with Hemiplegia of the Right Side; the Result of Injury to the Left Hemisphere. PMID- 28999375 TI - The Carbazotate of Ammonia. PMID- 28999376 TI - Case of Salivary Fistula. PMID- 28999378 TI - Medical Notes from the City of the Saints. PMID- 28999377 TI - Report of an Enquiry into the Conditions during Life of the Liver and Kidneys in Asiatic Cholera, with Especial Reference to the Management of the Stage of Collapse, and to the Prevention and Treatment of the Cholo-Uraemic Complication of the Reaction Stage of Cholera. PMID- 28999379 TI - Droppings of Birds a Cause of Cholera. PMID- 28999380 TI - A Case of Sporadic Cholera. PMID- 28999381 TI - Cases from Practice. PMID- 28999383 TI - On Disorders of Pigmentation. PMID- 28999382 TI - Surgery in the Malarious District of Jehanabad. PMID- 28999384 TI - The Microscopic Appearances of the Blood in Cholera. PMID- 28999385 TI - Cases from Practice. PMID- 28999386 TI - On the Nature and Physiological Action of the Poison of Naja Tripudians and Other Indian Venomous Snakes. PMID- 28999388 TI - Medical Fees. PMID- 28999387 TI - A Case of Traumatic Tetanus Treated with Chloral Hydrate and Potassii Bromid. Recovery. PMID- 28999390 TI - Medical News. PMID- 28999389 TI - The Burdwan Fever. PMID- 28999391 TI - Disinfectant Treatment of Cholera. PMID- 28999392 TI - Hypodermic Injection of Chloral Hydrate in Two Cases of Colapsed Stage of Cholera: Recovery. PMID- 28999393 TI - Medical Fees. PMID- 28999395 TI - Cholera in the Burdwan Jail; Sudden Outbreak; Sudden Cessation after Fumigation with Sulphurous Acid. PMID- 28999394 TI - Report on the Medico-Legal Returns, Received from the Civil Surgeons in the Bengal Presidency during the Years 1870, 1871, and 1872. PMID- 28999397 TI - The Medical Fee Question in Madras. PMID- 28999396 TI - Gunshot Fracture of the Femur: Recovery, without Amputation. PMID- 28999398 TI - On the Phytodermata or Parasitic Diseases of the Skin (Tineae) of Vegetable Origin. PMID- 28999400 TI - State of the Pericardium in Hanging. PMID- 28999399 TI - Report of an Outbreak of Cholera in the Thomason Civil Engineering College, Roorkee. PMID- 28999401 TI - Cholera in Simla. PMID- 28999403 TI - Report on the Malwa Charitable Dispensaries for the Year 1874. PMID- 28999402 TI - A Suggestion for the Prevention of Osteo-Myelitis. PMID- 28999405 TI - Cholera in Simla. PMID- 28999404 TI - Erysipelas in Calcutta. PMID- 28999406 TI - Report on the Medico-Legal Returns, Received from the Civil Surgeons in the Bengal Presidency during the Years 1870, 1871, and 1872. PMID- 28999407 TI - Blood-Letting. PMID- 28999408 TI - Case of Diabetes Mellitus or Glycohaemia. PMID- 28999409 TI - Extraction of a Pea from the Ear by the Aid of Chloroform. PMID- 28999411 TI - Chloride of Ammonium in Hepatic Abscess. PMID- 28999410 TI - Incessant Hiccup. PMID- 28999412 TI - The Burdwan Fever. PMID- 28999413 TI - Cases from Practice. PMID- 28999414 TI - Disinfectant Treatment of Cholera. PMID- 28999416 TI - A Diagnosis. PMID- 28999415 TI - On the Phytodermata or Parasitic Diseases of the Skin (Tineae) of Vegetable Origin. PMID- 28999417 TI - Report of an Outbreak of Cholera in the Thomason Civil Engineering College, Roorkee. PMID- 28999419 TI - Medical News. PMID- 28999418 TI - Medical Missions. PMID- 28999421 TI - Cases Treated in the 1st Surgeon's Wards. PMID- 28999420 TI - Case of Strangulated Scrotal Hernia: Reduction by Inversion. PMID- 28999422 TI - Dhatura Poisoning. PMID- 28999423 TI - Quacks and Quackery. PMID- 28999424 TI - The Treatment of Snake-Poisoning in Australia. PMID- 28999425 TI - Sulphur Fumigation in Cholera. PMID- 28999426 TI - Malformations of the Hands and Feet. PMID- 28999428 TI - Dr. Fayrer at Netley. PMID- 28999429 TI - Indian Medicinal Plants: Part III. PMID- 28999427 TI - Notes on Liver Abscess. PMID- 28999431 TI - Report on the Medico-Legal Returns Received from the Civil Surgeons in the Bengal Presidency during the Years 1870, 1871, and 1872. PMID- 28999430 TI - Treatment of Heat Apoplexy, or Sunstroke. PMID- 28999432 TI - On Disorders of Pigmentation. PMID- 28999434 TI - Medical News. PMID- 28999433 TI - The Treatment of Chronic Dysentery. PMID- 28999436 TI - A Case of Spina Bifida Successfully Treated by Puncture and Injection. PMID- 28999435 TI - The Place for the Surgeon-General, Indian Medical Department. PMID- 28999437 TI - Overwork. PMID- 28999438 TI - Dr. Moore's Manual of Family Medicine. PMID- 28999439 TI - Injury of the Head; Abcess; Brain Symptoms: Death. PMID- 28999440 TI - Errata. AB - [This corrects the article on p. 124 in vol. 10.]. PMID- 28999441 TI - Simla. PMID- 28999442 TI - Precedence. PMID- 28999443 TI - Report of an Outbreak of Cholera in the Thomason Civil Engineering College, Roorkee. PMID- 28999444 TI - Report on the Medico-Legal Returns Received from the Civil Surgeons in the Bengal Presidency during the Years 1870, 1871, and 1872. PMID- 28999446 TI - Cinchona Cultivation in Darjeeling. PMID- 28999445 TI - A Case Illustrating the State of the Pericardium after Death by Hanging. PMID- 28999447 TI - The Election of Tagore Law Professor. PMID- 28999448 TI - The Aboo Lawrence School. PMID- 28999449 TI - On the Nature and Physiological Action of the Poison of Naja Tripudians and Other Indian Venomous Snakes. PMID- 28999450 TI - On Disorders of Pigmentation. PMID- 28999451 TI - Irritant Causes of Disease-Pneumonia. PMID- 28999452 TI - Medical News. PMID- 28999453 TI - Case of Hepatic Abscess Treated by the Aspirator. PMID- 28999454 TI - Disinfectant Treatment of Cholera. PMID- 28999455 TI - Amputation of the Forearm; Osteomyelitis and Pyaemia: Recovery. PMID- 28999456 TI - Case of Human Sacrifice, Suicidal or Murderous. PMID- 28999457 TI - Conversion of Nerve Force into Heat. PMID- 28999460 TI - Cholera. PMID- 28999459 TI - Properties of Jaborandi. PMID- 28999458 TI - Case of Calculus in the Female Bladder. PMID- 28999462 TI - Female Medical Education in Madras. PMID- 28999463 TI - Medical Education in Burmah. PMID- 28999461 TI - Leprosy in Norway. PMID- 28999464 TI - Nattore Dispensary. PMID- 28999465 TI - Case of Cholera Treated by Sulphurous Acid. PMID- 28999467 TI - On the Nature and Physiological Action of the Poison of Naja Tripudians and Other Indian Venomous Snakes. PMID- 28999466 TI - Medical News. PMID- 28999468 TI - Case of Twins: Transverse Presentation: Turning. PMID- 28999469 TI - The Female Medical School at Bareilly. PMID- 28999470 TI - Report on the Medico-Legal Returns Received from the Civil Surgeons in the Bengal Presidency during the Years 1870, 1871, and 1872. PMID- 28999471 TI - Jehanabad Dispensary. PMID- 28999472 TI - Indian Medicinal Plants. PMID- 28999473 TI - On the Phytodermata or Parasitic Disease of the Skin (Tineoe) of Vegetable Origin. PMID- 28999474 TI - Cholera. PMID- 28999475 TI - Cases of Penetrating Abdominal Wound- Purulia Dispensary. PMID- 28999476 TI - Chuckdighee Dispensary. PMID- 28999478 TI - Kishnaghur Dispensary. PMID- 28999477 TI - Report of an Outbreak of Cholera in the Thomason Civil Engineering College, Roorkee. PMID- 28999479 TI - On the Treatment of Ringworm and Other Forms of Skin Disease by Boracic Acid. PMID- 28999480 TI - Maldah Dispensary. PMID- 28999481 TI - Fireflies. PMID- 28999482 TI - Ferruginous Preparations in Specific Cholera. PMID- 28999483 TI - Leper Burial. PMID- 28999484 TI - Pooteah Dispensary. PMID- 28999485 TI - Irritant Causes of Disease-Pneumonia. PMID- 28999486 TI - Extract from Dr. Koch's Report on Cholera in Egypt. PMID- 28999488 TI - Current Medical Topics. PMID- 28999487 TI - Penetrating Wound of the Abdomen: Recovery. PMID- 28999489 TI - Current Medical Topics. PMID- 28999490 TI - Reasoning by Analogy. PMID- 28999491 TI - Alterations in the Red Blood-Corpuscles from the Action of Malaria. PMID- 28999492 TI - Service Notes. PMID- 28999493 TI - On the Instruments Required in the Operation of Litholapaxy. PMID- 28999494 TI - General Hospital: Two Cases of Acute Rheumatism. PMID- 28999496 TI - Appointments, Leave, Promotions, and Retirements. PMID- 28999495 TI - 1885. PMID- 28999497 TI - Medical News. PMID- 28999498 TI - A Severe Case of Irritation of the Superior Maxillary Nerve and Its Connections, Caused by the Roots of a Diseased Molar. PMID- 28999499 TI - Burrisal Dispensary: Case of Puerperal Eclampsia, Contracted Pelvis, Prolapse of the Cord; Craniotomy. PMID- 28999501 TI - Can Flies Carry Cholera? PMID- 28999500 TI - Vital Statistics and Sanitary Notes. PMID- 28999502 TI - Medical News. PMID- 28999503 TI - Service Notes. PMID- 28999504 TI - Extract. PMID- 28999505 TI - Acute Pneumonia in Famine. PMID- 28999506 TI - Current Medical Topics. PMID- 28999507 TI - On Aconite in the Treatment of Pneumonia. PMID- 28999508 TI - Amritsar Civil Hospital: Laryngeal Fistula-Amputation of Leg-Sarcoma-Epithilial Cancer-Cystic Tumour. PMID- 28999510 TI - Vital Statistics and Sanitary Notes. PMID- 28999509 TI - A Peculiar Form of Whooping Cough. PMID- 28999511 TI - Brief Notes on the So-Called 'Panjdeh sore'. PMID- 28999512 TI - On Some Pathologico-Pigmentary Changes Seen in Remittent Fever. PMID- 28999513 TI - Calcutta Police Hospital: Syphilitic Paraplegia-Pleuro-Pneumonia. PMID- 28999514 TI - The Calcutta L. M. S. PMID- 28999515 TI - Cause of Hepatic Abscess. PMID- 28999516 TI - Syncope of Heart in Acute Gastro-Intestinal Disorders. PMID- 28999517 TI - Transactions of Medical Societies. PMID- 28999518 TI - Bengal Jails. PMID- 28999520 TI - Appointments, Leave, &c. PMID- 28999519 TI - Fever. PMID- 28999521 TI - Case of Laceration of Perineum and Scrotum. PMID- 28999522 TI - Transmission of Yellow Fever by the Mosquito. Hydrofluoric Inhalations in Phthisis. PMID- 28999523 TI - Medical News. PMID- 28999524 TI - Current Medical Topics. PMID- 28999525 TI - Transactions of Medical Societies. PMID- 28999526 TI - District Jail Hospital, Bilaspur: Case of Obscure Peritonitis. PMID- 28999527 TI - Intubation of the Larynx. PMID- 28999528 TI - Extracts. PMID- 28999530 TI - Brain Surgery. PMID- 28999529 TI - Contributions to the Indian Materia Medica. PMID- 28999531 TI - Memorandum on Fusel Oil. PMID- 28999532 TI - Appointments, Leave, &c. PMID- 28999533 TI - A Case of Unnatural Labor. PMID- 28999535 TI - Dr. Harley on Hepatic Abscess. PMID- 28999534 TI - On the Treatment of Ophthalmia. PMID- 28999537 TI - Medical News. PMID- 28999536 TI - Pathology of Remittent Fever. PMID- 28999538 TI - Vital Statistics & Sanitary Notes. PMID- 28999539 TI - Some Remarks on the Specific Origin of Disease. PMID- 28999541 TI - Appointments, Leave, &c. PMID- 28999540 TI - Pepsine in the Treatment of Chronic Tropical Diarrhoea. PMID- 28999542 TI - Case of Snake-Poisoning. PMID- 28999544 TI - Native Treatment of Retained Placenta. PMID- 28999543 TI - Case of Death from Rupture of the Liver, &c. PMID- 28999546 TI - Epidemic or Endemic. PMID- 28999545 TI - Current Medical Topics. PMID- 28999547 TI - Transactions of Medical Societies. PMID- 28999548 TI - Precis of Operations Performed in the Indore Charitable Dispensary. PMID- 28999549 TI - Notes of a Case of Cerebro-Spinal Fever, with Autopsy. PMID- 28999550 TI - Cholera in Calcutta. PMID- 28999551 TI - Examination for the Indian Medical Service. PMID- 28999553 TI - Service Notes. PMID- 28999552 TI - Note on Pasteur's Treatment. PMID- 28999554 TI - Acute Pneumonia in Famine. PMID- 28999556 TI - The Advantages and Disadvantages of Human and Animal Lymph. PMID- 28999555 TI - On the Therapeutic Value of Tinctura Cannabis Indica in the Treatment of Dysentery. PMID- 28999557 TI - Kala-Azar. PMID- 28999558 TI - The Treatment of Toothache. PMID- 28999559 TI - Amritsar Civil Hospital: Idiopathic Tetanus-Obstruction of Bowels. PMID- 28999560 TI - Appointments, Leave, &c. PMID- 28999561 TI - Bhawalpore State Sadar Hospital: Notes on the Surgical Treatment of a Huge Liver Abscess. PMID- 28999562 TI - The Operation of Litholapaxy. PMID- 28999563 TI - Two More Cases of Stone in a Prolapsed Bladder. PMID- 28999564 TI - Vital Statistics and Sanitary Notes. PMID- 28999565 TI - Emphysema of Right Cheek and Side of Neck after Dislocation of Nasal Cartilage. PMID- 28999566 TI - The Twenty-First Annual Report of the Sanitary Commissioner with the Government of India. PMID- 28999567 TI - Unconscious Memory in Disease. PMID- 28999568 TI - Service Notes. PMID- 28999569 TI - Calcutta Medical College Hospital: Case of Fracture of Skull, Exploration of Wound, Death. PMID- 28999570 TI - The Thermometer in Epilepsy. PMID- 28999571 TI - A New Source of Danger in Wounds of the Throat and Neck. PMID- 28999572 TI - The Calcutta Medical Society. PMID- 28999574 TI - Current Medical Topics. PMID- 28999573 TI - Notes on the Prevention and Treatment of Scurvy in Peace and War. PMID- 28999575 TI - Medical News. PMID- 28999576 TI - Vital Statistics and Sanitary Notes. PMID- 28999577 TI - Service Notes. PMID- 28999578 TI - Regimental Hospital, 23rd Bo. L. I. Case of Mercurialism. PMID- 28999579 TI - Appointments, Leave, &c. PMID- 28999580 TI - Sadar Dispensary, Dharmsala: Removal of an Enormous Fibro-Cellular Tumor of 15 Years' Standing. PMID- 28999582 TI - Medical News. PMID- 28999581 TI - A Case of Suicidal Hanging. PMID- 28999583 TI - Enteric Fever in the European Army of India in 1884. PMID- 28999584 TI - Official Science. PMID- 28999585 TI - Prevalence of Goitre in Chiniot, and in the Villages about It. PMID- 28999586 TI - New Mode of Applying Cocaine. PMID- 28999587 TI - Case of Impacted Urethral Calculus. PMID- 28999588 TI - Current Medical Topics. PMID- 28999589 TI - Improved Lithotrites. PMID- 28999590 TI - Transactions of Medical Societies. PMID- 28999591 TI - Presidency General Hospital: Cases of Miliary Fever. PMID- 28999592 TI - Note on the Meteorological Phenomena Accompanying an Outbreak of Cholera in Agra. PMID- 28999593 TI - Notes on the Prevention and Treatment of Scurvy in Peace and War. PMID- 28999594 TI - The Treatment of Wounds. PMID- 28999595 TI - Transactions of Medical Societies. PMID- 28999596 TI - Epileptic Insanity. PMID- 28999597 TI - Medical News. PMID- 28999598 TI - On Antiseptic Surgery and Its Application in Military Hospitals and in the Field. PMID- 28999599 TI - Cholera in Relation to Water-Supply in Southern India. PMID- 28999600 TI - Current Medical Topics. PMID- 28999601 TI - Indore Charitable Dispensary: A Second Case of Hydrophobia Treated by the Topical Application of Muriate of Cocaine. PMID- 28999602 TI - Appointments, &c. PMID- 28999603 TI - Pass Lists of British and Indian Medical Services. PMID- 28999604 TI - Service Notes. PMID- 28999606 TI - Haddo Hospital, Port Blair: A Case of Traumatic Tetanus Ending in Recovery. PMID- 28999605 TI - Cocaine and Cataract. PMID- 28999607 TI - Army Medical School, Netley. PMID- 28999608 TI - Spaying. PMID- 28999609 TI - Vaccination. PMID- 28999610 TI - Fever. PMID- 28999611 TI - Vital Statistics and Sanitary Notes. PMID- 28999612 TI - Transactions of Medical Societies. PMID- 28999614 TI - Surgeon-General Cowie on Cerbro-Spinal Fever in Calcutta. PMID- 28999613 TI - Prevention of Scurvy in Peace and War. PMID- 28999615 TI - Gunshot Wound of Heart. Patient Survived 42 Hours after Injury. PMID- 28999617 TI - Current Medical Topics. PMID- 28999616 TI - The University of Calcutta. PMID- 28999618 TI - Appointments, Leave, &c. PMID- 28999619 TI - The Action of Reagents on Cobra-Poison. PMID- 28999621 TI - Cerebro-Spinal Fever. PMID- 28999620 TI - Begooserai Charitable Dispensary-Case of Omental Protrusion. PMID- 28999623 TI - Service Notes. PMID- 28999622 TI - Civil Hospital, Amritsar, Punjab: Glandular Tumour of Neck-Extravasation of Urine Cock's Operation-Large Tumour of Breast-Rhinoplasty. PMID- 28999624 TI - On Antiseptic Surgery and Its Application in Military Hospitals and in the Field. PMID- 28999625 TI - Medical News. PMID- 28999626 TI - Vital Statistics and Sanitary Notes. PMID- 28999627 TI - Service Notes. PMID- 28999628 TI - On Antiseptic Surgery: And Its Application in Military Hospitals and in the Field. PMID- 28999629 TI - Litholapaxy in Male Children and Male Adults. PMID- 28999630 TI - Pubna Charitable Dispensary. Cases from Hospital Practice. PMID- 28999631 TI - The Value of Chrysophanic Acid as a Remedy in Skin Disease. PMID- 28999633 TI - Equine Relapsing Fever. PMID- 28999632 TI - Appointments, &c. PMID- 28999634 TI - A Case of Protracted Labor. PMID- 28999635 TI - Current Medical Topics. PMID- 28999636 TI - Transactions of Medical Societies. PMID- 28999637 TI - Medical News. PMID- 28999638 TI - Dropsy in Famine. PMID- 28999639 TI - Dumraon Raj Hospital: A Case of Partial Resection of the Elbow Joint for Compound Dislocation, with Laceration of the Brachial Artery at the Bend of the Elbow. PMID- 28999640 TI - A Case of Unnatural Labour. PMID- 28999641 TI - On the Occurrence of Icterus, Icteric Urine, and Haematinuria in Remittent Fever. PMID- 28999642 TI - Transactions of Medical Societies. PMID- 28999644 TI - Vital Statistics and Sanitary Notes. PMID- 28999643 TI - A Case of Puerperal Convulsions. Treated with Chloroform Inhalation. PMID- 28999645 TI - Malarial Scurvy and the Post-Molar Ulcer. PMID- 28999647 TI - Appointments, Retirements, &c. PMID- 28999646 TI - On the Use of Cocaine in the Treatment of Gonorrhoeal Ophthalmia. PMID- 28999648 TI - Current Medical Topics. PMID- 28999649 TI - The Malarial Germ. PMID- 28999650 TI - Notes on the Rabic Virus. PMID- 28999651 TI - On Antiseptic Surgery and Its Application in Military Hospitals and in the Field. PMID- 28999652 TI - The Position and Pay of Brigade-Surgeons in India. PMID- 28999653 TI - Service Notes. PMID- 28999654 TI - Notes on a Series of 100 Cases of Lithotomy Performed at the Bhuj Civil Hospital. PMID- 28999655 TI - The Cause of Rupture of Spleen. PMID- 28999656 TI - Dropsy in Famine. PMID- 28999658 TI - Nursing in Indian Military Hospitals. PMID- 28999657 TI - Antipyrin: Its Value in Pyrexia. PMID- 28999660 TI - Transactions of Medical Societies. PMID- 28999659 TI - Opium Dyscrasia. PMID- 28999661 TI - Syphilis and Marriage. PMID- 28999662 TI - Medical News. PMID- 28999663 TI - Appointments, Furlough, Leave, &c. PMID- 28999664 TI - Pubna Charitable Dispensary: Tumour of Vulva-Ranula-Enchondroma-Amputation of Leg. PMID- 28999665 TI - Service Notes. PMID- 28999667 TI - Pettenkofer on Cholera. PMID- 28999666 TI - The Treatment of Diabetes with Pepsine. PMID- 28999668 TI - Vital Statistics and Sanitary Notes. PMID- 28999669 TI - Current Medical Topics. PMID- 28999670 TI - Spina Bifida Cured by Structure of Iodine and Glycerine. PMID- 28999671 TI - Civil and Presidency Surgeon. PMID- 28999672 TI - Burrisal Charitable Dispensary: Case of Compound Fracture of the Skull. PMID- 28999673 TI - Clinical Notes on Mycetoma. PMID- 28999674 TI - Appointments, Leave, &c. PMID- 28999675 TI - The Influence of Sewerage and Water-Supply on Public Health. PMID- 28999676 TI - Transactions of Medical Societies. PMID- 28999678 TI - Service Notes. PMID- 28999677 TI - Fever in the Madras Famine. PMID- 28999679 TI - Current Medical Topics. PMID- 28999680 TI - Bengal Jails. PMID- 28999681 TI - Cases of Gun-Shot Injuries Which Occurred at Shwebo, Upper Burma. PMID- 28999682 TI - Cause of Hepatic Abscess. PMID- 28999684 TI - Medical News. PMID- 28999683 TI - Scurvy. PMID- 28999686 TI - Vital Statistics and Sanitary Notes. PMID- 28999685 TI - A Word of Advice to Young Indian Medical Graduates. PMID- 28999687 TI - Service Notes. PMID- 28999688 TI - Vital Statistics and Sanitary Notes. PMID- 28999689 TI - Calcutta Medical Society. PMID- 28999691 TI - Medical News. PMID- 28999690 TI - Scurvy. PMID- 28999692 TI - Rectal Injection of Gases in Diseases of the Lungs. PMID- 28999693 TI - Service Notes. PMID- 28999694 TI - Current Medical Topics. PMID- 28999695 TI - Cases of Litholapaxy Performed on Children. PMID- 28999696 TI - Transactions of Medical Societies. PMID- 28999697 TI - Civil Hospital, Bareilly: A Brief Description of Four Interesting Cases. PMID- 28999698 TI - Report of a Localized Outbreak of Cholera Due Apparently to Contaminated Water and Milk. PMID- 28999699 TI - Appointments, Leave, &c. PMID- 28999701 TI - Uniform of Surgeons. PMID- 28999700 TI - Medical Education and Relief in Hyderabad. PMID- 28999702 TI - Purulia Dispensary, Manbhoom: Clinical Notes on Some Surgical Cases. PMID- 28999704 TI - Dr. Richards on Pasteurism. PMID- 28999703 TI - Cases of Litholapaxy in Male Children. PMID- 28999705 TI - Precis of Operations Performed in the Wards of the 1st Surgeon, Medical College Hospital. PMID- 28999706 TI - Litholapaxy in Male Children. PMID- 28999708 TI - New Cure for Consumption. PMID- 28999707 TI - Medical News. PMID- 28999709 TI - Operations Performed in the Afzul Gunj Hospital. PMID- 28999710 TI - Service Notes. PMID- 28999711 TI - The Mayo Memorial Hospital. PMID- 28999712 TI - Transactions of Medical Societies. PMID- 28999713 TI - Appointments, Leave, &c. PMID- 28999714 TI - Scirrhus Recti in India-The Liability of Mistaking Chronic Dysentery for This Disease. PMID- 28999716 TI - Pasteurism. PMID- 28999715 TI - Phthisis in Famine. PMID- 28999717 TI - Vital Statistics and Sanitary Notes. PMID- 28999718 TI - New Investigations on Cholera. PMID- 28999719 TI - On Some Forms of Albuminuria Not Dangerous to Life. PMID- 28999720 TI - The Effects of an Overdose of Cocaine. PMID- 28999722 TI - The Products of Bacteria. PMID- 28999721 TI - Diagram of the Medical Corps of an English Army in the Field. PMID- 28999723 TI - Medical News. PMID- 28999724 TI - Women and Medicine. PMID- 28999725 TI - Current Medical Topics. PMID- 28999726 TI - Umballa Civil Hospital: A Case of Retention of Urine. PMID- 28999727 TI - Service Notes. PMID- 28999728 TI - The Educational Function of the Indian Medical Service. PMID- 28999729 TI - An Indian Degree in Sanitary Science. PMID- 28999731 TI - Appointments, Leave, &c. PMID- 28999730 TI - Transactions of Medical Societies. PMID- 28999733 TI - Medical News. PMID- 28999732 TI - The Calcutta L.M.S. PMID- 28999735 TI - 1886. PMID- 28999734 TI - Contributions to the Indian Materia Medica: On the Medical Properties of Some of the Indigenous Plants of Southern India. PMID- 28999736 TI - Current Medical Topics. PMID- 28999738 TI - Note on the Connection between Papillitis and Chronic Cerebral Disease. PMID- 28999737 TI - A Case of Transverse Presentation, with Prolapse of Both Arms and Cord, and Its Successful Delivery. PMID- 28999739 TI - The Countess of Dufferin's Fund. PMID- 28999741 TI - Fazilka Dispensary: A Case of Imperforate Anus. PMID- 28999743 TI - Extracts. PMID- 28999740 TI - On the Relative Digestive Value of Fairchild's Peptonising Powders, Pepsine, and Papaya Juice on Milk. PMID- 28999742 TI - Vital Statistics & Sanitary Notes. PMID- 28999745 TI - Appointments, Leave, &c. PMID- 28999744 TI - Borax in Enlargement of the Spleen. PMID- 28999746 TI - Vital Statistics and Sanitary Notes. PMID- 28999747 TI - Extract. PMID- 28999749 TI - The Treatment of Toothache. PMID- 28999748 TI - Erratum. AB - [This corrects the article on p. 90 in vol. 22.]. PMID- 28999750 TI - Current Medical Topics. PMID- 28999751 TI - Civil Hospital Amritsur: Cases of Operations Performed. PMID- 28999753 TI - Fasting. PMID- 28999752 TI - The Health of the European Army of India in 1885. PMID- 28999754 TI - Some Notes on the Interior Economy of Army Hospitals in India. PMID- 28999755 TI - The Sister Medical Services. PMID- 28999756 TI - A Case of Hydrophobia. PMID- 28999758 TI - Venereal Disease in the European Army. PMID- 28999757 TI - Notes on an Epidemic of Pneumonitis. PMID- 28999760 TI - Mortality of Bengal Jails. PMID- 28999759 TI - On Puncturing the Liver's Capsule as a Remedial Measure in Case of Chronic Congestive Hypertrophy. PMID- 28999762 TI - Medical News. PMID- 28999761 TI - Service Notes. PMID- 28999763 TI - Precis of Operations Performed in the Wards of the First Surgeon, Medical College Hospital: During the Year 1886. PMID- 28999764 TI - A Case of Transverse Presentation with Prolapse of Right Arm and Hand, and Successful Delivery of a Living Child. PMID- 28999765 TI - Transactions of Medical Societies. PMID- 28999766 TI - Pasteurism. PMID- 28999767 TI - Remarks on the Mode of Action of Oil of Turpentine in the Cure of the Pain of Burns. PMID- 28999768 TI - Medical News. PMID- 28999770 TI - Current Medical Topics. PMID- 28999769 TI - Remarks on "Hepatic Phlebotomy". PMID- 28999772 TI - Anti-Febrin as Antipyretic and Antiseptic. PMID- 28999771 TI - Memo. on Dr. Greany's Report. PMID- 28999773 TI - Relative Rank. PMID- 28999774 TI - Notes on Some Surgical Cases Treated in the Charitable Dispensary, Mymensingh. PMID- 28999776 TI - Vital Statistics and Sanitary Notes. PMID- 28999775 TI - Appointments, Leave, &c. PMID- 28999777 TI - Transactions of Medical Societies. PMID- 28999778 TI - Strophanthus. PMID- 28999779 TI - Case of Obscure Heart Disease. PMID- 28999781 TI - Service Notes. PMID- 28999782 TI - Extirpation of the Spleen. PMID- 28999780 TI - Report on the Recent Prevalence of Malarial Fever in Chudderghat and Its Surrounding Suburbs, and on Their General Unhealthiness. PMID- 28999783 TI - A Gun-Shot Wound Treated in the Noakhalli Dispensary. PMID- 28999784 TI - Service Notes. PMID- 28999785 TI - Mr. McHale on Cannabis Indica for Dysentery. PMID- 28999786 TI - Vital Statistics and Sanitary Notes. PMID- 28999787 TI - Dr. Moore on an American Work Adapted to India. PMID- 28999788 TI - Appointments, Leave, &c. PMID- 28999789 TI - Penjdeh Swelling. PMID- 28999790 TI - Transactions of Medical Societies. PMID- 28999791 TI - Destruction versus Decomposition. PMID- 28999792 TI - The Diagnosis of Tropical Enteric Fever. PMID- 28999793 TI - Gun-Shot Wound: A Medico-Legal Case. PMID- 28999794 TI - A Case of Phosphorus Poisoning. PMID- 28999796 TI - Massage. PMID- 28999797 TI - Current Medical Topics. PMID- 28999795 TI - Precis of Operations Performed in the Wards of the 1st Surgeon, Medical College Hospital. PMID- 28999799 TI - Medical News. PMID- 28999798 TI - Mr. Bonnar on the Post-Molar Ulcer. PMID- 28999800 TI - Service Notes. PMID- 28999801 TI - On Successful Vaccination in the Plains during the Hot Season. PMID- 28999802 TI - Transactions of Medical Societies. PMID- 28999803 TI - The Treatment of Paraplegia. PMID- 28999804 TI - Prince of Wales' Hospital, Benares: Case of Ovariotomy. PMID- 28999806 TI - Surgery in the N. W. Provinces. PMID- 28999805 TI - The Treatment of Dysentery. PMID- 28999807 TI - Appointments, Leave, &c. PMID- 28999808 TI - A Case of Lawn Tennis Leg. PMID- 28999809 TI - Double Abscess in the Groins Treated by Tapping and Drainage. PMID- 28999810 TI - A Case of Triplets. PMID- 28999811 TI - Some Interesting and Peculiar Cases at Poonamallee, Madras from 1883-1885. PMID- 28999813 TI - A Vexed Question. PMID- 28999812 TI - Chittagong Dispensary-Cases Treated. PMID- 28999814 TI - Remarks on Fever Mortality at Deobund in 1884. PMID- 28999815 TI - Cholera at Sea. PMID- 28999816 TI - Current Medical Topics. PMID- 28999817 TI - Vital Statistics & Sanitary Notes. PMID- 28999818 TI - Medical News. PMID- 28999819 TI - Transactions of Medical Societies. PMID- 28999821 TI - Service Notes. PMID- 28999820 TI - A Case of Post-Mortem Parturition. PMID- 28999822 TI - Beri-Beri. PMID- 28999823 TI - Jungadh State Hospital: Cases of Accidental Explosions. PMID- 28999824 TI - The Progress and Distribution of Cholera Mortality in Calcutta. PMID- 28999825 TI - Appointments, Leave, &c. PMID- 28999826 TI - Vital Statistics and Sanitary Notes. PMID- 28999828 TI - Medical News. PMID- 28999827 TI - Remark on Fever Mortality in Deobund in 1884. PMID- 28999829 TI - The Sanitation of Calcutta. PMID- 28999830 TI - Current Medical Topics. PMID- 28999831 TI - Antipyrin in Acute Pyrexial Delirium. PMID- 28999833 TI - Precis of Operations Performed in the Wards of the First Surgeon, Medical College Hospital, during the Year 1886. PMID- 28999832 TI - Midnapore Dispensary: Three Cases of External Anthrax. PMID- 28999834 TI - Narail Charitable Dispensary: Case of Foreign Body. PMID- 28999835 TI - Current Medical Topics. PMID- 28999836 TI - Vital Statistics and Sanitary Notes. PMID- 28999837 TI - Tapping the Intestines. PMID- 28999838 TI - Service Notes. PMID- 28999839 TI - Medical News. PMID- 28999840 TI - Transactions of Medical Societies. PMID- 28999841 TI - Appointments, Leave, &c. PMID- 28999843 TI - College Appointments. PMID- 28999842 TI - The Progress and Distribution of Cholera Mortality in Calcutta. PMID- 28999844 TI - Medical Registration. PMID- 28999846 TI - Precis of Operations Performed in the Wards of the First Surgeon, Medical College Hospital during the Year 1886. PMID- 28999845 TI - Eden Hospital, Calcutta. PMID- 28999848 TI - Appointment, Leave, &c. PMID- 28999847 TI - Mr. Reid on the Interior Economy of Army Hospitals in India. PMID- 28999849 TI - Service Notes. PMID- 28999850 TI - Milk and Cheese Ptomaines. PMID- 28999851 TI - The Interior Economy of Army Hospitals in India. PMID- 28999853 TI - Lanoline Formulae. PMID- 28999852 TI - Dr. Fairland on the Diagnosis of Tropical Enteric Fever. PMID- 28999854 TI - Vital Statistics and Sanitary Notes. PMID- 28999855 TI - Cholera in Tonquin. PMID- 28999856 TI - Some Complicated Cases of Stone in the Bladder. PMID- 28999857 TI - Solon Station Hospital: Antipyrin Rash. PMID- 28999858 TI - Medical News. PMID- 28999859 TI - M. Verghese on the Diseases of Bellary. PMID- 28999860 TI - Transactions of Medical Societies. PMID- 28999861 TI - Some Interesting and Peculiar Cases at Poonamallee, Madras, from 1883 to 1885. PMID- 28999862 TI - Current Medical Topics. PMID- 28999863 TI - Appointments, Leave, &c. PMID- 28999864 TI - Medical Inspection. PMID- 28999865 TI - Royal Medical College, Epsom. PMID- 28999866 TI - Memorandum on Hill Diarrhoea, and Its Treatment by Perchloride of Mercury. PMID- 28999868 TI - Case of Traumatic Rupture of the Diaphragm. PMID- 28999867 TI - Hepatic Abscess in Children. PMID- 28999869 TI - Antipyrin in Neuralgia. PMID- 28999870 TI - Vital Statistics and Sanitary Notes. PMID- 28999871 TI - Current Medical Topics. PMID- 28999872 TI - Precis of Operations Performed in the Wards of the First Surgeon, Medical College Hospital, during the Year 1886. PMID- 28999873 TI - Royal Medical College, Epsom. PMID- 28999874 TI - Mayo Hospital, Nagpur-Case of Abdominal Injury. PMID- 28999875 TI - Sanitation in India. PMID- 28999876 TI - The Efficacy of Salicylic Acid in the Treatment of Scurvy. PMID- 28999877 TI - Transactions of Medical Societies. PMID- 28999878 TI - Case of Aneurism of Aorta, with Rupture of Spleen. PMID- 28999879 TI - Medical News. PMID- 28999880 TI - Service Notes. PMID- 28999881 TI - On Cholera. PMID- 28999883 TI - Current Medical Topics. PMID- 28999882 TI - Hepatic Exhaustion, and Its Influence on Health in the Tropics. PMID- 28999884 TI - Transactions of Medical Societies. PMID- 28999885 TI - Vital Statistics and Sanitary Notes. PMID- 28999887 TI - Extracts. PMID- 28999886 TI - Quacks and Emperics in Goa. PMID- 28999889 TI - The Medical Confessional. PMID- 28999888 TI - Cases of Puerperal Eclampsia. PMID- 28999891 TI - Appointments, Leave, &c. PMID- 28999890 TI - The Toxic Principles of Snake-Venoms. PMID- 28999892 TI - Service Notes. PMID- 28999893 TI - Remarks on Fever Mortality in Deobund in 1884. PMID- 28999894 TI - Fees for Medical Reports for Life Assurance. PMID- 28999896 TI - Ambulance Classes. PMID- 28999895 TI - The Treatment of Dysentery. PMID- 28999897 TI - Medical News. PMID- 28999898 TI - Medical Registration. PMID- 28999899 TI - Case of Cobra-Bite : Cure. PMID- 28999901 TI - The Treatment of Hill Diarrhoea. PMID- 28999900 TI - Notes on an Epidemic of Cholera in Purnia District: February-June 1891. PMID- 28999903 TI - Medical News, &c. PMID- 28999902 TI - Permanent Subcutaneous Suture of the Patella for Ununited Fracture. PMID- 28999904 TI - Appointments, Leave, &c. PMID- 28999905 TI - Transactions of Medical Societies. PMID- 28999906 TI - Abdominal Surgery at the Eden Hospital, Calcutta, during the Year 1891. PMID- 28999907 TI - Ophthalmic Cases at the Darjeeling Dispensary. PMID- 28999908 TI - Short-Hand Writing. PMID- 28999909 TI - Deposit of Yellow Arsenic on the Endocardium in a Case of a Arsenical Poisoning: Reported with the Kind Permission of Dr. Warden. PMID- 28999910 TI - Brigade-Surgeon McLeod. PMID- 28999911 TI - Cure for Scorpion Sting. PMID- 28999912 TI - Vital Statistics & Sanitation. PMID- 28999913 TI - Service Notes, &c. PMID- 28999914 TI - Current Medical Topics. PMID- 28999915 TI - A Case of Snake-Bite: Treatment by Hypodermic Injection of Sulphate of Strychnia: Recovery. PMID- 28999916 TI - Recurrent Glio-Sarcoma in the Orbit. PMID- 28999917 TI - Cholera in Paris. PMID- 28999918 TI - Selected Cases from Barisal. PMID- 28999919 TI - A Study of Indian Fevers. PMID- 28999920 TI - Notes on Some Surgical Cases. PMID- 28999922 TI - Appointments, Leave, &c. PMID- 28999921 TI - Case of Non-Union in a Fractured Clavicle. PMID- 28999923 TI - Vital Statistics and Sanitation. PMID- 28999924 TI - The Treatment of Cholera by Strychnine. PMID- 28999925 TI - The Modern Apollo Smintheus. PMID- 28999926 TI - Medical News, &c. PMID- 28999928 TI - Current Medical Topics. PMID- 28999927 TI - Service Notes, &c. PMID- 28999929 TI - Case of Chronic Ulcer of the Stomach: Haematemesis-Death. PMID- 28999930 TI - Transactions of Medical Societies. PMID- 28999931 TI - On the Treatment of Bubo. PMID- 28999932 TI - Transactions of Medical Societies. PMID- 28999933 TI - The Principles of Rational Medicine: A Farewell Lecture Delivered to the Students of the Calcutta Medical College. PMID- 28999935 TI - Notes on a Case of Aneurism of Anterior Division of Superficial Temporal Artery. PMID- 28999934 TI - The Dufferin Fund. PMID- 28999936 TI - Service Notes. PMID- 28999937 TI - Rupture of the Internal Semilunar Cartilage of the Knee-Joint. PMID- 28999938 TI - Report on Fever on the Chaman Extension Railway. PMID- 28999939 TI - Appointments, Leave, &c. PMID- 28999940 TI - Vital Statistics & Sanitation. PMID- 28999941 TI - Anchylostoma Duodenalis on Tea Gardens. PMID- 28999942 TI - Pregnancy with Diabetes Mellitus and Corpulence: Death of Foetus in Utero at Full Term. PMID- 28999943 TI - Scrotal Elephantiasis. PMID- 28999944 TI - Keloid Growths Following Vaccination. PMID- 28999945 TI - Goitre or Bronchocele and Its Curative Treatment. PMID- 28999947 TI - Medical News. PMID- 28999948 TI - A Case of Local Spasms of Face and Neck. PMID- 28999946 TI - Use of Bhuphali (Corchorus Fascienlatus). PMID- 28999950 TI - Hypnotism. PMID- 28999949 TI - Hypnotism and Suggestion. PMID- 28999951 TI - Current Medical Topics. PMID- 28999952 TI - Transactions of Medical Societies. PMID- 28999953 TI - Strychnine in Cholera Cases. PMID- 28999954 TI - Urine - Increased by Large Doses of Quinine. PMID- 28999955 TI - Case of Kala-Azar in the Insane. PMID- 28999957 TI - Bacteriological Examinations of Butter. PMID- 28999956 TI - Fits of Gravel Corresponding with Appearance of New Moon. PMID- 28999958 TI - Current Medical Topics. PMID- 28999959 TI - An Analysis of 500 Litholapaxies Performed at the Indore Charitable Hospital, Central India, with Remarks. PMID- 28999960 TI - Medical News, &c. PMID- 28999961 TI - Notes on Anchylostomiasis, a Resume of a Report on the Diseases Known in Assam as Kala-Azar and Beri-Beri. PMID- 28999962 TI - A Case of Excision of the Lower Jaw. PMID- 28999964 TI - Appointments, Leave, &c. PMID- 28999963 TI - Unusual Sites for Lipomata. PMID- 28999966 TI - Vital Statistics & Sanitation. PMID- 28999965 TI - Service Notes, &c. PMID- 28999967 TI - Dr. Crombie's Summary of the Opium Discussion. PMID- 28999968 TI - Notes ou Chlorine as an Antidote for Cobra Venom. PMID- 28999969 TI - The Discussion at the Calcutta Medical Society on the Effects of the Habitual Use of Opium on the Human Constitution. PMID- 28999971 TI - Curious Case of Congenital Malformation. PMID- 28999970 TI - Abstract of an Address on Famine: Delivered at the London Epidemiological Society, 16th December 1891, Surgeon-General Ewart, President. PMID- 28999973 TI - Midwifery among the Alaskan Indians. PMID- 28999972 TI - Action of the Sterno-Cleido-Mastoid Muscles. PMID- 28999974 TI - Service Notes. PMID- 28999975 TI - Notes on an Epidemic of Cholera in the Purnia District: February-June 1891. PMID- 28999976 TI - Antipyrin and Sp. Eth. Netrosi. PMID- 28999978 TI - The New Titles. PMID- 28999977 TI - Appointments, Leave, &c. PMID- 28999979 TI - Case of Gunshot Wound of the Abdomen. PMID- 28999980 TI - Current Medical Topics. PMID- 28999981 TI - Sir Spencer Wells' Visit to Calcutta. PMID- 28999982 TI - Jambul in Diabetes Mellitus. PMID- 28999983 TI - Treatment of Dysentery. PMID- 28999984 TI - Hypnotism and Suggestion. PMID- 28999985 TI - Medical News. PMID- 28999986 TI - Vital Statistics and Sanitation-Vital Statistics, Sanitation, and Vaccination in Bengal. PMID- 28999987 TI - Erratum: Malarial Fevers. AB - [This corrects the article on p. 353 in vol. 26.]. PMID- 28999989 TI - Kala-Azar and Beri-Beri in Assam. PMID- 28999988 TI - Notes on Cases of Abdominal Surgery. PMID- 28999990 TI - Transactions of Medical Societies. PMID- 28999991 TI - Mahubari District Hospital Cases. PMID- 28999992 TI - Spontaneous Fracture of Femur Following Gunshot Wound of Thigh. Amputation: Recovery. PMID- 28999993 TI - Stone in the Bladder Successfully Removed by Suprapublic Lithotomy. PMID- 28999994 TI - Case of Enormous Hydrocephalus. PMID- 28999995 TI - Parke's Memorial Prize. PMID- 28999996 TI - Erythrophlein. PMID- 28999997 TI - Inguinal Colotomy; a Suggestion. PMID- 28999998 TI - A Case of Litholapaxy with a Peculiar Complication. PMID- 28999999 TI - Current Medical Topics. PMID- 29000000 TI - Entero-Septic Fevers. PMID- 29000001 TI - Note of Some Observations on the Morphology of the Blood in Cases of Malarial Infection. PMID- 29000002 TI - Dysentery and the Amocha Coli. PMID- 29000003 TI - Select Cases from the Barisaul Charitable Hospital and Dispensary. PMID- 29000004 TI - Service Notes, &c. PMID- 29000005 TI - Clinical Notes on Diseases of the Throat, Nose and Ear. PMID- 29000006 TI - Transactions of Medical Societies. PMID- 29000008 TI - Medical News, &c. PMID- 29000007 TI - On the Study of Indigenous Drugs. PMID- 29000009 TI - Vital Statistics & Sanitation. PMID- 29000010 TI - Notes on an Antidote for Snake-Poison. PMID- 29000011 TI - The Relation of Elevation to Hill Diarrhoea. PMID- 29000012 TI - Appointments, Leave, &c. PMID- 29000013 TI - The Annual Report of the Sanitary Commissioner with the Government of India for 1890. PMID- 29000014 TI - A Peculiar Form of Hysteria in the Male. PMID- 29000015 TI - The Treatment of Hill Diarrhoea. PMID- 29000016 TI - Medical News, &c. PMID- 29000017 TI - A Case of Gunshot Wound of the Knee-Joint. PMID- 29000018 TI - Current Medical Topics. PMID- 29000019 TI - Notes on an Antidote for Snake Poison. PMID- 29000020 TI - Myxoedema. PMID- 29000021 TI - Plastic Operation for Upper and Lower Lip-Cheiloplastic Operation. PMID- 29000022 TI - Indigenous Drugs of India. PMID- 29000024 TI - Vital Statistics and Sanitation. PMID- 29000023 TI - Dicephalous Child. PMID- 29000025 TI - Transactions of Medical Societies. PMID- 29000027 TI - Competitive Physical Examination. PMID- 29000026 TI - Excision of the Inner Two-Thirds of the Right Clavicle for Sarcoma. PMID- 29000029 TI - Appointments, Leave, &c. PMID- 29000028 TI - Malarial Blood. PMID- 29000030 TI - Enteric Fever in the European Army. PMID- 29000031 TI - Service Notes, &c. PMID- 29000032 TI - Special Supplement to "Indian Medical Gazette" April 1892. PMID- 29000033 TI - Medical News. PMID- 29000034 TI - Fetch the Doctor. PMID- 29000035 TI - Anchylostoma Duodenalis on Tea Gardens. PMID- 29000036 TI - A Severe Case of Worms (Ascaris Lumbricoides). PMID- 29000037 TI - Farewell. PMID- 29000038 TI - Notes on an Epidemic of Cholera in the Burma District: February-June 1891. PMID- 29000039 TI - Presidency General Hospital: Four Cases of Alcoholic Neuritis. PMID- 29000040 TI - On the Passage from the Human Intestine of Swarms of Maggots and an Explanation of the Source from Which They Are Derived. PMID- 29000041 TI - Vital Statistics & Sanitation. PMID- 29000042 TI - Service Notes. PMID- 29000043 TI - Report on Fever on the Chaman Extension Railway. PMID- 29000044 TI - Transactions of Medical Societies. PMID- 29000045 TI - Appointments, &c. PMID- 29000046 TI - Current Medical Topics. PMID- 29000047 TI - Select Cases from the Charitable Dispensary and Hospital, Noakhally. PMID- 29000049 TI - Penetrating Wound of the Abdomen - Laparotomy. PMID- 29000048 TI - Transactions of Medical Societies. PMID- 29000050 TI - 1891. PMID- 29000051 TI - A Case of Paraplegia with Partial Cervical Paralysis-The Result of Malarial Poisoning. PMID- 29000052 TI - Current Medical Topics. PMID- 29000054 TI - Vital Statistics and Sanitation. PMID- 29000053 TI - Report on Fever on the Chaman Extension Railway. PMID- 29000056 TI - Treatment of Post - Partum Haemorrhage. PMID- 29000055 TI - The New Theory of Heredity: A Synopsis. PMID- 29000057 TI - Appointments, Leave, &c. PMID- 29000058 TI - The 1884 Military Class Students of the Calcutta Medical College. PMID- 29000060 TI - A Preliminary Note on OEsophagostoma Columbeanum Curtici. PMID- 29000059 TI - Service Notes. PMID- 29000061 TI - The Treatment of Dysentery. PMID- 29000062 TI - A Case of Complete Rupture of the Small Intestine. PMID- 29000064 TI - Vital Statistics & Sanitation. PMID- 29000063 TI - Medical News. PMID- 29000065 TI - Current Medical Topics. PMID- 29000066 TI - A Fatal Case of Purpura Haemorrhagica in a Child. PMID- 29000067 TI - Microscopical Observations in the Blood and Excreta in Cholera Cases. PMID- 29000068 TI - Penetrating Wounds of the Abdominal Cavity: Treatment-Recovery. PMID- 29000069 TI - A Case of Large Hydrocele. PMID- 29000070 TI - The Effects of Quinine Alone and Combined in the Treatment of Ague. PMID- 29000071 TI - Appointments, Leave, &c. PMID- 29000072 TI - Abdominal Surgery at the Eden Hospital, Calcutta, during 1891. PMID- 29000073 TI - The Crusade against Opium. PMID- 29000074 TI - Therapeutic Action of Certain Herbs and Vegetables. PMID- 29000075 TI - Chemical Factors in Causation of Disease. PMID- 29000076 TI - Medical News, &c. PMID- 29000077 TI - Transactions of Medical Societies. PMID- 29000078 TI - A Case of Mineral or Calcareous Degeneration of the Crystalline Lens. PMID- 29000079 TI - Grafting. PMID- 29000080 TI - Inhalation of Oxygen in Cases of Pneumonia. PMID- 29000081 TI - Cases of Febricula with Abdominal Tenderness. PMID- 29000083 TI - Service Notes, &c. PMID- 29000082 TI - Notes on Two Cases of Aphonia. PMID- 29000084 TI - Notes on Anchylostomiasis. Resume of a Report on the Diseases Known in Assam as Kala-Azar and Beri-Beri. PMID- 29000086 TI - Stricture of the Urethra after Lateral Lithotomy. PMID- 29000085 TI - Two Cases of Impermeable Stricture. PMID- 29000088 TI - Vital Statistics and Sanitation. PMID- 29000087 TI - Hiccough in Ague. PMID- 29000089 TI - Current Medical Topics. PMID- 29000090 TI - Transactions of Medical Societies. PMID- 29000091 TI - The Pathogenic Fungus of Malaria. PMID- 29000093 TI - Clinical Notes on Diseases of the Throat, Nose and Ear. PMID- 29000092 TI - The Amoeba Coli: Its Relations to Dysentery and Tropical Suppurative Hepatitis. PMID- 29000095 TI - Appointments. PMID- 29000094 TI - A Note on the Pathology of Kala-Azar or Beri-Beri of Assam. PMID- 29000096 TI - Recent German Researches on Malaria: Its Treatment by Methylene Blue. With Introductory Remarks. PMID- 29000097 TI - Ainhum of a Supernumerary Finger. PMID- 29000098 TI - Leave. PMID- 29000099 TI - Typhus Fever in the Khojak Pass. PMID- 29000100 TI - The Protection of Seamen in Port from Heat and Sun. PMID- 29000101 TI - The Sewers of Calcutta. PMID- 29000102 TI - Service Notes. PMID- 29000103 TI - Malarial Infection. PMID- 29000104 TI - Jail Administration Reform. PMID- 29000105 TI - Clinical Notes on Cases of Enteric Fever. PMID- 29000107 TI - Treatment of Poisoning by Cocaine. PMID- 29000106 TI - The Bacteriology of the "Crofton Hall" Tragedy. PMID- 29000108 TI - Transfers-Promotions-Leave, &c. - Dismissal-Language. PMID- 29000109 TI - Appointments. PMID- 29000110 TI - Note Regarding the Prevalence of the Dochmius Duodenalis. PMID- 29000112 TI - Transactions of Medical Societies. PMID- 29000111 TI - Notes on Some Surgical Cases. PMID- 29000114 TI - Note on the Bacteriology of the "Crofton Hall" Tragedy. PMID- 29000115 TI - A Few Surgical Cases. PMID- 29000113 TI - Enteric Fever. PMID- 29000116 TI - A Note on the Pathology of Kala-Azar, or Beri-Beri, of Assam. PMID- 29000117 TI - Current Medical Topics. PMID- 29000118 TI - Notes on the Diagnosis and Treatment of Enteric Fever. PMID- 29000119 TI - Note of a Successful Case of Extirpation of Penis for Cancer. PMID- 29000121 TI - New Treatment for Trachoma. PMID- 29000120 TI - Enteric Fever in the European Army. PMID- 29000122 TI - Abdominal Wound-Intestinal and Omental Hernia. PMID- 29000124 TI - Vital Statistics and Sanitary Notes. PMID- 29000123 TI - Precis of Operations Performed in the Wards of the 1st Surgeon, Medical College Hospital, during the Year 1888. PMID- 29000126 TI - The Dose of Arsenic for Infants. PMID- 29000125 TI - The Twenty-Fourth Annual Report of the Sanitary Commissioner with the Government of India for 1887. PMID- 29000127 TI - Correspondence. PMID- 29000128 TI - Service Notes. PMID- 29000129 TI - A Sketch of the Medical and Surgical Experiences of the War of the Rebellion in America during the Years 1861-65. PMID- 29000131 TI - Transactions of Medical Societies. PMID- 29000130 TI - Perchloride of Mercury and Cannabis Indica in Dysentery. PMID- 29000132 TI - Appointments, Leave, &c. PMID- 29000133 TI - Medical Registration. PMID- 29000135 TI - Hot Water as a Haemostatic. PMID- 29000134 TI - Current Medical Topics. PMID- 29000136 TI - Fevers and Their Rational Treatment by Antipyretics. PMID- 29000137 TI - Medical News. PMID- 29000138 TI - The Bacillus Typhosus. PMID- 29000139 TI - The Fruits of Sanitation. PMID- 29000140 TI - Wound of Neck and Spine-Recovery. PMID- 29000141 TI - Medical News. PMID- 29000142 TI - Childbed Fever. PMID- 29000143 TI - The Pasteur Institute. PMID- 29000144 TI - Service Notes. PMID- 29000145 TI - Medico-Legal Points Involved in a Recent State Trial-Homicide and Suicide: Empress v. Sudhabode Bhattacharji. PMID- 29000146 TI - The Rigor Mortis Enquiry. PMID- 29000147 TI - Penetrating Punctured Wound of Skull-Recovery. PMID- 29000148 TI - Appointments, Leave, &c. PMID- 29000149 TI - A Case of Throttling. PMID- 29000150 TI - Vital Statistics and Sanitary Notes. PMID- 29000151 TI - Tape Worm in the Crow. PMID- 29000153 TI - Current Medical Topics. PMID- 29000152 TI - Three Cases of Strangulated Scrotal Hernia with Remarks. PMID- 29000155 TI - Very Hot Compresses in Surgical Practice-Hot Water in Epistaxis. PMID- 29000154 TI - Transactions of Medical Societies. PMID- 29000156 TI - Eight Cases of Saponification. PMID- 29000157 TI - The Riviera as a Winter Health Resort. PMID- 29000158 TI - The Commission on Leprosy. PMID- 29000159 TI - On the Treatment of a Case of Cholera in an European by a Deep Subcutaneous Injection of Perchloride of Mercury. PMID- 29000161 TI - Reorganization of Medical Service in India. PMID- 29000160 TI - A Sketch of the Medical and Surgical Experiences of the War of the Rebellion in America during the Years 1861-65. PMID- 29000162 TI - Phenacetin and Thallin for Children. PMID- 29000163 TI - A Case of Rupture of the Right Phrenic Nerve Followed by Instantaneous Death. PMID- 29000164 TI - Appointments, Leave, &c. PMID- 29000165 TI - Effects of Excessive Tea-Drinking. PMID- 29000166 TI - Vital Statistics and Sanitation. PMID- 29000167 TI - The Leper Bill. PMID- 29000168 TI - Injections for Obstinate Leucorrhoea. PMID- 29000169 TI - Medical News. PMID- 29000170 TI - Two Cases of Traumatic Tetanus. PMID- 29000172 TI - A New Diagnostic Sign in Typhoid Fever. PMID- 29000171 TI - Notes on the Comparative Value of Antipyrin, Antifebrin, and Phenacetin as Antipyretics. PMID- 29000173 TI - Current Medical Topics. PMID- 29000174 TI - Transactions of Medical Societies. PMID- 29000176 TI - Use of Corrosive Sublimate in Laparotomies. PMID- 29000175 TI - Notes on a Case of Strangulated Inguinal Hernia. PMID- 29000178 TI - Bacterioscopy in the Diagnosis of Meningitis Cerebro-Spinalis. PMID- 29000177 TI - Enteric Fever in India. PMID- 29000180 TI - Menthol in Pruritus. PMID- 29000179 TI - Migraine. PMID- 29000181 TI - Service Notes. PMID- 29000182 TI - Poisoning by Preserved Meat Which Had Become Tainted in the Tins. PMID- 29000184 TI - Case of Compound Fracture of the Skull. PMID- 29000183 TI - The Royal Commission on Vaccination. PMID- 29000185 TI - The Importance of Manure Heaps and Poultry in the Etiology of Diphtheria. PMID- 29000186 TI - Brief Notes on Three Hundred and Five Cases of Drowning. PMID- 29000187 TI - Current Medical Topics. PMID- 29000188 TI - Masso Therapeutics and Scorpion Stings. PMID- 29000189 TI - Notes on an Outbreak of Cholera in the Town of Burisal in December 1888. PMID- 29000191 TI - Lanolin Urethral Injections. PMID- 29000190 TI - Vital Statistics and Sanitation. PMID- 29000192 TI - Case of Tetanus Following Dog Bite. Treatment-Recovery. PMID- 29000193 TI - Case of Laryngismus Stridulus. PMID- 29000194 TI - A Note on the Use of Perchloride of Mercury Gauze as a Substitute for Sponges in Abdominal Surgery. PMID- 29000195 TI - Contra-Indications for the Use of Antipyrin during the Menstrual Period. PMID- 29000196 TI - A Few Points on Enteric Fever as Illustrated by the Army Medical Department Report for 1886 and the Annual Report of the Sanitary Commissioner with the Government of India. PMID- 29000197 TI - Tetanus. PMID- 29000198 TI - The Auto-Toxicity of Snakes. PMID- 29000200 TI - Medical News. PMID- 29000199 TI - Appointments, Leave, &c. PMID- 29000201 TI - Service Notes. PMID- 29000202 TI - Transactions of Medical Societies. PMID- 29000203 TI - The Cocoanut as an Anthelmintic. PMID- 29000204 TI - Cremation of Garbage in Savannah. PMID- 29000205 TI - Transactions of Medical Societies. PMID- 29000206 TI - Current Medical Topics. PMID- 29000207 TI - Precis of Operations Performed in the Wards of the 1st Surgeon, Medical College Hospital, during the Year 1888. PMID- 29000209 TI - Service Notes. PMID- 29000208 TI - Rhinoscleroma. PMID- 29000211 TI - Bayu, Pitta, Kapha. PMID- 29000210 TI - Medical News. PMID- 29000213 TI - Poisoning by Strychinos Nux Vomica. PMID- 29000212 TI - Appointments, Leave, &c. PMID- 29000214 TI - Intubation vs. Tracheotomy. PMID- 29000215 TI - Richards on Pasteurism. PMID- 29000216 TI - Vital Statistics and Sanitary Notes. PMID- 29000217 TI - Cases from Practice. PMID- 29000219 TI - Appointments, Leave, &c. PMID- 29000218 TI - Beri-Beri: Reprinted from the Transactions of the, South Indian Branch of the British Medical Association. PMID- 29000221 TI - Caffein in Diseases of the Lung. PMID- 29000220 TI - Formula for Hysterical Hyperaethesia, Vomiting, and Spasmodic Conditions. PMID- 29000222 TI - The Anthrax Question in India. PMID- 29000223 TI - Vital Statistics and Sanitary Notes. PMID- 29000224 TI - Presidency General Hospital-Case of Diabetes Insipidus. PMID- 29000226 TI - The Use of Naphthol in the Paris Hospitals. PMID- 29000225 TI - On the Value of Antifebrin and Quinine in Typhoid Fever. PMID- 29000227 TI - Medical News. PMID- 29000228 TI - Current Medical Topics. PMID- 29000229 TI - Incompatible Antiseptics. PMID- 29000230 TI - An Early Sign of Endocarditis. PMID- 29000231 TI - Service Notes. PMID- 29000232 TI - The Use of Certain Medicaments with or without Precedent, Dilatation in the Treatment of Endometritis, Metritis, Fibromyomata and Fluxions of the Uterus. PMID- 29000234 TI - Notes on Phenomena Occurring after Death. PMID- 29000233 TI - Enteric Fever Lesions in Dogs: A Contribution Towards the Investigation of the Prevalence of Enteric Fever in Cantonments. PMID- 29000235 TI - Tank-Filling with Garbage in Calcutta. PMID- 29000236 TI - The Need of an Imperial Sanitary Board. PMID- 29000237 TI - Phthisis from House Sweepings. PMID- 29000238 TI - Cure of a Case of Leprosy. PMID- 29000239 TI - Novel Means of Diagnosis of Perforation of the Membrana Tympani. PMID- 29000240 TI - Transactions of Medical Societies. PMID- 29000241 TI - Eden Hospital - Case of Hyperpyrexia Treated by the Cold Bath. PMID- 29000242 TI - Infection of an Infant through the Milk of a Tuberculous Nurse. PMID- 29000243 TI - Antiseptics in Ophthalmic Surgery. PMID- 29000244 TI - Notes on Cholera. PMID- 29000245 TI - Identification of Poisonous Snakes. PMID- 29000246 TI - Service Notes. PMID- 29000247 TI - Abstract of the Hyderabad Chloroform Commission's Report. PMID- 29000249 TI - The Bengal Medical Service One Hundred Years Ago. PMID- 29000248 TI - Abrus Poisoning. PMID- 29000250 TI - A Case of Amputation of the Thigh. PMID- 29000251 TI - Appointments, Leave, &c. PMID- 29000252 TI - Tragia Cannabina & Involucrata. PMID- 29000254 TI - Suprapubic Prostatectomy. PMID- 29000253 TI - A Temperature of 112.8 degrees F. Followed by Recovery. PMID- 29000256 TI - Medical News. PMID- 29000255 TI - Current Medical Topics. PMID- 29000257 TI - Vital Statistics and Sanitation. PMID- 29000258 TI - Sanitation of Bombay. PMID- 29000259 TI - The Use of Pessaries. PMID- 29000260 TI - Ruptures of the Liver Complicated with Ruptures of Other Internal Organs. PMID- 29000261 TI - Historical Retrospects of Sanitation: A Lecture Delivered at the Madrasa-I-Alaga, Hyderabad, Deccan. PMID- 29000262 TI - Transactions of Medical Societies. PMID- 29000263 TI - Transactions of Medical Societies. PMID- 29000264 TI - Service Notes. PMID- 29000265 TI - Ovarian Dropsy-Tapping-Extraction of Cyst-Death. PMID- 29000267 TI - A Sketch of the Medical and Surgical Experience of the War of the Rebellion in America during the Year 1861-65. PMID- 29000266 TI - Hot Water as a Haemostatic. PMID- 29000268 TI - Four Cases of Rhino-Scleroma. PMID- 29000270 TI - Medical News. PMID- 29000269 TI - Deep-Seated Tumour of the Neck-Successful Removal. PMID- 29000271 TI - Current Medical Topics. PMID- 29000272 TI - Appointments, Leave, &c. PMID- 29000273 TI - 1888. PMID- 29000274 TI - Vital Statistics and Sanitary Notes. PMID- 29000275 TI - Vienna as a Medical School for Post - Graduate Work. PMID- 29000276 TI - Pharyngitis. PMID- 29000278 TI - Unusual Effects of Chloroform. PMID- 29000277 TI - Service Notes. PMID- 29000280 TI - Infectious Jaundice. PMID- 29000279 TI - The Treatment of Cholera with Oil of Eucalyptus. PMID- 29000281 TI - Origin of the Vesicular Respiratory Murmur. PMID- 29000282 TI - Two Successful Cases of Lacerated Wounds of the Abdomen. PMID- 29000283 TI - A Hospital for Sick and Lame Animals in Calcutta. PMID- 29000285 TI - Notes of Cases Treated in the Puri Pilgrim Hospital. PMID- 29000284 TI - Ruptures of the Spleen. PMID- 29000287 TI - The Late Professor David Boyes Smith. PMID- 29000286 TI - Vital Statistics and Sanitary Notes. PMID- 29000289 TI - Transactions of Medical Societies. PMID- 29000288 TI - How Far May a Cow Become Tuberculous before Her Milk Becomes Dangerous as an Article of Food. PMID- 29000290 TI - Treatment of Gout. PMID- 29000291 TI - Exalgine in Neuralgias. PMID- 29000292 TI - Appointments, Leave, &c. PMID- 29000293 TI - Bulau's Operation for Empyema. PMID- 29000295 TI - Current Medical Topics. PMID- 29000294 TI - The Etiology of Cholera. PMID- 29000296 TI - Heart Complications in Gonorrhoea. PMID- 29000298 TI - Treatment of Chronic Cystitis in Women. PMID- 29000297 TI - Successful Ovariotomy. PMID- 29000299 TI - Death from Sulphonal. PMID- 29000300 TI - Value of the Diagnostic Tampon in Chronic Endometritis. PMID- 29000301 TI - A Geographical Sketch of Leprosy and the Question of Its Relation to the Consumption of Fish in Bengal, Behar, Orissa, and Assam. PMID- 29000302 TI - Delivery by the Short Forceps in a Case of Protracted Labour and Rigid Os Uteri. PMID- 29000303 TI - The Bacillus of Tetanus. PMID- 29000304 TI - Transactions of Medical Societies. PMID- 29000305 TI - Three Fatal "Head" Cases with Post-Mortem Examinations. PMID- 29000306 TI - Diagnostic Significance of Increase of the Knee Phenomenon and of the Foot Clonus. PMID- 29000307 TI - Fatal Intoxication with Bichloride of Mercury. PMID- 29000308 TI - Medical News. PMID- 29000309 TI - Case of Arrow-Wound. PMID- 29000311 TI - Appointments, Leave, &c. PMID- 29000312 TI - Current Medical Topics. PMID- 29000310 TI - The Report of Lord Camperdown's Committee. PMID- 29000313 TI - Formation of Ptomaines and Toxines by Pathogenic Bacteria. PMID- 29000314 TI - Vital Statistics and Sanitation. PMID- 29000315 TI - Treatment of Cholera with Salol. PMID- 29000316 TI - Cocaine Poisoning. PMID- 29000317 TI - Incineration. PMID- 29000318 TI - Brain Centre for Bladder Movement. PMID- 29000319 TI - Extirpation of the Pancras and Diabetes. PMID- 29000320 TI - The Bacilli of Cholera, Typhoid Fever and Tuberculosis in Milk, Butter, and Cheese. PMID- 29000321 TI - Thoughts and Queries. PMID- 29000322 TI - The Kashmir Cholera Epidemic of 1888. PMID- 29000323 TI - Notes on One Hundred and Eleven Cases of Ruptures of Internal Organs. PMID- 29000324 TI - Service Notes. PMID- 29000325 TI - A Case of Latent Diabetes. PMID- 29000326 TI - Medical News. PMID- 29000328 TI - Modifications of Egg-Albumen. PMID- 29000327 TI - Incompatibility of Antipyrine with Cinchona and Chloral Hydrate. PMID- 29000329 TI - Medical Jurisprudence in India. PMID- 29000330 TI - Unusual Distribution of Herpes Zosters. PMID- 29000331 TI - Treatment of Cholera by Subcutaneous Injections. PMID- 29000332 TI - Vital Statistics and Sanitation. PMID- 29000334 TI - Current Medical Topics. PMID- 29000333 TI - The Report of Lord Camperdown's Committee. PMID- 29000335 TI - Appointments, Leave, &c. PMID- 29000336 TI - Sterilising Milk. PMID- 29000337 TI - Case of Oleander Poisoning. PMID- 29000338 TI - Permanganate of Potassium and Chloroform in Snake Bites. PMID- 29000339 TI - Case of Lithotomy. PMID- 29000340 TI - Contributions to Indian Materia Medica: "Our Indigenous Medical Plants Deserve Far More Study Than They Have Yet Received." On the Medicinal Properties of Some of the Indigenous Plants of Southern India. PMID- 29000341 TI - Bromide of Potassium as an Antidote to Chloroform. PMID- 29000342 TI - Historical Retrospect of Sanitation: A Lecture Delivered at the Madrasa-I-Alaga, Hyderabad, Deccan. PMID- 29000343 TI - Transactions of Medical Societies. PMID- 29000344 TI - Agaric Acid : A New Drug for Night Sweating. PMID- 29000346 TI - Incompatibility of Morphine with Prussic Acid. PMID- 29000345 TI - Case of Incised Wound of Superior Maxillae. PMID- 29000348 TI - Glaucoma and Its Treatment. PMID- 29000347 TI - Antipyrine Checking Convulsions in a Dog. PMID- 29000349 TI - Case of Concealment of Sex. PMID- 29000350 TI - Prevention of Bed-Sores. PMID- 29000351 TI - Some Quack Remedies. PMID- 29000352 TI - Experiments with the Revd. Mr. Lorbeer's Antidote (Tiriyaq) to Cobra-Venom. PMID- 29000354 TI - Medical News. PMID- 29000353 TI - A Local and Circumscribed Outbreak of Cholera, Bearing a Special Relation to Food. PMID- 29000356 TI - Lectures on Sanitation to British Troops, Fort William. PMID- 29000355 TI - Historical Retrospect of Sanitation: A Lecture Delivered at the Madras A-I-Alaga, Hyderabad, Deccan. PMID- 29000357 TI - On Cold Abscesses after Malaria. PMID- 29000358 TI - Foreign Body in the Subcutaneous Connective Tissue. PMID- 29000359 TI - Appointments, Leave, &c. PMID- 29000360 TI - Service Notes. PMID- 29000361 TI - Accouchement after Extirpation of the Sacrum. PMID- 29000362 TI - Recent Views on Diabetes. PMID- 29000363 TI - The Late Professor David Boyes Smith. PMID- 29000364 TI - The Late Professor David Boyes Smith. PMID- 29000365 TI - Transactions of Medical Societies. PMID- 29000367 TI - Contagious Diseases in Cantonments. PMID- 29000366 TI - Notes on Phenacetin in the Treatment of Continuous & Malarious Fevers, and on Sulphonal as an Hypnotic. PMID- 29000368 TI - Vital Statistics and Sanitation. PMID- 29000369 TI - An Ingenious Malingerer. PMID- 29000371 TI - Current Medical Topics. PMID- 29000370 TI - Severe Puerperal Hemorrhage Successfully Treated by Iodoform Gauze Tampons. PMID- 29000373 TI - On the Formation of Adipocere. PMID- 29000372 TI - A Case of Enteric Fever. PMID- 29000374 TI - Medical News. PMID- 29000375 TI - Influenza. PMID- 29000376 TI - Antipyretic Action of Soda Bicarbonate. PMID- 29000378 TI - Transactions of Medical Societies. PMID- 29000377 TI - Current Medical Topics. PMID- 29000379 TI - Typhoid Fever. PMID- 29000380 TI - Rupture of Spleen; Death Half an Hour after. PMID- 29000382 TI - Medical Education. PMID- 29000381 TI - Contributions to Our Knowledge of Non-Typical Typhoid Fever. PMID- 29000383 TI - Entero-Malarial Fever. PMID- 29000384 TI - Service Notes. PMID- 29000385 TI - A Case of Hepatic Abscess in an European Female Child 20 Months Old. PMID- 29000387 TI - Appointments, Leave, &c. PMID- 29000386 TI - The Hour at Which Death Most Usually Occurs. PMID- 29000388 TI - Precis of Operations Performed in the Wards of the First Surgeon, Medical College Hospital, during the Year 1889. PMID- 29000389 TI - Chloroform and Fatty Heart. PMID- 29000391 TI - Current Medical Topics. PMID- 29000390 TI - Cerebro Spinal Fever: Extract from Sanitary Report of Hazaribagh Jail for the Year 1889. PMID- 29000392 TI - The Treatment of Burns of the Eye. PMID- 29000394 TI - Leprosy and Syphilis. PMID- 29000393 TI - Two Cases Illustrating Age with Reference to the Effects of Snake-Bite. PMID- 29000395 TI - Precis of Operations Performed in the Wards of the First Surgeon, Medical College Hospital, during the Year 1889. PMID- 29000396 TI - Notes on Anaemia: Its Pathology and Treatment. PMID- 29000397 TI - Transactions of Medical Societies. PMID- 29000399 TI - Service Notes. PMID- 29000398 TI - Thirteen Sudden Deaths from Suffocation. PMID- 29000400 TI - Perforating Gunshot Wounds of the Chest and of the Wrist Joint, Both in the Same Patient and Followed by Recovery. PMID- 29000401 TI - Microscopical Society of Calcutta. PMID- 29000403 TI - Child-Wives. PMID- 29000402 TI - Medical News. PMID- 29000404 TI - Current Medical Topics. PMID- 29000405 TI - A Case of Epileptiform Fits. PMID- 29000406 TI - Service Notes. PMID- 29000407 TI - Sewage Disposal in Bengal. PMID- 29000409 TI - Malarial Fevers and Influenza at Fort Tregear. PMID- 29000408 TI - The Treatment of Cholera. PMID- 29000410 TI - Tait versus Lister. PMID- 29000411 TI - Cholera and Phthisis. PMID- 29000412 TI - Medical News. PMID- 29000413 TI - Method of Operation for Cataract in the Bijnor Dispensary with the Result of 100 Cases in 1889. PMID- 29000414 TI - Cholera Diffusion. PMID- 29000416 TI - Transactions of Medical Societies. PMID- 29000415 TI - Notes on a Case of Ovariotomy. PMID- 29000417 TI - Appointments, Leave, &c. PMID- 29000418 TI - Stone in the Uterus. PMID- 29000419 TI - A Case of Very Large Calculus. PMID- 29000420 TI - Mnemonics for Intra-Cardiac Sounds. PMID- 29000421 TI - Appointments, Leave, &c. PMID- 29000422 TI - Ptomaines and Leucomaines. PMID- 29000423 TI - Simple and Complicated Ruptures of the Intestines. PMID- 29000424 TI - Medical News. PMID- 29000425 TI - Cholera and Milk. PMID- 29000427 TI - Joint Diseases Following Variola. PMID- 29000426 TI - Transactions of Medical Societies. PMID- 29000429 TI - Report of the Second Hyderabad Chloroform Commission. PMID- 29000428 TI - Current Medical Topics. PMID- 29000431 TI - Service Notes. PMID- 29000430 TI - Salol in Cholera. PMID- 29000432 TI - Transactions of Medical Societies. PMID- 29000434 TI - Report of the Second Hyderabad Chloroform Commission. PMID- 29000433 TI - A Case of Diabetes. PMID- 29000436 TI - Medical News. PMID- 29000435 TI - Vaccination and Cowpox. PMID- 29000438 TI - Case of Pendulous Fibrous Tumour of Mouth. PMID- 29000437 TI - Contributions to the Indian Materia Medica. PMID- 29000440 TI - Service Notes. PMID- 29000439 TI - Current Medical Topics. PMID- 29000442 TI - Appointments, Leave, &c. PMID- 29000441 TI - River Pollution in India. PMID- 29000443 TI - Complicated Ruptures of the Spleen. PMID- 29000445 TI - A Yunani School at Delhi. PMID- 29000444 TI - Further Experiences of the Surgery of Stone in the Bladder. PMID- 29000446 TI - Ectopic Gestation. PMID- 29000447 TI - Salol in Cholera. PMID- 29000448 TI - Salol in the Gastro-Intestinal Derangements of Children. PMID- 29000450 TI - Service Notes. PMID- 29000449 TI - Eden Hospital, Calcutta; Abdominal Surgery during the Year 1888-89. PMID- 29000451 TI - Glycerine Enemata. PMID- 29000452 TI - On the Association of Several Distinct Species of Comma-Bacilli with Cases of Cholera in Calcutta. PMID- 29000453 TI - Tolerance of Operation on the Liver. PMID- 29000454 TI - Latrine Arrangements in Calcutta Institutions. PMID- 29000456 TI - Medical News. PMID- 29000455 TI - The Salol Treatment of Cholera. PMID- 29000457 TI - Precis of Operations Performed in the Wards of the First Surgeon, Medical College Hospital, during the Year 1889. PMID- 29000459 TI - Transactions of Medical Societies. PMID- 29000458 TI - Contribution to the Practice of Midwifery. PMID- 29000460 TI - Medical and Surgical Work in Kashmir. PMID- 29000461 TI - Current Medical Topics. PMID- 29000463 TI - The Twenty-Fifth Report of the Sanitary Commissioner, with the Government of India. PMID- 29000462 TI - Change of Colour in a Cock's Feathers from Fear. PMID- 29000464 TI - Precis of Operations Performed in the Wards of the First Surgeon, Medical College Hospital, during the Year 1889. PMID- 29000465 TI - Notes on Cholera Treatment. PMID- 29000466 TI - Lord Camperdown's Committee. PMID- 29000467 TI - Rhamnus Catharticus as a Remedy for Toothache. PMID- 29000469 TI - Medical News. PMID- 29000468 TI - Transactions of Medical Societies. PMID- 29000470 TI - A Successful Ovariotomy. PMID- 29000471 TI - Influenza. PMID- 29000472 TI - Service Notes. PMID- 29000473 TI - Report of the Second Hyderabad Chloroform Commission. PMID- 29000474 TI - Epsom College. PMID- 29000475 TI - Ruptures of Internal Organs, Part VI: Simple and Complicated Ruptures of the Heart. PMID- 29000476 TI - Salol in Cholera. PMID- 29000478 TI - The Treatment of Cholera. PMID- 29000477 TI - Current Medical Topics. PMID- 29000479 TI - Rupture of the Spleen: Death Occurring 13 Days after the Injury. PMID- 29000480 TI - Rupture of the Spleen No. 2: Death 11 Days after. PMID- 29000481 TI - Transactions of Medical Societies. PMID- 29000482 TI - The Treatment of Cholera by Salol. PMID- 29000484 TI - Removal of a Very Large Tumour from the Neck. PMID- 29000483 TI - A Record of Six Months' Medico-Legal Work in the Medical College, Calcutta. PMID- 29000485 TI - Cholera Diffusion. PMID- 29000486 TI - Current Medical Topics. PMID- 29000487 TI - Service Notes. PMID- 29000488 TI - Trephining as a Means of Relieving Tension. PMID- 29000489 TI - Medical News. PMID- 29000490 TI - Carcinoma of Breast. PMID- 29000491 TI - Pneumonia-Gangrene of the Lung. Recovery. PMID- 29000492 TI - Service Notes. PMID- 29000493 TI - Transactions of Medical Societies. PMID- 29000494 TI - Recent Researches in Malarial Infection. PMID- 29000495 TI - Cause of Leprosy. PMID- 29000496 TI - Current Medical Topics. PMID- 29000497 TI - Medical News. PMID- 29000498 TI - Diphtheria and Its Relation to the Lower Animals. PMID- 29000499 TI - On the Etiology of Asiatic Cholera: A Report Furnished to the German Medical Society of Prague. PMID- 29000500 TI - Some of the Relations of the Business of the Dairy Farmer to Public Health. PMID- 29000501 TI - Vital Statistics and Sanitation. PMID- 29000502 TI - The after Treatment of Circumcision Cases. PMID- 29000503 TI - Current Medical Topics. PMID- 29000504 TI - Two Cases of Supra-Pubic Lithotomy. PMID- 29000505 TI - Gunshot Wound of Head, Causing Destruction of the Internal Ear. PMID- 29000506 TI - On the Principles of the Treatment of Diabetes Mellitus. PMID- 29000507 TI - Vesical Complications in Connection with Pelvic Affections. PMID- 29000508 TI - Leprosy in China. PMID- 29000509 TI - Hystero-Epilepsy. PMID- 29000511 TI - Friedreich's Disease. PMID- 29000510 TI - Operation on the Diabetic. PMID- 29000512 TI - Faecal Anaemia. PMID- 29000513 TI - Notes on a Visit to the Alexandra Hospital, Moscow. PMID- 29000514 TI - Medical News. PMID- 29000515 TI - Herpes Menstrualis. PMID- 29000517 TI - Service Notes. PMID- 29000516 TI - Stricture of the Rectum in a Child-Anasarca and Albuminuria. PMID- 29000518 TI - Hypertrophied Wandering Spleen with Ascites. Treatment. Recovery. PMID- 29000520 TI - Transactions of Medical Societies. PMID- 29000519 TI - Remarks on Acute Tonsillitis and Its Treatment. PMID- 29000522 TI - Pathogenic Characteristics of Microbes Found in Malignant Neoplasms. PMID- 29000521 TI - Anasarca and Albuminuria from Tight Lacing. PMID- 29000523 TI - Test for Iodoform and Iodides. PMID- 29000524 TI - Alimentary Regimen in Bright's Disease. PMID- 29000526 TI - The Fatal-After Action of Chloroform. PMID- 29000525 TI - Precis of Operations Performed in the Wards of the First Surgeon, Medical College Hospital, during the Year 1889. PMID- 29000527 TI - Appointments, Leave, &c. PMID- 29000528 TI - Bengal Jails. PMID- 29000529 TI - Porter on Famine Diseases. PMID- 29000530 TI - Service Notes. PMID- 29000531 TI - Ruptures of Internal Organs, Part VII. PMID- 29000532 TI - Forty Wounds from a Bear. PMID- 29000534 TI - On the Surgical Aspects of Impacted Labour: Extracts from Lectures to the Midwifery Class of the Medical College, Calcutta, from 1881. PMID- 29000533 TI - Clinical Lecture on Glaucoma. PMID- 29000536 TI - Medical News. PMID- 29000535 TI - Medical Education. PMID- 29000537 TI - Antiseptics. PMID- 29000539 TI - A Few Words on the Subject of Village Sanitation. PMID- 29000538 TI - Self-Mutilation-Transposition of Urethral Orifice. PMID- 29000541 TI - Syphilitic Alopecia. PMID- 29000540 TI - Letters from Drs. Maclean, Farquharson and Macnamara. PMID- 29000542 TI - The Salol Treatment of Cholera. PMID- 29000543 TI - Stone in Uterus. PMID- 29000544 TI - Very Large Malignant Tumour of Breast: Removal: Recovery. PMID- 29000545 TI - Transactions of Medical Societies. PMID- 29000546 TI - Current Medical Topics. PMID- 29000547 TI - Phenacetin as an Anti-Rheumatic. PMID- 29000548 TI - Village Sanitation in India. PMID- 29000549 TI - Medical News. PMID- 29000550 TI - Castor Oil Chocolate. PMID- 29000551 TI - Iodoform in Chronic Cystitis. PMID- 29000552 TI - Mexican Ideas Concerning the Contagiousness of Tuberculosis. PMID- 29000553 TI - Antifebrin in Quinsy. PMID- 29000554 TI - 1889. PMID- 29000556 TI - Service Notes. PMID- 29000555 TI - The Fever of Bhamo. PMID- 29000557 TI - Transactions of Medical Societies. PMID- 29000558 TI - A Case Showing the Contagiousness of Phthisis. PMID- 29000560 TI - The Relation of Dentition to Diseases of the Alimentary Tract. PMID- 29000559 TI - Further Experiences in the Surgery of Stone in the Bladder. PMID- 29000561 TI - Rhinoplastic Surgery. PMID- 29000562 TI - An Epidemic of Phthisis. PMID- 29000563 TI - Cerebral Localisation in Its Practical Relations. PMID- 29000564 TI - Malaria v. More Recognisable Causes of Disease. PMID- 29000565 TI - Small Doses of Antimony in Inflammations: Extract from a Report of the Civil Med'. Department of His Highness the Nizam's Govt. for 1888 (1297 Fasli). PMID- 29000567 TI - The Treatment of Obesity. PMID- 29000566 TI - Codeine in Diabetes. PMID- 29000569 TI - Phenacetin. PMID- 29000568 TI - Current Medical Topics. PMID- 29000570 TI - Experiences of a Beginner in Litholapaxy. PMID- 29000571 TI - Notes on Two Fatal Cases of Gunshot Wound. PMID- 29000572 TI - Precis of Operations Performed in the Wards of the First Surgeon, Medical College Hospital, during the Year 1890. PMID- 29000573 TI - Current Medical Topics. PMID- 29000574 TI - Tar Ointment in Chronic Eczema. PMID- 29000576 TI - Service Notes. PMID- 29000575 TI - Ague or Intermittent Fever. PMID- 29000577 TI - Medical News. PMID- 29000578 TI - The International Congress of Hygiene and Demography. PMID- 29000579 TI - A Case of Hydrophobia Cured by Subcutaneous Injection of Hydrochlorate of Pilocarpine. PMID- 29000580 TI - Case of Foreign Body in Male Bladder Removed by Lithotomy. PMID- 29000581 TI - The Treatment of Hernia by Median Abdominal Section. PMID- 29000583 TI - Transactions of Medical Societies. PMID- 29000582 TI - Surgical Notes from the Black Mountain. PMID- 29000584 TI - Vital Events of 1889. PMID- 29000585 TI - The Hurdwar Kumbh of 1891. PMID- 29000587 TI - Dangers of Catheterization. PMID- 29000588 TI - Is Colonization in Central Africa by Europeans Practicable. PMID- 29000586 TI - A Case of Catheter Fever Followed by Suppression of Urine and Death. PMID- 29000589 TI - Service Notes. PMID- 29000590 TI - A Case of Splenectomy. PMID- 29000591 TI - Current Medical Topics. PMID- 29000592 TI - The Treatment of the Sac. PMID- 29000593 TI - Opium Suicides in the Hurdoi District. PMID- 29000594 TI - Medical News. PMID- 29000595 TI - A Case of Uraemicpoisoning-Recovery. PMID- 29000596 TI - Precis of Operations Performed in the Wards of the First Surgeon, Medical College Hospital, during the Year 1890. PMID- 29000597 TI - Appointments, Leave, &c. PMID- 29000598 TI - Cases of Hysteria. PMID- 29000600 TI - Service Notes. PMID- 29000599 TI - A Preliminiary Note on the Nature and Pathology of the Disease Known as "Surra," Affecting Horses and Mules in India. PMID- 29000602 TI - Medical News. PMID- 29000601 TI - Transactions of Medical Societies. PMID- 29000604 TI - Phagocytes. PMID- 29000603 TI - Notes of a Case of Large Fatty Tumour Removed at the Arrah Hospital. PMID- 29000605 TI - On Recruiting the Anglo-Indian Army. PMID- 29000606 TI - Notes on Cocaine Operations. PMID- 29000607 TI - Cases of Foreign Body. PMID- 29000608 TI - The Treatment of the Morphine Disease. PMID- 29000609 TI - Case of Aneurism of the Arch of the Aorta. PMID- 29000610 TI - Current Medical Topics. PMID- 29000611 TI - Microscopical Society of Calcutta. PMID- 29000612 TI - What Changes Take Place in the Lower Portion of a Scrotal Hernial Sac after Ligature and Division of Its Neck. PMID- 29000614 TI - Transactions of Medical Societies. PMID- 29000613 TI - Pneumonia. PMID- 29000615 TI - Note on the Bad Effects of Poultices for Spreading Ulcers. PMID- 29000616 TI - Successful Case of Ovariotomy. PMID- 29000618 TI - Current Medical Topics. PMID- 29000619 TI - Koch's Remedy and Homoeopathy. PMID- 29000617 TI - Note on Arsenic as a Prophylactic for Malaria. PMID- 29000621 TI - Medical News. PMID- 29000622 TI - Virchow on Koch's Treatment of Tubercle. PMID- 29000620 TI - Appointments, Leave, &c. PMID- 29000623 TI - Plastic Operation on the Face for Bite from a Bear. PMID- 29000624 TI - Case of Myxo-Sarcoma. PMID- 29000625 TI - Service Notes. PMID- 29000626 TI - Treatment of Diphtheria. PMID- 29000627 TI - A Case of Concussion of the Spine. PMID- 29000628 TI - Cocaine in Asthma. PMID- 29000629 TI - The Treatment of the Morphine-Disease. PMID- 29000630 TI - On Carlsbad Treatment for Anglo-Indians. PMID- 29000631 TI - A Further Communication on a Remedy for Tuberculosis. PMID- 29000632 TI - Burdwan Dispensary: Death from Chloroform. PMID- 29000633 TI - Pilgrims and Cholera. PMID- 29000634 TI - A Form of Ulcerative Gingivitis Common to Men and Dogs in India. PMID- 29000635 TI - A Case of Acute Ectropium of Both Eyes Ending in Disorganization of Both Eyeballs. PMID- 29000638 TI - Henry Jacob Bigelow. PMID- 29000637 TI - Tenacity of Vitality in Larvae and Low Forms of Organic Life. PMID- 29000636 TI - Transactions of Medical Societies. PMID- 29000639 TI - Current Medical Topics. PMID- 29000640 TI - Service Notes. PMID- 29000641 TI - Malarial Analogies. PMID- 29000643 TI - The Disinfecting Value of Sulphur Dioxide. PMID- 29000642 TI - Case of Foreign Body in the Stomach. PMID- 29000644 TI - Compound Fractures Treated by Creolin Irrigation. PMID- 29000645 TI - Case of Porro's Operation. PMID- 29000646 TI - Notes of a Case of Aural Vertigo Following an Injury to the Head. PMID- 29000647 TI - Clinical Studies of Disease as Observed in China. PMID- 29000648 TI - For the Relief of Earache. PMID- 29000649 TI - Compound Fracture of Skull: Sudden Death without Brain Symptoms. PMID- 29000650 TI - Medical News. PMID- 29000651 TI - Prophylaxis in Malarial Fevers. PMID- 29000652 TI - Significance of Difference between Two Radial Pulses. PMID- 29000653 TI - A Case of Compound Comminuted Fracture of the Vertex of the Skull under the Care of Surgeon-Major R. Macrae, M.B. PMID- 29000655 TI - Current Medical Topics. PMID- 29000656 TI - Untoward Effects of Exalgine. PMID- 29000654 TI - Notes of Two Cases of Cerebro-Spinal Fever, Rungpore Jail. PMID- 29000658 TI - What Is the Rational Treatment of Acute Dysentery? PMID- 29000657 TI - Treatment of Syphilis by Hypodermic Injections of Corrosive Sublimate. PMID- 29000659 TI - Cases of Glaucoma. PMID- 29000660 TI - Precis of Operations Performed in the Wards of the First Surgeon, Med. Coll. Hospital. PMID- 29000661 TI - Angina Pectoris with Post-Mortem Examination. Fatty Degeneration of Heart. PMID- 29000663 TI - Case of Chorea with Pregnancy. PMID- 29000662 TI - Case of Foreign Body in the Bladder. PMID- 29000664 TI - Medical News. PMID- 29000665 TI - Recovery of the Snake-Bite. PMID- 29000666 TI - Transactions of Medical Societies. PMID- 29000668 TI - Service Notes. PMID- 29000667 TI - Ehrlich's Test in Typhoid Fever. PMID- 29000669 TI - The Inoculability of Malignant Growths. PMID- 29000670 TI - Life History of the Haematozoon of Malaria. PMID- 29000671 TI - Case of Leprosy. Unna's Treatment-No Benefit. PMID- 29000672 TI - Electricity in the Treatment of Disease. PMID- 29000673 TI - Professor Koch's Discovery. PMID- 29000674 TI - Notes on Hill Malaria. PMID- 29000675 TI - Pneumonia. PMID- 29000676 TI - Vaginal Atresia. PMID- 29000677 TI - Fissure of the Anus and Masturbation. PMID- 29000679 TI - Current Medical Topics. PMID- 29000678 TI - Contagiosity of Tuberculosis. PMID- 29000680 TI - Treatment of Diphtheria by Inoculation. PMID- 29000681 TI - Traumatic Stricture: Wheelhouse: Failure. PMID- 29000682 TI - Transactions of Medical Societies. PMID- 29000683 TI - Abscess of the Lung-Peribronchial. PMID- 29000684 TI - A Further Communication on a Remedy for Tuberculosis: Translated from the Original Article Published in the "Deutsche Medicinische Wochenschrift," and Published as a Special Supplement to the "British Medical Journal" of November 15th. PMID- 29000685 TI - Tumour on a Nerve. PMID- 29000687 TI - 1890. PMID- 29000686 TI - Mental Depression, Hallucinations and Delusions Associated with Ischio - Rectal Abscess. PMID- 29000688 TI - Medical News. PMID- 29000689 TI - Appointments, Leave, &c. PMID- 29000691 TI - Current Medical Topics. PMID- 29000690 TI - Service Notes. PMID- 29000692 TI - Precis of Operations Performed in the Wards of the First Surgeon, Medical College Hospital, during the Year 1890. PMID- 29000693 TI - Transactions of Medical Societies. PMID- 29000694 TI - Appointments, Leave, &c. PMID- 29000695 TI - Two Cases Bearing on the Treatment in an Early Stage of Filarial Disease of the Lymphatics. PMID- 29000696 TI - Service Notes. PMID- 29000697 TI - Medical News. PMID- 29000698 TI - Basu on the Study of Indigenous Drugs. PMID- 29000699 TI - A Case of Acute Malarial Poisoning, Enteric Fever Ensuing. Complicated by Brain and Lung Symptoms, Also by Extensive Cancrum Oris. PMID- 29000700 TI - Resection of a Rib for Abscess of Right Lung-Recovery. PMID- 29000701 TI - Immunity. PMID- 29000702 TI - Arthrectomy. PMID- 29000703 TI - Remarks on the Therapeutic Uses and Effects of Antipyrin. PMID- 29000704 TI - Notes of a Case of Dysidrosis: Syn.-Chiro-Pompholyx, Hydro-Adenitis. PMID- 29000706 TI - The Treatment of Hydrocele by Incision. PMID- 29000705 TI - For Painful Haemorrhoids. PMID- 29000707 TI - Concussion of the Lungs and Pneumonia. PMID- 29000708 TI - Dysentery and Its Treatment. PMID- 29000709 TI - On the Medico-Legal Detection of Human Blood. PMID- 29000710 TI - Enchoudroma of the Lower Jaw-Excision-Recovery. PMID- 29000711 TI - Current Medical Topics. PMID- 29000712 TI - Appointments, Leave, &c. PMID- 29000713 TI - Erratum. AB - [This corrects the article on p. 176 in vol. 26.]. PMID- 29000714 TI - The Eliminative Treatment of Puerperal Septicaemia. PMID- 29000716 TI - Malarial Fevers. PMID- 29000715 TI - Transposition of Viscera. PMID- 29000717 TI - Wholesale Poisoning at a Wedding Feast. PMID- 29000718 TI - Coffee as a Germicide. PMID- 29000720 TI - Medical News. PMID- 29000719 TI - Multiple Injuries: Compound Comminuted Fracture of the Neck of the Scapula (Including the Entire Glemoid Cavity) and of the Acromion and Coracoid Processes Poisoned Wounds-Recovery. PMID- 29000722 TI - Transactions of Medical Societies. PMID- 29000721 TI - On the Study of Indigenous Drugs. PMID- 29000723 TI - Service Notes. PMID- 29000724 TI - Precis of Operations Performed in the Wards of the First Surgeon, Medical College Hospital, during the Year 1890. PMID- 29000725 TI - Typhoid Fever. PMID- 29000726 TI - Tuberculosis in Cattle. PMID- 29000727 TI - Recovery of Animals Attacked with Rabies. PMID- 29000728 TI - Service Notes. PMID- 29000729 TI - The Calcutta Medical College. PMID- 29000730 TI - Transactions of Medical Societies. PMID- 29000731 TI - A Case of Ovarian Tumour. PMID- 29000732 TI - Large Abscess of Spleen. PMID- 29000733 TI - Precis of Operations Performed in the Wards of the First Surgeon, Medical College Hospital. PMID- 29000734 TI - Cases of Obstructed Labour. PMID- 29000735 TI - Winter Practice in Kashmir. PMID- 29000737 TI - Medical News. PMID- 29000736 TI - Village Sanitation. PMID- 29000739 TI - Cases of Vesical Calculus. PMID- 29000738 TI - The Treatment of Carbuncle. PMID- 29000740 TI - Kala-Azar in Assam. PMID- 29000741 TI - Contributions to the Practice of Midwifery. PMID- 29000742 TI - Fatal Injury by a Stick Thrust into the Rectum. PMID- 29000744 TI - Current Medical Topics. PMID- 29000743 TI - Operations for Hernia. PMID- 29000745 TI - A Case of Hydrophobia Caused by Squirrel-Bite. PMID- 29000746 TI - Malarial Fevers. PMID- 29000747 TI - Appointments, Leave, &c. PMID- 29000748 TI - Rudolf Virchow. PMID- 29000749 TI - Maritime Quarantine and Indian Cholera. PMID- 29000751 TI - A Case of Peculiar Paralysis. PMID- 29000750 TI - Case of Snake-Bite. PMID- 29000753 TI - Medical News. PMID- 29000752 TI - Case of Persistent Hyaloid Artery. PMID- 29000754 TI - Service Notes. PMID- 29000756 TI - Maritime Quarantine and Sanitation in Relation to Cholera. PMID- 29000755 TI - Antipyrin and Sp. Eth. Nitrosi. PMID- 29000758 TI - Prevalence of Bowel-Complaints in Prisons. PMID- 29000757 TI - Vital Statistics and Sanitation. PMID- 29000759 TI - Case of Chyluria Treated with Gallic Acid and Thymol. PMID- 29000761 TI - Current Medical Topics. PMID- 29000760 TI - Two Cases of Large Uterine Polypus. PMID- 29000762 TI - Transactions of Medical Societies. PMID- 29000763 TI - Ainhum and Polydactylism. PMID- 29000765 TI - Medical News. PMID- 29000764 TI - A Case of Vesical Calculus with Peculiar Complications. PMID- 29000767 TI - Koch on Cholera in Calcutta. PMID- 29000766 TI - Appointments, Leave, &c. PMID- 29000769 TI - Service Notes. PMID- 29000768 TI - Three Cases of Strangulation. PMID- 29000770 TI - Remittent and Enteric Fever. PMID- 29000772 TI - Poisonous Holds and Store-Rooms. PMID- 29000771 TI - Short Notes of Cases of Pernicious Anaemia (Presumed Addison's Disease.). PMID- 29000773 TI - Current Medical Topics. PMID- 29000774 TI - Diagnosis of Insanity. PMID- 29000775 TI - Precis of Operations Performed in the Wards of First Surgeon, Medical College Hospital, during the Year 1887. PMID- 29000777 TI - Transactions of Medical Societies. PMID- 29000776 TI - Recent Experiences in the Treatment of Stone in the Bladder. PMID- 29000778 TI - Typhoid and Remittent Fever. PMID- 29000779 TI - Precis of Operations Performed in the Wards of the 1st Surgeon, Medical College Hospital, during the Year 1887. PMID- 29000780 TI - Local Sweating in the Armpits. PMID- 29000781 TI - Current Medical Topics. PMID- 29000782 TI - Traumatic Aneurism in a Child under One Year. PMID- 29000783 TI - Remarks on the Significance of Albuminuria and Glycosuria in Native Patients. PMID- 29000784 TI - Transactions of Medical Societies. PMID- 29000785 TI - Polypus of the Uterus. PMID- 29000786 TI - Sulphide of Calcium. PMID- 29000787 TI - Service Notes. PMID- 29000788 TI - The Radical Cure of Hernia. PMID- 29000789 TI - A Note on the Climate of Hill Stations in Southern India. PMID- 29000791 TI - Hill Diarrhoea. PMID- 29000790 TI - A Case of Dyspepsia Attended with Severe Spasms of the Diaphragm, Duration Three Months, Cured within a Week. PMID- 29000792 TI - Medical News. PMID- 29000793 TI - Rabic Virus and Hydrophobia. PMID- 29000795 TI - Stones in the Uterus. PMID- 29000794 TI - Enteric Fever in India. PMID- 29000796 TI - Indian Sprue. PMID- 29000798 TI - Cholera and Its Treatment. PMID- 29000797 TI - Feeding after Excision of Tongue. PMID- 29000800 TI - Disease of the Suprarenal Capsules, or Pernicious Anaemia. PMID- 29000799 TI - Appointments, Leave, &c. PMID- 29000802 TI - Service Notes. PMID- 29000801 TI - An Interesting Case of Hysteria in a Boy. PMID- 29000803 TI - The Lewis Memorial. PMID- 29000805 TI - Criminal Lunatics. PMID- 29000804 TI - Case of Spurious Hermaphroditism. PMID- 29000807 TI - Medical News. PMID- 29000806 TI - Recent Experiences in the Treatment of Stone in the Bladder. PMID- 29000808 TI - Report on the Outbreak of Cholera in the Remount Depot at Babooghur in 1887. PMID- 29000810 TI - A Case of Urethral Calculus. PMID- 29000809 TI - Two Cases of Fracture of Spine. PMID- 29000812 TI - Notes on Cataract and Other Operations on the Eyeball. PMID- 29000811 TI - Notes on the Evolution of Disease. PMID- 29000813 TI - Gunshot Wound Followed by Pulmonary Embolism and Cardiac Thrombosis. PMID- 29000814 TI - Transactions of Medical Societies. PMID- 29000815 TI - Cocaine in the Surgical Treatment of Hydrocele. PMID- 29000816 TI - Current Medical Topics. PMID- 29000817 TI - Short Notes on 130 Cases of Hanging. PMID- 29000818 TI - A Note on the Usefulness of Naoshadar or Sal Ammoniac. PMID- 29000819 TI - Current Medical Topics. PMID- 29000821 TI - An Obscure Skin Disease. PMID- 29000820 TI - Cases of Rhinoplasty. PMID- 29000822 TI - On Cholera. PMID- 29000824 TI - Fish Poisoning. PMID- 29000823 TI - Extract. PMID- 29000826 TI - Transactions of Medical Societies. PMID- 29000825 TI - A Sketch of the Medical and Surgical Experiences of the War of the Rebellion in America, during the Years 1861-65. PMID- 29000828 TI - Service Notes. PMID- 29000827 TI - Milk and Water. PMID- 29000829 TI - Cases of Enteric Fever in Calcutta. PMID- 29000830 TI - The Twenty-Third Annual Report of the Sanitary Commissioner with the Government of India. PMID- 29000831 TI - Appointments, Leave, &c. PMID- 29000832 TI - Medical News. PMID- 29000833 TI - Transactions of Medical Societies. PMID- 29000834 TI - Conservative Dentistry versus Tooth Extraction. PMID- 29000835 TI - Service Notes. PMID- 29000836 TI - Current Medical Topics. PMID- 29000838 TI - Netley. PMID- 29000837 TI - A Case of Empyema Following on Remittent Fever. PMID- 29000839 TI - A Sketch of the Medical and Surgical Experiences of the War of the Rebellion in America during the Years 1861-65. PMID- 29000841 TI - Medical News. PMID- 29000840 TI - Purpura Haemorrhagica Occurring during the Course of Pneumonia. PMID- 29000843 TI - Sanitation in India. PMID- 29000842 TI - The Action of Antipyrin on the Vaso-Motor System. PMID- 29000844 TI - Recent Experiences in the Treatment of Stone in the Bladder. PMID- 29000845 TI - Short Notes of Cases of Pernicious Anaemia. PMID- 29000846 TI - The Treatment of Dracunculus by Amarpatee. PMID- 29000847 TI - Hepatic Disease in Young Children. PMID- 29000848 TI - A Sketch of the Medical and Surgical Experiences of the War of the Rebellion in America, during the Years 1861-65. PMID- 29000849 TI - Aconite Treatment in Acute Dysentery. PMID- 29000850 TI - Cases of Rhinoplasty. PMID- 29000852 TI - Service Notes. PMID- 29000851 TI - A Stretcher. PMID- 29000854 TI - Purpura Rheumatica et Haemorrhagica. PMID- 29000853 TI - Contributions to the Indian Materia Medica-On the Medical Properties of Some of the Indigenous Plants of Southern India. PMID- 29000855 TI - Medical News. PMID- 29000857 TI - The Logic of Quackery. PMID- 29000856 TI - Current Medical Topics. PMID- 29000859 TI - Transactions of Medical Societies. PMID- 29000858 TI - Case of Occlusion of the Mouth of the Right Coronary Artery in the Course of General Atheroma, with Aneurismal Dilitation of the Arch of the Aorta. PMID- 29000860 TI - Dentists and Medical Men. PMID- 29000861 TI - The Twenty-Third Annual Report of the Sanitary Commissioner with the Government of India. PMID- 29000862 TI - Appointments, Leave, &c. PMID- 29000863 TI - Spleen Pills. PMID- 29000865 TI - Appointments, Leave, &c. PMID- 29000864 TI - Notes on Abortive Typhoid. PMID- 29000866 TI - Pasteurism. PMID- 29000867 TI - A Successful Case of Supra Pubic Lithotomy. PMID- 29000868 TI - Notes on Litholapaxy with Special Reference to the Operation as Performed on Male Children. PMID- 29000870 TI - Dissolution and Evolution and the Science of Medicine. PMID- 29000869 TI - Notes on the Evolution of Disease. PMID- 29000871 TI - Service Notes. PMID- 29000872 TI - On the Treatment of Carbuncle by Scraping. PMID- 29000874 TI - Medical News. PMID- 29000873 TI - Miss Anna Williams. PMID- 29000875 TI - Eserine in Night-Blindness. PMID- 29000877 TI - Current Medical Topics. PMID- 29000876 TI - A Query. PMID- 29000878 TI - Transactions of Medical Societies. PMID- 29000879 TI - Medical News. PMID- 29000880 TI - On Cholera. PMID- 29000881 TI - Precis of Operations Performed in the Wards of the 1st Surgeon, Medical College Hospital, during the Year 1887. PMID- 29000882 TI - Cases of Rhinoplasty. PMID- 29000884 TI - The Physical Concomitants of Malaria. PMID- 29000883 TI - Strange Course of a Bullet. PMID- 29000885 TI - Appointments, Leave, &c. PMID- 29000886 TI - Current Medical Topics. PMID- 29000887 TI - Service Notes. PMID- 29000888 TI - A Sketch of the Medical and Surgical Experiences of the War of the Rebellion in America during the Years 1861-65. PMID- 29000890 TI - Case of Transverse Presentation. PMID- 29000891 TI - The Twenty-Third Annual Report of the Sanitary Commissioner with the Government of India. PMID- 29000889 TI - Aconite Treatment in Acute Dysentery. PMID- 29000892 TI - A Sketch of the Medical and Surgical Experiences of the War of the Rebellion in America, during the Years 1861-65. PMID- 29000893 TI - A Medical Revival in Egypt. PMID- 29000895 TI - Medical News. PMID- 29000894 TI - Precis of Operations Performed in the Wards of the 1st Surgeon, Medical College Hospital, during the Year 1887. PMID- 29000896 TI - On Cholera. PMID- 29000897 TI - Modern Antipyretics in Remittent Fever. PMID- 29000898 TI - A Case of Venomous Bite by Echis Carinata. PMID- 29000899 TI - Changing Your Doctor. PMID- 29000900 TI - Current Medical Topics. PMID- 29000902 TI - Case of Foreign Body in the Windpipe. PMID- 29000901 TI - Service Notes. PMID- 29000903 TI - Cases of Rhinoplasty. PMID- 29000904 TI - Transactions of Medical Societies. PMID- 29000905 TI - Pancreatic Diabetes. PMID- 29000906 TI - Remittent and Enteric Fever. PMID- 29000908 TI - Notes on Litholapaxy, with Special Reference to the Operation as Performed on Male Children. PMID- 29000907 TI - Cases Illustrating the Diverse Appearances Found on Postmortem Examination of the Drowned. PMID- 29000909 TI - Current Medical Topics. PMID- 29000910 TI - Service Notes. PMID- 29000911 TI - Medical News. PMID- 29000913 TI - Medical Education of Women in Rajputana. PMID- 29000912 TI - Transactions of Medical Societies. PMID- 29000914 TI - The Anchylostomum Duodenale: Its Wide Prevalence, and Connection with Jail Debility. PMID- 29000916 TI - Rigor Mortis. PMID- 29000915 TI - The National Association for Supplying Female Medical Aid to the Women of India. PMID- 29000918 TI - Fancy Fees. PMID- 29000917 TI - Enteric Fever in India. PMID- 29000920 TI - Dispensaries of the N.-W. Provinces and Oudh. PMID- 29000919 TI - Case of Rodent Ulcer. PMID- 29000921 TI - An Interesting Case of Insolation in the Jhang Jail. PMID- 29000922 TI - On Cholera. PMID- 29000924 TI - The Diagnosis of Tropical Enteric Fever. PMID- 29000923 TI - The Causation of Cholera. PMID- 29000926 TI - Fish Poisoning. PMID- 29000925 TI - Gonorrhoea as Seen in the Army. PMID- 29000928 TI - Tumour of the Supra-Orbital Region. PMID- 29000927 TI - Appointments, Leave, &c. PMID- 29000929 TI - Hepatic Cirrhosis in Children. PMID- 29000930 TI - Fees for Medical Reports for Life Assurance. PMID- 29000931 TI - Tumour Simulating Spina Bifida. PMID- 29000932 TI - Re-Fracture and Re-Setting of Bones. PMID- 29000933 TI - Case of Mania in a Child. PMID- 29000935 TI - Transactions of Medical Societies. PMID- 29000934 TI - Service Notes. PMID- 29000936 TI - Current Medical Topics. PMID- 29000937 TI - Medical News. PMID- 29000938 TI - Erratum. AB - [This corrects the article on p. 322 in vol. 23.]. PMID- 29000939 TI - Medical News. PMID- 29000941 TI - Service Notes. PMID- 29000940 TI - Surgical Work in the State Hospital of Kashmere. PMID- 29000943 TI - Current Medical Topics. PMID- 29000942 TI - Remakrs on Fever Mortality at Deobund in 1884. PMID- 29000944 TI - Transactions of Medical Societies. PMID- 29000945 TI - Remedies for Uterine Haemorrhage. PMID- 29000947 TI - Appointments, Leave, &c. PMID- 29000946 TI - Hospital Bed for the Helpless and Injured. PMID- 29000949 TI - Treatment of Constipation by Faradism. PMID- 29000948 TI - 1887. PMID- 29000950 TI - Dr. Francis on the Variolation of Cows. PMID- 29000951 TI - Some Interesting and Peculiar Cases at Poonamalee, Madras, from 1883 to 1885. PMID- 29000952 TI - Two Successful Cases of Ovariotomy. PMID- 29000953 TI - A Note on the Treatment of Mammary Sinus by Extract of Belladonna. PMID- 29000954 TI - Medico-Legal Work in the District of Backergunge from January to June 1892. PMID- 29000955 TI - Archibald Hamilton Hilson, M.D. PMID- 29000957 TI - Chloroform. PMID- 29000956 TI - Select Cases from the Santosh Golokenath Dispensary. PMID- 29000959 TI - Transactions of Medical Societies. PMID- 29000958 TI - Pathological and Etiological Relations of Tropical Suppurative Hepatitis. PMID- 29000961 TI - Memoranda on Water Filtration by the Chamberland-Pasteur and Nordtmeyer-Berk Feld Systems (Illustrated). PMID- 29000960 TI - India in 1892. PMID- 29000962 TI - The Comma Bacillus and Immunity against Cholera. PMID- 29000963 TI - Proposed Registration of Still-Born Children. PMID- 29000964 TI - Liver Abscess-Incision-Drainage-Recovery. PMID- 29000965 TI - Appointments, Promotions, Retirement, Leave, Language. PMID- 29000966 TI - Indian Fevers. PMID- 29000967 TI - Notes Regarding the Prevalence of the Dochmius Duodenalis. PMID- 29000968 TI - Vaccine Lymph-Its Origin and Cultivation. PMID- 29000969 TI - The Chest Measurement of Recruits. PMID- 29000970 TI - A Protest. PMID- 29000971 TI - Neglect of Children's Teeth. PMID- 29000972 TI - The Revival of Symphysiotomy. PMID- 29000974 TI - Chloroform Administration. PMID- 29000973 TI - The Evolution of Antiseptic Surgery: A Retrospect. PMID- 29000975 TI - Neglect of Children's Teeth. PMID- 29000976 TI - Vital Statistics and Sanitation. PMID- 29000977 TI - Appointments, Leave, Transfers. PMID- 29000978 TI - Treatment of Chronic Dysentry. PMID- 29000979 TI - The Hyderabad Chloroform Commissions. PMID- 29000980 TI - The White Man's Grave. PMID- 29000981 TI - Medical News. PMID- 29000982 TI - Current Medical Literature. PMID- 29000983 TI - The Etiological Relations of Hepatic Abscess. PMID- 29000985 TI - Transactions of Medical Societies. PMID- 29000984 TI - Peculiar Symptoms in an Infant Due to Contracted Prepuce. PMID- 29000986 TI - Large Hepatic Abscess Bursting into the Peritoneum: Laparotomy. PMID- 29000987 TI - A Resume of Some of the More Important Facts Relating to Indian Cholera. PMID- 29000988 TI - Some Remarks on the Value of Ehrlich's Test for Typhoid Fever. PMID- 29000990 TI - Etiological and Clinical Studies in Malaria. PMID- 29000989 TI - Ovarian Tumour: Operation-Death. PMID- 29000992 TI - The Anti-Cholera Vaccination: An Experimental Critique. (Read before the Pathological Society of London). PMID- 29000991 TI - Current Medical Literature. PMID- 29000994 TI - Appointments, Leave, Transfers, Promotions, Languages, Retirements. PMID- 29000993 TI - Klein's Critique Criticised. PMID- 29000995 TI - Vital Statistics and Sanitation. PMID- 29000997 TI - Proliferous Ovarian Cystic Tumour of 2 1/2 Years' Growth: Removal. PMID- 29000996 TI - Rhinoceros' Urine in Hindu Medicine. PMID- 29000998 TI - Aneurism of Right Common Carotid Artery. PMID- 29001000 TI - Vaccination in Bengal. PMID- 29000999 TI - A Resume of Some of the More Important Facts Relating to Indian Cholera. PMID- 29001002 TI - Medical News. PMID- 29001001 TI - Epidemic Infectious Pneumonia. PMID- 29001003 TI - The Hyderabad Chloroform Commissions. PMID- 29001005 TI - Transactions of Medical Societies. PMID- 29001004 TI - Case of Unusual Foreign Body in the Eye. PMID- 29001006 TI - The Cholera Epidemic of 1892. PMID- 29001007 TI - Transactions of Medical Societies. PMID- 29001008 TI - Note on a Curious Condition of Enlarged Spleen. PMID- 29001009 TI - Report of a Case of Inoculation with Carbolized Anti-Choleraic Vaccine (Haffkine). PMID- 29001010 TI - Chest Measurement of Recruits. PMID- 29001012 TI - Spread of Cholera Organisms by the Agency of Flies. PMID- 29001011 TI - Anti-Choleraic Vaccination. PMID- 29001013 TI - The Hyderabad Chloroform Commissions. PMID- 29001014 TI - The Specific Gravity of the Urine in Diabetes Mellitus. PMID- 29001016 TI - A Bacteriological Study of Drinking Water. PMID- 29001015 TI - Etiological and Clinical Studies in Malaria. PMID- 29001017 TI - Vaccination against Asiatic Cholera. PMID- 29001019 TI - Appointments. PMID- 29001018 TI - The Immorality of Over-Work. PMID- 29001021 TI - Cases from Chingleput District. PMID- 29001020 TI - Prevesical Abscess. PMID- 29001023 TI - Medical News. PMID- 29001022 TI - Cases of Dysentery Treated with Ipecacuanha Sine Emetina (Merck). PMID- 29001024 TI - India and the Contagious Diseases Act. PMID- 29001025 TI - The Evolution of Antiseptic Surgery: A Retrospect. PMID- 29001026 TI - Current Medical Literature. PMID- 29001027 TI - On the Etiology and Classification of Abscesses in the Liver. PMID- 29001028 TI - Epidemic Dropsy. PMID- 29001029 TI - Transactions of Medical Societies. PMID- 29001030 TI - Remarks on Some Recent Researches in Malaria. PMID- 29001032 TI - Criminal Poisoning. PMID- 29001031 TI - Animal Vaccine: Its Origin and Cultivation. PMID- 29001033 TI - Chest Measurement. PMID- 29001035 TI - Cases from Imambarrah Hospital, Hughli, under Surg.-Lt.-Col. K. P. Gupta, M.B., F.R.C.S. PMID- 29001034 TI - Facts about Whiskey. PMID- 29001036 TI - A Case of Beri Beri. PMID- 29001037 TI - Appointments, Leave, &c. PMID- 29001038 TI - Medical News. PMID- 29001039 TI - Jail Notes. PMID- 29001040 TI - Snake-Bite Cases. PMID- 29001041 TI - Appointments, &c. PMID- 29001042 TI - Asthma and Its Analogues. PMID- 29001044 TI - London Letter. PMID- 29001043 TI - Horse Surra. PMID- 29001045 TI - Intermittent Child-Crying and Malaria. PMID- 29001046 TI - Cases from the Imambarrah Hospital in Hughli. PMID- 29001047 TI - Correspondence. PMID- 29001048 TI - Medical Professorships in India. PMID- 29001049 TI - Current Medical Literature. PMID- 29001050 TI - Pilgrims and Mecca. PMID- 29001051 TI - Transactions of Medical Societies. PMID- 29001052 TI - Sanitation, &c. PMID- 29001053 TI - A Supposed Rare Symptom in Malaria. PMID- 29001054 TI - On Microbes in Soda-Water. PMID- 29001055 TI - Medical News. PMID- 29001056 TI - Coloured Spectacles. PMID- 29001057 TI - A Case of Enteric Fever in a Gurkha-Intestinal Haemorrhage: Death. PMID- 29001058 TI - Hindu System of Medicine. PMID- 29001059 TI - Sanitary Administration in India. PMID- 29001060 TI - Etiology of Tropical Liver Abscess. PMID- 29001061 TI - A Modified Operation for Extraction of Senile Cataract. PMID- 29001062 TI - On the Use of Methylene Blue in Malarial Fevers. PMID- 29001063 TI - Boiled Water for Troops &c. PMID- 29001064 TI - Diurnal Vomiting. PMID- 29001065 TI - Strychnine as an Antidote to Snake-Poison. PMID- 29001066 TI - On a Symptom Specially Diagnostic of Guinea-Worm in Central India. PMID- 29001067 TI - Extraction of Senile Cataract. PMID- 29001068 TI - Vital Statistics and Sanitation. PMID- 29001069 TI - Matinal (Hill) Diarrhoea. PMID- 29001070 TI - Malignant Remittent Fever at Peshawar. PMID- 29001071 TI - Unna's Treatment of Leprosy. A Paper Read before the Bombay Branch of the British Medical Association. PMID- 29001072 TI - Excision of Scrofulous Glands of the Neck. PMID- 29001073 TI - Pathological and Etiological Relations of Tropical Suppurative Hepatitis. PMID- 29001074 TI - Transactions of Medical Societies. PMID- 29001076 TI - An Important Possibility Regarding the Haematozoon Malariae. PMID- 29001075 TI - The Chest-Measurement of Recruits. PMID- 29001077 TI - Vicarious Haemorrhage. PMID- 29001079 TI - 1892. PMID- 29001078 TI - Mad Animal's Bite. PMID- 29001081 TI - The Customs Department of Bengal, 1891-92. PMID- 29001080 TI - Notes Regarding the Prevalence of the Dochmius Duodenalis. PMID- 29001082 TI - A Case of Unilateral Loss of Taste, the Result of an Injury to the Ear. PMID- 29001084 TI - Diarrhoea Alba. PMID- 29001083 TI - Indian Fevers. PMID- 29001086 TI - Typhus Fever in the Khojak Pass. PMID- 29001085 TI - Appointments, Promotions, Retirement, Resignation, Leave, Language. PMID- 29001088 TI - The Curability of Cancer by Erysipelas. PMID- 29001089 TI - Undescended Testis with Hydrocele Totalis Communicans. PMID- 29001087 TI - Two Cases of Perforation of Intestine. PMID- 29001091 TI - London Letter. PMID- 29001090 TI - Frequency of Stone in Children and Absence in Adults. PMID- 29001092 TI - A Case of Tumour: Innocent but Remarkable for Size and Appearance. PMID- 29001093 TI - Medical News. PMID- 29001094 TI - Current Medical Literature. PMID- 29001096 TI - Report of the Leprosy Commission in India. PMID- 29001095 TI - A Case of Snake-Bite Treated by Hypodermic Injection of Sulphate of Strychnia: Recovery. PMID- 29001097 TI - Transactions of Medical Societies. PMID- 29001098 TI - Further Notes on the Prevalence of the Dochmius Duodenalis. PMID- 29001100 TI - The Evolution of Antiseptic Surgery: A Retrospect. PMID- 29001099 TI - Appointments, Leave, &c. PMID- 29001101 TI - Peculiar Symptoms in an Infant Due to Contracted Prepuce. PMID- 29001103 TI - Case of Urethral Calculus. PMID- 29001102 TI - Epidemic Dropsy. PMID- 29001104 TI - Treatment of Cholera by Irrigation of the Bowel. PMID- 29001105 TI - Headache. PMID- 29001106 TI - Notes Regarding the Prevalence of the Dochmius Duodenalis. PMID- 29001107 TI - Proposed Registration of Still-Born Children. PMID- 29001108 TI - Transactions of Medical Societies. PMID- 29001110 TI - On the Use of Chloride of Calcium in the Treatment of Pneumonia. PMID- 29001109 TI - Cases from Chingleput District. PMID- 29001111 TI - Cases from Barisal Municipal Hospital. PMID- 29001112 TI - Cases of Malarial Neuroretinitis. PMID- 29001113 TI - Pathological and Etiological Relations of Tropical Suppurative Hepatitis. PMID- 29001114 TI - Malarial Fevers. Geo. Ranking. PMID- 29001115 TI - Cholera in Europe and India. PMID- 29001117 TI - Ophthalmic Surgery, 1892. PMID- 29001116 TI - College and Hospital Appointments. PMID- 29001118 TI - Appointments, &c. PMID- 29001120 TI - London Letter. PMID- 29001119 TI - A Discussion on Cholera; Its Epidemic Progression and Causation. PMID- 29001122 TI - Appointments, Leave, Retirement. PMID- 29001121 TI - The True Nature of the Plasmodium and of Some Other Parasitic Appearances in Blood. PMID- 29001123 TI - Vital Statistics and Sanitation. PMID- 29001124 TI - Transactions of Medical Societies. PMID- 29001126 TI - Medical News. PMID- 29001125 TI - Four Cases from the Local Fund Hospital, Chingleput. PMID- 29001128 TI - Current Medical Literature. PMID- 29001127 TI - Surgery - Antiseptic Vagaries. PMID- 29001129 TI - Report of the Leprosy Commission: Contagion. PMID- 29001130 TI - On the Study of Indigenous Drugs. PMID- 29001131 TI - A Note on Radical Cure of Hydrocele. PMID- 29001132 TI - Malaria. PMID- 29001133 TI - Progress of Sanitation in Assam. PMID- 29001134 TI - Six Cases of Cardiac Thrombosis Causing Sudden Death. PMID- 29001136 TI - Mecca and Indian Pilgrims. PMID- 29001135 TI - A Case of Carbolic Acid Poisoning. PMID- 29001137 TI - A Case of Ovariotomy. PMID- 29001138 TI - Transactions of Medical Societies. PMID- 29001139 TI - Indian Pilgrims to Mecca. PMID- 29001140 TI - Current Medical Literature. PMID- 29001141 TI - A Case of Snake-Bite: Strychnia Treatment, Recovery. PMID- 29001142 TI - Medical News. PMID- 29001143 TI - Vital Statistics and Sanitation. PMID- 29001144 TI - Appointments, Leave, &c. PMID- 29001145 TI - The Evolution of Antiseptic Surgery: A Retrospect. PMID- 29001146 TI - London Letter. PMID- 29001147 TI - Report of the Leprosy Commission: Heredity. PMID- 29001149 TI - Medico Legal Work in the District of Backergunge in 1892. PMID- 29001148 TI - Treatment of Chronic Dysentery. PMID- 29001150 TI - A Case Fracture-Dislocation of the Cervical Spinal Column. PMID- 29001151 TI - Lathyrism. PMID- 29001152 TI - Medical News. PMID- 29001153 TI - Waterborne Cholera: An Address Delivered before the Forty-Fourth Annual Meeting of the American Medical Associations, Held at Milwaukee, Wis., June 7, 1893. PMID- 29001154 TI - Appointments, Leave, &c. PMID- 29001155 TI - A Resume of Some of the More Important Facts Relating to Indian Cholera. PMID- 29001157 TI - Dysentery in Hot Countries and Its Relation to Abscess of the Liver. PMID- 29001156 TI - Notes on the Treatment and Management of Lunatics in Jails. PMID- 29001158 TI - London Letter. PMID- 29001159 TI - Ipecacuanha Sine Emetfna. PMID- 29001160 TI - Current Medical Literature. PMID- 29001162 TI - A Pasteur Institute for India. PMID- 29001161 TI - A Case of Hydrocele Reaching High into the Abdomen. PMID- 29001163 TI - Chronic Purulent Otorrhoea. PMID- 29001164 TI - Ipecacuanha and Emetine. PMID- 29001166 TI - An Argument in Favour of Tobacco. PMID- 29001165 TI - Male Sick Nurses. PMID- 29001167 TI - Epidemic Dropsy. PMID- 29001168 TI - Medical Congresses. PMID- 29001169 TI - Hepatic Abscess. PMID- 29001170 TI - A Freak of Nature. PMID- 29001171 TI - Fearful Mortality among Pilgrims. PMID- 29001172 TI - A Case of Snake-Bite. PMID- 29001173 TI - Cholera in Persia. PMID- 29001174 TI - The Proper Adoption and Use of Compound Titles. PMID- 29001175 TI - The Prevalence of Dochmus Duodenalis. PMID- 29001177 TI - A Case of Strangulated Hernia with Complications. PMID- 29001176 TI - The Bhau Daji Treatment of Leprosy. PMID- 29001179 TI - Vital Statistics. PMID- 29001178 TI - Lanoline Vaccination. PMID- 29001180 TI - Hydrophobia. PMID- 29001181 TI - Medical News. PMID- 29001183 TI - Case of Suffocation by a Fish. PMID- 29001182 TI - To Subscribers & Readers. PMID- 29001184 TI - Abstracts and Extracts. PMID- 29001185 TI - Current Medical Topics. PMID- 29001186 TI - Notes of Three Cases of Diphtheritic and Inflammatory Croup and Ulcerative Sore Throat, with Remarks on Treatment. PMID- 29001187 TI - A Case of Compound Fracture of the Skull and Spine, with Loss of Brain Substance. PMID- 29001188 TI - Cocaine in the Treatment of Hypopion. PMID- 29001189 TI - Service Notes. PMID- 29001190 TI - Withania Coagulans and Somnifera. PMID- 29001191 TI - Compound Fracture of the Skull, with Great Loss of Cerebral Matter; Recovery. PMID- 29001192 TI - Ovarian Cystic Tumour Successfully Removed by Ovariotomy. PMID- 29001194 TI - The Spray. PMID- 29001193 TI - Notes on the Treatment of Malarial Fevers with Tincture of Iodine. PMID- 29001196 TI - Abstracts and Extracts. PMID- 29001195 TI - Case of Foreign Body in the Rectum. PMID- 29001197 TI - Vital Statistics. PMID- 29001198 TI - Case of Strangulated Hernia Treated Successfully by Taxis. PMID- 29001200 TI - Gangrene of Forearm Caused by Undue Tightening of Splints Applied to a Simple Fracture of Humerus. PMID- 29001199 TI - Two Cases of Fracture of Skull with Recovery. PMID- 29001201 TI - The Supply of Medicines in Civil Dispensaries. PMID- 29001203 TI - The Action of Castor Oil. PMID- 29001202 TI - Thirty Cases of Pneumonia Amongst the XVth Sikhs at Delhi. PMID- 29001204 TI - Diabetes in India. PMID- 29001205 TI - Removal of Tattoo Marks. PMID- 29001207 TI - The Magnifying Power of Microscopes. PMID- 29001206 TI - Current Medical Topics. PMID- 29001209 TI - Another Cholera Microbe. PMID- 29001208 TI - Surgical Operations at the Mayo Hospital, Lahore. PMID- 29001210 TI - Vital Statistics-Mortality of Calcutta, Bombay and Madras. PMID- 29001212 TI - Medical Degrees: Special Letter from a Correspondent on Furlough. PMID- 29001211 TI - Two Cases of Atrophy of Liver. PMID- 29001213 TI - Necessity for Examining Vomited Matters in Cases of Suspected Poisoning. PMID- 29001214 TI - Service Notes. PMID- 29001216 TI - Vaccination for Cholera. PMID- 29001215 TI - On the Prevelance of Epidemic Roseola in Calcutta. PMID- 29001217 TI - Treatment of Cholera. PMID- 29001218 TI - Reduction of Strangulated Inguinal Hernia En Bloc-Operative Formation of Artificial Anus-Recovery. PMID- 29001219 TI - Appointments, Leave, &c. PMID- 29001220 TI - Abstracts and Extracts. PMID- 29001221 TI - The Symptoms in Datura Poisoning, with Notes of Thirty-Two Cases. PMID- 29001222 TI - Current Medical Topics. PMID- 29001223 TI - A Case of Supplementary or Second Spleen. PMID- 29001224 TI - The Ideal Physician. PMID- 29001225 TI - Medical Societies. PMID- 29001227 TI - Medical News. PMID- 29001226 TI - Unemployed Pay of Surgeons-Major. PMID- 29001228 TI - Warburg's Tincture. PMID- 29001229 TI - Service Notes. PMID- 29001230 TI - Appointments, Leave, &c. PMID- 29001231 TI - Case of Multiple Wounds Healing by Primary Union without the Employment of Antiseptics. PMID- 29001233 TI - Abstracts and Extracts. PMID- 29001232 TI - The Gokuldas Tejpal Hospital and the Local Medical Graduates. PMID- 29001234 TI - The Utilization of Condemned Criminals for Cholera Experiments. PMID- 29001235 TI - Case of Inversion of Uterus Following Delivery: Recovery, after Reduction. PMID- 29001236 TI - Electricity for Scorpion Stings. PMID- 29001237 TI - The Cause of Cholera. PMID- 29001238 TI - Current Medical Topics. PMID- 29001239 TI - Vital and Sanitary Statistics. PMID- 29001240 TI - Hurdwar Pilgrims and Cholera, More Especially with Regard to the Epidemic in 1885. PMID- 29001241 TI - Medical Societies. PMID- 29001243 TI - Medical News. PMID- 29001242 TI - Note on the Chemical Composition of the Leaves of Erythroxylon Monogynum (Vel Indicum). PMID- 29001245 TI - The Influence of Sea-Voyaging on the Genito-Urinary Functions. PMID- 29001244 TI - Litholapaxy in Male Children and Male Adults, with Notes of Three Cases of Lithotomy at the Indore Charitable Hospital. PMID- 29001247 TI - Current Medical Topics. PMID- 29001246 TI - Removal of 26 Calculi from a Prolapsed Bladder-Prolapsus of Bladder and Vagina of 25 Years' Duration Reduced Successfully. PMID- 29001248 TI - The Natural Production of Malaria and the Means of Making Malarial Countries Healthier. PMID- 29001249 TI - Medical News. PMID- 29001250 TI - A Statistical Review of 108 Cases of Glaucoma. PMID- 29001251 TI - Reduction of Dislocated Hip-Joint. PMID- 29001252 TI - Service Notes. PMID- 29001253 TI - The Utilization of Condemned Criminals for Cholera Experiments. PMID- 29001255 TI - Abstracts and Extracts. PMID- 29001254 TI - One Hundred and Twenty-Two Round Worms Discharged by a Child in Five Days. PMID- 29001257 TI - The Cause of Hepatic Abscess. PMID- 29001256 TI - The Treatment of Gonorhoea. PMID- 29001259 TI - The Poisons Used to Destroy Human Life in Bengal. PMID- 29001258 TI - Appointments, Leave, &c. PMID- 29001260 TI - The Constitutional Requirements for Tropical Life: With Special Reference to Temperaments. PMID- 29001262 TI - Current Medical Topics. PMID- 29001261 TI - Obesity in a Child. PMID- 29001263 TI - A Case of Camphor-Poisoning. PMID- 29001264 TI - Medical Societies. PMID- 29001266 TI - The Pishin Expeditionary Force. PMID- 29001265 TI - The AEtiology of Cholera. PMID- 29001268 TI - Potential Capacity of the Bladder in an Infant. PMID- 29001267 TI - Cerebral Haemorrhage, with Right Hemiplegia and Typical Aphasia. PMID- 29001270 TI - Service Notes. PMID- 29001269 TI - Two Cases of Strangulated Inguinal Hernia Operated on Successfully for Radical Cure. PMID- 29001271 TI - Leper Hospitals. PMID- 29001272 TI - Medical News. PMID- 29001273 TI - Abstracts & Extracts. PMID- 29001274 TI - Loosening of the Teeth. PMID- 29001275 TI - Case of Persistent Hiccough Treated Successfully by Ergot. PMID- 29001277 TI - Vital Statistics. PMID- 29001276 TI - The Comma-Bacillus of Koch Not a Distinct Species. PMID- 29001279 TI - Cocaine and Cataract at Lahore. PMID- 29001278 TI - Epidemic Progression of Cholera. PMID- 29001280 TI - Poisoning by Jatropha Multifida. PMID- 29001281 TI - Cure for Stammering. PMID- 29001283 TI - A Saline Intra-Venous Injection for Cholera. PMID- 29001282 TI - Vital Statistics. PMID- 29001284 TI - Glycerine. PMID- 29001286 TI - Abolition of Unemployed Pay. PMID- 29001285 TI - Pilocarpine in Ascites. PMID- 29001287 TI - The Mortality of the Globe. PMID- 29001288 TI - The True Role of the Comma-Bacillus Unveiled. PMID- 29001289 TI - Case of External Anthrax or Malignant Pustule. PMID- 29001290 TI - Haematuria Due to the Presence of a Leech in the Urethra. PMID- 29001291 TI - Enteric Fever among Soldiers in India. PMID- 29001293 TI - The Crow and the Country Doctor. PMID- 29001292 TI - Note on the AEtiology of Malarial Fever. PMID- 29001294 TI - Modes of Inducing Criminal Abortion in the Punjab. PMID- 29001296 TI - 1884. PMID- 29001295 TI - Nasal Polypi Removed by Tannic Acid Snuff. PMID- 29001297 TI - Abstracts and Extracts. PMID- 29001298 TI - Letter No. 1 from a Correspondent on How to Spend One's Furlough. PMID- 29001299 TI - Compound Fracture of Both Forearms. PMID- 29001300 TI - Current Medical Topics. PMID- 29001301 TI - Case of Traumatic Tetanus: Recovery. PMID- 29001302 TI - The Report of the English Cholera Commission. PMID- 29001303 TI - Medical News. PMID- 29001304 TI - Current Medical Topics. PMID- 29001305 TI - The Native Methods of Treating Lying-In-Women in India. PMID- 29001306 TI - The Cholera Epidemic in Thalchotiali District, Beluchistan. PMID- 29001307 TI - Traumatic Rupture of Spleen in a Case of Dengue. PMID- 29001309 TI - Indian Medical Jurisprudence. PMID- 29001308 TI - Appointments, Leave, &c. PMID- 29001310 TI - Vital Statistics and Sanitary Notes. PMID- 29001311 TI - Medical Women for India. PMID- 29001313 TI - Notes of a Research upon the Nature of Cobra-Poison. PMID- 29001312 TI - Service Notes. PMID- 29001314 TI - Medical Societies. PMID- 29001315 TI - "Enteric" Fever among Natives. PMID- 29001316 TI - Isapghol and Other Mucilaginous Seeds in the Treatment of Dysentery. PMID- 29001317 TI - Large Abscess on Back, Communicating with the Lung-Recovery. PMID- 29001318 TI - Horse Allowance to Officers Warned for Service. PMID- 29001319 TI - Repair of Columna of Nose-Lymphocele-Tenotomy-Urethral Haemorrhage-Excision of Superior Maxilla-Round-Celled Sarcomata-Amputation of Thigh for Sarcoma-Strumous Inflammation of Cervical Vertebrae. PMID- 29001320 TI - Indian Hemp as a Cause of Insanity. PMID- 29001321 TI - Current Medical Topics. PMID- 29001322 TI - Epidemic Prevalence of Cholera in Calcutta. PMID- 29001324 TI - Vital Statistics. PMID- 29001323 TI - Imperforate Anus: Operation: Recovery. Cataract with Atresia Pupilaris and Posterior Synechia. PMID- 29001325 TI - Treatment of Writer's Cramp. PMID- 29001326 TI - Service Notes. PMID- 29001327 TI - Abstracts & Extracts. PMID- 29001329 TI - Medical News. PMID- 29001328 TI - The Constitutional Requirements for Tropical Life: With Special Reference to Temperaments. PMID- 29001331 TI - The Execretion of Urea in Natives. PMID- 29001330 TI - Mess Subscriptions. PMID- 29001332 TI - A Further Series of 42 Cases of Litholapaxy. PMID- 29001333 TI - A Case of Enteric Fever in a Native. PMID- 29001334 TI - Thirty-Four Cases of Litholapaxy, with One Death. PMID- 29001335 TI - Insanity in Bengal. PMID- 29001337 TI - Assistant Surgeons' Promotion Examination. PMID- 29001336 TI - Myxoedema & Goitre in India. PMID- 29001338 TI - Excessive Discharge of Round Worms. PMID- 29001339 TI - Dermoid Cyst in Connection with Upper Eyelid and Frontal Bone: Removal. PMID- 29001341 TI - Appointments, Leave, &c. PMID- 29001340 TI - A Case of Pachydermatocele or Dermatolysis, Associated with Fibroma Molluscum. Illustrated. PMID- 29001342 TI - Bicarbonate of Sodium in Iodoform Poisoning. PMID- 29001344 TI - The Maclean Fund. PMID- 29001343 TI - Two Cases of Gastrorhexis, or Spontaneous Rupture of the Stomach. PMID- 29001346 TI - Two Cases of Dislocation on to the Dorsum Ilii Reduced by Manipulation. PMID- 29001345 TI - The Boy and the Bone-Setter. PMID- 29001347 TI - Vital Statistics. PMID- 29001348 TI - Abstracts and Extracts. PMID- 29001349 TI - Medical News. PMID- 29001350 TI - Current Medical Topics. PMID- 29001351 TI - Note on the Use of Babarang (Embelia Ribes) as an Efficient Remedy for Tapeworm. PMID- 29001353 TI - Liniment for Earache. PMID- 29001352 TI - Service Notes. PMID- 29001354 TI - Nine Cases of Ovariotomy. PMID- 29001355 TI - The Civil Department of the Indian Medical Service as a Field for Operative Surgery. PMID- 29001356 TI - Remarks on the Nature of Nerve Motion or Force. PMID- 29001357 TI - Incised Wound of Head with Fracture of Skull-Hemiplegia-Recovery. PMID- 29001358 TI - Diabetes in India. PMID- 29001360 TI - Bombay University. PMID- 29001359 TI - Researches on Snake-Venom. PMID- 29001364 TI - Letter No. 2 from a Correspondent on Furlough. PMID- 29001362 TI - Cholera in Relation to Water and Soil. PMID- 29001363 TI - Abstracts & Extracts. PMID- 29001361 TI - Medical Education in Lower Bengal. PMID- 29001365 TI - A Fatal Case of Remittent Fever in a Soldier, with Autopsy. PMID- 29001366 TI - The Topical Application of Muriate of Cocaine in a Case of Hydrophobia. PMID- 29001368 TI - Litholapaxy in India. PMID- 29001367 TI - Diseases of Children. PMID- 29001369 TI - Amchur or Dried Mango-Pulp as an Antiscorbutic. PMID- 29001371 TI - Chemical Terminology of Tea. PMID- 29001370 TI - Cocaine in Ophthalmic Surgery. PMID- 29001372 TI - Village Registration of Statistics. PMID- 29001373 TI - Surgery. PMID- 29001375 TI - Oriental Witchcraft. PMID- 29001374 TI - Foreign Body in Lower Part of Pharynx, with Formation of Abscess and Perforation of Larynx; Tracheotomy; Death; P.M. PMID- 29001376 TI - A Dentists Order. PMID- 29001377 TI - Medical Societies. PMID- 29001378 TI - Census of Medical Men. PMID- 29001379 TI - Current Medical Topics. PMID- 29001380 TI - Deformity of the Hands Caused by Absorption of the Phalangeal Bones. PMID- 29001382 TI - Strychnia Poisoning in India. PMID- 29001383 TI - Therapeutics. PMID- 29001381 TI - Five Cases of Charcoal Vapour Poisoning. PMID- 29001384 TI - Two Cases of Excision of Elbow Joint. PMID- 29001385 TI - Vital Statistics. PMID- 29001386 TI - Fever in Bengal. PMID- 29001387 TI - Litholapaxy in Male Children and Male Adults: A Second Series of Cases. PMID- 29001388 TI - A Case of Chylous Urine. PMID- 29001389 TI - Service Notes. PMID- 29001390 TI - Removal of Nitrate of Silver Stains from Hands. PMID- 29001392 TI - Annual Report of the Sanitary Commissioner with the Government of India. PMID- 29001391 TI - Field Service Kit. PMID- 29001393 TI - Vital Statistics. PMID- 29001394 TI - Where Is Urea Formed? PMID- 29001396 TI - The Struggle for Existence in Indian Forests. PMID- 29001395 TI - External Application of Ether in Vomiting. PMID- 29001397 TI - Enormous Elephantoid Growth of Leg: Amputation of Lower Extremity (Illustrated). PMID- 29001398 TI - Current Medical Topics. PMID- 29001399 TI - An Address on Cholera Enquiry. PMID- 29001401 TI - Oil of Peppermint in Burns. PMID- 29001400 TI - Nux-Vomica Poisoning of an Habituee. PMID- 29001402 TI - A Piece of Stick Introduced by a Woman into the Interior of Her Uterus for the Cure of Amenorrhoea: Removal. PMID- 29001403 TI - Is Herpes Zoster Contagious? PMID- 29001404 TI - The Sanitation of Calcutta Suburbs. PMID- 29001405 TI - A Testimonial to Dr. Docker. PMID- 29001406 TI - Three Cases of Radical Cure of Hernia. PMID- 29001407 TI - Medical News. PMID- 29001408 TI - Diagnosis of Leprosy. PMID- 29001410 TI - The Origin of Indian Hospitals. PMID- 29001411 TI - Elastic Cord for Arresting Haemorrhage in the Field. PMID- 29001409 TI - Treatment of Stammering. PMID- 29001412 TI - Management of the Third Stage of Labor. PMID- 29001413 TI - Case of Transposition of the Viscera. PMID- 29001414 TI - Obstinate Case of Obstruction of Bowel. PMID- 29001415 TI - The Ayur-Veda Sastra on Opium. PMID- 29001416 TI - Medical News. PMID- 29001417 TI - Pathology and Bacteriology: Intestinal Origin of Chlorosis, &c. PMID- 29001418 TI - Notes on the Meteorology of Cholera in Madras Presidency. PMID- 29001420 TI - Persistent Sneezing under Chloroform Anaesthesia. PMID- 29001419 TI - A Case of Cerebral Tumour. PMID- 29001421 TI - Well-Construction and the Preservation of the Purity of Well-Water. PMID- 29001423 TI - Surgical Treatment of Pulmonary Cavities. PMID- 29001422 TI - Transactions of Medical Societies. PMID- 29001425 TI - Waterborne Cholera. PMID- 29001424 TI - Permanganate of Potash as an Antidote to Opium. PMID- 29001426 TI - Medicine: Therapeutic Uses of Phenocoll-Antidote to Hydrocyanic Acid, &c. PMID- 29001427 TI - Cocaine Anaesthetic in Removal of Tumours. PMID- 29001428 TI - Vital Statistics. PMID- 29001429 TI - Hysterectomy by the Clamp Operation. PMID- 29001430 TI - Sanitation in India. PMID- 29001431 TI - Headache as a Consequence of Menorrhagia and Utero-Ovarian Irritation. PMID- 29001432 TI - Epidemic Dropsy. PMID- 29001433 TI - Appointments, Leave. PMID- 29001434 TI - Surgical Extracts: A Mode of Controlling the Circulation through the Abdominal Aorta, &c. PMID- 29001435 TI - Professor Haffkine's Method of Inoculation against Cholera. PMID- 29001436 TI - Treatment of Cases of Suppurating Ovarian Cyst, &c. PMID- 29001437 TI - Infectious Diseases and Cremation among Europeans. PMID- 29001438 TI - Miscellaneous Notes. PMID- 29001439 TI - Opium: Its Manufacture and Composition. PMID- 29001440 TI - Treatment of Chronic Hydrocephalus. PMID- 29001441 TI - History of the Opium Habit, and Opium-Poppy Culture. PMID- 29001442 TI - Surgical Extracts: Union of a Ureter-Hutchins on Leprosy-Laminectomy. PMID- 29001444 TI - Ophthalmology: Pernicious Influence of Albinism upon the Eye, &c. PMID- 29001443 TI - Pathology and Bacteriology: Jaundice from Mental Emotion, &c. PMID- 29001446 TI - Appointments, Transfers, Promotions. PMID- 29001445 TI - Obstetrics and Diseases of Women and Children. PMID- 29001448 TI - Proper Adoption and Use of Compound Titles. PMID- 29001447 TI - A Case of "Filarial Disease" of the Lymphatics in Which a Number of Adult Filaria Were Removed from the Arm. PMID- 29001449 TI - Electricity in an Obstinate Case of Eczema. PMID- 29001450 TI - The "M. D." Degree of the Calcutta University. PMID- 29001451 TI - Transactions of Medical Societies. PMID- 29001452 TI - Medicine: HystericalAphonia-Sur la Pathogenie du Rhumatisme Articulaire Aigu Frave-Beri-Beri. PMID- 29001453 TI - Vital Statistics. PMID- 29001454 TI - Opium, &c. PMID- 29001455 TI - Intolerence of Iodine. PMID- 29001456 TI - Ipecacuanha Sine Emetina. PMID- 29001458 TI - Medical News. PMID- 29001457 TI - Case of a Madrasi Woman Bitten by a Russell's Viper. PMID- 29001459 TI - Malarial Melanaemia. PMID- 29001460 TI - A Case of Cerebellar Tumour with Secondary Growths in the Meninges. PMID- 29001462 TI - The Bacteriology of Dysentery. PMID- 29001461 TI - The Thyroid Treatment of Myxoedema. PMID- 29001463 TI - An Analysis of the Symptoms Referable to the Alimentary System Observed in 250 Cases of Enteric Fever in India. PMID- 29001465 TI - Medical News. PMID- 29001464 TI - Typhoid Fever in India. PMID- 29001466 TI - Vestigia Nulla Retrorsum. PMID- 29001467 TI - Sterilised Water. PMID- 29001468 TI - Transactions of Medical Societies. PMID- 29001469 TI - Studies on the Etiology of Cholera. PMID- 29001470 TI - Erysipelas of the Face. PMID- 29001471 TI - Anchylostomiasis in Egypt. PMID- 29001473 TI - Vital Statistics and Sanitation. PMID- 29001472 TI - Some Remarks on Guinea-Worm. PMID- 29001474 TI - Note on Cholera in the Berar Province. PMID- 29001475 TI - The Treatment of Cancer of the Stomach: La Tribune Medicale, 22nd March 1894. PMID- 29001476 TI - Appointments, Leave, Acknowledgments. PMID- 29001477 TI - Enteric Fever Amongst the Troops in Paris, &c. PMID- 29001479 TI - A Case of Sarcoma of the Left Upper Extremity-Amputation at the Shoulder Joint: Recovery. PMID- 29001478 TI - Chloroform and AEther: A Comparison. PMID- 29001480 TI - Anchylostomiasis. PMID- 29001481 TI - A Case of Pulmonary Embolism. PMID- 29001483 TI - Medicine: Venesection in Diseases of the Heart. &c. PMID- 29001482 TI - The Plague in Hongkong, and the Measures to Prevent Its Introduction into Calcutta. PMID- 29001484 TI - Cases from the Emambarrah Hospital in Hughli. PMID- 29001486 TI - Rheumatic Fever with Hyperpyrexia. PMID- 29001485 TI - Eighth Inter. Congress of Hygiene and Demography. PMID- 29001487 TI - Medical News. PMID- 29001488 TI - Allahabad Magh Mela of 1894. PMID- 29001492 TI - The Proper Adoption and Use of Compound Titles. PMID- 29001491 TI - The Role of the Bacillus Coli Communis as a Pathogenic Organism. PMID- 29001493 TI - Animal Vaccine: Its Origin and Cultivation. PMID- 29001495 TI - Treatment of Diabetes. PMID- 29001494 TI - Vital Statistics and Sanitation. PMID- 29001497 TI - Ophthalmology: Subconjunctival Injections in Interstitial Keratitis, &c. PMID- 29001496 TI - Transactions of Medical Societies. PMID- 29001499 TI - Appointments, Leave, Furlough, Transfers, &c. PMID- 29001498 TI - The Case against Surgeon-Lieutenant Pearse. PMID- 29001501 TI - Diseases of Women and Children. PMID- 29001500 TI - Epidemic Dropsy. PMID- 29001502 TI - On the Relation between Atmospheric Pressure and Cholera in the Bombay Province. PMID- 29001503 TI - Diabetes. PMID- 29001504 TI - Further Observations on the Modified Operation for Extraction of Senile Cataract. PMID- 29001505 TI - Surgical Extracts: Where Pus is Formed in Quinsy? PMID- 29001506 TI - A Case of Bilateral Cerebral Haemorrhage. PMID- 29001507 TI - Waterborne Cholera: An Address Delivered before the Forty-Fourth Annual Meeting of the American Medical Association, Held at Milwaukee, Wis., June 7, 1893. PMID- 29001508 TI - Medical News. PMID- 29001509 TI - Cases from the Imambarah Hospital in Hughli. PMID- 29001511 TI - Position of Beri-Beri among Infectious Diseases. PMID- 29001510 TI - Vital Statistics and Sanitation. PMID- 29001512 TI - Transactions of Medical Societies. PMID- 29001513 TI - Appointments, &c. PMID- 29001514 TI - Epidemic Dropsy. PMID- 29001515 TI - Injury to the Cervical Cord. PMID- 29001516 TI - Medical Evidence. PMID- 29001518 TI - Surgical Extracts: Surgical Teatment of Goitre Hypertrophy of the Prostate - Rhinitis OEdematosa. PMID- 29001517 TI - Third Element of the Blood and Malaria Parasite. PMID- 29001520 TI - Miscellaneous Notes, &c. PMID- 29001519 TI - Tuberculosis of Peritoneum. PMID- 29001521 TI - The Royal Commission on Opium - General Evidence. PMID- 29001522 TI - Ophthalmology: The Therapeutic Value of Weak Lenses-Abnormal Conditions of the Eye and Uterine Diseases, &c., &c. PMID- 29001523 TI - Indian Medical Congress. PMID- 29001525 TI - Vital Statistics and Sanitation. PMID- 29001524 TI - On the Cataract Pricking of the Hindu. PMID- 29001527 TI - Appointments, Leave, Acknowledgments. PMID- 29001526 TI - Note on a Case of Obstruction of the Bowels: Presumably Due to the Presence of Common Round Worms. PMID- 29001528 TI - Enteric Fever among Natives. PMID- 29001529 TI - Snake-Bite; Treatment by Strychnine: Recovery. PMID- 29001532 TI - Eight Hundred and Fifty-Two Operations for Stone in the Bladder. PMID- 29001531 TI - Medicine: The Ingleby Lectures on the Common Forms of Dyspepsia in WomenNote on Strychnine as a Cardiac and Respiratory Stimulent. PMID- 29001530 TI - Technique of Haffkine's Anti-Choleraic Inoculations. PMID- 29001534 TI - Appointment of the Visiting Surgeon and Clinical Teacher to the Medical College. PMID- 29001533 TI - The Most Common Eye Diseases in the N.-W. P. and Oudh. Illustrated by 1,000 Cases. PMID- 29001536 TI - Medical News. PMID- 29001535 TI - Surgical Extracts: On the Treatment of Some Forms of Stone in the Bladder by Perinaeal Lithotrity the Operative Treatment of Sarcoma of the Kidney, &c., &c. PMID- 29001538 TI - Transactions of Medical Societies. PMID- 29001537 TI - A Case of Idiopathic Tetanus Treated with Sub-Cutaneous Injection of EserineSulphas: Recovery. PMID- 29001540 TI - Medical News. PMID- 29001539 TI - Vital Statistics. PMID- 29001541 TI - Intra-Peritoneal Injection in Cholera. PMID- 29001542 TI - Miscellaneous Notes. PMID- 29001543 TI - Water-Borne Cholera. PMID- 29001544 TI - Fatal Sword Wound of the Abdomen. PMID- 29001545 TI - Foecal Impaction Causing Sciatica in a Puerperal Women. PMID- 29001547 TI - Alcohol as a Therapeutic Agent. PMID- 29001546 TI - Epidemic Dropsy. PMID- 29001548 TI - A Resume of Some of the More Important Facts Relating to Indian Cholera. PMID- 29001549 TI - The Opium Question. PMID- 29001550 TI - Medicine: Traitement Chirurgical des Absces du Foie-Actions of Drugs upon the Kidney, &c. PMID- 29001552 TI - Appointments, Leave. PMID- 29001551 TI - Surgical Extracts: Saline Aperients in Peritonitis-The Bacteriological Origin of Chronic Rheumatic Joint Inflammations, &c. PMID- 29001553 TI - A Case of Acute Atrophy of the Liver. PMID- 29001555 TI - Transactions of Medical Societies. PMID- 29001554 TI - A Case of Snake-Bite Treated by Strychnine. PMID- 29001556 TI - Transposition of the Testicles. PMID- 29001557 TI - Professor Cunningham's Recent Observations on the Comma Bacillus. PMID- 29001558 TI - The Visiting Surgeon and Clinical Teacher of Surgery at the Calcutta Medical Hospital. PMID- 29001559 TI - Ophthalmology: The Operative Cure of High Myopia-Temporary Blindness, &c. PMID- 29001561 TI - Vital Statistics and Sanitation. PMID- 29001562 TI - Opthalmology: Surgical Treatment of Granular Lids -Tumours of the Optic Nerve, &c. PMID- 29001560 TI - Chloroform and AEther: A Comparison. PMID- 29001563 TI - Medical News. PMID- 29001564 TI - Observations on Typhoid OutBreaks: I.-Typhoid and "Dahi". PMID- 29001565 TI - Miscellaneous Notes. PMID- 29001566 TI - Perforation in Typhoid Treated Byexcising the Perforation, and Washing out the Peritonial Cavity, &c. PMID- 29001567 TI - A Case of Intussusception: Laparotomy: Remarks on the Mortality of Such Cases. PMID- 29001569 TI - The Pathology of Diabetes. PMID- 29001568 TI - The Operative Treatment of Acute Suppurative Peritonitis. PMID- 29001570 TI - Medical Advertisements in Lay Papers. PMID- 29001571 TI - Sanitation and Medical Relief in Rural Tracts. PMID- 29001572 TI - Medcine: Diagnostic Palpation of the Vermiform Appendix, &c. PMID- 29001573 TI - Abdominal Surgery at the Eden Hospital, Calcutta, during the Years, 92-93. PMID- 29001574 TI - Transactions of Medical Societies. PMID- 29001576 TI - A Protest. PMID- 29001575 TI - Remarks on the Operative Treatment of Stricture of the Urethra: More Particularly the Impermeable. PMID- 29001577 TI - The Future of the Wounded in War: A Note. PMID- 29001578 TI - Two Cases of Tetanus. PMID- 29001579 TI - A Case of Progressive Muscular Atrophy. PMID- 29001580 TI - Medical Fees. PMID- 29001581 TI - The Treatment of Cancer of the Stomach: La Tribune Medicale, 22nd March 1894. PMID- 29001583 TI - The Nucleins and Nuclein Therapy. PMID- 29001582 TI - Appointments-Leave-Acknowledgments. PMID- 29001584 TI - A Case of Snake-Bite: Treatment by Hypodermic Injection of Strychnia: Death. PMID- 29001586 TI - The Future of the Wounded in War. PMID- 29001585 TI - Anchylostomiasis. PMID- 29001587 TI - The Madras Govt. and Their Medical Officers. PMID- 29001588 TI - Treatment of Cholera. PMID- 29001589 TI - The Use of Quinine. PMID- 29001590 TI - Miscellaneous Notes. PMID- 29001591 TI - Medicine: Rapid Method of Demonstrating Tubercle Bacilli in Sputa-Relapses in Typhoid Fever - The Diazo-Benzoic Reaction in Urine, &c. PMID- 29001592 TI - Medical News. PMID- 29001593 TI - Haffkine's Preventive Inoculation. PMID- 29001594 TI - Abdominal Surgery at the Eden Hospital, Calcutta, during the Years, '92-93. PMID- 29001596 TI - Transactions of Medical Societies. PMID- 29001595 TI - Inoculation as a Prophylactic of Cholera. PMID- 29001597 TI - Indian Medical Congress. PMID- 29001598 TI - Rainfall and Seasonal Cholera in India. PMID- 29001599 TI - An Epidemic of Yaws in Assam. PMID- 29001600 TI - On Insanity Produced by the Abuse of Ganja and Other Preparations of Indian Hemp, with Notes of Cases. PMID- 29001601 TI - Vital Statistics and Sanitation. PMID- 29001602 TI - Cholera and Preventive Inoculation in Gya Jail. PMID- 29001603 TI - Prevention of Sore Feet. PMID- 29001604 TI - Cholera in the J. J. Hospital, Bombay. PMID- 29001605 TI - Heatstroke-Sunstroke - With Hyperpyrexia, Temperature 109 degrees . 8 F. Recovery. PMID- 29001606 TI - Antiseptic Surgery in India-In Theory and Practice. PMID- 29001608 TI - Appointments-Leave-Acknowledgments. PMID- 29001607 TI - Selections: Karlinski's Short Contributions to the AEtiology of Cholera-Measures against Cholera; the Sanitary Conditions of Lunatic Aylums, Infirmaries, &c. PMID- 29001610 TI - A Case of Liver Abscess. PMID- 29001609 TI - The Strychnia Treatment of Cobra-Bite. PMID- 29001611 TI - A Case of Sarcoma of Left Upper Jaw : Excision : Recovery. PMID- 29001612 TI - The Colombo Leper Asylum. PMID- 29001613 TI - A List of Natural Appearances in the Blood Which Have Been Mistaken for Forms of the Malaria Parasite. PMID- 29001614 TI - Medicine-Entomology Applied to Medico-Legal Medicine-Tea as a Possible Course of Plumbism-The Therapeutics of the Homologues of Quinine-Sodium Nitrate - Diagnosis of Latent Aortic Aneurism - Treatment of Tuberculosis, &c., &c. PMID- 29001616 TI - The Marriage of Syphilitics-The Treatment of Fracture by Massage-Comparative Statement of Mortality after Chloroformand Ether, &c., &c. PMID- 29001615 TI - Suggestions as to the Operation for the Radical Cure of Oblique Inguinal Hernia. PMID- 29001617 TI - Malarial Melanmia. PMID- 29001618 TI - Death under Chloroform. PMID- 29001619 TI - Good Service Pensions. PMID- 29001620 TI - On Insanity Produced by the Abuse of Ganja and Other Preparations of Indian Hemp, with Notes of Cases. PMID- 29001621 TI - Round Worms Passing through the Abdominal Wall. PMID- 29001622 TI - Medical News. PMID- 29001623 TI - Miscellaneous Notes. PMID- 29001624 TI - Case of Snake-Bite Treated with Hypodermic Injection of Strychine: Recovery. PMID- 29001625 TI - On the Abandonment of Iridectomy and the New Operation for Hard Cataract. PMID- 29001626 TI - Clinical Notes on Mycetoma Differentiating the Pale from the Black Variety. PMID- 29001627 TI - Gynaecology in Bagdad. PMID- 29001628 TI - Abdominal Surgery at the Eden Hospital, Calcutta, during the Rears '92-93. PMID- 29001629 TI - Intestinal Obstruction, by Bands-LaparotomyRecovery. PMID- 29001630 TI - Titles of Medical Officers in the Army. PMID- 29001631 TI - Transactions of Medical Societies. PMID- 29001633 TI - Vital Statistics and Sanitation. PMID- 29001632 TI - Acute Jaundice Associated with Occlusion of the Cystic Duct and a Subnormal Temperature. PMID- 29001634 TI - Appointments-Leave-Acknowledgments. PMID- 29001635 TI - Epidemic of Yaws in Assam. PMID- 29001636 TI - Testimonial to Sir Joseph Lister. PMID- 29001637 TI - Metchnikoff's Researches on the Cholera Vibrio. PMID- 29001638 TI - Contracted Liver-Death 16 Years after Removal of the Cause. PMID- 29001639 TI - Flies and Cholera Diffusion. PMID- 29001641 TI - Miscellaneous Notes. PMID- 29001640 TI - Atmospheric Pressure and Cholera in India. PMID- 29001643 TI - Vital Statistics and Sanitation. PMID- 29001642 TI - Treatmentof Guinea-Worm. PMID- 29001644 TI - Transactions of Medical Societies. PMID- 29001645 TI - Two Cases of Snake - Bite. PMID- 29001646 TI - Trephining for Hemiplegia-The Result of Injury-Recovery. PMID- 29001647 TI - A Query. PMID- 29001648 TI - The Temperature in Enteric Fever. PMID- 29001649 TI - Appointments-Leave-Acknowledgments. PMID- 29001650 TI - Varieties of the Comma Bacillus. PMID- 29001651 TI - Pathology and Bacteriology-Non-Alcoholic Cirrhosis of the Liver by Auto Intoxication of Gastro - Intestinal Origin - Floating Spleen with Twisted Pedicle Influence of Atmospheric Pressure on the Prevalence of Pneumonia - Bacteriology of Diphtheria. PMID- 29001652 TI - Surgical Extracts-Gall Bladder Surgery - Antipyrine in Painful Affections of the Bladder and Prostate - Fracture of the Patella, &c. PMID- 29001654 TI - Medicine-The Treatment of Croupous Pneumonia-Beri-Beri-Enteric Fever in India Local Treatment of Psoriosis-Salicylic Colloid in Lupus-Antitoxine Treatment of Diphtheria, &c. PMID- 29001653 TI - The Desinfection of Wells. PMID- 29001655 TI - Cholera and Bread. PMID- 29001656 TI - An Appeal. PMID- 29001657 TI - Medical News. PMID- 29001658 TI - Dysentery in Jail. PMID- 29001659 TI - Miscellaneous Notes. PMID- 29001661 TI - Presidential Address: Tropical Section, at Eight International Congress of Hygiene and Demography, Budapest: 1894. PMID- 29001660 TI - Incision of Cervix in Certain Complicated Labour Cases. PMID- 29001662 TI - Abdominal Surgery at the Eden Hospital, Calcuttta, during the Years 1892-93. PMID- 29001663 TI - Vital Statistics and Sanitation. PMID- 29001664 TI - Erratum: Yaws in Assam: Correction. AB - [This corrects the article on p. 326 in vol. 29.]. PMID- 29001666 TI - Snake Bites. PMID- 29001665 TI - Dental Caries and Cervical Abscess in Children, &c. PMID- 29001667 TI - Transactions of Medical Societies. PMID- 29001668 TI - On Insanity Produced by the Abuse of Ganja and Other Preparations of Indian Hemp, with Notes of Cases. PMID- 29001669 TI - Enteric Fever in India. PMID- 29001671 TI - Ophthalmology-Tuberculous Iritis-Blinding by Direct Sunlight, &c. PMID- 29001670 TI - Medicine-Does Previous Small-Pox in the Parents Render Their Offspring Insusceptible to the Action of Vaccine Lymph? Choloralose-Hypodermic Medication in Syphilis. PMID- 29001673 TI - A Query. PMID- 29001672 TI - Fourcases of Injury to the Thoracic Duct Occurring in the Course of Surgical Operations. PMID- 29001674 TI - The Incineration of Refuse in Calcutta and Other Towns of India. PMID- 29001675 TI - Appointments-Leave-Acknowledgments. PMID- 29001676 TI - Judicial Hanging. PMID- 29001677 TI - A Case of Snake-Poisoning Treated with Strychnia: Recovery. PMID- 29001678 TI - Obstructed Arm Presentation with Death of the Foetus-Craniotomy: Recovery. PMID- 29001679 TI - Medical News. PMID- 29001681 TI - A Case of Pyo-Pneumothorax from Perforation of a Phthisical Cavity and Pale Granular Kidney. PMID- 29001680 TI - Dr. Ranking on the Treatment of Remittent Fever, &c. &c. PMID- 29001683 TI - Vital Statistics and Sanitation. PMID- 29001682 TI - A Case of Compound Comminuted Depressed Fracture of Frontal Bone. PMID- 29001684 TI - Vital Statistics and Sanitation. PMID- 29001685 TI - Water-Borne Cholera. PMID- 29001686 TI - Further Correspondence between Sir Andrew Clark and Mr. Stanhope. PMID- 29001687 TI - Fattening on Diabetic Urine. PMID- 29001688 TI - Service Notes. PMID- 29001689 TI - Appointments, Leave, &c. PMID- 29001690 TI - Transactions of Medical Societies. PMID- 29001692 TI - A Case of Amputation at the Hip Joint. PMID- 29001691 TI - Transposed Liver and Spleen. PMID- 29001693 TI - The Pathology and Treatment of Furunculosis. PMID- 29001694 TI - Current Medical Topics. PMID- 29001695 TI - Medical News. PMID- 29001696 TI - The Absorption of Medicaments from Ointments. PMID- 29001697 TI - Cystitis and Sugar. PMID- 29001698 TI - Vital Statistics and Sanitation. PMID- 29001699 TI - On Carlsbad Treatment for Anglo-Indians. PMID- 29001701 TI - A Parasitic Protozoou in Carcinomata. PMID- 29001700 TI - Erratum: On Carlsbad Treatment for Anglo-Indians: Corrigendum. AB - [This corrects the article on p. 71 in vol. 26.]. PMID- 29001702 TI - Sir Andrew Clark and Mr. Stanhope. PMID- 29001703 TI - The Influence of Medicaments Upon the Culture of the Achorion Schonleinii and Trichophyton. PMID- 29001704 TI - Microbes and Malaria. PMID- 29001705 TI - Obstetrics, Gynaecology, and Paediatrics: Treatment of Uterine Fibroid by Vaginal Ligation of the Base of the Broad Ligament-A New Method of Treatment for Prolapse of the Uterus-Maternal Risk in Twin-Pregnancy-A New Incision in Caesarean Section. PMID- 29001707 TI - The Anti-Venomous Properties of Bile. PMID- 29001706 TI - Medicine: Beri-Beri and Rice-Medical Geography-High Altitudes for European Soldiers in Tropical Countries-Sporadic and Endemic Cretinism-Inflammations of the Colon-Test for Malingering (Feigned) Blindness-A New Form of Multiple Neuritis. PMID- 29001708 TI - London Letter. PMID- 29001709 TI - A Simple Form of Incubator. PMID- 29001710 TI - Case of Diabetes Mellitus with Very Low Specific Gravity. PMID- 29001712 TI - Education in Tropical Disease. PMID- 29001711 TI - Further Observations on the Transformation of Crescents. PMID- 29001713 TI - Medical News. PMID- 29001714 TI - Fungus-Disease of the Ear. PMID- 29001715 TI - The Source of the Error in the Popular Belief as to the Danger of Curing Itch and Other Skin Diseases. PMID- 29001716 TI - Surgery: The Radical Cure of Herniz by Zinc Chloride Injections-Silk or Catgut in Abdominal Section-Reduction of Old Dislocations of the Shoulder-An Ointment for Pruritus-Double-Pointed Tacks for Sutures-Bunion: Its Etiology, Anatomy, and Operative Treatment - Disinfectant Soap. PMID- 29001717 TI - Special Senses: Hereditary Tendency to Cataract-Eucain in Operations on the Nose, Throat and Ear. PMID- 29001718 TI - The Kala-Azar: Report and Its Critics. PMID- 29001720 TI - The Physiological Action of Human Sweat. PMID- 29001719 TI - On the Epidemic of Plague in Lower Damaun (Portuguese India), and on the Effect of Preventive Inoculation There. PMID- 29001721 TI - Some General Laws Which Govern the Evolution of Malaria. PMID- 29001723 TI - Hygiene: Addition to Quarantine Regulations to Be Observed at Ports and on the Frontiers of the United States-Notes on Practical Sanitary Science-Earthclosets and Disease-Germs-The Preservation of Sight in Infancy and Early Life-The Education of the Speaking Voice. PMID- 29001722 TI - Dysentery on Field-Service. PMID- 29001725 TI - Appointments, Transfers, Leave, &c. PMID- 29001724 TI - Heights and Weights of Prisoners. PMID- 29001726 TI - The Etiology of Kala-Azar. PMID- 29001728 TI - Laveran's Description of Texas Cattle Fever. PMID- 29001727 TI - Summary of Cases of Gunshot Wounds Received in the Mohmund and Mamund Countries and Transferred to the Base-Hospital at Nowshera for Treatment. PMID- 29001729 TI - Snake Poison Wanted. PMID- 29001730 TI - Reason and Instinct. PMID- 29001731 TI - Has Adipocere Been Observed in India? PMID- 29001732 TI - A Criticism of Dr. Rogers' Report on Kala-Azar. PMID- 29001733 TI - Kala-Azar in Madras. PMID- 29001734 TI - Eucalyptus Oil Poisoning. PMID- 29001735 TI - Necrosis of Scapula. PMID- 29001736 TI - Ages and Occupations of Plague Cases Treated at Parel Hospital, Bombay. PMID- 29001738 TI - Medicine: Malaria in the Mauritius-The Mosquito and Malaria-The Administration of Quinine, How and When-Anchylostomiasis in St. Lucia-An Effervescing Quinine Mixture-Scurvy and Uric Acid-Experimental Typhoid Fever-Alcohol and Immunity. PMID- 29001737 TI - Obstetrics, Gynaecology, and Paediatrics: Post-Mortem Delivery-Stypticin in Uterine Haemorrhage-The Ultimate Fate of Placental Tissue Retained in Utero Congenital Luxation of Knee-Extra Uterine Gestation-Antiseptic Performance of Embryotomy-Conservation of the Ovary in Hysterectomy and Hystero-Myomectomy Conservative Surgery of Uterine Appendages-Conservative Treatment of Fallopian Tube Disease. PMID- 29001739 TI - "That Comfortable Word" Malaria. PMID- 29001740 TI - Vesical Calculi: One Free, the Other Encysted. PMID- 29001741 TI - Malaria the Chief Cause of Infantile Convulsions in the Tropics. PMID- 29001742 TI - Diabetes. PMID- 29001743 TI - A Clinical Lecture on Filarial Lymphangiectasis. PMID- 29001744 TI - Appointments, Leave, &c. PMID- 29001746 TI - Plague Administration. PMID- 29001745 TI - Clamp for Circumcision. PMID- 29001747 TI - Notes on a Case of Acute Plague Septicaemia with Post-Mortem Examination. PMID- 29001748 TI - London Letter. PMID- 29001749 TI - Surgery: The Surgical Treatment of Goitre-Gelatine as a Haemostatic-Some Additional Facts Relating to Skin-Grafting-Suppuration of Meckel's Diverticulum Pulmonary Abscess; Operation: Recovery. PMID- 29001751 TI - Service Notes. PMID- 29001750 TI - The Source of the Error in the Popular Belief as to the Danger of Curing Itch and Other Skin Diseases. PMID- 29001752 TI - The New Chemical Examiners' Department. PMID- 29001753 TI - Liver Abscess: A Plea for More Accurate Diagnosis and Localisation by Exploratory Laparotomy: Cases: Round Worms Found in Abscess. PMID- 29001754 TI - Plague Prophylaxis. PMID- 29001755 TI - Calcutta Medical Society, Proceedings of the. PMID- 29001756 TI - Surgery: The Silver Treatment of Wounds-A Case of Double Floating Kidney with Recovery after Double Lumbar Nephrorraphy-Treatment of Fractures by Massage and without Fixation-Treatment of Lupus of the Face by Cauterising with Hot Air Curative Treatment of Vaginal Hydrocele by Injections of Solution of Corrosive Sublimate-Forcible Reduction of Potts' Curvature-Laparotomy in Tubercular Peritonitis. PMID- 29001757 TI - Special Senses: Painless Eye Operations-A Case of Otitis Media from Swallowing a Pin. PMID- 29001758 TI - Kala-Azar of Assam. PMID- 29001759 TI - A Case of Prostatectomy for the Radical Cure of Prostatic Stone. PMID- 29001760 TI - A Case of Idiosyncrasy of Intolerance of Quinine. PMID- 29001761 TI - Remarks upon Certain Diseases in India. PMID- 29001763 TI - Appointments, Leave, &c. PMID- 29001762 TI - A Criticism of Dr. Rogers's Report on Kala-Azar. PMID- 29001764 TI - Medical News. PMID- 29001765 TI - Cases of Hepatic Abscess of Special Interest. PMID- 29001766 TI - The Prophylaxis of Malarial Fever. PMID- 29001768 TI - Hospital Abuse. PMID- 29001767 TI - Bombay Plague in the Hooghly District. PMID- 29001769 TI - Obstetrics, Gynaecology, and Paediatrics: Antipyrine as an Anti-Galactagogue Hyperemesis Gravidarum-Quinine during Labour-Toxic Materials Absorbed from the Bowel as a Cause of Version of the Uterus-Apnoea of Premature Infants-On the Use of Senecio in Disorders of Menstruation-Phenacetin for Pain in Cancer of the Uterus-Airol in Ophthalmia Neonatorum-New Methods of Resuscitating Still-Born and Feeble-Born Infants. PMID- 29001770 TI - A Note on Dysentery in Bengal Jails. PMID- 29001771 TI - London Letter. PMID- 29001772 TI - Notes of a Case of Mycetoma of the Neck. PMID- 29001773 TI - The British Medical Association. PMID- 29001775 TI - Medicine: The Exact Treatment of Malarial Fever-The Abortive Treatment of Typhoid Yaws or Syphilis-The Value of Widal's Reaction in Typhoid-Plague Bacteriology Liver Abscess and Dysentery. PMID- 29001774 TI - Case of Mycetoma of the Abdominal Wall. PMID- 29001777 TI - The Role of the Spleen in Infective Disease. PMID- 29001776 TI - Three Cases of Abdominal Section in the Maternity Hospital, Trivandrum. PMID- 29001778 TI - Summary of Cases of Gun-Shot Wounds Received in the Mohmund and Mamund Countries and Transferred to the Base Hospital at Nowshera for Treatment. PMID- 29001779 TI - Surgery: A Note on Certain Points of Technique-A New Method for the Relief of Certain Enlargements of the Turbinated Bodies-Van Arsdale's Triangular Splint in Thirty-Three Cases of Fracture of the Shaft of the Femur in Infants and Children under Six Years-On Immediate Closure of Bladder and Abdominal Wall after Suprapubic Lithotomy. PMID- 29001780 TI - Report on a Preliminary Investigation into Malaria in the Sigur Ghat, Ootacamund. PMID- 29001781 TI - The Colonial Medical Service. PMID- 29001782 TI - Case of General Tuberculosis Simulating Malarial Cachexia. PMID- 29001784 TI - Service Notes. PMID- 29001783 TI - Segregation versus Inoculation. PMID- 29001785 TI - Obstetrics, Gynaecology and Paediatrics: The Bicycle and Gynaecology-Nephrotomy and Pregnancy-Iodoform-Ether in Cervical Catarrh-Vomiting of Pregnancy. PMID- 29001786 TI - Cholera-What Is Its Proper Therapeutic Treatment? PMID- 29001787 TI - The Chausa Camp Plague Case. PMID- 29001788 TI - Appointments, Leave, &c. PMID- 29001789 TI - Aspiration of Liver : Fatal Cases. PMID- 29001790 TI - Hygiene: Circular Letter Relating to Post-Epidemic Disinfection and AEration Issued by the Supervising Surgeon-General, U. S. Marine Hospital Service-The Sanitary Aspects of Utopia. PMID- 29001791 TI - Vital Statistics and Sanitation. PMID- 29001792 TI - Plague and Overcrowding in Bombay. PMID- 29001793 TI - London Letter. PMID- 29001794 TI - Medicine: Disease and Food-Grains-Thayer's Lectures on Malarial Fevers-The Treatment of Psilosis or Sprue-Vital Statistics in Ceylon-A New Nematode Haematozoon-Atypical Typhoid Fever-Summer Diarrhoea in Australia. PMID- 29001795 TI - A Report on Working of the Sedimentation Test in Enteric Fever. PMID- 29001796 TI - The Prospects of Indian Graduates of Medicine. PMID- 29001797 TI - The Last Case Injected by Yersin's Serum at Parel. PMID- 29001798 TI - Special Senses: Hypertrophy of the Lingual Tonsil-Ear Complications of Influenza The Ear Clinics of Berlin-Explanation of the Action of Iridectomy in Glaucoma Recovery after Recurrence of a Malignant Tumour of the Orbit-Extract of the Ciliary Body of the Ox. PMID- 29001800 TI - Suture of the Conjunctival Flap in Cataract Operations. PMID- 29001799 TI - A Clinical Lecture on the Surgical Treatment of Local Manifestations of Filarial Disease. PMID- 29001801 TI - Incubation Period of Plague. PMID- 29001802 TI - Uterus Bicornis: Removal of Half Uterus and Ovary: Recovery. PMID- 29001803 TI - Naso - Pharyngeal Polypus Operation. PMID- 29001804 TI - Rachitic Dwarf Delivered by Caesarian Section: Recovery. PMID- 29001805 TI - The Epidemic Malarial Fever of Assam, or Kala-Azar: A Reply to Criticisms. PMID- 29001806 TI - Is Malaria Infectious? PMID- 29001807 TI - London Letter: Acclimatisation of Europeans in the Tropics-Dr. Manson and Filaria Prophylaxis-The Royal Army Medical Corps with Reference to the Indian Service-The Late Dr. Partridge. PMID- 29001808 TI - Field Hospitals in the Tirah Campaign: Their Defects and Remedies. PMID- 29001809 TI - A Recent Series of 100 Operations for Stone in the Bladder, with Practical Remarks Thereon. PMID- 29001810 TI - Plague Convalescence Period. Analysis of 108 Cases. PMID- 29001811 TI - Appointments, Leave, &c. PMID- 29001813 TI - News and Service Notes. PMID- 29001812 TI - A Medical Reference Library for India. PMID- 29001814 TI - Transactions of Medical Societies. PMID- 29001815 TI - A Thousand Litholapaxies, Including 110 Perineal Litholapaxies. PMID- 29001816 TI - A Fatal Case of Plague Contracted at a Post-Mortem Examination. PMID- 29001818 TI - The Need for a Medical Library in India. PMID- 29001817 TI - Abscess of the Liver. PMID- 29001820 TI - Medical News. PMID- 29001819 TI - Some Remarks on Glare Retinalgia. PMID- 29001822 TI - Two Cases of Cerebral Compression: Trephining. PMID- 29001821 TI - The Selection of Sex. PMID- 29001823 TI - Portable Rations. PMID- 29001825 TI - A Note on Liver Abscess, Dysentery and the Amoeba. PMID- 29001824 TI - Obstetrics, Gynaecology and Paediatrics: Age Changes in the Placenta-Spurious Abortion-Ovarian Cyst in a Child 4 Months Old-Some Practical Points in Abdominal Section-Congenital Hydrocephalus Treated by Intra-Cranial Drainage. PMID- 29001826 TI - A Case Showing the Apparent Great Value of Cholera Inoculation. PMID- 29001827 TI - Weights of Prisoners as an Indication of the Class of Labour for Which They Are Fit. PMID- 29001828 TI - Morbid Anatomy. PMID- 29001829 TI - Studies in Obstetrics: The Proper Time for Instrumental Interference. PMID- 29001830 TI - Fracture of the Patella. PMID- 29001831 TI - Surgery: Surgical Treatment of Tumours of the Liver-Prostatic Hypertrophy-The Treatment of Inoperable Sarcoma by Means of Coley's Fluid-Acquired Oblique Inguinal Hernia. PMID- 29001832 TI - Sarcoma of Left Thigh and Knee: Successful Amputation of Thigh. PMID- 29001834 TI - Amendment of the Calcutta Municipal Consolidation Act of 1888. PMID- 29001835 TI - A Case of Traumatic Empyema, with Foreign Body in the Right Lung Removed by Operation: Recovery. PMID- 29001833 TI - A Case of Obstructed Labour by Fibrous Polypus; Craniotomy; Subsequent Carbolic Acid Poisoning and Recovery; Followed by Tetanus and Death. PMID- 29001837 TI - London Letter. PMID- 29001838 TI - Report on a Preliminary Investigation into Malaria in the Sigur Ghat, Ootacamund. PMID- 29001836 TI - Service Notes. PMID- 29001839 TI - Appointments, Leave, &c. PMID- 29001840 TI - Ground Water and Malaria. PMID- 29001841 TI - Medicine: Dr. Chauvin's Treatment of Cholera-Amoebic Dysentery-Antivenine in the Treatment of Leprosy-Elephantiasis and the X-Rays-The Sleeping Sickness-The Saline Treatment of Dysentery-Euchinin in Malaria-The Beri-Beri Epidemic in Dublin. PMID- 29001842 TI - Chronic Venereal Sores. PMID- 29001843 TI - Hygiene: Regulations for the Erection of New Buildings-The Sanitation of Domestic Buildings. PMID- 29001845 TI - Three Successful Ovariotomies. PMID- 29001846 TI - Medical News. PMID- 29001844 TI - Notes on Some of the Prevalent Diseases Amongst Goorkhas. PMID- 29001847 TI - A Case of Dry Gangrene. PMID- 29001848 TI - Chloroform Anaesthesia. PMID- 29001849 TI - Special Senses: Chronic Empyema of Antrum of Highmore-Cataract Extraction - The Rontgen Rays and Eye Surgery-Digestion of Inflammatory Products in Chronic Otitis Media-Chronic Symmetrical Enlargement of the Salivary and Lachrymal Glands-The Pharyngeal Pouch of Ranke-The Open Treatment of Wounds in Eye Operations-Holocain as an Anaesthetic. PMID- 29001851 TI - The Alt-Scherbitz Asylum. PMID- 29001852 TI - Registration of Deaths. PMID- 29001850 TI - The Conjunctival Flap in Cataract Extraction. PMID- 29001853 TI - Revision of Army Form a. 7. PMID- 29001854 TI - Rogers on a Circulating Medical Library in India. PMID- 29001856 TI - An Analysis of 200 Cases of Cataract Extraction. PMID- 29001855 TI - Grant on Collective Investigation in Cholera. PMID- 29001858 TI - Appointments, Leave, &c. PMID- 29001859 TI - Extraction of Cataract in India. PMID- 29001860 TI - Elliot and Maynard on Conjunctival Flap in Cataract Extraction. PMID- 29001857 TI - Large Encysted Vesical Calculus, Litholapaxy, Suprapubic Cystotomy. PMID- 29001862 TI - The Practical Training of Hospital Assistants. PMID- 29001861 TI - Operating for Cataract. PMID- 29001863 TI - Method and Results in Cataract Extraction. PMID- 29001865 TI - A Plague Congress. PMID- 29001864 TI - Intralaryngeal Papillomata, Thyrotomy: Recovery. PMID- 29001867 TI - London Letter. PMID- 29001866 TI - Extraction of a Vesical Calculus in a Female. PMID- 29001868 TI - The Epidemic Malarial Fever of Assam: A Reply to Criticisms. PMID- 29001869 TI - A Case of Supposed Cerebral Tumour, Trephining. PMID- 29001870 TI - The Danger of Aspirating the Liver. PMID- 29001871 TI - Current Topics. PMID- 29001872 TI - Further Observations on Framboesia or Yaws. PMID- 29001873 TI - Appointments, Leave, &c. PMID- 29001874 TI - Hepatic Abscess. PMID- 29001875 TI - Hereditary Tendency to Cataract. PMID- 29001877 TI - Plague Relapses. PMID- 29001876 TI - Insolation as a Zymotic Disease. PMID- 29001878 TI - Medical Education in India. PMID- 29001879 TI - The Care of the Wounded at Sea. PMID- 29001880 TI - Service Notes. PMID- 29001881 TI - Further Cases of Bubonic Plague Contracted at Plague Necropsies. PMID- 29001883 TI - Transactions of Medical Societies. PMID- 29001882 TI - The Modern Treatment of Fractures. PMID- 29001885 TI - The Abuse of the Term Malaria. PMID- 29001884 TI - Leaves from My Plague Note-Book. PMID- 29001886 TI - A New Operation for Radical Cure of Hydrocele. PMID- 29001887 TI - Sir Ranald Martin: His Life and Work. PMID- 29001888 TI - Case of Fatty Malarial Liver. PMID- 29001889 TI - Heights and Weights of Prisoners. PMID- 29001890 TI - Haemoglobinuric Malarial Fever. PMID- 29001891 TI - London Letter: Manson's Book on Tropical Diseases-Goodeve's Method of Washing Dysenteric Stools-The Mosquito Theory of Malarial Infection-Malarial Scurvy Service Dinners-The New Warrant. PMID- 29001892 TI - Three Cases of Appendicitis in Natives of India. PMID- 29001893 TI - Incubation Period of Plague. PMID- 29001894 TI - The Treatment of Hepatic Abscess. PMID- 29001895 TI - London Letter: The Edinburgh Meeting - The Journal of Tropical Medicine-Quinine and Haemoglobinuria-Obituary. PMID- 29001896 TI - Plague Epidemics in Russia : Some Historical Notes. PMID- 29001897 TI - The Post-Mortem Appearances of a Plague Case Showing Unusually Marked Extravasations of Blood. PMID- 29001899 TI - Supply of Milk. PMID- 29001898 TI - A Note on the New British Pharmacopoeia, 1898. PMID- 29001900 TI - Vital Statistics and Sanitation. PMID- 29001901 TI - On Some of the Less Common Manifestations of Filariasis: Filaria Bancrofti. PMID- 29001902 TI - Professor Koch and Malaria. PMID- 29001904 TI - Widal's Test. PMID- 29001903 TI - Malaria v. Scurvy. PMID- 29001905 TI - Appointments, Leave, &c. PMID- 29001907 TI - Some Possible Sources of Infection in Enteric Fever. PMID- 29001906 TI - The Serum Treatment of Leprosy. PMID- 29001908 TI - Case of Hysteria in a Female. PMID- 29001909 TI - Lumbar Varix. PMID- 29001910 TI - Current Topics. PMID- 29001911 TI - Contributions from Military Medical Officers. PMID- 29001913 TI - Sanitation in Bombay and Its Neighbourhood. PMID- 29001912 TI - Uniform and the New Titles. PMID- 29001914 TI - Cases of Plague Following Accidental Inoculation. PMID- 29001915 TI - Transactions of Medical Societies. PMID- 29001916 TI - Answer to Correspondent. PMID- 29001917 TI - On Some of the Less Common Manifestations of Filariasis: Filaria Bancrofti. PMID- 29001918 TI - The Presence of Bubonic Plague in Calcutta. PMID- 29001919 TI - Cases of Plague at the Chausa Plague Observation Camp. PMID- 29001921 TI - Quarters for Students. PMID- 29001920 TI - A Case of Haemato-Colpos. PMID- 29001923 TI - Service Notes. PMID- 29001922 TI - A Case of Blood Cyst of the Sciatic Nerve. PMID- 29001924 TI - Leaves from My Plague Note-Book. PMID- 29001925 TI - Plague Epidemics in Russia: Some Historical Notes. PMID- 29001926 TI - Points in the Treatment of the Complications of Enteric Fever. PMID- 29001927 TI - Erratum: A Correction. AB - [This corrects the article on p. 283 in vol. 33.]. PMID- 29001928 TI - Dhobies' Itch. PMID- 29001929 TI - London Letter: School of Tropical Medicine-The Treatment of Syphilis in the Army The New Warrant for the A.M.S. PMID- 29001930 TI - On Behalf of European and Indian Lepers. PMID- 29001931 TI - The Defects of Field Hospitals. PMID- 29001932 TI - Appointments, Leave, &c. PMID- 29001934 TI - The Study of Tropical Diseases. PMID- 29001933 TI - A Report on Kala Dukh. PMID- 29001935 TI - Report on the Cultivation of Proteosoma, Labbe, in Grey Mosquitos. PMID- 29001936 TI - Etiology of Sunstroke. PMID- 29001937 TI - Entrance Examination for the Medical Services. PMID- 29001938 TI - Transactions of Medical Societies. PMID- 29001939 TI - The Defects of Field Hospitals. PMID- 29001940 TI - The Role of the House-Fly in the Propagation of Disease. PMID- 29001941 TI - A Case of Cut - Throat: Through the Thyro-Hyoid Space. PMID- 29001942 TI - Cases in Hospital Practice. PMID- 29001943 TI - Some Possible Sources of Infection in Enteric Fever. PMID- 29001944 TI - London Letter: The Soudan Campaign-Koch and Virchow-The Tuberculosis Campaign. PMID- 29001945 TI - Accidental Plague Inoculations. PMID- 29001946 TI - Haemoglobinuria in a Case of Malarial Fever. PMID- 29001947 TI - Sarcoma of the Skull. PMID- 29001948 TI - Papillomata of Face, Etc. PMID- 29001950 TI - News and Service Notes. PMID- 29001949 TI - Leaves from My Plague Note-Book. PMID- 29001951 TI - The Need for the Term "Malarial Cachexia". PMID- 29001952 TI - Is Yaws Syphilis? PMID- 29001953 TI - Ulcerating Granuloma of the Pudenda. PMID- 29001954 TI - Vital Statistics and Sanitation. PMID- 29001955 TI - Medical News. PMID- 29001956 TI - Case of Multiple Wounds of a Dangerous and Severe Nature: Recovery. PMID- 29001957 TI - A Case of Traumatic Dislocation of the Penis. PMID- 29001958 TI - The Need of a Sanitary Service for India. PMID- 29001959 TI - Treatment of Snake Bite. PMID- 29001960 TI - Medicine-The Treatment of Intermittent Fever-Malarial Fever in Madagascar Overlooking of Mitral Stenosis-Bichromate of Potash in Certain Gastric Affections The Centenary of Vaccination, &c., &c. PMID- 29001961 TI - The Jail Duties of a Civil Surgeon. PMID- 29001962 TI - Appointments, Leave. PMID- 29001964 TI - Transactions of Medical Societies. PMID- 29001963 TI - Surgical Cases from the Chapra Charitable Dispensary. PMID- 29001965 TI - Surgical Extracts-Laparotomy for Intussusception in Very Young Children-Results of Operations for Cancer of the Breast, &c. PMID- 29001967 TI - Vital Statistics and Sanitation. PMID- 29001966 TI - Relationship of Crime to Insanity and Head-Measurement with Special Reference to Criminal Responsibility. PMID- 29001969 TI - Notes on the Technique of Snake Poison Experiments. PMID- 29001968 TI - Pathology and Bacteriology-On the Etiology of Epidemic Cerebro-Spinal Meningitis the Infections Myelites, &c., &c. PMID- 29001970 TI - Obstetrics and Gynaecology-A Study of the More Recent Frozen Sections in Their Bearing on the Mechanism of Labour and the Third Stage-The Lower Uterine Segment and Retraction Ring-Importance of Soft Parts in Labour-Engagement of the Head-The Cause of Internal Rotation-The Puerperium, &c., &c. PMID- 29001972 TI - Address Delivered in the Puri Zillah School. PMID- 29001971 TI - Observations on the Parasites of Malarial Fevers. PMID- 29001973 TI - Re-Organisation of the Sanitary Department in India. PMID- 29001974 TI - Appointments-Leave. PMID- 29001976 TI - A Case of Compound Comminuted Depressed Fracture of the Frontal Bone. PMID- 29001975 TI - Vital Statistics and Sanitation. PMID- 29001977 TI - A Contribution to the Etiology of Cholera. PMID- 29001979 TI - An Unusual Case of Small-Pox. PMID- 29001978 TI - Pathology & Bacteriology-The Serum Treatment of Disease-Pathology of the Blood Leucocytosis in Malarial Fever-The Blood in Diabetes. PMID- 29001980 TI - Medicine-The Therapeutic Value of Nuclein-Mercurial Salts in the Treatment of Diphtheria-Diphtheria Antitoxin-Watercress Typhoid-Papin in the Treatment of Chronic Gastric Ulcer, &c. PMID- 29001982 TI - Medical News. PMID- 29001981 TI - Water-Logging of the Villages along the Course of the Western Jumna Canal and Its Effects. PMID- 29001984 TI - The Kurseong Sanitarium. PMID- 29001983 TI - On the Prevalence of the Anchylostoma Duodenalis in Madras. PMID- 29001986 TI - Puerperal Eclampsia. PMID- 29001987 TI - Small-Pox in Calcutta. PMID- 29001985 TI - Surgical Extracts-The Treatment of Penetrating Wounds of the Ciliary Region and Lens-A New Operation for the Radical Cure of Haemorrhoids-Castration for the Relief of Hypertrophy of the Prostate-Removal of the Tonsils by Wire Snare. PMID- 29001988 TI - The Medical History of Bhagalpore Central Jail with Some Remarks on Jail Mortality. PMID- 29001989 TI - Tetany. PMID- 29001990 TI - On the Value of the Chemical and Bacteriological Examination of Water. PMID- 29001991 TI - Obstetrics and Gynaecology-The Employment of Glycerine for Inducing Labour-On the Prophylactic Treatment of Ophthalmic Neonatorum-On a Delivery-Pan in Use at the Present Time in Spain-On the Local Treatment of Puerperal Fever. PMID- 29001992 TI - Transactions of Medical Societies. PMID- 29001994 TI - Notes on the Examination of Malarial Blood. PMID- 29001995 TI - Snake-Bite. PMID- 29001993 TI - Surgical Cases from the Chapra Charitable Dispensary. PMID- 29001997 TI - Medicine-Calomel-Recovery from Tubercular Meningitis-Phenocoll in Malarial Fever Treatment of Flatulence-Diabetes Mellitus-Carasso's Treatment of Pulmonary Tuberculosis. PMID- 29001996 TI - Anchylostoma Duodenale : Is It Widespread in India, Assam and Ceylon, and Is It a Harmless or a Harmful Parasite? PMID- 29001998 TI - Obstetrics and Gynaecology-Why Does the Foetus Present by the Cephalic Extremity? The Treatment of Foetal Impaction by Cleidotomy-Accidents during Curettage. PMID- 29001999 TI - Medical News. PMID- 29002000 TI - Miscellaneous News. PMID- 29002001 TI - Notes of Some Cases of Surgical Practice at the Civil Hospital Gaya, in 1894. PMID- 29002002 TI - Surgical Extracts-Elbow-Joint Fractures Treated in the Position of Acute Flexion without Splints-A New Method of Treating a Hydrocele Sac after Incision-The Aseptic Treatment of Suppuration, &c. PMID- 29002003 TI - Medico-Legal Work of Civil Surgeons. PMID- 29002004 TI - The Treatment of Enteric Fever on the Antiseptic Principle. PMID- 29002006 TI - Vesical Calculus in India: Its Distribution and a Theory of Its Cause. PMID- 29002005 TI - Vital Statistics and Sanitation. PMID- 29002007 TI - The Prospects of the Indian Medical Service in Lower Bengal. PMID- 29002009 TI - Transactions of Medical Societies. PMID- 29002008 TI - Anchylostomiasis-Replies to Criticisms. PMID- 29002010 TI - A Case of Detachment of the Retina Treated Successfully by Hypodermic Injection of Pilocarpine. PMID- 29002011 TI - Pathology and Bacteriology-The Hongkong Bubonic Plague of 1894-Report on Psorosperms in Their Relation to the Etiology of Cancer, &c. PMID- 29002012 TI - Appointments, Leave. PMID- 29002013 TI - Anti-Choleraic Inoculations in India. PMID- 29002014 TI - Presidential Address in Pharmacology and Indigenous Drugs. PMID- 29002016 TI - Miscellaneous Notes. PMID- 29002015 TI - Presidential Address, Section of Pharmacology. PMID- 29002017 TI - Appointments-Leave. PMID- 29002018 TI - Indian Medical Congress. PMID- 29002019 TI - Presidential Address in Public Health. PMID- 29002021 TI - Vital Statistics and Sanitation. PMID- 29002020 TI - Presidential Address of the Congress. PMID- 29002022 TI - Summaries of Addresses in in Obstetrics, Surgery and Ophthalmology and Military Medicine and Surgery. PMID- 29002023 TI - Presidential Address in Medicine and Pathology. PMID- 29002024 TI - Medical News. PMID- 29002025 TI - Physical Drill. PMID- 29002026 TI - Presidential Address in Medico-Legal Medicine and Insanity. PMID- 29002028 TI - The Treatment of Enteric Fever on the Antiseptic Principle. PMID- 29002027 TI - Selected Cases from St. Stephen's Hospital for Women and Children, Delhi. PMID- 29002029 TI - Formaldehyde or Formol as the Disinfectant for India. PMID- 29002030 TI - A Case of Interstitial Hernia with Undescended Testis. PMID- 29002032 TI - A New Method of Preservation of the Perinaeum-On the Management of the Pregnant, Parturient and Lying-In Women Suffering from Cardiac Disease-The Diet of Nursing Mothers-Vaginal Injections during Labour-Abdominal vs. Vaginal Hysterectomy &c., &c. PMID- 29002031 TI - Anchylostoma Duodenale : Is It Widespread in India, Assam and Ceylon, and Is It a Harmless or a Harmful Parasite? PMID- 29002034 TI - Transactions of Medical Societies. PMID- 29002033 TI - Hypertrophy of the Adenoid Tissue in the Naso-Pharynx : An Analysis of One Hundred Cases. PMID- 29002035 TI - Medical and Sanitary Matters in India. PMID- 29002036 TI - Appointments, Leave. PMID- 29002037 TI - Heat in the Treatment for Lobar Pneumonia-Cold in the Treatment of Lobar Pneumonia-Water-Borne Typhoid-Electrical Treatment in Paralysis Agitans-Cardiac Therapeutics-Obstetrics and Gynaecology. PMID- 29002038 TI - Vital Statistics and Sanitation. PMID- 29002039 TI - Surgical Extracts. PMID- 29002040 TI - A Contribution to the History of Artificial Immunity. PMID- 29002041 TI - Medical News. PMID- 29002043 TI - Notes on Comparative Heights and Weights in Prisoners. PMID- 29002042 TI - Cases of Gunshot Wounds and Other Serious Injuries at the Barisal Hospital. PMID- 29002045 TI - Doctors in Parliament. PMID- 29002044 TI - Neuralgia of Kidney. Nephrotomy: Recovery. PMID- 29002046 TI - Immunity to Snake-Poison. PMID- 29002047 TI - Erratum: A Correction. AB - [This corrects the article on p. 249 in vol. 30.]. PMID- 29002048 TI - Pathology and Bacteriology: Diphtheria. PMID- 29002049 TI - A Faulty Method of Treating Hydrocele. PMID- 29002050 TI - The Bacteriological Test for Drinking Water. PMID- 29002052 TI - The Pilgrims' Ship Bill. PMID- 29002051 TI - Appointments, Leave. PMID- 29002054 TI - Transactions of Medical Societies. PMID- 29002053 TI - Typhus Never: Its Apparent Origin DeNovo. PMID- 29002055 TI - Medical News. PMID- 29002056 TI - The Late Dr. Coates. PMID- 29002057 TI - Small-Pox. PMID- 29002058 TI - The Natural History of Hardwar Fair Cholera Outbreaks. PMID- 29002059 TI - Non-Malignant Stricture of Rectum: Death from Acute Septicaemia. PMID- 29002061 TI - Vital Statistics and Sanitation. PMID- 29002062 TI - On Menstruation. PMID- 29002060 TI - Unhealthy Tracts in Bengal. PMID- 29002063 TI - Another Protest. PMID- 29002065 TI - Lithotomy in Assam. PMID- 29002064 TI - Surgical Extracts-Which Operation Is the Best for Most Cases of Haemorrhoids Rose's Operation for Trigeminal Neuralgia and Others, with Results and Remarks Antipyrin as a Vesical Analgesic. PMID- 29002066 TI - Pathology and Bacteriology-Micro-Pathology of Ostemalacia-Changes in the Bone, Changes in the Kidneys, Changes in the Blood. PMID- 29002067 TI - Medico-Legal Work in the Backergunge District. PMID- 29002068 TI - Medicine-The Immunisation of Animals against Snake-Poison-Bathing-Blood Examinations Regarding the Malarial Origin of Zoster-The Therapeutics of Papain Sterilisation of Milk-Lactophenine. PMID- 29002069 TI - Causation of Urinary Calculus. PMID- 29002070 TI - Food Adulteration. PMID- 29002071 TI - On Some Modifications in the Usual Method of Extraction of Senile Cataract. PMID- 29002072 TI - Relative Heights and Weights of Bengal Prisoners. PMID- 29002073 TI - On the Value of the Chemical and Bacteriological Examination of Water. PMID- 29002075 TI - Medicine-The Serum Treatment of Tetanus-Green Hair-Treatment of Croupous Pneumonia-The Schott Treatment of Chronic Heart Disease-Uricedin-The Standardisation of Eucalyptus Oil. PMID- 29002074 TI - Typhus Fever in Hoti Mardan and in Baluchistan. PMID- 29002076 TI - The Dangers of Strychnine in Snake-Bite. PMID- 29002077 TI - Results of Mons. Haffkine's Anti-CholeraicInoculations in Cachar. PMID- 29002078 TI - Appointments-Leave. PMID- 29002079 TI - Uncertainty of Tenure of Appointments among Senior Medical Officers in Civil Employ. PMID- 29002080 TI - Notes on a Case of Lymphadenoma(Hodgkins' Disease) in a Native. PMID- 29002081 TI - Anti-Choleraic Inoculations. PMID- 29002082 TI - Intussusception, Intestinal Obstruction, Abdominal Section and Reduction-Death from Exhaustion. PMID- 29002083 TI - Medical News. PMID- 29002084 TI - Transactions of Medical Societies. PMID- 29002085 TI - Obstetrics and Gynaecology-Vaginal Oophorectomy-Scrobutus in Infancy-Reproduction of the Uterine Mucous Membrane after Curetting-The Condition of the Pateller Reflex in Pregnant Women-Successful Removal of an Ovarian Cyst Weighing over 80lbs. PMID- 29002086 TI - Vital Statistics and Sanitation. PMID- 29002087 TI - Miscellaneous Notes. PMID- 29002089 TI - Large Pendulous Elephantoid Tumour of the Neck, Weighing 30lbs. Removal-Recovery. PMID- 29002088 TI - Vesical Calculus in India: Its Distribution and a Theory of Its Cause. PMID- 29002090 TI - Treatment of Enteric Fever on the Antiseptic Principle. PMID- 29002092 TI - Snake-Bites. PMID- 29002093 TI - The Discussion on Mons. Haffkine's Paper on Anticholeraic Inoculations. PMID- 29002091 TI - Note on the Symptoms of Filaria Medinensis or Guinea-Worm. PMID- 29002095 TI - Vital-Statistics and Sanitation. PMID- 29002094 TI - A Case of Central Sarcoma of the Lower End of Femur Disarticulation at the Hip: Death. PMID- 29002096 TI - Infectious Pneumonia. PMID- 29002097 TI - The Surgical Significance of Modern Small Calibre Rifles. PMID- 29002098 TI - Secondary Syphilitic Eruption in Abeyance until 15 Months after Contraction of the Primary Sore. PMID- 29002099 TI - Concerning Contagiousness of Small-Pox. PMID- 29002100 TI - Medical News. PMID- 29002101 TI - Obstetrics and Gynaecology-The Technique of Vaginal Hysterectomy-Treatment of Placenta Praevia by Means of Intra-Uterine Colpeurynter, &c., &c. PMID- 29002102 TI - The Micro-Pathology of Constitutional Malaria with Special Reference to Its Treatment by Alkaline Saline Mineral Waters. PMID- 29002104 TI - Transactions of Medical Societies. PMID- 29002103 TI - Malarial Influence in Abortion and Sterility. PMID- 29002105 TI - Scrotal Surgery in Mofussil Villages. PMID- 29002106 TI - Appointments-Leave. PMID- 29002107 TI - Pathology and Bacteriology-The Transmission of Bacilli through the Placenta Cultivation of the Tetanus Bacillus-Studies in the Pathology of Diphtheria-Anti Diphtheritic Serum. PMID- 29002108 TI - The Third Clause of the Cantonment Amendment Bill and the Indian Medical Congress. PMID- 29002109 TI - Cocaine Poisoning. PMID- 29002110 TI - The Pasteur Institute and Vivisection. PMID- 29002112 TI - Medical News. PMID- 29002111 TI - Cases of Gunshot Wounds and Other Serious Injuries at the Barisal Hospital. PMID- 29002113 TI - Pathology and Bacteriology-Discussion on Diphtheria-The Leucocytosis of Diphtheria under the Influence of Serum-Therapy-Obstetrics and Gynaecology-Rectal Examination of Pregnant Women-Deep Incision of the Parturient Cervix for Rapid Delivery-The Nephritis and Eclampsia of Pregnancy and Parturition. PMID- 29002114 TI - Medicine-Waters and Baths for Chronic Gout and Its Complications-The Salts of Uranium in Diabetes Melitus-Intravenous Mercurial Injections in Syphilis-The Liver as an Organ of Elemination of Corpuscular Elements-Anarcotine. PMID- 29002115 TI - A Few Cases of Surgical Practice. PMID- 29002117 TI - The Sanitary Commissionership of Bengal. PMID- 29002116 TI - Susceptibility to Disease. PMID- 29002118 TI - A Case of Revolver Wound. PMID- 29002119 TI - Antidote for Snake-Poison. PMID- 29002120 TI - Causation of Vesical Calculus. PMID- 29002121 TI - Sewage Farming in Madras and the Suitability of the System for India. PMID- 29002122 TI - The Treatment of Enteric Fever on the Antiseptic Principle. PMID- 29002123 TI - Transactions of Medical Societies. PMID- 29002124 TI - Vital Statistics and Sanitation. PMID- 29002126 TI - Notice to Medical Men. PMID- 29002125 TI - Anchylostoma Duodenale : Is It Widespread in India, Assam and Ceylon, and Is It a Harmless or a Harmful Parasite? PMID- 29002127 TI - Diaphragmatic Pleurisy. PMID- 29002128 TI - Appointments, Leave. PMID- 29002129 TI - The Symptoms and Treatment of Snake-Bite in India with Special Mention of Dr. A. Mueller's Subcutaneous Injection of Strychnine Based on the Consideration of 37 Cases. PMID- 29002130 TI - Tuberculous Infection through the Alimentary Canal. PMID- 29002132 TI - Appointments-Leave. PMID- 29002131 TI - Antitoxine in Diphtheria. PMID- 29002133 TI - Quinine and Malarial Fever in India. PMID- 29002134 TI - Recognition by the State of the Services of Members of the Medical Profession. PMID- 29002136 TI - Obstetrics and Gynaecology. PMID- 29002135 TI - A Case of Puerperal Eclampsia, Treated by Pilocarpine and Chloroform-Recovery. PMID- 29002138 TI - Medico-Legal Notes from the Mymensingh District. PMID- 29002137 TI - Medicine. PMID- 29002139 TI - Surgical Extracts. PMID- 29002140 TI - Translations from French Journals. PMID- 29002141 TI - Remarks on Gonorrhoeal Rheumatism and Gonorrhoeal Endo- and Peri-Carditis. PMID- 29002143 TI - Medical News. PMID- 29002142 TI - Notes of a Case of Ruptured Aneurism of the Right Popliteal Artery in a Burman. PMID- 29002144 TI - Vital Statistics and Sanitation. PMID- 29002145 TI - Typhus Fever in Hoti Mardan and in Baluchistan. PMID- 29002146 TI - Medico-Legal Work in District Backergunge. PMID- 29002148 TI - Cholera and Filters. PMID- 29002147 TI - Diphtheria and Antitoxin. PMID- 29002149 TI - Diphtheria Researches. PMID- 29002150 TI - Vital Statistics and Sanitation. PMID- 29002151 TI - A Method of Dealing with Very Large Calculi in Bladder. PMID- 29002152 TI - Selections from German Journals. PMID- 29002153 TI - Medicine-The Gouty Heart-Disinfection-Test for the Contamination of Well-Water The Infective Period of Syphilis-Treatment of Typhoid Fever-The Prevention of Phthisis, &c., &c. PMID- 29002154 TI - The Supposed Influence of Tropical Climate on Menstruation. PMID- 29002155 TI - Scrotal Surgery in Mufasal Villages. PMID- 29002156 TI - Complete Rectal Prolapse Treated by Ventro-Fixation of the Rectum. PMID- 29002157 TI - Diabetes Mellitus and Its Prevention. PMID- 29002158 TI - Comparative Heights and Weights of Prisoners in Bengal Jails. PMID- 29002159 TI - A Contribution to the Etiology of Cholera. PMID- 29002160 TI - A Case of Swollen Testicles and Intermittent Fever. PMID- 29002161 TI - Appointments-Leave. PMID- 29002163 TI - The Surgical Significance of Small Calibre Rifles-III. PMID- 29002162 TI - The Possibility of a Special Sanitary Service for the Mufasal. PMID- 29002164 TI - Diphtheria and Anti-Toxine. PMID- 29002166 TI - Enteric Fever in India. PMID- 29002165 TI - Obstetrics and Gynaecology-The Origin of Papillomatous Cysts-An Axis-Traction Forceps-A Study of Puerperal Fever or Septico-Pyaemia-Treatment of Vesico-Vaginal Fistula by Operation from within the Bladder. PMID- 29002168 TI - Surgn-Maj.-Genl. Rice, M.D., M.R.C.S., C.S.I. PMID- 29002167 TI - Medical News. PMID- 29002170 TI - Transactions of Medical Societies. PMID- 29002169 TI - The Need of an Isolation Hospital for Calcutta. PMID- 29002172 TI - Transactions of Medical Societies. PMID- 29002173 TI - A Case of Meningocele. PMID- 29002171 TI - A Remarkable Case of Quinine Poisoning. PMID- 29002174 TI - Acute Leuchaemia-A Study of Anaemia, Etc.-Pernicious Anaemia-Gonorrhoeal Rheumatism, Etc.-Thymol as an Anthelmintic-Treatment of Erysipelas-The Physiological Actions of Sparteine, &c. PMID- 29002175 TI - Observations on Cholera in India. PMID- 29002176 TI - A Contribution to the Etiology of Cholera. PMID- 29002177 TI - Obstetrics and Gynaecology: Sugar in Uterine Inertia-The Minute Anatomy of the Fallopian Tubes-The Incision in Abdominal Surgery-The Treatment of Asphyxia Neonatorum-Restoration of Life by Rhythmical Tractions on the Tongue-Care of the Navel-On Puerperal Albuminuria and Convulsions, &c. PMID- 29002178 TI - Diabetic Coma in a Child. PMID- 29002179 TI - Appointments-Leave. PMID- 29002181 TI - On the Prophylaxis of Malarial Fevers. PMID- 29002180 TI - A Suggestion. PMID- 29002182 TI - Filarial Disease. PMID- 29002183 TI - The Cantonment Bill. PMID- 29002185 TI - The Small-Pox Epidemic in Calcutta. PMID- 29002184 TI - Puerperal Eclampsia. PMID- 29002186 TI - Typhoid Fever in a Native of India. PMID- 29002188 TI - The Surgical Significance of Small Calibre Rifles.-II. PMID- 29002187 TI - Excision of the Tongue. PMID- 29002189 TI - Medical News. PMID- 29002190 TI - Vital Statistics and Sanitation. PMID- 29002191 TI - The Pasteur Filter. PMID- 29002192 TI - Scrotal Surgery in Mofussil Villages. PMID- 29002193 TI - Note on Dr. Arthur Powell's Paper on "Certain Intestinal Parasites". PMID- 29002194 TI - Ankylostoma Duodenale. PMID- 29002195 TI - Medical Ethics. PMID- 29002196 TI - The Services in 1898. PMID- 29002197 TI - The Madras Plague Case. PMID- 29002198 TI - Current Topics. PMID- 29002199 TI - Haematuria or "Blackwater" Fever in India. PMID- 29002200 TI - Odd Notes. PMID- 29002202 TI - The Radical Cure of Hernia. PMID- 29002201 TI - Plague Declaration: Plague in Calcutta. PMID- 29002203 TI - Service Notes. PMID- 29002204 TI - Plague in Monkeys and Squirrels. PMID- 29002205 TI - Medical Zoology: Further Researches upon the Cycle of Human Malaria in the Body of the Mosquito. PMID- 29002207 TI - Serum-Treatment of Leprosy. PMID- 29002206 TI - Multiple Visical Calculi in a Child. PMID- 29002209 TI - The Saline Treatment of Dysentery. PMID- 29002208 TI - Absence of Syphilis in Fiji. PMID- 29002210 TI - Surgical Cases: Treated in the Sambhu Nath Pandit Hospital, Calcutta. PMID- 29002212 TI - Mosquito-Theory of Malaria. PMID- 29002211 TI - A Case of Severe Syphilis with Prolonged Pyrexia. PMID- 29002214 TI - Congenital Cystic Tumour. PMID- 29002213 TI - A Case of Dislocation of the Trapezoid Bone,Illustrated by a Skiagraph. PMID- 29002215 TI - Gunshot Wounds in the Late Frontier War. PMID- 29002216 TI - The Queen's Visit to Netley. PMID- 29002217 TI - Plague Pills. PMID- 29002218 TI - Service Notes. PMID- 29002219 TI - Current Topics. PMID- 29002221 TI - Dysentery in English Asylums and Indian Jails. PMID- 29002220 TI - Cases of Abdominal Section. PMID- 29002223 TI - The Late Surgeon-General Maclean. PMID- 29002222 TI - Tubercular Disease of the Caecum. PMID- 29002224 TI - Instruction in Use of Roentgen Rays. PMID- 29002225 TI - The School of Tropical Medicine. PMID- 29002226 TI - Tuberculosis in India. PMID- 29002227 TI - Medical Societies. PMID- 29002229 TI - The Introductories. PMID- 29002230 TI - Keloid Growths. PMID- 29002231 TI - Hypnotic Therapeutics in India. PMID- 29002232 TI - Collection of Mosquitos and Their Larvae. PMID- 29002233 TI - A Case of Abscess of the Spleen. PMID- 29002236 TI - Heat Apoplexy. PMID- 29002235 TI - Thermic Fever. PMID- 29002234 TI - Stricture of the Pylorus, Gastrotomy. PMID- 29002238 TI - The "Practitioner" on Netley. PMID- 29002237 TI - Dipterous Larvae. PMID- 29002239 TI - The Technique of Serum Diagnosis. PMID- 29002240 TI - Current Topics. PMID- 29002241 TI - Manson's Generalizations. PMID- 29002242 TI - Cases of Cerebro-Spinal Fever. PMID- 29002243 TI - The London School of Tropical Medicine. PMID- 29002244 TI - Service Notes. PMID- 29002245 TI - Enteric Fever among Natives. PMID- 29002246 TI - The Crusade against Vermin. PMID- 29002248 TI - Enteric Fever in India. PMID- 29002247 TI - Enteric Fever in Natives. PMID- 29002249 TI - The Boom in Tropical Medicine in England. PMID- 29002251 TI - Secret Commissions. PMID- 29002250 TI - Infectiousness of Malarial Fever and Kala-Azar. PMID- 29002253 TI - Current Topics. PMID- 29002252 TI - Wanted Mosquitos. PMID- 29002254 TI - Medical Dusturi in India. PMID- 29002255 TI - Extermination of Malaria. PMID- 29002256 TI - The Prognosis of Guinea-Worm in Its Relation to the Assurance of Native Lives in India. PMID- 29002258 TI - Teeth-Blows in Their Medico-Legal Aspect. PMID- 29002259 TI - A Case of Ulceration of the Caecum Followed by Multiple Abscesses of the Liver. PMID- 29002260 TI - Rickets in India and Burma. PMID- 29002261 TI - A Word for Netley. PMID- 29002262 TI - What Is the "Hill Fever of Mysore and Deccan"? PMID- 29002264 TI - Service Notes. PMID- 29002263 TI - Increase of Vaccination in England. PMID- 29002265 TI - Medical Science and the Study of Nature: Lectures Introductory to the Course on Chemistry at the Medical College, Calcutta, Session 1899. PMID- 29002266 TI - Vaccine-Virus and Transmission of Disease. PMID- 29002267 TI - Service Notes. PMID- 29002269 TI - Cantharides as a Haemostatic in Haematuria. PMID- 29002270 TI - Current Topics. PMID- 29002272 TI - X-Rays in Military Surgery. PMID- 29002271 TI - Radical Cure of Hydrocele by Incision and Eversion. PMID- 29002273 TI - Tetanus in Calcutta. PMID- 29002274 TI - Medical Societies. PMID- 29002276 TI - Combined Typhoid and Malarial Infection. PMID- 29002275 TI - Segregation in Hindu Ritual. PMID- 29002277 TI - Two Cases of Poisoning by Oleander: (NERIUM ODORUM). PMID- 29002278 TI - Notes on Skin Diseases: Sclerotising Granuloma of the Pudenda. PMID- 29002279 TI - The Indian Section of the British Pharmacopoeia. PMID- 29002280 TI - A Case of Traumatic Diaphragmatic Hernia. PMID- 29002281 TI - A Case of Peripheral Neuritis Probably Malarial. PMID- 29002282 TI - Suppression of Consumption. PMID- 29002283 TI - Tuberculosis and Milk Supply. PMID- 29002284 TI - Oxygen and Permanganate of Potash in the Treatment of Plague. PMID- 29002285 TI - Antitoxin in Tetanus in Calcutta. PMID- 29002286 TI - Unclassified Fevers. PMID- 29002287 TI - Two Cases of Abdominal Section with Unusual Complications. PMID- 29002288 TI - A New Disease from East Africa. PMID- 29002289 TI - Dufferin Hospital in Bengal. PMID- 29002292 TI - Sickness and Mortality in Indian Jails. PMID- 29002291 TI - Current Topics. PMID- 29002290 TI - Inoculation of an Entire Community with Haffkine's Plague Vaccine. PMID- 29002293 TI - Boom in Tropical Medicine. PMID- 29002294 TI - Service Notes. PMID- 29002295 TI - Nitric Peroxide as a Disinfectant in Plague and Jigger. PMID- 29002296 TI - Cause and Prevention of Heat Apoplexy in the Army. PMID- 29002298 TI - Riding the Tropical Hobby Too Hard. PMID- 29002297 TI - The Alcoholic Liquors of India. PMID- 29002299 TI - Cerebro-Spinal Fever in Alipur Central Jail. PMID- 29002300 TI - An Outbreak of Severe Diarrhoea Traced to Food. PMID- 29002301 TI - Medical Societies. PMID- 29002302 TI - Mosquitoes and Malaria. PMID- 29002303 TI - Dysentery in English Asylums and Jails. PMID- 29002304 TI - Abdominal Surgery at Raipur. PMID- 29002305 TI - Filarial Metamorphosis in the Mosquito. PMID- 29002306 TI - Tropical Disease outside the Tropics. PMID- 29002307 TI - Sanitation in Cantonment. PMID- 29002308 TI - The Cause of Cancer. PMID- 29002309 TI - Therapeutical Notes. PMID- 29002310 TI - The Coroner in the Mofassal. PMID- 29002311 TI - Dr. Bahadurji's Motion. PMID- 29002312 TI - The Public Medical Services. PMID- 29002313 TI - A Case of Cholecystotomy. PMID- 29002316 TI - Service Notes. PMID- 29002314 TI - Entertainments. PMID- 29002317 TI - Malarial Apoplexy. PMID- 29002319 TI - Municipal Engineering in Bengal. PMID- 29002318 TI - Current Topics. PMID- 29002321 TI - The Business of the Meeting. PMID- 29002320 TI - A Disclaimer. PMID- 29002322 TI - The Tropical Section. PMID- 29002323 TI - The British Medical Association at Portsmouth. PMID- 29002324 TI - Microscopical Examination of the Blood in Cases of Fever in India. PMID- 29002325 TI - Certain Cases of Hyperpyrexia. PMID- 29002326 TI - A Case of Caesarean Section during Labour. PMID- 29002327 TI - Insanity in India. PMID- 29002328 TI - British Medical Association Meeting at Portsmouth. PMID- 29002330 TI - Excursions. PMID- 29002329 TI - Notes on the Use of Sulphate of Cinchonidine as a Prophylactic. PMID- 29002331 TI - Dipterous Larvae in the Human Alimentary Canal. PMID- 29002332 TI - Corrigenda. AB - [This corrects the article on p. 328 in vol. 34.]. PMID- 29002333 TI - A Case of Pseudo-Hypertrophic Muscular Paralysis. PMID- 29002334 TI - The Examination of the Blood in Malarial Fever. PMID- 29002335 TI - Two Cases of Peritonitis (One Caused by Tubercle and One by Enteric Fever) in Natives of India. PMID- 29002336 TI - Alleged Infectiousness of Malaria. PMID- 29002337 TI - Medical Societies. PMID- 29002338 TI - The Anti-Venene Treatment of Leprosy. PMID- 29002339 TI - A Case of Macroglossia. PMID- 29002340 TI - Service Notes. PMID- 29002341 TI - Field-Hospital Operation-Tables. PMID- 29002342 TI - A New Fashoda Incident: The Italian Flag Hoisted on the Mosquito-Theory. PMID- 29002343 TI - The Preventive Treatment of Infective Surgical Diseases. PMID- 29002344 TI - Scurvy in Indian Jails. PMID- 29002345 TI - Infection of Birds with Proteosoma by the Bites of Mosquitoes. PMID- 29002346 TI - Accidental Plague Inoculation. PMID- 29002348 TI - Asst.-Surgn. C. Ringrow. PMID- 29002347 TI - Diseased Arteries in Natives. PMID- 29002349 TI - Heights and Weights. PMID- 29002351 TI - The Plague in Vienna. PMID- 29002350 TI - Obstruction of the Bowel. PMID- 29002352 TI - Correspondence. PMID- 29002353 TI - Cancer in Kashmir. PMID- 29002354 TI - Egyptian Insanitation. PMID- 29002356 TI - Malarial Parasites in Fever Cases. PMID- 29002355 TI - A Case of Renal Calculus. PMID- 29002357 TI - Indian Plague Commission. PMID- 29002358 TI - Serum Treatment of Leprosy-Guaicol. PMID- 29002359 TI - A Simple Bed-Rest. PMID- 29002360 TI - A Year's Surgery in the Charitable Hospitals of the Punjab, Bengal and Madras. PMID- 29002361 TI - A Suggestion on the Formation of Crescentic Bodies in Malaria. PMID- 29002362 TI - Criminal Abortion in India. PMID- 29002363 TI - Public Health and Sanitation. PMID- 29002364 TI - Tropical Diseases at the U. S. Camp in Cuba. PMID- 29002365 TI - Surgical Cases: Treated in the Sambhu Nath Pandit Hospital, Calcutta. PMID- 29002366 TI - Current Topics. PMID- 29002367 TI - Herpes of Intercostal & Intercosto - Humeral Nervearea. PMID- 29002368 TI - Ulceration of Caecum Followed by Multiple Abscess of Liver. PMID- 29002370 TI - Current Topics. PMID- 29002369 TI - Keloid Nature of "Fibrous" Tumours of Auricle. PMID- 29002371 TI - Preventive Inoculation against Enteric Fever. PMID- 29002372 TI - Cerebellar Abscess: Trephining-Death. PMID- 29002373 TI - Service Notes. PMID- 29002374 TI - Medical Science and the Study of Nature: Lectures Introductory to the Course on Chemistry at the Medical College, Calcutta, Session 1899. PMID- 29002375 TI - The Extirpation of Malaria. PMID- 29002376 TI - Tuberculosis Congress at Berlin. PMID- 29002377 TI - Diseases Due to Self-Empoisoning or Auto-Intoxications. PMID- 29002378 TI - A Life Assurance Congress. PMID- 29002380 TI - Scarlatina in India. PMID- 29002381 TI - Dermatitis Exfoliativa Neonatorum: Ritter's Disease. PMID- 29002383 TI - Influenza Epidemic. PMID- 29002382 TI - Sawdust Urinals. PMID- 29002384 TI - The Treatment of Carbuncle. PMID- 29002385 TI - The Mussack and Typhoid. PMID- 29002386 TI - The Jigger or Chigo Pest. PMID- 29002388 TI - Antitoxic Use of Bile in Hindu Medicine. PMID- 29002387 TI - A Series of Cases of Compound Depressed Fracture of the Skull. PMID- 29002390 TI - Treatment of Piles and Allied Affections, Including Pruritus Ani. PMID- 29002389 TI - Is Medical Enthusiasm Decadent in Calcutta? PMID- 29002391 TI - A Case of Hypertrophy of the Toes. PMID- 29002392 TI - Medical Ethics. PMID- 29002393 TI - Two Recent Cases of Successful Operation for Impacted Stone in the Ureter. PMID- 29002394 TI - A Subject for Research. PMID- 29002395 TI - Its Victims. PMID- 29002397 TI - The British Medical Association. PMID- 29002396 TI - Therapeutical Notes. PMID- 29002399 TI - Indian Hospital Reports: Ancient and Modern. PMID- 29002398 TI - Cases in Mofassil Dispensary. PMID- 29002400 TI - How to Remain Young. PMID- 29002401 TI - Anchylostoma in the North-Western Provinces. PMID- 29002402 TI - Inspection of Dispensaries. PMID- 29002403 TI - Need for Medical Societies in India. PMID- 29002404 TI - Current Topics. PMID- 29002405 TI - Kashmir Mission Hospital: A Year's Surgical Work. PMID- 29002407 TI - Service Notes. PMID- 29002406 TI - Cases of Liver Abscess and Hydatid Treated in Berhampur Hospital during the Year 1898. PMID- 29002408 TI - Relapsing Fever (Sunjar) in the Kumaon Himalayas. PMID- 29002409 TI - The Latest Service Examinations. PMID- 29002410 TI - Pneumonia Since the Influenza Epidemic. PMID- 29002414 TI - The Prophylactic Issue of Quinine. PMID- 29002411 TI - A Case of Rupture of the Gravid Uterus: Abdominal Section and Removal of Foetus Recovery. PMID- 29002413 TI - Case of Alcoholic Peripheral Neuritis: Peripheral Neuritis of the Pneumogastric. With Comments upon the Case. PMID- 29002415 TI - Case of Acute Pulmonary OEdema during Chloroform Inhalation-Death. PMID- 29002416 TI - The Crusade against the Mosquito. PMID- 29002417 TI - The Suggested New Heading "Fevers Not Classified". PMID- 29002418 TI - Cinchonidine and Wrightia Antidysenterica as Prophylactics against Dysentery and Malaria. PMID- 29002419 TI - Note on the Prophylactic Use of Quinine and Cinchonidine. PMID- 29002420 TI - An Unpigmented Haemamoeba Found in Chronic Malarials. PMID- 29002421 TI - An Outbreak of Fever Attributed to Mosquitos. PMID- 29002423 TI - Cerebro-Spinal Fever. PMID- 29002422 TI - Dr. Haffkine at the Royal Society. PMID- 29002424 TI - Notes on Three Cases of Interest. PMID- 29002426 TI - The Plague in Egypt. PMID- 29002425 TI - The Teeth of Healthy Prisoners. PMID- 29002427 TI - Snake Poison & Plague. PMID- 29002428 TI - Abdominal Surgery at Raipur. PMID- 29002429 TI - Service Notes. PMID- 29002430 TI - Bengal Medical Institutions. PMID- 29002432 TI - Plague in Ancient India. PMID- 29002431 TI - Cerebro-Spinal Fever at Omdurman. PMID- 29002433 TI - Glycerin vs. Lanolin Lymph. PMID- 29002434 TI - The Cultivation of the Quartan Parasite in the Mosquito. PMID- 29002435 TI - The Laveran Body in Birds: Experiments Performed on Birds in the Temporary Laboratory of the Hyderabad Medical School, September 1898-September 1899. PMID- 29002436 TI - Plague on S. S. Carthage. PMID- 29002437 TI - Cases from Hospital Practice. PMID- 29002438 TI - A Case of Continued Fever Ending Fatally. PMID- 29002441 TI - Bad Teeth among Sepoys. PMID- 29002440 TI - Rational Dress for the Soldier. PMID- 29002442 TI - District Medical Histories. PMID- 29002443 TI - Chondrocarcinoma of the Testicle. PMID- 29002444 TI - Proposed Sale of Poisons Act. PMID- 29002445 TI - Unpigmented Amoebae. PMID- 29002446 TI - The Physical Requirements of the Public Services. PMID- 29002447 TI - Case of Scarlatina in India. PMID- 29002448 TI - Enteric Fever in Natives of India. PMID- 29002449 TI - Surgical Training for Military Surgeons. PMID- 29002450 TI - Medical Societies. PMID- 29002451 TI - Acute Tetanus Treated by Intracerebral Injection of Tetanus Antitoxin. PMID- 29002452 TI - Extermination of Mosquitos. PMID- 29002453 TI - Scarlatina in India. PMID- 29002454 TI - Case of Acute Pulmonary OEdema during Chloroform Inhalation-Death. PMID- 29002455 TI - Infective Cicatrising Granuloma or "Ulcerating Granuloma" of Manson. PMID- 29002456 TI - Service Notes. PMID- 29002457 TI - Notes on Certain Cases of Hyperpyrexia. PMID- 29002458 TI - Current Topics. PMID- 29002459 TI - The Administration of Antiperiodics & Iron. PMID- 29002460 TI - Serum Treatment in Typhoid Fever. PMID- 29002461 TI - Cholera Inoculation for Coolies. PMID- 29002462 TI - Extirpation of the Three Lower Coccygeal Vertebrae for Coccygodinia. PMID- 29002464 TI - Serum Treatment in Syphilis. PMID- 29002463 TI - A Short Note on the Change the Malarial Parasite Undergoes in the Mosquito. PMID- 29002465 TI - Municipal Rules for the Prevention of Cholera. PMID- 29002466 TI - Obstetrics and Gynaecology-Albuminuria in Pregnancy-Eclampsia-Asphyxia Neonatorum. PMID- 29002467 TI - Medicine-Tests for Sugar, Albumen, and Mucin-Rampoldi's Sign in Phthisis Pharmacology of Purgatives. PMID- 29002468 TI - Medical News. PMID- 29002469 TI - The Venomous Ophidians of Colombia, South America. PMID- 29002470 TI - Otitis Media - Trephining. PMID- 29002471 TI - Service Notes. PMID- 29002472 TI - A Case of Complete Closure of Anus, Rectum Normal. PMID- 29002473 TI - Cases in the Delhi Mission Hospital. PMID- 29002474 TI - Puerperal Convulsions during Delivery: Craniotomy. PMID- 29002475 TI - Transactions of Medical Societies. PMID- 29002476 TI - Directions for the Use of Mallein (Research Laboratory, Royal Veterinary College) Rules Regarding Vaccination. PMID- 29002477 TI - Vital Statistics and Sanitation. PMID- 29002478 TI - The Presidential Address at the Calcutta Medical Society. PMID- 29002479 TI - A Case of Macroglossia. PMID- 29002480 TI - Appointments, Leave, &c. PMID- 29002481 TI - Surgical Cases in the Gaya Hospital. PMID- 29002483 TI - Medical News. PMID- 29002482 TI - Myxo-Sarcoma of the Arm, Amputation at the Shoulder-Joint. PMID- 29002484 TI - Malaria. PMID- 29002485 TI - Errata in July Report. AB - [This corrects the article on p. 253 in vol. 30.]. PMID- 29002486 TI - Service Notes. PMID- 29002487 TI - The Boiling of Drinking Water. PMID- 29002488 TI - Vital Statistics and Sanitation. PMID- 29002489 TI - Obstetrics and Gynaecology-An Original Operation for the Radical Relief of Uterine Flexions & Eclampsia: Its Treatment, and a Report of 126 Cases Observed in the Leipsic Maternity Hospital-The Treatment of Puerperal Fever by Injections of Serum-Preventive Treatment of Inflamed Breasts-An Operation for the Cure of Incontinence of Urine in the Female-A Contribution to the Pathological Anatomy of Puerperal Eclampsia-Atropine in Uterine Haemorrhage. PMID- 29002491 TI - Mr. Hart on Prison Diet in Bengal: Error ubique patet; falsa est doctrina periti. PMID- 29002490 TI - Surgical Extracts-New Posture for Major Operations within the Nasal Cavities-The Treatment of Epididymitis and Orchitis-A New Operation for Nephrorrhaphy-Surgical Aspects of Tuberculosis-Antipyrine and Tannic Acid as a Styptic. PMID- 29002492 TI - A Note on the Nutritive Values of the Dietaries of Bengal Jails. PMID- 29002493 TI - An Analysis of Three Hundred Cases of Cataract Extraction. PMID- 29002494 TI - M. Haffkine's Explanation of His Inoculation Report Forms. PMID- 29002495 TI - On the Use of Calcium Chloride to Lessen Haemorrhage during Operations: With an Illustrative Case. PMID- 29002496 TI - Mr. Hankin & M. Calmette's Serum. PMID- 29002497 TI - Medicine-The Isolation and Incubation Periods of Infectious Diseases-Observations on Epidemics of Cholera in India, with Special Reference to Their Immediate Connection with Pilgrimage-Embarrassed Respiration-The Diagnostic Value of Sudden and Acute Pain as a Symptom in Abdominal Disease-Nitroglycerine for Sciatica Methods of Preparing Sputa for the Staining of Tubercle Bacilli-The Prevention of Sea-Sickness in Short Voyages. PMID- 29002498 TI - Extracts from the French Journals-Hydatid of the Ilium and Sacrum-Lupus of the Tongue. PMID- 29002499 TI - Appointments, Leave, Acknowledgments, &c. PMID- 29002500 TI - Ne Sutor Ultra Crepidam. PMID- 29002501 TI - Fibro-Cystic Tumour of the Uterus-Hysterectomy: Recovery. PMID- 29002502 TI - Obstetrics and Gynaecology-Worcester's Method of Rendering Cow's Milk (Which Is Believed to Be Poor in Lactalbumin) as Nearly as Possible an Equivalent for Mother's Milk-Uncontrollable Vomiting of Pregnancy-Bacteriology of the Birth Canal - Bromoform in Whooping Cough-Placenta Praevia: Its Rational Treatment. PMID- 29002505 TI - Treatment of Malarial Fever. PMID- 29002503 TI - Pathology and Bacteriology-The Detection of the Diphtheria Bacillus. PMID- 29002504 TI - Ophthalmology-Cataract Operations between the Ages of 80 and 90, with a Table of Cases-Prognostic Significance of Albuminuric Retinitis-Extensive Colloid Changes in the Choroid with Report of Cases-Traumatic Enophthalmos, with a Case-Which Canaliculus to Slit for Probing the Nasal Duct? PMID- 29002506 TI - Diabetes. PMID- 29002507 TI - Medical News. PMID- 29002508 TI - A Case of Milk Secretion without Pregnancy. PMID- 29002509 TI - Criminology. PMID- 29002510 TI - Two Cases of Symphysiotomy. PMID- 29002512 TI - Transactions of Medical Societies. PMID- 29002511 TI - Creasote as an Antipyretic. PMID- 29002513 TI - The Etiology of Malarial Fever, with Special Reference to the Ground-Water Level and the Parasite. PMID- 29002514 TI - Some Practical Points Respecting the Malarial Parasite. PMID- 29002515 TI - The Deciduoma Malignum. PMID- 29002516 TI - Vital Statistics and Sanitation. PMID- 29002517 TI - Antivenene as an Antidote for Snake-Bite. PMID- 29002518 TI - Appointments, Leave, Acknowledgments, &c. PMID- 29002519 TI - Treatment of Malarial Fever. PMID- 29002520 TI - A Supply of Snake Venom Antitoxin for India. PMID- 29002521 TI - Notes on Sanitation in Barracks and on the March in India. PMID- 29002523 TI - The Investigation of Malaria in India. PMID- 29002522 TI - Note on a Case of Secondary Syphilis Modified by Enteric Fever. PMID- 29002524 TI - Note on the Prevalence of Molluscum Contagiosum in the Mymensingh District. PMID- 29002525 TI - Appointments, Leave, &c. PMID- 29002526 TI - M. Haffkine on the Inoculation of Coolies. PMID- 29002527 TI - The Proposed Indian Medical Service Club. PMID- 29002528 TI - The Disinfection of Wells during Cholera Epidemics as Exemplified in the Town of Midnapore, Bengal: III.-The Epidemic of 1895. PMID- 29002530 TI - Obstetrics and Gynaecology-Bone-Marrow in Osteomalacia-Obstetric Teaching Congenital Teeth-Vaginal Tablets. PMID- 29002529 TI - Cholera and Its Treatment by Preventive Inoculation in the Darbhanga Jail. PMID- 29002531 TI - Soloids of Compressed Antiseptics. PMID- 29002532 TI - Potato Scurvy. PMID- 29002533 TI - Results of Anticholera Inoculations in Cachar. PMID- 29002535 TI - Kala Azar. PMID- 29002534 TI - Medicine-Thymol Treatment of Anchylostomiasis-Salicylic Acid in Rheumatism Salicylate of Methyl-Cimicifuga Racemosa-Thyroidin in Obesity-Guaiacol as an Anaesthetic-Diagnosis of Diabetes. PMID- 29002536 TI - Service Notes. PMID- 29002537 TI - The Boiling of Water. PMID- 29002538 TI - Medical News. PMID- 29002539 TI - The Etiological Relations of Cholera. PMID- 29002540 TI - Dr. Manson's Mosquito-Malaria Theory. PMID- 29002541 TI - Bacteriological Analysis of Water. PMID- 29002542 TI - Apparatus for the Medication of the Middle Ear. PMID- 29002543 TI - London Letter. PMID- 29002545 TI - The Transmission of Leprosy. PMID- 29002544 TI - Directions for the Use of Permanganate of Potassium in Combating Water-Borne Diseases. PMID- 29002546 TI - Susceptibility to Vaccination. PMID- 29002547 TI - A Case of Injury to the Abdominal Wall. PMID- 29002548 TI - Vital Statistics and Sanitation. PMID- 29002549 TI - Notes on Sanitation in Barracks and on the March in India. PMID- 29002550 TI - Medicine-Action of Tobacco-Treatment of Typhoid Fever-Tinea Versicolor-Iodide of Mercury Haemol. PMID- 29002551 TI - Venesection in Opium Poisoning. PMID- 29002552 TI - London Letter. PMID- 29002553 TI - Bangalore Sanitation. PMID- 29002554 TI - A Case of Ovarian Dropsy: Ovariotomy-Recovery. PMID- 29002555 TI - Appointments, Leave, Acknowledgments, &c. PMID- 29002556 TI - Service Notes. PMID- 29002557 TI - Obstetrics and Gynaecology-Operation for Anteflexion-Placenta Praevia-Ophthalmia Neonatorum. PMID- 29002558 TI - Radical Cure of Hydrocele. PMID- 29002559 TI - Operative Treatment of Haemorrhoids. PMID- 29002560 TI - Medical News. PMID- 29002561 TI - Selections from French Journals-Cholecystostomy-X Rays-A Diverticulum of the Bladder-Inguinal Cystocele. PMID- 29002563 TI - Kala Azar. PMID- 29002562 TI - Surgery-Surgical Shock-Peritoneal Tuberculosis-Intraperitoneal Treatment of Abdominal Hydatids. PMID- 29002564 TI - Cholera Puzzle. PMID- 29002565 TI - Vaccine Produced by Passing the Virus of Small-Pox through the Cow and Calf. PMID- 29002566 TI - The Disinfection of Wells during Cholera Epidemics as Exemplified in the Town of Midnapore, Bengal. PMID- 29002567 TI - Technique of Haffkine's Anticholera Inoculations. PMID- 29002568 TI - Transactions of Medical Societies. PMID- 29002569 TI - Some Practical Points Respecting the Malaria-Parasite. PMID- 29002570 TI - Cholera Antitoxine. PMID- 29002571 TI - A Lecture on Vaccination against Cholera: Delivered in the Examination Hall of the Conjoint Board of the Royal Colleges of Physicians of London and Surgeons of England, December 18th, 1895. PMID- 29002572 TI - Vital Statistics and Sanitation. PMID- 29002573 TI - Description of a Cheap, Easily Improvised and Portable Bacteriological Apparatus. PMID- 29002574 TI - Appointments, Leave, Acknowledgments, &c. PMID- 29002576 TI - Sanitation in Burdwan. PMID- 29002575 TI - Anchylostomiasis: Replies to Criticisms and Objections. PMID- 29002577 TI - The Anatomical Rooms in the Medical College. PMID- 29002578 TI - The Tea-Kettle Policy in Cholera. PMID- 29002579 TI - On a New Rhinoplastic Operation. PMID- 29002580 TI - A Case of "Phlegmasia Alba" Dolens in a Young Virgin. PMID- 29002581 TI - Antivenene: A Hint to Collectors of Snake-Poison. PMID- 29002582 TI - Unusual Cases of Vesical Calculus. PMID- 29002583 TI - Obstetrics and Gynaecology-The Prevention of Puerperal Fever in Private Practice Missed Labour-Icterus Neonatorum - A Special Milk for Infants-Placenta Circumvallata-Post-Mortem Caesarean Section - Mittleschmerz-Dr. Haultain Observations Respecting the Influence of Epidemic Influenza upon the Female Sexual Organs-Induction of Premature Labour in the Latter Months of Pregnancy. PMID- 29002584 TI - Pneumonia, Its Forms, Course and Results and Prevalence in the District of Pachbadra. PMID- 29002585 TI - Cases Illustrating an Unusual Susceptibility to Vaccination. PMID- 29002586 TI - Dissecting and Surgical Dressers. PMID- 29002587 TI - Medicine-Anhalonium Lewinii-Mescal Buttons-Izal as a Disinfectant and Antiseptic Diastase in Dyspepsia-The Education of Deaf-Mutes - Guaiacol in Typhoid Fever. PMID- 29002589 TI - Medical News. PMID- 29002588 TI - The Treatment of Impassable Urethral Stricture. PMID- 29002590 TI - Hepatic Abscess-Treatment: Recovery. PMID- 29002591 TI - Two Years of Anti-Choleraic Inoculations: Being a Report Submitted to the Chairman of the Calcutta Corporation on July 1st, 1896. PMID- 29002593 TI - Medical News. PMID- 29002592 TI - Appointments, Leave, &c. PMID- 29002594 TI - Canine Rabies in India. PMID- 29002595 TI - Chemistry, Pharmacy and Other Allied Subjects-Resorcinol-A Delicate Test for Albumin in Urine. PMID- 29002596 TI - Notes on Hysterectomy and Ovariotomy. PMID- 29002597 TI - Transactions of Medical Society. PMID- 29002598 TI - Evolution and Disease. PMID- 29002600 TI - Vital Statistics and Sanitation. PMID- 29002599 TI - The Tea-Kettle Policy in Cholera. PMID- 29002601 TI - On "Sporadic" Cases of Cholera. PMID- 29002602 TI - The Increase of Enteric Fever in India. PMID- 29002603 TI - Extracts from French Medical Journals-Treatment of Congenital Dislocation of the Hip-X Rays-Diphoretic Paralysis after Serumtherapy - Symphysiotomy-Beneficial Effects of Intravenous Injection of Saline Solutions in Tetanus, Traumatic Haemorrhage and Peritoneal Infective Inflammation - Cases of Gastro-Enterotomy and Intestinal Resection in Which Murphy's Button Was Employed. PMID- 29002604 TI - Surgical-Hour-Glass Stomach Due to Cicatrisation of Gastric Ulcer-Closure of Arterial Wounds by Suture-Antitoxin Treatment in Diphtheria-Mustard as an Antiseptic. PMID- 29002605 TI - Extracts from German Journals-Specific Protective Property of the Enteric Bacillus. PMID- 29002606 TI - Four Cases of Yaws: With Remarks on the Importance of Recognising and Segregating Cases in India. PMID- 29002607 TI - Medicine-The TopicalTreatment of Acne-Erysipelas-Therapeutics of Aristol Tuberculosis of the Skin-Bilateral Neuritis of the Brachial Plexus after Lobar Pneumonia. PMID- 29002608 TI - Pathology and Bacteriology-The Liver in Diabetes-Lardaceous Disease and Cirrhosis of the Liver. PMID- 29002609 TI - Obstetrics and Gynaecology-Placental Tissue, Fresh and Old-The Evolution of the Surgical Treatment of the Broad Ligament Pedicle-A New Operation for Uterine Prolapse - Some Observations on the Pathology and Treatment of Adherent Placenta Eclampsia Treated by Repeated Enemata of Warm Water-A Sympathetic Ganglion in the Human Ovary and Its Influence on Menstruation and Ovulation-Plans for the Delivery of Occipito-Posterior Positions - The Effect of Symphysiotomy in Permanently Enlarging the Pelvis-Antipyrin-Salol in the Treatment of Uterine Haemorrhage - Diphtheria-Treatment of Carcinoma of the Uterus, Certain Forms of Ovarian Disease and Fibroids of the Uterus by Means of Thyroid, Parotid and Mammary Gland Therapeutics-The Technique of the Dilatation of the Perineum in Labor-The Diagnosis of Pregnancy by Microscopical Changes in the Urine - Haemorrhage from a Ruptured Graafian Follicle Simulating Haemorrage from a Ruptured Extra-Uterine Pregnancy. PMID- 29002610 TI - Hepatic Abscess: Treatment: Recovery. PMID- 29002611 TI - Case of Sunstroke: Insidious Onset and Uninterrupted Recovery. PMID- 29002612 TI - The New Anatomical Department of Aberdeen University. PMID- 29002613 TI - Drugs and Diseases. PMID- 29002615 TI - Transactions of Medical Society. PMID- 29002614 TI - Outbreak of Cholera in the District Jail, Yeotmal: Wun District. PMID- 29002616 TI - Acute Uraemia with Amaurosis Occurring in the Course of Treatment of Stricture of the Urethra. PMID- 29002617 TI - Rheumatism: Its Forms, Course, Prevalence, Treatment, and Its Etiological Relations to Peculiar Meteorological Condition and Malaria, as Treated at Pachbadra, Rajputana. PMID- 29002618 TI - Fourth Case of Ovariotomy. PMID- 29002620 TI - Medical News. PMID- 29002619 TI - A Doubtful Case of Diarrhoea. PMID- 29002621 TI - Chemistry, Pharmacy and Other Allied Subjects-Indian Hemp Constituents Guttapercha from Leaves-Antipyrin as a Poison-Anti-Choleraic Serum-Two Kinds of X Rays-Oxygen Gas as a Restorative-Pepsin Digestion-Aseptic Surgical Catgut Mercuric Cyanide in Ophthalmic Practice-Endosine in Intestinal Catarrh-Quinosol: A New Antiseptic-Malakin in Acute Rheumatism - Electric Treatment of Diabetes Mustard Oil as a Poison in Trinidad-Tuberculosis in Goats-The X Rays in Dentistry The Action of the Rontgen Rays on Certain Microbes-Diagnostic Value of the X Rays "Photographing Thought". PMID- 29002622 TI - Vital Statistics and Sanitation. PMID- 29002623 TI - The Pasteur Institute for India. PMID- 29002624 TI - Obstetrics and Gynaecology-Indications for Repair of Lacerations of the Cervix Uteri and the Proper Operations to Meet Them-Tamponing the Cervix to Check Nausea and Vomiting of Pregnancy - An Application of the X Rays to Intra-Uterine Photography-Statistics on Weight of Infants and Foetal Heart Rate-Hernia of the Ovary in an Infant with Torsion of the Pedicle - A New Method of Ligating the Umbilical Cord-Antipyrin in Infantile Diarrhoea - New Method of Treating Misplaced Uterus-Antipyrin in Labour-Lactation Atrophy of the Uterus-The Indigestion of Breast Babies-Intravenous Injections of Normal Saline Solution-A Case of Subcutaneous Emphysema Occurring during Labour. PMID- 29002626 TI - Appointments, Leave, &c. PMID- 29002625 TI - Annual Report of the Sanitary Commissioner for Bengal, 1895. PMID- 29002628 TI - Medicine-Stethoscopic Percussion-Tic de Salaam-Sulfonal in Enuresis-Thiosinamine Oleo-Stearate of Zinc-Calcium Chloride in Pruritus-Salicylate of Sodium and Bromide of Potassium in the Irritable Temper of Gout and Cardiac Disease-Resorcin in Skin Disease. PMID- 29002627 TI - Removal of Large Vesical Calculus by Litholapaxy. PMID- 29002629 TI - The Evolution-Past and Prospective-Of Medical and Sanitary Work in India. PMID- 29002630 TI - Supplement to the Indian Medical Gazette, January 1896. PMID- 29002631 TI - Surgical Extracts-Trephining for Tubercular Meningitis-A Variation in the Technique of Major Amputations-Pseudo-Chancre-A Deodoriser for Iodoform. PMID- 29002632 TI - The Incineration of Refuse. PMID- 29002633 TI - The Mortality in Jails of Bengal. PMID- 29002634 TI - Medicine-Remittent Fever in Mekong-Yellow Fever and Its Treatment-Bile as a Culture Medium-Treatment of Liver Abscess-Suicide in Old Age-Antipyrine Erythema Codeine in the Treatment of the Morphine Habit-Permanganate of Potassium in Opium Poisoning-The Prevention of Asiatic Cholera-Chloride of Calcium in Haemophilia The Absence of the First Sound of the Heart in Typhoid Fever-Vaccination of School Children-Suicide and the Law. PMID- 29002635 TI - Obstetrics and Gynaecology-Breech Presentation-Rupture of Child's Perineum by Midwife-Version in Dorso-Posterior Position-The Treatment of Purulent Ophthalmia in New-BornChildren-On the Line of Action to Be Adopted in the Case of a Woman Who Is about to Die, Whilst Yet Undelivered. PMID- 29002636 TI - Notes on Dr. Haffkine's Anti-Cholera Inoculations in Assam, Cachar and Sylhet from October 1894 to July 1895. PMID- 29002637 TI - Relationship of Crime to Insanity and Head-Measurement with Special Reference to Criminal Responsibility. PMID- 29002638 TI - Pathology and Bacteriology-The Immediate Preservation of Post-Mortem Specimens. PMID- 29002639 TI - Anchylostomiasis. PMID- 29002641 TI - Vital Statistics and Sanitation. PMID- 29002640 TI - Notes of Some Cases of Surgical Practice at the Civil Hospital, Gaya, in 1894: Litholapaxy in Children. PMID- 29002642 TI - Transactions of Medical Societies. PMID- 29002643 TI - A Note on External Applications of Creasote in the Treatment of Malarial Intermittent Fevers. PMID- 29002644 TI - Medical News. PMID- 29002645 TI - Certain Facts Regarding the Poison-Lore of the Hindus. PMID- 29002646 TI - Action of Hydrobromate of Scopolamine upon the Iris and Ciliary Muscle-Hypnotic Anaesthesia-Turck's Gyromele in the Diagnosis and Treatment of Diseases of the Stomach-Europhen-A Simple Remedy for Enuresis. PMID- 29002647 TI - Cataract Cases. PMID- 29002648 TI - Albuminuria and Eclampsia-Calcium Carbide in the Treatment of Uterine Cancer Intra-Uterine Infection of Syphilis-Treatment of Retro-Diviation of the Uterus Management of Pelvic Presentations-Suturing Abdominal Wounds without Buried Sutures to Prevent Ventral Hernia-Presentation of the Foetal Head-Puerperal Convulsions in Twin Sisters-Ovarian Pregnancy-New Method of Inducing Abortion. PMID- 29002649 TI - Transactions of Medical Societies. PMID- 29002650 TI - The Presidency General Hospital. PMID- 29002651 TI - Appointments, Leave, &c. PMID- 29002652 TI - An Appeal to Our Countrymen. PMID- 29002653 TI - Increase of Enteric Fever in India. PMID- 29002654 TI - A Brief Historical Sketch of the Parasite of Malaria. PMID- 29002655 TI - Erratum: Disinfection of Wells. AB - [This corrects the article on p. 202 in vol. 31.]. PMID- 29002657 TI - The Preservation of Animal Lymph, Vaseline or Lanoline. PMID- 29002656 TI - Suggestion for the Prevention of Atropism. PMID- 29002658 TI - Cajeput Oil in Pneumonia, with Cases. PMID- 29002659 TI - Extract from an Account of Experiments for the Preservation of Animal Lymph Conducted. PMID- 29002660 TI - Surgical Extracts. PMID- 29002661 TI - Hydatid Diseases. PMID- 29002662 TI - Distribution and Life History of Dochmius Duodenalis. PMID- 29002663 TI - Two Cases of Sub-Hyaloid Haemorrhage. PMID- 29002664 TI - The First Case of Plague in Howrah. PMID- 29002665 TI - Vital Statistics and Sanitation. PMID- 29002666 TI - Medical News. PMID- 29002667 TI - Some Observations on the Proper Cooking of Dals (Indian Pulses). PMID- 29002669 TI - The Plague. PMID- 29002668 TI - Dr. Maclagan on Rheumatism. PMID- 29002670 TI - Note on a Case of Congenital Malformation. PMID- 29002671 TI - Main Dispensary, Sambalpore. Case of Preternatural Anus. PMID- 29002672 TI - An Account of the Production of Vaccine in India, by Passing Small-Pox Virus through the Calf. PMID- 29002673 TI - Notes on Three Cases of Intestinal Obstruction Treated by Dr. Charles by Enterotomy, Reported by Asst.-Surgn. Sushil Chandra Bhattacharya: Read at the November Meeting of the Calcutta Medical Society. PMID- 29002674 TI - Case of Traumatic Tetanus Treated with Antitoxin Unsuccessfully. PMID- 29002675 TI - Case of Tubal Foetation: Laparotomy. PMID- 29002677 TI - Vital Statistics and Sanitation. PMID- 29002676 TI - Kala Azar. PMID- 29002678 TI - Meteorology and Cholera. PMID- 29002679 TI - Medical News. PMID- 29002680 TI - Case of Compound Comminuted and Depressed Fracture of Skull. PMID- 29002681 TI - The High Mortality of Bengal Jails. PMID- 29002682 TI - Native Methods of Treating Diseases of the Eye. PMID- 29002683 TI - Pestis Ambulans. PMID- 29002684 TI - Pestis Ambulans. PMID- 29002685 TI - Irrigation of the Anterior Chamber in Operations on the Eye. PMID- 29002686 TI - Case of Bullet Wound. PMID- 29002688 TI - Case of Hydatid Cyst in a Native of India. PMID- 29002687 TI - Anchylostomum Duodenale. PMID- 29002689 TI - Technique of Haffkine's Method of Preparing Fixed Cholera Vaccine. PMID- 29002690 TI - Apenta Water-Graves' Disease-Meat Poisoning-American Pediatric Society's Collective Investigation. PMID- 29002691 TI - Bubonic Plague at Bombay. PMID- 29002692 TI - The Extra Pension and Administrative Medical Officers. PMID- 29002693 TI - Transactions of Medical Society. PMID- 29002694 TI - Medical News. PMID- 29002695 TI - Vaccination in the Punjab and Vaseline Paste Lymph. PMID- 29002696 TI - Price Memorial Fund. PMID- 29002697 TI - Reply to Brig.-Surgn.-Lieut.-Col. Sanders' Impeachment of the Anti-Choleraic Statistics in Calcutta and Serampur. PMID- 29002699 TI - Proposed International Congress for the Suppression of Leprosy. PMID- 29002698 TI - Suppurating Hydatid Cyst of Liver. PMID- 29002700 TI - Leprosy. PMID- 29002701 TI - The Best Way of Vaccinating. PMID- 29002702 TI - Anti-Cholera Inoculation. PMID- 29002703 TI - The British Medical Association at Carlisle. PMID- 29002704 TI - Surgn.-Lieut.-Col. Lawrie and the Parasite of Malaria. PMID- 29002705 TI - Main Dispensary, Sambalpur Cases. PMID- 29002706 TI - Anti-Syphilitic Serum. PMID- 29002707 TI - Controllable Disease in the Army. PMID- 29002708 TI - Criticism on the Cholera Inoculation at Calcutta and Serampur: Speech at the Municipal Meeting. PMID- 29002709 TI - Extracts from French Medical Journals. PMID- 29002710 TI - The Test for the Cholera Microbe. PMID- 29002711 TI - Specific for Dysentery. PMID- 29002712 TI - Vital Statistics and Sanitation. PMID- 29002713 TI - The Radical Cure of Hydrocele of the Tunica Vaginalis by Excision of the Sac: 126 Cases. PMID- 29002714 TI - Appointments, Leave, &c. PMID- 29002715 TI - Chemistry, Pharmacy and Other Allied Sciences-Iodoform-Vasogene in Suppurations Tincture of Horse-Chestnut for Haemorrhoids - Resorcin-Dermatology - Malakin as an Anthelmintic-Glycerine in Hepatic Colic-Eucane in Dentistry-Narcotine in Malaria. PMID- 29002716 TI - Medicine-Scurvy-Lycopersicum Cardiopathia-The Superiority of Thiol to Ichthyol. PMID- 29002717 TI - Surgn.-Major Ross' Paper on Lawrie's Discoveries. PMID- 29002718 TI - Surgical Extracts-A Modification of Trendlelenburg's Operation for Varicose Veins Surgical Operations upon Diabetic Patients. PMID- 29002719 TI - The Presidency General Hospital of Calcutta. PMID- 29002720 TI - Dysentery in Bengal Jails. PMID- 29002721 TI - Serum Treatment against Rabies. PMID- 29002723 TI - Vital Statistics and Sanitation. PMID- 29002722 TI - A Report on the Epidemic of Bubonic Plague at Hongkong in the Year 1896. PMID- 29002724 TI - Medicine. PMID- 29002725 TI - Adipocere in India. PMID- 29002726 TI - Preternatural Labor. PMID- 29002727 TI - The Indian Medical Gazette. PMID- 29002728 TI - Appointments, Leave, &c. PMID- 29002730 TI - Medical News. PMID- 29002729 TI - Notes on Some Cases of Malaria Amoeba Coli and Cercomonas. PMID- 29002732 TI - Medical Registration. PMID- 29002731 TI - Obstetrics and Gynaecology. PMID- 29002733 TI - Some Suggestions as to the Treatment and After-Treatment of Cataract Derived from an Experience of 1,100 Cases. PMID- 29002734 TI - The Human Factor in the Spread of Plague and the Lesson It Teaches. PMID- 29002735 TI - Notes on the Spread of the Plague in Bombay. PMID- 29002736 TI - Transactions of Medical Societies. PMID- 29002737 TI - Ligature of the External Iliac for Elephantiasis. PMID- 29002739 TI - Appointments, Leave, &c. PMID- 29002738 TI - Chronic Extra-Dural Cerebral Abscess-Operation: Recovery. PMID- 29002740 TI - Tropical Intermittent Fevers. PMID- 29002741 TI - A Successful Case of Ovariotomy. PMID- 29002742 TI - Calf Vaccination in Prussia. PMID- 29002743 TI - The Wedge Operation for Entropion and Trichiasis. PMID- 29002744 TI - Medicine: Examination of Eyes in the Public Schools of Baltimore-Sub-Conjunctival Injections in the Treatment of Certain Diseases of the Eye-Medico-Legal Aspect of Eye and Ear Cases-Treatment of Optic Nerve Atrophy by Mercurial Inunctions in Conjunction with the Hot Baths of the Hot Springs of Arkansas-Blennostasine-A Physical Sign of the Rheumatic Diathesis-Treatment of Sciatica by Massage Corsican Fever-Simple Method for the Detection of Lead in Organic Fluids. PMID- 29002745 TI - Lord Sandhurst's Measures against Plague. PMID- 29002746 TI - Memorandum on the Use of a Saturated Solution of Common Salt as a Preservative for Viscera Sent for Chemical Examination. PMID- 29002747 TI - Vivisection (So-Called): Its Role in the Service of Man and Beast. PMID- 29002748 TI - Precautions against Plague. PMID- 29002749 TI - Cholera Diffusion by Flies. PMID- 29002750 TI - The Epidemic of Bubonic Plague in Hongkong, 1894. PMID- 29002752 TI - Vital Statistics and Sanitation. PMID- 29002751 TI - Enteric Fever in Rangoon, and Its Rational Treatment. PMID- 29002754 TI - M. Haffkine. PMID- 29002753 TI - The Malarial Parasite. PMID- 29002755 TI - Medical News. PMID- 29002756 TI - Obstetrics and Gynaecology: Treatment of Eclampsia-Secondary Abdominal Pregnancy. PMID- 29002757 TI - An Account of the Production of Vaccine in India by Passing Small-Pox Virus through the Calf. PMID- 29002758 TI - The Epidemic of Bubonic Plague in Hongkong, 1894. PMID- 29002759 TI - Agar-Agar. PMID- 29002760 TI - Transactions of Medical Societies. PMID- 29002761 TI - The Howrah Case. PMID- 29002762 TI - Aryan Medical Science. PMID- 29002764 TI - Vital Statistics and Sanitation. PMID- 29002763 TI - Obstetrics and Gynaecology: Deciduoma Malignum-Ovarian Dermoids-Methyl Blue in Inoperable Cancer-Ovarian Therapy-Contribution to the Study of Ovulation, Menstruation and Conception-Position of the Normal Ovary-Physiology of Menstruation. PMID- 29002766 TI - London Letter. PMID- 29002765 TI - Increase of Enteric Fever. PMID- 29002767 TI - Appointments, Leave, &c. PMID- 29002768 TI - Kala Azar. PMID- 29002769 TI - Medicine: Kebler on Poisonous Honey-Proben on Pilocarpine in the Uraemia of Brights' Disease-Babcock on Treatment of Haemoptysis-Herrick on Thyroid Therapy McEwen on Chloroform Narcosis-Eskridge on Comparative Temperature on Each Side of the Body in Cerebral Lesions. PMID- 29002770 TI - Imperforate Hymen and Retained Menses. PMID- 29002771 TI - The Disinfection of the Skin in Surgical Operation. PMID- 29002772 TI - Hydatid Cysts. PMID- 29002773 TI - The Medical Board and Plague in Calcutta. PMID- 29002774 TI - Notes on an Unusual Case. PMID- 29002775 TI - The Treatment of Granular Ophthalmia and Its Complications in Southern India. PMID- 29002776 TI - Medical News. PMID- 29002777 TI - Pressure in the Pregnant Uterus-Deciduoma Malignum - Non-Ligation of the Umbilical Cord-Electricity in Obstetrics. PMID- 29002778 TI - Appointments, Leave, &c. PMID- 29002780 TI - Vital Statistics and Sanitation. PMID- 29002779 TI - Medical News. PMID- 29002782 TI - Hospital Nursing in Calcutta. PMID- 29002781 TI - New Bye-Laws on House Sanitation in Bangalore. PMID- 29002783 TI - Transactions of Medical Societies. PMID- 29002784 TI - Plague in Bombay. PMID- 29002785 TI - Notes on Stone in the Bladder. PMID- 29002786 TI - Has Adipocere Been Observed in India. PMID- 29002787 TI - Report on Plague. PMID- 29002788 TI - Malaria and Immunity. PMID- 29002789 TI - Enteric Fever in Rangoon, and Its Rational Treatment. PMID- 29002790 TI - Epithelial Xerosis in Natives of India. PMID- 29002791 TI - Use of Camphoric Acid in Excessive Sweating. On a Special Tract in the Lateral Limiting Layer of the Spinal Cord - Malignant Disease of the Stomach-The Internal Secretions of the Thyroid and Suprarenal Glands. PMID- 29002792 TI - A Case of Hyperaemia of the Ovary. PMID- 29002793 TI - Extracts from French Journals-A Case of Alcaptonuria. PMID- 29002795 TI - Report on the Working of the Charitable Dispensaries in Bengal, 1893-95. PMID- 29002794 TI - The Howrah Case. PMID- 29002796 TI - Medical News. PMID- 29002797 TI - Experimental Investigations on Protective Inoculation of Men against Typhus Abdominalis. PMID- 29002798 TI - The Medical Board of Calcutta. PMID- 29002799 TI - Plague in Bombay. PMID- 29002801 TI - Vital Statistics and Sanitation. PMID- 29002800 TI - Preservation of Vaccine Lymph. PMID- 29002802 TI - Eucain in Ophthalmic Surgery. PMID- 29002803 TI - Medicine: Anhelonium Lewinii-Glenard's Disease, or Enteroptosis-Sparteine Sulphate and Chloroform-Uraemic Dyspnoea-Chloride of Ammonium in Delirium Tremens Electro Diagnosis and Electro-Therapeutics Simplified -Salol in Diarrhoea. PMID- 29002804 TI - Appointments, Leave, &c. PMID- 29002806 TI - London Letter. PMID- 29002807 TI - Ligature of the External Iliac Artery for Elephantiasis. PMID- 29002805 TI - Obstetrics and Gynaecology: Post-Partum Haemorrhage-Intravenous Injections of Saline Solution in Puerperal Eclampsia-Best Method of Suture after Laparotomy-Non Draining Gauze Tampons in the Treatment of Post-Partum Haemorrhage-The First Ovariotomy. PMID- 29002808 TI - The Epidemic of Bubonic Plague in Hongkong, 1894. PMID- 29002809 TI - A Case of Hepatic Abscess: Operation and Recovery. PMID- 29002810 TI - List of Medical Officers and Guests Present at the I.M.S. Dinner. PMID- 29002811 TI - Plague Precautions in Bengal. PMID- 29002812 TI - The Value of Exploratory Laparotomy Per Se in (a) Real, and (b) Supposed Malignant Disease of the Abdominal Organs-Delayed Expulsion of Second Twin Camphorasan Antigolactagogue-A Simple Method of Treating Post-Partum Haemorrhage from Atony of the Uterus. PMID- 29002813 TI - Some Suggestions as to the Treatment and after Treatment of Cataract Derived from an Experience of 1,100 Cases. PMID- 29002814 TI - Ligature of the External Iliac Artery for Elephantiasis. PMID- 29002815 TI - Medical News. PMID- 29002817 TI - Urticaria. PMID- 29002816 TI - A Report on the Epidemic of Bubonic Plague at Hongkong in the Year 1896. PMID- 29002819 TI - Notes on Stone in the Bladder. PMID- 29002818 TI - A Case of Congenital Deformity. PMID- 29002820 TI - London Letter. PMID- 29002821 TI - Appointments, Leave, &c. PMID- 29002823 TI - I. M. S. Dinner in London. PMID- 29002822 TI - A Case of Chancre of the Eyelid. PMID- 29002824 TI - What Should Midwives Be Taught? PMID- 29002826 TI - Vital Statistics and Sanitation. PMID- 29002825 TI - The So-Called Kala-Azar of Assam. PMID- 29002827 TI - Use and Abuse of Ergot in Obstetrics. PMID- 29002828 TI - The Infiltration (Schleich) Method for Producing Local Anaesthesia. PMID- 29002829 TI - Transactions of Medical Societies. PMID- 29002832 TI - The Organisation of the Military Medical Services. PMID- 29002830 TI - Case of Umbilical Hernia, without a Sac or Other Covering, Complicated by Intussusception and Perforation of the Bowel. PMID- 29002833 TI - The Plague Campaign. PMID- 29002831 TI - Spelling of Ankylostoma. PMID- 29002835 TI - Elephantiasis. PMID- 29002834 TI - Large Urethral Calculus. PMID- 29002837 TI - Two Cases of Coloboma Iridis in Mother and Son, with Monocular Policoria Also in the Son. PMID- 29002836 TI - On the Comparative Value and Cost of Disinfectants. PMID- 29002838 TI - Kala-Azar and Diseases Confused with It. PMID- 29002839 TI - Medicine: Anaesthetic Leprosy Non-Contagious-Iced Drinks and Dyspepsia-Taka Diastase as a Digestive Agent-Thymol as a Vermifuge - Appendicitis as a Medical Disease - Herpes in Malarial Fevers-Toxic Sweat and Prickly-Heat-An Emergent Army Ration - Syphilis and Locomotor Ataxy in Negroes-The Malarial Hand-Cretinism Treated by Thyroid Extract-Splenectomy-Conjugal Diabetes and the Theory of Contagion. PMID- 29002840 TI - Remarks on Yersin's Serum in Plague. PMID- 29002841 TI - London Letter. PMID- 29002842 TI - Special Senses: Toxic Amblyopia-Otitic Brain Disease. PMID- 29002843 TI - Appointments, Transfers, Leave, &c. PMID- 29002845 TI - Medical News. PMID- 29002844 TI - Is Yaws Syphilis? PMID- 29002846 TI - Case of Abscess of the Liver of Long Standing Which Opened into the Lung: Subsequent Operation and Death from Multiple Abscess. PMID- 29002847 TI - Abstract Report on Gunshot Wounds Received in the Attack on the Malakand and in the Operations Immediately Following, and Which Were Transferred for Treatment to the Base Hospital, Nowshera. PMID- 29002848 TI - Obstetrics and Gynaecology: Ovariine - Vesical Calculus after Caesarean Section Hysterectomy in a Child Nine Months Old-Precocious Menstruation-The Anticipation of Post-Partum Haemorrhage-Plural Pregnancies. PMID- 29002849 TI - A Clinical Lecture on Tetanus. PMID- 29002850 TI - Rupture of the Heart by a Blow with a Stick : Survival for over Three Hours. PMID- 29002851 TI - Service Note. PMID- 29002853 TI - Medical News. PMID- 29002852 TI - Obstetrics and Gynaecology: On Posterior-Occipital Positions of the Foetal Head - Diagnosis and Treatment of Rupture of the Uterus-Abortion and Quinine-Eclampsia. PMID- 29002854 TI - Plague and House Disinfection. PMID- 29002855 TI - Some Curiosities in Comma Bacilli of Asiatic Cholera. PMID- 29002856 TI - Medicine: Diabetes Mellitus and Lesions of the Pancreas-Accurate Diagnosis of Diseases of the Chest-Results of Haffkine's Anti-Cholera Inoculations in India - Carbolic Acid Poisoning - Malarial Haematuria - Simplicity and Palatability in Prescribing. PMID- 29002857 TI - Cases at the St. Stephen's Mission Hospital, Delhi: Cases of Dystocia Due to Monsters, &c. PMID- 29002858 TI - Complications in the After-Treatment of Cases of Cataract Extraction. PMID- 29002859 TI - The So-Called Kala-Azar of Assam. PMID- 29002861 TI - Leave and the Indian Medical Service. PMID- 29002860 TI - Abdominal Surgery at the Eden Hospital. PMID- 29002862 TI - Vital Statistics and Sanitation. PMID- 29002863 TI - The Pasteur-Chamberland System of Filtration at the Darjeeling Water-Works. PMID- 29002864 TI - Appointments, Leave, &c. PMID- 29002865 TI - Three Cases of Empyema Suggestive of an Infectious Nature. PMID- 29002867 TI - Transactions of Medical Societies. PMID- 29002866 TI - London Letter. PMID- 29002869 TI - Medical News. PMID- 29002868 TI - Drowning in Shallow Water. PMID- 29002870 TI - Drugs and Appliances. PMID- 29002871 TI - Fracture of Patella by a Surgeon during Forcible Flexion. PMID- 29002873 TI - Appointments - Transfers-Leave, &c. PMID- 29002872 TI - 28,000 Heights and Weights. PMID- 29002874 TI - Service Notes. PMID- 29002875 TI - Indian Army Nursing Service. PMID- 29002876 TI - Medicine: Enteric Fever Amongst Natives of India-Beri-Beri-Spinal Irritation Angina Pectoris-Rheumatoid Arthritis-Chronic Urticaria-Morphinism-Night Sweats. PMID- 29002877 TI - The "Indian Medical Gazette". PMID- 29002878 TI - A Note on Melanoglossia. PMID- 29002879 TI - Permanganate Disinfection of Village Wells in Epidemics of Dysentery and Diarrhoea. PMID- 29002880 TI - A Case of Quinine Eruption. PMID- 29002881 TI - A Median Incisor Tooth. PMID- 29002882 TI - Hepatic Abscess. PMID- 29002883 TI - Elephantiasis in Ceylon: Its Prevalence in Villages near the Swampy Ground of Old Abandoned Tanks. PMID- 29002885 TI - Sanitation in Srinagar. PMID- 29002884 TI - Is Yaws Syphilis?: Replies to Mr. Hutchinson's Questions. PMID- 29002886 TI - Dr. W. J. Simpson. PMID- 29002887 TI - Transactions of Medical Societies. PMID- 29002888 TI - Vital Statistics and Sanitation. PMID- 29002889 TI - Cinchona Culture and Quinine Production. PMID- 29002890 TI - Quinine Exanthemata. PMID- 29002891 TI - Public Health. PMID- 29002892 TI - Some Remarks on the Position of Certain Remittent Fevers Hitherto Frequently Classed as Malarial, with Illustrative Cases and Temperature Charts. PMID- 29002894 TI - London Letter. PMID- 29002893 TI - Abdominal Surgery at Darbhanga in 1896. PMID- 29002896 TI - Abstract of Remarks by Surgn.-Col. A. Stephen, M.B., Principal Medical Officer and Sanitary Commissioner, Assam, on Dr. Rogers' Report on Kala-Azar. PMID- 29002895 TI - Central Asylums for Lunatics. PMID- 29002898 TI - The Scientific Study of Preventive Medicine in India. PMID- 29002897 TI - Medicine: Tropical Abscess of Liver-Pneumonia-Appendicitis-The Parasites of Malaria-Malaria in Animals-Is Diabetes Increasing?-Infection by Flies. PMID- 29002899 TI - The Lower Bengal (Burdwan) Epidemic Fever Reviewed and Compared with the Present Assam Epidemic Malarial Fever (Kala-Azar). PMID- 29002901 TI - Surgery: A Contribution to the Study of Anastomosis of the Hollow Viscera-A Modified Murphy Button-Some Methods of Healing Granulating Surfaces-Irrigation in Intussusception-A New Throat Spray. PMID- 29002900 TI - Can Typhoid Fever Be Aborted? PMID- 29002902 TI - Medical News. PMID- 29002903 TI - Appointments, Transfers, Leave, &c. PMID- 29002904 TI - Service Notes. PMID- 29002905 TI - The Larymore Boiler. PMID- 29002906 TI - Vital Statistics and Sanitation. PMID- 29002907 TI - A Suggested Improvement in "Surahis". PMID- 29002908 TI - Obstetrics and Gynaecology: Uterine Haemorrhages and Ruptures of the Circular Sinus-The Treatment of After-Pains-Indications of Symphyseotomy-A Case of Symphyseotomy-Treatment of Asphyxia Neonatorum-Ovarian Tumours-The Prevention of Thirst after Abdominal Operations-Caesarian Section-Abdominal Surgery-Shock during Abdominal Operations. PMID- 29002910 TI - Vital Statistics and Sanitation. PMID- 29002909 TI - Abdominal Surgery at Darbhanga in 1896. PMID- 29002912 TI - Abdominal Surgery at the Eden Hospital, Calcutta: During the Years 1894, 1895 and 1896. PMID- 29002911 TI - An Improved Pattern of "Giant" Lithotrite. PMID- 29002913 TI - Appointments, Leave, &c. PMID- 29002914 TI - Is Perforation Justifiable in Delay of Delivery of the After-Coming Head? PMID- 29002915 TI - Prevention of Malaria. PMID- 29002916 TI - Report on the Sanitary Administration of the Punjab for 1896. PMID- 29002917 TI - A Case of Gastro-Intestinal Catarrh: Speedy and Unexpected Recovery. PMID- 29002918 TI - Cholera Cases in Gaya. PMID- 29002919 TI - Medicine: Quarantine versus Medical Inspection-An Example of Quarantine before the Late Venice Conference-The Causation and Rhythm of the "Presystolic" Murmur Practical Conclusions Derived from a Study of Five Hundred Cases of Cardiac Disease-Cancer of the Stomach in Early Life-Cancer of the Breast in a Child. PMID- 29002920 TI - Cases of Undiagnosed Liver Abscess. PMID- 29002922 TI - The Health of Prisoners. PMID- 29002921 TI - Medical News. PMID- 29002923 TI - Transactions of Medical Societies. PMID- 29002924 TI - The Mortality of Operations in the Medical College Hospital, Calcutta. PMID- 29002925 TI - Typhoid Bacilli and the Blood Test. PMID- 29002926 TI - Enteric Fever in Rangoon. PMID- 29002927 TI - Obstetrics and Gynaecology: Subcutaneous Symphysiotomy-A Case of Intra-Peritoneal Gestation at Term-Age of Foetus in Miscarriages-Axis of the Foetal Head. PMID- 29002928 TI - Peculiar Pigmented Cells Found in Two Mosquitoes Fed on Malarial Blood. PMID- 29002929 TI - On the Difference between Serum and Blood Solutions, the Condition of the Test Culture and the Significance of Bacterium Coli Infection in Relation to Typhoid Diagnosis. PMID- 29002930 TI - Dysentery in Bengal Jails. PMID- 29002931 TI - Transactions of Medical Societies. PMID- 29002933 TI - The Building Commission for Calcutta. PMID- 29002932 TI - A Successful Case of Ovariotomy. PMID- 29002934 TI - The Plague Prophylactic. PMID- 29002935 TI - Appointments, Leave, &c. PMID- 29002936 TI - Remarks on the Pathology of Plague. PMID- 29002937 TI - Methods of Malarial Infection. PMID- 29002938 TI - Kola during Labour-Prevention and Treatment of Puerperal Fever-Guaiacol in Puerperal Eclampsia-The Anatomy and Development of the Human Placenta. PMID- 29002939 TI - Cases of Undiagnosed Liver Abscess. PMID- 29002940 TI - The So-Called Kala-Azar of Assam. PMID- 29002941 TI - Contributions to the Knowledge of the Placenta and the Maternal Structures Entering into the Formation of the Foetal Membranes. PMID- 29002942 TI - Administration of the Presidency General Hospital. PMID- 29002943 TI - Appendicitis from a Physician's Point of View-Percussion and Palpation-Treatment of Tuberculosis. PMID- 29002944 TI - Plague in India. PMID- 29002945 TI - Vital Statistics and Sanitation. PMID- 29002947 TI - Medical News. PMID- 29002946 TI - A Case of Peritonitis Caused by Perforation of the Small Intestine by the Stalk of an Egg-Plant Fruit and Resulting in Death. PMID- 29002948 TI - A Report on the Epidemic of Bubonic Plague at Hongkong in the Year 1896. PMID- 29002949 TI - Treatment of Epilepsy-Epilepsy and Eye Strain-Treatment of Insanity by Hypnotic Suggestion. PMID- 29002951 TI - M'Keown's Method of Irrigation in Cataract Operation. PMID- 29002952 TI - Colonel Thomas Holbein Hendley, C.I.E., I.M.S. PMID- 29002950 TI - Paper on Slabs of the Abdomen. PMID- 29002953 TI - Cholera in the District of Puri, with a Special Account of the Epidemic during the Year 1901. PMID- 29002954 TI - Gleanings from the Atte Della Societa Per Gli Studi Della Malaria, Vol. III. PMID- 29002955 TI - The Mechanical Destruction of Bacilli. PMID- 29002956 TI - The Oyster Scare. PMID- 29002957 TI - Tubercle of Lungs in Bengal Jails. PMID- 29002958 TI - The Pathology, Prevention and Treatment of Malignant Disease. PMID- 29002959 TI - Mr. Jonathan Hutchinson on Leprosy. PMID- 29002960 TI - Shellfish Poisoning. PMID- 29002961 TI - Current Topics. PMID- 29002962 TI - Service Notes. PMID- 29002963 TI - A Case of "Blastomycetic Dermatitis" in a Chitrali. PMID- 29002965 TI - The Introduction of the Antiseptic System into India. PMID- 29002964 TI - The Microbe of Rheumatism. PMID- 29002966 TI - The Lister Jubilee. PMID- 29002967 TI - Glioma of the Retina. A Lecture Delivered before the Ahmedabad Medical Society. PMID- 29002968 TI - Current Topics. PMID- 29002969 TI - Notes on a Case of Congenital Absence of Both Eyeballs. PMID- 29002970 TI - The D. P. H. and the Medical Services. PMID- 29002971 TI - Notes on Two Cases of Caesarean Section (Porro's Modification). PMID- 29002972 TI - A Case of Hernia of the Bladder Associated with Inguinal Hernia of the Same Side. PMID- 29002974 TI - The Inquiry into Lathyrism. PMID- 29002973 TI - Trypanosoma Disease in Man. PMID- 29002975 TI - Notes on the Origin of the Presidency General Hospital, Calcutta: III. Initial Steps. PMID- 29002976 TI - An Analysis of One Thousand Consecutive Cataract Extractions. PMID- 29002977 TI - Serum Treatment of Traumatic Tetanus: A Successful Case. PMID- 29002978 TI - Two Rapidly Fatal Cases of Enteric with Marked Pneumonic Symptoms from the Onset. PMID- 29002979 TI - Neurasthenia in Anglo-Indians. PMID- 29002980 TI - Note on the Bacteriology of Dysentery and the Value of the Serum Test in Its Differentiation. PMID- 29002981 TI - The Prize Essay of the Association of Military Surgeons of the United States. PMID- 29002983 TI - The Leprosy Discussion at Swansea. PMID- 29002982 TI - A Possible Cause of Kala-Azar. PMID- 29002984 TI - Notes on a Case of Pyelitis Due to the Bacillus Coli Communis. PMID- 29002985 TI - Current Topics. PMID- 29002987 TI - Post-Nasal Adenoids and Their Treatment in Australia. PMID- 29002986 TI - Infantile Paralysis. PMID- 29002989 TI - Service Notes. PMID- 29002988 TI - Notes on Continental Eye Clinics. PMID- 29002990 TI - A Case of Medico-Legal Interest. PMID- 29002992 TI - Anchylostomiasis in the United States. PMID- 29002991 TI - Malaria: As Seen in the Andamans Penal Settlement. PMID- 29002993 TI - Suicidal Hanging: Deaths from the Secondary Effects. PMID- 29002994 TI - A Case of Suicidal Hanging-Death after Nine Days. PMID- 29002995 TI - The Biological Disposal of Sewage. PMID- 29002996 TI - The Health of the District of Jessore, and How to Improve It. PMID- 29002997 TI - Cordite Eating. PMID- 29002998 TI - The Indian Medical Service. PMID- 29002999 TI - Cases from the Crossthwaite Hospital, Naini Tal. PMID- 29003001 TI - Hospital Sunday. PMID- 29003000 TI - Red Water and Rinderpest in Cattle. PMID- 29003002 TI - Diseases of Women and Children. PMID- 29003003 TI - Extracts from Medical Journals. Medicine. PMID- 29003004 TI - Service Notes. PMID- 29003005 TI - Ascaris Lumbricoides Causing Perforation of Stomach and Intestine and Death. PMID- 29003006 TI - Infant with a Caudal Appendage. PMID- 29003007 TI - Indian Milk Supply and Infective (Epidemic) Diarrhoea. PMID- 29003009 TI - Report on the Political Administration of the Territories within the Central India Agency for 1901-1902. PMID- 29003008 TI - Note on the Mycoid Body Found in the Blood Corpuscles in Remittent Fevers. PMID- 29003010 TI - A Case of Hydrophobia of Unascertained Origin. PMID- 29003011 TI - A New Desiccator for Plague Disinfection. PMID- 29003012 TI - A Case of Tetanus Treated with Tetanus Antitoxin: Recovery. PMID- 29003013 TI - Report on Sanitation, Dispensaries and Jails in Rajputana for 1901, and on Vaccination for the Year 1901-1902. PMID- 29003014 TI - Special Senses. PMID- 29003016 TI - A Case of Spontaneous Dislocation of the Head of Radius during Sleep. PMID- 29003015 TI - Transactions of Medical Societies. PMID- 29003017 TI - Fracture of the Leg: Malunion: Operation: Successful Result. PMID- 29003018 TI - A New Field-Service Dooly. PMID- 29003019 TI - Cancer. PMID- 29003020 TI - Cancer in Europe. PMID- 29003021 TI - Cataract Operations: A Correction. PMID- 29003022 TI - Current Topics. PMID- 29003024 TI - Cure of Cancer. PMID- 29003023 TI - Poisoning by Thevetia Nerifolia (Yellow Oleander). PMID- 29003025 TI - A Case of Lympho-Sarcoma of the Small Intestine. PMID- 29003026 TI - A Case of Stone Impacted in the Ureter: Operation, Recovery. PMID- 29003027 TI - A Suggestion for Plague Treatment. PMID- 29003028 TI - Current Topics. PMID- 29003029 TI - Foreign Body in the Stomach-Gastrotomy: Recovery. PMID- 29003030 TI - An Account of a Race of Idiots Found in the Punjab, Commonly Known as "Shah Daula's Mice". PMID- 29003031 TI - Extraction of Cataract in the Government Ophthalmic Hospital, Madras. PMID- 29003032 TI - Some Cases of Labour in Heart Disease. PMID- 29003034 TI - Freyer's Prostatectomies. PMID- 29003033 TI - Enteric Fever. PMID- 29003035 TI - The Journal of the Royal Army Medical Corps. PMID- 29003036 TI - Correspondence. PMID- 29003038 TI - Ennore, Boscombe, Bournemouth. PMID- 29003037 TI - Extracts from Medical Journals. Special Senses. PMID- 29003040 TI - Report on the Punjab Lunatic Asylum for 1902. PMID- 29003039 TI - A Case of Tetanus, Treated with Tetanus Antitoxine: Recovery. PMID- 29003041 TI - Surgery. PMID- 29003042 TI - Extracts from Foreign Medical Journals. PMID- 29003043 TI - Diseases of Women and Children. PMID- 29003044 TI - Ventnor. PMID- 29003045 TI - The Recent Birthday Honours. PMID- 29003046 TI - The Use of the Catheter after External Urethrotomy. PMID- 29003047 TI - Further Notes on Experiments on the Pathology and Treatment of Malignant Disease. PMID- 29003048 TI - The Cure of Cancer. PMID- 29003049 TI - A Case of Cerebral Abscess. PMID- 29003050 TI - The Use of Paraffin in Surgery. PMID- 29003052 TI - Enteric Fever in Goorkhas : With a Few Remarks as to Its Propagation and Differential Diagnosis in the Early Stage. PMID- 29003051 TI - Notes on the Origin of the Presidency General Hospital, Calcutta: IV.-Mr. Kiernander's Difficulties. PMID- 29003053 TI - Cold Water vs. Drugs. PMID- 29003055 TI - Service Notes. PMID- 29003054 TI - The Mode of Entry of Plague Infection into the Human Body. PMID- 29003056 TI - Current Topics. PMID- 29003057 TI - Another Prize Day at Netley. PMID- 29003058 TI - The Cosmopolitan Diseases in the Tropics. PMID- 29003059 TI - An Analysis of One Thousand Consecutive Cataract Extractions. PMID- 29003060 TI - Report on the Outbreak of Epidemic Dropsy in the Barisal Jail. PMID- 29003061 TI - Mr. Johnathan Hutchinson's Visit to India. PMID- 29003062 TI - Legislation against Drunkenness. PMID- 29003064 TI - Service Notes. PMID- 29003063 TI - Liver Chill as a Factor of Disease in the Tropics. PMID- 29003065 TI - The Sleeping Sickness of Uganda. PMID- 29003066 TI - The R. A. M. College. PMID- 29003067 TI - An Epidemic of Catarrhal Jaundice in Buxar Central Jail. PMID- 29003068 TI - Malaria: As Seen in the Andamans Penal Settlement. PMID- 29003069 TI - Physique. PMID- 29003070 TI - Extracts from Medical Journals-Medicine. PMID- 29003071 TI - An Attack of Gall-Stones-Collapse: Death. PMID- 29003072 TI - Surgery. PMID- 29003073 TI - Jaundice in Port Blair, Andaman Islands. PMID- 29003075 TI - A Question of Medical Ethics. PMID- 29003074 TI - Abscess of Ovary Presenting All the Signs of Ovarian Cyst. PMID- 29003076 TI - Primary Carcinoma of the Liver. PMID- 29003078 TI - Diseases of Women and Children. PMID- 29003077 TI - The Life-Span of the Guinea-Worm. PMID- 29003079 TI - On Diseases of the Liver. PMID- 29003081 TI - The Services. PMID- 29003080 TI - Four Cases of Menorrhagia Successfully Treated with Suprarenal Gland Extract. PMID- 29003083 TI - British Medical Association Meeting. July 2nd-31st, 1903. PMID- 29003082 TI - A Case of Transposition of Viscera Recognised during Life: Death from Malarial Fever: Post Mortem-Total Congenital Absence of Spleen. PMID- 29003084 TI - The Treatment of Yellow Fever. PMID- 29003085 TI - Notes on Operations for Abscess of the Liver, Ascites, and Gall-Stones. PMID- 29003086 TI - Diseases of the Liver in India. PMID- 29003087 TI - On the Physiological Action of the Hydrophidae. PMID- 29003088 TI - Note on an Unusual Complication Met with during Operation for Punctured Wound of Abdomen. PMID- 29003090 TI - Tuberculosis in Calcutta. PMID- 29003089 TI - Current Topics. PMID- 29003091 TI - Ambulatory Plague. PMID- 29003092 TI - A Case of Freyer's Operation for Enlargement of the Prostate. PMID- 29003093 TI - Antidiphtheritic Inoculation. PMID- 29003095 TI - The Tropical Diseases Section. PMID- 29003094 TI - A Case of Colloid Carcinoma of the Mesentery. PMID- 29003096 TI - The Annual Meeting of the British Medical Association. PMID- 29003097 TI - A Case of Death from Septic Duodenitis after Relief of Acute Intestimal Obstruction. PMID- 29003099 TI - Transactions of Medical Societies. PMID- 29003098 TI - A Unique Pig-Sticking Accident. PMID- 29003100 TI - Adrenalin and Its Uses in General Surgery, Especially Applied to Ophthalmology. PMID- 29003101 TI - Radio Activity. PMID- 29003102 TI - Service Notes. PMID- 29003104 TI - Disposal of City Sewage in India. PMID- 29003103 TI - A Generally Unknown Source of Enteric Fever. PMID- 29003105 TI - Old Unreduced Posterior Dislocation of the Bones of the Forearm: Excision of the Elbow Joint. PMID- 29003107 TI - A Note on Some Cases of Poisoning by Scopolia Lurida,-Atropaceae: Proceedings of the Peshawar Medical Society. PMID- 29003108 TI - A Case of Elephantiasis of the Scrotum: Operated in the Civil Hospital, Aden. PMID- 29003106 TI - Ascaris Lumbricoides. PMID- 29003109 TI - The Bhowanipur Food Poisoning. PMID- 29003110 TI - Notes from Continental Eye Clinics: IX.-Denmark. PMID- 29003111 TI - Poisoning by Antimony. PMID- 29003112 TI - Appendicitis with Abscess. PMID- 29003113 TI - Vaccination and Smallpox. PMID- 29003114 TI - Extracts from Medical Journals-Medicine. PMID- 29003116 TI - Current Topics. PMID- 29003115 TI - Perineal Litholapaxy in Children. PMID- 29003117 TI - Colopexy for Prolapsus Recti. PMID- 29003119 TI - The Seventy-First Annual Meeting of the British Medical Association. PMID- 29003118 TI - Two Cases of Rupture of the Lung of Uncertain Origin. PMID- 29003120 TI - Trypanosomiasis. PMID- 29003121 TI - Case of Meckel's Diverticulum. PMID- 29003122 TI - Leprosy. PMID- 29003123 TI - A Medical Directory for Bengal. PMID- 29003124 TI - The Bengal Branch of the Countess of Dufferin's Fund. PMID- 29003126 TI - Notes on the Mercurial Treatment of Chronic Dysentery, Cholera and Liver Complaints. PMID- 29003125 TI - Cases Illustrating Difficulties in Plague Diagnosis. PMID- 29003127 TI - Annual Report of the Sanitary Commissioner with the Government of India, 1901. PMID- 29003128 TI - The Dissemination of Enteric Fever by Dust. PMID- 29003129 TI - Note on an Abnormality of the Radial Artery. PMID- 29003130 TI - A Case of Ligature of the External Iliac Artery for Femoral Aneurism. PMID- 29003131 TI - Some Modern Views on Primary Glaucoma. PMID- 29003132 TI - Case of Strangulated Inguinal Hernia: Perforation of the Bowel: Resection of 7 Inches of Gangrenous Gut : Recovery. PMID- 29003134 TI - Time Flies. PMID- 29003133 TI - A Note on Anopheles Fuliginosus and Sporozoits. PMID- 29003136 TI - Service Notes. PMID- 29003135 TI - Demonstration of Plague Bacilli in Blood. PMID- 29003137 TI - Ligature of the Right Common Iliac Artery for Diffused Iliac Aneurism. PMID- 29003139 TI - Current Topics. PMID- 29003138 TI - A Good Hair Dye. PMID- 29003140 TI - Notes on the Early Hospitals of Calcutta. PMID- 29003141 TI - Medico-Legal Notes. PMID- 29003142 TI - A Note on Operation for Hernia. PMID- 29003143 TI - Surgeon-General Beatson on the Indian Medical Service. PMID- 29003144 TI - Utility of Saline Injections in Haemorrhage. PMID- 29003145 TI - The Furlough Pay of Majors, I.M.S. PMID- 29003146 TI - Experimental Inoculation of Malaria, with a Relapse after Eight Months. PMID- 29003148 TI - Indian Medical Service Men in the "Dictionary of National Biography". PMID- 29003147 TI - Serum Agglutination and Acute Dysentery. PMID- 29003149 TI - The First Two Hospitals in Calcutta. PMID- 29003151 TI - Service Notes. PMID- 29003150 TI - The Dose of Antitoxins. PMID- 29003152 TI - Remarks on the Differential Count of the Leucocytes in Malarial and Other Fevers of India. PMID- 29003154 TI - Annus Medicus, 1902. PMID- 29003153 TI - Case of Hernia of the Brain. PMID- 29003155 TI - Army Medical Organisation in the Field: The Sander Prize Essay. PMID- 29003156 TI - Notes on the Origin of the Presidency General Hospital, Calcutta. PMID- 29003157 TI - Cerebro-Spinal Meningitis in Burma. PMID- 29003158 TI - Yellow Fever. PMID- 29003159 TI - Imambarah Hospital, Hughli; Notes on Some Surgical Cases. PMID- 29003161 TI - Successful Operation for Cerebral Abscess. PMID- 29003160 TI - Notes from Continental Eye Clinics: VIII.-Warsaw-Moscow and St. Petersburg. PMID- 29003162 TI - Some Emergency Rations. PMID- 29003163 TI - Pathological Exotics. PMID- 29003164 TI - Notes on the Mycoid Body Found in the Blood Corpuscles in Remittent Fevers. PMID- 29003165 TI - The Flea as the Missing Link in Plague Infection. PMID- 29003166 TI - Unaccustomed Plenty and Prevalence of Bowel-Complaints in the Bengal Jails. PMID- 29003167 TI - Current Topics. PMID- 29003169 TI - Cancer in India. PMID- 29003168 TI - Note on the Prevalence of Elephantiasis, Filariasis and Hydrocele Amongst Prisoners in the Cuttack District Jail. PMID- 29003171 TI - A Case of Excision of the Os Calcis. PMID- 29003170 TI - A Case of Cut Throat. PMID- 29003172 TI - Service Notes. PMID- 29003173 TI - Extracts from Foreign Journals. PMID- 29003174 TI - Scarlet Fever at Rawal Pindi. PMID- 29003176 TI - The Bombay Medical and Physical Society. PMID- 29003175 TI - Note on the Mycoid Body Found in the Blood Corpuscles in Remittent Fevers. PMID- 29003178 TI - A Malaria Combine. PMID- 29003177 TI - Hernia of the Bladder. PMID- 29003179 TI - Vesical Calculus: Read before the Norfolk Branch of the British Medical Association. PMID- 29003180 TI - Note on the Climate of Erythrea. PMID- 29003181 TI - A Case of Insular or Disseminate Sclerosis. PMID- 29003182 TI - AEtiology of Leprosy. PMID- 29003183 TI - Moot Points in Bilharziosis. PMID- 29003184 TI - Case of Depressed Fracture of Skull with Removal of a Tablespoonful of Brain Matter and Recovery. PMID- 29003185 TI - Case of Detachment of Odontoid Process of Axis with Fracture of Atlas. PMID- 29003186 TI - Two Cases of Spina Bifida: Operation-Recovery. PMID- 29003188 TI - Bilharzia Disease in India. PMID- 29003187 TI - Some Septic Infections and Nervous Lesions Following Chancroids. PMID- 29003189 TI - Undulant Fever. PMID- 29003190 TI - Bengal Lunatic Asylums. PMID- 29003191 TI - Case of Cerebral Irritation. PMID- 29003192 TI - The Kasr-el-'Ain Hospital, Cairo. PMID- 29003193 TI - A Contribution to the Discussion on the AEtiology of Lepra. PMID- 29003195 TI - Paraffin Injection for Nasal Deformity. PMID- 29003194 TI - Current Topics. PMID- 29003197 TI - The War in South Africa. PMID- 29003196 TI - Government of Bengal Administration Report: 1901-1902. PMID- 29003198 TI - The Medical Service of the American Army. PMID- 29003199 TI - Report on Malaria for the Month of November 1899. PMID- 29003201 TI - An International Congress on Tuberculosis. PMID- 29003200 TI - The Destruction of Mosquitos. PMID- 29003202 TI - Internal Jugular Vein Accidentally Opened. PMID- 29003203 TI - Ectopic Gestation-A Series of Eight Cases Treated by Abdominal Section. PMID- 29003205 TI - The Annual Meeting of the British Medical Association. PMID- 29003204 TI - Notes on Some Surgical Cases. PMID- 29003206 TI - Service Notes. PMID- 29003207 TI - Tuberculosis in India. PMID- 29003209 TI - Why Not a Veterinary Faculty. PMID- 29003210 TI - A Case of Inflamed Strangulated Inguinal Hernia: Operation: Removal of 41/2 Inches of Omentum: Recovery. PMID- 29003212 TI - Organizations for Research. PMID- 29003211 TI - Enteric Fever in Natives of India. PMID- 29003213 TI - Current Topics. PMID- 29003214 TI - Malarial Pigmentation. PMID- 29003215 TI - The Destruction of Mosquitos. PMID- 29003217 TI - Surgical Cases. PMID- 29003216 TI - Two Cases of Compound Depressed Fracture of the Skull-Recovery. PMID- 29003218 TI - Sir Joseph Fayrer's Reminiscences. PMID- 29003219 TI - The Mosquito Theory. PMID- 29003220 TI - Body Temperatures of Gurkhas and Other Hill Tribes. PMID- 29003222 TI - Cases of Ectopic Gestation. PMID- 29003221 TI - Cancer of the Pleura. PMID- 29003223 TI - The Plague Epidemic in Russia in 1899. PMID- 29003225 TI - Enteric Fever in India. PMID- 29003224 TI - Parasites Found on Mosquitoes. PMID- 29003228 TI - The Suppression of Rabies in Great Britain. PMID- 29003227 TI - A Case of Depressed Fracture of the Skull. PMID- 29003229 TI - Anchylostomiasis. PMID- 29003230 TI - Upon a Type of Acute Lobar Pneumonia Encountered in the Tochi Valley Amongst Native Troops and Followers. PMID- 29003231 TI - Elephantiasis of the Penis. PMID- 29003234 TI - Current Topics. PMID- 29003233 TI - The Prophylactic Use of Quinine. PMID- 29003232 TI - Plague Commission Report. PMID- 29003235 TI - A Case of Hysterical Coma. PMID- 29003236 TI - Difficulties in the Performance of Lithotrity, etc. PMID- 29003237 TI - The Etiology and Pathology of Yaws. PMID- 29003239 TI - The Annual Meeting of the British Medical Association. PMID- 29003238 TI - Service Notes. PMID- 29003240 TI - Hints for the Inquiry into the Prevalence of the Anchylostoma in India. PMID- 29003242 TI - Epidemic Dysentery in Japan. PMID- 29003241 TI - Two Cases of Hepatic Abscess: With Clinical Remarks. PMID- 29003243 TI - Intracerebral Injection of Antivenine. PMID- 29003244 TI - A Case of Post-Hemiplegic Athetosis. PMID- 29003245 TI - The Teaching of Hygiene in Indian Universities. PMID- 29003246 TI - Current Topics. PMID- 29003247 TI - The Serum Treatment of Leprosy. PMID- 29003248 TI - The Report of the India Plague Commission. PMID- 29003249 TI - Enteric Fever in Natives of India. PMID- 29003250 TI - A Case of Snake-Bite. PMID- 29003251 TI - The Polyclinic. PMID- 29003252 TI - Poisoning by Castor-Oil Seeds. PMID- 29003254 TI - The Destruction of Mosquitos. PMID- 29003253 TI - "Baheda" Poisoning. PMID- 29003255 TI - Rational Dress for the Soldier. PMID- 29003257 TI - The War. PMID- 29003258 TI - Service Notes. PMID- 29003259 TI - The AEtiology of Goitre. PMID- 29003260 TI - Treatment of Guinea-Worm. PMID- 29003261 TI - Indigenous Drugs. PMID- 29003262 TI - Ten Years' Surgical Work in the Mission Hospital, Kashmir. PMID- 29003263 TI - Further Researches on Olutkombol in Dysmenorrhoea. PMID- 29003264 TI - Corrigendum. AB - [This corrects the article on p. 121 in vol. 35.]. PMID- 29003265 TI - On the Metamorphosis of the Filaria Nocturna in Mosquitos of the Anopheles Genus. PMID- 29003266 TI - Texas Cattle Fever and the Mosquito Malaria Theory. PMID- 29003267 TI - Service Notes. PMID- 29003268 TI - Sir William MacCormack. PMID- 29003269 TI - Beri-Beri in the 28th Regt., Madras Infantry. PMID- 29003270 TI - A Criticism of Col. Lawrie's Experiments. PMID- 29003271 TI - Sclerotising or Cicatrising Granuloma. PMID- 29003272 TI - Renal Calculus Treated by Nephrectomy. PMID- 29003274 TI - The Symptoms of Stone in the Kidney. PMID- 29003275 TI - The Famous Marches of the Guides. PMID- 29003273 TI - Case of Ectopic Gestation. Abdominal Section-Recovery. PMID- 29003276 TI - Emphysema of the Intestine Produced by Round Worm. PMID- 29003277 TI - Ectopic Gestation: A Series of Eight Cases Treated by Abdominal Section. PMID- 29003279 TI - The Unpopularity of the R. A. M. C. PMID- 29003278 TI - The Test for Haemoglobin. PMID- 29003280 TI - De Impotentia. PMID- 29003281 TI - Medical Societies. PMID- 29003282 TI - Wound Pensions. PMID- 29003284 TI - Case of Septic Endocarditis. PMID- 29003283 TI - Report on Cases of Malarial Fever at the Hyderabad Medical School, during the Month of October 1899. PMID- 29003285 TI - The Medical Arrangements. PMID- 29003286 TI - Dysentery versus Colitis. PMID- 29003288 TI - The War in South Africa. PMID- 29003287 TI - Current Topics. PMID- 29003289 TI - The Extermination of Malaria. PMID- 29003291 TI - Two Interesting Medico-Legal Cases: (A) False Charge of Dacoity with Self Inflicted Injuries; (B) Rape-Question of Age of the Girl. PMID- 29003292 TI - Regimental Marching. PMID- 29003293 TI - Report on Malarious Fever for the Month of December 1899. PMID- 29003294 TI - Current Topics. PMID- 29003295 TI - A Case of Snake-Bite Treated with Calmette's Antivenine. PMID- 29003296 TI - Recent Italian Work on Mosquito Malaria. PMID- 29003297 TI - Vaccination in England. PMID- 29003298 TI - Mosquitos and Malaria. PMID- 29003299 TI - A Case of Snake-Bite Treated by Antivenine-Recovery. PMID- 29003300 TI - When Does the 20th Century Commence. PMID- 29003301 TI - Snake Charmers and Their Ways. PMID- 29003303 TI - Kangri-Burn Epithelioma in Kashmir. PMID- 29003304 TI - Calmette's Serum. PMID- 29003305 TI - An Examination of 400 Slides of Night Blood for Filarial Embryos. PMID- 29003306 TI - A Note on Snakes, Snake-Bite and Their Treatment. PMID- 29003307 TI - Anchylostoma in Madras. PMID- 29003308 TI - Service Notes. PMID- 29003310 TI - The Crusade against Rats. PMID- 29003309 TI - On the Use of Cinchonidine Sulphate in Reducing the Prevalence of 'Fever' Cases in Jails. PMID- 29003311 TI - 1899. PMID- 29003312 TI - The Mauser Bullet. PMID- 29003314 TI - Prophylactic and Curative Inoculations. PMID- 29003313 TI - Cases of Ectopic Gestation. PMID- 29003315 TI - Malta and Enteric Fevers in the Delhi-Hissar Districts. PMID- 29003316 TI - The Perchloride Treatment in Plague. PMID- 29003317 TI - The Treatment of Night-Blindness. PMID- 29003319 TI - London Letter. PMID- 29003318 TI - The Treatment of Skin Diseases in Frankfurt: Notes from Dr. Karl Herxheimer's Clinic and Policlinic. PMID- 29003320 TI - A Case of Transposition of Viscera. PMID- 29003321 TI - The Annual Reports of the Lunatic Asylums of Bengal, Madras and the Punjab for 1899. PMID- 29003322 TI - Case of Caesarian Section. PMID- 29003324 TI - Current Topics. PMID- 29003323 TI - Service Notes. PMID- 29003325 TI - A Rhinoplastic Operation. PMID- 29003326 TI - The Widal Re-Action in the Diagnosis of Typhoid Fever: A Resume of What Is Known on the Subject. PMID- 29003327 TI - Acute Inflammation of the Gall-Bladder and Liver Abscess: Operation. PMID- 29003329 TI - The Dublin Asylum Form of Beri-Beri. PMID- 29003328 TI - Researches into the Intra-Corpuscular Parasites Found in the Blood of Lizards. PMID- 29003330 TI - Case of Ovariotomy. PMID- 29003331 TI - On the Cause of Boils and Carbuncles and Some Points in Their Treatment. PMID- 29003332 TI - The Biological Treatment of Sewage. PMID- 29003334 TI - Tuberculosis in India. PMID- 29003333 TI - Current Topics. PMID- 29003335 TI - Acetic Acid an Antidote to Carbolic Acid. PMID- 29003337 TI - Botanical Names of Pulses, &c. PMID- 29003336 TI - Some Abdominal Sections in Mofussil Practice. PMID- 29003338 TI - Enteric Fever in India and the Water-Supply. PMID- 29003339 TI - Chloroform. PMID- 29003341 TI - The Midwives Bill. PMID- 29003340 TI - Malaria and Petroleum. PMID- 29003342 TI - A New Sort of Unqualified Assistant. PMID- 29003343 TI - An Outbreak of Cerebro-Spinal Fever in the Raipur Central Jail in 1899-1900. PMID- 29003344 TI - Four Cases of Abdominal Operations at the Mooltan Hospital. PMID- 29003345 TI - The London Medical Graduates' College and Polyclinic. PMID- 29003346 TI - Note on the Prevalence of Goitre and Enlarged Spleen Amongst the Population of Mymensingh. PMID- 29003349 TI - Service Notes. PMID- 29003347 TI - An Appeal against the Banishment of Sags. PMID- 29003350 TI - Malariology. PMID- 29003352 TI - Venereal Disease in the British Army. PMID- 29003351 TI - Abdominal Surgery at Gaya Hospital. PMID- 29003353 TI - The Ptomaine Origin of Scurvy. PMID- 29003354 TI - Precis of Bone Operations in the Kashmir Mission Hospital with Clinical Notes. PMID- 29003355 TI - Pneumonia in the Tochi Valley: Predisposing and Exciting Causes of the Disease; Characteristics of the Type: Treatment. PMID- 29003356 TI - A Garbled Quotation. PMID- 29003357 TI - The Army Medical Department Report for 1898. PMID- 29003359 TI - The Homoeopathic Medical School. PMID- 29003358 TI - An Outbreak of Cerebro-Spinal Fever in the Raipur Central Jail in 1899-1900. PMID- 29003360 TI - Serum Treatment of Plague. PMID- 29003361 TI - Extraction of Cataract in the Capsule. PMID- 29003362 TI - The Victoria Cross. PMID- 29003363 TI - Enteric Fever in the British Army. PMID- 29003364 TI - The Return of Sir William MacCormack and Mr. F. Treves. PMID- 29003366 TI - Preventive Inoculation for Enteric Fever. PMID- 29003365 TI - The Value of "Sags" as Antiscorbutics in the Jail Dietary. PMID- 29003368 TI - Filarial Metamorphosis in the Anopheles. PMID- 29003367 TI - Current Topics. PMID- 29003369 TI - On Tapping Ovarian Cysts. PMID- 29003370 TI - Service Notes. PMID- 29003371 TI - The Assam and Central Provinces Asylum Reports. PMID- 29003373 TI - Lt.-Col. Spencer's Case of Continued Fever. PMID- 29003374 TI - The Plague Problem Restated with Some Expert Errors. PMID- 29003375 TI - Service Notes. PMID- 29003376 TI - Ten Years' Joint Surgery in the Kashmir Mission Hospital. PMID- 29003377 TI - Our Ankylostoma Inquiry. PMID- 29003378 TI - Ankylostomiasis in the Andamans. PMID- 29003379 TI - Ankylostomiasis as a Cause of Anaemia and "Spongy Gums". PMID- 29003380 TI - Current Topics. PMID- 29003381 TI - The Treatment of Skin Diseases in Frankfurt. (Notes from Dr. Karl Herxheimer's Clinic and Policlinic). PMID- 29003383 TI - An Indian Grievance. PMID- 29003382 TI - Report on Cholera Epidemic in the Town of Muzaffarpur during October and November, 1899. PMID- 29003384 TI - A Note on the Suppression of Cholera in a Famine Camp. PMID- 29003385 TI - A Case of Fatal Septic Gangrene: Primary and Secondary Amputation. PMID- 29003386 TI - Medical Politics. PMID- 29003387 TI - The Tropical Diseases Section. PMID- 29003388 TI - Note on the Prevalence of Ascaris Lumbricoides in the Darbhanga District. PMID- 29003389 TI - The Ipswich Meeting. PMID- 29003390 TI - Renal Surgery in Kashmir. PMID- 29003392 TI - Ankylostoma Duodenale. PMID- 29003391 TI - An Operation for Piles. PMID- 29003393 TI - Two Cases of "Stone in the Ureter". PMID- 29003394 TI - Size of Ovarian Tumours. PMID- 29003395 TI - The Liverpool Tropical School. PMID- 29003397 TI - The Increase of Tuberculosis in the Jails of India. PMID- 29003396 TI - The Occurrence of Mediterranean or Malta Fever in Bombay. PMID- 29003398 TI - Current Topics. PMID- 29003399 TI - Note on the Mal-Treatment of Malarial Fevers and Its Consequences. PMID- 29003400 TI - The Opening of the London School of Tropical Medicine. PMID- 29003401 TI - The Procedure Adopted in the Plague Research Laboratory, Bombay, for Stoppering the Plague Prophylactic Bottles. PMID- 29003402 TI - Ten Years' Surgical Work in the Kashmir Mission Hospital. PMID- 29003403 TI - Note on the Prevalence of the Ankylostomum in Calcutta: For the I. M. G. Collective Investigation. PMID- 29003404 TI - Some Notes and Queries on Mosquitoes. PMID- 29003405 TI - A Garbled Quotation. PMID- 29003406 TI - Haemoglobinuric Fever in Malaria. PMID- 29003407 TI - The Widal Re-Action in the Diagnosis of Typhoid Fever: A Resume of What Is Known on the Subject. PMID- 29003408 TI - Therapeutic Preparations. PMID- 29003410 TI - Service Notes. PMID- 29003409 TI - A Note on Mr. Milton's Paper on Stone. PMID- 29003411 TI - Captain Rogers' Recent Investigation on Malaria. PMID- 29003413 TI - Discussion on Operation for Stone. PMID- 29003412 TI - Mr. Milton's Paper on Stone. PMID- 29003414 TI - The Discussion on Stone. PMID- 29003415 TI - The Cause of Beri-Beri. PMID- 29003416 TI - The Malaria Experiments. PMID- 29003417 TI - A Note on Two Cases of Pernicious Malarial Fever. PMID- 29003418 TI - The Plague. PMID- 29003419 TI - The Huxley Lecture. PMID- 29003420 TI - A Reply to Major Ross's Criticism. PMID- 29003421 TI - Two Cases of Infantile Scurvy. PMID- 29003422 TI - New Edition of Dr. Manson's Book. PMID- 29003423 TI - The Rajputana Medico-Topographical Histories. PMID- 29003424 TI - The Director-General's Note on Jails. PMID- 29003425 TI - The Treatment of Cholera. PMID- 29003426 TI - Carcinoma of the Penis: Notes on Eight Cases of Entire Removal by Pearce Gould's Method. PMID- 29003427 TI - The Treatment of Stone in the Bladder. PMID- 29003428 TI - Pyorrhoea Alveolaris or Scurvy. PMID- 29003429 TI - Surgeon-Major W. Poulett Harris's Book on Lithotomy. PMID- 29003430 TI - Some Old Indian Statistics and Notes on Operations for Stone. PMID- 29003431 TI - Ten Years of Litholapaxy. PMID- 29003432 TI - Keith's Perineal Litholapaxy at Hyderabad (Sindh). PMID- 29003433 TI - Litholapaxy in Children. PMID- 29003434 TI - Dr. Joseph Fayrer on Stone Operations in 1865. PMID- 29003435 TI - Stone in the Bladder-Operations for. PMID- 29003437 TI - Litholapaxy at Hyderabad (Sindh). PMID- 29003436 TI - The Treatment of Stone by Lithotomy and Litho Lapaxy. PMID- 29003439 TI - Our Special Number. PMID- 29003438 TI - The Comparative Safety of Litholapaxy and Lateral Lithotomy in Boys. PMID- 29003440 TI - Record Sized Stones. PMID- 29003441 TI - The Best Methods of Removing Large Calculi. PMID- 29003442 TI - Forbes-Keith's Methods at Hyderabad (Sindh): Perineal Lithotrity. PMID- 29003443 TI - Hints to Beginners. PMID- 29003444 TI - Lithotomy in Saharanpur in 1868. PMID- 29003445 TI - Litholapaxy at Gaya Pilgrim Hospital. PMID- 29003446 TI - A Plea for the More Extensive Use of Urethral Litholapaxy, Perineal Litholapaxy and Perineal Lithotrity, Based on an Analysis of 7,954 Cases. PMID- 29003447 TI - Some Cases of Stone Operated on by a Civil Hospital Assistant. PMID- 29003448 TI - Perineal Litholapaxy. PMID- 29003449 TI - Lithotomy versus Lithotrity in 1867. PMID- 29003450 TI - Note on Litholapaxy in Boys. PMID- 29003451 TI - Litholapaxy and Allied Operations. PMID- 29003453 TI - Litholapaxy in Females. PMID- 29003452 TI - Further Experiences in Litholapaxy. PMID- 29003454 TI - Stone Operations in Mooltan. PMID- 29003456 TI - The Revival of Suprapubic Lithotomy in England. PMID- 29003455 TI - The Operative Treatment of Vesical Calculus in Kashmir Based on 116 Consecutive Cases. PMID- 29003458 TI - A Few Aphorisms for Litholapaxy. PMID- 29003457 TI - The Giant Lithotrite. PMID- 29003460 TI - The Dawn of Litholapaxy. PMID- 29003459 TI - Historical Sketch of Stone in India. PMID- 29003462 TI - London Letter. PMID- 29003461 TI - Replies to Circular. PMID- 29003463 TI - Some Reasons Why Lithotomy Is Still Performed. PMID- 29003464 TI - Water-Itch. PMID- 29003466 TI - The Acclimatisation of Europeans in the Tropics. PMID- 29003465 TI - Notes on Some Uncommon Skin Diseases. PMID- 29003467 TI - Prevalence of Certain Intestinal Parasites in India; with Some Remarks on Kala Azar. PMID- 29003468 TI - Movable Kidney with Calculus and New Growth. PMID- 29003470 TI - The Saline Treatment of Dysentery: 102 Consecutive Cases. PMID- 29003469 TI - Intralaryngeal Papilloma. PMID- 29003472 TI - The Tata Gift. PMID- 29003471 TI - London Letter: Virchow's Oration-Haemoglobinuria and Quinine-The New Vaccination Act. PMID- 29003473 TI - The New Bombay Plague Regulations. PMID- 29003474 TI - Teachers' Certificates. PMID- 29003475 TI - Vital Statistics and Sanitation. PMID- 29003476 TI - Currrent Topics. PMID- 29003477 TI - Haemoglobinuria in a Case of Malarial Fever. PMID- 29003478 TI - Dr. Powell's Paper on Intestinal Parasites in India. PMID- 29003479 TI - An Unusual Case of Myocarditis. PMID- 29003480 TI - A Case of Chronic Intussusception. PMID- 29003481 TI - Microscopic Work in India. PMID- 29003482 TI - Transactions of Medical Societies. PMID- 29003483 TI - Plague and Filth. PMID- 29003484 TI - Report on the Cultivation of Proteosoma, Labbe, in Grey Mosquitos. PMID- 29003486 TI - Notes from European Eye Clinics, (1) Switzerland. PMID- 29003485 TI - Military Medical Journals. PMID- 29003487 TI - A Case of Poisoning from Commercial Cyanide of Potash, Corrosive Action. PMID- 29003488 TI - Indian Cigars. PMID- 29003489 TI - The Plague Commission on Haffkine's Anti-Plague Inoculation. PMID- 29003490 TI - Prevalence of Stone Amongst the Rice-Eating Population of Lower Bengal. PMID- 29003491 TI - A Case of Filarial Disease of the Pelvic Lymphatics Vessels Simulating Double Inguinal Hernia. PMID- 29003492 TI - The Employment of Setons in the District of Backergunge. PMID- 29003493 TI - London Letter. PMID- 29003494 TI - A Case of Typhoid Fever in a Native Prisoner. PMID- 29003495 TI - Current Topics. PMID- 29003496 TI - Current Literature. PMID- 29003497 TI - Service Notes. PMID- 29003498 TI - Dilatation of the Pupil in Chlorodyne Poisoning. PMID- 29003499 TI - The Post-Mortem Appearances in Cases of Asphyxia Caused by Drowning. PMID- 29003501 TI - The I. M. S. Uniform. PMID- 29003500 TI - Return of Sudden Deaths Requiring Coroner's Inquests for Five Years (from 1896 to 1900) in the City of Calcutta, with Remarks. PMID- 29003502 TI - Analysis of the Post-Mortem Examinations in the Murshidabad District during the Past 5 Years. PMID- 29003503 TI - Bullet Wound of Large and Small Intestine-Commencing Peritonitis-Operation: Recovery. PMID- 29003504 TI - A "Hard Case." PMID- 29003505 TI - Influence of Colour and Materials upon Anopheles. PMID- 29003506 TI - Chronic Inflammations of Lymphatic Glands in Rangoon. PMID- 29003507 TI - Notes on an Outbreak of Surra with Observations on the Trypansoma. PMID- 29003508 TI - A Case of Compound Depressed Fracture of the Skull.-Recovery. PMID- 29003509 TI - The Use of Cocaine in Minor Surgery. PMID- 29003510 TI - Pre-Service Surgeons. PMID- 29003511 TI - Five Cases of Perineal Lithotrity. PMID- 29003513 TI - A Further Note on the Occurrence of Typhoid Fever in the Natives of India. PMID- 29003512 TI - The Thyroid Gland and Puerperal Convulsions. PMID- 29003514 TI - The Robert Harvey Memorial Fund. PMID- 29003515 TI - The Occurrence of Typhoid Fever among the Natives of India. PMID- 29003517 TI - Current Topics. PMID- 29003516 TI - The Sanitary Commissioner's Note on Jails. PMID- 29003518 TI - Current Literature. PMID- 29003519 TI - Weights of Human Viscera in Natives of Bengal. PMID- 29003520 TI - Preliminary Note on "Pani-Ghao" or "Water-Sores". PMID- 29003521 TI - London Letter. PMID- 29003522 TI - Service Notes. PMID- 29003523 TI - Statistics of the Medico-Legal Investigations in Moradabad, 1896-1901 Inclusive. PMID- 29003524 TI - Therapeutic Preparations. PMID- 29003525 TI - The Pellagrous Affections of the Skin in North Behar. PMID- 29003526 TI - Current Literature. PMID- 29003527 TI - The Causation and Prevention of Malarial Fevers. PMID- 29003528 TI - Large Hydrocele of the Tunica Vaginalis Testis, Occupying the Major Part of the Abdominal Cavity. PMID- 29003529 TI - The Recent Outbreak of Mahamari (Plague) in Garhwal. PMID- 29003530 TI - A Leg Splint. PMID- 29003531 TI - The List of Qualified Medical Practitioners. PMID- 29003533 TI - Service Notes. PMID- 29003532 TI - Notes on the Hypodermic Injection of Quinine in Malarial Fevers. PMID- 29003534 TI - Wanted a Good Hair Dye. PMID- 29003535 TI - Why This Greatness Thrust upon Us. PMID- 29003536 TI - A Recurrence of Epidemic Dropsy in Calcutta in 1901. PMID- 29003537 TI - The Treatment of Hydrophobia. PMID- 29003538 TI - Current Topics. PMID- 29003539 TI - Climatic Buboes. PMID- 29003540 TI - A Case of Antero-Posterior Bullet Wound of Knee-Joint without Osseous Injury. PMID- 29003541 TI - A Case of "True" Intestinal Sand. PMID- 29003542 TI - Modern Views on Dysentery. PMID- 29003543 TI - London Letter. PMID- 29003544 TI - Further Experiments in Connection with the Pathology of Beri-Beri. PMID- 29003546 TI - The Promotion of Specialist Medical Officers. PMID- 29003545 TI - The Non-Recognition of Enteric Fever among Natives. PMID- 29003548 TI - A Medico-Legal Case. PMID- 29003547 TI - Involuntary Iridectomy. PMID- 29003549 TI - Two Cases of Death from Suffocation. PMID- 29003551 TI - Hypnotism in Therapeutics. PMID- 29003550 TI - Current Literature. PMID- 29003553 TI - The Factors Determining Malarial Endemicity. PMID- 29003552 TI - A Case of Tetanus. PMID- 29003554 TI - London Letter. PMID- 29003555 TI - Suppuration in Connection with a Simple Fracture of the Femur. PMID- 29003557 TI - The Gigantic Anti-Plague Campaign in the Punjab. PMID- 29003556 TI - Service Notes. PMID- 29003559 TI - London Letter. PMID- 29003558 TI - Report on Cerebro-Spinal Meningitis in the Bhagalpur Central Jail, 1900-1901. PMID- 29003560 TI - Is "Malarial Cachexia" Purely Malarial? PMID- 29003561 TI - Current Topics. PMID- 29003562 TI - Case of Landry's Paralysis. PMID- 29003563 TI - Encysted Vesical Calculus after Gunshot Wound of the Bladder. PMID- 29003565 TI - Service Notes. PMID- 29003564 TI - A Note on Jail Tuberculosis. PMID- 29003566 TI - A New Operation for Enlarged Spleen. PMID- 29003567 TI - Note on the Pathology of Mycetoma, and on the Part Played by the Lymphatic Vessels in the Spread of the Disease. PMID- 29003568 TI - Therapeutic Preparations. PMID- 29003569 TI - A Medico-Legal Case. PMID- 29003570 TI - My Story of a Demon-The Carbonic Oxide Gas: My Punishment for Want of Foresight. PMID- 29003571 TI - Is Antivenine of Any Value in Cobra Poisoning? PMID- 29003573 TI - Current Topics. PMID- 29003572 TI - Experiences in a Chinese Hospital. PMID- 29003574 TI - Information to Procure a Copy of the Circular of a Judicial Commissioner, Required. PMID- 29003575 TI - The Inunction Treatment of Syphilis as Carried out at Aix-La-Chapelle. PMID- 29003576 TI - Epidemic Malta Fever in Assam-A Short Preliminary Notice of Certain Recent Discoveries Relating to the True Nature of Kala-Azar. PMID- 29003577 TI - Procidentia Recti-Excision and Sigmoidopexy. PMID- 29003578 TI - A Case of Aneurism of the Ascending Aorta. PMID- 29003579 TI - Interscapulo-Thoracic Amputation. PMID- 29003580 TI - Medical Society.-Madras Branch, B.M.A. PMID- 29003581 TI - Mosquitos and Malaria. PMID- 29003582 TI - Syphilitic Pleurisy. PMID- 29003583 TI - A Few Surgical Notes. PMID- 29003584 TI - Service Notes. PMID- 29003585 TI - Current Topics. PMID- 29003586 TI - Notes on the Prevalence of Filariasis in the Calcutta Police Force. PMID- 29003587 TI - An Unusual Form of Bubonic Plague. PMID- 29003588 TI - Involuntary Iridectomy. PMID- 29003589 TI - Observation of the Clotting Power of the Blood in Plague. PMID- 29003590 TI - Case of Opium Poisoning. PMID- 29003591 TI - The Robert Harvey Memorial Fund. PMID- 29003592 TI - Cocaine as an Intoxicant. PMID- 29003593 TI - Correspondence. PMID- 29003594 TI - Extensive Operation for Aneurism. PMID- 29003595 TI - A Preliminary Report of the Royal Society Malaria Commission. PMID- 29003596 TI - A Case of "Syphilitic Fever". PMID- 29003597 TI - Some Cases of Cerebro-Spinal Meningitis (Epidemic?). PMID- 29003599 TI - The Therapeutics of Semi-Carpus Anacardium: Dhobi's Nut. PMID- 29003598 TI - A Case of Enchondroma of Sub-Maxillary Gland. PMID- 29003601 TI - A Case of Snake-Bite. PMID- 29003602 TI - Quartan Fever in Calcutta and Dacca. PMID- 29003603 TI - Suprapubic Lithotomy. PMID- 29003604 TI - Some Practical Suggestions for the Prevention of Malarial Fevers. PMID- 29003605 TI - London Letter. PMID- 29003606 TI - American Views on Heatstroke. PMID- 29003608 TI - Service Notes. PMID- 29003607 TI - A Chronic Case of Malarial Fever. PMID- 29003610 TI - Medical Society: The Bombay Medical and Physical Society. PMID- 29003609 TI - Some Remarks on Captain Rost's Paper on Beri-Beri. PMID- 29003611 TI - Army Medical Organisation in the Field. PMID- 29003612 TI - Hydatid of the Liver. PMID- 29003613 TI - London Letter. PMID- 29003614 TI - The Least Quantity of Food a Man Can Live on. PMID- 29003615 TI - Elephantiasis of the Scrotum and Penis. PMID- 29003616 TI - Current Topics. PMID- 29003617 TI - Death from Snake-Bite. PMID- 29003618 TI - A Series of Cases of Heart Disease. PMID- 29003619 TI - A Case of Thrombosis of the Middle Cerebral Artery after Normal and Aseptic Labour. PMID- 29003621 TI - A Summary of Ehrlich's Theory of Immunity. PMID- 29003620 TI - Three Cases of Snake-Bite (Daboia Russellii). PMID- 29003622 TI - Malaria and Kala-Azar. PMID- 29003623 TI - A Case of Hysteria with Diuresis. PMID- 29003624 TI - Notes of a Case of Scarlet Fever in Ranchi, Chota Nagpur. PMID- 29003625 TI - A Case of Lithotomy. PMID- 29003626 TI - A Note on Dengue Fever. PMID- 29003627 TI - Note on Kala-Azar. PMID- 29003628 TI - Liver Abscess Causing Acute Jaundice by Pressure on the Hepatic Duct. PMID- 29003629 TI - Further Note on Intestinal Sand. PMID- 29003631 TI - A Method of Direct Cultivation. PMID- 29003630 TI - Some Cases of Sudden Death in Native Regiments. PMID- 29003632 TI - Six Cases of Melancholic Stupor. PMID- 29003633 TI - Medical Societies: Port Blair Medical Society. PMID- 29003635 TI - Current Topics. PMID- 29003634 TI - The Introduction of Vaccination into India. PMID- 29003636 TI - Note on Serum Reactions and the Temperature Curve in Chronic Malaria Including Kala-Azar. PMID- 29003637 TI - The Use of Betelnut as a Cause of Cancer in Malabar. PMID- 29003638 TI - A Case of Atony of the Bladder. PMID- 29003639 TI - Case of Cerebro-Spinal Fever Simulating Poisoning. PMID- 29003640 TI - Cases of Reversed Peristalsis. PMID- 29003641 TI - London Letter. PMID- 29003643 TI - Service Notes. PMID- 29003642 TI - Some Cases of Malignant Disease in Natives of India. PMID- 29003644 TI - Enteric Fever and Sewage Disposal in India. PMID- 29003645 TI - Note on the Analysis of the Biliary Concretions. PMID- 29003646 TI - The Term "Remittent" as Applied to Fevers. PMID- 29003647 TI - Some Notes on Cerebro-Spinal Fever. PMID- 29003648 TI - Notes on a Case of Subpleural Abscess, &c. PMID- 29003649 TI - Eyesight in the Army. PMID- 29003650 TI - Notes on the Radical Cure of Hydrocele and Haematocele. PMID- 29003651 TI - The Importance of the Role Played by Mosquitos in Tropical Pathology : With a Brief Description of the Differences between Anopheles and Culex and a Classification of the Indian Anopheles. PMID- 29003652 TI - Glasses in the Army. PMID- 29003653 TI - The New Therapeutics. PMID- 29003655 TI - London Letter. PMID- 29003654 TI - Service Notes. PMID- 29003656 TI - Ligature of Vas Deferens, &c. PMID- 29003657 TI - A Case of Gangrene, &c. PMID- 29003658 TI - The Treatment of Typhoid Fever by the Woodbridge Method in India. PMID- 29003659 TI - An Interesting Case of Acute Pneumonia. PMID- 29003661 TI - Abdominal Wound, &c. PMID- 29003660 TI - Cercomonads in Ulcers. PMID- 29003662 TI - Amputation of the Upper Extremity &c. PMID- 29003663 TI - A Peculiar Case of Malignant Tertian Fever. PMID- 29003664 TI - Current Topics. PMID- 29003666 TI - Therapeutic Notes, &c. PMID- 29003665 TI - Stool Inspection Chamber. PMID- 29003667 TI - Influence of Colour upon Anopheles. PMID- 29003669 TI - The Late Surgeon-General Robert Harvey, I.M.S. PMID- 29003668 TI - The Iodine Terchloride Treatment of Plague. PMID- 29003670 TI - London Letter. PMID- 29003671 TI - Gastrotomy for Removal of Foreign Bodies (55 Rupees) from the Stomach-Recovery. PMID- 29003673 TI - Service Notes. PMID- 29003672 TI - Current Topics. PMID- 29003675 TI - Current Literature. PMID- 29003674 TI - Anopheles Mosquitos in Tezpur, Assam. PMID- 29003676 TI - Typhoid as a Common Continued Fever of Natives in Calcutta. PMID- 29003678 TI - Pre-Service Surgeons. PMID- 29003679 TI - The War against Mosquitos. PMID- 29003677 TI - A Preliminary Report of the Observations of the Habits of Anopheles. PMID- 29003682 TI - Annus Medicus. PMID- 29003680 TI - Cases of Gynaecomastia. PMID- 29003683 TI - Mosquitos and Malaria: Some Objections to the Theory. PMID- 29003684 TI - Cancer in India. PMID- 29003685 TI - Current Literature. PMID- 29003687 TI - A Case of Penetrating Wound of the Abdomen with Protrusion of the Intestine: Recovery. PMID- 29003686 TI - Case of Hydatidiform Mole-Natural Expulsion: Recovery. PMID- 29003688 TI - A Decade of Tumour Surgery in the Kashmir Mission Hospital. PMID- 29003689 TI - Leprosy and Ainhum. PMID- 29003690 TI - The Best Operation for Radical Cure of Inguinal Hernia. PMID- 29003691 TI - Service Notes. PMID- 29003692 TI - Surgeon William Pitts Muston. PMID- 29003693 TI - The Effect of a Fever Attack on Tropical Liver. PMID- 29003695 TI - Horny Growth Arising from Neglected Sebaceous Cyst. PMID- 29003694 TI - Report on an Experimental Enquiry on the Disinfection of Floors for Plague. PMID- 29003696 TI - A Case of Snake-Bite. PMID- 29003697 TI - The Anatomy of the Mosquito. PMID- 29003698 TI - Case of Hydrophobia Treated with Leaves of Acacia Arabica (Babul): Recovery. PMID- 29003700 TI - Irrigation, Mosquitos, and Malaria. PMID- 29003699 TI - Involuntary Iridectomy. PMID- 29003701 TI - London Letter. PMID- 29003702 TI - Some Important Indigenous Drugs and Their Uses. PMID- 29003703 TI - Case of Penetrating Abdominal Wound: Recovery. PMID- 29003704 TI - A Curious Case of Urinary Fistulae. PMID- 29003705 TI - Involuntary Iridectomy. PMID- 29003707 TI - Current Topics. PMID- 29003708 TI - The Indiscriminate Use of the Lathi. PMID- 29003709 TI - Injuries Caused by Lathi Blows. PMID- 29003710 TI - Notes on Rupture of the Spleen. PMID- 29003711 TI - Service Notes. PMID- 29003712 TI - Adipocere in India. PMID- 29003713 TI - Medico-Legal Notes from Alipore. PMID- 29003714 TI - Medico-Legal Notes. PMID- 29003715 TI - Some Cadaveric Phenomena. PMID- 29003716 TI - Decomposition. PMID- 29003717 TI - The Frequency of Poisoning in Calcutta, with Some Illustrative Cases. PMID- 29003718 TI - Medical Evidence in India. PMID- 29003719 TI - Our Special Medico-Legal Number. PMID- 29003720 TI - Six Cases of Ruptured Spleen, Including a Case of Spontaneous Rupture of an Enlarged Spleen. PMID- 29003721 TI - Notes of Medico-Legal Cases. PMID- 29003722 TI - The Differentiation of Crude Excise Opium. PMID- 29003724 TI - Methods of Criminal Abortion in India. PMID- 29003723 TI - Perforation of the Stomach and Duodenum from Disease. A Cause of Suspicious Death. PMID- 29003725 TI - Tables of Weights of Viscera. PMID- 29003726 TI - Notes of Some Toxicological Experiences in Bengal and in the Punjab. PMID- 29003727 TI - Crime in Insanity. PMID- 29003729 TI - Miner's Pthisis. PMID- 29003728 TI - Medical Examination in Cases of Rape. PMID- 29003731 TI - Jail Stomatitis. PMID- 29003730 TI - The Effect of Creosote Rubbing upon High Temperature in Remittent Fever. PMID- 29003732 TI - Piroplasmosis: A History of the Discovery of the Donovan Bodies in Madras. PMID- 29003733 TI - Widows' Pensions. PMID- 29003734 TI - Vision of Native Soldiers. PMID- 29003735 TI - An Outbreak of Plague at Arrah in 1902-1903. PMID- 29003736 TI - Differentiation of Human Blood. PMID- 29003737 TI - Service Notes. PMID- 29003738 TI - Case of Large Naevus-Excision : Recovery. PMID- 29003739 TI - Patent Foods. PMID- 29003740 TI - Editorial Notes on Current Topics. PMID- 29003741 TI - Therapeutic Notes and Preparations. PMID- 29003742 TI - Medicine. PMID- 29003743 TI - A Method of Preventing Death from Snake-Bite, Capable of Common and Easy Practical Application. PMID- 29003745 TI - The Indian Medical Service. PMID- 29003744 TI - Observations on the Effect of the Injection of Leprolin. PMID- 29003746 TI - Human and Bovine Tuberculosis. PMID- 29003747 TI - An Overlooked Sponge. PMID- 29003748 TI - Obstetrics and Midwifery. PMID- 29003750 TI - Chloroformed Vaccine Lymph. PMID- 29003749 TI - A Unique Case of Intestinal Obstruction. PMID- 29003752 TI - Medicine. PMID- 29003751 TI - A Case of Myxoedema. PMID- 29003753 TI - Diphtheria in Hyderabad. PMID- 29003755 TI - Service Examinations. PMID- 29003754 TI - The "Malarial Cachexia of India". PMID- 29003756 TI - Sanitary Inspectors in Madras. PMID- 29003757 TI - Excision of Tuberculous Glands. PMID- 29003758 TI - Foreign Journals, Extracts from. PMID- 29003760 TI - Sea-Sickness. PMID- 29003759 TI - Insanity Following the Use of Indian Hemp. PMID- 29003762 TI - Family Pensions. PMID- 29003761 TI - Dermoid Cysts. PMID- 29003764 TI - Editorial Notes on Current Topics. PMID- 29003763 TI - Medical Education. PMID- 29003765 TI - Case of Abdominal Pregnancy : Operation : Recovery: Comments on the Case. PMID- 29003767 TI - Widows' Pensions. PMID- 29003766 TI - Surgery of Cancer of Penis. PMID- 29003768 TI - Diplomas in Tropical Medicine. PMID- 29003769 TI - Indian Hemp Drugs and Insanity. PMID- 29003771 TI - Service Notes. PMID- 29003770 TI - Casualties in Tibet. PMID- 29003772 TI - Robert Koch. PMID- 29003773 TI - The Romownosky Stain. PMID- 29003774 TI - Indian Friends and Acquaintances. PMID- 29003776 TI - Editorial Notes on Current Topics. PMID- 29003775 TI - Crypt-Opthalmia Case. PMID- 29003777 TI - Hysterical Catalepsy. PMID- 29003778 TI - A Case of Hermaphrodite. PMID- 29003780 TI - The Report on Lathyrism. PMID- 29003779 TI - Jameson. PMID- 29003781 TI - Bovril, the Doctor's Ally. PMID- 29003782 TI - Medicine. PMID- 29003783 TI - Case of Impacted Stone. PMID- 29003785 TI - Service Notes. PMID- 29003784 TI - Further Notes on the Cultivation of the Bacillus Leprae and the Treatment of Leprosy by the Injections of a Leprolin. PMID- 29003786 TI - Adrenalin in Plague. PMID- 29003788 TI - Operation for Liver Abscess. PMID- 29003787 TI - Commonsense Policy of Plague. PMID- 29003789 TI - Obstetrics and Gynaecology. PMID- 29003790 TI - Plague in Ferozepore: 1904 (With Some Deductions as to the Nature of Plague). PMID- 29003791 TI - Case of Ovariotomy. PMID- 29003792 TI - Use of Guaiquin in Chronic Fevers. PMID- 29003793 TI - Trypanosomes in India. PMID- 29003794 TI - Anti-Malarial Sanitation in India. PMID- 29003795 TI - Elephantiasis of Penis. PMID- 29003796 TI - Finsen. PMID- 29003799 TI - Prof. Osler Goes to Oxford. PMID- 29003797 TI - Notes on a Case of General Lymphadenoma (Hodgkin's Disease). PMID- 29003800 TI - The Manuscripts of Naples and the Vatican, and That of Boncompagni (Albertotti) Concerning the Ophthalmic Work of Benvenuto, with Some Considerations and Theories of Reclination of Cataract. PMID- 29003798 TI - The Oxford Meeting, B.M.A. PMID- 29003801 TI - Treatment of Goitre with Iodine. PMID- 29003802 TI - The New Constitution. PMID- 29003803 TI - A Step Forward in Indian Sanitation. PMID- 29003804 TI - Ultra Violet Rays. PMID- 29003805 TI - Compulsory Notification of Enteric Fevers in India. PMID- 29003807 TI - Intracranial Operation for Cure of Trigeminal Neuralgia. PMID- 29003806 TI - Case of Gastric Disease with Tetany. PMID- 29003808 TI - Wire-Gauze Protection of Dwellings. PMID- 29003810 TI - Malta Fever Commission. PMID- 29003809 TI - Surgery. PMID- 29003811 TI - Notes on Some Cases of Frost Bite. PMID- 29003812 TI - Anti-Malarial Sanitation in India. PMID- 29003813 TI - Permanganate in Snake Poison. PMID- 29003814 TI - The Use of Izal in the Treatment of Tropical Dysentery. PMID- 29003815 TI - Another Case of Spontaneous Rupture of the Spleen. PMID- 29003816 TI - Why Has Calcutta No Branch of B. M. A. PMID- 29003817 TI - Preventive Medicine as a Factor in Empire Building. PMID- 29003818 TI - Service Notes. PMID- 29003819 TI - Entertainments and Excursions. PMID- 29003820 TI - The Sections. PMID- 29003821 TI - Editorial Notes on Current Topics. PMID- 29003822 TI - Wound of Thorax and Hernia of Lung. PMID- 29003823 TI - Cholera in Persia. PMID- 29003824 TI - The Cancer Research Fund. PMID- 29003825 TI - Permanganate in Opium Poisoning. PMID- 29003826 TI - The Late Dr. Mohendra Lal Sircar, C.L.E. PMID- 29003827 TI - Notes on the Destruction of Mosquitoes in Bijapur. PMID- 29003828 TI - Lemna Minor as a Preventive against Mosquitoes. PMID- 29003829 TI - An Outbreak of True Beri-Beri in an Assam Jail. PMID- 29003831 TI - Medical Defence. PMID- 29003830 TI - Dr. Durham's Report on Beri-Beri. PMID- 29003833 TI - The British Medical Association. PMID- 29003832 TI - Piroplasma or Pyroplasma. PMID- 29003834 TI - Pathology, &c. PMID- 29003835 TI - Notes on the Cultivation of Streptothrix Madurae. PMID- 29003836 TI - A Series of Five Cases of Hydrocephalus. PMID- 29003837 TI - The Late Deputy Surgeon-General H. Cayley, C.M.G. PMID- 29003838 TI - Editorial Notes on Current Topics. PMID- 29003839 TI - A Question of Priority. PMID- 29003842 TI - Service Notes. PMID- 29003840 TI - A Case of Spontaneous Rupture of the Spleen. PMID- 29003843 TI - Diagnosis of Malta Fever. PMID- 29003844 TI - A Pay Grievance. PMID- 29003845 TI - Further Notes on the Cultivation of the Bacillus Leprae and the Treatment of Leprosy by the Injections of a Leprolin. PMID- 29003846 TI - Obstetrics and Gynaecology. PMID- 29003847 TI - Consultation of Medical Witnesses. PMID- 29003849 TI - The Medical Amendment Act. PMID- 29003848 TI - Report on Plague and Inoculation Operations, Amritsar District. PMID- 29003851 TI - An X-Ray Case. PMID- 29003850 TI - Plague: A Soil Infection. PMID- 29003852 TI - Leprosy in the Garo Hills, Assam. PMID- 29003853 TI - Service Notes. PMID- 29003854 TI - Piroplasma Bigeminum. PMID- 29003855 TI - How to Cure Enteric Fever. PMID- 29003857 TI - The Prevention of Tuberculosis. PMID- 29003858 TI - Notes of Cases of Paralysis Treated by "Massage" in the Campbell Hospital. PMID- 29003859 TI - Editorial Notes on Current Topics. PMID- 29003860 TI - Scurvy in Somaliland. Notes on the Condition of the Blood Serum. PMID- 29003862 TI - The Antimalarial Operations at Mian Mir. PMID- 29003861 TI - Frost-Bite in the Tibet Mission Force. PMID- 29003864 TI - Intravenous Injections of Iodoform in Phthisis. PMID- 29003863 TI - Missing Forceps. PMID- 29003865 TI - A Rare Congenital Deformity of the Eyes. PMID- 29003866 TI - Case of Distoma Crassum or Buski. PMID- 29003867 TI - The Late Sir Henry Thompson, F.R.C.S. PMID- 29003868 TI - X-Rays in Court. PMID- 29003869 TI - Ankylostoma Infection. PMID- 29003870 TI - The Bengal Branch of Dufferin Fund. PMID- 29003871 TI - Obstetrics and Gynaecology. PMID- 29003872 TI - Service Notes. PMID- 29003873 TI - Medicine. PMID- 29003874 TI - Intestinal Animal Parasites in Behar and Orissa. PMID- 29003876 TI - Some Notes on Ankylostomiasis in Assam. PMID- 29003877 TI - Six Cases of Tetanus. PMID- 29003875 TI - The Piroplasmata in Man. PMID- 29003879 TI - An Universal Language of Science. PMID- 29003878 TI - Leishman-Donovan Bodies in Kala-Azar. PMID- 29003880 TI - Special Senses. PMID- 29003881 TI - A Case of Acute Haemorrhagic Pancreatitis. PMID- 29003883 TI - Spotted Fever of the Rocky Mountains. PMID- 29003882 TI - Two Cases of Enteritis Caused by Ascaris Lumbricoides. PMID- 29003884 TI - The Piroplasmata in Man. PMID- 29003886 TI - Editorial Notes on Current Topics. PMID- 29003885 TI - Brief Notes on Surgical Cases in the Medical College Hospital, Calcutta. PMID- 29003888 TI - Cobra Bite: Recovery. PMID- 29003887 TI - The R. A. M. C. College. PMID- 29003889 TI - Sulphonal Idiosyncrasy. PMID- 29003890 TI - Indian Medical Reports. PMID- 29003891 TI - Intestinal Parasites as Factors in the Mortality of Prisoners in Cannanore and Rajahmundry Jails. PMID- 29003893 TI - Diplomas in Tropical Medicine. PMID- 29003892 TI - A Note on the Occurrence of Intestinal Parasites in Ranchi, Chota Nagpur. PMID- 29003894 TI - Dental Surgeons for British Troops. PMID- 29003895 TI - Jail Stomatitis. PMID- 29003896 TI - Medicine. PMID- 29003897 TI - Anti-Typhoid Inoculation. PMID- 29003898 TI - How to Cure Enteric Fever. PMID- 29003899 TI - Editorial Notes on Current Topics. PMID- 29003900 TI - Circumcision and Midwives. PMID- 29003901 TI - Service Notes. PMID- 29003902 TI - Splenic Cachexia. PMID- 29003903 TI - A Preliminary Note on a Pyroplasmosis Found in Man, and in Some of the Lower Animals. PMID- 29003905 TI - Continental Eye Clinics. PMID- 29003906 TI - An English Hospital Report. PMID- 29003907 TI - Poisoning by Atropine. PMID- 29003908 TI - The Cultivation of the Bacillus Leprae. PMID- 29003909 TI - Notes on a Few Selected Operation Cases at the Petit Hospital, Bombay. PMID- 29003910 TI - A Contribution to the Study of the Action of Indian Cobra Poison. PMID- 29003911 TI - Cases from the Medical Wards of the Medical College Hospital, Calcutta. PMID- 29003912 TI - A Question of Priority. PMID- 29003913 TI - Medicine. PMID- 29003914 TI - Trypanosomiasis. PMID- 29003915 TI - Foreign Journals, Extracts from. PMID- 29003916 TI - A Case of Accessory Lobule of the Spigelian Lobe of the Liver. PMID- 29003917 TI - Service Notes. PMID- 29003918 TI - Enlarged Prostate. PMID- 29003919 TI - The Dum-Dum Spleen. PMID- 29003920 TI - The Bagdad Boil. PMID- 29003921 TI - Current Topics. PMID- 29003922 TI - A Case of Paralysis Agitans: "Parkinson's Palsy" with a Note on Its Causation. PMID- 29003924 TI - What Is Kala-Azar? PMID- 29003923 TI - Extract from Medical Journals: Diseases of Women and Children. PMID- 29003925 TI - The Cancer Enigma. PMID- 29003926 TI - Estimating the Specific Gravity of Urine. PMID- 29003928 TI - Plague at Sydney. PMID- 29003927 TI - Symblepharon and Its Treatment: Two Cases Treated Successfully by Transplantation of Flaps of Mucous Membrane from the Mouth. PMID- 29003929 TI - The Cholera Epidemic in Puri Town and District in July, 1902: And Its Spread Throughout Lower Bengal. PMID- 29003931 TI - The Pasteur Institute of India. PMID- 29003930 TI - Notes on a Case of Puerperal Eclampsia Treated by Morphia. PMID- 29003932 TI - A Note on Stiffness of the Arm after Amputation of the Breast: And a Good Way of Avoiding It. PMID- 29003933 TI - The Blood Examination of Three Thousand Four Hundred Cases of Febrile Disease in Bombay: Seasonal Prevalence of the Different Malaria Parasites. The Diagnosis of the Variety of the Young Stained Parasites. PMID- 29003934 TI - Trypanosomiasis. PMID- 29003936 TI - Arsenical Neuritis. PMID- 29003935 TI - A Needle Passing through the Intestinal Tract. PMID- 29003937 TI - Notes on a Case of Prolapsus Uteri with Pyosalpinx. PMID- 29003938 TI - A Fatal Case of Slow and Continuous Haemorrhage beneath the Dura Mater Producing Symptoms of Acute Ascending Paralysis: And Associated with Haemorrhage into the Stomach Immediately before Death. PMID- 29003939 TI - Case of Rupture of Intestine. PMID- 29003941 TI - The Services in 1903. PMID- 29003940 TI - A Case of Hyperpyrexia and Diabetes. PMID- 29003942 TI - Case of Large Goitre; Excision, Thyroidism: Recovery. PMID- 29003943 TI - A Short Note on the Parasite of Kala-Azar. PMID- 29003944 TI - Circumcision; Midwives and the Minor Operation. PMID- 29003946 TI - Extract from Medical Journals: Pathology and Bacteriology. PMID- 29003945 TI - Cerebro-Spinal Meningitis in Akyab Jail. PMID- 29003947 TI - Infant Mortality. PMID- 29003948 TI - Current Topics. PMID- 29003949 TI - Service Notes. PMID- 29003951 TI - London Letter. PMID- 29003950 TI - A Case of Karobi Poison. PMID- 29003952 TI - Delhi Boils. PMID- 29003954 TI - Case of Modified Talma's Operation for Hepatic Sclerosis with Ascites. PMID- 29003953 TI - Primary Carcinoma of the Pancreas, with Unusual Symptoms. PMID- 29003956 TI - Caesarian Section. PMID- 29003955 TI - Ankylostomiasis in the Punjab. PMID- 29003958 TI - Movable Kidney. PMID- 29003957 TI - Enlarged Prostate. PMID- 29003959 TI - Sulphonal Idiosyncrasy. PMID- 29003960 TI - Case of Pyonephrosis with Calculus: Kashmir Mission Hospital. PMID- 29003961 TI - The Blood Examination of Three Thousand Four Hundred Cases of Febrile Disease in Bombay. Seasonal Prevalence of the Different Malaria Parasites. The Diagnosis of the Variety of the Young Stained Parasites. PMID- 29003962 TI - A Case of Double Ablepharon (Congenital). PMID- 29003963 TI - Caesarian Sections. PMID- 29003964 TI - A Case of Severe Form of Malarial Anaemia Treated with Adrenalin. PMID- 29003965 TI - Carbolic Acid Treatment of Plague. PMID- 29003967 TI - Sulphonal Idiosyncrasy. PMID- 29003968 TI - Case of Lightning Stroke. PMID- 29003969 TI - Pay of Officiating Civil Surgeons. PMID- 29003970 TI - Note on a Case of Malignant Dermoid Cyst of the Neck: With Pathological Report and Pathological Comment. PMID- 29003971 TI - Wound of the Diaphragm by a Wild Boar. PMID- 29003972 TI - A Case of Syphilitic Disease of the Liver. PMID- 29003973 TI - Radical Cure of Stricture of the Urethra. PMID- 29003974 TI - Jail Stomatitis. PMID- 29003976 TI - Foreign Journals, Extracts from. PMID- 29003975 TI - Dr. Martin Jansson's Siderophone. PMID- 29003977 TI - The Recrudescence Theory of Plague. PMID- 29003978 TI - Extra-Uterine (Tubo-Abdominal) Gestation: The Fallopian Tube Showing an Accessory Ostium and a Diverticulum. PMID- 29003979 TI - Multiple Wounds of the Head. PMID- 29003981 TI - A Disclaimer. PMID- 29003980 TI - Bacteriology of Parangi (Yaws). PMID- 29003982 TI - Ligature of the Brachial Artery at the Bend of the Elbow. PMID- 29003983 TI - A Case of Sub-Phrenic Abscess. PMID- 29003984 TI - Plague: A Soil Disease. PMID- 29003985 TI - Editorial Notes on Current Topics. PMID- 29003986 TI - Insanity in Bengal. PMID- 29003988 TI - The Case of Miss Hickman. PMID- 29003987 TI - Service Notes. PMID- 29003989 TI - Lustig's Serum. PMID- 29003990 TI - Resisting Powers of the Larvae of Culicidae to Desiccation. PMID- 29003991 TI - A Forgotten Theory of Plague. PMID- 29003992 TI - Bayliss versus Coleridge. PMID- 29003994 TI - Current Topics. PMID- 29003993 TI - Malaria: As Seen in the Andamans Penal Settlement. PMID- 29003995 TI - Case of Pulmonary Osteoarthropathy. PMID- 29003996 TI - Circumcision : Midwives and 'The Minor Operation'. PMID- 29003997 TI - The Microbe of Yellow Fever. PMID- 29003999 TI - Special Senses. PMID- 29003998 TI - Diphtheria in the Madras Presidency. PMID- 29004000 TI - Extracts from Medical Journals-Medicine. PMID- 29004001 TI - Diseases of Women. PMID- 29004002 TI - Brief Notes on Surgical Cases in the Medical College Hospital, Calcutta. PMID- 29004003 TI - Report on a Small Outbreak of Cholera in 10th D. C. O. Lancers (Hodson's Horse) in June 1903. PMID- 29004004 TI - The Puff Direct. PMID- 29004005 TI - Service Notes. PMID- 29004006 TI - Poisonous Snakes and Calmette's Serum : A Successful Case. PMID- 29004007 TI - Supposed Dhatura Poisoning : A Personal Experience. PMID- 29004009 TI - Foreign Journals. PMID- 29004010 TI - Case of Depressed Fracture of the Skull: Operation, Recovery. PMID- 29004008 TI - Night-Mares and Some of Our Dreams. PMID- 29004011 TI - "Liver Chill" as a Factor of Disease in the Tropics. PMID- 29004012 TI - Doctors as Civil and Political Officers. PMID- 29004013 TI - Antivivisection Antics. PMID- 29004014 TI - A Simple Way to Compress the Subclavian Artery. PMID- 29004015 TI - Operation of Caesarian Section: Recovery. PMID- 29004016 TI - Involuntary Iridectomy. PMID- 29004017 TI - A Complication of Litholapaxy. PMID- 29004018 TI - Involuntary Iridectomy. PMID- 29004019 TI - The Reconstitution of the R. A. M. C. PMID- 29004021 TI - Medical Societies. PMID- 29004020 TI - Poisoning by Thevetia Nerifolia. PMID- 29004022 TI - On the Chemistry and Toxicology of Nerium Odorum, with a Description of a Newly Separated Active Principle. PMID- 29004023 TI - The Mortality of Operation for the Radical Cure of Hernia. PMID- 29004024 TI - Surgical Cases from Berhampur. PMID- 29004026 TI - Anopheles and Malaria in Calcutta. PMID- 29004025 TI - Case of Cobrabite and Antivenene. PMID- 29004028 TI - The New Therapeutics. PMID- 29004027 TI - Suggestions to Medical Officers of Field Hospitals. PMID- 29004030 TI - London Letters. PMID- 29004029 TI - Case of Snake-Bite. PMID- 29004032 TI - Guinea Grass as a Remedy for Herpes. PMID- 29004031 TI - Sterilization of Hands. PMID- 29004033 TI - Chronic Venereal Sore. PMID- 29004034 TI - Is the Goat Immune to Tuberculosis? PMID- 29004035 TI - The Mortality of Elephantiasis Operations. PMID- 29004036 TI - Current Topics. PMID- 29004037 TI - Surgical Cases. PMID- 29004038 TI - Rupture of Ovarian Cyst. PMID- 29004040 TI - Service Notes. PMID- 29004039 TI - Case of Rupture of Intestine. PMID- 29004041 TI - Typhoid Fever in Natives of Madras. PMID- 29004042 TI - Sags in Jail Diet. PMID- 29004043 TI - The Use of Ophthalmic Material in India. PMID- 29004045 TI - Celli's New Book on Malaria. PMID- 29004044 TI - The Surgical Treatment of Elephantiasis. PMID- 29004047 TI - London Letters. PMID- 29004046 TI - Service Notes. PMID- 29004048 TI - Corrections in Letter on Plague. PMID- 29004050 TI - The Serums of Viper and Cobra. PMID- 29004049 TI - The Forthcoming Special Ophthalmic Number. PMID- 29004051 TI - Hydrocele in India. PMID- 29004052 TI - Beri-Beri in Perak. PMID- 29004053 TI - Current Topics. PMID- 29004055 TI - The Malarial Fever Outbreak in the Punjab. PMID- 29004054 TI - Permanganate in Well Disinfection. PMID- 29004056 TI - Malta Fever in the Swat Valley. PMID- 29004057 TI - Mosquitoes and Malaria in Nagpur. PMID- 29004058 TI - Atresia of the Anterior Nares. PMID- 29004059 TI - Body Temperature of the Goorkha : Considered in Connection with a Predisposition to Pulmonary Phthisis. PMID- 29004060 TI - Notes on Eight Cases of Ovaro-Hysterectomy (Porro's Operation) Performed in the Ishwari Memorial Hospital, Benares, during the Last Five Years. PMID- 29004061 TI - Capt. Rogers' Investigations in Malaria. PMID- 29004063 TI - Service Notes. PMID- 29004062 TI - The Romanowsky Stain for Malarial Parasite. PMID- 29004064 TI - Corrigendum. AB - [This corrects the article on p. 24 in vol. 36.]. PMID- 29004065 TI - Ovariotomy in Burma. PMID- 29004066 TI - Bullet Wound of the Foot. Localisation by Means of the X-Ray-Extraction: Recovery. PMID- 29004068 TI - The Annual Report of Sanitary Commissioner, India. PMID- 29004069 TI - The Indian Addendum to the B. P. PMID- 29004071 TI - Treatment of Pneumonia. PMID- 29004070 TI - Notes on History of Bengal Medical Service. PMID- 29004072 TI - The Incubation Period of Cerebro-Spinal Fever. PMID- 29004074 TI - London Letters. PMID- 29004073 TI - Current Topics. PMID- 29004075 TI - A Veldt Sore: A Case for Diagnosis. PMID- 29004076 TI - Rhinoplasty. PMID- 29004077 TI - Surgical Cases. PMID- 29004078 TI - Larvicidal Reagents. PMID- 29004079 TI - Yellow Atrophy of Liver. PMID- 29004080 TI - Case of Splenectomy. PMID- 29004081 TI - Case of Enteric in Native Prisoner. PMID- 29004082 TI - Splenic Haemorrhage. PMID- 29004083 TI - Eyesight of Indian School-Boys. PMID- 29004084 TI - Service Notes. PMID- 29004085 TI - Effects of Cobra Venom, &c., on Blood. PMID- 29004087 TI - Cases of Enteric in Native Sepoys. PMID- 29004086 TI - Current Topics. PMID- 29004088 TI - The Medical Department, U. S. Army. PMID- 29004089 TI - Cerebro-Spinal Fever. PMID- 29004090 TI - Abscess of Liver. PMID- 29004091 TI - London Letters. PMID- 29004092 TI - Oriental Sore. PMID- 29004093 TI - Mosquito Brigades for India. PMID- 29004095 TI - A Year's Experience of Anopheles in Ellichpur. PMID- 29004096 TI - Ruptured Spleen. PMID- 29004097 TI - Case of Intestinal Obstruction. PMID- 29004098 TI - Service Notes. PMID- 29004099 TI - The Recent Calcutta Ghi-Adulteration Case. PMID- 29004100 TI - Chemistry of Nerium Odorum: The Coates' Memorial Prize Essay. PMID- 29004101 TI - Therapeutic Preparations. PMID- 29004102 TI - The Surgical Treatment of Chyluria. PMID- 29004103 TI - The Free Sale of Tabloids. PMID- 29004104 TI - A Question of Medical Attendance. PMID- 29004105 TI - Five Cases of Quartan Fever. PMID- 29004106 TI - The Entero-Coccus of Dysentery. PMID- 29004108 TI - Pernicious Malaria or Surra in Animals. PMID- 29004109 TI - Foreign Extract. PMID- 29004107 TI - Fourteen Cases of Cerebro-Spinal Fever. PMID- 29004110 TI - The Reappearance of Epidemic Dropsy in Calcutta. PMID- 29004111 TI - Some Cases of Malignant Pustule. PMID- 29004112 TI - On the Use of Lead Plate in Simple Ulcer, and of Sandbag in Bubo. PMID- 29004114 TI - Herpes Labialis in Acute Pneumonia. PMID- 29004113 TI - Cases in S. Stephen's Mission Hospital, Delhi. PMID- 29004116 TI - London Letters. PMID- 29004115 TI - Note on Assendelft's Work on Stone. PMID- 29004118 TI - Current Topics. PMID- 29004117 TI - The Bengal Chemical Examiner's Report. PMID- 29004119 TI - Mulroney's Operation. PMID- 29004120 TI - Colonel G. C. Hall, I.M.S., on Cataract. PMID- 29004121 TI - The Operation of Extraction in 1866. PMID- 29004122 TI - A Modification of Priestley Smith's Perimeter. PMID- 29004123 TI - Cataract Extraction at Bombay. PMID- 29004124 TI - The Bombay Ophthalmic Hospital. PMID- 29004125 TI - Senile Cataract as a Cause of Glaucoma. PMID- 29004127 TI - Drake-Brockman's Operation: Primary Capsule Rupture. PMID- 29004126 TI - Extraction of Cataract in the Capsule. PMID- 29004128 TI - Macnamara on Linear Extraction. PMID- 29004129 TI - Drake-Brockman's Review of 1,626 Cases of Cataract Extraction. PMID- 29004130 TI - The Older Operations in the Madras Eye Infirmary. PMID- 29004131 TI - Cataract in Kashmir. PMID- 29004132 TI - Practical Points in Cataract Extraction. PMID- 29004134 TI - On Cataract and Its Extraction. PMID- 29004133 TI - Ophthalmic Notes from Mozufferpur. PMID- 29004135 TI - The Calcutta Ophthalmic Hospital. PMID- 29004137 TI - Ophthalmology at the Calcutta Medical Congress. PMID- 29004136 TI - Eye Operations at Azamgarh. PMID- 29004138 TI - The Madras Eye Infirmary. PMID- 29004139 TI - Notice to Contributors. PMID- 29004140 TI - Dr. Sanders' Methods at the Calcutta Eye Hospital. PMID- 29004141 TI - Cataract and Its After-Treatment. PMID- 29004142 TI - Three Hundred Consecutive Cases, Analysis of. PMID- 29004143 TI - Ophthalmic Notes. PMID- 29004144 TI - Cataract at Jaipur. PMID- 29004145 TI - T. H. Pope on Cataract in the Madras Presidency. PMID- 29004147 TI - The Alleged Susceptibility of the Goorkhas to Tubercle. PMID- 29004146 TI - The Great Medicinal Value of Plant Lygodinum Pinnatifidum. PMID- 29004150 TI - Surgical Cases from the Sambhu Nath Pundit Hospital. PMID- 29004149 TI - Plague Detected Post-Mortem. PMID- 29004151 TI - On Reparative Operations for the Cure of Oblique Inguinal Hernia. PMID- 29004152 TI - Stricture of the Urethra: Lectures Delivered at the Medical Graduates' College, London, November 1900. PMID- 29004154 TI - Current Topics. PMID- 29004153 TI - Elephantiasis of Scrotum. PMID- 29004156 TI - Service Notes. PMID- 29004155 TI - Note on a New Method of Treating Malaria. PMID- 29004157 TI - Lime Juice in Malarial Fever. PMID- 29004158 TI - Supra-Renal Extract in Heart-Disease. PMID- 29004159 TI - The Tropical Section, B. M. A. PMID- 29004160 TI - Transposition of Viscera. PMID- 29004161 TI - The Causes of Hydrocele. PMID- 29004162 TI - Major Bannerman, I.M.S., on Four Years' Inoculations against Plague. PMID- 29004163 TI - Intestinal Parasites. PMID- 29004164 TI - Flagellar Fever in Tertian. PMID- 29004165 TI - London Letters. PMID- 29004166 TI - Beri-Beri among Tamils in Rangoon. PMID- 29004167 TI - Prophylaxis of Small-Pox. PMID- 29004168 TI - Black-Water Fever in Duars. PMID- 29004169 TI - Dry Gangrene after Cholera. PMID- 29004170 TI - Tetanus Puerperalis. PMID- 29004171 TI - Ophthalmic Work in India. PMID- 29004173 TI - Current Topics. PMID- 29004172 TI - Silting up of River and Malaria, &c. PMID- 29004174 TI - Stone Cases at Durbhanga. PMID- 29004176 TI - Medical Society: The Bombay Medical and Physical Society. PMID- 29004175 TI - Involuntary Iridectomy. PMID- 29004177 TI - Appendicitis in Bengal. PMID- 29004178 TI - Therapeutic Preparations, &c. PMID- 29004179 TI - Cocaine-Eating in Calcutta. PMID- 29004180 TI - Suggestions for Improvement of a Field Hospital Section. PMID- 29004181 TI - Parasites in Anopheles. PMID- 29004183 TI - Snake-Bite and Antivenene. PMID- 29004182 TI - London Letters. PMID- 29004184 TI - The "Nordrach" Treatment of Tubercle. PMID- 29004185 TI - Sword Wounds of the Head. PMID- 29004187 TI - Case of Supra-Public Lithotomy. PMID- 29004186 TI - A Year's Experience of Anopheles in Ellichpur. PMID- 29004189 TI - Rupture of Uterus (Spontaneous ?). PMID- 29004188 TI - Salol in Small-Pox. PMID- 29004190 TI - Service Notes. PMID- 29004191 TI - Beri-Beri in Tamils. PMID- 29004192 TI - Anopheles Funestus and Costalis in Duars. PMID- 29004193 TI - Litholapaxy. PMID- 29004194 TI - Encysted Stone in Bladder. PMID- 29004195 TI - Bacteriological Report on Cerebro-Spinal Fever. PMID- 29004197 TI - Medical Progress in Bombay. PMID- 29004196 TI - Stricture at the Meatus-Complete Retention of Urine. PMID- 29004198 TI - Notes on the History of the Bengal Medical Service. PMID- 29004199 TI - Report on Cerebro-Spinal Fever. PMID- 29004200 TI - Bone Affections in Yaws. PMID- 29004201 TI - Case of Snake-Bite Treated with Calmette's Antivenine Recovery. PMID- 29004203 TI - London Letters. PMID- 29004202 TI - Beri-Beri in the Northern Circars. PMID- 29004204 TI - The Dhoti as a Cause of Hydrocele. PMID- 29004205 TI - Current Topics. PMID- 29004207 TI - Calculi in Kidneys and Ureters. PMID- 29004206 TI - Memoirs of Edward Hare, Inspector-General of Hospitals. PMID- 29004208 TI - A Case of Lumbar Hernia in a Child. PMID- 29004209 TI - Service Notes. PMID- 29004210 TI - A Strange Tumour. PMID- 29004211 TI - The Registration of Operations for Stone. PMID- 29004213 TI - Medical Progress in India in the past Century. PMID- 29004212 TI - A Twenty-Two Ounce Stone in Bladder. PMID- 29004214 TI - Oriental Sore. PMID- 29004215 TI - Influenzal Pneumonia. PMID- 29004216 TI - Case of Remittent (?) Fever. PMID- 29004217 TI - Ophthalmic Complications of Plague. PMID- 29004218 TI - Cases of Scurvy from China. PMID- 29004220 TI - London Letters. PMID- 29004219 TI - The American Hospital Ship Relief. PMID- 29004221 TI - A Veldt Sore. PMID- 29004222 TI - Corrigenda. AB - [This corrects the article on p. 291 in vol. 36.]. PMID- 29004223 TI - Service Notes. PMID- 29004224 TI - A Case of Wound Diphtheria Treated by Ecthol. PMID- 29004225 TI - Therapeutic Preparations. PMID- 29004226 TI - Beri-Beri on the Surveying Ships. PMID- 29004229 TI - Amputation through Trochanters. PMID- 29004227 TI - Beri-Beri in China Force. PMID- 29004228 TI - Litholapaxy v. the Suprapubic Operation. PMID- 29004230 TI - Rational and Safe Treatment of Obesity. PMID- 29004231 TI - The Prevalent Diseases in Peking. PMID- 29004232 TI - Current Topics. PMID- 29004233 TI - Case of Penetrating Wound of Abdomen: Recovery. PMID- 29004235 TI - Malingering in Indian Prisons. PMID- 29004234 TI - Cattle Plague in China. PMID- 29004236 TI - Freyer's Operation for Total Extirpation of the Prostate. PMID- 29004238 TI - Experimental Inoculation of Malarial Fever. PMID- 29004237 TI - Service Notes. PMID- 29004239 TI - An Account of Ophthalmic Practice in Russia. PMID- 29004240 TI - Is the Gurkha Predisposed to Pulmonary Phthisis? PMID- 29004241 TI - Surgical Cases from the Sambhu Nath Pandit Hospital, Bhowanipur, Calcutta. PMID- 29004242 TI - Current Topics. PMID- 29004243 TI - A Case of Intracranial Neurectomy of the Fifth Nerve. PMID- 29004244 TI - Cholera in Madhubani. PMID- 29004245 TI - The New Constitution of the B. M. Association. PMID- 29004246 TI - Hydrocele and Its Causes. PMID- 29004247 TI - The Distribution of Mosquitos in Ellichpur: For the I. M. G. Collective Investigation. PMID- 29004249 TI - The Bombay Medical Society: Plague Treatment with Lustig's Serum. PMID- 29004248 TI - Ankylostoma Duodenale in Darbhanga: For the I. M. G. Collective Investigation. PMID- 29004250 TI - The Body Temperature of the European and Native in India, with Special Reference to the Gurkha. PMID- 29004252 TI - The Serums of Viper and Cobra. PMID- 29004251 TI - A Sporozoon Found in Human Blood. PMID- 29004254 TI - London Letters. PMID- 29004253 TI - Typhoid Fever in Natives. PMID- 29004256 TI - African and Indian Malaria Compared. PMID- 29004255 TI - Three Cases of Snake-Bite and Antivenene. PMID- 29004257 TI - Observations on 235 Cataract Cases. PMID- 29004258 TI - Current Topics. PMID- 29004259 TI - Ophthalmic Notes from Midnapur. PMID- 29004260 TI - Tobacco Amblyopia, and Optic Atrophy in Beri-Beri. PMID- 29004261 TI - Ophthalmic Notes from Chapra. PMID- 29004262 TI - Professor Koch and His Critics. PMID- 29004263 TI - The Bombay Medical and Physical Society. PMID- 29004264 TI - London Letters. PMID- 29004265 TI - Cataract at Bhagalpore. PMID- 29004266 TI - Further Experiments on Cause of Beri-Beri. PMID- 29004267 TI - Malignant Tertian Fever. PMID- 29004268 TI - A Case of Diphtheria. PMID- 29004269 TI - Irrigation of Anterior Chamber. PMID- 29004270 TI - Eye-Diseases in Kashmir. PMID- 29004272 TI - Cataract Notes. PMID- 29004271 TI - Service Notes. PMID- 29004273 TI - The Action of Atropine. PMID- 29004276 TI - A New Eye Speculum. PMID- 29004274 TI - Field of Vision in Hysteria. PMID- 29004277 TI - The Dysentery of English Asylums: A Revelation. PMID- 29004278 TI - Surgical Cases from the Sambhu Nath Pandit Hospital, Bhowanipur, Calcutta. PMID- 29004279 TI - Cataract Operations. PMID- 29004281 TI - Biological Sewage Purification for India. PMID- 29004280 TI - Ophthalmic Notes from Berhampur. PMID- 29004283 TI - A Case of Continued Fever (Remittent Fever? Enteric Fever?). PMID- 29004282 TI - Rheumatism and Dysentery. PMID- 29004284 TI - Serum Treatment of Plague. PMID- 29004285 TI - London Letter. PMID- 29004286 TI - Abstract of a Paper on the Relationship of Drinking Water;- Water-Logging and the Distribution of Anopheles Mosquitoes Respectively to the Prevalence of Malaria North of Calcutta: From the Proceedings of the Asiatic Society, Read before the Asiatic Society of Bengal, July 1900. PMID- 29004287 TI - Current Topics. PMID- 29004288 TI - Interesting Case of Fracture of the Skull. PMID- 29004289 TI - Notes on Beri-Beri in Rangoon. PMID- 29004290 TI - Extracts from Foreign Medical Journals. PMID- 29004291 TI - On the Metamorphosis of the Filaria Sanguinis Hominis in Mosquitoes, Especially with Reference to Its Metamorphosis in the Anopheles Rossii and Other Mosquitoes of the Anopheles Genus. PMID- 29004292 TI - A Garbled Quotation. PMID- 29004293 TI - Service Notes. PMID- 29004294 TI - The Treatment of Gonorrhoea by Injections of Cocaine and Nitrate of Silver. PMID- 29004295 TI - A Case of Hernia in the Right Hypochondriac Region. PMID- 29004296 TI - A Case of Acute Yellow Atrophy of the Liver. PMID- 29004297 TI - An Operation for the Total Excision of Tonsils. PMID- 29004298 TI - Experiences in Tubercular Disease. PMID- 29004299 TI - Sarcoma of the Testicle. PMID- 29004300 TI - Bite of an Echis Carinata. PMID- 29004301 TI - A Case of Intraperitoneal Rupture of the Bladder. PMID- 29004302 TI - Plague Pneumonia: Its Bearing on Recent Controversies and Existing Preventive Measures Also a Personal Statement. PMID- 29004303 TI - Correspondence. PMID- 29004304 TI - Papillomatous Overgrowth of Both Tonsils. PMID- 29004306 TI - The Action of Creasote in Reducing High Temperature in Enteric Fever. PMID- 29004305 TI - Melancholia in Its Relations to Homicide. PMID- 29004308 TI - Medical Section of the Asiatic Society of Bengal. PMID- 29004307 TI - Current Topics. PMID- 29004309 TI - On Some Old Eighteenth Century Lists of the I. M. S. PMID- 29004311 TI - Purification of Tank and Well Water. PMID- 29004310 TI - Encysted Stone in Urethra. PMID- 29004312 TI - Service Notes. PMID- 29004313 TI - Remarks upon the Indian Snake-Bite Records Which Appear in Calmette's Recent Work. PMID- 29004314 TI - Reform or Reduction. PMID- 29004316 TI - Notes from the Hughli Hospitals, 1903 - 1909. PMID- 29004315 TI - Jail Dysentery, with Special Reference to Forster's Vaccine. PMID- 29004317 TI - Incarceration of a Retro-Deviated Pregnant Uterus: Re-Opening of a Partially Obliterated Urachus. PMID- 29004318 TI - Case for Diagnosis. PMID- 29004319 TI - A New Lactic Acid Producing Streptothrix. PMID- 29004320 TI - The Transmission of Afferent Impulses. PMID- 29004321 TI - On Some Old Eighteenth Century Lists of the I. M. S. PMID- 29004322 TI - Lanoline or Glycerine. PMID- 29004323 TI - Etiology of Double Quotidian Fever with Some Notes on Early Stage of Leishman Donovan Infection. PMID- 29004324 TI - Service Notes. PMID- 29004325 TI - Therapeautic Notes. PMID- 29004326 TI - Current Topics. PMID- 29004328 TI - Quinine Bihydrochloride v. Quinine Bisulphate. PMID- 29004327 TI - Clinical Notes on Small-Pox. PMID- 29004329 TI - The Campaign against Microbes. PMID- 29004330 TI - Blackwater Fever and Quinine. PMID- 29004331 TI - Survivors of the Punjab Campaigns. PMID- 29004332 TI - Beri-Beri. PMID- 29004333 TI - I. M. S. Dinner in Edinburgh. PMID- 29004334 TI - Abscess of the Lung in a Foetus. PMID- 29004336 TI - Pre-Mutiny Jail Administration. PMID- 29004337 TI - Alypin with Special Reference to Its Hitherto Undescribed Cycloplegic Action. PMID- 29004335 TI - A Case of Sarcoma of Lower Lip. PMID- 29004339 TI - Acidosis and Acid Intoxication. PMID- 29004338 TI - An Atypical Case of Rabies in a Dog. PMID- 29004341 TI - A Burman Bored Well. PMID- 29004340 TI - The Extraction of the Lens in Its Capsule (Smith's Operation) by Division of the Suspensory Ligament. PMID- 29004342 TI - Cataract Operations in Outlying Dispensaries. PMID- 29004344 TI - Corrigendum. AB - [This corrects the article on p. 201 in vol. 44.]. PMID- 29004343 TI - Malarial Prevention. PMID- 29004345 TI - Sarcoma of the Femur. PMID- 29004347 TI - The XVI International Medical Congress. PMID- 29004346 TI - Malaria in India: What Can the State Do to Prevent It? PMID- 29004348 TI - The Calcutta Medical Journal. PMID- 29004349 TI - Studies Regarding Pathogenic Amoebae. PMID- 29004350 TI - Service Notes. PMID- 29004352 TI - Current Topics. PMID- 29004351 TI - Special Report of the Medical College Hospital for 1908. PMID- 29004353 TI - On Some Old Eighteenth Century Lists of the I. M. S. PMID- 29004354 TI - Experiences of Micrococcus Catarrhalis Infection. PMID- 29004355 TI - Nastin. PMID- 29004356 TI - Report on an Outbreak of Cholera. PMID- 29004357 TI - The Self-Constituted Private Medical Institutions in Calcutta. PMID- 29004358 TI - Current Topics. PMID- 29004359 TI - A Case of Successful Suture of Both Femoral Artery and Vein in Hunter's Canal for Traumatic Aneurism. PMID- 29004360 TI - A Case of Relapsing Fever in the Central Provinces. PMID- 29004362 TI - Phagedaenic Ulcers in Assam. PMID- 29004361 TI - Cataract Operations in Outlying Dispensaries. PMID- 29004363 TI - Service at Netley. PMID- 29004364 TI - Service Notes. PMID- 29004365 TI - Sporadic Kala Azar in Behar. PMID- 29004367 TI - Notes on Surgical Cases in the David Sassoon General Hospital, Poona. PMID- 29004366 TI - An Old Book. PMID- 29004368 TI - Sanatorium Treatment for Tubercular Cases in India. PMID- 29004369 TI - The Medical Administration Reports. PMID- 29004370 TI - Chloroform Poisoning. PMID- 29004372 TI - Prostatectomy. PMID- 29004373 TI - Date of Service for Pension Grievance. PMID- 29004374 TI - The Theory of Colour Vision. PMID- 29004375 TI - Enteric Fever in Infancy. PMID- 29004371 TI - A Case of Congenital Absence of Both Upper Extremities. PMID- 29004376 TI - Delusions in Young People. PMID- 29004377 TI - A Case of Acromegaly. PMID- 29004378 TI - Two Cases of Sigmoidopexy for Prolapse of the Rectum. PMID- 29004379 TI - On Some Old Eighteenth Century Lists of the I. M. S. PMID- 29004381 TI - Creosote in High Temperatures. PMID- 29004380 TI - A Case of Partial Placenta Praevia with Arm Presentation. PMID- 29004383 TI - Abdomen Torn Open : Recovery. PMID- 29004382 TI - Current Topics. PMID- 29004384 TI - Trachoma Also Occlusion of the Pupil. PMID- 29004386 TI - Notes from the Hughly Hospital, 1903-1909. PMID- 29004387 TI - Report on the Recent Cholera Outbreak among the Nurses of the Presidency General Hospital, Calcutta. PMID- 29004388 TI - The Extraction of the Lens in Its Capsule (Smith's Operation) by Division of the Suspensory Ligament. PMID- 29004389 TI - Service Notes. PMID- 29004390 TI - The New Factory Act. PMID- 29004391 TI - Clinical Notes on Small-Pox. PMID- 29004392 TI - Preliminary Note on Increased Intra-Ocular Tension Met with in Cases of Epidemic Dropsy. PMID- 29004393 TI - An Indian Screw-Worm. PMID- 29004394 TI - August Meeting of the Medical Section of the Asiatic Society of Bengal. PMID- 29004395 TI - Service at Netley. PMID- 29004397 TI - Leave and Furlough in the I.M.S. PMID- 29004396 TI - Leave in the Burma Medical Service. PMID- 29004399 TI - Complimentary Dinner to Lieut.-Col., Mrs. Harris and Miss Harris on Their Departure from the Medical College., Calcutta. PMID- 29004401 TI - Widows' Pensions. PMID- 29004398 TI - Research Defence Society. PMID- 29004400 TI - The Indications and Technique of Transfusion in Cholera, with a Note on Cholera in Europeans in Calcutta. PMID- 29004403 TI - The New Factory Act. PMID- 29004402 TI - Service Notes. PMID- 29004404 TI - Encysted Stone in the Urethra. PMID- 29004405 TI - Experiences with the Lactic Acid Baci Lus. PMID- 29004406 TI - Litholapaxy in Young Children with Suggestions for a Modified Evacuating Apparatus. PMID- 29004407 TI - Notes of Seven Consecutive Cases of Cysts, Operated on at Lady Aitchison Hospital. PMID- 29004408 TI - Cuban Medical Department. PMID- 29004409 TI - Two Cases of Pneumocele of the Lachrymal Sac. PMID- 29004411 TI - Lithotrity and Litholapaxy. PMID- 29004412 TI - Current Topics. PMID- 29004410 TI - Supplement to the Indian Medical Gazette. November, 1909. PMID- 29004413 TI - Cases of Myiasis in Northern India. PMID- 29004414 TI - Common Sense Sanitation. PMID- 29004415 TI - The Lucknow Medical College. PMID- 29004416 TI - Note on 100 Consecutive Cases Operated on under Spinal Analgesia. PMID- 29004417 TI - Fibrolysin in Valvular Disease. PMID- 29004418 TI - Some Old Eighteenth Century List of the I. M. S. PMID- 29004419 TI - Relapsing Fever and the Louse. PMID- 29004420 TI - Small Incinerators. PMID- 29004422 TI - I. M. S. Dress Regulations. PMID- 29004421 TI - Note on the Purification of Native Sewage under Defined Conditions. PMID- 29004423 TI - Transmission of Plague in the Absence of Rats. PMID- 29004424 TI - Medical Societies. PMID- 29004425 TI - Nervous Breakdown as Observed in Burma. PMID- 29004426 TI - To Old Guy's Men. PMID- 29004427 TI - Clinical Report on the Berhampore Asylum for the Year 1909. PMID- 29004429 TI - Current Topics. PMID- 29004428 TI - Smith's Operation for Cataract. PMID- 29004430 TI - Thevetia Poisoning. PMID- 29004431 TI - Lanoline or Glycerine. PMID- 29004432 TI - Mosquito or Man? PMID- 29004433 TI - Sleeping Sickness in Uganda. PMID- 29004434 TI - Lens Couching in India. PMID- 29004436 TI - Service Notes. PMID- 29004435 TI - The Malaria Laboratory, Amritsar. PMID- 29004438 TI - Medical Societies. PMID- 29004437 TI - Lt.-Colonel Smith's Operations in Bombay. PMID- 29004439 TI - Sclerectomy in Glaucoma. PMID- 29004440 TI - Tubercle of the Lung in Hughli. PMID- 29004441 TI - Smith's Operation for Cataract. Two New Instruments. PMID- 29004442 TI - The Diagnosis of Typhoid Fever. PMID- 29004443 TI - The Treatment of Filaria Medinensis. PMID- 29004444 TI - Simple Trephining in the Operative Treatment of Glaucoma. PMID- 29004445 TI - Placenta Praevia. PMID- 29004447 TI - Formaldehyde and Flies. PMID- 29004446 TI - Camphor Poisoning. PMID- 29004448 TI - Extraction of Cataract in the Capsule. PMID- 29004450 TI - Service Notes. PMID- 29004449 TI - A Case of Myrasis. PMID- 29004452 TI - The Health of Indians in Natal. PMID- 29004451 TI - A Case of Hymenolepis Nana. PMID- 29004453 TI - Current Topics. PMID- 29004454 TI - Despotic Hygiene at Panama. PMID- 29004455 TI - The I.S.M.D. and British Qualifications. PMID- 29004457 TI - Current Topics. PMID- 29004456 TI - The Ipecacuanha Treatment of Acute Hepatitis. PMID- 29004458 TI - Effect of Ipecacuanha on the Leucocyte Curve in Amoebic Hepatitis. PMID- 29004459 TI - The Ipecacuanha Treatment of Acute Hepatitis. PMID- 29004460 TI - Service Notes. PMID- 29004461 TI - The Isolation Wards. PMID- 29004463 TI - Military Medical Notes. PMID- 29004462 TI - Lithotrity and Litholapaxy. PMID- 29004464 TI - Some Common Operations in India. PMID- 29004465 TI - The Ipecacuanha Treatment of Acute Hepatitis. PMID- 29004466 TI - Major Kilkelly's Reply to Lieut.-Colonel H. Smith. PMID- 29004467 TI - Ipecacuanha in the Treatment of Acute Hepatitis. PMID- 29004469 TI - Report for 1909 of Medical College Hospital, Calcutta. PMID- 29004468 TI - Continental Watering Places. PMID- 29004471 TI - Service Notes. PMID- 29004470 TI - Notes on the Ipecacuanha Treatment of Hepatitis. PMID- 29004472 TI - An Extraordinary Series of Outbreaks of Plague in Cape Colony. Due to Case to Case Infection. PMID- 29004474 TI - Surgical Cases. PMID- 29004473 TI - British Qualifications for I. S. M. Dept. PMID- 29004475 TI - Eclampsia and Puerperal Mania. PMID- 29004477 TI - Current Topics. PMID- 29004476 TI - Experiences in the Treatment of Stricture of the Urethra. PMID- 29004478 TI - A Case of Hydrophobia. PMID- 29004479 TI - Annus Medicus. PMID- 29004480 TI - Twenty-One-Day-Fever in Children. PMID- 29004481 TI - Smith's Operation of Extraction of the Lens in Its Capsule. PMID- 29004482 TI - Tubercle, but Where Was the Lesion? PMID- 29004483 TI - Extraction of Lens in Capsule. PMID- 29004485 TI - The Minor Medical Services. PMID- 29004484 TI - Bacteriology of Water Supplies. PMID- 29004486 TI - An Operation for Varicose Veins. PMID- 29004488 TI - Three Cases of Hydatid Cyst Situate in the Eye or in the Orbit. PMID- 29004487 TI - Lalor's Tourniquet. PMID- 29004489 TI - Burma Branch of B. M. A. PMID- 29004490 TI - Bishop's Retractor for Lacrymal Sac. PMID- 29004491 TI - X-Ray Notes. PMID- 29004492 TI - Smith's Operation. PMID- 29004493 TI - Ascariasis. PMID- 29004494 TI - The Medical Service in Campaigns. PMID- 29004495 TI - Service Notes. PMID- 29004496 TI - Varieties of Dwarfs. PMID- 29004497 TI - Smith's Cataract Operation. PMID- 29004498 TI - Medical Societies. PMID- 29004499 TI - Difficult Case of Labour. PMID- 29004500 TI - Case of Snake-Bite. PMID- 29004502 TI - Hernia Operations. PMID- 29004501 TI - Ascariasis, Letters on. PMID- 29004503 TI - Current Topics. PMID- 29004505 TI - Intestinal Obstruction Caused by Tapeworm. PMID- 29004504 TI - Hiccough and Cholera. PMID- 29004506 TI - On Mounting Mosquitoes. PMID- 29004507 TI - Teaching of Protozoology. PMID- 29004508 TI - Treatment of Cholera. PMID- 29004509 TI - Case of Snake-Bite. PMID- 29004510 TI - Remarks on Ascariasis, Is There a Round Worm Fever? PMID- 29004511 TI - Blackwater Fever. PMID- 29004512 TI - Pelvic Diseases. PMID- 29004513 TI - Smith's Reply to Kilkelly. PMID- 29004515 TI - A Case of Hypertrophic Pulmonary Osteo-Arthropathy. PMID- 29004514 TI - Poisoning by Eucalyptus. PMID- 29004516 TI - Note on the Causation of Diseases of the Heart and Aorta in Europeans in India. PMID- 29004517 TI - Case of Foreign Body (Bottle) in the Rectum. PMID- 29004518 TI - Transposition of the Viscera. PMID- 29004519 TI - A Note on the Technique of Intracapsular Extraction. PMID- 29004520 TI - Gleanings from the Calcutta Post-Mortem Records. PMID- 29004521 TI - Epilepsy, Nocturnal. PMID- 29004522 TI - Service Notes. PMID- 29004523 TI - Treatment of Relapsing Fever by Intramuscular Injections of Orsudon. PMID- 29004525 TI - Type of Plague. PMID- 29004524 TI - The Prevention of Hydrophobia. PMID- 29004526 TI - Couchers and Their Methods. PMID- 29004527 TI - Transmission of Plague in the Absence of Rats and Rat Fleas. PMID- 29004529 TI - Current Topics. PMID- 29004528 TI - Myiasis in Burma. PMID- 29004530 TI - The Medical Services in 1909. PMID- 29004531 TI - Unusual Type of Plague. PMID- 29004532 TI - Doctors in Parliament. PMID- 29004533 TI - Is Thymol a Panacea? PMID- 29004535 TI - Imperial Malaria Conference at Simla. PMID- 29004534 TI - Dengue or Phlebotomus Fever. PMID- 29004536 TI - Note on a Sign of Chronic Malarial Poisoning. PMID- 29004537 TI - A Case of Pneumonia, Terminating in Gangrene. PMID- 29004538 TI - Surgical Operation Returns. PMID- 29004539 TI - Special Snake-Bite Lancet. PMID- 29004540 TI - Lithotrity and Litholapaxy. PMID- 29004541 TI - Health Progress in the West Indies. PMID- 29004542 TI - Painful Heel, with Skiagram. PMID- 29004544 TI - Vaccine Treatment in a Mofussil Hospital. PMID- 29004543 TI - Remarks on Ascariasis. Is There a Round Worm Fever? PMID- 29004545 TI - Notes on Schlosser's Method. PMID- 29004546 TI - The Illegal Trade in Cocaine. PMID- 29004547 TI - Mixed Tumour of the Parotid. PMID- 29004550 TI - The Pathogenesis of Cataract. PMID- 29004549 TI - Sub-Conjunctival Injections of Cyanide of Mercury in Trachomatous Conditions. PMID- 29004548 TI - The Rationale of Quinine Prophylaxis. PMID- 29004551 TI - Leucaemia and Pseudoleucaemia. PMID- 29004552 TI - Foreign Body in the Rectum. PMID- 29004554 TI - Current Topics. PMID- 29004553 TI - Beri-Beri and Rice. PMID- 29004555 TI - Sub-Lingual Calculi. PMID- 29004557 TI - A Case of Biliary Colic. PMID- 29004556 TI - A Screw-Worm beneath the Conjunctiva. PMID- 29004559 TI - Service Notes. PMID- 29004558 TI - Kala Azar in Patna. PMID- 29004560 TI - Colipyelitis. PMID- 29004561 TI - Enlarged Prostate. PMID- 29004562 TI - An Extraordinary Series of Outbreaks of Plague. PMID- 29004563 TI - Widows' Pensions. PMID- 29004564 TI - Perirenal Abscess. PMID- 29004565 TI - Death from Intraspinal Injection of Novocaine and Strychnine. PMID- 29004567 TI - Pseudo-Hypertrophic Muscular Paralysis. PMID- 29004566 TI - Current Topics. PMID- 29004568 TI - Ventro-Fixation of the Uterus: A Protest. PMID- 29004569 TI - Electric Burns. PMID- 29004570 TI - Circulatory Diseases in India. PMID- 29004571 TI - Indicanuria and Its Significance. PMID- 29004572 TI - Case of Cobra-Bite. PMID- 29004573 TI - Sarcoma of Lower Jaw. PMID- 29004574 TI - Acute Scurvy. PMID- 29004575 TI - Lanoline or Glycerine. PMID- 29004576 TI - Preparation of Hands and Skin. PMID- 29004577 TI - Accelerated Promotion. PMID- 29004578 TI - On the Occurrence of an Epizootic of Fowl Septicaemia. PMID- 29004580 TI - Service Notes. PMID- 29004579 TI - The Retiring Director-General. PMID- 29004581 TI - Congenital Absence of Uterus and Vagina. PMID- 29004583 TI - Extracts from Medical History Sheets, 69th Punjabis. PMID- 29004582 TI - Medico-Legal Practice in the Mofussil. PMID- 29004584 TI - A Note on the Administration of Quinine in Cases of Fever during Pregnancy. PMID- 29004585 TI - Operations for Varicose Veins. PMID- 29004586 TI - Kenil Calculus in Calcutta. PMID- 29004587 TI - Current Topics. PMID- 29004588 TI - Urticaria in Connection with Malaria. PMID- 29004589 TI - Gleanings from the Calcutta Post-Mortem Records. PMID- 29004591 TI - Lithotrity and Litholapaxy. PMID- 29004590 TI - Note on Cases of the "Epidemic Dropsy". PMID- 29004592 TI - Retirement of Lieutenant-Colonel Gimlette, I.M.S. PMID- 29004593 TI - Medical Registration. PMID- 29004594 TI - Supplement to "The Indian Medical Gazette." April, 1910. PMID- 29004595 TI - Therapeutic Uses of Boerhaavia Diffusa (Linn.). PMID- 29004596 TI - A Useful Service Book. PMID- 29004597 TI - Service Notes. PMID- 29004598 TI - Enteric Fever in Baghdad. PMID- 29004599 TI - A Case of Staphylococcal Cerebro-Spinal Meningitis. PMID- 29004601 TI - Elephantiasis Treated by the Implantation of Silk Sutures as Artificial Lymphatics. PMID- 29004600 TI - The Echis Carinata Bite. PMID- 29004602 TI - Organisation of Abdominal Operations: Part II. PMID- 29004603 TI - The Advance of Surgery in India. PMID- 29004604 TI - Surgical Tuberculosis. PMID- 29004605 TI - Operations for Hernia. PMID- 29004607 TI - Opium Question in China. PMID- 29004606 TI - Total Hysterectomy. PMID- 29004608 TI - Organisation and Management of Abdominal Operations: Part I. PMID- 29004609 TI - The Ideal Operation for Fistula in Ano. PMID- 29004611 TI - The I. S. M. D. PMID- 29004610 TI - Surgery of the Pelvic Organs. PMID- 29004613 TI - Urethral Surgery. PMID- 29004612 TI - Enlargement of the Prostate. PMID- 29004614 TI - Sterilisation of Skin by Iodine. PMID- 29004616 TI - Septic Phlebitis of Spermatic Cord. PMID- 29004615 TI - Remarks on Appendicitis. PMID- 29004617 TI - Service Notes. PMID- 29004618 TI - Seven-Day-Fever. PMID- 29004619 TI - The Military Medical Department. PMID- 29004621 TI - Treatment of Acute Peritonitis. PMID- 29004620 TI - Some Notes on Tumour and Intestinal Obstruction. PMID- 29004622 TI - "Rogers" Seven-Day-Fever. PMID- 29004623 TI - Penetrating Wounds of the Abdomen. PMID- 29004624 TI - The Operative Treatment of Hydrocele. PMID- 29004625 TI - Current Topics. PMID- 29004626 TI - The Ethical Teaching of Lanfrank. PMID- 29004627 TI - The Operation Theatre. PMID- 29004628 TI - A Master-Surgeon of the 14th Century. PMID- 29004629 TI - The Contents of a Hernia. PMID- 29004630 TI - Urticaria and Malaria. PMID- 29004631 TI - Hydatid Cyst of the Orbit. PMID- 29004632 TI - Experiments on the Intravenous Injection of Permanganates for Snake-Bite. PMID- 29004633 TI - Vaccination in India. PMID- 29004634 TI - Treatment of Snake-Bite with Potassium Permanganate. PMID- 29004635 TI - The Indian Oculist, His Equipment and Methods. PMID- 29004637 TI - Surgical Operation Returns. PMID- 29004636 TI - A Case of Rupture of Spleen. PMID- 29004638 TI - Technique of the Hypodermic Injection. PMID- 29004639 TI - Ophthalmic Reaction in Early Phthisis. PMID- 29004640 TI - Current Topics. PMID- 29004641 TI - A New Combined Needleholder and Scissors. PMID- 29004642 TI - Retro-Ocular Neuritis. PMID- 29004643 TI - Service Notes. PMID- 29004644 TI - Tropo-Ratine. PMID- 29004645 TI - Chronic Malarial Poisoning. PMID- 29004647 TI - Dermoid Cyst. PMID- 29004646 TI - British Medical Association Meeting. PMID- 29004648 TI - Lithotrity and Litholapaxy. PMID- 29004650 TI - Medical Education in India. PMID- 29004649 TI - A Haemophilic Pedigree. PMID- 29004651 TI - Malaria in Bombay. PMID- 29004652 TI - Bottle in Rectum. PMID- 29004653 TI - Beri-Beri and a Lack of Phosphorus. PMID- 29004655 TI - Operation Rooms in the Tropics. PMID- 29004654 TI - Four Common Surgical Operations in India. PMID- 29004656 TI - Medical Societies. PMID- 29004657 TI - Dysentery and Tubercle. PMID- 29004658 TI - Sanitation in the Hills. PMID- 29004659 TI - Punjab Plague Committee's Report. PMID- 29004660 TI - Treatment of Syphilis at Aix-La-Chapelle. PMID- 29004661 TI - The Claims of Penology. PMID- 29004662 TI - Current Topics. PMID- 29004663 TI - Rupture of Kidney. PMID- 29004664 TI - Plague Problems. PMID- 29004665 TI - Suction of Abscesses. PMID- 29004666 TI - Sandfly Fever. PMID- 29004668 TI - Service Notes. PMID- 29004667 TI - The Bombay Cataract Cases. PMID- 29004669 TI - Treatment of Cholera. PMID- 29004670 TI - Use of Quinine. PMID- 29004671 TI - Gynaecological Coeliotomy. PMID- 29004672 TI - Liver Abscess. PMID- 29004673 TI - Service Notes. PMID- 29004674 TI - Case of Multiple Keloids Following Small-Pox. PMID- 29004675 TI - An Influenza-Like Fever in Calcutta. PMID- 29004676 TI - Vital Statistics, I. M. S. PMID- 29004678 TI - A Case for Diagnosis. PMID- 29004677 TI - Wasp Sting. PMID- 29004680 TI - Trichiasis, Entropion and Tinea Tarsi. PMID- 29004679 TI - Enchrondroma of Parotid Gland. PMID- 29004681 TI - The New Rates of Pay for the Jail Department. PMID- 29004682 TI - Tropical Light and White Men. PMID- 29004683 TI - Gunshot Wound of Bladder. PMID- 29004684 TI - How to Cure Cholera. PMID- 29004685 TI - Editorial Notes on Current Topics. PMID- 29004686 TI - Tumour of Brain. PMID- 29004688 TI - New Views on Malaria. PMID- 29004687 TI - Cases from Madras General Hospital. PMID- 29004689 TI - Case of Chyluria. PMID- 29004690 TI - Plague in Animals. PMID- 29004691 TI - Poisoning by Strychnine: Recovery. PMID- 29004692 TI - Opium-Poisoning in a Child. PMID- 29004693 TI - Cataract Extraction in Capsule. PMID- 29004694 TI - Editorial Notes on Current Topics. PMID- 29004695 TI - Service Notes. PMID- 29004696 TI - Malignant Endocarditis. PMID- 29004698 TI - The Anatomy of Plague Buboes. PMID- 29004697 TI - Bactericidal Value of Chlorine and Iodine. PMID- 29004699 TI - Treatment of Cholera by Izal. PMID- 29004700 TI - Pratt's Operation for Hydrocele. PMID- 29004701 TI - Prostatic Enlargement in Natives. PMID- 29004702 TI - Typhoid with Complications. PMID- 29004703 TI - Ovariotomy. PMID- 29004704 TI - Wound of Gravid Uterus. PMID- 29004705 TI - The Epidemiology of Plague. PMID- 29004706 TI - Wound of Abdomen. PMID- 29004707 TI - Ixora in Dysentery. PMID- 29004708 TI - Pott's Fracture. PMID- 29004709 TI - Case of Leishman-Donovan Disease in a European. PMID- 29004710 TI - Traumatic Tetanus. PMID- 29004711 TI - On Hydatids in the Female Pelvis: With Notes of a Case of Primary Hydatid Disease of the Bladder. PMID- 29004712 TI - Sanitation in India. PMID- 29004713 TI - The R. A. Medical College. PMID- 29004715 TI - The Earthquake at Dharmsala. PMID- 29004714 TI - The Colonial Medical Service. PMID- 29004716 TI - The Operation for the Removal of Elephantiasis of the Scrotum and Penis: Notes on Two Hundred Consecutive Cases. PMID- 29004718 TI - Dr. Doyen and Cancer. PMID- 29004717 TI - Notes on the Prevalence of Malignant Disease in Bengal. PMID- 29004719 TI - Cataract Couching. PMID- 29004720 TI - Gastro-Enterotomy for the Relief of Benign Stricture of the Pylorus-With Report of Six Cases. PMID- 29004722 TI - The Cultivation Leishman-Donovan Body. PMID- 29004721 TI - Pemphigus Contagiosus. PMID- 29004723 TI - After-Results of Sixty-Three Operations for Depression of the Lens Performed by Indian "Cataract-Prickers". PMID- 29004725 TI - Service Notes. PMID- 29004724 TI - The Falling Birth-Rate of Great Britain. PMID- 29004726 TI - Helouan as a Health Resort. PMID- 29004727 TI - Medical Cases. PMID- 29004728 TI - Editorial Notes on Current Topics. PMID- 29004729 TI - Some Remarks on Malaria Prophylaxis. PMID- 29004730 TI - Is Cataract Couching Ever Justifiable? PMID- 29004732 TI - Utilising the Appendix Vermiformis. PMID- 29004731 TI - An Account of a Case of Complete Detachment of the Heart. PMID- 29004734 TI - Special Research in India. PMID- 29004733 TI - The University of London and Tropical Medicine. PMID- 29004735 TI - A Pterygium of Bacilli. PMID- 29004736 TI - Poisoning by Sulpho-Cyanide of Mercury. PMID- 29004737 TI - Two Cases of Diphtheria. PMID- 29004738 TI - Some Points Connected with Liver Abscess as Seen in Calcutta. PMID- 29004739 TI - Corrigenda. AB - [This corrects the article on p. 52 in vol. 40.]. PMID- 29004740 TI - The Nature and Prophylaxis of the Fevers in the Dinajpur District. PMID- 29004741 TI - Surgery. PMID- 29004742 TI - An Outbreak of True Beri-Beri among the Students at Tura, Garo Hills, Assam. PMID- 29004743 TI - Oil of Eucalyptus in Cholera. PMID- 29004744 TI - Vaccine Lymphs in the Punjab. PMID- 29004745 TI - Fancy Cures of Snake-Bite. PMID- 29004746 TI - Sanitary Reforms in India. PMID- 29004747 TI - A Case of Perchloride of Mercury Poisoning. PMID- 29004749 TI - Editorial Notes on Current Topics. PMID- 29004748 TI - Service Notes. PMID- 29004750 TI - The Leishman-Donovan Body. PMID- 29004751 TI - Myxoedema in India. PMID- 29004752 TI - The Purification of Water by Copper. PMID- 29004753 TI - Editorial Notes on Current Topics. PMID- 29004754 TI - Farewell to the Indian Medical Gazette. PMID- 29004756 TI - Research in Tropical Diseases in India. PMID- 29004755 TI - Spirillum Fever in India. PMID- 29004757 TI - A Preliminary Paper on Extirpation of the Lachrymal Sac in India. PMID- 29004758 TI - Puerperal Convulsions. PMID- 29004759 TI - Quinine in Pregnancy. PMID- 29004760 TI - Public Health. PMID- 29004761 TI - Obscure Irregular Continued Fevers of the "Typhoid" Group. PMID- 29004763 TI - Is Cataract Couching Ever Justifiable? PMID- 29004762 TI - Primary Carcinoma of the Liver in a Boy of 19 Years. PMID- 29004764 TI - Plague Infection and Flies. PMID- 29004765 TI - A Microbe Agglutinating with Antityphoid Serum. PMID- 29004766 TI - The Last of Netley. PMID- 29004767 TI - Service Notes. PMID- 29004768 TI - The Treatment of Fractures. PMID- 29004769 TI - Tumour of the Left Caudate Nucleus and Frontal Lobe. PMID- 29004772 TI - Nyctalopia in India. PMID- 29004771 TI - Spirillum Fever in India. PMID- 29004770 TI - Two Cases of Pneumococcic Septicaemia with Some Remarks on Pneumonia as Seen on the North-West Frontier. PMID- 29004773 TI - The Bactericidal Power of Nesfield's Method of Water Purification. PMID- 29004774 TI - Malignant Tertian Simulating Plague. PMID- 29004775 TI - Mangoes and Boils. PMID- 29004776 TI - Some Notes on Plague in the Punjab. PMID- 29004777 TI - Enteric Fever in India. PMID- 29004778 TI - Editorial Notes on Current Topics. PMID- 29004779 TI - Fracture of the Skull. PMID- 29004780 TI - Public Health. PMID- 29004782 TI - Medicine. PMID- 29004781 TI - The Significance of the Pyriform Circular and Irregular Shaped Bodies Present in the Circulation, Organs, or Tissues, in Various Forms of Disease in Man and Animals, with Suggestions Regarding Their Identification and Classification. PMID- 29004784 TI - Service Notes. PMID- 29004783 TI - A Series of Sixty-Five Cases of Strangulated Herniae. PMID- 29004785 TI - The Effects of Tropical Light on White Men. PMID- 29004787 TI - The Antiquity of Vaccination in India. PMID- 29004786 TI - Extraction of Cataract in the Capsule. PMID- 29004788 TI - The Relation of Oral Sepsis to Dysentery. PMID- 29004790 TI - Treatment of Dysentery. PMID- 29004789 TI - The Use of Izal in Dysentery. PMID- 29004791 TI - Dysentery: Its Varieties and Causes, Summarised and Criticised with a Note on Treatment and Prevention. PMID- 29004792 TI - A Sling for the Arm. PMID- 29004793 TI - Amoebae and Their Significance. PMID- 29004794 TI - A Chemical Process of Sterilizing Water for Drinking Purposes for Use in the Field and at Home. PMID- 29004795 TI - A Dysentery Toxin and Antitoxin. PMID- 29004796 TI - Dysentery in the Prisons of the Madras Presidency. PMID- 29004798 TI - Amoebic Dysentery in India. PMID- 29004797 TI - The Etiology of Dysentery with Some Notes on Treatment. PMID- 29004800 TI - Progress of Our Knowledge of Dysenteries. PMID- 29004799 TI - Dysentery and Diarrhoea Mortality in the Bombay Presidency. PMID- 29004801 TI - Case of Intestinal Obstruction. PMID- 29004803 TI - Special Dysentery Number. PMID- 29004802 TI - Dysentery as It Occurs in Jails with Regard to Etiology, Prophylaxis and Treatment. PMID- 29004805 TI - The Treatment of Dysentery. PMID- 29004804 TI - Removal of Large Stones in Bladder. PMID- 29004806 TI - The Drug Treatment of Dysentery. PMID- 29004807 TI - Large Stones in the Bladder. PMID- 29004808 TI - Service Notes. PMID- 29004809 TI - The Need for a Medical Library in India. PMID- 29004810 TI - Twelve Cases of Snake-Bite Treated by Incision and Permanganate of Potash; with Ten Recoveries. PMID- 29004811 TI - Viper Bite in a Dog Treated with Permanganate of Potash: Recovery. PMID- 29004813 TI - Litholapaxy, an Unusual Obstacle. PMID- 29004812 TI - The Significance of the Pyriform and Globular Bodies Present in the Circulation and Organs in Various Forms of Disease in Man and Animals with Suggestions Regarding Their Identification and Classification. PMID- 29004815 TI - Radical Cure of Hydrocele. PMID- 29004814 TI - Wharton Hood's Treatment of Injuries. PMID- 29004816 TI - Editorial Notes on Current Topics. PMID- 29004817 TI - Couching for Cataract. PMID- 29004818 TI - Prostatic Enlargement. PMID- 29004819 TI - The Treatment of Cataract in Children. PMID- 29004820 TI - Public Health. PMID- 29004821 TI - Congenital Phimosis with Encysted Preputial Calculi. PMID- 29004822 TI - The Varieties of Bubo Met with in Bubonic Plague and the Rational Treatment of Each Kind. PMID- 29004824 TI - Anti-Malarial Measures, Ancient and Modern. PMID- 29004823 TI - Corrigenda. AB - [This corrects the article on p. 333 in vol. 40.]. PMID- 29004825 TI - Hydrate of Chloral Poisoning. PMID- 29004826 TI - Spontaneous Expulsion of a Vesical Calculus. PMID- 29004827 TI - A Report on the Epidemic of Plague in Hughli-Chinsura Municipality January to May 1905: Abridged from an Official Report. PMID- 29004828 TI - A Case of Recurrent Appendicitis: Operation and Recovery. PMID- 29004830 TI - Septic Tank Installations in Bengal. PMID- 29004829 TI - A Case of Both Kidneys on the Right Side. PMID- 29004831 TI - Service Notes. PMID- 29004832 TI - Notes on the Presence of Spirilla in a Tropical Ulcer. PMID- 29004833 TI - Night-Blindness. PMID- 29004835 TI - The Microbe of Cancer. PMID- 29004834 TI - Surgical Procedure in Liver Abscess. PMID- 29004836 TI - Five Cases of Snake-Bite Successfully Treated by the Local Application of Permanganate of Potash. PMID- 29004837 TI - Correspondence. PMID- 29004838 TI - Sanitary Hair Dressing. PMID- 29004839 TI - Wound of Abdominal Wall-Partial Splenectomy: Recovery. PMID- 29004840 TI - Editorial Notes on Current Topics. PMID- 29004841 TI - A Case of "Missed Abortion". PMID- 29004842 TI - Some Clinical Features of Quartan Malaria. PMID- 29004843 TI - American Sanitary Enterprise in Panama. PMID- 29004844 TI - Plague, Rats and Fleas. PMID- 29004846 TI - The Leishman-Donovan Body. PMID- 29004845 TI - Two Cases of Aneurism. PMID- 29004847 TI - A Factor in the Epidemiology of Plague. PMID- 29004848 TI - Problems for the New Plague Research Committee. PMID- 29004849 TI - Service Notes. PMID- 29004851 TI - Editorial Notes on Current Topics. PMID- 29004850 TI - Hepatic Cirrhosis. PMID- 29004852 TI - Casual Comments. PMID- 29004853 TI - Lens Couching. PMID- 29004854 TI - What Is Hindustani for Scurvy? PMID- 29004855 TI - Malaria Prevention in Madras. PMID- 29004857 TI - Rats and Plague. PMID- 29004856 TI - Death from Haemorrhage in Connection with the Spleen. PMID- 29004858 TI - Some Analogies Which Favour Protozoal Hypotheses of Beri-Beri. PMID- 29004859 TI - A Modified Method of Transplanting a Pterygium. PMID- 29004860 TI - Spirillar Fever in India. PMID- 29004861 TI - Theories of Reclination of Cataract. PMID- 29004862 TI - Orbital Sarcoma: Kronlein's Operation. PMID- 29004863 TI - The Antiquity of Hindu Vaccination. PMID- 29004865 TI - Ear Douche in Plague Deliriium. PMID- 29004864 TI - Gluteal Abscess with Aneurism. PMID- 29004866 TI - Surgical Cases Treated at Arambagh Dispensary. PMID- 29004867 TI - Case of Abscess of the Liver in a Child. PMID- 29004869 TI - Zomotherapy. PMID- 29004870 TI - The Thorough Treatment of Syphilis. PMID- 29004868 TI - Cardiac Failure in Plague and Its Treatment. PMID- 29004871 TI - The Pathology of Cirrhosis of the Liver. PMID- 29004872 TI - Antimosquito Work at St. Lucia. PMID- 29004873 TI - Ambidexterity. PMID- 29004875 TI - A Case of Formalin Poisoning. PMID- 29004874 TI - Service Notes. PMID- 29004876 TI - The Abuse of Hospitals. PMID- 29004877 TI - Copper Sulphate and Disinfection of Water. PMID- 29004878 TI - Colour Vision and Night-Blindness. PMID- 29004880 TI - Preputial Calculus. PMID- 29004879 TI - Treatment of Leprosy by Rost's Leprolin. PMID- 29004881 TI - Case of Sarcoma. PMID- 29004882 TI - Night-Blindness. PMID- 29004883 TI - Primary Vaginal Cancer. PMID- 29004884 TI - Obstetrics. PMID- 29004886 TI - Foreign Extracts. PMID- 29004885 TI - Round Worm Found in Liver. PMID- 29004888 TI - Leprosy. PMID- 29004887 TI - Permanganate and Snake-Bite. PMID- 29004889 TI - Editorial Notes on Current Topics. PMID- 29004890 TI - The Rats of India. PMID- 29004892 TI - The Treatment of Injuries of the Elbow-Joint. PMID- 29004891 TI - Service Notes. PMID- 29004893 TI - Foundation of the Medical College Hospital, Calcutta. PMID- 29004894 TI - Myxoedema in India. PMID- 29004895 TI - Meningo-Myelocele. Operation: Recovery. PMID- 29004896 TI - Mosquitos and Malaria in Ferozepore District, 1903. PMID- 29004897 TI - The Spirit of the Schools of Medicine. PMID- 29004898 TI - Eucalyptus in Cholera. PMID- 29004899 TI - The Doom of Spectacles. PMID- 29004900 TI - A Case of Intestinal Obstruction. Strangulation by the Foetal Remains of the Ophalo-Mesenteric Duct (Meckel's Diverticulum), Operation: Recovery. PMID- 29004901 TI - Fatal Case of Bee Sting. PMID- 29004903 TI - Service Notes from the Great War, 1793-1815. PMID- 29004902 TI - A Case of Snake-Bite (Cobra?): Recovery. PMID- 29004905 TI - Artificial Respiration. PMID- 29004906 TI - Editorial Notes on Current Topics. PMID- 29004904 TI - A Case of Tetanus, Treated by Serum Antitetanique. PMID- 29004908 TI - A Case of Liver Abscess. PMID- 29004907 TI - Myxoedema in India. PMID- 29004909 TI - Medical Society. PMID- 29004910 TI - The Great Value of Inoculation. PMID- 29004911 TI - The Carbuncular Form of Plague. PMID- 29004912 TI - The Surgical Treatment of Chronic Dysentery. PMID- 29004913 TI - A Case of Abscess of the Spleen. PMID- 29004914 TI - Service Notes. PMID- 29004915 TI - Notes on the Distribution of the Two Species of Bed-Bug. PMID- 29004916 TI - Notes on Current Topics. PMID- 29004917 TI - Preputial Calculi. PMID- 29004918 TI - Further Observations on the Use of Adrenalin in Plague. PMID- 29004919 TI - A Case of Cystic Kidney. PMID- 29004920 TI - Appendicitis in Indians. PMID- 29004921 TI - Surgical Curiosities. PMID- 29004922 TI - New Views on Goitre. PMID- 29004923 TI - Service Notes. PMID- 29004925 TI - Extraction of Cataract in the Capsule. PMID- 29004924 TI - Manual of Aseptic Surgery. PMID- 29004927 TI - Service Notes. PMID- 29004926 TI - Some Notes on the Conservancy of the Smaller Towns in Burma. PMID- 29004928 TI - Rheumatism. PMID- 29004930 TI - Rats and Guinea-Pigs in Plague "Barometers". PMID- 29004929 TI - Snakebite, Case. PMID- 29004931 TI - Treatment of Otorrhoea. PMID- 29004932 TI - Case of Hyperpyrexia. PMID- 29004933 TI - Quackery in India. PMID- 29004934 TI - Snakebite, Case. PMID- 29004936 TI - Preliminary Note on Quinine Sulphate as a Factor in the Causation of BlackWater Fever. PMID- 29004935 TI - Extra-Peritoneal Wound of Intestines. PMID- 29004937 TI - Relapsing Fever, an Outbreak. PMID- 29004939 TI - Abscesses of Liver: Recovery. PMID- 29004938 TI - Horse-Shoe Kidney. PMID- 29004940 TI - Weight of Calculi. PMID- 29004941 TI - Malaria in Pregnancy. PMID- 29004943 TI - Cyllin and Rideal-Walker Co-Efficient. PMID- 29004942 TI - Sixty-One Eye Operations in One Day. PMID- 29004945 TI - Rideal-Walker Co-Efficients of the Following Disinfectants (On Bacillus Typhosus). PMID- 29004944 TI - Malta Fever in India. PMID- 29004946 TI - Therapeutic Notes and Preparations: 'Tabloid' 'Gingamint' (Soda Mint Compound). PMID- 29004947 TI - Rupture of Uterus. PMID- 29004949 TI - Injuries and Tetanus. PMID- 29004948 TI - Injury of Thoracic Duet. PMID- 29004951 TI - Doctors' Fees for Cancelled Engagements. PMID- 29004950 TI - Supply of Vaccines and Serums in India. PMID- 29004952 TI - Notes on Current Topics. PMID- 29004953 TI - Medical Society. PMID- 29004954 TI - Catarrhal Jaundice. PMID- 29004956 TI - The Government Regulation of Medical Fees. PMID- 29004955 TI - Quinine in Pregnancy. PMID- 29004957 TI - Notes on 103 Gynaecological Abdominal Sections. PMID- 29004958 TI - Note on the Metabolism of Native Prisoners in the Presidency Jail, Calcutta. PMID- 29004959 TI - Unqualified Practice in India. PMID- 29004960 TI - The Weight of Vesical Calculi. PMID- 29004961 TI - The Work of the Jullundur Civil Hospital in 1906. PMID- 29004963 TI - Privilege Leave and Staff Pay. PMID- 29004962 TI - A Cabinet for Preserving Stools for Examination. PMID- 29004964 TI - Correspondence. PMID- 29004965 TI - Privilege Leave and Staff Pay. PMID- 29004966 TI - Service Notes. PMID- 29004967 TI - Blackwater Fever in Burma. PMID- 29004969 TI - Notes on Current Topics. PMID- 29004968 TI - A Five-Day Fever of Calcutta. PMID- 29004970 TI - The Etiology of Black-Water Fever. PMID- 29004972 TI - The Disposal of Sewage in Cantonments. PMID- 29004971 TI - History of the Indian Medical Service. PMID- 29004973 TI - The United Services Medical Society. PMID- 29004974 TI - The Radical Treatment of Hydrocele. PMID- 29004975 TI - Liq. Sodae Chlorinatae as a Dressing. PMID- 29004976 TI - The Radical Treatment of Hydrocele. PMID- 29004977 TI - On the Incidence of Small-Pox in Calcutta. PMID- 29004978 TI - The Radical Treatment of Hydrocele. PMID- 29004979 TI - The Treatment of Dysentery. PMID- 29004980 TI - History of the Indian Medical Service. PMID- 29004981 TI - The Use of Quinine in Pregnancy. PMID- 29004983 TI - Therapeutic Notes and Preparations. PMID- 29004982 TI - The Flea-Killing Power of Various Chemicals. PMID- 29004984 TI - Notes on Current Topics. PMID- 29004985 TI - The Radical Treatment of Hydrocele. PMID- 29004986 TI - Sir Joseph Fayrer. PMID- 29004987 TI - A Plea for Scraps: "All Knowledge Is Scrappy."-Berthelot. PMID- 29004988 TI - Service Notes. PMID- 29004989 TI - Medicolegal. PMID- 29004990 TI - Stones in the Urethra. PMID- 29004991 TI - Two Unusual Post-Mortems. PMID- 29004992 TI - An Outbreak of Trichinosis in Garhwal: Translation of a Report, Dated 27th March 1907, From Harak Singh, Patwari, of Talla Painkhanda. PMID- 29004993 TI - The New Antiplague Campaign. PMID- 29004994 TI - Doctor's Fees for Cancelled Engagements. PMID- 29004995 TI - Further Experiments as to the Potency to Various Disinfectants against Pulex Cheopis. PMID- 29004996 TI - A Case of Faciolopsis Buski: (Distoma Buski v. Crassum) and Amphistoma Hominis. PMID- 29004997 TI - A Case of an Abscess of Liver Recovery. PMID- 29004998 TI - The Rideal-Walker Co-Efficient. PMID- 29005000 TI - Notes on Current Topics. PMID- 29004999 TI - Case of Old Standing Dysentery Treated by Vaccino-Therapy: As Recommended by Capt. Forster, I.M.S., I. M. G., June 1907. PMID- 29005001 TI - Incinerators in Cantonments. PMID- 29005003 TI - Medical Cases. PMID- 29005002 TI - Fracture of the Skull. PMID- 29005005 TI - Therapeutic Notes and Preparations. PMID- 29005004 TI - An Iodide Eruption. PMID- 29005006 TI - The "Breeding Season" of Rats and the Epidemiology of Plague in Calcutta. PMID- 29005007 TI - Fever Associated with Spirochaetes in the Blood. PMID- 29005008 TI - The Urine and Blood of Europeans and Bengalis. PMID- 29005009 TI - Occupation for Retired Officers. PMID- 29005010 TI - Another Special Plague Number. PMID- 29005011 TI - Service Notes. PMID- 29005012 TI - Cats as Plague Preventers: A Report on the Cat Census in the Amraoti District. PMID- 29005013 TI - Melanotic Sarcoma and "Sarcomatous Melanoma". PMID- 29005014 TI - The Hypodermic Use of Quinine. PMID- 29005016 TI - The Opsonic Index and Its Utility. PMID- 29005015 TI - Blackwater Fever: The Liverpool School's Views. PMID- 29005017 TI - Kala-Azar in the United Provinces. PMID- 29005018 TI - Privilege Leave and Staff Pay. PMID- 29005019 TI - An Operation for Entropion. PMID- 29005020 TI - Service Notes. PMID- 29005022 TI - History of the Indian Medical Service. PMID- 29005021 TI - Preliminary Note on the Application of Vaccino-Therapy to Dysentery. PMID- 29005024 TI - Therapeutic Notes and Preparations. PMID- 29005023 TI - The Report of the Medical College Hospital, Calcutta. PMID- 29005026 TI - Notes on Current Topics. PMID- 29005025 TI - The Use of Small Incinerators. PMID- 29005027 TI - Two Surgical Cases. PMID- 29005028 TI - Late Teething in India. PMID- 29005029 TI - Rat Poisoning and Its Effects in Azamgarh City. PMID- 29005030 TI - Small Incinerators. PMID- 29005031 TI - Pratt's Operation for Hydrocele. PMID- 29005032 TI - The Varieties of Hydrocele. PMID- 29005033 TI - The Misuse of the Term "Rheumatism". PMID- 29005034 TI - A Case of Spinal Injury. PMID- 29005035 TI - Pratt's Operation for Hydrocele. PMID- 29005036 TI - Radical Cure of Hydrocele. PMID- 29005037 TI - Infantile Mortality in India. PMID- 29005038 TI - Service Notes. PMID- 29005040 TI - The Prophylaxis of Plague. PMID- 29005039 TI - Radical Cure of Hydrocele. PMID- 29005041 TI - Notes on Current Topics. PMID- 29005042 TI - Angio-Neurotic OEdema: A Case of This Disease with Some Remarks on Its Pathology. PMID- 29005043 TI - History of the Indian Medical Service. PMID- 29005044 TI - Internal Derangements of the Knee Joint. PMID- 29005045 TI - Malta Fever in Bundelkhand. PMID- 29005046 TI - Short Report on Four Cases of Leishman-Donovan Infection in Gurkhas. PMID- 29005047 TI - Disinfectants against Fleas. PMID- 29005048 TI - A Machine for Loading Vaccine Tubes. PMID- 29005049 TI - A Mahomedan Civilian on Indian Sanitation. PMID- 29005050 TI - The Incidence of Typhoid Fever on Civilian Europeans and on Natives in Calcutta. PMID- 29005051 TI - The B. M. A. Meeting, 1907. PMID- 29005053 TI - The Indian Military Family Pension Fund. PMID- 29005052 TI - The Use of Rubber Gloves in India. PMID- 29005054 TI - Viper Bite, Case of. PMID- 29005055 TI - Hydrocele Operations. PMID- 29005056 TI - What We Know of Elephantiasis. PMID- 29005057 TI - Cellulitis, Case of. PMID- 29005058 TI - Dr. Waller's Address on Anaesthetics. PMID- 29005059 TI - Case of Snake-Bite. PMID- 29005060 TI - Special Senses. PMID- 29005061 TI - New and Old Treatment of Ague Case. PMID- 29005062 TI - Developments in Eye Surgery. PMID- 29005064 TI - Expression of Cataract. PMID- 29005065 TI - Therapeutic Notes and Preparations. PMID- 29005063 TI - Service Notes. PMID- 29005066 TI - Some Forms of Headache. PMID- 29005067 TI - Notes on Current Topics. PMID- 29005068 TI - An Outbreak of Dropsy. PMID- 29005069 TI - Black-Water Fever in Jeypore Agency. PMID- 29005071 TI - Typhoid Ulcer, Perforation. PMID- 29005070 TI - Operations for Hydrocele. PMID- 29005072 TI - Fowl Spirillosis. PMID- 29005074 TI - The Proposed Bengal Hospital for the Insane. PMID- 29005073 TI - Operations for Hydrocele: A Further Communication. PMID- 29005076 TI - The Radical Cure of Hydrocele, by Incision and Eversion of the Sac. PMID- 29005075 TI - Notes of a Successful Ovariotomy. PMID- 29005077 TI - The Hypodermic Use of Quinine. PMID- 29005078 TI - The Bacterial Indicators of Water Pollution. PMID- 29005079 TI - Service Notes. PMID- 29005081 TI - The Hypodermic Use of Quinine. PMID- 29005080 TI - The Cultivation and Preservation of Calf Lymph. PMID- 29005082 TI - A Plea for a More General Use of Desmarre's Eye-Lid Retractor in Cataract Extraction. PMID- 29005083 TI - Abdominal Pain in Pneumonia. PMID- 29005084 TI - Sepsis and Asepsis. PMID- 29005085 TI - Notes on Current Topics. PMID- 29005086 TI - Coloptosis and Its Treatment. PMID- 29005087 TI - A Case of Traumatic Femoral Aneurism. PMID- 29005088 TI - Two Cases of Subcranial Haemorrhage. PMID- 29005089 TI - Arthritis in Dysentery. PMID- 29005090 TI - History of the Indian Medical Service. PMID- 29005092 TI - Notes on the High Rate of Infantile Mortality in Chingleput. PMID- 29005091 TI - Conservancy in Small Towns. PMID- 29005093 TI - Some Hospital Cases. PMID- 29005094 TI - Unusual Cases of Ovarian Cyst. PMID- 29005095 TI - The Hypodermic Use of Quinine. PMID- 29005096 TI - Aneurism of the Common Carotid Artery. PMID- 29005097 TI - Albuminuria and the Duration of Albuminuria in Cholera. PMID- 29005098 TI - Extra-Peritoneal Transplantation of Ureters into the Rectum. PMID- 29005099 TI - Notes on Current Topics. PMID- 29005100 TI - The Hypodermic Use of Quinine. PMID- 29005101 TI - The Hypodermic Use of Quinine. PMID- 29005102 TI - A Case of "Typho-Malarial Fever". PMID- 29005103 TI - Rheumatism: Its Forms, Course, Prevalence, Etiology in Relation to the Peculiar Conditions of the Soil and Climate, and Treatment Adopted, Being a Short Resume of 976 Cases Treated (1897-1906) at the Northern India Salt Revenue Hospital. And Jodhpur Raj Dispensary at Bhatki Sanchor Luni Salt Sources, Marwar. PMID- 29005104 TI - The Operation of Transplantation of the Cornea. PMID- 29005105 TI - The Burma Government Medical School. PMID- 29005106 TI - The Hypodermic Use of Quinine. PMID- 29005107 TI - Visit to Surgical Clinic of the Drs. Mayo at Rochester, U. S. A. PMID- 29005109 TI - The Manual of Aseptic Surgery. PMID- 29005108 TI - Cerebro-Spinal Meningitis. PMID- 29005111 TI - Service Notes. PMID- 29005110 TI - Therapeutic Notes and Preparations. PMID- 29005112 TI - Civil Hospital Assistants. PMID- 29005114 TI - Lotio Liquor Sodae Chlorinatae. An Excellent Dressing. PMID- 29005113 TI - "Small" Incinerators. PMID- 29005115 TI - Note on the Occurrence of Amoeba Coli in Port Blair, Andaman Islands. PMID- 29005117 TI - Therapeutic Notes and Preparations. PMID- 29005116 TI - Recent Advances of Knowledge in Connection with Rabies. PMID- 29005118 TI - A Fatal Case of Snake Poisoning. PMID- 29005119 TI - Visit to the Augustana Hospital, Chicago, U. S. A. PMID- 29005120 TI - The Plague in Kashmir. PMID- 29005121 TI - Case of Sarcoma of the Temporal Fascia. PMID- 29005122 TI - Cerebro-Spinal Meningitis in Bhagalpur in 1906. PMID- 29005123 TI - History of the Indian Medical Service. PMID- 29005125 TI - Indian Birth-Rates. PMID- 29005124 TI - A Case of Transverse Fracture of the Patella. Fragments Wired by the Open Method. PMID- 29005126 TI - Malta Fever in the Punjab. PMID- 29005128 TI - Notes on Current Topics. PMID- 29005127 TI - The Value of Creasote Inunction in Medicine. PMID- 29005129 TI - Medical Society. PMID- 29005130 TI - Malarial Pneumonia. Is There Such a Thing? PMID- 29005131 TI - A Note on Two Native Remedies for Acute Dysentery. PMID- 29005133 TI - Service Notes. PMID- 29005132 TI - Two Unusual Cases of the Presence of Ascaris Lumbricoides. PMID- 29005135 TI - Therapeutic Notes and Preparations. PMID- 29005134 TI - An Abnormal Origin of the Pectoralis Major. PMID- 29005137 TI - The I. M. S. and the Army List. PMID- 29005136 TI - Rectal Injections of Fresh Bile in Tropical Dysentery. PMID- 29005138 TI - Service Notes. PMID- 29005139 TI - An Epidemic of Malignant Jaundice in Bombay. PMID- 29005140 TI - Note on a Possible Case of Malta Fever. PMID- 29005141 TI - Operations for Extirpation of the Spleen. PMID- 29005143 TI - Leishman-Donovan Infection in a Gurkha. PMID- 29005142 TI - Hepatic Abscess, and Some Points in the Diagnosis of Multiple Hepatic Abscess. PMID- 29005144 TI - A Case of Extra-Uterine Pregnancy. PMID- 29005145 TI - An Experimental Investigation as to the Potency of Various Disinfectants against Rat-Fleas. PMID- 29005146 TI - William Hamilton and the Embassy to Delhi. PMID- 29005147 TI - The Hypodermic Use of Quinine. PMID- 29005148 TI - The Grievances of Hospital Assistants. PMID- 29005150 TI - Netley. PMID- 29005149 TI - Corrigendum. AB - [This corrects the article on p. 475 in vol. 41.]. PMID- 29005151 TI - Notes on Current Topics. PMID- 29005152 TI - What Is Saturated Steam. PMID- 29005153 TI - A Year's Experience of Malaria at the Out-Door Department of the Medical College Hospital, Calcutta. PMID- 29005154 TI - Annus Medicus, 1906. PMID- 29005155 TI - Service Notes. PMID- 29005156 TI - A Case of Retained Placenta. Expectant Method of Treatment. PMID- 29005158 TI - Current Topics. PMID- 29005157 TI - Gleanings from the Calcutta Post-Mortem Records : II.-The Incidence of Tuberculous Diseases in Bengal. PMID- 29005159 TI - Motor Cars for Medical Men in India. PMID- 29005160 TI - A Case of Prostatectomy at the Dhubri Hospital. PMID- 29005161 TI - Some Cases of Intestinal Obstruction. PMID- 29005162 TI - Malarial Prophylaxis. PMID- 29005163 TI - Quinine and Pregnancy. PMID- 29005164 TI - The Biliary Cirrhosis of Children: Otherwise Known as Infantile Liver. PMID- 29005165 TI - Spinal Analgesia. PMID- 29005166 TI - Quinine and Pregnancy. PMID- 29005167 TI - Tubercular Diseases in India. PMID- 29005168 TI - Ozone as a Water Purifying Agent in India. PMID- 29005169 TI - Medical Societies. PMID- 29005171 TI - Puerperal Eclampsia. PMID- 29005170 TI - Hydatid Cyst Growing from Vertebral Column. PMID- 29005172 TI - Rupture of the Choroid with Traumatic Mydriasis. PMID- 29005174 TI - Sick Passengers on Steamships. PMID- 29005175 TI - Enormous Ovarian Cyst. PMID- 29005173 TI - Eight Cases of Prostatectomy. PMID- 29005177 TI - Widows' and Families' Pensions. PMID- 29005176 TI - Quinine and Pregnancy. PMID- 29005179 TI - Motoring Notes. PMID- 29005178 TI - Practical Notes on Gloves for Surgical Use. PMID- 29005181 TI - Service Notes. PMID- 29005180 TI - Notes on Two Cases of Excision of the Rectum for Carcinoma. PMID- 29005182 TI - The New Indian Medical Service. PMID- 29005183 TI - Blackwater Fever, Haemolysis and Quinine. PMID- 29005184 TI - A Suggestion for the Treatment of Gonorrhoea. PMID- 29005186 TI - Lycetol and Gout. PMID- 29005185 TI - Pneumonia: Its Treatment by Iron. PMID- 29005187 TI - Malarial Urticaria. PMID- 29005189 TI - On Some Old Eighteenth Century Lists of the I. M. S.: I.-Bengal. PMID- 29005188 TI - Notes on Two Unusual Sequelae of Plague. PMID- 29005191 TI - Special Report of the Medical College Hospital for 1908. PMID- 29005190 TI - The Causation of Sex. PMID- 29005192 TI - The Far Eastern Association of Tropical Medicine. PMID- 29005194 TI - Current Topics. PMID- 29005193 TI - The Sero-Diagnosis of Syphilis. PMID- 29005196 TI - The Medical Section and Tuberculosis. PMID- 29005195 TI - A Case of Pneumococcic Peritonitis. PMID- 29005197 TI - A Note on the Epidemiology of Pneumonic Plague. PMID- 29005198 TI - Service Notes. PMID- 29005200 TI - Current Topics. PMID- 29005199 TI - A Few Notes in Support of Captain Megaw's Article "Are Seven-Day Fever and Three Day Fever Forms of Dengue?" PMID- 29005201 TI - Quinine in Pregnancy. PMID- 29005202 TI - Supersensitiveness to Serum-Injections. PMID- 29005203 TI - A Case of Volkman's Ischemic Paralysis of Both Forearms. PMID- 29005204 TI - Quinine in Pregnancy. PMID- 29005205 TI - Hazaribagh and Tubercular Diseases. PMID- 29005206 TI - Some Remarks on the Prevalence of Tuberculosis among Our Community. PMID- 29005208 TI - Recent Research on the Heart's Action. PMID- 29005207 TI - Tuberculosis Amongst Europeans in Calcutta. PMID- 29005209 TI - Note on Darjeeling Climate in the Treatment of Phthisis. PMID- 29005210 TI - Quackery in India. PMID- 29005211 TI - The Incidence of Phthisis in Calcutta. PMID- 29005212 TI - Determination of Age in the Living. PMID- 29005214 TI - Prostatectomy. PMID- 29005215 TI - Intestinal Animal Parasites in Monghyr. PMID- 29005213 TI - Hazaribagh in Relation to Tubercular Disease and Its Treatment. PMID- 29005216 TI - A Case of Encysted Stone in the Urethral Passage. PMID- 29005217 TI - A Case of Dermoid Cyst. PMID- 29005218 TI - Pyorrhoea Alveolaris. PMID- 29005219 TI - Current Topics. PMID- 29005220 TI - A Case of Atropine Poisoning. PMID- 29005222 TI - Sick Passengers on Liners. PMID- 29005221 TI - The Medical Congress at Bombay. PMID- 29005224 TI - Therapeutic Notes and Preparations. PMID- 29005223 TI - Post-Malarial Ascites. PMID- 29005226 TI - Service Notes. PMID- 29005225 TI - The Treatment of Hydrocele. PMID- 29005227 TI - Indian Medical Congress, Bombay. PMID- 29005229 TI - Tropical Examinations. PMID- 29005228 TI - Spinal Analgesia. PMID- 29005231 TI - Are "Seven-Day Fever" and "Three-Day Fever" Forms of Dengue? PMID- 29005230 TI - Annus Medicus, 1908. PMID- 29005232 TI - John Woodall, Surgeon-General. PMID- 29005233 TI - Dengue and Seven-Day Fever. PMID- 29005234 TI - Phagadenic Ulcers. PMID- 29005235 TI - Phagadenic Ulcers. PMID- 29005236 TI - The Legend of Gabriel Boughton. PMID- 29005237 TI - Quinine and Pregnancy. PMID- 29005238 TI - The Etiology of Beri-Beri. PMID- 29005239 TI - The Inoculation Accident in Manila, P. I., in 1906. PMID- 29005240 TI - A Case of Myxoma. PMID- 29005241 TI - Quinine in Pregnancy. PMID- 29005242 TI - The I. Subordinate M. Dept., and British Qualifications. PMID- 29005243 TI - A Case of Acute Ascending (Landry's) Paralysis. PMID- 29005245 TI - Haemaglobinuria in Malarial Fever. PMID- 29005244 TI - A Case of Blackwater Fever. PMID- 29005246 TI - Two Cases of Streptococcal Infection. PMID- 29005248 TI - Service Notes. PMID- 29005247 TI - Splenic Anaemia (Banti's Disease). PMID- 29005250 TI - Observations on Spinal Analgesia. PMID- 29005249 TI - Puerperal Eclampsia. PMID- 29005251 TI - Ascites and Pregnancy. PMID- 29005253 TI - Current Topics. PMID- 29005252 TI - Auto-Intoxication and the Lactic Acid Bacillus. PMID- 29005254 TI - Notes on the Preparation, Assistance, After-Treatment and Management of Cataract Cases. PMID- 29005255 TI - A Case of Pancreatic Cyst Treated by Drainage. PMID- 29005256 TI - A Case of Traumatic Aneurismal Varix. PMID- 29005257 TI - Note on Two Cases of Chronic Dysentery, Treated with Forster's Anti-Dysenteric Vaccine. PMID- 29005258 TI - An Exceptional Case of Urticaria. PMID- 29005259 TI - Pensions: Widows and Orphans. PMID- 29005261 TI - Dengue and Chitral Fever. PMID- 29005260 TI - Wanted. PMID- 29005262 TI - Accidental Inoculation with the Virus of Plague. PMID- 29005264 TI - Puerperal Eclampsia. PMID- 29005263 TI - A Use for the Cupping-Glass. PMID- 29005265 TI - The Sickness in the Russo-Japanese War. PMID- 29005266 TI - The Occurrence of Accessory Lobules of the Spigelian Lobe of the Liver. PMID- 29005267 TI - Antiseptic Surgery in Frontier Warfare. PMID- 29005268 TI - Some Motor Cycles at the Stanley Show. PMID- 29005269 TI - Katatonia in India. PMID- 29005271 TI - Current Topics. PMID- 29005270 TI - Service Notes. PMID- 29005273 TI - The Sanatorium Treatment of Tuberculosis. PMID- 29005272 TI - A Round Celled Sarcoma. PMID- 29005274 TI - The Date of Service for Pension Grievance. PMID- 29005276 TI - Supplement to the Indian Medical Gazette, March, 1909. PMID- 29005275 TI - An Outbreak of Mumps. PMID- 29005277 TI - Tubercle of the Lungs in Bengal Jails. PMID- 29005278 TI - A Year's Abdominal Surgery. PMID- 29005280 TI - Bites of the Echis Carinata. PMID- 29005282 TI - Service Notes. PMID- 29005281 TI - Medical Research in India. PMID- 29005284 TI - What the Indian Medical Service Has Done for India. PMID- 29005283 TI - Case of Caecum & Appendix in Left Inguinal Hernia. PMID- 29005286 TI - Sanitary Measures Taken during the Year 1911-12 in India. PMID- 29005285 TI - The Intra-Capsular Operation for Cataract (Smith's Method) from the Point-Of-View of the Civil Surgeon. PMID- 29005287 TI - The Psycho-Analytic Method of Treatment of the Neuroses. PMID- 29005289 TI - Medical Colleges, Schools and Hospitals in India. PMID- 29005288 TI - Review of a Year's Medico-Legal Work in the Calcutta Morgue, 1911. PMID- 29005290 TI - Ten Months' Work in Military Employ. PMID- 29005291 TI - The Medical Services in 1911. PMID- 29005292 TI - Our Special I. M. S. Number. PMID- 29005293 TI - The Treatment of Guinea-Worm. PMID- 29005294 TI - The Treatment of Aural Sepsis. PMID- 29005296 TI - Service Notes. PMID- 29005295 TI - A Radical Cure of Hydrocele. PMID- 29005298 TI - Foreign Body in the Throat. PMID- 29005297 TI - Hypnotism and Psychotherapy. PMID- 29005299 TI - Syphilis in Tibet. PMID- 29005300 TI - The Bombay Medical Act. PMID- 29005301 TI - Intestinal Parasites in the Wardha District. PMID- 29005302 TI - Appointment to the Service Examination. PMID- 29005303 TI - Sanitation in the Plains. PMID- 29005304 TI - 126 Stones in the Bladder. PMID- 29005305 TI - Current Topics. PMID- 29005307 TI - Air Movement in Association Wards. PMID- 29005306 TI - Sanitation at the Volunteers' Camp, Delhi. PMID- 29005308 TI - Some Notes on the Proposed Bill to Consolidate and Amend the Law Relating to Lunacy. PMID- 29005309 TI - Bicentenary of the School of Physic of Ireland: June, 1912. PMID- 29005310 TI - American Degrees and Diplomas. PMID- 29005311 TI - Design for the Out-Patients Department of a Small Indial Hospital. PMID- 29005312 TI - Some Interesting Cases. PMID- 29005313 TI - The Vaccine Treatment of Pneumonia. PMID- 29005315 TI - Treatment of Small-Pox by Tincture of Iodine. PMID- 29005314 TI - Opium Cures: "Combretum Sundaicum" and "Antipav". PMID- 29005316 TI - A Case for Diagnosis. PMID- 29005317 TI - Rupture of the Spleen: Operation: Recovery. PMID- 29005318 TI - A Change of Title. PMID- 29005319 TI - A Cholera Season: Some Observations, Methods and Results. PMID- 29005320 TI - Details of Vision of 132 Cases of Intracapsular Extraction of Cataract. PMID- 29005321 TI - Inoculation and the Prevalence of Enteric and Paratyphoid Fevers in the European Army. PMID- 29005322 TI - Neo-Salvarsan. PMID- 29005323 TI - Service Notes. PMID- 29005326 TI - Current Topics. PMID- 29005325 TI - Etiology of Deficiency Diseases. PMID- 29005327 TI - The Treatment of Uterine Prolapse. PMID- 29005324 TI - An Outbreak of Urticaria Epidemica. PMID- 29005329 TI - A Case for Diagnosis. PMID- 29005328 TI - The Cinchona Alkaloids. PMID- 29005330 TI - On Some New Anophelines of Calcutta. PMID- 29005331 TI - Current Topics. PMID- 29005332 TI - Vital Statistics. PMID- 29005333 TI - Cowdung and Domestic Hygiene. PMID- 29005334 TI - Service Notes. PMID- 29005335 TI - Lamblia Intestinalis and Poona Diarrhoea. PMID- 29005336 TI - Notes on Early Tubercular Disease of the Calcium. PMID- 29005337 TI - The Value of Polyvalent Serum. PMID- 29005338 TI - The Ganja Habit. PMID- 29005340 TI - Surgical Work at the Prince of Wales' Hospital, Calcutta. PMID- 29005339 TI - Surgical Cases. PMID- 29005342 TI - Medical Service in Campaigns. PMID- 29005341 TI - Service Notes. PMID- 29005343 TI - Service Notes. PMID- 29005344 TI - A Case of Multiple Cysticercus Cellulosae. PMID- 29005345 TI - A Provident Fund. PMID- 29005346 TI - The Treatment of Sprains, Strains, etc., by Movement and Rubbing. PMID- 29005347 TI - Cholera in the Campbell Hospital, 1911. PMID- 29005348 TI - Treatment of Gallstones. PMID- 29005350 TI - New Medical Journals. PMID- 29005349 TI - A Case of Suppurating Ovarian Dermoid Cyst. PMID- 29005352 TI - Intestinal Parasites in the Wardha District. PMID- 29005351 TI - Black-Water Fever in Burma. PMID- 29005353 TI - Correspondence. PMID- 29005354 TI - Cure of Hydrocele by Lymphangioplasty. (Internal Drainage). PMID- 29005355 TI - Ankylostome Infection. PMID- 29005356 TI - A New Method of Intraperitoneal Administration of Rogers' Hypertonic Solution in Cholera. PMID- 29005358 TI - Current Topics. PMID- 29005357 TI - The Treatment of the Early Stages of Senile Cataract. PMID- 29005360 TI - History of a Case of Myositis Ossificans. PMID- 29005359 TI - The Specific Gravity of the Blood and Its Value in the Treatment of Cholera. PMID- 29005361 TI - Treatment of Aural Sepsis. PMID- 29005363 TI - Service Notes. PMID- 29005362 TI - The Need for Conferences among Medical Officers. PMID- 29005364 TI - The Prevention of Guinea-Worm Disease. PMID- 29005366 TI - Filariasis and Elephantiasis. PMID- 29005365 TI - Haschisch. PMID- 29005368 TI - The New Sanitary Scheme for India. PMID- 29005367 TI - Cinchona Plantations in Bengal. PMID- 29005369 TI - Intestinal Parasites in Lower Burma. PMID- 29005370 TI - Treatment of Trachoma. PMID- 29005371 TI - Medical Society. PMID- 29005372 TI - Current Topics. PMID- 29005373 TI - The Use of Ultra-Violet Rays in the Sterilization of Water. PMID- 29005374 TI - A Hitherto Undescribed Infective Disease in Rangoon. PMID- 29005375 TI - Early Tuberculosis. PMID- 29005376 TI - The Outbreak of Rat-Plague in Suffolk and the Manchurian Epidemic of Human Plague. PMID- 29005377 TI - Case of Lymphadenoma. PMID- 29005378 TI - The Tuberculin Method of Treatment. PMID- 29005379 TI - Death from Round Worms in the Throat. PMID- 29005380 TI - An Outbreak of Epidemic Jaundice. PMID- 29005381 TI - Second Clinical Report on the Treatment of Leprosy. PMID- 29005382 TI - Vital Statistics. PMID- 29005383 TI - A Note on Platynemia of the Tibia. PMID- 29005384 TI - The Diameter of the Cornea: Especially in Its Bearing on Cataract Extraction. PMID- 29005385 TI - Case Diagnosed Acute Anterior Poliomyelitis. PMID- 29005386 TI - Extermination of Vermin-Solution D. PMID- 29005388 TI - Martindale's Special Preparations. PMID- 29005387 TI - Physaloptera Larvae in the Peritoneum. PMID- 29005390 TI - A New Coating for Pills. PMID- 29005389 TI - Query. PMID- 29005391 TI - Action of White Santonin in Night-Blindness Due to Intestinal Worms. PMID- 29005392 TI - The Acidosis Index. PMID- 29005393 TI - Therapeutic Use of Tuberculin in Tuberculosis. PMID- 29005394 TI - The Voluntary Boarder. PMID- 29005396 TI - Sixty Cases of Amoebic Dysentery Illustrating the Treatment by Ipecacuanha and Emetine Respectively. PMID- 29005395 TI - Some Notes of an Epidemic of Dengue Form Fever Amongst Indian Troops, Calcutta. PMID- 29005397 TI - Regulin. PMID- 29005399 TI - Dengue Fever. PMID- 29005398 TI - Emetine and Tropical Diarrhoea. PMID- 29005400 TI - The Bacteriological Department. PMID- 29005401 TI - Infantile Beri-Beri. PMID- 29005402 TI - A Developmental Defect. PMID- 29005403 TI - Treatment of Small-Pox by Tincture of Iodine. PMID- 29005405 TI - Service Notes. PMID- 29005404 TI - Correction. AB - [This corrects the article on p. 296 in vol. 47.]. PMID- 29005406 TI - Some Interesting Effects of Bromural in a Case of Advanced Diabetes. PMID- 29005407 TI - Current Topics. PMID- 29005408 TI - Sanitary Reorganisation in Bengal. PMID- 29005410 TI - Smith's Operation. PMID- 29005409 TI - A Case of Multiple Hydatid. Infection of the Abdominal Viscera. PMID- 29005412 TI - Bombay Medical Bill. PMID- 29005411 TI - Prostatectomy. PMID- 29005413 TI - A Case of Acute Polioencephalitis Superior: With Amentia: Recovery. PMID- 29005415 TI - Note on Complement Deviation in the Sera of Vaccinated Calves. PMID- 29005414 TI - A Case of Infantile Umbilical Hernia. PMID- 29005416 TI - The Treatment of Trachoma. PMID- 29005418 TI - The Treatment of Oriental Sore by CO2 Snow. PMID- 29005417 TI - A Note on Some Cases of Probable Lathyrism. PMID- 29005419 TI - Convict Marriages in the Andamans. PMID- 29005421 TI - Medical Societies. PMID- 29005420 TI - Food and Drugs Act in India. PMID- 29005422 TI - Literary Notes. PMID- 29005423 TI - Service Notes. PMID- 29005424 TI - A Case of Tetanus Infection from an Operation Wound. PMID- 29005425 TI - Gleanings from the Calcutta Post-Mortem Records : No. V.-Diseases of the Lung Other Than Tubercle. PMID- 29005426 TI - Current Topics. PMID- 29005427 TI - Treatment of Trachomatous Conditions by Sub-Conjunctival Injections of Cyanide of Mercury. PMID- 29005428 TI - The King George's Medical School College, Lucknow. PMID- 29005429 TI - Observations on Three Hundred Cases of Guinea-Worm. PMID- 29005430 TI - Nastin Treatment of Leprosy. PMID- 29005431 TI - Popular Prejudices about Malaria and Quinine. PMID- 29005432 TI - Current Topics. PMID- 29005433 TI - Insanity in the Andamans. PMID- 29005435 TI - Formalin as a Poison for Flies. PMID- 29005434 TI - Cases of Hydatid Cyst. PMID- 29005436 TI - Rice as a Food. PMID- 29005437 TI - Mongolian Birth Marks. An Anthropological Study. PMID- 29005438 TI - Transfusion of Blood in 15th Century. PMID- 29005439 TI - Service Notes. PMID- 29005440 TI - Large Renal Calculus. PMID- 29005441 TI - A Peculiar Fever Met with on the N.-W. Frontier. PMID- 29005442 TI - The Asylum Question in India. PMID- 29005443 TI - Multiple Hydatidose Echinococcal Infection of the Abdominal Viscera. PMID- 29005445 TI - Melon Eating and Choleraic Attacks. PMID- 29005444 TI - Hypodermic Syringe. PMID- 29005446 TI - Covering. PMID- 29005447 TI - Indian Medical Service in 1911. PMID- 29005448 TI - Air in the Bladder Amongst Women. PMID- 29005449 TI - The Research Defence Society and Anti-Vivisection Shops. PMID- 29005451 TI - Current Topics. PMID- 29005450 TI - Some Fractures Treated by Operations. PMID- 29005452 TI - Appointment to the Service Examination. PMID- 29005453 TI - Tetanus and Quinine. PMID- 29005454 TI - Abor Arrow Poison. PMID- 29005455 TI - Antistreptococcus Serum in Erysipelas. PMID- 29005456 TI - Annus Medicus (1911). PMID- 29005457 TI - An Improved Method of Using the Tonsil Guillotine. PMID- 29005458 TI - Presidential Address. PMID- 29005459 TI - The Bombay Sanitary Conference. PMID- 29005460 TI - Cysticercus Cellulosae. PMID- 29005462 TI - Some Notes on the Teaching of Anatomy. PMID- 29005461 TI - Service Notes. PMID- 29005463 TI - Surgical Cases. PMID- 29005464 TI - The Extraction of Cataract in Its Capsule, by Division of the Suspensory Ligament. PMID- 29005465 TI - Bugs and Their Remedy. PMID- 29005466 TI - Hypodermic Syringe. PMID- 29005467 TI - Abscess of Liver with Amoebae, but without Antecedent Bowel Disease. PMID- 29005468 TI - A Fatal Case of Haemorrhage into the Pancreas. PMID- 29005469 TI - 'Wellcome' Brand Streptococcus Vaccine, Dental. PMID- 29005471 TI - An Investigation into the Treatment of Snake-Bite by Permanganate of Potassium. PMID- 29005470 TI - Gleanings from the Calcutta Post-Mortem Records. PMID- 29005473 TI - Prevention of Pernicious Malaria. PMID- 29005474 TI - Protein Element in Nutrition. PMID- 29005472 TI - A Case in Which Von Pirquet's Reaction Was Followed by Ascites. PMID- 29005475 TI - Case of Molluscum Fibrosum with Definite Family History. PMID- 29005476 TI - Service Notes. PMID- 29005478 TI - 'Vaporole' Pituitary Extract 0.5 C.C. PMID- 29005477 TI - Bullet Wound of the Lower End of the Femur. Death from Haemorrhage from the Popliteal Artery Nine Days Later. PMID- 29005480 TI - The Peristaltic Hormone. PMID- 29005479 TI - Current Topics. PMID- 29005481 TI - Notes on a Case of Double Volvulus of the Large Intestines and on One of Posterior Gastro-Jejunostomy. PMID- 29005482 TI - Honours and Rewards. PMID- 29005483 TI - A Special Type of Recurrent Fever Due to a Spirochaeta. PMID- 29005484 TI - The Relationship between "Pyrexia of Uncertain Origin" and Enteric Fever. PMID- 29005485 TI - Convict Marriages. PMID- 29005486 TI - Glycerin as an Antiphlogistic. PMID- 29005488 TI - Formalin against Flies. PMID- 29005487 TI - Case of Abdominal Plague. PMID- 29005489 TI - Presidential Address, Delivered at the Third Meeting of the General Malaria Committee Held at Madras on the 18th November 1912. PMID- 29005490 TI - Current Topics. PMID- 29005491 TI - Eclampsia and the Monsoon. PMID- 29005493 TI - A Query. PMID- 29005492 TI - Poisoning by Cassia Occidentalis. PMID- 29005494 TI - Late Dr. Busteed, I.M.S. PMID- 29005495 TI - Popularity of I. M. S. PMID- 29005496 TI - Spirillar Fever in Darjeeling. PMID- 29005497 TI - Case of Cerebro-Spinal Fever. PMID- 29005499 TI - Service Notes. PMID- 29005498 TI - Radio-Activity. PMID- 29005500 TI - White Men in the Tropics. PMID- 29005501 TI - Case of Enteric Fever. PMID- 29005502 TI - Sir R. Ross and I.M.S. PMID- 29005503 TI - Infelix Opportunitate. PMID- 29005504 TI - Permanganate and Snake-Bite: A Reply. PMID- 29005505 TI - Case of Conservative Surgery. PMID- 29005506 TI - Sandfly Fever. PMID- 29005507 TI - Surgery at Poona. PMID- 29005508 TI - Medical Societies. PMID- 29005510 TI - A Case of Rupture of Uterus in an Old Caesarean Section Scar. PMID- 29005509 TI - Ascites and Cirrhosis. PMID- 29005511 TI - Osteomalacic Pelvis, Full Term Pregnancy. Porro's Operation. PMID- 29005512 TI - Indian Military Family Pension Fund. PMID- 29005514 TI - Current Topics. PMID- 29005513 TI - Service Notes. PMID- 29005516 TI - The Intravenous Administration of Salvarsan. PMID- 29005515 TI - Night-Soil Conservancy in Cantonments. PMID- 29005517 TI - Lipo-Fibroma of the Tonsil. PMID- 29005519 TI - Indian Military Family Pension Fund. PMID- 29005518 TI - Bugs in Railway Carriages. PMID- 29005520 TI - Canal Zone Medical Association. PMID- 29005521 TI - Notes on an Epidemic of Pyrexia of Uncertain Origin. PMID- 29005522 TI - A Case of Sub-Conjunctival Cysticercus Cellulosae. PMID- 29005523 TI - Apparatus for the Treatment of Cholera by Hypertonic Saline Infusion. PMID- 29005524 TI - Multiple Cysticercus Cellulosae of the Brain. PMID- 29005525 TI - Intracapsular Removal of Cataract: Experiences and Suggestions. PMID- 29005527 TI - Current Topics. PMID- 29005526 TI - Drugs and Drug Habits in Burma. PMID- 29005528 TI - Correspondence. PMID- 29005529 TI - A Resume of Researches on Endemic Goitre. PMID- 29005530 TI - Averages of Weight and Chest Measurements of 705 Madras Coolies. PMID- 29005531 TI - Service Notes. PMID- 29005532 TI - Organisms in Dysentery Stools. PMID- 29005534 TI - Post-Graduate Study in Europe. PMID- 29005533 TI - Some Observations on Hydrocele. PMID- 29005535 TI - Zoological Nomenclature. PMID- 29005536 TI - The Division of the Suspensory Ligament of the Lens, as a Preliminary to Intra Capsular Extraction of Cataract. PMID- 29005537 TI - The Treatment of Leprosy by the Use of a Vaccine Prepared from Cultivations of the Leprosy Streptothrix. PMID- 29005538 TI - On an Anopheline Allied to Myzomyia Listoni. PMID- 29005540 TI - The Dawn of a Health Age. PMID- 29005539 TI - Ownership of Prescriptions. PMID- 29005541 TI - Operation Theatre with Accommodation for 20 Students. PMID- 29005542 TI - The Lucknow Medical College. PMID- 29005543 TI - A Few Notes about Melbourne and Its Hospitals. PMID- 29005545 TI - Caecum in Left Inguinal Hernia. PMID- 29005544 TI - The Uncovenanted and Subordinate Medical Services. PMID- 29005547 TI - Research Defence Society. PMID- 29005546 TI - The Value of Eucalyptus. PMID- 29005549 TI - Current Topics. PMID- 29005548 TI - Annus Medicus. PMID- 29005550 TI - Arrows and Arrow Wounds in Manbhoom. PMID- 29005551 TI - Service Notes. PMID- 29005552 TI - Sir John McNeill, G C.B. PMID- 29005554 TI - The Health of a Bengal District. PMID- 29005553 TI - Historical Note on Cholera in India. PMID- 29005555 TI - Medical Society. PMID- 29005556 TI - A Case of Traumatic Rupture of the Prostatic Urethra. PMID- 29005558 TI - A Medico-Legal Query. PMID- 29005557 TI - Contents of a Hernial Sac. PMID- 29005559 TI - A Case of General Paralysis of the Insane in a Native of India. PMID- 29005561 TI - The Ipecacuanha Treatment in Liver Abscess. PMID- 29005560 TI - Two Cases of Ascariasis. PMID- 29005562 TI - A Forecast of Medical Matters. PMID- 29005564 TI - Current Topics. PMID- 29005563 TI - Ligature of Carotid Artery. PMID- 29005565 TI - Leucoderma in Burma. PMID- 29005567 TI - The Incidence of Diphtheria in India. PMID- 29005566 TI - A Rational Puerperium. PMID- 29005568 TI - Dilatation of the Anus as a Means of Resuscitation in Chloroform Anaesthesia with Suggestion for Its Use in Cases of Drowning. PMID- 29005569 TI - Rubber Gloves in Modern Midwifery Practice in India. PMID- 29005571 TI - Service Notes. PMID- 29005570 TI - A North-East Frontier Expedition. PMID- 29005572 TI - Laboratory Work in Military Hospitals. PMID- 29005574 TI - Blood Pressure in Natives. PMID- 29005573 TI - Supplement to "The Indian Medical Gazette." May, 1911. PMID- 29005576 TI - Haemateikona. The Significance of the Blood Picture in Disease. PMID- 29005575 TI - Hill Climates. PMID- 29005577 TI - A Case of Tetanus. PMID- 29005578 TI - Military Assistant-Surgeons' Memorial. PMID- 29005579 TI - A Peculiar Pigmentary Condition. PMID- 29005580 TI - Gall-Bladder Affections. PMID- 29005581 TI - A Modern Hospital for the Insane. PMID- 29005582 TI - Air Injection for Sciatica. PMID- 29005584 TI - Military Medical Subordinates. PMID- 29005583 TI - The Plague of Flies. PMID- 29005585 TI - Some Considerations of Medical Education. PMID- 29005587 TI - Current Topics. PMID- 29005586 TI - Gleanings from the Calcutta Post-Mortem Records-IV. Cirrhosis of the Liver. PMID- 29005588 TI - Bugs in Railway Carriages. PMID- 29005589 TI - Treatment of Kala-Azar by the Hypodermic Injection of Quinine. PMID- 29005590 TI - Doctors in Parliament. PMID- 29005591 TI - Service Notes. PMID- 29005592 TI - A Speculation on Diabetes Mellitus: Preliminary Note. PMID- 29005593 TI - On the Technique of Hypodermic Injection. PMID- 29005594 TI - Sand-Fly Fever in Chitral. PMID- 29005595 TI - An Unusual Complication in Lithotomy. PMID- 29005597 TI - Pancreatic Cysts. PMID- 29005596 TI - A Method of Performing Gastro-Jejunostomy. PMID- 29005598 TI - Claud Martin and the Operation for Stone. PMID- 29005599 TI - Remarks on Ascariasis. PMID- 29005600 TI - Rural Insanitation. PMID- 29005602 TI - Cirrhosis of the Liver. PMID- 29005601 TI - Hill Health Resorts in India. PMID- 29005603 TI - Study Leave, Promotion and Ordinary Leave. PMID- 29005604 TI - Wounds Inflicted by Tigers, Panthers and Bears. PMID- 29005605 TI - Liver Abscess, Aspiration and Injection of Quinine. PMID- 29005607 TI - Length of Russel's Viper. PMID- 29005606 TI - Ulcerated and Swollen Gums in the Native Army. PMID- 29005608 TI - Reply. PMID- 29005610 TI - Native Gun-Powder Injuries of the Eye. PMID- 29005609 TI - The Freiburg Eye Clinic. PMID- 29005611 TI - Exploratory Laparotomy in Affections of the Gall-Bladder and Bile-Ducts. PMID- 29005612 TI - Use of Mosquito Nets in Ancient Egypt. PMID- 29005613 TI - Medical Societies. PMID- 29005614 TI - Medico-Legal Value of the Biochemical Test for Blood-Stains. PMID- 29005615 TI - An Aid to the Diagnosis of Poisonous Snakes. PMID- 29005616 TI - Current Topics. PMID- 29005618 TI - Service Notes. PMID- 29005617 TI - Wanted, Back Numbers of "Indian Medical Gazette". PMID- 29005619 TI - Modern Midwifery Practice in India. PMID- 29005620 TI - A Query. PMID- 29005621 TI - A 50-Rupee Operating Theatre. PMID- 29005623 TI - "The Prevention of Malaria." A Review Reviewed. PMID- 29005622 TI - Research Defence Society. PMID- 29005624 TI - Solid Carbon Dioxide: Its Preparation and Indications for Use. PMID- 29005625 TI - The Light for Eye Work. PMID- 29005626 TI - Service Notes. PMID- 29005627 TI - The Medical Services in 1910. PMID- 29005628 TI - The Examination of the Faeces for Ova of Intestinal Parasites. PMID- 29005629 TI - Service Note. PMID- 29005630 TI - More Notes on Jail Dysentery. PMID- 29005631 TI - Three Cases of Pseudo-Muscular Hypertrophy in One Family. PMID- 29005632 TI - Infantile Biliary Cirrhosis. PMID- 29005633 TI - A Case of Tetanus: Treated by Bacelli's Method in Conjunction with Antitetanic Serum. PMID- 29005635 TI - Quinine and Malaria. PMID- 29005634 TI - The Treatment of Oriental Sore. PMID- 29005636 TI - The Use of Bismuth Paste in Chronic Suppurations. PMID- 29005637 TI - Current Topics. PMID- 29005638 TI - Paludism. PMID- 29005639 TI - Malarial Cachexia, and the Value of Arylarsenates in the Treatment. PMID- 29005640 TI - Review of "A Review Reviewed". PMID- 29005641 TI - Notes on Some Interesting Surgical Cases. PMID- 29005642 TI - Current Topics. PMID- 29005643 TI - Notes on Two Unusual Cases of Head Injury. PMID- 29005644 TI - On the Nature of the Epidemic Fever in Lower Bengal Commonly Known as Burdwan Fever. (1854-75). PMID- 29005645 TI - A Case of Puerperal Eclampsia. PMID- 29005646 TI - Dengue-Like Fevers. PMID- 29005647 TI - Quinine without Tetanus. PMID- 29005648 TI - Notes on a Case of Tetanus with Two Severe Relapses at Long Intervals. PMID- 29005649 TI - Civil Sub-Asst. Surgeons' English Qualification Examination. PMID- 29005650 TI - A Case of Tetanus Treated by Chloretone. PMID- 29005651 TI - A Case of Anencephalic Monster. PMID- 29005652 TI - Drug Adulteration in India. PMID- 29005653 TI - Some Comments of the Amrita Bazar Patrika. PMID- 29005654 TI - A Medico-Legal Query. PMID- 29005655 TI - Rural Insanitation in Bengal. PMID- 29005656 TI - A Case of Malignant OEdema. PMID- 29005657 TI - Treatment of Local Sores by Carbon Dioxide Snow. PMID- 29005658 TI - Punjab Anti-Malarial Campaign. PMID- 29005659 TI - The Treatment of Granular Ophthalmia by the Sub-Conjunctival Injection of a Solution of Cyanide of Mercury. PMID- 29005660 TI - Service Notes. PMID- 29005661 TI - The Treatment of Acute Gonorrhoea. PMID- 29005662 TI - Covering Unqualified Work. PMID- 29005663 TI - Leprosy and Nastin. PMID- 29005664 TI - Ascariasis Simulating Appendicitis. PMID- 29005665 TI - Service Notes. PMID- 29005666 TI - A Medical Research Fund for India. PMID- 29005668 TI - A Fracture of Skull. PMID- 29005667 TI - Serpents and Vitality. PMID- 29005669 TI - Puerperal Eclampsia. PMID- 29005670 TI - Case of General Paralysis. PMID- 29005671 TI - Molluscum Fibroma. PMID- 29005672 TI - Current Topics. PMID- 29005673 TI - Molluscum Fibroma. PMID- 29005674 TI - The Suppression of Plague and Malaria. PMID- 29005675 TI - The Andamans: The Prevalence of Malaria and Its Adverse Effect on the Health of the Convicts. PMID- 29005676 TI - Pelvic Suppurations. PMID- 29005677 TI - Subluxation of the Penis. PMID- 29005678 TI - Tetanus and Quinine: A Consideration of the Value to Clinical Medicine of the Recent Memoir by Sir D. Semple upon the Relation of Tetanus to the Injection of Quinine. PMID- 29005679 TI - I. M. S. & Post-Graduate Study. PMID- 29005680 TI - Surgical Cases. PMID- 29005681 TI - Thanatophidia: A Few More Constant Signs for Diagnosing Certain Snakes, and a Hint on Treatment. PMID- 29005682 TI - On the Biology of Black Mycetoma. PMID- 29005683 TI - Hemiplegia with Lesion in the Crus-Cerebri. PMID- 29005684 TI - A Case of Gastro-Enterostomy. PMID- 29005685 TI - Bombay Malaria. PMID- 29005687 TI - The Thermal Springs of India. PMID- 29005686 TI - A Salvarsan Series. PMID- 29005688 TI - Current Topics. PMID- 29005689 TI - A Radical Cure of Hydrocele. PMID- 29005690 TI - Staff Tours and Their Uses. PMID- 29005691 TI - A Simple Means of Administering Salvarsan. PMID- 29005692 TI - A Case of Madura Foot. PMID- 29005693 TI - A Case of Delirious Malaria. PMID- 29005694 TI - Service Notes. PMID- 29005696 TI - A Case of Strangulated Inguinal Hernia. PMID- 29005695 TI - Medical Societies. PMID- 29005697 TI - Kerosene against Bed Bugs. PMID- 29005698 TI - Rural Insanitation. PMID- 29005699 TI - Perforating Wound of the Heart. PMID- 29005701 TI - Current Topics. PMID- 29005700 TI - Service Notes. PMID- 29005702 TI - Radio-Activity of Some Thermal Springs in Bombay. PMID- 29005703 TI - The Health of British Troops in India. PMID- 29005704 TI - Sub-Asst.-Surgeons' Examinations. PMID- 29005705 TI - Worms and Appendicitis. PMID- 29005707 TI - Leech in the Air Passages. PMID- 29005706 TI - Hepatitis and Ipecacuanha. PMID- 29005709 TI - Tetanus and Quinine. PMID- 29005708 TI - The Food and Drugs Act. PMID- 29005710 TI - An Uncommon Fracture of the Skull. PMID- 29005711 TI - Ultramicroscopic Vision. PMID- 29005712 TI - Blood Pressure. PMID- 29005713 TI - Oriental Sore. PMID- 29005715 TI - New Pattern Urinal (For Use in Forts). PMID- 29005714 TI - Medical Societies. PMID- 29005717 TI - Current Topics. PMID- 29005716 TI - On Two Varieties of Relapsing Fever Spirochaetal Infection in India. PMID- 29005718 TI - Review of a Year's Medico-Legal Work in the Calcutta Morgue, 1910. PMID- 29005720 TI - The Personal Factor in Sanitation. PMID- 29005719 TI - Service Notes. PMID- 29005721 TI - Rupture of Uterus with Recovery. PMID- 29005722 TI - Remedy for the Bugs in Railway Carriages. PMID- 29005723 TI - A Simple and Cheap Litholapaxy Evacuator. PMID- 29005724 TI - Primitive Methods in Rice Milling. PMID- 29005725 TI - A Case of Mesenteric Thrombosis. PMID- 29005726 TI - Some Unusual Cases. PMID- 29005728 TI - Snake-Poisoning in the Hills (7,400 Ft.). PMID- 29005727 TI - Queries on Leprosy. PMID- 29005729 TI - Imperial Medical Reform. PMID- 29005731 TI - Caecum and Appendix in Hernia. PMID- 29005730 TI - Review of a Years' Medico-Legal Work in the Calcutta Morgue, 1912: Including Comparative Figures for the Triennium 1910-1912. PMID- 29005732 TI - A Remedy for Prickly Heat. PMID- 29005734 TI - Rheumatism after Rat-Bite. PMID- 29005735 TI - Chronic Epididymitis. PMID- 29005733 TI - Loose Teeth in Pregnancy. PMID- 29005736 TI - A Mild Epidemic of Jaundice. PMID- 29005737 TI - Free Dispensaries for Poor Children. PMID- 29005738 TI - Malarial Gangrene. PMID- 29005739 TI - Excision of the Thyroid. PMID- 29005740 TI - A Morphin Containing Patent Drug. PMID- 29005742 TI - The Pituitary Gland in Labour. PMID- 29005741 TI - Current Topics. PMID- 29005743 TI - Service Notes. PMID- 29005745 TI - The Medical Board of India Office. PMID- 29005744 TI - Agchylostoma Ceylanicum, a New Human Parasite. PMID- 29005747 TI - Mental Derangements in India: A Criticism (Communicated). PMID- 29005746 TI - Spirillar Fever in the Darjeeling District, 1912. PMID- 29005748 TI - Medical Societies. PMID- 29005749 TI - Health of the American Army. PMID- 29005750 TI - Current Topics. PMID- 29005751 TI - Notes on 100 Consecutive Laparotomies Performed for Pyo-Salpinx in the Civil General Hospital, Rangoon. PMID- 29005752 TI - A Note on Judicial Hanging. PMID- 29005753 TI - The Sero-Diagnosis of Syphilis. PMID- 29005754 TI - Service Notes. PMID- 29005755 TI - The Civil Surgeon and the Independent Local Profession of India. PMID- 29005757 TI - Cocoanut Oil as an Insecticide. PMID- 29005756 TI - Smith's Operation. PMID- 29005758 TI - Dengue at Meerut. PMID- 29005759 TI - The Flexner Report on Medical Education. PMID- 29005760 TI - Natives of India in the I.M.S. PMID- 29005761 TI - Blue Patches on Newborn Infants. PMID- 29005762 TI - Can Cholelithiasis Be Successfully Treated without Operation? PMID- 29005763 TI - Medical Societies. PMID- 29005764 TI - Life Assurance in India. PMID- 29005765 TI - The Common Disease of Hill People. PMID- 29005766 TI - Case of Hydrophobia. PMID- 29005767 TI - Salvarsan in Oriental Sore. PMID- 29005768 TI - Dysentery in Raipur Central Jail. PMID- 29005770 TI - Relapsing Fever in Darjeeling District. PMID- 29005769 TI - Dengue in Guzrat. PMID- 29005772 TI - Medical Education in London. PMID- 29005771 TI - Cobra Poisoning Case. PMID- 29005773 TI - Optimism v. Pessimism in I.M.S. PMID- 29005774 TI - Steam Sterilization and the Choice of a Sterilizer. PMID- 29005775 TI - Current Topics. PMID- 29005776 TI - Sinus Cured by Iodine. PMID- 29005777 TI - Ankylostomes in Bengal. PMID- 29005778 TI - Service Notes. PMID- 29005779 TI - Cerebro-Spinal Fever. PMID- 29005780 TI - Canula for Intravenous Injections. PMID- 29005781 TI - The Preparation Jintan. PMID- 29005782 TI - Treatment of Snake Bite. PMID- 29005783 TI - Iodine and Vaccination. PMID- 29005784 TI - Sunday Holidays. PMID- 29005785 TI - Prostatectomy. PMID- 29005786 TI - Absence of Both Upper Extremities. PMID- 29005787 TI - Disease Carriers. PMID- 29005788 TI - Fracture of Spine. PMID- 29005789 TI - Two Cysts. PMID- 29005790 TI - Current Topics. PMID- 29005791 TI - Fracture of Skull. PMID- 29005792 TI - Gluteal Abscess. PMID- 29005793 TI - Renal Case. PMID- 29005794 TI - The Women's Medical Service. PMID- 29005796 TI - Service Notes. PMID- 29005795 TI - Effects of Iodoform. PMID- 29005797 TI - Some Interesting Cases. PMID- 29005798 TI - Typoparatyphoid Vaccine. PMID- 29005799 TI - Case of Snake-Bite. PMID- 29005800 TI - Medical Conference. PMID- 29005801 TI - Malaria and Colour. PMID- 29005802 TI - Local Anaesthesia. PMID- 29005803 TI - Vital Statistics, Gupta. PMID- 29005804 TI - Current Topics. PMID- 29005806 TI - Fry's Report on Malaria in Bengal. PMID- 29005805 TI - An Improved Method for Staining "Negri Bodies". PMID- 29005807 TI - Travelling Dispensaries in United Provinces. PMID- 29005808 TI - The Service during 1912. PMID- 29005810 TI - Service Notes. PMID- 29005809 TI - White Colonies in the Tropics. PMID- 29005811 TI - Quartan Parasites and Kidney Disease. PMID- 29005812 TI - History of I. M. S.: Courts-Martial. PMID- 29005813 TI - Recent Research on Cholera in India. PMID- 29005814 TI - An Efficient Sterilizer for Use in Small Towns. PMID- 29005816 TI - I. M. S. Promotion 30 Years Ago. PMID- 29005815 TI - Professional Examination for Sub-Assistant Surgeons. PMID- 29005817 TI - Pneumonic Plague in Manchuria. PMID- 29005818 TI - Pyorrhoea Alveolaris in Sylhet Jail. PMID- 29005819 TI - Annus Medicus, 1912. PMID- 29005820 TI - The Deficiency Diseases. PMID- 29005821 TI - Current Topics. PMID- 29005822 TI - Arsenic in the Treatment of Kala-Azar. PMID- 29005823 TI - A Case of Ovarian Foetation. PMID- 29005824 TI - Acute Yellow Atrophy of the Liver. PMID- 29005826 TI - The Leave Difficulty. PMID- 29005825 TI - Sanitarium Treatment for Phthisis. PMID- 29005827 TI - A Case of Bagdad Sores. PMID- 29005828 TI - Trichostrongylus Colubriformis (Giles 1892), a Human Parasite. PMID- 29005829 TI - Extraction of the Lens in Its Capsule. PMID- 29005830 TI - The Nastin Treatment of Leprosy. PMID- 29005831 TI - The Sanitary Requirements of a Slaughter-House in India. PMID- 29005832 TI - Control of the Eye in Cataract Operations. PMID- 29005833 TI - Infelix Ager. PMID- 29005835 TI - The Services in 1912. PMID- 29005834 TI - Indian Sanitary Reforms. PMID- 29005836 TI - Service Notes. PMID- 29005837 TI - An Unusual Case of Enteric Fever. PMID- 29005838 TI - A Rough and Ready Field Sterilizer. PMID- 29005839 TI - Hat-Pin in the Duodenum. PMID- 29005840 TI - Emetine and Liver Abscess. PMID- 29005842 TI - The New I. M. S. Warrant. PMID- 29005841 TI - Pyosalpinx. PMID- 29005843 TI - Sterilized Pus for the Treatment of Infectious. PMID- 29005844 TI - The Psychology of the Anus. PMID- 29005845 TI - A Remedy for Prickly Heat. PMID- 29005846 TI - The Madras General Hospital. PMID- 29005847 TI - Current Topics. PMID- 29005848 TI - Datura Poisoning. PMID- 29005849 TI - A Case of Torsion of the Spermatic Cord. PMID- 29005850 TI - Salvarsan on Tea Estates. PMID- 29005851 TI - A Note on the Preparation and Use of Subgallate of Bismuth Gauze. PMID- 29005852 TI - The Calcutta School of Tropical Medicine. PMID- 29005853 TI - A Case of Infantile Convulsions Due to "Ascarides". PMID- 29005854 TI - Gleanings from the Calcutta Post-Mortem Records: No. VII, Diseases of the Nervous System. PMID- 29005855 TI - Some Notes on Surgical Experience in the Turco-Balkan War. PMID- 29005856 TI - A Large Uterine Fibroid. PMID- 29005857 TI - Medical Societies. PMID- 29005858 TI - Some Observations on the Aetiology of the Malaria in Bengal. PMID- 29005859 TI - Service Notes. PMID- 29005860 TI - Review on 422 Cataracts Done by "Smith's Method". PMID- 29005861 TI - A Case of Serum Therapeutics. PMID- 29005862 TI - Canal Zone Medical Association : October 1911 to March 1912. (Vol. IV, Pt. 2.). PMID- 29005863 TI - Some Signs of Typhoid Fever and Its Treatment. PMID- 29005864 TI - A Residual Eruption in Small-Pox. PMID- 29005865 TI - An Answer to the Query under Date November '12. PMID- 29005866 TI - Pneumococcal Peritonitis. PMID- 29005867 TI - Anaphylaxis. PMID- 29005868 TI - Trachoma, a Chapter in Military Medicine. PMID- 29005869 TI - Spinal Analgesia. PMID- 29005870 TI - Service Notes. PMID- 29005871 TI - Appendicitis in a Hernial Sac. PMID- 29005872 TI - Special Promotions in I. M. S. PMID- 29005873 TI - "Flaming" in Prevention of Plague and Kala-Azar. PMID- 29005874 TI - Two Cases Treated Successfully by Psycho-Therapy. PMID- 29005876 TI - Current Topics. PMID- 29005875 TI - Some Malarial Problems in Bengal. PMID- 29005877 TI - Information in Poisoning Cases. PMID- 29005879 TI - The Value of Amorphous Cinchona Alkaloid in Malaria. PMID- 29005878 TI - Abdominal Section. PMID- 29005880 TI - A Case of Perforating Enteric Ulcer of the Ileum. PMID- 29005882 TI - Sub-Assistant-Surgeons. PMID- 29005881 TI - The Puerperium and Its Relation to Puerperal Fever. PMID- 29005883 TI - Heat-Stroke. PMID- 29005884 TI - Some New Methods of Treatment. PMID- 29005885 TI - Civil Surgeons in Bengal and Bihar. PMID- 29005886 TI - Thoraco-Abdominal Injury with Prolapse of the Stomach. PMID- 29005887 TI - Malaria and Mosquitoes in the Kashmir Valley. PMID- 29005888 TI - Medical Societies. PMID- 29005889 TI - Mental Derangements in India. PMID- 29005890 TI - European Doctors in the Mofussal. PMID- 29005891 TI - Dress Regulations, I.M.S. PMID- 29005892 TI - Current Topics. PMID- 29005893 TI - Service Notes. PMID- 29005894 TI - Iodine as an Aid to Aseptic Vaccination. PMID- 29005895 TI - Night-Soil Incineration in Cantonments. PMID- 29005897 TI - The Modern Hospital. PMID- 29005896 TI - Relapsing Fever in Bulandshahr District. PMID- 29005899 TI - Four Indigenous Drugs. PMID- 29005898 TI - Multiple Injuries of the Face and Head. PMID- 29005900 TI - Surgical Cases: A Case of Left Buccal Cancer with Involvement of Superior Maxillar and Grandular Enlargement. Excision of Cheek and Partial Excision of Upper Jaw; Subsequent Removal of Glands. PMID- 29005902 TI - The Amorphous Cinchona Alkaloids. PMID- 29005901 TI - The Incidence of Malaria in the Town of Arambagh. PMID- 29005903 TI - Malaria in the Andamans: Fever with Jaundice Cases. PMID- 29005905 TI - Service Notes. PMID- 29005904 TI - The Serum Diagnosis of Tubercle by Alexin Fixation. PMID- 29005906 TI - Current Topics. PMID- 29005907 TI - Ligation of the Internal Iliac and Ovarian Arteries. PMID- 29005908 TI - The Pure Amorphous Alkaloid (Of Cinchona). PMID- 29005910 TI - On the Radio-Activity of Some Springs in Bombay. PMID- 29005909 TI - Congenital Absence of Left Half of Diaphragm. PMID- 29005911 TI - Faecal Fistula of 12 Months' Duration: The Result of Strangulated Right Inguinal Hernia. PMID- 29005913 TI - Mental Derangement in India: A Reply to a Criticism. PMID- 29005912 TI - Idiosyncrasy to Common Salt. PMID- 29005914 TI - Pitutrin in Parturition. PMID- 29005915 TI - Hints on the Administration of Chloroform. PMID- 29005916 TI - Bounding Bed-Bugs. PMID- 29005917 TI - Typhoid Fever in Travancore. PMID- 29005918 TI - A Quantitative Estimation of Chlorides in the Blood. PMID- 29005919 TI - The Diagnosis and Treatment of Chronic Malaria and Kala-Azar. PMID- 29005920 TI - Medical Societies. PMID- 29005921 TI - Some Unusual Forms of the Parasite of Pernicious Malaria, Found in Blackwater Fever. PMID- 29005922 TI - Report on Cases of Leprosy Treated with Leproline during 1911-12 in the Bilaspur District. PMID- 29005924 TI - Infirmities as Shown by the Census. PMID- 29005923 TI - Sanitary Organisation of Our Army in India in War. PMID- 29005926 TI - Current Topics. PMID- 29005925 TI - Blue Patches on New Born Infants. PMID- 29005927 TI - Overcrowding in Barracks and Tubercular Affections among Gurkhas. PMID- 29005929 TI - Pappataci Fever. PMID- 29005928 TI - Formalin against Flies. PMID- 29005930 TI - The Differential Blood Count in Dengue. PMID- 29005931 TI - The Problem of Dengue, Three-Day and Seven-Day Fever. PMID- 29005932 TI - A Theory of the Relations of the Malarial Plasmodium to Its Alternative Hosts. PMID- 29005934 TI - Service Notes. PMID- 29005933 TI - The Smith Operation. PMID- 29005936 TI - The Last of Our Lucknow Veterans. PMID- 29005937 TI - Tropical Medicine at the Ghent Exhibition. PMID- 29005935 TI - Re Bedbugs and Their Destruction. PMID- 29005938 TI - Is Syphilis a Factor in Blackwater Fever? PMID- 29005939 TI - A Case of Myelocythaemia. PMID- 29005940 TI - A Note in Frontier Sores. PMID- 29005941 TI - Devil Driving. PMID- 29005942 TI - A Surgical Curiosity. PMID- 29005943 TI - Current Topics. PMID- 29005945 TI - Note on the Use of Chionanthus Virginiana in Diseases of the Liver. PMID- 29005944 TI - Delayed Chloroform Poisoning. PMID- 29005946 TI - Case of Snake-Bite. PMID- 29005947 TI - Intestinal Obstruction and Scurvy. PMID- 29005948 TI - A Note on Some Uses of a Modified Purin-Free Diet. PMID- 29005950 TI - Competition for the I. M. S. PMID- 29005949 TI - The Indian Journal of Medical Research. PMID- 29005951 TI - On the Use of Scopolamine, Morphine and Atropine during Chloroform Anaesthesia. PMID- 29005952 TI - Excision of the Thyroid, at the Sree Sree Sree Bir Hospital, Nepal. PMID- 29005953 TI - Relapsing Fever in Chitral. PMID- 29005954 TI - Service Notes. PMID- 29005955 TI - Round Worms and Pregnancy. PMID- 29005956 TI - Dengue. PMID- 29005957 TI - Modern Food Reformers. PMID- 29005959 TI - Editorial Notes on Current Topics. PMID- 29005958 TI - Enlargement of the Prostate in Natives of India. PMID- 29005960 TI - Extraction of Cataract in the Capsule. PMID- 29005961 TI - Medicine. PMID- 29005962 TI - Report on the Prevalence of Yaws in the Lower Chindwin District, Upper Burma. PMID- 29005963 TI - The Treatment of Chronically Enlarged Spleen Cases. PMID- 29005965 TI - A Case of Intestinal Obstruction, Due to a Stone; Operation : Recovery. PMID- 29005964 TI - An Analysis of 50 Consecutive Abdominal Sections for Female Pelvic Disease. PMID- 29005966 TI - Examining for Stone in the Bladder. PMID- 29005967 TI - A Case of Total Extirpation of the Prostate by Freyer's Suprapubic Method. PMID- 29005968 TI - The Anointing of the Bladder in the After-Treatment of Operations for Vesical Calculi. PMID- 29005969 TI - A Note on Alypin. PMID- 29005970 TI - Leishman-Donovan Infection in Europeans. PMID- 29005971 TI - Service Notes. PMID- 29005972 TI - De Senectute. PMID- 29005973 TI - Case of Fractured Pelvis. PMID- 29005974 TI - New Surgical Block, Calcutta Medical College. PMID- 29005975 TI - Cases of Recurrent Plague. PMID- 29005977 TI - Service Notes. PMID- 29005976 TI - Notes on Rupture of the Spleen (Second Series). PMID- 29005978 TI - Editorial Notes on Current Topics. PMID- 29005979 TI - Malarial Fevers among Europeans in Calcutta, and Their Differentiation from the Seven-Day Influenza-Like Fever. PMID- 29005980 TI - The Presence of Balantidium Coli in India. PMID- 29005981 TI - The History of the Indian Medical Service. PMID- 29005982 TI - The Etiology of Hill Diarrhoea. PMID- 29005983 TI - Rats and Plague at Giridih. PMID- 29005985 TI - Public Health. PMID- 29005984 TI - A Disclaimer. PMID- 29005986 TI - Editorial Notes on Current Topics. PMID- 29005987 TI - Gall-Stone. Cholelithotomy. PMID- 29005988 TI - Special Senses. PMID- 29005990 TI - Service Notes. PMID- 29005989 TI - Notes on the Last Plague Epidemic in Giridih. PMID- 29005991 TI - The Double Commissions. PMID- 29005992 TI - The Three Days Fever of Chitral : A Contribution to the Study of the Unclassed Fevers of India. PMID- 29005993 TI - Case of Piroplasmosis-Splenectomy Followed in Eight Months by Death. PMID- 29005994 TI - Use of Arsenic, &c., Hypodermically. PMID- 29005995 TI - The Epidemiology of Plague. PMID- 29005996 TI - Annus Medicus, 1905. PMID- 29005997 TI - Ivory Exostosis of Upper Jaw. PMID- 29005998 TI - Obstetrics and Midwifery. PMID- 29005999 TI - Foreign Extracts. PMID- 29006000 TI - Paratyphoid in India. PMID- 29006002 TI - Forms of Pyrexia Due to Leishman-Donovan's Bodies. PMID- 29006001 TI - A Case of Recurrent Plague. PMID- 29006003 TI - Leprosy and Fish Eating: Communicated. PMID- 29006004 TI - Perforation of Lung with a Sharp-Pointed Iron Rod-Recovery. PMID- 29006005 TI - Yaws. PMID- 29006007 TI - Editorial Notes on Current Topics. PMID- 29006006 TI - The Supply of Drinking Water in India and Its Connection with the Subsoil Water. PMID- 29006008 TI - Extraction of Cataract in the Capsule. PMID- 29006009 TI - Service Notes. PMID- 29006010 TI - The Treatments of Dysentery. PMID- 29006011 TI - Cryptorchides. PMID- 29006012 TI - A Specific for Whooping Cough. PMID- 29006013 TI - A Case of Stab Wound of the Spinal Cord. PMID- 29006014 TI - Yaws in Manipur State. PMID- 29006015 TI - Leishman-Donovan Infection in U. P. PMID- 29006016 TI - Extraction of Cataract in the Capsule v. the Ordinary or Capsule-Laceration Method. PMID- 29006017 TI - Round Worms and Appendicitis. PMID- 29006018 TI - On Couching of the Lens, as Practised by Native Practitioners in India. PMID- 29006019 TI - Bacillus Leprae, Gnats and Bugs. PMID- 29006021 TI - Special Senses. PMID- 29006020 TI - Aneurism in Child. PMID- 29006023 TI - A Manual for Junior I.M.S. Officers. PMID- 29006022 TI - Cataract Expression (Smith's Operation): Results in 175 Operations. PMID- 29006024 TI - Some Surgical Cases. PMID- 29006025 TI - Malarial Fevers in India. PMID- 29006026 TI - Three Unusual Cases of Hernia. PMID- 29006027 TI - Rats and Plague at Giridih. PMID- 29006029 TI - Service Notes. PMID- 29006028 TI - Irrigation in Cataract. PMID- 29006031 TI - Editorial Notes on Current Topics. PMID- 29006030 TI - A Note on the Value of Revaccination. PMID- 29006032 TI - Surgical Cases. PMID- 29006034 TI - On the Surgical Treatment of Prostatic Disease. PMID- 29006033 TI - The Balantidium Coli in India. PMID- 29006035 TI - Medicine. PMID- 29006036 TI - Some Practical Points about Vaccine Lymph. PMID- 29006037 TI - Japanese Medical Arrangements. PMID- 29006038 TI - The Daturas of Malaya. PMID- 29006039 TI - Cysticercus Cellulosae of Tongue: With a Note on the Helminthology of One of the Madras Jails. PMID- 29006041 TI - Diphtheria and Antitoxic Serum. PMID- 29006040 TI - Splenic Abscess in Malarial Fever. PMID- 29006042 TI - Extraction of Cataract in the Capsule. PMID- 29006043 TI - Extraction of the Lens in Its Capsule: An Experience of 311 Cases, and a Method of Recording Cases. PMID- 29006044 TI - A Further Note on Irrigation in Cataract Extraction. PMID- 29006045 TI - A Typhoid Fever Case (Paratyphoid) in the Ferozepore Jail. PMID- 29006047 TI - Corrigenda. AB - [This corrects the article on p. 163 in vol. 41.]. PMID- 29006046 TI - Curious Formation of Stone in the Bladder. PMID- 29006048 TI - Ten Days' Pigmentary Fever of Bengal. PMID- 29006049 TI - Extraction of Cataract in the Capsule. PMID- 29006050 TI - The Treatment of Syphilis. PMID- 29006052 TI - Doctors in Parliament. PMID- 29006051 TI - Medico-Legal Notes from Alipur. PMID- 29006053 TI - Notes on a Case of Fungus Disease of India (Mycetoma or Madura Foot). PMID- 29006055 TI - Notes on Ophthalmic Surgery. PMID- 29006054 TI - Medical Cases. PMID- 29006056 TI - Medical Cases. PMID- 29006057 TI - Relapsing Fever in the 109th Infantry. PMID- 29006058 TI - Hill Diarrhoea. PMID- 29006059 TI - Extraction of Cataract in the Capsule. PMID- 29006060 TI - An Old Account of Yaws. PMID- 29006061 TI - Enlargement of the Prostate. PMID- 29006063 TI - A Medical Visitor's Thanks. PMID- 29006062 TI - Intra-Capsular Irrigation in Cataract Extraction. PMID- 29006064 TI - The Government of India, the Medical Service and Their Critics. PMID- 29006065 TI - Puri as a Health Resort for Bengal. PMID- 29006066 TI - Service Notes. PMID- 29006067 TI - Notes on the Prevalence of Hill Diarrhoea in Maymyo. PMID- 29006068 TI - Notes on Insanity, with Illustrative Cases. PMID- 29006069 TI - Editorial Notes on Current Topics. PMID- 29006070 TI - Case of Litholopaxy. PMID- 29006071 TI - Surgical Cases from Swat Valley. PMID- 29006073 TI - Dechlorination and Dropsy. PMID- 29006072 TI - Opticociliary Neurectomy. PMID- 29006076 TI - I. M. S. and the Army List. PMID- 29006075 TI - A Midwifery Case. PMID- 29006074 TI - Plague in Madras. PMID- 29006077 TI - Revolver Bullet Wound. PMID- 29006078 TI - Large Abdominal Viscera. PMID- 29006079 TI - Editorial Notes on Current Topics. PMID- 29006080 TI - The Flaming Method of Sterilization. PMID- 29006081 TI - Service Notes. PMID- 29006082 TI - Epidemiology of Plague. PMID- 29006083 TI - Suprapubic Lithotomy. PMID- 29006084 TI - Foreign Body in Eye. PMID- 29006085 TI - Surgery of the Lung. PMID- 29006086 TI - Is Calcutta Seven-Day Fever Dengue? PMID- 29006087 TI - Public Health. PMID- 29006088 TI - The Spread of Plague. PMID- 29006089 TI - Malarial Fever with Aphasia. PMID- 29006090 TI - The Bed-Bug and the Transmission of Disease. PMID- 29006091 TI - An Appeal for Bed-Bugs. PMID- 29006092 TI - Irrigation in Cataract. PMID- 29006094 TI - An Account of Plague in Bengal. PMID- 29006093 TI - Extraction of Cataract in the Capsule v. the Ordinary or Capsule-Laceration Method. PMID- 29006095 TI - Permanganate Treatment of Snake-Bite. PMID- 29006096 TI - Correspondence. PMID- 29006097 TI - Some Surgical Cases. PMID- 29006099 TI - Editorial Notes on Current Topics. PMID- 29006098 TI - Some Observations on the Breeding Ground of the Common House-Fly and a Description of a Species of Moth-Fly. PMID- 29006101 TI - Service Notes. PMID- 29006100 TI - Cataract in the Capsule. PMID- 29006102 TI - The New Rules and Regulations for the Medical Faculty of the Calcutta University. PMID- 29006103 TI - A Case of Cobra Bite-Recovery. PMID- 29006104 TI - A Note on the Beneficial Effect of the Immediate Incision into Plague Glands. PMID- 29006106 TI - Service Notes. PMID- 29006105 TI - Medical Section of the Asiatic Society. PMID- 29006109 TI - Editorial Notes on Current Topics. PMID- 29006107 TI - Cholera Treated with Eucalyptus Oil. PMID- 29006108 TI - Two Cases of Ovariotomy for Tumours of Unusually Large Size. PMID- 29006110 TI - Beri-Beri in Sylhet Jail. PMID- 29006111 TI - Two Cases of Pneumonia with Unusual Complications. PMID- 29006113 TI - Mediterranean Fever in India. PMID- 29006112 TI - Enlarged Spleen and Its Treatment. PMID- 29006114 TI - Remittent Fever. PMID- 29006115 TI - A Case of Ovariotomy. PMID- 29006116 TI - On the Early Occurrence of Adipocere. PMID- 29006117 TI - The Surgery of Sarcomata. PMID- 29006119 TI - The Treatment of Snow-Blindness. PMID- 29006118 TI - Operations for Cataract. PMID- 29006120 TI - A Case of Ovariotomy. PMID- 29006121 TI - Season and Some Diseases in Madras. PMID- 29006122 TI - Xylol in Small-Pox. PMID- 29006123 TI - Hygiene, Military. PMID- 29006124 TI - Litholapaxy at Hyderabad, Sind. PMID- 29006125 TI - Hysterical Belch. PMID- 29006126 TI - Poisoning by Myrobalans. PMID- 29006127 TI - Distomum Crassum. PMID- 29006128 TI - Note on the "Anchylostomes" of Burma and Assam. PMID- 29006129 TI - Note on Intra-Capsular Cataract Extraction. PMID- 29006130 TI - Surgical Shock-Post-Operative. PMID- 29006131 TI - Bilious Typhus Relapsing Fever. PMID- 29006132 TI - Editorial Notes on Current Topics. PMID- 29006133 TI - Heteroplastic Ovarian Grafting. PMID- 29006135 TI - Surgery. PMID- 29006134 TI - The Hypodermic Use of Quinine. PMID- 29006136 TI - Service Notes. PMID- 29006137 TI - An Account of Plague in Bengal. PMID- 29006138 TI - Yaws in Manipur. PMID- 29006139 TI - Pneumococcic Infection of Joints. PMID- 29006140 TI - Spontaneous Rupture of Spleen. PMID- 29006141 TI - Sanitation. PMID- 29006142 TI - A Case of Osteomalacia. PMID- 29006143 TI - Post Graduate Courses of Study. PMID- 29006144 TI - Mosquitoes and Lime. PMID- 29006145 TI - Orbital Sarcoma, Kronlein's Operation. PMID- 29006146 TI - Visual Results of H. Smith's Operation. PMID- 29006147 TI - Plague at Giridih. PMID- 29006148 TI - Irrigation on Cataract Extraction. PMID- 29006149 TI - Medical Society. PMID- 29006150 TI - Medicine: Recent Articles on Pleural Effusion. PMID- 29006151 TI - Special Senses. PMID- 29006152 TI - Cataract Operations. PMID- 29006153 TI - Abscess Mistaken for Hernia. PMID- 29006154 TI - Editorial Notes on Current Topics. PMID- 29006155 TI - Manual of Aseptic Surgery. PMID- 29006156 TI - Development of Piroplasma Canis. PMID- 29006157 TI - Permanganate Treatment of Hydrophobia. PMID- 29006158 TI - Surgical Shock. PMID- 29006159 TI - Appendicitis in Indians. PMID- 29006160 TI - Service Notes. PMID- 29006161 TI - Cataract Operations. PMID- 29006163 TI - The Plague Commission's Report. PMID- 29006162 TI - Epidemiology of Plague. PMID- 29006164 TI - The Immunity of Calcutta-Proposed Explanations. PMID- 29006165 TI - An Experimental Investigation as to the Potency of Various Disinfectants against Rat-Fleas. PMID- 29006167 TI - Previous Epidemics of Plague in India. PMID- 29006166 TI - How Plague Is Spread. PMID- 29006168 TI - The World-Wide Distribution of Plague. PMID- 29006169 TI - Service Notes. PMID- 29006171 TI - Resolution on Plague in 1800. PMID- 29006170 TI - Rats and Plague. PMID- 29006172 TI - "Rat-Killing" for Prevention of Plague. PMID- 29006174 TI - Our Special Plague Number. PMID- 29006173 TI - Plague in the City of Madras. PMID- 29006176 TI - Plague and Rats. PMID- 29006175 TI - Report on the Effects of Rat Extermination on the Incidence of Plague in a Selected Area in Azamgarh City. PMID- 29006177 TI - Ten Years of Plague in India. PMID- 29006178 TI - Bed-Bugs and Leishman-Donovan Bodies. PMID- 29006179 TI - The Bombay Health Officer on Plague. PMID- 29006180 TI - Methods of the Spread of Plague. PMID- 29006181 TI - The Spread of Plague. PMID- 29006182 TI - Fleas, Rats and Plague. PMID- 29006183 TI - How Does Plague Spread. PMID- 29006184 TI - How Plague Is Spread. PMID- 29006186 TI - The Cataract in Capsule Operation. PMID- 29006185 TI - The Natural History of Plague. PMID- 29006187 TI - Current Topics. PMID- 29006188 TI - Corrigendum. AB - [This corrects the article on p. 432 in vol. 48.]. PMID- 29006189 TI - Service Notes. PMID- 29006190 TI - The 150th Anniversary of I. M. S. PMID- 29006191 TI - Notes on Some Cases. PMID- 29006193 TI - Cholera and "Epidemic Doctors". PMID- 29006192 TI - Observations on Myiasis in Bihar. PMID- 29006194 TI - Guttate or Nodular Keratitis. PMID- 29006195 TI - Ambulance Transport in Very Difficult Mountainous Country. PMID- 29006196 TI - Does Bilharzia (Schistosomiasis) Exist in India? PMID- 29006198 TI - Annus Medicus, 1913. PMID- 29006197 TI - A Lecture on Phylacogen. PMID- 29006199 TI - A Modification in Extirpation of the Lacrimal Sac. PMID- 29006200 TI - The Treatment of Fractures, Dislocations and Sprains by Massage. PMID- 29006201 TI - Surgn.-Genl. James Ellis. PMID- 29006202 TI - Emetine and Liver Abscess. PMID- 29006203 TI - Emetine and Dysentery. PMID- 29006204 TI - Emetine and Ipecacuanha: Their Amoebacidal Value in Pathogenic Amoebiasis. PMID- 29006205 TI - Medical Societies. PMID- 29006206 TI - Current Topics. PMID- 29006207 TI - Amoebic Dysentery in the Darjeeling District and Its Treatment. PMID- 29006208 TI - Emetine in Amoebic Dysentery. PMID- 29006209 TI - The Operative Treatment of Hepatic Abscess. PMID- 29006210 TI - The Poison of the Krait. PMID- 29006211 TI - The Emetine and Other Treatment of Amoebic Dysentery and Hepatitis Including Liver Abscess. PMID- 29006212 TI - Treatment of Liver Abscess. PMID- 29006213 TI - Delayed Chloroform Poisoning. PMID- 29006214 TI - An Experience in the Use of Emetine in the Treatment of Amoebic Dysentery. PMID- 29006215 TI - Psycho Analysis. PMID- 29006216 TI - A Series of 101 Cases of Abscess of the Liver. PMID- 29006218 TI - Service Notes. PMID- 29006217 TI - The Emetine Treatment of Dysentery. PMID- 29006219 TI - A Note on Three Cases Treated with Emetine. PMID- 29006220 TI - Notes on the Employment of Emetine in the Dharwar District. PMID- 29006221 TI - Emetine in Hepatitis, and Abscesses of the Liver. PMID- 29006223 TI - Special Emetine Number. PMID- 29006222 TI - The Removal of Wounded from the Firing Line in Mountain Warfare. PMID- 29006225 TI - Current Topics. PMID- 29006224 TI - Some Generalizations on the Scope, Construction and Administration of Central Asylums in India. PMID- 29006226 TI - The Treatment of the Earlier Stages of Senile Cataract. PMID- 29006227 TI - Radical Cure of Hernia. PMID- 29006228 TI - Intravenous Quinine in Malaria. PMID- 29006229 TI - Abdominal Wounds on the Battlefield. PMID- 29006230 TI - Anaesthetics in Hot Climates. PMID- 29006231 TI - Rice Gruel and Its Efficacy. PMID- 29006232 TI - Compulsory Vaccination. PMID- 29006233 TI - Digitate Tumours of the Prostate, Prostatectomy. PMID- 29006234 TI - Prevention and Treatment of Septic Wounds in Warfare. PMID- 29006236 TI - Asylum Dysentery. PMID- 29006235 TI - Two Cases of Anergic Stupor Treated with Thyroid Gland Extract. PMID- 29006237 TI - Radical Cure of Hydrocele. PMID- 29006238 TI - Notes of Two Cases of Hysteria in Males. PMID- 29006239 TI - Service Notes. PMID- 29006240 TI - Corrigenda. AB - [This corrects the article on p. 208 in vol. 49.]. PMID- 29006241 TI - An Epidemic of Mumps. PMID- 29006242 TI - The Diagnosis of Minor Fevers. PMID- 29006243 TI - Some Cases of Intestinal Obstruction. PMID- 29006244 TI - Dates of I. M. S. Commissions. PMID- 29006245 TI - Case of Absence of Uterus. PMID- 29006247 TI - "Lecithin" as an After-Treatment in Anaesthesia. PMID- 29006246 TI - Segregation and Kala-Azar: A Useful Measure. PMID- 29006248 TI - Ophthalmology in the Orient. PMID- 29006249 TI - Suspected Addison's Disease Aggravated by Ascaris Lumbricoides and Hysteria. PMID- 29006250 TI - The B. N. A. PMID- 29006251 TI - Decline of British Members. PMID- 29006252 TI - A New Pedicle Suture. PMID- 29006253 TI - Prevention of Malaria in the Troops of Our Indian Empire. PMID- 29006255 TI - The Treatment of Malaria: Opinions Asked for. PMID- 29006254 TI - Iodine as an Aid to Aseptic Vaccination. PMID- 29006256 TI - Current Topics. PMID- 29006257 TI - Reduced Fees for Medical Examination in Life Assurance. PMID- 29006258 TI - Service Notes. PMID- 29006259 TI - The I. M. S. Dinner in London. PMID- 29006260 TI - Radical Cure of Inguinal Hernia. PMID- 29006262 TI - The Calcutta Tropical School. PMID- 29006261 TI - Treatment of Cholera by the Intra-Peritoneal Injection of Iodine. PMID- 29006264 TI - The Medical Services in 1913. PMID- 29006263 TI - Cure for Snake-Bite by Actual Cautery. PMID- 29006265 TI - Anoci-Association and Cancer of the Cheek. PMID- 29006267 TI - The Prophylaxis and Treatment of Pre-Eclamptic Toxaemia and Eclampsia. PMID- 29006266 TI - "Use and Abuse of Pessaries": A Criticism. PMID- 29006268 TI - A Short Analysis of Eighty-Nine Cases of Epilepsy. PMID- 29006269 TI - A Bismuth Paste Injector. PMID- 29006270 TI - Transient Hemiplegia. PMID- 29006271 TI - Intestinal Parasites and Hill Peoples. PMID- 29006272 TI - The B. M. A. and I. M. S. PMID- 29006273 TI - An Analysis of 77 Cases of Placenta Praevia. PMID- 29006274 TI - Vaccine Treatment of Gonorrhoea. PMID- 29006275 TI - Insanity from Exhaustion. PMID- 29006276 TI - The Bombay Tropical School. PMID- 29006277 TI - The Surgery of Tubercular Glands. PMID- 29006278 TI - Zinc Rod in the Uterus. PMID- 29006279 TI - Two Cases of Abdominal Tumours: With Curious Complications. PMID- 29006280 TI - A Reply to Captain Barnardo's Letter. PMID- 29006281 TI - Service Notes. PMID- 29006282 TI - Current Topics. PMID- 29006283 TI - How to Keep Flies off Edible Articles for Sale. PMID- 29006284 TI - Appeal for Calcutta Tropical School. PMID- 29006285 TI - Mosquito-Malaria Hypothesis: Another Link in the Chain of Its History. PMID- 29006286 TI - A Portable High Pressure Sterilizer. PMID- 29006287 TI - Carriers in Ankylostomiasis. PMID- 29006288 TI - Entamoebic Dysentery. PMID- 29006289 TI - The Use and Abuse of Pessaries: A Clinical Lecture. PMID- 29006290 TI - Night-Blindness: Its Causes: Signs, Symptoms and Treatment. PMID- 29006291 TI - Acclimatisation of Northern Races in the Tropics. PMID- 29006293 TI - Service Notes. PMID- 29006292 TI - Gleanings from the Calcutta Post-Mortem Record: No. VIII (concluding) the Primary Causes of Death and the Most Frequent Errors of Diagnosis in 1,000 Medical Post Mortems. PMID- 29006294 TI - Calcutta School of Tropical Medicine. PMID- 29006295 TI - Transient Hemiplegia. PMID- 29006296 TI - Preliminary Note on Asino-Vaccine. PMID- 29006298 TI - Canarium Commune as an Addition to Milk in Infant Feeding. PMID- 29006297 TI - Salvarsan Poisoning. PMID- 29006299 TI - Current Topics. PMID- 29006300 TI - Two Cases of Relapsing Fever. PMID- 29006301 TI - I. M. S. in 1913. PMID- 29006302 TI - Venereal Disease in the Army of Our Indian Empire. PMID- 29006303 TI - Sir W. M. Osler and the English F.R.C.S. PMID- 29006305 TI - Subconjunctival Ecchymosis Due to Whooping Cough. PMID- 29006304 TI - Two Cases of Transposition of the Viscera. PMID- 29006306 TI - Service Notes. PMID- 29006308 TI - Crawford's History of I. M. S. PMID- 29006307 TI - Erratum: The Bombay Plague Laboratory: A Correction. AB - [This corrects the article on p. 198 in vol. 49.]. PMID- 29006310 TI - The Report of the Surgeon-General, American Army, 1913. PMID- 29006309 TI - Vaccination and Re-Vaccination. PMID- 29006311 TI - Pulmonary Tuberculosis Treated with Tuberculin. PMID- 29006312 TI - Review of 8th Plague Report. PMID- 29006313 TI - Plague Jottings. PMID- 29006315 TI - Retroversion of the Uterus and the 'Sling' Operation. PMID- 29006314 TI - The Nature of Jail Dysentery. PMID- 29006316 TI - Live Fish Acting as a Foreign Body in the Throat. PMID- 29006317 TI - Sweating the Scientist. PMID- 29006319 TI - Unusual Sequelae of Malarial Fever. PMID- 29006318 TI - Cocaine Eaters of Bombay. PMID- 29006320 TI - Treatment of Cholera by Emetine. PMID- 29006321 TI - Osseous New Growths. PMID- 29006322 TI - Fatal Case of Ophitoxaemia: Bite from the Common Indian Krait (Bungarus Caeruleus). Toxaemia. Death in 10 Hours. PMID- 29006323 TI - Current Topics. PMID- 29006324 TI - Ganja as a Cause of Insanity and Crime in Bengal. PMID- 29006325 TI - Current Topics. PMID- 29006326 TI - A Comparison between the Mental Processes in the Sane and in the Insane. PMID- 29006327 TI - Cow-Dung and Calf-Urine. PMID- 29006328 TI - The Prevention of Mental and Nervous Diseases. PMID- 29006329 TI - The Meaning of Insanity. PMID- 29006330 TI - Ophthalmology in the Orient. PMID- 29006331 TI - Iodine in Cholera. PMID- 29006332 TI - Insanity Statistical in India. PMID- 29006333 TI - Service Notes. PMID- 29006334 TI - The State Medical Faculty, Bengal. PMID- 29006335 TI - War Gifts. PMID- 29006336 TI - Absence of Uterus. PMID- 29006337 TI - Itinerating Dispensaries. PMID- 29006339 TI - Anaesthetics in Hot Climates. PMID- 29006338 TI - The Clear Pupil after Cataract Extraction. PMID- 29006340 TI - Weight of Vesical Stones. PMID- 29006341 TI - Remarks on Water-Supplies of Troops in India. PMID- 29006342 TI - Red Iodide of Mercury in Enlarged Malarial Spleen. PMID- 29006344 TI - Current Topics. PMID- 29006343 TI - Surgical Treatment of Goitre in Tibet. PMID- 29006345 TI - The Endemic Typhoid Area in the War. PMID- 29006346 TI - The Treatment of Malignant New Growths by Dr. De Keating-Hart's Method. PMID- 29006347 TI - Big Stones. PMID- 29006348 TI - Quinoidine in Solution. PMID- 29006349 TI - Anaemia among Indian Troops at Singapore. PMID- 29006350 TI - Service Notes. PMID- 29006351 TI - Devil Driving. Panchoa Devils-Classed as "Silent" and "Crying". PMID- 29006352 TI - Eruptions Complicating Superficial Wounds. PMID- 29006353 TI - The Proposed New General Hospital, Madras. PMID- 29006355 TI - Report of the General Hospital, Madras. PMID- 29006354 TI - Anagnostakis' Operation for Trichiasis. PMID- 29006357 TI - Emetine and Young Children. PMID- 29006356 TI - Case of Echis Toxaemia: Echis One Foot Two Inches Long. Death in 12 Hours. PMID- 29006358 TI - Ruptured Extra Uterine Pregnancy: 5-6 Months. Laparotomy. Delayed Chloroform Poisoning? Recovery. PMID- 29006359 TI - The Treatment of Dysentery. PMID- 29006360 TI - Ascaris Lumbricoides Infection in Malabar District. PMID- 29006361 TI - Iodine Method of Vaccination. PMID- 29006363 TI - Current Topics. PMID- 29006362 TI - Rupture of the Spleen. PMID- 29006364 TI - Anaesthetics in Hot Climates. PMID- 29006366 TI - Service Notes. PMID- 29006365 TI - Irrigation, after Cataract: Analysis of 102 Consecutive Cases. PMID- 29006367 TI - Bombay Tropical School. PMID- 29006368 TI - Catarrhal Jaundice in Calcutta. PMID- 29006369 TI - Psoas Abscess Treated by Pneumococcal Vaccine. PMID- 29006370 TI - Ruptured Spleen, Splenectomy : Recovery. PMID- 29006371 TI - A Thousand Cataracts Performed in Six Weeks at Shikarpur. PMID- 29006372 TI - Cataract in the Capsule with Notes on 1,137 Consecutive Operations. PMID- 29006373 TI - Furlough Allowances in I. M. S. PMID- 29006374 TI - A History of Medicine. PMID- 29006375 TI - Peritoneal Cyst of Traumatic Origin and Other Cases. PMID- 29006376 TI - Cases of Hypo-Thyroidism. PMID- 29006377 TI - A Case of "Simple, Non-Infective" Thrombosis. PMID- 29006379 TI - Current Topics. PMID- 29006378 TI - Cases Treated in the Ripon Hospital, Ahmednagar: Extravasation of Urine with Gangrene. PMID- 29006380 TI - Corrigendum. AB - [This corrects the article on p. 365d in vol. 49.]. PMID- 29006381 TI - Training of I.M.S. Officers. PMID- 29006382 TI - Service Notes. PMID- 29006383 TI - Intussusception. PMID- 29006384 TI - Pus Inoculations. PMID- 29006386 TI - The Bombay Tropical School. PMID- 29006385 TI - A Short Note on Nasha Fever. PMID- 29006387 TI - Ligation of Broad Pedicles. PMID- 29006388 TI - Chloroform Inhalation in Whooping Cough. PMID- 29006389 TI - Studies in Malaria. PMID- 29006390 TI - Plague Prophylaxis. PMID- 29006391 TI - Delayed Chloroform Poisoning. PMID- 29006392 TI - Sclero-Corneal Trephining for Staphyloma. PMID- 29006394 TI - Asino-Vaccine. PMID- 29006393 TI - Krait Identification. PMID- 29006395 TI - Chronic Intestinal Stasis. PMID- 29006396 TI - Laboratory and Clinical Work. PMID- 29006397 TI - Surgery at Rangoon. PMID- 29006398 TI - Vesico-Vaginal Fistula. PMID- 29006399 TI - Iodine in the Treatment of Plague. PMID- 29006401 TI - The Bombay Tropical Medical School. PMID- 29006400 TI - Service Notes. PMID- 29006403 TI - Ascaris Infection. PMID- 29006402 TI - Abdominal Surprises. PMID- 29006404 TI - Prolapse of the Uterus. PMID- 29006405 TI - Current Topics. PMID- 29006406 TI - A Case of Bilharzia Disease. PMID- 29006408 TI - Furlough in the I. M. S. PMID- 29006407 TI - Itinerating Dispensaries. PMID- 29006409 TI - Agra Medical Missionary Training Institute. PMID- 29006410 TI - Epidemic Dropsy in the Darjeeling District. PMID- 29006411 TI - Multilocular Cyst of Neck. PMID- 29006412 TI - Some Observations on the Uses of the Operation of Appendicostomy. PMID- 29006413 TI - Some Observations on Cataract Extraction. PMID- 29006414 TI - Dementia Praecox in India. PMID- 29006415 TI - Typhus Fever in Northern India. PMID- 29006417 TI - Therapeutic Notes and Preparations, &c. PMID- 29006416 TI - An Outbreak of Typhus Fever in Peshawar. PMID- 29006418 TI - Blackwater Fever. PMID- 29006419 TI - Some Effects from Stinging by a Hornet (Vespa Orientalis). PMID- 29006420 TI - Kala-Azar in Patna. PMID- 29006422 TI - Service Notes. PMID- 29006421 TI - The Use of Adrenalin in Rickets. PMID- 29006424 TI - The "Bossi" Cure. PMID- 29006423 TI - The Bombay Medical Congress. PMID- 29006425 TI - Current Topics. PMID- 29006426 TI - Calcium Chloride and Its Action on the Coagulability of Blood. PMID- 29006427 TI - Service Notes. PMID- 29006428 TI - Motor Vehicles for Civil Surgeons. PMID- 29006429 TI - Spirochaete Fever. PMID- 29006430 TI - The Use of Gloves in Surgery. PMID- 29006431 TI - Kala-Azar and Blackwater Fever. PMID- 29006432 TI - Fleas and Disinfectants. PMID- 29006433 TI - The Use of Ipecacuanha in Hepatitis. PMID- 29006434 TI - Epidemic Dropsy in the Darjeeling District. PMID- 29006435 TI - On a New Test for Differentiation of the Bacilli of the Typhoid Group. PMID- 29006436 TI - Surgical Asepsis in Its Simpler Forms. PMID- 29006437 TI - Current Topics. PMID- 29006439 TI - A Note on Lithotrites. PMID- 29006438 TI - On the Probable Identity of Beri-Beri and Epidemic Dropsy. PMID- 29006440 TI - Medical Education in India. PMID- 29006441 TI - Some Suggestions in Connection with the Requisite Apparatus. PMID- 29006443 TI - Motor Cars for Civil Surgeons. PMID- 29006442 TI - Report on 50 Cases of Beri-Beri in the Reformatory School, Alipur. PMID- 29006444 TI - A Case of Prostatectomy. PMID- 29006445 TI - A Case of Gonorrhoeal Septicaemia. PMID- 29006446 TI - Viperine Snake-Poisoning. PMID- 29006447 TI - Psychology, Medicine and So-Called Christian Science. PMID- 29006448 TI - A New Method of Carrying Wounded off the Field on Service. PMID- 29006449 TI - Malarial Pneumonia. PMID- 29006450 TI - Haemoglobinuria and Quinine Sulphate. PMID- 29006451 TI - A Case of Ovariotomy. PMID- 29006452 TI - Report on an Epidemic of Dengue Consisting of Both a Three-Day and Seven-Day Fever Type among the 15th Lancers at Sialkot, 1907. PMID- 29006453 TI - Cholera Diffusion by Flies. PMID- 29006454 TI - Service Notes. PMID- 29006455 TI - Some Notes and Observations on 310 Consecutive Operations for Extirpation of the Lachrymal Sac. PMID- 29006457 TI - Current Topics. PMID- 29006456 TI - Preliminary Note on the Etiology of Blackwater Fever. PMID- 29006458 TI - Epidemic Dropsy. PMID- 29006459 TI - Quinine and Pregnancy. PMID- 29006460 TI - Bombay Notes. PMID- 29006461 TI - Foreign Extracts. PMID- 29006462 TI - Incineration in Military Station. PMID- 29006463 TI - Current Topics. PMID- 29006464 TI - Is Ordinary (Pneumococcal) Pneumonia an Infectious Disease? PMID- 29006465 TI - A Radical Change in Methods of Dosage. PMID- 29006467 TI - Quinine Sulphate and Blackwater Fever. PMID- 29006466 TI - The "Locking-Grip" of Lithotrites. PMID- 29006468 TI - Memorial to the Late Professor Annandale. PMID- 29006470 TI - Experiments on "Rat Entermination". PMID- 29006469 TI - The Subjective Mind. PMID- 29006472 TI - Service Notes. PMID- 29006471 TI - Complete Rupture of Uterus. PMID- 29006473 TI - Broad Ligament Cyst Weighing 130lbs. Removal; Recovery. PMID- 29006474 TI - A Case of "Surra" in Manipur. PMID- 29006475 TI - Cases from the Medical College Hospital, Calcutta: Special Report of the Medical College Hospital for 1907. PMID- 29006476 TI - A Case of Abscess of the Spleen. PMID- 29006477 TI - The Advance of Surgery in India. PMID- 29006478 TI - Dermatology. PMID- 29006479 TI - Correspondence. PMID- 29006480 TI - Therapeutic Notes, &c. PMID- 29006482 TI - Malaria and Empire Decay. PMID- 29006481 TI - A Bombay Letter. PMID- 29006483 TI - Service Notes. PMID- 29006485 TI - A Case of Calcareous Degeneration of the Tunica Vaginalis. PMID- 29006484 TI - The Training of Hospital Dressers. PMID- 29006487 TI - Annus Medicus, 1907. PMID- 29006486 TI - The High Mortality Due to Child-Bearing Amongst Burmese Women. PMID- 29006489 TI - Two Cases of Splenectomy. PMID- 29006490 TI - Elephantiasis Operations: An Improved Method of Grafting. PMID- 29006488 TI - The Medical Services in the Mutiny. PMID- 29006492 TI - Note on the Treatment and Diagnosis of Gonorrhoea in Women. PMID- 29006491 TI - Some Practical Notes on the Use of Rubber Gloves. PMID- 29006494 TI - Current Topics. PMID- 29006493 TI - A Critical Analysis of the Etiology and Symptomatology of the Three-Day Fever of Chitral; and an Analogy between This Condition and Dengue Fever. PMID- 29006495 TI - Notes on Forster's Vaccine Treatment of Dysentery. PMID- 29006496 TI - Disinfectants and Their Co-Efficients. PMID- 29006497 TI - Urotropine in Night-Blindness. PMID- 29006498 TI - Note on the Phagocytosis in Black-Water Fever. PMID- 29006499 TI - A Preliminary Note on Blood Pressures as a Guide in Transfusion for Cholera. PMID- 29006500 TI - A Convenient Capsule for Sending Infective Material to the Laboratory. PMID- 29006501 TI - Quinine in Pregnancy. PMID- 29006502 TI - Current Topics. PMID- 29006503 TI - Therapeutic Notes and Preparations. PMID- 29006504 TI - Erratum: A Correction. AB - [This corrects the article on p. 14 in vol. 43.]. PMID- 29006505 TI - Is the Poison of Scarlet Fever Present in India? PMID- 29006506 TI - Quinine in Pregnancy. PMID- 29006507 TI - Vaccines in India. PMID- 29006508 TI - Service Notes. PMID- 29006509 TI - Fleas and Disinfectants. PMID- 29006510 TI - The Treatment of Enlargement of Spleen with Hypodermic Injection of Turpentine. PMID- 29006511 TI - A Bombay Letter. PMID- 29006512 TI - Remarks on the Vaccine Treatment of Colicystitis. PMID- 29006513 TI - The Etiology of Yaws. PMID- 29006515 TI - Motor Vehicles for Civil Surgeons. PMID- 29006514 TI - Account of the Occurrence of "Epidemic Dropsy" in Comilla Jail. PMID- 29006517 TI - Current Topics. PMID- 29006516 TI - Some Notes and Observations on 310 Consecutive Operations for Extirpation of the Lachrymal Sac. PMID- 29006518 TI - Therapeutic Notes, &c. PMID- 29006519 TI - Treatment of Leprosy with X-Rays and High Frequency. PMID- 29006520 TI - Enquiries Regarding the Mode of Spread and the Prevention of Plague. PMID- 29006521 TI - Enteric Fever in the Native Army. PMID- 29006522 TI - A Disclaimer. PMID- 29006523 TI - Medical Society. PMID- 29006524 TI - Rat-Destruction Operations in the Punjab. PMID- 29006525 TI - Notes on Judicial Hanging. PMID- 29006527 TI - The Need of a Medical Registration Act for India. PMID- 29006526 TI - Epidemic Pneumonia on N.-W. Frontier. PMID- 29006528 TI - Service Notes. PMID- 29006530 TI - Further Observations on the Flea-Killing Power of Certain Chemicals. PMID- 29006529 TI - Talma's Operation for Ascites. PMID- 29006531 TI - Current Topics. PMID- 29006532 TI - The Preparation of Whey. PMID- 29006533 TI - Outbreak of Epidemic Dropsy in the Lunatic Asylum, Dacca, in March 1908. PMID- 29006534 TI - Surgical Cases. PMID- 29006535 TI - Tropical Chicken-Pox, Modified Small-Pox, or a Third Eruptive Fever. PMID- 29006536 TI - Some Remarks on Lobar Pneumonia. PMID- 29006537 TI - Cases of Liver Abscess. PMID- 29006538 TI - A Case of Abscess of the Spleen. PMID- 29006539 TI - The Factory Report as It Affects the Civil Surgeon. PMID- 29006540 TI - Hornet Sting. PMID- 29006541 TI - Large Cysts. PMID- 29006544 TI - The Metabolism of Bengalis. PMID- 29006542 TI - Rat Destruction in Kamptee. PMID- 29006546 TI - Current Topics. PMID- 29006545 TI - Service Notes. PMID- 29006547 TI - Service Notes. PMID- 29006548 TI - Captain Sumner's Recent Article. PMID- 29006549 TI - List of Surgeons in India in 1749. PMID- 29006550 TI - A Case of Caesarean Section: Secunderabad. PMID- 29006551 TI - Some Remarks on the Report on Plague in Calcutta for the Year Ending 30th June 1907. PMID- 29006552 TI - Note on a Parasite in the Sparrow. PMID- 29006554 TI - Case of Pyloroplasty. PMID- 29006553 TI - Vaccination and Pertussis. PMID- 29006555 TI - The Proposed Medical Congress at Bombay. PMID- 29006556 TI - Note on the Value of Large Quantities of Hypertonic Salt Solutions in Transfusion for Cholera. PMID- 29006557 TI - Medical Society. PMID- 29006558 TI - Crude Views on the Use of X-Rays. PMID- 29006559 TI - An Epidemic of Dropsy. PMID- 29006561 TI - Appeal for Funds to Build a Hostel for Indians in Connection with the Pasteur Institute of India, at Kasauli. PMID- 29006560 TI - Epidemic Dropsy or Beri-Beri in Eastern Bengal. PMID- 29006562 TI - Service Notes. PMID- 29006564 TI - A Method of Operating for Umbilical Hernia. PMID- 29006563 TI - The Duration of the Immunity Conferred by Plague Inoculation. PMID- 29006565 TI - Pyorrhoea Alveolaris; from a Tropical Standpoint: Part III.-Sequelae. Treatment. PMID- 29006566 TI - Quinine in Pregnancy. PMID- 29006567 TI - A Case of Pneumothorax. PMID- 29006569 TI - Gleanings from the Calcutta Post-Mortem Records. PMID- 29006570 TI - Spinal Analgesia. PMID- 29006571 TI - A Case of Blood Cyst of the Peritoneum. PMID- 29006572 TI - Medical Society: Asiatic Society of Bengal. PMID- 29006573 TI - Current Topics. PMID- 29006574 TI - Notes on the Recent Epidemic of Phagedaenic Ulcers in Assam, with Remarks on a Bacillus Present in the Sores. PMID- 29006575 TI - Twenty Years of Puerperal Eclampsia at the Government Maternity Hospital, Madras. PMID- 29006576 TI - Rupture of Bladder from Kick by a Bullock. PMID- 29006577 TI - Chauffeur's Fracture. PMID- 29006578 TI - Sprue and Allied Disorders. PMID- 29006579 TI - Liver Abscess in a Female. PMID- 29006580 TI - Pyorrhoea Alveolaris; from a Tropical Standpoint. PMID- 29006581 TI - A Preliminary Note on Spirochaetosis. PMID- 29006582 TI - The I. M. S. Pension at 271/2 Years Service. PMID- 29006583 TI - The Surgery of Elephantiasis. PMID- 29006584 TI - Rupture of Spleen. PMID- 29006585 TI - Quinine and Pregnancy. PMID- 29006586 TI - A Phantom Tumour. PMID- 29006587 TI - Service Notes. PMID- 29006588 TI - Diabetes in India. PMID- 29006589 TI - The Treatment of Uncomplicated Lobar Pneumonia. PMID- 29006590 TI - Prostatectomy for Retention of Urine. PMID- 29006591 TI - Current Topics. PMID- 29006593 TI - The Treatment of Immature Cataract. PMID- 29006594 TI - The Locking-Grip of Lithotrites. PMID- 29006595 TI - Methylene-Blue in Fevers. PMID- 29006596 TI - Wound of the Abdomen. PMID- 29006597 TI - The Value of Taking the Specific Gravity of the Blood during Saline Transfusion in Cholera. PMID- 29006598 TI - The Serum Treatment of Cerebro-Spinal Fever. PMID- 29006599 TI - Treatment of Hydrocele. PMID- 29006600 TI - On the Treatment of Smallpox by Large Doses of Hydrarg. C. Creta. PMID- 29006601 TI - Observations on Endemic Cretinism in the Chitral and Gilgit Valleys. PMID- 29006602 TI - Treatment of Pneumonia. PMID- 29006603 TI - A Simple Apparatus for Distilling Water. PMID- 29006604 TI - Quinine in Uterine Inertia (A Case). PMID- 29006605 TI - Service Notes. PMID- 29006606 TI - Current Topics. PMID- 29006608 TI - The Treatment of Injuries of and about the Elbow Joint. PMID- 29006609 TI - A Forgotten Service Grievance. PMID- 29006610 TI - Quinine and Pregnancy. PMID- 29006611 TI - Cancer in Travancore: A Resume of 1,700 Cases. PMID- 29006613 TI - I. M. S. Pensions and Pay. PMID- 29006612 TI - The Bite of Echis Carinata. PMID- 29006614 TI - X-Rays as an Aid to Diagnosis in Some Common Surgical Conditions. PMID- 29006615 TI - Corrigendum. AB - [This corrects the article on p. 479 in vol. 46.]. PMID- 29006616 TI - Medieal Service in India. PMID- 29006619 TI - Cholera Prophylactic Vaccination: An Experiment in a Viliage during an Epidemic. PMID- 29006617 TI - Paka Oil in Mustard Oil as an Adulterant. PMID- 29006620 TI - The Economic Value of Anti-Cholera Inoculation. PMID- 29006622 TI - Surgical Emphysema, Complicating Influenza. PMID- 29006621 TI - Case of Hydatid Cyst. PMID- 29006623 TI - A Case of Ophitoxaemia-Snake Poisoning: Snake Identified, Echis Carinata, by the Natural History Society, Bombay. - Recovery. PMID- 29006624 TI - Midwifery Impressions. PMID- 29006625 TI - Clinical Cases. PMID- 29006626 TI - Service Notes. PMID- 29006627 TI - Wounds Infected with Bacillus Pyocyaneus. PMID- 29006628 TI - Diabetes in Madras. PMID- 29006629 TI - The Modern Theory of Renal Excretion. PMID- 29006630 TI - A Case of Ectopic Gestution Which Burst into the Rectum. PMID- 29006631 TI - Current Topics. PMID- 29006632 TI - A Case of Daboia Poisoning. PMID- 29006634 TI - Colloidal Preparations in Modern Treatment. Colloidal Sulphur and Mercury in Specific Arthritis. PMID- 29006633 TI - Service Notes. PMID- 29006635 TI - A Plea for Simplicity in the Prevention and Cure of Bacterial Infection. PMID- 29006636 TI - Oriental Sore or Baghdad Boil. PMID- 29006637 TI - The Temporary Officer in War. PMID- 29006638 TI - "Protein Shock" and Intravenous Vaccine Therapy. PMID- 29006639 TI - Some Impressions of a Visit to the Tuberculosis Institute, Madras. PMID- 29006640 TI - Treatment of Fracture of the Patella. PMID- 29006641 TI - How a Snake Catches His Prey. PMID- 29006642 TI - Current Topics. PMID- 29006643 TI - Malunion in a Fractured Tibia, Due to the Tendon of the Tibialis Anticus. PMID- 29006644 TI - Snake Venom as a Therapeutic Agent. PMID- 29006645 TI - Demonstration of Flagella of Spirochaeta Carteri. PMID- 29006646 TI - Flying Insects from the Rectum. PMID- 29006647 TI - An Address to the Students of the Medical College, Calcutta. PMID- 29006648 TI - Hydrogen Peroxide in Cholera. PMID- 29006649 TI - The Heart on the Right Side. PMID- 29006651 TI - Anaphylaxis. PMID- 29006650 TI - A Case of Raptured Abdominal Wall. PMID- 29006653 TI - Further Observations on Tetanus. PMID- 29006652 TI - Good Digestion Waits upon Appetite. PMID- 29006654 TI - Recent Researches on Hookworm Infection in Indonesia. PMID- 29006655 TI - Surgical Problems and Difficulties in the Tropics. PMID- 29006656 TI - Generalised Vaccinia in Burma. PMID- 29006657 TI - Service Notes. PMID- 29006658 TI - Current Topics. PMID- 29006659 TI - Yaws in India. PMID- 29006660 TI - Sand-Fly Fever and Its Relationship to Dengue. PMID- 29006661 TI - Diptheroid Infection in Influenza. PMID- 29006662 TI - Service Notes. PMID- 29006663 TI - Remarks on the Influence of Abdominal Lesions on the Respiratory System. PMID- 29006664 TI - Current Topics. PMID- 29006665 TI - The Efficacy of Quinine in Malaria. PMID- 29006666 TI - Specific Fever or Syphilitic Septicaemia. PMID- 29006667 TI - Calculi of the Prostate. PMID- 29006668 TI - Iodine in Cholera. PMID- 29006669 TI - Schistosomiasis in India. PMID- 29006670 TI - Carbolic Acid Gargles in Diphtheria. PMID- 29006671 TI - A Civil Surgeon at Headquarters in Upper Burma. PMID- 29006672 TI - Kidney Disease and Kidney Function. PMID- 29006673 TI - Emetine Injections in Sprue. PMID- 29006674 TI - Mica Flakes as Substitute for Glass Cover-Slips. PMID- 29006675 TI - The Indian Medical Service. PMID- 29006676 TI - On the Latest Method of Treatment of Cholera. PMID- 29006677 TI - Hypnotism. PMID- 29006678 TI - The Treatment of Syphilis and the Wassermann Reaction Thereafter. PMID- 29006679 TI - A Complete Transposition of the Viscera. PMID- 29006680 TI - Service Notes. PMID- 29006681 TI - The Calcutta Eye Hospital. PMID- 29006682 TI - Worms. PMID- 29006683 TI - The New Treatment of Chronic Parenchymat Us Nephritis. PMID- 29006684 TI - A Note on the Prevalence of the New Disease (Influenza) in Coorg, Symptoms, Treatment and Prevention. PMID- 29006685 TI - Punjab Lunatic Asylum. PMID- 29006686 TI - An Interesting Case of Parenchymatous Nephritis. PMID- 29006687 TI - Exchange. PMID- 29006688 TI - Some Points of Practical Importance in the Operation of Sclero-Corneal Trephining by Elliot's Method. PMID- 29006690 TI - Current Topics. PMID- 29006689 TI - Report on the Pandemic of Influenza (La Grippe) in the Province of Coorg during the Year 1918. PMID- 29006691 TI - Glaucoma. PMID- 29006692 TI - Plague in India in 1618: The Rat Theory Foreshadowed. PMID- 29006693 TI - Schistosomiasis in India. PMID- 29006694 TI - Dengue or Three-Day Fever. PMID- 29006695 TI - Congenital Abnormalities: Case No. 1. PMID- 29006696 TI - A Fly-Proof Latrine Seat for Indians. PMID- 29006697 TI - Unusual Effects of Quinine. PMID- 29006698 TI - Mathematicians in the I.M.S. PMID- 29006699 TI - Birthday Honours. PMID- 29006700 TI - The Disinfection of Jails and Asylums with Chlorine Solution. PMID- 29006701 TI - Service Notes. PMID- 29006702 TI - Report on Kala-Azar Cases Treated in the Nowgong Earle Hospital, Assam, Since 1917. PMID- 29006703 TI - Hydrogen Peroxide in Cholera. PMID- 29006704 TI - Six Cases of Kodra Poisoning. PMID- 29006705 TI - Flying Intestinal Worms. PMID- 29006706 TI - The Influence of 1: 1000 Platinum Solution on Pneumonic Infections. PMID- 29006707 TI - The Complement Fixation Test in the Diagnosis of Tuberculosis. PMID- 29006709 TI - Current Topics. PMID- 29006708 TI - Report on the Prevalence of Malaria and Anopheline Mosquitoes and Measures Recommended for the Prevention of Malaria in Mercara. PMID- 29006710 TI - Maternity and Child-Welfare. PMID- 29006711 TI - Erratum: Plans of Fly-Proof Latrine Seat for Indians. AB - [This corrects the article on p. 370 in vol. 54.]. PMID- 29006712 TI - Treatment of Influenza. PMID- 29006714 TI - Current Topics. PMID- 29006713 TI - The Eradication of Ankylostomiasis in Ceylon. PMID- 29006715 TI - Medical Students and the War. PMID- 29006716 TI - The End of the War and Leave. PMID- 29006717 TI - A Simplified Technique for Agglutination-Reactions ("Widals"). PMID- 29006718 TI - Treatment of Baghdad Boils by Ionisation. PMID- 29006719 TI - Gunshot Wounds of the Knee-Joint with Septic Arthritis. PMID- 29006720 TI - Hookworm Disease among Labourers in the Tea Gardens of the Duars. PMID- 29006721 TI - Medical Societies. PMID- 29006723 TI - Service Notes. PMID- 29006722 TI - The Polyneuritic Psychosis (Korsakoff' Syndrome). PMID- 29006724 TI - Report of the Government Ophthalmic Hospital, Madras (for the Year 1917). PMID- 29006726 TI - Influenza in Bombay. PMID- 29006725 TI - Pneumonia: Heart Tonics in. PMID- 29006727 TI - A Suggested Antidote for Snake and Scorpion Venom. PMID- 29006729 TI - Current Topics. PMID- 29006728 TI - Inflammatory Conditions Due to Calcified Remains of Guinea Worms. PMID- 29006731 TI - The Quest for Quinine. PMID- 29006730 TI - Reatment of Malaria by Quinine: Failure of "Splenox". PMID- 29006732 TI - Service Notes. PMID- 29006733 TI - Malaria Prevention in Malacca: Lecture on Destruction of Mosquitoes. PMID- 29006734 TI - Quinine in Malaria Prophylaxis. PMID- 29006735 TI - Quinine Prophylaxis in Malaria. PMID- 29006736 TI - Report on the Treatment of Malaria: Abstract of 2,460 Cases-War Office Investigations. PMID- 29006737 TI - Notes on Plague Inoculation. PMID- 29006738 TI - Rat-Killing Operations of Mahableshwar. PMID- 29006739 TI - Tartar Emetic Treatment in Malaria and Kala-Azar. PMID- 29006740 TI - Medical Society. PMID- 29006741 TI - Current Topics. PMID- 29006742 TI - A Case of Ectopic Gestation Burst into the Rectum (4 to 5 Months). PMID- 29006743 TI - Plague and Rat Destruction. PMID- 29006744 TI - A Case of Post-Operative Tetanus. PMID- 29006746 TI - Service Notes. PMID- 29006745 TI - Notes on Cases of Surgical Interest. PMID- 29006747 TI - Discussion on the Treatment of Malaria. PMID- 29006749 TI - Sanitary Commissioner's Report: India. PMID- 29006748 TI - Cerebrospinal Fever at Gaya. PMID- 29006751 TI - Radishes in Dropsy. PMID- 29006750 TI - A Case of Eclampsia. PMID- 29006752 TI - Medical Students and Medical Schools in India. PMID- 29006753 TI - Anti-Malarial Measures in Relation to the Human Carrier. PMID- 29006754 TI - Rats and Plague. PMID- 29006756 TI - Leishmania Sores and Antimony. PMID- 29006755 TI - A Note on Teeth in the Indian Army. PMID- 29006757 TI - Treatment of Rat-Bite Fever with Injections of Cacodylate of Soda. PMID- 29006759 TI - Mr. Montagu and the I. M. S. PMID- 29006758 TI - Sunstroke or Heatstroke. PMID- 29006760 TI - I. M. S. and the Honour Lists. PMID- 29006761 TI - Medical Society. PMID- 29006762 TI - Wanted a Diagnosis. PMID- 29006764 TI - The Syphilitic Factor Is So-Called Chronic Rheumatism. PMID- 29006763 TI - Treatment of Vesico-Vaginal Fistulae. PMID- 29006765 TI - Heights and Weights: A Help to Recruiting Officers. PMID- 29006766 TI - Current Topics. PMID- 29006767 TI - Service Notes. PMID- 29006768 TI - Epidemic of Cases of Oedema Amongst West African Porters. PMID- 29006769 TI - Further Notes on Margosic Acid and Its Salts and Observations on Their Clinical Use. PMID- 29006770 TI - A Case of Primary Absecss of the Spleen. PMID- 29006772 TI - Current Topics. PMID- 29006771 TI - An Unclassified Form of Long Continued Pyrexia in Mesopotamia: (? Disseminated Nocardiosis) Preliminary Report. PMID- 29006774 TI - Service Notes. PMID- 29006773 TI - The Principles of Military Orthopaedics: With Notes on the Constitution of an Orthopaedic Hospital. PMID- 29006775 TI - The Syphilitic Factor in Aortic Incompetence in Bengalis. PMID- 29006776 TI - Treatment of Beri-Beri. PMID- 29006777 TI - Notes on Cases Treated with Radium. PMID- 29006778 TI - Sir Pardey Lukis Memorial Fund: Fresh List of Subscribers. PMID- 29006779 TI - The Thorough Treatment of Malaria. PMID- 29006780 TI - Clinical Notes from Government Maternity Hospital, Madras. PMID- 29006782 TI - Report, General Hospital, Madras. PMID- 29006781 TI - Case of Itching. PMID- 29006783 TI - Case of Syphilitic Fever. PMID- 29006784 TI - E. C. Hare and Quinine. PMID- 29006785 TI - A Tenacious Case of Tetanus and the Effect of Anti-Serum. PMID- 29006786 TI - Modification of Leishman's Stain. PMID- 29006787 TI - Urea Quinine. PMID- 29006788 TI - Urea Quinine. PMID- 29006789 TI - Cases of Leprosy in Bangkok Treated with Sodium Gynocardate and Sodium Gynocardate "A." PMID- 29006790 TI - On a New Method of Standardization of Disinfectants. PMID- 29006791 TI - Blackwater Fever in the Agency of Ganjam District. PMID- 29006792 TI - Current Topics. PMID- 29006793 TI - The Anti-Hookworm Campaign. PMID- 29006795 TI - Medical Society. PMID- 29006794 TI - Gnathostomum Siamense or Gnathostoma Spinigerum, Owen. PMID- 29006797 TI - Urea Quinine. PMID- 29006796 TI - "Chuharia" Ulcer in Mayurbhanj and Other Neighbouring Parts of Orissa. PMID- 29006798 TI - Quinine Prophylaxis. PMID- 29006799 TI - Service Notes. PMID- 29006800 TI - The Etiology of Sprue. PMID- 29006802 TI - Service Notes. PMID- 29006801 TI - Notes on War Surgery from the Indian Troops War Hospital, Dehra Dun. PMID- 29006804 TI - Is Aspirin Dangerous. PMID- 29006803 TI - X-Ray Work in an Indian General Hospital in Mesopotamia. PMID- 29006805 TI - Jellyfish Poisoning. PMID- 29006806 TI - A Civil Surgeon "On Tour" in Upper Burma. PMID- 29006807 TI - Some Observations on "Influenza". PMID- 29006808 TI - Analysis of 1,200 Consecutive Abdominal Operations Performed for Gynaecological Disease on Burmese Females. PMID- 29006809 TI - Annus Medicus, 1918. PMID- 29006811 TI - Hospital Equipment Wanted. PMID- 29006810 TI - The Treatment of Panophthalmitis. PMID- 29006812 TI - Circumcision. PMID- 29006813 TI - The Influenza Pandemic. PMID- 29006814 TI - A Dividing Stretcher. PMID- 29006815 TI - Service Notes. PMID- 29006816 TI - An Unclassified Form of Long-Continued Pyrexia in Mesopotamia: ? Disseminated Nocardiosis. PMID- 29006817 TI - Current Topics. PMID- 29006818 TI - Service Notes. PMID- 29006819 TI - Full Pay Leave. PMID- 29006820 TI - Charaka Samhita. PMID- 29006822 TI - Cardiac Massage in Chloroform Poisoning. PMID- 29006821 TI - Current Topics. PMID- 29006823 TI - X-Ray Observations to Determine the Time Food Remains in the Stomach. PMID- 29006824 TI - Ether as an Anaesthetic. PMID- 29006825 TI - Cellulose and Chronic Constipation. PMID- 29006826 TI - Bug-Eating and Its Results. PMID- 29006828 TI - A New Technique of Heart Massage with a Case of Resuscitation. PMID- 29006827 TI - Some Points in Connection with War Injuries of Peripheral Nerves. PMID- 29006829 TI - A Case for Diagnosis. PMID- 29006830 TI - Treatment of Scorpion Sting. PMID- 29006831 TI - Exercises on the Ground without Troops and Their Uses to Senior Medical Officers. PMID- 29006832 TI - Note to Aid the Search for Schistosomiasis in India. PMID- 29006833 TI - Mr. Montagu on the I. M. S. PMID- 29006834 TI - Editorship, I. M. Gazette. PMID- 29006835 TI - Report on Kala-Azar Cases Treated in the Mitford Hospital during 1918. PMID- 29006836 TI - Correspondence. PMID- 29006838 TI - Service Notes. PMID- 29006837 TI - The Bacteriology of "Spanish Influenza". PMID- 29006840 TI - Reports. PMID- 29006839 TI - Current Topics. PMID- 29006841 TI - Supplementary Report on Treatment of Lepers with Gynecardate of Soda "A". PMID- 29006842 TI - I. M. S. Pay Rates. PMID- 29006843 TI - An Unusual Case of Hydrophobia. PMID- 29006844 TI - A Simple Operation for Piles. PMID- 29006845 TI - "Rakta-Pittya" (Blood-Bile) of Ayurved. PMID- 29006846 TI - Results of Microscopic Examination of the Stools of Five Hundred East African Natives Not Suffering from Intestinal Diseases. PMID- 29006847 TI - Cerebro-Spinal Meningitis. PMID- 29006848 TI - Vegetable and Scurvy. PMID- 29006849 TI - Further Experience of Sodium Hydnocarpate (Sodium Gynocardate A) and a Trial of Sodium Morrhuate in Leprosy. PMID- 29006850 TI - Service Notes. PMID- 29006851 TI - The Mayo Native Hospital. PMID- 29006852 TI - Tendon Transplantation and Fixation for Nerve Injuries. PMID- 29006854 TI - Two Cases of Poisoning-Antifebrin and Naphthalene. PMID- 29006853 TI - A Case Resembling Yaws. PMID- 29006855 TI - Six Months' Accumulated Privilege Leave. PMID- 29006856 TI - Current Topics. PMID- 29006857 TI - Sir Pardey Lukis Memorial Scholarship. PMID- 29006859 TI - Sir Walter Buchanan, I.M.S., and "The Indian Medical Gazette". PMID- 29006858 TI - Radical Cure of Hydrocele by Plication. PMID- 29006860 TI - Tetanus with Facial Paralysis. PMID- 29006861 TI - Massive Anaesthesia. PMID- 29006862 TI - Bills of Mortality. PMID- 29006863 TI - On the Radical Cure of Inguinal Hernia: A Plea for Greater Simplicity. PMID- 29006864 TI - Further Investigations on the Chemical Nature of Margosic Acids (Fatty Acids of the Nim or Margosa Oil). Recent Conclusions Drawn from Experimental and Clinical Use of Margosates and Ethyl Ester Margosic. PMID- 29006865 TI - Santonine in Cholera Infantum. PMID- 29006866 TI - Surgical Notes. PMID- 29006867 TI - Early Treatment of Mental Diseases. PMID- 29006868 TI - Unique Case of Elephantiasis in the Female. PMID- 29006870 TI - Treatment of Beriberi. PMID- 29006869 TI - Fish Poisoning in the Persian Gulf. PMID- 29006871 TI - The Wassermann Reaction in Syphilis as a Guide to Treatment. PMID- 29006872 TI - Dr. Charles Lloyd. PMID- 29006873 TI - Ileal Stasis and Ulcer of the Stomach. PMID- 29006874 TI - Calculi of the Urinary Tract as Seen in a British General Hospital in India. PMID- 29006875 TI - Tetanus. PMID- 29006876 TI - Surgical Treatment of Tubercular Abscesses. PMID- 29006877 TI - Notes of Leprosy Cases Treated by Subcutaneous and Intravenous Injections of Sodium Morrhuate. PMID- 29006880 TI - War and Insanity. PMID- 29006879 TI - A Case of Viper Poisoning. PMID- 29006881 TI - The History of Influenza. PMID- 29006882 TI - Current Topics. PMID- 29006884 TI - Service Notes. PMID- 29006883 TI - Ophthalmological Congress. PMID- 29006885 TI - Gastrectasis and Gastro-Duodenal Ulceration. PMID- 29006887 TI - Hermaphroditism. PMID- 29006886 TI - Cholera Prophylactic Vaccination. PMID- 29006888 TI - Current Topics. PMID- 29006889 TI - Influenza. PMID- 29006890 TI - Second Attack of Eclampsia. PMID- 29006891 TI - A Case of Intra-Peritoneal Abscess. PMID- 29006892 TI - A Case of Malignant Tertian. PMID- 29006893 TI - Wasserman Technique. PMID- 29006894 TI - Indigenous Drugs. PMID- 29006895 TI - Acidosis in Relation to Diabetes. PMID- 29006896 TI - Railway Travelling in Hot Weather. PMID- 29006897 TI - Some Reminiscences. PMID- 29006898 TI - The Bacteriology of the Blood and the Treatment of Influenza. PMID- 29006899 TI - Medical Society. PMID- 29006900 TI - Service Notes. PMID- 29006901 TI - Intestinal Colic. PMID- 29006902 TI - Tetanus. PMID- 29006903 TI - Kala-Azar in Assam. PMID- 29006904 TI - The Treatment of Influenza in India. PMID- 29006905 TI - Ayurveda of To-Day. PMID- 29006906 TI - The Indications for Gastro-Jejunostomy. PMID- 29006907 TI - A Cold in the Head Cure. PMID- 29006908 TI - Green Vision after Quinine. PMID- 29006910 TI - Calcutta Tropical School. PMID- 29006909 TI - A Dog-Bite Treatment. PMID- 29006911 TI - Treatment of Malaria. PMID- 29006913 TI - Observations at Some Hospitals at Home. PMID- 29006912 TI - Influence of Atmospheric Temperature on Sandfly Fever. PMID- 29006915 TI - Service and War Notes. PMID- 29006914 TI - A New View of Rats and Plague. PMID- 29006917 TI - Current Topics. PMID- 29006916 TI - At the Clinic of Lietu.-Col. Henry Smith, Amritsar. PMID- 29006918 TI - Auto Therapy. PMID- 29006919 TI - An Interesting Sequela in a Case of Cholera. PMID- 29006920 TI - Is There a Primary Lesion in Leprosy? PMID- 29006921 TI - The 50th Vol. of I. M. G. PMID- 29006923 TI - Surgn-Genl. G. F. A. Harris. PMID- 29006922 TI - Studies in Malaria: III. Summary and Conclusion. PMID- 29006924 TI - The New Military Family Pension Fund. PMID- 29006925 TI - Two Cases of Ruptured Bladder Recovery. PMID- 29006927 TI - Service and War Notes. PMID- 29006926 TI - Charges of Rape. PMID- 29006929 TI - Current Topics. PMID- 29006928 TI - Progress in the Treatment of Cataract in India. PMID- 29006930 TI - Studies in Malaria: Oral Quinine in Malaria. PMID- 29006931 TI - The Nomenclature of Disease. PMID- 29006932 TI - Further Work on the Treatment of Kala-Azar, with Special Reference to Leucocyte Increasing Methods, Spleen Tabloids and Alkalies. PMID- 29006933 TI - Concerning Inoculation against Plague and Pneumonia: Part II. The Study of Curative Methods. PMID- 29006934 TI - Simple or Grievous Hurt. PMID- 29006935 TI - Accelerated Promotion, the War and Study Leave. PMID- 29006936 TI - Studies in Malaria: Part III-Continued. PMID- 29006937 TI - Concerning Inoculation against Plague and Pneumonia. PMID- 29006938 TI - Co-Relation of the Ductless Glands and the Onset of Labour. PMID- 29006939 TI - Excision of the Upper Jaw for Sarcoma. PMID- 29006941 TI - Current Topics. PMID- 29006940 TI - Injections of Cyanide of Mercury. PMID- 29006942 TI - Service and War Notes. PMID- 29006943 TI - Date of Commission, I. M S. PMID- 29006944 TI - The Indian Hospitals at Brighton. PMID- 29006945 TI - Pyorrhoea Alveolaris and Its Treatment by Vaccine and Emetine. PMID- 29006946 TI - The Medical Services in 1914. PMID- 29006947 TI - On a Macrostoma Found in Human Intestinal Contents. PMID- 29006948 TI - Iodine in Vaccination. PMID- 29006949 TI - Plague and Rats. PMID- 29006950 TI - Spinal Anaesthesia. PMID- 29006952 TI - Service and War Notes. PMID- 29006951 TI - Wright's Vaccine Bottles for Keeping Hypodermic Solutions. PMID- 29006953 TI - Port Health Regulations, Bombay. PMID- 29006954 TI - A Case of Malingering. PMID- 29006955 TI - Forty-Four Pounds of Ascites Fluid. PMID- 29006956 TI - Sero-Diagnosis of Syphilis-III. PMID- 29006957 TI - Some Cases of Typhoid and Para-Typhoid. PMID- 29006958 TI - Some Experiences in the War. PMID- 29006959 TI - Operation of Shortening the Round Ligaments. PMID- 29006960 TI - Abnormal Labour Case. PMID- 29006961 TI - Acidosis and Oedema in Its Relation to Glaucoma. PMID- 29006962 TI - Interesting Cases. PMID- 29006963 TI - Review of a Year's Medico-Legal Work in the Calcutta Morgue, 1914: Including Comparative Figures for the Triennium 1912-14. PMID- 29006964 TI - A Second Caesarean Section. PMID- 29006966 TI - Pay of Military Assistant Surgeons. PMID- 29006965 TI - A Case of Extensive Emphysema. PMID- 29006968 TI - Current Topics. PMID- 29006967 TI - Haemorrhage from the Lateral Sinus. PMID- 29006969 TI - Oil of Dhup. PMID- 29006970 TI - Sub-Asst. Surgns.' Conference. PMID- 29006971 TI - Service and War Notes. PMID- 29006972 TI - The Sero-Diagnosis of Syphilis.-Notes II. PMID- 29006973 TI - Laboratory Work Done at Kurseong Hospital in 1913. PMID- 29006974 TI - Surgical Survey of the Casualties in Mesopotamia. PMID- 29006975 TI - Iodine and Vaccination. PMID- 29006977 TI - Heart Strain among Sepoys. PMID- 29006976 TI - Right Scrotal Faecal Fistula. PMID- 29006978 TI - Quinine and Arsenical Preparations in Kala-Azar. PMID- 29006980 TI - Studies in Malaria: Part III-Continued. PMID- 29006979 TI - The Significance of Arneth's Leucocyte Count. PMID- 29006981 TI - Guinea Worm Disease in India. PMID- 29006982 TI - Current Topics. PMID- 29006983 TI - Classification of Medical Schools. PMID- 29006984 TI - The Treatment of Ankylostomiasis, or Hookworm Disease. PMID- 29006985 TI - A Medico-Legal Suggestion. PMID- 29006986 TI - Intramuscular Injection of Quinine in Lobar Pneumonia. PMID- 29006987 TI - Placenta Praevia. PMID- 29006988 TI - Current Topics. PMID- 29006989 TI - Research Work in Madras. PMID- 29006990 TI - Shrapnel Wounds of the Knee-Joint. PMID- 29006991 TI - Notes on a Small Outbreak of Cerebro-Spinal Fever. PMID- 29006992 TI - Studies in Malaria: Salvarsan in Malaria. PMID- 29006993 TI - A Case of Chronic Intestinal Obstruction Due to Tuberculous Cicatricial Constrictions of the Jejunum. PMID- 29006994 TI - A Useful Splint for Compound Fractures of the Leg. PMID- 29006995 TI - Report and Statistics of the Cholera Epidemic in the Ahmednagar District for the Years 1912 and 1913. PMID- 29006997 TI - Service and War Notes. PMID- 29006996 TI - Foreign Body in Trachea. PMID- 29006998 TI - Service and War Notes. PMID- 29006999 TI - Report on an Unusual Case of "Siamese" Twins. PMID- 29007000 TI - Emetine during Pregnancy. PMID- 29007001 TI - Sir Robert Macara. PMID- 29007002 TI - Current Topics. PMID- 29007003 TI - Emetine in Cholera. PMID- 29007004 TI - Studies in Malaria : Part II. PMID- 29007005 TI - Scrotal Fistula. PMID- 29007006 TI - Intravenous Injection of Quinine. PMID- 29007008 TI - Port Health Regulations, Calcutta. PMID- 29007007 TI - Death after Salvarsan. PMID- 29007009 TI - Dysentery. PMID- 29007010 TI - Review of a Year's Medico-Legal Work in the Calcutta Morgue, 1913. PMID- 29007012 TI - The War and the Drug Supply. PMID- 29007011 TI - On a Five Flagellate Trichomonas (N. Sp.) Parasitic in Man. PMID- 29007013 TI - The Hospital Ship "Madras". PMID- 29007015 TI - Kedani River Fever in the Federated Malay States. PMID- 29007014 TI - A Case of Fish Poisoning. PMID- 29007016 TI - Oleum Ricini: Its Place in Surgery. PMID- 29007017 TI - Rats and Plague. PMID- 29007018 TI - Cataract Statistics. PMID- 29007019 TI - Beta Naphthol Poisoning. PMID- 29007021 TI - Objectionable Puffing. PMID- 29007020 TI - Casualties in the Persian Gulf. PMID- 29007022 TI - A Case of Asphyxia. PMID- 29007023 TI - Current Topics. PMID- 29007024 TI - Jats and Scabies. PMID- 29007025 TI - Gunshot Wound: Peculiar Symptoms of Shock. PMID- 29007026 TI - Litholapaxy in India. PMID- 29007027 TI - Hypnotics and Their Uses. PMID- 29007028 TI - Retention of a Foreign Body for Twenty Years. PMID- 29007029 TI - Service and War Notes. PMID- 29007031 TI - Case of Bite from Naia Tripudians-Recovery. PMID- 29007030 TI - Studies in Malaria: III. The Injections of Quinine in Malaria. PMID- 29007032 TI - The Open Method of Treatment of Fractures. PMID- 29007034 TI - An Independent Medical College. PMID- 29007033 TI - Concerning Inoculation. PMID- 29007035 TI - Intestinal Parasites in the United Provinces. PMID- 29007036 TI - Hexamethylene Tetramine in Septic Inflammations of the Cornea and Conjunctiva. PMID- 29007038 TI - A Year's Surgery at the Secunderabad Civil Hospital. PMID- 29007037 TI - What Is a "Grievous Hurt?" PMID- 29007040 TI - Promotions in the I. M. S. PMID- 29007039 TI - "Morphine Injector's Septicaemia" ("Whitmore's Disease"). PMID- 29007042 TI - General Hospital, Madras. PMID- 29007043 TI - Surgical Notes from Madras Hospital. PMID- 29007041 TI - Results of the Treatment of 69 Cases of Cholera by Rogers' Method. PMID- 29007044 TI - Cataract Statistics. PMID- 29007045 TI - An Outbreak of Anthrax. PMID- 29007046 TI - Progressive Muscular Dystrophy (Erb.). PMID- 29007047 TI - Substitutes for German Health Resorts. PMID- 29007048 TI - Service and War Notes. PMID- 29007049 TI - Tetanus and Use of Quinine Hypodermically. PMID- 29007050 TI - Florence's Reaction-A Neglected Test for Seminal Stains. PMID- 29007051 TI - A Case of Raynaud's Symmetrical Gangrene. PMID- 29007052 TI - Quinine in Malaria. PMID- 29007053 TI - A Pocket Electroscope. PMID- 29007054 TI - Current Topics. PMID- 29007055 TI - Saline Injection in Cholera. PMID- 29007056 TI - Service and War Notes. PMID- 29007057 TI - Outbreaks of Epidemic Dropsy in Moffassil. PMID- 29007058 TI - A New Method of Gastro-Enterostomy. PMID- 29007059 TI - The Indian Military Family Pension Funds. PMID- 29007060 TI - Some Cholera Experiences. PMID- 29007061 TI - A Case of Hydrophobia with Incubation of One Year. PMID- 29007063 TI - Service and War Notes. PMID- 29007062 TI - The Treatment of Kala-Azar. By Tartar Emetic Intravenously and Inunctions of Metallic Antimony. PMID- 29007064 TI - Current Topics. PMID- 29007065 TI - Tetanus and the Use of Quinine Hypodermically. PMID- 29007066 TI - Nine Stones in a Urinary Bladder. PMID- 29007067 TI - The St. John Ambulance Association. A Brief Historical Sketch. PMID- 29007068 TI - Report of the Lady Hardinge Hospital, Brockenhurst. PMID- 29007070 TI - Rupture of Normal Spleen. PMID- 29007069 TI - The Treatment of Kala-Azar with Tartar Emetic. PMID- 29007071 TI - Service and War Notes. PMID- 29007073 TI - Irrigation and Cataract: Analysis of 250 Cases. PMID- 29007072 TI - Anatomical Dissymmetry. PMID- 29007074 TI - The Medical Practitioners' Bill. PMID- 29007075 TI - Combined Vaccines. PMID- 29007076 TI - French Surgery. PMID- 29007078 TI - War Surgery. PMID- 29007077 TI - Examination of the Rectum. PMID- 29007079 TI - Tetanus and Quinine. PMID- 29007080 TI - Current Topics. PMID- 29007081 TI - Hydrocele without Operation. PMID- 29007082 TI - Vesical Calculus. PMID- 29007083 TI - Blackwater Fever. PMID- 29007084 TI - A Big Stone in Bladder. PMID- 29007086 TI - Malaria in the Punjab (Gill). PMID- 29007085 TI - Epidemic Dropsy (Cart): The Epidemic Dropsy at Nator during the Year 1906. PMID- 29007087 TI - Current Topics. PMID- 29007088 TI - A Preliminary Report on the Treatment of Kala-Azar with Intravenous Injection of Metallic Antimony. PMID- 29007089 TI - The Actual Cautery in Mental Derangement. PMID- 29007090 TI - Coolie Anaemia. PMID- 29007091 TI - Anaemia in Indian Coolies. PMID- 29007092 TI - Russell's Viper Bite. PMID- 29007093 TI - Kala-Azar. PMID- 29007094 TI - Service and War Notes. PMID- 29007095 TI - Medical Education in U. S. A. PMID- 29007096 TI - Primary Atheroma of the Pulmonary Artery. PMID- 29007097 TI - Snake-Bite in C. P. PMID- 29007098 TI - A New Cataract Operation. PMID- 29007099 TI - Polo Eye Accidents. PMID- 29007100 TI - Correspondence. PMID- 29007101 TI - The Volume of the Dead Space in Breathing. PMID- 29007102 TI - The Use of Clamps in Restraining Haemorrhage during the Operation for Elephantiasis of the Scrotum. PMID- 29007103 TI - Some Observations on the Infant Mortality in Khulna District. PMID- 29007105 TI - The Year 1921. PMID- 29007104 TI - A Case of Myiasis of the Frontal and Ethmoidal Sinuses and the Orbit. PMID- 29007106 TI - A Method of Securing Dressings to Operation Wounds. PMID- 29007107 TI - Notes on a Case of Venereal Papilloma. PMID- 29007108 TI - The Research Defence Society. PMID- 29007109 TI - Service Notes. PMID- 29007110 TI - Correspondence. PMID- 29007112 TI - Notes on Current Topics. PMID- 29007111 TI - A Barbaric Method of Circumcision Amongst Some of the Arab Tribes of Yemen. PMID- 29007113 TI - The Effect of the Control and Rationing of Rice on Beri-Beri. PMID- 29007115 TI - Correspondence. PMID- 29007114 TI - Preliminary Notes on the Use of Tincture of Iodine Intravenously. PMID- 29007116 TI - Correspondence. PMID- 29007117 TI - A Note on a Recent Outbreak of Influenza. PMID- 29007118 TI - A Case of Malignant Malaria of an Unusual Type. PMID- 29007119 TI - Correspondence. PMID- 29007120 TI - Suggestions to Increase the Utility of the Medical College Journals. PMID- 29007121 TI - Some Principles in the Prevention of Deformities in Joints. PMID- 29007122 TI - Preliminary Report of the X-Ray and Radium Protection Committee. PMID- 29007123 TI - Infantile Enlargement of the Liver. PMID- 29007124 TI - Cattle in the Prevention of Malaria. PMID- 29007125 TI - New General Anaesthetic. PMID- 29007126 TI - The Role of Meteorology in Malaria. PMID- 29007127 TI - Bacilluria : Another Unnamed Organism. PMID- 29007128 TI - A Further Note on the Results of Influenza Vaccine Inoculation. PMID- 29007129 TI - Some Rare Cases. PMID- 29007130 TI - A Direct Record Scotometer, for Investigating the Central Field of Vision. PMID- 29007131 TI - Service Notes. PMID- 29007132 TI - Notes on Current Topics. PMID- 29007133 TI - Correspondence. PMID- 29007134 TI - Endemic Goitre. PMID- 29007135 TI - Osmosis through the Skin. PMID- 29007136 TI - Chronic Dysenteric Peritonitis. PMID- 29007137 TI - A Remarkable Case of Infantile Paralysis. PMID- 29007138 TI - Successful Treatment of a Case of Scalding. PMID- 29007139 TI - A Case of Filarial Cyst on the Eye. PMID- 29007140 TI - Correspondence. PMID- 29007141 TI - The Present Position with Regard to the Treatment of Ankylostomiasis. PMID- 29007142 TI - Recent Work on Malaria. PMID- 29007143 TI - An Unusual Case of Abdominal Injury. PMID- 29007144 TI - Correspondence. PMID- 29007145 TI - The Spirochaete of Dengue. PMID- 29007146 TI - Glaucoma and Epidemic Dropsy. PMID- 29007148 TI - Service Notes. PMID- 29007147 TI - Notes on Filariasis, Elephantiasis and Allied Conditions. PMID- 29007149 TI - Correspondence. PMID- 29007150 TI - Blackwater Fever in Khondmals, Orissa. PMID- 29007151 TI - Recovery of Income Tax. PMID- 29007152 TI - A Case of Haemophilia. PMID- 29007153 TI - Four Years' Surgery in an Indian General Hospital in Mesopotamia. PMID- 29007154 TI - The Value of Sodium Morrhuate and Sodium Linate in Tuberculosis and Leprosy. PMID- 29007155 TI - Filarial Disease. PMID- 29007156 TI - Notes on Current Topics. PMID- 29007157 TI - The Cure of Hernia by Vaccine. PMID- 29007158 TI - A Plea for the More Frequent Use of Intravenous Medication with Special Reference to the Use of Iodine. PMID- 29007159 TI - Correspondence. PMID- 29007160 TI - Beri-Beri. PMID- 29007161 TI - Notes on Current Topics. PMID- 29007162 TI - Service Notes. PMID- 29007163 TI - A Case of Death from Hornet-Stings' Popularly Known as "Wasp-Bite". PMID- 29007164 TI - British Income Tax. PMID- 29007165 TI - Correspondence. PMID- 29007166 TI - A Case of Gangrene Due to Carbon Monoxide Poisoning. PMID- 29007167 TI - Eighth Annual Meeting of the Indian Science Congress Calcutta, 1921: Section of Medical Research. PMID- 29007169 TI - Industrial Medicine and Hygiene in Bengal. PMID- 29007168 TI - Chronic Lead Poisoning in the Printing Presses of Calcutta. PMID- 29007170 TI - A Modified Bassini Method for the Radical Cure of Hernia by Plication and Overlapping of Externus Obliquus Abdominis with Statistics of 72 Cases. PMID- 29007172 TI - The Dangers of Delay in Operating on Appendicitis in Children and Pregnant Women. PMID- 29007171 TI - A Remarkable Case of Natural Recovery of Gangrenous Gut in a Case of Strangulated Hernia. PMID- 29007174 TI - Malaria and the Lost Cities of Ceylon. PMID- 29007173 TI - Service Notes. PMID- 29007175 TI - Off-Hand Diagnosis of Cataract. PMID- 29007177 TI - Notes on Current Topics. PMID- 29007176 TI - Indian Science Congress: Eighth Annual Meeting, Calcutta, 1921. Section of Medical Research. PMID- 29007179 TI - Broncho-Moniliasis. PMID- 29007178 TI - Round Worm in Surgery. PMID- 29007180 TI - Correspondence. PMID- 29007182 TI - Belladonna Poisoning. PMID- 29007183 TI - Bilharzia in Mesopotamia. PMID- 29007181 TI - Bacillus Coli Pericarditis. PMID- 29007184 TI - Bi-Lateral Cerebellar Abscess. PMID- 29007185 TI - Correspondence. PMID- 29007186 TI - Injection for Piles. PMID- 29007187 TI - Phylacogen in Pleuro-Pneumonia. PMID- 29007188 TI - Extraction of Guinea-Worm. PMID- 29007189 TI - Notes on Current Topics. PMID- 29007190 TI - Novarsenobillon in Syphilitic Buboes. PMID- 29007191 TI - Psycho-Analysis. PMID- 29007192 TI - Intestinal Obstruction with Internal Haemorrhage. PMID- 29007193 TI - Snake-Swallowing in an Insane. PMID- 29007194 TI - Correspondence. PMID- 29007195 TI - The Calcutta School of Tropical Medicine. PMID- 29007196 TI - Rheumatic Adenitis. PMID- 29007197 TI - Is Quinine a Failure? PMID- 29007198 TI - Arsenical Dermatitis after "606". PMID- 29007199 TI - Service Notes. PMID- 29007200 TI - A Medico-Legal Reference. PMID- 29007202 TI - The Cause of Dysentery. PMID- 29007201 TI - The Cure of Hernia by Vaccine. PMID- 29007203 TI - A Wassermann Survey of the Inmates of the Ranchi European Lunatic Asylum. PMID- 29007204 TI - Advice to Patients. PMID- 29007205 TI - The Uses of Sodium Cacodylate. PMID- 29007206 TI - A Curious Case of Ascites. PMID- 29007208 TI - Notes on Current Topics. PMID- 29007207 TI - Service Notes. PMID- 29007209 TI - Auto-Haemic or Auto-Serum Therapy. PMID- 29007210 TI - Strange Migration of a Round Worm. PMID- 29007211 TI - The Incidence of Gingivitis among the Indian Troops. PMID- 29007212 TI - Observations on Malaria, Part II. PMID- 29007214 TI - Plague at Pyawbwe (Upper Burma). PMID- 29007213 TI - Transfusion of Blood. PMID- 29007215 TI - Blackwater Fever. PMID- 29007217 TI - Service Notes. PMID- 29007216 TI - A Case of Strangulation in a Child of 15 Months. PMID- 29007218 TI - Notes on Current Topics. PMID- 29007219 TI - The Erect Posture of Man. PMID- 29007221 TI - Enteroptosis and Dropped Kidney. A New Method of Treatment. PMID- 29007220 TI - Relapsing Fever at Meshed, North-East Persia. PMID- 29007222 TI - Correspondence. PMID- 29007224 TI - The Anal-Complex and Its Relation to Delusions of Persecution. PMID- 29007223 TI - Flavine in Ophthalmic Practice. PMID- 29007225 TI - A Unique Instance of Lead Intoxication. PMID- 29007226 TI - A Case of Encephalitis Lethargica. PMID- 29007227 TI - Correspondence. PMID- 29007228 TI - Correspondence. PMID- 29007229 TI - Influenza and Other Respiratory Infections. PMID- 29007230 TI - Septic Gastritis in Kashmir. PMID- 29007231 TI - Laboratory Records from Mesopotamia. PMID- 29007232 TI - Cataract Operations. PMID- 29007233 TI - Kala-Azar: Diagnosis and Treatment. PMID- 29007234 TI - Correspondence. PMID- 29007236 TI - Service Notes. PMID- 29007235 TI - Snake-Bite. PMID- 29007237 TI - Haemorrhagic Meningo-Encephalitis in Anthrax: Report of a Case. PMID- 29007239 TI - The Serdang Doktor Fonds: An Experiment in Practical Sanitation in Sumatra. PMID- 29007238 TI - Thymol in Uncinariasis. PMID- 29007242 TI - Correspondence. PMID- 29007240 TI - Notes on Current Topics. PMID- 29007241 TI - The Teaching of Midwifery in Indian Medical Colleges. PMID- 29007243 TI - Superacute Oedema of Lungs. PMID- 29007244 TI - The Formol-Gel Test in Kala-Azar. PMID- 29007246 TI - Iodine Injection for Septic Conditions. PMID- 29007245 TI - A Typhus-Like Fever in India, Possibly Transmitted by Ticks. PMID- 29007247 TI - Service Notes. PMID- 29007248 TI - The Cure of Hernia by Vaccine. PMID- 29007249 TI - Correspondence. PMID- 29007251 TI - The General Medical Council and Indian Medical Education. PMID- 29007250 TI - Sebaceous Horn. PMID- 29007252 TI - Notes on a Case of Liver Abscess Treated by Aspiration and Injection of Quinine Hydrochloride: Recovery. PMID- 29007254 TI - Kaolin Treatment of Cholera. PMID- 29007253 TI - Notes on the Twelve-Day Fever of Nigeria. PMID- 29007255 TI - The Annual Report of the Sanitary Commissioner with the Government of India for 1919. PMID- 29007256 TI - The Present Position of Leprosy in India. PMID- 29007258 TI - Notes on Current Topics. PMID- 29007257 TI - The Use of the Galvanic Current in the Treatment of Fibrous Ankylosis and Kindred Affections. PMID- 29007259 TI - Popular Health Instruction. PMID- 29007260 TI - A Successful Operation of Bilateral Tumours of the Abdomen. PMID- 29007261 TI - Correspondence. PMID- 29007262 TI - Correspondence. PMID- 29007264 TI - Correspondence. PMID- 29007263 TI - Correspondence. PMID- 29007266 TI - Notes on 2,412 Eye Operations Performed in a Month at Shikarpur, Sind, in January and February, 1921. PMID- 29007265 TI - Pathology of Ringworm and Allied Skin Diseases. PMID- 29007267 TI - The Poison of the Scolopendridae Being a Special Reference to the Andaman Species. PMID- 29007269 TI - Diet in Diabetes. PMID- 29007268 TI - Short Notes on Two Cases of Snake-Bite, Echis Carinata: Phoorsa. PMID- 29007270 TI - Correspondence. PMID- 29007272 TI - Notes on Current Topics. PMID- 29007271 TI - The Treatment of Malarial Fever in Individuals Susceptible to Attacks of Black Water Fever by Intravenous Injection of an Antihaemolytic Quinine Solution. PMID- 29007273 TI - The Practical Side of Cheap, Efficient Incineration. PMID- 29007274 TI - Some Interesting Eye Cases. PMID- 29007275 TI - The Treatment of Erysipelas. PMID- 29007276 TI - A Case of Herpes Zoster Ophthalmicus. PMID- 29007277 TI - Radical Cure of Hydrocele by Plication and Overlapping of Tunica Vaginalis with Statistics of 225 Cases. PMID- 29007278 TI - An Undiagnosed Case of Hepatic Enlargement. PMID- 29007279 TI - Correspondence. PMID- 29007280 TI - The Fight against Tuberculosis. PMID- 29007281 TI - Service Notes. PMID- 29007283 TI - Physiological Standardisation of Digitalis with Special Reference to the Method Suitable for Use in India. PMID- 29007282 TI - Statistics of the Treatment of Cholera. PMID- 29007284 TI - A Case of Cerebral Abscess. PMID- 29007286 TI - Notes on Current Topics. PMID- 29007285 TI - "Stibenyl" and Its Use in Kala-Azar. PMID- 29007287 TI - Relapsing Fever Epidemic in Seoni District (Central Provinces), February to May 1920. PMID- 29007289 TI - The Use of Calcium Chloride in Labour. PMID- 29007288 TI - An Interesting Case of Rabies. PMID- 29007290 TI - A Case of Full Term Pregnancy. PMID- 29007292 TI - Complete Extirpation of Pancreas with Absence of Glycosuria. PMID- 29007291 TI - The B. M. A. and the I. M. S. PMID- 29007293 TI - Report on Dr. Gokal Chand's Specimen. PMID- 29007294 TI - A Cyst of Interest. PMID- 29007295 TI - Haemolytic Test in Kala-Azar. PMID- 29007296 TI - Toxic Idiopathies. PMID- 29007297 TI - Cachar Sore and Its Treatment. PMID- 29007298 TI - Royapuram Medical School War Memorial. PMID- 29007300 TI - Service Notes. PMID- 29007299 TI - Permanganate Pills in Cholera. PMID- 29007301 TI - The British Medical Association and the I.M.S. PMID- 29007302 TI - A Double-Headed Monster. PMID- 29007303 TI - A Case of Ovarian Cyst of Unique Dimensions. PMID- 29007305 TI - Haemorrhagic Type of Malaria. PMID- 29007306 TI - Some Notes on Novarsenobillon. PMID- 29007304 TI - Treatment of Malaria with Quinine. PMID- 29007308 TI - A Medico-Legal Note of Importance: A Male Infant Born with Two Lower Central Incisor Teeth. PMID- 29007307 TI - A Case for Diagnosis: A Developmental Defect of Unknown Origin. PMID- 29007310 TI - Observations on Malaria. PMID- 29007309 TI - Two Vesical Calculi of Peculiar Shape. PMID- 29007311 TI - The Incubation Period of Leprosy. PMID- 29007313 TI - The Stability of "A. B." Insulin in the Tropics. PMID- 29007312 TI - A Practical Method of Preserving Chloride of Lime in India. PMID- 29007314 TI - The Technique of Intravenous Injections. PMID- 29007315 TI - Report on 69 Cases of Non-Venereal Ulcers Treated by Intravenous Injection of a Solution of Tartar Emetic. PMID- 29007316 TI - The Preparation of Permanent Stained Microscopical Specimens of Erythrocytes from Old Blood Stains. PMID- 29007317 TI - Erratum: The Indian Medical Year, 1923. A Correction. AB - [This corrects the article on p. 35 in vol. 59.]. PMID- 29007318 TI - A Short Note on an Outbreak of Three-Day Fever in Patna. PMID- 29007320 TI - The Treatment of Small-Pox. PMID- 29007319 TI - Nerve Abscess in Leprosy. PMID- 29007321 TI - Report on the Treatment of Gonorrhoea by Intravenous Injections of Acriflavine. PMID- 29007322 TI - Intestinal Coleoptera. PMID- 29007323 TI - The Typhus Group of Fevers. PMID- 29007324 TI - A Case of Alastrim (Kaffir Pox). PMID- 29007325 TI - Gold Chloride in Snake-Bite. PMID- 29007326 TI - The Geographical Distribution of Kala-Azar. PMID- 29007327 TI - A Case of Epithelioma of the Penis. PMID- 29007329 TI - India in a State of Grave Emergency. PMID- 29007328 TI - The Hospital Working Day. PMID- 29007330 TI - Service Notes. PMID- 29007331 TI - A Simple Method of Staining Leishmania Donovani in Tissues. PMID- 29007332 TI - Psycho-Therapy in General Practice. PMID- 29007333 TI - Notes on Current Topics. PMID- 29007334 TI - Intravenous Iodine. PMID- 29007335 TI - Ascites as a Complication in Diabetes. PMID- 29007336 TI - Electrolysis in Trichiasis. With or without Entropion. PMID- 29007337 TI - Sensitized Anti-Plague Vaccine. PMID- 29007338 TI - A Case of Double Hernia. PMID- 29007339 TI - A Fibroma of the Orbital Fossa. PMID- 29007340 TI - On the Dysenteries of India. PMID- 29007341 TI - Some Observations on the Toxicity of Emetine. PMID- 29007342 TI - Intravenous Iodine Injections in Plague. PMID- 29007343 TI - Notes on the Reorganisation of the Field Ambulance for Work on the Indian Frontier, with Suggestions for Improvements in Equipment and Training. PMID- 29007344 TI - Correction. AB - [This corrects the article on p. 200 in vol. 59.]. PMID- 29007345 TI - Insulin in the Tropics. PMID- 29007347 TI - Service Notes. PMID- 29007346 TI - Squamous Celled Epithelioma Due to Kangri Burn. PMID- 29007348 TI - Zinc Ionisation in Eczema of the Auditory Canal. PMID- 29007349 TI - An Unusual Case of Rupture of an Aortic Aneurysm. PMID- 29007350 TI - A Suit for Professional Fees. PMID- 29007351 TI - Erratum: Notes on the Treatment of Malaria with the Alkaloids of Cinchona. AB - [This corrects the article on p. 153b in vol. 59.]. PMID- 29007352 TI - Phenolaine. PMID- 29007353 TI - The Variability in Rabbits Used for the Assay of Insulin. PMID- 29007354 TI - Scarlatina in Indians. PMID- 29007355 TI - On the Seven Scourges of India. PMID- 29007356 TI - An Unusual Condylomatous Tumour of the Lip. PMID- 29007357 TI - A Case of Renal Glycosuria. PMID- 29007358 TI - Notes on Current Topics. PMID- 29007359 TI - Insulin in the Tropics. PMID- 29007361 TI - The Indian Medical Year. PMID- 29007360 TI - A Note on the Serological Diagnosis of Typhus by the Weil-Felix Reaction. PMID- 29007362 TI - A Case of Lymphatic Cyst or Hydrocele of the Neck. PMID- 29007364 TI - Service Notes. PMID- 29007363 TI - The Treatment of Syphilis by "Bismuth". PMID- 29007366 TI - The Next Step. PMID- 29007365 TI - The Deterioration of Insulin in India. PMID- 29007367 TI - On a Pseudo-Organism in the Blood in Dengue. PMID- 29007369 TI - Malaria in Assam. PMID- 29007368 TI - A Cystic Tumour of the Omentum. PMID- 29007370 TI - Two Surgical Cases. PMID- 29007371 TI - Venereal Disease Problems among Indian Women. PMID- 29007372 TI - Rhinoliths. PMID- 29007373 TI - Plasmodium Tenue and P. Ovale. PMID- 29007375 TI - Service Notes. PMID- 29007374 TI - A Case of Pancreatic Cyst in a Child. PMID- 29007376 TI - A. B. Insulin Batch, No. 243. PMID- 29007377 TI - A Case of a Perforating Injury of the Eye from a Foreign Body, at the Clinic of Wiedenkrankenhaus, Vienna. PMID- 29007378 TI - Ascaris Lumbricoides and Severe Haemorrhage as Complications in a Case of Mixed Type of Dysentery. PMID- 29007379 TI - Notes on Current Topics. PMID- 29007380 TI - Preliminary Notes on the Use of a Sensitised Anti-Plague Vaccine. PMID- 29007381 TI - The Dosage of Sodium Cacodylate Intravenously. PMID- 29007382 TI - Liver Function Tests and Carbon Tetrachloride. PMID- 29007384 TI - The Other Side of the Picture. PMID- 29007383 TI - Erratum: The Indian Medical Year, 1923. A Correction. AB - [This corrects the article on p. 35 in vol. 59.]. PMID- 29007385 TI - On the Failure of Vitex Peduncularis in the Treatment of Malaria. PMID- 29007386 TI - Insulin in the Tropics. PMID- 29007388 TI - A Sensitized Anti-Plague Vaccine. PMID- 29007387 TI - On the Potency of Insulin in the Tropics. PMID- 29007389 TI - Some Common Ailments of Children, Their Identification and Treatment. PMID- 29007390 TI - Notes on Malaria in Shillong. PMID- 29007391 TI - The Deterioration of Insulin in India: An Experiment of 6 Months' Duration, with One Batch of British Insulin, Now 8 Months Old, to Illustrate Its Extent of Deterioration. PMID- 29007393 TI - Insulin. PMID- 29007392 TI - Testing of Insulin. PMID- 29007394 TI - Malaria on Ambootia Tea Estate near Kurseong and the Success of Some Anti Malarial Operations. PMID- 29007396 TI - The Use of Intravenous Injections of Iodine in the Treatment of Septicaemia and Other Septic Conditions. PMID- 29007395 TI - A Case of Abdominal Injury Treated by Resection and Enterorrhaphy. PMID- 29007397 TI - Obstetric Teaching. The Live Method. PMID- 29007398 TI - Corrigendum. AB - [This corrects the article on p. iii in vol. 58.]. PMID- 29007400 TI - Service Notes. PMID- 29007399 TI - A Case of Paratyphoid B. PMID- 29007401 TI - The Rockefeller Foundation. PMID- 29007402 TI - What Disease Costs India: Being a Statement of the Problem before Medical Research in India. PMID- 29007403 TI - Notes on the AEtiology of Some Skin Diseases Met with in the Tropics. PMID- 29007404 TI - The British Empire Exhibition. PMID- 29007405 TI - Poisonous Wheat. PMID- 29007406 TI - The Deterioration of Insulin in India. PMID- 29007407 TI - On a Standard Treatment for Malaria. PMID- 29007408 TI - A Case of Anaphylaxis. PMID- 29007409 TI - An Outbreak of the Epidemic Dropsy Form of Beriberi in Calcutta. PMID- 29007410 TI - Benger's Food. PMID- 29007412 TI - Notes on a Year's Work (1923) at the U. F. C. Mission Hospital, Kalna, Burdwan District. PMID- 29007411 TI - A Case of Local Tetanus. PMID- 29007413 TI - The Operation of Litholapaxy and Its Limitations. PMID- 29007414 TI - The Formol-Gel (Aldehyde) Test as a Means of Diagnosis of Kala-Azar. PMID- 29007416 TI - Notes on Current Topics. PMID- 29007415 TI - Some Further Observations in Respect to Syphilis Complicating Mental Disease. PMID- 29007417 TI - Insulin in the Tropics. PMID- 29007418 TI - Syphilitic Granulomata of the Uterus and Appendages in a Child of 8 Years. PMID- 29007419 TI - Clitoria Ternatea in Leucoderma. PMID- 29007421 TI - On a Non-Operative Treatment for Hernia. PMID- 29007420 TI - The Leprosy Problem. PMID- 29007422 TI - On the Results of Anti-Malaria Measures in Five Towns in the United Provinces. PMID- 29007423 TI - The British Empire Exhibition. PMID- 29007424 TI - Some Factors in Individual Susceptibility. PMID- 29007425 TI - Intravenous Iodine in Plague. PMID- 29007426 TI - Dental Surgery for Medical Practitioners. PMID- 29007427 TI - An Automatic Fly Proof Latrine Seat. PMID- 29007428 TI - Intravenous Air Embolism. PMID- 29007429 TI - Notes on Current Topics. PMID- 29007430 TI - Clinical Notes on Some Interesting Cases of Difficult Labour. PMID- 29007431 TI - On the Use of Adrenalin in White Asphyxia of the Newly Born. PMID- 29007432 TI - The Provision of Whole Time District Health Personnel in the United Provinces. PMID- 29007433 TI - The Effect of Enteric Vaccine on Endemic Goitre in Children. PMID- 29007434 TI - On Transient Infections with Leishmania Donovani in Man and Animals. PMID- 29007435 TI - Some Experiments on the Injuries Produced by Firearms at Short Range. PMID- 29007437 TI - British Income-Tax Refunds. PMID- 29007436 TI - On a New Treatment for Tuberculosis. PMID- 29007438 TI - Supernumerary Spleen with Notes on a Case of a Rare Type. PMID- 29007440 TI - Intestinal Coleoptera. PMID- 29007439 TI - Is Leprosy Curable? PMID- 29007442 TI - Service Notes. PMID- 29007441 TI - Butyn as a Local Anaesthetic in Ophthalmic Surgery. PMID- 29007443 TI - A Strangulated Diaphragmatic Hernia of the Stomach. PMID- 29007445 TI - Service Notes. PMID- 29007444 TI - Typhus Fever in the Agency Tracts, Madras Presidency. PMID- 29007446 TI - A Case of Snake-Bite (Echis Carinatus) Treated with Hypertonic Saline Solution Intravenously. PMID- 29007447 TI - The Treatment of Puerperal Tetanus. PMID- 29007448 TI - An Unusual Case of Spinal Syphilis. PMID- 29007449 TI - The Dysenteries of India. PMID- 29007450 TI - The Spontaneous Absorption of Amoebic Abscess of the Liver under Emetine Therapy. PMID- 29007451 TI - A Case of Atresia of the Vagina and Uterus. PMID- 29007452 TI - Marris' Atropine Test in Typhoid Fever and Its Value. PMID- 29007453 TI - The Problem of Cure in Kala-Azar. PMID- 29007455 TI - Report on the Surgical Work at the Madras Government General Hospital, 1923. PMID- 29007454 TI - Malarial Infection as a Possible Cause of Raynaud's Disease. PMID- 29007456 TI - Saponification of Bodies in the United Provinces of Agra and Oudh: Being a Paper Read at the Medical Research Section of the Indian Science Congress, 1924. PMID- 29007457 TI - A Pseudo-Addisonian Syndrome. PMID- 29007459 TI - Methods of Treatment in Cholera. PMID- 29007458 TI - The Kala-Azar Transmission Problem. PMID- 29007461 TI - Intravenous Air Embolism. PMID- 29007460 TI - Of Fashions in Medicine. PMID- 29007462 TI - A Case of Hydroa Gravidarum. PMID- 29007463 TI - A Case of Esophoria after Typhoid Fever. PMID- 29007464 TI - First Progress Report of the Campaign against Mosquitoes, Back Bay Reclamation Scheme, Bombay: Reviewing the Origin and Progress of the Anti-Malarial Campaign, during the Period June 1923 to June 1924. PMID- 29007465 TI - Mastoid Suppuration without Tympanic Perforation and Suppuration. PMID- 29007466 TI - On Spider-Lick, a Dermatozoosis. PMID- 29007467 TI - Intravenous Iodine. PMID- 29007468 TI - A Case of Stone in the Bladder with Prolapse of the Rectum. PMID- 29007470 TI - The Treatment of Cholera by Cresol. PMID- 29007469 TI - Some Interesting Eye Cases. PMID- 29007471 TI - Fifteen Cases of Exanthematic Typhus in Calcutta. PMID- 29007472 TI - A Case of Missed Labour. PMID- 29007473 TI - The Globulin Content of the Serum in Kala-Azar. PMID- 29007474 TI - An Extreme Case of Morphia Tolerance. PMID- 29007476 TI - Service Notes. PMID- 29007475 TI - A Large Monolocular Ovarian Cyst. PMID- 29007477 TI - A Simple Method for Detecting and Estimating Indican in the Urine by Means of the Cotton-Wool Plug Test. PMID- 29007478 TI - The Use of the Seton in Kala-Azar. PMID- 29007479 TI - A Case of Gangosa in Baluchistan. PMID- 29007480 TI - Beriberi and Rice Control in Malaya. PMID- 29007481 TI - Why Are We One-Handed. PMID- 29007482 TI - A Case of Complete Traumatic Dislocation of the Lens under the Conjunctiva. PMID- 29007484 TI - Hereditary Glaucoma Affecting Three Generations. PMID- 29007483 TI - A Case of the Tetany of Pregnancy. PMID- 29007485 TI - Intestinal Stasis and Cancer in Indians. PMID- 29007486 TI - Urea-Stibamine in the Treatment of Kala-Azar under Tea Garden Conditions. PMID- 29007487 TI - A Case of Aneurysm of the External Carotid Artery. PMID- 29007488 TI - Ante-Natal Care: An Address on "The New Midwifery" at the All-India Baby Week Conference in Calcutta. PMID- 29007490 TI - A Congenital Abnormality of the Uterus and Vagina. PMID- 29007489 TI - Experimental Studies in Bilharzia Therapy (S. Spindalis): A Preliminary Report. PMID- 29007491 TI - A Case of Uterine Fibroid. PMID- 29007492 TI - A Case of Rudimentary Uterus in an Adult Female. PMID- 29007494 TI - Studies in Dracontiasis: Part VI. PMID- 29007493 TI - Notes on the Local Concentration of Drugs. PMID- 29007496 TI - A Case of Carcinoma of the Urethra in a Youth. PMID- 29007497 TI - Dustypore. PMID- 29007495 TI - Pyorrhoea Alveolaris. PMID- 29007498 TI - The Diagnosis of Kala-Azar by Examination of Thick Blood Films. PMID- 29007499 TI - The Use of Emetine Intravenously. PMID- 29007500 TI - Encysted Guinea-Worm of the Orbit. PMID- 29007501 TI - A Case of Double Malarial Infection, Complicated with Typhoid Fever in a Patient Six Months' Pregnant. PMID- 29007502 TI - Foreign Bodies in the Ear and Nose. PMID- 29007503 TI - Four Cases of Spotted Fever at Nagpur. PMID- 29007504 TI - A Unique Case of Hydatid of the Liver. PMID- 29007505 TI - A New Device for Ionization of the Urethra. PMID- 29007506 TI - Corrigendum. AB - [This corrects the article on p. 304 in vol. 59.]. PMID- 29007507 TI - Ophthalmological Jottings from a Leave Diary. PMID- 29007508 TI - Two Cases of Pseudo-Hermaphrodism Admitted to the Myingyan Central Jail, Burma. PMID- 29007509 TI - Of Entamoeba Histolytica Carriers. PMID- 29007511 TI - An Unusual Number of Intussusceptions. PMID- 29007510 TI - The Psychology of Freud. PMID- 29007512 TI - A Case of Abdominal Injury. PMID- 29007513 TI - Service Notes. PMID- 29007514 TI - The Psychology of Freud. PMID- 29007515 TI - The Medical Aspects of the Indian Census of 1921. PMID- 29007516 TI - Cases of Kala-Azar Showing Little or No Improvement with Sodium Antimony Tartrate, Subsequently Cured by Urea Stibamine. PMID- 29007517 TI - A Note on the Cause of Pemphigus Contagiosus (Manson). PMID- 29007518 TI - Gangosa in India. PMID- 29007520 TI - Notes on Current Topics. PMID- 29007519 TI - Notes on Malaria in Hill-Stations in or near the Eastern Himalayas. PMID- 29007521 TI - Some Observations on the Cholera Epidemic in Bombay, 1923. PMID- 29007522 TI - The Aldehyde Test in Schistosomum Haematobium Infection. PMID- 29007523 TI - A Case of Rupture of the Retina. PMID- 29007524 TI - Notes on a Few Cases of Cholera Treated by Various Methods of Treatment. PMID- 29007525 TI - Why Are We Right Handed. PMID- 29007526 TI - Pneumonia, Its Complications and Treatment. PMID- 29007527 TI - A Note upon Routine Blood Cultures. PMID- 29007528 TI - The Future of Medicine in India. PMID- 29007529 TI - The Use of Intravenous Iodine in Pyaemia. PMID- 29007530 TI - A Severe Case of Syphilis. PMID- 29007531 TI - On the Importance of Keeping Cool. PMID- 29007532 TI - A Preliminary Note on the Pharmacological Action and Therapeutic Properties of Kuth Root-Saussurea Lappa. PMID- 29007533 TI - Animals as Disseminators of Hookworm Eggs and Larvae. PMID- 29007534 TI - Indian Santonin: Extracted from the Indian Species of Artemisia Maritima. PMID- 29007536 TI - A Case of Acquired Ventral Hernia. PMID- 29007535 TI - The Use of Emetine Intravenously. PMID- 29007537 TI - Antigalactism. PMID- 29007538 TI - Morphia Tolerance. PMID- 29007539 TI - A Case for Diagnosis. PMID- 29007541 TI - The Relative Value of Diagnostic Methods, and Evidence of Cure in Kala-Azar. PMID- 29007540 TI - Morphia Tolerance. PMID- 29007542 TI - Sulfarsenol in Rat-Bite Fever. PMID- 29007544 TI - Service Notes. PMID- 29007543 TI - Surgical Sundries. PMID- 29007545 TI - The Therapeutic Value of Intravenous Iodine. PMID- 29007546 TI - A Case of Imperforate Anus. PMID- 29007547 TI - Local Tetanus. PMID- 29007548 TI - An Epidemic Disease in Bombay. PMID- 29007550 TI - A Fish Bone in the Laryngo-Pharynx. PMID- 29007549 TI - Ankylosis of Joints. PMID- 29007551 TI - A Case of Complete Transposision of the Viscera. PMID- 29007552 TI - The Treatment of Habituation to Morphia. PMID- 29007553 TI - A Standard Treatment for Malaria. PMID- 29007554 TI - A Note on the Testing of Insulin in India. PMID- 29007556 TI - Reaction after Intravenous Injection of Antimony, and Its Control by the Use of Normal Saline for the Solution. PMID- 29007555 TI - On the Life History of Herpetomonas Muscae Domasticae: A Preliminary Note. PMID- 29007557 TI - Corrigendum. AB - [This corrects the article on p. 463a in vol. 59.]. PMID- 29007559 TI - Some Experiments for the Solution of the Rural Health Problem of India. PMID- 29007558 TI - A "Treatment" for Prolapsus Uteri. PMID- 29007561 TI - A Summary of Recent Work on Lobar Pneumonia. PMID- 29007560 TI - Service Notes. PMID- 29007562 TI - Notes on Current Topics. PMID- 29007563 TI - On a Herpetomonas Found in the Gut of the Sandfly, Phlebotomus Argentipes, Fed On Kala-Azar Patients: A Preliminary Note. PMID- 29007564 TI - Canine Leishmaniasis in Bombay. PMID- 29007565 TI - Some Uses of "E. C." in Hospital Work. PMID- 29007566 TI - The Venereal Disease Problem in India. PMID- 29007567 TI - Medical Relief in Rural Areas. PMID- 29007568 TI - Corrigendum. AB - [This corrects the article on p. 588b in vol. 59.]. PMID- 29007569 TI - A Comment on the Report on Maternal Mortality during Childbirth in England by Dr. J. Campbell of the Ministry of Health with a Reference to Maternal Mortality in India. PMID- 29007570 TI - Notes on Some Cases of Relapsing Fever. PMID- 29007571 TI - Intestinal Coleoptera. PMID- 29007572 TI - Service Notes. PMID- 29007573 TI - Clinical Notes on Some Interesting Cases of Difficult Labour. PMID- 29007574 TI - Notes on the Treatment of Oriental Sore by Intravenous Injections of Antimony Tartrate. PMID- 29007575 TI - On the Results of Anti-Malaria Measures in Five Towns in the United Provinces: Part I. PMID- 29007576 TI - Foreign Bodies in the Ear and Nose. PMID- 29007577 TI - Intraperitoneal Injection of Anti-Sera. PMID- 29007578 TI - Internal Version in a Case of Flattened Pelvis. PMID- 29007579 TI - A Day in the Shikarpur Eye Clinic. PMID- 29007580 TI - Observations on OEdema. PMID- 29007581 TI - A Case of Chloroform Poisoning by the Oral Route. PMID- 29007582 TI - A Case of Exfoliative Dermatitis after Novoarsenobillon Injections. PMID- 29007583 TI - Medical Education in India. PMID- 29007585 TI - A Further Note on the Efficacy of the Essential Oils in the Prevention and Treatment of Cholera. PMID- 29007584 TI - The Typhus Group of Fevers. PMID- 29007586 TI - Chronic Dysenteric Peritonitis as the Probable Cause of a Common Form of Ascites in the Tropics. PMID- 29007588 TI - Notes on Current Topics. PMID- 29007587 TI - Erratum: The Tropical Diseases' Bureau: A Correction. AB - [This corrects the article on p. 49 in vol. 59.]. PMID- 29007589 TI - A Case of Hypersensitiveness to Horse Serum with Successful Treatment by De Sensitization. PMID- 29007590 TI - The Use of Petrol for Cleansing the Skin Prior to Operating. PMID- 29007591 TI - Hookworm Dissemination. PMID- 29007592 TI - A Fatal Case of Poisoning by Neo-Kharsivan. PMID- 29007594 TI - The "Crescent" Dissecting Microscope. PMID- 29007593 TI - Insulin in the Tropics. PMID- 29007596 TI - Note on Hectine and Hectargyre. PMID- 29007595 TI - A Note on the Value of Prophylactic Inoculation in the Prevention of Chronic Carriers of Typhoid and Paratyphoid Bacilli. PMID- 29007597 TI - A Case of Multiple Chondromata. PMID- 29007599 TI - Notes on Current Topics. PMID- 29007598 TI - The Director-Generalship, I. M. S. PMID- 29007600 TI - Pneumonia-A Short Note. PMID- 29007601 TI - Caesarian Section for Dystocia Due to Osteomalacia. PMID- 29007602 TI - Service and War Notes. PMID- 29007603 TI - Medical Diseases of the War. PMID- 29007604 TI - The Use of Heroin. PMID- 29007605 TI - Abdominal Surgery: Notes and Observations on the Operative Work of the Miraj Hospital for the Year, 1915, Including Some More Recent Cases. PMID- 29007606 TI - Notes on a Case of Hernia (With Obstruction) into the Lesser Sac of the Peritoneum. PMID- 29007607 TI - Injuries in the Region of the Elbow and Their Treatment. PMID- 29007608 TI - Use of Palmyra Fibre. PMID- 29007609 TI - Bombay Medical Registration Act. PMID- 29007610 TI - Necrosis, and Strong Solutions of Quinine. PMID- 29007611 TI - Service and War Notes. PMID- 29007612 TI - Ophthalmic Notes. PMID- 29007613 TI - Anomalous Kala-Azar. PMID- 29007614 TI - Snake Bites. PMID- 29007615 TI - Ulcerating Granuloma. PMID- 29007616 TI - Use of Tuberculin. PMID- 29007617 TI - Helminthiasis among Prisoners. PMID- 29007619 TI - A Venomous Bite. PMID- 29007618 TI - Multiple Abscess in the Brain: With Pathological Report. PMID- 29007620 TI - Epidemic of Jaundice, Waziristan Field Force. PMID- 29007621 TI - Frontier Sores. PMID- 29007622 TI - Diabetes. PMID- 29007623 TI - Vaccination on E. I. Ry. PMID- 29007624 TI - Tucktoo Bite. PMID- 29007625 TI - Globulins in Kala-Azar. PMID- 29007626 TI - Notes on Current Topics. PMID- 29007627 TI - Position of a Bearer Division or Subdivision during a Rear-Guard Action. PMID- 29007628 TI - Pernicious Malignant Tertian Malaria Successfully Treated by Quinine Acid Hydrobromide Intravenously and the Failure of "Splenox" in Benign Tertian Malaria. PMID- 29007629 TI - Six Months' Surgical Nursing. PMID- 29007630 TI - A Fish in the Left Bronchus. PMID- 29007631 TI - The After-Treatment of Cataract Extraction by Shield Instead of Dressing and Bandage. PMID- 29007632 TI - Probable Causes of Fever in the Waziristan Field Force. PMID- 29007633 TI - Death from Rupture of the Spleen Twenty-Five Days after Abdominal Injuries and Apparent Recovery. PMID- 29007634 TI - The Rationing of Patients. PMID- 29007635 TI - The "New Operation for Cataract". PMID- 29007636 TI - Quinine Hypodermically. PMID- 29007638 TI - Current Topics. PMID- 29007637 TI - Note on a Case of Ainhum. PMID- 29007639 TI - Guinea Worm and Iodine. PMID- 29007640 TI - Medical Society. PMID- 29007641 TI - India and Medical Progress. PMID- 29007643 TI - Service and War Notes. PMID- 29007642 TI - Cowhorn in the Abdomen. PMID- 29007644 TI - Some New Inventions. PMID- 29007645 TI - The Dressings of Surgical Cases. PMID- 29007646 TI - Maximal Perchloride Irrigation of the Conjunctiva in Cataract Operations. PMID- 29007647 TI - Bengali School Boys' Health Examination. PMID- 29007648 TI - A Note on "Chandu". PMID- 29007651 TI - Service and War Notes. PMID- 29007650 TI - Hookworm Infection in India. PMID- 29007649 TI - Autotherapy. PMID- 29007652 TI - Medical Aid in the Rural Areas. PMID- 29007653 TI - The Hookworm and the War Loan. PMID- 29007655 TI - Notes on Current Topics. PMID- 29007654 TI - Notes on My Tour of Instruction. PMID- 29007656 TI - The Maternity Hospital, Madras. PMID- 29007657 TI - Use of Quinoidine. PMID- 29007658 TI - Gunshot Wounds in the Bengal Stationary Hospital, Amara, 1915-1916. PMID- 29007659 TI - Case Report-Ankylostomiasis. PMID- 29007660 TI - Medical Research in India. PMID- 29007661 TI - Some Cases. PMID- 29007662 TI - The Legal Aspect of Rupture of the Spleen. PMID- 29007664 TI - A New "Specific" for Malaria, Etc. PMID- 29007663 TI - Frontier Sores and Their Treatment by Antimony Injections. PMID- 29007666 TI - Service and War Notes. PMID- 29007665 TI - The New Calcutta Eye Hospital. PMID- 29007667 TI - A Case of Intestinal Obstruction Due to Ascaris Lumbricoides Perforation-Death. PMID- 29007668 TI - Further Experience in the Tartar Emetic Treatment of Kala-Azar Including Its Use in Young Children. PMID- 29007669 TI - Notes on Current Topics. PMID- 29007671 TI - General Hospital, Madras. PMID- 29007670 TI - The Use of Salvarsan. PMID- 29007673 TI - The Prize Essay on Syphilis Treatment. PMID- 29007672 TI - Carbolic Acid and Scorpion Stings. PMID- 29007674 TI - The Report of the Sanitary Commissioner, India, 1915. PMID- 29007675 TI - The King Institute, Guindy. PMID- 29007676 TI - The Birthday Honours List. PMID- 29007677 TI - The King Edward VII Memorial Pasteur Institute, Shillong. PMID- 29007678 TI - Iodine as an Antiseptic. PMID- 29007679 TI - The Treatment of Cutaneous Leishmaniasis with Intravenous Injections of Tartar Emetic. PMID- 29007681 TI - The Prevention of Sepsis in Cataract Extraction. PMID- 29007680 TI - Asthma and Ajwan Ash: A Cheap and Prompt Remedy. PMID- 29007683 TI - Gunshot Wounds of the Abdomen (During the Siege of Kut). PMID- 29007682 TI - Surface Tension and the Wassermann Reaction. PMID- 29007684 TI - The Influence of Beri-Beri on the Body Weight. PMID- 29007685 TI - Notes on Current Topics. PMID- 29007686 TI - Service and War Notes. PMID- 29007687 TI - Cataract Operation "Old" and "New": Site of Election for Incision in Cataract Extraction. PMID- 29007688 TI - Vitreous Escape. PMID- 29007689 TI - Gorget Patches. PMID- 29007691 TI - The Public Services Commission: Extracts from the Report. PMID- 29007690 TI - A Case of Hysterical Coma Successfully Treated by Stimulants. PMID- 29007692 TI - The Pharmaceutical Section for India: Established in December, 1916. PMID- 29007693 TI - Quinine Idiosyncracy in Five Cases. PMID- 29007694 TI - Intravenous Eusol in Plague. PMID- 29007695 TI - Prison Diets in India and Egypt. PMID- 29007696 TI - Ulcerating Granuloma of the Pudenda. PMID- 29007697 TI - A Case of Tetanus. PMID- 29007698 TI - A Plea for Painless Child-Birth in India. PMID- 29007699 TI - A Case of Camphor Poisoning. PMID- 29007700 TI - Early Diagnosis of Leprosy. PMID- 29007701 TI - Notes on Current Topics. PMID- 29007702 TI - Service and War Notes. PMID- 29007703 TI - Some Further Hints on the Treatment of Kala-Azar with Antimony Tartrate. PMID- 29007704 TI - Dr. Willis' Alleged Specific. PMID- 29007705 TI - Fourth Report on the Treatment of Kala-Azar and Some Blood Reactions in This Disease. PMID- 29007706 TI - The Public Services Commission's Report. PMID- 29007707 TI - The Treatment of Diabetes by Alimentary Rest. PMID- 29007708 TI - The Comparative Mortality of the Towns in the Nadia District. PMID- 29007709 TI - Medical Meeting at Kut. PMID- 29007710 TI - Gangosa. PMID- 29007711 TI - Medical Aid in the Rural Areas. PMID- 29007712 TI - Ulcerating Granuloma of the Pudenda. PMID- 29007713 TI - Scurvy.-A Short Note. PMID- 29007715 TI - Service and War Notes. PMID- 29007714 TI - The Surgical Aspect of the Ruptured Spleen with Note on Cases. PMID- 29007717 TI - Diabetes and Alimentary Rest. PMID- 29007716 TI - Scarlet R. in Certain Diseases of the Conjunctiva and Cornea. PMID- 29007718 TI - A Case of Lumbar Puncture for the Relief of Teething. PMID- 29007719 TI - Notes on Current Topics. PMID- 29007720 TI - Medical Conference in Bombay. PMID- 29007721 TI - A New War Splint for Fractured Femur. PMID- 29007722 TI - Notes on My Tour of Instruction. PMID- 29007723 TI - The Quarantine Station of Tor. PMID- 29007725 TI - Chronic Diarrhoea Radically Cured by Emetine Hydrochlor. PMID- 29007724 TI - Service and War Notes. PMID- 29007726 TI - War Honours in the I.M.S. PMID- 29007727 TI - A Double Monster. PMID- 29007728 TI - A Rise of Temperature in Algide Malaria. PMID- 29007730 TI - Notes on Current Topics. PMID- 29007729 TI - Intravenous Tartar Emetic in Crescentic Malaria. PMID- 29007731 TI - Medical Society. PMID- 29007732 TI - Accidental Suffocation, Important from a Medico-Legal Point of View. PMID- 29007733 TI - Science and the Nation. PMID- 29007734 TI - Relapsing Fever in Seistan. PMID- 29007735 TI - Disposal of Human Excreta in Standing Camps. PMID- 29007737 TI - The Life History of Ascaris Lumbricoides. PMID- 29007736 TI - Infantile Biliary Cirrhosis. PMID- 29007738 TI - Case of Ulcerating Granuloma (?). PMID- 29007739 TI - How to Administer Quinine. PMID- 29007740 TI - Cholera. PMID- 29007741 TI - Sprue Treated by Emetine. PMID- 29007742 TI - The Life History of Ascaris Lumbricoides. PMID- 29007743 TI - The Case of the Disabled Soldiers. PMID- 29007744 TI - War Emergency Fund of the Royal Medical Benevolent Fund. PMID- 29007745 TI - Eusol in Plague. PMID- 29007746 TI - Tablet v. Tabloid. PMID- 29007748 TI - Medical Society. PMID- 29007747 TI - Treatment of Ulcerative Granuloma. PMID- 29007749 TI - Colitis in Waziristan and Its Prevention. PMID- 29007750 TI - Notes on Current Topics. PMID- 29007751 TI - The Sterilization of Water by Chlorine and Hypo-Chlorites. PMID- 29007752 TI - Service and War Notes. PMID- 29007753 TI - Forgotten Pages of Jail History. PMID- 29007754 TI - The Bombay Medical Registration Act. PMID- 29007755 TI - Tetanus and Hypodermic Quinine. PMID- 29007756 TI - The Evacuation of Serious Cases in Mountain Warfare. PMID- 29007757 TI - The Prophylaxis of Malaria. PMID- 29007758 TI - The Cuckoo Psychology of Sir Oliver Lodge. PMID- 29007759 TI - Ophthalmic Work in Madras. PMID- 29007760 TI - Some Cases. PMID- 29007762 TI - Service and War Notes. PMID- 29007761 TI - Further Experience in the Tartar Emetic Treatment of Kala-Azar Including Its Use in Young Children. PMID- 29007763 TI - A Case of Dextrocardia. PMID- 29007764 TI - The Advent of Colloidal Alkaloids. PMID- 29007765 TI - Jail Dysentery. PMID- 29007766 TI - National Committee for Relief in Belgium. PMID- 29007768 TI - Notes on Current Topics. PMID- 29007767 TI - Divergent Views on Suppuration after Cataract Operation. PMID- 29007769 TI - Major Stewart on Ascaris Infection. PMID- 29007771 TI - A Case of Lithopoedian. PMID- 29007770 TI - Note on Ascaris Infection in Man, the Pig, Rat, and Mouse. PMID- 29007772 TI - Hydatid Disease in Kathiawar. PMID- 29007773 TI - Irrigation after Extra-Capsular Extraction of Cataract. 500 Cases. PMID- 29007774 TI - Ascaris Lumbricoides and Coprophagia. PMID- 29007775 TI - A Medico-Legal Case. PMID- 29007776 TI - Medical Society. PMID- 29007777 TI - The "New Operation for Cataract". PMID- 29007779 TI - Case of Difficult Labour. PMID- 29007778 TI - Legro's Solution and Snake Bites. PMID- 29007780 TI - A Probable Factor in Diabetes. PMID- 29007782 TI - Hypertrophy of the Male Breast. PMID- 29007781 TI - Successful Treatment of Solid OEdema of Scrotum and Penis by Silk Strands. PMID- 29007783 TI - The Prevention of Sepsis in Cataract Extraction. PMID- 29007784 TI - The New Journal of British Opthalmology. PMID- 29007785 TI - Some Notes from the Study of the After-Treatment of War Injuries and Disabilities. PMID- 29007786 TI - Notes on Current Topics. PMID- 29007787 TI - Cholera and Its Prevention. PMID- 29007788 TI - Purification of Water by Free Chlorine. PMID- 29007789 TI - Surgical Notes at a War Hospital. PMID- 29007791 TI - Indian Jail Health Statistics: 1915. PMID- 29007790 TI - A Case of Fever Resembling Brill's Disease. PMID- 29007792 TI - Treatment of Scorpion Stings. PMID- 29007793 TI - Water Purification. PMID- 29007795 TI - Service and War Notes. PMID- 29007794 TI - Corrigendum. AB - [This corrects the article on p. 408 in vol. 51.]. PMID- 29007796 TI - Chronic Splenomegaly in Lower Bengal with Special Reference to the Prevalence and Clinical Differentiation of Kala-Azar. PMID- 29007798 TI - An Epidemiological Note on Kala-Azar. PMID- 29007797 TI - Sub-Assistant Surgeons. PMID- 29007799 TI - Sir William Edwards. PMID- 29007800 TI - Notes on Current Topics. PMID- 29007801 TI - Treatment of Chronic Gonorrhoea: A Few Cases. PMID- 29007802 TI - A Note on the First Six Months' Work of the Radium Institute, at Ranchi. PMID- 29007803 TI - Intravenous Air Embolism. PMID- 29007805 TI - Erratum: Echinococcal Infection of the Eyeball. AB - [This corrects the article on p. 376 in vol. 57.]. PMID- 29007804 TI - A Scheme of Medical Inspection of Scholars in Secondary Schools. PMID- 29007806 TI - Two Family Outbreaks of the Epidemic Dropsy Type of Beri-Beri. PMID- 29007807 TI - The Merits of the Ayurvedic System of Medicine. PMID- 29007809 TI - The Rate of Growth of Vesical Calculi. PMID- 29007808 TI - The Season of Onset of Kala-Azar. PMID- 29007810 TI - Service Notes. PMID- 29007811 TI - A Live Museum. PMID- 29007812 TI - Expression versus Capsulotomy. PMID- 29007813 TI - Expulsive Haemorrhage. After Cataract Extraction. PMID- 29007814 TI - A Snake-Bite Poster. PMID- 29007815 TI - Further Notes on Filariasis. PMID- 29007817 TI - The Operative Treatment of Trachoma by Excision of the Fornix. PMID- 29007816 TI - Rarer Types of Fractures. PMID- 29007819 TI - Service Notes. PMID- 29007818 TI - A Preliminary Note on the Relationship of the Intestinal Protozoa of Man to the Hydrogen Ion Concentration of Their Environment. PMID- 29007820 TI - Filariasis Research Enquiry. PMID- 29007821 TI - Our Hospitals and Dispensaries. PMID- 29007822 TI - A Day in the Life of a Port Health Officer. PMID- 29007823 TI - A Case of Broncho-Moniliasis. PMID- 29007824 TI - The Beri-Beri and Epidemic Dropsy Problem: Part I. PMID- 29007825 TI - An Accessory Mouth. PMID- 29007826 TI - The Treatment of Rhinosporidium by Antimony Tartrate. PMID- 29007828 TI - "Economy" and Medical Research. PMID- 29007827 TI - A Case of Idiopathic Dilatation of the Colon. PMID- 29007829 TI - Erratum: Rarer Types of Fractures: A Correction. AB - [This corrects the article on p. 68 in vol. 58.]. PMID- 29007830 TI - Notes on Current Topics. PMID- 29007831 TI - Strongyloidosis. PMID- 29007832 TI - A Case of Stone in the Bladder Removed by Midwifery Forceps. PMID- 29007833 TI - An Unusual Termination of Pyo-Pneumo-Thorax Secondary to Pneumonia. PMID- 29007834 TI - Relapsing Fever in Raichur. PMID- 29007836 TI - Filariasis and Haemoptysis. PMID- 29007835 TI - Edward Jenner, 1749-1823. PMID- 29007837 TI - An Aseptic Thermometer Case. PMID- 29007838 TI - "Bayer 205" in Kala-Azar. PMID- 29007839 TI - A Note upon Spleen Puncture Findings in Malaria. PMID- 29007840 TI - End Results in Intra-Capsular Extraction (Smith's). PMID- 29007841 TI - Punarnava. PMID- 29007842 TI - The Pharmacology and Therapeutics of Boerhaavia Diffusa (Punarnava). PMID- 29007843 TI - Cysticercus of the Subconjunctival Tissues. PMID- 29007844 TI - The Biology of Death. PMID- 29007845 TI - Antimony-Fast Kala-Azar. PMID- 29007846 TI - Expression versus Capsulotomy. PMID- 29007847 TI - A Case of Intestinal Obstruction Complicated by Tetanus. PMID- 29007848 TI - A Fatal Case of Cerebral Contusion. PMID- 29007849 TI - Notes on Current Topics. PMID- 29007850 TI - OEdema Following Plague. PMID- 29007851 TI - The Beri-Beri and Epidemic Dropsy Problem: Part II. PMID- 29007853 TI - Service Notes. PMID- 29007852 TI - A Case of Food Sensitiveness. PMID- 29007854 TI - An Unusual Infection with Bacillus Pyocyaneus Simulating Leprosy. PMID- 29007856 TI - Ophthalmology in Egypt and Its Possibilities in India. PMID- 29007855 TI - A Short Note Concerning a New Method of Treatment for Inoperable Cancer. PMID- 29007857 TI - Bacteriological Notes on an Epidemic of Seven-Day Fever. PMID- 29007858 TI - The Surgical Treatment of Chronic Dyspepsia. PMID- 29007859 TI - Notes on Current Topics. PMID- 29007861 TI - Medical Research, Its Aims and Economic Value. PMID- 29007863 TI - A Case of OEdema of the Leg Following Plague. PMID- 29007862 TI - Insulin and Diabetes in India. PMID- 29007860 TI - Further Practical Experience with the Aldehyde Test. PMID- 29007864 TI - Therapeutics of the Cinchona Alkaloids. PMID- 29007866 TI - Berger's Stereoscopic Lenses for Ophthalmic Practice. PMID- 29007865 TI - An Aseptic Thermometer Case. PMID- 29007867 TI - A Case of Quintuplets. PMID- 29007868 TI - Relapsing Fever in Panama. PMID- 29007869 TI - Service Notes. PMID- 29007871 TI - A Case of Encephalitis Lethargica with Parkinsonian Syndrome. PMID- 29007870 TI - The Field for Research in Indian Indigenous Drugs. PMID- 29007872 TI - Notice to Contributors. PMID- 29007873 TI - Kala-Azar in the Madras Presidency outside Madras City. PMID- 29007875 TI - Thirty Years' Experience of Kala-Azar in the Nowgong District of Assam. PMID- 29007874 TI - The Kala-Azar Transmission Problem. PMID- 29007877 TI - Kala-Azar in India. The Present Position. PMID- 29007876 TI - Stab Wound of Enlarged Spleen. PMID- 29007878 TI - An Unusually Large Supraclavicular Lipoma. PMID- 29007879 TI - Notes on the Results of Treatment of Cases of Kala-Azar Admitted to the Madras City Hospitals between 1913-22. PMID- 29007880 TI - A Case of Acute Intestinal Obstruction. PMID- 29007881 TI - Iodine in the Treatment of Malaria, Kala-Azar and Small-Pox. PMID- 29007882 TI - Clinical Kala-Azar Work Performed at the Special Kala-Azar Hospital, Shillong, during 1922. PMID- 29007883 TI - The Evidence of Cure in the Treatment of Kala-Azar by Antimony. PMID- 29007884 TI - An Epidemiological Study of 663 Cases of Kala-Azar Admitted to the Madras City Hospitals between 1913-1922. PMID- 29007885 TI - A New Instrument for the Taking Uncontaminated Swabs from the Interior of the Uterus. PMID- 29007886 TI - Notes on Current Topics. PMID- 29007887 TI - The Globulin Opacity Test for Kala-Azar. PMID- 29007888 TI - The Incidence of Kala-Azar in Bengal. PMID- 29007889 TI - An Unusual Complication in Kala-Azar. PMID- 29007890 TI - The Differential Leucocyte Count. PMID- 29007891 TI - A Case for Diagnosis. PMID- 29007892 TI - Service Notes. PMID- 29007893 TI - A Case of Auricular Fibrillation Restored to Normal Rhythm. PMID- 29007894 TI - Some Notes on the Transmission of Leprosy. PMID- 29007896 TI - Notes on Current Topics. PMID- 29007895 TI - Our Present Knowledge of Insulin. PMID- 29007898 TI - Two Fatal Cases of Snake Bite. PMID- 29007897 TI - A Case of Ocular Paralysis with Glycosuria. PMID- 29007899 TI - An Automatic Fly-Proof Latrine Seat. PMID- 29007901 TI - A Case of Hernia Obstructed by Mesenteric Glands. PMID- 29007900 TI - Two Unusual Sarcomatous Tumours. PMID- 29007902 TI - The Dietetic Value of Sago. PMID- 29007904 TI - The Far Eastern Association of Tropical Medicine Congress. PMID- 29007903 TI - Intravenous Sodium Salicylate. PMID- 29007905 TI - A Case of Fasciolopsis Buski Infection. PMID- 29007906 TI - Ankylostomiasis Problem. PMID- 29007907 TI - The Treatment of Kala-Azar by Meta-Chlor-Para-Acetyl-Amino-Phenyl Stibiate of Sodium. PMID- 29007908 TI - A Case of Infantile Biliary Cirrhosis. PMID- 29007909 TI - A Sensitised Anti-Plague Vaccine. PMID- 29007910 TI - The Therapeutic Value of Intravenous Iodine: Based on Three Years' Experience on 400 Cases. PMID- 29007911 TI - Hookworm Dissemination. PMID- 29007912 TI - A Vacuum Apparatus for Cataract Extraction. Record of Failure. PMID- 29007913 TI - Stone in the Nasal Cavity. PMID- 29007914 TI - A Note on the Complications Following 1,322 Consecutive Cases of Cataract Extraction. PMID- 29007915 TI - Plasmodium Tenue and P. Ovale. PMID- 29007916 TI - Plasmodium Tenue and P. Ovale. PMID- 29007917 TI - A Case of Ingestion of Hair by an Infant, with Symptoms Simulating Dysentery. PMID- 29007918 TI - A New Treatment for Naga Sore. PMID- 29007919 TI - Hookworm Infection in the Coal Mines of Bengal. PMID- 29007920 TI - An Abnormal Hernia. PMID- 29007921 TI - A Preliminary Note on the Radium Treatment of New Growths without the Direct Application of Radium. PMID- 29007922 TI - Notes on Some Cases of Framboesia. PMID- 29007923 TI - Clinical Notes on Four Consecutive Laryngeal Cases. PMID- 29007925 TI - Notes on Current Topics. PMID- 29007924 TI - A Case of Aneurysm Rupturing into the Pericardium. PMID- 29007926 TI - Carbon Tetrachloride in Pharmacology and Therapeutics. PMID- 29007927 TI - Service Notes. PMID- 29007928 TI - The Memoirs of Sir Ronald Ross. PMID- 29007929 TI - An Unusual Complication in an Acute Case of Kala-Azar. PMID- 29007930 TI - An Unusual Sequel of Trachoma. PMID- 29007931 TI - Some Notes on a Malaria Investigation on a Sugar Estate in Kamrup, Assam. PMID- 29007932 TI - A Note to Contributors. PMID- 29007933 TI - The Use of Germinated Pulse and Beans in the Natural Dietary of the Burmese. PMID- 29007934 TI - A Case of Absence of the Left Lung. PMID- 29007935 TI - Note on an Investigation into the Value of Essential Oils in the Prevention and Treatment of Cholera. PMID- 29007936 TI - Five Consecutive Cases of Tetanus Ending in Recovery. PMID- 29007937 TI - Spinal Analgesia. PMID- 29007938 TI - The Ankylostomiasis Problem. PMID- 29007939 TI - Expression versus Capsulotomy. PMID- 29007940 TI - A Case of Abdomen Punctured by a Broken Bottle. PMID- 29007941 TI - The Influence of the Substrate on the Action of Drugs. PMID- 29007942 TI - Berger's Stereoscopic Lenses. PMID- 29007944 TI - Service Notes. PMID- 29007943 TI - Obstetric Impressions. PMID- 29007945 TI - Glucose Tolerance Tests and Their Interpretation. PMID- 29007946 TI - A Short Note on the Improvement of the Poona Water Supply by Simple Storage. PMID- 29007947 TI - Gonorrhoea of the Female Genital Organs and Its Management. PMID- 29007948 TI - A Plea for the Inception of a Mental Hygiene Movement in India. PMID- 29007950 TI - Notes on Current Topics. PMID- 29007949 TI - A Case of Hydatid Cyst of the Liver. PMID- 29007952 TI - The Training of Public Health Officials. PMID- 29007951 TI - The Medical Profession in India. PMID- 29007953 TI - A Case of Raynaud's Disease. PMID- 29007954 TI - A Further Note on Myiasis of the Frontal Sinus. PMID- 29007955 TI - Cholelithiasis and Its Significance. PMID- 29007956 TI - Vitreous Escape in Intracapsular Extraction of Cataract in Prominent Eye-Balls or Fat Patients. PMID- 29007957 TI - The Bengal Forceps: A Modified Obstetric Forceps for Use in Bengali Women. PMID- 29007958 TI - Two Cases of Death from Haemorrhage into the Pericardium. PMID- 29007959 TI - Spinal Analgesia. PMID- 29007960 TI - Ourselves. PMID- 29007961 TI - The Indian Medical Year, 1922. PMID- 29007962 TI - A Case of Unusual Mal-Presentation. PMID- 29007963 TI - The Therapeutics of Antimony. PMID- 29007964 TI - Cataract versus Expression. PMID- 29007966 TI - The Use of a Non-Motile Strain of B. Typhosus in the Agglutination Reaction. PMID- 29007965 TI - What Are the Departures from Health and the Diseases Which Arise from the Negligence, Ignorance and Self-Indulgence of Man. PMID- 29007967 TI - A Case of Homicidal Yellow Oleander Poisoning. PMID- 29007968 TI - Notes on Current Topics. PMID- 29007969 TI - Personal Observations on a Few Cases of Kala-Azar. PMID- 29007970 TI - The Economy Axe. PMID- 29007971 TI - Service Notes. PMID- 29007972 TI - Antimony-Fast Kala-Azar. PMID- 29007974 TI - The Tuberculosis Problem in India. PMID- 29007973 TI - A Malaria Survey of Sawantwadi State. PMID- 29007975 TI - Electrolytic Chlorogen. PMID- 29007976 TI - The Dengue-Sand-Fly Fever Problem. PMID- 29007977 TI - Great Engineering Works and Their Medical Aspects. PMID- 29007978 TI - Some Observations on the Dietary of Scholars. PMID- 29007979 TI - Electrolytic Chlorogen. PMID- 29007980 TI - Colonel King on Sanitation in India. PMID- 29007981 TI - A Note on the Effect of Intravenous Injections of Antimony Tartrate upon the Development of Vaccinia Virus. PMID- 29007982 TI - Filarial Haemoptysis. PMID- 29007983 TI - The Occurrence of Balantidium Coli in the Faeces of an Indian. PMID- 29007985 TI - The Treatment of Malaria by Quinine in Combination with Magnesium Sulphate and Alkali. PMID- 29007984 TI - The British Medical Association. PMID- 29007986 TI - Cancrum Oris Treated by Excision and Subsequent Tube Grafting. PMID- 29007988 TI - Observations on an Outbreak of Diphtheria at Bishop Cotton's School, Simla. PMID- 29007989 TI - Service Notes. PMID- 29007987 TI - Three Similar Yet Dissimilar Cases of Gynaecological Interest. PMID- 29007991 TI - Tetanus in Intestinal Cases. PMID- 29007990 TI - The Schick Test and Immunisation by Toxin-Anti-Toxin in Assam. PMID- 29007992 TI - Four Interesting Cases. PMID- 29007993 TI - The Dissemination of Human Helminthic Infections by Animals. PMID- 29007994 TI - The Failure of "Bayer 205" in the Treatment of Kala-Azar. PMID- 29007995 TI - Notes on Current Topics. PMID- 29007997 TI - A Case of Molluscum Fibrosum. PMID- 29007996 TI - Artificial Pneumothorax and Other Surgical Methods in Advanced Tuberculosis and Pleurisy. PMID- 29007998 TI - Avoidable Cancer. PMID- 29007999 TI - A Case of Progressive Muscular Dystrophy. PMID- 29008000 TI - Notes on Current Topics. PMID- 29008001 TI - British Income Tax Refunds. PMID- 29008002 TI - Treatment of Oxyuris Infection. PMID- 29008003 TI - Kala-Azar in Bengal. PMID- 29008005 TI - A Punctured Wound of the Abdomen. PMID- 29008004 TI - Gleanings from the Records of the Government Maternity Hospital, Madras. PMID- 29008006 TI - Cultural Examination of the Urine in Kala-Azar. PMID- 29008008 TI - Service Notes. PMID- 29008007 TI - Intravenous Iodine in the Treatment of Septic Wounds. PMID- 29008009 TI - The Pandemic of Influenza in India in the Year 1918. PMID- 29008010 TI - A Case for Diagnosis. PMID- 29008011 TI - A Case of Diabetic Coma Treated with Insulin. PMID- 29008012 TI - The Psychopathic Child. PMID- 29008014 TI - Service Notes. PMID- 29008013 TI - Medical Research and Public Health, the Present Position in India. PMID- 29008015 TI - Removal of Tattoo Marks. PMID- 29008016 TI - The "Aldehyde Test" in Malaria. PMID- 29008017 TI - Medical Research and Sanitary Engineering. PMID- 29008018 TI - A Case of Blindness Preceding Apoplexy. PMID- 29008019 TI - A Case of Lipoma of the Thigh. PMID- 29008020 TI - The Causation of Asthma and Its Treatment. PMID- 29008021 TI - Experiments with Thyroid Augmentor and a Note on the Post-Operative Treatment of Exophthalmic Goitre. PMID- 29008022 TI - The Possibility of Latent Infection with B. Typhosus. PMID- 29008023 TI - Some Observations on Dysentery. PMID- 29008024 TI - Insulin. PMID- 29008025 TI - A Multilocular Ovarian Cyst. PMID- 29008026 TI - A Case of Splenectomy. PMID- 29008027 TI - A Case of Hydatid Cysts of Both Lobes of the Liver. PMID- 29008028 TI - The Treatment of Rheumatism by Sodium Salicylate Injections. PMID- 29008029 TI - The Operative Treatment of Fractures. PMID- 29008030 TI - Some Eye Cases. PMID- 29008031 TI - A Series of Cases Resembling Paralytic Ileus. PMID- 29008032 TI - Streptococcal Affections of the Skin. PMID- 29008033 TI - Notes on Current Topics. PMID- 29008035 TI - Notes on Current Topics. PMID- 29008034 TI - Eye Strain. PMID- 29008036 TI - "Epigastric Hernia" in Sepoys. PMID- 29008037 TI - A Note on Cholera Inoculation Carried out on the North-West Frontier, 1915. PMID- 29008038 TI - Reflections on Cataract Extraction. PMID- 29008040 TI - The Calcutta Tropical School. PMID- 29008039 TI - Service and War Notes. PMID- 29008042 TI - Sugar Tolerance in Medical Practice. PMID- 29008041 TI - A Proposal for a District Sanitary League. PMID- 29008044 TI - Bacteriology of Dysentery in Malaya. PMID- 29008043 TI - Corrigendum. AB - [This corrects the article on p. 207 in vol. 51.]. PMID- 29008045 TI - Royal Medical Benevolent Fund. PMID- 29008046 TI - Double Inguinal Hernia. PMID- 29008047 TI - The Value of Quinoidine in Malaria. PMID- 29008048 TI - The "New" Operation for Cataract. PMID- 29008050 TI - Likewise and Contrarywise. PMID- 29008051 TI - Cataract Operations "Old" and "New". PMID- 29008049 TI - Hymenolepis Nana. PMID- 29008052 TI - A Reply to Lieut.-Col. Sutherland, I.M.S. PMID- 29008053 TI - Salvarsan Injections. PMID- 29008054 TI - The Treatment of Trachoma by Excision of the Tarsus and Tarsal Conjunctiva of the Upper Lid. PMID- 29008055 TI - Public Health Statistics, India. PMID- 29008056 TI - Diarrhoea and Continuous Fever Due to Oysters. PMID- 29008057 TI - Notes on Current Topics. PMID- 29008058 TI - Some Queries. PMID- 29008059 TI - The Madras General Hospital Report. PMID- 29008060 TI - Service and War Notes. PMID- 29008062 TI - Civil Leave Rules. PMID- 29008061 TI - Third Eruption of Teeth in Old Age. PMID- 29008063 TI - Sandfly Fever and Dengue. PMID- 29008064 TI - Corrigendum. AB - [This corrects the article on p. 308 in vol. 51.]. PMID- 29008065 TI - Glaucoma Operations. PMID- 29008066 TI - Case of Pellagra in Alipur Jail. PMID- 29008067 TI - The Use of Eusol. PMID- 29008068 TI - General Paralysis of the Insane. PMID- 29008069 TI - Surgery at the Siege of Kut: December 5th, 1915, to April 29th, 1916. PMID- 29008071 TI - Service and War Notes. PMID- 29008070 TI - Ovarian Cyst, Complicating Pregnancy. PMID- 29008073 TI - Medical Colleges and Schools in India. PMID- 29008072 TI - Abdominal and Bovine Tuberculosis in India. PMID- 29008074 TI - A Cheap Absorbent Dressing for the Wounded. Incinerated Paddy Husk. PMID- 29008076 TI - The Solubility of Quinoidine. PMID- 29008075 TI - Cases of Hurt. PMID- 29008077 TI - Notes on Current Topics. PMID- 29008078 TI - The Purification of the Water-Supply of the Lawrence Military Asylum, Sanawar, by Means of Bleaching Powder. PMID- 29008079 TI - Iron and Arsenic as a Cure for and a Prophylactic against Malaria. PMID- 29008081 TI - The Canal Zone Med. Association. PMID- 29008080 TI - Colouring the Eye-Ball. PMID- 29008083 TI - The King Institute, Guindy. PMID- 29008082 TI - A Case of Pellagra. PMID- 29008084 TI - A Case of Siamese Twins in Mayavaram. PMID- 29008086 TI - A Case of Snake-Bite (Lachesis Borneensis). PMID- 29008085 TI - The Use of Residual Alkaloids of Cinchona. PMID- 29008087 TI - The "New" Method of Extracting Cataractous Lenses. PMID- 29008089 TI - Soda Salicylas in Appendicitis and Peritonitis. PMID- 29008088 TI - Malaria in Bengal. PMID- 29008090 TI - Notes on Current Topics. PMID- 29008091 TI - Persistent Hymen. PMID- 29008092 TI - Round Worms. PMID- 29008093 TI - A Readily Made Splint for Compound Fractures of the Femur and the Bones of the Leg. PMID- 29008094 TI - Service and War Notes. PMID- 29008095 TI - The Prophylaxis of Malaria. PMID- 29008096 TI - Corrigendum. AB - [This corrects the article on p. 196 in vol. 51.]. PMID- 29008097 TI - Ischiopagus Duplicity and Certain Teratoid Growths of the Pelvic Region. PMID- 29008098 TI - Hymenolepis Nana (Siebold) (The Dwarf Tapeworm) as a Parasite of Indian Soldiers. PMID- 29008099 TI - Remarks on Dr. Hossack's Paper on "German Influence on Modern Bacteriology": The Need for Elimination and Revision. PMID- 29008100 TI - Cataract Operations "Old" and "New" II. PMID- 29008101 TI - Weight of Lungs. PMID- 29008102 TI - Abdominal Abscess Caused by Ascaris Lumbricoides. PMID- 29008104 TI - The Trip to Busrah. PMID- 29008103 TI - Intestinal Parasites in the Central Jail, Rajahmundry. PMID- 29008105 TI - Beta-Naphthol in Ankylostomiasis. PMID- 29008106 TI - A Case of Impetigo Bullosa. PMID- 29008107 TI - Vesico-Vaginal Fistulae. PMID- 29008109 TI - A Medico-Legal Suggestion. PMID- 29008108 TI - The Uses of Pituitary Extract in Labour, at the Government Maternity Hospital, Madras. PMID- 29008110 TI - Grievous Hurt. PMID- 29008112 TI - Service and War Notes. PMID- 29008111 TI - Medical and Surgical Notes at Miraj Hospital. PMID- 29008114 TI - Notes on Current Topics. PMID- 29008113 TI - Tuberculosis in the Indian Army in France. PMID- 29008116 TI - Indigenous Drugs Research. PMID- 29008115 TI - Ectopic Gestation :-Rupture: Operation: Recovery. PMID- 29008117 TI - Noguchi's Serum Test for Syphilis. PMID- 29008119 TI - Gynocardates in Leprosy. PMID- 29008118 TI - A Lucky Wound. PMID- 29008120 TI - Septic Wounds Affecting English and Indian Troops: A Comparison. PMID- 29008122 TI - Tropical Expedition to Honduras. PMID- 29008121 TI - Vesico-Vaginal Fistulae. PMID- 29008123 TI - The War and the Sub-Assistant-Surgeons in Bengal. PMID- 29008124 TI - Injuries to Peripheral Nerves. PMID- 29008125 TI - Corrigendum. AB - [This corrects the article on p. 121 in vol. 51.]. PMID- 29008127 TI - The Causes of Failure after Visual Iridectomy. PMID- 29008126 TI - Tetanus. PMID- 29008128 TI - Treatment of Kala-Azar with Special Reference to the Use of Antimony and Formaldehyde. PMID- 29008129 TI - Service and War Notes. PMID- 29008130 TI - Police Cases. PMID- 29008131 TI - Intravenous Saline in Cholera-A Contra Indication. PMID- 29008132 TI - Gunshot Wound of the Foot. PMID- 29008133 TI - Medical Education Problems in India. PMID- 29008135 TI - Notes on Current Topics. PMID- 29008134 TI - German Influence on Modern Bacteriology-The Need for Elimination and Revision. PMID- 29008136 TI - The Correct Names of the Helminths of Man. PMID- 29008137 TI - Some Experiences in a Depot Hospital. PMID- 29008138 TI - The Evolution of Intracapsular Extraction of Cataract. PMID- 29008139 TI - Interesting Cases from the Medical Wards of the Medical College Hospital, Calcutta. PMID- 29008140 TI - Supernumerary Fingers and Toes. PMID- 29008141 TI - Notes on Current Topics. PMID- 29008143 TI - Cataract Operation "Old" and "New". PMID- 29008142 TI - Two Photographs of Bullets Extracted from Sepoys in France and Mesopotamia. PMID- 29008144 TI - Dreaming. PMID- 29008146 TI - Septic Shell Wounds. PMID- 29008145 TI - Quinoidine and Malaria. PMID- 29008147 TI - Hypertrophy of the Male Breast. PMID- 29008149 TI - Onset and March of Glycosuria. PMID- 29008148 TI - Gynocardate of Soda Intravenously in Leprosy. PMID- 29008150 TI - The Wassermann Reaction. PMID- 29008152 TI - Treatment of Scorpion Stings. PMID- 29008151 TI - Some Recent Advances in Cardiology. PMID- 29008153 TI - Service and War Notes. PMID- 29008154 TI - "Eupad" in Sterilization of the Surgeon's Hand. PMID- 29008155 TI - Comments on Case of Blackwater Fever. PMID- 29008156 TI - Tetanus and Amputation. PMID- 29008157 TI - Health and Mortality among Educated Indians. PMID- 29008158 TI - Service and War Notes. PMID- 29008159 TI - Eusol and Plague : A Suggestion. PMID- 29008160 TI - The Suprapubic Operation or Litholapaxy. PMID- 29008162 TI - Eosinophilia in Some Cases of Helminthiasis. PMID- 29008161 TI - The Training of the Assistant in Smith's Operation. PMID- 29008163 TI - The New Psychiatry. PMID- 29008164 TI - The "New Operation for Cataract". PMID- 29008165 TI - Notes on Emergent Abdominal Surgery. PMID- 29008166 TI - Quinine and Malaria. PMID- 29008167 TI - The New Method of Extraction of Cataractous Lenses. PMID- 29008168 TI - Notes on Current Topics. PMID- 29008169 TI - The Conjunctival Flap. PMID- 29008170 TI - A Note on the Use of a Conjunctival Flap in Operations for the Intra-Capsular Extraction of Cataract by Smith's Method. PMID- 29008171 TI - Vesical Calculus. PMID- 29008172 TI - Some Studies in Malaria in Nadia District: Monthly Variation of Malaria. PMID- 29008173 TI - Sarcoma of the Dura Mater. PMID- 29008174 TI - Hypochlorous Acid as an Antiseptic in Wounds. PMID- 29008175 TI - A New Method of Dressing Eyes after Cataract Extraction. PMID- 29008176 TI - Glycosuria and a Few Facts. PMID- 29008177 TI - Cataract Operations "Old" and "New". PMID- 29008178 TI - The Fed. Malay States' Report. PMID- 29008180 TI - Flies in a Jail. PMID- 29008179 TI - Some Gynaecological Laparotomies. PMID- 29008181 TI - Continuous Irrigation of Wounds in the Field. PMID- 29008182 TI - Treatment of Cholera. PMID- 29008183 TI - Notes on Current Topics. PMID- 29008184 TI - The I. M. S. and the F. R. S. PMID- 29008185 TI - Calcutta Tropical School. PMID- 29008186 TI - Service and War Notes. PMID- 29008187 TI - Peritomy and Keratitis. PMID- 29008188 TI - Annus Medicus, 1916. PMID- 29008189 TI - "Possessed by a Devil," with Its Treatment and Cure. PMID- 29008190 TI - Placenta Praevia. PMID- 29008191 TI - Tetanus and Hypodermic Quinine. PMID- 29008192 TI - Further Observations on the Treatment of Kala-Azar and Cases Treated with Metallic Antimonyl Sodium Tartrate, Formaldehyde and Other Drugs. PMID- 29008193 TI - Conjunctival Flaps in Cataract Operations. PMID- 29008194 TI - The Further Reduction of the Mortality of Cholera to 11 per Cent: By the Addition of Atropine Hypodermically to the Hypertonic and Permanganate Treatment, with an Addendum Summarising the System of Treatment. PMID- 29008196 TI - Notes on Current Topics. PMID- 29008195 TI - Two Madras Medical Lists. PMID- 29008197 TI - Large Stones in Bladder. PMID- 29008198 TI - Service and War Notes. PMID- 29008199 TI - Correspondence. PMID- 29008200 TI - A Case of Aneurysm of the Descending Thoracic Aorta. PMID- 29008202 TI - The Calcutta Tropical School. PMID- 29008201 TI - Hysteria (?) in the Young African. PMID- 29008203 TI - A Case of Anthrax Treated Successfully by Carbolic Acid. PMID- 29008204 TI - Correspondence. PMID- 29008206 TI - Service Notes. PMID- 29008205 TI - Improvised Triple-Bladed Bamboo Gastro-Enterostomy Clamps. PMID- 29008207 TI - On an Outbreak of Relapsing Fever in Turkey in 1918. PMID- 29008208 TI - Epithelioma of Upper Lip in a Boy 14 Years of Age. PMID- 29008209 TI - Professional Misconduct. PMID- 29008210 TI - Notes on a Case of Cystic Kidney. PMID- 29008211 TI - Standard Diets: A Lecture Delivered at the Calcutta Health and Child Welfare Exhibition. PMID- 29008212 TI - Typhus and Typhus-Like Fevers in Birjand, East Persia. PMID- 29008213 TI - Notes on Influenza. PMID- 29008214 TI - Current Topics. PMID- 29008215 TI - A Twenty-One Day Fever. PMID- 29008217 TI - The Pathogenesis of Diphtheritic Paralysis. PMID- 29008216 TI - Service Notes. PMID- 29008219 TI - Medical Inspection of Schools. PMID- 29008218 TI - Ulceration of the Stomach and Duodenum and the Resultant Obstruction in the Outlet of the Stomach Treated by Posterior Gastro-Enterostomy in a Series of 100 Cases. PMID- 29008220 TI - Current Topics. PMID- 29008221 TI - Case of Pneumococcal Arthritis Complicating Tonsillitis. PMID- 29008222 TI - Congenital Abnormalities. PMID- 29008224 TI - Typhus and Typhus-Like Fevers in Birjand, East Persia. PMID- 29008223 TI - Epinephrin in Typhoid. PMID- 29008225 TI - Further Observations on Kala-Azar. PMID- 29008226 TI - Second Series of 25 Cases of Malaria Treated by Hypodermic Injections of Cinchonine Bi-Hydrochloride. PMID- 29008227 TI - Cobra Poisoning. PMID- 29008228 TI - Acute Necrotic Parotitis. PMID- 29008230 TI - A Continuation from 1918 of the Report on Cases of Leprosy in Bangkok, Treated with Sodium Gynocardate "A". PMID- 29008229 TI - The Vitamine Value of the Date. PMID- 29008231 TI - The After-Treatment of Leprosy. PMID- 29008233 TI - Flying Worms. PMID- 29008232 TI - Notes on a Case of "Hypospadias Perinealis". PMID- 29008234 TI - Current Topics. PMID- 29008235 TI - A Case in Which the Bladder Was a Content of the Inguinal Canal. PMID- 29008236 TI - A Stone in the Scrotum. PMID- 29008237 TI - A Report on the Gynocardate and Morrhuate Treatment of Leprosy Based on Forty Cases Treated in the Kashmir State Leper Hospital. PMID- 29008238 TI - The Treatment of Leprosy. PMID- 29008239 TI - Influenza. PMID- 29008241 TI - Service Notes. PMID- 29008240 TI - Notes on Two Cases of Cerebrospinal Meningitis Due to the Diplococcus Intracellularis, Treated with Intrathecal Injections of Anti-Meningococcic Serum (Mulford), in a Field Ambulance in Mesopotamia. PMID- 29008242 TI - Sodium Morrhuate in Tuberculosis. PMID- 29008243 TI - The Result of Trials of Sodium Hydnocarpate and Sodium Morrhuate in Thirteen Indian Leper Asylums. PMID- 29008244 TI - Syphilis of the Circulatory System. PMID- 29008245 TI - Kala Azar in Europeans in the Nowgong District of Assam. PMID- 29008246 TI - Strictnre of the Male Urethera in India. PMID- 29008247 TI - The Work of a Vaccine Depot, Meiktila. PMID- 29008248 TI - A Preliminary Note on an Investigation as to the Actual Weight of the Cataractous Lens, Together with Some Clinical Notes on Cataract. PMID- 29008250 TI - Influenza as Observed in the Sambhu Nath Pundit Hospital, Calcutta. PMID- 29008249 TI - Sanitation "Oil Fuel Refuse Destructor," Basrah-Its Working and Economical Value. PMID- 29008252 TI - Diabetes in India. PMID- 29008253 TI - Service Notes. PMID- 29008251 TI - Current Topics. PMID- 29008254 TI - Brief Report on Cases of Probable Encephalitis Lethargica. PMID- 29008255 TI - Guinea Worm in the Inguinal Canal. PMID- 29008257 TI - Epidemic Encephalitis. PMID- 29008256 TI - An Interesting Case of Plague. PMID- 29008258 TI - Cervical Rib. PMID- 29008259 TI - Blackwater Fever. PMID- 29008260 TI - An Epidemic of Fifty-Four Cases of Relapsing Fever Observed in Birjand, East Persia. PMID- 29008261 TI - Impassable Strictures of the Urethra. PMID- 29008262 TI - Current Topics. PMID- 29008263 TI - Influenza. PMID- 29008265 TI - Report on Sixty-Four Cases of Eclampsia Treated at the Government Maternity Hospital, Madras, from October 1917, to October 1919. PMID- 29008264 TI - Cinchonidine in Malaria. PMID- 29008266 TI - Recent Researches on Rickets. PMID- 29008268 TI - Snake Venom as a Therapeutic Agent. PMID- 29008267 TI - Quinine Prophylaxis and the Treatment of Malaria in a Coolie Population: A Contribution from Assam. PMID- 29008269 TI - British Medical Association. PMID- 29008270 TI - Service Notes. PMID- 29008271 TI - Further Notes on the Treatment of Diabetes. PMID- 29008273 TI - Rupture of Gall-Bladder. PMID- 29008272 TI - Fifteen Cases of Ovarian Tumour Treated by Operation. PMID- 29008274 TI - A Preliminary Paper on Observations on Black Water Fever (Haemoglobinuria) in the Coorg Province, 1917-1918: Especially as Regards Its Etiological Factor, Namely, a Protozoan Parasite of the Genus Piroplasma in Conjunction with the Malarial Plasmodium; or a New and Undescribed Species of Laverania Malariae (Donovan's Theory). PMID- 29008276 TI - Death in the Pot. PMID- 29008275 TI - Note on the Open-Air Treatment of Pulmonary Tuberculosis in Madras Presidency. PMID- 29008277 TI - Epidemic Influenza in and around the City of Calcutta. PMID- 29008278 TI - Service Notes. PMID- 29008279 TI - Current Topics. PMID- 29008280 TI - Correspondence. PMID- 29008281 TI - Treatment of Kala-Azar with Intramuscular Injections of Hyper-Acid Antimonyl Tartrate (+Urethane). PMID- 29008283 TI - Correspondence. PMID- 29008284 TI - Correspondence. PMID- 29008282 TI - Abscess of Brain Due to Chronic Ear Disease. PMID- 29008286 TI - The General Medical Council and Midwifery. PMID- 29008285 TI - A Surgical Tour in the United States and Canada. PMID- 29008287 TI - The Presence of Infectious Jaundice in Bombay. PMID- 29008288 TI - The Prophylactic Value of Inoculation against Influenza from the Experience of an Epidemic at Khulna Jail. PMID- 29008289 TI - Extirpation of the Lachrymal Sac. PMID- 29008290 TI - The Annual Sanitary Report of the Province of Bihar and Orissa. PMID- 29008291 TI - Current Topics. PMID- 29008292 TI - Syphilis in Relation to Mental and Nervous Diseases. PMID- 29008293 TI - Report of a Case of Fungating Endocarditis (Streptococcal) Leading to Rupture of an Aortic Valve, Successfully Treated with Stock Serum and Autovaccine. PMID- 29008294 TI - Service Notes. PMID- 29008295 TI - Correspondence. PMID- 29008296 TI - Fracture of the Atlas and Axis Vertebrae. PMID- 29008297 TI - Prescribing for Symptoms. PMID- 29008298 TI - Measurement as the Basis of Diagnosis of the Furcocercous Cercariae. PMID- 29008299 TI - Correspondence. PMID- 29008300 TI - Current Topics. PMID- 29008301 TI - Correspondence. PMID- 29008302 TI - Ether in the Tropics. A New Apparatus. PMID- 29008304 TI - Notes from the Diary of a Medical Inspector of Schools. PMID- 29008305 TI - An Unusual Abdominal Tumour. PMID- 29008303 TI - The Role of Vitamins in Tropical Diseases. PMID- 29008307 TI - Service Notes. PMID- 29008306 TI - The Differential Blood Count. PMID- 29008308 TI - Yaws in Malaya. Its Treatment and Prophylaxis. PMID- 29008309 TI - A Difficult Obstetric Case after Ventro-Fixation of the Uterus. PMID- 29008310 TI - The Treatment of Malaria. PMID- 29008311 TI - A Case of Hypernephroma of Kidney. PMID- 29008312 TI - An Epidemic of So-Called Naga Sore at Unao. PMID- 29008313 TI - Indian Cantharides. PMID- 29008314 TI - A Case of Leucoderma. PMID- 29008315 TI - A Cyst over the Sternum. PMID- 29008316 TI - Rhinosporidium Kinealyi of the Conjunctiva. PMID- 29008317 TI - An Unusual Post-Operative Phenomenon in Thyroidectomy. PMID- 29008318 TI - A Case of Acute Inflammation of the Gall-Bladder in Which Gall Stones Were Found Fractured. PMID- 29008320 TI - The Calcutta School of Tropical Medicine and Hygiene. PMID- 29008319 TI - Removal of Tonsils and Adenoids. PMID- 29008321 TI - On the Operation of Prostatectomy. PMID- 29008323 TI - Alcohol as an AEtiological Factor in Cirrhosis of the Liver. PMID- 29008322 TI - Notes on Drugs: "Wellcome" Brand Lanoline and "Wellcome" Brand Lanoline Anhydrous. PMID- 29008324 TI - Science in Russia. PMID- 29008325 TI - Rhinosporidium Kinealyi of the Conjunctiva, Cured by Tartarated Antimony (Tartar Emetic), and Notes on a Case in Which the Lachrymal Sac Was Affected by This Sporozoon. PMID- 29008326 TI - Blackwater Fever as It Occurs in the Duars and Its Treatment. PMID- 29008328 TI - Current Topics. PMID- 29008327 TI - A Case of Pluriglandular Insufficiency. PMID- 29008329 TI - Laboratory Records from Mesopotamia. PMID- 29008330 TI - Note on a Case of a Typhus-Like Fever Occurring at Murree. PMID- 29008332 TI - Correspondence. PMID- 29008331 TI - A Case of Radical Cure of Irreducible Scrotal Hernia. PMID- 29008333 TI - A Case of Traumatic Myositis Ossificans. PMID- 29008334 TI - Current Topics. PMID- 29008335 TI - A Case of Fibroma Molluscum. PMID- 29008337 TI - Mass Treatment of Hookworm Infection. PMID- 29008336 TI - The Detection of Anthrax Spores in Shaving Brushes. PMID- 29008338 TI - The Annual Medical Report for Port Blair, 1921. PMID- 29008339 TI - Correspondence. PMID- 29008340 TI - The Pasteur Centenary. PMID- 29008342 TI - The Problems of Kala-Azar. PMID- 29008341 TI - Malignant Disease of the Retained or Imperfectly Descended Testis. PMID- 29008343 TI - Service Notes. PMID- 29008344 TI - India's Debt to Medical Research, Being the Presidential Address Delivered to the Medical Research Section, Indian Science - Congress. PMID- 29008345 TI - Indian Science Congress, 1922. PMID- 29008346 TI - Clinical Observations on Adhesion and Retention of the Membranes. PMID- 29008347 TI - Correction. AB - [This corrects the article on p. 401 in vol. 57.]. PMID- 29008348 TI - Ether in the Tropics: A Further Note. PMID- 29008349 TI - Report of Cases of Ankylostomiasis Treated in the District Hospital, Penang from 24-8-1921 to 31-12-1921. PMID- 29008350 TI - The Therapeutics of the Cinchona Alkaloids: Part II. PMID- 29008352 TI - A Case of Congenital Absence of the Spleen. PMID- 29008351 TI - Notes on a Case of Cataract in a Child, Following Lightning Stroke. PMID- 29008354 TI - The Abortive Treatment of Gonorrhoea. PMID- 29008353 TI - Service Notes. PMID- 29008355 TI - Notes on Relapsing Fever in Bhavnagar. PMID- 29008356 TI - A Case of Traumatic Aneurism of the Spleen. PMID- 29008357 TI - A Case of Tetanus. PMID- 29008359 TI - The Field for Research in Indian Indigenous Drugs. PMID- 29008358 TI - The Malarial Position in Assam. PMID- 29008360 TI - Notes on Some Cases Treated with Electrolytic Chlorogen (E. C.) at the Pusa Hospital. PMID- 29008361 TI - Current Topics. PMID- 29008362 TI - Capsulotomy versus Expression. PMID- 29008363 TI - Exceptional Hernias. PMID- 29008364 TI - A Case of Foreign Body (Fish) in the Air Passages, Removed by Laryngo Tracheotomy. PMID- 29008365 TI - An Analysis of the Clinical Picture in Kala-Azar: Part II. PMID- 29008366 TI - British Income Tax. PMID- 29008368 TI - A New Form of Cutaneous Leishmaniasis-Dermal Leishmanoid. PMID- 29008367 TI - An Epidemic of Anasarca in the North Andamans. PMID- 29008369 TI - Tennis Elbow. PMID- 29008370 TI - Diluted Phenol Injections in Hydrocele. PMID- 29008371 TI - A Note on a New Disease-"Dermal Leishmaniasis" (Brahmachari). PMID- 29008372 TI - The Leishmaniasis Problem. PMID- 29008373 TI - The Danger of Injecting Air into a Vein. PMID- 29008374 TI - Two Cases of Tropical Abscess of Liver Rupturing into the Abdomen. PMID- 29008375 TI - Accessory External Ear. PMID- 29008376 TI - The Indigenous Systems of Medicine. PMID- 29008378 TI - Current Topics. PMID- 29008377 TI - Correspondence. PMID- 29008379 TI - Service Notes. PMID- 29008380 TI - Short Notes on a Case of Rat-Bite Fever in Shillong. PMID- 29008381 TI - Electric-Ionisation and Nose Operations. PMID- 29008382 TI - Laboratory Records from Mesopotamia: No. III. Cholera. PMID- 29008383 TI - Correspondence. PMID- 29008384 TI - Note on the Weight Curve of the Normal Indian Infant: During the First Year. PMID- 29008385 TI - Indian Science Congress 1922: Medical Research Section. PMID- 29008387 TI - A Case of "Langri's Finger". PMID- 29008386 TI - The Therapeutics of Emetine. PMID- 29008388 TI - Acute "Kodon" Poisoning. PMID- 29008389 TI - An Investigation into the Causation of Lathyrism in Man. PMID- 29008390 TI - Intravenous Quinine in Malaria. PMID- 29008391 TI - The Value of Culture of the Peripheral Blood in Kala-Azar as a Diagnostic Procedure. PMID- 29008392 TI - Removal of the Tonsils. PMID- 29008393 TI - The Value of the Formolgel Test for Syphilis. PMID- 29008395 TI - Service Notes. PMID- 29008394 TI - Extraction of the Lens in Its Capsule. PMID- 29008396 TI - Correspondence. PMID- 29008398 TI - The Use and Abuse of Vaccine Therapy. PMID- 29008397 TI - A Case of Abnormal Labour, (Hydrothorax and Ascites in the Foetus). PMID- 29008399 TI - Observations on "Ulcus Tropicum" in North Palestine. PMID- 29008401 TI - A Case of Multiple Haemorrhages. PMID- 29008400 TI - Remarks on the Typhus Fever of Kumaon and on the Suggestion That It Is Transmitted by a Tick. PMID- 29008402 TI - A Case of Large Ovarian Cyst. PMID- 29008403 TI - Note on the Relative Rate of Absorption of Solar Radiant Heat of Silt Laden Waters. PMID- 29008404 TI - Filariasis at Puri. PMID- 29008405 TI - Correspondence. PMID- 29008406 TI - Primary Carcinoma of the Liver. PMID- 29008407 TI - Carbon Tetrachloride in Helminthiasis: A Preliminary Note. PMID- 29008408 TI - The Late Sir Patrick Manson : Then and Now. PMID- 29008409 TI - Some Contra-Indications to the Intra-Capsular Operation for Cataract, Based on 8,000 Cases by an Intra-Capsular Operator. PMID- 29008411 TI - Current Topics. PMID- 29008410 TI - Medical Education in the United States and in India. PMID- 29008412 TI - Service Notes. PMID- 29008414 TI - The Sir Walter Buchanan Scholarship at Epsom College. PMID- 29008413 TI - Toxic Jaundice of Unknown Origin in the Andamans. PMID- 29008415 TI - Post-Mortem Examination in Cerebral Malaria: A New and Simple Method of Demonstrating Parasites in the Capillaries of the Brain. PMID- 29008416 TI - An Analysis of the Clinical Picture in Kala-Azar: Part I. PMID- 29008417 TI - The Role of Poisonous Amines. PMID- 29008418 TI - The Therapeutics of the Cinchona Alkaloids: Part I. PMID- 29008420 TI - The Production and Pharmacological Action of Khesari Amine. PMID- 29008419 TI - British Income Tax. PMID- 29008421 TI - A Case of Salivary Calculus. PMID- 29008422 TI - A Case of Oxyuris Vermicularis in the Vermiform Appendix. PMID- 29008423 TI - Correction. AB - [This corrects the article on p. 366 in vol. 57.]. PMID- 29008424 TI - The Care of Women and Children in Indian Industries. PMID- 29008425 TI - Service Notes. PMID- 29008427 TI - Current Topics. PMID- 29008426 TI - The Therapeutics of Digitalis. PMID- 29008429 TI - Notes on Drugs: The Modern Treatment of Leprosy. PMID- 29008428 TI - Notes on a Case of Bronchomoniliasis. PMID- 29008430 TI - The Recent Epidemic in Lucknow: So-Called Cholera. PMID- 29008431 TI - A Case of Gumma of the Vertebrae. PMID- 29008432 TI - Clinical Pictures of Tuberculosis in Relation to Bones and Joints. PMID- 29008434 TI - Kerosine Oil in Asthma. PMID- 29008433 TI - A Case of Vaginal Tumour of Unusual Size. PMID- 29008436 TI - Current Topics. PMID- 29008437 TI - The New Year. PMID- 29008435 TI - An Unusual Case of Snake-Bite. PMID- 29008438 TI - Kala-Azar : A Preliminary Note on the Treatment by the Intramuscular Injection of a Special Preparation of Sodium Antimonyl Tartrate. PMID- 29008439 TI - A Choleroid Epidemic in the United Provinces: With Pathological Account. PMID- 29008440 TI - Snake-Bite in India. PMID- 29008441 TI - Service Notes. PMID- 29008442 TI - Statistics of the Treatment of Cholera Cases by a Modified Method of Sir Leonard Rogers, as Carried on at the Mayo Hospital. PMID- 29008444 TI - Need of Dental Colleges in India. PMID- 29008443 TI - The Danger of Injecting Air into a Vein. PMID- 29008445 TI - A Case of Double Facial Paralysis Following Syphilis. PMID- 29008446 TI - Use of Tincture Iodine Intravenously. PMID- 29008447 TI - Correspondence. PMID- 29008448 TI - Rhinosporidium Kinealyi of the Conjunctiva. PMID- 29008449 TI - The Role of Cattle in the Epidemiology of Malaria. PMID- 29008451 TI - The Economic Factor in Tropical Diseases. PMID- 29008450 TI - Some Economic Aspects of Bengal Malaria. PMID- 29008452 TI - Flavine as a Therapeutic Agent. PMID- 29008453 TI - Service Notes. PMID- 29008454 TI - The Causation of Epidemic Dropsy. PMID- 29008455 TI - Cataract Extraction with Iridotomy. PMID- 29008457 TI - A Case of Retro-Peritonial Haemorrhage. PMID- 29008456 TI - Our Hospitals and Dispensaries. PMID- 29008458 TI - Current Topics. PMID- 29008459 TI - The Bombay School of Tropical Medicine. PMID- 29008460 TI - The Problem of Kala-Azar. PMID- 29008461 TI - Surgical Aspects of Amoebiasis: Amoebae: Their Character and Pathogenicity. PMID- 29008462 TI - A Case of Liver Abscess Which Had Ruptured into the Abdominal Cavity. PMID- 29008463 TI - The Price of Quinidine. PMID- 29008464 TI - Scabies? PMID- 29008465 TI - A Case of Congenital Hydronephrosis. PMID- 29008467 TI - The Epidemic Dropsy of Bengal. A Problem Solved. PMID- 29008466 TI - The Blood Count in Ankylostomiasis. A Warning. PMID- 29008468 TI - Cinchona Febrifuge in Malaria. PMID- 29008469 TI - A Note on the Use of E. C.: Electrolytic Chlorogen. PMID- 29008470 TI - Electrolytic Chlorogen. PMID- 29008471 TI - Expression versus Capsulotomy. PMID- 29008472 TI - A Plea for the More Common Use of Lumbar Puncture. PMID- 29008474 TI - Combretum Pilosum Roxb. as an Anthelmintic for Ascaris Lumbricoides. PMID- 29008473 TI - Gleanings from the Records of the Government Maternity Hospital, Madras. PMID- 29008475 TI - The Situation of the Malarial Parasite in Relation to the Red Blood Corpuscle. PMID- 29008476 TI - A Comparison of E. C. Bleach, and Chlorogen. PMID- 29008477 TI - The Prevalence of Ileocaecal Kinks in Appendicitis. PMID- 29008478 TI - Service Notes. PMID- 29008479 TI - Some Interesting "Eye Cases". PMID- 29008480 TI - Current Topics. PMID- 29008481 TI - Drainage in Abdominal Emergencies. PMID- 29008482 TI - The Advantages of a Single Infection. PMID- 29008483 TI - A Case of Echinococcal Infection of the Eyeball. PMID- 29008484 TI - E. C. PMID- 29008485 TI - A Case of Sarcoma of the Knee. PMID- 29008486 TI - A Case of Breech Presentation. PMID- 29008487 TI - Correspondence. PMID- 29008488 TI - An Analysis of 336 Cases of Hydrocele and Haematocele in Which Operation for Radical Cure Was Performed. PMID- 29008489 TI - Treatment of Malaria in Pregnancy. PMID- 29008490 TI - Is Human Hydrophobia Infective? PMID- 29008491 TI - Pathogenicity of Spirilla in the Sputum. PMID- 29008492 TI - The Natural Cure and Prevention of Dysentery. PMID- 29008493 TI - Tonsillectomy: A Simple Method Used in 840 Cases. PMID- 29008494 TI - Treatment of Oriental Sore. PMID- 29008495 TI - Service Notes. PMID- 29008496 TI - Literary Notes. PMID- 29008497 TI - Midwifery Mechanics. PMID- 29008498 TI - A Case of Mauling by a Leopard. PMID- 29008500 TI - Correspondence. PMID- 29008499 TI - A Case of Tri-Orchid. PMID- 29008501 TI - Current Topics. PMID- 29008502 TI - Hibernating Mosquitoes as Carriers of Malaria. PMID- 29008503 TI - A Case of Suprapublic Cystomy Complicated with Typholumbricosis. PMID- 29008504 TI - Correspondence. PMID- 29008506 TI - Correspondence. PMID- 29008505 TI - An Outbreak of Epidemic Dropsy at Malda Jail. PMID- 29008508 TI - The Indian Medical Service. PMID- 29008507 TI - An Antiseptic and Anaesthetic Catheter Oil. PMID- 29008509 TI - Physiological Notes. PMID- 29008510 TI - Tuberculous Glands in Axilla. PMID- 29008511 TI - Treatment of Purpura Haemorrhagica. PMID- 29008512 TI - Service Notes. PMID- 29008513 TI - "Medical" Advertisements in the Indian Press. PMID- 29008514 TI - The Duties and Responsibilities of Students and Practitioners of Medicine. PMID- 29008515 TI - The Etiology and Treatment of Pyorrhea Alveolaria. PMID- 29008516 TI - Flavine in Ophthalmic Practice. PMID- 29008517 TI - A Short Report on the Treatment of Plague by the Solution of Iodine and Camphor. PMID- 29008518 TI - Elephantiasis Scroti-Weighing 36 Lb. PMID- 29008519 TI - Current Topics. PMID- 29008520 TI - Notes on Certain Cases of Fever. PMID- 29008521 TI - Two Cases of Abdominal Hydatid Cysts. PMID- 29008522 TI - Human Bites. PMID- 29008523 TI - A Plea to Ligate the Hydrocele Sac with Living Tissue. PMID- 29008524 TI - Correspondence. PMID- 29008525 TI - Unqualified Practitioners. PMID- 29008526 TI - The Management of a Drug Godown in India. PMID- 29008527 TI - Transverse Inguinal versus Vertical Scrotal Incision in the Operation for Radical Cure of Hydrocele. PMID- 29008528 TI - Bogus Diplomas. PMID- 29008529 TI - Dreams. PMID- 29008531 TI - Service Notes. PMID- 29008530 TI - Preliminary Note on the Treatment of Tubercular Affections of the Enclosed Cavities Abscesses, and Caries, by Inflation with Oxygen. PMID- 29008532 TI - An Analysis of over 500 Cases of Genital Chancre in the Native Male. PMID- 29008534 TI - Physiological Notes. PMID- 29008533 TI - Notes on Novarsenobillon. PMID- 29008536 TI - Literary Notes. PMID- 29008535 TI - Current Topics. PMID- 29008538 TI - A Case of Tropical Sore Cured by Intravenous Injections of Tartar Emetic. PMID- 29008537 TI - Treatment of Cerebrospinal Meningitis by Spinal Irrigation with Electrargol. PMID- 29008539 TI - A Kidney with Large Stone and Hydronephrosis Weighing 12 Ounces. PMID- 29008540 TI - Encephalitis Lethargica: A Clinical Lecture. PMID- 29008541 TI - Midwifery Mechanics. PMID- 29008542 TI - Organo-Therapeutic Treatment of Malaria. PMID- 29008543 TI - Observations on the Treatment of Hookworm Disease. PMID- 29008544 TI - The Superfluous Woman. PMID- 29008546 TI - Current Topics. PMID- 29008545 TI - Electricity and Medicine. PMID- 29008547 TI - A Note on Vaccine Therapy in Typhoid and Paratyphoid Fever. PMID- 29008549 TI - Correspondence. PMID- 29008548 TI - A Case of Penetrating Abdominal Wound. PMID- 29008550 TI - Correspondence. PMID- 29008551 TI - Sodium Morrhuate and Sodium Hydnocarpate in Leprosy. PMID- 29008552 TI - Hazaribagh: A Popular Health Resort. PMID- 29008553 TI - Note on a Case of Hydrophobia. PMID- 29008554 TI - Correspondence. PMID- 29008556 TI - Service Notes. PMID- 29008555 TI - Bacteriological Investigation of Normal and Diseased Eyes. PMID- 29008557 TI - A Case of Melancholic Stupor (Psychocoma). PMID- 29008559 TI - Calcutta School of Tropical Medicine: The Darbhanga Medical Research Scholarship. PMID- 29008558 TI - Report on a Large Lipoma in a Child. PMID- 29008560 TI - Correspondence. PMID- 29008562 TI - Gastric Ulcer. PMID- 29008561 TI - Correspondence. PMID- 29008563 TI - Literary Notes. PMID- 29008564 TI - Influenza. PMID- 29008565 TI - Correspondence. PMID- 29008566 TI - Removal of Filaria from under the Conjunctiva. PMID- 29008567 TI - Note on Mr. Charles' Specimen. PMID- 29008568 TI - A Newer Interpretation of the Pathogenesis, Prophylaxis and Treatment of Influenza. PMID- 29008569 TI - Surgical Tuberculosis. PMID- 29008571 TI - A Two-Ounce Stone in the Urethra. PMID- 29008570 TI - Service Notes. PMID- 29008572 TI - A Preliminary Report on the Minimum Curative Dose of Quinine in the Treatment of Malarial Fever by the Intravenous Method. PMID- 29008573 TI - Current Topics. PMID- 29008574 TI - Preliminary Note on the Treatment of Leprosy by Antimony. PMID- 29008575 TI - Correspondence. PMID- 29008576 TI - Physiological Notes. PMID- 29008577 TI - Functional Aphonia in a Case of Homicidal Cut-Throat. PMID- 29008579 TI - Literary Notes. PMID- 29008578 TI - London School of Tropical Medicine Examination Result. 63rd Session, May-July, 1920. PMID- 29008580 TI - Notes on Field Ambulance Organisation. PMID- 29008582 TI - Case of Intolerance to Aspirin. PMID- 29008581 TI - Treatment of Pregnant Females Suffering from Malarial Fever. PMID- 29008583 TI - Some Observations on Blood Pressure during Intravenous Injection of Quinine in the Treatment of Malarial Fever. PMID- 29008585 TI - A Case of Acute Catarrhal Jaundice. PMID- 29008586 TI - Post-Graduate Instruction in Veneral Diseases. PMID- 29008584 TI - Correspondence. PMID- 29008587 TI - The Prevalence in India of Gastric and Duodenal Ulcer and Allied Conditions of the Upper Abdomen with Some Observations of the Diagnosis and Treatment. PMID- 29008588 TI - Cutaneous Myiasis in Man and Animals in India. PMID- 29008590 TI - Medical Requirements of Aeronauts. PMID- 29008589 TI - Current Topics. PMID- 29008591 TI - Service Notes. PMID- 29008592 TI - Physiological Notes. PMID- 29008594 TI - Service Notes. PMID- 29008593 TI - Some Further Observations on Rupture of the Spleen. PMID- 29008595 TI - An Indian Creche in Bangalore. PMID- 29008597 TI - The Treatment of Cerebro-Spinal Syphilis by Means of Sero-Arsenous and Mercuric Iodide. PMID- 29008596 TI - Lathyrism. PMID- 29008598 TI - Note on Intravenous Injections of Tartar Emetic in the Treatment of Malaria. PMID- 29008599 TI - Quinine in Malarial Prophylaxis. PMID- 29008600 TI - Current Topics. PMID- 29008601 TI - The Effect of Radishes in Dropsy. PMID- 29008602 TI - Development of the Round Worm. PMID- 29008604 TI - Chlorination of Drinking Water Supplies in the Field. PMID- 29008603 TI - Tobacco Fleas and Plague. PMID- 29008605 TI - Medical and Surgical Notes (London Mission Hospital). PMID- 29008606 TI - A Case of Calculous Pyonephrosis. PMID- 29008607 TI - Sodium Gynocardate and Sodium Morrhuate in Tubercular Disease. PMID- 29008608 TI - Some Unusual Methods of Disposal of Excreta in Camps. PMID- 29008609 TI - The Laying out of a Large Military Camp. PMID- 29008610 TI - Current Topics. PMID- 29008611 TI - Treatment of Oriental Sore. PMID- 29008612 TI - Four Years' Further Experience of Autogenous Oral Streptococcal Vaccines in the Treatment of Seventeen Cases of Sprue. PMID- 29008613 TI - Bombay Medical Council: February Session 1918. PMID- 29008615 TI - Service Notes. PMID- 29008614 TI - The British Medical Association and the I. M. S. PMID- 29008616 TI - Non-Operative Treatment of Carbuncles and Boils. PMID- 29008617 TI - The Prevention and Treatment of Malaria. PMID- 29008618 TI - Case of Toxaemic Jaundice. PMID- 29008619 TI - The Injection of Lymph as a Protector against Small-Pox. PMID- 29008621 TI - Indian Medical Service: Memorandum on Its Present Position and the Reforms Necessary. PMID- 29008620 TI - How to Examine Recruits. PMID- 29008622 TI - The Prevention of Malaria in Cantonments. PMID- 29008623 TI - The Present Position of the Treatment of Syphilis. PMID- 29008624 TI - A Snake-Bite (Cobra) Case. PMID- 29008625 TI - Rat Destruction as a Means for the Prevention of Plague. PMID- 29008626 TI - A Case of Gangosa at the Alipore Jail. PMID- 29008627 TI - Sodium Antimonyl Tartrate in Kala-Azar. PMID- 29008628 TI - Constipation in Malaria. PMID- 29008629 TI - Destruction of Rats and Prevention of Plague. PMID- 29008631 TI - Tetanus and Technique. PMID- 29008630 TI - War Surgery in an Indian General Hospital in Mesopotamia. PMID- 29008632 TI - A Public Health Journal. PMID- 29008633 TI - A Case of Bilharzia Infection: Imported from Mesopotamia, and Occuring in the Civil Population at Karachi. PMID- 29008634 TI - Current Topics. PMID- 29008635 TI - Sodium Cacodylate in Malaria. PMID- 29008637 TI - Relapsing Fever. PMID- 29008636 TI - Fleas and Plague. PMID- 29008638 TI - Blindness in India. PMID- 29008639 TI - Service Notes. PMID- 29008641 TI - Salines in Cholera. PMID- 29008640 TI - The Haemoglobin Index in Coolies. PMID- 29008642 TI - The Metals Gold, Silver, and Arsenic in the Colloid State. PMID- 29008644 TI - A Ministry of Health. PMID- 29008643 TI - Detection of Hookworm Eggs. PMID- 29008645 TI - Urea Hydrochloride. PMID- 29008646 TI - Urea Hydrochloride. PMID- 29008647 TI - Report on Treatment of Thirty Lepers with Sodium Gynecardate "A". PMID- 29008649 TI - Current Topics. PMID- 29008648 TI - The Metamorphosis and Standardization of the L. M. P. PMID- 29008650 TI - A Case of Sacculation of the Bladder Containing a Dumb-Bell-Shaped Calculus. PMID- 29008652 TI - Tropical Australia. PMID- 29008651 TI - Bite from Echis Carinata : Recovery. PMID- 29008653 TI - Quinine Urea Hydrochloride. PMID- 29008654 TI - A Case of Syphilitic Fever. PMID- 29008655 TI - Lathyrism-Like Disease (Due to Bajra). PMID- 29008656 TI - Service Notes. PMID- 29008657 TI - Surgical Notes. PMID- 29008658 TI - Some New Principles in Nutrition. PMID- 29008659 TI - Stomatitis and Scrotal Eczema. PMID- 29008660 TI - Forgotten Pages of Jail History. PMID- 29008662 TI - The Prevention of Scurvy and Beri-Beri. PMID- 29008663 TI - Ayurvedic Medicine. PMID- 29008661 TI - On the Importance of Some Minor Eye Operations. PMID- 29008664 TI - Natural Painless Child-Birth. PMID- 29008665 TI - Intramuscular Injections of Sodium Gynocardate in Leprosy. PMID- 29008666 TI - The Life of Lord Lister. PMID- 29008667 TI - Current Topics. PMID- 29008668 TI - Service Notes. PMID- 29008670 TI - Stomatitis and Scrotal Eczema. PMID- 29008669 TI - The Sir Pardey Lukis Memorial Fund. PMID- 29008671 TI - Destruction of Rats as a Means for the Prevention of Plague. PMID- 29008672 TI - Hospital Building in India. PMID- 29008673 TI - The Susruta Samhita. PMID- 29008675 TI - Two Surgical Cases. PMID- 29008674 TI - Intramuscular Injections of Quinine. PMID- 29008676 TI - A Medico-Legal Question. PMID- 29008678 TI - Current Topics. PMID- 29008677 TI - Quinine and Urea Hydrochloride Hypodermically. PMID- 29008680 TI - Sodium Gynocardate in Leprosy. PMID- 29008679 TI - Service Notes. PMID- 29008681 TI - Recurrent Dislocation of Shoulder. PMID- 29008683 TI - Sir Pardey Lukis Memorial Committee. PMID- 29008682 TI - Case of Carotid Aneurism. PMID- 29008684 TI - Case of Cerebro-Spinal Fever. PMID- 29008685 TI - A Case of Actinomycotic Pleuro Mediastinitis. PMID- 29008687 TI - Observations on Three Cases of Actinomycosis Hominis. PMID- 29008686 TI - Destruction of Rats as a Means for the Prevention of Plague. PMID- 29008688 TI - Family Epidemic of Scarlet Fever. PMID- 29008689 TI - Annus Medicus. PMID- 29008690 TI - Another "New" Operation for Cataract. PMID- 29008691 TI - Rectal Anaesthesia. (Report of 82 Cases). PMID- 29008692 TI - Quinoidine. PMID- 29008693 TI - Adulteration of Quinine. PMID- 29008694 TI - Serums. PMID- 29008696 TI - Notes on Current Topics. PMID- 29008695 TI - Service and War Notes. PMID- 29008697 TI - Capacity of the Bladder of a Child: Two and a Half Months Old. PMID- 29008699 TI - Haemoglobinuria. PMID- 29008698 TI - A Glance at Blackwater Fever. PMID- 29008700 TI - A Case of Snake-Bite. PMID- 29008701 TI - Kala-Azar and Tartar Emetic. PMID- 29008702 TI - Quinoidine and Diarrhoea. PMID- 29008703 TI - Blunderbuss Therapy. PMID- 29008704 TI - An Extraordinary Case of Self-Mutilation. PMID- 29008705 TI - An Unusual Fracture. PMID- 29008706 TI - The Kurchi Treatment of Amoebic Dysentery. PMID- 29008707 TI - A Case of Agranulocytic Angina. PMID- 29008708 TI - Quinine "Addiction". PMID- 29008709 TI - The Value of Medical Societies. PMID- 29008711 TI - The Cholera Bacteriophage. PMID- 29008710 TI - Infection by a Gnathostome Simulating Mastoiditis. PMID- 29008713 TI - On the Role of Argas Persicus Oku, in the Transmission of Pasteurella Avicida. PMID- 29008712 TI - Scirrhus Cancer of the Breast in the Male. PMID- 29008714 TI - Enterococcus Bacteriaemia in Association with Infections with Bacillus Typhosus. PMID- 29008715 TI - Three Cases of Salivary Calculus. PMID- 29008717 TI - Notes on Current Topics. PMID- 29008716 TI - On the Relative Frequency of Supraclavicular and Infraclavicular Pulmonary Tuberculosis, and Its Bearing on the Prognosis of the Disease in India. PMID- 29008718 TI - Unusual Symptoms in a Case of Round-Worm Infection. PMID- 29008719 TI - Gynaecology and Tropical Diseases in Shakespeare. PMID- 29008720 TI - The Treatment of Acute Intestinal Obstruction. PMID- 29008721 TI - Some Observations on the Preparation and Examination of Thick Films for Malaria Parasites. PMID- 29008722 TI - A Case of Amoebic Abscess of Liver. PMID- 29008723 TI - Angioma, Treatment by Diathermy. PMID- 29008724 TI - Studies in Untreated Malaria: I. A Case of Experimentally Induced Quartan Malaria. PMID- 29008725 TI - Medical News. PMID- 29008726 TI - Service Notes. PMID- 29008727 TI - On a Simple Solidified Haemoglobinised Saline Agar Medium Suitable for Surface Cultures of Leishmania and Allied Flagellates. PMID- 29008729 TI - Anti-Plague Vaccine in the Treatment of Plague. PMID- 29008728 TI - Petrol Dermatitis. PMID- 29008730 TI - A Case of Dentigerous Cyst: Follicular Odontome. PMID- 29008731 TI - The Use of a Standardised Preparation of the Total Alkaloids of Kurchi Bark in Amoebic Dysentery. PMID- 29008733 TI - The Effect of Radiation Therapy upon Mediastinal Tumours. PMID- 29008732 TI - A Simple Treatment for Naga Sores. PMID- 29008734 TI - The All-India Medical Licentiates' Association. PMID- 29008735 TI - Some Safeguards and Points of Technique in the Extraction of Senile Cataract with Capsulotomy. PMID- 29008736 TI - A Preliminary Report on the Suitability of Paris Green as an Anopheline Larvicide as Applied to Punjab Conditions. PMID- 29008737 TI - On Rheumatic Infection as a Cause of Mitral Stenosis Amongst Young Indians. PMID- 29008738 TI - Blunderbuss Therapy. PMID- 29008740 TI - Leeches in Cardiac Disease. PMID- 29008739 TI - Ars Gynaecologica. PMID- 29008741 TI - Centepeda Orbicularis. PMID- 29008742 TI - A Case of Germination of Teeth. PMID- 29008743 TI - A Test for Carbon Tetrachloride. PMID- 29008744 TI - Corrigendum. AB - [This corrects the article on p. 691 in vol. 64.]. PMID- 29008745 TI - Notes on Current Topics. PMID- 29008746 TI - Radium in India. PMID- 29008748 TI - A Case of Jarisch Herxheimer Phenomenon. PMID- 29008747 TI - Medical News. PMID- 29008749 TI - The Sterilisation of Hypodermic Syringes. PMID- 29008750 TI - Prolapsus Uteri. PMID- 29008751 TI - Service Notes. PMID- 29008752 TI - The Purity of Tube Well Waters. PMID- 29008753 TI - Keratolysis Plantare Sulcatum, a Lesion Due to an Actinomycotic Fungus. PMID- 29008754 TI - The Cholera Bacteriophage. PMID- 29008756 TI - Jungle and Malaria in Bengal. PMID- 29008755 TI - A Review of Our Present Knowledge of the Bacteriology and Pathology of Human Leprosy. PMID- 29008758 TI - Service Notes. PMID- 29008757 TI - Science versus Art in Medicine. PMID- 29008759 TI - Corrigendum. AB - [This corrects the article on p. 541 in vol. 65.]. PMID- 29008760 TI - Transient Glycosuria in a Comatose Patient. PMID- 29008761 TI - The Drugs Enquiry Committee, India, 1930. PMID- 29008762 TI - An Undiagnosed Malady. PMID- 29008763 TI - Early Infant Mortality in India with Special Reference to Premature Birth. PMID- 29008764 TI - Impressions of a Tour through Some Well-Known Medical Centres in Europe. PMID- 29008765 TI - Urobilinuria in Malaria. PMID- 29008766 TI - Narcosis in Childbirth. PMID- 29008767 TI - A Suggested Standard Treatment of Malaria Based upon the Results of the Controlled Investigation of over 3,700 Cases. PMID- 29008768 TI - Cancer of the Breast in a Man. PMID- 29008769 TI - Multiple Injuries to the Abdominal Viscera. PMID- 29008771 TI - Notes on Current Topics. PMID- 29008770 TI - Factors Which Determine the Differences in the Types of Lesions Produced by Filaria Bancrofti in India. PMID- 29008772 TI - Tetany in Children. PMID- 29008773 TI - Note on a Case of "Dermal Leishmanoid" from Madras. PMID- 29008774 TI - Is Medicine Fulfilling Its Responsibilities to Future Generations? A Plea for the Study of Eugenics. PMID- 29008775 TI - A Case of Epistaxis in Purpura. PMID- 29008776 TI - Records of Findings of Adult Wuchereria (Filaria) Bancrofti in India. PMID- 29008777 TI - Malaria at Kapurthala Dispensary, Lucknow. PMID- 29008778 TI - Congenital Bilateral Absence of the Radius and Thumb. PMID- 29008779 TI - Medical News. PMID- 29008781 TI - Some Aspects of the Ascaris Problem. PMID- 29008780 TI - A Case of Rhinolith. PMID- 29008783 TI - The Differential Diagnosis of Cholera and Food Poisoning. PMID- 29008782 TI - The Isolation of Atoxic Strains of Bacillus Tetani in Egypt. PMID- 29008784 TI - Accelerated Production of Specific Urinary Pigments by Drug Administration. I. Effect of Phenyldimethylpyrazolon on Urobilin Formation. PMID- 29008785 TI - A Case of Oxycephaly. PMID- 29008786 TI - An Experimental Study of Host Susceptibility to Cholera. PMID- 29008787 TI - The Prognostic Importance of the Widal Reaction in Typhoid Fever. PMID- 29008788 TI - Radium Therapy. A Summary of a Year's Work, with a Detailed Description of Some Cases. PMID- 29008789 TI - The Diagnosis of Kala-Azar by Culture of the Peripheral Blood. PMID- 29008790 TI - Notes on Current Topics. PMID- 29008792 TI - Service Notes. PMID- 29008791 TI - Intravenous Calcium Chloride in the Treatment of Cholera. PMID- 29008794 TI - Notes on Current Topics. PMID- 29008795 TI - The Science of Disease. PMID- 29008793 TI - The Purity of Tube Well Waters. PMID- 29008796 TI - Psittacosis. PMID- 29008797 TI - Milk Injections in Skin Diseases. PMID- 29008798 TI - Carbon Tetrachloride, Merck. PMID- 29008799 TI - A New Case of Bertiella Studeri in a Human Being. PMID- 29008800 TI - Aphonia after Quinine Administration. PMID- 29008801 TI - Liquid Extracts of Kurchi. PMID- 29008802 TI - A Case of Full Term Abdominal Pregnancy: Living Mother and Child. PMID- 29008803 TI - Protein Reactions of Bacteria: A Plea for Their Routine Use and Intensive Study. PMID- 29008804 TI - The Position of Psychology in the Teaching of Medicine. PMID- 29008805 TI - The Differential Diagnosis of Leprosy and Dermal Leishmaniasis. PMID- 29008806 TI - Some Cases of Surgery of the Hand. PMID- 29008807 TI - A Note on the Local Treatment of Leprous Ulcers. PMID- 29008808 TI - A Clinical Study of Post-Kala-Azar Dermal Leishmaniasis. PMID- 29008809 TI - Coconut Milk as an Anthelmintic. PMID- 29008810 TI - An Easily Improvised Apparatus for the Treatment of Fracture of the Femur. PMID- 29008811 TI - The Maternity Conditions of Women Mill-Workers in India. PMID- 29008812 TI - Cholera and Malaria. PMID- 29008813 TI - Medical News. PMID- 29008814 TI - Service Notes. PMID- 29008815 TI - A Note on an Apparatus Designed to Take Samples of Waters from Wells, Tanks, Etc., at Stated Depths. PMID- 29008816 TI - The Place of Non-Specific Protein Therapy in Gynaecology. PMID- 29008817 TI - Ars Obstetrica. PMID- 29008818 TI - The Value of the Antimony Test in the Diagnosis of Kala-Azar. Part II. The Finger Prick Blood Test. PMID- 29008819 TI - On the Advisability of a Routine Wassermann Reaction in Every Case of Diabetes Mellitus. PMID- 29008820 TI - Helminthic Infections in Shillong. PMID- 29008821 TI - Tannic Acid in the Treatment of Burns. PMID- 29008822 TI - Forecast of the Probable Major Variations in Cholera, Small-Pox and Plague in India during 1930, Based on the Meteorology of 1929. PMID- 29008823 TI - The Anopheles Stephensi Problem in Calcutta. PMID- 29008824 TI - Service Notes. PMID- 29008825 TI - Diabetes Mellitus in Children. PMID- 29008826 TI - Kurchi Extracts in Amoebiasis. PMID- 29008828 TI - A Note on the Use of Ultraviolet Rays in the Treatment of Leprosy. PMID- 29008829 TI - Nervous Symptoms Apparently Due to a Heavy Ascaris Infection. PMID- 29008827 TI - A Case of Meningocele. PMID- 29008830 TI - Some Notes on the Union of Epiphyses in Indian Girls. PMID- 29008832 TI - Notes on Current Topics. PMID- 29008831 TI - A Review of Some of the Work by Ophthalmologists in India in 1929. PMID- 29008834 TI - Medical News. PMID- 29008833 TI - Notes on Ulcus Tropicum in the Jharia Coalfieds in 1922. PMID- 29008835 TI - The Action of Emetine on Entamoeba Histolytica. PMID- 29008836 TI - A Case of Spotted Fever (Rocky Mountain Fever, Tick Fever or Typhus Fever). PMID- 29008837 TI - A Simple Method of Treating Salivary and Other Glandular Swellings. PMID- 29008838 TI - The Technique of Spinal Analgesia. PMID- 29008839 TI - Ulcus Tropicum in Kanara District. PMID- 29008840 TI - A Foreign Body in the Peri-Tonsillar Space. PMID- 29008841 TI - Contusion of the Eye and Commotio Retinae. PMID- 29008842 TI - Some Observations on the Incidence and Mortality from Eclampsia in Calcutta, and Its Prevention. PMID- 29008843 TI - Urticaria Due to Filarial Toxin. PMID- 29008844 TI - Gangrenous Stomatitis Following Dysentery. PMID- 29008846 TI - An Early Pioneer on the Study of Indian Malaria. PMID- 29008845 TI - A Case of Alkaptonuria. PMID- 29008847 TI - Some Surgical Aspects of Tuberculosis. PMID- 29008848 TI - The Effect of Sanocrysin on the Efficiency of the Liver. PMID- 29008850 TI - Service Notes. PMID- 29008849 TI - Notes on the Pathogenesis of Sprue and the Asthenic Diarrhoea of Indians: With Special Reference to the Role Played Therein by Amoebiasis. The Probable Identity of the Two Former Conditions, and Their Connection with Addisonian Anaemia Subacute Combined Degeneration of the Cord-Hunterian Glossitis Syndrome of Hurst. PMID- 29008851 TI - Mycetoma in Ramnad. PMID- 29008852 TI - The Significance of Spirochaetes in the Sputum, with Special Reference to Pulmonary Tuberculosis. PMID- 29008854 TI - Notes on Current Topics. PMID- 29008853 TI - Occupational Therapy. PMID- 29008855 TI - Some Observations on an Unusual Epidemic of Malaria in the City of Lucknow (April September 1929). PMID- 29008856 TI - Volvulus of the Small Intestine. PMID- 29008857 TI - The Treatment of Malaria. PMID- 29008858 TI - The Value of Phrenic-Exairesis in the Treatment of Pulmonary Tuberculosis. PMID- 29008859 TI - Cholera in a Khasi Village and Its Treatment with Bacteriophage. PMID- 29008860 TI - Medical News. PMID- 29008861 TI - Filarial Periodicity. PMID- 29008862 TI - Anti-Rabic Policy in India. PMID- 29008863 TI - An Epidemic in Rats. PMID- 29008864 TI - The Organism of Bovine Lymphangitis. PMID- 29008865 TI - A New and Simple Treatment for Intestinal Tuberculosis, Introduced by M. McConkey. PMID- 29008867 TI - The Treatment of Malaria. PMID- 29008866 TI - Death from Compressed-Air Sickness in India. PMID- 29008869 TI - Notes on Current Topics. PMID- 29008868 TI - Retention of a Dead Ectopic Foetus. PMID- 29008870 TI - Sliding Hernia. PMID- 29008872 TI - Syphilis in Madras. PMID- 29008871 TI - A Comparison of the Wassermann and Kahn Tests in 200 Cases. PMID- 29008873 TI - Is Public Health Worth While?: An Address Delivered on the 29th April, 1930, to the Rotary Club, Rangoon. PMID- 29008874 TI - Medical News. PMID- 29008875 TI - Some Interesting Cases. PMID- 29008876 TI - Health Education-A Device. PMID- 29008877 TI - Errors of Refraction. PMID- 29008878 TI - Five Years' Anti-Malaria Measures on the Travancore Tea Companies' Estates. PMID- 29008879 TI - The Treatment of Oriental Sore with Berberine Acid Sulphate. PMID- 29008880 TI - Corrigendum. AB - [This corrects the article on p. 467 in vol. 65.]. PMID- 29008882 TI - The Causation of Cancer. PMID- 29008881 TI - The Arterial Supply of the Appendix: From the Department of Anatomy, University Medical College, Mysore. PMID- 29008884 TI - Malaria Control. PMID- 29008883 TI - A Case of Hydrophobia. PMID- 29008885 TI - A Plea for More Confidence in the Peritoneum. PMID- 29008887 TI - Service Notes. PMID- 29008886 TI - Some Difficulties in the Diagnosis of Inguinal Hernia. PMID- 29008888 TI - Novasurol in the Treatment of Ascites. PMID- 29008889 TI - Intravenous Quinine. PMID- 29008890 TI - A Case of Syringomyelia. PMID- 29008891 TI - A Note on the Microscopical Examination of Faeces. PMID- 29008892 TI - "Honeycomb" Infection of the Hands and Feet. PMID- 29008893 TI - Antityphoid Inoculation. PMID- 29008894 TI - (1) Milk Injections in Asthma (2) Symptoms Due to Ascaris. PMID- 29008896 TI - Notes on Current Topics. PMID- 29008895 TI - The Causation of Lymph-Scrotum. PMID- 29008897 TI - The Use of a Snare in Enucleation of the Eyeball. PMID- 29008898 TI - A Difference of Opinion. PMID- 29008899 TI - A Myopia-Preventing Device. PMID- 29008900 TI - Erratum: A Study of Yaws in Khetri Area, Kamrup, Assam. AB - [This corrects the article on p. 421 in vol. 65.]. PMID- 29008901 TI - The Incidence of Sprue Amongst Indians. PMID- 29008902 TI - Psittacosis or Typhoid Fever? PMID- 29008903 TI - Results of Inoculation of Cholera Vaccine in Nabadwip (Bengal). PMID- 29008904 TI - Report on an Investigation of Beriberi at Guntur. PMID- 29008905 TI - An Unusual Case of Prolapse of the Uterus. PMID- 29008906 TI - Malaria in Bombay. PMID- 29008907 TI - Service Notes. PMID- 29008908 TI - Emetine in Bacillary Dysentery. PMID- 29008909 TI - Report of a Second Case of "Dermal Leishmanoid" from Madras. PMID- 29008910 TI - A Report on the 2nd International Congress on Malaria, Held at Algiers, 19th to 27th May, 1930. PMID- 29008911 TI - Medical News. PMID- 29008912 TI - A Case of Scurvy. PMID- 29008913 TI - Myiasis of Carious Teeth. PMID- 29008914 TI - A Case of Congenital Sacral Teratoma. PMID- 29008916 TI - A Case of Dermal Leishmaniasis Mistaken for Leprosy. PMID- 29008915 TI - Cardiovascular Manifestations of Epidemic Dropsy and Their Treatment. PMID- 29008917 TI - Ulcus Tropicum. PMID- 29008919 TI - The Remote Effects of Nasal Sinus Infections. PMID- 29008918 TI - The So-Called "Swallowed" Foreign Body. PMID- 29008920 TI - Experiments on the Vitamin B (Anti-Neuritic Factor) in Parched Rice; on Honey; and the Mucous Secretion of the Pigeon's Mouth. PMID- 29008921 TI - A Case of Highly Abnormal Blood Group Associated with Auto-Agglutination in the Cold. PMID- 29008923 TI - Ars Obstetrica. PMID- 29008922 TI - The Age of Consent Act. PMID- 29008924 TI - The Evolution of Medical Protozoology. PMID- 29008925 TI - The Uses and Abuses of Vaccines. PMID- 29008926 TI - Volvulus of the Small Intestine. PMID- 29008927 TI - Cardiospasm. PMID- 29008929 TI - Service Notes. PMID- 29008928 TI - A Case of Pneumonia Treated by "Pneumococcus Immunogen (Combined)". PMID- 29008930 TI - Medical News. PMID- 29008931 TI - A Case of Blackwater Fever. PMID- 29008933 TI - Notes on Current Topics. PMID- 29008932 TI - A Case of Fracture-Dislocation Carpal Scaphoid (Navicular). PMID- 29008934 TI - Bilateral Torticollis. PMID- 29008935 TI - A Severe Case of Osteomalacia. PMID- 29008936 TI - The Surgery of Tuberculosis of the Ileo-Caecal Region. PMID- 29008937 TI - Framboesia Tropica in Bengal. PMID- 29008939 TI - Aphonia Follow Quinine Administration. PMID- 29008938 TI - An Account of a Brief Tour with the Malaria Commission of the League of Nations. PMID- 29008940 TI - Undescended Testis as a Cause of Physical Rejection. PMID- 29008941 TI - "Naga" Sore in Rajputana. PMID- 29008942 TI - The Food Value of the Nut of Anacardium Occidentale (Hijli Badam). PMID- 29008943 TI - Marriage Festivals and the Spread of Cholera. PMID- 29008944 TI - Elimination of Uric Acid Via the Skin. PMID- 29008945 TI - Erratum: Psittacosis. AB - [This corrects the article on p. 277 in vol. 65.]. PMID- 29008947 TI - The Infectivity of Malaria Carriers. PMID- 29008946 TI - Foreign Body in the Ear a Cause of Persistent Hiccough. PMID- 29008948 TI - A Case of "Scurvy". PMID- 29008949 TI - An Unusual Abdominal Tumour. PMID- 29008950 TI - Ganglion-Like Swellings in Leprosy. PMID- 29008951 TI - Two Cases of Pneumonia with Thrombosis in the Brain, Having a Bearing on the Pathogenesis of Remote Pneumococcal Complications in Pneumonia. PMID- 29008952 TI - Plantago Ovata-Ispaghul-In Chronic Diarrhoeas and Dysenteries. PMID- 29008954 TI - Service Notes. PMID- 29008953 TI - Multiple Melanomata of the Iris. PMID- 29008955 TI - Notes on the Treatment of Varicose Veins by Sclerosing Injections. PMID- 29008956 TI - A Case of Probable Post-Vaccinal Encephalitis. PMID- 29008957 TI - Medical News. PMID- 29008958 TI - A Note on the Action of Ephedrine on Temperature. PMID- 29008959 TI - Transient Glycosuria of Doubtful Origin. PMID- 29008961 TI - Erratum: A Clinical Study of Post-Kala-Azar Dermal Leishmaniasis. AB - [This corrects the article on p. 249 in vol. 65.]. PMID- 29008960 TI - Note on the Occurrence of Jaundice in a Tuberculous Patient during Sanocrysin Treatment. PMID- 29008962 TI - A Note on Cancer and Radium in South India: Being Part of the Annual Report of the Madras Government General Hospital, 1929. PMID- 29008963 TI - A Case of Myiasis of the Nasal Fossa. PMID- 29008964 TI - A Case of Latent Typhoid Fever. PMID- 29008965 TI - A Study of Yaws in Khetri Area, Kamrup, Assam. PMID- 29008967 TI - Notes on Current Topics. PMID- 29008966 TI - Caudal Block. PMID- 29008968 TI - A Case of Pellagra. PMID- 29008969 TI - A Case of Trephining of Skull. PMID- 29008970 TI - Three Cases of Toxaemia Due to Ascariasis. PMID- 29008971 TI - Erratum: The Evolution of Medical Protozoology. AB - [This corrects the article on p. 23 in vol. 65.]. PMID- 29008972 TI - A Possible Pitfall in Making Leucocyte Counts. PMID- 29008973 TI - Bacteriophage in Its Clinical Aspect. PMID- 29008974 TI - Anaphylactic Shock after Milk Injection. PMID- 29008975 TI - Chopra's Antimony Test in a Non-Endemic Kala-Azar Area. PMID- 29008976 TI - A Case of Meningocele. PMID- 29008977 TI - "Beriberi" in Cheduba Island, Arakan, Burma. PMID- 29008978 TI - A Plea for More Confidence in the Peritoneum. PMID- 29008979 TI - The Failure of the Alkaloids of Holarrhena Antidysenterica (Kurchi) in the Treatment of Amoebic Hepatitis. PMID- 29008980 TI - The Care of the Electrocardiograph in the Tropics. PMID- 29008982 TI - Medical News. PMID- 29008981 TI - Urobilinuria and Its Importance in Malaria. PMID- 29008983 TI - Notes on Current Topics. PMID- 29008984 TI - The Treatment of Ulcus Tropicum. PMID- 29008985 TI - Studies in the Anopheline Fauna and Malaria of Bhagalpur (Bihar and Orissa). PMID- 29008986 TI - Service Notes. PMID- 29008987 TI - The Parasitology of Malaria in the Darjeeling Terai. PMID- 29008988 TI - Short Term Fevers in the Punjab. PMID- 29008989 TI - Intravenous Quinine in Malaria. PMID- 29008990 TI - A Preliminary Note on Addiction to "Post" (Unlanced Capsules of Papaver Somniferum). PMID- 29008991 TI - Restoration of the Conjunctival Cul-de-Sac in a Case of Extensive Posterior Symblepharon. PMID- 29008992 TI - The Bacteriological Findings in the Chlorinated Water Supply of a Large City in the Tropics. PMID- 29008993 TI - "Wets" versus "Drys". PMID- 29008994 TI - The Treatment of Post-Kala-Azar Dermal Leishmaniasis. PMID- 29008995 TI - The Present Position of Hookworm Treatment. PMID- 29008996 TI - Erratum: Centepeda Orbicularis. AB - [This corrects the article on p. 75 in vol. 65.]. PMID- 29008997 TI - "Appendix" in Relation to Inguinal Hernia and a Note on Local Anaesthesia. PMID- 29008998 TI - Studies on the Hydrogen Ion Concentration of Saliva. PMID- 29009000 TI - Spontaneous Pneumothorax. PMID- 29008999 TI - A Fatal Case of Chronic Interstitial Nephritis with Very High Blood Urea. PMID- 29009001 TI - Abstracts from Reports. PMID- 29009002 TI - Naga Sore in Rajkot (Kathiawar). PMID- 29009003 TI - Further Clinical Observations on Post-Kala-Azar Dermal Leishmaniasis. PMID- 29009004 TI - Medical News. PMID- 29009005 TI - A Case of Aplastic Anaemia. PMID- 29009006 TI - Service Notes. PMID- 29009008 TI - Current Topics. PMID- 29009007 TI - Treatment of Chronic Intestinal Amoebiasis with Gavano, a Derivative of Ipecacuanha. PMID- 29009009 TI - The Therapeutics of Malaria. PMID- 29009010 TI - Fracture Equipment: With Notes on Its Use. PMID- 29009011 TI - Observations on a Case of Coccidial Infection in Man (Isospora Belli Wenyon, 1923). PMID- 29009012 TI - Treatment of Myiasis. PMID- 29009013 TI - The Acid and Sanitol Treatment of the Intestinal Fluxes. PMID- 29009015 TI - Abstracts from Reports. PMID- 29009014 TI - Observations on the Normal Dietary of Infants and Children in Vizagapatam. PMID- 29009016 TI - Service Notes. PMID- 29009018 TI - Medical News. PMID- 29009017 TI - Latent Malaria Infection in Monkeys. PMID- 29009019 TI - Roundworms Causing Intestinal Obstruction. PMID- 29009020 TI - On the Concentration of Quinine in the Blood after Intravenous and Intramuscular Injections. PMID- 29009021 TI - Lymphadenitis of the Retroperitoneal Glands Simulating Appendicitis. PMID- 29009022 TI - Streptococcal Septicaemia and Filarial Orchitis. PMID- 29009023 TI - Current Topics. PMID- 29009025 TI - Intravenous Quinine Therapy in Malaria. PMID- 29009024 TI - An Allergic Manifestation. PMID- 29009027 TI - Quinine in the Therapeutics of Malaria. PMID- 29009026 TI - A Case of Enteric Fever. PMID- 29009028 TI - Two Cases of Peripheral Neuritis Treated by Intravenous Injections of Sodium Iodide. PMID- 29009029 TI - Filarial Affections of the Male Genital Tracts. PMID- 29009031 TI - Intravenous versus Intramuscular Quinine. PMID- 29009030 TI - Notes on Intravenous versus Intramuscular Quinine. PMID- 29009032 TI - An Unusual Case of Strangulated Hernia. PMID- 29009033 TI - A Clinical Study of Climatic Bubo and Allied Conditions. PMID- 29009034 TI - A Case of Cerebral Meningeal Haemorrhage. PMID- 29009035 TI - The Early Treatment of Malaria. PMID- 29009037 TI - Treatment of Soft Sore and Bubo. PMID- 29009036 TI - Some Observations after Splenectomy in Rabbits. PMID- 29009038 TI - Some Observations on the Combined Method of Clot Culture and Widal Reaction, and on the Prognostic Significance of 'Small-Flaking' or 'O'-Agglutinins in Typhoid Fever. PMID- 29009040 TI - Service Notes. PMID- 29009039 TI - Dysentery Produced by Bacterium Pseudocarolinus. PMID- 29009041 TI - Medical News. PMID- 29009042 TI - Volvulus in a Newborn Child. PMID- 29009043 TI - The Laboratory Diagnosis and the Treatment of Helminth Infections. PMID- 29009046 TI - A Case of Cerebro-Spinal Fever Successfully Treated by Intravenous Injections of Urotropine. PMID- 29009045 TI - Current Topics. PMID- 29009044 TI - A Study of Vitamin-A Deficiency in Ceylon with Special Reference to the Statistical Incidence of Phrynoderma and 'Sore Mouth'. PMID- 29009047 TI - Abstracts from Reports. PMID- 29009048 TI - The Pharmaceutical Profession and the 'Drugs Scandal'. PMID- 29009049 TI - A Case of Hydrophobia after Preventive Inoculation. PMID- 29009050 TI - Thyroid Extract in Prostatic Enlargement. PMID- 29009051 TI - A Case of Strangulated Hernia Relieved by Atropine. PMID- 29009052 TI - Removal of a Foreign Body from the OEsophagus. PMID- 29009053 TI - Acute Bacillary Dysentery in Children: Advantages of Its Treatment by Petroleum and Allied Preparations. PMID- 29009054 TI - Anti-Toxic Immunity to Diphtheria among a Group of Indians in Nainital District, U. P., India, as Evidenced by the Schick Tests. PMID- 29009055 TI - Cilia in the Anterior Chamber and Traumatic Cyst in the Iris. PMID- 29009056 TI - Toxic Effects of Emetine on the Cardiovascular System. PMID- 29009057 TI - Post-Puerperal Polyneuritis. PMID- 29009058 TI - Hernias of the Large Intestine, with Special Reference to Sliding Hernias. PMID- 29009059 TI - Voelcker's Method of Extraperitonealization of the Urinary Bladder: Its Usefulness in Operations for Pathological Conditions of the Bladder and the Ureters. PMID- 29009061 TI - Medical News. PMID- 29009060 TI - Fevers in Pregnancy. PMID- 29009062 TI - Nine Cases of Human Gnathostomiasis. PMID- 29009063 TI - Megacolon and Its Treatment by Sympathectomy. PMID- 29009064 TI - Calcareous Degeneration in a Uterine Fibroma. PMID- 29009065 TI - Studies on the Action of Quinine in Monkey Malaria. PMID- 29009066 TI - Notes and Observations on 'Infantile Biliary Cirrhosis'. PMID- 29009067 TI - Abstracts from Reports. PMID- 29009068 TI - Toxic Effects Produced by Combined Treatment with Atebrin and Plasmochin. PMID- 29009070 TI - Service Notes. PMID- 29009069 TI - Acute Perforation and Haematemesis in Duodenal Ulcer. PMID- 29009072 TI - Bored-Hole Latrines in the Health Unit, Partabgarh. PMID- 29009071 TI - A Cerebral Type of Malaria Lighted up by a Sudden Shock. PMID- 29009073 TI - The Total Cinchona Alkaloids. PMID- 29009074 TI - The Place of Treatment in an Antimalarial Campaign. PMID- 29009075 TI - Planocaine in Spinal Analgesia. PMID- 29009076 TI - Current Topics. PMID- 29009077 TI - Medical News. PMID- 29009078 TI - Malaria Control in Bengal. PMID- 29009079 TI - Normal Saline in Cholera. PMID- 29009080 TI - Clinical Observations on 636 Cases of Cerebro-Spinal Fever Treated in the Campbell Hospital, Calcutta, from March 1933 to March 1934. PMID- 29009082 TI - Current Topics. PMID- 29009081 TI - Carcinoma of the Stomach. PMID- 29009083 TI - A Case of Deformity of the Bones of the Hand and Feet of a Mother Transmitted to Her Child. PMID- 29009084 TI - Molluscum Contagiosum: A Preliminary Note on the Treatment. PMID- 29009085 TI - Ethidol in the Treatment of Tuberculous Adenitis. PMID- 29009086 TI - Multiple Ureteral Stones in a Ureterocele and Ureter. PMID- 29009088 TI - Abstracts from Reports. PMID- 29009087 TI - Medical College Centenary Celebrations Appeal. PMID- 29009089 TI - Basal Metabolism of Indians in Health and Disease-Its Clinical Significance. PMID- 29009090 TI - A Simple Method of Recovering Typical Cultures of Dermatophytes from Pleomorphic Growths. PMID- 29009091 TI - Service Notes. PMID- 29009092 TI - Treatment of Tuberculous Caries of the Spine. PMID- 29009093 TI - Further Observations on the Treatment of Oriental Sore. PMID- 29009095 TI - Two Cases of Bilateral Cervical Ribs. PMID- 29009094 TI - Some Impressions Derived from Experience in Cataract Extraction. PMID- 29009096 TI - Treatment of Opium Poisoning. PMID- 29009097 TI - Service Notes. PMID- 29009098 TI - Granuloma Venereum. PMID- 29009100 TI - Abstracts from Reports. PMID- 29009099 TI - General Paralysis of the Insane in Burma. PMID- 29009101 TI - Observations on the Thickness of the Frontal and Parietal Bones. PMID- 29009102 TI - A Study of Trachoma in Baluchistan. PMID- 29009103 TI - The Part Played by the Feeling of Guilt in the AEtiology of Mental Disorders. PMID- 29009104 TI - Hookworm Infection in the Punjab : Survey of a Rural Area in Ambala District. PMID- 29009105 TI - Treatment of Soft Sore and Bubo. PMID- 29009107 TI - The Chronic Primary Glaucomas. PMID- 29009106 TI - Treatment of Enlarged Spleens with Injections of Milk. PMID- 29009108 TI - Calcutta Medical College Centenary. PMID- 29009110 TI - Current Topics. PMID- 29009109 TI - Evipan Sodium for Small Operations. PMID- 29009111 TI - Medical News. PMID- 29009112 TI - Development of Health Education Work in the United Provinces. PMID- 29009113 TI - An Encouraging Result Obtained by the Use of E. C. C. O. in the Early Stage of Leprosy- Anaesthetic Type. PMID- 29009114 TI - The Indian Research Fund Association. PMID- 29009115 TI - Sodium Evipan Anaesthesia-A Study of 30 Cases. PMID- 29009116 TI - Service Notes. PMID- 29009117 TI - Abstracts from Reports. PMID- 29009118 TI - Conjunctivitis Produced by a Ground Beetle. PMID- 29009119 TI - Phrynoderma: A Condition Due to Vitamin Deficiency. PMID- 29009120 TI - A Case of Addison's Disease? PMID- 29009121 TI - Tetanus Cured by Magnesium Sulphate. PMID- 29009123 TI - A Case of Bilateral Macular Disease in a Child. PMID- 29009122 TI - Treatment of Typhoid Fever in Children. PMID- 29009124 TI - The AEtiology and Treatment of Retinal Detachment. PMID- 29009126 TI - Current Topics. PMID- 29009125 TI - Nephrolithiasis of the Horse-Shoe Kidney. PMID- 29009127 TI - Fracture Equipment: With Notes on Its Use. PMID- 29009128 TI - Fifty Years Ago. PMID- 29009129 TI - Intravenous Glucose in Pneumonia and Other Toxaemic Conditions like Eclampsia and Sutika. PMID- 29009131 TI - Medical News. PMID- 29009130 TI - Studies in Untreated Malaria. PMID- 29009132 TI - A Case of Gangrene Complicating Typhoid Fever. PMID- 29009134 TI - Primary Carcinoma of the Gall-Bladder. PMID- 29009133 TI - Post-Puerperal Polyneuritis. PMID- 29009136 TI - Current Topics. PMID- 29009135 TI - Therapeutic Property of Coconut Oil. PMID- 29009137 TI - Factors Influencing the Spread of Leprous Infection. PMID- 29009138 TI - A Case of Schizophrenia with Superimposed Benign Tertian Malaria Cured with Atebrin. PMID- 29009140 TI - Three Cases of Subcutaneous Intra-Abdominal Injury with Some Points in Diagnosis. PMID- 29009139 TI - Peri-Anal Ulceration Complicating Kala-Azar. PMID- 29009141 TI - Medical News. PMID- 29009143 TI - Abstracts from Reports. PMID- 29009142 TI - The Mica Myth in Darjeeling Water. PMID- 29009144 TI - Correspondence. PMID- 29009145 TI - Skeletal Traction by Means of Kirschner's Wire in the Treatment of Lower Limb Fractures. PMID- 29009146 TI - A Comparative Record of Anthelmintic Treatment with Tetrachlorethylene and Oil of Chenopodium. PMID- 29009147 TI - Service Notes. PMID- 29009149 TI - Treatment of Compound Fractures of Bones of the Leg by Skeletal Traction. PMID- 29009148 TI - Administration of Opium to Infants in India. PMID- 29009151 TI - Dietetics. PMID- 29009150 TI - A Case of Sarcoma of the Upper Jaw with Sinusitis of the Antrum of Highmore. PMID- 29009152 TI - Dental Myiasis. PMID- 29009154 TI - A Case of Psoriasis of Endocrine Origin. PMID- 29009153 TI - Atropine in Strangulated Hernia. PMID- 29009155 TI - Treatment of Soft Sore. PMID- 29009157 TI - Service Notes. PMID- 29009156 TI - A Large Urethral Calculus. PMID- 29009158 TI - Abstracts from Reports. PMID- 29009159 TI - Atebrin in Heavy Infection with P. Falciparum. PMID- 29009160 TI - Granuloma Venereum. PMID- 29009162 TI - Current Topics. PMID- 29009161 TI - Acriflavin in Cerebro-Spinal Meningitis. PMID- 29009163 TI - A Case of Cholera Sicca. PMID- 29009165 TI - The Value of Sanocrysin Treatment in Pulmonary Tuberculosis. PMID- 29009164 TI - Isospora Infection in Indian Cats. PMID- 29009166 TI - Carbarsone in Intestinal Amoebiasis. Part II. PMID- 29009167 TI - Medical News. PMID- 29009168 TI - Granuloma Genito-Inguinale. PMID- 29009169 TI - Oleothorax. PMID- 29009170 TI - Some Observations on Balantidium Coli and Entamoeba Histolytica of Macaques. PMID- 29009171 TI - A Note on the Treatment of Infective Granuloma with 'Fouadin'. PMID- 29009172 TI - A Calculus in the Tonsil. PMID- 29009174 TI - Waste, Wealth, and Health. PMID- 29009173 TI - An Unusual Form of Tuberculosis: Report of a Case. PMID- 29009175 TI - Abstracts from Reports. PMID- 29009176 TI - Syphilitic Cirrhosis of the Liver with Ascites in a Child: Report of a Case. PMID- 29009177 TI - The Incidence of Portal Cirrhosis of the Liver in Vizagapatam, Based on a Critical Study of Autopsy Records and Observations. PMID- 29009178 TI - Syphilitic Cirrhosis of the Liver Associated with Glycosuria in a Child: Report of a Case. PMID- 29009179 TI - Abdominal Pregnancy Secondary to Tubal Gestation at Term. PMID- 29009180 TI - Date Stone Causing Appendicitis. PMID- 29009181 TI - Notes on the Treatment of Oriental Sore with Berberine Acid Sulphate. PMID- 29009182 TI - Mental Suggestion in Everyday Life. PMID- 29009184 TI - Tebetren. PMID- 29009183 TI - Infantilism and Cirrhosis of the Liver. PMID- 29009185 TI - Constants of Cow Milk. PMID- 29009187 TI - Service Notes. PMID- 29009186 TI - Planocaine in Spinal Analgesia. PMID- 29009188 TI - An Ovarian Dermoid with Twisted Pedicle. PMID- 29009189 TI - Medical News. PMID- 29009190 TI - A New Intravenous Anaesthetic: Evipan Sodium. PMID- 29009191 TI - A Case of Resistant Protozoal Dysentery. PMID- 29009193 TI - A New Operation for the Cure of Ascites. PMID- 29009192 TI - The Sanitary Disposal and Agricultural Utilization of Habitation Wastes by the Indore Process. PMID- 29009195 TI - The AEtiology and Treatment of Retinal Detachment: January Number, pp. 4-7. PMID- 29009194 TI - Unsuspected Cholecystitis. PMID- 29009196 TI - Early Signs of Arsenical Poisoning. PMID- 29009197 TI - A Large Fibro-Lipoma. PMID- 29009198 TI - A Case of Hydrophobia after Preventive Inoculation. PMID- 29009199 TI - Radical Cure for Inguinal Hernia under Local Anaesthesia. PMID- 29009201 TI - Current Topics. PMID- 29009200 TI - A Case of Horny Papilloma. PMID- 29009202 TI - The Therapeutics of Malaria. PMID- 29009203 TI - Organic Manure from Street Refuse and Night-Soil at Mysore City, India. PMID- 29009205 TI - Maternity- And Child-Welfare Training. PMID- 29009204 TI - Further Observations on the Metabolism of Carotene. PMID- 29009206 TI - The Significance of the Thyro-Thymic Lymph System. PMID- 29009207 TI - The Incidence of Clonorchis Infection in India. PMID- 29009209 TI - Nutritive Value of Mustard Oil. PMID- 29009208 TI - The Toxic Effects of Emetine. PMID- 29009211 TI - Current Topics. PMID- 29009210 TI - Relapsing Malaria. PMID- 29009213 TI - The New British Pharmacopoeia and Indian Usage. PMID- 29009212 TI - A Case of Prolapsed Uterus. PMID- 29009214 TI - Planocaine in Spinal Anaesthesia. PMID- 29009215 TI - A New Capsule Forceps. PMID- 29009216 TI - Congenital Syphilis. PMID- 29009217 TI - Service Notes. PMID- 29009218 TI - Medical News. PMID- 29009219 TI - Naga Sore in a Tea-Estate Practice. PMID- 29009220 TI - Results of Gold Therapy. PMID- 29009221 TI - A Case of Weil's Disease or Infective Jaundice. PMID- 29009223 TI - Tropical Phagedaenic Ulcer (Naga Sore). PMID- 29009222 TI - Prevention of Cholera in Rural India. PMID- 29009224 TI - A Method of Plating Stools. PMID- 29009225 TI - Abstracts from Reports. PMID- 29009226 TI - Diagnosis and Treatment of Some Urinary Complications in Gynaecology. PMID- 29009227 TI - Tinea Imbricata (Tokelau) in Bengal. PMID- 29009228 TI - Malarcan in the Treatment of Indian Strains of Malaria. PMID- 29009229 TI - Acute Psoas Abscess. PMID- 29009230 TI - Surgery of the Sympathetic. PMID- 29009231 TI - Diagnostic Significances of Urobilinuria in Cases of Pyrexia. PMID- 29009233 TI - Current Topics. PMID- 29009232 TI - Study of Vitamin-A Deficiency in Ceylon. PMID- 29009235 TI - Anti-Malarial Work on a Group of Tea Estates in South Sylhet. PMID- 29009234 TI - A Case of Resuscitation by Puncture of the Ventricle. PMID- 29009236 TI - A Form of Generalized OEdema Attended with Malnutrition Which Is Becoming Increasingly Common in Rangoon. PMID- 29009237 TI - Hot Weather Ear-A Clinical Entity. PMID- 29009239 TI - A Case of Pseudocyesis Followed by True Pregnancy. PMID- 29009238 TI - 'Backdoor Drainage', an Anti-Malarial Measure Designed to Meet a Particular Physiographical Situation in Sylhet District, Assam. PMID- 29009240 TI - Study of Vitamin-A Deficiency in Ceylon. PMID- 29009242 TI - Abstracts from Reports. PMID- 29009241 TI - Rupture of the Heart: With Slight External Marks of Violence. PMID- 29009243 TI - Medical News. PMID- 29009244 TI - A Case of Extravasation of Urine Due to a Calculus in a Child Six Years of Age. PMID- 29009245 TI - A Case of Cardiac Failure with Complete Heart Block. PMID- 29009246 TI - Glabellar Presentation, Its Incidence and Termination. PMID- 29009247 TI - A Treatment of Acute Intestinal Obstruction. PMID- 29009248 TI - Medical Research. PMID- 29009250 TI - Service Notes. PMID- 29009249 TI - A Case of Empyema Necessitatis, Cured by Aspiration Alone. PMID- 29009251 TI - A Case of Hydatid Cyst of the Lung. PMID- 29009252 TI - The Treatment of Acne. PMID- 29009253 TI - Spinal Percain Anaesthesia. PMID- 29009255 TI - Service Notes. PMID- 29009254 TI - Ammonium Chloride in the Treatment of Nephritic OEdema. PMID- 29009257 TI - Medical News. PMID- 29009256 TI - 'Novostiburea' in the Treatment of Kala-Azar. PMID- 29009258 TI - An Account of the Epidemic of Cerebro-Spinal Fever in the Borstal Institution. PMID- 29009259 TI - Prolapse of Lung Following an Injury. PMID- 29009261 TI - Air Traffic and Yellow Fever. PMID- 29009260 TI - Some Bypaths of Orthopaedic Surgery. PMID- 29009262 TI - Observations on an Epidemic of Whooping-Cough at the Lawrence Royal Military School, Sanawar: With a Note on the Investigation of a Skin Reaction in This Disease. PMID- 29009263 TI - Indian Male Nurses. PMID- 29009264 TI - Notes on Berberine Sulphate in Oriental Sore. PMID- 29009265 TI - Comparative Notes on the Cryoscopy of Milk. PMID- 29009266 TI - A Case of Impacted Vesical Calculus. PMID- 29009268 TI - Current Topics. PMID- 29009267 TI - The Arneth Count, with Particular Reference to Its Diagnostic Value in Asthma. PMID- 29009269 TI - Creeping Eruption Produced by Hookworm Larvae. PMID- 29009271 TI - Medical News. PMID- 29009270 TI - A Case of Spontaneous Pneumothorax. PMID- 29009272 TI - Intensive Iron Treatment of Anaemia in a Tea-Garden Labour Force. PMID- 29009273 TI - Syphilis of the Brain. PMID- 29009274 TI - A Note on the Use of Marmite in Tropical Macrocytic Anaemia, Including Pernicious Anaemia of Pregnancy. PMID- 29009275 TI - The Occurrence of Haemoglobinuria during Treatment of Malarial Fever with Atebrin and Plasmoquine. PMID- 29009277 TI - Fatal Flexner Bacillus Infection in an Anthropoid Ape (Hylobates Hoolock). PMID- 29009276 TI - Urobilinuria and Its Importance in Malaria. PMID- 29009278 TI - The Role of Chaetopods (Segmented Worms) in Their Relation to Man. PMID- 29009279 TI - Jaundice and Acute Mania Following Combined Carbon Tetrachloride and Oil of Chenopodium Treatment for Hookworm. PMID- 29009280 TI - Notes on Making Epidemic Forecasts. PMID- 29009281 TI - A Case of Acute Lupus Erythematosus Disseminatus. PMID- 29009283 TI - Service Notes. PMID- 29009282 TI - Strangulated Hernia Reduced by Atropin and Adrenalin Injections. PMID- 29009284 TI - Sixth British Pharmacopoeia (1932). PMID- 29009286 TI - A Note on the Prevalence of Lead Poisoning in India. PMID- 29009285 TI - Malignant Disease in the Punjab. PMID- 29009287 TI - Report on a Case of Tubercular Iritis. PMID- 29009288 TI - Life Tables for Bengal, with Notes on the Method of Preparation of Life Tables. PMID- 29009289 TI - Current Topics. PMID- 29009290 TI - Tropical Gynaecology and Obstetrics: A Post-Graduate Clinical Lecture. PMID- 29009291 TI - Hydrochloric Acid Intravenously in the Treatment of Puerperal Infection. PMID- 29009292 TI - Yaws in the Nicobar Islands. PMID- 29009293 TI - A New Corneal Scraper for Tattooing. PMID- 29009295 TI - Medical News. PMID- 29009294 TI - Pantocain-A New Cocaine Substitute. PMID- 29009296 TI - Studies on Inguinal Granuloma: Part I The Lesion and Mode of Infection. PMID- 29009297 TI - Acute Painful Conditions of the Ear. PMID- 29009298 TI - A Case of Elephantoid Penis. PMID- 29009299 TI - The Treatment of Chronic Intestinal Amoebiasis with the Alkaloids of Holarrhena Antidysenterica (Kurchi). PMID- 29009300 TI - Three Fatal Cases of Blackwater Fever. PMID- 29009301 TI - Comparative Notes on the Cryoscopy of Milk. PMID- 29009302 TI - Two Cases of Pityriasis Rubra Pilaris. PMID- 29009303 TI - Cyanosis after Plasmochin. PMID- 29009305 TI - Recent Researches on Blackwater Fever. PMID- 29009304 TI - Rabies in the Mongoose: Further Observations. PMID- 29009306 TI - Result of the Forecast of Cholera, Smallpox and Plague in India in 1932 and Forecast for 1933. PMID- 29009307 TI - Milk Injections in Splenic Enlargements Due to Malaria. PMID- 29009308 TI - Foreign Body in the Rectum. PMID- 29009309 TI - A Study on the Preparation of an Efficient Extract of Kurchi (Holarrhena Antidysenterica). PMID- 29009310 TI - Splenectomy. Indications and Results, with Special Reference to Conditions Obtaining in the Tropics. PMID- 29009311 TI - Sex Hormones of Females. PMID- 29009313 TI - Current Topics. PMID- 29009312 TI - The Duration of the Life of the Embryos of Wuchereria Bancrofti in the Human System. PMID- 29009314 TI - The Medical Profession and the Birth Control Movement. PMID- 29009315 TI - Calculus Impacted in the Urethra. PMID- 29009316 TI - Service Notes. PMID- 29009317 TI - An Easy Method for Estimating the Protein Content of Milk. PMID- 29009318 TI - Ceylon Health Units. PMID- 29009319 TI - The Pathology of Elephantiasis of Filarial Origin. PMID- 29009320 TI - Association of Medical Women in India. PMID- 29009321 TI - Current Topics. PMID- 29009322 TI - A Leech in the Nasal Cavity and Its Removal. PMID- 29009323 TI - A Penetrating Wound of the Abdomen. PMID- 29009325 TI - Antiphlogistine Substitutes. PMID- 29009324 TI - The Present Methods of the King Institute in the Production of Vaccine Lymph. PMID- 29009326 TI - A Case of Diaphysial Aclasis. PMID- 29009327 TI - Anti-Rabic Treatment. PMID- 29009329 TI - Service Notes. PMID- 29009328 TI - Treatment of Chronic Intestinal Amoebiasis with Carbarsone. PMID- 29009330 TI - The Occurrence of Haemoglobinuria during Treatment of Malarial Fever with Atebrin and Plasmoquine. PMID- 29009331 TI - Rice Infection and Epidemic Dropsy. PMID- 29009332 TI - The Non-Toxicity of Plasmochin and Atebrin. PMID- 29009333 TI - Vaccination against Smallpox. PMID- 29009334 TI - Acute Massive Atelectatic Collapse of the Lungs. PMID- 29009335 TI - The Synthetic Anti-Malarial Compounds. PMID- 29009337 TI - Medical News. PMID- 29009336 TI - Lethal Properties of Aqueous Extract of Young Bamboo Shoots. PMID- 29009338 TI - A Fatal Case of Ambulant Typhoid Fever. PMID- 29009339 TI - The Choice of a General Anaesthetic in Major Operations in India. PMID- 29009340 TI - Service Notes. PMID- 29009341 TI - Removal of a Foreign Body from the OEsophagus. PMID- 29009342 TI - The Anaemia of the Leishmania-Infected Hamster. PMID- 29009343 TI - A Note on the Value of the Ascitic Fluid for the Wassermann Reaction and Agglutination Tests with Dysentery Organisms. PMID- 29009345 TI - Medical News. PMID- 29009344 TI - A Cause of Damage to Optical Glass in the Tropics. PMID- 29009346 TI - Some Country Beers of India. PMID- 29009347 TI - Spinal Analgesia. PMID- 29009348 TI - Ethyl Chloride for Short Anaesthesia. PMID- 29009349 TI - Passage of a Safety-Pin through the Alimentary Canal. PMID- 29009350 TI - Dangers of Exhaust Fumes. PMID- 29009351 TI - Basal Anaesthesia. PMID- 29009352 TI - An Interesting Case of Compound Depressed Fracture of the Skull. PMID- 29009354 TI - Anaesthetics in India. PMID- 29009353 TI - Pseudarthrosis of Humerus. PMID- 29009355 TI - Current Topics. PMID- 29009356 TI - Phrynoderma : A Condition Due to Vitamin Deficiency. PMID- 29009357 TI - Modern Methods of Anaesthesia from the Surgeon's Standpoint. PMID- 29009358 TI - Complete Transposition of the Viscera. PMID- 29009359 TI - Suppressed Menstruation. PMID- 29009360 TI - A Case of Cerebellar Tumour. PMID- 29009361 TI - Volvulus of the Sigmoid. PMID- 29009362 TI - On the Therapeutic Value of Thiosarmine in the Treatment of Syphilis. PMID- 29009364 TI - The Antigenic Power of Antidysenteric Bilivaccine, as Demonstrated by a Serological Method. PMID- 29009363 TI - On the Therapeutic Value of Thio-Sarmine in the Treatment of Syphilis. PMID- 29009365 TI - Diet as a Possible Factor in the Causation of Stone in the Bladder in the Punjab. PMID- 29009366 TI - Encephalitis Lethargica in Assam. PMID- 29009367 TI - Cytological Studies of the Blood and Tissues in Kala-Azar and Associated Conditions: Part IV. The Large Mononuclear Cells in Monkey Malaria. PMID- 29009368 TI - Berberine Sulphate in Chronic Trachoma. PMID- 29009369 TI - Neuro-Toxins and Bamboo Shoots. PMID- 29009370 TI - A Case of 'Abnormal Blood Group' in Which Transfusion Was Performed. PMID- 29009371 TI - A Case of Lymphocytic Leukaemia. PMID- 29009372 TI - Cytological Studies of the Blood and Tissues in Kala-Azar and Associated Conditions: Part V. The Large Mononuclear Cells in the Peripheral and in the Spleen Blood in Kala-Azar. PMID- 29009373 TI - Medical News. PMID- 29009374 TI - Current Topics. PMID- 29009375 TI - A Small Epidemic of Flexner (?) Dysentery. PMID- 29009376 TI - Leech Bite of Labium Majus. PMID- 29009377 TI - The Effect of Locality on Filarial Manifestations. PMID- 29009378 TI - Service Notes. PMID- 29009379 TI - An Arrow Wound of the Abdomen. PMID- 29009380 TI - Leprosy Relief in India: A Review of the Present Situation, and a Suggested Policy for Provincial and Local Authorities. PMID- 29009381 TI - Immunity in Protozoal Infections. PMID- 29009382 TI - The New Year's Honours. PMID- 29009383 TI - A Note from an Estate Medical Practice in Malaya. PMID- 29009384 TI - A Case of Purpura Haemorrhagica. PMID- 29009385 TI - Studies on Inguinal Granuloma : II. The Bacterial Flora of Granuloma. PMID- 29009386 TI - Bacillaemia in Leprosy. PMID- 29009387 TI - Studies on the Action of Atebrin in Plasmodium Infection of Monkeys. PMID- 29009389 TI - Insanity Treated by Sulphur Injection. PMID- 29009388 TI - Recurrent Volvulus of the Sigmoid Colon Cured by Complete Sigmoidectomy. PMID- 29009390 TI - A Calculus in the Tonsil. PMID- 29009392 TI - Current Topics. PMID- 29009391 TI - Studies on Inguinal Granuloma: III. The Donovan Organism of Granuloma. PMID- 29009393 TI - The Mechanism of Immunity in Malaria: Proof of the Phagocytosis of Malarial Parasites by Large Mononuclear Cells in Malaria. PMID- 29009394 TI - Vaccination against Smallpox. PMID- 29009395 TI - A Case of Hiccough Cured with Apomorphine Hydrochloride. PMID- 29009396 TI - Congenital Dilatation of the Foetal Urinary Bladder. PMID- 29009398 TI - Service Notes. PMID- 29009397 TI - A New Operation for Drainage of the Pleura. PMID- 29009399 TI - Medical News. PMID- 29009400 TI - Some Notes on Planocain in Spinal Analgesia. PMID- 29009401 TI - Some Observations on Two Cases of Disorder of the Liver in Infancy and Childhood. PMID- 29009402 TI - A Case of Endocarditis Treated with Polyvalent Antistreptococcus Serum. PMID- 29009403 TI - Observations on an Unusual Case of Acute Haemorrhagic Purpura. PMID- 29009404 TI - Modi's Medical Jurisprudence. PMID- 29009405 TI - A Penetrating Wound of the Anus. PMID- 29009407 TI - Cholera and Bengal. PMID- 29009406 TI - On Ectopic Gestation. PMID- 29009409 TI - Current Topics. PMID- 29009408 TI - Persistent Left Superior Vena Cava. PMID- 29009410 TI - Servants of India Society Flood Relief Fund. PMID- 29009411 TI - Animal Paratyphoid in Guinea-Pigs. PMID- 29009412 TI - Spasmodic Stricture of the Gullet. PMID- 29009413 TI - Intestinal Obstruction Relieved by Atropine. PMID- 29009414 TI - An Unusual Strangulated Hernia. PMID- 29009415 TI - The Diagnosis of the Clinical Types of Asthma and Their Causation. PMID- 29009416 TI - Cardiovascular and Other Manifestations of Epidemic Dropsy. PMID- 29009417 TI - Spread of Cutaneous Leishmaniasis along Lymphatics. PMID- 29009418 TI - Spina Bifida with Meningomyelocele. PMID- 29009419 TI - The Formula of Atebrin. PMID- 29009420 TI - Erratum: The Anaemia of Kala-Azar. AB - [This corrects the article on p. 545 in vol. 68.]. PMID- 29009422 TI - Service Notes. PMID- 29009421 TI - Carbon Tetrachlorethylene in the Treatment of Hookworm Infection. PMID- 29009423 TI - Medical News. PMID- 29009424 TI - A Case of Dysidrosis Treated by Calcium. PMID- 29009425 TI - Bronchoscopy in Asthma and Other Cases. PMID- 29009426 TI - Fevers in Pregnancy. PMID- 29009427 TI - Eight Cases of Plague Treated with 'Bayer 205'. PMID- 29009428 TI - Toxic Effects of Ephedrine-A Warning. PMID- 29009430 TI - Beri-Beri and Epidemic Dropsy. PMID- 29009429 TI - Congenital Absence of the Eyes. PMID- 29009431 TI - A Large Pedunculated Lipoma on the Neck. PMID- 29009432 TI - The Dosage of Plasmochin. PMID- 29009433 TI - A Case of Tabes Dorsalis in an Indian. PMID- 29009434 TI - A Serological Proof of Ethnological Identity of the Hindus and the Mohammedans of Assam. PMID- 29009435 TI - The Frequency of Hydatid Disease in India. PMID- 29009436 TI - Further Notes on Pellagra in Hyderabad Deccan. PMID- 29009437 TI - Medical News. PMID- 29009438 TI - A Plea for Collapse Therapy in the Early Stages of Pulmonary Tuberculosis. PMID- 29009439 TI - Pellagra in Guntur. PMID- 29009440 TI - Morphine Habit in India. PMID- 29009441 TI - Filarial Worms under the Human Conjunctiva. PMID- 29009443 TI - Mixed Tumour of the Face, Not Associated with the Parotid Gland. PMID- 29009442 TI - Pantocaine in Eye-Surgery. PMID- 29009444 TI - Service Notes. PMID- 29009445 TI - Syphilitic Iritis Treated by an Unqualified Practitioner. PMID- 29009446 TI - A Case of Dermographia with a Short Note on the AEtiology of the Condition. PMID- 29009447 TI - A Case of Cutaneous Plague. PMID- 29009448 TI - A Few Observations on the Pharmacology and Therapeutics of Muscle Extract. PMID- 29009449 TI - Training for Maternity and Infant Welfare Work. PMID- 29009450 TI - Some Factors Regulating Metastasis in Carcinoma and Their Influence on Prognosis. PMID- 29009451 TI - Annual Report of the European and Indian Mental Hospitals, Ranchi, for 1931. PMID- 29009452 TI - On the Incidence of Arsenical Dermatitis. PMID- 29009453 TI - Current Topics. PMID- 29009455 TI - The Treatment of Acne. PMID- 29009454 TI - A Case of Fibro-Lipomatosis Associated with Fever. PMID- 29009457 TI - Service Notes. PMID- 29009456 TI - 'Vincent's Disease' in a Macaca Irus Monkey. PMID- 29009458 TI - Cancrum Oris in a Monkey Infected with Leishmania Donovani. PMID- 29009459 TI - Current Topics. PMID- 29009461 TI - An Iron Ring on the Penis. PMID- 29009460 TI - A Schematic Representation of the Variants of Cholera Vibrio Produced under the Influence of Bacteriophage. PMID- 29009462 TI - The Constancy of the Sugar-Chloride Relationship in Diabetic Urines. PMID- 29009463 TI - Atebrin in the Treatment of Indian Strains of Malaria. PMID- 29009464 TI - The Filtrable Phase of the Tubercle Bacillus: Preliminary Note. PMID- 29009465 TI - Experimental Studies with a Spirillum Found in the Nasal Cavity of Some Lepers. PMID- 29009466 TI - Double Papilloedema Following Antirabic Inoculation: Recovery. PMID- 29009467 TI - The Role of the Eosinophiles in the Diagnosis of Spasmodic Asthma. PMID- 29009468 TI - Medical News. PMID- 29009469 TI - Diabetes in Children. PMID- 29009470 TI - A Pedunculate Lipoma. PMID- 29009471 TI - The International Population Union. PMID- 29009472 TI - A Note on Professor Nicolle's Views on the Typhus and Relapsing Fevers. PMID- 29009473 TI - A Case of Tropical Typhus Serologically Related to 'Scrub Typhus' of the Federated Malay States. PMID- 29009474 TI - The Census and the Medical Profession in Bengal. PMID- 29009475 TI - Chorio-Epithelioma or Deciduoma Malignum. PMID- 29009476 TI - Current Topics. PMID- 29009477 TI - Medical News. PMID- 29009478 TI - Acute Inversion of the Uterus. PMID- 29009479 TI - An Analysis of One Hundred and Fifty Cases of Asthma. PMID- 29009480 TI - Vaccination against Smallpox. PMID- 29009481 TI - A Case of Typhoid Fever with Cerebral Symptoms. PMID- 29009483 TI - A Case of Rabies with an Unusually Long Incubation Period. PMID- 29009482 TI - The Zondek-Aschheim Test for Pregnancy as Studied in 200 Cases. PMID- 29009484 TI - The Classification of the Anaemias. PMID- 29009485 TI - A Leech in the Nasal Cavity and Its Removal. PMID- 29009486 TI - Notes on Indian Plague Rats. PMID- 29009487 TI - A Rare Type of Dermal Leishmaniasis. PMID- 29009489 TI - Certain Injuries of the Wrist That Are Frequently Overlooked. PMID- 29009488 TI - Hydatid Disease in South India. PMID- 29009490 TI - Service Notes. PMID- 29009491 TI - A Case of Neurasthenia Apparently Cured by a Diet of Ghee. PMID- 29009492 TI - Brief Note on the Results Obtained with Anti-Gametocyte Treatment Only, without Anti-Larval Measures. PMID- 29009493 TI - Gram-Negative-Bacilli Isolated from the Sputum in Cases of Asthma. PMID- 29009494 TI - The Action of Some Synthetic Antimalarial Remedies on the Uterus. PMID- 29009495 TI - Ability to Walk a Long Distance and Give Dying Declaration after Severe Head Injury. PMID- 29009496 TI - A Colorimetric Method for the Determination of Milk Proteins. PMID- 29009497 TI - The Anaemia of Kala-Azar. PMID- 29009498 TI - Biliary Lithiasis: Part I. PMID- 29009499 TI - Medical News. PMID- 29009500 TI - A Case of Purpura Rheumatica (Schonlein's Disease). PMID- 29009501 TI - The Early Signs of Mental Disorders. PMID- 29009503 TI - Passage of a Needle through the Alimentary Canal. PMID- 29009502 TI - The Toxicity of Tetrachlorethylene to Cats. PMID- 29009504 TI - A Vesical Calculus of Unusual Size. PMID- 29009506 TI - Service Notes. PMID- 29009505 TI - Gonorrhoea in a Boy of Seven. PMID- 29009507 TI - The Problem of Leprosy. PMID- 29009508 TI - A Large Fibro-Adenoma of Neck. PMID- 29009509 TI - Erratum: Fungous Diseases: A Clinico-Mycological Text. AB - [This corrects the article on p. 353d in vol. 68.]. PMID- 29009510 TI - A Case with Absence of Polymorphonuclear Leucocytes. PMID- 29009511 TI - Splenectomy for Splenic Cyst. PMID- 29009512 TI - A Leech in the Male Urethra. PMID- 29009514 TI - Faecal Bacteria in Bengal as Indicators of Sewage Contamination of Water : A Preliminary Study. PMID- 29009513 TI - Chronic Amoebic Infection as a Cause of Ill-Health. PMID- 29009515 TI - Bronchoscopy : Its Usefulness in India. PMID- 29009516 TI - Current Topics. PMID- 29009517 TI - Service Notes. PMID- 29009518 TI - Congenital Deficiency of Two Fingers and Their Metacarpal Bones. PMID- 29009520 TI - The Position of the Indian Medical Councils to the General Medical Council of London and the Status of British English Medical Degrees and Diplomas. PMID- 29009519 TI - Berberine Sulphate in Oriental Sore. PMID- 29009521 TI - The Fate of the Merozoites Seen in the Cultures of Malarial Parasites. PMID- 29009522 TI - The Illness of H. M. the King-Emperor. PMID- 29009523 TI - On the Determination of Age in Indians, from a Study of the Ossification of the Epiphyses of the Long Bones. PMID- 29009524 TI - A Heart Case-For Diagnosis. PMID- 29009525 TI - A Case of Unusually Large Cystic Goitre. PMID- 29009526 TI - The Present Position of Medical Science in India. PMID- 29009527 TI - Studies in the Treatment of Filariasis. PMID- 29009528 TI - On the Anopheline Mosquitoes of Hazaribagh (Bihar and Orissa). PMID- 29009529 TI - Radiology in the Diagnosis of Chronic Appendicitis. PMID- 29009530 TI - A Case of Post-Kala-Azar Dermal Leishmaniasis. PMID- 29009532 TI - Notes on Current Topics. PMID- 29009531 TI - Gastric Syphilis. PMID- 29009533 TI - Blood Tests in Relation to Blood Transfusion. PMID- 29009535 TI - The Response of a Group of Indian Infants and Children to the Schick Test. A Preliminary Report of 186 Tests. PMID- 29009534 TI - A Case of Bleeding from the Breast. PMID- 29009536 TI - Treatment of Gonorrhoea. PMID- 29009537 TI - Auricular Fibrillation after Aspirin. PMID- 29009538 TI - Night Blindness and Its Speedy Cure with Liver. PMID- 29009539 TI - Estimation of Blood Sugar. PMID- 29009540 TI - A Case of Hysteria (Narcolepsy?). PMID- 29009541 TI - Some Sources of Vitamin C in India. PMID- 29009542 TI - Berberine in the Treatment of Oriental Sore. PMID- 29009543 TI - Alastrim or Small-Pox? PMID- 29009544 TI - Musculo-Spiral Nerve Paralysis Following an Intramuscular Injection of Quinine. PMID- 29009545 TI - A Case of Cephalic Tetanus. PMID- 29009546 TI - Notes on Current Topics. PMID- 29009547 TI - A Preliminary Note on the Action of Vasopressin and Oxytocin. PMID- 29009548 TI - Homogentisuria (Alkaptonuria) with Glycosuria. With Notes on a Detailed Clinical and Chemical Investigation of a Case. PMID- 29009549 TI - Service Notes. PMID- 29009550 TI - The History of Tick-Bites in Cases of Tick-Typhus in India. PMID- 29009551 TI - The Problem of Population. PMID- 29009552 TI - Terminalia Arjuna: Its Chemistry, Pharmacology and Therapeutic Action. PMID- 29009554 TI - A Case of Syphilitic Basal Meningitis. PMID- 29009553 TI - The Spread of Dysentery in a Khasi Village and Its Treatment with Bacteriophage. PMID- 29009555 TI - Corrigendum. AB - [This corrects the article on p. 50b in vol. 64.]. PMID- 29009556 TI - Intravenous Calcium Therapy. PMID- 29009557 TI - The Campaign against Leprosy. PMID- 29009558 TI - Hints on the Village Nurse Scheme. PMID- 29009560 TI - Two Cases of Surgical Interest. PMID- 29009559 TI - A Case for Diagnosis. PMID- 29009561 TI - Diphtheria in India. PMID- 29009563 TI - An Undescended Testicle in an Unusual Position. PMID- 29009562 TI - Occurrence of Chyluria after Confinement. PMID- 29009564 TI - A New Suggestion in Malaria Control. PMID- 29009565 TI - A Case of Irreducible Hernia Relieved by Atropine Sulphate. PMID- 29009566 TI - Two Cases of Leprosy Successfully Treated. PMID- 29009567 TI - A Case of Raynaud's Disease. PMID- 29009568 TI - The Sterilization of Hypodermic Syringes. PMID- 29009569 TI - Notes on the Use of Carbon Tetrachloride. PMID- 29009570 TI - Malaria Therapy in Tabes Dorsalis. PMID- 29009571 TI - A Case of Aphasia during Spinal Anaesthesia. PMID- 29009572 TI - Service Notes. PMID- 29009573 TI - A Further Note on the Treatment of Vesico-Vaginal Fistula by Rectal Transplantation of the Ureters. PMID- 29009574 TI - Wertheim Schanta's Interposition Operation for Complete Prolapse of the Uterus. PMID- 29009575 TI - The Successful Use of a Tuberculous Methylic Antigen in External Tuberculosis. PMID- 29009576 TI - The Treatment of Vaginismus. PMID- 29009577 TI - A Case of Enteric in Which the Widal Reaction Became Positive on the 49th Day. PMID- 29009578 TI - Notes on "The Significance of the Antimony Test in the Diagnosis of Kala-Azar". PMID- 29009579 TI - A Case for Diagnosis. PMID- 29009580 TI - A Note on Museum Making. PMID- 29009581 TI - A Note on the Action of Synthetic Adrenaline. PMID- 29009582 TI - A Case of Urticaria. PMID- 29009583 TI - The Indications for Suprapubic Cystotomy. PMID- 29009584 TI - New Conceptions of Sciatic Pain and Its Treatment. PMID- 29009585 TI - Naga Sores in Gwalior. PMID- 29009587 TI - Corrigenda. AB - [This corrects the article on p. 601 in vol. 64.]. PMID- 29009586 TI - The Significance of the Antimony Test in the Diagnosis of Kala-Azar: Part I-Serum Tests. PMID- 29009588 TI - An Inquiry into the Physical Conditions of Indian Labour: A Preliminary Communication. PMID- 29009589 TI - Bogus "M.Ds." PMID- 29009590 TI - A Simple Method of Standardizing the Red Cell Suspension in Connection with the Wassermann Reaction. PMID- 29009591 TI - Aluminium Utensils and Tuberculosis. PMID- 29009593 TI - Current Topics. PMID- 29009592 TI - Notes on Malaria in the Sibsagar District, Assam. PMID- 29009594 TI - Gonorrhoea and Its Treatment with "Acriflavin". PMID- 29009595 TI - T. A. B. Vaccine in Relation to an Outbreak of Enteric Fevers. PMID- 29009596 TI - Dysentery in the Central Jail, Rajamandry, Madras Presidency. PMID- 29009598 TI - Research in Filariasis. PMID- 29009597 TI - Tropical Dietaries. PMID- 29009599 TI - Plasmochin Compositum in the Treatment of Malaria. PMID- 29009600 TI - A Case of Intolerance to Quinine. PMID- 29009601 TI - "Kataphylaxia," a Phenomenon Seen Clinically in Filariasis. PMID- 29009602 TI - The Treatment of Myiasis in Lepers. PMID- 29009603 TI - Sterilization of Hypodermic Syringe. PMID- 29009604 TI - Notes on the Detection in the Urine of Some Drugs Used for the Treatment of Malaria. PMID- 29009605 TI - Intravenous Iodine in Ulcus Tropicum. PMID- 29009606 TI - The Age of Consent Act. PMID- 29009607 TI - A Case of Human Infection with a Gnathostome in India. PMID- 29009608 TI - Observations on a Series of Bacteriological Examinations of Tube Well Water in Rangoon. PMID- 29009609 TI - Epidemic Jaundice (Weil's Disease) or Malaria in Kandi Subdivision of Murshidabad District in 1928. PMID- 29009610 TI - Filarial Lymphangitis. PMID- 29009611 TI - The Indian Medical Department. PMID- 29009612 TI - The Infectiousness of Leprosy. PMID- 29009613 TI - A Record of Malarial Cases in the Bengal-Nagpur Railway Construction Hospital, Titlagarh, from July 1928 to August 1929, with Some Observations on Mosquito Findings and Conditions of Transmission. PMID- 29009614 TI - A Chronic Encysted Mammary Abscess Simulating Scirrhous Cancer. PMID- 29009615 TI - A Case of Filarial Abscess. PMID- 29009616 TI - Notes on Current Topics. PMID- 29009618 TI - Service Notes. PMID- 29009617 TI - The Value of Preventive Inoculation against Cholera: Some Figures from Burma. PMID- 29009619 TI - Medical News. PMID- 29009621 TI - Service Notes. PMID- 29009620 TI - Peritoneal Forceps. PMID- 29009622 TI - An Interesting Case of "Chorea". PMID- 29009623 TI - Causes of Blindness: A Statistical Report from the Swedish Mission Hospital, Tirupattur, Ramnad District, for a Period of Ten Months (from 1st January to 31st October, 1928). PMID- 29009624 TI - Indian Dietaries in the United Provinces. PMID- 29009626 TI - Notes on Current Topics. PMID- 29009627 TI - Ophthalmology in Relation to Research : Bring the Presidential Address to the Medical and Veterinary Research Section of the Sixteenth Indian Science Congress, Held at Madras in January, 1929. PMID- 29009625 TI - A Note on Spirillum Minus (Carter), the Causative Organism of Rat-Bite Fever. PMID- 29009628 TI - Apyrexial Pneumonia. PMID- 29009629 TI - A Note on the Anophelines Found in Baroda Camp. PMID- 29009630 TI - An Unusual Complication of Kala-Azar. PMID- 29009631 TI - A Vaccine for the Treatment of Phthisical Patients Who Expectorate Tubercle Bacilli in the Sputum. PMID- 29009632 TI - Medical News. PMID- 29009633 TI - A Case of a Rubber Catheter inside the Bladder. PMID- 29009634 TI - Notes on a Case of Bacillus Coli Septicaemia. PMID- 29009635 TI - On a Recent Outbreak of Epidemic Dropsy in the District of Birbhum. PMID- 29009636 TI - Chemotherapy. PMID- 29009638 TI - Notification of Dangerous Diseases. PMID- 29009637 TI - A Case of Inguinal Hernia with a Faecal Tumour in the Scrotum. PMID- 29009639 TI - An Improvised Drop Regulator. PMID- 29009640 TI - An Interesting Case of Recurrent Pregnancy Toxaemia. PMID- 29009641 TI - Epidemic Dropsy in Birbhum. PMID- 29009642 TI - A Modified Sippy's Line of Treatment in Duodenal Ulcer. PMID- 29009643 TI - Analysis of a Hundred Cases of Cataract Extraction at the Raipur Main Hospital by Smith's Method with a Flap of Conjunctiva. PMID- 29009644 TI - The Intravenous Use of Pituitrin. PMID- 29009645 TI - A Case of Ivory-Grafting. PMID- 29009646 TI - A Case of Exfoliative Dermatitis after Neosalvarsan Injections. PMID- 29009647 TI - The AEtiology of Naga Sore. PMID- 29009649 TI - Detachment of the Retina: A Complete Cure in a Myopic Case. PMID- 29009648 TI - Plasmoquin in Pregnancy. PMID- 29009650 TI - Breath Sucker Snakes. PMID- 29009652 TI - Tattooing of the Cornea with Platinum Chloride Solution for Leucoma. PMID- 29009651 TI - A Suggestion for Improvement in the Dietary of the Indian Community to Secure a Higher Degree of Health and Efficiency. PMID- 29009653 TI - An Interesting Early Right-Sided Goitre: With a Mild Paratyphosus a Complication. PMID- 29009654 TI - William Harvey's Message to India: Being an Address Delivered to University College Medical Society, Rangoon, 1928. PMID- 29009655 TI - The Treatment of Vesico-Vaginal Fistula by Rectal Transplantation of the Ureters. PMID- 29009656 TI - A Crochet Needle as an Emergency Surgical Instrument. PMID- 29009658 TI - A Case of Acute Ascending (Landry's?) Paralysis. PMID- 29009657 TI - A Case of Psuedo-Pregnancy. PMID- 29009659 TI - A Case of "Glandular Fever". PMID- 29009660 TI - Leprosy in Manipur State. PMID- 29009661 TI - The Treatment of Night Blindness. PMID- 29009662 TI - Malignant Anaemia of the Tropics. PMID- 29009663 TI - Observations on the Potency of Indian Digitalis. PMID- 29009664 TI - Erratum: The Indian Medical Year, 1928: Corrigendum. AB - [This corrects the article on p. 1 in vol. 64.]. PMID- 29009665 TI - A Year's Record of Kata-Thermometer Readings at Rangoon. PMID- 29009666 TI - Quinine Abscesses. PMID- 29009668 TI - Neosalvarsan. PMID- 29009667 TI - The Yellow Fever Danger. PMID- 29009669 TI - Kala-Azar in Bijnor. PMID- 29009670 TI - Proceedings of a Conference Held at Birnagar (Bengal), the 24th February, 1929, to Discuss the Problem of Malaria Control at Birnagar. PMID- 29009671 TI - A Benign Spinal Tumour. PMID- 29009672 TI - The Carnivorous Habits of Indian "Blood-Worms". PMID- 29009673 TI - Ascaris Infection Simulating Bright's Disease. PMID- 29009674 TI - Notes on Current Topics. PMID- 29009675 TI - A Review of Malaria during 1928 in a Minor Hill Station in the Punjab. PMID- 29009676 TI - The Use of Pneumococcus Immunogen Combined in the Treatment of Pneumonia. PMID- 29009677 TI - The Life-History of Entamoeba Histolytica. PMID- 29009678 TI - On the Rationale of Treatment of Carcinoma of the Cervix Uteri. PMID- 29009679 TI - The Intensive Treatment of Kala-Azar by Neostibosan; Part II. PMID- 29009680 TI - Preventive Surgery. PMID- 29009681 TI - Melaena and Haematemesis in the New Born. PMID- 29009684 TI - Medical News. PMID- 29009682 TI - Mental Hygiene in India. PMID- 29009685 TI - Service Notes. PMID- 29009683 TI - Binding of Indian Medical Gazette Volumes. PMID- 29009686 TI - Standardised Lives and Their Assessment in Life Insurance. PMID- 29009687 TI - A Case of Abscess of the Iris. PMID- 29009688 TI - Kurchi Bismuthous Iodide, Its Value in the Treatment of Chronic Amoebic Infections of the Bowel. PMID- 29009689 TI - A Comparative Study of the Effect of Climate and of the Seasons on Body Weight in Pulmonary Tuberculosis in Different Countries. PMID- 29009692 TI - Observations on the Excretion of Alcohol in the Cerebro-Spinal Fluid and Urine after Oral Administration. PMID- 29009691 TI - The Treatment of Seasickness. PMID- 29009690 TI - A List of the Species of Mosquitoes Collected in the French Settlements in India. PMID- 29009693 TI - A Case for Diagnosis. PMID- 29009694 TI - The Use of Pneumococcus Immunogen Combined in the Treatment of Pneumonia. PMID- 29009695 TI - The Effect of Tetronal on the Production of Haematoporphyrin in the Urine. PMID- 29009696 TI - Retention of Urine in Blackwater Fever. PMID- 29009698 TI - Service Notes. PMID- 29009697 TI - Temporary Insanity Following an Attack of Malaria. PMID- 29009699 TI - Medical News. PMID- 29009700 TI - Goitre in Multan District. PMID- 29009701 TI - Local Anaesthesia by Apothesine in General Surgery. PMID- 29009702 TI - The Vital Capacity of the Lungs. PMID- 29009703 TI - Cerebral Symptoms Caused by Plasmodium Vivax. PMID- 29009704 TI - A Case of Diverticulum of the OEsophagus. PMID- 29009706 TI - A Note on Cholera in Infants. PMID- 29009705 TI - Records of Anophelines from the Bengal Dooars. PMID- 29009707 TI - Preventable Blindness in India. PMID- 29009709 TI - A Case of Accidental Poisoning with Barium Sulphide. PMID- 29009708 TI - The Erythrocyte Sedimentation Test in Leprosy. PMID- 29009710 TI - Notes on Current Topics. PMID- 29009711 TI - Notes on a Case of Human Hermaphrodite. PMID- 29009712 TI - Some Cases of Bacillus Coli Bacilluria. PMID- 29009713 TI - A Case of Staphylococcal Septicaemia. PMID- 29009714 TI - Khaki Drill and Skin Irritation. PMID- 29009715 TI - Notes on Current Topics. PMID- 29009717 TI - A Persian Treatment for Oriental Sore. PMID- 29009716 TI - Pathological Laughing and Crying. PMID- 29009718 TI - A Case of Rat-Bite Fever. PMID- 29009719 TI - Ascariasis Simulating Abdominal Tumours. PMID- 29009720 TI - Nervous Manifestations in Tuberculous Infections. PMID- 29009721 TI - X-Ray Work in Baluchistan. The New X-Ray and Electrotherapy Department of the C. M. S. Hospital, Quetta. PMID- 29009722 TI - The Importance of Refractometry in Clinical Research. PMID- 29009723 TI - Chemotherapeutic Investigations with Antimony Preparations in the Experimental Kala-Azar of the Hamster. PMID- 29009724 TI - A Radical Cure for Hydrocele by Quinine Injection. PMID- 29009726 TI - Medical News. PMID- 29009725 TI - A Case of an Abscess of the Brain. PMID- 29009727 TI - Vomiting of "Bees". PMID- 29009728 TI - A Malaria Survey of Madarihat and Its Environs. PMID- 29009729 TI - Blood Pressure in Indians. PMID- 29009730 TI - Microscopic Diagnosis of Malaria on a Group of Tea Estates. PMID- 29009731 TI - Undescended Testis as a Cause of Physical Rejection. PMID- 29009732 TI - Webster's Operation for Entropion of the Upper Lid. PMID- 29009733 TI - Notes on the New Conceptions of Sciatic Pain and on Its Treatment. PMID- 29009734 TI - A Case of Accidental Suffocation in a Well. PMID- 29009735 TI - A Coat Effect Observed in Mice When Fed with Fats under Certain Conditions. (A Preliminary Note). PMID- 29009736 TI - Chaulmoogra Oil in the Treatment of Trachoma. PMID- 29009737 TI - Maternal Mortality in India: A Preliminary Study. PMID- 29009738 TI - Service Notes. PMID- 29009740 TI - The Parasitology of Indian Malaria. Unpublished Information. PMID- 29009739 TI - A Suggested Measure in the Control of Plague. PMID- 29009742 TI - Notes on Current Topics. PMID- 29009741 TI - A Case of Variola Treated by Vaccination. PMID- 29009743 TI - A Case of Induced Poly-Leucocythaemia. PMID- 29009744 TI - Paris Green as an Anopheline Larvicide. PMID- 29009745 TI - Service Notes. PMID- 29009747 TI - The Need for a Therapeutic Substances Act for India. PMID- 29009746 TI - Intravenous Pituitrin. PMID- 29009748 TI - Radiological Examination of the Liver in Cases of Suspected Amoebic Abscess. PMID- 29009750 TI - A Case of Free Bile in the Peritoneal Cavity. PMID- 29009749 TI - Educational Cinema Films. PMID- 29009751 TI - Intravenous Iodine. PMID- 29009752 TI - The Title of "Doctor". PMID- 29009753 TI - Dangerous Blood Donors. PMID- 29009754 TI - Medical News. PMID- 29009757 TI - Myiasis in Lepers. PMID- 29009755 TI - Corrigendum. AB - [This corrects the article on p. 252b in vol. 64.]. PMID- 29009756 TI - A Preliminary Note on a Colour Reaction for " 693 " and Its Application in the Estimation of That Compound in the Urine. PMID- 29009758 TI - An Obscure Neurological Case Simulating Early Leprosy. PMID- 29009759 TI - A Case of Myiasis of a Carious Tooth. PMID- 29009760 TI - Acute Amoebic Dysentery Treated by Hedyotes Auriculares, N. O. Rubiaceae. PMID- 29009761 TI - Simple Tests for Stock Solutions of Quinine and Potassium Iodide. PMID- 29009762 TI - A Case of Ectopic Gestation. PMID- 29009763 TI - Herpes Zoster and Varicella. PMID- 29009764 TI - Medical Science in India. PMID- 29009765 TI - The Valuation of Charas. PMID- 29009766 TI - Encephalitis Lethargica-A Brief Description of the Disease, with Short Notes on the Post-Encephalitic Lethargic Cases Treated at the Ranchi Indian Mental Hospital. PMID- 29009767 TI - Electro-Coagulation (Surgical Diathermy) in Multiple Angiomata of the Head. PMID- 29009768 TI - The Species Distribution of Hookworms in India. PMID- 29009769 TI - The Sterilization of Hypodermic Syringes. PMID- 29009770 TI - The Treatment of Acute Vaginismus. PMID- 29009771 TI - The Superimposed Blood Agar Slope. PMID- 29009772 TI - Leprous Reaction. PMID- 29009773 TI - Isolation of the Antineuritic Vitamin. PMID- 29009774 TI - The Treatment of Acute Vaginismus. PMID- 29009775 TI - An Analysis of 675 Cases of Puerperal Morbidity Treated in the Rotunda Hospital, Dublin. PMID- 29009776 TI - Three Cases of Combined Leprosy and Dermal Leishmaniasis. PMID- 29009777 TI - Perthe's Disease. PMID- 29009778 TI - The Parasitology of Malaria: An Appeal for Information. PMID- 29009779 TI - Unusual Intra-Uterine Tumours. PMID- 29009781 TI - Medical News. PMID- 29009780 TI - Notes on Current Topics. PMID- 29009782 TI - The Treatment of Acute Vaginismus. PMID- 29009783 TI - The Use of Fibrolysin in Leprosy. PMID- 29009784 TI - Unusual Displacements of the Epiphysis of the Patella. PMID- 29009785 TI - Lobar Pneumonia with Intermittent Temperature. PMID- 29009786 TI - Haemoplastin. PMID- 29009787 TI - A Case for Diagnosis. PMID- 29009788 TI - The Importance of Secondary Infections in the Causation of Filarial Lymphangitis. PMID- 29009789 TI - A Case of Elephantiasis Cured by Arrhenol. PMID- 29009790 TI - Service Notes. PMID- 29009791 TI - Tetrachlorethylene in the Treatment of Hookworm Disease. PMID- 29009792 TI - A District's Scheme for Cholera Control. PMID- 29009793 TI - Avertin Rectal Narcosis. PMID- 29009794 TI - The Spleen. PMID- 29009795 TI - A Case for Diagnosis. PMID- 29009796 TI - The Sterilization of Hypodermic Syringes. PMID- 29009797 TI - A Distended Bladder Simulating a Full-Term Uterus. PMID- 29009798 TI - Indigenous Medicine and District Boards. PMID- 29009799 TI - Tabes Dorsalis in an Indian. PMID- 29009800 TI - Exercise in the Tropics. PMID- 29009801 TI - A Case of Foreign Body in the Vagina. PMID- 29009802 TI - Nerve Abscess in Leprosy. PMID- 29009803 TI - Notes on Current Topics. PMID- 29009804 TI - An Interesting Case. PMID- 29009805 TI - An Interesting Case of Melaena and Haematemesis in a Newly-Born Baby. PMID- 29009806 TI - A Case of Amyotrophic Lateral Sclerosis in an East Indian. PMID- 29009807 TI - A Case of Acholuric Jaundice. PMID- 29009808 TI - The Continuous Administration of Saline per Rectum. PMID- 29009810 TI - Service Notes. PMID- 29009809 TI - A Medical Council in India. PMID- 29009811 TI - Caesarean Section. Some Types and Their Uses. PMID- 29009812 TI - A Preliminary Note on the Action and Uses of Pseudo-Ephedrine. PMID- 29009813 TI - Plasmoquine. PMID- 29009814 TI - Report on the Investigation of an Outbreak of Epidemic Dropsy in Rangoon in the Year 1924. PMID- 29009815 TI - A New Test for Albumin in Urine. PMID- 29009816 TI - Post Encephalitic Parkinsonism. PMID- 29009817 TI - Seven Cases of Diaphysial Aclasis (Multiple Exostosis) in Indians, Including Four Cases from One Family. PMID- 29009818 TI - Supplement:-The Indian Medical Year, 1928. PMID- 29009819 TI - Service Notes. PMID- 29009820 TI - A Further Note on the Action of Haemoplastin. PMID- 29009822 TI - A Case of Medico-Legal Interest. PMID- 29009821 TI - Subcutaneous Injection of Oils or Oily Preparations. PMID- 29009823 TI - A Case of Hyperpyrexia for Diagnosis. PMID- 29009824 TI - A Simple Rat Trap. PMID- 29009825 TI - A Note on the Anopheline Fauna of a Small Tank Throughout the Year. PMID- 29009826 TI - A Case of Suppression of Urine. PMID- 29009828 TI - A Case for Diagnosis. PMID- 29009827 TI - Corrigendum. AB - [This corrects the article on p. 199 in vol. 64.]. PMID- 29009829 TI - Notes on the Value of the Sedimentation Test in the Treatment of Leprosy. PMID- 29009830 TI - A Case of Acute Vaginismus. PMID- 29009831 TI - A Case of Valvulus of the Large Intestine at the Splenic Flexure. PMID- 29009832 TI - Erratum: A Case for Diagnosis. (Corrigendum). AB - [This corrects the article on p. 118b in vol. 64.]. PMID- 29009833 TI - Medical News. PMID- 29009834 TI - A Note on the Value of Medicinal Treatment in Cholera. PMID- 29009835 TI - The Sterilization of Syringes. PMID- 29009836 TI - A Simple Method for the Estimation of Blood Urea Applicable at the Bedside. PMID- 29009838 TI - Recent Researches on the Filtrable Viruses. PMID- 29009837 TI - Results of Experiments with Crude Oil Products of the Burma Oil Co., Ltd., Rangoon: As Larvicide. PMID- 29009839 TI - Some Reflections on Obstetrics and Gynaecology during 1928. PMID- 29009840 TI - Roundworm Infection Simulating Appendicitis. PMID- 29009841 TI - "Cooly Itch." A purulent folliculitis due to the Trichophyton violaceum variety Indicum. PMID- 29009842 TI - Accidental Suffocation in a Well. PMID- 29009843 TI - A Huge Ovarian Cyst. PMID- 29009844 TI - Experiments with Isotex as a Larvicide. PMID- 29009845 TI - Notes on Current Topics. PMID- 29009846 TI - A Case of Typhoid Fever, Relapse, Toxaemic Collapse and Recovery. PMID- 29009847 TI - Tiger Bites and Their Treatment. PMID- 29009848 TI - Notes for Staff Engaged on Anti-Malarial Work. PMID- 29009849 TI - A Further Case of Diaphysial Aclasis, (Multiple Exostosis) with a Marked Family History. PMID- 29009850 TI - Sudden Deaths in Young Females. PMID- 29009851 TI - Chologen Treatment for Cholelithiasis. PMID- 29009852 TI - Mutation of Cholera-Like Vibrios under the Action of Bacteriophage: Lysability of Cholera-Like Vibrios by Pure-Line Races of Cholera Bacteriophage and Changes Induced in the Serological Reactions of Cholera-Like Vibrios under the Influence of Bacteriophage. PMID- 29009853 TI - On the Presence of a Filarial Worm in a Tumour Removed from the Left Side of the Nose of a Child. PMID- 29009854 TI - Service Notes. PMID- 29009856 TI - Plasmoquine and Malaria Control. PMID- 29009855 TI - The Curative Value of a Locally-Prepared Sample of Sulpharsenobenzene. PMID- 29009858 TI - Abbreviations and Symbols. PMID- 29009857 TI - A Theory of the AEtiology and Epidemiology of Kala-Azar in India. PMID- 29009859 TI - Indian Species of Artemesia. PMID- 29009860 TI - Cocoanut Milk as an Anthelmintic. PMID- 29009861 TI - Ectopia Vesicae. PMID- 29009862 TI - The Threat to Medical Organisation in India. PMID- 29009864 TI - A Case of Multiple Osteomata. PMID- 29009863 TI - Notes on the Diagnosis and Treatment of Ulcus Tropicum. PMID- 29009866 TI - Notes on Current Topics. PMID- 29009865 TI - Vaccination and Whooping Cough. PMID- 29009867 TI - The Treatment of Ascariasis. PMID- 29009868 TI - Further Observations on the Effect of Opium on Blood Sugar. PMID- 29009869 TI - A Case of Aleukaemic Myelosis. PMID- 29009870 TI - Further Note on Anti-Malarial Measures on the Travancore Tea Companies' Estates. PMID- 29009871 TI - A Short Clinical Note on Tincture of Ephedra as a Cardiac Stimulant. PMID- 29009873 TI - Medical News. PMID- 29009872 TI - A Case of Prematurity with Extreme Deficiency in Weight. PMID- 29009874 TI - Tropical Typhus. PMID- 29009876 TI - Removal of Foreign Bodies from the OEsophagus by External Manipulation. PMID- 29009877 TI - An Improved Type of Obstetric Bedstead. PMID- 29009878 TI - Landry's Paralysis in an Infant. PMID- 29009879 TI - Observations on the Composition of Human Milk in Burma. PMID- 29009880 TI - The Relation of Acetonaemia to Juvenile Ill-Health in India. PMID- 29009881 TI - Notes on Current Topics. PMID- 29009882 TI - A Malaria Survey in Noakhali District, Bengal. PMID- 29009883 TI - 'Aolan' Treatment in Corneal Ulcer and Corneal Opacity. PMID- 29009884 TI - Economic Value of Medical Institutions. PMID- 29009885 TI - Ovarian Tumours. A Ten Years' Record of 547 Cases. PMID- 29009886 TI - Effect of Milk Injections in Gonorrhoeal Disease of Joints. PMID- 29009887 TI - Service Notes. PMID- 29009888 TI - A Somewhat Unusual Case of Algid Malaria. PMID- 29009889 TI - The 'Control' of Malaria with Special Reference to Treatment. PMID- 29009890 TI - Scarlet Fever in Bombay. PMID- 29009891 TI - Note on the Determination of the Nitrogen in Sour Milk as a Subsidiary Standard of Purity. PMID- 29009892 TI - Round Worm Infection Simulating Acute Peritonitis. PMID- 29009894 TI - Medical News. PMID- 29009893 TI - Infantile Biliary Cirrhosis and Artificial Feeding of Infants in India. PMID- 29009895 TI - A Preliminary Note on the Actions and Uses of 'Alepol'. PMID- 29009896 TI - Opium and Albuminuria. PMID- 29009897 TI - A Case of Patent Ductus Arteriosus with Infective Endocarditis. PMID- 29009898 TI - Corrigendum. AB - [This corrects the article on p. 671 in vol. 65.]. PMID- 29009899 TI - Enterococcus Infection. PMID- 29009900 TI - Notes on Current Topics. PMID- 29009901 TI - Corrigenda. AB - [This corrects the article on p. 567 in vol. 65.][This corrects the article on p. 57 in vol. 66.][This corrects the article on p. 24 in vol. 66.]. PMID- 29009902 TI - A Case of Acute Glossitis. PMID- 29009903 TI - Some Observations on Human Amoebiasis : Being an Analysis of Post-Mortem Findings in 426 Cases. PMID- 29009904 TI - The Results of Prophylactic Cholera Inoculation in Faridpur District. PMID- 29009906 TI - Tuberculosis in Animals and Man. PMID- 29009905 TI - Necrosis of the Mandible Following One of the Exanthemata. PMID- 29009907 TI - Modified Enterica Following Inoculation. PMID- 29009908 TI - Heart Affections in Bengali Babies: Case Records. PMID- 29009909 TI - Lizards and Malaria. PMID- 29009910 TI - A Case of Pernicious Anaemia of Pregnancy. PMID- 29009911 TI - Erratum: Minor Surgery and Bandaging. AB - [This corrects the article on p. 724a in vol. 65.]. PMID- 29009912 TI - British Spas: Their Waters and Methods of Treatment: An Extract from Lectures Given in the University of London. PMID- 29009913 TI - Epidemic Dropsy in a Family at Sandwip Island. PMID- 29009915 TI - An Interesting Case of Round-Worm Infection. PMID- 29009914 TI - Intravenous Quinine in Malaria. PMID- 29009916 TI - On the Analysis of the More Commonly Used Ointments of the 'British Pharmacopoeia' Containing an Inorganic Principle as the Active Constituent. PMID- 29009917 TI - Service Notes. PMID- 29009918 TI - A Case of Echis Bite. PMID- 29009919 TI - A Case of Bullet Wound. PMID- 29009920 TI - Unsuspected Sources of Leprous Infection. PMID- 29009921 TI - Pterygium Director. PMID- 29009922 TI - A Case of Appendicular Abscess. PMID- 29009923 TI - Four Cases of Plague Treated with 'Bayer 205'. PMID- 29009924 TI - Medical News. PMID- 29009926 TI - Mathematics and Medical Research. PMID- 29009925 TI - The Existence of Hilum Tuberculosis in Indians. PMID- 29009927 TI - Icterus Index: Its Significance in the Surgery of the Biliary Tract. PMID- 29009929 TI - Notes on Current Topics. PMID- 29009928 TI - Syphilitic Diseases of the Eye. PMID- 29009930 TI - A Case of Embryonal Carcinoma of the Testis. PMID- 29009931 TI - A Case of Osteogenesis Imperfecta (Fragilitas Ossium). PMID- 29009932 TI - Service Notes. PMID- 29009933 TI - Fads and Fashions in Indigenous Medicine. PMID- 29009934 TI - On the Presence of a Filarial Worm in a Tumour Removed from the Left Side of the Nose of a Child. PMID- 29009935 TI - Seasonal Variations of Cholera Bacteriophage in Natural Waters and in Man, in Calcutta during the Year 1930. PMID- 29009937 TI - The International Viewpoint in Leprosy. PMID- 29009936 TI - Injection Treatment of Hydrocele. PMID- 29009938 TI - A Simple Method for Filling Ampoules. PMID- 29009939 TI - An Investigation of the Short Fevers at Trimulgherry, 1931. PMID- 29009940 TI - Seasonal Variations of Dysentery Bacteriophages in Natural Waters and in Man, in Calcutta during the Year 1930. PMID- 29009941 TI - The Roentgenological Diagnosis of Tuberculous Disease of the Lung, in Adults and Children. PMID- 29009943 TI - A Note on the Production of a Cyanogen Radical in Peptone-Water Cultures of Cholera Vibrio. PMID- 29009942 TI - Case of Recovery from Cobra Bite. PMID- 29009944 TI - A Case of Vesical Calculi. PMID- 29009945 TI - Another Note on Stovarsol. PMID- 29009947 TI - An Investigation into the Clogging of the Filter Beds at Topchanchi Waterworks during Hot Weather. PMID- 29009946 TI - Seasonal Variations of Typhoid Bacteriophage in Natural Waters and in Man, in Calcutta during the Year 1930. PMID- 29009948 TI - Effect of Milk Injections on Traumatic Synovitis. PMID- 29009949 TI - A Thread Ligature Round the Penis. PMID- 29009951 TI - Medical News. PMID- 29009952 TI - Noise. PMID- 29009950 TI - Notes on the Blood Findings and Results of Treatment in Twenty Cases of Osteomalacia. PMID- 29009953 TI - Report of the Malaria Commission of the League of Nations on Their Indian Tour, 1929. PMID- 29009954 TI - Meningitis as a Complication of Dysentery. PMID- 29009955 TI - A Simple and Cheap Apparatus for the After-Treatment of Club Foot. PMID- 29009956 TI - Result of the Forecast of Cholera, Smallpox and Plague Incidence in India in 1930, and New Forecast for 1931. PMID- 29009957 TI - A Case of Vasomotor Disturbance after an Antimony Injection. PMID- 29009958 TI - Notes on Painless Childbirth and Infant Feeding. PMID- 29009959 TI - Service Notes. PMID- 29009961 TI - Food-Poisoning versus Cholera. PMID- 29009960 TI - A Case of Anomalous Diaphragmatic Movements. PMID- 29009962 TI - Skin-Grafting in Complete Avulsion of the Scalp. PMID- 29009963 TI - Dysphagia and Aphonia as Complications of Malaria. PMID- 29009964 TI - Short Term Fevers in the Punjab. PMID- 29009965 TI - Actinomycotic Lesions of the Skin of the Hands and Feet Due to Actinomyces keratolytica, n. sp. PMID- 29009966 TI - Therapy in Malaria. PMID- 29009967 TI - Treponema vincenti and Bacillus fusiformis as Possible Causative Agents in a Group of Cases Resembling Mild Influenza. PMID- 29009968 TI - Intravenous Iodine. PMID- 29009970 TI - Notes on Current Topics. PMID- 29009969 TI - A Case of Glandular Fever. PMID- 29009972 TI - Corrigenda. AB - [This corrects the article on p. 11 in vol. 66.]. PMID- 29009971 TI - Results of Blood Examinations in Sprue. PMID- 29009973 TI - A Case of Retention of Urine. PMID- 29009974 TI - The Distribution and Treatment of Late Rickets and Osteomalacia in Northern India. PMID- 29009976 TI - Case of Chyluria. PMID- 29009975 TI - Gynaecological Progress. A Post-Graduate Clinical Lecture. PMID- 29009977 TI - A Case of Cellular Emphysema. PMID- 29009978 TI - Theory in Medicine. PMID- 29009979 TI - Case for Diagnosis. PMID- 29009980 TI - A Case of Tonsillar Calculus. PMID- 29009981 TI - How the Strongly Positive Wassermann Cases Should Be Reported. PMID- 29009982 TI - Malaria in Bombay. PMID- 29009983 TI - Intramuscular Quinine in Malaria. PMID- 29009984 TI - Blood Groups and Heredity. PMID- 29009985 TI - Halometric Readings in Indians: A Preliminary Note. PMID- 29009986 TI - Service Notes. PMID- 29009987 TI - A Case of Acute Pulmonary OEdema in an Adult, as the Result of a Scorpion Sting. PMID- 29009988 TI - Notes on Current Topics. PMID- 29009989 TI - Deceased. PMID- 29009990 TI - Notes on Epidemiology with Special Reference to the Role of the Bacteriophage in Public Health. PMID- 29009992 TI - The Romance of Cinchona. PMID- 29009991 TI - A Prophylactic (?) Against Smallpox. PMID- 29009993 TI - Tako Powder in Dysentery. PMID- 29009994 TI - Medical News. PMID- 29009995 TI - The Treatment of Cholera with Bacteriophage. PMID- 29009996 TI - A Plea for the Lower Uterine Segment Caesarean Section. PMID- 29009997 TI - Foetal Ascites. PMID- 29009999 TI - A Case of Tick Typhus in Poona. PMID- 29009998 TI - Notes on Museum Making. II. Detailed Technique of Glycerine Gelatine Mounting. PMID- 29010000 TI - The Frequency of Sprue among Indians in Madras. PMID- 29010001 TI - Intravenous Sodium Bicarbonate in Cases of Nerve-Pain in Leprosy. PMID- 29010002 TI - Impressions of Surgery in America. PMID- 29010003 TI - A Case of Ainhum. PMID- 29010004 TI - An Operation for Utilising the Middle Finger as the 'Trigger' Finger. PMID- 29010006 TI - Notes on Current Topics. PMID- 29010005 TI - Psychological Aspects of Opium Addiction. PMID- 29010007 TI - Weil's Disease in the Andamans. PMID- 29010008 TI - Two Unusual Cases. PMID- 29010009 TI - Habitual Formation of Stone in the Bladder. PMID- 29010010 TI - Carbon Tetrachloride in the Treatment of Taenia Infections. PMID- 29010012 TI - Indian Squills. PMID- 29010011 TI - An Anaerobic Urinal. PMID- 29010013 TI - Group-Specific Substances in the Human Body. PMID- 29010015 TI - The Use of Forceps in England, Two Hundred Years Ago. PMID- 29010014 TI - Calculus Hydronephrosis in a Horse-Shoe Kidney. PMID- 29010016 TI - Medical News. PMID- 29010017 TI - A Case of Primary Sarcoma of the Heart. PMID- 29010018 TI - Two Cases of Irreducible Hernia Relieved by Atropine Sulphate. PMID- 29010019 TI - A Case of Lambliasis. PMID- 29010020 TI - Service Notes. PMID- 29010021 TI - Invasion of the Nasal Cavity by a Leech. PMID- 29010022 TI - Rural Health Work in Travancore State, South India. PMID- 29010023 TI - Non-Specific Protein Therapy. PMID- 29010024 TI - A Case of Gastric Syphilis. PMID- 29010025 TI - A Note on the Use of the Slit-Lamp. PMID- 29010026 TI - A Psychiatric Tour of Europe. PMID- 29010027 TI - Medical News. PMID- 29010028 TI - Tuberculosis Schemes. PMID- 29010029 TI - A Very Early Case of Disseminated Sclerosis. PMID- 29010030 TI - The Problem of Tuberculosis. PMID- 29010031 TI - Two Cases of Drug Dermatitis (Due to the Use of Chrysophanic Acid). PMID- 29010032 TI - Intestinal Obstruction Caused by Retroverted Uterus. PMID- 29010033 TI - The Quinine Policy. PMID- 29010034 TI - A Case of Chronic Mikulicz's Disease of the Right Lachrymal Sac. PMID- 29010035 TI - A Case of Raynaud's Disease. PMID- 29010036 TI - Tetany Following Measles. PMID- 29010037 TI - An Investigation of After-Histories of Sanatorium Patients in India. PMID- 29010038 TI - Diathermy in Pneumonia. PMID- 29010039 TI - Hilum Tuberculosis. PMID- 29010040 TI - Distribution of Quinine in Jhelum District in 1930. PMID- 29010041 TI - Death from Acute Pulmonary OEdema Due to Scorpion Bite. PMID- 29010042 TI - A Case of Myeloid Leukaemia. PMID- 29010043 TI - A Note on the Formation of Leprous Nodules in the Human Skin. PMID- 29010044 TI - The Serum-Formalin Proportion in the Aldehyde Test for Kala-Azar. PMID- 29010046 TI - Two Pneumonia Cases with a Rare Mode of Onset. PMID- 29010045 TI - A Case of Stab Wound of the Heart. PMID- 29010047 TI - Medical Education. PMID- 29010048 TI - Pellagra in the Deccan: A Report on 40 Cases Occurring among Lepers at the Leprosy Hospital, Dichpali, Hyderabad, Deccan. PMID- 29010049 TI - A Case of Habitual Formation of Stone in the Bladder. PMID- 29010050 TI - Service Notes. PMID- 29010051 TI - Infantile Biliary Cirrhosis and Artificial Feeding of Infants in India. PMID- 29010052 TI - Five Cases of Juvenile Megalocolon. PMID- 29010053 TI - A Scheme for Carrying out a Tuberculosis Survey with a View to the Prevention of the Disease in a Locality. PMID- 29010055 TI - Notes on Current Topics. PMID- 29010054 TI - Angioneurotic OEdema. PMID- 29010057 TI - A Case of Myiasis of the Nasal Cavity. PMID- 29010056 TI - A Note on the Toxic Symptoms Produced by Eating the Seeds of Pithecolobium Bigeminum. PMID- 29010058 TI - Guinea-Worm in a Boy Aged 2. PMID- 29010059 TI - A Case of Acute Pulmonary OEdema in an Adult, as the Result of a Scorpion Sting. PMID- 29010060 TI - Malaria in Bombay. PMID- 29010061 TI - Impressions of a Tour in Europe and America. PMID- 29010062 TI - Complications Due to Round Worms in Gastro-Intestinal Surgery. PMID- 29010063 TI - A Case of Pseudo-Hermaphrodism. PMID- 29010064 TI - Corrigenda. AB - [This corrects the article on p. 118c in vol. 66.]. PMID- 29010065 TI - Death from a Snake Bite (Krait Poisoning). PMID- 29010066 TI - Some Modern Advances in Radiological Diagnosis. PMID- 29010067 TI - Service Notes. PMID- 29010068 TI - Insusceptibility to Vaccination. PMID- 29010069 TI - A Case of Bradycardia. PMID- 29010070 TI - Pelvic Hydronephrosis. PMID- 29010071 TI - Notes on the Treatment of B. coli Infection of the Urinary Tract. PMID- 29010072 TI - An Unusual Focus of B. Typhosus Infection. PMID- 29010073 TI - Contra-Indications in the Use of the Sphygmomanometer. PMID- 29010074 TI - Indian Journal of Tuberculosis. PMID- 29010075 TI - Novasurol in the Treatment of Ascites. PMID- 29010076 TI - Urobilinuria and Its Importance in Malaria. PMID- 29010079 TI - Use of Thymol Iodide in Interstitial Keratitis. PMID- 29010078 TI - A Case of Complete Bilateral Cleft Palate. PMID- 29010077 TI - Rhinosporidium kinealyi Infection. PMID- 29010080 TI - Recent Advances in Infant Feeding. PMID- 29010081 TI - Clinical Experiences with Percain as a Spinal and Local Anaesthetic. PMID- 29010082 TI - The Real Problem in India. PMID- 29010083 TI - Erratum: Halometric Readings in Indians: A Preliminary Note. AB - [This corrects the article on p. 196 in vol. 66.]. PMID- 29010084 TI - A Case of Enterogenous Cyanosis. PMID- 29010086 TI - Notes on Current Topics. PMID- 29010085 TI - The Laboratory Diagnosis of Malaria. PMID- 29010087 TI - Medical News. PMID- 29010088 TI - A Case of Primary Bronchial Carcinoma. PMID- 29010089 TI - The Sanitary Significance of the Presence of Ps. pyocyanea in Water Supplies. PMID- 29010090 TI - A Case of Tetanus. PMID- 29010091 TI - A Case of Strangulated Hernia with Reduction En Bloc. PMID- 29010092 TI - Use of Plasmoquine in Subtertian Malaria: A Note on Bulletin No. 5 of 1930 of the Institute for Medical Research, Federated Malay States, by C. Russell Amies. PMID- 29010094 TI - Note on Stovarsol. PMID- 29010093 TI - A Case of Penetrating Stab Wound of the Abdomen. PMID- 29010095 TI - Calcium Oxalate Calculus in the Urethra. PMID- 29010097 TI - Black Pigmentation on the Skin of the Cheeks and Nose. PMID- 29010096 TI - A Case of Banti's Disease. PMID- 29010098 TI - Notes on a Visit to the Malay Peninsula. PMID- 29010099 TI - Application and Use of Larvicides. PMID- 29010100 TI - A Case of Thrombo-Angiitis Obliterans. PMID- 29010101 TI - An Indian Journal of Tuberculosis. PMID- 29010102 TI - A Unique Case of Elephantiasis of the Labia Minora and Clitoris Associated with Pregnancy. PMID- 29010103 TI - Novocain and Splanchnic Anaesthesia. PMID- 29010104 TI - Notes on the Diagnosis and Treatment of Ulcus Tropicum. PMID- 29010105 TI - Medical News. PMID- 29010106 TI - Quinine Prophylaxis and Other Notes on Malaria. PMID- 29010107 TI - Present International Position for the Prevention of Blindness. PMID- 29010108 TI - The Nature of the Bacterial Substance of an Oral Anti-Dysenteric Vaccine. PMID- 29010109 TI - A Note on the Output and Distribution of Urinary Nitrogen in the Normal Punjabi. PMID- 29010110 TI - Service Notes. PMID- 29010112 TI - Notes on Current Topics. PMID- 29010111 TI - Specific Treatment of Lobar Pneumonia. PMID- 29010113 TI - Insusceptibility to Vaccination. PMID- 29010115 TI - Filariasis (?). PMID- 29010114 TI - A Case of Hypospadias with Double Channel Urethra. PMID- 29010116 TI - Further Observations on Heart Disease in the Punjab. PMID- 29010117 TI - The Manifestations of Chronic Yaws. PMID- 29010118 TI - A Case of Spondylitis Deformans. (Strumpell-Marie Type). PMID- 29010119 TI - Reflex Asthma. PMID- 29010120 TI - Earliest Record of Caesarean Section. PMID- 29010121 TI - Psittacosis or Typhoid Fever? PMID- 29010122 TI - An Unusual Symptom of Round-Worm Infection. PMID- 29010123 TI - The Madras United Twins, Ganga Bai-Gaura Bai. PMID- 29010124 TI - Gangrenous Stomatitis Following the Puerperium. PMID- 29010125 TI - A Fatal Case of Malaria in a Diabetic Subject. PMID- 29010126 TI - Paralysis of the Right Recurrent Laryngeal Nerve Following Carcinoma of Right Breast with Metastasis in the Spine. PMID- 29010128 TI - Torsion of the Ovary on Both Sides. PMID- 29010127 TI - A Case of Erysipelas. PMID- 29010129 TI - Seventh Conference of the International Union against Tuberculosis at Oslo, Norway. PMID- 29010130 TI - A Case of Empyema Thoracis Following Contusion Pneumonia and Its Treatment by Aspiration and Intravenous Iodine Medication. PMID- 29010131 TI - A Subperiosteal Fissured Fracture of the Right Fibula. PMID- 29010132 TI - Clinical Studies in Malaria by Cultural and Enumerative Methods. PMID- 29010133 TI - A Case of Hydatids of the Liver. PMID- 29010134 TI - Rat-Guards for Ships' Hawsers. PMID- 29010135 TI - A Case of 'Tetany' in Typhoid Fever. PMID- 29010136 TI - Irradol, P. D. & Co. PMID- 29010137 TI - Infantile Mortality in Europe. PMID- 29010138 TI - The Diagnosis of Lymphatic Obstruction of Filarial Origin. PMID- 29010139 TI - Two Cases of Myiasis of the Scalp. PMID- 29010140 TI - A Case of Granuloma Inguinale. PMID- 29010141 TI - Spontaneous Haemorrhage in the New Born. PMID- 29010142 TI - An Interesting Case Simulating Tetanus. PMID- 29010143 TI - Notes on Current Topics. PMID- 29010145 TI - A Case of Imperforate Hymen with Retained Menses, Simulating a Uterine Tumour. PMID- 29010144 TI - Obstetric Progress. Post-Graduate Clinical Notes. PMID- 29010146 TI - Abdominal Wounds Treated without Drainage. PMID- 29010147 TI - Three Interesting Cases. PMID- 29010148 TI - An Unusual Complication of Inguinal Hernia. PMID- 29010149 TI - Service Notes. PMID- 29010150 TI - Medical News. PMID- 29010151 TI - Eosinophilia in Dracontiasis. PMID- 29010152 TI - Rheumatic Fever in the Tropics. PMID- 29010153 TI - Anaemia of Pregnancy. PMID- 29010155 TI - Hilum Tuberculosis. PMID- 29010154 TI - Notes on Visit to Bangkok and Siam. PMID- 29010156 TI - Atropine in Cholera. PMID- 29010157 TI - Inherited Stone. PMID- 29010158 TI - Diathermy in Pneumonia. PMID- 29010159 TI - Treatment of Oriental Sore. PMID- 29010160 TI - Service Notes. PMID- 29010161 TI - A Case of Hemiplegia Complicating Typhoid Fever. PMID- 29010163 TI - Oriental Sore. PMID- 29010162 TI - Elixir of Life. PMID- 29010164 TI - Medical News. PMID- 29010166 TI - Notes on Current Topics. PMID- 29010165 TI - Length of Life of Ancylostoma. PMID- 29010168 TI - Mathematics and Medical Research. PMID- 29010167 TI - Haemangiomatous Myo-Fibromata of the Uterus. PMID- 29010170 TI - Notes on Oriental Sore. PMID- 29010169 TI - Novasurol and Salyrgan. PMID- 29010171 TI - Quinine Urethane in a Case of Hydrocoele. PMID- 29010172 TI - The Value of the 'Sergents' Method' for Detecting Malarial Infection in Mosquitoes. PMID- 29010173 TI - Difference in Axillary Temperature on the Two Sides. PMID- 29010174 TI - Coriander Seeds. PMID- 29010176 TI - Report on a Visit to the Leper Island of Culion and on the Anti-Leprosy Work in the Philippine Islands. PMID- 29010175 TI - Notes on Current Topics. PMID- 29010177 TI - A Large Calculus. PMID- 29010178 TI - Yaws (Framboesia) in the Chin Hills. PMID- 29010180 TI - Two Cases Treated with Intravenous Iodine. PMID- 29010179 TI - Notes on a Large Scrotal Hernia Operated upon under Apothesine. PMID- 29010181 TI - Carrel's Treatment and Electrolytic Chlorine as an Antiseptic. PMID- 29010182 TI - A Method of Reducing Dislocations of the Shoulder Joint. PMID- 29010183 TI - A Note on the Disinfestation of Houses by Fumigation with Cresol. PMID- 29010184 TI - A Case of Abdominal Injury. PMID- 29010185 TI - Diabetes and Insulin Treatment in Bengal. PMID- 29010186 TI - A Note on the Treatment of Tropical Ulcer. PMID- 29010187 TI - Service Notes. PMID- 29010188 TI - A Case of Ankylosis of the Knee-Joint Cured by Excision. PMID- 29010189 TI - A Case of Muscular Dystrophy Pseudo-Hypertrophic Type. PMID- 29010190 TI - Sub-Periosteal Excision of Joints. PMID- 29010191 TI - B. Coli Infection in the Puerperim. PMID- 29010192 TI - The Insect Menace. PMID- 29010194 TI - Treatment of Varicose Veins of the Leg by an Occlusion Method. PMID- 29010193 TI - A Case of Vesical Calculus Formed around an Inserted Foreign Body. PMID- 29010195 TI - Vaccination in Rural Areas. PMID- 29010196 TI - Abdominal Tuberculosis in Indian Practice. PMID- 29010197 TI - Tuberculosis Sanatorium Reports. PMID- 29010198 TI - The Medical Education Crisis in Bengal. PMID- 29010199 TI - Intravenous Pituitrin. PMID- 29010200 TI - Canine Leishmaniasis in Bombay. PMID- 29010201 TI - The Medical Aspects of Chemical Warfare. PMID- 29010202 TI - The Art of the Indian Chiropodist. PMID- 29010203 TI - Cellulitis of the Orbit. PMID- 29010204 TI - Notes on Two Cases of Encephalitis Haemorrhagica after Novarsenobillon Administration. PMID- 29010205 TI - A Case of Right-Sided Pleural Effusion Extending into the Epigastrium. PMID- 29010206 TI - Render Unto Caesar That Which Is Caesar's. PMID- 29010207 TI - The Aims of a Medical Man. PMID- 29010209 TI - Post-Graduate Work in Vienna. PMID- 29010208 TI - A Note on the Cultivation of an Entamoeba from a Monkey (Macacus Rhesus). PMID- 29010210 TI - Service Notes. PMID- 29010211 TI - Notes on Current Topics. PMID- 29010212 TI - A Case for Diagnosis. PMID- 29010213 TI - A Note on the Efficacy of Neem-Battis in the Destruction of Rats and Rat Fleas in Rat Burrows. PMID- 29010214 TI - Cholera in Bengal: Past and Present. PMID- 29010215 TI - A Case for Diagnosis. PMID- 29010217 TI - Hints to Medical Motorists. PMID- 29010216 TI - An Interesting Case of Diabetes in Combination with a Condition of Low Kidney Threshold. PMID- 29010218 TI - A Case of Choleraic Dysentery. PMID- 29010219 TI - Preliminary Observations on Acquired Diseases of the Heart and Aorta as Met with in Bengal. PMID- 29010220 TI - The Bengal Ayurvedic and Unani Committees. PMID- 29010221 TI - Cellular Elements in Cholera Stools and Their Relative Importance in Diagnosis of the Disease. PMID- 29010222 TI - Certain Aspects of Litholapaxy. PMID- 29010223 TI - Public Health Organisation. PMID- 29010224 TI - A Case of Kala-Azar with Transposition of the Viscera. PMID- 29010225 TI - Some Points in the Treatment of Typhus Fever. PMID- 29010226 TI - Retention of Urine Due to Hematocolpos. PMID- 29010227 TI - An Unusual Form of Pseudo-Hernia. PMID- 29010228 TI - Four Unusual Surgical Cases. PMID- 29010229 TI - Mercurochrome 220 in the Treatment of Malaria. PMID- 29010230 TI - Notes on Current Topics. PMID- 29010231 TI - Excision of the Pineal Body of a Monkey under Intra-Arterial Anaesthesia. PMID- 29010232 TI - Prevention of Tuberculosis in Children. PMID- 29010233 TI - A Case of Obstructed Labour by an Intra-Uterine Tumour. PMID- 29010234 TI - Acriflavine in Otorrhoea. PMID- 29010235 TI - A Public Health Policy. PMID- 29010236 TI - Application of Extension in Cases of Simple Fracture. PMID- 29010237 TI - An Interesting Sign in Retro-Caecal Appendicitis. PMID- 29010238 TI - Diabetes and Insulin Treatment in Bengal. PMID- 29010239 TI - Proceedings of the International Conference on Health Problems in Tropical America. PMID- 29010240 TI - Cataract Extraction: Notes on 17,000 Operations. PMID- 29010241 TI - The Treatment of Fractures of the Elbow Joint. PMID- 29010242 TI - Service Notes. PMID- 29010243 TI - Treatment of Haemorrhoids by Strangulation and Snipping Method. PMID- 29010245 TI - The Transmission of Dengue Fever. PMID- 29010244 TI - The Midwife in India. PMID- 29010246 TI - A Preliminary Note on the Pharmacology and Therapeutics of Adhatoda Vasica (Basak). PMID- 29010248 TI - Service Notes. PMID- 29010247 TI - Choroidal Haemorrhage Following Cataract Extraction. PMID- 29010249 TI - Observations on the Anti-Diabetic Properties of Cephalandra Indica (Telakucha). PMID- 29010250 TI - Intravenous Anaesthesia in Surgical Practice. PMID- 29010251 TI - An Unusual Effect of Malaria upon the Heart. PMID- 29010252 TI - The Dosage of Anti-Tetanic Serum. PMID- 29010253 TI - Recent Advances in the Operative Treatment of Intestinal Stasis. PMID- 29010254 TI - A Case of Triplets. PMID- 29010255 TI - A Case of Tick Typhus. PMID- 29010256 TI - The Supply of Rural Physicians. PMID- 29010257 TI - A Tumour of the Abdominal Wall. PMID- 29010258 TI - An Obscure Case of Pneumococcal Infection. PMID- 29010260 TI - A Note on the Intravenous Use of Urotropine. PMID- 29010259 TI - Observations on the Treatment of Kala-Azar with Urea Stibamine in the Medical Out Patient Department of the Medical College Hospital, Calcutta. PMID- 29010261 TI - Quinine Plus Alkalies in the Treatment of Malaria. PMID- 29010262 TI - An Unusual Complication of Typhoid Fever. PMID- 29010263 TI - The Preventive Use of Quinine. PMID- 29010264 TI - Erratum: Trichomonas Infection in the Urine. AB - [This corrects the article on p. 160 in vol. 60.]. PMID- 29010265 TI - An Antimony Rash. PMID- 29010266 TI - Intravenous versus Intramuscular Quinine. PMID- 29010268 TI - Notes on Current Topics. PMID- 29010267 TI - Giant Urticaria. PMID- 29010269 TI - A Case of Tetanus. PMID- 29010270 TI - The Value of the Aldehyde Test in the Diagnosis of Kala-Azar. PMID- 29010271 TI - Disorders of Menstruation. PMID- 29010272 TI - A Young Doctor's Views of Old Doctors. PMID- 29010274 TI - A Case of Strangulated Hernia. PMID- 29010273 TI - The Cure of Schistosomiasis by the Intravenous Injection of Antimony Tartrate. PMID- 29010275 TI - Two Cases of Tumour of the Ovary. PMID- 29010276 TI - Stricture of the Ileo-Caecal Valve, and Hyperplasia of the Caecum from Tuberculosis. PMID- 29010277 TI - Calcium Lactate, a Preventative of Still-Births. PMID- 29010278 TI - Intramuscular Quinine. PMID- 29010279 TI - The Treatment of Stiff Joints. PMID- 29010280 TI - An Investigation into the Origin of Cholera Epidemics in the Jheria Coal-Fields. PMID- 29010281 TI - British Income-Tax Refunds. PMID- 29010282 TI - The Causation of Cancer. PMID- 29010283 TI - Diarrhoea in the Breast-Fed Infant. PMID- 29010284 TI - Recollections of the Calcutta Medical College Forty-Five Years Ago. PMID- 29010285 TI - Intravenous Iodine Injections. PMID- 29010286 TI - Erratum: The Beriberi Problem: A Correction. AB - [This corrects the article on p. 1 in vol. 60.]. PMID- 29010287 TI - Leprosy Research. PMID- 29010288 TI - A Case of Pulmonary Embolism. PMID- 29010289 TI - A Case of Traumatic Ptosis. PMID- 29010290 TI - Variations in the Potency of Digitalis Preparations in the Tropics. PMID- 29010291 TI - The Treatment of Asthma. PMID- 29010292 TI - Two Interesting Cases of Post-Typhoid Sequelae. PMID- 29010293 TI - The Short Term Course: Calcutta School of Tropical Medicine. PMID- 29010294 TI - The Migration of Hookworm Larvae in Soil. PMID- 29010296 TI - An Unusual Case of Malaria. PMID- 29010295 TI - Detaining of Patients. PMID- 29010297 TI - Yaws in India. PMID- 29010298 TI - Service Notes. PMID- 29010299 TI - Left-Handedness. PMID- 29010300 TI - Notes on Current Topics. PMID- 29010301 TI - A Useful Method of Adapting an Artificial Eye to a Normal or Reconstructed Socket. PMID- 29010303 TI - Notes on Current Topics. PMID- 29010302 TI - Peracrina versus Malaria. PMID- 29010304 TI - A Case of Accidental Abdominal Injury. PMID- 29010306 TI - The British Social Hygiene Council. PMID- 29010305 TI - The Treatment of Malaria with Peracrina 303. PMID- 29010307 TI - A Note on the Value of Iodine Intravenously in the Treatment of Influenza. PMID- 29010308 TI - Some Points in the Artificial Feeding of Infants. PMID- 29010309 TI - Extra-Uterine Gestation Going to Term with a Living Mother and Child. PMID- 29010311 TI - Some Surgical Cases. PMID- 29010310 TI - Acute Purulent Ophthalmia. PMID- 29010312 TI - Treatment of Kala-Azar. PMID- 29010313 TI - Cases for Diagnosis. PMID- 29010314 TI - Diagnosis in Hospitals. PMID- 29010315 TI - A Case of Hydatid Cyst of the Right Parotid and Submaxillary Glands. PMID- 29010316 TI - Observations on a Fatal Case of Liver Abscess. PMID- 29010317 TI - The Mosquito Factor in the Malaria of Assam Tea Gardens. PMID- 29010318 TI - A Case of Food Sensitiveness. PMID- 29010319 TI - Stone in the Bladder Formed around a Foreign Body. PMID- 29010320 TI - Service Notes. PMID- 29010321 TI - Amputation of the Penis. PMID- 29010323 TI - Chronic Osteomyelitis in Long Bones. PMID- 29010322 TI - Salient Points on Suprapubic Prostatectomy at One Sitting. PMID- 29010324 TI - Indian Diets in Relationship to Health and Disease. PMID- 29010327 TI - The Insect Menace. PMID- 29010326 TI - Cinchona Febrifuge in Malaria. PMID- 29010325 TI - Medical Relief and Medical Education Problems in Bengal. PMID- 29010328 TI - Public Health in Madras Presidency. PMID- 29010329 TI - Clinical Studies on Digitalis in Bengal. PMID- 29010330 TI - Medical Relief in Rural Areas. PMID- 29010331 TI - Haemoplastin in Haemorrhage. PMID- 29010332 TI - Gastro-Jejunostomy with a Bamboo Clamp. PMID- 29010333 TI - Mercurochrome in Malaria. PMID- 29010334 TI - Pharmasol Collo-Calcium. PMID- 29010335 TI - Notes on Current Topics. PMID- 29010336 TI - Sub-Assistant Surgeon's Allowances in Bengal. PMID- 29010337 TI - A Case of Intestinal Obstruction into the Fossa Duodeno-Jejunalis. PMID- 29010339 TI - The Medical Research Council. PMID- 29010338 TI - Von Heyden 471. PMID- 29010340 TI - Service Notes. PMID- 29010341 TI - Thyroid Extract in the Treatment of Nephritis. PMID- 29010342 TI - The Treatment of Malaria in Pregnant Women. PMID- 29010343 TI - Two Cases of Tetanus Treated by Injections of Magnesium Sulphate and Carbolic Acid. PMID- 29010344 TI - Is Trichomonas Hominis Pathogenic? PMID- 29010345 TI - Combined Carbon Tetrachloride and Oil of Chenopodium in the Treatment of Hookworm Disease: A Report on the Treatment of 70 Cases. PMID- 29010346 TI - A Case of Acute Gastro-Duodenal Ileus. PMID- 29010347 TI - Puerperal Sepsis. Its Differentiation and Treatment: A Clinical Lecture to Post Graduates. PMID- 29010348 TI - Trichomonas Infection in the Urine. PMID- 29010349 TI - A Case of Recurring and Encysted Vesical Calculus. PMID- 29010350 TI - An Interesting Case of Oriental Sore. PMID- 29010351 TI - Intravenous Injections of Sodium Iodide in the Treatment of Goitre. PMID- 29010352 TI - On the Technique and Significance of the Rosindole Reaction, Applied to Urine. PMID- 29010353 TI - Medical Relief in Rural Areas. PMID- 29010354 TI - The Treatment of Cholera by Cresol and Acid. PMID- 29010355 TI - A Note on the Outdoor Organisation of the Asansol Mines Board of Health. PMID- 29010357 TI - The Cause of Cancer. PMID- 29010356 TI - A Case of Generalised Blastomycosis. PMID- 29010358 TI - Acute Inflammation of the Prostate. PMID- 29010359 TI - Interesting Effect of an Insect Bite. PMID- 29010360 TI - A Summary of the Results of Autopsies Held at the Calcutta Police Morgue during 1923-1924 on Cases of Sudden Death. PMID- 29010361 TI - A Case of Echis Carinatus (?) Poisoning Failure of Calcium as a Therapeutic Agent. Death in 861/2 Hours. PMID- 29010362 TI - A Case of Arsenical Intolerance? PMID- 29010364 TI - An Interesting Case of Naevus. PMID- 29010363 TI - The Cancer Problem. PMID- 29010365 TI - A Case of Ovariotomy. PMID- 29010366 TI - Pathological Evidence Bearing on Disease Incidence in Calcutta. PMID- 29010367 TI - Accidental "Marking-Nut" Dermatitis. PMID- 29010368 TI - A Fatal Case of Snake-Bite (? Echis Carinatus) during Pregnancy. PMID- 29010369 TI - The Transmission and Etiology of Dengue: A Critical Review. PMID- 29010370 TI - Notes on Current Topics. PMID- 29010372 TI - Service Notes. PMID- 29010371 TI - Indian Science Congress. PMID- 29010373 TI - The Staphylococcal Kidney in Childhood. PMID- 29010374 TI - A Case of Arsenical Intolerance. PMID- 29010375 TI - A Note on the Toxic Symptoms of Organic Arsenic. PMID- 29010376 TI - A Case of Large Ovarian Cyst Not Obstructing Delivery of a Child. PMID- 29010377 TI - Stibosan (Von Heyden "471"). PMID- 29010378 TI - Leprosy Relief Fund. PMID- 29010379 TI - Lichen Spinulosus. PMID- 29010380 TI - A Case of Melanoderma. PMID- 29010381 TI - A Case of Cobra Bite Successfully Treated with Fitz-Simson's Polyvalent Anti Venomous Serum. PMID- 29010383 TI - Izal in Cholera. PMID- 29010382 TI - Fungo-Spirochaetal Affections of Respiratory Passages. PMID- 29010384 TI - A Fatal Case of Snake-Bite (? Echis Carinatus). PMID- 29010385 TI - Soil Acidity and Survival of Hookworm Larvae. PMID- 29010386 TI - A Case of Volvulus of the Ileum. PMID- 29010387 TI - Asepsis. PMID- 29010388 TI - Thyroid Extract in the Treatment of Nephritis. PMID- 29010389 TI - Experiments in Air Embolism. PMID- 29010390 TI - A Case of Internal Strangulation by the Spermatic Cord. PMID- 29010391 TI - "Stibosan" (Von Heyden "471") in Private Practice. PMID- 29010392 TI - Intravenous Pituitrin. PMID- 29010393 TI - A Hint on the Transmission of Kala-Azar. PMID- 29010394 TI - A Swallowed Cork-Screw. PMID- 29010395 TI - A Case of Pedunculated Papilloma of the Tongue. PMID- 29010396 TI - A Case of Malignant Pustule. PMID- 29010397 TI - Compression of the Eyeball before Cataract Operation When Escape of Vitreous or Choroidal Haemorrhage Is Apprehended. PMID- 29010399 TI - A Case of Undetected Gunshot Wound. PMID- 29010398 TI - Action of Disinfectants on Microbes: An Interesting Phenomenon. PMID- 29010400 TI - Relapsing Fever and Dysentery. PMID- 29010401 TI - The Ramblings of a Public Health Officer. PMID- 29010402 TI - Notes on Current Topics. PMID- 29010404 TI - Service Notes. PMID- 29010403 TI - The Toxicity of Carbon Tetrachloride to Cats. A Warning. PMID- 29010405 TI - Treatment of Some Abdominal Conditions with Inflation of Oxygen Gas. PMID- 29010406 TI - The Typhus-Like Fevers. PMID- 29010407 TI - "Diagnosis" in Hospitals. PMID- 29010408 TI - Observations on Cases of Dementia Praecox. PMID- 29010409 TI - Gangrene of the Testes after Torsion of the Spermatic Cord. PMID- 29010410 TI - Notes on Some Methods for Diagnosis of Hookworm Infection and for Estimating the Egg Output. PMID- 29010411 TI - Typhus-Like Fever, Probably Tick-Typhus, in Central India. PMID- 29010412 TI - Recent Work on the Diagnosis and Treatment of Tropical Diseases. PMID- 29010413 TI - Indian Tick-Typhus. PMID- 29010414 TI - Gangosa in India. PMID- 29010415 TI - Remarks on the Pathology of the Disease. PMID- 29010416 TI - Intravenous Iodine. PMID- 29010417 TI - Notes on Carbon Tetrachloride as an Anthelmintic. PMID- 29010418 TI - A Case of Contracture of the Mouth. PMID- 29010419 TI - Erratum: Venereal Disease, Its Prevention, Symptoms and Treatment. AB - [This corrects the article on p. 523 in vol. 59.]. PMID- 29010420 TI - Gaucher's Type of Splenomegaly in a Mahratta Village, with a Case Treated by Splenectomy. PMID- 29010422 TI - Supplement. The Indian Medical Year, 1924. PMID- 29010421 TI - Service Notes. PMID- 29010423 TI - Intravenous Iodine. PMID- 29010425 TI - Intravenous Air Embolism. PMID- 29010426 TI - A Case of Muscular Dystrophy, Scapulo-Humoral Type. PMID- 29010424 TI - A Useful Hypodermic Outfit. PMID- 29010427 TI - A Preliminary Note on the Successful Treatment of Kala-Azar with "Stibamine Glucoside". PMID- 29010428 TI - Phenolaine. PMID- 29010430 TI - Service Notes. PMID- 29010429 TI - Intramuscular Quinine. PMID- 29010431 TI - Indigenous Indian Drugs. PMID- 29010432 TI - Chunam Cancer. PMID- 29010434 TI - Stone in the Bladder. PMID- 29010433 TI - The Problem of Epidemic Dropsy and Beriberi. PMID- 29010435 TI - Corrigendum. AB - [This corrects the article on p. 571 in vol. 59.]. PMID- 29010436 TI - Alcohol. PMID- 29010437 TI - Serum Reactions in Syphilis. PMID- 29010439 TI - Notes on Current Topics. PMID- 29010438 TI - A Case of Typhoid Septicaemia without Typhoid Ulcers. PMID- 29010440 TI - The Psychology of Freud. PMID- 29010442 TI - A Disclaimer: Colloid of Calcium. PMID- 29010441 TI - Intestinal Stasis and Cancer in Indians. PMID- 29010443 TI - A Case of Framboesia in the Nicobar Islands. PMID- 29010444 TI - The Treatment of Incisional Sinuses. PMID- 29010445 TI - Multiple Soft Fibromata of the Face. PMID- 29010446 TI - A Simple Cure for Leucoderma. PMID- 29010447 TI - An Unusual Case of Malaria. PMID- 29010448 TI - Notes on Cases of Acute Yellow Atrophy of the Liver. PMID- 29010449 TI - A Critical Review of Dr. C. A. Bentley's "Malaria and Irrigation in Bengal". PMID- 29010451 TI - An Interesting Case of Perineal Fistula. PMID- 29010450 TI - Pneumonia and Cellulitis Treated with Intravenous Iodine. PMID- 29010452 TI - A Case of Malarial Prostatitis with Reflex Retention of Urine. PMID- 29010453 TI - A Case of Pernicious Malaria Treated with Quinine Intravenously. PMID- 29010454 TI - An Interesting Case of Transverse Presentation. PMID- 29010455 TI - The Up-Going Toe. PMID- 29010457 TI - A Case of Malignant Pustule. PMID- 29010456 TI - Bacteriological Study of Stools of 746 Clinical Cholera Cases in Calcutta. PMID- 29010458 TI - The Ancient Systems of Medicine. PMID- 29010459 TI - Syphilitic Dyspnoea Simulating an Asthmatic Fit. PMID- 29010460 TI - A Unique Case of Multiple Neuro-Fibromata. PMID- 29010461 TI - Notes on Current Topics. PMID- 29010462 TI - A Plea for Research in the Treatment of Squint. PMID- 29010463 TI - A New Organic Antimony Compound for the Treatment of Kala-Azar. PMID- 29010464 TI - A Lecture on Blood Sugar and Sugar Tolerance. PMID- 29010465 TI - A Case of Bullet Wound of the Chest Followed by Pleurisy with Effusion. PMID- 29010466 TI - Tincture of Iodine in Dysentery and Diarrhoea. PMID- 29010467 TI - An Enlarged Wandering Spleen Mistaken for an Ovarian Tumour. Splenectomy and Recovery. PMID- 29010469 TI - Intra-Muscular Injection of Urea Stibamine. PMID- 29010468 TI - A Case of Resuscitation after Cessation of the Vital Functions for over 15 Minutes. PMID- 29010470 TI - Pelvic Measurements in Indian Women. PMID- 29010472 TI - Service Notes. PMID- 29010471 TI - A Useful Digitalis Tincture. PMID- 29010474 TI - Some Notes on Latrines and Hookworm Incidence on an Estate, as Diagnosed by the Clayton-Lane Centrifuge. PMID- 29010473 TI - Familial Treatment of the Insane. PMID- 29010475 TI - The Abuse of Emetine. PMID- 29010476 TI - Epidemic Dropsy at Sandwip. PMID- 29010477 TI - A Case of Multiple Stones in the Bladder. PMID- 29010478 TI - Recovery after Apparent Death. PMID- 29010479 TI - Pelvic Inflammatory Diseases and Pyosalpinx: Diagnosis, Pathology and Treatment. PMID- 29010480 TI - A Cataract Family. PMID- 29010481 TI - A Case of Large Parovarian Cyst in a Young Woman. PMID- 29010482 TI - A Case of Extravasation of Urine. PMID- 29010483 TI - A Case of Delayed Labour. PMID- 29010484 TI - The Pernicious Anaemia of Pregnancy. PMID- 29010485 TI - The Production of Oriental Sore in Man by Flagellate Culture of Leishmania Tropica. PMID- 29010487 TI - White Asphyxia in Male Children. PMID- 29010486 TI - Diverticulitis. PMID- 29010488 TI - A Double Intussusception. PMID- 29010489 TI - A Plea for a Thorough Investigation of the Filariasis Problem. PMID- 29010490 TI - The Effects of Bee Venom. PMID- 29010491 TI - Sundry Cases: (1) Keratosis Pharyngis and Laryngis. (2) Long Sojourn of a Foreign Body in OEsophagus. (3) A Case of Liver Abscess Bursting into the Right Lung. PMID- 29010493 TI - A Simple Method for Estimating the Available Chlorine in Bleaching Powder. PMID- 29010492 TI - A Case of Excision of the Elbow Joint. PMID- 29010494 TI - Notes on Current Topics. PMID- 29010495 TI - The Incidence of Intestinal Parasites in a Calcutta Hospital Population. PMID- 29010496 TI - A Case of Blackwater Fever. PMID- 29010497 TI - A Strange Parasite of Man. PMID- 29010498 TI - A Case of Hydramnios. PMID- 29010499 TI - Erratum. AB - [This corrects the article on p. 174 in vol. 62.]. PMID- 29010501 TI - The Imperial Functions of the Hospital for Tropical Diseases, London. An Appeal to India. PMID- 29010500 TI - A Case of Liver Abscess. PMID- 29010502 TI - Self-Inflicted Injuries. PMID- 29010504 TI - Suggestion as a Treatment. PMID- 29010503 TI - A Short Report on Some Therapeutic Investigations Carried out at the Ranchi European Mental Hospital. PMID- 29010505 TI - A New Species of Anopheline A. Pseudojamesi Common in Bengal. PMID- 29010506 TI - A Case of Symmetrical Enchondromata (?) of the Eyelids. PMID- 29010507 TI - Two Cases of Typhus Fever in Kumaon. PMID- 29010508 TI - Arthritis of Both Elbow Joints Following Small-Pox. PMID- 29010509 TI - Filarial Haematuria. PMID- 29010510 TI - A Silver Method of Staining Leishmania Donovani in the Tissues. PMID- 29010511 TI - The Causation of Cystitis. PMID- 29010512 TI - Service Notes. PMID- 29010513 TI - Suggestion as a Remedial Agent. PMID- 29010514 TI - A Case of Nasal Myiasis. PMID- 29010515 TI - Flood and Flush Schemes-Ancient and Modern-With Reference to the Site of the Ancient City of Gour, Malda District, Bengal, and to the Incidence of Malaria. PMID- 29010516 TI - The Causal Organism of Cholera. PMID- 29010517 TI - Preventable Yet Not Prevented. PMID- 29010518 TI - A Study of the Incidence of Tuberculosis in Calcutta as Evidenced by the Von Pirquet Cuti-Reaction. PMID- 29010519 TI - The Deleteriousness of Potable Spirits on the Indian Market. PMID- 29010520 TI - Vaccination and Female Education. PMID- 29010521 TI - Neurasthenia in the Tropics. PMID- 29010522 TI - The Use of Fishes for the Control of Mosquitoes. PMID- 29010523 TI - The Indian Science Congress. PMID- 29010524 TI - The Treatment of Puerperal Sepsis, with Some Notes on the Bacteriology of Puerperal Fever. PMID- 29010526 TI - The Differential Diagnosis of Small-Pox and Chicken-Pox. PMID- 29010525 TI - Supplement. The Indian Medical Year, 1926. A Review. PMID- 29010528 TI - Lathyrism in the Gilgit Agency. PMID- 29010527 TI - A Case of Dermatolysis. PMID- 29010529 TI - Service Notes. PMID- 29010530 TI - Quinine-Urea Injections in Malaria. PMID- 29010531 TI - Comments on the Present Position of the Treatment of Leprosy. PMID- 29010532 TI - The Treatment of Puerperal Eclampsia, with Notes on 220 Cases of Puerperal Eclampsia Treated at the Government Hospital for Women and Children, Madras, during the Years January 1922 to July 1926. PMID- 29010534 TI - Notes on Current Topics. PMID- 29010533 TI - The Country Dai and Her Ministrations. PMID- 29010535 TI - Further Observations upon "Dermal Leishmanoid". PMID- 29010536 TI - A Fatal Case of Infection with Ascaris Lumbricoides. PMID- 29010537 TI - A Case of Acute Glossitis. PMID- 29010538 TI - Neurasthenia in the Tropics. PMID- 29010540 TI - The Future of Malaria Control in India. PMID- 29010539 TI - Pneumoperitoneum. PMID- 29010541 TI - A Case of Genital Atresia. PMID- 29010542 TI - Suppuration of the Middle Ear: Its Causes, Symptoms, Diagnosis and Treatment. PMID- 29010543 TI - Service Notes. PMID- 29010544 TI - A Simple Method of Dealing with Destructive Lesions of the Lids. PMID- 29010545 TI - Beriberi: Its Symptoms and Treatment. PMID- 29010546 TI - A Case for Diagnosis. PMID- 29010548 TI - Notes on Current Topics. PMID- 29010547 TI - A Note on the Parasite of "Dermal Leishmanoid". PMID- 29010549 TI - Medical Education and Registration in India. PMID- 29010550 TI - A Case of Fibroneuroma of the Cauda Equina. PMID- 29010551 TI - Injuries of the Knee-Joint. PMID- 29010552 TI - A Case of Acute Glossitis. PMID- 29010554 TI - The Treatment of Hepatic Abscesses of Amoebic Origin. PMID- 29010553 TI - A Case of Cerebral Abscess Following Ottorrhoea. PMID- 29010555 TI - Intramuscular Quinine in Malaria. PMID- 29010557 TI - Erratum: Thoracic Surgery. The Surgical Treatment of Thoracic Disease. AB - [This corrects the article on p. 630 in vol. 61.]. PMID- 29010556 TI - The Future of Anti-Malarial Research. PMID- 29010558 TI - Ketosis in Acute Fevers. PMID- 29010559 TI - The Dispensary Treatment of Malaria in India. PMID- 29010560 TI - Brief Notes on the Life and Work of Sir Ronald Ross. PMID- 29010562 TI - Notes on Current Topics. PMID- 29010561 TI - A Case of Haematuria. PMID- 29010563 TI - The Value of Injections of Carbolic Acid and Magnesium Sulphate in the Treatment of Tetanus. PMID- 29010564 TI - A Case of Compound Fracture of the Skull. PMID- 29010565 TI - Constants of Pure Cow Ghee. PMID- 29010566 TI - The Incidence of Primary Carcinoma in India as Inferred from Post-Mortem Records of Fifty Years from 1877 to 1926. PMID- 29010567 TI - Spur-Like Projections Met with in Bone Radiography. PMID- 29010569 TI - Surgical Drainage for Ascites. PMID- 29010568 TI - The Geographical Distribution of Some of the Diseases of India. PMID- 29010570 TI - A Preliminary Note on the Action of Antimony Compounds on the Blood Serum. A New Serum Test for Kala-Azar. PMID- 29010571 TI - Wanted a Policy. PMID- 29010572 TI - Intravenous Hexamine in Mumps. PMID- 29010573 TI - Vomiting Caused by Morphia. PMID- 29010575 TI - Medical Education in India. PMID- 29010574 TI - Parotitis as a Complication of Lobar Pneumonia. PMID- 29010576 TI - Service Notes. PMID- 29010577 TI - A Few Important Facts Regarding Manufacture of Soda-Water from the Chalk-Derived Water of a Deep Tube Well. PMID- 29010578 TI - A Case of Surgical Emphysema. PMID- 29010579 TI - The Electrophonoide Method of Treating the Deaf. PMID- 29010580 TI - On the Transmission of Plague by Xenopsylla Astia and X. Cheopis. Preliminary Observations. PMID- 29010581 TI - The Application of Our Knowledge of Tuberculosis to Indian Conditions. PMID- 29010583 TI - The Need for an Indigenous Profession of Dental Surgery in India with a Brief History of the Efforts to Meet It Made under the Auspices of the Madras Medical Department. PMID- 29010584 TI - Notes on Current Topics. PMID- 29010582 TI - A Case for Diagnosis. PMID- 29010586 TI - Luminal-Sodium in the Treatment of Tetanus. PMID- 29010585 TI - The Incidence of Helminthic Infections in the Carmichael Hospital for Tropical Diseases, Calcutta. PMID- 29010587 TI - The More Easily Observed Pathological Changes in the Cerebro-Spinal Fluid, and Their Clinical Interpretations. PMID- 29010588 TI - Urea Stibamine Solution as a Test in Kala-Azar. PMID- 29010590 TI - A Case of Bullet Wound of the Abdomen. PMID- 29010589 TI - The Antimony Test in the Diagnosis of Kala-Azar. PMID- 29010591 TI - The Diagnosis of Gangrene of the Small Intestine and Partial Intestinal Obstruction. PMID- 29010593 TI - A Case of Transposed Viscera. PMID- 29010592 TI - Atropine Sulphate in Strangulated Hernia. PMID- 29010594 TI - Service Notes. PMID- 29010595 TI - The Mofussil Dispensary. PMID- 29010596 TI - The Occipito-Posterior Position: Its Complications and Treatment, with Observations on the Insulin-Glucose Method in Shock. PMID- 29010597 TI - A Case of Intestinal Obstruction. PMID- 29010598 TI - The Treatment of Bubonic Plague by Intravenous Injections of Anti-Plague Serum. PMID- 29010599 TI - The Scope of Collapse Therapy (Artificial Pneumothorax and Thoracoplasty) in the Treatment of Pulmonary Tuberculosis in India. PMID- 29010600 TI - Two Cases of Snake-Bite. A Plea for the More Extensive Use of Antivenene. PMID- 29010601 TI - Some Problems in Rabies. PMID- 29010602 TI - Some Observations on Dysentery in Port Blair, Andaman Islands. PMID- 29010603 TI - Afebrile Cerebral Malaria. PMID- 29010605 TI - Notes on Two Cases of Undiagnosed Fever. PMID- 29010604 TI - A Case of Extensive Scalding. PMID- 29010607 TI - Notes on Current Topics. PMID- 29010606 TI - Kala-Azar at High Altitudes. PMID- 29010608 TI - The Chemistry of the Blood of Normal Healthy Indians and Its Variations in Disease. PMID- 29010609 TI - Difficulties in the Early Diagnosis of the Typhoid Group of Fevers. PMID- 29010610 TI - A Lipoma of the Cheek and Neck. PMID- 29010611 TI - Intermittent Fever in Pneumonia. PMID- 29010612 TI - The Preliminary Excitant Action of Morphia. PMID- 29010613 TI - The Treatment of Myiasis. PMID- 29010614 TI - Intramuscular Sodium Salicylate in Lumbago. PMID- 29010615 TI - Disease of the Gall-Bladder and Gall-Stones. PMID- 29010616 TI - Further Investigations into the AEtiology of Epidemic Dropsy. PMID- 29010617 TI - The Treatment of Tuberculous Joints. PMID- 29010618 TI - The Food Value of the Nut of Trapa Bispinosa. PMID- 29010619 TI - A Case of Foreign Body in the Larynx. PMID- 29010620 TI - Intravenous Iodine in Pneumonia. PMID- 29010621 TI - Kala-Azar in the Simla Hills. PMID- 29010622 TI - An Interesting Case of Malaria. PMID- 29010623 TI - Ascaris Infection as a Cause of Abdominal Colic. PMID- 29010624 TI - A Case of Acute Yellow Atrophy of the Liver. PMID- 29010625 TI - Two Cases of Ascaris Lumbricoides Infection Simulating Cholera. PMID- 29010626 TI - A Case of Cirsoid Aneurysm of the Dorsalis Pedis Artery. PMID- 29010627 TI - A New Serological Test for Kala-Azar. PMID- 29010629 TI - Some Problems in Rabies. PMID- 29010628 TI - Service Notes. PMID- 29010630 TI - A Case of Stiff Jaw after Cancrum Oris-Surgical Interference-Cure. PMID- 29010631 TI - The Germicidal Power of Ethyl Alcohol in Spirits. PMID- 29010632 TI - A Report on Three Cases of Bacillary Dysentery Treated with Bacteriophage. PMID- 29010633 TI - The Sanocrysin Treatment of Tuberculosis with Special Reference to Indian Patients. PMID- 29010635 TI - Two Forms of Infection of the Kidney. PMID- 29010634 TI - A Cystic Tumour of the Mesentery. PMID- 29010636 TI - A New Conception of the Epidemiology and Endemiology of Cholera. PMID- 29010637 TI - A Case of Cerebral Abscess and One of Tuberculous Peritonitis. PMID- 29010638 TI - A Case Typical of Rural Midwifery Practice. PMID- 29010639 TI - A Case of Septicaemia Treated by Intravenous Injection of Iodine. PMID- 29010640 TI - A Note on the Staining of Tubercle Bacilli. PMID- 29010641 TI - An Apparently Infectious Outbreak of the Epidemic Dropsy Form of Beriberi. PMID- 29010642 TI - Radium and the Cure of Cancer. PMID- 29010643 TI - Three Interesting Cases of Malignant Disease. PMID- 29010644 TI - New Light on the Epidemiology of Cholera. PMID- 29010645 TI - Some Observations on the Eruption of Teeth. PMID- 29010647 TI - Erratum: Chemistry and Recent Progress in Medicine. AB - [This corrects the article on p. 572c in vol. 61.]. PMID- 29010646 TI - A Case of Parovarian Cyst. PMID- 29010649 TI - A Case of Angio-Neurotic OEdema. PMID- 29010648 TI - Suspended Animation. PMID- 29010650 TI - A Case of Imperforate Hymen. PMID- 29010652 TI - A Case of Ascaris Infection Simulating Cholera. PMID- 29010653 TI - Service Notes. PMID- 29010651 TI - A Case of Ascites Cured by Permanent Drainage of the Fluid into the Subcutaneous Tissue. PMID- 29010654 TI - A Short Account of the Welsh Mission Hospital, Shillong, and a Resume of Its Work. PMID- 29010655 TI - The Result of Artificial Pneumothorax Treatment in Pulmonary Tuberculosis, with a Synopsis of 182 Cases. PMID- 29010657 TI - A Case of Accidental Abdominal Injury. PMID- 29010656 TI - Notes on Current Topics. PMID- 29010658 TI - A Case of Surgical Emphysema Following Fracture of the 5th and 6th Ribs. PMID- 29010660 TI - A Case of Bilateral Dislocation of the Mandible. PMID- 29010659 TI - Is Epidemic Dropsy an Infectious Disease? PMID- 29010661 TI - Notes in Ophthalmic Practice. PMID- 29010662 TI - Berberine Sulphate in Oriental Sore. PMID- 29010663 TI - The Control of Kala-Azar on Tea Estates. PMID- 29010664 TI - A Case of Large Ovarian Cyst in a Young Woman. PMID- 29010666 TI - Two Interesting Cases of Malaria. PMID- 29010665 TI - A Case of Arsenical Dermatitis Following Injections of Novarsenobillon. PMID- 29010667 TI - An Interesting Case of Fracture of the Skull and Injury to the Brain. Ending in Complete Recovery. PMID- 29010669 TI - Corrigendum. AB - [This corrects the article on p. 596 in vol. 61.]. PMID- 29010668 TI - Gynaecology and Obstetrics. A Practical Survey of Recent Authoritative Opinions. PMID- 29010670 TI - A Note on the Geographical Distribution of Some of the Diseases of India. PMID- 29010672 TI - Notes on Current Topics. PMID- 29010671 TI - Preventive Medicine and Mission Hospitals. PMID- 29010674 TI - Some Observations on Gastric and Duodenal Ulcers in Bengal. PMID- 29010673 TI - The Serum Treatment of Plague. PMID- 29010675 TI - Ostelin. PMID- 29010676 TI - A Case of Rodent Ulcer Cured by Injections of Selenium. PMID- 29010677 TI - Kala-Azar at High Altitudes. PMID- 29010678 TI - Rickets and Infantile Cirrhosis of the Liver. PMID- 29010680 TI - Deep Infiltration Anaesthesia in Ophthalmic Operations. PMID- 29010679 TI - An Analysis of 337 Cases of Oriental Sore Treated by Various Methods. PMID- 29010681 TI - The Possible Pathogenicity of Giardia Intestinalis. PMID- 29010683 TI - Our November 1927 Issue. PMID- 29010682 TI - Indigenous Cases of Malaria at High Altitudes. PMID- 29010684 TI - Some Problems in Rabies. PMID- 29010686 TI - Service Notes. PMID- 29010685 TI - The Woes of an Editor. PMID- 29010688 TI - A Case of Double Monster (Parasitic Foetus). Removal of Parasite, Recovery of Autosite. PMID- 29010687 TI - Quality of Milk of Some Special Breeds of Himalayan Cows. PMID- 29010689 TI - A New Diluent for Paris Green. PMID- 29010690 TI - Problems in Rabies. PMID- 29010691 TI - Joint Symptoms in Typhoid Fever. PMID- 29010692 TI - Some Interesting Cases at the West Hospital, Rajkot. PMID- 29010694 TI - The Need for a Public Health Policy for India. PMID- 29010693 TI - Notes on Two Cases of Alastrim. PMID- 29010695 TI - Indian Public Health. PMID- 29010696 TI - A Case of Caesarian Section for Osteomalacia. PMID- 29010697 TI - Physical Efficiency in Hookworm Infection: A Preliminary Report. PMID- 29010699 TI - A Case of Sweating Blood. PMID- 29010698 TI - Unusual Lesions in Varicella. PMID- 29010700 TI - A New Growth of the Eye. PMID- 29010702 TI - The Treatment of Snake-Bite. PMID- 29010701 TI - Emetine Administration. PMID- 29010703 TI - A Case of Quinine Intolerance. PMID- 29010704 TI - Observations on the Pharmacological Action of Conessine, the Alkaloid of Holarrhena Antidysenterica. PMID- 29010705 TI - Notes on Infantile Cirrhosis of the Liver. PMID- 29010706 TI - A Case of "Typho-Lumbricosis". PMID- 29010707 TI - British Income-Tax Claims. PMID- 29010708 TI - A Case of Opacities of the Lens Occurring as a Sequel to an Attack of Kala-Azar. PMID- 29010709 TI - Intracapsular Extraction of Cataract, Including the Most Recent Advances. PMID- 29010710 TI - Some Aspects of Therapeutics in India. PMID- 29010711 TI - A Case of Dermatitis Exfoliata Cured by the Injection of Urea-Stibamine (Brahmachari). PMID- 29010712 TI - The Treatment of Cholera. PMID- 29010713 TI - The Operative Treatment of Fractures. PMID- 29010714 TI - Advertising by Medical Men. PMID- 29010715 TI - A Case of Tuberculous Disease of the Hip Joint. PMID- 29010716 TI - The Interchange of Health Personnel in Japan under the Auspices of the League of Nations. PMID- 29010717 TI - A Case of Spastic Paraplegia Treated Successfully by Injection of Benign Tertian Malaria. PMID- 29010719 TI - A Fatal Case Associated with Filarial Infection. PMID- 29010718 TI - Vomiting Caused by Morphia: A Note of Warning. PMID- 29010720 TI - He Ceased to Be a Doctor. PMID- 29010721 TI - A Case of Intestinal Obstruction. PMID- 29010723 TI - Service Notes. PMID- 29010722 TI - Pernicious Forms of Malaria at Sompeta, Ganjam District. PMID- 29010724 TI - An Interesting Case of Syphilis. PMID- 29010725 TI - An Analysis of 108 Intravenous Iodine Injections. PMID- 29010726 TI - An Unusual Foreign Body in the Ear. PMID- 29010727 TI - Notes on Current Topics. PMID- 29010729 TI - Treatment by Suggestion. PMID- 29010728 TI - Tropical Typhus. PMID- 29010730 TI - Intravenous Sodium Iodide in Goitre. PMID- 29010731 TI - The Field Distemper Fund. PMID- 29010733 TI - Co-Operation against Disease. PMID- 29010732 TI - Infantile Cirrhosis of the Liver. PMID- 29010734 TI - The Operative Treatment of Fractures. PMID- 29010735 TI - Quinine Urea in Malaria. PMID- 29010736 TI - Mass Treatment for Hookworm Infection on Tea Estates in Assam. PMID- 29010738 TI - A Case of Scorpion Sting. PMID- 29010737 TI - The Anaemia of Pregnancy: An Enquiry Carried out under the Auspieces of the Indian Research Fund Association. PMID- 29010739 TI - A Case of Ovarian Dermoid. PMID- 29010741 TI - A Case of Medico-Legal Interest. PMID- 29010740 TI - Raw Caoutchouc in the Stomach. PMID- 29010742 TI - Two Interesting Cases: Enormous Ovarian Tumour; Enormous Enlargement of the Liver from Secondary Carcinoma. PMID- 29010744 TI - Service Notes. PMID- 29010743 TI - Notes on Current Topics. PMID- 29010745 TI - A Case of Gout in a Burman. PMID- 29010746 TI - A Case of Iron Ring Incarcerated around the Root of the Penis. PMID- 29010747 TI - A Case for Diagnosis: (? Variola or Purpura Haemorrhagica). PMID- 29010748 TI - A Case of Imperforate Anus. PMID- 29010749 TI - An Unusual Case of Raynaud's Disease. PMID- 29010750 TI - The Incubation Period of Kala-Azar. PMID- 29010751 TI - A Case of Ectopic Gestation. PMID- 29010752 TI - Torsion of the Spermatic Cord and Spontaneous Recovery. PMID- 29010753 TI - Plasmochin in the Treatment of Malaria. PMID- 29010754 TI - Counterfeit Drugs. PMID- 29010755 TI - The Use of the Microscope in the Practice of Tropical Medicine. PMID- 29010756 TI - An Epidemic of Dropsy among Indians in Fiji. PMID- 29010757 TI - A Medico-Legal Study of the Calcutta Riots of 1926. PMID- 29010758 TI - A Case of Persistent Tremor of the Head. PMID- 29010759 TI - A Case of Syphilitic Endarteritis Obliterans. PMID- 29010760 TI - Acetylarsan in the Treatment of Syphilis. PMID- 29010761 TI - A Post-Graduate Lecture on the Pathology of Plague. PMID- 29010762 TI - A Preliminary Note on the Treatment of Small-Pox by Intravenous Administration of Potassium Permanganate. PMID- 29010763 TI - Registrable Qualifications. PMID- 29010764 TI - The Anaemia of Pregnancy. A Study of Forty-Three Cases. PMID- 29010765 TI - The Sigmoidoscope as an Aid to Diagnosis in Chronic Dysentery and Its Sequelae. PMID- 29010767 TI - Tropical Dermatology. PMID- 29010766 TI - He Ceased to Be a Doctor. PMID- 29010768 TI - The English Doctor in the Middle Ages. PMID- 29010769 TI - Arthritis Following Small-Pox. PMID- 29010770 TI - The Species of Malaria Parasites. PMID- 29010771 TI - The Auto-Sterilizing Mechanism of the Gastro-Intestinal Tract. (A Note on the Use of Dilute Acids in the Prevention and Treatment of Cholera). PMID- 29010772 TI - The Place of Plasmochin in the Treatment of Malaria. PMID- 29010773 TI - Human Placenta as an Enriching Medium for the Gonococcus. PMID- 29010774 TI - Some Observations on Appendicitis among Indian Women. PMID- 29010775 TI - A Case of Sublingual Abscess. PMID- 29010776 TI - A Case of Typhus Fever in Allahabad. PMID- 29010777 TI - The Differential Diagnosis of Small-Pox and Chicken-Pox. PMID- 29010778 TI - A Short Description of an Epidemic Disease of Children Prevalent in Goa Since 1921. PMID- 29010779 TI - Arthritis of Both Elbow Joints as a Sequel of Small-Pox. PMID- 29010780 TI - An Interesting Phenomenon in a Case of Cleft Palate. PMID- 29010781 TI - Report on Leprosy Survey Work at Manbazar Thana, District Manbhum, Bihar and Orissa. PMID- 29010782 TI - Blackwater Fever and Malaria. PMID- 29010783 TI - Aminostiburia in Kala-Azar. PMID- 29010784 TI - The Differential Diagnosis of Small-Pox and Chicken-Pox. PMID- 29010785 TI - Correspondence. PMID- 29010786 TI - The Ross-To-Manson Letters of 1895-1899; Missing Portions of Two Important Letters. PMID- 29010787 TI - The Treatment of Filarial Fever by Neosalvarsan. PMID- 29010788 TI - Service Notes. PMID- 29010789 TI - Further Observations on the Serum Test for Kala-Azar with Organic Antimony Compounds. A Simple Blood Test for Kala-Azar. PMID- 29010790 TI - A Case of Toxic Heart-Block Due to Cerbera Thevetia (Yellow Oleander Seeds). PMID- 29010791 TI - Gland Puncture Findings in Leprosy. PMID- 29010792 TI - Tinea Cruris: Its Manifestations, Diagnosis and Treatment. PMID- 29010794 TI - Notes on Current Topics. PMID- 29010793 TI - Guinea-Worm Infection: A Personal Experience. PMID- 29010795 TI - A Complication of Operation for Vesical Calculus. PMID- 29010796 TI - Leprosy in the Bengal-Bihar Border Line. PMID- 29010797 TI - Parotitis as a Complication of Lobar Pneumonia. PMID- 29010798 TI - Some Observations on the Value of Iodine in Tuberculosis. PMID- 29010799 TI - A Case of Cystic Palpiloma Arising from the Broad Ligament. PMID- 29010800 TI - The Walking Caliper Splint and Its Uses. PMID- 29010801 TI - Plasmochin in Malaria. PMID- 29010803 TI - Sir Norman Walker's Report on Medical Education in India. PMID- 29010802 TI - The Differential Diagnosis of Small-Pox and Chicken-Pox. PMID- 29010804 TI - Maternal Mortality in Child-Birth in India. PMID- 29010806 TI - Can the Non-Agglutinating Vibrios Be Mutation Forms of the Cholera Vibrio? PMID- 29010805 TI - A Short Note on Mild Small-Pox in Patna. PMID- 29010807 TI - A Preliminary Report of Work Carried out by the Cholera Bacteriophage Enquiry. PMID- 29010809 TI - The Far Eastern Association of Tropical Medicine Congress. PMID- 29010808 TI - Suggestion in Eneuresis. PMID- 29010810 TI - Seborrhoeic Dermatitis or Pityriasis Capitis: A Lesion Caused by the Malassezia Ovale. PMID- 29010811 TI - Notes on Current Topics. PMID- 29010812 TI - Some Aspects of the Pathology of Pernicious Anaemia. PMID- 29010813 TI - Dercum's Disease or Adiposis Dolorosa. PMID- 29010814 TI - Mycetoma. PMID- 29010815 TI - A Case of Abdominal Injury by an Arrow. PMID- 29010816 TI - A Case of Bacillus Coli Infection in an Infant. PMID- 29010817 TI - Malaria Prophylaxis. PMID- 29010818 TI - Leeches in the Throat. PMID- 29010819 TI - Prolapsus Uteri: Its AEtiology, Prevention and Treatment. PMID- 29010821 TI - Service Notes. PMID- 29010820 TI - A Case of OEdema Following Cholera. PMID- 29010822 TI - The Prevention of Infection in Cataract Operations. PMID- 29010824 TI - Dysentery in Burma (Military Stations) with a Note on Some Post-Dysenteric Infections. PMID- 29010823 TI - A Case of Scarlet Fever. PMID- 29010825 TI - A Preliminary Note on the Absorption of 'Makaradhwaja' (Sulphide of Mercury). PMID- 29010827 TI - Current Topics. PMID- 29010826 TI - Rabies in the Mongoose. PMID- 29010828 TI - An Advanced Case of Rickets Treated by Ossin. PMID- 29010829 TI - Service Notes. PMID- 29010830 TI - The Tropical Anaemia of Pregnancy. PMID- 29010832 TI - Medical News. PMID- 29010831 TI - The Infectivity of Milk and Meat in Rabies. PMID- 29010834 TI - The Anaemia of Pregnancy. PMID- 29010833 TI - A Case of Rhinosporidium Polypus in a Hindu Woman. PMID- 29010835 TI - Clinical Studies in Malaria by Cultural and Enumerative Methods. Second Series. PMID- 29010836 TI - Mutation of Cholera Vibrios: The Characters of the Population of a Freshly Isolated Cholera Colony, with a Note on Some Colony Variants of Cholera and Cholera-Like Vibrios. PMID- 29010837 TI - A Case of Stone in the Bladder Presenting a Peculiar Symptom-Complex. PMID- 29010838 TI - Casualties in War. PMID- 29010839 TI - Psychological Aspects of Opium Addiction. PMID- 29010841 TI - Service Notes. PMID- 29010840 TI - Result of the Forecast of Cholera, Smallpox and Plague in India in 1931 and Forecast for 1932. PMID- 29010842 TI - Severe Reaction Following the Injection of Urea-Stibamine. PMID- 29010843 TI - Cases of Tick-Typhus in a Town. PMID- 29010844 TI - An Epidemic of Jaundice in the Alipuram Jail, Bellary (South India). PMID- 29010845 TI - Percain in Spinal Anaesthesia. PMID- 29010846 TI - A New Eyelid Clamp. PMID- 29010848 TI - A Case of Rupture of the Urethra. PMID- 29010849 TI - Neostibosan in Chyluria. PMID- 29010847 TI - A Case of Recurrent Appendicitis with a Large Faecal Concretion. PMID- 29010850 TI - Some Snake-Bite Cases. PMID- 29010851 TI - Indian Ipecacuanha. PMID- 29010852 TI - Current Topics. PMID- 29010853 TI - Medical News. PMID- 29010854 TI - Reactions Following Hydno-Creol Injections. PMID- 29010855 TI - Unusual Types of Primary Lesions in Yaws. PMID- 29010856 TI - Indian Species of Artemesia. PMID- 29010857 TI - Microfilariae in the Sputum. PMID- 29010858 TI - Two Interesting Cases of Malaria. PMID- 29010859 TI - Current Topics. PMID- 29010860 TI - Primary Bronchogenic Carcinoma. PMID- 29010861 TI - The Place of Psychiatry in the Medical Colleges and Schools in India. PMID- 29010862 TI - A Short Account of a Recent Out-Break of Diphtheria at Rajkot, with Special Reference to the Carrier Problem. PMID- 29010863 TI - A Case of Locomotor Ataxia in an Indian. PMID- 29010865 TI - The Biological Assay of Drugs in India. PMID- 29010864 TI - A Case of Acute Endocarditis. PMID- 29010866 TI - Post-Mortem Delivery of a Foetus. PMID- 29010867 TI - Correspondence. PMID- 29010868 TI - The Modern Intracapsular Operation for Senile Cataract. PMID- 29010869 TI - Snake Venoms in Medicine. PMID- 29010870 TI - A Study of the Distribution of Sugar in the Blood of Diabetic and Non-Diabetic Indian Subjects. PMID- 29010871 TI - Changes in Cardiac Rhythm in a Case of Rheumatic Mitral Disease Complicated with Broncho-Pneumonia. PMID- 29010872 TI - Service Notes. PMID- 29010873 TI - The Prevention of Heart Affections in India. PMID- 29010874 TI - A Leech in the Nasal Cavity. PMID- 29010875 TI - An Outbreak of Exfoliative Glossitis in an Assam Jail. PMID- 29010876 TI - Atebrin in Malaria. PMID- 29010877 TI - Avertin Anaesthesia, a Study of 114 Cases. PMID- 29010879 TI - An Unusual Case of Sporotrichosis. PMID- 29010878 TI - A National Drink of the Hill-Folk of Darjeeling. PMID- 29010880 TI - A Case of Severe Enteric-Like Fever Due to Bacillus Alkaligenes. PMID- 29010881 TI - Berberine and Berberine-Containing Plants in Pharmacology and Therapeutics. PMID- 29010883 TI - Current Topics. PMID- 29010882 TI - The Behaviour of Plasmodia in the Mosquito after Treatment of the Human Host with Atebrin. PMID- 29010884 TI - Leprosy in India: The Present Outlook. PMID- 29010886 TI - Atebrin: A Synthetic Drug for the Treatment of Malaria. PMID- 29010885 TI - A Case of Malaria with Cerebellar Localization. PMID- 29010887 TI - Service Notes. PMID- 29010888 TI - Medical News. PMID- 29010889 TI - The Mode of Action of Atropine in the Reduction of Hernia. PMID- 29010890 TI - Anti-Malarial Measures in Travancore. PMID- 29010891 TI - On the Failure of Toddalia Aculeata in the Treatment of Malaria. PMID- 29010892 TI - Bilocular Hydrocele Simulating Hernia and Hydrocele. PMID- 29010893 TI - A Practical Note on the Cyanide Fumigation of Ships. PMID- 29010894 TI - Field Experiments with Atebrin and Plasmochin. PMID- 29010896 TI - Aloin in Pregnancy. PMID- 29010895 TI - A Case of Blackwater Fever Precipitated by Ptomaine Poisoning Due to Unclean Degchies. PMID- 29010898 TI - The Profession of Pharmacy. PMID- 29010897 TI - Correspondence. PMID- 29010899 TI - A Case of Dermatolysis. PMID- 29010900 TI - A Case of Blackwater Fever Treated by Atebrin. PMID- 29010901 TI - The Treatment of Hydrophobia. PMID- 29010902 TI - Musk: Its Pharmacological Action and Therapeutic Uses. PMID- 29010904 TI - The AEtiology of Carcinoma. PMID- 29010903 TI - The Best Source of Iodine (Organic vs. Inorganic) as Related to Thyroid Disturbances. PMID- 29010905 TI - Spontaneous Separation of an Intussusceptum with Recovery. PMID- 29010906 TI - More about the Population Problem. PMID- 29010907 TI - A Case of Cerebrospinal Meningitis. PMID- 29010908 TI - Habitual Formation of Stone in the Bladder. PMID- 29010909 TI - Current Topics. PMID- 29010910 TI - A Study of Monkey-Malaria, and Its Experimental Transmission to Man. PMID- 29010911 TI - Service Notes. PMID- 29010912 TI - Medical News. PMID- 29010913 TI - Welfare Work and the Population Problem. PMID- 29010915 TI - A Contribution to the Surgery of Fascial Transplantation. PMID- 29010914 TI - A Preliminary Note on the Antirachitic Value of Sun-Irradiated Yeast. PMID- 29010916 TI - Correspondence. PMID- 29010917 TI - Observations on the Composition of Butter Imported into Burma. PMID- 29010919 TI - A Plea for the Use of Suction. PMID- 29010918 TI - An Epidemic of Jaundice in Alipuram Jail, Bellary, from January to July 1931. PMID- 29010921 TI - Pre-Natal Dentition. PMID- 29010920 TI - The Interpretation of Wassermann Results in India: Twelve Years' Experience in Calcutta. PMID- 29010922 TI - Relapse of Active Signs in 'Burnt-Out' Cases of Leprosy. PMID- 29010923 TI - A Case of Syphilis of the Lungs. PMID- 29010924 TI - Alepol in Leprosy. PMID- 29010926 TI - The Report of the Drugs Enquiry Committee. PMID- 29010925 TI - Gynaecology in the Tropics: Post-Graduate Clinical Lecture Notes. PMID- 29010927 TI - A Routine Combined Method of 'Widal Reaction and Clot Culture' for the Diagnosis of Enteric Infections. PMID- 29010928 TI - The Uses of Mustard in Medicine. PMID- 29010930 TI - Medical News. PMID- 29010929 TI - Indian Chenopodium. PMID- 29010931 TI - Current Topics. PMID- 29010932 TI - A Case of Sebaceous Horn. PMID- 29010933 TI - Service Notes. PMID- 29010934 TI - Asphyxia Pallida. PMID- 29010935 TI - A Case of Acute Dilatation of the Stomach. PMID- 29010937 TI - An Unusual Case of Foreign Body in the Air Passages. PMID- 29010936 TI - A Mycetoma-Like Condition of the Foot. PMID- 29010938 TI - A Case of Complete Absence of the Penis. PMID- 29010939 TI - The Protective Value of T. A. B. Inoculation as Indicated by the Agglutinating Power of the Serum. PMID- 29010941 TI - The Nomenclature of Bacteriophage. PMID- 29010940 TI - Notes on a Case of Suppurating Hydatid Cyst of the Abdominal Wall. PMID- 29010942 TI - Current Topics. PMID- 29010943 TI - Notes on Two Unusual Cases of Stones in the Bladder. PMID- 29010944 TI - Medical News. PMID- 29010946 TI - The 'Negative Phase' in Prophylaxis by Inoculation of Vaccines. PMID- 29010945 TI - Plasmochin as a Malarial Gametocide. PMID- 29010947 TI - Milk Injections in Malarial Spleens. PMID- 29010948 TI - Malaria in Mingaladon Cantonment, Burma. PMID- 29010949 TI - A Large Ovarian Cyst. PMID- 29010950 TI - Malaria in Calcutta. PMID- 29010952 TI - Public Health Intelligence of the Health Organisation of the League of Nations. PMID- 29010951 TI - A Case of Strangulated Diaphragmatic Hernia. PMID- 29010954 TI - Service Notes. PMID- 29010953 TI - Notes on Urinary Calculi. PMID- 29010955 TI - A Case of Granuloma Inguinale. PMID- 29010956 TI - Cholera and Cholera-Like Vibriophages. PMID- 29010957 TI - Anthrax Pustule of the Neck. PMID- 29010958 TI - A Case of Congenital Malformation of the Rectum Treated by Colostomy. PMID- 29010959 TI - Chloral Hydrate and Paraldehyde as Drugs of Addiction. PMID- 29010960 TI - An Epidemiological and Experimental Study of Dracontiasis in Chitaldrug District. PMID- 29010961 TI - Erratum: Mercurochrome in Leprosy a Corrigendum. AB - [This corrects the article on p. 124 in vol. 67.]. PMID- 29010962 TI - Quacks versus Qualified. PMID- 29010963 TI - Delayed Birth of the Second Twin. PMID- 29010965 TI - Notes on Cataract in the Punjab. PMID- 29010964 TI - Thymol, Menthol and Camphor from Indian Sources. PMID- 29010966 TI - Current Topics. PMID- 29010968 TI - A Preliminary Report on Bacillus Coli in the Calcutta Filtered Water Supply. PMID- 29010967 TI - An Interesting Case of Fibro-Myxoma of the Epipharynx. PMID- 29010969 TI - Invasion of the Nasal Cavity by a Leech. PMID- 29010971 TI - Cinchona Policy. PMID- 29010970 TI - A Case of Typhus Fever in Rangoon. PMID- 29010972 TI - Medical News. PMID- 29010973 TI - Massive Iron Dosage for Chronic Secondary Anaemias. PMID- 29010974 TI - A Case of Cerebral Malaria. PMID- 29010976 TI - The Vitamine Value of the Food Fats of Bengal: A Preliminary Study. PMID- 29010975 TI - A Case with Entamoeba Histolytica in the Urine. PMID- 29010977 TI - The Significance of the Widal Reaction and Other Laboratory Findings in Typhoid Fever. PMID- 29010978 TI - Service Notes. PMID- 29010979 TI - 'Novasurol' in a Case of Hepatic Dropsy. PMID- 29010980 TI - Renal Colic in Infants. PMID- 29010981 TI - Service Notes. PMID- 29010982 TI - Antisera by the Mouth. PMID- 29010983 TI - A Tuberculosis Scheme. PMID- 29010984 TI - Notes on a Case of Gonorrhoeal Arthritis Treated by Injection of Milk. PMID- 29010985 TI - The Calcium Content of the Common Dietaries in India. PMID- 29010987 TI - Medical News. PMID- 29010986 TI - Isohaemagglutination. PMID- 29010988 TI - A Case of Multiple Unilateral Exostoses. PMID- 29010989 TI - More about the Population Problem. PMID- 29010991 TI - Antagonism in Diseases. PMID- 29010990 TI - Cytological Studies of the Blood and Tissues in Kala-Azar and Associated Conditions: Part II Morphology of the Leucocytes in Supra-Vital Preparations. PMID- 29010992 TI - A Preliminary Note on the Action of the Alkaloid of Moringa Pterygosperma (N. O. Moringae). PMID- 29010993 TI - A Case of Volvulus of the Whole of the Small Intestines. PMID- 29010994 TI - The Passing of a Pioneer. PMID- 29010995 TI - Cytological Studies of the Blood and Tissues in Kala-Azar and Associated Conditions: Part III Large Mononuclear Cells in Human Malaria. PMID- 29010996 TI - Current Topics. PMID- 29010997 TI - Obstetrics in the Tropics: Post-Graduate Lecture Notes. PMID- 29010998 TI - Spinal Anaesthesia. PMID- 29010999 TI - Is Bismuth Safe for Intravenous Use? PMID- 29011001 TI - Diphtheria in a Surgical Wound. PMID- 29011000 TI - 'Mercurochrome-220 Soluble' in Leprosy Work. PMID- 29011002 TI - The Intradermal Method of Injecting Hydnocarpus Preparations in Leprosy. PMID- 29011003 TI - Late Eruption of Wisdom Teeth. PMID- 29011004 TI - Sodium Thiosulphate in Mercurial Poisoning. PMID- 29011005 TI - A Noseless Man. PMID- 29011006 TI - Observations on Malaria in Puri District, Orissa. PMID- 29011007 TI - Fracture of the Carpal Scaphoid -A Radiological Study of Thirty Cases. PMID- 29011008 TI - The Determination of Sex. PMID- 29011009 TI - Congenital Bilateral Absence of the Radius and Thumb. PMID- 29011010 TI - A Case of Ileus. PMID- 29011011 TI - Rheumatism in India. PMID- 29011012 TI - The Use of Mustard in Pneumonia. PMID- 29011013 TI - The Prognostic Value of the Aldehyde Reaction in Kala-Azar. PMID- 29011014 TI - Cytological Studies of the Blood and Tissues in Kala-Azar and Associated Conditions: Part I Supra-Vital Staining Technique. PMID- 29011015 TI - Current Topics. PMID- 29011016 TI - The 'Os Naviculare Pedis'. PMID- 29011017 TI - Erosion of the Skull by an Intracranial Tumour. PMID- 29011018 TI - A Case of Rat-Bite Fever. PMID- 29011020 TI - Medical News. PMID- 29011019 TI - Acriflavine as a Counter-Stain in the Ziehl-Neelsen Method of Staining. PMID- 29011022 TI - The Nurses' Charter. PMID- 29011021 TI - The Dosage of Intravenous Mercurochrome. PMID- 29011023 TI - Service Notes. PMID- 29011024 TI - The Reticulo-Endothelial System and Some Diseases in the Tropics. PMID- 29011025 TI - Disintegrated Foetus Discharged through Abdominal Wall. PMID- 29011026 TI - Alepol in the Treatment of Leprosy. PMID- 29011027 TI - A Preliminary Note on New Types of Cholera 'Phage-Types D & E. PMID- 29011028 TI - Observations on a Plasmodium Infection Which Causes Haemoglobinuria in Certain Species of Monkey. PMID- 29011029 TI - Asphyxia Pallida. PMID- 29011030 TI - The Curative Value of a Locally-Prepared Sample of Sulphar-Senobenzene Thiosarmine: Part II. PMID- 29011031 TI - Erratum: Primary Bronchogenic Carcinoma. AB - [This corrects the article on p. 553 in vol. 67.]. PMID- 29011033 TI - Medical News. PMID- 29011032 TI - A Case of Dysphagia Due to Round Worms. PMID- 29011034 TI - Erratum: The Anaemia of Pregnancy: Corrigendum. AB - [This corrects the article on p. 421 in vol. 67.]. PMID- 29011035 TI - A New Conception in the Treatment of Puerperal Sepsis. PMID- 29011036 TI - Service Notes. PMID- 29011037 TI - A Case of Cerebral Malaria. PMID- 29011038 TI - Three Cases of Plague Treated with 'Bayer 205'. PMID- 29011039 TI - Plasmodium Ovale Stephens, 1922. PMID- 29011040 TI - Inversion of the Uterus : A Report of Eight Cases with Comments on Treatment. PMID- 29011041 TI - A Case of Erysipelas. PMID- 29011042 TI - Implantation of the Ureters for Inoperable Vesico-Vaginal Fistula and Ectopia Vesicae : A New Technique. PMID- 29011043 TI - Constants of Pure Buffalo GHI. PMID- 29011044 TI - A Case of Brodie's Abscess. PMID- 29011045 TI - Sulphur Treatment in Mental Diseases: An Experimental Study of 100 Cases. PMID- 29011046 TI - The Influence of Diet on Pregnancy and Early Infant Mortality in India. PMID- 29011048 TI - Treatment and Prophylaxis of Dracontiasis. PMID- 29011047 TI - Epidemic Dropsy Glaucoma. PMID- 29011049 TI - A New Vegetable Culture Medium Made from the Papain Digest of Mung Dal (Phaseolus Mungo), Green Variety. PMID- 29011051 TI - Ronald Ross. PMID- 29011050 TI - Hexylresorcinol as an Anthelmintic. PMID- 29011052 TI - Current Topics. PMID- 29011053 TI - The Defence Mechanism of the Human Body. PMID- 29011054 TI - A Case of Bandicoot-Bite Fever. PMID- 29011055 TI - The Classification and Grading of Different Qualities of Indian Rices in Connection with the Epidemic Dropsy Problem. PMID- 29011056 TI - The AEtiology of Blackwater Fever. PMID- 29011057 TI - Generalised Epilepsy Caused by a Dural Cyst. PMID- 29011058 TI - A Case of Congenital Single Kidney with Dilated Ureter. PMID- 29011059 TI - Notes on a Brief Tour in Malaya. PMID- 29011060 TI - Notes on the Study of Plague in the Field. PMID- 29011061 TI - The Ross Institute. PMID- 29011062 TI - A Fatal Case of Severe Malignant Tertian Malaria. PMID- 29011064 TI - Robert Koch. PMID- 29011063 TI - A Case of Large Pedunculated Lipoma of the Gluteal Region. PMID- 29011065 TI - Dengue Fever in the Rangoon-Mingaladon Area. PMID- 29011066 TI - Changes in Cardiac Rhythm in a Case of Rheumatic Mitral Disease Complicated with Broncho-Pneumonia. PMID- 29011067 TI - The Diagnosis and Treatment of Non-Congestive Glaucoma. PMID- 29011068 TI - The Place of Psychiatry in the Medical Colleges and Schools in India. PMID- 29011069 TI - Current Topics. PMID- 29011071 TI - Medical News. PMID- 29011070 TI - Koch's Discovery of the Tubercle Bacillus-Its Importance and Significance. PMID- 29011072 TI - A Note on Treatment of Liver Abcess by Aspiration. PMID- 29011073 TI - Erratum: Observations on a Plasmodium Infection Which Causes Haemoglobinuria in Certain Species of Monkey. AB - [This corrects the article on p. 246 in vol. 67.]. PMID- 29011074 TI - Erratum: A Study of Monkey-Malaria, and Its Experimental Transmission to Man. AB - [This corrects the article on p. 301 in vol. 67.]. PMID- 29011076 TI - A Study of Induced Malignant Tertian Malaria. PMID- 29011075 TI - A Case of Clinical Malaria with Herpes of the Nose. PMID- 29011077 TI - Service Notes. PMID- 29011078 TI - The Treatment of Bacillary Dysentery by Bacteriophage. PMID- 29011079 TI - The Testing of Anthelminthics. PMID- 29011081 TI - The Provocative Diagnosis of Malaria. PMID- 29011082 TI - Reducing Substances in the Urine: Their Detection and Identification. PMID- 29011080 TI - The Role of Serology in Rabies. PMID- 29011084 TI - A Case of (?) Myxoedema Associated with Exophthalmic Goitre. PMID- 29011083 TI - A Case of Cobra-Bite. PMID- 29011086 TI - The Changing Times. PMID- 29011085 TI - Betel-Chewer's Cancer. PMID- 29011087 TI - A Formula for Intravenous Iodine. PMID- 29011088 TI - Urea-Stibamine. PMID- 29011089 TI - A Note on the Use of Emetine Intravenously. PMID- 29011090 TI - An Entomological Episode of the East African Campaign. PMID- 29011091 TI - Notes on Current Topics. PMID- 29011092 TI - A Preliminary Note on the Pharmacological Action of Some Organic Antimony Derivatives. PMID- 29011093 TI - Quackery in the Mofussil. PMID- 29011094 TI - The Treatment of Malaria with Peracrina 303. PMID- 29011095 TI - A Remarkable Case of Pseudo-Muscular Hypertrophy. PMID- 29011096 TI - A Case of Tuberculous Pneumonia. PMID- 29011098 TI - Service Notes. PMID- 29011097 TI - Cholera and River Waters. PMID- 29011099 TI - The Pathogenic Effects of Helminthic Infections. PMID- 29011100 TI - A Case of Recovery after Bite by a Russell's Viper. PMID- 29011101 TI - Corrigendum. AB - [This corrects the article on p. 1 in vol. 61.]. PMID- 29011102 TI - A Murder Under Insane Hallucination. PMID- 29011103 TI - Medical Relief in Indian Rural Areas. PMID- 29011104 TI - The Treatment of Myelomata by Curettage and Autogenous Cancellous Grafting. PMID- 29011106 TI - Apyrexial Lobar Pneumonia. PMID- 29011105 TI - Ear, Nose and Throat Diseases among Calcutta University Students. PMID- 29011107 TI - A Lesion of the Inferior Rectus: Treatment: Result. PMID- 29011109 TI - A One-Man Apparatus for Intravenous Saline Infusion. PMID- 29011108 TI - The Choice of Quinine Salts for Injection in Malaria. PMID- 29011110 TI - A Case of Bacillary Dysentery. PMID- 29011111 TI - Unusual Symptoms Following the Administration of Urea-Stibamine. PMID- 29011112 TI - A Case of Acute Intestinal Obstruction Caused by Ascaris Lumbricoides. PMID- 29011113 TI - Bombay Millponds and Anopheline Control. PMID- 29011114 TI - Intramuscular Quinine Injections in Malaria. PMID- 29011115 TI - Common-Sense in Advising "A Change of Climate" to Tuberculous Patients. PMID- 29011116 TI - A Study of Cancer in India. PMID- 29011117 TI - Epidemic Dropsy and Secondary Anaemia of Pernicious Type. PMID- 29011118 TI - A Case of Imperforate Hymen. PMID- 29011119 TI - A Note on the Treatment of Puerperal Infection. PMID- 29011120 TI - The Breeding of Anopheles in Sea-Water and at a Short Distance from the Shore. PMID- 29011121 TI - A Case of Amoebic Abscess of the Lung. PMID- 29011122 TI - Notes on Current Topics. PMID- 29011124 TI - Vitamines. PMID- 29011123 TI - The Treatment of Plague: A New Suggestion. PMID- 29011126 TI - Service Notes. PMID- 29011125 TI - Treatment by Prolonged Sleep in Psychiatry. PMID- 29011127 TI - A Case of Diffuse Hypertrophy of the Breasts. PMID- 29011128 TI - Gastro-Enteritis in Alipuram Jail, Bellary. PMID- 29011129 TI - A Case of Cerebral Malaria, Presenting Unusual Features. PMID- 29011130 TI - Intestinal Haemorrhage in a Newly Born Infant. PMID- 29011132 TI - Service Notes. PMID- 29011131 TI - Infantile Cirrhosis of the Liver: Its Causation and Treatment; from a Study of 59 Cases. PMID- 29011133 TI - Observations on Marris's Atropine Test in Enteric Fevers. PMID- 29011134 TI - A Case of Acute Glossitis. PMID- 29011135 TI - Observations on the Treatment of Cholera with Essential Oils, Mistura Pro Diarrhoea and Permanganate of Potash. PMID- 29011136 TI - A Case of Haematuria with Pregnancy in a Retroverted Uterus. PMID- 29011137 TI - A Case of Blackwater Fever Successfully Treated by Injections of Quinine Bihydrochloride and Normal Horse Serum. PMID- 29011138 TI - A Case of Perineal Excision of Ano-Rectal Cancer. PMID- 29011140 TI - Erratum: Some Cases of Asthma. AB - [This corrects the article on p. 287b in vol. 61.]. PMID- 29011139 TI - The Treatment of Plague. PMID- 29011141 TI - On the Use of Mercurosal in Syphilis. PMID- 29011142 TI - The Effect of Prolonged Application of Cold on the Eye. PMID- 29011143 TI - A Case of Wandering Spleen-Splenectomy. PMID- 29011144 TI - Case Histories. PMID- 29011145 TI - Notes on Current Topics. PMID- 29011146 TI - Notes on Cases of Phthisis Treated by Sanocrysin at Lucknow. PMID- 29011147 TI - The Occurrence and Distribution of Yaws in Burma. PMID- 29011148 TI - The Artificial Pneumothorax Treatment of Pulmonary Tuberculosis. PMID- 29011149 TI - Two Cases of Acute Encephalitis Lethargica. PMID- 29011150 TI - The Treatment of Amoebic Abscess of the Liver. PMID- 29011152 TI - Iodeol in Pulmonary Tuberculosis. PMID- 29011151 TI - A Case of Haematuria Relieved after Removal of a Cystic Tumour of the Great Omentum. PMID- 29011153 TI - A Case of Bilateral Dislocation of the Lens. PMID- 29011155 TI - Notes on Current Topics. PMID- 29011154 TI - On a Species of Trichomonas Prevalent in Calcutta. PMID- 29011156 TI - Treatment of Varicose Veins of the Leg by an Occlusion Method. PMID- 29011157 TI - A Case of Sensitiveness to Meat. PMID- 29011158 TI - A Case of Snake-Bite Treated with Antivenomous Serum. PMID- 29011160 TI - A Case of Severe Abdominal Injury. PMID- 29011159 TI - Pulse Diagnosis. PMID- 29011161 TI - An Outbreak of Anthrax Contracted from Handling Infected Beef. PMID- 29011162 TI - An Account of an Outbreak of Cholera at Goalundo Ghat. PMID- 29011163 TI - A Case of Strangulated Hernia. PMID- 29011164 TI - The Provocative Diagnosis of Malaria. PMID- 29011165 TI - Soil Acidity and Survival of Hookworm Larvae. A Reply to Dr. Hirst's Critical Commentary. PMID- 29011166 TI - A Case of Kala-Azar in the Simla Hills. PMID- 29011167 TI - The Occurrence of Urticaria in the Treatment of Malaria by Quinine. PMID- 29011169 TI - The Vagaries of Malaria. The Hepatic Type. PMID- 29011168 TI - A Note on Some Predisposing Factors in Asthma. PMID- 29011170 TI - Thumb Impressions after Death. PMID- 29011172 TI - Cholera in the Punjab in 1925. An Epidemiological Note. PMID- 29011171 TI - Notes on Malaria in the Agency Tracts, Madras Presidency. PMID- 29011173 TI - Medical Education in India. PMID- 29011174 TI - Service Notes. PMID- 29011175 TI - The Gastro-Intestinal Type of Malaria. PMID- 29011177 TI - Erratum: The Ayurvedic Treatment of Rabies. AB - [This corrects the article on p. 591 in vol. 60.]. PMID- 29011176 TI - A Case for Diagnosis. PMID- 29011178 TI - Female Medical Aid in Rural Areas. PMID- 29011179 TI - A Foreign Body in the Pelvis. PMID- 29011180 TI - The Temperature of Rectal and Intravenous Saline Injections in Cholera. PMID- 29011181 TI - Soil Acidity and Survival of Hookworm Larvae. A Critical Commentary. PMID- 29011182 TI - A Case of Hirudiniasis of the Male Urethra. PMID- 29011183 TI - Expulsive Haemorrhage in Cataract Operation in Rural Practice. PMID- 29011184 TI - Two Cases of Synovitis Treated by Intravenous Iodine. PMID- 29011186 TI - A Case of Malignant Tertian Malaria Treated with Intravenous Quinine. PMID- 29011185 TI - Variations in the Potency of Digitalis Preparations in the Tropics (II). PMID- 29011187 TI - The Serological Analysis of Bloodstains in Criminal Cases. (Illustrative Cases). PMID- 29011188 TI - B. Coli Infection in the Puerperim. PMID- 29011189 TI - A Case of Fatal Poisoning by Nitrobenzene. PMID- 29011190 TI - The Darling Prize. PMID- 29011191 TI - The Treatment of Syphilis by Benzo-Bismuth. PMID- 29011192 TI - A Case of Abnormal Salivary Fistula. PMID- 29011193 TI - Service Notes. PMID- 29011194 TI - Back Numbers of the Indian Medical Gazette. PMID- 29011195 TI - Some Observations on the Blood Sugar after Treatment with Insulin in Diabetes. PMID- 29011196 TI - Tuberculosis. PMID- 29011197 TI - Retention of Urine Due to an Imperforate Hymen. PMID- 29011198 TI - The Darling and Lothian Foundations for Research in Malaria. PMID- 29011199 TI - An Unusual Case of Pneumonia in an Infant. PMID- 29011200 TI - Yaws in the Chin Hills. PMID- 29011201 TI - A Case of Foreign Body in the Abdominal Cavity. PMID- 29011202 TI - A Case of Death Due to Bismuth Injection. PMID- 29011203 TI - Some Factors Affecting the Propagation of Hookworm Infections in the Asansol Mining Settlement, with Special Reference to the Part Played by Cockroaches in Mines. PMID- 29011204 TI - A Case of Syphilis of the Liver Suggesting Liver Abscess. PMID- 29011206 TI - A Case of the Meningocele Type of Spina Bifida. PMID- 29011205 TI - A Case of Accidental Abdominal Injury. PMID- 29011207 TI - The General Practitioner and Medical Research. PMID- 29011208 TI - External Medication in Leprosy. PMID- 29011209 TI - Intravenous Iodine in a Case of Abortion Complicated with Septicaemia. PMID- 29011210 TI - An Unusual Case of Nasal Polypus. PMID- 29011211 TI - Glycosuria in Leprosy. PMID- 29011212 TI - Notes on Current Topics. PMID- 29011213 TI - The Diagnosis of Typhoid-Like Fevers with Special Reference to Typhoid and Kala Azar. PMID- 29011215 TI - Malaria and Neurosyphilis. PMID- 29011214 TI - Notes on the Treatment of Benign Tertian Malaria with Cinchona Febrifuge. PMID- 29011216 TI - A Few Interesting Cases at the West Hospital, Rajkot. PMID- 29011217 TI - Anti-Malarial Operations on the Eastern Bengal. Railway-Khulna Branch. PMID- 29011218 TI - The Sixth Congress of the Far Eastern Association of Tropical Medicine. PMID- 29011219 TI - An Atypical Case of Double Hydrocele. PMID- 29011221 TI - Service Notes. PMID- 29011220 TI - A Case of Spontaneous Expulsion of a Foreign Body from the Left Bronchus. PMID- 29011223 TI - Tuberculosis in Bengal. PMID- 29011222 TI - The Use of Eserine in Eye Cases: A Warning. PMID- 29011224 TI - "Bilivaccin-Cholera" versus Commercial Cholera Vaccine. PMID- 29011225 TI - Potassium Permanganate Crystals in Snake-Bite. PMID- 29011226 TI - Notes on Current Topics. PMID- 29011227 TI - A Trial of Oral Vaccination against Bacillary Dysentery in Indian Jails. PMID- 29011228 TI - A Note on an Epidemic of Food Poisoning in Multan City (Punjab). PMID- 29011229 TI - Separation of the Umbilical Cord. PMID- 29011230 TI - Seven-Day Dengue in Lucknow. PMID- 29011231 TI - Intravenous Iodine in a Case of Puerperal Sepsis. PMID- 29011232 TI - Prickly Heat. PMID- 29011233 TI - New Conceptions in Malaria. PMID- 29011234 TI - A Foreign Body in Rectus Abdominis Muscle. PMID- 29011235 TI - Infantile Cirrhosis of the Liver. PMID- 29011236 TI - A Case of Interstitial Fibroid of the Fundus Uteri Causing Acute Complete Inversion of the Uterus. PMID- 29011237 TI - A Curious Preliminary "Treatment" for Couching for Cataract. PMID- 29011238 TI - Some Ideas Engendered by Recent Work on Malaria. PMID- 29011239 TI - Service Notes. PMID- 29011240 TI - Litholapaxy versus Lithotomy. PMID- 29011241 TI - A Case of Acute Parenchymatous Glossitis. PMID- 29011242 TI - Notes on Current Topics. PMID- 29011243 TI - The Operative Treatment of Fractures: With Notes on Fifty-Six Cases. PMID- 29011244 TI - Some Reflections on the Art of Surgery of the Ancient Hindus. PMID- 29011245 TI - A Case of Infection in an Infant with Giardia (Lamblia) Intestinalis. PMID- 29011246 TI - Three Cases of Bronchial Spirochaetosis. PMID- 29011247 TI - A Case of Compound Fracture of the Humerus Treated by a Simple Method. PMID- 29011248 TI - Non-Diluted Milk for Infants. PMID- 29011249 TI - Leptospirosis. With Special Reference to the Existence of Spirochaetosis Ictero Haemorrhagica, or Weil's Disease, in the Andaman Islands. PMID- 29011250 TI - A Case of Apparent Absence of the Uterus. PMID- 29011251 TI - A Case of Meddlesome Midwifery. PMID- 29011252 TI - Suggestion in General Practice. PMID- 29011253 TI - A Case for Diagnosis. PMID- 29011254 TI - Observations on the Results of Treatment of 100 Cases of Cholera. PMID- 29011255 TI - A Case of Myositis Ossificans. PMID- 29011256 TI - Practical Points in Blood Grouping and the Selection of Donors for Blood Transfusion. PMID- 29011257 TI - Heredity and Mental Diseases. PMID- 29011258 TI - Penile Ornaments. PMID- 29011259 TI - A Case of Pleurisy with Effusion. PMID- 29011261 TI - Notes on Current Topics. PMID- 29011260 TI - Paresis Following Emetine Injections. PMID- 29011262 TI - A Case of Malarial Haemoptysis. PMID- 29011263 TI - A Study of the Results of the Appointment of a Public Health Staff in a Rural Area (Khulna District). PMID- 29011264 TI - Iritis Following Cataract Extraction. PMID- 29011265 TI - A Case of Intestinal Obstruction. PMID- 29011266 TI - Twin Pregnancy in a Bicornuate Uterus. PMID- 29011267 TI - A Case of Facial Erysipelas Successfully Treated by Brilliant Green. PMID- 29011269 TI - Service Notes. PMID- 29011268 TI - A Tumour of the Scrotum and Groin Stimulating an Irreducible Inguinal Hernia. PMID- 29011270 TI - A Case of Hydrocephalic Monster. PMID- 29011272 TI - A Case of Severe Sepsis Accompanying Diabetes. PMID- 29011271 TI - Some Points in Snake-Bite. PMID- 29011274 TI - New Conceptions in Amoebiasis. PMID- 29011273 TI - Enterica. Some Notes on the Value of Marris's Atropine Test in Diagnosis, and of T. A. B. Vaccine in Treatment: A Resume of 151 Cases (1919-26). PMID- 29011275 TI - The Treatment of Bacillary Dysentery by Cresol. PMID- 29011276 TI - Principles in the Testing of a Cure. PMID- 29011277 TI - A Case of Cephalo-Tetanus. PMID- 29011278 TI - A Microtest for Blood Sugar. PMID- 29011280 TI - Erratum: The Indian Medical Year, 1925. A Correction. AB - [This corrects the article on p. 1 in vol. 61.]. PMID- 29011279 TI - Some Cases of Asthma. PMID- 29011281 TI - Infantile Cirrhosis of the Liver. PMID- 29011283 TI - Notes on Current Topics. PMID- 29011282 TI - A Case of Fever Due to the Bacillus Faecalis Alkaligenes. PMID- 29011284 TI - A Study of Supra-Pubic Lithotomy. PMID- 29011285 TI - The "Pallang"; a Dyak Curio. PMID- 29011286 TI - An Interesting Case of Malaria. PMID- 29011287 TI - An Interesting Case of Ectopia Vesicae. PMID- 29011288 TI - A Note on the Treatment of Tetanus. PMID- 29011289 TI - A Case of Anaphylactic Asthma Successfully Treated by Peptone Injections. PMID- 29011290 TI - B. I. P. P. in Septic Wounds. PMID- 29011291 TI - Acute Diarrhoea and Vomiting in Children. Complications and Treatment: A Post Graduate Lecture. PMID- 29011292 TI - Service Notes. PMID- 29011293 TI - Anti-Plague Vaccine. PMID- 29011294 TI - A Case of Empyema of the Antrum of Highmore of Unusual Interest. PMID- 29011295 TI - A Case of Pregnancy Complicated by Fibroma of the Cervix Uteri. PMID- 29011296 TI - A Case of Endemic Funiculitis. PMID- 29011297 TI - Urea-Stibamine. PMID- 29011299 TI - Cholera in the Punjab in 1925. PMID- 29011298 TI - A Case of Severe Anaphylactic Reaction Following Injection of Amino-Stiburea. PMID- 29011300 TI - Medical Aspects of Life Insurance in India, with Special Reference to Calcutta. PMID- 29011301 TI - The Medical Register, Bengal. PMID- 29011302 TI - A Cheap and Waterproof Substitute for Plaster-Of-Paris in Outpost Dispensaries. PMID- 29011303 TI - Types of Mental Disorder. PMID- 29011305 TI - Notes on Current Topics. PMID- 29011304 TI - Effects of Bee Venom. PMID- 29011306 TI - Reactions Following the Administration of the Pentavalent Compounds of Antimony: An Analysis of Cases Reported by Several Correspondents. PMID- 29011308 TI - The Use of Sodium Salicylate by Intravenous and Intramuscular Administration. PMID- 29011307 TI - The Treatment of Burns and Scalds by Sterilized Cocoanut Oil. PMID- 29011309 TI - A Case of Scorpion-Bite. PMID- 29011310 TI - On "Agglutinating" and "Non-Agglutinating" Vibrios Found in the Human Intestine and in Water, and the Relationship between Them. PMID- 29011311 TI - The Treatment of Malaria: A Plea for Isolation. PMID- 29011312 TI - A Case of Fracture of the Calvarium. PMID- 29011313 TI - Cotton Seed Asthma. PMID- 29011314 TI - Quinine-Urea in Malaria. PMID- 29011315 TI - The Results of Bismuth Treatment in Seven Hundred Cases of Syphilis. PMID- 29011317 TI - Service Notes. PMID- 29011316 TI - A Few "Don'ts" in Ophthalmic Work. PMID- 29011318 TI - Sterility: Yesterday and To-Day. PMID- 29011319 TI - The Operative Treatment of Fractures. PMID- 29011321 TI - The Treatment of Leucoderma. PMID- 29011320 TI - A Case of Rupture of the Spleen during an Attack of Malaria. PMID- 29011322 TI - A Case of Enormous Ovarian Cyst. PMID- 29011323 TI - Tropical Typhus. PMID- 29011324 TI - The Action of Emetine. PMID- 29011325 TI - Notes on Current Topics. PMID- 29011326 TI - A Case of Pleural Effusion with Abdominal Symptoms. PMID- 29011328 TI - Back Volumes of the Indian Medical Gazette. PMID- 29011327 TI - A Case of Precocious Sexual Development. PMID- 29011329 TI - Two Interesting Cases. PMID- 29011330 TI - The William Gibson Research Scholarship for Medical Women, Royal Society of Medicine. PMID- 29011331 TI - Retiring. PMID- 29011333 TI - Pyrexia of Uncertain Origin. PMID- 29011332 TI - Operations on Old Men. PMID- 29011334 TI - The Dangers of Dusting Powders. PMID- 29011335 TI - A Case of Extensive Fracture of the Skull with Injury to the Brain, Escape of Brain Matter and Recovery. PMID- 29011336 TI - Wanted Scorpions. PMID- 29011337 TI - A Case of Incipient Heart-Block. PMID- 29011340 TI - A Case Resembling Infantile Cirrhosis of the Liver in Which Recovery Took Place. PMID- 29011339 TI - A Case of Acute Haemorrhagic Pancreatitis. PMID- 29011338 TI - A Fatal Result Associated with Filarial Infection. PMID- 29011341 TI - Erratum: On Blood-Sugar and Sugar Tolerance. AB - [This corrects the article on p. 565 in vol. 60.]. PMID- 29011342 TI - Intravenous Iodine in Pulmonary Disease. PMID- 29011343 TI - A Preliminary Note on Two Cases of Asthma Treated with an Autogenous Vaccine Prepared from a Gram-Negative Bacillus Isolated from the Sputum during the Attack. PMID- 29011345 TI - The Alkaloids of Cinchona. PMID- 29011344 TI - A Case of Myomectomy. PMID- 29011346 TI - Service Notes. PMID- 29011347 TI - A Case of Septic Abortion Complicated by Bacillus Coli Infection. PMID- 29011348 TI - A Note on the Incidence of Neuro-Syphilis among Coloured Races. PMID- 29011349 TI - Cases of Foreign Bodies in the Nose and Ear. PMID- 29011350 TI - The Effect of Posterior Gastro-Jejunostomy on Chronic Duodenal Ulcer. PMID- 29011351 TI - An Unusual Case of Extra-Uterine Gestation. PMID- 29011353 TI - A Note on the Treatment of Amoebic Abscess of the Liver. PMID- 29011352 TI - Glycosuria in Leprosy. PMID- 29011354 TI - The Treatment of Bubonic Plague with Intravenous Injections of Iodine. PMID- 29011355 TI - A Huge Sebaceous Cyst of the Scalp. PMID- 29011356 TI - A New Method of Isolating and Cultivating Vibrios from Faeces, Especially Suited for the Detection of Vibrio-Carriers in Field Work. PMID- 29011357 TI - The Influence of Food on Moral and Physical Development in British India. PMID- 29011358 TI - The Baby Cinema in Public Health Propaganda. PMID- 29011359 TI - A Case of Madura Foot Treated by Chemotherapy. Apparent Cure. PMID- 29011360 TI - Obstetrics and Gynaecology. A Review of Recent Advances. PMID- 29011361 TI - Katakar Oil Poisoning. PMID- 29011362 TI - A Case of Dermoid Cyst of the Ovary. PMID- 29011363 TI - Gymnema Sylvestre in the Treatment of Diabetes. PMID- 29011364 TI - Congenital Yaws. PMID- 29011365 TI - A Case of Persistent Hiccough Treated Successfully by Injections of Novocaine into the Phrenic Nerve. PMID- 29011366 TI - Iodoform Poisoning. PMID- 29011367 TI - Fitzsimons' Antivenomous Serum. PMID- 29011368 TI - Corrigendum. AB - [This corrects the article on p. 24 in vol. 61.]. PMID- 29011369 TI - A Case of Complete Avulsion of the Scalp. PMID- 29011370 TI - One Season of Anti-Malarial Work at Pasighat. PMID- 29011373 TI - The Treatment of Certain Cases of Intestinal Obstruction with Belladonna. PMID- 29011372 TI - A Case of Cervical Rib Causing Unilateral Brachial Neuritis; Operation with Amelioration of Symptoms. PMID- 29011371 TI - A Case of Snake-Bite Due to Lachesis Cantoris. PMID- 29011374 TI - A Case of Fibro-Cystic Tumour of the Uterus. Hysterectomy. PMID- 29011375 TI - A Case of Embolism of the Spinal Cord. PMID- 29011376 TI - Notes on Current Topics. PMID- 29011377 TI - An Interesting Case of Narcotic Poisoning and Recovery. PMID- 29011378 TI - Antimony and Filariasis. PMID- 29011379 TI - Service Notes. PMID- 29011380 TI - A Case of Night-Blindness Due to Ascaris Lumbricoides Infection. PMID- 29011381 TI - Essential Oils' Cholera Mixture. PMID- 29011382 TI - On the Inefficiency of "Mercurochrome 220" in the Treatment of Malaria. PMID- 29011383 TI - Bombay Millponds and Anopheline Control. PMID- 29011384 TI - Some Impressions of Japan. PMID- 29011385 TI - Supplement. The Indian Medical Year, 1925. PMID- 29011386 TI - The Price of Santonin. PMID- 29011388 TI - A Case of Vesical Calculus with Enlarged Prostate in an Old Man. PMID- 29011387 TI - Differential Diagnosis in the Tropics. PMID- 29011389 TI - The Treatment of Lacerated Wounds within Two Hours. PMID- 29011390 TI - Two Interesting Cases of Liver Abscess. PMID- 29011392 TI - A Cyst of the Medial Meniscus of the Knee. PMID- 29011391 TI - Indian Digitalis. PMID- 29011393 TI - Remarks on the Operability and Operative Technique of Vesicovaginal Fistula. PMID- 29011394 TI - Service Notes. PMID- 29011395 TI - A Critical Examination of the Antimony Tests for Kala-Azar. PMID- 29011396 TI - Report on Some Cases of Fibroids and Uterine Haemorrhages Treated by Radium. PMID- 29011397 TI - Erratum: A Case of Eclipse Blindness. AB - [This corrects the article on p. 638b in vol. 63.]. PMID- 29011398 TI - An Operation for the Radical Cure of Congenital Oblique Inguinal Hernia in Children. PMID- 29011399 TI - A Case of Double Monster. PMID- 29011400 TI - A Note on the Early History of Grant Medical College, Bombay. PMID- 29011401 TI - Notes on Current Topics. PMID- 29011402 TI - Notes from an Ophthalmologist's Leave Diary. PMID- 29011403 TI - Malaria as a Cause of Cataract. PMID- 29011404 TI - The Treatment of Kala-Azar. PMID- 29011405 TI - Two Cases of (?) Tick Fever from Poona. PMID- 29011406 TI - Rat-Bite Fever. PMID- 29011407 TI - A Case of Landry's Paralysis. PMID- 29011408 TI - A Report on the Investigation into the AEtiology and Prevention of Naga Sore in Assam. PMID- 29011409 TI - Sulfarsenol in the Treatment of Syphilis. PMID- 29011411 TI - Calcutta Students' Health. PMID- 29011410 TI - A Case of Transposed Viscera. PMID- 29011412 TI - The Importance of Medico-Legal Evidence. PMID- 29011413 TI - Gastric and Duodenal Ulcer. PMID- 29011414 TI - Notes on Current Topics. PMID- 29011415 TI - A Case of Imperforate Anus. PMID- 29011416 TI - Chorea in Indians. PMID- 29011418 TI - Diathesis. PMID- 29011419 TI - The Use of Sanocrysin in Pulmonary Tuberculosis. PMID- 29011417 TI - Erratum: Quality of Milk of Some Special Breeds of Himalayan Cows. AB - [This corrects the article on p. 555 in vol. 62.]. PMID- 29011420 TI - A Case of Chronic Amoebic Infection, Especially Affecting the Vermiform Appendix. PMID- 29011421 TI - A Case of Lymphatic Leukaemia. PMID- 29011422 TI - The Value of Inoculation in the Prevention of Cholera. PMID- 29011423 TI - A Simplified Method for Estimation of Sugar in the Blood. PMID- 29011424 TI - A Note on Indian Medicine. PMID- 29011425 TI - Medical Education. PMID- 29011426 TI - A Case of Cerebro-Spinal Meningitis with Recovery. PMID- 29011427 TI - Service Notes. PMID- 29011428 TI - Apomorphine Hydrochloride in the Treatment of Persistent Hiccough. PMID- 29011429 TI - A Note on Stability of Solutions of Calcium Hypochlorite Intended for Use in Snake-Bite. PMID- 29011430 TI - A Case of Balantidial Dysentery. PMID- 29011431 TI - Why Are We One-Sided? PMID- 29011432 TI - Studies in Malaria, as It Affects Indian Railways. PMID- 29011433 TI - Obstetrics and Gynaecology in the Days of the Patriarchs. PMID- 29011434 TI - Supra-Pubic Cystotomy in a Case of Enlarged Prostate. PMID- 29011435 TI - An Outbreak of the Epidemic Dropsy Type of Beriberi in Allahabad, 1927. PMID- 29011437 TI - A Note on the Treatment of Cholera. PMID- 29011436 TI - The Wassermann Test in India. PMID- 29011438 TI - Service Notes. PMID- 29011439 TI - A Preliminary Note on the Use of Ephedrine in Leprosy. PMID- 29011440 TI - Sodii Salicylas and Rheumatic Affections. PMID- 29011442 TI - The Treatment of Bronchial Asthma with Saussurea Lappa (Kuth Root). PMID- 29011441 TI - The Seventh Congress of the Far Eastern Association of Tropical Medicine: Held at Calcutta from Dec. 5th to Dec. 10th, 1928. PMID- 29011443 TI - Chloroform Administration and Its Dangers. And the Role of the Epiglottis in Anaesthetic Collapse. PMID- 29011444 TI - The Seventh Congress of the Far Eastern Association of Tropical Medicine. PMID- 29011445 TI - Myiasis in a Leper. PMID- 29011446 TI - A Case of Incised Wound of the Lung. PMID- 29011447 TI - Difficulties in the Diagnosis of Fevers in the Tropics. PMID- 29011449 TI - On Some Clinical Features of Malignant Tertian Malaria. PMID- 29011448 TI - A Note on the Intravenous Use of Urotropine in Influenza and Nephritis. PMID- 29011451 TI - A Change of Editorship. PMID- 29011450 TI - Genital Hypoplasia in Women. PMID- 29011452 TI - The Burma Government Resolution on Indigenous Medicine. PMID- 29011453 TI - A Case of Foreign Body in the Vaginal Mucous Membrane. PMID- 29011454 TI - Supplement to the "Indian Medical Gazette," April, 1928. PMID- 29011455 TI - Notes on Current Topics. PMID- 29011456 TI - Indian Kala-Azar in a Newly-Born Child. PMID- 29011458 TI - The Indian Science Congress (A Note). PMID- 29011457 TI - Surgical Work in a Mofussil Dispensary. PMID- 29011459 TI - Dysphagia as a Complication of Malaria. PMID- 29011460 TI - A Case of Retrograde Strangulated Hernia. PMID- 29011461 TI - A Case of Probable Dermal Leishmaniasis. PMID- 29011462 TI - Persistent Hiccough Associated with Ascaris Infection. PMID- 29011464 TI - Service Notes. PMID- 29011463 TI - Arthritis as a Complication of Small-Pox. PMID- 29011465 TI - Cough in Cataract Operations. PMID- 29011466 TI - A Case of Hydatid Cyst of the Liver. PMID- 29011467 TI - A Case of Osteo-Sarcoma Following Syphilis. PMID- 29011468 TI - A Case of Cerebral Malaria. PMID- 29011470 TI - An Unusual Foreign Body in the Pleural Cavity. PMID- 29011469 TI - Weil's Disease, as Occurring in the Andamans. PMID- 29011471 TI - Plasmoquine. PMID- 29011472 TI - A Case of Submaxillary Calculus. PMID- 29011473 TI - A Case of Sweating Blood. PMID- 29011474 TI - Dysentery in Secunderabad. PMID- 29011475 TI - Conjunctivitis Vernalis or Spring Catarrh of the Conjunctiva. A Study of Seven Cases. PMID- 29011476 TI - A Case of Malignant Malaria. PMID- 29011477 TI - What the State Is Doing to Stem Disease. PMID- 29011478 TI - Notes on Current Topics. PMID- 29011480 TI - Public Health in India. PMID- 29011479 TI - A Case of Unusual Foreign Body in the OEsophagus. PMID- 29011481 TI - Infantile Cirrhosis of the Liver and Rickets. PMID- 29011482 TI - Conjunctival Congestion after Urea-Stibamine Injection. PMID- 29011483 TI - Cases of Malaria in a Family. PMID- 29011484 TI - A Snake-Bite Poster. PMID- 29011485 TI - A Case of Sexual Perversion. PMID- 29011486 TI - A Case for Diagnosis. PMID- 29011487 TI - A Case of Aneurysm of the Common Carotid Artery at an Early Age. PMID- 29011488 TI - Deep Infiltration Anaesthesia of the Orbit in Eye Operations. PMID- 29011489 TI - Notes on Current Topics. PMID- 29011491 TI - Migraine and Suggestion. PMID- 29011490 TI - Railways and Malaria. PMID- 29011492 TI - The Pernicious Anaemia of Pregnancy. PMID- 29011493 TI - A Note on the Intravenous Administration of Sodium Bicarbonate in Blackwater Fever. PMID- 29011494 TI - The Antimony Test in the Early Diagnosis of Kala-Azar. PMID- 29011496 TI - The Advance of Medicine and Medical Education. PMID- 29011495 TI - The Laboratory Consultant. PMID- 29011497 TI - The Seventh Congress of the Far Eastern Association of Tropical Medicine: Held at Calcutta, from December 5th to 10th, 1927. PMID- 29011498 TI - Sodium Cacodylate in the Treatment of Boils. PMID- 29011499 TI - Intravenous Injections of Sodium Salicylate. PMID- 29011500 TI - Tropical Neurasthenia. PMID- 29011501 TI - Anaesthesia of the Splanchnic Area in the Surgery of the Upper Abdomen. PMID- 29011502 TI - A Case of Recovery after Perforation of a Typhoid Ulcer. PMID- 29011504 TI - Tetanus and the Bone-Setter. PMID- 29011503 TI - A Folklore Charm against Bodily Injuries, Hypodermic Insertion of Gold Needles. PMID- 29011505 TI - An Interesting Case of the Lipoma of the Cheek. PMID- 29011506 TI - Corrigendum. AB - [This corrects the article on p. 72 in vol. 63.]. PMID- 29011507 TI - An Intra-Abdominal Operation for Oblique Inguinal Hernia. PMID- 29011509 TI - A Case of Melanotic Carcinoma. PMID- 29011508 TI - Service Notes. PMID- 29011510 TI - A Note on the Value of Rectal Injections of Potassium Permanganate in the Treatment of Pneumonia. PMID- 29011512 TI - A Case of Melancholic Atonia or Psychocoma. PMID- 29011511 TI - Some Laboratory Findings and Their Significance. PMID- 29011513 TI - A Case of Porro's Hysterectomy. PMID- 29011514 TI - Gynaecology and Obstetrics, 1927. A Practical Digest. PMID- 29011515 TI - Eye-Flies. PMID- 29011516 TI - Massage in the Treatment of Venomous Snake-Bites. PMID- 29011517 TI - The Rationale of Malaria Treatment in Syphilis of the Central Nervous System. PMID- 29011518 TI - Economic Significance of Malaria to an Industrial Concern: A Railway. PMID- 29011519 TI - An Outbreak of Epidemic Dropsy in Allahabad in 1927 (February to April). PMID- 29011520 TI - A Discussion on the Possibility of Ascaris Lumbricoides Infection Being Acquired through the Skin. PMID- 29011522 TI - Service Notes. PMID- 29011521 TI - Report on the Investigation of an Outbreak of Epidemic Dropsy in Surada, a Village Ganjam District. PMID- 29011523 TI - Late Manifestations of Syphilis without a History of Primary Sore. PMID- 29011524 TI - Estimation of Chlorine in Bleaching Powder. PMID- 29011525 TI - Sodium Cacodylate in the Treatment of Boils. PMID- 29011526 TI - A Case of Glioma (Embryonal Neurocytoma) of the Brain Simulating Pituitary Tumour. PMID- 29011528 TI - Diphtheria an Ever-Present Danger in India: A Report on A Series of Cases in Bilaspur District, Central Provinces, India. PMID- 29011527 TI - A Preliminary Note on the Decolourisation of a Solution of Methylene Blue When Left in Contact with Kala-Azar Serum. PMID- 29011529 TI - Technique for Leishman's Stain Suitable for "Field" Application. PMID- 29011531 TI - The Etiology of Green Diarrhoea of Infants: The Deficiency Factor. PMID- 29011532 TI - An Epizootic in Squirrels at Kumbakonam. PMID- 29011530 TI - The Successful Treatment of "Vitiligo Diffusa" by Injections of Sodium Cacodylate. PMID- 29011533 TI - Erratum: Vaso-Motor Disturbance after Injection. AB - [This corrects the article on p. 451b in vol. 63.]. PMID- 29011534 TI - Anaesthesia of the Abdomen. PMID- 29011535 TI - Coagulation of the Peritoneal Inflammatory Exudate. PMID- 29011536 TI - Kyphosis after Tetanus. PMID- 29011537 TI - A Case of Haemorrhagic Pleurisy. PMID- 29011539 TI - The Leprosy Problem-A Step Towards Solution. PMID- 29011540 TI - Notes on Current Topics. PMID- 29011538 TI - A Note on Weil's Disease, or Leptospirosis Icterohaemorrhagica. PMID- 29011542 TI - Observations on 8 Cases of Blackwater Fever, Treated with Serums and Alkalies. PMID- 29011541 TI - Vertical Squint of High Degree in Which Binocular Single Vision Was Maintained in Comparative Comfort. PMID- 29011543 TI - Notes on the Use of Certain Preparations in Leprosy. PMID- 29011544 TI - Toxic Symptoms Following Administration of Carbon Tetrachloride. PMID- 29011545 TI - A Case of Intestinal Obstruction Following a Penetrating Wound in the Abdomen. PMID- 29011546 TI - Digitalis with Special Reference to Auricular Fibrillation. PMID- 29011547 TI - Electro-Coagulation (Diathermy) in Malignant Growth of Face. PMID- 29011548 TI - Plasmoquin in the Treatment of Malaria. PMID- 29011550 TI - Typhus-Like Fever. (Colonel Megaw's Tick-Typhus?). PMID- 29011549 TI - The Nutrition of the Lens and Vitreous. PMID- 29011551 TI - Notes on Current Topics. PMID- 29011552 TI - A Simplified Bed-Side Blood-Sugar Method. PMID- 29011553 TI - An Easy Method of Draining Inaccessible Suppurating Cavities. PMID- 29011554 TI - Service Notes. PMID- 29011555 TI - The Diagnostic Value of a Monocytosis. PMID- 29011557 TI - Deaths under Anaesthetics. PMID- 29011556 TI - William Harvey. PMID- 29011558 TI - The Scientific and Economic Importance of Research on Indian Medicinal Plants. PMID- 29011559 TI - A Simplified Technique for Culturing Malarial Parasites Aerobically. PMID- 29011560 TI - A Case of "Eclipse Blindness". PMID- 29011561 TI - Cerebral Symptoms Associated with Filaria. PMID- 29011562 TI - Rodent Ulcer. PMID- 29011563 TI - A Plea for Vaginal Hysterectomy in India: Its Indications and Technique. A Record of 150 Consecutive Cases. PMID- 29011564 TI - The Pentavalent Antimony Compounds in Tropical Medicine. PMID- 29011565 TI - Fungus Infections of the Hands and Feet. PMID- 29011566 TI - A Case of Renal Calculi at the West Hospital, Rajkot. PMID- 29011567 TI - Prostatism. PMID- 29011568 TI - The Liver Treatment of Pernicious Anaemia. PMID- 29011570 TI - Corrigenda. AB - [This corrects the article on p. 282c in vol. 63.]. PMID- 29011569 TI - The Intensive Treatment of Kala-Azar by Neo-Stibosan. PMID- 29011571 TI - The Treatment of Intestinal Amoebiasis: (An Analysis of Results, and a Review of the Literature). PMID- 29011572 TI - An Interesting Case of Malaria. PMID- 29011573 TI - "Emergent Surgery" in Head Injuries. PMID- 29011574 TI - Medical Etiquette. PMID- 29011575 TI - Notes on Current Topics. PMID- 29011576 TI - Mycetoma Infection: An Appeal for Material. PMID- 29011578 TI - Service Notes. PMID- 29011577 TI - Complete Inversion of the Uterus. PMID- 29011579 TI - Further Observations of the Epidemic Dropsy Form of Beriberi. PMID- 29011580 TI - Tracheotomy for Diphtheria in Children. PMID- 29011581 TI - A Case of Acute Yellow Atrophy. PMID- 29011582 TI - A Case of Serious Vaso-Motor Disturbance after an Injection. PMID- 29011583 TI - An Indigenous Treatment for Snake-Bite. PMID- 29011584 TI - A Case of Medico-Legal Interest. PMID- 29011585 TI - Novel Methods of Treatment. PMID- 29011586 TI - Quinine Intolerance. PMID- 29011587 TI - A Foreign Body in the Gluteal Region. PMID- 29011588 TI - A Case of Infantile Scurvy. PMID- 29011590 TI - Notes on Current Topics. PMID- 29011589 TI - Stone-In-The-Bladder. PMID- 29011591 TI - A Second Case of Madura Foot Treated by Chemotherapy with Apparent Cure. PMID- 29011592 TI - Bleeding of the Gums after Quinine Administration. PMID- 29011593 TI - On Ether by the Open Method as the Anaesthetic of Choice in Indian Conditions. PMID- 29011594 TI - Experiments on the Digestibility of Different Kinds of Rice and Rice Preparations. PMID- 29011595 TI - A Case of Auricular Fibrillation after Aspirin. PMID- 29011596 TI - Industrial Medicine. PMID- 29011597 TI - A Case of Congenital Stenosis of the Pylorus Treated by Rammstedt's Operation. PMID- 29011598 TI - The Therapeutic Activity of Liquid Preparations of Ergot on the Calcutta Market. PMID- 29011599 TI - An Interesting Case of Strangulated Hernia. PMID- 29011600 TI - Radiography as a Help to Correct Diagnosis in Traumatic Lesions. PMID- 29011602 TI - Symptoms Simulating Cholera, Possibly Caused by Round-Worm Infections. PMID- 29011601 TI - Rat-Bite Fever as an Indian Disease. PMID- 29011603 TI - Volvulus of the Small Intestine. PMID- 29011604 TI - The Composition of Plasmoquine. PMID- 29011605 TI - Liver Treatment of Pernicious Anaemia. PMID- 29011606 TI - Service Notes. PMID- 29011607 TI - Infestation of the Human Intestine by Corpid Beetles in Bengal. PMID- 29011609 TI - A Simple Apparatus for Facilitating Radiography of the Limbs. PMID- 29011608 TI - Helminthic Fever. PMID- 29011610 TI - Corrigendum. AB - [This corrects the article on p. 249 in vol. 63.]. PMID- 29011611 TI - A Special X-Ray Technique for the Examination of the Body of the Mandible. PMID- 29011612 TI - Delayed Putrefaction after Burial: A Case of Medico-Legal Interest. PMID- 29011613 TI - Osteomalacia: Its Early Recognition, Modern Prevention, and Treatment: (A Three Years' "Follow Up" of 69 Private Cases). PMID- 29011614 TI - A Case of Hysterical Blindness. PMID- 29011615 TI - Fatal Exfoliative Dermatitis as a Complication of Sanocrysin Treatment of Pulmonary Tuberculosis. PMID- 29011616 TI - A New Organic Aromatic Compound of Bismuth Suitable for Intravenous Injection in the Treatment of Framboesia. PMID- 29011617 TI - An Unusual Case of "Strangulated Hernia". PMID- 29011618 TI - Anaesthesia of the Abdomen. PMID- 29011619 TI - Standards for Maclean's Urea Concentration Test in Healthy Indians. PMID- 29011620 TI - Afebrile B. Typhosus Entero-Colitis. PMID- 29011621 TI - Notes on Current Topics. PMID- 29011623 TI - Electro-Cardiology and Some Observations on Indians. PMID- 29011622 TI - A Case of Multiple Arthritis Following Small-Pox. PMID- 29011625 TI - The Bengal Medical (Amendment) Bill, 1928. PMID- 29011624 TI - Electro-Coagulation (Diathermy). PMID- 29011626 TI - Some Observations on the Anti-Malarial Properties of Plasmochin. PMID- 29011627 TI - A Note on the Breeding and Habits of the Eye-Fly, Siphonella Funicola, Meij. PMID- 29011628 TI - A Rare Case of Dermal Leishmanoid. PMID- 29011629 TI - Three Interesting Photographs. PMID- 29011630 TI - Observations on the Antimony (Urea-Stibamine) Test for Kala-Azar. PMID- 29011631 TI - Notes on a Case of "Black Tongue". PMID- 29011632 TI - Floating Spleen: Splenectomy: Recovery. PMID- 29011633 TI - Service Notes. PMID- 29011634 TI - The Use of Intravenous Quinine and Arsenic in Algid Cases of Malaria. PMID- 29011635 TI - Asphyxia Neonatorum. PMID- 29011636 TI - Notes on Current Topics. PMID- 29011637 TI - An Interesting Case of Malaria. PMID- 29011638 TI - An Aberrant Case of Plague. PMID- 29011640 TI - Atresia of the Vagina and Cervix Uteri. PMID- 29011639 TI - A Case of Pelvic Peritonitis Following Puerperal Sepsis Treated by Intravenous Iodine. PMID- 29011641 TI - A Case of Malaria Simulating Confusional Insanity. PMID- 29011642 TI - Some Observations on the Value of Novasurol in Cardiac Dropsy. PMID- 29011643 TI - A Cataract Expression Operation. PMID- 29011644 TI - The Widal Agglutination Reaction in Healthy Persons. PMID- 29011645 TI - A Case of Impacted Foreign Body in the OEsophagus. PMID- 29011646 TI - An Unusual Case of Lobar Pneumonia. PMID- 29011647 TI - Malaria Investigations by the Department of Public Health, Bengal. PMID- 29011648 TI - The Treatment of Psoriasis by Intramuscular Injections of Milk. PMID- 29011649 TI - Service Notes. PMID- 29011650 TI - Why Are We One-Sided? PMID- 29011651 TI - The Population Problem in India. PMID- 29011652 TI - A Bael Fruit in the Vagina. PMID- 29011653 TI - A Case of Congenital Dilatation of the Colon (Hirschsprun's Disease). PMID- 29011655 TI - A Prescription for Intestinal Colic. PMID- 29011654 TI - A Case of Lipomatosis. PMID- 29011656 TI - Two Cases of Carbon Monoxide Poisoning. PMID- 29011658 TI - The Rate of Loss of Hookworm Eggs from Faeces. PMID- 29011657 TI - Tick-Typhus and Other Sporadic Fevers of the Typhus Group. PMID- 29011659 TI - Tuberculosis of the Body and Cervix of the Uterus. PMID- 29011661 TI - The Vitamines. PMID- 29011660 TI - Seventeen Cases of Scarlet Fever. PMID- 29011662 TI - Neosalvarsan Intravenous Injection: Its Effect on the Patient and the Doctor. PMID- 29011663 TI - Ascaris Infection Simulating Bright's Disease. PMID- 29011664 TI - Microcephaly: A Report on "The Shah Daulah's Mice". PMID- 29011665 TI - A Simple Rat-Trap Used by the Shan Villagers of the Northern Shan States, Burma. PMID- 29011666 TI - Compression Fractures of the Spine. PMID- 29011668 TI - A Case of Mycetoma of the Hand and Foot. PMID- 29011667 TI - A Case of Persistent Hiccough Following Strangulated Hernia. PMID- 29011670 TI - Notes on Current Topics. PMID- 29011669 TI - Two Cases of Renal Tumour in Young Children. PMID- 29011671 TI - Stock Solutions of Quinine. PMID- 29011672 TI - Service Notes. PMID- 29011674 TI - The Treatment of Simple Goitre with Sodium Iodide Intravenously. PMID- 29011673 TI - A Case for Diagnosis. PMID- 29011675 TI - Plasmochin as Compared to Quinine in the Treatment of Malaria. PMID- 29011676 TI - Pathological Evidence Bearing on the Incidence of Diseases in Bombay. PMID- 29011677 TI - Hypertonic Saline in Snake-Bite. PMID- 29011678 TI - Urea-Stibol in the Treatment of Kala-Azar. PMID- 29011679 TI - Supplement to the Indian Medical Gazette, 1927. PMID- 29011680 TI - Artificial Pneumothorax Treatment in India. An Analysis of 306 Cases. PMID- 29011681 TI - Medical Relief in Villages. PMID- 29011682 TI - Suggested Use of Urea-Stibamine in Septic Cases. PMID- 29011683 TI - An Unusual Case. PMID- 29011685 TI - Hookworm Infection in India. PMID- 29011684 TI - A Case of Identical Delirium in Repeated Attacks of BlackWater Fever at Long Intervals. PMID- 29011686 TI - The Price of Novarsenobillon. PMID- 29011687 TI - First-Aid in Riots. PMID- 29011688 TI - The Treatment of Cholera by Acid and Cresol. PMID- 29011689 TI - The Treatment of Fracture of the Femur. PMID- 29011690 TI - A Case of Spontaneous Rupture of Enlarged Spleen. PMID- 29011691 TI - The Treatment of Pernicious Anaemia by Liver. PMID- 29011692 TI - Atropine Sulphate in a Case of Strangulated Hernia. PMID- 29011693 TI - Nursing Arrangements in Up-Country Hospitals and Infirmary Wards. PMID- 29011695 TI - Annual Reports. PMID- 29011694 TI - The Chemistry of the Blood of Normal Healthy Indians. PMID- 29011696 TI - The Mofussil Dispensary. PMID- 29011697 TI - The Incubation Period of Measles. PMID- 29011698 TI - Medical News. PMID- 29011699 TI - Nutritive Value of Rice. PMID- 29011700 TI - The AEtiology of Tropical Macrocytic Anaemia. PMID- 29011702 TI - A Sacro-Coccygeal Cyst. PMID- 29011701 TI - On the Intra-Uterine Infection of the Foetus with Leptospira Icterohaemorrhagiae. PMID- 29011703 TI - Current Topics. PMID- 29011704 TI - Mapharside in the Treatment of Syphilis-A Clinical Study. PMID- 29011705 TI - The Pathogenesis of the Commoner Types of Splenomegaly Met with in India. PMID- 29011706 TI - Further Observations on Leptospiral Infections in Calcutta. PMID- 29011707 TI - A Study of Treatment of Tetanus Based on a Review of 38 Cases from the Year 1932 1937. PMID- 29011708 TI - A Medical Tour in Russia. PMID- 29011710 TI - Service Notes. PMID- 29011711 TI - Medical Education and Rural Medical Relief. PMID- 29011709 TI - A Probable Cause of the Difficulty of Treating Chronic Amoebic Infection in This Country. PMID- 29011712 TI - Abstracts from Reports. PMID- 29011713 TI - A New Method for the Determination of Small Quantities of Cocaine in Presence of Novocaine. PMID- 29011715 TI - Chronic Ulcerative Colitis. PMID- 29011714 TI - Clinical Notes on the Treatment of Acute Cardiac Beri-Beri. PMID- 29011716 TI - Marked Wasting and Retardation of Development Resulting from Lack of Essential Amino Acids in the Diet. PMID- 29011717 TI - H & O Agglutinins in Cholera Patients. PMID- 29011720 TI - Abstracts from Reports. PMID- 29011719 TI - Current Topics. PMID- 29011718 TI - The Effect of M. & B. 693 on Pneumonia Treated in Civil Hospital, Mercara. PMID- 29011721 TI - A Macroscopic Method for the Detection of Motility of Bacteria and for the Study of Flagellar Antigen Relationship. PMID- 29011722 TI - Two Interesting Nervous Cases. PMID- 29011723 TI - Treatment of Peritonsillar Abscess: A New Method. PMID- 29011724 TI - An Experiment in Coolie Line Sanitation: Effects on Health. PMID- 29011725 TI - Medical News. PMID- 29011726 TI - The Incidence of Plague in Mawchi Mines and the Advantage of Adopting Early Preventive and Prophylactic Measures. PMID- 29011727 TI - Service Notes. PMID- 29011728 TI - Infant Mortality in India. PMID- 29011729 TI - Evolution of Gold Therapy in Phthisis: Part II. PMID- 29011730 TI - Chronic Snake-Bite. PMID- 29011731 TI - A Case of Aortic Aneurysm. PMID- 29011733 TI - Treatment of a Carbuncle (Non-Diabetic) Patient without Any Surgical Interference. PMID- 29011732 TI - The Intradermal Test as an Index of Vitamin-C Nutrition. PMID- 29011734 TI - A Lacerated Septic Wound of the Tongue Treated with Cod-Liver Oil. PMID- 29011736 TI - Urticaria Following Prontosil Rubrum Tablets. PMID- 29011735 TI - Prontosil in Indian Strains of Malaria. PMID- 29011737 TI - The Source of Streptococcal Infection in Puerperal Fever. PMID- 29011739 TI - The Calcium and Phosphorus Content of Students' Dietaries. PMID- 29011738 TI - Infant Mortality. PMID- 29011740 TI - 'M. & B. 693' (2-Sulphanilylaminopyridine) in Ape Malaria. PMID- 29011741 TI - A Method of Filling Screw-Capped Bottles with Fluids under Sterile Conditions. PMID- 29011742 TI - Current Topics. PMID- 29011743 TI - The Experimental Production of Syndrome of Epidemic Dropsy in Man. PMID- 29011745 TI - Medical News. PMID- 29011744 TI - Chemotherapy of Gonorrhoea and Other Minor Venereal Diseases with Sulphanilamide Compounds-A Clinical Study. PMID- 29011746 TI - The Failure of Sulphanilamide Therapy in the Treatment of Coliform and Gonococcal Infections of the Genito-Urinary Tract. PMID- 29011747 TI - Service Notes. PMID- 29011749 TI - The Anti-Tuberculosis Movement and Social Service. PMID- 29011748 TI - A Study of the Diet of the Bengali Hindus and Their Nutrition. PMID- 29011751 TI - Abstracts from Reports. PMID- 29011750 TI - The Quality of Medicinal Cod-Liver Oil and Its Preparations on the Indian Market. PMID- 29011752 TI - The Comparative Value of Oil of Chenopodium and Tetrachlorethylene as Anthelmintics for Use in Mass Treatment. PMID- 29011754 TI - A Case of Typhus Fever. PMID- 29011755 TI - Investigation into the Natural Breeding Places of the Siphunculina Funicola Fly, in Assam. PMID- 29011753 TI - The Drug Industry in India and Its Difficulties. PMID- 29011756 TI - Eradication of Hymenolepis Nana Infection. PMID- 29011758 TI - Service Notes. PMID- 29011757 TI - Observations on Some Immunological Aspects of Leptospiral Infections: Part I. PMID- 29011760 TI - The Local Provision of Splints and Tackle for Fractures and Joint Infections in India. PMID- 29011759 TI - Our Daily Rice. PMID- 29011761 TI - A Case of Coeliac Disease. PMID- 29011763 TI - Current Topics. PMID- 29011762 TI - An Interesting Case of Chronic Tetanus. PMID- 29011764 TI - Aberrant Pancreatic Tissue in the Alimentary Tract. PMID- 29011766 TI - Medical News. PMID- 29011765 TI - Atypical Amyloid Disease of the Liver. PMID- 29011767 TI - An Investigation of Calcutta Milk Supply for Presence of Tubercle Bacilli. PMID- 29011768 TI - Primary and Secondary Tuberculosis. PMID- 29011769 TI - Chronic Ulcerative Colitis. PMID- 29011770 TI - Abstracts from Reports. PMID- 29011772 TI - A Case of Gunshot Wound of Lung. PMID- 29011771 TI - 'Patent' Medicines, the Public, and the Doctor. PMID- 29011773 TI - A Recurrent Strangulated Hernia Inguinalis Treated by Section of the Spermatic Cord. PMID- 29011774 TI - The Treatment of Otitis Media. PMID- 29011775 TI - A Note upon an Interesting Serological Type of Leptospira in the Andamans. PMID- 29011776 TI - The Heart in Anaemia. PMID- 29011777 TI - The Disposal and Utilization of Horse Dung and Stable Litter by Composting. PMID- 29011778 TI - Protection of Anti-Plague Workers. PMID- 29011779 TI - Poisoning by Bite from Bungarus Caeruleus with Recovery. PMID- 29011780 TI - Cod-Liver Oil Treatment of a Carbuncle and Two Ulcers. PMID- 29011781 TI - Diet and Peptic Ulcer. PMID- 29011783 TI - The Vitamins: Nicotinic Acid and Pellagra. PMID- 29011782 TI - Arthroplasty of the First Interphalangeal Joint of the Middle Finger. PMID- 29011784 TI - A Probable Cause of the Difficulty of Treating Chronic Amoebic Infection in This Country. PMID- 29011785 TI - A Note on the Destruction of Mosquitoes Caught in the Modified Village Mosquito Trap during Monsoon. PMID- 29011786 TI - Prawns as a Possible Vector of V. Cholerae. PMID- 29011787 TI - The Yellow Fever Position. PMID- 29011788 TI - Spontaneous Subarachnoid Haemorrhage. PMID- 29011789 TI - Notes on Cases of Pellagra Encountered in Calcutta. PMID- 29011790 TI - A Case of Alkaptonuria Associated with Ochronosis and Purpuric Rashes. PMID- 29011791 TI - Abstracts from Reports. PMID- 29011792 TI - Service Notes. PMID- 29011793 TI - Hydrophobia from a Mongoose Bite. PMID- 29011794 TI - Anti-Tetanus Serum. PMID- 29011795 TI - Inhibitory Influence of Chronic Amoebiasis on Immunity against Bacterial Infection. PMID- 29011796 TI - Liquor Arsenicalis in the Treatment of Chorea. PMID- 29011797 TI - An Unusual Case of Cut Throat. PMID- 29011798 TI - Observation on the Pathology and Therapy of the So-Called Frontier Sore. PMID- 29011799 TI - A Microsporum New to India. PMID- 29011800 TI - Colsulanyde in Quinsy. PMID- 29011801 TI - Urticaria Following Prontosil Rubrum Tablets. PMID- 29011802 TI - Some Notes on Clinical Heart Disease. PMID- 29011803 TI - Suprapublic Lithotomy. PMID- 29011804 TI - Medical News. PMID- 29011806 TI - Current Topics. PMID- 29011805 TI - A Note on Pellagra with Special Reference to the District of Kangra (Punjab). PMID- 29011807 TI - Pellagra. PMID- 29011809 TI - A Note on Some Cases of Lathyrism in a Punjab Village. PMID- 29011808 TI - An Interesting Case of Ascites. PMID- 29011810 TI - The Use of Dyes in Various Fungal Infections. PMID- 29011811 TI - An Abdominal Tumour Caused by Gnathostoma Spinigerum (Owen, 1836). PMID- 29011812 TI - Malarial Infection in the Placenta and Transmission to the Foetus. PMID- 29011813 TI - Preliminary Tuberculosis Survey of Rural Areas in the Punjab. PMID- 29011814 TI - Snake Bites and Their Treatment in India: Part II the Management of Sequelae and Complications. PMID- 29011815 TI - Coarctation of the Aorta. PMID- 29011816 TI - The Vital Capacity of the Bengalees. PMID- 29011817 TI - Schick Test Amongst a Group of Indians and Anglo-Indians in Calcutta. PMID- 29011818 TI - Thrombo-Angiitis Obliterans: Report of a Case Treated by Lumbar Ganglionectomy. PMID- 29011820 TI - Current Topics. PMID- 29011819 TI - Scarabiasis or the Presence of Beetles in the Intestine. PMID- 29011821 TI - The Use of Blood Tests in Excluding Paternity and Maternity. PMID- 29011822 TI - Diphtheria in an Unusual Location. PMID- 29011823 TI - Tumours of the Upper Jaw and Its Immediate Neighbourhood. PMID- 29011824 TI - Application of Vaughan's Mode of Delivery, Where Forceps Were Definitely Indicated. PMID- 29011825 TI - Medical News. PMID- 29011826 TI - Lathyrism. PMID- 29011827 TI - Abstracts from Report. PMID- 29011828 TI - Service Notes. PMID- 29011829 TI - Treatment of Cholera (A Note on the Results of Treatment by Different Methods). PMID- 29011830 TI - Ionisable Iron in Certain Indian Food-Stuffs and in Students' Dietaries. PMID- 29011831 TI - Pyocoele of the Canal of Nuck. PMID- 29011832 TI - Abstracts from Reports. PMID- 29011833 TI - Injection Method of Treating Enlarged Inguinal Glands in Early Cases of Lymphopathia Venereum (Lymphogranuloma Inguinale). PMID- 29011834 TI - Lecithin and Glucose in the Treatment of the Opium Habit. PMID- 29011835 TI - Some Experiments on the Absorption of Insulin with Special Reference to Absorption through the Nasal Passages. PMID- 29011836 TI - The Treatment of Lobar Pneumonia. PMID- 29011837 TI - Current Topics. PMID- 29011838 TI - A Simple and Inexpensive Method of Intra-Tracheal Anaesthesia. PMID- 29011839 TI - On a Foreign Body Introduced by Gunshot. PMID- 29011840 TI - Posterior Basal Meningitis in a Child. PMID- 29011841 TI - The Treatment of Acute and Chronic Diarrhoea with a Salt-Free Diet. PMID- 29011842 TI - Is It Pellagra? PMID- 29011843 TI - On the Efficacy of the Gonadotropic Hormones in the Treatment of Whooping Cough. PMID- 29011844 TI - A Rare Cause of Sudden Death. PMID- 29011845 TI - Basic Principles of Solarium Treatment. PMID- 29011846 TI - Evolution of Gold Therapy in Phthisis: Part I. PMID- 29011847 TI - A Case of Cerebellar Apoplexy. PMID- 29011848 TI - Vitamin C in Pulmonary Tuberculosis. PMID- 29011849 TI - Some Anomalies in the Morphology of Plasmodium Vivax Occurring in a Newborn Baby. PMID- 29011850 TI - The Treatment of Pneumonia by May and Baker's 693: Report on 50 Cases with Controls. PMID- 29011852 TI - Medical News. PMID- 29011851 TI - Erysipelas in a Child Aged 6 Days Treated Successfully with Prontosil Rubrum (Bayer). PMID- 29011853 TI - Chemotherapy in Pneumonia. PMID- 29011854 TI - Clinical Observations on Pneumonia Occurring in a Tea-Garden in Assam. PMID- 29011855 TI - Public Health-The Foundation of Nation Building. PMID- 29011856 TI - A Simple Means of Preventing Spider-Lick. PMID- 29011857 TI - Amelia. PMID- 29011859 TI - Service Notes. PMID- 29011858 TI - Arrhenoblastoma. PMID- 29011861 TI - Abstracts from Report. PMID- 29011860 TI - Tuberculosis of Lymphatic Glands in the Neck. PMID- 29011862 TI - Bronchiectasis: Its AEtiology, Pathology, Diagnosis, Prognosis and Treatment. PMID- 29011863 TI - Collapse Therapy of Pulmonary Tuberculosis: Report on a Second Series of 205 Thoracoplasty Operations on 94 Patients from the Wanless Tuberculosis Sanatorium, Wanlesswadi, District Satara. PMID- 29011864 TI - Pneumonoconiosis with Special Reference to Silicosis, Anthracosis and Tuberculosis. PMID- 29011865 TI - A Tuberculosis Survey in a South Indian Town. PMID- 29011866 TI - 'Tubercular' and 'Tuberculous'. PMID- 29011867 TI - The Prognostic Importance of Blood Examinations in Pulmonary Tuberculosis. PMID- 29011869 TI - Current Topics. PMID- 29011868 TI - Medical News. PMID- 29011870 TI - The Special Tuberculosis Numbers. PMID- 29011871 TI - Observations on Some Epidemiological Factors of Tuberculosis in South India: As Studied from Cases at the Government Tuberculosis Hospital, Madras. PMID- 29011872 TI - The Planning of Tuberculosis Institutions in India. PMID- 29011873 TI - Complications during Artificial Pneumothorax Therapy. PMID- 29011874 TI - The Tuberculosis of Tropical Countries: Primitive Tuberculosis and the Partially Modified Disease. PMID- 29011876 TI - Service Notes. PMID- 29011875 TI - The Comparative Value of Different Gold Preparations in the Treatment of Pulmonary Tuberculosis. PMID- 29011878 TI - Service Notes. PMID- 29011877 TI - King George Thanksgiving (Antituberculosis) Fund: A Review of the Activities for the Year 1938-39. PMID- 29011879 TI - A Case of Moniliasis with a Secondary Allergic Patch or 'Moniliide'. PMID- 29011880 TI - Five Years of Anti-Malaria Work at Barwadih Railway Settlement. PMID- 29011881 TI - 'Prontosil Album' in Iliac Abscess. PMID- 29011882 TI - Treatment of Lobar Pneumonia with M. & B. 693. PMID- 29011883 TI - Infection with Giardia Lamblia-Its Pathogenicity and Treatment. PMID- 29011884 TI - Difficulties and Dangers in Providing Donors of Blood. PMID- 29011885 TI - Experimental Malaria Infections in Two Races of A. Stephensi. PMID- 29011886 TI - Rat-Bite Fever in Calcutta. PMID- 29011887 TI - Purulent Arthritis Complicating Smallpox. PMID- 29011889 TI - Medical News. PMID- 29011888 TI - Two Cases of P. U. O. in Children. PMID- 29011890 TI - On Certain Cyclical Changes Observed in the Blood Pictures of Cases of Untreated Anaemia Complicating Pregnancy in Tea Estate Coolies. PMID- 29011891 TI - Ionisable Iron in Cows' and Mothers' Milk. PMID- 29011892 TI - Neglected Compound Fracture of the Tibia. PMID- 29011893 TI - Leprosy and Tuberculosis. PMID- 29011894 TI - Asepsis in the Operating Theatre. PMID- 29011895 TI - Current Topics. PMID- 29011896 TI - Anomalies in the Morphology of P. Vivax. PMID- 29011897 TI - The Epidemiology of Cholera. PMID- 29011898 TI - A Case of Gnathostomiasis with Some Interesting Features. PMID- 29011900 TI - Abstracts from Reports. PMID- 29011899 TI - Chordoma. PMID- 29011901 TI - Treatment of Nervous Diseases by Vitamin B1 with Special Reference to Trigeminal Neuralgia: A Report of 7 Cases. PMID- 29011902 TI - An Unusual Case of Subtertian Malaria. PMID- 29011904 TI - Medical News. PMID- 29011903 TI - A Case of Untreated Traumatic Spondylolisthesis of the Third Cervical Vertebra. PMID- 29011905 TI - Further Observations on Protamine Zinc Insulin in Clinical Diabetes. PMID- 29011907 TI - Acute Tonsillitis Treated with Soluseptasine. PMID- 29011906 TI - The Viability of Vibrio Cholerae in Natural Waters. PMID- 29011908 TI - A Simple Technique of Giving Intravenous Quinine with Saline. PMID- 29011909 TI - Intravenous Anaesthesia with Pentothal Sodium. PMID- 29011910 TI - Calcification of Renal Tumours. PMID- 29011911 TI - Cardio-Vascular Syphilis and Cerebral Symptoms. PMID- 29011912 TI - A Preliminary Report on the Medico-Legal Value of the Finding of Blood on Nail Parings. PMID- 29011913 TI - Acute Mediastinal Emphysema with Generalized Emphysema. PMID- 29011914 TI - Suggestion for a New Type of Tube for Bacteriological Cultures. PMID- 29011915 TI - Naphthalene Poisoning. PMID- 29011916 TI - A Clay Truss for Inguinal Hernia. PMID- 29011918 TI - Abstracts from Reports. PMID- 29011917 TI - The Use of the Domestic Fowl for the Preparation of Diagnostic Antisera. PMID- 29011919 TI - Malaria in Chota Nagpur. PMID- 29011920 TI - The Aschheim-Zondek and the Friedman Tests in the Diagnosis of the Life and Death of a Foetus. PMID- 29011921 TI - The AEtiology of Epidemic Dropsy. PMID- 29011923 TI - Katakar Oil Poisoning. PMID- 29011922 TI - An Outbreak of Epidemic Dropsy in a Closed Community. PMID- 29011924 TI - Cerebro-Spinal Fluid Findings in a Case of Meningococcal Meningitis. PMID- 29011926 TI - Service Notes. PMID- 29011925 TI - Yaws in Chatra Subdivision of Hazaribagh District, Chotanagpur. PMID- 29011927 TI - The Quinine Fraud. PMID- 29011928 TI - Current Topics. PMID- 29011929 TI - Willett's Forceps: A Commentary on Their Value in the Treatment of Placenta Praevia, Especially as Applied to Indian Conditions. PMID- 29011930 TI - An Unusual Case of Cutaneous Amoebic Ulceration around the Anus. PMID- 29011931 TI - From Warfare to Welfare: Being an Exposition of the Social Services of the Red Cross in Commemoration of Its 75th Birthday. PMID- 29011932 TI - Treatment of Two Cases of Acute Meningitis (Pneumococcal Infection) by M. & B. 693. PMID- 29011934 TI - Ages of Epiphysial Union at the Elbow and Wrist Joints Amongst Indian Girls. PMID- 29011935 TI - Current Topics. PMID- 29011933 TI - Demands of Medical Fees from Medical Men. PMID- 29011936 TI - What May We Expect from the Subtotal Hysterectomy? PMID- 29011937 TI - Abstracts from Reports. PMID- 29011938 TI - The Titre of Complement in a Sample of Hospital Population in Calcutta. PMID- 29011939 TI - Service Notes. PMID- 29011940 TI - Thrombocytosis and Spleen Extracts. PMID- 29011941 TI - A Home-Made 'Tomoscope'. PMID- 29011942 TI - A Note on Some Cases of Lathyrism in a Punjab Village. PMID- 29011943 TI - Notes on Cases of Phthisis Treated with Parenteral Gold. PMID- 29011944 TI - Correspondence. PMID- 29011945 TI - The Diagnosis of Kala-Azar in Dispensary Practice. PMID- 29011946 TI - Quality of Quinine Preparations in Indian Hospitals and Dispensaries. PMID- 29011947 TI - Treatment of Lobar Pneumonia with M. & B. 693. PMID- 29011948 TI - The Quinine Fraud. PMID- 29011949 TI - The Treatment of Trichuris Infection with Iron. PMID- 29011950 TI - Transplantation of Ureters for Inoperable Vesicovaginal Fistula: A Report of Two Cases. PMID- 29011952 TI - Medical News. PMID- 29011951 TI - Clinical and Prognostic Factors in Typhoid in India. PMID- 29011953 TI - Snake Bites and Their Treatment in India. PMID- 29011954 TI - Observations on Some Immunological Aspects of Leptospiral Infections: Part II. PMID- 29011955 TI - A Note on the Medical Ethnology of Tuberculosis in the Hills and Frontier Tracts of Assam. PMID- 29011956 TI - Lympho-Sarcoma of Ileum. PMID- 29011957 TI - Hydatid Disease of the Lungs: A Case Report. PMID- 29011958 TI - Clinical Observations on Weil's Disease in India. PMID- 29011959 TI - Study of Diet in Two Industrial Areas in Assam, with Special Reference to the Incidence of Anaemia. PMID- 29011961 TI - Bacteriophage in an Experimental Infection in Mice. PMID- 29011960 TI - The Serological Types of Vibrios Isolated from Cholera Patients in Calcutta. PMID- 29011962 TI - Medical News. PMID- 29011963 TI - Neuropoietin Principle in Gastric Secretion: The AEtiology of Central Nervous Symptoms in Pernicious Anaemia. PMID- 29011965 TI - Sternal Puncture in Kala-Azar. PMID- 29011964 TI - Cooley's Erythroblastic Anaemia. PMID- 29011966 TI - Importance of Chemical Tests for Detection of Seminal Stains in Medico-Legal Investigations. PMID- 29011968 TI - Urticaria Following Liver Extract. PMID- 29011969 TI - Abstracts from Reports. PMID- 29011967 TI - The Incidence of Monilias in Human Faeces. PMID- 29011970 TI - Tropical Sprue: A Resume of a Lecture. PMID- 29011971 TI - Lung Abscess. PMID- 29011972 TI - M. & B. 693 in Pneumonia. PMID- 29011973 TI - Serum Intolerance in Families. PMID- 29011974 TI - M. & B. 693 in Indian Strains of Malaria. PMID- 29011975 TI - Consent for Examination. PMID- 29011977 TI - Iron Metabolism. PMID- 29011976 TI - A Cure for Scorpion Stings. PMID- 29011978 TI - Report of the Use of M. & B. 693 in Pneumonia, Pneumococcal Meningitis, and Pneumococcal Empyema, with Reports on Two Cases of Exfoliative Dermatitis and One of Agranulocytosis Due to M. & B. 693. PMID- 29011979 TI - Service Notes. PMID- 29011980 TI - Clinical Observations on Weil's Disease in India. PMID- 29011981 TI - Early Schizophrenia. PMID- 29011982 TI - A Diet Survey in Bombay. PMID- 29011983 TI - Current Topics. PMID- 29011984 TI - Localized Pretibial 'Myxoedema' in Thyrotoxicosis. PMID- 29011986 TI - Service Notes. PMID- 29011987 TI - Resection of the Right Half of the Colon (Hemicolectomy). PMID- 29011985 TI - Sulphapyridine Anuria. PMID- 29011989 TI - Survival after Shipwreck. PMID- 29011988 TI - Clinical Observations on Malaria Cases with Dangerous Cerebral Manifestations. PMID- 29011990 TI - Report on the Occurrence of Naga Sore in Calcutta. PMID- 29011991 TI - Effect of Yeast and Yeast Products on Complement of Guinea-Pig Serum. PMID- 29011992 TI - Incompatibility of Sulphonamides and Quinine. PMID- 29011993 TI - Surgery in an Emergency. PMID- 29011995 TI - Medical News. PMID- 29011994 TI - A Case of Neuromyelitis Optica (Devics' Disease). PMID- 29011996 TI - Some Statistics Regarding Confinements amongst 2,500 Full-Term Primiparae. PMID- 29011997 TI - Inguinal Hernia. (A Record of 104 Cases). PMID- 29011999 TI - Increasing Incidence of Taenia Solium Infection in Calcutta. PMID- 29011998 TI - A Case of Abdomino-Thoracic Injury, Prolapse of Omentum; Primary Suture of Diaphragm and Chest Wall, Recovery. PMID- 29012000 TI - Vitamin C. PMID- 29012002 TI - Current Topics. PMID- 29012001 TI - Post-Mature Pregnancy: A Case Report. PMID- 29012003 TI - Abstracts from Reports. PMID- 29012004 TI - Intestinal Tuberculosis: Its Diagnosis and Significance in the Treatment of Pulmonary Tuberculosis. PMID- 29012005 TI - A Clinical Study of Fifty Cases of Meningo-Vascular Syphilis. PMID- 29012007 TI - Treatment of an Epidemic of Acute Bacillary Dysentery with M&B 693. PMID- 29012006 TI - Novarsenobillon and Mapharside in the Treatment of the Attack of Malaria. PMID- 29012008 TI - A Simple Thick Drop Method of Staining Blood for Malaria. PMID- 29012009 TI - Abstracts from Reports. PMID- 29012010 TI - Preparation of a Vitamin-A-Active Material from Plant Sources. PMID- 29012011 TI - The Problem of Vitamin A Deficiency. PMID- 29012012 TI - Results of a Survey Undertaken in a Rural Area in Bengal in Maternity and Child Welfare. PMID- 29012013 TI - The Action of 2-Chloro-7-Methoxy-5 (delta-Diethyl-Amino-Butyl) Amino-Acridine on Simian Malaria. PMID- 29012014 TI - Still Another Method of Staining Malaria Parasites. PMID- 29012016 TI - Service Notes. PMID- 29012015 TI - The Effect of Quinine and Stilbamidine (M&B 744) on the Reticulo-Endothelial System as Measured by the Congo-Red Index. PMID- 29012017 TI - Organic Arsenicals in the Treatment of Simian Malaria. PMID- 29012018 TI - Rapid Staining of Malarial Parasites by a Water Soluble Stain. PMID- 29012019 TI - Mahwa Yeast from an Alcohol Factory and Its Vitamin Content. PMID- 29012020 TI - Current Topics. PMID- 29012021 TI - Medical News. PMID- 29012022 TI - Erratum: A Clinical Study of Fifty Cases of Meningo-Vascular Syphilis. AB - [This corrects the article on p. 29 in vol. 79.]. PMID- 29012024 TI - On Humero-Scapular Periarthritis. PMID- 29012023 TI - Some Observations on Ectopia Lentis. PMID- 29012025 TI - A Plea for a More Comprehensive Outlook on the Human Body. PMID- 29012026 TI - Giardiasis. PMID- 29012027 TI - A Case of Acute Encephalitis. PMID- 29012028 TI - Treatment and Management of Starving Sick Destitutes. PMID- 29012030 TI - Current Topics. PMID- 29012029 TI - Basal Tuberculosis and Selective Pneumothorax. PMID- 29012031 TI - Medical News. PMID- 29012032 TI - Studies of Ringworm. Part I. Microsporum Audouini Infection in India. PMID- 29012033 TI - Cancer of the Penis in a Child Aged Two Years. PMID- 29012035 TI - The Treatment of Kala-Azar Complicated with Pulmonary Tuberculosis. PMID- 29012034 TI - Observations on a 24-Hour Rat Test (Aschheim-Zondek Modification) for the Diagnosis of Pregnancy. PMID- 29012036 TI - Protein Hydrolysates in Shock and Inanition. PMID- 29012038 TI - Service Notes. PMID- 29012037 TI - Amoebiasis with Special Reference to Common Secondary Manifestations in the Punjab. PMID- 29012039 TI - The Diagnosis of Malaria, and Field's Rapid Method of Staining Parasites in Blood Films. PMID- 29012040 TI - The Treatment of Kala-Azar with Diamidino-Diphenoxy-Pentane (M&B 800). Final Results of Treatment of the First 32 Cases. PMID- 29012041 TI - A Critical Examination of the Date of the First Authentic Record of Cataract Operation. PMID- 29012042 TI - Abstracts from Reports. PMID- 29012043 TI - Typhus Fevers in India. PMID- 29012045 TI - Abstracts from Reports. PMID- 29012044 TI - Concerning the Wassermann Reaction. PMID- 29012046 TI - Typhus in the United Provinces of India. Being a Contribution to the Study of Typhus Fever. PMID- 29012047 TI - Recent Experiences in the Symptomatology and Treatment of Plague. PMID- 29012048 TI - A Case of Syphilitic Melanoderma. PMID- 29012049 TI - Indian Degrees for Indian Graduates. PMID- 29012051 TI - The Occurrence of Naga Sore in Benares. PMID- 29012050 TI - Protein Hydrolysates in the Treatment of Inanition. PMID- 29012052 TI - Complement-Fixation Tests Performed by N. H. Topping, U.S. Public Health Service, and Other Observations in 'Mysore Typhus'. PMID- 29012053 TI - Treatment of Naga Sore. PMID- 29012054 TI - Typhus in Akola (Berar). PMID- 29012055 TI - A Method of Rapid Staining of Intestinal Flagellates. PMID- 29012057 TI - Indian Degrees for Indian Graduates. PMID- 29012056 TI - A Note on Bacterium Alcaligenes Infection. PMID- 29012058 TI - Protein Hydrolysates as Transfusion Material. PMID- 29012060 TI - Current Topics. PMID- 29012059 TI - The Occurrence of Mites (Acarina) in Human Sputum and Their Possible Significance. PMID- 29012061 TI - Service Notes. PMID- 29012063 TI - Non-Suppurative Osteo-Periostitis as a Complication of Ulcers and Skin Infection: A Report on Fourteen Cases. PMID- 29012064 TI - Service Notes. PMID- 29012062 TI - A Report on Thirty Cases of Typhus Fever (Louse Borne). PMID- 29012065 TI - Evaluation of Gruskin's Intradermal Test for Pregnancy. PMID- 29012066 TI - A Case of Cooley's Anaemia. PMID- 29012067 TI - 'Substitutes for Quinine' and Medical Advertising. PMID- 29012069 TI - The Goal before Us, the Magnitude of the Task and the Part in It of the Medical Woman. PMID- 29012068 TI - A Case of Volvulus of the Sigmoid Colon with an Unusual Post-Operative Course. PMID- 29012070 TI - Some Common Misconceptions of Malaria. PMID- 29012072 TI - Current Topics. PMID- 29012071 TI - 'Lipoid Nephrosis' Cured after an Attack of Typhoid Fever. PMID- 29012073 TI - Medical Aspect of Chest Injuries. PMID- 29012074 TI - An Unusual Case of Congenital Heart Disease with 'Mirror-Image' Dextrocardia (Situs Inversus Totalis), Fallot's Tetralogy and First Degree Heart Block. (A Clinico-Electrocardiographic Study). PMID- 29012075 TI - Traumatic Cerebral Hernia. PMID- 29012076 TI - A Simple Arrangement for Transferring Blood and Serum from Capsules into Tubes for Serological Tests without the Use of Pipettes. PMID- 29012077 TI - Severe Anaemia in Pregnancy. PMID- 29012078 TI - Trans-Pleural OEsophagotomy for a Foreign Body. A Case Report. PMID- 29012079 TI - Report of a Case of Cerebral Malaria. PMID- 29012080 TI - Incompatibility of Sulphonamides and Quinine. PMID- 29012081 TI - Prefrontal Leucotomy in Schizophrenia with Report of 25 Cases. PMID- 29012082 TI - The Quality of Indian-Made Synthetic Drugs-I. Examination of P-Carbamido-Phenyl Arsonic Acid (Carbarsone) of Indian Manufacture. PMID- 29012083 TI - Medical News. PMID- 29012084 TI - Pfeiffer Bacillus Meningitis. PMID- 29012085 TI - Berberine in Malaria. A Preliminary Note. PMID- 29012086 TI - Current Topics. PMID- 29012087 TI - Note on the Treatment of Angular Conjunctivitis with Riboflavin. PMID- 29012088 TI - Medical News. PMID- 29012090 TI - Fluorine and Fluorosis. PMID- 29012089 TI - Observations on the Mottling of Teeth in Rats. PMID- 29012091 TI - Erratum: Some Common Misconceptions of Malaria. AB - [This corrects the article on p. 207 in vol. 79.]. PMID- 29012092 TI - Service Notes. PMID- 29012093 TI - A Case of Diaphragmatic Hernia with Many Complications. PMID- 29012094 TI - Some Tropical Medical Problems in Surgical Cases. PMID- 29012095 TI - Naga Sore. PMID- 29012096 TI - Sternal Puncture. PMID- 29012098 TI - Acute Anterior Poliomyelitis in Adults. PMID- 29012097 TI - Echis Carinata Poisoning. PMID- 29012100 TI - Refined Liver Extracts in the Treatment of Nutritional Macrocytic Anaemias. PMID- 29012099 TI - Treatment of Blackwater Fever. PMID- 29012101 TI - Novarsenobillon and Mapharside in the Treatment of the Attack of Malaria. PMID- 29012102 TI - Degree of Accuracy Realized in Malaria Forecasts in the Punjab for the Years 1923 to 1942. PMID- 29012103 TI - Search for a Specific Chemical Test for Blood Stains: A Comparative Study of the Preliminary Chemical Tests for Blood. PMID- 29012104 TI - Influence of Milk Powder on Fluorine Intoxication in Rats. PMID- 29012106 TI - Abstracts from Reports. PMID- 29012105 TI - A Preliminary Note on the Treatment of 21 Cases of Kala-Azar with Sodium Antimony Gluconate. (With Special Reference to Its Suitability for Mass Administration on Tea Estates). PMID- 29012107 TI - Foreign Body in the OEsophagus: Report of Three Cases. PMID- 29012108 TI - Erratum: Notes on the Use of Cotton in Surgery, and on Plaster Technique. AB - [This corrects the article on p. 712 in vol. 77.]. PMID- 29012109 TI - A Case of Acute Cutaneous Glanders in Man. PMID- 29012110 TI - A Case of Continued Fever Due to Salmonella (Bacterium) Enteritidis (Gaertner). PMID- 29012111 TI - Zinc Ionization in Eczema and Superficial Dermatoses. PMID- 29012112 TI - Desirable Minimum Functions and Organization-Principles for Health Activities. PMID- 29012113 TI - Treatment of Local Sore. PMID- 29012115 TI - Service Notes. PMID- 29012114 TI - The Effect of Indian-Made Mepacrine Hydrochloride on Plasmodium Knowlesi. PMID- 29012116 TI - A Case of Congenital Absence of the Penis. PMID- 29012117 TI - The Treatment of Bacillary Dysentery. PMID- 29012118 TI - Breeding of Chrysomyia Megacephala in Closed Septic Tanks. PMID- 29012119 TI - Hepatitis, Sporadic and Epidemic. PMID- 29012120 TI - Preservation of Hookworm Ova in Faeces. PMID- 29012121 TI - Liver Function and Blood Vitamin C in Secondary Syphilis. PMID- 29012123 TI - Medical News. PMID- 29012122 TI - Ascariasis Simulating Acute Abdomen: Two Case Reports. PMID- 29012124 TI - Current Topics. PMID- 29012125 TI - A Case of Benign Neutropenia Treated by Sodium Pentnucleotide. PMID- 29012126 TI - Seasonal Periodicity of Plasmodia of Malaria at Giriulla, Ceylon. PMID- 29012127 TI - Clinical Experiences of Vitamin Deficiencies in Mysore. PMID- 29012128 TI - Chemotherapy in Cerebrospinal Fever: Experience with Sulphathiazole in a Recent Epidemic of the Disease in Osmanabad in H.E.H. the Nizam's Dominions. PMID- 29012129 TI - Bengal Splenomegaly: A Study of 50 Cases with a Discussion of AEtiology. PMID- 29012130 TI - Transmission of Malaria through Transfusion of Blood. PMID- 29012131 TI - Hypovitaminosis. PMID- 29012133 TI - A Case of Chest Injury Exposing Pleural Cavity and Lung. PMID- 29012132 TI - A Case of Mushroom Poisoning. PMID- 29012134 TI - A Case of Chronic Staphylococcal Abscess of the Patella. PMID- 29012135 TI - Current Topics. PMID- 29012136 TI - Service Notes. PMID- 29012137 TI - Strangulated Hernia with an Unusual History and Course. PMID- 29012138 TI - A Case of Aneurysm of the Transverse Part of the Arch of Aorta. PMID- 29012139 TI - Abstracts from Reports. PMID- 29012141 TI - 'Reconstituted Serum' from Bloodstains: Its Value and Its Limitations. PMID- 29012140 TI - Scurvy in Bilaspur State. PMID- 29012142 TI - Sciatica and Its Treatment by Saline Injections Round the Nerve. PMID- 29012143 TI - A Case of Haemothorax. PMID- 29012144 TI - The Natural History of a Large Cystic Tumour of a Long Bone. PMID- 29012145 TI - Anaesthesia in District Hospitals. PMID- 29012147 TI - Medical News. PMID- 29012146 TI - Alkaline Phosphatase in Bone Tumours. PMID- 29012148 TI - The Health of India. PMID- 29012149 TI - Current Topics. PMID- 29012151 TI - Preliminary Observations on the Use of Rauwolfia Serpentina Benth. In the Treatment of Mental Disorders. PMID- 29012150 TI - Service Notes. PMID- 29012152 TI - The Organization of the Calcutta Blood Bank: Donor and Collection Service. PMID- 29012153 TI - A Plea for a More Comprehensive Outlook on the Human Body. PMID- 29012155 TI - Mental Symptoms in Pellagra and Nicotinic Acid Deficiency. PMID- 29012154 TI - War Injuries of the Eye. PMID- 29012156 TI - Hemeralopia. PMID- 29012157 TI - Sulphonamides in Undulant Fever. PMID- 29012158 TI - Sulphapyridine Anuria. PMID- 29012159 TI - Auto-Haemagglutination. PMID- 29012160 TI - Report on Tropical Ulcers. PMID- 29012161 TI - The Present State of Our Knowledge of Soil and Ground Water Pollution. PMID- 29012162 TI - Phenomenon of Auto-Agglutination in Man after Sulphapyridine. PMID- 29012163 TI - Mongoose Bite and Hydrophobia. PMID- 29012164 TI - Anaesthesia in District Hospitals. PMID- 29012165 TI - Medical News. PMID- 29012166 TI - Observations on the Neuropathic Sequel of Diamidino-Stilbene Therapy in Kala Azar. PMID- 29012167 TI - Current Topics. PMID- 29012168 TI - Retention of the Placenta. PMID- 29012169 TI - Vaginitis Due to Entamoeba Histolytica. PMID- 29012170 TI - Service Notes. PMID- 29012171 TI - Regional Ileitis (Crohn's Disease). PMID- 29012173 TI - Abstracts from Reports. PMID- 29012174 TI - The Pathogenesis of Hepatic Cirrhosis. PMID- 29012172 TI - Extra-Uterine Pregnancy with a Full-Term Live Foetus. PMID- 29012176 TI - A Case of Enlarged Thymus Gland. PMID- 29012175 TI - A Preliminary Note on the Preparation of Seitz Filter-Pads in the Laboratory. PMID- 29012177 TI - A Rare Congenital Anomaly Producing a Clinical Syndrome in an Adult. PMID- 29012178 TI - The Danger of Explosion of Ether-Air Mixtures in the Operation Theatre. PMID- 29012179 TI - The Meningiomas of the Lesser Wing of the Sphenoid. PMID- 29012180 TI - Amoebic Dysentery. PMID- 29012181 TI - Serum Shock and Serum Reaction. PMID- 29012182 TI - Pseudo-Tuberculosis of the Lungs with Eosinophilia. PMID- 29012183 TI - Deterioration of Ascaridol in Oil of Chenopodium. PMID- 29012184 TI - The Takata-Ara Test. PMID- 29012185 TI - Medical News. PMID- 29012186 TI - Cancrum Oris and Allied Conditions. PMID- 29012188 TI - An Efficient and Easily Constructed Drip-Regulator for Transfusions. PMID- 29012187 TI - A Case of Datura Poisoning from External Application. PMID- 29012189 TI - Regional Entero-Colitis (Crohn's Disease). PMID- 29012190 TI - Dr. L. Everard Napier. PMID- 29012191 TI - Ovarian Cyst in a Nulliparous Woman. PMID- 29012192 TI - Hemeralopia. PMID- 29012193 TI - Oro-Genital Syndrome in Avitaminosis : Effect of Treatment with B2 (Complex) Vitamins. PMID- 29012194 TI - Cases of Interest Seen at the Radiological Department of the Erskine Hospital, Madura, during 1941 and 1942. PMID- 29012195 TI - Malaria at Chandpur (Bengal). PMID- 29012197 TI - X-Ray Tracing: A Substitute in Film Shortage. PMID- 29012196 TI - Economy in Quinine. PMID- 29012199 TI - Abstracts from Reports. PMID- 29012198 TI - Torticollis and Convulsions Apparently Due to Ascariasis. PMID- 29012200 TI - Haemolytic Anaemia. PMID- 29012202 TI - Medical News. PMID- 29012203 TI - Corrigendum. AB - [This corrects the article on p. 278 in vol. 78.]. PMID- 29012201 TI - Psammoma of the Choroid Plexus in a Case of Pulmonary Tuberculosis. PMID- 29012204 TI - A Complement-Fixation Test for Kala-Azar. PMID- 29012205 TI - Effect of Reduction of Surface Tension on Mosquito Papae. PMID- 29012206 TI - Advertisements. PMID- 29012207 TI - Current Topics. PMID- 29012208 TI - A Few Suggestions for Blood Bank Workers. PMID- 29012209 TI - The Anterior Shoulder in Pregnancy and Labour : Its Practical Utility. PMID- 29012210 TI - First-Aid Posts. PMID- 29012212 TI - A Note on Vitamin B1 and Experimental Peptic Ulcer. PMID- 29012211 TI - Death in War Time. PMID- 29012213 TI - Service Notes. PMID- 29012214 TI - Treatment of Undulant Fever with Sulphanilamide. PMID- 29012215 TI - Public Health Organization: VII. The Public Health Laboratory. PMID- 29012216 TI - The Result of Amputation of a Limb for Filarial Lymphangitis and Elephantiasis. PMID- 29012217 TI - Grading of Quinine Dosage to Body-Weight : Possible Economy. PMID- 29012218 TI - A Case of Vesicular Mole with Live Birth. PMID- 29012219 TI - Reporting a New Form of Rat-Bite Fever or Sodoku in Bombay (The Gummatoid Form). PMID- 29012220 TI - Rupture of the Left Ventricle- Report of Two Cases. PMID- 29012221 TI - Cataract in Untreated Cases of Diabetes Mellitus. PMID- 29012222 TI - Amoebic Dysentery as a Water-Borne Disease. PMID- 29012223 TI - A Study of Tetanus and Its Treatment with Magnesium Sulphate. PMID- 29012224 TI - Syphilis and the Seriological Tests. PMID- 29012225 TI - Abstracts from Reports. PMID- 29012226 TI - Variations in the Radiosensitivity of Cells and Their Therapeutical Significance. PMID- 29012227 TI - Appendicitis: The Influence of Pathology on Symptoms and Treatment. PMID- 29012228 TI - Recovery of Agar from Used Media. PMID- 29012229 TI - Current Topics. PMID- 29012230 TI - A Study on Leptospirosis in Bombay City. PMID- 29012231 TI - Pyrexia Due to Beetle Infection. PMID- 29012232 TI - Death Following Neoarsphenamine Injection. PMID- 29012233 TI - Service Notes. PMID- 29012234 TI - Giardiasis-A Definite Disease. PMID- 29012235 TI - Knowledge of Sex. PMID- 29012236 TI - Medical News. PMID- 29012237 TI - Two Cases of Anthrax Treated with 'M.&B. 693'. PMID- 29012238 TI - Pseudo-Tuberculosis of the Lungs with Eosinophilia: Contribution to Treatment. PMID- 29012239 TI - A Case of Bronchogenic Carcinoma. PMID- 29012240 TI - The Precipitin Test and the Production of Precipitating Sera. PMID- 29012241 TI - A Design for a Plant for Drying Blood Plasma or Serum. PMID- 29012242 TI - Studies on the Action of Different Brands of Atebrin in Human and Simian Malaria. PMID- 29012243 TI - The Search for an Anti-Malarial Drug in the Indigenous Materia Medica: Part II Caesalpinia Bonducella, Fleming. PMID- 29012244 TI - Gas Gangrene. PMID- 29012245 TI - Medical Planning Commission: Draft Interim Report. PMID- 29012247 TI - Abstracts from Reports. PMID- 29012246 TI - An Epidemic of Small-Pox in the Kolar Gold Fields Area. PMID- 29012248 TI - Current Topics. PMID- 29012249 TI - A Plea for a More Comprehensive Outlook on the Human Body. PMID- 29012251 TI - Medical News. PMID- 29012250 TI - A Note on Giardiasis with Steatorrhoea. PMID- 29012252 TI - The Treatment of Taeniasis. PMID- 29012254 TI - Pancreatic Cyst Treated by Primary Anastomosis to the Stomach. PMID- 29012253 TI - Service Notes. PMID- 29012255 TI - A Case of Acute Monocytic Leukaemia. PMID- 29012256 TI - The Socialization of Medicine. PMID- 29012257 TI - Lethal Action of Potassium Permanganate on Vibrios. PMID- 29012258 TI - The Occurrence of Oriental Sore in the Hyderabad State. PMID- 29012260 TI - Treatment of Kala-Azar: The Present Position. PMID- 29012259 TI - Some Possible New Lines of Treatment of Shock. PMID- 29012261 TI - Developmental Anomaly of Sex-Organs: A Case Note. PMID- 29012262 TI - Fractures and Dislocations of the Vertebrae, with a Report on Fifty Consecutive Cases. PMID- 29012263 TI - Peripheral Neuritis. PMID- 29012264 TI - An Unusual Fracture. PMID- 29012266 TI - Parenchymatous Keratitis Following Riboflavin (Vitamin B2) Deficiency. PMID- 29012265 TI - Abstracts from Reports. PMID- 29012267 TI - Service Notes. PMID- 29012268 TI - An Early Case of Pellagra. PMID- 29012269 TI - Some Impressions of Public Health in India. PMID- 29012270 TI - A Study of Invasiveness and Toxicity of Cholera, Para-Cholera and Saprophytic Vibrios in Animals. PMID- 29012272 TI - Current Topics. PMID- 29012271 TI - Recurring Pellagra Syndrome in a Myxoedematous Subject. PMID- 29012273 TI - The Treatment of Kala-Azar with Diamidino-Di-Phenoxy-Pentane. Preliminary Observations on the Treatment of 32 Cases. PMID- 29012274 TI - The Administration of Sulphur through Drugs and Foods in the Course of Sulphonamide Therapy. PMID- 29012276 TI - Influence of Anti-Anaemic Treatment on the Gastric Function in Hookworm Disease. PMID- 29012275 TI - Some Aspects of Tuberculous Infection in Saidapet. PMID- 29012277 TI - Public Health Organization: VI. The Health of the School Child. PMID- 29012279 TI - Coliform-Group Infections of the Urinary Tract: Their Clinical Types and Incidence in Mysore. PMID- 29012278 TI - Lord Lister and the Treatment of War Wounds. PMID- 29012280 TI - A Modified Medium for Isolation of Dysentery, Enteric and Cholera Organisms. PMID- 29012281 TI - Indian-Made Liver Extracts in the Treatment of Macrocytic Anaemia. PMID- 29012282 TI - Treatment of Oriental Sore with Quinacrine. PMID- 29012283 TI - Observations on Oxycephaly in a Family. PMID- 29012284 TI - Peripheral Neuritis. PMID- 29012285 TI - Agranulocytosis in Kala-Azar. PMID- 29012286 TI - Notes on the Control of Kala-Azar on Tea Estates. PMID- 29012287 TI - Import and Supply of Medical Preparations. PMID- 29012288 TI - Toxicology of Young Shoots of Common Bamboos (Bambusa Arundinacea Willd). PMID- 29012289 TI - Malarial Urticaria-Two Case Reports. PMID- 29012290 TI - Blockage of the Inferior Haemorrhoidal Nerve for Operation on Haemorrhoids. PMID- 29012291 TI - Treatment of Naga Sore. PMID- 29012292 TI - Quinine as a Malaria Prophylactic. PMID- 29012293 TI - A Note on Occupational Dermatitis in the Jute Industry. PMID- 29012294 TI - A Rotary Rack for Doing the Weil-Felix Reaction. PMID- 29012295 TI - Acute Monocytic Leukaemia in Indians. PMID- 29012296 TI - Service Notes. PMID- 29012297 TI - Tests with Mepacrine Hydrochloride, B.P. against Plasmodium Relictum. PMID- 29012299 TI - Lung Abscess Associated with Thrombosis of Veins of Neck and Arm. PMID- 29012298 TI - The Role of Hormones in Sex Disorders in the Male. PMID- 29012300 TI - Abstracts from Reports. PMID- 29012301 TI - Medical News. PMID- 29012302 TI - The Role of Vital Layer (or Schmutzdecke) in Slow Sand Bacteriological Purification. PMID- 29012304 TI - Erratum: A Preliminary Note on the Preparation of Seitz Filter Pads in the Laboratory. AB - [This corrects the article on p. 235 in vol. 78.]. PMID- 29012303 TI - Hypersensitivity of the Carotid Sinus : Report of a Case Showing Signs of Congestive Heart Failure. PMID- 29012305 TI - Need of Industrial Medical Organization. PMID- 29012306 TI - The Toxicity of Emetine. PMID- 29012307 TI - A. Stephensi and Malaria in Calcutta. PMID- 29012309 TI - Current Topics. PMID- 29012308 TI - The Clavicular Sign in Congenital Syphilis. PMID- 29012310 TI - Reporting a Unique Respiration Rate of 119 per Minute and a Pulse-Respiration Ratio of 0.96 : 1.0 in a Case of Broncho-Pneumonia. PMID- 29012311 TI - Normal Haemoglobin Values of the Population of Bihar. PMID- 29012312 TI - The Use and Abuse of Liquid Paraffin. PMID- 29012313 TI - On the Cardiac Effects of Emetine. PMID- 29012314 TI - Medical News. PMID- 29012315 TI - Service Notes. PMID- 29012316 TI - Prevalent Types of Cholera Vibrio. PMID- 29012317 TI - The Position of Pulses in a Diet Based Largely on Cereals. PMID- 29012318 TI - Ectopic Gestation. PMID- 29012319 TI - On the Writing of Medical Articles. PMID- 29012320 TI - Madelung's Deformity : Typical and Reverse Type: With a Case Report. PMID- 29012321 TI - Child Welfare Work: The Importance to the Doctor of First-Hand Knowledge of the Child's Environment. PMID- 29012322 TI - Iniencephaly : A Type of Foetal Monstrosity. PMID- 29012323 TI - Medical News. PMID- 29012325 TI - Service Notes. PMID- 29012324 TI - Pleural Effusion in Artificial Pneumothorax : Its Incidence in Cases Treated from the Beginning in an Out-Patient Department. PMID- 29012326 TI - The Tuberculosis Campaign in India : Where Must the Emphasis Be Placed? PMID- 29012327 TI - Intestinal Tuberculosis : Its Diagnosis and Significance in the Treatment of Pulmonary Tuberculosis. PMID- 29012328 TI - Anti-Tuberculosis Work. PMID- 29012329 TI - Tuberculosis Surveys in an Urban and a Rural Area in Bengal. PMID- 29012330 TI - General Hospitals and Pulmonary Tuberculosis. PMID- 29012331 TI - Current Topics. PMID- 29012332 TI - The Technique of Thoracoscopy and Cauterization of Pleural Adhesions. PMID- 29012333 TI - War and Tuberculosis. PMID- 29012334 TI - Stomach-Wash Examinations for Tubercle Bacilli: A Report of 500 Examinations. PMID- 29012335 TI - Pleural Effusion in Pneumothorax Treatment: Statistical Survey. PMID- 29012336 TI - Abstracts from Reports. PMID- 29012337 TI - The Open Case in Relation to the Control of Tuberculosis. PMID- 29012338 TI - A Symptomless Case of Renal Calculus in Both Kidneys. PMID- 29012339 TI - Quinine Sulphate for Intramuscular Injections. PMID- 29012341 TI - The Aldehyde Test. PMID- 29012340 TI - The Treatment of Shock. PMID- 29012342 TI - Erratum: Intestinal Tuberculosis: Its Diagnosis and Significance in the Treatment of Pulmonary Tuberculosis. AB - [This corrects the article on p. 505 in vol. 78.]. PMID- 29012343 TI - A Note on a New Strain of Actinomyces (Actinomyces Mucosus N. Sp. Basu) Obtained by Blood Culture from a Case of Bronchial (?) Actinomycosis with Metastases. PMID- 29012344 TI - Processing of Liquid Serum. PMID- 29012346 TI - Medical News. PMID- 29012345 TI - Eosinophil Lung. PMID- 29012347 TI - Abstracts from Reports. PMID- 29012348 TI - Current Topics. PMID- 29012349 TI - Royal College of Surgeons of England. PMID- 29012351 TI - The Use and Abuse of Liquid Paraffin. PMID- 29012350 TI - Administering Drugs to Rodents by Mouth. PMID- 29012352 TI - Does a Hookworm Toxin Exist? PMID- 29012353 TI - A Case of Pseudo-Tuberculosis of the Lungs with Eosinophilia. PMID- 29012354 TI - A Massive Aneurysm of the Innominate Artery. A Case with Fatal Termination from Slow 'External Rupture'. PMID- 29012355 TI - Some Observations on Brahmachari's Disease (Post-kala-Azar Infection of the Skin with Leishmania Donovani). PMID- 29012356 TI - Service Notes. PMID- 29012357 TI - Concerning the Wassermann Reaction. PMID- 29012358 TI - Acute Aseptic Meningitis. PMID- 29012359 TI - The Isolysins. PMID- 29012360 TI - 'Androphilic' Mosquitoes. PMID- 29012361 TI - Marked Eosinophilia with Lung Infiltration. PMID- 29012363 TI - A Plea for Medical History Exhibitions in India. PMID- 29012362 TI - Parkinsonian Manifestations Arising in a Parsee Family with 'Essential, Primary or Familial Tremor'. PMID- 29012364 TI - A Case of Tropical Eosinophilia? PMID- 29012365 TI - A Study of 'Choleriform' Disease in the Typhoon Area of Contai. PMID- 29012366 TI - Medical History Exhibition. PMID- 29012367 TI - Chemotherapeutic Studies on Plasmodium Infection in Monkeys: No. V. Action of Tebetren. PMID- 29012368 TI - Amibiarson in the Treatment of Chronic Intestinal Amoebiasis. PMID- 29012369 TI - Some Biochemical Observations on Asthma. PMID- 29012371 TI - Current Topics. PMID- 29012372 TI - Medical News. PMID- 29012370 TI - First Treatments in Medicine. PMID- 29012373 TI - Ascaris Infection and the Bore-Hole Latrine. PMID- 29012374 TI - Service Notes. PMID- 29012375 TI - The Passage of Hookworms after Treatment. PMID- 29012376 TI - Abstracts from Reports. PMID- 29012377 TI - Constants of Mustard Oil. PMID- 29012378 TI - The Immunological Problems of the Typhus Fever Group as Raised by a Sporadic Case of Typhus (Vector Unknown) from Hamirpur in the Plains of India with a Note on the History of Tick Typhus in India. PMID- 29012379 TI - A Case of Hysterical Hiccough. PMID- 29012380 TI - Study of the Cholera Vibrio: The Epidemic and Endemic Types of Cholera Vibrios. PMID- 29012381 TI - A Case of Intestinal Obstruction Caused by Extra-Uterine Pregnancy. PMID- 29012382 TI - A Case of Anophthalmos. PMID- 29012383 TI - Congenital Hydronephrosis Due to an Abnormal Attachment of the Renal Fascia (Of Gerota). PMID- 29012384 TI - Tetrachlorethylene and Its Effect on Tapeworm. PMID- 29012385 TI - Medical News. PMID- 29012386 TI - Current Topics. PMID- 29012387 TI - Atebrin Musonate. PMID- 29012388 TI - The Value of Phrenic Exairesis in the Treatment of Pulmonary Tuberculosis. PMID- 29012389 TI - Bernhardt's Syndrome. PMID- 29012390 TI - The Incidence of Pneumococcal Types in Pneumonia in Assam. PMID- 29012391 TI - Habitual Use of Barbituric Acid Derivatives in India. PMID- 29012393 TI - Service Notes. PMID- 29012392 TI - The Reticulo-Endothelial System in Malarial Haemoglobinuria of Monkeys. PMID- 29012394 TI - The Reticulo-Endothelial System in Malarial Haemoglobinuria of Monkeys: Part II The Relation of Spleen to Haemoglobinuria. PMID- 29012395 TI - A Case of Calcinosis. PMID- 29012396 TI - Preliminary Observations on a New Soluble Atebrin Compound. PMID- 29012397 TI - Cure of Filariasis. PMID- 29012399 TI - Abstracts from Reports. PMID- 29012398 TI - A Preliminary Note on the Cultivation of Vaccinia Virus on the Chorio-Allantoic Membrane of Chick Embryo. PMID- 29012401 TI - A Case of Macrodactyly. PMID- 29012400 TI - A Hygienic Method of Composting Refuse with Night-Soil. PMID- 29012402 TI - Tonsillectomy by a Combination of Dissection and Guillotine Operation. PMID- 29012403 TI - Erratum: Drug Addiction in India and Its Treatment. AB - [This corrects the article on p. 121 in vol. 70.]. PMID- 29012404 TI - Calcutta Medical College: 1835-1935. PMID- 29012405 TI - A Note on Yellow Discoloration in Atebrin Therapy. PMID- 29012406 TI - Latent Syphilis and False-Positive Wassermann Reaction in the Tropics. PMID- 29012407 TI - B. Coli Infection Successfully Treated with M.&B. 693. PMID- 29012408 TI - The Preparation of Liquid Serum for Transfusion Purposes. PMID- 29012409 TI - The Treatment of War Injuries of the Eye. PMID- 29012410 TI - A Preliminary Study of the Rideal-Walker Coefficient Values of Certain Indigenous Essential Oils. PMID- 29012412 TI - Trans-Grafting Operation for Trichiasis and Entropion of the Upper Lid. PMID- 29012411 TI - Intercostal Herpes Zoster Treated with Diphtheria Anti-Toxic Serum. PMID- 29012413 TI - Case of Pityriasis Rosea Showing Enlargement of the Supratrochlear Lymphatic Glands. PMID- 29012414 TI - Abstracts from Reports. PMID- 29012415 TI - Clinical Notes on Six Cases of Pneumonia Treated in Tibet at Altitudes Varying from 9,000 to 13,000 Feet, with M.&B. 693. PMID- 29012416 TI - Minor Drug Habits of India. PMID- 29012417 TI - Health Survey of Punjabi Boys: Skeletal System, Lymphatic Organs and Circulation. PMID- 29012420 TI - Trichinelliasis. PMID- 29012419 TI - Medical News. PMID- 29012418 TI - A Study of Registration of Birth and Its Utilization for Public Health Administration in Maternity and Child Welfare. PMID- 29012421 TI - A Record of Trichinella Spiralis (Owen, 1835) in India. PMID- 29012422 TI - The Effect of Stocking Ricefields with Sullage on Anopheline Breeding at Khurda Road. PMID- 29012424 TI - Weil's Disease with Special Reference to Its Diagnosis and Treatment. PMID- 29012423 TI - A New Type of Drip Regulator for Intravenous Transfusion Work. PMID- 29012425 TI - Alcoholic Beverages in India: Part I. PMID- 29012427 TI - Service Notes. PMID- 29012426 TI - AEtiology of Glaucoma, Its Various Methods of Treatment and Their Merits. PMID- 29012429 TI - Health of the Industrial Worker. PMID- 29012428 TI - Pellagra in the United Provinces. PMID- 29012430 TI - Siamese Twins. PMID- 29012431 TI - Sulphonamides in Topical Application. PMID- 29012432 TI - Simmonds' Disease. PMID- 29012433 TI - The Preparation and Uses of Celluloid Splints. PMID- 29012435 TI - Medical News. PMID- 29012434 TI - Service Notes. PMID- 29012436 TI - Notes on Human Lice. PMID- 29012437 TI - Continuous Eructations Treated by Emetine Hydrochloride. PMID- 29012438 TI - Enteric Tympanites Simulating Acute Intestinal Obstruction. PMID- 29012439 TI - A Liver Abscess Bursting into the Peritoneal Cavity with Signs of Intestinal Obstruction. PMID- 29012441 TI - Erratum: Infantile Beri-Beri. AB - [This corrects the article on p. 97 in vol. 77.]. PMID- 29012440 TI - A Malario-Economic Survey in Rural South India. PMID- 29012442 TI - Current Topics. PMID- 29012443 TI - Magnesium Sulphate Powder in the Treatment of Wounds and Ulcers. PMID- 29012444 TI - Persistence of Diarrhoea in Enteric Fever. PMID- 29012445 TI - Suppuration of the Middle Ear Treated with Urea Solution. PMID- 29012446 TI - Blood and Plasma Transfusion. PMID- 29012447 TI - A Case of Mild Hypopituitarism. PMID- 29012448 TI - A Note on Eve's Halometer. PMID- 29012449 TI - Note on 'Tropical Ulcer' in Coorg. PMID- 29012450 TI - The Assessment of Vitamin Nutrition. PMID- 29012451 TI - Abstracts from Reports. PMID- 29012452 TI - Current Topics. PMID- 29012453 TI - Imperforate External Urinary Meatus in a New-Born Child. PMID- 29012454 TI - Mouse Protection Test as a Method of Diagnosis of Weil's Disease-A Contradiction. PMID- 29012455 TI - Surgical Complications of Filariasis. PMID- 29012456 TI - The Potential Danger of Anopheles Leucosphyrus in Assam. PMID- 29012457 TI - A Brief Review of One Hundred and Thirty-Three Consecutive Cases of Quinsy Treated by Immediate Tonsillectomy. PMID- 29012458 TI - Nylon. PMID- 29012459 TI - Pellagra in Bilaspur State. PMID- 29012461 TI - Medical News. PMID- 29012460 TI - A Case of Air Embolism as a Result of Puncturing the Lung. PMID- 29012463 TI - Service Notes. PMID- 29012462 TI - Can the Deterioration of Ergot Extracts Be Prevented in the Tropics? PMID- 29012464 TI - The Pathological Heart Conditions in Hookworm Disease and Their Causes. PMID- 29012465 TI - The Leprosy Problem. PMID- 29012466 TI - Lung Abscess. PMID- 29012467 TI - Treatment of Cholera with Pyrogen-Free Saline. PMID- 29012468 TI - A Simple Method of Counting Hookworm Eggs in Faeces. PMID- 29012470 TI - Congenital Cystic Bronchiectasis. PMID- 29012469 TI - A Strangulated Paraduodenal Hernia. PMID- 29012471 TI - Measurement of Radiant Energy in Light Therapy. PMID- 29012472 TI - The Applications of the Vitamin-C Test for Ovulation in the Diagnosis of Hormonal Disorders. PMID- 29012474 TI - Abstracts from Reports. PMID- 29012473 TI - Alcoholic Beverages in India: Part II. PMID- 29012476 TI - Public Health Organization : I. Introduction. PMID- 29012475 TI - Pellagra in the United Provinces. PMID- 29012477 TI - The Anti-Pellagra Factor. PMID- 29012478 TI - Boils and Carbuncles: Their Treatment by X-Rays. PMID- 29012479 TI - Toxic Effect of Sulphapyridine on the Liver : A Case Report. PMID- 29012480 TI - Abstracts from Reports. PMID- 29012481 TI - Liver Extract and Sulphonamides in Smallpox. PMID- 29012482 TI - Gastric Acidity in Chronic Ulcerative Colitis. PMID- 29012483 TI - Plagiarism. PMID- 29012484 TI - Gangrenous Stomatitis Treated with M&B 693. PMID- 29012485 TI - Uses of Testosterone Propionate: A Review Together with Short Reports on Its Use in Senile Pruritus and Senile Arthritis in Males. PMID- 29012486 TI - A Case of Post Eclampsia. PMID- 29012488 TI - Medical News. PMID- 29012487 TI - Treatment of Chronic Intestinal Amoebiasis: Use and Abuse of Emetine. PMID- 29012489 TI - Infantile Beri-Beri. PMID- 29012490 TI - Minor Drug Habits of India: Part II. PMID- 29012491 TI - The Role of Protozoa in the Activated Sludge Process. PMID- 29012492 TI - A Peculiar Neurological Sequel to Administration of 4: 4'-Diamidino-Diphenyl Ethylene (M.&B. 744). PMID- 29012493 TI - Chemotherapy in Bacillary Dysentery. PMID- 29012494 TI - Service Notes. PMID- 29012495 TI - Current Topics. PMID- 29012496 TI - Health Leagues in Indian Villages. PMID- 29012497 TI - Sulfanilamide in Ascites. Under What Conditions May This Drug Act as a Diuretic? PMID- 29012498 TI - Intussusception Caused by Amoebic Dysentery. PMID- 29012499 TI - Intrapartum Uterine Rupture. PMID- 29012501 TI - Trichlorethylene. PMID- 29012500 TI - Typhus Fever in Burma: With Record of Three Cases. PMID- 29012502 TI - Knowledge of Sex. PMID- 29012503 TI - Alcoholic Beverages in India: Part III. PMID- 29012504 TI - A Case of Giardiasis. PMID- 29012505 TI - A Case of Menstruation through the Umbilicus as Well as per Vaginam. PMID- 29012506 TI - A Plea for Reasonable Atavism in the Treatment of Fractures. PMID- 29012507 TI - Further Experiences on Endemic Typhus in Mysore. PMID- 29012509 TI - Abstracts from Reports. PMID- 29012508 TI - The Treatment of Kala-Azar by Diamidino Stilbene : Analysis of 101 Cases. PMID- 29012510 TI - Amoebiasis Sine Dysentery. PMID- 29012512 TI - A Case of Pulmonary Myiasis? PMID- 29012511 TI - Examination of Cholera Vomit. PMID- 29012513 TI - Service Notes. PMID- 29012514 TI - A Case of Tetanus. PMID- 29012515 TI - The Assessment of Vitamin Nutrition. PMID- 29012517 TI - Current Topics. PMID- 29012516 TI - Chemotherapy in Bacillary Dysentery. PMID- 29012518 TI - Transposition of Heart and Viscera. PMID- 29012519 TI - Determination of the Age in Bengali Girls in Medico-Legal Cases-Some Practical Difficulties. The Role of X-Ray Examinations of Bones. PMID- 29012520 TI - The Diagnosis of Acute Appendicitis. PMID- 29012521 TI - Local Chemotherapy of Wounds. PMID- 29012522 TI - The Health Status of a Bengal Village: All-India Institute of Hygiene and Public Health Students' Survey. PMID- 29012523 TI - Medical News. PMID- 29012524 TI - Prolapse of Rectum Caused by Vesical Calculus. PMID- 29012525 TI - Proteolytic System in Normal and Various Pathological Conditions. PMID- 29012526 TI - Medical News. PMID- 29012527 TI - Tetrachlorethylene as an Anthelmintic for Tapeworm. PMID- 29012528 TI - Tuberculosis of the Heart: Simulating a Neoplasm. PMID- 29012529 TI - Report of a Case and an Analysis of Twenty-Two Cases of BronchoGenic Carcinomata. PMID- 29012530 TI - Bacillary Dysentery and M.&B. 693 (Sulphapyridine). PMID- 29012531 TI - Osteopoikilosis with Disseminated Lenticular Dermatofibrosis: With the Report of a Case. PMID- 29012532 TI - Influence of Anti-Anaemic Treatment on the Gastric Function in Hookworm Disease. PMID- 29012533 TI - In Vivo Action of Some Substances on the Proteolytic System in Blood. PMID- 29012535 TI - New Emergency Commissions for Service in India Only. PMID- 29012534 TI - Meningitis-Six Case Reports. PMID- 29012536 TI - A Carbuncle Treated with Heat and Chemotherapy. PMID- 29012538 TI - Rural Sanitation-A Key to Success. PMID- 29012537 TI - Hepatoma (Primary Liver-Celled Carcinoma). PMID- 29012540 TI - Shock. PMID- 29012539 TI - A Short Note on the Methods of Water-Proofing Calico or Other Cotton Fabrics. PMID- 29012541 TI - Abstracts from Reports. PMID- 29012542 TI - Current Topics. PMID- 29012543 TI - Five-Year Salvage of Carcinoma Cervix Cases Treated by Radical Vaginal Operation. PMID- 29012544 TI - Pneumonitis. PMID- 29012546 TI - Service Notes. PMID- 29012545 TI - Urticaria Due to Malarial Infection. PMID- 29012547 TI - A Note on the Work of Dr. P. L. Simond on the Transmission and Epidemiology of Plague. PMID- 29012549 TI - Annual Public Health Report of the Province of Assam for the Year 1940. PMID- 29012548 TI - Peculiar Serological Behaviour of a Strain of Leptospira Canicola. PMID- 29012550 TI - A Comparative Study of the Capsular Reaction and the Agglutination Test in the Typing of Pneumococcus. PMID- 29012551 TI - An Analysis of 356 Cases of Enteric Fever Treated in the King Edward Memorial Hospital, Secunderabad, Deccan. PMID- 29012552 TI - A Case of Rupture of Uterus Due to Hydrocephalus. PMID- 29012554 TI - Blood Pressure in the Tropics. PMID- 29012553 TI - Physical Efficiency Test of Schneider on Bombay Medical Students: Part I. PMID- 29012555 TI - A Case of Traumatic Appendicitis. PMID- 29012557 TI - Further Observations on the Mottled Enamel in Nagercoil. PMID- 29012558 TI - Observations on Some Immunological Aspects of Leptospira Icterohaemorrhagiae: Part III Development of Active Immunity in Man Following the Injection of Leptospira Vaccine. PMID- 29012556 TI - A Hydatid Cyst of the Spleen. PMID- 29012559 TI - Medical News. PMID- 29012560 TI - A Note on 'S. V. Chest Brace'. PMID- 29012561 TI - A Study of the Normal Blood Pressure in Indians. PMID- 29012562 TI - A Very Large Ovarian Tumour. PMID- 29012563 TI - Erratum: Haematological Technique. AB - [This corrects the article on p. 742 in vol. 76.]. PMID- 29012564 TI - Treatment of Smallpox with an Antigen-Antibody Mixture. PMID- 29012565 TI - Superficial Keratitis Due to Riboflavin Deficiency. PMID- 29012566 TI - Minor Drug Habits of India. PMID- 29012567 TI - Current Topics. PMID- 29012569 TI - Abstracts from Reports. PMID- 29012568 TI - Sterilization of Snake Venom Preparations. PMID- 29012570 TI - Lung Syphilis. PMID- 29012571 TI - Achlorhydria and Anaemia: An Analysis of 79 Cases. PMID- 29012572 TI - A Case of Hymen Imperforata. PMID- 29012573 TI - Pasteurella Pseudotuberculosis 'Swarming Colonies'. PMID- 29012574 TI - Tinea Imbricata in India. PMID- 29012576 TI - Scurvy in the Famine Areas of Hissar District, Punjab. PMID- 29012575 TI - A Case of Acute Haemorrhagic Pancreatitis. PMID- 29012577 TI - A Note on Eucodal Habit in India. PMID- 29012579 TI - The Village Dai and the Rural Health Programme. PMID- 29012578 TI - Causes of Absence in College-Students. PMID- 29012581 TI - Current Topics. PMID- 29012580 TI - Service Notes. PMID- 29012582 TI - Further Experience of the Treatment of Superficial Keratitis with Riboflavin. PMID- 29012583 TI - A Case of Acute Bachillary Dysentery Treated with M.&B. 693. PMID- 29012584 TI - Further Work on Pyrethrum in the Treatment of Pediculosis. PMID- 29012585 TI - A Modified Method of Reticulocyte Count. PMID- 29012586 TI - Enteric Fever in Calcutta. PMID- 29012587 TI - Indiscriminate Drug Therapy: A Plea for War-Time Drug Economy. PMID- 29012588 TI - Leprosy Institutions in India. PMID- 29012589 TI - Pellagra in the United Provinces. PMID- 29012590 TI - Public Health Organization: II. Organization of a Maternal and Child Health Department. PMID- 29012591 TI - Giardiasis-Two Case Reports. PMID- 29012592 TI - Service Notes. PMID- 29012594 TI - Filters and Filtration: With Special Reference to the Filtration of Blood Plasma and Serum for Transfusion Purposes. PMID- 29012593 TI - The Transmission of Kala-Azar. PMID- 29012595 TI - Abstracts from Reports. PMID- 29012596 TI - A Water Emulsion of Pyrethrum Extract for Spray-Killing Adult Mosquitoes. PMID- 29012597 TI - Bacillary Dysentery Treated with M.&.B. 693: A Case Report. PMID- 29012598 TI - A Case of Giardiasis. PMID- 29012599 TI - Medical News. PMID- 29012600 TI - The Gall-Bladder and Its Veins. PMID- 29012601 TI - Cholesterol and Anaemia. PMID- 29012602 TI - Quinacrine in the Eradication of Giardia Lamblia Infection. PMID- 29012603 TI - A Plea for Smaller Dosage of Sulphapyridine in the Treatment of Pneumonia. PMID- 29012604 TI - Heat Exhaustion and Dehydration in the Arabian Desert. PMID- 29012606 TI - Medical News. PMID- 29012605 TI - Suicide: Its Causes and Prevention. PMID- 29012608 TI - Glaucoma and Epidemic Dropsy. PMID- 29012607 TI - On the Mode of Action of Atebrin on Plasmodium Knowlesi-A Preliminary Note. PMID- 29012609 TI - Four Cases of Dust-Sensitive Asthma. PMID- 29012610 TI - The Technique of Tonsil Enucleation. PMID- 29012611 TI - Service Notes. PMID- 29012613 TI - Current Topics. PMID- 29012612 TI - The Incubation Period of Oriental Sore. PMID- 29012614 TI - Abstracts from Reports. PMID- 29012615 TI - Medical Publications in India. PMID- 29012616 TI - The Utility of Antiseptics and Coagulants in Composting Habitation Wastes. PMID- 29012617 TI - Amoebiasis and Appendicitis. PMID- 29012618 TI - The Species Control of Anophe Lines in India. PMID- 29012620 TI - Abstracts from Reports. PMID- 29012619 TI - An Extreme Case of Tissue Absorption Caused by a Naevus. PMID- 29012621 TI - Types of Pulmonary Tuberculosis Found in Different Communities, with Some Observations Made in Northern India. PMID- 29012623 TI - Service Notes. PMID- 29012622 TI - Early Diagnosis and Treatment of Intestinal Tuberculosis. PMID- 29012625 TI - Bilateral Thoracoplasty: Report on 10 Patients Treated in the Wanless Tuberculosis Sanatorium. PMID- 29012624 TI - Control of Tuberculosis in Cities through Organized Health Chawls. PMID- 29012626 TI - Sulphanilamide Packing in the Treatment of Compound Fracture. PMID- 29012627 TI - After-Histories of Tuberculous Patients. PMID- 29012629 TI - Anti-Tuberculosis Work in India. PMID- 29012628 TI - Some Observations Arising from Tuberculosis Work in the Tuberculosis Clinic, Nagpur. PMID- 29012630 TI - An Investigation into the Types of Tubercle Bacilli Causing Extra-Pulmonary Tuberculous Lesions in the Punjab. PMID- 29012631 TI - P. A. Maplestone. PMID- 29012632 TI - A Case of Imperforate Hymen. PMID- 29012633 TI - Extra-Pleural Pneumothorax Pockets with Sinuses. PMID- 29012634 TI - A Note on a Tuberculin Survey in Sialkot Town. PMID- 29012635 TI - Thoracoplasty in the Treatment of Pulmonary Tuberculosis: An Analysis of 150 Cases. PMID- 29012636 TI - Current Topics. PMID- 29012637 TI - Medical News. PMID- 29012638 TI - Thoracoplasty. PMID- 29012640 TI - Service Notes. PMID- 29012639 TI - Behaviour of the Contralateral Lung in Ambulatory Cases under Unilateral Pneumothorax Treatment: A Record of 500 Cases. PMID- 29012641 TI - An Enquiry into an Outbreak of Cholera in Burma with Special Reference to the Value of Preventive Inoculation. PMID- 29012642 TI - Regional Variations of Leprosy with Special Reference to Tuberculoid Leprosy in India. PMID- 29012643 TI - The Clinical Value of Intramuscular Quinine in Fever during the Puerperium in Tropical and Subtropical Countries. PMID- 29012644 TI - An Unusual Case of Suicidal Stabbing. PMID- 29012645 TI - Current Topics. PMID- 29012646 TI - A Case of Paraplegia and Hydrophobia Following a Full Course of Anti-Rabic Treatment. PMID- 29012647 TI - Facial Cellulitis: A Study of 55 Cases; from February 1932 to August 1936. PMID- 29012648 TI - A Tumour in Which Both Sarcomatous and Carcinomatous Characteristics Are Present. PMID- 29012649 TI - Erratum: An Abdominal Pregnancy Developing to Full Term. AB - [This corrects the article on p. 590 in vol. 71.]. PMID- 29012650 TI - Abstracts from Reports. PMID- 29012651 TI - Intramuscular Quinine. PMID- 29012652 TI - Late Reactions after Anti-Cholera Inoculation. PMID- 29012654 TI - Medical News. PMID- 29012653 TI - Drug Addiction in India and Its Treatment. PMID- 29012655 TI - Current Topics. PMID- 29012657 TI - A Case of Spontaneous Dislocation of Hip Joint Following Typhoid Arthritis. PMID- 29012656 TI - The Functions of a Central Maternal and Child Health Department. PMID- 29012658 TI - Constriction of the Ureter. PMID- 29012659 TI - A Case of Mitral Stenosis with Apparent Bundle Branch Block, Short P-R Intervals and Attacks of Paroxysmal Tachycardia: The Wolff, Parkinson and White Syndrome. PMID- 29012660 TI - Section I Conditions in Trengganu. PMID- 29012661 TI - Preventive Paediatrics: An Account of Health Work in Trengganu, Malaya. PMID- 29012662 TI - Spirillum Minus Infection Acquired from an Indian Squirrel (Sciurus SP.). PMID- 29012663 TI - The Role of Methaemoglobin on the Leptomonad Phase of Leishmania Tropica, with Special Reference to Its Reversion into Leishmania Forms in Culture. PMID- 29012664 TI - Retention of Urine in a New-Born. PMID- 29012665 TI - The Role of Bacillus Faecalis Alcaligenes as a Pathogen in Cystitis of Urinary Bladder. PMID- 29012668 TI - Translucent Areas in the Lung Field. PMID- 29012667 TI - Paratyphoid Infections in India. PMID- 29012666 TI - Sulphapyridine in the Treatment of Tetanus. PMID- 29012670 TI - The Kidney in Malaria. PMID- 29012669 TI - Diagnosis and Pathology of Trachoma in India. PMID- 29012671 TI - Abstracts from Reports. PMID- 29012672 TI - A Ten-Day Fever Simulating Typhoid. PMID- 29012673 TI - Quinine Diuresis in Malarial Conditions. PMID- 29012674 TI - Service Notes. PMID- 29012675 TI - Public Health Organization: III. Public Health and Nutrition. PMID- 29012676 TI - Repeated Respiratory Failure in a New-Born Baby. PMID- 29012677 TI - Composting: A Public Health Problem. PMID- 29012678 TI - A Few Unusual Cases of Poisoning. PMID- 29012679 TI - Public Health Organization: IV. Public Health Engineering. PMID- 29012681 TI - Comments on the History of Leprosy. PMID- 29012680 TI - On Pulmo-Circulatory Dysfunction in Lung Tuberculosis. PMID- 29012682 TI - A Case of Tetanus Simulating Acute Abdomen. PMID- 29012683 TI - Service Notes. PMID- 29012684 TI - Treatment of Malaria in the Present Emergency. PMID- 29012686 TI - Abstracts from Reports. PMID- 29012685 TI - Riboflavin and Its Role in Nutrition. PMID- 29012687 TI - On Soluble Sulphanilamide Derivatives: Part I Toxicity and Absorption. PMID- 29012688 TI - Medical News. PMID- 29012689 TI - A Note on Paranitraniline Poisoning. PMID- 29012691 TI - The 'Austerity' Course of Quinine and the Present Shortage of Antimalarial Drugs. PMID- 29012690 TI - A Case of Gas Gangrene. PMID- 29012692 TI - Intravenous Anaesthesia with Special Reference to the Use of the Barbiturates. PMID- 29012693 TI - Note on Economy in the Use of Anti-Malarial Drugs. PMID- 29012694 TI - Circulation in Fibro-Sarcomas. PMID- 29012695 TI - Current Topics. PMID- 29012697 TI - Preventive Paediatrics: An Account of Health Work in Trengganu, Malaya: The Scheme for Health Work. PMID- 29012696 TI - An Investigation into the Incidence and Type of Tuberculous Infection in Cattle at Amritsar with Special Reference to Human Infections. PMID- 29012698 TI - The Control of Anopheles Minimus by 'Shade' and Related Methods. PMID- 29012699 TI - Partial Degeneration of the Optic Nerve Associated with Vitamin Deficiency. PMID- 29012701 TI - Current Topics. PMID- 29012700 TI - Spontaneous Bursting of a Stone in Urethra. PMID- 29012702 TI - Nutrition and Public Health. PMID- 29012703 TI - An Unusual Case of Cancrum Oris. PMID- 29012704 TI - A Case of Ascites Treated by Autoserotherapy. PMID- 29012706 TI - Service Notes. PMID- 29012705 TI - Treatment of Multiple Warts. PMID- 29012707 TI - Two Cases of Caisson Sickness Presenting 'Aphasia' as One of the Chief Symptoms. PMID- 29012709 TI - A Case of Asthma Treated with Oleo-Sanocrysin. PMID- 29012708 TI - Tuberculosis of the Mammary Gland. PMID- 29012710 TI - A Case of Eclampsia in Twin Pregnancy. PMID- 29012711 TI - Difficulties in the Bacteriological Diagnosis of Cholera Vibrios. PMID- 29012712 TI - The Disorders of Digestion: The Commoner Digestive Disorders of Children in India. PMID- 29012713 TI - Correction. AB - [This corrects the article on p. 503 in vol. 70.]. PMID- 29012715 TI - Medical News. PMID- 29012714 TI - Nasal Conditioning. PMID- 29012717 TI - Abstracts from Reports. PMID- 29012716 TI - A Case of Aconite Poisoning Treated by Hypertonic Saline by the Intravenous Route. PMID- 29012718 TI - A Case of Pellagra. PMID- 29012719 TI - Removal of a Large Ovarian Cyst. PMID- 29012720 TI - A Foreign Body in the Hand. PMID- 29012722 TI - A Case of Haematocolpos. PMID- 29012721 TI - The Use of Stramonium for the Rigidity and Drowsiness Following Encephalitis Lethargica. PMID- 29012723 TI - Cysts of the Spleen: Report of a Case. PMID- 29012725 TI - A Case of Malaria with Acute Mania. PMID- 29012724 TI - Service Notes. PMID- 29012726 TI - Medical News. PMID- 29012727 TI - Intra-Uterine Malarial Infection. PMID- 29012728 TI - Current Topics. PMID- 29012730 TI - Abstracts from Reports. PMID- 29012729 TI - Mental Derangement in Malaria Cases Treated by Atebrin-Musonate Injections. PMID- 29012732 TI - Paul Ehrlich and the Salvarsan Silver Jubilee. PMID- 29012731 TI - Some of the Major Complications in the Treatment of Syphilis. PMID- 29012734 TI - Malaria, Atebrin, and Mental Disturbances. PMID- 29012733 TI - Drug Adulteration and Spurious Drugs in India. PMID- 29012735 TI - The Treatment of Lobar Pneumonia with Intravenous Injections of Alcohol. PMID- 29012736 TI - The Etherington-Wilson Technique of Intrathecal Nerve-Root Block. PMID- 29012738 TI - The Scope of an Assam Tea Garden Laboratory. PMID- 29012737 TI - Epidemic Dropsy. PMID- 29012739 TI - Hydatid Cyst in the Broad Ligament. PMID- 29012740 TI - Atebrin Treatment in Malaria. PMID- 29012741 TI - The Combined System of Soil, Water and Ventilation Pipes. PMID- 29012742 TI - Conservative Surgery in Malignant Disease. PMID- 29012743 TI - Cutaneous Manifestations of Epidemic Dropsy: Part II A Histopathological Study. PMID- 29012744 TI - A Note on the Use of Saccharin as a Sweetening Agent from the Point of View of Public Health. PMID- 29012745 TI - Liver Extract in Epidemic Dropsy: A Suggestion. PMID- 29012746 TI - The Incidence of Cerebro-Spinal Fever in the Borstal Institution and Central Jail, Lahore, during 1934, with a Note on the Use of Anti-Meningococcus Prophylactic Vaccine. PMID- 29012747 TI - Abstract from Report. PMID- 29012748 TI - Observations on Epidemic Dropsy Cases Admitted into the Tropical Diseases Hospital from 1922 to 1933. PMID- 29012749 TI - Service Notes. PMID- 29012751 TI - Epidemic Dropsy. PMID- 29012750 TI - A Preliminary Report on an Epidemic Dropsy Outbreak in Purulia. PMID- 29012752 TI - On the Estimation of Minute Quantities of Atebrin in the Blood. PMID- 29012753 TI - A Case of Psoas Abscess Treated with Injections of Milk. PMID- 29012754 TI - A Case of Spontaneous Subarachnoid Haemorrhage in an Old Man. PMID- 29012755 TI - Pathology of Epidemic Dropsy. PMID- 29012756 TI - A Short Account of Ten Cases of Eclampsia Treated by Intravenous Injections of Magnesium Sulphate. PMID- 29012757 TI - Medical News. PMID- 29012759 TI - Current Topics. PMID- 29012758 TI - An Intractable Ulcer on the Scalp. PMID- 29012760 TI - Clinical Evidence of Rheumatic Fever in the Punjab. PMID- 29012761 TI - Unusual Identification of Explosive. PMID- 29012762 TI - A Case of Septicaemic Plague Simulating Pernicious Malaria. PMID- 29012763 TI - Cutaneous Manifestations of Epidemic Dropsy: Part I A Clinical Study. PMID- 29012764 TI - A Case of Cysticercosis. PMID- 29012765 TI - Correspondence. PMID- 29012767 TI - The Ocular Complications of Epidemic Dropsy. PMID- 29012766 TI - Intramuscular versus Intravenous Quinine. PMID- 29012769 TI - Cinchona Policy. PMID- 29012768 TI - An Unusual Site for a Hydatid Cyst. PMID- 29012770 TI - Evipan-Sodium. PMID- 29012771 TI - Religion and Disease. PMID- 29012772 TI - A Case of Revealed Accidental Haemorrhage. PMID- 29012773 TI - A Case of Dysentery Caused by Balantidium Coli. PMID- 29012775 TI - Service Notes. PMID- 29012774 TI - The Dyspepsias of Southern India. PMID- 29012776 TI - Hill Malaria. PMID- 29012778 TI - A Clinical Case of Pulmonary Tuberculosis: Complete Recovery Following Pneumothorax Treatment Even in a Case with Cavitation. PMID- 29012777 TI - Treatment of Neuritis with Vaccineurin. PMID- 29012779 TI - Ringworm of the Scalp in India. PMID- 29012780 TI - Nerve and Cord Degeneration Referable to Vitamin-A Deficiency. PMID- 29012781 TI - A Case of Minor Epilepsy (Petit mal) Due to Cerebral Trauma. PMID- 29012782 TI - Medical News. PMID- 29012783 TI - Current Topics. PMID- 29012784 TI - Abstracts from Reports. PMID- 29012786 TI - Some Unusual Acute Abdominal Conditions. PMID- 29012785 TI - Some Observations on Dermal Leishmaniasis. PMID- 29012787 TI - A Case of Infantile Scurvy. PMID- 29012788 TI - A Case of Hydrophobia with the Longest Incubation Period on Record. PMID- 29012789 TI - The Rate of Development of Hookworm Eggs. PMID- 29012790 TI - Teeth at Birth. PMID- 29012791 TI - A Case of Sarcoma of the Thigh. PMID- 29012792 TI - Basal Metabolism of Indians in Health and Disease: Its Clinical Significance. PMID- 29012793 TI - Lumbar Sympathectomy in the Treatment of Circulatory Diseases. PMID- 29012795 TI - The Toxicity of Atebrin. PMID- 29012794 TI - Diphtheritic Conjunctivitis: A Report of Two Cases. PMID- 29012797 TI - Service Notes. PMID- 29012796 TI - Observations on Spinal Novocaine Anaesthesia. PMID- 29012798 TI - A Fatal Case of Bronchial Asthma. PMID- 29012800 TI - A Case of Abscess of the Spleen in Malaria. PMID- 29012799 TI - A Simple Fly Trap. PMID- 29012801 TI - Some Observations on the Toxicity of Synthetic Anti-Malarial Remedies. PMID- 29012802 TI - Atebrin in the Treatment of Malaria in Railway Employees. PMID- 29012803 TI - Medical News. PMID- 29012804 TI - Abstracts from Reports. PMID- 29012806 TI - Delirium after Quinine Administration. PMID- 29012805 TI - A Case of Recurrent Vitreous Haemorrhages. PMID- 29012807 TI - Passive Collapse of Lung Due to Spontaneous Pneumothorax. PMID- 29012808 TI - Treatment of Acute Bacillary Dysentery with Anti-Dysenteric Serum and Bacteriophage. PMID- 29012809 TI - A Large Ovarian Cyst. PMID- 29012810 TI - Familial Periodic Paralysis. PMID- 29012811 TI - Notes on an Experiment on the Prophylactic and Curative Value of Atebrin and Plasmochin Therapy in a Tea Garden in Assam. PMID- 29012812 TI - Entire Absence of the Uterus. PMID- 29012813 TI - The Royal Medico-Psychological Association's Classification of Mental Disorders. PMID- 29012814 TI - Peri-Anal Ulceration Complicating Kala-Azar. PMID- 29012815 TI - Intramuscular versus Intravenous Quinine. PMID- 29012816 TI - A Case of Strangulated Hernia. PMID- 29012817 TI - The Influence of Fresh Bile on Guinea-Worm Larvae Encysted in Cyclops: A Preliminary Report. PMID- 29012818 TI - The Inspectional Value of Phrynoderma and 'Sore Mouth'. PMID- 29012819 TI - A Case of Surgical Emphysema. PMID- 29012820 TI - Current Topics. PMID- 29012821 TI - Thrombo-Angiitis Obliterans. PMID- 29012822 TI - A Simple Method of Bug Destruction. PMID- 29012824 TI - A Case of Severe Bleeding after Tooth Extraction. PMID- 29012823 TI - Clinical Evidence of Rheumatic Fever in the Punjab. PMID- 29012825 TI - Conservative Surgery in Malignant Disease. PMID- 29012826 TI - Intramuscular versus Intravenous Quinine. PMID- 29012827 TI - The Surgery of the Ruptured Spleen. PMID- 29012828 TI - Treatment of Psoriasis. PMID- 29012829 TI - Viper Snake Bite: Treatment and Recovery. PMID- 29012831 TI - Service Notes. PMID- 29012830 TI - A Note on an Epidemic of Cerebrospinal Fever in a Closed Community. PMID- 29012833 TI - Medical News. PMID- 29012832 TI - Clinical Observations on Cerebrospinal Meningitis in Indore. PMID- 29012834 TI - Epidemiology of Leprosy. PMID- 29012835 TI - Splenic Anaemia and Treatment by Splenectomy. PMID- 29012836 TI - Abstracts from Reports. PMID- 29012837 TI - A Plea for the Use of Concentrated Saline in Cholera. PMID- 29012838 TI - A Case of Malignant Tumour. PMID- 29012839 TI - The Transmission of Kala-Azar in India. PMID- 29012840 TI - British Spas. PMID- 29012841 TI - A Case of Guinea-Worm Infection. PMID- 29012842 TI - A Simple Technique for the Detection of Small Traces of Chloroform in Vaccine Lymph. PMID- 29012844 TI - A Case of Melanoma of Rectum. PMID- 29012843 TI - Splenectomy for Tropical Splenomegaly. PMID- 29012845 TI - Epidemic Measles in Assam. PMID- 29012846 TI - A Simple Method of Bug Destruction. PMID- 29012847 TI - Nephrosis: Its Nature and Incidence in Indians. PMID- 29012848 TI - Current Topics. PMID- 29012849 TI - A Case of Triplet Pregnancy. PMID- 29012850 TI - An Unusually Large Horny Growth. PMID- 29012851 TI - Distribution of Simple Goitre in Derbyshire. PMID- 29012852 TI - Drug Addiction in India and Its Treatment. PMID- 29012853 TI - Duration and Degree of Immunity against Smallpox Conferred by Infantile Vaccination. PMID- 29012855 TI - Conservative Surgery in Malignant Disease. PMID- 29012854 TI - A Case of Myelocytic Leukaemia with Complications. PMID- 29012856 TI - A Case of Pellagra. PMID- 29012857 TI - Abstracts from Reports. PMID- 29012858 TI - Service Notes. PMID- 29012860 TI - The Development of Ophthalmology in Bengal. PMID- 29012859 TI - Some Observations on Dysentery and Diarrhoea at Darjeeling. PMID- 29012861 TI - Drug Addiction in India. PMID- 29012863 TI - A Case of Calculus Formation in the Preputial Sac. PMID- 29012862 TI - Foetus Papyraceus. PMID- 29012864 TI - An Unusual Case of Jaundice Associated with Hodgkin's Disease. PMID- 29012866 TI - Current Topics. PMID- 29012867 TI - Medical News. PMID- 29012865 TI - A Case of Encephalitis Periaxialis: Schilder's Syndrome. PMID- 29012869 TI - Fumigation and Trapping of Mosquitoes. PMID- 29012868 TI - Some Observations on the Lactose-Fermenting Organisms Encountered in the Bacteriological Analysis of Water in the Tropics. PMID- 29012870 TI - Abstracts from Reports. PMID- 29012871 TI - A Peculiar Case of Vesico-Vaginal Fistula. PMID- 29012872 TI - The Effect of the Use of Living or Dead Suspensions of Vibrios on the Agglutination Titre. PMID- 29012874 TI - The Tuberculosis Problem in India. PMID- 29012873 TI - The New Synthetic Drugs. PMID- 29012875 TI - Current Topics. PMID- 29012876 TI - Erratum: A Fatal Case of Bronchial Asthma. AB - [This corrects the article on p. 29 in vol. 70.]. PMID- 29012877 TI - A Case of Polycystic Disease of the Kidneys. PMID- 29012878 TI - The Venereal Origin of Granuloma Inguinale. PMID- 29012880 TI - Service Notes. PMID- 29012879 TI - Acute Empyema in Childhood. PMID- 29012881 TI - A Case of a Fibromyoma of the Vaginal Wall? PMID- 29012882 TI - Observations on the Vitamin-A Value of Halibut-Liver Oil. PMID- 29012883 TI - A Strangulated Hernia. PMID- 29012884 TI - Medical News. PMID- 29012885 TI - A Large Ovarian Cyst in a Young Girl. PMID- 29012886 TI - On the Relationship between the Quinine Concentration in the Circulating Blood and Parasite Count in Monkey Malaria. PMID- 29012887 TI - A Case of Rat-Bite Fever. PMID- 29012888 TI - Granuloma Venereum. PMID- 29012889 TI - A Case of Nasal Myiasis. PMID- 29012891 TI - Values of Constants in the Analysis of GHI for Detection of Adulteration. PMID- 29012890 TI - A Simple Method of Bug Destruction. PMID- 29012892 TI - A Case of Gynaecomastia. PMID- 29012893 TI - Corneal Transplantation on Opaque Corneas. PMID- 29012894 TI - A Case of Gynaecomastia. PMID- 29012895 TI - A Case of Binocular Subluxation of the Lens in a Child. PMID- 29012896 TI - Recent Advances in Ophthalmology. PMID- 29012897 TI - Five Cases of Rhinosporidiosis, Four in Females. PMID- 29012898 TI - A Case of Retained Gangrenous Placenta. PMID- 29012899 TI - A Report on Plague in Peermade (Travancore State). PMID- 29012900 TI - Calcinosis Cutis. PMID- 29012901 TI - The Treatment of Obstruction of Lacrimal Duct and Chronic Dacryocystitis. PMID- 29012902 TI - A Small X-Ray Building for a Mofussil Hospital. PMID- 29012903 TI - Erratum: Splenectomy for Tropical Splenomegaly. AB - [This corrects the article on p. 243 in vol. 70.]. PMID- 29012904 TI - The Rate of Development of Hookworm Eggs. PMID- 29012905 TI - Current Topics. PMID- 29012906 TI - Arterial versus Venous Blood Sugar : Arterio-Venous Sugar Difference as a Criterion of the Severity of Diabetes. PMID- 29012907 TI - Ewing's Sarcoma: A Clinical and Pathological Study of a Case. PMID- 29012908 TI - The Sterility of Vaccines. PMID- 29012909 TI - Abstracts from Reports. PMID- 29012910 TI - A Note on the Vitamin B1-, B2- and C-Values of Country Liquor Prepared from the Date. PMID- 29012912 TI - Service Notes. PMID- 29012911 TI - A Case of Persistent Priapism. PMID- 29012913 TI - Evipan-Sodium: Intravenous Anaesthetic. PMID- 29012914 TI - Suspended Animation. PMID- 29012915 TI - A Case of Eclampsia: Treated with 'Chloral Hydras'. PMID- 29012916 TI - Medical News. PMID- 29012917 TI - A Note on the Relative Vitamin C-Values of Milk and Curd. PMID- 29012918 TI - Tebetren in Indian Strains of Malaria. PMID- 29012919 TI - The Essentials of Bore-Hole Latrine Construction. PMID- 29012920 TI - A Plea for the Use of Concentrated Saline in Cholera. PMID- 29012921 TI - A Case of Paroxysmal Tachycardia and Its Sequel. PMID- 29012922 TI - Service Notes. PMID- 29012923 TI - A Case of Quinine Haemoglobinuria. PMID- 29012925 TI - The Question of Marriage in Pulmonary Tuberculosis : A Critical Consideration with Special Reference to Indian Conditions. PMID- 29012924 TI - Infective Warts and Their Treatment. PMID- 29012926 TI - Abstracts from Reports. PMID- 29012927 TI - Cerebrospinal Fever in India. PMID- 29012928 TI - Investigations on Cerebro-Spinal Fever in Nasirabad (Rajputana) during the Period 1931 to 1934: Part I. PMID- 29012929 TI - Snake Venoms in Pharmacology and Therapeutics. PMID- 29012930 TI - A Record of Five Years' Ante-Natal and Infant Welfare Work on Estates in Malaya. PMID- 29012931 TI - Medical News. PMID- 29012932 TI - Drug Addiction in India and Its Treatment. PMID- 29012933 TI - Current Topics. PMID- 29012934 TI - Herpes Zoster and Sulphanilamide. PMID- 29012935 TI - An Investigation into the Toxicity of Sulphanilamide in Albino Rats and the Protective Effect of Nicotinic Acid. PMID- 29012936 TI - Observations on Inguinal Hernia, Its Treatment and Operative Technique. PMID- 29012937 TI - A Clinical Sign in Sandfly Fever. PMID- 29012938 TI - Von Ritter's Disease (Dermatitis Exfoliativa Neonatorum) Treated with Sulphapyridine. PMID- 29012939 TI - Survival of Vibrio Cholerae in Gastric Juice. PMID- 29012940 TI - Search for an Antimalarial Drug in the Indigenous Materia Medica: Part I-Alstonia Scholaris, F. Br. PMID- 29012941 TI - Notes on the Use of Cotton in Surgery, and on Plaster Technique. PMID- 29012942 TI - A Case of Multiple Fractures. PMID- 29012943 TI - A Brief Note on the Use of Congo Red in Protozoal Dysentery. PMID- 29012944 TI - Two Rare Complications of Intestinal Amoebiasis. PMID- 29012945 TI - A Case of Paroxysmal Haematuria Due to Malaria. PMID- 29012946 TI - Current Topics. PMID- 29012948 TI - Tetanic Convulsions Apparently Due to Ascariasis. PMID- 29012947 TI - Scurvy Treated with Tomato Juice. PMID- 29012949 TI - On Agricultural Malaria and Its Control with Special Reference to South India. PMID- 29012950 TI - Service Notes. PMID- 29012951 TI - Economy and Simplification in the Staining of Blood Slides. PMID- 29012952 TI - Treatment of Carbuncle with Excision. PMID- 29012953 TI - Medical News. PMID- 29012954 TI - The Treatment of Bacillary Dysentery. PMID- 29012956 TI - Abstracts from Reports. PMID- 29012955 TI - Public Health Organization: V. The Public Health Aspect of Malaria Control. PMID- 29012957 TI - Vitex Peduncularis-An Antihaemolytic Agent. PMID- 29012958 TI - An Unusual Injury. PMID- 29012959 TI - A Case of Diphtheria of the Glans Penis. PMID- 29012961 TI - Service Notes. PMID- 29012960 TI - A Foreign Body in the Rectum for Fifteen Years? PMID- 29012962 TI - Abstracts from Reports. PMID- 29012963 TI - A Case of Iron Encephalopathy. PMID- 29012964 TI - Injuries of the Skull. PMID- 29012965 TI - The AEtiology of Blackwater Fever. PMID- 29012966 TI - Mass Treatment with Injectable Atebrin. PMID- 29012967 TI - The Prognostic Value of the Variation in the Arneth Count in Cases of Asthma Treated with Auto-Vaccine. PMID- 29012968 TI - The Middle-Aged Patient, and Later: A Lecture to Post-Graduates. PMID- 29012969 TI - The Radio-Activity of the Thermal Springs of Rajgir. PMID- 29012970 TI - Rheumatic Heart Disease in the Bombay Deccan. PMID- 29012971 TI - Atebrin-Plasmochin in the Treatment of Malaria. PMID- 29012972 TI - Current Topics. PMID- 29012973 TI - Multiple Paralysis Following Measles. PMID- 29012975 TI - Nutrition Requirements. PMID- 29012974 TI - Medical News. PMID- 29012976 TI - The Treatment of Lobar Pneumonia with Intravenous Injections of Alcohol. PMID- 29012977 TI - Notes on a Case of Acute Lead Encephalopathy. PMID- 29012978 TI - A Case of Pyo-Peritoneum. PMID- 29012979 TI - Ephedrine, and the Reduction of a Strangulated Hernia. PMID- 29012981 TI - Current Topics. PMID- 29012980 TI - A Case of Malignant Tumour of the Stomach in a Male with Transposition of the Viscera. PMID- 29012982 TI - The Trend of Immunity Studies in Malaria. PMID- 29012983 TI - An Investigation on the Effects of Evipan Sodium on the Blood Sugar of the Rabbit. PMID- 29012984 TI - Fluorescein in Lepra Reaction. PMID- 29012985 TI - Heterotopic Bone in Elephantoid Tissues. PMID- 29012986 TI - Service Notes. PMID- 29012987 TI - Composting of Town Refuse by the 'Edelmist' Process. PMID- 29012988 TI - The Control of the Drug Trade. PMID- 29012990 TI - Medical News. PMID- 29012989 TI - Some Observations on the Haemolysis Caused by Snake Venoms: A Preliminary Note. PMID- 29012991 TI - Abstracts from Reports. PMID- 29012992 TI - The Feeding of Infants in India. PMID- 29012993 TI - Medical Research in India. PMID- 29012995 TI - Medical News. PMID- 29012994 TI - The Distribution of Indian Tick Typhus with Notes on Laboratory Findings. PMID- 29012996 TI - A Note on an Unusual Source of Contamination of Well Water. PMID- 29012997 TI - A Practical Way of Dealing with AEdes AEgypti (Stegomyia Fasciata) Mosquito Breeding in Country Craft. PMID- 29012999 TI - Corrigendum. AB - [This corrects the article on p. 683 in vol. 70.]. PMID- 29012998 TI - Bacteriophage in the Treatment of Cholera. PMID- 29013000 TI - Jhin-Jhinia and Its Cure. PMID- 29013001 TI - Service Notes. PMID- 29013002 TI - Unusual Identification of Explosive. PMID- 29013003 TI - Epithelioma Adenoides Cysticum: Reports of Three Cases. PMID- 29013004 TI - A Case of Thrombo-Angiitis Obliterans Treated by Femoral Peri-Arterial Sympathectomy. PMID- 29013005 TI - Training in Pharmacy in India. PMID- 29013006 TI - Petit Mal or Pyknolepsy. PMID- 29013007 TI - Jhin-Jhinia, or Neuromimesis? PMID- 29013008 TI - Infection with Bertiella Studeri. PMID- 29013009 TI - Against Orthodoxies in Rabies. PMID- 29013010 TI - Non-Plague Rat Mortality. PMID- 29013011 TI - The Treatment of Lobar Pneumonia with Intravenous Injections of Alcohol. PMID- 29013012 TI - Intestinal Tuberculosis. PMID- 29013013 TI - Pregnancy, with Partially Occluded Vagina. PMID- 29013014 TI - Current Topics. PMID- 29013015 TI - Abstracts from Reports. PMID- 29013017 TI - Tropical Typhus. PMID- 29013016 TI - Bacteriological Studies in Epidemic Dropsy. PMID- 29013018 TI - A Peculiar Complication of Labour. PMID- 29013019 TI - Treatment of Chronic Diarrhoea. PMID- 29013020 TI - Medical News. PMID- 29013021 TI - Pitfalls in Ophthalmic Practice. PMID- 29013022 TI - A-O Tuberculin in Ophthalmology. PMID- 29013023 TI - A New Type of Choleraphage-Type M. PMID- 29013024 TI - Intestinal Tuberculosis. PMID- 29013026 TI - Abstracts from Reports. PMID- 29013025 TI - Natural Spirillum Minus Infection in White Mice. PMID- 29013027 TI - A Preliminary Note on the Treatment of Neuro-Syphilis with Monkey Malaria. PMID- 29013028 TI - Short-Wave Therapy. PMID- 29013030 TI - Current Topics. PMID- 29013029 TI - 'Man-Made' Malaria in India. PMID- 29013031 TI - Response to Pilocarpine in Cases of Asthma. PMID- 29013032 TI - Late Reactions after Anti-Cholera Inoculation. PMID- 29013033 TI - Service Notes. PMID- 29013035 TI - Technique for Putting up Fracture of the Clavicle. PMID- 29013034 TI - The So-Called Mystery Disease of Calcutta (Jhin-Jhinia or Thartharia). PMID- 29013036 TI - The Feeding of Infants in India. PMID- 29013037 TI - Description of Bacterium Pseudo-Carolinus. PMID- 29013038 TI - An Unusual Case of Suicidal Stabbing. PMID- 29013039 TI - Service Notes. PMID- 29013040 TI - Abstracts from Reports. PMID- 29013041 TI - A Depressed Compound Fracture of the Skull with Infection. PMID- 29013042 TI - A Few Points on the Technique of Gastro-Jejunostomy. PMID- 29013043 TI - A Foetus with Its Placenta Adherent to the Brain. PMID- 29013044 TI - A Note on the Experimental Infection of Dogs with Dracontiasis. PMID- 29013045 TI - Current Topics. PMID- 29013046 TI - A Study of One Hundred Cases of Dermatitis. PMID- 29013047 TI - The Description of an Old Type of Privy. PMID- 29013048 TI - Studies on the Action of Antimalarial Remedies on Monkey Malaria: The Relationship between the Concentration of Atebrin in the Circulating Blood and Parasite Count. PMID- 29013050 TI - An Arrow Head in the Mouth for Three Years. PMID- 29013049 TI - Intra-Uterine Vaccinia in Pregnant Animals. PMID- 29013051 TI - A Simple Method of Broncho-Radiography. PMID- 29013053 TI - Dracunculus Medinensis. PMID- 29013052 TI - Hyperpyrexia in Datura Poisoning. PMID- 29013054 TI - A Case of Persistent Hiccup. PMID- 29013056 TI - Cholera and Intestinal Helminths. PMID- 29013057 TI - Two Cases of Pancreatic Deficiency. PMID- 29013055 TI - A Village Mosquito-Trap. PMID- 29013058 TI - Medical News. PMID- 29013059 TI - Spirillum Fever Caused by a Monkey Bite. PMID- 29013060 TI - Three Cases of Adherent Retrocaecal Appendix. PMID- 29013061 TI - Treatment of 'Sutika' (Puerperal Diarrhoea) by Injection of Grape Sugar Solution. PMID- 29013062 TI - Injuries of the Skull. PMID- 29013063 TI - Traumatic Rupture of Pancreas with Formation of a Cyst. PMID- 29013065 TI - Asthma. PMID- 29013064 TI - An Extensive Empyema. PMID- 29013067 TI - Service Notes. PMID- 29013066 TI - Notes on Pneumonia in a Tea Garden in Assam. PMID- 29013068 TI - Infection with Bertiella Studeri. PMID- 29013069 TI - A Practical Way of Dealing with AEdes AEgypti (Stegomyia Fasciata) Mosquito Breeding in Country Craft. PMID- 29013070 TI - A Case of Rhino-Meningorrhea. PMID- 29013071 TI - Immunological Methods in the Determination of Infection in a Random Sample of Hospital Admissions: Part I (The Frequency and Concentration of 'H' and 'O' Agglutinins for the Bacilli of the Typhoid-Paratyphoid Group in 280 Individuals Admitted into the Carmichael Hospital for Tropical Diseases, Calcutta). PMID- 29013072 TI - Heat Stroke and Carbon Dioxide. PMID- 29013073 TI - Medical News. PMID- 29013074 TI - More on Hill Malaria. PMID- 29013076 TI - Abstracts from Reports. PMID- 29013075 TI - Velocity, Silt and Larval Drift. PMID- 29013077 TI - Intravenous Alcohol in Pneumonia. PMID- 29013078 TI - Current Topics. PMID- 29013079 TI - The Population Problem in India. PMID- 29013080 TI - A Case of Gas Gangrene. PMID- 29013082 TI - Arsenical Intolerance Overcome by Desensitization. PMID- 29013081 TI - Tuberculosis in Some Rare Situations, Namely Tonsils and Uterus. PMID- 29013083 TI - Two Cases of Accidental Datura Poisoning. PMID- 29013084 TI - Examination of Seminal Stains in Medico-Legal Cases. PMID- 29013085 TI - Observations on the Relative Value of Atebrin and Quinine as Therapeutic Agents in Malaria. PMID- 29013086 TI - Epidemiology of Malaria. PMID- 29013087 TI - A Case of Scorpion Bite. PMID- 29013089 TI - The Treatment of Rhinosporidiosis in Man Based on the Study of Sixty Cases. PMID- 29013088 TI - Atebrin by Injection vs. Quinine in a Tea-Garden Practice. PMID- 29013090 TI - Service Notes. PMID- 29013092 TI - Dietary and Nutritional Standards in India. PMID- 29013091 TI - Intestinal Tuberculosis. PMID- 29013093 TI - Current Topics. PMID- 29013094 TI - A Case of Fibro-Sarcoma of the Orbit. PMID- 29013096 TI - Abstracts from Reports. PMID- 29013095 TI - Drug Addiction in India and Its Treatment. PMID- 29013097 TI - Immunological Methods in the Determination of Infection in a Random Sample of Hospital Admissions: Part III (The Frequency and Concentration of Agglutinins for Bact. pseudo-carolinus in a Series of 218 Hospital Patients). PMID- 29013098 TI - A Case of Cerebral Malaria Causing Persistent Loss of Eyesight. PMID- 29013099 TI - Medical News. PMID- 29013100 TI - Paralysis after Measles. PMID- 29013101 TI - Gold Therapy in Pulmonary Tuberculosis. PMID- 29013102 TI - A Note on Cases of Typhus Fever in Burma and Their Distribution. PMID- 29013103 TI - A Note on Two Leopard Bites. PMID- 29013104 TI - Pellagra in Vizagapatam. PMID- 29013105 TI - Changes in Certain Chemical Constituents of the Blood in Kala-Azar. PMID- 29013106 TI - AEtiology of Primary Glaucoma. PMID- 29013108 TI - Service Notes. PMID- 29013107 TI - Report on a Fatal Case of Agranulocytosis. PMID- 29013110 TI - Clavicle in Two Parts. PMID- 29013109 TI - Strangulated Hernia. PMID- 29013111 TI - Intestinal Tuberculosis and Auro-Therapy. PMID- 29013112 TI - An Untoward Symptom in a Case of Sodium-Evipan Anaesthesia. PMID- 29013113 TI - An Abdominal Pregnancy Developing to Full Term. PMID- 29013114 TI - A Comparative Study of the Modified Kline Test with the Wassermann and Kahn Tests on 946 Blood Samples. PMID- 29013115 TI - Observations on the Intra-Ocular Pressure in Cats. PMID- 29013116 TI - A Remarkable Monster. PMID- 29013117 TI - Guinea-Worm Infection of Cyclops in Nature. PMID- 29013119 TI - Abstracts from Reports. PMID- 29013118 TI - The Treatment of Peptic Ulcer. PMID- 29013120 TI - A Biological Method for the Control of Dracontiasis. PMID- 29013121 TI - An Unusual Foreign Body in the Rectum. PMID- 29013122 TI - Bilateral Raynaud's Disease Treated by Double Peri-Arterial Sympathectomy. PMID- 29013123 TI - A Case of Hysterical Monoplegia. PMID- 29013124 TI - An Unusual Sebaceous Cyst. PMID- 29013125 TI - Serum Treatment in a Case of Acute Staphylococcal Septicaemia. PMID- 29013127 TI - Heredity in Ichthyosis. PMID- 29013126 TI - Current Topics. PMID- 29013128 TI - A Huge Goitre. PMID- 29013129 TI - Proximate Analysis of a Native Beer Pachwai of the Aboriginal Tribes in Bengal. PMID- 29013130 TI - Antiseptic Properties of Raw Cod-Liver Oil. PMID- 29013131 TI - A Drop Pipette for Use in the Kahn Test. PMID- 29013132 TI - Medical News. PMID- 29013133 TI - Sedimentation of Red Blood Cells in Glaucoma and Other Ocular Diseases. PMID- 29013134 TI - Treatment of an Inoperable Pancreatic Cyst. PMID- 29013135 TI - Sodium Mandelate in the Treatment of Bacillus Coli Infection. PMID- 29013136 TI - Reaction after Anti-Cholera Inoculations. PMID- 29013137 TI - A Giant Dermoid Cyst. PMID- 29013138 TI - Cystic Degeneration of Glans Penis. PMID- 29013139 TI - Experience with Cancer of the Larynx, Pharynx and the Adjoining Regions. PMID- 29013140 TI - Abstracts from Reports. PMID- 29013141 TI - Nitrous Oxide and Oxygen Anaesthesia for Major Surgery. PMID- 29013142 TI - Infantile Eczema. PMID- 29013143 TI - Erratum: Against Orthodoxies in Rabies. AB - [This corrects the article on p. 69 in vol. 71.]. PMID- 29013144 TI - X-Ray Appearances Seen 24 Years after Healing in a Case of Extensive Tuberculosis of Lung. PMID- 29013145 TI - Conjugal Venereal Granuloma. PMID- 29013146 TI - A Case of Elephantoid Tumour of the Labium Majus. PMID- 29013147 TI - Experimental Studies on Atebrin. PMID- 29013148 TI - Treatment of Scorpion Stings. PMID- 29013150 TI - Conservative Management of Bowels in Pneumonia. PMID- 29013149 TI - A Case of Prolonged Hunger-Strike. PMID- 29013151 TI - Enteric Fever in Vizagapatam. PMID- 29013152 TI - Dermal Leishmaniasis in China. PMID- 29013154 TI - Medical News. PMID- 29013153 TI - Vaccine Treatment of Typhoid. PMID- 29013155 TI - Service Notes. PMID- 29013156 TI - A Case of Human Infection with Dientamoeba Fragilis Jepps and Dobell, 1918, in Calcutta. PMID- 29013158 TI - Current Topics. PMID- 29013157 TI - A Case of Malaria Complicated with Erythematous Rash. PMID- 29013159 TI - Primary Pyocyanea Infection of the Skin. PMID- 29013160 TI - The Treatment of Urinary Infections. PMID- 29013161 TI - A Leech in the Nose. PMID- 29013162 TI - Thrombophlebitis Migrans. PMID- 29013163 TI - The Classification of the Anaemias: A Resume of a Clinical Lecture. PMID- 29013164 TI - Treatment of Syphilis by Modenol. PMID- 29013165 TI - Abstracts from Reports. PMID- 29013166 TI - Heliotherapy or Sun Cure. PMID- 29013167 TI - A Comparative Study of the Action of Atebrin and Atebrin-Plasmochin Combination on Indian Strains of Malaria. PMID- 29013168 TI - Service Notes. PMID- 29013169 TI - Gastric Analysis in Asthma. PMID- 29013170 TI - Hydrophobia Simulating Acute Transverse Myelitis at the Onset. PMID- 29013172 TI - Medical News. PMID- 29013171 TI - Role of Infection in the AEtiology of Infantile Cirrhosis of the Liver. PMID- 29013173 TI - Antiseptic Properties of Raw Cod-Liver Oil. PMID- 29013174 TI - Current Topics. PMID- 29013175 TI - The Effect of the Ingestion of Vitamin C on the Vitamin-C Concentration of the Milk of Lactating Women. PMID- 29013176 TI - Immunological Methods in the Determination of Infection in a Random Sample of Hospital Admissions: Part II (The Frequency and Concentration of Agglutinins for Proteus X Strains in a Series of Hospital Patients). PMID- 29013177 TI - Erratum: Intravenous Alcohol in Pneumonia. AB - [This corrects the article on p. 276b in vol. 71.]. PMID- 29013179 TI - Cysticercosis in Man. PMID- 29013178 TI - A Note on Museum Making III: A Method for Preserving and Mounting Pathological Fluids. PMID- 29013180 TI - A Case of Uterus Bicornis with Advanced Pregnancy Complicated by a Large Pelvic Cyst. PMID- 29013181 TI - Investigation of Yaws (Koya Disease) in Warangal. PMID- 29013182 TI - Two Cases of Pyrexia from B. Columbensis. PMID- 29013183 TI - A Note on the Use of Cyanogas 'A' Dust as a Raticide and Pulicide. PMID- 29013184 TI - An Apparatus for the Distribution of Antigen Emulsion in the Kahn Test. PMID- 29013185 TI - Multiple Stones in the Bladder. PMID- 29013186 TI - Osteomalacia; Torsion of the Pregnant Uterus. PMID- 29013187 TI - Electrocardiographic Changes in Epidemic Dropsy. PMID- 29013188 TI - A Melanotic Sarcoma of the Anal Region. PMID- 29013189 TI - Medical Interference. PMID- 29013190 TI - The Treatment of Piles. PMID- 29013192 TI - Milk. PMID- 29013193 TI - The Clinical Aspect of Placenta Praevia and Its Management in Indian Conditions. PMID- 29013191 TI - The Protein and Mineral Values of Some Cooked Bengali Diets. PMID- 29013194 TI - A Case of Acute Infective Myelitis (Influenzal) Treated with Milk Injections. PMID- 29013195 TI - The Rarity of the Male Enterobius Vermicularis. PMID- 29013196 TI - Carbuncle Complicated with Erysipelas. PMID- 29013197 TI - A Stone in the Prepuce. PMID- 29013199 TI - Service Notes. PMID- 29013198 TI - Serum Complement in Relation to Vitamin-C Deficiency in Guinea-Pigs. PMID- 29013201 TI - Current Topics. PMID- 29013200 TI - Puerperal Sepsis: A Review. PMID- 29013202 TI - Combined Myopathy and Neuropathy. PMID- 29013204 TI - Medical News. PMID- 29013203 TI - Clinical Study of Sixty-Three Cases of Oriental Sore. PMID- 29013206 TI - Medical News. PMID- 29013205 TI - Abstracts from Reports. PMID- 29013207 TI - Service Notes. PMID- 29013208 TI - Four Maggot-Like Worms Removed from the Left Conjunctival Sac of a Patient. PMID- 29013209 TI - Radiology of the Heart and Great Vessels. PMID- 29013211 TI - Current Topics. PMID- 29013210 TI - A Case of Paraplegia and Hydrophobia Following a Full Course of Anti-Rabic Treatment. PMID- 29013213 TI - Stone in the Urethra of a Baby. PMID- 29013212 TI - Significance of Florence Test for Seminal Stains. PMID- 29013214 TI - Correspondence. PMID- 29013215 TI - Deeds of Violence in India in 1935-36 and Other Crimes in Which Serology Plays a Part. PMID- 29013216 TI - The Denuded Penis after Operation for Elephantoid Scrotum. PMID- 29013217 TI - Haematokolpos and Haematometra. PMID- 29013218 TI - The Mortality of Operations for Vesical Calculus in India. PMID- 29013219 TI - Rheumatic Fever in the Punjab. PMID- 29013220 TI - Calcium Oxalate Calculus in the Urethra. PMID- 29013221 TI - Experience with Russell's Viper Venom. PMID- 29013223 TI - Cod-Liver Oil in Surgery. PMID- 29013224 TI - Abstracts from Reports. PMID- 29013222 TI - Carcinoid Tumour of the Appendix. PMID- 29013226 TI - Fairs and Festivals in India. PMID- 29013225 TI - A Case of Haemoglobinuria Caused by Plasmochin Taken as a Prophylactic against Malaria. PMID- 29013227 TI - The Eggs of Taenia Solium and Taenia Saginata. PMID- 29013228 TI - The Epidemiology of Leprosy. PMID- 29013230 TI - Current Topics. PMID- 29013229 TI - Abstracts from Reports. PMID- 29013231 TI - Diet and Adaptation to the Tropics. PMID- 29013233 TI - Infantile Biliary Cirrhosis. PMID- 29013232 TI - Individual Variations in the Effectiveness of Synthetic Antimalarial Drugs (A Preliminary Note). PMID- 29013234 TI - The Giant-Cell Tumour of Bone: With a Report of Six Cases. PMID- 29013235 TI - The Treatment of Pityriasis Rosea. PMID- 29013236 TI - Allergy. PMID- 29013237 TI - A Record of Rhinosporidial Polypi with Some Observations on the Mode of Infection. PMID- 29013239 TI - Service Notes. PMID- 29013238 TI - Malignant Disease of the Prostate in a Small Child. PMID- 29013240 TI - Fatal Case of Acute Gonorrhoea (Septicaemia with Ulcerative Endocarditis). PMID- 29013241 TI - Prophylaxis of Chicken-Pox by Inoculation with Vesicular Fluid. PMID- 29013242 TI - Hodgkin's Disease of the Pelebstein Type: Some Unusual Findings. PMID- 29013243 TI - The Bisulphite-Binding Power of the Blood in Cases of Epidemic Dropsy, Anaemia and Malaria and Its Possible Bearing on a Vitamin-B Deficiency. PMID- 29013245 TI - Medical News. PMID- 29013244 TI - Radiological and Laboratory Investigations of Chronic Gastro-Intestinal Disturbances in the Tropics. PMID- 29013246 TI - Abstracts from Reports. PMID- 29013247 TI - Use of Prontosil Album in Cellulitis of the Hand. PMID- 29013248 TI - Study of Commercial Bacteriophages: I. Bacteriophages Active against the Dysentery Group of Organisms. PMID- 29013249 TI - Races of A. Stephensi Liston, 1901. PMID- 29013250 TI - Epidemic Dropsy in Cawnpore (U. P.). PMID- 29013251 TI - Current Topics. PMID- 29013252 TI - The Incidence of Clostridium Tetani in the Soil of Calcutta. PMID- 29013253 TI - Further Experience with Tetrachlorethylene. PMID- 29013254 TI - Non-Tuberculous Affections of the Lungs Confused with Pulmonary Tuberculosis. PMID- 29013255 TI - A Case of Syndactylism. PMID- 29013256 TI - A Case of Indian Typhus. PMID- 29013258 TI - Some Common Conditions Treated by Ultra-Violet Radiations. PMID- 29013257 TI - Snake Venom in Therapeutics. PMID- 29013259 TI - A Note on a Case of Brucella Abortus Infection in Aden. PMID- 29013260 TI - Medical News. PMID- 29013261 TI - Service Notes. PMID- 29013262 TI - The Problem of Cancer. PMID- 29013263 TI - Types of Typhoidphage and a Note on the Protective Value of Typhoidphage in Animal Experiments. PMID- 29013264 TI - A Modified Village Mosquito Trap. PMID- 29013265 TI - A Case of Lead Encephalopathy. PMID- 29013266 TI - A Case of Cancrum Oris as a Complication of Bacillary Dysentery. PMID- 29013267 TI - A Plea for a Forward Public-Health Policy in India. PMID- 29013268 TI - Protamine Zinc Insulin. PMID- 29013269 TI - Service Notes. PMID- 29013271 TI - A Case of Pulmonary Tuberculosis, Complicated with Syphilis. PMID- 29013270 TI - Strangulated Hernia: Treated by Resection and Enterorrhaphy. PMID- 29013272 TI - Prontosil in Acute Rheumatic Polyarthritis. PMID- 29013273 TI - Results of Splenectomy for Tropical Splenomegaly: An Analysis of Thirty-Three Cases. PMID- 29013274 TI - A Short Note on the Diagnosis of Pulmonary Tuberculosis. PMID- 29013275 TI - Current Topics. PMID- 29013277 TI - Hydatid Disease: A Case Report. PMID- 29013276 TI - Acute Inflammation of the Attic-Its Diagnosis and Treatment. PMID- 29013279 TI - Medical News. PMID- 29013278 TI - A Case of Rupture of the Vagina. PMID- 29013280 TI - A Severe Case of Scrub Typhus. PMID- 29013281 TI - Sodium Evipan Anaesthesia. PMID- 29013282 TI - Diet and Public Health in India. PMID- 29013283 TI - Telerontgenography of the Heart in Epidemic Dropsy. PMID- 29013284 TI - Endemic Fluorosis in the Nellore District of South India. PMID- 29013285 TI - The Effects of the Injections of Milk Preparations in Leprosy. PMID- 29013286 TI - Abstract from Report. PMID- 29013287 TI - A Case of Full-Term Pregnancy with Unruptured Hymen. PMID- 29013288 TI - Oriental Sore Simulating Leprosy. PMID- 29013289 TI - Dermatitis Artefacta. PMID- 29013290 TI - A Fatal Case of Cerebral Malaria Caused by Plasmodium Malariae. PMID- 29013291 TI - Cholera in Kashmir in 1935 with Special Reference to Certain Aspects of the Value of Protective Inoculation. PMID- 29013292 TI - Congenital Obstruction of the Anus. PMID- 29013293 TI - Haematemesis in a Case of Malaria. PMID- 29013294 TI - An Apparently Successful Case of Cardiac Massage. PMID- 29013295 TI - Service Notes. PMID- 29013296 TI - Chemotherapy in Bacterial Infections. PMID- 29013297 TI - Clinical Study of Sixty-Three Cases of Oriental Sore. PMID- 29013298 TI - Some Uncommon Affections Seen at an Eye Clinic. PMID- 29013299 TI - Correspondence. PMID- 29013301 TI - Letzko's Operation as a Treatment for the 'Failed Forceps' Case. PMID- 29013300 TI - Treatment of Plague Cases with Convalescent Human Serum. PMID- 29013302 TI - A Comparative Study of the Action of Atebrin and Atebrin-Plasmochin Combination on Indian Strains of Malaria: Part II. PMID- 29013303 TI - Acute Volvulus: A Case Report. PMID- 29013304 TI - Dissecting Aneurysm-Report of a Case. PMID- 29013305 TI - Surgical Treatment of Non-Paralytic Squint. PMID- 29013306 TI - Medical Practice in India: The Economic Outlook. PMID- 29013307 TI - Current Topics. PMID- 29013308 TI - Abstracts from Reports. PMID- 29013310 TI - A Study of Thirty-Nine Cases of Auricular Fibrillation. PMID- 29013309 TI - Insulin Anaphylaxis. PMID- 29013311 TI - A Case of Complete Encephalocele and Series of Developmental Defects in the Same Family. PMID- 29013312 TI - A Stable Solution of Antimony for the Treatment of Kala-Azar. PMID- 29013313 TI - Medical News. PMID- 29013314 TI - The Calcutta Filtered Water Supply. PMID- 29013315 TI - Arsenic in Human Tissues and Excreta. PMID- 29013317 TI - Service Notes. PMID- 29013316 TI - Treatment of Malaria in Children with Atebrin-Musonate. PMID- 29013318 TI - A Case of Tick Typhus at Allahabad. PMID- 29013319 TI - Anaemia in Tea-Garden Labour Forces. PMID- 29013320 TI - Medical News. PMID- 29013321 TI - Fatal Anaphylactic Shock. PMID- 29013322 TI - Abstracts from Reports. PMID- 29013324 TI - The Nutritive Value of Indian Foods and the Planning of Diets. PMID- 29013323 TI - Current Topics. PMID- 29013325 TI - The Operative Treatment of Vesico- and Vesico-Urethro Vaginal Fistulae by the Vaginal Route with Case Notes on ThirtyThree Cases. PMID- 29013326 TI - An Unusual Result of an Accident. PMID- 29013327 TI - The Anopheles Sundaicus Invasion of Lower Bengal. PMID- 29013328 TI - Public Health Aspects of Filariasis in India. PMID- 29013329 TI - A Syncopal Form of Angina Pectoris: An Electrocardiographical Study. PMID- 29013330 TI - Vitamin A, as Determined by the Blue Units of the Antimony Trichloride Test, in the Livers of Malnourished Children. PMID- 29013331 TI - The Treatment of Opium Habit with Lecithin and Glucose. PMID- 29013332 TI - A Short Note on the Use of Pneumonia Stock Vaccine in the Treatment of the Pneumonias. PMID- 29013333 TI - Fireside Fantasies. PMID- 29013334 TI - Current Topics. PMID- 29013335 TI - Electrodialysis in the Purification of Concentrated Serum Antitoxin. PMID- 29013336 TI - Study of 110 Cases of Dengue Fever in the Madras Penitentiary. PMID- 29013337 TI - Medical News. PMID- 29013338 TI - Bacterium Pseudo-Carolinus Infection of the Bladder. PMID- 29013339 TI - A Note on Health Unit Work. PMID- 29013341 TI - Public Health Propaganda and Education. PMID- 29013340 TI - A Case of Ectopic Gestation Complicated by a Coexistent Unrelated Pelvic Abscess. PMID- 29013342 TI - Service Notes. PMID- 29013343 TI - Observations on Prolapse of the Uterus and Its Management in India. PMID- 29013344 TI - Prognostic Significance of Icterus Index in Lobar Pneumonia. PMID- 29013346 TI - Abstracts from Reports. PMID- 29013345 TI - A Note on a Cheap Substitute for a Shadowless Lamp for Operation Theatres. PMID- 29013347 TI - Malaria and Its Treatment by the Synthetic Remedies: Atebrin and Plasmochin. PMID- 29013348 TI - Recurrent Swelling of the Parotid Glands with the Report of a Case. PMID- 29013349 TI - Head Injuries: A Clinical Lecture. PMID- 29013350 TI - Apparatus for Leprosy Clinic. PMID- 29013352 TI - School Children and Dental Disease. PMID- 29013351 TI - A Malignant Cystic Haemangio-Blastoma of the Cerebellum. PMID- 29013353 TI - Medical News. PMID- 29013354 TI - Myeloid Leukaemia: The Treatment by Deep X-Rays. PMID- 29013355 TI - Affections of the Eye in the Malarial Fevers and Kala-Azar. PMID- 29013357 TI - The Use of Gold in Pulmonary Tuberculosis. PMID- 29013356 TI - Gangrene of the Cervix Uteri. PMID- 29013358 TI - Clinical Study of Sixty-Three Cases of Oriental Sore. PMID- 29013359 TI - Treatment of Anaemia. PMID- 29013360 TI - Service Notes. PMID- 29013361 TI - The Presence of Anopheles Sundaicus ('Ludlowi') on the Chilka Lake. PMID- 29013362 TI - Current Topics. PMID- 29013363 TI - Cyanide Poisoning and Its Treatment with Antidotes. PMID- 29013364 TI - Cobra Venom in Therapeutics. PMID- 29013365 TI - Pyrexia Simulating That of Enteric Fever Caused by Ps. Pyocyaneus in Children. PMID- 29013366 TI - Abstracts from Reports. PMID- 29013367 TI - Menstruation at the Age of 31/2 Years. PMID- 29013368 TI - Yatren in Infection with Indian Strains of E. Histolytica (Chronic Intestinal Amoebiasis). PMID- 29013369 TI - The Relation of Systemic Blood Pressure to Intra-Ocular Pressure. PMID- 29013370 TI - A Malignant Tumour Affecting the Knee Joint. PMID- 29013371 TI - Current Topics. PMID- 29013372 TI - Guinea-Worm. PMID- 29013373 TI - Development of Health Education Work in United Provinces. PMID- 29013374 TI - A Case of Cataplexy. PMID- 29013375 TI - The Occurrence of Weil's Disease in India. PMID- 29013376 TI - Abstracts from Reports. PMID- 29013377 TI - A Case of Datura Poisoning with Hyperpyrexia. PMID- 29013378 TI - Lead Poisoning from the Lining of Copper or Brass Cooking Utensils, with the Report of a Case. PMID- 29013379 TI - Carcinoma of the Penis in a Young Man. PMID- 29013380 TI - A Case of Vesicular Mole. PMID- 29013381 TI - Transplantation of Ureters into the Pelvic Colon. PMID- 29013382 TI - A Case of Ectopic Left Kidney. PMID- 29013383 TI - A Case of Spontaneous Haemorrhage from the Skin. PMID- 29013384 TI - Medical News. PMID- 29013385 TI - A Case of Convulsions. PMID- 29013386 TI - Spinal Anaesthesia. PMID- 29013387 TI - Structural Changes in the Parathyroids in Vitamin Deficiency. PMID- 29013388 TI - A Note on a Circumscribed Outbreak of a Typhus-Like Fever in Muzaffargarh District, South-Western Punjab. PMID- 29013389 TI - The Chemistry of Calcium in Tuberculosis. PMID- 29013391 TI - Further Research on Epidemic Dropsy. PMID- 29013390 TI - Service Notes. PMID- 29013393 TI - Sanitary Improvements through Village Health Leagues. PMID- 29013392 TI - Anaemia of Pregnancy. PMID- 29013394 TI - Further Research on Epidemic Dropsy. PMID- 29013395 TI - Study of 110 Cases of Dengue Fever in the Madras Penitentiary. PMID- 29013396 TI - The Effect of Reduced Pressure Combined with Increased Temperature on the Viability of Bed Bugs and of Their Eggs. PMID- 29013397 TI - A Colour Chart for the Determination of Hydrogen-Ion Concentration. PMID- 29013398 TI - Clearance of Pistia Stratiotes as a Control Measure for F. Malayi Infection. PMID- 29013399 TI - Sulphanilamide: The Second Phase. PMID- 29013400 TI - Service Notes. PMID- 29013401 TI - Experimental Investigation into the Duration of Tolerance to Re-Infection in Monkey Malaria. PMID- 29013402 TI - Gnathostomiasis in Human Beings. PMID- 29013403 TI - Intestinal Disorders in Children Caused by Suckling in Pregnant Mother. PMID- 29013404 TI - Medical News. PMID- 29013405 TI - Abstracts from Reports. PMID- 29013406 TI - The Use of Tea in the Treatment of Burns. PMID- 29013408 TI - Renal Efficiency in Glaucomatous Patients. PMID- 29013407 TI - A Case of Erythroderma Desquamativa (Leiner-Moussous) in an Indian Child. PMID- 29013409 TI - Electrocardiographic Changes in Beri-Beri. PMID- 29013410 TI - Quinine Tolerance in Pregnancy. PMID- 29013411 TI - Interatrial Septal Defect with Mitral Insufficiency of Congenital Origin. PMID- 29013412 TI - Organization of a Blood Transfusion Service in a District Hospital. PMID- 29013413 TI - The Use of Cod-Liver Oil in Infected Wounds. PMID- 29013414 TI - Litholapaxy in a Case of Cystocele. PMID- 29013416 TI - Current Topics. PMID- 29013417 TI - The Increasing Value of Modern Sanatorium Treatment as Judged by the After Histories of the Patients. PMID- 29013415 TI - Sex Education. PMID- 29013418 TI - Medical News. PMID- 29013419 TI - Tuberculosis in Infants and Children. PMID- 29013420 TI - Current Topics. PMID- 29013422 TI - Service Notes. PMID- 29013423 TI - Pulmonary Tuberculosis and Kala-Azar: A Fatal Combination. PMID- 29013421 TI - The Applicability of Phrenic Evulsion in Pulmonary Tuberculosis at the Out Patients' Department of a City Hospital. PMID- 29013424 TI - Thoracoscopic Examination and Cauterization of Adhesions: Intrapleural Pneumolysis. PMID- 29013425 TI - The Treatment of Cervical Glandular Tuberculosis. PMID- 29013426 TI - A Case of Hydatid Cyst of the Lung, with Post-Operative Tuberculous Involvement. PMID- 29013427 TI - Oleothorax in the Treatment of Pleuro-Pulmonary Tuberculosis. PMID- 29013428 TI - The Significance of a High Incidence of Xenopsylla Braziliensis Baker. PMID- 29013429 TI - Some Observations on Chrysotherapy in Pulmonary Tuberculosis. PMID- 29013430 TI - Oxygenation of the Peritoneal Cavity in the Treatment of Tuberculosis of the Abdomen. PMID- 29013431 TI - Intra-Pleural Pressure: Interpretation of Manometric Readings in Therapeutic Artificial Pneumothorax. PMID- 29013432 TI - The Special Tuberculosis Number. PMID- 29013433 TI - Adrenal Cortical Extract in Cholera. PMID- 29013434 TI - King George Thanksgiving (Anti-Tuberculosis) Fund. PMID- 29013435 TI - An Analysis of Artificial Pneumothorax Treatment in 1,039 Patients. PMID- 29013436 TI - Thoracoplasty in Pulmonary and Pleural Tuberculosis. PMID- 29013437 TI - The Tuberculosis Problem in India. PMID- 29013438 TI - Abstracts from Reports. PMID- 29013439 TI - Treatment of Tuberculous Haemoptysis by Subcutaneous Emphysema. PMID- 29013440 TI - Rheumatic Heart Disease. PMID- 29013441 TI - Role of Calcium Gluconate and Iodine in Whooping Cough. PMID- 29013442 TI - The Future of Medical Organization in India. PMID- 29013443 TI - An Unusual Complication after Operation for Removal of Tonsils and Adenoids. PMID- 29013444 TI - A Note on Dried Blood Plasma and Its Preparation in India. PMID- 29013446 TI - Medical News. PMID- 29013445 TI - A Review of 274 Cases of Lobar Pneumonia Treated with M. & B. 693. With an Analysis of the Less Successful Responses. PMID- 29013447 TI - Abstracts from Reports. PMID- 29013448 TI - Service Notes. PMID- 29013449 TI - Organization of Public Health and Medical Services in India. PMID- 29013450 TI - The Treatment of Hookworm Anaemia. PMID- 29013451 TI - Recovery of Spirillum Minus from the Peripheral Blood of a Rat-Bite Fever Case by Experimental Inoculation into a Clean Mouse. PMID- 29013452 TI - Sedimentation Rate of Red Blood Cells in Epidemic Dropsy. PMID- 29013453 TI - A Case of Dacryops. PMID- 29013454 TI - Biological Control of Culicine Mosquitoes, by Prawns in a Bengal Coal Mine. PMID- 29013456 TI - Incidence of Lead Poisoning among Hindu Women and Children. PMID- 29013455 TI - Chemotherapy in Plague. PMID- 29013457 TI - Thrombophlebitis of the Cavernous Sinus. PMID- 29013458 TI - Haematological Technique. Part VII. PMID- 29013459 TI - Current Topics. PMID- 29013460 TI - An Insectary Colony of A. Stephensi Mysorensis. PMID- 29013461 TI - Medical News. PMID- 29013462 TI - Surgical Complications of Filariasis. PMID- 29013463 TI - Spontaneous Pneumothorax with a Pleuro-Peritoneal Fistula. PMID- 29013464 TI - Urinary Excretion of Nicotinic Acid in Pellagrins. PMID- 29013465 TI - Lecture on Co-Ordinated Effort in Hygiene. PMID- 29013466 TI - Haematological Technique. Part X. PMID- 29013467 TI - The Sterility and Potency of Injectable Substances: (ii) Salines for Intravenous Use. PMID- 29013468 TI - A Further Type of Choleraphage- Type N. PMID- 29013469 TI - Viper Venom in a Case of Recurrent Haemorrhage in the Vitreous. PMID- 29013471 TI - Service Notes. PMID- 29013470 TI - Reduction of Benedict's Solution by Urine during a Course of Sulphathiazole Therapy. PMID- 29013472 TI - Current Topics. PMID- 29013473 TI - A Report on the Use of Cadmium Sulphide in the Treatment of Pulmonary Tuberculosis at the Jadabpur Tuberculosis Hospital. PMID- 29013475 TI - Scorpion Sting in Human Beings. PMID- 29013474 TI - A Search for Latent Sylvatic Plague in Calcutta. PMID- 29013476 TI - 'Xiphisternal Ache' or Low Substernal Pain. PMID- 29013477 TI - The Use of Cassia Fistula in the Treatment of Black-Water Fever. PMID- 29013479 TI - A Case of Scarlet Fever. PMID- 29013478 TI - Erythrocyte Sedimentation Rate in Cholera. PMID- 29013481 TI - The Need for a Cheap and Efficient Anti-Malarial Drug in India. PMID- 29013480 TI - Treatment of a Case of Small-Pox with Sulphonamide-P. PMID- 29013482 TI - Abstracts from Reports. PMID- 29013483 TI - Fracture of the Carpal Scaphoid. PMID- 29013484 TI - Water in Relation to Health. PMID- 29013485 TI - Service Notes. PMID- 29013486 TI - Annual Report of the Public Health Commissioner with the Government of India for the Year 1940. PMID- 29013487 TI - Reorganization of the Medical and Allied Services in Great Britain. PMID- 29013488 TI - A Method for Ascertaining the Overlapping of the Pubis by the Head by Means of Abdominal Examination Alone. PMID- 29013489 TI - Medical News. PMID- 29013490 TI - Trichostrongylus Infection in Man. PMID- 29013491 TI - Haematological Technique: Part XIV. PMID- 29013492 TI - Bengal Public Health Report for the Year 1939. By Lieut.-Colonel A. C. Chatterji, M.B., D.P.H., I.M.S., Director of Public Health. PMID- 29013493 TI - Current Topics. PMID- 29013494 TI - Course of Public Health Events. PMID- 29013495 TI - An Encephalocele. PMID- 29013496 TI - Endemic Typhus in Mysore. PMID- 29013497 TI - Blackwater Fever in Darjeeling-Terai. PMID- 29013499 TI - Abstracts from Reports. PMID- 29013498 TI - Sulphanilylguanidine in Cholera. PMID- 29013500 TI - A Preliminary Survey of the Industrial Hygiene Problem in the United States. Public Health Bulletin No. 259, United States Government Printing Office, Washington, 1940. PMID- 29013501 TI - Developmental Anomalies of Kidney and Ureter. PMID- 29013502 TI - Dystocias Due to Anomalies of the Foetus Associated with Dilatation of the Foetal Urinary Bladder. PMID- 29013503 TI - The Prevailing Types of Pneumococci in Pneumonia and Pneumococcal Infections. PMID- 29013504 TI - Russell's Viper Venom in Threatened Miscarriage. PMID- 29013505 TI - Ocular Manifestations Due to Lack of Vitamin ' A ' in the System : With Special Reference to the Treatment in General Practice. PMID- 29013506 TI - Report on the Public Health Administration of the City of Rangoon, for the Year 1940. PMID- 29013507 TI - Leucoderma. PMID- 29013509 TI - Post-Sulphapyridine Anuria: With a Case Report. PMID- 29013508 TI - Arsenic in Food. PMID- 29013510 TI - A Method of Oiling Streams and Drains by an Automatic Drip System. PMID- 29013512 TI - The Evolution of Blood Transfusion and the Present Emergency. PMID- 29013511 TI - Combined Digitalis and Rauwolfia Poisoning in a Human Subject. PMID- 29013513 TI - Report on the Working of the Harcourt Butler Institute of Public Health, Rangoon, for the Year 1940. PMID- 29013514 TI - Detection of Arsenic in Burnt Human Bones and Ashes. PMID- 29013515 TI - Stains Other Than Blood-Stains as Medico-Legal Evidence. PMID- 29013516 TI - On the Choice of Drugs in the Treatment of Bacterial Infections. PMID- 29013517 TI - A Case of Enteric Pneumatosis. PMID- 29013518 TI - A Case of Snake Bite Successfully Treated with the Help of the 'Iron Lung'. PMID- 29013519 TI - The Effect of Stocking Rice Fields with Sullage at Khurda Road on Anopheline Breeding. PMID- 29013520 TI - A Cheap Flush-Out Latrine. PMID- 29013521 TI - Medical News. PMID- 29013522 TI - Cerebral Malaria Simulating Meningitis. PMID- 29013523 TI - A Case of Plague Successfully Treated with Sulphapyridine. PMID- 29013524 TI - Kaposi's Disease. PMID- 29013525 TI - Service Notes. PMID- 29013526 TI - The Presence of an Enzootic of Rickettsial Infection in Wild Rats of Calcutta. PMID- 29013527 TI - Sulphathiazole in Some Experimental Bacterial and Virus Infections. PMID- 29013528 TI - Two Fatal Cases of Cardiac Malaria. PMID- 29013529 TI - Erythema Standard for Dose in Light. PMID- 29013530 TI - A Case of Yaws. PMID- 29013531 TI - Pseudo-Pancreatic Cyst in a Malarial Subject. PMID- 29013532 TI - Treatment of Gonorrhoea with M.&B. 693: 75 Patients. PMID- 29013533 TI - Indian Hospital Unit in London. PMID- 29013534 TI - Treatment of Tuberculosis Verrucosa Cutis by Local Application of Creosote and Salicylic Acid. PMID- 29013535 TI - Hydatid Cyst in the Transverse Mesocolon. PMID- 29013536 TI - Pre-Auricular Fistulae. PMID- 29013537 TI - A Case of Gonococcal Vulvo-Vaginitis Treated with M.&B. 693. PMID- 29013538 TI - Haematological Technique. Part VIII. PMID- 29013539 TI - Thyroid Drugging in Graves' Disease. PMID- 29013540 TI - Goitre. PMID- 29013541 TI - Clinical Observations on Landry's Paralysis (Based on a Study of 10 Cases). PMID- 29013542 TI - A Simple Method of Obtaining Anaerobiosis. PMID- 29013543 TI - Current Topics. PMID- 29013545 TI - Current Topics. PMID- 29013544 TI - Ages of Epiphysial Union at Elbow and Wrist Joints Amongst 238 Children in North West Frontier Province. PMID- 29013546 TI - Haematological Technique. PMID- 29013547 TI - The Treatment of Burns. PMID- 29013548 TI - Tuberculosis of the Female Genital Tract. PMID- 29013550 TI - A Case of Dystrophia Adiposo-Genitalis. PMID- 29013551 TI - The Sterility of Snake Venom Solutions. PMID- 29013549 TI - Notes on Common Skin Diseases II. Ringworm of the Scalp. PMID- 29013553 TI - Medical News. PMID- 29013552 TI - Dactylomegaly: A Case Note. PMID- 29013554 TI - Service Notes. PMID- 29013555 TI - Abstracts from Reports. PMID- 29013556 TI - Maintenance of Bacterial Cultures. PMID- 29013558 TI - Antiseptic Analgesic Tannic-Acid Jelly for Burns. PMID- 29013557 TI - A Case of Acute Thrombocytopenic Purpura. PMID- 29013559 TI - Cachexia Hypophysio-Priva (Simmonds' Disease). (Describing a Case Cured under Treatment). PMID- 29013560 TI - Laboratory Procedures, Apparatus and Improvizations. PMID- 29013561 TI - School Medical Inspections. PMID- 29013562 TI - On the Composition of Buffalo Milk and the Detection of Adulterated Samples Passed as Cow Milk. PMID- 29013563 TI - Non-Specific Ulcers of the Alimentary Tract. PMID- 29013564 TI - Haematological Technique. Part XI. PMID- 29013565 TI - Recovery from Pneumococcal Meningitis Treated with M. & B. 693. PMID- 29013566 TI - Scars and Opacities of the Cornea and Their Treatment. PMID- 29013567 TI - Lesser Knowledge of Human Tubercle Bacillus: Serological Affinity with Allergic States, Variation in Content, etc. PMID- 29013568 TI - A Note on Complement-Fixation Test in Leprosy and Kala-Azar with Witebsky, Klingenstein and Kuhn (W.K.K.) Antigen. PMID- 29013569 TI - Transillumination and Simultaneous Cauterization of Pleural Adhesions. PMID- 29013570 TI - Pneumo-Peritoneum in the Treatment of Advanced Pulmonary Tuberculosis. PMID- 29013572 TI - Congenital Malaria. PMID- 29013571 TI - Nursery School and Parent Education in Soviet Russia: A Review. PMID- 29013573 TI - A Case of Ether Convulsions. PMID- 29013574 TI - Erratum: Materia Medica of Pharmaceutical Combinations and Specialities. AB - [This corrects the article on p. 440b in vol. 76.]. PMID- 29013576 TI - The Formation, Evolution, and Healing of Tuberculous Cavities in the Lungs. PMID- 29013575 TI - Certain Epidemiological Aspects of Pulmonary Tuberculosis in Northern India. PMID- 29013577 TI - Bone and Joint Tuberculosis: A Review of 175 Cases. PMID- 29013578 TI - Tuberculosis as a Public Health Problem in India. PMID- 29013579 TI - A Case of Imperforate External Urinary Meatus. PMID- 29013580 TI - Medical News. PMID- 29013581 TI - Recent Advances in Our Knowledge about Vitamin B1. PMID- 29013582 TI - Service Notes. PMID- 29013583 TI - The Importance of a Standard in Examination for Tubercle Bacilli. PMID- 29013584 TI - Bored-Hole Absorption Pits. PMID- 29013585 TI - Viper Venom in a Case of Recurrent Haemorrhage in the Vitreous. PMID- 29013587 TI - Extra-Pleural Pneumothorax-Its Scope and Limitations. PMID- 29013586 TI - A Municipal Scheme for Tuberculosis Control. PMID- 29013588 TI - The Incidence of Bacterium AErogenes in the Faeces of Persons Suffering from Intestinal Infections and Its Significance in Water Analysis. PMID- 29013589 TI - Thoracoscopy and Pneumolysis in Tuberculosis. PMID- 29013590 TI - Current Topics. PMID- 29013591 TI - The Special Tuberculosis Number. PMID- 29013592 TI - Public Health Aspects of Enriched Flour and Bread. A Report of an Address. PMID- 29013593 TI - Abstracts from Reports. PMID- 29013594 TI - Gas Replacement in Pleural Effusions. PMID- 29013595 TI - A Case of Abdominal Pregnancy and Delivery per Rectum. PMID- 29013596 TI - The Sterility and Potency of Injectable Substances: (iii) Cholera Vaccines. PMID- 29013597 TI - Vesical Calculus in a Vaginal Cystocoele. PMID- 29013598 TI - Medical Practitioners and Medical Relief at the Moghul Court during the Reign of Akbar the Great. PMID- 29013599 TI - Brucella Infection in Vizagapatam. PMID- 29013600 TI - Service Notes. PMID- 29013601 TI - Plasma Transfusion. PMID- 29013602 TI - Hypochloraemia in Cholera. PMID- 29013603 TI - Current Topics. PMID- 29013604 TI - Treatment of Scabies and Pediculosis with Pyrethrum. PMID- 29013605 TI - Medical News. PMID- 29013606 TI - A Case of Eclampsia. PMID- 29013607 TI - Treatment of Fractures of the Leg. PMID- 29013608 TI - Erythropoietic Factor in Human Mixed Saliva. PMID- 29013610 TI - Abstracts from Reports. PMID- 29013609 TI - A Rare Case of Dermatalgia. PMID- 29013611 TI - Notes on an Epidemic of Influenza. PMID- 29013612 TI - Interstitial Keratitis Due to Focal Sepsis. PMID- 29013613 TI - Prothrombin Time in Health and Disease. (According to Quick's Method). PMID- 29013614 TI - Erratum: Tuberculosis of the Female Genital Tract. AB - [This corrects the article on p. 257 in vol. 76.]. PMID- 29013615 TI - A Study of Rhinoscleroma in Vizagapatam. PMID- 29013616 TI - Some Observations on Enteric Fevers. PMID- 29013618 TI - A Note on the Treatment of Relapsing Malaria. PMID- 29013619 TI - Induced Malaria with Heavy Malignant Tertian Infection. PMID- 29013617 TI - The Significance of the Takata-Ara Reaction in the Diagnosis and Prognosis of Hepatic Cirrhosis. PMID- 29013620 TI - Toxic Complications of Sulphanilamide Therapy. (An Analysis of 6,070 Cases Treated in the Venereal Department of the Government General Hospital, Madras). PMID- 29013621 TI - A Mobile Appendical Abscess. PMID- 29013622 TI - Itching in Syphilitic Skin Eruptions. PMID- 29013623 TI - Trichophyton Crateriforme in India. PMID- 29013624 TI - Cases of Poisoning and Suspected Poisoning. Lecture Given to the Lahore Branch of the British Medical Association. PMID- 29013626 TI - Service Notes. PMID- 29013625 TI - Ideal Marriage. PMID- 29013627 TI - Medical News. PMID- 29013629 TI - Hours of Work. PMID- 29013628 TI - Omental Lipoma. PMID- 29013630 TI - Taking Blood for Transfusion : Further Improvisations. PMID- 29013631 TI - Blackwater Fever in the Hills. PMID- 29013632 TI - Haematological Technique Part XII. PMID- 29013633 TI - Abstracts from Reports. PMID- 29013634 TI - A Note on Complement Fixation in Hydatid Disease and Associated Considerations. PMID- 29013635 TI - A Case of Cavernous Sinus Thrombosis Complicating Meningococcal Meningitis with Recovery. PMID- 29013636 TI - A Case of Cerebral Malaria with Rare Complications and Complete Recovery. PMID- 29013637 TI - The Arneth Count in Normal Indians. PMID- 29013638 TI - Pathogenesis of Bronchiectasis. PMID- 29013639 TI - A Study of Cardiac Sounds and Murmurs in Severe Anaemia. PMID- 29013640 TI - A Note on Fevers of the Typhus Group in Assam. PMID- 29013641 TI - A Thoracopagus Monster. PMID- 29013642 TI - Multiple Primary Epidermoid Carcinoma. PMID- 29013644 TI - Current Topics. PMID- 29013643 TI - A Case of Leucopenia within Twenty-Four Hours of the Initial Administration of Para-Sulphanilyl-Aminopyridine. PMID- 29013645 TI - Notes on Common Skin Diseases. III. Ringworm of the Scalp : Favus. PMID- 29013646 TI - Perforation of a Meckel's Diverticulum with Gastric Mucosa. PMID- 29013647 TI - The Arneth Count in Normal Indians. PMID- 29013648 TI - A Case of Pyaemia Treated with Sulphathiazole. PMID- 29013649 TI - Bact. Alkalescens in Infection of the Urinary Tract and Bacteriophage Therapy. PMID- 29013650 TI - Bacteriophages in Soil. PMID- 29013652 TI - An Unusual Case of Proteinuria. PMID- 29013651 TI - Rural Medical Relief. PMID- 29013653 TI - Pneumococcal Peritonitis: With Report of a Recovery with M. & B. 693. PMID- 29013654 TI - The Enumeration of the Blind in India. PMID- 29013655 TI - Medical News. PMID- 29013656 TI - Pneumococcal Peritonitis. PMID- 29013657 TI - On a Plasmodium SP. of the Malay Chestnut-Bellied Munia [Munia Atricapilla Atricapilla (Vieill.)]. PMID- 29013658 TI - Notes on Common Skin Diseases: I. Ringworm of the Foot. PMID- 29013659 TI - Vitamin A and Carotene Reserves in Human Livers. PMID- 29013661 TI - Current Topics. PMID- 29013660 TI - Diphtheria: Difficulties in the Morphological Diagnosis of Corynebacterium Diphtheriae. PMID- 29013662 TI - On a Trypanosome of the White-Throated Munia-Uroloncha Malabarica (Linn.). PMID- 29013663 TI - Kangri-Burn Cancer. PMID- 29013664 TI - Cerebral Malaria-An Afebrile Case with Epileptiform Convulsions. PMID- 29013665 TI - Chemotherapy in the Treatment of Cerebrospinal Meningitis. PMID- 29013666 TI - Non-Specific Inflammation of the Lung. PMID- 29013667 TI - The Use of Bacteriophage for Freeing Protozoal Cultures of Contaminating Bacteria: Isolation of Leptospira Icterohoemorrhagiae from a Mixed Infection in Guinea-Pigs. PMID- 29013669 TI - Hookworm Infection. PMID- 29013668 TI - The Sterility and Potency of Injectable Substances: (i) Glucose Solutions. PMID- 29013670 TI - Yellow Fever. PMID- 29013671 TI - A Preliminary Study of Plague at a Hill Station in the Nilgiris, South India. PMID- 29013672 TI - Unofficial Qualifications. PMID- 29013673 TI - A Case of Malarial Psychosis. PMID- 29013674 TI - Abstracts from Reports. PMID- 29013675 TI - A Case of Duplication of the Genital Tract. PMID- 29013677 TI - Service Notes. PMID- 29013676 TI - Haematological Technique: Part IX. PMID- 29013678 TI - Rural Malaria. PMID- 29013679 TI - Some Social Obstacles to Malaria Control. PMID- 29013680 TI - A Note on the Occurrence of Leptospirosis in Bombay. PMID- 29013681 TI - Glaucoma. PMID- 29013682 TI - The Biochemical Standardization Laboratory. PMID- 29013683 TI - Service Notes. PMID- 29013685 TI - Granulomatous Ulcers of Small Intestine Causing Annular Stricture and Intestinal Obstruction. PMID- 29013684 TI - Insulin Requirements in India. PMID- 29013686 TI - Plaster of Paris in the Treatment of Wounds and Fractures. PMID- 29013688 TI - Medical News. PMID- 29013687 TI - A Transfusion Set for Use in Hospitals or in the Field. PMID- 29013689 TI - Current Topics. PMID- 29013690 TI - A Case of Tetanus Treated with Serum and Magnesium Sulphate. PMID- 29013691 TI - Plaster of Paris. PMID- 29013692 TI - Anti-Malarial Operations in India. PMID- 29013693 TI - Leptospiral Jaundice in Assam. PMID- 29013694 TI - Abstracts from Reports. PMID- 29013695 TI - A Case of Twin Pregnancy-One Uterine and the Other Extra-Uterine. PMID- 29013696 TI - Malaria Specifics. PMID- 29013699 TI - Haematological Technique. Part XIII. PMID- 29013697 TI - Successful Administration of Sulphanilamide to an Infant. PMID- 29013698 TI - Ephedrine Poisoning in a Human Subject. PMID- 29013700 TI - Head Injury and Its Management. PMID- 29013701 TI - Observations on the Naked-Eye Manifestations of Chronic Infective Processes in the Abdomen. PMID- 29013702 TI - Erratum: The Formation, Evolution, and Healing of Tuberculous Cavities in the Lungs. AB - [This corrects the article on p. 592 in vol. 76.]. PMID- 29013704 TI - Bacteriophage and Water Contamination. PMID- 29013703 TI - Insulin Requirements in India. PMID- 29013705 TI - Physiological Hygiene. PMID- 29013706 TI - An Interesting Case of Malaria. PMID- 29013707 TI - Practical Aspects on General Anasarca, Especially in Malarial Nephritis and Hookworm Disease. PMID- 29013708 TI - The Benzidine Reaction of Blood Simulated by a Clay (Bentonite). PMID- 29013709 TI - Notes on Common Skin Diseases. IV. Leucoderma. PMID- 29013710 TI - Studies on Leptospira Icterohaemorrhagiae in Rats in Bombay City. PMID- 29013711 TI - Abstracts from Reports.